Why is the rectal route for NSAIDS favorable for preventing post-ERCP pancreatitis?

Objective: Acute pancreatitis is a frequent, burdensome adverse event of endoscopic retrograde cholangiography (ERCP). Rectal nonsteroidal anti-inflammatory drugs (NSAIDs) have reduced post-ERCP pancreatitis (PEP) risk by about 50 % and show greater efficacy over parenteral or oral administration, although the mechanism for its superiority remains unclear. To probe this question, we investigated in a preclinical model, the pharmacokinetics in the blood, pancreas and other tissues of the NSAID diclofenac given via the rectal, intravenous, or intragastric routes.

Rectal administration of tacrolimus protects against post-ERCP pancreatitis in mice.

Objective: There is an unmet clinical need for effective, targeted interventions to prevent post-ERCP pancreatitis (PEP). We previously demonstrated that the serine-threonine phosphatase, calcineurin (Cn) is a critical mediator of PEP and that the FDA-approved calcineurin inhibitors, tacrolimus (Tac) or cyclosporine A, prevented PEP. Our recent observations in preclinical PEP models demonstrating that Cn deletion in both pancreatic and hematopoietic compartments is required for maximal pancreas protection, highlighted the need to target both systemic and pancreas-specific Cn signaling.

Preclinical safety evaluation of calcineurin inhibitors delivered through an intraductal route to prevent post-ERCP pancreatitis demonstrates endocrine and systemic safety.

Objective: There is an urgent need for safe and targeted interventions to mitigate post-ERCP pancreatitis (PEP). Calcineurin inhibitors (CnIs) offer therapeutic promise as calcineurin signaling within acinar cells is a key initiating event in PEP. In previous proof-of-concept studies using experimental models, we showed that concurrent intra-pancreatic ductal administration of the CnIs, tacrolimus (Tac) or cyclosporine A (CsA) with the ERCP radiocontrast agent (RC) prevented PEP.

Development of a fluorescence resonance energy transfer-based intracellular assay to identify novel enterovirus 71 antivirals.

Enterovirus 71 (EV71) is considered one of the most virulent pathogens in the family Picornaviridae. However, there have been no effective treatments for the severe complications caused by EV71. Development of new drugs against targets that are essential for viral replication often requires screening large collections of compounds, for which a high-throughput screening platform is needed.

Which kindergarten children are at greatest risk for attention-deficit/hyperactivity and conduct disorder symptomatology as adolescents?

We sought to identify which kindergarten children are simultaneously at risk of moderate or severe symptomatology in both attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) as adolescents. These risk factor estimates have not been previously available. We conducted multinomial logistic regression analyses of multiinformant ratings by the end of middle school of a population-based, longitudinal sample of children followed from kindergarten to eighth grade (N = 7,456).

Reading, Mathematics, and Behavioral Difficulties Interrelate: Evidence from a Cross-lagged Panel Design and Population-based Sample.

We examined three questions. First, do reading difficulties increase children's risk of behavior difficulties? Second, do behavioral difficulties increase children's risk of reading difficulties? Third, do mathematics difficulties increase children's risk of reading or behavioral difficulties? We investigated these questions using a sample of 9,324 children followed from third to fifth grade as they participated in a nationally representative dataset, conducting multilevel logistic regression modeling and including statistical control for many potential confounds. Results indicated that poor readers in third grade were significantly more likely to display poor task management, poor self-control, poor interpersonal skills, internalizing behavior problems, and externalizing behavior problems in fifth grade (odds ratio [OR] range = 1.

Mesangial cells of lupus-prone mice are sensitive to chemokine production.

Infectious antigens may be triggers for the exacerbation of systemic lupus erythematosus. The underlying mechanism causing acceleration and exacerbation of lupus nephritis (LN) is largely unknown. Bacterial lipopolysaccharide (LPS) is capable of inducing an accelerated model of LN in NZB/W mice, featuring diffuse proliferation of glomerular resident cells.