Effects of nebulized sildenafil on lung histology, oxygen saturation and blood gas parameters in chronic asthmatic BALB/C mice that attack was developed with methacoline<br><br>

Amaç: Sildenafil erektil disfonksiyon tedavisinde kullanılan bir fosfodiesteraz 5 inhibitörüdür. Fosfodiesteraz 5'in inhibisyonu siklik guanozin monofosfat düzeylerinde artışa neden olur. Siklik guanozin monofosfat ile astım patofizyolojisinde anahtar bir düzenleyici rol oynayan siklik adenozin monofosfatın benzer etkileri, siklik guanozin monofosfat yolu ile astım tedavisi için yeni ilaç geliştirme olasılığını arttırmaktadır. Bu çalışmada literatürde ilk kez metakolinle atak provoke edilen kronik astımlı farelerde nebulize sildenafili kullanmayı ve nebulize sildenafilin akciğer histolojisi, oksijen saturasyonları ve kan gazı parametreleri üzerine etkilerini araştırmayı amaçladık. Metotlar: Otuzbeş BALB/c fare her bir grupta 7 fare olacak şekilde 5 gruba ayrıldı (Grup 1-5). Grup 1 (kontrol) dışındaki tüm farelerde 74 gün boyunca ovalbumin uygulamaları ile kronik astım modeli oluşturuldu. Grup 2'ye başka bir ilaç verilmedi. Grup 3, 4 ve 5'teki farelerde çalışmanın 75. gününde metakolin inhalasyonları ile astım atağı oluşturuldu. Sonrasında nebulize sildenafil (0.07 mg/ml), nebulize budesonid (0.25mg/ml) ve nebulize salin sırası ile Grup 3, 4 ve 5'e verildi. Metakolin inhalasyonları öncesi ve sonrasında ve tedavilerden 15 dakika sonra farelerin kalp hızları ve oksijen saturasyonları ölçüldü. Tedavilerden bir saat sonra fareler anestezi sonrası kalplerinden kan alınarak sakrifiye edildi ve kan örnekleri kan gazı analizi için kullanıldı. Grup 1 ve 2'deki fareler de yine aynı metodla sakrifiye edildi. Tüm farelerin akciğer histolojileri ışık ve elektron mikroskopi ile incelendi. Bulgular: Grup 1'in bazal membran, düz kas ve epitel kalınlıkları, mast ve goblet hücre sayıları Grup 2'ninkilerden anlamlı olarak düşüktü (sırası ile p=0.000, p=0.000, p=0.000, p=0.001, p=0.000). Grup 3'ün bazal membran kalınlığı ve mast hücre sayısı, Grup 5'in bazal membran kalınlığı ve mast hücre sayısından anlamlı şekilde düşüktü (sırası ile p=0.000, p=0.001). Grup 5'in düz kas kalınlığı, Grup 3'ünkinden anlamlı olarak düşüktü (p=0.000). Grup 4'ün bazal membran kalınlığı ve mast hücre sayısı Grup 5'inkilerden anlamlı olarak düşüktü (sırası ile p=0.000, p=0.000). Grup 4'ün düz kas kalınlığı, Grup 3'ünkinden anlamlı şekilde düşüktü (p=0.000). Oksijen saturasyonları, kalp hızları ve kan gazı parametreleri tedavilere göre gruplar arasında farklılık göstermemekte idi. Sonuç: Sonuçlarımız kronik astım modelinin başarı ile oluşturulduğunu göstermektedir. Nebulize sildenafil plaseboya göre bazal membran kalınlığında ve mast hücre sayısında anlamlı azalma sağlamıştır. Nebulize budesonid sadece düz kas kalınlığını nebulize sildenafile göre anlamlı olarak azaltmıştır bunun dışında tüm parametreler iki grup arasında benzerdir. Her üç tedavi de farelerin kalp hızı, oksijen saturasyonu ve kan gazı parametreleri arasında farklılık meydana getirmemiştir. Nebulize sildenafilin akut astım tedavisindeki etkinliğini göstermek için daha ileri çalışmalara ihtiyaç vardır. Objective: