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Biomedical subjects

M Wenzel

Publications and source records attributed to M Wenzel.

At least 127 records · Page 7Linked to original sources

[Organ distribution of ruthenocenyl biogenic amine derivatives--radiodiagnostic agents for the adrenals and ovaries?].

The organ distribution of 103Ru labelled ruthenocenyl derivatives of tyramine, histamine, benzylamine, phenylethylamine and homoveratrylamine were measured in rats. The derivatives of tyramine, histamine and benzylamine showed a high affinity for the adrenal and ovar. Adrenal/muscle ratios up to 2000:1 were gained but only if the dose was administered i.v. and was below 0.1 mumol/kg. The ruthenocenyl derivatives of tyramine labelled with 103Ru in the ruthenocene moiety or with 14C in the tyramine moiety showed a parallel distribution pattern but completely different from the distribution of 103RuCl3. This indicates that the tyramine derivatives are not destroyed in the body yielding Ru-ions. The advantages of the ruthenocenyl derivatives in comparison with the known amphetamine derivatives labelled with radioactive iodine are discussed.

Adrenal Glands↗

Ru-labeled ruthenocenoyl-glycine: comparison of clearance with hippuran.

Ruthenocenoyl-glycine (ruppuran) is a metallocene analog of iodo-labeled hippuran. After injection of 103Ru-labeled ruppuran and ruthenocenoyl-1,1'-diglycine in rabbits, measurement with external detectors revealed a very rapid accumulation in the kidneys followed by rapid excretion of the 103Ru activity. By measurement of the radioactivity concentration in plasma and urine samples collected 1-60 min after IV injection, the plasma clearance was calculated and compared with the clearance of 125I-labeled hippuran injected simultaneously. The clearance of ruppuran and ruthenocenoyl-diglycine in rabbits was found to be somewhat higher than that of hippuran. Extrapolating to man (1.73 m3), plasma clearance with both ruthenocene derivatives was approximately 500-600 ml/min. Biochemical data as well as the nuclear properties of 97Ru indicate the usefulness of 97Ru-labeled ruthenocenoyl-glycine as a radiopharmaceutical for kidney function studies.

Animals↗

Autoradiographical investigations on the affinity of acetyl-(103Ru)-ruthenocene for the adrenal glands of mice.

Whole-body autoradiography was used to investigate the distribution of acetyl-103-ruthenium-(103Ru)-ruthenocene in female mice 2 and 24 h after intravenous application. Two hours after the application of acetyl-(103Ru)-ruthenocene, the nasal mucosa, colon, lung, liver, spleen and especially the adrenal glands were labelled. After 24 h, apart from the absence of labelling of the colon, the labelling pattern did not differ from that obtained 2 h after application. Again, the adrenal glands were particularly strongly labelled. Microautoradiography was performed to investigate the distribution of acetyl-(103Ru)-ruthenocene within the adrenal glands. It was shown that acetyl-(103Ru)-ruthenocene labelling was restricted to the zona reticularis and the inner zona fasciculata of the adrenal cortex. After the stimulation of glucocorticoid synthesis in the adrenal cortex by adrenocorticotropic hormone (ACTH) pretreatment, the labelled area in the zona fasciculata was clearly enlarged. It is concluded that acetyl-(103Ru)-ruthenocene has an affinity for those regions of the adrenal glands where androgen and glucocorticoid synthesis occur.

Adrenal Glands↗

Sex-dependent organ distribution of radiopharmaceuticals: effect of hormones on localization of acetyl-103Ru-ruthenocene.

This paper demonstrates modification of organ distribution of a radiopharmaceutical, acetyl-103Ru-ruthenocene, by competing drugs. This radiopharmaceutical concentrates in kidneys of male Wistar rats 15-fold higher than in females of the same strain and age. This concentration in the male is age-dependent. Moreover, the retention of that radiopharmaceutical in male rats' kidneys is markedly reduced by pre-treatment of the rats with estradiol, and this effect is dose-dependent. Estradiol is competetively inhibiting the retention of acetyl-ruthenocene by the kidneys, the same effect also being obtained by tamoxifen, an anti-estrogen used clinically for regression of mammary carcinoma. Blocking the retention of acetyl-ruthenocene was also obtained by testosterone and cyproterone-acetate, as well as by ovariectomy, but the block after castration was partially compensated with time. Blood clearance of acetyl-ruthenocene is biphasic, with a first t 1/2 of about 12 h, and a second t 1/2 of about 48 h. The retention of the label is sex-specific also in mice, but only the female mice show a high adrenal affinity and significant changes in its organ distribution. These effects may be due to competition of acetyl-ruthenocene for steroid receptors, or due to its activation of enzymes that are responsible for its transformation into a bindable moiety.

Animals↗

Peri-operative infection prophylaxis with ornidazole and gentamicin in elective colonic surgery.

In a study of 60 patients undergoing elective colonic surgery peri-operative infection prophylaxis by the "one-shot' method was compared with that of 48-hour duration. The antibacterial agents used were ornidazole and gentamicin. Considering the patient population as a whole, no significant differences were found in the results. All the infectious complications which occurred post-operatively were due to bacterial contamination by aerobic pathogens. No anaerobic pathogens were detected in any of the cases.

