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  • 1980-1984  (2.419)
  • Engineering  (1.378)
  • Rat  (616)
  • pharmacokinetics  (424)
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  • 101
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 85-89 
    ISSN: 1432-1041
    Schlagwort(e): digitoxin ; radioimmunoassay ; pharmacokinetics ; bioavailability ; digitoxin metabolites
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and bioavailability of digitoxin were examined in six normal human subjects using an assay that separates digitoxin from its metabolites. After intravenous administration, the mean systemic clearance was 2.44 ml/min; the volume of distribution was 0.47 l/kg; and the elimination half-life was 6.5 days. After oral administration, the elimination half-life was 5.8 days. The bioavailability was 81.5% using the specific assay. Using a non-specific, direct serum digitoxin radioimmunoassay the bioavailability was 98.0%. Assay of aqueous fractions from extracted serum samples indicated higher levels of water-soluble metabolites following oral compared to intravenous digitoxin administration. These findings suggest that previously reported values for digitoxin bioavailability using non-specific methods may be falsely elevated due to the presence of digitoxin metabolites in serum.
    Materialart: Digitale Medien
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  • 102
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 291-296 
    ISSN: 1432-1041
    Schlagwort(e): naproxen ; cirrhosis ; pharmacokinetics ; protein binding ; nonsteroidal antiinflammatory drugs
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Chronic liver disease is known to alter the absorption and disposition of many drugs. To assess the influence of chronic alcoholic liver disease on the disposition of naproxen, we administered the drug both as a single dose and to steady state to 10 individuals with alcoholic cirrhosis and to 10 healthy controls. Plasma and serum samples collected after naproxen dosing were assayed for both total and (following equilibrium dialysis) unbound drug concentration. Clearance calculated based on both total and unbound naproxen concentration revealed no change in total plasma clearance of the drug at steady state but a marked reduction of approximately 60% in clearance based on unbound drug. Naproxen volume of distribution changed only minimally. Because clearance based on unbound drug concentration at a given dosing rate determines the plasma or blood free drug concentration, this concentration may increase significantly in patients with alcoholic liver disease given usual doses of naproxen. Unbound drug concentration is thought to determine the pharmacologic effect of a drug. We therefore recommend that naproxen dosing be reduced by at least half in patients with chronic alcoholic liver disease. In the absence of data to the contrary, this recommendation can be extended to individuals with other forms of hepatic disease.
    Materialart: Digitale Medien
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  • 103
    ISSN: 1432-1041
    Schlagwort(e): enprofylline ; healthy subjects ; absorption ; pharmacokinetics ; oral- ; duodenal- ; colonic administration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Enprofylline, a new potent bronchodilator xanthine drug, was given orally as an aqueous solution to 6 healthy subjects in single doses of 2, 4 and 6 mg/kg. The two lower doses produced plasma concentrations in the range 1–4 mg/l, i.e. in the assumed “therapeutic interval” according to previous animal studies. A high 24 h urine recovery of unchanged drug, with mean values for the three dose levels ranging from 85 to 91% of the given dose, indicated good absorption and little metabolism. The dose-corrected area under the plasma concentration-time curve rose with dose as the latter was increased from 2 to 6 mg/kg. This indicates that the elimination of enprofylline is capacity-limited at high doses. Double peaks in the plasma concentration-time curves at the higher dose levels suggested intermittent and delayed gastric emptying as a possible explanation. This hypothesis was confirmed by studies in 6 other healthy subjects, who received the drug solution by three different routes; by mouth, via a catheter in the duodenum, and rectally via a catheter in the colon. The corresponding time to peak values (mean±SEM) were 32.5±8.7, 13.3±2.5, and 157±23 min.
    Materialart: Digitale Medien
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  • 104
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 349-354 
    ISSN: 1432-1041
    Schlagwort(e): tolfenamic acid ; anti-inflammatory agents ; biliary excretion ; pharmacokinetics ; intravenous administration ; bile duct cannulation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary To study its pharmacokinetics and especially its biliary excretion, 14C-tolfenamic acid 9.84 µCi/100 mg was infused i.v. in 8 patients with a T-tube inserted in the common bile duct at choledocholithotomy 7–10 days prior to the study. Bile was collected in fractions by continuous suction over a 24 h period. Blood samples were taken and urine collected up to 48 h after the dose. Tolfenamic acid and its metabolites were separated by TLC and were quantitated by liquid scintillation counting. The pharmacokinetics of tolfenamic acid could be described by a two compartment open model with V1 of 3.67±0.68 l and Vss of 8.0±1.0 l. The total plasma clearance of tolfenamic acid averaged 106±8 ml/min and t1/2β was 1.38±0.32 h. A three compartment open model was required to describe the kinetics of total 14C. The plasma clearance of total 14C was 15.4±3.9 ml/min and its terminal half life averaged 19.0±4.1 h. The long half-life was caused by the slow elimination of tolfenamic acid metabolites. Four metabolites were measured in plasma and bile. The principal metabolites in bile were glucuronide/sulphate conjugates of hydroxylated derivatives of tolfenamic acid. The recovery of tolfenamic acid in bile was 1.1±0.3% of the dose, whereas the recovery of total 14C was 18.6±4.9%. The biliary clearances of tolfenamic acid and total 14C were 1.2±0.3 and 5.0±2.1 ml/min, respectively. Thus, biliary excretion plays a considerable part in the pharmacokinetics of tolfenamic acid.
    Materialart: Digitale Medien
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  • 105
    ISSN: 1432-1041
    Schlagwort(e): kelfiprim ; trimethoprim combination ; sulfamethopyrazine combination ; pharmacokinetics ; renal insufficiency
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The combination of trimethoprim (TMP) and sulfamethopyrazine (SMP) has been successfully used to treat chronic urinary tract infections. Since parenchymal involvement associated with renal insufficiency of varying degree is not infrequent in these patients, it was considered important to study the pharmacokinetics of TMP and SMP in a fixed dose combination. Four groups of patients were studied: 1) 4 patients with endogenous creatinine clearance (CLcR) between 80 and 40 ml/min; 2) 3 patients with CLcR between 40 and 10 ml/min; 3) 3 patients on chronic peritoneal dialysis (CAPD); and 4) 3 patients on haemodialysis. A single oral dose of 250 mg TMP and 200 mg SMP was given to each patient. Multiple samples were collected over 9 days and the following pharmacokinetic parameters were calculated: total area under the plasma level curve, slow disposition rate constant β and the corresponding t1/2β, plasma clearance and the apparent volume of distribution. The results show that the two moieties of the TMP-SMP combination behaved differently in uraemic patients as fas as elimination rate was concerned. TMP was eliminated more slowly both in patients with diminished renal function and in those subjected to haemo- or peritoneal dialysis. The reduction in the rate of elimination of TMP was significantly correlated with the degree of renal impairment. The elimination of SMP, however, was not significantly affected by the reduced renal function; indeed a tendency to increase was noted, at least in dialyzed patients. However, as in patients with mild renal insufficiency (CLcR〉40 ml/min) no substantial change in plasma clearance rate need be expected, the TMP-SMP combination could be given to them in the same dose schedule as in people with normal renal function.
    Materialart: Digitale Medien
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  • 106
    ISSN: 1432-1041
    Schlagwort(e): molsidomine ; vasodilators ; pharmacokinetics ; pharmacodynamics ; dose-response relationship ; haemodynamics ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In 12 healthy male volunteers, molsidomine 1, 2 and 4 mg i.v. increased resting heart rate and decreased systolic blood pressure, the latter still being affected after 8 hours. After single oral doses of 1 and 2 mg, systolic pressure tended to be reduced for 90 minutes and exercise heart rate tended to be increased. After oral treatment with 2 mg molsidomine three times daily for 1 week, the pharmacokinetic parameters and the effects on heart rate and blood pressure after the final dose were not different from those after the first dose. The terminal half-life was independent of dose and route of administration. Clearance and distribution volume were not dose-dependent. The bioavailability of a 2 mg oral dose of molsidomine was 44%. Inter-individual variation in heart rate, blood pressure and pharmacokinetics was observed.
    Materialart: Digitale Medien
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  • 107
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 429-433 
    ISSN: 1432-1041
    Schlagwort(e): mepindolol ; renal failure ; haemodialysis ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five patients with a creatinine clearance of 14 to 37 ml/min/1.73 m2 were each given an oral dose of 10 mg of the beta-blocker mepindolol sulphate (Corindolan). In addition, two dialysis patients received the same dose either during hemodialysis or on a dialysis-free day. Plasma levels of mepindolol were measured by a sensitive, specific HPLC method. Mepindolol was rapidly absorbed in all the patients. The maximum plasma level of 35±8 ng/ml was reached after 1.4±0.5 h. The half-life of disposition was 4.0±1.5 h. The area under the plasma concentration-time curve was 237±84 ng × h/ml. The data obtained were no different from those found in normal healthy volunteers.
    Materialart: Digitale Medien
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  • 108
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 471-475 
    ISSN: 1432-1041
    Schlagwort(e): acyclovir ; A515U ; 6-deoxyacyclovir ; pharmacokinetics ; prodrug ; antiviral chemotherapy ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A515U (6-deoxyacyclovir) is an analogue of acyclovir devoid of antiviral activity in vitro but which is well absorbed and undergoes conversion to acyclovir after oral administration to rats. The tolerance and pharmacokinetics of various doses of A515U have been studied in 8 healthy volunteers. Single oral doses of 25, 50, 100, 200 and 400 mg A515U and 400 mg acyclovir for comparison were administered to the volunteers at weekly intervals. Concentrations of the parent drug and acyclovir were determined in plasma and urine. The prodrug was well tolerated and did not cause adverse reactions or changes in haematological or biochemical variables. It was well absorbed and conversion to acyclovir was rapid and extensive at all doses. Plasma concentrations of acyclovir achieved with 50 mg A515U orally were comparable to and less variable than those produced by 400 mg acyclovir. A515U was rapidly cleared with a short plasma elimination half life of approximately 0.5 h. The attainment of high plasma concentrations of acyclovir by oral administration of a prodrug may represent an important advance in antiviral chemotherapy.
    Materialart: Digitale Medien
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  • 109
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 619-621 
    ISSN: 1432-1041
    Schlagwort(e): biperiden ; pharmacokinetics ; pharmacodynamics ; plasma levels
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of biperiden was studied and compared with pharmacodynamics (pupil size, accomodation, self-rating mood scale) in 6 healthy volunteers. A single-blind cross-over design was employed with placebo and biperiden (4 mg as commercially available tablets). After a lag time of 0.5 h, biperiden was rapidly absorbed with a half-life of 0.3 h, plasma peak levels of 5 ng/ml being reached after 1.5 h. Biperiden showed good tissue penetration (distribution half-life 0.6 h; ratio of total to central distribution volume 9.6), the terminal half-life time of plasma concentration was 18 h, and the oral clearance was 146 l/h. The pharmacodynamic maximum lagged behind the plasma peak concentration by 1 (self-rating) to 4 h (accommodation).
    Materialart: Digitale Medien
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  • 110
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 121-124 
    ISSN: 1432-1041
    Schlagwort(e): methotrexate ; psoriasis ; pharmacokinetics ; plasma levels ; urinary excretion ; renal clearance ; tubular absorption
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The plasma concentration and urinary excretion of methotrexate were followed in twelve psoriatic patients after intravenous and oral doses of methotrexate ranging from 7.5 to 30 mg. In six of the patients, a nonlinear relation was found between the fractional amount of methotrexate excreted in the urine and the corresponding area under the plasma concentration-time curve. The methotrexate clearance was found to be increased during the initial high plasma concentration, probably due to saturation of the tubular reabsorption of methotrexate. Considerable interindividual variation was found in the apparent saturation point of the active reabsorption, but up to 500–800 ng/ml first order kinetics still applied. At plasma concentrations below saturation, the renal clearance of methotrexate ranged from 52–102 ml/min (mean±SD, 83±19.4 ml/min).
    Materialart: Digitale Medien
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  • 111
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 87-93 
    ISSN: 1432-1041
    Schlagwort(e): enprofylline ; pharmacokinetics ; renal elimination ; renal insufficiency ; healthy subjects ; creatinine clearance ; side effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Enprofylline, a new bronchodilating drug, was given i.v. at 1.0 mg/kg to 7 healthy subjects and to 14 patients with differing degrees of chronic renal insufficiency. Plasma and urine concentrations of unchanged drug were followed by HPLC. In the patients the plasma half-life was prolonged and the total and renal clearances were reduced in direct proportion to the degree of renal insufficiency as determined by creatinine clearance. The unbound fraction of enprofylline in plasma increased from 55% in the healthy subjects to 66% in the group of patients with the highest degree of renal impairment. The volume of distribution terms, Vβ and Vss, both tended to decrease with decreasing creatinine clearance. When the volume term calculations were based on the unbound drug level in plasma, this tendency was enhanced. Side-effects were noted in 4 subjects, and to some extent were related to the plasma level of the drug.
    Materialart: Digitale Medien
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  • 112
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 113-119 
    ISSN: 1432-1041
    Schlagwort(e): estramustine phosphate ; prostatic cancer ; pharmacokinetics ; metabolism ; estramustine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of estramustine phosphate (EMP) was studied in five prostatic cancer patients given single i.v. and oral doses of EMP in a cross-over study. Plasma and urinary concentrations of parent drug, estramustine, estromustine (the estrone analogue), estradiol and estrone were followed for 32 h. The elimination of intravenous EMP from plasma was biphasic. The mean volumes of distribution were small, being 43 and 108 ml/kg for the central and peripheral compartments, respectively. The plasma clearance was 64 ml/kg/h, and the half-lives of the two phases were 0.16 and 1.27 h. Metabolism was the major route of elimination of EMP. It was readily dephosphorylated and oxidized to yield the cytotoxic metabolites estramustine and estromustine. Estromustine was the main metabolite in plasma. When given orally EMP underwent extensive presystemic dephosphorylation, which started in the gastrointestinal tract. The relative bioavailability of estromustine after administration of EMP-capsules was 44%, which reflects incomplete absorption of EMP rather than first-pass metabolism of estromustine. The terminal half-life of estromustine was 10–20 h, which suggests that EMP might be given once or twice a day.
    Materialart: Digitale Medien
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  • 113
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 341-346 
    ISSN: 1432-1041
    Schlagwort(e): cimetidine ; pharmacokinetics ; critically ill patients ; intravenous administration ; dose individualization
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Cimetidine disposition was studied after rapid (1 min) intravenous infusion in eight critically ill patients aged between 20 years and 77 years; one patient was studied on two occasions. Cimetidine dose was 300 mg in seven patients and 400 mg in the remaining patient. Arterial plasma cimetidine concentrations at the end of the infusion were very high and ranged from approximately 15–35 mg/l. Pharmacokinetic parameters displayed wide interpatient variability (coefficients of variation of 30–50%) and significant relationships emerged between some of these parameters and certain patient characteristics. Most notable, total systemic plasma clearance of cimetidine was directly related to estimated creatinine clearance (p〈0.01). This relationship might prove to be a useful method of individualizing cimetidine dosage in critically ill patients.
