[Pharmacological prevention of fibrosis in dacryosurgery]. / Medikamentoznaya profilaktika fibrotizatsii v dakriokhirurgii.

Chronic inflammatory process in the lacrimal drainage system is the main etiological factor leading to dacryostenosis and consequent obliteration - partial and total nasolacrimal duct obstruction. Prevention of this process is an urgent problem in dacryology. Currently, there is very little research on the development and use of conservative methods for treating dacryostenosis using anti-inflammatory, as well as anti-fibrotic drugs. In this regard, the main method of treating lacrimal drainage obstruction is dacryocystorhinostomy. However, the problem of recurrence after this operation has not been resolved. The causes of recurrence can be cicatricial healing of dacryocystorhinostomy ostium, canalicular obstruction, formation of granulations and synechiae in its area. Surgical methods of recurrence prevention are associated with possible complications, and there is conflicting data on the feasibility of their use. Based on this, the development of pharmacological methods for the prevention of fibrosis in dacryology is promising, among which the antitumor antibiotic Mitomycin C is the most studied. However, there are no specific scientifically substantiated recommendations for the use of this drug, and the data on its effectiveness vary. This has prompted researchers to look for and study alternative anti-fibrotic agents, such as antitumor drugs, glucocorticoids, hyaluronic acid, small molecule, biological, immunological and genetically engineered drugs, as well as nanoparticles. This review presents the current data on the efficacy and prospects of the use of these drugs in dacryology.

The epidemiological status of African swine fever in domestic swine herds in the Tavush Province region, Armenia.

KEEN The factors associated with the spread and persistence of African swine fever (ASF) in the Caucasus region remain to be fully identified. It is assumed that large naive populations of domestic free-ranging and wild pigs are critical to disease transmission and maintenance. Nonetheless, 11 years since its epidemic introduction into the region in 2007, ASF virus (ASFV) is still circulating, suggesting that an endemic cycle has been established based on contact between free-ranging domestic pigs and wild pigs, and that native Ornithodoros ticks probably serve as reservoirs for the virus. Therefore, research is required to gather information on the epidemiological status of ASF in the Caucasus region, focusing particularly on understanding modes of ASFV spread and persistence in this new virus environment. The authors established an ASFV survey targeting domestic pigs in the Tavush province of northern Armenia, an area of the country considered to be at high risk of disease incursion/occurrence. All tested samples collected for this survey were negative for ASF. The probability of observing no reactors by antibody enzyme-linked immunosorbent assay in a sample of this size (n = 1,506) from a population with an estimated disease prevalence of 1% is very low (< 0.0001). Therefore, it is possible but very unlikely for ASFV to be present among domestic pigs in the Tavush province region.

Les facteurs associés à la propagation de la peste porcine africaine (PPA) dans le Caucase et à sa persistance restent en grande partie à élucider. On suppose que la présence de populations naïves de porcs domestiques en liberté et de porcs sauvages joue un rôle déterminant dans la transmission et le maintien de la maladie. Néanmoins, 11 ans après son introduction épidémique dans la région en 2007, le virus de la peste porcine africaine (VPPA) est toujours présent, ce qui laisse penser qu'un cycle s'est installé à la faveur des contacts entre les porcs domestiques en liberté et les porcs sauvages, les tiques autochtones Ornithodoros faisant probablement office de réservoir viral. Des études sont donc nécessaires pour recueillir des informations sur le statut épidémiologique de la PPA dans le Caucase et plus particulièrement pour comprendre les modalités de la propagation et de la persistance du VPPA dans ce nouvel environnement. Les auteurs rapportent les résultats d'une enquête épidémiologique sur le VPPA conduite chez les porcs domestiques de la province du Tavush, au nord de l'Arménie, zone considérée comme présentant un risque élevé d'incursion et d'émergence de la maladie. Les échantillons prélevés à cette fin ont tous donné des résultats négatifs au test de détection de la PPA. La probabilité qu'un échantillon de cette taille (n = 1 506) ne donne aucune réaction positive à l'épreuve ELISA de détection d'anticorps dans une population pour laquelle la prévalence de la maladie est estimée à 1 % est extrêmement faible (< 0,0001). On peut en conclure que la présence du VPPA parmi les porcs domestiques de la région du Tavush est possible, mais très improbable.

