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  • Immunocytochemistry  (69)
  • bioavailability  (65)
  • Springer  (134)
  • American Institute of Physics (AIP)
  • American Meteorological Society (AMS)
  • Nature Publishing Group
  • 1975-1979  (134)
Collection
Publisher
  • Springer  (134)
  • American Institute of Physics (AIP)
  • American Meteorological Society (AMS)
  • Nature Publishing Group
Years
Year
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 16 (1979), S. 211-215 
    ISSN: 1432-1041
    Keywords: fluoride ; bioavailability ; calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of milk products on the gastrointestinal absorption of fluoride from sodium fluoride tablets was studied in five healthy subjects. Two different diets were tested: (1) 250 ml standardized milk (3% fat) and (2) 500 ml of milk, 3 pieces of white bread with cheese and 150 ml of yoghurt. The 100% bioavailability of sodium fluoride tablets during fasting was greatly decreased by coadministration of milk products: with Diet 1 the absolute bioavailability calculated from combined plasma and urine data was in the range 50–79% and with Diet 2 it ranged from 50–71%. It is suggested that the decreased bioavailability produced by dairy products should be taken into account when establishing fluoride dosage regimens for prophylaxis of caries.
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  • 2
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    European journal of clinical pharmacology 16 (1979), S. 417-421 
    ISSN: 1432-1041
    Keywords: theophylline ; aminophylline ; bioavailability ; rapidly dissolving tablet
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of a rapidly dissolving tablet of theophylline and three brands of standard aminophylline tablets was estimated in a four way cross-over study involving 8 healthy adult volunteers. The relative extent of bioavailability as assessed by the measurement of the total area under the plasma concentration time curves showed no difference between the products (P〉0.05). Computed estimates of the rate of drug absorption were similar for all 4 products tested. The results indicate that the rapidly dissolving tablet offers no advantage in respect to rate and extent of absorption over conventional aminophylline tablets.
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  • 3
    ISSN: 1432-1041
    Keywords: chlorthalidone ; pharmacokinetics ; oral and i.v. doses ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seven normal human volunteers each received a constant-rate infusion of chlorthalidone for 2 h, and the same (commonly 50 mg) single oral dose on separate occasions. The concentration of unchanged chlorthalidone was analyzed over a 100 to 220 h period in plasma, red blood cells, urine and faeces after both dosage forms. A three compartment model was required to describe the intravenous plasma concentrations in five of the subjects. A two compartment model sufficed to account for the decay of the oral plasma concentrations in all seven subjects. The mean plasma t1/2 after i.v. dosing was 36.5 h (±10.5 SD), and the mean plasma t1/2 after oral doses was 44.1 h (±9.6 SD). The mean red blood cell concentration t1/2 after i.v. doses was 46.4 h (±9.9 SD), and the mean red blood cell t1/2 after the oral doses was 52.7 h (±9.0 SD). The shorter i.v. half-live was not equally manifest in all subjects, being mainly apparent in three of them. In all cases the urinary excretion rate plots were parallel to the plasma concentration curves. As the faster decay after i.v. administration was not accompanied by increased renal clearance, the difference must have been due to non-renal mechanism. The mean total of 65.4 (±8.6 SD) % of the intravenous dose was excreted in urine over infinite time, whereas the mean total excretion after the oral dose was 43.8 (±8.5 SD) %. Faecal excretion ranged from 1.3–8.5% of dose in the i.v. study to 17.5–31.2% of dose in the oral study. The sum of the amounts present in urine plus faeces pointed strongly to an important metabolic route of elimination of chlorthalidone. Bioavailability estimates (F) from three sets of data were — a mean F of 0.61 from plasma concentrations, 0.67 from urinary excretion measurements and 0.72 from the erythrocyte concentrations. Simulations with a non-linear model indicated lesser validity of the estimate from erythrocyte concentrations. It was concluded that the average of plasma and urine data, F=0.64, yielded the best estimate of the oral availability of chlorthalidone 50 mg in man.
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  • 4
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    European journal of clinical pharmacology 16 (1979), S. 31-38 
    ISSN: 1432-1041
    Keywords: bezafibrate ; hyperlipoproteinemia ; bioavailability ; pharmacokinetics ; GC-MS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition kinetics of bezafibrate, a newly developed drug of great lipid-lowering potency, were investigated in normal male subjects. Five male volunteers received14C-labelled bezafibrate orally in solution, and a further 10 were given the same dose (300 mg) of un-labelled drug as tablets. The concentration of bezafibrate in serum and urine from the latter was determined by GC, and in the former total radioactivity in serum, urine and feces was followed for 48 h, and urinary excretion products were analysed by TLC and GC-MS. Rapid absorption from the gastrointestinal tract led to peak serum levels 30 min and 2 h after administration of solution and tablets, respectively. Since approximately 95% of the administered14C-bezafibrate was excreted in urine within 48 h, and almost all the remainder was detected in feces, absorption can be regarded as complete after administration in solution. The relative optimal bioavailability from the tablets was also complete, since in both cases approximately 50% of the administered dose was detected as unchanged bezafibrate in urine within 24 h by GC in the tablet study, and by TLC in the solution study. Of the decomposition products, more than 20% of the dose was present as glucuronides and the remainder consisted of several more polar compounds, one of which was identified as a hydroxyderivative of bezafibrate. Since the apparent halflife of bezafibrate in serum was 2.1 h, this new drug possesses favourable pharmacokinetic features: rapid and complete absorption, even from tablets, combined with a conveniently short half-life, and clearance which is half renal (56 ml/min) and half metabolic (43 ml/min), giving a total clearance of 99 ml/min.
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  • 5
    ISSN: 1432-1041
    Keywords: indobufen ; platelet aggregation ; single dose ; bioavailability ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six healthy volunteers received single iv and oral doses of 2-[p-(1-oxo-2-isoindolinyl)phenyl] butyric acid 100 mg (indobufen; K 3920), an inhibitor of platelet aggregation. Plasma levels and urinary excretion of the drug were determined by GLC. Collagen-induced platelet aggregation was assessed turbidimetrically at various intervals after administration. The plasma half-life of the drug was 7–8 h and more than 70% of the administered dose was recovered within 48 h in urine, as unchanged drug and as the glucuronide of indobufen. After oral administration of tablets of two different formulations, the drug was completely absorbed, but one formulation showed faster absorption. The maximal inhibitory effect on platelet aggregation was observed 1 to 4 h after iv administration, and it had decreased by 8 h. After tablets, peak effect and the time of the peak were similar, but activity was significantly prolonged, in accordance with the higher plasma levels found at 8 h. The data suggest that the effect of indobufen on platelets is reversible, and that for this drug platelets behave as a compartment that slowly equilibrates with plasma.
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  • 6
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    European journal of clinical pharmacology 16 (1979), S. 45-48 
    ISSN: 1432-1041
    Keywords: quinidine ; slow release formulation ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of quinidine in two sustained release preparations A and B has been compared in three females and three males with i.v. administration of quinidine. The initial rate of oral absorption did not differ between the two drug preparations; the peak concentration was observed after 4 h both for A and B, but was significantly higher after B. A slower decrease in plasma concentration was observed after preparation A than B. Absolute bioavailability did not differ significantly between A (median value 78.4%) and B (median 87.1%). Drug absorption in vivo was in good agreement with the results of in vitro dissolution tests on both preparations. The slower decrease in plasma concentration found for the new sustained release form of quinidine should be of clinical advantage.
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  • 7
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    European journal of clinical pharmacology 16 (1979), S. 335-340 
    ISSN: 1432-1041
    Keywords: cimetidine ; enterohepatic circulation ; irregular absorption ; bioavailability ; pharmacokinetics ; volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability and pharmacokinetics of cimetidine have been studied in healthy volunteers after administration of single intravenous (100 mg) and oral doses (100, 400 and 800 mg). After i.v. administration, the kinetics of cimetidine could be described by a linear, two compartment open model. Substantial variation in half-life was observed between subjects, with a mean value of 2.1 h (range 0.9–4.7). Cimetidine had a low hepatic extraction ratio and a high total plasma clearance, due to extensive urinary excretion of unchanged drug. After oral administration, the plasma concentration vs time curves in most subjects exhibited two marked peaks, an observation that seemed to be constant within individuals and was independent of dose. Bioavailability, estimated as the area under the plasma concentration vs time curves (AUC), after oral doses as compared to the intravenous dose, in most cases exceeded 100%. There was no correlation between bioavailability estimated as AUC and as urinary excretion of unchanged drug. These observations may indicate an enterohepatic circulatory mechanism, predominantly after oral administration. Both unchanged drug and its sulphoxide metabolite appear to be excreted in bile. The latter was shown in vitro to be reduced to cimetidine by fecal bacteria.
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  • 8
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    European journal of clinical pharmacology 15 (1979), S. 269-274 
    ISSN: 1432-1041
    Keywords: phenytoin ; food-intake ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of food intake on the absorption of phenytoin was examined in eight healthy volunteers, by study of single-dose kinetics following ingestion of phenytoin 300 mg either with a standardized breakfast or on an empty stomach. Blood samples were collected at regular intervals from 0 to 48 h, and serum concentrations of unmetabolized phenytoin were determined by gas chromatography. Serum concentrations of the major metabolite of phenytoin, 4-hydroxyphenytoin, were measured by mass fragmentography. Concurrent intake of food and phenytoin appeared to accelerate absorption of the drug from the formulation used, and the peak concentrations were significantly higher (mean increase 40%) in the postprandial than in the preprandial state. As reflected by the AUC (area under the curve), the amount of drug absorbed was increased during postprandial conditions, although the difference only reached borderline significance. It is suggested that phenytoin should always be taken in a defined relation to meals.
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  • 9
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    European journal of clinical pharmacology 16 (1979), S. 107-112 
    ISSN: 1432-1041
    Keywords: quinidine ; enteric-coated tablets ; bioavailability ; gastric emptying ; pH
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of quinidine from single and multiple doses of an enteric-coated preparation (Systodin®) was studied in seven healthy subjects, and was compared with the pharmacokinetics of intravenously administered quinidine and the results of in vitro dissolution tests of the tablets. Absorption of quinidine began after a variable delay, 2–8 h (mean 4.8) after fasting and 3–10 h (mean 6.1) after food. The rate of absorption varied both in and between individuals. It appeared to be lower when the drug was administered after food. Multiple doses after food gave a pattern of plasma concentration-time curves similar to that found on administration of single doses after food. The delay prior to absorption was prolonged at night. The ratio between the maximum and minimum concentration of quinidine during a dose interval varied from 1.3 to 3.2 (mean 2.0). Bioavailability of quinidine in fasting subjects ranged from 69 to 95% (mean 83); variation was greater when doses were administered after food. The release of quinidine from the enteric-coated preparation was pH dependent and was sustained at low pHs as may be found in the intestines. The results indicate that the absorption of quinidine from the enteric-coated formulation was dependent on the highly variable rate of gastric emptying and the pH of intestinal fluid, and it varied greatly both within and between individuals.
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  • 10
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    European journal of clinical pharmacology 16 (1979), S. 141-147 
    ISSN: 1432-1041
    Keywords: prazepam ; N-desmethyldiazepam ; bioavailability ; pharmokinetics ; electron-capture gasliquid chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An original electron-capture gas chromatographic assay was developed for simultaneous measurement of plasma levels of the benzodiazepine derivative prazepam and of its principal unconjugated metabolite, N-desmethyldiazepam. The assay was used to study the pharmacokinetics of the drug and its comparative bioavailability from tablets and from a specially prepared solution. Nine healthy adult volunteers were studied. Each volunteer on one occasion took 30 mg of the drug in tablet form, and on another occasion 30 mg of the drug in solution. In all subjects, N-desmethyldiazepam appeared in plasma shortly after prazepam appeared and reached a peak within four hours of prazepam ingestion. Thereafter plasma N-desmethyldiazepam levels were much higher than plasma prazepam levels throughout. Prazepam became undetectable within six hours of intake, whereas its metabolite could still be measured in plasma fourteen days after dosage. Thus much of the pharmacological action of prazepam may be mediated through its metabolite, N-desmethyldiazepam. In five of the nine subjects, areas under the plasma level curves for the metabolite were not markedly different for the tablet and solution formulations studied. In the other four subjects the area under the curve for the tablets was 50% to 80% of the area under the curve for the solution. The time to reach peak plasma level for the metabolite was shorter after the solution formulation (mean 2.0±SD 1.2 h) than after the tablet formulation (mean 4.2±SD 1.7 h).
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  • 11
    ISSN: 1432-1041
    Keywords: ergotamine ; migraine ; bioavailability ; radioimmunoassay ; plasma level ; CSF level ; continuous dosing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma ergotamine concentrations were determined by radioimmunoassay in 10 healthy subjects after a 2 mg oral dose of ergotamine, administered at 24 h intervals on three consecutive days. After the first dose the mean peak plasma level of 0.35±0.05 (SEM) ng/ml was found 1–2 h after administration. In the samples obtained 2 h after the second and third doses, plasma ergotamine levels did not exceed the first peak value. On the other hand, after the third and last dose the plasma ergotamine began to rise slowly, reaching maximum of 0.70± 0.10 ng/ml on the 6th day after administration. This supports the concept of accumulation of the drug or of immunoreactive metabolites. CSF ergotamine was determined in 4 patients, who underwent lumbar puncture for other diagnostic purposes, 1 to 2 h after the 2 mg oral dose. A concentration of 0.40± 0.03 ng/ml was observed. In seven out of 18 migraine patients who were taking ergotamine preparations daily (mean 11.7 mg/week), ergotamine could not be detected in plasma 1 h after administration of the dose. In the remaining migraine patients, the pattern of plasma ergotamine after both the daily and the test doses was similar to that of the 10 healthy subjects. The results in volunteers and migraine patients suggest notable variation in bioavailability of the drug. It seems that in most subjects there is accumulation or tissue redistribution of ergotamine or its immunoreactive metabolites, although in a significant number of migraine patients who use the drug daily, ergotamine does not appear to be biologically available.
