A Salvia miltiorrhiza ethanol extract ameliorates tissue destruction caused by experimental periodontitis in rats.

BACKGROUND AND OBJECTIVE: Salvia miltiorrhiza Bunge (Labiatae), or Danshen, is a Chinese medicine used for treatment of cardiac diseases by improving blood circulation and inhibiting inflammatory responses. In this study, we aimed to determine whether an ethanol extract of S. miltiorrhiza can ameliorate tissue damage caused by periodontitis. MATERIAL AND METHODS: An ethanolic extract of S. miltiorrhiza roots was prepared, and its major constituents were determined by HPLC analysis, by comparison with known standards for the major bioactive components. The activity of the extract was evaluated in a rat model in which periodontitis was induced by ligation of a silk suture around the neck of molar teeth. The effects of the S. miltiorrhiza extract on periodontitis were assessed by dental radiography, micro-computed tomography and histology. RESULTS: The cemento-enamel junction-bone distances among the four different groups of rats were significantly different: the distance was shorter in groups treated with ligation + S. miltiorrhiza extract than in the group treated with ligation only, but was longer than in the nonligated group, regardless of the radiographic methods used. Histology and histometry also indicated a similar trend of less gingival inflammation and alveolar bone destruction in the histological sections from the S. miltiorrhiza extract groups than in those from the ligation group. CONCLUSION: Because the S. miltiorrhiza extract reduced tissue damage and bone loss caused by ligation-induced periodontitis in rats, we suggest that the S. miltiorrhiza extract might have an ameliorative effect on periodontal tissue destruction during the process of periodontitis.

Risk of cardiovascular adverse events from trastuzumab (Herceptin(®)) in elderly persons with breast cancer: a population-based study.

Randomized controlled trials have reported a 4-5 times increased risk of heart failure (HF) in breast cancer patients receiving trastuzumab (Herceptin (®) ) compared to patients who do not receive trastuzumab. However, data regarding the cardiac effects of trastuzumab on elderly patients treated in general practice remain very limited. Using the US surveillance, epidemiology, and end results (SEER)-Medicare database, we conducted a retrospective cohort study on the cardiac effects of trastuzumab use in all incident breast cancer patients diagnosed from 1998 to 2007 who were 66 years and older, had no prior recent claims for cardiomyopathy (CM) or HF, and were followed through 2009. We defined our outcome as the first CM/HF event after diagnosis. We performed Cox-proportional hazard models with propensity score adjustment to estimate CM/HF risk associated with trastuzumab use. A total of 6,829 out of 68,536 breast cancer patients (median age: 75) had an incident CM/HF event. Patients who received trastuzumab tended to be younger, non-white, diagnosed more recently, and had a stage IV diagnosis. Trastuzumab use was associated with an increased risk of CM/HF (HR = 2.08, 95 % CI 1.77-2.44, p < 0.001). The trastuzumab-associated CM/HF risk was stronger in patients who were younger (HR = 2.52 for 66-75 years and HR = 1.44 for 76 years and older, p < 0.001) and diagnosed in recent years (HR = 2.58 for 2006-2007 vs. 1.86 for 1998-2005, p = 0.01). The twofold risk of CM/HF associated with trastuzumab remained regardless of patients' diagnosis stage, presence of hypertension, cardiovascular comorbidities, or receipt of anthracyclines, taxanes, or radiation. Trastuzumab may double CM/HF risk among elderly breast cancer patients. Our findings reinforce the need to prevent and manage cardiac risk among elderly breast cancer patients receiving trastuzumab.

Bevacizumab use and risk of cardiovascular adverse events among elderly patients with colorectal cancer receiving chemotherapy: a population-based study.

