MMP2 -1306C>T polymorphism in patients with COPD

The remodeling of the bronchial walls is an important process of the pathophysiology of COPD as the matrix metalloproteinase-2 (MMP-2) is shown to play an important role in this process. The aim of the current study was to elucidate the possible role of MMP2 -1306C>T promoter polymorphism as risk factor of COPD. We genotyped by PCR-RFLP 84 patients with COPD and 71 control individuals. The genotype, but not allele distribution, differed between COPD patients and controls (p=0.021 and 0.602, respectively). Carriers of the variant T allele (CT+TT) tended to have 1.64-fold higher risk for COPD (95% CI: 0.82-3.26, p=0.164) than those with CC genotype, as that risk was significant in the subset of older than 65 years individuals (OR=4.24, 95% CI:1.31-13.57, p=0.019). The risk for COPD of T carriers (CT+TT) was significant and even higher in the subset of older individuals (more than 65 years) and in those without diabetes as a co-morbidity. Patients with T genotypes had later onset of the disease (64.1±7.1 years) than those with CC genotype (59.7±9.5 years, p=0.045). In conclusion, our results suggest that the T genotypes of MMP2 -1306C>T SNP may determine a risk for COPD especially in advanced age

Effects of common functional MMP12 gene polymorphisms on PD in a Polish population

The present study investigated associations of two functional MMP12 polymorphisms with PD risk and cognitive impairment in PD. A total of 478 study subjects (241 PD and 237 age and sex matched controls) were included in the study. UPDRS score, Hoehn–Yahr staging and Schwab–England scale were used to assess motor abilities and activity during daily life. All patients were classified into groups with dementia (PDD, n=72) and without dementia (nPDD, n=159) based on the neuropsychological assessment. The two most common functional single nucleotide polymorphisms (SNPs) in MMP12 gene were determined using TaqMan real-time PCR assays. Frequencies of evaluated MMP12 rs2276109 alleles and genotypes were similar in PD and the controls, whereas rs652438G allele genotypes were significantly more frequent among healthy individuals (p=0.013, OR 0.47 (0.26–0.85). The rs2276109 and rs652438 allele and genotype frequencies were not associated with dementia in PD patients. The current results suggest that MMP12 rs652438 but not MMP12 rs2276109 may affect the risk for PD, as the minor G allele genotypes might be a protective factor

The leukocyte telomere length, single nucleotide polymorphisms near TERC gene and risk of COPD

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and is associated with chronic local and systemic inflammation and oxidative stress. The enhanced oxidative stress and inflammation have been reported to affect telomere length (TL). Furthermore, a number of SNPs at loci encoding the main components of the telomerase genes, TERT and TERC have been shown to correlate with TL. We aimed to explore the leukocyte TL and genotypes for single nucleotide polymorphisms, rs12696304 (C > G) and rs10936599 (C > T) near TERC in COPD cases and matched healthy controls using q-PCR technologies. Successful assessment of TL was performed for 91 patients and 88 controls. The patients had shorter TL (17919.36 ± 1203.01 bp) compared to controls (21 271.48 ± 1891.36 bp) although not significant (p = 0.137). The TL did not associate with the gender, age, spirometric indexes, smoking habits but tended to correlate negatively with BMI (Rho = − 0.215, p = 0.076) in the controls, but not in COPD patients. The genotype frequencies of the SNPs rs12696304 and rs10936599 were compared between patients and controls and the odds ratios (OR) for developing COPD were calculated. The carriers of the common homozygous (CC) genotypes of the SNPs had higher risk for COPD, compared to carriers of the variants alleles (rs12696304 CG+GG vs. CC; OR: 0.615, 95% CI [0.424–0.894], p = 0.011 and for rs10936599 CT+TT vs. CC OR = 0.668, 95% CI [0.457–0.976], p = 0.044). Analysis on the combined effects of the TERC rs12696304 (C > G) and rs10936599 (C > T) genotypes, CC/CC genotype combination was associated with higher risk for COPD (p < 0.0001) and marginally lower FEV1% pr. in patients with GOLD II (p = 0.052). There was no association between the SNP genotypes and TL. In summary, our results suggest that COPD patients may have shorter TL, and rs12696304 and rs10936599 near TERC may affect the risk of COPD independently of TL

In Vitro Model for Evaluation of Cancer Cell Proliferative Activity under Simulated Acidosis and Using Chitosan Microparticles

