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Biomedical subjects

G Gabriels

Publications and source records attributed to G Gabriels.

6 recordsLinked to original sources
PubMed2000

Impaired flow-mediated vasodilation of the brachial artery in patients with primary hyperparathyroidism improves after parathyroidectomy.

OBJECTIVE: The endothelium is a newly recognised target tissue of parathyroid hormone (PTH). It is not clear whether hyperparathyroidism affects endothelial function and whether parathyroidectomy (Ptx) has an influence on arterial vessel wall properties. We studied brachial flow-mediated vasodilation (FMD) and brachial and carotid intima-media thickness (IMT) in patients with primary hyperparathyroidism (pHPT) before and after Ptx and in healthy controls. METHODS: 19 patients with pHPT (mean+SEM, age 45+/-4.7 years, PTH 238+/-52 ng/l) were studied. Diabetes, hypertension and vascular disease were excluded. Twenty healthy volunteers matched for age, sex and blood pressure served as controls. Enddiastolic diameter, FMD and nitroglycerine-induced (NMD) dilation of the brachial artery were measured by a multigate pulsed doppler system (echo-tracking), IMT was determined using automatic analysis of the M-line signal. Healthy volunteers where studied on one occasion, patients were studied at baseline and 6 months after Ptx. RESULTS: Six months after Ptx PTH had decreased to normal, blood pressure levels remained unchanged. Endothelium dependent FMD at baseline was impaired in patients compared to controls (4.7+/-1.2 vs. 18.2+/-3.7%, P<0.01), however, FMD improved significantly after Ptx (16.7+/-3.0%, P<0.01). Nitroglycerine-induced dilation, IMT and artery diameter were not different between groups and did not change after Ptx. CONCLUSIONS: Impaired endothelium dependent vasodilation in patients with primary hyperparathyroidism improves after successful parathyroidectomy. Endothelial dysfunction associated with primary hyperparathyroidism occurs without detectable structural wall alterations of the brachial artery and appears therefore to be an early and reversible arterial alteration.

Adult↗
PubMed1999

Recent bioequivalence studies on fixed-dose combination anti-tuberculosis drug formulations available on the global market.

SETTING: Concern has been expressed about the bioavailability of rifampicin in some fixed-dose combination (FDC) anti-tuberculosis formulations. OBJECTIVE: To evaluate the relative bioavailability of rifampicin in various FDC formulations currently in use in tuberculosis control programmes in the global market. DESIGN: A two-period randomised crossover bioequivalence study in healthy male volunteers, with a 1 week washout period between treatments. Plasma rifampicin concentrations were measured at 0, 1, 2, 4, 6, 8 and 12 hours after each drug administration. RESULTS: The AUC0-8, AUC0-12 and Cmax for rifampicin in seven of 10 FDC formulations was not found to be bioequivalent to the reference administered as loose (separate) formulations. This was confirmed using parametric and non-parametric statistical methods. CONCLUSIONS: The poor relative bioavailability of rifampicin from some FDCs has been documented. The implications for tuberculosis programmes are extremely serious and warrant urgent attention.

Antibiotics, Antitubercular↗
PubMed1999

The development of a standardised screening protocol for the in vivo assessment of rifampicin bioavailability.

SETTING: The prerequisite for in vivo bioavailability testing of rifampicin in fixed-dose combination (FDC) formulations is widely accepted. However, many smaller drug regulatory authorities and drug manufacturers have difficulty implementing costly and cumbersome testing procedures. OBJECTIVE: To test whether a simplified blood sampling schedule can be used for the determination of drug bioequivalence in randomised, single dose, crossover studies of FDCs and appropriate reference formulations. METHOD: The results of three bioavailability and bioequivalence studies of different rifampicin-containing FDCs were analysed. The relationship between the number of time points employed and precision of estimated relative bioavailability was explored. The relative bioavailabilities of the drug components in the test FDCs were calculated using maximal concentration and area under the curve estimates based on an extended blood sampling schedule of up to 15 time points over 48 hours, and a contracted sampling scheme with only six blood samples over 8 hours. RESULTS: Estimates of relative bioavailability calculated using the contracted blood sampling protocol were closely similar to those derived using the extended sampling schedules. CONCLUSION: Considerable cost and convenience benefits can be gained by using the contracted sampling schedule with only a minor reduction in the precision of the estimation of relative rifampicin bioavailability.