BACKGROUND: Cardiovascular risk attributable to bevacizumab (Avastin(®), BEV) for treatment of metastatic colorectal cancer (CRC) remains unclear. We conducted a population-based cohort study to assess the safety of BEV use among patients aged ≥ 65. PATIENTS AND METHODS: We identified CRC patients diagnosed from 2005 to 2007 who received chemotherapy and were followed until 31 December 2009. Outcomes were 3-year risk of arterial thromboembolic events (ATEs), cardiomyopathy or congestive heart failure (CM/CHF), and cardiac death (CD) after chemotherapy initiation. We fitted Cox-proportional hazards (PHs) models with inverse-probability-of-treatment-weights and calculated hazard ratios (HRs) for the risk of adverse events. RESULTS: We identified 6803 CRC patients (median age: 73 years). Those with cardiac comorbidity were less likely to receive BEV (P < 0.0001). BEV is associated with an elevated risk of ATEs (HR = 1.82, 95% CI = 1.20-2.76, P < 0.001; rate difference: 3.5 additional cases/1000 person-years). We observed no association between BEV and CD or CM/CHF. CONCLUSIONS: In general practice, the cardiovascular risk of BEV in elderly CRC is modest. The observed ATEs risk is lower than reported in clinical trials, which may be due to careful patient selection. Our findings may facilitate clinical decision-making of BEV use in elderly patients.

Silica SBA-15 template assisted synthesis of ultrasmall and homogeneously sized copper nanoparticles.

The synthesis of spherical copper nanoparticles with extremely narrow size distribution by electroless copper deposition on mesoporous silica support is described. The materials were characterized by nitrogen sorption, transmission electron microscopy, x-ray diffractometry and Fourier transform infrared spectroscopy. The copper nanoparticles have a cubic crystalline structure and an average particle size of 5.5 +/- 0.8 nm. The copper nanoparticles are stable, without detectable oxidation or further agglomeration under ambient conditions even after months. These results demonstrate that electroless copper reduction can be conducted and constrained within the mesoporous silica framework, which pave the way for engineered mesoreactors.

Capsaicin may induce breast cancer cell death through apoptosis-inducing factor involving mitochondrial dysfunction.

The majority of breast cancer patients are resistant to chemotherapy or radiotherapy due to the down-regulation or lack of caspase-3 expression. Capsaicin was found to inhibit cancer cell growth in caspase-3-deficient human breast cancer cells. This study aimed to investigate the growth-inhibitive effect of capsaicin and its mechanisms in human breast cancer cell lines, MCF-7 and BT-20. The results showed that cell viability decreased in a dose-dependent manner in both the caspase-3-deficient and non-deficient cells through inducing cell apoptosis and arresting the cell cycle in the S phase. Capsaicin significantly decreased mitochondria membrane potential, induced the cleavage of PARP-1, and decreased procaspase-7 expression in both cells. Apoptosis-inducing factor (AIF) was distinctly released from mitochondria and translocated into the cytoplasm and nucleus in MCF-7 cells (52.9%), but not in BT-20 cells (2%) after treatment with 200 µM of capsaicin for 24 hours. Capsaicin inhibited breast cancer cell growth through inducing cell apoptosis and cell cycle arrest in the S phase. This apoptotic effect could be induced through the mitochondrial pathway, and PARP-1 subsequently cleaved by activation of caspase-7. The application of capsaicin in clinical therapy could be useful for breast cancer patients.

Pulmonary changes induced by trans,trans-2,4-decadienal, a component of cooking oil fumes.

Cooking oil fumes (COF) are known to be associated with respiratory diseases and risk of lung cancer. Involvement of trans,trans-2,4-decadienal (tt-DDE), a major component in COF, is suspected. Male CD-1(R) (ICR) mice were intratracheally instilled with either 8 or 24 mg.kg(-1) tt-DDE weekly for 8 weeks. Total numbers and types of cells in bronchoalveolar lavage fluid (BALF), as well as pathological changes, and inflammatory gene modulations in the lung tissues were assessed. We demonstrated that the number of alveolar macrophages in the BALF was significantly increased in tt-DDE-exposed animals. Histologically, there was a dose-correlated increase in epithelial hyperplasia and granulomatous nodules at the bronchioloalveolar junctions (BAJ). Although both Clara and alveolar type II cells were present in the BAJ lesion, only Clara cells were actively proliferative. However, only alveolar type II cells were found in the BAJ granulomatous nodules. Enhanced accumulation of phosphorylated signal transducer and activator of transcription 3 (pSTAT3), a known pro-carcinogenic factor, was also detected in many alveolar type II cells at the BAJ lesions. As both BAJ hyperplasia and enhanced pSTAT3 accumulation are known risk factors associated with increased lung adenocarcinoma development, these findings suggest that tt-DDE may pose a risk in lung carcinogenesis.

