Clinical and genetic associations of NO-synthase and arginase gene polymorphisms and gene-gene interactions in children with bronchial asthma

2020 ◽  
Vol 15 (5) ◽  
pp. 7-17
Author(s):  
B.Ts. Batozhargalova ◽  
◽  
Yu.L. Mizernitsky ◽  
S.E. Dyakova ◽  
N.V. Petrova ◽  
...  
Keyword(s):  
Bronchial Asthma ◽  
Gene Polymorphisms ◽  
Tandem Repeats ◽  
Inhaled Corticosteroids ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
N Gene ◽  
Gene Interactions ◽  
Exhaled Air ◽  
S Allele

Objective. To analyze the association between NOS1, NOS2, NOS3, ARG1, and ARG2 gene polymorphisms and clinical, laboratory, and functional characteristics of bronchial asthma (BA) in children by evaluating gene-gene interactions. Patients and methods. We have evaluated the associations between the NOSs and ARG genes and gene-gene interactions in 107 children with BA. We performed comparative genetic analysis of associations between polymorphic variants of candidate genes in 107 BA patients and clinical manifestations of the disease, laboratory, and functional parameters. Results. We have found an association between the short (S) allele and SS genotype of the NOS1 (AAT)n gene and early disease onset (<5 years), severe BA, and antiinflammatory targeted therapy (with omalizumab and combination inhaled corticosteroids with long-acting β2-agonists). We have also revealed an association between the short (S) allele and SS genotype of the NOS1 (AAT)n gene, as well as long (L) alleles and LL genotypes of the NOS2A (CCTTT)n gene in BA patients and elevated FeNO levels in the exhaled air. The following association have also been identified: between alleles and genotypes containing long (L) tandem repeats in the NOS2A (CCTTT)n gene and reduced FEV1; between AG genotype of the ARG2 gene (rs3742879), alleles and genotypes containing long tandem repeats (L) of the NOS2А (CCTTT)n gene and reduced FEV1/ FVC; between alleles and genotypes containing long tandem repeats (L), combinations of genotypes SL+LL of the NOS2А (CCTTT)n and impaired patency at the level of the middle bronchi FEF50; between allele G, heterozygous genotype AG of the ARG2 (rs3742879) gene with impaired patency at the level of peripheral bronchi FEF75. Conclusion. Our analysis of gene-gene interactions has demonstrated phenotypic characteristics of BA: early BA onset, severe BA, decreased FEV1 and FEF50, increased NO concentration in exhaled air, and presence of fungal and epidermal sensitization. Key words: children, bronchial asthma, NOS and ARG gene polymorphisms, gene-gene interactions

scholarly journals Association of polymorphisms of NO synthases and arginase genes, clinical, laboratory and functional indicators with the level of nitrogen oxide in exhaled air in children with bronchial asthma

2019 ◽  
Vol 64 (5) ◽  
pp. 55-68
Author(s):  
B. T. Batozhargalova ◽  
S. E. Diakova ◽  
N. V. Petrova ◽  
Yu. L. Mizernitsky ◽  
R. A. Zinchenko
Keyword(s):  
Nitrogen Oxide ◽  
Bronchial Asthma ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Clinical Laboratory ◽  
N Gene ◽  
Homozygous Genotype ◽  
Exhaled Air ◽  
Short Tandem ◽  
Fungal Sensitization

