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ABSTRACT: BACKGROUND: Increased arginase activity in the airways induces reduced bioavailability of l-arginine and cause deficiency of bronchodilatating and anti-inflammatory nitric oxide (NO). Therefore, arginine and arginase inhibitors may have therapeutic potential in the treatment of asthma. Using a murine model of asthma, we aimed to investigate the effects of inhaled l-arginine and arginase inhibitor Nω-hydroxy-nor-l-arginine (nor-NOHA) and co-treatment on airway histology of asthmatic lung tissue. METHODS: Forty-two BALB/c mice were divided into six groups: I (control), II (placebo), III, IV, V and VI. All mice except for control group were sensitised by an intraperitoneal injection of ovalbumin with alum adjuvant and then challenged with an aerosol of ovalbumin on three days of the week for eight weeks beginning from the 21st day of the study. Lung histology and bronchoalveolar lavage cell (BAL) counts were evaluated after treatment with inhaled l-arginine, nor-NOHA, l-arginine-nor-NOHA combination, budesonide and placebo. Interleukin(IL)-4 and IL-5 levels are determined in lung homogenates with ELISA. RESULTS: l-Arginine group was similar to budesonide group in lowering all histological parameters. Results of groups treated with nor-NOHA were also similar to budesonide group except for epithelial thickness. The number of eosinophils in BAL decreased significantly in groups receiving study drugs. Decrease was only noted in IL-4 levels in group receiving nor-NOHA. CONCLUSION: We demonstrated that inhaled l-arginine administration alleviated all histological parameters similar to budesonide and treatment with arginase inhibitor improved not all but some of the pathological changes in chronic asthma. Combination therapy had no additive effect on either treatment.
Allergologia et Immunopathologia 04/2013; · 1.04 Impact Factor
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ABSTRACT: BACKGROUND: Polymorphisms of plasminogen activator inhibitor-1 (PAI-1) and angiotensin-converting enzyme (ACE) genes have been implicated in susceptibility to asthma. In this study, we aimed to investigate whether there was any association between childhood asthma and polymorphisms of the PAI-1 and ACE genes. METHODS: Two hundred and three Turkish children aged 5-15 years, including 102 asthmatic patients and 101 healthy control subjects were included in this study. The asthma group was divided into two groups as follows: Group I: Asthmatic children with positive family history for atopy (n=53), Group II: Asthmatic children without any family history for atopy (n=49). One hundred and twenty-eight atopic family members were also included in the study. The insertion/deletion (I/D) polymorphism of the ACE and PAI-1 4G/5G gene polymorphisms was carried out by polymerase chain reaction. RESULTS: The prevalence of the PAI-1 4G allele was significantly greater in asthmatic children compared to control group (p<0.05, OR: 1.64 (1.11-2.43)) but there was no significant relation between ACE I/D genotypes and childhood asthma. No significant difference was detected between Groups I and II in terms of these ACE and PAI-1 genotypes and allele frequencies. No significant relationship was found between both gene polymorphisms and total serum IgE and skin prick test results. CONCLUSION: It has been established that PAI-1 4G allele may be a genetic risk factor for childhood asthma but ACE gene I/D polymorphisms do not play a role in the development of asthma in the sample of Turkish children.
Allergologia et Immunopathologia 02/2012; · 1.04 Impact Factor
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ABSTRACT: Curcumin, a dietary pigment responsible for the yellow colour of curry, has been used for the treatment of inflammatory diseases and exhibits a variety of pharmacological effects.
Forty-two BALB/c mice were divided into six groups: I, II, III, IV, V, and control group. All groups except the controls were sensitised and challenged with ovalbumin. Group I received nebulised saline in challenge period. Mice in groups II, III, IV, and V were administered curcumin at a dose of 10 mg/kg, curcumin 20 mg/kg, dexamethasone 1 mg/kg, and dimethyl sulfoxide 1 mg/kg, respectively, intraperitoneally once a day for the final 5 days of the challenge period. Animals were sacrificed 24 h after the last drug administration and the airway samples were evaluated histologically by light microscopy.
All histological parameters in Group III improved similar to Group IV when compared to Group I. In Group II, only thickness of epithelium was significantly lower compared with regard to Group I. All variables except epithelium thicknesses were found to be significantly better in Group III compared to Group II.
In our study, we demonstrated that curcumin administration alleviates the pathological changes of chronic asthma. Curcumin might be a promising therapy for asthma in the future.
