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1.
Gut ; 68(3): 522-532, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30301768

RESUMO

OBJECTIVE: Sustained inflammation originating from macrophages is a driving force of fibrosis progression and resolution. Monoacylglycerol lipase (MAGL) is the rate-limiting enzyme in the degradation of monoacylglycerols. It is a proinflammatory enzyme that metabolises 2-arachidonoylglycerol, an endocannabinoid receptor ligand, into arachidonic acid. Here, we investigated the impact of MAGL on inflammation and fibrosis during chronic liver injury. DESIGN: C57BL/6J mice and mice with global invalidation of MAGL (MAGL -/- ), or myeloid-specific deletion of either MAGL (MAGLMye-/-), ATG5 (ATGMye-/-) or CB2 (CB2Mye-/-), were used. Fibrosis was induced by repeated carbon tetrachloride (CCl4) injections or bile duct ligation (BDL). Studies were performed on peritoneal or bone marrow-derived macrophages and Kupffer cells. RESULTS: MAGL -/- or MAGLMye-/- mice exposed to CCl4 or subjected to BDL were more resistant to inflammation and fibrosis than wild-type counterparts. Therapeutic intervention with MJN110, an MAGL inhibitor, reduced hepatic macrophage number and inflammatory gene expression and slowed down fibrosis progression. MAGL inhibitors also accelerated fibrosis regression and increased Ly-6Clow macrophage number. Antifibrogenic effects exclusively relied on MAGL inhibition in macrophages, since MJN110 treatment of MAGLMye-/- BDL mice did not further decrease liver fibrosis. Cultured macrophages exposed to MJN110 or from MAGLMye-/- mice displayed reduced cytokine secretion. These effects were independent of the cannabinoid receptor 2, as they were preserved in CB2Mye-/- mice. They relied on macrophage autophagy, since anti-inflammatory and antifibrogenic effects of MJN110 were lost in ATG5Mye-/- BDL mice, and were associated with increased autophagic flux and autophagosome biosynthesis in macrophages when MAGL was pharmacologically or genetically inhibited. CONCLUSION: MAGL is an immunometabolic target in the liver. MAGL inhibitors may show promising antifibrogenic effects during chronic liver injury.


Assuntos
Anti-Inflamatórios/uso terapêutico , Cirrose Hepática Experimental/tratamento farmacológico , Fígado/enzimologia , Monoacilglicerol Lipases/antagonistas & inibidores , Animais , Anti-Inflamatórios/farmacologia , Autofagia/efeitos dos fármacos , Carbamatos/farmacologia , Carbamatos/uso terapêutico , Tetracloreto de Carbono , Contagem de Células , Células Cultivadas , Citocinas/metabolismo , Progressão da Doença , Avaliação Pré-Clínica de Medicamentos/métodos , Hidrolases/metabolismo , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/enzimologia , Cirrose Hepática Experimental/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Terapia de Alvo Molecular/métodos , Monoacilglicerol Lipases/fisiologia , Receptor CB2 de Canabinoide/metabolismo , Succinimidas/farmacologia , Succinimidas/uso terapêutico
2.
Am J Physiol Gastrointest Liver Physiol ; 317(5): G592-G601, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31460792

RESUMO

Bariatric surgery may induce protein malabsorption, although data are scarce. This study aims at evaluating dietary protein bioavailability after different bariatric surgeries in rats. Diet-induced obese Wistar rats were operated for vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB). The control group was composed of pair-fed, sham-operated rats (Sham). Two weeks after surgery, rats were fed a 15N protein meal. Protein bioavailability was assessed by determination of 15N recovery in the gastrointestinal tract and organs 6 h after the meal. Fractional protein synthesis rate (FSR) was assessed using a flooding dose of 13C valine. Weight loss was the highest in RYGB rats and the lowest in Sham rats. Surprisingly, RYGB (95.6 ± 0.7%) improved protein digestibility (P = 0.045) compared with Sham (93.5 ± 0.5%) and VSG (93.8 ± 0.6%). In contrast, 15N retained in the liver (P = 0.001) and plasma protein (P = 0.037) was lower than in Sham, with a similar trend in muscle (P = 0.052). FSR was little altered by bariatric surgery, except for a decrease in the kidney of RYGB (P = 0.02). The 15N distribution along the small intestinal tissue suggests that dietary nitrogen was considerably retained in the remodeled mucosa of RYGB compared with Sham. This study revealed that in contrast to VSG, RYGB slightly improved protein digestibility but altered peripheral protein bioavailability. This effect may be ascribed to a higher uptake of dietary amino acids by the remodeled intestine.NEW & NOTEWORTHY Using a sensitive 15N meal test, we found that gastric bypass slightly improved protein digestibility compared with sleeve gastrectomy or control but, in contrast, lowered protein retention in the liver and muscles. This paradox can be due to a higher uptake of dietary nitrogen by the intestinal mucosa that was hypertrophied. This study provides new insight on the digestive and metabolic fate of dietary protein in different models of bariatric surgery in rats.


