Protective effect of combined melatonin and alpha-tocopherol administration in spinal cord ischemia-reperfusion injury in rat / Efecto protector de la administración combinada de melatonina y alfa-tocoferol en la lesión por isquemia-reperfusión de la médula espinal en ratas

Oxidative stress and inflammation are the key players in the development of motor dysfunction post-spinal cord ischemic reperfusion injury (SC-IRI). This study investigated the protective effect of concomitant pre-administration of melatonin and alpha-tocopherol on the early complications (after 48 hours) of spinal cord IRI injury in rats. Melatonin or α-tocopherol were preadministered either individually or in combination for 2 weeks, then rats were exposed SC-IRI. Neurological examinations of the hind limbs and various biochemical markers of oxidative stress and inflammation in the SC tissue were assessed. Solely pre-administration of either melanin or α-tocopherol significantly but partially improved motor and sensory function of the hind limbs mediated by partial decreases in SC levels of MDA, AOPP and PGE2 levels and activities of SOD, partial significant decreases in plasma levels of total nitrate/nitrite and significant increases in AC activity of GSH-Px. However, combination therapy of both drugs resulted in the maximum improvements in all neurological assessments tested and biochemical endpoints. In conclusion, by their synergistic antioxidant and antiinflammatory actions, the combination therapy of melatonin and α-tocopherol alleviates SC-IRI induced paraplegia.

El estrés oxidativo y la inflamación son claves en el desarrollo de la disfunción motora posterior a lesión isquémica de la médula espinal (SC-IRI). Este estudio investigó acerca del efecto protector de la administración previa concomitante de la melatonina y alfa-tocoferol en las complicaciones tempranas (después de 48 horas) de la lesión de IRI de la médula espinal en ratas. La melatonina o el α-tocoferol se administraron individualmente o en combinación durante 2 semanas, luego las ratas fueron expuestas a SC-IRI. Se evaluaron los exámenes neurológicos de las miembros pélvicos y diversos marcadores bioquímicos de estrés oxidativo e inflamación en el tejido subcutáneo. Solo la administración previa de melatonina o α-tocoferol mejoró parcial y significativamente la función motora y sensorial de los miembros pélvicos mediadas por disminuciones parciales en los niveles de SC de los niveles de MDA, AOPP y PGE2 y las actividades de la SOD, disminuciones significativas parciales en los niveles plasmáticos del total nitrato / nitrito y aumentos significativos en la actividad de AC de GSH-Px. Sin embargo, se observaron los mejores resultados durante la combinación de ambos fármacos en todas las evaluaciones neurológicas y en los puntos finales bioquímicos. En conclusión, debido a sus acciones antioxidantes y antiinflamatorias sinérgicas, la terapia de melatonina y α-tocoferol alivia la paraplejía inducida por SC-IRI.

Acute but not chronic metabolic acidosis potentiates the acetylcholine-induced reduction in blood pressure: an endothelium-dependent effect

Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control.

Oxidant-antioxidant status in Egyptian children with sickle cell anemia: a single center based study / Estado oxidante-antioxidante em crianças egípcias com anemia falciforme: estudo baseado em um único centro

OBJECTIVE: the present study was conducted to investigate the oxidant-antioxidant status in Egyptian children with sickle cell anemia. METHODS: the serum levels of total antioxidant capacity (TAO), paraoxonase (PON), vitamin E, nitrite, and malondialdehyde (MDA) were measured in 40 steady state children with homozygous sickle cell anemia (24 males and 16 females) and 20 apparently healthy age- and gender-matched controls. RESULTS: mean serum TAO, PON, vitamin E, and nitrite levels were significantly lower in the group with sickle cell anemia, whereas mean serum MDA was significantly higher in these children compared to controls. No significant differences in mean levels of TAO, PON, nitrite, vitamin E, and MDA were found in sickle cell anemia patients receiving hydroxyurea when compared with those not receiving hydroxyurea. A significant negative correlation between serum nitrite and the occurrence of vaso-occlusive crises (VOC) was observed (r = -0.3, p = 0.04). PON level was found to be positively correlated with patients' weight and BMI (r = -0.4, p = 0.01; r = -0.7, p < 0.001, respectively), but not with frequency of VOC. The area under the curve of serum nitrite in predicting occurrence of VOC was 0.782, versus 0.701 for PON, and 0.650 for TAO (p = 0.006). Serum MDA was not correlated with nitrite, PON, TAO, or vitamin E levels. No significant correlations were detected between serum nitrite and hemoglobin or antioxidant enzymes. CONCLUSION: children with sickle cell anemia have chronic oxidative stress that may result in increased VOC, and decreased serum nitrite may be associated with increases in VOC frequency. A novel finding in this study is the decrease in PON level in these patients, which is an interesting subject for further research. .

