RAQUEL SUSANA MATOS DE MIRANDA TORRINHAS
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Gastroenterologia, Faculdade de Medicina
LIM/35 - Laboratório de Nutrição e Cirurgia Metabólica do Aparelho Digestivo, Hospital das Clínicas, Faculdade de Medicina
LIM/35 - Laboratório de Nutrição e Cirurgia Metabólica do Aparelho Digestivo, Hospital das Clínicas, Faculdade de Medicina
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- Effect of synbiotic in constipated adult women - A randomized, double-blind, placebo-controlled study of clinical response(2013) WAITZBERG, Dan L.; LOGULLO, Luciana C.; BITTENCOURT, Amanda E.; TORRINHAS, Raquel S.; SHIROMA, Glaucia M.; PAULINO, Natalia P.; TEIXEIRA-DA-SILVA, Maria L.Background & aims: Synbiotic intake may selectively change microbiota composition, restore microbial balance in the gut and improve gastrointestinal functions. We have assessed the clinical response of chronically constipated women to a commercially available synbiotic, combining fructooligosaccharides with Lactobacillus and Bifidobacterium strains (LACTOFOS (R)). Methods: Following 1 week of non-interventional clinical observation, 100 constipated adult women, diagnosed by ROME III criteria, were randomized to receive two daily doses (6 g) of synbiotic or maltodextrin (placebo group), for 30 days. Treatment response was evaluated by patient's daily record of evacuation (stool frequency, consistency and shape, according to Bristol scale), abdominal symptoms (abdominal pain, bloating and flatulence) and constipation intensity (Constipation Scoring System AGACHAN). Results: Patients treated with synbiotic had increased frequency of evacuation, as well as stool consistency and shape nearer normal parameters than the placebo group, with significant benefits starting during the second and third weeks, respectively (interaction group/time, P < 0.0001). There were no significant differences in abdominal symptoms, but AGACHAN score was better in the synbiotic than in the placebo group. Conclusions: Dietary supplementation with a synbiotic composed of fructooligosaccharides with Lactobacillus and Bifidobacterium improved evacuation parameters and constipation intensity of chronically constipated women, without influencing abdominal symptoms. NCT01286376 (C) 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
- Letter to the Editor(2011) TORRINHAS, Raquel; WAITZBERG, Dan
- Potential premalignant status of gastric portion excluded after Roux en-Y gastric bypass in obese women: A pilot study(2019) RAVACCI, Graziela Rosa; ISHIDA, Robson; TORRINHAS, Raquel Suzana; SALA, Priscila; MACHADO, Natasha Mendonca; FONSECA, Danielle Cristina; CANUTO, Gisele Andre Baptista; PINTO, Ernani; NASCIMENTO, Viviane; TAVARES, Marina Franco Maggi; SAKAI, Paulo; FAINTUCH, Joel; SANTO, Marco Aurelio; MOURA, Eduardo Guimaraes Hourneaux; ARTIGIANI NETO, Ricardo; LOGULLO, Angela Flavia; WAITZBERG, Dan LinetzkyWe evaluated whether the excluded stomach (ES) after Roux-en-Y gastric bypass (RYGB) can represent a premalignant environment. Twenty obese women were prospectively submitted to double-balloon enteroscopy (DBE) with gastric juice and biopsy collection, before and 3 months after RYGB. We then evaluated morphological and molecular changes by combining endoscopic and histopathological analyses with an integrated untargeted metabolomics and transcriptomics multiplatform. Preoperatively, 16 women already presented with gastric histopathological alterations and an increased pH (>= 4.0). These gastric abnormalities worsened after RYGB. A 90-fold increase in the concentration of bile acids was found in ES fluid, which also contained other metabolites commonly found in the intestinal environment, urine, and faeces. In addition, 135 genes were differentially expressed in ES tissue. Combined analysis of metabolic and gene expression data suggested that RYGB promoted activation of biological processes involved in local inflammation, bacteria overgrowth, and cell proliferation sustained by genes involved in carcinogenesis. Accumulated fluid in the ES appears to behave as a potential premalignant environment due to worsening inflammation and changing gene expression patterns that are favorable to the development of cancer. Considering that ES may remain for the rest of the patient's life, long-term ES monitoring is therefore recommended for patients undergoing RYGB.