Assuntos
Proteínas Alimentares/farmacocinética , Derivação Gástrica/métodos , Animais , Disponibilidade Biológica , Proteínas Alimentares/metabolismo , Digestão , Derivação Gástrica/efeitos adversos , Mucosa Intestinal/metabolismo , Rim/metabolismo , Fígado/metabolismo , Masculino , Músculo Esquelético/metabolismo , Nitrogênio/farmacocinética , Ratos , Ratos Wistar
3.
Int J Obes (Lond) ; 43(2): 428-431, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29453461

RESUMO

Some shifts in the gut microbiota composition and its metabolic fingerprints have been associated to Sleeve gastrectomy (SG) and Roux-en-Y Gastric Bypass (RYGB). So far, plasma bile acids have been associated with post-operative glucose improvement and weight loss, but nothing is known about their metabolism in the gut lumen. As bile acids are physiologically transformed by the microbiota into various species, the aim of this work was to study how SG and RYGB-associated dysbiosis impact the bioconversion of bile acids in the intestinal lumen. Comparing SHAM (n = 9) with our validated rat models of SG (n = 5) and RYGB (n = 6), we quantified luminal bile acids along the gut and found that the metabolic transformation of bile acids (deconjugation, dehydroxylation, and epimerization) is not different from the duodenum to the colon. However, in the cecum where the biotransformation mainly takes place, we observed deep alterations of the microbiota composition, which were specific of each type of surgery. In conclusion, despite specific dysbiosis after surgery, the bile acids metabolism in the gut lumen is highly preserved, suggesting that a resilience of the gut microbiota occurs after these procedures.


Assuntos
Ácidos e Sais Biliares/metabolismo , Gastrectomia , Derivação Gástrica , Microbioma Gastrointestinal/fisiologia , Animais , Ácidos e Sais Biliares/sangue , Obesidade Mórbida/metabolismo , Obesidade Mórbida/cirurgia , Ratos , Ratos Wistar
4.
Crit Care ; 22(1): 175, 2018 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-29980218

RESUMO

BACKGROUND: Bloodstream infections of abdominal origin are usually associated with poor prognosis. We assessed the clinical and microbiological characteristics of critically ill patients admitted to the intensive care unit (ICU) for postoperative intra-abdominal infection (PIAI) and analysed the influence of bacteraemia on their outcome. METHODS: All consecutive PIAI patients admitted to the ICU between 1999 and 2014 were prospectively analysed. Bacteraemic patients (at least one positive blood culture in the 24 h preceding/following surgery) were compared with non-bacteraemic patients. Demographic characteristics, underlying disease, severity scores at the time of reoperation, microbiological results, therapeutic management, outcome, and survival were recorded. Results are expressed as median (interquartile range (IQR)) or proportions. RESULTS: Overall, 343 patients (54% male, 62 (49-73) years old) with PIAI were analysed, including 64 (19%) bacteraemic patients. Immunosuppression and cancer were more frequent in bacteraemic patients (p < 0.001 in both cases). No difference between groups was observed for the characteristics of initial surgery. Time to reoperation, site, and cause of PIAI were similar in both groups. At the time of reoperation, Sequential Organ Failure Assessment (SOFA) score was higher in bacteraemic patients (8 (6-10) versus 7 (4-10); p < 0.05). A predominance of Gram-positive (34%) and Gram-negative (47%) bacteria were recovered from blood cultures (polymicrobial bacteraemia in 9 (14%) patients and bacteraemia involving multidrug-resistant organisms in 14 (22%) patients). In multivariate analysis, risk factors for bacteraemia were immunosuppression or cancer, high SOFA score, and E. coli in peritoneal samples. Bacteraemia did not impact the management (with similar results for the adequacy of antibiotic therapy, anti-infective agents used, de-escalation or duration of therapy in both groups). Neither hospital mortality nor morbidity criteria differed between groups. Risk factors for mortality in multivariate analysis were urgent initial surgery, high Simplified Acute Physiology Score (SAPS) II score and documented antifungal therapy, but not perioperative bacteraemia. CONCLUSIONS: In this ICU population, bacteraemia did not change the overall management of patients with PIAI. Our data suggest that bacteraemic patients do not require a specific management.


