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  • Immunocytochemistry  (70)
  • hypertension  (59)
  • Drosophila  (47)
  • Coleoptera  (44)
  • Springer  (220)
  • Annual Reviews
  • Blackwell Publishing Ltd
  • Massachusetts Institute of Technology and Woods Hole Oceanographic Institution
  • 2020-2024
  • 2005-2009
  • 1990-1994
  • 1980-1984  (220)
  • 2009
  • 1984  (117)
  • 1982  (103)
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  • 2020-2024
  • 2005-2009
  • 1990-1994
  • 1980-1984  (220)
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  • 1
    ISSN: 1570-7458
    Keywords: Pterostichus melanarius ; Coleoptera ; Carabidae ; pitfall traps ; insecticides ; prey ; hunger ; activity ; Rhopalosiphum padi ; Fenitrothion ; Sumicidin (Fenvalerate) ; spring barley
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé Au cours d'essais à grande échelle, effectués en 1981 et 1982, sur orge de printemps, pour évaleur l'effet des insecticides Fenitrothion et Sumicidine (fenvalerate) sur les arthropodes utiles, un accroissement significatif des captures, dans des trappes pièges de Barber, de Pterostichus melanarius (Illiger) a été observé plusierus semaines après le traitement dans les lots traités par rapport aux lots témoins. Significativement plus de femelles de P. melanarius ont été capturées dans les parcelles traitées pendant cette période d'accroissement après traitement. Une diminution correspondante dans les populations de proies a été observée à la suite des traitements. Chaque femelle de P. melanarius des parcelles traitées avait une fraction significativement moins importance de son intestin remplie d'aliments solides (arthropodes) que celles des parcelles non traitées. Des auteurs précédents avaient observé des taux de capture plus rapides dans les trappes et ne plus grande mobilité des carabes affamés. La réduction des populations proies par l'application d'insecticides affamerait les carabes dont l'activité serait par suite plus élevée. Comme le taux de captures dans les trappes est dû à la fois à la taille de la population et à son activité, on en déduit que la capture par trappes seule ne peut donner une image exacte de l'effet des insecticides sur les populations de carabes dans les champs.
    Notes: Abstract During large-scale field experiments in 1981 and 1982, designed to assess the effects of the insecticides Fenitrothion and Sumicidin (Fenvalerate) on beneficial arthropods in spring barley, significant increases in pitfall-trap catches of Pterostichus melanarius (Illiger) were observed in treated plots compared to untreated controls, several weeks after treatment. Significantly more female P. melanarius were caught in treated plots during these post-treatment increases. Corresponding decreases were observed in prey populations following treatments. Individual female P. melanarius from treated plots had significantly fewer of their gut areas full of solid (arthropod) food when compared to those from untreated control plots. Earlier workers observed both faster recapture rates in pitfalls and higher mobility in hungry carabid beetles. The following hypothesis is suggested: reducing prey populations by the application of insecticides results in hungrier carabid beetles with consequently higher activity. Since pitfall-trap catch is determined not only by population size but also activity, it is argued that pitfall-trap catches alone cannot give a true measure of the effects of insecticides on carabid populations in the field.
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  • 2
    ISSN: 1570-7458
    Keywords: Coleoptera ; Curculionidae ; Cylas formicarius elegantulus ; sweetpotato weevil ; sweet potato ; digestion ; enzyme distribution ; trypsin-inhibitors ; resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé L'activité endoprotéinase était limitée au liquide de la lumière des régions ventriculaires antérieure et postérieure de l'intestin moyen des larves deCylas formicarius elegantulus Summers. Les aminopeptidases ont été trouvées dans le liquide de la lumière (18%), mais étaient principalement associées avec les fractions insolubles des cellules du ventricule postérieur (82%). Suivant le substrat, l'activité carboxypeptidase était à peu près également répartie entre le liquide de la lumière et les fractions insolubles des cellules du ventricule postérieur. L'amylase, enzyme secrétée, a été observée à la fois dans la lumière antérieure et postérieure. Cinq bandes d'activité amylase ont été révélées sur zymogrammes d'amidon après électrophorèse d'intestins moyens entiers. Trois des bandes d'amylase pouvaient provenir de la plante. Il y avait au moins 2 α-glucosidases, une secrétée et une liée aux cellules du ventricule antérieur. L'activite β-glucosidase était liée aux cellules du ventricule antérieur, fandis que l'activité α-galactosidase était limitée au fluide de la lumière. Les activités β-galactosidase et cellulase ont été trouvées à la fois dans le liquide de la lumière et dans la fraction cellulaire insoluble. Ainsi, la digestion initiale des grosses protéines et des polymères de carbohydrates se produit dans le liquide de la lumière dans les régions ventriculaires antérieure et postérieure. Cependant, l'achèvement de la digestion des oligopeptides se produit principalement dans le ventricule postérieur, tandis que la fin de la digestion des oligosaccharides se produit dans le ventricule antérieur. Les concentrations en inhibiteurs de trypsine de 5 cultivars d'I. batatas L. diffèrent de 1 à 20. Les endoprotéinases deC. formicarius elegantulus ont été inhibées par des extraits de cultivars, mais les cultivars avec des concentrations relativement élevées d'inhibiteur avainent antérieurement montré être susceptibles d'être attaqués par le coléoptère dans des essais en champs.
    Notes: Abstract Endoproteinase activity was confined to luminal fluid from anterior and posterior ventricular regions of midguts of larvae of the sweetpotato weevil,Cylas formicarius elegantulus (Summers). Aminopeptidase was found in luminal fluid (18%) but was primarily associated with insoluble fractions from cells of the posterior ventriculus (82%). Depending on substrate, carboxypeptidase activity was about equally distributed between luminal fluid and insoluble fractions from posterior ventriculus cells. Amylase was found in luminal fluid in both the anterior and posterior ventriculus. Five bands of amylase activity were detected on starch zymograms following electrophoresis of whole midgut samples. Three of the amylase bands may be plant-derived. At least two α-glucosidases were present, one secreted and one bound to anterior ventriculus cells. β-Glucosidase activity was bound to anterior ventriculus cells whereas α-galactosidase activity was confined to luminal fluid. β-Galactosidase and cellulase activities were found in both luminal fluid and the insoluble cell fraction. Thus, initial digestion of large protein and carbohydrate polymers occurs in luminal fluid in both anterior and posterior ventriculus regions. However, terminal digestion of oligopeptides occurs primarily in the posterior ventriculus while terminal digestion of oligosaccharides occurs in the anterior ventriculus. A 20-fold difference in trypsin-inhibitor concentration was found among five sweetpotato cultivars. Endoproteinases from sweetpotato weevil larvae were inhibited by extracts from the cultivars but cultivars with relatively high concentrations of inhibitor were previously shown to be susceptible to weevil attack in field trials.
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  • 3
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    Journal of molecular evolution 18 (1982), S. 310-314 
    ISSN: 1432-1432
    Keywords: Neutral mutation theory ; Natural selection ; Protein evolution ; Levene model ; Environmental variability ; Genetic variability ; Drosophila
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary If a phenotypic character is under stabilizing selection, the selective disadvantage of a nonoptimal genotype will decrease exponentially to zero as the proportion of phenotypic variation that is environmental in origin -V e /V p - increases. Under the modified mutation-drift hypothesis of genetic polymorphism, the proportion of mutations that are effectively neutral and average heterozygosity should increase with this ratio. Invertebrates, because of their small size, fast development, and low degree of homeostasis (relative to vertebrates), are expected to show a larger environmental component of phenotypic variation than vertebrates. This may help explain why invertebrates are in general more genetically variable than vertebrates and why, when laboratory populations ofDrosophila are maintained in heterogeneous environments, genetic variability is lost less rapidly than when they are kept in constant conditions.
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  • 4
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    Journal of molecular evolution 20 (1984), S. 251-264 
    ISSN: 1432-1432
    Keywords: Drosophila ; Genome evolution ; 68C Glue gene cluster ; Drosophila melanogaster species subgroup
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The 68C puff is a highly transcribed region of theDrosophila melanogaster salivary gland polytene chromosomes. Three different classes of messenger RNA originate in a 5000-bp region in the puff; each class is translated to one of the salivary gland glue proteins sgs-3, sgs-7, or sgs-8. These messenger RNA classes are coordinately controlled, with each RNA appearing in the third larval instar and disappearing at the time of puparium formation. Their disappearance is initiated by the action of the steroid hormone ecdysterone. In the work reported here, we studied evolution of this hormone-regulated gene cluster in themelanogaster species subgroup ofDrosophila. Genome blot hybridization experiments showed that five other species of this subgroup have DNA sequences that hybridize toD. melanogaster 68C sequences, and that these sequences are divided into a highly conserved region, which does not contain the glue genes, and an extraordinarily diverged region, which does. Molecular cloning of this DNA fromD. simulans, D. erecta, D. yakuba, andD. teissieri confirmed the division of the region into a slowly and a rapidly evolving protion, and also showed that the rapidly evolving region of each species codes for third instar larval salivary gland RNAs homologous to theD. melanogaster glue mRNAs. The highly conserved region is at least 13,000 bp long, and is not known to code for any RNAs.
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  • 5
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    Development genes and evolution 193 (1984), S. 267-282 
    ISSN: 1432-041X
    Keywords: Drosophila ; Larval cuticle ; Pattern formation ; Embryonic lethal mutations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary In a search for embryonic lethal mutants on the second chromosome ofDrosophila melanogaster, 5764 balanced lines isogenic for an ethyl methane sulfonate (EMS)-treatedcn bw sp chromosome were established. Of these lines, 4217 carried one or more newly induced lethal mutations corresponding to a total of 7600 lethal hits. Eggs were collected from lethal-bearing lines and unhatched embryos from the lines in which 25% or more of the embryos did not hatch (2843 lines) were dechorionated, fixed, cleared and scored under the compound microscope for abnormalities of the larval cuticle. A total of 272 mutants were isolated with phenotypes unequivocally distinguishable from wild-type embryos on the basis of the cuticular pattern. In complementation tests performed between mutants with similar phenotype, 48 loci were identified by more than one allele, the average being 5.4 alleles per locus. Complementation of all other mutants was shown by 13 mutants. Members of the complementation groups were mapped by recombination analysis. No clustering of loci with similar phenotypes was apparent. From the distribution of the allele frequencies and the rate of discovery of new loci, it was estimated that the 61 loci represent the majority of embryonic lethal loci on the second chromosome yielding phenotypes recognizable in the larval cuticle.
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  • 6
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    Development genes and evolution 193 (1984), S. 90-97 
    ISSN: 1432-041X
    Keywords: Drosophila ; Temperature-sensitive ; Neoplasms ; Differentiation ; Imaginal discs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary EMS induced temperature-sensitivelethal (2) giant larva, 1(2)gl, alleles were isolated by screening against a knownl(2)gl allele. Analysis of the lethal phase of thel(2)gl ts-deficiency heterozygotes demonstrated: (1) the majority of thel(2)gl tslarvae survive to late third instar, (2) at 29°C the majority of thel(2)gl tslarvae failed to pupate and only rarely did they differentiate adult cuticular structures, (3) at 15°C the majority of the larvae pupated and frequently differentiated adult cuticular structures. Examination of the imaginal discs ofl(2)gl tslarvae reared at 29°C revealed the presence of morphologically abnormal wing, haltere and leg imaginal discs. No morphologically abnormal discs were found in thel(2)gl tslarvae reared at 15°C. Studies on both the histology and the developmental capacity of the morphologically normal and abnormall(2)gl tsdiscs were performed. The morphologically normal discs are histologically normal and produce a full complement of adult cuticular structures. However, the morphologically abnormal discs contained both regions that maintained the normal monolayer epithelium and regions that had lost the normal tissue architecture. The implants obtained when the morphologically abnormal discs are injected into metamorphosing larvae contained only a limited number of the normal complement of adult structures and usually only structures found in the ventral wing hinge region were recovered. In addition, the “metamorphosed” morphologically abnormal discs contained undifferentiated tissue that gave rise to transplantable neoplasms when cultured in adults. The results of the studies on the pathology of thel(2)gl tslarvae are discussed with respect to the role of thel(2)gl tsfunction during normal development, the autonomy of the neoplastic development of thel(2)gl tstissues, and similarities between neoplastic development inDrosophila and mammals.
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  • 7
    ISSN: 1432-041X
    Keywords: Drosophila ; Pole cell transplantation ; Heterospecific combinations ; Gametogenesis ; Chorion morphology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary We transplanted pole cells betweenDrosophila melanogaster, D. mauritiana andD. ananassae to investigate the ability of germ cells to develop in the gonad of a heterospecific host, and to study the interaction between somatic follicle cells and the cells of the germ line in producing the species-specific chorion. FemaleD. mauritiana germ cells in aD. melanogaster ovary produced functional eggs with normal development potential. The same is true for the reciprocal combination. FemaleD. ananassae pole cells in aD. melanogaster host only developed to a very early stage and degenerated afterwards. None of the interspecific combinations of male pole cells led to functional sperm. We could not determine at what stage the transplanted male pole cells were arrested. The cooperation of follicle cells and the oocyte-nurse cell complex in producing the chorion was studied using the germ-line-dependent mutationfs(1) K10 ofD. melanogaster, which causes fused respiratory appendages and an abnormal chorion morphology. Wild-type femaleD. mauritiana germ cells in a mutantfs(1) K10 D. melanogaster ovary led to the production of wild-type eggs withD. melanogaster-specific, short respiratory appendages. On the other hand,D. melanogaster fs(1) K10 germ cells in aD. mauritiana ovary induced the formation of eggs with mutant fused appendages which were, however, typicallyD. mauritiana in length. When.D. mauritiana pole cells developed in aD. melanogaster ovary, the chorion exhibited a new imprint pattern that differs from both species-specific patterns.
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  • 8
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    Development genes and evolution 191 (1982), S. 285-288 
    ISSN: 1432-041X
    Keywords: Drosophila ; Imaginal discs ; homoeosis ; Compartments ; Aldehyde oxidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The aldehyde oxidase staining pattern in wing discs ofDrosophila melanogaster bearing the genotypesap blt /ap blt andap blt andap blt /ap 73n showns changes from the wild-type pattern. Extensive areas of the presumptive dorsal posterior wing blade, which are normally unstained, have enzyme activity in these mutants. In wings of these genotypes, dorsal posterior structures are replaced by dorsal anterior wing structures. A strong correlation has been found between the frequencies of various staining patterns in the discs and the extent of transformation in the cuticular structures of the wing, which is consistent with the idea that aldehyde oxidase activity can be used as an indicator in the wing disc of this transformation. Unlike the homoeotic mutationengrailed, apterous has not been interpreted as a selector gene yet the work reported here shows thatapterous alleles can cause changes resembling those of theengrailed phenotype both in aldehyde oxidase staining behaviour and in the cuticular transformation.
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  • 9
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    Development genes and evolution 191 (1982), S. 264-269 
    ISSN: 1432-041X
    Keywords: Drosophila ; Sexcombless ; Foreleg basitarsus ; Genital disc
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The chromosome which carries the mutationsexcombless (In(1)sx) affects males and females ofD. melanogaster. In the male foreleg basitarsi the number of sexcomb teeth is dramatically reduced from 10 to 0.7 and the number of transverse rows of bristles is increased from 6 to 8. Females homozygous forIn(1)sx show a normal bristle pattern in the foreleg basitarsus. The genital disc derivatives of both male and femaleIn(1)sx flies are strongly affected. While the external genitalia show a duplicated or a reduced bristle pattern, the internal genitalia are mostly absent. However, the sexually dimorphic tergites and sternites of the abdomen remain unaffected. The male-specific effect on the basitarsus and the general effects on the genital disc derivatives are proposed to represent two different phenotypic effects ofIn(1)sx which may derive from mutations at different gene loci in the inverted chromosome.
