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Biomedical subjects

R Preisig

Publications and source records attributed to R Preisig.

At least 55 records · Page 3Linked to original sources
PubMed1981

Assessment of the cytochrome P-448 dependent liver enzyme system by a caffeine breath test.

[1-Methyl-14C], [3-Methyl-14C] and [7-Methyl-14C] caffeine were used to investigate demethylation in control rats, and in rats pretreated with phenobarbital or 3-methylcholanthrene, by a 14CO2-exhalation test. Compared to controls, pretreatment with phenobarbital did not enhance demethylation of any of the labelled caffeines. In contrast, induction by 3-methylcholanthrene, presumably of cytochrome P-448, resulted in highly significant increases in peak 14CO2 exhalation rates, 14CO2 disappearance constants and areas under the exhalation rate - time curves. Based on these results, [7-methyl-14C] and [3-methyl-14C] caffeine were chosen for assessing the feasibility of a caffeine breath test in man, using 5 normal volunteers and 2 patients with compensated liver cirrhosis. 14CO2 exhalation curves in cirrhotics were clearly different from those in normal volunteers, being characterised by a slower rise and a lower specific activity of exhaled 14CO2. Since the variability of the levels of the specific activity in subjects with normal livers suggested the influence of extraneous factors, a second group of normal volunteers, smokers and nonsmokers, was investigated. With either labels, the average 14CO2 exhalation rate was doubled in smokers. From these studies in rats and preliminary results in man it is concluded that specifically labelled caffeine is a suitable and promising substrate for studying demethylation by breath analysis. Presumably, caffeine represents a safe and sensitive indicator of the activity of the cytochrome P-448 system.

Adult↗
PubMed1981

Nicotinic acid test in the diagnosis of Gilbert's syndrome: correlation with bilirubin clearance.

A provocation test with nicotinic acid (50 mg intravenously) was performed in 13 patients with Gilbert's syndrome and seven healthy volunteers to investigate the diagnostic value of several test parameters and to correlate them with the bilirubin clearance. The maximal increment of unconjugated serum bilirubin, the retention at four hours, and the area under the bilirubin concentration time curve. (AUC) were measured. Significant differences between patients and controls were found with regard to the AUC (7.95 +/- SD, 3.29 mmol/min/l vs. 3.08 +/- 0.57; P less than 0.001), the increment of unconjugated bilirubin (24.1 +/- 7.1 mumol/l vs. 10.2 +/- 3.2; P less than 0.001) and the retention (77.7 +/- 8.9% vs. 45.8 +/- 27.4%; P less than 0.02). Of those, the AUC discriminated best between patients and controls. Five patients with Gilbert's syndrome had normal serum bilirubin concentrations (less than 17.1 mumol/l = 1 mg%) at the time of the study, but abnormal AUC and bilirubin increment. A significant correlation was found between the bilirubin clearance and the retention (r = -0.96; P less than 0.001) as well as the AUC (r = -0.82; P less than 0.05) but not with the bilirubin increment. This simple test may be used to assess the disturbance of bilirubin clearance in Gilbert's syndrome.

Adult↗
PubMed1981

Choleresis and bile pigment excretion in the nutria.

Mean excretory rates of endogenous biliverdin (BV) and bilirubin (BR) in nutria were determined to be 6.0 +/- 1.0 and 0.67 +/- 0.10 microgram/min/kg, respectively. Endogenous bile flow was 33 +/- 7.0 microliter/min/kg. Infusion of sodium taurocholate at rates above 0.1 mumol/min/kg resulted in cholestasis. Hepatic transport maxima for BR conjugates following the infusion of unconjugated BR were 120 and 130 micrograms/min/kg. Although nutria excrete predominantly BV like avian and reptilian species, they differ by readily excreting an exogenous load of unconjugated BR.

Animals↗
PubMed1980

Increased systemic availability of drugs during acute ethanol intoxication: studies with mephenytoin in the dog.

