Hydrogen Sulfide Toxicity: Mechanism of Action, Clinical Presentation, and Countermeasure Development.

INTRODUCTION: Hydrogen sulfide (H2S) is found in various settings. Reports of chemical suicide, where individuals have combined readily available household chemicals to produce lethal concentrations of H2S, have demonstrated that H2S is easily produced. Governmental agencies have warned of potential threats of use of H2S for a chemical attack, but currently there are no FDA-approved antidotes for H2S. An ideal antidote would be one that is effective in small volume, readily available, safe, and chemically stable. In this paper we performed a review of the available literature on the mechanism of toxicity, clinical presentation, and development of countermeasures for H2S toxicity. DISCUSSION: In vivo, H2S undergoes an incomplete oxidation after an exposure. The remaining non-oxidized H2S is found in dissolved and combined forms. Dissolved forms such as H2S gas and sulfhydryl anion can diffuse between blood and tissue. The combined non-soluble forms are found as acid-labile sulfides and sulfhydrated proteins, which play a role in toxicity. Recent countermeasure development takes into account the toxicokinetics of H2S. Some countermeasures focus on binding free hydrogen sulfide (hydroxocobalamin, cobinamide); some have direct effects on the mitochondria (methylene blue), while others work by mitigating end organ damage by generating other substances such as nitric oxide (NaNO2). CONCLUSION: H2S exists in two main pools in vivo after exposure. While several countermeasures are being studied for H2S intoxication, a need exists for a small-volume, safe, highly effective antidote with a long shelf life to treat acute toxicity as well as prevent long-term effects of exposure.

Trimetazidine in conditions other than coronary disease, old drug, new tricks?

Trimetazidine (TMZ) has traditionally been used as an anti-ischemic drug for coronary artery disease by selectively inhibiting the mitochondrial long-chain 3-ketoacyl-CoA thiolase. Recently, new applications for this therapy have been investigated. This article reviews alternative uses for TMZ in non-coronary artery diseases, such as non-ischemic cardiomyopathy, sepsis, myocardial dysfunction induced by anti-cancer drugs, diabetic cardiomyopathy and contrast-induced nephropathy.

Vitamin C pretreatment protects from nickel-induced acute nephrotoxicity in mice.

Nickel is an abundant carcinogenic and nephrotoxic metal whose activity leads to renal impairment. Previous studies have shown a protective effect of simultaneous vitamin C administration on acute and chronic nickel toxicity. However, very little research relating to the effect of vitamin C pretreatment in preventing nickel-induced acute nephrotoxicity is available. Therefore, the present study aimed to determine the efficiency of vitamin C (VC) pretreatment in preventing acute renal toxicity of nickel. Mice were pretreated orally with vitamin C (16.6 mg kg-1 body weight, b.w.) for seven consecutive days, prior to intraperitoneal (i.p.) administration of nickel chloride at different doses (3, 5, and 10 mg Ni kg-1 b.w.) for an exposure period of 24 hours. Thereafter, animals were killed and kidney tissue and blood samples were taken for histological examination and biochemical marker analyses. Vitamin C pretreatment alone did not alter the levels of serum kidney markers (creatinine, urea, and uric acid). However, treatment with Ni alone showed a significant increase in the levels of serum creatinine, urea, and uric acid with marked necrotic epithelial cells and infiltration by inflammatory cells in kidney sections as compared to the control group. Pretreatment with vitamin C and treatment with Ni at all doses tested for 24 hours showed a significant decrease in the levels of serum creatinine, urea, and uric acid, as well as an improvement in histological changes compared to those previously seen in the group treated with Ni alone. It is concluded that vitamin C pretreatment effectively improved renal function and tissue damage caused by nickel.

Severe cefepime-induced status epilepticus treated with haemofiltration / Estatus epiléptico grave inducido por cefepime tratado con hemofiltración

Neurotoxicity caused by cefepime may occur predominantly in patients with impaired renal function. A case of a cefepime-induced non-convulsive status epilepticus (NCSE) is presented. A 65-year-old woman suffered a severe NCSE due to cefepime in the presence of acute renal failure, requiring coma induction with sodium thiopental. A serious interaction between valproic acid (VPA) and meropenem was also produced after changing cefepime to meropenem. Continuous veno-venous haemofiltration was employed to improve cefepime clearance, and the patient progressively regained her previous mental condition. In conclusion, the cefepime dose must be adjusted according to renal function in order to avoid toxicity in patients with renal failure. Electroencephalogram should be considered in cases of acute confusional state in patients receiving cefepime, to achieve early detection of NCSE. Continuous renal replacement therapy may be successfully employed in severe cases in order to accelerate cefepime removal. Likewise, meropenem should not be used concomitantly with VPA (AU)

La neurotoxicidad por cefepime puede producirse principalmente en pacientes con insuficiencia renal. Presentamos un caso de status epiléptico no convulsivo producido por cefepime. Una mujer de 65 años con fracaso renal agudo en tratamiento con cefepime sufrió un episodio grave de status epiléptico no convulsivo que requirió inducción de coma barbitúrico con tiopental sódico. Tras el cambio de cefepime a meropenem se produjo también una interacción grave entre meropenem y ácido valproico. Se utilizó hemofiltración venovenosa continua para acelerar el aclaramiento de cefepime y la paciente recuperó progresivamente su situación neurológica previa. En conclusión, la dosis de cefepime debe ser ajustada a la función renal para evitar toxicidad en pacientes con insuficiencia renal. Debería considerarse la utilización del electroencefalograma en casos de estado confusional agudo en pacientes en tratamiento con cefepime para un diagnóstico precoz del status epiléptico no convulsivo. La terapia continua de reemplazo renal puede ser empleada en casos graves para acelerar la eliminación de cefepime. Además el meropenem no debe de utilizarse concomitantemente con el ácido valproico (AU)