IL-6 Gene Expression as a Marker of Pathological State in Psoriasis and Psoriatic Arthritis.

The expression of the IL-6 gene in mononuclear blood cells of 45 patients with psoriatic arthritis and 31 patients with plaque psoriasis was studied for possible differential diagnosis of the pathologies. The expression level of IL-6 in psoriatic arthritis and psoriasis surpassed that in healthy controls by 192 and 147 times, respectively. Significant differences in the gene expression were revealed between the patients with psoriatic arthritis and mild psoriasis. The level of IL-6 in patients with severe psoriasis approached that in patients with psoriatic arthritis. High level of IL-6 gene expression can be a marker of possible joint damage in patients with psoriasis and a signal for revising the therapeutic approach in a particular patient.

Efficacy and Safety of Ergoferon in Children from 6 Months to 6 Years Old with Acute Respiratory Viral Infections in Contemporary Outpatient Practice: A Multicenter, Double-Blind, Placebo-Controlled Randomized Trial.

To evaluate the efficacy and safety of Ergoferon in combination with symptomatic therapy in children from 6 months to 6 years old with acute respiratory infections (ARI) in contemporary outpatient practice, an international, multicenter, double-blind, placebo-controlled, randomized, parallel-group clinical trial was performed. Derived by technological treatment of antibodies to interferon gamma, histamine, and CD4, Ergoferon was previously proved to modulate its molecular targets promoting effective antiviral protection. The data of 282 patients with oral temperature ≥38.0°C plus mild to moderate severity of flu-like nonspecific and nasal/throat/chest symptoms were included in intention-to-treat analysis (n = 140, Ergoferon group; n = 142, placebo group). Time to alleviation of all ARI symptoms was the primary endpoint, and 8 outcome measures were estimated as the secondary endpoints. Respiratory viruses were confirmed in 57.1% (Ergoferon) and 54.9% (Placebo) of patients. Compared to placebo, Ergoferon reduced time to alleviation of all ARI symptoms (4.5 ± 1.7 versus 5.2 ± 2.2 days in placebo; p=0.026) including fever (2.8 ± 1.5 vs 3.4 ± 2.0; p=0.031), flu-like nonspecific (4.0 ± 1.8 vs 4.7 ± 2.2, p=0.022), and nasal/throat/chest (4.3 ± 2.0 versus 5.0 ± 2.3; p=0.024) symptoms. Ergoferon add-on therapy decreased the mean total symptom severity score (according to 4-point scale for each symptom), ARI severity, frequency of antipyretic use, and percentage of complication requiring antibiotics and increased the percentage of recovered patients. The incidence of adverse events (AEs) in the Ergoferon group was significantly lower compared to the placebo group (7.0% versus 18.8%; p=0.004) including infectious diseases (3.5% vs 12.5%; p=0.008). In the Ergoferon group, AEs were mild or moderate. In 8 (57.1%) cases, AEs were unrelated to Ergoferon, in 5 (35.7%), the relationship was uncertain, and in 1 (7.1%), it was possible (mild rash on the face). Ergoferon treatment is beneficial for infants and young children with ARI in contemporary outpatient practice. Being well-tolerated, Ergoferon increases the symptomatic therapy effectiveness and improves the patient condition and disease outcomes.

[Prospects for the correction of intestinal microbiota in the prevention and treatment of asthma in children].

