A retrospective analysis of glycol and toxic alcohol ingestion: utility of anion and osmolal gaps

<p>Abstract</p> <p>Background</p> <p>Patients ingesting ethylene glycol, isopropanol, methanol, and propylene glycol ('toxic alcohols') often present with non-specific signs and symptoms. Definitive diagnosis of toxic alcohols has traditionally been by gas chromatography (GC), a technique not commonly performed on-site in hospital clinical laboratories. The objectives of this retrospective study were: 1) to assess the diagnostic accuracy of the osmolal gap in screening for toxic alcohol ingestion and 2) to determine the common reasons other than toxic alcohol ingestion for elevated osmolal gaps.</p> <p>Methods</p> <p>Electronic medical records from an academic tertiary care medical center were searched to identify all patients in the time period from January 1, 1996 to September 1, 2010 who had serum/plasma ethanol, glucose, sodium, blood urea nitrogen, and osmolality measured simultaneously, and also all patients who had GC analysis for toxic alcohols. Detailed chart review was performed on all patients with osmolal gap of 9 or greater.</p> <p>Results</p> <p>In the study period, 20,669 patients had determination of serum/plasma ethanol and osmolal gap upon presentation to the hospitals. There were 341 patients with an osmolal gap greater than 14 (including correction for estimated contribution of ethanol) on initial presentation to the medical center. Seventy-seven patients tested positive by GC for one or more toxic alcohols; all had elevated anion gap or osmolal gap or both. Other than toxic alcohols, the most common causes for an elevated osmolal gap were recent heavy ethanol consumption with suspected alcoholic ketoacidosis, renal failure, shock, and recent administration of mannitol. Only 9 patients with osmolal gap greater than 50 and no patients with osmolal gap greater than 100 were found to be negative for toxic alcohols.</p> <p>Conclusions</p> <p>Our study concurs with other investigations that show that osmolal gap can be a useful diagnostic test in conjunction with clinical history and physical examination.</p

Time course study of oxidative and nitrosative stress and antioxidant enzymes in K(2)Cr(2)O(7)-induced nephrotoxicity

BACKGROUND: Potassium dichromate (K(2)Cr(2)O(7))-induced nephrotoxicity is associated with oxidative and nitrosative stress. In this study we investigated the relation between the time course of the oxidative and nitrosative stress with kidney damage and alterations in the following antioxidant enzymes: Cu, Zn superoxide dismutase (Cu, Zn-SOD), Mn-SOD, glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT). METHODS: Nephrotoxicity was induced in rats by a single injection of K(2)Cr(2)O(7). Groups of animals were sacrificed on days 1,2,3,4,6,8,10, and 12. Nephrotoxicity was evaluated by histological studies and by measuring creatinine clearance, serum creatinine, blood urea nitrogen (BUN), and urinary excretion of N-acetyl-β-D-glucosaminidase (NAG) and total protein. Oxidative and nitrosative stress were measured by immunohistochemical localization of protein carbonyls and 3-nitrotyrosine, respectively. Cu, Zn-SOD, Mn-SOD, and CAT were studied by immunohistochemical localization. The activity of total SOD, CAT, GPx, and GR was also measured as well as serum and kidney content of chromium and urinary excretion of NO(2 )(-)/NO(3)(-). Data were compared by two-way analysis of variance followed by a post hoc test. RESULTS: Serum and kidney chromium content increased reaching the highest value on day 1. Nephrotoxicity was made evident by the decrease in creatinine clearance (days 1–4) and by the increase in serum creatinine (days 1–4), BUN (days 1–6), urinary excretion of NAG (days 1–4), and total protein (day 1–6) and by the structural damage to the proximal tubules (days 1–6). Oxidative and nitrosative stress were clearly evident on days 1–8. Urinary excretion of NO(2)(-)/NO(3)(- )decreased on days 2–6. Mn-SOD and Cu, Zn-SOD, estimated by immunohistochemistry, and total SOD activity remained unchanged. Activity of GPx decreased on days 3–12 and those of GR and CAT on days 2–10. Similar findings were observed by immunohistochemistry of CAT. CONCLUSION: These data show the association between oxidative and nitrosative stress with functional and structural renal damage induced by K(2)Cr(2)O(7). Renal antioxidant enzymes were regulated differentially and were not closely associated with oxidative or nitrosative stress or with kidney damage. In addition, the decrease in the urinary excretion of NO(2)(-)/NO(3)(- )was associated with the renal nitrosative stress suggesting that nitric oxide was derived to the formation of reactive nitrogen species involved in protein nitration

Hydration of dicalcium silicate and diffusion through neo-formed calcium-silicate-hydrates at weathered surfaces control the long-term leaching behaviour of basic oxygen furnace (BOF) steelmaking slag

