Study of blood and brain lithium pharmacokinetics in the rat according to three different modalities of poisoning.

Lithium-induced neurotoxicity may be life threatening. Three patterns have been described, including acute, acute-on-chronic, and chronic poisoning, with unexplained discrepancies in the relationship between clinical features and plasma lithium concentrations. Our objective was to investigate differences in plasma, erythrocyte, cerebrospinal fluid, and brain lithium pharmacokinetics using a multicompartmental approach in rat models mimicking the three human intoxication patterns. We developed acute (intraperitoneal administration of 185 mg/kg Li2CO3 in naive rats), acute-on-chronic (intraperitoneal administration of 185 mg/kg Li2CO3 in rats receiving 800 mg/l Li2CO3 in water during 28 days), and chronic poisoning models (intraperitoneal administration of 74 mg/kg Li2CO3 during 5 days in rats with 15 mg/kg K2Cr2O7-induced renal failure). Delayed absorption (4.03 vs 0.31 h), increased plasma elimination (0.65 vs 0.37 l/kg/h) and shorter half-life (1.75 vs 2.68 h) were observed in acute-on-chronically compared with acutely poisoned rats. Erythrocyte and cerebrospinal fluid kinetics paralleled plasma kinetics in both models. Brain lithium distribution was rapid (as early as 15 min), inhomogeneous and with delayed elimination (over 78 h). However, brain lithium accumulation was more marked in acute-on-chronically than acutely poisoned rats [area-under-the-curve of brain concentrations (379 ± 41 vs 295 ± 26, P < .05) and brain-to-plasma ratio (45 ± 10 vs 8 ± 2, P < .0001) at 54 h]. Moreover, brain lithium distribution was increased in chronically compared with acute-on-chronically poisoned rats (brain-to-plasma ratio: 9 ± 1 vs 3 ± 0, P < .01). In conclusion, prolonged rat exposure results in brain lithium accumulation, which is more marked in the presence of renal failure. Our data suggest that differences in plasma and brain kinetics may at least partially explain the observed variability between human intoxication patterns.

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. Sample analysis was conducted using two techniques; ion chromatography with suppressed conductivity and negative ion electrospray ionization with MS detection or with gas chromatography using electron impact ionization or methane negative chemical ionization with MS detection. Stable-isotope-labeled analogs of each analyte were employed as quantitative internal standards in the assays.

Cerebrospinal fluid findings in cattle with central nervous system disorders: a retrospective study of 102 cases (1990-2008).

BACKGROUND: Cerebrospinal fluid (CSF) analysis is routinely used to aid in the diagnosis of central nervous system (CNS) disease in animals. There is little comprehensive information available on the diagnostic utility of CSF analysis in cattle. OBJECTIVES: The purpose of this retrospective study was to review the characteristic CSF findings of specific CNS diseases in cattle. METHODS: Medical records of cattle in which CSF analysis had been performed between 1990 and 2008 were reviewed. Cattle were included in the study if they had a confirmed diagnosis of CNS disease (based on clinical signs, laboratory testing, and/or histopathologic results). Cattle were categorized as having infectious or noninfectious causes of CNS disease and subgrouped based on specific disease diagnosis. CSF results were summarized and compared using nonparametric statistical tests. RESULTS: Data from 102 cattle, mostly female Holsteins, were included in the study. Bacterial infections, particularly listeriosis and neonatal meningitis, were the most common cause of CNS disease. Neonatal meningitis was characterized by a marked, predominantly neutrophilic, pleocytosis. Mild mononuclear pleocytosis was typical of listeriosis, but was also seen with abscesses, viral infections, salt poisoning, and trauma. Variable CSF results were seen in cattle with otitis-related meningitis and thromboembolic meningoencephalitis. CSF results were usually normal with toxic, metabolic, degenerative, and neoplastic disorders. CONCLUSIONS: CSF analysis is a useful adjunctive test for the diagnosis of CNS diseases in cattle. When interpreted together with signalment and clinical signs, CSF results can assist clinicians in the antemortem diagnosis of specific bovine CNS disorders.

