Characterization of SNF472 pharmacokinetics and efficacy in uremic and non-uremic rats models of cardiovascular calcification.

End-stage renal disease is strongly associated with progressive cardiovascular calcification (CVC) and there is currently no therapy targeted to treat CVC. SNF472 is an experimental formulation under development for treatment of soft tissue calcification. We have investigated the pharmacokinetics of SNF472 administration in rats and its inhibitory effects on CVC. SNF472 was studied in three rat models: (1) prevention of vitamin D3-induced CVC with an intravenous SNF472 bolus of 1 mg/kg SNF472, (2) inhibition of progression of vitamin D3-induced CVC with a subcutaneous SNF472 bolus of 10 or 60 mg/kg SNF472, starting after calcification induction, (3) CVC in adenine-induced uremic rats treated with 50 mg/kg SNF472 via i.v. 4h -infusion. Uremic rats presented lower plasma levels of SNF472 than control animals after i.v. infusion. CVC in non-uremic rats was inhibited by 60-70% after treatment with SNF472 and progression of cardiac calcification completely blocked. Development of CVC in uremic rats was inhibited by up to 80% following i.v. infusion of SNF472. SNF472 inhibits the development and progression of CVC in uremic and non-uremic rats in the same range of SNF472 plasma levels but using in each case the required dose to obtain those levels. These results collectively support the development of SNF472 as a novel therapeutic option for treatment of CVC in humans.

[Fatty liver in elderly patients with atherosclerotic coronary artery disease (according to autopsy data)].

In article it is a question of morphological research of fragments of tissue of a liver at 143 elderly and old patients with atherosclerosis of the coronary arteries which have died on offices of the S-Petersburg hospital for veterans of wars in 2006-2010. Average age of the died patients was defined in the range from 61 till 98 years and made 82.3 ± 1.3 years. It is established that at geriatric patients with atherosclerotic defeat of coronary arteries fatty regeneration of a liver was observed in 25.9 ± 7.3%; more than at 2\3 geriatric patients with atherosclerosis of coronary arteries it was noted cteatogpatit with the minimum degree of the activity, thus specified degree of activity came to light at the surveyed patients with fatty regeneration of a liver (77.8 ± 8.0% against 60.7 ± 6.1% in group without fatty regeneration of a liver) more often. Cardiovascular diseases caused death of patients with atherosclerosis of coronary arteries and fatty regeneration of a liver, than in group of patients without a fatty degeneration of a liver (91.7 ± 4.8% of cases and 73.8 ± 4.9% of cases respectively) more often. Patients of senile age with atherosclerosis of coronary arteries and fatty regeneration of a liver died because of cardiovascular diseases, than their contemporaries in group without fatty regeneration of a liver (89.7 ± 6.1% and 71.3 ± 5.7% respectively) more often.

[Frequency of some diseases and conditions in geriatric patients with coronary heart disease and various genotypes of transcription factor 7-like 2 protein].

In 2009-2010, 98 patients diagnosed with the coronary heart disease, but without the expressed metabolic violations, decompensated conditions and diseases were surveyed. Patients of 60-90 years were divided by age into two groups: younger than 75 years--47 people; 75 years and older--51; there were 41 women and 57 men; the ratio between women and men was 1:1.4; average age was 76.0 ± 1.3 years. The average age of women was 76.0 ± 1.8 years, men--76.1 ± 2,0 years. 96.0 ± 2.0% of geriatric patients with CHD complained of steno-cardiac pains in pre-cardiac area; the excess mass of a body was observed in 43.4 ± 5.0% of geriatric patients with CHD, acute myocardial infarction in the anamnesis was noted in 52.5 ± 6.9% (n = 52); hypertensive illness had 98.0 ± 1.4% (n = 97). Patients had the favorable average levels of lipoproteins of high density (not lower than 1 mmol/l). A significant number (79.2 ± 5.6%) of patients had hemodynamically significant narrowing of coronary vessels (75% and more), while the area of myocardial hypokinesia was observed in 41.2 ± 6.9% of patients, sharp violation of brain blood circulation was noted in 14.1 ± 9.8%. Wild type homozygous genotype of TCF7L2 gene was detected significantly more often (77.6 ± 4.7%) in patients of advanced and senile age with CHD, regardless of age group, exis-tence of accompanying diseases and conditions, such as previous myocardial damage, acute disorders of cerebral circulation and fatty degeneration of the liver. However allele of risk T (totally C/Tand T/T) of TCF7L2 gene came to light in 22.4 ± 9.1% of geriatric patients with CHD, that contributes to development of a metabolic syndrome in such patients and reduces term of their life.

[Genotype and allele frequencies of UCP and PPAR gene families in residents of besieged Leningrad and in the control group].

Genotype and allele frequencies of uncoupling proteins 2 and 3 genes (UCP2 and UCP3) and peroxisome proliferator-activated receptors genes (PPARA, PPARD and PPARG) were studied in 206 residents of the siege and in 139 individuals of more than 69 years old (control group). Studied polymorphisms included UCP2 (Ala55Val), UCP3 (C-55T), PPARA (G/C), PPARD (+294T/C), and PPARG (Pro12Ala). The G allele and the G/G genotype (PPARA) were overrepresented in the group of survivors and C/C (UCP3) genotype prevailed in the women of besieged Leningrad compared to relevant control groups of the persons of the same age who did not suffered hungry disaster. Feasible protective effects of PPARA gene allele G and C allele of UCP2 genes are briefly discussed.

Validation of an LC-MS bioanalytical method for quantification of phytate levels in rat, dog and human plasma.

Myo-inositol hexakisphosphate (phytate, IP6) is a naturally occuring compound whose determination in biological matrices is chanllenging. Several benefitial properties have been attributed to IP6 in parallel with the development of suitable analytical methodologies for its analytical determination in urine and some tissues. However, there is a lack of appropriate tools for its determination in plasma samples. In this paper, a direct, sensitive and selective bioanalytical method for the determination of IP6 based on LC-MS is presented. It is the first method published to quantify IP6 in plasma matrices directly through its molecular weight, being consequently a highly specific methodology. The method has been validated in rat, dog and human plasma, according to the acceptance criteria laid down in the FDA guidance Bioanalytical Method Validation. Accuracy and precision were not greater than 15% at medium and high concentrations and not greater than 20% at the LLOQ concentration. The mean absolute recovery obtained ranged from 78.74 to 102.44%, 62.10 to 87.21% and 61.61 to 86.99% for rat, dog and human plasma respectively. The LLOQ was 500ngmL(-1) due to the presence of endogenous IP6 in blank plasma samples and the limit of detection was within the range 30-80ngmL(-1).

[The new chemical preparation arbidol: its prophylactic efficacy during influenza epidemics]. / Novyi khimiopreparat arbidol: profilakticheskaia éffektivnost' vo vremia épidemii grippa.

In four controlled observations on the organized groups of students and industrial workers during the epidemics of influenza A in 1988-1989 Arbidol, a new chemopreparation, was found to be well tolerated and to produce a pronounced prophylactic effect when administered in a dose of 0.2 g (2 tablets of 0.1 g) daily for 10-18 days. After the 18-day prophylactic course of Arbidol the induction of serum interferon was found.