Assuntos
Bacteriemia/etiologia , Infecções Intra-Abdominais/complicações , Prognóstico , APACHE , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/mortalidade , Hemocultura/métodos , Distribuição de Qui-Quadrado , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão/métodos , Feminino , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Infecções Intra-Abdominais/mortalidade , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Complicações Pós-Operatórias/mortalidade , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Escore Fisiológico Agudo Simplificado
5.
Gastroenterology ; 150(2): 454-64.e9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26481855

RESUMO

BACKGROUND & AIMS: Bariatric procedures, such as Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG), are the most effective approaches to resolve type 2 diabetes in obese individuals. Alimentary glucose absorption and intestinal disposal of blood glucose have not been directly compared between individuals or animals that underwent RYGB vs VSG. We evaluated in rats and humans how the gut epithelium adapts after surgery and the consequences on alimentary glucose absorption and intestinal disposal of blood glucose. METHODS: Obese male rats underwent RYGB, VSG, or sham (control) operations. We collected intestine segments from all rats; we performed histologic analyses and measured levels of messenger RNAs encoding the sugar transporters SGLT1, GLUT1, GLUT2, GLUT3, GLUT4, and GLUT5. Glucose transport and consumption were assayed using ex vivo jejunal loops. Histologic analyses were also performed on Roux limb sections from patients who underwent RYGB 1-5 years after surgery. Roux limb glucose consumption was assayed after surgery by positron emission and computed tomography imaging. RESULTS: In rats and humans that underwent RYGB, the Roux limb became hyperplasic, with an increased number of incretin-producing cells compared with the corresponding jejunal segment of controls. Furthermore, expression of sugar transporters and hypoxia-related genes increased and the nonintestinal glucose transporter GLUT1 appeared at the basolateral membrane of enterocytes. Ingested and circulating glucose was trapped within the intestinal epithelial cells of rats and humans that underwent RYGB. By contrast, there was no hyperplasia of the intestine after VSG, but the intestinal absorption of alimentary glucose was reduced and density of endocrine cells secreting glucagon-like peptide-1 increased. CONCLUSIONS: The intestine adapts differently to RYGB vs VSG. RYGB increases intestinal glucose disposal and VSG delays glucose absorption; both contribute to observed improvements in glycemia.


Assuntos
Glicemia/metabolismo , Gastrectomia/métodos , Derivação Gástrica , Absorção Intestinal , Mucosa Intestinal/metabolismo , Jejuno/metabolismo , Obesidade/cirurgia , Adaptação Fisiológica , Adulto , Animais , Modelos Animais de Doenças , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/genética , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Humanos , Hiperplasia , Mucosa Intestinal/patologia , Jejuno/patologia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , RNA Mensageiro/metabolismo , Ratos , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X
6.
World J Surg ; 41(4): 1035-1039, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27896401

RESUMO

BACKGROUND: Our aim is to report our initial experience with a novel technique which addresses morbid obesity and gastro-esophageal reflux disease (GERD) simultaneously by combination of laparoscopic sleeve gastrectomy (LSG) and simplified laparoscopic Hill repair (sLHR). METHODS: Retrospective analysis of LSG+sLHR patients >5 months postoperatively includes demographics, GERD status, proton-pump inhibitor (PPI) use, body mass index (BMI), excess BMI loss (EBMIL), complications and GERD-Health Related Quality of Life (GERD-HRQL) questionnaire. LSG+sLHR surgical technique: posterior cruroplasty,  standard LSG, fixation of the esophagogastric junction to the median arcuate ligament. RESULTS: Fourteen patients underwent LSG+sLHR [12 women and 2 men, mean (range) age 47 years (27-57), BMI 41 kg/m2 (35-65)]. Five patients had previous gastric banding (GB). All had symptomatic GERD confirmed by gastroscopy and/or upper-gastrointestinal contrast study, two with chronic cough, 10 took PPI daily. Twelve had hiatus hernia and two patulous cardia at surgical exploration. Associated interventions were three GB removals and one cholecystectomy. Postoperative complication was one surgical site infection. Follow-up of all patients at median 12.5 months (5-17) is as follows: symptomatic GERD 3/14 patients, chronic cough 0/14, daily PPI use in 1/14, mean EBMIL 68% (17-120), satisfaction 93%, mean GERD-HRQL score 3,28/50 (0-15), with 4 patients 0/50, occasional bloatedness in 2 patients and dysphagia not reported. CONCLUSION: The novel technique which combines LSG with sLHR is feasible, safe and can be associated with GB removal. Preliminary results showed patient satisfaction, high remission rate of preexisting GERD, decrease in PPI use and unimpaired weight loss. Further evaluation is necessary in a controlled and staged manner to establish the technique's real effectiveness.