    Materialart: Digitale Medien
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  • 114
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 505-511 
    ISSN: 1432-1041
    Schlagwort(e): prednisolone ; prednisone ; oral contraceptives ; 6β-hydroxylase ; transcortin ; protein-binding ; steroid metabolism ; pharmacokinetics ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The oestrogenic component of oral contraceptives affects the activity of liver enzymes and the concentrations of plasma proteins implicated in steroid metabolism and transport. The present study was designed to determine these effects on the kinetics of prednisone and prednisolone. After an oral dose of prednisone, women on oral contraceptive steroids (n=10) had higher mean (±SD) area under the plasma concentration versus time curves of total (428±67 µg/ml/min vs 188±28 µg/ml/min, p〈0.001) and unbound prednisolone (64±10 µg/ml/min vs 41±10 µg/ml/min, p〈0.001) than women not taking oral contraceptive steroids (n=10). The differences were attributable to a lower non-renal clearance of prednisolone and to a higher apparent systemic availability of the drug in contraceptive users than in the controls. The affinity of albumin and transcortin for prednisolone was lower in women on oral contraceptives than in controls (p〈0.001). Thus, altered kinetics and protein binding may account for the known increase in glucocorticoid efficacy by oestrogens.
    Materialart: Digitale Medien
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  • 115
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 591-593 
    ISSN: 1432-1041
    Schlagwort(e): cyclophosphamide ; liver failure ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of cyclophosphamide was investigated in 7 patients in severe liver failure. The pharmacokinetic data were compared with those derived from a matched control group of patients with normal liver function. The half-life (t1/2) of cyclophosphamide following intravenous administration in patients with liver failure was 12.5±1.0 h (m±SD), which was significantly longer than in the normal controls in whom it was 7.6±1.4 h (p〈0.001). The mean total body clearance (Clt) was significantly smaller in liver failure at 44.8+8.6l·kg−1 than in the controls in whom it was 63.0±7.6l·kg−1 (p〈0.01). It is concluded that severe liver disease has a significant effect on the disposition of cyclophosphamide, and that it could lead to accumulation of the drug in the body.
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  • 116
    ISSN: 1432-1041
    Schlagwort(e): cefoperazone ; peritoneal dialysis ; pharmacokinetics ; terminal renal failure ; peritonitis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of cefoperazone after i.p. and/or i.v. administration were studied in 12 CAPD patients. After i.v. injection, the plasma half-life was 2.65±0.4 h, the total clearance amounting to 70.1±19.2 ml/min. Peritoneal clearance was calculated to be 6.9±1 ml/min. After peritoneal instillation, the bioavailability was 63.9±5%. After repeated i.p. administration, no accumulation of the drug in the body was observed. Thus, cefoperazone can be safely administered for the treatment of peritonitis in CAPD patients.
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  • 117
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 651-653 
    ISSN: 1432-1041
    Schlagwort(e): prednisolone ; prednisone treatment ; pharmacokinetics ; individual variation ; microsomal enzyme induction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Eleven patients on long-term prednisone treatment were studied on two occasions separated by 45 to 325 days. In 10 patients the total body clearance of prednisolone only changed about 10%. In one case a 78.5% decrease was observed after stopping treatment with rifampicin and isoniazide. No association was found between the prednisone dose rate (mg/kg per month), patient age or mean endogenous plasma hydrocortisone level and prednisolone clearance/kg. The results indicate considerable intra-individual consistency of prednisolone kinetics if other conditions are not changed.
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  • 118
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 105-110 
    ISSN: 1432-1041
    Schlagwort(e): phenytoin ; epileptic women ; pharmacokinetics ; bioavailability ; pregnancy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five epileptic women needing to commence phenytoin therapy during pregnancy received a single intravenous and a single oral dose of phenytoin several days apart before starting regular intake of the drug. Plasma phenytoin concentration — time data were analysed by three different pharmacokinetic techniques. However assessed, the mean oral bioavailability of the drug proved to be about 90% of the intravenous bioavailability. This finding makes it unlikely that impaired bioavailability accounts for the increase in oral phenytoin dosage necessary in pregnancy to maintain plasma phenytoin concentrations at pre-pregnancy values. Phenytoin clearance in the pregnant subjects was approximately double the published values for phenytoin clearance in nonpregnant persons. This suggests that increased (metabolic) clearance accounts for the increased phenytoin dosage requirement of pregnancy.
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  • 119
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 159-163 
    ISSN: 1432-1041
    Schlagwort(e): endralazine ; renal impairment ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The influence of renal impairment on the pharmacokinetics of endralazine was studied in 12 patients; 4 patients on regular haemodialysis therapy (creatinine clearance less than 5 ml/min) and 8 patients with varying degrees of renal impairment (creatinine clearance 11–52 ml/min). Following an oral dose of 10 mg endralazine the mean terminal elimination half-life (βt1/2) in the dialysis sub-group was prolonged at 7.1 h (range 3.3 to 14 h), compared to 3.6 h in the other renal patients (and compared to 2.3 h in hypertensive patients with normal renal function). After one week's therapy with 10 mg B.D. endralazine in the 8 patients with moderate renal impairment there was a significant increase in βt1/2 to 8.6 h but there was no significant change in the area under the drug concentration-time curve and no evidence of drug accumulation. In this study those patients with the poorest renal function had the longest βt1/2 after acute dosing. There was a significant correlation between creatinine clearance and acute βt1/2 but there was considerable variability in individual patients and, even with severe degrees of renal impairment, major dose adjustments do not appear necessary.
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  • 120
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 217-222 
    ISSN: 1432-1041
    Schlagwort(e): metoprolol ; pharmacokinetics ; age effect ; repeated doses ; pre-systemic elimination ; total body clearance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of long-term treatment on the absorption and dispsoition of metoprolol has been evaluated in 8 healthy, non-smoking, elderly individuals (mean age 74.5 years) and in a control group of 8 healthy, young individuals. Two trace doses of [3H]metoprolol were given i.v., first concomitantly with a single oral 50 mg dose of cold metoprolol, and second, with the morning dose after 2 weeks of treatment with 50 mg b.d. In the elderly, the mean AUC increased by about 45% (p〈0.05) over the treatment period, while in the control group the mean AUC was 18% greater (p〈0.05) on Day 14 than on Day 1. In the elderly, changes both in pre-systemic elimination and in total body clearance accounted for the elevation of the AUC, whereas reduced first-pass effect appeared to be the major cause of the increased steady-state plasma level in the control group. With the exception of the volume term, V β , the pharmacokinetic parameters were not significantly different between the elderly and the young individuals. For this reason, almost identical steady-state plasma levels were attained in the two groups. The results suggest that age-related physiological changes may have some minor effects on the pharmacokinetics of metoprolol, and also that the changes do not lead to significantly altered plasma concentrations compared to those in young individuals.
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  • 121
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 335-339 
    ISSN: 1432-1041
    Schlagwort(e): transdihydrolisuride ; dopamine agonist ; pharmacokinetics ; pharmacodynamics ; prolactin levels ; side-effects ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma levels and urinary excretion of the dopamine agonist, transdihydrolisuride (TDHL), were measured by radioimmunoassay in healthy male volunteers given TDHL 50 µg i.v. and oral doses of 200, 400 and 800 µg. Plasma prolactin was also measured by radioimmunoassay. Following i.v. injection, the concentration of TDHL declined with a half-life of 37±19 min. The total clearance was 38±27 ml/min/kg and the apparent volume of distribution was 1.3±0.4 l/kg. The bioavailability of oral TDHL was proportional to the dose; after 200, 400 and 800 µg the bioavailability was 20±25%, 31±24% and 48±26%. TDHL was almost totally metabolized and less than 0.5% of the dose was excreted unchanged in urine in 24 h. Plasma prolactin levels were depressed by 66±15%, 75±11% and 80±7% after TDHL 200 µg, 400 µg and 800 µg. The effect lasted for more than 12 h after the lowest dose and for more than 24 h after 400 and 800 µg. Side effects, mainly nausea and headache, only occurred at the two highest dose levels.
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  • 122
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 583-587 
    ISSN: 1432-1041
    Schlagwort(e): propranolol ; pregnancy ; beta-adrenoceptor antagonist ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Propranolol, a beta-adrenoceptor blocking drug, was administered to 6 healthy pregnant volunteers between 32 and 36 weeks gestation and when at least 6 weeks postparum. On both occasions, subjects were given propranolol 120 mg orally or 10 mg intravenously in randomised order with a minimum washout period of 1 week. Propranolol was assayed in plasma by gas-liquid chromatography with electron-capture detection and the pharmacokinetic parameters were investigated. There were no significant alterations in elimination half-life, clearance or apparent volume of distribution per kilogram antenatally compared with postnatally: bioavailability was also unchanged. It is concluded that the disposition of propranolol is not altered during pregnancy.
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  • 123
    ISSN: 1432-1041
    Schlagwort(e): Bezitramide ; oral absorption profile ; pharmacokinetics ; male volunteers ; experimental pain ; biliary excretion in rats
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The oral absorption of bezitramide 5 mg was studied in 7 human volunteers, using a specific radioimmuno-assay which measured both bezitramide and its active metabolite R-4618. A lag time of 0.5–1.0 h and a Cmax of 5.4 ng/ml plasma were found, the latter occurring 2.5–3.5 h after administration. The apparent elimination half-life varied from 11 to 24 h. Less than 0.3% of the dose was excreted unchanged in the urine. High concentrations in the faeces of some individuals indicate incomplete absorption and/or biliary secretion. The analgesic effect, using a standardized superficial electrical stimulation method, reached its maximum between 2.5 and 3.5 h after dosing, in accordance with the absorption phase. The duration of the effect was highly variable. Experiments in rats (n=6,3H-bezitramide 2.5 µg), demonstrated extensive biliary excretion (up to 70% of total radioactivity) and less than 3% of the label was removed by urinary excretion.
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  • 124
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 129-131 
    ISSN: 1432-1041
    Schlagwort(e): aprindine ; antiarrhythmic agent ; healthy volunteers ; plasma level ; oral administration ; pharmacokinetics ; urinary excretion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The disposition of aprindine following a single oral dose can best be described by a two-compartment open model. The mean plasma half-life (t1/2β) increased from 8.0±2.1 h (SD) after a 25 mg dose to 9.4±2.9 h after 50 mg and to 15.8±2.6 h after 100 mg, with a decrease in total plasma clearance (Cl/F) and volume of distribution at steady state (Vdss/F) and during β-phase (Vdβ/F). The area under plasma concentration-time curve (AUC), maximum plasma concentration (Cmax) and the amount of unchanged aprindine excreted in the urine increased in a non-linear fashion with the increase in dose. The t1/2β after multiple oral doses showed a 3-fold increase over the single dose value. These results indicate that aprindine shows dose-dependent non-linear kinetics.
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  • 125
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 191-195 
    ISSN: 1432-1041
    Schlagwort(e): furosemide ; triamterene ; drug combination ; pharmacodynamics ; pharmacokinetics ; furosemide retard ; triamterene metabolite ; urine potassium
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacodynamics and pharmacokinetics of the combination of furosemide retard (30 mg)/triamterene (50 mg) were compared with furosemide (30 mg) in 18 healthy male volunteers aged 39.3±6.3 years. After the administration of furosemide the onset of its effect was very rapid, reaching a maximum between 1.5 to 3 h, and followed by rebound after 9 to 10.5 h. In contrast the combination furosemide retard/triamterene showed a protracted course with a duration of effect up to 12 h. The general effect over 12 h of the two preparations was equivalent with respect to the excretion of urine, sodium, chloride and calcium, but the combination caused significantly less excretion of potassium (p≤0.05) than furosemide. After a lag-phase of 33.9±5.4 min the maximum plasma concentration of furosemide was reached after 3.47±0.66 h, and the elimination half-life was approximately 2 h. After a lag-phase of 33.0±17.8 min the maximum plasma concentration of the main metabolite of triamterene, the OH-TA sulphuric acid ester, was reached after 1.7±0.59 h, and its elimination half-life amounted to 1.25±0.37 h. Because of the sustained release of furosemide from the retard-formulation, its principal pharmacokinetic parameters were better adapted to those of triamterene. The consequences were not only a protracted effect but also an improved electrolyte profile, especially with regard to reduced loss of potassium. In the case of renal insufficiency, however, the potassium level in serum might be increased to an undesirable extent.
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  • 126
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 269-270 
    ISSN: 1432-1041
    Schlagwort(e): cyclophosphamide ; cytostatic drug ; cancer therapy ; female breast cancer ; bioavailability ; rapid release formulations ; gastric juice resistant formulation ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Cyclophosphamide (CP) is an alkylating cytostatic compound, which is activated to its cytotoxic form in the liver [1]. Since the therapeutic range of CP in the treatment of human tumours, is small like other cytostatics, a constant high bioavailability is essential for its oral administration. Although CP has become one of the most widely used cytostatics [2], there do not appear to have been any bioavailability investigations providing the necessary information. The development of a very sensitive gas chromatographic analytical method has now permited investigation of the pharmacokinetics of oral CP in conventional clinical doses [3, 4, 5, 6].
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  • 127
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 485-489 
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; erythromycin ; interaction ; metabolism ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In 11 healthy volunteers the kinetics of theophylline and the plasma levels and the urinary excretion of its metabolites were studied before and after treatment with erythromycin for 10 days. Theophylline was administered as an intravenous bolus injection (280 mg) followed by a constant intravenous infusion (23.8±4.1 mg/h) for 6 hours. The total clearance of theophylline at steady-state (63.4±9.9 vs 63.8±14.4 ml/min, before vs after erythromycin treatment) and the elimination half-life after cessation of the infusion (6.7±2.6 vs 7.5±1.8 h, before vs after treatment) did not change during the treatment with erythromycin. No difference in the formation of metabolites before and after treatment with erythromycin was detected; the findings in urine were 40.4±5.0 vs 42.1±5.4% 1,3-dimethyluric acid, 29.6±4.6 vs 30.1±5.9% 1-methyluric acid and 13.4±3.5 vs 12.5±2.2% 3-methylxanthine before and after erythromycin treatment, respectively. It is concluded that a clinically relevant interaction between erythromycin and theophylline does not occur.
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  • 128
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 603-608 
    ISSN: 1432-1041
    Schlagwort(e): pinacidil ; hypertension ; pinacidil pyridine-N-oxide ; urinary excretion ; protein binding ; pharmacokinetics ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Preliminary investigation in 3 healthy volunteers suggested that intravenous pinacidil in a dose of 0.2 mg/kg had a potent but well-tolerated hypotensive action in the supine position. Facial flushing, uncomfortable chest sensation and distressing postural hypotension occurred at serum concentrations above 300 ng/ml. Pinacidil, 0.2 mg/kg, was given intravenously over 4 min to 15 healthy volunteers in the supine position. Maximum fall in mean arterial pressure (MAP) was 15.7±6.0 mmHg. Maximum rise in heart rate was 23.8±6.6 beats/min. Pinacidil serum distribution half-life ( $${\text{T}}_{{\raise0.7ex\hbox{${\text{1}}$} \!\mathord{\left/ {\vphantom {{\text{1}} {{\text{2}}\alpha }}}\right.\kern-\nulldelimiterspace}\!\lower0.7ex\hbox{${{\text{2}}\alpha }$}}}$$ ) was 13.4±8.5 min and elimination half-life ( $${\text{T}}_{{\raise0.7ex\hbox{${\text{1}}$} \!\mathord{\left/ {\vphantom {{\text{1}} {{\text{2}}\beta }}}\right.\kern-\nulldelimiterspace}\!\lower0.7ex\hbox{${{\text{2}}\beta }$}}}$$ ) was 2.13±0.49 h. The apparent volume of distribution (Vdβ) was 90.3±13.21 and total body clearance was 31.1±9.61/h. Pinacidil was approximately 40% bound to plasma protein over the concentration range 40–400 ng/ml. Urinary excretion of unchanged pinacidil accounted for 5.7 ± 1.3% of the administered dose over 24 hours and urinary excretion of the major metabolite, pinacidil pyridine-N-oxide, was 31.6±9.2% of the administered dose. It was concluded that intravenous pinacidil is a potent vasodilator hypotensive compound, with a duration of action between 1.5 and 2 h.
