Biomedical subjects
Publications and source records attributed to A V Glazunov.
The subjects of the study were 112 patients with rheumatic polymyalgia (RPM) and giant-cell arteritis (GSA). The study shows that RPM and GSA are complicated by cerebral flow disturbances and myocardial infarction. Therapy with prednisolone and non-steroid antiinflammatory drugs reduces the risk of these complications and lethal outcome in patients with RPM and GSA.
The authors have studied efficacy of various antibacterial drugs in reactive arthritis (RA). A comparative randomized trial was made of efficacy of doxocycline (DC) in a dose 200 mg/day, erythromycin (EM) in a dose 2 g/day, co-trimoxazole (CT) in a dose 1920 mg/day, cyprofloxacin (CF) in a dose 1 g/day in 79 RA patients. Each of the drug was given as two three-week courses with a 3-week interval. The patients were followed up for 12 months. The assessment of the drugs effect on the articular syndrome and the symptoms of the infectious focus was made with the use of computer questionnaire. 3-month remission was achieved in 9 DC patients (43%), 5 EM patients (24%), 6 CF patients (32%) and only in one CT patient (6%). Suppression of the infectious foci was similar for all the drugs tested during the follow-up period. Within the first three months of the trial DC had significant advantages over the other antibiotics in management of the articular syndrome. CF was highly effective (p < 0.001) in patients with RA running up to one year. The conclusion is made that suppression of the symptoms of the focal infection is not sufficient for RA effective treatment, antibiotics vary significantly by their effect on the course of the articular process.
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65 patients with knee and hip joints osteoarthrosis with concomitant urinary infection and/or irritable colon syndrome were randomized into three groups: group 1 (21 patients) received doxicyclin 200 mg/day with nistatine for three weeks with 3-week interval between the courses and bifidum-bacterin administration between the courses and after the treatment; group 2 (22 patients) received biseptol 1920 mg for 3 weeks then 960 mg 10 days a month; group 3 (22 patients) consisted of controls who received no antibacterial drugs. The effect was assessed upon randomization, 3 weeks, 3, 6 and 12 months after the treatment. It was established that antibacterial treatment not only attenuated dysuria and dyspepsia but also had a significant positive effect on osteoarthrosis especially in patients with x-ray stage II, allowed to reduce doses of nonsteroid antiinflammatory drugs. Further studies will help specify the role of the infection factor in development of osteoarthrosis and potential of antibacterial treatment.
AIM: To study antianginal effectiveness of trimetazidine (TMS) in monotherapy and combined antianginal therapy; to design approaches to prediction of its effect. MATERIAL AND METHODS: An open cross-over randomised trial enrolled 29 anginal patients. They were given a single TMS dose (60 mg) and its effect was compared to that of placebo, propranolol, verapamil, isosorbide dinitrate, nifedipine). The effect was estimated by an increment of bicycle exercise (BE) duration necessary to depress ST segment by 1 mm. 10 patients retained signs of myocardial ischemia at BE though they were treated with specially selected antianginal drugs. In them, we assessed additional benefit of adjuvant TMS. The drugs were tried under acute test and one-month treatment. RESULTS: In acute test a significant antianginal effects of TMS were registered against the placebo. Differences in efficiency of the antianginal drugs were insignificant. The addition of TMS to the selected drugs gave rise to the trend to prolongation of time to ST segment depression by 1 mm. We found a strong correlation between TMS efficiency in acute pharmacological test and in long-term administration. This enables using BE for prediction of long-term effect of the drug. CONCLUSION: TMS has a significant antianginal effect. It is especially beneficial in cases of insufficient effectiveness of conventional antianginal drugs or when their use is problematic because of marked disturbances of hemodynamics.
In our previous works, a mutation in the RAD57 gene was shown to induce the plasmid DNA double-strand gap (DSG) repair via a special recombinational repair mechanism: homolog-dependent ligation responsible for reuniting disrupted plasmid ends without reconstructing the sequence lost because of the DSG. In this work, the role of the RAD55 gene in the plasmid DNA DSG repair was studied. A cold-sensitive rad55-3 mutation markedly decreased the precision of plasmid DNA DSG repair under conditions of restrictive temperature (23 degrees C): only 5-7% of plasmids can repair DSG, whereas under permissive conditions (36 degrees C), DSGs were repaired in approximately 50% of the cells. In the cold-sensitive mutation rad57-1, the proportion of plasmids in which DSGs were repaired was nearly the same under both permissive and restrictive conditions (5-10%). The results indicate that a disturbance in the function of the RAD55 gene, as in the RAD57 gene, leads to a drastic increase in the contribution of homolog-dependent ligation to the repair of double-strand DNA breaks.
DNA double-strand breaks (DSB) are the most dangerous damage to genetic material caused by ionizing radiation and some chemical agents. Nonrestored DSB lead to chromosomal rearrangements, genetic instability, and cell death. On the other hand, DSB normally occur in cells in the course of normal gene functioning. DSB repair not only protects cells from adverse consequences and maintains stability of genetic material but is directly involved in the most important processes of cell life, such as meiosis and humoral immunity in vertebrates. The diverse mechanisms of homologous and nonhomologous recombination underlie DSB repair. In this respect, yeast are the best-studied object. In this review, genetic control and molecular models of the recombination DNA DSB repair in Saccharomyces cerevisiae are considered. Evidence has accumulated that indicates the higher eukaryotes retained the basic set of the repair pathways characteristic of bacteria and lower eukaryotes. However, different repair mechanisms predominate in yeast as compared to higher eukaryotes. Therefore, the results obtained in yeast experiments may be applicable to higher eukaryotes.
