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Biomedical subjects

C Y Hong

Publications and source records attributed to C Y Hong.

At least 37 records · Page 2Linked to original sources

Myopia and night lighting in children in Singapore.

AIM: To examine the role of night time lighting and myopia in children in Singapore METHODS: A cross sectional study was conducted on 1001 children in two Singapore schools. Cycloplegic refraction and A-scan biometry measurements were made in both eyes. A detailed questionnaire was completed by the parents to obtain information on night time lighting, near work activity, educational and demographic factors. RESULTS: There was no difference in myopia prevalence rates in children exposed to night time light (33.1%) compared with children who slept in the dark (31.4%) before age 2. In addition, vitreous chamber depth was not related to night light (p = 0.58) before age 2. These results remained even after controlling for near work. CONCLUSION: Myopia is not associated with night light in Asian populations.

Anterior Chamber↗

Sensitization of a tumor, but not normal tissue, to the cytotoxic effect of ionizing radiation using Panax notoginseng extract.

The aim of the present study was to investigate any sensitization effect of the Panax notoginseng extract (PNE) and the purified Saponin (Rb1) on the radiation response of an experimental tumor (KHT sarcoma) in mice, in comparison with any effects on a normal tissue (bone marrow). PNE at a concentration of 0.1-100 mg/kg produced an increase in tumor radiosensitivity. The sensitization effect was maximal at 10 mg/kg and at 30 minutes after injection. Higher doses were toxic to the bone marrow stem cells. Similarly Rb1 at a concentration 0.001 to 1 mg/kg also produced an increase in tumor radiosensitivity, with maximum effect at 1 mg/kg. Higher doses were not toxic to the bone marrow stem cells in this case. Radiosensitization factors were calculated as ratios of D0 (the radiosensitivity parameter), and these were highly significant for the tumor and very similar for both compounds at the doses used, namely 1.18-1.19. There was no significant effect for bone marrow stem cells (sensitization factors of 0.99 +/- 0.01 for both compounds). The differential effect on tumor, and the magnitude of the radiosensitization, suggest that further purified or synthetic versions of this extract may be useful not only in vascular-related diseases but also in cancer therapy.

Animals↗

Matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 gene expressions and their differential regulation by proinflammatory cytokines and prostaglandin in nasal polyp fibroblasts.

Chronic inflammation of the paranasal sinus leads to nasal polyp (NP) formation. In this study, we investigated the effect of stimulation of the proinflammatory cytokines interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha) and prostaglandin (PG) E2 on the production of messenger RNA (mRNA) of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-I (TIMP-1) in nasal polyp fibroblasts (NPFs) and nasal mucosa fibroblasts (NFs). The mRNAs of IL-1alpha, TNF-alpha, MMP-1, and TIMP-1 in 40 surgical specimens of NPs were studied by in situ hybridization to corroborate the in vitro findings. The results indicated a significant amount of constitutive MMP-1 mRNA in NPFs and cytokine-induced MMP-1 steady-state mRNAs in NFs. The effect of stimulation of cytokines on TIMP-1 mRNA synthesis was unremarkable in NPFs and NFs. Exogenous PGE2 enhanced cytokine-stimulated MMP-1 mRNA synthesis in NPFs. In situ hybridization revealed that cells expressing MMP-1 and TIMP-1 mRNAs (primarily plasma cells, fibroblasts, and endothelial cells) gathered around areas with loose stroma, suggestive of rapid extracellular matrix degradation. These data suggest that the pathogenesis of nasal polyposis could be related to production of MMP-1 and consequent promotion of matrix collagenolysis.

Cytokines↗

Hemodynamic effects of synephrine treatment in portal hypertensive rats.

