Low-dose hydralazine reduces albuminuria and glomerulosclerosis in a mouse model of obesity-related chronic kidney disease.

Aim: To determine, using a mouse model of obesity, whether low-dose hydralazine prevents obesity-related chronic kidney disease (CKD).

Methods: From 8 weeks of age, male C57BL/6 mice received a high-fat diet (HFD) or chow, with or without low-dose hydralazine (25 mg/L) in drinking water, for 24 weeks. Biometric and metabolic variables, renal function and structural changes, renal global DNA methylation, DNA methylation profile and markers of renal fibrosis, injury, inflammation and oxidative stress were assessed.

Blood DNA Methylation Predicts Diabetic Kidney Disease Progression in High Fat Diet-Fed Mice.

Diabetic kidney disease (DKD) progresses at different rates among patients with type 2 diabetes mellitus (T2D). Early identification of patients with a higher risk of DKD progression is essential to improve prognosis. Epigenetic modifications, particularly DNA methylation, have been independently implicated in T2D and chronic kidney disease.

Novel Role of Gestational Hydralazine in Limiting Maternal and Dietary Obesity-Related Chronic Kidney Disease.

Background: Maternal obesity is a risk factor for chronic kidney disease (CKD) in offspring, underpinning the theory of the developmental origins of health and disease. DNA methylation has been implicated in the programming of adult chronic disease by maternal obesity, therefore, DNA demethylating agents may mitigate offspring risk of disease. In rodent models, low-dose hydralazine has previously been shown to reduce renal fibrosis via DNA demethylation.

Lysyl oxidase inhibitors attenuate cyclosporin A-induced nephropathy in mouse.

Calcineurin inhibitors, such as Cyclosporin (CsA), are the mainstay of anti-rejection therapy in solid organ transplants but can paradoxically induce progressive nephropathy characterised by renal dysfunction and interstitial fibrosis. Lysyl oxidases (LOXs), a group of enzymes that catalyse extracellular matrix (ECM) crosslinking, were shown to implicate in tissue scarring. It is hypothesized that inhibition of these enzymes may render therapeutic effects against CsA-induced nephropathy.

Low-dose hydralazine during gestation reduces renal fibrosis in rodent offspring exposed to maternal high fat diet.

Background: Maternal high fat diet (HFD) promotes chronic kidney disease (CKD) in offspring. This is in accordance with the theory of fetal programming, which suggests adverse conditions occurring in utero predispose offspring to chronic conditions later in life. DNA methylation has been proposed as a key mechanism by which fetal programming occurs and is implicated in CKD progression.

Comorbidities Rather Than Age Are Associated With the Use of Immunomodulators in Elderly-onset Inflammatory Bowel Disease.

Background And Aim: The use of immunomodulators (IMs) is often avoided in elderly patients with inflammatory bowel disease (IBD) due to concerns about complications. Our aim is to compare the use of IMs in elderly and younger patients with Crohn's disease (CD) or ulcerative colitis (UC) and identify markers that predict their use.

Methods: In this retrospective cohort study, patients diagnosed with IBD from 1970 to 2009 were recruited from the "Sydney IBD Cohort.

Exercise-induced brain-derived neurotrophic factor expression: Therapeutic implications for Alzheimer's dementia.

Emerging evidence indicates that moderate intensity aerobic exercise is positively correlated with cognitive function and memory. However, the exact mechanisms underlying such improvements remain unclear. Recent research in animal models allows proposition of a pathway in which brain-derived neurotrophic factor (BDNF) is a key mediator.

Primary sclerosing cholangitis as an independent risk factor for colorectal cancer in the context of inflammatory bowel disease: a review of the literature.

To examine and evaluate recent evidence regarding the epidemiology, pathogenesis and management of colorectal cancer (CRC) development in inflammatory bowel disease (IBD)-primary sclerosing cholangitis (PSC) patients. Using the PubMed database, a literature search was conducted for relevant articles in English from the past 10 years. Relevant studies investigating PSC as a risk factor for CRC in IBD in the context of incidence and prevalence, pathogenesis, prevention and prognosis were included in this review.

Early use of thiopurines or methotrexate reduces major abdominal and perianal surgery in Crohn's disease.

Background: Earlier introduction of immunomodulators (IM) thiopurine or methotrexate is advocated to improve Crohn's disease (CD) outcomes, but whether abdominal surgery can be prevented remains controversial.

Methods: A specialist-referred cohort of CD was recruited from 1970 to 2009. Early IM use was defined as commencement of azathioprine or methotrexate within 3 years of CD diagnosis and adherence of at least 6 months.