The association between BsmI variant of vitamin D receptor gene and susceptibility to tuberculosis.

Vitamin D receptor (VDR) gene variants may play a key role in the susceptibility to tuberculosis (TB). We have investigated the association BsmI, TaqI, FokI polymorphisms in the VDR gene with susceptibility to tuberculosis. This study included 128 patients with TB (pulmonary and extrapulmonary TB) and 80 healthy subjects living in Istanbul, Turkey. Genetic polymorphisms were studied by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques at genomic DNA isolated from whole blood-EDTA. The present study results indicate that the genotype and allele frequencies for patient group (BB:22, Bb:53, bb:25; B allele:48%, b allele:52%) was significantly different from the control group (BB:6, Bb:48, bb: 46; B allele:30 b allele:70) due to an overrepresentation of B allele (P: 0.000 OR: 1.61 95% 1.23-2.11). However there were no significant differences in distribution of allele/genotype frequencies of FokI, TaqI variants between TB and healthy controls. This study results suggest that BsmI variant of VDR gene may play an important role in susceptibility to tuberculosis.

Analysis of transforming growth factor beta 1 (TGF-beta1) gene polymorphisms in Turkish patients with scleroderma.

Systemic sclerosis (SSc) is an autoimmune disease characterized by inflammation and fibrosis of the skin and visceral organs. Fibrosis associated with SSc is characterized by an increased synthesis of a wide range of extracellular matrix (ECM). TGF-beta is a pluripotent cytokine in a wide range of cell types. In particular it has been found to be a potent inducer of ECM protein synthesis and fibroblast migration. The TGF-beta1 gene is highly polymorphic and two signal sequence polymorphisms at codon 10 and codon 25 are linked to disease outcomes. In this study, we analysed two polymorphic sites of the TGF-beta1 gene, codon 10 and codon 25, in 43 Turkish SSc female patients with interstitial lung involvement and in 75 healty individuals by ARMS-PCR. In our study no significant difference was found in codon 10, codon 25 genotype frequencies between patient with SSc and the control group (p = 0.676, 0.375, respectively). Our findings suggest that codon 10 and 25 polymorphism cannot be related with SSc for Turkish population.

Epidemiological features of Turkish patients with sarcoidosis.

Epidemiological characteristics of sarcoidosis differ according to geographical distribution. The aim of our study was to disclose epidemiological characteristics in our country. The data was collected from investigators, who sent information on newly-diagnosed patients via internet. In 2 years 198 female and 95 male patients were enrolled to the study (f/m:2.08). Mean age of patients was 44+/-13 years (17-90). Mean age of male patients was 38+/-12 while mean age of female patients was 48+/-13 (p<0.001). 73.4% of patients were nonsmokers (85.4% of females; 48.4% of males; (p<0.001)). About 50% of our 293 patients were housewives. Familial sarcoidosis was found in 3 patients' first degree relatives. Estimated annual incidence of sarcoidosis for Turkey was calculated as 4 per 100,000 person. According to our study, 2/3 of sarcoidosis patients were women; mean age of patients was 45 and the disease began 10 years later in female patients. 80% of patients were nonsmokers; negative relation between sarcoidosis and smoking was evident especially in women. Familial sarcoidosis frequency was lower compared to other studies in the literature. There was no occupational exposure history in our patients. Our incidence rate, is similar with the results of other European studies.

NRAMP1 (SLC11A1) gene polymorphisms that correlate with autoimmune versus infectious disease susceptibility in tuberculosis and rheumatoid arthritis.

NRAMP1 gene has multiple pleiotropic effects on macrophage activation pathways. These pleiotropic effects may increase resistance to infections such as tuberculosis (TB), but may also lead to susceptibility of autoimmune diseases such as rheumatoid arthritis (RA). It has been hypothesized that allele 3 would be associated with autoimmune diseases, whereas allele 2 would be associated with infectious diseases, and genetic factors that enhanced survival in the epidemics of TB might have led to susceptibility for the development of RA. We analysed four NRAMP1 gene polymorphisms including 5' promoter (GT)(n) (rs34448891), INT4 (469 + 14G/C) (rs3731865), 3'UTR (1729 + 55del4) (rs17235416) and D543N (codon 543, Asp to Asn) (rs17235409) in 112 patients with TB, 98 patients with RA, 80 healthy controls for TB and 122 healthy controls for RA using ARMS-PCR and PCR-RFLP. We found a significant association between INT4 and RA (P = 0.004, odds ratio: 2.06, 95% CI: 1.24-3.41), but no significant differences between 5' promoter, D543N, 3'UTR polymorphisms and RA. There were no associations between NRAMP1 gene polymorphisms and TB. Similarly, no significant differences were observed between NRAMP1 polymorphisms and rheumatoid factor positivity and erosive disease in RA and localization of TB. INT4 polymorphism may be associated with RA in Turkish patients.

