[The vitamin D endocrine system and bone tissue mineral metabolism in rats with adjuvant arthritis: the effect of 1,25-dihydroxyvitamin D3]. / Endokrinnaia sistema vitamina D i mineral'nyi obmen kostnoi tkani u krys s ad''iuvantnym artritom: vliianie 1,25-digidroksivitamina D3.

Adjuvant arthritis was induced in male rats by injecting bacillus Calmette-Guèrin in mineral oil in a hindpaw. A decrease in bone density, calcium and phosphorus content due to polyarthritis was found in the tibia of the noninjected hind leg. Arthritic rats demonstrated serum 1,25-dihydroxyvitamin D deficiency along with constant level of 25-hydroxyvitamin D. The disease caused a significant expression of 1,25-dihydroxyvitamin D3 receptors in lymphocytes. Arthritic rats were treated with 1,25-dihydroxyvitamin D3 (0.15 mg/kg/day orally) for 35 days. The treatment prevented the development of osteoporosis and a decrease of 1,25-dihydroxyvitamin D levels as well as reduced the expression of 1,25-dihydroxyvitamin D receptors in lymphocytes.

[Effect of 1,25-dihydroxycholecalciferol and 24,25-dihydroxycholecalciferol on calcium homeostasis in rats treated with hydrocortisone]. / Vliianie 1,25-dioksikholekal'tsiferola i 24,25-dioksikholekal'tsiferola na gomeostaz kal'tsiia u krys, poluchaiushchikh gidrokortizon.

Physiological dose of 1,25(OH)2D3 (0.03 microgram) normalized the phosphorus-calcium metabolism and improved the state of bone tissue in rats treated with hydrocortisone. An increased dose of 1,25(OH)2D3 (0.15 microgram) caused hyperphosphatemia and augmented osteoporotic alterations in the hydrocortisone-treated animals. 24,25(OH)2D3 at a dose of 0.3 mg did not exhibit any positive effect on phosphorus-calcium metabolism and on the state of bone tissue in rats with exogenous hypercorticoidism. At the same time, high doses of 24,25(OH)2D3 increased distinctly the bone tissue density as well as the content of calcium and phosphorus. The most favourable state of the calcium homeostasis and of bone tissue in exogenous hypercorticoidism was observed after simultaneous administration of 1,25(OH)2D3 and 24,25(OH)2D3. These data suggest that a set functionally active metabolites of vitamin D3 should be used in cases of long-term treatment with glucocorticoids.

[Effect of 1,25-dioxycholecalciferol and 24,25-dioxycholecalciferol on calcium homeostasis in rats given hydrocortisone in the diet with various phosphorus contents]. / Vliianie 1,25-dioksikholekal'tsiferola i 24,25-dioksikholekal'tsiferola na gomeostaz kal'tsiia u krys poluchaiushchikh gidrokortizon na fone ratsiona s razlichnym soderzhaniem fosfora.

High content of phosphorus in the diet (1.8% of phosphorus in the diet, Ca:P ratio 1:3) accelerated the development of hypocalcemia and osteoporosis and increased their degree in rats which received hydrocortisone (3.5 mg/10 g bw a day for 4 weeks). Reduction of phosphorus consumption to 0.3% (Ca:P ration 1:0.5) essentially retarded the development of these disturbances and lowered their degree. The use of 1,25-dioxycholecalciferol and 24,25-dioxycholecalciferol in doses of 0.03 and 1.5 mg, respectively promoted the normalization of phosphorus-calcium metabolism and improvement of the status of the osseous tissue in rats given hydrocortisone coupled with both diets. The most beneficial affect on calcium homeostasis in exogenous hypercorticoidism was attained with the use of active metabolites of vitamin D3 coupled with the diet with a low phosphorus content (0.3%). In this case there was a complete normalization of the density of the osseous tissue and of the calcium and phosphorus content. In view of this fact it is advisable to combine active metabolites of vitamin D3 and the diet with a low phosphorus content.

[Comparative study of the effects of alpha-25-dihydroxycholecalciferol and 24, 25-dihydroxycholecalciferol on calcium-phosphorus metabolism and on bone tissue in experimental kidney insufficiency in rats]. / Sravnitel'noe izuchenie vliianiia lal'fa, 25-dioksikholekal'tsiferola i 24, 25-dioksikholekal'tsiferola na fosforno-kal'tsievyi obmen i kostnuiu tkan' pri éksperimental'noi pochechnoi nedostatochnosti u krys.