OBJETIVO: o presente estudo foi realizado com o objetivo de investigar o estado oxidante-antioxidante em crianc¸as egípcias com anemia falciforme. MÉTODOS: dosamos os níveis séricos da capacidade antioxidante total (CAT), paraoxonase (PON), vitamina E, nitrito e malondialdeído (MDA) em 40 crianças estáveis com anemia falciforme homozigótica (24 meninos e 16 meninas), e 20 controles pareados por idade/sexo aparente-mente saudáveis. RESULTADOS: os níveis séricos médios da CAT, PON, vitamina E e nitrito foram significativamente menores, ao passo que o nível sérico médio de MDA foi significativamente maior em crianças com anemia falciforme (AF), em comparação aos controles. Não foram encontradasdiferenças significativas nos níveis médios de CAT, PON, nitrito, vitamina E e MDA em pacientescom AF em tratamento com hidroxiureia, em comparação aos que receberam hidroxiureia. Encontramos uma correlação negativa significativa entre o nitrito sérico e a ocorrência decrises vaso-oclusivas agudas (CVO) (r = -0,3, p = 0,04). Descobrimos que o nível de PON está correlacionado positivamente com o peso e o IMC dos pacientes (r = -0,4; p = 0,01; r = -0,7; p < 0,001, respectivamente), porém não com a frequência de CVO. A área sob a curva (ASC) donitrito sérico na previsão da ocorrência de CVO foi 0,782, em comparação a 0,701 para PON e 0,650 para CAT (p = 0,006). O MDA não está correlacionado a nitrito, PON, CAT ou vitamina E. Não foram detectadas correlações significativas entre nitrito sérico e hemoglobina ou enzimas antioxidantes. CONCLUSÃO: crianças com AF apresentam estresse oxidativo crônico que pode resultar emaumento das CVO. Em crianças com AF, a redução nos níveis de ...

EXHALED AND PLASMA NITRITE: a comparative study among healthy, cirrhotic and liver transplant patients / Nitrito exalado e plasmático: um estudo comparativo entre pacientes transplantados saudáveis, cirrose e fígado

Context There is a relative lack of studies about exhaled nitrite (NO2-) concentrations in cirrhotic and transplanted patients. Objective Verify possible differences and correlations between the levels of NO2-, measured in plasma and exhaled breath condensate collected from patients with cirrhosis and liver transplant. Method Sixty adult male patients, aged between 27 and 67 years, were subdivided into three groups: a control group comprised of 15 healthy volunteers, a cirrhosis group composed of 15 volunteers, and a transplant group comprised of 30 volunteers. The NO2- concentrations were measured by chemiluminescence. Results 1) The analysis of plasma NO2- held among the three groups showed no statistical significance. 2) The comparison between cirrhotic and control groups, control and transplanted and cirrhotic and transplanted was not statistically significant. 3) The measurements performed on of NO2- exhaled breath condensate among the three groups showed no statistical difference. 4) When comparing the control group samples and cirrhotic, control and transplanted and cirrhotic and transplanted, there was no significant changes in the concentrations of NO2-. Conclusion No correlations were found between plasma and exhaled NO2-, suggesting that the exhaled NO2- is more reflective of local respiratory NO release than the systemic circulation. .

Contexto Observa-se relativa falta de estudos sobre nitrito (NO2-) exalado como biomarcador de lesão, após transplante de fígado. Objetivo Verificar possíveis diferenças e correlações entre os níveis de nitrito (NO2-), medido no plasma e condensado do exalado pulmonar de pacientes com cirrose e transplante de fígado. Método Sessenta pacientes adultos, masculinos, idades entre 27 e 67 anos, foram divididos em três grupos: grupo controle composto por 15 voluntários saudáveis, grupo cirrose, composto por 15 voluntários e, grupo de transplante, composto por 30 voluntários. As dosagens plasmáticas e do condensado do exalado pulmonar foram realizadas por quimioluminescência. Resultados A análise os valores de NO2- plasmático não mostrou diferença entre os grupos. As comparações entre grupos cirrose e controle, controle e transplantados e cirrose e transplante não foram significativas. As medidas em amostras de condensado do exalado pulmonar entre os três grupos não evidenciaram diferenças estatísticas. Ao comparar as amostras dos grupos controle e cirrótico, controle e transplantado e cirróticos e transplantados, não houve alterações significativas nas concentrações de NO2-. Conclusão Não foram encontradas correlações entre plasma e condensado do exalado pulmonar, sugerindo que o NO exalado reflete mais as condições respiratórias locais de liberação de NO do que a circulação sistêmica. .

