Role of Vascular Oxidative Stress in Obesity and Metabolic Syndrome

Obesity is associated with vascular diseases that are often attributed to vascular oxidative stress. We tested the hypothesis that vascular oxidative stress could induce obesity. We previously developed mice that overexpress p22phox in vascular smooth muscle, tg^sm/p22phox, which have increased vascular ROS production. At baseline, tg^sm/p22phox mice have a modest increase in body weight. With high-fat feeding, tg^sm/p22phox mice developed exaggerated obesity and increased fat mass. Body weight increased from 32.16 ± 2.34 g to 43.03 ± 1.44 g in tg^sm/p22phox mice (vs. 30.81 ± 0.71 g to 37.89 ± 1.16 g in the WT mice). This was associated with development of glucose intolerance, reduced HDL cholesterol, and increased levels of leptin and MCP-1. Tg^sm/p22phox mice displayed impaired spontaneous activity and increased mitochondrial ROS production and mitochondrial dysfunction in skeletal muscle. In mice with vascular smooth muscle–targeted deletion of p22phox (p22phox^loxp/loxp/tg^smmhc/cre mice), high-fat feeding did not induce weight gain or leptin resistance. These mice also had reduced T-cell infiltration of perivascular fat. In conclusion, these data indicate that vascular oxidative stress induces obesity and metabolic syndrome, accompanied by and likely due to exercise intolerance, vascular inflammation, and augmented adipogenesis. These data indicate that vascular ROS may play a causal role in the development of obesity and metabolic syndrome.     

Changes in Bone Mineral Density of Both Proximal Femurs after Total Knee Arthroplasty

Background

This study investigated the effects of total knee arthroplasty (TKA) on bone mineral density (BMD) of the proximal femur in patients who underwent the procedure.

Methods

Forty-eight patients scheduled to undergo unilateral TKA because of primary knee osteoarthritis were included in this study, which was conducted at a medical center between October 2006 and October 2009. In these 48 patients, 96 hips were evaluated. Measurement of BMD was performed preoperatively and one month, three months, six months, and one year after unilateral TKA. Repeated measured analysis of variance and paired t-tests for comparison of two repeated samples were used to compare differences between time points (preoperation, one, three, six, and 12 months) and between the operative and nonoperative sides.

Results

Preoperatively, BMD of the femoral neck, trochanter, and total hip on the operative side were lower than on the nonoperative side; however, there was no statistical difference. BMD of both femoral neck areas was significantly lower than preoperative BMD at one month and three months after TKA. BMD of both trochanter areas was significantly lower than preoperative BMD at one month and three months after TKA. BMD of both total hips was significantly lower than preoperative BMD at three months after TKA. However, no statistical differences of changes in BMD were observed between the operative and nonoperative sides at each measurement time.

Conclusions

According to our results, TKA was found to affect both proximal femurs during the acute period. However, TKA did not affect a change in BMD of the proximal femur during one year postoperative.     

