The atheroprotective role of fucoidan involves the reduction of foam cell formation by altering cholesterol flux-associated factors in macrophages.

Atherosclerosis is characterized by the accumulation of lipid-laden cells in the arterial walls, resulting from dysregulation of cholesterol homeostasis in the macrophage, triggered by oxidized low-density lipoprotein (oxLDL). Previous studies have shown that fucoidan, a sulfated polysaccharide from brown seaweeds, has several atheroprotective activities, however, the mechanism of fucoidan protection is not fully understood. Thus, we investigated the effect of fucoidan on atherogenesis in apolipoprotein E-deficient (ApoE-/-) mice, on oxLDL uptake by macrophages, and on the expression of the flux-associated scavenger receptors by macrophages. Also, we examined the absorption and biodistribution of orally administered fucoidan. ApoE-/- mice fed on a cholesterol-rich diet supplemented with 1% fucoidan showed reduced dyslipidemia and atherosclerosis. Fucoidan was detected in blood and peripheral tissue after gavage, suggesting that it can exert direct systemic effects. In vitro, fucoidan reduced macrophage oxLDL uptake, which resulted in lower foam cell formation. This effect was associated with downregulation of the cholesterol influx-associated scavenger receptor (SR)-A expression, and upregulation of the cholesterol efflux-associated SR-B1 expression. In conclusion, fucoidan prevented oxLDL-mediated foam cell formation in macrophages by downregulating SR-A1/2 and by up-regulating SR-B1.

Protease-activated receptor 2 enhances innate and inflammatory mechanisms induced by lipopolysaccharide in macrophages from C57BL/6 mice.

OBJECTIVE: This study was conducted to investigate the effects of the synthetic PAR2 agonist peptide (PAR2-AP) SLIGRL-NH2 on LPS-induced inflammatory mechanisms in peritoneal macrophages. METHODS: Peritoneal macrophages obtained from C57BL/6 mice were incubated with PAR2-AP and/or LPS, and the phagocytosis of zymosan fluorescein isothiocyanate (FITC) particles; nitric oxide (NO), reactive oxygen species (ROS), and cytokine production; and inducible NO synthase (iNOS) expression in macrophages co-cultured with PAR-2-AP/LPS were evaluated. RESULTS: Co-incubation of macrophages with PAR2AP (30 µM)/LPS (100 ng/mL) enhanced LPS-induced phagocytosis; production of NO, ROS, and the pro-inflammatory cytokines interleukin (IL)-1ß, tumour necrosis factor (TNF)-α, IL-6, and C-C motif chemokine ligand (CCL)2; and iNOS expression and impaired the release of the anti-inflammatory cytokine IL-10 after 4 h of co-stimulation. In addition, PAR2AP increased the LPS-induced translocation of the p65 subunit of the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB) and reduced the expression of inhibitor of NF-κB. CONCLUSION: This study provides evidence of a role for PAR2 in macrophage response triggered by LPS enhancing the phagocytic activity and NO, ROS, and cytokine production, resulting in the initial and adequate macrophage response required for their innate response mechanisms.

d-Limonene Ameliorates Myocardial Infarction Injury by Reducing Reactive Oxygen Species and Cell Apoptosis in a Murine Model.

Myocardial infarction (MI) leads to high mortality, and pharmacological or percutaneous primary interventions do not significantly inhibit ischemia/reperfusion injuries, particularly those caused by oxidative stress. Recently, research groups have evaluated several naturally occurring antioxidant compounds for possible use as therapeutic alternatives to traditional treatments. Studies have demonstrated that d-limonene (DL), a monoterpene of citrus fruits, possesses antioxidant and cardiovascular properties. Thus, this work sought to elucidate the mechanisms of protection of DL in an isoproterenol-induced murine MI model. It was observed that DL (10 µmol) attenuated 40% of the ST elevation, reduced the infarct area, prevented histological alterations, abolished completely oxidative stress damage, restored superoxide dismutase activity, and suppressed pro-apoptotic enzymes. In conclusion, the present study demonstrated that DL produces cardioprotective effects from isoproterenol-induced myocardial infarction in Swiss mice through suppression of apoptosis.