Synephrine, a sympathomimetic alpha1-adrenoceptor agonist, has been shown to induce dose-dependent portal hypotensive effects after acute intravenous infusion. The present study was undertaken to investigate the hemodynamic effects of 8-day administration of synephrine in portal hypertensive rats. Portal hypertension was induced by either partial portal vein ligation (PVL) or bile duct ligation (BDL). Portal hypertensive rats were allocated into one of two groups: vehicle group (0.1 N HCl, 0.5 ml/12 h) or synephrine group (1 mg/kg per 12 h), with 7 rats in each group. Synephrine or vehicle was administered by gavage into PVL and BDL rats for 8 consecutive days. Systemic as well as splanchnic hemodynamic parameters were measured thereafter. Synephrine significantly ameliorated the hyperdynamic state in both PVL and BDL rats. The portal venous pressure in PVL and BDL rats (-13.5% and -10.1%, respectively), portal tributary blood flow (-19.5% and -20.4%) and cardiac index (-12.1% and -18.8%) were significantly reduced, while mean arterial pressure (10.4% and 23.4%) and systemic (26.3% and 51.0%) as well as portal territory (47.1% and 67.7%) vascular resistance were enhanced by treatment of synephrine as compared with vehicle treatment. Our results showed that eight-day administration of synephrine exerted beneficial hemodynamic effects in two models of portal hypertensive rats.

Adrenergic alpha-Agonists↗

Hemodynamic effects of Salvia miltiorrhiza on cirrhotic rats.

Salvia miltiorrhiza (Sm) administration has been shown to reduce hepatic fibrosis in rats. We investigated the hemodynamic effects of Sm on bile duct ligated (BDL) rats. Hemodynamic, histological, and vascular contractile studies were conducted in rats 4 weeks after bile duct ligation. An aqueous extract of Sm (0.2 g twice per day) or vehicle was administered for 4 weeks to BDL rats. Sm treatment in BDL rats significantly reduced histological grades of fibrosis and ameliorated the portal hypertensive state (including portal venous pressure, superior mesenteric artery blood flow, cardiac index, and total peripheral resistance) as compared with vehicle treatment. Moreover, Sm treatment enhanced the vascular sensitivity of mesenteric arteries to phenylephrine in BDL rats. Sm treatment had no effect on plasma biochemical profiles of either BDL or normal rats. Our results suggest that 4-week Sm treatment ameliorates the portal hypertensive state in BDL rats.

Animals↗

Norcantharidin-induced post-G(2)/M apoptosis is dependent on wild-type p53 gene.

Norcantharidin (NCTD), a synthetic analogue of phosphatase type 2A inhibitors, cantharidin, was shown to have limited effects in treating human and animal tumors. The tumor cell killing mechanisms by norcantharidin, however, remain unclear. In this report, we wished to investigate the mechanisms of norcantharidin-mediated cytotoxicity. Effort was made to investigate whether norcantharidin exerted its cytotoxicity through a p53-dependent or -independent mechanism. RT-2 (wtp53) and U251 (mutant p53) glioblastoma cell lines were exposed to norcantharidin at different dosages. Time-course fluorescent-activated cell sorting (FACS) analysis showed that high doses of norcantharidin arrested the cells at the G(2)/M phase and subsequent post-G(2)/M apoptosis in RT-2 cell line. In comparison, the U251 cell line was found resistant to norcantharidin-induced cytotoxicity. Restoring wild-type p53 gene function in the U251 cell line after adenoviral infections induced tumor cell cytotoxicity after exposure to norcantharidin. These results showed that norcantharidin kills tumor cells efficiently corresponding to their endogenous p53 gene status. The results also showed the feasibility of using adenoviral p53 gene therapy to enhance chemosensitivity of tumor cells to norcantharidin.

Antineoplastic Agents↗

Direct liquid chromatographic enantiomer separation of new fluoroquinolones including gemifloxacin.