The issues of therapy and prevention of asthma in children do not lose their relevance. The increase in the prevalence of allergic diseases and asthma is associated, among other things, with a relative deficit in the microbial load and changes in the microbiota due to improved hygiene and living conditions. The microbiota plays an important role in the formation and functioning of the immune system. Contact with microorganisms contributes to the normal maturation of T-regulatory cells, preventing an inadequate immune response in both the Th1- and Th2-pathways. Aim - literature review on the possibilities of gut microbiota correction for prevention and treatment of asthma in children. Results. In children with an increased risk of asthma, abnormalities in the intestinal microbiota are observed in the first year of life: there is a relative deficiency of Lachnospira, Veillonella, Faecalibacterium and Rothia. The imbalance of the intestinal microbiota is accompanied by a decrease in the synthesis of short-chain fatty acids (butyrate, acetate, propionate), which, among other things, play the role of signaling molecules. Gut microbiota maturation is delayed in children at risk of asthma. It is not clear whether the diversity of the gut microbiota is associated with the risk of developing asthma. Maintenance of normal gut microbiota or correction of its disturbances in early life is a possible approach to the prevention and treatment of asthma. Breastfeeding, vaginal delivery, constant contact with farm animals or dogs since an early age, limiting antibiotic use in the first year of life, a varied diet with the inclusion of fiber-rich foods, and the use of pre- and probiotics can help. However, the implementation of these recommendations in practice is difficult. Further research is required to identify specific prophylactic stimuli reproducible in the urban environment. The conflicting results of studies in this area, in particular, the effectiveness of probiotics in the prevention of asthma, require large-scale prospective cohort studies with a long follow-up period and careful selection of probiotic strains and their combinations. Now, there are no definitive recommendations on the use of probiotics for the prevention of allergic diseases. Conclusion. The possibilities of correcting the gut microbiota for the prevention and treatment of asthma are actively studied, but at present, there are many contradictions and unresolved issues.

[Topical drugs for the treatment of non-streptococcal acute tonsillopharyngitis in children: results of a multicenter study]. / Topicheskie preparaty dlya lecheniya nestreptokokkovogo ostrogo tonzillofaringita u detei: rezul'taty mnogotsentrovogo issledovaniya.

INTRODUCTION: Acute tonsillopharyngitis (ATP) is a very common disease in children. In non-streptococcal ATP, systemic antibiotics are usually not indicated, but topical antimicrobial therapy is advisable. OBJECTIVE: To evaluate the effectiveness of the combination of cetylpyridinium chloride with gramicidin C in the form of a spray in children with ATP in a prospective multicenter non-interventional study.Patients and methods. The study included 94 patients aged 6-15 years with non-streptococcal ATP. A standard examination, assessment of the pain intensity in the throat using a visual analogue scale, assessment of the pain frequency during swallowing and a score assessment of objective manifestations were carried out. Sixty-eight patients of the main group received a combination of cetylpyridinium chloride with gramicidin C (Grammidin for children) in the form of a spray, 26 patients of the control group received throat irrigation with saline solution (based on sea water) for 7 days. Therapy was assessed after 1 day (by phone), 4 and 8 days (by examination). RESULTS: The groups of patients did not differ significantly in terms of demographic indicators and initial clinical manifestations. Body temperature initially did not differ, but was significantly lower in the main group after 1 (p=0.003) and 4 (p=0.04) days. The sore throat pain intensity decrease in the main group significantly exceeded this indicator in the control group after 1 (p<0.001) and 4 (p <0.001) days. Initially, swallowing pain was observed in all patients, after 4 days the complaint was significantly less frequent in the main group (p<0.001). The total assessment of objective data was significantly lower in the main group after 4 (p<0.001) and 8 (p<0.001) days. No adverse effects of pharmacotherapy were observed. CONCLUSIONS: The study showed high efficacy and safety of the cetylpyridinium chloride and gramicidin C (in the form of a spray) combination for non-streptococcal ATP in children aged 6-15 years.

[The problem of insomnia in infant/young children: issues of diagnosis and treatment]. / Problemy narusheniya sna u detei rannego vozrasta: voprosy diagnostiki i korrektsii.

OBJECTIVE: To obtain further evidence of the efficacy of dormikind in infant/young children. MATERIAL AND METHODS: The study was performed in the group of 114 patients, aged 6 months to 2.5 years, with sleep and sleep initiation disorders. Sixty-four patients received treatment with dormikind (group 1) and 50 patients received behavioral therapy (group 2) for 28 days. RESULTS AND CONCLUSION: In group 1, sleep initiation decreased by 1.7 times and reached 26.2±4.8 minutes, the number of children sleeping on hands dropped by 8.7 times and sleeping in the parent's bed by 2 times. In group 2, the same characteristics changed by 1.1, 1.3 and 1.5 times, respectively, and sleep initiation reached 33.4±2.9 minutes. The number of patients of group 1 falling asleep in their own beds increased by 3.2 times vs 1.2 times in group 2. Duration of night sleep increased and frequency of awakening reduced as well. The significant positive dynamics was noted in the emotional-behavior state of children after therapy: the total score significantly improved by 2.9 times to the end of treatment compared to group 2 (by 1.3 times). IMOS score showed significant difference between the groups on «total recovery¼ and «significant improvement¼. Therefore, the high efficacy and safety of dormikind in children have been confirmed.

