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Aim: Chronic anal fissures (CAFs) are frequently encountered in coloproctology clinics. Chemical sphincterotomy with pharmacological agents is recommended as first-line therapy. Topical nitrates (TN) heal CAF effectively but recurrences are common. An alternative treatment modality is injection of botulinum toxin (BT) into the anal sphincter. We aimed to perform an updated systematic review and meta-analysis to compare the effectiveness of BT and TN in the management of CAF., Method: PubMed, EMBASE and Cochrane databases were searched for relevant articles from inception until March 2017. All randomized controlled trials (RCTs) that reported direct comparisons of BT and TN were included. Two independent reviewers performed methodological assessment and data extraction. Random effects models were used to calculate pooled effect size estimates., Results: Six RCTs describing 393 patients (194 BT, 199 TN) were included. There was significant heterogeneity among the trials. On random effects analysis there were no significant differences in incomplete fissure healing (OR = 0.47, 95% CI 0.13-1.68, P = 0.24) or recurrence (OR = 0.70, 95% CI 0.39-1.25, P = 0.22) between BT and TN, respectively. BT was associated with a higher rate of transient anal incontinence (OR = 2.53, 95% CI 0.98-6.57, P = 0.06) but significantly fewer total side effects (OR = 0.12, 95% CI 0.02-0.63, P = 0.01) and headache (OR = 0.10, 95% CI 0.02-0.60, P = 0.01) compared with TN., Conclusion: BT is associated with fewer side effects than TN but there is no difference in fissure healing or recurrence. Patients need to be warned regarding the risk of transient anal incontinence associated with BT., (Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.)

Aging is associated with increased peripheral chemoreceptor activity, reduced nitric oxide (NO) bioavailability, and attenuation of cardiovagal baroreflex sensitivity (BRS), collectively increasing the risk of cardiovascular disease. Evidence suggests that NO may attenuate peripheral chemoreflex sensitivity and increase BRS. Exogenous inorganic nitrate ([Formula: see text]) increases NO bioavailability via the [Formula: see text]-[Formula: see text]-NO pathway. Our hypothesis was that inorganic [Formula: see text] supplementation would attenuate peripheral chemoreflex sensitivity and enhance spontaneous cardiovagal BRS in older adults. We used a randomized, placebo-controlled crossover design in which 13 older (67 ± 3 yr old) adults ingested beetroot powder containing (BR A ) or devoid of (BR P ) [Formula: see text] and [Formula: see text] daily over 4 wk. Spontaneous cardiovagal BRS was assessed over 15 min of rest and was quantified using the sequence method. Chemoreflex sensitivity was assessed via ~5 min of hypoxia (10% fraction of inspired O 2 ) and reported as the slope of the relationship between O 2 saturation (%[Formula: see text]) and minute ventilation (in l/min) or heart rate (in beats/min). Ventilatory responsiveness to hypoxia was reduced after BR A (from -0.14 ± 0.04 to -0.05 ± 0.02 l·min -1 ·%[Formula: see text] -1 , P = 0.01) versus BR P (from -0.10 ± 0.05 to -0.11 ± 0.05 l·min -1 ·%[Formula: see text] -1 , P = 0.80), with no differences in heart rate responsiveness (BR A : from -0.47 ± 0.06 to -0.33 ± 0.04 beats·min -1 ·%[Formula: see text] -1 , BR P : from -0.48 ± 0.07 to -0.42 ± 0.06 beats·min -1 ·%[Formula: see text] -1 ) between conditions (interaction effect, P = 0.41). Spontaneous cardiovagal BRS was unchanged after BR A and BR P (interaction effects, P = 0.69, 0.94, and 0.39 for all, up, and down sequences, respectively), despite a reduction in resting systolic and mean arterial blood pressure in the experimental (BR A ) group ( P < 0.01 for both). These findings illustrate that inorganic [Formula: see text] supplementation attenuates peripheral chemoreflex sensitivity without concomitant change in spontaneous cardiovagal BRS in older adults. NEW & NOTEWORTHY Exogenous inorganic nitrate supplementation attenuates ventilatory, but not heart rate, responsiveness to abbreviated hypoxic exposure in older adults. Additionally, inorganic nitrate reduces systolic and mean arterial blood pressure without affecting spontaneous cardiovagal baroreflex sensitivity. These findings suggest that inorganic nitrate may attenuate sympathetically oriented pathologies associated with aging.

Rationale: Impact of ambient pollution upon children's asthma may differ by sex, and exposure dose and timing. Psychosocial stress can also modify pollutant effects. These associations have not been examined for in utero ambient nitrate exposure., Objectives: We implemented Bayesian-distributed lag interaction models to identify sensitive prenatal windows for the influence of nitrate (NO 3 - ) on child asthma, accounting for effect modification by sex and stress., Methods: Analyses included 752 mother-child dyads. Daily ambient NO 3 - exposure during pregnancy was derived using a hybrid chemical transport (Geos-Chem)/land-use regression model and natural log transformed. Prenatal maternal stress was indexed by a negative life events score (high [>2] vs. low [≤2]). The outcome was clinician-diagnosed asthma by age 6 years., Measurements and Main Results: Most mothers were Hispanic (54%) or black (29%), had a high school education or less (66%), never smoked (80%), and reported low prenatal stress (58%); 15% of children developed asthma. BDILMs adjusted for maternal age, race, education, prepregnancy obesity, atopy, and smoking status identified two sensitive windows (7-19 and 33-40 wk gestation), during which increased NO 3 - was associated with greater odds of asthma, specifically among boys born to mothers reporting high prenatal stress. Cumulative effects of NO 3 - across pregnancy were also significant in this subgroup (odds ratio = 2.64, 95% confidence interval = 1.27-5.39; per interquartile range increase in ln NO 3 - )., Conclusions: Prenatal NO 3 - exposure during distinct sensitive windows was associated with incident asthma in boys concurrently exposed to high prenatal stress.

Dietary nitrate is mainly obtained from vegetables, especially green leafy vegetables and beetroot. As a result of early research, dietary nitrate is currently viewed as a contaminant linked to increased risks of stomach cancer and methaemoglobinaemia. Consequently, nitrate levels are restricted in certain vegetables and in water supplies to ensure exposure levels remain below an acceptable daily intake of 3·7 mg/kg per d. The average nitrate intake in the UK is approximately 70 mg/d, although some population groups, such as vegetarians, may consume three times that amount. However, recent studies in the last decade suggest that dietary nitrate can significantly reduce systolic blood pressure via the nitrate-nitrite-NO pathway. A small, downward shift in systolic blood pressure across the population could significantly reduce the incidence of hypertension and mortality from CVD such as stroke. Interestingly, vegetarians tend to have lower levels of blood pressure than omnivores and epidemiological studies suggest that vegetarians have lower risks of CVD. Recent evidence is mainly focused on the acute effects of dietary nitrate supplementation and there is a lack of data looking at the chronic effects of high nitrate consumption in humans. Nevertheless, due to potential health benefits, some authors are recommending that nitrate should be considered as a nutrient necessary for health, rather than as a contaminant which needs to be restricted. This review will discuss the emerging role of dietary nitrate in the control of blood pressure and whether there is sufficient evidence to state that nitrate is a 'new' nutrient.

