Evaluation of Cellular Toxicity and Preclinical Safety of Using an Inhalable Liposomal form of Dexamethasone.

A liposomal form of dexamethasone was obtained. Liposomal vesicles were formed. The efficiency of incorporating dexamethasone into the liposomes was 99.7%. The cytotoxicity of the obtained liposomes was studied on a culture of human lung fibroblast cells using the MTT assay. The toxicity of liposomal dexamethasone was less than that of dexamethasone solution after a 24-h incubation. The half-maximum inhibitory concentration (IC50) was not achieved after 24 h when exposed to liposomal dexamethasone whereas IC50 was 27.5 mg/mL for lecithin (empty liposomes) and 177 µg/mL for dexamethasone solution. The toxicity of liposomal dexamethasone increased much more than that of dexamethasone solution after 48 h of incubation with IC50 values of 36 and 156 µg/mL, respectively. Thus, the liposomal form of dexamethasone has a latent period for implementation of the cytostatic (antiproliferative) action. Experiments on laboratory white rats of both sexes revealed that the inhalation use of liposomal dexamethasone insignificantly changed the functional parameters of their respiratory and cardiovascular systems. The study results could be used for conducting clinical trials.

Design of Nanosomal Form of Aprotinin.

Liposomes containing aprotinin were produced by the phase inversion technique and purified by gel filtration. Aprotinin inclusion was assessed fluorescence labeling of the protein. The size of obtained liposomes was 212±35 nm and aprotinin concentration in the liposomal suspension was 3000 KIU/ml. The efficiency of aprotinin inclusion into liposomes was 31.9%.

[Effect of decompression on the compliment system]. / Vliianie dekompressii na sostoianie sistemy komplementa.

Decompression effects on the complement system were studied in healthy male volunteers who made 39 "ascents" to 7000-9000 m and 13 "descents" to 30 m. Hemolytic activity of the complement system components was determined in the blood serum taken from the cubital vein of the subjects immediately before and after decompression. The results of this study showed that in the absence symptoms of decompression sickness (DCS) and doppler-detected gas bubbles (GB) the subjects reduced activities of C1 and C4. In the event of altitude joint pains the activity of the complement system components was significantly unchanged. In subjects with circulating GB the complement status was more markedly altered following simulated descents rather than ascents pointing to an alternative activation of the system. Subject with the skin DCS had a two-fold reduction of the complement system activity by the alternative mechanism and a reduction of C5 activity whereas there were no changes in the activities of C1, C2, C3, C4, CH50. It is concluded that alternative activation of the complement system may be involved in the genesis of those DCS forms whose emergence relates to gaseous embolism of veins and pulmonary capillaries.

[Change of the complement level in patients with insulin-dependent diabetes mellitus in the course of intensified insulin therapy]. / Izmenenie urovnia komplementa u bol'nykh insulinzavisimym sakharnym diabetom pri intensifitsirovannoi insulinoterapii.

Intensified insulin therapy in patients with type I diabetes mellitus is accompanied by a decrease in a total daily dose of insulin and the activity of the first 5 components of the classical pathway and CH50. A decrease in function of the first 5 components of the complement against a background of intensified insulin therapy can serve as a positive prognostic criterion of stabilization of development of diabetic angiopathies.

[Insulin-dependent complement activity in the serum of patients with diabetes mellitus]. / Insulinz visimaia aktivnost' komplementa v syvorotke bol'nykh sakharnym diabetom.

Complement system was comparatively evaluated in 68 patients with diabetes mellitus and 104 healthy subjects. Hemolytic activity was examined for components C1, C2, C3, C4 and C5, and overall activity of the classic pathways was defined. The complement status appeared different for men and women. Females demonstrated hypofunction of the majority of the complement components, subcompensation in the absence of angiopathies, in decompensation complicated by angiopathies the activity was enhanced. In uneventful course of diabetes mellitus in males component C4 was activated remaining above normal though reduced in decompensation with angiopathies. High complement level in females could serve an aggravating factor, it depends on the dose of exogenic insulin.

[Analysis of the composition of the microelements in the hair of normal subjects and in disseminated sclerosis]. / Analiz sostava mikroélementov volos v norme i pri rasseiannom skleroze.

The modification of analysis of the hair trace elements involves hair dissolution in nitric acid and analysis of the iron, manganese, and copper by flameless atomic-absorption spectrometry and of zinc by the flame technique. Trace element content has been measured in the hair of 26 normal subjects aged 20-50 and of 20 children. In adults iron, manganese, zinc, and copper concentrations were 12.2 +/- 0.6, 0.55 +/- 0.11, 172 +/- 8, and 12.8 +/- 0.6 micrograms/g, respectively. Higher concentrations of manganese have been observed in females, as well as a tendency to an increase of zinc levels in adults. Analysis of copper in the hair of 44 patients with disseminated sclerosis, carried out by the suggested technique and by direct analysis of the solid sample in a graphite cuvette, has revealed a trend to an elevation of copper content vs. the norm. No significant differences between the hair manganese levels of females and males have been revealed in the patients, such differences being typical of normal subjects. Fluctuations in copper concentrations at different sites of a single hair and a strand have been analyzed in the patients and in normal subjects.