Association between 'interleukin' 10 gene (IL10) polymorphisms and systemic sclerosis with interstitial lung involvement.

Systemic sclerosis (SSc), also termed as "scleroderma", is a progressive, systemic disease of unknown origin characterized by excessive fibrosis, vascular abnormalities and immune dysfunction. Extracellular matrix (ECM) production by fibroblasts in SSc is modulated and regulated by cytokines. Since IL10 has antiinflamatory properties and, contributes to the fibrotic processes in SSc, we analyzed IL-10 gene polymorphisms including -1082 G/A, -819 C/T and -592C/A in 45 systemic sclerosis patients with lung involvement and 150 healthy control using ARMS-PCR. While no association was found between SSc and -819C/T, -592C/A polymorphism, -1082 G/A allele frequency in SSc patients was higher than that in control and significant association was found between SSc and -1082 G/A (Pc: <0.000, OR: 2.85 95% CI: 1.74-4.63). In addition significant difference was found between the frequencies of the IL-10 GCC, ACC haplotypes (Pc: <0.000, OR: 2.85, 95% CI: 1.74-4.63; Pc: 0.012, O.R: 1.56, 95% CI: 1.09-2.23, respectively), GCC(+)/GCC(+), GCC(-)/GCC(-) genotypes (Pc: 0.002, OR: 5.07, 95% CI: 1.82-14.21; Pc: <0.000, O.R: 4.00, 95% CI: 1.87-8.98, respectively) and SSc. Our findings suggest that IL-10 1082 G/A alleles or haplotypes containing these alleles may play role in SSc susceptibility.

Interleukin-10 and tumor necrosis factor-alpha gene polymorphisms in tuberculosis.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is an infectious disease in humans killing nearly three million people and eight million cases annually. The cytokines TNF-alpha and IL-10 have been implicated in the pathogenesis of TB. Certain single nucleotide polymorphisms within the promoter region of the IL10 and TNF genes have been associated with altered levels of circulating IL10 and TNF-alpha. We analyzed TNF-alpha (-308 G/A, -238 G/A, -376 G/A) and IL10 (-1,082 G/A, -819 C/T, -592 C/A) polymorphisms in 128 patients with TB and 80 healthy subjects using by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). A significant association was found between TB and -1,082 G allele (Pc: 0.000, O.R 2.22, 95% CI 1.45-3.41). Significant difference was observed in IL10 GCC and ACC haplotypes distribution between TB and control subjects (Pc: 0.000, O.R 2.22, 95% CI 1.45-3.41; Pc: 0.004, O.R 0.53, 95% CI 0.35-0.81). No statistically significant association was found between IL-10 -819 C/T, TNF-alpha 308 G/A, -238 G/A, -376 G/A polymorphisms, functional TNFalpha/IL-10 genotypes and TB. Our findings suggest that IL-10 1082 G/A alleles or haplotypes containing these alleles may influence the Th1/Th2 balance and hence may play a role in TB susceptibility and increase risk of developing disease. This polymorphism may be one of the many genetic factors affecting disease outcome.

NRAMP1 (SLC11A1): a plausible candidate gene for systemic sclerosis (SSc) with interstitial lung involvement.

Systemic sclerosis (SSc), also termed "scleroderma," is a progressive, systemic disease of unknown origin characterized by excessive fibrosis, vascular abnormalities and immune dysfunction. Nramp 1 gene has multiple pleiotropic effects on macrophage activation pathways, including up-regulation of the chemokine/cytokine genes KC, tumor necrosis factor alpha, interleukin-1 b, inducible nitric oxide syntase, and major histocompatibility complex class II expression, as well as tumoricial activity and antimicrobial activity. All of these pleiotropic effects are important for resistance to infection, but they may also be involved in the induction and maintenance of autoimmune diseases. We analyzed four natural resistance associated macrophage protein 1 (NRAMP1) gene polymorphisms including 5' promoter (GT)n microsatellite, INT4 (469 + 14G/C), 3'UTR (1729 + 55del4), and D543N (codon 543, Asp to Asn) in 52 systemic sclerosis patients with interstitial lung involvement and 136 healthy controls. We found a significant association between INT4, (GT)n polymorphisms (p = 0.006 and 0.027, respectively), and SSc. Our findings suggest that NRAMP1 is a plausible candidate gene for SSc.

