EFFECTS OF A POTENT PEROXYNITRITE DECOMPOSITION CATALYST IN MURINE MODELS OF ENDOTOXEMIA AND SEPSIS

Excessive free-radical production due to various bacterial components released during bacterial infection has been linked to cell death and tissue injury. Peroxynitrite is a highly reactive oxidant produced by the combination of nitric oxide (NO) and superoxide anion, which has been implicated in cell death and tissue injury in various forms of critical illness. Pharmacological decomposition of peroxynitrite may represent a potential therapeutic approach in diseases associated with the overproduction of NO and superoxide. In the present study, we tested the effect of a potent peroxynitrite decomposition catalyst in murine models of endotoxemia and sepsis. Mice were injected i.p. with LPS 40 mg/kg with or without FP15 [Fe(III) tetrakis-2-(N-triethylene glycol monomethyl ether) pyridyl porphyrin] (0.1, 0.3, 1, 3, or 10 mg/kg per hour). Mice were killed 12 h later, followed by the harvesting of samples from the lung, liver, and gut for malondialdehyde and myeloperoxidase measurements. In other subsets of animals, blood samples were obtained by cardiac puncture at 1.5, 4, and 8 h after LPS administration for cytokine (TNF-alpha, IL-1 beta, and IL-10), nitrite/nitrate, alanine aminotransferase, and blood urea nitrogen measurements. Endotoxemic animals showed an increase in survival from 25% to 80% at the FP15 doses of 0.3 and 1 mg/kg per hour. The same dose of FP15 had no effect on plasma levels of nitrite/nitrate. There was a reduction in liver and lung malondialdehyde in the endotoxemic animals pretreated with FP15, as well as in hepatic myeloperoxidase and biochemical markers of liver and kidney damage (alanine aminotransferase and blood urea nitrogen). In a bacterial model of sepsis induced by cecal ligation and puncture, FP15 treatment (0.3 mg/kg per day) significantly protected against mortality. The current data support the view that peroxynitrite is a critical factor mediating liver, gut, and lung injury in endotoxemia and septic shock: its pharmacological neutralization may be of therapeutic benefit.

Effects of Lidocaine Infusion during Experimental Endotoxemia in Horses

Background The clinical efficacy of IV infusion of lidocaine for treatment of equine endotoxemia has not been studied. Hypothesis Lidocaine infusion after exposure to lipopolysaccharide (LPS) will inhibit the inflammatory response and have inhibitory effects on the hemodynamic and cytokine responses to endotoxemia. Animals Twelve horses. Methods Two equal groups (n = 6): saline (GI) and lidocaine (GII). In all animals, endotoxin (500 ng/kg body weight [BW]) was injected intraperitoneally over 5 minutes. Twenty minutes later, animals received a bolus of GI or GII (1.3 mg/kg BW) over 5 minutes, followed by a 6-hour continuous rate infusion of GI or GII (0.05 mg/kg BW/min). Treatment efficacy was judged from change in arterial blood pressure, peripheral blood and peritoneal fluid (PF) variables (total and differential cell counts, enzyme activities, and cytokine concentrations), and clinical scores (CS) for behavioral evidence of abdominal pain or discomfort during the study. Results Compared with the control group, horses treated with lidocaine had significantly lower CS and serum and PF tumor necrosis factor-alpha (TNF-alpha) activity. At several time points in both groups, total and differential cell counts, glucose, total protein and fibrinogen concentrations, and alkaline phosphatase, creatine kinase, and TNF-alpha activities were significantly different from baseline values both in peripheral blood and in PF. Conclusions and Clinical Importance Lidocaine significantly decreased severity of CS and inhibited TNF-alpha activity in PF.