[Crystallization of cerebrospinal fluid in cases of death from ischemic heart disease and ethanol poisoning]. / Kristallizatsiia spinno-mozgovoi zhidkosti v sluchaiakh smerti ot ishemicheskoi bolezni serdtsa i otravleniia étilovym alkogolem.

Crystallographic analysis of the cerebrospinal fluid (CSF) was carried out in 18 cases of death from coronary disease and 19 cases of death from ethanol poisoning. The crystallograms were evaluated visually and by the stereoscopic picture. Specific features of the CSF crystal colonies growth in subjects dead from the above conditions are determined.

Changes in phenytoin concentrations in blood and cerebrospinal fluid caused by direct hemoperfusion in a patient intoxicated with phenytoin.

We performed direct hemoperfusion (DHP) 5 times on a patient with consciousness disorder and phenytoin intoxication. We then measured the phenytoin concentrations in her cerebrospinal fluid (CSF) and blood at various times. After the first DHP session, consciousness began to improve, and it normalized after the fourth DHP session when the blood concentration of phenytoin had decreased from 54.0 microg/ml to 16.5 microg/ml. The average plasma phenytoin elimination rate of DHP was 18.0% over 120-180 min. The concentration of phenytoin in the CSF decreased as that in the blood was lowered by DHP. The average reduction rate of phenytoin in the CSF after a DHP session was 23.7%, which was similar to the rate of elimination from the blood. The CSF/blood phenytoin ratio was 0.17, and no marked changes were detected before or after a DHP session.

[Monoamine metabolites and cyclic nucleotides in the cerebrospinal fluid of patients with bismuth or mercury poisoning]. / Monoaminmetabolite und zyklische Nukleotide des Liquor cerebrospinalis bei Wismut- und Quecksilber-Encephalopathien.

The central metabolism of dopamine, serotonin, cyclic AMP and cyclic GMP was studied by use of the probenecid test in three patients with bismuth encephalopathy and in one patient with mercury encephalopathy. The accumulation of HVA and of cGMP in the cerebrospinal fluid was depressed during the acute phase of bismuth encephalopathy with severe hyposomnia, while it was increased in a patient with regression of clinical symptoms and normal in a patient with more advanced recovery. The patient with chronic mercury poisoning showing a severe cerebellar ataxia and rigidity had an almost complete suppression of HVA accumulation and an increase of cGMP accumulation. No pronounced differences of 5-HIAA and cAMP behavior were found. It is concluded that the central metabolism of dopamine and of cGMP is severely affected in bismuth and mercury encephalopathies.

[Study of calcium and magnesium in cerebrospinal fluid and its' relation to different neurological diseases (author's transl)]. / Estudio de calcio y magnesio en líquido cefalorraquídeo en diversas enfermedades neurológicas.

Calcium and magnesium have been measured in cerebrospinal fluid by atomic absorption spectrophotometry in children. The normal values on 194 C.S.F., obtaining for the calcium x: 5.24 mg. % and s: +/- 0.378 mg. % [50--56 % lower than serum values] and for magnesium x: 2.64 mg. % and s: +/- 0.155 mg. % [19--33 % higher than serum values] are found. Higher values of calcium at birth and on the first year of life and no differences with magnesium are noted. Applying the t-test, between normal values obtained and the different pathological entities, authors find singificant differences on the level of calcium, finding higher values on the following diseases: dehydration by diarrhoea, poliomyelitis, anoxy, tumours, bacterial meningitis. Magnesium showed values significantly higher in dehydration by diarrhoea and epilepsy, and values significantly lower on febrile convulsions and virical and bacterial meningitis.

Methyl alcohol poisoning III. Ocular toxicity.

The ocular toxicity of methyl alcohol has been investigated in six rhesus monkeys. All the animals developed fundus changes within 43 to 171 hours after its ingestion. The only fundus lesion seen was optic disc edema and associated changes, usually of a marked degree. Fluorescein fundus angiography confirmed the findings. The retinal and choroidal circulations, including the retinal capillary bed, were normal. Ophthalmoscopically and angiographically, optic disc edema in methyl alcohol poisoning was indistinguishable from that seen in raised intracranial pressure, except that no increased intracranial pressure was observed. It is postulated that optic disc edema in methyl alcohol poisoning is due to an axoplasmic flow stasis.