Sildenafil is a phosphodiesterase 5 inhibitor, which is used for the treatment of erectile dysfunction. The inhibition of phosphodiesterase 5 leads to an increase in cyclic guanosine monophosphate levels. Similar activities of cyclic guanosine monophosphate and cyclic adenosine monophosphate that plays a key regulatory role in the pathophysiology of asthma, raise the possibility of a new drug development for the treatment of asthma via cyclic guanosine monophosphate way. In this study, we aimed to use the nebulized sildenafil in chronic asthmatic mice in which an attack was provoked by methacoline and investigate the effects of sildenafil on lung histology, oxygen saturation and blood gas parameters for the first time in the literature. Methods: Thirty five BALB/c mice were divided into 5 groups each containing 7 mice (Group 1-5). In all mice, except Group 1 (control), the model of chronic asthma was established with ovalbumin administrations during 74 days. No other drug was given to Group 2. In Group 3, 4 and 5, asthma attack was developed by methacoline inhalations on day 75. After methacoline inhalationsæ nebulized sildenafil (0.07 mg/ml), nebulized budesonide (0.25mg/ml) and nebulized saline were given to Group 3, 4 and 5, respectively. Heart rates and oxygen saturations were measured before and after the methacoline inhalations and 15 minutes after the treatments. One hour after the treatments, mice were sacrificed after anesthesia by blood suction from the hearts and the blood samples were used for blood gas analysis. The mice in Group 1 and 2 were also sacrificed by the same method. Lung histologies of all mice were examined by light and electron microscopies. Results: Basement membrane, subepithelial smooth muscle layer, and epithelium thicknesses as well as numbers of mast cells and goblet cells were significantly lower in Group 1 than in Group 2 (respectively p=0.000, p=0.000, p=0.000, p=0.001, p=0.000). Basement membrane thickness and number of mast cells were significantly lower in Group 3 than in Group 5 (respectively p=0.000, p=0.001). Subepithelial smooth muscle layer thickness was significantly lower in Group 5 than in Group 3 (p=0.000). Basement membrane thickness and number of mast cells were significantly lower in Group 4 than in Group 5 (respectively p=0.000, p=0.000). Subepithelial smooth muscle layer thickness was significantly lower in Group 4 than in Group 3 (p=0.000). Oxygen saturations, heart rates, and blood gas parameters did not show difference between groups according to the treatments. Conclusion: Our results show that the model of chronic asthma was successfully established. Nebulized sildenafil decreased basement membrane thickness and number of mast cells significantly compared to placebo. Nebulized budesonide decreased only subepithelial smooth muscle layer thickness more than nebulized sildenafil, otherwise all the parameters were similar between the two groups. All the three therapies did not make difference in heart rates, oxygen saturations and blood gas parameters of mice. Further studies are needed to show the efficacy of nebulized sildenafil in the treatment of acute asthma

