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M M Weber

Publications and source records attributed to M M Weber.

At least 73 records · Page 4Linked to original sources
PubMed1991

Effect of ketoconazole on human ovarian C17,20-desmolase and aromatase.

Ketoconazole, an imidazole antimycotic drug, inhibits steroid biosynthesis in adrenal and testicular tissue by blocking cytochrome P-450 dependent enzymes. To study the effect of ketoconazole on steroid biosynthesis in the human ovary we incubated human ovarian tissue (mainly theca cells) or granulosa cells with radiolabeled precursors and increasing concentrations of ketoconazole. After incubation, steroids were extracted and separated by thin layer chromatography (TLC). Activity of C17,20-desmolase and aromatase was estimated by measuring the amount of their radioactive products with liquid scintillation counting. After incubation of ovarian tissue with [3H]17-hydroxyprogesterone the production of [3H]androstenedione was reduced by increasing concentrations of ketoconazole (0-200 microM) to a minimum of 31% of basal production. This indicates a strong inhibition of ovarian C17,20-desmolase by ketoconazole with a 50% inhibiting concentration (IC50) of 23 microM. After incubation of human granulosa cells with ketoconazole (0-2000 microM) and [3H]androstenedione the production of [3H]estrone and [3H]estradiol was suppressed to minimally 37 and 35% of basal values, indicating a significant inhibition of ovarian aromatase. IC50-values were 105 microM ketoconazole for estradiol and 130 microM for estrone. In conclusion, ketoconazole was shown to inhibit human ovarian C17,20-desmolase and aromatase in vitro. As in human adrenals and testes ovarian C17,20-desmolase seems to be most sensitive to the inhibitory effect of ketoconazole.

17-alpha-Hydroxyprogesterone↗
PubMed1991

The influence of ketoconazole on human adrenal steroidogenesis: incubation studies with tissue slices.

OBJECTIVE: The influence of ketoconazole on the various enzymes of human adrenal steroid biosynthesis was examined in vitro. MEASUREMENTS: After incubation of human adrenal tissue slices with labelled precursors and ketoconazole (0-2000 microM), radioactive metabolites were separated by thin-layer chromatography and quantified by liquid scintillation counting. Enzyme activity was assessed by measuring conversion of tritium-labelled precursors to products. RESULTS: In vitro, ketoconazole showed a significant inhibition on the following adrenal enzyme systems (with decreasing activity): C17,20-desmolase (IC50 2 microM), 16 alpha-hydroxylase (IC50 9 microM), 17 alpha-hydroxylase (IC50 18 microM), 18-hydroxylase (IC50 28 microM), and 11 beta-hydroxylase (IC50 35 microM). In the tested concentrations ketoconazole had no inhibitory effect on the 21-hydroxylase, the 3 beta-hydroxysteroid dehydrogenase and the 20-hydroxysteroid dehydrogenase component of the C17,20-desmolase enzyme system. CONCLUSIONS: The data are in accordance with clinical findings where a strong suppression of serum androgen levels by relatively selective inhibition of C17, 20-desmolase has been assumed. The predominant blocking effect of ketoconazole on adrenal as well as on gonadal androgen biosynthesis might be of clinical benefit in the management of hyperandrogenic states.

Adrenal Glands↗
PubMed1991

[Not Available].

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Academies and Institutes↗
PubMed1991

["A research institute for psychiatry...". The development of the German Research Institution for Psychiatry in Munich between 1917 and 1945].

The "Deutsche Forschungsanstalt für Psychiatrie" (DFA) in Munich, one of the most important research institutes in the field of theoretical and clinical psychiatry was founded in 1917 by Emil Kraepelin. Its financial existence between the World Wars was guaranteed by enormous donations from the jewish American James Loeb. The scientific work done by Walther Spielmeyer (neuropathology), Felix Plaut (serology), Kurt Schneider (clinical psychiatry) and Ernst Rüdin (psychiatric genetics) earned the DFA the reputation as an international center for psychiatry and neurology. During the "Third Reich", Ernst Rüdin cooperated with the national socialist health system. His genetic concepts supported eugenic laws such as compulsory sterilization of psychotic patients. These complex interrelations underscore the DFA's importance for the recent history of medical science in Germany.

Academies and Institutes↗
PubMed1990

Anticonvulsants as adjuncts for the neuroleptic treatment of schizophrenic psychoses: a clinical study with beclamide.

