Modulation of host matrix metalloproteinases by bacterial virulence factors relevant in human periodontal diseases

OBJECTIVE: Bacterial pathogens involved in periodontal diseases exert a part of their destructive effect by triggering and inducing host cells to elevate their secretion of matrix metalloproteinases (MMPs). Pathogen-secreted phospholipase (PLC) is one bacterial product that may trigger this host response. The roles of exogenous PLC leading to the release, secretion and expression of MMPs by peripheral blood neutrophils (PMNs), cultured epithelial cells of human gingiva and porcine periodontal ligament were investigated. Also the activities of PLC in the diseased and healthy gingival sulcular fluid (crevicular fluid, GCF) and molecular forms of gelatin-ases present in dental plaque were investigated. MATERIALS AND METHODS GCF, salivary and dental plaque samples were analyzed for PLC and proteinase activities. The abilities of PLC to induce PMNs and oral epithelial cells to release and express their MMPs were examined by specific functional, immunological and molecular biology means. RESULTS: PMN-derived MMPs were found to predominate in periodontitis GCF and plaque, and PLC activities were higher in GCF of adult periodontitis patients than in healthy controls. Purified bacterial PLC (1 mU ml^-I) efficiently induced PMN degranulation. PLC also induced MMP expression in the cultured epithelial cells. The strongest response was seen in MMP-9 and less in MMP-2. The induction was dose-dependent in the range of 0.I-1.0 U ml^-1 PI-PLC, and quiescent cultures were more responsive than proliferating ones. PLC induction of MMPs was polar, with increased levels of MMP-9 in the apical region and increased MMP-2 levels secreted in the basal direction. Northern analysis showed a strong increase in mRNA levels of MMP-9 and a smaller increase for MMP-2 and MMP-I. In the second part of the study we investigated the molecular forms of the released MMPs during periodontitis. In bacterial plaque of periodontitis patients the MMP-9 were found to be converted into lower molecular weight forms. Isolated proteinase from Porphyromonas gingivalis (ATCC 33277) was able to convert human proMMPs to their active forms. CONCLUSION: Bacterial PLC may induce degranulation of PMN MMPs and increase MMP expression in oral epithelial cells. The released proteases can be converted into active form by the proteases of plaque bacteria. Thereby, the pathogenic oral bacteria may indirectly participate in the destruction of periodontal tissues.     

Waist Circumference Distribution of Chinese School-age Children and Adolescents

Background Waist circumference （WC）, a proxy measure of central body fat, is a better predictor than overall body fat for cardiovascular risk factors in both adults and children. WC cutoffs have been established in many countries, but the national WC reference has not been developed in China. Objective To study the distribution of WC in a representative group of Chinese children for establishing Chinese WC cutoff points. Methods Cross-sectional data obtained from 15 mainland provinces and Hong Kong were collected. There were 160 225 children and adolescents aged 7-18 years old in total. The subjects were divided into five regional groups namely costal city, other city, noah rural, south rural, and Hong Kong, for analyzing the distribution of WC. Results A large variation in WC distribution was found among the five groups for both sexes. Coastal city group had the highest P85 WC values consistently from the early school ages to 18-year-old compared with other groups. In contrast, south rural group had P85 values consistently lagged behind not only the city groups but also the north rural group. Hong Kong group had a high P85 WC at early ages, but because of the smaller increments of WC during adolescence, the P85 curve was gradually exceeded by the north rural groups. Catch-up trend was found in the two rural groups since the peak of puberty. These disparities were caused by not only socioeconomic and urban-rural factors but also north-south differences. Because of the regional variation of WC, a ＂gradient＂ prevalence of central obesity was prospected among these groups. Comparisons of WC distributions between the Chinese and the U.S.A or Netherlands demonstrated the necessary of setting up China＇s own WC cutoffs. Sex and age-specific percentiles were obtained and smoothed by using LMS method. Conclusion The data obtained from this study could be used to develop national WC cutoff points for Chinese children and adolescents.     

