Eurocristatine,a new diketopiperazine dimer from the marine sponge-associated fungus Eurotium cristatum

A new diketopiperazine dimer, eurocristatine (1), was isolated, in addition to eight known metabolites including the anthraquinones erythroglaucin, physcion, catenarin, emodin and the dioxopiperazine alkaloids echinulin, neoechinulin A, neoechinulin E, variecolorin J, from the culture of the sponge-associated fungus Eurotium cristatum KUFC 7356. The structure of eurocristatine (1) was established based on 1D and 2D NMR spectral analysis as well as HRESIMS, and the absolute configuration of its stereogenic carbons was determined by an X-ray crystallographic analysis. Eurocristatine (1) did not exhibit cytotoxic, antibacterial or antifungal activity.     

Inhibition of PI3K increases oxaliplatin sensitivity in cholangiocarcinoma cells

Background  

Resistance of cholangiocarcinoma to chemotherapy is a major problem in cancer treatment. The mechanism of resistance is believed to involve phosphoinositide-3- kinase (PI3K)/Akt activation. Although the platinum-containing compound oxaliplatin has been extensively used in the treatment of several solid tumors, recent data regarding its use to treat cholangiocarcinoma are ambiguous. Oxaliplatin resistance in this disease could potentially involve PI3K pathways. We, therefore, examined the effects of PI3K pathways in cholangiocarcinoma cells in modulating oxaliplatin resistance.     

Evaluation of procedures to determine absolute density of Plasmodium vivax ookinetes

The ookinete is the key determinant of infection within the mosquito vector, yet there are few population studies of ookinetes in nature. This investigation compared different techniques used to estimate ookinete densities in mosquitoes. Laboratory-reared Anopheles dirus mosquitoes were fed on gametocytemic blood drawn from 7 Plasmodium vivax patients at a malaria clinic in Mae Sot, Thailand. At 20-26 hr, bloodmeals were excised. Three techniques were evaluated, i.e., hemacytometer counts under phase-contrast microscope, Giemsa staining of bloodmeal smears, and immunofluorescent staining with a monoclonal antibody specific against the 25-kDa antigen expressed on the surface of P. vivax zygotes and ookinetes. Additional mosquitoes were dissected at day 10 for oocysts. The hemacytometer method was the simplest and quickest method but lacked precision at low ookinete densities. Immunofluorescent staining was the most sensitive, accurate, and the only method that enabled unequivocal detection of zygotes. Bloodmeals contained a mixture of zygotes, retorts, and mature ookinetes, indicating that postzygotic development of P. vivax in A. dirus was asynchronous. The conversion efficiency of zygotes/ookinetes to oocysts varied among patients and was independent of zygote-ookinete density, suggesting that variations in host blood composition, e.g., antibodies, drugs, etc., may influence the success of zygote-ookinete development.     

Serotonin-storing cells of the chicken duodenum: light,fluorescence and electron microscopy,and immunohistochemistry

Summary In an attempt to identify duodenal endocrine cells emitting formaldehyde-induced fluorescence (FIF), chicken duodena were studied by combined fluorescence, ultrastructural, silver impregnation and immunohistochemical methods in the same or consecutive sections. Our results show that: (1) Almost all the cells emitting yellow fluorescence by both the Falck-Hillarp and the Furness methods exhibit an immunohistochemical reaction with serotonin (5-HT) antiserum. (2) Almost all cells radiating yellow fluorescence by the Furness method stain with toluidine blue in Epon-embedded sections but, by high-voltage electron microscopy, can be subdivided into two types of cell containing either small round or polymorphous types of granules. (3) In the sections from which resin had been removed, all the cells emitting yellow FIF show argentaffinity by the Singh method, but not all cells display argyrophilia with the Grimelius method. (4) Cells exhibiting both argyrophil and argentaffin reactions in deresined serial sections are also separated into two types of cell, containing either small spherical or polymorphous types of granules by conventional electron microscopy in thin sections. Therefore, chicken enterochromaffin cells emit yellow FIF, store 5-HT, show both argentaffinity and argyrophilia, but are ultrastructurally classified into two types of granule-containing cells which may be related to polypeptides coexisting with 5-HT.     

Species composition and nocturnal activity of phlebotomine sand flies (Diptera: Psychodidae) inhabiting a limestone cave in Thailand

We investigated the nocturnal activity of cave‐dwelling sand flies at different time intervals and determined their species composition and seasonal variation. Sand flies were captured on one night each month using CDC light traps from 18:00–06:00 with the collecting bag being changed every two h between February, 2010 and January, 2011. A total of 18,709 individuals, including 10,740 males and 7,969 females, was collected. The overall ratio between male and female specimens was 1:0.74. The collected specimens included 14 species from four genera, Chinius, Idiophlebotomus, Phlebotomus, and Sergentomyia. Sergentomyia phadangensis was the most abundant species (comprising 31.9% of the collected individuals), followed by Se. anodontis (22.8%) and Ph. mascomai (18.2%). The highest number of specimens was collected in July (15.6%), followed by May (15.5%) with the peak of collection recorded at the time interval of 00:01–02:00, followed by 22:01–00:00. However, there were no significant differences observed among time intervals of sand fly collections (p=0.154). Observations of the nocturnal activity of male and female sand flies throughout the night suggest that phlebotomine sand flies show the greatest activity level after midnight.     