Objective: The evidence is limited about the potentially different health effects of various chemical constituents of fine particulate matter (PM 2.5 ). We thus assessed the acute effects of various chemical constituents of PM 2.5 on blood pressure (BP)., Methods: We performed a longitudinal panel study with six repeated visits in 28 urban residents with chronic obstructive pulmonary disease in Shanghai, China from May to July, 2014. Twelve (43%) of them took antihypertensive medications. We measured resting BP by using a mercury sphygmomanometer and monitored real-time concentrations of PM 2.5 constituents at a nearby site. Based on the linear mixed-effects model, we evaluated the effects of 10 major constituents in PM 2.5 on BP, using a single-constituent model and a constituent-residual model after accounting for the multicollinearity., Results: We obtained a total of 168 pairs of effective BP measurements during the study period. There are moderate or high correlations among various PM 2.5 constituents. An interquartile range increase of PM 2.5 (19.1μg/m 3 ) was associated with increments of 1.90mmHg [95% confidence interval (CI): 0.66, 3.13] in systolic BP, 0.68mmHg (95%CI: -0.02, 1.37) in diastolic BP and 1.23mmHg (95%CI: 0.19, 2.29) in pulse pressure. Some constituents of PM 2.5 , including organic carbon, elemental carbon, nitrate and ammonium, were robustly associated with elevated BP after controlling for total PM 2.5 mass and accounting for multi-collinearity. Two constituents (magnesium and calcium) were associated with decreased BP., Conclusions: Organic carbon, elemental carbon, nitrate and ammonium may be mainly responsible for elevated BP from a short-term exposure to PM 2.5 ., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Morphine, oxygen, and nitrates are time-honored therapies for the initial management of acute coronary syndrome (ACS). The traditional goal of these agents in ACS has been to (1) relieve symptoms, (2) prevent infarction or limit its size, and (3) improve outcomes, both acutely and during follow-up. Despite their ongoing use in routine ACS care, nitrates, morphine, and oxygen have no evidence of clinical outcomes benefit from randomized trials. Furthermore, emerging data have recently suggested that, in certain situations, morphine and oxygen may actually be associated with harm in the setting of ACS. In this review article, we thoroughly examine updated evidence for each of these acute-phase ACS agents with respect to their individual risks and benefits. We review guideline recommendations for these therapies and outline future directions for their use in clinical practice., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Groundwater nitrate contamination from agriculture is of paramount environmental interest. A continuous consumption of polluted water as drinking water or for culinary purposes is by no means a minor hazard for people's health that must be studied. This research presents a new methodology for the spatial analysis of health risk rate from intake of nitrate-polluted groundwater. The method is illustrated through its application to a water quality sampling campaign performed in the south of Spain in 2003. The probability risk model used by the US Environmental Protection Agency has been applied, considering a residential intake framework and three representative population age groups (10, 40 and 65 years).The method was based upon coupling Monte Carlo simulations and geostatistics, which allowed mapping of the health risk coefficient (RC). The maps obtained were interpreted in the framework of water resources management and user's health protection (municipalities). The results showed waterborne health risk caused by nitrate-polluted water is moderately low for the region. The observed risk was larger for the elderly and children, although no significant differences were found among the three age groups (RC average values of 95th percentile for age of 0.37, 0.33 and 0.37, respectively). Significant risk values of RC > 1 were obtained for 10 % of the surface in the NW site of the study area, where the municipalities with the highest contamination thresholds are located (agricultural activity). Nitrate concentration and intake rate stood out as the main explanatory variables of the RC.

Background: In this double-blind randomized placebo-controlled crossover trial, we investigated whether oral sodium nitrate, when added to existing background medication, reduces exertional ischemia in patients with angina., Methods and Results: Seventy patients with stable angina, positive electrocardiogram treadmill test, and either angiographic or functional test evidence of significant ischemic heart disease were randomized to receive oral treatment with either placebo or sodium nitrate (600 mg; 7 mmol) for 7 to 10 days, followed by a 2-week washout period before crossing over to the other treatment (n=34 placebo-nitrate, n=36 nitrate-placebo). At baseline and at the end of each treatment, patients underwent modified Bruce electrocardiogram treadmill test, modified Seattle Questionnaire, and subgroups were investigated with dobutamine stress, echocardiogram, and blood tests. The primary outcome was time to 1 mm ST depression on electrocardiogram treadmill test. Compared with placebo, inorganic nitrate treatment tended to increase the primary outcome exercise time to 1 mm ST segment depression (645.6 [603.1, 688.0] seconds versus 661.2 [6183, 704.0] seconds, P =0.10) and significantly increased total exercise time (744.4 [702.4, 786.4] seconds versus 760.9 [719.5, 802.2] seconds, P =0.04; mean [95% confidence interval]). Nitrate treatment robustly increased plasma nitrate (18.3 [15.2, 21.5] versus 297.6 [218.4, 376.8] μmol/L, P <0.0001) and almost doubled circulating nitrite concentrations (346 [285, 405] versus 552 [398, 706] nmol/L, P =0.003; placebo versus nitrate treatment). Other secondary outcomes were not significantly altered by the intervention. Patients on antacid medication appeared to benefit less from nitrate supplementation., Conclusions: Sodium nitrate treatment may confer a modest exercise capacity benefit in patients with chronic angina who are taking other background medication., Clinical Trial Registration: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02078921. EudraCT number: 2012-000196-17., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: N-nitroso compounds formed endogenously after nitrate/nitrite ingestion are animal renal carcinogens. Previous epidemiologic studies of drinking water nitrate did not evaluate other potentially toxic water contaminants, including the suspected renal carcinogen chloroform., Methods: In a cohort of postmenopausal women in Iowa (1986-2010), we used historical measurements to estimate long-term average concentrations of nitrate-nitrogen (NO3-N) and disinfection by-products (DBP) in public water supplies. For NO3-N and the regulated DBP (total trihalomethanes [THM] and the sum of five haloacetic acids [HAA5]), we estimated the number of years of exposure above one-half the current maximum contaminant level (>½-MCL NO3-N; >5 mg/L). Dietary intakes were assessed via food frequency questionnaire. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox models, and evaluated interactions with factors influencing N-nitroso compound formation., Results: We identified 125 incident kidney cancers among 15,577 women reporting using water from public supplies >10 years. In multivariable models, risk was higher in the 95th percentile of average NO3-N (HRp95vsQ1 = 2.3; CI: 1.2, 4.3; Ptrend = 0.33) and for any years of exposure >½-MCL; adjustment for total THM did not materially change these associations. There were no independent relationships with total THM, individual THMs chloroform and bromodichloromethane, or with haloacetic acids. Dietary analyses yielded associations with high nitrite intake from processed meats but not nitrate or nitrite overall. We found no interactions., Conclusions: Relatively high nitrate levels in public water supplies were associated with increased risk of renal cancer. Our results also suggest that nitrite from processed meat is a renal cancer risk factor.

Due to the large number of drugs now available, the therapy of erectile dysfunction has changed profoundly in recent decades. The phosphodiesterase type 5 inhibitors (PDE5-i): sildenafil, taldalafil, vardenafil, and avanafil are EMA European Medicines Agency approved and show similar adverse events and success rates. The absolute contraindication is the simultaneous use of nitrates. Despite this wide variety of options, therapy of erectile dysfunction should be performed in an individually adapted manner. The exact patient's history, physical examination, collaboration of medical disciplines, and choice of therapy will offer every patient the possibility to achieve or regain a satisfying sexual life.

