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Petah Tikva, Israel

Dardik R.,Institute of Thrombosis and Hemostasis | Dardik R.,Laboratory of Eye Research | Livnat T.,Institute of Thrombosis and Hemostasis | Livnat T.,Laboratory of Eye Research | And 4 more authors.
Investigative Ophthalmology and Visual Science | Year: 2010

PURPOSE. Choroidal neovascularization (CNV) is the leading cause of vision loss in chorioretinal diseases involving contact between retinal pigment epithelial (RPE) and endothelial cells (ECs). The aim of this study was to investigate changes in the angiogenic potential of ECs induced by RPE-EC interaction in two models of RPE-EC coculture. METHODS. RPE and ECs were grown in contact or noncontact coculture. Selection of ECs was achieved using magnetic beads coated with antibodies specific for EC surface proteins. Angiogenesis was assessed by analyzing the expression of EC genes involved in angiogenesis by RT-PCR. Tube formation on Matrigel was used as a functional angiogenesis assay. Expression and activity of matrix metalloproteases (MMPs) were examined by RT-PCR and zymography, respectively. RESULTS. Coculture of ECs with RPE in the contact model under normoxic conditions induced markedly upregulated EC mRNA expression of 16 genes involved in positive regulation of angiogenesis. Solo ECs subjected to hypoxia demonstrated upregulated expression of the same 16 genes, including VEGF and HIF1. The EC VEGF level was not affected by coculture with RPE in the noncontact model. ECs demonstrated enhanced tube formation on Matrigel after contact coculture with RPE. EC MMP2 mRNA and activity levels were elevated in contact, but not in noncontact, coculture. CONCLUSIONS. Coculture of ECs with RPE under conditions enabling direct EC-RPE contact enhances the proangiogenic potential of ECs under normoxia, to an extent similar to that induced by hypoxia, suggesting that ECs in direct contact with RPE cells might be more prone to pathologic angiogenesis involved in CNV formation. © Association for Research in Vision and Ophthalmology.

Adini B.,National Health Research Institute | Cohen R.,National Health Research Institute | Glassberg E.,Israel Defense Forces | Azaria B.,Israel Defense Forces | And 5 more authors.
Prehospital and Disaster Medicine | Year: 2014

Objectives Inappropriate distribution of casualties in mass-casualty incidents (MCIs) may overwhelm hospitals. This study aimed to review the consequences of evacuating casualties from a bus accident to a single peripheral hospital and lessons learned regarding policy of casualty evacuation. Methods Medical records of all casualties relating to evacuation times, injury severity, diagnoses, treatments, resources utilized and outcomes were independently reviewed by two senior trauma surgeons. In addition, four senior trauma surgeons reviewed impact of treatment provided on patient outcomes. They reviewed the times for the primary and secondary evacuation, injury severity, diagnoses, surgical treatments, resources utilized, and the final outcomes of the patients at the point of discharge from the tertiary care hospital. Results Thirty-one survivors were transferred to the closest local hospital; four died en route to hospital or within 30 minutes of arrival. Twenty-seven casualties were evacuated by air from the local hospital within 2.5 to 6.15 hours to Level I and II hospitals. Undertriage of 15% and overtriage of seven percent were noted. Four casualties did not receive treatment that might have improved their condition at the local hospital. Conclusions In MCIs occurring in remote areas, policy makers should consider revising the current evacuation plan so that only immediate unstable casualties should be transferred to the closest primary hospital. On site Advanced Life Support (ALS) should be administered to non-severe casualties until they can be evacuated directly to tertiary care hospitals. First responders must be trained to provide ALS to non-severe casualties until evacuation resources are available. © 2013 World Association for Disaster and Emergency Medicine.

Zvulunov A.,Pediatric Dermatology Unit | Zvulunov A.,Ben - Gurion University of the Negev | Shkalim V.,Tel Aviv University | Ben-Amitai D.,Pediatric Dermatology Unit | And 3 more authors.
Journal of the American Academy of Dermatology | Year: 2012