Adrenalectomy enhances endotoxemia-induced hypophagia: higher activation of corticotrophin-releasing-factor and proopiomelanocortin hypothalamic neurons

Inflammatory and infectious processes evoke neuroendocrine and behavioral changes known as acute-phase response that includes activation of the hypothalamo-pituitary-adrenal (HPA) axis and reduction of food intake. Besides its action as the most important ACTH secretagogue, corticotrophin-releasing factor (CRF), synthesized in the paraventricular nucleus (PVN), is also involved in the control of food intake. Alpha-melanocyte stimulating hormone (alpha-MSH) in the arcuate nucleus also plays a role in the energy homeostasis, possessing anorexigenic effects. To investigate the participation of neuropeptides involved in the regulation of food intake during endotoxemia, we administrated lipopolysaccharide (LPS) in sham-operated and adrenalectomized (ADX) male Wistar rats to evaluate food intake, hormone responses and Fos-CRF and Fos-alpha-MSH immunoreactivity in the PVN and arcuate nucleus, as well as CRF and POW mRNA expression in these hypothalamic nuclei. In sham-operated rats, treatment with LPS (100 mu g/kg) showed lower food intake, higher plasma ACTH and corticosterone levels, as well as an increase in Fos-CRF double labeled neurons and CRF mRNA expression in the PVN, with no changes in Fos-alpha-MSH immunoreactivity and POW mRNA expression in the arcuate nucleus, compared to saline treated rats. After LPS treatment, ADX rats showed further increase in plasma ACTH levels, marked decrease of food intake, higher Fos-CRF immunoreactive neurons in the PVN and CRF mRNA expression, as well as an increase in Fos-alpha-MSH immunoreactivity and POW mRNA expression in the arcuate nucleus, compared to sham-operated rats treated with LPS. In conclusion, the present data indicate that the marked hypophagia during endotoxemia following ADX is associated with an increased activation of CRF and POW neurons in the hypothalamus and an increased mRNA expression of these neuropeptides. (C) 2008 Elsevier Inc. All rights reserved.

Inser����o de graduados em fonoaudiologia de uma universidade p��blica em programas de p��s-gradua����o

OBJETIVO: caracterizar a inser����o de egressos do Curso de Fonoaudiologia da Universidade Estadual Paulista (UNESP) - Mar��lia, em Programas de P��s-Gradua����o (PPG) Stricto Sensu brasileiros. M��TODO: foram utilizadas listas de graduados e Curriculum Vitae do egresso e do orientador. RESULTADOS: dos 537 formados, 16,57% cursaram/estavam cursando PPG e destes, 98,88% em mestrado e 37,08% tamb��m em doutorado. Na grande ��rea de conhecimento, 50% dos egressos de mestrado vincularam-se predominantemente a programas em Ci��ncias da Sa��de, 31,80% em Ci��ncias Humanas e 13,64% em Lingu��stica, Letras e Artes. No doutorado, 33, 33% em Ci��ncias Humanas, 30,30% em Ci��ncias da Sa��de e em Lingu��stica, Letras e Artes. Quanto �� ��rea de conhecimento, predominou a vincula����o, no mestrado, de 30,68% em Fonoaudiologia, 28,41% em Educa����o, 13,64% em Lingu��stica e 9,09% em Medicina I; e, no doutorado, de 33,33% em Educa����o, 30,30% em Lingu��stica e 9,09% em Fonoaudiologia; 55,68% disserta����es e 51,52% teses focalizaram a linguagem. A UNESP predominou com 39,77% no mestrado e 48,48% no doutorado. Predominou a vincula����o a Programas com conceito 4 para 52,27% dos egressos do mestrado e 45,45% do doutorado. Quando constou a informa����o (55,68%), todos receberam fomento. O Teste de Raz��o de Verossimilhan��a n��o indicou diferen��as significativas dos percentuais obtidos entre o mestrado e o doutorado. CONCLUS��O: os resultados superaram os apresentados para o mesmo Estado, mostraram a caracter��stica interdisciplinar da Ci��ncia Fonoaudiol��gica e o predom��nio de tem��tica em linguagem.