Background: Nitrates may be beneficial in heart failure with preserved ejection fraction (HFpEF) by enhancing cGMP signaling and improving hemodynamics, but real-world data on potential efficacy are lacking., Methods and Results: We linked the Swedish Heart Failure Registry to national registries with International Classification of Diseases, Tenth Revision comorbidity diagnoses and demographic and socioeconomic data. In HFpEF, defined as left ventricular ejection fraction ≥40%, we derived propensity scores for nitrate use using 52 baseline variables. The association between nitrate use and all-cause mortality and the composite of all-cause mortality or first heart failure hospitalization was assessed in a cohort matched 2:1 untreated to treated based on age and propensity score. In the overall HFpEF cohort (n=19 047; mean [SD] age, 76 [12] years; 46% women), nitrates were used in 17%, and the crude 1-year survival for treated versus untreated patients was 79% (95% confidence interval [CI], 78%-80%) versus 84% (95% CI, 83%-84%) respectively; hazard ratio was 1.48 (95% CI, 1.40-1.56; P <0.001) during a median 755-day follow-up. Matching yielded 2235 treated versus 4470 untreated patients, with 1-year survival of 80% (95% CI, 78%-82%) versus 79% (95% CI, 78%-81%) and hazard ratio of 1.06 (95% CI, 0.98-1.15; P =0.12). Nitrates were associated with worse composite outcome in the matched HFpEF cohort, with 1-year event-free survival of 62% (95% CI, 60%-64%) versus 65% (95% CI, 63%-66%) and hazard ratio of 1.11 (95% CI, 1.04-1.18; P =0.003). These patterns were reproduced in several consistency analyses., Conclusions: In HFpEF, the use of nitrates was not associated with improvements in all-cause mortality or heart failure hospitalization., (© 2017 American Heart Association, Inc.)

Purpose: This study evaluated the effects of dietary nitrate (NO 3 - ) supplementation on physiological functioning and exercise performance in trained runners/triathletes conducting short and longer-distance treadmill running time-trials (TT)., Method: Eight trained male runners or triathletes completed four exercise performance tests comprising a 10 min warm up followed by either a 1500 or 10,000 m treadmill TT. Exercise performance tests were preceded 3 h before the exercise by supplementation with either 140 ml concentrated nitrate-rich (~12.5 mmol nitrate) (BRJ) or nitrate-deplete (~0.01 mmol nitrate) (PLA) beetroot juice., Results: BRJ supplementation significantly elevated plasma [NO 2 - ] (P < 0.05). Resting blood pressure and exercise [Formula: see text] were not significantly different between BRJ and PLA (P > 0.05). However, post-exercise blood [lactate] was significantly greater in BRJ following the 1500 m TT (6.6 ± 1.2 vs. 6.1 ± 1.5 mM; P < 0.05), but not significantly different between conditions in the 10,000 m TT (P > 0.05). Performance in the 1500 m TT was significantly faster in BRJ vs. PLA (319.6 ± 36.2 vs. 325.7 ± 38.8 s; P < 0.05). Conversely, there was no significant difference in 10,000 m TT performance between conditions (2643.1 ± 324. 1 vs. 2649.9 ± 319.8 s, P > 0.05)., Conclusion: Acute BRJ supplementation significantly enhanced 1500 m, but not 10,000 m TT performance. These findings suggest that BRJ might be ergogenic during shorter distance TTs which allow for a high work rate, but not during longer distance TTs, completed at a lower work rate.

Rationale: Nitrate-rich beetroot juice has been shown to improve exercise capacity in heart failure with preserved ejection fraction, but studies using pharmacological preparations of inorganic nitrate are lacking., Objectives: To determine (1) the dose-response effect of potassium nitrate (KNO 3 ) on exercise capacity; (2) the population-specific pharmacokinetic and safety profile of KNO 3 in heart failure with preserved ejection fraction., Methods and Results: We randomized 12 subjects with heart failure with preserved ejection fraction to oral KNO 3 (n=9) or potassium chloride (n=3). Subjects received 6 mmol twice daily during week 1, followed by 6 mmol thrice daily during week 2. Supine cycle ergometry was performed at baseline (visit 1) and after each week (visits 2 and 3). Quality of life was assessed with the Kansas City Cardiomyopathy Questionnaire. The primary efficacy outcome, peak O 2 -uptake, did not significantly improve ( P =0.13). Exploratory outcomes included exercise duration and quality of life. Exercise duration increased significantly with KNO 3 (visit 1: 9.87, 95% confidence interval [CI] 9.31-10.43 minutes; visit 2: 10.73, 95% CI 10.13-11.33 minute; visit 3: 11.61, 95% CI 11.05-12.17 minutes; P =0.002). Improvements in the Kansas City Cardiomyopathy Questionnaire total symptom (visit 1: 58.0, 95% CI 52.5-63.5; visit 2: 66.8, 95% CI 61.3-72.3; visit 3: 70.8, 95% CI 65.3-76.3; P =0.016) and functional status scores (visit 1: 62.2, 95% CI 58.5-66.0; visit 2: 68.6, 95% CI 64.9-72.3; visit 3: 71.1, 95% CI 67.3-74.8; P =0.01) were seen after KNO 3 . Pronounced elevations in trough levels of nitric oxide metabolites occurred with KNO 3 (visit 2: 199.5, 95% CI 98.7-300.2 μmol/L; visit 3: 471.8, 95% CI 377.8-565.8 μmol/L) versus baseline (visit 1: 38.0, 95% CI 0.00-132.0 μmol/L; P <0.001). KNO 3 did not lead to clinically significant hypotension or methemoglobinemia. After 6 mmol of KNO 3 , systolic blood pressure was reduced by a maximum of 17.9 (95% CI -28.3 to -7.6) mm Hg 3.75 hours later. Peak nitric oxide metabolites concentrations were 259.3 (95% CI 176.2-342.4) μmol/L 3.5 hours after ingestion, and the median half-life was 73.0 (interquartile range 33.4-232.0) minutes., Conclusions: KNO 3 is potentially well tolerated and improves exercise duration and quality of life in heart failure with preserved ejection fraction. This study reinforces the efficacy of KNO 3 and suggests that larger randomized trials are warranted., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02256345., (© 2016 American Heart Association, Inc.)

With an aging population, the number of elderly individuals residing in long-term care (LTC) facilities will continue to grow and pose unique challenges to disaster preparedness and response. With this rapidly growing vulnerable population, it becomes imperative to identify enhanced and novel preparedness strategies and measures. LTC residents not only have complicated medical needs, including the timing of dispensing multiple medications, but frequently have cognitive and mobility deficits as well. In nearly every major disaster, elderly populations have suffered disproportionate morbidity and mortality. This is often due to elderly evacuees getting overlooked in the chaos of an initial response. Instituting measures to rapidly recognize this population in a crowd during an evacuation will reduce their risk. This commentary reviews the LTC facility evacuation challenges of the 2013 explosion of the West Fertilizer Company plant in West, Texas, and offers a novel solution of mandating the wearing of pink vests by all nursing home residents in case of an evacuation. The pink vests quickly alert disaster rescue and response workers of LTC residents with special needs. (Disaster Med Public Health Preparedness. 2017;11:28-30).

Objectives: To assess the impact of the Parklife annual music festival on the local hospital, North Manchester General., Methods: Data was obtained retrospectively by analysis of emergency department records during the weekend of Parklife 2015., Results: 32 patients were identified, 56% reported taking drugs. 34% were admitted for overnight observation. 4 patients presented with methaemoglobinaemia following oral ingestion of amyl nitrate. One patient had a methaemoglobin fraction of 90.6%, which is amongst the most extreme recorded in literature., Conclusion: Music festivals can impose a burden on local health services. Organisers should operate an efficient surveillance system in order to prevent the sale and use of recreational drugs, providing adequate on-site health services and working in collaboration with local emergency services.

