[Association of the polymorphic marker Glu23Lys in the KCNJ11 gene with hypertension in Kyrgyz patients]. / Assotsiatsiia polimorfnogo markera Glu23Lys gena KCNJ11 s razvitiem arterial'noi gipertonii u patsientov kirgizskoi natsional'nosti.

AIM: To study the association of the polymorphic marker Glu23Lys in the KCNJ11 with the development of hypertension in Kyrgyz patients. SUBJECTS AND METHODS: This case-control study enrolled 214 unrelated ethnic Kyrgyzes, in which a study group included 152 hypertensive patients (82 men and 70 women) and a control group consisted of 109 apparently healthy individuals (61 men and 48 women). The examinees' mean age was 55.2±10.1 years. Hypertension was verified when blood pressure (BP) was above 140/90 mm Hg. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to identify the polymorphic marker Glu23Lys in the KCNJ11 gene. RESULTS: In the hypertension and control groups, the prevalence of 3 genotypes (Glu23Glu, Glu23Lys, and Lys23Lys) of the Glu23Lys polymorphism in the KCNJ11 gene differed significantly (χ2=8.04; p=0.018). The Lys23Lys and Glu23Lys genotypes were statistically more frequently recorded in the hypertension group and the homozygous Glu23Glu genotype was, on the contrary, more common in the control group than in the study one. In the hypertension group, the 23Lys allele frequency was statistically significantly higher than that in the control one (χ2=7.36; p=0.0067). The carriage of the 23Lys allele increased the risk of hypertension by 1.68 times (odds ratio (OR), 1.68; 95% confidence interval (CI), 1.17-2.41), that of the Glu23 allele had, on the contrary, a protective effect (OR, 0.60; 95% CI, 0.41-0.86). CONCLUSION: The polymorphic marker Glu23Lys in the KCNJ11 gene is associated with hypertension in the Kyrgyzes. The 23Lys allele is a marker for the higher risk of hypertension.

[Risk of type 2 diabetes mellitus in the Kyrgyz population in the presence of ADIPOQ (G276T), KCNJ11 (Glu23Lys), TCF7L2 (IVS3C>T) gene polymorphisms]. / Risk razvitiia sakharnogo diabeta 2-go tipa v kyrgyzskoi populiatsii pri nalichii polimorfizmov G276T gena ADIPOQ, Glu23Lys gena KCNJ11 i IVS3C>T gena TCF7L2.

AIM: To analyze the association of genotype combinations of the polymorphic markers G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene with the development of type 2 diabetes mellitus (T2DM) in the Kyrgyz population. SUBJECTS AND METHODS: The investigation enrolled 23 Kyrgyz people, of whom there were 114 patients with T2DM and 109 without T2DM (a control group). T2DM was diagnosed in accordance with the WHO criteria (1999). The genotypes of ADIPOQ (G276T), KCNJ11 (Glu23Lys), and TCF7L2 (IVS3C>T) gene polymorphisms were identified using the restriction fragment length polymorphism analysis. RESULTS: When typing at the polymorphic loci G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene, the development of T2DM in the Kyrgyz population was associated with the T allele (odds ratio (OR), 1.68; p=0.025), the heterozygous G276T genotype (OR 1,8; p=0.036) in the ADIPOQ gene; the 23Lys allele (OR, 1.62; p=0.019) in the KCNJ11 gene; a two-locus genotype combination in the genes ADIPOQ/KCNJ11: G276T/Glu23Lys (OR, 4.88; p=0.0013), G276G/Lys23Lys (OR, 4.65; p=0.019), G276T/Glu23Glu (OR, 3.10; p=0.022), a two-locus genotype combination in the genes ADIPOQ/TCF7L2: G276T/СС (OR, 1.97; p=0.04); two-locus genotype combinations in the genes KCNJ11/TCF7L2: Lys23Lys/CC (ОR, 2.65; p=0.042), Glu23Lys/CT (OR, 3.88; p=0.027); and a three-locus genotype combination in the genes ADIPOQ/KCNJ11/TCF7L2: G276T/Glu23Lys/CT (OR, 14.48; p=0.02). CONCLUSION: The development of T2DM in the Kyrgyz population is genetically determined by ADIPOQ (G276T) gene, KCNJ11 (Glu23Lys), and TCF7L (IVS3C>T) gene polymorphisms with the predisposing value of the T allele of the heterozygous G276T genotype in the ADIPOQ gene; the 23Lys allele in the KCNJ1 gene; as well as by genotype combinations in the genes ADIPOQ/KCNJ11 (G276T/Glu23Lys, G276G/Lys23Lys, G276T/Glu23Glu); ADIPOQ/TCF7L2 (G276T/SS); KCNJ11/TCF7L2 (Lys23Lys/CC, Glu23Lys/CT); ADIPOQ/KCNJ11/TCF7L2 (G276T/Glu23Lys /CT). The IVS3C>T locus in the TCF7L2 gene is not independently statistically significantly associated with the development of T2DM; however, its predisposing effect has been identified in its combination with the variant genotypes of the polymorphic loci G276T in the ADIPOQ gene and Glu23Lys in the KCNJ11 gene.

