PubMed Health⌕ Search

Biomedical subjects

C Onkelinx

Publications and source records attributed to C Onkelinx.

16 recordsLinked to original sources
PubMed1991

Effects on bowel motility of misoprostol administered before and after meals.

Prostaglandin analogues, used in the treatment of duodenal and benign gastric ulcer and in the prevention of gastric ulceration caused by non-steroidal anti-inflammatory drugs, are frequently associated with gastrointestinal side effects, particularly diarrhoea and abdominal cramps. We investigated the effects of misoprostol, a prostaglandin E1 derivative, on bowel motility and faecal loss of fat, water and bile acids in relation to its postprandial vs. preprandial administration. Twelve healthy subjects participated in a double-blind crossover study comparing three 5-day courses of therapy with a washout period of 1-2 weeks between courses. Following a Latin Square design, the dosing regimens were (a) 400 micrograms misoprostol b.d. after meals and placebo b.d. before meals; (b) 400 micrograms misoprostol b.d. before meals and placebo b.d. after meals; (c) placebo before and after meals. Orocaecal transit time measured by H2 breath tests following lactulose administration, was shortest during pre-prandial dosing but was also significantly decreased during post-prandial dosing. The overall treatment difference was highly significant (P less than 0.001), and the difference between each pair of treatments was also statistically significant. Whole bowel transit time studied by means of 3H-PEG 4000 determination in stools, was shorter for the two misoprostol regimens but statistical significance was borderline. The number of stools passed per day was similar in the three groups. During both misoprostol dosing periods, stools were less formed and their content of water, fat and bile acids was higher. There was also more urgency, flatulence, abdominal pain and nausea. It is concluded that the gastrointestinal side effects caused by misoprostol are mainly based on an increased orocaecal transit time. The effects are more important when the drug is administered before meals than after meals.

Adolescent↗
PubMed1985

Effects of thionaphthene 2-carboxylic acid and related compounds on bone resorption in organ culture.

We have compared the effects of thiophene 2-carboxylic acid (TCA) and a number of sulfur- and nitrogen-containing analogs for their ability to inhibit bone resorption in organ cultures of fetal rat long bones. Four compounds,--thionaphthene-2-carboxylic acid (TNCA), dibenzo-thiophene-4-carboxylic acid, indole-2-carboxylic acid and carbazole-1-carboxylic acid--caused a dose-related inhibition of PTH-stimulated bone resorption, although TCA was ineffective in this system. TNCA at 3 X 10(-4) M or 10(-4) M was the most potent inhibitor of PTH-stimulated bone resorption and was selected for further study. TNCA also inhibited stimulation of resorption by prostaglandin E2 and 1,25-dihydroxyvitamin D. Unlike calcitonin, the effect of TNCA was persistent and did not show escape. Moreover, TNCA could inhibit resorption in bones that had previously escaped from calcitonin. TNCA did not appear to be a nonspecific toxin, since it did not decrease incorporation of [3H]thymidine or [3H]proline into fetal rat long bones. The fact that resorption in unstimulated cultures was only decreased when the control rates were high also argues against nonspecific toxicity. Moreover, this suggests that TNCA will be most effective under conditions of accelerated bone resorption when an inhibiting effect is most desirable.

Animals↗
PubMed1985

Thionapthene-2-carboxylic acid: a new antihypercalcemic agent.

Thiophene-2-carboxylic acid (TCA) was previously shown to be hypocalcemic in the rat. We have compared TCA with thionapthene-2-carboxylic acid (TNCA), an analog which is a more potent inhibitor of bone resorption in vitro, for the ability to decrease serum calcium concentration in vivo. In normocalcemic rats on a low calcium diet, TNCA (2 mmol/kg) produced a larger and more prolonged decrease in calcium concentration than TCA. In rats bearing the Walker 256 carcinosarcoma, which became hypercalcemic, TNCA produced a dose-related decrease in serum calcium concentration at 0.3-1.2 mmol/kg. TNCA reduced serum calcium concentration in 4-6 h, and the effects were sustained for up to 72 h. TNCA was effective after oral as well as sc administration. Unlike calcitonin which produced only a transient reduction in serum calcium followed by escape, the effects of TNCA (0.6 mmol/kg) were sustained for 1 week and were accompanied by a decrease in mortality in tumor-bearing animals. We conclude that TNCA is a potent hypocalcemic action which has a rapid and prolonged effect without evidence of escape. This and related compounds should be tested further for use in treatment of hypercalcemia and other states characterized by excessive bone resorption.