Effect of Nasal Obstructive Disorders on Sinonasal Symptoms in Children with Different Levels of Bronchial Asthma Control.

Allergic rhinitis (AR) and allergic rhinosinusitis (ARS) are typical upper airway pathologies (UAP) in children with bronchial asthma (BA) frequently accompanied with nasal obstructive diseases (NOD). In order to establish the effect of NOD on correlations between nasal and synonasal symptoms with clinical assessments of asthma control, 82 children, 9.8 [8.9; 10.7] years old, with atopic BA were assessed using ACQ-5 for the BA control level, TNSS for nasal symptoms, and SNOT-20 for synonasal quality of life in combination with rhinovideoendoscopy for NOD. All patients had AR/ARS; in 76.3% (63/82) of children, UAP had a multimorbid character with the presence of NOD. Significant correlations were found between ACQ-5 and TNSS (R=0.40, p < 0.0001) and ACQ-5 and SNOT-20 (R=0.42, p < 0.0001). Correlations between TNSS/ACQ-5 and SNOT-20/ACQ-5 were higher in patients who do not have a combination of AR/ARS with NOD (R=0.67, p=0.0012; R=0.50, p=0.022, resp.) than in patients who have AR/ARS combined with NOD (R=0.30, p=0.015; R=0.26, p=0.04, resp.). Thus, the association of BA control level with the expression of nasal and synonasal symptoms is higher in children who do not have multimorbid UAP.

[Can cross-allergic reactions to food antigens be the cause of recurrent pancreatitis in children with food allergies?].

Drug and food allergy in 80% of cases are the cause of duodenal inflammation disrupting the function of the pancreatic ducts. However, in some cases, elimination diet in patients with food allergy does not provide a sufficient effect. The article shows the effect of cross-allergic reactions on recurrent pancreatitis in 28 children with food allergy (mean age 11.7 +/- 2.9 years). As an additional diagnostic criterion the coefficient of degranulation of mast cell in the intestinal mucosa (the ratio of degranulated forms to granulated) was determined, through which the effect of cross-allergic reactions (between food antigens and drugs of animal origin) on the duration and frequency of exacerbations of chronic pancreatitis in children with food sensitization has been shown. The exception of enzyme preparations for children with sensitization to pork and exception of eubiotics prepared using sucrose-gelatin-milk medium for children with sensitization to cow's milk and beef led to feel better in a shorter time (2-3 days) and to reduce the frequency of relapses. Catamnesis observation for 3 years showed that the incidence of recurrent exacerbations of the disease in 11 children with excepted cross-allergic reactions in the first year of follow-up was 9.1%, in the second year--9.1% and in the third year--0%, while in control group (17 children) the frequency of exacerbations was respectively 23.5; 35.3; 35.3%. In patients of the main group there was a slight overall increase of mast cells in the intestinal mucosa from 211.7 to 230.2 mm2 (p > 0.05) with decreasing of degranulated forms from 163.6 to 138.71 mm2 (p > 0.05) and significant increase of granulated forms from 47.41 to 91.51 mm2 (p < 0.05), resulting in a significant decrease in mast cells degranulation coefficient from 3.2 +/- 0.62/mm2 to 1.24 +/- 0.26/mm2 (p < 0.0001). Thus, duodenal etiology of recurrent pancreatitis caused by exposure to food antigens or cross-allergic reactions can be diagnosed with an additional diagnostic criterion--the coefficient of mast cell degranulation, whose exponents greater than 1.5 indicate evidence of antigenic exposure to the mucosa of the duodenum and allergic inflammation.

[Rengalin, a novel drug for treatment of cough in children. Intermediate data on multicentre, comparative randomized clinical trial].

