Preparation and nucleophilic substitution of the 2,4,6-triphenylpyridinium salts, diazonium intermediates and N,N-1,2-benzenedisulfonylimides of chiral amino acids

Three methods for preparation of D-amino acids by nucleophilic substitution on derivatives of their L-antipodes have been attempted. Nucleophilic substitution on optically active phenylalanine ethyl ester triphenylpyridinium salt yielded partial inverted azide products. The N,N-disulfonylimide intermediate of the same ester was synthesized in high yield and optical purity, but the substitution reaction on this compound was not achieved. Diazotization of amino acid ammonium chlorides and tosylates in solution of sodium azide in aprotic solvents gave optically active chloro and tosyl compounds instead of the intended azide products. Alternative methods to circumvent the problem of the competing ammonium salt counterions duringdiazotization reactions have been suggested

Matched ligands for small, stable colloidal nanoparticles of copper, cuprous oxide and cuprous sulfide

This work applies organometallic routes to copper(0/I) nanoparticles and describes how to match ligand chemistries with different material compositions. The syntheses involve reacting an organo-copper precursor, mesitylcopper(I) [CuMes]z (z=4, 5), at low temperatures and in organic solvents, with hydrogen, air or hydrogen sulfide to deliver Cu, Cu2 O or Cu2 S nanoparticles. Use of sub-stoichiometric quantities of protonated ligand (pro-ligand; 0.1-0.2 equivalents vs. [CuMes]z ) allows saturation of surface coordination sites but avoids excess pro-ligand contaminating the nanoparticle solutions. The pro-ligands are nonanoic acid (HO2 CR1 ), 2-[2-(2-methoxyethoxy)ethoxy]acetic acid (HO2 CR2 ) or di(thio)nonanoic acid, (HS2 CR1 ), and are matched to the metallic, oxide or sulfide nanoparticles. Ligand exchange reactions reveal that copper(0) nanoparticles may be coordinated by carboxylate or di(thio)carboxylate ligands, but Cu2 O is preferentially coordinated by carboxylate ligands and Cu2 S by di(thio)carboxylate ligands. This work highlights the opportunities for organometallic routes to well-defined nanoparticles and the need for appropriate ligand selection

Matched Ligands for Small, Stable Colloidal Nanoparticles of Copper, Cuprous Oxide and Cuprous Sulfide

This work applies organometallic routes to copper(0/I) nanoparticles and describes how to match ligand chemistries with different material compositions. The syntheses involve reacting an organo-copper precursor, mesitylcopper(I) [CuMes]z (z=4, 5), at low temperatures and in organic solvents, with hydrogen, air or hydrogen sulfide to deliver Cu, Cu2O or Cu2S nanoparticles. Use of sub-stoichiometric quantities of protonated ligand (pro-ligand; 0.1–0.2 equivalents vs. [CuMes]z) allows saturation of surface coordination sites but avoids excess pro-ligand contaminating the nanoparticle solutions. The pro-ligands are nonanoic acid (HO2CR1), 2-[2-(2-methoxyethoxy)ethoxy]acetic acid (HO2CR2) or di(thio)nonanoic acid, (HS2CR1), and are matched to the metallic, oxide or sulfide nanoparticles. Ligand exchange reactions reveal that copper(0) nanoparticles may be coordinated by carboxylate or di(thio)carboxylate ligands, but Cu2O is preferentially coordinated by carboxylate ligands and Cu2S by di(thio)carboxylate ligands. This work highlights the opportunities for organometallic routes to well-defined nanoparticles and the need for appropriate ligand selection

Coronary artery fistula; coronary computed topography – The diagnostic modality of choice

Coronary artery fistulae (CAF) are rare anomalies. They are vascular communications between the coronary arteries and other cardiac structures, either cardiac chambers or great vessels. There can be considerable variation in the course of a coronary artery fistula. We report a case of a coronary artery fistula between the left circumflex coronary artery and the right and left atria. CAF are often diagnosed by coronary angiogram, however with the advent of new technologies such as Coronary Computed Tomography Angiography (Coronary CTA) the course and communications of these fistulae can be delineated non-invasively and with greater accuracy

Maternal and early life nutrition and physical activity: setting the research and intervention agenda for addressing the double burden of malnutrition in South African children.

