PubMed Health⌕ Search

Biomedical subjects

W Chong

Publications and source records attributed to W Chong.

14 recordsLinked to original sources
PubMed2006

An orally active cathepsin K inhibitor, furan-2-carboxylic acid, 1-{1-[4-fluoro-2-(2-oxo-pyrrolidin-1-yl)-phenyl]-3-oxo-piperidin-4-ylcarbamoyl}-cyclohexyl)-amide (OST-4077), inhibits osteoclast activity in vitro and bone loss in ovariectomized rats.

Human cathepsin K, a cysteine proteinase of the papain family, has been recognized as a potential drug target for the treatment of osteoporosis. The predominant expression of cathepsin K in osteoclasts has rendered the enzyme into a major target for the development of novel antiresorptive drugs. Now, we report the pharmacological properties of OST-4077 [furan-2-carboxylic acid (1-{1-[4-fluoro-2-(2-oxo-pyrrolidin-1-yl)-phenyl]-3-oxo-piperidin-4-ylcarbamoyl}-cyclohexyl)-amide] as a novel selective cathepsin K inhibitor. Human and rat cathepsin K were inhibited in vitro by OST-4077 with the IC50 values of 11 and 427 nM, respectively. OST-4077 suppressed bone resorption induced by rabbit osteoclasts (IC50, 37 nM) but did not affect bone mineralization or cellular alkaline phosphatase activity in MC3T3-E1 cells. Parathyroid hormone-induced bone resorption was inhibited in a dose-dependent manner in thyroparathyroidectomized rats gavaged with a single dose of OST-4077 (ED50, 69 mg/kg). When given orally twice daily for 4 weeks to 3-month-old ovariectomized (OVX) rats, OST-4077 dose-dependently prevented bone loss, as monitored by bone densitometry, ash content, and urinary excretion of deoxypyridinoline. No change in serum osteocalcin in the OVX rats by OST-4077 suggested that bone formation might not be affected by the agent. In summary, OST-4077 selectively inhibited bone resorbing activities of osteoclasts and prevented bone loss induced by estrogen deficiency but did not affect bone formation. OST-4077, an orally active selective human cathepsin K inhibitor, may have the therapeutic potential for the treatment of diseases characterized by excessive bone loss including osteoporosis.

Alkaline Phosphatase↗
PubMed2006

Thoracic ventral dural defect: idiopathic spinal cord herniation.

Thoracic ventral dural defect, and resultant idiopathic spinal cord herniation, is a rare but increasingly recognized cause of a chronic progressive thoracic myelopathy, particularly in middle-aged women. A neurosurgically confirmed case is presented, together with a review of the pathogenesis, clinical presentation, imaging features, treatment options and progress of this entity post-treatment.

Adult↗
PubMed2006

Symptomatic and asymptomatic carotid stenosis: just when we thought we had all the answers.

The management of symptomatic and asymptomatic carotid stenosis has been a hotly debated topic for decades. The publication of four randomized controlled trials of carotid endarterectomy has clarified many of the issues. Patients with symptomatic carotid stenosis >70% benefit most with an absolute risk reduction of 17% over 2 years with numbers needed to treat of 3-6, whereas in patients with asymptomatic carotid stenosis >60%, the absolute risk reduction is 1% per annum (numbers needed to treat = 14-17). There is doubt about the benefit in women >70 years of age with asymptomatic stenosis. Carotid angioplasty and stenting is in its infancy and may one day supplant carotid endarterectomy as the treatment of choice; however, currently indications for this procedure include participation in randomized controlled trials, surgically inaccessible stenosis, in patients with combined symptomatic carotid and symptomatic coronary artery disease or in patients with severe co-morbidities that preclude formal carotid endarterectomy.

Aged↗
PubMed2004

Subtypes of alpha1- and alpha2-adrenoceptors mediating noradrenergic modulation of spontaneous inhibitory postsynaptic currents in the hypothalamic paraventricular nucleus.

Noradrenergic inputs to the hypothalamic paraventricular nucleus (PVN) play important roles in the regulation of neuroendocrine and autonomic functions. Previous reports show that noradrenaline increases the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in a subpopulation of type II neurones, acting via alpha(1)-adrenoceptors (ARs), but reduces this frequency in most type I and another subpopulation of type II neurones, via alpha(2)-ARs on presynaptic GABA neurones. Here, we identified the subtypes of alpha-ARs mediating noradrenaline-induced increases and decreases in the sIPSC frequency of PVN neurones, by using slice patch recordings from PVN neurones. In both type I and II neurones, the noradrenaline-induced decrease in sIPSC frequency was completely blocked by BRL44408 (alpha(2A)-AR antagonist) at 1-3 micro M, which is approximately 1/100 of its equilibrium dissociation constant (pA(2) = 8.0), but not by prazosin (20-100 micro M, alpha(2B/C)-AR antagonist; pA(2) = 7.5). The effect of noradrenaline was mimicked by guanfacine (alpha(2A)-AR agonist) with an EC(50) of 0.1 micro M. In type II neurones, the noradrenaline-induced increase in sIPSC frequency was not blocked by any of the following antagonists: RS17053 (10 micro M, alpha(1A)-AR antagonist), BMY7378 (2 micro M, alpha(1D)-AR antagonist), prazosin (0.1 micro M, alpha(1)-AR antagonist; pA(2) = 10.5), or chloroethylclonidine (10 micro M, alpha(1B/D)-AR antagonist). However, the effect of noradrenaline was blocked by higher concentrations of prazosin (1 micro M) or RS17053 (100 micro M), suggesting the involvement of alpha(1L)-subtype, a low affinity form of alpha(1A)-ARs. Collectively, our results indicate that the alpha(2A)-, or alpha(1L)-ARs on the GABA neurones mediate the noradrenaline-induced decreases, or increases in the frequencies of the sIPSCs of PVN neurones, respectively.

