JOSE PINHATA OTOCH
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Cirurgia, Faculdade de Medicina - Docente
DVCLCIR-62, Hospital Universitário
LIM/26 - Laboratório de Pesquisa em Cirurgia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
DVCLCIR-62, Hospital Universitário
LIM/26 - Laboratório de Pesquisa em Cirurgia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
15 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 15
- A novel supplement with yeast 6-glucan, prebiotic, minerals and Silybum marianum synergistically modulates metabolic and inflammatory pathways and improves steatosis in obese mice(2021) NEHMI, Victor Abou; MURATA, Gilson Masahiro; MORAES, Ruan Carlos Macedo de; LIMA, Gabriely Cristina Alves; MIRANDA, Danielle Araujo De; RADLOFF, Katrin; COSTA, Raquel Galvao Figueredo; JESUS, Joyce de Cassia Rosa de; FREITAS, Jessica Alves De; VIANA, Nayara Izabel; PIMENTA, Ruan; LEITE, Katia Ramos Moreira; OTOCH, Jose Pinhata; PESSOA, Ana Flavia MarcalObjective: To evaluate the synergic effects of a novel oral supplement formulation, containing prebiotics, yeast beta-glucans, minerals and silymarin (Silybum marianum), on lipid and glycidic metabolism, inflammatory and mitochondrial proteins of the liver, in control and high-fat diet-induced obese mice. Methods: After an acclimation period, 32 male C57BL/6 mice were divided into the following groups: nonfat diet (NFD) vehicle, NFD supplemented, high-fat diet (HFD) vehicle and HFD supplemented. The vehicle and experimental formulation were administered orally by gavage once a day during the last four weeks of the diet (28 consecutive days). We then evaluated energy homeostasis, inflammation, and mitochondrial protein expression in these groups of mice. Results: After four weeks of supplementation, study groups experienced reduced glycemia, dyslipidemia, fat, and hepatic fibrosis levels. Additionally, proliferator-activated receptor-alpha, AMP-activated protein kinase-1 alpha, peroxisome proliferator-activated receptor c co-activator-1 alpha, and mitochondrial transcription factor A expression levels were augmented; however, levels of inhibitor of nuclear factor-kappa B kinase subunit a and p65 nuclear factor-kappa B expression, and oxidative markers were reduced. Notably, the cortisol/C-reactive protein ratio, a well-characterized marker of the hypothalamic-pituitary-adrenal axis immune interface status, was found to be modulated by the supplement. Conclusion: We discovered that the novel supplement was able to modify different antioxidant, metabolic and inflammatory pathways, improving the energy homeostasis and inflammatory status, and consequently alleviated hepatic steatosis.
- Effect of Duodenal-Jejunal Bypass Surgery on Glycemic Control in Type 2 Diabetes: A Randomized Controlled Trial(2015) PETRY, Tarissa Z.; FABBRINI, Elisa; OTOCH, Jose P.; CARMONA, Murilo A.; CARAVATTO, Pedro P.; SALLES, Joao E.; SARIAN, Thais; CORREA, Jose L.; SCHIAVON, Carlos A.; PATTERSON, Bruce W.; COHEN, Ricardo; KLEIN, SamuelObjectiveTo determine whether upper gastrointestinal tract (UGI) bypass itself has beneficial effects on the factors involved in regulating glucose homeostasis in patients with type 2 diabetes (T2D). MethodsA 12-month randomized controlled trial was conducted in 17 overweight/obese subjects with T2D, who received standard medical care (SC, n=7, BMI=31.73.5 kg/m(2)) or duodenal-jejunal bypass surgery with minimal gastric resection (DJBm) (n=10; BMI=29.71.9 kg/m(2)). A 5-h modified oral glucose tolerance test was performed at baseline and at 1, 6, and 12 months after surgery or starting SC. ResultsBody weight decreased progressively after DJBm (7.9 +/- 4.1%, 9.6 +/- 4.2%, and 10.2 +/- 4.3% at 1, 6, and 12 months, respectively) but remained stable in the SC group (P<0.001). DJBm, but not SC, improved: (1) oral glucose tolerance (decreased 2-h glucose concentration, P=0.039), (2) insulin sensitivity (decreased homeostasis model assessment of insulin resistance, P=0.013), (3) early insulin response to a glucose load (increased insulinogenic index, P=0.022), and (4) overall glycemic control (reduction in HbA1c with fewer diabetes medications). ConclusionsDJBm causes moderate weight loss and improves metabolic function in T2D. However, our study cannot separate the benefits of moderate weight loss from the potential therapeutic effect of UGI tract bypass itself on the observed metabolic improvements.