Aún no están perfectamente identificados los factores que intervienen en la propagación y persistencia de la peste porcina africana (PPA) en la región del Cáucaso. Se presupone que la existencia de grandes poblaciones de cerdos salvajes y cerdos domésticos en libertad que no han estado expuestas previamente al patógeno es un factor crucial en la transmisión y el mantenimiento de la enfermedad. Sin embargo, 11 años después de su penetración epidémica en la región, en 2007, el virus de la PPA aún sigue en circulación, hecho que parece apuntar al establecimiento de un ciclo endémico mediado por el contacto entre cerdos domésticos en libertad y cerdos salvajes y también a la probable función de la garrapata autóctona Ornithodoros como reservorio del virus. Por consiguiente, es necesario investigar para reunir información sobre la situación epidemiológica de la PPA en la región del Cáucaso, procurando especialmente aprehender las modalidades de propagación y persistencia del virus en este nuevo entorno. Los autores estudiaron la presencia del virus de la PPA específicamente en cerdos domésticos de la provincia de Tavush, al norte de Armenia, una zona del país considerada muy expuesta al riesgo de incursión o manifestación de la enfermedad. Todas las muestras obtenidas y analizadas para el estudio dieron resultado negativo a la PPA. La probabilidad de no detectar con ELISA ningún ejemplar con anticuerpos en una muestra de tal tamaño (n = 1 506), tomada de una población con una prevalencia de la enfermedad que según los cálculos es del 1%, resulta ínfima (<0,0001). Es por lo tanto posible, pero harto improbable, que el virus de la PPA esté presente en los cerdos domésticos de la zona de la provincia de Tavush.

Prenatal allergen exposures prevent allergen-induced sensitization and airway inflammation in young mice.

BACKGROUND: Immune-modulation such as tolerance induction appears to be an upcoming concept to prevent development of atopic diseases. Pregnancy might present a critical period for preventing allergic sensitization of the progeny. We investigated the effect of maternal allergen exposures during pregnancy on allergen-induced sensitization and airway inflammation in the offspring in a murine model. METHODS: BALB/c mice were exposed to aerosolized ovalbumin (OVA) three times per week from day 7 of pregnancy until delivery (day 0). Offspring were systemically sensitized by six intraperitoneal injections with OVA between postnatal days 21 and 35, prior to airway allergen challenges on days 48, 49, and 50. Analyses were performed on day 52. To examine long-lasting effects of maternal OVA exposures some offspring were sensitized between days 115 and 129; analyses took place on day 147. RESULTS: Compared to maternal placebo exposures, maternal OVA exposures suppressed OVA-specific IgE serum levels and inhibited development of allergen-induced airway inflammation in the OVA-sensitized offspring on both days 52 and 147. This protective effect was associated with a shift from a predominant Th2 immune response toward a predominant production of the cytokines IFN-γ and IL-10. Further, maternal OVA exposures were associated with development of CD25(+) Foxp3(+) regulatory T cells (T(regs)) in the OVA-sensitized offspring. Depletion of T(regs) or neutralization of IL-10 prior to allergen sensitization re-established OVA-induced sensitization and eosinophilic airway inflammation in the OVA-sensitized offspring. CONCLUSIONS: In our model, maternal allergen exposures during pregnancy prevented later allergen-mediated sensitization and airway inflammation by allergen-specific tolerance induction in the offspring.

Lipocalin2 protects against airway inflammation and hyperresponsiveness in a murine model of allergic airway disease.

BACKGROUND: Allergen-induced bronchial asthma is a chronic airway disease that involves the interplay of various genes with environmental factors triggering different inflammatory pathways. OBJECTIVE: The aim of this study was to identify possible mediators of airway inflammation (AI) in a model of allergic AI via microarray comparisons and to analyse one of these mediators, Lipocalin2 (Lcn2), for its role in a murine model of allergic airway disease. METHODS: Gene microarrays were used to identify genes with at least a twofold increase in gene expression in the lungs of two separate mouse strains with high and low allergic susceptibility, respectively. Validation of mRNA data was obtained by Western blotting, followed by functional analysis of one of the identified genes, Lcn2, in mice with targeted disruption of specific gene expression. Epithelial cell cultures were undertaken to define induction requirements and possible mechanistic basis of the results observed in the Lcn2 knock-out mice. RESULTS: Lcn2 was up-regulated upon allergen sensitization and airway challenges in lung tissues of both mouse strains and retraced on the protein level in bronchoalveolar lavage fluids. Functional relevance was assessed in mice genetically deficient for Lcn2, which showed enhanced airway resistance and increased AI associated with decreased apoptosis of lung inflammatory cells, compared with wild-type controls. Similarly, application of Lcn2-blocking antibodies before airway challenges resulted in increased inflammation and reduced apoptosis. CONCLUSION: These data indicate a protective role for Lcn2 in allergic airway disease, suggesting a pro-apoptotic effect as the underlying mechanism.