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  • 129
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 111-114 
    ISSN: 1432-1041
    Schlagwort(e): chlorambucil ; chronic lymphocytic leukaemia ; phenylacetic acid mustard ; food intake ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The influence of food intake on the pharmacokinetics of chlorambucil (C) and its cytotoxic metabolite, phenylacetic acid mustard (PAM), has been studied in man after oral doses of chlorambucil. The administration of chlorambucil with food resulted in slower absorption than when fasting. However, the area under the plasma concentration-time curve (AUC) was unaffected. The mean ratio AUCPAM/AUCC was 2.8 (range 1.4–7.1) under fasting and 3.3 (range 1.3–7.4) under nonfasting conditions. The metabolite very probably plays an important role in the cytotoxic effects observed after administration of C, since calculations show that a major fraction of the metabolite is eliminated by alkylation reactions.
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  • 130
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 115-117 
    ISSN: 1432-1041
    Schlagwort(e): benzodiazepine antagonist ; Ro 15-1788 ; healthy volunteers ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of the selective benzodiazepine antagonist Ro 15-1788 has been studied in 6 healthy male volunteers following a single intravenous dose of 2.5 mg. The drug was only slightly bound to plasma proteins (40±8%, mean±SD). A negligible amount (〈0.2% of the dose) of unchanged drug was recovered in urine. Hepatic elimination was rapid, as shown by a short t1/2 of 0.9±0.2 h, and high total plasma and blood clearances of 691±216 ml/min and 716±199 ml/min, respectively. The fast decline of plasma levels from about 60 to 2 ng/ml accounts for the short-lasting reversal of benzodiazepine-induced sedation by Ro 15-1788.
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  • 131
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 85-89 
    ISSN: 1432-1041
    Schlagwort(e): digitoxin ; radioimmunoassay ; pharmacokinetics ; bioavailability ; digitoxin metabolites
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and bioavailability of digitoxin were examined in six normal human subjects using an assay that separates digitoxin from its metabolites. After intravenous administration, the mean systemic clearance was 2.44 ml/min; the volume of distribution was 0.47 l/kg; and the elimination half-life was 6.5 days. After oral administration, the elimination half-life was 5.8 days. The bioavailability was 81.5% using the specific assay. Using a non-specific, direct serum digitoxin radioimmunoassay the bioavailability was 98.0%. Assay of aqueous fractions from extracted serum samples indicated higher levels of water-soluble metabolites following oral compared to intravenous digitoxin administration. These findings suggest that previously reported values for digitoxin bioavailability using non-specific methods may be falsely elevated due to the presence of digitoxin metabolites in serum.
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  • 132
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 119-121 
    ISSN: 1432-1041
    Schlagwort(e): S-adenosyl-L-methionine ; pharmacokinetics ; protein binding ; dose-dependent kinetics ; healthy volunteers ; urinary excretion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary S-Adenosyl-L-methionine (AdoMet) kinetics was studied in 6 male subjects given 100 and 500 mg i. v. Drug concentrations in plasma and urine were assayed using a radioenzymatic method. Pharmacokinetic parameters were estimated according to an open two-compartment model. The apparent volumes of distribution after the 100 and 500 mg doses were 407±27 and 443±36 ml/kg (mean±SEM), terminal half-lives 81±8 and 101±7 min and body clearances 3.7±0.5 and 3.1±0.2 ml/min per kg. Urinary excretion was 34±3 and 40±2% of the administered dose. The results demonstrate that drug disposition occurs more via metabolism than via renal excretion, and it is not dependent on the administered dose. Binding of AdoMet to serum proteins is negligible.
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  • 133
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 115-117 
    ISSN: 1432-1041
    Schlagwort(e): benzodiazepine antagonist ; Ro 15-1788 ; healthy volunteers ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of the selective benzodiazepine antagonist Ro 15-1788 has been studied in 6 healthy male volunteers following a single intravenous dose of 2.5 mg. The drug was only slightly bound to plasma proteins (40±8%, mean±SD). A negligible amount (〈0.2% of the dose) of unchanged drug was recovered in urine. Hepatic elimination was rapid, as shown by a short t1/2 of 0.9±0.2 h, and high total plasma and blood clearances of 691±216 ml/min and 716±199 ml/min, respectively. The fast decline of plasma levels from about 60 to 2 ng/ml accounts for the short-lasting reversal of benzodiazepine-induced sedation by Ro 15-1788.
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  • 134
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 243-245 
    ISSN: 1432-1041
    Schlagwort(e): mebendazole ; haemodialysis ; echinococcosis ; pharmacokinetics ; protein binding
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of haemodialysis on mebendazole kinetics has been studied in a patient receiving both mebendazole therapy and haemodialysis. The procedure of haemodialysis did not influence the plasma concentration — time profiles or the mean daily plasma levels. The arterio-venous difference in the dialyser was negligible and no mebendazole could be detected in the dialysate. Protein binding of mebendazole was 90% before dialysis and 88% during dialysis and not significantly different from the binding in patients without renal disease (91.4±1.9%, n=22).
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  • 135
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 501-503 
    ISSN: 1432-1041
    Schlagwort(e): valpromide ; valproic acid ; pharmacokinetics ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of valpromide, a primary amide of valproic acid, was investigated in 6 healthy, adult male volunteers, each of whom was given 900 mg as a marketed, enteric-coated tablet and a solution. Valpromide was biotransformed to valproic acid after the administration of the tablet and the solution with a bioavailability of 0.79±0.24 and 0.77±0.12, respectively, relative to a marketed tablet of valproic acid. The absorption of valpromide was not rate-limited by dissolution. As a solid, non-hygroscopic, neutral prodrug of valproic acid, valpromide may be a good alternative to valproic acid and sodium valproate.
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  • 136
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 589-593 
    ISSN: 1432-1041
    Schlagwort(e): piretanide ; renal insufficiency ; furosemide ; pharmacokinetics ; loop diuretic
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of piretanide was studied in 10 patients with chronic renal failure. After administration of a high oral dose (12 to 192 mg) of piretanide the kinetics behaved according to an open 2-compartment model. The elimination constant in the first phase (α) ranged from 0.385 to 0.756 h−1 and in the second phase (β) from 0.079 to 0.274 h−1. The corresponding elimination half-lives ranged from 55 to 108 min (t1/2 α) and from 152 to 524 min (t1/2 β). Only an average of 2.8% of the orally administered drug was recovered in 24 h urines. Nevertheless, a good correlation was found between urinary recovery or renal clearance of the drug and residual renal function. The elimination of piretanide by non-renal mechanisms appeared to be increased when renal function was greatly diminished.
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  • 137
    ISSN: 1432-0738
    Schlagwort(e): TCDD ; 2,3,7,8-Tetrachlorodibenzo-p-dioxin ; 3-Methylcholanthrene ; Phenobarbital ; 2,3,7,8-Tetrabromodibenzo-p-dioxin ; Toxaphene ; 5-Chloro-2-(2,4-dichlorophenoxy)phenol ; 4,5,6-Trichloro-2-(2,4-dichlorophenoxy)phenol ; Vitamin A ; Retinol ; UDP-glucuronosyltransferase ; Aryl hydrocarbon hydroxylase ; Liver ; Rat ; High pressure liquid chromatography
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrabromodibenzo-p-dioxin (TBrDD), 5-chloro-2-(2,4-dichlorophenoxy)phenol(3-Cl-predioxin) 4,5,6-trichloro-2-(2,4-dichlorophenoxy)phenol (5-Cl-predioxin), toxaphene, 3-methylcholanthrene (3-MC) and phenobarbital (PB) on the vitamin A storage, UDP-glucuronosyltransferase (UDPGT) and aryl hydrocarbon hydroxylase (AHH) activities in the liver of Sprague-Dawley rats was investigated. Vitamin A was determined as retinol by high pressure liquid chromatography. UDPGT was measured with p-nitrophenol as an aglycone and AHH with 3,4-benzopyrene as a substrate. Both in TCDD- and toxaphene-treated animals a reduced body weight gain was recorded, but no other overt signs of toxicity were seen in this study. Both the concentration and the total amount of hepatic retinol was significantly reduced in TCDD-, 3-MC-, PB- and TBrDD-treated animals. These compounds were also those which gave the most significant enzyme induction as regards the UDPGT and AHH activities. However, the reduction of hepatic retinol caused by these compounds did not correlate with the enzyme activities studied. When compared on a molecular basis, TCDD and TBrDD were in the order of several magnitudes more potent as reducers of hepatic retinol and likewise as enzyme inducers.
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  • 138
    Digitale Medien
    Digitale Medien
    Springer
    Archives of toxicology 56 (1984), S. 59-65 
    ISSN: 1432-0738
    Schlagwort(e): Trialkylphosphorothioates ; Rat ; Lung ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The oral administration of an LD50 dose (25 mg/kg) of O,S,S-trimethyl phosphorodithioate to rats induced immediate, cholinergic symptoms. A delayed respiratory crisis followed, 3–4 days later, involving a pronounced increase in lung weight and extensive injury to the alveolar epithelium. This compound also induced the immediate liberation of secretory granules from the Clara cells. Minor changes in the surface appearance of these cells were also observed but no signs of injury were found in any cells of the bronchiolar epithelium. The complement of secretory granules was monitored, by the morphometric analysis of ultrathin sections. Clara cells from control animals were found to contain 9.55±1.16 (SEM) granules per cell profile. The Clara cells from dosed animals were largely devoid of granules until the 3rd day after administration. Many of these agranular cells were arranged in clusters and often showed signs of mitotic division. In surviving animals the subsequent replacement of granules resulted in a large increase in the numbers present and many exhibited abnormal morphology. Over twice the normal complement of granules, 22.45±0.42 (SEM) per cell profile, was found 6 days after dosing. The complement of granules subsequently returned to normal levels and the clusters of Clara cells were resolved within 14 days of dosing.
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  • 139
    Digitale Medien
    Digitale Medien
    Springer
    Archives of toxicology 56 (1984), S. 117-122 
    ISSN: 1432-0738
    Schlagwort(e): Rat ; Retinoids ; Bone alterations ; Adverse effects ; Arotinoid ethylsulfone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Repeated ingestion of high doses of retinoids cause the so-called hypervitaminosis A syndrome. In rats the main symptoms are weight loss, alopecia, erythema, desquamation of the skin, and alterations of the skeletal system, including bone fractures. In the present study, three retinoids (Ro 15-1570, arotinoid ethylsulfone, 6 mg/kg; retinoic acid, 100 mg/kg and etretinate, 50 mg/kg) were administered orally to rats for 1 and 2 weeks, respectively, to six male and six female rats/group. All the above changes were induced by all three retinoids, with the exception that the arotinoid ethylsulfone Ro 15-1570 did not cause bone alterations. The absence of toxic effects on the bones by Ro 15-1570 was confirmed by X-ray-film examinations, densitometry of the X-rayed femora and tibiae, examination of the thickness of the femoral and tibial compacta in histological slides plus the determination of the femoral ash weight and its main inorganic constituents (calcium, magnesium, sodium, and potassium). The present demonstration that the arotinoid ethylsulfone Ro 15-1570 was devoid of bone toxicity constitutes major progress in the pharmacologic development of retinoids with a better balance between therapeutic and adverse effects.
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  • 140
    ISSN: 1432-0738
    Schlagwort(e): Methyl mercury ; Toxicokinetics ; Differential toxicity ; Japanese quail ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Distribution of a single oral dose of methyl mercury (10 mg Hg/kg body weight) was followed from 90 min up to 120 h in plasma, erythrocytes, and brain of Japanese quails and rats. Significantly higher Hg concentrations were observed in plasma and brain of quails and red blood cells of rats. Blood/brain ratio decreased in quails from 6 to 2 at 24 h and 120 h respectively, whereas it increased in rats. Erythrocyte/plasma ratio in quails was about three times lower and averaged 54. The differences in Hg distribution were accompanied by a more than 3-fold higher acute toxicity in quails under adequate experimental conditions.
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  • 141
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 54 (1984), S. 437-445 
    ISSN: 1432-1106
    Schlagwort(e): Rat ; Spinal motoneurones ; Recurrent discharge ; Electrical synapse ; In vitro study
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The excitatory interaction between spinal motoneurones was investigated by means of electromyogram (EMG) recordings from hindlimb muscles as well as intracellular ones from their innervating motoneurones in the isolated preparation of immature rats. Stimulation of the muscle nerve to biceps femoris or medial gastrocnemius or of the L5 ventral root evoked early and late EMG responses in the muscle of the preparations with the dorsal roots cut. The early response was produced directly by volleys in the motor nerve. The late response was of spinal origin, since it disappeared after the severance of the ventral root. The thresholds and the conduction velocities of nerve fibres, which conducted the centripetal impulse causing the late response, were compatible with those of motor nerve fibres. The amplitude of the late response was 5–10% of that of the maximum early EMG response. Intracellular recordings from spinal motoneurones revealed that stimulation of the ventral root elicited the double discharge composed of antidromic and delayed spike potentials. The delayed spike was never evoked after the spike potential elicited directly by a short depolarizing pulse. The double discharge was observed in about 6% of the motoneurones examined. The threshold of the stimulus intensity evoking the double discharge was in the range of those of motor nerve fibres. The latencies of the delayed excitation were 7.0–9.0 ms, comparable to the intraspinal delays of the late EMG response. Stimulation of the ventral root at intensities subthreshold for antidromic activation was found to produce a small depolarizing potential in about 60% of the motoneurones examined. The amplitudes were 0.5–5.0 mV, and the onset and the peak latencies 2.0–7.0 ms and 5.0–8.0 ms, respectively. The potential was unaffected by the deficiency of calcium ions in the perfusing medium and persisted after the degeneration of the afferent fibres in the ventral root. It was thus concluded that the depolarizing potential was generated by electrical synapses between motoneurones. In a few motoneurones the electrical synaptic potential was found to elicit spike potentials. Latencies of these spikes were similar to those of the delayed excitation in motoneurones with the double discharge. The time course of changes in the excitability in these motoneurones showed that the delayed excitation, hence the late EMG response, was also caused by the electrical synaptic potential.