- Adipose tissue inflammation and cancer cachexia: Possible role of nuclear transcription factors(2012) BATISTA JR., M. L.; PERES, S. B.; MCDONALD, M. E.; ALCANTARA, P. S. M.; OLIVAN, M.; OTOCH, J. P.; FARMER, S. R.; SEELAENDER, M.Cancer cachexia is a multifaceted syndrome whose aetiology is extremely complex and is directly related to poor patient prognosis and survival. Changes in lipid metabolism in cancer cachexia result in marked reduction of total fat mass, increased lipolysis, total oxidation of fatty acids, hyperlipidaemia, hypertriglyceridaemia, and hypercholesterolaemia. These changes are believed to be induced by inflammatory mediators, such as tumour necrosis factor-alpha (TNF-alpha) and other factors. Attention has recently been drawn to the current theory that cachexia is a chronic inflammatory state, mainly caused by the host's reaction to the tumour. Changes in expression of numerous inflammatory mediators, notably in white adipose tissue (WAT), may trigger several changes in WAT homeostasis. The inhibition of adipocyte differentiation by PPAR gamma is paralleled by the appearance of smaller adipocytes, which may partially account for the inhibitory effect of PPAR gamma on inflammatory gene expression. Furthermore, inflammatory modulation and/or inhibition seems to be dependent on the IKK/NF-kappa B pathway, suggesting that a possible interaction between NF-kappa B and PPAR gamma is required to modulate WAT inflammation induced by cancer cachexia. In this article, current literature on the possible mechanisms of NF-kappa B and PPAR gamma regulation of WAT cells during cancer cachexia are discussed. This review aims to assess the role of a possible interaction between NF-kappa B and PPAR gamma in the setting of cancer cachexia as well as its significant role as a potential modulator of chronic inflammation that could be explored therapeutically. Crown
- EUS-guided Choledochoduodenostomy Versus Hepaticogastrostomy A Systematic Review and Meta-analysis(2018) UEMURA, Ricardo S.; KHAN, Muhammad Ali; OTOCH, Jose P.; KAHALEH, Michel; MONTERO, Edna F.; ARTIFON, Everson L. A.Background and Aims: Endoscopic ultrasound-guided biliary drainage (EUS-BD) has emerged as an alternative in cases of endoscopic retrograde cholangiopancreatography (ERCP) failure. Two types of EUS-BD methods for achieving biliary drainage when ERCP fails are choledochoduodenostomy (CDS) or hepaticogastrostomy (HGS). However, there is no consensus if one approach is better than the other. Therefore, we conducted a systematic review and meta-analysis to evaluate these 2 main EUS-BD methods. Methods: We searched MEDLINE, Embase, Scopus, Cochrane database, LILACS from inception through April 8, 2017, using the following search terms in various combinations: biliary drainage, biliary stent, transluminal biliary drainage, choledochoduodenostomy, hepaticogastrostomy, endoscopic ultrasound-guided biliary drainage. We selected studies comparing CDS and HGS in patients with malignant biliary obstruction with ERCP failure. Pooled odds ratio (OR) were calculated for technical success, clinical success, and adverse events and difference of means calculated for duration of procedure and survival after procedure. Results: A total of 10 studies with 434 patients were included in the meta-analysis: 208 underwent biliary drainage via HGS and the remaining 226 via CDS. The technical success for CDS and HGS was 94.1% and 93.7%, respectively, pooled OR = 0.96 [95% confidence interval (CI) = 0.39-2.33, I-2 = 0%]. Clinical success was 88.5% in CDS and 84.5% in HGS, pooled OR = 0.76 (95% CI = 0.42-1.35, I-2 = 17%). There was no difference for adverse events OR = 0.97 (95% CI = 0.60-1.56), I-2 = 37%. CDS was about 2 minutes faster with a pooled difference in means of was -2.69 (95% CI = -4.44 to -0.95). Conclusion: EUS-CDS and EUS-HGS have equal efficacy and safety, and are both associated with a very high technical and clinical success. The choice of approach may be selected based on patient anatomy.
