Target fishing reveals PfPYK-1 and PfRab6 as potential targets of an antiplasmodial 4-anilino-2-trichloromethylquinazoline hit compound.

We present investigations about the mechanism of action of a previously reported 4-anilino-2-trichloromethylquinazoline antiplasmodial hit-compound (Hit A), which did not share a common mechanism of action with established commercial antimalarials and presented a stage-specific effect on the erythrocytic cycle of P. falciparum at 8 < t < 16 h. The target of Hit A was searched by immobilising the molecule on a solid support via a linker and performing affinity chromatography on a plasmodial lysate. Several anchoring positions of the linker (6,7 and 3') and PEG-type linkers were assessed, to obtain a linked-hit molecule displaying in vitro antiplasmodial activity similar to that of unmodified Hit A. This allowed us to identify the PfPYK-1 kinase and the PfRab6 GTP-ase as potential targets of Hit A.

Preventing the contamination of hospital personnel by cytotoxic agents: evaluation and training of the para-professional healthcare workers in oncology units.

This study was specifically focused on para-professional healthcare workers (PHCWs) who handle cytotoxic drugs and contaminated wastes at the Public Teaching Hospitals of Marseille (AP-HM), France. It first aimed at evaluating the knowledge and professional practice of the PHCWs who belong to a personnel category among the less informed and protected in hospitals. In a second time, this study also proposed to raise awareness, educate and train the staff on protective measures to minimise the exposure of the PHCWs to the potential toxicity of anticancer chemotherapy agents (or metabolites) when cleaning and handling both cytotoxic drugs and wastes. Among the 11 oncology units evaluated, 82% completed an assessment survey, 63% of which were PHCWs. Out of nine oncology units assessed, 89% reported limited knowledge of the general risk and of the safe handling of cytotoxic drugs, 89% reported using vinyl gloves which are the less protective ones. Forty-four per cent of the units used wet sweeping techniques for cleaning the floors, and 11% of the units did not have specific procedures for cleaning the equipments used for collecting contaminated excreta. Protective outer apparel was not always worn and chemotherapy wastes were not managed consistently between all units. Standardized procedures and guidelines to prevent occupational exposure were not used by PHCWs. More education and training are needed to improve safety.

Mechanical testing of spider silk at cryogenic temperatures.

A method and results for mechanical testing of spider silk in extreme environments is presented. In particular, silk from the spider Steatoda triangulosa is harvested, and samples are subjected to cryogenic temperatures by means of liquid nitrogen submersion. Samples are destructively tested while immersed in liquid nitrogen, and the stress-strain characteristics are compared to those of silk at room temperature. The strength, elasticity, and toughness of the cryogenically submersed silk are determined. It is found that on average, silk is 64% stronger while immersed in liquid nitrogen (i.e., at -196°C). The testing method could also be used for testing of silk in chemically hostile environments.

[Community-acquired methicillin-resistant Staphylococcus aureus in a dermatology outpatient clinic]. / Les souches de Staphylococcus aureus méticilline-résistant communautaires en consultation externe hospitalière de dermatologie.

BACKGROUND: Community-acquired cutaneous infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a growing concern. These bacteria may produce Panton-Valentine leucocidin potentially leading to necrotizing pneumonia. We studied the prevalence of MRSA and Panton-Valentine leucocidin in dermatology clinic outpatients in order to adapt therapy where possible. PATIENTS AND METHODS: This was a prospective study including all patients seen at a dermatology outpatient clinic between 1st March 2005 and 31st December 2006 and presenting mucocutaneous bacteriological samples. The main MRSA risk factors studied were frequent hospital consultations, hospitalization, antibiotic therapy within the last three months and community life. The following risk factors were also analysed, although less routinely: substance abuse, immunosuppression, diabetes mellitus, recent travel abroad and a history of similar lesions. RESULTS: One hundred and twenty-two patients were included in the study and 235 samples (143 lesion samples and 92 nasal swabs) were carried out and S. aureus was isolated in 68 patients (56%). Twelve patients had MRSA (17.6%); seven of these were normal outpatients but five attended frequent hospital consultations (7.3%). MRSA resistance rates were as follows: 64% to ofloxacin, 36% to amikacin and erythromycin, 27% to fusidic acid, 9.1% to sulfamethoxazole-trimethoprim and 0% to pristinamycin. Community life was the only significant risk factor for MRSA in this study (p=0.045). Four of the 11 MRSA strains tested produced Panton-Valentine leucocidin. CONCLUSION: Dermatologists are increasingly faced with cutaneous infections caused by community-acquired MRSA. Bacterial samples should be taken routinely and probabilistic antibiotic therapy for MRSA instituted in severe infections.

