The association of dietary nitrates/nitrites intake and the gut microbial metabolite trimethylamine N-oxide and kynurenine in adults: a population-based study.

Background: Dietary nitrate and nitrite may affect the gut microbiota and its metabolites, such as trimethylamine N-oxide (TMAO) and kynurenine (KYN). However, this association and the exact mechanism are still unclear. Therefore, this study aimed to assess the association between dietary consumption of nitrite and nitrate on TMAO and KYN levels in adults. Methods: This cross-sectional study was employed on a subsample baseline phase of the Tehran University of Medical Sciences (TUMS) Employee's Cohort Study (TEC). A total of 250 adults aged 18 years or older were included in the current analysis. Data on the dietary intakes were collected using a validated dish-based food frequency questionnaire (FFQ), and dietary intakes of nitrite and nitrate were estimated using the FFQ with 144 items. Serum profiles and TMAO and KYN were measured using a standard protocol. Results: The findings of this study demonstrate a significant association between the intake of animal sources of nitrate and nitrite and the likelihood of having elevated levels of TMAO and KYN. Specifically, after adjustment, individuals with the highest intake adherence to nitrates from animal sources exhibited increased odds of having the highest level of TMAO (≥51.02 pg/ml) (OR = 1.51, 95% CI = 0.59-3.88, P = 0.03) and KYN (≥417.41 pg/ml) (OR = 1.75, 95% CI = 0.73-4.17, P = 0.02). Additionally, subjects with the highest animal intake from nitrite sources have 1.73 and 1.45 times higher odds of having the highest levels of TMAO and KYN. These results emphasize the potential implications of animal-derived nitrate and nitrite consumption on the levels of TMAO and KYN. Conclusion: The present evidence indicates that a high level of nitrate and nitrite intake from animal sources can increase the odds of high levels of TMAO and KYN. Further studies suggest that we should better evaluate and understand this association.

A Comprehensive Review of Cured Meat Products in the Irish Market: Opportunities for Reformulation and Processing.

Cured meat products constitute one of the meat categories commonly consumed in Ireland and has been part of the Irish cuisine and diet for many years. Ham, gammon, and bacon are some of the products that involve curing as part of the traditional processing methods. Common among these products are high levels of salt and the addition of nitrites. These products undergo processing treatments to create variety, preserve shelf-life, and develop their unique quality and safety characteristics. However, consumers are becoming more conscious of the level of processing involved in these products, and the effects of some components and ingredients might be perceived as unhealthy. Meat product developers have been exploring ways to reduce the amount of ingredients such as salt, saturated fat, and chemical preservatives (e.g., nitrites), which are linked to health concerns. This is a challenging task as these ingredients play an important techno-functional role in the products' quality, safety, and identity. While innovative processing techniques are being introduced and progress has been made in reformulation and packaging technologies, much is still unknown, especially regarding the applicability of many of the proposed interventions to a wide range of meat products and their sustainability at the industrial scale.

Are salivary NO2- / NO2- and NO3- levels biomarkers for dental caries in children? Systematic review and meta-analysis.

The literature is conflicting regarding salivary nitrite (NO2-)/nitrite and nitrate (NO2- and NO3-) levels in children affected by dental caries. For this reason, a systematic review to provide a consensus on the subject was propose, whose objective is to verify whether these molecules could be used as biomarkers in children with caries. A comprehensive search was performed on online database and eleven articles were included in the meta-analysis. The methodological quality of studies was assessed by Newcastle-Ottawa Scale recommended for case-control studies and by AXIS tool for cross-sectional studies. Grading of Recommendations Assessment, Development and Evaluation was used for the assessment of the certainty of the evidence for each outcome. The results showed lower NO2- levels in the group of children affected by dental caries (SMD = -2.18 [-3.24, -1.13], p < 0.01). Age, saliva collection and methods of evaluation can impact the results. When evaluating the severity of the condition, an important variation was detected in relation to the different evaluation methods NO2-/NO2- and NO3-. In conclusion, based on the evidence presented, the results suggest that NO2- levels in saliva are a possible biomarker of dental caries. Results should be evaluated with caution due to the very low evidence from primary studies. Longitudinal studies are necessary to strengthen this hypothesis.

Robust and sensitive determination of nitrites in pickled food by surface-enhanced Raman spectroscopy.