- Hepaticogastrostomy or choledochoduodenostomy for distal malignant biliary obstruction after failed ERCP: Is there any difference?(2015) ARTIFON, Everson L. A.; MARSON, Fernando P.; GAIDHANE, Monica; KAHALEH, Michel; OTOCH, Jose P.Background: EUS-guided biliary drainage (BD) is an evolving alternative technique for patients with malignant biliary obstruction for which ERCP failed. Objective: To compare the outcomes of 2 nonanatomic EUS-guided BD routes: hepaticogastrostomy (HPG) and choledochoduodenostomy (CD). Design: Prospective, randomized trial. Setting: Tertiary endoscopic referral center. Patients: Forty-nine patients with unresectable distal malignant biliary obstruction and failed ERCP were included. The HPG group had 25 patients and the CD group had 24 patients. Interventions: EUS-guided HPG or CD. In all procedures, a biliary puncture with a 19-gauge needle followed by cholangiography, wire advancement, track dilation, and self-expandable metal stent deployment were performed. Main Outcome Measurements: Technical and clinical success, quality of life, adverse events, and survival. Results: The technical success rate was 96% for HPG and 91% for CD. The clinical success rate was 91% for HPG and 77% for CD. The mean procedural time was 47.8 minutes for HPG and 48.8 minutes for CD. The mean scores of quality of life were similar during follow-up. The overall adverse event rate was 16.3% (20% for the HPG group and 12.5% for the CD group). One patient with a bile leak required percutaneous biloma drainage. There was no statistical difference between the 2 techniques and no difference with regard to survival time between the 2 groups. Limitations: Single-center study. Conclusion: HPG and CD techniques are similar in efficacy and safety. Both HPG and CD seem valid alternative options for BD in patients with distal malignant biliary obstruction after failed ERCP.
- Tumour-derived transforming growth factor-beta signalling contributes to fibrosis in patients with cancer cachexia(2019) LIMA, Joanna D. C. C.; SIMOES, Estefania; CASTRO, Gabriela de; MORAIS, Mychel Raony P. T.; MATOS-NETO, Emidio M. de; ALVES, Michele J.; I, Nelson Pinto; FIGUEREDO, Raquel G.; ZORN, Telma M. T.; FELIPE-SILVA, Aloisio S.; TOKESHI, Flavio; OTOCH, Jose P.; ALCANTARA, Paulo; CABRAL, Fernanda J.; FERRO, Emer S.; LAVIANO, Alessandro; SEELAENDER, MariliaBackground Cachexia is a paraneoplastic syndrome related with poor prognosis. The tumour micro-environment contributes to systemic inflammation and increased oxidative stress as well as to fibrosis. The aim of the present study was to characterise the inflammatory circulating factors and tumour micro-environment profile, as potentially contributing to tumour fibrosis in cachectic cancer patients. Methods 74 patients (weight stable cancer n = 31; cachectic cancer n = 43) diagnosed with colorectal cancer were recruited, and tumour biopsies were collected during surgery. Multiplex assay was performed to study inflammatory cytokines and growth factors. Immunohistochemistry analysis was carried out to study extracellular matrix components. Results Higher protein expression of inflammatory cytokines and growth factors such as epidermal growth factor, granulocyte-macrophage colony-stimulating factor, interferon-alpha, and interleukin (IL)-8 was observed in the tumour and serum of cachectic cancer patients in comparison with weight-stable counterparts. Also, IL-8 was positively correlated with weight loss in cachectic patients (P = 0.04; r = 0.627). Immunohistochemistry staining showed intense collagen deposition (P = 0.0006) and increased presence of alpha-smooth muscle actin (P < 0.0001) in tumours of cachectic cancer patients, characterizing fibrosis. In addition, higher transforming growth factor (TGF)-beta 1, TGF-beta 2, and TGF-beta 3 expression (P = 0.003, P = 0.05, and P = 0.047, respectively) was found in the tumour of cachectic patients, parallel to p38 mitogen-activated protein kinase alteration. Hypoxia-inducible factor-1 alpha mRNA content was significantly increased in the tumour of cachectic patients, when compared with weight-stable group (P = 0.005). Conclusions Our results demonstrate TGF-beta pathway activation in the tumour in cachexia, through the (non-canonical) mitogen-activated protein kinase pathway. The results show that during cachexia, intratumoural inflammatory response contributes to the onset of fibrosis. Tumour remodelling, probably by TGF-beta-induced transdifferentiation of fibroblasts to myofibroblasts, induces unbalanced inflammatory cytokine profile, angiogenesis, and elevation of extracellular matrix components (EMC). We speculate that these changes may affect tumour aggressiveness and present consequences in peripheral organs.