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  • 12
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    European journal of clinical pharmacology 16 (1979), S. 405-410 
    ISSN: 1432-1041
    Keywords: diclofenac ; plasma levels ; intravenous bolus administration ; oral administration ; enteric coating ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of diclofenac were examined following single rapid intravenous injection and also following single oral doses to healthy female volunteers. After intravenous injection plasma levels of diclofenac fell rapidly and were below the limits of detection at 5.5 h postdosing. Individual drug profiles were described by a triexponential function and mean half-lives of the three exponential phases were 0.05, 0.26 and 1.1 h. After oral doses of enteric-coated tablets, the lag time between dosing and the appearance of drug in plasma varied between 1.0 and 4.5 h. However once drug absorption had commenced similar plasma drug profiles were obtained in different individuals. Peak plasma diclofenac levels ranged from 1.4 to 3.0 µg · ml−1. The mean terminal drug half-life in plasma was 1.8 h after oral doses. This value was not significantly greater than the value of 1.1 h following intravenous doses. Fifty percent of orally dosed diclofenac did not reach the systemic circulation due, predominantly, to first-pass metabolism.
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  • 13
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    Cell & tissue research 200 (1979), S. 223-227 
    ISSN: 1432-0878
    Keywords: Hypothalamus ; Lacertilian reptiles ; Vasotocin neurons ; Mesotocin neurons ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The hypothalamic magnocellular neurosecretory system of lizards was studied with the unlabeled antibody peroxidase-antiperoxidase complex (PAP) technique at the light microscopic level. It was shown that vasotocin and mesotocin are synthesized in separate neurons. The vasotocinergic as well as the mesotocinergic perikarya are of different sizes. Both cell types occur in close juxtaposition, but without a distinct pattern of distribution. The external zone of the lacertilian median eminence contains numerous immunoreactive vasotocinergic fibers and only few immunoreactive mesotocinergic fibers. The general organization of the hypothalamic magnocellular neurosecretory system of lizards, as revealed by immunocytochemistry, is essentially similar to that revealed with unspecific staining methods.
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  • 14
    ISSN: 1432-0878
    Keywords: Immunocytochemistry ; Ecdysteroids ; Prothoracic gland ; Insect hormones ; Galleria mellonella
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Fixation of prothoracic glands of Galleria mellonella with a solution containing saponin permits immunocytochemical staining of the entire gland. By this means ecdysteroids were demonstrated electron microscopically to be present in the hyaloplasm and microtubules.
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  • 15
    ISSN: 1432-0878
    Keywords: Enkephalin neurons ; Vasotocin neurons ; Isotocin neurons ; Immunocytochemistry ; Goldfish (Carassius)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Our immunocytochemical investigation of the magnocellular neuroendocrine system in the goldfish hypothalamus reveals enkephalin (ENK)-containing neurons interspersed among the vasotocin (VT)- and isotocin (IT)-containing neurons of the preoptic nucleus. The perikarya of the ENK, VT, and IT neurons do not show distinct morphological differences at the level of light microscopy and are not located preferentially within the nucleus. Separate ENK, VT and IT fibers course laterally and ventrally through the hypothalamus as they descend toward the pituitary gland. All three fiber types form terminals around blood vessels in the neurohypophysis.
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  • 16
    ISSN: 1432-0878
    Keywords: Pancreatic polypeptide (PP) ; Neurones ; Central nervous system ; Peripheral nervous system, gut ; Immunocytochemistry ; Mammals ; Birds
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Pancreatic polypeptide (PP) is a candidate hormone of unknown physiological significance. It is produced by a population of endocrine cells in the pancreas. In the present study a PP-like peptide was found to occur in the mammalian and avian central and peripheral nervous systems. Immunoreactive nerve fibres and nerve cell bodies were widely distributed in the brain. Dense accumulations of nerve fibres occurred in the following areas: nucleus accumbens, interstitial nucleus of the stria terminalis, para- and periventricular hypothalamic nuclei, and medial preoptic area. In addition, nerve fibres were regularly seen in cortical areas. Immunoreactive perikarya were observed in the following regions: cortex, nucleus accumbens, neostriatum and septum. In the gut, immunoreactive nerve fibers were distributed in the myenteric plexus, in smooth muscle, around blood vessels, and in the core of the villi. Immunoreactive perikarya occurred in the submucosal and myenteric plexus, suggesting that PP immunoreactive nerves are intrinsic to the gut. In the species examined, the neuronal PP-like peptide could be demonstrated with an antiserum raised against avian PP, but not with those raised against bovine or human PP. Thus, neuronal PP is distinct from the PP that occurs in pancreatic endocrine cells.
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  • 17
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    Cell & tissue research 200 (1979), S. 29-33 
    ISSN: 1432-0878
    Keywords: Magnocellular neurosecretory system ; Activation ; Rat ; Vasopressinergic neurons ; Oxytocinergic neurons ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The activated hypothalamic magnocellular neurosecretory system of the rat was studied in tissue sections, double stained with the unlabeled antibody peroxidase-antiperoxidase complex (PAP) technique. The results indicate that in animals with an activated hypothalamic magnocellular neuroendocrine system, as well as in normal animals, vasopressin and oxytocin are exclusively synthesized in separate vasopressinergic and oxytocinergic neurons.
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  • 18
    ISSN: 1432-0878
    Keywords: Somatostatin ; Somatostatin cells ; Rat stomach ; Paracrine action ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Somatostatin cells in the stomach of the rat have a characteristic shape and distribution. In the antral mucosa they occur together with gastrin cells and enterochromaffin cells at the base of the glands. In the oxyntic mucosa they are scattered along the entire glands with some predominance in the zone of parietal cells. Throughout the gastric mucosa the somatostatin cells possess long and slender processes that emerge from the base of the cell and end in clublike swellings. Such processes appear to contact a certain proportion of neighbouring gastrin cells in the antral mucosa and parietal cells in the oxyntic mucosa. Exogenous somatostatin given by intravenous infusion to conscious rats counteracted the release of gastrin stimulated by feeding, elevated antral pH or vagal excitation. Gastrin causes parietal cells to secrete HCl and endocrine cells in the oxyntic mucosa to mobilise and synthesise histamine. Somatostatin is known to block the response of the parietal cells to gastrin. In contrast, somatostatin did not block the response of the histamine-storing endocrine cells to gastrin, perhaps because these endocrine cells lack receptors to somatostatin. Conceivably, somatostatin in the gastric mucosa has a paracrine mode of action. The observations of the present study suggest that somatostatin may affect some, but not all of the various cell types in the stomach. Under physiological conditions this selectivity may be achieved in the following ways: 1) Communication may be based on direct cell-to-cell contact. 2) Only certain cell types are supplied with somatostatin receptors.
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  • 19
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    Cell & tissue research 201 (1979), S. 315-325 
    ISSN: 1432-0878
    Keywords: Immunocytochemistry ; Post-natal development ; Neurohypophysial peptides ; Magnocellular and parvocellular neurons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Immunocytochemical localization of vasopressin (VP), oxytocin (OXY) and neurophysins I and II (NI and NII) in the hypothalamus of growing rats revealed several new features. Hormones and neurophysins were present in magnocellular neurons of newborn rats: VP and NII in a first neuronal population, OXY and NI in a second neuronal population. For the first three days after birth, the ratio of detected VP to detected NII increased whereas the ratio of detected OXY to detected NI appeared constant. It was obvious that maturation of the OXY/NI magnocellular system occurred later than maturation of the VP/NII magnocellular system. During the first three weeks of development, VP/NII fibres in the median eminence were separated into two distinct groups: the hypothalamo-neurohypophysial tract in the internal part of the median eminence, and pericapillary endings heavily loaded with VP and NII in the external part of median eminence. OXY/NI fibres did not show this particular distribution. Therefore, during this post-natal period, loading of infundibular VP endings was related to the increase of ACTH synthesis demonstrated by various authors. Therefore, we suppose that simultaneous participation of VP and corticotropin-releasing hormone does not only appear during experimental and chronic stimulation of ACTH synthesis (after adrenalectomy, for example) but that it also exists during physiological stimulation of corticotropic function. At birth, parvocellular suprachiasmatic neurons were devoid of VP and NIL A slight immunological reactivity appeared in 6-to 10-day-old rats and it became equivalent to the immunological staining in the adult rat during the third post-natal week. Thus, the appearance of suprachiasmatic VP preceded the differentiation of the rhythmic activity of the pituitary adrenal axis. These chronological relationships suggest the involvement of the suprachiasmatic VP-related-peptide in the circadian periodicity of the corticotropic function.
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  • 20
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    Cell & tissue research 201 (1979), S. 349-359 
    ISSN: 1432-0878
    Keywords: Hypothalamus ; Rat ; Somatostatin-containing neurons ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The rat hypothalamus was studied at the light microscopic level with the use of single and double immunocytochemical staining methods. It was shown that the rat supraoptic and paraventricular hypothalamic nuclei, and their accessory neurosecretory nuclei, do not contain magnocellular somatostatin neurons. The distribution of the hypothalamic parvocellular somatostatin cells is described. The parvocellular component of the rat hypothalamic paraventricular nucleus is, at least partly, composed of somatostatin cells: they form a fairly well circumscribed periventricular cell mass. The rat suprachiasmatic nuclei contain separate somatostatin neurons and vasopressin neurons. Scattered somatostatin cells are present in the entire arcuate nucleus. In addition to the periventricular somatostatin cells located in the preopticanterior hypothalamic area and in the arcuate nucleus, the rat hypothalamus also contains numerous scattered somatostatin cells located distant from the third ventricle.
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  • 21
    ISSN: 1432-0878
    Keywords: Immunocytochemistry ; Vasopressin ; Oxytocin ; Somatostatin ; Luteining hormone releasing hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The hypothalamic hormones arginine-vasopressin (AVP), oxytocin (OXT), somatostatin (SOM), and luteinizing hormone-releasing hormone (LHRH) were localized in the rat neurohypophysis by the use of semithin serial sections and the unlabeled antibody enzyme method. Clusters of AVP fibres are present within the central region of the neural lobe, clusters of OXT fibres mainly in the peripheral part. The AVP fibres enter bilaterally into the neural lobe. The results call into question previous reports on the presence of AVP on receptors in the pars intermedia cells, since incubation with anti-AVP resulted in similar staining in the pars intermedia of the Wistar and homozygous Brattleboro rat, a mutant strain deficient in AVP. The same intermediate lobe cells are stained after incubation of serial sections with anti-AVP and anti-α-melanocyte-stimulating hormone (α-MSH). This staining of anti-AVP could be removed by solid phase absorption to α-MSH and is thus most probably due to cross reaction with α-MSH. SOM fibres appear to be present in the peripheral parts of the proximal neurohypophysial stalk and mainly lateral in its more distal parts. In the neural lobe they rapidly decrease in number, although some fibres continue into the distal part of the neural lobe, running bilaterally and situated adjacent to the pars intermedia. The SOM staining within magnocellular elements, which has been reported in the literature, can most probably be explained by cross reaction of anti-SOM with neurophysins. LHRH fibres are very scarce in the neurohypophysial stalk and absent in the neural lobe.
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  • 22
    ISSN: 1432-0878
    Keywords: Immunocytochemistry ; ACTH ; Lymnaea stagnalis ; Neurohormone ; Neurotransmitter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Two giant neurons (diameter 130 μm) were identified immunocytochemically by means of the unlabeled antibody enzyme technique with anti ACTH 1–39 and 1–24 in the pond snail Lymnaea stagnalis. The cells are located in the visceral and the right parietal ganglion, respectively. They contain moderately electron dense elementary granules (diameter 150–160 nm). By means of the intracellular horseradish peroxidase injection technique it was shown that the cells send fibres into the neuropiles of various ganglia and into nerves. Synapses occur on the fine fibre branches in the neuropile. Synapse-like structures were found on the cell bodies and on the major fibres. The giant neurons are electrotonically coupled. With toluidine blue staining for small peptides it was demonstrated that in the central nervous system of the pond snail numerous peptidergic neurons occur in addition to those identified with the classical staining methods for neurosecretion.
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  • 23
    ISSN: 1432-0878
    Keywords: Isotocinergic neurons ; Immunocytochemistry ; Hypothalamus ; Intracellular recording ; Goldfish (Carassius)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Isotocinergic (IT) neurons show physiological and morphological characteristics that are similar to those of other preoptic neuroendocrine cells in the goldfish. Preoptic IT cells show resting membrane potentials of 20–55 mV, action potentials of up to 100mV, and physiological evidence of axonal branching. Dye-marked IT cells measure 14–56 μm, their dendrites projecting to the ependyma and into the hypothalamic neuropil, their multiple beaded axons projecting to the pituitary. Indirect immunofluorescence identifies these dyemarked cells as IT. By combining electrophysiological, dye-marking and immunocytochemical techniques we can now, for the first time, study single, antidromically-identified peptidergic neurons of a specific type in vertebrate and invertebrate species.
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  • 24
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    Cell & tissue research 202 (1979), S. 251-261 
    ISSN: 1432-0878
    Keywords: Somatostatin ; Growth hormone ; Mouse Fetus ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The objective of the present study was to determine, by means of immunocytochemistry, the age in fetal development at which GH is first detectable in the pituitary gland and somatostatin in the median eminence, and to correlate temporally the development of these two hormones throughout the remainder of pregnancy. Mice were studied at 15–19 days of gestation with the peroxidase-antiperoxidase (PAP) technique of Sternberger. Somatotropes in the pars distalis were initially detected at 16 days of gestation and by 17 days they were a prominent component of the parenchymal cell population of the hypophysis. These cells were ovoid and distributed uniformly throughout the pars distalis; many were located adjacent to sinusoidal capillaries. Their number and staining intensity increased by 19 days. Somatostatin was not consistently observed in the median eminence until 19 days of gestation. Reaction product indicative of the presence of somatostatin in presumptive nerve endings was located on the ventral surface of the median eminence and in the external lamina of the infundibulum in proximity to the superficial portal capillaries. Results of the present investigation support the concept that the potential for neuroendocrine control of GH secretion exists in the mouse by the end of fetal development. Several hypotheses concerning the temporal relationship between the appearance of somatostatin in the hypothalamus and of GH in the anterior pituitary gland are discussed.
