Lower doses of carvedilol in Japanese heart failure patients with reduced ejection fraction could show the potential to be non-inferior to higher doses in US patients: An international collaborative observational study.

The Japanese national guidelines recommend significantly lower doses of carvedilol for heart failure with reduced ejection fraction (HFrEF) management than the US guidelines. Using real-world data, we determined whether initial and target doses of carvedilol in Japanese patients (JPNs) differ from those in US patients (USPs), especially in Asian Americans (ASA) and Caucasians (CA), and investigated differences in outcomes. We collected data from the electronic medical records, including demographics, carvedilol dosing, tolerability, cardiac functional indicators like EF, cardiovascular events including all-cause deaths, and laboratory values from the University of California, San Diego Health and Osaka University.

Platelet reactivity testing in peripheral artery disease.

Purpose: Oral antiplatelet therapy is routinely used to prevent adverse cardiovascular events in patients with peripheral artery disease (PAD). Several laboratory tests are available to quantify the degree of platelet inhibition following antiplatelet therapy. This article aims to provide a review of the literature surrounding platelet functional testing in patients with PAD receiving oral P2Y12 inhibitors and to offer guidance to clinicians for the use and interpretation of these tests.

Successful Use of Cangrelor and Heparin for Cardiopulmonary Bypass in a Patient With Heparin-Induced Thrombocytopenia and End-Stage Renal Disease: A Case Report.

Heparin is the only well-established anticoagulant medication for cardiopulmonary bypass making selecting an alternative anticoagulant challenging in patients with heparin-induced thrombocytopenia. Other anticoagulant medications can cause significant postoperative bleeding, especially in patients with end-stage renal disease. We present a case of a 63-year-old woman requiring aortic valve replacement with a history of heparin-induced thrombocytopenia and end-stage renal disease.

Anticoagulant Use in High Stroke-Risk Patients With Nonvalvular Atrial Fibrillation.

Unlabelled: Background Oral anticoagulants (OACs) are recommended for nonvalvular atrial fibrillation (NVAF) patients with moderate-to high-stroke risk. Objective To examine nationally reflective OAC usage in incident NVAF patients longitudinally. Design Three-year retrospective cohort analysis.

A piecewise-focused high DQE detector for MV imaging.

Purpose: Electronic portal imagers (EPIDs) with high detective quantum efficiencies (DQEs) are sought to facilitate the use of the megavoltage (MV) radiotherapy treatment beam for image guidance. Potential advantages include high quality (treatment) beam's eye view imaging, and improved cone-beam computed tomography (CBCT) generating images with more accurate electron density maps with immunity to metal artifacts. One approach to increasing detector sensitivity is to couple a thick pixelated scintillator array to an active matrix flat panel imager (AMFPI) incorporating amorphous silicon thin film electronics.

Multidisciplinary initiative to improve inpatient anticoagulation and management of venous thromboembolism.

Purpose: The implementation of best practices to optimize inpatient anticoagulation and venous thromboembolism (VTE) management are described.

Summary: A multidisciplinary team of pharmacists, hospitalists, computer prescriber-order-entry system (CPOE) experts, and data specialists was assembled. A VTE management best-practices bundle was designed and implemented using education, CPOE upgrades, clinical decision support, triggered consultation, and checklists.

Induction of apoptosis in host cells: a survival mechanism for Leishmania parasites?

Leishmania parasites invade host macrophages, causing infections that are either limited to skin or spread to internal organs. In this study, 3 species causing cutaneous leishmaniasis, L. major, L.

Leishmanicidal activity of Yucatecan medicinal plants on Leishmania species responsible for cutaneous leishmaniasis.

The leishmanicidal activity of 15 extracts and 4 pure metabolites obtained from Urechites andrieuxii, Colubrina greggii, Dorstenia contrajerva, and Tridax procumbens was evaluated using the newly developed MTS ({3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay, optimized for promastigotes of Leishmania major, Leishmania tropica, and Leishmania aethiopica, as well as for L. aethiopica axenic amastigotes. The assay was then used for calculating the percentage of viable stationary phase parasites after a 24-hr treatment with each plant extract or pure metabolite.

Antibacterial activity of plants used in traditional medicines of Ghana with particular reference to MRSA.

Ethnopharmacological Relevance: : In an ethno botanical survey carried out in the Akwapim-North district of the Republic of Ghana, 25 plant species, used in traditional medicine to treat skin disease and/or to treat antimicrobial (viral, bacterial or protozoan) infections were identified.

Aim Of Study: : To investigate the antimicrobial activity of traditional Ghanaian medicines with special interest in anti-methicillin-resistant Staphylococcus aureus (MRSA) activity.

Materials And Methods: : Chloroform, ethanol and aqueous extracts (including use of a Stomacher) of these plants were prepared and agar-well diffusion tests, MIC's and MBC's were used to investigate antimicrobial activity.

The effect of cicerfuran, an arylbenzofuran from Cicer bijugum, and related benzofurans and stilbenes on Leishmania aethiopica, L. tropica and L. major.

The effect of 3 arylbenzofurans and 7 stilbenes on the growth of Leishmania parasites and human monocytes was evaluated. Promastigotes from cultures of L. aethiopica, L.

Synthesis and influenza virus sialidase inhibitory activity of analogues of 4-Guanidino-Neu5Ac2en (Zanamivir) modified in the glycerol side-chain.