Enhancement of antitumor activity of gammaretrovirus carrying IL-12 gene through genetic modification of envelope targeting HER2 receptor: a promising strategy for bladder cancer therapy.

The objective of this study was to develop an HER2-targeted, envelope-modified Moloney murine leukemia virus (MoMLV)-based gammaretroviral vector carrying interleukin (IL)-12 gene for bladder cancer therapy. It displayed a chimeric envelope protein containing a single-chain variable fragment (scFv) antibody to the HER2 receptor and carried the mouse IL-12 gene. The fragment of anti-erbB2scFv was constructed into the proline-rich region of the viral envelope of the packaging vector lacking a transmembrane subunit of the carboxyl terminal region of surface subunit. As compared with envelope-unmodified gammaretroviruses, envelope-modified ones had extended viral tropism to human HER2-expressing bladder cancer cell lines, induced apoptosis, and affected cell cycle progression despite lower viral titers. Moreover, animal studies showed that envelope-modified gammaretroviruses carrying IL-12 gene exerted higher antitumor activity in terms of retarding tumor growth and prolonging the survival of tumor-bearing mice than unmodified ones, which were associated with enhanced tumor cell apoptosis as well as increased intratumoral levels of IL-12, interferon-gamma, IL-1beta, and tumor necrosis factor-alpha proteins. Therefore, the antitumor activity of gammaretroviruses carrying the IL-12 gene was enhanced through genetic modification of the envelope targeting HER2 receptor, which may be a promising strategy for bladder cancer therapy.

A notable accessory screening program for detection of cervical intraepithelial neoplasia.

OBJECTIVE: Papanicolaou (Pap) smear test is implemented to detect cervical intraepithelial neoplasia (CIN) in Taiwan. However, the utility of that has limitations. High-risk human papillomavirus (HR-HPV) is an important risk factor in development of cervical cancer. In this study, we estimate the utility of HR-HPV testing in the screening of CIN. METHODS: Firstly, 726 subjects were recruited and willing to prove cervical exfoliated epithelial cells for Pap smear screening and HR-HPV DNA testing. Subsequently, 205 of the eligible subjects with greater than or equal to CIN1 of Pap smear results were asked to perform histologic diagnosis that served as a gold standard for the estimation of the effects of both Pap smear and HR-HPV testing. RESULTS: The histology is significantly associated with HR-HPV infection, as well as significantly highly correlated with the individuals who have both Pap smear greater than or equal to CIN1 and positive HR-HPV infection but not significantly correlated with the individuals who only have Pap smear greater than or equal to CIN1 but without HR-HPV infection. CONCLUSIONS: Combinative surveillance of HR-HPV infection and Pap smear is a useful tool to detect and monitor precancerous lesions in the screening program. HR-HPV testing is a notable accessory screening program for detection of CIN in Taiwanese women.

Identification of a Potyvirus Causing Latent Infection in Calla Lilies.

