Vitamin D3 mediates spatial memory improvement through nitric oxide mechanism in demyelinated hippocampus of rat

Abstract Studies have revealed beneficial role of vitamin D3 in neuro-cognitive function. There is also supporting evidence on the involvement of nitric oxide (NO) in the neuro-protective action. However, its over production could contribute to brain disorders. In this study, demyelination was induced by ethidium bromide (EB) injection into the right side of the hippocampus area of male rats. Vitamin D3 was administered to rats for 7 and 28 days prior to behavioral experiments using Morris water maze (MWM). Travelled distance, time spent to reach the platform, and time spent in target zone, were considered for learning and spatial memory evaluation. Nitrite oxide (NO2-) concentration was measured as an indicator for nitric oxide production. The time spent to reach the platform and the travelled distance were decreased significantly by 28 days of vitamin D3 administration (compared to 7 days experiment). Time spent in target quadrant was significantly lowered by administered vitamin on day 28. Therefore, considering a number of studies that have shown the effect of vitamin D3 on cognition, these findings could support their potential effect. Besides, nitric oxide concentration significantly differed in 28 days of vitamin D3 treated group compared with the groups treated with EB or 7 days of vitamin D3.

Chronic and acute effects of kefir: the role of angiotensin converting enzyme inhibition instead of nitric oxide balance

Probiotic consumption promotes numerous health benefits. The aim of this study is 1) to evaluate the antihypertensive effect of kefir in a hypertension rat model caused by the administration of the nitric oxide synthesis inhibitor, L-NAME, and 2) to evaluate the acute angiotensin converting enzyme (ACE) inhibitory activity of the soluble nonbacterial fraction (SNBF) of kefir. To develop the first aim, male rats were separated into three groups: control group (C) treated with 0.3 mL/100 g of milk; L-NAME group (LN) received 10 mg/kg of said inhibitor; and Kefir group (K) treated with 0.3 mL/100 g of kefir plus L-NAME (10 mg/kg of said inhibitor). The treatments were given by oral gavage twice a day for four weeks. For the second aim"instead additionally, male rats received angiotensin I (in bolus) in three doses (Ang I: 0.03, 3 and 300 µg/kg) and were separated into two groups: a) received captopril (30 mg/kg i.v.) and b)received SNBF of kefir (5 mL/kg i.v.). Blood pressure were evaluated before and after Ang I. After treatment, hemodynamic parameters were evaluated, heart weight was recorded, and body weight gain was calculated. SNBF of kefir did not decrease the blood pressure for L-NAMEtreated animals, and no changes were observed in the cardiac parameters. However, the SNBF of kefir demonstrated acute inhibition of ACE in vivo similar to that of captopril. Thus, our results suggest that kefir may improve human cardiovascular systems by using mechanisms independent of nitric oxide syntheses. Additionally, the renin angiotensin system is probably the most important system involved in kefir effect regarding hypertension.

Antioxidative Propolis From Stingless Bees (Heterotrigona Itama) Preserves Endothelium-Dependent Aortic Relaxation of Diabetic Rats: The Role of Nitric Oxide and Cyclic Guanosine Monophosphate

Propolis from stingless bees (Heterotrigona itama) is a resinous compound that exhibits antihyperglycaemia, free radical scavenging, and cardioprotective properties. The effect of propolis on diabetic vessels has not been investigated. Thus, this research aimed to determine the effect of propolis supplementation on the level of antioxidants and its mechanism of action in the aorta of diabetic rats. Male Sprague-Dawley rats were divided into five groups (n=8/group): healthy (control), untreated diabetes (DM), metformin-treated diabetes (DM+M, 300 mg/kg/day metformin), propolis-treated diabetes (DM+P, 300 mg/kg/day propolis extract) and diabetes with combined treatment (DM+M+P, dosage as former). Oral supplementation was conducted for four weeks immediately upon successful induction of diabetes by streptozotocin (60 mg/kg, intraperitoneal injection). At the end of the study, the rats were euthanised, and thoracic aorta was processed into tissue homogenates to determine the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase-1 (GPx-1) and soluble receptor for advanced glycation end-products (sRAGE). Aorta segments were harvested to examine their relaxation response towards graded concentration of acetylcholine (Ach; 10-8-10-4) M following precontraction with phenylephrine (PE; 10-6 M). Vasorelaxation towards a cumulative dose of propolis (0.01-1.00%) using PE-precontracted healthy aorta (n=6/experiments) was investigated under various simulated conditions: physiological buffer, L-NAME (10-4 M), methylene blue (10-5 M), indomethacin (10-5 M) and elevated glucose (25 mM). Propolis maintained antioxidative enzymes and sRAGE decoy molecules in the aortic tissue of the diabetic rats. The amelioration of diabetes-induced impairment of endothelium-dependent relaxation by propolis was mediated through the nitric oxide(NO)-cyclic guanosine monophosphate (cGMP) pathway. This non-clinical study reports vasoprotective property of propolis in diabetes mellitus.

