Effect of Sandimmun Neoral on the level of bivalent cations in erythrocytes of kidney transplant recipients.

In a 4 month study, a group of 16 patients with stable renal graft function receiving triple immunosuppressive therapy including cyclosporin A (Cy A) were investigated for the levels of calcium, magnesium and zinc in erythrocytes. The patients were randomized to be converted to the new microemulsion formulation (Sandimmun Neoral) in a 1:1 fashion (n = 8) or to continue with the classical formulation (Sandimmun) (n = 8). The concentrations of creatinine, phosphate, alkaline phosphatase activity, calcium, magnesium and zinc were measured twice a month in blood plasma. The concentration of calcium, magnesium and zinc in erythrocytes was also measured. The concentration of magnesium in blood plasma and erythrocytes during the study showed no deviation from normal values. The level of zinc in erythrocytes was almost twice as high as in normal healthy controls and was not dependent on Cy A formulation. Calcium content in erythrocytes of patients receiving Sandimmun was 27.6% higher than in healthy persons. Conversion of the patients to Sandimmun Neoral normalized the calcium concentration in erythrocytes and caused a transient increase of calcium levels in blood plasma.

[Effects of calcium on the course of strontium toxicosis]. / Vliianie kal'tsiia na techenie strontsievogo toksikoza.

Chronic intake of Sr for 20 days by chickens caused in them a delay in body mass increase and symptoms of rickets in spite of complete provision with vitamin D. There were low levels of Ca, P, enhanced activity of alkaline phosphatase in the serum, inhibited mineralization of bone tissue, reduced levels of vitamin D-dependent calcium-binding protein, Sr accumulation in various tissues. Enrichment with Ca of the chickens ration diminished the above signs of Sr toxicosis. It is suggested that a protective effect of Ca in chronic Sr toxicity may be due to more active discrimination of Sr against Ca in intestinal assimilation of these cations.

[24,25-Dihydroxyvitamin D3 modulates the effect of 1alpha-hydroxyvitamin D3 on B lymphocyte maturation in chickens]. / 24,25-Digidroksivitamin D3 moduliruet deistvie 1alpha-gidroksivitamina D3 na sozrevanie B-limfotsitov u tsipliat.

Patterns of calcium metabolism and maturation of lymphocytes in chicken Fabricius bursa were studied in presence of various doses of I alpha-hydroxy vitamin D3 and 24,25-dihydroxy vitamin D3 administered separately and at various combinations. 24,25(OH2)D3 was distinctly less effective in the antirickets activity as compared with I alpha (OH)D3. A decrease in mass of Fabricius bursa and inhibition of lymphocytes maturation within early steps were observed in the birds with rickets. A toxic dose of I alpha (OH)D3 caused pseudohypertrophy of Fabricius bursa. Small doses of these drugs administered simultaneously exhibited higher effect both on rickets and on stimulation of B lymphocytes maturation. 24,25(OH)2D3 attenuated the negative effect of either subtoxic (0.65 nmol/day) or toxic (1.3 nmol/day) doses of I alpha (OH)D3 on an increase in body mass, calcemia, ash content of bones, content of small lymphocytes in Fabricius bursa.

[Effect of strontium on the anti-rickets activity of vitamin D3 and its hydroxy analogs]. / Deistvie strontsiia na antirakhiticheskuiu aktivnost' vitamina D3 i ego gidroksilirovannykh analogov.

Antirickets activity of vitamin D3 and of its derivatives 1 alpha- and 25-hydroxy vitamin D3 1.25- and 24,25-dihydroxy vitamin D3 and 1,24,25-trihydroxy vitamin D3 was studied in chicken maintained on a diet containing various amount (0.01-2.40 mg) of strontium. Vitamin D3 as well as its 24-hydroxy and 24,25-dihydroxy derivatives lost their antirickets activity in presence of high strontium concentrations. Under the same conditions I alpha-hydroxy, 1,25-dihydroxy and 1,24,25-trihydroxy vitamins D3 retained the ability both to induce calcium-binding protein synthesis in intestinal epithelium and to stimulate bone tissue mineralization, although to a lesser degree as compared with controls, kept on strontium-free diet. These results suggest that presence of I alpha-OH-group in the steroid molecule is necessary for expression of maximal biological activity under conditions of elevated strontium content in diet while the activity of hydroxylase is inhibited in kidney. At the same time, the vitamin D3 derivatives containing the OH-group are responsible for impairments caused by increased accumulation of strontium.

