Ludmila M. Ogorodova

Opisthorchis felineus and Metorchis bilis are the main agents of liver fluke infection of humans in Russia.

Liver fluke infections are gradually transforming from a local problem of individual geographic regions to a widespread problem. The observed expansion is likely to be connected with the ever-increasing intensity of traffic flow and migration of the infected carriers between cities, regions, and countries. Opisthorchis felineus, the trematode belonging to the family Opisthorchiidae, is a well known causative agent of the infection called opisthorchiasis. Metorchis bilis, also a member of the family Opisthorchiidae, causes metorchiasis, a disease very close to opisthorchiasis in symptomatology. Genetic markers can be used to develop methods for differential diagnostics of these diseases. However, the questions connected with epidemiology of these trematode infections, their clinical characteristics, prognosis and therapy remain open. This review briefs the general biological characteristics of O. felineus and M. bilis persisting in various countries of Eurasia, their geographical range, epidemiology and molecular diagnostics of these liver flukes.

Salmeterol/fluticasone propionate vs. double dose fluticasone propionate on lung function and asthma control in children

There is a large body of data to support the use of an inhaled corticosteroid (ICS) plus a long‐acting β2‐agonist vs. increasing the dose of ICS in adults, but less data in children. This double‐blind, parallel group, non‐inferiority study compared lung function and asthma control, based on Global Initiative for Asthma guidelines, in children receiving either salmeterol/fluticasone propionate (SFC) 50/100 μg bd (n = 160) or fluticasone propionate (FP) 200 μg bd (n = 161) for 12 wks. Change from baseline in mean morning peak expiratory flow increased following both treatments, but was significantly greater in the SFC group compared with FP [Adjusted mean change (s.e.) (l/min): SFC: 26.9 (2.13), FP: 19.3 (2.12); treatment difference: 7.6 (3.01); 95% CI: 1.7, 13.5; p = 0.012)]. Asthma control improved over time in both groups. Mean pre‐bronchodilator maximal‐expiratory flow at 50% vital capacity and percentage rescue‐free days showed significantly greater improvements in the SFC group compared with FP. All other efficacy indices showed comparable improvements in each group. Treatment with SFC 50/100 μg bd compared with twice the steroid dose of FP (200 μg bd), was at least as effective in improving individual clinical outcomes and overall asthma control, in asthmatic children previously uncontrolled on low doses of ICS.

Opisthorchiasis: an overlooked danger

1 Siberian State Medical University, Tomsk, Russian Federation, 2 Tropical Disease Research Laboratory, Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, 3 Laboratory of Molecular Mechanisms of Pathological Processes, Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation, 4 Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland, 5 University of Basel, Basel, Switzerland, 6 Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland, 7 Department of Microbiology, Immunology and Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, GeorgeWashington University, Washington, D.C., United States of America, 8 Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands, 9 Department of Chemistry, Tomsk State University, Tomsk, Russian Federation, 10 Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany, 11 Academic Division of Thoracic Surgery, Royal Brompton Hospital, London, United Kingdom, 12 Population Genetics Laboratory, Research Institute for Medical Genetics, Siberian Branch of Russian Academy of Medical Sciences, Tomsk, Russian Federation, 13 Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russian Federation, 14 ReMedys Foundation, Geneva, Switzerland, 15 External R&D Innovation, Pfizer Russia, Moscow, Russian Federation, 16 Department of Parasitology and Leiden Parasite Immunology Group, Leiden University Medical Center, Leiden, the Netherlands

Investigation of the interaction between DNA and cobalt ferrite nanoparticles by FTIR spectroscopy

AbstratctThe interaction of DNA with nanoparticles of cobalt ferrite powder prepared by the mechano-chemical method was studied. It was shown that CoFe2O4 nanoparticles efficiently bind DNA in aqueous solutions (Tris-HCl), forming a bionanocomposite. The adsorption capacity of CoFe2O4 nanoparticles for DNA was evaluated to be 5.25 × 10−3 mol/m2. The desorption of DNA from the surface of the particles was analyzed while changing the pH, the ionic strength, and the chemical content of the medium. The DNA-CoFe2O4 nanocomposite was investigated by FTIR spectroscopy. The block of the data allowed one to consider the mechanism of the interaction between a polynucleotide and CoFe2O4 nanoparticles and to make the assumption that the binding occurred due to the coordination interaction of the phosphate groups and heterocyclic bases of DNA (oxygen atoms of thymine and guanine) with metal ions on the particle surface. The analysis of the IR spectra showed that binding can lead to the partial destabilization of the DNA structure, with the B conformation of a polynucleotide being preserved.

