This review paper highlights the research on thrives for nitrate reduction by transition metal chalcogenides (TMCs) to produce ammonia. The exposure of humans to nitrate in the environment via public drinking water supplies is on the increase due to the elevated usage of inorganic fertilizers and animal manure in agricultural lands in various regions of the world. Many regions of the world has already set a permissible limit for nitrate in drinking water so as to prevent methemoglobinemia in children, birth defects, thyroid dysfunction and disease, various cancers, and cyanosis that culminates into asphyxia. Also, serious health disorders may occur due to ingestion of excess nitrate, such as cardiovascular disorder, genetic mutation, and diabetes. Recently, TMCs have attracted the keen interest of the scientists/researchers due to their unique tunable properties such as heterojunction formation with noble metals, morphological engineering through various synthesis techniques, elemental doping, and tunable edge active site and surface defects that induce active sites transformation at the basal planes. Irrespective of these unique surface properties, TMCs have the shortcomings of increasing surface hydrogen binding energy and Gibbs free energy change, which enhances charge-carrier separation and hydrogen evolution reaction (HER). Future research outlook should focus on the surface engineering of TMCs in terms of minimizing the formation of heterojunction, which will limit proton/electron-transfer kinetics, shifting the chemical equilibrium of HER through catalyst engineering that will mitigate the adsorption of hydrogen species, regulating the crystal phase, blocking the HER active sites, and introducing strain effects that will suppress HER and boost nitrogen reduction reaction (NRR). These strategies will suppress HER and increase the efficiency of NRR.

Acquired methemoglobinemia is an uncommon but potentially life-threatening disorder characterized by oxidation of hemoglobin iron into the ferric state, resulting in impaired oxygen delivery and functional anemia. Patients may present with cyanosis, persistent hypoxemia, and discordance between pulse oximetry and arterial oxygen saturation (SaO2). Although medications and industrial chemicals are well-recognized causes, herbal and traditional remedies remain underreported aetiologies. A 35-year-old man presented with a sudden-onset generalized tonic-clonic seizure followed by persistent hypoxemia and peripheral cyanosis after ingestion of a home-prepared herbal (Ayurvedic) decoction. The blood sample demonstrated characteristic chocolate-brown discoloration. Oxygen saturation remained approximately 85% despite supplemental oxygen therapy. Arterial blood gas (ABG) analysis demonstrated preserved arterial oxygen tension (PaO2 167 mmHg) with a calculated SaO2 of 97.3%, indicating a characteristic saturation gap. Co-oximetry demonstrated a methemoglobin level of 19%. The diagnosis of methemoglobinemia was supported by refractory hypoxemia, cyanosis, chocolate-brown blood discoloration, saturation gap, and co-oximetry-confirmed methemoglobinemia (19%). The patient improved rapidly following treatment with intravenous methylene blue, anticonvulsants, and supportive care. There was a rapid disappearance of cyanosis; oxygen saturation returned to normal with full neurological recovery. This example highlights the importance of checking for methemoglobinemia in patients with symptoms of unexplained cyanosis, refractory hypoxemia, and a mismatch between pulse oximetry and arterial oxygen levels, particularly following exposure to herbal or traditional preparations. Recognition of these findings facilitated prompt diagnosis and treatment in our patient.

