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Biomedical subjects

R Ziegler

Publications and source records attributed to R Ziegler.

At least 379 records · Page 21Linked to original sources

1,25-Dihydroxyvitamin D3 prevents the decrease of bone mineral appositional rate in rats with inflammation-mediated osteopenia (IMO).

We have studied the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on bone mass and bone mineral appositional rate in intact rats and rats with inflammation-mediated osteopenia (IMO), where osteoblast number and mineral appositional rate are decreased. 1,25(OH)2D3 prevents IMO-specific bone loss when given in a daily dose of 25 ng per rat, but does not when given in higher doses. The hormone was effective, when given over the complete duration of the experiment (21 days), but not when given over shorter time periods (7 and 14 days, respectively). 1,25(OH)2D3 prevents IMO-dependent reduction in mineral appositional rate and leads to an only moderate increase in intact rats. We conclude, that 1,25(OH)2D3 is more effective in stimulating mineral appositional rate in rats with IMO where mineral apposition is impaired.

Animals↗

Antiestrogen and antiandrogen administration reduce bone mass in the rat.

In mature female and male rats sex hormone deficiency was produced by surgical castration and by antiestrogen or antiandrogen administration. For the latter purpose we used the nonsteroidal antiestrogens tamoxifen, keoxifene (LY156758) and tetramethylhexestrol, and the steroidal antiandrogen cyproterone acetate. Dosages of 0.4 mg tamoxifen/rat/day and isomolar dosages of keoxifene and tetramethylhexestrol led to a bone mass reduction which was comparable to ovariectomized rats. Cyproterone acetate showed, at 10 mg/rat/day, a similar decrease in bone mass like orchidectomy. The often discussed intrinsic estrogen activity of the antiestrogens was present only in the highest dosage tested of tamoxifen. Keoxifene and tetramethylhexestrol showed no estrogenic effects, but this may be a dosage problem. Cyproterone acetate revealed no androgenic side-effects. These results indicate that antigonadal hormone drugs reduce bone mass to a varying extent.

Androgen Antagonists↗

Reversible desensitization of calcitonin secretion by repetitive stimulation with calcium.

The extracellular ionized calcium concentration (Ca2+) is a main regulator of calcitonin (CT) release. Calcium-induced CT secretion differs for acute versus long-term alterations of Ca2+. Using the rat C cell line rMTC 6-23 we have investigated the effect of repetitive stimulation by Ca2+ on CT release. After a Ca-induced initial rise of CT secretion, repetitive Ca stimulation led to a decline of CT release to unstimulated levels (after about 4 h). Reversing the high Ca2+ concentration (2.0 mM) to basal (1.1 mM) for 2 h and then increasing Ca2+ again resulted in a restored stimulatory action of Ca2+ (about 100% increase above the control). In contrast, repetitive stimulation with the dihydropyridine Ca channel agonist Bay K-8644 showed an unchanged stimulatory effect, as observed for the cAMP analog 8-bromo-cAMP, too. The results indicate that the reversible desensitization of Ca-induced CT secretion might be due to a modification of the voltage-dependent Ca channels proximal to or at the site of Bay K-8644 action.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Rhythmic oscillations of cytosolic free calcium in rat C-cells.

The relationship between stimulation of single C-cells (rMTC-6-23 cell line) with extracellular calcium, glucagon or 8-bromo-cAMP and fluctuations of intracellular free calcium concentration was studied. After pretreatment of rMTC cells with either 1 microM glucagon (30-60 min) or 1 mM 8-bromo-cAMP (5 min) [Ca2+]i started to oscillate when extracellular calcium was raised to 3 mM. These fluctuations in [Ca2+]i could be stopped by chelating the external calcium with EGTA or by adding calcium channel blockers. The voltage-dependent calcium channels in the plasma membrane seem to play a major role in maintaining the oscillations of [Ca2+]i.

8-Bromo Cyclic Adenosine Monophosphate↗

Early reversible induction of leukotriene synthesis in chicken myelomonocytic cells transformed by a temperature-sensitive mutant of avian leukemia virus E26.

