Cathelicidin (LL-37) and its correlation with pro-oxidant, antioxidant balance and disease activity in systemic lupus erythematosus: a cross-sectional human study.

Background Cathelicidin (LL-37), an endogenous antimicrobial peptide, has recently been involved in the pathogenesis of autoimmune diseases. To assess whether LL-37 reflects disease activity, we measured serum levels of it in systemic lupus erythematosus (SLE) patients with active and inactive disease compared to healthy controls. LL-37 was also compared between new and old cases. Moreover, the correlation of LL-37 and pro-oxidant, antioxidant balance (PAB) was measured. Methods The study population consisted of 50 SLE patients and 28 healthy controls. Of those, 39 patients had active and 11 patients had inactive disease. Serum levels of LL-37 were measured by ELISA and PAB values by a special method. Results There was no difference in levels of LL-37 between patients and healthy controls (50.9 ± 20.8 vs. 67.7 ± 43.3 ng/ml, P = 0.31). LL-37 did not correlate with SLEDAI and its items in total patients. LL-37 had a positive correlation with SLEDAI in active patients ( P = 0.01, r = 0.4). In active patients (78% of patients), multivariate regression analysis showed significant negative correlation between LL-37 and C3 ( P = 0.01, standardized beta -0.50). No difference was found in levels of PAB between patients and controls (90.4 ± 34.1 vs. 86.9 ± 25.6 HK, P = 0.4).There was no difference in the levels of PAB between patients with active and inactive disease (93.2 ± 34.1 vs. 80.2 ± 33.7 HK, P = 0.27). No correlation was found between levels of PAB and SLEDAI items and total score. However, a positive correlation between the levels of LL-37 and PAB in SLE patients was found ( r = 0.3, P < 0.01). Conclusion Based on this study, serum LL-37 and PAB did not increase in lupus compared with healthy individuals. LL-37 serum values rose in parallel with SLEDAI in active disease. Positive correlation between serum PAB and LL-37 could be a great achievement of this study that may suggest the role of antioxidants in controlling NETosis.

Predictors of survival in oesophageal cancer patients in a high-risk area in Northern Iran: the role of health services utilisation.

We aimed to determine predictors of survival in oesophageal cancer (EC) patients in a high-risk area. This study was conducted on EC patients diagnosed in 2007-2008 in Golestan province, Iran. Diagnostic (DU) and Therapeutic (TU) services utilisation indices were determined. DU and TU indices of 1 were considered as good utilisation. EC-specific survival rates were calculated. Multivariate Cox-regression model was used to calculate adjusted hazard ratios (AHRs). Two hundred and twenty-three EC subjects were enrolled. The median survival time was 10.47 months and the 5-year survival rate was 11%. Cox-regression analysis suggested that stage of tumour (AHRregional  = 3.75, 95% confidence interval [CI]: 2.34-6.00; AHRmetastasis  = 12.21, 95% CI: 7.42-20.08) and TU (AHR = 1.78, 95% CI: 1.25-2.52) were the strongest variables related to EC survival. The median survival time in patients with good and poor TU were 14.37 and 8.53 months respectively (p < .01). There was no significant relationship between DU and EC survival. We found relatively low survival rates in our EC patients when compared with developed countries. Our results also suggested an increasing trend for EC survival rate during recent years. Good TU could predict higher survival rates. Patients' access to therapeutic services may be considered as an important indicator in decision-making for controlling EC.

Determinants of healthcare utilisation and predictors of outcome in colorectal cancer patients from Northern Iran.

We aimed to assess healthcare utilisation (HU), its determinants, as well as its relationship with survival in colorectal cancer (CRC) patients. This study was conducted on incident CRC cases from Northern Iran. Information on HU was collected using a valid questionnaire, considering eight diagnostic and four therapeutic services. The results were categorised as good and poor HU. Multivariate logistic regression analysis was used to assess the relationship between HU and other variables. Cox regression analysis was performed to determine major predictors of survival. In total, 227 new cases of CRC were enrolled. HU could be assessed in 218 subjects (96%). Living in rural areas was the strongest variable related to poor HU (adjusted OR, odds ratio = 2.65; CI, confidence interval: 1.30-5.40). The median survival time was 40.5 months. The 1-, 3- and 5-year survival rates were 71%, 52% and 44% respectively. Cox regression analysis showed a significant lower survival rate in patients with poor HU (HR = 2.3; CI: 1.46-3.64). HU was an independent predictor of survival in our CRC patients. Patients' place of residence was a significant determinant of HU. Regarding its effects on patients' outcome, HU and its determinants should be considered in designing CRC controlling programmes in our region and similar high-risk populations.

