Analysis of Fomepizole Elimination in Methanol- and Ethylene Glycol-Poisoned Patients.

Introduction: Fomepizole is an anti-metabolite therapy that is used to diminish the toxicity from methanol or ethylene glycol. Although its elimination kinetics have been well described in healthy human subjects, the elimination in poisoned patients have only been described in a few isolated cases. This study was designed to relate the elimination of fomepizole in a series of poisoned patients to that in healthy humans.

Fomepizole dosing during continuous renal replacement therapy - an observational study.

Background: Fomepizole is the preferred antidote for treatment of methanol and ethylene glycol poisoning, acting by inhibiting the formation of the toxic metabolites. Although very effective, the price is high and the availability is limited. Its availability is further challenged in situations with mass poisonings.

Diethylene glycol produces nephrotoxic and neurotoxic effects in female rats.

Context: Diethylene glycol (DEG) is an organic compound found in household products but also as a counterfeit solvent in medicines. DEG poisonings are characterized by acute kidney injury (AKI) and by neurological sequelae such as decreased reflexes or face and limb weakness. Previous studies in male rats have demonstrated that neurotoxic effects develop only with the establishment of AKI, but the dose sensitivity of females to DEG toxicity is unknown.

Neurotoxic effects of nephrotoxic compound diethylene glycol.

Context: Diethylene glycol (DEG) is an organic compound found in household products but also as an adulterant in medicines by acting as a counterfeit solvent. DEG poisonings have been characterized predominately by acute kidney injury (AKI), but also by delayed neurological sequelae such as decreased reflexes or face and limb weakness.

Objectives: Characterizing the neurological symptoms of DEG poisoning in a subacute animal model would create a clearer picture of overall toxicity and possibly make mechanistic connections between kidney injury and neuropathy.

Calcium Oxalate Monohydrate is Associated with Endothelial Cell Toxicity But Not with Reactive Oxygen Species Accumulation.

One characteristic of ethylene glycol overdose is a cardiopulmonary syndrome including hypertension and pulmonary edema with pathology indicating damage to the endothelium of heart, lung and brain vessels. The mechanism of the cardiopulmonary toxicity is unknown, but has been linked with accumulation of the metabolite calcium oxalate monohydrate (COM) in the endothelium. These studies have evaluated the hypothesis that COM or the oxalate ion produces endothelial damage in vitro and that damage is linked with induction of reactive oxygen species (ROS).

Consensus statements on the approach to patients in a methanol poisoning outbreak.

Methanol poisoning is an important cause of mortality and morbidity worldwide. Although it often occurs as smaller sporadic events, epidemic outbreaks are not uncommon due to the illicit manufacture and sale of alcoholic beverages. We aimed to define methanol poisoning outbreak (MPO), outline an approach to triaging an MPO, and define criteria for prioritizing antidotes, extracorporeal elimination treatments (i.

Curcumin gum formulation for prevention of oral cavity head and neck squamous cell carcinoma.

Objectives/hypothesis: Head and neck squamous cell carcinoma represents the sixth most common cancer. As a result of field cancerization, second primaries and recurrences are high. Hence, research has focused on chemoprevention.

Human health assessment for long-term oral ingestion of diethylene glycol.

Diethylene glycol (DEG) is an organic chemical that is used mostly as a chemical intermediate and has minor uses as a solvent or antifreeze in consumer products; these minor uses could result in potential human exposure. Potential short and long-term human exposures also occur from misuses. The considerable reporting of DEG misuses as a substitute for other solvents in drug manufacturing and summaries of important events in the history of DEG poisonings are reviewed.

In-vivo evidence of nephrotoxicity and altered hepatic function in rats following administration of diglycolic acid, a metabolite of diethylene glycol.

Context: Diglycolic acid (DGA) is one of the two primary metabolites of diethylene glycol (DEG). DEG is an industrial solvent that has been implicated in mass poisonings resulting from product misuse in the United States and worldwide, with the hallmark toxicity being acute kidney injury, hepatotoxicity, encephalopathy and peripheral neuropathy. Our laboratory has generated in-vitro evidence suggesting that DGA is the metabolite responsible for the proximal tubule necrosis and decreased kidney function observed following DEG ingestion.

Diglycolic acid, the toxic metabolite of diethylene glycol, chelates calcium and produces renal mitochondrial dysfunction in vitro.

Context: Diethylene glycol (DEG) has caused many cases of acute kidney injury and deaths worldwide. Diglycolic acid (DGA) is the metabolite responsible for the renal toxicity, but its toxic mechanism remains unclear.

