MARCIA KIYOMI KOIKE
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina
61 resultados
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- Effects of diazoxide in experimental acute necrotizing pancreatitis(2017) ANDRADE, Roberta de Oliveira; KUNITAKE, Tiago; KOIKE, Marcia Kiyomi; MACHADO, Marcel C. C.; SOUZA, Heraldo PossoloOBJECTIVE: We aimed to assess the effects of diazoxide on the mortality, pancreatic injury, and inflammatory response in an experimental model of acute pancreatitis. METHODS: Male Wistar rats (200-400 g) were divided randomly into two groups. Fifteen minutes before surgery, animals received physiological (0.9%) saline (3 mL/kg) (control group) or 45 mg/kg diazoxide (treatment group) via the intravenous route. Acute pancreatitis was induced by injection of 2.5% sodium taurocholate via the biliopancreatic duct. Mortality (n= 38) was observed for 72 h and analyzed by the Mantel-Cox Log-rank test. To study pancreatic lesions and systemic inflammation, rats (10 from each group) were killed 3 h after acute pancreatitis induction; ascites volume was measured and blood as well as pancreases were collected. Pancreatic injury was assessed according to Schmidt's scale. Cytokine expression in plasma was evaluated by the multiplex method. RESULTS: Mortality at 72 h was 33% in the control group and 60% in the treatment group (p = 0.07). Ascites volumes and plasma levels of cytokines between groups were similar. No difference was observed in edema or infiltration of inflammatory cells in pancreatic tissues from either group. However, necrosis of acinar cells was lower in the treatment group compared to the control group (3.5 vs. 3.75, p = 0.015). CONCLUSIONS: Treatment with diazoxide can reduce necrosis of acinar cells in an experimental model of acute pancreatitis, but does not affect the inflammatory response or mortality after 72 h.
- Exercise training program based on minimum weekly frequencies: effects on blood pressure and physical fitness in elderly hypertensive patients(2012) MORAES, Wilson M. De; SOUZA, Pamella R. M.; PINHEIRO, Monica H. N. P.; IRIGOYEN, Maria C.; MEDEIROS, Alessandra; KOIKE, Marcia K.Background: Exercise training (ET) can reduce blood pressure (BP) and prevent functional disability. However, the effects of low volumes of training have been poorly studied, especially in elderly hypertensive patients. Objectives: To investigate the effects of a multi-component ET program (aerobic training, strength, flexibility, and balance) on BP, physical fitness, and functional ability of elderly hypertensive patients. Methods: Thirty-six elderly hypertensive patients with optimal clinical treatment underwent a multi-component ET program: two 60-minute sessions a week for 12 weeks at a Basic Health Unit. Results: Compared to pre-training values, systolic and diastolic BP were reduced by 3.6% and 1.2%, respectively (p < 0.001), body mass index was reduced by 1.1% (p < 0.001), and peripheral blood glucose was reduced by 2.5% (p= 0.002). There were improvements in all physical fitness domains: muscle strength (chair-stand test and elbow flexor test; p < 0.001), static balance test (unipedal stance test; p < 0.029), aerobic capacity (stationary gait test; p < 0.001), except for flexibility (sit and reach test). Moreover, there was a reduction in the time required to perform two functional ability tests: ""put on sock"" and ""sit down, stand up, and move around the house"" (p < 0.001). Conclusions: Lower volumes of ET improved BP, metabolic parameters, and physical fitness and reflected in the functional ability of elderly hypertensive patients. Trial Registration RBR-2xgjh3.