A new potyvirus designated as Calla lily latent virus (CLLV) was isolated from apparently healthy calla lilies (Zantedeschia spp.) collected from nurseries in Taichung County, Taiwan. Different from most calla lily-infecting potyviruses, CLLV infects Chenopodium quinoa and develops local lesions on inoculated leaves (3). Typical potyvirus particles approximately 780 nm long were detected from CLLV-induced C. quinoa local lesions. CLLV was transmitted readily to and established in C. quinoa. Attempts to establish CLLV infection in calla lilies from extracts of C. quinoa lesions were not successful. The virus was transmitted from infected to healthy calla lilies with difficulty. A 1.3-kb cDNA product was amplified by reverse transcription-polymerase chain reaction (RT-PCR) from CLLV-infected calla lilies and C. quinoa using potyvirus degenerate primers (2). The PCR product was cloned and sequenced. It was found to consist of 1,339 nucleotides (nt) (GenBank Accession No. AF469171) corresponding to the genome organization of the 3'terminal region of potyviruses. The deduced amino acid sequence contains 362 residues encoding the 3'terminal region of the nuclear inclusion b gene (80 residues) and the complete coat protein (CP) gene (282 residues). A 253-nt noncoding region (NCR) was found at the 3'terminal region of the cDNA. By comparing with known sequences of potyviruses, CLLV was identified as a new species of Potyvirus based on the uniqueness in the CP gene and 3' NCR. Soybean mosaic virus and Watermelon mosaic virus 2 are the potyviruses most similar to CLLV, but they share only approximately 80% nucleotide identity with CLLV in the CP and NCR regions. Attempts to purify sufficient CLLV from C. quinoa for antiserum preparation were not successful. Alternatively, polyclonal antibodies were produced using E. coli-expressed CLLV CP (1). The antibodies were useful for detection of CLLV and its CP in calla lilies using enzyme-linked immunosorbent assay, sodium dodecyl sulfate-immunodiffusion, immuno-specific electron microscopy, and western blot. Field surveys showed that calla lily plants found positive for CLLV by serological methods always remained symptomless throughout the six-month growing season. Occasionally, CLLV was detected in symptomatic calla lilies, but these plants were consistently confirmed dually infected by other viruses (Dasheen mosaic virus and Konjak mosaic virus found most commonly). Infection of CLLV alone in calla lilies may not have a direct impact on the production and marketing of the crop. Synergism is not currently known when calla lilies are coinfected with other viruses. CLLV is spread by vegetative propagation through infected rhizomes or tubers. References: (1) C. C. Chen et al. Plant Dis. 87:901-905, 2003. (2) S. S. Pappu et al. Plant Dis. 82:1121-1125, 1998. (3) F. W. Zettler and R. D. Hartman. Pages 464-470 in: Virus and Virus-like Diseases of Bulb and Flower Crops. G. Loebenstein et al., eds. John Wiley and Sons Inc., UK, 1995.

Identification of Turnip mosaic virus Isolates Causing Yellow Stripe and Spot on Calla Lily.

Two virus cultures, RC4 and YC5, were isolated in Taiwan from calla lily (Zantedeschia spp.) cv. Black magic displaying yellow spot and stripe on leaves. Both isolates were mechanically transmitted to various hybrids of Zantedeschia and induced systemic symptoms similar to those observed on diseased Black magic. In addition to Zantedeschia spp., the two virus isolates also infected several cruciferous species and induced mosaic symptoms. Electron microscopy revealed the presence of flexuous virus particles about 750 nm in length. The two isolates were propagated in and purified from mustard plants and were used as immunogens for production of antisera in rabbits. In enzyme-linked immunosorbent assay and sodium dodecyl sulfate-immunodiffusion tests, both antisera reacted strongly with their homologous antigens and with antigens of two Turnip mosaic virus (TuMV) isolates from radish (TuMV-R) and lisianthus (TuMV-L), but not with 21 other different potyviruses tested. In reciprocal tests, antisera against TuMV-R and TuMV-L also reacted strongly with RC4 and YC5 antigens, indicating that these two calla lily isolates are serologically indistinguishable from other known TuMV strains. Cloning and sequence analyses confirmed that both isolates shared 95 to 99% of deduced amino acid sequence identities in the coat protein genes with those of various known TuMV strains. This investigation represents the first record of the natural infection of TuMV in calla lily.

Pollution by PCDDS and PCDFS in sediment from freshwater fish culture ponds near incineration sites for metal reclamation in Wan-Li, Taiwan, Republic of China.

Sediment samples from nine culture ponds for freshwater fish at and near waste incineration sites for metal reclamation in Wan-Li, southern Taiwan, Republic of China were analyzed for PCDDs and PCDFs by HRGC-HRMS. Four of nine samples were heavily polluted by PCDDs and PCDFs, indicating the latter to be dominant. The total TEQ concentrations of PCDDs and PCDFs in the four samples were in the range of 257 to 12200 pg/g dry weight. In addition, the levels corresponded to those of surface soil samples from the same waste combustion areas.