F. Clinical Renal Pharmacology and Therapeutics

Literature Survey

F. Clinical Renal Pharmacology and Therapeutics     

Eosinophil cell: pray tell us what you do!

PURPOSE OF REVIEW: We will review the role of the eosinophil as an innate immune cell. There have been recent advances in the regulatory mechanisms of the eosinophil, in terms of priming and migration. Additionally, we will discuss certain pulmonary diseases that are associated with eosinophilia. RECENT FINDINGS: Rapid binding of immunoglobulin A-coated beads can prime the eosinophil cell in the trafficking process. Tissue factor has been shown to be expressed within eosinophil granules. It is believed to serve as a critical eosinophil mediator within the peripheral bloodstream. Interleukin-8 serves as a chemoattractant through IL8RA and IL8RB receptors, but patients with an IL8RA-B ht2 have peripheral eosinophilia. Interleukin-10 and eotaxin correlate with eosinophilia and an active infection prior to therapy. After therapy, interleukin-5 and 6 correlated appropriately with eosinophilia. A wide differential diagnosis exists for peripheral eosinophilia. One study has shown that 86 out of 103 patients with unknown causes for peripheral eosinophilia had positive toxocara enzyme-linked immunosorbent assay results. SUMMARY: The effect of the cytotoxic eosinophil cell is not only harmful to foreign invaders within the body, but through an intricate immunological pathway, eosinophils can become detrimental to the host organs.     

An agarose spot chemotaxis assay for chemokine receptor antagonists

Introduction

Chemokines are important players in directing the migration of cancer cells as part of the metastatic process. The aim of this study is to develop an easy-to-perform, reliable, and inexpensive assay for rapid analysis of anti-chemotactic activity of chemokine antagonists under a number of experimental conditions.

Methods

An agarose spot containing the chemokine chemoattractant is applied to a glass petri dish. Live cells in a media, both with and without a chemokine antagonist, are added to the dish and, following cell adhesion, the migration under the agarose spot is observed and analysed by microscopy.

Results

In the absence of CXCL12 in the agarose, no migration under the agarose spot is detected. In the presence of CXCL12, significant migration under the agarose spot is observed which can be retarded if a neutralising monoclonal antibody or a small molecule antagonist is added to the media.

Discussion

This experimental configuration is a reliable, inexpensive and easy-to-perform chemotaxis assay, which enables assessment of the activity of CXCR4 antagonists.     

HIV among drug users at Beth Israel Medical Center, New York City, the first 25 years

New York City experienced the first and largest HIV epidemic among injecting drug users (IDUs). Using data collected from IDUs entering the Beth Israel drug detoxification program, we trace the history of this epidemic from the mid-1970s through the early 2000s. The epidemic can best be described in terms of successive stages: (1) introduction and rapid transmission of HIV in the IDU population; (2) stabilization of HIV prevalence at a high level (over 50%); (3) a decline in incidence and prevalence, following large-scale implementation of syringe exchange programs; and (4) a sexual transmission phase, in which HIV prevalence is approximately equal among injecting and noninjecting heroin and cocaine users, and sexual transmission is more important than injecting-related transmission among IDUs. Given the current spread of HIV among IDUs in many places in the world, New York City provides a very strong example for implementation of large-scale comprehensive syringe exchange programs as early as possible in HIV epidemics among IDUs.