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Biomedical subjects

J Kanta

Publications and source records attributed to J Kanta.

At least 19 recordsLinked to original sources

Selective inhibition of hepatic collagen accumulation in experimental liver fibrosis in rats by a new prolyl 4-hydroxylase inhibitor.

Fibrosis and cirrhosis of the liver are often the result of chronic liver damage by a variety of different agents. Pathological accumulation of collagen, disruption of the lobular structure, and impaired hepatocellular function frequently lead to systemic involvement and fatal complications. Drugs inhibiting collagen hydroxylation and accumulation are expected to improve this situation, making prolyl 4-hydroxylase (P4H), the key enzyme of intracellular collagen processing, a rational target for pharmacological intervention. S 4682, a novel inhibitor of purified P4H (Ki = 155 nmol/L), reduced hydroxyproline (Hyp) synthesis in chicken embryo calvaria (IC50 = 8.2 micromol/L) and in cultured hepatic stellate cells (HSC) (IC50 = 39 micromol/L). S 4682 inhibited hepatic collagen hydroxylation in vivo after metabolic labeling with [14C]proline. In the CCl4 model of chronic hepatic injury, characterized by histologically and biochemically evident fibrosis and highly elevated levels of serum procollagen type III N-peptide, S 4682 reduced hepatic collagen accumulation, decreased prevalence of ascites, and lowered serum procollagen type III N-peptide (PIIINP) levels. The hepatic Hyp content of drug-treated animals was closely correlated with serum levels of PIIINP S 4682 had no influence on Hyp content of heart, lung, and kidney.

Animals↗

Hepatocyte proliferation in silicotic rat liver after partial hepatectomy.

Liver silicosis was induced in rats by an intravenous injection of silica particles. The presence of silicotic granulomas in the liver lowered the initial response of hepatocytes to partial (37%) hepatectomy and slowed down the decline in the number of dividing cells 6 days after the stimulus, but did not affect significantly the total number of mitotic cells.

Animals↗

Ultrastructure of rabbit tracheal epithelium after the administration of Hexabrix--a hexaiodated contrast agent for tracheobronchography.

The ultrastructure of the tracheal epithelium after the application of 1 ml of Hexabrix (a hexaiodated contrast agent for tracheobronchography) into the airways was studied. Severely altered pseudostratified columnar epithelium was found in the trachea. Eighty-one +/- 5% of the goblet cells had been stimulated to discharged mucus. Forty-three +/- 3% of them were completely exhausted and had degenerated. The ciliated cells displayed marked signs of pathological alteration up to vacuolar degeneration. The ciliary border above the epithelium was severely damaged. The mean number of cilia per micron 2 fell to 3.3 +/- 0.5, but the proportion of intact cilia did not drop below 95%. As morphological signs of impaired self-cleaning ability of the airway epithelium, a large amount of inspissated mucus and numerous bacteria were found in the area of the impaired ciliary border. Coarse grained contrast substance of supreme electron density was intermingled with the condensed mucus. The most pronounced damage to the cells was observed at the sites of direct contact of the contrast agent with the cell membranes.

Animals↗

Prolonged reduction of hepatocyte proliferative ability in rats after a single treatment with carbon tetrachloride.

Female Wistar rats were pretreated with I ml of carbon tetrachloride/kg of body weight or with olive oil. All the rats were given this dose of CCl4 20 or 40 days later. Liver regeneration as evaluated by 3H-thymidine incorporation into liver DNA and by the number of mitotic hepatocytes was markedly impaired in CCl4-pretreated rats when compared with olive oil-pretreated controls. DNA labelling reached only 83 and 59% and mitotic index 35 and 58% of control values, respectively, at 20-day and 40-day time intervals. The variables characteristic of liver damage did not parallel the changes in cell division. About 20% of hepatocytes were necrotic both in the CCl4-pretreated and in the control rats. The activity of serum alanine aminotransferase was higher in the CCl4-pretreated rats. Only serum aspartate aminotransferase activities were somewhat lower when compared to controls. Similarly, serum aminotransferases were much less affected by the pretreatment than the markers of regeneration when two low doses of CCl4 (0.125 ml/kg) were given to rats 20 days apart. The activities of microsomal enzymes aniline hydroxylase and pethidine demethylase were equal in control and in experimental rats 20 days after CCl4 pretreatment which indicated that the effects of CCl4 were not mediated by an overall decrease in cytochrome P-450 enzymes. In summary, a single pretreatment of rats with CCl4 induced changes in liver that lasted for 40 days and impaired liver regeneration when another dose of CCl4 was applied.

