Viabilidad de la sutura gástrica con adhesivos sintéticos de última generación : estudio experimental en ratas /

Premi Extraordinari de Doctorat concedit pels programes de doctorat de la UAB per curs acadèmic 2017-2018Introducción: La eficacia clínica y la seguridad de los adhesivos biológicos y sintéticos en las suturas digestivas ya han sido evaluadas. Sin embargo, poco se sabe acerca de su papel en las suturas y anastomosis gástricas. Por otra parte, la utilización de nuevos tipos de adhesivos sintéticos a partir del n-butil-cianoacrilato no se han evaluado todavía. Materiales y Métodos: Se realizó una gastrotomía de un centímetro en 24 ratas macho tipo Wistar, que se dividieron en función del tipo de método de sutura empleado: Sutura manual de 5/0 de seda discontínua versus sutura con adhesivo sintético tipo Histoacryl ™ flexible (n-butil-cianocrilato con "softener") o tipo Histoacryl ™ Doble Componente (n-butil-cianoacrilato con "softener" y "hardener"). El objetivo de la valoración principal fue identificar las diferencias en la incidencia de fugas anastomóticas, la formación de adherencias y hallazgos microscópicos durante el proceso de cicatrización. Durante 8 semanas de seguimiento se estudiaron aspectos clínicos e histopatológicos, así como también perfiles hematológicos, iónicos y marcadores inflamatorios. Resultados: No se observaron diferencias significativas entre los grupos cuando se compararon los aspectos clínicos, analíticos o histopatológicos evaluados. Sólo se evidenció una mayor tasa de incidencia de adherencias en el grupo Histoacryl doble componente en comparación con el grupo de sutura manual (p = 0,04). Nuestros resultados indican que ambos tipos de n-butil-cianoacrilato son materiales fiables para el cierre gástrico sin efectos secundarios significativos ni locales ni sistémicos.Background: Clinical effectiveness and safety of biological and synthetic adhesives in digestive closures have been evaluated. However, little is known about their role in gastric and anastomotic closures. Moreover, usefulness of novel types of synthetic adhesives as n-butyl-cyanoacrylate has not been assessed yet. Materials and Methods: One centimeter long gastrotomy was performed in 24 male Wistar rats which were divided depending on the type of closure method employed: manual USP 5/0 silk interrupted suture versus suture-less closure with Histoacryl™ flexible (n-butyl-cyanoacrylate with softener ) or Histoacryl™ Double Component (n-butyl-cyanoacrylate with softener and hardener ). The primary endpoint was to identify differences in the incidence of anastomotic leaks, adhesion formation and microscopic findings during the cicatrization process. During an 8-week follow-up clinical and histopathological aspects as well as hematologic, ionic and inflammatory markers were studied. Results: No differences among groups where found in any of the clinical, analytical or histopathological issues assessed except for a higher incidence rate of adhesions in the Histoacryl Double Component group when compared with hand-sewn suture group (p = 0.04). Our results indicate that both types of n-butyl-cyanoacrylate are reliable materials for gastric closure without significant neither local nor systemic side effects

Differential association between S100A4 levels and insulin resistance in prepubertal children and adult subjects with clinically severe obesity

Objectives: S100A4 has been recently identified as an adipokine associated with insulin resistance (IR) in adult subjects with obesity. However, no data about its levels in children with obesity and only a few approaches regarding its potential mechanism of action have been reported. To obtain a deeper understanding of the role of S100A4 in obesity, (a) S100A4 levels were measured in prepubertal children and adult subjects with and without obesity and studied the relationship with IR and (b) the effects of S100A4 in cultured human adipocytes and vascular smooth muscle cells (VSMCs) were determined. Methods: Sixty-five children (50 with obesity, age 9.0 ±1.1 years and 15 normal weight, age 8.4 ±0.8 years) and fifty-nine adults (43 with severe obesity, age 46 ±11 years and 16 normal weight, age 45 ±9 years) were included. Blood from children and adults and adipose tissue samples from adults were obtained and analysed. Human adipocytes and VSMC were incubated with S100A4 to evaluate their response to this adipokine. Results: Circulating S100A4 levels were increased in both children (P = .002) and adults (P < .001) with obesity compared with their normal-weight controls. In subjects with obesity, S100A4 levels were associated with homeostatic model assessment-insulin resistance (HOMA-IR) in adults (βstd = .42, P = .008) but not in children (βstd = .12, P = .356). Human adipocytes were not sensitive to S100A4, while incubation with this adipokine significantly reduced inflammatory markers in VSMC. Conclusions: Our human data demonstrate that higher S100A4 levels are a marker of IR in adults with obesity but not in prepubertal children. Furthermore, the in vitro results suggest that S100A4 might exert an anti-inflammatory effect. Further studies will be necessary to determine whether S100A4 can be a therapeutic target for obesity

