Design, synthesis and antiparasitic evaluation of click phospholipids

A library of seventeen novel ether phospholipid analogues, containing 5-membered heterocyclic rings (1,2,3-triazolyl, isoxazolyl, 1,3,4-oxadiazolyl and 1,2,4-oxadiazolyl) in the lipid portion were designed and synthesized aiming to identify optimised miltefosine analogues. The compounds were evaluated for their in vitro antiparasitic activity against Leishmania infantum and Leishmania donovani intracellular amastigotes, against Trypanosoma brucei brucei and against different developmental stages of Trypanosoma cruzi. The nature of the substituents of the heterocyclic ring (tail) and the oligomethylene spacer between the head group and the heterocyclic ring was found to affect the activity and toxicity of these compounds leading to a significantly improved understanding of their structure\u2013activity relationships. The early ADMET profile of the new derivatives did not reveal major liabilities for the potent compounds. The 1,2,3-triazole derivative 27 substituted by a decyl tail, an undecyl spacer and a choline head group exhibited broad spectrum antiparasitic activity. It possessed low micromolar activity against the intracellular amastigotes of two L. infantum strains and T. cruzi Y strain epimastigotes, intracellular amastigotes and trypomastigotes, while its cytotoxicity concentration (CC50) against THP-1 macrophages ranged between 50 and 100 \ub5M. Altogether, our work paves the way for the development of improved ether phospholipid derivatives to control neglected tropical diseases

Pediculosis capitis: Treatment options among schoolchildren in Greece

Background: Pediculosis capitis remains a significant health problem worldwide. Purpose: It was to record the preferred treatment options against pediculosis capitis in school-age children in Greece. Method and Material: A randomly selected, stratified sample of schools from all over Greece was used. A questionnaire with closed and open-type questions was used. Five thousand, eighty four questionnaires were distributed and 2792 returned. Descriptive statistics was conducted. Results: Median age of the children was 8 (3-13) years. 88,6% of the parents answered the would not visit a dermatologist in the case of pediculosis. Insecticides were the treatment of choice in most cases (80 %), while louse comb as a single treatment was preferred by 1 % of the parents. Conclusion: Drugs remain the main treatment choice in Greece. Dermatologists infrequently treat patients with pediculosis capitis

Drugs associated with bullous pemphigoid: role of ΗΜG-COa reductase inhibitors

[No abstract available

The effect of Apremilast on signal transduction and IL-10 production in CD39high regulatory B cells in patients with psoriatic arthritis

Background. IL-10-producing regulatory B cells (Bregs) are of great importance in autoimmunity, as they inhibit proinflammatory T cells. We have shown that IL-10-producing Bregs in psoriatic arthritis(PsA) were decreased and inversely correlated with IFNγ+T cells (TH1 cells) and IL-17+ T cells (TH17 cells). B cells with overexpression of CD39 have also inhibitory effects on proinflammatory T cells. Preliminary results. Our preliminary data showed that Apremilast, a phosphodiesterase-4(PDE-4) inhibitor, used in the treatment of PsA and psoriasis (Ps) increased IL-10-producing Bregs and reduced IFNγ+CD3+ T cells and IL-17+CD3+ T cells. We also found reduced activation of p38MAP kinase and the transcription factor STAT3, two important signaling pathways of IL-10 production, in PsA. Specific Aims. The aim of this research proposal is to study for the first time the immunomodulatory effect of Apremilast on signaling pathways in peripheral blood mononuclear cells (PBMCs) and CD39high B cells in PsA and Ps. Methods. We will study CD39 expression in B cells from patients with PsA and Ps before and after Apremilast treatment and their relation to IFNγ+ and IL-17+ T cells. Activation of CREB (cAMP response element-binding protein), STAT3, and p38MAPK in PBMCs and CD39high B cells from patients with PsA and Ps before and after Apremilast. The effect of CD39high B cells on T cell IFNγ and IL-17 production will also be studied. Significance. This study will elucidate the molecular pathways of Apremilast and better define Bregs in PsA and Ps. © Sakkas L I, Mavropoulos A, Zafiriou E, Roussaki-Schulze A, Bogdanos D P

Influence of psychological and clinical factors on postoperative pain and narcotic consumption

Demographic, psychological and clinical factors influencing postoperative pain and narcotic analgesic requirements in 162 patients undergoing elective operations under general anesthesia were studied. Eysencks Personality Questionnaire, Foulds Hostility Questionnaire, Zung's Anxiety-Depression (self-rating) Scales and the 43 Item Life Events Inventory by Holmes and Rahe were used. Clinical correlates such as surgical department, outcome of the operation, patient's knowledge of the diagnosis, were studied. Using multiple regression analysis the following results were obtained: postoperative pain levels increase with higher score of extroverted hostility (p = 0.038), abdominal surgery (p = 0.004) longer stay at hospital postoperatively (p = 0.15) and higher educational status (p = 0.13). Postoperative narcotic requirements increase with increased postoperative pain levels (p = 0.039) and preoccupation with pain postoperatively (p = 0.025), preoperative analgesic drug use (p = 0.0 17), abdominal surgery (p = 0.009) and longer stay at hospital preoperatively (p = 0.016). Also the department in which the patients were hospitalized influenced narcotic consumption

Effect of TNF-α inhibitors on transcriptional levels of pro-inflammatory interleukin-33 and Toll-like receptors-2 and -9 in psoriatic plaques

Tumor necrosis factor (TNF)-α inhibitors are considered to be effective in the treatment of psoriatic plaques, although the precise therapeutic pathway is not clear. Pro-inflammatory molecules, such as Toll-like receptor (TLR)-2 and -9 and interleukin (IL)-33, a member of the IL-1 receptor/TLR superfamily, have been found to be expressed in psoriatic plaques. The aim of the present study was to investigate whether TNF-α inhibitor treatment has an effect on the expression of IL-33 and TLR-2 and -9 in psoriatic plaques. Seventeen patients with psoriatic plaques were treated with a TNF-α inhibitor (etanercept or infliximab) for 12 weeks in an open-label study, and the transcriptional levels of IL-33 and TLR-2 and -9 were determined by reverse transcription-quantitative polymerase chain reaction in paired biopsies of psoriatic plaques obtained at baseline (B) and following the 12 weeks of treatment (P). The psoriasis area severity index (PASI) score was also determined. At B, elevated IL-33 and TLR-2 mRNA levels were observed in all cases, while TLR-9 showed elevated mRNA levels in 76% of cases. At P, reductions in the mRNA levels of IL-33, TLR-2 and TLR-9 were observed, with TLR-2 and -9 levels exhibiting significant reductions (P<0.0001, Wilcoxon signed-rank test). PASI scores were significantly reduced by the treatment (P<0.0001, Wilcoxon signed-rank test) and the changes in PASI scores exhibited a significant positive Pearson's correlation with the P/B mRNA expression ratios of TLR-2 or -9 in males (P<0.05), particularly in the etanercept group (P<0.0001). The findings support the efficacy of anti-TNF-α treatment on the innate immune response in psoriatic skin, with a focus on TLR-2 and -9 inhibition, suggesting their role in the pathogenic mechanism of plaque psoriasis, which may be associated with gender. © 2015, Spandidos Publications. All rights reserved