Heterogeneity in Pancreatitis: Recognizing Heterogeneity and Its Role in the Management of Pancreatitis. Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

Both the clinical management and study of recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) is complicated by significant heterogeneity in the etiology, mechanisms, symptoms, and complications of pancreatitis. The National Institutes of Diabetes and Digestive and Kidney Disease (NIDDK) recently convened a workshop to address current knowledge and knowledge gaps in the field. Preclinical models that better replicate human disease are important for development of new therapies.

Lack of involvement of CEP adducts in TLR activation and in angiogenesis.

Proteins that are post-translationally adducted with 2-(ω-carboxyethyl)pyrrole (CEP) have been proposed to play a pathogenic role in age-related macular degeneration, by inducing angiogenesis in a Toll Like Receptor 2 (TLR2)-dependent manner. We have investigated the involvement of CEP adducts in angiogenesis and TLR activation, to assess the therapeutic potential of inhibiting CEP adducts and TLR2 for ocular angiogenesis. As tool reagents, several CEP-adducted proteins and peptides were synthetically generated by published methodology and adduction was confirmed by NMR and LC-MS/MS analyses.

A subset of human uterine endometrial macrophages is alternatively activated.

Problem: Human uterine macrophages must maintain an environment hospitable to implantation and pregnancy and simultaneously provide protection against pathogens. Although macrophages comprise a significant portion of leukocytes within the uterine endometrium, the activation profile and functional response of these cells to endotoxin are unknown.

Method Of Study: Flow cytometric analysis of surface receptors and intracellular markers expressed by macrophages isolated from human endometria was performed.

NMDA receptors are expressed by small-cell lung cancer and are potential targets for effective treatment.

We previously showed that functional N-methyl-D-aspartate (NMDA) receptors are expressed by human neuroblastoma cells. In this study we demonstrate functional NMDAR1 and NMDAR2 receptors are expressed by small-cell lung cancer (SCLC) classical cell lines NCI H146, NCI H345, and DMS 53, by variant cell line NCI H82, and by most SCLC tumors, and that these receptors are important for the growth of human SCLC tumor xenografts in mice. Reverse transcription-polymerase chain reaction demonstrated mRNA for both receptors, with sequences identical to those for human mRNAs, are expressed in all four cell lines, and these generated proteins of the expected sizes 120 and 170 kDa.

Estradiol attenuates lipopolysaccharide-induced CXC chemokine ligand 8 production by human peripheral blood monocytes.

Regulation of the inflammatory response is imperative to the maintenance of immune homeostasis. Activated monocytes elaborate a broad variety of proinflammatory cytokines that mediate inflammation, including CXCL8. Release of this chemokine attracts neutrophils to sites of bacterial invasion and inflammation; however, high levels of CXCL8 may result in excessive neutrophil infiltration and subsequent tissue damage.