- Systemic Inflammation in Cachexia - Is Tumor Cytokine Expression Profile the Culprit?(2015) MATOS-NETO, Emidio M. de; LIMA, Joanna D. C. C.; PEREIRA, Welbert O. de; FIGUEREDO, Raquel G.; RICCARDI, Daniela M. dos R.; RADLOFF, Katrin; NEVES, Rodrigo X. das; CAMARGO, Rodolfo G.; MAXIMIANO, Linda F.; TOKESHI, Flavio; OTOCH, Jose P.; GOLDSZMID, Romina; CAMARA, Niels O. S.; TRINCHIERI, Giorgio; ALCANTARA, Paulo S. M. de; SEELAENDER, MariliaCachexia affects about 80% of gastrointestinal cancer patients. This multifactorial syndrome resulting in involuntary and continuous weight loss is accompanied by systemic inflammation and immune cell infiltration in various tissues. Understanding the interactions among tumor, immune cells, and peripheral tissues could help attenuating systemic inflammation. Therefore, we investigated inflammation in the subcutaneous adipose tissue and in the tumor, in weight stable and cachectic cancer patients with same diagnosis, in order to establish correlations between tumor microenvironment and secretory pattern with adipose tissue and systemic inflammation. Infiltrating monocyte phenotypes of subcutaneous and tumor vascular-stromal fraction were identified by flow cytometry. Gene and protein expression of inflammatory and chemotactic factors was measured with qRT-PCR and Multiplex Magpix (R) system, respectively. Subcutaneous vascular-stromal fraction exhibited no differences in regard to macrophage subtypes, while in the tumor, the percentage of M2 macrophages was decreased in the cachectic patients, in comparison to weight-stable counterparts. CCL3, CCL4, and IL-I beta expression was higher in the adipose tissue and tumor tissue in the cachectic group. In both tissues, chemotactic factors were positively correlated with IL-1 beta. Furthermore, positive correlations were found for the content of chemoattractants and cytokines in the tumor and adipose tissue. The results strongly suggest that the crosstalk between the tumor and peripheral tissues is more pronounced in cachectic patients, compared to weight-stable patients with the same tumor diagnosis.
