Allergic Inflammatory Processes Research Articles

Gonadal sex and chromosome complement influence the gut microbiome in a mouse model of allergic airway inflammation.

Evidence abounds that gut microbiome components are associated with sex disparities in the immune system. However, it remains unclear whether the observed sex disparity in asthma incidence is associated with sex-dependent differences in immune-modulating gut microbiota, and/or its influence on allergic airway inflammatory processes. Using a mouse model of house dust mite (HDM)-induced allergic inflammation and the four core genotypes (FCGs) model, we have previously reported sex differences in lung inflammatory phenotypes. Here, we investigated associations of gut microbiomes with these phenotypes by challenging FCG mice [mouse with female sex chromosome and male gonad (XXM), mouse with female sex chromosome and female gonad (XXF), mouse with male sex chromosome and male gonad (XYM), and mouse with male sex chromosome and female gonad (XYF); n = 7/group] with HDM (25 μg) or PBS intranasally for 5 wk and collecting fecal samples. We extracted fecal DNA and analyzed the 16S microbiome via Targeted Metagenomic Sequencing. We compared α and β diversity across genotypes and assessed the Firmicutes/Bacteroidetes (F/B) ratio. When comparing baseline and after exposure for the FCG, we found that the gut F/B ratio was only increased in the XXM genotype. We also found that α diversity was significantly increased in all FCG mice upon HDM challenge, with the highest increase in the XXF, and the lowest in the XXM genotypes. Similarly, β diversity of the microbial community was also affected by challenge in a gonad- and chromosome-dependent manner. In summary, our results indicated that HDM treatment, gonads, and sex chromosomes significantly influence the gut microbial community composition. We concluded that allergic lung inflammation may be affected by the gut microbiome in a sex-dependent manner involving both hormonal and genetic influences.NEW & NOTEWORTHY Recently, the gut microbiome and its role in chronic respiratory disease have been the subject of extensive research and the establishment of its involvement in immune functions. Using the FCG mouse model, our findings revealed the influence of gonads and sex chromosomes on the microbial community structure before and after exposure to HDM. Our data provide a potential new avenue to better understand mediators of sex disparities associated with allergic airway inflammation.

Unraveling The Impact: Mast Cells In Oral Pathology

Mast cells play a crucial role in the immune response, particularly in allergic reactions and inflammatory processes. In the context of oral diseases, mast cells have been implicated in various pathological conditions, including gingivitis, periodontitis, oral lichen planus, and oral cancer. This comprehensive review aims to explore the role of mast cells in the pathogenesis of these oral diseases, focusing on their activation, degranulation, and subsequent release of mediators such as histamine, cytokines, and growth factors. Furthermore, this review discusses the interaction between mast cells and other immune cells, as well as their involvement in angiogenesis, tissue remodelling, and pain modulation in the oral cavity. A thorough understanding of the role of mast cells in oral diseases may pave the way for the development of novel therapeutic strategies targeting mast cell activation and function, ultimately improving the management of these conditions.

LEVELS OF IL-4 AND Γ- INTERFERON IN CHILDREN’S BLOOD SERUM AS PREDICTORS OF ASTHMA FORMATION

Introduction. The prevalence of asthma continues to increase every year. Asthma is the leading chronic disease. Infl ammation,both acute and chronic, is closely related to the action of cytokines (pro- and anti-infl ammatory). T-helper 2 lymphocytesrelease IL-4, which triggers the production of immunoglobulin E (IgE) antibodies, which set the stage for allergy and activateinfl ammatory cells. The regulators of this process are T helper-1 lymphocytes, which produce cytokines (IFN-gamma) thatsuppress Th-2 activity. Disturbances in the ratio of Th-1/Th-2 lymphocyte clones are a subject of debate in the early detectionof asthma and the prediction of the development of this disease.The aim of the study was to evaluate the levels of IL-4 and γ-interferon in the blood serum of children with transient wheezeand asthma..Material and methods. 121 children were included in the study. The patients were divided into groups: group 1 – childrenwith transient wheezing (TW) (n = 81), group 2 – children with doctor- diagnosed asthma (DDA) (n = 15), group 3 – healthychildren (n = 25).IL-4 and γ-interferon in blood serum were analyzed by ELISA using commercial kits (human IL-4 and human γ-interferon“Vector Best- Ukraine”). Data were analyzed using Statsoft Statistica version 8 (Tulsa, OK) and the MedCalc version 17.2statistical program.The planned clinical trials were conducted after obtaining the approval of the local ethics committee (date: February 1, 2015;number: 2015/01) and were conducted in accordance with the principles of the Declaration of Helsinki, as amended in October 2013.This article was conducted within the framework of the Department of Pediatrics No. 2 of Kharkiv National MedicalUniversity «Medical and biological aspects of adaptation of children with somatic pathology to modern conditions. Predictionof asthma control in children taking into account infl ammatory markers and the state of the airway barrier of the lungs» (stateregistration number 0120U102471).Results. It was found that in children of the fi rst and second groups, in the midst of clinical manifestations of wheezing, IL-4levels signifi cantly increased and serum γ-interferon levels decreased. The highest levels of IL-4 and the lowest levels of serumγ-interferon were found in patients with DDA.Serum levels of IL-4 above 15.33 pg/mL and γ-interferon below 98.62 pg/mL in children with wheezing episodes may beconsidered as a possible indicator of asthma development.Conclusions. Serum IL-4 and γ-interferon are involved in the regulation of allergic infl ammatory processes in the body.A statistically signifi cant increase in IL-4 levels and a decrease in γ-interferon levels in the blood serum of patients with asthmais likely to indicate the development of a chronic form of infl ammation.