Identification of novel genes involved in gastric carcinogenesis by suppression subtractive hybridization.

Gastric cancer (GC) is one of the most common and life-threatening types of malignancies. Identification of the differentially expressed genes in GC is one of the best approaches for establishing new diagnostic and therapeutic targets. Furthermore, these investigations could advance our knowledge about molecular biology and the carcinogenesis of this cancer. To screen for the overexpressed genes in gastric adenocarcinoma, we performed suppression subtractive hybridization (SSH) on gastric adenocarcinoma tissue and the corresponding normal gastric tissue, and eight genes were found to be overexpressed in the tumor compared with those of the normal tissue. The genes were ribosomal protein L18A, RNase H2 subunit B, SEC13, eukaryotic translation initiation factor 4A1, tetraspanin 8, cytochrome c oxidase subunit 2, NADH dehydrogenase subunit 4, and mitochondrially encoded ATP synthase 6. The common functions among the identified genes include involvement in protein synthesis, involvement in genomic stability maintenance, metastasis, metabolic improvement, cell signaling pathways, and chemoresistance. Our results provide new insights into the molecular biology of GC and drug discovery: each of the identified genes could be further investigated as targets for prognosis evaluation, diagnosis, treatment, evaluation of the response to new anticancer drugs, and determination of the molecular pathogenesis of GC.

Pilot study of cytological testing for oesophageal squamous cell dysplasia in a high-risk area in Northern Iran.

BACKGROUND: Oesophageal squamous cell carcinoma (ESCC) is a fatal disease with 5-year survival rates of <5% in Northern Iran. Oesophageal squamous dysplasia (ESD) is the precursor histologic lesion of ESCC. This pilot study was conducted to assess the feasibility, safety, and acceptability of non-endoscopic cytological examination of the oesophagus and to provide initial data on the accuracy of cytological atypia for identifying patients with ESD in this very-high-risk area. METHODS: Randomly selected asymptomatic participants of the Golestan Cohort Study were recruited. A cytological specimen was taken using a capsule sponge device and evaluated for atypical cells. Sections of the cytological specimen were also stained for p53 protein. Patient acceptability was assessed using a visual analogue scale. The cytological diagnosis was compared with a chromoendoscopic examination using Lugol's solution. RESULTS: Three hundred and forty-four subjects (43% male, mean (s.d.) age 55.6 (7.9) years) were referred to the study clinic. Three hundred and twelve met eligibility criteria and consented, of which 301 subjects (96.5%) completed both cytological and endoscopic examinations. There were no complications. Most of the participants (279; 92.7%) were satisfied with the examination. The sensitivity and specificity of the cytological examination for identifying subjects with high-grade ESD were 100 and 97%, respectively. We found an accuracy of 100% (95% CI=99-100%) for a combination of cytological examination and p53 staining to detect high-grade ESD. CONCLUSIONS: The capsule sponge methodology seems to be a feasible, safe, and acceptable method for diagnosing precancerous lesions of the oesophagus in this population, with promising initial accuracy data for the detection of high-grade ESD.

Aflatoxin contamination in wheat flour samples from golestan province, northeast of iran.

BACKGROUND: Due to the high toxicity of aflatoxin and its effects on public health, determination of aflatoxin level in Wheat flour samples in the Golestan province, north of Iran was investigated. To examine the effect of seasonal changes, summer and winter sampling was performed with standard sampling methods. METHODS: A total of 200 flour samples were collected from 25 factories. HPLC method with immunoaffinity chromatography was used to measure aflatoxin types (G2, G1, B2 and B1). Statistical analysis was performed by the Pearson correlation test, One-way ANOVA and multivariate regression analysis. RESULTS: Mean total aflatoxin levels of samples were 0.82 and 1.99 ng/g in summer and winter, respectively. Aflatoxin B1 levels were detected in 3.1%, 7.4% over permissible limits by worldwide regulations in samples collected in summer and winter, respectively. Aflatoxins in winter were higher than summer. The highest frequency of aflatoxin contamination in winter was B2 (98%) and in summer G1 (51%). The relationship between humidity and rate of aflatoxin B1 and total aflatoxin was significant in winter. Results of multivariate regression were showed the strongest relationship with humidity and aflatoxin level. Despite the contamination of flour samples, there was no contamination higher than the standard limit of Iran Standard Institute. But it was significantly higher than similar studies from other regions. CONCLUSIONS: Therefore, with regard to negative impacts of aflatoxin on health, aflatoxin contamination should be considered in future programs. Decrease of aflatoxin contamination may be made practical through reducing wheat storage duration and controlling humidity.