Objective: To characterize the mitochondrial dysfunction produced from DGA by examining several mitochondrial processes potentially contributing to renal cell toxicity.

Antidotes for poisoning by alcohols that form toxic metabolites.

The alcohols, methanol, ethylene glycol and diethylene glycol, have many features in common, the most important of which is the fact that the compounds themselves are relatively non-toxic but are metabolized, initially by alcohol dehydrogenase, to various toxic intermediates. These compounds are readily available worldwide in commercial products as well as in homemade alcoholic beverages, both of which lead to most of the poisoning cases, from either unintentional or intentional ingestion. Although relatively infrequent in overall occurrence, poisonings by metabolically-toxic alcohols do unfortunately occur in outbreaks and can result in severe morbidity and mortality.

Diethylene glycol-induced toxicities show marked threshold dose response in rats.

Diethylene glycol (DEG) exposure poses risks to human health because of widespread industrial use and accidental exposures from contaminated products. To enhance the understanding of the mechanistic role of metabolites in DEG toxicity, this study used a dose response paradigm to determine a rat model that would best mimic DEG exposure in humans. Wistar and Fischer-344 (F-344) rats were treated by oral gavage with 0, 2, 5, or 10g/kg DEG and blood, kidney and liver tissues were collected at 48h.

Quantitation of diethylene glycol and its metabolites by gas chromatography mass spectrometry or ion chromatography mass spectrometry in rat and human biological samples.

The misuse of the commonly used chemical diethylene glycol (DEG) has lead to many poisonings worldwide. Methods were developed for analysis of DEG and its potential metabolites; ethylene glycol, glycolic acid, oxalic acid, diglycolic acid and hydroxyethoxy acetic acid in human urine, serum and cerebrospinal fluid samples, collected following a DEG-associated poisoning in the Republic of Panama during 2006. In addition, methods were developed for rat blood, urine, kidney and liver tissue to support toxicokinetic analysis during the conduct of DEG acute toxicity studies in the rat.

Characterizing concentrations of diethylene glycol and suspected metabolites in human serum, urine, and cerebrospinal fluid samples from the Panama DEG mass poisoning.

Context: Diethylene glycol (DEG) mass poisoning is a persistent public health problem. Unfortunately, there are no human biological data on DEG and its suspected metabolites in poisoning. If present and associated with poisoning, the evidence for use of traditional therapies such as fomepizole and/or hemodialysis would be much stronger.

Hysteroscopic tubal sterilization: an evidence-based analysis.

Background: Hysteroscopic tubal sterilization is a minimally invasive alternative to laparoscopic tubal ligation for women who want permanent contraception. The procedures involves non-surgical placement of permanent microinserts into both fallopian tubes. Patients must use alternative contraception for at least 3 months postprocedure until tubal occlusion is confirmed.

Discharge planning in chronic conditions: an evidence-based analysis.

Background: Chronically ill people experience frequent changes in health status accompanied by multiple transitions between care settings and care providers. Discharge planning provides support services, follow-up activities, and other interventions that span pre-hospital discharge to post-hospital settings.

Objective: To determine if discharge planning is effective at reducing health resource utilization and improving patient outcomes compared with standard care alone.

Diglycolic acid inhibits succinate dehydrogenase activity in human proximal tubule cells leading to mitochondrial dysfunction and cell death.

Diethylene glycol (DEG) is a solvent used in consumer products allowing the increased risk for consumer exposure. DEG metabolism produces two primary metabolites, 2-hydroxyethoxyacetic acid (2-HEAA) and diglycolic acid (DGA). DGA has been shown to be the toxic metabolite responsible for the proximal tubule cell necrosis seen in DEG poisoning.

Aluminum citrate blocks toxicity of calcium oxalate crystals by preventing binding with cell membrane phospholipids.

Background/aims: Renal damage from ethylene glycol and primary hyperoxaluria is linked to accumulation of calcium oxalate monohydrate (COM) crystals in the renal proximal tubule (PT). In vitro studies have shown that aluminum citrate (AC), uniquely among citrate salts, blocks COM cytotoxicity to tubular cells. These studies were designed to evaluate the interaction of COM with membrane phospholipids and the ability of AC to reduce COM toxicity by interfering with this interaction.

Oral Reference Dose for ethylene glycol based on oxalate crystal-induced renal tubule degeneration as the critical effect.

Several risk assessments have been conducted for ethylene glycol (EG). These assessments identified the kidney as the primary target organ for chronic effects. None of these assessments have incorporated the robust database of species-specific toxicokinetic and toxicodynamic studies with EG and its metabolites in defining uncertainty factors used in reference value derivation.