Predictors of Successful Weight Loss in Extremely Obese Individuals Undergoing Roux-en-Y Gastric Bypass Surgery.

Background: Roux-en-Y gastric bypass (RYGB) is a standard treatment for severe obesity, but some patients do not achieve the expected success in weight loss. The aim of this study was to evaluate possible predictors of weight loss after RYGB. Methods: Sixty-three patients were included. Pre- and postoperative data were collected from medical records, including comorbidities, anthropometry, energy/macronutrient intake, and physical activity level (PAL). Variants in the brain-derived neurotrophic factor (BDNF; rs6265) and lysophospholipase like 1 (LYPLAL1; rs4846567) genes were investigated. Excess weight loss (EWL) >50% was considered to be successful weight loss (SWL). Logistic regression models were used to verify predictor variables. Results: Participants' median preoperative body mass index (BMI) was 53 kg/m2 (interquartile range, 46 to 58). At 12 and 24 months after surgery, EWL was 63% and 67%, and the failure rate was 19% and 16%, respectively. The individuals with insufficient weight loss (IWL) after 12 months had higher preoperative weight, BMI, and overweight. At 24 months, lowest frequency of individuals with SWL in the first year was found in the IWL group. No significant differences were found between the groups in dietary intake and PAL. In the logistic regression, high initial BMI was a predictor of the worst response in both periods, and high initial total weight loss was a predictor of a better response at 24 months. The polymorphism analysis did not show differences between groups in either gene. Conclusion: Lower preoperative BMI and greater weight loss at 12 months were predictors of SWL after RYGB.

Capsaicin Improves Systemic Inflammation, Atherosclerosis, and Macrophage-Derived Foam Cells by Stimulating PPAR Gamma and TRPV1 Receptors.

BACKGROUND: Capsaicin, a bioactive compound found in peppers, is recognized for its anti-inflammatory, antioxidant, and anti-lipidemic properties. This study aimed to evaluate the effects of capsaicin on atherosclerosis progression. METHODS: Apolipoprotein E knockout mice and their C57BL/6 controls were utilized to assess blood lipid profile, inflammatory status, and atherosclerotic lesions. We also examined the influence of capsaicin on cholesterol influx and efflux, and the role of TRPV1 and PPARγ signaling pathways in bone marrow-derived macrophages. RESULTS: Capsaicin treatment reduced weight gain, visceral adiposity, blood triglycerides, and total and non-HDL cholesterol. These improvements were associated with a reduction in atherosclerotic lesions in the aorta and carotid. Capsaicin also improved hepatic oxidative and inflammatory status. Systemic inflammation was also reduced, as indicated by reduced leukocyte rolling and adhesion on the mesenteric plexus. Capsaicin decreased foam cell formation by reducing cholesterol influx through scavenger receptor A and increasing cholesterol efflux via ATP-binding cassette transporter A1, an effect primarily linked to TRPV1 activation. CONCLUSIONS: These findings underscore the potential of capsaicin as a promising agent for atherosclerosis prevention, highlighting its comprehensive role in modulating lipid metabolism, foam cell formation, and inflammatory responses.

Atorvastatin attenuates intestinal mucositis induced by 5-fluorouracil in mice by modulating the epithelial barrier and inflammatory response.

Chemotherapy-induced intestinal mucositis is a major side effect of cancer treatment. Statins are 3-hydroxy-3-methyl glutaryl coenzyme reductase inhibitors used to treat hypercholesterolemia and atherosclerotic diseases. Recent studies have demonstrated that atorvastatin (ATV) has antioxidant, anti-inflammatory, and resulting from the regulation of different molecular pathways. In the present study, we investigated the effects of ATV on intestinal homeostasis in 5-fluorouracil (5-FU)-induced mucositis. Our results showed that ATV protected the intestinal mucosa from epithelial damage caused by 5-FU mainly due to inflammatory infiltrate and intestinal permeability reduction, downregulation of inflammatory markers, such as Tlr4, MyD88, NF-κB, Tnf-a, Il1ß, and Il6 dose-dependent. ATV also improved epithelial barrier function by upregulating the mRNA transcript levels of mucin 2 (MUC2), and ZO-1 and occludin tight junction proteins. The results suggest that the ATV anti-inflammatory and protective effects on 5-FU-induced mice mucositis involve the inhibition of the TLR4/MYD88/NPRL3/NF-κB, iNos, and caspase 3.