Estresse Isolado ou Associado ao Etanol Libera Prostanóides em Aorta de Ratos via ?2-Adrenoceptores / Stress Alone or associated with Ethanol Induces Prostanoid Release in Rat Aorta via ?2-Adrenoceptor

Fundamento: Estresse e etanol são ambos, independentemente, importantes fatores de risco cardiovascular. Objetivo: avaliar o risco cardiovascular do consumo de etanol e exposição ao estresse, isolados e em associação, em ratos machos adultos. Métodos: Os ratos foram separados em quatro grupos: controle, etanol (20% na água de beber durante seis semanas), estresse (imobilização 1h dia/5 dias por semana/ 6 semanas) e estresse/etanol. As curvas de concentração-resposta à noradrenalina - na ausência e na presença de ioimbina, L-NAME ou indometacina - ou fenilefrina foram determinadas em aortas torácicas com e sem endotélio. EC50 e resposta máxima (n = 8-12) foram comparadas através de ANOVA de dois fatores (two-way) / método de Bonferroni. Resultados: Estresse ou estresse em associação com o consumo de etanol aumentaram as respostas máximas de noradrenalina em aortas intactas. Essa hiper-reatividade foi eliminada pela remoção do endotélio, ou pela presença da indometacina ou ioimbina, mas não foi alterada pela presença de L-NAME. Enquanto isso, o consumo de etanol não alterou a reatividade à noradrenalina. As respostas da fenilefrina em aortas com e sem endotélio também permaneceram inalteradas independentemente do protocolo. Conclusão: O estresse crônico aumentou as respostas aórticas dos ratos à noradrenalina. Esse efeito é dependente do endotélio vascular e envolve a liberação de prostanóides vasoconstritores através da estimulação de α-2 adrenoceptores endoteliais. Além disso, o consumo crônico de etanol pareceu não influenciar as respostas de noradrenalina em aorta de rato, nem modificar o aumento de tais respostas observadas em consequência da exposição ao estresse. .

Background: Stress and ethanol are both, independently, important cardiovascular risk factors. Objective: To evaluate the cardiovascular risk of ethanol consumption and stress exposure, isolated and in association, in male adult rats. Methods: Rats were separated into 4 groups: Control, ethanol (20% in drinking water for 6 weeks), stress (immobilization 1h day/5 days a week for 6 weeks) and stress/ethanol. Concentration-responses curves to noradrenaline - in the absence and presence of yohimbine, L-NAME or indomethacin - or to phenylephrine were determined in thoracic aortas with and without endothelium. EC50 and maximum response (n=8-12) were compared using two-way ANOVA/Bonferroni method. Results: Either stress or stress in association with ethanol consumption increased the noradrenaline maximum responses in intact aortas. This hyper-reactivity was eliminated by endothelium removal or by the presence of either indomethacin or yohimbine, but was not altered by the presence of L-NAME. Meanwhile, ethanol consumption did not alter the reactivity to noradrenaline. The phenylephrine responses in aortas both with and without endothelium also remained unaffected regardless of protocol. Conclusion: Chronic stress increased rat aortic responses to noradrenaline. This effect is dependent upon the vascular endothelium and involves the release of vasoconstrictor prostanoids via stimulation of endothelial alpha-2 adrenoceptors. Moreover, chronic ethanol consumption appeared to neither influence noradrenaline responses in rat thoracic aorta, nor did it modify the increase of such responses observed as a consequence of stress exposure. .

Prevalência de dislipidemia em adultos de meia-idade com polimorfismo do gene NOS3 e baixa aptidão cardiorrespiratória / Prevalence of dyslipidemia in middle-aged adults with NOS3 gene polymorphism and low cardiorespiratory fitness

OBJETIVO: Analisar a influência da associação dos polimorfismos do gene da sintase do óxido nítrico endotelial (NOS3) para as posições -786T>C, Glu298Asp e íntron 4b/a e a aptidão cardiorrespiratória sobre as concentrações de nitrito/nitrato, pressão arterial, perfil lipídico e prevalência de doenças cardiometabólicas em adultos. SUJEITOS E MÉTODOS: Noventa e duas pessoas foram divididas de acordo com o genótipo: não polimórficas (NP) e polimórficas (P). Posteriormente, foram subdivididas pela aptidão cardiorrespiratória associada ao genótipo: alta (ANP e AP) ou baixa (BNP e BP). RESULTADOS: Os indivíduos que apresentavam polimorfismo para as posições Glu298Asp+Íntron 4b/a e Glu298Asp+-786T>C e baixa aptidão cardiorrespiratória apresentaram maiores valores de colesterol total e maior prevalência de dislipidemia. CONCLUSÃO: Nossos dados demonstram que os polimorfismos do gene da NOS3 para essas duas associações influenciam os níveis de colesterol plasmático, e essa associação foi mais claramente observada quando os indivíduos apresentavam menor nível de aptidão cardiorrespiratória.

OBJECTIVE: To evaluate the influence of the interaction between endothelial nitric oxide synthase gene (NOS3) polymorphisms at positions -786T>C, Glu298Asp and intron 4b/a, and cardiorespiratory fitness on plasma nitrite/nitrate levels, blood pressure, lipid profile, and prevalence of cardiometabolic disorders. SUBJECTS AND METHODS: Ninety-two volunteers were genotyped for NOS3 polymorphisms at positions (-786T>C and Glu298Asp) and (intron 4b/a) and divided according to the genotype: non-polymorphic (NP) and polymorphic (P). After that, they were subdivided according to the cardiorespiratory fitness associated with genotype: high (HNP and HP) and low (LNP and LP). RESULTS: The subjects with polymorphism for the interactions at positions Glu298Asp + intron 4b/a, and Glu298Asp+-786T>C showed the highest values in total cholesterol, as well as dyslipidemia. CONCLUSION: Our findings show that NOS3 gene polymorphisms at positions -786T>C, Glu298Asp, and intron 4b/a exert negative effects on the lipid profile compared with those who do not carry polymorphisms.