- Diazoxide reduces local and remote organ damage in a rat model of intestinal ischemia reperfusion(2018) DOURADO, Saulo Fernandes de Mattos; BARBEIRO, Denise Frediani; KOIKE, Marcia Kiyomi; BARBEIRO, Hermes Vieira; SILVA, Fabiano Pinheiro da; MACHADO, Marcel Cerqueira CesarBackground: Intestinal ischemia reperfusion is a common clinical condition that causes functional impairment. Once tight junctions are damaged, barrier function is compromised, and the intestines become a source for entry of bacterial and inflammatory mediators into the circulation, leading to systemic inflammatory response syndrome, multiple organ failure, and death. It is possible that diazoxide could protect the intestines against ischemia reperfusion. The aim of this study is to determine whether diazoxide can provide protection in a rat model of intestinal ischemia reperfusion. Methods: A total of 32 adult male specific pathogen-free Wistar rats were randomized into three groups: a control group, n = 6; a saline group, n = 13; and a diazoxide group, n = 13. The saline and diazoxide groups underwent clamping of the superior mesenteric artery for 1 h, with samples in all the groups being collected 12 h later. Results: Intestinal histology showed greater damage in the intestinal ischemia reperfusion groups. mRNA expression of zonula occludens-1 and occludin (tight junction proteins) and interleukin-6 and cyclooxygenase-2 was the highest in the Saline group. The Diazoxide group showed a reduction in aspartate aminotransferase serum levels compared with the other groups. Conclusions: Increased expression of zonula occludens-1, occludin, and cyclooxygenase-2 suggested a greater regenerative effort because ofmore severe lesions in the saline group. In addition, increased expression of interleukin-6 in the saline group was suggestive of inflammation, indicating that diazoxide had protective effects in the diazoxide group. Reduced aspartate aminotransferase in the diazoxide group suggested liver protection. Diazoxide protects the intestines and liver fromintestinal ischemia reperfusion lesions in rats.
- Sodium Taurocholate Induced Severe Acute Pancreatitis in C57BL/6 Mice(2021) SERRA, Mariana B.; KOIKE, Marcia K.; BARBEIRO, Denise F.; MACHADO, Marcel C. C.; SOUZA, Heraldo P. deBiliary acute pancreatitis induction by sodium taurocholate infusion has been widely used by the scientific community due to the representation of the human clinical condition and reproduction of inflammatory events corresponding to the onset of clinical biliary pancreatitis. The severity of pancreatic damage can be assessed by measuring the concentration, speed, and volume of the infused bile acid. This study provides an updated checklist of the materials and methods used in the protocol reproduction and shows the main results from this acute pancreatitis (AP) model. Most of the previous publications have limited themselves to reproducing this model in rats. We have applied this method in mice, which provides additional advantages (i.e., the availability of an arsenal of reagents and antibodies for these animals along with the possibility of working with genetically modified strains of mice) that may be relevant to the study. For acute pancreatitis induction in mice, we present a systematic protocol, with a defined dose of 2.5% sodium taurocholate at an infusion speed 10 mu L/min for 3 min in C57BL/6 mice that reaches its maximal level of severity within 12 h of induction and highlight results with outcomes that validate the method. With practice and technique, the total estimated time, from the induction of anesthesia to the completion of the infusion, is 25 min per animal.
conferenceObject Bilateral Inguinal Hernia Repair and Male Fertility: A Randomized Clinical Trial Comparing Lichtenstein vs Laparoscopic Transabdominal Preperitoneal(2022) DAMOUS, Sergio H. B.; DAMOUS, Luciana L.; BORGES, Victor A.; FONTELLA, Amanda K.; MIRANDA, Jocielle S.; KOIKE, Marcia K.; SAITO, Osmar C.; BIROLINI, Claudio A. V.; UTIYAMA, Edivaldo M.