[Significance of estradiol in the development of fibrosis in systemic scleroderma (bases of sexual predisposition to the disease)]. / Znachenie éstradiola v razvitii fibroza pri sistemnoi sklerodermii (osnovy polovoi predraspolozhennosti k zabolevaniiu).

The influence of estradiol (E2) was studied on the production of type III procollagen by cultivated fibroblasts from the skin of healthy donors and SSD patients. It has been found that when in the norm E2 (concentration 10(-8) and 10(-7) M) inhibits the production of type III procollagen. In SSD the hormone's effect is not found. Here the quantity of E2 receptors in cells from SSD patients is 1.96 time lower than the norm. The resulted data testify to the fact that the decrease of E2 receptors in fibroblasts from SSD patients may be one of the factors contributing to the increase in the functional activity of cells and to the fibrosis progression.

[The effect of cyclic nucleotides on the specific binding of estradiol by skin fibroblasts in the normal state and in systemic scleroderma]. / Vliianie tsiklicheskikh nukleotidov na spetsificheskoe sviazyvanie éstradiola fibroblastami kozhi v norme i pri sistemnoi sklerodermii.

Specific binding of estradiol E2 was studied in homogenates of cultivated skin fibroblasts from healthy persons and patients with systemic sclerodermia as well as effect of cAMP and cGMP on the hormone binding was evaluated. Binding of estradiol E2 was decreased 4-fold in systemic sclerodermia. cAMP and cGMP were of importance in activation of the estradiol specific binding. Under conditions of normal state cAMP 10(-6) elevated 2-fold the estradiol specific binding, while the stimulation was not observed in systemic sclerodermia. However, cGMP 10(-6) M did not affect distinctly the estradiol E2 binding by fibroblasts of healthy volunteers but stimulated the hormone binding in systemic sclerodermia as a result of which the binding values were increased practically up to the basal level of normal state.

Cyclic nucleotides and calcium transport in cultured dermal fibroblasts from progressive systemic sclerosis and rheumatoid arthritis patients.

Levels of cAMP were decreased and cGMP increased in progressive systemic sclerosis (PSS) fibroblasts compared with normal fibroblasts. PSS cells took up unusually large quantities of Ca++. The epinephrine-induced increases in cAMP were diminished sixfold and epinephrine-induced Ca++ uptake was abnormal in PSS cells. Considerable heterogeneity was observed in rheumatoid arthritis fibroblasts. Membrane-bound abnormalities in (PSS) cells may be of importance in the defective control of collagen production in progressive systemic sclerosis.

[Mechanism of disruption in the metabolism of the cyclic AMP system in myocardial tissue in allergic deterioration]. / K mekhanizmu narushenii v sisteme obmena tsiklicheskogo AMP v tkani miokarda pri ego allergicheskom povrezhdenii.

Role of hormones, guanylic nucleotides and sodium fluoride in regulation of adenylate cyclase activity was studied in rabbit heart under conditions of its allergic deterioration caused by repeated administration of horse blood serum. In the allergic injury activation of adenylate cyclase was found to occur simultaneously with a decrease in the rate of the enzyme stimulation by means of either the hormones in presence of guanylic nucleotides or by sodium fluoride. Without guanylic nucleotides the hormones did not stimulate adenylate cyclase activity. At the same time, under conditions of allergic sensitization the hormone stimulated adenylate cyclase was practically not activated by guanylic nucleotides. Unspecific desensitization of membrane receptors to hormones was responsible for impairments in regulation of adenylate cyclase activity under conditions of allergic sensitization. In the allergy the functional activity of N-protein was not altered, whereas its coupling with the catalytic component was impaired by sodium fluoride.

[Effect of isoproterenol on collagen synthesis in cultured skin fibroblasts in patients with systemic scleroderma]. / Effekt izoproterenola na sintez kollagena v kul'turakh fibroblastov kozhi bol'nykh sistemnoi sklerodermiei.