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  • 25
    ISSN: 1573-8744
    Keywords: quinidine ; pharmacokinetic parameters ; assay methods ; assay specificity ; area under the plasma concentration-time curve ; bioavailability ; clearance ; therapeutic window
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Previously published estimates of pharmacokinetic characteristics of quinidine can be shown to be dependent on whether the investigators have used analytical methods which are specific for quinidine. Areas under the plasma concentration-time curve and peak plasma concentrations after administration of the drug were higher and clearance values consequently lower in studies utilizing nonspecific assays unable to distinguish quinidine from its metabolites. The error introduced is larger after oral administration as a result of marked first-pass metabolism of quinidine. The absolute oral bioavailabilities from pharmaceutical preparations might therefore be estimated higher in studies with assays including metabolites in the determination. Although the pharmacodynamic response to quinidine is related to the plasma concentration, the therapeutic window of drug concentrations has been defined only using nonspecific assays. In light of the availability of newly developed specific assays, redefinition of the range of therapeutic plasma concentrations is opportune.
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  • 26
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    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 429-451 
    ISSN: 1573-8744
    Keywords: ampicillin ; bacampicillin ; pivampicillin ; prodrug ; bioavailability ; zero-order absorption ; two-compartment model ; renal clearance
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Five healthy fasting male subjects were each given single doses of intravenous ampicillin (471 mg), oral ampicillin tablets (495 mg), oral bacampicillin hydrochloride tablets (562 mg ampicillin equivalent), and oral pivampicillin hydrochloride capsules (491 mg ampicillin equivalent) in a crossover experiment. The resulting concentrations of ampicillin were determined in plasma and urine. The pharmacokinetic analysis was made according to a two-compartment open model. The total distribution volume of unbound ampicillin during the disposition phase was 0.247 ± 0.045 (sd) liter/kg, which is only slightly more than the extracellular fluid, suggesting that tissue binding and intracellular distribution of ampicillin are limited. The bioavailability of the esters bacampicillin (86 ± 11%) and pivampicillin (92± 18%) was significantly greater than that of ampicillin (62 ± 17%); however, the difference between the esters was not statistically significant. The absorption for all drugs given orally proceeded at a constant rate, suggesting zero-order release rates from the products. The absorption rate was highest for bacampicillin (0.89 ± 0.39% of dose absorbed per minute), followed by pivampicillin (0.64 ± 0.19) and ampicillin (0.58 ± 0.16). Bacampicillin also had the shortest lag time for the start of absorption (7.0 ± 0.9 min) under the present conditions. Thus, in comparison with ampicillin, the esters have a higher bioavailability, which, in fact, is close to the theoretically highest possible value by clearance concepts. The higher bioavailability in connection with higher absorption rates may be clinically important in ampicillin treatment by the oral route.
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  • 27
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    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 1-27 
    ISSN: 1573-8744
    Keywords: furosemide ; renal failure ; congestive heart failure ; bioavailability ; diuretic effects
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of furosemide and the attempt to correlate biological fluid measurements with diuretic response have been the subject of a large number of studies since the original reports of HajdÚ, Rupp, and coworkers in the mid-1960s. This article attempts to critically review these studies under seven different sections: furosemide pharmacokinetics in normal volunteers, furosemide pharmacokinetics in patients with decreased renal function, furosemide pharmacokinetics in patients with congestive heart failure, furosemide metabolism and assay methods, furosemide bioavailability, dose-response relationships, and the role of inhibitors and mediators on furosemide effects. The literature is reviewed through August 1978.
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  • 28
    ISSN: 1573-8744
    Keywords: bioavailability ; confidence intervals ; hypothesis testing ; imipramine ; internal standard ; mass spectrometry ; power ; relative bioavailability
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    Topics: Chemistry and Pharmacology
    Notes: Abstract A new methodology for comparative bioavailability testing is described in which each drug formulation is compared with a stable isotope-labeled variant of the drug that is consumed orally in solution at the same time the tested formulation is ingested. The methodology is used to determine the comparative bioavailabilities of two commercially available brands of imipramine hydrochloride. The power of the new methodology to detect differences between drug formulations, when, in fact, such differences exist, is shown to be superior to that of conventional bioavailability tests.
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  • 29
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    Cell & tissue research 197 (1979), S. 69-77 
    ISSN: 1432-0878
    Keywords: Calcium-binding protein ; Duodenum ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The cellular localization of the vitamin D-dependent calcium-binding protein (CaBP) in the duodenum of rat was studied using indirect immunofluorescence and immunoperoxidase staining methods. Specific positive reaction product, indicative of the presence of CaBP, was exclusively located within the villous part of the duodenal mucosa. Moreover, CaBP was detected mainly within the supranuclear region of the cytoplasm of absorptive cells and also at the level of their basal laminae. CaBP was not demonstrable either in the nuclei or associated with the brush border membrane of absorptive cells. Also, CaBP was neither detectable in goblet cells nor in sub-epithelial layers. When the specific anti-CaBP antiserum was replaced by nonimmune rabbit serum or when it was preabsorbed on a CaBP-Sepharose conjugate, no positive immunostaining was seen. Together with recent biochemical data our observations agree well with the view that CaBP may act as an intracellular “buffer” by protecting the cell against too high Ca2+ concentrations.
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  • 30
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    Cell & tissue research 197 (1979), S. 295-312 
    ISSN: 1432-0878
    Keywords: Thyroid gland ; C cells ; Ultimobranchial body ; Immunocytochemistry ; Morphometry
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    Topics: Biology , Medicine
    Notes: Summary Thyroid tissue of 300 routine autopsies was processed in a standardized manner. So-called solid cell nests (SCN) were found in 21 patients (7 %). These cases were investigated carefully by serial step sectioning. In order to explore the correlation of SCN to the C-cell system, the sections were stained by silver impregnation and the immunoperoxidase method. Morphometric analyses revealed a significant increase in the density of C cells in the proximity of the SCN. With progressive distance from the SCN, the C-cell density decreased and reached normal values. In 30 % of the cases argyrophilic and calcitonin-positive cells were found lying within the SCN. Occasionally, mixed follicles could be discerned: These were lined on the one side by a multilayered squamous epithelium, on the other side by normal monolayered cubic follicular epithelium, and contained a peculiar granular material. In one case, SCN were associated with intrathyroid portions of the parathyroids and adult adipose tissue, in a second case with adipose tissue only. Most probably SCN are vestiges of the ultimobranchial body and should be interpreted as such, despite the fact that other authors have expressed different views. The lack of disturbances in the calcium metabolism of the patients and the absence of medullary carcinoma in their family histories led us to interpret locally confined C-cell hyperplasia not as reactive nor premalignant, but rather as normal.
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    Cell & tissue research 203 (1979), S. 201-207 
    ISSN: 1432-0878
    Keywords: β-Endorphin ; LH-RH neurons ; Fetal human hypothalamus ; Immunocytochemistry
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    Topics: Biology , Medicine
    Notes: Summary A peptide immunochemically related to β-endorphin was detected in some LH-RH neurons of the fetal human hypothalamus by comparison of adjacent sections stained for β-endorphin and for LH-RH. In the same section, by successive staining and after antibody elution, both peptides were again revealed in the same neuron. The significance of the presence of the β-endorphin-like material in LH-RH neurons is discussed.
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  • 32
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    Cell & tissue research 203 (1979), S. 415-426 
    ISSN: 1432-0878
    Keywords: Colon ; Human fetus ; Endocrine cells (distribution) ; Immunocytochemistry ; Ontogeny
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    Topics: Biology , Medicine
    Notes: Summary In 9 fetuses, 9 to 24 weeks-old, the occurrence and relative distribution of argentaffin cells, as well as of cells immunoreactive to somatostatin (SRIF), glucagon-like polypeptide (GLI), pancreatic polypeptide (PP) and substance P (SP) were studied in five segments of the colon (appendix, cecum, ascending colon, descending colon, and rectosigmoid). For each colonic segment, data concerned with the occurrence of endocrine cells were expressed either as mean absolute numbers of specific cells per entire mucosal section, or as cell densities per mm3 of mucosa after calculation of the mucosal volume of the sections. Argentaffin, GLI, SRIF and PP immunoreactive cells are all present in relatively large numbers, scattered along the entire length of the colonic mucosa as early as the 9th–10th week of gestation, whereas substance P-containing cells occur sporadically and first appear during the 14th–17th week. Until the 20th week, with progressing embryonic development, an increase was determined in absolute numbers per section of all types of endocrine cells in all segments of the colon. This observation is clearly related to the general growth of the colonic mucosa, since cell densities per mm3 of mucosa do not greatly change or even decrease during gestation. However, it is possible that densities of argentaffin, GLI and BPP cells increase in the appendix around the 14th–17th week of gestation. Between the 20th and 24th week, absolute numbers of cells per section remain stable or slightly increase, while cell densities tend rather to decrease in all segments. These data demonstrate that some endocrine cells are present very early in the human fetal colon, but their functional significance remains to be elucidated.
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  • 33
    ISSN: 1432-0878
    Keywords: Median eminence ; Hypophysis ; Rana temporaria ; Vasotocinergic fibres ; Mesotocinergic fibres ; Immunocytochemistry ; Electron microscopy
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    Topics: Biology , Medicine
    Notes: Summary With the use of the unlabelled antibody peroxidase-antiperoxidase complex (PAP) technique at the electron microscopic level, it was shown that both the internal and the external regions of the median eminence of the frog contain separate vasotocinergic and mesotocinergic nerve fibres. This observation confirms the results of previous immunocytochemical studies at the light microscopic level. The mean size of the neurohypophysial hormone-containing granules in the external region of the median eminence is significantly smaller than that of the neurohypophysial hormone-containing granules in the internal region of the median eminence. No significant difference could be found between the mean granule size of the vasotocinergic and mesotocinergic fibres of either the internal or the external region of the frog median eminence.
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  • 34
    ISSN: 1432-0878
    Keywords: Cyproterone acetate ; 17β-Oestradiol ; 5α-Androstane-3α,17β-diol ; Prostate gland ; Pituitary gland ; Immunocytochemistry ; Dog (beagle)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The antiandrogen, cyproterone acetate (CPA), prevents development of prostatic hyperplasia, induced in castrated dogs by a 6 month-treatment with 5α-androstane-3α,l 7β-diol (A)alone or in combination with 17β-oestradiol (E 2). The immunoperoxidase technique was used to study functional cell types in the pars distalis of the pituitary gland and to detect growth hormone (GH) and prolactin (PRL) target sites in the prostate gland. Homologous radioimmunoassays for estimation of serum canine GH and PRL concentrations were also performed. Treatment with the combinations A + E 2 and A + E 2 + CPA resulted in morphological indications of stimulated GH and PRL cells and depressed gonadotrophs. This correlates well with an increase in PRL-dependent staining in glandular epithelium and fibromuscular tissue of the prostate gland. However, basal serum PRL and GH levels were not significantly affected. Treatment with A and A + E2 stimulated, while additional treatment with CPA clearly suppressed adrenocorticotrophin/melanotrophin (ACTH/MSH) cells. These findings indicate that an endocrine imbalance in hypothalamic-pituitary-adrenal function may be involved in induction and prevention of prostatic hyperplasia in the dog.
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  • 35
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    Cell & tissue research 196 (1979), S. 117-122 
    ISSN: 1432-0878
    Keywords: Vasopressin neurons ; Oxytocin neurons ; Immunocytochemistry ; Magnocellular neuroendocrine system ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Our immunocytochemical investigation of the magnocellular neuroendocrine cells in the cat hypothalamus reveals a mixture of vasopressin (VP)- and oxytocin (OT)-containing neurons in the supraoptic (NSO), the paraventricular (NPV) and in five accessory nuclei (NAC). We describe the lateral hypothalamic nucleus (NLH), a new accessory nucleus, lying at the junction of the internal capsule and pallidum, and possibly involved in drinking behavior. Previously characterized incompletely in mammals, the four other accessory nuclei consist of the circularis (NC), anterior fornical (NAF), posterior fornical (NPF) and retrochiasmatic (NRC). The two peptidergic cell types, VP and OT, are equally mixed in the NPV and the NAC, but in the NSO VP neurons predominate. The perikarya of these VP and OT neurons do not show distinct morphological differences at the level of light microscopy. The organization of magnocellular neurosecretory neurons in the cat hypothalamus closely resembles that described in other mammals with the exception of the unique presence of the lateral hypothalamic accessory nucleus.
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  • 36
    ISSN: 1432-0878
    Keywords: Supraoptic and paraventricular nuclei (Man) ; Vasopressin-neurophysin neurons ; Oxytocin-neurophysin neurons ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary With the use of immunocytochemistry, it was shown that both the supraoptic and paraventricular hypothalamic nuclei in humans contain at least two different neurophysins. These two human neurophysins are immunologically related to bovine neurophysin I and neurophysin II, respectively. One human neurophysin is associated with vasopressin, the other with oxytocin. Human vasopressin-neurophysin and oxytocin-neurophysin are located separately in two different types of neurons, which correspond respectively to the vasopressinergic and oxytocinergic neurons of both the supraoptic and paraventricular nuclei. The neurophysin of the human vasopressinergic suprachiasmatic neurons appears to be closely related to or identical with neurophysin of the vasopressinergic neurons of the human magnocellular hypothalamic nuclei.
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  • 37
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    Cell & tissue research 196 (1979), S. 525-530 
    ISSN: 1432-0878
    Keywords: ACTH ; Human hypothalamus ; Immunocytochemistry
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    Topics: Biology , Medicine
    Notes: Summary Using an antiserum to porcine ACTH and the unlabeled antibody peroxidase-antiperoxidase technique, we have found that ACTH is present in neuronal cell bodies located exclusively in the arcuate nucleus of the human hypothalamus. ACTH-containing fibers are distributed extensively throughout the hypothalamus with the greatest density in the periventricular nucleus. No concentration of ACTH fibers could be observed in the neurovascular zone of the pituitary stalk.