Higher atherogenic risk in schoolchildren is associated with MTMR9 rs2293855 gene polymorphism and genetic score.

Childhood dyslipidaemia is associated with the occurrence of cardiovascular diseases in adulthood, so evaluating whether an individual has a genetic predisposition to this pathology is of great importance for early action of prevention and treatment. This study aimed to evaluate the association between the FTO (rs9939609), MC4R (rs17782313) and MTMR9 (rs2293855) polymorphisms, the obesity-related genetic risk score and atherogenic risk in Brazilian children. This is a cross-sectional study conducted in 544 children aged 4-9 years in the city of Viçosa, Minas Gerais state, Brazil. The single nucleotide polymorphisms rs9939609, rs17782313 and rs2293855, were identified by the system TaqMan SNP genotyping and the obesity-related genetic risk score was determined. The lipid profile (serum total cholesterol [TC], high density lipoprotein [HDL] cholesterol, low density lipoprotein [LDL] cholesterol, triglycerides) was analysed and the atherogenic indices (Castelli I and II indices), atherogenic coefficient (AC), lipoprotein combined index (LCI) and plasma atherogenic index (PAI) were calculated. A semi-structured questionnaire was applied, obtaining data on the sociodemographic, economic and lifestyle characteristics of the children. Weight and height measurements were performed in all children, and body composition was evaluated by Dual-Energy X-ray Absorptiometry (DXA). 55.5% of the sample had dyslipidaemia, while 28.5% of the sample had at least one polymorphism and 2.2% had three polymorphisms. Children with the AG/AA genotypes in the rs2293855 polymorphism had lower HDL cholesterol levels and higher TC/HDL cholesterol, LDL/HDL cholesterol ratios and AC. Those with one or more polymorphisms (rs9939609, rs17782313 and rs2293855) in the genetic risk score had lower HDL cholesterol levels and higher TC/HDL cholesterol ratios, AC, LCI and PAI. In conclusion, the risk allele of the rs2293855 polymorphism and a higher obesity-related genetic risk score were positively associated with higher atherogenic risk in Brazilian children.

Obesity with no metabolic syndrome and adipose tissue expansion based solely on risk factors and inflammatory marker of coronary heart disease in premenopausal women.

The objective of this study was to analyze whether obese women with no metabolic syndrome (MetS) have increased cardiometabolic risk compared to non-obese women and to observe the correlations between adiposity and coronary heart disease (CHD) risk factors in metabolically healthy women. 20-40 year old non-obese (n=41), obese with no MetS (n=30) and obese with MetS (n=28) women were studied. Lipid profile, blood pressure, CHD family history, physical inactivity, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, interleukin-1beta and tumor necrosis factor-alpha were analyzed. A subset of obese (13) and non-obese (33) women with no major components of MetS (except waist circumference) were further compared. Obese women with no MetS and non-obese women presented a similar metabolic profile that was statistically different from those seen in obese women with MetS. The number of obese women with no MetS and non-obese women presenting two or more risk factors (23.3 and 19.5%, respectively) or presenting high Framingham Risk Score (6.7 and 2.4%, respectively) were also similar. The only pro inflammatory protein correlated to waist circumference was hs-CRP. These data suggest that obesity with no MetS induce a CHD risk comparable to the risk seen in non-obese women. However, when women with no major components of MetS alone were considered, adiposity was positively correlated to blood pressure and hs-CRP. Although CHD risk of obese women with no MetS is closer to non-obese women, adipose tissue expansion was positively correlated to blood pressure and hs-CRP that are important risk factors for CHD.