Medical therapy for conjunctivitis. Literature review

Conjunctivitis, according to various studies, is the most common reason for going to the initial outpatient appointment and can be caused by several factors at the same time. Treatment is carried out comprehensively, depending on the clinical picture, somatic status and anamnesis data. In accordance with the clinical guidelines developed by the Russian Association of Ophthalmologists, the following groups of drugs are recommended for use: antibacterial, antiseptic, antihistamine, nonsteroidal anti-inflammatory drugs.Purpose: to analyze the use of the above groups of drugs in the treatment of conjunctivitis in order to recommend a reasonable prescription of the necessary therapy.Materials and methods. The literature data on the study of the features of the action of the above pharmacological groups in the treatment of conjunctivitis, obtained on the resources of PubMed, eLibrary, Crossref Metadata, mainly over the past 20 years, are presented.Results. The presence of signs of an allergic reaction involves the appointment of antiallergic drugs with multiple pharmacological effects – blockade of histamine receptors, stabilization of mast cell membranes and suppression of eosinophil filtration. Given the different mechanisms of action within this group of drugs, it is necessary to select them individually. When prescribing tablet forms of antihistamines, it must be remembered that with prolonged use, they can cause patients to feel dry in their eyes. In cases where the above antiallergic drugs do not adequately control the allergic inflammatory process, anti-inflammatory drugs are used. Nonsteroidal and steroid anti-inflammatory drugs are used as anti-inflammatory drugs. Usually nonsteroidal anti-inflammatory drugs are recommended for use in chronic conjunctivitis and patients with a history of systemic diseases. Steroid drugs are indicated for severe forms of manifestation of the allergic process on the eyes, as well as the appointment of steroid anti-inflammatory drugs is recommended for use in short courses (up to 2 weeks), and with their longer use, control of intraocular pressure is necessary. Literature data indicate the lack of efficacy of antiviral drugs such as acyclovir and others from this group in the treatment of conjunctivitis of adenoviral etiology. Drugs with an immunomodulatory effect based on interferon or inducers of interferon synthesis are widely used. The prescription of antibiotics should be justified, since in recent years the level of resistance to them has significantly increased. Antiseptics that have a wide spectrum of action (bacteria, viruses, fungi and protozoa) are an alternative to antibiotics, but it must be remembered that this group of drugs often causes allergic reactions.Conclusion. The treatment of conjunctivitis must be approached carefully, taking into account not only the etiology of the disease, but also the somatic and immune status of the patient. To avoid the negative effects of the use of antibiotics, replace them with alternative drugs and do not use them in the treatment of conjunctivitis of a non-bacterial nature.

Allergy to Cow’s Milk Proteins and Other Allergens—An Unrecognized Co-Factor of Idiopathic Nephrotic Syndrome in Children or a Factor Interfering with the Treatment of This Disease? A Case Report