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  • 10
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    Development genes and evolution 191 (1982), S. 289-291 
    ISSN: 1432-041X
    Keywords: Drosophila ; Imaginal discs ; Cell competition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Imaginal wing discs from late third-instar larvae were gammairradiated to induce clones of rapidly growingMinute − cells in a background of slowly growingMinute cells and culturedin vivo for periods up to 18 days. Clones in discs cultured for 16 to 18 days did not grow significantly larger than clones in uncultured controls, indicating that competition between populations of cells having potentially different mitotic rates does not occur in imaginal discs after their growth is completed.
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  • 11
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    Development genes and evolution 193 (1984), S. 98-107 
    ISSN: 1432-041X
    Keywords: Drosophila ; Neoplasms ; Promotion ; Regeneration ; Temperature-sensitive ; Imaginal discs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary In this paper we present an analysis of the behavior ofl(2)gl tsimaginal wing discs during culture in adult hosts. Thel(2)gl tslarvae reared at 29° C contain two types of wing discs, those that are morphologically normal and those that are abnormal. When discs of both types are cultured in adult hosts at 29° C, the restrictive temperature, they give rise to transplantable neoplastic tissue. However, when the 29° C reared discs are cultured at 15° C, the permissive temperature, the morphologically normal discs maintain their morphology, but the morphologically abnormal discs give rise to neoplasms. Thel(2)gl tslarvae reared at 15° C contain only morphologically normal discs. When these discs are cultured in adult hosts at 29° C they give rise to neoplasms, however if the discs are cultured at 15° C they maintain their normal morphology. These results demonstrate: (1) that all wing imaginal discs obtained from 29° C rearedl(2)gl tslarvae are competent to undergo neoplastic development, (2) the morphologically abnormal discs obtained from the 29° C rearedl(2)gl tslarvae are committed to neoplastic development, (3) the neoplastic development of the morphologically normal discs is temperature dependent, (4) once the neoplastic development of thel(2)gl tsdiscs has been initiated the process is not readily reversible. In addition, the ability ofl(2)gl tswing discs to perform epimorphic regulation was tested by amputating morphologically normal permissively rearedl(2)gl tswing discs and culturing both fragiments at the permissive temperature. Fragments of control wild-type discs maintained their morphology during culture at the permissive temperature. However, both fragments of txel(2)gl tsdiscs became neoplastic. This result is discussed with respect to a possible role for thel(2)gl +function in epimorphic regulation and with respect to the phenomena of tumor promotion in vertebrates.
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  • 12
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    Development genes and evolution 191 (1982), S. 103-111 
    ISSN: 1432-041X
    Keywords: Drosophila ; Polytene Chromosomes ; Ecdysteroids ; Fat Body
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Changes in polytene chromosome 3 L puffing patterns in the fat body ofDrosophila melanogaster larvae and prepupae are compared to those in the salivary gland. While some general features are common to the two tissues, there are differences which reflect their different developmental roles. In vitro experiments with fat body chromosomes show that they have a distinct response to ecdysteroids which is different from that of salivary gland chromosomes, and which does not,in this culture system, reproduce the changes observed in normal development. In short term culture experiments, the fat body chromosomes appear more sensitive to ecdysteroids than the salivary gland chromosomes and, although 20-OH ecdysone is more active than ecdysone in these assays, the possibility is not excluded that ecdysone has a role in normal development as it appears to alter gene activity at physiological levels in these cells.
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  • 13
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    Development genes and evolution 191 (1982), S. 293-300 
    ISSN: 1432-041X
    Keywords: Drosophila ; Imaginal discs ; Positional information ; Homology ; Intercalary regeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The regulative behavior of fragments of the imaginal discs of the wing and first leg was studied when these fragments were combined with fragments of other thoracic imaginal discs. A fragment of the wing disc which does not normally regenerate when cultured could be stimulated to regenerate by combination with certain fragments of the haltere disc. When combined with a haltere disc fragment thought to be homologous by the criteria of morphology and the pattern of homoeotic transformation, such stimulated intercalary regeneration was not observed. Combinations of first and second leg disc fragments showed that a lateral first leg fragment could be stimulated to regenerate medial structures when combined with a medial second leg disc fragment but not when combined with a lateral second leg disc fragment. Combinations of wing and second leg disc fragments showed that one fragment of the second leg disc is capable of stimulating regeneration from a wing disc fragment while another second leg disc fragment fails to stimulate such regeneration. It is suggested that absence of intercalary regeneration in combinations of fragments of different thoracic imaginal discs is a result of homology or identity of the positional information residing in the cells of the fragments. The pattern of correspondence of positional information revealed by this analysis is consistant with the pattern of homology determined by morphological observation and by analysis of the positional specificity of homoeotic transformation among serially homologous appendages. The implications of the existence of homologous positional information in wing and second leg discs which share a common cell lineage early in development are discussed.
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  • 14
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    Development genes and evolution 191 (1982), S. 335-339 
    ISSN: 1432-041X
    Keywords: Drosophila ; Gap junction ; Wing disc
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The distribution of gap junctions in mature larvalDrosophila melanogaster wing discs was analyzed by means of quantitative electron microscopy. Gap junctions are non-randomly distributed in the proximal-distal disc axis and in the apical-basal cell axis of the epithelium. In the epithelial cells, the surface density, number and length of gap junctions are greatest in the apical cell region and distal disc region. The average gap junction surface density is 0.0572 μm−1 and 2.77% of the lateral cell surface is composed of gap junctions. In the adepithelial cells, the gap junction surface density is 0.0005 μm−1 and 0.06% of the cell surface is composed of gap junctions. No gap junctions were observed between epithelial cells and adepithelial cells. The absolute area of gap junctions was estimated in a proximal-distal strip of cells in the disc and is considerably less in the folded regions of the epithelium compared to the flat notum and wing pouch regions. The results are discussed with respect to pattern formation and growth control in imaginal discs.
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  • 15
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    Development genes and evolution 191 (1982), S. 28-36 
    ISSN: 1432-041X
    Keywords: Drosophila ; Polarity ; Maternal effect ; Nurse cells ; Embryogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The mutationdicephalic (dic) affects follicle development and thereby alters the antero-posterior polarity of embryonic patterning. It maps at a single locus (3–46.0±1.0) and can be characterized as a semi-dominant maternal effect mutation with low penetrance. Indic follicles, the 15 nurse cells form two clusters located at opposite poles of the oocyte; the numerical distribution of the nurse cells among the clusters varies from 7:8 to 1:14. Thedic egg shell carries a micropyle (anterior marker) at either pole, but the misshapen respiratory appendages are restricted to one of the two poles in most eggs. The malformed eggs rarely yield larvae and these are always abnormal anteriorly and/or posteriorly. The segment pattern expressed in their cuticle may represent two anterior parts of opposite polarities (double head type), two posterior parts of opposite polarities (double abdomen type, rare) or show uniform polarity. Lability of organization at the cystocyte stage appears as the primary developmental defect of the mutant.
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  • 16
    ISSN: 1432-041X
    Keywords: Drosophila ; Gap junction ; Imaginal disc ; Pattern formation ; EM Stereology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Developmental changes in the distribution of gap junctions in early, mid and late third larval stage wing discs and in pupariation+6 h and pupariation+24 h stage wing discs fromDrosophila melanogaster were analyzed by quantitative electron microscopy. Gap junctions occur in all 12 intradisc regions examined in each of the five developmental stages. Their distribution is non-random and changes during development which suggests that they are developmentally regulated. The gap junctions are not static structures, rather they grow and regress during development. The changes tend to be gradual ones without sudden increases or decreases. Gap junctions continuously form and grow in size throughout the third larval stage and during the first 6 h following pupariation. Their surface density, number, percent of the lateral plasma membrane area, and absolute area as well as the lateral plasma membrane surface density all increase during this time. Between pupariation+ 6 h and pupariation+24 h all but one of these parameters decrease indicative of gap junctional breakdown. Gap junctions are most numerous and change least during development in the apical cell regions where intercellular contacts are close and stable. They change most in the basal cell regions where intercellular contacts tend to be looser and change during development. The most dramatic change is in the absolute area which increases by a factor of 23 between the early third larval stage and pupariation+24 h. At pupariation the rate of gap junction growth undergoes a transient increase before the phase of disassembly begins. Developmental changes in gap junction surface density are closely coupled with changes in the lateral plasma membrane surface density which suggests that these may be coregulated. Evidence from mutants suggests that when the number and density of gap junctions fail to increase in proportion to lateral plasma membrane growth, wing disc development will be abnormal. Our results support the idea that some minimum gap junction density is required for normal development and that this must increase as development proceeds. The results are consistent with the notion that gap junctions are involved in pattern formation and growth control and are discussed with respect to the acquisition of competence for metamorphosis, disc growth, disc morphogenesis and changes in the hormonal environment.
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  • 17
    ISSN: 1432-041X
    Keywords: Major haemolymph proteins ; Development ; Cuticle ; Immunocytochemistry ; Ceratitis capitata
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The developmental profile of the major haemolymph proteins (ceratitins) inCeratitis capitata was studied. Ceratitin concentration in the haemolymph decreases dramatically during the last days of pupal life, while the amounts of ceratitins in whole organism extracts remain unchanged. By electrophoretic, immunological and immunofluorescence techniques it was revealed that ceratitins are reabsorbed by the fat body and a fraction of them is deposited in the cuticle. The possible role of ceratitins is discussed.
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  • 18
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    Development genes and evolution 191 (1982), S. 42-55 
    ISSN: 1432-041X
    Keywords: Clonal analysis ; Growth ; Cell lineage ; Genital disc ; Drosophila
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary InDrosophila, the terminalia (i.e. internal and external analia and genitalia, except the gonads) are formed by the genital disc. Comparative studies suggested that this disc may have evolved through fusion of the imaginal primordia of the last 3 or 4 abdominal segments. The present report describes the clonal relationships within the complex genital disc. Genetically marked cell clones were induced in male and female embryos and larvae heterozygous for cell marker mutations. 1) Frequencies and sizes of clones suggest that the embryonic disc anlage consists of 14–17 precursor cells: 4–6 for the analia, some 7 for the male genitalia, and 3–4 for the female genitalia. These cells grow exponentially during larval development. 2) In both sexes, the clones were confined to either analia or genitalia, suggesting two separate cell lineages already established at blastoderm. 3) Internal and external genitalia remain in the same compartment at least up to 60 h (end of first instar). 4) A clonal restriction appeared around 84 h (mid second instar), separating a dorsal from a ventral part in the male genitalia. The ventral compartment comprises the ventral part of the lateral plate and clasper, hypandrium, and all internal genitalia. No such boundary was detected in the female. 5) In the female, analia and parovaria originate from the same precursors; another cell lineage forms eighth tergites, vaginal plates, oviduct, receptacle, and spermathecae. 6) In female analia, dorsal and ventral plate share common precursors at least up to 84 h. A medio-lateral boundary may appear at 84 h in the ventral anal plate. No clonal restriction was found in the male analia. 7) At all times, clones could cross between left and right sides of the symmetrical terminalia; they consistently did so via ventral structures. 8) The results are discussed in a phylogenetic context, and we propose that the clonal relations reflect the evolution of the complex genital disc.
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    Development genes and evolution 191 (1982), S. 191-201 
    ISSN: 1432-041X
    Keywords: Neurogenic mutants ; Maternal effects ; Drosophila
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The size of the neurogenic region ofDrosophila melanogaster is under the control of several genes of zygotic expression. Lack of function from any of those genes produces an increase of the size of the neurogenic region at the expense of the epidermal anlage. However, differences exist in the extent of neuralisation achieved by each of the genetic loci upon mutation. The present results show that in the case ofN andmam phenotype differences are due to different contributions of maternal gene expression. This could be shown by studying the phenotype which appeared in mutant embryos when the oocytes developed from homozygous mutant precursor cells. Clones of mutant cells were induced in the germ line of females heterozygous for the neurogenic mutationin trans over germ line dependent, dominant female sterile mutations. After removing maternal information the phenotype ofN andmam mutants became identical in both cases. Furthermore maternal information fromN + was found to be necessary for viability of the wildtype.
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    Development genes and evolution 191 (1982), S. 211-214 
    ISSN: 1432-041X
    Keywords: Drosophila ; Clonal analysis ; Sex determination
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    Topics: Biology
    Notes: Summary The mutationSxl f , located on the X-chromosome, is a sex-limited recessive lethal that specifically kills 2X; 2A flies while it does not affect X; 2A flies (Cline 1978). We have analyzed the role ofSxl f on sex determination by a clonal analysis of a new spontaneous allele,Sxl fLS . Female embryos and larvae heterozygous forSxl fLS were irradiated at different times of development to generate homozygousSxl fLS clones which were recognized by linked marker mutations. We have studied the phenotype of such clones on sexually dimorphic regions of the fly (foreleg basitarsus, 5th, 6th and 7th tergites, analia and external genitalia). Despite their female (2X; 2A) chromosomal constitution, clones homozygous forSxl fLS differentiated male structures. These results confirm and extend the preliminary report of Cline (1979). They show that the wildtype product ofSxl f is required for female development.
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  • 21
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    Development genes and evolution 193 (1984), S. 296-307 
    ISSN: 1432-041X
    Keywords: Drosophila ; Larval cuticle ; Pattern formation ; Embryonic lethal mutations
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    Topics: Biology
    Notes: Summary In order to identify X-chromosomal genes required inDrosophila for early patterning and morphogenesis, we examined embryos hemizygous for EMS-induced lethal mutations to determine which of those mutations cause gross morphological defects. Embryos from 2711 lethal lines, corresponding to 3255 lethal point mutations were studied. Only 21% caused death during embryogenesis and of these, only one-sixth, or 3% of the total lethals, were associated with defects visible in the final cuticle pattern. Of the 114 point mutants causing visible cuticle defects, 76 could be assigned to 14 complementation groups. An additional 25 mutations mapping to regions of the X-chromosome not covered by male fertile duplications were assigned to six complementation groups based on similarities of map position and phenotype. Thirteen mutations could not be assigned to complementation groups. All mutations allowed normal development through the cellular blastoderm stage, the first defects associated with the earliest acting loci being observed shortly after the onset of gastrulation. The phenotypes of the various loci range from alterations in segment pattern or early morphogenetic movements to defects in final pigmentation and denticle morphology. Cuticle preparations were also examined for 63 deletions spanning in total 74% of the X-chromosome, as well as for 8 deletions and point mutations derived in saturation mutagenesis screens of the fourth chromosome (Hochman 1976). With the exception of defects in head morphology and defects in cuticle differentiation, none of the hemizygous deletions showed phenotypes other than those predicted by point mutations known to lie in those regions. No deletion caused new or unknown alterations in gastrulation, segmentation or cuticle pattern.These results suggest that the number of genes required zygotically for normal embryonic patterning is small and that most, if not all such loci, are represented by point mutations in our collection.
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  • 22
    ISSN: 1432-041X
    Keywords: Drosophila ; Imaginal disc ; Morphogenesis ; Tissue culture
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    Topics: Biology
    Notes: Summary The thin region of the peripodial membrane is confined to the area overlying the distal anlagen in thoracic discs. During the early stages of evagination the peripodial membrane is greatly stretched, but does not rupture. The appendage then evaginates through the stalk, probably by means of a contraction of the peripodial membrane. The cells of the peripodial membrane of leg and wing discs persist and differentiate sheets of trichomes characteristic of the ventral and lateral thorax. This is discussed in relation to imaginal disc fate maps.