Oxidative stress is associated with the number of components of metabolic syndrome: LIPGENE study

Previous evidence supports the important role that oxidative stress (OxS) plays in metabolic syndrome (MetS)-related manifestations. We determined the relationship between the number of MetS components and the degree of OxS in MetS patients. In this comparative cross-sectional study from the LIPGENE cohort, a total of 91 MetS patients (43 men and 48 women; aged between 45 and 68 years) were divided into four groups based on the number of MetS components: subjects with 2, 3, 4 and 5 MetS components (n=20, 31, 28 and 12, respectively). We measured ischemic reactive hyperemia (IRH), plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), total nitrite, lipid peroxidation products (LPO), hydrogen peroxide (H2O2), superoxide dismutase (SOD) and glutathione peroxidase (GPx) plasma activities. sVCAM-1, H2O2 and LPO levels were lower in subjects with 2 or 3 MetS components than subjects with 4 or 5 MetS components. IRH and total nitrite levels were higher in subjects with 2 or 3 MetS components than subjects with 4 or 5 MetS components. SOD and GPx activities were lower in subjects with 2 MetS components than subjects with 4 or 5 MetS components. Waist circumference, weight, age, homeostatic model assessment-beta, triglycerides (TGs), high-density lipoprotein and sVCAM-1 levels were significantly correlated with SOD activity. MetS subjects with more MetS components may have a higher OxS level. Furthermore, association between SOD activity and MetS components may indicate that this variable could be the most relevant OxS biomarker in patients suffering from MetS and could be used as a predictive tool to determine the degree of the underlying OxS in MetS.

[Evaluation of serum nitrite, nitrate and malondialdehyde concentrations in preeclampsia]

Preeclampsia is a complication of pregnancy that is associated with high blood pressure with an unknown etiology. There is much evidence that altered endothelial cell functions may play an important role in the pathogenesis of preeclampsia. The aims of this study were to determine serum levels of nitrite, nitrate and malondialdehyde [MDA] in pregnant women with and without preeclampsia. This observational-analytical study was performed in the third trimester of pregnancy on 35 pregnant primiparas with preeclampsia and 35 women with normal blood pressure. The women were recruited for the study among the mothers attending Andimeshk Urban Health Centers during March 2008 to March 2009. Aside from the demographic data, the gestational age and blood pressure were recorded too at the time of blood sampling. Serum levels of nitrite and nitrate were measured by Griess and MDA by thiobarbituric acid reactions. The data were statistically analyzed and compared between the two groups. Serum levels of nitrite, nitrate and MDA, respectively were 12.6 +/- 3.8, 23.8 +/- 8.6 and 9.7 +/- 2.8 micro mol/l in women with preeclampsia and 8.7 +/- 2.5 [p<0.001], 16.4 +/- 5.4 [p<0.01] and 6.34 +/- 1.6 micro mol/l [p<0.001] in the controls. The results depicted significantly higher serum concentrations of the three analyses in pregnant women with preeclampsia relative to the controls. Significantly higher serum concentrations of nitrite, nitrate and MDA in pregnant women with preeclampsia are suggestive of the role of these substances in the pathogenesis of the disease. Use of the three parameters may be useful in the early screening of preeclampsia

Time-dependent effects of ethanol on blood oxidative stress parameters and cytokines.

Alcohol consumption is implicated in the genesis of a spectrum of liver abnormalities, which are associated with a number of factors. In the present study, time-dependent effects of ethanol on cytokines (TNF-alpha, IL-2, IL-4, IL-10, IFN-gamma, VEGF-A and TGF-beta1) in serum, and blood oxidative stress parameters such as reduced glutathione content, TBARS level and activities of GPx, GR, GST, catalase and SOD in 8-10 weeks-old male BALB/c mice have been investigated. Ethanol administered @ 1.6 g/kg body wt/day significantly increased the activities of liver marker enzymes AST, ALT and ALP. Serum nitrite levels and haemolysate TBARS level also increased, while total antioxidant status in serum and GSH content in whole blood hemolysate decreased from 4th week onwards of exposure. In spite of the increased serum nitrite level and GST activity in the haemolysate, albumin level in serum, GPx and GR activities in haemolysate decreased after 12 weeks of exposure. Chronic ethanol treatment did not show any effect on IL-2, but IL-4 level was reduced and other cytokines such as IL-10, TNF-alpha, IFN-gamma, TGF-beta1 and VEGF-A levels were increased significantly after 12 weeks. The study indicates a relationship between free radical generation and immune response, and suggests that ethanol-induced liver damage is associated with oxidative stress and immunological alterations in a time-dependent manner.