Idiopathic nephrotic syndrome (INS) is one of the chronic kidney diseases that occurs in childhood. Starting from a few case reports in the 1950s–1970s and up to the present, the relationship between idiopathic nephrotic syndrome (INS) and the occurrence of atopic disorders in these patients has been discussed in many medical publications. These publications show that in certain patients, mainly children and adolescents, but also in adults with INS, various clinical symptoms and laboratory indicators of an atopic allergic process may be present. This process has been shown to involve Th2 lymphocytes, to have an excessive production of interleukins (IL-4, IL-5, IL-13), and to have an increased serum level of immunoglobulin E (IgE). This leads to the development of a systemic allergic inflammatory process, of which the kidneys can also become the effector organ. The coexistence of an allergic process which may adversely affect the course of nephrotic syndrome may be confirmed by the increased serum IgE level and the hypersensitivity reaction of the patient’s body to various environmental allergens (through the presence of allergen-specific IgE /asIgE/ antibodies to food, pollen, mould, dust, or other allergens in the blood serum). High concentrations of IL-13 and other plasma mediators of this inflammation (e.g., histamine, bradykinin) structurally and functionally damage the renal filtration barrier, and in particular, the function of podocytes in the glomeruli. Podocyte dysfunction disturbs the physiological process of plasma filtration in the glomeruli, leading to excessive protein loss in the urine. These disorders initiate the development of idiopathic nephrotic syndrome in these patients. This publication presents the coexistence of an allergic process caused by allergy to cow’s milk proteins and hypersensitivity to other allergens in a child with idiopathic nephrotic syndrome. This publication also assesses whether treatment of the allergic process coexisting with INS with an elimination diet (milk-free, hypoallergenic) and anti-allergic drugs affected the course and treatment of INS in this child.

The effectiveness of the use of feed additives "AGROFIT PRO" in the diets of piglets

The article presents the results of studies on the effect of a multi-enzyme feed additive "AGROFIT PRO" on the safety, live weight gain, feed conversion and morpho-biochemical blood parameters of piglets of the rearing group. The investigated additive contains at its core the enzyme phytase and a complex of NPS enzymes, a strain-producer of Penicillium verruculosum, as well as fillers: corn starch; sodium chloride. It is used to improve the digestibility of feed, increase the safety of growth and productivity of farm animals. To set up the experiment, four groups (three experimental and one control) of piglets, 56 heads each, were formed, which were kept in a specialized farm room for the rearing group. During the experiment, all piglets were in identical conditions of keeping and feeding. The research results showed that the safety of piglets in the first and second experimental groups was at the level of 100%, and in the control and third experimental groups it was 96.4%. The increase in the experimental group was 3.8%, 1.2% and 0.3% compared to the control group, and in the experimental groups there was a decrease in feed conversion by 2.1% and 3.4%. Based on the obtained data of the general analysis of the whole blood of piglets, it can be concluded that there are no allergic reactions, pathological and inflammatory processes in the body when giving the experimental animals the studied feed additive. When conducting biochemical studies of blood serum, all the studied parameters were within the intraspecies norms; according to the results of the study, there was no negative effect of the feed additive on the organ systems of the experimental animals under test. A statistically significant difference was recorded between the control and the third experimental group in terms of creatinine, which was higher by 12.9%, and triglycerides by 34.9%.

Microscopic, submicroscopic characterization of pro- and anti-inflammatory cell phenotypes of the lungs in conditions of experimental allergic inflammation

The aim is to study the microscopic and submicroscopic characteristics of pro- and anti-inflammatory cell phenotypes of the lungs under conditions of experimental allergic inflammation. Material and methods. We used histological and electron microscopic methods to study the lungs of 48 male guinea pigs in experimental ovalbumin-induced allergic inflammation, simulated by subcutaneous sensitization and subsequent intranasal inhalation with ovalbumin. Submicroscopic changes of respiratory endocrine cells, goblet cells, exocrine bronchiolar cells, mast cells, macrophages, eosinophils, endothelial cells of guinea pigs lungs were determined. Results. The most significant reactive submicroscopic changes were established on the 23rd and 30th days of observation in the form of an increase in the functional activity of exocrine bronchiolar and goblet cells, as evidenced by the presence of a light nucleus with a predominance of euchromatin, nucleoplasm of low electron-optical density, nucleoli, developed granular endoplasmic reticulum and an increase in the number of goblet cells secretory mucous granules by electron microscopic examination. The revealed ultramicroscopic features of respiratory endocrine cells (an increase in a number of “empty” core dense vesicles), eosinophilic granulocytes (piecemeal degranulation), an increase in the number of mast cells granules, numerous pseudopodia in macrophages are the confirmation of the active participation of these cell phenotypes in the initiation of inflammation during the early period of the allergic inflammatory process in lungs. Conclusions. A significant reaction of the innate nonspecific and adaptive immunity occurs in airways during the experimental ovalbumin-induced allergic inflammation, consisting primarily of the functional activation of eosinophilic granulocytes, mast cells, and macrophages, as well as an increase in the secretory activity of exocrine bronchiolar cells and goblet cells, which is confirmed by the changes investigated by electron microscopic examination and are accompanied by reactive changes in the vessels of microcirculatory bed.

