Precise Persuasion: Investigating Incentive Appeals for the Promotion of Antibiotic Stewardship with Message-induced Transitions.

Two different lines of research-interpersonal resistance and public campaign design-lead us to consider the use of incentive appeals to motivate behavior change, with a call for greater attention to and use of positive incentives. This study tests the potential to promote antibiotic stewardship through microbiome benefits. In addition, multiple analyses were used: A causal analysis allowed us to identify what moved (e.g., which beliefs and intentions), a latent transition analysis allowed us to reveal who moved (targets, nontargets, or both), and a Markov model allowed us to estimate the stable state of these moves or, in other words, where and how the repetition of the messages would ultimately lead in terms of transitions from state to state. An experiment (N = 298), grounded in the context of antibiotic stewardship, showed that incentive appeals moved people with problematic patterns of past behavior (categorized as Persuaders, Stockers, and Dissenters) to positive patterns of behavioral intentions (categorized as Stewards). The causal analysis, latent class analysis, and equilibrium values for the separate transition matrices showed the relative benefit for a message that highlighted the health and wellness benefits of the microbiome. Implications for persuasion theory and practice are discussed.

Silymarin in Combination with Vitamin C, Vitamin E, Coenzyme Q10 and Selenomethionine to Improve Liver Enzymes and Blood Lipid Profile in NAFLD Patients.

Background and Objectives: Non-Alcoholic Fatty Liver Disease (NAFLD) is an emerging cause of hepatopathy that is showing an increasing trend and where the recommendations of lifestyle modification are often not sufficient. The aim of this study is to evaluate the efficacy and tolerability profile of the association of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine (Medronys epato®) by analyzing liver enzymes, along with the lipidic profile, as markers of liver function, and ultrasound results in NAFLD patients. Materials and Methods: This study enrolled 81 patients with mild to severe NAFLD, divided into two groups: Group A (N = 41) received two capsules a day of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine (Medronys epato®), and Group B (N = 40) received only recommendations for lifestyle modification including hypocaloric diet, physical exercise and encouragement for weight loss. Patients have been evaluated at three timepoints: baseline (T0), after 45 days of treatment (T1) and after 90 days of treatment (T2), by collecting blood parameters of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and the lipid blood profile. Ultrasonographic results have been analyzed at T0 and T2, along with the tolerability profile and side effects, registered at time T2. Results: The administration of the association of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine (Medronys epato®) was effective since it showed a significant reduction of the evaluated parameters of ALT, AST, ALP and GGT, a significant improvement of lipid parameters, evaluated as markers of liver function, and improvements of ultrasonographic results. The use of this formulation at the dosage of two capsules a day has been well tolerated and no adverse events have been reported during study period of three months. Conclusions: The administration of the association of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine (Medronys epato®) was effective and well tolerated in the improvement of hepatic function of NAFLD patients.

Antifungal cyclic lipopeptides from Bacillus amyloliquefaciens strain BO5A.

A bioassay-guided fractionation of Bacillus amyloliquefaciens strain BO5A afforded the isolation of two new cyclic lipopeptides (1 and 2) as the major lipid constituents (>60%) of the CHCl3-MeOH (2:1) extract. The chemical structures of the isolated metabolites were elucidated by spectroscopic methods, including 1D and 2D NMR spectroscopy, mass spectrometry (MS), secondary ion mass spectrometry (MS1, MS2), and chemical degradation. The compounds are members of the surfactins family and are based on a heptapeptide chain composed by Glu-Val-Leu-Val-Asp-Leu-Leu. Its N-terminal end is N-acylated by an (R)-3-hydroxy fatty acid with linear alkyl chains of 16:0 and 15:0 (1 and 2, respectively). The 3-hydroxyl group closes a 25-membered lactone ring with the carboxylic group of the C-terminal amino acid. The isolated compounds were tested for their inhibitory activity against the four pathogenic fungi Fusarium oxysporum, Aspergillus niger, Botrytis cinerea, and Penicillium italicum and the biocontrol fungus Trichoderma harzianum. Compound 2 displayed activity against all tested pathogens.

