豆腐凝固机理的研究

发现了在豆腐凝固过程中豆乳的pH随温度升高而下降,证明了二价金属离子引起豆乳pH下降的原因是与植酸盐、柠檬酸盐等发生络合反应所致,阐明了酸和盐凝固豆腐本质上的一致性。     

Gallium nitrate inhibits bone resorption and collagen synthesis in neonatal mouse calvariae.

Gallium nitrate (GN) is an agent used in the treatment of hypercalcemia. To more fully characterize the direct actions of GN on bone, we examined its effects on medium calcium, medium beta-glucuronidase (beta-GLU), and collagen synthesis in control and hormone-stimulated neonatal (4-6 days) mouse calvariae in vitro. GN (10 micrograms/ml) inhibited parathyroid hormone-stimulated (PTH; 1 nM) calcium release. A 24 h preincubation with 10 micrograms/ml of GN was required for complete inhibition; partial inhibition was seen with 12 h preincubation; 1, 3, or 6 h was inadequate. A dose-response study showed that with 24 h preincubation, 5, 3, and 1 microgram/ml of GN inhibited 81, 62, and 0% of PTH-induced calcium release. The effects of GN on the release of beta-GLU generally paralleled those on the release of calcium except that 10 micrograms/ml of GN stimulated beta-GLU release. Collagen synthesis was inhibited 50% by 3 micrograms/ml of GN, whereas noncollagen protein synthesis was unaffected. With PTH + GN no further decrease was observed. When GN was withdrawn from the medium after 24 h of preincubation, the inhibitory effect on calcium release and beta-GLU activity, but not on collagen synthesis, persisted through the 72 h of culture. GN also inhibited the resorption elicited by thyroxine (1 microM) and interleukin-1 beta (10 nM) but not by 1,25-dihydroxyvitamin D3 (30 pM). Our results indicate that GN is a powerful inhibitor of bone resorption in neonatal mouse calvariae even at low doses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Synthesis, tubulin binding, antineoplastic evaluation, and structure-activity relationship of oncodazole analogues

In an attempt to identify a soluble oncodazole analogue that could be easily formulated, a series of substituted oncodazoles was synthesized and evaluated for tubulin binding affinity, in vitro cytotoxicity against cultured mouse B-16 cells, and ability to prolong lifespan at the maximally tolerated dose in the P388 mouse leukemia model. Biological evaluation of all the isomeric methyloncodazoles demonstrated the thiophene 4'-position to be the only site of significant bulk tolerance, although substitution of this position with polar or charged functional groups abolished biological activity. Simple esters of the 4'-carboxymethyloncodazole were shown to have enhanced antitumor activity and tubulin binding affinity relative to oncodazole. Despite a failure of this study to identify a water-soluble oncodazole with antitumor activity, the structure-activity relationship developed led to a derivative with enhanced activity in the P388 leukemia model and facilitated the preparation of a biologically active photolabile analogue.     

Fluoxetine affects cytosolic cAMP,ATP, Ca2+ responses to forskolin,and survival of human ovarian granulosa tumor COV434 cells

Fluoxetine (FLX), a selective serotonin reuptake inhibitor antidepressant, exhibits various other mechanisms of action in numerous cell types and has been shown to induce cell death in cancer cells, paving the way for its potential use in cancer therapy. The aim of this study was to determine the off-target effects of the anti-depressant drug FLX, on the human ovarian granulosa tumor COV434 cells stimulated by forskolin (FSK), by measuring the real-time kinetics of intracellular cyclic AMP (cAMP), ATP level, cytoplasmic calcium ([Ca²⁺]_cyt) and survival of COV434 cells. We show that incubating COV434 cells with FLX (between 0.6 and 10 µM) induces a decrease in intracellular cAMP response to FSK, a drop in ATP content and stimulates cytoplasmic Ca²⁺ accumulation in COV434 cells. Only the highest concentrations of FLX (5–10 µM) diminished cell viability. The present report is the first to identify an action mechanism of FLX in human tumor ovarian cells COV434 cells and thus opening the way to potential use of fluoxetine as a complementary tool, in granulosa tumor treatments.     

Safety profile of snake antivenom (use) in Hong Kong – a review of 191 cases from 2008 to 2015

Introduction: The mainstay of treatment for significant envenoming from snakebites is antivenom. However, there is insufficient data regarding the safety of antivenom used in Hong Kong. We describe the incidence of hypersensitivity reactions from antivenom use and review the frequency and reasons for intensive care unit (ICU) admission.

Methods: The Hong Kong Poisons Information Centre database was reviewed. All patients given snake antivenom between 2008 and 2015 were included. Patient demographics, species of snake involved, details of antivenom used, treatment location, use of pre-treatment, reasons for ICU admission (where applicable) and details of early and late antivenom reactions were extracted.

Results: There were 191 patients who received snake antivenom. Most (93%) were treated with either the green pit viper antivenom from Thailand or the Agkistrodon halys antivenom from China. The incidences of early hypersensitivity reactions to green pit viper antivenom and Agkistrodon Halys antivenom were 4.7% and 1.4%, respectively. Most patients (69%) were managed in the ED observation ward or general ward. There were 59 patients managed in ICU, most (90%) of whom were admitted for close monitoring during antivenom administration. There were no cases of significant morbidity from antivenom administration. Eight patients (5.6%) had features suggestive of mild serum sickness.

