Mukadder Çalikoğlu

Glutathione-S-transferase gene polymorphisms (GSTT1, GSTM1, GSTP1) as increased risk factors for asthma.

Objectives:  Asthma is a complex multifactorial disease with an obvious genetic predisposition, immunological aberration, and involvement of noxious environmental factors. Polymorphisms of the glutathione‐S‐transferase (GST) genes are known risk factors for some environmentally‐related diseases. In the present study, the hypothesis that polymorphisms in the GSTT1, GSTM1 and GSTP1 genes are associated with atopic and nonatopic asthma was examined.

Leptin and TNF-Alpha Levels in Patients with Chronic Obstructive Pulmonary Disease and Their Relationship to Nutritional Parameters

Background: Leptin is a protein mainly secreted by adipocytes, and the major function of leptin was its role in body weight regulation. In humans, there was a strong correlation between leptin and nutritional parameters, such as body mass index (BMI) and fat mass (FM). Administration of recombinant leptin to ob/ob mice, which have a genetic defect in leptin production, reduces food intake, increases energy expenditure, and decreases body weight. It is suggested that increased levels of circulating leptin levels may contribute to anorexia and weight loss in pathologic conditions including chronic obstructive pulmonary disease (COPD). Recent studies have provided evidence for a link between leptin and proinflammatory cytokines such as TNF-α. Objective: This study aimed to detect serum leptin and TNF-α levels in COPD patients without weight loss during stable disease and acute exacerbation, and to investigate relationships between leptin, TNF-α and nutritional parameters at different stages of the disease. Material and Methods: 26 stable COPD patients, 16 COPD patients with acute exacerbation and 15 control subjects participated in this study. To eliminate the effects of sex differences, all patients and controls were male. BMI, percent ideal body weight, percent FM, sum of skinfold tickness and serum leptin and TNF-α levels were measured in all participants. Leptin and TNF-α levels were measured by ELISA. Results: Serum leptin and TNF-α levels were significantly higher in the patients experiencing exacerbation than in the stable patients and controls. Although leptin levels were lower and TNF-α levels were higher in the stable patient group than in the controls, these differences were not statistically different. Leptin levels were significantly correlated with the nutritional parameters in both control and stable groups. However, in patients with acute exacerbation, a correlation between leptin and nutritional parameters was not found. There was no significant relationship between TNF-α and nutritional parameters in the three groups. In addition, while there was no correlation between leptin and TNF-α levels in the stable and control groups, a significant positive correlation was observed in patients with exacerbation. Conclusion: In conclusion (1) elevated TNF-α levels may be related to increased inflammation in patients, (2) circulating TNF-α levels were associated with increased leptin levels and (3) although leptin and nutritional parameters were correlated in the stable COPD patients, the correlation was weaker compared to controls, and during an exacerbation it disappeared completely. Therefore, inappropriately increased levels of leptin and TNF-α noted during recurrent acute exacerbations in patients with COPD may lead to changes in nutritional parameters and body weight in the course of the disease.

The effects of caffeic acid phenethyl ester on tissue damage in lung after hindlimb ischemia-reperfusion

AIM The aim of this study was to investigate the effects of caffeic acid phenethyl ester (CAPE) on the lungs as a remote organ after performing hindlimb ischemia-reperfusion (I/R) and by assessing biochemical and histopathological analysis. METHODS The animals were divided into three groups: control, I/R, and I/R with CAPE. I/R period for 8 h was performed on the right hindlimb of all the anesthesied rats in I/R and CAPE with I/R group. In the CAPE with I/R group, the animals received CAPE 10 microM by intraperitoneal injection 1h before the reperfusion. The animals in the control and I/R groups received a similar volume of saline solution by means of intraperitoneal injection. At the end of the reperfusion period, a midsternotomy was performed. Blood, bronchoalveolar lavage (BAL) and lung tissue were obtained, and were used for biochemical and histopathological examination. RESULTS The tissue and serum malondyaldehyde levels were significantly lower in the control (P=0.0001 and 0.001, respectively) and in the CAPE with I/R groups (P=0.0001 and 0.003, respectively) compared to the I/R group. Tissue Na(+)-K(+) ATPase activity in the CAPE with I/R group was significantly higher than in the I/R group (P=0.0001). Reduced activity was found in the I/R group compared to the control group (P=0.0001). Myeloperoxidase activity (P=0.001) and protein concentration (P=0.034) in BAL were significantly reduced in CAPE-treated animals when compared with the I/R group. A decreased activity and protein concentration were found in the control group compared to the I/R group (P=0.0001 and 0.024, respectively). The lungs of the I/R group displayed intense peribronchial and perivascular leukocytic infiltration in histopathological examination compared to the CAPE with I/R group (P<0.05). CONCLUSION CAPE seems to be effective in protecting remote organ injury caused by increased oxidative stress and neutrophil accumulation that results from an I/R injury.

