[3D modeling for planning of minimally invasive approach to the orbit]. / Ispol'zovanie 3D-modelirovaniya dlya planirovaniya minimal'no invazivnogo dostupa k oblasti orbity. Sluchai iz praktiki i obzor literatury.

OBJECTIVE: To demonstrate own experience in 3D modeling for planning of minimally invasive approach to the orbit and anterior skull base. MATERIAL AND METHODS: A 17-year-old patient admitted to the Department of Pediatric Neurosurgery with complaints of decreased visual acuity of the left eye, lacrimation and exophthalmos. MRI revealed a tumor of the left orbit. We have preoperatively modeled frontoorbital region, anterior skull, as well as eyeball and tumor within the same model. Considering young age and potentially favorable prognosis of disease, we preferred a minimally invasive intervention (microsurgical resection of tumor through minimally invasive frontoorbital access). RESULTS: Total resection of tumor was followed by examination of anterior skull base. There was postoperative regression of visual disturbances, lacrimation and exophthalmos. Sutures were removed after 5 days, and the patient was discharged. CONCLUSION: Minimally invasive frontoorbital access is adequate for approach to the orbit, anterior and middle cranial fossa, adequate resection of orbital tumor and examination of anterior skull base. 3D modeling is an additional preoperative tool to improve the quality of preoperative planning and facilitate intraoperative navigation.

Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium.

BACKGROUND: Genome-wide association studies have identified novel genetic associations for asthma, but without taking into account the role of active tobacco smoking. This study aimed to identify novel genes that interact with ever active tobacco smoking in adult onset asthma. METHODS: We performed a genome-wide interaction analysis in six studies participating in the GABRIEL consortium following two meta-analyses approaches based on 1) the overall interaction effect and 2) the genetic effect in subjects with and without smoking exposure. We performed a discovery meta-analysis including 4,057 subjects of European descent and replicated our findings in an independent cohort (LifeLines Cohort Study), including 12,475 subjects. RESULTS: First approach: 50 SNPs were selected based on an overall interaction effect at p<10-4. The most pronounced interaction effect was observed for rs9969775 on chromosome 9 (discovery meta-analysis: ORint = 0.50, p = 7.63*10-5, replication: ORint = 0.65, p = 0.02). Second approach: 35 SNPs were selected based on the overall genetic effect in exposed subjects (p <10-4). The most pronounced genetic effect was observed for rs5011804 on chromosome 12 (discovery meta-analysis ORint = 1.50, p = 1.21*10-4; replication: ORint = 1.40, p = 0.03). CONCLUSIONS: Using two genome-wide interaction approaches, we identified novel polymorphisms in non-annotated intergenic regions on chromosomes 9 and 12, that showed suggestive evidence for interaction with active tobacco smoking in the onset of adult asthma.

Effect of Doxazosin on Autonomic Nervous Control and Urodynamics of Rat Urinary Bladder during Modeled Infravesical Obstruction.

The therapeutic effect of doxazosin (40 µg/kg/day over one month) on urinary bladder was examined in female rats with modeled chronic infravesical obstruction (IVO) produced by graduated mechanical constriction of the proximal urethral segment. In one month, IVO induced a pronounced vesical hypertrophy both in treated and untreated rats that manifested in increased bladder weight and capacity, the latter increment being pronouncedly greater in treated rats. In untreated IVO rats, infusion cystometry revealed elevated basal intravesical pressure of void bladder P0, markedly increased maximal (premicturitional) pressure Pmax, and increased amplitude of spontaneous oscillations of intravesical pressure ΔPdet in filled bladder. Doxazosin produced no significant effect on Pmax rise during IVO, but prevented elevation of P0 and increment of ΔPdet in filled bladder. During gradual filling of urinary bladder in control (intact) rats, the parasympathetic vesical influences increased progressively, while in untreated IVO rats, the adrenergic influences prevailed even at maximal filling of the bladder. In IVO rats, doxazosin prevented the bias of the sympathetic-parasympathetic balance in the filled bladder in favor of sympathetic influences, but did not prevent this bias in a void bladder. It is hypothesized that α-adrenoblockers improve micturition during IVO caused by benign prostatic hyperplasia not only by decreasing the urethral resistance to urine flow due to down-regulation of prostate smooth muscle tone, but also by a direct action of these blockers on detrusor adrenergic receptors and central structures involved in urinary bladder control.