[Evaluation of the vitamin D activity of yeasts with altered sterol metabolism]. / Otsenka D-vitaminnoi aktivnosti shtammov drozhzhei s izmenennym metabolizmom sterinov.

The sterol content of Saccharomyces strains with altered ergosterol metabolism was studied by UV-spectrophotometry, thin-layer chromatography and chromatographic mass-spectroscopy. A technique for estimation of D-vitamin activity of the yeast strains is proposed. The irradiated biomass of the strains accumulated ergosta-5,7-dien-3 beta-ol and also cholesta-5,7,24-trien-3 beta-ol and cholesta-5,7,22,24-tetraen-3 beta-ol is characterized by high antirachitic activity.

[Effect of vitamin D on inorganic phosphorus transport and alkaline phosphatase activity of the small intestine of chickens]. / Deistvie vitamina D na transport neorganicheskogo fosfora i aktivnost' shchelochnoi fosfapazy v tonkoi kishke tsypliat.

Effect of vitamin D on the intensity of inorganic phosphorus absorption and the activity of unspecific alkaline phosphatase in the shick small intestine was studied in vitro on everted gut sacks. Repletion of rachitic chicks with vitamin D3 (500 IU) 72 hrs prior to decapitation enhanced the transport rate 3.5-fold. Concomitantly, the activity of alkaline phosphatase increased 1.8-fold. Analysis of the data obtained shows the important role that the interaction of alkaline phosphatase and inorganic phosphorus transport plays in phosphorus absorption from sources of organic nature.

Absence of alkaline phosphatase-linked inorganic phosphate transport in the chick jejunum.

The role of non-specific alkaline phosphatase-linked inorganic phosphate (Pi) transport in the chick jejunum was investigated by using the everted gut sac technique. The highest intensity of transport was observed for free Pi. The maximal transport rate was considerably reduced when beta-glycerophosphate was used as a single source of phosphorus. These results suggested absence of the alkaline phosphatase-linked transport system for inorganic phosphate in the epithelium of the chick jejunum. Studies of Mg effect on Pi absorption as well as examination of temporal changes in Pi transport rate and beta-glycerophosphate hydrolysis rate by intestinal brush border alkaline phosphatase gave further backing to this suggestion.

Vitamin D3 and 1,25-dihydroxyvitamin D3 stimulate the skeletal muscle-calcium mobilization in rachitic chicks.

The Ca content in skeletal muscle relative to vitamin D3 intake was studied in chicks. It was found that the Ca content in rachitic chick muscle was significantly higher than normal and it decreased with vitamin D3 treatment. In 4-week-old chicks fed a vitamin D-deficient diet, the Ca content in leg muscle reached 9.86 +/- 1.07 mg/100 g wet wt, although in chicks receiving vitamin D3 in doses of 100 and 500 IU/kg diet, it was 7.80 +/- 0.72 and 6.08 +/- 0.61 mg/100 g wet wt, respectively. A single i.m. dose of 0.50 micrograms of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) or vitamin D3 caused a dramatic decrease in the muscle Ca content by 3 to 6 h after the injection. A simultaneous rise in the Ca level in blood serum was observed. However, at this time the Ca binding protein content in duodenal mucosa and the stimulation of Ca absorption were negligible. These findings allow the conclusion that the vitamin D deficiency in chicks leads to a surplus Ca accumulation in skeletal muscle. The administration of vitamin D3 or its metabolites causes rapid Ca release during the first 6 h. This may be the source of the Ca level increase in blood serum. In this respect 1,25(OH)2D3 was much more effective than vitamin D3.

[Comparative antirachitic activity of 1,25-dihydroxyvitamin D3 and 1 alpha-hydroxyvitamin D3 in the chick]. / Sravnenie antirakhiticheskoi aktivnosti 1,25-dioksivitamina D3 i 1 alpha-oksivitamina D3 u tsypliat.