Assuntos
Gastrectomia/métodos , Refluxo Gastroesofágico/cirurgia , Laparoscopia , Obesidade Mórbida/cirurgia , Adulto , Uso de Medicamentos , Feminino , Refluxo Gastroesofágico/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Inibidores da Bomba de Prótons/uso terapêutico , Estudos Retrospectivos
7.
J Minim Invasive Gynecol ; 24(7): 1218-1226, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28802956

RESUMO

STUDY OBJECTIVE: To compare the accuracies of magnetic resonance imaging (MRI) and rectal endoscopic sonography (RES) in the prediction of the infiltration depth of colorectal endometriosis. DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: A university teaching hospital. PATIENTS: Forty patients with symptomatic deep infiltrating endometriosis (DIE) of the rectum who underwent colorectal resection were included. INTERVENTIONS: All patients underwent abdominopelvic MRI and RES preoperatively to assess the infiltration depth of colorectal endometriosis, and segmental resection of the rectosigmoid by laparoscopy was performed if RES showed bowel invasion. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive and negative likelihood ratios (LRs), and intermethod agreement were calculated for DIE muscularis and submucosal/mucosal infiltration confirmed by histopathological analysis. MEASUREMENTS AND MAIN RESULTS: For MRI detection of DIE muscularis infiltration, the sensitivity, specificity, PPV, NPV, and negative LR were 68%, 100%, 100%, 20%, and 0.32, respectively. For the MRI detection of DIE submucosal/mucosal involvement, the sensitivity, specificity, PPV, NPV, and positive and negative LRs were 47%, 81%, 69%, 63%, 2.49, and 0.65, respectively. The PPV of RES detection of DIE muscularis infiltration was 93%. For the RES detection of DIE submucosal/mucosal layers, the sensitivity, specificity, PPV, NPV, and positive and negative LRs were 79%, 48%, 58%, 71%, 1.51, and 0.44, respectively. CONCLUSION: In the current study, MRI is valuable for detecting endometriosis of the rectum but is less accurate in detecting submucosal/mucosal involvement than RES. Magnetic resonance imaging was not successful for preoperative determination of segmental resection versus a more conservative approach. When bowel involvement is detected by MRI, RES is not essential. When symptoms suggest DIE in patients without intestinal lesions detected by MRI, RES is necessary to exclude bowel invasion.


Assuntos
Doenças do Colo/diagnóstico , Endometriose/diagnóstico , Endossonografia/métodos , Imageamento por Ressonância Magnética , Doenças Retais/diagnóstico , Reto/diagnóstico por imagem , Adulto , Doenças do Colo/cirurgia , Endometriose/cirurgia , Feminino , Humanos , Laparoscopia/métodos , Pessoa de Meia-Idade , Doenças Peritoneais/diagnóstico , Doenças Peritoneais/cirurgia , Valor Preditivo dos Testes , Doenças Retais/cirurgia , Reto/patologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
8.
Obes Surg ; 34(3): 707-715, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38273145

RESUMO

BACKGROUND: Incidence of post-operative complications after sleeve gastrectomy (SG) is low. However, the early identification of these complications remains crucial. Here, we report the impact of routine laboratory monitoring for the early diagnosis of complications after SG. MATERIAL AND METHODS: From January 2018 to December 2019, all consecutive patients who underwent primary SG (n = 457) were included. This was a comparative study of patients undergoing primary SG. Patients were divided into two groups: one group with routine laboratory monitoring performed at postoperative day (POD) 1 and 3 (LAB group) and another group without routine laboratory monitoring (control group). The study's primary endpoint was the overall impact of routine laboratory monitoring. The secondary endpoints were evaluation of patients with complications. RESULTS: The population in the two groups were similar in term of demographic and intra-operative data. There was a statistical difference between the two groups in term of length of stay (5.7 days in the LAB group and 3.5 days in the control group (p < 0.001)). There were 19 complications (6.0%) in the LAB group and 5 complications in the control group (3.5%) (p = 0.25). A cut-off C-reactive protein level of 46.3 mg/l was found to be significant (p = 0.006). In the LAB group, 9 patients (2.9%) required readmission vs. three patients (2.0%) in the control group (p = 0.62). CONCLUSION: The interest of routine laboratory monitoring after SG seems limited. Routine laboratory monitoring alone is not associated with earlier diagnosis of complications. This routine monitoring is associated with an increase of stay in hospital.


