Association of HLA-DRB1*13 and TNF-alpha gene polymorphisms with clearance of chronic hepatitis B infection and risk of hepatocellular carcinoma in Thai population

Considerable evidence suggests that host genetic factor play an important role in the pathogenesis and clinical outcome of chronic hepatitis B virus (HBV) infection in several ethic groups. Association study was performed included 150 chronic HBV patients, 100 resolved hepatitis B and 150 healthy individuals with similar ethic background. Interestingly, human leucocyte antigen (HLA)-DR13 show a strong association with the clearance of HBV [odds ratio (OR) = 0.04, 95% confidence interval (CI) = 0.00-0.26, corrected P-value (P(c)) = 0.0008] similar to reports from several ethic groups. TNF-alpha promoter polymorphisms (-863, -308 and -238) were also analysed. Only -863 C allele was found to be significantly decreased in chronic HBV patients compared with healthy control (P(c) = 0.03, OR = 0.54, 95% CI = 0.35-0.84 respectively). This -863C allele was not in linkage disequilibrium with HLA-DR13 suggesting that other genetic markers linked with -863C might influence clearance of chronic HBV infection in Thai. When stratified chronic HBV patients into patients without hepatocellular carcinoma (HCC) and with HCC, the -863 A allele was significantly increased in the HCC group compared to healthy control (P(c) = 0.003, OR = 2.61, 95% CI = 1.49-4.60). Haplotype analysis (-863/-308/-238) revealed that the homozygosity of the haplotype (CGG/CGG) was a protective marker for HCC (OR = 0.37, 95% CI = 0.17-0.79, P(c) = 0.02). One can propose that carriers of -863A genotype are associated with increased levels of TNF-alpha in the liver in response to HBV infection and induce hapatocyte damage that may finally lead to HCC development. Additional study is needed to validate these finding and to further explore the genetic pathogenesis of HBV infection.     

Anti-inflammatory activity of lansais from endophytic Streptomyces sp. SUC1 in LPS-induced RAW 264.7 cells

This research was undertaken to find the in vitro inflammatory action of lansai A–D produced by Streptomyces sp. SUC1. We investigated the effects of lansai C not only on the formation of nitric oxide (NO), prostaglandin E₂ (PGE₂), tumour necrosis factor (TNF-α), interleukin (IL)-1α, IL-6 and IL-10, but also on inducible NO synthase and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells. The data obtained were consistent with the modulation of inducible nitric oxide synthase enzyme expression. A similar fashion was also observed when LPS-induced PGE₂ release and COX-2 expression were tested. The significant inhibitory effects were shown in concentration-dependent manners. In addition, lansai C also mildly but significantly reduced the formation of TNF-α. These findings support the application of lansai C as anti-inflammatory agent.     

Cigarette smoking and its relation to pulmonary tuberculosis in adults

The purpose of this hospital-based case-control study is to determine the effect of passive and active smoking on pulmonary TB in adults. The study subjects were 100 new pulmonary TB cases diagnosed at TB Division, and age-sex matched 100 non-TB cases from patients admitted to Taksin Hospital and healthy subjects who came for annual physical check-up at either the outpatient clinic of the TB division or Taksin Hospital, during May 2001 to October 2001. All subjects had blood tests and only persons who were HIV-negative, DM-negative and free of other lung diseases were included. Data were collected by direct interview using questionnaires. Multivariate analysis of cigarette smoking related to pulmonary TB in adults was performed. The factors related to pulmonary TB in adults were current active smoking regardless of passive smoking exposure. There was a significant association between early age at initiation of smoking and TB. Active (current + ex-active) smokers who started smoking at age 15-20 years had a higher risk of pulmonary TB compared to others (OR = 3.18, 95% CI = 1.15-8.77); as well as the long duration of smoking: persons who had smoked >10 years had a higher risk of pulmonary TB (OR = 2.96, 95% CI = 1.06-8.22). There was a relationship between pulmonary TB and the amount of smoking exposure. Those who smoked >10 cigarettes/day (OR = 3.98, 95% CI = 1.26-12.60) or >3 days/week (OR = 2.68, 95% CI = 1.01-7.09) had higher risk of pulmonary TB compared to non-smokers. Passive smokers who were exposed to tobacco smoke >3 times/week outside the home had a higher risk of pulmonary TB than those with exposure < or =3 times/week (OR = 3.13, 95% CI = 1.07-9.17). It was also found that the effects of passive smoking in the office and/or neighborhood were strong. Persons with such exposures had a higher risk of pulmonary TB than no exposure or exposure < or =3 times/week from either or both places (OR = 4.62, 95% CI = 1.68-14.98). Therefore, an effective anti-smoking campaign is expected to have a positive repercussion on TB incidence. Smoking cessation must be considered and promoted by all levels of health care providers.     

