Exercise for rotator cuff tendinopathy: Proposed mechanisms of recovery.

Rotator cuff (RC) tendinopathy is a common recurrent cause of shoulder pain, and resistance exercise is the first-line recommended intervention. Proposed causal mechanisms of resistance exercise for patients with RC tendinopathy consist of four domains: tendon structure, neuromuscular factors, pain and sensorimotor processing, and psychosocial factors. Tendon structure plays a role in RC tendinopathy, with decreased stiffness, increased thickness, and collagen disorganization.

Isolated human hepatocytes in culture display markedly different gene expression patterns depending on attachment status.

In vitro human hepatocyte cultures are a key tool in the investigation of xenobiotic toxicity and metabolism. In most in vitro hepatocyte studies, the cells are allowed to adhere to an extracellular matrix, such as collagen. Unfortunately, the ability of freshly isolated hepatocytes to adhere to collagen varies from donor to donor.

Antisense protein tyrosine phosphatase 1B reverses activation of p38 mitogen-activated protein kinase in liver of ob/ob mice.

Phosphorylation of stress-activated kinase p38, a MAPK family member, was increased in liver of ob/ob diabetic mice relative to lean littermates. Treatment of ob/ob mice with protein tyrosine phosphatase 1B (PTP1B) antisense oligonucleotides (ASO) reduced phosphorylation of p38 in liver-to below lean littermate levels-and normalized plasma glucose while reducing plasma insulin. Phosphorylation of ERK, but not JNK, was also decreased in ASO-treated mice.

Identifying toxic mechanisms using DNA microarrays: evidence that an experimental inhibitor of cell adhesion molecule expression signals through the aryl hydrocarbon nuclear receptor.

Microarray analysis of gene expression has become a powerful approach for exploring the biological effects of drugs and other chemicals. In toxicology research, gene expression profiling may help identify hazards by comparing results for an experimental compound with a database, and establish mechanistic hypotheses through examination of discrete gene changes. Here we examine the hepatic effects of a thienopyridine inhibitor of NF-kappa B-mediated expression of cellular adhesion proteins.

Reduction of protein tyrosine phosphatase 1B increases insulin-dependent signaling in ob/ob mice.

Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin receptor (IR) signal transduction and a drug target for treatment of type 2 diabetes. Using PTP1B antisense oligonucleotides (ASOs), effects of decreased PTP1B levels on insulin signaling in diabetic ob/ob mice were examined. Insulin stimulation, prior to sacrifice, resulted in no significant activation of insulin signaling pathways in livers from ob/ob mice.