Modulation of periodontitis progression using pH-responsive nanosphere encapsulating metronidazole or N-phenacylthialzolium bromide.

BACKGROUND AND OBJECTIVE: This study aimed to develop pH-responsive polylactide-glycolic acid co-polymer and chitosan (PLGA/chitosan) nanosphere as an inflammation-responsive vehicle and evaluate the potential of the nanosphere encapsulating metronidazole, an antibiotic, and N-phenacylthiazolium bromide (PTB), a host modulator, for treating periodontitis. MATERIAL AND METHODS: PLGA/chitosan nanospheres were fabricated using oil-in-water emulsion method. Experimental periodontitis was induced on the rat maxillae, and the sites were randomly allocated to four treatment categories, including periodontitis alone (PR), periodontitis with nanospheres alone, nanospheres encapsulating metronidazole (MT) and nanospheres encapsulating PTB (PB). The ligature was retained until the animals were killed, and the treatment outcome was evaluated by the progression of periodontal bone loss (PPBL), inflammatory cell infiltration and collagen deposition. RESULTS: The encapsulated drug was released rapidly from the nanospheres without significant initial burst release at pH 5.5. Compared with group PR, PPBL was significantly reduced in groups MT and PB on day 4 (P<.05). On day 21, PPBL was significantly lower in group PB (P<.05). In groups MT and PB, inflammation was significantly reduced in groups MT and PB relative to groups PR and periodontitis with nanospheres alone (P<.05), and collagen deposition was significantly greater relative to group PR (P<.05). CONCLUSION: PLGA/chitosan nanospheres encapsulating metronidazole or PTB showed potential for modulating periodontitis progression.

Interleukin-10 gene promoter polymorphism and risk of liver cirrhosis.

We conducted a hospital-based case-control study to assess the association between IL-10-592 A/C, IL-10-819 C/T, and IL-10-1082 A/G polymorphisms and the risk of liver cirrhosis in a Chinese population. This 1:1-matched case-control study included 192 patients from the Chinese PLA General Hospital. Genotypes of IL-10-592 A/C, IL-10-819 C/T, and IL-10-1082 A/G were detected by polymerase chain reaction amplification-restriction fragment length polymorphism analysis. Conditional regression analysis showed that individuals carrying the IL-10-1082 G allele had an only slightly increased risk of liver cirrhosis, with an adjusted odds ratio (95% confidence interval) of 2.14 (0.97-1.68). However, we did not identify a significant association between polymorphisms in IL-10-592 A/C and IL-10-819 C/T and the risk of liver cirrhosis. These findings may provide important clues for future studies of early detection screening of liver cirrhosis.

Diabetes mellitus and risk of hepatocellular carcinoma: findings from the Singapore Chinese Health Study.

BACKGROUND: The increasing prevalence of diabetes may contribute to the rising incidence of hepatocellular carcinoma (HCC) in the US and other developed countries where HCC incidence is relatively low. Data from prospective studies on diabetes and risk of HCC in at-risk populations due to high prevalence of viral hepatitis in southeast Asia are sparse. METHODS: The Singapore Chinese Health Study is a prospective cohort of 63, 257 middle-aged and older Chinese men and women enrolled in 1993-1998. Besides an in-person interview administered to all participants at baseline, testing of serologic markers of hepatitis B or C infections were performed on a subset of cohort subjects. After a mean follow-up of 14 years, 499 cohort participants developed HCC. RESULTS: A history of diabetes at baseline was associated with a hazard ratio of 2.14 (95% confidence interval, 1.69-2.71). This statistically significant association was comparable in magnitude between men and women, and remained equally strong across strata of subjects defined by the number of years between their first clinical diagnosis of diabetes and time of enrollment in this cohort. Within a nested case-control set of cohort subjects tested for serological markers of hepatitis B or C infections, the diabetes-HCC association was found to be present mainly among those devoid of any markers. CONCLUSION: A history of diabetes at baseline is highly associated with non-viral HCC. Future studies are warranted to elucidate the biological mechanism underpinning the role of diabetes in nonviral-related hepatocarcinogenesis.

Smoking as an independent risk factor for hepatocellular carcinoma: the Singapore Chinese Health Study.