Allergologia et Immunopathologia 08/2011; 40(4):210-4. · 1.04 Impact Factor
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ABSTRACT: Asthma is the most common chronic disease of childhood in industrialised countries. T helper-2 (Th-2) cells, mast cells and eosinophils have a role in inflammation of asthma. Recently it was shown that platelets also play a role in asthma. Mean platelet volume shows platelet size and reflects platelet activation.
The aim of this retrospective study is to evaluate levels of mean platelet volume in asthmatic patients during asymptomatic periods and exacerbations compared with healthy controls.
The study consisted of 100 asthmatic patients (male/female: 55/45, mean age: 8.2±3.3) and 49 age and sex matched healthy children as a control group.
Mean platelet volume values of asthmatic patients during asymptomatic period were 7.7±0.8fL while mean platelet volume values in asthmatics during exacerbation were 7.8±0.9fL. Comparison of mean platelet volume values of asthmatic patients and healthy controls both in acute asthmatic attack and asymptomatic period showed no difference (p>0.05). Comparison of mean platelet volume values at asthmatic attack and asymptomatic period also had no difference (p>0.05). The presence of atopy, infection, eosinophilia, elevated immunoglobulin E, and severity of acute asthmatic attack did not influence mean platelet volume values.
The results of our study suggest that mean platelet volume values may not be used as a marker in bronchial asthma, although prospective studies with larger number of patients are needed to evaluate the role of mean platelet volume in asthma.
Allergologia et Immunopathologia 05/2011; 40(2):104-7. · 1.04 Impact Factor
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ABSTRACT: Erythropoietin (EPO) is originally defined as a haematopoietic growth factor, but also has anti-inflammatory effects through cytokine modulation. This anti-inflammatory and cytokine modulating effect has not been investigated for the treatment of asthma. We aimed to determine the beneficial effects of erythropoietin on lung histology of murine model of chronic asthma.
Thirty-five BALB/c mice were divided into five groups: I; II; III; IV; and control group. All groups except control group were sensitised and challenged with ovalbumin. Mice with experimentally induced asthma in Group I received saline; Group II EPO 500IU/kg; Group III EPO 1000IU/kg; and Group IV dexamethasone 1mg/kg intraperitoneally once a day in the last five days of the challenge period. Animals were sacrificed 24h after the last administration of study drugs. Histological findings of airways were evaluated by light and electron microscopic examination.
All histological parameters of asthma in the group treated with a high dose of EPO (Group III) were significantly ameliorated when compared with the group treated with saline (Group I). In comparison to the group treated with low dose of EPO (Group II) and the group treated with saline (Group I), basement membrane thicknesses and number of mast cells were significantly lower in the group treated with low dose of EPO (Group II). All histological parameters were similar between the group treated with high dose of EPO (Group III) and the group treated with dexamethasone (Group IV) except higher number of mast cells in the group treated with high dose of EPO (Group III). Additionally, the results of all histological parameters in the group treated with high dose of EPO (Group III) were significantly better when compared with the group treated with low dose of EPO (Group II).
We found that EPO ameliorated histological changes of chronic murine model of asthma. Further studies are needed to evaluate the efficacy of EPO in the treatment of asthma.
Allergologia et Immunopathologia 05/2011; 40(2):75-80. · 1.04 Impact Factor
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Allergologia et Immunopathologia 01/2011; 39(2):112-3. · 1.04 Impact Factor
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ABSTRACT: No studies to date have compared mouse models of asthma by evaluating airway histopathology.
To compare 2 such models by studying chronic histopathologic changes of the airways using light and electron microscopy.
Twenty-one male BALB/c mice were divided into 3 groups: a nebulization group sensitized via an intraperitoneal injection of 10 microg ovalbumin on days 0 and 14 and exposed to 2.5% aerosolized ovalbumin 3 days a week over the subsequent 8 weeks; an intranasal group sensitized via 2 intraperitoneal injections of 100 microg ovalbumin on days 0 and 14 and administered an intranasal dose of 500 microg ovalbumin on days 14, 27, 28, 29, 47, 61, 73, 74, and 75; and a control group that received nothing. Airway histopathologies were evaluated.
Basement membrane, epithelium, and subepithelial smooth muscle layer thicknesses and mast and goblet cell numbers were significantly higher in the nebulization group than in the control group. With the exception of mast cell numbers, these parameters were also significantly higher in the intranasal group than in the control group. On comparing the intranasal and the nebulization group, goblet cell numbers were significantly higher in the former and mast cells in the latter.
