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  • NO is synthesized from L arginine by the

    2018-10-29

    NO is synthesized from L-arginine by the NOS family of enzymes. Two NOS isoforms were previously identified: constitutive NOS and iNOS. Constitutive NOS comprises endothelial NOS (eNOS) and neuronal NOS. NO plays a crucial role in the homeostasis of hepatic circulation under physiological conditions. Furthermore, a large amount of NO is produced in response to various stress-related conditions including hepatic ischemia–reperfusion. Under a stable condition, only the physiological amount of NO produced by eNOS maintains hepatic vascular tone. Nevertheless, the large amount of NO produced by iNOS induces vasodilatation. Therefore, the induction and activation of iNOS constitute a crucial biological mechanism for coping with stress-related conditions. The heat shock response is induced by various stimuli including thermal, chemical, and physical stresses as well as short-term ischemia. Organisms typically respond to such detrimental insults by inducing a group of protective proteins called HSPs. HSPs are classified into multimember ret inhibitor on the basis of the molecular weights of protein they encode (HSP90, HSP70, HSP60, and the small HSP family). HSP70 is one of the most extensively studied mammalian HSPs. HSPs, particularly HSP70, play a major role in thermotolerance as well as in protecting against oxygen radical toxicity and ischemia-reperfusion injury. PCNA levels are directly correlated with cell proliferation and DNA synthesis rates and with the cell proliferative state. Prelich et al studied post-hepatectomy regeneration in mice and reported that regeneration with PCNA-positive cell augmentation increased after 24 hours. Tanoue et al demonstrated that a 50% reduced liver promoted hepatic remnant regeneration, which was accentuated by N-acetylcysteine, according to the total hepatocyte number and PCNA levels. In previous studies, the effects of ischemic preconditioning have been generally evaluated immediately or a few hours after the maneuver is performed. To the best of our knowledge, our study is the first to evaluate the long-term effects of ischemic preconditioning (on the 2nd day, 24 hours later) and demonstrate that both PCNA and HO-1 expressions significantly increased after the longer hepatic ischemia (45 minutes), which decreased with ischemic preconditioning. Because longer ischemic insults probably induce more reactive production of PCNA and HO-1, PCNA and HO-1 expressions may have significantly increased after 45-minute ischemia compared with that after 30-minute ischemia. Nevertheless, why ischemic preconditioning significantly reduced PCNA and HO-1 expressions in the 45-minute ischemia groups remains unknown. Whether the long-term effects of ischemic preconditioning stabilize the liver—resulting in reduced PCNA and HO-1 expressions after 45-minute ischemia—warrants further elucidation. Hypoxia-inducible factor (HIF)-1 and HIF-2 are hetreodimeric basic helix–loop–helix transcription factors from the Per–ARNT–Sim family. Their basic helix–loop–helix domains mediate dimerization and bind to contact the DNA of target genes and activate transcription. HIFs are universal cellular oxygen-sensitive transcription factors that activate several hypoxia-responsive genes, some of which are responsible for protective cellular functions. During organ donation, allografts are exposed to hypoxia and ischemia for significant periods. Exploiting this pathway during donor management and organ preservation may prevent or reduce allograft injury and improve organ transplantation outcomes. The role of HIFs warrants exploration in a future study.
    Acknowledgments This study was supported by Grant No. NSC102-2314-B-182A-073 from the National Science Council of the Republic of China.
    Introduction Appendicitis is a common pediatric surgical emergency. Despite widespread familiarity with this disease, appendicitis continues to pose a significant diagnostic challenge to clinicians. Two previous reports showed that despite advances in ultrasound and computed tomography imaging, perforation rates in children ≤6 years have ranged from 54% to 74% over the past three decades.