BACKGROUND: Given the close correlation between smoking and alcohol intake in most epidemiologic studies, it is difficult to exclude the residual confounding effect of alcohol in the association between smoking and hepatocellular carcinoma (HCC). METHOD: We evaluated the association between smoking and risk of HCC in the Singapore Chinese Health Study, a prospective cohort with a low prevalence of alcohol intake. Information on cigarette smoking and alcohol consumption was obtained through in-person interviews conducted at enrolment. RESULTS: After a mean of 11.5 years of follow-up, there were 394 incident cases of HCC. Participants who consumed more than two alcoholic drinks per day showed an increased risk for HCC (hazard ratio (HR)=2.24; 95% confidence interval (CI)=1.46-3.41). After adjusting for alcohol consumption and other potential confounders, current vs never smokers had a statistically significant, increased risk of HCC (HR=1.63; 95% CI=1.27-2.10) that was dose-dependent (number of cigarettes per day, P for trend<0.001). The observed tobacco-HCC association also was duration-dependent (years of smoking in ever smokers, P for trend=0.002). When we excluded daily drinkers from the analysis, all risk estimates remained essentially the same and statistically significant. CONCLUSION: Our findings strongly implicate tobacco smoke as a causal factor of HCC development.

Clinical and microbiological characteristics of urine culture-confirmed genitourinary tuberculosis at medical centers in Taiwan from 1995 to 2007.

All patients with urine culture-confirmed genitourinary tuberculosis (GUTB) diagnosed between 1995 and 2007 at two medical centers in northern Taiwan were included in this retrospective study. Genotypes of 48 preserved Mycobacterium tuberculosis (MTB) isolates from these patients were determined by spoligotyping and double repetitive element PCR (DRE-PCR) analysis. Among the 64 patients, 38 (59.4%) were male with a mean ±SD age of 60.3 ± 16.1 years old. The overall mortality rate was 26.2%. Poor prognostic factors included age over 65 years (HR = 4.03; 95%; CI: 1.27-12.76), cardiovascular disease (HR = 5.96; 95% CI: 1.98-17.92), receiving steroids (HR = 10.16; 95% CI: 2.27-45.47), not being treated (HR 4.81; 95% CI 1.12-20.67). Spoligotyping and DRE-PCR of the 48 MTB isolates revealed that 20 (41.7%) belonged to the Beijing family and 40 (83.3%) had a clustering pattern. Identification of a Beijing family isolate was not correlated with drug resistance or mortality. Clustering strains were likely to be resistant to isoniazid (OR = 4.71; 95% CI: 1.10 to 23.53). In this study of patients with urine culture-confirmed GUTB, age and coexisting diseases were independently associated with an unfavorable outcome. The Beijing family was the dominant genotype of GUTB isolates, but did not correlate with drug resistance or outcome.

Evidence of an X-linked or recessive genetic component to prostate cancer risk.

We used data from a population-based cohort study of blacks, Hispanics, Japanese and whites to examine the frequency of prevalent prostate and breast cancer by family history status of first-degree relatives (parents and siblings). Independent of race, the age-adjusted relative risk for prevalent prostate cancer in subjects with affected brothers was approximately two times that in subjects with affected fathers (P < 0.00005). No such excess risk for breast cancer was observed among subjects with affected sisters compared to those with affected mothers (age- and race-adjusted relative risk = 1.10, P = 0.34). The magnitude of the relative risk for prostate cancer in sibling- versus parent-affected groups was significantly different from that of the comparable relative risk for breast cancer (P < 0.00005). An excess risk of prostate cancer in men with affected brothers compared to those with affected fathers is consistent with the hypothesis of an X-linked, or recessive, model of inheritance.

Plasma carotenoids and risk of acute myocardial infarction in the Singapore Chinese Health Study.

