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
13 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 13
- Pain inhibition through transplantation of fetal neuronal progenitors into the injured spinal cord in rats(2019) BATISTA, Chary M.; MARIANO, Eric D.; DALE, Camila S.; CRISTANTE, Alexandre F.; BRITTO, Luiz R.; OTOCH, Jose P.; TEIXEIRA, Manoel J.; MORGALLA, Matthias; LEPSKI, GuilhermeNeuropathic pain after spinal cord injury (SCI) is a complex condition that responds poorly to usual treatments. Cell transplantation represents a promising therapy; nevertheless, the ideal cell type in terms of neurogenic potential and effectiveness against pain remains largely controversial. Here, we evaluated the ability of fetal neural stem cells (fNSC) to relieve chronic pain and, secondarily, their effects on motor recovery. Adult Wistar rats with traumatic SCI were treated, 10 days after injury, with intra-spinal injections of culture medium (sham) or fNSCs extracted from telencephalic vesicles (TV group) or the ventral medulla (VM group) of E/14 embryos. Sensory (von Frey filaments and hot plate) and motor (the Basso, Beattie, Bresnahan locomotor rating scale and inclined plane test) assessments were performed during 8 weeks. Thereafter, spinal cords were processed for immunofluorescence and transplanted cells were quantified by stereology. The results showed improvement of thermal hyperalgesia in the TV and VM groups at 4 and 5 weeks after transplantation, respectively. Moreover, mechanical allodynia improved in both the TV and VM groups at 8 weeks. No significant motor recovery was observed in the TV or VM groups compared with sham. Stereological analyses showed that similar to 70% of TV and VM cells differentiated into NeuN(+) neurons, with a high proportion of enkephalinergic and GABAergic cells in the TV group and enkephalinergic and serotoninergic cells in the VM group. Our study suggests that neuronal precursors from TV and VM, once implanted into the injured spinal cord, maturate into different neuronal subtypes, mainly GABAergic, serotoninergic, and enkephalinergic, and all subtypes alleviate pain, despite no significant motor recovery. The study was approved by the Animal Ethics Committee of the Medical School of the University of Sao Paulo (protocol number 033/14) on March 4, 2016.
- Virtual reality simulator versus box-trainer to teach minimally invasive procedures: A meta-analysis(2019) GUEDES, Hugo Goncalo; FERREIRA, Zemia Maria Camara Costa; LEAO, Layra Ribeiro de Sousa; MONTERO, Edna Frasson Souza; OTOCH, Jose Pinhata; ARTIFON, Everson Luiz de AlmeidaBackground: To evaluate the effectiveness of virtual reality simulator (VRS) training compared to box-trainer training (BT) for learning outcomes in minimally invasive surgery (MIS) techniques. Materials and Methods: A systematic review of the literature was performed using CENTRAL, MEDLINE, EMBASE, Scopus, CINAHL, LILACS. The primary outcomes were time to perform MIS and performance score in MIS. After being selected, the articles were evaluated for methodological quality and risk of bias. The results were evaluated for quality of evidence and meta-analysis was performed. Results: 20 randomized clinical trials were included in the qualitative analysis and 14 were used in the meta-analysis. VRS training was more efficient than BT training (P < 0.00001, 95% CI: 35.08 to -25.01) when evaluating participant time needed to complete the peg task. In descriptive analysis, VRS training was better than BT training in participant performance score to perform MIS. There was no statistical difference in the meta-analysis in the time needed to perform surgery, time to complete basic or advanced tasks and performance score for basic or advanced tasks. Conclusions: VRS training was better than BT training in participant performance scores when performing MIS and in the time needed to complete the basic task of peg transfer. In all other outcomes, regardless of the student's level of experience or type of activity, the two forms of training were equivalent.