Nitrites are ubiquitous in food and pose a serious threat to human health. Therefore, the rapid and accurate determination of nitrite ion concentration in food is a prerequisite for eliminating the damage of nitrites. In this study, a robust, rapid, and sensitive method is proposed for nitrite detection in pickled food, in which Au@Ag nanoparticles are used as a reliable surface-enhanced Raman spectroscopy (SERS) substrate taking advantage of the high enhancement effect of silver and the good stability of gold. Nitrites were anchored to the surface of the SERS substrate by bridging with 4-aminophenylthiophenol (PATP). With Raman scattering cross-section amplification and internal calibration by PATP, a satisfactory linear relationship (R2 = 0.987) was established for nitrite detection in the concentration range of 5.00-100.00 µM, and the limit of detection (LOD) was 0.17 µM. This SERS-based method demonstrated high selectivity, good precision (RSD < 7.00 %), and satisfying recovery rates (101.42-107.35 %) in real samples, thus improving the determination method for nitrites. Therefore, this method has application potential in food safety and supervision.

Nitrites: An Old Poison or a Current Hazard? Epidemiology of Intoxications Covering the Last 100 Years and Evaluation of Analytical Methods.

In recent times, there has been a concerning and noteworthy rise in the global use of sodium nitrite for suicidal purposes. This is facilitated either through the employment of specialized "suicide kits" or by acquiring sodium nitrite through alternative means. Additionally, another occurrence contributing to nitrite poisoning is the recreational utilization of nitrites in the form of volatile aliphatic esters of nitrous acid, commonly referred to as "poppers". Based on current available papers and reports on the subject of nitrates, nitrites, and poppers intoxications, an epidemiological analysis and evaluation of analytical methods were performed. A total of 128 papers, documenting a collective count of 492 intoxication cases, were identified. Additionally, in order to complete the epidemiological profile of nitrite poisoning, the authors briefly examined six cases of nitrite intoxication that were under investigation in our laboratory. Furthermore, a review of nitrite poisoning cases over the past 100 years shows that the old poison is still in use and poses a substantial risk to society.

Are Chokeberry Products Safe for Health? Evaluation of the Content of Contaminants and Health Risk.

The health-promoting properties of chokeberry fruit have been confirmed in numerous scientific studies. It has been shown that the consumption of these fruits, due to the high content of bioactive compounds, has beneficial effects in neurodegenerative diseases, in addition to having hypolipemic, hypotensive, hypoglycemic, and anti-inflammatory properties. However, different conditions and methods of fruit cultivation, as well as methods of juice and fiber production, may result in a high content of toxic substances, which reduce the health value of chokeberry products. Many substances are environmental pollutants. In this study, for the first time, we examined the content of toxic elements (As, Hg, Cd, Pb), nitrates, and nitrites in all chokeberry juices (organic, conventional, from concentrate, and not from fruit concentrate) without additives and in all chokeberry fibers available in Poland. In addition, risk indicators of adverse health effects were calculated. The median content of the contaminants tested in juices was 0.461 µg/kg for As, 1.170 µg/kg for Cd, 0.427 µg/kg for Hg, 1.404 µg/kg for Pb, 4.892 mg/kg for NO2-, and 41.788 mg/kg for NO3-. These values did not exceed the permissible standards for the calculated indicators. There were also no statistically significant differences in the content of Cd, Hg, and Pb, as well as nitrates (III) and nitrates (V), in the tested juices depending on the method of cultivation and juice production. However, statistically significant differences in As content were found between juices from conventional and organic cultivation (1.032 µg/kg vs. 0.458 µg/kg) and juices from concentrate and not from concentrate (1.164 µg/kg vs. 0.460 µg/kg). There were no statistically significant differences with respect to impurities in fibers. It is shown that the consumption of chokeberry juice and fiber in the amount normally consumed does not pose a health risk associated with the intake of toxic substances; in the case of long-term fiber consumption, the Pb content should be monitored. In particular, organic juices and those not from fruit concentrate are recommended due to the lower As content.

The correlation among residual nitrites, biogenic amines, N-nitrosamine formation, and degradation occurrence of punicalagin α/ß, rosmarinic acid, carnosol, and carnosic acid in extract-treated sausage during storage.