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  • 23
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    Development genes and evolution 193 (1984), S. 263-265 
    ISSN: 1432-041X
    Keywords: Drosophila ; Biothorax complex ; Prothoracic transformation
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    Topics: Biology
    Notes: Summary If, early in development, theUbx + gene is removed by mitotic recombination from cells of the meso-and metathoracic leg primordia, theseUbx − cells develop as in the posterior prothoracic leg. We show that this transformation, termedpostprothorax, is a discrete genetic function that is independent of other homeotic transformations such asbx, pbx orbxd, which also result from the inactivation of theUbx gene.
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  • 24
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    Development genes and evolution 193 (1984), S. 283-295 
    ISSN: 1432-041X
    Keywords: Drosophila ; Larval cuticle ; Pattern formation ; Embryonic lethal mutations
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    Topics: Biology
    Notes: Summary The present report describes the recovery and genetic characterization of mutant alleles at zygotic loci on the third chromosome ofDrosophila melanogaster which alter the morphology of the larval cuticle. We derived 12600 single lines from ethyl methane sulfonate (EMS)-treatedst e orrucuca chromosomes and assayed them for embryonic lethal mutations by estimating hatch rates of egg collections. About 7100 of these lines yielded at least a quarter of unhatched eggs and were then scored for embryonic phenotypes. Through microscopic examination of unhatched eggs 1772 lines corresponding to 24% of all lethal hits were classified as embryonic lethal. In 198 lines (2.7% of all lethal hits), mutant embryos showed distinct abnormalities of the larval cuticle. These embryonic visible mutants define 45 loci by complementation analysis. For 32 loci, more than one mutant allele was recovered, with an average of 5.8 alleles per locus. Complementation of all other mutants was shown by 13 mutants. The genes were localized on the genetic map by recombination analysis, as well as cytologically by complementation analysis with deficiencies. They appear to be randomly distributed along the chromosome. Allele frequencies and comparisons with deficiency phenotypes indicate that the 45 loci represent most, if not all, zygotic loci on the third chromosome, where lack of function recognizably affects the morphology of the larval cuticle.
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  • 25
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    Development genes and evolution 193 (1984), S. 308-325 
    ISSN: 1432-041X
    Keywords: Neurogenesis ; Pattern of neuroblasts ; Drosophila
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    Topics: Biology
    Notes: Summary This paper deals with morphological aspects of early neurogenesis inDrosophila, in particular with the segregation of neuroblasts from the neurogenic region of the ectoderm and the pattern formed by those wells within both the germ band and the procephalic lobe. The neurogenic ectoderm was found to contain neural precursors intermingled with epidermal precursors, extending from the midline up to the primordia of the tracheal tree along the germ band and laterodorsally in the procephalic lobe. Germ band neuroblasts segregate from the neurogenic ectoderm during a period of several hours according to characteristic spatial and temporal patterns. During the first half of the segregation process the pattern of germ band neuroblasts was found to be the same in different animals in both spatial arrangement and number of cells; this permitted the identification of individual neuroblasts from different embryos. Later in development several difficulties were encountered which precluded an exact description of the neuroblast pattern. The constitution of the neurogenic region is discussed in relation to the phenotype of mutants affecting neurogenesis.
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  • 26
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    Development genes and evolution 193 (1984), S. 388-393 
    ISSN: 1432-041X
    Keywords: Drosophila ; Oogenesis ; Ring canals ; Oocyte determination ; Polarity
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    Topics: Biology
    Notes: Summary The pattern of intercellular connections between germ line cells has been studied in follicles of the mutantdicephalic (dic), which possess nurse cell clusters at both poles. Staining of follicles with a fluorescent rhodamine conjugate of phalloidin reveals ring canals and cell membranes and thus allows us to reconstruct the spatial organization of the follicle. Each germ line cell can be identified by the pattern of cell-cell connections which reflect the mitotic history of individual cells in the 16-cell cluster. The results indicate that in both wild-type anddicephalic cystocyte clusters one of the two cells with four ring canals normally becomes the pro-oocyte. However, in some follicles (dicephalic and wild-type) oocytes were found with fewer or more than four ring canals. Indic follicles, one or several nurse cells may become disconnected from the other cells during oocyte growth at stage 9–10. Such disconnected cells cannot later on empty their cytoplasm into the oocyte. This, in turn, might be of consequence for the determination of axial polarity of the embryo.
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  • 27
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    Development genes and evolution 193 (1984), S. 406-413 
    ISSN: 1432-041X
    Keywords: Drosophila ; Imaginal disc ; Morphogenesis ; Tissue culture
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    Topics: Biology
    Notes: Summary The fusion of the eye-antennal discs during culturein vitro has been investigated, and the complex morphogenetic movements which occur during the formation of the head capsule of the insect are described. The initial contact between the eye anlagen is by means of cell processes spanning the gap between the two discs. Subsequently the two epithelia become firmly apposed, and then the integrity of the epithelium in the region of fusion breaks down, cells appearing to move to new positions in order to form an epithelium which unites the two discs. The epithelium eventually secretes a pattern of cuticular structures which is continuous between the derivatives of the two discs. Bristles on either side of the line of fusion are perfectly aligned, and structures such as the median ocellus, which are formed jointly by the cells of the two discs, differentiate normally. This is also found when left and right eye-antennal discs of different genotypes are placed side-by-side, indicating that processes of pattern regulation can occur in culture.
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  • 28
    ISSN: 1432-2048
    Keywords: Immunocytochemistry ; Lectin (localization) ; Phaseolus (lectin) ; Phytohemagglutinin ; Seed (lectin)
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    Topics: Biology
    Notes: Abstract We have examined the properties and subcellular localization of phytohemagglutinin (PHA), the major lectin of the common bean (Phaseolus vulgaris.), in the axis cells of nearly mature and imbibed mature seeds. On a protein basis the axis contained about 15% as much PHA as the cotyledons. Localization of PHA was done with an indirect immunolabeling method (rabbit antibodies against PHA, followed by colloidal gold particles coated with goat antibodies against rabbit immunoglobulins) on ultra-thin cryosections which were embedded in plastic on the grids after the immunolabeling procedure. The embedding greatly improved the visualization of the subcellular structures. The small (4 nm) collodial gold particles, localized with the electron microscope, were found exclusively over small vacuoles or protein bodies in all the cell types examined (cortical parenchyma cells, vascular-bundle cells, epidermal cells). The matrix of these vacuoles-protein bodies appears considerably less dense than that of the protein bodies in the cotyledons, but the results confirm that in all parts of the embryo PHA is localized in similar structures.
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  • 29
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    European journal of clinical pharmacology 21 (1982), S. 287-291 
    ISSN: 1432-1041
    Keywords: tolmesoxide ; hypertension ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Tolmesoxide is a new, direct-acting vasodilator drug for use in the management of both hypertension and cardiac failure. In 6 essential hypertensives inadequately controlled by combined β-blocker and diuretic therapy (average supine blood pressure 178/103 mm Hg) the addition of tolmesoxide (300–900 mg daily) was associated with a significant improvement in blood pressure control (average supine blood pressure 161/89 mmHg). The effect of food on the pharmacokinetics and pharmacodynamics of tolmesoxide have also been studied because, particularly at higher doses, the drug has been associated with upper gastrointestinal upset and it has been empirically recommended that it be taken with food. The blood pressure and heart rate responses were not significantly different when tolmesoxide was taken fasting or with food. Food resulted in a significant reduction in the peak plasma tolmesoxide concentration (2.14 µg/ml compared to 2.97 µg/ml) and a significant increase in the time to reach peak plasma concentration (1.67 h compared to 0.63 h). Although there was no impairment of its hypotensive effect, food significantly altered the pharmacokinetics of tolmesoxide and may therefore be useful in reducing the gastrointestinal disturbance associated with its use. In the treatment of inadequately controlled hypertension, tolmesoxide has a limited role as an alternative vasodilator.
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    European journal of clinical pharmacology 21 (1982), S. 363-367 
    ISSN: 1432-1041
    Keywords: labetalol ; clonidine ; hypertension ; dose titration ; bendrofluazide ; side effects
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of labetalol (L) was compared with that of clonidine (C) in a randomized cross-over study in 17 hypertensive outpatients on bendrofluazide (B). After treatment for two weeks with B (5 mg qd), either L (100 mg tid) or C (0.1 mg tid) was given and their doses were titrated at 2-weekly visits until normotension was achieved, or intolerable side-effects occurred. The treatment with B and L or C was then continued in a cross-over fashion for two 6-week periods, with 3 week diuretic washouts and subsequent dose-titration periods between the treatment periods. At the end of B, the supine blood pressure (BP) was 156/101, and at the end of B + L and B + C it was 136/91 (p〈0.001) and 137/91 (p〈0.001), respectively, pooling the data from both periods. At the end of B, the standing BP was 155/115, and at the end of B + L and B + C 134/100 (p〈0.001) and 139/106 (p〈0.001), respectively. The mean daily doses required were L 476mg and C 0.335 mg. On a weight basis, labetalol had about 1/1400 of the potency of clonidine. 12 patients complained of tiredness and dry mouth on clonidine and 2 patients of unsteadiness on labetalol. Labetalol caused a psoriasiform rash on the hands in one patient and limb weakness in one patient.
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    European journal of clinical pharmacology 22 (1982), S. 7-14 
    ISSN: 1432-1041
    Keywords: prazosin ; baroreflexes ; hypertension ; reflex tachycardia ; alpha adrenergic blockade ; dopamine-beta-hydroxylase
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prazosin is a post synaptic alpha adrenergic blocker effective in hypertension, whose hypotensive effect is unaccompanied by reflex tachycardia or hyperreninemia, nor by other evidence of increased sympathetic activity. We studied the baroreceptor reflex arc as a potential mediator of these effects. Twenty-two essential hypertensive men were treated with prazosin alone versus placebo, and experienced a blood pressure fall (from 114.8±3.6 down to 101.1±2.5 mm Hg,p〈0.005) unaccompanied by any change in heart rate, plasma renin activity, or several other indices of sympathetic nervous system activity (plasma dopamine-β-hydroxylase activity; urinary excretion of free catecholamines and vanillyl mandelic acid; allp〉0.1). Concomitant with the blood pressure fall, there was a significant depression of baroreflex arc sensitivity, from 11.4±2.0 ms/mmHg down to 6.6±1.9 ms/mmHg (p〈0.05), without an associated change in cardiac vagal inhibition (291.2±46.2 versus 300.3±19.2 ms,p〉0.1). Baroreflex arc sensitivity depression may in part explain the lack of reflex sympathetic outflow noted during prazosin treatment of hypertension.
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    European journal of clinical pharmacology 22 (1982), S. 197-201 
    ISSN: 1432-1041
    Keywords: hypertension ; oxprenolol ; indomethacin ; drug interaction ; hypotensive effect
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A double-blind, cross-over study in 16 patients with essential hypertension was carried out, to evaluate any possible interference by indomethacin, a known prostaglandin-synthetase inhibitor, with the antihypertensive effect of oxprenolol, a non-selective beta-adrenoceptor blocking agent. Both indomethacin and oxprenolol, as well as the two drugs combined, inhibited plasma renin activity; no change was found in urinary sodium excretion or body weight. Oxprenolol alone caused a highly significant decrease in the systolic (−10.4 mmHg,p〈0.001), diastolic (−7.4 mmHg,p〈0.001) and mean (−7.7 mmHg,p〈0.01) blood pressures, whereas indomethacin did not influence blood pressure. When the two drugs were given in combination, blood pressure decreased (systolic: −5.9 mmHg; diastolic: −4.0 mmHg; mean: −4.6 mmHg), but the changes induced in blood pressure were reduced by about 50% when compared with those in the oxprenolol alone period. The data show that indomethacin seems to interfere with the antihypertensive effect of oxprenolol, by an action which may be due to the inhibition of prostaglandin synthesis.
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    European journal of clinical pharmacology 22 (1982), S. 495-499 
    ISSN: 1432-1041
    Keywords: hypertension ; cyclothiazide ; hydrochlorthiazide ; thiazide diuretics ; potassium-sparing diuretics ; saluretic effect ; hypokalaemia ; hyperuricaemia ; amiloride
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive, saluretic and hypokalaemic effects of a small dose of cyclothiazide (2.5 mg daily) were compared with those of a conventional dose of an hydrochlorthiazide-amiloride hydrochloride combination (50+5 mg daily). Both preparations were given to 13 patients with mild (WHO I) hypertension in a cross-over manner for six weeks, with an intervening wash-out phase of three weeks. The antihypertensive efficacy of cyclothiazide was well comparable to that of the hydrochlorthiazide-amiloride combination, although cyclothiazide tended to inhibit renal sodium reabsorption less than the combination. Cyclothiazide tended to cause hypokalaemia, apparently due to increased potassium loss, but with the present dosage none of the 13 patients developed marked hypokalaemia (serum potassium less than 3.3 mmol/l). Both drugs led to a comparable increase in serum urate concentration. Neither of the preparations affected creatinine or free-water clearance. The results suggest that even in relatively small doses thiazides effectively decrease blood pressure, and combining thiazides with potassium-sparing diuretics is advantageous only in patients with marked hypokalaemia and its associated risks.
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    European journal of clinical pharmacology 26 (1984), S. 309-313 
    ISSN: 1432-1041
    Keywords: clonidine ; hypertension ; therapeutic window ; steady state concentration ; pharmacokinetics ; cardiovascular effects
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Clonidine was given orally as monotherapy in increasing daily doses from 3.1 to 25.7 µg/kg to patients with essential hypertension (n=6). When a steady state concentration in plasma was reached at each dose level, the blood pressure (BP) and heart rate were measured during a dosage interval. Effect time — plasma concentration data were submitted to nonlinear regression analysis, which showed that the observed BP effects could be dissociated into depressor and pressor components. A window for the antihypertensive effect was established. At a plasma clonidine concentration of 0.65±0.07 ng/ml 50% of the maximal depressor effect was found, and it was only separated by a factor of 2 from the half maximal pure pressor concentration in plasma. No relationship between the change in heart rate and the plasma clonidine was observed. The findings strengthen the importance of close monitoring of clonidine therapy.
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  • 35
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    European journal of clinical pharmacology 26 (1984), S. 331-334 
    ISSN: 1432-1041
    Keywords: metoprolol ; oxprenolol ; hypertension ; beta-blockers ; HDL-cholesterol ; intrinsic sympathomimetic activity ; cardioselectivity
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The aim of the present study was to evaluate whether a reduction in HDL-cholesterol is peculiar to non cardioselective beta blockers or whether it is also produced by cardioselective beta1-blockers. 16 patients with primary arterial hypertension on a balanced isocaloric diet were given oxprenolol 120 to 240 mg/day or metoprolol 100 to 200 mg/day in a random cross-over study. No significant change was observed after either treatment in fasting blood glucose, serum total cholesterol and triglycerides. HDL-cholesterol concentration was significantly decreased on metoprolol, from 41 to 36 mg/dl (p〈0.05), while oxprenolol did not affect it at all. The difference might depend on intrinsic sympathomimetic activity which is possessed by oxprenolol and which metoprolol lacks.