Improving Environmental Sanitation, Health, and Well-Being: A Conceptual Framework for Integral Interventions

We introduce a conceptual framework for improving health and environmental sanitation in urban and peri-urban areas using an approach combining health, ecological, and socioeconomic and cultural assessments. The framework takes into account the three main components: i) health status, ii) physical environment, and iii) socioeconomic and cultural environment. Information on each of these three components can be obtained by using standard disciplinary methods and an innovative combination of these methods. In this way, analyses lead to extended characterization of health, ecological, and social risks while allowing the comprehensive identification of critical control points (CCPs) in relation to biomedical, epidemiological, ecological, and socioeconomic and cultural factors. The proposed concept complements the conventional CCP approach by including an actor perspective that considers vulnerability to risk and patterns of resilience. Interventions deriving from the comprehensive analysis consider biomedical, engineering, and social science perspectives, or a combination of them. By this way, the proposed framework jointly addresses health and environmental sanitation improvements, and recovery and reuse of natural resources. Moreover, interventions encompass not only technical solutions but also behavioral, social, and institutional changes which are derived from the identified resilience patterns. The interventions are assessed with regards to their potential to eliminate or reduce specific risk factors and vulnerability, enhance health status, and assure equity. The framework is conceptualized and validated for the context of urban and peri-urban settings in developing countries focusing on waste, such as excreta, wastewater, and solid waste, their influence on food quality, and their related pathogens, nutrients, and chemical pollutants.     

Sustained Release of Amoxicillin from Ethyl Cellulose-Coated Amoxicillin/Chitosan–Cyclodextrin-Based Tablets

Sustained release mucoadhesive amoxicillin tablets with tolerance to acid degradation in the stomach were studied. The sustained-release tablets of amoxicillin were prepared from amoxicillin coated with ethyl cellulose (EC) and then formulated into tablets using chitosan (CS) or a mixture of CS and beta-cyclodextrin (CD) as the retard polymer. The effects of various (w/w) ratios of EC/amoxicillin, the particle sized of EC coated amoxicillin and the different (w/w) ratios of CS/CD for the retard polymer, on the amoxicillin release profile were investigated. The physicochemical properties of the EC coated amoxicillin particles and tablets were determined by scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. The result showed that the release profiles of amoxicillin were greatly improved upon coating with EC, while the inclusion of CD to the CS retardant additionally prolonged the release of the drug slightly. Overall, a sustained release of amoxicillin was achieved using amoxicillin coated with EC at a (w/w) ratio of 1:1 and a particle size of 75–100 μm. Therefore, the tablet formulation of amoxicillin may be an advantageous alternative as an orally administered sustained-release formulation for the treatment of peptic ulcers.     

Development of Mannosylated Liposomes Using Synthesized N-Octadecyl-d-Mannopyranosylamine to Enhance Gastrointestinal Permeability for Protein Delivery

The lysozyme (LZ)-entrapped mannosylated liposomes were prepared in this study by the use of N-octadecyl-D-mannopyranosylamine (SAMAN), which had been synthesized in-house and confirmed by characterization with FTIR and NMR. The reactant residues of synthesized SAMAN were found to be less than 1%. The mean sizes, zeta potentials, drug entrapment efficiencies, and loading capacities of all liposomal formulations were in the ranges of 234.7 to 431.0 nm, -10.97 to -25.80 mV, 7.52 to 14.10%, and 1.44 to 2.77%, respectively. The permeability of mannosylated LZ liposomes across Caco-2 cell monolayers was significantly enhanced to about 2.5- and 7-folds over those of conventional liposomes and solution, respectively, which might be due to the role of mannose receptor or mannose-binding protein on the intestinal enterocytes.     

Typhoid Outbreak in Songkhla,Thailand 2009–2011: Clinical Outcomes,Susceptibility Patterns,and Reliability of Serology Tests

Objective

To determine the clinical manifestations and outcomes, the reliability of Salmonella enterica serotype Typhi (S ser. Typhi) IgM and IgG rapid tests, and the susceptibility patterns and the response to treatment during the 2009–2011 typhoid outbreak in Songkhla province in Thailand.

Method

The medical records of children aged <15 years with S ser. Typhi bacteremia were analysed. The efficacy of the typhoid IgM and IgG rapid tests and susceptibility of the S ser. Typhi to the current main antibiotics used for typhoid (amoxicillin, ampicillin, cefotaxime, ceftriaxone, co-trimoxazole, and ciprofloxacin), were evaluated.

Results

S ser. Typhi bacteremia was found in 368 patients, and all isolated strains were susceptible to all 6 antimicrobials tested. Most of the patients were treated with ciprofloxacin for 7–14 days. The median time (IQR) of fever before treatment and duration of fever after treatment were 5 (4, 7) days and 4 (3, 5) days, respectively. Complications of ascites, lower respiratory symptoms, anemia (Hct <30%), and ileal perforation were found in 7, 7, 22, and 1 patients, respectively. None of the patients had recurrent infection or died. The sensitivities of the typhoid IgM and IgG tests were 58.3% and 25.6% respectively, and specificities were 74.1% and 50.5%, respectively.

Conclusion

Most of the patients were diagnosed at an early stage and treated with a good outcome. All S ser. Typhi strains were susceptible to standard first line antibiotic typhoid treatment. The typhoid IgM and IgG rapid tests had low sensitivity and moderate specificity.