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.
- 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.
- Partial Replacement of omega-6 Fatty Acids With Medium-Chain Triglycerides, but Not Olive Oil, Improves Colon Cytokine Response and Damage in Experimental Colitis(2012) BERTEVELLO, Pedro L.; NARDI, Leticia De; TORRINHAS, Raquel S.; LOGULLO, Angela F.; WAITZBERG, Dan L.Background: Soybean oil is rich in omega-6 fatty acids, which are associated with higher incidence and more severe cases of inflammatory bowel diseases. The authors evaluated whether partial replacement of soybean oil by medium-chain triglycerides (MCTs) or olive oil influenced the incidence and severity of experimental ulcerative colitis by using different parenteral lipid emulsions (LEs). Methods: Wistar rats (n = 40) were randomized to receive parenteral infusion of the following LE: 100% soybean oil (SO), 50% MCT mixed with 50% soybean oil (MCT/SO), 80% olive oil mixed with 20% soybean oil (OO/SO), or saline (CC). After 72 hours of infusion, acetic acid experimental colitis was induced. After 24 hours, colon histology and cytokine expression were analyzed. Results: SO was not significantly associated with overall tissue damage. MCT/SO was not associated with necrosis (P < .005), whereas OO/SO had higher frequencies of ulcer and necrosis (P < .005). SO was associated with increased expression of interferon-gamma (P = .005) and OO/SO with increased interleukin (IL)-6 and decreased tumor necrosis factor-alpha expression (P < .05). MCT/SO appeared to decrease IL-1 (P < .05) and increase IL-4 (P < .001) expression. Conclusions: Parenteral SO with high concentration of omega-6 fatty acids was not associated with greater tissue damage in experimental colitis. SO partial replacement with MCT/SO decreased the frequency of histological necrosis and favorably modulated cytokine expression in the colon; however, replacement with OO/SO had unfavorable effects. (JPEN J Parenter Enteral Nutr. 2012; 36: 442-448)
- Body adiposity index performance in estimating body fat in a sample of severely obese Brazilian patients(2015) BELARMINO, Giliane; HORIE, Lilian Mika; SALA, Priscila Campos; TORRINHAS, Raquel S.; HEYMSFIELD, Steven B.; WAITZBERG, Dan L.Background/objectives: The body adiposity index (BAI) estimates the amount of body fat (BF) in humans. In Mexican-American and African-American populations, BAI has performed better than body mass index (BMI). The aim of this study was to evaluate the performance of BAI in estimating percentage (BF%) in severely obese Brazilian patients, with air displacement plethysmography (ADP) used as the reference method. Subjects/methods: Estimation of BF% by ADP, anthropometric measurements (height, abdominal and hip circumferences, body weight, and BMI) and BAI calculation were performed in 72 obese subjects (BMI >= 30 kg/m(2)) aged 30-55 years. Results: The mean BF% estimates +/- standard deviation were 52.1 +/- 5.7 % for ADP and 47.7 +/- 7.4 % for BAI, with a positive Pearson correlation (r(p) = 0.66) and a positive Lin's concordance correlation (r(c) = 0.479) observed between these methods. The 95 % limits of individual agreement between BAI and ADP ranged from -5.769 % to 16.036 %, with BAI exhibiting an average positive bias of 5.13 % compared to the reference method. For each studied variable, BAI exhibited a systematic bias, as evidenced by a tendency for low BF% values to be overestimated. Conclusion: For Brazilian patients with severe obesity, BAI does not provide an accurate estimate of BF%.
