Secular trend for mortality from breast cancer and the association between diabetes and breast cancer in Taiwan between 1995 and 2006

Aims/hypothesis  Studies have identified an association between diabetes and breast cancer in postmenopausal women in Western countries. Such an association needs to be confirmed in an Asian population. The aim of this study was to evaluate the secular trend for breast cancer mortality in Taiwanese women in the general population and the mortality rate ratios between diabetic patients and the general population. Methods  Age-specific mortality rates for the general population, categorised into groups aged 25–54, 55–64, 65–74 and ≥75 years, were calculated for the years between 1995 and 2006 (inclusive) from vital statistics published by the Taiwanese government. Linear regression was used to test the trends. A total of 131,573 diabetic women aged ≥25 years from a national cohort recruited between 1995 and 1998 (inclusive) were followed prospectively for vital status, determined from the National Register of Deaths. Mortality rates and mortality rate ratios (mortality rate in diabetic women vs the average and highest mortality rates for the general population) were calculated. Results  A total of 14,230 women aged ≥25 years in the general population died of breast cancer between 1995 and 2006. A trend for an increase in the annual rate was observed for all age groups. A total of 482 diabetic women died of breast cancer, with a crude mortality rate of 45.7 per 100,000 person-years. Compared with the general population the relative risk of mortality for those with diabetes ranged from 1.37 (for the group aged 55–64 years) to 2.43 (for the group aged 25–54 years). Conclusions/interpretation  We identified a secular trend of an increase in the rate of breast cancer mortality in the Taiwanese general population. Our data suggest a higher risk of breast cancer mortality in diabetic patients in all age groups.     

过敏性紫癜合并支原体、EB病毒感染分析

目的：探讨HSP和支原体及EB病毒感染的关系。方法：对本院2008年1月～2009年12月收治的135例过敏性紫癜患儿进行肺炎支原体和EB病毒检测。结果：肺炎支原体阳性42例,占总例数的31.11%,EB病毒阳性43例,占总例数的31.85%,其中16例为二者混合感染,占总病例的11.85%。结论：过敏性紫癜病因复杂,但仍以感染为首要诱因。本院收治的135例HSP患儿,MP感染占31.11%,EBV感染的占31.85%,经过正规抗MP和EBV治疗后基本痊愈,提示MP和EBV感染和HSP有一定关系。     

Effects of decabrominated diphenyl ether (PBDE 209) on voltage‐gated sodium channels in primary cultured rat hippocampal neurons

Polybrominated diphenyl ethers (PBDEs) are widely used as flame‐retardant additives. But the application of PBDEs has been challenged due to their toxicity, especially neurotoxicity. In this study, we investigated the effects of decabrominated diphenyl ether (PBDE 209), the major PBDEs product, on voltage‐gated sodium channels (VGSCs) in primary cultured rat hippocampal neurons. Employing the whole‐cell patch‐clamp technique, we found that PBDE 209 could irreversibly decrease voltage‐gated sodium channel currents (I_Na) in a very low dose and in a concentration‐dependent manner. We had systematically explored the effects of PBDE 209 on I_Na and found that PBDE 209 could shift the activation and inactivation of I_Na toward hyperpolarizing direction, slow down the recovery from inactivation of I_Na, and decrease the fraction of activated sodium channels. These results suggested that PBDE 209 could affect VGSCs, which may lead to changes in electrical activities and contribute to neurotoxicological damages. We also showed that ascorbic acid, as an antioxidant, was able to mitigate the inhibitory effects of PBDE 209 on VGSCs, which suggested that PBDE 209 might inhibit I_Na through peroxidation. Our findings provide new insights into the mechanism for the neurological symptoms caused by PBDE 209. © 2009 Wiley Periodicals, Inc. Environ Toxicol 25: 400–408, 2010.     

SELPLG and SELP single-nucleotide polymorphisms in multiple sclerosis

P-Selectin (SELP) and P-selectin glycoprotein ligand-1 (SELPLG) constitute a receptor/ligand complex involved in the recruitment of activated lymphocytes, a critical event in the pathogenesis of multiple sclerosis (MS). In order to determine whether genetic variation in these pivotal molecules influences susceptibility to MS, we genotyped 214 Italian patients compared with 220 Italian controls for three single-nucleotide polymorphisms (SNPs): SELPLG Met62Ile, SELP C-2123G and SELP Thr715Pro. No significant differences in both SELP SNPs were found between patients and controls, whereas a decreased frequency of the Met62Ile SNP was found in patients versus controls in the Italian population (P = 0.025). To confirm these preliminary findings, the Met62Ile SNP was analysed in 938 UK trio families. This SNP did not show evidence for association with susceptibility to MS in the larger UK cohort. Therefore, none of the SNPs investigated is associated with MS, although this analysis does not conclusively exclude SELPLG and SELP as genetic risk factors for MS as much variation remains untested.     