Anaphylaxis Developoing after Measles Vaccine in an Infant with Cow's Milk Allergy

WOS: 000452049900009Cow's milk allergy is the most common food allergy in children. Casein, whey, alpha-lactalbumin, beta-lactoglobulin and bovine gamma-globulin are the best known allergens in cow's milk. Herein, we present an infant who was diagnosed with severe cow's milk allergy, followed-up with an elimination diet, and experienced a life-threatening severe anaphylaxis after live attenuated measles vaccine containing alpha-lactalbumin hydrolysate. high levels of immunoglobulin E (IgE) antibodics were determined by specific IgE analysis and the sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) method. It might be dangerous to administer live attenuated measles vaccine to children diagnosed with cow's milk allergy or to children suspected of being highly sensitive to cow's milk proteins

Solunum yolu allerjik hastalığı olan ergenlerin ve ailelerinin psikolojik durumları

Amaç: Çalışmanın amacı solunum yolu allerjileri olan adölesanların ve ailelerinin psikolojik durumlarının değerlendirilmesidir.Gereç ve Yöntemler: Çocuk ve adölesan psikiyatristleri adölesanların psikiyatrik durumlarını Çocuklar için Depresyon Ölçeği (CDI) ve Çocuk ve Ergenlerde Anksiyete ve İlgili Bozukluklar için Tarama ve Değerlendirme Ölçeği (SCARED) ile değerlendirdi. Psikiyatristler ailelerin psikolojik durumlarını Hamilton Depresyon Değerlendirme Ölçeği (HAM-D) ve Hamilton Aksiyete Değerlendirme Ölçeği (HAM-A) ile değerlendirdi. Bulgular: Anksiyete semptomları hastaların 63'ünden 21'inde saptandı. CDI skorları kontrollerde hastalara göre yüksekti (p=0,03). HAM-D skorları allerjik rinit ve eşlik eden astımı olan adölesanların ailelerinde kontrollere göre yüksekti (p=0,025). Hiçbir skor astım ve allerjik rinitin ağırlığından, astım kontrol düzeyinden, son bir yıl içindeki astım atak varlığından ve akciğer fonksiyon testlerinden etkilenmedi (p>0,05). SCARED ve CDI arasında orta düzeyde (r=0,644, p<0,001), HAM-A ve HAM-D skorları arasında yüksek düzeyde pozitif korelasyon saptandı (r=0,860, p<0,001).Sonuç: Aksiyete semptomların hastaların üçte birinde görüldü. HAM-D skorları allerjik rinit ve eşlik eden astımı olan adölesanların ailelerinde kontrollere göre yüksekti.Objective: The aim of the study was to evaluate the psychological status of adolescents with respiratory allergies and their caregivers.Materials and Methods: Child and adolescent psychiatrists evaluated the adolescents' psychological status using the Children's Depression Inventory (CDI) and Screen for Child Anxiety-Related Emotional Disorders (SCARED). Psychiatrist evaluated the psychological status of their caregivers using the Hamilton Depression Scale (HAM-D) and the Hamilton Anxiety Scale (HAM-A).Results: Anxiety symptoms were found in 21 of 63 patients. CDI scores were higher in controls than in patients (p=0.03). HAM-D scores were higher in the caregivers of adolescents with allergic rhinitis and comorbid asthma than in those of controls (p=0.025). None of the scores were affected by the severity of asthma and allergic rhinitis, asthma control levels, presence of an asthma attack in the preceding year as well as by pulmonary function tests (p&gt;0.05). Moderate and strong positive correlations were found between SCARED and CDI (r=0.644, p&lt;0.001) and HAM-A and HAM-D scores (r=0.860, p&lt;0.001).Conclusion: Anxiety symptoms were found in one-third of the patients. HAM-D scores were higher in the caregivers of adolescents with allergic rhinitis and comorbid asthma than in those of controls

Characteristics of children with positive tuberculin skin test Tüberkülin cilt testi pozitif saptanan çocukların özellikleri

The aim of the study was to define the characteristics of children with latent tuberculosis diagnosed with positive tuberculin skin test (TST) and evaluate potential risk factors in children with positive TST. Children followed with the diagnosis of latent tuberculosis infection were included in the study retrospectively. Demographic characteristics of patients including history of atopy, respiratory infections, family history of tuberculosis and atopy, number of BCG vaccinations, findings of physical examination and laboratory data were extracted from patient's file. Eighty-one children (51 male, 30 female) who had positive TST were retrospectively evaluated in the study. Mean age of the patients was 8.00 ± 4.00 years. Only 13 (16%) of the children had contact with a case who had active tuberculosis. It was shown that the age of the patients, number of BCG scars and BCG vaccination significantly affected TST reaction size. TST size was not affected with time passed after last dose of BCG vaccination, family history of tuberculosis, presence of TST positive case in the family, exposure to cigarette smoke, number of household family members and presence of respiratory allergic disease. The patient's age, numbers of BCG vaccination and BCG scars significantly affect TST results in childhood. This may cause difficulty in diagnosing latent tuberculosis infection and in decision of initiating prophylactic treatment. The results of this study may show that recently developed, more accurate and convenient in vitro tests that they have higher costs and require sophisticated laboratory, can be used to diagnose latent tuberculosis

Does Mean Platelet Volume in Children with Bronchiectasis Predict Exacerbations?