Differential association between S100A4 levels and insulin resistance in prepubertal children and adult subjects with clinically severe obesity

Objectives: S100A4 has been recently identified as an adipokine associated with insulin resistance (IR) in adult subjects with obesity. However, no data about its levels in children with obesity and only a few approaches regarding its potential mechanism of action have been reported. To obtain a deeper understanding of the role of S100A4 in obesity, (a) S100A4 levels were measured in prepubertal children and adult subjects with and without obesity and studied the relationship with IR and (b) the effects of S100A4 in cultured human adipocytes and vascular smooth muscle cells (VSMCs) were determined. Methods: Sixty-five children (50 with obesity, age 9.0 ±1.1 years and 15 normal weight, age 8.4 ±0.8 years) and fifty-nine adults (43 with severe obesity, age 46 ±11 years and 16 normal weight, age 45 ±9 years) were included. Blood from children and adults and adipose tissue samples from adults were obtained and analysed. Human adipocytes and VSMC were incubated with S100A4 to evaluate their response to this adipokine. Results: Circulating S100A4 levels were increased in both children (P =.002) and adults (P <.001) with obesity compared with their normal-weight controls. In subjects with obesity, S100A4 levels were associated with homeostatic model assessment-insulin resistance (HOMA-IR) in adults (βstd =.42, P =.008) but not in children (βstd =.12, P =.356). Human adipocytes were not sensitive to S100A4, while incubation with this adipokine significantly reduced inflammatory markers in VSMC. Conclusions: Our human data demonstrate that higher S100A4 levels are a marker of IR in adults with obesity but not in prepubertal children. Furthermore, the in vitro results suggest that S100A4 might exert an anti-inflammatory effect. Further studies will be necessary to determine whether S100A4 can be a therapeutic target for obesity

A role for Oncostatin M in the impairment of glucose homeostasis in obesity

CONTEXT: Oncostatin M (OSM) plays a key role in inflammation, but its regulation and function during obesity is not fully understood. OBJECTIVE: The aim of this study was to evaluate the relationship of OSM with the inflammatory state that leads to impaired glucose homeostasis in obesity. We also assessed whether OSM immunoneutralization could revert metabolic disturbances caused by a high-fat diet (HFD) in mice. DESIGN: 28 patients with severe obesity were included and stratified into two groups: (1) glucose levels 100 mg/dL. White adipose tissue was obtained to examine OSM gene expression. Human adipocytes were used to evaluate the effect of OSM in the inflammatory response, and HFD-fed C57BL/6J mice were injected with anti-OSM antibody to evaluate its effects. RESULTS: OSM expression was elevated in subcutaneous and visceral fat from patients with obesity and hyperglycemia, and correlated with Glut4 mRNA levels, serum insulin, homeostatic model assessment of insulin resistance, and inflammatory markers. OSM inhibited adipogenesis and induced inflammation in human adipocytes. Finally, OSM receptor knockout mice had increased Glut4 mRNA levels in adipose tissue, and OSM immunoneutralization resulted in a reduction of glucose levels and Ccl2 expression in adipose tissue from HFD-fed mice. CONCLUSIONS: OSM contributes to the inflammatory state during obesity and may be involved in the development of insulin resistance

Viabilidad de la sutura gastrica con adhesivos sinteticos de ultima generacion. Estudio experimental en ratas