Effects of medication with ivermectin, chloroquine and artemether on plasma nitrate / nitrite levels in calves naturally infected with onchocerca gutturosa

In a comparative study involving the use of Ivermectin, Chloroquine and Artemether against Onchocerca gutturosa in calves, the plasma nitrate /nitrite concentration was measured. Following treatment and clearance of skin mf of O. gutturosa, the plasma nitrate/ nitrite concentrations, nor the stable end product of Nitric Oxide [NO] breakdown, rise significantly although it showed short peaks following reduction in dermal mf counts but no clear correlation was detected

L-arginine augments the antioxidant effect of garlic against acetic acid induced ulcerative colitis in rats

Garlic contains many sulfhydryl compounds that act as antioxidants. However, the role of nitric oxide [NO] in inflammation is controversial. The aim of the present study is to investigate the possible protective effect of garlic against acetic acid-induced ulcerative colitis in rats, as well as the probable modulatory effect of L-arginine [NO precursor] on garlic activity. Intra-rectal inoculation of rats with 4% acetic acid for 3 consecutive days caused a significant increase in the colon weight and marked decrease in the colon length. In addition, acetic acid induced a significant increase in serum levels of nitrate as well as colonic tissue content of malondialdehyde [MDA]. Moreover, colonic tissue contents of glutathione [GSH], superoxide dismutase [SOD] and catalase [CAT] were markedly reduced. On the other hand, pre-treatment of rats with garlic [0.25g/kgbwt, orally] for 4 consecutive weeks and 3days during induction of colitis significantly reduced the increase in the colon weight induced by acetic acid and ameliorated alterations in oxidant and antioxidant parameters. Interestingly, oral co-administration of garlic [0.25g/kgbwt] and L-arginine [625mg/kgbwt] for the same period of garlic administration mitigated the changes in both colon weight and length induced by acetic acid and increased garlic effect on colon tissue contents of MDA and GSH. In conclusion, L-arginine can augment the protective effect of garlic against ulcerative colitis; an effect that might be mainly attributed to its NO donating property resulting in enhancement of garlic antioxidant effect. Further studies will be needed to determine which one of the active ingredients of garlic has the main antioxidant effect to be used with L-arginine

Contribuição da apnéia obstrutiva do sono para o estresse oxidativo da obesidade / Obstructive sleep apnea contribution to oxidative stress in obesity

OBJETIVO: O objetivo do trabalho foi verificar a influência da apnéia obstrutiva do sono (AOS) sobre o estresse oxidativo da obesidade e o efeito do pressão positiva de vias aéreas (CPAP) nestes pacientes. MÉTODOS: Os pacientes com IMC > 30 kg/m² foram divididos em: a) grupo 1: dez indivíduos sem AOS; b) grupo 2: dez portadores de AOS que não fizeram o uso do CPAP; e c) grupo 3: nove portadores de AOS que fizeram uso do CPAP durante dois meses. RESULTADOS: O grupo 3 apresentou, após o uso do CPAP, redução na produção de superóxido (SO) [13,2 (10,3-19,6) versus 10,5 (5,8-11,8) nmoles O2-/2×10(6) PMN] e aumento na síntese de nitritos e nitratos séricos [24,5 (16,7-33,5) versus 49,5 (39,3-58,1) µM]. Também foi verificada correlação positiva entre o índice apnéia-hipopnéia (IAH) e a produção de SO (r = 0,726) e negativa entre o IAH e os níveis de nitritos e nitratos séricos (r = -0,867). CONCLUSÕES: O estresse oxidativo presente na obesidade é exacerbado pela AOS e o uso do CPAP promove aumento nos níveis de nitritos e nitratos séricos, bem como reduções na produção de SO neste pacientes.

OBJECTIVE: The aim of this paper was to check the influence of obstructive sleep apnea (OSA) on obesity oxidative stress and CPAP (Continuous Positive Airway Pressure) effect on oxidative stress and in these patients. METHODS: Twenty nine male patients considered obese (BMI > 30kg/m²) were divided into 3 groups: a) Group I: 10 OSA free patients (apnea-hipopnea index (AHI) < 5); b) Group 2: 10 with moderate to serious OSA (AHI > 20); c) Group 3: 9 with OSA from moderate to serious (AHI > 20) using CPAP,, minimum 4 hours/night for 2 months. RESULTS: Significant differences before and after CPAP usage were observed in group 3 in the following variables: reduction of superoxide (SO) production [13,2 (10,3-19,6) vs. 10,5 (5,8-11,8) nmoles O2- /2x10(6) PMN] and increase in serum nitrite/nitrates levels [24,5 (16,7-33,5) vs. 49,5 (39,3-58,1) µM]. Positive correlation between Apnea-Hypopnea Index (AHI) and SO (r = 0,726) and negative correlation was observed between AHI and serum nitrite/nitrates levels (r = - 0,867). CONCLUSIONS: In conclusion, oxidative stress present in obesity is elevated by OSA and CPAP treatment can rise the levels of SO and can decrease serum nitrite/nitrates present in obese patients with OSA.

