Exercise-induced hypoxaemia in master athletes: effects of a polyunsaturated fatty acid diet

Exercise-induced hypoxaemia (EIH) has been associated with an oxygen diffusion limitation. Because polyunsaturated fatty acids (PUFA) administration can modify cell membrane fluidity, we hypothesized that the importance of EIH could be reduced after a 6-week PUFA diet. Resting pulmonary functions and a maximal cycling test were performed before and after the diet, in eight master athletes [48 (SD 6 years)]. The partial pressure. of O₂ in arterial blood (PaO₂), alveolar ventilation ( ) and ideal alveolar-arterial oxygen partial pressure difference (P(A _i–a)O₂) were obtained at each exercise intensity. The extent of EIH at maximal exercise was significantly lower after PUFA [P_aO₂ –17.2 (SEM 1.9) vs –12.9 (SEM 2.2)]. Before PUFA, accounted for 50% of the variance in the fall inP(A _i–a) for intensities below 80% maximal oxygen uptake ( ) andP(A _i–a)O₂ for 60% between 70% and 100% . After PUFA, the reduction in EIH was highly correlated (r ² = 0.85;P < 0.001) to resulting changes inP(A_ii–a)O₂ and resting pulmonary diffusing capacity but not with changes in ideal alveolar partial pressure of oxygen. The improvement in EIH following PUFA could be related to an increase in alveolar-arterial oxygen conductance following improved pulmonary diffusion.     

Combined effects of PPARγ<Subscript>2</Subscript> P12A and PPARα L162V polymorphisms on glucose and insulin homeostasis: the Québec Family Study

Peroxisome proliferator-activated receptors ₂ and are nuclear factors known to be important regulators of lipid and glucose metabolism. Two polymorphisms, namely PPAR₂ P12A and PPAR L162V, were investigated for their individual and interaction effects on glucose and insulin homeostasis. Genotypes were determined in 663 nondiabetic adults participating in the Québec Family Study and who underwent an oral glucose tolerance test (OGTT). The insulin and C-peptide areas under the curve (AUC) following the OGTT were higher in subjects carrying the PPAR V162 allele compared to homozygous for the L162 allele. When subjects were grouped according to both polymorphisms, higher levels of insulin and C-peptide during the OGTT were observed for those carrying the PPAR V162 allele except when they carry at the same time the PPAR₂ A12 allele. Thus, the PPAR₂ A12 allele seems protective against the deleterious effect of the PPAR V162 allele. Furthermore, a significant gene-gene interaction was observed for the acute (0–30 min) (p<0.001) and the total (p=0.05) C-peptide AUC following the OGTT. These results provide evidence of a gene-gene interaction in the regulation of plasma glucose-insulin homeostasis, and emphasize that these interactions need to be taken into account when dissecting the genetic etiology of complex disorders.     

Feasibility and benefits of the ewe as a model for vaginal surgery training

Introduction and hypothesis

The objective was to evaluate the ewe as an animal model for teaching and training in vaginal surgery.

Methods

Twenty-nine postgraduate surgeons attended a training course on vaginal prolapse surgery. After a review of human and sheep anatomy, the participants performed transvaginal meshes, vaginal hysterectomy, SSLF (Richter), and OAS repair in ewes and human cadavers. Participants completed questionnaires on the whole course.

Results

Questionnaires showed the significant superiority of ewes over human cadavers for all items evaluated regarding surgical dissections. Only identification of the sacrospinous ligament and the spine were judged to be similar in ewes and human cadavers. Participants noticed that ewe model is appropriate for vaginal prolapse surgery training for resident and for postgraduate surgeons. Two vaginal hysterectomies were also performed. Operating time, surgery, and anatomy were nearly identical to that of humans. The same conclusions were made while performing sacrospinous ligament fixation (Richter) and obstetric anal sphincter injury repair.

Conclusion

This series indicates that the ewe is a useful animal model for teaching vaginal surgery.

     

Genomics: the next step to elucidate the etiology of calcific aortic valve stenosis

With the current shift toward an older population, calcific aortic valve stenosis (AVS) is likely to become a major societal and economic burden. For many years, AVS was regarded as a degenerative and nonmodifiable process. However, molecular studies unanimously demonstrated that AVS is an actively regulated disorder with several potential therapeutic targets. Many factors are predicted to cause AVS, and an important genetic predisposition is anticipated. In this review, we describe candidate genes and signaling pathways identified by genetic research and incorporate this new knowledge into a more comprehensive picture of factors involved in the pathogenesis of AVS. We also emphasize the need for additional studies to elucidate its complete genetic architecture. Recent advances in genomic research offer a remarkable opportunity to investigate AVS at the most fundamental level. The benefits of these new approaches can be observed in many complex diseases, but the field of AVS is trailing behind. We discuss the future utility of these new genomic approaches to improve our understanding of AVS and to refine the management of patients in terms of diagnosis, prevention, and treatment.     