Inverse virtual screening of antitumor targets: pilot study on a small database of natural bioactive compounds.

An inverse virtual screening in silico approach has been applied to natural bioactive molecules to screen their efficacy against proteins involved in cancer processes, with the aim of directing future experimental assays. Docking studies were performed on a panel of 126 protein targets extracted from the Protein Data Bank, to analyze their possible interactions with a small library of 43 bioactive compounds. Analysis of the molecular docking results was performed through the use of tables containing energy data organized in a matrix. The application of this approach may facilitate the prediction of the activity of unknown ligands for known targets involved in the development of cancer and could be applied to other models based on different libraries of ligands and different panels of targets.

Antifungal lipopeptides from Bacillus amyloliquefaciens strain BO7.

Three new lipopeptides (1-3) were isolated from the organic extract of Bacillus amyloliquefaciens strain (BO7). These compounds represented the major constituents (>60%) of the total cell lipids extractable with CHCl(3)/MeOH (2:1). Elucidation of their chemical structure was carried out by spectroscopic analyses, including 1D and 2D NMR spectroscopy, mass spectrometry (MS), and secondary ion mass spectrometry (MS/MS), along with chemical degradation. The compounds are members of the surfactins family and are based on the heptapeptide Glu-Leu-Leu-Ala-Asp-Leu-Leu, N-acylated to the N-terminal by an (R)-3-hydroxy fatty acid with linear alkyl chains from 16:0 to 18:0 (1-3, respectively). An ester bond between the 3-hydroxyl group of the fatty acid and the carboxylic group of the C-terminal amino acid closes a 13-membered lactone ring. The bacterial lipopeptides, particularly compound 3, displayed strong and dose-dependent antifungal activity against the plant pathogenic fungus Fusarium oxysporum.

The Role of EGCG in Breast Cancer Prevention and Therapy.

BACKGROUND: Breast cancer is the most frequent cancer in women. Green tea has been studied for breast cancer chemopreventive and possibly chemotherapeutic effects due to its high content in polyphenolic compounds, including epigallocatechin-3-gallate (EGCG). METHOD: This review is based on literature research that included papers registered on the Medline® database. The research was conducted through PubMed, applying the following query: "EGCG"AND "breast cancer". The result was a total of 88 articles in which this review stands on. RESULTS: In vitro, EGCG shows antioxidant or pro-oxidant properties, depending on the concentration and exposure time. EGCG blocks cell cycle progression and modulates signaling pathways that affect cell proliferation and differentiation. EGCG also induces apoptosis, negatively modulates different steps involved in metastasis, and targets angiogenesis by inhibiting VEGF transcription. In vivo investigations have shown that oral administration of EGCG results in the reduction of tumor growth and in antimetastatic and antiangiogenic effects in animal xenograft and allograft models. DISCUSSION: Much remains unknown about the molecular mechanisms involved in the protective effects of EGCG on mammary carcinogenesis. In addition, more studies in vivo are necessary to determine the potential toxicity of EGCG at higher doses and to elucidate its interactions with other drugs. CONCLUSION: A protective effect of EGCG has been shown in different experimental models and under different experimental conditions, suggesting clinical implications of EGCG for breast cancer prevention and therapy. The data presented in this review support the importance of further investigations.

Insight into the mechanism of action of plakortins, simple 1,2-dioxane antimalarials.

A multidisciplinary approach, based on molecular dynamics/mechanics, ab initio calculations, dynamic docking studies, and chemical reactions, has been employed to gain insight into the mechanism of the antimalarial action of plakortin and dihydroplakortin, simple 1,2-dioxanes isolated from the sponge Plakortis simplex. Our results show that these molecules, after interaction of the endoperoxide bond with Fe(ii), likely coming from the heme molecule, give rise to the formation of an oxygen radical, followed by rearrangement to give a carbon radical centered on the "western" alkyl side-chain. The carbon radicals generated on the side-chain, amenable for intermolecular reactions, should represent the toxic intermediates responsible for subsequent reactions leading to plasmodium death. The minimal structural requirements necessary for the activity of this class of antimalarial agents have been identified and discussed throughout the paper.

