Sex differences in the pharmacokinetics of pioglitazone in rats

Clinical studies have suggested that pioglitazone, an insulin sensitizer, has a stronger effect in women than in men. To determine the sex difference in the pharmacokinetics of pioglitazone, we examined the plasma and white adipose tissue levels of pioglitazone and its active metabolites (M-II, M-III and M-IV) in male and female rats treated with a single or repeated oral administration of pioglitazone (10 mg/kg). The AUCs of pioglitazone (149.6+/-22.6 vs. 103.3+/-14.0 microg.h/ml; P<0.01), M-III (31.4+/-8.1 vs. 20.2+/-4.7 microg.h/ml; P<0.05) and M-IV (41.9+/-15.5 vs. 14.1+/-1.6 microg.h/ml; P<0.01) were larger in female rats than in male rats, but the levels of M-II were similar. Any of the compounds did not accumulate in plasma after repeated administration. According to kinetic model analysis, the apparent elimination rate of pioglitazone and the formation rate of M-II were faster in male rats than in female rats. No significant sex difference was found in the tissue-to-plasma concentration ratios of pioglitazone or its active metabolites in white adipose tissue. These results suggest that there are sex differences in the plasma levels of pioglitazone and some of its active metabolites and that those differences are reflected in differences in white adipose tissue levels.     

Bioavailability of seaweed iodine in human beings.

The major procedure used to correct iodine deficiency is the universal salt iodization by addition of iodide or iodate to salt with an iodine content varying from 7 to 100 mg/kg of salt depending on the country legislation. As an important fraction of consumers in the world prefers natural products over artificial ones, we investigated the industrial feasibility of naturally iodized salt using seaweed as source of iodine. We report the results of the iodine bioavailability in healthy subjects from two seaweeds: Laminaria hyperborea and Gracilaria verrucosa selected due to their high level in iodine as a mineral or an organic form and low levels of heavy metals. As a control we studied in a normal man the bioavailability of pure mineral iodine such as potassium iodide which was excellent i.e. 96.4% and of pure organic iodine such as monoiodotyrosine which was a little lower i.e. 80.0%. Iodine bioavailability from these two seaweeds was studied in nine normal subjects from Marseille (France) which is an iodine sufficient area based on a median urinary iodine level of 137 microg/day and innine normal subjects from Brussels (Belgium) who present a mild iodine deficiency with a value of 73 microg/day. The iodine bioavailability of Gracilaria verrucosa is better than for Laminaria hyperborea (101% versus 90% in Marseille, t=0.812, NS; 85% versus 61.5% in Brussels, t = 2.486, p = 0.024, S*). The urinary excretion of iodine is lower in Brussels than in Marseille for the same seaweed because part of the iodine is stored in the thyroid (101% versus 85% for Gracilaria verrucosa, t = 1.010, NS; 90% versus 61.5% for Laminaria hyperborea, t = 3.879, p= 0.001, S***).     

On the metabolism of prostaglandin E1 administered intravenously to human volunteers.

We have demonstrated recently the formation of a biologically active metabolite of prostaglandin (PG) E1, 13,14-dihydro-PGE1, during intravenous infusions of PGE1 in patients with peripheral arterial occlusive disease. We have now investigated the levels of the immediate precursor of 13,14-dihydro-PGE1, the biologically inactive 15-keto-13,14-dihydro-PGE1, during intravenous administration of 20 micrograms, 40 micrograms or 80 micrograms PGE1 over a period of 60 min to human volunteers. It was found that levels of 15-keto-13,14-dihydro-PGE1, but not those of PGE1 itself, increased in a dose-dependent manner. Thus, increased formation of 13,14-dihydro-PGE1 from 15-keto-13,14-dihydro-PGE1 with increasing doses of PGE1 can be expected to occur. It remains to be investigated, to which extent formation of small amounts of 13,14-dihydro-PGE1 during intravenous infusion of PGE1 could contribute to the therapeutic effects of PGE1 in patients with peripheral arterial occlusive disease.     

Chronic toxicity of rare-earth elements on human beings

Blood analyses for rare-earth element (REE)-high background regions in South Jiangxi show that the population averages of many of the biochemical indices deviate markedly from normal values in the normal region. These deviations are thought to be caused by prolonged intake of REE through food chains in view of that the toxicity of other harmful metals such as Pb and Cd can be neglected because of their insignificant amounts in the environment. In comparison with the normal region, blood biochemical indices abnormal in the REE-high regions are manifested as low total serum protein (TSP), albumin, β-globulin, glutamic pyruvic transitanase, serium triglycerides, and immunoglobulin, but high cholesterol. These deviations may be related to the REE concentration and composition of food chains, and are sex dependent. Certain blood indices (such as TSP) of different age groups in the LREE-high region indicate that the influence of REE on males is a one-way irreversible process, whereas females show a strong ability of restoration.     

Mechanism of the light flashes induced in human beings by ionizing particles

Exposure of a dark adapted human eye to weak proton beams of different energy for which the yield of Cerenkov radiation varies by approximately 50 times, the other characteristics being virtually the same, showed that this radiation was mainly responsible for visual sensation.     

Use of a physiological model of gentamicin pharmacokinetics for individual dosage of the antibiotic]

A new approach to fixing the initial doses of gentamicin (GM) for its intramuscular administration (the most commonly used anyway) is discussed. The approach is based on the physiological model reproducing the individual patterns of GM concentration change in patient's blood. Such parameters of the model as blood flow velocity and actual average volume of specific tissues as well as the tissue to the blood partition coefficient (Kp) are constant. They were used to calculate the volume of distribution in the body specific organs (Vs). The apparent distribution volume (Vd) and total clearance (Cl) are individual parameters. The Vd value was calculated individually for every particular patient depending on the body weight by the known equations. The difference between Vd and Vs was used to calculate the individual Kp for the organs and tissues which were not specially examined. When calculating Cl of GM, the patient's sex, age, weight and creatinine concentrations were taken into account. To evaluate the local velocity of blood flow after antibiotic intramuscular administration, it was important to consider the patient's sex and age. The approach was used to reproduce the individual patterns of GM concentration change after the initial administration of the antibiotic, 80 mg, to 19 male patients (age range, 21 to 73 years; weight range, 50 to 94 kg; blood creatinine concentration, 0.4 to 1.6 mg/dl). The GM concentrations attained with the use of the model were afterwards compared to the data on FPIA. (TDx, Abbott) by measuring the GM concentrations in the blood of the patients 0.5, 1, 5 and 7 hours after the administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

The embryonic stem cell lottery and the cannibalization of human beings

One objection to embryonic stem (ES) cell research is that it 'cannibalizes' human beings, that is, kills some human beings to benefit others. I grant for argument's sake that the embryo is a person. Nonetheless, killing it may be justified. I show this through the Embryonic Stem Cell Lottery. Whether killing a person is justified depends on: (1) whether innocent people at risk of being killed for ES cell research also stand to benefit from the research and (2) whether their overall chances of living are higher in a world in which killing and ES cell research is conducted. I call this kind of killing 'risk reductive.'