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Nitric oxide (NO) is a gaseous signaling molecule that plays an important role in myriad physiological processes, including the regulation of vascular tone, neurotransmission, mitochondrial respiration, and skeletal muscle contractile function. NO may be produced via the canonical NO synthase-catalyzed oxidation of l-arginine and also by the sequential reduction of nitrate to nitrite and then NO. The body's nitrate stores can be augmented by the ingestion of nitrate-rich foods (primarily green leafy vegetables). NO bioavailability is greatly enhanced by the activity of bacteria residing in the mouth, which reduce nitrate to nitrite, thereby increasing the concentration of circulating nitrite, which can be reduced further to NO in regions of low oxygen availability. Recent investigations have focused on promoting this nitrate-nitrite-NO pathway to positively affect indices of cardiovascular health and exercise tolerance. It has been reported that dietary nitrate supplementation with beetroot juice lowers blood pressure in hypertensive patients, and sodium nitrite supplementation improves vascular endothelial function and reduces the stiffening of large elastic arteries in older humans. Nitrate supplementation has also been shown to enhance skeletal muscle function and to improve exercise performance in some circumstances. Recently, it has been established that nitrate concentration in skeletal muscle is much higher than that in blood and that muscle nitrate stores are exquisitely sensitive to dietary nitrate supplementation and deprivation. In this review, we consider the possibility that nitrate represents an essential storage form of NO and discuss the integrated function of the oral microbiome, circulation, and skeletal muscle in nitrate-nitrite-NO metabolism, as well as the practical relevance for health and performance.

Extensive research performed over the past 10 years has resulted in dietary nitrate being considered a nutritional supplement that can improve exercise performance. However, there is still limited insight in the metabolic fate of dietary nitrate following the appearance of nitrate and nitrite in the circulation. Recent observations in humans suggest the storage of nitrate in skeletal muscle tissue. This short review discusses the possibility of nitrate being stored and utilized in human skeletal muscle tissue, and why confirming this may increase our understanding of how the nitrate -nitrite -NO pathway improves exercise performance. Further insight in skeletal muscle nitrate storage and metabolism may provide answers to current gaps in knowledge, such as the ergogenic benefit of acute vs multiday dietary nitrate supplementation, as well as the suggested muscle fiber -type specific effects on exercise performance. In this mini -review, specific questions that need further exploration are also discussed.

Objective Diterpene alkaloids are secondary plant metabolites and chemotaxonomical markers with a strong biological activity. These compounds are characteristic for the Ranunculaceae family, while their occurrence in other taxa is rare. Several species of the Spiraea genus (Rosaceae) are examples of this rarity. Screening Spiraea species for alkaloid content is a chemotaxonomical approach to clarify the classification and phylogeny of the genus. Novel pharmacological findings make further investigations of Spiraea diterpene alkaloids promising. Results Seven Spiraea species were screened for diterpene alkaloids. Phytochemical and pharmacological investigations were performed on Spiraea chamaedryfolia, the species found to contain diterpene alkaloids. Its alkaloid-rich fractions were found to exert a remarkable xanthine-oxidase inhibitory activity and a moderate antibacterial activity. The alkaloid distribution within the root was clarified by microscopic techniques. Electronic supplementary material The online version of this article (10.1186/s13104-017-3013-y) contains supplementary material, which is available to authorized users.

Objective: Accumulation of reactive oxygen species by increased uric acid production has been suggested as a possible underlying mechanism for the association between uric acid and high blood pressure (BP). We, therefore, investigated the association between serum uric acid concentration and 24-h urinary uric acid excretion, as proxy for uric acid production, with ambulatory 24-h blood pressure and hypertension. Methods: Cross-sectional analyses were conducted among 2555 individuals [52% men, mean age 60.0 ± 8.2 years; 27% type 2 diabetes (by design)] from The Maastricht Study. Multivariable regression analyses were performed to investigate the association of serum uric acid and 24-h urinary uric acid excretion with 24-h pulse pressure, 24-h mean arterial pressure (MAP), and hypertension. Results: After adjustment for traditional hypertension risk factors, serum uric acid concentration (per SD of 81 μmol/l) was associated with higher 24-h MAP [β 0.63 mmHg; confidence interval (CI) 0.27-1.00] and positively associated with hypertension (odds ratio 1.43; CI 1.27-1.61). Urinary uric acid excretion (per SD of 140 mg/day/1.73 m) was associated with higher 24-h MAP (β 0.79 mmHg; CI 0.46-1.12) and with hypertension (odds ratio 1.13; CI 1.02-1.25). There was no significant association between serum and 24-h urinary uric acid excretion with 24-h pulse pressure. There was no interaction with sex or age for the aforementioned associations. Conclusion: Higher serum and urinary uric acid concentrations were associated with higher 24-h MAP and hypertension. These results suggest that serum and 24-urinary uric acid concentrations, the latter as proxy for uric acid production are, independent of each other, associated with BP and hypertension.