Dynamics of the cellular composition of lymphoid nodules in the lungs of guinea pigs sensitized with ovalbumin

The article discusses the morphological aspects of the dynamics of the cellular composition of lymphoid nodules in the lungs of guinea pigs as a result of an experimental ovalbumin-induced allergic process. We studied the reactivity of immunocompetent cells of lymphoid formations of the lungs after three times subcutaneous sensitization and subsequent 8-day intranasal aeroallergization with ovalbumin in the early and late stage period of the allergic inflammatory process by microscopic, morphometric and statistical methods. By help of morphometric analysis we demonstrate the general regularity of reactivity of a local specific link of the pulmonary immune system to the action of an allergen, which consists in the elevation of the average amount of immune cells of lymphoid nodules of the lungs, starting from the 30th to the 44th day after the start of the experiment. The maximal coefficient of increase by 5.8 times was observed in counting plasma cells among all types of immunocompetent cells of lymphoid nodules in the lungs during the experiment. It has been statistically proven that the implementation of the ovalbumin-induced allergic inflammatory process in the lungs proceeds according to the humoral type and the duration of its course is not limited by the direct influence of the allergen, it also continues after the end of its action, which is a manifestation of changes in compensatory-adaptive processes in the pulmonary immune system with ovalbumin-induced allergic inflammation.

Neuronal-Immune Cell Units in Allergic Inflammation in the Nose.

Immune cells and immune-derived molecules, endocrine glands and hormones, the nervous system and neuro molecules form the combined tridirectional neuroimmune network, which plays a significant role in the communication pathways and regulation at the level of the whole organism and local levels, in both healthy persons and patients with allergic rhinitis based on an allergic inflammatory process. This review focuses on a new research paradigm devoted to neuronal-immune cell units, which are involved in allergic inflammation in the nose and neuroimmune control of the nasal mucociliary immunologically active epithelial barrier. The categorization, cellular sources of neurotransmitters and neuropeptides, and their prevalent profiles in constituting allergen tolerance maintenance or its breakdown are discussed. Novel data on the functional structure of the nasal epithelium based on a transcriptomic technology, single-cell RNA-sequencing results, are considered in terms of neuroimmune regulation. Notably, the research of pathogenesis and therapy for atopic allergic diseases, including recently identified local forms, from the viewpoint of the tridirectional interaction of the neuroimmune network and discrete neuronal-immune cell units is at the cutting-edge.

Показники цитокінового статусу дітей раннього віку з алергічним ураженням шлунково-кишкового тракту залежно від забезпеченості вітаміном D

The rapid growth in the prevalence of allergic diseases among children in the modern world dictates the need for detailed study of pathogenetic mechanisms, the search for new methods of diagnosis, treatment and prevention of this pathology. Recent studies of the important immunological effects of vitamin D in allergic pathology make it important to study its effect on the course of gastrointestinal food allergy (GIFA) in young children. Purpose - to determine the serum concentrations of IL-10 and IL-17 in young children with GIFA, depending on the supply of vitamin D. Materials and methods. We examined 34 children aged from 2 months to 3 years with isolated gastrointestinal symptoms or a combination of gastrointestinal and skin symptoms associated with food. The comparison group consisted of 22 children of the same age with an unencumbered individual and family history of allergies. All examined children had quantified serum cytokine (IL-10, IL-17A) levels by enzyme-linked immunosorbent assays and serum hydroxycalciferol (25(OH)D) levels. Vitamin D deficiency in subjects was considered at a concentration of 25(OH)D in serum <20 ng/ml (or <50 nmol/l), a concentration of 21 ng/ml to 29 ng/ml (or from 50.1 nmol/l up to 74.9 nmol/l) was assessed as vitamin D deficiency. A sufficient concentration of vitamin D was considered to be 25(OH)D serum level >30 ng/ml. Data of clinical and laboratory researches were processed by methods of mathematical statistics accepted in biology and medicine. Results. There was a significantly increase in the average concentrations of IL-17A (180.4±23.0 pg/ml) and IL-10 (113.8±15.0 pg/ml) in children with gastrointestinal food allergy and in the comparison group - 45.7±18.1 pg/ml and 32.1±11.4 pg/ml, respectively, (p<0.05), which reflects the intensity of the allergic inflammatory process in the gastrointestinal tract. In children with allergic gastrointestinal inflammation who were deficient in vitamin D, the mean concentrations of proinflammatory cytokine IL-17A and regulatory cytokine IL-10 were significantly higher than in children with GIFA and optimal supply of vitamin D 244.9±19.7 ng/ml and 49.45±2.14 ng/ml respectively against 135.2±33.3 ng/ml and 26.41±1.81 ng/ml respectively, (p<0,05), which indicates a more intense activity of the inflammatory process in the intestine of children with insufficient supply of vitamin D. Conclusions. Allergic gastrointestinal inflammation in young children is characterized by increased concentrations of serum proinflammatory and regulatory cytokines - IL-10 and IL-17A, that is a protective reaction of the immune system and can be used as a marker of allergic inflammation in GIFA. The study of the regulatory effect of vitamin D on the expression of cytokines (IL-10 and IL-17A) in allergic gastrointestinal inflammation in young children will optimize the pathogenetic treatment of gastrointestinal food allergies. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local ethics committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors. Key words: cytokine status, young children, allergic pathology of the gastrointestinal tract, vitamin D.