[Association of the -844G>A polymorphism in the catalase gene with the increased risk of essential hypertension in smokers]. / Assotsiatsiya polimorfizma -844G>A gena katalazy s povyshennym riskom razvitiya arterial'noi gipertonii u kuril'shchikov.

AIM: To investigate whether the functionally relevant -844G>A promotor polymorphism in the catalase (CAT) gene is associated with the development of essential hypertension (EH). SUBJECTS AND METHODS: The investigation enrolled 2,339 unrelated ethnic Russian people, including 1,269 EH patients and 770 apparently healthy individuals. Genotyping of CAT -844G>A (rs769214) polymorphism was performed using a TaqMan real-time polymerase chain reaction assay. RESULTS: The -844A allele (odds ratio (OR)=1.31; 95% confidence interval (CI), 1.04 to 1.64; р=0.02) and the -844AA genotype (OR=1.41; 95% CI, 1.02 to 1.94; р=0.03) were found to be related to a higher risk of EH in the smokers. No association was found between this polymorphism and EH risk in the non-smokers. CONCLUSION: Smoking is a predisposing factor for development of EH in CAT -844AA genotype carriers.

[Granulomatous inflammation in the bed of resected cerebral cavernoma in a child, caused by a hemostatic agent].

OBJECTIVE: The study presents a clinical observation of foreign body granuloma, which is rare productive inflammation, developed on treatment with a hemostatic material upon removal of cerebral cavernoma. MATERIAL AND METHODS: A 4-year-old boy operated on for left parietal lobe cavernoma was diagnosed with a mass lesion during a follow-up MRI examination 4 months after surgery. The patient was re-operated in connection with suspected abscess formation. The pathological tissue was subjected to the histological and immunohistochemical examination. RESULTS: Inflammation was accompanied by the formation of foreign body granulomas, and, in some areas, had immune nature with signs of focal destructive vasculitis, delayed maturation of the granulation tissue, and disturbance of the current organization and encapsulation processes. It is worth noting that granulomatous inflammation around a hemostatic material in the brain has no specific features during introscopy and mimics an abscess or tumor recurrence. CONCLUSION: The use of hemostatic materials upon resection of cerebral cavernous malformations may cause formation of granuloma mimicking disease relapse or abscess in the long term period. To prevent granulomatous inflammation, removal of a hemostatic material, if possible, from the surgical field is recommended when reliable hemostasis is achieved.

[Genetic and biochemical mechanisms of involvement of antioxidant defense enzymes in the development of bronchial asthma].

In the present review we have analyzed and summarized recent literature data on genetic and biochemical mechanisms responsible for involvement of antioxidant defense enzymes in the etiology and pathogenesis of bronchial asthma. It has been shown that the mechanisms of asthma development are linked with genetically determined abnormalities in the functioning of antioxidant defense enzymes. These alterations are accompanied by a systemic imbalance between oxidative and anti-oxidative reactions with the shift of the redox state toward increased free radical production and oxidative stress, a key element in the pathogenesis of bronchial asthma.

[The combined effect of E298D polymorphism of the endothelial nitric oxide synthase gene and smoking on the risk of cerebral stroke].

Violations of the endothelium-dependent regulation of cerebral vessel tone are an important link in the pathogenesis of cerebrovascular disorders. The purpose of this study was to investigate the association of--86T>C and E298D polymorphisms of the endothelial nitric oxide synthase(NOS3) gene with the risk of ce-ebral stroke (CS) in Russian inhabitants of Central Russia, as well as to evaluate the trigger effect of smoking on the risk of CS in carriers of genotypes NOS3. Genotyping of-786T>C and E298D polymorphisms of the NOS3 gene was carried out through real time. CR and TaqMan allele discrimination assays. It was deter-ined that the genotype 298DD is associated with the risk of CS (OR =-1.71, 95% CII= 1.05-2.78, P= 0.03). Subsequent analysis showed that genotype 298 DD (OR = 3.75; 95% CII= 1.39-10.11; P= 0.01) is associatedw ith an increased risk of CS exclusively in smoking individuals. The combination ofg enotypes -786T/Cx298D/D was associated with the risk of CS. n smokers (OR = 7.71; 95% CI = 1.31-45.34; P = 0.02). In the present study, it was found that smoking is a significant modifying risk factor for cerebral stroke in the carriers of the 298DD and -786T/C. enotypes of endothelial nitric oxide synthase.

