Genotoxicity of the Bulgarian drug gastrophensin was studied by using a battery of two genotoxicity assays "in vitro" - Salmonella/mutation assay and "in vivo" - the rodent bone marrow micronucleus test. Mutagenicity of water solution of gastrophensin towards Salmonella "in vitro" - the rodent bone marrow micronucleus test. Mutagenicity of water solution of gastrophensin towards Salmonella "in vitro" was tested in five mutant, histidine auxotrophic strains - TA 1535, TA 1537, TA 1538, TA 98 and TA 100 without and in the presence of metabolic activation (+/- S9) at concentration of 0.4, 2 and 10 mg center dot ml-1. Gastrophensin did not induce mutagenic response in the Salmonella/mutation assay in a range of tested concentrations in both series of assays (+/- S9). Gastrophensin did not induce micronuclei in bone marrow cells of male C57Bl6 mice at 24, 48 and 72 hours after single oral treatment with 236 mg center dot kg-1 (80% DL50 oral, mice) and 118 mg center dot kg-1 (40% DL50 oral, mice). Based on the present data a conclusion of the lack of mutagenicity and of carcinogenic potency of gastrophensin was made.
The rabbit pancreatic structure at histological and ultrastructural level, in different intervals after ligature of pancreatic duct, was studied. Changes in the exo- and endocrine parenchyma were observed. Canalicular structures and conjunctive tissue replace the destroyed acinar cells. In some of the islets the B cells are degranulated or necrotic. Some islets contain infiltrations of lymphocytes, macrophages and granulocytes. Cavities formed by necrotic endocrine cells could appear. The A and B cells proliferation is observed in the new-formed clusters of endocrine cells and ductless. The mechanism of this process is similar to that of the islet formation during the embryonic development or in nesidioblastosis, but they are never transformed in the definitive islet of Langerhans.
A Growth-related protein kinase's activity was studied in clinically affected and unaffected psoriatic epidermis. This activity was about 3 fold higher in clinically affected skin. Additionally, the unaffected psoriatic epidermis shows higher activity than the normal one. We conclude that the Growth-related protein kinase might be involved in the pathogenesis of psoriasis.
30 different lots (batches) of insulin substances ("Pharmachim" Ltd.) are analysed and the contents of somatostatin is established. The middle quantitative values and the standard deviations are specific. Though that monocomponent and bovine conventional insulin substances pertain to groups of different purity they exhibit highest purity but also greatest variability, while single-peak and porcine conventional insulins show less purity but these groups are more homogenous.
The authors examined the liver of 20 rabbits "Newzeland white" and "Chinchila", undergone atherogenic diet with cholesterol (0.3-0.5 g/kg body weight) for 30 and 60 days. They determined cholesterol, lipids, triglicerides and beta-lipoproteins in the serum. The morphologic study revealed accumulation of cholesterol in the hepatocytes, fibrosis, proliferation of the bile ducts and signs of hepatic cirrhosis.
In order to establish the polarizing microscopical characteristics of collagen in preserved dura mater transplants and in controls, a study was performed. Attempt was made for an intrpretation of velocity of collagen rehydratation by means of data of total anisotropy. The results show a faster rehydratation of collagen fibrils in control (unpreserved) dura mater. Changes in the velocity of rehydratation of collagen fibrils in lyophilized dura mater were connected with structural changes during lyophilization. The most appropriate period of time for rehydratation of lyophilized dura mater transplant was determined from the results of the polarizing microscopical study.
The contents of glucagon in insulin substances ("Pharmachim" Ltd.) is determined in accordance to the needs of pharmaceutical production. The middle quantitative values and standart deviation are specified. Nevertheless that monocomponent and bovine conventional insulin substances pertain to groups of different purity they exibit the highest purity. Bovine conventional insulins exibit the greatest variability, while monocomponent insulins are destinctively homogenous. Single-peak insulin substances exhibit less purity, but this group is more homogenous. The middle quantitative value is within the admissible limitations. Porcine conventional insulins have high contents of glucagon as well as high values of standard deviation.
The authors studied light- and electronmicroscopically the lungs of 20 rats after experimental burns in closed space. Twenty one histological parameters were evaluated. Two mechanisms of quickly developed fatal outcome were established--asphyxia and acute injury of shock lung. Electronmicroscopically there was an increased secretion of surface active materials and degenerative changes in the alveolar epithelium and capillary endothelium. Carbon particles found in the upper respiratory tract were considered as signs of vitality.