The article presents the results of a study of the associations of NO synthase and arginase genes in children with bronchial asthma with clinical, laboratory and functional parameters depending on the level of nitrogen oxide in exhaled air (FeNO). We examined 107 children with bronchial asthma, they were divided into 2 groups depending on the level of FeNO. We found a number of associations in the group of patients with an elevated level of FeNO (≥20 ppb): carriage of alleles and genotypes containing short tandem repeats of S (9–11) NOS1(AAT)n gene, with an early debut and severe course of the disease, an increased level of total IgE in blood serum; carriage of alleles and genotypes containing long tandem repeats L (12–16) of the NOS2A(CCTTT) n gene, with a moderate course of the disease, with an increased level of IgE; carriage of the allele *A of the ARGII gene (rs3742879) with a moderate course of the disease; carriage of the *G allele and heterozygous *AG genotype of the ARGII gene (rs3742879) with a decreased level of FEV1/FVC; carriage of L alleles and a combination of the SL and LL genotypes of the NOS1(AAT)n gene with elevated blood eosinophils (eosinophilia); a combination of S/L + L/L genotypes of the NOS1(AAT)n gene with fungal sensitization. The authors established the correlations between disease severity and NOS1(AAT)n; the age of the manifestation of the disease and NOS1(AAT)n; FEV1/FVC and ARGII (rs3742879); feedback between blood eosinophilia and NOS1(AAT)n. The authors also determined a number of associations in the group of patients with low level of FeNO (<20 ppb): carriage of alleles and genotypes containing short tandem repeats of S (9–11) gene NOS1(AAT)n, with fungal sensitization; carriage of alleles and genotypes containing long tandem repeats of L (12–16) gene NOS2A(CCTTT)n, with reduced FEV1 and FEV1/FVC; carriage of the homozygous genotype of *GG gene ARGII(rs3742879) with epidermal sensitization. With a reduced level of FeNO, the study determined a relationship between the severity of bronchial asthma and NOS1(AAT)n; degree of effectiveness of anti-inflammatory basic therapy and NOS1(AAT)n; fungal sensitization and NOS1(AAT)n; feedback between FEV1 and NOS2(CCTTT)n; FEV1/FVC and NOS2(CCTTT)n.

scholarly journals CHANGES IN BRONCHIAL ASTHMA CONTROL AND INFLAMMATION BIOMARKERS DURING THE ALLERGEN-SPECIFIC IMMUNOTHERAPY AND ACCOMPANYINGTREATMENT

2011 ◽  
Vol 8 (2) ◽  
pp. 44-50
Author(s):  
T I Eliseeva ◽  
Yu S Kul'gina ◽  
I I Balabolkin ◽  
T I Eliseeva ◽  
U S Kulgina ◽  
...  
Keyword(s):  
Asthma Control ◽  
Bronchial Asthma ◽  
Specific Immunotherapy ◽  
Inhaled Corticosteroids ◽  
Total Concentration ◽  
Allergic Inflammation ◽  
Exhaled Breath ◽  
Allergen Specific Immunotherapy ◽  
Exhaled Air ◽  
Ic Treatment

Background. The work is devoted to the studying of the correspondence between the symptoms dynamics and the concentrations of the nitrogen oxide (NO) methabolites in the exhaled breath air condensate in patients with bronchial asthma (BA) during allergenospecific immunotherapy (ASIT) and accompanying treatment. Methods. The symptoms of BA were estimated using the Asthma Control Questionaire (ACQ). The inflammation biomarkers level (NO methabolites in the exhaled air condensate) was measured by the spectrofluorometric method of Griess. Results. During ASIT and accompanying treatment (cetirizine or levocetirizine with basis BA therapy corresponding to the observed BA severity with allergens eliminated), the symptoms reduction (decrease in the total ACQ scores) was observed along with decrease of the total concentration of NO metabolites in blood. This was observed both for the steroid- naive patients and for the patients taking the inhaled corticosteroids (IC) treatment. Conclusion: In patients with mild BA, combination of ASIT and non-steroid accompanying therapy on the basis of cetirizine or levocetirizine results in the improvement of the BA control and reduction of the allergic inflammation in airways comaparable to the analogous processes in patients with moderate BA taking the analogous therapy but with IC included.

CLINICAL AND SPIROGRAPHIC FEATURES OF BRONCHIAL ASTHMA IN SCHOOLCHILDREN DEPENDING ON THE DIFFERENT REGIMENS OF BASIC ANTI-INFLAMMATORY THERAPY

2020 ◽  
Vol 73 (1) ◽  
Author(s):  
Olena Koloskova ◽  
Tetiana Bilous ◽  
Galyna Bilyk ◽  
Kristina Buryniuk-Glovyak ◽  
Olena Korotun ◽  
...  
Keyword(s):  
Bronchial Asthma ◽  
Inhaled Corticosteroids ◽  
Persistent Asthma ◽  
High Specificity ◽  
Clinical Feature ◽  
Clinical Group ◽  
Comparison Groups ◽  
Anti Inflammatory ◽  
High Doses ◽  
Persistent Bronchial Asthma