[Acitretin-induced pneumonia: an underestimated complication of treatment of psoriasis]. / La pneumopathie associée à l'acitrétine: une complication du traitement du psoriasis à ne pas méconnaître.

INTRODUCTION: Retinoids are known to induce side effects which can be severe. Alveolar and interstitial pneumonia of uncertain pathogenesis can rarely occur when retinoid are used among patients with psoriasis. EXEGESIS: We report an observation of acute respiratory distress beginning 26 days after introduction of acitretin, a second-generation retinoid. Treatment withdrawal and corticotherapy allow a spectacular amelioration of respiratory conditions. CONCLUSION: Pneumonia induced by retinoid must be known as a side effect of treatment of psoriasis.

Role of platelet-activating factor in acid-induced esophageal mucosal injury.

Studies on the pathophysiology of reflux esophagitis have focused on the associated motility and/or structural abnormalities, with relatively little attention directed to inflammatory mediators involved in the acid-induced mucosal injury. Mast cells line the subepithelial lamina propria in both humans and the opossum model, and are ideally positioned to respond to luminal agents that cross the mucosal barrier. To determine whether certain mast cell mediators are involved in acid-induced mucosal injury, epithelial injury scores following 60 min of luminal perfusion of the opossum esophagus with 100 mM HCl were compared in the presence and absence of two different mast cell stabilizers (disodium cromoglycate and doxantrazole) or the selective platelet-activating factor antagonist TCV-309. In control animals acid perfusion caused release of PAF and significant epithelial injury, characterized by epithelial sloughing and cleft formation. This injury was unaffected by pretreatment with disodium cromoglycate or doxantrazole but was completely prevented by TCV-309 (histology damage score, 2.40+/-0.28 in controls vs 0.50 +/- 0.14 in TCV-309-treated animals). These studies suggest that platelet-activating factor is an important mediator of acid-induced esophageal mucosal damage.

[A young woman with granulomatous mastitis: a corynebacteria may be involved in the pathogenesis of these disease]. / Mastite granulomateuse récidivante chez une jeune femme: rôle potentiel de "corynebacterium kroppenstedtii".

INTRODUCTION: The granulomatous mastitis is an inflammatory pseudotumor of the breast of which evolution benign but likely to generate important morphological after-effects among young women. This anatomoclinic entity of dubious etiology until these last years poses a problem of differential diagnosis with other etiologies of granulomatosis and especially with inflammatory carcinoma of the breast. The infectious theory is actually based on solid arguments and mainly explains the physiopathology of this affection. INTERPRETATION: A 26 years old young woman developed an inflammatory tumor of the left breast of which the catch of load by surgery and an antibiotherapy had shown trailing local continuations and of the esthetic after-effects. One year later, a very inflammatory repetition on the level of the right breast was dealt with in a different way: by steroids and immunomodulating drugs associated with iterative punctures with the purulent collections, the objective being to be less dilapidating that left side. The initial answer was rather favorable and encouraging but the purulent reappearance bulky granulomas with sinus way made reconsider the therapeutic attitude and antibiotics were undertaken after description of a lipophilic corynebactery in the material of puncture (Corynebacteria kroppenstedtii). The effectiveness of the amoxicilline introduced on the data of the antibiogram was undeniable. CONCLUSION: This observation illustrates the therapeutic and diagnostic difficulties of an exceptional affection. Potentially accessible to antibiotics it generally requires a joint surgical assumption of responsibility, at the same time to ensure the histological diagnosis but also with a therapeutic aim. The interest of steroids and the immunomodulation by methotrexate is debatable, these treatments cannot however be conceived without antibiotherapy and sometimes surgery.

Citizen empowerment: a developmental perspective.

Since the late 1970s, the notion of empowerment has appeared with increasing frequency in discussion of preventive social and community intervention. While the idea of empowerment is intuitively appealing both for theory and practice, its applicability has been limited by continuing conceptual ambiguity. Based on a small N study of emerging citizen leaders in grassroots organizations, this article proposes a view of empowerment as a necessarily long-term process of adult learning and development. In this framework, empowerment is further described as the continuing construction of a multi-dimensional participatory competence. This conception encompasses both cognitive and behavioral change. Implications for practice are also addressed.

The Peruvian brothel as sexual dispensary and social arena.

This ethnographic description of a Peruvian brothel suggests that the organization of the brothel is determined to a considerable extent by social considerations as well as sexual needs. The authors describe a temporal arrangement that provides for a separation and differential treatment of two social groupings or classes that patronize the brothel. The wealthier and older clients are provided with sexual services within a setting that might be described as a "macho theater" in which social needs are also allowed expression. The less wealthy classes are served in almost purely biological fashion and can ill-afford within this setting the "macho" practices provided to other more wealthy clients.