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Biomedical subjects

H Weber

Publications and source records attributed to H Weber.

At least 379 records · Page 21Linked to original sources
PubMed1985

Improvement of sporulation in the yeast Yarrowia lipolytica.

Strains of Yarrowia lipolytica forming exclusively spherical ascospores were developed through inbreeding. These strains are more suitable for micromanipulation than other inbred strains forming helm-shaped ascospores. External factors affecting sporulation frequency and tetrad formation in this yeast were investigated. Optimal formation of complete tetrads occurred at a narrow range of pH values around 6.0. Citrate was found to stimulate sporulation strongly. A synthetic medium containing citrate was developed to obtain standard conditions for maximum sporulation.

Ascomycota↗
PubMed1985

Toxic interaction of specific polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin: increased incidence of cleft palate in mice.

The induction of cleft palate in C57BL/6N mice is an extremely reproducible and sensitive indicator of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity. This endpoint was used to look for potential interactions between two polychlorinated biphenyl (PCB) congeners and TCDD. Both 2,3,4,5,3',4'-hexachlorobiphenyl (HCB) and 2,4,5,2',4',5'-HCB are of relatively low toxic potency, but their biological properties differ. Pregnant mice were treated with TCDD and either HCB on gestation Days 10 through 13, and the fetuses examined for the presence of cleft palate and renal abnormalities on gestation Day 18. At a dose of TCDD which caused a low level of cleft palate, moderate hydronephrosis was observed. No renal or palatal anomalies were detected after 2,4,5,2',4',5'-HCB treatment, and the combination of this isomer with TCDD had no effect on the incidence of TCDD-induced cleft palate. 2,3,4,5,3',4'-HCB caused mild renal toxicity, but no cleft palate. However, treatment of pregnant mice with a combination of TCDD and 2,3,4,5,3',4'-HCB resulted in a 10-fold increase in the incidence of cleft palate. Thus, the toxicity of compounds such as TCDD may be enhanced by compounds of relatively low acute toxicity such as selected PCBs. The widespread environmental occurrence of such combinations suggests a need for further evaluation of the mechanism of this interaction.

Abnormalities, Drug-Induced↗
PubMed1985

Teratogenic potency of TCDD, TCDF and TCDD-TCDF combinations in C57BL/6N mice.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and 2,3,7,8-tetrachlorodibenzofuran (TCDF) cause the same spectrum of fetal anomalies in C57BL/6N mice. Pregnant dams were treated with TCDD, TCDF and combinations of the 2 compounds on gestation day 10, and examined for maternal and fetal effects on day 18. The fetal kidneys were the most sensitive target for teratogenicity. The dose response for cleft palate induction fit the probit model for both compounds, suggesting that TCDD was approximately 30 times more potent than TCDF. The interaction between these 2 compounds was consistent with a model for additive toxicity.

Animals↗
PubMed1985

Adrenocortical cell function in the hypophysectomized domestic fowl: effects of growth hormone and 3,5,3'-triiodothyronine replacement.