Aged↗

[Systemic mezlocillin prophylaxis in elective colon surgery].

A prospective randomized, controlled study comprising 100 patients was performed to evaluate the effect of mezlocillin given prophylactically in elective colon surgery. Fifty-two patients were treated and 48 served as controls. Both groups were well-matched for age, sex, disease and surgical procedure. 2 g of mezlocillin were given intravenously before surgery and then every eight hours until the fifth postoperative day. The concentrations of mezlocillin in serum and tissues were determined in 20 patients and related to the MICs of the contaminants and the bacteria isolated postoperatively. A significantly lower incidence of intra-abdominal complications, peritonitis, urinary tract infections and wound infections was found in the mezlocillin group (10%) than in the controls (46%). The average number of postoperative hospital days decreased significantly from 23 days in the control group to 19 days in the mezlocillin group. The analysis of the bacteriological results gave no indication of a selection of resistant strains due to the prophylactic use of mezlocillin. No side-effects were found in connection with mezlocillin prophylaxis.

Adult↗

[Electron microscopic and morphometric studies on the in vitro differentiation of mitochondria in neurons of hippocampus explant cultures as affected by orotic acid and sodium orotate].

The influence of orotic acid and sodium orotate on the differentiation of mitochondria of the neurons within explantate cultures of the hippocampus of 18 day old rat embryos was investigated by means of morphometrical and stereological methods. The ultrastructure of the mitochondria in controls and pharmacologically influenced cultures was analysed on electronmicrographs after 3, 13 and 20 days in vitro. According to their morphological appearance and state of preservation the mitochondria were classified in 3 types: juvenile mitochondria (stage I), active mitochondria (stage II) and destroyed mitochondria (stage III). After 3 days of cultivation the neurons in cultures treated with orotic acid and sodium orotate showed significantly higher rates in the numerical density of mitochondria (ratio of the number of all mitochondria per unit volume of cytoplasm) in comparison with controls. Moreover, sodium orotate treatment lead to a significant increase especially in the numerical density of the mitochondria of stage II (active mitochondria) on the third day in vitro. However, the mitochondrial volume per unit volume of cytoplasma of the neurons in drug influenced cultures is lower than in controls for each of these dates--3., 13., and 20. day in vitro. The volume of the mitochondria increased under treatment with sodium orotate from the 3. up to the 20. day of cultivation but never reached the values of the uninfluenced controls. The plastic changes of the mitochondria due to pharmacological treatment with RNA--precursors demonstrate the possibility of a stimulating effect of the drug on the differentiation of neuronal mitochondria in vitro.

Animals↗

[The postoperative protein and energy metabolism during infusion therapy with high-calorie carbohydrate solutions, compared with low-calorie amino acid solutions].

In a comparative study two infusion regimens applicable via the peripheral veins were examined with regard to their efficacy for the protein and energy metabolism. 20 male metabolically normal patients having undergone gastric resections were divided into 2 groups: Group I received a combined 17.2% carbohydrate solution containing no amino acids, group II received a combined 5% carbohydrate solution together with a 2.5% amino acid solution. In group I an optimal protein sparing was observed with significantly lower serum urea levels than preoperatively and in group II. The serum urea levels of group II showed a significant increase without exceeding the upper normal range and thus indicated partial utilization of amino acids for gluconeogenesis. Nevertheless, the nitrogen balances of the postoperative days 1-4 in group II were significantly improved in comparison with group I. The amino acid utilization in group II was therefore considerable despite increased gluconeogenesis. The concentration of free fatty acids in the serum of group II which was significantly increased during the postoperative days 1-5 suggested an enhanced endogenous production of energy by way of lipolysis. In group II the low-dosed supply of carbohydrates produced a correspondingly lower insulin secretion which on the one hand enabled increased lipolysis and on the other hand resulted in the utilization of carbohydrates in insulin-independent organs essential for glucose utilization. In contrast to group II there was found to be a significantly lower concentration of free fatty acids in the serum of group I because of insulin-induced reesterification rates and impaired lipolysis.

Adult↗

[Influence of steroid hormones on drug disposition? Experiments with acetylruthenocene in mice and rats].

After injection of acetyl-[103Ru]-ruthenocene, high 103Ru concentration are found in adrenals of female mice. This was also found with acetyl-[3H]ruthenocene. On autoradiography only the adrenal cortex, not the medulla, was labelled. High 103Ru accumulations did not occur in the adrenals of male mice or rats, but male rats exhibited a very high 103Ru concentration in the kidney, with concentration kidney/muscle ratios up to 780:1. The 103Ru-concentration in the kidney of female rats was only 1/20 that of male rats. After application of testosterone propionate to female mice or estradiol to male rats a drastic change in organ distribution was observed: the 103Ru radioactivity in adrenals and kidneys decreased by a factor of 15. Similar to these results obtained with acetylruthenocen, a sex-specific distribution, but to a lesser extent, was found with dihydroacetylruthenocens.

Adrenal Glands↗