Establishing patient-specific criteria for selecting the optimal upper extremity vascular access procedure

Objective

The Kidney Disease Outcome Quality Initiative and Fistula First Breakthrough Initiative call for the indiscriminate creation of arteriovenous fistulas (AVFs) over arteriovenous grafts (AVGs) without providing patient-specific criteria for vascular access selection. Although the U.S. AVF rate has increased dramatically, several reports have found that this singular focus on increasing AVFs has resulted in increased AVF nonmaturation/early failure and a high prevalence of catheter dependence. The objective of this study was to determine the appropriateness of vascular access procedures in clinical scenarios constructed with combinations of relevant factors potentially influencing outcomes.

Blood-based tumor fibrosis markers as diagnostic and prognostic biomarkers in patients with biliary tract cancer

Biliary tract cancer (BTC) is characterized by a desmoplastic extracellular matrix (ECM). We tested the diagnostic and prognostic use of seven circulating biomarkers of ECM remodeling: pro-peptides of type III collagen (PRO-C3), VI (PRO-C6) and XI (PRO-C11), matrix metalloprotease (MMP) degraded type III collagen (C3M) and type IV collagen (C4M) fragments, granzyme B degraded type IV collagen fragments (C4G) and MMP degraded and citrullinated vimentin (VICM) a marker of macrophage activation. The study included 269 patients with all stages of BTC and 49 patients with benign biliary tract diseases. Serum samples from BTC patients were collected before surgery, or before first- or second-line chemotherapy. C3M, C4M, PRO-C3, PRO-C6, PRO-C11 and VICM levels were elevated in patients with BTC compared to patients with benign disease. Receiver operating characteristics curve analyses identified PRO-C3 (area under curve [AUC] = 0.87) as the ECM marker with the best diagnostic performance. The ECM biomarkers correlated with inflammation biomarkers (C-reactive protein [CRP], interleukin-6 [IL-6] and YKL-40) but not with CA19-9. To investigate prognostic performance, patients were split into three cohorts (first-line, second-line and surgery). Elevated ECM biomarker levels were associated with short overall survival (OS), but only pretreatment PRO-C3 and PRO-C6 were associated with OS in both the first-line and second-line settings when adjusting for CA19-9, performance status and stage in a multivariate Cox-regression analyses. Our results indicate that collagen remodeling is increased in patients with BTC and associated with survival. The collagen pro-peptides (PRO-C3 and PRO-C6) could be used as novel biomarkers in these patients.     

Conditional MHC class I ligands and peptide exchange technology for the human MHC gene products HLA-A1, -A3, -A11, and -B7

Major histocompatibility complex (MHC) class I multimer technology has become an indispensable immunological assay system to dissect antigen-specific cytotoxic CD8(+) T cell responses by flow cytometry. However, the development of high-throughput assay systems, in which T cell responses against a multitude of epitopes are analyzed, has been precluded by the fact that for each T cell epitope, a separate in vitro MHC refolding reaction is required. We have recently demonstrated that conditional ligands that disintegrate upon exposure to long-wavelength UV light can be designed for the human MHC molecule HLA-A2. To determine whether this peptide-exchange technology can be developed into a generally applicable approach for high throughput MHC based applications we set out to design conditional ligands for the human MHC gene products HLA-A1, -A3, -A11, and -B7. Here, we describe the development and characterization of conditional ligands for this set of human MHC molecules and apply the peptide-exchange technology to identify melanoma-associated peptides that bind to HLA-A3 with high affinity. The conditional ligand technology developed here will allow high-throughput MHC-based analysis of cytotoxic T cell immunity in the vast majority of Western European individuals.     

Listening to neuropeptides by microdialysis: Echoes and new sounds?

Neuropeptides represent the largest class of neuromessengers in the central nervous system. They are involved in the regulation of growth processes, reproduction, social behavior, emotion/motivation and cognition. Particularly in subcortical structures, neuropeptides act as neuromodulators, which reach their target sites via diffusion through the extracellular space. This route of information transfer together with the ability of neurons to release neuropeptides from their whole membrane surface predisposes neuropeptides for microdialysis experiments. This review outlines the special characteristics of neuropeptide signaling in relation to other classes of neuromessengers. It further provides a survey of the application of the microdialysis technique for monitoring neuropeptide release patterns in laboratory rodents exemplarily for the two neuropeptides arginine vasopressin and oxytocin, discusses pros and cons of such experiments and outlines perspectives for future neuroendocrine studies in rats and mice.     

Differential modulation of inflammatory pain by a selective estrogen receptor beta agonist

To understand the contribution of the estrogen receptor beta, the potent and selective agonist ERb-131 was evaluated in animal models of inflammatory pain. In paradigms of acute and persistent inflammatory pain, ERb-131 did not alleviate the nociception induced by either carrageenan or formalin. However, in the chronic complete Freund's adjuvant model, ERb-131 resolved both inflammatory and hyperalgesic components. Thus, ERb-131 is sufficient to alleviate chronic but not acute inflammatory pain states.