- Bilateral inguinal hernia repair and male fertility: a randomized clinical trial comparing Lichtenstein versus laparoscopic transabdominal preperitoneal (TAPP) technique(2023) DAMOUS, Sergio Henrique Bastos; DAMOUS, Luciana Lamarao; BORGES, Victor Andre; FONTELLA, Amanda Karsburg; MIRANDA, Jocielle dos Santos; KOIKE, Marcia Kiyomi; SAITO, Osmar Cassio; BIROLINI, Claudio Augusto Vianna; UTIYAMA, Edivaldo MassazoBackground The effects of hernia repair on testicular function remain uncertain, regardless of the technique used. Studies that analyze testicular volume and flow after hernia repair or hormonal measurements are scarce and show contradictory results. This study aimed to evaluate the impact of bilateral inguinal hernia repair on male fertility in surgical patients in whom the Lichtenstein and laparoscopic transabdominal preperitoneal (TAPP) techniques were used.Methods A randomized clinical trial comparing open (Lichtenstein) versus laparoscopic (TAPP) hernia repair using polypropylene mesh was performed in 48 adult patients (20 to 60 years old) with primary bilateral inguinal hernia. Patients were evaluated preoperatively and 90 and 180 postoperative (PO) days. Sex hormones (Testosterone, FSH, LH and SHGB) analysis, testicular ultrasonography, semen quality sexual activity changes and quality of life (QoL) were performed. Postoperative pain was evaluated using the visual analog scale (VAS).Results Thirty-seven patients with aged of 44 +/- 11 years were included, 19 operated on Lichtenstein and 18 operated on TAPP. The surgical time was similar between techniques. The pain was greater in the Lichtenstein group on the 7th PO day. The biochemical and hormonal analyses, testicular ultrasonography (Doppler, testicular volume, and morphological findings) and sperm quality were similar between groups. However, the sperm morphology was better in the Lichtenstein group after 180 days (p < 0.05 vs. preoperative) and two patients who underwent Lichtenstein hernia repair had oligospermia after 180 days. The QoL evaluation showed a significant improvement after surgery in the following domains: physical function, role emotional, bodily pain and general health (p < 0.05). On comparison of Lichtenstein vs. TAPP none of the domains showed statistically significant differences. No patient reported sexual changes.Conclusion Bilateral inguinal hernia repair with polypropylene mesh, whether using Lichtenstein or TAPP, does not impair male fertility in terms of long-term outcomes.Trial registration: Approved by the Ethics Committee for the Analysis of Research Projects (CAPPesq) of the HC/FMUSP, Number 2.974.457, in June 2015, Registered on Plataforma Brasil in October 2015 under Protocol 45535015.4.0000.0068. Registered on Clinicaltrials.gov, NCT 05799742. Enrollment of the first subject in January 2016.
- Dietary interesterified fat enriched with palmitic acid induces atherosclerosis by impairing macrophage cholesterol efflux and eliciting inflammation(2016) AFONSO, Milessa Silva; LAVRADOR, Maria Silvia Ferrari; KOIKE, Marcia Kiyomi; CINTRA, Dennys Esper; FERREIRA, Fabiana Dias; NUNES, Valeria Sutti; CASTILHO, Gabriela; GIOIELLI, Luiz Antonio; BOMBO, Renata Paula; CATANOZI, Sergio; CALDINI, Elia Garcia; DAMACENO-RODRIGUES, Nilsa Regina; PASSARELLI, Marisa; NAKANDAKARE, Edna Regina; LOTTENBERG, Ana MariaInteresterified fats are currently being used to replace trans fatty acids. However, their impact on biological pathways involved in the atherosclerosis development was not investigated. Weaning male LDLr-KO mice were fed for 16 weeks on a high-fat diet (40% energy as fat) containing polyunsaturated (PUFA), TRANS, palmitic (PALM), palmitic interesterified (PALM INTER), stearic (STEAR) or stearic interesterified (STEAR INTER). Plasma lipids, lipoprotein profile, arterial lesion area, macrophage infiltration, collagen content and inflammatory response modulation were determined. Macrophage cholesterol efflux and the arterial expression of cholesterol uptake and efflux receptors were also performed. The interesterification process did not alter plasma lipid concentrations. Although PALM INTER did not increase plasma cholesterol concentration as much as TRANS, the cholesterol enrichment in the LDL particle was similar in both groups. Moreover, PALM INTER induced the highest IL-1 beta, MCP-1 and IL-6 secretion from peritoneal macrophages as compared to others. This inflammatory response elicited by PALM INTER was confirmed in arterial wall, as compared to PALM. These deleterious effects of PALM INTER culminate in higher atherosclerotic lesion, macrophage infiltration and collagen content than PALM, STEAR, STEAR INTER and PUFA. These events can partially be attributed to a macrophage cholesterol accumulation, promoted by apoAl and HDL2-mediated cholesterol efflux impairment and increased Olr-1 and decreased Abca1 and Nr1h3 expressions in the arterial wall. Interesterified fats containing palmitic acid induce atherosclerosis development by promoting cholesterol accumulation in LDL particles and macrophagic cells, activating the inflammatory process in LDLr-KO mice.