Alanine Transaminase↗

[Epiglottitis and subglottic laryngitis].

Account of the course and conclusions of a working session of the Paediatric Society devoted to laryngeal obstruction in children. The participants discussed in particular the differential diagnosis of subglottic laryngitis and epiglottitis in children.

Child↗

Relationship of liver damage and liver regeneration after carbon tetrachloride treatment in rats.

Various doses of carbon tetrachloride (0.625 mmol to 10 mmol CCl4/kg body weight) were administered to female Wistar rats. Liver damage after a single treatment was evaluated by serum aminotransferase levels and by the extent of necrotic areas in parenchyma. Liver regeneration was evaluated by 3H-thymidine incorporation into liver DNA and by the number of dividing hepatocytes. Mitotic index of hepatocytes rose in parallel with the specific activity of DNA and with the extent of necrosis. However, the activities of serum aminotransferase AST and ALT increased much more rapidly and did not correlate either with necrosis or with regeneration rate. Increased membrane permeability in morphologically intact cells, increased synthesis of the enzymes by the liver as well as the leakage from necrotic cells are discussed as possible causes of the high aminotransferase activities in serum.

Alanine Transaminase↗

Regenerative ability of hepatocytes is inhibited in early stages of liver fibrosis.

Female Wistar rats were given three doses of carbon tetrachloride, 10.4 mmol/kg of body weight. The doses were administered within 16 days and another 16 days were allowed to pass before partial (37%) hepatectomy was done. The liver showed very mild fibrosis at that time. DNA synthesis (measured by 3H-thymidine incorporation) was decreased by 53% and mitotic activity of hepatocytes was decreased by 56% when compared to olive oil-pretreated partially hepatectomized controls. The results show that the mitotic potential of hepatocytes in early stages of liver fibrosis is impaired which may influence the course of the disease.

Animals↗

The effect of Hexabrix tracheobronchography on the ultrastructure of the airway epithelium.

The ultrastructure of the airway epithelium was studied after experimental Hexabrix tracheobronchography. Serious damage to the tracheal epithelium due to Hexabrix was recorded. 81 +/- 5% of goblet cells were stimulated to discharge mucus. 43 +/- 3% were completely exhausted and degenerated. The ciliated cells displayed vacuolar degeneration or severe pathological alteration. The average number of cilia/micron 2 fell to 3.3 +/- 0.5. As morphological signs of impaired self-cleaning ability the inspissated mucus and numerous bacteria appeared in the area of the disorganized ciliary border.

Animals↗

Effect of bronchoalveolar lavage on the ultrastructure of the tracheal epithelium in rabbits.

Serious damage to the tracheal epithelium due to bronchoalveolar lavage (BAL) was recorded. Immediately after BAL 99 +/- 2% of goblet cells were exhausted and degenerated. Their regeneration began 24 h after BAL resulting in hyperplasia of goblet cells with the formation of endoepithelial mucous glands. The most pronounced injury to the ciliated cells was apparent 2 h after BAL. BAL markedly impaired the ciliary border. The mean number of cilia/microns 2 fell to 1.5 +/- 0.3/microns 2, then gradually rose to 7.5 +/- 0.5/microns 2 (controls 9.7 +/- 0.5/microns 2). The morphological signs of impairment of the self-cleaning ability of the epithelium were the most pronounced after 24 h and were still present at the end of the experiment.

Animals↗

Elastin content in human fibrotic and cirrhotic liver.

Human liver tissue obtained at autopsy was extracted with hot 0.1 M NaOH. Determination of amino acids desmosine and isodesmosine was used to quantify elastin in the insoluble residue. Hydroxyproline content was used as an index of collagen content in the liver. Hydroxyproline content was twofold in fibrotic liver and threefold in cirrhotic liver when compared to normal liver, while the sum of desmosine and isodesmosine increased threefold and sixfold, respectively. Elastin content is low in normal liver when compared to collagen but appears to grow much faster in diseased liver.

Aged↗

[Tracheobronchography in neonates and infants with obstruction of the upper respiratory tract].

In the period of 1980 to 1989 the authors performed contrast examinations of tracheobronchial tree in 38 children up to one year of age, three of them being newborns. In 29 examined children (74.4%) there was an anatomical defect causing the obstruction of upper respiratory pathways. In 15 of them the trachea compression was caused by pressure of hyperplastic thymus on the brachiocephalic arterial truncus crossing trachea. For visualization of upper respiratory pathways Hexabrix 320 (Byk Gulden) was used in 30 children, administered in 10 cases by jet ventilation. The filling was recorded by radiocinematographic method.