- Comparative anatomical analysis of the transcallosal-transchoroidal and transcallosal-transforniceal-transchoroidal approaches to the third ventricle(2017) ARAUJO, Joao Luiz Vitorino; VEIGA, Jose C. E.; WEN, Hung Tzu; ANDRADE, Almir F. de; TEIXEIRA, Manoel J.; OTOCH, Jose P.; RHOTON JR., Albert L.; PREUL, Mark C.; SPETZLER, Robert F.; FIGUEIREDO, Eberval G.OBJECTIVE Access to the third ventricle is a veritable challenge to neurosurgeons. In this context, anatomical and morphometric studies are useful for establishing the limitations and advantages of a particular surgical approach. The transchoroidal approach is versatile and provides adequate exposure of the middle and posterior regions of the third ventricle. However, the fornix column limits the exposure of the anterior region of the third ventricle. There is evidence that the unilateral section of the fornix column has little effect on cognitive function. This study compared the anatomical exposure afforded by the transforniceal-transchoroidal approach with that of the transchoroidal approach. In addition, a morphometric evaluation of structures that are relevant to and common in the 2 approaches was performed. METHODS The anatomical exposure provided by the transcallosal-transchoroidal and transcallosal-transforniceal-transchoroidal approaches was compared in 8 fresh cadavers, using a neuronavigation system. The working area, microsurgical exposure area, and angular exposure on the longitudinal and transversal planes of 2 anatomical targets (tuber cinereum and cerebral aqueduct) were compared. Additionally, the thickness of the right frontal lobe parenchyma, thickness of the corpus callosum trunk, and longitudinal diameter of the interventricular foramen were measured. The values obtained were submitted to statistical analysis using the Wilcoxon test. RESULTS In the quantitative evaluation, compared with the transchoroidal approach, the transforniceal-transchoroidal approach provided a greater mean working area (transforniceal-transchoroidal 150 +/- 11 mm(2); transchoroidal 121 8 mm(2); p < 0.05), larger mean microsurgical exposure area (transforniceal-transchoroidal 101 9 mm(2); transchoroidal 80 +/- 5 mm(2); p < 0.05), larger mean angular exposure area on the longitudinal plane for the tuber cinereum (transforniceal-transchoroidal 71 degrees +/- 7 degrees; transchoroidal 64 degrees +/- 6 degrees; p < 0.05), and larger mean angular exposure area on the longitudinal plane for the cerebral aqueduct (transforniceal-transchoroidal 62 degrees +/- 6 degrees; transchoroidal 55 degrees +/- 5 degrees; p < 0.05). No differences were observed in angular exposure along the transverse axis for either anatomical target (tuber cinereum and cerebral aqueduct; p > 0.05). The mean thickness of the right frontal lobe parenchyma was 35 +/- 3 mm, the mean thickness of the corpus callosum trunk was 10 +/- 1 mm, and the mean longitudinal diameter of the interventricular foramen was 4.6 +/- 0.4 mm. In the qualitative assessment, it was noted that the transforniceal-transchoroidal approach led to greater exposure of the third ventricle anterior region structures. There was no difference between approaches in the exposure of the structures of the middle and posterior region. CONCLUSIONS The transforniceal-transchoroidal approach provides greater surgical exposure of the third ventricle anterior region than that offered by the transchoroidal approach. In the population studied, morphometric analysis established mean values for anatomical structures common to both approaches.
- Histologic, histochemical, and biomechanical properties of fragments isolated from the anterior wall of abdominal aortic aneurysms(2014) MONTEIRO, Jose Augusto Tavares; SILVA, Erasmo Simao da; RAGHAVAN, Madhavan L.; PUECH-LEAO, Pedro; HIGUCHI, Maria de Lourdes; OTOCH, Jose PinhataObjective: To analyze biomechanical, histologic, and histochemical properties of anterior fragments of abdominal aortic aneurysms (AAA) and to correlate them with the maximum transverse diameter (MTD) and symptoms associated to the aneurysms. Methods: Fragments of the anterior aneurysm wall were obtained from 90 patients submitted to open repair of AAA of degenerative etiology from 2004 to 2009 in the Clinics Hospital of Sao Paulo University