Distinct domains of alphaIIbbeta3 support different aspects of outside-in signal transduction and platelet activation induced by LSARLAF, an alphaIIbbeta3 interacting peptide

The peptide LSARLAF causes alphaIIbeta3-dependent platelet activation exemplified by secretion, aggregation, spreading and adhesion on fibrinogen, and tyrosine phosphorylation. alphaIIIbeta3-dependent outside-in signal transduction induced by LSARLAF was investigated in variant thrombasthenic platelets which lack most of the cytoplasmic domain of the integrin beta3 subunit (alphaIIbbeta3 delta724). These studies revealed that only certain aspects of this alphaIIbbeta3-dependent outside-in signaling were affected by the beta3 truncation. Specifically, alphaIIbbeta3 delta724 supported LSARLAF-induced platelet aggregation, agglutination and secretion, but failed to trigger cytoskeletal reorganization and platelet spreading on fibrinogen, despite the fact that PMA-induced non alphaIIbbeta3 mediated signaling caused spreading of these platelets on fibrinogen. Thus, distinct domains of alphaIIbbeta3 are required to support different aspects of LSARLAF-induced platelet activation. Furthermore, these studies suggest that not all alphaIIbbeta3-dependent platelet responses require an intact beta3 cytoplasmic tail.     

Systemic hematologic effects of PEG-rHuMGDF-induced megakaryocyte hyperplasia in mice

PEG-rHuMGDF injected daily in normal mice causes a rapid dose-dependent increase in megakaryocytes and platelets. At the same time that platelet numbers are increased, the mean platelet volume (MPV) and platelet distribution width (PDW) can be either decreased, normal, or increased depending on the dose and time after administration. Thus, PEG-rHuMGDF at a low dose causes decreases in MPV and PDW, MGDF at an intermediate dose causes an initial increase followed by a decrease in MPV and PDW, and PEG-rHuMGDF at higher doses causes an increase in MPV and PDW followed by a gradual normalization of these platelet indices. In addition to the expected thrombocytosis after 7 to 10 days of daily injection of high doses of PEG-rHuMGDF, a transient decrease in peripheral red blood cell numbers and hemoglobin is noted accompanied in the bone marrow by megakaryocytic hyperplasia, myeloid hyperplasia, erythroid and lymphoid hypoplasia, and deposition of a fine network of reticulin fibers. Splenomegaly, an increase in splenic megakaryocytes, and extramedullary hematopoiesis accompany the hematologic changes in the peripheral blood and marrow to complete a spectrum of pathologic features similar to those reported in patients with myelofibrosis and megakaryocyte hyperplasia. However, all the PEG-rHuMGDF-initiated hematopathology including the increase in marrow reticulin is completely and rapidly reversible upon the cessation of administration of PEG-rHuMGDF. Thus, transient hyperplastic proliferation of megakaryocytes does not cause irreversible tissue injury. Furthermore, PEG-rHuMGDF completely ameliorates carboplatin-induced thrombocytopenia at a low-dose that does not cause the hematopathology associated with myelofibrosis.     

South‐East Asia study alliance guidelines on the management of acne vulgaris in South‐East Asian patients

The management of acne in South‐East Asia is unique, as Asian skin and local variables require a clinical approach unlike that utilized in other parts of the world. There are different treatment guidelines per country in the region, and a group of leading dermatologists from these countries convened to review these guidelines, discuss current practices and recent advances, and formulate consensus guidelines to harmonize the management of acne vulgaris in the region. Emphasis has been placed on formulating recommendations to impede the development of antibiotic resistance in Propionibacterium acnes. The group adopted the Acne Consensus Conference system for grading acne severity. The group recommends that patients may be treated with topical medications including retinoids, benzoyl peroxide (BPO), salicylic acid, a combination of retinoid and BPO, or a combination of retinoids and BPO with or without antibiotics for mild acne; topical retinoid with topical BPO and a oral antibiotic for moderate acne; and oral isotretinoin if the patient fails first‐line treatment (a 6‐ or 8‐week trial of combined oral antibiotics and topical retinoids with BPO) for severe acne. Maintenance acne treatment using topical retinoids with or without BPO is recommended. To prevent the development of antibiotic resistance, topical antibiotics should not be used as monotherapy or used simultaneously with oral antibiotics. Skin care, comprised of cleansing, moisturizing and sun protection, is likewise recommended. Patient education and good communication is recommended to improve adherence, and advice should be given about the characteristics of the skin care products patients should use.     

Factor structure of posttraumatic stress disorder symptoms in the Australian general population

The tripartite model of posttraumatic stress disorder (PTSD) articulated in DSM-IV has received limited empirical support. Over the past decade, a burgeoning literature on PTSD symptom structure has accumulated suggesting several alternative models. Elucidating the latent structure of PTSD has important clinical and theoretical implications. This paper presents the first confirmatory factor analytic investigation of PTSD symptoms in an epidemiologically based trauma-exposed sample from Australia. Data from a subsample of respondents from the 2007 National Survey of Mental Health and Wellbeing (NSMHWB; n = 2677) were submitted to confirmatory factor analysis and several alternative conceptual models were tested. Empirical support was found for an intercorrelated four-factor model reflecting re-experiencing, avoidance, dysphoria, and hyperarousal symptoms. Given that the DSM is currently under revision, research addressing structural validity concerns is especially timely. The present findings renew calls in the structural literature suggesting that the structure of PTSD should be revised in DSM-V.     

Topical imiquimod in the treatment of extramammary Paget's disease: A 10 year retrospective analysis in an Asian tertiary centre

Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma usually found in apocrine‐rich areas. Although surgery remains standard treatment, topical imiquimod has emerged as a promising drug for the treatment of EMPD in recent years. We present our experience in treating EMPD in Asian skin successfully with topical imiquimod 5% cream, over the past 10 years in our tertiary institution.     

Vaginal Perforation due to Jet Ski Accident

A case of full thickness vaginal perforation into the peritoneal cavity resulting from a jet-skiing accident is presented. Attention is drawn to the previously reported cases of similar injuries due to high speed water sports, and the need for adequate protective clothing in all people undertaking such sports.     

Factor VIIa induced release of von Willebrand factor from human umbilical vein endothelial cells by a tyrosine kinase dependent pathway

The interaction of FVIIa with surface-bound tissue factor (TF) induces various cellular changes including cytosolic Ca2+ signals. The release of von Willebrand factor (VWF) from endothelial cell stores may be triggered by an elevation in cytosolic free Ca2+, therefore we investigated the effect of rFVIIa on the release of VWF from human umbilical vein endothelial cells (HUVEC). We show here that rFVIIa induces the release of VWF from HUVEC with or without prestimulation with lipopolysaccharide (LPS). The effect of rFVIIa was dose dependent. However, the release of VWF by HUVEC in response to rFVIIa was significantly greater with LPS prestimulation (3.18 times control) than without LPS prestimulation (1.45 times control) (p < 0.001). Cytosolic Ca2+ signals were detectable only after LPS prestimulation of HUVEC and these were small compared to those elicited by thrombin. No effect on rFVIIa induced release of VWF was seen in the presence of hirudin, site inactivated rFVIIa or the protein kinase C (PKC) inhibitor staurosporine. However, a tyrosine kinase inhibitor genistein, inhibited the rFVIIa induced release of VWF. These data show that release of VWF can occur without involvement of the cytosolic Ca2+/ PKC pathway. FVIIa induced VWF release from endothelial cells may have in vivo significance at sites of TF expression.