- Is There an Advantage in Enriching Parenteral Lipid Emulsions Containing Fatty Acids From Fish Oil With Medium-Chain Triglycerides? A Study on Body Pool Concentrations of omega-3 Fatty Acids in Lewis Rats(2021) TESSER, Alweyd; TORRINHAS, Raquel S. M. M.; GARLA, Priscila C.; OLIVEIRA-FILHO, Ronaldo S.; APROBATO, Felipe G. G.; TAMANAHA, Erika M.; ANTUNES, Marcia S.; SAMPAIO, Geni R.; TORRES, Elizabeth; CALDER, Philip C.; WAITZBERG, Dan LinetzkyBackground The addition of medium-chain triglycerides (MCTs) into parenteral lipid emulsions rich in fatty acids from fish oil (FOLEs) has been shown to improve their clearance and extrahepatic uptake. We assessed whether this effect could favor the leukocyte uptake of omega-3 polyunsaturated fatty acids (PUFAs) for immunomodulatory purposes Methods Following 5-day adaptation in metabolic cages, 42 male Lewis rats fed with AIN-93M chow were killed (baseline control group [BC]) or submitted to central venous catheterization and distributed into (1) surgical control group without parenteral infusion (chow group), (2) test emulsion (MCT/LCT/FO) group with the parenteral infusion of a FOLE containing 40% MCT, and (3) control emulsion group (LCT/FO) with the parenteral infusion of an FOLE without MCT. The 2 FOLEs had similar omega-3 PUFA contents and omega-6/omega-3 PUFA ratios and were infused during 48 and 72 hours. Concentrations of omega-3 and omega-6 PUFAs in plasma, liver, and blood mononuclear and polymorphonuclear leukocytes were assessed by gas chromatography Results In both FOLE groups, leukocyte concentrations of omega-3 PUFAs peaked after 48 hours' infusion (vs BC). At this time point, plasma concentrations of omega-3 PUFAs were higher in MCT/LCT/FO group than in LCT/FO group and the opposite was found in the liver (P<.05), but no differences in PUFA concentrations were observed between these groups in leukocytes (P>.05) Conclusion The omega-3 PUFAs provided by FOLEs rich in MCT were less incorporated by liver and remained more available for extrahepatic cell delivery, but this did not result in a clear benefit in increasing their incorporation by peripheral leukocytes.
- Cell activation state influences the modulation of HLA-DR surface expression on human monocytes/macrophages by parenteral fish oil lipid emulsion(2011) TORRINHAS, R. S.; JACINTHO, T.; GOTO, H.; GIDLUND, M.; SALES, M. M.; OLIVEIRA, P. A.; WAITZBERG, D. L.Abnormal surface expression of HLA-DR by leukocytes is associated with a poor prognosis in critical care patients. Critical care patients often receive total parenteral nutrition with lipid emulsion (LE). In this study we evaluated the influence of fish oil LE (FO) on human monocyte/macrophage (M phi) expression of surface HLA-DR under distinct activation states. Mononuclear leukocytes from the peripheral blood of healthy volunteers (n=18) were cultured for 24 hours without LE (control) or with 3 different concentrations (0.1, 0.25, and 0.5%) of the follow LE: a) pure FO b) FO in association (1:1-v/v) with LE composed of 50% medium-chain trygliceride and 50% soybean oil (MCTSO), and c) pure MCTSO. The leukocytes were also submitted to different cell activation states, as determinate by INF-g addition time: no INF-gamma addition, 18 hours before, or at the time of LE addition. HLA-DR expression on MO surface was evaluated by flow cytometry using specific monoclonal antibodies. In relation to controls (for 0.1%, 0.25%, and 05%: 100) FO decreased the expression of HLA-DR when added alone in simultaneously-activated M., for 0.1%: 70 (59 +/- 73); for 0.25%: 51 (48 +/- 56); and for 05%: 52.5 (50 +/- 58)1 or in association with MCTSO [in simultaneously-activated MO, for 0.1%: 50.5 (47 +/- 61); for 25%: 49 (45 +/- 52); and for 0.5%: 51 (44 54) and in previously-activated Mf, for 1.0%: 63 (44 +/- 88); for 0.25%: 70 (41 +/- 88); and for 0.5%: 59.5 (39 +/- 79)1 in culture medium (Friedman p < 0.05). In relation to controls (for 0.1%, 0.25%, and 0.5%: 100), FO did not influence the expression of these molecules on non-activated M phi [for 0.1%: 87.5(75 +/- 93); for 0.25%: 111 (98 +/- 118); and for 0.5%: 101.5 (84 +/- 113)]. Results show that parenteral FO modulates the expression of HLA-DR on human MO surface accordingly to leukocyte activation state. Further clinical studies evaluating the ideal moment of fish oil LE infusion to modulate leukocyte functions may contribute to a better understanding of its immune modulatory properties.
