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Made available in DSpace on 2018-12-11T17:35:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-11-01. Added 1 bitstream(s) on 2019-10-09T18:33:05Z : No. of bitstreams: 1 S0102-86502017001100964.pdf: 1022293 bytes, checksum: bbd0f73555fcb60693b965b2f9459e77 (MD5) Purpose: To investigate the effects of atenolol in inflammatory mediator and oxidative stress in a myocardial injury by intestinal ischemia/reperfusion in rat model. Methods: Adult Wistar male rats were randomly (n=8), anesthetized and divided in: Sham: submitted to operation only; group SS+IR: intravenous saline infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); group AT+IR: intravenous atenolol infusion (2 mg/kg) following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); and group AT+I+AT+R: intravenous atenolol infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and in the time 45 minutes other atenolol doses were administrated and the artery was open for 120 minutes (reperfusion), all animals were submitted to muscular relaxation for mechanical ventilation. In the end of experiment the animals were euthanized and the hearts tissue were morphology analyzed by histology and malondialdehyde by ELISA, and the plasma were analyzed for tumor necrosis factor-alpha by ELISA. Results: The group SS+IR demonstrated the higher malondialdehyde levels when compared with the atenolol treated-groups (p=0.001) in the heart tissue. The tumor necrosis factoralpha level in plasma decrease in the treated groups when compared with SS+IR group (p=0.001). Histology analyses demonstrate pyknosis, edema, cellular vacuolization, presence of inflammatory infiltrate and band contraction in the heart tissue of the rats. Conclusion: Atenolol significantly reduce the degree of cardiac damage after intestinal ischemia-reperfusion. Translational Medicine Universidade Federal de São Paulo (UNIFESP) Division of Anesthesia Pain and Intensive Medicine Department of Surgery UNIFESP UNIFESP Department of Pharmacology UNIFESP Veterinary Medicine School UNESP Division of Cardiology Department of Surgery UNIFESP Division of Anesthesia Pain and Intensive Medicine Department of Surgery and Translational Medicine UNIFESP Veterinary Medicine School UNESP

Objetivo:Avaliar a capacidade da clonidina de reduzir a pressão arterial pulmonar de pacientes com hipertensão pulmonar, submetidos a cirurgia cardíaca, seja pela diminuição dos valores pressóricos a partir da aferição direta da pressão de artéria pulmonar, seja pela redução ouabolição da necessidade de dobutamina e nitroprussiato de sódio no intraoperatório.Método:Trata-se de estudo controlado, comparativo, randomizado e duplamente encoberto feito com 30 pacientes portadores de hipertensão arterial pulmonar tipo 2, submetidos a cirurgia cardíaca. Avaliaram-se a pressão média de artéria pulmonar e a posologia de dobutaminae nitroprussiato de sódio em quatro momentos: (M0) antes da administração de 2 µg/kg declonidina intravenosa ou placebo; (M1) decorridos 30 minutos do tratamento testado e antes da circulação extracorpórea; (M2) imediatamente após a circulação extracorpórea; e (M3)10 minutos após a injeção de protamina.Resultados:Não houve diferenças significativas em relação à pressão média de artéria pulmonarem nenhum dos momentos estudados. Entre os grupos não houve também diferença significativa entre as demais variáveis estudadas, como pressão arterial sistêmica média, frequência cardíaca, dosagem total de dobutamina, dosagem total de nitroprussiato de sódio e necessidade do hipnoanalgésico fentanil.Conclusão:A análise dos dados obtidos dos pacientes incluídos neste estudo permite concluir que a clonidina, na dose de 2 µg/kg administrada via intravenosa, não foi capaz de reduzir a pressão média de artéria pulmonar de pacientes com hipertensão pulmonar do grupo 2 (hipertensão venosa pulmonar), submetidos a cirurgia cardíaca, e nem reduzir ou abolir a necessidade da administração de dobutamina e nitroprussiato de sódio no intraoperatório. Objective:Evaluate the ability of clonidine to reduce pulmonary arterial pressure in patients with pulmonary hypertension undergoing heart surgery, either by reducing the pressure values from the direct measurement of pulmonary arterial pressure or by reducing or eliminating the need for intraoperative dobutamine and nitroprusside.Method:Randomized, double-blind, placebo-controlled, comparative study conducted in 30 patients with pulmonary arterial hypertension type 2 undergoing cardiac surgery. Mean pulmonary arterial pressure and dosage of dobutamine and sodium nitroprusside were assessed four times: before intravenous administration of clonidine (2 µg/kg) or placebo (T0), 30 min after tested treatment and before cardiopulmonary bypass (T1), immediately after CPB (T2), 10 min after protamine injection (T3).Results:There were no significant differences regarding mean pulmonary arterial pressure at any time of evaluation. There was no significant difference between groups regarding other variables, such as mean systemic arterial pressure, heart rate, total dose of dobutamine, total dose of sodium nitroprusside, and need for fentanyl.Conclusion:Data analysis from patients included in this study allows us to conclude that intra-venous clonidine (2 µg/kg) was not able to reduce the mean pulmonary arterial pressure inpatients with pulmonary hypertension in group 2 (pulmonary venous hypertension), undergoing heart surgery, or reduce or eliminate the need for intraoperative administration of dobutamineand sodium nitroprusside. Objetivo:Evaluar la capacidad de la clonidina de reducir la presión arterial pulmonar de pacientes con hipertensión pulmonar sometidos a cirugía cardíaca, sea por la disminución de los valores tensionales a partir de la comprobación directa de la presión de la arteria pulmonar, o por la reducción o supresión de la necesidad de dobutamina y nitroprusiato de sodio en el intraoperatorio.Método:Se trata de un estudio controlado, comparativo, aleatorizado y doble ciego hecho con 30 pacientes con hipertensión arterial pulmonar tipo 2, sometidos a cirugía cardíaca. Fueron evaluados la presión promedio de la arteria pulmonar y la posología de dobutamina y nitroprusiato de sodio en 4 momentos: (M0) antes de la administración de 2 µg/kg de clonidina intravenosa o placebo; (M1) transcurridos 30 min del tratamiento testado y antes de la circulación extracorpórea; (M2) inmediatamente después de la circulación extracorpórea; y (M3) 10 min después de la inyección de protamina.Resultados:No fueron verificadas diferencias significativas con relación a la presión promedio de la arteria pulmonar en ninguno de los momentos estudiados. Entre los grupos tampoco hubo diferencia significativa entre las demás variables estudiadas, como presión arterial sistémica promedio, frecuencia cardíaca, dosificación total de dobutamina, dosificación total de nitroprusiato de sodio y la necesidad del hipnoanalgésico fentanilo.Conclusiones:El análisis de los datos obtenidos de los pacientes incluidos en este estudio permite concluir que la clonidina en una dosis de 2 µg/kg administrada por vía intravenosa no fue capaz de reducir la presión promedio de la arteria pulmonar de pacientes con hipertensión pulmonar del grupo 2 (hipertensión venosa pulmonar), sometidos a cirugía cardíaca, ni tampoco reducir o suprimir la necesidad de la administración de dobutamina y nitroprusiato de sodio en el intraoperatorio. Universidade Federal de São Paulo (UNIFESP) Hospital São Paulo Hospital Beneficência Portuguesa Universidade Federal de São Paulo (UNIFESP) UNIFESP, Hospital São Paulo UNIFESP SciELO