Assuntos
Laparoscopia , Obesidade Mórbida , Humanos , Tempo de Internação , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Gastrectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento
9.
J Clin Med ; 12(9)2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37176705

RESUMO

Bariatric surgery (BS) is currently the most effective treatment for obesity, with long-lasting weight loss and improvement of related co-morbidities [...].

10.
Obes Surg ; 33(4): 1121-1132, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36729363

RESUMO

PURPOSE: Sleeve gastrectomy with transit bipartition (SG-TB) could be an attractive alternative to Roux-en-Y gastric bypass (RYGB) on weight loss and improvement of comorbidities in patients with obesity. However, there is little long-term data. Translational research on a rat model could allow long-term projection to assess efficacy and safety of SG-TB. The aim of this research was to evaluate the long-term efficacy and safety of SG-TB compared to RYGB and SHAM in rat model. MATERIALS AND METHODS: Ninety-four male obese Wistar rats were distributed into 3 groups: SG-TB (n = 34), RYGB (n = 32), and SHAM (control group, n = 28). The percentage of total weight loss (%TWL), coprocalorimetry, glucose and insulin tolerance test, insulin, GLP-1, PYY, and GIP before and after surgery were assessed. The animals were followed over 6 months (equivalent to 16 years in humans). RESULTS: At 6 months, %TWL was significantly greater(p = 0.025) in the SG-TB group compared to the RYGB group. There was no difference between the groups (p = 0.86) in malabsorption 15 and 120 days postoperatively. Glucose tolerance was significantly improved (p = 0.03) in the SG-TB and RYGB groups compared to the preoperative state. Insulin secretion, at 3 months, was significantly more important in the SG-TB group (p = 0.0003), compared to the RYGB and SHAM groups. GLP-1 secretion was significantly increased in the SG-TB and RYGB groups compared to the preoperative state (p = 0.001) but similar between SG-TB and RYGB animals (p = 0.72). CONCLUSION: In a rat model, at long term compared to RYGB, SG-TB provides greater and better-maintained weight loss and an increased insulin secretion without impairing nutritional status.


Assuntos
Derivação Gástrica , Obesidade Mórbida , Humanos , Masculino , Ratos , Animais , Obesidade Mórbida/cirurgia , Estado Nutricional , Ratos Wistar , Obesidade/cirurgia , Insulina , Peptídeo 1 Semelhante ao Glucagon , Gastrectomia , Glucose , Redução de Peso , Estudos Retrospectivos , Resultado do Tratamento
11.
J Clin Med ; 12(5)2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36902635

RESUMO

Sleeve gastrectomy (SG) often induces gastroesophageal reflux, with few and discordant long-term data on the risk of Barrett's esophagus (BE) in operated patients. The aim of this study was to analyze the impact of SG on esogastric mucosa in a rat model at 24 weeks postoperatively, which corresponds to approximately 18 years in humans. After 3 months of a high-fat diet, obese male Wistar rats were subjected to SG (n = 7) or sham surgery (n = 9). Esophageal and gastric bile acid (BA) concentrations were measured at sacrifice, at 24 weeks postoperatively. Esophageal and gastric tissues were analyzed by routine histology. The esophageal mucosa of the SG rats (n = 6) was not significantly different in comparison to that of the sham rats (n = 8), with no esophagitis or BE. However, there was more antral and fundic foveolar hyperplasia in the mucosa of the residual stomach 24 weeks after SG than in the sham group (p < 0.001). Luminal esogastric BA concentrations did not differ between the two groups. In our study, SG induced gastric foveolar hyperplasia but no esophageal lesions at 24 weeks postoperatively in obese rats. Therefore, long-term endoscopic esophageal follow-up that is recommended in humans after SG to detect BE may also be useful for detecting gastric lesions.

12.
Front Cell Infect Microbiol ; 13: 1023441, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36936775

RESUMO

Extensive intestinal resection leads to Short Bowel Syndrome (SBS), the main cause of chronic intestinal failure. Colon preservation is crucial for spontaneous adaptation, to improve absorption and reduce parenteral nutrition dependence. Fecal microbiota transplantation (FMT), a promising approach in pathologies with dysbiosis as the one observed in SBS patients, was assessed in SBS rats with jejuno-colonic anastomosis. The evolution of weight and food intake, the lenght of intestinal villi and crypts and the composition of fecal microbiota of Sham and SBS rats, transplanted or not with high fat diet rat microbiota, were analyzed. All SBS rats lost weight, increased their food intake and exhibited jejunal and colonic hyperplasia. Microbiota composition of SBS rats, transplanted or not, was largely enriched with Lactobacillaceae, and α- and ß-diversity were significantly different from Sham. The FMT altered microbiota composition and α- and ß-diversity in Sham but not SBS rats. FMT from high fat diet rats was successfully engrafted in Sham, but failed to take hold in SBS rats, probably because of the specific luminal environment in colon of SBS subjects favoring aero-tolerant over anaerobic bacteria. Finally, the level of food intake in SBS rats was positively correlated with their Lactobacillaceae abundance. Microbiota transfer must be optimized and adapted to this specific SBS environment.