The influence of ethanol on the fate of orally administered drugs which normally undergo a high presystemic elimination is as yet ill-defined. Experiments, therefore, were designed in four nonanesthetized dogs with mephenytoin as model compound. The drug was administered p.o. or i.v., and throughout an 8-hr period ethanol (100 mg kg-1 hr-1) or saline was infused according to a cross-over design. Concentrations of mephenytoin and its main metabolites, nirvanol and p-hydroxymephenytoin, were determined by gas-liquid chromatography. In experiments with oral mephenytoin administration and ethanol infusion, mephenytoin peak plasma concentrations were elevated by 87.0 +/- 15.2% (S.E.M.) (P less than .005, n = 4). Correspondingly, the average area under the plasma concentration time curve was increased to 229% of control (P less than .005). Ethanol also reduced metabolite formation; the area under the plasma concentration time curve for nirvanol was reduced by 40% (P less than .005). Urinary output of nirvanol was diminished to 51% and of p-hydroxymephenytoin to 73% (P less than .05, n = 12). It is concluded that drug ethanol interactions may be particularly prominent for orally administered drugs which normally are subject to a high presystemic elimination. This mechanism might be a clinically relevant cause for ethanol related drug toxicity.

Administration, Oral↗
PubMed1980

[The effect of clanobutin on bile excretion in rat and dog (author's transl)].

The effect of 4-[p-chloro-N-(p-methoxyphenyl)-benzamido] butyric acid (clanobutin, Bykahepar) on bile formation was studied in anesthetized male Sprague-Dawley rats and in non-anesthetized female boxer dogs. Following i.v. injection of 40 mg/kg body weight of clanobutin, a marked choleresis paralleling the biliary excretion of the drug was observed in both species. The biliary elimination of 1 mumol clanobutin (and metabolites) caused on the average an increment of bile flow of 90 microliter and 11.5 microliter in the rat and dog, respectively. Bile flow was linearly related to clanobutin excretion in rat and dog. Within the period of observation 55% of the dose of clanobutin in the rat, and 80% of the dose in the dog were eliminated via the bile; urinary excretion amounted to 3% of the dose. In rat bile, 32% of the clanobutin was present as the parent compound; the remaining 68% consisted of 3 metabolites. Measurement of the erythritol clearance in the dog suggests that clanobutin stimulates the bile salt-independent, canalicular bile formation. In addition, however, the observed changes in the bile/plasma concentration ratio of erythritol, as well as a predominant excretion of bicarbonate and chloride point to a possible ductular effect of clanobutin. In these acute studies, the drug did not influence the bile salt, phospholipid or cholesterol excretion. Cholesterol saturation of bile was unaffected.

Animals↗
PubMed1980

[The galactose breath test. Modification of the method and comparison with galactose elimination capacity and plasma disappearance of bromsulphatein (author's transl)].

The paper describes a modification of the galactose breath test (GBT) for assessing liver function. Following iv injection of 0.5 g galactose per kg body weight, together with 2 mu Ci generally 14C-labelled galactose, 14CO2 is collected in regular intervals during one hour. Since 14C-activity in breath exhibits a linear rise during 70--100 minutes, the curve obtained permits calculation of an initial slope, as well as the "standardized specific activity" after 45 min GBT was performed in 8 liver normals, 8 alcoholic cirrhotics, 4 patients with chronic active hepatitis (CAH) and 6 with primary biliary cirrhosis (PBC). The results were compared with the simultaneously measured galactose elimination capacity (GEC) and the initial plasma disappearance (ki) of bromsulphthalein (BSP). In the liver normals, the values for initial slope and standardized specific activity were 1.08 +/- S.D. 0.3 and 0.42 +/- S.D. 0.1, respectively. In comparison, the values obtained in all patients groups were markedly reduced. CAH patients exhibited the most severe decrease; the reduction was smallest in PBC patients. The GBT discriminated well between liver normals and patients with liver disease (p less than 0.001, t-test). The results of the GBT correlated linearly with GEC (r = 0.86 and 0.87, respectively) and with BSP-ki (r = 0.9 and 0.92, respectively). These results suggest that the GBT may be regarded as a quantitative measure of a cystosolic hepatic function.

Aged↗
PubMed1980

[Hydrops of the gallbladder].