Early life is important for later health outcomes, yet there are few studies which adequately address all of the potential early life insults that may affect later life health and growth trajectories. This is particularly evident in low- to middle-income countries such as South Africa, where women of childbearing age are particularly vulnerable to high levels of physical inactivity, malnutrition, and obesity. Pregnancy may therefore be an opportune time to change behaviours and improve maternal and offspring health outcomes, and decrease the inter-generational transfer of risk. We show clear evidence that physical activity and nutrition are important target areas for intervention during pregnancy and in the early years of life, yet that current literature in Africa, and specifically South Africa, is limited. We have outlined the available literature concerning the impact of maternal and early life nutrition and physical activity on the health status of South African children, and have provided some recommendations for future research and policy

Molecular Detection of Leishmania spp. in Skin and Blood of Stray Dogs from Endemic Areas of Cutaneous Leishmaniasis in Saudi Arabia

Dogs can act as reservoirs of canine leishmaniasis, caused by Leishmania species. The aims of this study were to determine the prevalence of canine leishmaniasis using a PCR technique among stray dogs living in three provinces of Saudi Arabia, Riyadh, Al-Ahsa Oasis and Al-Qaseem, here the disease is endemic; and to identify and document different Leishmania to species levels Methods: This cross-sectional investigation was conducted, from Mar 2016 to Apr 2018, in three parts of Saudi Arabia: Central province (Riyadh), Eastern province (Al-Ahsa Oasis) and Al-Qaseem province. Blood samples were collected from 526 dogs; 40 presented cutaneous nodules so were suspected clinically of cutaneous leishmaniasis. Biopsy tissue collections and parasite cultures were performed. A generic kDNA was performed using different primers for Leishmania differentiation. Results: All blood samples were negative for Leishmania infantum infection by molecular analysis, though forty dogs had thick cutaneous lesions in different parts of their body. Four dogs’ skin lesions were associated with dermatitis, splenomegaly and lymphadenomegaly. Parasite culture was used to diagnose cutaneous leishmaniasis, identifying 31/40 (77.5%) positive samples. Overall, of 526 samples, the prevalence of L. major and L. tropica was found to be 4% and 1.9%, respectively. Gender and age had a significant effect on Leishmania prevalence: (P=0.0212 and0.0357), respectively. Conclusion: This was the first molecular study of dog leishmaniasis from Saudi Arabia of dogs confirmed to have cutaneous leishmaniasis. Further epidemiological and molecular investigations of domestic and wild canine infections with L. major, L. tropica and L. infantum in endemic and nonendemic areas of Saudi Arabia are required, for leishmaniasis control

Effect of alogliptin on hypertensive chronic kidney disease patients with type 2 diabetes mellitus

BackgroundDiabetes mellitus (DM) is a leading cause of chronic kidney disease (CKD). The antihyperglycemic treatment options for patients with Type 2 DM are limited because of safety and tolerability concerns.AimsTo retrospectively assess the effect of using Alogliptin; a dipeptidyl peptidase-4 inhibitor (DPP-4i) along with conventional gliclazide: a sulphonylurea (SU) on renal outcomes and glycaemic control in T2DM patients with mild CKD and hypertension.MethodsA total of 76 patient records (38 males and 38 females) of patient ages 40–60 were analysed from the kidney unit at Punjab Care hospital, Lahore, Pakistan. All patients had a confirmed history of T2DM with mild CKD and established hypertension.Eligible patients were divided into two groups of 38 individuals each. Group SU received gliclazide monotherapy (SU) or Alogliptin (DPP-4i)+gliclazide (SU) add on therapy. All patients were followed up for 12 months.ResultsThe alogliptin (DPP-4i) plus gliclazide (SU) add on therapy group, in comparison to the group only receiving gliclazide (SU), showed a significant difference in eGFR values. The mean±SD GFR values post 12 months were 74.8±0.31 (95%CI:74.8±0.09;74.7–74.9) and 76.1±0.25 (95%CI: 76.1±0.08;76.0-76.2) for SU vs. SU+DPP-4i, respectively, with mean calculated effect size of 1.6,. HbA1c, 1,5 AG and ipid profile values have significantly changed (

YK-4-279 Inhibits ERG and ETV1 Mediated Prostate Cancer Cell Invasion

Background: Genomic rearrangements involving the ETS family of transcription factors occur in 40–70 % of prostate cancer cases. ERG and ETV1 are the most common ETS members observed in these genetic alterations. The high prevalence of these rearrangements and their biological significance represents a novel therapeutic target for the treatment of prostate cancer. Methods and Findings: We recently reported the development of YK-4-279, a small molecule inhibitor of EWS-FLI1 oncoprotein in Ewing’s Sarcoma. Since ERG and ETV1 belong to the same class of ETS factors as FLI1, we tested the ability of YK-4-279 to inhibit biological functions of ERG and ETV1 proteins in prostate cancer. YK-4-279 inhibited ERG and ETV1 mediated transcriptional activity in a luciferase assay. YK-4-279 also decreased ERG and ETV1 downstream target mRNA and protein expression in ETV1-fusion positive LNCaP and ERG fusion positive VCaP cells. YK-4-279 reduced the motility of LNCaP cells in a scratch assay and the invasive phenotype of both LNCaP and VCaP cells in a HUVEC invasion assay. Fusion-negative PC3 cells were unresponsive to YK-4-279. SiRNA mediated ERG knockdown in VCaP cells resulted in a loss of drug responsiveness. Concurrently, transient ERG expression in PC-3 cells resulted in increased invasive potential, which was reduced by YK-4-279. Conclusion: These data demonstrate that YK-4-279 inhibits ERG and ETV1 biological activity in fusion-positive prostat