The resistive region of pulmonary microvessels in ovalbumin-sensitised guinea pigs: a quantitative and qualitative histological study

This work aimed to study the morphofunctional changes in the resistive region of the pulmonary microcirculatory bed in ovalbumin- sensitised guinea pigs. Using histological, morphometric, and statistical methods, we studied the lungs of 48 male guinea pigs in conditions of the experimental allergic inflammatory process. To assess the structural and functional state of medium (51– 125 μm) and small (25–50 μm) arterioles, the outer and inner diameters, the thickness of the tunica media, and the Kernogan index were determined. The most pronounced changes, such as thickening of their walls and narrowing of the lumen in the late stages of the allergic inflammatory process, consisted in the restructuring of medium arterioles. Compared to control animals, the inner diameter of the medium arterioles decreased three times (p*/**<0.05) in experimental group 4; the thickness of the tunica media of medium arterioles increased two times (p*/**<0.05) in experimental group 3. These changes are the result of the increasing tone and hypertrophy of the smooth muscles of the tunica media and the decreasing capacity of arterioles as evidenced by a statistically significant increase of the Kernogan index-indicated hypertrophy and the increasing tone of the smooth muscles of the tunica media and decreasing vascular throughput.

Bilastine - Novel anti histamine drug for allergic rhinitis

The immune system is a fundamental part of human protection against infection and disease.The immune system can occasionally lead to unfavourable reactions in the host which are known as hypersensitivity reactions. The exaggerated immune reactivity (hypersensitivity) to certain environmental substances (allergens) like airborne pollens, dust, mites, pet dander, and reactions to certain foods that normally have little effect on most people is known as allergy. The incidence of allergic disease like allergic rhinitis (AR), food borne allergy, asthma and anaphylactic reactions are prevalent in 25% of populations predominately in adolescents and adults in industrialised countries. Bilastine is a novel second-generation non-sedative, highly selective histamine H1 receptor antagonist that suppresses some allergic inflammatory processes that inhibits the release of histamine from mast cells and is approved in the treatment allergic rhinitis, urticaria and pruritus associated with skin diseases. This review covers the safety, efficacy and pharmacological aspects of Bilastine as an important product for treatment of allergic rhinitis.

The possibility of using anti-human monoclonal antibody CD3 as pan T-cell marker in guinea pigs

The present study was aimed to evaluate the possibility of using anti-human monoclonal antibody CD3 as pan T-cell marker in the guinea pigs’ trachea and lung in early and late manifestations of the allergic inflammatory process.
 Materials and methods.We have studied the distribution and quantitative changes of CD3-positive lymphocytes in trachea and lung of guinea pigs using histological, immunohistochemical, statistical methods in conditions of experimental inflammatory process.
 Results. Our results revealed the applicability of anti-Human monoclonal antibody CD3 (Clone SP7, «DAKO», Denmark) cross-reaction with T-cells of guinea pigs’ tracheas and lungs. The most statistically significant elevation of the number of CD3-positive lymphocytes, in comparison with the control group (p*/**<0.05), observed in the experimental group III in the late stages of experimental inflammatory process. The elevation of the number of CD3-positive lymphocytes persists even after the termination of the allergen action, which indicates the continuation of the reaction of pulmonary local adaptive immunity to the allergen.
 Conclusions. The results of our study may be useful in conditions of the deficiency of guinea pig-specific tests. The immunohistochemical assessment of guinea pigs’ trachea and lungs proved the possibility to use anti-Human monoclonal antibody CD3 as a panT-cell marker in guinea pigs. We demonstrated the activation of adaptive immune response (T-cells), represented by their immunohistochemical changes, predominantly in the late stages of experimental inflammatory process.