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  • 142
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 55 (1984), S. 368-371 
    ISSN: 1432-1106
    Schlagwort(e): Simple spike ; Purkinje cell ; Inferior olive lesion ; Rat ; Plasticity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In recent experiments Montarolo et al. (1982) have shown that reversible inferior olive (IO) inactivation of up to 90 s induces a marked increase of the Purkinje cell (PC) simple spike (SS) frequency which lasts as long as the disappearance of the complex spikes (CS). The present work was aimed at studying how long this SS frequency increase lasts. We recorded the electrical activity of 724 PCs from rats (Nembutal anaesthesia 20–40 mg/kg) in which the IO was destroyed by means of cryocoagulation, electrocoagulation and 3-acetylpyridine injection. The SS activity was followed up to 1 month from the lesion. The average SS frequency of the first 5 days is 52.7 (±22.6 S.D.). The difference from the control (22.6±13.7 S.D.) is highly significant (P〈 0.001; Mann-Whitney U-test). Later the SS discharge shows a gradual decrease, to reach a value (24.2±12.1 S.D.) similar to the control at the 4th week. Our results demonstrate that the increase of the SS activity, due to the IO lesion, undergoes an adaptation. The time course of such an adaptation is well correlated with the metabolic changes in the intracerebellar nuclei, following an IO permanent lesion, described by Bardin et al. (1983).
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  • 143
    ISSN: 1432-1106
    Schlagwort(e): Lateral ; Interposed nuclei ; Ipsilateral descending B.C. ; Lateral parvocellular reticular formation ; Trigeminal complex ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The distribution, organization and origin of the ipsilateral descending limb of the Brachium Conjunctivum (B.C.), have been studied in the rat by using anterograde and retrograde tracing techniques. After injections of tritiated leucine/proline into the lateral cerebellar nucleus, covering both its medial part, corresponding to the dorsolateral hump (DLH) of Goodman et al. (1963) and its lateral part, (designated here as the lateral dentate, LD), and the neighboring interposed nucleus (NI), emerging fibres are numerous and leave laterally from the B.C. On the contrary, injections restricted to LD reveal very few such fibers. Within the lateral parvocellular reticular formation (LPRF) terminal labelling is heavy, and moderate to sparse within the adjacent trigeminal complex. Rostro-caudally, silver grain accumulation within the LPRF extends from the level of the motor trigeminal nucleus (VM) to the pyramidal decussation, exhibiting a cephalocaudal decrease of grain density. Within the trigeminal complex, labelling occurs in the caudal VM, the dorsal portion of the principal sensory nucleus, and within and around the trigeminal spinalis oralis. In addition, the area surrounding the VM (in part corresponding to the supratrigeminal region of Lorente de Nó 1922, 1933) is moderately labelled. After injections of HRP into various levels of the ipsilateral descending B.C.'s projection field, retrogradely labelled cells are numerous within the DLH. A slightly lesser amount of labelled cells are found in the lateral half of the NI, primarily concerning the nucleus interpositus posterior. Within the LD, only a few labelled cells are observed: these are mainly restricted to the dorsal portion at rostral levels of the nucleus. The results obtained by both the anterograde and retrograde studies suggest an absence of a topographic organization within this descending B.C. component. The possible functional meaning of these results is discussed.
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  • 144
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 56 (1984), S. 502-508 
    ISSN: 1432-1106
    Schlagwort(e): Visual system ; Retinopetal cells ; Lateral mesencephalic tegmentum ; Retrograde tracing ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The centrifugal innervation of the retina was reinvestigated in albino and pigmented rats with intraocular injections of horseradish peroxidase (HRP), radioactive wheat germ agglutinin (WGA) and proline. No labeled cells were found in the brains injected with HRP and proline, except some eye muscle motoneurons in one case apparently involving orbital contamination from the injection. In the cases injected with WGA and having a survival time of at least two days cells were labeled in the lateral mesencephalic tegmentum, ventral to the parabigeminal nucleus and in the periaqueductal gray. Both these findings are most likely due to transneuronal anterograde-retrograde transport of the tracer through the superior colliculus. The results yielded no compelling evidence for the existence of a direct retinopetal pathway in the rat, which is in contrast to a recently claimed retinal projection originating from the pretectum. Special attention was paid to the labeling in the lateral mesencephalic tegmentum, an area giving rise to retinal projections in various submammalian species. This finding is discussed with regard to the possibility that also in the rat the lateral tegmentum exerts an early influence on visual input, but at the “higher” collicular level and not at the “original” retinal one.
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  • 145
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 54 (1984), S. 1-6 
    ISSN: 1432-1106
    Schlagwort(e): ACTH ; Urethane ; Corticosterone ; Rat ; Electrical stimulation ; Pituitary-adrenal function
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The effect of limbic forebrain stimulation on pituitary-adrenal function was assessed by evaluating plasma corticosterone obtained prior to and following sham or electrical stimulation of urethane (1.20 g/kg) anesthetized female rats. Cortical electroencephalogram (EEG), electrocardiogram (ECG), heart rate (HR), mean arterial blood pressure (MAP), and respiration were routinely monitored. Timed blood samples (0.25 ml) were obtained from a catherized femoral artery. The HR (Bts/min), MAP (mm of Hg), and corticosterone levels (μg/dl) for 7 non-stimulated rats averaged over 6 sampling periods were 385±19, 95±6, and 70.3±5.8 respectively. In electrically or sham stimulated rats, blood samples were taken just prior to stimulation (biphasic square waves, 100 μA, 50 or 60 Hz, 1 ms, 1 s on/1 s off for 15 or 30 min) and 5, 10, 15, and 30 min after initiation of stimulation. Significant changes in plasma corticosterone levels were obtained following stimulation of hippocampal and amygdaloid areas. In contrast, no change in corticosterone concentration was observed following stimulation of cortex, corpus callosum, fornix and a variety of other CNS areas. Detailed analysis of hippocampal influence on urethane stimulated plasma corticosterone levels showed increased plasma corticosterone levels following stimulation of CA1. In contrast, stimulation of CA3, dentate (includes CA4) and the subiculum produced significant decreases in plasma corticosterone levels. No change in corticosterone levels was observed following sham stimulation. Collectively, these data indicate that consideration must be given to the possibility that differential neuroendocrine regulatory mechanisms reside within various limbic forebrain complexes and that electrical stimulation of limbic forebrain sites of urethane anesthetized rats may provide information regarding sites inhibitory to pituitary-adrenal activity.
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  • 146
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 54 (1984), S. 337-348 
    ISSN: 1432-1106
    Schlagwort(e): Optokinetic pathways ; Pretectum ; Prepositus hypoglossi complex ; N. reticularis tegmenti pontis ; Vestibular nuclei ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 1) Intra-and extracellular responses of neurons in the pretectum (Pt), the nucleus reticularis tegmenti pontis (NRTP), the prepositus hypoglossal complex (NPH) and the vestibular nuclei (VN) were recorded during orthodromic/antidromic stimulation of their afferent/efferent fibers. 2) In the Pt, many neurons were excited by stimulation of the contralateral optic nerve (ONc). Comparison of the latencies of evoked presynaptic action potentials and EPSPs yielded a time difference corresponding to one synaptic delay. Forty five per cent of these monosynaptically driven neurons were also excited antidromically from the ipsilateral NRTP. 3) In the NRTP, ONc and Pt stimulations evoked disynaptic and monosynaptic EPSPs, respectively. Thirty six per cent of NRTP neurons orthodromically driven from ONc and/or ipsilateral Pt stimulation were also antidromically invaded from either the contralateral (67%) or the ipsilateral (33%) flocculus but never from both. 4) In the NPH, both ipsilateral Pt and NRTP stimulations excited type II neurons monosynaptically. In addition, EPSPs evoked by Pt stimulation could be mediated to the NPH via a disynaptic route involving the NRTP. 5) In the VN, type II neurons were excited by ipsilateral Pt stimulation. When comparing the latencies of action potentials and EPSPs evoked by Pt stimulation in the NPH and in VN type II neurons respectively, a short, possibly monosynaptic connection, may be postulated between the NPH and the VN. 6) Our results suggest that vestibular neurons may be optokinetically driven from the contralateral eye both via Pt-NPH connections and Pt-NRTP-NPH paths. They also confirm the existence of a transcerebellar route from the Pt via the NRTP to the ipsior contralateral flocculi.
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  • 147
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 55 (1984), S. 515-522 
    ISSN: 1432-1106
    Schlagwort(e): Rat ; Serotonin ; Immunocytochemistry ; Trigeminal nuclear complex
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The distribution of serotonin immunoreactive (5-HT-IR) fibers in the trigeminal nuclear complex of the rat was mapped. In the sensory nuclei, innervation appeared to be dense in areas primarily related to nociceptive afferent activity, and sparse in areas primarily related to nonnociceptive afferent activity. Specifically, the marginal and gelatinosa layers of the spinal subnucleus caudalis contained many 5-HT-IR fibers while few labeled fibers were seen in the magnocellular portion of subnucleus caudalis or in the principal sensory nucleus. The spinal subnuclei oralis and interpolaris were sparsely innervated except for a few areas which contained more 5-HT-IR fibers. The motor nucleus contained as many immunoreactive fibers as the subnucleus caudalis, although fibers in the motor nucleus were thicker and varicosities more irregularly spaced than in caudalis.
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  • 148
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 55 (1984), S. 553-561 
    ISSN: 1432-1106
    Schlagwort(e): Thalamus ; Electrophysiology ; Iontophoresis ; Acetylcholine ; Choline acetyltransferase ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Several lines of evidence suggest a role for ACh in the mediation of cerebello-thalamic transmission. The physiological, pharmacological and biochemical experiments described were designed to test this hypothesis for the rat cerebello-thalamic pathway. Unilateral electrolytic lesions of the superior cerebellar peduncle resulted in modest falls of CAT from both ventromedial thalamic nuclei (contralateral 35%, ipsilateral 15%). Iontophoretic application of ACh to relay cells evokes three types of response (i) excitation (ii) inhibition (iii) polyphasic combinations of (i) and (ii). The type of response evoked was directly related to the firing pattern of the cell. Thus, for example, excitatory responses were never recorded during high-frequency bursting but were easily evoked following a switch to tonic, single-spike activity. All responses to ACh and synaptic responses to cerebellar stimulation were sensitive to muscarinic but not to nicotinic cholinergic antagonists. The nicotinic antagonist mecamylamine was a potent blocker of excitant amino acid responses but had no effect on cerebellarevoked synaptic responses. Cholinergic and anticholinergic agents had a profound action on relay cell firing pattern. ACh promoted single-spike activity whereas atropine promoted high-frequency bursting. The actions of ACh are discussed with reference to recently discovered voltage-sensitive ionic conductances. Because of the modulatory action of ACh on relay cell firing pattern and excitability no firm conclusion can be reached concerning the hypothesis under test here. We tentatively suggest a dual role for ACh as both neurotransmitter and neuromodulator.
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  • 149
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 55 (1984), S. 535-552 
    ISSN: 1432-1106
    Schlagwort(e): Thalamus ; Cerebellum ; Basal ganglia ; Electrophysiology ; Rat ; Firing patterns ; Transmission
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary On the basis of antidromic stimulation we have identified two distinct neuronal populations in the rat ventromedial thalamic nucleus. The largest population (96%) are thalamo-cortical relay cells which project via the internal capsule to the cerebral cortex. The smaller population of cells (4%) project caudally to the reticular formation and superior colliculus. These two cell types could be distinguished further on the basis of their patterns of spontaneous discharge. Relay cells fluctuate between two activity patterns (i) a rhythmic pattern characterized by periods of high-frequency bursting, and (ii) a more tonic discharge pattern of single spikes. The caudally projecting cells had a characteristic fast, regular type of spontaneous firing. Brachium conjunctivum stimulation evokes two distinct responses in thalamic relay cells, (i) a short-latency single spike, (ii) a longer latency, rhythmic response of 2–3 spikes. Both excitatory responses are followed by a period of cell quiescence. The type of response is dependent upon the cell's firing pattern. The short-latency response occurs during tonic, single-spike activity whilst the longer latency response occurs during highfrequency bursting activity. The short-latency response can be altered to the long latency response by increasing the level of anaesthesia or by applying a conditioning shock to known inhibitory pathways. Conversely the long latency response can be altered to the short-latency response by decreasing anaesthesia or by stimulation of the reticular formation. It is argued that both response types are evoked monosynaptically by activation of the same cerebello-thalamic fibres but that different ionic conductances which are active at different levels of membrane polarization are responsible for the two response patterns. Efficient time-locked cerebellothalamo-cortical transmission occurs only during tonic single-spike activity, when cerebellar stimulation evokes a short-latency response. Such transmission is allowed or disallowed by the fine balance between converging excitatory and inhibitory afferents. In addition to a monosynaptic excitatory input from the cerebellar nuclei, relay cells received converging synaptic inputs from the substantia nigra, cerebral cortex, reticular formation and superior colliculus. Due to the anatomical arrangement in the rat it proved impossible to assess the role of the pallidum. The population of caudally projecting cells also received several converging synaptic inputs, but unlike those influencing relay cells, these inputs were all excitatory. We have obtained no clear physiological evidence for the occurrence of local interneurones within the ventromedial nucleus. However, a powerful recurrent inhibitory circuit is activated following antidromic activation of relay cells. The interneurones responsible for this inhibition appear to lie in the thalamic nucleus reticularis.
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  • 150
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 55 (1984), S. 579-585 
    ISSN: 1432-1106
    Schlagwort(e): Septo-Hippocampal projections ; Hippocampal afferents ; Cholinergic projections ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In a series of experiments in which the known projections of the septal complex to the hippocampal formation have been transected, we have used both anterograde and retrograde tracing techniques in an attempt to demonstrate a ventral septo-hippocampal pathway. In cases where transections of the fimbria, dorsal fornix and supracallosal stria were complete, injections of the retrograde tracers wheat germ agglutinin-conjugated horseradish peroxidase or Fast blue, resulted in labeled cells in the ipsilateral septal complex, primarily in the nucleus of the diagonal band. The number of cells labeled in these experiments was approximately 5–10% of that seen in experiments in animals with intact dorsal pathways who had received similar injections. The presence of a ventral pathway was confirmed in anterograde labeling experiments in which injections of 3H-amino acids were made into the septal complex. The autoradiogfaphs demonstrated that the projection terminates most heavily in the entorhinal cortex and to a lesser extent in the ventral subicular complex; there may be an additional minor projection to the temporal half of the hippocampus and dentate gyrus. Finally, using double labeling procedures, we were able to demonstrate that at least a portion of the cell population that gives rise to the ventral pathway demonstrates choline acetyltransferase immunoreactivity and is presumably cholinergic.
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  • 151
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 57 (1984), S. 107-117 
    ISSN: 1432-1106
    Schlagwort(e): Development ; Rat ; Optic nerve ; Cell death ; Myelination ; Eye removal
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In the albino rat, the number of optic axons increases from 400 on embryonic day 15 to reach a peak of 240000 at birth, before declining to adult numbers (100000) by postnatal day 5. Throughout the period of loss of axons there are few signs of degeneration in the optic nerve, which does not change its diameter: the decrease in density of axons is matched by an increase in the cross-sectional area of individual axons. Myelination of the initially non-myelinated axons starts on day 5, when axonal numbers stabilize. Following neonatal removal of one eye, fewer axons than normal are present in the contralateral optic nerve up to day 5. The axons removed by enucleation may be retino-retinal axons, representing up to 40% of the 83000 fibres lost between postnatal days 2 and 5. There is no increase in the numbers of optic axons in the remaining nerve in adult animals; this appears to be due to the small absolute numbers of ipsilateral axons saved by enucleation. After enucleation, axons remain clear and undergo a “watery” degeneration after initially swelling, and the removal of degenerative products is accomplished within four days.
