Inhibition of the tyrosine phosphatase SHP-2 suppresses angiogenesis in vitro and in vivo

Endothelial cell survival is indispensable to maintain endothelial integrity and initiate new vessel formation. We investigated the role of SHP-2 in endothelial cell survival and angiogenesis in vitro as well as in vivo. SHP-2 function in cultured human umbilical vein and human dermal microvascular endothelial cells was inhibited by either silencing the protein expression with antisense-oligodesoxynucleotides or treatment with a pharmacological inhibitor (PtpI IV). SHP-2 inhibition impaired capillary-like structure formation (p < 0.01; n = 8) in vitro as well as new vessel growth ex vivo (p < 0.05; n = 10) and in vivo in the chicken chorioallantoic membrane (p < 0.01, n = 4). Additionally, SHP-2 knock-down abrogated fibroblast growth factor 2 (FGF-2)-dependent endothelial proliferation measured by MTT reduction ( p ! 0.01; n = 12). The inhibitory effect of SHP-2 knock-down on vessel growth was mediated by increased endothelial apoptosis ( annexin V staining, p ! 0.05, n = 9), which was associated with reduced FGF-2-induced phosphorylation of phosphatidylinositol 3-kinase (PI3-K), Akt and extracellular regulated kinase 1/2 (ERK1/2) and involved diminished ERK1/2 phosphorylation after PI3-K inhibition (n=3). These results suggest that SHP-2 regulates endothelial cell survival through PI3-K-Akt and mitogen-activated protein kinase pathways thereby strongly affecting new vessel formation. Thus, SHP-2 exhibits a pivotal role in angiogenesis and may represent an interesting target for therapeutic approaches controlling vessel growth. Copyright (C) 2007 S. Karger AG, Basel

Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)

BACKGROUND:Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. METHODOLOGY/PRINCIPAL FINDINGS:Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB's DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. CONCLUSIONS:Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators

Modes of Foreign Entry under Asymmetric Information about Potential Technology Spillovers

This paper studies the effect of technology spillovers on the entry decision of a multinational enterprise into a foreign market. Two alternative entry modes for a foreign direct investment are considered: Greenfield investment versus acquisition. We find that with quantity competition a spillover makes acquisitions less attractive, while with price competition acquisitions become more attractive. Asymmetric information about potential spillovers always reduces the number of acquisitions independently of whether the host country or the entrant has private information. Interestingly, we find that asymmetric information always hurts the entrant, while it sometimes is in favor of the host country

Turnover Intention among Public Sector Health Workforce: Is Job Satisfaction the Issue?

Introduction: The paper explores turnover intention and job satisfaction among healthcare employees of Ministry of Health (MOH) Malaysia. Methods: A nationwide study was carried out in order to identify dimensions of job satisfaction and turnover intention among public healthcare employees. Data was collected by means of self-administered questionnaire and distributed based on quota sampling. Results: The study shows that public healthcare workforce is generally satisfied with their work (mean 3.45). In addition, medical specialists and assistant medical officers were found to be significantly more satisfied than other job designations. However, intention to resign was high among medical specialists, pharmacists and dentists. A high proportion of medical specialists also had received job offers from the private sector. Conclusion: The findings showed that employee turnover may not necessarily be due to job dissatisfaction, but rather due to demand from the private sector. Findings from the study would assist policy-makers with respect to talent management in public healthcare service

A knowledge-driven GIS modeling technique for groundwater potential mapping at the Upper Langat Basin, Malaysia.

The aim of this paper is to use a knowledge-driven expert-based geographical information system (GIS) model coupling with remote-sensing-derived parameters for groundwater potential mapping in an area of the Upper Langat Basin, Malaysia. In this study, nine groundwater storage controlling parameters that affect groundwater occurrences are derived from remotely sensed imagery, available maps, and associated databases. Those parameters are: lithology, slope, lineament, land use, soil, rainfall, drainage density, elevation, and geomorphology. Then the parameter layers were integrated and modeled using a knowledge-driven GIS of weighted linear combination. The weightage and score for each parameter and their classes are based on the Malaysian groundwater expert opinion survey. The predicted groundwater potential map was classified into four distinct zones based on the classification scheme designed by Department of Minerals and Geoscience Malaysia (JMG). The results showed that about 17% of the study area falls under low-potential zone, with 66% on moderate-potential zone, 15% with high-potential zone, and only 0.45% falls under very-high-potential zone. The results obtained in this study were validated with the groundwater borehole wells data compiled by the JMG and showed 76% of prediction accuracy. In addition statistical analysis indicated that hard rock dominant of the study area is controlled by secondary porosity such as distance from lineament and density of lineament. There are high correlations between area percentage of predicted groundwater potential zones and groundwater well yield. Results obtained from this study can be useful for future planning of groundwater exploration, planning and development by related agencies in Malaysia which provide a rapid method and reduce cost as well as less time consuming. The results may be also transferable to other areas of similar hydrological characteristics