Pit cells are morphological equivalent of large granular lymphocytes with NK activity. The aim of our study is to define the morphological changes of pit cells in the liver of the rat after stimulation with the biological response modifier Polyerga. Polyerga was applied intramuscularly in a single dose of 6 mu g per kg body weight. The animals were perfused on the 24-th hour, 48-th hour, on the 4-th day and on the 7-th day after injection. The perfusion was done through the portal vein and the liver was processed for electron microscopical cytochemistry for endogeneous peroxidase demonstration. A 3-to-4-fold increase in the number of pit cells was observed within a period of 1 to 4 days after injection. Pit cell granules were negative for endogeneous peroxidase. After Polyerga stimulation pit cells showed a tendency of orientation of their organelles toward the contact area with Kupffer and endothelial cells. These changes are considered to represent the morphological expression of rat liver pit cell activation.
The aim of the study is to examine influence of r-Hu-Ero on megakaryocytopoiesis in rats with depressed by dialysable substances thrombocytopoiesis. Experimental animals are male Wistar rats, treated with bidestilled water, used dialysis solution and r-Hu-Ero. We investigate bone marrow of experimental rats. More expressed increase of megakaryocyte count "pro mile" in rats with depressed megakaryocytopoiesis, as well as influence on megakaryocyte maturation for shorter period of time, provide evidence to be accepted that megakaryocytopoiesis, depressed by dialysable substances is more sensitive to stimulating effect of r-Hu-Ero. The reason for this enhanced sensitivity at present appear unclear.
The aim of the present study was to elucidate the correlation between the Renin secretion and increased Plasma Calcium concentration and the role of Calmodulin in this process. Plasma Renin activity was determined radioimmunologically in 31 white rats, that were grouped as follows: group I - 7 controls loaded for 6 days perorally with 0.5 ml/200 g b.w. glycerin and injected i.m. for 6 days with 0.1 ml/200 g b.w. with 0.9% NaCl; group II - 8 rats, treated for 6 days with Tachistin 0.0025 mg/200 g b.w., dissolved in glycerin 0.5 ml/200 g b.w.; group III - 5 rats, treated with Tachistin 0.005 mg/200 g b.w. in the same manner; group IV - 5 rats injected i.m. with Chlorazin 0.5 mg/200 g b.w. for 6 days; group V - 6 rats, loaded with double dose Tachistin and with Chlorazin 0.5 mg/200 g b.w. for 6 days. Blood samples were taken intracardially on the seventh day from the beginning of the experiment and were analyzed with kits of Sorin-Biomedica-Italy. Our results suggest that the hypercalcemia induced by Tachistin caused a dose-dependent increase of PRA and Ca-Calmodulin complex is the dominant second messenger of Renin secretion.
The effect of acute and chronic ASA administration on stomach and duodenal mucosa was studied on white male Wistar rats. ASA (250 mg/kg b.w.) was administered by esophageal intubation in a single dose, and the rats were sacrificed at 2, 6, 24 hours, or after two, three, ten and twenty days, 24 hours after the last ASA application. Two types of erosions were found in the first 24 hours: superficial and deep. Superficial erosions showed advanced healing by the 24th hour. Deep erosions appearing between 6 and 24 hours from the beginning of experiment became deeper, after two and three days ASA application. They had morphological features of chronic ones by the 10-20th day. ASA resorbtion was most expressed by the 3rd day from the experimental onset (plasma concentration 0.348 +/- 0.052 g/l). The resorbtion was decreased in chronic experiment, and plasma concentration (0.236 +/- 0.046 g/l, 0.244 +/- 0.045 g/l) showed statistically reliable lower values.
The early ultrastructural changes in type 2 pneumocytes (PN2) as a result of burn and endotoxic shock in rats and rabbits were studied. Stereotype morphological damages in PN2 were established. Differences between experimental models were quantitative and depend mainly from the severity of shock and animals species. Morphofunctional heterogenity of PN2 population leads to the appearance of three groups of PN2: 1) PN2 with degenerative changes; 2) PN2 with "stress" hyperactivity and exocytosis of lamelar bodies; and 3) PN2 with increased number of lamelar bodies. Disturbances of lamelar bodies morphogenesis (conglomerates, giant lamelar bodies) as well as lamelar bodies formation by alternative way - directly from rough endoplasmic reticulum were observed. The predominant part of the described PN2 lesins were adaptive in character.