The aim of this study was to investigate the relation between residual α- and ß-punicalagin in Punica granatum L.; PPE and rosmarinic acid, carnosol, and carnosic acid in Salvia eremophila (SE) with residual nitrites, biogenic amines (cadaverine, putrescine, and histamine), N-nitrosodimethylamine (NDMA), microbial counts, lipid oxidation indices, and color values in extract-treated sausage over 14 days of storage. Sausage containing SE + nitrite 60 ppm (SSN) showed minimum levels of the residual nitrites (13.14 mg/kg), NDMA (0.74 ± 0.05 µg/kg), and biogenic amine (histamine, 1.8 mg/kg; cadaverine, 3.7 mg/kg; and putrescine, 4.3 mg/kg) due to retarded degradation rate of 285.84-216.44 mg/kg; rosmarinic acid, 41.62-33.16 mg/kg; carnosol, and 88.70-76.73 mg/kg; carnosic acid over storage time. The first-order kinetic model fitted well for the degradation of rosmarinic acid and carnosol acid in SSN sample. TBA value remained below the threshold limit (0.32 mg kg-1) through 14 days for SSN. Second-order and zero-order reaction models had the best agreement with sausages' PV and TBA values, respectively. After 2 weeks of storage, E. coli and Cl. perfringens counts in the SN120 (sausage containing 120 ppm nitrite) and SSN were significantly lower than the other samples (p < .05), with the values 2.1 and 1.5 log cfu/g for SN120 and 2.2 and 1.6 log cfu/g for SSN formulation. Conversely, oxidation indices, residual nitrites, NDMA, and biogenic amine increased in sausage samples containing PPE extracts (SPN) owing to total degradation of α- and ß-punicalagin during storage. The results indicated that SE can be used as potential co-preservative by reducing the levels of required nitrite in food industry.

Altered Oral Nitrate Reduction and Bacterial Profiles in Hypertensive Women Predict Blood Pressure Lowering Following Acute Dietary Nitrate Supplementation.

BACKGROUND: The efficacy of dietary nitrate supplementation to lower blood pressure (BP) in pregnant women is highly variable. We aimed to investigate whether differences in oral microbiota profiles and oral nitrate-reducing capacity may explain interindividual differences in BP lowering following nitrate supplementation. METHODS: Participants recruited for this study were both pregnant and nonpregnant women, with or without hypertension (n=55). Following an overnight fast, plasma, saliva, and tongue scraping samples were collected for measurement of nitrate/nitrite concentrations, oral NaR (nitrate reductase) activity, and microbiota profiling using 16S rRNA gene sequencing. Baseline BP was measured, followed by the administration of a single dose of dietary nitrate (400 mg nitrate in 70 mL beetroot juice). Post-nitrate intervention, plasma and salivary nitrate/nitrite concentrations and BP were determined 2.5 hours later. RESULTS: Women with hypertension had significantly lower salivary nitrite concentrations (P=0.006) and reduced abundance of the nitrate-reducing taxa Veillonella(P=0.007) compared with normotensive women. Oral NaR activity was not significantly different in pregnant versus nonpregnant women (P=0.991) but tended to be lower in hypertensive compared with normotensive women (P=0.099). Oral NaR activity was associated with both baseline diastolic BP (P=0.050) and change in diastolic BP following acute nitrate intake (P=0.01, adjusted for baseline BP). CONCLUSIONS: The abundance and activity of oral nitrate-reducing bacteria impact both baseline BP as well as the ability of dietary nitrate supplementation to lower BP. Strategies to increase oral nitrate-reducing capacity could lower BP and enhance the efficacy of dietary nitrate supplementation, in pregnancy as well as in nonpregnant adults. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03930693.

Novel Approaches to Improve Meat Products' Healthy Characteristics: A Review on Lipids, Salts, and Nitrites.

Meat products are a staple of many diets around the world, but they have been subject to criticism due to their potential negative impact on human health. In recent years, there has been a growing interest in developing novel approaches to improve the healthy characteristics of meat products, with a particular focus on reducing the levels of harmful salts, lipids, and nitrites. This review aims to provide an overview of the latest research on the various methods being developed to address these issues, including the use of alternative salts, lipid-reducing techniques, and natural nitrite alternatives. By exploring these innovative approaches, we can gain a better understanding of the potential for improving the nutritional value of meat products, while also meeting the demands of consumers who are increasingly concerned about their health and well-being.

