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  • Rat  (7)
  • phenobarbital
  • Springer  (13)
  • Annual Reviews
  • National Academy of Sciences
  • Springer Science + Business Media
  • 1980-1984  (13)
  • 1983  (4)
  • 1980  (9)
Collection
Publisher
  • Springer  (13)
  • Annual Reviews
  • National Academy of Sciences
  • Springer Science + Business Media
Years
  • 1980-1984  (13)
Year
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 17 (1980), S. 197-202 
    ISSN: 1432-1041
    Keywords: hexobarbital ; cholestasis ; phenobarbital ; rifampicin ; phenytonin ; pharmackoinetics ; drug metabolism ; induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of intravenously infused hexobarbital was studied in 10 patients with intrahepatic cholestasis and in 9 with extrahepatic biliary obstruction. The results were compared with those obtained in 16 healthy young volunteers and 5 older patients with normal liver function. After infusion, the plasma concentrations showed a rapid initial decline (α-phase) and subsequently a slower decrease (β-phase). The half-life of a latter phase was 323±84 min in the healthy group, 357±151 min in the patients with intrahepatic cholestasis and 344±115 min in the group with biliary obstruction; the clearances were 3.41±0.90, 4.08±1.95 and 3.81±1.97 ml×min−1×kg−1, respectively. The differences were not statistically significant. The mean volume of the central compartment of distribution and the steady state volume of distribution were not significantly different. In two patients hexobarbital clearance during cholestasis was greater than after it had subsided. After treatment of 11 patients with cholestasis with drug metabolism-inducing agents (phenobarbital, rifampicin or phenytoin), the half-life of hexobarbital was significantly shortened and the mean value of hexobarbital clearance was more than doubled.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: primidone ; phenobarbital ; placental transfer ; PEMA ; neonatal metabolism ; aminopyrine demethylation ; renal clearance ; breast milk ; withdrawal symptoms ; GC-MS analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The placental transfer of primidone and its metabolites phenobarbital, phenylethylmalondiamide (PEMA) and p-hydroxyphenobarbital (free and conjugated) has been investigated at birth in 14 epileptic women who had been treated with primidone throughout pregnancy. All drugs studied were found in similar concentrations in maternal and cord blood. In seven of the newborns the pharmacokinetics of these drugs were studied during the first postnatal weeks. Primidone and phenobarbital were eliminated with mean half-lives of 23±10 h and 113±40 h, respectively, PEMA with 35±6 h. In some neonates the serum concentrations of phenobarbital and PEMA increased during the first few days due to their formation by neonatal primidone metabolism. Some babies showed a biphasic elimination pattern with elimination rates increasing after a few days. Although half-lives varied greatly, they corresponded well with renal clearance values and aminopyrine demethylase activities as measured by13CO2-exhalation from13C-labelled aminopyrine. Two newborns whose mothers had been treated with phenytoin in addition to primidone, showed half-lives, renal clearance values and aminopyrine demethylase activities well within the corresponding ranges for adults, thus demonstrating prenatal induction. Newborns whose mothers had been treated with valproate as comedication, did not exhibit elevated excretion rates as compared to newborns of mothers who were treated with primidone alone. Withdrawal symptoms developed in two newborns at times when primidone had been essentially excreted, and in spite of the presence of elevated phenobarbital and PEMA levels. All drugs studied were also present in mothers' milk. During breast feeding, drugs ingested with the milk contributed to the neonate's blood levels, particularly in the case of phenobarbital.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 18 (1980), S. 255-261 
    ISSN: 1432-1041
    Keywords: D-glucaric acid ; renal insufficiency ; phenobarbital ; dipyrone ; cortisol ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The urinary excretion rate ofD-glucaric acid, an in vivo parameter of the activity of drug metabolizing enzymes, has been determined in patients with chronic renal insufficiency (glomerular filtration rate 4.5–80 ml/min/1.73 m2). The mean value of 22.3 µmoles/d (SD 7.2; n 28) was almost identical to that of healthy controls (22.1 µmoles/d, SD 7.3; n 22). Thus, no inhibitory or enhancing effect of renal insufficiency could be detected. The ability of this parameter to indicate alterations in the activity of hepatic drug metabolism, even in patients with renal insufficiency, was demonstrated by the increased excretion rate of glucaric acid (107 µmoles/d, SD 43.5; n 8; p〈0.001) after treatment for 7 days with the enzyme inducer phenobarbital. No significant correlation was found between glucaric acid excretion and sex, age, body weight or body surface in 50 patients. Glucaric acid excretion, therefore, should not be related to the creatinine content of urine samples, since creatinine excretion decreases with severity of renal insufficiency and varies with sex, age, body weight and many other conditions. A single dose of dipyrone (Novalgin®), a further in vivo indicator of drug metabolism, increased glucaric acid excretion on the same day, but no interference was found after a single dose of cortisol.
