[Ala54Thr polymorphism of the fatty acid transporter gene (FABP2) in patients with type 2 diabetes mellitus in Yakutia].

AIM: To study the contribution of the Ala54Thr genetic polymorphism of the FABP2 gene to the risk of developing type 2 diabetes mellitus among the Yakut population. MATERIALS AND METHODS: The study included participants who filled out a questionnaire approved by the Local Committee on Biomedical Ethics at the Yakut Science Centre of complex medical problems and voluntarily signed an informed consent to conduct a genetic study. The sample consisted of 181 patients of the endocrinological department of the Republican Hospital No. 2 of the State Budgetary Institution "Center for Emergency Medical Care" with a diagnosis of type 2 diabetes. The comparison group was a sample of 336 volunteers without chronic diseases of the Yakut ethnicity. For molecular genetic analysis, genomic DNA samples were isolated from whole blood. Single nucleotide polymorphism was determined by polymerase chain reaction followed by analysis of restriction fragment length polymorphism. RESULTS: Study showed that polymorphism in the FABP2 gene has an impact on anthropometric parameters and blood biochemical parameters. The risk of developing type 2 diabetes was 1.7 times higher in carriers of the Ala/Thr genotype (odds ratio 1.755, 95% confidence interval - 1.212-2.542; p<0.005) compared with carriers of other genotypes. When comparing the average biochemical values, the levels of aspartate transaminase, alanine aminotransferase, glucose and total bilirubin in homozygous carriers of the Ala/Ala genotype were significantly lower than in carriers of other genotypes (р<0.05). Carriers of the heterozygous Ala/Thr genotype (р<0.05) had the highest level in terms of aspartate aminotransferase and alanine aminotransferase. The highest indicator of the average level of HbA1c and an indicator of total bilirubin were carriers of the Thr/Thr genotype (р<0.05). CONCLUSION: The high prevalence of the negative Thr allele among the Yakut population is probably associated with living conditions in the North, as well as in the traditional type of diet.

Effects of Heavy Metals on the Metabolome of Pinus sylvestris (Pinaceae).

The effects of Cu, Ni, and Cd on the Pinus sylvestris metabolome was studied in experimental conditions by gas chromatography-mass spectrometry (GC-MS). Structural changes in plant metabolite network became detectable on day 6 of exposure to the metals, 3-6 days earlier than visual signs of toxicity developed. Differences at the metabolome level arose earlier in a control group of plants, and specific effects of particular metals on the plant metabolome became distinct on day 9. Both nature and concentration of a metal equally contributed to the plant metabolome clustering. Plant responses (changes in concentrations of individual metabolites) to metal exposure substantially differed depending on the metal concentration (1 or 5 mM) and nature. The effects of Cd and Cu were generally similar, while the effect of Ni was often different. Dynamic changes visualized in plant metabolite matrix reflected the changes in its correlation structure, rather than depending on the set of particular compounds.

[New betulin derivatives in combination with rimantadine for inhibition of influenza virus reproduction].

The preliminary studies mainly revealed comparable inhibition activities of 3-oxime of betulonic acid, 3beta-O-acetyl-28-O-hemiphthalate of betulin and 3,28-dioxime of betulin against reproduction of influenza viruses A (H1N1), A (H7N1), A (H3N2) and B, as well as against the strains of influenza virus A (H1N1) with intrinsic resistance to rimantadine and A (H7N1) with acquired resistance to the drug. The level of the activity depended on the system used for the virus reproduction. The highest level was observed under conditions providing higher permissibivity, i.e. in the chick embryo fibroblast cell culture for A (H7N1) and in fragments of chick embryo chorioallantoic membranes (for all the viruses). In the experiments with virus A/FPV/Rostock/34 (H7N1) in the chick embryo fibroblast cell culture the average effective concentrations (EC50) of the triterpene compounds were 10.4-17.5 mcM in comparison to EC50 of rimantadine (0.014 mcM). The use of every of the compounds in combination with rimantadine resulted in a 2-16 times decrease of their EC50 and correction of the concentration-effect relation of rimantadine. However, when rimantadine was used alone within the higher range of the nontoxic concentrations (11.6-57.6 mcM). its antiviral properties were significantly less pronounced. As a result the virus titer difference in comparison to the control within the above range of the rimantadine concentrations increased from < 1 to > 2.35 Ig PPU/ml and the relations of the maximal tolerance concentrations of the compounds to their EC50 increased 1.7-15.9 times.