Effects of certain natural products in adjuvant-induced arthritis

The effects of curcumin [80 mg/kg; p.o.] and quercetin [50 mg/kg; p.o.],alone or combined, with diclofenac [2 mg/kg; i.p.] on adjuvant-induced arthritis in rats were studied and compared with diclofenac monotherapy. Experimental arthritis was induced by s.c. injection of 0.4 ml Freund's complete adjuvant [FCA] into the subplanter tissue of the right hind paw of all rats except the normal group [1% tween 80; p.o.]. The test agents were administered daily for 28 days starting from the 1[st] day of adjuvant inoculation. The control arthritic group received the vehicle [1% tween 80; p.o.] daily for the whole experiment period. Assessment of the anti-inflammatory effects of different treatments was done by measurement of paw volume before FCA injection and at different time intervals, for 28 days, thereafter using water plethysmometer. Collection of blood samples was carried out after the last paw measurement [day 28]. They were used for determination of serum lactate dehydrogenase [LDH] activity and levels of serum total antioxidants, tumor necrosis factor-alpha [TNF-alpha], interleukin-1 beta [IL-1 beta], calcium [Ca[2+]] and nitrite, a stable metabolite of nitric oxide [NO] which reflects its level. In addition, the level of thiobarbituric acid reactive substances [TBARS], as an index of lipid peroxidation was also determined. Histopathological examination of paw tissues was also carried out. Injection of FCA into the hind paw of rats induced marked arthritis manifested by paw edema during the 28-day experiment period. Treatment with diclofenac alone markedly inhibited adjuvant-induced arthritis at all the studied time intervals. Curcumin, alone, reduced FCA induced edema at day 19 only and its combination with diclofenac antagonized the anti-inflammatory effect of the latter at all the studied time intervals. Quercetin, on the other hand, reduced edema during the chronic phase of arthritis at days 19 and 28 and its combination with diclofenac antagonized the anti-inflammatory effect of the latter at day 11 only. FCA resulted in increased levels of serum TBARS, TNF-alpha, IL-1beta and nitrite as well as increased serum LDH activity. Whereas, no significant changes on serum total antioxidants or Ca[2+] levels were noted. Treatments with curcumin or quercetin alone or combined with diclofenac attenuated most of the biochemical changes elicited by FCA. Histopathological examination of paw tissues showed marked vacuolar degeneration and degradation of articular surfaces by FCA injection. Diclofenac and curcumin, alone or combined together, markedly attenuated FCA-induced histopathological changes. On the other hand, quercetin alone or in combination with diclofenac was less protective. In conclusion, the effect of diclofenac monotherapy was still superior compared to curcumin and quercetin. Effects of curcumin and quercetin seem to be mediated through influences on production of pro-inflammatory cytokines, NO level as well as lipid peroxidation

Prevalence of anaemia in Tour Sheher Zarghoon, Balochistan

Instead of communicable diseases, developing countries are now seeing serious increase in non-communicable disease and Anemia is one of major problems in developing countries like Pakistan especially in under developed areas like e.g Balochistan. Anaemia is prevalent in certain area of this continent. Anaemia is little bit prevalent in the Urban area of the Balochistan but rural and high altitude areas are still desire its due attention. The people affected belong to rural areas with low socio-economic status and are unable to afford the even economical iron therapy diagnosis, treatment. In some cases bone marrow aspirates and immunodiagnostic facilities are needed for diagnostic purpose. Results showed that prevalence of anemia was high in less than fifteen years of age group, females suffered more with anemia as compared to males in the area

Serum nitrite level and adenosine deaminase activity is altered in visceral leishmaniasis.

In this study we sought to determine if there is alteration in nitric oxide (NO) production and adenosine deaminase (ADA) activity among patients with visceral leishmaniasis (VL) and the effect of four weeks of chemotherapy on these levels. Fifty-three VL patients diagnosed clinically and by direct demonstration of the LD bodies in the bone marrow smear were studied. They were treated with Sodium Stibogluconate and sampled at the baseline and four weeks. Forty-three healthy individuals coming from the same endemic area were taken as control. Total nitrite (NO2- and NO3-) as an index of NO production and ADA activity was measured spectrophotometrically. Serum nitrite level decreased significantly in patients as compared to the healthy individuals but significantly increased following 4 weeks of chemotherapy. Conversely, Increased ADA activity was observed in the beginning of treatment and decreased significantly with successive 4 weeks of chemotherapy. It seems a negative correlation between NO level and ADA activity. This result indicates parasite induced evasion of NO and activation of T lymphocytes during immunopathogenesis of VL. Therefore, assessment of NO metabolites may be useful marker in the evaluation of the effector mechanism of macrophages and clinical manifestation of patients.

