Effects of 4-deoxypyridoxine on the isovolumic perfused rat heart: influence of oxygenation and glucose availability

The study was performed with isolated perfused isovolumic rat hearts. After a 40 min stabilization period, the effect of 4-deoxypyridoxine (DOP) 10(-5) M was studied with 3 Glc concentrations: 0, 3.3 and 11 mM. DOP was perfused during a 20 min normoxic or anoxic period followed by 40 min of normal perfusion. During normoxia with 11 mM Glc, DOP decreased the contracture observed in the control group. With 0 mM Glc, DOP improved developed pressure and dP/dt+ without a decrease in glycogen stores. During anoxia followed by reoxygenation, a partial protection towards CK release was observed with DOP (3.3 mM Glc). Intracellular PLP levels were higher in the 11 mM Glc group than in the other groups with and without DOP, and DOP with 11 mM Glc increased PLP levels (DOP N2 vs. DOP O2). Glycogen stores increased with 11 mM Glc without DOP (O2 vs. N2), whereas they decreased with DOP without Glc (DOP N2 vs. N2). DOP could improve the yield in glycogenolysis in normoxia and might activate mitochondrial anaerobic metabolism during anoxia.     

Risk of thromboembolism in relation to an in-vitro fertilization programme: three case reports

Severe thrombotic events following ovarian stimulation for in-vitrofertilization (IVF) procedures in three women are reported.None of these patients presented any concomitant clinical signof ovarian hyperstimulation syndrome. Coagulation inhibitorswere in the normal range but cardiovascular risk factors werepresent. It is postulated that early thrombosis could be favouredby high endogenous plasma oestrogen concentrations subsequentto ovarian stimulation when associated with another risk factor.Our data are discussed in relation to previous publications.It is suggested that risk factors must be considered individuallybefore each IVF attempt. In patients at high risk, clinicalmanagement of the post-transfer period is recommended.     

Methylazoxymethanol acetate does not fully block cell genesis in the young and aged dentate gyrus

During adulthood, new neurons are continuously added to the mammalian dentate gyrus (DG). An increasing number of studies have correlated changes in rates of dentate neurogenesis with memory abilities. One study based on subchronic treatment with the toxin methylazoxymethanol acetate (MAM) has provided causal evidence that neurogenesis is involved in hippocampal-dependent trace conditioning. In contrast, spatial learning is not impaired following MAM treatment. We hypothesized that this was due to the small residual number of new cells produced following MAM treatment. In the present experiment, we attempted to achieve a higher level of reduction of adult-generated cells following MAM treatment in young and aged rats. We found only a partial reduction of adult-generated cells in the DG. More importantly, independently of the age of the animals, MAM treatment at a dose necessary to reduce neurogenesis altered the overall health of the animals. In conclusion, the behavioural results obtained following subchronic treatment with high doses of MAM in adulthood must be interpreted with extreme caution.     

Implication of corticosteroid receptors in the regulation of hippocampal structural plasticity

The dentate gyrus is one of the few areas of the adult brain that continues to produce neurons and to express the embryonic polysialylated isoforms of neuronal cell adhesion molecules (PSA-NCAM). The stress hormone corticosterone exerts a complex modulation on neurogenesis and PSA-NCAM, and previous studies have shown that mature granule cells require corticosterone for their survival. Thus, the aim of our work was to investigate the respective role of the different corticosteroid receptors on these three parameters in adrenalectomized rats. It was found that treatment with a low dose of the mineralocorticoid receptor agonist, aldosterone, prevents only the adrenalectomy-induced increase in cell death. Treatment with a higher dose of aldosterone normalized cell proliferation whereas PSA-NCAM expression was normalized only by treatment with the glucocorticoid receptor agonist, RU 28362. It is concluded that stimulation of the mineralocorticoid receptor is sufficient to mediate the effects of corticosterone on neurogenesis and to protect mature cells from cell death whereas stimulation of the glucocorticoid receptor is necessary to modulate PSA-NCAM expression.     

Concentration of benzydamine in vaginal mucosa following local application: an experimental and clinical study

The results of an experimental and clinical study on the benzydamine binding and distribution in vaginal mucosa are presented, employing benzydamine solution for gynaecological use. When applied first to rats, the mean amount of the drug in their vaginal mucosa became 3.65 +/- 2.99 micrograms/g of fresh tissue with a significant difference between control and treated animals, without detectable amounts in the plasma. When applied to humans, the mean amount of benzydamine assayed in 17 specimens of vaginal mucosa was 9.72 +/- 6.24 micrograms/g. It was greater than the range of animal anti-inflammatory concentration (2-8 micrograms/g) established by pharmacological studies on this drug and justified the local benefits from benzydamine treatment of vaginal inflammation. Benzydamine assayed in seven volunteers with healthy vaginas showed that the drug cannot be detected in the plasma.     

Pharmacological findings on cetiedil

The molecule of cetiedil (Stratène) has strong papaverine-like and weak atropine-like properties. It brings about peripheral vasodilation at doses which do not affect arterial blood pressure, heart beat and cardiac efficacy; this new drug increases the activity of beta-adrenergic stimulants. There may be different hypotheses to explain the therapeutic effect of cetiedil; beside its papaverinic and synergistic beta-stimulant properties, it increases the haemodynamic coefficient, plays a role in the process of membrane Ca++ exchange and inhibits phosphodiesterase and platelet aggregation.     

Contribution of liver, skin and skeletal muscle to whole-body protein synthesis in the young lamb

1. Protein fractional synthesis rate (FSR) was measured in some major tissues and in the whole body of six 1-week-old sucking lambs by a large injection of L-[3H]valine. 2. Upper estimates of tissue protein FSR (%/d), assuming that the tissue-homogenate free-valine specific radioactivity defined that of valyl tRNA, were 115.0 in liver, 24.1 in skin, 22.9 in the white M. tensor fasciae latae, 21.6 in the red M. diaphragma and 19.6 in the remainder (exsanguinated whole body without liver and gastrointestinal tract) of lambs. 3. Absolute synthesis rates (ASR) of tissue protein were 17, 19 and 42 g/d in the liver, skin and skeletal muscle respectively, and 112 g/d in the remainder. The ASR of whole-body protein, derived from the tissue values, was 146 g/d, i.e. 33 g/d per kg body-weight. The calculated whole-body protein FSR was 23.9%/d. 4. The relative percentage contribution of liver, skin and skeletal muscle to whole-body protein synthesis was 11.7, 13.1, and 29.0. 5. We concluded that tissue protein FSR in lambs were in exactly the same decreasing order, from visceral tissues to skeletal muscles, as observed in rats. The ovine FSR estimates and the partitioning of protein synthesis between tissues were in the same range as values recently obtained by flooding-dose experiments in immature rats, piglets, and even in chicks. These findings suggest that inter-species differences are rather limited.