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  • 152
    ISSN: 1432-1106
    Schlagwort(e): Harmaline tremor ; Cerebellum ; Inferior olive ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Purkinje cells were recorded extracellularly and mapped in the cerebellar cortex of the rat under tremogenic doses of harmaline. Four différent types of responses were encountered, of which two were considered as being responsible for the harmaline tremor. The latter had a regular firing pattern of complex spikes at 5 to 10 Hz and were mostly found in the vermis. Their number decreased in the more lateral region of the cerebellar cortex until they eventually disappeared. Horseradish peroxidase was injected into all the areas of the cerebellar cortex containing Purkinje cells with harmaline-induced activity. Labeled neurons were in all cases traced to the medial accessory olive. The metabolic activity of the inferior olive under harmaline was measured with 2-deoxyglucose. Increased labeling was only found in the medial accessory olive. Such an increase was demonstrated as being due to a direct effect of the drug on the inferior olivary neurons, indicating that the medial accessory olive is responsible for the harmaline tremor in the rat. Our results point out that, in the rat, there is an inverse relationship between serotoninergic innervation of a region in the inferior olivary nucleus and that with harmaline sensitivity, therefore a serotoninergic mechanism hypothesis for the harmaline tremor needs further investigation.
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  • 153
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 53 (1984), S. 341-348 
    ISSN: 1432-1106
    Schlagwort(e): Supraoptic nucleus ; Nucleus accumbens ; Septum ; Vasopressin ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Synaptic inputs from the nucleus accumbens (ACB) to neurosecretory cells of the supraoptic nucleus (SON) were studied in the rat. One hundred and twenty SON neurones responded antidromically to pituitary stalk stimulation and were identified as neurosecretory cells. Sixty-three of these cells were identified as vasopressin-secreting cells and 45 as oxytocin-secreting cells by their spontaneous firing patterns. About one half of the vasopressin-cells and two thirds of the oxytocin-cells were responsive to stimulation of the basal forebrain including the ACB. More vasopressin-cells were excited than were inhibited, and oxytocin-cells were mainly inhibited. Depth profile of effective stimulation sites in the basal forebrain revealed that ACB stimulation selectively produced the responses. Most of those SON neurones responsive to ACB stimulation also responded to septal stimulation. A positive correlation was observed between responses to ACB and septal stimulation in each unit. After septal lesion, the number of SON neurones which were responsive to ACB stimulation was significantly decreased. In two rats, a single SON unit was tested for ACB stimulation both before and after septal lesion, and the previously observed synaptic inputs were not seen after the lesion. Fifty septal neurones projecting to the area including the SON were antidromically identified after SON stimulation. About one half of these neurones were excited by ACB stimulation. These results demonstrate the existence of a neural pathway from the ACB to the SON and suggest that the pathway is mediated by septal neurones.
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  • 154
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 54 (1984), S. 499-512 
    ISSN: 1432-1106
    Schlagwort(e): Parataenial nucleus ; Nucleus accumbens ; Autoradiography ; Thalamus ; Limbic system ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In this study the intrastriatal distribution of afferents arising from the parataenial nucleus of the thalamus was investigated. Tritiated leucine and proline injected into the parataenial nucleus was found to densely label the entire anterior-posterior extent of the medial nucleus accumbens. The projection was for the most part limited to this striatal subregion, although some moderate labelling was found along the medial wall of the anterior caudateputamen. The terminal labelling within accumbens was characterized by a distinct patchiness. Other efferent connections of the parataenial nucleus observed in this study include the thalamic reticular nucleus, the basolateral and central nuclei of the amygdala, the septum, the medial frontal cortex, the entorhinal cortex and subiculum. This projection is distributed to the “limbic afferented” sector of striatum, and there is a nearly complete overlap between the parataenial afferents and those coming from hippocampus. The present findings suggest that the parataenial nucleus is an important thalamic link between limbic and striatal processing.
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  • 155
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 56 (1984), S. 144-148 
    ISSN: 1432-1106
    Schlagwort(e): Rat ; Parabigeminal nucleus ; Superior colliculus ; Lateral geniculate nucleus ; HRP
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The retino-recipient layers of the superior colliculus project predominantly to the dorsal and ventral divisions of the ipsilateral parabigeminal nucleus, while receiving an input chiefly from the medial division of the contralateral nucleus. A variety of retrograde tracing techniques was used to confirm that there is a projection from the medial division of the parabigeminal nucleus to the contralateral dorsal lateral geniculate nucleus in normal adult hooded rats. Some parabigeminal cells branch to supply both dorsal lateral geniculate nucleus and retino-recipient layers of the superior colliculus.
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  • 156
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 53 (1984), S. 223-232 
    ISSN: 1432-1106
    Schlagwort(e): Cortico-geniculate influence ; Lateral geniculate nucleus ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Unitary discharges of the lateral geniculate nucleus (LGN) were analyzed in anesthetized and paralyzed rats after inactivation of visual cortical areas (VC) by cryoblockade or by depositing a cotton wick soaked in KCl (3 M). The receptive fields were mapped prior to and following the interruption of the cortico-geniculate feedback. The responsiveness of the VC was controlled by monitoring evoked potentials and the EEG. In most off-center and about half on-center cells the surround excitatory responses were markedly reduced and even totally abolished. In contrast, the center excitation remained unchanged or increased suggesting a parallel decline of the inhibitory surround. This differential influence of cortical blockade on on- or off-responses failed to appear in on-off cells whose receptive field was nonconcentrically organized. It is proposed that the VC exerts a complex influence upon geniculate physiology while the spatial center-surround relationships are under the control of the VC. The results of this investigation are comparable to those obtained in rabbits and cats.
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  • 157
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 55 (1984), S. 455-461 
    ISSN: 1432-1106
    Schlagwort(e): Rat ; Pineal gland ; Pinealocyte ; Rhythms ; Circadian rhythm ; Electrical activity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Extracellular single-unit recordings were made during day- and night-time in the pineal gland of urethane-anesthetized adult male Sprague-Dawley rats. All cells exhibiting spontaneous electrical activity had firing frequencies from less than 1 Hz to about 100 Hz, and their discharge patterns were characterized as regular, irregular or bursting. While most of the spontaneously active cells (n=63) showed a uniform activity level throughout the recording period (30–120 min), a group of 9 cells exhibited oscillatory rhythms with periods of 4–8 min. In addition, long-term recordings across day- and night-time from five cells revealed increasing activity during night-time in three cells, while the remaining two units showed constant activity throughout the recording time (8–20 h). Comparison of day- and night-data in general indicated an overall higher level of activity at night.
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  • 158
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 53 (1984), S. 374-383 
    ISSN: 1432-1106
    Schlagwort(e): Visual cortex ; Visual field properties ; Rat ; Vision
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Response properties of neurons in the visual cortex, area 17, of Long Evans pigmented rats were investigated quantitatively with computer-controlled stimuli. Ninety percent of the cells recorded (296/327) were responsive to visual stimulation. The majority (95%, 281/296) responded to moving images and were classified as complex (44%), simple (27%), hypercomplex (13%) and non-oriented (16%) according to criteria previously established for cortical cells in the cat and monkey. The remaining 5% of the neurons responded only to stationary stimuli flashed on-off in their receptive field. Results of this study indicate that neurons of the rat visual cortex have properties similar to those of cells in the striate cortex of more ‘visual’ mammals.
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  • 159
    ISSN: 1432-1106
    Schlagwort(e): Cat ; Rat ; Spinal tract neurons ; Retrograde HRP transport ; Procedure and evaluation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Modifications have been made in Mesulam's method for labelling neurons by retrograde transport of horseradish peroxidase, with tetramethylbenzidine as chromogen, with the object of increasing the extent of labelling of dendrites and axons. A procedure was devised specifically for studying spinomedullary and medullospinal tract systems, involving implanting easily-made HRP-agar pellets into areas of controlled damage in particular spinal fascicles, and sealing the site of implant with cyanoacrylate glue. Lesions of other fascicles were often made to limit transport to the implanted fascicle. Fourth-order dendrites were regularly labelled over long (30 cm or more) transport distances: axons were also labelled over this whole distance, often allowing exact study of the initial course of particular axons. Controls in both cat and rat showed that the uptake of HRP under these circumstances occurred almost wholly from the region of axonal damage at the site of implant which can be characterized histologically.
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  • 160
    Digitale Medien
    Digitale Medien
    Springer
    Pflügers Archiv 401 (1984), S. 71-76 
    ISSN: 1432-2013
    Schlagwort(e): Cardiac anoxia ; Enzyme release ; Reoxygenation damage ; Mitochondrial swelling ; Contracture development ; Cell lysis ; Adult heart cells ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Cultured adult cardiac myocytes were exposed to anoxia under substrate-free conditions and then reoxygenated. When comparing the oxygen deficient organ to the anoxic cell culture, we see that metabolic changes in the latter system proceed in a similar, yet prolonged manner, as in arrested hearts. Release of cytosolic enzymes starts with minor energetic disturbances and proceeds closely correlated to the actual ATP level. Below 2 μmol ATP/gww, an increasing number of cells becomes irreversibly damaged, above this level, 30 min reoxygenation leads to extensive recovery of the whole preparation. The results indicate that leakage of cytosolic enzymes during the early stage of anoxia is due to a gradual protein release from the individual cells and is related to reversible membrane alterations. Reoxygenation does not induce changes considered typical of the ‘oxygen paradox’. Since mechanical cell-cell interactions are absent in this model, it is suggested that aggravation of tissue damage in heart tissue reoxygenated late is mainly caused by mechanical forces.
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  • 161
    ISSN: 1432-2072
    Schlagwort(e): Noradrenaline ; Serotonin ; Dopamine ; Beta receptors ; Antidepressants ; Thiopentone ; Anaesthesia ; Rat ; Iprindole ; Mianserin ; Zimelidine ; Sleeping time
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A behavioural model sensitive to manipulation of brain noradrenaline systems and with characteristics of beta-receptor mediation has been developed using the duration of thiopentone anaesthesia in the rat. Acute and chronic administration of various antidepressant agents was examined. In the acute phase, (30 min prior to thiopentone) the noradrenaline uptake-inhibiting tricyclic drugs and viloxazine increased anaesthesia duration in a dose-dependent fashion. The atypical antidepressants trazodone, iprindole, and mianserin did this only weakly, while the dopaminergic and serotonergic uptake-inhibiting antidepressants (respectively bupropion, nomifensine, and zimelidine, fluoxetine) markedly shortened anaesthesia duration. Chronic administration (for 15 days) prolonged anaesthesia duration measured 2 or 5 days after the last drug injection for all tricyclic agents, for the atypical antidepressants mianserin, iprindole, fluoxetine, and zimelidine, and for viloxazine.
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  • 162
    ISSN: 1432-2072
    Schlagwort(e): Conditioned reinforcement ; d-Amphetamine ; Nucleus accumbens ; Caudate nucleus ; Thalamus ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Stimulant drugs have been shown to enhance the control over behaviour exerted by stimuli previously correlated with primary reinforcers, termed conditioned reinforcers (CR). Experiment 1 examined the possible neuroanatomical specificity of the enhancement of conditioned reinforcement following intracerebral injections ofd-amphetamine. Thirsty rats were trained to associate, a light with water. In the test phase, water was no longer presented but the light (CR) was intermittently produced by responding on one of two novel levers. Rats with bilateral guide cannulae aimed at the nucleus accumbens, posterior caudate nucleus, or medio-dorsal nucleus of the thalamus received four counterbalanced microinfusions ofd-amphetamine (10, 20, 30 μg/2 μl) or vehicle (control) over 4 test days. There was a dose-dependent selective increase in responding on the lever that produced the light (CR) with intra-accumbensd-amphetamine infusions. Quantitatively similar, but much more variable effects were found with intra-caudate infusions and no effects following intra-thalamicd-amphetamine. Experiment 2 provided evidence that the enhanced control over responding by a CR with intra-accumbensd-amphetamine is behaviourally specific. Three groups of rats received a compound tone — plus —light stimulus that was positively, negatively or randomly correlated with water during training. Intra-accumbensd-amphetamine produced selective increases in responding only if the contingent stimulus had been positively correlated. The results suggest that the nucleus accumbens may play an important role ind-amphetamine's enhanced control over behaviour exerted by conditioned reinforcers.
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  • 163
    ISSN: 1432-2072
    Schlagwort(e): Citalopram ; Antidepressant ; Long-term treatment ; Hypermotility ; Dopamine receptors ; Serotonin receptors ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effect of prolonged administration of the potent and specific 5-HT uptake inhibitor citalopram on behavioural measures of dopaminergic and serotonergic activity has been studied in rats. Administration of citalopram in the diet at a daily dose of 99 μmol/kg led to supersensitivity to d-amphetamine-induced hypermotility and stereotypy and to subsensitivity to apomorphine-induced hypomotility 2 h after withdrawal. Forepaw clonus induced by 5-methoxy-N,N-dimethyltryptamine was decreased 2 h and 24 h after withdrawal and the number of head shakes induced by 1-5-HTP and citalopram were decreased 24 h after withdrawal. The d-amphetamine potentiation was still seen after 24 h, whereas the response had returned to normal 3 and 7 days after withdrawal. The content of amphetamine in three different brain regions was about 50% higher compared with controls 24 h after withdrawal of prolonged citalopram administration. At this time citalopram had been eliminated, and citalopram itself could not affect amphetamine metabolism. Other experiments indicated a linear relation between d-amphetamine brain concentration and motility level. Thus, a 50% increase in citalopram-treated rats cannot alone account for 3-fold increase in d-amphetamine-induced motility. Potentiation of d-amphetamine-induced hypermotility was also found after citalopram in a daily dietary dose of 25 μmol/kg for 13 days and after oral bolus injection (49 μmol/kg twice daily for 14 days). Acute citalopram injection had no effect in any of these models. The results suggest increased responsiveness of dopaminergic mechanisms mediating hypermotility, and decreased sensitivity of dopamine receptors mediating sedation (proposed autoreceptors). Sensitivity of 5-HT receptors was also decreased. The mechanisms by which citalopram induces d-amphetamine supersensitivity as well as subsensitivity to apomorphine and 5-HT agonists are presently unknown, since no changes in dopaminergic and serotonergic receptor binding have been found after an identical dose regimen.