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  • 36
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    European journal of clinical pharmacology 26 (1984), S. 549-553 
    ISSN: 1432-1041
    Keywords: pafenolol ; hypertension ; antihypertensive therapy ; beta1-blocking agent ; exercise tests ; plasma levels
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pafenolol, a new selective adrenergic beta1-blocking agent, has been tested for the first time in 6 hypertensive patients. After single oral doses of pafenolol 25 to 100 mg, there was a marked reduction in heart rate and systolic blood pressure during exercise tests. These effects were dose dependent. A significant positive correlation was found between the reduction in heart rate during exercise and the plasma level of pafenolol 5 hours after drug intake (correlation coefficient r=0.94). Side effects were mild and seemed to be dose dependent. It is concluded that this new beta1-blocking agent was effective in reducing blood pressure and was well tolerated.
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  • 37
    ISSN: 1432-1041
    Keywords: etozolin ; ozolinone ; furosemide ; hypertension ; renin ; catecholamines ; chronic renal failure ; steady state kinetics ; plasma levels
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect on urinary electrolyte excretion, renin release and plasma norepinephrine of single oral doses of 400 mg etozolin (E) and of 40 mg furosemide (F) were studied in hypertensive patients with normal (n=6) and impaired kidney function (n=6). E caused a marked saluresis up to 24 hours, showing its long duration of action. F, however, displayed a brief, brisk peak diuresis, followed by a rebound from the 4th to the 24th hours. The brisk peak diuresis induced by F was associated with pronounced release of renin, almost twice that induced by E. In chronic renal failure the renin release in relation to the magnitude of the diuresis was increased, i.e. the sensitivity of these patients to changes in water homeostasis was increased. E and F stimulated the sympathetic system to roughly the same extent. Patients with essential hypertension had higher plasma levels of norepinephrine than hypertensive patients with chronic renal failure. In addition, hypertensive patients with normal renal function (n=4) and varying degrees of renal impairment (n=11) were also given 400 mg daily for 2 weeks. Effects on blood pressure and electrolyte homeostasis were monitored, as well as the plasma kinetics of metabolite I, ozolinone. At the end of the 2 week treatment E had significantly lowered systolic (−12 mm Hg) and diastolic (−9 mm Hg) blood pressure, and had produced a significant loss of body weight, without altering plasma electrolytes or blood chemistry. There was no accumulation of the effective metabolite ozolinone under conditions of severe impairment of kidney function. It is concluded that E can effectively control high blood pressure in patients with normal and impaired kidney function. Its effective metabolite ozolinone did not accumulate in chronic renal failure.
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  • 38
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    European journal of clinical pharmacology 27 (1984), S. 397-405 
    ISSN: 1432-1041
    Keywords: indapamide ; hypertension ; cardiovascular reflexes ; diuretic effect ; blood pressure variability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine elderly and 11 young hypertensives underwent continuous ambulatory monitoring of blood pressure (BP), assessment of cardiovascular reflexes and M-mode echocardiography as hospital in-patients prior to treatment with once-daily indapamide (2.5 mg). They were followed as out-patients for 4 months during which time casual BP was measured at monthly intervals. The patients were then readmitted to hospital and studied using the same protocol under similar standardised conditions. The results showed that indapamide reduced casual and ambulatory BP in both young and elderly although the most marked effect was seen on systolic BP. Assessment of cardiovascular reflexes indicates that at least part of the hypotensive action of indapamide is due to a diuretic effect. Treatment with indapamide has comparable results on both young and elderly.
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  • 39
    ISSN: 1432-1041
    Keywords: beta-blocker ; hypertension ; clonidine ; plasma catecholamines ; metoprolol ; propranolol ; blood pressure responses ; isometric work ; dynamic work
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of metropolol (beta1-selective), propranolol (nonselective) and clonidine (central alpha-stimulant) on plasma norepinephrine, blood pressure and heart rate were assessed at rest, during isometric work and dynamic exercise in 15 patients with moderate hypertension. Metroprolol resulted in a lower diastolic blood pressure during isometric and dynamic exercise than propranolol, which was paralleled by a lower plasma norepinephrine level during dynamic work; both beta-adrenergic blocking compounds resulted in a lower heart rate in all test situations than that obtained with clonidine; clonidine produced similar control of diastolic blood pressure to that obtained with the beta-adrenergic blocking agents, but did not clearly attenuate the systolic blood pressure response to dynamic exercise. Plasma norepinephrine concentrations tended to be lowest following clonidine, especially during dynamic work. The findings support the hypothesis that the central action of clonidine inhibits peripheral release of norepinephrine, but is insufficient to attenuate cardiac stimulation by physical exercise. The fact that propranolol caused higher plasma norepinephrine concentrations than metoprolol during exercise may explain the difference in the blood pressure responses during exercise.
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    European journal of clinical pharmacology 21 (1982), S. 445-449 
    ISSN: 1432-1041
    Keywords: pindolol ; hypertension ; retard formulation ; plasma levels ; side effects
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 36 out of 52 patients with essential hypertension, whose blood pressure was not normalized with pindolol 15 mg per day, were treated with 30 mg per day for four to six weeks. Pindolol was administered in random order, either as 15 mg twice daily or as one 30 mg retard tablet once daily. Blood pressure was lowered from mean pretreatment levels of 174/111 mmHg to 149/98 mmHg by 15 mg b.d., and to 145/97 mmHg by 30 mg retard. In five patients diurnal variations in blood pressure and plasma pindolol levels were determined. At all times during the day blood pressure was at least as well controlled by 30 mg retard as by 15 mg b.d. Plasma concentration maxima were similar with both forms, but a higher concentration was maintained for a longer time after the retard tablet. Pindolol 30 mg was well tolerated and the incidence of side effects was lower than during treatment with 15 mg b.d. Thus, patients requiring high doses of pindolol for control of hypertension can safely and conveniently be treated with a single tablet of 30 mg pindolol retard.
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    European journal of clinical pharmacology 21 (1982), S. 473-477 
    ISSN: 1432-1041
    Keywords: tolmesoxide ; vasodilators ; heart failure ; haemodynamics ; hypertension ; sulphoxide
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic effect of Tolmesoxide, a new sulphoxide chemically dissimilar from other vasodilators, was investigated in eight patients with chronic heart failure subsequent to ischaemic heart disease and/or hypertension. Tolmesoxide significantly increased the cardiac output and reduced the indices of systemic vascular resistance, the mean pulmonary arterial pressure and left ventricular filling pressure in most patients studied. These changes were observed both as acute and chronic effects. No significant effect on the mean arterial pressure, heart rate or myocardial oxygen supply/demand was observed. Tolmesoxide appeared to be therapeutically potent by both intravenous and oral routes.
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    European journal of clinical pharmacology 22 (1982), S. 285-288 
    ISSN: 1432-1041
    Keywords: hypertension ; plasma adrenaline ; plasma noradrenaline ; isoprenaline response ; noradrenaline response ; salivation ; parasympathetic nervous system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Parameters of the autonomic nervous system were studied in normotensive subjects (NT; standing blood pressure (BP)≤125/85 mmHg) and in subjects with borderline hypertension (BHT; 140/90≤standing BP〈60/100 mmHg). No differences in plasma noradrenaline and adrenaline levels were found between NT and BHT subjects, neither at rest nor during exercise at 75% of maximum work capacity. The dose of noradrenaline required to increase systolic BP by 10 mmHg was significantly higher in NT than in BHT subjects (5.13±0.42 vs 3.50±0.57 µg · min−1). No difference between NT and BHT subjects was found in the dose of isoprenaline required to increase heart rate by 20 beats · min−1 (1.21±0.12 vs 1.09±0.11 µg · min−1). Resting salivary flow was significantly lower in BHT than in NT subjects (0.39±0.06 vs 0.98±0.06 g · min−1), suggesting decreased parasympathetic activity in the former group. The enhanced pressor effect of noradrenaline, together with the decreased parasympathetic activity, could explain the elevated blood pressure and heart rate in subjects with borderline hypertension.
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  • 43
    ISSN: 1432-1041
    Keywords: bopindolol ; hypertension ; beta-blocker ; blood pressure ; plasma renin ; plasma catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Bopindolol (LT 31-200), a new, long-acting, non-selective beta-blocker, was given as monotherapy to 13 patients, 12 with essential hypertension and 1 with renovascular hypertension. After a placebo period of 4–6 weeks, bopindolol was given once daily, starting with 1 mg and subsequently increasing at two-weekly intervals to 2 and 4 mg once daily until a diastolic blood pressure⩽90 mmHg was achieved. The effective dose was continued for 12 weeks. In 10 patients plasma levels of renin, noradrenaline, adrenaline and cholesterol were measured during placebo and after 3 months of therapy. Blood pressure and heart rate were lowered significantly during bopindolol treatment. The mean effective dose was 2.2 mg per day. In 10/13 patients a diastolic blood pressure⩽90 mmHg was achieved. Side effects were minimal. Changes in plasma noradrenaline and adrenaline were small and not significant, but renin and cholesterol were significantly reduced. Thus, LT 31-200 is an effective and well tolerated beta-blocker when given in a once daily dosage.
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  • 44
    ISSN: 1432-1041
    Keywords: hypertension ; nifedipine ; beta-adrenoceptor blockade ; long-term treatment ; adverse effects ; propranolol ; timolol ; metoprolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of nifedipine during long-term therapy was investigated in 5 patients receiving nifedipine as the sole drug and in 10 patients who had nifedipine in combination with a beta-adrenoceptor blocking drug. Nifedipine monotherapy was problematic because of side-effects and development of resistance to therapy after a few months. In patients who received the combined therapy significant and stable blood pressure reductions were maintained during the whole observation period (12–33 months). However, the occurrence of peripheral oedema in 4 of the patients necessitated the addition of a thiazide diuretic. It is concluded that nifedipine is not a first choice drug for the long-term treatment of arterial hypertension. When given in addition to a beta-blocker it is well tolerated and powerful but fluid retention may occur and if not counteracted by a diuretic it will limit the antihypertensive potential of the drug.
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  • 45
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    European journal of clinical pharmacology 23 (1982), S. 197-201 
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; low dose ; plasma concentration ; acute and long-term treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute and long-term hypotensive effects of low doses of nifedipine, and the correlation between the fall in the blood pressure (BP) and the plasma nifedipine concentration, were investigated in patients with essential hypertension. The oral administration of nifedipine 5 mg rapidly decreased BP from 163±22/101±10 to 127±12/82±9 mmHg (mean±SD; p〈0.001), and increased heart rate from 72±8 to 76±6 beats/min (p〈0.05), plasma renin activity rose from 1.2±0.6 to 1.4±0.8 ng/ml/h (p〈0.05), and plasma nifedipine concentration was 75.6±22.0 ng/ml 30 min after administration (n=7). The nifedipine concentration was significantly correlated both with the fall in BP (r=0.410, p〈0.02, n=31) and the rise in the heart rate (r=0.412, p〈0.02, n=31). Treatment with nifedipine 5 mg t.d.s. alone or in combination either with propranolol 10 mg t.d.s., or thiazide 1 tablet daily, or propranolol and thiazide, controlled BP in 36 patients during the 22 week study period. During the long-term nifedipine therapy, the plasma nifedipine level was significantly correlated with the fall in systolic (r=0.577, p〈0.01, n=20) and diastolic (r=0.595, p〈0.01, n=20) BP. It was concluded that the plasma nifedipine concentration could be correlated with the fall in BP, and that low doses of nifedipine, either as monotherapy or in combination, were effective in the acute and long-term treatment of patients with essential hypertension.
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  • 46
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    European journal of clinical pharmacology 23 (1982), S. 215-220 
    ISSN: 1432-1041
    Keywords: hypertension ; muzolimine ; mild renal functional impairment ; diuretic treatment ; body sodium ; catecholamines ; cardiovascular pressor responsiveness
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eighteen patients with mild impairment of renal function (glomerular filtration rate 65±5 ml/min: m±SEM) and hypertension (168/105±6/3 mmHg) were shown on average to have abnormally increased cardiovascular pressor responsiveness to infused norepinephrine (NE; p〈0.05), whereas plasma and urinary NE, exchangeable body sodium and blood-volume did not differ significantly from normal. A slightly increased pressor responsiveness to angiotensin II was associated with a tendency to low plasma renin activity (PRA). Compared to placebo conditions, treatment with the loop-diuretic muzolimine in a mean dose of 35±2 mg/day for six weeks decreased blood-pressure and exchangeable sodium (p〈0.05), and NE pressor responsiveness was restored to normal values, whilst plasma and urinary NE were not significantly changed. This was consistent with improvement of the initially abnormal relationship between NE levels and NE responsiveness factors. In contrast, the pressor dose of angiotensin II and PRA were increased to an approximatively similar extent during muzolimine treatment. These observations suggest that removal of body sodium and a decrease in NE reactivity without an equivalent increase in sympathetic nervous activity may be important complementary factors in the antihypertensive mechanisms of diuretic treatment in patients with mild renal functional impairment.
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  • 47
    ISSN: 1432-1041
    Keywords: prizidilol ; vasodilator ; hypertension ; beta blocker ; plasma renin ; aldosterone ; catecholamines ; acetylator type
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prizidilol is a new antihypertensive agent reported to possess combined precapillary vasodilator and betareceptor-blocking properties. To clarify the profile of the acute effects of prizidilol in man, a variable dose study was performed in 8 patients with benign essential hypertension. Blood pressure, heart rate, plasma renin activity, aldosterone, plasma and urinary catecholamines and electrolytes were determined at short intervals before and up to 23 h after oral administration of placebo and prizidilol 150, 300 and 600 mg. The 4 studies were performed at weekly intervals according to a Latin square design. Prizidilol produced dose-dependent decreases in supine and upright blood pressure, with an initial change after about 2 h and maximal effects from 4 to 8 h after drug ingestion. Following a high dose of prizidilol, supine mean blood pressure (average 128 mmHg prior to treatment) was normalised (〈107 mmHg) from 3 to 7 h and was still below predose levels 23 h after ingestion. The only reported side effects were postural dizziness in 2 cases (corresponding to a fall in systolic upright blood pressure to 〈95 mmHg) and headache in one case. A biphasic variation in heart rate and plasma renin activity, with an early drop and a subsequent tendency to a slight rise, was observed after an intermediate or high dose of prizidilol. Plasma norepinephrine levels were increased by a high dose of prizidilol, while plasma epinephrine, aldosterone and plasma and urinary electrolytes were not consistently changed. Prizidilol in a single oral dose appeared to be a potent antihypertensive agent. The profile of heart rate and plasma renin point to early dominance of beta-blockade followed by appearance of the concomitant vasodilator properties of prizidilol.
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  • 48
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    European journal of clinical pharmacology 26 (1984), S. 315-323 
    ISSN: 1432-1041
    Keywords: captopril ; hypertension ; glomerular filtration ; para-aminohippuric acid ; renal function ; severe drug reaction ; nephrotic syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of captopril up to 450 mg/day on blood pressure and renal function were investigated during sustained treatment of 10 patients whose severe hypertension had not responded to previous therapy. All the patients were kept on diuretics and most of them on β-blockers, too. A control determination of glomerular filtration rate (GFR) and para-aminohippuric acid clearance (CPAH) was performed during the prior treatment. The effect of the addition (or substitution) of captopril were assessed after an average of 25 days (short-term) and 26 weeks (long-term). Short-term treatment produced a 15.5% decrease in mean blood pressure and interindividually variable effects on renal function. On average GFR was somewhat lower and CPAH slightly higher than the control values (not significant). This pattern is quite similar to the effects of most other antihypertensive drugs. On long-term therapy GFR rose by a mean of 9% (NS) and CPAH by 17% (p〈0.02). However, in a patient who developed a captopril-induced nephrotic syndrome, GFR dropped to 56% and CPAH to 50% of the control values. In another patient a transient rise in serum creatinine accompanied a severe drug reaction.