- Characterization of traumatic spinal cord injury model in relation to neuropathic pain in the rat(2019) BATISTA, Chary Marquez; MARIANO, Eric Domingos; ONUCHIC, Fernando; DALE, Camila Squarzoni; SANTOS, Gustavo Bispo dos; CRISTANTE, Alexandre Fogaca; OTOCH, Jose Pinhata; TEIXEIR, Manoel Jacobsen; MORGALLA, Matthias; LEPSKI, GuilhermePurpose/aim: Neuropathic pain following spinal cord injury (SCI) has a tremendous impact on patient's quality of life, and frequently is the most limiting aspect of the disease. In view of the severity of this condition and the absence of effective treatments, the establishment of a reliable animal model that reproduces neuropathic pain after injury is crucial for a better understanding of the pathophysiology and for the development of new therapeutic strategies. Thus, the objective of the present study was to standardize the traumatic SCI model in relation to neuropathic pain.Materials and methods: Wistar rats were submitted to SCI of mild intensity (pendulum height 12.5mm) or moderate intensity (pendulum height 25mm) using the New York University Impactor equipment. Behavioural assessment was performed during 8weeks. Thereafter, spinal cords were processed for immunohistochemistry.Results: The animals of the moderate injury group in comparison with mild injury had a greater motor function deficit, worse mechanical allodynia, and latter bladder recovery; moreover, histological analysis revealed more extensive lesions with lower neuronal population.Conclusions: Our study suggests that moderate SCI causes a progressive and long-lasting painful condition (at least 8weeks), in addition to motor impairment, and thus represents a reliable animal model for the study of chronic neuropathic pain after SCI.
- Human Cachexia Induces Changes in Mitochondria, Autophagy and Apoptosis in the Skeletal Muscle(2019) CASTRO, Gabriela S. de; SIMOES, Estefania; LIMA, Joanna D. C. C.; ORTIZ-SILVA, Milene; FESTUCCIA, William T.; TOKESHI, Flivio; ALCANTARA, Paulo S.; OTOCH, Jose P.; COLETTI, Dario; SEELAENDER, MariliaCachexia is a wasting syndrome characterized by the continuous loss of skeletal muscle mass due to imbalance between protein synthesis and degradation, which is related with poor prognosis and compromised quality of life. Dysfunctional mitochondria are associated with lower muscle strength and muscle atrophy in cancer patients, yet poorly described in human cachexia. We herein investigated mitochondrial morphology, autophagy and apoptosis in the skeletal muscle of patients with gastrointestinal cancer-associated cachexia (CC), as compared with a weight-stable cancer group (WSC). CC showed prominent weight loss and increased circulating levels of serum C-reactive protein, lower body mass index and decreased circulating hemoglobin, when compared to WSC. Electron microscopy analysis revealed an increase in intermyofibrillar mitochondrial area in CC, as compared to WSC. Relative gene expression of Fission 1, a protein related to mitochondrial fission, was increased in CC, as compared to WSC. LC3 II, autophagy-related (ATG) 5 and 7 essential proteins for autophagosome formation, presented higher content in the cachectic group. Protein levels of phosphorylated p53 (Ser46), activated caspase 8 (Asp384) and 9 (Asp315) were also increased in the skeletal muscle of CC. Overall, our results demonstrate that human cancer-associated cachexia leads to exacerbated muscle-stress response that may culminate in muscle loss, which is in part due to disruption of mitochondrial morphology, dysfunctional autophagy and increased apoptosis. To the best of our knowledge, this is the first report showing quantitative morphological alterations in skeletal muscle mitochondria in cachectic patients.
bookPart Principais acessos em cirurgia inguinal(2019) MASSAROLO, Paulo; OTOCH, José Pinhata; JACOMO, Alfredo Luiz; HOJAIJ, Flávio Carneiro; ANDRADE, Mauro Figueiredo Carvalho debookPart Principais acessos em cirurgias abdominais(2019) OTOCH, José Pinhata; JACOMO, Alfredo Luiz; MASSAROLO, Paulo; HOJAIJ, Flávio Carneiro; ANDRADE, Mauro Figueiredo Carvalho debookPart Acessos cirúrgicos na região cervical(2019) HOJAIJ, Flávio Carneiro; JACOMO, Alfredo Luiz; ANDRADE, Mauro Figueiredo Carvalho de; AKAMATSU, Flavia Emi; MASSAROLLO, Paulo; OTOCH, José Pinhata- 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.
bookPart Acessos cirúrgicos na região torácica(2019) OTOCH, José Pinhata; ANDRADE, Mauro Figueiredo Carvalho de; HOJAIJ, Flávio Carneiro; AKAMATSU, Flavia Emi; JACOMO, Alfredo LuizbookPart Fasciotomias(2019) ANDRADE, Mauro Figueiredo Carvalho de; JACOMO, Alfredo Luiz; OTOCH, José Pinhata