[Carboxyl- C]Labelling of Four High-Affinity cPLA2α Inhibitors and Their Evaluation as Radioligands in Mice by Positron Emission Tomography.

Cytosolic phospholipase A2α (cPLA2α) may play a critical role in neuropsychiatric and neurodegenerative disorders associated with oxidative stress and neuroinflammation. An effective PET radioligand for imaging cPLA2α in living brain might prove useful for biomedical research, especially on neuroinflammation. We selected four high-affinity (IC 2.

Trivalent Gd-DOTA reagents for modification of proteins.

The development of novel protein-targeted MRI contrast agents crucially depends on the ability to derivatise suitable targeting moieties with a high payload of relaxation enhancer (, gadolinium(iii) complexes such as Gd-DOTA), without losing affinity for the target proteins. Here, we report robust synthetic procedures for the preparation of trivalent Gd-DOTA reagents with various chemical handles for site-specific modification of biomolecules. The reagents were shown to successfully label proteins through isothiocyanate ligation or through site-specific thiol-maleimide ligation and strain-promoted azide-alkyne cycloaddition.

Comparison of peripheral forearm DXA and clinical risk factor screening using FRAX® to assess the risk of HIV-associated low bone mass: a cross-sectional study.

Unlabelled: There is growing awareness that HIV infection is associated with low bone mass and fracture. DXA is a relatively scarce resource. Therefore, we evaluated two tools: peripheral DXA (pDXA) at the forearm and Fracture Risk Assessment Tool (FRAX®) to see which performed best at identifying men who should undergo DXA.

Prevalence of and risk factors for osteoporosis and fracture among a male HIV-infected population in the UK.

Rates of osteoporosis and fracture may be increased in HIV but there are few UK data. Our aim was to examine the prevalence of and risk factors for osteoporosis and fractures among a homogeneous cohort of well-characterized HIV-infected men. In total, 168 men were recruited, median age 45 years, 37 combination antiretroviral therapy (cART) naïve, 46 with <3 years cART exposure and 85 cART-exposed longer term (median >10 years).

Effects of hydroxychloroquine on immune activation and disease progression among HIV-infected patients not receiving antiretroviral therapy: a randomized controlled trial.

Context: Therapies to decrease immune activation might be of benefit in slowing HIV disease progression.

Objective: To determine whether hydroxychloroquine decreases immune activation and slows CD4 cell decline.

Design, Setting, And Patients: Randomized, double-blind, placebo-controlled trial performed at 10 HIV outpatient clinics in the United Kingdom between June 2008 and February 2011.

Angiotensin converting enzyme (ACE) and ACE2 bind integrins and ACE2 regulates integrin signalling.

The angiotensin converting enzymes (ACEs) are the key catalytic components of the renin-angiotensin system, mediating precise regulation of blood pressure by counterbalancing the effects of each other. Inhibition of ACE has been shown to improve pathology in cardiovascular disease, whilst ACE2 is cardioprotective in the failing heart. However, the mechanisms by which ACE2 mediates its cardioprotective functions have yet to be fully elucidated.

Trimetrexate and folinic acid: a valuable salvage option for Pneumocystis jirovecii pneumonia.

The best management strategy for HIV patients who fail to respond to first-line therapy for Pneumocystis jirovecii pneumonia is currently unclear. We identified all patients who were treated with trimetrexate and folinic acid who failed 7 or more days of cotrimoxazole, clindamycin-primaquine or dapsone-trimethoprim between 1996 and 2006. Trimetrexate was tolerated in 100% of cases with no treatment termination secondary to adverse drug reactions.

Making sense of syphilis: beliefs, behaviours and disclosure among gay men recently diagnosed with infectious syphilis and the implications for prevention.

Background: The resurgence of syphilis in men who have sex with men (MSM) has proved remarkably resilient in the face of innovative control and prevention interventions. Understanding the determinants of the current outbreaks has been restricted by the available data. Qualitative work is needed to understand individual and community experiences of syphilis and to help guide new prevention and control efforts.

The re-emergence of syphilis in the United Kingdom: the new epidemic phases.

Objective: The objective of this study was to characterize the resurgence of infectious syphilis in the United Kingdom between 1997 and 2003.

Study: The authors conducted a retrospective analysis of routine surveillance data from genitourinary medicine clinics and data collected through enhanced surveillance.

Results: Between 1997 and 2002, diagnoses of primary, secondary, and early latent syphilis made at genitourinary medicine clinics increased by 213% in heterosexual males, 1412% in men who have sex with men (MSM), and 22% in females.