Analogues of 4-Guanidino-Neu5Ac2en (Zanamivir) have been prepared containing carbamate substituents at the 7-hydroxy position. (4S,5R,6R)-5-Acetylamino-6-[1R-[(6-aminohexyl)carbamoyloxy]-2R,3-dihydroxypropyl]-4-guanidino-5,6-dihydro-4H-pyran-2carboxylic acid and (4S,5R,6R)-5-Acetylamino-6-[1R-[heptylcarbamoyloxy]-2R,3-dihydroxypropyl]-4-guanidino-5,6-dihydro4H-pyran2-carboxylic acid were the two analogues possessing activity comparable to Zanamivir, showing potent inhibition of influenza virus sialidases and good antiviral activity in vitro.

Acute and Chronic Pulmonary Emboli.

Under most circumstances, the goal of treatment of pulmonary embolism is the prevention of recurrent embolic events, achieved through conventional anticoagulant therapy with unfractionated heparin or a low molecular weight heparin, followed by warfarin therapy for a minimum of 6 months. When acute pulmonary embolism is associated with significant right ventricular dysfunction or systemic hypotension, more aggressive intervention may be warranted. Under these circumstances, potential interventions include thrombolytic therapy (either systemic or catheter-directed), placement of an inferior vena caval filter, catheter-based embolectomy, or surgical embolectomy.

Inhibition of eosinophil rolling and recruitment in P-selectin- and intracellular adhesion molecule-1-deficient mice.

To determine the relative in vivo importance of endothelial expressed adhesion molecules to eosinophil rolling, adhesion, and transmigration, we have induced eosinophilic peritonitis using ragweed allergen in P-selectin-deficient, intracellular adhesion molecule-1 (ICAM-1)-deficient and control wild-type mice. Circulating leukocytes visualized by intravital microscopy exhibited reduced rolling and firm adhesion in P-selectin-deficient mice and reduced firm adhesion in ICAM-1-deficient mice. Eosinophils exhibited reduced rolling and firm adhesion to endothelium in P-selectin-deficient mice.

Benzophenone derivatives: a novel series of potent and selective inhibitors of human immunodeficiency virus type 1 reverse transcriptase.

A series of benzophenone derivatives has been synthesized and evaluated as inhibitors of HIV-1 reverse transcriptase (RT) and the growth of HIV-1 in MT-4 cells. Through the use of the structure-activity relationships within this series of compounds and computational chemistry techniques, a binding conformation is proposed. The SAR also indicated that the major interactions of 1h with the RT enzyme are through hydrogen bonding of the amide and benzophenone carbonyls and pi-orbital interactions with the benzophenone nucleus and an aromatic function separated from the benzophenone by a suitable spacer group.

Discovery and analysis of a series of C2-symmetric HIV-1 proteinase inhibitors derived from penicillin.

In order to identify a suitable peptide substrate for human immunodeficiency virus-1 (HIV-1) proteinase, a range of peptides from various cleavage sites within the gag-pol polyprotein were assayed by HPLC for specific cleavage. The peptide with the optimal combination of favorable kinetics and good solubility was based on the N-terminus cleavage site of HIV-1 proteinase (KQGTVSFNF*PQIT). The HPLC assay, using the above peptide, was developed into a rapid isocratic method in order to analyze inhibition kinetics.

A series of penicillin derived C2-symmetric inhibitors of HIV-1 proteinase: synthesis, mode of interaction, and structure-activity relationships.

The C2-symmetric diester 1 was identified by random screening as a novel inhibitor of HIV-1 proteinase. This led to the preparation of a series of related more potent amides from readily accessible penicillins. Many of the compounds showed potent antiviral activity in HIV-1-infected MT-4 cells and an ability to inhibit syncytia formation in infected C8166 cells, with no evidence of cytotoxicity.

Cutaneous leishmaniasis in south-western Ethiopia: Ocholo revisited.

The borough of Ocholo, on the western side of the Ethiopian Rift Valley, is an endemic focus for Leishmania aethiopica infection and has been surveyed thrice between 1987 and 1990. In 1989, 3022 inhabitants (> 95% of the population) were interviewed and examined. The overall prevalence of localized cutaneous leishmaniasis (LCL) was 3.

Leishmania aethiopica: infections in laboratory animals.

Leishmania aethiopica parasites were inoculated into 11 different strains and species of small laboratory animals. Clinical lesions were only produced following inoculation of hamster noses and thus this parasite is highly selective in both species and site for the laboratory animals tested. Parasites could, however, be recovered from draining lymph nodes 3 weeks after infection of BALB/c mice.

Expression of atrial natriuretic factor as a cleavable fusion protein with chloramphenicol acetyltransferase in Escherichia coli.

Recombinant fusion proteins containing human atrial natriuretic factor, ANF(1-28) joined to chloramphenicol acetyltransferase (CAT) via cleavable linker sequences have been produced in Escherichia coli. The linker sequences were designed to allow the release of authentic ANF(1-28) following proteolytic cleavage by enterokinase or thrombin, or chemical cleavage with 2-(2-nitrophenylsulphenyl)-3-methyl-3'-bromoindolenine. Proteins, containing ANF(1-28) fused to the carboxyl-terminal region of CAT (using the ScaI restriction site in the cat gene), were largely soluble in E.

Viability of Mycobacterium leprae: a comparison of morphological index and fluorescent staining techniques in slit-skin smears and M. leprae suspensions.

In a comparison of the estimation of Mycobacterium leprae viability by morphology and the fluorescent vital dyes FDA/EB and R123/EB, the latter techniques were more satisfactory using suspensions and slit-skin smears of M. leprae bacilli. Both FDA/EB and R123/EB seem to more accurately reflect viability after freeze/thaw cycles and heating, and are able to detect lower percentages of viable bacilli.