A simple, noninvasive procedure was developed to monitor glucuronidation and sulphation in patients using paracetamol as the test drug. Urinary paracetamol and its metabolites were determined by UV absorption and electrochemical detection after separation by HPLC. The metabolite to paracetamol ratio (M/P) was used as an approximation of the partial clearance due to metabolite formation. In 14 healthy volunteers, all nonsmokers without medication, M/P was 18 +/- 5 for glucuronides and 12 +/- 4 for sulphate esters. The test was validated in patients treated with enzyme inducers. In 10 patients with epilepsy given phenytoin 0.3 g/day, and in 10 patients with tuberculosis treated with rifampicin 0.6 g/day, the M/P value for glucuronidation was significantly increased to 41 +/- 11 and 35 +/- 7, respectively. In contrast, M/P values for sulphation were not significantly different from untreated controls. In 9 heavy smokers (about 40 cigarettes/day) M/P values for glucuronidation were also significantly increased to 33 +/- 11. However, in 4 moderate smokers (about 10 cigarettes/day) no significant increase was found. The results suggest that in man glucuronidation of paracetamol is inducible both by phenobarbital- and 3-methylcholanthrene-type inducers. Monitoring the ratios of various urinary paracetamol conjugates/paracetamol may be useful as a new tool for the evaluation of factors determining glucuronide and sulphate ester formation in man.
The pathogenic role of hyperlipidemia in sudden hearing loss (SHL) was examined in a prospective study. Twenty-five patients (14 males, 11 females; age range, 23-59 years) with a first event of SHL (group I) were compared with 9 patients (4 males, 5 females; age range, 28-86 years) with a repeated event of SHL (group II). Audiological examination revealed different types of SHL in group I vs group II: high-frequency loss, 76% vs 22%; low-frequency loss, 12% vs 22%; pancochlear hearing loss, 12% vs 56%. Serum lipid patterns and atherogenic risk factors in both groups were not different and corresponded to lipid patterns in the average population. These findings indicate that both hyperlipidemia and atherogenic risk factors are not of major pathological importance in SHL.
The quantum yields of bleaching for two artificial pigments, bovine opsin combined with (3R)-3-hydroxy retinal or (3R,S)-3-methoxy retinal, were determined in comparison to the value for regenerated bovine rhodopsin. Regeneration of the visual pigments was performed by incubation of 3-[(3-Cholamidopropyl)-dimethylammonio]-2-hydroxy-1- propanesulfonate (CHAPSO)-solubilized opsin with the 11-cis isomers of retinal and the respective retinal derivatives. The extinction coefficients of the pigments in CHAPSO were determined to 35,000 M-1 cm-1 (native rhodopsin), 35,300 M-1 cm-1 (regenerated rhodopsin) and 34,500 M-1 cm-1 (3-OH retinal opsin). With respect to rhodopsin (lambda max: 500 nm), the pigments carrying the substituted chromophores exhibit blue shifted absorbance maxima (3-hydroxy and 3-methoxy retinal opsin: 488 nm). In parallel experiments under absolutely identical conditions we find related to the value of CHAPSO solubilized rhodopsin (identical to 1) a quantum efficiency of bleaching for the 3-hydroxy pigment of 1.2.
A group of eleven subjects with Gilbert's syndrome was characterized by conventional tests and determination of bilirubin and its conjugates in plasma by alkaline methanolysis and thin layer chromatography. After a 1 g dose of paracetamol h.s. the drug and its metabolites were measured by high performance liquid chromatography (HPLC) in the overnight 8-h urine sample. The amounts of paracetamol and of its metabolites recovered in urine were almost identical with those found in the control group (n = 10). The glucuronide:paracetamol ratio, which is considered to be an index of glucuronidation, was not correlated with the fraction of bilirubin present in plasma as glucuronides. These data do not suggest that in subjects with Gilbert's syndrome therapeutic doses of paracetamol are associated with an increased risk for hepatic or systemic toxicity.
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