High density lipoprotein cholesterol and alcohol consumption in a French male population.

The mean high density lipoprotein cholesterol (HDL-C) level in a sample of 640 apparently healthy male employees of a branch of the Paris civil service, aged 22-56, appears high (between 56.5 and 61.8 mg/dl depending on age groups). A positive relationship between HDL-C and alcohol intake is observed only after age 30, but is revealed in all age groups when the triglyceride level is taken into account. Differences in drinking habits by age may explain this. The moderate effect of alcohol intake on HDL-C is not sufficient to account for the high mean levels observed.

Relationship between sex hormones and haemostatic factors in healthy middle-aged men.

Associations of plasma testosterone and estradiol with some haemostatic factors (factor VII activity, fibrinogen, antithrombin III and alpha 2-antiplasmin) were cross-sectionally examined in 251 healthy, middle-aged men participating in the Paris Prospective Study II on risk factors for ischaemic heart disease. Testosterone levels were negatively correlated to factor VII activity and alpha 2-antiplasmin, the main inhibitor of fibrinolysis. No association was found either between testosterone levels and both fibrinogen and antithrombin III, or between estradiol levels and the set of haemostatic variables. The associations between testosterone and both factor VIIc and alpha 2-antiplasmin were independent of HDL-cholesterol, LDL-cholesterol, triglycerides, smoking, alcohol, body mass index and blood pressure. These results suggest that low circulating testosterone levels might be associated with a hypercoagulability state and therefore could contribute to an increased risk of IHD.

Acinar cells are target cells for androgens in mouse submandibular glands.

The variable coding sequence (VCS) multigene family encodes diverse salivary proteins, such as the SMR1 prohormone and the PR-VB1 proline-rich protein in the rat. In situ hybridization was used to study the cell-specific expression of two new mouse VCS genes, Vcs1 and Vcs2. We show that the Vcs1 transcripts, which code for a proline-rich protein, MSG1, are highly abundant in male and female parotid glands, in which they are specifically detected in acinar cells. No expression was seen in the submandibular or sublingual glands. In contrast, Vcs2 transcripts were found only in the acinar cells of the submandibular glands (SMGs) of male mice, in which they are expressed in response to androgens. Expression was found to be heterogeneous within acinar structures. No Vcs2 transcripts were detected in the SMGs of females or castrated males by Northern blot, RNase protection, or in situ hybridization. Androgen administration to females or castrated males induced expression at a level comparable to that of intact males. The Vcs2 gene is the first example of a mouse androgen-regulated gene that is expressed in SMG acinar cells. This result, in addition to our previous observation on SMR1 expression in rats, demonstrates that both acinar cells and granular convoluted tubule (GCT) cells are target cells for androgen action in rodent SMG.

Phalloidin hepatotoxicity in rats in vivo. Effect of a sympatholytic agent: propranolol.

Phalloidin, one of the main toxins of Amanita phalloides, induced hepatotoxicity in female Wistar rats at 0.9 mg/kg dose i.p. Biliary secretion was selectively inhibited after 3h, but was restored after 24 h. Phalloidin also induced a cytolytic lesion, but not a fatty liver, as in alpha-amanitin intoxication. Propranolol pretreatment (30 min prior to phalloidin injection) did not afford protection against hepatotoxicity, but increased alkaline phosphatase, 5'-nucleotidase and aminotransferase activities.

Enzyme induction with high doses of rifampicin in Wistar rats.

Hepatic microsomal enzyme activities were determined in female Wistar rats after 1 and 8 days of oral administration of high doses of rifampicin (RFP) (400 mg/kg/day). After 8 days, the level of cytochrome P-450 doubled and the activities of NADPH-cytochrome c reductase and benzphetamine N-demethylase were significantly increased. The observed changes in enzymic activities are consistent with the possibility that RFP induces a special form of cytochrome P-450, responsible for the metabolism of the antibiotic (demethylation and reduction of rifampicin quinone). Considering the role of the endoplasmic reticulum in lipid metabolism, the inducing activity of RFP might also contribute to the observed accumulation of lipids in the liver.