The enantiomers of gemifloxacin mesylate (formerly LB20304a), a new fluoroquinolone compound with potent in vitro and in vivo antibacterial profile were resolved on a commercially available Crownpak CR chiral stationary phase (CSP). All of the fluoroquinolones, including gemifloxacin used in this study, were well enantioseparated on Crownpak CR(+) column. These results are the first reported for the direct separation of the enantiomers of quinolones on chiral crown ether coated Crownpak CR CSP. The behavior of chromatographic parameters by the change of mobile phase additives for the resolution of gemifloxacin was investigated. Also, the effect of structural change of gemifloxacin on chiral recognition was described.

Anti-Infective Agents↗

Expression of p16(INK4A) induces dominant suppression of glioblastoma growth in situ through necrosis and cell cycle arrest.

Tumor suppressor genes may represent an important new therapeutic modality in the treatment of human glioblastoma (GBM). p16(INK4A) is a tumor suppressor gene with mutation and/or deletion found in many human tumors, including glioblastomas, melanoma, and leukemias. RT-2 rat GBM cell line was used to investigate if the p16 gene induces dominant suppression of glioblastoma growth. Close to 100% of tumor cells were infected by high titer pCL retrovirus encoding the full-length human p16 cDNA at 5 m.o.i. Infected cells showed a 98% reduction in colony forming assay and a 60% reduction in growth curves in vitro compared to vector control. Exogenous overexpression of p16 induced hypophosphorylation of Rb protein by Western blot analysis. Intracranial injection of p16-infected tumor cells into syngeneic rats resulted in a 95% reduction in tumor volume compared to the controls. Intratumoral injection of p16 retrovirus resulted in tumor necrosis and prominent human p16 transgene expressions. Proliferation marker PCNA was not detected in these human p16-expressed RT-2 tumor cells, suggesting the cells were unable to enter into S phase after p16 expression. In addition, direct repeat intracranial injections of p16 retrovirus prolonged animal survival 3.2-fold compared to the controls (48.4 +/- 13.4 vs 15.0 +/- 2.1 days, p < 0.001). Two out of ten rats were found with dormant tumors at day 60 after p16 retrovirus injection. These results showed that p16 is effective in inhibiting GBM growth in situ. The mechanisms of tumor growth reduction and necrosis in vivo might be due to G1 arrest triggered by p16 expression.

Animals↗

Synthesis and antibacterial activity of new carbapenems containing isoxazole moiety.

The synthesis and biological activity of a series of new 1beta-methylcarbapenems 1a-g containing 5'-isoxazolopyrrolidin-3'-ylthio derivatives as C-2 side chain are described. Most compounds exhibited potent and well-balanced antibacterial activity as well as high stability to DHP-I comparable to that of meropenem. 1e and 1c showed the best combination of antibacterial activity and stability to DHP-I, respectively.

Anti-Bacterial Agents↗

Induction of the c-jun protooncogene expression by areca nut extract and arecoline on oral mucosal fibroblasts.

To investigate the mechanisms of areca quid (AQ)-induced carcinogenesis, expression of c-fos and c-jun protooncogenes was examined in human oral mucosal fibroblasts after exposure to areca nut extracts (ANE) or arecoline. We found that treatment of cells with 200 microg/ml ANE or 10 microg/ml arecoline for 1 h induced about three-fold increase in c-jun mRNA levels. This increase was transient and the level of c-jun mRNAs returned rapidly to control levels thereafter. However, ANE and arecoline did not induce c-fos mRNA expression at detectable levels. During AQ chewing, oral mucosal cells are continuously stimulated by ANE and arecoline. Persistent induction of the c-jun protooncogene by ANE and arecoline may be one of the mechanisms in the carcinogenesis of oral squamous cell carcinoma in Taiwan. Furthermore, we observed that pre-incubation of cells with either N-acetyl-cysteine [a glutathione (GSH) precursor] or L-buthionine-S,R-sulfoximine (a specific inhibitor of GSH biosynthesis) had a minimal effect on arecoline-induced c-jun expression. Therefore, arecoline-induced c-jun expression is independent of GSH depletion.

Areca↗

Intravenous pretreatment with magnolol protects myocardium against stunning.

