Melatonin can be, more effective than N-acetylcysteine, protecting acute lung injury induced by intestinal ischemia-reperfusion in rat model

OBJECTIVES: The current study compared the impact of pretreatment with melatonin and N-acetylcysteine (NAC) on the prevention of rat lung damage following intestinal ischemia-reperfusion (iIR). METHODS: Twenty-eight Wistar rats were subjected to intestinal ischemia induced by a 60 min occlusion of the superior mesenteric artery, followed by reperfusion for 120 min. Animals were divided into the following groups (n=7 per group): sham, only abdominal incision; SS+iIR, pretreated with saline solution and iIR; NAC+iIR, pretreated with NAC (20 mg/kg) and iIR; MEL+iIR, pretreated with melatonin (20 mg/kg) and iIR. Oxidative stress and inflammatory mediators were measured and histological analyses were performed in the lung tissues. RESULTS: Data showed a reduction in malondialdehyde (MDA), myeloperoxidase (MPO), and TNF-alpha in the animals pretreated with NAC or MEL when compared to those treated with SS+iIR (p<0.05). An increase in superoxide dismutase (SOD) levels in the NAC- and MEL-pretreated animals as compared to the SS+iIR group (34±8 U/g of tissue; p<0.05) was also observed. TNF-α levels were lower in the MEL+iIR group (91±5 pg/mL) than in the NAC+iIR group (101±6 pg/mL). Histological analysis demonstrated a higher lung lesion score in the SS+iIR group than in the pretreated groups. CONCLUSION: Both agents individually provided tissue protective effect against intestinal IR-induced lung injury, but melatonin was more effective in ameliorating the parameters analyzed in this study.

Effect of atenolol pre-treatment in heart damage in a model of intestinal ischemia-reperfusion

Abstract 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 factor-alpha 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.

Administracao de clonidina intravenosa e sua capacidade de reduzir a pressao da arteria pulmonar em pacientes submetidos a cirurgia cardiaca / Intravenous clonidine administration and its ability to reduce pulmonary arterial pressure in patients undergoing heart surgery / Administracion de la clonidina intravenosa y su capacidad de reducir la presion de la arteria pulmonar en pacientes sometidos a cirugia cardiaca

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), ...

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 ...

Ischemic preconditioning and the gene expression of enteric endothelial cell biology of rats submitted to intestinal ischemia and reperfusion

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.

A comparative study of pentoxifylline effects in adult and aged rats submitted to lung dysfunction by thermal injury

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<0.001). Total protein and cytokine in bronchoalveolar lavage increased in the elderly-burned group when compared to the adult-burned group (p<0.001). All parameters decreased in bolth groups treated with pentoxifylline (p<0.05). CONCLUSIONS: The injury was augmented in elderly rats when compared to adult rats. Damage was reduced with the use of pentoxifylline, however further studies are needed to evaluate the dose-response of the drug.

Pretreatment with pentoxifylline attenuates lung injury induced by intestinal ischemia/reperfusion in rats / Pré-tratamento com pentoxifilina atenua a lesão pulmonar induzida por isquemia/reperfusão intestinal em ratos

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<0.001 as compared with the SS+IR group) of pulmonary wet/dry tissue weight ratio, total protein content, myeloperoxidase activity and tumor necrosis factor-alpha. Moreover, it was apparent that in the group PTX+I+PTX+R the improvements have been even more significant. CONCLUSION: PTX exerted a protective effect on the lung from the injuries caused by intestinal ischemia/reperfusion.

