Mathematical models of strontium-90 behavior in a "water--fresh-water fish spawn" system in several individual cases of radionuclide entry into bodies of water

A group of 72 gilts, aged between eight and nine months, were treated 20 days each by administration of 5 g Suisynchronpr?mix (Zinc Metallibur/Sui), followed by 24-hour treatment with 750 IU PMS (Prolosanserum). Fifty per cent of the group received 500 IU per animal of HCG (Gonabion) at 11 a.m., on the fourth day after Sui. All animals were artificially inseminated at 3.30 p.m. on the fifth day after Sui. and at 7.30 a.m. on the sixth day after Sui. Laparotomy was performed on 50 per cent of the HCG-treated and untreated animals in the afternoon of the sixth day after Sui. Animals with no recordable ovulation had to undergo another laparotomy in the morning of the seventh day. The above approach resulted in regrouping by four therapeutic categories: 1. HCG with laparotomy, 2. No HCG, 3. HCG with no laparotomy, 4. No HCG and no laparotomy. In the afternoon of the sixth day after Sui (51-56 hours after HCG) ovulation had begun in all 17 measurable animals of the first group, but only in one of 18 animals of the second. The animals were slaughtered between the seventh and twelfth days after Sui, and the following ovulation percentages were established: 100 per cent in the first group, 83.3 per cent in the second, 55.6 per cent in the third, and 72.2 per cent in the fourth. The animals that had been given HCG treatment (Groups 1 and 3) were found to be superior in terms of percentual ovulation to the untreated animals (Groups 2 and 4). However, Group 2 was the only group that had been exposed to the extraordinary stress of two laparotomies, and this should be borne in mind for evaluation. Ovarian cysts (more than 10 mm) began to develop on the eighth day on the laparotomised groups (1 and 2) and on the tenth day on the non-laparotomized groups (3 and 4). Cysts developed in 41.1 per cent of all animals in Group 1, 38.9 per cent in Group 2, 27.8 per cent in Group 3, and 22.2 per cent in Group 4. Therefore, cyst formation is thought to have been stimulated by laparotomy. Ovocyte tests suggested fertilisation of all animals in the first group. The embryonation rates of the second, third, and fourth groups are discussed with reference to the dates of insemination.     

Functional role of vacuolization of the T-system of skeletal muscle fibers

T-tubules of skeletal muscle fibres easily transform into large vacuoles under the influence of various factors. These include osmotic shock produced by the efflux of small molecular weight molecules (e.g. glycerol), hypertonic shock, muscle fatigue and muscle damage. In most cases, vacuolation is reversible but the molecular mechanisms involved are not clear. Also, the functional role of reversible vacuolation has not been established. However, three possibilities may be considered. (1) Redistribution of ions and water between the cytoplasm and the extracellular space comprised by the T-system. Thus, the formation of large vacuoles may be a mechanisms for rapid osmoregulation that corresponds to regulated volume decrease in other types of cell. However, in our hands, inhibitors of various pathways that participate in volume regulation had no effect on reversible vacuolation. (2) Resealing of mechanical damage of the plasma membrane. This is usually accompanied by the development near the damaged membrane of numerous vacuoles which we have observed by confocal microscopy and use of a hydrophobic dye (RH414), to arise in part from T-tubules. (3) By confocal microscopy, it has also been shown that extracellular fluorescein dextran (Mr = 10,000), and both plasmid DNA (pUC18) and sonicated high molecular weight DNA stained with YOYO, enter vacuoles derived from T-tubules. This finding may indicate that reversible vacuolation, in the absence of membrane damage, could provide a pathway from the extracellular environment to the cytoplasm that is additional or complimentary to endocytosis; it may also be particularly relevant to the ability of muscle to be transfected by the direct injection of DNA. These several observations strongly indicate that the function of the T-system in skeletal muscle fibers is not restricted to excitation-contraction coupling.     

The first original Russian class-III antiarrhythmic nibentan

The paper presents experimental and clinical findings of the new antiarrhythmic drug nibentan. The agent was found to be a class-III antiarrhythmic agent in terms of its electrophysiological effects and an inhibitor of the delayed rectifier potassium current in terms of its effects on the ionic channels of cardiomyocytes. The clinical trial of nibentan shows that the drug is highly effective (in 70-100% of cases) in patients with atrial flutter and fibrillation and in those with supraventricular tachycardia and it is less effective in suppressing ventricular premature contractions and tachycardia. The rate of arrhythmogenic effects produced by the drug was inversely related to its antiarrhythmic action. Nibentan has been approved for clinical use.     

Modulation of the antitumor activity of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosoure a by O(6)-methyl-2'-deoxyguanosine--a new inhibitor of O(6)-alkylguanine-DNA-alkyltransferase

O6-Methyl-2'-deoxyguanosine (O6-MedG), a novel inhibitor of O6-alkylguanine-DNA alkyltransferase (O6-AGT), has been synthesized. The ability of O6-MedG to deplete the O6-AGT activity in leukemia L1210 and melanoma B16 cells in vivo has been studied. After intraperitoneal administration of O6-MedG to mice bearing leukemia L1210 or melanoma B16, the activity of O6-AGT in tumour cells decreased by 50%. Pretreatment of leukemia L1210 bearing mice with O6-MedG (200 mg/kg) 24 hours prior to ACNU (15 mg/kg) administration resulted in six out of seven 60-day survivors. Treatment of mice with ACNU (15 mg/kg) alone increased the life span by 200%. Treatment of melanoma B16 bearing mice with O6-MedG and 3 hours thereafter with ACNU resulted in a 50% inhibition of tumour growth, whereas the inhibiting effect of ACNU alone was 16%. There was no difference in leukemia growth when L1210/BCNU bearing mice were treated with O6-MedG followed by ACNU treatment. In vivo ACNU (15 mg/kg) produced a deep and prolonged inhibition of DNA, RNA and protein synthesis in leukemia L1210 cells. The DNA synthesis in leukemia L1210/BCNU cells was shown to recover more rapidly than in L1210 cells. The activities of DNA-polymerases alpha and beta and, especially, of O6-AGT were elevated in ACNU-resistant leukemia cells as compared with ACNU-sensitive cells. The activation of some repairing enzymes, such as O6-AGT, DNA-polymerases alpha and beta as well as increased levels of GSH may play a role in the development of drug resistance to ACNU.