Effect of pulley integrity on excursions and work of flexion in healing flexor tendons

Effect of pulley integrity on excursions and work of flexion in healing flexor tendons@Wang YH @Gu YT @Chen F     

培养心肌细胞牵张刺激装置的建立及应用

1　方法　牵张刺激装置的制作如模式图 1.制作实验模型采用材料为有机玻璃板、2 4孔培养板、硅胶膜 (厚度 0 .2 2 μｍ) .硅胶膜从平面圆形变为球形时 ,面积扩大的百分比 =(Ｓ球 -Ｓ园 ) /Ｓ园 ,其中Ｓ球 =ＡＤ2 ,Ｓ园 =ｒ2 ,而ＡＤ2 =ｈ2 +ｒ2 ,其中ｒ为孔的半径 ,ｈ为膜升高的高度图 2 .通过控制ｈ的大小 ,可控制膜被牵拉的强度 .本实验采用使膜面积扩大 2 0 %的强度 ,故ｈ =4ｍｍ[1] .参照Ｋａｓｓｉｒｉ等[2 ,3 ] 方法进行心肌细胞的分离培养 .生长有贴壁心肌细胞的 2 4孔板被固定于牵张装置 ,缓慢充气使硅胶膜向上凸起 4ｍｍ ,分别维持…     

Effects of interruptions of external beam radiation therapy on outcomes in patients with prostate cancer

Introduction

To evaluate if interruptions of external beam radiation therapy impact outcomes in men with localized prostate cancer (PCa).

Methods

We included men with localized PCa treated with three‐dimensional conformal radiotherapy (3D‐CRT) or intensity‐modulated radiation therapy (IMRT) of escalated dose (≥74 Gy in 1.8 or 2 Gy fractions) between 1992 and 2013 at an NCI‐designated cancer centre. Men receiving androgen deprivation therapy were excluded. The non‐treatment day ratio (NTDR) was defined as the number of non‐treatment days divided by the total elapsed days of therapy. NTDR was analysed for each National Comprehensive Cancer Network (NCCN) risk group.

Results

There were 1728 men included (839 low‐risk, 776 intermediate‐risk and 113 high‐risk), with a median follow up of 53.5 months (range 12–185.8). The median NTDR was 31% (range 23–71%), translating to approximately 2 breaks (each break represents a missed treatment that will be made up) for 8 weeks of RT with 5 treatments per week. The 75 percentile of NTDR was 33%, translating to approximately 4 breaks, which was used as the cutoff for analysis. There were no significant differences in freedom from biochemical failure, freedom from distant metastasis, cancer specific survival, or overall survival for men with NTDR ≥33% compared to NTDR<33% for each risk group. Multivariable analyses including NTDR, age, race, Gleason score, T stage, and PSA were performed using the proportional hazards regression procedure. NTDR≥33% was not significantly associated with increased hazard ratio for outcomes in each risk group compared to NTDR<33%.

Conclusion

Unintentional treatment breaks during dose escalated external beam radiation therapy for PCa did not cause a significant difference in outcomes, although duration of follow up limits the strength of this conclusion.     

Serum hepatitis B surface antigen correlates with fibrosis and necroinflammation: A multicentre perspective in China

The kinetics of serum hepatitis B surface antigen (HBsAg) during the natural history of hepatitis B virus (HBV) infection has been studied, but the factors affecting them remain unclear. We aimed to investigate the factors affecting HBsAg titres, using data from multicentre, large‐sized clinical trials in China. The baseline data of 1795 patients in 3 multicentre trials were studied, and the patients were classified into 3 groups: hepatitis B early antigen (HBeAg)‐positive chronic HBV infection (n = 588), HBeAg‐positive chronic hepatitis B (n = 596), and HBeAg‐negative chronic hepatitis B (n = 611). HBsAg titres in the different phases were compared, and multiple linear progression analyses were performed to investigate the implicated factors. HBsAg titres varied significantly in different phases (P = .000), with the highest (4.60 log10 IU/mL [10%‐90% confidence interval: 3.52 log10 IU/mL‐4.99 log10 IU/mL]) in patients with HBeAg‐positive chronic HBV infection. In all phases, age and HBV DNA were correlated with serum HBsAg level. In HBeAg‐positive chronic hepatitis B patients, a negative correlation between HBsAg titres and fibrosis stage was observed. Alanine amonitransferase or necroinflammatory activity was also correlated with HBsAg titres in HBeAg‐negative chronic hepatitis B patients. In conclusion, decreased HBsAg titres may be associated with advancing fibrosis in HBeAg‐positive chronic hepatitis B patients or increased necroinflammation in those with HBeAg‐negative chronic hepatitis B. Our findings may help clinicians better understand the kinetics of HBsAg and provide useful insights into the management of this disease.