Adolescent↗
PubMed1996

Tunicamycin potentiates drug cytotoxicity and vincristine retention in multidrug resistant cell lines.

Tunicamycin (TM), an inhibitor of glycoprotein processing, was investigated for its potential to reverse the multiple drug resistance (MDR) phenotype. When TM was added in vitro to drug-resistant NIH-3T3-MDR and KB-8-5-11 cells, they developed an increased sensitivity to doxorubicin, epirubicin, vincristine and colchicine. Similarly, the sensitivity of NIH-3T3-MDR cells to cisplatin was also enhanced by TM. In the presence of TM, drug-sensitive NIH-3T3-parental cells exhibited greater susceptibility to the toxic effects of doxorubicin, epirubicin, vincristine (marginally significant), and colchicine, but not to cisplatin. Tunicamycin-treated drug-sensitive KB-3-1 cells showed an increased response to vincristine, but not to the other anticancer drugs. Pretreatment with TM inhibited glycoprotein synthesis in all the cell lines. Neither prior exposure to, nor co-incubation with TM, influenced the uptake of vincristine (VCR) in the various cell lines. However, NIH-3T3-MDR cells accumulated less VCR than their drug-sensitive controls and also exhibited reduced efflux of the drug when treated with TM. There were no significant differences in the levels of intracellular VCR uptake between drug-sensitive KB-3-1 and KB-8-5-11 cells. Tunicamycin increased intracellular VCR retention in KB-8-5-11 and NIH-3T3-MDR cells, but not in NIH-3T3-parental cells. However, drug-sensitive KB-3-1 cells expressed reduced VCR retention in response to TM exposure, indicating that correlations between VCR toxicity and its retention in the presence of TM should be made with caution. The results suggest that the enhancement of intracellular VCR retention in MDR cells lines caused by TM is likely to be the result of inhibition of VCR efflux. Inhibition of glycoprotein synthesis during TM exposure may account for the changes in VCR efflux and retention observed in the MDR cell lines. The enhancement of cisplatin cytotoxicity in NIH-3T3-MDR cells after exposure to TM is an interesting observation, since it is generally believed that agents which modify the MDR phenotype do not show a sensitising effect to cisplatin. These findings may have applications in the reversal of drug resistance.

Antineoplastic Agents↗
PubMed1996

Pseudoephedrine is without ergogenic effects during prolonged exercise.

This study was designed to measure whether a single dose of 120 mg pseudoephedrine ingested 120 min before exercise influences performance during 1 h of high-intensity exercise. The effects of exercise on urinary excretion of the drug were also studied. Ten healthy male cyclists were tested on two occasions, separated by at least 7 days, by using a randomly assigned, double-blind, placebo-controlled, crossover design. Exercise performance was tested during a 40-km trial on a laboratory cycle ergometer, and skeletal muscle function was measured during isometric contractions. On a third occasion, subjects ingested 120 mg pseudoephedrine but did not exercise [control (C)]. Pseudoephedrine did not influence either time trial performance [drug (D) vs. placebo: 58.1 +/- 1.4 (SE) vs. 58.7 +/- 1.5 min] or isometric muscle function. Urinary pseudoephedrine concentrations were significantly increased 1 h after exercise (D vs. C: 114.3 +/- 27.2 vs. 35.4 +/- 13.1 micrograms/ml; P < 0.05). Peak plasma pseudoephedrine concentrations (P < 0.05) but not time taken to reach peak plasma concentrations or the area under the plasma pseudoephedrine concentration vs. time curve was significantly increased in the total group with exercise (D vs. C). In three subjects, plasma pseudoephedrine concentrations were not influenced by exercise. Only these subjects showed increased urinary pseudoephedrine excretion during exercise. We conclude that a single therapeutic dose of pseudoephedrine did not have a measurable ergogenic effect during high-intensity exercise of 1-h duration, but plasma drug concentrations and urinary excretion were altered by exercise. These findings have practical relevance to doping control regulations in international sporting competitions.

Adult↗