Evaluation of the diagnostic performance of the urine dipstick test for the detection of urinary tract infections in patients treated in Kenyan hospitals.

Introduction: Culture is the gold-standard diagnosis for urinary tract infections (UTIs). However, most hospitals in low-resource countries lack adequately equipped laboratories and relevant expertise to perform culture and, therefore, rely heavily on dipstick tests for UTI diagnosis. Research gap: In many Kenyan hospitals, routine evaluations are rarely done to assess the accuracy of popular screening tests such as the dipstick test. As such, there is a substantial risk of misdiagnosis emanating from inaccuracy in proxy screening tests. This may result in misuse, under-use or over-use of antimicrobials. Aim: The present study aimed to assess the accuracy of the urine dipstick test as a proxy for the diagnosis of UTIs in selected Kenyan hospitals. Methods: A hospital-based cross-sectional method was used. The utility of dipstick in the diagnosis of UTIs was assessed using midstream urine against culture as the gold standard. Results: The dipstick test predicted 1416 positive UTIs, but only 1027 were confirmed positive by culture, translating to a prevalence of 54.1 %. The sensitivity of the dipstick test was better when leucocytes and nitrite tests were combined (63.1 %) than when the two tests were separate (62.6 and 50.7 %, respectively). Similarly, the two tests combined had a better positive predictive value (87.0 %) than either test alone. The nitrite test had the best specificity (89.8 %) and negative predictive value (97.4 %) than leucocytes esterase (L.E) or both tests combined. In addition, sensitivity in samples from inpatients (69.2 %) was higher than from outpatients (62.7 %). Furthermore, the dipstick test had a better sensitivity and positive predictive value among female (66.0 and 88.6 %) than male patients (44.3 and 73.9 %). Among the various patient age groups, the dipstick test's sensitivity and positive predictive value were exceptionally high in patients ≥75 years old (87.5 and 93.3 %). Conclusion: Discrepancies in prevalence from the urine dipstick test and culture, the gold standard, indicate dipstick test inadequacy for accurate UTI diagnosis. The finding also demonstrates the need for urine culture for accurate UTI diagnosis. However, considering it is not always possible to perform a culture, especially in low-resource settings, future studies are needed to combine specific UTI symptoms and dipstick results to assess possible increases in the test's sensitivity. There is also a need to develop readily available and affordable algorithms that can detect UTIs where culture is not available.

Exposure to Phosphates and Nitrites through Meat Products: Estimation of the Potential Risk to Pregnant Women.

Diet during pregnancy is one of the most important nutritional challenges associated with some risks for the mother and the fetus. For the first time, the study aims to estimate long-term (2018-2022) exposure to nitrate and phosphates in Serbian pregnant women, based on individual consumption data and accurate values measured in frequently consumed meat products. For this purpose, seven types of meat products, consisting of 3047 and 1943 samples, were collected from retail markets across Serbia, to analyze nitrites and phosphorus content, respectively. These data were combined with meat product consumption data from the Serbian National Food Consumption Survey to assess dietary intake of nitrites and phosphate. The results were compared with the acceptable daily intake (ADI) proposed by the European Food Safety Authority. The average dietary exposure (EDI) to phosphorus ranged from 0.733 mg/kg bw/day (liver sausage and pate) to 2.441 mg/kg bw/day (finely minced cooked sausages). Considering nitrite intake, the major sources were bacon (0.030 mg/kg bw/day) and coarsely minced cooked sausages (0.0189 mg/kg bw/day). In our study, average nitrite and phosphorus exposure in the Serbian pregnant women population are far below the EFSA recommendations (ADI 0.07 mg/kg bw/day and 40 mg/kg bw/day, respectively).

Prevalence of Enterococcal Urinary Tract Infections With Positive Nitrites in Urinalysis in Pediatric Patients With High-Risk for Enterococcal Infections.