Objective: Elevated serum uric acid concentration has been associated with high blood pressure (BP) and hypertension. A putative underlying mechanism is the accumulation of reactive oxygen species when uric acid is generated by an increased enzyme activity of xanthine oxidase (XO). The aims of the present study were to investigate the associations between plasma uric acid concentration, purine metabolite ratios, as proxies for increased XO activity, and SBP and DBP in school-age children.Methods: Cross-sectional analyses were performed in 246 children (46% boys; mean age 7.1 years) from the Dutch KOALA Birth Cohort Study. Purine metabolites were determined with ultra-performance liquid chromatography-tandem mass spectrometry. During a home visit, a nurse collected a blood sample and measured BP three times; in addition, parents measured their child's BP on three consecutive days, in the morning and evening. Generalized estimating equations were used for analyses while controlling for variables such as sex, age, BMI, physical activity, and dietary intake.Results: In multivariable analysis, uric acid (per SD of 38 mu mol/l) was associated with DBP z-scores [ s beta 0.07; confidence interval (CI), 0.01-1.14], but not with SBP z-scores. Higher ratios of uric acid/xanthine (per SD of 138) (s beta 0.09; CI, 0.01-0.17) and xanthine/hypoxanthine (per SD of 321) (s beta 0.08; CI, 0.02-0.17) were associated with higher DBP z-scores, but not with SBP z-scores.Conclusion: In school-age children, uric acid and the ratios of uric acid/xanthine and xanthine/hypoxanthine were significantly associated with DBP z-scores. Suggesting that, both uric acid concentration and increased XO activity are associated with BP.

Production of considerable amounts of reactive oxygen species (ROS) eventually leads to oxidative stress. A key role of oxidative stress is evident in the pathologic mechanisms of endothelial dysfunction and associated cardiovascular diseases. Vascular enzymes such as NADPH oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide synthase are involved in the production of ROS. The question remains whether pharmacologic approaches can effectively combat the excessive ROS production in the vasculature. Interestingly, existing registered cardiovascular drugs can directly or indirectly act as antioxidants, thereby preventing the damaging effects of ROS. Moreover, new compounds targeting NADPH oxidases have been developed. Finally, food-derived compounds appear to be effective inhibitors of oxidative stress and preserve vascular function.

Objectives: Allopurinol is a uric acid lowering drug used in the treatment of gout and the prevention of tumor lysis syndrome. Allopurinol and its active metabolite oxipurinol inhibit xanthine oxidase, which forms uric acid from xanthine and hypoxanthine. Therapeutic drug monitoring is an important option for evaluation and optimization of allopurinol treatment in case of renal impairment, interaction with uricosuric drugs or to verify patient adherence. In this study we developed and validated a simple quantitative assay using reverse phased high-performance liquid chromatography (HPLC) with UV-detection as a method for quantification of allopurinol and oxipurimol in human serum in the presence of different frequently used drugs.Methods: The HPLC-UV method uses a mobile phase consisting of sodium acetate (0.02 M; pH 4.5), at a flow rate of 1.0 mL/min. Allopurinol and oxipurinol are detected by UV-absorption at 254 nm with a retention time of 9.9 min for oxipurinol and 12.3 min for allopurinol. Aciclovir is used as internal standard.Results: Validation showed for allopurinol lower and upper limits of quantification of 0.5 and 10mg/L and for oxipurinol I and 40mg/L, respectively. The assay was linear over the concentration range of 0.5-10mg/L (allopurinol) and 1-40mg/L (oxipurinol). Intra- and inter-day precision showed coefficients of variation 1.5. Exogenous purine-like compounds and co-medication frequently used by gout patients did not hinder the analysis due to the dichloromethane washing step or to low UV-absorpion at 253 nm. Serum levels of 66 patients prescribed allopurinol 300 mg/day were determined using this HPLC-UV method. Measured serum allopurinol and oxipurinol concentrations in clinical practice showed large variability with a range of Conclusion: We developed an easy-to-operate and validated HPLC-UV method for the quantification of allopurinol and oxipurinol in human serum. This method was proven to be valid for samples of gout patients frequently using concomitant medications. (c) 2007 Elsevier B.V. All rights reserved.