[Synthesis and antiviral activity of lupane triterpenoids with modified cycle E].

A reductive transformation of the peroxide products of ozonolysis of derivatives of 3beta-O-acetyl-22(17-->28)-abeo-lupa-17(28),20(29)-diene and the subsequent intramolecular ketalization led to a compound with a trioxane fragment. This is a new approach to a skeletal modification of triterpenoid cycle E. An activity of the synthesized compounds was found toward the viruses of type A influenza and herpes simplex.

[Synthesis and antiviral activity of amides and conjugates of betulonic acid with amino acids]. / Sintez i protivovirusnaia aktivnost' amidov i kon''iugatov betulonovoi kisloty s aminokislotami.

Betulonic acid amides with aliphatic and heterocyclic amines and with L-amino acids were synthesized by the acid chloride method. Betulonic acid amide and L-methionine derivatives of betulonic acid and its 3-oxime effectively inhibit the influenza A virus. Betulonic acid octadecylamide is active against the herpes simplex type 1 virus. The conjugate of betulonic acid 3-oxime with L-methionine is also active toward HIV-1. The tested compounds mainly show no activity toward the ECHO6 virus, which is devoid of a coat. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 1; see also http://www.maik.ru.

Lupane triterpenes and derivatives with antiviral activity.

Betulin and betulinic acid have been modified at the C-3 and C-28 positions and the antiviral activity of derivatives has been evaluated in vitro. It was found that simple modifications of the parent structure of lupane triterpenes produced highly effective agents against influenza A and herpes simplex type 1 viruses.

[Synthesis and antiviral activity of hydrazides and substituted benzalhydrazides of betulinic acid and its derivatives]. / Sintez i protivovirusnaia aktivnost' gidrazidov i zameshchennykh benzal'gidrazidov betulinovoi kisloty i ee proizvodnykh.

New nitrogen-containing derivatives of betulinic and betulonic acids, hydrazides and N'-benzalhydrazides, were synthesized. Their antiviral activities toward of influenza A virus, herpes simplex type I virus, enterovirus ECHO6, and HIV-1 were studied in vitro. Betulinic acid 3-oxime was found to have the highest activity against the influenza virus. Betulonic acid, betulinic acid 4-chlorobenzalhydrazide, betulonic acid 3-oxime benzalhydrazide, and betulinic acid hydrazide inhibited the replication of herpes simplex type I virus. Betulinic acid hydrazide also showed antiviral activity toward HIV-1. All the derivatives of betulinic acid under study displayed a low antiviral activity toward enterovirus ECHO6.

Antiviral activity of betulin, betulinic and betulonic acids against some enveloped and non-enveloped viruses.

Antiviral properties of betulin, betulinic and betulonic acids were investigated in cell cultures infected with herpes simplex type I, influenza FPV/Rostock and ECHO 6 viruses. All studied triterpenes were active against herpes simplex virus. Betulin and especially betulinic acid also suppressed ECHO 6 virus reproduction.

[Synthesis and antiviral activity of ureides and carbamates of betulinic acid and its derivatives]. / Sintez i protivovirusnaia aktivnost' ureidov i karbamatov betulinovoi kisloty i ee proizvodnykh.

Ureides and carbamates of betulinic acid and its derivatives were prepared in good yields by interaction of betulinic acid, betulonic acid, and betulonic acid 3-oxime with amines, amino acids, and alcohols. Ureides of betulonic acid containing L-Val and L-Met residues were found to be effective against herpes simplex type 1 virus. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2003, vol. 29, no. 6; see also http://www.maik.ru.

[Antiviral activity of 2'-deoxy-2'-fluoroguanosine against influenza and herpes simplex viruses in cultured cells]. / Protivovirusnaia aktivnost' 2'-dezoksi-2'-ftorguanozina v otnoshenii virusov grippa i prostogo gerpesa v kul'turakh kletok.

