Effect of ethanol on the urinary excretion of cyclohexanol and cyclohexanediols, biomarkers of the exposure to cyclohexanone, cyclohexane and cyclohexanol in humans.

OBJECTIVES: This study explored the acute effect of ethanol (EtOH) on the urinary excretion of cyclohexanol (CH-ol), 1,2- and 1,4-cyclohexanediol (CH-diol), biomarkers of exposure to important solvents, and chemical intermediates cyclohexanone (CH-one), cyclohexane (CH) and cyclohexanol. METHODS: Volunteers (5-8 in each group) were exposed for 8 hours either to CH-one, CH or CH-ol vapor at concentrations of about 200, 1000, and 200 mg/m3, respectively, with concomitant ingestion of EtOH (4 14-g doses taken during the exposure). Urine was collected for 72 hours and analyzed for CH-ol and CH-diols using a procedure involving acidic hydrolysis and gas chromatographic determination. RESULTS: The metabolic yields of CH-ol, 1,2-, and 1,4-CH-diol, respectively, in the exposures with EtOH were as follows: 11.3%, 36%, 23% after the exposure to CH-one, 3.1%, 15%, 8% after the exposure to CH, and 6.6%, 24%, 18% after the exposure to CH-ol. [The corresponding values obtained previously in matching experiments without EtOH were as follows: 1.0%, 39%, 18% (CH-one); 0.5%, 23%, 11% (CH); and 1.1%, 19%, 8% (CH-ol).] The excretion curves of the metabolites in the exposures with EtOH were not delayed when compared with the corresponding curves of a comparison group. CONCLUSIONS: The urinary excretion of CH-diols is much less sensitive to EtOH than that of CH-ol. It is recommended to employ CH-diols as useful and more reliable biomarkers of exposure to CH-one, CH and CH-ol in field examinations.

1,2- and 1,4-Cyclohexanediol: major urinary metabolites and biomarkers of exposure to cyclohexane, cyclohexanone, and cyclohexanol in humans.

The metabolism and toxicokinetics of cyclohexane (CH) and cyclohexanol (CH-ol), important solvents and chemical intermediates, were studied in volunteers after 8-h periods of inhalation exposure at concentrations of 1010 and 236 mg m(-3), respectively (occupational exposure limits: CH, 1050 mg m(-3); CH-ol, 200 mg m(-3)). Of the dose of absorbed parent compounds, the yields of urinary CH-ol and 1,2- and 1,4-cyclohexanediol (CH-diol) were 0.5%, 23.4%, and 11.3%, respectively, after exposure to CH and 1.1%, 19.1%, and 8.4%, respectively, after exposure to CH-ol as determined by a gas chromatography method involving hydrolysis of glucuronide conjugates. The metabolic patterns of CH and CH-ol were very similar to that of cyclohexanone (CH-one) studied in the laboratory previously. For all three compounds, peak excretion of CH-ol occurred at the end of the exposure period, after which it decayed rapidly. Excretion curves of 1,2- and 1,4-CH-diol reached maximal values within 0-6 h postexposure, with subsequent elimination half-lives being 14-18 h. The rate-limiting step in the elimination of CH compounds from the organism is renal clearance of CH-diols. Determination of CH-diols in end-of-shift urine samples is recommended as a useful new method of biomonitoring of CH, CH-ol, and CH-one at the workplace. However, due to accumulation of CH-diols in the body during repeated exposure, quantitative relationships between the exposure and the level of CH-diols have to be adjusted according to the day of sampling during the working week.

[Comparison of the effects of omega-3 polyunsaturated fatty acids and Olbetam (Acipimox) in the treatment of hypertriglyceridemia]. / Srovnání úcinku polyenových mastných kyselin rady omega-3 a preparátu Olbetam (Acipimox) v lécbe hypertriglyceridémie.

BACKGROUND: Hypertriglyceridaemia associated with low HDL-concentrations is considered an independent risk factor of ischaemic heart disease. The drug of choice in this disorder is nicotinic acid. The aim of the presented work was to compare the hypolipidaemic effect of fish oils rich in omega-3 fatty acids (Activepa 30-TGR, Hydromartens, Norway) with a nicotinic acid derivative, acipimox (Olbetam, Farmitalia Carlo Erba, Italy). METHODS AND RESULTS: The preparations were administered for a three-week period to two groups of patients with hypertriglyceridaemia and low HDL cholesterol levels. The groups had comparable body weights and baseline parameters of lipid metabolism. In the group treated with Olbetam (750 mg/day), 17x hyperlipoproteinaemia type IV and 6x IIB) after treatment significant changes of the following parameters were recorded: triglycerides (-18%; P < 0.001), HDL cholesterol (+19%; P < 0.01), HDL2 and HDL3 cholesterol (+33%; +14%; P < 0.001, P < 0.01), apo B (+25%; P < 0.01), apo A-I (+7%; P < 0.01), ratio of apoB/A-I (+17%; P < 0.01). Furthermore, there was s drop of the atherogenic index (total cholesterol/HDL cholesterol) by 22% (P < 0.001). In the group of subjects (17x type IV and 8x type IIB) whose diet was enriched with omega-3 fatty acids (3.5 g/day), the following parameters changed significantly: triglycerides (-44%; P < 0.001), the atherogenic index (-23%; P < 0.001), HDL cholesterol (+11%, P < 0.01), HDL2 and HDL3 cholesterol (+13%, +17%; P < 0.01, P < 0.05). Changes of apo B, apo A-I concentrations and their ratios were not significant. Comparison of the effect of the two preparations on the investigated parameters revealed a more marked rise of the HDL cholesterol (P < 0.05), apo B (P < 0.01) concentrations and the apo B/-A-I ratio (P < 0.05) during Olbetam treatment. As to the action of the two preparations on further investigated parameters (total and LDL-cholesterol), no significant differences found. CONCLUSIONS: The assembled results indicate that enrichment of the diet with fish oil rich in omega-3 fatty acids has a hypolipidaemic effect comparable to acipimox. It is thus feasible to use fish oils as a drug of first choice in the treatment of hypertriglyceridaemia associated with a reduction of HDL cholesterol concentration.