Time course of cytochromes P450 decline during rat hepatocyte isolation and culture: effect of L-NAME.

The present work describes an isozyme-related effect of collagenase perfusion on hepatocyte microsomal cytochrome (CYP)-dependent monooxygenase activities: CYP 1A1/2-, 2B1/2-, 3A1/2- and 2E1-dependent activities in microsomes from rat hepatocytes after isolation were about 60% of that of liver microsomes, and CYP 4A1-dependent activity was equivalent to liver microsomes. In contrast, the microsomal protein content of the various CYP isoforms was not affected by hepatocyte isolation. This is in accordance with the hypothesis of CYP inactivation during the process of hepatocyte isolation by collagenase digestion. L-NAME (1 mM) was found unable to protect from the decline of CYP-dependent monooxygenase activities following hepatocyte isolation. It is possible that the decrease in glutathione peroxidase activity observed in the presence of L-NAME, namely depression of defense against peroxynitrite, could counteract the beneficial effect of L-NAME on nitric oxide synthesis inhibition. The present work also shows that L-NAME could not avoid the progressive, isoform-specific, most probably turnover-related, decline of CYP proteins and related monooxygenase activities in cultured hepatocytes. Dysregulations in the mechanisms of CYP expression in rat hepatocyte cultures, presently unknown but nitric oxide independent, thus appear to occur in cultured rat hepatocytes.

Alcohol consumption and the duration of systolic time intervals in middle-aged men.

In a general population of middle-aged men, there was a decrease in cardiac preejection period and in the ratio of preejection period to left ventricular ejection time with an increase in lifetime alcohol consumption. An increase in myocardial contractility with increased alcohol consumption is suggested.

Rifampicin and isoniazid increase acetaminophen and isoniazid cytotoxicity in human HepG2 hepatoma cells.

Acetaminophen (APAP) induced a concentration-dependent (0-30 mM) cytotoxic effect in human HepG2 hepatoma cells which was significantly increased when intracellular reduced glutathione (GSH) content was decreased. The cytotoxic effect of APAP (0-30 mM) was significantly lower in a day 3-treated compared to day 1-treated HepG2 cells. A 3-day preincubation of HepG2 cells with 5 microM 3-methylcholanthrene (3MC), 50 microM rifampicin (RFP) or 1 mM isoniazid (INH) significantly increased 15-30 mM APAP cytotoxicity, of about 15-20% for INH and RFP and 35-50% for 3MC. The cytotoxicity of 10 mM APAP was also increased (about 20%) by a 3-day preincubation with INH but was not affected by 3MC and RFP. INH induced a concentration-dependent (0-40 mM) cytotoxic effect in day-1 treated HepG2 cells and not significantly affected by decreases in intracellular GSH concentrations. INH was not cytotoxic in day 3-treated HepG2 cells. A 3-day preincubation of HepG2 cells with 50 mM RFP or 1 mM INH significantly increased 10-40 mM INH cytotoxicity, respectively of about 10% and 10-25%. A 3-day preincubation with 3MC did not modify the cytotoxic effect of INH at these concentrations. This is to our knowledge the first report of increases by INH and RFP of APAP of INH cytotoxicity in vitro in hepatocellular cells of human origin. It is in accordance with clinical observations of severe hepatotoxicity associated with APAP or INH usage in patients receiving multiple drug therapy (INH, RFP) for tuberculosis or in alcoholics.

[Relationship between blood pressure level and different types of alcoholic beverages]. / Relation entre le niveau de pression artérielle et différents types de boissons alcooliques.