A recent study showed an adjuvant effect of carbamazepine in the neuroleptic treatment of acute schizophrenic psychoses. Since beclamide (beta-chlorpropionamide) was reported to reduce the neuroleptic doses required, the combination haloperidol-beclamide was tested using a double-blind, placebo-controlled study in 23 inpatients with an acute schizophrenic psychosis. In both groups patients received haloperidol and either beclamide or placebo. Every 7 d the treating psychiatrist could increase the haloperidol dose by 3 mg per day if clinically necessary. Chlorprothixene and biperiden were on hand as additional medication. After 28 d beclamide or placebo were discontinued under a constant dose of haloperidol and a final rating with the Inpatient Multidimensional Rating Scale, Brief Psychiatric Rating Scale, and Extrapyramidal Symptom Scale was carried out. Without reaching statistical significance, the beclamide group needed a lower dose of neuroleptic medication, showed fewer side effects and a more pronounced psychopathological improvement.

Anticonvulsants↗
PubMed1990

[Psychological effects of previous treatment experiences with neuroleptics].

Stable attitudes towards illness and treatment and a high compliance with a 5-week low dose neuroleptic treatment (with/without anticonvulsant adjuvant therapy) were observed in 18 inpatients with schizophrenic disorders (ICD-9, DSM-III-R). Patients having previously received neuroleptics showed more compliant attitudes and greater satisfaction with the treatment, and complained less often about side effects. Noncompliant attitudes were related to dissatisfaction with treatment and self-rated depressed mood. Results of this pilot study are discussed, considering methodological problems and possible therapeutic implications.

Adult↗
PubMed1989

Inhibition of human adrenal androgen secretion by ketoconazole.

The effect of ketoconazole on adrenal androgen secretion was examined in 15 patients with elevated serum androgens. In a dose of 600 mg per day orally ketoconazole inhibited the biosynthesis of all measured androgens. The mean reduction in serum levels of dehydroepiandrosterone sulfate was 32%, of dehydroepiandrosterone 54%, of androstenedione 52%, and of testosterone 43%; mean serum levels of cortisol only fell by 19%. The reduction in serum androgen levels was first significant 24 h after beginning of treatment and persisted as long as the drug was administered. We conclude that ketoconazole inhibits adrenal androgen biosynthesis more pronouncedly than cortisol biosynthesis more pronouncedly than cortisol biosynthesis. This might be of clinical benefit in the treatment of hirsutism and other states of androgen hypersecretion.

ACTH Syndrome, Ectopic↗
PubMed1989

Psychotoxic effects of ofloxacin.

Two cases of organic psychosis, induced by the new chemotherapeutic agent ofloxacin (Tarivid), are described. According to DSM-III-R and ICD 10 (draft, 1987) both cases present as different, yet well-defined diagnostic categories: the new diagnostic systems appear to be superior and markedly more differentiated than ICD-9, since they provide a more exact and comprehensive description and more specific diagnostic allocation, especially in substance-specific syndromes. The possible involvement of GABAergic and monaminergic mechanisms in this psychotic symptomatology and their relationship to hypersynchronous states are discussed in detail.

Adult↗
PubMed1988

Current and historical concepts of opiate treatment in psychiatric disorders.

In recent years psychiatric research has rediscovered the theoretical and clinical importance of opiates, especially for the understanding of depressive disorders. However, opiate treatment is not a new therapeutic concept in psychiatry. The use of opium for "melancholia" and "mania" may be traced to ancient classical medicine. After Paracelsus and Sydenham, the psychiatry of the German Romantic Era widely discussed therapeutic opium use with the Engelken family going on to develop a structured opium treatment of depression in the first half of the nineteenth century. Although the underlying scientific problems of psychiatric opium therapy were never solved, it gained an outstanding position as a practical treatment for over 100 years.

Depressive Disorder↗
PubMed1988

Influence of soy protein or casein on pre-established atherosclerosis in rabbits.

Atherosclerosis was established in rabbits by feeding 1% cholesterol and 4% corn oil for two months. The rabbits were placed into five groups of equal average cholesterol level (2876 mg/dl) one of which was autopsied. The four remaining groups were placed on commercial ration (CR), CR plus 4% corn oil, or semipurified diets containing 14% coconut oil and 25% soy protein or casein. After two months, serum cholesterol levels in CR, CR plus corn oil, soy and casein groups had fallen by 91, 80, 81, and 64%, respectively. Aortic sudanophilia (%) in these four groups had increased by 106, 213, 238, and 25%, respectively. The findings confirm earlier observations that rabbit atherosclerosis does not regress when the atherogenic stimulus is removed.