Attenuation of acute lung injury following lower limb ischemia/reperfusion: the pharmacological approach.

AIM: The purpose of this study was to examine the effects of N-acetylcysteine (NAC), calcium dobesilate (DOBE) and aprotinin on the amelioration of lung damage following ischemia/reperfusion injury in a rat hind limb model. A well known antioxidant dimethyl-sulfoxide (DMSO) was also tested for comparison. METHODS: Ischemia was induced in the lower limb for 4 h by vascular clamping and followed by 1 h of reperfusion. Lung injury was evaluated in 5 groups as a saline (control), DMSO, NAC, DOBE and aprotinin group. Plasma creatine kinase, lactate dehydrogenase, thiobarbituric acid reactive substances (TBARS) as well as lung tissue TBARS levels were measured. Lung tissue samples were taken for histological examination. P<0.005 was considered statistically significant. RESULTS: Plasma TBARS values were found to be significantly lower in the DMSO (P<0.005), NAC (P<0.005) and aprotinin (P<0.005) groups compared to the control group. Lung TBARS values were significantly lower in the DMSO, NAC, DOBE and aprotinin groups compared to the control group (P<0.001, P<0.001, P<0.001). Also in the aprotinin group lung TBARS values were found to be significantly lower compared to DMSO (P<0.001), NAC (P<0.001) and DOBE (P<0.001) groups. Histological examination showed less prominent peribronchial leukostasis (P<0.005) and interstitial leukostasis (P<0.005) in all drug groups compared to the control group. CONCLUSION: These observations indicate that DOBE and NAC, which are known to have antioxidant properties and aprotinin, a serine proteinase inhibitor, acted effectively on the prevention of lung injury in a rat hind limb ischemia/reperfusion model. The reason why aprotinin exerts a more protective effect than the other drugs is not clear, however, its clinical use may have the dual advantage of hemostasis and lung protection in surgical practice.

Comparison of extra-pulmonary and pulmonary tuberculosis cases: factors influencing the site of reactivation.

SETTING: Mycobacterium tuberculosis bacilli spread by the hematogenous route during primary infection and reactivate later. OBJECTIVE: To compare factors influencing the reactivation site. DESIGN: A total of 236 pulmonary tuberculosis (PTB) and 139 extra-pulmonary TB (EPTB) cases were compared in terms of age, co-morbid disease, immunosuppressive drug use, history of contact with a PTB case in a close relative, history of tuberculosis, smoking habit and alcohol intake. RESULTS: The sex ratio of EPTB and PTB cases was significantly different (P < 0.001): respectively 74% of EPTB cases and 34% of PTB cases were females; 53.3% of PTB cases and 23% of EPTB cases were smokers (P < 0.001); and the disease appeared within the first 5 years after contact in 23.7% of EPTB cases compared to 72.6% in PTB cases (P < 0.001). In logistic regression analysis, gender (OR = 3.69), smoking habit (OR = 0.54) and interval between contact and disease (OR = 1.07) were found to influence the reactivation site. CONCLUSION: The probability of PTB development was higher in males, in smokers and within the first 5 years of contact. In contrast, the probability of EPTB development was higher in females and after 5 years of contact.

Determination of the etiological organism during acute exacerbations of COPD and efficacy of azithromycin, ampicillin-sulbactam, ciprofloxacin and cefaclor. Turkish Thoracic Society COPD Working Group.

Acute exacerbations, most of which are due to lower respiratory tract infections, cause great morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD) and most of these are due to lower respiratory tract infections. The aim of this study was to determine the causative organism and the effects of azithromycin, ampicillin sulbactam (sultamicillin), ciprofloxacin and cefaclor monohydrate therapy in COPD. One hundred and six patients with COPD in acute exacerbation were randomized into four groups for empiric antibiotic treatment following lung function tests and sputum examination. The most common strains isolated from sputum were Haemophilus influenzae (30.8%), Streptoccocus pneumoniae (12%) and Moraxella catarrhalis (7.7%). Azithromycin, sultamicillin, ciprofloxacin and cefaclor monohydrate were found to be effective in treating COPD exacerbations.