Application of neutral iridium(I) N-heterocyclic carbene complexes in ortho-directed hydrogen isotope exchange.

Bench-stable complexes of the type [Ir(COD)(NHC)Cl] (NHC = N-heterocyclic carbene) have been investigated within the field of hydrogen isotope exchange. By employing a sterically encumbered NHC within such complexes and catalyst loadings of only 5 mol%, moderate to high deuterium incorporations were achieved across a range of aromatic ketones and nitrogen-based heterocycles. The simple and synthetically accessible catalysts reported herein present alternatives to phosphine-based species and increase the available labelling systems with respect to established iridium-based isotope exchange methodologies.

Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with aminoindane and phenylpyrrolidine P4 motifs.

The rational design, syntheses and evaluation of potent sulfonamidopyrrolidin-2-one-based factor Xa inhibitors incorporating aminoindane and phenylpyrrolidine P4 motifs are described. These series delivered highly potent anticoagulant compounds with excellent oral pharmacokinetic profiles; however, significant time dependant P450 inhibition was an issue for the aminoindane series, but this was not observed with the phenylpyrrolidine motif, which produced candidate quality molecules with potential for once-daily oral dosing in humans.

The discovery of potent and long-acting oral factor Xa inhibitors with tetrahydroisoquinoline and benzazepine P4 motifs.

The discovery and evaluation of potent and long-acting oral sulfonamidopyrrolidin-2-one factor Xa inhibitors with tetrahydroisoquinoline and benzazepine P4 motifs are described. Unexpected selectivity issues versus tissue plasminogen activator in the former series were addressed in the later, delivering a robust candidate for progression towards clinical studies.

Probiotic yogurt consumption is associated with an increase of CD4 count among people living with HIV/AIDS.

AIM: To evaluate the long term effect of yogurt supplemented with Lactobacillus rhamnosus Fiti on the immune function (CD4 count) of people living with HIV/AIDS. BACKGROUND: Gastrointestinal infections and the leakage of microbial products from the gut have a profound impact on the deterioration of the immune system among people living with HIV/AIDS. Among persons not infected with the virus, probiotics can prevent gastrointestinal infections and restore an effective gut barrier, suggesting they might have a beneficial effect on the immune function of people living with HIV/AIDS. STUDY: We carried out an observational retrospective study over a period of 3 years, with longitudinal comparison of the CD4 count within participants (n=68) before and during probiotic yogurt consumption, and compared with a control group of participants not consuming the yogurt (n=82). RESULTS: Among the yogurt consumers before use and the nonconsumers, an average increase in CD4 count was seen of 0.13 cells/µL/day (95% CI; 0.07-0.20, P=<0.001). After commencing consumption, yogurt consumers experienced an additional increase of 0.28 cells/µL/day (95% CI; 0.10-0.46, P=0.003). When adjusting for length of time using antiretroviral medication, the additional increase explained by yogurt consumption remained 0.17 cells/µL/day (95% CI; 0.01-0.34, P=0.04). Treatment with antiretroviral medication was associated with an increase of 0.27 cells/µL/day (95% CI; 0.17-0.38, P=<0.001). CONCLUSION: The introduction of probiotic yogurt, made by local women in a low-income community in Tanzania, was significantly associated with an increase in CD4 count among consumers living with HIV.

Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with monoaryl P4 motifs.

Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa inhibitors, incorporating neutral and basic monoaryl P4 groups, ultimately producing potent inhibitors with effective levels of anticoagulant activity and extended oral pharmacokinetic profiles. However, time dependant inhibition of Cytochrome P450 3A4 was a particular issue with this series.

Highly active iridium(I) complexes for catalytic hydrogen isotope exchange.

Practically convenient methods have been developed for the preparation of new iridium complexes, possessing bulky N-heterocyclic carbene and phosphine ligands; these routinely handled complexes are highly active catalysts within directed hydrogen isotope exchange processes.

Probiotic yogurt consumption may improve gastrointestinal symptoms, productivity, and nutritional intake of people living with human immunodeficiency virus in Mwanza, Tanzania.

The gut-associated lymphoid tissue is a major site of human immunodeficiency virus (HIV) activity and significantly influences disease prognosis. Reducing immune activation due to gastroenteritis may thus help slow disease progression. Probiotic microorganisms have considerable immunomodulatory effects at the level of the gut-associated lymphoid tissue. A probiotic yogurt initiative was thus established in Mwanza, Tanzania, to improve gastrointestinal (GI) integrity and reduce the incidence and severity of opportunistic infections among people with HIV. The research objective was to retrospectively evaluate the effects of yogurt supplemented with Lactobacillus rhamnosus as an adjunct to the diet of people living with HIV on systemic and GI symptoms, daily routine activities, and nutritional intake. Eighty-five people with HIV consuming probiotic yogurt and 86 controls were interviewed. Demographics and HIV disease stage were comparable between groups. Probiotic yogurt consumers reported an ability to work a median of 2 hours more daily (P = .01), experienced a lower fever incidence (P = .01), and were more likely to achieve daily nutrient requirements for vitamin A, several B complex vitamins, and calcium (P = .02). Antiretroviral users experienced less drug-induced stomach pain (P = .02) and a lower overall impact of GI symptoms on routine activities (P = .03). The results of this study need be further substantiated because of limits imposed by the observational, retrospective study design; however, results suggest that yogurt supplemented with L rhamnosus may effectively alleviate GI symptoms and improve productivity, nutritional intake, and tolerance to antiretroviral treatment among people with HIV in Mwanza.

Highly active iridium(I) complexes for the selective hydrogenation of carbon-carbon multiple bonds.

New iridium(I) complexes, bearing a bulky NHC/phosphine ligand combination, have been established as extremely efficient hydrogenation catalysts that can be used at low catalyst loadings, and are compatible with functional groups which are often sensitive to more routinely employed hydrogenation methods.

New odourless protocols for efficient Pauson-Khand annulations.

An inexpensive and commercially available odourless additive, dodecyl methyl sulfide, has been shown to be a highly effective promoter in the Pauson-Khand cyclisation of both intra- and intermolecular substrates, affording good to excellent yields of cyclopentenone products.