The aim: To study the clinical and spirographic features persistence of the bronchial asthma in schoolchildren against the background of the alternative daily doses of inhaled corticosteroids to increase the effectiveness of anti-inflammatory therapy for this disease. Materials and methods: A complete comprehensive clinical-paraclinical examination of 65 schoolchildren with persistent asthma was conducted. According to the average daily dose of inhaled corticosteroids (ICS) the patients were divided into two clinical groups. The first (I) group consisted of 46 children who received ICS in the regimen of low-to-medium equipotent doses (253.95±9.98 μg per day), and the second (II) comparison group was formed of 19 patients who controlled the pBA using high doses of ICS (494.74±5.56 μg per day). Results: The patients of the І clinical group compared to patients of the ІІ group have a higher risk of the mild bronchial obstructive syndrome during asthma attacks. In assessing the level of control of persistent bronchial asthma using the CIA-scale, it was found that in II group cases of the controlled course of the disease were observed almost two times less than in children of the I group of comparison. In conducting spirography in children of comparison groups, it was shown that the ratio of indices of bronchospasm (FEV1/ FVC) was worse in patients receiving high doses of ICS. Conclusions: So, сharacteristic clinical feature of asthma controlled by high doses of ICS is more severe nature of bronchial obstructive syndrome during the period of exacerbation (OR=1.9-3.0). In the management of persistent bronchial asthma, the Gensler index which has high specificity (94.4%) and accuracy (92.2%) should be used for disease control verification.

Celiac Disease in Kosovar Albanian Children: Evaluation of Clinical Features and Diagnosis

2020 ◽  
Vol 16 (3) ◽  
pp. 241-247
Author(s):  
Atifete Ramosaj-Morina ◽  
Alije Keka-Sylaj ◽  
Arbana Baloku Zejnullahu ◽  
Lidvana Spahiu ◽  
Virgjina Hasbahta ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Gastrointestinal Symptoms ◽  
Dominant Mode ◽  
Primary School Children ◽  
Cross Sectional ◽  
Classical Form ◽  
Wide Range ◽  
The Mean

Background: Celiac disease is an immune-mediated disorder characterized by variable clinical manifestations, specific antibodies, HLA-DQ2/DQ8 haplotypes, and enteropathy. Objectives: The aim of this study was to present the clinical spectrum and patterns of celiac disease in Kosovar Albanian children. Methods: A cross-sectional retrospective study was performed with Albanian children aged 0-18 years, treated for celiac disease in the Pediatric Clinic, University Clinical Center of Kosovo from 2005 to 2016. Results: During the study period, 63 children were treated for celiac disease. The mean age at diagnosis was 5.5 years (SD ± 3.31). The mean age at celiac disease onset was 3.3 years (SD ± 2.02), while the mean delay from the first symptoms indicative of celiac disease to diagnosis was 2.2 years (SD ± 2.09). More than 70% of the patients were diagnosed in the first 7 years of life, mainly presented with gastrointestinal symptoms, while primary school children and adolescents mostly showed atypical symptoms (p<0.001). The classical form of celiac disease occurred in 78% of the cases. Sixty (95%) patients carried HLA-DQ2.5, DQ2.2 and/or HLA-DQ8 heterodimers, and only three of them tested negative. Conclusions: Kosovo, as the majority of developing countries, is still facing the classical form of celiac disease as the dominant mode of presentation; as a result, most children with other forms of the celiac disease remain undiagnosed. : Physicians should be aware of the wide range of clinical presentations and utilize low testing thresholds in order to prevent potential long-term problems associated with untreated celiac disease.

Vitiligo: An Updated Narrative Review

2020 ◽  
Vol 16 ◽  
Author(s):  
Alexander K. C. Leung ◽  
Joseph M. Lam ◽  
Kin Fon Leong ◽  
Kam Lun Hon
Keyword(s):  
Present Article ◽  
English Literature ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Calcineurin Inhibitors ◽  
Ultraviolet B ◽  
Lower Limbs ◽  
Treatment Modalities ◽  
Topical Corticosteroids ◽  
Topical Calcineurin Inhibitors

