Influence of Reoperations on Long-Term Quality of Life After Restrictive Procedures: A Prospective Study

Quality of life improves after bariatric surgery. However, long-term results and the influence of reoperations are not well known. A prospective quality of life assessment before, 1 and 7 years after laparoscopic adjustable gastric banding (LAGB) and vertical banded gastroplasty (VBG) was performed in order to determine the influence of reoperations during follow-up. One hundred patients were included in the study. Fifty patients underwent VBG and 50 LAGB. Patients completed the quality of life questionnaires prior to surgery and two times during follow-up. Health-related quality of life (HRQoL) questionnaires included the Nottingham Health Profile I and II and the Sickness Impact Profile 68. Follow-up was 84% with a mean duration of 84 months (7 years). During follow-up, 65% of VBG patients underwent conversion to Roux-en-Y gastric bypass while 44% of LAGB patients underwent a reoperation or conversion. One year after the procedure, nearly all quality-of-life parameters significantly improved. After 7 years, the Nottingham Health Profile (NHP)-I domain “physical ability”, the NHP-II and the SIP-68 domains “mobility control”, “social behavior”, and “mobility range” were still significantly improved in both groups. The domains “emotional reaction”, “social isolation” (NHP-I), and “emotional stability” (SIP-68) remained significantly improved in the VBG group while this was true for the domain “energy level” (NHP-I) in the LAGB group. Both the type of procedure and reoperations during follow-up were not of significant influence on the HRQoL results. Weight loss and decrease in comorbidities were the only significant factors influencing quality of life. Restrictive bariatric surgery improves quality of life. Although results are most impressive 1 year after surgery, the improvement remains significant after long-term follow-up. Postoperative quality of life is mainly dependent on weight loss and decrease in comorbidities and not on the type of procedure or surgical complications

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

High salt diet modulates vascular response in A2AAR+/+ and A2AAR−/− mice: role of sEH, PPARγ, and KATP channels

This study aims to investigate the signaling mechanism involved in HS-induced modulation of adenosine-mediated vascular tone in the presence or absence of adenosine A2A receptor (A2AAR). We hypothesized that HS-induced enhanced vascular relaxation through A2AAR and epoxyeicosatrienoic acid (EETs) is dependent on peroxisome proliferator-activated receptor gamma (PPARγ) and ATP-sensitive potassium channels (KATP channels) in A2AAR+/+ mice, while HS-induced vascular contraction to adenosine is dependent on soluble epoxide hydrolase (sEH) that degrades EETs in A2AAR−/− mice. Organ bath and Western blot techniques were conducted in HS (4 % NaCl) and normal salt (NS, 0.45 % NaCl)-fed A2AAR+/+ and A2AAR−/− mouse aorta. We found that enhanced vasodilation to A2AAR agonist, CGS 21680, in HS-fed A2AAR+/+ mice was blocked by PPARγ antagonist (T0070907) and KATP channel blocker (Glibenclamide). Also, sEH inhibitor (AUDA)-dependent vascular relaxation was mitigated by PPARγ antagonist. PPARγ agonist (Rosiglitazone)-induced relaxation in HS-A2AAR+/+ mice was attenuated by KATP channel blocker. Conversely, HS-induced contraction in A2AAR−/− mice was attenuated by sEH inhibitor. Overall, findings from this study that implicates the contribution of EETs, PPARγ and KATP channels downstream of A2AAR to mediate enhanced vascular relaxation in response to HS diet while, role of sEH in mediating vascular contraction in HS-fed A2AAR−/− mice.SCOPUS: ar.jinfo:eu-repo/semantics/publishe