Cerebral oxygenation in highlanders with and without high-altitude pulmonary hypertension.

NEW FINDINGS: What is the central question of this study? Cerebral hypoxia impairs cognitive function and exercise performance and may result in brain damage. Residents at high altitude, in particular those with high-altitude pulmonary hypertension, are prone to hypoxaemia due to the exposure to reduced barometric pressure and impaired pulmonary gas exchange. Whether highlanders have a reduced cerebral oxygenation has not been studied. What is the main finding and its importance? We found that despite a reduced arterial oxygen saturation, healthy highlanders and even those with pulmonary hypertension have a similar cerebral oxygenation to healthy lowlanders, suggesting that compensatory mechanisms protect long-term residents at high altitude from cerebral hypoxia. Abstract High-altitude pulmonary hypertension (HAPH), a chronic altitude-related illness, causes hypoxaemia and impaired exercise performance. We evaluated the hypothesis that haemodynamic limitation and hypoxaemia in patients with HAPH are associated with impaired cerebral tissue oxygenation (CTO) compared with healthy highlanders (HH) and lowlanders (LL). We studied 36 highlanders with HAPH and 54 HH at an altitude of 3250 m, and 34 LL at 760 m. Mean(±SD) pulmonary artery pressures were 34(±3), 22(±5) and 16(±4) mmHg, respectively (P < 0.05, all comparisons). The CTO was monitored by near-infrared spectroscopy along with pulse oximetry (peripheral arterial oxygen saturation, SpO2) during quiet breathing of room air (RA) and oxygen for 20 min each, and during hyperventilation with RA and oxygen, respectively. In HAPH, HH and LL breathing RA, SpO2 was 88(±4), 92(±2) and 95(±2)%, respectively (P < 0.001, all comparisons), and CTO was similar in the three groups, at 68(±3), 68(±4) and 69(±4)%, respectively (n.s., all comparisons). Breathing oxygen increased SpO2 and CTO significantly more in HAPH than in HH and LL. Hyperventilation (RA) did not reduce CTO in HAPH but did in HH and LL; hyperventilation (oxygen) increased CTO in HAPH only. Highlanders with and without HAPH studied at 3250 m had a similar CTO to healthy lowlanders at 760 m even though highlanders were hypoxaemic. The physiological response to hyperoxia and hypocapnia assessed by cerebral near-infrared spectroscopy suggests that healthy highlanders and even highlanders with HAPH effectively maintain an adequate CTO. This adaptation may be of particular relevance because adequate cerebral oxygenation is essential for vital brain functions.

[An Association Between T455C Polymorphism of Apolipoprotein C-III Gene, Insulin Resistance and Metabolic Syndrome Components].

