Investigation of the Antiasthmatic Properties of Ethanol Extract of Callophyllis japonica in Mice

Purpose: To determine whether an ethanol extract from Callophyllis japonica (C. japonica) could attenuate indices of airway inflammation in a murine model of ovalbumin (OVA)-induced asthma.Methods: The free radical scavenging activity of the C. japonica ethanol extracts (CJE) were investigated using an electron spin resonance (ESR) system. To make develop animal model of asthma, mice were sensitized and challenged with OVA.Results: CJE exhibited considerable scavenging activity of 71.08 ± 0.73, 79.11 ± 6.04%, 75.95 ± 7.01%, and 48.56 ± 5.96% of DPPH, alkyl, superoxide, and hydroxyl radicals, respectively. The successive intraperitoneal administration of CJE reduced the number of eosinophils in bronchoalveolar lavage (BAL) fluid, development of airway hyperresponsiveness (AHR), an increase in pulmonary Th2 cytokines, and allergen-specific immunoglobulin E (IgE).Conclusion: Administration of CJE markedly alleviates all indices of airway inflammation. This study provides evidence that CJE plays a critical role in the amelioration of the pathogenetic process of allergic asthma in mice.Keywords: Asthma, Phenolic contents, Free radical scavenging, Airway hyper-responsiveness, Cytokines, Immunoglobulin

Administration of ON 01210.Na after exposure to ionizing radiation protects bone marrow cells by attenuating DNA damage response

<p>Abstract</p> <p>Background</p> <p>Ionizing radiation-induced hematopoietic injury could occur either due to accidental exposure or due to diagnostic and therapeutic interventions. Currently there is no approved drug to mitigate radiation toxicity in hematopoietic cells. This study investigates the potential of ON 01210.Na, a chlorobenzylsulfone derivative, in ameliorating radiation-induced hematopoietic toxicity when administered after exposure to radiation. We also investigate the molecular mechanisms underlying this activity.</p> <p>Methods</p> <p>Male C3H/HeN mice (n = 5 mice per group; 6-8 weeks old) were exposed to a sub-lethal dose (5 Gy) of γ radiation using a ¹³⁷Cs source at a dose rate of 0.77 Gy/min. Two doses of ON 01210.Na (500 mg/kg body weight) were administered subcutaneously at 24 h and 36 h after radiation exposure. Mitigation of hematopoietic toxicity by ON 01210.Na was investigated by peripheral white blood cell (WBC) and platelet counts at 3, 7, 21, and 28 d after radiation exposure. Granulocyte macrophage colony forming unit (GM-CFU) assay was done using isolated bone marrow cells, and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) was performed on bone marrow sections at 7 d post-exposure. The DNA damage response pathway involving ataxia telangiectasia mutated (ATM) and p53 was investigated by Western blot in bone marrow cells at 7 d post-exposure.</p> <p>Results</p> <p>Compared to the vehicle, ON 01210.Na treated mice showed accelerated recovery of peripheral WBC and platelet counts. Post-irradiation treatment of mice with ON 01210.Na also resulted in higher GM-CFU counts. The mitigation effects were accompanied by attenuation of ATM-p53-dependent DNA damage response in the bone marrow cells of ON 01210.Na treated mice. Both phospho-ATM and phospho-p53 were significantly lower in the bone marrow cells of ON 01210.Na treated than in vehicle treated mice. Furthermore, the Bcl2:Bax ratio was higher in the drug treated mice than the vehicle treated groups.</p> <p>Conclusions</p> <p>ON 01210.Na treatment significantly mitigated the hematopoietic toxicity induced by a sub-lethal radiation dose. Mechanistically, attenuation of ATM-p53 mediated DNA damage response by ON 01210.Na is contributing to the mitigation of radiation-induced hematopoietic toxicity.</p

Backbone and side-chain 1H, 13C and 15N assignments of the ubiquitin-associated domain of human X-linked inhibitor of apoptosis protein

X-linked inhibitor of apoptosis protein (XIAP), a leading member of the family of inhibitor of apoptosis (IAP) proteins, is considered as the most potent and versatile inhibitor of caspases and apoptosis. It has been reported that XIAP is frequently overexpressed in cancer and its expression level is implicated in contributing to tumorigenesis, disease progression, chemoresistance and poor patient-survival. Therefore, XIAP is one of the leading targets in drug development for cancer therapy. Recently, based on bioinformatics study, a previously unrecognized but evolutionarily conserved ubiquitin-associated (UBA) domain in IAPs was identified. The UBA domain is found to be essential for the oncogenic potential of IAP, to maintain endothelial cell survival and to protect cells from TNF-α-induced apoptosis. Moreover, the UBA domain is required for XIAP to activate NF-κB. In the present study, we report the near complete resonance assignments of the UBA domain-containing region of human XIAP protein. Secondary structure prediction based on chemical shift index (CSI) analysis reveals that the protein is predominately α-helical, which is consistent with the structures of known UBA proteins