Background: Vitiligo is a relatively common acquired pigmentation disorder that can cause significant psychological stress and stigmatism. Objective: This article aims to familiarize physicians with the clinical manifestations, evaluation, diagnosis, and management of vitiligo. Methods: A Pubmed search was conducted in Clinical Queries using the key term "vitiligo". The search included metaanalyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to the English literature. The information retrieved from the above search was used in the compilation of the present article. The information retrieved from the above search was used in the compilation of the present article. Results: Approximately one quarter of patients with vitiligo have the onset before 10 years of age. Genetic, immunological, neurogenic and environmental factors may have a role to play in the pathogenesis. Vitiligo typically presents as acquired depigmented, well-demarcated macules/patches that appear milk- or chalk-white in color. Lesions tend to increase in number and enlarge centrifugally in size with time. Sites of predilection include the face, followed by the neck, lower limbs, trunk, and upper limbs. The clinical course is generally unpredictable. In children with fair skin, no active treatment is usually necessary other than the use of sunscreens and camouflage cosmetics. If treatment is preferred for cosmesis, topical corticosteroids, topical calcineurin inhibitors, and narrowband ultraviolet B phototherapy are the mainstays of treatment. Conclusion: The therapeutic effect of all the treatment modalities varies considerably from individual to individual. As such, treatment must be individualized. In general, the best treatment response is seen in younger patients, recent disease onset, darker skin types, and head and neck lesions. Topical corticosteroids and calcineurin inhibitors are the treatment of choice for those with localized disease. Topical calcineurin inhibitors are generally preferred for lesions on genitalia, intertriginous areas, face, and neck. Narrowband ultraviolet B phototherapy should be considered in patients who have widespread vitiligo or those with localized vitiligo associated with a significant impact on the quality of life who do not respond to treatment with topical corticosteroids and calcineurin inhibitors.

Adult systemic lupus erythematosus in Egypt: The nation-wide spectrum of 3661 patients and world-wide standpoint

Lupus ◽  
2021 ◽  
pp. 096120332110142
Author(s):  
Tamer A Gheita ◽  
Rasha Abdel Noor ◽  
Esam Abualfadl ◽  
Osama S Abousehly ◽  
Iman I El-Gazzar ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Age Of Onset ◽  
Wide Spectrum ◽  
Age At Onset ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Population Based ◽  
Systemic Lupus ◽  
Cross Sectional

Objective The aim of this study was to present the epidemiology, clinical manifestations and treatment pattern of systemic lupus erythematosus (SLE) in Egyptian patients over the country and compare the findings to large cohorts worldwide. Objectives were extended to focus on the age at onset and gender driven influence on the disease characteristics. Patients and method This population-based, multicenter, cross-sectional study included 3661 adult SLE patients from Egyptian rheumatology departments across the nation. Demographic, clinical, and therapeutic data were assessed for all patients. Results The study included 3661 patients; 3296 females and 365 males (9.03:1) and the median age was 30 years (17–79 years), disease duration 4 years (0–75 years) while the median age at disease onset was 25 years (4–75 years). The overall estimated prevalence of adult SLE in Egypt was 6.1/100,000 population (1.2/100,000 males and 11.3/100,000 females).There were 316 (8.6%) juvenile-onset (Jo-SLE) and 3345 adult-onset (Ao-SLE). Age at onset was highest in South and lowest in Cairo (p < 0.0001). Conclusion SLE in Egypt had a wide variety of clinical and immunological manifestations, with some similarities with that in other nations and differences within the same country. The clinical characteristics, autoantibodies and comorbidities are comparable between Ao-SLE and Jo-SLE. The frequency of various clinical and immunological manifestations varied between gender. Additional studies are needed to determine the underlying factors contributing to gender and age of onset differences.

scholarly journals SAT0507 CLINICAL CHARACTERISTICS AND TREATMENT RESPONSE IN JUVENILE GOUT PATIENTS: A SINGLE CENTER EXPERIENCE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1210.2-1210
Author(s):  
S. Zheng ◽  
P. Y. Lee ◽  
Y. Huang ◽  
Q. Huang ◽  
S. Chen ◽  
...  
Keyword(s):  
Renal Function ◽  
Uric Acid ◽  
Treatment Response ◽  
Serum Uric Acid ◽  
Clinical Characteristics ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Joint Involvement ◽  
Normal Body Mass Index ◽  
Finger Joints