Gastrointestinal nematode infection interferes with experimental allergic airway inflammation but not atopic dermatitis.

BACKGROUND: Some helminth infections are negatively associated with the prevalence of allergic disorders, arguing for a modulation of allergic reactions by the parasites, depending on the worm species, intensity and phase of infection and the type of disease. OBJECTIVE: The aim of this study was to analyse the influence of a chronic infection with the gastrointestinal nematode Heligmosomoides polygyrus, in a murine model of allergic airway disease and of atopic dermatitis (AD), respectively. METHODS: Mice were infected with H. polygyrus and systemically sensitized with the model allergen ovalbumin. Subsequently, the animals were challenged with the allergen either via the airways for induction of airway disease, or via skin patches for induction of dermatitis. RESULTS: Mice concomitantly infected with H. polygyrus showed diminished eosinophil and lymphocyte recruitment into the lungs and decreased allergen-specific IgE levels when compared with sensitized and airway challenged controls. In addition, animals showed a trend towards reduced airway hyper-reactivity. In contrast, no significant differences in the severity of eczematous skin lesions were observed between infected and control animals in the AD model. Although H. polygyrus infection reduced CD8+ and CD4+ T-cell infiltration into the skin and production of allergen-specific IgE, mast cell recruitment was significantly increased in worm-infected mice in the dermatitis model. The worm infection was associated with significantly elevated numbers of Foxp3+ regulatory T cells (Treg) in peribronchial lymph nodes in H. polygyrus-infected sensitized and airway challenged mice. In contrast, Treg cells were basically absent in eczematous skin and their number was not increased in skin-draining lymph nodes of mice with experimental dermatitis. CONCLUSION: Infection with the gastrointestinal nematode used in our study leads to significant inhibition of mucosa-associated but not cutaneous allergic reactions, pointing to a site specificity of the immunomodulation exerted by helminths. This finding might be an important aspect for future considerations of helminths for treatment of allergic diseases.

Intranasal delivery of whole influenza vaccine prevents subsequent allergen-induced sensitization and airway hyper-reactivity in mice.

BACKGROUND: Infection with influenza virus has been associated with seemingly opposing effects on the development of asthma. However, there are no data about the effects of mucosal vaccination with inactivated influenza on the inception of allergic asthma. OBJECTIVE: To assess the immunological effects of inhaled inactivated influenza vaccine, using two different types of flu vaccines, on the inception of allergic sensitization and allergen-mediated airway disease in a mouse model. METHODS: BALB/c mice were intranasally or intratracheally vaccinated with whole or split influenza virus vaccine (days -1 or -1, 27) before systemic sensitization with ovalbumin (OVA) (days 1, 14) and repeated airway allergen challenges (days 28-30). Allergen sensitization (IgE serum levels), airway inflammation (differential cells in bronchoalveolar lavage fluid) and airway hyper-reactivity (AHR) (in vivo lung function) were analysed. RESULTS: The intranasal instillation of whole influenza vaccine before allergen sensitization significantly reduced the serum levels of total and OVA-specific IgE as well as allergen-induced AHR. Prevention was due to an allergen-specific shift from a predominant T helper (Th)2- towards a Th1-immune response. Application of split influenza vaccine did not show the same preventive effect. CONCLUSION: Intranasal administration of inactivated whole influenza vaccine reduced subsequent allergen sensitization and prevented allergen-induced AHR. Our results show that the composition of the influenza vaccine has a major influence on subsequent development of allergen-induced sensitization and AHR, and suggest that mucosal inactivated whole influenza vaccination may represent a step towards the development of a preventive strategy for atopic asthma.

Probiotic-induced suppression of allergic sensitization and airway inflammation is associated with an increase of T regulatory-dependent mechanisms in a murine model of asthma.

