Nonsteroidal Anti-Inflammatory Drugs for Wounds: Pain Relief or Excessive Scar Formation?

The inflammatory process has direct effects on normal and abnormal wound healing. Hypertrophic scar formation is an aberrant form of wound healing and is an indication of an exaggerated function of fibroblasts and excess accumulation of extracellular matrix during wound healing. Two cytokines—transforming growth factor-β (TGF-β) and prostaglandin E2 (PGE2)—are lipid mediators of inflammation involving wound healing. Overproduction of TGF-β and suppression of PGE2 are found in excessive wound scarring compared with normal wound healing. Nonsteroidal anti-inflammatory drugs (NSAIDs) or their selective cyclooxygenase-2 (COX-2) inhibitors are frequently used as a pain-killer. However, both NSAIDs and COX-2 inhibitors inhibit PGE2 production, which might exacerbate excessive scar formation, especially when used during the later proliferative phase. Therefore, a balance between cytokines and medication in the pathogenesis of wound healing is needed. This report is a literature review pertaining to wound healing and is focused on TGF-β and PGE2

Emergence of Ceftriaxone-Resistant Salmonella Isolates and Rapid Spread of Plasmid-Encoded CMY-2–Like Cephalosporinase, Taiwan

Of 384 Salmonella isolates collected from 1997 to 2000 in a university hospital in Taiwan, six ceftriaxone-resistant isolates of Salmonella enterica serovar Typhimurium were found in two patients in 2000. The resistance determinants were on conjugative plasmids that encoded a CMY-2–like cephalosporinase. During the study period, the proportion of CMY-2–like enzyme producers among Escherichia coli increased rapidly from 0.2% in early 1999 to >4.0% in late 2000. Klebsiella pneumoniae isolates producing a CMY-2–like β-lactamase did not emerge until 2000. The presence of blaCMY-containing plasmids with an identical restriction pattern from Salmonella, E. coli, and K. pneumoniae isolates was found, which suggests interspecies spread and horizontal transfer of the resistance determinant. Various nosocomial and community-acquired infections were associated with the CMY-2–like enzyme producers. Our study suggests that the spread of plasmid-mediated CMY-2–like β-lactamases is an emerging threat to hospitalized patients and the public in Taiwan

The investigation of Mitogen-Activated Protein kinase Phosphatase-1 as a potential pharmacological target in non-small cell lung carcinomas, assisted by non-invasive molecular imaging

<p>Abstract</p> <p>Background</p> <p>Invasiveness and metastasis are the most common characteristics of non small cell lung cancer (NSCLC) and causes of tumour-related morbidity and mortality. Mitogen-activated protein kinases (MAPKs) signalling pathways have been shown to play critical roles in tumorigenesis. However, the precise pathological role(s) of mitogen-activated protein kinase phosphatase-1 (MKP-1) in different cancers has been controversial such that the up-regulation of MKP-1 in different cancers does not always correlate to a better prognosis. In this study, we showed that the induction of MKP-1 lead to a significant retardation of proliferation and metastasis in NSCLC cells. We also established that rosiglitazone (a PPARγ agonist) elevated MKP-1 expression level in NSCLC cells and inhibited tumour metastasis.</p> <p/> <p>Methods</p> <p>Both wildtype and dominant negative forms of MKP-1 were constitutively expressed in NSCLC cell line H441GL. The migration and invasion abilities of these cells were examined in vitro. MKP-1 modulating agents such as rosiglitazone and triptolide were used to demonstrate MKP-1's role in tumorigenesis. Bioluminescent imaging was utilized to study tumorigenesis of MKP-1 over-expressing H441GL cells and anti-metastatic effect of rosiglitazone.</p> <p>Results</p> <p>Over-expression of MKP-1 reduced NSCLC cell proliferation rate as well as cell invasive and migratory abilities, evident by the reduced expression levels of MMP-2 and CXCR4. Mice inoculated with MKP-1 over-expressing H441 cells did not develop NSCLC while their control wildtype H441 inoculated littermates developed NSCLC and bone metastasis. Pharmacologically, rosiglitazone, a peroxisome proliferator activated receptor-γ (PPARγ) agonist appeared to induce MKP-1 expression while reduce MMP-2 and CXCR4 expression. H441GL-inoculated mice receiving daily oral rosiglitazone treatment demonstrated a significant inhibition of bone metastasis when compared to mice receiving sham treatment. We found that rosiglitazone treatment impeded the ability of cell migration and invasion <it>in vitro</it>. Cells pre-treated with triptolide (a MKP-1 inhibitor), reversed rosiglitazone-mediated cell invasion and migration.</p> <p>Conclusion</p> <p>The induction of MKP-1 could significantly suppress the proliferative and metastatic abilities of NSCLC both in vitro and in vivo. Therefore, MKP-1 could be considered as a potential therapeutic target in NSCLC therapy and PPARγ agonists could be explored for combined chemotherapy.</p

