Four-hour evaluation of a medical food in subjects with type 2 diabetes receiving oral hypoglycemic medication

Background: Postprandial hyperglycemia is an independent risk factor for diabetes-associated complications in individuals with type 2 diabetes. Dietary modification plays an important role in glycemic control. This study was to examine the efficacy of a diabetes specific formula (DSF) during a 4-hour postprandial meal tolerance test (MTT) in Russian subjects with type 2 diabetes receiving oral hypoglycemic medication. Methods: In a randomized, cross-over design, 168 eligible subjects from 11 study centers consumed, in a random order, the DSF (230 mL) or a common light hospital breakfast (i.e. standard meal) on two different occasions. The amounts of macronutrients were similar between the two meals providing ~200 kcal, 11 g protein, 26 g carbohydrate and 8 g fat. Capillary glucose levels were measured at baseline (before meal consumption), and post-meal consumption at 30, 60, 90, 120, 180 and 240 min. Results: The DSF was well tolerated in all subjects. There were 111 subjects completed the study per protocol (mean ± SEM: age: 58.6 ± 0.8 yr, BMI: 31.8 ± 0.42 kg/m2, waist circumference: 101 ± 1.3 cm, HbA1c: 8.0% ± 0.1%). Glucose levels reached peak values at 60 min (median) and the lowest levels at the end of the 240-min MTT test. The mean positive area under the curve (PAUC), the primary outcome, was significantly smaller after DSF consumption (mean ± SEM: 183.02 ± 18.74, median: 132.55) than the PAUC after consumption of the standard meal (mean ± SEM: 239.95 ± 23.11, median: 166.89;p = 0.027). The actual and adjusted peak glucose concentrations were similar between the two treatments. Conclusions: In patients with type 2 diabetes receiving oral hypoglycemic agents, compared to a hospital meal, the DSF improves postprandial glucose control. Combining results from earlier studies, long-term use of DSF may be beneficial to improve glucose management and decrease diabetes-associated complications.

Biodegradable Protection for Medical Devices with Medical Drugs Controlled Separation

With the aim of creating biodegradable materials for medical devices clinical appointments with high hemocompatibility we have developed a new polymer product.The basis of this product is plasticized by polyethylene glycol bacterial copolymer of hydroxybutyrate and oxovalerate. A well-known antitbrombotic supplement--acetylsalicylic acid has been added to improve hemocompatibility in the polymer. The results of our studies showed a controlled prolonged separation of acetylsalicylic acid from polymeric material in the blood. We studied in vitro the dynamics of liberation of acetylsalicylic acid from polymeric coatings. It was shown that the concentration of polyethylene glycol and the thickness of the polymer layer can affect the rate of diffusion of acetylsalicylic acid from polymer films.

Mitochondrial dysfunction and mitochondrial DNA mutations in atherosclerotic complications in diabetes

Mitochondrial DNA(mtDNA) is particularly prone to oxidation due to the lack of histones and a deficient mismatch repair system.This explains an increased mutation rate of mtDNA that results in heteroplasmy,e.g.,the coexistence of the mutant and wild-type mtDNA molecules within the same mitochondrion.In diabetes mellitus,glycotoxicity,advanced oxidative stress,collagen cross-linking,and accumulation of lipid peroxides in foam macrophage cells and arterial wall cells may significantly decrease the mutation threshold required for mitochondrial dysfunction,which in turn further contributes to the oxidative damage of the diabetic vascular wall,endothelial dysfunc-tion,and atherosclerosis.

