[Delayed appearance of hypertension in spontaneously hypertensive rat (SHR) injected with CpG-rich DNA early in ontogenesis].

In this study we have investigated properties of blood serum extracellular DNA (cell-free DNA) from patients with essential arterial hypertension (AH). Cell-free DNA concentration was not changed in the control AH group compared to norma (healthy donors) but fragments of CpG-rich cell-free DNA marker content were increased at transcribed area of ribosomal repeat (TArDNA, CpG-DNA). To evaluate effect of CpG-DNA on AH development in 2-day SHR line and in control normotensive line (WKY), 700 ng of human TArDNA single subcutaneous injection were inoculated to obtain anti-CpG-DNA polyclonal antibodies. These antibodies could change CpG-DNA contents in total cell-free DNA. Blood pressure (BP) in 9-week SHR line rats immunized with CpG-DNA was equal to BP of WKY rats. Then BP of immunized SHR steadily increased with age and reached high value 8 weeks later compared to control SHR rats. Cell-free DNA analysis in 17-week SHR line rats showed significantly reduced concentrations of cell-free DNA and also showed decrease in small DNA fragments content, but increased content of CpG-DNA (rat TArDNA). These changes were accompanied with 3.5-fold blood endonuclease activity increase and decrease of free (unbound to cell-free DNA) anti-CpG-DNA antibodies quantity. Total anti-CpG-DNA antibodies quantity in immunized rats wasn't changed compared to control animals. Thus, observed effect of increase in stable BP elevation age in immunized SHR line rats doesn't relate to increase of anti-CpG-DNA antibody production. Possible reason of this effect is further discussed.

[The study of therapeutic effect of synthetic bradykinin "gene" contained in retrovirus vector on spontaneously hypertensive rats].

Administration of DNA plasmid pPS-3-neo (brd) with synthetic bradykinin " gene " to 2-days old male spontaneously hypertensive rats (SHR) leads to 2 weeks delay in development of arterial hypertension. Lowering of SBP and positive results of PCR DNA of various organs observed in synthetic bradykinin " gene " transgenic SHR but not in control SHR confirm therapeutic effect of synthetic bradykinin " gene " . This data indicate one of possible ways of gene therapy of arterial hypertension as well as other pathological states by introduction of transgene directly into genome of the organism.

[Cardiomyocyte culture as a highly sensitive system for testing pharmacological activity of specific bradycardic agents].

Two antiarrhythmic agents were studied: verapamil and bradizole, a new bradycardic drug. It was found that both drugs exhibit a dose-dependent negative chronotropic effect on the culture of contractile cardiomyocytes of newborn rats. Bradizole showed more pronounced bradycardic properties than verapamil.

[On the mechanisms of thyrocyte proliferation and death in autoimmune thyroid diseases].

Lymphocytes isolated from diffuse toxic goiter (Graves' disease, GD) stimulate the proliferation of "normal" thyrocytes (isolated from euthyroid goiter) in primary culture, and give them the properties of GD-thyrocytes (loss of sensitivity to the growth-promoting factors of FCS and lesser capacity of binding antibodies from GD patients' serum). The complement-free sera of GD patients (but not the sera of patients with Hashimoto's thyroiditis, HT) induce the death of "normal" thyrocytes more rarely than full-complement sera do. Both types of serum cytotoxicity are manifested on GD-thyrocytes much more rarely than on "normal" cells. The Fas-receptor on GD-thyrocytes in situ is expressed less than on "normal" and especially on HT-cells. The level of soluble Fas-ligand in the serum of some complement-free patients was found to be increased. These sera induce apoptosis in "normal" thyrocytes, but not in GD-cells nor in human skin fibroblasts. In the authors' opinion, the proliferation of GD-thyrocytes in situ is stimulated by intrathyroid lymphocytes, which directly stimulate this process and induce the loss of receptors which mediate the cytotoxic effects of serum factors.

[Blood serum immunoglobulins from patients with juvenile struma reduce the cAMP level in isolated human thyrocytes]. / Immunoglobuliny iz syvorotki krovi lits s iuvenil'noi strumoi snizhaiut uroven' tsAMF v izolirovannykh tireotsitakh cheloveka.

Clinico-hormonal examinations of 19 patients with juvenile struma revealed in many of them signs of latent hypothyrosis (increased age-specific level of blood serum TTH level and hyperergic reaction to TRH). Incubation of thyrocytes isolated from perinodular tissue of patients with euthyroid nodular goiter with IgG isolated from the blood serum of patients with juvenile struma resulted in a reliably lower content of cAMP in the cells than after thyrocyte incubation with IgG isolated from the blood serum of 9 healthy donors. This is indicative of the presence of thyroblocking antibodies in the blood serum of patients with juvenile struma. Though no correlation could be traced between the tested immunoglobulin activity, on the one hand, and blood serum TTH level and struma size, on the other, one may propose a contribution of thyroblocking antibodies to the pathogenesis of juvenile struma.