OBJETIVO: Avaliar os efeitos protetores da pentoxifilina (PTX) na lesão pulmonar observada após isquemia (I) seguida de reperfusão (R) intestinal. MÉTODOS: Vinte e oito ratos machos foram divididos aleatoriamente em quatro grupos experimentais e operados sobre anestesia quetamina-xilazina. (1) Sham: animais falsamente operados; (2) SS+IR: isquemia intestinal realizada pelo clampeamento da artéria mesentérica superior durante 60 minutos, com a administração de solução salina (SS) 5 minutos antes do período de isquemia, após a retirada do clamp houve a reperfusão por mais 120 minutos; (3) I+PTX+R: isquemia como mencionado anteriormente seguida da administração de PTX (25 mg/Kg) 5 minutos antes do final da isquemia (60 minutos) seguida de reperfusão por mais 120 minutos; (4) PTX+I+PTX+R: 5 minutos antes da isquemia foi administrado PTX, após 55 minutos de isquemia foi administrado outra dose de PTX e a reperfusão mantida por mais 120 minutos, sendo que aos 60 minutos da reperfusão outra dose de PTX foi administrada. RESULTADOS: A pentoxifilina reduziu os marcadores de lesão pulmonar (proteínas totais, malondialdeído, atividade da mieloperoxidase e fator de necrose tumoral) quando comparada com o grupo não tratado (P<0.001), contudo esta redução foi mais significante no grupo PTX+I+PTX+R. CONCLUSÃO: A pentoxifilina exerce efeito protetor no pulmão no trauma causado por isquemia/reperfusão intestinal.

Ventilação mecânica de curta duração com altos níveis de O2 em pulmões de ratos idosos / Short courses of mechanical ventilation with high-O2 levels in elderly rat lungs

PURPOSE: To evaluate the effects of mechanical ventilation (MV) of high-oxygen concentration in pulmonary dysfunction in adult and elderly rats. METHODS: Twenty-eight adult (A) and elderly (E), male rats were ventilated for 1 hour (G-AV1 and G-EV1) or for 3 hours (G-AV3 and G-EV3). A and E groups received a tidal volume of 7 mL/kg, a positive end-expiratory pressure of 5 cm H2O, respiratory rate of 70 cycles per minute, and an inspiratory fraction of oxygen of 1. We evaluated total protein content and malondialdehyde in bronchoalveolar lavages (BAL) and performed lung histomorphometrical analyses. RESULTS: In G-EV1 animals, total protein in BAL was higher (33.0±1.9 µg/mL) compared with G-AV1 (23.0±2.0 µg/mL). Upon 180 minutes of MV, malondialdehyde levels increased in elderly (G-EV3) compared with adult (G-AV3) groups. Malondialdehyde and total proteins in BAL after 3 hours of MV were higher in elderly group than in adults. In G-EV3 group we observed alveolar septa dilatation and significative increase in neutrofiles number in relation to adult group at 60 and 180 minutes on MV. CONCLUSION: A higher fraction of inspired oxygen in short courses of mechanical ventilation ameliorates the parameters studied in elderly lungs.

OBJETIVO: Avaliar os efeitos da ventilação mecânica com alta concentração de oxigênio em animais adultos e idosos. MÉTODOS: Vinte e oito ratos machos (adultos e idosos; n=7 por grupo) foram divididos em ventilados por 1 hora (G-AV1 e G-EV1) e ventilados por 3 horas (G-AV3 e G-EV3). Os grupos receberam volume corrente de 7 mL/kg, pressão positive ao final da expiração de 5 cmH2O, frequência respiratória de 70 ciclos por minuto e fração inspirada de oxigênio de 100 por cento. Ao final do experimento avaliamos no lavado brônquio-alveolar as proteínas totais, malondialdeído, celularidade e a histomorfometria do parênquima pulmonar. RESULTADOS: Em animais idosos ventilados por 1 hora (G-EV1) as proteínas totais no lavado brônquio-alveolar aumentaram (33.0±1.9 µg/mL) quando comparados com os adultos (G-AV1; 23.0±2.0 µg/mL). Após 180 minutos de ventilação mecânica os níveis de malondialdeído e as proteínas totais estavam elevadas nos animais idosos (G-EV3) quando comparadas com os adultos (G-AV3; p<0.001). No grupo de animais idosos (G-EV3) observamos ainda dilatação dos septos alveolares e aumento significativo no número de neutrófilos em relação aos adultos ventilados, tanto aos 60 quanto aos 180 minutos de ventilação mecânica (p<0.001). CONCLUSÃO: A ventilação mecânica com alta fração inspirada de oxigênio por um curto período de tempo favoreceu os parâmetros pulmonares estudados nos animais idosos.