Bronchography↗

Regeneration of changes produced in rabbit tracheal epithelium by saline lavage of the airways.

The authors studied the course of the repair of changes induced in the rabbit tracheal epithelium by saline lavage of the airways. The tracheal epithelium was examined 2, 24, 48 and 72 hours after treatment. Saline lavage stimulated the goblet cells to instantaneous discharge of their secretion. 2 hours after treatment 98 +/- 3% of the goblet cells were completely exhausted and had degenerated. Repair of the changes began 24 hours after lavage and was associated with massive differentiation of new goblet cells resulting in hyperplasia of the mucus-secreting elements with formation of endoepithelial mucous glands. The most pronounced injury to the ciliated cells was apparent 2 hours after lavage, then the degree of alteration of these cells gradually decreased. Saline lavage markedly impaired the ciliary border. The mean number of kinocilia per micron2 fell to 1.5 +/- 0.3. In subsequent phases the number of kinocilia rose gradually to 7.5 +/- 0.5/micron2. This value was still significantly lower (P less than 0.005) compared with controls. The first signs of impairment of the self-cleaning ability of the epithelium were recorded 2 hours after lavage. The most pronounced disturbances of the mucus flow were observed after 24 hours. At the end of the experimental period small clumps of condensed mucus and rather numerous bacteria were still present in the area of the ciliary border.

Animals↗

Ultrastructure of bronchial submucosal glands in children with chronic respiratory diseases.

The ultrastructure of bronchial submucosal glands in 4 children with chronic respiratory diseases was studied. Based on their ultrastructure the glandular secretory cells were divided into four categories: 1. mucous cells packed with large electron-lucent coalescing granules with fibrogranular matrix, 2. mucous-like cells with abundant granular endoplasmic reticulum and fewer smaller electron-lucent granules, 3. serous cells containing small to moderately large membrane-bound electron-dense granules with homogenous matrix and prominent granular endoplasmic reticulum, 4. sero-mucous cells similar to the serous ones but containing granules of either serous or mucous morphology. In our patients the mucous and mucous-like cells prevailed, forming 54.6%-100% of the glands' secretory area. Only in 2 children all four types of secretory cells were detected. Signs of pathological alteration were discovered in secretory cells of all patients. The system of intra- and interlobular ducts was lined by tall mucous cells.

Adolescent↗

Kinetics of 3H-thymidine label in rat liver regenerating after partial hepatectomy and after damage with carbon tetrachloride or silica.

Rat liver DNA was labelled with [methyl-3H] thymidine after partial hepatectomy, carbon tetrachloride poisoning, or an intravenous injection of silica dust. Changes in DNA labelling were studied for 4 weeks after the single pulse. Total radioactivity incorporated into liver DNA after partial hepatectomy and after carbon tetrachloride administration remained on the same level when compared with that found after 1 h. DNA activity in liver of untreated rats and of rats treated with silica decreased by about 50% within the first 2 weeks and then remained on this level for the rest of the studied period. These differences may reflect the fact that hepatocytes that have a long life span are preferentially labelled in partially hepatectomized and CCl4-treated rats, while liver macrophages with a short half-life take up a large part of the label in intact rats and in rats treated with silica.

Animals↗

Ultrastructure of rabbit tracheal epithelium after saline lavage of the airways.

In experiment the effect of saline lavage on the ultrastructure of the tracheal epithelium was investigated. Immediately after this procedure the trachea was lined with markedly altered pseudostratified columnar epithelium with remnants of the ciliary border. The intercellular spaces were markedly dilated, but the apical junctional complexes were left intact. 99% of the goblet cells were exhausted degenerated and were gradually expelled from the epithelium. Damage to the ciliated cells was not so generalized but some of them displayed signs of vacuolar degeneration. The ciliary border was severely impaired with only 1.5 kinocilia/microns 2, but the majority of remaining cilia were intact. Compared with controls there was only mild, but significant increase in the number of degenerating and malformed cilia. Morphological signs of impaired self-cleaning ability of the epithelium were not noticed.

Animals↗

Elastin powder produced for cosmetic purposes does not affect formation of granulation tissue.

A suspension of elastin powder that is produced for cosmetic purposes has been applied on open skin wounds made in rats. Elastin particles (diameter smaller than 0.1 mm) prepared by extraction of bovine nuchal ligament with alkali had no effect on wet weight and dry weight of granulation tissue formed in the wound within 6 days. Hydroxyproline content which indicates collagen content of the granulation tissue was not also changed.

Animals↗