OxLDL induces membrane structure rearrangement leading to biomechanics alteration and migration deficiency in macrophage.

Cholesterol sequestration from plasma membrane has been shown to induce lipid packing disruption, causing actin cytoskeleton reorganization and polymerization, increasing cell stiffness and inducing lysosomal exocytosis in non-professional phagocytes. Similarly, oxidized form of low-density lipoprotein (oxLDL) has also been shown to disrupt lipid organization and packing in endothelial cells, leading to biomechanics alterations that interfere with membrane injury and repair. For macrophages, much is known about oxLDL effects in cell activation, cytokine production and foam cell formation. However, little is known about its impact in the organization of macrophage membrane structured domains and cellular mechanics, the focus of the present study. Treatment of bone marrow-derived macrophages (BMDM) with oxLDL not only altered membrane structure, and potentially the distribution of raft domains, but also induced actin rearrangement, diffuse integrin distribution and cell shrinkage, similarly to observed upon treatment of these cells with MßCD. Those alterations led to decreased migration efficiency. For both treatments, higher co-localization of actin cytoskeleton and GM1 was observed, indicating a similar mechanism of action involving raft-like domain dynamics. Lastly, like MßCD treatment, oxLDL also induced lysosomal spreading in BMDM. We propose that OxLDL induced re-organization of membrane/cytoskeleton complex in macrophages can be attributed to the insertion of oxysterols into the membrane, which lead to changes in lipid organization and disruption of membrane structure, similar to the effect of cholesterol depletion by MßCD treatment. These results indicate that oxLDL can induce physical alterations in the complex membrane/cytoskeleton of macrophages, leading to significant biomechanical changes that compromise cell behavior.

Lower paraoxonase 1 paraoxonase activity is associated with a worse prognosis in patients with non-ST-segment elevation myocardial infarction in long-term follow-up.

BACKGROUND: Acute coronary syndrome (ACS) is one of the main manifestations of coronary artery disease, with a higher prevalence and worst prognosis. Oxidative stress is important in atherosclerosis and ACS, and paraoxonase 1 (PON1) is directly related to reducing the effects of oxidative stress on lipoproteins. The present study evaluated the prognostic value of PON1 activity in patients with non-ST-segment elevation ACS [non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina (UA)], included in the ERICO study. METHODS: PON1 paraoxonase activity was determined in serum samples from 485 patients collected on admission. The prognostic value in the follow-up of up to 5 years was evaluated according to cutoff points established by tertiles. Kaplan-Meier curves and Cox regression were used for the analysis of all-cause mortality and cardiovascular mortality. RESULTS: The sample consisted mainly of elderly patients with a high frequency of cardiovascular risk factors. At follow-up of up to 5 years, there were 126 deaths from all causes (80 deaths from CVD). The lowest tertile of PON1 paraoxonase activity was associated with a higher risk of death in patients with NSTEMI, but not in patients with UA. CONCLUSION: PON1 paraoxonase activity has potential prognostic value in patients with NSTEMI.

Gluten-Free Diet Reduces Diet Quality and Increases Inflammatory Potential in Non-Celiac Healthy Women.

AIM: Gluten-free diets (GFDs) have gained popularity in the general population. Nonetheless, controlled studies are necessary before decisions can be made to promote GFDs. We aimed to evaluate the effects of gluten intake on body weight, body composition, and resting energy expenditure and observe the changes in nutrient intake caused by GFDs. METHODS: Twenty-three women were kept on a GFD for six weeks and received muffins with 20 g of gluten isolate (gluten period) or muffins without gluten (gluten-free period) in a crossover, single-blind, non-randomized trial. Gastrointestinal symptoms, food frequency questionnaires, body composition, and resting energy expenditure were assessed before the study (habitual or usual diet) and in the third and sixth weeks. Food intake was recorded daily for six weeks. RESULTS: Gastrointestinal symptoms, resting energy expenditure, and body weight and composition were similar during the gluten period and gluten-free period. When the diet of the gluten-free period was compared with the habitual diet, we found an increase in the intake of fat and sodium and a reduction in the intake of fiber and vitamins B1, B6, B12, and folate. The nutrient imbalance caused by a GFD led to an increase in the dietary inflammatory index, thus suggesting that this type of diet has high inflammatory potential. CONCLUSION: Gluten intake (20 g/day) did not alter body composition and resting energy expenditure in healthy women without caloric restriction in the diet for a short period (three weeks). However, a GFD led to changes in the composition of the diet, which worsened the quality of the diet and increased its inflammatory potential.