Objetivo: Avaliar a capacidade da clonidina de reduzir a pressão arterial pulmonar de pacientes com hipertensão pulmonar, submetidos a cirurgia cardíaca, seja pela diminuição dos valores pressóricos a partir da aferição direta da pressão de artéria pulmonar, seja pela redução ouabolição da necessidade de dobutamina e nitroprussiato de sódio no intraoperatório. Método: Trata-se de estudo controlado, comparativo, randomizado e duplamente encoberto feito com 30 pacientes portadores de hipertensão arterial pulmonar tipo 2, submetidos a cirurgia cardíaca. Avaliaram-se a pressão média de artéria pulmonar e a posologia de dobutaminae nitroprussiato de sódio em quatro momentos: (M0) antes da administração de 2 µg/kg declonidina intravenosa ou placebo; (M1) decorridos 30 minutos do tratamento testado e antes da circulação extracorpórea; (M2) imediatamente após a circulação extracorpórea; e (M3)10 minutos após a injeção de protamina. Resultados: Não houve diferenças significativas em relação à pressão média de artéria pulmonarem nenhum dos momentos estudados. Entre os grupos não houve também diferença significativa entre as demais variáveis estudadas, como pressão arterial sistêmica média, frequência cardíaca, dosagem total de dobutamina, dosagem total de nitroprussiato de sódio e necessidade do hipnoanalgésico fentanil. Conclusão: A análise dos dados obtidos dos pacientes incluídos neste estudo permite concluir que a clonidina, na dose de 2 µg/kg administrada via intravenosa, não foi capaz de reduzir a pressão média de artéria pulmonar de pacientes com hipertensão pulmonar do grupo 2 (hipertensão venosa pulmonar), submetidos a cirurgia cardíaca, e nem reduzir ou abolir a necessidade da administração de dobutamina e nitroprussiato de sódio no intraoperatório. Objective: Evaluate the ability of clonidine to reduce pulmonary arterial pressure in patients with pulmonary hypertension undergoing heart surgery, either by reducing the pressure values from the direct measurement of pulmonary arterial pressure or by reducing or eliminating the need for intraoperative dobutamine and nitroprusside. Method: Randomized, double-blind, placebo-controlled, comparative study conducted in 30 patients with pulmonary arterial hypertension type 2 undergoing cardiac surgery. Mean pulmonary arterial pressure and dosage of dobutamine and sodium nitroprusside were assessed four times: before intravenous administration of clonidine (2 µg/kg) or placebo (T0), 30 min after tested treatment and before cardiopulmonary bypass (T1), immediately after CPB (T2), 10 min after protamine injection (T3). Results: There were no significant differences regarding mean pulmonary arterial pressure at any time of evaluation. There was no significant difference between groups regarding other variables, such as mean systemic arterial pressure, heart rate, total dose of dobutamine, total dose of sodium nitroprusside, and need for fentanyl. Conclusion: Data analysis from patients included in this study allows us to conclude that intra-venous clonidine (2 µg/kg) was not able to reduce the mean pulmonary arterial pressure inpatients with pulmonary hypertension in group 2 (pulmonary venous hypertension), undergoing heart surgery, or reduce or eliminate the need for intraoperative administration of dobutamineand sodium nitroprusside. Objetivo: Evaluar la capacidad de la clonidina de reducir la presión arterial pulmonar de pacientes con hipertensión pulmonar sometidos a cirugía cardíaca, sea por la disminución de los valores tensionales a partir de la comprobación directa de la presión de la arteria pulmonar, o por la reducción o supresión de la necesidad de dobutamina y nitroprusiato de sodio en el intraoperatorio. Método: Se trata de un estudio controlado, comparativo, aleatorizado y doble ciego hecho con 30 pacientes con hipertensión arterial pulmonar tipo 2, sometidos a cirugía cardíaca. Fueron evaluados la presión promedio de la arteria pulmonar y la posología de dobutamina y nitroprusiato de sodio en 4 momentos: (M0) antes de la administración de 2 µg/kg de clonidina intravenosa o placebo; (M1) transcurridos 30 min del tratamiento testado y antes de la circulación extracorpórea; (M2) inmediatamente después de la circulación extracorpórea; y (M3) 10 min después de la inyección de protamina. Resultados: No fueron verificadas diferencias significativas con relación a la presión promedio de la arteria pulmonar en ninguno de los momentos estudiados. Entre los grupos tampoco hubo diferencia significativa entre las demás variables estudiadas, como presión arterial sistémica promedio, frecuencia cardíaca, dosificación total de dobutamina, dosificación total de nitroprusiato de sodio y la necesidad del hipnoanalgésico fentanilo. Conclusiones: El análisis de los datos obtenidos de los pacientes incluidos en este estudio permite concluir que la clonidina en una dosis de 2 µg/kg administrada por vía intravenosa no fue capaz de reducir la presión promedio de la arteria pulmonar de pacientes con hipertensión pulmonar del grupo 2 (hipertensión venosa pulmonar), sometidos a cirugía cardíaca, ni tampoco reducir o suprimir la necesidad de la administración de dobutamina y nitroprusiato de sodio en el intraoperatorio.