We used chicken myelomonocytic cells transformed by a temperature-sensitive mutant of the myb/ets oncogene-containing avian leukemia virus E26 to study the regulation of leukotriene (LT) synthesis during macrophage differentiation. Cells exposed to arachidonic acid and the Ca2+ ionophore 23187 produced up to 180 times more LTs at the nonpermissive temperature (42 degrees C) than at the permissive temperature (37 degrees C). Induction of LT synthesis was detectable within 2 hr after temperature shift, whereas conventional macrophage markers became evident after 2-3 days. N-Formylmethionylleucylphenylalanine, opsonized zymosan, and complement factor C5a induced LT synthesis in temperature-sensitive mutant-transformed cells only when the cells were maintained at 42 degrees C, and this effect was blocked by pertussis toxin. When cells were kept at 42 degrees C for 48 hr and then shifted back to 37 degrees C to induce retrodifferentiation, LT synthesis rates declined within 8 hr and reached near control values within 36 hr. Retrodifferentiation also led to decreased LT synthesis in response to N-formylmethionylleucylphenylalanine, opsonized zymosan, and C5a. These results indicate that activation of the 5-lipoxygenase pathway is a very early event in the macrophage differentiation pathway that is directly or indirectly controlled by the temperature-sensitive v-myb protein.

Animals↗

Reversible bone loss in women treated with GnRH-agonists for endometriosis and uterine leiomyoma.

Oestrogen deficiency at the menopause is associated with changes in calcium and bone metabolism. Hypo-oestrogenism induced by the use of GnRH-agonists is clinically useful in the treatment of oestrogen-dependent diseases. This study was done to investigate calcium homeostasis and bone metabolism of pre-menopausal women in a GnRH-agonist-induced pseudo-menopause. Eighteen patients with endometriosis or uterine leiomyoma received monthly i.m. injections of 3.2 mg of long-acting D-Trp-6-LHRH over a 6-month period. Plasma oestradiol-17 beta and progesterone levels under treatment were significantly decreased to the levels of the early follicular phase. Plasma total calcium, serum osteocalcin and plasma alkaline phosphatase concentrations increased, while plasma phosphate levels did not change. Levels of 1,25-dihydroxyvitamin D3 decreased significantly, but 25-hydroxyvitamin D3 values remained constant. Trabecular bone mineral density of lumbar spine decreased continuously during the 6-month period. Nine women completed 6-9 months follow-up. In these women bone loss was reversible. Cortical bone measurements at the proximal radius showed no change during oestrogen deficiency. In conclusion, our findings demonstrate that GnRH-agonist-induced bone loss is reversible. Furthermore, they suggest that the state of pseudo-menopause induced by GnRH-agonist may serve as a model for further pathophysiological studies on calcium homeostasis and bone metabolism in the post-menopause.

Adult↗

Life-table analysis of progression to diabetes of anti-insulin autoantibody-positive relatives of individuals with type I diabetes.

Cytoplasmic islet cell antibody-negative (ICA-; less than 20 Juvenile Diabetes Foundation units, n = 1670) and ICA+ (n = 42) first-degree relatives of type I (insulin-dependent) diabetic individuals were studied for competitive insulin autoantibodies (CIAAs) with a radioassay. Overall, 3.7% of first-degree relatives (64 of 1712) were CIAA+. Of ICA- relatives, 2.7% (45 of 1670) exceeded the upper limit of our normal CIAA range (greater than 39 nU/ml), and 45% (19 of 42) of ICA+ relatives exceeded this normal range. Follow-up serums for repeat CIAA determination have been obtained from 16 of the nondiabetic CIAA+/ICA- individuals (time between samples, 0.4-5.8 yr). Fourteen of these 16 (87%) CIAA+/ICA- relatives were found to still be positive on follow-up, and 2 of the relatives who were positive on the first determination were negative on their follow-up test. With a mean follow-up of approximately 2 yr, 4 of 45 (9%) of the CIAA+/ICA- relatives, 5 of 23 (22%) of the ICA+/CIAA- relatives, and 12 of 19 (63%) of the CIAA+/ICA+ relatives developed diabetes. Life-table analysis indicated that, overall, 53% of CIAA+ relatives become diabetic after 5 yr of follow-up versus 65% of ICA+ relatives. Also by life-table analysis, the predicted risk after 5 yr of follow-up for progression to diabetes is 17% for CIAA+/ICA- relatives, 42% for ICA+/CIAA- relatives, and 77% for CIAA+/ICA+ relatives. The highest rate of progression to diabetes was found in ICA+ relatives with CIAA levels greater than 150 nU/ml (100% projected to be diabetic within 5 yr, P less than .008 vs. ICA+/CIAA- relatives).

Autoantibodies↗

Calcitonin secretion and cyclic AMP-efflux from C-cells, stimulated by glucagon and either calcium or Bay K 8644.