Production of collagen and intracellular content of 3,5'-cAMP were studied after treatment with isoproterenol of fibroblast cultures of II-XI passages obtained from healthy donors and from patients with systemic scleroderma. Incubation of control fibroblasts with isoproterenol within 6 hrs caused an increase in the cell cAMP concentration by 260-385% and inhibited the collagen synthesis by 27-58%. Distinct correlation (r = -0.951) was found in fibroblasts of the patients with sclerodermia between the capacity of the cells to accumulate cAMP in presence of isoproterenol and their ability to produce collagen. The inhibitory effect of isoproterenol on collagen synthesis was not found in the cells with initially increased collagen-producing activity, but the effect was maintained in the strains with the decreased rate of collagen synthesis. The data obtained suggest that impairments in beta-adrenergic functions and the decrease in cAMP concentration in fibroblasts may be responsible for the elevated rate of collagen synthesis in the patients with systemic sclerodermia.

[Transport of calcium ions and content of cyclic nucleotides in fibroblast cultures from skin of patients with rheumatoid arthritis]. / Transport ionov kal'tsiia i soderzhanie tsiklicheskikh nukleotidov v kul'turakh fibroblastov kozhi bol'nykh revmatoidnym artritom.

Content of cyclic nucleotides and the rate of Ca2+ transport into cells were studied in fibroblast cultures from skin of patients with rheumatoid arthritis within II-VI transfers during the stationary phase of growth. There were no differences as compared with controls. Effect of adrenaline on cAMP content was decreased as compared with the controls and the hormone influence on the rate of Ca2+ transport was dissimilar: in 5 patients out of the group of 13 persons--there was noted a stimulating effect (it was the case as in healthy persons), while in other patients the effect was either absent or adrenaline inhibited the Ca2+ transport. Similarly, in rheumatoid arthritis estradiol either did not affect the Ca2+ transport or its effect was opposite as compared with the normal state. The data obtained are discussed in comparison with the results on systemic sclerodermia published earlier.

[Effect of epinephrine on a culture of normal skin fibroblasts and fibroblasts in systemic scleroderma]. / Deistvie adrenalina na kul'turu fibroblastov kozhi v norme i pri sistemnoi sklerodermii.

Decrease in content of cAMP and increase--of cGMP as well as stimulation of Ca2+ transport into cells were found in cell cultures of skin fibroblasts from patients with systemic scleroderma (SSD) as compared with normal state. Adrenaline affected dissimilarly the fibroblasts from the patients and healthy donors. In SSD the stimulating effect of adrenaline (10(-7)M) on the cAMP content was decreased more than 6-fold as compared with normal state; at the same time, transport of Ca2+ was inhibited by the hormone (2 X 10(-6)M) in SSD contrary to a stimulating effect of adrenaline in normal cells. Blocking of beta-adrenoreceptors with inderal removed completely the effect of adrenaline on Ca2+ transport both in normal and pathological states. Alteration in the reactions of fibroblasts to catecholamines might be important in deterioration of the physiological mechanism including inhibition of collagen synthesis in SSD.

[Adenylate cyclase system and calcium transport in the cardiac muscle of normal rabbits and rabbits with allergic heart damage]. / Adenilattsiklaznaia sistema i transport kal'tsiia v serdechnoi myshtse krolikov v norme i pri allergicheskom povrezhdenii.

A 2,3-fold increase of cAMP concentration in rabbit myocardium, increase in basal activity of adenylate cyclase and inhibition of phosphodiesterase were found in allergic impairment of heart muscle in response to repeated administration of normal horse blood serum. In presence of adrenaline and NaF the rate of adenylate cyclase activation was distinctly decreased, indicating the "desensitization" of the enzyme. At the same time, parameters of Ca2+ transport were altered; the alterations were expressed as intensification of 45Ca turnover in mitochondria and in the fraction of sarcoplasmic reticulum, as well as distinct increase in the initial rate of Ca2+ penetration into mitochondria and increase in content of calcium in the organelles.