Resumen Objetivo Evaluar la capacidad de la clonidina de reducir la presion arterial pulmonar de pacientes con hipertension pulmonar sometidos a cirugia cardiaca, sea por la disminucion de los valores tensionales a partir de la comprobacion directa de la presion de la arteria pulmonar, o por la reduccion o supresion de la necesidad de dobutamina y nitroprusiato de sodio en el intraoperatorio. Metodo Se trata de un estudio controlado, comparativo, aleatorizado y doble ciego hecho con 30 pacientes con hipertension arterial pulmonar tipo 2, sometidos a cirugia cardiaca. Fueron evaluados la presion promedio de la arteria pulmonar y la posologia de dobutamina y nitroprusiato de sodio en 4 momentos: (M0) antes de la administracion de 2 μg/kg de clonidina intravenosa o placebo; (M1) transcurridos 30 min del tratamiento testado y antes de la circulacion extracorporea; (M2) inmediatamente despues de la circulacion extracorporea; y (M3) 10 min despues de la inyeccion de protamina. Resultados No fueron verificadas diferencias significativas con relacion a la presion promedio de la arteria pulmonar en ninguno de los momentos estudiados. Entre los grupos tampoco hubo diferencia significativa entre las demas variables estudiadas, como presion arterial sistemica promedio, frecuencia cardiaca, dosificacion total de dobutamina, dosificacion total de nitroprusiato de sodio y la necesidad del hipnoanalgesico fentanilo. Conclusiones El analisis de los datos obtenidos de los pacientes incluidos en este estudio permite concluir que la clonidina en una dosis de 2 μg/kg administrada por via intravenosa no fue capaz de reducir la presion promedio de la arteria pulmonar de pacientes con hipertension pulmonar del grupo 2 (hipertension venosa pulmonar), sometidos a cirugia cardiaca, ni tampoco reducir o suprimir la necesidad de la administracion de dobutamina y nitroprusiato de sodio en el intraoperatorio.

PURPOSE: To investigate the effects of ischemic preconditioning (IPC) on the expression of pro and anti-apoptotic genes in rat endothelial cells undergoing enteric ischemia (I) and reperfusion (R). METHODS: Thirty rats underwent clamping of the superior mesenteric vessels. Sham group (GS) laparotomy only; Ischemia (GI): intestinal ischemia (60 min); Ischemia and Reperfusion (GIR): ischemia (60 min) and reperfusion (120 min); Ischemia and intestinal ischemic preconditioning (GI + IPC) : 5 minutes of ischemia followed by 10 min of reperfusion before sustained ischemia (60 min) ischemia and reperfusion and IPC (GIR + IPC): 5 min ischemia followed by 10 min of reperfusion before sustained ischemia (60min) and reperfusion (120 min). Rat Endothelial Cell Biology (PCR array) to determine the expression of genes related to endothelial cell biology. RESULTS: Gene expression of pro-apoptotic markers (Casp1, Casp6, Cflar, Fas, and Pgl) was down regulated in GI+IPC and in GIR + IPC. In contrast, the expression of anti-apoptotic genes (Bcl2 and Naip2), was up-regulated in GI + IPC and in GIR + IPC. CONCLUSION: Ischemic preconditioning may protect against cell death caused by ischemia and reperfusion.

To examine whether treatment with L-arginine (ARG), a substrate of nitric oxide biosynthesis, attenuated intestinal dysfunction caused by ischemia (I) and reperfusion (R), we treated rats with ARG (100 mg/kg intravenously) or saline solution (SS) before 60 minutes of I produced by occlusion of the superior mesenteric artery and/or during 120 minutes of R. After I or I/R, we isolated 2-cm jejunal segments for mounting in an organ bath to study neurogenic contractions stimulated by electrical pulses or KCl with the use of a digital recording system. Thin jejunal slices were stained with hematoxylin and eosin for optical microscopy. Jejunal contractions were similar in the sham and I+ARG, but reduced in I+SS, I/R+SS, and I/R+ARG groups. Jejunal enteric nerves were damaged in I+SS, IR+SS, and IR+ARG, but not in the I+ARG group, suggesting that ARG attenuate intestinal dysfunctions due to I but not to R.

To study whether ischemic preconditioning (IPC) attenuated intestinal dysfunction caused by ischemia (I) and reperfusion (R), rats were underwent 60 minutes of I which was produced by occlusion of the superior mesenteric artery, and/or 120 minutes R. The IPC group had the I procedure previously stimulated for 5 minutes and the R for 10 minutes. IPC and sham groups were injected with saline solution (SS) via the femoral vein 5 minutes before the I and R, and for R. After I or I/R, 2-cm jejunal segments were mounted in an organ bath to study neurogenic contractions stimulated by electrical pulses or KCl using a digital recording system. Thin jejunal slices were stained with hematoxylin and eosin for optical microscopy. Compared with the sham group, jejunal contractions were similar in the IPC + I and the IPC + I/R groups, but reduced in the I + SS and the I/R + SS groups. The jejunal enteric nerves were damaged in the I + SS and the I/R + SS groups, but not in the IPC groups. These results suggested that ischemic preconditioning attenuated intestinal dysfunction caused by I and I/R.

