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  • 1
    ISSN: 1432-1041
    Keywords: benzodiazepine ; Chile ; agent consumption/ — utilization ; diazepam ; flunitrazepam
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The consumption of benzodiazepine drugs (BDZ) in Chile in the period 1982–1986 has been studied by the DDD method. National use was assessed using drug import forms as a source of information, assuming that the total amount imported was manufactured and consumed in the same year. The utilization did not show a constant pattern, being 32.7, 33.6, 50.2, 34.9, and 31.3 DDD 1000 per inhabitants per day in 1982, 1983, 1984, 1985 and 1986, respectively. During the study period, diazepam was the most commonly used agent amongst anxiolytic BDZ, reaching a peak of 27.1 DDD per 1000 inhabitants per day in 1984, and flunitrazepam was the most popular hypnotic, attaining its maximum in 1986 (6.4 DDD per 1000 inhabitants per day). The use of BDZ at community pharmacy level was also evaluated, employing the International Marketing System (IMS) as the source of information. At that level the pattern of utilization showed a constant increase during the study period, being 14.9 and 25.8 DDD/1000 inhabitants/per day in 1982 and 1986, respectively. In community pharmacies the anxiolytic BDZ most often consumed was diazepam (maximum 9.1 DDD per 1000 inhabitants per day in 1985), and the commonest hypnotic was flunitrazepam (peak 6.0 DDD per 1000 inhabitants per day in 1986). National consumption of BDZ appeared higher and more variable than use at the community pharmacy level, but in both there was greater usage of anxiolytic than of hypnotic BDZ, and diazepam and flunitrazepam were the most popular agents.
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  • 2
    ISSN: 1432-1041
    Keywords: human insulin ; diabetes control ; blood glucose ; free insulin ; biosynthetic insulin ; semisynthetic insulin ; monocomponent insulin ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen hospitalized insulin requiring diabetics treated with a single daily subcutaneous injection were randomly allocated either to a mixture of porcine Actrapid+Lente MC or a mixture of Regular+NPH—Biosynthetic human insulin (Study 1). In Study 2, 10 patients receiving two daily insulin injections were treated at random with either porcine Actrapid+Monotard, or Actrapid+Monotard—Semisynthetic human insulin or Regular+NPH—Biosynthetic human insulin. Once an optimal insulin regimen was obtained, circadian blood glucose and plasma free insulin profiles (7–9 time points) were determined with the two (Study 1) or three (Study 2) insulin preparations, keeping the doses of insulin constant. In Study 1 no significant difference in blood glucose (BG) or plasma free insulin (FIRI) profiles was observed. The mean daily blood glucose, the mean amplitude of glycaemic excursions (MAGE), the index of blood glucose control (M-value of Schlichtkrull), as well as the post-breakfast increases in blood glucose and mean free IRI, were similar with both types of insulin. In Study 2, BG and FIRI profiles were also similar, except for a significantly lower (p〈0.02) BG at 8.30 p.m. with both human insulins. No significant differences were found in free IRI at that time. Mean BG, M index, MAGE and mean FIRI were similar but the postbreakfast increase was significantly smaller with SHI. In conclusion, the pharmacokinetics of animal monocomponent, semisynthetic and biosynthetic human insulin appear similar, but evening BG control was better with both types of human insulins given twice daily.
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  • 3
    ISSN: 1420-9071
    Keywords: Goldblatt two-kidney one clip hypertension ; methimazole ; hypothyroidism ; relative cardiac hypertrophy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The effects of methimazole, and antithyroid drug, on blood pressure and other parameters were evaluated in the established phase of Goldblatt two-kidney one clip (G2K-1C) hypertension. Methimazole was administered via drinking water for five weeks, starting five weeks after hypertension had been induced. After this period of treatment, similarly high blood pressures were observed in methimazole-treated and non-treated G2K-1C rats, despite the fact that a hypothyroid state had been achieved in methimazole-treated rats. Methimazole-treated G2K-1C rats showed reductions in heart rate, ventricular weight, ventricular/body weight ratio and mortality in comparison with rats not treated with methimazole. These results clearly demonstrate that hypothyroidism induced by methimazole: a) does not reverse G2K-1C hypertension, but b) improves the rate of survival and c) reduces relative cardiac hypertrophy, possibly by the reduction in cardiac work observed in Goldblatt hypothyroid rats.
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  • 4
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A dissociation between inhibition of RNA synthesis and cell lysis was observed when thymocytes of adrenalectomized rats were incubated with high concentrations of pregn-4-ene-11β-ol-3, 20-dione and pregna-1,4-diene-11β-ol-3,20-dione. In contrast, no dissociation of these effects was found with the typical glucocorticoids cortisol and corticosterone, nor with their 1,4-diene analogs under the same conditions.
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  • 5
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In the isolated perfused rat pancreas, omission of extracellular phosphate (H2PO 4 − significantly reduces the insulin secretion in response to 16.7 mM glucose.