Assuntos
Síndrome do Intestino Curto , Ratos , Animais , Síndrome do Intestino Curto/terapia , Síndrome do Intestino Curto/microbiologia , Síndrome do Intestino Curto/patologia , Roedores , Transplante de Microbiota Fecal , Mucosa Intestinal/patologia , Jejuno
13.
J Clin Med ; 11(17)2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-36078906

RESUMO

One anastomosis gastric bypass (OAGB) is associated with similar metabolic improvements and weight loss as Roux-en-Y gastric bypass (RYGB). However, this bariatric procedure is still controversial as it is suspected to result in undernutrition. Reducing the size of the biliopancreatic limb of OAGB could be essential to maintain positive outcomes while preventing side effects. The objective of this study was to compare and contrast outcomes of OAGB with two different biliopancreatic limb lengths to RYGB and Sham surgery in obese and non-obese rats. Lean and diet-induced obese Wistar rats were operated on RYGB, OAGB with a short (15 cm OAGB-15) or a long (35 cm OAGB-35) biliopancreatic limb or Sham surgery. Body weight and food intake were monitored over 30 weeks, and rats underwent oral glucose and insulin tolerance tests with a pancreatic and gut hormone secretion assay. Macronutrient absorption was determined by fecal analyses. Statistical analyses used non-parametric one-way or two-way ANOVA tests. Compared to Sham rats, RYGB, OAGB-15 and OAGB-35 rats displayed a significant reduced weight. Weight loss was greater after OAGB-35 than after OAGB-15 or Sham surgery because of transient malabsorption. All OAGB- and RYGB-operated rats displayed an improved pancreatic and gut hormone secretion in response to a meal compared to Sham rats, these effects were independent of limb length, rat weight, and maintained overtime. In conclusion, glucose homeostasis was similarly improved in obese and non-obese OAGB-15 and OAGB-35 rats suggesting that shortening the biliopancreatic limb can improve the metabolic parameters without a major influence on weight.

14.
Sci Rep ; 11(1): 5884, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33723332

RESUMO

The pathogenic role of staphylococci in hospital-acquired postoperative intra-abdominal infections (HAIs) has never been evaluated. In a tertiary care university hospital, we assessed the clinical characteristics and outcomes of patients admitted to the intensive care unit for HAIs according to the presence of staphylococci (S-HAI) or their absence (nS-HAI) in peritoneal cultures. Patients with S-HAIs were compared to nS-HAIs patients. Overall, 380 patients were analyzed, including 87 (23%) S-HAI patients [29 Staphylococcus aureus (Sa-HAIs) and 58 coagulase-negative staphylococci (CoNS-HAIs)]. The clinical characteristics did not differ between the S-HAI and nS-HAI patients. Adequacy of empirical anti-infective therapy was achieved less frequently in the staphylococci group (54 vs 72%, respectively, p < 0.01). The 90-day (primary endpoint) and one-year mortality rates did not differ between these groups. The S-HAI patients had decreased rates of postoperative complication (p < 0.05). The adjusted analysis of the clinical outcomes reported a decreased frequency of surgical complications in the staphylococci group (OR 0.43, 95% CI [0.20-0.93], p = 0.03). While the trends toward decreased morbidity criteria were observed in S-HAI patients, the clinical outcomes were not different between the CoNS-HAI and Sa-HAI patients. In summary, our data are not substantial enough to conclude that staphylococci exhibit no pathogenicity in HAIs.


Assuntos
Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Unidades de Terapia Intensiva , Infecções Intra-Abdominais/epidemiologia , Infecções Intra-Abdominais/microbiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/microbiologia , Staphylococcus/fisiologia , Adulto , Idoso , Coagulase/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Peritônio/microbiologia , Prognóstico , Resultado do Tratamento
15.
Nat Commun ; 12(1): 110, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397977

RESUMO

Glucagon-Like Peptide-1 (GLP-1) undergoes rapid inactivation by dipeptidyl peptidase-4 (DPP4) suggesting that target receptors may be activated by locally produced GLP-1. Here we describe GLP-1 positive cells in the rat and human stomach and found these cells co-expressing ghrelin or somatostatin and able to secrete active GLP-1 in the rats. In lean rats, a gastric load of glucose induces a rapid and parallel rise in GLP-1 levels in both the gastric and the portal veins. This rise in portal GLP-1 levels was abrogated in HFD obese rats but restored after vertical sleeve gastrectomy (VSG) surgery. Finally, obese rats and individuals operated on Roux-en-Y gastric bypass and SG display a new gastric mucosa phenotype with hyperplasia of the mucus neck cells concomitant with increased density of GLP-1 positive cells. This report brings to light the contribution of gastric GLP-1 expressing cells that undergo plasticity changes after bariatric surgeries, to circulating GLP-1 levels.