A melatonina é um hormônio produzido pela glândula pineal, cuja secreção está diretamente relacionada ao ciclo claro-escuro. É um poderoso antioxidante e tem papel fundamental na regulação do estado sono/vigília, do ritmo de vários processos fisiológicos, participando do controle do relógio biológico, inclusive nos seres humanos. Ressalta-se que há evidências da sua ação no sistema genital feminino, influenciando a função ovariana e a fertilidade. De fato, este hormônio interage com esteróides sexuais, como o estrogênio, modificando a sinalização celular e a resposta no tecido alvo. Estudos clínicos sugerem que o tratamento com a melatonina interviria com a evolução de neoplasia-dependente do estrogênio. O objetivo dessa revisão é analisar as principais ações da melatonina no sistema neuroendócrino, no ciclo sono-vigília, no sistema imunológico, no sistema cardiovascular, bem como no sistema reprodutor. Melatonin is secreted by the pineal gland and this is linked to the day/night cycle. It is an antioxidant and plays a fundamental role in the regulation of the jet-lag stage, in several physiological reactions and in control of the biologic rhythm. Human melatonin has an important influence on the female genital system. In fact, melatonin may influence production and action of steroids, modifying cellular signalization on the target tissue. There are many evidences that the melatonin therapy may be interfering with neoplasia development, mainly of the estrogen-dependent tumor. This paper aims to analyze the actions of melatonin on the neuroendocrine, immunological and cardiovascular systems, as well as on the reproductive function.

Made available in DSpace on 2015-12-07T15:32:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2015. Added 1 bitstream(s) on 2015-12-07T15:52:46Z : No. of bitstreams: 1 PMC4517494.pdf: 1805761 bytes, checksum: 6cf8d72c78632ac401cdaaf2338314de (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) This investigation aimed to evaluate the occurrence of some apoptotic features induced by Leptospira interrogans serovar Icterohaemorrhagiae infection in young BALB/c mice during 2, 4, 7, 10, 14 and 21 days post-infection (dpi). The animals were euthanized and lung, liver and kidneys were harvested to histopathology analysis and immunohistochemistry to caspase-3 antigen detection was performed. Chromatin condensation in kidney and liver tissues, but not in lung tissue, was observed. Caspase-3 reactive cells, mainly characterized as renal epithelial cells, were detected in the days 14 and 21 at high levels when compared to days 2, 4 and 7 (p = 0.025; p

Mechanical ventilation with high tidal volumes (V T) has been shown to induce lung injury. We examined the hypothesis that this procedure induces lung injury with inflammatory features. Anesthetized male Wistar rats were randomized into three groups: group 1 (N = 12): V T = 7 ml/kg, respiratory rate (RR) = 50 breaths/min; group 2 (N = 10): V T = 21 ml/kg, RR = 16 breaths/min; group 3 (N = 11): V T = 42 ml/kg, RR = 8 breaths/min. The animals were ventilated with fraction of inspired oxygen of 1 and positive end-expiratory pressure of 2 cmH2O. After 4 h of ventilation, group 3, compared to groups 1 and 2, had lower PaO2 [280 (range 73-458) vs 517 (range 307-596), and 547 mmHg (range 330-662), respectively, P

To study if the treatment with adenosine (ADO), an agonist of adenosine receptors, attenuates intestinal dysfunction caused by ischemia (I) and reperfusion (R), we treated rabbits with ADO (15 mg · kg −1 , intravenously) or saline solution (SS) to I (60 minutes) before occlusion of superior mesenteric artery and/or R (120 min). After I or I/R, isolated jejunal segments (2 cm) were mounted in an organ bath to study nerve-mediated contractions stimulated by electrical pulses or KCl using a digital recording system. Thin jejunal slices were stained (hematoxylin and eosin) for analysis by optical microscopy. Compared to the sham group, the jejunal contractions were similar in I + ADO, but reduced in I + SS, I/R + SS, and I/R + ADO groups. We concluded that the jejunal enteric nerves were damaged in I + SS, I/R + SS, and I/R + ADO, but not in I + ADO group. These results suggested that ADO attenuated intestinal dysfunction due to I, but not to R.

Although assist ventilation with FIO2 0.21 is the preferable mode of ventilation in the intensive care unit, sometimes controlled ventilation with hyperoxia is needed. But the impact of this setting has not been extensively studied in elderly subjects. We hypothesized that a high fraction of inspired oxygen (FiO(2)) and controlled mechanical ventilation (CMV) is associated with greater deleterious effects in old compared to adult subjects. Adult and old rats were submitted to CMV with low tidal volume (6 ml/kg) and FiO(2) 1 during 3 or 6 h. Arterial blood gas samples were measured at 0, 60 and 180 min (four groups: old and adult rats, 3 or 6 h of CMV), and additionally at 360 min (two groups: old and adult rats, 6 h of CMV). Furthermore, total protein content (TPC) and tumor necrosis factor-alpha (TNF-α) in bronchoalveolar lavage were assessed; lung tissue was used for malondialdehyde and histological analyses, and the diaphragm for measurement of contractile function. Arterial blood gas analysis showed an initial (60 min) greater PaO(2) in elderly versus adult animals; after that time, elderly animals had lowers pH and PaO(2), and greater PaCO(2). After 3 h of CMV, TPC and TNF-α levels were higher in the old compared with the adult group (P 0.05). After 6 h of MV, malondialdehyde was significantly higher in elderly compared with the adult animals (P 0.05). Histological analysis showed leukocyte infiltration and edema, greater in old animals. In diaphragm, twitch contraction with caffeine significantly declined after 6 h of CMV only for the elderly group. These data support the hypothesis that relatively short-term CMV with low tidal volume and hyperoxia has greatest impact in elderly rats, decreasing diaphragmatic contractile function and increasing lung inflammation.

