Comparing Confirmed Sodium Nitrite Suicide Deaths With Poison Center Surveillance Estimates.

Importance: Sodium nitrite is a curing agent increasingly used for self-harm and suicide, and multiple locales have reported increasing cases. However, approaches to forensic investigation of these cases are not standardized, and current modes of surveillance in the United States may be inadequate. Objective: To define a potential standard approach for identifying sodium nitrite deaths based on forensic confirmation, and compare findings based on this standard to poison center surveillance. Design, Setting, and Participants: This retrospective case series of sodium nitrite exposures and deaths was conducted in 2 urban medical examiner jurisdictions in New York State from 2000 to 2022. The population-based sample included individuals from (1) medical examiner reports of decedents where the cause of death was sodium nitrite and (2) poison center reports of intentional exposures to sodium nitrite. Exposure: Sodium nitrite as either cause of death (medical examiner reports) or intentional exposure (poison center reports). Main Outcomes and Measures: Medical examiner determination of sodium nitrite deaths was considered the criterion standard and relied largely on confirmatory blood nitrite testing. Poison center records were assessed for intentional exposures to sodium nitrite. Results: In this case series of 36 decendents, median (range) age was 28 (20-57) years; 23 (63.8%) were male; 6 (16.7%) were African-American, 5 (13.9%) were Chinese, 13 (36.1%) were White, and 4 (11.1%) had unknown race; and 6 (16.7%) were Hispanic. No deaths were found from 2000 to 2018, and yearly increases in deaths from 2019 to 2022; these deaths were largely missed by local poison center surveillance. Most cases (83.3% [n = 30]) had postmortem blood nitrite concentrations available, and multiple decedents had evidence of suicide kit recommendations from internet sources. Conclusions and Relevance: In this case series of decedents in 2 New York medical examiner jurisdictions, sodium nitrite deaths increased yearly, and the medical examiners were able to obtain confirmatory nitrite concentrations in most cases. These findings suggest that poison center surveillance underestimates confirmed deaths from sodium nitrite; public health authorities should rely on multiple data sources when analyzing this problem, and forensic analyses should be standardized.

Metabolic reprogramming of corn oligopeptide in regulating sodium nitrite-induced canine hepatocyte injury via TGF/NF-κB signaling pathways and aminoacyl-tRNA biosynthesis.

Sodium nitrite (SN), a prevalent food preservative, is known to precipitate hepatotoxicity upon exposure. This study elucidates the hepatoprotective effects of corn oligopeptide (COP) and vitamin E (VE) against SN-induced hepatic injury in canine hepatocytes. Canine liver cells were subjected to SN to induce hepatotoxicity, followed by treatment with COP and VE. Evaluations included assays for cell viability, oxidative stress markers, apoptosis, and inflammatory cytokines. Additionally, transcriptomic and metabolomic analyses were performed to delineate the underlying molecular mechanisms. The findings demonstrated that COP and VE significantly ameliorated SN-induced cytotoxicity, oxidative stress, and apoptosis. It was evidenced by restored cell viability, enhanced antioxidant enzyme activity, reduced cytoplasmic enzyme leakage, and decreased levels of malondialdehyde and inflammatory cytokines, with COP showing superior efficacy. The RNA sequencing revealed that COP treatment suppressed the SN-activated aminoacyl-tRNA biosynthesis pathway and TGF-ß/NF-κB signaling pathways, thereby mitigating amino acid depletion, apoptosis, and inflammation. Moreover, COP treatment upregulated genes associated with protein folding, bile acid synthesis, and DNA repair. Metabolomic analysis corroborated these results, showing that COP restored amino acid levels and enhanced bile acid metabolism, alleviating SN-induced metabolic disruptions. These findings offered significant insights into the protective mechanisms of COP underscoring its prospective application in treating liver injuries.

The hemodynamic response to nitrite is acute and dependent upon tissue perfusion.

