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Biomedical subjects

M P Hectors

Publications and source records attributed to M P Hectors.

At least 19 recordsLinked to original sources

Does treatment with beta-adrenergic blocking agents cause a decrease in beta 2-adrenoceptor affinity?

The effect of beta-adrenoceptor antagonists (BAAs) differing in lipophilicity and partial agonist activity (PAA), and a full agonist, on the dissociation constant for [125I]-(-)- iodocyanopindolol binding to beta 2-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 beta 2-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 beta 2-adrenoceptor density. It is concluded that treatment with BAAs, irrespective their lipophilicity or PAA, induces a decrease in the affinity of MNL beta 2-adrenoceptors for antagonists. This phenomenon may help to explain the contradictory relationship between the kinetics and dynamics of BAAs.

Adrenergic beta-Antagonists

Beta 2-adrenoceptor up-regulation in relation to cAMP production in human lymphocytes after physical exercise.

The effect of isotonic bicycle exercise on beta 2-adrenoceptors and cAMP production in lymphocytes was studied. The origin of the newly exposed receptors was studied by measuring radioligand binding in the presence of hydrophylic or lipophylic 'cold' ligands. During exercise beta 2-adrenoceptor density increased from 1207 +/- 144 to 1776 +/- 152 sites/cell (56 +/- 14%). Isoprenaline induced an increase in cAMP synthesis, which was 68 +/- 15% higher than those values measured before the test. Forskolin did not induce a higher increase in cAMP production after exercise. The increase in receptor density seems not to be due to a transfer of internalized receptors to the membrane surface. We conclude that physical exercise induces an up-regulation of beta 2-adrenoceptors on lymphocytes and that these adrenoceptors are functional.

Adult

The relationship between adrenaline and beta 2-adrenoceptors on human lymphocytes.

To study the relation between plasma adrenaline (AD) and noradrenaline (NA) and the beta 2-adrenoceptor number (Bmax) on lymphocytes these variables were measured in the following three groups: a) In 67 normotensive volunteers after a rest period of at least 15 min. b) In 10 essential hypertensive (HT) and 10 age and sex matched normotensive (NT) subjects before and after a standardized bicycle exercise test (BE). c) In 10 bilaterally adrenalectomized females (AF) and 10 healthy age matched females (NF) before and after a mental arithmetic test (MA). Significant correlations were found between AD and Bmax in NT (r = 0.30, P = 0.015) and between the proportional increase in AD and the proportional increase in Bmax after BE (r = 0.60, P less than 0.005). The MA induced elevation of Bmax was blunted after adrenalectomy. All these findings point to a relation between AD and beta 2-adrenoceptor regulation.

Adrenalectomy

The use of a rat-derived microflora for providing colonization resistance in SPF rats.

To obtain a suitable species-specific microflora for a new rat SPF-unit, germ-free WAG/Rij rats were associated with a flora derived originally from selectively decontaminated Cpb: WU (Wistar) rats. Caecal and ileal contents of these rats had been cultured anaerobically (37 degrees C) for 7 days and harvested. This cultured flora was given to germ-free Cpb: SE (Swiss) mice, which were kept in an isolator system and acted as a source of the flora to associate germ-free Wag/Rij rats. In these associated rats, several parameters indicative of the 'quality' of the intestinal microflora were investigated and compared to those in rats with a mouse derived anaerobic microflora. Parameters included relative caecal weight, colonization resistance and the concentration of faecal bile acids. The cultured rat-derived microflora normalized the observed intestinal parameters better than the mouse derived microflora, and provided better colonization resistance. We conclude that culturing of intestinal contents of selectively decontaminated animals can be a useful way to obtain a species-specific donor-microflora which can be used to start new SPF units.

Animals

The influence of stress and cheese-whey on intestinal parameters in mice.

In a mouse model the effects of environmental stress on gastrointestinal parameters and the effects of cheese-whey on the changes induced by stress were studied. Mice were subjected to overcrowding, lack of bedding, overcrowding together with lack of bedding, continuous light, and housing at 30 degrees C. The influence of stress on relative caecal weight, faecal enterobacteriaceae, colonisation resistance (CR), filamentous segmented bacteria in the small intestine, fusiform bacteria in the faeces, and concentration of faecal bile acids was studied. Stress had no influence on relative caecal weight, faecal enterobacteriaceae, and faecal bile acids. Stress did decrease colonisation resistance, presence of segmented filamentous bacteria in the small intestine, and fusiform bacteria in the faeces. Cheese-whey had no positive effect on the microbiological disturbances caused by stress. The number of filamentous segmented bacteria in the small intestine and fusiforms in the faeces decreased by giving cheese-whey.

Animals

The 'normalization' of germ-free guineapigs with host-specific caecal microflora.

Hysterectomy-derived germ-free guineapigs were given colonization-resistant caecal flora from mice (mCRF) or microflora obtained from the caecum of an antibiotic-decontaminated conventional guineapig (gpCRF) and compared with guineapigs raised conventionally with the sow. Body weight and the following intestinal parameters were determined for the groups: colonization resistance (CR) to Escherichia coli, relative caecal weight (RCW), beta-aspartylglycine (faeces), volatile fatty acids (caecum) and bile acids (faeces). mCRF guineapigs showed values quite different from control animals for CR and RCW, indicating the unsuitability of mouse CRF for normalizing guineapigs. In gpCRF guineapigs CR and RCW values were comparable with controls, indicating the suitability of the guineapig flora for normalizing guineapigs. mCRF guineapigs housed with gpCRF guineapigs, showed an improvement in CR and RCW, yielding values found in control animals.