Introducción: La eficacia clínica y la seguridad de los adhesivos biológicos y sintéticos en las suturas digestivas ya han sido evaluadas. Sin embargo, poco se sabe acerca de su papel en las suturas y anastomosis gástricas. Por otra parte, la utilización de nuevos tipos de adhesivos sintéticos a partir del n-butil-cianoacrilato no se han evaluado todavía. Materiales y Métodos: Se realizó una gastrotomía de un centímetro en 24 ratas macho tipo Wistar, que se dividieron en función del tipo de método de sutura empleado: Sutura manual de 5/0 de seda discontínua versus sutura con adhesivo sintético tipo Histoacryl ™ flexible (n-butil-cianocrilato con “softener”) o tipo Histoacryl ™ Doble Componente (n-butil-cianoacrilato con “softener” y “hardener”). El objetivo de la valoración principal fue identificar las diferencias en la incidencia de fugas anastomóticas, la formación de adherencias y hallazgos microscópicos durante el proceso de cicatrización. Durante 8 semanas de seguimiento se estudiaron aspectos clínicos e histopatológicos, así como también perfiles hematológicos, iónicos y marcadores inflamatorios. Resultados: No se observaron diferencias significativas entre los grupos cuando se compararon los aspectos clínicos, analíticos o histopatológicos evaluados. Sólo se evidenció una mayor tasa de incidencia de adherencias en el grupo Histoacryl doble componente en comparación con el grupo de sutura manual (p = 0,04). Nuestros resultados indican que ambos tipos de n-butil-cianoacrilato son materiales fiables para el cierre gástrico sin efectos secundarios significativos ni locales ni sistémicos.Background: Clinical effectiveness and safety of biological and synthetic adhesives in digestive closures have been evaluated. However, little is known about their role in gastric and anastomotic closures. Moreover, usefulness of novel types of synthetic adhesives as n-butyl-cyanoacrylate has not been assessed yet. Materials and Methods: One centimeter long gastrotomy was performed in 24 male Wistar rats which were divided depending on the type of closure method employed: manual USP 5/0 silk interrupted suture versus suture-less closure with Histoacryl™ flexible (n-butyl-cyanoacrylate with softener ) or Histoacryl™ Double Component (n-butyl-cyanoacrylate with softener and hardener ). The primary endpoint was to identify differences in the incidence of anastomotic leaks, adhesion formation and microscopic findings during the cicatrization process. During an 8-week follow-up clinical and histopathological aspects as well as hematologic, ionic and inflammatory markers were studied. Results: No differences among groups where found in any of the clinical, analytical or histopathological issues assessed except for a higher incidence rate of adhesions in the Histoacryl Double Component group when compared with hand-sewn suture group (p = 0.04). Our results indicate that both types of n-butyl-cyanoacrylate are reliable materials for gastric closure without significant neither local nor systemic side effects

Use of infrared thermography to estimate brown fat activation after a cooling protocol in patients with severe obesity that underwent bariatric surgery

Background: In contrast to the energy-storing role of white adipose tissue (WAT), brown adipose tissue (BAT) acts as the main site of non-shivering thermogenesis in mammals and has been reported to play a role in protection against obesity and associated metabolic alterations in rodents. Infrared thermography (IRT) has been proposed as a novel non-invasive, safe, and quick method to estimate BAT thermogenic activation in humans. The aim of this study is to determine whether the IRT could be a potential new tool to estimate BAT thermogenic activation in patients with severe obesity in response to bariatric surgery. Methods: Supraclavicular BAT thermogenic activation was evaluated using IRT in a cohort of 31 patients (50 ± 10 years old, BMI = 44.5 ± 7.8; 15 undergoing laparoscopy sleeve gastrectomy and 16 Roux-en-Y gastric bypass) at baseline and 6 months after a bariatric surgery. Clinical parameters were determined at these same time points. Results: Supraclavicular BAT-related activity was detected in our patients by IRT after a cooling stimulus. The BAT thermogenic activation was higher at 6 months after laparoscopy sleeve gastrectomy (0.06 ± 0.1 vs 0.32 ± 0.1), while patients undergoing to a roux-en-Y gastric bypass did not change their thermogenic response using the same cooling stimulus (0.09 ± 0.1 vs 0.08 ± 0.1). Conclusions: Our study postulates the IRT as a potential tool to evaluate BAT thermogenic activation in patients with obesity before and after a bariatric surgery. Further studies are needed to evaluate differences between LSG technique and RYGB on BAT activation. Keywords: Brown adipose tissue; Infrared thermography; Metabolic surgery; Obesity

Lipidome Profiling in Childhood Obesity Compared to Adults: A Pilot Study.