AIM: to study an association between T455C apolipoprotein C-III (apo C-III) gene polymorphism, insulin resistance (IR), metabolic syndrome (MS) and its components in a Kyrgyz ethnic group. MATERIAL AND METHODS: 259 persons: 162 patients with MS and 97 sex and age matched controls without MS, diabetes mellitus and cardiovascular diseases were included in the study. Clinical examination with arterial blood pressure, anthropometric data measurement and laboratory tests for blood glucose and lipid parameters were performed in all included persons. In 140 patients test for immunoreactive serum insulin was done. DNA was extracted from blood cells and T455C polymorphism of apo C-III gene was determined by PCR method. RESULTS: In examined persons the most frequent was TC genotype as in group with MS as in controls. The difference on genotype's frequency between group was close to significant level (χ2 =5.48; p = 0.06) and odd ratio (OR) for MS between CC and TT carriers was 2.57 (95% CI 1.15-5.72); p = 0.019). Frequency of 455C allele in control group was--0.44 and in group with MS--0.54 (χ2 = 4.55; p = 0.036). In carriers of CC genotype there was noted that the frequency of IR (61.8% vs 23.1% vs 36.3%; p < 0.005), insulin level (11.9 [7.04-16.3] vs 5.73 [3.34-10.3] vs 7.54 [4.59-12.2] µIU/ml; p < 0.01) and HOMA index (3.14 [1.66-4.79] vs 1.46 [0.8-2.6] vs 2.05 [1.12-3.6]; p < 0.01) were significantly higher compared with TT and TC genotypes groups respectively. OR for IR between CC and TT carriers was 5.39 (95% CI 1.7-16.9; p = 0.0028). There also was an association between CC genotype and other MS components such as abdominal obesity (χ2--6.24; p--0.044, OR (95% CI--2.21 [1.03-4.82]) and high level of blood triglycerides (χ2--7.57; p--0.022, OR (95% CI) 2.5 [1.14-5.5]). CONCLUSION: In examined Kyrgyz ethnic population the most frequent was heterozygous TC genotype of T455C polymorphism of apo C-III. An association of 455C allele and CC genotype with MS, IR, abdominal obesity and high level of triglycerides was revealed. Key words: apolipoprotein C-III; T455C gene polymorphism; metabolic syndrome, insulin resistance.

[Association Between T455C Polymorphism of Apolipoprotein C-III Gene, Insulin Resistance and Metabolic Syndrome Components].

AIM: to study an association between T455C apolipoprotein C-III (apo C-III) gene polymorphism, insulin resistance (IR), metabolic syndrome (MS) and its components in a Kyrgyz ethnic group. MATERIAL AND METHODS: 259 persons: 162 patients with MS and 97 sex and age matched controls without MS, diabetes mellitus and cardiovascular diseases were included in the study. Clinical examination with arterial blood pressure, anthropometric data measurement and laboratory tests for blood glucose and lipid parameters were performed in all included persons. In 140 patients test for immunoreactive serum insulin was done. DNA was extracted from blood cells and T455C polymorphism.

[Association of adiponectin gene G276T polymorphism with the development of metabolic syndrome in ethnic Kyrgyz patients]. / Assotsiatsiya polimorfnogo markera G276T gena adiponektina s razvitiem metabolicheskogo sindroma u patsientov kirgizskoi natsional'nosti.

AIM: To study the association of adiponectin gene G276Т (ADIPOQ) polymorphism with the development of metabolic syndrome (MS) in ethnic Kyrgyz patients. MATERIAL AND METHODS: A total of 171 patients with MS (a study group) and 117 patients without MS (a comparison group) were examined. MS was defined on the basis of the modified ATP III criteria. The genotypes of the G276T polymorphism in the adiponectin gene were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: Dividing the MS and control groups by gender revealed statistically significant differences in the distribution of alleles and genotypes only among the women. There was a higher frequency of GT+TT genotypes (53% vs 34%; χ2=5.942; р=0.014) and T allele (30% vs 19%; χ2=4.489; р=0.0341) in the women with MS than in those without MS. Iin the ethnic Kyrgyz women, the T allele at the G276Т polymorphic locus in the ADIPOQ gene was associated with the development of MS (odds ratio (OR)=1.82; 95% confidence interval (CI) 1.04-3.19) and type 2 diabetes mellitus (T2DM) (OR=2.63; 95% CI, 1.05-6.56 ) with the high levels of leptin (p<0.05), glucose (p<0.05), triglycerides (OR=3.06; 95% CI, 1.05-8.93), low-density lipoprotein cholesterol (OR=2.80; 95% CI, 1,07-7.31) and with the lower level of high-density lipoprotein cholesterol (OR=2.9; 95% CI, 1.15-7.24). CONCLUSION: The risk for MS, T2DM, hyperglycemia, and dyslipidemia is related to the carriage of the T allele of the G276Т polymorphism in the ADIPOQ gene in ethnic Kyrgyz women.