BACKGROUND AND AIM: Modification of low-density lipoprotein due to oxidative stress is essential in the development of coronary atherosclerosis. Data of specific carotenoids except ß-carotene on cardioprotective effects in humans are limited. METHODS AND RESULTS: This study examined the associations between plasma concentrations of specific carotenoids and incidence of acute myocardial infarction. The study included 280 incident cases of acute myocardial infarction and 560 matched controls nested within the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese men and women aged 45-74 years old enrolled in 1993-1998 in Singapore. Retinol and carotenoids in prediagnostic plasma were quantified using high-performance liquid chromatography. High levels of plasma ß-cryptoxanthin and lutein were associated with decreased risk of acute myocardial infarction after adjustment for multiple risk factors for coronary heart disease. For ß-cryptoxanthin, the odds ratio (95% confidence interval) for the highest (Q5) versus the lowest (Q1) quintile was 0.67 (0.37-1.21) (P for trend=0.03). For lutein, the odds ratios (95% confidence intervals) for the combined Q2-Q3 and the combined Q4-Q5 versus Q1 were 0.71 (0.45-1.12) and 0.58 (0.35-0.94) respectively (P for trend=0.03). There was no statistically significant association between other carotenoids or retinol and risk of acute myocardial infarction. CONCLUSIONS: High plasma levels of ß-cryptoxanthin and lutein were associated with decreased risk of acute myocardial infarction. The findings of this study support a cardioprotective role of these two carotenoids in humans.

[Progress of researches on serine protease inhibitors for zoonotic cestode family Taeniidae].

Serine protease inhibitor, a protein superfamily that inhibits the serine protease activity, protects hosts from parasitic infections. This review describes the spatial structure and classification of serine protease inhibitor, mechanisms underlying the interplay between serine protease inhibitor and host immune responses and current advances in serine protease inhibitor of zoonotic cestode family Taeniidae, so as to provide insights into the diagnosis of zoonotic tapeworm infections, discovery of therapeutic targets and screening of vaccine candidates.

Clinical benefits of routine examination and synchronous repair of occult inguinal hernia during laparoscopic peritoneal dialysis catheter insertion: a single-center experience.

PURPOSE: Occult inguinal hernias (IH) predispose peritoneal dialysis (PD) patients to the symptomatic IH formation after starting PD, which may cause complications. We conducted a retrospective study to assess the benefit/risk profile of routine laparoscopic examination for occult IH (RLEOH) with a synchronous repair in patients receiving PD catheter placement. METHODS: 432 patients were enrolled in this study. Patients with an internal hernia sac at all sizes were deemed to have occult IH. We retrospectively reviewed data including demographic characteristics and operative details. We also measured incidence rates of symptomatic IH, metachronous IH repair, and catheter survival over a follow-up period after starting PD. RESULTS: These patients were classified into the RLEOH group (n = 365) and the non-RLEOH group (n = 67). The RLEOH group was subdivided into occult IH with a synchronous repair (n = 17; the subgroup A), no occult IH (n = 339; the subgroup B), and occult IH without a synchronous repair (n = 9; the subgroup C). The incidence rates of symptomatic IH developed after staring PD in subgroups A, B, and C were 0, 5.6, and 22.2%, respectively, whereas that in the non-RLEOH group was 13.4%. The RLEOH group had a reduced hazard ratio for metachronous IH repair compared with the non-RLEOH group (HR = 0.426; 95% CI 0.195-0.930, p = 0.032). None of our patients suffered from herniorrhaphy-related complications. CONCLUSION: RLEOH with a synchronous repair during PD catheter insertion confers clinical benefits in reducing the risk of developing IH after starting PD and the need for a metachronous repair. This is a safe and reasonable approach.

Body mass index and smoking-related lung cancer risk in the Singapore Chinese Health Study.

BACKGROUND: Smokers with low body mass index (BMI) may be more susceptible to lung cancer. METHODS: We prospectively examined the association between baseline BMI and lung cancer risk in the Singapore Chinese Health Study, a cohort of 63 257 Chinese enrolled between 1993 and 1998. RESULTS: After adjustment for smoking intensity and duration, BMI was inversely associated with risk of lung cancer among current smokers (P for trend=0.0004). Current smokers at different dosage of smoking with low BMI had significantly higher risk for lung cancer than those with high BMI. Hazard ratios (95% confidence intervals) of lung cancer for heavy smokers with BMI of > or =28, 24-<28, 20-<24, and <20 kg m(-2) were 6.37 (2.10-19.30), 9.01 (5.04-16.10), 8.53 (6.35-11.5), and 11.12 (6.60-18.70), respectively, as compared with nonsmokers. BMI had no modifying effects on lung cancer risk among nonsmokers and former smokers. CONCLUSION: Smokers with lower BMI may experience an enhanced risk of lung cancer. The findings have significant public-health implication given the increase in smoking prevalence in developing countries, where people still have relatively low BMI.