Magnolol, an antioxidant, has been reported to possess various protective effects on the cardiovascular system. However, its effect on myocardial stunning has not been elucidated. The purpose of this study was to investigate the antistunning effect of magnolol by evaluating the recovery of regional myocardial function after 10-minute coronary artery occlusion in anesthetized, open-chest rabbits. There was no significant hemodynamic change after intravenous infusion of magnolol. Systolic wall thickening fraction (WThF) measured with an epicardial Doppler sensor in animals pretreated with normal saline and vehicle solution remained significantly depressed (60 +/- 7% and 77 +/- 4% of baseline WThF, respectively) 3 hours after coronary artery reperfusion (CAR). Pretreatment with magnolol (10(-7) and 10(-6) g/kg, intravenous infusion) significantly enhanced the recovery of systolic wall thickening fraction (98 +/- 1 and 99 +/- 1% of baseline WThF, respectively) 60 minutes after CAR. This study demonstrated that intravenous pretreatment with magnolol protected myocardium against stunning.

Animals↗

Immunolocalization of macrophages and transforming growth factor-beta 1 in induced rat periapical lesions.

Apical periodontitis was induced in Wistar rats by exposing the pulp chamber of right mandibular first molars to the oral environment. Animals were killed 0, 5, 10, 15, 20, 30, 60, and 80 days after lesion induction. Microradiographic and automated image analysis showed that the lesions expanded significantly in a time-dependent manner from day 0 to day 20 (0.039 mm2/day, p < 0.05, active phase) and stabilized thereafter (chronic phase). A linear regression test revealed a positive correlation between the numbers of ED-1 positive macrophage per microscopic high power field and the periapical lesion size during the active phase (r = 0.98, p < 0.01). Immunohistochemical studies showed that transforming growth factor-beta 1 positive macrophages distributed around the root apex and areas showing bone resorption during active lesion phase, whereas TGF-beta 1-positive osteoblasts were detected during the chronic stage (days 30, 60, and 80 after pulp exposure). Histologically TGF-beta 1 positive osteoblasts possessed a large, round nucleus as well as an abundant cytoplasm and located in close vicinity to areas exhibiting reparative bone formation. These results suggest that macrophages may play important role(s) in the initiation and development of periapical lesions and TGF-beta 1 may play dual roles in both bone resorption and deposition in induced rat periapical lesions.

Acute Disease↗

Magnolol attenuates peroxidative damage and improves survival of rats with sepsis.

Reactive oxygen species and peroxidative damage are implicated in the pathophysiology of sepsis. Magnolol is a compound extracted from the Chinese medicinal herb Magnolia officinalis and has multiple pharmacological effects, notably antioxidant functions. To determine whether magnolol can modulate the course of sepsis, survival rate and biochemical parameters were analyzed in rats with sepsis with various treatment protocols. Magnolol at doses ranging from 10(-9) g/kg to 10(-5) g/kg was administered either before or after induction of sepsis by cecal ligation and puncture. Magnolol did not modulate the course of sepsis induced by two cecal punctures. When one cecal puncture was performed, a moderately evolving type of sepsis was induced, and the survival rate of affected rats was significantly improved by pretreatment with 10(-7) g/kg magnolol. The beneficial effect was partially retained if magnolol was administered 6 hours after onset of sepsis when a higher dose (10(-5) g/kg) was used. The intensity of lipid peroxidation in plasma, liver, and lung of septic rats was also attenuated in a treatment-dependent manner. Magnolol at this dose range exerted these beneficial effects probably through its antioxidant efficacy. These significant results may suggest magnolol as a candidate agent for the treatment of sepsis.

Animals↗

Effect of magnolol on coronary vascular resistance in rabbits: measurement with pulsed Doppler velocimetry.