Antichagásicos potenciais: síntese e modelagem molecular de híbridos de hidrazonas e liberadores de óxido nítrico / Potential antichagasic agents: synthesis and molecular modeling of hydrazones and nitric oxide releasing hybrids

A doença de Chagas é uma parasitose extremamente negligenciada, cujo agente etiológico é o protozoário Trypanosoma cruzi. Atualmente, 21 países da América Latina são considerados regiões endêmicas, onde 75-90 milhões de pessoas estão expostas à infecção, 6-7 milhões estão infectadas e mais de 41 mil novos casos surgem por ano. Entretanto, apenas os fármacos nifurtimox e benznidazol estão disponíveis no mercado. Estes, além da baixa eficácia na fase crônica da parasitose, apresentam diversos efeitos adversos, sendo que no Brasil apenas o benznidazol é utilizado. Este fato mostra a importância de se ampliar o número de fármacos disponíveis e propor quimioterapia mais eficaz para o tratamento da doença de Chagas. Como forma de contribuir para essa busca, este trabalho objetiva a síntese de compostos híbridos bioisostéricos N-acilidrazônicos e sulfonilidrazônicos, contendo grupo liberador de óxido nítrico, com potencial de interação com cisteíno-proteases parasitárias, tais como a cruzaína. Nestes derivados, os grupos liberadores de óxido nítrico utilizados foram os grupos furoxano (contendo substituinte metílico e fenílico) e éster nitrato. Propôs-se a variação de anéis aromáticos substituídos e não-substituídos, com o intuito de avaliar a possível relação estrutura-atividade (REA) desses análogos. Até o momento, somente os compostos da série N-acilidrazônica tiveram avaliação biológica realizada. Os valores de IC50 dos compostos na forma amastigota do parasita variaram entre >100 a 2,88 µM, sendo este último valor comparável ao fármaco de referência. A atividade inibitória frente à cruzaína foi de 25,2 µM a 2,2 µM. Já a liberação de óxido nítrico foi avaliada pelo método indireto de detecção de nitrato e os valores variaram entre 52,0 µM e 4.232,0 µM. Estes são bem inferiores ao composto padrão, além de não se identificar correlação direta entre a atividade biológica e a liberação de NO. Na sequência, os dois compostos mais ativos (6 e 14) foram submetidos a estudos de permeabilidade e de citotoxicidade. O composto 6 foi considerado o de maior permeabilidade segundo o Sistema de Classificação Biofarmacêutica (SCB) e todos os compostos apresentaram a taxa de fluxo menor que 2, indicando a ausência de mecanismo de efluxo. Na avaliação do potencial citotóxico desses compostos em células humanas, o derivado 6 apresentou índice de seletividade superior ao do benznidazol. Em estudos de modelagem molecular usando análise exploratória de dados (HCA e PCA), propriedades estéricas/geométricas e eletrônicas foram consideradas as mais relevantes para a atividade biológica. Além disso, estudos de docking mostraram que a posição do grupo nitro no anel aromático é importante para a interação com a cruzaína. Ademais o composto 6 não provocou mudanças significativas no ciclo celular e na fragmentação de DNA em células humanas, mostrando-se como líder promissor para futuros estudos in vivo. Atividade tripanomicida, citotoxicidade, potencial de liberação de NO e estudos de permeabilidade dos 23 derivados sulfonilidrazônicos e ésteres nitrato estão sendo avaliados