Assuntos
Cirurgia Bariátrica , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Peptídeo 1 Semelhante ao Glucagon/metabolismo , 1-Metil-3-Isobutilxantina/farmacologia , Adulto , Sequência de Aminoácidos , Animais , Dieta Hiperlipídica , Feminino , Peptídeo 1 Semelhante ao Glucagon/química , Glucose/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/patologia , Fenótipo , Ratos Wistar
16.
Eur J Trauma Emerg Surg ; 46(6): 1335-1340, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31143982

RESUMO

PURPOSE: In postoperative peritonitis, Gram stain examination (GSE) of peritoneal fluid has been proposed as a guide for the prescription of glycopeptides and antifungal therapy in empirical antibiotherapy. No data support this approach for Gram-positive cocci. We aimed to evaluate the performance of GSE in predicting the results of the culture of peritoneal fluid. METHODS: In this retrospective single-center study, concordance between GSE and culture of peritoneal fluid was assessed for different types of microorganisms. Factors associated with concordance of the two tests were evaluated in the subpopulation of Gram-positive cocci peritonitis. RESULTS: Among the 152 episodes, the GSE was negative in 57 cases. The negative predictive value and the positive predictive value were 41% and 87% for Gram-positive cocci (GPC), 31% and 86% for Gram-negative bacilli, and 78% and 94% for fungi. GSE is not a reliable guide for the choice of empirical antibiotherapy and cannot reliably rule out the presence of GPC at culture. If we aim to achieve a high rate of adequacy, the systematic use of glycopeptide in the empirical antibiotherapy may be considered. CONCLUSION: GSE shows poor performance to predict the results of culture of peritoneal fluid in postoperative peritonitis. Avoiding covering resistant GPC cannot be based on the result of GSE.


Assuntos
Antibacterianos/uso terapêutico , Violeta Genciana , Peritonite/tratamento farmacológico , Peritonite/microbiologia , Fenazinas , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/microbiologia , Antibioticoprofilaxia , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Paris , Reoperação , Estudos Retrospectivos
17.
Sci Rep ; 10(1): 7393, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32355175

RESUMO

Although bariatric surgery is proven to sustain weight loss in morbidly obese patients, long-term adverse effects have yet to be fully characterized. This study compared the long-term consequences of two common forms of bariatric surgery: one-anastomosis gastric bypass (OAGB) and Roux-en-Y Gastric Bypass (RYGB) in a preclinical rat model. We evaluated the influence of biliopancreatic limb (BPL) length, malabsorption, and bile acid (BA) reflux on esogastric mucosa. After 30 weeks of follow-up, Wistar rats operated on RYGB, OAGB with a short BPL (15 cm, OAGB-15), or a long BPL (35 cm, OAGB-35), and unoperated rats exhibit no cases of esogastric cancer, metaplasia, dysplasia, or Barrett's esophagus. Compared to RYGB, OAGB-35 rats presented higher rate of esophagitis, fundic gastritis and perianastomotic foveolar hyperplasia. OAGB-35 rats also revealed the greatest weight loss and malabsorption. On the contrary, BA concentrations were the highest in the residual gastric pouch of OAGB-15 rats. Yet, no association could be established between the esogastric lesions and malabsorption, weight loss, or gastric bile acid concentrations. In conclusion, RYGB results in a better long-term outcome than OAGB, as chronic signs of biliary reflux or reactional gastritis were reported post-OAGB even after reducing the BPL length in a preclinical rat model.