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  • 38
    ISSN: 1432-0878
    Keywords: Immunocytochemistry ; Thyroid stimulating hormone (TSH) ; Pituitary gland ; Duck
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    Topics: Biology , Medicine
    Notes: Summary Cells binding anti-bovine TSH β serum were found exclusively in the rostral lobe of the adenohypophysis of the drake using the peroxidase-antiperoxidase complex unlabelled antibody method. The specificity of the binding of the anti-serum to TSH cells was established by relating the morphology and relative abundance of immunochemically stained cells to the TSH content of the adenohypophysis after experimentally altering the activity of the pituitary-thyroid axis. The TSH activity of the adenohypophysis was assessed indirectly, by the weight of the thyroid glands, and directly, by bioassay. As determined by bioassay, the TSH content of the rostral lobe of the adenohypohysis was much greater than that of the caudal lobe. Compared with control drakes, immunochemically stained cells in birds fed a goitrogen, methimazole, seemed to be enlarged and were closer together, while the stained cells in drakes injected with thyroxine were shrunken and less intensely stained. The TSH content of the adenohypophysis was increased in drakes fed methimazole. Castration did not alter the TSH content of the adenohypophysis or change the morphology of immunochemically stained cells. These observations suggest that in the drake: 1) anti-bovine TSH β serum binds specifically to TSH cells; 2) the TSH cells occur in the rostral and not in the caudal lobe of the adenohypophysis; and 3) the activity of TSH cells is not inhibited by the feedback effects of gonadal steroids.
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  • 39
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    Cell & tissue research 196 (1979), S. 307-319 
    ISSN: 1432-0878
    Keywords: Pituitary-Intermediate lobe ; Immunocytochemistry ; α, MSH, ACTH, Endorphin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The question is examined whether α-melanocyte stimulating hormone (α-MSH), adrenocorticotropic hormone (ACTH), met-enkephalin and β-endorphin are detectable by enzyme immunocytochemistry in the cells of the intermediate lobe (PI) of the rat pituitary. By applying antibodies against αMSH, ACTH and β-endorphin on light microscopic sections, intense immunostaining was found in all PI-cells. At the ultrastructural level, after treatment of consecutive serial sections with these three antibodies the immunoreactivity was localized in the same secretory granules. No specific metenkephalin immunoreactivity could be detected in the cells of the intermediate lobe.
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  • 40
    ISSN: 1432-2048
    Keywords: Avena ; Immunocytochemistry ; Phytochrome
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    Topics: Biology
    Notes: Abstract Phytochrome of oat (Avena sativa L., cv. Garry) coleoptile cells in the red-light-absorbing form, Pr, is diffusely distributed while after conversion to the far-red-light-absorbing form, Pfr, it is observed only in very small areas within the cell. Comparison of phytochrome photoversibility measurements to the distribution of the pigment within the cell indicates that the spectral assay is not influenced by the observed compartmentalization of the chromoprotein. However, the observed compartmentalization of phytochrome is correlated with a loss in spectrophotometrically detectable Pr.
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  • 41
    ISSN: 1432-1041
    Keywords: p-Chlorophenoxyisobutyric acid ; clofibrate ; steady-state plasma concentrations ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations and bioavailability of clofibrinic acid have been estimated under conditions approaching the steady-state during a ten-day period of administration as clofibrate or as a calcium clofibrinate-carbonate combination (1:1 w/w) at a dosage interval of 12 h. Formulation — related differences in bioavailability were not significant, and the 95% confidence limits of these differences were within −2% to +8% of the mean for the reference formulation of clofibrate. The mean steadystate plasma concentrations of clofibrinic acid measured on the tenth day of dosing were 116 µg/ml±22 S.D. and 119 µg/ml±23 S.D. after administration of 885 mg as clofibrate and the calcium clofibrinate-carbonate combination respectively. The peaks of mean plasma concentrations were 70 µg/ml±15 S.D., 119 µg/ml±32 S.D. and 131 µg/ml±26 S.D. on the first, fifth and tenth day of dosing with clofibrate, and 62 µg/ml±13 S.D., 127 µg/ml±S.D. and 143 µg/ml±25 S.D. on the corresponding days of dosing with the calcium clofibrinate-carbonate combination. After the last dose on the tenth day of dosing, the mean apparent half-lives of elimination of clofibrinic acid from plasma were 24.2 h±4.4 S.D. and 25.5 h±3.2 S.D. after administration of clofibrate and the calcium clofibrinate-carbonate combination respectively.
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  • 42
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    European journal of clinical pharmacology 13 (1978), S. 125-128 
    ISSN: 1432-1041
    Keywords: bioavailability ; diuretics ; gastrointestinal absorption ; hydrochlorothiazide ; thiazides ; food effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Hydrochlorothiazide (hct) 75 mg was administered orally to eight healthy volunteers without (Study I) or together with a standardized meal (Study II), and plasma and urine concentrations of hct were analyzed by GLC. The plasma levels of hct were higher initially when the tablets were taken on an empty stomach, but after 5 h they were higher in Study II. There was no difference between the two studies in the area under plasma concentration time curves. The urinary recovery of hct totalled 55.6±4.9 mg when the drug was given with food and 47.4±6.0 when it was taken on an empty stomach. The difference is significant (p〈0.01). As the urinary recovery represents the uptake of hct, it appears that the gastrointestinal absorption of hct is enhanced when the drug is given with food.
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  • 43
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    European journal of clinical pharmacology 14 (1978), S. 253-259 
    ISSN: 1432-1041
    Keywords: Pseudoephedrine ; side effects ; bioavailability ; multiple oral dosing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Dose tolerance and pharmacokinetic studies of pseudoephedrine sustained action capsules were performed in thirty-three adult male subjects who received either 120 mg or 150 mg capsules every twelve hours for seven consecutive days in a double-blind parallel design study. Although only one subject in the 150 mg group was discontinued prematurely from this study, a large number of side effects typical of CNS stimulation were seen. A placebo effect might account for a portion of these complaints, however symtoms evaluated as being due to drug were significantly more severe and persistent in the 150 mg group. Pulse rates showed a persistent and significant increase while systolic and diastolic blood pressure fell from the baseline values in both groups. A pharmacokinetic analysis of the pseudoephedrine plasma concentration-time data provided estimates of half-life and the volume of distribution/availability ratio. The values obtained were in good agreement with values reported by others. Half-life was not influenced by urine pH probably as a result of the narrow range of urine pHs observed in the subjects. Calculations of relative bioavailability suggest that the 120 mg capsule formulation has a 30% greater bioavailability compared to the 150 mg capsule.
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  • 44
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    European journal of clinical pharmacology 13 (1978), S. 267-274 
    ISSN: 1432-1041
    Keywords: Chlordiazepoxide ; benzodiazepines ; pharmacokinetics ; bioavailability ; intramuscular injection ; alcohol withdrawal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of oral and intramuscular (i. m.) chlordiazepoxide hydrochloride (CDX · HCl) was compared in two pharmacokinetic studies. In Study One, single 50-mg doses of CDX · HCl were administered orally and by i. m. injection to 14 healthy volunteers using a crossover design. Whole-blood concentrations of chlordiazepoxide (CDX) and its first active metabolite, desmethylchlordiazepoxide (DMCDX), were determined in multiple samples drawn after the dose. Mean pharmacokinetic variables for CDX following oral and i. m. administration, respectively, were: highest measured blood concentration, 1.65 vs 0.87 µg/ml (p〈0.001); time of highest concentration, 2.3 vs 7.6 h after dosing (p〈0.001); apparent absorption half-life, 0.71 vs 3.39 h (p〈0.001). Biphasic absorption after i. m. injection, consistent with precipitation at the injection site, was observed in 9 of 14 subjects. Based upon comparison with previous intravenous data, the completeness of absorption was 100% for oral vs 86% for i. m. CDX · HCl (p〈0.1). In Study Two, 28 male chronic alcoholics with clinical manifestations of the acute alcohol withdrawal syndrome were randomly assigned to one of four treatment conditions: 50 or 100 mg doses of CDX · HCl, by mouth or by i. m. injection. Concentrations of CDX and DMCDX, determined in plasma samples drawn every 20 min for 5 h following the dose, were significantly higher after oral administration of a given dose than at corresponding points in time after i.m. injection after the same dose. Thus absorption of oral CDX is reasonably rapid and complete, whereas the absorption rate of i. m. CDX is slow.
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  • 45
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    European journal of clinical pharmacology 13 (1978), S. 35-39 
    ISSN: 1432-1041
    Keywords: Norethindrone ; bioavailability ; man ; competitive protein binding ; sex differences ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A competitive protein binding assay for norethindrone was developed to measure plasma levels in human subjects. The plasma levels were considerably higher in women than in men, especially at low dose levels. The plasma levels were directly related to the dose in men; but greater variations in the plasma levels were observed in women. The plasma half-life was about 5 h in both sexes with single oral doses of 5 to 20 mg. A comparative bioavailability study with norethindrone from 2 different manufacturers, formulated in the same manner, showed no significant differences in absorption characteristics and provided sufficient data for pharmacokinetic analysis.
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  • 46
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    European journal of clinical pharmacology 14 (1978), S. 261-265 
    ISSN: 1432-1041
    Keywords: Procainamide ; slow release formulations ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Procainamide was given to 20 patients with normal renal function as an i.v. bolus of 500 mg followed by 1.0 or 1.5 g eight-hourly by mouth in the form of a slow release preparation (Durules). 97.6±27.1 (SD)% of the oral procainamide was absorbed, the absorption half life being 1.54 h. The elimination half life following the oral formulation was 6.0±0.8 h, compared to a mean of 3.4±0.4 h following i.v. administration. Elimination half life following i.v. administration was slightly related to acetylator status, being 2.75±0.9 h in fast acetylators, and 4.4±2.4 h in slow acetylators. This dependence on acetylator status was not seen in half life following oral administration. Total body clearance, steady state plasma procainamide and N-acetylprocainamide were not significantly dependent on acetylator status, although a few patients who are slow acetylators had unexpectedly low clearance and high steady state procainamide concentrations when given the higher dose.
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    European journal of clinical pharmacology 14 (1978), S. 357-360 
    ISSN: 1432-1041
    Keywords: Lanoxin tablets ; Lanoxicaps ; sorbitol ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary (1) The mean cumulative urinary digoxin excretion over 8 days was compared in 8 healthy volunteers after single doses of digoxin administered as 3 Lanoxin tablets of 0.25 mg, 3 digoxin tablets of 0.2 mg, 12 Lanoxicaps without sorbitol of 0.05 mg, 6 Lanoxicaps without sorbitol of 0.1 mg digoxin, 3 Lanoxicaps without sorbitol of 0.2 mg and 3 Lanoxicaps with sorbitol of 0.2 mg. (2) There was no significant difference between the 8 day cumulative urinary excretion for any of the Lanoxicaps treatments. (3) Cumulative urinary excretion after 3 digoxin tablets of 0.2 mg was significantly (P〈0.05) lower than after all other treatments. (4) Cumulative urinary excretion after 3 Lanoxin tablets of 0.25 mg was not significantly different from that after any of the Lanoxicaps treatments except 0.1 mg Lanoxicaps without sorbitol, it was significantly (P〈0.05) lower after the latter. (5) Mean urinary excretion of digoxin was 60% of ingested dose for all Lanoxicaps treatments and was significantly (P〈0.05) higher than the mean value of 50% for both tablet treatments. (6) Enhanced absorption of digoxin from Lanoxicaps was confirmed and shown to be unrelated to the sorbitol content of the capsule shell.
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  • 48
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    Cell & tissue research 186 (1978), S. 399-412 
    ISSN: 1432-0878
    Keywords: Pituitary gland ; Dog ; Pars distalis ; Thyrotropin (TSH) ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Using the immunoperoxidase technique and antisera to the specific beta (β) subunits of bovine and rat TSH1, selective immunocytochemical staining was localized in a specific cell population in the pars distalis of the dog pituitary gland. These TSH cells were found to be positive to aldehyde fuchsin, alcian blue, periodic acid-Schiff (PAS) and aniline blue. With the performic acidalcian blue (pH 0.2) -PAS-orange G procedure these cells stained blue-purple, demonstrating FSH/LH cells (blue or turquoise), ACTH/MSH cells (redpurple) and PRL cells (orange-red). The TSH cells were further differentiated from other functional cell types of the pars distalis on the basis of their typical cytological features, intraglandular distribution and by immunocytochemical double staining. In the pars distalis of adult male dogs the TSH cells were mostly shown to be smaller in size and less numerous than in bitches in the anestrous phase of the sexual cycle. Moreover, cytological alterations in the immunoreactive thyrotrophs in the pituitary of male and female dogs generally paralleled the spontaneous changes in thyroid function associated with thyroid atrophy and/or pituitary insufficiency, and thyroid hyperplasia or goiter. In conclusion, because of their specificity and high potency, the antisera to the β-subunits of bovine and rat TSH represent an effective tool for the selective immunocytochemical localization of TSH in the dog pituitary. This allows the study of the morphology and function of TSH cells under different physiological, pathological and experimental conditions.
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  • 49
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    Cell & tissue research 188 (1978), S. 99-106 
    ISSN: 1432-0878
    Keywords: LHRH-neurosecretion ; Avian hypothalamus ; Vasotocin neurosecretion ; Immunocytochemistry
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    Topics: Biology , Medicine
    Notes: Summary A fluorescent technique applying specific LHRH and vasotocin antisera was used for the immunocytochemical localization of the respective neurosecretory systems in the hypothalamus of gonadectomized, testosteronetreated and/or serotonin injected male domestic ducks. An immunoreactive (IR) LHRH-producing system, with perikarya located in the preoptic nucleus, could be traced through the ventral hypothalamus down to the external layer of the rostral and caudal ME, in close vicinity to the hypophysial portal system. An IR-vasotocin system originating in the paraventricular and supraoptic nuclei ran through the ventral hypothalamus, but terminated in (i) the external layer of the rostral ME, and (ii) in the posterior lobe of the hypophysis.