Melatonin administration attenuates acute stress by inducing sleep state in zebrafish (Danio rerio).

Melatonin plays a fundamental homeostatic role in basic biological functions, and an anti-stress role has been also proposed for this hormone. This study aimed to evaluate hormonal, enzymatic and behavioral parameters of zebrafish that received administration of melatonin and were submitted to acute stress. A total of 120 wild-type zebrafish were divided into five groups: naïve control (N), negative control group (Stress/C), positive control treated with diazepam (Stress/Diaz), treatment with melatonin at dose 1 (Stress/Melt. 1) and treatment with melatonin at dose 2 (Stress/Melt. 2). The exposure to treatments (diazepam or melatonin) was performed prior to the acute stress protocol, based on a chase by a fishing net during 5 min followed by exposure to the air for 1 min. The body cortisol levels were assessed, as well as oxidative stress (thiobarbituric acid reactive substances, reactive species of oxygen and antioxidant activity), and fish behavior (open field test). Melatonin was able to modulate acute stress effects on zebrafish by inhibiting cortisol increasing levels, reducing locomotor parameters, inducing a sleep state, reducing lipid peroxidation and stimulating antioxidant enzymatic activity.

Eating in the Amazon: Nutritional Status of the Riverine Populations and Possible Nudge Interventions.

The Amazon is the largest tropical forest in the world and a source of healthy food, such as fruits and fish. Surprisingly, the Amazonian riverine population present an increased prevalence (as high as 58%) of non-communicable diseases, such as hypertension and insulin resistance, even higher than that described for the urban population of the Amazon. Therefore, this work aimed to analyze the nutritional status and associated risk of the riverine population. Body mass index, waist circumference (WC), waist-to-hip ratio, and neck circumference (NC) were evaluated, and risk analysis was assayed. Furthermore, data about occupation and the prevalence of consumers of the different groups of food were analyzed. All anthropometric parameters revealed high proportions of individuals at risk, WC and NC being the factors that had more high-risk women and men, respectively. Our data confirmed the characteristic profile of the riverine communities with a high number of fish consumers, but also observed different patterns probably associated to a phenomenon of nutrition transition. Based on our data, some nudge interventions that take into account the principles of behavior analysis are discussed and proposed for these populations, aiming to improve the nutritional status and avoid the long-term consequences of the results showed by this work.

Prophylactic and therapeutic supplementation using fructo-oligosaccharide improves the intestinal homeostasis after mucositis induced by 5- fluorouracil.

The beneficial effects of prebiotic, such as fructo-oligosaccharides (FOS), in intestinal inflammation have been demonstrated in several studies. Herein, we evaluate whether joint treatment with FOS, both before and during mucositis, had additional beneficial effects and investigated the mechanisms underlying in the action of FOS on the intestinal barrier. BALB/c mice were randomly divided into five groups: CTR (without mucositis + saline solution), FOS (without mucositis + 6 % FOS), MUC (mucositis + saline solution), PT (mucositis + 6 % FOS supplementation before disease induction), and TT (mucositis + 6 % FOS supplementation before and during disease induction). Mucositis was induced by intraperitoneal injection (300 mg/kg) of 5-fluorouracil (5-FU). After 72 h, the animals were euthanized and intestinal permeability (IP), tight junction, bacterial translocation (BT), histology and morphometry, and immunoglobulin A secretory (sIgA), inflammatory infiltrate, and production of short-chain fatty acids (acetate, butyrate and propionate) were evaluated. The MUC group showed an increase in the IP, BT, and inflammatory infiltrate but a decrease in the tight junction expression and butyrate and propionate levels (P < 0.05). In the PT and TT groups, FOS supplementation maintained the IP, tight junction expression, and propionate concentration within physiologic levels, increased butyrate levels, and reduced BT and inflammatory infiltrate (P < 0.05). Total treatment with FOS (TT group) was more effective in maintaining histological score, morphometric parameters, and sIgA production. Thus, total treatment (prophylactic and therapeutic supplementation) with FOS was more effective than pretreatment alone, in reducing 5-FU-induced damage to the intestinal barrier.