PURPOSE: To investigate the protective effects of pentoxifylline against lung injury observed after dorsal scald in aged animals. METHODS: Adult (eight months old) and aged (20 months old) rats were subjected to thermal injury or sham procedure. The six hours post-trauma animals received pentoxifylline and after 24 hours were euthanatized and lung tissue samples collectedted. The bronchoalveolar lavage fluid was evaluated for total protein content and tumor necrosis factor-alpha cytokine. Malondialdehyde and myeloperoxidase activety in the lung homogenate were measured and a histological lung examination was undertaken. RESULTS: Burn injury induced oxidative stress in lung homogenate was higher in elderly-burned rats compared to adult-burned rats (p

Acute respiratory distress syndrome secondary to sepsis is associated with high morbidity and mortality. The purpose of this study was to characterize the effects of ventilatory strategy and the modulating activity of pentoxifylline in a sepsis-induced lung dysfunction model. Male Wistar rats were randomly divided into six groups, undergoing two different ventilatory strategies. Rats received live Escherichia coli or saline intraperitoneally. After 6 hours, the septic animals were treated with either pentoxifylline (25 mg/kg for 20 minutes) or normal saline infusion and ventilated with low tidal volume (6 mL/kg; septic animals with E. coli intraperitoneal [IP] infusion, PTX-treated and ventilated with low tidal volume and septic animals with E. coli IP infusion and ventilated with low tidal volume, respectively) or high tidal volume (12 mL/kg; septic animals with E. coli IP infusion, PTX-treated and ventilated with high tidal volume and septic animals with E. coli IP infusion and ventilated with high tidal volume, respectively) for 3 hours. The control animals received normal saline infusion and, after 6 hours, were ventilated with low or high tidal volume (control animals with saline infusion and ventilated with low tidal volume and control animals with saline infusion and ventilated with high tidal volume, respectively). Lung dysfunctions were assessed by wet-to-dry lung ratios, total cell count, total protein, malondialdehyde, and tumor necrosis factor-alpha concentrations in bronchoalveolar lavage (BAL). Septic animals with E. coli IP infusion and ventilated with high tidal volume presented increased wet-to-dry lung ratios, total cell count, total protein, and malondialdehyde in BAL compared with the septic animals ventilated with low tidal volume. Septic animals treated with pentoxifylline presented higher arterial oxygenation and lower cellular influx, protein leakage, malondialdehyde concentration, and tumor necrosis factor-alpha levels in BAL compared with septic animals undergoing the same ventilatory support strategies (septic animals with E. coli IP infusion and ventilated with low tidal volume and septic animals with E. coli IP infusion and ventilated with high tidal volume). Ventilatory strategy modulated the inflammatory response and pulmonary alterations in a sepsis-induced acute lung injury model, and these effects are improved by pentoxifylline.

Made available in DSpace on 2022-04-28T20:52:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-01-01 Our aim was to evaluate the pulmonary changes induced by Leptospira interrogans infection in hamsters, and the gene expression of endogenous mediators in lung fragments during 28 days of observation. The animals were euthanized on days 4, 7, 14, 21, and 28 post-inoculation. Histopathologic lung analysis showed hemorrhage, pneumonia, alveolar congestion, and infiltrated cellular areas, with increasing severity until day 21 post-inoculation. Tumor necrosis factor (TNF)-α mRNA expression enhanced in first days with peak on day 4 and slightly decreased in the final phase. The interleukin (IL)-10 remained relatively constant throughout the period, with the exceptions of days 4 and 14. The endothelial nitric-oxide synthesis (eNOS) showed an increased expression on day 4, followed by an augment on days 7 and 14, and remaining constant up to day 28 post-infection. Our results demonstrate that inoculation of L. interrogans sorovar Icterohaemorrhagiae induced pulmonary lesions, including pulmonary hemorrhage, supporting that the lung is a target organ. Copyright © 2009 by The American Society of Tropical Medicine and Hygiene. Department of Animal Health and Production Microbiology Laboratory FOA Unesp-Estadual Paulista University, Araçatuba, São Paulo Inflammatory Mediators Laboratory Geriatrics and Gerontology Division Federal University of São Paulo Infectious Diseases Division Federal University of São Paulo Universidade Estadual Paulista-Unesp-FOA-Medicina Veterinária- Campus de Araçatuba, Rua Clóvis Pestana, 793, CEP: 16050-680, Araçatuba, São Paulo Microbiology Laboratory Estadual Paulista University Unesp-FOA-Campus Aracatuba, Rua Clóvis Pestana, 793, CEP: 16050-680, Araçatuba, São Paulo Inflammatory Mediators Laboratory Geriatrics and Gerontology Division Federal University, São Paulo Department of Animal Health and Production Estadual Paulista University Unesp-FOA-Campus de Araçatuba, São Paulo Department of Animal Health and Production Estadual Paulista University Unesp-FOA-Campus Araçatuba, São Paulo Infectious Diseases Division Federal University, São Paulo Department of Animal Health and Production Microbiology Laboratory FOA Unesp-Estadual Paulista University, Araçatuba, São Paulo Universidade Estadual Paulista-Unesp-FOA-Medicina Veterinária- Campus de Araçatuba, Rua Clóvis Pestana, 793, CEP: 16050-680, Araçatuba, São Paulo Microbiology Laboratory Estadual Paulista University Unesp-FOA-Campus Aracatuba, Rua Clóvis Pestana, 793, CEP: 16050-680, Araçatuba, São Paulo Department of Animal Health and Production Estadual Paulista University Unesp-FOA-Campus de Araçatuba, São Paulo Department of Animal Health and Production Estadual Paulista University Unesp-FOA-Campus Araçatuba, São Paulo

