Current guidelines for management of chronic hepatitis B recommend treatment for patients presenting with elevated hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) >2 ؋ upper limit of normal (ULN) or histological evidence of liver disease. Retrospective analyses have demonstrated that significant hepatic necroinflammation and fibrosis were present in a substantial proportion of patients with ALT 1 to 2 ؋ ULN. To assess therapeutic efficacy in this clinical setting, we retrospectively examined treatment endpoints among the subset of nucleoside-naïve chronic hepatitis B (CHB) patients treated in phase 3 clinical trials of entecavir who had both screening and baseline serum ALT 1.3 to 2 ؋ ULN. A total of 1347 patients were randomized to treatment with entecavir or lamivudine. Three hundred thirty-six patients, constituting 25% of the total study population, had screening and baseline ALT 1.3 to 2 ؋ ULN. Clinically significant necroinflammation (Knodell necroinflammation score >7) was observed in 60% and 72% of hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients, respectively, whereas marked fibrosis (Ishak fibrosis score >4) was observed in 8% and 15% of HBeAg-positive and HBeAg-negative patients, respectively. Among entecavir-treated HBeAgnegative patients, the proportions of patients achieving histological improvement, HBV DNA <300 copies/mL, and ALT normalization were similar between patients with mildly elevated ALT and those with ALT >2 ؋ ULN. However, entecavir-treated HBeAg-positive patients with mildly elevated ALT had lower response rates for histological improvement, HBV DNA less than 300 copies/mL, ALT normalization, and HBeAg seroconversion than those with ALT greater than 2 ؋ ULN. Conclusion: This retrospective analysis demonstrated that HBeAg-negative CHB patients treated with entecavir responded similarly irrespective of baseline ALT level. However, HBeAg-positive patients with mildly elevated ALT responded less well to treatment with entecavir than did those with ALT greater than 2 ؋ ULN. (HEPATOLOGY 2010;51:1185-1189
Pereskia bleo, a leafy cactus, is a medicinal plant native to West and South America and distributed in tropical and subtropical areas. It is traditionally used as a dietary vegetable, barrier hedge, water purifier, and insect repellant and for maintaining health, detoxification, prevention of cancer, and/or treatment of cancer, hypertension, diabetes, stomach ache, muscle pain, and inflammatory diseases such as dermatitis and rheumatism. The aim of this paper was to provide an up-to-date and comprehensive review of the botanical characteristics, traditional usage, phytochemistry, pharmacological activities, and safety of P. bleo. A literature search using MEDLINE (via PubMed), Science direct, Scopus and Google scholar and China Academic Journals Full-Text Database (CNKI) and available eBooks and books in the National University of Singapore libraries in English and Chinese was conducted. The following keywords were used: Pereskia bleo, Pereskia panamensis, Pereskia corrugata, Rhodocacus corrugatus, Rhodocacus bleo, Cactus panamensis, Cactus bleo, Spinach cactus, wax rose, Perescia, and Chinese rose. This review revealed the association between the traditional usage of P. bleo and reported pharmacological properties in the literature. Further investigation on the pharmacological properties and phytoconstituents of P. bleo is warranted to further exploit its potentials as a source of novel therapeutic agents or lead compounds.
Recently, there has been considerable interest in a possible link between changes in brain polyunsaturated fatty acids, neural membrane phospholipid degradation, serotonergic neurotransmission, and depression. The present study aims to examine effects of antidepressants on lipids in different regions of the brain at individual molecular species level, using the novel technique of lipidomics. Balb/C mice received daily intraperitoneal (i.p.) injections of 10 mg/kg of the antidepressants maprotiline, fluoxetine and paroxetine for 4 wk. The prefrontal cortex, hippocampus, striatum and cerebellum were harvested, and lipid profiles compared to those of saline-injected mice. Treatment with maprotiline and paroxetine, but not fluoxetine, resulted in significant decreases in phosphatidylcholine (PC) species, PC36:1, PC38:3, PC40:2p, PC40:6, PC40:5, PC42:7p, PC42:6p and PC42:5p in the prefrontal neocortex. The decreases in phospholipids were accompanied by increases in lysophospholipid species, lysoPC16:0, lysoPC18:2 and lysoPC18:0 in the prefrontal cortex, indicating increase in phospholipase A2 activity and possible release of long-chain fatty acids. Maprotiline and paroxetine treatment also resulted in decreases in sphingomyelin and increases in several ceramide species in the prefrontal cortex. It is postulated that endogenous release of long-chain fatty acids may be related to the mechanism of action of maprotiline and paroxetine.
Background: Dysregulation of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) form the basis of immune-mediated inflammatory diseases. Vitex trifolia L. is a medicinal plant growing in countries such as China, India, Australia and Singapore. Its dried ripe fruits are documented in Traditional Chinese Medicine to treat ailments like rhinitis and dizziness. Its leaves are used traditionally to treat inflammation-related conditions like rheumatic pain. Objective: This study aimed to investigate the effects of V. trifolia leaf extracts prepared by different extraction methods (Soxhlet, ultrasonication, and maceration) in various solvents on cytokine production in human U937 macrophages, and identify phytoconstituents from the most active leaf extract. Methods: Fresh leaves of V. trifolia were extracted using Soxhlet, ultrasonication, and maceration in hexane, dichloromethane, methanol, ethanol or water. Each extract was evaluated for its effects on TNF-α and IL-1β cytokine production by enzyme-linked immunosorbent assay in lipopolysaccharide-stimulated human U937 macrophages. The most active extract was analyzed and further purified by different chemical and spectroscopic techniques. Results: Amongst 14 different leaf extracts investigated, extracts prepared by ultrasonication in dichloromethane and maceration in ethanol were most active in inhibiting TNF-α and IL-1β production in human U937 macrophages. Further purification led to the isolation of artemetin, casticin, vitexilactone and maslinic acid, and their effects on TNF-α and IL-1β production were evaluated. We report for the first time that artemetin suppressed TNF-α and IL-1β production. Gas chromatography-mass spectrometry analyses revealed the presence of eight other compounds. To the best of our knowledge, this is the first report of butylated hydroxytoluene, 2,4-di-tertbutylphenol, campesterol and maslinic acid in V. trifolia leaf extracts.
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