Background:The incidence of juvenile gout is increasing in China. The clinical manifestations of juvenile gout and treatment strategies to reduce uric acid levels in children are not well described due to the limited number of cases in the past.Objectives:We aim to describe the clinical characteristic of children with gout and study the treatment response to febuxostat.Methods:These studies were approved by the Institutional Review Board of Guangdong Second provincial General Hospital. We performed a retrospective analysis on 98 juvenile gout patients (age ≤ 18 years) evaluated in our hospital from Jan 2016 to Dec 2019. We analyzed clinical parameters, laboratory data and treatment response.Results:The average age of disease onset in children with gout was 15.2 ± 2.0 years and the youngest patient was 9 years old. The majority of patients were male (94/98) and mean serum uric acid (sUA) level were 705.8 ± 145.7 μmol/L (reference range <420 μmol/L). More than half of the cohort had normal body mass index (mean 24.7 ± 4.7 kg/m2; range 14.9 to 36.1 kg/m2). Renal function was generally normal in these children (serum creatinine 96.9 ± 17.8 μmol/L). In terms of joint manifestations, juvenile gout preferentially affected finger joints (29%), ankles (28%) and metatarsal joints (MTP; 20%). The most frequent sites of initial gout attack were ankles (45%), MTP (39%) and fingers (6%). In addition, tophi can occur in pediatric patients and typically develop in the finger joints (54%). Tophi was observed in about 25% of juvenile gout patients, typically within the first two years of disease onset (mean duration 1.7 ± 0. 9 years). We have found tophi in children as young as 10 years of age.For treatment for chronic hyperuricemia, 32 patients (32.7%) were started on febuxostat and 5 patients (5.1%) received allopurinol. A decrease in sUA was observed in both groups after the first month of treatment (febuxostat: baseline 690.4 ± 99.7 μmol/L to 482.7 ± 140.8 μmol/L vs. allopurinol: baseline 728.8 ±112.8 μmol/L to 565.0 ± 116.7 μmol/L, P=0.477). Serum uric acid of 6 patients in the febuxostat group (none in the allopurinol group) dropped below 360 μmol/L. There were no statistical differences in Cr, AST and ALT between the groups. During follow-up after 3 months, further decline in sUA level were observed in patients treated with febuxostat (409.5 ± 83.4, compared with baseline P<0.001).Conclusion:Juvenile gout has a different pattern of joint involvement and is less associated with elevated BMI compared to gout in adults. We show that febuxostat is effective in reducing uric acid levels in juvenile gout. These findings will help clinicians better understand the clinical manifestations and treatment response in juvenile gout.Figure 1Compared treatment response with allopurinol and febuxostatReferences:[1]Kishimoto K, Kobayashi R, Hori D, et al. Febuxostat as a Prophylaxis for Tumor Lysis Syndrome in Children with Hematological Malignancies. Anticancer Res. 2017 Oct;37(10):5845-5849.[2]Lu, C.C., et al. Clinical characteristics of and relationship between metabolic components and renal function among patients with early-onset juvenile tophaceous gout. J Rheumatol, 2014. 41(9): p. 1878-83.Disclosure of Interests:None declared

scholarly journals Molecular detection and phylogenetic relationship of wild-type strains of canine distemper virus in symptomatic dogs from Uberlândia, Minas Gerais

2015 ◽  
Vol 67 (6) ◽  
pp. 1510-1518
Author(s):  
S.A. Headley ◽  
T.R. Santos ◽  
L. Bodnar ◽  
J.P.E. Saut ◽  
A.P. Silva ◽  
...  
Keyword(s):  
Canine Distemper Virus ◽  
Phylogenetic Analyses ◽  
Clinical Manifestations ◽  
N Gene ◽  
Clinical Samples ◽  
Canine Distemper ◽  
Wild Type ◽  
Age Related ◽  
Relationship Of ◽  
Type Strains

This study investigated the occurrence of canine distemper virus (CDV) by evaluating the presence of viral RNA within urine samples of dogs from Uberlândia, MG, with clinical manifestations suggestive of infection by CDV by targeting the CDV N gene. Of the clinical samples collected ( n =33), CDV viruria was detected in 45.5%. Five dogs died spontaneously; all had characteristic CDV-associated histopathological alterations and demonstrated CDV viruria. Statistical analyses revealed that the age, gender, breed, or the organ system of the dog affected had no influence on the occurrence of canine distemper. Myoclonus and motor incoordination were the most significant neurological manifestations observed. A direct association was observed between keratoconjunctivitis and dogs with CDV viruria. These findings suggest that CDV viruria in symptomatic dogs might not be age related, and that symptomatic dogs can demonstrate clinical manifestations attributed to CDV without viruria identified by RT-PCR. Additionally, the results of the sequence identities analysed have suggested that all Brazilian wild-type strains of CDV currently identified are closely related and probably originated from the same lineage of CDV. Nevertheless, phylogenetic analyses suggest that there are different clusters of wild-type strains of CDV circulating within urban canine populations in Brazil.

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