Bronchiectasis is a parenchymal lung disease which develops as a consequence of chronic inflammation and recurrent pulmonary infections. It is known that platelets have a role in inflammation and progressive pulmonary damage. Mean platelet volume (MPV) values as a marker of platelet activation, and might be used as an indicator of inflammation. Eighty-one children with the diagnosis of bronchiectasis followed between July 2010-July 2012 were enrolled in the study. The demographical data of patients were recorded and complete blood count (CBC) and MPV values were screened via hospital patient database. Complete blood count and MPV values were compared to age and sex-matched healthy children's data. In addition, CBC and MPV values were compared among chronic disease period without any exacerbation and exacerbation period in the children with bronchiectasis. The study was consisted of 81 children with bronchiectasis and 79 healthy controls. There was no significant difference between MPV values of non-exacerbation period and control group (p>0,05). Mean platelet volumes during acute exacerbation were significantly lower when compared with the values of non-exacerbation period and controls (p=0,02 and p=0,01 respectively). MPV and platelet counts (r=-0,502, p=0,01) as well as leucocyte count and hemoglobin levels were inversely correlated with each other in exacerbation period (r=-439, p=0.00). Mean platelet volume measured at during acute exacerbation were significantly decreased in children with bronchiectasis. With the result of present study, we suggest that MPV might be used as a predictor marker for diagnosis of acute exacerbations in children with bronchiectasis

Effects of nebulized sildenafil on lung histology, oxygen saturation and blood gas parameters in asthma attack of BALB/c mice Asti{dotless}m ataǧi{dotless}ndaki BALB/c farelerde nebulize sildenafilin akciǧer histolojisi, oksijen saturasyonu ve kan gazi{dotless} parametreleri üzerine etkileri

Objective: Sildenafil is a phosphodiesterase 5 inhibitor which is used for the treatment of erectile dysfunction. Inhibition of phosphodiesterase 5 promotes alveolar growth and angiogenesis, and attenuates inflammation and airway reactivity in animal models. We aimed to investigate the effects of nebulized sildenafil in asthma attack. Material and Methods: In all mice, except Group 1 (control), chronic asthma was established with repeated intraperitonal and aerosolized ovalbumin administrations. In three groups of chronic asthmatics (Group 3, 4 and 5), asthma attack was developed with increasing doses of methacoline inhalation. Afterwards,s nebulized sildenafil (0.07 mg/ml), nebulized budesonide (0.25mg/ml) and nebulized saline were given to Group 3, 4 and 5, respectively. Group 1 and Group 2 were not treated with either methacholine or nebulized therapies. Heart rates and oxygen saturations were measured. Blood gas analyses were performed and lung histologies were examined by light and electron microscopies. Results: Thicknesses of basement membrane, subepithelial smooth muscle layer and epithelium and numbers of mast and goblet cells were significantly lower in control group (Group 1) compared to the chronic asthmatics (Group 2) (p<0.001, p=0.002, p=0.001, p<0.001, p<0.001, respectively). These results suggested that the model of chronic asthma was successfully established. Numbers of mast cells were significantly lower in sildenafil group compared to the saline group (p=0.020). Oxygen saturation, heart rate, and blood gas parameters did not show differences between the treatment groups. Conclusion: Nebulized sildenafil significantly decreased the numbers of mast cells compared to placebo. Nevertheless, nebulized sildenafil was nor effective on oxygen saturation, heart rate, and blood gas parameters. © 2013 by Türkiye Klinikleri