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  • 164
    ISSN: 1432-2072
    Schlagwort(e): Rotational behavior ; Amphetamine ; Apomorphine ; Sensitization ; Sex differences ; Gonadal hormones ; Reverse tolerance ; 6-Hydroxydopamine ; Amphetamine psychosis ; Conditioning ; Dopamine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Factors influencing the behavioral sensitization (“reverse tolerance”) produced by intermittent amphetamine (AMPH) injections were studied by quantifying rotational behavior in rats that had a unilateral 6-hydroxydopamine lesion of the substantia nigra. The results indicate that (1) a single injection of a low dose of AMPH enhances rotational behavior induced by a second injection of AMPH for up to 12 weeks; (2) multiple, weekly injections of AMPH produce a progressive enhancement in rotational behavior, over-and-above that produced by a single injection; (3) female rats show more robust sensitization than males following single or multiple injections of AMPH; (4) this sex difference may be due to the suppression of sensitization by an androgen, because removal of testicular hormones potentiates sensitization; (5) the long-lasting sensitization of rotational behavior produced by infrequent injections of AMPH is not due to drug-environment conditioning effects, but perhaps to a persistent AMPH-induced change(s) in brain catecholamine systems; and (6) a simple change in DA receptors is probably no involved, because the sensitization produced by infrequent injections of AMPH does not influence the rotation produced by a subsequent injection of apomorphine. The results illustrate an intriguing example of neuroplasticity that may have clinical relevance.
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  • 165
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 84 (1984), S. 556-560 
    ISSN: 1432-2072
    Schlagwort(e): (Δ 1-THC) ; Cannabidiol (CBD) ; Open field behavior ; Psychotomimetic action ; Circling behavior ; Rotation ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Relatively high dosages of Δ 1-tetrahydrocannabinol (Δ 1-THC) markedly suppressed almost all normally occurring behavioral elements in rats as observed in both a small and a large open field. This effect persisted following repeated treatment and testing for 3 consecutive days. The psychotropically inert but related compound cannabidiol (CBD) did not suppress behavior, but in contrast had a mild activating effect. Both compounds decreased defecation during the test procedure. In addition, Δ 1-THC, but not CBD, induced a bizarre circling and turning response, that was evident over all 3 test days and occurred even when the rats were deeply sedated. It is suggested that an analysis of this phenomenon may be useful in measuring the psychotominetic action of Δ 1-THC and similar compounds in rats.
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  • 166
    ISSN: 1432-2072
    Schlagwort(e): Naloxone ; Methamphetamine ; Apomorphine ; Haloperidol ; Stereotypy ; Catalepsy ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Pretreatment with the opiate antagonist naloxone, at 1.25–5 mg/kg, increased the intensity of methamphetamine stereotypy, had no effect (over a range of 0.3125–5 mg/kg) on apomorphine stereotypy, and antagonized haloperidol catalepsy in rats at 1.25–5 mg/kg. It is suggested that naloxone, by blocking the opiate receptors located on the nigro-striatal and mesolimbic dopamine (DA) nerve terminals, releases the DA systems from endogenous inhibition, presumably caused by endogenous opiate systems, and thereby potentiates methamphetamine stereotypy and antagonizes haloperidol catalepsy. However, the possibility that naloxone might have affected methamphetamine stereotypy and haloperidol catalepsy by modulating the activity of the central noradrenergic and GABAergic systems, which are reported to influence dopaminergically mediated behaviours, also needs to be considered.
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  • 167
    ISSN: 1432-2072
    Schlagwort(e): Punishment-induced suppression ; Diazepam ; Serotonin ; Dorsal raphé ; Substantia nigra ; 5,7-Dihydroxytryptamine ; Ro 15-1788 ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effects of manipulating central serotonergic transmission were assessed on the anti-punishment effects of diazepam (2 mg/kg IP) in rats. In a paradigm involving the inhibition of pressing for food induced by the delivery of a signal previously associated with electric foot-shocks, lesioning serotonergic neurons of the dorsal raphé with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 1 μg in 0.4 μl) neither affected behavioral inhibition in control rats nor modified the ability of diazepam to release responding. Furthermore, suppression of pressing for food induced by a fixed ratio 7 schedule of shock presentation was reduced by bilateral infusion of 5,7-DHT (2 μg in 0.5 μl) into the substantia nigra, but the ability of diazepam to increase punished responding was preserved. Finally, blockade of benzodiazepine-induced decrease in serotonin release by application of the benzodiazepine receptor antagonist Ro 15-1788 (10−5–10−4 M in 0.2 μl) into the dorsal raphé did not alter the releasing effect of diazepam on suppression of pressing for food caused by a signal of punishment. At these concentrations. Ro 15-1788 was devoid of any effect on behavioral inhibition in control rats. Taken together, these results indicate that the anti-punishment activity of benzodiazepines can be dissociated from the reduction in tryptaminergic transmission produced by these drugs.
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  • 168
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 83 (1984), S. 194-199 
    ISSN: 1432-2072
    Schlagwort(e): Chronic amphetamine ; Latent inhibition ; Conditioned suppression ; Schizophrenia ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The animal amphetamine model of schizophrenia has been based primarily on stereotyped behavior. The present study sought to demonstrate an amphetamine-induced deficit in attentional processes. To this end, the effects of acute and chronic (14 days) 1.5 mg/kg dl-amphetamine administration on the ability of rats to ignore irrelevant stimuli were examined using the paradigm of latent inhibition (LI) in a conditioned emotional response (CER) procedure. The procedure consisted of three stages: pre-exposure, in which the to-be-conditoned stimulus, tone, was presented without being followed by reinforcement; acquisition, in which the pre-exposed tone was paired with shock; and test, in which LI was indexed by animals' suppression of licking during tone presentation. Experiment 1 showed that chronic but not acute treatment abolished LI. Experiment 2 showed that animals receiving chronic amphetamine pretreatment but pre-exposed and conditioned without the drug, exhibited normal LI. In Experiment 3, animals which received chronic amphetamine pretreatment and were pre-exposed under the drug but conditioned without it, also showed normal LI. The implications of these results for the animal amphetamine model of schizophrenia are discussed.
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  • 169
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 83 (1984), S. 257-261 
    ISSN: 1432-2072
    Schlagwort(e): Drug discrimination ; Reinforcement variables ; Fentanyl ; Morphine ; Sufentanil ; Naloxone ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rats were trained to discriminate between fentanyl (0.04 mg/kg) and saline in a two-lever procedure. Using a FR 10 schedule of food reinforcement, drug-induced differences between the number of reinforcers obtained under fentanyl and saline conditions were observed. The effect of eliminating these differences on the outcome of generalization tests was investigated by different manipulations. In one group (N=10), the FR 10 schedule used during saline sessions was changed to FR 6 during drug sessions. In a second group (N=12), saline sessions ended after the number of reinforcers obtained was equal to the number obtained during the preceding drug session. A control group (N=10) was trained using a FR 10 schedule under both conditions. Elimination of differences in reinforcement frequency 1) accelerated the acquisition of the discrimination, 2) diminished response bias, 3) flattened the slope and reduced the ED50 value of generalization gradients of fentanyl, morphine and sufentanil and 4) increased the ED50 value of naloxone in antagonizing 0.04 mg/kg fentanyl. It is concluded that the unconditioned effects of 0.04 mg/kg fentanyl on response rate in a FR 10 procedure lead to differences between saline and drug sessions which contribute to the apparent discriminative stimulus properties of fentanyl.
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  • 170
    ISSN: 1432-2072
    Schlagwort(e): β-Carbolines ; Drug discrimination ; Benzodiazepine ; Diazepam ; Chlordiazepoxide ; Pentylenetetrazol ; Anxiety ; FG 7142 ; ZK 93423 ; ZK 91 296 ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The discriminative stimulus properties of three β-carboline derivatives were studied in three groups of rats trained, respectively, to discriminate diazepam (2.5 mg/kg IP), chlordiazepoxide (CDP, 5 mg/kg IP) or pentylenetetrazol (PTZ, 15 mg/kg IP) from saline in standard procedures employing two-lever operant chambers. Two β-carbolines, ZK 91296 and ZK 93423, substituted for the benzodiazepines in both CDP- and diazepam-trained rats. The neutral benzodiazepine antagonist Ro 15-1788 blocked the diazepam discriminative stimulus and the ability of ZK 91296 to substitute for diazepam. A third β-carboline, FG 7142, was not identified as benzodiazepine-like in generalization tests in either diazepam- or CDP-trained rats, but when administered together with CDP antagonized the benzodiazepine discriminative stimulus. In rats trained to discriminate PTZ from saline (a discrimination which is thought to depend on the anxiogenic properties of PTZ) the PTZ cue was antagonized by diazepam and ZK 93423, and partially antagonized by ZK 91296. The PTZ cue generalized to FG 7142 and this generalization was partially antagonized by Ro 15-1788. These results suggest that the three β-carbolines provide more than one kind of discriminative stimulus, consistent with the classification of ZK 93423 as an agonist at central benzodiazepine receptors, with ZK 91 296 as a partial agonist, and with FG 7142 as an inverse agonist. Pharmacologically, ZK 93 423 and ZK 91 296 may exhibit anxiolytic qualities, whereas FG 7142 produces anxiogenic effects.
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  • 171
    ISSN: 1432-2072
    Schlagwort(e): Benzodiazepine receptors ; β-Carboline-3-carboxylates ; Anxiety ; Epilepsy ; Ataxia ; Rat ; Mouse
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract ZK 91296 (ethyl 5-benzyloxy-4-methoxymethyl-β-carboline-3-carboxylate) is a potent and selective ligand for benzodiazepine (BZ) receptors. Biochemical investigations indicate that ZK 91296 may be a partial agonist at BZ receptors. Such partial agonism may explain to some extent why ZK 91296 needs higher BZ receptor occupancy than diazepam for the same effect against chemical convulsants and for behavioural effects. The lack of sedatiye effects, and the very potent inhibition of reflex epilepsy, spontaneous epilepsy and DMCM-induced seizures suggest, furthermore, that ZK 91296 may possess pharmacological selectivity for a particular type of BZ receptor interaction, perhaps including topographic as well as receptor subtype differentiation.
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  • 172
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 83 (1984), S. 367-372 
    ISSN: 1432-2072
    Schlagwort(e): GABA ; Mouse-killing ; Aggressive behaviour ; GVG ; DPA ; THIP ; Picrotoxin ; Bicuculline ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract When GABA-potentiating compounds were administered IP to rats with prior experience of mouse-killing behaviour, a reduction of killing was observed with gammavinyl GABA (200 and 400 mg/kg) and nipecotic acid amide (400 mg/kg), while no significant effect was noted following injection of dipropylacetate or THIP. The inhibitory effects of gamma-vinyl GABA and nipecotic acid amide were not reversed by subsequent injection of picrotoxin and were associated with sedation as observed in open field and actograph tests. When GABA-potentiating compounds were administered to food-deprived rats exposed for the first time to a mouse (initial elicitation), administration of gamma-vinyl GABA, dipropylacetate, nipecotic acid amide or THIP increased the incidence of mouse-killing behaviour. Conversely, the incidence of mouse-killing under the same conditions was reduced following injections of picrotoxin. These results do not support the hypothesis that the general activation of GABAergic mechanisms inhibits mouse-killing behaviour in rats. On the contrary, data obtained in naive animals suggest that potentiation of these mechanisms actually facilitates the initial elicitation of this behaviour.
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  • 173
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 84 (1984), S. 109-114 
    ISSN: 1432-2072
    Schlagwort(e): Intracranial self-stimulation ; Brain stimulation reward ; Shuttle box ; Nicotine ; d-Amphetamine ; Chronic administration ; Tolerance ; Motor performance ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rats were permitted to turn on and off electrical stimulation of the medial forebrain bundle, by alternating between two photobeams running along opposite walls of a shuttle box. Entry into one beam (the “ON” beam) triggered the delivery of a succession of short, regularly occurring (1 Hz) pulse trains, which could be terminated by breaking the other (“OFF” beam). The two beams were frequently reversed. When this occurred, the rat was given a free period of 10 s in which to reorient, and brain stimulation reward was then assessed by the amount of time spent receiving brain stimulation (SST) within a fixed interval of time. SST increased with increasing current intensity. After training, subjects were tested for 10 consecutive days, alternately with saline and nicotine bitartrate (0.4 mg/kg SC base), and received a constant daily dose of the drug (0.4 mg/kg). Initially, nicotine visibly impaired motor performance for several minutes after injection, which may at least partly explain the observed reduction of SST; both effects waned across successive nicotine tests. Later in each 78 min session, nicotine consistently increased SST over a range of current, and drugged subjects entered the photobeams more frequently even when electrical stimulation was unavailable. d-Amphetamine sulphate (0.25, 0.75 mg/kg SC salt), given 15 min before testing, also increased SST and stimulated responding. The possible effects of motor impairment or activation on SST are discussed, and it is concluded that nicotine and d-amphetamine may have enhanced the rewarding properties of medial forebrain bundle stimulation.
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  • 174
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 84 (1984), S. 285-286 
    ISSN: 1432-2072
    Schlagwort(e): Caffeine ; Tolerance ; Perinatal treatment ; Locomotor activity ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Pregnant rats were treated with caffeine in their drinking water at doses of 136.3 mg/kg/day during gestation and 222.2 mg/kg/day during lactation. The resulting off-spring at 60 days of age (40 days after drug withdrawal) were tested in an activity monitor cage. Spontaneous locomotor activity and that induced by caffeine (10, 30, 60 mg/kg/day) were observed. Treated rats showed apparent tolerance to caffeine-induced motility. Therefore perinatal caffeine treatment seems to induce long-lasting tolerance. This finding contrasts with those previously reported for chronic caffeine treatment in adult rats, where tolerance disappears after only 2–3 weeks following drug with-drawal.
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  • 175
    ISSN: 1432-2072
    Schlagwort(e): Sulpiride isomers ; Imipramine ; Desipramine ; Haloperidol ; Apomorphine ; Hypomotility ; Hypothermia ; Behavioural despair ; Learned helplessness ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The atypical neuroleptic sulpiride is also prescribed for depression because of its activating effect. However, such an effect does not necessarily imply an action identical to that of classical antidepressants, and a laboratory comparison of the neuroleptic and antidepressant activities of sulpiride may contribute to a better definition of its psychotherapeutic profile. Sulpiride isomers were studied in the rat in four behavioural models of depression which are thought to be influenced by neuroleptics in different ways. Desipramine (imipramine) and haloperidol were employed in each test as a standard antidepressant and neuroleptic, respectively. The four tests were: 1) prevention of apomorphine-induced sedation: 2) antagonism of apomorphine-induced hypothermia; 3) behavioural despair (swim test); 4) learned helplessness (FR2 lever pressing escape). Desipramine ameliorated behaviour in all tests; haloperidol ameliorated the response to test 1, influenced that to test 2 in a neuroleptic-like way and worsened the responses to tests 3 and 4.(-)-Sulpiride worked in a similar way to haloperidol in all tests.(+)-Sulpiride significantly and dose-dependently ameliorated the responses to test 3 and was inactive in the others. No conclusion was drawn from test 1 owing to its lack of specificity; the results of the remaining tests indicated a neuroleptic profile of (-)-sulpiride and suggested a potential “antidepressant” activity of (+)-sulpiride which merits further investigation.