OBJETIVO: Analisar as alterações histomorfológicas e respiratórias em modelo de lesão pulmonar aguda por sepse em ratos tratados com pentoxifilina. MÉTODOS: Foram utilizados 15 ratos adultos distribuídos em três grupos (n=5, por grupo), assim constituídos: GC - receberam apenas ventilação mecânica; GS - Animais sépticos tratados com solução salina e mecanicamente ventilados; GS+PTX - Animais sépticos, com infusão de pentoxifilina e mecanicamente ventilados. Todos os animais foram ventilados por um período de 180 minutos. Ao final deste período, foram avaliadas variáveis gasométricas (gasometria arterial), gravimétricas (relação peso úmido/peso seco), concentração de proteínas totais no lavado broncoalveolar e histomorfométricas (espessura dos septos alveolares). Os dados obtidos foram submetidos a análise estatística (P < 0,05) RESULTADOS: A pressão parcial de oxigênio ao final do experimento mostrou-se elevada no grupo GS+PTX (460,0 ± 38,2 mmHg) em relação ao grupo GS (336,0 ± 14,6 mmHg) (P < 0,05). No grupo GS, a concentração de proteínas no lavado broncoalveolar encontrou-se aumentada em relação aos demais grupos; no entanto, se mostrou atenuada após a administração de pentoxifilina. Notamos, pela morfologia em todos os grupos avaliados, vasodilatação nos septos alveolares e no grupo S alguns alvéolos apresentaram-se repletos de macrófagos. Estes aspectos foram atenuados no GS+PTX. A espessura dos septos alveolares mostrou uma significante redução no grupo GS+PTX quando comparado com o grupo GS (P < 0,05). CONCLUSÃO: A pentoxifilina restabelece a oxigenação e reduz os efeitos deletérios do processo de sepse em associação à ventilação mecânica com baixo volume corrente. OBJECTIVE: Respiratory repercussion on acute lung injury in a model of induced sepsis intraperitoneally. METHODS: Fifteen animals taken at random were submitted to adult male Wistar rats. The rats were randomly divided into 3 groups (n=15): Group C - control group received only mechanical ventilation; Group S - rats received live Escherichia coli (E. coli) intraperitoneally (septic) and after 6 hours they were treated with normal saline infusion and ventilated with a low tidal volume. Group S+PTX - rats received live Escherichia coli intraperitoneally (septic) and after 6 hours they were treated with pentoxifylline (PTX) infusion and ventilated with a low tidal volume. All animals were ventilated during 180 minutes. We analyzed the arterial blood gases, gravimetric indices and histomorphometric analysis. RESULTS: Blood gases, wet to dry ratios, and total protein concentrations in the bronchoalveolar lavage were analyzed in all experimental groups. In the end of the experiment the partial pressure of oxygen was higher in the GS+PTX (460,0 ± 38,2 mmHg) compared with GS (336,0 ± 14,6 mmHg). Pentoxifylline with low tidal volume attenuated significantly total protein in the bronchoalveolar lavage. The septal diameter was significantly reduced in the group GS compared with group GS+PTX (P < 0,05). CONCLUSIONS:The pentoxifylline ameliorated the oxygenation and decreased the deleterious effects of sepsis in the associated mechanical ventilation.

PURPOSE: To compare the effectiveness of mechanical ventilation of supine versus prone position in hydrochloric acid (HCl)-induced lung dysfunction. METHODS: Twenty, adult, male, Wistar-EPM-1 rats were anesthetized and randomly grouped (n=5 animals per group) as follows: CS-MV (mechanical ventilation in supine position); CP-MV (mechanical ventilation in prone position); bilateral instillation of HCl and mechanical ventilation in supine position (HCl+S); and bilateral instillation of HCl and mechanical ventilation in prone position (HCl+P). All groups were ventilated for 180 minutes. The blood partial pressures of oxygen and carbon dioxide were measured in the time points 0 (zero; 10 minutes before lung injury for stabilization), and at the end of times acid injury, 60, 120 and 180 minutes of mechanical ventilation. At the end of experiment the animals were euthanized, and bronchoalveolar lavages (BALs) were taken to determine the contents of total proteins, inflammatory mediators, and lungs wet-to-dry ratios. RESULTS: In the HCl+P group the partial pressure of oxygen increased when compared with HCl+S (128.0±2.9 mmHg and 111.0±6.7 mmHg, respectively) within 60 minutes. TNF-α levels in BAL do not differ significantly in the HCl+P group (516.0±5.9 pg/mL), and the HCl+S (513.0±10.6 pg/mL). CONCLUSION: The use of prone position improved oxygenation, but did not reduce TNF-α in BAL upon lung dysfunction induced by HCl. OBJETIVO: Comparar os efeitos da ventilação mecânica em posição prona versus supina na disfunção pulmonar induzida por ácido clorídrico (HCl). MÉTODOS: Vinte ratos, adultos, Wistar-EPM-1 foram anestesiados e distribuídos aleatoriamente em grupos (n=5 animais por grupo): CS-MV (controle, ventilado mecanicamente em posição supina); CP-MV (controle, ventilado mecanicamente em posição prona); instilação bilateral de HCl e ventilação mecânica em posição supina (HCl+S) ou ventilação em posição prona (HCl+P). Todos os grupos foram submetidos a ventilação mecânica por 180 minutos. As pressões parciais de oxigênio e dióxido de carbono no sangue arterial foram mensuradas nos tempos Injúria ácida (10 minutos após instilação de HCl), e ao final de cada período após lesão por HCl, 60, 120 e 180 minutos sob ventilação mecânica. Ao final do experimento os animais foram eutanasiados, os pulmões retirados para avaliação do peso úmido em relação ao peso seco do pulmão direito e realizamos o lavado broncoalveolar (BAL) para determinação de proteínas totais e o mediador inflamatório TNF-α. RESULTADOS: No grupo HCl+P a pressão parcial de oxigênio, no tempo de 60 minutos, aumentou quando comparada com o grupo HCl+S (128.0±2.9 e 111.0±6.7 mmHg, respectivamente). Os níveis de TNF-α no lavado broncoalveolar não diferiram de maneira estatisticamente significante quando comparamos os grupos HCl+S (513.0±10.6 pg/mL) versus HCl+P (516.0±5.9 pg/mL). CONCLUSÃO: O uso da posição prona melhora a oxigenação, mas não reduz os níveis de BAL após disfunção pulmonar induzida por HCl.