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  • 4
    ISSN: 1432-1041
    Keywords: guanfacine ; hypertension ; phenobarbital ; withdrawal syndrome ; enzyme induction ; pharmacokinetics ; renal insufficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The unusual observation of a withdrawal syndrome due to guanfacine in a hypertensive patient with chronic renal failure led to a study of the kinetics of the drug in this patient. The principal pharmacokinetic parameters of guanfacine were greatly altered, with extended biotransformation and a decrease in the half-life compared to the values observed in other cases of severe renal insufficiency. Associated treatment with phenobarbital had had a considerable effect, as shown by the results of a further kinetic study 2 months after withdrawal of the phenobarbital. The findings then were in good agreement with reference values which strongly suggests a consequence of the enzyme inducing effect of phenobarbital. Advice about the dosage regimen in such cases is given.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 18 (1980), S. 95-104 
    ISSN: 1432-1041
    Keywords: corticosteroids ; progestins ; betamethasone ; phenobarbital ; amniotic fluid ; fetoplacental unit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Corticosteroids (CS) are known to be essential for fetal organ maturation and seem to play an important role in both the initiation of parturition and the postnatal adaptation of the human neonate. Pharmacologically, CS are widely used for enhancing fetal lung maturation prior to premature delivery. However, knowledge of endogenous CS and precursor levels throughout fetal and perinatal life and their response to exogenous CS is limited. Therefore, using automated liquid column chromatography plus specific radioimmunoassays, unconjugated aldosterone (Aldo), corticosterone (B), 11-deoxycorticosterone (DOC), progesterone (P), 17-hydroxyprogesterone (17-OHP), 11-deoxycortisol (S), cortisol (F) and cortisone (E) were simultaneously followed in 70 amniotic fluid (AF) control samples throughout pregnancy, and in cord and neonatal plasma longitudinally during the first week of life. From 14 to 38 weeks, AF levels of all measured steroids except E rose by 2 to 12-fold on the average (allP〈0.001) but declined at term. E increased until 31–35 weeks (P〈0.01), then remained almost constant until term. Cord levels of all steroids were substantially higher than those found in AF at term. While levels of the placentally derived steroids P, 17-OHP, DOC and E dropped sharply after birth by several orders of magnitude (P≪0.01) showing typical disappearance curves, the biologically most potent CS Aldo and F rose even further immediately after birth. Whereas Aldo levels declined from maxima about 100 times above normal adult levels at 6 h by almost 3-fold until day 7 (P〈0.01), F (and also B) fluctuated considerably resembling a damped oscillation and, by day 7, reached mean levels less than half of those seen in later childhood. After betamethasone treatment of the mother, neonatal levels of Aldo and F were suppressed to 24–69% of normal until day 9, whereas those of the other steroids (except E) returned to normal during the first hours of life. Phenobarbital (PB) therapy of the mother led to decreased steroid levels in maternal and umbilical venous plasma at term, while umbilical arterial CS levels, notably those of Aldo and F (P〈0.02), were increased when compared with untreated controls, indicating a stimulation of the most potent CS in the fetus after PB. The significance of the findings in view of fetoplacental function and fetal organ maturation is briefly discussed.
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  • 6
    ISSN: 1432-0878
    Keywords: Rat ; Preovulatory follicle ; Ultrastructure ; Degeneration ; Atresia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary To identify and describe ovarian follicles committed to undergo follicular degeneration (atresia), immature rats were primed with pregnant mare serum gonadotropin (PMSG). After PMSG treatment, preovulatory follicles develop but subsequently degenerate. Prior to the appearance of pyknotic nuclei (Stage I of atresia), degenerative changes were observed in focal areas of the granulosa cell layer. These changes include “blebbing” of the cytoplasm and alterations in the shape of the granulosa cells. The appearance of these degenerative changes coincides with a decrease in ovarian concentrations of estradiol and testosterone. Since estrogens and androgens maintain the follicle, the decline in estradiol and testosterone could be responsible for the further degenerative alterations that lead to complete deterioration of the preovulatory follicle. In Stage I atretic follicles, lysosome-derived autophagic vacuoles develop and macrophages invade both the thecal and granulosa cell layers. The combined actions of the autophagic vacuoles and macrophages could destroy both the granulosa-cell and thecal layers and thereby transform the preovulatory follicle into an ovarian cyst.