In this chapter, several factors that should be considered for selecting and developing suitable analytical methods for determining nitrite/nitrate are presented. Nitrite and nitrate occurrence and suitability are a controversial issue. Nitrite is an approved additive considered a foremost curing ingredient for the preservation of meat products. Nitrate is a natural constituent of the human diet that, however, raises fears for its suggested potential harmfulness related to carcinogenesis and environmental contamination. Chemical, regulatory, and analytical aspects are discussed in the light of the need to obtain reliable data of nitrite and nitrate for law enforcement purposes, exposure estimates, and investigation of their physiological role in the human body. In addition, current metrological aspects to ensure the "fitness for purpose" of the selected method are suggested and discussed., (© 2017 Elsevier Inc. All rights reserved.)

Coronary artery disease is the leading cause of mortality in the United States and can result in significant morbidity. In particular, stable ischemic heart disease (SIHD) is a condition that affects nearly 9 million individuals in the United States alone, with substantial annual health care costs related to recurrent medical visits and chronic disease management. Nitrates form a cornerstone of SIHD management by reducing myocardial oxygen consumption and increasing exercise capacity by several mechanisms, including increasing epicardial blood flow through vasodilation and decreased vascular resistance, blunting coronary steal, and reducing preload. Yet the role of nitrates may be underappreciated in clinical practice and their utilization may be limited due to concerns of tolerance to treatment, a lack of randomized data validating their ability to prevent adverse cardiovascular events, and the pervasive use of percutaneous interventions without robust attempts at implementing optimal medical therapy. In this review, we discuss both the recent ACC/AHA/ACP/AATS/PCNA/SCAI/STS and European Society of Cardiology guidelines, with a particular focus on indications, contraindications, and future directions of nitrate therapy in SIHD.

Although the incidence of cardiovascular diseases classically associated with human immunodeficiency virus (HIV) has decreased considerably with antiretroviral therapy, cardiovascular risk, and especially ischemic heart disease, are higher in HIV-infected patients than in uninfected individuals. This is due to the interaction of patient-dependent factors with virus-dependent factors, as well as factors associated with antiretroviral therapy. With increasing of life expectancy and the chronicity of HIV infection, cardiovascular disease has emerged as an important cause of morbidity and mortality in HIV patients. In developed countries, the most common cardiovascular manifestation of HIV is ischemic heart disease. Currently, it is not uncommon to find HIV patients with acute coronary syndrome and, given the important pharmacokinetic interactions of antiretroviral drugs, it is important to know which cardiovascular treatments are safe in this group of patients. The ideal approach would be to mitigate the cardiovascular risk in HIV patients with specific primary prevention measures. All these issues are discussed in this review, which aims to aid clinical cardiologists faced with HIV patients with ischemic heart disease or with high cardiovascular risk in daily clinical practice., (Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

The purpose of this study was to investigate the effects of dietary nitrate supplementation, in the form of beetroot juice, on acute mountain sickness (AMS) symptoms and physiological responses, in a group of young males trekking to Mount Everest Base Camp (EBC). Forty healthy male students (mean age (SD): 16 (1) yrs) trekked to EBC over 11 days. Following an overnight fast, each morning participants completed the Lake Louise AMS questionnaire and underwent a series of physiological tests: resting blood pressure as well as resting and exercising heart rate, respiratory rate, and peripheral oxygen saturation. The exercise test consisted of a standardised 2-min stepping protocol and measurements were taken in the last 10 s. Participants in the intervention arm of the study consumed 140 ml of concentrated beetroot juice daily, containing approximately 10 mmol of nitrate, while those in the control arm consumed 140 ml of concentrated blackcurrant cordial with negligible nitrate content. Drinks were taken for the first seven days at high altitude (days 2-8), in two equal doses; one with breakfast, and one with the evening meal. Mixed modelling revealed no significant between-groups difference in the incidence of AMS (Odds Ratio - nitrate vs., Control: 1.16 (95% CI: 0.59; 2.29)). Physiological changes occurring during ascent to high altitude generally were not significantly different between the two groups (Model Coef (95% CI) - average difference nitrate vs., Control: systolic blood pressure, 0.16 (-4.47; 4.79); peripheral oxygen saturation, 0.28 (-0.85; 1.41); heart rate, -0.48 (-8.47; 7.50) (Model Coef (95% CI) - relative difference nitrate vs., Control: ventilatory rate, 0.95 (0.82; 1.08)). Modelling revealed that diastolic blood pressure was 3.37 mmHg (0.24; 6.49) higher for participants in the beetroot juice, however this difference was no larger than that found at baseline and no interaction effect was observed. Supplementation with dietary nitrate did not significantly change symptoms of AMS or alter key physiological variables, in a group of adolescent males during a high altitude trekking expedition. There was no evidence of harm from dietary nitrate supplementation in this context. Given the wide confidence intervals in all models, a larger sample size would be required to exclude a false negative result. Our data suggest that prolonged oral nitrate supplementation is safe and feasible at altitude but has little physiological or clinical effect., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In the last 60 years dramatically increased the content of nitrates in groundwater due to intensive use of nitrogen fertilizers in agriculture. Research in post-Chernobyl period has shown that a sharp increase in the incidence of thyroid cancer depends not only on the level of thyroid dose, but also on the level of nitrates in groundwater.

Purpose of Review: The purpose of this article is to collect the most recent data regarding the safety of well-known or emerging dietary supplements used by athletes., Recent Findings: From January 2014 to April 2016, about 30 articles have been published in the field. New data show that 90% of sports supplements contain trace of estrogenic endocrine disruptors, with 25% of them having a higher estrogenic activity than acceptable. About 50% of the supplements are contaminated by melamine, a source of nonprotein nitrogen. Additional data accumulate toward the safety of nitrate ingestion. In the last 2 years, the safety of emerging supplements such as higenamine, potentially interesting to lose weight, creatine nitrate and guanidinoacetic acid has been evaluated but still needs further investigation., Summary: The consumption of over-the-counter supplements is very popular in athletes. Although most supplements may be considered as safe when taking at the recommended doses, athletes should be aware of the potential risks linked to the consumption of supplements. In addition to the risks linked to overdosage and cross-effects when combining different supplements at the same time, inadvertent or deliberate contamination with stimulants, estrogenic compounds, diuretics or anabolic agents may occur.

Summarizing paper contains short analysis of the publications resulting cell biological, molecular genetic and population genetic investigations devoted to studying of accute radiation exposure and chronic radiation contamination effects on biological systems after disaster on Chornobyl nuclear power station in 1986.

Several food additives are added in food for their preservation to maintain the freshness of food (antioxidants) or to slow down or stop the growth of microorganisms (preservative agents). Nitrites and nitrates are used as preservative agents in meat. Nitrites give a smoked taste, a pinkish color in the meat and protect the consumers against the risk of bacterial deterioration. Their addition is however very limited as, in high dose, it can have risks on human health and the environment. Nitrites may also combine with secondary or tertiary amines to form N-nitroso derivatives. Certain N-nitroso compounds have been shown to produce cancers in a wide range of laboratory animals. Thus, alternatives of nitrates and nitrites are the object of numerous research studies. Alternatives, such as the addition of vitamins, fruits, chemicals products, natural products containing nitrite or spices, which have similar properties of nitrites, are in evaluation. In fact, spices are considered to have several organoleptic and anti-microbial properties which would be interesting to study. Several spices and combinations of spices are being progressively evaluated. This review discusses the sources of nitrites and nitrates, their use as additives in food products, their physicochemical properties, their negatives effects and the use of alternatives of nitrites and nitrates in preserving meat products.

