[Comparative pathology of early stress-induced changes in the duodenal mucosa in laboratory rats and in humans]. / Srovnávací patologie casných stresových zmen duodenální sliznice u laboratorních potkanu a u cloveka.

BACKGROUND: Our presentation comprises results of two studies: The first was an experimental investigation of 60 Wistar-strain rats used in a toxicological study. The other part analysed stress changes in the duodenal mucosa in the human autopsy material. Both humans and rats had been exposed to stress and showed similar histological changes. METHODS AND RESULTS: In the rats the same duodenal lesions were present both in the test group and the control animals in the toxicological study. Lesions consisted of oedema of the duodenal villi and erosions in the tips of the villi. We believe that in the experimental group the stress was caused by restraining the animals by daily introduction of the gastric metallic tube, by taking blood from the retrobulbar plexus, and by anaesthesia. CONCLUSIONS: The autopsy study comprised 35 cases displaying congestion and macroscopically recognizable multifocal bleeding into the duodenal mucosal folds. The microscopic investigation revealed bleeding into the mucosal villi and small erosions. In some cases there were cuneiform mucosal infarcts extending into the submucosa. In the humans, severe cardiovascular diseases and circulatory disturbances represented the main causes of the stress. Local hypoxia and gastric juice acidity were involved in the pathogenesis of the duodenal mucosal changes.

In vitro glycosidation potential towards olomoucine-type cyclin-dependent kinase inhibitors in rodent and primate microsomes.

Interspecies differences in glycosidation potential in mammalian tissues represent a factor contributing to ambiguity when endobiotic and/or xenobiotic metabolic pathways are extrapolated from animals to man. Using the TLC/autoradiographic technique, we conducted an in vitro investigation involving mouse, rat, monkey, as well as human liver and kidney microsomes to evaluate their glycoconjugation potential towards (3)H-labeled, purine-derived selective inhibitors of cyclin-dependent kinases such as olomoucine, bohemine, roscovitine, 6-(2-hydroxybenzyl)amino-2-(1-hydroxymethyl-2-methylpropyl)amino-9-isopropylpurine (compound A-4), and 6-(3-hydroxybenzyl)amino-2-[(1(R/S)-hydroxymethyl)propyl]amino-9-isopropylpurine (compound A-5) as aglycones. Principally, this study confirmed the aliphatic hydroxyl group of olomoucine-type inhibitors as a relatively suitable target for glucuronide, glucoside, xyloside, galactoside, and/or N-acetylaminoglucoside conjugation. Of the tissues examined, only the mouse microsomes were able to perform glucosidation and galactosidation reactions with the aglycones. On the other hand, monkey microsomes were superior to the mouse microsomes in a variety of glucuronide conjugates produced with compounds A-4 and A-5.

Lymphocytic thyroiditis in beagle dogs in a breeding colony: histological findings.

During the 18-year (1974-1991) period the lymphocytic thyroiditis was found in 8% of 2238 animals from a Beagle dog breeding colony (8.5% of 1079 males and 7.6% of 1159 females). The thyroid glands of affected animals were on average heavier by 10.4% in males and by 21.0% in females. In the histological picture the interstitial lymphocytic infiltrations of various ranges accompanied by varying degree of follicular damage prevailed. The earliest findings of this lesion were revealed in 9-month old animals.

[Disposition of [3H]flobufen and its active metabolite in rats]. / Dispozice [3H]flobufenu a jeho aktivního metabolitu u krys.

The present authors investigated the excretion, distribution and pharmacokinetics of the novel potential antirheumatic agent flobufen and its active metabolite after p.o. and i.v. doses of 2, 10 and 50 mg/kg administered to rats. The drug is resorbed well from the digestive tract and mostly it is metabolized to the principal metabolite M, which is only slowly excreted from the organism mainly by renal clearance. Within the whole dose range the kinetics of the drug is linear. Binding of flobufen and M to proteins is high (95-99%). The highest concentrations of radioactive metabolites (mostly M) were found in the plasma, liver, lungs, kidneys, connective tissue and inflammatory foci. The penetration of metabolites through the placenta and excretion in human milk are relatively important.

Plasma concentration, tissue distribution and excretion of the prospective cardioprotective agent cis-(-)-2,3,4,4a,5,9b-hexahydro-2,8-dimethyl-1H-pyrido-[4,3-b]indole dihydrochloride in rats.

Pharmacokinetics of cis-(-)-2,3,4,4a,5,9b-hexahydro-2,8-dimethyl- 1H-pyrido-[4,3-b]indole dihydrochloride (Stobadin; in the following briefly called STB), a pharmacologically active stereoisomer of the gamma-carboline carbidine, was studied using a 3H-labelled product. Determination of STB in biological material was based on liquid-liquid extraction from alkaline media into n-heptane. The plasma concentration of STB following i.v. administration to rats was approximated by a biexponential function. An open two-compartment pharmacokinetic model was conferred to the data with the following parameter estimates: terminal elimination half-life 85.6 min, distribution volume at steady state 4.78 l/kg, total body clearance 105.3 ml/min/kg. The systemic availability of orally given STB dihydrochloride in solution was 19.7%. The brain uptake index of STB was 78.2%. Autoradiography in rats injected i.v. showed a heterogenous distribution of the label in the tissues. STB showed strong affinity to the lung tissue and kidneys and was evenly distributed in the cortex and medulla of the latter organ. During 72 h after i.v. administration, 64.6% and 11.0% of the 3H dose was excreted into urine and faeces, respectively, and after oral administration, the excretion was 62.0% and 21.9%, respectively.

[Disposition of the potential antidepressive agent (3H) VUFB 15468 in mice and rats]. / Dispozice potenciálního antidepresíva (3H) VUFB 15468 u mysí a krys.

Excretion, biodistribution and pharmacokinetics of the above-mentioned drug after oral doses of 10 and 50 mg/kg were investigated. The drug is completely and rapidly resorbed from the digestive tract. It shows relatively large renal and metabolic clearance, it is extensively distributed in the tissues This results in its rapid elimination from plasma (t1/2 approximately 3 h) and, on the other hand, higher concentrations of radioactive drugs in tissues. Penetration and specific binding of VUFB 15468 in the murine brain in dependence on the administered dose were tested (ED50 approximately 4 mg/kg). Autoradiographic examination of the rat brain demonstrated an increased concentration of radioactive drugs in the cerebral cortex, hippocampus, hypophysis and central ganglia.

[Preparation technic and possibilities of use of histological whole-body sections of small laboratory animals]. / Technika prípravy a moznosti vyuzití histologických rezu pres malá laboratorní zvírata.

A preparation technique for whole-body sections of small laboratory animals (mouse, rat) is introduced comprising, cutting, drying and fixation of sections, staining and mounting. Sections can be used for whole body autoradiography as well as for histochemical, immunohistochemical, anatomical, pathological and distributional analytical evaluations.