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  • 49
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    European journal of clinical pharmacology 21 (1982), S. 263-267 
    ISSN: 1432-1041
    Keywords: hypertension ; spironolactone ; hypotensive action ; peripheral circulation ; plethysmography ; handgrip test ; cold pressure test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Since there is only scanty, indirect information about the mechanism of the hypotensive effect of spironolactone, 9 patients with essential hypertension were studied according to a randomised double-blind, cross-over protocol. Spironolactone 100mg b.i.d. and placebo were each given for one month and the following parameters were studied: blood pressure, heart rate, response to cold pressure and hand-grip tests, as well as blood flow in the calf and finger vessels. Flow in the calf and fingers representing muscle and skin arteries, respectively, was measured semicontinuously with an ECG-triggered venous occlusion plethysmograph. After spironolactone there was a significant decrease in the systolic and diastolic blood pressures in the supine, sitting and standing positions; the sitting systolic and diastolic blood pressure decreased by (mean ± SE) 27±4mm Hg (p〈0.001) and 11±4mm Hg (p〈0.02), respectively. No orthostatic response was observed. Heart rate remained unchanged. Blood flow through muscle and skin vessels increased in 6 out of 9 patients, and in these patients calculated vascular resistance in these areas decreased. Spironolactone did not significantly change the response of systemic blood pressure to the handgrip and cold pressure tests. The present data confirm the hypotensive properties of spironolactone and show that this effect is associated with dilatation of muscle and skin arteries in many but not in all the patients. The data do not support the hypothesis that spironolactone decreases the responsiveness of systemic blood pressure to orthosympathetic stimulation.
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  • 50
    ISSN: 1432-1041
    Keywords: hypertension ; indapamide ; pindolol ; plasma renin activity ; plasma aldosterone concentration
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen patients with essential hypertension completed a double blind factorial trial comparing the effects of indapamide (2.5 mg daily) and pindolol (10 mg daily) on blood pressure, heart rate, plasma renin activity and plasma aldosterone concentration. There were four randomised test phases of eight weeks each during which patients received indapamide alone, pindolol alone, indapamide plus pindolol and no active treatment (placebo). Blood pressure and heart rate were measured every two weeks. Supine mean arterial pressure fell from 117 mm Hg in the placebo phase to 111 mm Hg in the indapamide phase, 106 mm Hg in the pindolol phase and 103 mm Hg in the combined indapamide plus pindolol phase. Factorial analysis confirmed that the hypotensive effects of the two drugs were additive, without evidence of potentiation or antagonism. Indapamide caused significant reductions in plasma potassium and chloride, and increases in plasma bicarbonate and urate concentrations; it also caused increases in plasma renin activity and aldosterone concentration. These changes are similar to those observed with thiazide diuretics.
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  • 51
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    European journal of clinical pharmacology 22 (1982), S. 487-489 
    ISSN: 1432-1041
    Keywords: nadolol ; hypertension ; effective dose range ; compliance
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An open, observer-blind, therapeutic titration trial was carried out in 28 patients with mild or moderate essential hypertension to determine the effective dose range of nadolol given once a day. 11 patients became normotensive (supine diastolic blood pressure 90 mm Hg or below) with 80 mg, 4 with 120 mg and 1 with 160 mg. The largest step in the reduction of blood pressure was achieved with the first dose step of 80 mg, and only a small, non-significant further decrease was obtained with higher dose levels. Thus, nadolol, unlike propranolol, has a narrow effective dose range, and this should permit a brief dose adjustment period, which would be important in improving patient compliance.
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  • 52
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    European journal of clinical pharmacology 23 (1982), S. 93-97 
    ISSN: 1432-1041
    Keywords: tolmesoxide ; vasodilator ; hypertension ; pharmacokinetics ; haemodynamics ; plasma renin activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic response and pharmacokinetics of single dose oral tolmesoxide were studied at various dose levels in 4 patients with severe hypertension. There was a reproducible fall in mean arterial pressure from baseline of 24.2% and a rise in heart rate of 37.6% following administration of tolmesoxide. The onset of antihypertensive action occurred within 1 h, with a peak effect at 3 h after dosing. The mean duration of action was up to 12.0 h. Tolmesoxide had a mean half-life of 3.0 h. It was rapidly absorbed with a mean peak plasma level occurring at 1.0 h. Plasma levels correlated well with the doses administered. Side-effects included mild nausea, facial flushing and postural symptoms.
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  • 53
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    European journal of clinical pharmacology 21 (1982), S. 457-460 
    ISSN: 1432-1041
    Keywords: hypertension ; propranolol ; hydralazine ; labetalol
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a randomised cross-over trial the combination labetalol/hydrochlorothiazide was compared with the combination of propranolol/hydralazine/hydrochlorothiazide in 34 uncomplicated hypertensive patients, who were not satisfactorily controlled with hydrochlorothiazide 50 mg alone. The elevated diastolic pressure (D.P.) in 27 patients responded satisfactorily to the labetalol schedule and in 28 patients to the propranolol/hydralazine schedule. No difference was found in the rate of decrease of D.P., nor in the disappearance of hypertension — related complaints. Although the duration of the washout between treatments was at least one month, treatment was significantly more efficacious during the second period. Labetalol pre-treatment especially seemed to enhance the effect of subsequent propranolol/hydralazine administration. Side effects due to therapy were rare and were not related to any particular treatment. The median daily dose of labetalol in responders was 600 mg and that of propranolol/hydralazine 120/60 mg (in both therapies hydrochlorothiazide 50 mg was given in addition). Patients showed a slight preference for the labetaol medication. It is concluded that labetalol/hydrochlorothiazide and propranolol/hydralazine/hydrochlorothiazide are equally satisfactory in the treatment of uncomplicated hypertension.
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  • 54
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    European journal of clinical pharmacology 22 (1982), S. 203-206 
    ISSN: 1432-1041
    Keywords: hypertension ; ticrynafen ; hydrochlorothiazide ; renal impairment ; uricosuria ; diuretic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The efficacy of ticrynafen in the treatment of hypertension in patients with moderate renal impairment was compared with that of hydrochlorothiazide in a randomised, double-blind crossover trial in eleven subjects with renal insufficiency. Significant reductions in blood pressure occurred with both treatments, with the maximum responses occurring at different time intervals and to different degrees in individual patients. Thus, although ticrynafen caused a significant reduction in blood pressure in this group of hypertensive patients with renal insufficiency, it was not consistently different from that which could be achieved with hydrochlorothiazide. Ticrynafen also significantly reduced the serum uric acid concentration, compared with a significant rise with hydrochlorothiazide. No major biochemical abnormalities or side-effects were encountered in any subject. Thus, in these patients with renal insufficiency, ticrynafen still demonstrated a uricosuric effect as well as a useful anti-hypertensive action.
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  • 55
    ISSN: 1432-1041
    Keywords: labetalol ; chlorthalidone ; hypertension ; fixed combination ; antihypertensive therapy ; side effects ; multicentre study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a multicentre, double-blind, crossover, placebo-controlled study, the antihypertensive effect of labetalol 100 mg and chlorthalidone 10 mg, given alone or in combination, has been assessed in 32 hypertensive patients. The combination had a greater effect in reducing blood pressure than did its separate components. This was particularly evident after exercise. Heart rate increased during chlorthalidone therapy, decreased during labetalol therapy, and a summation effect was observed during treatment with the combination. In most cases additivity was observed, as no interaction between the single components was observed, except for heart rate after exercise, and for diastolic blood pressure in the upright position. No interaction was observed either in the biochemical indices or in the clinical side-effects.
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  • 56
    ISSN: 1432-1041
    Keywords: beta-blocking drugs ; insulin sensitivity ; pancreatic beta-cell function ; hypertension ; propranolol ; atenolol ; insulin secretion ; plasma GIP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of two beta-blocking drugs on endogenous insulin secretion and insulin sensitivity were investigated in a double blind cross-over study in 13 hypertensive patients. The patients were randomly allocated to each of three 2-week treatment periods with propranolol 80 mg b.i.d., atenolol 50 mg b.i.d. and placebo b.i.d. Endogenous insulin secretion was assessed by measuring serum insulin and C-peptide before and 6 min after iv administration of glucagon; insulin sensitivity was determined by measuring insulin binding to erythrocytes, and as the glucose disappearance rate (KITT) after i.v. insulin. Fasting concentrations of serum free fatty acids (S-FFA) and plasma gastric inhibitory polypeptide (P-GIP) were also recorded during the three study periods. Both propranolol and atenolol reduced blood pressure, heart rate and S-FFA concentrations compared to placebo, and all patients showed measurable plasma concentrations of propranolol and atenolol. The results can be considered representative, therefore, of clinical beta-blockade. The two drugs did not significantly influence the fasting blood glucose level. There was an increase in fasting and glucagon-stimulated serum C-peptide concentration during propranolol therapy compared with placebo (p=0.037 and p=0.030, respectively), although this was not reflected by a significant change in serum insulin. Propranolol and atenolol did not significantly influence insulin binding to erythrocytes, but they clearly reduced the glucose disappearance rate KITT was compared to placebo (p=0.0036 and p=0.0003, respectively). The findings support the view that beta-blocking drugs can influence glucose metabolism by mechanisms other than inhibition of endogenous insulin secretion.
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  • 57
    ISSN: 1432-1041
    Keywords: acetylator phenotype ; hydralazine response ; hypertension ; blood pressure control ; lupus syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The role of acetylator phenotype in determining the response to hydralazine when it was added to diuretic and β-blocker at doses not exceeding 200 mg daily was examined in 57 hypertensive patients. 81% of rapid acetylators needed 200 mg hydralazine daily compared to 38% of slow acetylators (p〈0.01). Despite higher doses of hydralazine the blood pressure was controlled in only 27% of rapid acetylators compared to 65% of slow acetylators (p〈0.02). The relation of acetylator phenotype to blood pressure response was statistically independent of initial blood pressure, age, sex, body weight and serum creatinine (p〈0.005). Current recommendations on hydralazine dosage are unsatisfactory for the 40% of hypertensive patients who are rapid acetylators. We suggest measurement of the acetylator phenotype in patients who respond incompletely to 200 mg hydralazine daily. About 70% of these patients will be rapid acetylators in whom the dose of hydralazine can be increased safely.
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  • 58
    ISSN: 1432-1041
    Keywords: Tobanum® ; beta-blocker ; chloranolol ; hypertension ; angina pectoris ; arrhythmia ; detection methods
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The incidence of side-effects on administration of chloranolol (Tobanum®), a beta-adrenergic receptor blocking drug, to 2066 patients with hypertension, angina pectoris or arrhythmias was measured by three different methods. In 600 patients in an efficacy trial (Group 1) both spontaneously reported complaints and objective signs were tabulated. A side effect — directed method, utilising a questionnaire containing a list of possible side-effects was also used, with the questionnaire being completed by the physician. 35 questions referred to anticipated and other side-effects. The trial was performed in two groups: in 537 patients a placebo was also given (Group 2), and in another set of 929 patients (Group 3) the questionnaire inquiry was performed uncontrolled, without placebo. All three groups were comparable in their distribution of sexes, ages and diagnoses, the mean daily dose of chloranolol its use alone or in combination, and in a similar duration of treatment. 55% of all patients received chloranolol therapy for a period of more than 3 months. The ratio of in- and outpatients was 1:5. The side-effect incidence was independent of the age and sex of the patients and of the dose of chloranolol. The incidence was also unaffected whether chloranolol was used alone or in combination. The number of side-effects differed markedly between the three groups, their ratio was 1:10:24 in Groups 1, 2 and 3. Two-thirds of the side-effects subsided spontaneously within 1 month of their onset. The duration of the side-effects varied according to their character: cardiorespiratory side-effects were of the shortest duration and those affecting the central nervous system were the most enduring. The appreciable differences in incidence could be attributed to the methods of collection of the data. It has been stated that placebo controlled trials using a detailed questionnaire are the most suitable for estimating the incidence of side-effects; recording side-effects spontaneously reported by patients are insufficiently sensitive, and uncontrolled trials using a questionnaire have been shown to be too sensitive. The revealed incidence of side effects leading to interruption of treatment is less affected by the method chosen. In 100 patients (4.8%) therapy had to be suspended because of the side-effects of chloranolol (Group 1: 1%, Group 2: 6.20%, Group 3: 6.6%). Comparison of the incidence of cessation of therapy due to side-effects did not show an appreciable difference between the various beta-adrenergic receptor blocking agents, including chloranolol.
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  • 59
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    European journal of clinical pharmacology 26 (1984), S. 1-6 
    ISSN: 1432-1041
    Keywords: hypertension ; beta-blockers ; propranolol ; metoprolol ; labetalol ; exercise ; heart rate ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double blind, within patient investigation of twenty-four patients (nineteen males and five females) with a mean age of 46.3 years (SD 10.9 years) with mild to moderate essential hypertension a comparison between equipotent beta-blocking doses of propranolol, metoprolol and labetalol was carried out. Blood pressure and pulse rate were measured in lying, sitting and standing positions and before, during and after isometric and dynamic exercise. Peak expiratory flow was recorded before and during dynamic exercise. All the active treatments were better than placebo in reducing blood pressure and heart rate. Comparing the effects of treatment, labetalol lowered sitting diastolic pressure significantly more than propranolol and standing diastolic pressure than both propranolol and metoprolol. Metoprolol and propranolol were more effective in reducing heart rate. Propranolol significantly reduced peak flow rate compared to labetalol. During the exercise, both isometric and dynamic, the heart rate and the blood pressure, both systolic and diastolic, of the treated patients were lower than those on placebo. There was little difference between the drugs in the influence on blood pressure, but metoprolol and propranolol were significantly more effective than labetalol in lowering the heart rate.
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  • 60
    ISSN: 1432-1041
    Keywords: alpha-methyldopa ; propranolol ; hypertension ; side effects ; blood pressure control
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A multicentre study of 6–10 weeks duration was performed in 60 ambulant hypertensive patients aged over 60 years to compare the efficacy of methyldopa and propranolol with particular reference to the occurrence of cold extremities and sleep disturbances. Blood pressure was effectively controlled by both drugs being reduced from a mean of 180/108 mmHg to 161/93 with methyldopa and 180/108 to 162/94 with propranolol. More patients treated with methyldopa (74%) achieved the target diastolic blood pressure of 95 mmHg or below compared with those treated with propranolol (58%). Side effects were more frequent in the propranolol group necessitating the withdrawal of four patients from the study. Only one patient on methyldopa was withdrawn. The incidence of cold extremities was significantly greater with propranolol. The occurrence of sleep disturbances was similar in both groups. In this group of elderly patients methyldopa was better tolerated than propranolol.