Smoking cessation and lung cancer risk in an Asian population: findings from the Singapore Chinese Health Study.

BACKGROUND: Smoking cessation is an important strategy for reducing the harmful effects of tobacco, particularly in the prevention of lung cancer; however, prospective data on the impact of smoking cessation on lung cancer risk in Asian populations are limited. METHODS: We studied a population-based cohort of Chinese men and women aged 45-74 years--participants of the Singapore Chinese Health Study. Information on smoking, lifestyle and dietary habits was collected at the time of recruitment in 1993-1998; and smoking status was assessed again at a second interview in 1999-2004 (mean interval 5.8 years). Participants were followed up to 31 December 2007, and incident cases of lung cancer were ascertained by linkage with population-wide registries. RESULTS: Among 45,900 participants, there were 463 incident cases of lung cancer. Relative to current smokers, those who quit smoking subsequent to baseline assessment had a 28% decrease in the risk of lung cancer (adjusted hazard ratio (HR) 0.72; 95% CI (95% confidence interval): 0.53-0.98). The risk was less than half in ex-smokers who had quit before the first interview and maintained their status (HR 0.42; 95% CI: 0.32-0.56). CONCLUSIONS: Reduction in lung cancer incidence with smoking cessation in Asian populations is substantial and can be observed within a few years after quitting.

Right hepatectomy by the anterior method with liver hanging versus conventional approach for large hepatocellular carcinomas.

BACKGROUND: The aim was to compare short-term results of right hepatectomy using the anterior approach (AA) and liver hanging manoeuvre with the conventional approach (CA) for large hepatocellular carcinoma (HCC). METHODS: This was a retrospective review of 71 consecutive patients with HCC at least 5 cm in diameter who underwent curative right hepatectomy using either the AA with the liver hanging manoeuvre (33) or the CA (38) between January 2004 and December 2008. Clinical data, operative results and survival outcomes were analysed. RESULTS: The groups had similar clinical, laboratory and pathological parameters. The AA group had larger tumours than the CA group (P = 0.039), but comparable grade and stage distribution. The operative results were similar except for an increased blood transfusion requirement with the conventional procedure (P = 0.001). The AA group had a lower recurrence rate (P = 0.003) and better disease-free survival (DFS) (P = 0.001) than the CA group, but overall survival rates were not significantly different (P = 0.091). Presence of tumour encapsulation, absence of tumour microvascular invasion and AA were predictive of DFS, whereas tumour stage was the only independent predictor of overall survival. CONCLUSION: The AA right hepatectomy with liver hanging manoeuvre for large HCC is associated with reduced blood transfusion requirement and lower recurrence rates in the short term.

Brain tumors in children and occupational exposure of parents.

Ninety-two cases of brain tumor in children less than 10 years old were compared with 92 matched controls for parental occupational history. Cases were more likely than controls to show material occupations involving chemical exposure, paternal occupations involving solvents, and employment of father in the aircraft industry. These three factors were not affected by adjustment for the potential confounding variables examined in this study.

Tuberculosis outcomes in Taipei: factors associated with treatment interruption for 2 months and death.

SETTING: All individuals reported as being treated for pulmonary tuberculosis (PTB) among citizens of Taipei City, Taiwan, in 2003. OBJECTIVES: To investigate risk factors associated with treatment interruption for at least 2 consecutive months and death. DESIGN: The outcome of PTB cases was determined by consulting medical charts. RESULTS: Of 1127 PTB patients registered, 824 (73.1%) were successfully treated, 189 (16.8%) died, 65 (5.8%) interrupted treatment, 17 (1.5%) were still on treatment 15 months after commencing treatment and 32 (2.8%) failed. The only significant factor associated with treatment interruption was visits to other health facilities after commencing tuberculosis (TB) treatment. TB patients had a standardised mortality ratio of 8.7 (95%CI 7.5-10.0). Factors significantly associated with death were age (adjusted hazard ratio [adjHR] 1.06. 95%CI 1.05-1.08), sputum culture not performed/unknown (adjHR 2.07, 95%CI 1.47-2.92), and comorbidity with respiratory disease (adjHR 1.68, 95%CI 1.24-2.27), infectious disease (adjHR 2.80, 95%CI 2.07-3.78), renal disease (adjHR 2.58, 95%CI 1.82-3.66) or cancer (adjHR 3.31, 95%CI 2.35-4.65), compared with other patients. CONCLUSION: Visits to other health facilities were associated with interruption of treatment for at least 2 months. A high proportion of deaths was due to old age and comorbidity.