Bio-distribution study of 1,2-diethylbenzene and its main metabolites by whole-body autoradiography and tissue homogenates

The bio-distribution of the neurotoxic 1,2-diethylbenzene (1,2-DEB) was studied in male Sprague-Dawley rats after intravenous administration of [(14)C] 1,2-DEB (1 mg kg(-1)). The highest concentrations of [(14)C] non-volatile metabolites, determined by whole-body auto-radiography, were in the nasal cavity, ethmoid turbinates and in kidney. Whatever the time after dosing, the [(14)C] concentrations in the cerebrum, cerebellum, spinal cord and lung were lower than those in the blood. In contrast, after killing of batch of administered rats, the [(14)C] concentrations in the brain homogenates were higher than in plasma for 5-15 min. In addition, the [(14)C] concentrations in the lung were higher than in the plasma for 24 h post-dose. Moreover, the concentrations of unchanged 1,2-DEB and one of its metabolites, 1-(2'-ethylphenyl)ethanol (1,2-EPE) in the brain, were higher than in the plasma until 1 h post-dose. The concentrations of 1,2-DEB in the blood cells were tenfold higher than in the plasma. The clearance of unchanged 1,2-DEB in the whole blood and in the blood cells was 6.4 and 3.9 ml min(-1), respectively. The apparent half-life of unchanged 1,2-DEB in plasma is very fast (5 min) which suggests a quick distribution and/or metabolism in liver and/or other tissues such as the lung. In conclusion, unchanged 1,2-DEB has a high affinity for the brain and blood cells and its concentrations in plasma and brain decreased rapidly with time.     

Prevalence of Psychoactive Substance Consumption in People With Obesity

Objective: The aim of this study was to evaluate the prevalence and the kind of psychoactive substances consumed by people with obesity. Methods: Patients were included at their first visit for bariatric surgery. Socio-demographic characteristics, anxiety, depressive disorders and psychoactive substance consumption were assessed. The prevalence of psychoactive substance consumption was compared to that of the general population reported by the French National Institute of Prevention and Health Education. Results: One hundred (100) patients were consecutively recruited: 60 women (mean age 41 ± 14 years) and 40 men (mean age 46 ± 13 years). Sixty-seven percent of subjects consumed alcohol. Consumption rates of cannabis (21% vs. 10%), cocaine (7.0% vs. 0.8%) and amphetamine (6.0% vs. 0.3%) were significantly (p < .0001) higher in people with obesity than in the general population. Conclusions: People with obesity have an excess risk of amphetamine, cocaine and cannabis consumption. This consumption may increase the risk of cardiovascular and psychiatric morbidity and should therefore be detected before surgery.     

Use of human intravenous immunoglobulin in lower motor neuron syndromes

OBJECTIVE: To determine whether patients with the clinical phenotype of multifocal motor neuropathy but without the electrophysiological criteria for conduction block would respond to intravenous immunoglobulin (IVIg). METHODS: Ten patients were selected with a slowly progressive, asymmetric, lower motor neuron disorder, and were treated prospectively with IVIg at a dose of 2g/kg over 5 days. All subjects had neurophysiological testing to look for evidence of conduction block before treatment. Muscle strength was assessed by MRC grades and hand held myometry, measuring pinch and grip strength. A 20% increase in both pinch and grip myometry was considered a positive response. RESULTS: In no patient was conduction block detected. Four of the 10 patients showed a positive response to IVIg, with the best response occurring in two patients who presented with weakness but without severe muscle wasting. Three of the four responders have continued to receive IVIg for a mean period of 17 months (range 15-24 months), with continued effect. The response to IVIg was not related to the presence of anti-GM1 antiganglioside antibodies, but responders had a selective pattern of muscle weakness and normal (>90% predicted) vital capacity. CONCLUSION: The findings suggest that a course of IVIg should be considered in patients with the clinical phenotype of multifocal motor neuropathy but without neurophysiological evidence of conduction block.     

Neuropathy optic glaucomatosa induced by systemic hypertension through activation endothelin-1 signaling pathway in central retinal artery in rats

AIM: To evaluate effect of hypertension on retinal ganglion cell (RGC) apoptosis, intraocular pressure (IOP), and the activation of endothelin-1 (ET-1) signaling pathway in central retinal artery (CRA) in rats. METHODS: The experimental study was performed on 20 male Sprague Dawley rats that were divided into control group, and hypertension groups. The hypertension was induced by subcutaneous deoxycorticoacetate (DOCA) 10 mg/kg twice a week and administered 0.9% NaCl solution daily for 2, 6, and 10wk. Blood pressure (BP) was measured using animal BP analyzer. IOP was measured by handheld tonometry. Retinal tissue preparations by paraffin blocks were made after enucleation. The expression of ET-1, eNOS, ET-1 receptor A (ETRA), ET-1 receptor B (ETRB), and phosphorylated myosin light chain kinase (MLCK), and caldesmon (CaD) in CRA and RGC apoptosis were evaluated through immunofluorescent staining method then observed using laser scanning confocal microscopy. RESULTS: BP significantly increased in all of the hypertension groups compared to control (P=0.001). Peak IOP elevation (7.78±4.14 mm Hg) and RGC apoptosis (576.15±33.28 Au) occurred on 2wk of hypertension. ET-1 expression (1238.6±55.1 Au) and eNOS expression (2814.2±70.7 Au) were found highest in 2wk of hypertension, although the ratio of ET-1/eNOS decreased since 2wk. ETRA reached peak expression in 10wk of hypertension (1219.4±6.3 Au), while ETRB significantly increased only in 2 weeks group (1069.2±9.6 Au). The highest MLCK expression (1190.09±58.32 Au), CaD (1670.28±18.36 Au) were also found in 2wk of hypertension. CONCLUSION: Hypertension effects to activation of ET-1 signaling pathway significantly in CRA, elevation of IOP, and RGC apoptosis. The highest value was achieved at 2wk, which is the development phase of hypertension.