Isolation, structure, and antibacterial activity of phaeosphenone from a Phaeosphaeria sp. discovered by antisense strategy

Ribosomal protein S4 (RPSD), a part of the ribosomal small subunit, is one of the proteins that is a part of the ribosomal machinery and is a potential new target for the discovery of antibacterial agents. Continued screening of microbial extracts using antisense-sensitized rpsD Staphylococcus aureus strain led to the isolation of a new dimeric compound, phaeosphenone (2). Compound 2 showed broad-spectrum antibacterial activity against Gram-positive bacteria, exhibiting MIC values ranging from 8 to 64 microg/mL. Phaeosphenone showed the highest sensitivity for Streptococcus pneumoniae (8 microg/mL) and inhibited the growth of Candida albicans with an MIC of 8 microg/mL. Phaeosphenone showed a modest selectivity for the inhibition of RNA synthesis over DNA and protein synthesis in S. aureus.     

Enterocytozoon bieneusi (microsporidia) in clinical samples from immunocompetent individuals in Tenerife, Canary Islands, Spain

Microsporidia are newly emerging pathogens of humans and animals, with Enterocytozoon bieneusi being the most common causal agent in human microsporidiosis. To determine the presence of E. bieneusi, 273 clinical samples (40 urine, 156 stools, 37 sputum, 9 bronchial aspirates, 5 bronchial washes and 26 pleural fluids) from immunocompetent patients, mainly suffering diarrhoea or pneumonia, in Tenerife, Canary Islands, Spain were analysed using light microscopy after staining with Weber's chromotrope and by PCR/hybridisation with a specific probe designed to increase the sensitivity of the identification. In this study, detection of E. bieneusi after PCR/hybridisation is reported in 18 (11.54%) of 156 stool samples, 1 (2.5%) of 40 urine samples and 6 (16.22%) of 37 sputum samples. To our knowledge, these are the first reports of E. bieneusi in this subtropical region, showing the increased importance of these parasites as emerging pathogens worldwide.     

Fungus-elicited metabolites from plants as an enriched source for new leishmanicidal agents: antifungal phenyl-phenalenone phytoalexins from the banana plant (Musa acuminata) target mitochondria of Leishmania donovani promastigotes

Two antifungal phenyl-phenalenone phytoalexins isolated from the banana plant (Musa acuminata) elicited with the fungus Fusarium oxysporum, together with a methoxy derivative of one of them and two epoxide precursors of their chemical synthesis, were tested for leishmanicidal activity on Leishmania donovani promastigotes and L. infantum amastigotes. Drugs inhibited proliferation of both forms of the parasite with a 50% lethal concentration range between 10.3 and 68.7 micro g/ml. Their lethal mechanism was found linked to the respiratory chain by a systematic approach, including electron microscopy, measurement of the oxygen consumption rate on digitonin-permeabilized promastigotes, and enzymatic assays on a mitochondrial enriched fraction. Whereas the whole set of compounds inhibited the activity of fumarate reductase in the mitochondrial fraction (50% effective concentration [EC(50)] between 33.3 and 78.8 micro g/ml) and on purified enzyme (EC(50) = 53.3 to 115 micro g/ml), inhibition for succinate dehydrogenase was only observed for the two phytoalexins with the highest leishmanicidal activity: anigorufone and its natural analogue 2-methoxy-9-phenyl-phenalen-1-one (EC(50) = 33.5 and 59.6 micro g/ml, respectively). These results provided a new structural motif, phenyl-phenalenone, as a new lead for leishmanicidal activity, and support the use of plant extracts enriched in antifungal phytoalexins, synthesized under fungal challenge, as a more rational and effective strategy to screen for new plant leishmanicidal drugs.     

Teaching Nursing Students to Stop the Bleed Emergency Preparedness Education for Mass Casualty Events

There has been a rise in mass casualty events over the past decade. The Stop the Bleed initiative aims to increase survivorship in these events by teaching the basics of bleeding control. This educational intervention was conducted to instruct nursing students on the basics of bleeding control and emergency preparedness. The ultimate result of this project is that 143 future nurses that now have the skills to stop life-threatening bleeding in an emergency situation.     

Evaluation of Acanthamoeba Myosin-IC as a Potential Therapeutic Target

Members of the genus Acanthamoeba are facultative pathogens of humans, causing a sight-threatening keratitis and a fatal encephalitis. We have targeted myosin-IC by using small interfering RNA (siRNA) silencing as a therapeutic approach, since it is known that the function of this protein is vital for the amoeba. In this work, specific siRNAs against the Acanthamoeba myosin-IC gene were developed. Treated and control amoebae were cultured in growth and encystment media to evaluate the induced effects after myosin-IC gene knockdown, as we have anticipated that cyst formation may be impaired. The effects of myosin-IC gene silencing were inhibition of cyst formation, inhibition of completion of cytokinesis, inhibition of osmoregulation under osmotic stress conditions, and death of the amoebae. The finding that myosin-IC silencing caused incompletion of cytokinesis is in agreement with earlier suggestions that the protein plays a role in cell locomotion, which is necessary to pull daughter cells apart after mitosis in a process known as “traction-mediated cytokinesis”. We conclude that myosin-IC is a very promising potential drug target for the development of much-needed antiamoebal drugs and that it should be further exploited for Acanthamoeba therapy.     

Portal thrombosis: late postoperative prevalence in Mansoni's schistosomiasis

BACKGROUND/AIMS: Splenectomy with esophagogastric devascularization and distal splenorenal anastomosis are used for the treatment of bleeding esophageal varices in Mansoni's hepatosplenic schistosomiasis. Portal thrombosis followed by ascitis has been observed in the early postoperative phase, but there are no studies about the spontaneous and late postoperative prevalence of this vascular complication. The aim was to evaluate the spontaneous and late postoperative prevalence of total portal vein thrombosis and of ascitis in these patients. METHODOLOGY: US-Doppler examination was performed on 168 patients divided in three groups: 1) 92 non-operated (preoperative); 2) 62 after splenectomy with esophageal devascularization, 3) 14 after distal splenorenal anastomosis. The presence of ascitis was sought in all. RESULTS: Group 1 had 5.43% (5/92) of spontaneous total portal vein thrombosis, groups 2 and 3, presented 19.35% (12/62) and 50.00% (7/14) in the late postoperative follow-up, respectively. The Fisher's test showed that group 3 had higher incidence of this vascular occlusive complication (p = 0.038). No ascites were found. CONCLUSIONS: Surgical treatment of portal hypertension boosts the natural tendency to total portal vein thrombosis in this disease. The difference in the occurrence of this vascular complication during the late postoperative phase suggests the existence of a hemodynamic factor determined by the surgical technique.