Consumers have an illogical relationship with nitrite (and its precursor, nitrate) in food. Despite a long history of use, nitrite was nearly banned from use in foods in the 1970s due to health concerns related to the potential for carcinogenic nitrosamine formation. Changes in meat processing methods reduced those potential risks, and nitrite continued to be used in foods. Since then, two opposing movements continue to shape how consumers view dietary nitrate and nitrite. The discovery of the profound physiological importance of nitric oxide led to the realization that dietary nitrate contributes significantly to the nitrogen reservoir for nitric oxide formation. Numerous clinical studies have also demonstrated beneficial effects from dietary nitrate consumption, especially in vascular and metabolic health. However, the latest wave of consumer sentiment against food additives, the clean-label movement, has renewed consumer fear and avoidance of preservatives, including nitrite. Education is necessary but may not be sufficient to resolve this disconnect in consumer perception., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the safety and ocular hypotensive efficacy of 4 trabodenoson doses administered twice daily over 14 or 28 days in subjects with ocular hypertension or primary open-angle glaucoma (POAG)., Methods: In this multicenter, randomized, double-masked, placebo-controlled, dose-escalation Phase 2 study, patients received unilateral topical twice-daily trabodenoson (50, 100, or 200 mcg) or placebo for 14 days, or 500 mcg trabodenoson or placebo for 28 days. Ocular and systemic safety and tolerability were assessed by examinations, clinical and laboratory studies. Intraocular pressure (IOP) was assessed using Goldmann tonometry., Results: Trabodenoson was well tolerated; no clinically meaningful ocular or systemic side effects were identified. Trabodenoson produced a dose-dependent IOP reduction. IOP reductions in the 500 mcg group were significantly greater than placebo at all time points at Day 28. Mean IOP reductions from diurnal baseline ranged from -3.5 to -5.0 mmHg with a mean change of -4.1 mmHg in the 500 mcg group compared -1.0 to -2.5 mmHg with a mean change of -1.6 mmHg for the placebo group, and the Day 28 drop was significantly greater than at Day 14 (P = 0.0163) indicating improvement in IOP lowering with longer treatment time. IOP remained significantly reduced 24 h after the final 500 mcg dose (P = 0.048)., Conclusion: Twice-daily ocular doses of trabodenoson, from 50 to 500 mcg, were well tolerated and showed a dose-related decrease in IOP that was statistically significant and clinically relevant at 500 mcg in patients with ocular hypertension or POAG., Competing Interests: Author Disclosure Statement J.S.M. is a consultant and member of the Inotek Scientific Advisory Board; R.A.B., W.M., and C.C.R. are employees and own stock and stock options of Inotek Pharmaceuticals; N.S. is a consultant; K.N.S. and H.D. have no competing financial interests.

While many studies have investigated the health effects associated with acute exposure to fine particulate matter (particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM2.5)), very few have considered the risks of specific sources of PM2.5 We used city-specific source apportionment in 8 major metropolitan areas in California from 2005-2009 to examine the associations of source-specific PM2.5 exposures from vehicular emissions, biomass burning, soil, and secondary nitrate and sulfate sources with emergency department visits (EDVs) for cardiovascular and respiratory diseases, including 7 subclasses. Using a case-crossover analysis, we observed associations of vehicular emissions with all cardiovascular EDVs (excess risk = 1.6%, 95% confidence interval: 0.9, 2.4 for an interquartile-range increment of 2.8 µg/m(3)) and with several subclasses of disease. In addition, vehicular emissions, biomass burning, and soil sources were associated with all respiratory EDVs and with EDVs for asthma. The soil source, which includes resuspended road dust, generated the highest risk estimate for asthma (excess risk = 4.5%, 95% confidence interval: 1.1, 8.0). Overall, our results provide additional evidence of the public health consequences of exposure to specific sources of PM2.5 and indicate that some sources of PM2.5 may pose higher risks than the overall PM2.5 mass., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Few studies have evaluated environmental chemical exposures in relation to ovarian cancer. We previously found an increased risk of ovarian cancer among postmenopausal women in Iowa associated with higher nitrate levels in public water supplies (PWS). However, elevated nitrate levels may reflect the presence of other agricultural chemicals, such as atrazine, one of the most commonly detected pesticides in Iowa PWS., Methods: We evaluated the association between atrazine in drinking water and incident ovarian cancer (N=145, 1986-2010) among 13 041 postmenopausal women in the Iowa Women's Health Study who used their PWS for ≥11 years as reported in 1989. Average levels of atrazine (1986-1987), nitrate-nitrogen (NO3-N, 1955-1988) and estimated levels of total trihalomethanes (TTHM, 1955-1988) from PWS monitoring data were linked to the participants' cities of residence. We computed HRs and 95% CIs by categories of the average atrazine level (not detected, ≤ or >0.37 parts per billion=median) using Cox proportional hazards regression adjusting for ovarian cancer risk factors., Results: Atrazine was detected in water samples from 69 cities where 4155 women (32%) lived and levels were moderately correlated with NO3-N (ρ=0.35) and TTHM (ρ=0.24). Atrazine levels were not associated with ovarian cancer risk with or without adjusting for NO3-N and TTHM levels (p-trend=0.50 and 0.81, respectively). Further, there was no evidence for effect modification of the atrazine association by NO3-N or TTHM levels., Conclusions: In our study with low atrazine detection rates, we found no association between atrazine in PWS and postmenopausal ovarian cancer risk., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Purpose: There is a lack of knowledge on the effects of nitrates alone in heart failure (HF). We aimed to assess the impact of nitrates use in the occurrence of ischemic events in patients with ischemic HF attending an HF clinic., Methods: We performed a retrospective analysis of a cohort of 632 patients managed in an HF clinic between January 2000 and December 2011. Patients with ischemic etiology were selected (n = 290). Patients were classified according to chronic nitrates use (n = 83 nitrates users vs n = 194) and followed up for 5 years for the occurrence of fatal or nonfatal myocardial infarction or stroke., Results: Nitrates users had more frequently diabetes, dyslipidemia, and higher body mass index but were less frequently treated with statins. Thirty adverse events were recorded (n = 16 in nitrates group). Variables significantly associated with the occurrence of the end point in univariate analysis were arterial hypertension, diabetes, and nitrates use. Male gender, beta-blockers, statin, and clopidogrel use had a protective effect on the occurrence of the end point. In multivariate analysis, nitrates use remained an independent predictor of adverse outcome when adjusted for each of the variables: arterial hypertension, gender, diabetes, beta-blocker, and clopidogrel use; however, when adjusted for statin use, nitrates were no longer associated with the outcome., Conclusion: Long-term nitrates use in patients with ischemic HF was associated with higher occurrence of ischemic events, defined as fatal or nonfatal myocardial infarction or stroke. Our results, although from a retrospective analysis, do not support a role for chronic nitrate use in HF., (© The Author(s) 2016.)

Ingested nitrate leads to the endogenous synthesis of N-nitroso compounds (NOCs), animal carcinogens with limited human evidence. We aimed to evaluate the risk of colorectal cancer (CRC) associated with nitrate exposure in drinking water and diet. A case-control study in Spain and Italy during 2008-2013 was conducted. Hospital-based incident cases and population-based (Spain) or hospital-based (Italy) controls were interviewed on residential history, water consumption since age 18, and dietary information. Long-term waterborne ingested nitrate was derived from routine monitoring records, linked to subjects' residential histories and water consumption habits. Dietary nitrate intake was estimated from food frequency questionnaires and published food composition databases. Odd ratios (OR) were calculated using mixed models with area as random effect, adjusted for CRC risk factors and other covariables. Generalized additive models (GAMs) were used to analyze exposure-response relationships. Interaction with endogenous nitrosation factors and other covariables was also evaluated. In total 1,869 cases and 3,530 controls were analyzed. Average waterborne ingested nitrate ranged from 3.4 to 19.7 mg/day, among areas. OR (95% CIs) of CRC was 1.49 (1.24, 1.78) for >10 versus ≤5 mg/day, overall. Associations were larger among men versus women, and among subjects with high red meat intake. GAMs showed increasing exposure-response relationship among men. Animal-derived dietary nitrate was associated with rectal, but not with colon cancer risk. In conclusion, a positive association between CRC risk and waterborne ingested nitrate is suggested, mainly among subgroups with other risk factors. Heterogeneous effects of nitrate from different sources (water, animal and vegetables) warrant further research., (© 2016 UICC.)