The levels of serum vitamin C, malonyldialdehyde and erythrocyte reduced glutathione in chronic obstructive pulmonary disease and in healthy smokers

Abstract There is an increasing interest in the concept that oxidant/antioxidant imbalance plays a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, most of the studies are concentrated on the local antioxidant/oxidant balance. In this study, we investigated the oxidant/antioxidant balance in systemic circulation of patients with COPD. Serum malonyldialdehyde (MDA), vitamin C and erythrocyte reduced glutathione (GSH) were determined in patients during acute exacerbation and during the stable phase of the disease, and compared with age-and sex-matched healthy controls. The levels of serum MDA, vitamin C and erythrocyte GSH were determined according to Yagi, Beutler and Bauer et al., respectively. Serum MDA levels were significantly higher in patients compared to controls, and during acute exacerbation compared to the stable phase. MDA levels in patients with acute exacerbation and in those in stable phase were also higher than in controls. We found significantly decreased levels of erythrocyte GSH and serum vitamin C in patients with acute exacerbation and stable COPD compared to controls. Although smoking caused an increase in oxidative stress in controls, the measured parameters were not affected by smoking in the patient group. In conclusion, there is a systemic oxidant/antioxidant imbalance in COPD, and this imbalance is probably independent of smoking.

Respiratory symptoms and pulmonary functional changes in patients with irritable bowel syndrome

OBJECTIVE:Scientific evidence of functional interface between the immune and sensory motor systems of the gut and respiratory systems has been reported. In recent studies excess prevalence of bronchial hyper-responsiveness has been shown among patients with irritable bowel syndrome (IBS). The purpose of our study was to investigate the possible relationship between IBS and asthma.METHODS:One hundred thirty-three patients with IBS (108 women, 25 men) and 137 control subjects (105 women, 32 men) were included in this study. Both for IBS and the control group, the mean ages were 41.64 ± 9.45 yr and 39.94 ± 10.62 yr, respectively. Patients more than 50 yr old, with any organic GI disease, acute respiratory system infection, current or ex-smokers, and patients using drugs affecting smooth muscle and autonomic nervous system were not included in the study. Respiratory symptoms were questioned and pulmonary function tests were performed for every subject.RESULTS:There were 45 (33.8%) and eight (5.8%) subjects with respiratory symptoms in IBS and control groups, respectively (p < 0.0001). Twenty-one (15.8%) patients from the IBS group and two (1.45%) patients from the control group had the diagnosis of asthma according to history, clinical, and PFT findings. There was no statistical difference between two groups with respect to percentage of forced vital capacity and forced expiratory volume in 1 s-to-forced vital capacity. The difference between the two groups in forced expiratory volume in 1 s, flow after 50% of the vital capacity has been exhaled, peak expiratory flow rate, and maximal mid-expiratory flow rate was statistically significant (p < 0.01).Conclusion:We found that the prevalence of asthma was more common in the IBS group than in controls. Our finding supports the speculation that asthma and IBS may share common pathophysiological processes

Respiratory muscle strength but not BASFI score relates to diminished chest expansion in ankylosing spondylitis

Pulmonary function is altered in ankylosing spondylitis (AS) owing mainly to the restriction of chest wall involvement (limited chest expansion). The objective of this study was to investigate the relationship between chest expansion, respiratory muscle strength (MIP, MEP) maximum voluntary ventilation (MVV), and BASFI score in patients with AS. Twenty-three male patients with definite AS and 21 age-matched healthy male controls were recruited for the study. Patients with AS were assessed for functional status by BASFI. Measurement of chest expansion and lumbar spinal flexion (modified Schober) method was performed in all subjects. Pulmonary function tests were performed by spirometry. Respiratory muscle strength was evaluated by a mouth-pressure meter (MPM). Body mass index (kg/m2) was recorded in all individuals. Chest expansion and modified Schober measurement were significantly lower in AS patients (p<0.05). Pulmonary function tests revealed restrictive lung disease. The mean BASFI score suggested good functional capacity in the AS group. The respiratory muscle strength and MVV were also lower in AS (p<0.05). The chest expansion was correlated with MIP and MEP values (r=0.491; p=0.02, r=0.436; p=0.05). Chest expansion was also correlated negatively with disease duration (r=−0.502; p=0.03). In addition, there was no correlation between chest expansion and BASFI score (r=−0.076; p=0.773). This study demonstrates that functional status (BASFI) is not influenced by the limitation of chest wall movement. It may be as a result of the maintenance of moderate physical activity during active life in patients with AS.