Association of the level of heteroplasmy of the 15059G>A mutation in the MT-CYB mitochondrial gene with essential hypertension

AIM: To examine whether the heteroplasmy level for 15059G】A mutation in the mitochondrial genome might be associated with essential hypertension. METHODS: This cross-sectional study involved 196 unrelated participants randomly selected from general population (90 males and 106 females) who underwent a regular medical check-up at the Institute for Ath-erosclerosis Research (Moscow, Russia). One hundred and twenty of them (61%) had essential hypertension, and 76 (39%) were apparently healthy normotensive persons. The level of heteroplasmy for 15059G】A mutation occurring in the coding region of cytochrome b gene (MT-CYB) of mtDNA isolated from the blood leukocytes, was quantified using DNA pyrosequencing method. RESULTS: The 15059G】A heteroplasmy level ranged between 4% and 83%, with a median level of 31%. Between the upper and lower quartiles of 15059G】A heteroplasmy distribution, significant differences were observed for patients’ age, systolic blood pressure, and triglyceride levels. 15059G】A heteroplasmy correlated both with age (r = 0.331, P 【 0.001) and the presence of hypertension (r = 0.228, P = 0.002). Regression analysis revealed that the age explains 12% variability of 15059G】A heteroplasmy, and hypertension independently explains more 5% variability. The 15059G】A heteroplasmy exceeding 31% was found to be significantly associated with a higher risk of essential hypertension (odds ratio 2.76; P (Fisher) 0.019]. The study participants with high 15059G】A heteroplasmy level were found to have significantly higher age (P 【 0.001) and the prevalence of essential hypertension (P = 0.033), as compared to those with low 15059G】A heteroplasmy level. These observations suggested a positive correlation between the level of 15059G】A heteroplasmy and essential hypertension. CONCLUSION: This study provides the evidence of association of mtDNA 15059G】A mutation heteroplasmy with essential hypertension.

Anti-apoptotic effect of retinoic acid on retinal progenitor cells mediated by a protein kinase A-dependent mechanism

Retinal progenitor cells （RPCs） are neural stem cells able to differentiate into any normal adult retinal cell type, except for pigment epithelial cells. Retinoic acid （RA） is a powerful growth/differentiation factor that generally causes growth inhibition, differentiation and/or apoptosis. In this study, we demonstrate that RA not only affects mouse RPC differentiation but also improves cell survival by reducing spontaneous apoptotic rate without affecting RPC proliferation. The enhanced cell survival was accompanied by a significant upregulation of the expression of protein kinase A （PKA） and several protein kinase C （PKC） isoforms. Treatment of cells grown in RA-free media with 8-bromoadenosine3＇,5＇-cyclic monophosphate, a known activator of PKA, resulted in an anti-apoptotic effect similar to that caused by RA; whereas the PKA inhibitor N-[2-（p-bromocinnamylamino）ethyl]-5-isoquinolinesul- fonamide dihydrochloride led to a significant （-32%） increase in apoptosis. In contrast, treatment of RPCs with any of two PKC selective inhibitors, 2,2＇,3,3＇,4,4＇-hexahydroxy-1,1 ＇-biphenyl-6,6＇-dimethanol dimethyl ether and bisindolylmaleimide XI, led to diminished apoptosis; while a PKC activator, phorbol 12-myristate 13-acetate, increased apoptosis. These and other data suggest that the effect of RA on RPC survival is mostly due to the increased anti-apoptotic activity elicited by PKA, which might in turn be antagonized by PKC. Such a mechanism is a new example of tight regulation of important biological processes triggered by RA. Although the detailed mechanisms remain to be elucidated, we provide evidence that the pro-survival effect of RA on RPCs is not mediated by changed expression of p53 or bcl-2, and appears to be independent of 15-amyloid, Fas ligand, TNF-α, ganglioside GM1 and ceramide C 16-induced apoptotic pathways.