[Association of the Arg399Gln polymorphisms of the XRCC1 gene with breast cancer risk in Kyrgiz women].

There were examined 219 women of Kyrgyz nationality (mean age 51 ± 9.7 years). 117 female with breast cancer (BC) and 102 apparently health controls. The diagnosis of breast cancer was confirmed histologically. DNA was prepared from whole blood samples. XRCC1 genotypes Arg399Gln were examined using polymerase chain reaction-restriction enzyme polymorphism (PCR-RFLP). The frequency of the variant 399Gln allele and heterozygous genotype Arg399Gln of the Arg399Gln polymorphism of the XRCC1 gene were significantly higher among women with breast cancer compared with control subjects (p < 0.05). The Arg399Gln polymorphism of the XRCC1 gene is associated with breast cancer risk in a Kyrgyz women when using additive model (χ² = 4,901; p = 0.0268) general model (χ² = 13,86; p = 0.0010) and dominant model of inheritance (χ² = 11.18; p = 0.0008). Women having the 399Gln allele had 1,57 fold (95% CI 1.7-2.30; p = 0.002) higher risk of developing BC compared with subjects carrying neither of these alleles. Individuals carrying the heterozygous genotype Arg399Gln had 2.77 fold (95% CI 1.6-4, p = 0.002) higher risk of BC. Thus, the heterozygous genotype Arg399Gln and 399Gln allele of XRCClgene are associated with an increased risk of breast cancer in Kyrgyz females.

[An association of the 825 polymorphism of the g protein 3 subunit with obesity in Kyrgyz population].

GOAL: To study an association of G protein (GP) 3 subunit 825 polymorphism with obesity in native Kyrgyzes. MATERIAL AND METHODS: 210 persons: 89 patients (female - 35, male - 54) with obesity (body mass index [BMI] more or equal 30 kg/m2) and 121 apparently healthy controls (38 female, 83 male) with normal BMI. Arterial blood pressure, anthropometric measurement and laboratory tests for blood glucose and lipid parameters were performed in all examined persons. DNA was extracted from blood cells and GP3 subunit 825 polymorphism was determined by PCR method. RESULTS: groups with TT and CT genotypes were combined together because of the rare frequency of TT genotype. Prevalence of + genotypes in group with obesity (0.72) was significantly higher than in controls - 0.52 (odds ratio 2.55, 95% confidence interval [CI] 1.31-4.23; =0.004). Arterial hypertension (45 vs. 31.3%; =0,049) and obesity (51.2 vs. 30%; p<0.01) occurred more often in + genotypes carriers compared with CC homozygotes. A logistic regression model for obesity showed significant effect of 825T allele (relative risk [RR] 2.89, 95% CI 1.25-6.7; =0.013) and irregular intake of vegetables (RR 3.47, 95% CI 1.52-7.94; =0.003) as predictors of obesity development independent of age, sex and physical activity level. In the regression model for arterial hypertension the 825T allele lost its significance after adjustment for obesity. CONCLUSION: GP3 subunit 825 allele in native Kyrgyzes is associated with obesity.

[Role of methyltetrahydrofolate reductase (MTHFR) gene polymorphism in the development of ischemic stroke in the dwellers of the Kyrgyz Republic].