The objective is to assess the circulating lipidome of children with obesity before and after lifestyle intervention and to compare the data to the circulating lipidome of adults with obesity before and after bariatric surgery. Ten pediatric (PE) and thirty adult (AD) patients with obesity were prospectively recruited at a referral single center. The PE cohort received lifestyle recommendations. The AD cohort underwent bariatric surgery. Clinical parameters and lipidome were analyzed in serum before and after six months of metabolic intervention. The abundance of phosphatidylinositols in the PE cohort and phosphatidylcholines in the AD significantly increased, while O-phosphatidylserines in the PE cohort and diacyl/triacylglycerols in the AD decreased. Fifteen lipid species were coincident in both groups after lifestyle intervention and bariatric surgery. Five species of phosphatidylinositols, sphingomyelins, and cholesteryl esters were upregulated. Eight species of diacylglycerols, glycerophosphoglycerols, glycerophosphoethanolamines, and phosphatidylcholines were downregulated. Most matching species were regulated in the same direction except for two phosphatidylinositols: PI(O-36:2) and PI(O-34:0). A specific set of lipid species regulated after bariatric surgery in adult individuals was also modulated in children undergoing lifestyle intervention, suggesting they may constitute a core circulating lipid profile signature indicative of early development of obesity and improvement after clinical interventions regardless of individual age

Interleukin-16 is increased in obesity and alters adipogenesis and inflammation in vitro

IntroductionObesity is a chronic condition associated with low-grade inflammation mainly due to immune cell infiltration of white adipose tissue (WAT). WAT is distributed into two main depots: subcutaneous WAT (sWAT) and visceral WAT (vWAT), each with different biochemical features and metabolic roles. Proinflammatory cytokines including interleukin (IL)-16 are secreted by both adipocytes and infiltrated immune cells to upregulate inflammation. IL-16 has been widely studied in the peripheral proinflammatory immune response; however, little is known about its role in adipocytes in the context of obesity.Aim &amp; MethodsWe aimed to study the levels of IL-16 in WAT derived from sWAT and vWAT depots of humans with obesity and the role of this cytokine in palmitate-exposed 3T3-L1 adipocytes.ResultsThe results demonstrated that IL-16 expression was higher in vWAT compared with sWAT in individuals with obesity. In addition, IL-16 serum levels were higher in patients with obesity compared with normal-weight individuals, increased at 6 months after bariatric surgery, and at 12 months after surgery decreased to levels similar to before the intervention. Our in vitro models showed that IL-16 could modulate markers of adipogenesis (Pref1), lipid metabolism (Plin1, Cd36, and Glut4), fibrosis (Hif1a, Col4a, Col6a, and Vegf), and inflammatory signaling (IL6) during adipogenesis and in mature adipocytes. In addition, lipid accumulation and glycerol release assays suggested lipolysis alteration.DiscussionOur results suggest a potential role of IL-16 in adipogenesis, lipid and glucose homeostasis, fibrosis, and inflammation in an obesity context

White adipose tissue-infiltrated CD11b+ myeloid cells are a source of S100A4, a new potential marker of hepatic damage

Context The endocrine and immunological properties of subcutaneous vs. visceral adipose tissue (sWAT and vWAT, respectively) have turned a milestone in the study of metabolic diseases. The cytokine S100A4 has been reported to be elevated in obesity and to have a role in adipose tissue dysfunction. However, the cellular source in adipose tissue and its potential role in hepatic damage in obesity has not been elucidated. Objective We aim to study the regulation of S100A4 in immune cells present in sWAT and vWAT, as well as its potential role as a circulating marker of hepatic inflammation and steatosis. Design A cohort of 60 patients with obesity and distinct metabolic status was analyzed. CD11b+ myeloid cells and T cells were isolated from sWAT and vWAT by magnetic-activating cell sorting, and RNA was obtained. S100A4 gene expression was measured, and correlation analysis with clinical data was performed. Liver biopsies were obtained from 20 patients, and S100A4 circulating levels were measured to check the link with hepatic inflammation and steatosis. Results S100A4 gene expression was strongly upregulated in sWAT- vs. vWAT-infiltrated CD11b+ cells, but this modulation was not observed in T resident cells. S100A4 mRNA levels from sWAT (and not from vWAT) CD11b+ cells positively correlated with glycemia, triglycerides and TNF-α gene expression. Finally, circulating S100A4 directly correlated with liver steatosis and hepatic inflammatory markers. Conclusion Our data suggest that sWAT-infiltrated CD11b+ cells could be a major source of S100A4 in obesity. Moreover, our correlations identify circulating S100A4 as a potential novel biomarker of hepatic damage and steatosis