Stephania tetrandra prevents and regresses liver fibrosis induced by carbon tetrachloride in rats

Background and Aim:  There is currently no safe and effective treatment for liver fibrosis. We have previously shown that Stephania tetrandra ( ST ) and Salvia miltiorrhiza ( SM ) suppress cell proliferation and enhance apoptosis of hepatic stellate cell (HSC) in vitro . In this study, we aimed to investigate the anti-fibrotic effect of these two herbs in vivo .
Methods:  Liver fibrosis was induced by carbon tetrachloride (CCl₄) injection in rats for 5 weeks. SM , ST or SM  +  ST was gavaged on day 1 of CCl₄ administration to study the preventive effects of herbs on hepatic fibrosis. In a separate study designed to assess possible fibrosis regression, rats were randomly allocated to be treated with SM, ST or SM  +  ST when fibrosis was established. Liver injury and collagen content were assessed. HSC activation and apoptosis were determined.
Results:  As compared with the CCL₄-only rats, serum ALT was significantly lower in CCl₄-treated rats that received either SM ( P  < 0.01) or ST ( P  < 0.01). Administration of ST significantly prevented ( P  < 0.01) or reversed the hepatic fibrosis ( P  < 0.01) induced by CCL₄. Moreover, rats treated with ST had reduced protein expression of α-SMA both in prevention ( P  < 0.05) and in regression ( P  < 0.01) experiments. The double-color staining of α-SMA and TUNEL showed that ST increased HSC apoptosis. However, co-treatment of SM  +  ST did not increase the antifibrotic effect of ST .
Conclusions:  Stephania tetrandra safely and effectively prevents and reverses hepatic fibrosis through activating HSC apoptosis in rats.     

Practical vaccination guidelines for children with cancer

The paediatrician or family physician usually provides primary care for children diagnosed with cancer. Immunizations are an important facet of this care, but guidelines for the immunization of these immunocom-promised children are difficult to locate and cumbersome to follow. The authors have developed immunization guidelines for children receiving chemotherapy for cancer that will hopefully facilitate the care of this group of children. Before initiating any immunizations in this group of children, communication with a cancer specialist is recommended. There is little evidence-based literature to support immunization guidelines in immunocompromised hosts; thus, the recommendations presented are derived from the available literature, existing guidelines and expert opinion.     

WNT5A exhibits tumor-suppressive activity through antagonizing the Wnt/beta-catenin signaling, and is frequently methylated in colorectal cancer.

PURPOSE: Aberrant activation of the Wnt/beta-catenin signaling pathway is associated with multiple tumors including colorectal cancer (CRC). WNT5A is a member of the nontransforming Wnt protein family, whose role in tumorigenesis is still ambiguous. We investigated its epigenetic alteration in CRCs. EXPERIMENTAL DESIGN: We examined its expression and methylation in normal colon, CRC cell lines, and tumors. We also evaluated its tumor-suppressive function and its modulation to Wnt signaling in CRC cells. RESULTS: WNT5A is silenced in most CRC cell lines due to promoter methylation, but is expressed in most normal tissues including the colon, and is unmethylated in normal colon epithelial cells. WNT5A expression could be reactivated by pharmacologic or genetic demethylation, indicating that methylation directly mediates its silencing. WNT5A methylation was frequently detected in CRC tumors (14 of 29, 48%), but only occasionally in paired normal colon tissues (2 of 15, 13%; P = 0.025). Ectopic expression of WNT5A, but not its nonfunctional short-isoform with the WNT domain deleted, in silenced CRC cells resulted in substantial inhibition of tumor cell clonogenicity, which is associated with down-regulated intracellular beta-catenin protein level and concomitant decrease in beta-catenin activity. CONCLUSIONS: WNT5A is frequently inactivated in CRC by tumor-specific methylation, and thus, is a potential biomarker. WNT5A could act as a tumor suppressor for CRC by antagonizing the Wnt/beta-catenin signaling.     

Expression of a peroxisome proliferator-activated receptor gamma 1 splice variant that was identified in human lung cancers suppresses cell death induced by cisplatin and oxidative stress.

PURPOSE: The activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) has been implicated in the inhibition of tumor progression in lung cancers through the induction of differentiation and apoptosis. Recently, we identified a novel splice variant of human PPAR gamma1 (hPPAR gamma1) that exhibits dominant-negative activity in human tumor-derived cell lines. This study aimed to examine the expression and pathophysiologic roles of a truncated splice variant of hPPAR gamma1 (hPPAR gamma1(tr)) in primary human lung cancer tissues. EXPERIMENTAL DESIGN: The expression and localization of hPPAR gamma1(tr) was surveyed in human primary lung cancer tissues using immunohistochemistry and Western blot analysis. Using transfectants stably expressing wild-type hPPAR gamma1 (hPPAR gamma1(wt)) and hPPAR gamma1(tr), we also analyzed the pathophysiologic roles of hPPAR gamma1(tr). RESULTS: We showed that PPAR gamma is expressed predominantly in the nucleus of nontumorous tissues, whereas it is present in both the nucleus and the cytoplasm of tumorous tissues in squamous cell carcinoma (SCC) of the lung. Western blot analysis confirmed the presence of PPAR gamma1(tr) in primary lung SCC tissue but not in nontumorous tissue. Expression of PPAR gamma1(tr) in Chinese hamster ovary cells attenuated their susceptibility to cell death induced by oxidative stress or cisplatin, whereas their susceptibility was completely recovered by down-regulation of PPAR gamma1(tr) with small interfering RNA. CONCLUSIONS: hPPAR gamma1(tr) is expressed strongly in tumorous tissues of primary human lung SCC and its overexpression renders transfected cells more resistant to chemotherapeutic drug- and chemical-induced cell death. These data suggest that the decreased drug sensitivity of PPAR gamma1(tr)-expressing cells may be associated with increased tumor aggressiveness and poor clinical prognosis of patients.     

