International journal of molecular medicine
-
Review
Mechanism of cardioprotection by resveratrol, a phenolic antioxidant present in red wine (Review).
Coronary heart disease (CHD) has been and remains a major contributor to morbidity and mortality in developed countries. The most common form of CHD in the western world is atherosclerosis (AS), especially of the major coronary arteries. Failure to maintain an intact endothelium, as a result of episodic and/or persistent injury and perturbation of the vascular endothelium, promotes formation of fatty streaks which are considered initiation events of AS. ⋯ A review of biosynthesis of resveratrol and its presence in food groups and wines will follow. Recent studies relating exposure to wine/resveratrol with reduction in myocardial damage during ischemia-reperfusion, modulation of vascular cell functions, inhibition of LDL oxidation, and suppression of platelet aggregation will be presented. The last section of this review will focus on a discussion of mechanism(s) by which resveratrol acts as a potential cardioprotective agent.
-
Focal cerebral ischemia activates the nuclear protein poly(ADP-ribose) polymerase (PARP) by single DNA strand breaks which leads to energy depletion and cell necrosis. Deletion or inhibition of PARP protects against ischemic brain injury. Here we examined the neuroprotective effect of PJ34, a novel potent inhibitor of PARP in vitro and in vivo. ⋯ PJ34 significantly protected in a 4 h, but not in a 24 h permanent occlusion model. In conclusion, PJ34, a novel, potent inhibitor of PARP exerts massive neuroprotective agents, with a significant therapeutic window of opportunity. The present work strengthens the concept that pharmacological PARP inhibition may be a suitable approach for the treatment of acute stroke in man.
-
Inflammatory bowel diseases are considered to be related to dysregulation of pro- and anti-inflammatory cytokines in the intestinal wall. We investigated the levels of TNFalpha, IFNgamma, and IL-10 mRNA expression in intestinal tissues resected from the patients with Crohn disease (CD) (n=29), ulcerative colitis (UC) (n=8), and controls (n=8) using reverse transcription-polymerase chain reaction (RT-PCR). In addition, we examined the relationship between the expression of these cytokine mRNA and their clinical conditions using CD activity index (CDAI) and Nutritional Surgical Risk Index (NSRI). ⋯ While the remaining tissues (n=6) showed low levels of IL-10 expression despite high levels of TNFalpha expression in inflamed CD tissues, and 4 of these 6 patients had high CDAI and low NSRI. Furthermore, in low nutritional CD patients (NSRI <40, n=13), the levels of IL-10 mRNA to inhibit pro-inflammatory cytokines were poorer than in good nutritional patients (NSRI >/=40, n=16). These findings suggest the overexpressions of TNFalpha and IFNgamma in CD, and less producibility of IL-10 against these cytokine might lead to development of severe CD.
-
Review
Organ dysfunction following hemorrhage and sepsis: mechanisms and therapeutic approaches (Review).
Despite significant advances in the management of trauma victims, sepsis and the ensuing multiple organ failure remain the leading causes of death in the surgical intensive care unit. Although much effort has been focused on the mediators released in large quantities following shock and sepsis, blockade of mediators such as proinflammatory cytokines has not yet resulted in a successful therapy. However, as more studies are forthcoming, the mechanisms responsible for cell and organ dysfunctions following trauma-hemorrhage and sepsis are becoming better understood, and promising new therapeutic approaches are currently being evaluated. ⋯ In this review we focus first on factors and mediators responsible for producing cell and organ dysfunctions, especially hepatocellular dysfunction, following trauma, hemorrhagic shock, and sepsis. The changes in signaling transduction pathways will also be discussed, specifically the role of mitogen-activated protein kinases, transcription factors, nitric oxide, heat shock proteins, and inflammatory cytokines in the development of cell and organ dysfunctions following trauma-hemorrhage and sepsis. Moreover, potential therapeutic approaches for improving cell and organ functions under adverse circulatory conditions are included.
-
IL-4 and IL-13 are unique cytokines, in that they induce IgE synthesis in B cells and TH2 type differentiation in T cells. Both cytokines exert their biological activities by binding to their functional receptors on target cells. These receptors are thought to be composed as heterodimers, both having the IL-4R alpha chain (IL-4Ralpha) as a component. ⋯ One polymorphism existing in the IL-4Ralpha gene, Ile50Val, is verified to correlate with atopy by both genetic and functional aspects. On the contrary, the correlation between another polymorphism on the IL-4Ralpha gene, Arg551Gln, and atopy is still controversial. The strategy used in these studies should lead to identification of other genes involved in atopy.