Height associated with different clinical expressions in primary antiphospholipid syndrome female patients.

OBJECTIVE: To compare clinical and laboratory data obtained from patients with primary antiphospholipid syndrome (pAPS) above and below 165 cm of height. PATIENTS AND METHODS: A cross-sectional study with 66 (83.3% female) pAPS patients was performed. Demographic, clinical, drug use, and antiphospholipid antibodies data were evaluated. Patients were subdivided into one of two groups: pAPS ≥ 165 cm and pAPS < 165 cm and compared. RESULTS: In this sample 19/66 (28.8%) of patients were ≥ 165 cm and 47 were < 165 cm of height. Primary APS > 165 cm exhibited a lower frequency of female sex (52.6% vs. 95.7%, p<0.0001) and abortions (0 vs. 34%, p=0.008). A significant higher frequency of antimalarial use was seen in taller patients compared to those < 165 cm (36.8% vs. 14.9%, p=0.04). Furthermore, the analysis of females showed lower mean age (32.3 ± 9.9 vs. 41.3 ± 10.5, p=0.016), higher weight (85.5 ± 25.3 vs. 69.7 ± 17.6 kg, p= 0.023), higher frequency of venous events (100% vs. 66.7%, p=0.025) and lower rate of stroke (10% vs. 44.4%, p=0.043) in taller female than in the smaller. CONCLUSIONS: This study used a systematic design to show that different heights in individuals with pAPS are associated with different diseases' expressions. When analyzing females exclusively, the taller ones were younger, heavier with more venous events, and more minor strokes than the smaller ones.

Can Antidiabetic Drugs Improve Male Reproductive (Dys)Function Associated with Diabetes?

The alarming increase in the number of diabetic patients worldwide raises concerns regarding the impact of the disease on global health, not to mention on social and economic aspects. Furthermore, the association of this complex metabolic disorder with male reproductive impairment is worrying, mainly due to the increasing chances that young individuals, at the apex of their reproductive window, could be affected by the disease, further contributing to the disturbing decline in male fertility worldwide. The cornerstone of diabetes management is glycemic control, proven to be effective in avoiding, minimizing or preventing the appearance or development of disease-related complications. Nonetheless, the possible impact of these therapeutic interventions on male reproductive function is essentially unexplored. To address this issue, we have made a critical assessment of the literature on the effects of several antidiabetic drugs on male reproductive function. While the crucial role of insulin is clear, as shown by the recovery of reproductive impairments in insulin-deficient individuals after treatment, the same clearly does not apply to other antidiabetic strategies. In fact, there is an abundance of controversial reports, possibly related to the various study designs, experimental models and compounds used, which include biguanides, sulfonylureas, meglitinides, thiazolidinediones/glitazones, bile acid sequestrants, amylin mimetics, as well as sodiumglucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP1), α-glucosidase inhibitors and dipeptidyl peptidase 4 (DPP4) inhibitors. These aspects constitute the focus of the current review.

Antidiabetic therapies and male reproductive function: where do we stand?

Diabetes mellitus has been increasing at alarming rates in recent years, thus jeopardizing human health worldwide. Several antidiabetic drugs have been introduced in the market to manage glycemic levels, and proven effective in avoiding, minimizing or preventing the appearance or development of diabetes mellitus-related complications. However, and despite the established association between such pathology and male reproductive dysfunction, the influence of these therapeutic interventions on such topics have been scarcely explored. Importantly, this pathology may contribute toward the global decline in male fertility, giving the increasing preponderance of diabetes mellitus in young men at their reproductive age. Therefore, it is mandatory that the reproductive health of diabetic individuals is maintained during the antidiabetic treatment. With this in mind, we have gathered the available information and made a critical analysis regarding the effects of several antidiabetic drugs on male reproductive function. Unlike insulin, which has a clear and fundamental role on male reproductive function, the other antidiabetic therapies' effects at this level seem incoherent. In fact, studies are highly controversial possibly due to the different experimental study approaches, which, in our opinion, suggests caution when it comes to prescribing such drugs to young diabetic patients. Overall, much is still to be determined and further studies are needed to clarify the safety of these antidiabetic strategies on male reproductive system. Aspects such as the effects of insulin levels variations, consequent of insulin therapy, as well as what will be the impact of the side effect hypoglycemia, common to several therapeutic strategies discussed, on the male reproductive system are still to be addressed.