BACKGROUND: Microbial intestinal colonization in early in life is regarded to play a major role for the maturation of the immune system. Application of non-pathogenic probiotic bacteria during early infancy might protect from allergic disorders but underlying mechanisms have not been analysed so far. OBJECTIVE: The aim of the current study was to investigate the immune effects of oral application of probiotic bacteria on allergen-induced sensitization and development of airway inflammation and airway hyper-reactivity, cardinal features of bronchial asthma. METHODS: Newborn Balb/c mice received orally 10(9) CFU every second day either Lactobacillus rhamnosus GG or Bifidobacterium lactis (Bb-12) starting from birth for consecutive 8 weeks, during systemic sensitization (six intraperitoneal injections, days 29-40) and airway challenge (days 54-56) with ovalbumin. RESULTS: The administration of either Bb-12 or LGG suppressed all aspects of the asthmatic phenotype: airway reactivity, antigen-specific immunoglobulin E production and pulmonary eosinophilia (mean: 137 vs. 17 and 13 cellsx10(3)/mL, respectively). Antigen-specific recall proliferation by spleen cells and T-helper type 2 cytokine production (IL-4, IL-5 and IL-10) by mesenteric lymph node cells also showed significant reduction, while TGF production remained unchanged. Oral LGG administration particularly suppressed allergen-induced proliferative responses and was associated with an increase in numbers of TGF-beta-secreting CD4+/CD3+ T cells in mesenteric lymph nodes (6.5, 16.7%) as well as nearly 2-fold up-regulation of Foxp3-expressing cells in peribronchial lymph nodes. CONCLUSIONS: Neonatal application of probiotic bacteria inhibits subsequent allergic sensitization and airway disease in a murine model of asthma by induction of T regulatory cells associated with increased TGF-beta production.

Common vaccine antigens inhibit allergen-induced sensitization and airway hyperresponsiveness in a murine model.

BACKGROUND: Co-vaccination with cellular pertussis vaccine down-regulates allergic sensitization to diphtheria and tetanus antigens. Using a murine model, we investigated whether vaccination with diphtheria/tetanus toxoids, administered separately or simultaneously with the whole cell vaccine of Bordetella pertussis, inhibits subsequent allergen-induced immune and inflammatory responses. METHODS: BALB/c-mice were vaccinated intracutaneously with a combination of diphtheria and tetanus toxoids or a combination of diphtheria and tetanus toxoids with a whole cell vaccine of B. pertussis (three times, days -21 to -7) prior to systemic sensitization (days 1-14) and repeated airway challenges (days 28-30) with ovalbumin. RESULTS: Compared with negative controls, systemic sensitization and airway allergen challenges induced high serum levels of allergen-specific IgE, predominant Th2-type cytokine production, airway inflammation and development of in vivo airway hyperreactivity. Vaccination with diphtheria and tetanus toxoids prior to sensitization suppressed IgE formation and development of eosinophilic airway inflammation. Co-vaccination with a whole cell pertussis vaccine inhibited allergen sensitization, airway inflammation and development of in vivo airway hyperreactivity. Prevention was due to an allergen-specific and general shift from a predominant Th2 towards a predominant Th1 immune response. CONCLUSION: Vaccination with diphtheria and tetanus toxoids alone or in combination with whole cell pertussis vaccine prior to allergen sensitization prevented allergen-induced Th2 immune responses. Vaccine antigens may down-regulate allergic responses to a range of common allergens.

An approach for access differentiation design in medical distributed applications built on databases.

A formalized "top to bottom" design approach was described in [1] for distributed applications built on databases, which were considered as a medium between virtual and real user environments for a specific medical application. Merging different components within a unified distributed application posits new essential problems for software. Particularly protection tools, which are sufficient separately, become deficient during the integration due to specific additional links and relationships not considered formerly. E.g., it is impossible to protect a shared object in the virtual operating room using only DBMS protection tools, if the object is stored as a record in DB tables. The solution of the problem should be found only within the more general application framework. Appropriate tools are absent or unavailable. The present paper suggests a detailed outline of a design and testing toolset for access differentiation systems (ADS) in distributed medical applications which use databases. The appropriate formal model as well as tools for its mapping to a DMBS are suggested. Remote users connected via global networks are considered too.