In the vasculature, nitric oxide (NO) is produced in the endothelium by endothelial nitric oxide synthase (eNOS) and is critical for the regulation of blood flow and blood pressure. Blood flow may also be regulated by the formation of nitrite-derived NO catalyzed by hemoproteins under hypoxic conditions. We sought to investigate whether nitrite administration may affect tissue perfusion and systemic hemodynamics in WT and eNOS knockout mice. We found that global eNOS KO mice show decreased tissue perfusion compared to WT mice by using laser speckle contrast imaging. To study both the acute and long-term effects of sodium nitrite (0, 0.1, 1, and 10 mg/kg) on peripheral blood flow and systemic blood pressure, a bolus of nitrite was delivered intraperitoneally every 24 h over 4 consecutive days. We found that nitrite administration resulted in a dose-dependent and acute increase in peripheral blood flow in eNOS KO mice but had no effects in WT mice. The nitrite induced changes in tissue perfusion were transient, as determined by intraindividual comparisons of tissue perfusion 24-h after injection. Accordingly, 10 mg/kg sodium nitrite acutely decreased blood pressure in eNOS KO mice but not in WT mice as determined by invasive Millar catheterization. Interestingly, we found the vasodilatory effects of nitrite to be inversely correlated to baseline tissue perfusion. These results demonstrate the nitrite acutely recovers hypoperfusion and hypertension in global eNOS KO mice and suggest the vasodilatory actions of nitrite are dependent upon tissue hypoperfusion.

Redox-Active Compounds in the Therapy of Drug-Resistant Murine Leukemia P388 Strains.

The efficiency of combinations of cytostatics cisplatin and adriamycin with antioxidant sodium 3-(3'-tert-butyl-4-hydroxyphenyl)propyl thiosulfate (TS-13), and nitric oxide (NO) donor NaNO2 was evaluated on two drug-resistant strains of leukemia P388 with changed redox-status of cells. Simultaneous use of both NO donor and TS-13 in combinations with the cytostatics did not increase the efficiency of therapy. In addition, antioxidant activity of TS-13, NaNO2, and their combinations was studied by the method of luminol-dependent chemiluminescence on the model systems with the use of the homogenized cells of sensitive strain and two drug-resistant strains of leukemia P388. It was shown that TS-13 and NO donor produced opposite effects: TS-13 decreased, while NO donor increased the content of free radicals in the model system. Combinations of antioxidant TS-13 and NO donor should be used with consideration for the redox-status of tumor treated.

Impact of chlorogenic acid on submandibular salivary gland and liver of albino rats exposed to sodium nitrite.

AIM: The aim of the present study is to show how sodium nitrite alters the histology of submandibular salivary glands and livers of Albino rats, as well as how chlorogenic acid may have therapeutic benefits. METHODS: A sample size of thirty male Sprague Dawley Albino rats weighing between 100 and 150 g (5-6 weeks old) was randomly allocated into 3 equal groups. Group I: rats were used as controls and were given phosphate buffer solution, whereas Group II: rats were given an 80 mg/kg sodium nitrites (SN) daily dissolved in distilled water. The rats in Group III were given a daily dose of 80 mg/kg SN dissolved in distilled water and after 6 hours each rat received 50 mg/mL freshly prepared chlorogenic acid (CGA) every other day. For 12 weeks, all treatment modalities will be administered orally, every day. After the experiment, all rats were euthanized. Samples from salivary glands and livers were processed and stained with H&E and interleukin 6 (IL 6). Malondialdehyde (MDA) and superoxide dismutase (SOD) enzymes were detected using an ELISA assay. RESULTS: Groups III had nearly comparable findings to Group I regarding histological pattern with normal submandibular glands and livers features. Group III salivary gland treated with CGA exhibited higher SOD levels (20.60±4.81 U/g) in comparison to the SN group, and lower MDA levels (111.58±28.28 nmol/mg) in comparison to the SN treated samples. In comparison to the SN group, CGA treatment significantly reduced MDA levels in liver samples (167.56±21.17 nmol/mg) and raised SOD (30.85±6.77 U/g). CONCLUSIONS: Chlorogenic acid has a protective effect against salivary gland and liver toxicity induced by SN in rats. This was mediated via the anti-inflammatory and antioxidative properties of CGA and the restoration of oxidant/antioxidant balance in rat salivary gland and liver.