Mitochondrial Functionality and Chemical Compound Action on Sperm Function.

During the last decade, several studies have shown that mitochondrial parameters, such as integrity, respiratory activity, membrane potential and ROS production are intimately linked with sperm quality. Given the limitations of conventional semen analyses in terms of predicting male fertility, an increasing number of studies are focusing on the characterization of sperm mitochondria in order to more accurately assess sperm functionality. Moreover, mitochondria from several organs, such as the liver, have been described as a powerful screening tool for drug safety, being an easy in vitro model to assess the toxicity of distinct families of compounds. Given that mitochondrial functionality is intimately related to sperm homeostasis, it has become important to understand how compounds, ranging from dietary supplements, environmental pollutants, dependency-inducing drugs to pharmacological agents (such as erectile dysfunction-targeted drugs and male contraceptives) affect sperm mitochondrial function. In this review, we discuss studies describing the effects of various chemical agents on spermatozoa, with particular emphasis on mitochondrial function. From the extensive literature analyzed, we conclude that in some cases the role of sperm mitochondria as putative predictors of sperm functionality is very obvious, while in others further studies are needed to clarify this issue.

In vitro effects of interleukin-4 on interferon-gamma-induced macrophage activation.

Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) have been shown to be secreted by distinct T-helper cell subsets which have different roles in the determination of host resistance to infection. We studied the activity of these two cytokines on effector mechanisms of mouse macrophages. In vitro cultured bone marrow-derived macrophages from C57BL/6 mice were treated with IFN-gamma, IL-4, or a combination of both cytokines and the ability to secrete superoxide or nitrite or to restrict growth of Mycobacterium avium and Toxoplasma gondii was then evaluated. We found that IL-4 could inhibit the priming of macrophages for enhanced superoxide production induced by IFN-gamma although IL-4 when used alone did have some enhancing effect of its own. This effect of IL-4 on IFN-gamma-primed superoxide production was dose dependent and could be observed even if the treatment by IL-4 was done 24 hr after treatment by IFN-gamma. IL-4 did not, however, influence the enhanced production of nitrogen reactive intermediates, the induction of bacteriostatic activity against M. avium, or the restriction of T. gondii by IFN-gamma-treated macrophages, and did not have any effect of its own regarding these latter functions.

[Prevention and treatment of materno-fetal toxoplasmosis]. / Prévention et traitement de la toxoplasmose materno-foetale.

Preventing congenital toxoplasmosis is fundamental, and in France screening tests for primary infection are obligatory for pregnant women. All nonimmunized women should be encouraged to follow good dietary and general health rules until delivery. Nevertheless, the risk of seroconversion does exist but can be detected early through monthly serum tests. Spiramycin as initial treatment of maternal primary infection is an essential step in preventing parasite transmission to the fetus. Fetal antitoxoplasmosis antibodies and indirect signs of congenital abnormalities should be detected early by amniotic fluid and fetal blood tests before echographic evidence confirms the diagnosis. Pyrimethamine-sulfonamide therapy should be undertaken and modulated according to laboratory results in order to prevent or treat any possible fetopathy. Congenital toxoplasmosis can be prevented in utero through biological diagnosis and specific therapy.

[Detection of early humoral response in experimental toxoplasmosis in mice]. / Détection du début de la réponse humorale de la toxoplasmose expérimentale murine.

Experimental infection of mice by Toxoplasma gondii is the best way for antigen production or direct diagnosis. Early serological response from sera and peritoneal exudate of mice infected by T. gondii has been studied. In this report the authors show that specific antibodies (IgM) are found in the serum at 24 hours after intraperitoneal inoculation. Serological methods were unable to detect free antibodies in the peritoneal exudate. Specific antibodies coating the parasite surface were detected by direct immunofluorescence as soon as 48 hours post infection. Biochemical treatment usually used for antigen production (trypsin, pepsin) were unable to destroy this antibodies which where no longer detected after 2 mercapto-ethanol treatment. Control experiments showed that, in these conditions, 2 mercapto-ethanol treatment had no effect on the reactivity of surface antigens with antibodies. Therefore, this results show that checking for specific antibodies absorbed at the surface of T. gondii is a prerequisite of the use of antigen produced in vivo.