Estudos hemodinâmicos e da função endotelial em porcas saudáveis após injeção em bolus endovenoso de azul de metileno / Hemodynamic and vascular endothelium function studies in healthy pigs after intravenous bolus infusion of methylene blue / Hemodynamic and vascular endothelium function studies in healthy pigs after intravenous bolus infusion of methylene blue

OBJETIVO: Benefícios clínicos obtidos pelo azul de metileno (AM) no tratamento da vasoplegia induzida pela ação do óxido nítrico (NO) têm sido relatados na sepse, na síndrome da resposta inflamatória sistêmica (SIRS) em cirurgia cardíaca e no choque anafilático, mas a sua segurança é muitas vezes questionada, principalmente relacionada aos seus efeitos hemodinâmicos e à possibilidade de causar disfunção endotelial. O objetivo deste estudo foi examinar os efeitos hemodinâmicos e a função endotelial da infusão endovenosa in vivo do AM em porcos. MÉTODOS: O protocolo de estudo incluiu dois grupos experimentais de porcas fêmeas: Grupo I (Controle) - os animais (n = 6) não receberam AM; Grupo II (AM) - os animais receberam 3 mg/kg de AM em forma de bolus endovenoso. Após quinze minutos de registro dos parâmetros hemodinâmicos os animais foram sacrificados por exsangüinação, e os estudos in vitro foram conduzidos usando segmentos de artérias coronária, hepática, mesentérica superior, renal, para determinar o efeito do AM na função endotelial relacionada com a liberação de NO. Mediu-se também o NO plasmático nos dois grupos experimentais. RESULTADOS: Os resultados obtidos no presente estudo foram: 1) a infusão endovenosa de AM (3,0 mg/kg) não causou nenhuma alteração hemodinâmica significativa; 2) os valores absolutos e porcentuais e nitrito/nitrato plasmático (NOx) não apresentaram diferenças nos dois grupos experimentais; 3) o estudo in vitro dos segmentos arteriais (coronária, hepática, renal e mesentérica superior) não apresentou disfunção endotelial nos dois grupos. Os resultados sugerem que a injeção endovenosa de AM é segura. Esse dado concorda com dados clínicos no qual o AM foi utilizado para tratar a síndrome vasoplégica após circulação extracorpórea, síndrome da resposta infamatória sistêmica (SIRS) e anafilaxia. Os resultados não foram inesperados porque os animais não apresentavam vasoplegia, não se esperando que a inibição da guanilatociclase tenha algum efeito...

OBJECTIVE: Clinical benefit of methylene blue (MB) treating NO-induced vasoplegia has been reported in sepsis, systemic inflammatory response syndrome (SIRS) in cardiac surgery and anaphylactic shock, but its safety is sometimes questioned, mainly regarding its hemodynamic effects and the possibility of causing endothelium dysfunction. To examine the nitric oxide plasma levels and cardiovascular effects of the infusion of MB in vivo and its effects on endothelium-dependent and endothelium-independent in vitro vascular relaxation. METHODS: The study protocol included two experimental groups of female pigs: Group I (Control) - the animals (n=6) did not receive MB; Group II (MB) - the animals received 3 mg/kg of MB intravenous bolus infusion. After fifteen minutes of hemodynamic parameter recording the animals were sacrificed by exsanguination, and in vitro studies were conducted using segments of coronary, hepatic, superior mesenteric and renal arteries, to determine the effect of MB on the arterial endothelium function with regard to NO release. Nitric oxide plasma levels (NOx) were measured in each of the experimental groups. RESULTS: The results obtained in the present investigation were: 1) intravenous infusion of MB (3.0 mg/kg) caused no hemodynamic changes; 2) absolute and percent plasma NOx values did not differ between the experimental groups; and 3) in vitro study of vascular relaxation showed no significant difference between groups. These results show that MB intravenous infusion seems to be safe. This finding agrees with data from clinical experiments where MB was used to treat vasoplegic syndrome after cardiopulmonary bypass, systemic inflammatory response syndrome (SIRS) and anaphylaxis. These results were not unexpected because, as in healthy subjects, hemodynamics is only fine tuned and not fully under NO control; therefore, MB inhibiting guanylyl cyclase is not expected to do anything...