Insulin-like growth factor-1 promoter polymorphisms and colorectal cancer: a functional genomics approach.

RATIONALE: Insulin-like growth factor-1 (IGF1) has been proposed to mediate the obesity-related carcinogenic effects of "Western lifestyle". While genetic factors explain at least half of inter-individual IGF1 variation, the IGF1 polymorphisms hypothesised to underlie the variation in cancer incidence rates remain ill-defined. METHODS: We used a comparative genomics approach to identify putative regulatory polymorphisms in the IGF1 promoter region within a rapidly westernising population, the Singapore Chinese. Association of IGF1 genotype with colorectal cancer risk was assessed among 298 colorectal cancer cases and 1142 controls nested within the Singapore Chinese Health Study. RESULTS: We identified a common (minor allele frequency = 0.36) single-nucleotide polymorphism (SNP), IGF1-2995 C/A, within a consensus domain for an octamer binding factor (Oct1/Oct2) transcription factor binding site. Possession of one or two copies of the minor allele (genotypes AA and CA) conferred an approximate 40% decrease in risk in comparison to genotype CC (odds ratio, 0.59; 95% confidence interval, 0.45 to 0.77). This association was stronger for colon cancer than for rectal cancer (p(heterogeneity)<0.001) and for those who were physically active versus inactive (p(interaction) = 0.05). Models including other previously identified promoter polymorphisms did not provide a better prediction of colorectal cancer risk. CONCLUSIONS: Our results support the hypotheses that IGF1 plays a role in colonic carcinogenesis and that genetically inherited variation in IGF1 expression influences risk of colorectal cancer.

Prospective study of dietary patterns and colorectal cancer among Singapore Chinese.

An influence of Western diet and lifestyle factors observed among Singapore Chinese may contribute to the population's marked rise in colorectal cancer incidence over the past two decades. Thus far, however, there is little evidence for individual nutrients and foods as major contributing factors in this population. We evaluated whether patterns of food intake were associated with colorectal cancer in a population-based cohort of 61,321 Singapore Chinese that was established in 1993-98. Two dietary patterns, meat-dim sum and vegetable-fruit-soy, were previously identified by principal components analysis using baseline dietary data from a validated 165-item food frequency questionnaire. As of 31 December 2005, 961 incident colorectal cancer cases were diagnosed. Proportional hazards regression was used to calculate adjusted hazard ratios. Using nearly 10 years of follow-up data, we observed no association with either the meat-dim sum or vegetable-fruit-soy pattern for colorectal cancer. In conclusion, neither individual nutrients or foods nor dietary patterns appear to explain the rise in colorectal cancer among Singapore Chinese population.

Soy intake and breast cancer risk in Singapore Chinese Health Study.

We investigated the effects of soy isoflavone intake on breast cancer in a prospective study of 35,303 Singapore Chinese women enrolled during April 1993 to December 1998 in the Singapore Chinese Health Study. At recruitment, each subject was personally administered a validated semiquantitative food frequency questionnaire covering 165 food and beverage items. As of December 31,2005, 629 had developed breast cancer following an accumulation of 338,242 person-years. Using Cox regression and adjusting for age at interview, year of interview, dialect group, education, family history of breast cancer, age when periods became regular, parity, menopausal status, body mass index (BMI), n-3 fatty acid, and other covariates, we found breast cancer risk was reduced significantly in association with high soy intake. Relative to women with lower (below median) soy intake (<10.6 mg isoflavone per 1000 Kcal), women with higher (above median) intake showed a significant 18% risk reduction (relative risk (RR)=0.82, 95% confidence interval (CI)=0.70-0.97). This inverse association was apparent mainly in postmenopausal women (RR=0.74, 95% CI=0.61-0.90), and was not observed in premenopausal women (RR=1.04, 95% CI=0.77-1. 40). Among postmenopausal women, the soy-breast cancer association was stronger in those above median BMI (RR=0.67, 95% CI=0.51-0.88) than in leaner women (RR=0.83, 95% CI=0.62-1.11). Duration of follow-up modified the soy-breast cancer association, the effect being twice as large among women with 10+ vs fewer years of follow-up. Neither oestrogen nor progesterone receptor status of the tumours materially influenced the association. These prospective findings suggest that approximately 10 mg of isoflavones per day, obtained in a standard serving of tofu, may have lasting beneficial effects against breast cancer development.