Instability Index Derived from a Landslide Inventory for Watershed Stability Assessment and Mapping

Watersheds represent natural units of social&ndash;ecological systems and affect crop productivity. Extreme weather events accelerate the natural erosion process by triggering more landslides in watersheds. To achieve the land degradation neutrality set up by the UN&rsquo;s Sustainable Development Goals, it is necessary to assess and map spatiotemporal landslides in watersheds. This paper proposes an innovative approach to calculating the instability index by preparing an annual landslide inventory, determining the optimum sub-watershed, compensating for shadow effects on the time series of the landslide area ratio, and classifying the standard deviations to different levels of instability. Taking the Qingquan watershed as an example, the instability index calculated for 22 sub-watersheds makes it possible to identify hot spots that are prone to collapse. This new index can also be used to evaluate the effectiveness of watershed management before and after completion of a specific engineering project, as well as to update the latest upriver situation to evaluate current management practices and develop strategies for future planning. Based on this new approach, the Soil and Water Conservation Bureau of Taiwan assesses the stability of 28 watersheds, and the results are made available on the Big Geospatial Information System

Taiwanese Dermatological Association consensus for the definition, classification, diagnosis, and management of urticaria

This report describes the 2014 consensus of the Taiwanese Dermatological Association regarding the definition, classification, diagnosis, and management of urticaria. This consensus is distributed to practices throughout Taiwan to provide recommendations for diagnostic and therapeutic approaches for common subtypes of urticaria, in order to improve the quality of life of urticaria patients. The consensus, thus, serves as an important reference for dermatologists throughout Taiwan. Methods: All the consensus contents were voted on by the participating dermatologists, with approval by no less than 75% being required for inclusion. The consensus provides a comprehensive overview of urticaria, including recent advances in identifying its causes and the processes by which it develops. Results: All the consensus meeting attendees agreed to a definition of urticaria, which states that it is characterized by the sudden appearance of wheals (also known as hives), angioedema, or both. Most of the experts (16 out of 19, or 84.2%) agreed that chronic urticaria is defined as the sudden occurrence of wheals and/or angioedema for a period of ≥ 6 weeks. In addition, the consensus attendees also approved the Urticaria Activity Score system or the Urticaria Activity Score for 7 days system as the recommended method for assessing disease activity in spontaneous urticaria. Conclusion: It was also determined that the treatment goal for patients with any form of urticaria should be complete cessation of suffering from all urticaria symptoms. The recommended treatment algorithms for chronic spontaneous urticaria and acute urticaria were finally proposed and approved by 100% (19/19) and 84.2% (16/19) of the consensus attendees, respectively