Repeated dose, 28-day oral toxicity study of curcumin, anthocyanins, and sodium nitrite in Wistar rats.

OBJECTIVE: The goal of the present study was to examine the repeated dose 28-day oral toxicity of curcumin, anthocyanins, and sodium nitrite in Wistar rats. METHODS: For this purpose, forty-eight male Wistar rats were randomly divided into 8 groups (n = 6 each), encompassing untreated controls and experimental groups treated with curcumin, anthocyanins, and sodium nitrite. Three rats from each group were sacrificed by cervical dislocation under di-ethyl ether anesthesia after 2 and 4 weeks of therapy, respectively. Blood samples were collected for serum chemistry. All of the animals' livers, hearts, and kidneys were removed and sent for histopathological examination. RESULTS: After two weeks of inquiry, certain groups displayed higher hematological values, while others had lower values compared to the control group. AST, CK, and LDH enzyme activity were higher in groups 2-8, but urea concentrations were higher in groups 6 and 8. After four weeks, the Hb, MCH, and MCHC values in group 4 were greater, as were the WBC levels in groups 4 and 6, whereas other groups had lower MCV and WBC values. The weekly body weight gain was insignificantly different between treatment groups. Throughout the experiment, none of the animals perished. Male rats' liver, kidney, and heart underwent histopathological changes after ingesting curcumin, sodium nitrite, and anthocyanin. CONCLUSION: Based on the findings, rats were more detrimental when curcumin, sodium nitrite, and anthocyanin were ingested together than when they were consumed individually, as evidenced by histopathological abnormalities in the liver, kidneys, and heart.

Clean labelling sodium nitrite at pilot scale: In-situ reduction of nitrate from plant sources and its effects on the overall quality and safety of restructured cooked ham.

Growing health and environmental concerns have increased demand for all-natural products, with a focus on clean labelling. Sodium nitrite is the most widely used additive in the meat industry because it imparts the typical cured flavour and colour to meat products and, most importantly, their microbiological safety. However, due to health concerns, the European Commission is proposing revised regulations to reduce nitrate and nitrite levels in meat products. As a result, the meat industry is actively seeking alternatives. This study explored the production of four cooked hams utilising nitrate-rich vegetable sources combined with two different nitrate-reducing commercial food cultures, alongside a control ham prepared with sodium nitrite (150 ppm). Microbiological, physico-chemical (pH, water activity, nitrate and nitrite concentration, lipid profile, lipid oxidation) and sensory (texture and colour profile) characterisation of the products was carried out. Challenge tests for Listeria monocytogenes, Clostridium sporogenes and Clostridium perfringens have been performed to assess the growth of pathogens, if present in the products. Results revealed comparable microbiological and physico-chemical profiles across ham formulations, with minor differences observed in colour parameters for sample C. The sensory analysis showed that for the pilot ham formulations A and D, there were no significant differences in consumer perception compared to the control ham. In the challenge tests, L. monocytogenes levels were similar in both control and tested hams. There were no significant differences in C. sporogenes and C. perfringens counts at any temperature or between test and control samples. These results indicate that this technology has a potential future in the cured meat sector, as regulators mandate the reduction of added synthetic chemicals and consumers seek healthier and more natural ingredients in their daily diets.

Growth and no-growth boundary of Clostridium perfringens in cooked cured meats - A logistic analysis and development of critical control surfaces using a solid growth medium.