Made available in DSpace on 2013-08-12T18:19:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-01-01 Made available in DSpace on 2013-09-30T18:25:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-01-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:42:54Z No. of bitstreams: 0 Made available in DSpace on 2014-05-20T13:42:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-01-01 Item merged in doublecheck by Felipe Arakaki (arakaki@reitoria.unesp.br) on 2015-12-11T19:04:29Z Item was identical to item(s): 14577, 70069 at handle(s): http://hdl.handle.net/11449/14915, http://hdl.handle.net/11449/70587 Leptospirosis is a public health problem worldwide and its etiology remains unclear. Its pathogenesis involves a complex interaction between host and infecting microorganism. The inflammatory reaction that controls the infection process also underscores many pathophysiological events occurring in leptospirosis. We investigated the presence of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in renal tissues by immunohistochemical and histopathological examination in animals experimentally inoculated with Leptospira serovar Canicola. All the tests were carried out 2, 7, 14, 21 or 28 days after inoculation. Although TNF-alpha and IL-6 had been detected in tissues throughout the observation period, these cytokines appeared more intensely during the initial phase of infection. Therefore, both TNF-alpha and IL-6 were associated with the immunopathogenesis of leptospirosis. This profile suggests a high immunocellular response throughout the early infection stages followed by subsequent humoral response. Univ Estadual Paulista, Sch Dent, FOA, Dept Anim Hlth & Prod, BR-16050680 Aracatuba, SP, Brazil Univ Estadual Paulista, Sch Dent, FOA, Dept Clin Surg & Anim Reprod, BR-16050680 Aracatuba, SP, Brazil Univ Fed São Paulo, Dept Med, Div Geriatr & Gerontol, Inflammatory Mediators Lab, São Paulo, Brazil Univ Estadual Paulista, Sch Dent, FOA, Dept Anim Hlth & Prod, BR-16050680 Aracatuba, SP, Brazil Univ Estadual Paulista, Sch Dent, FOA, Dept Clin Surg & Anim Reprod, BR-16050680 Aracatuba, SP, Brazil

Experimental models of sepsis-induced pulmonary alterations are important for the study of pathogenesis and for potential intervention therapies. The objective of the present study was to characterize lung dysfunction (low PaO2 and high PaCO2, and increased cellular infiltration, protein extravasation, and malondialdehyde (MDA) production assessed in bronchoalveolar lavage) in a sepsis model consisting of intraperitoneal (ip) injection of Escherichia coli and the protective effects of pentoxifylline (PTX). Male Wistar rats (weighing between 270 and 350 g) were injected ip with 10(7) or 10(9) CFU/100 g body weight or saline and samples were collected 2, 6, 12, and 24 h later (N = 5 each group). PaO2, PaCO2 and pH were measured in blood, and cellular influx, protein extravasation and MDA concentration were measured in bronchoalveolar lavage. In a second set of experiments either PTX or saline was administered 1 h prior to E. coli ip injection (N = 5 each group) and the animals were observed for 6 h. Injection of 10(7) or 10(9) CFU/100 g body weight of E. coli induced acidosis, hypoxemia, and hypercapnia. An increased (P0.05) cell influx was observed in bronchoalveolar lavage, with a predominance of neutrophils. Total protein and MDA concentrations were also higher (P0.05) in the septic groups compared to control. A higher tumor necrosis factor-alpha (P0.05) concentration was also found in these animals. Changes in all parameters were more pronounced with the higher bacterial inoculum. PTX administered prior to sepsis reduced (P0.05) most functional alterations. These data show that an E. coli ip inoculum is a good model for the induction of lung dysfunction in sepsis, and suitable for studies of therapeutic interventions.

PURPOSE: To develop a method of differential diagnosis to drowning, due to analysis of the alveolar macrophages quantitative, in rats submitted to induced drowning in fresh water and salty water. METHODS: Were used 15 male adult rats Wistar EPM-1, weight 360g (SD=21,3), randomized in three groups: G1- Control; G2- Fresh water; G3- Salty water, each one with n=5. The animals have been anesthetized and tracheostomized to insert a cannula inside the trachea, for drowning induction. The lungs have been removed, weighed, prepared for histology and colored by immunohistochemistry. The macrophages have been counted in both lungs (right and left) of each animal. The statistical test used was ANOVA (SPSS.10) with pG2>G1 with p=0,0001 in each comparison. The weight of lungs of G3 and G2 was higher than G1, with p>0,0001, however G3 and G2 do not possess difference statistics in the weight of lungs. CONCLUSION: The developed diagnostic method was efficient in rats. The results, if expanded, will be able to assist the Forensic Pathology for technique of low cost and high trustworthiness.

Tumor necrosis factor-alpha (TNF-alpha) is one of the most important proinflammatory cytokines which plays a central role in host defense and in the acute inflammatory response related to tissue injury. The major source of TNF-alpha are immune cells such as neutrophils and macrophages. We tested the hypothesis that pentoxifylline, a methylxanthine derivative, down-regulates proinflammatory cytokine expression during acute lung injury in rats. Male Wistar rats weighing 250 to 450 g were anesthetized ip with 50 mg/kg sodium thiopental and randomly divided into three groups: group 1 (N = 7): tidal volume (V T) = 7 ml/kg, respiratory rate (RR) = 50 breaths/min and normal saline infusion; group 2 (N = 7): V T = 42 ml/kg, RR = 9 breaths/min and normal saline infusion; group 3 (N = 7): V T = 42 ml/kg, RR = 9 breaths/min and pentoxifylline infusion. The animals were ventilated with an inspired oxygen fraction of 1.0, a positive end-expiratory pressure of 3 cmH2O, and normal saline or pentoxifylline injected into the left femoral vein. The mRNA of TNF-alpha rapidly increased in the lung tissue within 180 min of ventilation with a higher V T with normal saline infusion. The concentrations of inflammatory mediators were decreased in plasma and bronchoalveolar lavage (BAL) in the presence of higher V T with pentoxifylline infusion (TNF-alpha: plasma, 102.2 ± 90.9 and BAL, 118.2 ± 82.1; IL-1ß: plasma, 45.2 ± 42.7 and BAL, 50.2 ± 34.9, P < 0.05). We conclude that TNF-alpha produced by neutrophil influx may function as an alert signal in host defense to induce production of other inflammatory mediators. Universidade Federal de São Paulo (UNIFESP) Departamento de Doenças Infecciosas e Parasitárias Disciplina de Pneumologia Universidade Federal de São Paulo (UNIFESP) Departamento de Doenças Infecciosas e Parasitárias Laboratório de Ginecologia Molecular Universidade Federal de São Paulo (UNIFESP) Departamento de Doenças Infecciosas e Parasitárias Laboratório de Imunologia Universidade Estadual de Campinas Departamento de Clínica Médica Disciplina e Laboratório de Imunologia Clínica UNIFESP, Depto. de Doenças Infecciosas e Parasitárias Disciplina de Pneumologia UNIFESP, Depto. de Doenças Infecciosas e Parasitárias Laboratório de Ginecologia Molecular UNIFESP, Depto. de Doenças Infecciosas e Parasitárias Laboratório de Imunologia SciELO