The prognostic value of nitrotyrosine levels in coronary heart disease: long-term evaluation in the Acute Coronary Syndrome Registry Strategy (ERICO study).

INTRODUCTION: We aimed to analyze the association of nitrotyrosine (N-TYR) levels and long-term survival in an ongoing coronary heart disease (CHD) prospective cohort, the Acute Coronary Syndrome Registry Strategy (ERICO study). METHODS: N-TYR levels collected during acute and subacute phase from onset of acute coronary syndrome (ACS) symptoms (myocardial infarction and unstable angina) were evaluated in 342 patients. We calculated case-fatality rates (180-days, 1 year, 2 years and 4 years) and survival analyses up to 4 years using Kaplan-Meier curves and Cox regression with respective cumulative hazard ratios (95% confidence interval; 95%CI), according to N-TYR tertiles up to 4 years of follow-up. Models are presented as crude, age and sex-adjusted and further adjusted for lipids and other confounders. RESULTS: Overall, median level of N-TYR was 208.33 nmol/l (range: 3.09 to 1500 nmol/l), regardless ACS subtype. During follow-up of 4 years, we observed 44 (12.9%) deaths. Overall survival rate was 298 (87.1%) (Survival days: 1353, 95%CI: 1320-1387 days). N-TYR levels did not associate with mortality / survival rates up to 4 years. CONCLUSIONS: No relationship was found between N-TYR levels and mortality rates after ACS during 4-year follow-up in the ERICO study.

Antiobesity effects of anthocyanins on mitochondrial biogenesis, inflammation, and oxidative stress: A systematic review.

Studies have shown that anthocyanins attenuate obesity. In this review, we confirm these effects and explain the possible mechanisms underlying them. A systematic search was conducted in electronic databases using obesity as the main term along with anthocyanins and the main anthocyanidins, including articles in Portuguese, English, and Spanish without any restriction as to year. The review was carried out by peers following PRISMA recommendations: 1980 studies were identified, and 19 articles were analyzed. The studies varied in relation to time, pathways, cells used, and anthocyanin types. The positive effects were observed in 5' adenosine monophosphate-activated protein kinase pathways and mitochondrial biogenesis and in a reduction in inflammation and oxidative stress. Anthocyanins can improve the metabolic control involved in obesity by reducing lipogenesis, oxidative stress, and inflammation. This can boost the speed of lipolysis and thermogenesis, regulate satiety, and reduce body fat accumulation. In addition, anthocyanins have shown promising effects on controlling obesity compared with the standard of care.

Low serum levels of CCL2 are associated with worse prognosis in patients with Acute Coronary Syndrome: 2-year survival analysis.

Inflammation is very important in Acute Coronary Syndrome (ACS) as well as in cardiac remodeling after an acute myocardial infarction (MI). Our study examined the prognostic value of Chemokine (C-C motif) ligand 2 (CCL2) in patients with ACS in the ERICO (Strategy of Registry of Acute Coronary Syndrome) study. We evaluated serum samples from 803 patients. The prognostic value of CCL2 was evaluated at the 2-year follow-up, according to cutoff points established by the median. Kaplan-Meier curves and Cox regression were used for analysis of all-cause mortality, cardiovascular mortality, and a combined outcome of fatal myocardial infarction or new non-fatal MI. There were 115 deaths from all causes, 78 deaths due to cardiovascular causes and 67 events in combined outcomes. CCL2 levels below the median (≤100.9 pg/mL) were associated with increased risk of MI death or new non-fatal MI, even after model adjustment. Low serum levels of CCL2 shows a significant association with fatal or new non-fatal MI.