AIM: To study the role of MTHFR gene polymorphism in patients with ischemic stroke (IS) in the Kyrgyz Republic. SUBJECTS AND METHODS: Molecular genetic testing of C677T polymorphism in the MTHFR gene was carried out in 107 Kyrgyz patients with prior IS. The patients were grouped according to the severity of motor impairments and the level of blood pressure (BP). The MTHFR C677T polymorphism was genotyped by polymerase chain reaction (PCR) using specific primers, followed by restriction of the resultant PCR products with the enzyme Hinf I. RESULTS: Severe motor impairments measured by the Scandinavian stroke scale was associated with the higher detection rate of the mutant TT genotypes of C677T polymorphism in the MTHFR gene (0.05 and 0.14; p < 0.04). As compared with stroke and normal BP, the development of stroke with high BP was associated with the presence of the mutant TT genotypes of C677T polymorphism in the MTHFR gene (1.9% versus 9.1%; p < 0.04). CONCLUSION: The increased detection rate of the mutant TT genotypes of C677T polymorphism in the MTHFR gene is associated with severe motor impairments (p < 0.04) in patients with IS and with the development of stroke during high BP.

[Association of C677T gene polymorphism of methylenetetrahydrofolate reductase with insulin resistance among Kirghizes].

AIM: To study an association of C677T gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) and insulin resistance (IR) among ethical Kirghizes. METHODS: 132 Kirghiz patients with IR according to HOMA index (n=132) and sex and age matched patients without IR, diabetes mellitus (DM) type 2 or metabolic syndrome (MS) (n=132) were included into this study. Measurements of blood pressure (BP), body mass index, waist and hip circumference, fasting blood sugar, insulin, lipid parameters and C677T gene polymorphism of MTHFR were performed in all patients. RESULTS: Frequency of CT and TT genotypes was significantly higher in patients with IR than in controls (2 - 7.22, p - 0,027, OR - 1.68, 95% confidence interval 1.13-2.5, p=0.027). T677 allele was also associated with obesity, hypertriglyceridemia and low level of high density lipoprotein cholesterol (HDL-C). CONCLUSION: In Kirghizes carriage of T677 allele of MTHFR gene was associated with IR, abdominal obesity, hypertriglyceridemia and low HDL-C level.

[Study of blood cholesterol and triglycerides in patients with acute myocardial infarction].

The levels of cholesterol (C) and triglycerides (TG) were studied by a standard biochemical assays and the amount of C and TG was examined by a fluorescence assay in 55 patients with complicated (n=32) and uncomplicated (n=23) acute myocardial infarction (AMI) and in 25 apparently healthy donors. The content of C did not differ significantly in the study groups. As compared with the controls, the patients with complicated AMI had lower values of C + TG (p < 0.01) and TG (p < 0.001). In the patients with uncomplicated AMI, these indices were also lower than those in the control, but not significantly. The patients with complicated AMI were found to have insignificantly lower levels of TG and C + TG than those with uncomplicated AMI. The lower level of TG seems to be responsible for the decreased C + TG amount detectable in AMI by a fluorescence assay.

Gene-to-gene interactions and the association of TP53, XRCC1, TNFα, HMMR, MDM2 and PALB2 with breast cancer in Kyrgyz females.

BACKGROUND: At present, little is known about the genetic background of breast cancer (BC) in Kyrgyz. Therefore, the aim of this study was to assess gene-to-gene interactions and the contribution of p.Arg72Pro (TP53 gene), p.Gln399Arg (XRCC1 gene), p.Arg194Trp (XRCC1 gene), g.4682G > A (TNFα gene), p.Val353Ala (HMMR gene), c.14 + 309 T > G (MDM2 gene) and g.38444 T > G (PALB2 gene) polymorphic loci in breast cancer (BC) risk in females of Kyrgyz ethnicity. METHODS: The case-control study comprised 103 females with histologically verified BC and 102 controls with no cancer. We used polymerase chain reaction-based restriction fragment length polymorphism to genotype polymorphic loci. RESULTS: Gln/Arg heterozygous variant of XRCC1 gene's p.Gln399Arg locus, as well as combined carriage of Arg/Gln//Arg/Pro of XRCC1/TP53; Arg/Gln//T/T of XRCC1/MDM2; Arg/Gln//G/G and Arg/Gln//G/A of XRCC1/TNFα, Arg/Gln//T/T of XRCC1/PALB2; Arg/Gln//Arg/Arg and Arg/Gln//Arg/Trp for p.Gln399Arg and p.Arg194Trp polymorphic loci of XRCC1 were associated with BC in Kyrgyz females. CONCLUSION: TP53, XRCC1, TNFα, HMMR, MDM2 and PALB2 genes' polymorphic site combinations appear to be candidate markers of genetic predisposition to BC in Kyrgyz population and prompt targeted personalized care.