[The association study of the promoter polymorphism -308G>A of tumor necrosis factor gene with the development and severity of acute pancreatitis in Russian population of Kursk region].

The aim of this study was to investigate the relationship between the polymorphism -308G>A of tumor necrosis factor (TNF) gene and the risk and severity of acute pancreatitis (AP) in unrelated Russians from Kursk region. DNA samples were obtained from 190 AP patients and 217 healthy controls for genotyping the polymorphism through a TaqMan allelic discrimination assay. Although -308G>A genotypes did not show a significant association with disease risk, the genotype -308GA was found to be associated only with non-severe type of acute alcohol-related pancreatitis (odds ratio 1.81 (95% CI 1.02-3.23 p=0.04).

[Polymorphism Gly460Trp of alpha-adducin gene and predisposition to essential hypertension. The role of gene-environment interactions in the development of the disease in Russian population].

In this study we for the first time in Russian population elucidated association between G460W polymorphism of -adducin gene (ADD1) and risk of development of hypertensive disease (HD). DNA samples from 205 patients with HD and 207 healthy nonrelated individuals of Russian nationality were genotyped for G460W polymorphism of ADD1 gene by polymerase chain reaction and restriction analysis. We detected no statistically significant differences between groups of healthy people and patients with HD. But among smokers with 460GW genotype of ADD1 gene we found elevated risk of HD development (OR 2.71, 95%CI 1.01-7.26; p=0.04). Among nonsmokers the given genotype did not influence risk of origination of the disease (OR 0.67, 95%CI 0.39-1.15; p=0.15). Moreover carriers of 460GW genotype who did not consume fresh vegetables and fruits or consumed them insufficiently (once a day or less) had the highest risk of HD development (OR 2.24, 95%CI 1.06-4.73; p=0.03) while in subjects who consumed fresh vegetables and fruits regularly the given genotype possessed protective properties in relation to risk of development of the disease (OR 0.25, 95%CI 0.09-0.68; p=0.005). Thus in the studied Russian population G460W polymorphism of ADD1 gene can be considered as predisposition gene to HD, but its pathological effect is manifested solely under influence of environmental factors.

[A protective effect of GLY272SER polymorphism of GNB3 gene in development of essential hypertension and its relations with environmental hypertension risk factors].

AIM: To study associations of C825T (rs5443) and G272S (rs16932941) polymorphisms of GNB3 gene in Russian population of the Central Chernozem region with essential hypertension (EH) risk; to elicit the role of environmental risk factors in realization of EH predisposition in this gene genotypes carriers. MATERIAL AND METHODS: We studied DNA samples obtained from 205 EH patients and 207 healthy individuals. EH patients were treated in Kursk hospitals. Genotyping of GNB3 gene polymorphisms was conducted by polymerase chain reaction and restriction analysis. RESULTS: Prevalence of 82ST allele of GNB3 gene in EH patients and healthy individual was 0.334 and 0.295, respectively, of 272S allele--0.037 and 0.058, respectively. We found no significant differences by prevalence of genotypes of gene GNB3 polymorphisms C825T and G272S in EH patients and healthy individuals. Non-smoking carriers of 272GS genotype had a low risk of EH (OR 0.42 in 95% CI from 0.18 to 0.97; p = 0.04). Smokers had no protective effect of this genotype. The protective effect of 272GS genotype was also found in individuals with low or moderate alcohol drinking habits (OR 0.29 in 95% CI from 0.11 to 0.77, p = 0.02) and in individuals without chronic exposure to stress (OR 0.29 in 95% CI from 0.09 to 0.91, p = 0.04). In contrast, hard drinkers and patients exposed to chronic stress had no protective effect of heterozygous genotype 272GS of gene GNB3. CONCLUSION: G272S polymorphism of GNB3 gene can be considered as a new genetic marker of predisposition to EH. The protective effect depends of environmental factors associated with high risk to develop EH.

