Allopurinol Protective Effect of Renal Ischemia by Downregulating TNF-α, IL-1ß, and IL-6 Response.

Allopurinol is a well-known antioxidant that protects tissue against ischemia and reperfusion injury, blocking purine catabolism, and possibly reducing TNF-α and other cytokines. It also plays a significant role in reducing the inflammatory processes by inhibiting chemotaxis and other inflammatory mediators. The objective of this study was to define the role of allopurinol regarding kidney ischemic injury particularly as to its effect on inflammatory molecules such as TNF-α, IL-1ß, and IL-6 response. One hundred and twenty five rats were subjected to warm renal ischemia. Five more animals were included as sham. Animal survival and plasma levels of lipid peroxidation, myeloperoxidase, lactate dehydrogenase, glutathione, urea, creatinine, and cytokines were determined. Inflammatory parameters (TNF-α, IL-1ß, and IL-6) were measured in all groups by quantitative immunosorbent assay. Further, immunohistological and histopathological studies were carried out on animals treated prior to, or following reperfusion with 10 and 50 mg/kg of Allopurinol. The statistical analysis included ANOVA and Fisher test as well as χ2 test. Significance was reached at a p < 0.05. The results of this study indicated that Allopurinol protected against kidney ischemia-reperfusion injury since significantly better results of survival, biochemical analysis, and histopathological testing were observed in treated animals as compared to ischemic controls. In conclusion, Allopurinol protected ischemic kidneys through a mechanism associated with downregulation of TNF-α, IL-1 ß, and IL-6, in addition to other well-known effects such as decreased lipid peroxidation and neutrophil activity. It also increased antioxidant capacity and diminished endogenous peroxidase stain in renal ischemic tissue. Therefore, this experiment showed an effectiveness of allopurinol protection against proteomic and morphological damage.

Pharmacology of Ischemia-Reperfusion. Translational Research Considerations.

Ischemia-reperfusion (IRI) is a complex physiopathological mechanism involving a large number of metabolic processes that can eventually lead to cell apoptosis and ultimately tissue necrosis. Treatment approaches intended to reduce or palliate the effects of IRI are varied, and are aimed basically at: inhibiting cell apoptosis and the complement system in the inflammatory process deriving from IRI, modulating calcium levels, maintaining mitochondrial membrane integrity, reducing the oxidative effects of IRI and levels of inflammatory cytokines, or minimizing the action of macrophages, neutrophils, and other cell types. This study involved an extensive, up-to-date review of the bibliography on the currently most widely used active products in the treatment and prevention of IRI, and their mechanisms of action, in an aim to obtain an overview of current and potential future treatments for this pathological process. The importance of IRI is clearly reflected by the large number of studies published year after year, and by the variety of pathophysiological processes involved in this major vascular problem. A quick study of the evolution of IRI-related publications in PubMed shows that in a single month in 2014, 263 articles were published, compared to 806 articles in the entire 1990.

Randomized clinical trial of a new cyanoacrylate flexible tissue adhesive (Adhflex) for repairing surgical wounds.

UNLABELLED: The use of synthetic adhesives such as cyanoacrylates for closing surgical wounds remains controversial. In a multicenter, prospective and randomized clinical trial, we compared a new cyanoacrylate elastic tissue adhesive, Adhflex, with standard suturing methods for repairing surgical wounds. Sixty patients who underwent surgery for inguinal hernia were randomly chosen for Adhflex or standard silk suture. We evaluated wound closure time and parameters related to wound healing and complications using the Hollander Scale; overall surgeon, patient, and independent evaluator satisfaction with scar appearance using a visual analog scale; and scar cosmesis and cosmetic outcome using the Patient and Observer Scar Assessment Scale. The major finding of this study was that surgical wound closure time (minutes) was significantly lower (p < 0.05) when using Adhflex (1.50 ± 0.63) than when using sutures (2.23 ± 0.66), reducing surgery costs. Patient, surgeon and independent evaluator satisfaction was greater with Adhflex (p < 0.05). No differences were found in the final cosmetic outcome of surgical wounds (p > 0.05). The results of this clinical trial showed that Adhflex could be considered a promising and suitable wound closure method. Undoubtedly, lower operating room times will reduce overall surgical costs. Cosmetic outcomes in the medium term are comparable to those seen with sutures, yet there is no need for dressing changes, postoperative wound checks, or removal of stitches or clips. The comfort of the patient is an important factor when considering wound closure methods. REGISTRATION NUMBER: Eudra CT2012-002701-22.