Morphological features of the respiratory part in guinea pigs lung in dynamics of experimental allergic inflammatory process

The main function of the components of the respiratory tract is gas exchange while maintaining homeostasis in lung, given the pathogenic and non-pathogenic elements of the environment contained in the inhaled air. Morphological changes of the components of the respiratory part in lung of human and animals of adaptive nature under the influence of various factors on the body today remain insufficiently studied. The aim of the study was to investigate the morphological changes of the components of the respiratory part of guinea pigs lung in the dynamics of experimental ovalbumin-induced allergic inflammation. We used histological and electron microscopic methods to study the lungs of 48 male guinea pigs in experimental ovalbumin-induced allergic inflammation, simulated by subcutaneous sensitization and subsequent intranasal inhalation with ovalbumin. Morphological changes of the components of the respiratory tract of the lungs were determined in the early and late phases of allergic inflammatory process at the optical and submicroscopic levels. The early phase (23rd and 30th days of the experiment) was characterized by a predominance of alterative and destructive changes, consisted in the desquamation of the alveolar epithelium with a violation of the blood-gas barrier and hemomicrocirculatory bed. Type II alveolar cells had lesions of varying severity in the form of the absence of lamellar bodies or disturbances in the formation of their contents, vacuolization of the cytoplasm, mitochondrial damage. In the late phase of the development of the allergic inflammatory process (36th and 44th days of the experiment) in the respiratory part of lung were dominated adaptive and restorative changes. In addition, we observed dilation of the lung alveoli and thinning of the interalveolar septa, which is a consequence of the cascade of reactions of the local neuroendocrine and immune systems of lung as a result of allergen action. Thus, experimental ovalbumin-induced allergic inflammatory process of the respiratory tract is accompanied by structural and functional changes in the components of the respiratory part in lung of guinea pigs in stages depending on the duration of the experiment.

Examination of Sex Differences in a Chronic Rhinosinusitis Surgical Cohort.

Sex discrepancies have been reported in chronic rhinosinusitis (CRS), but limited data exist exploring sex-specific biological processes and sinonasal quality of life. Prospective cohort. Academic medical center. Demographics, clinical data, and sinonasal mucus were collected from patients with CRS presenting for surgical consideration over a 5-year period. A random forest model and linear regression were used to assess predictor variables for the 22-item Sino-Nasal Outcome Test (SNOT-22) and subdomains. Enzyme-linked immunosorbent assays were used to measure substance P and tryptase in a subset of mucus samples to explore biological differences by sex. In total, 520 patients were studied (mean age 48.3 years, 50.9% female). Males were older (50.1 vs 46.6 years, P = .008), had more polyp disease (48.2% vs 35.5%, P = .004), and had higher mean Lund-Mackay CT score (11.3 vs 9.5, P = .004). Females had a higher overall mean SNOT-22 (40.9 vs 46.9, P = .001) and higher scores in ear/facial, psychological, and sleep domains (P < .01). Age, objective disease measures, and sex were top predictors for total SNOT-22. Neither mucus substance P or tryptase, alone or paired with sex, correlated with total SNOT-22. Analysis of mucus biomarkers by sex revealed correlation between mucus tryptase in females with the extranasal subdomain (P = .01). Sex differences exist in CRS disease manifestations and presentation for surgical consideration. Detection of mucus (substance P and tryptase) was reliable, but in this exploratory study, we were not able to establish neurogenic or allergic inflammatory processes as a large source of differential disease features between sexes.

4-Carvomenthenol, a monoterpene of essential oils, and its underlying effects on anti-inflammatory activity and immediate hypersensitivity reaction