[Calcium ion uptake by the skin fibroblast culture under normal conditions and in systemic diseases of the connective tissue]. / Potreblenie ionov kal'tsiia kul'turoi fibroblastov kozhi v norme i pri sistemnykh porazheniiakh soedinitel'noi tkani.

Radioactive calcium (45Ca) uptake and the effect of adrenaline on this process was studied on the suspension of cells derived from the monolayer cultures of fibroblasts of the skin of healthy donors and of patients with systemic scleroderma and rheumatic fever. A significant increase of calcium uptake was shown in case of scleroderma in comparison with the normal and rheumatism cases. Adrenaline (2 X 10(-7)--2 X 10(-5) M) enhanced the rate of calcium uptake by fibroblasts in control and had the opposite effect in scleroderma. The data obtained indicated alteration of the fibroblast membrane function in systemic scleroderma which could underlay the change in the metabolic activity of these cells.

[Calcium transport in rabbit myocardial cells during experimental heart damage]. / Transport kal'tsiia v kletkakh miokarda krolikov pri éksperimental'nykh povrezhdeniiakh serdtsa.

Content and distribution of 45Ca, administered intravenously, were studied in fractions of rabbit myocardial tissue in experimental allergic and caused by injections of adrenaline heart impairments. Concentration of Ca was increased in mitochondria as well as its binding was stimulated both in mitochondria and in sarcoplasmic reticulum. Increased Ca utilization by mitichondria was also shown in vitro. Correlation between Ca accumulation in mitochondria and energy metabolism impairment in myocardium is discussed. The distinct increase of Ca concentration in mitochondria simultaneously with stabilization of its content in homogenate of myocardial tissue suggest that amount of Ca, bound to myofibrillar proteins, is decreased under the pathological conditions studied.

[Effect of allergic damage on plastic metabolism of the myocardium in rabbits]. / Vliianie allergicheskogo povrezhdeniia na plasticheskii obem miokarda krolikov

The plastic metabolism of the myocardium in rabbits was studied after varying periods of allergic damage induced by repeated injections of normal horse serum. An accelerated decompostion of the myofibril proteins was demomstrated to occur during the acute phase. During the reparation phase, an activation of the protein synthesis in the myocardium occurred. The newly synthesized myofibril proteins had a longer turnover in the tissues, than under normal conditions. The turnover time of the mitochondrial proteins did not differ from the normal one.

[Ultrastructure and plastic metabolism of the myocardium in allergic lesion of the heart]. / Ul'trastruktura i plasticheskii obmen miokarda pri allergicheskom povrezhdenii serdtsa

Allergic damage was induced in the hearts of senstized rabbits by way of slow intravenous injections of permissible doses of an antigen. One to 20 days after such a weakened anaphylactic reaction of the walls of the left auriculum were examined by light and electron microscopy. After one day, the histological studies revealed in all layers of the ventricle and auriculum oedematous and discirculatory manifestations, and electron microscopy demonstrated a complex of reversible sub-microscopic changes in the myocytes of the myocardium, their contractile organells being damaged predominantly. The biochemical studies permitted to reveal an activation of the decomposition of the myocardial myofibrillar proteins that was not accompanied by a proportional decomposition of the sarcoplasmic and connective-tissue proteins. The inner architecture of the myocytes was restored at the expense of the intracellular regenerative processes with transient hyperplasia of the intracellular regenerative processes with transient hyperplasia of the protein synthesizing organells of the myocytes.

[Half-life of rabbit heart mitochondria under normal conditions and in experimental allergic lesions of the heart]. / Period poluzhizni mitokhondrii serdtsa krolika v norme i pri éksperimental'nom allergicheskom povrezhdenii serdtsa

Half-life of mitochondrial proteins and cytochrome C of rabbit myocardium was determined with glycine-I-C14 and H3-5-aminolevulinic acid, respectively, as precursors. Half-life of mitochondrial proteins calculated from the curve of the gradual radioactivity decline was 14.4 days, and that of cytochrome C--11.8 days; reutilization of glycine-C14 in plastic metabolism did not exceed 20%. No difference from control was noticed in rabbits with an experimental allergic heart damage.