A new phenolic compound with anticancer activity from the wood of Millettia leucantha

A new phenolic compound, 1-(3-hydroxy-4-methoxyphenyl)-3-(2,4-dihydroxy-5-methoxyphenyl) propan-1-ol, named as millettinol (1), along with six known compounds, medicarpin (2), 4-hydroxy-3-methoxy-8,9-methylenedioxypterocarpan (3), 5,4'-dihydroxy-7,8-dimethoxyisoflavone (4), physcion (5), (R)-(-)-mellein (6) and isoliquiritigenin (7), were isolated from the wood of Millettia leucantha. The structures of the compounds were determined by an analysis of their spectroscopic data. Some of the isolates were tested for anticancer activity. Compound 1 exhibited strong cytotoxicity against the BCA-1 tumor cell lines with an IC(50) = 3.44 μg/mL.     

RETRACTED: Anti-inflammatory Activity of 4-Arylcoumarins from Endophytic Streptomyces aureofaciens CMUAc130 in Murine Macrophage RAW 264.7 Cells

Forty-seven patients with various connective tissue disorders were studied to evaluate the spontaneous release of lymphocyte factors affecting the in vitro migration of guinea pig macrophages. In the assay used the lymphocytes from 8 patients produced an excessive amount of factors inhibiting macrophage migration while the lymphocytes from 12 patients produced an enhancement of migration. There were no differences in the delayed hypersensitivity skin test responses between the 2 groups of patients. The data are consistent with either an abnormality of suppressor lymphocyte function or an altered lymphocyte subpopulation relationship as a factor in this in vitro abnormality.     

Interleukin-1β gene polymorphism associated with hepatocellular carcinoma in hepatitis B virus infection

AIM: To examine the effect of interleukin-1-beta (IL-1beta) promoter region C-511T and IL-1 receptor antagonist (IL-1RN) polymorphism among the patients with chronic hepatitis B virus (HBV) infection (HCC and non-HCC). METHODS: Genomic DNA from 136 Thai patients with chronic HBV infection (HCC=46 and non-HCC=90) and 152 healthy individuals was genotyped for IL-1beta gene polymorphism (-511) using polymerase chain reaction with sequence specific primers (PCR-SSP). The variable number of tandem repeats (VNTR) of IL-1RN gene was assessed by a PCR-based assay. The association between these genes and status of the disease was evaluated by chi2 test. RESULTS: IL-1B-511 genotype C/C was found to be significantly different in patients with HCC when compared with healthy individuals (P=0.036, OR=2.29, 95%CI=1.05-4.97) and patients without HCC (P=0.036, OR=2.52, 95%CI=1.05-6.04). Analysis of allele frequencies of IL-1B-511 showed that IL-1B-511 C allele was also significantly increased in patients with HCC, compared to that in healthy control (P=0.033, OR=1.72, 95%CI=1.04-2.84). However, no significant association in IL-1RN gene was found between the two groups. CONCLUSION: IL-1B-511C allele, which may be associated with high IL-1B production in the liver, is a genetic marker for the development of HCC in chronic hepatitis B patients in Thai population.     

Anti-inflammatory activity of 4-arylcoumarins from endophytic Streptomyces aureofaciens CMUAc130 in murine macrophage RAW 264.7 cells

This research was undertaken to test the in vitro anti-inflammatory action of 5,7,4'-trimethoxy-4-phenylcoumarin and 5,7-dimethoxy-4-phenylcoumarin produced by Streptomyces aureofaciens CMUAc130. The effects of the two coumarins were investigated on the formation of NO, PGE2, and TNF-alpha and also on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells. The data obtained were consistent with the modulation of iNOS enzyme expression. A similar effect was also observed when LPS-induced PGE2 release and COX-2 expression were tested. The inhibitory effects were shown in concentration-dependent manners. The 5,7,4'-Trimethoxy-4-phenylcoumarin and 5,7-dimethoxy-4-phenylcoumarin also mildly but significantly reduced the formation of TNF-alpha.