Chagas disease is an extremely neglected parasitic disease whose etiologic agent is the protozoan Trypanosoma cruzi. Currently 21 Latin American countries are considered endemic regions, where 75-90 million people are exposed to infection, 6-7 million are infected and more than 41,000 new cases occur annually. However only nifurtimox and benznidazole are available on the market. These drugs, besides low efficacy in the chronic phase of the parasite have numerous adverse effects, and in Brazil only benznidazole is used. This fact shows the importance of increasing the number of drugs available and propose more effective chemotherapy for the Chagas disease treatment. As a contribution to the problem, this study aims the synthesis of biososteric compounds from N-acylhydrazone and sulfonylhydrazone, which have the potential to interact with parasitic cysteine protease, such as cruzain, containing nitric oxide releasing groups, which also has inhibitory activity in this enzyme class. In these derivatives nitric oxide releasing groups used were furoxan (containing methyl and phenyl substituent) and nitrate ester groups. The variation of aromatic rings substituted and unsubstituted was proposed in order to evaluate the possible structure-activity relationship (SAR) of these analogs. Only N-acylhydrazone series had its biological profile evaluated up to now. The IC50 values of the compounds against the amastigote form of the parasite ranged from >100 µM to 2.88 µM, the last value being comparable to that of reference drug. Cruzain inhibitory activity ranged from 25.2 µM to 2.2 µM. The nitric oxide releasing potential was evaluated using the indirect method of detection and nitrate values ranged between 52.0 µM and 4,232.0 µM. These results are below than those of the standard compound, and there is no direct correlation between the biological activity and nitric oxide releasing potential as well. Further, the two most active compounds (6 and 14) were submitted to permeability and cytotoxicity studies. Compound 6 showed the highest permeability value according to Biopharmaceutics Classification System (BCS), and both compounds showed flow rate lower than 2, indicating no efflux mechanism. In the cytotoxicity studies of these compounds in human cells, the derivative 6 showed selectivity index greater than benznidazole. In molecular modeling studies using exploratory data analysis (HCA and PCA) steric/geometric and electronic properties were considered the most relevant for biological activity. In addition, docking studies were performed and showed that the position of the nitro group on the aromatic ring is important for the interaction with cruzain. Compound 6 did not cause significant changes in cell cycle and DNA fragmentation in human cells, showing to be a promising lead compound for future in vivo studies. Trypanocidal activity, cytotoxicity assay, NO releasing potential and permeability studies of the 23 sulfonylhydrazones and nitrate ester derivatives are being evaluated

Sudden Cardiac Arrest during Anesthesia in a 30-Month-Old Boy with Syndactyly: A Case of Genetically Proven Timothy Syndrome

Timothy syndrome, long QT syndrome type 8, is highly malignant with ventricular tachyarrhythmia. A 30-month-old boy had sudden cardiac arrest during anesthesia induction before plastic surgery for bilateral cutaneous syndactyly. After successful resuscitation, prolonged QT interval (QTc, 0.58-0.60 sec) and T-wave alternans were found in his electrocardiogram. Starting beta-blocker to prevent further tachycardia and collapse event, then there were no more arrhythmic events. The genes KCNQ1, KCNH2, KCNE1 and 2, and SCN5A were negative for long QT syndrome. The mutation p.Gly406Arg was confirmed in CACNA1C, which maintains L-type calcium channel depolarization in the heart and other systems.