[Influence of three point mutations in TNF-alpha promoter gene in clinical manifestations and complications of stomach and duodenal ulcer].

The purpose of our study was to investigate whether polymorphisms -238G/A, -308G/A, and -863C/A within the promoter of the TNF-alpha gene are associated with clinical features of gastric and duodenal ulcer disease in a Russian population. DNA samples of 381 unrelated patients with gastric and duodenal ulcer disease and 216 sex- and age-matched healthy controls were used to determine the TNF-alpha gene polymorphisms by PCR-RFLP assay. Logistic regression analysis has revealed significant associations of polymorphism -308G/A with size of ulcerous defect (p=0.03) and intestinal dyspepsia (p=0.05), polymorphism -238G/A with gastric dyspepsia (p=0.04) and reflux-esophagitis (p=0.05), polymorphism -863C/A with perforation of ulcer (p=0.04). The study results highlight impact of the TNF-alpha gene polymorphisms on various clinical features in patients with peptic ulcer disease.

[Polymorphism -930A > G of the cytochrome b gene is a novel genetic marker of predisposition to bronchial asthma].

AIM: To evaluate the link between promotional polymorphism -930A > G of the cytochrome b gene (CYBA) and onset of bronchial asthma; to examine effects of this locus on the risk of the disease development depending on the pro- and antioxidant action of environmental factors. MATERIAL AND METHODS: We studied samples of DNA obtained from 214 healthy individuals and 215 patients with bronchial asthma treated in Regional Kursk Hospital. We used polymerase chain reaction and analysed polymorphism of restriction fragments lengths for genotyping of -930A > G polymorphism of CYBA gene. RESULTS: Incidence of a variant allele -930G of CYBA gene among men with nonallergic bronchial asthma (nBA) was higher than in healthy men (OR 1.95; CI 1.02-3.73; p = 0.04). The homozygous variant genotype -930G/G was associated with a high risk of nBA in males (OR 2.66; CI 1.14-6.20; p = 0.02). In healthy individuals polymorphisms -930A > G and 640A > G were in negative linkage equilibrium (D = -0.057; p < 0.001) while in patients such associations were not registered. Male smokers with genotype -930G/G had the highest risk of nBA (OR 2.86; CI 1.06-7.77; p = 0.04) while non-smokers with this genotype had no risk of the disease (OR 1.50; CI 0.11-19.64; p = 0.70). Males with -930G/G on low or no vegetable diet had the highest risk of nBA (OR 3.11; CI 1.01-9.63; p = 0.04) while regular vegetable eaters had no risk to develop nBA (OR 0.73; CI 0.30-1.82; p = 0.50). CONCLUSION: We were the first to find relations between -930A > G polymorphism of CYBA gene and predisposition to nBA. This association exists in males and depends on the smoking status and vegetable diet.

Tobacco smoking, fruit and vegetable intake modify association between -21A>T polymorphism of catalase gene and risk of bronchial asthma.

Although oxidative stress is a cardinal feature of bronchial asthma, the role of interactions between environmental oxidant/antioxidant exposures and antioxidant genes in asthma aetiology has yet to be determined. The present study was conducted to investigate whether two common polymorphisms -21A > T and -262C > T of catalase (CAT) gene are associated with susceptibility to asthma in a Russian population and to test the hypothesis that the asthma risk attributed to CAT genotypes could be dependent on both oxidant (tobacco smoking) and antioxidant (fruit and vegetable intake) exposures. A total of 429 unrelated Russian individuals from Central Russia were recruited in the study, including 215 asthmatics and 214 sex- and age-matched healthy controls. Genotyping analysis for the CAT gene polymorphisms was performed by PCR-RFLP assays. The frequencies of both allele -21A (OR 0.73 95%CI 0.55-0.96 p = 0.03) and -21AA CAT genotype (OR 0.42 95%CI 0.23-0.76 p = 0.004) were higher among asthmatics than among healthy controls. The frequency of -21AA genotype of the CAT gene was significantly higher in patients with allergic (OR 0.47 95%CI 0.25-0.92 p = 0.024) and nonallergic (OR 0.32 95%CI 0.14-0.71 p = 0.004) asthma in comparison with controls (at the Bonferroni corrected p value less than 0.025). Polymorphisms -21A > T and -262C > T of the catalase gene were in a positive linkage disequilibrium (p < 0.0001). Smokers who carried -21AA genotype had an increased risk of nonallergic asthma (p = 0.002), whereas nonsmoker carriers of this genotype did not have the risk of any variant of the disease. Notably, no association of CAT genotype -21AA with asthma was found in high fruit and vegetable consumers, whereas low fruit and vegetable consumers (one time per day or less often) possessing this genotype were at increased risk of both allergic (p = 0.013) and nonallergic (p = 0.008) asthma. This is the first study reporting an association of polymorphism -21A > T of the catalase gene with allergic and nonallergic asthma. We also found, for the first time, that cigarette smoking and fruit and vegetable intakes have potentially inverse modifying influences on the asthma risk in individuals with -21AA CAT genotype and that the gene-environment interactions that were found support the biologic plausibility of catalase gene for the development of bronchial asthma.