- Understanding the gut microbiota in cancer cachexia(2023) ROCHA, Ilanna Marques; FONSECA, Danielle Cristina; TORRINHAS, Raquel Susana Matos; WAITZBERG, Dan LinetzkyPurpose of reviewCachexia is a complex, multifactorial syndrome primarily characterized by weight loss, muscle wasting, anorexia, and systemic inflammation. It is prevalent in cancer patients and is associated with a poor prognosis, including lower resistance to intervention toxicity, quality of life, and survival, compared to patients without the syndrome. The gut microbiota and its metabolites have been shown to influence host metabolism and immune response. Our article reviews the current evidence suggesting a role of gut microbiota in the development and progression of cachexia, while discussing the potential mechanisms involved. We also describe promising interventions targeting gut microbiota aiming to improve outcomes related to cachexia.Recent findingsDysbiosis, an imbalance in gut microbiota, has been associated with cancer cachexia through pathways involving muscle wasting, inflammation, and gut barrier dysfunction. Interventions targeting gut microbiota, such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have shown promising results in managing this syndrome in animal models. However, evidence in humans is currently limited.Mechanisms linking gut microbiota and cancer cachexia need to be further explored, and additional human research is necessary to evaluate the appropriate dosages, safety, and long-term outcomes of prebiotic and probiotic use in microbiota management for cancer cachexia.
- Human Leukocyte Death After a Preoperative Infusion of Medium/Long-Chain Triglyceride and Fish Oil Parenteral Emulsions: A Randomized Study in Gastrointestinal Cancer Patients(2012) CURY-BOAVENTURA, Maria Fernanda; TORRINHAS, Raquel Susana Matos de Miranda; GODOY, Andre Borella Pereira de; CURI, Rui; WAITZBERG, Dan LinetzkyBackground: Parenteral lipid emulsions (LEs) can influence leukocyte functions. The authors investigated the effect of 2 LEs on leukocyte death in surgical patients with gastrointestinal cancer. Material and Methods: Twenty-five patients from a randomized, double-blind clinical trial (ID: NCT01218841) were randomly included to evaluate leukocyte death after 3 days of preoperative infusion (0.2 g fat/kg/d) of an LE composed equally of medium/long-chain triglycerides and soybean oil (MCTs/LCTs) or pure fish oil (FO). Blood samples were collected before (t0) and after LE infusion (t1) and on the third postoperative day (t2). Results: After LE infusion (t1 vs t0), MCTs/LCTs did not influence cell death; FO slightly increased the proportion of necrotic lymphocytes (5%). At the postoperative period (t2 vs t0), MCTs/LCTs tripled the proportion of apoptotic lymphocytes; FO maintained the slightly increased proportion of necrotic lymphocytes (7%) and reduced the percentage of apoptotic lymphocytes by 74%. In the postoperative period, MCT/LCT emulsion increased the proportion of apoptotic neutrophils, and FO emulsion did not change any parameter of apoptosis in the neutrophil population. There were no differences in lymphocyte or neutrophil death when MCT/LCT and FO treatments were compared during either preoperative or postoperative periods. MCT/LCTs altered the expression of 12 of 108 genes related to cell death, with both pro- and antiapoptotic effects; FO modulated the expression of 7 genes, demonstrating an antiapoptotic effect. Conclusion: In patients with gastrointestinal cancer, preoperative MCT/LCT infusion was associated with postoperative lymphocyte and neutrophil apoptosis. FO has a protective effect on postoperative lymphocyte apoptosis. (JPEN J Parenter Enteral Nutr. 2012; 36: 677-684)
- High Prevalence of Energy and Nutrients Inadequacy among Brazilian Older Adults(2023) MAGALHAES, Natalia Vieira; WAITZBERG, Dan Linetzky; LOPES, Natalia Correia; VICEDOMINI, Ana Carolina Costa; PRUDENCIO, Ana Paula Aguiar; JACOB-FILHO, Wilson; BUSSE, Alexandre Leopold; FERDINANDO, Douglas; ALVES, Tatiana Pereira; PEREIRA, Rosa Maria Rodrigues; TORRINHAS, Raquel Susana; BELARMINO, GilianePoor nutrition increases the risk of diseases and adverse health outcomes in older adults. We evaluated the potential inadequacy of nutrient intake among older adults in Brazil and its association with body anthropometry and composition outcomes. Dietary intake was obtained from 295 community-living older adults (>60 years old), of both genders, using a seven-day food record. Nutrient inadequacy was further identified based on the Dietary Reference Intakes and European Guidelines. Skeletal muscle mass (SM), strength and performance, and the diagnosis of sarcopenia were assessed using reference methods. Nutritional inadequacy was high, with energy, dietary fiber, and six micronutrients exhibiting the greatest inadequacy levels (>80%). Energy intake was correlated with SM strength (p = 0.000) and performance (p = 0.001). Inadequate energy, fiber, and protein intakes influenced BMI, while inadequate intake of vitamin B6 directly affected the diagnosis of sarcopenia (p & LE; 0.005). Further research is required to investigate whether these inadequacies can be associated with other clinical health outcomes.
