Cachexia is a life-threatening wasting syndrome lacking effective treatment, which arises in many cancer patients. Although ostensibly induced by multiple tumor-produced cytokines (tumorkines), their functional contribution to initiation and progression of this syndrome has proven difficult to determine. In this study, we used adeno-associated viral vectors to elevate circulating levels of the ...

BACKGROUND: No systematic comparison has been conducted in Fiji using all suitable surveys of type 2 diabetes mellitus (T2DM) and obesity prevalence after standardizing methodology and definitions. METHODS: Unit records from six surveys of Fiji adults were variously adjusted for age, ethnicity (Fiji Melanesians, i-Taukei, and Fijians of Asian Indian descent [Indians]) and urban-rural by ...

Oxidative stress and inflammation are inextricably linked and play essential roles in the initiation and progression of diabetes complications such as diabetes-associated atherosclerosis and nephropathy. Bolstering antioxidant defenses is an important mechanism to lessen oxidative stress and inflammation. In this study, we have used a novel analog of the NFE2-related factor 2 (Nrf2) agonist bar...

We have recently identified conventional B2 cells as atherogenic and B1a cells as atheroprotective in hypercholesterolemic ApoE(-/-) mice. Here, we examined the development of atherosclerosis in BAFF-R deficient ApoE(-/-) mice because B2 cells but not B1a cells are selectively depleted in BAFF-R deficient mice. We fed BAFF-R(-/-) ApoE(-/-) (BaffR.ApoE DKO) and BAFF-R(+/+)ApoE(-/-) (ApoE KO) mic...

Catecholamines regulate the β-adrenoceptor/cyclic AMP-regulated protein kinase A (cAMP/PKA) pathway. Deregulation of this pathway can cause apoptotic cell death and is implicated in a range of human diseases, such as neuronal loss during aging, cardiomyopathy and septic shock. The molecular mechanism of this process is, however, only poorly understood. Here we demonstrate that the β-adrenocepto...

A concise synthesis of both E-isomers of 2S-amino-3-(20-aminomethyl-cyclopropyl)propionic acid, new methano-Llysines, is described. The synthetic route includes nine steps from L-methionine, with a key step involving the cyclopropanation of an intermediate E-allylic alcohol. The resultant hydroxymethylcyclopropanes were readily separated and converted into the title a-amino acids. The stereo...

BACKGROUND: Currently, the relationship between circulating lipids and abdominal aortic aneurysm (AAA) is unclear. We conducted a lipidomic analysis to identify serum lipids associated with AAA presence. Secondary analyses assessed the ability of models incorporating lipidomic features to improve stratification of patient groups with and without AAA beyond traditional risk factors. METHODS AN...

A process to identify and target a selected population at risk of heart failure (HF) could facilitate screening and prevention. We sought to develop an effective screening process from clinical characteristics, functional capacity, and electrocardiogram (ECG). Asymptomatic subjects ≥65 years, with ≥1 HF risks were recruited from the community. Subjects with valvular disease, ejection fraction <...

AIM: To examine the relationships of serum markers of inflammation and endothelial function to diabetic retinopathy. METHODS: We recruited 224 patients with diabetes (85 with Type 1 and 139 with Type 2 diabetes) aged 18-70 years. Serum markers of inflammation (high-sensitivity C-reactive protein) and endothelial function (soluble intercell adhesion molecule-1, vascular cell adhesion molecule...

Albuminuria and a reduced glomerular filtration rate are conventional predictors of a future decline in kidney function in patients with type 2 diabetes mellitus. Using a nested case-control study we assessed whether circulating transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7) levels more accurately predict renal end points than the conventional markers. Cases wer...

It is known that low testosterone (T) and high cortisol levels are associated with hypertension as well as with chronic stress, linking stress with elevated blood pressure (BP). However, the association between acute stress-, chronic stress responses and BP is not clear in Africans. Therefore, we examined the association between cortisol, psychological distress and BP responses in low- and high...

BACKGROUND AND PURPOSE: The β1 -adrenoceptor has at least two binding sites, high and low affinity sites (β1H and β1L , respectively), which mediate cardiostimulation. While β1H - adrenoceptor can be blocked by all clinically used β-blockers, β1L -adrenoceptor is relatively resistant to blockade. Thus, chronic β1L -adrenoceptor activation may mediate persistent cardiostimulation, despite the c...

Platelets have a key role in atherogenesis and its complications. Both hypercholesterolemia and increased platelet production promote atherothrombosis; however, a potential link between altered cholesterol homeostasis and platelet production has not been explored. Here we show that transplantation of bone marrow deficient in ABCG4, a transporter of unknown function, into Ldlr(-/-) mice resulted...

OBJECTIVES: To examine the association between prior chlamydia and gonorrhoea infections and adverse obstetric outcomes. METHODS: Records of women resident in New South Wales, Australia with a singleton first birth during 1999-2008 were linked to chlamydia and gonorrhoea notifications using probabilistic linkage. Obstetric outcomes and potential confounders were ascertained from the birth reco...

BACKGROUND: Atrial fibrillation (AF) and left ventricular systolic dysfunction (LVSD) frequently co-exist despite adequate rate control. Existing randomized studies of AF and LVSD of varying etiologies have reported modest benefits with a rhythm control strategy. OBJECTIVES: The goal of this study was to determine whether catheter ablation (CA) for AF could improve LVSD compared with med...

NEW FINDINGS: What is the central question of this study? What is the potential role of endothelial NO production via overexpression of the l-arginine transporter, CAT1, as a mitigator of cardiac hypertrophy? What is the main finding and its importance? Augmentation of endothelium-specific l-arginine transport via CAT1 can attenuate pressure-overload-dependent cardiac hypertrophy and fibrosi...

OBJECTIVE: Low birth weight (LBW) and preterm birth have been associated with adverse adult outcomes, including hypertension, insulin resistance, cardiovascular disease, and reduced bone mass. It is unknown whether LBW and preterm birth affect the risk of osteoarthritis (OA). This study aims to examine whether LBW and preterm birth were associated with the incidence of knee and hip arthroplast...

The accumulation of lipid at ectopic sites, including the skeletal muscle and liver, is a common consequence of obesity and is associated with tissue-specific and whole body insulin resistance. Exercise is well known to improve insulin resistance by mechanisms not completely understood. We performed lipidomic profiling via mass spectrometry in liver and skeletal muscle samples from exercise-tra...

AIMS/HYPOTHESIS: We determined whether: (1) an acute lipid infusion impairs skeletal muscle AMP-activated protein kinase (AMPK)α2 activity, increases inducible nitric oxide synthase (iNOS) and causes peripheral insulin resistance in conscious, unstressed, lean mice; and (2) restoration of AMPKα2 activity during the lipid infusion attenuates the increase in iNOS and reverses the defect in insuli...

BACKGROUND: Catheter-based renal sympathetic denervation (RDN) reduces office blood pressure (BP) in patients with resistant hypertension according to office BP. Less is known about the effect of RDN on 24-hour BP measured by ambulatory BP monitoring and correlates of response in individuals with true or pseudoresistant hypertension. METHODS AND RESULTS: A total of 346 uncontrolled hypertens...