This study was conducted to evaluate the effect of sodium nitrite (NaNO2, 100-200 ppm), sodium erythorbate (SE, 0-547 ppm), sodium tripolyphosphate (STPP, 0-0.5 %), and sodium chloride (NaCl, 2-3 %) on growth of C. perfringens using a solid growth medium and to develop a growth/no-growth boundary (critical control surface, or CCS) to prevent its growth in cooked cured meat under the optimal temperature condition. Melted Shahidi Ferguson Perfringens (SFP) agar, inoculated with a 3-strain spore cocktail and mixed with NaNO2, SE, STPP, and NaCl according to a Box-Behnken response surface experimental design, was dispersed in 96-well microplates and incubated anaerobically in an incubator programmed to remain at 4 °C for 24 h, heat to 80 °C in 1.75 h, quickly (0.5 h) cool to 46 °C (optimum temperature), and then maintain at 46 °C overnight. The plates were examined optically and visually for colony formation. Any well free of growth was designated as no-growth. Logistic regression was used to analyze the growth probability (P) as affected by NaNO2, SE, STPP, and NaCl and define a CSS as meeting the criterion of P < 1/96. The results showed that STPP and the interactions of SE with NaNO2 and NaCl could reduce the growth probability of C. perfringens in SFP agar. The validation of CCS with ground beef showed an accuracy of 96.3 % for no growth of C. perfringens in the inoculated samples. The results of this study proved that cured meat can be formulated with proper combinations of NaNO2, SE, STPP, and NaCl to prevent the growth of C. perfringens even under the optimum temperature condition, thus preventing food poisoning caused by the growth of this microorganism.

Special Report from the CDC: Suicide rates, sodium nitrite-related suicides, and online content, United States.

BACKGROUND: In 2022, suicide ranked as the 11th leading cause of death in the United States with 49,513 deaths. Provisional mortality data from 2022 indicate a 2.8% increase in the number of suicides compared to 2021. This paper examines overall suicide trends, sodium nitrite ingestion as an emerging suicide method, and the role that online forums play in sharing information about suicide methods (including sodium nitrite ingestion). METHODS: Suicides were identified from CDC's National Vital Statistics System (2018-July 2023 provisional) multiple cause-of-death mortality files using International Classification of Diseases (ICD), Tenth Revision underlying cause-of-death codes U03, X60-X84, and Y87.0 and T code T50.6 (antidotes and chelating agents). Google search popularity metrics were captured from January 2019 to January 2023. Case reports of sodium nitrite related suicide and suicide attempts (through February 2024) were identified in the medical and forensic literature. RESULTS: At least 768 suicides involving antidotes and chelating agents (including sodium nitrite) occurred between 2018 and July 2023, set in the context of 268,972 total suicides during that period. Overall, suicides involving antidotes and chelating agents (including sodium nitrite) represent <1% of all suicides, however, numbers are rising. CONCLUSIONS: Suicide methods are known to change over time. These changes can be influenced by, among other factors, online forums and means accessibility, such as internet purchase availability. CDC remains committed to prevention through comprehensive public health strategies that protect individuals, families, and communities. PRACTICAL APPLICATIONS: States and community partners might consider leveraging physicians, emergency responders, and other appropriate crisis response groups to disseminate information on sodium nitrite self-poisoning and its antidote, methylene blue. Efforts should be part of a comprehensive public health approach to suicide prevention.

Co-exposure of microcystin and nitrite enhanced spermatogenic disorders: The role of mtROS-mediated pyroptosis and apoptosis.

