Non-invasive methods for embryo selection.

With the widespread use of assisted reproduction, a simple and practical method for embryo selection is needed to optimize the chances of pregnancy while diminishing the incidence of multiple pregnancy and its accompanying problems. Many non-invasive methods for embryo selection have been proposed and some are more promising than others. This review summarizes these methods and attempts to evaluate them in the light of the best currently available evidence and to find out whether any of them is ripe for replacing or supplementing the time-honored method of morphological assessment.

Religious aspects of assisted reproduction

Human response to new developments regarding birth, death, marriage and divorce is largely shaped by religious beliefs. When assisted reproduction was introduced into medical practice in the last quarter of the twentieth century, it was fiercely attacked by some religious groups and highly welcomed by others. Today, assisted reproduction is accepted in nearly all its forms by Judaism, Hinduism and Buddhism, although most Orthodox Jews refuse third party involvement. On the contrary assisted reproduction is totally unacceptable to Roman Catholicism, while Protestants, Anglicans, Coptic Christians and Sunni Muslims accept most of its forms, which do not involve gamete or embryo donation. Orthodox Christians are less strict than Catholic Christians but still refuse third party involvement. Interestingly, in contrast to Sunni Islam, Shi'a Islam accepts gamete donation and has made provisions to institutionalize it. Chinese culture is strongly influenced by Confucianism, which accepts all forms of assisted reproduction that do not involve third parties. Other communities follow the law of the land, which is usually dictated by the religious group(s) that make(s) the majority of that specific community. The debate will certainly continue as long as new developments arise in the ever-evolving field of assisted reproduction.

Does ovulation induction increase the risk of gynecological cancer?

The risk of developing gynaecological cancer following ovulation induction therapy in infertile patients is not easy to determine due to many confounding factors. These include the fact that infertility in itself is a known risk factor for some of these cancers, that these patients are subjected to increased surveillance compared to the general population and that the drugs used for ovulation induction are sometimes used in combination. Notwithstanding these limitations, most of the studies have not confirmed a link between these drugs and invasive ovarian cancers, although some studies have suggested that the risk of borderline ovarian tumors may be increased. Investigations regarding breast cancer risk have produced inconsistent results and more information on the subject is warranted. On the contrary, many studies suggest that drugs used for ovulation induction may increase the risk of uterine cancers. More large well-designed studies are still needed to further clarify the effects on cancer risk of these drugs and will allow more in-depth subgroup analysis based on both patient and disease characteristics.

GABA(B) receptor-mediated selective peripheral analgesia by the non-proteinogenic amino acid, isovaline.

Peripherally restricted analgesics are desirable to avoid central nervous system (CNS) side effects of opioids. Nonsteroidal anti-inflammatory drugs produce peripheral analgesia but have significant toxicity. GABA(B) receptors represent peripheral targets for analgesia but selective GABA(B) agonists like baclofen cross the blood-brain barrier. Recently, we found that the CNS-impermeant amino acid, isovaline, produces analgesia without apparent CNS effects. On observing that isovaline has GABA(B) activity in brain slices, we examined the hypothesis that isovaline produces peripheral analgesia mediated by GABA(B) receptors. We compared the peripheral analgesic and CNS effect profiles of isovaline, baclofen, and GABA (a CNS-impermeant, unselective GABA(B) agonist). All three amino acids attenuated allodynia induced by prostaglandin E2 injection into the mouse hindpaw and tested with von Frey filaments. The antiallodynic actions of isovaline, baclofen, and GABA were blocked by the GABA(B) antagonist, CGP52432, and potentiated by the GABA(B) modulator, CGP7930. We measured Behavioural Hyperactivity Scores and temperature change as indicators of GABAergic action in the CNS. ED(95) doses of isovaline and GABA produced no CNS effects while baclofen produced substantial sedation and hypothermia. In a mouse model of osteoarthritis, isovaline restored performance during forced exercise to baseline values. Immunohistochemical staining of cutaneous layers of the analgesic test site demonstrated co-localization of GABA(B1) and GABA(B2) receptor subunits on fine nerve endings and keratinocytes. Isovaline represents a new class of peripherally restricted analgesics without CNS effects, mediated by cutaneous GABA(B) receptors.

Exercise restores endothelial function independently of weight loss or hyperglycaemic status in db/db mice.

AIMS/HYPOTHESIS: Exercise ameliorates oxidative stress-mediated diabetic vascular endothelial dysfunction through poorly defined mechanisms. We hypothesised that, in addition to improving metabolic parameters, upregulation of antioxidants such as superoxide dismutase (SOD) mediates exercise-induced reductions of oxidative stress and increased nitric oxide (NO) bioavailability, and also restores vasodilatation. METHODS: Type 2 diabetic db/db and normoglycaemic wild-type mice were exercised at moderate intensity for 1 h a day for 7 weeks, leading to a 10% body weight loss. Sedentary animals or those undergoing a low-intensity exercise regimen causing non-significant weight loss were also used. We examined aortic endothelial cell function, NO bioavailability and various biomarkers of oxidative stress. RESULTS: Moderate-intensity exercise lowered body weight, increased mitochondrial manganese SOD (MnSOD) and both total and phosphorylated (Ser1177) endothelial nitric oxide synthase (eNOS) protein production; it also reduced whole-body (plasma 8-isoprostane) and tissue oxidative stress (nitrotyrosine immunostaining or protein carbonyl levels in the aorta). Low-intensity exercise did not alter body weight; however, it upregulated cytosolic Cu/Zn-SOD instead of MnSOD, and still demonstrated all the above benefits in the db/db aorta. Importantly, both exercise protocols improved endothelial-dependent vasodilatation and NO bioavailability without altering hyperglycaemic status in db/db mice. CONCLUSIONS/INTERPRETATION: Exercise reverses diabetic vascular endothelial dysfunction independently of improvements in body weight or hyperglycaemia. Our data suggest that upregulation of eNOS and specific SOD isoforms could play important roles in improving NO bioavailability, as well as in reversing endothelial dysfunction in type 2 diabetes patients through lifestyle modifications in the management of diabetes.

In vivo effect of chloramphenicol and thiamphenicol on some enzymes of normal mouse liver.

Chloramphenicol a potent inhibitor of bacterial and some mammalian cell protein synthesis, was administered i.p. to a group of mice for 6 consecutive days. Another group of animals was treated similarly with thiamphenicol and a third group served as control. The effects of the two antibiotics on the activity of some liver enzymes; the two pyridoxal 5-phosphate dependent enzymes, kynurenine hydrolase and kynurenine amino-transferase; pyridoxal phosphokinase; beta-glucuronidase and acid ribonuclease were determined. Chloramphenicol and thiamphenicol decreased significantly the activities of kynurenine hydrolase, beta-glucuronidase and acid ribonuclease and both drugs increased the activity of pyridoxal phosphokinase significantly. Their effect on kynurenine amino-transferase was different, chloramphenicol decreased while thiamphenicol increased the enzyme activity. Results are discussed and possible explanations suggested.