Background: There is growing evidence regarding the potential properties of nitrate-rich foods in development of chronic diseases. In this study, we investigated the association of nitrate-containing vegetables (NCVs) and the risk of chronic kidney disease (CKD)., Methods: We evaluated 1546 eligible adult participants of the Tehran Lipid and Glucose Study (TLGS), at baseline (2006-2008) and again after 3 years (2009-2011). Dietary intake was collected using the validated semi-quantitative food frequency questionnaire. Nitrate-containing vegetables and its categories including high-, medium-, and low-nitrate vegetables were defined. Estimated glomerular filtration rate (eGFR) and CKD were defined. Association between NCVs and CKD in the cross-sectional phase and the predictability of NCVs consumption in CKD occurrence were assessed using multivariable logistic regression models with adjustment for potential confounders., Results: Mean dietary intake of energy-adjusted NCVs was 298.0 ± 177.3 g/day. Highest compared to the lowest tertile of NCVs was accompanied with a significantly lower mean eGFR (76.6 vs. 83.3, mL/min/1.73 m(2), p < 0.001) and a higher prevalence of CKD (21.7 vs. 9.9%, p < 0.001). At baseline, higher intake of high-NCVs was associated with a 48% higher chance of having CKD (OR = 1.48, 95% CI = 1.05-2.13). After 3 years of follow-up, there was no significant association between consumption of total NCVs and its categories with the occurrence of CKD., Conclusion: Considering the lack of association between high-NCVs intakes and the risk of CKD in prospective analysis, additional research is recommended to clarify possible effect of nitrate intakes from vegetables on kidney function.

The pathogenesis of exercise intolerance in patients with heart failure and preserved ejection fraction (HFpEF) is likely multifactorial. In addition to cardiac abnormalities (diastolic dysfunction, abnormal contractile reserve, chronotropic incompetence), several peripheral abnormalities are likely to be involved. These include abnormal pulsatile hemodynamics, abnormal arterial vasodilatory responses to exercise, and abnormal peripheral O2 delivery, extraction, and utilization. The nitrate-nitrite-NO pathway is emerging as a potential target to modify key physiologic abnormalities, including late systolic left ventricular (LV) load from arterial wave reflections (which has deleterious short- and long-term consequences for the LV), arterial vasodilatory reserve, muscle O2 delivery, and skeletal muscle mitochondrial function. In a recently completed randomized trial, the administration of a single dose of exogenous inorganic nitrate has been shown to exert various salutary arterial hemodynamic effects, ultimately leading to enhanced aerobic capacity in patients with HFpEF. These effects have the potential for both immediate improvements in exercise tolerance and for long-term "disease-modifying" effects. In this review, we provide an overview of key mechanistic contributors to exercise intolerance in HFpEF, and of the potential therapeutic role of drugs that target the nitrate-nitrite-NO pathway.

Future climatic changes may have profound impacts on cropping systems and affect the agronomic and environmental sustainability of current N management practices. The objectives of this work were to i) evaluate the ability of the SALUS crop model to reproduce experimental crop yield and soil nitrate dynamics results under different N fertilizer treatments in a farmer's field, ii) use the SALUS model to estimate the impacts of different N fertilizer treatments on NO3- leaching under future climate scenarios generated by twenty nine different global circulation models, and iii) identify the management system that best minimizes NO3- leaching and maximizes yield under projected future climate conditions. A field experiment (maize-triticale rotation) was conducted in a nitrate vulnerable zone on the west coast of Sardinia, Italy to evaluate N management strategies that include urea fertilization (NMIN), conventional fertilization with dairy slurry and urea (CONV), and no fertilization (N0). An ensemble of 29 global circulation models (GCM) was used to simulate different climate scenarios for two Representative Circulation Pathways (RCP6.0 and RCP8.5) and evaluate potential nitrate leaching and biomass production in this region over the next 50 years. Data collected from two growing seasons showed that the SALUS model adequately simulated both nitrate leaching and crop yield, with a relative error that ranged between 0.4% and 13%. Nitrate losses under RCP8.5 were lower than under RCP6.0 only for NMIN. Accordingly, levels of plant N uptake, N use efficiency and biomass production were higher under RCP8.5 than RCP6.0. Simulations under both RCP scenarios indicated that the NMIN treatment demonstrated both the highest biomass production and NO3- losses. The newly proposed best management practice (BMP), developed from crop N uptake data, was identified as the optimal N fertilizer management practice since it minimized NO3- leaching and maximized biomass production over the long term.

The potential associations between dietary consumption of nitrates, nitrites, and nitrosamines and gastric cancer risk have been investigated by several studies, but yielded inconclusive results. We conducted a meta-analysis to provide a quantitative assessment of their relationships. Relevant articles were identified by a systematic literature searching of PubMed and Embase databases prior to August 2015. Random-effects models were employed to pool the relative risks. A total of 22 articles consisting of 49 studies-19 studies for nitrates, 19 studies for nitrites, and 11 studies for N-nitrosodimethylamine (NDMA)-were included. The summary relative risk of stomach cancer for the highest categories, compared with the lowest, was 0.80 (95% confidence interval (CI), 0.69-0.93) for dietary nitrates intake, 1.31 (95% CI, 1.13-1.52) for nitrites, and 1.34 (95% CI, 1.02-1.76) for NDMA (p for heterogeneity was 0.015, 0.013 and <0.001, respectively). The study type was found as the main source of heterogeneity for nitrates and nitrites. The heterogeneity for NDMA could not be eliminated completely through stratified analysis. Although significant associations were all observed in case-control studies, the cohort studies still showed a slight trend. The dose-response analysis indicated similar results as well. High nitrates intake was associated with a weak but statistically significant reduced risk of gastric cancer. Whereas increased consumption of nitrites and NDMA seemed to be risk factors for cancer. Due to the lack of uniformity for exposure assessment across studies, further prospective researches are warranted to verify these findings.