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:43:32Z No. of bitstreams: 1 S1678-91992008000100005.pdf: 158345 bytes, checksum: 00cc19c264c88156c9a329702a886136 (MD5) Made available in DSpace on 2013-08-22T18:43:32Z (GMT). No. of bitstreams: 1 S1678-91992008000100005.pdf: 158345 bytes, checksum: 00cc19c264c88156c9a329702a886136 (MD5) Previous issue date: 2008-01-01 Made available in DSpace on 2013-09-30T19:31:13Z (GMT). No. of bitstreams: 2 S1678-91992008000100005.pdf: 158345 bytes, checksum: 00cc19c264c88156c9a329702a886136 (MD5) S1678-91992008000100005.pdf.txt: 23538 bytes, checksum: 42771519ce5923f6dcf767fadcbae3e3 (MD5) Previous issue date: 2008-01-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:08:33Z No. of bitstreams: 2 S1678-91992008000100005.pdf: 158345 bytes, checksum: 00cc19c264c88156c9a329702a886136 (MD5) S1678-91992008000100005.pdf.txt: 23538 bytes, checksum: 42771519ce5923f6dcf767fadcbae3e3 (MD5) Made available in DSpace on 2014-05-20T15:08:33Z (GMT). No. of bitstreams: 2 S1678-91992008000100005.pdf: 158345 bytes, checksum: 00cc19c264c88156c9a329702a886136 (MD5) S1678-91992008000100005.pdf.txt: 23538 bytes, checksum: 42771519ce5923f6dcf767fadcbae3e3 (MD5) Previous issue date: 2008-01-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Leptopspirosis is a syndrome with different clinical manifestations including the most severe and often fatal forms of pulmonary disease of unknown etiology. Pulmonary injury during the inflammatory process has been associated with the excessive number of alveolar macrophages (AMs) and polymorphonuclear leukocytes stimulated in the lungs and with the production of reactive oxygen and nitrogen intermediates and other inflammatory mediators. The aim of the present work was to evaluate the cellular immune response of AMs or inflammatory cells of hamsters during leptospirosis. The activity of AMs was determined by measuring nitric oxide (NO) and protein production as well as inflammatory cell infiltration in bronchoalveolar lavage (BAL) fluid. Pulmonary activity during infection was monitored by measuring pH, pressure of oxygen (PaO2), and pressure of carbon dioxide (PaCO2) in blood samples. Cellular immune response and its role in the genesis of leptospirosis have been incriminated as the main causes of tissue and pulmonary injuries, which consequently lead to the pulmonary dysfunction in severe cases of leptospirosis. The present results show a low production of NO in both supernatant of alveolar macrophage culture and BAL. In the latter, protein production was high and constant, especially during acute infection. Total and differential cell count values were 2.5X10(6) on day 4; 7.3X10(6) on day 21; and 2.3X10(6) on day 28 after infection, with lymphocytes (84.04%) predominating over neutrophils (11.88%) and monocytes (4.07%). Arterial blood gas analysis showed pulmonary compromising along with the infectious process, as observed in parameter values (mean±SD) evidenced in the infected versus control group: PaO2 (60.47mmHg±8.7 vs. 90.09mmHg±9.18), PaCO2 (57.01mmHg±7.87 vs. 47.39mmHg±4.5) and pH (7.39±0.03 vs. 6.8±1.3). Results indicated that Leptospira infection in hamsters is a good experimental model to study leptospirosis. However, some of the immune parameters showed variations which might be associated with the animal species. São Paulo State University FOA Microbiology Laboratory Federal University of São Paulo Division of Geriatric and Gerontology Inflammatory Mediators Laboratory UNESP FOA Department of Clinics, Surgery and Animal Reproduction UNIFESP Department of Parasitological and Infectious Diseases São Paulo State University FOA Microbiology Laboratory UNESP FOA Department of Clinics, Surgery and Animal Reproduction

PURPOSE: To investigate the protective effect of pentoxifylline against the lung injury observed after intestinal ischemia (I) followed by a period of reperfusion (R). METHODS: Twenty-eight male Wistar rats were equally divided into 4 experimental groups and operated under ketamine-xylazine anesthesia. (1) Sham: falsely-operated animals; (2) SS+IR: intestinal ischemia was accomplished by clipping the superior mesenteric artery during 60 minutes, with an administration of a standard volume of saline solution (SS) 5 min before the end of the ischemia period; the clip was then releases or a 120-min period of reperfusion; (3) I+PTX+R: ischemia as above, PTX was administered (25 mg/kg) and the gut reperfused as above; (4) PTX+I+PTX+R: Five minutes before arterial occlusion PTX was administered; the superior mesenteric artery was then clipped for 60 minutes. After 55-min ischemia, an additional dosis of PTX was administered; the clip was removed for reperfusion as above. At the 60th min of reperfusion a third dosis of PTX was administered. RESULTS: PTX markedly attenuated lung injury as manifested by significant decreases (all P