Enterococcus is a relatively uncommon pathogen that causes urinary tract infections (UTIs) in healthy children. Most enterococcal infections occur in patients with risk factors such as anatomical or functional urinary tract anomalies, also known as CAKUT (congenital anomalies of kidney and urinary tract). Children who are suspected of having UTIs and who have certain risk factors are often treated specifically for enterococcal infection as part of their empiric regimen. Our primary objective was to determine the prevalence of enterococcal UTIs among high-risk children, and specifically among those with positive nitrite tests, with the goal of avoiding treatment with specific anti-enterococcal agents. This retrospective study included all the episodes of UTI treated at a tertiary pediatric center during 2010 to 2018. The data collected from medical records included nephrological and urological risk factors, nitrite status, and isolated pathogens. Of 931 episodes of UTI, 467 (50%) were considered high-risk. In all, 24 of the latter had Enterococcus as a single pathogen; 23 (96%) of these occurred in patients with negative nitrites in the first urine dipstick taken. The sole patient with high-risk factors, a positive nitrite test and coexisting enterococcal UTI had a history of previous enterococcal UTIs. In pediatric patients with nephrological and urological risk factors, who have positive nitrites in urinalysis, the risk for enterococcal UTI appears substantially low. Therefore, in this context, specific anti-enterococcal empirical antibiotic therapy may be unnecessary.

The Clinical Assessment and Treatment of Inhalant Abuse.

Although inhalant abuse is common, it is one of the most neglected and overlooked forms of substance abuse. Inhalants refer to a wide variety of substances including volatile solvents, aerosols, gases, and nitrites. The mechanism of action of inhalants has not been fully defined. Several molecular targets contribute to the pharmacology, including ion-channel proteins that control neuronal excitability. These agents interact with various receptors and can cause changes in cell-membrane fluidity and nerve-membrane ion channels. Three main pharmacologic categories of inhalants, namely, volatile solvents and anesthetic gases, nitrous oxide, and volatile alkyl nitrites, have distinct pharmacologies, mechanisms of action, and toxicities. Inhalants are linked to multisystem damage affecting the pulmonary, cardiac, dermatologic, renal, hematologic, gastrointestinal, hepatic, and neurologic systems. Chronic inhalant abuse can also cause psychiatric, cognitive, behavioral, and anatomical deficits in humans, leading to reduced productivity and quality of life. Inhalant abuse during pregnancy is associated with fetal abnormalities. Clinical assessment for inhalant abuse should be done systematically. After decontamination and stabilization of the patient, further history and physical examination is necessary to establish an appropriate diagnosis based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Laboratory testing for inhalant abuse is very limited, and imaging studies may be helpful in certain situations. The treatment of inhalant use disorder is similar to that of other substance abuse disorders and includes supportive care, pharmacotherapy, and behavioral therapy. Preventive measures are essential.

Cationic Polystyrene-Based Hydrogels: Low-Cost and Regenerable Adsorbents to Electrostatically Remove Nitrites from Water.

Nitrites are metastable anions that are derived from the oxidation of ammonia by agricultural pollution, sewage, decaying protein, and other nitrogen sources. They are a recognized environmental issue due to their role in eutrophication, as well as in surface and groundwater contamination, being toxic to almost all living creatures. Recently, we reported on the high efficiency of two cationic resins (R1 and R2) forming hydrogels (R1HG and R2HG) by dispersion in water in removing anionic dyes from water by electrostatic binding. Here, aiming at developing adsorbent materials for nitrite remediation, R1, R2, R1HG, and R2HG were first tested in adsorption experiments in batches monitored by UV-Vis methods, using the Griess reagent system (GRS) in order to assess their removal efficiency by contact over time. Particularly, samples of water appositely contaminated with nitrites were analyzed by UV-Vis before and during treatment with the hydrogels. The initial concentration of nitrites was quantified (118 mg/L). Then, the removal of nitrites over time, the removal efficiency of R1HG (89.2%) and of R2HG (89.6%), their maximum adsorption (21.0 mg/g and 23.5 mg/g), as well as the adsorption kinetics and mechanisms were evaluated. Additionally, R1HG- and R2HG-based columns (h = 8-10 cm, ØE = 2 cm) mimicking mini-scale decontamination systems by filtration were used to rapidly filter samples of water polluted with nitrite that were under pressure. R1HG and R2GH were capable of totally removing nitrites (99.5% and 100%) from volumes of nitrite solutions that were 118 mg/L that is 10 times the volumes of resins used. Additionally, when extending filtration to increasing volumes of the same nitrite solution up to 60 times the volume of resins used, the removal efficiently of R1HG decreased, and that of R2HG remained stable at over 89%. Interestingly, both the worn-out hydrogels were regenerable by 1% HCl washing, without a significant reduction in their original efficiency. There is a lack of studies in the literature reporting on novel methods to remove nitrite from water. R1HG and especially R2HG represent low-cost, up-scalable, and regenerable column-packing materials with promise for applications in the treatment of drinking water contaminated by nitrites.

