Effects of intranasal Imunofan administration upon phagocytic activity in treatment of exudative otitis media in children

Exudative otitis  media  in  childhood is most  often  associated with  chronic inflammation in the  nasopharyngeal area,  with  immediate participation of phagocytic cells. Our  paper  presents  the  data  on evaluation of clinical  and immunological efficacy of intranasal Imunofan use included into  complex therapy of exudative  otitis  media.  Dynamic observation (before  treatment, 1 and  3 months after treatment) of these parameters included regular  evaluation of the  neutrophil and  monocyte amounts in peripheral blood  and  in smear imprints from nasal mucosa, determination of myeloperoxidase activity in circulating neutrophils, and the content of interleukin IL-8 and IL-18  in the nasal washouts. The clinical status was assessed using a scoring system, which subjectively reflected the state of the nasopharynx and auditory function. Fourty-three children aged from 3 to 7 years with exudative  otitis media associated with chronic adenoiditis were examined. Patients of the first group (22 children) were treated using only conventional approaches (basic therapy). The patients from  the  second  group  (21 children) received  Imunofan in addition to the  basic therapy. The  control group consisted of 16 relatively  healthy  children. Before  treatment of the  children with exudative  otitis  media, an increase  in the relative content of monocytes in their blood,  a decreased activity of myeloperoxidase and lower concentration of IL-8  and  IL-18  in the  nasal  wash was observed  in comparison with  healthy  controls. No differences in severity  of clinical  symptoms were revealed  between  the  groups  of patients. Baseline  therapy was not  accompanied by positive  dynamics in the  clinical  pattern of the  disease.  Relative  monocytosis and reduced activity of neutrophilic myeloperoxidase persisted  in peripheral blood;  the concentration of IL-8  and IL-18  in the  nasal washings  remained low. Following intranasal use of Imunofan, the  number of circulating monocytes was restored by the  third  month from  the  start  of treatment, there  was an  increased activity  of myeloperoxidase registered  in blood neutrophils, as well as higher IL-8  and IL-18  concentrations in the nasal washings. Normalization of the phagocytos-related parameters, according to this scoring,  was associated with clinical remission of the disease. The revealed relationships between clinical data and the results obtained in the course  of laboratory research  suggest a positive effect of Imunofan as an agent that may enhance effectiveness of conventional basic therapy  of otitis media in children

Подходы к разработке индивидуализированных схем лечения экссудативного среднего отита у пациентов с низкой эффективностью традиционной консервативной терапии

Management of otitis media with effusion is a challenging problem in view of its high prevalence and frequent complications in the form of stable hearing loss. High frequency of secondary immunodeficiencies in ENT diseases dictates the necessity of immunocorrection in combined treatment. Dinamic pure tone audiometry, tympanometry and subjective response demonstrated higher treatment efficiency in the «Gepon» groups.Актуальность проблемы экссудативного среднего отита объясняется его распространенностью и частотой развития стойкой тугоухости. Высокая частота вторичных иммунодефицитов при ЛОР-патологии диктует необходимость иммунокоррекции в их комплексном лечении. Динамическая тональная аудиометрия, тимпанометрия, а также субъективные данные выявили более высокие результаты лечения у больных, получавших транстимпанальное введение иммуномодулирующего препарата «Гепон»

Genetic Variation in OAS1 Is a Risk Factor for Initial Infection with West Nile Virus in Man