Microcystins (MCs) and nitrites are coexisted in the environment and have reproductive toxicity. The combined toxic effect and mechanism of MCs and nitrite on spermatogenesis remain largely unclear. In the present study, co-exposure to microcystin-leucine arginine (MC-LR) and sodium nitrite (NaNO2) aggravated testicular damage of Balb/c mice and mitochondrial impairment of spermatogonia, Sertoli cells, and sperm. Furthermore, MC-LR and NaNO2 reduced sperm density with a synergistic effect. In addition, MC-LR and NaNO2 synergistically induced oxidative stress in the reproductive system by decreasing superoxide dismutase (SOD) activity and glutathione (GSH) levels and increasing levels of mitochondrial reactive oxygen species (mtROS) and reactive oxygen species (ROS). More importantly, mitoquidone mesylate (MitoQ), an inhibitor of mtROS, blocked MC-LR and NaNO2-induced spermatogonia and Sertoli cell apoptosis by inhibiting high expression of Bax, Fadd, Caspase-8, and cleaved-Caspase-3. On the other hand, MitoQ suppressed pyroptosis of Sertoli cells by inhibiting the expression of NLRP3, N-GSDMD, and cleaved-Caspase-1. Additionally, MitoQ alleviated co-exposure-induced sperm density reduction and organ index disorders in F1 generation mice. Together, co-exposure of MC-LR and NaNO2 can enhance spermatogenic disorders by mitochondrial oxidative impairment-mediated germ cell death. This study emphasizes the potential risks of MC-LR and NaNO2 on reproduction in realistic environments and highlights new insights into the cause and treatment of spermatogenic disorders.

The effect and mechanism of combined exposure of MC-LR and NaNO2 on liver lipid metabolism.

Microcystin-LR (MC-LR) and sodium nitrite (NaNO2) co-exist in the environment and are hepatotoxic. The liver has the function of lipid metabolism, but the impacts and mechanisms of MC-LR and NaNO2 on liver lipid metabolism are unclear. Therefore, we established a chronic exposure model of Balb/c mice and used LO2 cells for in vitro verification to investigate the effects and mechanisms of liver lipid metabolism caused by MC-LR and NaNO2. The results showed that after 6 months of exposure to MC-LR and NaNO2, the lipid droplets content was increased, and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were raised in the liver (P < 0.05). Moreover, MC-LR and NaNO2 synergistically induced hepatic oxidative stress by decreasing total superoxide dismutase (T-SOD) activity and glutathione (GSH) levels and increasing malondialdehyde (MDA) content levels. In addition, the levels of Nrf2, HO-1, NQO1 and P-AMPK was decreased and Keap1 was increased in the Nrf2/HO-1 pathway. The key factors of lipid metabolism, SREBP-1c, FASN and ACC, were up-regulated in the liver. More importantly, there was a combined effect on lipid deposition of MC-LR and NaNO2 co-exposure. In vitro experiments, MC-LR and NaNO2-induced lipid deposition and changes in lipid metabolism-related changes were mitigated after activation of the Nrf2/HO-1 signaling pathway by the Nrf2 activator tertiary butylhydroquinone (TBHQ). Additionally, TBHQ alleviated the rise of reactive oxygen species (ROS) in LO2 cells induced by MC-LR and NaNO2. Overall, our findings indicated that MC-LR and NaNO2 can cause abnormal liver lipid metabolism, and the combined effects were observed after MC-LR and NaNO2 co-exposure. The Nrf2/HO-1 signal pathway may be a potential target for prevention and control of liver toxicity caused by MC-LR and NaNO2.

Massive Sodium Nitrite Overdose: A Case for Prehospital Methylene Blue.

Sodium nitrite overdose leads to profound methemoglobinemia and may quickly progress to death. It is an increasingly common method of suicide and is often fatal. Methylene blue is an effective but time-sensitive antidote that has the potential to save lives when administered early. In this case report, we describe a fatal sodium nitrite overdose and the subsequent creation of a prehospital protocol for our large urban Emergency Medical Services system.

Method Validation Study of Dipstick Urinalysis as a Screening Tool for Sodium Nitrite Toxicity.