Effluent clarification and disinfection are major challenges in wastewater management. The cladoceran Daphnia magna has been proposed as a cost-effective and ecosystem-friendly option to clarify and disinfect secondary effluents, but its efficacy has not been fully tested under different sewage conditions. The present study explores the effects of temperature and nitrate on the efficacy of D. magna as a tertiary treatment at two different scales (individual assays and microcosms). Individual assays were employed to determine direct effects of temperature and/or nitrate on D. magna cultured in a suspension of organic matter. Using microcosms under the same environmental conditions, we explored the clearing efficacy of D. magna interacting with a natural microbial community. Individual assays revealed that D. magna mortality increased by 17% at 26 °C, 21% at >250 mg NO3(-)/l and by 60% at 26 °C and at >250 mg NO3(-)/l, and individuals displayed reduced body size, filtering rates and fecundity when compared to those at 21 °C and <40 mg NO3(-)/l. Improved performance under these conditions was also mirrored in the microcosms, with a higher density of D. magna (>100 ind/l) at 21 °C and <40 mg NO3(-)/l compared to the number (0-21 ind/l) at 26 °C and/or >250 mg NO3(-)/l. In the microcosms at 21 °C and <40 mg NO3(-)/l, turbidity and the density of bacteria, protists and micro-metazoa decreased in relation to those at 26 °C and/or >250 mg NO3(-)/l. Each treatment developed a unique and characteristic microbial assemblage, and D. magna was identified as the major driver of the community structure of protists and micro-metazoa. This enabled us to determine taxa vulnerability to D. magna grazing, and to re-define their tolerance thresholds for nitrate. In conclusion, this study increases our knowledge of how microbes respond to temperature and nitrate pollution, and highlights that D. magna efficacy as a tertiary treatment can be seriously compromised by variable environmental conditions., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The objective of the study was to investigate the effects of feed consumption rate on potential toxicity, rumen fermentation, and eating behavior when beef heifers were fed a diet supplemented with nitrate (NI). Twelve ruminally cannulated heifers (827 ± 65.5 kg BW) were used in a randomized complete block design. The experiment consisted of 10-d adaptation, 8-d urea-feeding, and 3-d nitrate-feeding periods. All heifers were fed a diet supplemented with urea (UR) during the adaptation and urea-feeding periods, whereas the NI diet (1.09% NO in dietary DM) was fed during the nitrate-feeding period. After adaptation, heifers were randomly assigned to ad libitum or restrictive feeding (about 80% of ad libitum intake) for the urea- and nitrate-feeding periods. Ad libitum DMI decreased (14.1 vs. 15.1 kg/d; < 0.01) when heifers were fed the NI diet compared with the UR diet. The amount of feed consumed increased ( < 0.01) at 0 to 3 h and decreased ( ≤ 0.03) at 3 to 24 h for restrictive vs. ad libitum feeding of both the UR and NI diets. Compared to the UR diet, the NI diet decreased ( < 0.01) feed consumption at 0 to 3 h and increased ( < 0.02) feed consumption at 3 to 24 h (except feed consumption at 9 to 12 h; = 0.90), indicating nitrate feeding changed the consumption pattern (a more even distribution of feed intake over the day). The increased feed consumption from 0 to 3 h after feeding the NI diet restrictively vs. ad libitum numerically decreased ( = 0.11) rumen pH and numerically or significantly increased ( = 0.01 to 0.28) rumen ammonia, NO, and NO; blood methemoglobin; and plasma NO and NO at 3 h. Regression analysis indicated that increased feed consumption (0 to 3 h) exponentially elevated ( < 0.01; = 0.75) blood methemoglobin, and plasma NO + NO among other rumen and blood variables had the greatest correlation (sigmoid response; < 0.01, = 0.47) with feed consumption (0 to 3 h). Particle size distribution of orts was partially altered ( = 0.02 to 0.40) when the NI diet was fed compared with the UR diet. During the nitrate-feeding period, the nitrate content of orts on d 2 and 3 was greater ( = 0.02) than that on d 1. In conclusion, the increased consumption rate of a diet supplemented with nitrate was an important factor influencing risk of nitrate toxicity based on blood methemoglobin and plasma NO. In addition, the pattern of daily feed consumption was altered by nitrate (creating a "nibbling" pattern of eating) in beef heifers.

Acrylates, the 2012 American Contact Dermatitis Society allergen of the year, are found in a range of products including the absorbent materials within feminine hygiene pads. When fully polymerized, acrylates are nonimmunogenic; however, if not completely cured, the monomers can be potent allergens.A 28-year-old woman is presented, who had her teeth varnished with Isodan (Septodont, Saint-Maur-des-Fossés, France) containing HEMA (2-hydroxyethyl methacrylate) with no initial reaction. Approximately 1 month later, the patient developed a genital dermatitis secondary to her feminine hygiene pads. The initial reaction resolved, but 5 months later, the patient developed a systemic contact dermatitis after receiving a second varnishing.The patient was dramatically patch test positive to many acrylates. This case demonstrates a reaction to likely unpolymerized acrylates within a feminine hygiene pad, as well as broad cross-reactivity or cosensitivity to acrylates, and possibly a systemic contact dermatitis with systemic re-exposure to unpolymerized acrylates.

Acute heart failure (AHF) is a growing public health concern with high inhospital mortality and costs. Clinical practice guidelines, underpinned by positive randomized controlled trials, recommend the early use of intravenous (IV) nitrates in the treatment of AHF. However, the "real-world" usage of IV nitrates has not been clearly defined. The objective of this study was to examine the use of IV nitrates in the treatment of AHF as recommended by clinical practice guidelines. A case-record analysis was conducted of all admissions with AHF at a large teaching hospital. Of the 81 AHF patients (mean age 77 ± 11, mean SBP 130 ± 27 mmHg) enrolled for this analysis, only 5 (6%) received IV nitrates at the time of AHF admission. Forty (49%, mean age 77 ± 11, mean SBP 131 ± 27 mmHg) of these 81 patients met the guideline criteria for suitability for IV nitrates and only 5 (12%) of these received them during this admission. Patients who received IV nitrates were more likely to have higher blood pressure and all had myocardial ischemia as a precipitant. Seventy-five (93%) of the total population received loop diuretics on admission. Overall, this study shows that loop diuretics remain the first-line therapy in AHF with little use of IV nitrates, despite recommendations from clinical practice guidelines., (© 2015 John Wiley & Sons Ltd.)

Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds (NOC), potential human carcinogens. We evaluated the association of nitrate and nitrite ingestion with postmenopausal ovarian cancer risk in the Iowa Women's Health Study. Among 28,555 postmenopausal women, we identified 315 incident epithelial ovarian cancers from 1986 to 2010. Dietary nitrate and nitrite intakes were assessed at baseline using food frequency questionnaire data. Drinking water source at home was obtained in a 1989 follow-up survey. Nitrate-nitrogen (NO3 -N) and total trihalomethane (TTHM) levels for Iowa public water utilities were linked to residences and average levels were computed based on each woman's duration at the residence. We computed multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards regression. We tested interactions of nitrate with TTHMs and dietary factors known to influence NOC formation. Ovarian cancer risk was 2.03 times higher (CI = 1.22-3.38, ptrend  = 0.003) in the highest quartile (≥2.98 mg/L) compared with the lowest quartile (≤0.47 mg/L; reference) of NO3 -N in public water, regardless of TTHM levels. Risk among private well users was also elevated (HR = 1.53, CI = 0.93-2.54) compared with the same reference group. Associations were stronger when vitamin C intake was