Adrenergic alpha-Agonists↗
PubMed2002

Lack of bioequivalence of two oxytetracycline formulations in the rabbit.

Oxytetracycline (OTC) has been used for over 40 years in veterinary medical field. Various forms of oxytetracycline preparations have been marketed, but little information is available on the bioequivalence of OTC preparations. This study was conducted to evaluate the bioequivalence of two OTC powder preparations available in Korea. Fourteen rabbits were randomly allocated into two groups. During the first period, a dose (200 mg/kg) of reference product was orally administered to the rabbits in Group A and test product to those in Group B. After 7-day washout period the reference and test products were given in group B and A, respectively. Blood samples were drawn at 17 points during 48 hours after administration and plasma OTC concentrations were measured by using HPLC. The solution concentrations of OTC dissolved from two products were not significantly different in the dissolution test. The mean area under the curve (AUC0- infinity ) and peak plasma concentration (C(max)) values for test and reference OTCs were 7.22 +/- 3.90 and 11.04 +/- 7.37 microg h/ml, 1.11 +/- 0.65 and 1.85 +/- 1.15 microg/ml, respectively. The relative bioavailability and C(max) of test product to those of reference product was 65.4% and 60.0%, respectively. The ranges of AUC and C(max) of test drug compared to those of reference drug under 90% confidence limits were 27 104% and 28 91.5%, respectively. The results of statistical analysis indicate that the two pivotal pharmacokinetic parameters, AUC and C(max) of test product are not within the 20% of those of the reference, suggesting that the test OTC is not bioequivalent to the reference OTC.

Analysis of Variance↗
PubMed2001

A novel growth suppressor gene on chromosome 17p13.3 with a high frequency of mutation in human hepatocellular carcinoma.

Previous studies have shown that there is a high frequency of loss of heterozygosity (LOH) on chromosome 17p13.3 in hepatocellular carcinoma [HCC (M. Fujimori et al., Cancer Res., 51: 89-93, 1991; H. Nagai et al., Oncogene, 14: 2927-2933, 1997; V. Boige et al., Cancer Res., 57: 1986-1990, 1997; Z. Piao et al., Int. J. Cancer, 75: 29-33, 1998; and B. Charroux et al., J. Cell Biol., 148: 1177-1186, 2000)]. The minimum region of LOH on chromosome 17p13.3 in HCC has been defined within the region between D17S643 and D17S1574. Moreover, D17S926 in the minimum region of LOH has the highest frequency of LOH, and its sequencing analysis has been accomplished. In this region, 6 of 13 novel genes have been characterized (X. Zhao, D. Wan, M. He, Yu. Ye, Yi. He, L. Han, M. Guo, Y. Huang, W. Qin, M-W. Wang, W. Chong, J. Chen, L. Zhang, N. Yang, B. Xu, M. Wu, L. Zuo, and J. Gu. A high frequency LOH region on chromosome 17p13.3 in human HCC with densely clustered genes identified, submitted for publication). Here we describe the cloning and characterization of one of these novel genes, designated HCC suppressor 1 (HCCS1), located at this region. HCCS1 had 18 exons, and its full-length cDNA was 2.0 kb. The protein expression product of HCCS1 was located in mitochondria. HCCS1 had a high frequency of mutations in HCC samples, whereas no alteration has been found in matched noncancerous liver tissues. Immunohistochemistry revealed a significantly higher expression of HCCS1 in the noncancerous liver tissues (33 of 35 samples) than in the HCC samples (2 of 35 samples). Transfection of HCCS1 cDNA into the HCC cell line remarkably reduced the efficiency of its colony formation and inhibited tumor growth in nude mice. Taken together, these findings strongly suggest a potential role of HCCS1 as a HCC putative suppressor gene.

3T3 Cells↗
PubMed2001

Activation of metabotropic glutamate receptors inhibits GABAergic transmission in the rat subfornical organ.

