Melatonin protects against organ ischemia; this effect has mainly been attributed to the antioxidant properties of the indoleamine. This study examined the cytoprotective properties of melatonin against injury to the liver caused by ischemia/reperfusion (I/R). Rats were subjected to 60 min of ischemia followed by 5 hr of reperfusion. Melatonin (10 mg/kg) or the vehicle was administered intraperitoneally 15 min before ischemia and immediately before reperfusion. The serum aminotransferase activity and lipid peroxidation levels were increased markedly by hepatic I/R, which were suppressed significantly by melatonin. In contrast, the glutathione content, which is an index of the cellular redox state, and mitochondrial glutamate dehydrogenase activity, which is a maker of the mitochondrial membrane integrity, were lower in the I/R rats. These decreases were attenuated by melatonin. The rate of mitochondrial swelling, which reflects the extent of the mitochondrial permeability transition, was higher after 5 hr of reperfusion but was attenuated by melatonin. Melatonin limited the release of cytochrome c into the cytosol and the activation of caspase-3 observed in the I/R rats. The melatonin-treated rats showed markedly fewer apoptotic (TUNEL positive) cells and DNA fragmentation than did the I/R rats. These results suggest that melatonin ameliorates I/R-induced hepatocytes damage by inhibiting the level of oxidative stress and the apoptotic pathway. Consequently, melatonin may provide a new pharmacological intervention strategy for hepatic I/R injuries.

A design for omnidirectional high reflectors with quarter-wave dielectric stacks in the optical telecommunication band that uses conventional optical thin-film design theory is described. The omnidirectional bandwidth is derived in units of wavelength and investigated as a function of its high- and low-refractive-index values in the near infrared. The results show that the high refractive index should be larger than 2.26 for an omnidirectional high reflector and that the low refractive index for maximum onmidirectional bandwidth should be approximately 1.5. It is shown that one can design broad-bandwidth omnidirectional high reflectors for S, C, and L bands for optical telecommunication simply by connecting the band edges of omnidirectional high reflectors.

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Abstract. This study examined the effects of gomisin A, a lignan compound from Schisandra fructus, on D-galactosamine (GalN) and lipopolysaccharide (LPS)-induced hepatic apoptosis and liver failure. Mice were given an intraperitoneal injection of GalN (700 mg /kg) / LPS (10 µg/ kg). Gomisin A (25, 50, 100, and 200 mg / kg) was administered intraperitoneally 1 h before the GalN / LPS injection. The liver injury was assessed biochemically and histologically. GalN/ LPS increased the serum aminotransferase levels and lipid peroxidation but decreased the reduced glutathione level. The pretreatment with gomisin A attenuated these changes in a dose-dependent manner. The survival rate of the gomisin A group was significantly higher than that of the control. The mitochondria isolated after the mice had been injected with GalN / LPS were swollen, which was attenuated by the gomisin A pretreatment. The elevation of serum tumor necrosis factor-α and activation of caspase-3 were observed in the GalN / LPS group, which was attenuated by gomisin A. The gomisin A-pretreated groups showed significantly fewer apoptotic (TUNEL-positive) cells and DNA fragmentation as compared with the GalN / LPS mice. The liver protection afforded by gomisin A is the result of the reduced oxidative stress and its antiapoptotic activity.

Background-Ocular damage in leprosy is due either to nerve damage or infiltration by mycobacteria. There is currently little information about the magnitude and nature of incident ocular pathology in cured leprosy patients. This information would increase our understanding of the pathophysiology of ocular involvement in leprosy and help in developing programmes to address the eyecare needs of leprosy patients who have been released from treatment. The cumulative incidence of leprosy related ocular pathology and cataract was measured during an 11 year follow up period in cured leprosy patients released from treatment in Korea. Conclusion-This study demonstrates that leprosy related ocular pathology progresses in some patients even after they are cured mycobiologically. The progressive leprosy related lesions are the result of chronic nerve damage; ocular lesions due to infiltration by Mycobacterium leprae did not develop. Based on the factors found to be associated with development of the most visually significant findings (posterior synechia, keratitis, and cataract) certain patients should be targeted at discharge for active follow up eye care. We suggest that patients with lagophthalmos (even in gentle closure), trichiasis, small pupils, and posterior synechiae should be screened regularly for the development of lagophthalmos in forced closure, keratitis, and cataract. (Br J Ophthalmol 2000;84:817-821) Methods-In

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Stem cells are poorly permissive to non-viral gene transfection reagents. In this study, we explored the possibility of improving gene delivery into human embryonic (hESC) and mesenchymal (hMSC) stem cells by synergizing the activity of a cell-binding ligand with a polymer that releases nucleic acids in a cytoplasm-responsive manner. A 29 amino acid long peptide, RVG, targeting the nicotinic acetylcholine receptor (nAchR) was identified to bind both hMSC and H9-derived hESC. Conjugating RVG to a redox-sensitive biodegradable dendrimer-type arginine-grafted polymer (PAM-ABP) enabled nanoparticle formation with plasmid DNA without altering the environment-sensitive DNA release property and favorable toxicity profile of the parent polymer. Importantly, RVG-PAM-ABP quantitatively enhanced transfection into both hMSC and hESC compared to commercial transfection reagents like Lipofectamine 2000 and Fugene. ∼60% and 50% of hMSC and hESC were respectively transfected, and at increased levels on a per cell basis, without affecting pluripotency marker expression. RVG-PAM-ABP is thus a novel bioreducible, biocompatible, non-toxic, synthetic gene delivery system for nAchR-expressing stem cells. Our data also demonstrates that a cell-binding ligand like RVG can cooperate with a gene delivery system like PAM-ABP to enable transfection of poorly-permissive cells.

DNA-PCR and reverse transcription (RT)-PCR for the 18-kDa protein of Mycobacterium leprae were used to examine the efficacy of multi-drug therapy (MDT) in leprosy. MDT was administered for 0-24 months. Fourteen (63.6%) of 22 patients showed positive PCR results after treatment for 12 months and the positive results decreased to 30% after 24 months of MDT. These results did not correlate with the bacterial index (BI) or the IgM antibody titre for the phenolic glycolipid (PGL)-1. One-dimensional densitometric analysis of agarose gels from PCR from the longitudinal study showed a gradual reduction of the 360-bp band after 12-24 months of MDT. RT-PCR for mRNA of the 18-kDa protein successfully tracked bacterial RNA changes in the biopsies and confirmed a decrease in the RNA of M. leprae in patients after MDT for 12 months. Thus, DNA-and RT-PCR for the 18-kDa protein of M. leprae are effective in assessing the efficacy of MDT for leprosy.