Experimental chronic kidney insufficiency (CKI; within 2-6 months) in rats, kept on a diet containing 0.6% Ca2+ and 0.6% P was accompanied by distinct azotemia, hyperphosphatemia, by a decrease in specific weight, in content of Ca2+, P and hydroxyproline in diaphyses as well as by a decrease in epiphyseal Ca2+. Daily administration of 0.025 micrograms of 1 alpha, 25-dihydroxy-cholecalciferol (1,25 (OH)2D3) into the animals did not normalize any of the patterns studied. At the same time, 1,25 (OH)2D3 increased the rate of hypercalciemia and demineralization of epiphyses, causing a slight hypercalciemia and increasing distinctly calcinosis of aorta as well as of the remaining part of the kidney. After daily administration of 24, 25-dihydroxycholecalciferol (24, 25 (OH)2D3) at a dose of 0.25 micrograms most of the patterns studied were normalized; specific weight, content of Ca2+ and P were increased in diaphyses simultaneously with a decrease in blood phosphorus concentration and in the level of azotemia. 24, 25 (OH)2D3 increased also the collagen content in diaphyses and epiphyses. The higher dose of 24, 25 (OH)2D3 (1.25 micrograms) did not exhibit higher effectivity. No one of the 24, 25 (OH)2D3 doses used did cause hypercalciemia and calcinosis. Combination of 0.025 micrograms 1,25 (OH)2D3 with 1.25 micrograms of 24, 25 (OH)2D3 decreased slightly the hypercalciemic, hyperphosphatemic and calcinosis inducing effects of 1,25 (OH)2D3 preventing completely the osteoporotic alterations in diaphyses but increasing the epiphysis demineralization; these results indicate that the doses of these metabolites must be decreased if their combination is required. The data obtained suggest that 24, 25 (OH)2D3 is a more effective and safe drug in correction of Ca2+-P metabolism impairments as well as of bone destruction under kidney insufficiency conditions as compared with 1,25 (OH)2D3.

[Role of sterols in the interaction of polyene antibiotics with lipid membranes]. / Rol' sterinov vo vzaimodeistvii polienovykh antibiotikov s lipidnymi membranami.

The problem whether the membrane sterols are indirect acceptors of polyenic antibiotics or they play the role of substances providing conditions (at the expense of putting in order the membrane phospholipids) for formation of conductive complexes (ionic canals) from the antibiotic molecules is discussed. The comparative study on the ability of sterols of various structure (ergosterol, 7-dehydrocholesterol, cholesterol, 5 alpha-cholestan-3 beta-ol) to interact with the membrane phospholipids and to increase the sensitivity of such membranes to amphotericin B showed no correlation between the levels of these properties. The value of the changes in the cross elasticity module (E) of artificial bilayer lipid membranes from egg lecithin on introduction of the above sterols into their composition was used as the criterion for the interaction level. The absence of correlation between the above properties of the sterols indicated that the role of the sterols in interaction of polyenic antibiotics with the membranes could not be considered as the only effect of the sterols on putting in order the phospholipids, which confirmed the hypothesis on the acceptor function of the sterols with respect to polyenic antibiotics. The study of the effect of amphotericin B on the elastic properties of the cholesterol-containing bilayer membranes isolated from egg lecithin showed tha the values of the longitudinal and cross elasticity modules of the membranes did not change during introduction into the membranes of the ionic canals.

[Comparative study of the biological activity and toxic effect of 1alpha-hydroxycholecalciferol and ergocalciferol in rats]. / Sravnitel'noe izuchenie biologicheskoi aktivnosti i toksicheskogo deistviia 1alpha-oksikholekal'tsiferola i érgokal'tsiferola na krysakh.

Single administration of 0.25 microgram of sunthetic Ialpha-hydroxycholecalciferol (IalphaOHD3) into nephrectomized rats, maintained at D-avitaminous diet, improved the active transport of calcium ions against the concentration gradient in small intestine of these animals, whereas ergocalciferol was biologically inactive under the same conditions. Administration of IalphaOHD3 during 5 days at a dose 0.025 microgram normalized calcium content in blood serum of rats with D-avitaminosis, Increased doses of IalphaOHD3, administered into intact animals, caused transient hyperphosphatemia, hypercalcemia, calcinosis of internal tissues (kidney heart, aorta) as well as death of some animals. IalphaOHD3 exceeded 400-fold the hypercalcemic and calcinose effects of ergocalciferol. LD50 for IalphaOHD3 was equal to 100 microgram/kg, if it was administered during 5 days per os. Tissue calcinosis was developed after administration of a daily dose 10 microgram/kg, moderate hypercalcemia was caused by a daily dose 1 microgram/kg or 0.25 microgram per an animal; this amount is only 10-fold higher as compared with the physiologic requirement. Ergocalciferol caused hypercalcemia and metastatic calcification only at a dose 4000 microgram/kg. Clinical use of IalphaOHD3 at doses, exceeding the physiologic requirements, has to be prohibited due to high activity of the preparation and to toxicity of its increased doses.

[1 alpha-hydroxyvitamin D3: chemical synthesis and biological effect]. / 1 alpha-oksivitamin D3: khimicheskii sintez i biologicheskoe deistvie.

A method for the synthesis of an analog of vitamin D3--1alpha-hydroxy vitamin D3 (1alpha-OH D3) from cholesta-4,6-dien-3beta-ol was developed. Biological activity of this compound in the chick organism was measured. The growth stimulating effect of 1alpha-OH D3 and its effect on bone tissue mineralization and serum biochemical parameters (content of calcium, inorganic phosphorus and activity of alkaline phosphatase) were 4--5 times higher than those of vitamin D3 in low doses (19.5--39 pmole/day). In chicks given 1alpha-OH D3 at doses of 39--195 pmole/day most biochemical parameters reached plateau typical of chicks adequately provided with vitamin D. A peculiar feature of 1alpha-OH D3 was a rapid response of the chick organism to/low doses. As early as one hour after intramuscular injection of 650 pmole of 1alpha-OH D3 to D-avitaminotic chicks, the content of calcium-bound protein in the intestinal mucosa and active transport of calcium ions in the inverted intestinal sac increased drastically. It was demonstrated that 1alpha-OH D3 showed antirachitic action, when the physiological reaction to vitamin D3 was inhibited by dietary strontium.