The linearized plasmid with complementary (cohesive) ends was shown to restore the circular form in cells of the rad57 mutant with a lower efficiency than in Rad+ cells. This process proved to be cold-sensitive in mutant cells, in contrast to wild-type cells. When mutant cells were shifted from 23 up to 36 degrees C, the repair efficiency increased approximately 1.5 times. In most cases examined, the repair was not accompanied by the doublestrand gap repair within the break site and did not depend on temperature. Homology between chromosomal and plasmid DNA sequences in the break region and the presence of cohesive ends were shown to be essential for the repair of linearized plasmids with a double-strand gap in cells of the rad57 mutant. Degradation of cohesive ends of the linearized plasmid during its repair in rad57 cells is insignificant. Possible mechanisms of linearized plasmid repair in the rad57 mutant are proposed.
The authors report 4 cases with hepatitis C infection running with vascular disorders: Raynaud syndrome (3 cases), mixed cryoglobulinemia (1 case), primary pulmonary hypertension (1 patient). Whether hepatitis C virus contributes to vascular disturbances is discussed and relevant literature is reviewed.
20 mg of nifedipine, 160 mg of verapamil and 120 mg of diltiazem were given to 53 patients aged 60-90 (33 males and 20 females) with stable angina pectoris and painless myocardial ischemia. Bicycle exercise tests employed to evaluate antianginal activity of the above drugs showed them to significantly prolong the period of exercise free of a 1-mm depression of the ST segment. This was true both for males and females. In females nifedipine produced the weakest effect. Anti-ischemic activity of the drugs appeared to depend on the presence of arterial hypertension and voltage signs of left ventricular hypertrophy, initial exercise tolerance and heart rate, blood triglyceride concentrations, left ventricular end-diastolic volume, the size of the left atrium, interventricular septum thickness, etc. To prognosticate the effect of each of the 3 drugs as well as nifedipine paradoxical action in some patients the authors propose to use classification trees, providing a significant branching virtually in all relevant points.
A questionnaire survey covered 11 females with temporal arteritis (CA) and 20 healthy controls. Gastrointestinal, joint and spinal complaints were significantly more frequent in CA patients. Clinical characteristics of joint and spinal disorders in CA patients are close to those of chronic reactive arthritis. It is suggested that Horton's disease may be lacking as a stage of the infectious process in elderly patients (chronic intestinal and/or urinary infection-reactive arthritis-CA). A case is reported where CA developed after intestinal and urinary infection. Administration of antibiotics for treatment of the recurrence induced a continuous remission under reduced doses of glucocorticoids. In another case biseptol + glucocorticoids brought about a persistent remission allowing glucocorticoid discontinuation.
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Twenty-two patients with coronary heart disease (CHD) were examined for pain threshold and pain tolerance by a tourniquet test. The relationships between pain and ST segment depression were studied simultaneously during bicycle exercise. Pain sensitivity was measured in response to action of various antianginal drugs (isosorbide dinitrate, verapamil, nifedipine, diltiazem, propranolol, atenolol) and placebo. Reproducibility of the tourniquet test proved satisfactory. There were significant correlations between tourniquet test evidence and clinical patterns of ischemic myocardial episodes: significant differences in the values of pain threshold and pain tolerance in patients with painful myocardial ischemia, in combination of angina of effort with painless myocardial ischemia (p < 0.0001). Significant were also correlations between tourniquet test findings at bicycle exercise and value describing the proportion of ST depression to pain. As for the drugs, verapamil appeared most active in the tourniquet test (p < 0.02 and p < 0.05 for pain threshold and pain tolerance, respectively). Pain tolerance changes due to isosorbide dinitrate were somewhat greater than for placebo (p = 0.06). The study provided evidence in support of the adequacy of the tourniquet test for assessment of general pain sensitivity and pain sensitivity to myocardial ischemia as well as of analgetic effects of the drugs. Verapamil and isosorbide dinitrate are suggested to have analgetic activity.
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The exposure to ionizing radiation of radiosensitive mutants of diploid yeast Saccharomyces cerevisiae deficient in double-strand break repair results in formation of morphologically unstable colonies. Some characteristics of this process were studied. The results obtained are consistent with the hypothesis on relationship between DNA double-strand breaks or their repair with the formation of unstable clones of diploid yeast cells.
Isogenic diploid cells of Saccharomyces cerevisiae are more sensitive to hyperthermic treatment (50 degrees C) than haploid ones, the posthyperthermical recovery efficiency being the same for both the cell types. In contrast to this, thermosensitivity of haploid and diploid cells of Pichia pinus does not practically differ, the posthyperthermic recovery efficiency for both the cell types being also the same. It is shown that diploid cells of P. pinus in the logarithmic phase of their growth are incapable of recovering after hyperthermal treatment, which is largely the reason for their higher sensitivity to such a treatment as compared with cells in the stationary phase of growth.
The repair of a double strand gap in plasmid DNA in radiosensitive mutants of Saccharomyces cerevisiae has been studied. The proportion of repair events resulting in the complete doublestrand gap recovery of the plasmid DNA has been found to be close to 100% in Rad+ cells. The mutation rad55 did not interfere in the doublestrand gap repair efficiency and accuracy. The mutant rad57 is capable of the effective doublestrand gap repair without restoration of the DNA sequence deleted by the gap. The mutation rad53 substantially inhibited the efficiency of the doublestrand gap repair but did not influence the accuracy of the repair. Plasmid DNA doublestranded gap repair is completely blocked by mutations rad50 and rad54.
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