UNLABELLED: Rengalin liquid formulation on the basis of antibodies to bradikinin histamine and morphine was specially designed for the treatment of cough in children. The three-component combination in therapeutically active against both dry and wet cough due to effect on diverse pathogenetic aspects of the cough reflex. The aim of the multicenter, comparative, randomized clinical trial was to estimate the efficacy and safety of rengalin in the treatment of cough in patients with acute respiratory infection (ARI) of the upper respiratory tract. METHODS: One hundred forty six patients at the age of 3 to 17 years (the average age of 8.2 ± 3.6 years) from 14 medical centres of Russia were observed. The patients suffered from dry/nonproductive, frequent, sore cough preventing from day-time activity and/or night sleep (≥ 4 by the Cough Severity Scale). The cough duration ranged from 12 hours to 3 days. For 3 days the patients of group 1 (n = 71) and group 2 (n = 75) were treated with rengalin and sinekod (butamirate) respectively. For the following 4 days the patients (in case of viscid expectoration were treated with ambroxole in the age doses. The results of the Per Protokol Analysis (n = 67 rengalin group and n = 73 sinekod group) with an account of the Non-Infectiority Design are presented. RESULTS: In 3 days the number of the group 1 patients with significant improvement/recovery by the day and night estimates amounted to 90% and 88% respectively (vs. 81% and 88% in the group 2 patients, no night opisodes of cough after 3-days rengalin use being recorded in 52% of the patients vs. 34% in the sinekod group patients (p = 0.0003). On the 7th day of the treatment with rengalin the number of the children with significant improvement of or recovery from day-time cought amounted to 99%and that of the patients with significant improvement of or recovery from night-time cough amounted to 93%, in 90% of them no night-time cough being recorded (p = 0.0008). As for the patients of the reference group, the respective values were 93% and 90%, no night-time cough being recorded in 81% of the patients. The time required for development of productive/moist cough during the 3-day treatment course in the patients of both the group was the same (2.9 ± 0.3 days in the patients of group 1 and 2.9 ± 0.4 days in the group 2 patients. Moreover, in 34% of the rengalin dry cough became residual (as rare episode of tussiculation with scantly exudation). After 3-day course of the rengalin therapy, 66% of the patients was treated with ambroxole (versus 95% in sinecod group (p < 0.0001) based on comparative analysis and χ2 = 17.7, p > 0.0001 by the results of the frequency analysis). The total duration of cough in the patients of groups 1 and 2 was 6.5 ± 0.8 and 6.7 ± 0.7 days respectively (the comparability truth, p = 0.0001). The severity of the day-time cough by the area under the curve estimates for 7 days of the treatment in the rengalin group patients was equel to 14.3 ± 5.6 numbers--days and that of the patients of the sinekod? group was equal to 15.9?6.1 numbers - days. The severity of the night-time cough was equal to 4.2 ± 2.7 number--days respectively. In 2 patients (3%) treated with sinekod signs of ARI generalization was observed after the 3-day treatment (p > 0.0001). The research physicians-investigators (CGI-EL Scale) the combination of the anti- and protussive activities in one drug to be efficient and absolutely safe for the chilgren. The therapeutic efficacy in the patients of the rengalin group was higher in 3 days (2.1 ± 0.5 numbers) and even in 7 days (2.7 ± 0.5 numbers). The results value in the patients of the sinekod group being 1.8 ± 0.4 and 2.5 ± 0.6 numbers (one-wayANOVA for repeated estimates ANOVA: Visit - F(1/138) = 146, p < 0.0001, TREATMENT--F(1/138) = 9.0, p = 0.003). The factor of the side effects in the patients of the rengalin group was zero (no side effects due to the treatment were recorded in the patients), whereas in the patients treated with sinekod for 3 days the respective value was 0.1 ± 0.3 (true superiority of rengalin by the ANOVA data. TREATMENT--F(1/138) = 4.7, p = 0.03). The efficacy factor of the rengalin was also in its favour (ANOVA: Visit--F(1/138) = 182, p < 0.0001, TREATMENT--F(1y138) = 7.3, p = 0.008). In the patients treated with rengalin there were defected no deviations in the biochemical and general clinical analyses of blood and urine, no adverse reactions characteristic of antitussive drugs of the action. 100-percent adherence to the therapy was stated. CONCLUSION: He antitussive effect of rengalin in the treatment of frequent dry day-time and night-time cough was observed earlier and proved to be comparable with that of butamirate (sinekod). Rengalin prevented significant exudation and viscid expectoration in many patients, promoted rapid residual in the patients with dry cough and the patients recovery. The use of rengalin for 3 days significantly lowered the percentage of the patients requiring treatment with mucolytics at the subsequent stages of ARI.