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  • 50
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    Cell & tissue research 188 (1978), S. 119-132 
    ISSN: 1432-0878
    Keywords: Neurophysin ; Paraventricular nucleus ; Supraoptic nucleus ; Sheep ; Immunocytochemistry
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    Topics: Biology , Medicine
    Notes: Summary An antiserum cross-reactive against ovine neurophysins-I-II and -III has been used in conjunction with the immunoperoxidase histochemical procedure to localize the cells of the sheep paraventricular (PVN) and supraoptic nuclei (SON). In order to describe the topographical distribution of the SON and PVN a study was made on the serial sections cut (a) transversely from rostral to caudal positions and (b) sagittally from lateral to medial positions of the hypothalamus. The cells of the SON, when examined in the transverse aspect, extended approximately 1900 μ caudally and when examined in the sagittal plane were contained within a lateral-medial distance of 4830 μ. In each case the SON cells lay adjacent to the optic chiasm. As sections were cut transversely, the cells of the PVN first appeared in a rostral position defined as 0 μ and close to the ventral lining of the third ventricle. This general ventral and ventro-lateral distribution of cells maintained up to a caudal distance of approximately 840 μ. From positions 1260–2310 μ there was a dramatic dorsal shift of the PVN cells which by this time had also extended laterally. The total rostral-caudal distance occupied by the PVN cells was 3150 μ. That the lateral-medial distance occupied by the PVN was small (1050 μ) was determined on examining the magnocellular nuclei in sagittal section.
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  • 51
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    Cell & tissue research 188 (1978), S. 259-264 
    ISSN: 1432-0878
    Keywords: Hypothalamus ; Human fetus ; Oxytocin ; Neurophysin ; Immunocytochemistry
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    Topics: Biology , Medicine
    Notes: Summary The use of antibodies against oxytocin or neurophysin enabled the detection by immunocytochemistry of oxytocin-neurophysin neurons in the hypothalamus in the human fetus. The perikarya of these neurons are located in the paraventricular and supraoptic nuclei. Immunoreactive neurons occur in the median eminence. The neurophysin immunoreactive neurons were more numerous than the oxytocin immunoreactive neurons. The specificity of the immunocytological reaction was controlled. The first oxytocin-neurophysin neurons are seen as early as the 14th week of gestation.
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  • 52
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    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 265-282 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; linear systems analysis ; in vivo dissolution rates ; absorption rates ; metabolic rates ; bioavailability ; numerical desconvolution
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The application of certain aspects of linear systems analysis to pharmacokinetic-problems is described. Topics covered include the evaluation of in vivodissolution rates, absorption rates, and metabolic rates, and the use of pharmacological data. Relevant numerical procedures are also discussed.
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  • 53
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    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 99-110 
    ISSN: 1573-8744
    Keywords: bioavailability ; tetracycline HCl capsules ; dose dependency ; brand dependency ; water ingestion ; urinary excretion
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Seven healthy male volunteers were administered, on different occasions, one, two, and three capsules of two commercially available brands (A and B) each containing 250 mg tetracycline HCl. Urinary excretion rates and cumulative amounts of drug excreted in the urine in 4 days were used to assess the bioavailability of the two brands at the different doses studied. The rate constants of absorption and elimination of tetracyline were similar at all dose levels. However, the extent of absorption (F)appears to be dependent on the brand, dose, and volume of water ingested with the drug. Fof Brand B was not significantly different than that of brand A at the 250-mg dose but was decreased by 23.3% (p〈0.01)at the 500-mg dose and by 19.7% (p 〈0.05) at the 750-mg dose. With respect to dose, Fof each brand at the 500-mg dose was not significantly different than its value at the 250-mg dose. However, Fof brand A at the 750-mg dose was reduced by 14.8% (p 〈0.05) and that of brand B by 21.1% (p 〈0.05) relative to their respective values at the single dose. Surprisingly, when the 750-mg dose of brand A was ingested with a small volume of water, Fwas increased by 18.9% (p 〈0.05) compared to the ingestion of the identical dose of the same brand under waterloading conditions.
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  • 54
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    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 547-558 
    ISSN: 1573-8744
    Keywords: statistical moments ; network theory ; pharmacokinetics ; bioavailability ; deconvolution ; plasma concentration-time curve ; urinary excretion rate-time curve ; compartment models
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Statistical moments are parameters that describe the characteristics of the time courses of plasma concentration (area, mean residence time, and variance of residence time) and of the urinary excretion rate that follow administration of a single dose of a drug. The relationship between the moments of a time-course curve and pharmacokinetic profiles of drug disposition, i.e., absorption, distribution, metabolism, and excretion, is described. The moments are related to the extent and rate of bioavailability, and it is shown that they can be effectively applied to the deconvolution operation.
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  • 55
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    Keywords: trapezoidal rule ; area under the curve ; pharmacokinetics ; clearance ; bioavailability ; integration method ; sulfisoxazole
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The linear trapezoidal rule method is commonly used for the estimation of the area under the plasma level-time curve. Error analyses are performed when the method is used in first-order absorption and first-order elimination kinetics in the one-compartment system. It is found that significant underestimations and overestimations in area during the absorption phase and postabsorption phase, respectively, can occur when the method is improperly used. During the exponential postabsorption phase the relative error is only a function of the ratio (n)of the time interval over the half-life of the two plasma data points in the interval. The error from the linear trapezoidal rule method at n=0.5 is about 1%. The error increases to 15.5% and 57.1 % when nis increased to 2 and 4, respectively. It is recommended that for most absorption studies the linear trapezoidal method be used for prepeak and plateau plasma data and the logarithmic trapezoidal method for postpeak plasma data.
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  • 56
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    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 295-303 
    ISSN: 1573-8744
    Keywords: tetracycline ; antibiotics ; Billroth-II gastrectomy ; gastrectomy ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The bioavailability of a single 250-mg oral dose of tetracycline hydroghloride was studied in seven patients following Billroth-II gastrectomy in comparison with seven control subjects matched for age and body weight. There were no significant differences between control subjects and gastrectomized patients in the apparent lag time prior to the start of absorption (23.6 vs. 22.8 min), peak serum tetracycline concentration (1.72 vs. 1.75 μg/ml), the time of attainment of peak concentrations (3.35 vs. 3.42 hr), the apparent first-order absorption half-life (1.8 vs. 1.4hr), or the apparent first-order elimination half-life (8.0 vs. 8.7hr). Completeness of tetracycline absorption, as judged by area under the 24-hr serum concentration curve, did not differ significantly between the two groups, nor did 24-hr urinary excretion of tetracycline. Thus the abnormalities of gastrointestinal structure and function produced by Billroth -II gastrectomy do not result in impairment of the rate and completeness of tetracycline absorption.
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  • 57
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    Cell & tissue research 186 (1978), S. 551-558 
    ISSN: 1432-0878
    Keywords: C-cells ; Thyroid gland ; Immunocytochemistry ; Calcitonin antibody ; Mammals
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    Topics: Biology , Medicine
    Notes: Summary In the thyroid glands of the horse, pig, deer, mole, and rat, C-cells could be demonstrated by means of the immunocytochemical PAP-technique using rabbit antisera against human calcitonin. Only in ruminants, the crossreaction between the intracellularly stored antigen and the antibodies used appeared to be incomplete.
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  • 58
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    Keywords: Thyroid gland ; Immunocytochemistry ; Thyroglobulin ; Petromyzon marinus L
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    Notes: Summary Antibodies made against thyroglobulin (TG) were used in an immunocytochemical study for the light and electron microscopic localization of TG in the thyroid gland of the anadromous sea lamprey, Petromyzon marinus, during its upstream migration. TG was found in the follicular lumen and in some colloid droplets within the follicular cells. Except for an immunoreactive product observed in a small portion of the interstitial connective tissue, the location of TG in the lamprey was similar to that in the thyroid of the rat.
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  • 59
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    Keywords: Hypothalamus ; Dipnoi (Protopterus) ; Neurohypophysial hormones ; Immunocytochemistry
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    Topics: Biology , Medicine
    Notes: Summary Using the unlabeled antibody peroxidase-antiperoxidase complex (PAP) technique at the light microscopic level, it has been shown that, in the dipnoan preoptico-hypophysial neurosecretory system, vasotocin and mesotocin are synthesized in separate neurons. In the preoptic nuclei, the perikarya of these two types of neurosecretory neurons are not located preferentially. The two types of neurosecretory perikarya give rise to separate vasotocinergic and mesotocinergic axons, respectively. The dipnoan median eminence and neural lobe contain separate vasotocinergic and mesotocinergic nerve fibres, the general distribution of which is described. In the pars distalis and the pars intermedia of the hypophysis, neurohypophysial hormone-containing nerve fibres have not been found.
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  • 60
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    Keywords: Cyproterone acetate ; d-Norgestrel ; Progesterone ; Pars distalis ; adenohypophysis ; Immunocytochemistry ; Dog (Beagle)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The effects of short-term (8 weeks) treatment with different doses of cyproterone acetate (CPA), d-norgestrel (d-N) and progesterone on cells of the pars distalis, as revealed by the immunoperoxidase technique, were studied in cycle-synchronized beagle bitches (first anoestrus). Pituitary glands from non-treated primiparous beagle bitches at the 6th and 9th week of pregnancy were also included. For immunochemical staining specific antisera to the following hormones were used: canine GH, canine PRL, porcine ACTH, bovine TSHβ, bovine LHβ and human FSHβ. Morphological features of high secretory activity in GH cells were evident even after the human oral contraceptive doses of CPA and d-N, and after a dose as low as 0.1 mg/kg/day subcutaneously (s.c.) of progesterone. In contrast, PRL cells did not show any significant treatment-related effects except in those animals which received the highest dose of d-N (0.5 mg/kg/day per os). In this group, as well as in all pregnant bitches, hyperplasia and hypertrophy of PRL cells were found. In the animals treated with the highest doses of CPA (4.0 mg/kg/day per os) and progesterone (42.5 mg/kg/day s.c.) as well as in pregnant bitches, ACTH/MSH and TSH cells showed marked atrophy and regressive changes. Similar morphological signs of depressed secretory activity were also observed in the cells shown to contain FSHβ and/or LHβ as a result of treatment with the highest dose of progesterone and at the 9th week of pregnancy. These structural responses indicate that quantitative and/or qualitative differences may exist between progesterone, the synthetic progesterone derivative CPA and the nortestosterone type progestagen d-N with regard to their effect on pituitary hormone secretion in the beagle bitch.
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    Cell & tissue research 194 (1978), S. 79-102 
    ISSN: 1432-0878
    Keywords: Duodenum ; Endocrine cells ; Differentiation ; Immunocytochemistry ; Electron microscopy
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    Topics: Biology , Medicine
    Notes: Summary The development and cytodifferentiation of endocrine cells that produce the gastrointestinal hormones gastrin, cholecystokinin and secretin have been studied by a combined fluorescence-cytochemical, immunocytochemical and ultrastructural approach. The results show that, during development, several ultrastructurally distinct cell types exhibit COOH-terminal gastrin and cholecystokinin immunoreactivity. Furthermore, some cells simultaneously contain both gastrin- and cholecystokinin-specific antigenic determinants. Studies on the time course of development of gastrin and cholecystokinin cells, together with the above-mentioned data, suggest that gastrin cells may be converted into cholecystokinin cells in development. During this period, gastrin, cholecystokinin and secretin cells store the biogenic monoamine, 5-hydroxytryptamine a feature not displayed by the adult counter-parts of these cells. In the adult duodenum, characteristic enterochromaffin (EC) cells store 5-hydroxytryptamin for which, evidence for a possible hormonal role has been presented. Taken together, our data indicate that the differentiation of duodenal endocrine cells occurs in distinct steps, each involving a restriction in the biosynthetic repertoire of the cell.
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  • 62
    ISSN: 1432-0878
    Keywords: Pancreas ; Gut ; Pancreatic polypeptide (PP) cells ; Immunocytochemistry ; Ultrastructure
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    Topics: Biology , Medicine
    Notes: Summary Pancreatic polypeptide (PP) cells in the pancreas and gut of chickens were studied by immunocytochemistry. In the pancreas PP cells were numerous and disseminated in the exocrine parenchyma. In this location they were first seen at the 9th day of incubation, i.e. several days after the appearance of glucagon, insulin and somatostatin cells. Very large numbers of these cells occurred from about the 14th day until shortly after hatching when the PP cell frequency was somewhat reduced. At the 17th day of incubation PP cells appeared in the duodenum. Subsequently the number of PP cells in the duodenum increased, and PP cells began to appear also in the jejunum-ileum (19th day) and in the proventriculus and colon (21st day). At hatching and a few days thereafter, PP cells were relatively numerous in the small intestines but much less frequent in the proventriculus and colon. One week after hatching PP cells had disappeared from the colon but remained in the proventriculus and small intestines. Ultrastructurally the PP cell was clearly distinguishable from the insulin, glucagon and somatostatin cells. It was characterized by the presence of spherical cytoplasmic granules which were membrane-bound and moderately electron dense. Areas of firm adhesion between PP cells and acinar cells in the form of desmosomes and possibly also gap junctions were observed.
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  • 63
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    Keywords: Pituitary gland ; Mexican axolotl ; Prolactin ; Somatotropin ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The indirect immunofluorescence procedure was used to identify prolactin (LTH)-and somatotropin (STH)-producing cells in the pituitary of the Mexican axolotl. Histological staining techniques were employed to corroborate immunocytological results. The LTH cells are large, orange-staining cells (acidophils 1) distributed in the posterior two-thirds of the pars distalis. The STH cells are small, erythrosinophilic elements (acidophils 2) principally concentrated in the dorsal part of the pars distalis.