The relationship between alcohol consumption (AC) has been repeatedly confirmed. However, the respective contribution of the various types of beverages has not been clearly established. The cross-sectional data of the initial examination of the Paris prospective study II of the GREA, concerning 4547 male civil servants were thus analysed. Among subjects without any antihypertensive medication, systolic (SBP) and diastolic (DBP) blood pressure were positively associated with total AC; the differences between the first and the fifth quintile were respectively 6 and 3 mmHg (p less than 0.01 for wine, beer and spirits consumption). Using a linear combination of wine, beer and spirits consumption significantly improved the prediction of BP, as compared to total AC (p less than 0.001). In the multivariate analysis including age and body mass index (BMI), the consumption of 40 ml of alcohol from beer was associated with an increase of 5.7 mmHg for SBP and 2.6 mmHg for DBP (p less than 0.001). The elevation was 2.3 (SBP, p less than 0.001) and 0.8 mmHg (DBP, p less than 0.01) for wine consumption. Spirits consumption was associated with DBP (1.4 mmHg, p less than 0.001), but not with SBP. In conclusion, a positive relationship was observed with each of the three types of alcoholic beverages studied; however, this association was more pronounced for beer than for the two other beverages.

[Arterial pressure, obesity and fat and alcohol consumption]. / Pression artérielle, corpulence et consommation de graisse et d'alcool.

The baseline data of 2 500 subjects included in the Paris Prospective Study II were used to explore the relationship between the frequency of hypertension and some variables closely linked to the diet. These variables are: body mass, alcohol consumption and the proportion of linoleic acid (C18:2) in the plasma cholesterol esters; the latter variable being used as a marker of dietary intake of linoleic acid. The results show, after adjustment on age and the presence of an antihypertensive treatment, a significant independent relationship between these factors and the frequency of hypertension. The adjusted relative frequency of hypertension is 1, 1.4 and 2.5 in the tertiles of increasing corpulence; 1, 1.2 and 1.7 in the tertiles of increasing alcohol consumption and 1, 0.6 and 0.8 in the tertiles of increasing C18:2. Furthermore, among the 263 subjects belonging simultaneously to the higher tertiles of corpulence and alcohol consumption and to the two lower tertiles of C18:2, the number of hypertensive subjects is 58 (22 p. 100 whereas among the 2 236 remaining subjects, 164 are hypertensives (7 p. 100). These results suggest that hypertension is frequently linked to dietary factors.

[Analysis of the results of the trial where groups have been randomized. The Paris cardiovascular prevention trial (author's transl)]. / Analyse des résultats d'um essai où des groupes ont été randomisés L'essai parisien de prévention cardio-vasculaire.

In a prevention trial, when the randomised units are groups of subjects, the first step in the analysis of the results is to check whether the groups differ, for the variables under study, ie, to test a possible group effect. If this effect is not significant, the results are analysed as if the subjects had been randomised. On the other hand, it this effect is significant, the comparison must be carried out between the groups and no more between the subjects. In the latter case, the loss of efficiency of the randomization of groups instead of the randomization of subjects can be computed. When a group effect is present and the number of subjects in each group differs, the analysis is considerably more complex. In the Paris cardiovascular prevention trial, 160 groups of young men, with variable numbers of subjects in each group have been randomised. The change in weight, blood cholesterol and cigarette consumption after two years of intervention are analysed in the present paper with the methodological principles mentioned above.

[Determination of total serum triiodothyronine in hyperthyroidism: comparison of fluorescence polarization and immunoenzymology]. / Dosage de la triiodothyronine sérique totale dans les hyperthyroïdies: comparaison de la polarisation de fluorescence et de l'immunoenzymologie.

We evaluated the performances of the Abbott fluorescence polarization assay (FPIA) utilizing the TDx system for human total triiodothyronine (T3) in hyperthyroidism. We compared the results with an immunoenzymometric assay (IEA) (Enzymum Test T3 Boehringer-Mannheim). Greatest attention was focused on the diagnosis of hyperthyroidism because detection of subclinical hyperthyroidism is important. The repeatability of the Abbott fluorescence polarization assay was satisfying (m = 8.07 +/- 0.37 nmol.l-1, CV = 4.59%). The reproducibility was tested with Abbott control sera: m = 4.58 +/- 0.53 nmol.l-1 and CV = 11.5 per cent for level M; m = 7.95 +/- 0.66 nmol.l-1 and CV = 8.23 per cent for level H; m = 2.38 +/- 0.39 nmol.l-1 and CV = 16.5 for level L. The correlation of results of the Abbott assay with those of the Boehringer assay was good for samples from hyperthyroid patients. Values for hyperthyroid and euthyroid subjects were resolved slightly better with the Abbott FPIA than with Boehringer IEA. The Abbott total T3 fluorescence polarization assay may have an additional role to play in monitoring thyroid function in patients under iodine treatment (amiodarone) to eliminate a secondary hyperthyroïdism.