Myeloperoxidase activity and acute coronary syndrome survival: long-term evaluation in the ERICO study.

AIM: We aimed to analyze the influence of myeloperoxidase (MPO) activity on mortality in the Acute Coronary Syndrome Registry Strategy (ERICO) study. METHODS: MPO activity levels were evaluated in 342 patients. We performed survival analyses using Kaplan-Meier curves and Cox regression with respective hazard ratios, 95% CI, according to MPO tertiles distribution up to 7 years of follow-up. RESULTS: Higher MPO activity levels were seen in men, smokers, diabetics and those who were taking aspirin. MPO activity levels were neither significant in relation to mortality nor to survival rates up to seven years. CONCLUSION: We found no relationship between elevated levels of MPO activity post-acute coronary syndrome and mortality up to 7-years of follow-up in the ERICO study.

The polymorphism rs17782313 near MC4R gene is related with anthropometric changes in women submitted to bariatric surgery over 60 months.

OBJECTIVE: Evaluate whether the polymorphism rs17782313 near MC4R gene influences long-term outcomes after bariatric surgery. METHODS: The rs16782313 polymorphism was genotyped in 217 individuals undergoing bariatric surgery and analyzed in detail in 141 women. Data for comorbidities, BMI, excess weight loss (EWL), and body composition were obtained before and during 60 months after surgery. RESULTS: The risk allele was found in 65 (47%) of the 141 women. Pre-surgical body weight and BMI were higher in carriers of the rs17782313 polymorphism (CC + CT group) than in non-carriers (TT group) (p = 0.039 and 0.047, respectively). The number of women who acquired surgical success (EWL > 50%), was lower in CC + CT group compared to TT group (p = 0.015). The minimum BMI seen during the 60 months of follow-up was higher in CC + CT group compared to TT group (p = 0.028). The number of women who presented BMI < 30 kg/m2 (no longer classified as obesity) after 24 months of surgery was inferior in CC + CT group (6 out 35 patients - 17%) than in TT group (19 out 49 patients - 37%, p = 0.043). Moreover, the number of patients maintaining BMI > 35 kg/m2 were higher carriers (18 out 35 patients - 51%) compare to non-carriers (16 out 49 patients - 32%, p = 0.045). CONCLUSION: Women with extreme obesity carrying rs17782313 MC4R polymorphism present a higher pre-surgical BMI, are more unlikely to reach non-obesity BMI (<30 kg/m2) and tend to maintain a BMI > 35 kg/m2 that characterize treatment failure.

Conjugated linoleic acid prevents damage caused by intestinal mucositis induced by 5-fluorouracil in an experimental model.

BACKGROUND: Studies have showed the protective effects of conjugated linoleic acid (CLA) on intestinal epithelium, modulating host immune and inflammatory responses on intestinal diseases. OBJECTIVE: To evaluate the preventive effects of CLA on the intestinal mucositis induced by 5-FU in a murine model. METHODS: Sixty-four BALB/c mice were randomly divided into four groups: Control (CTL), fed a standard chow diet; CLAs, fed a diet supplemented with CLA; Mucositis (5-FU), fed a standard chow diet and underwent mucositis induction and CLAs 5-FU, fed a diet supplemented with CLA and underwent mucositis induction. Mucositis was induced by intraperitoneal injection of 300 mg/kg 5-FU. After 72 h, the animals were euthanized and intestinal permeability, bacterial translocation, inflammatory mediators, and intestinal histology were evaluated. RESULTS: Mice in the CLAs 5-FU group showed reduced weight loss compared to those in the 5-FU group (p < 0.005). Furthermore, the results also showed that the treatment with CLA reduced intestinal permeability, bacterial translocation, and biomarkers of inflammatory response besides minor damage to ZO-1 and occludin with maintenance of the integrity of the intestinal epithelium and a favorable balance between the inflammatory and regulatory cytokines. CONCLUSION: This study suggests that CLA reduced the adverse effects from 5-FU administration on the intestinal mucosa.