Structure Effect on Antioxidant Activity of Catecholamines toward Singlet Oxygen and Other Reactive Oxygen Species in vitro

The reactivity of catecholamine neurotransmitters and the related metabolites were precisely investigated toward 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and reactive oxygen species. Catecholamines reacted immediately with DPPH radicals, their reactivity being stronger than that of ascorbic acid as a reference. Superoxide scavenging activities of catecholamines determined by WST-1 and electron spin resonance (ESR) spin trapping methods were also high. Whereas tyrosine, the dopamine precursor showed no reactivity toward superoxide. The reactivity toward singlet oxygen was evaluated by observing specific photon emission from singlet oxygen. The results revealed that reactivity of catecholamines was markedly higher than that of sodium azide, and catechin as catechol reference. The reaction of catecholamines and singlet oxygen was further studied by ESR using 55-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trapping reagent and rose bengal as photosensitizer. DMPO-OH signal of epinephrine was significantly small compared to other catecholamines, catechin, and 4-methylcatechol as a reference compound and was as small as that of tyrosine. The signal formation was totally dependent on singlet oxygen, and the presence of catechol compounds. These results indicated that epinephrine is the most potent singlet oxygen quencher than other catecholamines, and the secondary amino group in its alkyl side chain could play a role in unique singlet oxygen quenching property of epinephrine

A Case of Nephrotic Syndrome with Nephrotoxicity Induced by Low-Dose Cyclosporin Treatment

We report a 3-year-old girl with steroid resistant nephrotic syndrome (NS) who developed nephrotoxicity by low-dose cyclosporin (CsA) treatment. Initial prednisolone (PSL) treatment and subsequent additional cyclophosphamide treatment were not successful in leading her into remission. The first renal biopsy finding revealed neither a glomerular nor interstitial change. CsA therapy was initiated in addition to ongoing glucocorticoid therapy at 6 months from the time of onset. Proteinuria disappeared 3 weeks later and the patient went into complete remission. After experiencing the first relapse, the patient was gradually weaned from CsA, and treatment continued with 30 to 50 ng/mL of trough concentration. No elevations of the serum creatinine, serum urea, serum potassium, excretion of urinary β2-microglobulin, or urinary N-acetyl-β-D-glucosaminidase were demonstrated in the follow-up. A second renal biopsy specimen obtained 1 year later showed a tubulo-interstitial change, containing tubular atrophy and interstitial fibrosis, both of which are consistent with the morphological change associated with CsA nephrotoxicity. A follow-up biopsy should be done in order to evaluate the CsA nephrotoxicity, regardless of the treatment dosage

Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood

The nutritional environment to which animals are exposed in early life can lead to epigenetic changes in the genome that influence the risk of obesity in later life. Here, we demonstrate that the fibroblast growth factor-21 gene (Fgf21) is subject to peroxisome proliferator-activated receptor (PPAR) α–dependent DNA demethylation in the liver during the postnatal period. Reductions in Fgf21 methylation can be enhanced via pharmacologic activation of PPARα during the suckling period. We also reveal that the DNA methylation status of Fgf21, once established in early life, is relatively stable and persists into adulthood. Reduced DNA methylation is associated with enhanced induction of hepatic FGF21 expression after PPARα activation, which may partly explain the attenuation of diet-induced obesity in adulthood. We propose that Fgf21 methylation represents a form of epigenetic memory that persists into adulthood, and it may have a role in the developmental programming of obesity

Current Status and Future Potential of Robotic Surgery for Gastrointestinal Cancer

　Robotic surgery has built on innovations in areas such as medical engineering and optical technology. Laparoscopic surgery has been successfully adapted for gastric, colon, and rectal cancer surgeries over the past two decades with numerous clinical trials showing oncological results comparable to those of open surgery. These trials have also shown that the laparoscopic approach shortens postoperative recovery time and decreases complication rates. Another advantage of minimally invasive techniques for the resection of gastric, colon, and rectal cancers is improved visualization of the surgical field. Despite the near absence of tactile feedback, robotic surgery has overcome many of the challenges inherent in laparoscopic surgery through features such as 3D vision, stable magnification, EndoWrist instruments, physiological tremor filtering, and motion scaling. Robotic surgery is not yet widely used in esophageal cancer surgery or in a pancreaticoduodenectomy for pancreatic cancer due to anatomical difficulties and the lack of a suitable approach.　Comparative studies of robotic and laparoscopic surgery have shown similar results in terms of perioperative management, oncologic evaluation, and functional outcomes. However, it is also true that the high cost and lack of tactile feedback in robotic surgery are major limitations in terms of current robotic technology becoming the worldwide standard for minimally invasive surgery. The future of robotic surgery will require cost reduction, the development of new platforms and technologies, the creation and validation of curricula and virtual simulators, and confirmation through appropriate randomized controlled clinical trials