- Infusion time for fish oil-containing parenteral emulsions in surgery: A study on omega-3 fatty acid dynamics in rats(2021) ANTUNES, Marcia S.; WAITZBERG, Dan L.; TESSER, Alweyd; GUTIERRES, Felipe A.; TAMANAHA, Erika M.; OLIVEIRA, Ronaldo; SAMPAIO, Geni; TORRES, Elizabeth A.; GARLA, Priscilla C.; CALDER, Phillip C.; TORRINHAS, Raquel S.Objectives: The aim of this study was to contribute to the design of specialized parenteral nutrition protocols in surgery by evaluating the dynamics of polyunsaturated fatty acid (PUFA) concentrations in different body pools after the infusion of fish oil-containing lipid emulsion (FOLE) in rats that had undergone surgical central venous catheterization (CVC). Methods: After 5-d adaptation in metabolic cages, 78 male Lewis rats (300-450 g) fed a standard diet were sacrificed (baseline control) or had only CVC (surgical control) or also received a 72-h infusion of a parenteral lipid emulsion with or without fish oil. The catheterized animals were sacrificed 0 (T0), 2 (T2), 6 (T6), and 12 h (T12) after the infusion ended. Gas chromatography was used to determine the concentrations of eicosapentaenoic (EPA), docosahexaenoic (DHA), and arachidonic (ARA) acids and the omega-3 to omega-6 ratio in plasma, liver, and blood leukocytes. Kruskal-Wallis and Wilcoxon tests were applied to plasma and liver data and descriptive analysis to leukocyte data. Results: Plasma, liver, and leukocytes exhibited almost undetectable EPA and DHA and detectable ARA concentrations at baseline. Immediately after FOLE infusion (T0), these PUFAs changed in all pools, resulting in a higher ratio of omega-3 to omega-6 compared with rats with no FOLE infusion (P < 0.05). All these changes decreased over time, with residual effects remaining until T6 in plasma, T12 in liver, and only until T2 in leukocytes. Conclusion: Data from this study suggest that omega-3 PUFAs are cleared early after the end of FOLE infusion, mainly in leukocytes. This should be considered when FOLEs are applied for immunomodulatory purposes in surgery.
- Influence of Intestinal Microbiota on Body Weight Gain: a Narrative Review of the Literature(2015) CARDINELLI, Camila S.; SALA, Priscila C.; ALVES, Claudia C.; TORRINHAS, Raquel S.; WAITZBERG, Dan L.In recent decades, experimental and clinical studies have associated the development of obesity with the composition of the gut microbiota. Mechanisms potentially involved in the contribution of gut microbiota to body weight gain include changes in energy extraction from the diet and the modulation of lipid metabolism, endocrine functions, and the immune system. The host's specific genetic heritage, the type and amount of food intake, chronic inflammation, reduced body energy expenditure, and exposure to obesogenic pollutants are also potential contributing factors. The pathophysiological processes involved in the relationship between gut microbiota and obesity are not fully understood, and further studies are needed to establish whether differences in gut bacterial diversity between obese and normal body weight individuals are the cause or a consequence of obesity.
- Effects of parenteral fish oil lipid emulsions on colon morphology and cytokine expression after experimental colitis(2013) GARIB, Ricardo; GARLA, Priscila; TORRINHAS, Raquel S.; BERTEVELLO, Pedro L.; LOGULLO, Angela F.; WAITZBERG, Dan L.Aim: To study the effects of different protocols of fish oil lipid emulsion (FOLE) infusion on acute inflammation in a rat model of colitis. Methods: Adult male Wistar rats (n = 51) were randomized into 5 groups to receive parenteral infusion of saline (SS) or soybean oil lipid emulsion (SO), as controls, and FOLE composed of: fish oil alone (FO); a mixture (9:1 v/v) of SO with FO (SO/FO); or 30% soybean oil, 30% medium-chain triglycerides, 25% olive oil, and 15% fish oil (SMOF). After 72 h of intravenous infusion, experimental colitis was induced with acetic acid. After 24 h, colonic samples were analyzed for histological and cytokine changes. Results: In relation SS group, macroscopic necrosis was less frequent in the FO group and histological necrosis was more frequent in the SMOF group. There was a direct and inverse relation of colon interleukin (IL)-1 and IL-4 respectively, with histological necrosis. In comparison to the SS group, FO increased IL-4 and IFN-gamma and decreased TNF-alpha, SO/FO decreased TNF-alpha, and SMOF increased IL-1 and decreased IL-4. Conclusion: In acetic acid-induced colitis, the isolate infusion of FOLE composed of fish oil alone was more advantageous in mitigating inflammation than the infusion of FOLE containing other oils, and this difference may be due the influences of their different fatty acid contents.