[Characterization of the drug resistance spectrum of rifampicin-resistant M. tuberculosis to other first-line antituberculous drugs].

The spectrum of drug-resistance of rifampicin-resistant M. tuberculosis strains to other first-line antituberculous drugs was studied. Streptomycin resistance was found to be prevalent in the structure of monoresistance. Resistance to two agents--isoniazid and streptomycin--was more common in the structure of polyresistance; that to a combination of isoniazid, rifampicin, and streptomycin was seen in the structure of multidrug resistance. The rifampicin-resistant strains were also resistance to isoniazid and streptomycin in 95.1 and 98.7% of cases, respectively. Resistance to isoniazid, streptomycin, and ethambutol occurs more frequently when cytosine is substituted for thymidine (TCG-->TTG) in codon 513 of the rpoB gene.

[Analysis of mutations of multidrug-resistant M. tuberculosis strains in patients with tuberculosis in the Kyrghyz Republic].

Two hundred and seventy-eight M. tuberculosis DNA samples taken from patients with clinically confirmed pulmonary and extrapulmonary tuberculosis were studied. Mutations of the rpoB, inhA, katG, and ahpC genes were analyzed by using multiple drug-resistant (MDR) biochips. A hundred and twenty-nine (46%) rifampicin- and isoniazid-sensitive strains and 149 (54%) resistant ones were detected. Out of the 149 drug-resistant strains, resistance to one drug (rifampicin or isoniazid) was revealed in 7 (4.7%) and 48 (32.3%) cases, respectively. The strains simultaneously resistant to both drugs were detected in 94 (63%) cases. In the Republic of Kyrghyzstan, patients with drug-resistant pulmonary tuberculosis were observed to have more commonly multidrug-resistant strains (63%) than the strains resistant to one drug (rifampicin or isoniazid). In this republic, the main cause of rifampicin resistance of Mycobacterium tuberculosis is the Ser531-Leu mutation of the rpoB gene in codon 531 and the Ser315-->Thr of the katG gene in codon 315.

[Statistically mapping modeling of the spread of rifampicin-resistant M. tuberculosis strains in different regions of the Kyrghyz Republic].

Mapping modeling of the distribution of rifampicin-resistant tuberculosis was made in different regions of the Kyrghyz Republic. The results of determination of rifampicin resistance in Mycobacterium tuberculosis (MBT) by the biochip test were used to examine 904 MBT DNA samples taken when examining the patients living in different regions of the Kyrghyz Republic: Bishkek (n = 323), the Chui (n = 185), Issyk-Kul (n = 68), Naryn (n = 75), Talas (n = 47), Osh (n = 65), Dzhalal-Abad (n = 90), and Batken (n = 51) Regions. Comparison of the distribution of drug-resistant forms of tuberculosis by different regions revealed that rifampicin-resistant MBT strains were more frequently encountered in the densely populated regions of the republic - Bishkek and the Chui Region. Rifampicin resistance in MBT was caused by mutations in codons 531, 526, 522, 516, 511, 513, 512, and 513 of the rpoB gene. At the same time, there was a predominant selection of MBT with mutations in codons 531, 526, 516, and 511 in the republic. The spectrum of mutant MBT strains occurring in some regions varied. The broadest spectrum of genetic variability was observed in Bishkek and the Chui Region. Thus, Bishkek and the Chui Region are the hot points of concentration of mutant rifampicin-resistant MBT strains.

Sildenafil inhibits hypoxia-induced pulmonary hypertension.