Casamento contempor��neo: revis��o de literatura acerca da op����o por n��o ter filhos

Em meio ��s diversas transforma����es sofridas pelo casamento e pela fam��lia ao longo da hist��ria, v��rias configura����es familiares convivem na contemporaneidade: nuclear, monoparental, homoparental, recomposta, entre outras possibilidades. Nesse contexto, aumenta, em v��rios pa��ses, e mais recentemente no Brasil, o n��mero de casais que escolhem n��o ter filhos. O objetivo deste trabalho foi realizar uma revis��o bibliogr��fica sobre o tema, incluindo publica����es nacionais e internacionais. A busca foi feita em bases de dados (Web of Science, PsycINFO, Medline, SciELO, Lilacs, Psicodoc, BVS-Psi, Dedalus), e foram levantados artigos completos em peri��dicos indexados e resumos de teses e disserta����es produzidas nos ��ltimos dez anos. Os resultados coletados abordam diversas facetas do fen��meno da escolha contempor��nea por n��o ter filhos: motiva����es declaradas, associa����o entre esse tipo de escolha e a situa����o profissional, rela����o com fatores de hist��ria de vida e fam��lia de origem, satisfa����o de vida e conjugal, preconceito e estere��tipos negativos.

Corporeidade e a����o nos processos de forma����o do eu

Parte-se da hip��tese de que tanto os modos de constitui����o da subjetividade, quanto as teses epistemol��gicas sobre a forma����o do eu t��m sofrido importantes mudan��as nas ��ltimas d��cadas. No plano das identidades pessoais, tal fato se expressa no atenuamento do ide��rio intimista, tradicionalmente centrado na id��ia da vida mental como espa��o privado e interior. No plano epistemol��gico, diferentes saberes v��m questionando a equival��ncia entre vida mental e interioridade psicol��gica e propondo descri����es da origem do eu que incluam a dimens��o da corporeidade e da a����o. Considerando as no����es de representa����o e de a����o como eixos fundamentais para diferentes concep����es da subjetividade, este artigo examina um modelo internalista do psiquismo, contrastando-o com outro que toma o eu como agente corporificado.

Concentra����es de vitamina A no leite humano e caracter��sticas socioecon��micas e nutricionais maternas: resultados de estudos brasileiros

OBJETIVOS: agregar e discutir os resultados de estudos realizados no Brasil que avaliaram a concentra����o de vitamina A no leite materno. FONTES DOS DADOS: foram pesquisadas as bases LILACS, Banco de Teses da Capes, SciELO (Scientific Electronic Library), e Plataforma Lattes -se����o de produ����o cient��fica. As palavras-chaves utilizadas foram: gestantes, lactante, concentra����o de vitamina A no leite humano, Brasil. As buscas foram realizadas em 2006 e atualizadas em mar��o de 2008. Foram inclu��dos todos os estudos localizados. S��NTESE DOS DADOS: foram localizados 14 estudos, publicados entre 1988 e 2008, heterog��neos quanto ao tamanho da amostra, fase do leite, per��odo do dia da coleta e m��todo de determina����o das concentra����es de vitamina A. Foram descritas concentra����es m��dias de vitamina A no leite humano entre 0,62 e 4,50 ��mol/L. CONCLUS��ES: n��o houve consenso sobre a rela����o entre concentra����o de vitamina A no leite humano e vitamina A diet��tica, estado nutricional materno, caracter��sticas obst��tricas e demogr��ficas e dura����o da gesta����o. Sugere-se que estudos futuros utilizem, amostras de leite maduro, coletadas aleatoriamente ao longo dos diferentes per��odos do dia, e a utiliza����o do high performance liquid chromatography - HPLC - como m��todo de determina����o de vitamina A.

