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Biomedical subjects

S H Chung

Publications and source records attributed to S H Chung.

At least 19 recordsLinked to original sources
PubMed2001

Brownian dynamics study of an open-state KcsA potassium channel.

Three-dimensional Brownian dynamics simulations are used to study conductance of the KcsA potassium channel using the known crystallographic structure. Employing an open-state channel created by molecular dynamics simulations, current-voltage and current-concentration curves broadly consistent with experimental measurements are obtained. In the absence of an applied potential, the channel houses three potassium ions at positions that are in close agreement with X-ray diffraction maps.

Bacterial Proteins↗
PubMed2001

Comparisons between white ginseng radix and rootlet for antidiabetic activity and mechanism in KKAy mice.

The mechanisms responsible for the antidiabetic activity of both the white ginseng radix (Ginseng Radix Alba, GRA) and the rootlet (Ginseng Radix Palva, GRP) were investigated. After a four week oral administration, the fasting blood glucose levels in the GRA- and GRP-treated groups were lower when compared to the control group. To elucidate the hypoglycemic mechanism(s) of the ginseng radices, glucose absorption from the small intestine, hepatic hexokinase and glucose-6-phosphatase activities, in addition to PPAR-gamma expression in adipose tissue were examined. The results strongly suggest that GRA can improve hyperglycemia in KKAy mice, possibly by blocking intestinal glucose absorption and inhibiting hepatic glucose-6-phosphatase, and GRP through the upregulation of adipocytic PPAR-y protein expression as well as inhibiting intestinal glucose absorption.

Animals↗
PubMed2001

Mechanisms of permeation and selectivity in calcium channels.

The mechanisms underlying ion transport and selectivity in calcium channels are examined using electrostatic calculations and Brownian dynamics simulations. We model the channel as a rigid structure with fixed charges in the walls, representing glutamate residues thought to be responsible for ion selectivity. Potential energy profiles obtained from multi-ion electrostatic calculations provide insights into ion permeation and many other observed features of L-type calcium channels. These qualitative explanations are confirmed by the results of Brownian dynamics simulations, which closely reproduce several experimental observations. These include the current-voltage curves, current-concentration relationship, block of monovalent currents by divalent ions, the anomalous mole fraction effect between sodium and calcium ions, attenuation of calcium current by external sodium ions, and the effects of mutating glutamate residues in the amino acid sequence.

Biophysical Phenomena↗
PubMed2001

Ellagic acid rhamnosides from the stem bark of Eucalyptus globulus.

Four ellagic acid rhamnosides were isolated from the stem bark of Eucalyptus globulus. Their structures have been established on the basis of the analysis of their 1H NMR, 13C NMR, HMBC, IR and MS spectral data. The HMBC data of these compounds were most useful for their structure determinations, with these bring determined to be 3-O-methylellagic acid 3'-O-alpha-rhamnopyranoside, 3-O-methylellagic acid 3'-O-alpha-3''-O-acetylrhamnopyranoside, 3-O-methylellagic acid 3'-O-alpha-2''-O-acetylrhamnopyranoside, 3-O-methylellagic acid 3'-O-alpha-4''-O-acetylrhamnopyranoside, respectively. Their antioxidant activities were evaluated by measuring the inhibition of lipid peroxidation using rat liver microsomes, with IC50 values of 10.0-14.0 microg/ml.

Animals↗
PubMed2001

Peritoneal dialysis in diabetic patients.

Diabetic nephropathy is the leading cause of end-stage renal disease worldwide. Although death rates of diabetic patients on hemodialysis and peritoneal dialysis (PD) have decreased substantially, they remain higher than rates in nondiabetics on both modalities. PD offers equal or better survival than hemodialysis for younger diabetic patients during early years of dialysis. PD technique survival does not appear different between diabetic and nondiabetic patients but is inferior to hemodialysis technique survival. PD may accelerate changes in peritoneal membrane structure and function in diabetics. Peritonitis and conventional PD solutions containing high glucose and glucose degradation products are implicated in PD technique failure. Increased peritoneal expression of vascular endothelial growth factor and transforming growth factor-beta1 and excessive accumulation of advanced glycosylation end products may be involved in the progressive increase in membrane permeability, loss of ultrafiltration, and peritoneal fibrosis. Nonglucose PD solutions or solutions containing low glucose degradation products may prevent or delay alterations in peritoneal membrane structure and function in diabetic as well as nondiabetic patients during long-term PD.

Diabetic Nephropathies↗
PubMed2001

Phenol block of peripheral nerve conduction: Titrating for optimum effect.

