Transport mechanism of L-[14C]glutamate in cortical slices and synaptosomes of rabbits exposed to brain ischemia and reperfusion

Molecular and chemical neuropathology - Changes in the functioning of the glutamatergic system in rabbit brain were studied after partial brain ischemia and reperfusion. In vitro studies were...     

Structural and functional integrity of precision-cut liver slices in xenobiotic metabolism: a comparison of the dynamic organ and multiwell plate culture procedures

1. Objectives were two-fold: (1) to compare the viability of precision-cut liver slices in two culture systems, namely the dynamic organ and the multiwell plate; and (2) to evaluate whether increasing the number of slices per incubation results in a proportional increase in the extent of metabolism. 2. With both culturing systems, the major products of 7-ethoxycoumarin metabolism were the sulphate and glucuronide conjugates of 7-hydroxycoumarin with very low levels of the free compound. When the multiwell plate procedure was used, metabolism increased linearly for at least 10 h, whereas it tended to plateau after 6 h in the dynamic organ culture system. At preincubations > 10 h, significantly more metabolism of 7-ethoxycoumarin was seen in the slices cultured using the multiwell system compared with the dynamic organ system. 3. Morphological evaluation employing light and electron microscopy revealed that liver slices incubated using the multiwell system were structurally better preserved compared with those incubated using the dynamic organ system. 4. Using the multiwell system, increasing the number of slices per incubation from one to two resulted in only a modest increase in the metabolism of 7-ethoxycoumarin. The rate of metabolism of this substrate was much higher with one liver slice when expressed per mg homogenate protein. 5. It is concluded that (1) the multiwell plate culture system for culturing slices is superior to the dynamic organ system in studying the metabolism of xenobiotics following long-term incubations, (2) increasing the number of slices per incubation does not result in a corresponding increase in the rate of metabolism, and (3) in both culture systems optimal viability appears to be within 24 h of incubation.     

Lung cancer in relation to occupational and environmental chromium exposure and smoking

The increased occurrence of lung cancer in residents of Dolny Kubin, the North-Slovakia district with ferrochromium industry, compared to the general population of Slovakia, led us to the study assessing influence of the occupational and environmantal exposure to chromium on the lung cancer incidence, respecting also the risk coming from cigarette smoking. Residents of Dolny Kubin district with the diagnosed lung cancer in 1984-1999 were involved in the study. The occurrence of lung cancer was significantly higher in people working in ferrochromium industry. The age at the onset of the disease in people exposed to chromium was by 5.5 years lower than in non-exposed. Smoking was an important risk factor, which has been proved particularly in non-exposed group where 62% were smokers and the onset of the lung cancer in them occured about 3.4 years earlier than in non-smokers. In exposed groups, no significant effect of smoking was found. We can conclude, that occupational exposure to chromium was identified as the main risk factor of lung cancer in Dolny Kubin district even overlaying effect of smoking.     

Characteristics of oxidative stress in experimental rat brain ischemia aggravated by homocysteic acid

We developed a new experimental model of oxidative stress in rats, which combines the effects of 3-vessel brain ischemia and an increased level of homocysteine in blood circulation. We compared the protective effects of two compounds, the agonist of cannabinoid receptors Win5521-2 and the natural antioxidant carnosine. We found that Win5521-2 has a protective effect only at a normal blood level of homocysteine, whereas carnosine is also effective under conditions of elevated homocysteine level.     

Proliferation of hepatic peroxisomes in rats following the intake of green or black tea.

Rats maintained on green, black or decaffeinated black tea (2.5%, w/v) as their sole drinking fluid displayed higher hepatic CN- insensitive palmitoyl CoA oxidase activity than controls; the extent of increase was similar with the three types of tea. Morphological examination of the liver using electron microscopy revealed an increase in the number of peroxisomes in the tea-treated animals. The same treatment of the animals with green and black tea resulted in a similar rise in hepatic microsomal lauric acid hydroxylation. Analysis by HPLC of the aqueous tea extracts employed in the current study showed that the total flavanol content of the green variety was much higher than the black varieties, and confirmed the absence of caffeine in the decaffeinated black tea. It may be concluded from the present studies that neither caffeine nor flavanoids are likely to be responsible for the proliferation of peroxisomes observed in rats treated with tea.     