Inibição da expressão de ciclooxigenase 2 em feridas cutâneas de camundongos NOD submetidos à terapia a laser de baixa intensidade / Inhibition of cyclooxygenase 2 expression in NOD mice cutaneous wound by low-level laser therapy

CONTEXTO: A terapia a laser de baixa intensidade (LLLT) tem sido relatada como importante moduladora da cicatrização de feridas cutâneas aumentando a proliferação fibroblástica associada ao aumento da expressão da citocina fator transformador de crescimento- β2 (TGF-βB2). OBJETIVO: No presente estudo foram avaliados os efeitos da LLLT sobre a expressão da enzima ciclooxigenase 2 (COX2) no sítio do reparo tecidual utilizando o modelo experimental com camundongos diabéticos não obesos (NOD) para estudar a cicatrização de feridas cutâneas. MÉTODOS: Foram utilizados 30 camundongos NOD, destes 14 ficaram diabéticos e foram divididos em dois grupos: o grupo I (n=7) foi submetido a um procedimento cirúrgico de feridas cutâneas e o grupo II (n=7) foi submetido a um procedimento cirúrgico de feridas cutâneas e tratados com LLLT. O grupo II foi submetido à LLLT nos seguintes parâmetros: 15 mW de potência, dose de 3,8 J/cm² e tempo de aplicação de 20 segundos. Após sete dias do ato cirúrgico e após aplicação do laser, os animais foram eutanasiados com sobredose de anestesia e amostras das feridas foram colhidas para posterior análise histopatológica, histomorfométrica e imuno-histoquímica. RESULTADOS: A LLLT promoveu a inibição da expressão da COX2 em feridas cutâneas de camundongos diabéticos. CONCLUSÃO: Em conjunto, os resultados sugeriram que a LLLT é capaz de modular negativamente a expressão da enzima COX2 contribuindo para o controle da resposta inflamatória em feridas cutâneas de camundongos NOD.

BACKGROUND: Low-level laser therapy (LLLT) has been reported to modulate the healing of wounds by inducing an increase in fibroblast number associated with increased expression of the cytokine transforming growth factor-β2 (TGF-β2). OBJECTIVE: In the present study, the effect of LLLT on expression of COX2 at the site of tissue repair was evaluated, using an experimental model with non obese diabetic mice (NOD) to study cutaneous wound healing. METHODS: Thirty NOD mice were used, of which 14 were diabetic and were divided into two groups: group I (n=7) underwent a surgical procedure of skin wounds and group II (n=7) underwent a surgical procedure of skin wounds and treated with LLLT. Group II was submitted to LLLT in the following parameters: 15 mW of power, dose of 3.8 J/cm² and exposure time of 20 seconds. Seven days after surgery and after laser application, animals were euthanized with an overdose of anesthesia and tissue samples were collected for subsequent histological analysis, histomorphometry and immunohistochemistry. RESULTS: The LLLT has promoted the inhibition of COX2 expression in skin wounds in mice diabetic. Taken together the results suggest that LLLT modulate the expression of COX2 improved the control of inflammatory reaction in cutaneous wound lesions in NOD mice. CONCLUSION: Taken together, the results suggested that LLLT is able to negatively modulate the expression of COX2 enzyme contributing to the inflammatory response in cutaneous wounds in NOD mice.

Role of nitric oxide in male infertility.

It has been proposed that oxidative stress plays an important role in male infertility. Many environmental, physiological and genetic factors have been implicated in poor sperm function and infertility. Although there are some definite causes for male infertility still the term “Idiopathic Infertility” remains. Various studies are going on effect of oxidative stress on fertility potential of male which can be one of the causes of idiopathic infertility. Reactive oxygen species (ROS) are highly reactive oxidizing agent belonging to class of free radicals. Excessive generation of ROS in semen by leukocytes as well as by abnormal spermatozoa could be a cause of infertility because it leads to injury to spermatozoa.Nitric oxide (NO) is one of the reactive oxygen species that has been implicated in variety of physiologic cell signaling mechanisms in many tissues and is recognized as a molecule that importantly regulates the biology and physiology of reproductive function.The clinical significance of seminal oxidative stress is suggested by several independent studies indicating a link between peroxidative damage to human spermatozoa and the incidence of male infertility.