Both models replicated all the structural parameters of asthma except for mast cell numbers in the intranasal group (no significant difference with respect to the control group). Our findings do not provide sufficient evidence that one protocol is superior to the other. Larger studies are needed to compare different asthma protocols.
Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 02/2009; 19(2):132-8. · 2.27 Impact Factor
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ABSTRACT: Platelet-activating factor (PAF) is an inflammatory mediator involved in the pathophysiology of asthma, suggesting a therapy antagonizing its effects may play a role in the disease treatment. The aim of the study was to determine the effects of Ginkgo biloba, a PAF antagonist, on lung histology. Thirty-five BALB/c mice were divided into five groups; A, B, C, D, and the control. All mice except controls were sensitized and challenged with ovalbumin. Mice in group A (placebo) received saline; group B received G. biloba, 100 mg/kg; group C received G. biloba, 150 mg/kg; and group D received dexamethasone, 1 mg/kg via orogastric gavage for 7 consecutive days. Chronic structural changes and airway remodeling were evaluated by using light and electron microscopy in all groups. Evaluation of lung histology indicated that the number of goblet cells, mast cells, thicknesses of epithelium, and basement membrane were significantly improved in groups B and C when compared with group A. There was no statistically significant difference in thicknesses of subepithelial smooth muscle between groups A, B, and C. When doses of G. biloba were compared with each other, only the number of goblet cells was significantly lower in group C than in group B. When G. biloba and dexamethasone groups were compared with each other, thicknesses of basement membrane and subepithelial smooth muscle were found to be lower in group D than in groups B and C. G. biloba alleviates all established chronic histological changes of lung except smooth muscle thickness in a mouse model of asthma.
Allergy and Asthma Proceedings 01/2009; 30(2):186-91. · 2.17 Impact Factor
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ABSTRACT: Human Echinococcus infection still remains an important health problem in endemic regions. Herein, we report a 5-year-old boy with hydatid disease who has spleen, lung, kidney and liver involvement simultaneously. To our knowledge, there is no pediatric case with hydatid disease in the literature reporting simultaneous involvement of spleen, kidney, liver and lungs as in our case.
Journal of Tropical Pediatrics 08/2008; 54(6):417-9. · 1.39 Impact Factor
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ABSTRACT: Currently, asthma therapies are effective in reducing inflammation but airway remodeling is poorly responsive to these agents. New therapeutic options that have fewer side effects and reverse chronic changes in the lungs are essential. This study aimed to determine the efficacy of oral administration of ginseng on lung histopathology in a murine model of chronic asthma. BALB/c mice were divided into four groups: control, placebo, ginseng, and dexamethasone. All mice except those in the control group were sensitized and challenged with ovalbumin. Then, mice in the ginseng group were given 2 gr/kg per day of ginseng and mice in the dexamethasone group received 1 mg/kg per day of dexamethasone via orogastic gavage once daily for 1 week. Lung histopathology was evaluated by using light and electron microscopy in all groups. All of the chronic changes of airways in the ginseng group were significantly ameliorated when compared with the placebo group. When compared with the dexamethasone group, the ginseng group had significantly lower numbers of mast cell count. Thicknesses of basement membrane, epithelium, and subepithelial smooth muscle were not statistically different between the ginseng and dexamethasone groups. Goblet cell numbers were much more reduced in the dexamethasone group. Ginseng is effective in resolving the established chronic histopathological changes of the lungs in the murine model of asthma.
Allergy and Asthma Proceedings 08/2008; 29(5):493-8. · 2.17 Impact Factor
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ABSTRACT: Brachial artery endothelial dysfunction was shown previously in a small group of Behçet's disease (BD) patients. This study aimed to compare the endothelial function in BD patients with and without vascular involvement. The study group consisted of 25 BD patients with vascular involvement, 25 BD patients without any vascular disease and 46 healthy controls. Brachial artery flow-mediated (endothelium-dependent) dilation (FMD), nitroglycerine-induced dilation and carotid artery intima-media thickness were measured. FMD was impaired in patients with BD (10.41 +/- 3.85%) compared to healthy controls (14.41 +/- 3.39%, p < 0.001). FMD was significantly lower in BD patients with vascular involvement (8.80 +/- 3.63%) than those without any vascular disease (12.02 +/- 3.43%, p = 0.003). This study reveals that endothelial dysfunction documented by brachial artery FMD is a feature of BD, and it is more prominent in patients with vascular involvement.