[Ergoferon liquid dosage form--efficacious and safe treatment for childhood acute respiratory infections. Interim outcomes of a multi-center, randomized, double-blind, placebo-controlled clinical trial].

The pediatric dosage form of Egroferon--a drug indicated for the treatment of influenza and acute respiratory infections (ARIs)--is developed taking in account the broad range of pathogens (most of which are viruses), and age-dependent features of immune system reactions (absence of specific immunity and immunological memory, relative "immaturity" of immune reactions, reduced interferon production by immunocompetent cells, etc.). Ergoferon interferes with the non-specific mechanisms of antiviral defence that ensure eliciting of an immune response, regardless of the virus type (the interferon system and CD4+cells), and influences virus-induced histamine release and histamine-mediated inflammatory reactions. Used over four years in clinical practice, the drug has shown a high efficacy and safety profile for the treatment of influenza and ARIs in adult patients. The purpose of the multi-center, randomized, double-blind, placebo-controlled study was to evaluate the clinical efficacy and safety of a new ergoferon liquid dosage form in the treatment of ARIs in children. The publication contains the results of the fist study stage completed as per the study plan and data from the interim analysis. METHODS. The screening involved a total of 162 subjects, aged 3 to 17 years (average, 8.2 ± 3.9 years), that had presented to 13 research centers based in Russia with common signs and symptoms of ARI (body temperature ≥ 38.0 degrees C, as measured with a digital infrared temporal artery thermometer; symptom severity score ≥ 4) during seasonal morbidity. Ergoferon was administered in 82 subjects receiving the therapeutic regimen of the drug for 5 days; 80 children received placebo. The subjects were monitored for 6 days. Treatment efficacy was assessed on the basis of morning, evening and total daily ARI symptom scores, including scoring estimates of fever, general symptoms and symptoms affecting the nose, throat and chest. Along with this, calculations were performed to obtain the Total Index (TI) of ARI; illness severity was evaluated using a mathematical "area under the curve" model. RESULTS. Starting from Day 2, the percentage of convalescents was observed to increase--from 6% (morning) and 14% (evening) to 20% and 29% on Day 3, respectively, and 58% and 61% on Day 4. The results suggested a substantially higher efficacy of Ergoferon as compared to placebo treatment (the Cochran-Mantel-Haenszel χ2 test: χ2 = 21.7; p < 0.0001). Ergoferon had a marked effect on fever and other signs of intoxication. In Ergoferon group, the percentage of non-fever subjects, with the endpoint defined at ≤ 37.2 degrees C, was 43% on Day 2, as estimated in the morning and the evening (vs 25% and 19% in the placebo group, respectively; χ2 = 10.6; p = 0.012), and 83% in the morning and 84% in the evening on Day 3 (vs 60% and 54% in the placebo group, respectively; χ2 = 16.7; p = 0.001). The Generalized Linear Model (GENMOD) procedure confirmed the significance of differences between the Ergoferon and placebo groups according to the following parameters: 1) Ergoferon was significantly more effective in reducing body temperature (to lower values) than the placebo; 2) Ergoferon had an earlier effect on fever (main marker of viremia), as compared to placebo; 3) The significant Ergoferon's superiority over placebo was also evident by the morning and evening measurements throughout the five-day therapy. The TI was observed to significantly decrease starting from Day 2 of Ergoferon administration: from 13.0 ± 4.5 to 7.9 ± 4.8 on Day 2 and 4.5 ± 2.9 on Day 3 (based on the patient's diary data); from 14.3 ± 4.2 to 4.9 ± 3.0 on Day 3 (based on the doctor's assessment). The severity of ARI-related intoxication signs was reduced most significantly, in particular as indicated by the results of doctor's objective examination on Day 3 (GENMOD: factor "Treatment"--χ2 = 147.8; p < 0.0001; factor "Day of administration"--X>=6.1; p = 0.013; Tukey-Kramer post hoc analysis: z = -3.09; p = 0.024). The average fever duration in ergoferon-treated subjects was 1.9 ± 0.8 days (p < 0.0001). The overall duration of ARI was much shorter in Ergoferon group than in the group of placebo (p = 0.021). The "area under the curve" measure of TI in Ergoferon group was significantly lower as compared to Placebo group, both according to the patient's diary records (21.9 ± 10.9 TI x Days vs 28.0 ± 13.0 TI x Days; p < 0.002) and the doctor's examination (12.4 ± 4.7 vs 14.2 ± 5.2 TI x Days; p = 0.023). Ergoferon treatment was associated with a lower frequency of using antipyretics (χ2 = 4.1; p = 0.043), particularly on the first day of illness. The monitoring of adverse events as well as the haematology, biochemistry and urinalysis findings were indicative of Ergoferon's safety. No signs of drug incompatibility were observed as a result of ergoferon administration in combination with antipyretics, decongestants, expectorants, inhaled corticosteroids, cromoglicic acid derivatives, leukotriene receptor antagonists, short-acting beta2 agonists and topical anti-septics. There were also no cases of bacterial complications, worsening of illness severity, or acute exacerbations of coexisting allergy or chronic ENT pathology. The children demonstrated good drug tolerance and 100% treatment compliance. CONCLUSIONS. Ergoferon liquid dosage form is an efficacious and safe treatment for ARIs in children. The study results demonstrated the drug's efficacy against the major syndromes associated and caused by viremia--fever and general intoxication. The early onset of the drug's effect was shown to result in a shorter time to convalescence and reduced ARI severity, particularly during the initial days of illness.

