Local administration of L-Arginine accelerates wound closure

The process of wound healing involves tightly integrated events including inflammation, granulation tissue formation and remodeling. Systemic administration of L-arginine promotes wound healing but its global side effects are undesirable. To confine the action of L-arginine at the site of injury, we tested the effects of local administration of L-arginine on the healing of excisional wound in the rat. Full thickness excisional wounds were generated on the dorsum of adult male rats. The test wounds received 200 micro m or 400 micro m of L-arginine on day 3 and 5 post-wounding. Normal saline was injected into the sham wounds which were otherwise treated as the test wounds. Control wounds remained unmanipulated. The wound size was monitored daily by imaging. To determine the rate of wound closure, wound images were scanned and the rate of size reduction was analyzed and quantified by ScnImage software. The repaired tissues were harvested on day 12 post-wounding. The tissue sections were prepared and stained for microscopic examination. Wounds treated with L-arginine showed a significant increase in the rate of wound closure. The morphology of basal keratinocytes was altered, and the thickness of neoepidermis was markedly reduced in the wounds treated with L-arginine. Both tested dose of L-arginine were equally effective. Local administration of L-arginine accelerates wound closure and has profound effects on keratinocytes performance during the process of healing. Therefore, it can be potentially used for treatment of skin disorders, in particular, those characterized by hyperkeratosis

Jak-stat signaling pathway of interferons system: snapshots

Interferons [IFNs] are a family of small regulatory glycoproteins that play a central role in the defense against viral infections. Although IFNs have been initially discovered as antiviral factors, today they are known as an integral part of the cytokine network that affect a wide range of biological processes. IFNs exert their pleiotropic effects through their multisubunit cell surface receptors in a species specific manner that is believed to be controlled at the receptor and the post-receptor levels. Although IFN-mediated signaling and transcription activation of cellular gene expression is currently best understood in the context of the JAK-STAT signal transduc-tion, additional IFNs signaling pathways may also act in certain conditions. The Janus family of tyrosine kinase [JAK] enzymes and two families of transcriptional regulators, signal transducer and activator of transcription [STATS] and IFN regulatory factors [IRFs], are the principal components of the JAK-STAT pathway. Overlapping subsets of JAKS are involved in signaling by type I [IFN-alpha/B] and type II [IFN-y IFNs, indicating that the receptor subunits confer specificity for activating particular JAK family members. A considerable cross talk can exist between separate signaling pathways. The emergence of new tools and approaches for study of IFNs signaling has been an exercise in coming to respect the level of complexity of IFNs system. For many years, IFNs have been satisfactorily used in many clinical trials. However, their serious side effects remain as the major concern in clinical use of IFNs. A better understanding of the exact mechanism involved in IFNs signaling pathways and the structure-function relationships of the IFNs system components will allow researchers to improve and expand the therapeutic potential of these naturally occurring molecules. IFNs actions are mediated through multiple signaling pathways. However, due to the space limitation, this review will focus primarily on the IFNs-mediated JAK-STAT pathway