The monoterpene 4-carvomenthenol (Carvo) is found in essential oils of plant. Here, we evaluate the Carvo oral pretreatment in acute inflammatory experimental models and in silico molecular docking. Mice pretreated with Carvo were challenged and submitted to the protocols: paw edema, peritonitis, scratching behavior and anaphylactic shock reaction. Besides, we used histamine H1 receptor, cyclooxygenases (COX-1 and COX-2) and phospholipase A2, as targets for molecular docking analysis. Carvo inhibited the carrageenan-induced paw edema and decreased the peritoneal influx of polymorphonuclear cells on carrageenan-challenged mice without interfering with the mononuclear cell influx. Moreover, Carvo diminished the histamine, PGE2 and compound 48/80 induced paw edematogenic effect. The monoterpene also diminished the mice scratching behavior and, surprisingly, avoided the animal death caused by compound 48/80 in 30 min. Through the docking analysis, Carvo showed favorable binding energy to the histamine H1 receptor. This study demonstrates that Carvo attenuated the allergic inflammatory process, decreasing edema, cell migration, activation of mast cells and the histamine release, probably due to interaction of Carvo with the histamine H1 receptor, ameliorating the itching and the anaphylactic shock reaction. Therefore, the results of this study indicate that Carvo has anti-inflammatory properties by reducing the histamine effects.

Morphfological changes in the membranes of the trachea of guinea pigs in experimental ovalbumin-induced allergic inflammation of the airways.

Background. In recent years, there has been an increase in the number of allergic diseases of the respiratory organs, especially in children. The predictor of the further development of bronchial asthma is sensitizing at an early age to the allergens of chicken egg. The use of new knowledge about the allergenic components of the chicken egg will predict the risks and clinical features of the disease. Despite the importance, the problem of morphogenesis of allergic inflammation of the wall of the trachea is not sufficiently studied, so far many issues are not found in morphology and require further research. Objective.The aim of the study is to establish morphological changes in the tracheal membranes in experimental ovalbumin-induced allergic inflammation of the airways of guinea pigs. Methods. The thickness of tracheal wall of 48 male guinea pigs was investigated by histological, morphometric, statistical methods on the twenty-third, thirty-sixth, thirty-sixth and forty-fourth days after the initiation of the experimental ovalbumin-induced allergic inflammation of the airways. Results. We have found, that maximum statistically significant thickening is shown in the late period of tracheal mucosa in 2 times on the 44th day of observation and tracheal submucosa in the 3rd experimental group on the 36th day of observation (increasing coefficient 2) compared to the control. However, the thinning of tracheal submucosa is observed in the early period of the inflammatory process on the 23rd and 30th day of observation. It has been proved, that the allergic inflammation of the tissues of the trachea caused by the sensitization and allergization of ovalbumin leads to the change in the thickness of layers of trachea in the chronobiological aspect. Conclusion. On the 23rd and 30th days of the experiment, thinning of tracheal mucosais observed due to damage of epithelial cells. Thickening of tracheal mucosa and submucosa was found in the third and fourth groups of observation (late period of allergic inflammation) compared with animals of the intact group and the control group due to an increase in the area of loose connective tissue, which is a consequence of the continuation of the allergic inflammatory process in the trachea after the end of the experiment.

MORPHOLOGICAL CHARACTERISTICS OF GUINEA PIGS BRONCHUS ASSOCIATED LYMPHOID TISSUE IN THE DYNAMICS OF EXPERIMENTAL OVALBUMIN-INDUCED ALLERGIC INFLAMMATION

The actual problem of modern medicine is the reaction of Bronchus associated lymphoid tissue in airways chronic allergic diseases, because the full functioning of the respiratory system depends on the state of its local immune system.&#x0D; The aim – to study morphological changes in Bronchus associated lymphoid tissue of guinea pigs in the dynamics of experimental ovalbumin-induced allergic inflammation.&#x0D; Material and Methods. We have studied the lung of 48 guinea pigs, using histological and morphometric methods, under conditions of experimental ovalbumin-induced allergic inflammation. To assess the structural and functional rearrangement of pulmonary lymphoid nodules, their diameter and number were determined.&#x0D; Results. We have shown that sensitization and allergization with ovalbumin leads to a significant structural and functional rearrangement of Bronchus associated lymphoid tissue of guinea pigs in the form of the elevation in their number and diameter. We found more pronounced morphological changes in the late period of development of allergic inflammation in peribronchial lymphoid nodules, confirmed by the maximum magnification factor – 2.6 (p*/**&lt;0.001) of the diameter of peribronchial lymphoid nodules in the 4th experimental group compared to the control.&#x0D; Conclusions. Sensitization and inhalation with ovalbumin leads to structural reorganization of Bronchus associated lymphoid tissue of guinea pigs in the form of the elevation in their number and diameter, had the unidirectional staged character depending on localization of lymphoid nodules and the duration of the experiment and claimed proliferative changes in the cellular adaptive link of local lung immunity of guinea pigs in late period of allergic inflammatory process.