Transtornos psiqui��tricos no p��s-parto

OBJETIVO: O p��s-parto �� um per��odo de altera����es biol��gicas, psicol��gicas e sociais. Essa �� considerada a ��poca mais vulner��vel para a ocorr��ncia de transtornos psiqui��tricos. A disforia puerperal, a depress��o p��s-parto e a psicose p��s-parto t��m sido classicamente relacionadas ao p��s-parto. Atualmente, tem sido observado que os transtornos ansiosos tamb��m est��o associados a esse per��odo. M��TODO: Neste artigo �� feita uma revis��o da bibliografia acerca de transtornos psiqui��tricos no p��s-parto a partir de artigos encontrados no PubMed e no SciELO entre os anos de 2000 e 2009. Livros, teses e outros artigos considerados relevantes citados no material consultado tamb��m foram inclu��dos. RESULTADOS: A disforia puerperal ocorre em 50% a 85% das mulheres, o quadro �� leve e transit��rio e n��o requer tratamento. A depress��o p��s-parto tem preval��ncia em torno de 13%, pode causar repercuss��es negativas na intera����o m��e-beb�� e em outros aspectos da vida da mulher e deve ser tratada. A psicose p��s-parto �� rara, aparecendo em cerca de 0,2% das pu��rperas. Tem quadro grave que envolve sintomas psic��ticos e afetivos, havendo risco de suic��dio e infantic��dio e geralmente requerendo interna����o hospitalar. Os transtornos ansiosos podem ser exacerbados ou precipitados no p��s-parto, especialmente o transtorno de ansiedade generalizada, o transtorno de estresse p��s-traum��tico e o transtorno obsessivo-compulsivo. CONCLUS��O: Apesar de n��o serem reconhecidos como entidades diagn��sticas pelos sistemas classificat��rios atuais, os transtornos mentais no puerp��rio apresentam peculiaridades cl��nicas que merecem aten����o por parte de cl��nicos e pesquisadores.

An��lise da produ����o acad��mica em vigil��ncia sanit��ria de alimentos, 1993-2007

O objetivo do estudo foi analisar os temas relacionados �� ��rea de vigil��ncia sanit��ria de alimentos abordados em pesquisas cient��ficas de cursos de p��s-gradua����o, com potencial de aplica����o no servi��o. O total de 337 teses e disserta����es apresentadas �� Universidade de S��o Paulo entre os anos de 1993 e 2007 foi analisado. Os resultados mostraram que as pesquisas desenvolvidas nas universidades t��m potencial para aplica����o em vigil��ncia sanit��ria, sobretudo no sentido de orientar os profissionais da ��rea em pr��ticas atualizadas

Resgate hist��rico do controle do tabagismo na Faculdade de Sa��de P��blica da Universidade de S��o Paulo: relato de uma experi��ncia

A a����o da Faculdade de Sa��de P��blica da Universidade de S��o Paulo na luta contra o tabagismo teve in��cio em 1975, quando a institui����o participou da III Confer��ncia Mundial de Fumo e Sa��de, realizada em New York (EUA). Depois de tr��s d��cadas de trabalho ininterrupto, ela recebeu, em 2008, da Secretaria de Estado da Sa��de de S��o Paulo, o selo prata de certifica����o de ambiente livre do tabaco. Nesse espa��o de tempo, ao lado de um trabalho educativo, realizado corpo a corpo com docentes, funcion��rios e alunos, foram realizadas pesquisas, treinamentos e desenvolvido toda uma programa����o orientada pelo Minist��rio da Sa��de / Instituto Nacional do C��ncer. Foram tamb��m produzidas in��meras monografias de mestrado, teses de doutorado e de livre doc��ncia, tendo como tema o tabagismo do ponto de vista educativo, social, m��dico e sanit��rio. Este artigo pretendeu fazer o relato dessa trajet��ria

The effect of laparoscopy access and antibiotics on the outcome of severe bacterial peritonitis in rats