- Effect of parenteral infusion of fish oil-based lipid emulsion on systemic inflammatory cytokines and lung eicosanoid levels in experimental acute pancreatitis(2017) GARLA, Priscila; GARIB, Ricardo; TORRINHAS, Raquel S.; MACHADO, Marcel C. C.; CALDER, Philip C.; WAITZBERG, Dan L.Parenteral fish oil lipid emulsion (FOLE) might mitigate inflammation after injury. Acute pancreatitis (AP) can occur following major surgery and is characterized by tissue and systemic release of inflammatory mediators that contributes to the systemic inflammatory response syndrome and multiple organ failure. Aim: We evaluated the effect of short-term FOLE infusion before experimental induction of AP on systemic cytokine and lung eicosanoid profiles. Methods: Lewis rats (n = 72) received parenteral infusion of FOLE (FO group) or saline (SS group), or remained without parenteral infusion (CG group) for 48 h. Thereafter, AP was induced by retrograde injection of sodium taurocholate into the pancreatic duct. Animals were sacrificed after 2, 12 and 24 h. Blood and lung samples were collected to assess serum inflammatory cytokines (Luminex) and tissue eicosanoids (ELISA), respectively. Results: Serum TNF-alpha increased over time and serum IL-10 decreased from 12 to 24 h in CG group. In SS group serum TNF-alpha increased from 12 to 24 h (p = 0.039) and serum IL-10 decreased over time. Both CG and SS groups exhibited increased IL-6/IL-10 ratio (p = 0.040). From 12 to 24 h animals from FO group showed decreased serum IL-1 (p < 0.001), IL-4 (p < 0.002) and IL-6 (p = 0.050), and a trend towards increased IL-10 (p = 0.060). All experimental groups showed a trend towards increased PGE(2) and decreased LTB4 in the lung at 24 compared with 12 h Conclusion: Parenteral infusion of FOLE for 48 h before the induction of experimental AP appears to favorably influence the cytokine response without affecting lung eicosanoids at the time points measured. The use of FOLE to prevent and treat AP following major surgery needs to be further explored.
- Parenteral fi sh oil: An adjuvant pharmacotherapy for coronavirus disease 2019?(2021) TORRINHAS, Raquel S.; CALDER, Philip C.; LEMOS, Gabriela O.; WAITZBERG, Dan L.The new coronavirus associated with severe acute respiratory syndrome (SARS-CoV-2), surprisingly, does not affect only the lungs. The severe response to SARS-CoV-2 appears to include a ""cytokine storm,"" which indicates a state of hyperinflammation and subsequent dysfunction of multiple organs and tissues in the most severe cases. This could be the reason why populations at the highest risk for death from the SARS-CoV-2 infection-induced disease (coronavirus disease 2019 [COVID-19]) are those suffering from chronic lowgrade inflammation, but prone to hyperinflammation. This includes individuals of advanced age and those with obesity, type 2 diabetes, hypertension, and metabolic syndrome. Inflammation resolution is strongly dependent on lipid mediators, the specialized pro-resolution mediators (SPMs). oi-3 polyunsaturated fatty acids (oi-3 PUFAs) are precursors of very potent SPMs, including resolvins, protectins, and maresins. Additionally, they are associated with a less aggressive inflammatory initiation, after competing with oi-6 fatty acids for eicosanoid synthesis. Therefore, it makes sense to consider the use of oi-3 PUFAs for clinical management of COVID-19 patients. oi-3 PUFAs may be given by oral, enteral, or parenteral routes; however, the parenteral route favors faster incorporation into plasma phospholipids, blood cells, and tissues. Here, we discuss these aspects to propose the parenteral infusion of oi-3 PUFAs as adjuvant immunopharmacotherapy for hospitalized patients with COVID-19.
- SARS-CoV-2 infection, gut dysbiosis, and heterogeneous clinical results of hydroxychloroquine on COVID-19 therapy & mdash;Is there a link?(2021) BALMANT, Bianca D.; TORRINHAS, Raquel S.; ROCHA, Ilanna M.; FONSECA, Danielle C.; FORMIGA, Francisco F. C.; BONFA, Eloisa S. D. O.; BORBA, Eduardo F.; WAITZBERG, Dan L.Clinical manifestations of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can include gastrointestinal signals and symptoms. Individuals with previous clinical conditions that usually enroll gut dysbiosis have been identified as being at high risk to develop more severe infectious phenotypes. Actually, intestinal dysbiosis has been observed in infected patients and potentially linked to systemic hyper-inflammation. These observations suggest that a previous gut dysbiosis may be aggravated by SARS-CoV-2 infection and related to progression of the coronavirus disease 2019 (COVID-19) into more severe stages. While COVID-19 & rsquo;s pathophysiology is not fully understood, it seems relevant to consider the interactions of candidate therapeutic drugs with the host, gut microbiota, and SARS-CoV-2. Here we summarize scientific evidence supporting the potential relevance of these interactions and suggest that unfavorable clinical data on hydroxychloroquine administration in COVID-19 may have been influenced by the dose provided and its impact on gut dysbiosis. The proposition is based on preliminary data on gut microbiota composition from individuals with inactive systemic lupus erythematosus under exclusive continuous hydroxychloroquine treatment, displaying a direct correlation between drug doses and markers typically associated with gut dys-biosis.