Alkalinity generation and toxic trace metal (such as vanadium) leaching from basic oxygen furnace (BOF) steel slag particles must be properly understood and managed by pre-conditioning if beneficial reuse of slag is to be maximised. Water leaching under aerated conditions was investigated using fresh BOF slag at three different particle sizes (0.5–1.0, 2–5 and 10 × 10 × 20 mm blocks) and a 6-month pre-weathered block. There were several distinct leaching stages observed over time associated with different phases controlling the solution chemistry: (1) free-lime (CaO) dissolution (days 0–2); (2) dicalcium silicate (Ca₂SiO₄) dissolution (days 2–14) and (3) Ca–Si–H and CaCO₃ formation and subsequent dissolution (days 14–73). Experiments with the smallest size fraction resulted in the highest Ca, Si and V concentrations, highlighting the role of surface area in controlling initial leaching. After ~2 weeks, the solution Ca/Si ratio (0.7–0.9) evolved to equal those found within a Ca–Si–H phase that replaced dicalcium silicate and free-lime phases in a 30- to 150-μm altered surface region. V release was a two-stage process; initially, V was released by dicalcium silicate dissolution, but V also isomorphically substituted for Si into the neo-formed Ca–Si–H in the alteration zone. Therefore, on longer timescales, the release of V to solution was primarily controlled by considerably slower Ca–Si–H dissolution rates, which decreased the rate of V release by an order of magnitude. Overall, the results indicate that the BOF slag leaching mechanism evolves from a situation initially dominated by rapid hydration and dissolution of primary dicalcium silicate/free-lime phases, to a slow diffusion limited process controlled by the solubility of secondary Ca–Si–H and CaCO₃ phases that replace and cover more reactive primary slag phases at particle surfaces

Punica granatum L. protects mice against hexavalent chromium-induced genotoxicity

This study investigated the chemoprotective effects of Punica granatum L. (Punicaceae) fruits alcoholic extract (PGE) on mice exposed to hexavalent chromium [Cr(VI)]. Animals were pretreated with PGE (25, 50 or 75 mg/kg/day) for 10 days and subsequently exposed to a sub-lethal dose of Cr(VI) (30 mg/kg). The frequency of micronucleated polychromatic erythrocytes in the bone marrow was investigated and the Cr(VI) levels were measured in the kidneys, liver and plasm. For the survival analysis, mice were previously treated with PGE for 10 days and exposed to a single lethal dose of Cr(VI) (50 mg/kg). Exposure to a sub-lethal dose of Cr(VI) induced a significant increase in the frequency of micronucleated cells. However, the prophylactic treatment with PGE led to a reduction of 44.5% (25 mg/kg), 86.3% (50 mg/kg) and 64.2% (75 mg/kg) in the incidence of micronuclei. In addition, the 50 mg/kg dose of PGE produced a higher chemoprotective effect, since the survival rate was 90%, when compared to that of the non-treated group. In these animals, reduced amounts of chromium were detected in the biological materials, in comparison with the other groups. Taken together, the results demonstrated that PGE exerts a protective effect against Cr(VI)-induced genotoxicity

Whole organisms or pure compounds? entourage effect versus drug specificity

As the therapeutic use of sacred plants and fungi becomes increasingly accepted by Western medicine, a tug of war has been taking place between those who advocate the traditional consumption of whole organisms and those who defend exclusively the utilization of purified compounds. The attempt to reduce organisms to single active principles is challenged by the sheer complexity of traditional medicine. Ayahuasca, for example, is a concoction of at least two plant species containing multiple psychoactive substances with complex interactions. Similarly, cannabis contains dozens of psychoactive substances whose specific combinations in different strains correspond to different types of therapeutic and cognitive effects. The “entourage effect” refers to the synergistic effects of the multiple compounds present in whole organisms, which may potentiate clinical efficacy while attenuating side effects. In opposition to this view, mainstream pharmacology is adamant about the need to use purified substances, presumably more specific and safe. In this chapter, I will review the evidence on both sides to discuss the scientific, economic, and political implications of this controversy. The evidence indicates that it is time to embrace the therapeutic complexity of psychedelics.2019-07-3

Gastrointestinal decontamination in the acutely poisoned patient

ObjectiveTo define the role of gastrointestinal (GI) decontamination of the poisoned patient.Data sourcesA computer-based PubMed/MEDLINE search of the literature on GI decontamination in the poisoned patient with cross referencing of sources.Study selection and data extractionClinical, animal and in vitro studies were reviewed for clinical relevance to GI decontamination of the poisoned patient.Data synthesisThe literature suggests that previously, widely used, aggressive approaches including the use of ipecac syrup, gastric lavage, and cathartics are now rarely recommended. Whole bowel irrigation is still often recommended for slow-release drugs, metals, and patients who "pack" or "stuff" foreign bodies filled with drugs of abuse, but with little quality data to support it. Activated charcoal (AC), single or multiple doses, was also a previous mainstay of GI decontamination, but the utility of AC is now recognized to be limited and more time dependent than previously practiced. These recommendations have resulted in several treatment guidelines that are mostly based on retrospective analysis, animal studies or small case series, and rarely based on randomized clinical trials.ConclusionsThe current literature supports limited use of GI decontamination of the poisoned patient