Evidence for the participation of nitric oxide in pemphigus

Pemphigus is an inflammatory autoimmune disorder of the skin. Nitric oxide (NO) is an inflammatory mediator linked to a variety of physiological and pathophysiological phenomena that include skin tumors, psoriasis, urticaria, and atopic dermatitis. Inflammatory cells present in pemphigus lesions are important sources of NO production. We investigated whether NO is involved in pemphigus. A prospective cohort study was conducted at the Dermatology Service of the Hospital Universitário Walter Cantídio of the Federal University of Ceará. All patients seen at the outpatient clinic between August 2000 and July 2001, with a clinically and histologically confirmed diagnosis of pemphigus were included. The median age was 42.5 years (range: 12-69 years) with a male to female ratio of 3:2. Total serum nitrite levels, used as a marker for NO production, were determined by the Griess reaction. Skin biopsies from pemphigus and breast surgery (control) patients were used for the detection of the inducible NO synthase (iNOS) by immunohistochemistry. Twenty-two (22) patients with pemphigus and eight (8) controls who did not differ in demographic characteristics were included. Total serum nitrite levels were significantly higher (>7 æmol/L) in pemphigus patients compared to controls (<6 æmol/L), regardless of the severity of the clinical activity of pemphigus (P < 0.0001). All pemphigus biopsies presented increased immunostaining for iNOS that was not detected in normal skin samples. These data are the first to demonstrate that pemphigus patients display increased serum NO levels that are associated with increased iNOS expression in the affected skin.

Plasma levels of adrenomedullin and total nitrite in infants and children with heart failure

Localization of adrenomedullin [ADM] in peripheral tissues, including the heart, kidney, and vasculature, suggests an important role for the peptide as a regulator of cardiovascular function. ADM has hemodynamic effects including vasodilation, increases in cardiac contractility cardiac output, diuresis, and natriuresis. These effects may incorporate many of the therapeutic goals of heart failure management. The aim of our study was to find a relation between plasma level of ADM and Nitric Oxide [NO] in heat failure, with special interests to the type of heart disease, age, sex of patients, and severity of heart failure. We compared plasma levels of ADM and Nitric oxide [NO] in three groups of patients with heart failure: 14 patients diagnosed as rheumatic heart disease [RHD] [group I], 10 patients diagnosed as congenital heart disease [CHD] [group II], 6 patients diagnosed as dilated cardiomyopathy [DCM] [group III] and 20 apparently healthy children who were taken as controls [group IV]. Patients with heart failure had significantly higher levels of ADM and NO than controls [p=0.0001]. ADM and NO were highest among the patients with heart failure due to RHD then congenital heart disease and lastly dilated cardiomyopathy respectively [P=0.02 and 0.04 respectively]. We concluded that ADM is a biochemical marker for evaluating the severity of heart failure, and may be a new and promising approach for the treatment of patients with heart failure and pulmonary hypertension in children. In the future, insights into the role of NO in cardiac remodeling should allow the development of novel therapeutic strategies to treat cardiac remodeling and failure in infants and children

Potential prophylactic role of nitric oxide synthase inhibitors on experimentally induced cataract in rats

Nitric oxide [NO] has been related to numerous eye diseases such as cataract. In the present study, we investigated and compared the prophylactic role of selective and nonselective nitric oxide synthase [NOS] inhibitors on the development of selenite induced cataract in rats. The study comprised seven groups; of which four groups served as controls. Cataract was induced in three groups by a single subcutaneous injection of sodium selenite [4mg/kg] in 13-days old Lewis rats. One group was left untreated. The other two groups were treated with aminoguanidine or L-NAME [N G-nitro-L-arginine methyl ester] in a dose of 60mg/kg/day orally for nine days and treatment started two days before selenite injection. Slit lamp examination was done daily to detect lens opacity. Biochemical analysis of lenses was done seven days after selenite injection and included concentrations of nitrite, glutathione, calcium and soluble proteins, in addition to, Cellogel electrophoresis of soluble lens proteins. Ophthalmologic and biochemical results revealed a noticeable prophylactic role of both drugs on selenite cataract development after seven days of selenite injection. In addition, it was observed that aminoguanidine had a better protective role than L-NAME. It can be concluded that NO had an important role in the development of selenite induced cataract in rats since inhibitors of NOS could prevent the development of selenite cataract

Neurohormonal changes in medical students during academic srtess

Academic stress is a good model of psychological stress in humans and is thus useful for studying psychoneurohormonal changes. The aim of the current study was to examine the effect of academic examination stress on activation of the hypothalamus-autonomic nervous system [HANS] and the hypothalamic-pituitary-adrenocortical [HPA] axis, through the measurements of changes in neuro-hormones during final exams as compared to the pre-exam baseline. Forty-eight first- and second-year female medical students participated. Plasma leptin, neuropeptide Y [NPY], nitrite, nitrate, andrenomedullin, cortisol and adrenocorticotropic hormone [ACTH] were measured at baseline and during final examinations. Plasma levels of cortisol, ACTH, NPY, adrenomedullin, nitrite and nitrate increased during times of academic stress as compared to baseline levels. However, only plasma leptin level was decreased during the academic stress as compared to baseline, probably through a negative feedback mechanism resulting from sympathetic stimulation. The results indicate that both the HANS and HPA are involved in this type of stress and both are activated at the same time. Academic stress induced significant neurohormonal changes. Leptin, NPY, nitrite, nitrate, adrenomedullin, cortisol and ACTH can be considered part of a complex mosaic model of the neuroendocrine system during academic stress