Glutamate is known to increase neuronal excitability in the subfornical organ, a circumventricular organ devoid of the blood-brain barrier. To understand the synaptic mechanism of neuronal excitation by glutamate in this nucleus, we examined the effects of glutamate on GABAergic spontaneous inhibitory postsynaptic currents recorded from subfornical organ neurons in the rat brain slice. The baseline frequency, amplitude and decay time-constant of such spontaneous synaptic currents were 5.60 Hz, 119 pA and 17.3 ms, respectively. Glutamate (10-1000 microM) selectively inhibited the frequency of spontaneous GABAergic inhibitory postsynaptic currents (half-maximal effective concentration=47 microM) with little effects on their amplitudes and decay time constants. The inhibitory effect of glutamate on the frequency of spontaneous GABAergic postsynaptic currents was not blocked by tetrodotoxin (1 microM), or by the antagonists of ionotropic glutamate receptors. In contrast, such inhibitory effect of glutamate was mimicked by general or group II selective metabotropic glutamate receptor agonists such as DCGIV (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (half-maximal effective concentration=112 nM), but not by the agonists for group I or group III metabotropic glutamate receptors. Under current clamp mode, glutamate reduced the frequencies of spontaneous inhibitory postsynaptic potentials and action potentials in subfornical organ neurons. Our data indicate that glutamate decreases the frequency of spontaneous inhibitory postsynaptic currents by acting on the group II metabotropic glutamate receptors on axonal terminals in the subfornical organ. From these results we suggest that the glutamate-induced modulation of tonic GABAergic inhibitory synaptic activity can influence the excitability of subfornical organ neurons.

Animals↗
PubMed1997

Unsuspected thyrotoxicosis and hyperemesis gravidarum in Asian women.

This report describes three women with hyperemesis gravidarum caused by previously undiagnosed thyrotoxicosis. All three women were eight weeks pregnant and only one woman had typical features of thyrotoxicosis. Hyperemesis could not be controlled by anti-emetics. The patients were successfully treated with antithyroid drugs. Anti-thyroid treatment does not need to be continued once resolution of symptoms and thyrotoxicosis have occurred.

Adult↗
PubMed1991

Conditions affecting direct gene transfer into rodent muscle in vivo.

This report extends our previous findings that mouse muscle cells in situ can take up naked DNA injected intramuscularly in vivo. Various conditions such as needle type, speed of injection, volume of injection fluid, tonicity of injection fluid, type of solute, type of muscle, physiologic condition of the muscle and age of the animals were appraised for their effect on the levels of luciferase activity expressed from the pRSVL plasmid. Specific conditions such as the use of normal saline as an injection fluid increased the efficiency of expression. The implantation of DNA pellets was an effective way to deliver DNA to muscle, especially for smaller muscle groups. Also, newborn and adult rat muscles expressed plasmid DNA delivered intramuscularly.

Aging↗
PubMed1991

Direct gene transfer and expression into rat heart in vivo.

We found previously that genes injected into skeletal muscle can be taken up by myofibers and expressed. In the present study we found that myocardial cells can also express a variety of reporter genes injected into myocardium as efficiently as skeletal myofibers, while the cells of several other tissues cannot. The inability of tissues other than striated muscle to express injected DNA is not due to technical difficulties of injection because injected DNA was detected in these other tissues by PCR analysis. These results suggest that skeletal and cardiac muscle cells have unique features such as T tubules that may play a critical role in DNA uptake. Expression in cardiac muscle was stable for only two weeks, possibly because of an immune response against the transfected cells. The ability to directly transfer genes into myocardial cells raises the possibility of gene therapy for both acquired and genetic heart diseases.

Animals↗
PubMed1990

Direct gene transfer into mouse muscle in vivo.

RNA and DNA expression vectors containing genes for chloramphenicol acetyltransferase, luciferase, and beta-galactosidase were separately injected into mouse skeletal muscle in vivo. Protein expression was readily detected in all cases, and no special delivery system was required for these effects. The extent of expression from both the RNA and DNA constructs was comparable to that obtained from fibroblasts transfected in vitro under optimal conditions. In situ cytochemical staining for beta-galactosidase activity was localized to muscle cells following injection of the beta-galactosidase DNA vector. After injection of the DNA luciferase expression vector, luciferase activity was present in the muscle for at least 2 months.

Animals↗
PubMedDate not supplied

Removal of stones from the bile duct at ERCP without sphincterotomy.

The main risks associated with endoscopic stone removal arise from the sphincterotomy that is performed to facilitate stone extraction. The complication rate may be higher when the bile duct is not dilated. Between January 30, 1990, and March 30, 1993, we attempted to remove stones up to 8 mm in diameter through the intact papilla, without performing sphincterotomy, in 24 patients. Nine patients underwent balloon dilation of the sphincter or of a low duct stricture to facilitate stone removal. All patients were treated successfully and are well at follow-up. Two patients (one having had balloon dilation of the sphincter) had mild pancreatitis that required 2 days in the hospital. During the same period, 215 patients were treated for duct stones 8 mm or less through a standard sphincterotomy. Complications occurred in 11 of these patients: five episodes of pancreatitis, three infections, one perforation, and two other complications. Although these two groups of patients are not directly comparable, it appears that selected stones can be extracted from the bile duct without sphincterotomy with relative safety. This technique should be studied further, especially in younger persons where sphincter preservation may be desirable.

Adolescent↗