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
11 resultados
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- 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.
- Increased intestinal production of alpha-defensins in aged rats with acute pancreatic injury(2014) CUNHA, Debora Maria Gomes; KOIKE, Marcia Kiyomi; BARBEIRO, Denise Frediani; BARBEIRO, Hermes Vieira; HAMASAKI, Mike Yoshio; COELHO NETO, Guilherme Tude; MACHADO, Marcel Cerqueira Cesar; SILVA, Fabiano Pinheiro daAcute pancreatitis is a life-threatening situation, frequently associated with uncontrolled local and systemic inflammation, and aging is associated with a worst prognosis. Antimicrobial peptides are ancient molecules that belong to innate immunity, produced by epithelial and immune cells, and are able to trigger a myriad of effector responses. We have hypothesized that antimicrobial peptides could play an important role during serious pancreatic injury. To investigate our hypothesis, alpha-defensin-5, alpha-defensin-7 and CRAMP gene expression levels were measured in the intestinal tissue of old and young rats submitted to chemical pancreatic damage. We found significantly higher levels of alpha-defensin-5 and alpha-defensin-7, but not CRAMP, in the samples from old mice. This increase was not associated with a worse systemic inflammatory response. We conclude that alpha-defensins may have a pivotal role during acute pancreatitis and that the elderly develops a more severe local, but not systemic inflammatory process.
- Neuropeptides in the brain defense against distant organ damage(2016) HAMASAKI, Mike Yoshio; BARBEIRO, Hermes Vieira; BARBEIRO, Denise Frediani; CUNHA, Debora Maria Gomes; KOIKE, Marcia Kiyomi; MACHADO, Marcel Cerqueira Cesar; SILVA, Fabiano Pinheiro daDelirium, or acute confusional state, is a common manifestation in diseases that originate outside the central nervous system, affecting 30-40% of elderly hospitalized patients and up to 80% of the critically ill, even though it remains unclear if severe systemic inflammation is able or not to induce cellular disturbances and immune activation in the brain. Neuropeptides are pleotropic molecules heterogeneously distributed throughout the brain and possess a wide spectrum of functions, including regulation of the inflammatory response, so we hypothesized that they would be the major alarm system in the brain before overt microglia activation. In order to investigate this hypothesis, we induced acute pancreatitis in 8-10 week old rats and collected brain tissue, 12 and 24 h following pancreatic injury, to measure neuropeptide and cytokine tissue levels. We found significantly higher levels of beta-endorphin, orexin and oxytocin in the brain of rats submitted to pancreatic injury, when compared to healthy controls. Interestingly, these differences were not associated with increased local cytokine levels, putting in evidence that neuropeptide release occurred independently of microglia activation and may be a pivotal alarm system to initiate neurologic reactions to distant inflammatory non-infectious aggression.
conferenceObject Decrease of CC-Family Chemokines Levels in the Heart Tissue of Aged Rats Following Severe Acute Pancreatitis: A New Mechanism of Heart Protection During Systemic Inflammation(2016) AMARAL, Rizia C.; BARBEIRO, Denise F.; KOIKE, Marcia K.; SILVA, Fabiano P.; MACHADO, Marcel C.- Intestinal barrier dysfunction and increased COX-2 gene expression in the gut of elderly rats with acute pancreatitis(2016) BARBEIRO, Denise Frediani; KOIKE, Marcia Kiyomi; COELHO, Ana Maria Mendonca; SILVA, Fabiano Pinheiro da; MACHADO, Marcel Cerqueira CesarBackground/Objectives: The clinical course of acute pancreatitis can vary from mild to severe. In its most severe manifestation, acute pancreatitis is associated with an exacerbated systemic inflammatory response and high mortality rates. The severe form of acute pancreatitis is more frequent in elderly patients than in young patients, but the mechanisms underlying this difference are still under investigation. Methods: Rats were divided into two groups as follows: Group 1, young rats; and Group 2, old rats. Acute pancreatitis group was induced by a retrograde injection of a sodium taurocholate solution into the biliopancreatic duct. Using this model of acute pancreatic injury, we designed a study to investigate possible differences in microbial translocation and characteristics of the intestinal barrier between elderly and young rats. Results: There was a significantly higher number of bacterial colonies in the pancreas of elderly rats compared with young rats following pancreas injury, which was associated with a more severe local intestinal inflammatory response that included elevated gene expression of COX-2 and a decreased gene expression of tight junction proteins. Conclusions: We conclude that intestinal damage during acute pancreatitis is exacerbated in elderly rats compared with young rats and that COX-2 inhibition could be a potential therapeutic target to offer tailored treatment for acute pancreatitis in the elderly.