Of 739 cholecystectomies carried out from 1971 to 1978, 40 cases revealed intraoperatively a hydrops of the gallbladder. This hydrops was caused in all cases by a stone located in the gallbladder neck or the cystic duct. In 37 cases, the gallbladder contents were examined: clear "white bile" was present in 29 (78%); this was always very viscous. With one exception, all biles were found to be sterile. The pressure in the gallbladder averaged 61.5 cm saline, ranging from 15 to 115 cm. The osmolality of bile was on the average 295 mosmol/kg, thus being roughly isotonic with blood. In three cases, where chemical analysis of the bile was perfomed, bilirubin-, bile salts, cholesterol-, phospholipids, and protein-content were reduced to non-measurable amounts or to concentrations below 1 mg%. It is suggested that the mucosal inflammation following the obstruction to bile flow leads to disturbances in reabsorptive processes, secretion of mucous and a subsequent increase in intraluminal pressure.

Adult↗
PubMed1979

[Bile acid concentration in serum after a test meal in hepatobiliary diseases. A comparison with quantitative liver function tests].

The concentration of bile acids in serum was measured by an enzymatic-fluorometric method under fasting conditions and 2 hours after a standardized meal in 26 patients with chronic liver disease (chronic hepatitis, liver cirrhosis, primary biliary cirrhosis) and compared with other tests of liver function. Postprandial bile acids and transaminases were false negative in only 12% and are thus the most sensitive tests after the BSP-retention test (3% false negative results). In comparison, fasting bile acids proved to be a relatively insensitive screening test for liver disease (38% false negative results). Postprandial bile acids were more closely correlated with BSP retention and BSP disappearance rate constant (Ki) than fasting bile acids. In view of these findings postprandial serum bile acid concentrations should be preferred to fasting bile acid concentrations in screening for liver disease and monitoring liver function.

Adult↗
PubMed1979

Hepatitis, cardiomyopathy and hemodynamics in furazolidone-induced round heart disease of turkeys.

Twenty-five large broad-breasted white turkeys were fed a 22% protein diet supplemented with 500 ppm furazolidone from day 1 to 3.5 weeks of age and the same diet supplemented with 700 ppm furazolidone until 9.5 weeks of age. Following the development of round heart disease as indicated by altered electrocardiograms the 25 turkeys were sacrificed. In the livers of turkeys with biventricular dilatation (72% of cases) there was bile duct hyperlasia, portal fibrosis and intracytoplasmic globules in the hepatocytes. Globules stained pink with hematoxylin-eosin, deep red with PAS and variable with Massons trichrome stains in paraffin-embedded liver sections. Clear intracytoplasmic vacuoles demonstrable in hepatocytes of PAS stained liver sections embedded in paraffin did not stain as lipid in frozen sections but did contain sparse flocculent material in 1 micrometer sections of liver embedded in epoxy resin and stained with toluidine blue. At the subcellular level, the intracytoplasmic globules in hepatocytes were surrounded by a single membrane, contained flocculent material and had enzymatic properties characteristic of lysosomes. Blood pressure, heart rate, dp/dt max, total plasma proteins and plasma trypsin inhibitory capacity of turkeys with round heart disease were lower than corresponding values for control turkeys. Control turkeys did not exhibit the characteristic gross or microscopic lesions of round heart disease.

Animals↗
PubMed1979

[Hepatic extraction of taurocholate and indocyanine green in patients with liver disease (author's transl)].

Bile acids are increasingly used as test substances for the estimation of liver function and it has been postulated that radioactive labeled bile acids have advantages over indocyanine green (ICG) for measurement of hepatic blood flow. Therefore, the hepatic extractions of 14C-taurocholate and ICG were compared in 23 patients with liver disease and correlated with various parameters of hepatic function. The hepatic extractions of 14C-taurocholate (mean: 42 +/- SD 17%) and ICG (mean: 35 +/- SD 18%) were similar. The correlations with galactose elimination capacity and BSP plasma disappearance were closer for ICG than for 14C-taurocholate extraction. Hepatic blood flow measured with 14C-taurocholate (mean: 1.45 +/- SD 0.51 l/min) correlated well (r = 0.81) with the respective values obtained with ICG (mean: 1.17 +/- SD 0.49 l/min), but was about 22% larger. This study does not provide evidence that 14C-taurocholate is superior to ICG as an intravenous test substance for measurement of hepatic function or blood flow.