International Journal of Clinical Practice 08/2005; 59(7):777-81. · 2.41 Impact Factor
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ABSTRACT: This article compares Dempster Shafer's evidence methods' and fuzzy union operators' accuracy and speed criteria for real-time map building process. For real-time applications, it's very important to choose the right operator which can give good results rapidly for different kind of environments. In this study, several fuzzy union techniques are used to integrate sonar measurements for the map representation. The advantage of the method over Dampster-Sheafer approach is discussed. Experimental studies are taken on Nomad 200 robots simulation environment.
Industrial Technology, 2004. IEEE ICIT '04. 2004 IEEE International Conference on; 01/2005
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ABSTRACT: The objective was to investigate the frequency and characteristics of tuberculosis (TB) in patients with systemic lupus erythematosus (SLE). We reviewed the charts of 556 patients with SLE who were followed up between 1978 and 2001 in our lupus clinic. Patients who developed TB after the diagnosis of SLE were identified (SLE/TB+). Ninety-six consecutive patients with SLE who did not develop TB during the follow-up were evaluated as a control group (SLE/TB-). Clinical, laboratory and management characteristics of these two groups of patients were recorded according to a predefined protocol, and compared. Of the 556 patients evaluated, 20 patients (3.6%) with TB were identified. Nine of the 20 patients (45%) had extrapulmonary TB (vertebral involvement in three patients, meningeal in two, and joint and soft tissue in four). Arthritis and renal involvement were significantly high in the SLE/TB+ group (P = 0.045, P = 0.009, respectively). The mean daily dose of prednisolone before the diagnosis of TB and the cumulative dose of prednisolone were significantly higher in the SLE/TB+ group compared to the SLE/TB- group (27 +/- 22 g versus 16 +/- 16 g, 24 +/- 45 mg versus 11 +/- 8.5 mg, respectively). In conclusion, we found an increased frequency of TB infection and a high prevalence of extrapulmonary TB in a large cohort of SLE patients. The mean daily dose of prednisolone before the diagnosis of TB and the cumulative dose of prednisolone, which possibly related to disease severity, were important determinants for the increased risk of TB in these patients with SLE.
Lupus 02/2004; 13(4):274-8. · 2.34 Impact Factor
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ABSTRACT: Leukotrienes, one of the mediators of inflammation in asthma, have a strong bronchoconstrictive effect. L-carnitine has been reported to influence respiratory functions. It has also been reported that L-carnitine inhibits leukotriene synthesis. To evaluate the effects of L-carnitine on oxygen saturation, urine leukotriene E4 levels and lung histopathology in a murine model of asthma, high IgE responder BALB/c mice (n = 24) were systemically sensitized to ovalbumin and chronically challenged with low particle mass concentrations of aerosolized ovalbumin, and then they were divided into 3 groups (study groups A, B, and C) each including eight mice. After methacholine-induced bronchoconstriction, the mice in groups A and B were given intraperitoneal L-carnitine (250 and 125 mg/kg, respectively), while the mice in group C were given placebo. Oxygen saturation of the mice was measured by pulse oxymeter before and after methacholine and after L-carnitine/ placebo application. In addition, urine leukotriene E4 levels were measured before asthma development, and 24-h after L-carnitine injection in asthmatic mice. Inflammation in the lung tissues of the sacrificed animals was scored histopathologically to determine the effect of L-carnitine on tissue level. A control group of non-sensitized mice (n = 8) treated with placebo only was used for comparison of urine leukotriene E4 levels and of histopathological parameters. Oxygen saturation of the mice in the study groups tended to decrease after methacholine and to improve after L-carnitine injection, although these changes were not significant at all time points. Urine leukotriene E4 levels of all 3 study groups increased significantly after asthma development. The rate of increment was smallest in the group given the highest L-carnitine dose (group A). Inflammation at the tissue level was also mildest in group A, and severest in the group that was not given carnitine (group C). All of the study groups and the control group differed significantly with respect to inflammation scores. In conclusion, L-carnitine improved oxygen saturation, and decreased urine leukotriene E4 levels and inflammation in lung tissues in the present murine model of asthma.
Acta Medica Okayama. 01/2002;
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Pediatrics International 09/2001; 43(4):420-2. · 0.63 Impact Factor
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ABSTRACT: Some lifestyle factors may be important for the occurrence of wheezing and there are considerable differences around the world.
Risk factors of wheezing were examined in 38 children (aged 6-24 months). Results were compared with healthy age-matched controls.