In this study, hydrogen peroxide (H2O2) sensitive Al doped ZO(AZO)/Au thin film electrode has been developed for the utilization as a biosensor. A preferred c-axis oriented AZO/Au thin film was deposited on quartz substrate by RF magnetron sputtering at room temperature. Structural, morphological and optical properties of the AZO film were analyzed by X-ray diffraction, atomic force microscopy and photoluminescence. The sensor performance was characterized by electrochemical analysis device. The sensibility of prepared thin film electrodes to H2O2 was studied. The dependence of amperometric response current on the glucose and cholesterol concentrations was also investigated.

PURPOSE: To study the role of methylene blue as an inhibitor of superoxide production by xanthine oxidase. METHODS: Thirty-two Wistar rats were divided into 2 groups of 16 animals: the control group and the experimental group. All were submitted to a laparotomy for the occlusion of the cranial mesenteric artery during 60 minutes. The reperfusion was confirmed by the pulsation of the artery after the release of the temporary ligature and color change of the intestines. In the animals of the control group, 2 ml of saline were injected in the peritoneal cavity and in the animals of the experimental group, 2 ml of methylene blue were injected in the peritoneal cavity. After reperfusion for 4 hours, the animals were then sacrificed. The lungs were excised from all 32 rats. Simultaneously, the small intestine and kidneys were ressected in 20 animals (10 from the control group and 10 from the experimental group). Samples of the organs were taken to evaluate the action of xanthine-oxidase, for histopathology studies and for characterization of the edema. RESULTS: In the animals of the experimental group, the inflammatory lesion as well as the edema in the lung was greater than in the control group. The intestinal and renal lesions were similar in both groups, but the lung damage was superior to that observed in the intestines and kidneys. . CONCLUSION: Despite similar action of the xanthine oxidase in the control and the experimental group, after intestinal ischemia and reperfusion, the protective effect of methylene blue was observed only in the lungs of the experimental group. OBJETIVO: Estudar a ação do azul de metileno como supressor da produção de radicais livres de oxigênio, atuando como receptor alternativo de elétrons na enzima xantina-oxidase. MATERIAIS E MÉTODOS: Foram utilizados 32 ratos Wistar (Rattus norvegicus albinus, Rodentia mammalia) divididos em 2 grupos de 16 animais, os quais foram denominados grupos: experimento e controle. Todos os animais foram submetidos a laparotomia mediana e oclusão da artéria mesentérica cranial por 60 minutos. A reperfusão foi confirmada por meio da verificação do reaparecimento da pulsação da arcada mesentérica. Foi então administrado no grupo experimento 2 ml de azul de metileno 1% intra-peritonealmente, enquanto que no grupo controle o mesmo volume de solução salina isotônica foi administrado pela mesma via. Após 4 horas de reperfusão, os animais foram sacrificados. Os pulmões foram ressecados nos 32 animais do estudo, ao passo que o intestino delgado e os rins em 20 animais (10 ratos do grupo controle e 10 ratos do grupo experimento). Amostras dos órgãos retirados foram obtidas para medição da xantina-oxidase, análise histopatológica e avaliação do edema. RESULTADOS: O dano pulmonar encontrado no grupo controle foi superior ao encontrado no grupo experimento. Observou-se uma maior formação de edema e uma maior atividade inflamatória nos pulmões do grupo controle. O dano intestinal e renal encontrado foi semelhante em ambos os grupos, mas não tão intenso quanto o dano pulmonar. A atividade da xantina-oxidase foi semelhante em ambos os grupos. CONCLUSÃO: A atividade protetora do azul de metileno foi evidenciada nos pulmões, todavia o mesmo efeito não foi demonstrado nos rins nem no intestino delgado.