Obesity trends in Russia. The impact on health and healthcare costs

Similar to most developed countries, obesity rates inRussiahave been steadily increasing. This has led to a high burden of obesity related diseases and associated healthcare costs. The micro-simulation model has been utilized to project body mass index (BMI) and BMI related disease burden and healthcare costs. Incidence, mortality, survival and healthcare costs were collected for thirteen diseases. The results have been simulated for 3 hypothetical scenarios to project a potential impact of policy interventions: 1) assuming no reduction in BMI;2) 1% reduction in mean BMI across the population;3) 5% reduction in mean BMI across the population. Nearly 58% of the female population was obese (BMI ≥30 kg/m2) or overweight (BMI 25 -29.9 kg/m2) in 2010, and the prevalence is projected to decrease to 54% in 2050. The rates are predicted to increase for men from 51% in 2010 to 76% in 2050. The prevalence rates will triple for some obesity-related diseases. A one percent decrease in BMI across the population will save more than two billion US Dollars in 2030 and 2050. Despite female obesity prevalence starting at a higher point than the men, obesity is predicted to increase in males but not females. Disease and economic burden attributed to these obesity rates are still severe and the country should implement strong policies to tackle the obesity epidemic.

New Plant Growth Regulators for Fibre Flax

Tests of new natural non-polluting regulators of growth Verva （vegetative terpenoids from Abies sibirica） and Larixin （vegetative flavonoids from Larix） on growth, development and productivity of fibre flax are conducted. The level of phytohormones in vegetating plants （IAA, ABA, zeatine and zeatinriboside） is studied. Preparations stimulate germination of seeds and growth of plants. Field experiment fixed yield increase of flax straw and the seeds of flax-fibre with the use of growth regulators. Industrial experiment represents VERVA product effectiveness on yields increase of flax straw, seeds and flax fiber output.

COMPARATIVE EVALUATIVE STUDY OF EFFICIENCY AND SAFETY OF THE US-AGE OF TOPICAL CARBOANHYDRASE INHIBITORS

No considerable difference between efficiency of topical car-boanhydrase inhibitors was detected during comparison of their hypotensive effect after single usage in healthy volunteers and glaucoma patients (40 participants). Maximal hypotensive effect occurred in four hours after study started and average IOP decreasing was one percent from primary level. When using

LIMITED CONTROLLED INFLAMMATION PROCESS IN THE TREATMENT OF GLAUCOMATOUS OPTIC NEUROPATHY

Principles of autobiotherapy non-infectious inflammatory focus is created for uncertain period of time/ inflammatory mediators should have an opportunity to penetrate through retina and optic nerve disc/ unfavorable effects of inflammation are blocked by pharmacotherapy. Were developed and checked 3 variants

Genetic Analysis of 17 Children with Hunter Syndrome:Identification and Functional Characterization of Four Novel Mutations in the Iduronate-2-Sulfatase Gene

Mucopolysaccharidosis type II （MPS II） is a rare X-linked disorder caused by alterations in the iduronate-2-sulfatase （IDS） gene. In this study, IDS activity in peripheral mononuclear blood monocytes （PMBCs） was measured with a fluorimetric enzyme assay. Urinary glycosaminoglycans （GAGs） were quantified using a colorimetric assay. All IDS exons and intronic flanks were bidirectionally sequenced. A total of 15 mutations （all exonic region） were found in 17 MPS II patients. In this cohort of MPS II patients, all alterations in the IDS gene were caused by point nucleotide substitutions or small deletions. Mutations p.Arg88His and p.Arg172＊ occurred twice. All mu- tations were inherited except for p.Gly489Alafs＊7, a germline mutation. We found four new mutations （p.Ser142Phe, p.Arg233Gly, p.Glu430＊, and p.Ile360Tyrfs＊31）. In Epstein-Barr virus （EBV）-immortalized PMBCs derived from the MPS II patients, no IDS protein was detected in case of the p.Ser142Phe and p.Ile360Tyrfs＊31 mutants. For p.Arg233Gly and p.Glu430＊, we observed a residual expression of IDS. The p.Arg233Gly and p.Glu430＊ mutants had a residuary enzymatic activity that was lowered by 14.3 and 76-fold, respectively, compared with healthy controls. This observation may help explain the mild disease phenotype in MPS II patients who had these two mutations whereas the p.Ser142Phe and p.Ile360Tyrfs＊31 mutations caused the severe disease manifestation.