Assuntos
Refluxo Biliar , Mucosa Esofágica , Esofagite , Derivação Gástrica/efeitos adversos , Mucosa Gástrica , Modelos Biológicos , Obesidade Mórbida , Complicações Pós-Operatórias , Animais , Refluxo Biliar/etiologia , Refluxo Biliar/metabolismo , Refluxo Biliar/patologia , Refluxo Biliar/fisiopatologia , Doença Crônica , Mucosa Esofágica/metabolismo , Mucosa Esofágica/patologia , Mucosa Esofágica/fisiopatologia , Esofagite/etiologia , Esofagite/metabolismo , Esofagite/patologia , Esofagite/fisiopatologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Mucosa Gástrica/fisiopatologia , Hiperplasia/etiologia , Hiperplasia/metabolismo , Hiperplasia/patologia , Hiperplasia/fisiopatologia , Obesidade Mórbida/metabolismo , Obesidade Mórbida/patologia , Obesidade Mórbida/fisiopatologia , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/metabolismo , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/fisiopatologia , Ratos , Ratos Wistar
18.
Cell Rep ; 33(4): 108270, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33113371

RESUMO

The exact mechanisms underlying the metabolic effects of bariatric surgery remain unclear. Here, we demonstrate, using a combination of direct and indirect calorimetry, an increase in total resting metabolic rate (RMR) and specifically anaerobic RMR after Roux-en-Y gastric bypass (RYGB), but not sleeve gastrectomy (SG). We also show an RYGB-specific increase in splanchnic sympathetic nerve activity and "browning" of visceral mesenteric fat. Consequently, selective splanchnic denervation abolishes all beneficial metabolic outcomes of gastric bypass that involve changes in the endocannabinoid signaling within the small intestine. Furthermore, we demonstrate that administration of rimonabant, an endocannabinoid receptor-1 (CB1) inverse agonist, to obese mice mimics RYGB-specific effects on energy balance and splanchnic nerve activity. On the other hand, arachidonoylethanolamide (AEA), a CB1 agonist, attenuates the weight loss and metabolic signature of this procedure. These findings identify CB1 as a key player in energy regulation post-RYGB via a pathway involving the sympathetic nervous system.


Assuntos
Endocanabinoides/uso terapêutico , Derivação Gástrica/métodos , Sistema Nervoso Simpático/fisiologia , Animais , Endocanabinoides/farmacologia , Feminino , Humanos , Masculino , Camundongos
19.
Obes Surg ; 29(12): 3919-3927, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31388964

RESUMO

BACKGROUND: Few series are available on the results of repeat sleeve gastrectomy (re-SG) and Roux-en-Y gastric bypass (RYGB) performed to manage the failure of primary sleeve gastrectomy (SG). The objective of this study was to compare the short- and medium-term outcomes of re-SG and RYGB after SG. MATERIAL & METHODS: Between January 2010 and December 2017, patients undergoing re-SG (n = 61) and RYGB (n = 83) for failure of primary SG were included in this study. Revisional surgery was proposed for patients with insufficient excess weight loss (EWL ≤ 50%) or weight regain. The primary endpoint was the comparison of weight loss in the re-SG group and the RYGB group at the 1-year follow-up. The secondary endpoints were overall mortality and morbidity, specific morbidity, length of stay, weight loss, and correction of comorbidities. RESULTS: The mean interval between SG and re-SG was 41.5 vs. 43.2 months between SG and RYGB (p = 0.32). The mean operative time was 103 min (re-SG group) vs. 129.4 min (RYGB group). One death (1.7%; re-SG group) and 25 complications (17.4%; 9 in the re-SG group, 16 in the RYGB group) were observed. At the 1 year, mean body mass index was 31.6 in the re-SG group and 32.5 in the RYGB group (p = 0.61) and excess weight loss was 69.5 vs. 61.2, respectively (p = 0.05). CONCLUSION: Re-SG and RYGB as revisional surgery for SG are feasible with acceptable outcomes and similar results on weight loss on the first postoperative year.


Assuntos
Gastrectomia/métodos , Derivação Gástrica/métodos , Obesidade Mórbida/cirurgia , Reoperação/métodos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de Tratamento , Redução de Peso
20.
Nutr Rev ; 77(3): 129-143, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30517714

RESUMO

The plasticity of a material corresponds to its capacity to change its feature under the effect of an external action. Intestinal plasticity could be defined as the ability of the intestine to modify its size or thickness and intestinal cells to modulate their absorption and secretion functions in response to external or internal cues/signals. This review will focus on intestinal adaptation mechanisms in response to diet and nutritional status. These physiological mechanisms allow a fine and rapid adaptation of the gut to promote absorption of ingested food, but they can also lead to obesity in response to overnutrition. This plasticity could thus become a therapeutic target to treat not only undernutrition but also obesity. How the intestine adapts in response to 2 types of surgical remodeling of the digestive tract-extensive bowel resection leading to intestinal failure and surgical treatment of pathological obesity (ie, bariatric surgeries)-will also be reviewed.


Assuntos
Adaptação Fisiológica , Dieta , Procedimentos Cirúrgicos do Sistema Digestório , Intestinos/fisiologia , Estado Nutricional , Animais , Feminino , Humanos , Absorção Intestinal , Intestinos/cirurgia , Masculino
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