1,25-dihydroxy vitamin D3 and its synthetic analogue 1 alpha-hydroxy vitamin D3 were administered into chicken at the doses of 0.025, 0.05 and 0.1 micrograms per day within 25 days. Effect of the vitamins was estimated by a net gain of biomass, by biochemical alterations in blood, synthesis of calcium-binding protein, relative mass of parathyroid glands and by content of inorganic residue in bone tissue. Both vitamin preparations exhibited similar antirickety activity.

[Comparative antirachitic activity of vitamins D2 and D3 in the body of chicks]. / Sravnitel'naia antirakhiticheskaia aktivnost' vitaminov D2 i D3 v organizme tsypliat.

In the four-week study the antirachitic action of vitamin D2 in different does (5000, 7500, 10 000 I. U. per kg food) and of vitamin D3 in a dose of 500 I. U. per kg food was investigated in chicks. The vitamin efficiency was measured with respect to the following seven parameters: weight gain, serum content of Ca and P, serum activity of alkaline phosphatase, bone ash content, content of Ca-binding protein in the duodenal mucosa, and weight of parathyroid glands. In regard to these parameters, vitamin D2 in a dose of 7500 I. U./kg and vitamin D3 in a dose of 500 I.U./kg produced a similar effect. Thus, the antirachitic effect of vitamin D3 was 15 times higher than that of vitamin D2. In the three-day study of the effect of vitamins D2 and D3 on the synthesis of Ca-binding protein it was found that they exerted a similar effect when the dose of vitamin D2 was 14.5 times higher than that of vitamin D3.

[Direct stimulatory action of blood serum, vitamin D3, and its hydroxy-analogs on calcium transport in the small intestine of chicks in vitro]. / Priamoe stimuliruiushchee deistvie syvorotki krovi, vitamina D3 i ego oksi-analogov an transport kal'tsiia v tonkoi kishke tsypliat in vitro.

A study was made of the effect of blood serum, vitamin D3 and its hydroxy-analogs (25-hydroxyvitamin D4. 1 alpha-hydroxyvitamin D3) on Ca2+ transport across the wall of the noninverted small sac of D-avitaminosis chicken during incubation in vitro. It was shown that blood serum from chickens fed vitamin D3 in different doses (50--20 000 IU) and at varying time (1--72 h) before sacrifice produced a marked stimulating action on the cation transport 10 min after administration into the intestinal cavity as compared with the effect produced by the serum from D-avitaminosis chickens. Administration into the intestine of vitamin D3 or its hydroxy-analogs in physiological doses (6.25--25.0 ng) also significantly stimulated Ca+ transport over 10 min of incubation.

Reversal of prednisolone-induced inhibition of intestinal calcium-binding protein synthesis by 1 alpha-hydroxycholecalciferol in chicks.

Effects of prednisolone on the biochemical indices of blood serum, ash content in bones, calcium absorption and calcium-binding protein (CaBP) in the intestinal mucosa were studied. The oral administration of prednisolone (10 mg/kg) for 2 weeks reduced CaBP content and calcium absorption to the level typical for D-avitaminosis. The oral administration of 1 alpha-hydroxycholecalciferol (390 pmoles/day) in combination with prednisolone for a week returned calcium absorption and CaBP to the control value.

[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.

[Biological method of quantitating vitamin D in different preparations and diets]. / Biologicheskii metod kolichestvennogo opredeleniia bitamina D v razlichnykh preparatakh i kormakh.

A biological method for quantitative assay of vitamin D3 in various preparations has been developed. The method is based on a close correlation between the vitamin D3 dose and the content of calcium-binding protein in the duodenal mucosa of rachitic chickens 72 hrs after vitamin D3 administration. Calcium-binding protein is assayed by radial immunodiffusion in agar-agar. The calibration curve of the dose-protein dependence allows measurements of I to 500 IU of vitamin D3 in the sample tested. The method shows good accuracy and reproducibility. The paper presents the results of quantitation of vitamin D in various preparations.