Administration, Oral↗
PubMed1977

Compartment analysis of metabolism of chromium(III) in rats of various ages.

The metabolism of chromium(III) was studied in groups of female Wistar rats of various ages (35, 60, and 120 days) after a single intravenous injection of 51CrCl3 in trace amounts. In all the animals, the plasma disappearance curve could be adequately described by a sum of three exponential terms between 0 and 265 h postinjection. A three-compartment mammillary model is proposed that permits the description of Cr(III) metabolism in quantitative terms. The model defines compartment volumes, clearances by exchange, and clearances by excretion. The total excretory clearance is the sum of three components: urinary clearance (fu), fecal clearance (fd), and a residual clearance (fs), corresponding to an apparently irreversible deposition of chromium into long term body reservoirs. The parameters of the model are reported for each age group; when their values are expressed per 100 g of body wt, all the components of the excretory clearance decrease with age. In all cases elimination takes place primarily via the urine and fs accounts for 31-41% of the total excretory clearance. Consistent with the model, 51Cr was found to accumulate with time in several organs such as bone, kidney, spleen, and liver after a single intravenous injection of 51CrCl3.

Aging↗
PubMed1976

Effects of manganese on carcinogenicity and metabolism of nickel subsulfide.

Nickel subsulfide, Ni3S2, alone or combined with manganese or chromium dusts, was administered i.m. to Fischer rats to study the effects of the metals upon Ni3S2 induction of sarcomas at the injection site. The incidence of sarcomas within 2 years after injection of Ni3S2 (1.2 mg) plus manganese (1.0 mg) was 7%, versus 77% in rats that received only Ni3S2 (1.2 mg), and 80% in rats that received Ni3S2 (1.2 mg) plus chromium (1.0 mg) (p less than 0.005). No local sarcomas occurred in rats that received the injection vehicle, or in rats that received manganese or chromium without Ni3S2. Admixture of manganese diminished the solubility of 63Ni3S2 in rat serum, serum ultrafiltrate, or water, in vitro. Admixture of manganese with 63Ni3S2 did not affect the mobilization or excretion of 63Ni in vivo, nor did it alter the acute pathological reactions to Ni3S2. 63Ni concentrations in ultrafiltrates of supernatant fractions of homogenates of injection sites averaged 2.8 (S. D. +/- 0.7) ng/ml at 5 to 6 months after injection of 63Ni3S2 (1.2 mg) plus manganese (1.0 mg), versus 5.4 +/- 2.0 ng/ml after injection of only 63Ni3S2 (1.2 mg) (p less than 0.02). This study demonstrates that admixture of manganese dust and Ni3S2 inhibits Ni3S2 tumorigenesis in rats, and reveals that manganese dust affects the subcellular distribution of 63Ni derived from 63Ni3S2, without influencing 63Ni kinetics as estimated by compartmental analysis.

Animals↗
PubMed1971

[Theoretical note].

Explore the source record for details and available documents.

Analysis of Variance↗
PubMedDate not supplied

Double-blind study of milacemide in hospitalized therapy-resistant patients with epilepsy.

Milacemide, 2-N-pentylaminoacetamide, a glycine prodrug, which readily crosses the blood-brain barrier, has been tested for antiepileptic efficacy and tolerability in 30 patients compared in a double-blind design with 30 patients treated with placebo. All patients continued to receive, without alteration, their previous partly effective medication. All patients presented an average of at least 10 seizures a month during the 6 months preceding the trial with no more than 50% fluctuation. The ratio of seizure frequency in the trial period over the seizure frequency in the baseline period (RSF) was calculated. In the milacemide group, 9 of 29 patients had an RSF less than 0.7 as opposed to 2 of 29 in the placebo group. Although no firm proof of therapeutic efficacy, this and the dramatic improvement of a patient with myoclonus epilepsy indicates that further studies are warranted. This opinion is strengthened if one considers the subgroup of patients aged less than or equal to 25 years in which a statistically significant reduction in seizure frequency was observed with milacemide treatment. The drug was well tolerated.

Acetamides↗