Background: Some authorities consider alopecia mucinosa (AM)/follicular mucinosis (FM) to invariably represent mycosis fungoides (MF). This understanding of AM/FM derives from observations in adults. Objectives: We sought to explore the clinicopathologic features and natural history of pediatric AM/FM. Methods: Medical records were searched for children given the diagnosis of AM/FM from 1998 through 2009. Diagnosis of AM/FM was defined as the presence of well-demarcated hairless plaques with follicular prominence plus an abundance of mucin on histopathologic examination. Results: Forty children with a clinical diagnosis of AM/FM were identified. Nine did not meet the inclusion criteria. In the 31 remaining cases (16 boys, 15 girls) the mean age at onset was 9 ± 3.5 years. Histopathologic examination showed folliculotropism in 28 patients (90%) and epidermotropism in 15 (48%). Twelve cases fulfilled the International Society of Cutaneous Lymphomas (ISCL) diagnostic criteria for early MF. The histopathologic findings were typical of MF in only in two of these cases. T-cell receptor gene rearrangement was positive in 3 of 6 (50%) of tested samples, one in a patient who fulfilled the ISCL criteria for early MF. Mean duration of follow-up was 6.2 ± 3.7 years. All skin lesions resolved and none persisted or recurred. Hodgkin lymphoma was diagnosed 6 months after diagnosis of AM/FM in one patient. Limitations: This was a retrospective study. Conclusions: Although some pediatric cases meet the diagnostic criteria for MF, AM/FM cannot be regarded unequivocally as early follicular MF in this age group. We suggest the current diagnostic criteria for early MF should exclude children with AM/FM. Long-term follow-up of children with AM/FM is nevertheless warranted.

Barliya T.,The Blood Center | Mandel M.,The Blood Center | Livnat T.,Institute of Hematology | Weinberger D.,Beilinson Medical Center | And 3 more authors.
PLoS ONE | Year: 2011

The perihydroxylated perylene quinone hypericin has been reported to possess potent anti-metastatic and antiangiogenic activities, generated by targeting diverse crossroads of cancer-promoting processes via unique mechanisms. Hypericin is the only known exogenous reagent that can induce forced poly-ubiquitination and accelerated degradation of heat shock protein 90 (Hsp90) in cancer cells. Hsp90 client proteins are thereby destabilized and rapidly degraded. Hsp70 client proteins may potentially be also affected via preventing formation of hsp90-hsp70 intermediate complexes. We show here that hypericin also induces enhanced degradation of hypoxia-inducible factor 1α (HIF-1α) in two human tumor cell lines, U87-MG glioblastoma and RCC-C2VHL-/- renal cell carcinoma and in the non-malignant ARPE19 retinal pigment epithelial cell line. The hypericin-accelerated turnover of HIF-1α, the regulatory precursor of the HIF-1 transcription factor which promotes hypoxic stress and angiogenic responses, overcomes the physiologic HIF-1α protein stabilization which occurs in hypoxic cells. The hypericin effect also eliminates the high HIF-1α levels expressed constitutively in the von-Hippel Lindau protein (pVHL)-deficient RCC-C2VHL-/- renal cell carcinoma cell line. Unlike the normal ubiquitin-proteasome pathway-dependent turnover of HIF-α proteins which occurs in normoxia, the hypericin-induced HIF-1α catabolism can occur independently of cellular oxygen levels or pVHL-promoted ubiquitin ligation of HIF-1α. It is mediated by lysosomal cathepsin-B enzymes with cathepsin-B activity being optimized in the cells through hypericin-mediated reduction in intracellular pH. Our findings suggest that hypericin may potentially be useful in preventing growth of tumors in which HIF-1α plays pivotal roles, and in pVHL ablated tumor cells such as renal cell carcinoma through elimination of elevated HIF-1α contents in these cells, scaling down the excessive angiogenesis which characterizes these tumors. © 2011 Barliya et al.

Shemer A.,Tel Aviv University | Shemer A.,Sheba Medical Center | Plotnik I.B.,Tel Aviv University | Davidovici B.,Tel Aviv University | And 5 more authors.
JDDG - Journal of the German Society of Dermatology | Year: 2013

Objective To compare the efficacy and safety of fluconazole and griseofulvin in the treatment of tinea capitis. Patients and Methods Patients with tinea capitis (n = 113) with positive fungal cultures entered the study. The patients were divided into four groups with different treatment regimes. Two groups received griseofulvin 15 or 25 mg/kg/day and two groups received fluconazole 4 or 6 mg/kg/day, all for up to 12 weeks. Results Griseofulvin was found to be slightly better than fluconazole. The lower doses for both griseofulvin and fluconazole required significantly longer treatment duration until mycological cure than the higher doses, independent of the fungus type. Conclusions Since no significant difference was found between the drugs, it is suggested that the choice should be based on tolerability, availability and cost of the drugs. © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.

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