A total of 126 white male Wistar rats under subacute conditions were studied. Of them, 76 were perorally treated with AlCl3 in a dose of 3 mg/kg b.w. daily for 40 days. Activities of acid phosphatase (AP), succinate dehydrogenase (SDH), adenosine triphosphatase (ATP-ase) and the contents of glycogen, glucoproteins and RNA were dynamically followed-up in the liver and kidney. Serum activities of ASAT and ALAT were estimated by Borhringer's tests. Morphological changes were histochemically investigated. There was an initial elevation followed by reduction mostly manifested for SDH and ATP-ase and an increase of AP at the end of trial. Histochemical data argued for disorders of protein and carbohydrate metabolism. Morphological alterations more outlined in the liver became more severe until the end of the experiment.
Experiments were carried out on longitudinal and circular smooth-muscle strips isolated from the ileum and colon of healthy dogs (controls) and of dogs with local peritonitis. The changes in the contractile responses of the strips to carbachol administered cumulatively were studied, and the EC50 and pD2 values were calculated from the dose-response curves. For the colonic longitudinal strips the EC50 was 6 x 10(-8)M and the pD2 was 7.58. The pD2 for the ileal longitudinal strips was 7.83. The pD2 value for the circular strips from the ileum and colon was 7.19 and 8.87 respectively. In the dogs with local peritonitis, the sensitivity of the longitudinal strips to carbachol was higher (the pD2 for the ileum was 7.86 and for the colon-7.21) as compared to the circular strips (the pD2 for the ileum was 6.22 and for the colon-6.65). The affinity of the cholinoreceptors in the ileal circular strips to carbachol was decreased as compared to controls.
The morphological investigation in an experimental model of lead (Pb) encephalopathy (according to the method of A. Pentschew, 1966) is presented. Electron microscopy-dense inclusions are found out in the nuclei and cytoplasm of astrocytes and in some ependyma cells in the investigated cortical and subcortical (paraventricular) structure of the brain and spinal cord. This confirms the direct toxic action of Pb on these structures and proves their participation in pathogeneses of the developing encephalopathy. The established inclusions in the ependyma and the data about a disturbance of the blood-brain barrier give a reason to be proposed the possibility for a penetration of Pb in the nervous system not only through a blood but also through a cerebrospinal fluid way.
A system is created for study of the agents, affecting the arterial pressure and baroreflectory sensitivity, which comprises:transducer for arterial pressure Statham P23 ID, connected to a polygraph Biomedica O.T.E.; eight-bite analogous-numerical transformer; microcomputer, compatible to Apple 2+; two diskette devices and printer. The arterial pressure of the lab animals (rats, rabbits, cats) is directly measured in a. carotis communis by means of the transducer and is recorded on the polygraph. For the system a computer program is designed which allows archivation of the primary experimental data; automatic and precise determination of the momentary values of the systolic and diastolic arterial pressure and intersystolic interval; determination of the baroreflectory sensitivity by means of linear regressive analyses; printing of the results under the form of diagrams and tables. By means of this system much time is spared, related to the accounting and handling of the experimental data.
4-hydroxy-3-(3-oxo-1-phenyl butyl)-2H-1-benzopyran-2-one (warfarin) has been synthesised by an original method. The influence of a phase-transfer catalyst of ammonium type with alkyl substituents containing eight carbon atoms upon the reaction of Michael addition has been investigated. It has been found out that when elongating the hydrocarbon chain of the substituents to the nitrogen atom in the quaternary ammonium salt the yield of the product decreased. The acute (LD50) and subchronic (lasting for 30 days) toxicity was determined when taking warfarin orally. The experimental data show that LD50 is 500 mg/kg for mice and 420 mg/kg body mass for rats. The subchronic toxicity at experiments made with rabbits (each day taking orally respectively 25 and 100 mg/kg) does not reveal any humoral and tissue toxic influence of warfarin. The results from the comparative cytogenetic analysis of warfarin and Niffcumar are the basis of the conclusion cytogenetic analysis of warfarin and Niffcumar are the basis of the conclusion that warfarin damages chromosomes of mice's marrow cells (used as a model) less than Niffcumar. Moreover warfarin has a slight influence on these cells in the first place changing the orientation of chromosomes one towards the other and unlike other drugs it does not damage nuclear chromatin strongly.
In the paper are considered the basic mechanisms, leading to accumulation of methemoglobin in the red blood cells. The inherited methemoglobinaemia, due to enzymatic failure of cytochrome B5-reductase is considered.