The control of adrenocortical function in the domestic fowl (Gallus domesticus) was investigated using adrenocortical cells isolated from hypophysectomized (hypox) and intact cockerels and from hypox cockerels injected with T3, purified chicken GH (cGH), and T3 plus cGH. Corticosterone in plasma and cell incubations was measured by RIA. Cellular responses to varying concentrations of steroidogenic agents were fitted and statistically analyzed by computer. Hypophysectomy reduced the basal plasma corticosterone (B) concentration to 53% of the value in intact birds and eliminated a stress response. Although hypophysectomy reduced adrenal weight by 20%, it did not change relative adrenal weight (milligrams per 100 g BW). However, replacement with cGH increased relative adrenal weight by 24%, whereas replacement with T3 or T3 plus cGH reduced relative adrenal weight by 16%. In the absence of steroidogenic agents, there were no detectable differences in B production by adrenocortical cells isolated from various experimental groups. However, with a maximal steroidogenic concentration of ACTH, B production by isolated adrenocortical cells from hypox birds was 61% of that by cells from intact birds. The ED50 of ACTH for cells from hypox cockerels was 2.7 times greater than that of cells from intact cockerels, thus indicating a loss of cell sensitivity to ACTH after hypophysectomy (the greater the ED50, the lesser the cell sensitivity). Although cGH replacement increased maximal B production (Bmax) induced by ACTH to 329% that by cells from hypox cockerels, it increased the ACTH ED50 3.6 times, thus decreasing cell sensitivity more than hypophysectomy alone. In contrast to cGH, T3 replacement maintained the cell sensitivity to ACTH at the level of cells from intact birds, but lowered Bmax to 54% that of cells from hypox cockerels. The combination of cGH and T3 administered to hypox cockerels both maintained cell sensitivity to ACTH and raised the Bmax to 358% that of cells from hypox animals. These treatments also affected 8-bromo-cAMP-induced Bmax and pregnenolone-supported Bmax, but did not significantly alter the ED50 of these agents.(ABSTRACT TRUNCATED AT 400 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1985

Adrenocortical function in deoxycorticosterone acetate (DOCA)-hypertensive Yucatan miniature swine.

Adrenocortical function was assessed in six normal and six chronic (greater than 12 weeks), DOCA-hypertensive Yucatan miniature swine; mean arterial pressures were 115.3 +/- 11.7 and 163.6 +/- 27.2 mm Hg, respectively (mean +/- SEM). Adrenocortical function was evaluated in vivo by measuring changes in plasma cortisol and aldosterone in response to exogenous ACTH (0.25 mg, iv), and in vitro by measuring the responses of collagenase-isolated adrenocortical cells to ACTH and angiotensin II. Corticoids were measured by specific radioimmunoassay. Basal plasma cortisol values of conscious DOCA-hypertensive swine were approximately 53% of the values of normotensive swine (P less than 0.05). However, ACTH induced a 419% increase in plasma cortisol values in DOCA-hypertensive swine compared to a 261% increase in the normotensive swine (P less than 0.05). These differences between the two groups were not altered by anesthesia. There were no significant differences in ACTH-induced changes in plasma aldosterone between the normotensive and DOCA-hypertensive swine. Experiments in vitro showed that the corticoid secretory responses of adrenocortical cells from DOCA-hypertensive animals were 6 times more sensitive to ACTH and 3.2 times more sensitive to angiotensin II than those of cells from normotensive swine. Thus, despite the possibility of adrenocortical insufficiency due to suppressed plasma renin activity and the negative feedback of DOCA on the hypothalamic-hypophyseal-adrenal axis, adrenocortical function of DOCA-hypertensive swine was hyperresponsive to trophic hormones. Results from this study suggest that the DOCA-hypertensive swine may be a valuable model in elucidating the relationship between hypertension and adrenocortical function and in investigating nonclassical control of the adrenal cortex, that is, control exerted during the hypertensive state that exists apart from or in addition to that exerted by ACTH and angiotensin II.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1985

Aluminum-free oral phosphate binder.

For the purpose of intestinal phosphate binding we have developed aluminum free substances. These substances are natural polymers consisting of heteropolyuronic acid charged with different cations. The in vitro experiments showed an efficacy 2 to 3 times greater than Aludrox. During the clinical application, up to one year, no serious side effects have been detected. Serum phosphate levels could not be lowered in all patients to the desired level of 5 mg% mainly due to problems in patients compliance and to low dosage of the prescribed phosphate binder.

Administration, Oral↗
PubMed1985

Pharmacokinetics of nimodipine. I. Communication: absorption, concentration in plasma and excretion after single administration of [14C]nimodipine in rat, dog and monkey.

