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Biomedical subjects

R Bosch

Publications and source records attributed to R Bosch.

At least 73 records · Page 4Linked to original sources
PubMed1985

The distribution of (5E)-(10S)-10,19-dihydroercalciol and its metabolites in serum of rats.

The distribution of radioactivity in serum of male rats (275 g) after oral administration of tritium labelled (5E)-(10S)-10,19-dihydroercalciol (dihydrotachysterol2) has been studied as a function of time and dose level. Nine distinct radioactive substances, chromatographing in the range between calciol and calcitriol, could be demonstrated. No attempt was made to establish chemical structures. After a single dose of 1.84 nmol, (5E)-(10S)-10,19-dihydroercalciol is very rapidly metabolized to more polar forms. The time course of appearance, ranging between 30 min and 1 day after administration, and the polarity of these substances indicated that they might be formed in sequence. The highest serum concentrations of the major substances occurred between 2 h and 10 h after administration, but compared with the dosage they were very low. In response to daily administration the concentrations of the major substances achieved steady-state levels within 1-4 days. The metabolism of (5E)-(10S)-10,19-dihydroercalciol was apparently not affected by its nutritional status at the dose level studied. After single administration of progressively increasing doses, ranging from 1.84 nmol to 1.84 mumol, the relative increments of the concentrations of the major substances rose in proportion to the relative increases of the dosage. The mechanisms responsible for the appearance of these substances in serum were found to be closely related. At dose levels up to 18.4 nmol feedback control was apparently absent.

Administration, Oral↗
PubMed1985

Isolation and identification of 25-hydroxydihydrotachysterol2 1 alpha,25-dihydroxydihydrotachysterol2 and 1 beta,25-dihydroxydihydrotachysterol2.

Three metabolites of orally administered dihydrotachysterol2 have been isolated in impure form from serum of rats. These metabolites have been identified as 25-hydroxydihydrotachysterol2 and two epimers of formula 1-ambo,25-dihydroxydihydrotachysterol2 by means of gas chromatography-mass spectrometry and ultraviolet absorption spectrometry. For the first time this provides evidence for 9,10-seco steroid hydroxylation at pseudo C3. The stereochemistry of the 1-hydroxyl group of the two epimers could be established tentatively by quantitative comparison of the mass spectra of their respective trimethylsilyl derivatives. Since purity requirements were not achieved, biological activities could not be determined.

Animals↗
PubMed1985

Treatment of renal osteodystrophy in children with dihydrotachysterol and 24,25-dihydroxyvitamin D3.

The effect of administration of 25 micrograms 24,25-dihydroxyvitamin D3 (24,25(OH)2D) combined with dihydrotachysterol (DHT2) on clinical, radiological, biochemical and bone histological parameters was assessed in ten children on chronic hemodialysis. Eight children had been treated with DHT2 prior to administration of 24,25(OH)2D. Addition of 24,25(OH)2D to the treatment resulted in a decrease in serum calcium values. Therefore higher doses of DHT2 were required to maintain serum-calcium levels between 2.4-2.8 mmol/l. Administration of 24,25(OH)2D did not modify the quality of bone, but histomorphometric investigation did show a significant reduction of the surface percentage of bone trabecula, in the iliac crest, covered with osteoclasts (oc%). Following the administration of 24,25(OH)2D an increase in bone mineralization was shown by X-rays of the wrists and measured by dual photonabsorptiometry. Addition of 24,25(OH)2D to the DHT2 treatment resulted in an increase in serum concentration of 24,25(OH)2D and a decrease in DHT2 levels. The present study suggests that administered 24,25(OH)2D interferes with DHT2 metabolism and increases DHT2 tolerance. Increased bone mineralization may be related to 24,25(OH)2D, a higher dose of DHT2 or both.

24,25-Dihydroxyvitamin D 3↗
PubMed1983

Synthesis of [10S(19)-3H]-dihydrotachysterol2 from ergocalciferol and preliminary investigations into its metabolic fate in rats.

Dihydrotachysterol2 (DHT2), a 5,6-trans derivative of vitamin D2, is very successfully used in the treatment of hypoparathyroidism and renal osteodystrophy. However, the metabolism and the action of DHT2 are poorly understood. Investigations into metabolism of DHT2 start at the synthesis of the radioactively labelled compound. This paper deals with a two-step synthesis of [10S(19)-3H]-dihydrotachysterol2 from vitamin D2. Vitamin D2 can be converted into 5,6-trans vitamin D2 by iodination under irradiation and by triplet-sensitized isomerization. The first method led to unwanted side-reaction products which were difficult to separate from 5,6-trans vitamin D2. Triplet-sensitized isomerization yielded merely 5,6-trans vitamin D2 which could be separated from the residual starting material by chromatography on silica gel and recrystallization. [10S](19)-3H]-Dihydrotachysterol2 with a specific radioactivity of 56 kCi/mol was prepared from 5,6-trans vitamin D2 via partial, homogeneous catalytic reduction of the 10S(19) double bond with tritium gas. It was purified by high-performance liquid chromatography (h.p.l.c.) and characterized by chromatography and ultra-violet absorption spectrophotometry. The biological usefulness of the material was demonstrated in rats following intragastric administration. Blood was collected after 24 and 48 h and fractionation of serum lipids on h.p.l.c. showed 5 peaks of radioactivity.