High antiviral activity of 2'-deoxy-2'fluoroguanosine (2'-D-2'-FG) was observed in chicken embryo cells infected with FPV/Rostock/34 (H7N1) influenza virus and herpes simplex virus (HSV) type I (strain 1C). 50% inhibitory concentration (IC50) of 2'-D-2'-FG was 1.44 microM for FPV and 0.093 microM for HSV. IC50 of remantadine hydrochloride, ribavirin (FPV), and acycloguanosine (HSV) were < 0.46, 14.4, and 0.08 microM, respectively. Anti-HSV activity was confirmed in Vero cells: IC50 < 0.34 microM for 2'-D-2'-FG and IC50 < 0.044 microM for acycloguanosine.

Chemical and enzymatic synthesis and antiviral properties of 2'-deoxy-2'-fluoroguanosine.

Chemical and enzymatic methods were employed for the synthesis of the title compound, 2'F-Guo 7. High antiviral activity of 2'F-Guo was established in chick embryo cells infected with influenza virus FPV/Rostock/34 (H7N1) and herpes simplex virus (HSV) type I (1C strain).

[Change in the sensitivity of influenza virus, replicating in the presence of rimantadine, to antiviral agents]. / Izmenenie chuvstvitel'nosti virusa grippa, razmnozhivshegosia v prisutstvii remantadina, k protivovirusnym preparatam.

A variant obtained by a single passage of the initial FPV in the presence of 25 micrograms/ml rimantadine is more resistant to the drug than the parental virus. Sensitivity to rimantadine is higher in a variant obtained similarly by cell culture infection with rimantadine-resistant FPV. Potentiation of the antiviral effect of a combination of ribavirin (12-25 micrograms/ml) and rimantadine (0.1-6 micrograms/ml) is decreased or null if rimantadine dose is increased to 12-25 micrograms/ml; this phenomenon does not depend on the sensitivity of infective virus to rimantadine. Antiviral effect of drug combination with a high concentration of rimantadine is due to ribavirin alone.

[Polypeptides from influenza virus, obtained in the presence of high concentrations of rimantadine]. / Polipeptidy virusa grippa, poluchennogo v prisutstvii vysokikh kontsentratsii remantadina.

FPV/Rostock obtained in the presence of remantadine (25 micrograms/ml) is studied. This variant of the virus is characterized by a decreased amount of M1-protein. Its buoyant density in urograffin density gradient is 1.20 gamma/cm3 vs. 1.18 and 1.175 g/cm3 for initial FPV and remantadine-resistant FPV, respectively. Purification and concentration decreases the hemagglutinating activity of the virus 5-10 times more intensely than that of initial and remantadine-resistant FPV. On the other hand, the production of virus-specific proteins and intracellular distribution of hemagglutinin in this virus variant were not changed. The changes associated with a decrease of hemagglutinin and M1-protein content in virions are believed to manifest at a later stage preceding virion release from the cell.

[Features of the antiviral effect of carbocyclic compounds depending on their concentration]. / Osobennosti protivovirusnogo deistviia soedinenii karbotsiklicheskogo riada v zavisimosti ot ikh kontsentratsii.

Antiviral agents and new agents possessing antiviral properties and characterized by a carbocyclic (carcass) structure were shown to differ from other, specifically, heterocyclic compounds, by the presence of a range from the maximally effective to maximally tolerable concentrations, the antiviral effect decreasing in this range of concentrations. This feature was observed in cell cultures, chick embryos, and laboratory animals in experiments with different influenza viruses and RS virus.

[State of the microcirculation and its relation to gastric function and structural changes in the gastroduodenal zone in recurrent peptic ulcer]. / Sostoianie mikrotsirkuliatsii i ee sviaz' s funktsiiami zheludka i strukturnymi izmeneniiami v gastroduodenal'noi zone pri retsidive iazvennoi bolezni.

A total of 108 patients with peptic ulcer were entered into the study. Examination of the microcirculation in the eye conjunctiva and microvessels of biopsy specimens of the mucous membrane taken from ulcerous areas revealed that disease relapses were marked by pronounced disorders of the end blood flow. The extent of the disorders was found to be determined by the activity and localization of the pathological process, structural alterations in the mucous membrane of the gastroduodenal area, and by gastric functions.