Antibiotic susceptibility of Staphylococcus epidermidis among undergraduate students in Malaysia Public University Health Campus

Staphylococcus epidermidis (S. epidermidis) has become one of the major concerns in the hospital setting due to its ability to cause hospital-acquired infection particularly from medical device contamination. The management of S. epidermidis infections become more challenging with the increase of antimicrobial resistance cases over the past years. Limited reports on S. epidermidis antibiotic resistance among healthy people leave uncertainty about the magnitude of antimicrobial resistance spreads among the community. Therefore, this study aimed to identify the antibiotic susceptibility pattern of S. epidermidis isolated from healthy undergraduate students in one of Malaysia public universities-health campuses. Ninety-six hand palm swab samples were collected and undergo several tests, including microscopic, biochemical identification tests and antibiotic susceptibility test for erythromycin, oxacillin, gentamicin, penicillin and tetracycline following Kirby-Bauer test. A total of 43 samples showed the presence of S. epidermidis (44.8%), where 72.1% of the isolates showed resistance towards at least one type of antibiotic. The highest and lowest resistance was observed for penicillin and gentamycin, respectively. Although there is no significant difference of antibiotic susceptibility pattern was observed between genders, the presence of high antibiotic resistance in S. epidermidis among these healthy communities should warrant further investigation since the spreading of the resistant strain could occur in the wider community population without notice

Chemical constituents and antimicrobial activity of Goniothalamus macrophyllus (Annonaceae) from Pasoh Forest Reserve, Malaysia

The essential oils from the twig and root of Goniothalamus macrophyllus were obtained by hydrodistillation and subjected to Gas Chromatography (GC-FID) and Gas Chromatography/Mass Spectrometry (GC-MS) using CBP-5 capillary column in order to determine their chemical composition. Both twig and root oils and four reference standard compounds (-pinene, linalool, geraniol and geranyl acetate) were evaluated for their antimicrobial properties against gram positive and gram negative bacteria, yeast and dermatophyte fungi using broth microdilution methods. The GCMS analysis revealed twenty-one and fourteen compounds from twig and root oils which represented 90.0 and 42.5% of the total oils, respectively. The oils were found to possess the following major components: twig: geranyl acetate (45.5%), geraniol (17.0%), linalool (12.7%) and camphene (7.5%); root: cyperene (9.8%), geranyl acetate (9.4%), geraniol (3.4%) and linalool (2.6%). Other components present in appreciable amounts in both essential oils were -pinene (0.8%) and benzaldehyde (0.5%). The root oil exhibited the most notable inhibitory activity (0.3 mg/ml) against Vancomycin intermediate-resistance Staphylococcus aureus (VISA 24), Staphylococcus epidermidis and Candida albicans. -pinene meanwhile inhibited the bacteria and fungal growth at 0.3 and 2.5 mg/ml. With regards to antimicrobial potential, -pinene superceeds linalool, geraniol and geranyl acetate, respectively.Keywords: Goniothalamus macrophyllus, Annonaceae, essential oils, geranyl acetate, cyperene, geraniol, linalool, -pinene, antimicrobial activityAfrican Journal of Biotechnology Vol. 9(34), pp. 5511-5515, 23 August, 201

Methyl iodide poisoning presenting as a mimic of acute stroke: a case report

<p>Abstract</p> <p>Introduction</p> <p>Stroke mimics are usually non-vascular disease processes. These raise the possibility of a stroke and are common in clinical practice. It is necessary to distinguish these mimics in order to provide early and appropriate management, as well as reduce possible harm on our patient.</p> <p>Case presentation</p> <p>We report the case of a 50-year-old Caucasian man who developed symptoms suggestive of posterior circulation stroke after he was exposed to methyl iodide at his workplace. Results of stroke investigations of our patient were negative, and a detailed occupational history clinched the diagnosis. Acute presentation with a stroke-like picture is rare in cases of methyl iodide poisoning. We have attempted to discuss the differential diagnosis of stroke mimics through a review of literature.</p> <p>Conclusion</p> <p>Stroke mimics are difficult to diagnose in an emergency room situation and may be initially treated as stroke. This case report underlines the importance of history taking, especially occupational history, in the differential diagnosis of stroke. We also stress the need to recognize mimics at presentation in order to arrive at an early and appropriate management of patients.</p