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  • 64
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    Cell & tissue research 190 (1978), S. 151-161 
    ISSN: 1432-0878
    Keywords: Pituitary gland ; Rhesus monkey ; Immunocytochemistry ; Luteinizing hormone ; Thyroid stimulating hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Pituitary glands from juvenile (pre-pubertal) and adult male and female rhesus monkeys were examined following immunocytochemical staining with antisera to the beta subunits of ovine luteinizing hormone (LHβ) and of human thyroid stimulating hormone (TSHβ). The LHβ antiserum reacts with a cell that is PAS-positive, occurs singly and is randomly distributed throughout the pars distalis. The diameter of these cells is approximately 11.5 μm. They do not seem to vary in number in either juveniles (pre-pubertals) or adults, or in males or females. There appears to be fewer LH cells in the pituitary glands of pregnant and lactating females. In addition to staining cells in the pars distalis, the antiserum also reacts with a population of cells located in the pars tuberalis. The cells that stain with the anti-TSHβ serum are confined primarily to the pars distalis. They are approximately 15.8 μm in diameter and are generally found in groups or clusters located in the anterior and medial regions of the gland. The TSH cells vary in number from one animal to another; however, this variability is unrelated to the age or the sex of the animals. No demonstrable changes occur in the number of TSH cells during pregnancy or lactation.
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    Cell & tissue research 193 (1978), S. 211-218 
    ISSN: 1432-0878
    Keywords: 17β-estradiol ; Pituitary gland ; Dog (Beagle) ; Immunocytochemistry ; Glycoprotein hormones (FSH, LH, TSH)
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    Topics: Biology , Medicine
    Notes: Summary The effect of long-term treatment (52 weeks) with high doses of 17β-estradiol (1.28 mg/kg/week intramuscularly) on gonadotrophs was studied in the pituitary gland of the beagle bitch. For immunochemical staining the immunoperoxidase technique and antisera to the specific beta (β) subunits of FSH and LH were employed. For control purposes antisera to the following hormones were also used: bovine TSHβ, canine GH, canine PRL and porcine ACTH1. In the pars distalis and pars tuberalis of control bitches, in addition to the cells which react solely with antisera to either LHβ or FSHβ, most cells were reactive to both antisera. The cells stained for FSHβ were less numerous than those shown to contain LHβ. TSHβ, PRL, GH and ACTH/MSH were localized in distinctly different cell types in the pars distalis of all control animals. In the treated bitches, almost complete regression of cells classically identified as gonadotrophs and stained for LHβ was observed. On the other hand, using the antiserum to FSHβ, selective immunochemical staining was localized in cells fitting the morphological characteristics of TSH cells. All these cells were also stained for TSHβ. However, a few cells were also shown to react solely with the antiserum to TSHβ. These cells, which seem to contain both TSHβ and FSHβ, were further clearly differentiated from PRL, GH and ACTH/MSH cells on the basis of their cytological features, intraglandular distribution and by immunochemical double staining. These observations support the concept that the one cell-one hormone theory may not necessarily apply to the glycoprotein hormones of the dog pituitary gland.
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    Cell & tissue research 194 (1978), S. 327-336 
    ISSN: 1432-0878
    Keywords: Prolactin ; Growth hormone ; Ovine pituitary ; Immunocytochemistry ; Granule size
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    Topics: Biology , Medicine
    Notes: Summary Using the peroxidase-antiperoxidase immunocytochemical staining technique, prolactin and growth hormone cells have been identified and described in the ovine pituitary. The image analysing computer, Quantimet 720, was used to assess accurately the size range of the secretory granules in these cell types. The area size distributions of the prolactin and growth hormone granules are similar. An increased proportion of larger granules was observed in the prolactin cells post-partum. Serial sections stained alternately for prolactin or growth hormone confirmed that the cells contain either prolactin or growth hormone but not both.
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    Cell & tissue research 195 (1978), S. 183-187 
    ISSN: 1432-0878
    Keywords: Somatostatin-containing neurons ; Hypothalamus ; Median eminence ; Immunocytochemistry ; Domestic mallard
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    Topics: Biology , Medicine
    Notes: Summary In the hypothalamus of the adult domestic mallard, small to medium-sized perikarya are stained specifically with rabbit antiserum against cyclic somatostatin (PAP technique of Sternberger). The somatostatin-immunoreactive material is located in neurons different from those containing immunoreactive LHRH, vasotocin or mesotocin. Somatostatin-containing perikarya are observed 1) in a chain-like arrangement extending from the area of the median division of the supraoptic nucleus to the caudal end of the paraventricular nucleus; 2) as single cells in the preoptic region; and 3) as a conspicuous formation in the optic tract division of the supraoptic nucleus. In the rostral portion of the median eminence, somatostatin-immunoreactive axons penetrate into the external zone. Fine accessory fiber bundles project to the neural lobe.
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  • 68
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    Cell & tissue research 186 (1978), S. 393-398 
    ISSN: 1432-0878
    Keywords: β-Lipotropin ; Hypothalamus ; Hypophysial portal capillaries ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary β-Lipotropin (β-LPH) has been localized in hypothalamus and pituitary of sheep and ox by the immunoperoxidase technique. In both species β-LPH was found in perikarya of arcuate neurons as well as in cells of the anterior and intermediate lobes of the pituitary. A large number of immunoreactive axons were found in the arcuate region; some appeared to innervate other neurons and others projected to portal capillaries. Stained fiber segments were also scattered throughout the hypothalamus. The presence of β-LPH in hypothalamic neurons supports the possibility that brain β-LPH may be a precursor for opiate-like or other peptides which may be involved in neuromodulation or neurohormonal activities.
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  • 69
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    Calcified tissue international 24 (1977), S. 223-229 
    ISSN: 1432-0827
    Keywords: Enamel-cementum-morphology ; Immunocytochemistry ; Biochemistry
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    Topics: Biology , Medicine , Physics
    Notes: Summary The continuously erupting rabbit incisor tooth is normally thought of as having an enamel covered “crown” on its labial surface and a cementum covered “root” on its lingual surface. We have examined both surfaces of continuously erupting rabbit incisor teeth taken from near term embryos by a variety of means, including transmission and scanning electron microscopy, biochemical fractionation, and immunohistochemistry. In all cases, we could detect no qualitative difference in the early extracellular matrices taken from the labial and lingual surfaces of the teeth. Both matrices were shown to be composed of dentin and enamel, although the thickness and geometry of the enamel matrix on the lingual surface was somewhat different from that on the labial surface.
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  • 70
    ISSN: 1432-1041
    Keywords: Cefoxitin ; lidocaine ; intramuscular ; bioavailability ; pain
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The use of lidocaine HCl solution at concentrations of 0.5 and 1.0% to reconstitute sodium cefoxitin relieves the pain associated with intramuscular injections of the antibiotic. Cefoxitin absorption by the intramuscular route is initially rapid and is virtually complete. Peak serum concentrations, corresponding to about one-half those of a comparable intravenous infusion, are achieved in 30 min. Continuing absorption tends to maintain higher serum concentrations for longer times. Renal clearance and serum half-life of cefoxitin do not appear to be affected by lidocaine at its effective anaesthetic concentrations.
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    European journal of clinical pharmacology 12 (1977), S. 69-72 
    ISSN: 1432-1041
    Keywords: Metronidazole ; serum concentration ; bioavailability ; food intake ; healthy subjects ; Crohn's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The possible influence of food intake on the bioavailability of metronidazole was examined in ten healthy volunteers by administration of a single dose of metronidazole on an empty stomach, and with a standardized breakfast. Food intake did not significantly alter the bioavailability of metronidazole. The interindividual variation in bioavailability appeared to be slight. In nine patients with Crohn's disease, the absorption of metronidazole appeared to be reduced and to be more variable than in healthy subjects. In both groups there was a clear relationship between the amount absorbed and dose/kg body weight. Thus, from the pharmacokinetic point of view, metronidazole can safely be given either with or between meals. The dose should be related to body weight.
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    European journal of clinical pharmacology 12 (1977), S. 285-290 
    ISSN: 1432-1041
    Keywords: Phenytoin acid ; phenytoin calcium ; bioavailability ; inequivalence of generics ; normal subjects ; volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum phenytoin concentrations have been studied in epileptic patients and healthy subjects taking tablets of phenytoin calcium (Desitin), A, phenytoin acid (Desitin), B, and phenytoin acid (Nordmark), C. Retrospective data and prospective investigation of hospitalized patients on long-term phenytoin treatment showed that significantly higher serum concentrations of phenytoin were produced by the phenytoin acid preparations B and C than by the phenytoin calcium preparation A. In a cross over study six volunteers received 200 mg/day of preparations A, B, and C for three weeks. In this study, too, higher phenytoin serum concentrations were produced by B and C than by A, although the differences were not statistically significant. The reasons for the discrepancies between the studies in healthy and epileptic subjects are discussed.
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  • 73
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    European journal of clinical pharmacology 12 (1977), S. 383-386 
    ISSN: 1432-1041
    Keywords: Benzodiazepine ; temazepam ; pharmacokinetics ; bioavailability ; hard and soft gelatine capsules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels of temazepam were determined in healthy subjects after single oral administration of soft and hard gelatin capsules, and after 7 consecutive night-time doses in soft capsules. Absorption from soft gelatin capsules was significantly faster and produced earlier and higher peak plasma levels. The two pharmaceutical forms did not show any significant difference in relative availability. The apparent half-life of temazepam after night-time administration was significantly shorter than after morning administration, but no change in half-life was observed between the first and seventh night-time doses.
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  • 74
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    European journal of clinical pharmacology 11 (1977), S. 277-281 
    ISSN: 1432-1041
    Keywords: Proscillaridin ; oral administration ; portal venous sample ; porto-peripheral concentration difference ; bioavailability ; 86Rb-uptake inhibition assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of proscillaridin A was studied in four patients undergoing catheterization of the portal vein for diagnostic purposes. Proscillaridin 1.5 mg was given as a single oral dose and plasma glycoside activity was analyzed by the86Rb-uptake inhibition technique. Proscillaridin appeared rapidly in the portal blood, peak activity being found after 15 min in three and after 30 min in one patient. In peripheral blood the peak activity occurred after approximately 35 min. Despite rapid passage across the gut wall, porto-peripheral differences in glycoside activity were small; they were zero after 4 h. The mean amount absorbed as active proscillaridin during the first 4 h after the dose was calculated to be only 7.1% of the given amount. Late porto-peripheral differences, probably due to enterohepatic recycling, appeared after 6 h in three patients. The results suggest that proscillaridin undergoes first pass inactivation in the gut wall. Enterohepatic recirculation may contribute to the amounts of active glycoside that reach the systemic circulation.
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  • 75
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    European journal of clinical pharmacology 11 (1977), S. 207-212 
    ISSN: 1432-1041
    Keywords: Chlorpropamide ; hypoglycaemic agent ; bioavailability ; plasma concentrations ; bioequivalence ; dissolution tests
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of chlorpropamide from two new formulations (Melitase® tablets) has been compared to that from a reference formulation which is currently in clinical use as a hypoglycaemic agent. In both rate and extent of bioavailability, all three formulations may be considered equivalent, providing allowances are made for differences in drug content. With 95% confidence, the mean bioavailability of chlorpropamide from the new formulations was within about 16% of the mean from the reference formulation, and formulation-related differences were not statistically significant. Although all three formulations were shown to have similar dissolution profiles, dissolution of chlorpropamide was pH-dependent in vitro. Dissolution was almost complete during 30 min at pH 7.2, but only 40%–60% had dissolved during 90 min at pH 2.0. A peak mean concentration of 22.7 µg/ml was reached 3 h after administration of 2×100 mg tablets of the new formulation and peak mean concentrations of 26.8 µg/ml and 27.4 µg/ml were reached 3 h and 4 hours after administration of one 250 mg tablet of the new formulation and one 250 mg tablet of the reference formulation respectively. Formulation-related differences of mean plasma concentrations (after scaling for equal doses of 250 mg) were not significant and each formulation provided similar plasma concentrations at corresponding times after administration. Statistically significant subject-related differences in all the parameters of bioavailability were shown by analyses of variance.
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  • 76
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    European journal of clinical pharmacology 11 (1977), S. 219-224 
    ISSN: 1432-1041
    Keywords: Nortriptyline ; 10-OH-nortriptyline ; bioavailability ; plasma metabolites ; first pass metabolism ; oral dose ; intramuscular dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nortriptyline was given orally and intramuscularly to six depressed patients. Plasma concentrations of parent drug and the unconjugated and conjugated principal metabolite, 10-hydroxynortriptyline, were determined by mass fragmentography. There was a significant decrease in the area under the nortriptyline plasma concentration — time curve after the oral route of administration, whilst the elimination rate was unchanged. With the oral dose, plasma concentrations of the metabolites were higher and peaked earlier than after intramuscular administration, whilst the opposite was true for the parent compound. This proves that the difference in bioavailability between the two routes of administration was due to first pass metabolism. As determined from the ratio between corresponding areas, the relative bioavailability of the oral dose was 66±21 S.D. per cent. This fraction is higher than that reported previously when intravenous nortriptyline was used as the reference dosage form.
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  • 77
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    European journal of clinical pharmacology 12 (1977), S. 281-284 
    ISSN: 1432-1041
    Keywords: Tetracycline ; bioavailability ; plasma levels ; nutritional state ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Relative bioavailability after oral administration of a single dose and Cmin levels of tetracycline in plasma after multiple doses were determined in groups of well-nourished and undernourished subjects. The relative bioavailability of tetracycline, assessed by the area under serum concentration time-curves, did not differ in undernourished and well-nourished patients. The plasma levels were not different in the two groups after the conventional dose of tetracycline HCl 250 mg at 6 hour intervals. However, in these studies undernourished subjects received a higher dose per kg body weight, which could have compensated for any effect of a shortened half life of the drug. When the dose per kg body weight was reduced, the Cmin levels were lower. On the other hand, with the same dose per kg body weight at more frequent intervals, the plasma concentrations were similar to those in well-nourished subjects. These studies indicate that the dosage regimen should be based both on body weight and on the nutritional status of the individual.