Manadoperoxides A-D from the Indonesian sponge Plakortis cfr. simplex. Further insights on the structure-activity relationships of simple 1,2-dioxane antimalarials.

The new endoperoxyketal polyketides manadoperoxides A-D (2-5) have been isolated from the Indonesian sponge Plakortis cfr. simplex and their stereostructures established by means of spectroscopic data and semisynthetic transformations. Manadoperoxides were assayed in vitro against D10 and W2 strains of Plasmodium falciparum and showed moderate antimalarial activity compared to that of plakortin (1) and peroxyplakoric B(3) ester (9), the latter differing from manadoperoxide B only by minor structural details. This unexpected difference in the antimalarial activity has been rationalized on the basis of our recently published model for the interaction of 1,2-dioxanes with heme and production of C-centered radicals toxic to the parasite. For the manadoperoxides, either the endoperoxide linkage is inaccessible to the heme iron or the O1 radical cannot evolve to produce a C-centered radical.

Genepolide, a sesterpene gamma-lactone with a novel carbon skeleton from mountain wormwood (Artemisia umbelliformis).

The sesterpene gamma-lactone genepolide (5) has been isolated from a Swiss horticultural variety of mountain wormwood (Artemisia umbelliformis) developed as a thujones-free alternative to native Western Alps wormwoods for the production of liqueurs. Genepolide is the formal Diels-Alder adduct of the exomethylene-gamma-lactone costunolide (2) and the diene myrcene (6), two poorly reactive partners in cycloaddition reactions, and its structure was elucidated through a combination of spectroscopic methods. An investigation on the thermal stability of mixtures of 2 and 6, as well as considerations on the sensitivity of 2 to Brønsted and Lewis acids, suggests that 5 is a genuine natural product and that the Swiss chemotype of A. umbelliformis contains Diels-Alderase enzymatic activity that is lacking in native mountain wormwoods from Western Alps. Remarkable differences in thermal and acid-catalyzed reactions of the cyclodecadiene moiety of 2 and 5 suggest that quaternarization at C-11 has far-reaching effects on the reactivity of their homoconjugated medium-sized diene system. The wide occurrence of this structural motif in sesquiterpenoids makes this issue worth a systematic investigation.

Polyacetylenes from sardinian Oenanthe fistulosa: a molecular clue to risus sardonicus.

An investigation of Oenanthe fistulosa from Sardinia afforded oenanthotoxin (1a) and dihydrooenanthotoxin (1b) from the roots and the diacetylenic epoxydiol 2 from the seeds. The absolute configuration of 1a and 1b was established as R by the modified Mosher's method, and the structure of 2 by chemical correlation with (+)-(3R,8S)-falcarindiol. Oenanthotoxin (1a) and dihydrooenanthotoxin (1b) were found to potently block GABAergic responses, providing a molecular rationale for the symptoms of poisoning from water-dropwort (Oenanthe crocata) and related plants. These observations bear relevance for a series of historical and ethnopharmacological observations on the identification of the Sardonic herb and the molecular details of the facial muscular contraction caused by its ingestion (risus sardonicus).

Stereostructure assignment of medium-sized rings through an NMR-computational combined approach. Application to the new germacranes ketopelenolides C and D.

The new germacrane derivatives ketopelenolides C and D have been isolated from great mugwort (Artemisia arborescens). Their stereostructure elucidation exemplifies some of the most common pitfalls facing the configurational assignment of medium-sized polyfunctionalized compounds. It was established through a combined strategy including chemical derivatization, NMR data analysis, molecular modeling, and quantum-mechanical calculations including a comparison between experimental 13C NMR data and a Boltzmann-weighted average of DFT-calculated 13C NMR chemical shifts.