[Acute respiratory and circulatory failure. Prognostic value of plasma fibronectin levels]. / Insuffisances respiratoires et circulatoires aiguës. Valeur pronostique du taux de fibronectine plasmatique.

Plasma fibronectin (FNp) concentrations were measured in 63 patients with acute respiratory failure and 28 patients with circulatory failure, using Laurell's electroimmunoassay method. Measurements were made in the acute phase and repeated in the course of the disease. The mean FNp concentration in 20 controls was 262 +/- 59 mg/l. FNp values were normal in the acute phase of chronic obstructive pulmonary disease and in cardiogenic pulmonary oedema. In contrast, they were significantly decreased in adult respiratory distress syndrome and in acute pneumonia, as well as in acute circulatory failure, notably from septic shock. FNp values were also considerably reduced in patients with severe disseminated intravascular coagulation syndrome. Clinical improvement was accompanied by a return to normal of FNp concentrations. The mortality rate was greater in patients with low FNp values than in those with normal values.

Thyroxine-binding prealbumin, overnutrition and apolipoprotein A1.

Thyroxine-binding prealbumin (TBPA) seems to be more useful than other biochemical markers for the detection of subclinical protein-energy malnutrition. Accordingly, one can question whether its sensitivity to nutritional supply could be used in healthy populations for the discrimination of groups with low or high energy intakes; if such were the case, could TBPA serve as an index of overnutrition? In order to answer these questions, we measured TBPA circulating levels in three groups of healthy French subjects from a working population, with relatively low, medium or high levels of energy intake. We also observed the correlations of this protein with nutrient intakes and with some biological parameters related to the general nutritional status of the subjects. The observed figures did not support the hypothesis that TBPA could be used to discriminate healthy subjects with relatively low or high energy intake nor as an index of overnutrition. This study disclosed a positive relation of TBPA with alcohol consumption and related parameters such as body mass index or gamma-glutamyl transferase as well as a negative one with alpha 2-globulin and gamma-globulin. Other investigators have found similar results in chronic alcoholics, surgical patients, or patients suffering from severe illnesses such as cancer. Here, the study population consisted of adult men, neither undernourished nor suffering from any severe pathology and who could not be considered excessive drinkers. Positive relations were also observed between TBPA and apolipoprotein A1 and HDL cholesterol levels, which are negatively associated with coronary heart disease risk.

Ultrastructural changes in the parenchymal liver cells of rats treated with high doses of rifampicin.

Ultrastructural study of hepatic parenchyma was carried out in female Wistar rats after they had received high doses (400 mg X kg-1) of rifampicin for 1, 2, 4, 6 and 8 days. Morphological changes in the endoplasmic reticulum, Golgi apparatus and mitochondria were observed as early as day 1 of intoxication. These changes corroborate the biochemical data available regarding RFP-induced fatty liver.

Accentuation of white phosphorus induced fatty liver by phenobarbitone in male rats compared to female rats.

The possible influence of a potent enzyme inducer, phenobarbitone, on white phosphorus fatty liver, was studied. Pretreatment by phenobarbitone for four days in white phosphorus poisoned rats provoked a decrease in mortality and an increase in hepatic triglycerides (fatty liver) in male rats. The activity of uridine diphosphoglucuronyl transferase (UDPGT), an inducible enzyme, is not modified by this pretreatment in white phosphorus poisoned rats. The accentuation of white phosphorus fatty liver by phenobarbitone in male rats could be explained by an increased hydroxylation of testosterone, thus counteracting the protective effect of this hormone on fatty liver.