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  • 7
    ISSN: 1432-0878
    Keywords: Juxtaglomerular apparatus ; Sympathetic innervation ; Renin-angiotensin system ; Electron microscopy ; Fluorescence microscopy ; Tupaia belangeri ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary It has previously been reported that the primitive primate Tupaia belangeri develops a renal failure when exposed to psychosocial stress. In order to learn if this high susceptibility to stress of the Tupaia kidney can be correlated with morphological and functional parameters of the Juxtaglomerular apparatus (JGA) and the renin-angiotensin system, comparative experiments were performed on Tupaia and rat. Our results reveal an outstandingly high potency of the JGA and the renin-angiotensin system in Tupaia as evident from the following findings: The Tupaia JGA contains a great number of epithelioid cells abounding in renin granules (electron microscopy). The renin content of the Tupaia kidney is considerably higher than in the rat (radio-immunoassay). The sympathetic innervation of the kidney and especially of the JGA is abundant in Tupaia (fluorescence and electron microscopy). Catecholamine contents of the kidney and other organs are significantly higher in Tupaia than in rats (spectrophotofluorometry). Our results support the previously developed concept of a potent intrarenal neuroendocrine interaction at the JGA level favouring, under certain conditions of social stress, the development of acute renal failure in Tupaia belangeri.
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  • 8
    ISSN: 1432-0878
    Keywords: Splenic implants ; Immunoperoxidase technique ; Lymphocyte homing ; Interdigitating cells ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The localization of T-and B lymphocytes and interdigitating cells (IDC) was investigated during the regeneration process of splenic implants. For this purpose a two-step immunoperoxidase technique was used to visualize T-cell antigen, immunoglobulins and Ia-antigen on cryostat sections. The specific localization of the repopulating lymphocytes occurred simultaneously with the development of non-lymphoid elements characteristic for the different compartments of the white pulp, i.e., the periarteriolar lymphocyte sheaths (PALS) and follicles. The marginal zone (MZ) developed after the PALS and primary follicles, but before germinal center reactions were found. During ontogeny, however, the development of a broad MZ precedes the formation of follicles. This difference in sequence of events is discussed.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 228 (1983), S. 451-457 
    ISSN: 1432-0878
    Keywords: Bone matrix vesicles ; Parathyroid hormone ; Mineralization ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The enzymatic activity of bone matrix vesicles from parathyroidectomized rats was determined and compared to the activity of vesicles from sham operated and normal animals. The vesicles were isolated from the alveolar bone by collagenase digestion and differential centrifugation and further purified on a discontinuous sucrose density gradient. The amount of extractable protein and the activity of alkaline phosphatase, acid phosphatase, and ATPase in the vesicle fractions thus obtained did not differ significantly from the values characteristic of preparations from control rats. It may therefore be suggested that parathyroid hormone depletion and the associated hypocalcemia have no significant effect on the occurrence and phosphatase activity of bone matrix vesicles.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 230 (1983), S. 367-375 
    ISSN: 1432-0878
    Keywords: Rat ; Testis ; Protein ; Endocytosis ; Microperfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary As luminal fluid moves from the seminiferous tubule and enters the rete testis, its protein concentration declines from approximately 6 mg/ml to 1 mg/ml. It was therefore suggested that protein is either 1) utilized by the spermatozoa, 2) transported across the epithelium of the terminal segment of the seminiferous tubule, the tubuli recti or rete testis, or 3) absorbed and degraded by the epithelium. Horseradish peroxidase (HRP), a protein marker, was microperfused into single seminiferous tubules or perfused directly into the rete. After fixation, the HRP was localized histochemically and the tissue observed under the light- and electron microscope. HRP was taken up via pinocytotic vesicles into the cytoplasm of the Sertoli cells and germ cells but did not permeate extracellularly beyond the tight junctions. Similar results were obtained in the cells lining the terminal segment and the tubuli recti. The rete epithelium showed uptake of HRP into coated and noncoated vesicles, while some cells additionally revealed diffuse cytoplasmic distribution of HRP. The terminal segment, tubuli recti, and rete testis may be important routes by which proteins may leave the testicular fluid either to be degraded or to enter the blood.
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