West Nile virus (WNV) is a re-emerging pathogen that can cause fatal encephalitis. In mice, susceptibility to WNV has been reported to result from a single point mutation in oas1b, which encodes 2′–5′ oligoadenylate synthetase 1b, a member of the type I interferon-regulated OAS gene family involved in viral RNA degradation. In man, the human ortholog of oas1b appears to be OAS1. The ‘A’ allele at SNP rs10774671 of OAS1 has previously been shown to alter splicing of OAS1 and to be associated with reduced OAS activity in PBMCs. Here we show that the frequency of this hypofunctional allele is increased in both symptomatic and asymptomatic WNV seroconverters (Caucasians from five US centers; total n = 501; OR = 1.6 [95% CI 1.2–2.0], P = 0.0002 in a recessive genetic model). We then directly tested the effect of this SNP on viral replication in a novel ex vivo model of WNV infection in primary human lymphoid tissue. Virus accumulation varied markedly among donors, and was highest for individuals homozygous for the ‘A’ allele (P<0.0001). Together, these data identify OAS1 SNP rs10774671 as a host genetic risk factor for initial infection with WNV in humans

Coronavirus Gene 7 Counteracts Host Defenses and Modulates Virus Virulence

Transmissible gastroenteritis virus (TGEV) genome contains three accessory genes: 3a, 3b and 7. Gene 7 is only present in members of coronavirus genus a1, and encodes a hydrophobic protein of 78 aa. To study gene 7 function, a recombinant TGEV virus lacking gene 7 was engineered (rTGEV-Δ7). Both the mutant and the parental (rTGEV-wt) viruses showed the same growth and viral RNA accumulation kinetics in tissue cultures. Nevertheless, cells infected with rTGEV-Δ7 virus showed an increased cytopathic effect caused by an enhanced apoptosis mediated by caspase activation. Macromolecular synthesis analysis showed that rTGEV-Δ7 virus infection led to host translational shut-off and increased cellular RNA degradation compared with rTGEV-wt infection. An increase of eukaryotic translation initiation factor 2 (eIF2α) phosphorylation and an enhanced nuclease, most likely RNase L, activity were observed in rTGEV-Δ7 virus infected cells. These results suggested that the removal of gene 7 promoted an intensified dsRNA-activated host antiviral response. In protein 7 a conserved sequence motif that potentially mediates binding to protein phosphatase 1 catalytic subunit (PP1c), a key regulator of the cell antiviral defenses, was identified. We postulated that TGEV protein 7 may counteract host antiviral response by its association with PP1c. In fact, pull-down assays demonstrated the interaction between TGEV protein 7, but not a protein 7 mutant lacking PP1c binding motif, with PP1. Moreover, the interaction between protein 7 and PP1 was required, during the infection, for eIF2α dephosphorylation and inhibition of cell RNA degradation. Inoculation of newborn piglets with rTGEV-Δ7 and rTGEV-wt viruses showed that rTGEV-Δ7 virus presented accelerated growth kinetics and pathology compared with the parental virus. Overall, the results indicated that gene 7 counteracted host cell defenses, and modified TGEV persistence increasing TGEV survival. Therefore, the acquisition of gene 7 by the TGEV genome most likely has provided a selective advantage to the virus

Approaches to the development of individualized schemes for treatment of otitis media with effusion in patients with low efficiency of traditional conservative therapy

Management of otitis media with effusion is a challenging problem in view of its high prevalence and frequent complications in the form of stable hearing loss. High frequency of secondary immunodeficiencies in ENT diseases dictates the necessity of immunocorrection in combined treatment. Dinamic pure tone audiometry, tympanometry and subjective response demonstrated higher treatment efficiency in the «Gepon» groups

IMMUNOLOGIC RISK FACTORS OF DEVELOPMENT OTITIS MEDIA WITH EFFUSION IN CHILDREN SUFFERING FROM CHRONIC ADENOIDITIS

There were 24 patients with chronic adenoiditis in the 1st group, another 24 patients with chronic adenoiditis in association with otitis media effusion (OME) were included in the 2d group. The study of mucosal immunity included assessment of SIgA, IL-6, IFN- and IL-10 levels in nasal washes. Decrease of SIgA content and increase of the number of IFN-γ-positive samples was revealed in children from the 2nd clinical group, which allows to regard these characteristics of the mucosal immunity as the risk factors for the development of otitis media with effusion