PubMed · 13284459
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
A A CAIRO. 1956. Hyperchloremic acidosis.. https://pubmed.ncbi.nlm.nih.gov/13284459/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Benzodiazepine poisoning causes coma and respiratory depression. Our objective was to determine whether, and to what extent, arterial blood gas disturbances correlated with blood or cerebral kinetics of midazolam. A 160 mgkg(-1) single dose of midazolam was infused intravenously over 20 min in catheterized male Sprague-Dawley rats. Midazolam kinetics was simultaneously determined in plasma and brain using striatal microdialysis. Midazolam concentrations were measured using a high-performance liquid chromatographic assay with ultraviolet detection. Midazolam (160 mgkg(-1)) reproducibly induced deep coma with respiratory acidosis. Plasma midazolam kinetics was well described by a bi-exponential model, with an elimination half-life of 6.4+/-1.8 h. The striatal dialysate concentration peaked at 50.0+/-8.9 min after the end of infusion, with a significant delay to peak concentration compared to plasma. Respiratory depression, assessed by the elevation in PaCO2, was more closely correlated with midazolam striatal dialysate rather than plasma kinetics. These results suggest a central mechanism for midazolam respiratory effects at toxic doses in rats. In conclusion, our study showed a delayed onset in peak PaCO2 and pH effects after the slow infusion of a toxic dose of midazolam in rats. The effects on arterial blood gases were better correlated with midazolam striatal concentrations than with plasma concentrations. This study may contribute to better understanding of benzodiazepine-induced respiratory depression in poisonings.
The transcription factor HIF-1alpha has been identified as a key regulator in the cellular and systemic response to hypoxia. Because hypoxia is frequently associated with acidosis, like in ischemia or tumour growth, we studied the impact of acidosis on the expression of the HIF-1alpha and HIF-2alpha proteins and that of the three HIF target genes carbonic anhydrase-9 (CA-9), glucose transporter-1 (Glut-1) and erythropoietin (EPO). Since the HIF-prolyl hydroxylases (PHD) modulate cellular HIF-alpha protein levels we also investigated changes in PHD mRNA expression under hypoxia and acidosis. HIF-1alpha immunoblots revealed, depending on the cell line investigated, a moderate induction of HIF-alpha protein levels by acidosis in normoxia (Hep3B cells) or hypoxia (HeLa cells). Concordantly, the activity of HIF-driven luciferase reporters was slightly enhanced at pH 7.0. In contrast, HIF target genes exhibited divergent responses to acidosis: basal and hypoxia-induced CA-9 mRNA levels were further increased, whereas hypoxic EPO mRNA induction was attenuated, and Glut-1 mRNA levels were not altered by acidosis. Except from a small increase of hypoxia-induced PHD3 mRNA levels in HeLa cells, there was also no significant effect of acidosis on PHD expression. In conclusion, albeit HIF protein levels slightly induced by acidosis and the inconsistent regulation of HIF target genes under acidosis suggest additional, yet unidentified pH-sensitive factors to be involved in the regulation of these genes.
Methanol remains to be a major public and environmental health hazard. Formic acid is the toxic metabolite responsible for the metabolic acidosis observed in methanol poisoning in humans, in non-human primates and in folate-depleted rodents. Cytochrome oxidase inhibition by formate leads to lactic acid accumulation, which contributes significantly to metabolic acidosis. Toxic effects in human beings are characterized by formic acidemia, metabolic acidosis, ocular toxicity, nervous system depression, blindness, coma and death. Elimination of formate is one of the principles of management in methanol poisoning. Hemodialysis facility is not readily available in all the places, in developing countries like India. Formate dehydrogenase (EC 1.2.1.2) acts directly over formate and converts formate into CO(2) in the presence of NAD. Effect of single intravenous bolus infusion of formate dehydrogenase, obtained from Candida boidinii; in methanol-intoxicated folate deficient rat model was evaluated. Folate depletion induced by methotrexate (MTX) treatment. Carbicarb (Carb) (equimolar solution of sodium carbonate and sodium bicarbonate) was used to treat metabolic acidosis. Experimental design consists of seven groups, namely Saline control, methanol control, MTX control, Enzyme control, MTX-methanol control, MTX-methanol-Carb and MTX-methanol-Carb-Enz group. Male wistar rats treated with MTX (0.3mg/kg) for a week, were injected (i.p.) with methanol (4 gm/kg), 12h latter, Carbicarb solution was infused, following this enzyme was infused (i.v.) in bolus. Blood samples were collected every 15 min for an hour from the cannulated left jugular vein and blood methanol, formate were estimated, respectively, with HPLC and fluorimetric assay. Blood pH, blood gases pO(2), pCO(2) and bicarbonate were monitored with blood gas analyzer in order to evaluate acid base status of the animal. Results obtained show that there is significant elimination of formate within 15 min. It may be concluded that single bolus infusion of formate dehydrogenase facilitates fast removal of formate, a highly toxic metabolite in methanol poisoning.