Introduction: Treatment of severe bacterial peritonitis, especially by videolaparoscopy, is still a matter of investigation. The aim of the present study was to evaluate the effect of videolaparoscopy and laparotomy access with or without antibiotics on the outcome of severe bacterial peritonitis in rats. Materials and Methods: Sixty-four male Wistar rats were equally assigned to 8 groups: Sham surgery (SHAM), SHAM+antibiotics (SHAM+AB), cecal ligation and puncture (CLP), CLP+AB, CLP+videolaparoscopy (VLAP), CLP+laparotomy (LAP), VLAP+AB, and LAP+AB. All treated animals were submitted to an evaluation of bacteremia, white cell counts, and cytokine determinations: interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-alpha). The groups treated with antibiotics received gentamicin and metronidazole. Survival was monitored over a period of 7 days. Results: Peritonitis induced by CLP was severe, with IL-1, IL-6, and TNF-alpha levels and lethality being significantly higher compared to the SHAM group. The IL-6 levels in the VLAP group were significantly higher compared to the CLP and VLAP+AB groups, and the TNF-alpha levels in the VLAP and LAP+AB groups were significantly higher compared to the LAP group. The survival time was significantly higher in the CLP+AB and VLAP+AB groups, when compared to the CLP group. There was no significant difference in bacteremia and lethality rates between the resources employed for treatment of peritonitis. Conclusions: Although the use of laparoscopic access itself exacerbates the inflammatory response, the combination with antibiotics minimizes this effect and increases the survival time. However, all of the resources used for treating severe peritonitis, when applied alone or in combination, have an equivalent influence on bacteremia and lethality rates.

Hypothermia during endotoxemic shock in female mice lacking inducible nitric oxide synthase

The present study was undertaken to evaluate: (1) whether lipopolysaccharide LPS-incluced hypothermic responses may be altered during two estrous cycle phases, proestrus and diestrus, and after ovariectomy, followed by hormonal supplementation and (2) whether nitric oxide (NO) plays a role on LPS-induced hypothermia responses in female mice. Experiments were performed on adult female wild-type (WT) C57BL and inducible NO synthase knockout (KO) mice weighing 18 to 30 g. Endotoxemia was induced by intraperitoneal LIPS administration from Escherichia coli at a nonlethal dose of 10 mg/kg, and body temperature was measured by biotelemetry. Hormonal replacement was performed in ovariectomized mice through 17 beta-estradiol Silastic capsules (100 mu g) and s.c. injection of progesterone (0.5 mg per animal). We observed that during the diestrus phase, mice presented more intensive hypothermia than during proestrus phase, and hormonal supplementation with 17 beta-estradiol and progesterone attenuated hypothermia in ovariectomized mice. During diestrus and ovariectomy, KO mice had higher hypothermic response when compared with the WT group. During proestrus, the lack of statistical difference between KO and WT mice could be consequent of lower ovarian hormones plasma levels. After hormonal replacement, hypothermia was reverted in KO groups probably because of higher ovarian hormonal levels. In summary, the results demonstrated that NO release by inducible NO synthase has an important thermoregulatory role in LPS-incluced hypothermia in female mice. Besides, this involvement is directly dependent on the presence of ovarian hormones and their respective levels.

Gene expression reprogramming protects macrophage from septic-induced cell death

Sepsis induces a systemic inflammatory response leading to tissue damage and cell death. LPS tolerance affects inflammatory response. To comprehend potential new mechanisms of immune regulation in endotoxemia, we examined macrophage mRNA expression by macroarray affected by LPS tolerance. LPS tolerance was induced with subcutaneous administration of 1 mg/kg/day of LPS over 5 days. Macrophages were isolated from the spleen and the expression of 1200 genes was quantitatively analyzed by the macroarray technique. The tolerant group displayed relevant changes in the expression of 84 mRNA when compared to naive mice. A functional group of genes related to cell death regulation was identified. PARP-1, caspase 3, FASL and TRAIL genes were confirmed by RT-PCR to present lower expression in tolerant mice. In addition, reduced expression of the pro-inflammatory genes TNF-alpha and IFN-gamma in the tolerant group was demonstrated. Following this, animals were challenged with polymicrobial sepsis. Flow cytometry analysis showed reduced necrosis and apoptosis in macrophages from the tolerant group compared to the naive group. Finally, a survival study showed a significant reduction in mortality in the tolerant group. Thus, in the current study we provide evidence for the selective reprogramming of the gene expression of cell death pathways during LPS tolerance and link these changes to protection from cell death and enhanced survival rates. (C) 2010 Elsevier Ltd. All rights reserved.