Simplexidine, a 4-alkylpyridinium alkaloid from the Caribbean sponge Plakortis simplex.

Chemical analysis of the secondary metabolites of the Caribbean sponge Plakortis simplex, a source of many bioactive compounds, showed the presence of the new metabolite simplexidine (4), belonging to the extremely rare class of 4-alkyl-pyridinium alkaloids. The structural characterization of this molecule, based on spectroscopic methods, is reported.

[Therapeutics of infection by Helicobacter pylori in 2008]. / Terapéutica de la infección por Helicobacter pylori en el 2008.

Eradication therapy for Helicobacter pylori is recommended in a number of clinical conditions as developed in Maastricht Consensus (I, II, III). In this state of art we discuss the results of current eradication therapies, the new approaches to the management of infection (new antibiotics and eradication schemes) and antimicrobial resistance.

Artarborol, a nor-caryophyllane sesquiterpene alcohol from Artemisia arborescens. stereostructure assignment through concurrence of NMR data and computational analysis.

A nor-caryophyllane derivative, artarborol, has been isolated from wormwood (Artemisia arborescens) and its stereostructure established by using a combination of chemical derivatization, NMR data, molecular modeling, and quantum-mechanical calculations. In particular, comparison of experimental 13C NMR data with a Boltzmann-weighed average of 13C NMR chemical shifts, calculated by ab initio DFT method, supported the stereochemical assignment.

Endoperoxide derivatives from marine organisms: 1,2-dioxanes of the plakortin family as novel antimalarial agents.

Plakortin (1) is a remarkably simple 1,2-dioxane derivative, extracted from the marine sponge Plakortis simplex, showing a submicromolar activity against chloroquine-resistant strains of Plasmodium falciparum. Using plakortin as a novel antimalarial hit, we have prepared a series of semisynthetic derivatives in order to gain insights into the structural requirements of simple 1,2-dioxanes for exhibiting antimalarial activity. Their synthesis, spectroscopic and computational analysis, and in vitro antimalarial activity are herein reported. Results obtained, besides confirming the crucial role of the cycloperoxide functionality, revealed other structural features critical for antimalarial activity, namely the "Western" alkyl side chain, the dioxane ring conformation, and the absolute configuration of the stereogenic carbons on the 1,2-dioxane ring, when affecting the bioactive ring conformation.

Antifungal saponins from bulbs of white onion, Allium cepa L.

Three saponins, named ceposide A, ceposide B, and ceposide C were isolated from the bulbs of white onion, Allium cepa L. Elucidation of their structure was carried out by comprehensive spectroscopic analyses, including 2D NMR spectroscopy and mass spectrometry, and chemical evidences. The structures of the compounds were identified as (25R)-furost-5(6)-en-1ß,3ß,22α,26-tetraol 1-O-ß-D-xylopyranosyl 26-O-α-D-rhamnoyranosyl-(1→2)-O-ß-D-galactopyranoside (ceposide A), (25R)-furost-5(6)-en-1ß,3ß,22α,26-tetraol 1-O-ß-D-xylopyranosyl 26-O-α-D-rhamnoyranosyl-(1→2)-O-ß-D-glucopyranoside (ceposide B), and (25R)-furost-5(6)-en-1ß,3ß,22α,26-tetraol 1-O-ß-D-galactopyranosyl 26-O-α-D-rhamnoyranosyl-(1→2)-O-ß-D-galactopyranoside (ceposide C). The isolated compounds, alone and in combinations, were evaluated for their antimicrobial activity on ten fungal species. Antifungal activity of all three saponins increased with their concentration and varied with the following rank: ceposide B>ceposide A-ceposide C. We found a significant synergism in the antifungal activity of the three ceposides against Botrytis cinerea and Trichoderma atroviride, because growth of these fungi was strongly inhibited when the three saponins were applied in combination. In contrast, Fusarium oxysporum f. sp. lycopersici, Sclerotium cepivorum and Rhizoctonia solani were very little affected by saponins.