Traditional electrosurgery and a low thermal injury dissection device yield different outcomes following bilateral skin-sparing mastectomy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Although a skin- and nipple-sparing mastectomy technique offers distinct cosmetic and reconstructive advantages over traditional methods, partial skin flap and nipple necrosis remain a significant source of post-operative morbidity. Prior work has suggested that collateral thermal damage resulting from electrocautery use during skin flap development is a potential source of this complication. This report describes the case of a smoker with recurrent ductal carcinoma <it>in situ </it>(DCIS) who experienced significant unilateral skin necrosis following bilateral skin-sparing mastectomy while participating in a clinical trial examining mastectomy outcomes with two different surgical devices. This unexpected complication has implications for the choice of dissection devices in procedures requiring skin flap preservation.</p> <p>Case presentation</p> <p>The patient was a 61-year-old Caucasian woman who was a smoker with recurrent DCIS of her right breast. As part of the clinical trial, each breast was randomized to either the standard of care treatment group (a scalpel and a traditional electrosurgical device) or treatment with a novel, low thermal injury dissection device, allowing for a direct, internally controlled comparison of surgical outcomes. Post-operative follow-up at six days was unremarkable for both operative sites. At 16 days post-surgery, the patient presented with a significant wound necrosis in the mastectomy site randomized to the control study group. Following debridement and closure, this site progressively healed over 10 weeks. The contralateral mastectomy, randomized to the alternative device, healed normally.</p> <p>Conclusion</p> <p>We hypothesize that thermal damage to the subcutaneous microvasculature during flap dissection may have contributed to this complication and that the use of a low thermal injury dissection device may be advantageous in select patients undergoing skin- and nipple-sparing mastectomy.</p

Absence of influenza vaccination among high-risk older adults in Taiwan

<p>Abstract</p> <p>Background</p> <p>Older adults, who often have more than one chronic disease, are at greater risk of influenza and its complications. However, because they often see physicians for other more pressing complaints, their physicians, focusing on one condition, may forget to suggest preventive measures for other diseases such as influenza. This study investigates what major factors affect an older adult with more than one chronic condition missing a vaccination opportunity.</p> <p>Methods</p> <p>Retrospectively reviewing a nationally representative random sample of medical claims from Taiwan's National Health Insurance Research Database during the period 2004 - 2006, we first identified patients sixty-five years or older who had visited physicians. Each patient was assigned a proxy for health status, the Charlson Comorbidity Index (CCI) score. An older claimant was defined has having "absence of a vaccination" when he or she had visited a physician during an influenza season but did not receive an influenza vaccination. Multivariate logistic regression was performed to estimate how likely it would be for older adults with various CCI scores to miss a vaccination.</p> <p>Results</p> <p>Out of 200,000 randomly selected claims, 20,923 older adults were included in our final analysis. We found older adults with higher CCIs to be more likely to have an absence of vaccination (<it>p </it>< 0.01). Our multivariate logistic regression results revealed CCI to be the greatest predictor of absence of vaccination, after controlling for individual factors and medical setting. Older adults with CCI scores three or higher were nearly five times more likely to miss a vaccination than those with a CCI of zero [OR: 4.93 (95%CI, 4.47-5.42)]. Those with CCIs of one and two were 2.53 and 3.92 times more likely to miss vaccination than those with a CCI of zero [OR 2.53 (95%CI, 2.26-2.84) and OR 3.92 (95%CI, 3.51-4.38), respectively].</p> <p>Conclusions</p> <p>The greater the number of certain comorbid conditions, the greater the likelihood a flu vaccination will be missed. Physicians would be well advised to not let the presenting problems of older patients distract from other possible health problems that might also need attention, in this case influenza vaccinations.</p

A Forward Chemical Screen in Zebrafish Identifies a Retinoic Acid Derivative with Receptor Specificity

Background: Retinoids regulate key developmental pathways throughout life, and have potential uses for differentiation therapy. It should be possible to identify novel retinoids by coupling new chemical reactions with screens using the zebrafish embryonic model. Principal Findings: We synthesized novel retinoid analogues and derivatives by amide coupling, obtaining 80–92% yields. A small library of these compounds was screened for bioactivity in living zebrafish embryos. We found that several structurally related compounds significantly affect development. Distinct phenotypes are generated depending on time of exposure, and we characterize one compound (BT10) that produces specific cardiovascular defects when added 1 day post fertilization. When compared to retinoic acid (ATRA), BT10 shows similar but not identical changes in the expression pattern of embryonic genes that are known targets of the retinoid pathway. Reporter assays determined that BT10 interacts with all three RAR receptor sub-types, but has no activity for RXR receptors, at all concentrations tested. Conclusions: Our screen has identified a novel retinoid with specificity for retinoid receptors. This lead compound may be useful for manipulating components of retinoid signaling networks, and may be further derivatized for enhanced activity

Large Fragment Pre-S Deletion and High Viral Load Independently Predict Hepatitis B Relapse after Liver Transplantation

Hepatitis B virus (HBV) associated end-stage liver diseases are the leading causes of liver transplantation (LT) in Taiwan. Relapse of hepatitis B occurs after LT, raising the risk of graft failure and reducing patient survival. Although several oral antiviral agents have been approved for anti-HBV treatment, lamivudine (LAM) remained to be the most widely used preventive regimen in Taiwan. While several clinical predictors have been identified for hepatitis B relapse, the predictive roles of the histopathological characteristics in liver explants as well as the genotypic features of the viruses in pre-LT serum samples have not been assessed. Between September 2002 and August 2009, 150 consecutive hepatitis B surface antigen (HBsAg) positive patients undergoing LT were included for outcome analysis following assessment of the clinicopathological and virological factors prior to LT. Kaplan-Meier analyses discovered that pre-operative LAM treatment ≤3 months; membranous distribution and higher expression of tissue HBsAg in liver explants; preoperative viral load ≧106 copies/ml; and presence of large fragment (>100 base pairs) pre-S deletion (LFpreSDel) correlated significantly with hepatitis B relapse. Multivariate Cox regression analysis showed that the presence of LFpreSDel (P = 0.001) and viral load ≧106 copies/mL (P = 0.023) were independent predictors for hepatitis B relapse. In conclusion, besides high viral load, LFpreSDel mutation is an important independent predictor for hepatitis B relapse after LT. More aggressive preventive strategies should be applied for patients carrying these risk factors