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  • 176
    ISSN: 1432-2072
    Schlagwort(e): Saccharin intake ; Pain threshold ; Diabetes ; Streptozotocin ; Morphine tolerance ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rats of the LC-2-HI strain, selected for high rates of self-stimulation, were supplied with a 3 mM saccharin solution. Within 1 week they developed markedly prolonged latencies to painful stimuli on a hot-plate. In contrast, a similar effect became manifest in LC-2-LO rats only after 3 weeks. Both strains of rats were made diabetic by injection of streptozotocin. LO rats showed more polydipsia and hyperglycemia than HI rats and, when drinking saccharin solution, developed cross-tolerance to morphine within about 2 weeks. It is assumed that saccharin consumption stimulates the release of endogenous opioid peptides, probably via stimulation of gustatory sweet receptors. The opioid peptides exert a biphasic effect: initially they raise the pain threshold, but at a later stage they cause chronic crosstolerance to morphine.
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  • 177
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 82 (1984), S. 327-329 
    ISSN: 1432-2072
    Schlagwort(e): Reserpine ; Dextroamphetamine ; Stereotypy ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The augmentation of the rat stereotypy response with repeated amphetamine doses, put forward as a model of human amphetamine psychosis, was examined during concurrent reserpinization. The effects of reserpinization, amphetamine treatment, and amphetamine dose on four dependent variables representing the time course of stereotypy ratings after a post-treatment amphtamine dose, were tested by three-way MANOVA. An earlier onset of stereotypy, as occurred in nonreserpinized rats, was not detected in reserpinized rats, but an earlier offset of stereotypy with repeated amphetamine occurred in these rats when high amphetamine doses were used.
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  • 178
    ISSN: 1432-2072
    Schlagwort(e): Supersensitivity ; 5-HT1 receptors ; Methysergide ; Ketanserin ; Pirenperone ; 5-HT agonist rotational behaviour ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The rotational behaviour induced by 5-HT agonists has been investigated in rats with lesions of the dorsal raphe' nucleus (DRN). We have previously reported that 5-methyoxy-N,N-dimethyl-tryptamine (5-MeODMT) caused dose-related contralateral rotation in rats with 5,7-dihydroxytryptamine (5,7-DHT) lesions of the DRN. Similar findings are now presented for the 5-HT1 agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-methoxy-3 (1,2,3,6-tetrahydropyridin-4-yl) (1H indole) (RU24969). In this model, in agreement with the behavioural studies, both agonists were shown to have a greater affinity for the 5-HT1 binding site when compared with the 5-HT2 binding site. Antagonist studies using selective 5-HT2 antagonists (ketanserin and pirenperone) at non-sedative doses failed to inhibit this behaviour. In contrast, the classical 5-HT antagonist methysergide caused significant inhibition of the rotational behaviour. These results suggest that 5-HT agonist-induced rotation in the rat is mediated via 5-HT1 receptors, probably located in the substantia nigra.
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  • 179
    ISSN: 1432-2072
    Schlagwort(e): Catecholamines ; Cerebroventricular perfusion ; Carbamazepine ; Imipramine ; Desmethylimipramine ; Tranylcypromine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Concentrations of endogenous norepinephrine, dopamine and epinephrine in cerebroventricular perfusates were used to evaluate the effects of drugs on the availability of extracellular catecholamines in the intact rat brain. Administration of the antidepressant drugs imipramine, desmethylimipramine or tranylcypromine resulted in marked increases of both norepinephrine and dopamine concentrations while epinephrine levels were not affected. Treatment with a similar dose of carbamazepine — an anticonvulsant drug with antidepressant activity — resulted in a significant increase in dopamine concentrations without apparent effect on either norepinephrine or epinephrine. It is suggested that at the applied dose, carbamazepine may act to modify the uptake, release or metabolism of dopamine in brain areas adjacent to the cerebroventricular space without affecting the other catecholamines.
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  • 180
    Digitale Medien
    Digitale Medien
    Springer
    Journal of cancer research and clinical oncology 108 (1984), S. 56-59 
    ISSN: 1432-1335
    Schlagwort(e): DNA methylation ; Rat ; Procarbazine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The cytostatic drug procarbazine has previously been shown to be a potent transplacental neurotropic carcinogen in rats. Following a single IP administration of (14C-methylprocarbazine (110 mg/kg) on day 22 of gestation, methylation products with cellular DNA were determined in fetal and maternal rat organs. The concentration of the major adduct N7-methylguanine was highest in the maternal liver (224 μmol/mol guanine). Fetal and nonhepatic maternal tissues exhibited significantly lower levels, but differed little from each other. In brain, lung, intestines, and placenta the O 6-methylguanine/N7-methylguanine ratio was close to 0.11, indicating that procarbazine, like other methylating carcinogens, initiates malignant transformation via methyldiazonium hydroxide as the ultimate reactant. Following a single dose of (14C-methyl)procarbazine to newborn animals, methylpurine values were 30–60 times lower than after prenatal administration. This suggests that DNA alkylation in nonhepatic tissues occurs by systemic distribution of a proximate carcinogen formed in the adult rat liver.
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  • 181
    Digitale Medien
    Digitale Medien
    Springer
    Journal of cancer research and clinical oncology 108 (1984), S. 114-120 
    ISSN: 1432-1335
    Schlagwort(e): Nasal cavities ; Rat ; DOPN
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Weekly SC administration of 2,2-dioxopropylnitosamine to 88 Sprague-Dawley rats resulted in the induction of 76 separate neoplasms in the respiratory region of the nasal cavities. No tumors of the olfactory region were found. Histologically there were 37 squamous papillomas, 17 transitional papillomas, and 22 squamous cell carcinomas. These tumors were compared with a selected group of 53 related human tumors of the nasal and paranasal cavities, consisting of 11 squamous cell papillomas, 13 transitional papillomas, and 29 squamous cell carcinomas. While the experimental squamous cell papillomas showed a striking histological resemblance with the squamous papillomas observed in man, none of the experimental transitional papillomas had evidence of the characteristics inverted pattern seen in humans: nevertheless, the experimental tumors showed signs of incomplete squamous metaplasia and preservation of intraepithelial secretory glands, features commonly seen in transitional papillomas of man. The squamous cell carcinomas of this experiment were very similar to the corresponding human tumors in morphology and sex incidence. In both species a significant number of squamous cell carcinomas were keretinizing and of a high grade of histological malignancy. In addition, 69% of the human squamous cell carcinomas occurred in the male sex, and 72% of the experimental carcinomas developed in males. This comparative study suggests that further studies investigating the significance of nitrosamines as suspected etiologic factors of nasal carcinogenesis in man may be useful.
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  • 182
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 413-436 
    ISSN: 1573-8744
    Schlagwort(e): methylene chloride ; pharmacokinetics ; physiological model ; hybrid model ; I.V. administrations ; mice
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract A physiologic mathematical model was developed to describe the time course of14C-methylene chloride (14CH2Cl2) distribution and elimination in mice following single i.v. administrations of 10 and 50mg/kg. A whole-body model was used to simulate14CH2Cl2 concentrations in blood and tissues, pulmonary clearance of unchanged14CH2Cl2, and metabolic conversion to14CO2 and14CO as monitored by the appearances of these metabolites in expired breath. This diffusion-limited model was identified via a sequential optimization scheme using hybrid models for each compartment. Pulmonary elimination of unchanged14CH2Cl2 was modeled as a linear process while hepatic metabolism of14CH2Cl2 to the compounds14CO2and14CO was described by a saturable metabolic rate term. The model adequately described the dose dependence in methylene chloride distribution and metabolism when simulations were compared to experimental data.
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  • 183
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 451-461 
    ISSN: 1573-8744
    Schlagwort(e): rabbit ear chamber ; granulation tissue ; serum albumin ; sodium fluorescein ; Stokes-Einstein radius ; fluorescence ; photometric analysis ; vascular permeability ; renal clearance ; erythrocyte-free plasma layer ; two-compartment model ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Plasma pharmacokinetics of sodium fluorescein, fluorescein isothiocyanate conjugated bovine serum albumin, and a graded series of dextrans of 19,400 to 71,800 MW were monitored continuously using a noninvasive photometric technique in individual blood vessels of tissue grown in a rabbit ear chamber. The data obtained were fitted with a two-compartment open model to obtain an effective permeability and an effective clearance. Both parameters decreased with increasing molecular radius for dextrans. Values for albumin were considerably less than expected on the basis of molecular radius, presumably due to the configuration, charge, and binding characteristics of albumin.
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  • 184
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 351-365 
    ISSN: 1573-8744
    Schlagwort(e): pharmacokinetics ; model discrimination ; experiment design ; information theory
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The need for objective design of pharmacokinetic experiments aimed at model discrimination is argued. A sequential design strategy based on information theory is outlined. The characteristics of this strategy and its applicability to pharmacokinetic experiments is examined by means of computer simulated experiments. The limitations of the technique are discussed and alternative approaches outlined.
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  • 185
    Digitale Medien
    Digitale Medien
    Springer
    Acta neuropathologica 63 (1984), S. 57-65 
    ISSN: 1432-0533
    Schlagwort(e): Fetal alcohol syndrome ; Rat ; Cerebellum ; Purkinje cells ; Synaptic maturation ; Metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Fetal alcohol syndrome was produced in rats by feeding an ethanol-enriched, vitamine-supplemented liquid diet over a period of 4 weeks before mating and throughout pregnancy. The amount of ethanol was equivalent to 38–40% of the daily calories; control animals were fed an isocaloric amount of sucrose. The offspring of experimental animals displayed a diminished birth weight. In contrast to previous experiments, the ethanol diet was also administered during the lactating period. On postnatal day 7, experimental animals and controls were killed by perfusion and the cerebella prepared for electron microscopy. Morphometric analysis showed a reduced number of Purkinje cells. On day 12, Purkinje cells of experimental animals displayed ultrastructurally fewer organelles. Furthermore, a delayed synaptogenesis in the molecular layer was demonstrated with osmiumzinc iodide and ethanolic phosphotungstic acid showing an immature appearance of the presynaptic grid and weaker stained synaptic cleft material. The following discussion deals with possible mechanisms underlying these alcohol-induced alterations of cerebellar synaptogenesis.
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  • 186
    Digitale Medien
    Digitale Medien
    Springer
    Acta neuropathologica 64 (1984), S. 192-202 
    ISSN: 1432-0533
    Schlagwort(e): Astrocytoma ; Blood-brain barrier ; HVEM ; Transendothelial channels ; Protein tracer ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Brain tumors, benign and malignant, are characteristically more permeable to various types of tracer molecules than the neuropil in which they are embedded. Impermeability of brain neuropil capillaries is imparted by the blood-brain barrier, the anatomic basis of which is the network of interendothelial zonulae occludentes that seal capillary endothelial cells. To explore both the vascular elements of brain neoplasms and the route of tracer extravasation from them, as well as the possible effects of brain tumors on the permeability of peritumoral neuropil capillaries, brain tumors were induced in newborn Wistar rats by intracerebral (i.c.) injection of C-6 astrocytoma cells. The protein tracer horseradish peroxidase (HRP) was injected systemically into both normal and tumorbearing rats to mark the pathway along which it flowed into the tumor parenchyma tissue spaces, and to signal any concomitant tracer loss from the tumor extracellular compartment or peritumoral brain capillaries, into the neuropil extracellular milieu. Electron-microscopic examination on thin plastic sections of tumor and peritumoral neuropil revealed massive extravasation of tracer into the tumor tissue spaces, but none was seen outside of the capillaries in the surrounding brain neuropil. Zonulae occludentes of both tumor capillary endothelium and brain capillary endothelium were devoid of tracer and judged tight (sealed). Tracer was seen in pinocytotic vesicles in the highly attenuated endothelium of tumor capillaries and also in cytoplasmic vesicles within the tumor cells. The peritumoral and contralateral neuropil capillary endothelium exhibited reaction product-filled pinocytotic vesicles and vesiculo-tubular conduits. Often, one end of a HRP-filled vesiculo-tubular channel appeared continuous with either the luminal or abluminal plasmalemma. High-voltage electron microscopy of these conduits often showed them to be continuous with both luminal and abluminal surfaces of the endothelium, thus forming a continuum across the capillary wall. In addition, these transendothelial channels, clearly constituted as chains of fused vesicles, were often seen in close proximity to, or fused with, dense bodies in the endothelial cytoplasm. In spite of the presence of HRP-filled structures in the peritumoral neuropil capillary endothelium of tumor-bearing rats, no evidence of tracer extravasation from these vessels was apparent. These results suggest that although peritumoral and contralateral neuropil capillaries possess the machinery for extravasation of tracer, likely as a response to the presence of the neoplasm, tracer is not lost but, instead, is degraded by endothelial enzymes. The extensive flooding of the tumor extracellular compartment with tracer may be achieved by transport of HRP across the very thin walls of tumor capillaries by single cytoplasmic vesicles which structurally and functionally play the role of transendothelial channels. Based on the results of this study, it is unlikely that molecules delivered systemically to treat brain neoplasms, will leak into the peritumor or contralateral neuropil, either from their own capillaries, or from the extracellular compartment of the tumor parenchyma.
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  • 187
    Digitale Medien
    Digitale Medien
    Springer
    Acta neuropathologica 62 (1984), S. 276-283 
    ISSN: 1432-0533
    Schlagwort(e): Rat ; Brain ; Lead intoxication ; Protein deprivation ; Growth and development
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Most studies on lead toxicity in the suckling rat have been performed with doses leading to growth retardation. In a previous paper (Sundström et al. 1983), the effects of different lead doses on normal suckling rats were described. The dose of 10 mg/kg body weight daily given on days 1–15 pp produced minute hemorrhagic lesions on day 15 in the cerebellum, whereas rats given 5 mg/kg body weight daily lacked microscopically discernible pathologic changes in the brain. None of these groups exhibited growth retardation. To further elucidate the association between lead encephalopathy and malnutrition, lead was administered to protein-deprived suckling rats. Protein deprivation was achieved by a diet with 50% reduction of protein content. The móthers of the pups were fed this diet from 2 weeks before conception throughout the experiment. Experimental animals were injected i.p. with 5 mg or 10 mg lead nitrate/kg b.wt. daily. Littermates, injected with vehicle without lead nitrate served as controls. Protein-deprived rats without either treatment were “external” controls. Animals were killed at 10, 15, and 20 days age for determination of lead content in blood and brain and for light-microscopic examination. The protein-deprived rats given 10 mg/kg b.wt. daily were growth-retarded as compared to unexposed protein-deprived rats. The mortality was almost 100% at 15–20 days pp. At 15 days, the cerebellum of these rats showed abundant hemorrhages, and the cerebrum was also hemorrhagically discolored. Protein-deprived rats given 5 mg/kg b.wt. daily did not differ significantly from unexposed protein-deprived rats with regard to body weight gain. They presented a mortality of about 20% on days 15–20. At 15 days, cerebellar hemorrhages were a regular finding, though not as devastating as in the animals given 10 mg lead nitrate/kg b.wt. daily. The results imply an increased vulnerability to lead in protein-deprived rats as compared to normal rats. The severe encephalopathy in protein-deprived rats was associated with higher blood lead levels than in normal rats exposed to an equivalent lead burden.