ABSTRACT: The incidence of suicide by intentional nitrite ingestion has increased since 2017. Limited options exist for commercial laboratory analysis for nitrite/nitrate. This study investigates the use of urine dipsticks for screening at autopsy for potential toxicity with sodium nitrite and, less commonly, alkyl nitrite. Archived samples of blood, urine, vitreous fluid, and gastric contents from 4 sodium nitrite/nitrate cases, 3 alkyl nitrite cases, and 4 control cases were tested using dipsticks. A rapid, strong positive result for nitrite was in the vitreous fluid of all 4-sodium nitrite/nitrate cases, along with 2 positive urine and 1 positive gastric. The 2 alkyl nitrite inhalation toxicity cases had no positive results. One alkyl nitrite ingestion case had a positive urine. The 4 controls had negative urine: equivocal results in 2 vitreous, and 1 positive gastric. Urine dipsticks are a useful adjunct to laboratory testing for nitrite toxicity and provide a rapid, cost-effective tableside result that may guide the need for further testing. Vitreous fluid and urine appear to be the most reliable specimens, although testing of gastric liquid may be useful to corroborate oral ingestion. Dipsticks may not be a reliable adjunct for testing for alkyl nitrite toxicity via inhalation route, likely due to the much lower nitrite concentration compared to nitrite ingestion cases.

Emerging Trends of Self-Harm Using Sodium Nitrite in an Online Suicide Community: Observational Study Using Natural Language Processing Analysis.

Background: There is growing concern around the use of sodium nitrite (SN) as an emerging means of suicide, particularly among younger people. Given the limited information on the topic from traditional public health surveillance sources, we studied posts made to an online suicide discussion forum, "Sanctioned Suicide," which is a primary source of information on the use and procurement of SN. Objective: This study aims to determine the trends in SN purchase and use, as obtained via data mining from subscriber posts on the forum. We also aim to determine the substances and topics commonly co-occurring with SN, as well as the geographical distribution of users and sources of SN. Methods: We collected all publicly available from the site's inception in March 2018 to October 2022. Using data-driven methods, including natural language processing and machine learning, we analyzed the trends in SN mentions over time, including the locations of SN consumers and the sources from which SN is procured. We developed a transformer-based source and location classifier to determine the geographical distribution of the sources of SN. Results: Posts pertaining to SN show a rise in popularity, and there were statistically significant correlations between real-life use of SN and suicidal intent when compared to data from the Centers for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiologic Research (⍴=0.727; P<.001) and the National Poison Data System (⍴=0.866; P=.001). We observed frequent co-mentions of antiemetics, benzodiazepines, and acid regulators with SN. Our proposed machine learning-based source and location classifier can detect potential sources of SN with an accuracy of 72.92% and showed consumption in the United States and elsewhere. Conclusions: Vital information about SN and other emerging mechanisms of suicide can be obtained from online forums.

The bacillithiol pathway is required for biofilm formation in Staphylococcus aureus.

Staphylococcus aureus is a major human pathogen that can cause infections that range from superficial skin and mucosal infections to life threatening disseminated infections. S. aureus can attach to medical devices and host tissues and form biofilms that allow the bacteria to evade the host immune system and provide protection from antimicrobial agents. To counter host-generated oxidative and nitrosative stress mechanisms that are part of the normal host responses to invading pathogens, S. aureus utilizes low molecular weight (LMW) thiols, such as bacillithiol (BSH). Additionally, S. aureus synthesizes its own nitric oxide (NO), which combined with its downstream metabolites may also protect the bacteria against specific host responses. We have previously shown that LMW thiols are required for biofilm formation in Mycobacterium smegmatis and Pseudomonas aeruginosa. Here, we show that the S. aureus bshC mutant strain, which is defective in the last step of the BSH pathway and lacks BSH, is impaired in biofilm formation. We also identify a possible S-nitrosobacillithiol reductase (BSNOR), similar in sequence to an S-nitrosomycothiol reductase found in M. smegmatis and show that the putative S. aureus bsnoR mutant strain has reduced levels of BSH and decreased biofilm formation. Our studies also show that NO plays an important role in biofilm formation and that acidified sodium nitrite severely reduces biofilm thickness. These studies provide insight into the roles of oxidative and nitrosative stress mechanisms on biofilm formation and indicate that BSH and NO are key players in normal biofilm formation in S. aureus.