The Association Between Polymorphic Genotypes of Glutathione S-Transferases and COPD in the Turkish Population

Although smoking is regarded as the most important causal factor in chronic obstructive pulmonary disease (COPD), only 10–20% of smokers develop symptomatic COPD, which indicates the presence of genetic predisposing factors in its pathogenesis. This study investigates the association between gene polymorphysims of glutathione S-transferases (GSTs) and COPD. Blood samples were taken from 149 patients and 150 healthy controls. Polymorphisms of GSTT1, GSTM1, and GSTP1 were genotyped using Real-Time PCR. Multivariate logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals between specific genotypes and COPD. There was no difference in the frequencies of the genotypes of GSTM1 and GSTT1 between the groups, but the GSTP1 Ile/Ile genotype was significantly higher in the patients than in the controls (61.1% vs. 38%). GSTP1 Ile/Val and Val/Val genotypes were associated with a decreased risk of COPD when compared to the Ile/Ile genotype (2.12-fold and 4-fold, respectively). Thus we suggest that the Val allele of GSTP1 may have a protective effect for development of COPD. Furthermore, when we evaluated the association between GSTP1 genes and smoking status, smokers with the GSTP1 Ile allele had an increased risk for the development of COPD. Among the combinations of the genotypes, the combination of GSTM1, GSTT1 null, and GSTP1 Val/Val was associated with the maximal increased risk (12-fold) of COPD. Thus to explain the ethiopathogenesis of COPD, investigation of a single gene family is inadequate. Based on our results and the previous data, further studies should be focused on the GSTP1 gene and the interactions with other genes such as polymorphisms of N-acetyltransferases, GSTM1 and GSTT1, microsomal epoxide hydrolase, and allelic variants of cytochrome P450.

Alcohol-induced lung damage and increased oxidative stress.

Background: Alcohol-induced lung damage may be associated with increased oxidative stress. Objective: Our aim was to investigate alcohol-induced changes in the biochemistry and histopathology of the lung. Methods: Rats were divided into two groups, a control group and an ethanol group. The ethanol group received 2 g/kg ethanol (total: 3 ml) intraperitoneally. The controls were given the same amount of saline via the same route. Three hours later, the rats were sacrificed, and blood and lung tissue samples were obtained. Oxidative stress was assessed by measuring the levels of erythrocyte reduced glutathione (GSH), tissue malondialdehyde (MDA), myeloperoxidase (MPO) and Na+-K+ ATPase. Histopathologic evaluation of the lung tissues was also performed. Results: In the ethanol group, serum and tissue MDA levels and MPO activities were increased (p = 0.007, p = 0.001 and p = 0.000), and lung tissue Na+-K+ ATPase activities and erythrocyte GSH were decreased (p = 0.001 and p = 0.000) compared to the controls. Histopathologic examination demonstrated alveolocapillary thickening, alveolar degeneration, leukocyte infiltration and erythrocyte extravasation in the lungs of the ethanol group (p < 0.05). Conclusion: These results suggest that high-doseacute alcohol administration aggravates systemic and local oxidative stress leading to acute lung injury, ranging from mild pulmonary dysfunction to severe lung injury. It should be borne in mind that rapid onset of the acute respiratory distress syndrome (ARDS) may also be due to increased oxidative stress following alcohol abuse, especially when ischemic disturbances, e.g. coronary heart disease, acute ischemia of the extremities and traumatic accidents, are concomitantly present. Therefore, precautions against ARDS may prevent morbidity and mortality in alcohol-induced lung damage in at-risk patients.

HRCT evaluation of the accessory fissures of the lung

INTRODUCTION The purpose of this study was to classify the accessory fissures of the lung and to assess their frequency by using high-resolution CT. METHODS AND PATIENTS HRCT scans of 115 patients were prospectively reviewed. 1 mm thin sections were obtained at 10 mm intervals with a scan time of 1.9 s. The fissure and its relationship to the segmental bronchovascular structures were then evaluated on transverse sections. RESULTS Forty-four accessory fissures were detected in 35 of 115 patients. The most common accessory fissure was the inferior accessory fissure (12%). The second most common accessory fissure was the left minor fissure (8%). The right superior accessory fissure (5%), the accessory fissure between the medial and lateral segments of the right middle lobe (5%), and the accessory fissure between the superior and inferior segments of the lingula (5%) were seen in equal frequencies. Also, intersegmental accessory fissures, namely the fissure between the anterobasal and laterobasal of both the right (1%) and the left (2%) lower lobes were detected. We found only one subsegmental accessory fissure. DISCUSSION AND CONCLUSION The inferior accessory fissure and the left minor fissure were the most common accessory fissures in our study.

Pulmonary function tests, respiratory muscle strength, and endurance of patients with osteoporosis

Background It has been shown that patients with thoracic kyphosis due to osteoporosis have diminished pulmonary function. The aim of this study was to determine the pulmonary function, respiratory muscle strength, and endurance of patients with osteoporosis who did not have compression fractures. Methods The patient group consisted of 88 recently diagnosed postmenopausal osteoporotic women without spinal fractures. They were matched for age and body mass index with 54 healthy women, who formed the control group. Bone mineral density, pulmonary function test (PFT), maximum voluntary ventilation (MVV), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) measurements of both groups were performed. Results There were no significant differences between the two groups regarding PFT parameters and MIP and MEP. However, osteoporotic patients had significantly lower MVV values. Conclusion Women with postmenopausal osteoporosis without spinal compression fractures have normal PFT, MIP, and MEP values, but they have reduced respiratory muscle endurance.