The potential effects of inorganic nitrate/nitrite on global health are a much debated issue. In addition to possible methemoglobinemia and carcinogenic properties, anti-thyroid effects of nitrate/nitrite have been suggested. Considering the growing significance of nitrate/nitrite and since there is no comprehensive review in data available, clarifying the effect of nitrate/nitrite on thyroid disorder outcomes is essential. Therefore, we conducted this systematic review of experimental and clinical studies, and a meta-analysis of relevant cohort and cross-sectional studies investigating the association of nitrate/nitrite exposure and thyroid function. Most animal studies show that high exposure (~10-600 times of acceptable daily intake) to nitrate/nitrite induces anti-thyroid effects, including decreased serum level of thyroid hormones and histomorphological changes in thyroid gland; however no similar observations have been documented in humans. Based on our meta-analysis, no significant association was observed between nitrate exposure and the risk of thyroid cancer, hyper- and hypothyroidism; findings from three cohort studies however showed a significant association between higher exposure to nitrite and the risk of thyroid cancer (risk = 1.48, 95% confidence interval = 1.09-2.02, P = 0.012). Additional research is needed to clarify the association between nitrate/nitrite exposures and both thyroid function and cancer., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The adverse effects of lead nitrate (LN) and the preventive role of sodium selenite were investigated in diabetic and non-diabetic rat blood by measuring trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP), malondialdehyde (MDA) levels and activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) also by evaluating DNA damage with comet assay. LN increased the levels of MDA, tail DNA%, mean tail length and tail moment, decreased the enzymes activities, FRAP and TEAC values. In sodium selenite+LN group, we observed the protective effect of sodium selenite on examining parameters. Diabetes caused alterations on these parameters, too. We found that sodium selenite did not protect against diabetes caused damages. As a result, LN caused toxic effects on blood cells and sodium selenite alleviated this toxicity but it did not show preventive effect against diabetes. Also, LN caused more harmfull effects in diabetic groups than non-diabetic groups., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Short-term exposure to fine particle mass (PM) has been associated with adverse health effects, but little is known about the relative toxicity of particle components. We conducted a systematic review to quantify the associations between particle components and daily mortality and hospital admissions. Medline, Embase and Web of Knowledge were searched for time series studies of sulphate (SO4(2-)), nitrate (NO3(-)), elemental and organic carbon (EC and OC), particle number concentrations (PNC) and metals indexed to October 2013. A multi-stage sifting process identified eligible studies and effect estimates for meta-analysis. SO4(2-), NO3(-), EC and OC were positively associated with increased all-cause, cardiovascular and respiratory mortality, with the strongest associations observed for carbon: 1.30% (95% CI: 0.17%, 2.43%) increase in all-cause mortality per 1 μg/m(3). For PNC, the majority of associations were positive with confidence intervals that overlapped 0%. For metals, there were insufficient estimates for meta-analysis. There are important gaps in our knowledge of the health effects associated with short-term exposure to particle components, and the literature also lacks sufficient geographical coverage and analyses of cause-specific outcomes. The available evidence suggests, however, that both EC and secondary inorganic aerosols are associated with adverse health effects.

The study aimed to evaluate the effectiveness of in-office bleaching and associated tooth sensitivity on application of nano-calcium phosphate paste as desensitizing agent. Bleaching was performed with 35% hydrogen peroxide gel in 40 patients who were randomly divided into placebo and nano-calcium phosphate paste groups. Bleaching efficacy (BE) was evaluated using a value-oriented Vita shade guide. Tooth sensitivity was recorded using a numeric rating scale (0-4) during bleaching and up to 48 h after each session. The primary outcome of absolute risk of tooth sensitivity was compared using the Fisher's exact test (α = 0.05). The intensity of tooth sensitivity and the efficacy of in-office bleaching were also statistically evaluated. No significant differences in absolute risk and intensity of tooth sensitivity were detected between the groups (p = 1.0 and p = 0.53, respectively). BE was also found to be similar between the groups (p = 0.67). Although the use of a nano-calcium phosphate paste associated with fluoride and potassium nitrate did not influence the whitening outcome, but it also did not reduce bleaching-induced tooth sensitivity.

Nitrate is a natural constituent of the human diet and an approved food additive. It can be partially converted to nitrogen monoxide, which induces vasodilation and thereby decreases blood pressure. This effect is associated with a reduced risk regarding cardiovascular disease, myocardial infarction, and stroke. Moreover, dietary nitrate has been associated with beneficial effects in patients with gastric ulcer, renal failure, or metabolic syndrome. Recent studies indicate that such beneficial health effects due to dietary nitrate may be achievable at intake levels resulting from the daily consumption of nitrate-rich vegetables. N-nitroso compounds are endogenously formed in humans. However, their relevance for human health has not been adequately explored up to now. Nitrate and nitrite are per se not carcinogenic, but under conditions that result in endogenous nitrosation, it cannot be excluded that ingested nitrate and nitrite may lead to an increased cancer risk and may probably be carcinogenic to humans. In this review, the known beneficial and detrimental health effects related to dietary nitrate/nitrite intake are described and the identified gaps in knowledge as well as the research needs required to perform a reliable benefit/risk assessment in terms of long-term human health consequences due to dietary nitrate/nitrite intake are presented., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Many clinically important differences exist between beta blockers. B1-selectivity is of clinical interest because at clinically used doses, b1- selective agents block cardiac b-receptors while having minor effects on bronchial and vascular b-receptors. Beta-adrenergic blocking agents significantly decrease the frequency and duration of angina pectoris, instead the prognostic benefit of beta-blockers in stable angina has been extrapolated from studies of post myocardial infarction but has not yet been documented without left ventricular disfunction or previous myocardial infarction. Organic nitrates are among the oldest drugs, but they still remain a widely used adjuvant in the treatment of symptomatic coronary artery disease. While their efficacy in relieving angina pectoris symptoms in acute settings and in preventing angina before physical or emotional stress is undisputed, the chronic use of nitrates has been associated with potentially important side effects such as tolerance and endothelial dysfunction. B-blockers are the firstline anti-anginal therapy in stable stable angina patients without contraindications, while nitrates are the secondline anti-anginal therapy. Despite 150 years of clinical practice, they remain fascinating drugs, which in a chronic setting still deserve investigation. This review evaluated pharmacotherapy and indications of Beta-blockers and nitrates in stable angina.

Background: Treatment of actinide-contaminated wounds may be problematic because of contaminant physicochemical properties, dissemination and anatomical localization. This study investigates different chelation/resection protocols after contamination of rats with americium (Am) or plutonium (Pu) nitrate or mixed oxide (MOX; uranium (U), Pu oxide)., Methods: Anesthetized rats were contaminated with Am or Pu nitrate (moderately soluble) or MOX (insoluble) following wounding of hind leg muscle. DTPA (diethylene triamine pentaacetic acid) treatment (30 μmol/kg) was immediate or delayed, systemic or local and combined or not with wound resection. Actinide urinary and tissue levels were measured., Results: Comparison of Pu nitrate and MOX dissemination at the wound site indicated a more heterogeneous localization of MOX particles. In all cases DTPA treatment reduced target tissue (bone, liver) activity levels even if DTPA treatment was started 7 days after contamination. Surgery alone increased urinary excretion suggesting release from the wound site but no subsequent increases in organ retention (bone, liver) were observed. The combination of surgery and DTPA increased Pu excretion and reduced tissue levels markedly., Conclusion: This rodent model of actinide wound contamination has been used to test different treatments. It provides evidence of activity release as a result of surgery that seems not to lead to increased organ retention.

Nitrate and nitrite are precursors of endogenously formed N-nitroso compounds (NOC), known animal carcinogens. Nitrosation reactions forming NOCs can be inhibited by vitamin C and other antioxidants. We prospectively investigated the association between dietary nitrate and nitrite intake and risk of colorectal cancer in the Shanghai Women's Health Study, a cohort of 73,118 women ages 40-70 residing in Shanghai. We evaluated effect modification by factors that affect endogenous formation of NOCs: vitamin C (at or above/below median) and red meat intake (at or above/below median). Nitrate, nitrite and other dietary intakes were estimated from a 77-item food frequency questionnaire administered at baseline. Over a mean of 11 years of follow-up, we identified 619 colorectal cancer cases (n = 383, colon; n = 236, rectum). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard regression. Overall, nitrate intake was not associated with colorectal cancer risk (HR = 1.08; 95% CI: 0.73-1.59). However, among women with vitamin C intake below the median (83.9 mg day(-1) ) and hence higher potential exposure to NOCs, risk of colorectal cancer increased with increasing quintiles of nitrate intake (highest vs. lowest quintile HR = 2.45; 95% CI: 1.15-5.18; p trend = 0.02). There was no association among women with higher vitamin C intake. We found no association between nitrite intake and risk of colorectal cancer overall or by intake level of vitamin C. Our findings suggest that high dietary nitrate intake among subgroups expected to have higher exposure to endogenously formed NOCs increases risk of colorectal cancer., (© 2013 UICC.)