- Cytokine and chemokine levels in the heart tissue of aged rats following severe acute pancreatitis(2017) AMARAL, Rizia Callou; BARBEIRO, Denise Frediani; KOIKE, Marcia Kiyomi; MADY, Charles; MACHADO, Marcel Cerqueira Cesar; SILVA, Fabiano Pinheiro daSevere acute pancreatitis (AP) is a disease associated with high mortality and characterized by overwhelming systemic inflammation. Older people have a prolonged hospital stay and worst prognosis, when affected by this disease. Our group hypothesized, thus, that the systemic inflammatory response in the elderly would promote more organ damage when compared to the young. We sought to investigate the effect of systemic inflammation on the gene expression of cytokines, chemokines, and growth factors in the hearts of older and younger rats in an animal model of AP. AP was induced in all rats by injection of 0.5 mL of 2.5% taurocholate. There were two healthy age-matched control groups. An array of 79 cytokines, chemokines, and growth factors was measured in samples of cardiac tissue taken from the AP rats after 10 h, and from control rats. Older healthy rats had significantly higher levels of interleukin-10 (IL-10) and CCL1 gene expression than younger ones (P < 0.05), but all other measurements were similar among the study groups. This study indicates the systemic inflammation may show unique features for different organs in the body, but older animals with systemic inflammation are similar to the young regarding the cardiac inflammatory response.
conferenceObject Increased TNF alpha Levels in the Intestinal Tissue, but Not in the Brain, Following Severe Acute Pancreatitis(2015) HAMASAKI, Mike Yoshio; BARBEIRO, Hermes Vieira; BARBEIRO, Denise Frediani; CUNHA, Debora Maria Gomes; KOIKE, Marcia Kiyomi; MACHADO, Marcel Cerqueira Cesar; SILVA, Fabiano Pinheiro da- Does fasting protect liver from ischemia and reperfusion injury?(2023) KOIKE, Marcia Kiyomi; BARBEIRO, Denise Frediani; SOUZA, Heraldo Possolo de; MACHADO, Marcel Cerqueira CesarPurpose: To evaluate local and systemic effects of 24-hour fasting in liver ischemia and reperfusion injury. Methods: Twenty-one adult male Wistar rats (330-390 g) were submitted to 60 minutes of hepatic ischemia followed by 24 hours of reperfusion. Before the day of the experiment, the animals fasted, but free access to water was allowed. Two groups were constituted: Control: nonfasted, that is, feeding ad libitum before surgical procedure; Fasting: rats underwent previous fasting of 24 hours. Hepatic ischemia was performed using vascular clamp in hepatic pedicle. At 24 hours after liver reperfusion, blood and tissue samples were collected. To analysis, liver lobes submitted to ischemia was identified as ischemic liver and paracaval non-ischemic lobes as non-ischemic activities, and both ratio), cytokines (interleukins-6, -10, and tumor necrosis factor-alpha), hepatic ischemia and reperfusion injury (histology). Results: Malondialdehyde measured in non-ischemic and ischemic liver samples, hepatocellular function and cytokines were comparable between groups. Histological findings were distinct in three regions evaluated. Microvesicular steatosis was comparable between 24-hour fasting and non-fasted control groups in periportal region of hepatic lobe. In contrast, steatosis was more pronounced in zones 2 and 3 of ischemic liver samples of fasting compared to control groups. Conclusion: These data indicates that fasting does not protect, but it can be also detrimental to liver submitted to ischemia/reperfusion damage. At that time, using long fasting before liver surgery in the real world may be contraindicated.
- Short-Term Effects of Sepsis and the Impact of Aging on the Transcriptional Profile of Different Brain Regions(2019) HAMASAKI, Mike Yoshio; SEVERINO, Patricia; PUGA, Renato David; KOIKE, Marcia Kiyomi; HERNANDES, Camila; BARBEIRO, Hermes Vieira; BARBEIRO, Denise Frediani; MACHADO, Marcel Cerqueira Cesar; REIS, Eduardo Moraes; SILVA, Fabiano Pinheiro daAmong the clinical manifestations observed in septic patients, sepsis-associated encephalopathy (SAE) is probably the most obscure and poorly explored. It is well established, however, that SAE is more prevalent in aged individuals and related to a worse outcome. In this context, we decided to investigate the acute effects of sepsis, induced by cecal ligation and puncture (CLP), on the cerebral transcriptional profile of young and old rats. The idea was to highlight important signaling pathways possibly implicated in the early stages of SAE. Global gene expression analysis of three different brain regions (hippocampus, cerebellum, and cortex) indicated a relatively small interference of sepsis at the transcriptional level. Cerebellum tissue was the least affected by sepsis in aged rats. The increased expression of S100a8, Upp1, and Mt2a in all three brain regions of young septic rats indicate that these genes may be involved in the first line of response to sepsis in the younger brain. On the other hand, altered expression of a network of genes involved in sensory perception of smell in the cortex of aged rats, but not in young ones, indicates an earlier disruption of cortex function, possibly more sensitive to the systemic inflammation. The expression of S100a8 at the protein level was confirmed in all brain regions, with clear-up regulation in septic aged cortex. Taken together, our results indicate that the transcriptional response of the central nervous system to early sepsis varies between distinct brain regions and that the cortex is affected earlier in aged animals, in line with early neurological manifestations observed in older patients.