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  • 78
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    European journal of clinical pharmacology 12 (1977), S. 65-68 
    ISSN: 1432-1041
    Keywords: Indomethacin ; antacids ; drug-drug interactions ; bioavailability ; drug combinations
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The biovailability of indomethacin from two indomethacin-antacid (aluminum hydroxide magnesium carbonate and magnesium hydroxide) combinations was compared with the bioavailability of oral indomethacin. Relative bioavailability was estimated by three methods: comparison of plasma concentrations at various times, comparison of areas under plasma concentration time curves, and comparison of the amount of drug excreted unchanged in the urine. A double blind three-way crossover study was conducted in twelve healthy volunteers. The combination with the slightly smaller amount of antacid (preparation A) showed significantly decreased bioavailability by all three methods in comparison with indomethacin alone (preparation C). The combination with the larger amount of antacid (preparation B) was also less bioavailable than preparation C. This effect was significant only for the comparison of areas under curves and not for plasma levels, although the mean plasma levels produced by preparation B at all times were lower than those for preparation C. These findings suggest that aluminum hydroxide magnesium carbonate and magnesium hydroxide decrease the bioavailability of indomethacin.
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  • 79
    ISSN: 1432-1041
    Keywords: Tolmetin ; pharmacokinetics ; bioavailability ; antacid ; oral dose
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The purpose of this study was to determine whether a concomitant single dose of antacid or multiple doses of antacid administered prior to, and with tolmetin, alter the pharmacokinetics of tolmetin when the drug was administered as a commercially available tablet containing tolmetin sodium. The possible effects of the antacid on plasma concentrations and urinary excretion of tolmetin and its major metabolite were evaluated following administration of: (a) tolmetin sodium alone; (b) antacid four time a day for three days prior to a single dose of tolmetin sodium, with continuation of the antacid during the day tolmetin was given; and (c) co-administration of single doses of tolmetin sodium and antacid. The twenty-four subject study was of the crossover type. There were no significant differences among treatment means for: (i) peak plasma concentrations of both tolmetin and metabolite, (ii) AUC 0–8 h and AUC 0-∞ for both tolmetin and metabolite, (iii) time to peak plasma concentration for both tolmetin and metabolite, (iv) plasma concentrations of both tolmetin and the metabolite at all sampling times (except for tolmetin at 2 h), (v) renal clearance of both tolmetin and its metabolite, and (vi) the amount of metabolite excreted in the 0–24 h urine. There were small, but significant, differences among amounts of tolmetin excreted in the 0–24 h urine. Semilogarithmic plots of both tolmetin and metabolite plasma concentrations past the peak concentrations were curved over the entire 8-h observation period; although the elimination half-life of tolmetin has been reported to be about one hour, the half-life most probably exceeds 2.6 h in most subjects. The results of this study indicate a lack of a significant drug-drug interaction between the non-steroidal anti-inflammatory agent, tolmetin sodium, and a commonly used antacid, which is a mixture of magnesium and aluminium hydroxides.
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  • 80
    ISSN: 1432-1041
    Keywords: Coumarin ; 7-Hydroxycoumarin ; drug disposition ; first-pass effect ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of coumarin (C) upon i.v. and p.o. administration and its metabolites 7-hydroxy-coumarin (7-HC) and 7-hydroxy-coumarin glucuronide (7-HCG) have been studied. Six healthy volunteers were involved in this investigation. Four of the volunteers participated in a crossover study. Coumarin was administered i.v. and p.o. in dose sizes of 0.25 mg/kg and 0.857 mg/kg, respectively. Coumarin is rapidly absorbed p.o., however the availability to systemic circulation is less than 4%. The rest of the dose appears quantitatively as 7-HC and 7-HCG in systemic circulation suggesting an extensive firstpass effect. Coumarin and 7-HCG are best fitted to an open two-compartment model, whereas 7-HC is best fitted to an open one-compartment model. The biological half-life of both C (0.80 vs. 1.02 h) and 7-HCG (1.47 vs. 1.15 h) was not significantly different for the two routes of administration. The large total clearance of C again suggests a first-pass effect; while that of 7-HCG, which is nearly exclusively eliminated into urine, indicates active tubular secretion of the glucuronide.
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  • 81
    ISSN: 1432-0878
    Keywords: Pituitary ; Dexamethasone ; ACTH ; Autoradiography ; Immunocytochemistry
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    Topics: Biology , Medicine
    Notes: Summary 3H-Dexamethasone (10 μg/kg) was injected intravenously in adrenalectomized rats and after survival times of 5, 30, 60, and 180 min its uptake within the pituitary was studied by autoradiography. Radioactivity was concentrated in cell nuclei in the pars nervosa and pars distalis. Within the pars intermedia, only cells of the marginal zone were labeled. In the pars distalis, some cells showed a weak nuclear accumulation of radioactivity as early as 5 min after injection. The tissue radioactivity was nearly maximal at 5 min, and the proportion of radioactivity in nuclei reached a maximum of 60–70% by 30 min. In competition experiments, non-radioactive steroids (1 mg/kg) were injected 5 min before 3H-dexamethasone and sacrifice was 30 min later. Dexamethasone markedly diminished the nuclear accumulation in the pars distalis, but corticosterone and progesterone did not. In the pars nervosa, corticosterone and progesterone competed for nuclear uptake of 3H-dexamethasone, although less effectively than dexamethasone itself. Different cell types in the pars distalis were characterized by treating autoradiograms with an immuno-peroxidase bridge procedure. Cells treated with anti-ACTH 17–39 had the greatest nuclear concentration of radioactivity, and those stained with anti-TSH were least heavily labeled. Cells treated with antisera to GH, PRL, and hCG were moderately labeled.
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  • 82
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    Cell & tissue research 178 (1977), S. 17-38 
    ISSN: 1432-0878
    Keywords: Myosin ; Immunocytochemistry ; Adrenal medulla ; Exocytosis ; Secretion
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    Topics: Biology , Medicine
    Notes: Summary Myosin was isolated in high purity from the bovine adrenal medulla by gel filtration and ion exchange chromatography. The purified myosin was analyzed by electrophoresis in gels containing SDS and found to contain a 200,000 molecular weight heavy chain and major light chains of molecular weights 20,000 and 17,000 in a 1∶1∶1 molar ratio. At high ionic strength the myosin had high Ca-ATPase and K-EDTA-ATPase activities and low Mg-ATPase activity. At low ionic strength, the Mg-ATPase was activated to a low level by rabbit muscle actin. The myosin was found to decorate F-actin in the absence, but not the presence of ATP. In low ionic strength solutions, the myosin assembled into characteristic bipolar filaments. The distribution of this myosin in the adrenal medulla and of cross-reacting myosin in several other bovine tissues was determined with the use of antimedullary myosin immunoglobulin G as a specific stain that was detected by direct and indirect immunofluorescence. In the medulla strong staining was seen between the chords of chromaffin cells indicating the presence of a highly muscular vasculature that may perform functions analogous to those of the myoepithelium of exocrine glands. The chromaffin cells showed weak positive staining around the nuclei and in a pattern radiating toward adjacent blood vessels. Cells of the inner zone of the adrenal cortex showed strong staining in the peripheral cytoplasm while cells in the intermediate and outer zones did not stain. In a blood smear, platelets and the cytoplasm of leukocytes stained strongly while erythrocytes did not stain. In striated muscle and the gray and white matter of the cerebrum only the capillaries and larger vessels stained. In the liver the phagocytic cells bordering vascular sinuses stained strongly while the hepatocytes were separated from one another by a 2 micron trilaminar band possibly representing the microfilament web surrounding the bile canaliculi and associated with junctional complexes. The results suggest that myosin is present in several highly differentiated, non-motile tissue cells where it may play a role in secretion or other specialized functions.
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  • 83
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    Cell & tissue research 185 (1977), S. 465-479 
    ISSN: 1432-0878
    Keywords: Somatostatin cells ; Pancreas ; Gut ; Immunocytochemistry ; Comparative study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Somatostatin cells are numerous in the pancreas and digestive tract of mammals as well as birds. In the pancreas of chicken, cat and dog they occur in both the exocrine parenchyma and in the islets. In the rat and rabbit, somatostatin cells have a peripheral location in the islets, whereas in the cat, dog and man the cells are usually more randomly distributed. In the stomach of rabbits and pigs, somatostatin cells are more numerous in the oxyntic gland area than in the pyloric gland area, whereas the reverse is true for the cat, dog and man. In the cat, pig and man, somatostatin cells are fairly numerous in the duodenum, whereas in the rat, rabbit and dog they are few in this location. In the remainder of the intestines somatostatin cells are few but regularly observed. Somatostatin cells are numerous in the human fetal pancreas and gut. In the fetal rat, somatostatin cells first appear in the pancreas and duodenum (at about the 16–17th day of gestation) and subsequently in the remainder of the intestine. Somatostatin cells do not appear in the gastric mucosa until after birth. Three weeks after birth, somatostatin cells show the adult frequency of occurrence and pattern of distribution. In the chicken, somatostatin cells are numerous in the proventriculus, absent from the gizzard, abundant in the gizzard-duodenal junction (antrum), infrequent in the duodenum and virtually absent from the remainder of the intestines. No immunoreactive cells can be observed in the thyroid of any species nor in the ultimobranchial gland of the chicken. In the chick embryo, somatostatin cells are first detected in the pancreas and proventriculus (at about the 12th day of incubation). They appear in the remainder of the gut much later, in the duodenum at the 16th day, in the antrum at about the 19th day and still later in the lower small intestine. The ultrastructure of the somatostatin cells was studied in the chicken, rat, cat and man; the cells were identified by the consecutive semithin/ultrathin section technique. The somatostatin cells display the properties of the D cell. There was no difference in granule ultrastructure between somatostatin cells in the gut and the pancreas. The granules, which are the storage site of the peptide, are round, supplied with a tightly fitting membrane and have a moderately electron-dense, fine-granulated core. The mean diameter of the somatostatin granules is smallest in rat (155–170 nm) and largest in the chicken (270–290 nm).
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  • 84
    ISSN: 1573-8744
    Keywords: accelerated convergence method to estimate AUC0-∞ and A e ∞ ; bioavailability ; estimation of total areas ; estimation of total amounts excreted ; blood sampling schemes for digoxin ; elimination half-life of digoxin ; intra- and interindividual variation of renal clearance of digoxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Five methods are compared to estimate the total area under the digoxin plasma or serum concentrationtime curve (AUC0-∞) after a single dose of drug. To obtain accurate estimates of AUC0-∞, data required are concentrations at a sufficient number of sampling times to define adequately the concentration-time curve prior to the log-linear phase, and at least three, but preferably four or more equally spaced points in the terminal loglinear phase. One method (designated Method I) requires a digital computer; another (Method III) is the classical method (these two methods do not require equally spaced points in the loglinear phase). Method IIA is the accelerated convergence method of Amidon et al.; Methods IIB and IIC are modifications of this method, but incorporate usual and orthogonal least squares, respectively, which make them more accurate with real (noisy) data. Methods I and IICgave very comparable estimates of AUC0-∞. Results indicate that digoxin administered orally in aqueous solution was completely (100%) absorbed when bioavailability estimates were based on oral and intravenous AUC0-∞ estimates and the actual doses, whereas formerly only about 80% absorption was reported, based on areas, under plasma concentration curves which were truncated at 96 hr. It is shown that the sampling scheme of blood can produce biased apparent bioavailability estimates when areas under truncated curves are employed, but an appropriate sampling scheme and application of method IIyield accurate bioavailability estimates. This is important particularly in those bioavailability studies where one is attempting to determine the appropriate label dose for a new “fastrelease” digoxin preparation relative to the label dose and bioavailability of currently marketed tablets. It is shown that the magnitudes and variability of apparent elimination rate constants and halflives of digoxin, estimated from urinary excretion data by the σ− method, depend on which value of A e ∞ is used. The formerly reported greater interindividual variability of AUC data compared to At data for digoxin is explained in that the AUCs, but not the Ae,'s, involve the renal clearance, which exhibits considerable inter- and intraindividual variation.
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  • 85
    ISSN: 1573-8744
    Keywords: aspirin ; dissolution ; bioavailability ; effect of antacids ; acid ; capacity ; consuming ; in vivo ; buffering effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The in vitrodissolution profile, in vitroand in vivobuffering characteristics, and single-dose bioavailability of various buffered aspirin tablet formulations were studied. Buffering agents,such as magnesium and aluminum hydroxides (formulations B and C) or magnesium carbonate and aluminum glycinate (formulation D), significantly increased the rate of aspirin dissolution from solid dosage forms as compared to an unbuffered tablet (formulation A). The extent of aspirin absorption was equivalent with all formulations;however, the faster rate of dissolution (t50 and t90)with buffered formulations resulted in earlier and higher peak concentration of salicylate compared to that with unbuffered formulation, following a two-tablet dose in the fasting state. A comparison of the in vivobuffer capacity of a four-tablet dose of formulations B and D was performed in the postcibal state at the time of maximal meal-induced acid secretion, using a radiotelemetry procedure for determination of pH. Formulation B prolonged the interval of elevation of intragastric pH 〉 3 for 32 min as compared to 12 min for D.
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  • 86
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    Journal of pharmacokinetics and pharmacodynamics 5 (1977), S. 133-146 
    ISSN: 1573-8744
    Keywords: bioavailability ; phenytoin sodium capsules ; plasma levels ; human studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Eleven single lots of 100-mg phenytoin sodium capsules were evaluated for their relative bioavailability in 12 normal human volunteers. These products were manufactured by eight different companies and met all compendial specifications. The products were evaluated with respect to plasma levels at various times up to 96 hr following administration of single 100-mg doses, times of peak level, peak plasma concentrations, and areas under the plasma level—time curve. Several of the products exhibited statistically significant differences in the various parameters studied.
