Biomedical subjects
Publications and source records attributed to I Nikolov.
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The activity of polyamine oxidase (PAO) in rat tissues, and its subcellular distribution, were assayed using a simple polarographic method. The highest PAO activity was measured in the liver and the lowest in the skeletal muscle. In liver, kidney and uterus the highest specific PAO activity was found in the light mitochondrial fraction. PAO was not found in the microsomal fraction except in the kidney.
Ochratoxin A has been detected more frequently and at higher levels as a contaminant in staple food consumed by subjects affected by Balkan endemic nephropathy or urinary tract tumours in the Vratza district (Bulgaria) than in samples from control populations in and outside the endemic area. Serum from patients with Balkan endemic nephropathy also contained ochratoxin A more frequently and at higher levels than serum from controls. Metabolic phenotyping of subjects in the Vratza district with debrisoquine revealed a preponderance of extensive metabolizers among subjects at high risk for Balkan endemic nephropathy. In rats, ochratoxin A is metabolized to 4-hydroxyochratoxin A, and rat strains shown to be poor or extensive metabolizers of debrisoquine were also poor or extensive metabolizers of ochratoxin A. In order to determine whether the metabolic phenotype for debrisoquine also parallels that of ochratoxin A in humans, a sensitive method was developed for quantifying ochratoxin A and its 4-hydroxy metabolite in human urine. This method was subsequently used to analyse urine from subjects who had previously been phenotyped for debrisoquine. Ochratoxin A was detected more frequently and at higher levels in urine from members of families affected by Balkan endemic nephropathy than in samples taken from subjects in control areas. No 4-hydroxyochratoxin A was found in any of these samples (detection limit, 15 ng/l urine). On the basis of results from human studies and animal models, the role of genetic polymorphism in drug oxidation and disease susceptibility is discussed briefly.
The activity of polyamine oxidase (PAO) participating in the intracellular catabolitic interconversion of the polyamines and the total concentration of polyamines in some tissues of hamsters with transplantational pigmented melamoma IC-Sofia were studied. The experiments were carried out on day 0, as well as on the 11th, 15th, 21st and 27th day after the tumor transplantation. The PAO activity and the polyamine concentration were determined in tumor tissue (with the exception of day 0), in the liver, kidneys, lung and serum (without PAO). A gradual decrease of the PAO activity and a marked rise in the total concentration of polyamines were observed in the growing tumor. In the remaining tissues the PAO activity initially rose slightly until the 15th day, then dropped, whereas the polyamine concentration increased all the time. The dynamics of the enzyme activity and the polyamine concentration were most pronounced in the lung. Tumor growth was not accompanied by changes in the polyamine concentration in the serum.
Investigated were 16 pregnant merino sheep, 5-7 years old with active weight 50 kg, divided into two groups--control and experimental. The experimental group was fed with forage, containing 0.65 nitrates from the dry substance of the ration. It was established that the elimination of part of the taken with the forage nitrates is realized through the milk. Traced were the periods of substitution of the fetal haemoglobin with adult in new-born lambs, and the influence of the liberated with the milk nitrates, taken by the sucking lambs, on the quantity of the methemoglobin.
Experimental researches were carried out on sheep, fed with forage, containing 0.6% nitrate in the dry substance of the ration with the aim to follow the dynamics of the thyroid hormones, respectively the functions of the thyroid gland and its connection with some hematologic and biochemical indexes in the blood (methaemoglobin, blood sugar, carotene and vitamin A). It is ascertained that T3 and T4 decrease during the development of chronic nitrate poisoning, and the blood sugar and methaemoglobin are increased. The quantity of carotene and vitamin A is decreased, as a hypovitaminosis condition of the animal organism is achieved.
Investigations were carried out with pigs divided into four groups and treated with monensin-Na at rates of 20, 30, and 50 mg/kg, once only, through a nose-pharyngeal tube. The total change in the clinical status was followed up. Most characteristic were found to be the changes setting in with the posture and locomotive apparatus--prolonged lying, pareses, etc. Blood was checked in the dynamic course of the disease at the 4th and the 24th hour as well as on the 6th day following monensin-Na treatment. The amount of haemoglobin and the erythrocyte count rose in the early stage of intoxication, and came back to normal after the 24 th hour. Leukocytosis with neutrophilia was also found. The serum level of selenium, calcium, vitamins A, B1, and C dropped substantially, while that of phosphorus and magnesium rose. The morphologic changes were found to be localized in the parenchymal organs and in the skeletal muscles. Featuring were diffuse hyperaemia, haemorrhages, granular degeneration, and focal necrosis.
A total of 108 cows were gynecologically investigated. Twenty-four of them were found to be suitable as donors. These were within the range of the 40th to the 60th day following calving, were not inseminated, and had no complications at calving and over the puerperal period. Estrus was synchronized via implants (3 mg norgestomet Synchromate B, Intervet in s/c application); 8 days later the donors were injected with 3000 IU PMSG each in order to induce superovulation. On the 10th day the implants were removed, and each animal was injected with 22 mg prostaglandin F3 alpha. At the 24th hour following the onset of estrus half of the donors were injected with anti-PMSG (i/v). It was found that the capacity of cows to respond with superovulation after hormonal treatment was quite individual. The application of antigonadotropic sera on the first day of estrus limited superovulation and raised the number of fertilized ova, resp., of embryos able to be transplanted. It was demonstrated also that to shorten the period from washing the uterus up to the impregnation of the donor animals it is necessary to apply hormonal therapy and preventive measures in dependence on the functional and morphologic state of the ovaries and the sexual apparatus.
Studied was the effect of some hormonal preparations--progesteron, GnRH, and HCG with progesteron--injected immediately prior to artificial insemination on the reproductional functions of cows raised under industrial conditions. It was found that the conception rate of cows at first insemination was highest upon treatment with GnRH--67.86 percent, i.e., by 14.29 percent higher than that of the control group. The same trend remained with the total conception rate. Lowest was the use of pellets per cow--1.33--with animals treated with GnRH prior to insemination. The application of GnRH (Berlin Chemie, GDR) was sufficiently effective at single i/m injection before artificial insemination. It could be employed to raise conception rate as well as to lower the use of pellets for impregnation of cows.
The radioprotective effect of the Bulgarian drug Adeturone was tested on prolonged irradiated monkeys. The animals were gamma-irradiated (137Cs) in a dose of 8.3 Gy (exposure rate 3.95 X 10(-3) mA.kg-1; (0.92 R.min-1]. Adeturone, given by i.v. injection at a dose of 100 mg.kg-1 body weight according to a pre- and postradiation scheme will afford protection to monkeys by ensuring 50% survival and mitigating the severity of some symptoms of radiation disease. A similar effect was obtained with ATP-administration by two i.m. injections of 37 mg.kg-1 body weight. The survival in control group was only 5% (LD95/45).
The free radical 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl (TMPO) was injected i.p. in doses of 100 mg/kg bw into Syrian hamsters: untreated, partially hepatectomized and grafted with transplantable tumours as well as into mice with B16 melanotic melanoma or with an adenocarcinoma. One hour after application of the compound its content was determined spectrometrically in livers, kidneys, lungs and all tumours. The characteristic triplet signal of TMPO was registered in the hamster and mouse melanotic melanomas but not in all other animal tissues and tumours. This may be the result of an enzyme defect in the melanotic melanoma cells or of a retention of TMPO by melanin. It was also found that TMPO is metabolized predominantly in the livers of the animals.
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