[Determination of autoantibodies to thyrotropin receptors in patients with diffuse toxic goiter]. / Opredelenie autoantitel k retseptoram tireotropnogo gormona u bol'nykh diffuznym toksicheskim zobom.

The blood level of antithyroid autoantibodies to TSH receptors was determined in patients with toxic goiter (TG) before and during antithyroid therapy using two biological methods (by the increment in the cAMP level in slices and primary monolayer culture of human thyroid cells) and a radioreceptor method (by inhibition of TSH binding with its receptors from the animal thyroid). Comparison of the results of these three methods has shown that all methods are almost equally valuable for diagnosis of new cases of TG. However the biological method was shown to be more sensitive and informative with regard to predicting the time of immunological remission during antithyroid therapy.

[Thyroid-stimulating autoantibodies in the blood of patients with diffuse toxic goiter]. / Tireostimuliruiushchie autoantitela v krovi bol'nykh diffuznym toksicheskim zobom.

The level of thyrostimulating autoantibodies (TSA) in IgG fraction isolated from the blood serum by precipitation of (NH4)2SO4 was determined in 36 patients with diffuse toxic goiter (DTG) and in 8 healthy donors. TCA which were assessed by a rise of the level of cAMP in human thyroid sections (obtained at operation from extranodal tissue of patients with nodal euthyroid goiter) after 2 h-incubation at 37 degrees C with IgG, were determined in 32 DTG patients (89%). The patients were divided into 2 groups with respect to their clinical and thyroid status: with a high and normal or subnormal content of the blood thyroid hormones. In the 1st group the frequency of detection (96%) and the level of TSA (570.64 +/- 109.63%) were much higher than in the 2nd group of patients (70 and 186.29 +/- 23.06%, respectively). The highest levels of TSA (1085.25 +/- 551.27%) were found in 4 of 26 patients (the 1st group) who had not received specific therapy.

[Proteinuria in diabetics before and after treatment with the Biostator apparatus]. / Issledovanie proteinurii u bol'nykh sakharnym diabetom do i posle lecehniia s pomoshch'iu apparata "Biostator".

The authors present for the first time their results concerned with the determination of selective proteinurea by disc electrophoresis in polyacrylamide gel in patients with insulin-dependent and insulin-independent diabetes mellitus with and without the clinical signs of kidney affection. A study was made of the uroproteinograms of these patients before and after the correction of carbohydrate metabolism by means of programmed insulin administration. A conclusion was made of a possibility to use the above method for early detection of diabetic nephropathies. Programmed insulin administration using the Biostator apparatus was shown to improve tubuloglomerular functions, that was expressed in the lowering of proteinurea and in some cases in the improving of the qualitative composition of uroproteins.

[Effect of thyrostatic therapy on various immunologic indices in patients with diffuse toxic goiter]. / Vliianie tireostaticheskoi terapii na nekotorye pokazateli immuniteta u bol'nykh diffuznym toksicheskim zobom.

The influence of thyrostatic therapy upon immunoglobulin A, M and G serum concentrations and lymphocytic blast-cell transformation in thyroglobulin and PHA presence in patients with diffuse toxic goiter was studied. The results of the immunological test used do not define quite accurately changes in clinical manifestations of the disease. In the majority of patients disorders of the humoral and/or cell immunity persist during the thyrotoxicosis compensatory stage. A tendency towards normalization or normalization of the parameters studied of T- and B-immune systems is seen under the action of thyrostatic therapy.

[Insulin and proinsulin degradation normally and in experimental diabetes]. / Degradatsiia insulina in proinsulina v norme i pri éksperimental'nom diabete.

The authors studied insulin and proinsulin degradation with homogenates of various rat tissues under normal conditions and in alloxan diabetes. The radioimmunological method was used for insulin determination by the decline of immunoreactive insulin and proinsulin from the reaction medium. Homogenates of various normal rat tissues are distributed by their capacity to destroy insulin and proinsulin in the order of decline as follows: the liver, kidneys, muscles, and the epididymal fat. In insulin equimolar quantities proinsulin was destroyed much less than insulin under the same experimental conditions. Alloxan diabetes led to reduction of the capacity of all the tissues homogenates to destroy both insulin and proinsulin. Reduction of degradation was the most pronounced when the muscle and adipose tissue homogenates were used.

[Clinical characteristics of selectivity of proteinuria in patients with diabetes mellitus]. / Klinicheskaia kharakteristika selektivnosti proteinurii u bol'nykh sakharnym diabetom.

A study was made of 43 patients suffering from diabetes mellitus using the method of proteinuria selectivity on polyacrylamide gel. Two types of proteinuria were distinguished: the first type repeated the electrophoregram of the plasma proteins completely or partially, the second type--the selective one--was characterized by excretion of individual plasma proteins. Diagnostic and prognostic value of the method of proteinuria selectivity is discussed.