Family history of atopy, asthma and eczematoid dermatitis, and parental and pregnancy smoking were all reported as being substantially more common in wheezing infants than in controls (P < 0.05 for each parameter). Living conditions showed that the incidence of wheezing in infants was more common in households with wooden floor coverings compared with controls, which used plastic floor coverings (P < 0.05). They also showed that 55.3% of wheezing infants and only 20% of controls were living in moist dwelling environments (P < 0.05). With regard to bedding, the incidence of wheezing in infants was higher in households using synthetic materials compared with controls (P < 0.05). A history of in utero and environmental tobacco smoke exposure was associated with increased risk of recurrent wheezing. Odds ratio and logistic regression analysis were done with presence of wheezing as the dependent variable and all risk factors of interest as independent variables. Family history of atopy, high household humidity levels, parental smoking and wooden floors used in the home were significant risk factors for wheezing. Skin test positivity and gastroesophageal reflux were determined in wheezing infants as 18.4 and 13.2%, respectively.
Recurrent wheezing in infancy may be associated with many environmental and genetic factors. It is possible that allergen avoidance merely delays rather than prevents the development of allergic disorders.
Pediatrics International 05/1999; 41(2):147-50. · 0.63 Impact Factor
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ABSTRACT: Gastroesophageal reflux (GER) is implicated in the pathogenesis of respiratory symptoms in childhood. It should be taken into account especially in the differential diagnosis of children presenting with wheezing. Although, oesophageal pH monitorization has been reported to be the best technique in the evaluation of GER, radionuclide studies have also been shown to be very sensitive recently. In this study, 82 children presenting with recurrent wheezing (n = 74) and/or vomiting (n = 28) (mean age 17.4 months; range 3-48 months) were evaluated. GER scintigraphy was performed to determine the frequency of GER. GER was determined in 18 of the 82 cases (21.9%). The GER was found in 21.1% of children with recurrent wheezing and in 16.6% of children suffering from recurrent vomiting. GER scintigraphy should be kept in mind in the evaluation of children with the complaint of recurrent wheezing since it is a noninvasive and easily applicable method.
The Indian Journal of Pediatrics 04/1999; 66(3):351-5. · 0.52 Impact Factor
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ABSTRACT: The wheezing infant is a common but difficult patient to approach diagnostically. The prevalence of immunoglobulin (Ig) G subclass deficiency in wheezing infants is still controversial.
We studied the serum concentration of IgG subclasses in 38 wheezing infants (aged 6-24 months) who had not received systemic steroids before investigation and in 30 healthy age matched controls (aged 6-24 months).
The prevalence of one or more IgG subclass deficiencies was 31.6% in wheezing infants and 26.7% in controls. There was no significant difference in prevalence of IgG subclass deficiency between patients and controls (P > 0.05). The mean concentration of IgG subclasses in patients were compared with controls. There was no significant difference in mean serum concentration of IgG1, G2 and G3 subclasses. However, there was a trend towards higher concentrations of IgG4 in wheezing infants and this difference for IgG4 was significant (P < 0.01). Immunoglobulin G subclass deficiency was found in 25 and 36.4% of wheezing infants who had experienced from two to four and five or more wheezing episodes in 2 years, respectively (P > 0.05).
Our findings suggest that wheezing in infancy is not associated with IgG subclass deficiency, and in wheezing infants low IgG subclasses levels do not increase the frequency of wheezing. However, there is a relationship between recurrent wheezing and serum IgG4 subclass concentration.
Acta paediatrica Japonica; Overseas edition 01/1999; 40(6):564-6.
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Allergy 07/1997; 52(6):689-90. · 6.27 Impact Factor
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ABSTRACT: Adolescence is a period which is characterized by rapid physical growth and development of secondary sex characteristics. Male adolescence begins at 11-12 years of age and lasts approximately 5 years. During this interval, there is a growth spurt period which is observed any time between 11 and 16 years of age, lasting 2-3 years. Some authors claim that a male may have nearly 20-25% of his adult height and 50% of his adult weight during adolescence. When evaluating the maturational aspects of adolescence, it is essential to consider bone age (BA) as well as chronological age (CA). Bone age is the mean CA at which the skeletal maturation is normally attained. It is influenced by genetic, endocrinological and nutritional factors. An adolescent may not demonstrate the expected maturational steps if his BA is retarded. This report examines the relationship between CA, biological maturation and some anthropometrical measurements.
Acta paediatrica Japonica; Overseas edition 03/1994; 36(1):84-7.