Lysosomes of the renal cortex: heterogeneity and role in protein handling

Rate sedimentation of the kidney cortical mitochondrial/lysosomal (ML) fraction yields two distinct classes of lysosomes: the large lysosomes or protein droplets and a heterogeneous broad band of smaller lysosomes. The protein droplets which are recovered as a well defined zone of high purity also sediment as a homogeneous band after equilibrium banding at a density of 1.235 g/ml in sucrose. The small lysosomes co-sediment with other subcellular organelles as a broad band, indicated by the distribution of various acid hydrolases, which exhibit subtle heterogeneity among these small lysosomes. The distribution of renin containing granules indicates that in size they represent a distinct subpopulation of small lysosomes. Further fractionation of small lysosomes by equilibrium banding separates two distinct populations at densities 1.20 (small light) and 1.235 g/ml (small dense). Comparison of lysosomal populations fractionated in these studies with the distribution of lysosomal acid hydrolases along the different segments of the nephron suggests that large and small dense lysosomes probably originate from the proximal tubule while the small light lysosomes may contain lysosomes from the distal tubule. Very small, lysosome-like organelles subfractionated from the 'microsomes' may constitute a mixture of small light lysosomes, lysosomal fragments and endocytic vesicles from a variety of cell types. Time course studies with 3H labelled Cd-thionein, following intravenous administration, suggests that uptake in the kidney cortex is very rapid and that catabolism takes place in two distinct phases: rapid breakdown starting in the endosome compartment and slower breakdown in lysosomes. From the association of labelled lysozyme (125I) and Cd-thionein (109Cd) it appears that all the different lysosomal populations identified are at some stage involved with uptake and catabolism of these two proteins.     

Association between estrogen receptor β polymorphisms and prostate cancer in a Slovak population

Sex steroid hormones have important roles in the function of the prostate; however, they may also serve as factors in the initiation and progression of carcinogenesis. Estrogens, acting through estrogen receptors, may significantly affect prostate cancer development and progression. The main aim of the present study was to analyze the association between the rs3020449, rs4986938 and rs1256049 polymorphisms in the promoter region of the estrogen receptor β (ESR2) gene and prostate cancer risk in the Slovak population. A total of 510 patients with prostate cancer and 184 healthy men were included in the present study. No association between the rs4986938 and rs1256049 polymorphisms and prostate cancer development and progression was revealed; however, there was a statistically significant association between the rs3020449 GG genotype [odds ratio (OR), 2.35; P=0.002] and the G allele (OR, 1.42; P=0.005) and a higher risk of prostate cancer development. The rs3020449 GG genotype was significantly associated with a higher risk of development of carcinoma with a Gleason score >7 (OR, 2.66; P=0.005), as well as with the development of carcinoma with pT3/pT4 (OR, 2.28; P=0.02). According to the results from the present study, the rs3020449 polymorphism, in the promoter region of ESR2, may be considered to have a role in the development and progression of prostate cancer in the Slovak population.     

Effect of fasting on lysosomes in kidney cortex of glomerulonephritic rats

The effect of food restriction (FR) on the kidney cortex lysosomes prepared by rate and isopycnic zonal centrifugation was studied in rats with passive Heymann glomerulonephritis (PHN). FR reduced the renal mass by 41%, but the capacity for handling of labelled endocytosed proteins by the lysosomes was not different from fed PHN rats. While PHN with heavy proteinuria increased the recovery of lysosomal enzymes in the large lysosomes located in the proximal tubule, no changes were observed in FR-PHN rats in spite of significant proteinuria. The density of the small lysosomes was significantly shifted/reduced (from 1,200 and 1,235 g/ml to 1,185 and 1,225 g/ml, respectively) in both fed and FR-PHN rats, suggesting that the handling of extra loads of protein may enhance the absorptive function of small lysosomes found in the lower part of the nephron. FR reduced the mechanical fragility of lysosomes in the kidney cortex of PHN-rats. The highly increased urinary excretion of lysosomal enzymes in fed PHN rats was not observed in FR-PHN rats. As a conclusion, FR reduces both the fragility of lysosomes and the proportion of digestive enzymes in fragile lysosomes. These lysosomal enzymes may be of pathogenic importance in PHN causing cell damage when liberated from disrupted lysosomes.     

Zur Pathogenese des lympho-plasmacellulären Rundinfiltrates der Lunge

We investigated four cases of pulmonary plasmocytoma. We tried to demonstrate that their morphogenesis indicates maturation of nonspecific granulation tissue. We suppose these formations to be tumor-like granulomas which a rise preferentially in the younger age groups in association with chronic nonspecific pneumonia. Their etiology is unknown. They are not true neoplasms, as asserted by many authors.