Non-asthmatic patients show increased exhaled nitric oxide concentrations

OBJECTIVE: Evaluate whether exhaled nitric oxide may serve as a marker of intraoperative bronchospasm. INTRODUCTION: Intraoperative bronchospasm remains a challenging event during anesthesia. Previous studies in asthmatic patients suggest that exhaled nitric oxide may represent a noninvasive measure of airway inflammation. METHODS: A total of 146,358 anesthesia information forms, which were received during the period from 1999 to 2004, were reviewed. Bronchospasm was registered on 863 forms. From those, three groups were identified: 9 non-asthmatic patients (Bronchospasm group), 12 asthmatics (Asthma group) and 10 subjects with no previous airway disease or symptoms (Control group). All subjects were submitted to exhaled nitric oxide measurements (parts/billion), spirometry and the induced sputum test. The data was compared by ANOVA followed by the Tukey test and Kruskal-Wallis followed by Dunn's test. RESULTS: The normal lung function test results for the Bronchospasm group were different from those of the asthma group (p <0.05). The median percentage of eosinophils in induced sputum was higher for the Asthma [2.46 (0.45-6.83)] compared with either the Bronchospasm [0.55 (0-1.26)] or the Control group [0.0 (0)] (p <0.05); exhaled nitric oxide followed a similar pattern for the Asthma [81.55 (57.6-86.85)], Bronchospasm [46.2 (42.0 -62.6] and Control group [18.7 (16.0-24.7)] (p< 0.05). CONCLUSIONS: Non-asthmatic patients with intraoperative bronchospasm detected during anesthesia and endotracheal intubation showed increased expired nitric oxide.

Concentração de nitrito endometrial e a ocorrência de patologias uterinas em vacas / Endometrial nitrite concentration and the occurrence of uterine pathologies of cows

Relacionou-se a concentração de nitrito com a ocorrência de enfermidades uterinas. Lavado intrauterino de 1ml de PBS foi realizado em 25 peças uterinas de vacas vazias para mensuração da concentração de nitrito pela reação de Griess. Elevada concentração de nitrito exibiu relação significativa com distrofia angiomatosa (157,57±108,80mM), endometrite (102,96±87,58mM) e fibrose periglandular (99,15±89,75mM); e não significativa com e hiperplasida endometrial cística (94,07±18,89mM) e adenomiose (77,40±81,25mM). Contudo, elevada concentração de nitrito mostrou relação significativa com adenomiose acentuada profunda pelo teste t. Os resultados indicam que a síntese de óxido nítrico está elevada nessas enfermidades.

The occurrence of uterine pathologies was evaluated considering uterine nitrite concentration. The uterus of 25 non pregnant cows was washed with 1ml of PBS to measure the nitrite concentration using the Griess reaction . There was significant relationship between high nitrite concentration with angiomatosis dystrophy (157,57 ±108,80mM), endometritis (102,96±87,58mM) and periglandular fibrosis (99,15±89,75mM). No relation was found between nitrite concentration and cystic endometrial hyperplasia (94,07±18,89mM) and adenomyosis (77,40±81,25mM). However, high nitrite concentration showed a significant relationship with deep accentuate adenomyosis by t test. The data suggest that nitric oxide synthesis is elevated in these illnesses.

Influência do óxido nítrico na cicatrização da esofagite erosiva em fumantes / Influence of nitric oxide in healing of erosive oesophagitis in smokers

