Connexins participate in the initiation and progression of atherosclerosis

Connexins are members of a large family of transmembrane proteins that form hemichannels or gap junctions. These channels allow the exchange of ions and small metabolites between the cytosol and extracellular space or between neighboring cells. Connexins are important in vascular physiology; they support radial and longitudinal cell-to-cell communication in the vascular wall. Four connexins are expressed in the vascular wall: Cx37, Cx40, Cx43, and Cx45. Their expression is not uniform in all blood vessels and varies with vascular territory and species. Significant changes in the expression pattern of vascular connexins have been described during the development of atherosclerosis, a progressive inflammatory disease. In this review, we provide an overview of (1) the tools used to study the involvement of connexins in atherosclerosis, (2) the participation of connexins in atherogenesis, (3) the increasing interest of a polymorphism in the human connexin37 gene as marker of cardiovascular disease, and (4) the possible therapeutic implications of connexin

Female population perception of conventional laparoscopy, transumbilical LESS, and transvaginal NOTES for cholecystectomy

Background: Recent population survey has shown a preference for transumbilical laparoendoscopic single-site surgery (U-LESS) compared with natural orifice transluminal endoscopic surgery (NOTES) for cholecystectomy, assuming similar surgical risk. This study was designed to evaluate the perception and preference of women regarding conventional laparoscopy, U-LESS, and transvaginal NOTES (TV-NOTES) with particular interest to access perception. Methods: An anonymous questionnaire on laparoscopic, U-LESS, and TV-NOTES cholecystectomy, without regards to risks or advantages, was given to female medical/paramedical staff (n=100), patients (n=100), and the general population (n=100). Women participants (median age, 35 (range, 16-79) years) were queried about preference, perception of the different accesses, and personal informations. Of the respondents, 54% had children, 79% had stable relationships, and 96% were sexually active (vaginal intercourse). Results: With similar operative risk, 87% preferred U-LESS, 4% TV-NOTES and 8% laparoscopy. LESS/NOTES choice was influenced by a desire of improved cosmetics (82%) and lower pain (44%). 96% had worries regarding transvaginal access, among them: dyspareunia (68%), decreased sensibility during intercourse (43%), refuse of short-term sexual abstinence (40%), and infertility (23%). Transumbilical access evocated worries in 35%: umbilical pain (19%), postoperative umbilical sensibility (15%), and incisional hernia (11%). Postoperative intercourse abstinence after TV-NOTES evocated worries in 76% (defined as 3weeks in survey): feel less attractive (40%), less feminine (32%), tension with their intimate (35%), lover non-acceptation (20%), possible abortion of new relationship (26%), and feel less comfortable socially (16%). Conclusions: The high acceptation rate for U-LESS approach compared with TV-NOTES may be related to fears regarding postoperative sexuality and fertility. The importance of temporary postoperative sexual abstinence (vaginal intercourse) is high and may be difficult to influence. Future research on TV-NOTES should focus on the access risk to be able to scientifically reassure our patients. For now, U-LESS seems to be favor compared with TV-NOTES for cholecystectomy in female patient

Enzymatic glycosylation of Ellagic acid

Ellagic acid is a natural biomolecule with several biological propertiesi such as anti-oxidant activity. However the poor solubility of this compound limits its bioavailability and its potential for pharmaceutical or cosmetic application.ii It’s well-known that glycosylation can significantly improve the physicochemical and biological properties of small molecules.iii Enzymatic glycosylation of this compound would be a solution to access a more soluble ellagic acid through a sustainable and environmentally friendly process. Glucansucrases, that use sucrose as donor substrate to transfer a glucose unit, are highly promising catalysts to glycosylate high valuated biomolecules.iv Please click Additional Files below to see the full abstract

Single Port Access Laparoscopic Cholecystectomy (with video)