Ameliorative effect of Odontonema cuspidatum extract against testicular damage induced by sodium nitrite in rats.

Background: Sodium nitrite (NaNO2) is a chemical substance used to enhance taste, add color, and keep food products fit for consumption for a longer time. NaNO2 gives rise to a negative adverse effect on male reproductive function. Odontonema cuspidatum (OC) is a natural plant that possesses antioxidant capacity. Aim: Our research evaluates the potential beneficial effect of OC extract on the harmful effects caused by NaNO2 on the testicular tissue and sperm characteristics of male rats. Methods: Four groups with a total of forty rats: the control, the NaNO2-received group, the OC-administered group, and the fourth group received both NaNO2 and OC. All groups were administered daily for two months. Sperm characteristics, testicular antioxidant status, qRT-PCR, and histopathological changes were evaluated. Results: Coadministration of NaNO2 and OC, in comparison with NaNO2 alone, contributed to a notable enhancement in acrosomal integrity, decreasing sperm abnormalities and restoring serum testosterone levels. Moreover, such coadministration reduced the oxidative stress marker, malondialdehyde (MDA), and increased superoxide dismutase (SOD) in testicular tissue, lowering TNF-α gene expression, and increasing the expression of P450scc and StAR genes. In addition, the NaNO2 and OC combination decreased the testicular histopathological changes and the Caspase-3 and Proliferating cell nuclear antigen (PCNA) immunoexpression in seminiferous tubules compared with the NaNO2 group. Conclusion: The extract of OC exhibited the ability to decrease oxidative stress and ameliorate the detrimental effects caused by NaNO2.

Development and validation of high-performance liquid chromatography-Orbitrap mass spectrometric method for quantification of NDMA in ranitidine drug products and evaluation of antioxidants as inhibitors of classical nitrosation reaction.

RATIONALE: N-Nitroso dimethylamine (NDMA) is a mutagenic impurity detected in several ranitidine products. The amino functional group of ranitidine is a risk factor for classical nitrosation-induced NDMA formation in ranitidine drug products during storage conditions. The United States Food and Drug Administration (US FDA) recommended the use of antioxidants to control NDMA in drug products. Considering the need for sensitive analytics, a liquid chromatography/high-resolution mass spectrometry (LC-HRMS) method was developed and validated to detect NDMA in this pilot study to demonstrate the antioxidants as inhibitors of nitrosation reactions. METHODS: The method, utilizing an EC-C18 column and tuned to atmospheric pressure chemical ionization/selected ion monitoring (APCI/SIM) mode, separated NDMA (m/z: 75.0553; tR: 3.71 min) and ranitidine (m/z: 315.1485; tR: 8.61 min). APCI mode exhibited four times higher sensitivity to NDMA than electrospray ionization (ESI) mode. Classical nitrosation of the dimethyl amino group of ranitidine was studied with sodium nitrite in solid pellets. Antioxidants (alpha-tocopherol, ascorbic acid, and trolox) were evaluated as NDMA attenuators in ranitidine pellets under vulnerable storage conditions. The developed method quantified NDMA levels in samples, extracted with methanol through vortex shaking for 45 min. RESULTS: The method achieved a limit of detection (LOD) and limit of quantitation (LOQ) of 0.01 and 0.05 ng/mL, respectively, with linearity within 1-5000 ng/mL (R1: 0.9995). It demonstrated good intra-day and inter-day precision (% RSD [relative standard deviation]: <2) and accuracy (96.83%-101.72%). Nitrosation of ranitidine induced by nitrite was significant (p < 0.001; R2 = 0.9579) at various sodium nitrite levels. All antioxidants efficiently attenuated NDMA formation during ranitidine nitrosation. Ascorbic acid exhibited the highest NDMA attenuation (96.98%), followed by trolox (90.58%). This study recommends 1% ascorbic acid and trolox as potent NDMA attenuators in ranitidine drug products. CONCLUSIONS: This study compared the effectiveness of antioxidants as NDMA attenuators in ranitidine under storage conditions susceptible to NDMA generation. The study concluded that ascorbic acid and trolox are potent inhibitors of NDMA formation and nitrosation attenuators in ranitidine drug products.