INTRODUÇÃO: O cigarro é citado como um possível fator externo que influencia sobre a fisiopatologia e a evolução da doença do refluxo gastroesofágico (DRGE). O cigarro contém uma quantidade significativa de óxido nítrico (NO). Os objetivos deste trabalho foram avaliar, em pacientes fumantes com DRGE erosiva, o papel do NO, pela análise de seus precursores: nitratos salivar (SNO3) e gástrico (GNO3) e nitrito salivar (SNO2), nos resultados de cicatrização após tratamento clínico, bem como comparar esta cicatrização com não-fumantes. MATERIAIS E MÉTODOS: 31 pacientes (grupo GF) adultos fumantes, com sintomas típicos de DRGE e endoscopia digestiva alta (EDA) mostrando esofagite A ou B de Los Angeles e 10 adultos não-fumantes, com mesmas características de DRGE em sintomas e EDA (grupo GNF) realizaram manometria esofágica, pHmetria de 24 horas, dosagens de bicarbonato salivar, dosagens de SNO3, GNO3 e SNO2. Foram tratados com pantoprazol 40 mg/dia por oito semanas e repetiram a EDA. Comparou-se os grupos GF e GNF e também os grupos que cicatrizaram (grupo GC=18 pacientes) e não cicatrizaram (grupo GNC=23 pacientes). RESULTADOS E DISCUSSÃO: A cicatrização da esofagite erosiva ocorreu em dez pacientes (32,2%) em GF e oito pacientes (80%) em GNF (p<0,05). A manometria esofágica não mostrou diferenças estatísticas na avaliação do esfíncter inferior do esôfago (EIE) entre GF e GNF (p=0,517). A pHmetria de 24 horas mostrou maior intensidade de refluxo ácido em fumantes, com diferença estatisticamente significativa entre GF e GNF (p<0,05), com médias em GF: escore de DeMeester: 35,26, porcentagem de tempo com pH<4: 8,67 e tempo total com pH <4: 120,42 no GF, e médias no GNF: escore de DeMeester: 12,53, porcentagem de tempo com pH<4: 2,97 e tempo total com pH <4: 2,97. Bicarbonato salivar médio foi 4,54 uM/L em GF e 2,90 uM/L em GNF (p<0,05), portanto fumantes têm maior depuração esofágica. SNO2 média foi...

INTRODUCTION: Cigarettes are one of the possible external factors to influence the physiopathology and the evolution of the gastroesophageal reflux disease (GERD). Cigarettes contain a significant amount of nitric oxide (NO). The objectives of this work were, in smokers with erosive esophagitis, to evaluate the role of the nitric oxide (NO), carrying out an assessment of its precursors: salivary nitate (SNO3), gastric nitrate (GNO3) and salivary nitrite (SNO2), in the healing after clinical treatment, as well as to compare healing between smokers and non-smokers. MATERIALS AND METHODS: 31 adults smokers (group GS), who had typical GERD symptoms and an upper endoscopy which showed Los Angeles grade A or B esophagitis and ten non-smoker adults patients, with the same GERD symptoms and with similar esophagitis (group GNS), were submitted to esophageal manometry, 24-hour pHmetry, salivary bicarbonate count, and counts of SNO3, GNO3 and SNO2. Then they were treated with pantoprazole 40 mg/day for eight weeks and repeated upper endoscopy. We compared the groups GS and GNS, and the group where healing was observed (group GH=18 patients) with the group with no healing (GNH=23 patients). RESULTS/ DISCUSSION: Erosive esophagitis healing occured in ten patients (32.2%) of the GS and eight patients (80%) of the GNS (p <0.05). Esophageal manometry didn't show significantly statistical differences in the evaluation of the lower esophageal sphincter (LES), between GS and GNS (p=0.517). 24-hour pHmetry showed a more intense reflux in smokers, with significantly statistical differences between GS and GNS (p <0.05) in DeMeester score averages of: 35.26, percent of time with pH <4: 8.67 and total time with pH <4: 120.42 in GS, and DeMeester score averages of: 12.53, percent of time with pH <4: 2.97 and total time with pH <4: 2.97 in GNS. Mean salivary bicarbonate was 4.54 uM/L in GS and 2.90 uM/L in GNS (p <0.05), so smokers have more...

Óxido nítrico inalatório para crianças com síndrome do desconforto respiratório agudo: [revisão] / Inhaled nitric oxide for children with acute respiratory distress syndrome: [review]

JUSTIFICATIVA E OBJETIVOS: O objetivo desse estudo foi rever a literatura sobre a utilização de óxido nítrico inalatório em crianças com síndrome do desconforto respiratório agudo. CONTEÚDO: Revisão bibliográfica e seleção de publicações mais relevantes sobre óxido nítrico inalatório, utilizando a base de dados MedLine e Cochrane de Revisões Sistemáticas. A revisão incluiu descrição de aspectos da definição, fisiopatologia e tratamento ventilatório da síndrome do desconforto respiratório agudo, assim como o metabolismo, efeitos biológicos e aplicação clínica do óxido nítrico inalatório, comentando dose, administração e retirada do gás, precações, efeitos adversos e contra-indicações. CONCLUSÕES: O óxido nítrico, vasodilatador pulmonar seletivo, tem efeitos benéficos sobre as trocas gasosas e ventilação em crianças com hipóxia grave. É seguro quando administrado em ambiente de tratamento intensivo sob rigorosa monitorização. Estudos aleatórios e controlados devem enfocar a administração precoce do gás na síndrome do desconforto respiratório agudo, quando essa é potencialmente reversível.