Social Branding to Decrease Smoking Among Young Adults in Bars

Objectives. We evaluated a Social Branding antitobacco intervention for “hipster” young adults that was implemented between 2008 and 2011 in San Diego, California.Methods. We conducted repeated cross-sectional surveys of random samples of young adults going to bars at baseline and over a 3-year follow-up. We used multinomial logistic regression to evaluate changes in daily smoking, nondaily smoking, and binge drinking, controlling for demographic characteristics, alcohol use, advertising receptivity, trend sensitivity, and tobacco-related attitudes.Results. During the intervention, current (past 30 day) smoking decreased from 57% (baseline) to 48% (at follow-up 3; P = .002), and daily smoking decreased from 22% to 15% (P < .001). There were significant interactions between hipster affiliation and alcohol use on smoking. Among hipster binge drinkers, the odds of daily smoking (odds ratio [OR] = 0.44; 95% confidence interval [CI] = 0.30, 0.63) and nondaily smoking (OR = 0.57; 95% CI = 0.42, 0.77) decreased significantly at follow-up 3. Binge drinking also decreased significantly at follow-up 3 (OR = 0.64; 95% CI = 0.53, 0.78).Conclusions. Social Branding campaigns are a promising strategy to decrease smoking in young adult bar patrons.Tobacco companies1 and public health authorities2–5 recognize young adulthood as a critical time when experimenters either quit or transition to regular tobacco use. Young adults are also aspirational role models for youths.1,6,7 Tobacco companies devote considerable resources to reaching young adults to encourage tobacco use,1,8–11 and young adults have a high prevalence of smoking.12 In California in 2011, young adults had the highest smoking prevalence of any age group, and the Department of Health estimated that 32% of California smokers started smoking between the ages of 18 and 26 years.13 Although they are more likely to intend to quit and successfully quit than older adults,14–17 young adults are less likely to receive assistance with smoking cessation.18,19 Although there are few proven interventions to discourage young adult smoking,20 cessation before age 30 years avoids virtually all of the long-term adverse health effects of smoking.21Tobacco companies have a long history of using bars and nightclubs to reach young adults and to encourage smoking.1,6,9–11,22–24 Bar attendance and exposure to tobacco bar marketing is strongly associated with smoking.25 The 1998 Master Settlement Agreement and Food and Drug Administration regulations that limit tobacco advertising to youths, explicitly permit tobacco marketing in “adult only” venues, including bars and nightclubs.26,27Aggressive tobacco marketing may actually be more intensive in smoke-free bars: a 2010 study of college students attending bars found that students in the community with a smoke-free bar law were more likely to be approached by tobacco marketers, offered free gifts, and to take free gifts for themselves than in communities without a smoke-free bar law.28 Bars and nightclubs also attract young adults who are more likely to exhibit personality traits such as sensation seeking,29 increasing their risk30 independently of receptivity to tobacco advertising; tobacco promotional messages resonate with these personality traits.8,31 Tobacco marketing campaigns are tailored to specific segments of the population defined by psychographics (e.g., values, attitudes, shared interests, such as tastes in music and fashion, and friend groups) and demographic criteria, and they aim to create positive smoker images, identities, and social norms for smoking.1,8 Tobacco marketing campaigns also focus on young adult trendsetters to leverage peer influence to promote smoking.6,10In contrast to the tobacco companies’ efforts, most young adult health interventions take place in colleges or health centers rather than social environments.32–39 Bars and nightclub venues represent an opportunity to reach those at highest risk for long-term smoking morbidity and mortality.40 We evaluated the effectiveness of an intervention to decrease cigarette smoking by countering tobacco industry marketing strategies targeting young adults attending bars and nightclubs in the San Diego, California, “hipster” scene. Because tobacco and alcohol use are strongly linked,41,42 we also examined the effects of the intervention on alcohol use and among binge drinkers. We found a significant decrease in smoking in the community where the intervention took place, including significant decreases among nondaily smokers and binge drinkers, as well as a significant decrease in binge drinking.     

Low and high linear energy transfer radiation sensitization of HCC cells by metformin

The purpose of this study was to investigate the efficacy of metformin as a radiosensitizer for use in combination therapy for human hepatocellular carcinoma (HCC). Three human HCC cell lines (Huh7, HepG2, Hep3B) and a normal human hepatocyte cell line were treated with metformin alone or with radiation followed by metformin. In vitro tests were evaluated by clonogenic survival assay, FACS analysis, western blotting, immunofluorescence and comet assay. Metformin significantly enhanced radiation efficacy under high and low Linear Energy Transfer (LET) radiation conditions in vitro. In combination with radiation, metformin abrogated G2/M arrest and increased the cell population in the sub-G1 phase and the ROS level, ultimately increasing HCC cellular apoptosis. Metformin inhibits the repair of DNA damage caused by radiation. The radiosensitizing effects of metformin are much higher in neutron (high LET)-irradiated cell lines than in γ (low LET)-irradiated cell lines. Metformin only had a moderate effect in normal hepatocytes. Metformin enhances the radiosensitivity of HCC, suggesting it may have clinical utility in combination cancer treatment with high-LET radiation.     

Effects of the Type of Intraoperative Fluid in Living Donor Kidney Transplantation: A Single-Center Retrospective Cohort Study

PurposePerioperative fluid management in kidney transplant recipients is crucial to supporting the fluid, acid-base, and electrolyte balance required for graft perfusion. However, the choice of intraoperative crystalloids in kidney transplantation remains controversial. We conducted a single-center retrospective cohort study to evaluate the impact of intraoperative fluids on acid-base and electrolyte balance and graft outcomes.Materials and MethodsWe included 282 living donor kidney transplant recipients from January 2010 to December 2017. Patients were classified into two groups based on the type of intraoperative crystalloids used (157 patients in the half saline group and 125 patients in the balanced crystalloid solutions group, Plasma-lyte).ResultsCompared with the half saline group, the Plasma-lyte group showed less metabolic acidosis and hyponatremia during surgery. Hyperkalemia incidence was not significantly different between the two groups. Changes in postoperative graft function assessed by blood urea nitrogen and creatinine were significantly different between the two groups. Patients in the Plasma-lyte group exhibited consistently higher glomerular filtration rates than those in the half saline group at 1 month and 1 year after transplantation after adjusting for demographic differences.ConclusionIntraoperative Plasma-lyte can lead to more favorable results in terms of acid-base balance during kidney transplantation. Patients who received Plasma-lyte showed superior postoperative graft function at 1 month and 1 year after transplantation. Further studies are needed to evaluate the superiority of intraoperative Plasma-lyte over other types of crystalloids in relation to graft outcomes.