The interaction of glucagon and either calcium or Bay K 8644 on calcitonin (CT)-release and cAMP-efflux was studied in a rat C-cell line, (rMTC 6-23). CT secretion was stimulated by glucagon up to 216%, ionized calcium (Ca++) up to 112%, and Bay K 8644 up to 81% above the control. The combination of glucagon with either Ca++ or Bay K 8644 resulted in an additive effect. cAMP-efflux was grossly incremented by glucagon (536 pmol/mg), slightly by Ca++ (11.6 pmol/mg) and not at all by Bay K 8644 (less than 3 pmol/mg). The combination of glucagon with either calcium or Bay K 8644 caused a reduction of the cAMP-increase obtained by glucagon alone. These data suggest complex interactions between the cAMP and the intracellular calcium-dependent pathway, but an additive effect of the two pathways on CT-release.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

[Contamination of drinking water with atrazine, simazine and nitrate in the Rastatt, Baden-Baden and Bühl areas].

Drinking water samples taken from public waterworks and private water sources were examined between November 1986 and July 1988 for atrazin and simazin content in the area of the Rastatt Public Health Office and its subsidiary offices in Baden-Baden and Bühl (located in the Federal German Land of Baden-Württemberg). The overall result of the examination of 41 samples taken from public waterworks and of 29 samples taken from private water sources showed that the drinking water offered by the public waterworks from reservoirs in areas declared as protected drinking water areas, is generally free from pesticide residues. However, water from private sources must be considered as extremely exposed to risk. Of 29 wells that were tested, only three were free from atrazin and only 5 free from simazin. The nitrate situation can presently be considered as being under control. Limit values have not been exceeded anywhere except for one private well.

Atrazine↗

[Follow-up in determining of blood lead levels in children, adolescents and adults in the Rastatt heavy metal pollution area].

A study was conducted in 1981 and again in 1984 to determine the amount of lead and cadmium contamination of the population in the industrial area of Rastatt in the Land of Baden-Württemberg, W. Germany. 522 persons were analysed, including 91 children and adolescents between 1 and 18 year of age. A general threat to the population by lead and cadmium could be excluded. The factory suspected of being responsible for the environmental contamination has since stopped production. In 5 children from the centre of the studied area we found enhanced blood lead levels but there were no signs of any clinically relevant disease. Four of these children were followed up regularly from 1984 onwards. A control checkup at the end of 1988 showed that there was a trend towards reduction of the blood lead levels. These levels did not show anything abnormal in the remaining 22 persons subjected to the checkup.

Adolescent↗

Modulation of calcitonin secretion by modification of calcium channels?

Voltage-dependent calcium channels (VDCC) regulating Ca++ influx through the cellular plasma membrane play a major role in the Ca(++)-induced calcitonin (CT) secretion. Using rat C-cells (rMTC 6-23 cell line), we have studied the effect of repetitive stimulation by either Ca++ (2 mM) or glucagon (10 microM) or epinephrine (10 microM) on CT secretion. Following a Ca(++)-induced initial rise, CT release declined to basal levels after about four hours despite high Ca++; addition of 10 microM glucagon to the "Ca++ desensitized C-cells" yielded the normal stimulatory effect of glucagon on CT release. Repetitive stimulation with glucagon showed a constant stimulatory action over an eight-hour period. In contrast, repetitive stimulation with 10 microM epinephrine caused an initial rise followed by a gradual decline of CT release over six hours. The observed desensitization of Ca(++)-induced CT secretion may be due to a modification of VDCC in C-cells. Whether or not the desensitization of epinephrine-induced CT release occurs independently of the regulation of VDCC remains unclear.

Animals↗

[Internal medicine aspects of endocrine tumors. The hypophysis, epithelial bodies and adrenal glands].

Endocrine tumors are characterized by an overproduction of hormones leading to a typical clinical picture and/or by hormone deficiency induced by damage to the glands. Hormone deficiency or overproduction must be determined precisely, as must the morphology and localization of the tumor, before therapy starts. Hormone deficiency needs to be substituted. Specific therapies for hormone suppression and/or inactivation of the endocrine cells have been developed for some tumors, e.g., bromocriptine for prolactinoma, and o,p'-DDD for adrenocortical tumors.

Adrenal Gland Neoplasms↗

[Echographic localization diagnosis of enlarged parathyroid glands].

The authors report on their own experience with the localization of enlarged parathyroid glands by sonography. In a study of 248 patients with hyperparathyroidism, they obtained a sensitivity of 57% and a specificity of 81%, with an overall accuracy of 74%. These results are discussed in detail.

Humans↗