Studies on absorption, plasma concentrations and excretion with (+/-)isopropyl-2-methoxyethyl-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl) -3,5-pyridinedicarboxylate (nimodipine, Bay e 9736, Nimotop) have been conducted in rat, dog and monkey using the carbon-14-labelled substance and a wide range of doses (0.05-10 mg/kg) administered via different routes (intravenous, oral, intraduodenal). Nimodipine was well absorbed in all species. Peak plasma concentrations of radioactivity were determined 28-40 min (male rat), 60 min (female rat), about 3 h (dog) and 7 h (monkey) after administration. Dependent on the observation period (24-216 h) terminal half-lives for the elimination of radioactivity from plasma ranging between 4.6 h (female rat) and 157 h (dog) were observed. Comparing the AUC, the concentration of unchanged [14C]nimodipine in plasma represented only a small (maximally 37% in dogs after i.v. dose) to negligible (about 1%, monkey after oral dosing) part of the total radioactivity. Excretion of radioactivity via feces and urine was rapid in all species after both oral and intravenous dosing. Fecal (biliary) excretion was the major excretory route in rat and dog. The monkeys excreted about 40 to 50% via the urine. Residues in the body never exceeded 1.5% of the dose. [14C]nimodipine and/or its radiolabelled metabolites were secreted in milk of orally dosed lactating rats. Binding of [14C]nimodipine to plasma proteins of rat and dog was about 97%.

Animals↗
PubMed1985

Pharmacokinetics of Nimodipine. II. Communication: distribution, elimination and placental transfer in rats following single and multiple doses of [14C]nimodipine.

(+/-)Isopropyl-2-methoxyethyl-1,4-dihydro-2,6-dimethyl-4- (3-nitrophenyl)-3,5-pyridinedicarboxylate (nimodipine, Bay e 9736, Nimotop) is a calcium antagonist from the 1,4-dihydropBridine group which influences the cerebral blood flow. The active substance labelled with carbon-14 was administered orally or intravenously to rats at doses ranging from 1 to 10 mg/kg. The objective of the study was to determine the course of the distribution of total radioactivity among organs and tissues, to investigate the extent and kinetics of diaplacental transfer and to study the influence of continuous treatment over three weeks on concentrations and elimination kinetics in organs and tissues. The radioactivity concentration was determined qualitatively by whole-body autoradiography or quantitatively after autopsy. Following intravenous administration the radioactivity of [14C]nimodipine is distributed rapidly and uniformly. Later, and also after oral administration, the distribution pattern is strongly differentiated with high concentrations in the liver, kidneys and fat and low concentrations in the brain and testes and subsequently in the plasma. Within one day the concentration in the animal excluding the gastrointestinal tract falls by a factor of 25 and a slow elimination phase then ensues. Only a little of the radioactivity of nimodipine passes through the placental barrier. The distribution patterns and excretion routes detected in the foetus are essentially the same. The radioactivity concentration in the foetus was a factor of 8-15 lower than in the dam.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

[Non-invasive diagnosis of tachycardial heart arrhythmias].

The exact recognition of arrhythmias (AR) is the basis for decision making weather to treat AR or not. During the past the field of non-invasive, diagnostic tools approached from a simple 12-lead-routine ECG to higher sophisticated methods. This paper deals with the advantages and disadvantages of those non-invasive methods for AR-detection. Exercise Stress Tests (ET) are of value for the detection of "exercise induced" ventricular arrhythmias and tachycardias frequently related to ischaemia or cardiac congestion. ECG-Telemetry recognizes AR during the postinfarction-period during moderate exercise. The transmission of the ECG via the public telephone net (ECG-Telephone-Telemetry) is used in symptomatic patients possibly related to AR. With the ECG-TTM AR can be excluded in one third and in another third confirmed as cause for the symptoms. The Long-term ECG recording (Holter Monitoring) is today a frequently used method in the daily routine to detect AR and to control therapeutic effects. To avoid misinterpretations of the analysis-results we should be familiar with the system used and we have to look with criticism on the results presented by a machine. A new method, the registration of Late Potentials using the averaging technique of a high amplified ECG seems to be promising for risk-stratification: Patients with such Late-Potentials develop frequently ventricular tachycardia or die suddenly. Prior the use of invasive diagnostic methods or therapeutic interventions it is possible to recognize AR with the above mentioned complementary methods successfully.

Death, Sudden↗