BACKGROUND AND PURPOSE: Magnolol is an active component purified from Magnolia officinalis that has been reported to protect the myocardium against infarction and reperfusion injury. The purpose of this study was to investigate the effect of magnolol on the coronary circulation and to determine whether a change in coronary vascular resistance could be the mechanism underlying its myocardial protective effect. METHODS: Male New Zealand white rabbits were anesthetized. A 3-mm suction-type pulsed Doppler velocimetry probe was applied to the proximal part of the left anterior descending coronary artery after median sternotomy. The 39 rabbits received intravenous injection of either vehicle (n = 5), magnolol (10(-6) g/kg, n = 6; 10(-5) g/kg, n = 5; 10(-4) g/kg, n = 5), or nitroglycerin (10(-5) g/kg, n = 6; 10(-4) g/kg, n = 6; 10(-3) g/kg, n = 6). The effects of magnolol and nitroglycerin on coronary vascular resistance were compared. RESULTS: Magnolol did not change blood pressure or coronary blood flow velocity. However, at a dose of 10(-4) g/kg, it decreased coronary vascular resistance significantly more than vehicle (88 +/- 1% vs 95 +/- 1% of baseline coronary vascular resistance, p < 0.001). Nitroglycerin increased coronary blood flow velocity and decreased coronary vascular resistance in a dose-dependent manner (p < 0.01). CONCLUSIONS: Magnolol reduced coronary vascular resistance in anesthetized, open-chest rabbits only at a high concentration. Its effect was modest compared with that of nitroglycerin. Since magnolol protects the myocardium at relatively low doses, coronary vasodilatation is unlikely to be the underlying mechanism responsible for its myocardial protective effects.

Animals↗

N-substituted-3-arylpyrrolidines: potent and selective ligands at serotonin 1A receptor.

3-Arylpyrrolidines are synthesized through the coupling of N-benzyl-3-(methanesulfonyloxy)pyrrolidine with diarylcuprates. Pharmacological evaluation of a series of N-substituted-3-arylpyrrolidines toward several neurotransmitter receptors indicated that some of them are good ligands for serotonin 1A receptor. Particularly, N-[(N-saccharino)butyl]pyrrolidines were found to be potent and selective ligands. A preliminary biological evaluation for several selected compounds indicated that they are potentially effective antianxiety and antidepressant agents.

Animals↗

Measurement and pharmacokinetic study of tetramethylpyrazine in rat blood and its regional brain tissue by high-performance liquid chromatography.

We used a rapid, sensitive and reliable high-performance liquid chromatographic method for the determination of tetramethylpyrazine in rat brain tissue and plasma. The lower limit of quantification in plasma and brain tissue was 0.1 microgram/ml and 0.1 microgram/g, respectively, and only a small amount of plasma (100 microliters) or brain tissue (100 micrograms) was required for analysis. The decline in the concentration of tetramethylpyrazine in plasma was generally two-exponential at a dose of 2, 5, or 10 mg/kg administered intravenously. Concentrations of tetramethylpyrazine in various regions of the brain (cerebral cortex, brainstem, striatum, hippocampus, cerebellum and midbrain) were not significantly different at 15 min following drug administration (10 mg/kg, i.v.). In additional analysis, mean concentration of the tetramethylpyrazine in rat plasma was approximately five-times greater than the drug in brain tissue.

Animals↗

Synthesis and biological activities of C-2, N-9 substituted 6-benzylaminopurine derivatives as cyclin-dependent kinase inhibitor.

In this study, C-2, N-9 substituted 6-benzylaminopurine derivatives were synthesized and their inhibitory effects on cyclin-dependent kinase (CDK2) were evaluated. The effect of substituents at the C-2 and N-9 positions of substituted purine was investigated. Among the compounds tested, compound 7b-iii (6-benzylamino-2-thiomorpholinyl-9-isopropylpurine) was the most active inhibitor (IC50 = 0.9 microM). Compound 7b-iii showed 10-fold higher activity compared to olomoucine and almost the same activity as roscovitine. Results from structure-activity relationship studies should allow the design of more potent and selective CDK inhibitors, which may provide an effective therapy for cancer or other CDK dependent diseases.

Antineoplastic Agents↗