Publications

ObjectivesTherapies less invasive than surgery and more effective than lifestyle and pharmacotherapy are needed to contend with the obesity epidemic. Intragastric balloons (IGBs) are a minimally invasive endoscopic weight loss method recently approved for use in the US. The purpose of the study is to assess the effect of IGBs on metabolic outcomes associated with obesity.MethodsMEDLINE, Embase, and Cochrane Database were searched through July 2016. Dual extraction and quality assessment of studies using Cochrane risk of bias tool were performed independently by two authors. Primary outcomes included the change from baseline in metabolic parameters. Secondary outcomes included resolution and/or improvement in metabolic co-morbidities and association with baseline parameters.Results10 randomized controlled trials (RCT) and 30 observational studies including 5,668 subjects were analyzed. There was moderate-quality evidence for improvement in most metabolic parameters in subjects assigned to IGB therapy as compared to conventional non-surgical therapy in RCTs: mean difference (MD) in fasting glucose change: -12.7 mg/dl (95% confidence interval (CI) -21.5, -4); MD in triglycerides: -19 mg/dl (95% CI -42, 3.5); MD in waist circumference: -4.1 cm (95% CI -6.9, -1.4); MD in diastolic blood pressure: -2.9 mm Hg (95% CI -4.1, -1.8). The odds ratio for diabetes resolution after IGB therapy was 1.4 (95% CI 1.3, 1.6). The rate of serious adverse events was 1.3%.ConclusionsIGBs are more effective than diet in improving obesity-related metabolic risk factors with a low rate of adverse effects, however the strength of the evidence is limited given the small number of participants and lack of long-term follow-up.

Hyperalgesic priming, a model of pain chronification in the rat, is mediated by ryanodine receptor-dependent calcium release. Although ryanodine induces priming in both sexes, females are 5 orders of magnitude more sensitive, by an estrogen receptor α (EsRα)-dependent mechanism. An inositol 1,4,5-triphosphate (IP) receptor inhibitor prevented the induction of priming by ryanodine. For IP induced priming, females were also more sensitive. IP-induced priming was prevented by pretreatment with inhibitors of the sarcoendoplasmic reticulum calcium ATPase and ryanodine receptor. Antisense to EsRα prevented the induction of priming by low-dose IP in females. The induction of priming by an EsRα agonist was ryanodine receptor-dependent and prevented by the IP antagonist. Thus, an EsRα-dependent bidirectional interaction between endoplasmic reticulum IP and ryanodine receptor-mediated calcium signaling is present in the induction of hyperalgesic priming, in females. In cultured male DRG neurons, IP (100 μm) potentiated depolarization-induced transients produced by extracellular application of high-potassium solution (20 mm, K20), in nociceptors incubated with β-estradiol. This potentiation of depolarization-induced calcium transients was blocked by the IP antagonist, and not observed in the absence of IP IP potentiation was also blocked by ryanodine receptor antagonist. The application of ryanodine (2 nm), instead of IP, also potentiated K20-induced calcium transients in the presence of β-estradiol, in an IP receptor-dependent manner. Our results point to an EsRα-dependent, reciprocal interaction between IP and ryanodine receptors that contributes to sex differences in hyperalgesic priming. The present study demonstrates a mechanism that plays a role in the marked sexual dimorphism observed in a model of the transition to chronic pain, hyperalgesic priming. This mechanism involves a reciprocal interaction between the endoplasmic reticulum receptors, IP and ryanodine, in the induction of priming, regulated by estrogen receptor α in the nociceptor of female rats. The presence of this signaling pathway modulating the susceptibility of nociceptors to develop plasticity may contribute to our understanding of sex differences observed clinically in chronic pain syndromes.