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  • 61
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    European journal of clinical pharmacology 26 (1984), S. 543-547 
    ISSN: 1432-1041
    Keywords: indapamide ; hypertension ; glomerular filtration ; arginine vasopressin ; free water clearance ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Renal plasma flow (RPF), glomerular filtration rate (GFR), arginine vasopressin in plasma (AVP), free water clearance ( $${\text{C}}_{{\text{H}}_{\text{2}} {\text{O}}}$$ ) and blood pressure (BP) were determined in 11 patients with essential hypertension at the end of 3 consecutive periods of observation each of 6 of weeks duration; indapamide 2.5 mg daily was given in period 2 and placebo in periods 1 and 3. RPF and GFR were reduced by 9% and BP by 9%/14% supine and 14%/12% standing during indapamide treatment. Changes in renal haemodynamics were not correlated with those in BP. AVP was not significantly altered by indapamide and was not correlated with BP. Indapamide reduced $${\text{C}}_{{\text{H}}_{\text{2}} {\text{O}}}$$ possibly due to the reduction in GFR. It is concluded that indapamide evidently induces redistribution of the cardiac output, with enhanced muscle blood flow and reduced renal perfussion, and that AVP does not seem to be involved in blood pressure regulation in mild to moderate essential hypertension under basal conditions.
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  • 62
    ISSN: 1432-1041
    Keywords: beta-blockers ; hypertension ; ISA ; CS ; cold extremities
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Patients with essential hypertension were interviewed prior to entering therapeutic studies in general practice. Patients' age, sex and details of antihypertensive therapy (if any) were noted, as were their spontaneously reported symptoms. Complaints of cold extremities were highest in those taking a beta-blocker (4.1%). Those untreated or taking other therapies complained less often. Those patients taking a beta-blocker with ISA complained less often (3.1%) of cold extremities than those taking a beta-blocker without ISA (5.2%).
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  • 63
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    European journal of clinical pharmacology 27 (1984), S. 13-17 
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; blood pressure decrease ; drug combination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The medication of patients receiving hydralazine, captopril and minoxidil was replaced by a new galenical form, long-acting nifedipine. An additional decrease in blood pressure was observed in most of the patients. Renal function was maintained in all of them. Adverse reactions may be reduced by the use of long-acting nifedipine, which would permit a reduction in the dosage of captopril and minoxidil.
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    European journal of clinical pharmacology 27 (1984), S. 23-27 
    ISSN: 1432-1041
    Keywords: hypertension ; alpha2-adrenoceptors ; blood pressure ; clonidine ; guanfacine ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time courses of the changes in plasma growth hormone and noradrenaline concentrations in response to 15 min infusions of clonidine 0.2 mgs and guanfacine 2 mgs, were studied in six normal volunteers, in a double-blind, randomised, crossover study. Plasma noradrenaline fell within 15 min of the commencement of drug administration, by 36±14% after clonidine (p〈0.05) and by 32±11% (p〈0.05) after guanfacine. Plasma growth hormone was not significantly elevated until the 30th minute to 12.0±4.7 lU/ml (p〈0.05) after clonidine and 14.7±11.5 lU/ml (p〈0.05) after guanfacine, having been undetectable prior to both drugs. The reduction in plasma noradrenaline by these α2-adrenergic agonists, prior to activation of central adrenoceptors as detected by changes in plasma growth hormone, is evidence for a peripheral component in their sympatholytic effect.
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  • 65
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    European journal of clinical pharmacology 27 (1984), S. 147-152 
    ISSN: 1432-1041
    Keywords: moxonidine ; clonidine ; hypertension ; double-blind crossover ; side-effects ; withdrawal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of moxonidine·HCl·H2O (MOX) was compared with that of clonidine·HCl (CLON) in a randomized double-blind crossover study in 20 hypertensive outpatients (BP range 154–178/96–108 mmHg). After 2 weeks without antihypertensive medication, either MOX 0.2 mg daily or CLON 0.2 mg daily was given and the dose was titrated until the diastolic blood pressure fell below 90 mmHg. The first treatment period was continued for 2 weeks and, after crossover without a wash-out period, it was followed by the second treatment for a further 2 weeks. Within the first 4 days of administration 0.2–0.4 mg of either agent caused a significant decrease in BP (p〈0.001) from a mean of 166/100 mmHg to 149/86 mmHg after CLON (approx. −10/−14%), and 163/99 mmHg to 146/84 mmHg after MOX (approx. −10/−15%). No significant difference in the fall in BP or pulse rate was detected between the two drugs. In the mean daily dose of 0.3 mg both drugs showed the same antihypertensive activity, but on CLON a higher incidence of side effects (p=0.003) was noted, and after discontinuation of therapy a more rapid rise in BP (systolic BP p〈0.01, diastolic BP p〈0.02) was found. 17 patients on CLON complained of side effects, especially tiredness and dry mouth, whilst only 6 patients on MOX were affected (p=0.003).
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  • 66
    ISSN: 1432-1041
    Keywords: guanfacine ; hydrallazine ; hypertension ; sympathetic nervous activity ; plasma renin activity ; cardiac and systemic haemodynamics ; blood pressure ; limb blood flow ; limb vascular resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of guanfacine and hydrallazine on cardiovascular haemodynamics and on sympathetic nervous activity has been studied in 16 patients with essential hypertension. Two groups of patients were investigated: in Group A guanfacine brought the blood pressure back to normal (diastolic blood pressure ⩽90 mmHg), and in Group B diastolic blood pressure was 〉 90 mmHg and required the addition of hydrallazine. Guanfacine significantly decreased heart rate, plasma renin activity and urinary excretion of noradrenaline, without altering cardiac contractility. In Group B, guanfacine 2 to 6 mg/day produced a significant decrease in blood pressure from 178.7/112.4 to 164.4/102.9 mmHg and in heart rate from 77.1 to 62.7 beats/min after 4 weeks of treatment. Guanfacine did not significantly alter preejection period, cardiac output or total peripheral resistance. Hydrallazine 50 to 300 mg/day caused a further reduction in blood pressure from 164.4/102.9 to 150.7/90.2 mmHg and an increase in heart rate from 62.7 to 72.1 beats/min. Limb blood flow was increased from 4.55 to 5.93 ml/100 g/min and limb vascular resistance was decreased from 39.55 to 23.6 mmHg 100 g·min/ml. Hydrallazine also caused a slight increase in plasma renin activity and urinary excretion of noradrenaline. It is concluded that guanfacine is a useful agent to block a hydrallazine-induced increase in sympathetic nervous activity.
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  • 67
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    European journal of clinical pharmacology 27 (1984), S. 407-414 
    ISSN: 1432-1041
    Keywords: piretanide ; hypertension ; triamterene ; double blind comparison ; potassium ; magnesium ; side-effects ; serum electrolytes ; serum parameters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a randomized, double blind, parallel group study in out patients with mild to moderate essential hypertension the effects of piretanide on serum electrolytes and on blood pressure were compared with those of triamterene alone and the combination piretanide + triamterene. 136 patients entered the study; 18 patients did not fulfill the inclusion criteria (RRdiast was below 95 mmHg or above 120 mmHg) at the end of the placebo period, 6 dropped out due to side effects, and 1 due to lack of efficacy. Data from 1 patient were not evaluated because the patient did not come regularly for checkups. The results for 110 patients were analyzed. Piretanide 6 mg b.d. and piretanide 6 mg + triamterene 50 mg b.d. produced a significant reduction both in supine and erect blood pressure, which was evident at 2 weeks and which increased over the ensuing 12 week trial period. A mean maximal fall of 16.5% was noted in the piretanide group and 15% in the piretanide + triamterene group. Triamterene alone (50 mg b.d.) also reduced diastolic and systolic blood pressures but the reduction was significantly less (diastolic blood pressure) than in both the piretanide groups, and it showed a more rapid return to pretreatment level during a placebo washout phase at the end of the study. A reduction in standing diastolic blood pressure below 95 mmHg was attained in 84% of patients in the piretanide group, 82% in the piretanide + triamterene group and in only 58% of the triamterene group. There were no significant changes within groups nor differences between the three groups in serum potassium or magnesium. 7 patients were withdrawn from the study because of side-effects due to too marked a clinical action (polyuria, orthostatic disorders and hypotension), one from the piretanide group, and the others in the piretanide + triamterene group. One patient in the triamterene group left the study prematurely due to the lack of effect.
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  • 68
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    European journal of clinical pharmacology 27 (1984), S. 529-534 
    ISSN: 1432-1041
    Keywords: beta-adrenoceptor blocking agents ; hypertension ; adverse reactions ; atenolol ; bopindolol ; pindolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The efficacy of once-daily bopindolol, a nonselectiveβ-adrenoceptor blocking agent with partial agonist activity, and of pindolol and atenolol in the treatment of essential hypertension has been compared. 369 patients were investigated in a double-blind parallel-group study. The treatment period was 10 weeks. Blood pressure normalisation (diastolic BP equal to or less than 90 mmHg) was to be achieved by a stepwise increase in the dose of the test drugs, and, if required, by addition of a diuretic. Normalisation of blood pressure was achieved in 71 to 76% of the subjects, with no significant differences between bopindolol, pindolol, and atenolol. Special attention was given to evaluation of side effects by using two methods for registration of all adverse events during the study. A low incidence of drug-induced side effects was observed, with no significant difference between bopindolol, pindolol, and atenolol. There was no evidence of unsuspected adverse reactions due to bopindolol.
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  • 69
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    European journal of clinical pharmacology 21 (1982), S. 389-390 
    ISSN: 1432-1041
    Keywords: nifedipine ; metoprolol ; hypertension ; calcium antagonist ; side effects
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind trial 26 patients with essential hypertension were treated with nifedipine or placebo for 8 weeks, following a 4-week run-in place-bo period in all patients. The daily dosage of nifedipine during this phase was 10mg 3 times daily. Metoprolol was then added to the therapeutic regimen of both groups for a further 12 weeks. Both nifedipine and metoprolol used as mono-therapy caused statistically significant reductions of arterial pressure. The addition of metoprolol to nifedipine tended to reduce blood pressure further, but blood pressures were not significantly lower than during nifedipine mono-therapy. Side-effects were few and only two patients had to be withdrawn during active therapy, one for headaches during nifedipine therapy, and another for asthma during metoprolol treatment. Combined therapy with a beta-adrenoceptor blocking agent, such as metoprolol, and a calcium antagonist with vasodilating properties, such as nifedipine, offers a theoretically interesting approach in the treatment of hypertension, even though the practical outcome in the present study probably suffered from an inadequate dose of nifedipine during the period of combined therapy.
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  • 70
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    European journal of clinical pharmacology 22 (1982), S. 95-99 
    ISSN: 1432-1041
    Keywords: penbutolol ; hypertension ; primary hypertension ; blood pressure response ; plasma concentration
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Penbutolol (Hoe 893 d), a long-acting non-selective beta-adrenoceptor blocking agent, was given once daily to 23 patients with primary hypertension, WHO Stages I–II. The dose (50–100 mg) needed to achieve the therapeutic goal, i.e. supine diastolic BP〈95 mm Hg, was titrated individually. On a daily dose of penbutolol 83±19 mg (mean±SD) blood pressure (BP, mean±SD) fell from 180±21/112±8 mmHg on placebo to 154±25/94±14 mmHg. 18 patients who reached the therapeutic goal (responders) continued in a double blind, cross-over study versus placebo, during which the supine BP fell on average 20/10 mmHg on the same dose of penbutolol, and 2/1 mmHg on placebo. Plasma concentrations (mean±SD) of free 0.10±0.07 µg/ml) and total (2.02±1.39 µg/ml) penbutolol did not differ between responders and nonresponders, and were not correlated with the fall in BP. Side effects were mild and mostly well tolerated. One patient developed dermatitis and another an elevation of liver enzymes.
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    European journal of clinical pharmacology 23 (1982), S. 403-409 
    ISSN: 1432-1041
    Keywords: alpha-2-adrenoceptors ; hypertension ; clonidine ; human platelets ; 3H-yohimbine binding ; receptor regulation ; clonidine withdrawal ; desensitization ; GTP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of clonidine on the number ofα 2-adrenoceptors in human platelet membranes, determined by3H-yohimbine binding, was investigatedin vitro andin vivo. Incubation of platelet membranes with clonidine (1–100 µM) for 16 h at 25 °C led to a concentration-dependent decrease in the number of3H-yohimbine binding sites of 10–25%; the affinity of3H-yohimbine to the sites was not changed (KD approximately 3–4 nM). In such “desensitized” membranes, inhibition of3H-yohimbine binding by clonidine resulted in steep, monophasic displacement curves, which in comparison to the curves from control membranes (IC50 for clonidine 90 nM), were shifted to the right (IC50: 321 nM) and were not affected by 10−4M guanosine-5′-triphosphate (GTP). Treatment of 3 hypertensive patients with clonidine (3×150 µg/d for 7 days) reduced blood pressure and heart rate. Simultaneously, both3H-yohimbine binding sites on platelet membranes and plasma catecholamine levels decreased within three days and remained at a reduced level during treatment. After abrupt cessation of clonidine treatment, blood pressure, heart rate and plasma catecholamines rapidly increased, reaching values after two days similar to or higher than those before treatment.3H-yohimbine binding sites, however, initially decreased further before returning to control values. In platelet membranes derived from hypertensive patients treated with clonidine for at least three weeks, GTP (10−4M) had no influence on inhibition of3H-yohimbine binding by (—)-adrenaline and clonidine. It is concluded that clonidine desensitizesα 2-adrenoceptors in human platelet membranesin vitro andin vivo. An important step in the desensitization process is the uncoupling of receptor occupancy by agonists and adenylate cyclase activity, as indicated by loss of the regulatory activity of GTP on desensitized membranes. The clonidine withdrawal syndrome may be caused by enhanced release of endogenous catecholamines not adequately regulated by presynapticα 2-adrenoceptors, which have become subsensitive after chronic clonidine treatment.
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  • 72
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    European journal of clinical pharmacology 23 (1982), S. 491-494 
    ISSN: 1432-1041
    Keywords: betaxolol ; hypertension ; double-blind trial ; cross-over trial
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Betaxolol is a cardioselective beta-blocker, which has a bioavailability of 90% and a T1/2 of 20 h. A four group, cross-over double-blind trial was conducted to select between betaxolol 20 mg and 40 mg for long term trials. 60 patients were allocated randomly to one of the sequences placebo-20 mg, 20 mg-placebo, placebo-40 mg and 40 mg-placebo, each treatment lasting for 2 weeks. Groups were homogenous for baseline diastolic blood pressure (DBP), age and male/female ratio, and were slightly unbalanced for weight. A two-way ANOVA (3 treatments, 2 sequences) showed no treatment-sequence interaction nor sequence effect. The mean reduction in DBP was 14.2±1.8 mm Hg following 20 mg and 18.0±1.8 following 40 mg betaxolol, and 4.0±1.2 mm Hg during placebo (p〈0.001). Age, weight, baseline DBP and duration of hypertension did not influence the treatment effect. The 95% confidence intervals of the reduction in DBP were 10.4–17.9 for 20 mg and 14.3–21.6 mm Hg for betaxolol 40 mg. Aiming at a mean reduction to 90 mm Hg, betaxolol 20 mg would appear to be adequate in similar patient populations.
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  • 73
    ISSN: 1432-1041
    Keywords: prizidilol ; hypertension ; side effects ; chronic treatment ; antihypertensive effect ; anaemia
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of a new vasodilator with betablocking properties (SK & F 92657) was investigated in 10 patients with mild to moderate essential hypertension. After a mean treatment period of 26,5 weeks (6,5–49 weeks) blood pressure was significantly reduced, from 168±22/106±6 mmHg to 144±19/94±12 mmHg (p〈0.05 and 0.025). The mean dose was 410 mg (100–700 mg). Heart rate decreased slightly from 77±12 to 70±8 beats/min. Plasma renin activity and plasma aldosterone showed only minor changes. Nausea, heavy dreams, facial and hand flushing and mild depression were reported as side effects. In most patients the symptoms disappeared without reduction in the dose. In one patient anaemia developed after 7 weeks and treatment with prizidilol was stopped. A slight but statistically significant decrease in haemoglobin concentration of 1.1±0.6 g/dl was observed in 5 of the 10 patients (p〈0.02). Thus, a mean dose of prizidilol of 410±242 mg/day had a mean blood pressure lowering effect of 24/12 mmHg. In 7 of the 10 patients (70%) diastolic blood pressure could be reduced to 95 mmHg or less. However, the observed haematological side-effects should be carefully monitored in further studies and may limit the clinical use of prizidilol.