This investigation provides experimental data related to the development of a useful in vitro model allowing for a deeper analysis of invasive (metastatic) cancer cells using the effect of forced acidosis on the behavior of an epithelial colon cancer cell line. The results demonstrate that incubation in the medium with different pH values, adjusted by hydrochloric or lactic acids, increased more than 20 fold the proliferative activity of cancer cells at 48 h of incubation without affecting their cell viability. The newly synthesized chitosan micro-formulations were tested as a potential system for the screening of cancer progression, based on the attachment of cancer cells to the chitosan surface, without radically disturbing their viability. The latter could allow us to develop a versatile and useful in vitro model for the detailed investigation of the biological and molecular biochemical processes of invasive (metastatic) cancer cells

Network Management/Social Help Tool

Available under the three clause BSD licence, Copyright TENCompetence Foundation.Prototypes of a tool that should manage ad hoc transient communities, focusing on mutual, peer-to-peer support of learning network users. Usage of ad hoc transient communities should be a generic device to increase the connectivity of members of networked communities.The work on this publication has been sponsored by the TENCompetence Integrated Project that is funded by the European Commission's 6th Framework Programme, priority IST/Technology Enhanced Learning. Contract 027087 [http://www.tencompetence.org

Possible Role of Serum Leptin as Biomarker in COPD

Leptin is one of the adipokines shown to exert a significant effect in respiratory diseases, including chronic obstructive pulmonary disease (COPD).The aim of the present study was to evaluate the possible role of serum leptin as biomarker in COPD.The serum leptin levels were assessed in 58 patents with stable COPD and 21 controls applying ELISA method.The leptin levels were higher, although not significantly, in COPD patients than in controls (221.52±24.28(SE) vs. 165.04±26.01 pg/ml, p=0.197). This tendency turned out significant when only females were compared (414.60±60.63 vs. 219.40±44.15 pg/ml, p=0.038). The levels of leptin were highly dependent on the BMI both in COPD patients (p<0.001) and in controls (p=0.024): they were the highest in obese individuals and decreased with reducing the BMI.In the COPD group, women had significantly higher leptin levels than men (p<0.0001) independent of the BMI. The non-smoking patients had significantly higher leptin levels than ex-smokers (p=0.007) and current smokers (p=0.007). In patients with BMI above 25, several associations were observed: patients with mild COPD had higher serum leptin level than those with severe or very severe COPD (p=0.038); the leptin levels correlated positively with FEV1% (r= 0.304, p=0.045) and FEV1/FVC ratio (I= 0.348, p=0.021), and tended to correlate negatively with ABCD GOLD groups (Rho=-0.300, p=0.043) and with the CAT points (Rho=-0.258, p=0.091); the leptin levels below 300 ng/ml determined 4.08-fold higher risk for more severe COPD.The results of our study confirm that the serum leptin levels depend significantly on the BMI and are interfered by gender and smoking habits. However, this adipokine cannot be used as a serum biomarker for distinguishing COPD patients, but its decrease might be associated with aggravation of the disease

The Leucocyte Telomere Length, GSTM1 and GSTT1 Null Genotypes and the Risk of Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and oxidative stress both in the airways and blood and other organs. Elevated oxidative stress and inflammation have been reported to affect leucocyte telomere length (LTL). Glutathione S-transferase (GST) enzymes are a large family of xenobiotic-metabolizing enzymes that utilize different ROS products. We aimed to explore the link between GSTM1 and GSTT1 gene polymorphisms, LTL and COPD risk. For GSTM1, we genotyped 152 COPD patients and 131 non-affected controls; for GSTT1, we genotyped 149 COPD patients and 130 controls. We were able to assess TL for 91 patients and 88 controls. There was a significant difference in the GSTM1 null genotype frequency between the patients and controls (0.59 vs. 0.38, p &le; 0.000), but such was not found for GSTT1 (p = 0.192). When combining both polymorphisms, we obtained a significantly greater presence of at least one null genotype among patients (0.12 vs. 0.05, p = 0.027). An association between GSTT1 and LTL was not found. COPD patients carrying the GSTM1 null genotype had shorter telomeres compared to those carrying the non-null genotype (15,720 bp vs. 22,442 bp, p = 0.008); as for the controls, it was the opposite (31,354 bp vs. 17,800 bp, p = 0.020). The significance in both groups remained when combining GSTM1 and GSTT1 (COPD (at least one null) 16,409 bp vs. COPD (non-null) 22,092 bp, p = 0.029; control (at least one null) 29,666 bp vs. control (non-null) 16,370 bp, p = 0.027). The total glutathione level in GSTM1 non-null controls was higher compared to the null genotype (15.39 ng/mL vs. 5.53 ng/mL, p = 0.002). In COPD patients, we found no association (p = 0.301). In conclusion, according to our results, GSTM1, but not GSTT1, null genotypes might play a role in leucocyte telomere shortening, and thus be involved in the pathogenesis of COPD