Medical School. Two specimens were produced from the fragments: one for histologic analysis for quantification of collagen fibers, elastic fibers, smooth muscle cells, and degree of inflammatory activity and the other for uniaxial tensile test to assess biomechanical failure properties of the material, such as strength, tension, and stress. Cases were classified according to symptoms and to the AAA MTD. Results: Fragments from AAA with MTD >= 5.5 cm showed higher values for biomechanical failure properties than those of AAA with MTD < 5.5 cm (strength, 5.32 +/- 2.07 x 4.1 +/- 2.41 N; tension, 13.83 +/- 5.58 x 10.82 +/- 6.48 N/cm; stress, 103.02 x 77.03 N/cm(2); P < .05). No differences were observed between the groups in relation to failure strain (0.41 +/- 0.12 x 0.37 +/- 0.14; P = .260) and thickness of the fragments (1.58 +/- 0.41 x 1.53 +/- 0.42 mm; P = .662). The average values of fiber compositions of all the fragments were as follows: collagen fibers, 44.34 +/- 0.48% and 61.85 +/- 10.14% (Masson trichrome staining and Picrosirius red staining, respectively); smooth muscle cells, 3.46 +/- 2.23% (immunohistochemistry/alpha-actin); and elastic fibers, less than 1% (traces) (Verhoeff-van Gieson staining). No differences in fiber percentages (collagen, elastic, and smooth muscle) were observed in fragments from AAA with MTD >= 5.5 cm and <5.5 cm, but more intense inflammatory activity was seen in larger AAA (grade 3; 70% x 28.6%; P = .011). Compared with asymptomatic aneurysms, symptomatic aneurysms showed no differences in the biomechanical failure properties (strength, 5.32 +/- 2.36 x 4.65 +/- 2.05 N; P = .155; tension, 14.08 +/- 6.11 x 12.81 +/- 5.77 N/cm; P = .154; stress, 103.02 x 84.76 N/cm(2); P = .144), strain (0.38 +/- 0.12 x 0.41 +/- 0.13; P = .287), thickness of the fragments (1.56 +/- 0.41 x 1.57 +/- 0.41 mm; P = .848), and histologic composition (collagen fibers, 44.67 +/- 11.17 x 44.02 +/- 13.79%; P = .808; smooth muscle fibers, 2.52 x 2.35%; P = .751; elastic fibers, <1%) Conclusions: Fragments of the anterior wall from larger aneurysms were more resistant than those from smaller AAA, with no tissue properties that could explain this phenomenon in the histologic or histochemical analyses utilized.
- Photodynamic Therapy (PDT), Radiofrequency Ablation (RFA) With Biliary Stents in Palliative Treatment of Unresectable Extrahepatic Cholangiocarcinoma A Systematic Review and Meta-analysis(2022) MOHAN, Babu P.; CHANDAN, Saurabh; KHAN, Shahab R.; KASSAB, Lena L.; PONNADA, Suresh; ARTIFON, Everson L. A.; OTOCH, Jose P.; MCDONOUGH, Stephanie; ADLER, Douglas G.Background and Aim: Extrahepatic unresectable cholangiocarcinoma carries a dismal prognosis. In addition to biliary drainage by stent placement; photodynamic therapy (PDT) and radiofrequency ablation (RFA) have been tried to prolong survival. In this meta-analysis, we appraise the current known data on the use of PDT, RFA in the palliative treatment of extrahepatic unresectable cholangiocarcinoma. Methods: We searched multiple databases from inception through July 2020 to identify studies that reported on PDT and RFA. Pooled rates of survival, stent patency, 30-, 90-day mortality, and adverse events were calculated. Study heterogeneity was assessed using I (2)% and 95% prediction interval. Results: A total of 55 studies (2146 patients) were included. A total of 1149 patients underwent treatment with PDT (33 studies), 545 with RFA (22 studies), and 452 patients with stent-only strategy. The pooled survival rate with PDT, RFA, and stent-only groups was 11.9 [95% confidence interval (CI): 10.7-13.1] months, 8.1 (95% CI: 6.4-9.9) months, and 6.7 (95% CI: 4.9-8.4) months, respectively. The pooled time of stent patency with PDT, RFA, and stent-only groups was 6.1 (95% CI: 4.2-8) months, 5.5 (95% CI: 4.2-6.7) months, and 4.7 (95% CI: 2.6-6.7) months, respectively. The pooled rate of 30-day mortality with PDT was 3.3% (95% CI: 1.6%-6.7%), with RFA was 7% (95% CI: 4.1%-11.7%) and with stent-only was 4.9% (95% CI: 1.7%-13.1%). The pooled rate of 90-day mortality with PDT was 10.4% (95% CI: 5.4%-19.2%) and with RFA was 16.3% (95% CI: 8.7%-28.6%). Conclusion: PDT seemed to demonstrate better overall survival and 30-day mortality rates than RFA and/or stent-only palliation.