Structural characterization of tetranortriterpenes from Pseudrocedrela kotschyi and Trichilia emetica and study of their activity towards the chaperone Hsp90.

Investigation of roots extracts Pseudrocedrela kotschyi and Trichilia emetica led to identification of 5 limonoid derivatives, Kotschyins D-H, and 11 known compounds. Their structures were elucidated by extensive 1D and 2D NMR experiments in conjunction with mass spectrometry. A surface plasmon resonance (SPR) approach was adopted to screen their Hsp90 binding capability and kotschyin D showed a significant affinity for the chaperone. Therefore, the characterization of the biological activity of kotschyin D by means of a panel of chemical and biological approaches, including limited proteolysis, molecular docking and biochemical and cellular assays, was performed. Our result indicated this compound as a type of client selective Hsp90 inhibitor, directly binding to the middle domain of the protein and possibly preventing its interaction with the activator of Hsp90 ATPase 1 (Aha1).

Dispepsia funcional. Utilidad de las drogas procinéticas en su tratamiento en el año 2008 / Functional dyspepsia: Prokinetic drugs utility in your treatment in year 2008

En pacientes con dispepsia funcional pueden demostrarse anormalidades motoras en aproximadamente el 30-45 por ciento de los casos. Pacientes con retardo en el vaciado gástrico, electrogastrografía anormal (disritmias gástricas), alteraciones en la acomodación fúndica o distensión antral, podrían tener mejor respuesta a la terapéutica con drogas procinéticas que aquellos con vaciamiento gástrico normal. En este trabajo nosotros evaluamos nuevos agentes con targets específicos sobre anormalidades motoras especialmente agentes procinéticos. Los agentes procinéticos incluidos son: agentes antidopaminérgicos D1-D2; agonistas de receptores 5HT1-5HT3-5HT4; agonistas de receptores a la motilina y agentes opioides.

Experiencia en pacientes con serología positiva para el virus de inmunodeficiencia humana (H.I.V.) en la Unidad de Clínica Médica del Hospital Vélez Sársfield / Experience in patients with human immunodeficiency virus (H.I.V.) positive serology in the medical clinic unit to Vélez Sársfield Hospital

Se presenta la experiencia en la atención de pacientes con serología positiva para el HIV en una Unidad de Clínica Médica de un Hospital de Buenos Aires. Fueron internados 38 pacientes que registraron un total de 63 internaciones en un período de 4 años. El primer caso se presentó en 1990. El 92,1 por ciento eran varones y el 7,9 por ciento mujeres (p<0,01). La edad promedio fue de 30,2ñ 7,1 años. Entre los factores de riesgo prevalecieron la drogadicción endovenosa (72 por ciento), la heterosexualidad promiscua (66 por ciento) y la homosexualidad (34 por ciento). Parte de la población estudiada provenía de la Unidad Penitenciaria 2 (Villa Devoto), en quienes se halló una tríada de riesgo característica: homosexualidad, drogadicción endovenosa y tatuajes múltiples. Las manifestaciones al ingreso fueron poliadenomegalias (66 por ciento), síndrome de vías respiratorias (50 por ciento) y síndrome de impregnación (42 por ciento). El laboratorio de ingreso mostró anemia en el 55 por ciento de los casos, leucopenia en el 45 por ciento y plaquetopenia en el 39 por ciento. La evolución de la enfermedad estuvo relacionada con la presencia de una o más enfermedades. En nuestro medio predominaron las neumonías a Pneumocystis carinii (34 por ciento), tuberculosis (26 por ciento) y hepatitis viral C (26 por ciento). La mortalidad durante el período de internación fue del 15 por ciento (6 casos). La misma se debió a la falta de respuesta al tratamiento instituido y a la concurrencia, en todos los casos, de dos o más enfermedades en forma simultánea.