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  • 74
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    European journal of clinical pharmacology 22 (1982), S. 379-381 
    ISSN: 1432-1041
    Keywords: propranolol ; hypertension ; elderly patients ; long-acting propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fifteen elderly patients whose hypertension was controlled by conventional propranolol 80 mg twice a day had their medication changed to one capsule of ‘Inderal’ LA1 (160 mg) daily. The blood pressure, heart rate and propranolol concentrations were measured at various time points when the patients were receiving the conventional preparation and these assessments were repeated when the long-acting preparation was administered. Although the heart rate was lower with conventional propranolol than with ‘Inderal’ LA there was no significant difference in the blood pressure levels. The mean peak blood level of propranolol was, however, significantly lower with ‘Inderal’ LA compared with conventional propranolol and occurred later. At 12 h the plasma propranolol levels were higher after ‘Inderal’ LA than following the intake of conventional propranolol (p〈0.01); there was no difference in the plasma levels at 24 h. The area under the concentration time curve was significantly higher on conventional propranolol. Compared with published data, the plasma levels were higher than those in younger patients. ‘Inderal’ LA was well tolerated and side effects were minimal.
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  • 75
    ISSN: 1432-1041
    Keywords: hypertension ; hydrochlorothiazide ; atenolol ; side effects ; therapeutic efficacy
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After screening a local population in the northern part of The Netherlands for hypertension, 119 patients with a diastolic pressure (DP) between 95 and 120 mmHg were randomised and treated either with 50 mg hydrochlorothiazide (n=59) or 100 mg atenolol (n=60). After 1 month of treatment 6 patients in the hydrochlorothiazide group and 24 patients in the atenolol group had reached a DP⩽90 mmHg (p〈0.001). 43 of the 50 non-responders to hydrochlorothiazide were switched to atenolol and 30 of the 35 non-responders to atenolol were changed to hydrochlorothiazide. One month after the switch 19 patients in the atenolol group and 2 patients in the hydrochlorothiazide group had reached a DP⩽90 mmHg (p〈0.001). After 6 months of treatment 32 of the 43 atenolol responders and 7 of the 8 hydrochlorothiazide responders were still receiving the same medication, as their DP was still⩽90 mmHg. Non-responders to either medication were given the combination (n=46). 21 patients now became normotensive as did a further 10 after increasing the dose of atenolol to 200 mg. Thus, in all 70 patients had a blood pressure ⩽90 mmHg after treatment for 4 months. Both drugs induced a significant reduction in the total of number of complaints after 1 month of treatment. They did not differ from each other. The reduction was seen both in responders and non-responders and persisted during treatment for 6 months. It is concluded that in terms of short-term efficacy the cardioselective, hydrophilic beta adrenoceptor-blocking drug atenolol is preferable to hydrochlorothiazide in the treatment of uncomplicated hypertension.
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  • 76
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    European journal of clinical pharmacology 23 (1982), S. 397-401 
    ISSN: 1432-1041
    Keywords: hypertension ; prazosin ; alpha-adrenoceptors ; alpha-blocking drugs ; UK-33,274
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eleven patients with uncomplicated essential hypertension received increasing single daily doses of UK-33,274, a new alpha-1 adrenoceptor antagonist, and prazosin for 4 days, in a open cross-over study. Doses were increased until a satifactory blood pressure response was obtained. Average doses reached were 4.5 mg for UK-33,274 and 2.4 mg for prazosin. The maximum effect of the two drugs on standing blood pressure was similar, but prazosin was more effective in the supine position. Both drugs had a greater effect on standing than on supine blood pressure. UK-33,274 caused a consistent increase in heart rate while prazosin did not. Whereas there was no clear difference between the two compounds in the duration of the reduction in blood pressure the onset of action was more gradual for UK-33,274. The incidence of side-effects was similar for both drugs. The data suggest that UK-33,274 is less effective than prazosin in reducing blood pressure.
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  • 77
    ISSN: 1432-1041
    Keywords: carprazidil ; minoxidil ; hypertension ; catecholamines ; renin ; aldosterone ; blood volume ; hypertrichosis ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The efficacy and side effects of the new vasodilator carprazidil and the established vasodilator minoxidil were compared in 18 hypertensive patients inadequately controlled by 2 to 4 conventional drugs; the latter included diuretics, beta-blockers and/or sympatholytics and, in half the cases, vasodilators, such as hydralazine, diazoxide or the postsynaptic alpha-blocker prazosin. The vasodilators were withdrawn and, using a crossover design all patients received carprazidil (mean final dose 88 mg) and minoxidil (20 mg) for an average period of 5 to 6 months. The effects of the 2 agents appeared to be qualitatively and quantitatively similar. Both tended to cause sodium retention and an increase in heart rate, which required an increased dose of diuretic in one third of the cases or of a beta-blocker in a quarter. With this approach mean body weight and blood volume were not altered in the established phase of carprazidil or minoxidil treatment; heart rate and plasma norepinephrine tended to be only minimally increased, plasma renin was slightly increased, and plasma aldosterone and epinephrine were largely unchanged. Supine and upright blood pressure were reduced from initial values of 189/113 and 167/113 mm Hg, to 149/95 and 138/95 mm Hg (−18 and −17%), respectively, during carprazidil, and to 154/95 and 141/96 mm Hg (−17 and −15%) during minoxidil therapy. Hypertrichosis occurred with both agents in almost all patients, and limits their more prolonged use in females. No adverse side effects on haematological parameters, liver or renal function were observed, nor was antinuclear antibody detected. It is concluded that carprazidil and minoxidil are equivalent vasodilator agents in the treatment of severe hypertension, particularly in males.
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  • 78
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    European journal of clinical pharmacology 26 (1984), S. 603-608 
    ISSN: 1432-1041
    Keywords: pinacidil ; hypertension ; pinacidil pyridine-N-oxide ; urinary excretion ; protein binding ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Preliminary investigation in 3 healthy volunteers suggested that intravenous pinacidil in a dose of 0.2 mg/kg had a potent but well-tolerated hypotensive action in the supine position. Facial flushing, uncomfortable chest sensation and distressing postural hypotension occurred at serum concentrations above 300 ng/ml. Pinacidil, 0.2 mg/kg, was given intravenously over 4 min to 15 healthy volunteers in the supine position. Maximum fall in mean arterial pressure (MAP) was 15.7±6.0 mmHg. Maximum rise in heart rate was 23.8±6.6 beats/min. Pinacidil serum distribution half-life ( $${\text{T}}_{{\raise0.7ex\hbox{${\text{1}}$} \!\mathord{\left/ {\vphantom {{\text{1}} {{\text{2}}\alpha }}}\right.\kern-\nulldelimiterspace}\!\lower0.7ex\hbox{${{\text{2}}\alpha }$}}}$$ ) was 13.4±8.5 min and elimination half-life ( $${\text{T}}_{{\raise0.7ex\hbox{${\text{1}}$} \!\mathord{\left/ {\vphantom {{\text{1}} {{\text{2}}\beta }}}\right.\kern-\nulldelimiterspace}\!\lower0.7ex\hbox{${{\text{2}}\beta }$}}}$$ ) was 2.13±0.49 h. The apparent volume of distribution (Vdβ) was 90.3±13.21 and total body clearance was 31.1±9.61/h. Pinacidil was approximately 40% bound to plasma protein over the concentration range 40–400 ng/ml. Urinary excretion of unchanged pinacidil accounted for 5.7 ± 1.3% of the administered dose over 24 hours and urinary excretion of the major metabolite, pinacidil pyridine-N-oxide, was 31.6±9.2% of the administered dose. It was concluded that intravenous pinacidil is a potent vasodilator hypotensive compound, with a duration of action between 1.5 and 2 h.
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    European journal of clinical pharmacology 26 (1984), S. 661-661 
    ISSN: 1432-1041
    Keywords: endralazine ; hypertension ; elimination half-liefe ; compartment model
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    Topics: Chemistry and Pharmacology , Medicine
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  • 80
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    European journal of clinical pharmacology 27 (1984), S. 13-17 
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; blood pressure decrease ; drug combination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The medication of patients receiving hydralazine, captopril and minoxidil was replaced by a new galenical form, long-acting nifedipine. An additional decrease in blood pressure was observed in most of the patients. Renal function was maintained in all of them. Adverse reactions may be reduced by the use of long-acting nifedipine, which would permit a reduction in the dosage of captopril and minoxidil.
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  • 81
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    European journal of clinical pharmacology 27 (1984), S. 23-27 
    ISSN: 1432-1041
    Keywords: hypertension ; alpha2-adrenoceptors ; blood pressure ; clonidine ; guanfacine ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time courses of the changes in plasma growth hormone and noradrenaline concentrations in response to 15 min infusions of clonidine 0.2 mgs and guanfacine 2 mgs, were studied in six normal volunteers, in a double-blind, randomised, crossover study. Plasma noradrenaline fell within 15 min of the commencement of drug administration, by 36±14% after clonidine (p〈0.05) and by 32±11% (p〈0.05) after guanfacine. Plasma growth hormone was not significantly elevated until the 30th minute to 12.0±4.7 lU/ml (p〈0.05) after clonidine and 14.7±11.5 lU/ml (p〈0.05) after guanfacine, having been undetectable prior to both drugs. The reduction in plasma noradrenaline by these α2-adrenergic agonists, prior to activation of central adrenoceptors as detected by changes in plasma growth hormone, is evidence for a peripheral component in their sympatholytic effect.
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  • 82
    ISSN: 1432-1041
    Keywords: beta-blockers ; hypertension ; ISA ; CS ; cold extremities
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Patients with essential hypertension were interviewed prior to entering therapeutic studies in general practice. Patients’ age, sex and details of antihypertensive therapy (if any) were noted, as were their spontaneously reported symptoms. Complaints of cold extremities were highest in those taking a beta-blocker (4.1%). Those untreated or taking other therapies complained less often. Those patients taking a beta-blocker with ISA complained less often (3.1%) of cold extremities than those taking a beta-blocker without ISA (5.2%).
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  • 83
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    European journal of clinical pharmacology 27 (1984), S. 287-289 
    ISSN: 1432-1041
    Keywords: pinacidil ; hypertension ; vasodilator ; patients ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A new vasodilator drug, pinacidil, N″-cyano-N-4-pyridyl-N′-1, 2,2-trimethylpropylguanidine, was studied in an open trial in 15 patients with moderate to severe hypertension. Four patients received pinacidil monotherapy, and in 11 patients it was used with a diuretic or a beta-blocker. In all but one patient normotension was achieved with a mean daily pinacidil dose of 46.7 mg b.i.d. (range 20–100 mg). Side effects were few and were action-related. There was no evidence of early toxicity. Pinacidil is a promising new antihypertensive vasodilator, which deserves further clinical evaluation.
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  • 84
    ISSN: 1573-4927
    Keywords: aldehyde oxidase ; pyridoxal oxidase ; tissue specificity ; Drosophila
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The substrate specificities of aldehyde and pyridoxal oxidases in Drosophila melanogaster have been determined with a variety of aliphatic and aromatic aldehydes. This analysis has led to the discovery that 2,4,5-trimethoxy-benzaldehyde is a specific substrate for pyridoxal oxidase, as based on the histochemical distribution of oxidase activity, the absence of enzymatic activity in the lpo 1strains, and the dosage dependence on the number of lpo +genes present. The tissue-specific localization of aldehyde oxidase (AO) and pyridoxal oxidase (PO) in the larval and adult structures showed that AO was present in all the major internal organs of the larvae and adults, including brain, imaginal discs, Malpighian tubules, digestive system, and reproductive structures. Pyridoxal oxidase is present in many of the same structures which possess AO, but is missing from the cardia, crop, imaginal discs, ovarian follicle cells, paragonia, pericardial cells, and wreath cells. The only structure which possesses PO but lacks AO is the larval salivary gland. These histochemical differences in AO and PO distribution were also confirmed by enzymatic analysis of the activities present in homogenates of ovaries, paragonia, and salivary glands. The general pattern of enzyme expression appears to be established during embryogenesis and maintained throughout the life of the individual.
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  • 85
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    Biochemical genetics 20 (1982), S. 461-474 
    ISSN: 1573-4927
    Keywords: Drosophila ; allozymes ; α-Gpdh ; selection ; genetic background
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    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Three sets of experiments have been conducted in order to evaluate the role of natural selection at the α-Gpdh locus in Drosophila melanogaster. (1) The evolution of the F-allele frequency has been followed for many generations in 13 experimental populations having different genetic backgrounds. (2) Egg-to-adult viability has been measured in synthetic populations derived from one locality (Brouilly) and the results have been compared with those of a previous experiment involving a different local population (Tostes). (3) The effects of sodium octanoate on egg-to-adult viability have been measured on the genotypes FF, FS, SF, and SS. The results demonstrate that selection operates on a small block of genes which includes the α-Gpdh locus.
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  • 86
    ISSN: 1573-4927
    Keywords: esterase ; duplication ; gene expression ; Drosophila
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    Notes: Abstract An esterase duplication is described in the sibling species pair Drosophila mojavensis and Drosophila arizonensis. We present evidence for two separate structural loci mapping at a distance of less than 0.16 recombination units from each other. Alleles at the two loci have the same substrate specificities and form small amounts of interlocus heterodimers. One locus (Est-5) is functioning throughout the insect's life cycle and appears at high concentrations in the hemolymph and the fat body. Its duplicate (Est-4) functions only during the late larval stage and is concentrated mainly in the carcass. No null alleles at either locus were observed in population surveys. An examination of 12 other species from the repleta group, to which D. mojavensis and D. arizonesis belong, suggests that Est-5 is universally present, but the activity levels of Est-4 vary among species and may be totally absent in some species. Variation in the level of Est-4 activity does not closely follow the phylogenetic relationship.
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  • 87
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    Biochemical genetics 20 (1982), S. 179-198 
    ISSN: 1573-4927
    Keywords: acetylcholinesterase ; Drosophila ; malathion ; insecticide resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The relationship between the 50% survival time for flies feeding on a malathion-containing medium and the activity of acetylcholinesterase (AChE) was determined for 15 isofemale lines of Drosophila melanogaster. A significant correlation was found (r=0.28, P〈0.05), with more resistant lines tending to have a lower level of AChE activity. An association between AChE and malathion resistance was also observed in a selection experiment. The AChE activity decreased in two of two populations selected for malathion resistance. AChE from these populations was altered in kinetic parameters (measured in crude head extracts) and electrophoretic mobility. Although the “resistant” AChE had a lower activity (V m) on either a per milligram protein or a per individual basis, its apparent K m for acetylthiocholine was lower than that of “susceptible” AChE. Recombination mapping of both low activity and fast electrophoretic mobility localized these traits to the region of the structural locus (Ace) on the third chromosome. The AChE activity of flies heterozygous for a variety of Ace lesions (kindly provided by Dr. W. M. Gelbart) was consistent with this location. The changes in AChE were suggested to have been caused by selection of alleles at the Ace locus.