- Nutritional guidance, monitoring, and supplementation before and after bariatric surgery - Are we doing this correctly?(2021) SILVA, Mariane Marques da; WAITZBERG, Dan Linetzky; DIPPPOLITO, Regiane Macedo Silva; SALA, Priscila; BARCELOS, Samira; SANTO, Marco Aurelio; MARTINEZ, Ana Cristina; TORRINHAS, Raquel SusanaBackground and aims: minimizing nutritional depletions after a Roux-en-Y gastric bypass (RYGB) may improve clinical results in the treatment of obesity. We evaluated nutritional aspects of obese women undergoing RYGB at a reference university hospital with a department specialized in bariatric surgery. Method: based on the Dietary Reference Intakes developed by the Food and Nutrition Council, Institute of Medicine, and the guidelines issued by the American Society for Metabolic and Bariatric Surgery, we assessed the quantitative and qualitative adequacy of nutritional intake, supplementation, and biochemical monitoring of 20 women both before and 3 and 12 months after a RYGB. Data on nutritional intake was obtained by applying different food surveys, quantitatively interpreted by the Virtual Nutri Plus (R) software and using reference nutritional databases. Results: nutritional intake deficits were already found before the RYGB (p <= 0.05). These worsened postoperatively (p <= 0.05), a period also marked by a qualitatively poor diet. The nutritional supplementation prescribed did not fully achieve the reference recommendations, and was poorly complied with by patients. Furthermore, nutritional monitoring was not carried out in all patients, recommended biochemical markers were not screened, and vitamin D depletions occurred. Conclusion: our data suggest that institutions specialized in bariatric patient care may not be adequately adhering to well known guidelines, or applying efficient strategies to improve compliance.
- Gastrointestinal Transcriptomic Response of Metabolic Vitamin B12 Pathways in Roux-en-Y Gastric Bypass(2017) SALA, Priscila; BELARMINO, Giliane; TORRINHAS, Raquel S.; MACHADO, Natasha M.; FONSECA, Danielle C.; RAVACCI, Graziela R.; ISHIDA, Robson K.; GUARDA, Ismael F. M. S.; MOURA, Eduardo G. de; SAKAI, Paulo; SANTO, Marco A.; SILVA, Ismael D. C. G. da; PEREIRA, Claudia C. A.; LOGULLO, Angela F.; HEYMSFIELD, Steven; GIANNELLA-NETO, Daniel; WAITZBERG, Dan L.OBJECTIVES: Vitamin B12 (B12) deficiency after Roux-en-Y gastric bypass (RYGB) is highly prevalent and may contribute to postoperative complications. Decreased production of intrinsic factor owing to gastric fundus removal is thought to have a major role, but other components of B12 metabolism may also be affected. We evaluated changes in the expression levels of multiple B12 pathway-encoding genes in gastrointestinal (GI) tissues to evaluate the potential roles in contributing to post-RYGB B12 deficiency. METHODS: During double-balloon enteroscopy, serial GI biopsies were collected from 20 obese women (age, 46.9 +/- 6.2 years; body mass index, 46.5 +/- 5.3 kg/m(2)) with adult-onset type 2 diabetes (fasting plasma glucose >= 126 mg/dl; hemoglobin A1c >= 6.5%) before and, at the same site, 3 months after RYGB. Gene expression levels were assessed by the Affymetrix Human GeneChip 1.0 ST microarray. Findings were validated by real-time quantitative PCR (RT-qPCR). RESULTS: Gene expression levels with significant changes (P <= 0.05) included: transcobalamin I (TCN1) in remnant (-1.914-fold) and excluded (-1.985-fold) gastric regions; gastric intrinsic factor (GIF) in duodenum (-0.725-fold); and cubilin (CUBN) in duodenum (+0.982-fold), jejunum (+1.311-fold), and ileum (+0.685-fold). Validation by RT-qPCR confirmed (P <= 0.05) observed changes for TCN1 in the remnant gastric region (-0.132-fold) and CUBN in jejunum (+2.833-fold). CONCLUSIONS: RYGB affects multiple pathway-encoding genes that may be associated with postoperative B12 deficiency. Decreased TCN1 levels seem to be the main contributing factor. Increased CUBN levels suggest an adaptive genetic reprogramming of intestinal tissue aiming to compensate for impaired intestinal B12 delivery.