Animals↗
PubMed1983

Changes in bone metabolism during treatment of acromegaly.

Bone metabolism was studied in 17 acromegalic patients, who responded to either medical treatment with bromocriptine (12 patients), or to transsphenoidal surgery (5 patients). Parameters of bone turnover decreased, e.g. serum acid phosphatase (9.2 +/- 0.7 vs 8.1 +/- 0.6 U/l, P less than 0.05) and the ratio of hydroxyproline/creatinine (33.6 +/- 4.4 vs 18.3 +/- 2.0, P less than 0.01) in the urine. No changes were observed in parathyroid function or concentrations of calcitonin. Serum 1,25-dihydroxycholecalciferol decreased (32.6 +/- 3.6 vs 20.6 +/- 1.8 ng/l, P less than 0.01) and 24,25-dihydroxycholecalciferol increased (4.3 +/- 0.6 vs 6.7 +/- 1.0 micrograms/l, P less than 0.05). No correlation between the percentual changes in serum growth hormone levels and 1,25-dihydroxycholecalciferol was found, suggesting an indirect effect of growth hormone on the renal 25-hydroxycholecalciferol-1-alpha-hydroxylase. The possible mechanisms involved are discussed, including the effects of growth hormone and somatomedin on bone.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1982

Serum concentrations of dihydrotachysterol-2 in the treatment of osteoporosis and hypoparathyroidism.

A method for the quantitative estimation of dihydrotachysterol-2 is described using high performance liquid chromatography coupled to an UV monitor. Since radioactive labelled DHT2 is not available, recovery is based on the assumption that dihydrotachysterol-2 and cholecalciferol behave identically during chromatic procedures. Evidence is presented to support this assumption. In patients treated with DHT2 the serum concentrations of DHT2 rose in proportion to the administered dose.

Chromatography, High Pressure Liquid↗
PubMed1982

Interlaboratory variation of vitamin D1) metabolite measurements.

Interlaboratory variation of the measurement of 25-hydroxy vitamin D, 24,25-dihydroxy vitamin D and 1,25-dihydroxy vitamin D by six laboratories in the Netherlands was studied. Three different serum samples and two different standard solutions of each metabolite were assayed. Substantial interlaboratory variation was found for the measurement of serum samples. The mean interlaboratory CV's for the 25-hydroxy vitamin D, 24,25-dihydroxy vitamin D and 1,25-dihydroxy vitamin D assays in the three sera were 48%, 38% and 20% respectively. The measurement of standard solutions of all metabolites showed relative little variation (mean CV 8%). The small number of samples allowed no evaluation of intralaboratory variation. The much higher CV's of the measurement of serum samples, when compared to standard solutions, may be attributed to differences in extraction and purification procedures which are probably responsible for the presence of varying amounts of interfering substances during the final quantification of metabolites.

24,25-Dihydroxyvitamin D 3↗
PubMed1982

Lack of influence of the anabolic steroid nandrolondecanoate on bone metabolism.

Eleven male patients with rheumatoid arthritis were treated with the anabolic steroid nandrolondecanoate and parameters of calcium and bone metabolism were studied. No changes were found in the concentrations of calcium, phosphorus or hydroxyproline in serum and urine (corrected for the creaturia). A significant decrease (P less than 0.01) was observed in the levels of alkaline phosphatase, but this was attributed to a change in liver enzymes, because the gamma glutamyl transpeptidase fell. Acid phosphatase levels showed an increase, possibly as a result of an effect of nandrolondecanoate on the prostate. No change was found during treatment in the serum levels of parathyroid hormone, calcitonin, 25 hydroxyvitamin D, 24, 25 dihydroxyvitamin D and 1.25 dihydroxyvitamin D. A seasonal fluctuation was observed for 25 hydroxyvitamin D and 24, 25 dihydroxyvitamin D, but not for 1,25 dihydroxyvitamin D. It was concluded that short-term treatment with the anabolic steroid nandrolondecanoate did not result in changes in parameters of calcium and bone metabolism.

Adult↗
PubMed1976

Public health advantages of biological insect controls.

Biological control is not new, it is simply newly appreciated. This renewed appreciation stems from the widespread insecticide treadmill which is largely a product of insecticide disruption of the balance of insect communities. Biological control is a natural phenomenon; the regulation of plant and animal numbers by natural enemies. In this broad sense, biological control is vital to public health because it keeps the myriad insect species from out-competing us. It also has direct public health advantages as where natural enemies are manipulated to control disease vectoring insects. Insecticide distruption of biological control by insecticides and the resulting pesticide treadmill have serious public health implications. One is the increased pesticide load in the environment. The other is the acceleration of pesticide resistance in disease vectoring insects. The treadmill and its associated hazards will not abate so long as chemical control dominates our pest management strategy.

Environmental Health↗