M. P. C. Hectors

Influence of Age, Intestinal Transit Time, and Dietary Composition on Fecal Bile Acid Profiles in Healthy Subjects

Bacterial transformation of bile acids is possibly involved in colorectal carcinogenesis. In several epidemiological studies, the secondary bile acid concentration in feces is related to the incidence of colonic cancer. However, data on fecal bile acids in case-control studies are conflicting. We investigated the influence of age, intestinal transit time, and dietary composition on fecal bile acid profiles in healthy subjects of three different age groups (mean ages 22, 48, and 67 years). Fecal bile acids were analyzed by gas-liquid chromatography. The concentration of the major secondary fecal bile acids increased with advancing age and was significantly higher in elderly subjects, compared to young adults. The concentration in middle-aged persons was intermediate. Analysis of dietary constituents showed that the fat intake in the three groups was comparable. The dietary fiber intake in elderly subjects was significantly lower than in the other two groups. The former group did excrete less dry fecal material compared to both other groups. Dietary fiber intake was negatively correlated with the total bile acid concentration. Probably, a decrease in dietary fiber intake results in higher fecal bile acid concentrations with advancing age. From the findings of this study, it is obvious that matching for age is important when case-control studies concerning the role of fecal bile acids in colorectal carcinogenesis are conducted.

Effects of a standardized wheat bran preparation on biliary lipid composition and bile acid metabolism in young healthy males

Abstract. The effects of adding bran to the normal diet on biliary lipid composition and bile acid metabolism in a group of young healthy males was studied. A chemically standardized coarse wheat bran product, with serum lipid lowering properties, in a dose of 0–5 kg‐1 body weight per day was used. Bran feeding for 4 or 8 weeks did not change biliary lipid and biliary bile acid composition. Faecal bile acid and neutral sterol composition was similar before and after 8 weeks of bran. Bile acid kinetics, measured by double isotope dilution after simultaneous injection of [3H]cholic acid and [14C]deoxychoIic acid, showed only minor differences before and during bran ingestion. The most surprising finding was an increase in 7α‐dehydroxyl‐ation fraction (input of deoxycholic acid divided by synthesis of cholic acid) in six out of seven subjects after 4 weeks of bran and in all four subjects after 8 weeks of bran. In conclusion, the bran product we used is not effective in lowering the biliary cholesterol saturation in healthy young males. Nor does it reduce deoxycholate input in our subjects even after 8 weeks of bran.

Serum versus heparinized plasma for alanine aminotransferase and aspartate aminotransferase of normal individuals.

The influence of heparin on the estimation of aminotransferases was investigated in a reaction medium containing phosphate or Tris buffer. Heparin scarcely affects the ASAT determination, but the ALAT activity in plasma is about 70% of the activity in serum, when the enzyme determination is carried out in Tris buffer. There exists a lag phase due to which the decrease in absorbance with the incubation time is nonlinear. When the Tris buffer is omitted, the same lag phase is observed in the ALAT determination. This lag phase is not caused by the indicator enzyme LDH. Addition of phosphate to the incubation medium without any buffer abolishes this lag phase. The possibility exists that heparin influences the structure of the proteins present in plasma and that these proteins, in their turn, decrease the enzymatic activity of ALAT.

Stability studies of ubiquinol in plasma

Background: Ubiquinol is a sensitive redox marker in the first line of the antioxidative defence mechanism and is increasingly being measured in oxidation studies. Because of its apparent instability during storage and processing, we compared various storage conditions. Method: Blood was collected from three volunteers into tubes containing EDTA; it was then separated at 4°C and cryopreserved with saccharose (final concentration 6 g/L). Aliquots were stored with or without glutathione or butylated hydroxytoluene at -20°C and -80°C. Results and conclusion: Ubiquinol in samples stored at -20°C was not stable; however, it was stable when stored at -80°C, even without addition of antioxidant. By contrast, α-tocopherol was stable under all conditions studied.

Does treatment with beta-adrenergic blocking agents cause a decrease in beta2-adrenoceptor affinity?

SummaryThe effect of β-adrenoceptor antagonists (BAAs) differing in lipophilicity and partial agonist activity (PAA), and a full agonist, on the dissociation constant for [125I]-(−)- iodocyanopindolol binding to β2-adrenoceptors (KD) has been investigated.Twelve healthy, normotensive male volunteers (mean age 22.3 y) were treated with different BAAs according to a cross-over design. The drugs used were propranolol (highly lipophilic BAA, no PAA), pindolol (moderately lipophilic BAA, strong PAA), dilevalol (highly lipophilic BAA, weak PAA) and salbutamol (full agonist). Before and after a single dose and an 8 day course of one of the drugs, blood pressure and the β2-adrenoceptor characteristics of mononuclear leukocytes (MNL) were determined. Between the treatment periods, there was a washout interval of 14 days.All BAAs decreased the blood pressure, but only propranolol lowered heart rate. Treatment with salbutamol decreased the diastolic and increased the systolic blood pressure and heart rate. Three hours after the single dose of any of the BAAs, a more than 2-fold increase in KD was observed, and the increase became larger after 8 days of administration (up to 3.7-fold increase). In contrast, no effect on KD was observed after treatment with salbutamol. BAAs with PAA and salbutamol induced a 30% decrease in β2-adrenoceptor density.It is concluded that treatment with BAAs, irrespective their lipophilicity or PAA, induces a decrease in the affinity of MNL β2-adrenoceptors for antagonists. This phenomenon may help to explain the contradictory relationship between the kinetics and dynamics of BAAs.