The relationship between polymorphisms in the glutamate cysteine ligase gene and asthma susceptibility.

The present study was designed to investigate an association of common -588C/T and -23G/T polymorphisms within glutamate cysteine ligase modifier subunit gene with susceptibility to bronchial asthma. A total of 435 ethnically Russian subjects were recruited in this study, including 221 patients with asthma and 214 sex and age matched healthy subjects. As previously reported, the -588C/T and -23G/T polymorphisms were completely linked. The -588TT/-23TT genotype was found to be associated with decreased risk of allergic asthma after adjustment for age, gender and smoking status using multivariate logistic regression analysis (OR=0.33 95% CI 0.15-0.70, p=0.036). However, the -588CT/-23GT genotype was associated with increased risk of non-allergic asthma (OR=2.03 95% CI 1.05-3.90, p=0.06). This is a first study reporting the association between genetic variations in the glutamate cysteine ligase gene and susceptibility to bronchial asthma.

[Heterozygosity of 198LEU mutant allele in glutathione peroxidase-1 gene as a risk factor of bronchial asthma associated with smoking].

AIM: To investigate whether smoking has a differential effect by Pro198Leu genotypes of the glutathione peroxidase-1 (GPx1) gene on the risk of bronchial asthma (BA) in Russian population. MATERIAL AND METHODS: DNA samples from 195 asthmatics and 167 healthy volunteers were genotyped for Pro198Leu polymorphism of the GPx1 gene by polymerase chain reaction and restriction fragment length analysis. RESULTS: Smoking was significantly associated with an increased risk of non-allergic BA in males but not in females (p < 0.00001). When smoking was examined according to Prol98Leu polymorphism of the GPx1 gene, association of 198Pro/Leu genotype with susceptibility to allergic BA was found only in male smokers (odds ratio = 2.51, 95% confidence interval = 1.04 to 6.06, p = 0.04). CONCLUSION: The risk of allergic BA associated with smoking is increased in males who are heterozygous carriers for the low-activity 198Leu allele of the glutathione peroxidase-1 gene. The importance of molecular mechanisms is shown by which functional variants of antioxidant defense genes may mediate potentially oxidative effects of tobacco smoke on asthmatic phenotype.

[Genetic-demographic structure and prevalence of congenital malformations in rural regions of the Kursk district]. / Genetiko-demograficheskaia struktura i rasprostrannost' vrozhdennykh porokov razvitiia v sel'skikh raionakh Kurskoi oblasti.

Investigation of the the genetics, demography, and epidemiology of congenital malformations (CMs) in Kursk oblast revealed statistically significant correlations between population parameters and the incidence of CM in the rural rations of the oblast. The general prevalence of CM and that of the separate CM forms ("guard" CM, multiple CM, hemangioma, congenital heart disease, congenital myelocele, talipes valgus, congenital femoral luxation, polydactyly, cryptorchism) increased with an increase in the average marital age of men and women of the reproductive part of the population and with an increase in the level of the populations homozygosity (an increase in the local consanguinity and ethnic marriage assortativeness, a decrease in the populations's migration activity, an increase in the proportion of genotypes homozygous for recessive genes, etc).