Nitric oxide-releasing thiolated starch nanoparticles embedded in gelatin sponges for wound dressing applications.

This study introduces a novel wound dressing by combining nitric oxide-releasing thiolated starch nanoparticles (NO-TS NPs) with gelatin. First, starch was thiolated (TS), and then its nanoparticles were prepared (TS NPs). Subsequently, NPs were covalently bonded to sodium nitrite to obtain NO-releasing TS NPs (NO-TS-NPs) that were incorporated into gelatin sponges at various concentrations. The resulting spherical TS NPs had a mean size of 85.42 ± 5.23 nm, which rose to 100.73 ± 7.41 nm after bonding with sodium nitrite. FTIR spectroscopy confirmed S-nitrosation on the NO-TS NPs' surface, and morphology analysis showed well-interconnected pores in all sponges. With higher NO-TS NPs content, pore size, porosity, and water uptake increased, while compressive modulus and strength decreased. Composites exhibited antibacterial activity, particularly against E. coli, with enhanced efficacy at higher NPs' concentrations. In vitro release studies demonstrated Fickian diffusion, with faster NO release in sponges containing more NPs. The released NO amounts were non-toxic to fibroblasts, but samples with fewer NO-TS NPs exhibited superior cellular density, cell attachment, and collagen secretion. Considering the results, including favorable mechanical strength, release behavior, antibacterial and cellular properties, gelatin sponges loaded with 2 mg/mL of NO-TS NPs can be suitable for wound dressing applications.

Seasonal efficacy and risks from a sodium nitrite toxic bait for wild pigs.

BACKGROUND: Wild pigs (Sus scrofa) are an invasive and destructive species throughout many regions of the world. A sodium nitrite (SN) toxic bait is currently used in Australia and being developed for use in the US and other countries to combat the increasing populations of wild pigs. In the US, efforts to modify the Australian SN-toxic bait and baiting strategy have focused on reducing issues with non-target animals accessing the SN-toxic bait spilled outside of bait stations by wild pigs. We tested and compared modifications for efficacy (with wild pigs) and hazards (with non-targets) in north-central Texas, US during summer (July 2021) and winter (March 2023) seasons. RESULTS: During both seasons we found that visitation to the bait sites declined 94-99% after deploying the SN-toxic bait, and we found a total of 106 dead wild pigs, indicating considerable lethality for the local population. Prior to deploying the SN-toxic bait, Global Positioning System (GPS)-collared wild pigs were more likely to cease visiting bait sites during summer when foraging resources were abundant. Farrowing decreased visitation to bait sites during the winter. We observed no dead non-targets during summer; winter results showed an average of 5.2 dead migrating birds per bait site (primarily Dark-eye juncos [Junco hyemalis]) from consuming SN-toxic bait spilled by wild pigs. The presence and winter-foraging behaviors of migrating birds appeared to increase hazards for those species. CONCLUSION: The current formulation of SN-toxic bait was effective at removing wild pigs during both seasons, however it is clear that different baiting strategies may be required in winter when migrating birds are present. Baiting wild pigs prior to farrowing during the winter, and during drier summers, may further improve efficacy of the bait. Reducing hazards to non-targets could be achieved by refining the SN-toxic bait or modifying bait stations to decrease the potential for spillage, decreasing environmental persistence if spilled, or decreasing attractiveness to migrating birds. © 2024 Society of Chemical Industry. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.