Aspectos histomorfológicos e respiratórios em modelo de lesão pulmonar aguda por sepse em ratos tratados com pentoxifilina / Histomorphologic and respiratory aspects of acute lung injury in rats induced by experimental sepsis and under pentoxifylline treatment

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.

Effects of prone and supine position on oxygenation and inflammatory mediator in a hydrochloric acid-induced lung dysfunction in rats / Efeitos da posição prona e supina na oxigenação e mediador inflamatório na disfunção pulmonar induzida por ácido clorídrico em ratos

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.

Efeitos da melatonina no sistema genital feminino: breve revisão / Melatonin effects on the female genital system: a brief review

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.

Effects of pentoxifylline on TNF-alpha and lung histopathology in HCL-induced lung injury

OBJECTIVE: To evaluate the effects of pentoxifylline on hydrochloric acid-induced lung lesions in rats subjected to mechanical ventilation. METHODS: Twenty male, adult Wistar-EPM-1 rats were anesthetized and randomly grouped (n=5 animals per group) as follows: control-MV (mechanical ventilation, MV group); bilateral instillation of HCl (HCl group); bilateral instillation of HCl followed by pentoxifylline (50 mg/kg bw) infusion (HCl+PTX group) and pentoxifylline infusion followed by bilateral instillation of HCl (PTX+HCl group). At 20, 30, 90 and 180 min after treatments, the blood partial pressures of CO2 and O2 were measured. The animals were euthanized, and bronchoalveolar lavages were taken to determine the contents of total proteins, corticosteroid and TNF-alpha. Samples of lung tissue were used for histomorphometric studies and determining the wet-to-dry (W/D) lung weight ratio. RESULTS: In the MV group, rats had alveolar septal congestion, and, in the HCl group, a remarkable recruitment of neutrophils and macrophages into the alveoli was noticed; these events were reduced in the animals with PTX+HCl. The partial pressure of oxygen increased in PTX+HCl animals (121±5 mmHg) as compared with the HCl (62±6 mmHg) and HCl+PTX (67±3 mmHg) groups within 30 minutes. TNF-alpha levels in bronchoalveolar lavage were significantly higher in the HCl group (458±50 pg/mL), reduced in the HCl+PTX group (329±45 pg/mL) and lowest in the PTX+HCl group (229±41 pg/mL). The levels of corticosteroid in bronchoalveolar lavage were significantly lower in the HCl (8±1.3 ng/mL) and HCl+PTX group (16±2 ng/mL) and were highest in the PTX+HCl (27±1.9 ng/mL). CONCLUSION: Pretreatment with PTX improves oxygenation, reduces TNF-alpha concentration and increases the concentration of corticosteroid in bronchoalveolar lavage upon lung lesion induced by HCl.

Use of the histopathology in the differential diagnosis of drowning in fresh and salty water: an experimental model establishment in rats

OBJETIVO: Desenvolver um método de diagnóstico diferencial de afogamento, pela análise quantitativa dos macrófagos alveolares, em ratos submetidos à afogamento induzido em água doce e água salgada. MÉTODOS: Foram utilizados 15 ratos adultos, machos Wistar EPM-1, pesando 360g (DP=21,3), randomizados em três grupos: G1 – controle; G2 – Água doce; G3 – Água salgada, cada um com n=5. Os animais foram anestesiados e traqueostomizados para inserção de uma cânula endotraqueal, para indução do afogamento. Os pulmões foram removidos, pesados, preparados para histologia e corados por imunohistoquímica. Os macrófagos foram contados em ambos os pulmões (direito e esquerdo) de cada animal. O teste estatístico utilizado foi o ANOVA (SPSS.10) com p<0,05.