Role of Single Nucleotide Polymorphism L55M in the <i>Paraoxonase 1</i> Gene as a Risk and Prognostic Factor in Acute Coronary Syndrome

The aim of the current study is to explore the possible role of L55M, (rs 854560, 163T > A) SNP as a predisposing factor for acute coronary syndrome (ACS) and to assess its potency as a prognostic biomarker for short (1 year) survival and for median (5 years) and 9-year long patients’ outcome. Methods: The current work is a prospective case-control study with 77 patients with acute coronary syndrome (53 with ST-elevation myocardial infarction, STEMI, 14 with non-ST-elevation myocardial infarction, NSTEMI and 10 with unstable angina, UA) and 122 control individuals. Patients were followed-up for 9 years. The genotyping for PON1 L55M SNP was carried on by PCR-RFLP method. Results: The results of the genotyping for PON1 L55M SNP showed a statistically significant difference (p = 0.023) between the controls and the whole group of patients with acute coronary syndrome, as the individuals with genotype with at least one variant M allele had about 2.5-fold higher risk for developing ACS than those which are homozygous of the wild-type L allele (LL genotype). In patients with variant M allele genotypes (LM + MM) which suffer from non-ST-segment elevation ACS (NSTEACS, i.e., UA or NSTEMI), the serum levels of total cholesterol (TC) and triacylglycerols (TAG) are significantly higher than in NSTEACS patients with LL genotype (p = 0.022 for TC and p = 0.015 for TAG). There was no significant difference in the survival rate at the 1st, 5th and 9th year of follow-up between ACS patients with different genotypes, although it is worth to note that in the subgroup of NSTEACS, all patients (n = 13) with variant M allele genotypes (LM + MM) were alive at the end of the first year, while 2 of the patients with LL genotype (18.2%) were dead. Conclusions: The results of our current study suggest that the variant M allele and the M allele genotypes (LM + MM) of the PON1 L55M polymorphism are risk factors for acute coronary syndrome, especially for patients with STEMI, but do not support the possible effect of this polymorphism on the clinical progression and outcome of the patients with ACS either in short or long follow-up periods

The Serum Levels of the Heavy Metals Cu, Zn, Cd, and Pb and Progression of COPD—A Preliminary Study

There is evidence in previous studies that high levels of heavy metals may play a key role in the development of COPD due to the induction of chronic inflammation and oxidative stress. In this preliminary study, we used atomic absorption spectrophotometry to measure the levels of four heavy metals (Cu, Zn, Cd, and Pb) in blood serum of COPD patients and controls over 2 years. Clinical data on disease progression or absence were collected in patients living in the industrial region of Stara Zagora, Bulgaria. The mean values of Cu in the serum of patients with COPD and the control group were 374.29 ± 15.03 μg/L and 238.55 ± 175.31 μg/L, Zn—2010.435 ± 670.006 μg/L and 1672.78 ± 934.27 μg/L, Cd—0.334 ± 0.0216 μg/L and 0.395 ± 0.110 μg/L and Pb—0.0732 ± 0.009 μg/L and 0.075 ± 0.0153 μg/L. This is probably because these elements are biogenic and are used in the body for its anti-oxidant protection. In fact, it cannot be stated with certainty that elevated levels of Cu and Zn in the environment have a negative impact in COPD patients. There was a trend towards higher levels of the toxicants lead and cadmium in COPD patients compared to the control group of patients. There is a statistically unproven trend toward higher levels of lead and cadmium in COPD patients compared to controls, which to some extent supports our hypothesis that there is a relationship between environmental lead and cadmium levels and the COPD manifested. In COPD patients, a positive correlation was found between BMI and serum Cu levels (r = 0.413, p = 0.005). A higher concentration of serum Cu was found in men with BMI ≥ 30, compared to those with BMI p = 0.019) and lead (r = 0.452; p = 0.004). The correlation of lead and cadmium with PSA also shows that these elements may also be associated with the presence of inflammatory processes. A significant negative correlation exists between Pb in the serum of patients with COPD and their blood hemoglobin (r = −356; p = 0.028). The results of our study suggest that higher doses of the trace elements Cu and Zn do not always have a negative effect in patients with COPD, while the toxicants Pb and Cd may be involved in COPD exacerbation and can be used as prognostic biomarkers for progression. Further studies are warranted to confirm these preliminary results