Applicability of the probiotic Lactiplantibacillus plantarum BFL as an adjunct culture in a dry fermented sausage.

The addition of probiotic bacteria to a meat batter allows the development of functional fermented sausages. The aim of this work was to study the effect of microencapsulated Lactiplantibacillus plantarum BFL (EP) and as free cells (FP) on microbiological, physicochemical, and sensory parameters of fermented sausages during the drying stage and on the product ready for consumption. The microencapsulation of L. plantarum BFL did not improve its viability during the drying stage. In addition, sausages inoculated with L. plantarum BFL (FP and EP) caused lower residual nitrites values, pH values and Escherichia coli counts than the Control (C). However, only the presence of free cells of L. plantarum BFL (FP) caused a decrease in the Enterobacteriaceae and mannitol salt-positive Staphylococcus counts. In the sensory analysis, no significant differences were found in the acceptability of the different sausages. However, the acidity in probiotic sausages (FP and EP) was an attribute that consumers highlighted. The probiotic L. plantarum BFL could adapt and survive at high doses in the matrix of an industrial fermented sausage. Therefore, its use could represent a strategy both for biocontrol of pathogens and for the development of functional meat products.

Defining and measuring 'inhalant' use in population-based surveys.

BACKGROUND: The term 'inhalants' is commonly used to describe a group of drugs that are characterised by the route of administration. There are three main sub-groups of inhalants; volatile solvents, alkyl nitrites, and nitrous oxide. These drugs all have different pharmacological properties, use patterns, and potential harms; yet they are sometimes grouped together in survey instruments. This critical review aimed to present a comparative analysis of how these inhalant drugs are defined, and use measured, across a range of population-level drug use surveys. METHODS: Population-level drug use surveys of youth (n=5) and general population (n=6), which measured use of at least once type of inhalant drug, were analysed as case studies. The types of inhalants surveyed were extracted, as well as definitions of these drugs, from code books or survey methods. RESULTS: Differing definitions were used between surveys, and included differences between countries, and between surveys intended to measure youth and general population drug use. Of the six general population surveys; five reported nitrous oxide use, five reported volatile solvent use, and four reported alkyl nitrite use. Of the five youth-specific surveys; three reported volatile solvent use, whereas only one reported on alkyl nitrite use, and one reported nitrous oxide use. CONCLUSIONS: There is no consistent approach used to define or measure the use of inhalant drugs, which has implications for global comparisons and understanding drug use in different populations. We conclude that the term 'inhalants' should be discontinued, due to the limited value in continuing to group very different types of drugs solely on the basis of their route of administration. Improving the epidemiology of volatile solvents, alkyl nitrites, and nitrous oxide as distinct drug types will be of benefit to harm reduction, treatment, and prevention efforts, and ensure these are targeted appropriately to population groups and context of use.

Intoxicación suicida por nitrito sódico: una peligrosa modalidad en Internet. A propósito de un caso / Suicidal poisoning by sodium nitrite: A dangerous mode from Internet. In regard of a case

Se reporta un caso de suicidio por ingesta de nitritos. Se trata de una joven que fue hallada muerta en un vehículo junto a una serie de objetos, entre ellos una bolsa de polvo blanco etiquetada como «nitrito sódico» y comprimidos de lorazepam, paracetamol y metoclopramida. La autopsia reveló signos compatibles con metahemoglobinemia. Se remitieron muestras de sangre, humor vítreo y contenido gástrico, así como la bolsa con el polvo, los comprimidos y otros objetos al Servicio de Drogas del Departamento de Madrid del Instituto Nacional de Toxicología y Ciencias Forenses. El polvo fue identificado como nitrito sódico, y se detectaron concentraciones de nitritos en las muestras biológicas similares a las de otras intoxicaciones letales. El porcentaje de metahemoglobina en sangre fue del 80%. La existencia de páginas en Internet donde el suicidio con nitritos y metoclopramida es detalladamente descrito, así como el aumento del reporte de este tipo de suicidios, alertan acerca de una posible tendencia. (AU)