Reaction of eosinophilic granulocytes of guinea pigs airways to the experimental allergic inflammation according to the morphometric study

Background. After creating an animal model of experimental airways allergic inflammation using ovalbumin, scientists mainly studied the reaction of the cellular and humoral links of the acquired specific immunity. At the same time, it is known that the development of allergic inflammation of the airways to the effect of the environmental chemoattractants is primarily the result of the local innate immune system response. Pulmonary neuroendocrine cells of the airway epithelium with the help of neuropeptides activate the secretion of IL-5 and IL-13 by type 2 innate lymphoid cells IL-5 determines the eosinophilic inflammation. The question of the reaction of the components of innate immunity of the respiratory tract to the allergic inflammation in most aspects remains open. open. Objective. The purpose of the current study was to define the reaction of eosinophilic granulocytes in guinea pigs lungs as an important component of the innate immunity of the respiratory tract to experimental ovalbumin-induced allergic inflammation according to the data of a morphometric study. Methods. Histological, morphometric, statistical methods were used to study the topographic features and the number of eosinophils in the lungs of male 48 guinea pigs on the 23rd, 30th, 36th and 44th days after initiation of the experimental ovalbumin-induced allergic airway inflammation. Results. Our study demonstrates a significant reaction occurs on the part of the cellular link of innate immunity, which consists in the activation of eosinophils, in the experimental model of ovalbumin-induced airways allergic inflammation. The most significant changes were observed in the distal parts of the intrapulmonary airways and in the structures of the pulmonary acinus in the early period of the development of the inflammatory process (23rd and 30th days after the start of the experiment). The late (36th and 44th days after the start of the experiment) period of the development of an allergic inflammatory process in the lungs is accompanied by a gradual decrease in the activity of eosinophilic inflammation. At the same time, the quantitative indicators remain statistically significantly higher in the intact and control groups, which indicates the continuation of allergic inflammation in the absence of the action of the allergen and is a manifestation of the violation of the recovery and adaptation processes in the local immune system of the lung. Conclusion. After ovalbumin-sensitization and aeroallergization eosinophilic inflammation develops in the lungs of a guinea pig, as a result of the reaction of the innate immunity to the action of an allergen. Actively and first of all, allergic eosinophilic inflammation develops in the distal airways (terminal bronchioles) and in the connective tissue stroma of the pulmonary acinus.

A Randomized Controlled Pilot Trial to Test the Efficacy of Intranasal Chlorpheniramine Maleate With Xylitol for the Treatment of Allergic Rhinitis.

The prevalence of allergic rhinitis (AR), including symptoms of sneezing, nasal itching, airflow obstruction, and nasal discharge caused by histamine and immunoglobulin E (IgE)-mediated reactions, is ~30% in the U.S. Recent studies seem to suggest that the allergic inflammatory processes in AR may be induced by the interaction between an allergen (trigger) and the nasal microbiome (substrate). In this study, we have identified two agents with antihistaminic and microbiome-modulating characteristics that can be administered intranasally, namely, chlorpheniramine maleate (CPM) and xylitol (X). This study aimed to test the efficacy of intranasal CPM plus xylitol (CPM+X) nasal for the treatment of AR in an outpatient setting. A multicenter, randomized, double-blind, 30-day pilot study was conducted during the spring of 2019. After starting five days of placebo therapy (run-in period), patients with moderate-to-severe AR nasal symptoms were randomized to treatment with CPM+X (n=16) spray and nasal saline placebo (PLB; n=13). Both treatments were administered in the form of one spray dose (~100 µL of the solution containing 1.25 mg CPM) per nostril twice a day. Outcome variables were the changes in visual analog scale (VAS) and daily symptoms score (DSS) at days 1, 5, 10, 15, 25, and 30 after the initiation of the treatment. ANOVA (analysis of variance) with repeated revealed a significant treatment-by-time interaction such that the CPM+X group had a significant decrease (p < 0.05) in both DSS (∆-3.0 ± 2.7) and VAS (∆-3.8 ± 2.0) scores compared to PLB after 30 days. The difference in DSS and VAS scores between the groups was evident just after five days (day 10) of using CPM+X. The CPM+X scores were significantly lower (p < 0.008) starting from day 10 compared with day 1, whereas there were no statistically significant (p > 0.008) changes in the PLB during the 30-day treatment window. The present data suggest that nasal CPM+X use effectively improves AR symptoms. A large-scale study of the long-term effects of CPM+X for the treatment of other chronic respiratory disorders and the potential microbiome-modulating effects warrants further investigation.