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  • 87
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    Journal of pharmacokinetics and pharmacodynamics 5 (1977), S. 183-192 
    ISSN: 1573-8744
    Keywords: propranolol ; kinetics ; volunteers ; bioavailability ; threshold dose
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of propranolol in blood was studied in healthy volunteers, following intravenous administration of 0.1 mg/kg and increasing oral doses of 10,20, and 40 mg, using a specific and sensitive gas Chromatographie method. The systemic availability of orally administered propranolol varied from 9% to 38% between subjects, but it was constant within each subject. A linear relationship was found between the area under the blood concentration-time curve and the oral dose. At variance with literature data, we could not observe a threshold dose.
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  • 88
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    Cell & tissue research 177 (1977), S. 317-323 
    ISSN: 1432-0878
    Keywords: Hypothalamus ; Lamprey ; Vasotocinergic system ; Adenohypophysis ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary With the use of the unlabeled antibody peroxidase-antiperoxidase (PAP) technique at the light microscopic level, it was shown that the preoptico-hypophysial neurosecretory system of the adult migrating Lampetra fluviatilis is a vasotocinergic system. It does not synthesize vasopressin. The results are entirely consistent with earlier chromatographic and pharmacological indications that it produces little or no oxytocin-like peptide hormone. In the adenohypophysis, immunoreactive neurohypophysial peptidergic fibres are absent.
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  • 89
    ISSN: 1432-0878
    Keywords: Pars intermedia of hypophysis ; Rana temporaria ; Mesotocinergic and vasotocinergic fibres ; Immunocytochemistry ; Electron microscopy
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    Topics: Biology , Medicine
    Notes: Summary With the use of the unlabeled antibody peroxidase-antiperoxidase (PAP) method at the electron microscopic level, it has been shown that the pars intermedia of the hypophysis of Rana temporaria contains a diffuse intercellular network of separate mesotocinergic and vasotocinergic nerve fibres.
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  • 90
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    Cell & tissue research 179 (1977), S. 211-224 
    ISSN: 1432-0878
    Keywords: Somatostatin (rat) ; Hypothalamus ; Fibers and perikarya ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Using the immunoenzyme bridge-technique at the light and electron microscopic levels, somatostatin can be demonstrated in the perikarya of the anterior periventricular nucleus, in the median eminence and in the parvocellular hypothalamic nuclei of the rat. In the latter regions the perikarya are negative, whereas a positive reaction for somatostatin is found in a delicate network of fibers and middle-sized granules of very small axons. In light of these results, the double function of somatostatin — as release inhibiting hormone and as transmitter — is discussed. The positive staining reaction in the organum vasculosum laminae terminalis of male and female rats as well as in the subfornical organ, the nucleus dorsalis thalami and the nucleus medialis habenulae in female controls and pregnant rats is not due to somatostatin-containing structures, but partly to substance P and partly to a substance which could not be defined.
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  • 91
    ISSN: 1432-0878
    Keywords: External region of median eminence (Rat) ; Vasopressinergic and oxytocinergic fibres ; Hypothalamic lesions ; Adrenalectomy ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The origin of the vasopressinergic and oxytocinergic nerve fibres of the external region of the rat median eminence was investigated by means of hypothalamic lesions, adrenalectomy and immunocytochemistry. The results obtained in bilaterally adrenalectomized animals with complete, or incomplete, destruction of the suprachiasmatic nuclei showed that, at least, the great majority of the vasopressinergic and oxytocinergic nerve fibres of the external region of the rat median eminence do not originate from the suprachiasmatic nuclei. From the observations obtained in bilaterally adrenalectomized animals with total or subtotal destruction of both paraventricular hypothalamic nuclei, it appears that the paraventricular nuclei must be the origin of (nearly) all the vasopressinergic and oxytocinergic nerve fibres of the external region of the rat median eminence. The results strongly suggest that both types of fibres originate from all parts of the paraventricular nuclei.
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  • 92
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    Cell & tissue research 180 (1977), S. 491-503 
    ISSN: 1432-0878
    Keywords: Pig ; Oxytocin ; [8-Lysine]-Vasopressin ; Specific localization ; Immunocytochemistry ; One hormone, One Neurophysin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Synthetic oxytocin and [8-arginine]-vasopressin conjugated to bovine thyroglobulin were used to induce specific antibodies in rabbits. The specificity of the anti-oxytocin serum, and the suitability of the anti-[8arginine]-vasopressin serum for the detection of [8-lysine]-vasopressin, was evaluated by immunofluorescent studies of the respective hormones bound to Sepharose 4B particles. Oxytocin and [8-lysine]-vasopressin were specifically localized in the paraventricular (PVN) and supraoptic (SON) nuclei of the pig hypothalamus using the immunoperoxidase staining technique. After an examination of serial transverse and sagittal sections stained for either of the hormones we observed that: 1. In the rostral SON, oxytocin and vasopressin containing neurons were uniformly distributed; 2. In the caudal SON, most of the neurons contained oxytocin, but there were still a few ‘vasopressin’ neurons; 3. In the rostral PVN, the two hormones were evenly spread in neurons close to the third ventricle; 4. In the caudal PVN, the oxytocin and vasopressin containing neurons were differentially distributed, with ‘oxytocin’ neurons adjacent to the third ventricle, and ‘vasopressin’ neurons lateral to these and concentrated in the dorso-caudal PVN. In the cells of the PVN, there was evidence that the distribution of oxytocin and vasopressin is similar to the distribution of porcine neurophysin-II and porcine neurophysin-I respectively. This similarity is consistent with the one hormone — one neurophysin concept in the pig.
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  • 93
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    Cell & tissue research 184 (1977), S. 15-27 
    ISSN: 1432-0878
    Keywords: Human hypothalamus ; Magnocellular neurosecretory nuclei ; Suprachiasmatic nuclei ; Vasopressinergic and oxytocinergic neurons ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The human hypothalamic-neurohypophysial hormone-producing nuclei were investigated with the unlabeled antibody peroxidase-antiperoxidase complex (PAP) technique at the light microscopic level. The size, shape and location of the supraoptic, paraventricular, accesssory supraoptic and suprachiasmatic nuclei were determined. It was demonstrated in the human hypothalamus, as well as in the hypothalamus of other mammals, that vasopressin and oxytocin are synthesized in separate neurons. In each of the nuclei of the magnocellular neurosecretory system, the distribution, ratios and structural features of the vasopressinergic and oxytocinergic neurons were determined. It was shown that the human suprachiasmatic nuclei contain numerous neurophysin-vasopressin-producing neurons.
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  • 94
    ISSN: 1432-0878
    Keywords: Endocrine cells ; Gut ; Neurotensin ; Immunocytochemistry ; Comparative studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Endocrine cells displaying neurotensin immunoreactivity are found scattered in the jejuno-ileum of all mammals studied, including man. They are rather scarce in rat, guinea pig, rabbit and pig and fairly numerous in cat, dog and man. In most mammals the neurotensin cells predominate on the villi. Only in the dog are they more numerous in the crypts. In the chicken, neurotensin cells occur all along the intestinal tract. They are particularly numerous in the zone that joins the gizzard with the duodenum. The ontogeny of the neurotensin cells in the gut was studied in rats and chickens. In the rat, the cells are first observed in the jejuno-ileum immediately before birth. The adult frequency is reached 4–5 days later. In the chicken, neurotensin cells first appear in the colon in the 18 day old embryo and in the small intestine two days later (i.e. one or two days before hatching). A few days after hatching, the gut has achieved the adult number of neurotensin cells per unit area.
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  • 95
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    Cell & tissue research 184 (1977), S. 491-497 
    ISSN: 1432-0878
    Keywords: Somatostatin ; Immunocytochemistry ; Human hypothalamus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In order to identify clearly the nervous structures containing somatostatin in the human hypothalamus, an immunohistochemical localization of this neurohormone was performed at light-microscopic level. Using a antiserum specific to somatostatin and the unlabeled antibody peroxidase-antiperoxidase technique, we have found somatostatin in neurons with cell bodies in an area in the anterior hypothalamus corresponding to the infundibular nucleus. Somatostatin-containing fibers were also detected in the neurovascular zone of the pituitary stalk, suggesting that somatostatin is released in that region to reach the capillaries in the pituitary portal plexus. A large bundle of somatostatin fibers extending from the anterior part of the paraventricular nucleus up to the posterior portion of the mammillary bodies has also been detected. The role of these fibers still remains to be clarified.
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  • 96
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    Cell & tissue research 183 (1977), S. 177-189 
    ISSN: 1432-0878
    Keywords: Cyproterone acetate ; Pars distalis ; Adenohypophysis ; Immunocytochemistry ; Dog (Beagle)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The effects of oral administration of 100 mg per kg per day cyproterone acetate (CPA) for four weeks on cells of the pars distalis, as revealed by the immunoperoxidase technique and chemical staining, were studied in the ovariectomized beagle bitch. For immunochemical staining antisera to the following hormones were used: canine GH, canine PRL, porcine ACTH, bovine TSHβ, bovine LHβ and human FSHβ1. The most striking effects of the treatment were an overall increase in the relative proportion of GH cells and a marked morphological indication of high secretory activity in these cells. In contrast, PRL cells were not affected significantly. In all ovariectomized control bitches a marked atrophy of the cells stained for FSHβ (FSH cells) and hypertrophy of the cells shown to contain LHβ(LH cells) were observed. FSH cells became enlarged, while LH cells appeared reduced in size by administration of CPA. In some treated bitches ACTH/MSH cells showed atrophy and regressive changes, whereas TSH cells seemed to become enlarged and were more densely arranged. These structural responses indicate that, in addition to its partial antigonadotropic properties, CPA as a synthetic progesterone derivative may stimulate GH secretion and possibly suppress CRH-ACTH activity in the ovariectomized beagle bitch.
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  • 97
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    Cell & tissue research 183 (1977), S. 319-328 
    ISSN: 1432-0878
    Keywords: Hypothalamus ; Human fetus ; Somatostatin ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Immunocytochemical techniques have enabled us to characterize the hypothalamic somatostatin system in the human fetus and to study its ontogenesis. Somatostatin-containing neurons appear as early as the 16th week of fetal life. Their perikarya belong to two distinct cell populations: some of them, of large size, form clusters in the magno-cellular nuclei (S.O.N.-P.V.N.); they seem to be neurophysin-positive. The others, parvo-cellular, lie scattered in ventral periventricular areas; they are neurophysin-negative. Most of the immunoreactive fibers pass through the M.E. and terminate in two distinct territories: on the one hand close to the vessels of the primary portal plexus (these territories being neurophysin-negative) and on the other hand, in the peripheral regions of the neural lobe (these territories being neurophysin-positive). The staining reactions obtained with the anti-somatostatin and anti-neurophysin I.S. suggest the existence of 2 hypothalamic somatostatin systems. The former (neurophysin-negative) which appears to originate from the parvocellular perikarya and which terminates in the M.E., controlling adenohypophyseal cells, the latter (neurophysin-positive) originating from one of the S.O.N. and P.V.N. cell populations appears to terminate in the neural lobe. The existence of the latter system suggested by the results of the present and the preceding studies on other species has yet to be fully established.
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  • 98
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    Cell & tissue research 183 (1977), S. 167-175 
    ISSN: 1432-0878
    Keywords: Immunocytochemistry ; Gonadotrophic hormones (FSH, LH) ; Pituitary gland ; Dog (Beagle)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Using the immunoperoxidase technique and antisera to the specific beta (β) subunits of FSH and LH1, selective immunochemical staining was localized mostly in the same cell type in the pars distalis and pars tuberalis of the dog pituitary gland. However, some cells were consistently shown to react solely with antisera to either LHβ or FSHβ. The cells stained for FSHβ were at least 1.5 times less numerous than those shown to contain LHβ. In the pars distalis of adult male dogs the immunoreactive gonadotrophs varied greatly in their relative proportion and were mostly shown to be much less numerous than in bitches in the anestrus phase of the sexual cycle. These cells were found to be positive to aldehyde fuchsin, alcian blue, periodic acid-Schiff (PAS) and aniline blue. The performic acid-alcian blue (pH 0.2)-PAS-orange G procedure stained the FSH/LH cells blue or turquoise, demonstrating TSH cells (blue-purple), ACTH/MSH cells (red-purple) and PRL cells (orange-red). The FSH/LH cells were further differentiated from other functional cell types of the pars distalis on the basis of their typical cytological features, intraglandular distribution and by immunochemical double staining. These observations support the concept that the one cell-one hormone theory may not apply to gonadotrophic hormones, although some cells seem to be the source of either FSH or LH.
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  • 99
    ISSN: 1432-0878
    Keywords: Mammalian secretin cell ; Distribution ; Ontogeny ; Ultrastructure ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Immunocytochemically, secretin cells have been demonstrated to occur in the duodenum and jejunum of several mammals. Calculations on the relative frequency of such cells indicate that the bulk of secretin occurs in the jejunum, a fact supporting the view that secretin may be released by physiological stimulants other than hydrochloric acid. Electron microscopical identification of cat and pig secretin cells confirmed their identity with the ultrastructurally defined S cells, and staining experiments revealed that secretin cells were argyrophilic both with the method of Grimelius and with that of Hellerström and Hellman. Secretin cells are detected already in the 17-day old fetal rat duodenum and show a developmental pattern similar to that displayed by the gastrin cells. It is suggested that secretin may play a role in the early regulation of growth of the fetal gastrointestinal tract.
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  • 100
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    Cell & tissue research 179 (1977), S. 467-473 
    ISSN: 1432-0878
    Keywords: Neurophysin ; Supraoptic nucleus ; Neurosecretory granules ; Electron microscopy ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Localization of neurophysin in neurons of the supraoptic nucleus was accomplished using an unlabeled-antibody, post-embedding, immunoperoxidase technique. Neurophysin was exclusively associated with neurosecretory granules within cell bodies of supraoptic neurons and their processes.
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