Background: Single port access (SPA) surgery is a rapidly evolving field due to the complexity of NOTES (natural orifice translumenal endoscopic surgery). SPA combines the cosmetic advantage of NOTES and possibility to perform surgical procedure with standard laparoscopic instruments. We report a technique of umbilical SPA cholecystectomy using standard laparoscopic instruments and complying with conventional surgical principle and technique of minimally invasive cholecystectomy. Methods: Preliminary, prospective experience of SPA cholecystectomy in 11 patients (median age, 46 (range, 27-63) years) scheduled for cholecystectomy was evaluated. Diagnoses for cholecystectomy were: symptomatic gallbladder lithiasis (n=7), previous acute cholecystitis (n=3), and biliary pancreatitis (n=1). Results: SPA cholecystectomy was feasible in all patients (median body mass index, 24 (range, 20-34) kg/m2) who were scheduled for preliminary experience using conventional laparoscopic instruments. Median operative time was 52 (range, 40-77) minutes. Intraoperative cholangiography was performed in all patients, except one, and was considered normal. No peroperative or postoperative complications were recorded. Median hospital stay was less than 24 h. Conclusions: SPA cholecystectomy is feasible and seems to be safe when performed by experienced laparoscopic surgeons using standard laparoscopic instrumentation. SPA cholecystectomy may be safer than the NOTES approach at this time. It has to be determined whether this approach would benefit patients, other than cosmesis, compared with standard laparoscopic cholecystectom

Population perception of surgical safety and body image trauma: a plea for scarless surgery?

Background: Laparoendoscopic single-site surgery (LESS) and natural orifice translumenal endoscopic surgery (NOTES) are prospected as the future of minimally invasive surgery. While scarless surgery (NOTES and LESS) is gaining increasing popularity, perception of these approaches should be investigated. Methods: An anonymous questionnaire describing laparoscopy, LESS, and NOTES was given to medical staff (n=120), paramedical staff (n=100), surgical patients (n=100), and the general population (n=100). The survey participants (median age, 37 years; range, 18-81years) were queried about their expectations for surgical treatment and their approach preference. Results: The first concern of the survey responders was the risk of surgical complications (92%). When asked about the respective importance of surgical safety, cure, and cosmetics, cure was placed first by 74%, safety by 33%, and cosmetics by 3%. These results were not influenced by sex, age, prior surgery or endoscopy, or education. When operative risk was similar, 90% of the participants preferred a scarless approach (75% preferred LESS and 15% preferred NOTES) to laparoscopy. The scarless approach preference was significantly higher among the younger participants (age <40years; p=0.026), whereas sex showed no influence. The LESS preference was significantly higher among patients and the general population (86%) than among medical (67%) and paramedical (70%) staffs (p<0.001). A decreasing trend of preference for LESS and NOTES was observed with increased procedural risks. Conclusion: Although cure and safety remain the main concern, the population has a favorable perception of scarless surgery, even in the case of increased procedural risk, with LESS favored over NOTES. Such a popular adoption of scarless surgery should warrant the promotion of further research, technological innovations, and the establishment of surgeon training to improve its safet

The natural cardioprotective particle HDL modulates connexin43 gap junction channels

Aims High-density lipoprotein (HDL) is known for its cardioprotective properties independent from its cholesterol transport activity. These properties are mediated by activation of kinases such as protein kinase C (PKC). Connexin43 (Cx43) is a gap junction protein present in ventricular cardiomyocytes. PKC-dependent phosphorylation modifies Cx43 gap junction channel properties and is involved in cardioprotection. We hypothesized that cardioprotective properties of HDL may be mediated in part by affecting Cx43 gap junction channels. Methods and results Neonatal rat cardiomyocytes were treated with HDL and Cx43 phosphorylation was evaluated by western blotting and immunofluorescence. We found that HDL promoted phosphorylation of Cx43 with a maximal induction at 5 min, which was inhibited by pre-treatment with various PKC inhibitors. Sphingosine-1-phosphate (S1P), a component of HDL, induced effects that were similar to those of HDL. These compounds significantly reduced diffusion of fluorescent dye among cardiomyocytes (∼50%) which could be prevented by PKC inhibition. As observed during optical recordings of transmembrane voltage, HDL and S1P depressed impulse conduction only minimally (<5%). Moreover, 5 min of HDL and S1P treatment at the onset of reperfusion significantly reduced infarct size (∼50%) in response to 30 min ischaemia in ex vivo experiments. Conclusion Short-term treatment with HDL or S1P induces phosphorylation of Cx43 by a PKC-dependent pathway. HDL-induced phosphorylation of Cx43 reduced the diffusion of large tracer molecules between cells, whereas impulse conduction was maintained. Moreover, 5 min treatment with HDL confers cardioprotection against ischaemia/reperfusion injury. These results link Cx43 for the first time to the short-term cardioprotective effects of HD