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  • 6
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We have identified a minor hemoglobin component (∼5%) in the blood of a healthy Costa Rican female, but not in her mother and two brothers (father not studied), that has an His→Arg replacement at position β77 (Hb Costa Rica). No other amino acid replacements were observed and no β- or γ-chain-like peptides were present. Hb Costa Rica has a normal stability. Sequence analyses of numerous polymerase chain reaction (PCR)-amplified segments of DNA that contain exon 2 of the β gene failed to identify a CAC→CGC (His→Arg) mutation. The same was the case when cDNA was sequenced, indicating that a β-Costa Rica-mRNA could not be detected with this procedure. Gene mapping of genomic DNA with BglII, BamHI, and HindIII gave normal fragments only and with the same intensity as observed for the fragments of a normal control. The quantities of the β chain variants Hb J-Iran and Hb Fukuyama with related mutations at β77 vary between 30% and 45% in heterozygotes, whereas that of Hb F-Kennestone with the same His→Arg mutation but in the Gγ-globin gene, is a high 40%–45% (as percentage of total Gγ) in a heterozygous newborn. These different observations exclude a heterozygosity of the A→G mutation at codon β77, as well as a deletion comparable to that of Hbs Lepore or Kenya, or a β-globin gene duplication, and point to a nontraditional inheritance of Hb Costa Rica. Allele-specific amplification of cDNA with appropriate primers identified the presence of a low level of mutated mRNA in the reticulocytes of the patient, which was confirmed by dotblot analysis of the same material with 32P-labeled probes. Comparable amplification products were not observed in genomic DNA. The A→G mutation apparently occurred in a somatic cell at a relatively early stage in the development of the hematopoietic cell system, and Hb Costa Rica accumulated through rapid cell divisions in patchy areas in the bone marrow (somatic mosaicism). An unequal distribution of Hb Costa Rica over the red cells supports this possibility.
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  • 7
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We have identified a minor hemoglobin component (∼5%) in the blood of a healthy Costa Rican female, but not in her mother and two brothers (father not studied), that has an His→Arg replacement at position β77 (Hb Costa Rica). No other amino acid replacements were observed and no β- or γ-chain-like peptides were present. Hb Costa Rica has a normal stability. Sequence analyses of numerous polymerase chain reaction (PCR)-amplified segments of DNA that contain exon 2 of the β gene failed to identify a CAC→WGC (His→Arg) mutation. The same was the case when cDNA was sequenced, indicating that a β-Costa Rica-mRNA could not be detected with this procedure. Gene mapping of genomic DNA withBglII,BamHI, andHindIII gave normal fragments only and with the same intensity as observed for the fragments of a normal control. The quantities of the β chain variants Hb JIran and Hb Fukuyama with related mutations at (β77 vary between 30% and 45% in heterozygotes, whereas that of Hb F-Kennestone with the same His→Arg mutation but in theGyγ-globin gene, is a high 40%–45% (as percentage of totalGγ) in a heterozygous newborn. These different observations exclude a heterozygosity of the A→G mutation at codon β77, as well as a deletion comparable to that of Hbs Lepore or Kenya, or a β-globin gene duplication, and point to a nontraditional inheritance of Hb Costa Rica. Allele-specific amplification of cDNA with appropriate primers identified the presence of a low level of mutated mRNA in the reticulocytes of the patient, which was confirmed by dotblot analysis of the same material with32p-labeled probes. Comparable amplification products were not observed in genomic DNA. The A→G mutation apparently occurred in a somatic cell at a relatively early stage in the development of the hematopoietic cell system, and Hb Costa Rica accumulated through rapid cell divisions in patchy areas in the bone marrow (somatic mosaicism). An unequal distribution of Hb Costa Rica over the red cells supports this possibility.
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  • 8
    ISSN: 1573-4919
    Keywords: cholesterogenesis ; phenylketonuria ; HMG-CoA reductase ; MVAPP decarboxylase ; phenylalanine-derivatives
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Phenylalanine, phenylpyruvate and phenylacetate produced a considerable inhibition of chick liver mevalonate 5-pyrophosphate decarboxylase while mevalonate kinase and mevalonate 5-phosphate kinase were not significantly affected. Phenolic derivatives of phenylalanine produced a similar inhibition of decarboxylase activity than that found in the presence of phenyl metabolites. The degree of inhibition was progressive with increasing concentrations of inhibitors (1.25–5.00 mM). Simultaneous supplementation of different metabolites in conditions similar to those in experimental phenylketonuria (0.25 mM each) produced a clear inhibition of liver decarboxylase and 3-hydroxy-3-methylglutaryl-CoA reductase. To our knowledge, this is the first report on the in vitro inhibition of both liver regulatory enzymes of cholesterogenesis in phenylketonuria-like conditions. Our results show a lower inhibition of decarboxylase than that of reductase but suggest an important regulatory role of decarboxylase in cholesterol synthesis.
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  • 9
    ISSN: 1572-817X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Electrical Engineering, Measurement and Control Technology , Physics
    Notes: Abstract Experimental observations of 1D and 2D self-focusing in a BaTiO3 crystal under externally DC applied electric field are reported. Stationary self-focusing behaviour can be obtained with and without additional uniform illumination.
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  • 10
    ISSN: 1436-5073
    Keywords: solid-phase spectrophotometry ; derivative spectrophotometry ; pyrocatechol violet ; tungsten determination ; natural and industrial waters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Derivative spectrophotometry was applied to solid-phase spectrophotometry in order to enhance its sensitivity and remove the large background caused by the absorbance of the resin layer. Determination of micro-amounts of tungsten with pyrocatechol violet to form a 2∶1 green complex in acid medium which is fixed on a dextran-type anion-exchange resin (Sephadex QAEA-25) is described as an example for the application of this technique. The absorbance of the resin packed in a 1-mm spectrophotometric cell, was measured directly. The characteristic peak amplitude of the signal at 674 nm in the first-derivative spectrum is useful for quantitative determination of tungsten (3–16 μg 1−1; RSD 5.8%) in natural and industrial water samples.
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