Anti-adhesive effect of hyaluronate in a rabbit laminectomy model

Background: Postlaminectomy dural adhesion is a common cause of recurrent symptoms. Hyaluronic acid-based gel has been reported to reduce the incidence of postoperative adhesion in the peritoneal cavity; however, its effect on preventing postoperative scar formation at laminectomy sites is not yet known. The purpose of this study was to evaluate the anti-adhesive effect of hyaluronic acid-based gelatin after laminectomy, using a rabbit model. Methods: Twelve adult New Zealand rabbits underwent two-level lumbar laminectomy, and were randomly assigned to one of two groups of six rabbits each. The treatment group received hyaluronic acid-based gelatin treatment and the control group was untreated. Rabbits were sacrificed 8 weeks after treatment. Peel-off testing and histological analysis were performed to assess the tenacity and the extent of adhesion formation. Results: No significant difference was observed in the neurologic performance between the two groups. The tenacity in the treatment group was significantly reduced compared to that of the control group (3.17 ± 0.75 vs. 4.33 ± 0.52, respectively; p = 0.016). Histological analysis showed significantly less scar tissue formation in the treatment group, with a larger subarachnoid space and greater distance between the dura and scar tissues. The amount of fibroblast cells also was significantly smaller in the treatment group than in the control group (3078 ± 313.68 vs. 3742 ± 455.65, respectively; p = 0.042). Conclusions: No serious adverse events were reported, and no difference was found in the incidence of complications between the treatment and control groups. The findings suggested that hyaluronic acid-based gelatin may be effective for preventing postlaminectomy dural adhesion in rabbits

PRMT1 Confers Resistance to Olaparib via Modulating MYC Signaling in Triple-Negative Breast Cancer

Treatment of triple-negative breast cancer (TNBC) remains an unmet clinical need owing to its lack of an efficient therapeutic target. The targeting of DNA repair by poly(ADP-ribose) polymerase (PARP) inhibitors has shown benefit for patients with the BRCA variation. However, sensitivities to the PARP inhibitors were reported regardless of BRCA status. Thus, exploring the underlying mechanisms is imperative. Herein, we identified that breast cancer cells with an elevated expression of protein arginine methyl transferase 1 (PRMT1) was associated with therapeutic sensitivity to the PARP inhibitor olaparib. The results of cell viability and colony formation assays indicated that the suppression of PRMT1 by small hairpin RNA or by the chemical inhibitor increased sensitivity to olaparib in human TNBC MDA-MB-231 and BT549 cells. Bioinformatic analysis revealed that PRMT1 expression was significantly associated with the MYC signature, and TNBC cells with higher PRMT1 and the MYC signature were associated with therapeutic sensitivity to olaparib. Mechanistic studies further demonstrated that knockdown of PRMT1 reduced the c-Myc protein level and downregulated the expression of MYC downstream targets, whereas overexpression of PRMT1 enhanced c-Myc protein expression. Moreover, the overexpression of PRMT1 promoted c-Myc protein stability, and the inhibition of PRMT1 downregulated c-Myc protein stability. Accordingly, the knockdown of PRMT1 inhibited homologous recombination gene expression. These data indicate that PRMT1 is instrumental in regulating DNA repair, at least in part, by modulating c-Myc signaling. Our data highlighted the PRMT1/c-Myc network as a potential therapeutic target in patients with TNBC

Factors influencing consumer adoption of USB-based Personal Health Records in Taiwan

Abstract Background Usually patients receive healthcare services from multiple hospitals, and consequently their healthcare data are dispersed over many facilities’ paper and electronic-based record systems. Therefore, many countries have encouraged the research on data interoperability, access, and patient authorization. This study is an important part of a national project to build an information exchange environment for cross-hospital digital medical records carried out by the Department of Health (DOH) of Taiwan in May 2008. The key objective of the core project is to set up a portable data exchange environment in order to enable people to maintain and own their essential health information. This study is aimed at exploring the factors influencing behavior and adoption of USB-based Personal Health Records (PHR) in Taiwan. Methods Quota sampling was used, and structured questionnaires were distributed to the outpatient department at ten medical centers which participated in the DOH project to establish the information exchange environment across hospitals. A total of 3000 questionnaires were distributed and 1549 responses were collected, out of those 1465 were valid, accumulating the response rate to 48.83%. Results 1025 out of 1465 respondents had expressed their willingness to apply for the USB-PHR. Detailed analysis of the data reflected that there was a remarkable difference in the “usage intention” between the PHR adopters and non-adopters (χ2 =182.4, p  Conclusions Higher Usage Intentions, Perceived Usefulness and Subjective Norm of patients were found to be the key factors influencing PHR adoption. Thus, we suggest that government and hospitals should promote the potential usefulness of PHR, and physicians should encourage patients' to adopt the PHR.</p