- Parathyroid hormone and phosphorus overload in uremia: impact on cardiovascular system(2012) CUSTODIO, Melani R.; KOIKE, Marcia K.; NEVES, Katia R.; REIS, Luciene M. dos; GRACIOLLI, Fabiana G.; NEVES, Carolina L.; BATISTA, Daniella G.; MAGALHAES, Andrea O.; HAWLITSCHEK, Philippe; OLIVEIRA, Ivone B.; DOMINGUEZ, Wagner V.; MOYSES, Rosa M. A.; JORGETTI, VandaBackground. Cardiac remodeling in uremia is characterized by left ventricular hypertrophy, interstitial fibrosis and microvascular disease. Cardiovascular disease is the leading cause of death in uremic patients, but coronary events alone are not the prevalent cause, sudden death and heart failure are. We studied the cardiac remodeling in experimental uremia, evaluating the isolated effect of parathyroid hormone (PTH) and phosphorus. Methods. Wistar rats were submitted to parathyroidectomy (PTx) and 5/6 nephrectomy (Nx); they also received vehicle (V) and PTH at normal (nPTH) or high (hPTH) doses. They were fed with a poor-phosphorus (pP) or rich-phosphorus (rP) diet and were divided into the following groups: 'Sham': G1 (V + normal-phosphorus diet (np)) and 'Nx + PTx': G2 (nPTH + pP), G3 (nPTH + rP), G4 (hPTH + pP) and G5 (hPTH + rP). After 8 weeks, biochemical analysis, myocardium morphometry and arteriolar morphological analysis were performed. In addition, using immunohistochemical analysis, we evaluated angiotensin II, alpha-actin, transforming growth factor-beta (TGF-beta) and nitrotyrosine, as well as fibroblast growth factor-23 (FGF-23), fibroblast growth factor receptor-1 (FGFR-1) and runt-related transcription factor-2 (Runx-2) expression. Results. Nx animals presented higher serum creatinine levels as well as arterial hypertension. Higher PTH levels were associated with myocardial hypertrophy and fibrosis as well as a higher coronary lesion score. High PTH animals also presented a higher myocardial expression of TGF-beta, angiotensin II, FGF-23 and nitrotyrosine and a lower expression of alpha-actin. Phosphorus overload was associated with higher serum FGF-23 levels and Runx-2, as well as myocardial hypertrophy. FGFR-1 was positive in the cardiomyocytes of all groups as well as in calcified coronaries of G4 and G5 whereas Runx-2 was positive in G3, G4 and G5. Conclusion. In uremia, PTH and phosphorus overload are both independently associated with major changes related to the cardiac remodeling process, emphasizing the need for a better control of these factors in chronic kidney disease.
conferenceObject Palmitic Interesterified Fat Induces Atherosclerosis and Inflammatory Cytokine Secretion in LDL Receptor Knockout Mice(2014) AFONSO, Milessa S.; LAVRADOR, Maria Silvia F.; KOIKE, Marcia; BOMBO, Renata P.; NUNES, Valeria S.; CATANOZI, Sergio; CASTILHO, Gabriela; PASSARELLI, Marisa; NAKANDAKARE, Edna R.; LOTTENBERG, Ana Maria- Acute aortocaval fistula: role of low perfusion pressure and subendocardial remodeling on left ventricular function(2013) MAZZO, Flavia R. R.; FRIMM, Clovis de Carvalho; MORETTI, Ana Iochabel S.; GUIDO, Maria C.; KOIKE, Marcia K.The experimental model of aortocaval fistula is a useful model of cardiac hypertrophy in response to volume overload. In the present study it has been used to investigate the pathologic subendocardial remodeling associated with the development of heart failure during the early phases (day 1, 3, and 7) following volume overload. Compared with sham treated rats, aortocaval fistula rats showed lower systemic blood pressure and higher left ventricular end-diastolic pressure This resulted in lower coronary driving pressure and left ventricular systolic and diastolic dysfunction. Signs of myocyte necrosis, leukocyte cell infiltration, fibroplasia and collagen deposition appeared sequentially in the subendocardium where remodeling was more prominent than in the non-subendocardium. Accordingly, increased levels of TNF-alpha, IL-1 beta, and IL-6, and enhanced MMP-2 activity were all found in the subendocardium of rats with coronary driving pressure 60mmHg. The coronary driving pressure was inversely correlated with MMP-2 activity in subendocardium in all time-points studied, and blood flow in this region showed positive correlation with systolic and diastolic function at day 7. Thus the predominant subendocardial remodeling that occurs in response to low myocardial perfusion pressure during the acute phases of aortocaval fistula contributes to early left ventricular dysfunction.