BACKGROUND AND OBJECTIVE: The objective of this study was to review the literature on inhaled nitric oxide to children with acute respiratory distress syndrome. CONTENTS: A review of literature and selection of the most important publications on inhaled nitric oxide, using the MedLine and Cochrane Systematic Review Databases. This review was organized as follows: introduction; metabolism and biological effects; clinical applications; dosage, gas administration and weaning process; warnings and side-effects. Inhaled nitric oxide use was described in acute respiratory distress syndrome. CONCLUSIONS: Inhaled nitric oxide as the first vasodilator to produce selective pulmonary vasodilation has beneficial effects on gas exchange and ventilation, improving outcome in children with severe hypoxia. It is safe when administered in intensive care units under strict surveillance and monitoring. Further studies should be concentrated on early treatment, when acute respiratory distress syndrome is potentially reversible.

Efeitos do óxido nítrico inalatório na hipertensão pulmonar de pacientes após cirurgia valvar mitral / Effects of inhaled nitric oxide on pulmonary hypertension in patients after mitral valve surgery

OBJETIVO: O estudo consiste em verificar os efeitos da utilização do óxido nítrico inalatório (NOi) em pacientes no pós-operatório de cirurgia valvar mitral. MÉTODO: Os efeitos do NOi foram medidos principalmente por meio da verificação de alterações na pressão arterial pulmonar (PAP). Outras medidas realizadas incluíram: pressão arterial média (PAM), pressão venosa central média (PVC), pressão média de átrio esquerdo (PAE), saturação de oxigênio por oximetria de pulso, complacência pulmonar estática e gradiente transpulmonar (GTP). RESULTADOS: Nos 20 pacientes estudados, obteve-se tempo mediano de utilização do NOi de 19,1 horas. A PAP média reduziu significativamente de 33,8 ± 6,17 mmHg (pré-NOi) para 29,1 ± 6,46 mmHg, nos 30 minutos iniciais e para 28,4 ± 5,22 mmHg, considerando a média de todas as medidas pós-NOi (p< 0,05). O GTP também apresentou redução estatisticamente significativa. Não houve alterações significativas nas demais medidas hemodinâmicas. CONCLUSÃO: Os achados indicam que a utilização do NOi reduz a PAP sem efeitos sistêmicos, demonstrando efeito vasodilatador seletivo no sistema vascular pulmonar.

OBJECTIVE: Cardiac surgery in patients with pulmonary hypertension may present severe postoperative complications. The study consists of verifying the effects of using inhaled nitric oxide (iNO) in patients during the postoperative period of mitral valve surgery. METHODS: The effects of iNO were measured mainly by verifying changes in pulmonary artery pressure (PAP). Other measures performed included mean arterial pressure (MAP), mean central venous pressure (CVP), mean left atrial pressure (LAP), oxygen saturation by pulse oxymetry, and static pulmonary compliance. RESULTS: In the 20 patients studied, a median time of iNO use of 19.1 hours was obtained. The mean PAP was significantly reduced from 33.8 ± 6.17 mmHg (pre-iNO) to 29.1 ± 6.46 mmHg in the initial 30 minutes and to 28.4 ± 5.22 mmHg considering the mean of all post-iNO measures (p< 0.05). No significant changes occurred in the other hemodynamic measures. CONCLUSION: The findings indicate that the use of iNO, in post-operative period of mitral valve operation associated with pulmonary hypertension, reduces PAP without systemic effects, demonstrating a selective vasodilator effect on the pulmonary vascular system.