[Allergic reactions to cereals in children with atopy].

Cereals are the necessary and the major products in the diet. The aim of the study was to determine the dependence of frequency of sensitization to various cereals in children with atopy upon the age and diagnosis on the basis of anamnesis, the results of elimination diets, skin tests and the presence of specific IgE antibodies. 416 children and adolescents aged from 6 months to 17 years with atopic dermatitis (n = 359) and asthma (n = 57) has been investigated. The frequency of sensitization to cereals in children with atopic dermatitis according to skin tests ranged from 31 to 43%. Expressed sensitization (skin test +++, ++++) on the large majority of groats did not exceed 3% and only on corn and barley, it took place in 5.8 and 3.8%, respectively, while 81% of these children data coincided with a case history. The percentage of severe sensitization in boys was generally higher than that among girls. The percentage of pronounced sensitization to cereals increased with age in patients with atopy. The reason why the frequency of marked sensitization to maize in asthmatic children older than 7 years reached 20% and in children with atopic dermatitis reached 7.5% at the age of younger 1 year and 7.7% at the age from 3 to 7 years, remains unclear and requires further study.

[Topical issues of children's pulmonology in Russia].

Recent data illustrating the situation in children's pulmonology in this country are presented. Its main features are the high prevalence of acute and chronic lung diseases in children and the enhanced frequency of allergic pulmonary disorders, in the first place bronchial asthma. National guidelines on various aspects of the diagnosis and treatment of respiratory diseases in children need to be developed. Also important are their further in-depth studies. Training of specialists in children's pulmonoloy in conformity with the relevant international standards is considered to be a priority area of activity.

[Effects of hypoxic stimulation in experimental animals and in children with bronchial asthma]. / Effekty gipoksicheskoi stimuliatsii u zhivotnykh, nabliudaemye v éksperimente, i u detei, bolnykh bronkhialnoi astmoi.

Inhalations using hypoxic mixture of 12-15% O2 were tested in 40 rats (daily for 20 min. during 1-4 months) and in 200 children with light and mid-serious forms of bronchial asthma (for 5-10 min. 2-4 times with 5 min. break, course-10 days). Stimulation effect in animals was observed for 1-2 months and then depression came. The immunological and allergological indices were observed to distinctly improve, whereas the indices of the pulmonary function remained practically unchanged. The clinical indices in most patients improved and the similarity of this method and effects of other nonmedicamental methods was noted.