Daily reoxygenation decreases myocardial injury and improves post-ischaemic recovery after chronic hypoxia

Objective: In contrast to the clinical evidence, experimental studies showed that chronic hypoxia (CH) confers a certain degree of protection against ischaemia-reperfusion damage. We studied the effects of daily reoxygenation during CH (CHReox) on hearts exposed to ischaemia-reperfusion. We also separated the intrinsic effects on the myocardium of CH and CHReox from those related to circulatory and nervous factors. Methods: Fifty-one Sprague-Dawley rats were maintained for 15 days under CH (10% O2) or CHReox (10% O2+1hday−1 exposure to air). Normoxic (N, 21% O2) rats were the control. The animals were randomly assigned to one of the three following protocols: (1) protocol A: hearts (n=7 per group) were subjected to 30-min occlusion of the left anterior descending (LAD) coronary artery followed by 3-h reperfusion, with measurement of the injury by tetrazolium staining; (2) protocol B: the end-diastolic pressure (EDP) and left ventricular developed pressure×heart rate (LVDP×HR) were measured in Langendorff-perfused isolated hearts (n=5 per group) during 30-min global ischaemia and 45-min reperfusion; and (3) protocol C: hearts (n=5 per group) were frozen for the determination of levels of endothelial nitric oxide synthase (eNOS) by Western blotting. Results: CHReox hearts displayed greater phosphorylation of the eNOS and enhanced plasma level of nitrates and nitrites in comparison to CH hearts (P≪0.0001, Bonferroni's post-test). The infarct size was greater in CH than in N hearts (P≪0.0001, Bonferroni's post-test) while it was reduced in CHReox in comparison to CH and N hearts (P≪0.0001). At the end of reperfusion, EDP was higher in CH than CHReox and N hearts (P=0.01, Bonferroni's post-test) while LVDP×HR was higher in CHReox and N than in CH hearts (P=0.03, Bonferroni's post-test). Conclusions: Exposure to CH results in impairment of myocardial tolerance to ischaemia-reperfusion, greater injury and reduced recovery of performance, in agreement with clinical evidence. Infarct size, diastolic contracture and myocardial performance have been reduced, respectively, by 63%, 64% and 151% with daily reoxygenation compared with chronic hypoxia by accelerating intrinsic adaptive change

Impact of HLA matching on the outcome of simultaneous pancreas-kidney transplantation

Background. Simultaneous pancreas-kidney (SPK) transplantation has become the therapy of choice for type 1 diabetic patients with end-stage renal disease. The current analysis examined the impact of human leukocyte antigen (HLA) matching on graft outcome following SPK transplantation. The study population was obtained from patients enrolled in the Euro-SPK 001 study. Methods. The effect of HLA matching on graft function and survival was assessed in 180 SPK recipients in whom complete donor-recipient HLA data were available. A group of 45 patients with 0-3 HLA mismatches (MM) was compared with a group of 135 patients with 4-6 MM. Results. There were no differences in 3-year kidney, pancreas or patient survival between the 0-3 and 4-6 MM groups. Biological parameters of kidney and pancreas graft function were similar in both groups. Significantly more patients with 0-3 MM (66%) were rejection-free at 3 years than was the case among those with 4-6 MM (41%; P = 0.003). The relative risk of acute rejection was 2.6 times higher among patients with 4-6 MM than among those with 0-3 MM. Conclusions. There was no evidence that HLA matching was associated with improved kidney or pancreas survival. However, a higher rate of acute rejection was observed with poor HLA match, which may impact long-term surviva