Morphological and Molecular Characteristics of “Difficult” Asthma

Background. There are several clinical variants of severe difficult-to-treat asthma: asthma with persistent airflow limitation, brittle asthma, and fatal asthma; but the differences between the pathogenetic mechanisms underlying the disease heterogeneity are unknown. Objectives. The aim was to evaluate the morphological and molecular characteristics of brittle asthma type I and asthma with persistent airflow limitation compared to mild-to-moderate asthma, by the analysis of the cellular structure and gene expression in the bronchial mucosa. Methods. Bronchoscopic evaluation was performed in 42 asthmatic patients: 10 with brittle asthma, 10 with severe asthma with persistent airflow limitation, and 22 with mild-to-moderate asthma. Morphometric and cytological analyses of the bronchial mucosa were performed. The mRNA levels for the ADRB2, HRH1, and CHRM3 genes in the bronchial mucosa were measured by quantitative real-time polymerase chain reaction (PCR). Results. A predominance of eosinophils (29.48/mm2, 95% confidence interval [CI] 25.24–33.72) and neutrophils (40.13/mm2, 95% CI 32.77–47.49) was observed in patients with mild-to-moderate asthma; however, histiocytes-macrophages (65.80/mm2, 95% CI 56.95–74.65) and lymphocytes (52.94/mm2, 95% CI 42.83–63.06) were more common in patients with brittle asthma, and neutrophil counts (81.11/mm2, 95% CI 58.33–103.89) were significantly increased in subjects with persistent airflow limitation. An increase in the expression of the M3-cholinoreceptor and the β2-adrenoreceptor genes was demonstrated in severe asthmatics compared to mild-to-moderate asthma patients. Significantly higher levels of CHRM3 (57.17%, 95% CI 55.04–59.29) and HRH1 (38.82%, 95% CI 35.84–41.81) mRNAs were observed in patients with brittle asthma. The level of ADRB2 gene expression (71.41%, 95% CI 63.54–85.09) was maximal in patients with asthma with persistent airflow limitation. Conclusions. There is evidence of significantly different morphological characteristics and molecular mechanisms of inflammation and bronchoconstriction underlying the clinical heterogeneity of severe asthma.

Association of polymorphisms in the human IL4 and IL5 genes with atopic bronchial asthma and severity of the disease

Two polymorphisms in the IL4 (G/C 3′-UTR) and IL5 (C-703T) genes were studied in a sample of families whose probands had atopic bronchial asthma (BA) (66 families, n = 183) and in a group of non-cognate individuals with the severe form of the disease (n = 34). The samples were collected from the Russian population in the city of Tomsk (Russia). Using the transmission/disequilibrium test (TDT), a significant association of allele C-703 IL5 with BA was established (TDT = 4.923, p = 0.007 ± 0.0007). The analysis of 40 individuals with mild asthma and 49 patients with the severe form of the disease revealed a negative association of genotype GG IL4 (OR = 0.39, 95% CI = 0.15−0.99, p = 0.035), and also a trend towards a positive association of the GC IL4 genotype (OR = 2.52, 95% CI = 0.98−6.57, p = 0.052) with mild BA. There was a concordance of the clinical classification of BA severity with the ‘genotype’ (McNemar’s χ2 test with continuity correction constituted 0.03, d.f. = 1, p = 0.859). These results suggest that polymorphisms in the IL4 and IL5 genes contribute to the susceptibility to atopic BA and could determine the clinical course of the disease.

Polymorphism of the glutathione S-transferase genes (GSTT1, GSTM1) in west Siberian patients with atopic bronchial asthma

Polymorphism for the GSTT1 and GSTM1 null alleles was analyzed in 69 patients with atopic bronchial asthma (BA) and in 57 healthy individuals from Tomsk. The two samples did not differ in frequencies of genotypes 0/0 and + of either gene or in frequencies of genotype combinations. No association was observed for GST and BA severity. Thus, the GST null alleles proved to be unimportant for BA.

Opisthorchis felineus infection and cholangiocarcinoma in the Russian Federation: a review of medical statistics

Opisthorchis felineus (O. felineus) occurs in Western Siberia and many other parts of the Russian Federation (RF). The true extent of its distribution is not known. Chronic infection may lead to severe hepatobiliary morbidity. According to surgical and experimental reports, long-term infestation might significantly increase the risk for cholangiocarcinoma (CCA). To date, no association between O. felineus infection and CCA has been demonstrated. The objective of this study was to review existing health data on the incidence of O. felineus infection and on the incidence of CCA in the RF. We reviewed the official medical statistics on reported O. felineus infection and CCA in 83 political/geographical units of the RF, covering the period January 2011-December 2013. Annual incidence data were obtained from Rospotrebnadzor and from official medical statistics. We calculated the average annual incidence of infection and cancer. The average annual incidence of O. felineus was 24.7±9.0 cases per 100,000 population. The highest incidence was observed in Khanty-Mansiysk district (599.7 cases per 100,000 population per year). In 27 geographical units, no O. felineus cases were reported. The incidence of liver and intrahepatic bile duct cancers was 4.8±0.2 cases per 100,000 population; the highest rate was reported in Sakha Republic and Tomsk Oblast (14.5 and 9.3 cases per 100,000 population), and the lowest in Yamalo-Nenets Autonomous Okrug (0.9 cases per 100,000 population). O. felineus incidence was not associated with the mean annual incidence of liver and intrahepatic bile duct cancers (r=0.20, p=0.07). This study documents the importance of opisthorchiasis in certain endemic areas and presents the best available data on associations between O. felineus infection and liver/intrahepatic bile duct cancers in RF. The findings support the need to implement a public health control programme against liver fluke infections and to increase the availability of anthelmintic treatment. Further studies are warranted to assess the contribution of opisthorchiasis to the CCA in RF.

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.

The association between foodborne and orofecal pathogens and allergic sensitisation - EuroPrevall study

An inverse association between markers of exposure to foodborne and orofecal pathogens and allergic sensitization has been reported. However, the findings of epidemiological studies have not been consistent. This study investigated the relationship between antibodies to hepatitis A, Toxoplasma gondii and salmonella and allergic sensitization to food and aeroallergens in children from different geographical areas.