Neopterin Levels And Indoleamine 2,3-Dioxygenase Activity As Biomarkers Of Immune System Activation And Childhood Allergic Diseases

Background Although Th2 immune activation is predominant in allergic diseases, neopterinlevels and indoleamine 2,3-dioxygenase (IDO)-1 activity (kynurenine:tryptophan ratio), which reflect Th1 immune activity, increase with interferon-gamma (IFN-γ) stimulation. We investigated neopterin, tryptophan, and kynurenine levels as biomarkersof the Th1 immune system activation and changes in IDO-1 activityin children with asthma, allergic rhinitis, and atopic dermatitis, as well as the relationship between these biomarkers and the total IgE level, age, and disease severity. Methods We divided 205 children (80 girls and 125 boys, four months to 17 years old) into four groups: controls, patients with asthma, patients with allergic rhinitis, and patients with atopic dermatitis. Peripheral venous blood samples were collected. Neopterin levels were determined by an enzyme immunoassay. Tryptophan and kynurenine levels were analyzed using HPLC. IDO-1 enzyme activity was calculated using tryptophan and kynurenine levels. IgE levels were measured. The Mann-Whitney U test, Kruskal-Wallis test, and Conover post-hoc method were used for statistical analysis. Results Neopterin, tryptophan, and kynurenine levels were higher and IgE levels and IDO-1 enzyme activity were lower in patients with asthma and allergic rhinitis than in controls (P<0.05). Patients with atopic dermatitis showed higher neopterin, tryptophan, and kynurenine levels, higher IDO-1 activity, and lower IgE levels thancontrols (P<0.05). Conclusions The Th1/Th2 balance is disrupted in children with allergic diseases, concomitant with increased Th1-mediated immune response activation and reduced IgEproduction, which is promoted by Th2-type cytokines.PubMedWoSScopu

Effects of Nebulized Sildenafil on Lung Histology, Oxygen Saturation and Blood Gas Parameters in Asthma Attack of BALB/c Mice

Objective: Sildenafil is a phosphodiesterase 5 inhibitor which is used for the treatment of erectile dysfunction. Inhibition of phosphodiesterase 5 promotes alveolar growth and angiogenesis, and attenuates inflammation and airway reactivity in animal models. We aimed to investigate the effects of nebulized sildenafil in asthma attack. Material and Methods: In all mice, except Group 1 (control), chronic asthma was established with repeated intraperitonal and aerosolized ovalbumin administrations. In three groups of chronic asthmatics (Group 3, 4 and 5), asthma attack was developed with increasing doses of methacoline inhalation. Afterwards,s nebulized sildenafil (0.07 mg/ml), nebulized budesonide (0.25mg/ml) and nebulized saline were given to Group 3, 4 and 5, respectively. Group 1 and Group 2 were not treated with either methacholine or nebulized therapies. Heart rates and oxygen saturations were measured. Blood gas analyses were performed and lung histologies were examined by light and electron microscopies. Results: Thicknesses of basement membrane, subepithelial smooth muscle layer and epithelium and numbers of mast and goblet cells were significantly lower in control group (Group 1) compared to the chronic asthmatics (Group 2) (p<0.001, p=0.002, p=0.001, p<0.001, p<0.001, respectively). These results suggested that the model of chronic asthma was successfully established. Numbers of mast cells were significantly lower in sildenafil group compared to the saline group (p=0.020). Oxygen saturation, heart rate, and blood gas parameters did not show differences between the treatment groups. Conclusion: Nebulized sildenafil significantly decreased the numbers of mast cells compared to placebo. Nevertheless, nebulized sildenafil was nor effective on oxygen saturation, heart rate, and blood gas parameters. © 2013 by Türkiye Klinikleri

Glycyrrhizin and Long-Term Histopathologic Changes in a Murine Model of Asthma

BACKGROUND: Licorice root has been widely used to treat bronchial asthma for many years. However, the effect of this herb on lung histopathologic features is not fully understood