A case of suicide by nitrites ingestion is reported: a young woman was found death into a car with various objetcs around her, such as a white powder bag labelled as «sodium nitrite» and pills of lorazepam, acetaminophen and metoclopramide. The autopsy revealed signs compatible with methemoglobinemia and samples of blood, vitreous and gastric content were submitted to the Drugs Service of the National Institute of Toxicology and Forensic Sciences in Madrid, as well as the powder bag, the pills and other objects. The white powder was identified as sodium nitrite, and nitrites concentrations similar to other fatalities were detected in biological samples. The methemoglobin level was 80%. The existence of websites where suicide with nitrites and metoclopramide is described step-by-step, joined to the increasement of reports about these fatalities, alert us to a possible trend. (AU)

Nitrosated Active Pharmaceutical Ingredients - Lessons Learned?

The occurrence of N-nitrosodialkylamines in active pharmaceutical ingredients (APIs) and drug products in the last years was a kind of eye opener with regard to quality of drugs. We became aware of the fact that quality control tests described in the international pharmacopoeias might not be sufficient. The N-nitrosodialkylamines found were neither so-called (structurally) related substances, nor residual solvents or heavy metals; hence they were not limited by a compendial test, but by the ICH guideline M7 of mutagenic impurities. Additionally, nitrosamine drug-substance-related impurities (NDSRIs) were detected, mostly within the process of risk assessment required by regulatory authorities. Here, the APIs containing a vulnerable amino moiety had reacted with nitrites being a contaminant of an excipient. This review deals with the formation, toxicity, and mitigation of NDSRISs.

(Poly)phenols and nitrolipids: Relevant participants in nitric oxide metabolism.

Nitric oxide (•NO) is an essential molecule able to control and regulate many biological functions. Additionally, •NO bears a potential toxicity or damaging effects under conditions of uncontrolled production, and because of its participation in redox-sensitive pathways and oxidizing reactions. Several plant (poly)phenols present in the diet are able to regulate the enzymes producing •NO (NOSs). In addition, (poly)phenols are implicated in defining •NO bioavailability, especially by regulating NADPH oxidases (NOXs), and the subsequent generation of superoxide and •NO depletion. Nitrolipids are compounds that are present in animal tissues because of dietary consumption, e.g. of olive oil, and/or as result of endogenous production. This endogenous production of nitrolipids is dependent on the nitrate/nitrite presence in the diet. Select nitrolipids, e.g. the nitroalkenes, are able to exert •NO-like signaling actions, and act as •NO reservoirs, becoming relevant for systemic •NO bioavailability. Furthermore, the presence of (poly)phenols in the stomach reduces dietary nitrite to •NO favoring nitrolipids formation. In this review we focus on the capacity of molecules representing these two groups of bioactives, i.e. (poly)phenols and nitrolipids, as relevant participants in •NO metabolism and bioavailability. This participation acquires especial relevance when human homeostasis is lost, for example under inflammatory conditions, in which the protective actions of (poly)phenols and/or nitrolipids have been associated with local and systemic •NO bioavailability.

Ventricular fibrillation in a 21-year-old after inhalation of an isobutyl nitrite "popper" product.

BACKGROUND: Alkyl nitrite analogs known as "poppers" have been inhaled recreationally for decades. They are available to be purchased from gas stations marketed as "nail polish remover not for human consumption". These rapid-onset, short-acting, vasodilators cause the user to experience euphoria, dizziness, tachycardia and flushing. While chronic use may lead to problems such as methemoglobinemia or neuropathy, nitrites rarely lead to acute life-threatening side effects such as ventricular dysrhythmias. CASE REPORT: We report a case of ventricular fibrillation cardiac arrest in a 21-year-old male after inhaling from a solution labeled to contain isobutyl nitrite, a rarely reported adverse effect of "popper" use. The product was analytically confirmed to contain mainly isobutyl alcohol, volatile hydrocarbons, and isobutyl nitrite, as well as smaller quantities of other substances. The patient was also prescribed escitalopram and hydroxyzine may have contributed. Return of spontaneous circulation was achieved in the field after initiation of CPR and defibrillation. He was found to have no clear predisposition to arrythmias during his care or on follow up. CONCLUSION: Alkyl nitrite "popper" users and clinicians should be aware that products labeled to contain nitrites may contain volatile hydrocarbons along with nitrites and have the potential to cause arrhythmia.