Uptake, metabolism and elimination of cyclohexanone in humans.

The metabolism and toxicokinetics of cyclohexanone (CH-one), an important solvent and chemical intermediate, have been studied in volunteers during and after 8-h exposures to CH-one vapour at a concentration of 101, 207 and 406 mg.m-3. The pulmonary ventilation in these experiments was typically 11 l.min-1 and retention in the respiratory tract was 58%. After exposure to CH-one, 207 mg.m-3, the metabolic yields of cyclohexanol (CH-ol), 1,2- and 1,4-cyclohexanediol (CH-diol) as determined in urine by a gas chromatographic method involving hydrolysis of glucuronide conjugate were 1.0% +/- 0.3%, 39% +/- 5% and 18% +/- 2% (n = 8), respectively. Peak excretion of CH-ol was achieved at the end of the exposure period, after which it decayed rapidly. Elimination of 1,2- and 1,4-CH-diol reached maximum values a few hours following exposure, with subsequent elimination half-times of 16 +/- 2 and 18 +/- 4 h, respectively. Repeated exposure to CH-one vapour (around 200 mg.m-3) for five consecutive days (8 h/day) resulted in cumulative excretion of CH-diols. The permeation rate of CH-one liquid through the skin was 0.037-0.069 mg.cm-2.h-1 (n = 3), indicating that the contribution of percutaneous absorption to total CH-one occupational intake is of minor importance. CH-diols are recommended as biomarkers of exposure to CH-one.

[The importance of plasma lipids and apolipoproteins in the assessment of risk of myocardial infarction in the most common types of primary hyperlipoproteinemias]. / Význam plazmatických lipidu a apolipoproteinu pri stanovení rizika infarktu myokarkdu u nejcastejsích typu primárních hyperlipoproteinémií.

In a group of 60 men after myocardial infarction (IM) with primary hyperlipoproteinaemia (HLP), type IIA, IIB and IV the authors revealed on comparison with a control group of 71 men with similar types of HLP where ischaemic heart disease (IHD) was not detected, significantly higher concentrations of total plasma cholesterol (TC), low density lipoproteins (LDL-C), apolipoprotein (apo)B in LDL; in the hyperlipidaemic subjects after IM the concentration of HDL-C was significantly lower as well as the ratio of cholesterol and apo-B in the LDL fraction. In patients with hypercholesterolaemia (HLP IIA and IIB) for estimation of the risk of IHD LDL-C, HDL-C and apo-B in LDL are useful. In patients with hypertriglyceridaemia (HLP IIB and IV) subjects with a history of IM have in addition to a higher concentration of apo-B in LDL a lower ratio of cholesterol to apo-B in LDL and in those with HLP IV also a lower plasma concentration of apo-A-I. By the discriminating function the variable of which is in HLP IIB the apo-B concentration in LDL and in HLP IV apo-B in LDL and apo-A-I in plasma in HLP IIB 77.8% subjects and in HLP IV 82.9% subjects with an increased risk of IHD can be detected.

[Beta-sitosterol in the treatment of hypercholesterolemia]. / Beta-sitosterol v lécbe hypercholesterolémie.

A group of 28 patients with primary hyperlipoproteinaemia [19X lipoprotein (LP) type IIA, 8X type IIB and 1X a normolipidaemic patient with concurrent hyperapoB lipoproteinaemia] were given for a period of three weeks a dietetic preparation containing phytosterols - 12 g/day. This led to a significant drop of total cholesterol and LDL-cholesterol in plasma. The cholesterol concentration in HDL and both its fractions increased, the differences however were not significant. The triglyceride levels did not change. There was a significant drop of the apolipoprotein B (apo-B) concentration in LDL, the apo-A-I in plasma did not change. There was a significant drop of atherogenic indexes TC/HDL-C, LDL-C/HDL-C and apo-B/-A-I. During investigation of the LCAT activity the authors observed a significant rise of the fractional esterification rate associated with a highly significant drop of the free cholesterol concentration in plasma as a result of treatment. Discrimination analysis of parameters of the lipoprotein metabolism and the patients' body weight before treatment helps to assess a function by means of which it is possible in 92.3% of the subjects to predict the success of treatment before the administration of beta-sitosterol.