Adult↗
PubMed1978

Polymorphic acetylation and aminopyrine demethylation in Gilbert's syndrome.

Polymorphic acetylation was investigated in twenty-seven patients with Gilbert's syndrome using the sulphadimidine test. Whereas the finding of 51% slow acetylators in seventy-eight control persons agreed well with the expected frequency in a continental European population, the prevalence of slow acetylators in Gilbert's syndrome was increased to 78% (P less than 0.03, Woolf's G-test). After oral administration of 14C-aminopyrine there was no significant difference between seventeen patients with Gilbert's syndrome and twenty-seven normal controls in total plasma clearance of aminopyrine (280 +/- SD 100 and 270 +/- 60 ml/min) and in the disappearance curve of 14CO2 in breath (0.23 +/- 0.04 and 0.22 +/- 0.03 h-1, respectively). Thus, whereas aminopyrine metabolism appears unaffected in the examined patients, the data documents a new association between slow acetylator status and Gilbert's syndrome.

Acetylation↗
PubMed1977

[The aminopyrine respiratory test under the acute effect of ethanol. Evaluation of a new method for the measurement of microsomal functions of the liver].

Microsomal demethylation, a partial function of the liver, can be estimated by the aminopyrine breath test. Both the determination of specific activity and the disappearance rate constant for 14CO2 in breath demand the assumption of rapid formaldehyde oxidation to CO2. Conversely, the disappearance of aminopyrine from plasma reflects microsomal aminopyrine metabolism only. Ethanol is known to affect both microsomal demethylation and formaldehyde metabolism. If in the presence of ethanol the latter process should become rate-limiting, a discrepancy between the data obtained in breath and in plasma could be expected. In order to investigate this possibility 10 fasting healthy male volunteers received 9 mg/kg (dimethylamine-14C)-aminopyrine (2 muCi) orally and, 3 hs later, 0.7 g/kg ethanol. Immediately following ethanol the specific activity of 14CO2 in breath decreased by 25% (p less than 0.005) and the disappearance of 14CO2 from breath was 31% lower than in 17 matched controls (p less than 0.005). The aminopyrine plasma disappearance rate, determined by GLC, decreased by 30% after ethanol (p less than 0.05). Since the decrease in aminopyrine plasma disappearance rate seems to account for the proportional decreases obtained by breath analysis, it is concluded that the aminopyrine breath test expresses the rate of microsomal demethylation even during altered formaldehyde metabolism, e.g. in acute ethanol intoxication.

Aminopyrine↗
PubMed1977

Stereoselective metabolism, pharmacokinetics and biliary elimination of phenylethylhydantoin (Nirvanol) in the dog.

The influence of stereoisomerism on pharmacokinetics and rates of hepatic drug metabolism was investigated in four dogs using the enantiomers of phenylethylhydantoin (PEH) as model substances. After single i.v. administration of 98 micromoles of the pure enantiomers per kg b.wt., concentrations were measured by gas-liquid chromatography. The l-form exhibited a longer plasma half-life (23.3 +/- S.E. 1.0 hour) than the d-form (16.3 +/- 1.0 hour, P less than .005). Volumes of distribution and renal clearances were practically identical. The differences in plasma half-lives of PEH were explained by stereoselectivity of hepatic hydroxylation: an approximately 10-fold differences was found in urinary excretion of their major metabolities, d- and l-hydroxyphenylethylhydantoin (HPEH). Furthermore, in bile 7.3 +/- 1.6 mumol of of d-HPEH were eliminated within the first 6 hours, whereas l-HPEH could not be detected. The preference in biliary output of d- compared with l-PEH is consistent with the idea that both hepatic uptake and microsomal hydroxylation of PEH contribute to the high degree of stereoselectivity. In view of similar extrahepatic, but different metabolic behavior of these enantiomers, they represent an interesting research tool for in vivo studies of drug metabolism: in otherwise identical conditions, two different rates of PEH hydroxylation may be studied.

Animals↗