Changes of aqueous vascular endothelial growth factor and interleukin‐6 after intravitreal triamcinolone for branch retinal vein occlusion

Background: To investigate sequential changes of aqueous vascular endothelial growth factor (VEGF) and interleukin (IL)‐6 in macular oedema secondary to branch retinal vein occlusion after single intravitreal injection of triamcinolone acetonide (IVTA). Methods: We recruited 10 healthy controls and 30 patients at Chonnam National University Hospital, Gwangju, Korea. Aqueous and plasma levels of VEGF and IL‐6 were measured by enzyme‐linked immunosorbent assay at the time of IVTA and 3 months later. Non‐response to IVTA was defined as showing persistent macular oedema based on a reduction of central macular thickness by less than 20% from baseline measurements by optical coherence tomography and vision improvement by less than 0.3 logMAR. Fluorescein angiography was performed 6 months after IVTA. We compared aqueous levels of VEGF and IL‐6 between responders and non‐responders. Results: The aqueous levels of VEGF and IL‐6 were significantly higher in 12 non‐responders than in 18 responders at baseline measurements (511 ± 245 pg/mL vs. 230 ± 108 pg/mL, P < 0.001; 38 ± 31 pg/mL vs. 16 ± 13 pg/mL, P < 0.001, respectively). Aqueous levels of VEGF were still higher in non‐responders (312 ± 64 pg/mL) 3 months after IVTA, and aqueous levels of VEGF in responders returned to normal (86 ± 21 pg/mL, P < 0.001). Aqueous levels of IL‐6 normalized in all patients 3 months after IVTA. Fluorescein angiography revealed that non‐responders showed higher frequencies of macular ischaemia and ischaemic branch retinal vein occlusion. Conclusions: IL‐6‐independent VEGF secretion may contribute to persistent macular oedema associated with ischaemic BRVO after IVTA.     

Evaluation of a vectored equine herpesvirus type 1 (EHV-1) vaccine expressing H3 haemagglutinin in the protection of dogs against canine influenza.

In 2004, canine influenza virus (CIV) was identified as a respiratory pathogen of dogs for the first time and found to be closely related to H3N8 equine influenza virus (EIV). We generated a recombinant vectored vaccine that expresses H3 of a recent isolate of EIV using equine herpesvirus type 1 (EHV-1) as the delivery vehicle. This EHV-1 vectored vaccine exhibited robust and stable EIV H3 expression and induced a strong influenza virus-specific response in both mice and dogs upon intranasal or subcutaneous administration. Furthermore, upon challenge with the recent CIV isolate A/canine/PA/10915-07, protection of vaccinated dogs could be demonstrated by a significant reduction in clinical sings, and, more importantly, by a significant reduction in virus shedding. We concluded that the EHV-1/H3 recombinant vector can be a valuable alternative for protection of dogs against clinical disease induced by CIV and can significantly reduce virus spread.     

Epidemiological investigation of a measles outbreak in a preschool in Incheon, Korea, 2006]

OBJECTIVES: This study describes a plan that was designed to prevent a measles outbreak that showed a changed outbreak pattern. This study is based on the epidemiological investigation of a measles outbreak in a preschool in Incheon, Korea, 2006. METHODS: The subjects were 152 students at a preschool where a measles outbreak occurred. A questionnaire survey was conducted and serological testing for measles specific IgM was preformed. RESULTS: Of the fifteen confirmed, identified cases, eleven patients had been vaccinated with one dose, one patient had received two doses and three patients were unvaccinated. The three unvaccinated cases consisted of one 5-year-old child, one 3-year-old child and one 16-month-old infant. For the cases with one dose of the vaccination, there were 11 cases, which consisted of six 5-year-old children, two 4-year-old children, two 3-year-old children and one 2-year-old child. The case with two doses of the vaccination was one 4-year-old child. The attack rate of measles was 100% in the 0-dose group, 11.2% in the 1-dose group and 2.0% in the 2-dose group. The vaccine's efficacy was 88.8% in the 1-dose group and 98.0% in the 2-dose group. The vaccine effectiveness for the 2-dose group was higher than that of the 1-dose group. CONCLUSIONS: High coverage with a 2-dose vaccination should be maintained, and the vaccination should be given at the suitable time to prevent a measles outbreak with a changed outbreak pattern.