Hipertensão pulmonar: diagnóstico invasivo pelo cateterismo / Pulmonary hypertension: invasive diagnosis by cardiac catheterization

Apesar de o diagnóstico da hipertensão arterial pulmonar poder ser realizado eficazmente de forma não-invasiva, o cateterismo cardíaco é geralmente necessário nos pacientes com essa condição, a fim de avaliar precisamente os níveis pressóricos nas câmaras direitas e na artéria pulmonar e de medir o débito cardíaco e a resistência vascular tanto pulmonar como sistêmica. Além disso, o teste é realizado com vasodilatador pulmonar, de preferência o óxido nítrico, para se estimar o grau de reatividade da vasculatura pulmonar. Essa avaliação invasiva pelo cateterismo tem importantes implicações prognósticas e terapêuticas no seguimento desses pacientes. Neste artigo são revistos as indicações, o médico e a interpretação dos resultados do estudo hemodinâmico nos pacientes portadores de hipertensão arterial pulmonar idiopática.

Do we need to use nitric oxide in preterm babies in developing countries?

Neonatal care in developing nations is advancing rapidly. There is an increasing tendency to include nitric oxide in the therapeutic armamentarium. But the opinion regarding its use remains divided among neonatologists even in the western world. Nitric oxide has an established role in the management of persistent pulmonary hypertension in term neonates. However, the use of nitric oxide in preterm neonates has been controversial and the Cochrane review updated in 2001 did not give conclusive answers. There have been adequately powered multi-centre trials recently on the issue, planned to resolve the controversy. The present communication highlights the salient features and conclusions drawn from these trials.

Papel da indução de tolerância oral no remodelamento de vias aéreas e na expressão da óxido nítrico sintase neuronal / Role of oral tolerance induction in airway remodeling and the expression of neuronal nitric oxide syntase

Foram investigados os efeitos de dois modelos de indução de tolerância oral em cobaias com inflamação crônica alérgica pulmonar. A indução de tolerância oral concomitante ao início da sensibilização ou depois de estabelecida a resposta alérgica atenuou a inflamação eosinofílica, os títulos de IgG1 e o remodelamento brônquico. A redução dos linfomononucleares e da hiperresponsividade brônquica foi mais efetiva quando a indução de tolerância foi feita em animais previamente sensibilizados. Houve dissociação entre controle da inflamação eosinofílica e a produção de óxido nítrico exalado, o que sugere um mecanismo novo ativado pela indução de tolerância oral...

The effects of two models of oral tolerance induction were investigated in guinea pigs with allergic pulmonary chronic inflammation. The induction of oral tolerance concomitant with the beginning of sensitization or after the established the allergic response attenuated the eosinophilic inflammation, the IgG1 titles and the airway remodeling. The reduction of lymphomononuclear and bronchial hyperresponsiveness were more effective when the induction of tolerance was made in animals previously sensitized. There was dissociation between the control of the eosinophilic inflammation and the exhaled nitric oxide production, what suggests a new mechanism activated by the induction of oral tolerance...

Comparison of nitric oxide concentration in seminal fluid between infertile patients with and without varicocele and normal fertile men

Elevated nitric oxide [NO] levels have been shown to have toxic effects on sperm function and motility. This study was conducted to compare NO levels in the seminal fluid of infertile men with varicocele with those of infertile and fertile men without varicocele. Semen samples were obtained from 40 infertile men with varicocele [group 1], 40 infertile men without varicocele [group 2], and 40 fertile volunteers without varicocele [group 3]. NO levels in the seminal plasma of patients in each group were measured and compared. In infertile men with varicocele, semen parameters, including sperm count and motility, and grade of varicocele were also determined. Mean NO concentrations were 52.34 +/- 26.62 micro mol/L, 37.06 +/- 20.39 micro mol/L, and 33.7 +/- 18.99 micro mol/L in groups 1, 2, 3, respectively. Concentrations in group 1 were significantly higher than those in groups 2 and 3 [P=0.001]. In group 1, no significant correlations were seen between NO concentrations and grades of varicocele, sperm count, sperm motility, or ages of the patients. Data from the current study suggest a possible role of NO in damaging the sperm function in varicocele as demonstrated by an increased concentration of NO in the seminal fluid of infertile men with varicocele compared with the seminal fluid of fertile and infertile men without varicocele