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  • 188
    Digitale Medien
    Digitale Medien
    Springer
    Acta neuropathologica 64 (1984), S. 139-147 
    ISSN: 1432-0533
    Schlagwort(e): Cerebral ischemia ; Cell death ; Endoplasmic reticulum ; Hippocampus ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary An unusual, slowly progressing neuronal damage has been reported to occur in the gerbil hippocampus following ischemia (Kirino 1982). Delayed neuronal death following ischemia has also been noticed in the rat four-vessel occlusion model (Pulsinelli et al. 1982). By light microscopy this slow neuronal injury in the rat was not different from the previously known neuronal ischemic cell change. This report lead us to the question as to whether neurons in the rat hippocampus are damaged rapidly following an initial latent period or deteriorate slowly and progressively until they display overt changes. To clarify this point, observation was done on the hippocampal CA1 sector of the rat following ischemia. Rats were subjected to four-vessel occlusion, and those which developed ischemic symptoms were perfusion-fixed. Although the change appeared very slowly and lacked microvacuolation of the cytoplasm, neuronal alteration was practically not different from classical ischemic cell change. By electron microscopy, however, the change was detectable when the neurons still appeared intact by light microscopy. An increase in the membranous organelles and deposition of dark substances were the initial manifestations. It seemed that the CA1 neurons deteriorated very slowly and progressively, and that they retained partial viability in the initial phase of the change. In spite of the difference in light-microscopic findings, the mechanisms underlying delayed neuronal death in the rat and gerbil hippocampus seemed to be identical.
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  • 189
    Digitale Medien
    Digitale Medien
    Springer
    Bulletin of experimental biology and medicine 98 (1984), S. 1183-1185 
    ISSN: 1573-8221
    Schlagwort(e): ethanol ; pharmacokinetics ; blood ; serotonin ; dopamine ; noradrenalin ; brain ; CBA and C57Bl/6 mice
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
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  • 190
    Digitale Medien
    Digitale Medien
    Springer
    Bulletin of experimental biology and medicine 98 (1984), S. 1226-1227 
    ISSN: 1573-8221
    Schlagwort(e): pharmacokinetics ; alcohol ; isolation ; stress
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
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  • 191
    Digitale Medien
    Digitale Medien
    Springer
    Journal of chemical ecology 10 (1984), S. 1007-1018 
    ISSN: 1573-1561
    Schlagwort(e): Rat ; Rattus norvegicus sp. ; odorants ; stress ; behavior ; open field ; corticosterone ; fox dropping ; ketone ; sulfur ; compounds ; tans ; mercaptoketones ; repellent ; structure-activity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract The stress for 12 sulfur-containing synthetized volatiles was evaluated in male Wistar rats and compared to that for fox-dropping extract concentrate. Stress behavior was analyzed by quantifying various stress responses in a standard open field and measuring the increase in plasma corticosterone concentration. Nine compounds induced stress—a dihydrothiazole, two cyclic polysulfides, five mercaptoketones, and a mercaptan. For the mercaptoketones, the following structure-activity relationships were observed. Size can vary considerably; the mercapto group can be either alpha or beta and either secondary or tertiary. The keto group is not essential, since a structurally related mercaptan remains active. The mercapto group is essential for activity in mercaptoketones, since conversion to a methyl sulfide resulted in a neutral response. This type of odorant could function as an allomone and may have potential in rat control as an area repellent.
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  • 192
    ISSN: 1435-2451
    Schlagwort(e): Hyperthermia ; Induced colonic carcinoma ; Rat ; Chemotherapy ; BCNU ; Ftorafur
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Hyperthermie zur Behandlung von Tumoren wird seit längerem in In-vitro- und In-vivo-Versuchen und auch in der Klinik in verschiedenen Anwendungsformen erprobt. Bei der Kombination von Hyperthermie mit Chemotherapie wird eine überadditive cytostatische Wirkung beschrieben. In einem klinisch orientierten, kontrolliert durchgeführten Tierversuch wurde an einem durch N-Nitrosoacetoxymethylmethylamin (AMMN) induzierten autochthonen Coloncarcinom bei Sprague-Dawley-Ratten eine lokale, moderate Hyperthermie (43,5°C, 3 × 60 min) und eine Kombinationsbehandlung von Hyperthermie und Polychemotherapie (BCNU und Ftorafur) durchgeführt unter endoskopischer Diagnosestellung und Verlaufskontrolle. Es konnte keine Überlebenszeitverlängerung durch die angewendeten Therapien und keine additive Wirkung der lokalen moderaten Hyperthermie in Kombination mit der Chemotherapie bei diesem „harten”, d. h. relativ chemotherapieresistenten, Tumormodell gesehen werden.
    Notizen: Summary The use of hyperthermia for the treatment of tumors has been tested in in vitro and in vivo experiments as well as clinically for a long time. Combination of hyperthermia with chemotherapy was reported to result in overadditive cytostatic effects. In a clinically adapted, controlled animal experiment, local moderate hyperthermia (43.5°C, 3 × 60 min) alone and in combination with polychemotherapy (BCNU and Ftorafur) was used for the treatment of AMMN-(N-nitrosoacetoxymethyl-methylamine) induced autochthonous colonic carcinomas in Sprague-Dawley rats. Diagnosis and follow-up inspections were carried out endoscopically. The applied therapies did not result in prolonged survival times, nor was an additive effect seen after combined hyperthermia and chemotherapy in this “hard”, i. e. relatively chemotherapy-resistent, tumor model.
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  • 193
    ISSN: 1435-2451
    Schlagwort(e): Hyperthermia ; Yoshida sarcoma ; Chemotherapy ; BCNU ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Hyperthermie zur Cytostase von Malignomen ist in zahlreichen In-vitro- und In-vivo-Untersuchungen beschrieben worden. Die Kombination von Chemotherapie mit Hyperthermie soll zur Potenzierung der therapeutischen Wirkung führen. Ein Forschungsgegenstand ist der zeitliche Abstand zwischen beiden Therapiemodalitäten. Anhand eines Yoshida-ColonModells bei Sprague-Dawley-Ratten wurde eine lokale Hyperthermie (43°C, 60 min) im Abstand von 0, 3, 6, 9, 12 und 24 h nach einer Chemotherapie mit BCNU durchgeführt. Die Ergebnisse zeigten keine signifikante Steigerung der Heilungsrate durch die Hyperthermie. Angesichts unserer Ergebnisse sollten z.B. die mit groben Hoffnungen propagierten hyperthermen Peritoneallavagen erst im Tierexperiment einer kontrollierten Untersuchung unterzogen werden.
    Notizen: Summary There are numerous reports on in vitro and in vivo investigations of hyperthermia for cytostasis of malignant tumors. Combination of chemotherapy and hyperthermia is to potentiate the therapeutic effect. The time interval between the two types of therapy was the main subject of the present investigation. Local hyperthermia (43°C, 60 min) following BCNU chemotherapy at intervals of 0, 3, 6, 9, 12, and 24 h, respectively, was studied in a colonic Yoshida sarcoma model in Sprague-Dawley rats. No significant increase in the curing rate resulted from hyperthermic treatment. The results suggest that the highly anticipated hyperthermic peritoneal lavages should be investigated in controlled animal experiments prior to clinical use.
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  • 194
    Digitale Medien
    Digitale Medien
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    European journal of applied physiology 52 (1984), S. 235-242 
    ISSN: 1439-6327
    Schlagwort(e): Collagen ; Fast and slow twitch fibres ; Skeletal muscle ; Rat ; Endurance training
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The appearance of collagen around individual fast twitch (FT) and slow twitch (ST) muscle fibres was investigated in skeletal muscles with different contractile properties using endurance trained and untrained rats as experimental animals. The collagenous connective tissue was analyzed by measuring hydroxyproline biochemically and by staining collagenous material histochemically in M. soleus (MS), M. rectus femoris (MRF), and M. gastrocnemius (MG). The concentration of hydroxyproline in the ST fibres dissected from MS (2.72±0.35 Μg·mg−1 d.w.) was significantly higher than that of the FT fibres dissected from MRF (1.52±0.33 Μg·mg−1 d.w.). Similarly, the concentration of hydroxyproline was higher in ST (2.54±0.51 ⧎g·mg−1 d.w.) than in FT fibres (1.60±0.43 Μg·mg−1 d.w.), when the fibres were dissected from the same muscle, MG. Histochemical staining of collagenous material agreed with the biochemical evidence that MS and the slow twitch area of MG are more collagenous than MRF and the fast twitch area of MG both at the level of perimysium and endomysium. The variables were not affected by endurance training. When discussing the role of collagen in the function of skeletal muscle it is suggested that the different functional demands of different skeletal muscles are also reflected in the structure of intramuscular connective tissue, even at the level of endomysial collagen. It is supposed that the known differences in the elastic properties of fast tetanic muscle compared to slow tonic muscle as, e.g., the higher compliance of fast muscle could at least partly be explained in terms of the amount, type, and structure of intramuscular collagen.
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  • 195
    ISSN: 1590-3478
    Schlagwort(e): Anticonvulsants ; phenytoin ; pharmacokinetics ; Michaelis-Menten kinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Sommario Il metodo di Mullen e Foster è stato applicato al fine di individualizzare la posologia della fenitoina in 24 pazienti epilettici. Le caratteristiche di precisione ed affidabilità del metodo sono state valutate confrontando le concentrazioni plasmatiche previste con quelle misurate sperimentalmente. La differenza percentuale tra valori e misurati della concentrazione plasmatica di fenitoina è risultata inferiore al 15 per cento in 22 casi su 35 (63 per cento), compresa tra il 15 e il 25 per cento in 8 casi su 35 (23 per cento), superiore al 25 per cento in 6 casi su 35 (17 per cento).
    Notizen: Abstract The Mullen and Foster method was prospectively applied for individualizing phenytoin dosage in 24 epileptic patients. Accuracy and reliability of the method were assessed by comparing predicted and measured values of plasma phenytoin steady-state concentration. The absolute difference between predicted and measured phenytoin levels was less than 15 percent in 22 of 35 cases (63 percent), between 15 and 25 percent in 8 of 35 cases (23 percent) and more than 25 percent in 6 of 35 cases (17 percent).
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  • 196
    ISSN: 1432-0878
    Schlagwort(e): Caldesmon ; Actin ; Immunocytochemistry ; Small intestine ; Smooth muscle ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The distribution of caldesmon (a calmodulin-binding, F-actin-interacting protein) (Sobue et al. 1982) and of actin was studied in the rat's small intestine by means of light-microscopic immunocytochemistry. Positive immunostaining for caldesmon was seen in smooth muscle cells of the intestinal wall, and of blood vessels, and in the apical portion of the absorptive epithelial cells. The immunoreactivity in goblet cells was difficult to recognize. The positive reaction to immunostaining for actin showed almost the same pattern as that for caldesmon. These results suggest that this calmodulin-binding protein may play an important role in the control of actin-myosin interaction in smooth muscle cells and in non-muscle cells.
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  • 197
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 235 (1984), S. 485-489 
    ISSN: 1432-0878
    Schlagwort(e): Ventromedial nucleus ; Hypothalamus ; Ultra-structure ; Nucleoli ; Estrogen effects ; Chromatin ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Estrogen is accumulated from the blood by nerve cells in the ventromedial nucleus of the hypothalamus and can facilitate female reproductive behavior by acting on this region of the brain. This cell group was examined in ovariectomized female rats, given estrogen or control treatment, by use of light and electron microscopy. A significantly greater portion of the nerve cells in the estrogen-treated animals had protuberances on their nucleolar surfaces, apparent under the light microscope. The fine structure of such protuberances included dense, aggregated material, which is shown to contain DNA by the sodium tungstate staining technique. Because increased numbers of such protuberances were found in nuclei of cells of the experimental group where previous studies demonstrated a significant increase in ultrastructural signs of biosynthetic activity, they may be associated with increased RNA synthesis. Thus, they could indicate, ultrastructurally, increased synthetic rates for RNA in nerve cells through which estrogen promotes reproductive behavior.
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  • 198
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 235 (1984), S. 669-673 
    ISSN: 1432-0878
    Schlagwort(e): Liver-cell heterogeneity ; Hepatic venous branches ; Karyometry ; Binucleate cells ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary In untreated adult male albino rats nuclear volume and the percentage of binucleate cells were determined in the first layer of hepatocytes adjacent to hepatic venous branches of varying diameters (〈40 μm, 40 μm–80 μm, 80 μm–120μm, 120 μm–160 μm, 〉160 μm), and in the third and fourth layer of hepatocytes in the remainder of the perivenous parenchyma. In the first layer of hepatocytes adjacent to the vascular structures means of nuclear volume are significantly lower and percentage of binucleate cells significantly higher than in the cells of the remainder of the perivenous parenchyma. Within each area measured distribution curves of nuclear volume classes were homogeneous but showed heterogeneity in comparison with each other. The morphometric data presented in this study strongly support the opinion of the heterogeneity of liver cells in the perivenous zone, as previously postulated on the basis of histochemical investigations.
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  • 199
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 236 (1984), S. 305-315 
    ISSN: 1432-0878
    Schlagwort(e): Hepatocytes ; Rat ; Liver ; Circadian rhythm ; Morphometry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Subcellular structures of hepatocytes in periportal and perivenous zones were examined during 24 h. The volume, surface and numerical profile densities of cytoplasmic organelles were analysed morphometrically. Most subcellular structures in periportal and perivenous hepatocytes were subject to strong circadian variations. In hepatocytes from both zones, the volume densities of smooth endoplasmic reticulum (sER), mitochondria, lysosomes, peroxisomes, polysomes and lipid droplets demonstrated peak values at 16.00 h, 20.00 h or 00.00 h; trough values were at 04.00 h, 08.00 h, or 12.00 h, except for peroxisomes (16.00 h). However, the volume densities of glycogen granules and rough endoplasmic reticulum (rER) in periportal and perivenous hepatocytes exhibited maximal values at 04.00 h, 08.00 h or 12.00 h and minimal values at 20.00 h. The surface densities of sER, mitochondria, lysosomes and peroxisomes, and the numerical profile densities of mitochondria, lysosomes and peroxisomes in periportal and perivenous hepatocytes showed similar trends. These events suggest that membranes of the rER show a partial correlation with the sER, mitochondrial and lysosomal membranes during the 24-h span. This may involve the interaction between ribosomes and rER. Almost all cytoplasmic organelles examined displayed significant differences between periportal and perivenous hepatocytes, morphometrically and in fine structure, indicating that the morphofunctional variability of hepatocytes differs depending on the location in the liver acinus.
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  • 200
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 236 (1984), S. 321-325 
    ISSN: 1432-0878
    Schlagwort(e): Triiodothyronine ; Radioautography ; Mitochondria ; Liver ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary To assess the distribution of the thyroid hormone triiodothyronine (T3) within intact living cells, freshly prepared dispersed rat hepatocytes were incubated with [125I]-T3 for periods of 5 min and 30 min. Lightand electron-microscopic (EM) radioautography was carried out to determine the distribution of grains over the isolated cells. Both procedures showed the grains distributed almost entirely over the cytoplasmic matrix rather than the nucleus. Grain counts under the EM were compared with expectation based on established quantitative methods. Only the mitochondria showed obvious and statistically significant grain counts, whereas the nucleus failed to accumulate grains in excess of expectations by chance alone based on area. The findings support the existence of mitochondrial binding of T3, presumably a prerequisite for its action in direct stimulation of the mitochondria.
    Materialart: Digitale Medien
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