Animals↗
PubMed1987

Inhibition of chemically induced mammary and colon tumor promotion by caloric restriction in rats fed increased dietary fat.

Tumor promotion associated with increased dietary fat may be inhibited by reduction in total caloric intake. This hypothesis was tested in rats given either 7,12-dimethylbenz(a)anthracene to induce mammary tumors or 1,2-dimethylhydrazine to induce colon tumors. One week after dosage with either carcinogen, the rats were fed semipurified diets that provided 4% fat with ad libitum calories or 13.1% fat with a reduction of calories by 40% from ad libitum intake. Rats treated with 7,12-dimethylbenz(a)anthracene and subjected to caloric restriction weighed 40% less than those fed ad libitum; rats treated with 1,2-dimethylhydrazine were heavier at the onset of caloric restriction and lost weight and weighed approximately 40% less than animals fed ad libitum. At 20 weeks after 7,12-dimethylbenz(a)anthracene administration, rats fed ad libitum had 80% tumor incidence while in those fed restricted calories, 20% had tumors (P less than 0.001). All other measures of mammary tumor growth were significantly reduced in rats given restricted calories. Six months after 1,2-dimethylhydrazine administration, colon tumor incidence was 100% in rats fed ad libitum and 53% in those fed the calorie-restricted diet (P less than 0.001). This reduction of colonic carcinogenesis was seen despite a significant increase in mucosal labeling index following [3H]thymidine autoradiography. This paradoxical finding may be due to the increased fat content of the calorie-restricted diet. These data demonstrate that the tumor-promoting effects of dietary fat can be more than offset by a reduction in total caloric intake and that the promoting effect of fat may be due, at least in part, to its greater caloric density.

Animals↗
PubMed1986

Calories, fat and cancer.

The experiments reported are part of our effort to dissociate the tumor-enhancing effects of dietary fat and high caloric intake. Rats either were fed ad libitum diets containing 4% corn oil or their calories were restricted by 40% and their diets contained 13.1% corn oil. Incidence of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors was 80% in rats fed ad libitum and 20% in those fed the calorie-restricted diets. Incidence of 1,2-dimethylhydrazine (DMH)-induced colon tumors was 100% in rats fed ad libitum and 53% in those whose caloric intake was restricted by 40%. The tumor yield (tumors per tumor-bearing rat) was significantly lower in rats on caloric restriction. In another series, rats were fed diets containing 5, 15 or 20% corn oil ad libitum or were fed calorie-restricted (by 25%) diets which provided 20 or 26.6% corn oil (therefore, the same absolute amount of fat was consumed in each of the pair-fed groups). Tumor incidence and tumor yield in the two calorie-restricted groups were similar to those seen in the rats fed 5% fat ad libitum; tumor burden (total g of tumor) was 45-65% lower in the calorie-restricted rats. The data suggest that caloric intake is a more stringent determinant of tumor growth than fat intake.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Solubilization, purification, and characterization of succinate dehydrogenase from membranes of Mycobacterium phlei.

Succinate dehydrogenase (SDH) was solubilized from membranes of Mycobacterium phlei by Triton X-100 with a recovery of about 90%. The solubilized SDH was purified about 90-fold by Sephacryl S-300, DEAE-cellulose, hydroxylapatite, and isoelectric focusing in the presence of Triton X-100 with a 20% recovery. SDH was homogeneous, as determined by polyacrylamide gel electrophoresis in nondenaturing gels containing Triton X-100. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the enzyme revealed two subunits with molecular weights of 62,000 and 26,000. SDH is a flavoprotein containing 1 mol of flavin adenine dinucleotide, 7 to 8 mol of nonheme iron, and 7 to 8 mol of acid-labile sulfide per mol of protein. Using phenazine methosulfate and 2,6-dichloroindophenol as electron acceptors, the enzyme had an apparent Km of 0.12 mM succinate. SDH exhibited a sigmoidal relationship of rate to succinate concentration, indicating cooperativity. The enzyme was competitively inhibited by fumarate with a Ki of 0.15 mM. In the absence of Triton X-100, the enzyme aggregated, retained 50% of the activity, and could be resolubilized with Triton X-100 with full restoration of activity. Cardiolipin had no effect on the enzyme activity in the absence of Triton X-100, but it stimulated the activity by about 30% in the presence of 0.1% Triton X-100 in the assay mixture. Menaquinone-9(2H), isolated from M. phlei, had no effect on the enzyme activity either in the presence or absence of Triton X-100.

Cardiolipins↗