Animals

Elimination of murine viral pathogens from the caecal contents of mice by anaerobic preparation.

The aim of this study was to investigate methods to eliminate pathogenic viral agents while preserving the 'normalizing' properties of the gut microflora of mice. Mouse hepatitis virus A59 (MHV), Reo 3 virus and Theiler GD VII virus were added to the caecal contents of 'normal' mice and following dilution, with or without subsequent culturing, given to germ-free mice. Four weeks later antibody titres against these and other viruses were determined. MHV and Theiler CD VII virus survived dilution but were eliminated during culturing. Reo-virus survived the 10(-1) dilution-culture step. All dilutions and dilution-cultures of caecal contents resulted in 'normalization' in germ-free recipients of the relative caecal weight, percentage faecal fusiform-shaped bacteria, faecal bile acids and colonization of small intestine by segmented filamentous bacteria.

Animals

Intestinal "normalization" of germ-free rabbits with rabbit caecal microflora: effect of dosing regimens.

Hysterectomy-derived germ-free (GF) rabbits were given strictly anaerobic microflora obtained from the caecum of an antibiotic-decontaminated conventional rabbit. One group was given the caecal flora diluted in doe's milk. The second group received caecal flora without doe's milk and administration of the flora was repeated when the animals were given pelleted diet. Body weight and intestinal parameters determined in the two groups of rabbits were compared with values in rabbits conventionally raised with the doe. In GF rabbits given caecal flora, the values for most intestinal parameters were similar to values recorded in conventional animals. However colonization resistance to Escherichia coli was limited in GF rabbits given caecal flora diluted in doe's milk and severely impaired in GF rabbits given caecal flora without doe's milk, although relative caecal weight was normal. It is concluded that enteric microfloras should be preferably incorporated in doe's milk when dosed to GF rabbits to obtain acceptable gastrointestinal "normalization".

Animals

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.

Adult

Inhibition of secondary bile acid formation in the large intestine by lactulose in healthy subjects of two different age groups.

Secondary bile acids have been implicated in colonic carcinogenesis. Transformation of primary into secondary bile acids (7 alpha-dehydroxylation) in the large bowel is a pH-dependent process. Inhibition of this reaction could be achieved by lowering colonic pH. We, therefore, studied the effects of lactulose (a non-absorbable disaccharide), which is capable of acidifying colonic contents, on secondary bile acid metabolism. Because this metabolism is age dependent, lactulose was given (0.3 g kg-1 twice daily for 12 weeks) to nine middle-aged (age 31-54 years; mean 45.7) and ten elderly subjects (age 56-81 years; mean 66.4). Twice before, and after 6 and 12 weeks' lactulose administration, biliary and faecal bile acids, whole gut transit time, faecal weight and dry weight, and faecal pH were recorded. The concentration of (iso)lithocholic and deoxycholic acid in faeces was higher in elderly subjects (P less than 0.05) but the excretion was comparable. After lactulose the concentration and excretion of the major secondary bile acids decreased. The primary bile acid fraction rose from 5% before, to more than 20% after, lactulose (P less than 0.05). Faecal weight increased and faecal dry weight decreased, resulting in a higher faecal water output during lactulose. Whole gut transit time did not change. The faecal pH dropped after 6 (P less than 0.05) and further after 12 weeks' lactulose (P less than 0.05). The percentage deoxycholic acid in bile was higher, and cholic acid lower, in elderly subjects (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

'Normalization' of germfree mice after direct and indirect contact with mice having a 'normal' intestinal microflora.

Germfree mice were associated via direct and indirect contact with a 'normal' microflora by placing 'normal' mice in an isolator with germfree mice. Relative caecal weights, the ratio of secondary to primary bile acids, the presence of filamentous segmented bacteria in the small intestine and faecal beta-aspartylglycine were normal 5 days after direct contact and 15 days after indirect contact. Enterobacteriaceae were demonstrated by the third day after direct contact and the fourth day after indirect contact. Volatile and non-volatile fatty acids in the caecal contents were variable and appeared to be unrelated to the 'normalization' process of germfree mice after association with a microflora.

Animals

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.

Alanine Transaminase

An enzymic method for the determination of the glycine/taurine ratio of conjugated bile acids in bile.

A method is described in which the ratio of the glycine- to taurine-conjugated bile acids (G/T ratio) in bile is determined. After pretreatment of the bile for removal of the lipids, the bile acids are deconjugated enzymically with choloylglycine hydrolase (EC 3.5.1.24). The amino acids taurine and glycine are liberated in this way, after appropriate isolation, taurine and/or glycine are then determined with ninhydrin, enabling the establishment of the G/T ratio. A nearly complete hydrolysis was obtained for 6 conjugated bile acids, while the recovery of these acids when added to hog or ox bile was quantitative. The mean G/T ratio for hog bile, ox bile and human B-bile was 6.3, 2.5 and 2.0, respectively. The amount of total, free and conjugated bile acids can be determined by this method, combined with the 3alpha-hydroxysteroid dehydrogenase technique for bile acid determination described by Iwata and Yamasaki [1]. A high G/T ratio was observed in 3 cases of Crohn's disease in the small bowel, but the extent of deconjugation in B-bile was lower than in duodenal fluid. The determination of the G/T ratio can be complementary to our knowledge of the metabolism of bile salts in certain gastro-intestinal disorders.

Amidohydrolases