BACKGROUND: This study investigated the effect of the phosphodiesterase 5 inhibitor sildenafil on the pulmonary vascular response to hypoxia in humans and mice. METHODS AND RESULTS: In a randomized, double-blind study, sildenafil 100 mg or placebo was given orally to 10 healthy volunteers 1 hour before breathing 11% O(2) for 30 minutes. Pulmonary artery pressure (PAP) was measured with an indwelling right heart catheter. The acute 56% increase in mean PAP produced by hypoxia during placebo treatment (mean PAP [mean+/-SD mm Hg]: normoxia 16.0+/-2.1 versus hypoxia 25.0+/-4.8) was almost abolished by sildenafil (normoxia 16.0+/-2.1 versus hypoxia 18.0+/-3.6), with no significant effect on systemic blood pressure. In the isolated perfused lung of wild-type and endothelial nitric oxide synthase (eNOS)-deficient mice, sildenafil markedly blunted acute hypoxic pulmonary vasoconstriction. Wild-type mice dosed orally with the drug (25 mg. kg(-1). d(-1)) throughout 3 weeks of exposure to hypoxia (10% O(2)) exhibited a significant reduction in right ventricular systolic pressure (placebo versus sildenafil: 43.3+/-9.9 versus 29.9+/-9.7 mm Hg, P<0.05) coupled with a small reduction in right ventricular hypertrophy and inhibition of pulmonary vascular remodeling. In eNOS mutant mice, sildenafil attenuated the increase in right ventricular systolic pressure but without a significant effect on right ventricular hypertrophy or vascular remodeling. CONCLUSIONS: Sildenafil attenuates hypoxia-induced pulmonary hypertension in humans and mice and offers a novel approach to the treatment of this condition. The eNOS-NO-cGMP pathway contributes to the response to sildenafil, but other biochemical sources of cGMP also play a role. Sildenafil has beneficial pulmonary hemodynamic effects even when eNOS activity is impaired.

[I/D relationship between polymorphism of ACE gene and progression of chronic glomerulonephritis].

AIM: To study prevalence of angiotensin-converting enzyme (ACE) gene polymorphism and its correlation with ACE level in Kyrgyz population suffering from chronic glomerulonephritis (CGN); to ascertain CGN progression and survival with reference to the genotype of ACE gene. MATERIAL AND METHODS: The above parameters were investigated in 76 CGN patients (mean age 34.1 +/- 1.9 years) and 48 healthy controls matched by sex and age. Amplification of the polymorphic site of the ACE gene was made with polymerase chain reaction. Spectrofluorimetry measured ACE concentration in the serum. Progression of CGN was assessed by reciprocal creatinine. Survival of the patients was calculated according to the Kaplan-Meyer method. RESULTS: The ACE genotype distribution corresponded to the Hardi-Weinberg equilibrium. However, a significant difference in the frequency of genotypes and alleles between CGN and control patients was not revealed. The activity of serum ACE in CGN and healthy subjects was noticeably higher in DD genotype than that in genotypes II and ID (P < 0.02). The former had a significantly higher level of total cholesterol and much lower glomerular filtration rate in a rapid progression of the disease estimated by reciprocal creatinine and higher 5- and 10-year survival compared to genotypes II and ID (P < 0.05). CONCLUSION: Development of CGN is not associated with any genotype of ACE gene in Kyrgyz population. At the same time, deletion polymorphism of ACE gene may serve as a predictor for CGN progression.

[Use of biological microchips in the determination of drug-resistance of Mycobacterium tuberculosis to rifampicin].

The present-day problems in tuberculosis control are associated with a difficulty in detecting Mycobacterium tuberculosis (MBT) in due time and in determining its drug sensitivity by conventional microbiological assays. The determination of the drug sensitivity of MBT takes much time from 2 weeks to 3 months, which fails to initiate and perform specific therapy timely. Molecular genetic techniques, including biochip analysis, yield results in 24-48 hours, which solves the problem of choosing and initiating adequate antibacterial therapy in the shortest possible time after tuberculosis is diagnosed. To assess the situation associated with the prevalence of rifampicin-resistant tuberculosis, by using the biochip analysis, the authors have examined 501 patients with tuberculosis who live in the Kyrghyz Republic. Drug resistance has been found in 40.3% of the examinees. At the same time, their primary and secondary drug resistance is 25.7 and 61.8%, respectively. In tuberculosis patients living in Kyrghyzstan, rifampicin resistance of MBT is more frequently due to mutations in 531 (59.2%), 526 (20.8%), and 516 (8.0%) codons in the rpoB gene.