Intravenous glutamine decreases lung and distal organ injury in an experimental model of abdominal sepsis

Introduction The protective effect of glutamine, as a pharmacological agent against lung injury, has been reported in experimental sepsis; however, its efficacy at improving oxygenation and lung mechanics, attenuating diaphragm and distal organ injury has to be better elucidated. In the present study, we tested the hypothesis that a single early intravenous dose of glutamine was associated not only with the improvement of lung morpho-function, but also the reduction of the inflammatory process and epithelial cell apoptosis in kidney, liver, and intestine villi. Methods Seventy-two Wistar rats were randomly assigned into four groups. Sepsis was induced by cecal ligation and puncture surgery (CLP), while a sham operated group was used as control (C). One hour after surgery, C and CLP groups were further randomized into subgroups receiving intravenous saline (1 ml, SAL) or glutamine (0.75 g/kg, Gln). At 48 hours, animals were anesthetized, and the following parameters were measured: arterial oxygenation, pulmonary mechanics, and diaphragm, lung, kidney, liver, and small intestine villi histology. At 18 and 48 hours, Cytokine-Induced Neutrophil Chemoattractant (CINC)-1, interleukin (IL)-6 and 10 were quantified in bronchoalveolar and peritoneal lavage fluids (BALF and PLF, respectively). Results CLP induced: a) deterioration of lung mechanics and gas exchange; b) ultrastructural changes of lung parenchyma and diaphragm; and c) lung and distal organ epithelial cell apoptosis. Glutamine improved survival rate, oxygenation and lung mechanics, minimized pulmonary and diaphragmatic changes, attenuating lung and distal organ epithelial cell apoptosis. Glutamine increased IL-10 in peritoneal lavage fluid at 18 hours and bronchoalveolar lavage fluid at 48 hours, but decreased CINC-1 and IL-6 in BALF and PLF only at 18 hours. Conclusions In an experimental model of abdominal sepsis, a single intravenous dose of glutamine administered after sepsis induction may modulate the inflammatory process reducing not only the risk of lung injury, but also distal organ impairment. These results suggest that intravenous glutamine may be a potentially beneficial therapy for abdominal sepsis.

Effect of PaCO(2) variation on standard base excess value in critically ill patients

Purpose: The aim of this study was to investigate the impact of acute PaCO(2) temporal variation on the standard base excess (SBE) value in critically ill patients. Methods: A total of 265 patients were prospectively observed; 158 were allocated to the modeling group, and 107 were allocated to the validation group. Two models were developed in the modeling group (one including and one excluding PaCO(2) as a variable determinant of SBE), and both were tested in the validation group. Results: In the modeling group, the mathematical model including SIDai, SIG, L-lactate, albumin, phosphate, and PaCO(2) had a predictive superiority in comparison with the model without PaCO(2) (R(2) = 0.978 and 0.916, respectively). In the validation group, the results were confirmed with significant F change statistics (R(2) change = 0.059, P < .001) between the model with and without PaCO(2). A high correlation (R = 0.99, P < .001) and agreement (bias = -0.25 mEq/L, limits of agreement 95% = -0.72 to 0.22 mEq/L) were found between the model-predicted SBE value and the SBE calculated using the Van Slyke equation. Conclusions: Acute PaCO(2), temporal variation is related to SBE changes in critically ill patients. (C) 2009 Elsevier Inc. All rights reserved.