Rasburicase (brand name Elitek) is a uric oxidase used to treat the high levels of uric acid that are associated with tumor lysis syndrome (TLS). Tumor lysis syndrome is a potentially life-threatening condition caused by rapid break down of tumor cells during chemotherapy. Tumor lysis syndrome is associated with the treatment of aggressive lymphoma and leukemia, but it may also occur with other tumors including solid tumors. Massive cell breakdown results in the release of potassium, phosphate, and uric acid into the circulation. Urate crystals can precipitate in the kidneys, causing acute kidney damage. Prophylaxis and treatment of TLS involve aggressive intravenous (IV) hydration and the use of drugs to lower uric acid levels. Rasburicase breaks down uric acid to a more soluble metabolite (allantoin), which is then eliminated by the kidneys. A by-product of this reaction is hydrogen peroxide, an oxidizing agent. Red blood cells that lack the enzyme glucose-6-phosphate dehydrogenase (G6PD) are sensitive to oxidative damage caused by agents like hydrogen peroxide due to a deficiency in nicotinamide adenine dinucleotide phosphate (NADPH). Once exposed, the red blood cells become rigid, trapped, and are rapidly broken down (hemolysis). This can lead to a deficiency of mature red blood cells (hemolytic anemia) and the production of red blood cells with abnormally high levels of methemoglobin (methemoglobinemia). Approximately 400 million people worldwide have G6PD deficiency. Most of these individuals are asymptomatic. However, they are at risk of life-threating hemolytic reactions and methemoglobinemia if given oxidizing drugs such as rasburicase. Rasburicase is contraindicated in individuals with G6PD deficiency. The FDA-approved drug label states that individuals at higher risk for G6PD deficiency should be screened before starting rasburicase therapy, for example, individuals of African or Mediterranean ancestry (Table 1) (1). Approximately 12% of African-Americans have G6PD deficiency. A rare cause of methemoglobinemia is a deficiency of antioxidant enzymes such as cytochrome b5 reductase 3 (CYB5R3). The drug label states it is not known whether individuals who have a deficiency of this enzyme, or another enzyme with antioxidant activity, are at increased risk of methemoglobinemia or hemolytic anemia during rasburicase therapy. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has published dosing recommendations for rasburicase based on G6PD phenotype (Table 2). The CPIC states for individuals with normal G6PD phenotype, there is no reason to withhold rasburicase based on G6PD status. For individuals who are G6PD deficient, with or without hemolytic anemia, rasburicase is contraindicated. For individuals who have a variable G6PD phenotype, G6PD enzyme activity must be measured to ascertain that G6PD status is normal. For cases where rasburicase is contraindicated, alternative drugs include allopurinol (2).

Pegloticase (brand name Krystexxa) is used to treat the high levels of uric acid associated with refractory gout. The use of pegloticase is reserved for individuals with symptomatic, chronic gout who have not responded to, or are unable to take, conventional gout treatments. Pegloticase is given once every 2 weeks as an intravenous infusion, and is given in a healthcare setting that is prepared to manage infusion reactions and anaphylaxis (1). Pegloticase is a pegylated urate oxidase – a modified version of the enzyme that catalyzes the oxidation of uric acid to 5-hydroxyisourate and hydrogen peroxide in most mammalian species. However, urate oxidase is not active in humans due to an inactivating mutation in the gene (2). Subsequent hydrolysis and decarboxylation of 5-hydroxyisourate leads to the formation of a more soluble metabolite (allantoin), which is then excreted by the kidneys. Red blood cells that lack the glucose-6-phosphate dehydrogenase (G6PD) enzyme are sensitive to oxidative damage caused by agents like hydrogen peroxide. Once exposed, the red blood cells become rigid, trapped, and are rapidly broken down (hemolysis). This can lead to a deficiency of mature red blood cells (hemolytic anemia) and the production of red blood cells with abnormally high levels of methemoglobin (methemoglobinemia). Approximately 400 million people worldwide have G6PD deficiency. Most of these individuals are asymptomatic. However, they are at risk of life-threating hemolytic reactions and methemoglobinemia if given oxidizing drugs such as pegloticase. Pegloticase is contraindicated in individuals with G6PD deficiency. The FDA-approved label states that individuals at higher risk for G6PD deficiency should be screened before starting pegloticase therapy, with specific examples including individuals of African, Mediterranean (including Southern European and Middle Eastern), and South Asian ancestry (Table 1) (1). Importantly, approximately 12% of African-Americans have G6PD deficiency.

Poppers (alkyl nitrites) produce a headrush and relax smooth muscle when inhaled. As such, poppers are often used to facilitate comfortable and pleasurable sex among gay, bisexual, and queer men as well as trans and non-binary people. While policy measures to control access to poppers vary across international jurisdictions (ranging from criminalization to prescription or grey market access), limited evidence is available to inform effective health and regulatory policy. Differential classification (i.e., enacting varied regulatory measures, controlling poppers formulations differently according to their risk profiles) has recently been established in Australia as a means to reduce harms. Despite a lack of consensus among regulators with respect to differential classification as a public health strategy for poppers use, the possibilities to reduce harm may be far greater than currently recognized. Through this essay, we examine the evidence behind differential classification of alkyl nitrites, with an eye to improving policy and informing research across jurisdictions. Drawing on research from the 1890s to present day, we argue that current discourse has not appropriately captured data available to elucidate and disentangle health outcomes across different alkyl nitrite formulations; yet, underutilized data suggest important reductions to risk that may be possible through differential classification. Promising findings from archival research include diminished propensity for overdose (via methemoglobinemia) observed in octyl and tert-butyl nitrite, which may provide an avenue to reduce poppers-related deaths, and variation in physiological outcomes across the alkyl nitrites which may help to explain anecdotal reports of variation in health outcomes such as headache.