Conclusions: The incidence of immediate hypersensitivity reaction to antivenom commonly used in Hong Kong is low. Majority of patients were managed safely in the emergency department observation ward or general ward. Serum sickness appears to be uncommon and possible cases presented with mild features.     

Trends and Patterns of Hepatocellular Carcinoma Treatment in Korea

Multiple therapeutic modalities are available for hepatocellular carcinoma (HCC) treatment. We aimed to evaluate the trends for HCC treatment in Korea. Recent trends and patterns in treatment modalities were assessed in HCC patients who first registered for the Health Insurance Review Assessment Service between 2008 and 2012. From 2009 to 2012, 57,690 patients were diagnosed with HCC. Transcatheter arterial chemoembolization (TACE) was the most common treatment modality for initial treatment. Curative treatment modalities like hepatic resection, liver transplantation, and local ablation therapy increased gradually. The 3 most common treatment modalities (hepatic resection, local ablation therapy, TACE) used after initial treatment in 2009 were studied. Following initial hepatic resection, 44.5% of patients required re-treatment. TACE was the most common modality (in 48.3% of cases), while 15.0% of patients received local ablation therapy. After local ablation therapy, 55.4% of patients were re-treated, wherein 45.0% of patients received TACE and 31.5% received local ablation therapy. Following initial TACE, 73.9% patients were re-treated, most commonly with TACE (57.7%) followed by local ablation therapy (12.8%). While there were no significant differences between the initial and re-treatment modalities, various multiple treatments followed the initial treatment. The treatment modalities were interchangeable.     

Canonical and noncanonical Wnts use a common mechanism to activate completely unrelated coreceptors

Wnt ligands signal through β-catenin and are critically involved in cell fate determination and stem/progenitor self-renewal. Wnts also signal through β-catenin-independent or noncanonical pathways that regulate crucial events during embryonic development. The mechanism of noncanonical receptor activation and how Wnts trigger canonical as opposed to noncanonical signaling have yet to be elucidated. We demonstrate here that prototype canonical Wnt3a and noncanonical Wnt5a ligands specifically trigger completely unrelated endogenous coreceptors-LRP5/6 and Ror1/2, respectively-through a common mechanism that involves their Wnt-dependent coupling to the Frizzled (Fzd) coreceptor and recruitment of shared components, including dishevelled (Dvl), axin, and glycogen synthase kinase 3 (GSK3). We identify Ror2 Ser 864 as a critical residue phosphorylated by GSK3 and required for noncanonical receptor activation by Wnt5a, analogous to the priming phosphorylation of low-density receptor-related protein 6 (LRP6) in response to Wnt3a. Furthermore, this mechanism is independent of Ror2 receptor Tyr kinase functions. Consistent with this model of Wnt receptor activation, we provide evidence that canonical and noncanonical Wnts exert reciprocal pathway inhibition at the cell surface by competition for Fzd binding. Thus, different Wnts, through their specific coupling and phosphorylation of unrelated coreceptors, activate completely distinct signaling pathways.     

Effects of Paecilomyces tenuipes cultivated in egg yolk on lipid metabolism in rats on a high fat-cholesterol diet

We investigated the effects of the fruiting bodies of cultivated Paecilomyces tenuipes grown on egg yolk (PTE) on lipid and antioxidant metabolisms. Forty 8-week-old male Sprague-Dawley rats were fed a high fat/high cholesterol diet (control) or a high fat/high cholesterol diet with 1%, 3%, or 5% PTE for 5 weeks. PTE was found to significantly lower plasma total lipid, total cholesterol, low-density lipoprotein cholesterol, and the atherogenic index, compared with the control. Hepatic total lipid and total cholesterol were also significantly lower than in the control group. The hypolipidemic activity of PTE was increased with increasing concentrations, and plasma lipid peroxidation was significantly lower in the 3% and 5% PTE groups than in the control or 1% PTE group. Plasma total radical trapping antioxidant potential, erythrocytic antioxidant enzyme, and leukocytic DNA damage were not significantly different among the groups. Our results indicate that P. tenuipes cultivated on egg yolk can improve lipid profiles and lipid peroxidation in rats fed a high fat/high cholesterol diet.     

Novel potent orally active multitargeted receptor tyrosine kinase inhibitors: synthesis, structure-activity relationships, and antitumor activities of 2-indolinone derivatives

The inhibition of receptor tyrosine kinases (RTKs) has become a successful approach in the development of anticancer agents. Many potent small-molecule kinase inhibitors have been discovered. We report herein a series of pyrrolo-fused-heterocycle-2-indolinone analogues as inhibitors of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and c-Kit. Among them, some pyrrolo-fused six- and seven-membered-heterocycle derivatives such as 9, 15, 23, and 25 are potent inhibitors of VEGFR, PDGFR, and c-Kit both enzymatically (<50 nM) and cellularly (<50 nM). Furthermore, compounds 9 and 25 possess favorable pharmacokinetic profiles and demonstrate good efficacies against human HT-29 cell colon tumor xenografts in nude mice. Further evaluations are in progress.