Suspect the donor with potential infection in the adult deceased donor liver transplantation.

INTRODUCTION: Liver transplantation is the treatment of choice for end-stage liver disease. However, the shortage of donors is still the major problem in most Asian countries. Using extended donor criteria may maximize the deceased donor pool, but some high-risk donors may show adverse recipient outcomes due to preexisting infection. MATERIALS AND METHODS: This study included deceased donor liver transplant patients from June 2002 through June 2007. We retrospectively reviewed the clinical manifestations of donors and recipients. The donors showed no definite infection at the time the organs were matched to the recipients. Routine sputum, urine, blood, and bile cultures were obtained from the donor during the perioperative period. According to the final reports of the cultures, the recipients divided into two groups: donor infection (DI) and no donor infection (NDI). RESULTS: This study included 59 donor and 72 recipients, including 34 who received a graft from a donor with a positive culture (47.2%) finally, defined as the DI groups, and 38 recipients (52.8%) as the NDI group. Most of them had positive sputum cultures, followed by urine cultures. Staphylococcus aureus was the most common pathogen. Using a stepwise logistical regression model to analyze the significant donor characteristics, donor admission to the intensive care unit (ICU) for 7 days or longer (P < or = .0001), previous cardiopulmonary cerebral resuscitation (CPCR) (P = .036), and inotropic agents (P = .022) were the only three independent factors to predict donor infection. To compare the outcomes between DI and NDI groups, the days of recipient ICU or hospital admission, the 1-week or 1-month mortality rate, and the overall survival showed no significant difference between both groups. However, the hospital mortality rate was mildly higher in the DI group (P = .050). CONCLUSION: Donors with prolonged ICU admissions, rescue by CPCR, and use of inotropic agents carried an high risk of potential infections. Our data did not show a significant increase in adverse outcomes if the recipient received a graft from a potentially infected donor. However, there may be an increased risk of hospital mortality. We should be careful in using these potentially infected donors in selective recipients.

Quantitative analysis of associations between DNA hypermethylation, hypomethylation, and DNMT RNA levels in ovarian tumors.

How hypermethylation and hypomethylation of different parts of the genome in cancer are related to each other and to DNA methyltransferase (DNMT) gene expression is ill defined. We used ovarian epithelial tumors of different malignant potential to look for associations between 5'-gene region or promoter hypermethylation, satellite, or global DNA hypomethylation, and RNA levels for ten DNMT isoforms. In the quantitative MethyLight assay, six of the 55 examined gene loci (LTB4R, MTHFR, CDH13, PGR, CDH1, and IGSF4) were significantly hypermethylated relative to the degree of malignancy (after adjustment for multiple comparisons; P < 0.001). Importantly, hypermethylation of these genes was associated with degree of malignancy independently of the association of satellite or global DNA hypomethylation with degree of malignancy. Cancer-related increases in methylation of only two studied genes, LTB4R and MTHFR, which were appreciably methylated even in control tissues, were associated with DNMT1 RNA levels. Cancer-linked satellite DNA hypomethylation was independent of RNA levels for all DNMT3B isoforms, despite the ICF syndrome-linked DNMT3B deficiency causing juxtacentromeric satellite DNA hypomethylation. Our results suggest that there is not a simple association of gene hypermethylation in cancer with altered DNMT RNA levels, and that this hypermethylation is neither the result nor the cause of satellite and global DNA hypomethylation.