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  • 88
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    Biochemical genetics 22 (1984), S. 153-168 
    ISSN: 1573-4927
    Keywords: alcohol dehydrogenase ; Drosophila ; activity ratio ; specific activity
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    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Thirteen Drosophila Adh variants have been characterized with respect to gene expression, substrate preference, thermostability, and specific activity. The results suggest that the variants may be grouped into two biochemical classes, typified by the properties of the two most common enzyme forms, ADH-F and ADH-S. Membership of these classes cannot be predicted from electrophoretic mobility, nor is any simple classification possible with regard to the characteristics of level of gene expression (in terms of ADH activity or ADH protein) or thermostability of the gene product.
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  • 89
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    Biochemical genetics 22 (1984), S. 1015-1029 
    ISSN: 1573-4927
    Keywords: acetaldehyde ; alcohol dehydrogenase ; aldehyde oxidase ; Drosophila
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Metabolic utilization and toxicity of acetaldehyde were studied in flies lacking alcohol dehydrogenase (ADH), aldehyde oxidase (AO), or both functions. Prior to the experiments, mutant alleles Adh n4 and mal were transferred to the same genetic background by 10 successive backcrosses. By comparison with wild-type flies, various deleterious, pleiotropic effects could be attributed to the mal allele but not to Adh n4 . Of the four genotypes studied (mal, Adh n4 , mal Adh n4 , and wild), all were able to use acetaldehyde as a resource in a similar way. In spite of its high toxicity, acetaldehyde appeared a better resource than ethanol. Flies treated with intermediate acetaldehyde concentrations (around 0.5%) exhibited a very high interindividual heterogeneity which could reflect a physiological adaptation occurring as a consequence of the aldehyde treatment. Toxicity tests showed that ADH-negative flies were more sensitive to acetaldehyde than wild type, but this is most likely explained by the transformation of the aldehyde into alcohol. Our results show that the aldehyde metabolizing enzyme (AME) system in Drosophila is neither ADH nor AO. The existence of an aldehyde dehydrogenase is plausible.
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  • 90
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    Biochemical genetics 20 (1982), S. 407-424 
    ISSN: 1573-4927
    Keywords: dipeptidases ; Drosophila ; variation
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    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Three dipeptidases in Drosophila melanogaster are under independent genetic control and their structural genes have been localized, Dip-A to 2R and Dip-B and Dip-C to 3R (Voelker and Langley, 1978; Ohnishi and Voelker, 1981). These enzymes were characterized with respect to their substrate specificities, genetic variability (electrophoretic mobility and quantitative activity level), ontogeny (activity and isozyme pattern), and tissue localization. The dipeptide substrate specificities of DIP-A and DIP-B overlap each other considerably, but do not overlap with DIP-C. In natural populations, DIP-B and DIP-C are essentially monomorphic electrophoretically whereas DIP-A is polymorphic for three allozymes. Both DIP-A and DIP-B show quantitative genetic variation of activity level within an allozyme class. All three enzymes are expressed at all stages in the life cycle, but DIP-A and DIP-B activities vary considerably according to developmental stage and sex of adult. The tissue localizations of DIP-A and DIP-B activities show similar patterns and a nearly ubiquitous occurrence of both enzymes, but with particularly high values in larval and adult midguts and in the adult female reproductive system. These results suggest a general metabolic role for the enzymes, such as regulation of the concentrated pools of amino acids and oligopeptides found in Drosophila tissues.
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  • 91
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    Journal of chemical ecology 10 (1984), S. 1787-1798 
    ISSN: 1573-1561
    Keywords: Coleoptera ; Curculionidae ; Otiorhynchus sulcatus (F.) ; black vine weevil ; Ericaceae ; Rhododendron ; trichomes ; glandular scales ; essential oils ; volatiles ; plant resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Glandular scales on selected lepidote rhododendron species varied in density from 109 ± 13 to 4180 ± 60/cm2 of leaf surface. Globules contained within the scales stained with Sudan IV, a lipophilic dye. Essential oil contents of the scales varied with species from 24 ± 8 to 151 ± 35 ng/scale. Black vine weevil [(Otiorhynchus sulcatus (F.)] feeding on leaves from a sample of rhododendron species was inversely related to leaf essential oil content, and weevil feeding on membrane filters was inhibited by application of essential oil extracts from leaves of most lepidote rhododendrons tested. Results suggest that the glandular scales of the lepidote rhododendrons function, at least in part, in plant defense against insects.
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  • 92
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    Journal of chemical ecology 10 (1984), S. 723-752 
    ISSN: 1573-1561
    Keywords: Ips typographus ; pheromone ; release ; recapture ; diffusion ; model ; Coleoptera ; Scolytidae ; trap ; marking ; dispersal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The movement of bark beetles near an attractive pheromone source is described in terms of mathematical models of the diffusion type. To test the models, two release experiments involving 47,000 marked spruce bark beetles [Ips typographus (L.)] were performed. The attractive source was a pheromone trap, surrounded by eight concentric rings with eight passive trap stations on each ring. Captures were recorded every 2–10 minutes for the pheromone trap and once for the passive traps. The models were fitted to the distribution in time of the central pheromone trap catch and to the spatial distribution of catch among the passive traps. The first model that gives a reasonable fit consists of two phases: Phase one—After release the beetles move according to a diffusion process with drift towards the pheromone trap. The strength of the drift is inversely proportional to the distance from the traps. Phase two—those beetles attracted to, but not caught by, the pheromone trap are no longer influenced by the pheromone, and their movement is described by a diffusion process without drift. In phase two we work with a loss of beetles, whereas the experiment seems to indicate that the loss of beetles in phase one is negligible. As a second model, the following modification of phase one is considered: After release the beetles move according to a diffusion process without drift, until they start responding to the pheromone (with constant probability per unit time), whereafter they start moving according to a diffusion process with drift. This study, like other release experiments, shows that the efficiency of the pheromone trap is rather low. What is specific for the present investigation is that we try to explain this low efficiency in terms of dynamic models for insect movement. Two factors seem to contribute: Some beetles do not respond to pheromone at all, and some beetles disappear again after having been close to the pheromone trap. It also seems that the motility of the beetles decreased after they ceased responding to the pheromone. Furthermore, the data lend some support to the hypothesis that flight exercise increases the response of the beetles to pheromone.
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  • 93
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    Journal of chemical ecology 10 (1984), S. 759-769 
    ISSN: 1573-1561
    Keywords: Ips typographus ; Dendroctonus micans ; Coleoptera ; Scolytidae ; exo-brevicomin ; (+)-ipsdienol ; single-cell recordings ; interspecific attraction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Olfactory receptor cells were studied electrophysiologically inIps typographus andDendroctonus micans. The investigation revealed cells which were keyed to pheromone compounds characteristic of the reciprocal genus. Thus, cells keyed toexo-brevicomin were found inI. typographus, whereas cells keyed to (+)-ipsdienol were present inD. micans. Laboratory behavioral tests indicated an attractive effect of the two compounds on beetles of the reciprocal genus. InI. typographus the effect ofexo-brevicomin predominantly concerned males and enhanced their response to the pheromone “ipslure.” It is suggested thatexo-brevicomin serves as an interspecific attractant forI. typographus, which may be guided by pheromone compounds of the reciprocal genus in finding suitable breeding material. The function of (+)-ipsdienol inD. micans is more uncertain. It may be either a pheromone or an interspecific messenger.
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  • 94
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    Journal of chemical ecology 10 (1984), S. 1759-1785 
    ISSN: 1573-1561
    Keywords: Cotton boll weevil ; Anthonomus grandis ; Coleoptera ; Curculionidae ; pheromone ; kairomone ; plant odor ; olfaction ; electroantennogram ; attractant ; host plant ; green leaf volatiles
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Electroantennogram (EAG) techniques were utilized to measure the antennal olfactory responsiveness of adult boll weevils,Anthonomus grandis Boh. (Coleoptera: Curculionidae), to 38 odorants, including both insect and host plant (Gossypium hirsutum L.) volatiles. EAGs of both sexes were indicative of at least two receptor populations: one receptor population primarily responsive to pheromone components and related compounds, the other receptor population primarily responsive to plant odors. Similar responses to male aggregation pheromone components (i.e., compounds I, II, and III + IV) were obtained from both sexes, but females were slightly more sensitive to I. Both sexes were highly responsive to components of the “green leaf volatile complex,” especially the six-carbon saturated and monounsaturated primary alcohols. Heptanal was the most active aldehyde tested. More acceptors responded to oxygenated monoterpenes than to monoterpene hydrocarbons. β-Bisabolol, the major volatile of cotton, was the most active sesquiterpene. In general, males, which are responsible for host selection and pheromone production, were more sensitive to plant odors than were females. In fact, males were as sensitive to β-bisabolol and heptanal as to aggregation pheromone components. Electrophysiological data are discussed with regard to the role of insect and host plant volatiles in host selection and aggregation behavior of the boll weevil.
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  • 95
    ISSN: 1573-1561
    Keywords: Ips typographus ; spruce bark beetle ; Coleoptera ; Scolytidae ; 2-methyl-3-buten-2-ol ; ipsenol ; cis-verbenol ; ipsdienol ; trans-verbenol ; verbenone ; myrtenol ; trans-myrtanol ; 2-phenylethanol ; ß-isophorone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Ips typographus beetles were collected in the field, separated into eight attack phases (from beetles walking on the trunk of a tree under attack to those excavating gallery systems with a mother gallery longer than 4 cm), and immediately frozen in liquid nitrogen. 2-Methyl-3-buten-2-ol,cis- andtrans-verbenol, verbenone, myrtenol, trans-myrtanol, ipsenol, ipsdienol, and 2-phenylethanol were quantified from excised hindguts against an internal standard, heptyl acetate, in the extraction solvent. Methylbutenol, the pinene alcohols, and 2-phenylethanol showed the same pattern of variation between attack phases in males, with the largest amounts present before accepting females and then a fast decline. Ipsenol and ipsdienol were not detected in males before the females were accepted, and the amounts increased when the females start their egg laying. Verbenone occurred only in trace amounts. The beetles were sampled from five Norway spruce trees (Picea abies) of differing resin flow. The correlations between the nine pheromone components and five major host monoterpenes in the gut showed that the variation in the amount of methyl-butenol, ipsenol, and ipsdienol could not be explained by the variation in the amounts of host monoterpenes. In contrast over 80% of the quantitative variation ofcis-verbenol,trans-verbenol, and myrtenol was explained by the amount of α-pinene. The nine pheromone components from 36 individual males were also quantified. Both methylbutenol andcis-verbenol showed a large variation in both amounts and proportions. Females containedtrans-verbenol and traces of most other components found in males. When accepted by the male, they also contained a female-specific compound, β-isophorone. Behavioral and biosynthetic implications of the results are discussed.
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  • 96
    ISSN: 1573-1561
    Keywords: Coleoptera ; Scolytidae ; Scolytus multistriatus ; pheromone ; insect olfaction ; electroantennogram ; electrophysiology ; differential adaptation ; multistriatin ; 4-methyl-3-heptanol ; α-cubebene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Electroantennograms were recorded fromScolytus multistriatus in response to 4-methyl-3-heptanol, the four geometric isomers of multistriatin, and cubeb oil. Charateristic dose-response curves for response amplitude and the time required for the voltage trace to return to 1/2 baseline (recovery rate) were established. Recovery rates were significantly more rapid following stimulation with 4-methyl-3-heptanol or cubeb oil than with the multistriatin isomers. At most intensities, α-multistriatin, the isomer that evokes behavioral response, gave significantly larger EAGs with significantly longer recovery rates than the other isomers. Results of differential adaptation experiments suggested that 4-methyl-3-heptanol interacted with the processes involving multistriatin and cubeb oil activity. However, cross-activity of acceptors for these compounds seems unlikely; single sensillum recordings are needed to ascertain the response spectra for individual receptor neurons.
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  • 97
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    Journal of chemical ecology 8 (1982), S. 1399-1409 
    ISSN: 1573-1561
    Keywords: Coleoptera ; Scolytidae ; Dendroctonus ponderosae ; pheromone ; frontalin ; exo-brevicomin ; Pinns contorta ; Pinus ponderosa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Frontalin andexo-brevicomin were identified by GC-MS in air drawn over maleDendroclonus ponderosae Hopk. (MPB) from Oregon that had joined females for 1–2 days in the bark of lodgepole and ponderosa pine logs. Unfed males releasedexo- andendo-brevicomin but not frontalin. These three compounds were not detected in either unfed or fed females. Arrestment of males bytrans-verbenol and terpenes in an olfactory walkway was reduced by the addition of racemic frontalin; production of attractant chirps also diminished. Racemic frontalin also strongly reduced the aggregation of MPB in lodgepole and ponderosa pine stands to sticky traps baited with the aggregation pheromonetrans-verbenol and host terpenes; however, the function of the natural enantiomer of frontalin in MPB is unknown.
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  • 98
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    Journal of chemical ecology 8 (1982), S. 1411-1420 
    ISSN: 1573-1561
    Keywords: Coleoptera ; Staphylinidae ; Oxytelinae ; defensive secretion ; glands ; acetates ; lactones ; alkenes ; quinones ; citral
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The secretions of the abdominal glands ofBledius spectabilis Kraatz,Platystethus arenarius Fourcr., andOxytelus piceus L. have been shown to contain four 1-alkenes; toluquinone; toluhydroquinone; C10 −-,C11 −, C12 −-, and C14 − γ-lactones; C12-δ-lactone; citral; and decyl-, undecyl-, and dodecyl acetates. Quantitative results indicate that 1-alkenes are formed probably from present lactones by decarboxylation. According to the known life histories of the beetles, it is suggested that the gland material is not used as an algal growth regulator but represents a unique defensive blend characteristic for the whole subfamily.
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  • 99
    ISSN: 1573-1561
    Keywords: Red flour beetle ; Tribolium castaneum ; Coleoptera ; Tenebrionidae ; food volatiles ; olfactory responses ; olfactometer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Olfactory responses of 72- to 96-hr-old, 24-hr starved adult male, female, or mixed-sex groups of the red flour beetle,Tribolium castaneum (Herbst), to volatiles from wheat and millet kernels, certain milled fractions, and solvent extracts were recorded by using a lightsensitive apparatus. Wheat-germ volatiles from intact germ or solvent extracts were generally more attractive than volatiles of wheat endosperm or wheat bran. Volatiles of whole wheat kernels were the least attractive among test materials of wheat origin, whereas there were no significant differences among whole wheat flour, germ, and endosperm. Wheat-germ extracts, however, were more attractive than were extracts of the other fractions. Whole millet flour or fermented millet flour volatiles were more attractive than those from whole millet kernels or millet starch. Beetles reached maximum responsiveness to grain volatiles by 72–96 hr after adult ecdysis. Groups of virgin female beetles generally were more responsive than male or mixed-sex groups to volatiles of substances tested.
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  • 100
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    Journal of chemical ecology 8 (1982), S. 373-378 
    ISSN: 1573-1561
    Keywords: Dendroctonus frontalis ; Ips calligraphus ; I. grandicollis ; I. avulsus ; Coleoptera ; Scolytidae ; mating ; attraction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Catches ofDendroctonus frontalis andIps avulsus on traps surrounding bolts infested with both sexes of each species in the gallery were not significantly different from catches at bolts infested only with the sex which normally pioneers the host colonization process. In contrast, the presence of the second sex in the gallery significantly reduced catches ofI. grandicollis andI. calligraphus and, additionally, the presence of females in the male galleries ofI. calligraphus significantly reduced the catch ofI. avulsus females as compared with their response to bolts infested with the maleI. calligraphus only.
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