Cardiac electrophysiology and tissue structure: bridging the scale gap with a joint measurement and modelling paradigm

Significant tissue structures exist in cardiac ventricular tissue that are of supracellular dimension. It is hypothesized that these tissue structures contribute to the discontinuous spread of electrical activation, may contribute to arrhymogenesis and also provide a substrate for effective cardioversion. However, the influences of these mesoscale tissue structures in intact ventricular tissue are difficult to understand solely on the basis of experimental measurement. Current measurement technology is able to record at both the macroscale tissue level and the microscale cellular or subcellular level, but to date it has not been possible to obtain large volume, direct measurements at the mesoscales. To bridge this scale gap in experimental measurements, we use tissue-specific structure and mathematical modelling. Our models have enabled us to consider key hypotheses regarding discontinuous activation. We also consider the future developments of our intact tissue experimental programme.     

Streptococcus pneumoniae protein vaccine candidates: properties, activities and animal studies

Streptococcus pneumoniae is a causative agent for community acquired pneumonia, bacteremia, acute otitis media, and meningitis. Recent emergence of multi-drug resistant clinical isolates prompts the need of effective vaccine for the prevention of disease. The licensed polysaccharide-based pneumococcal vaccines only elicit protective antibodies against the infection of serotypes that are included in the vaccine. To broaden the protection, the use of pneumococcal proteins will be a feasible and preferable alternative. This communication provides a review on the biochemical properties of these protein candidates, their immunization results in animal studies, and perspectives on the development of protein-based pneumococcal vaccine.     

Small peptide analogue of SDF-1alpha supports survival of cord blood CD34+ cells in synergy with other cytokines and enhances their ex vivo expansion and engraftment into nonobese diabetic/severe combined immunodeficient mice

The SDF-1/CXCR4 axis has been implicated in the chemotaxis, homing, mobilization, and expansion of hematopoietic stem and progenitor cells. We studied the effects of a SDF-1 peptide analogue CTCE-0214 on the survival of cord blood CD34+ cells in culture, expansion, and engraftment of expanded cells in the nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model. Our results demonstrated that CTCE-0214 synergized with thrombopoietin (TPO), stem cell factor (SCF), or flt-3 ligand (FL) on the survival of stem and progenitor cells in culture. Adding CTCE-0214 at a low concentration (0.01 ng/ml) for 4 days together with TPO, SCF, and FL significantly enhanced ex vivo expansion of CD34+ cells to subsets of primitive (CD34+CD38- cells, colony-forming unit-mixed [CFU-GEMMs]), erythroid (CFU-Es), myeloid (CFU-GMs), and megakaryocytic (CD61+CD41+ cells, CFU-MKs) progenitors, as well as their multilineage engraftment in NOD/SCID mice. Interestingly, the short exposure of expanded cells to CTCE-0214 (100 and 500 ng/ml) for 4 hours did not increase the quantity of progenitor cells but enhanced their engraftment capacity. The proportion of CD34+ cells expressing surface CXCR4 was decreased, but the overall number of this population increased upon expansion. The small peptide analogue of SDF-1 could be developed for ex vivo expansion and improving engraftment of cord blood transplantation.     

A two-year randomized clinical trial of chlorhexidine varnish on dental caries in Chinese preschool children

The objective of this study was to assess the effect of six-monthly professional applications of chlorhexidine varnish on the prevention of dental caries in primary molars in Chinese preschool children. In a double-blinded, randomized, placebo-controlled clinical trial, 334 children aged 4-5 years were randomly divided into two groups. Children in the test group received six-monthly applications of a 40% chlorhexidine varnish, and the control children received a placebo varnish. Caries status of the children was assessed by two calibrated examiners at baseline and after 24 months, according to criteria recommended by the World Health Organization. The two-year mean caries increments in the test and the control group children were 1.0 and 1.6 decayed, missing, or filled molar surfaces (dmfs-molar), respectively, a 37.3% reduction (t test, p = 0.036). No side-effects were found. It was concluded that six-monthly applications of chlorhexidine varnish were effective in reducing the incidence of dental caries in primary molars.     

The cationic host defense peptide rCRAMP promotes gastric ulcer healing in rats

Cathelicidin, a cationic host defense peptide, has been shown to promote cutaneous wound repair and reaches high levels in the gastric mucosa during infection and inflammation. Therefore, we investigated whether this peptide contributes to gastric ulcer healing in rats. Ulcer induction increased the expression of rat cathelicidin rCRAMP in the gastric mucosa. Further increase in expression of rCRAMP by local injection of rCRAMP-encoding plasmid promoted ulcer healing by enhancing cell proliferation and angiogenesis. rCRAMP directly stimulated proliferation of cultured rat gastric epithelial cells (RGM-1), which was abolished by inhibitors of matrix metalloproteinase (MMP), epidermal growth factor receptors (EGFR) tyrosine kinase, or mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase. rCRAMP also increased EGFR and ERK1/2 phosphorylation via an MMP-dependent mechanism. Knockdown of transforming growth factor alpha (TGFalpha), which is a ligand of EGFR, by small interfering RNA completely nullified the mitogenic signals evoked by rCRAMP in RGM-1 cells. These findings suggest that rCRAMP exhibits prohealing activity in stomachs through TGFalpha-dependent transactivation of EGFR and its related signaling pathway to induce proliferation of gastric epithelial cells.