OBJECTIVES: To verify the dose-response relationship in phenol nerve block and to determine the concentration and volume of phenol injectate required for effective nerve conduction block. DESIGN: Before-after, experimental study. SETTING: A research institute laboratory. ANIMALS: Seventy-one New Zealand white rabbits. INTERVENTIONS: Group I (n = 48) received tibial nerve block by perineural injection (phenol, n = 40; saline, n = 8), group II (n = 21) by submerging the nerve in phenol solution. The 6 subgroups of group I each received different concentrations (3%, 4%, 5%) and volumes (0.1mL, 0.2mL, 0.3mL). The 2 subgroups of group II received 3% (n = 8) and 5% (n = 13) phenol. MAIN OUTCOME MEASURES: Compound muscle action potential (CMAP) and tension of triceps surae muscles by electric stimulation of the sciatic nerve were measured preintervention and at day 1, and weeks 1, 2, 4, and 8 postblock. Histologic studies were performed on 2 animals from group I. RESULTS: Two rabbits in group I died before results were obtained. In the remaining animals, CMAP amplitude reduced significantly (p <.05) as the volume of 5% phenol solution increased from 0.1mL, 0.2mL, to 0.3mL. A high concentration of phenol produced a more pronounced conduction block; however, no significant (p =.0589) difference existed among the 3 concentrations. Submerged tibial nerve had a greater degree of conduction block than perineurally injected nerve. Depth of the degeneration area in nerve fascicle varied with distance from the injection point. CONCLUSIONS: The nerve block effect of phenol can be titrated by adjusting the concentration and volume of phenol solution if the technique of application and localization of a block site are standardized.

Action Potentials↗
PubMed2001

Association between inflammation and changes in residual renal function and peritoneal transport rate during the first year of dialysis.

BACKGROUND: Peritoneal transport rate, a major determinant of peritoneal dialysis (PD) patient survival, increases in most patients starting on PD, while in other patients peritoneal transport rate may decline. Although several factors may contribute to changes in peritoneal transport rate, inflammation is known to be associated with a high peritoneal transport rate, and residual renal function (RRF), which often declines after start of PD, may also be related to inflammation. Therefore, we hypothesized that changes in peritoneal transport rate during patients' first year on PD and declining RRF may be linked with inflammation. METHODS: A total of 76 PD patients (40 males, mean age 56.8+/-14.1 years), who underwent two peritoneal equilibration tests at a mean of 0.4 months and 1 year after beginning PD, were included in the study. Based on the change in dialysate to plasma creatinine concentration ratio at 4-h dwell (D/P Cr) during first year on PD, the patients were divided into decreased or unchanged (group DUC; n=22) and increased (group I; n=54) groups. RESULTS: Initially, group I had a lower proportion of high transporters and more often high serum C-reactive protein (sCRP, > or =10 mg/l) and lower RRF compared with the DUC group. In group I, serum albumin and RRF decreased significantly and dialysate protein loss and glucose absorption increased significantly during the first year on PD. When patients were divided into two groups based on median change in RRF (1.9 ml/min), patients with a decrease in RRF >1.9 ml/min during first year on PD had a higher proportion of high sCRP, higher D/P Cr, and higher changes in D/P Cr compared to patients with a decrease in RRF < or =1.9 ml/min. Patients with elevated sCRP at one year included a higher proportion of patients who had high sCRP at the start of PD, higher increase in D/P Cr, lower serum albumin, lower RRF, and more decrease in RRF during first year on PD compared with patients having normal sCRP. RRF was inversely correlated with changes in D/P Cr during the first year on PD (r=-0.28, P=0.02). Multiple regression analysis revealed that the only factors affecting changes in D/P Cr were high sCRP and a low RRF. CONCLUSIONS: Our preliminary short-term study suggests that changes in peritoneal transport rate during patients' first year on PD may be linked with inflammation and declining residual renal function. Inflammation and residual renal function were identified as the only independent factors determining peritoneal transport rate during the first year on PD. It is possible that inflammation may cause both an increase in peritoneal transport rate and a decline in residual renal function, or that the decline in residual renal function and the increase in peritoneal transport rate may induce or aggravate inflammation. Further studies are needed to confirm these findings.

Adult↗
PubMed2001

The effect of prostaglandin E1 versus ischemia-reperfusion injury of musculocutaneous flaps.

The purpose of this study was twofold. To evaluate whether prostaglandin El can increase the survival of the flap, and to determine its function against ischemia-reperfusion injury in musculocutaneous flaps. Thirty-five Sprague-Dawley rats weighing 250 to 350 g were analyzed. The transverse rectus abdominis musculocutaneous flap was used in all rats. The rats were divided into three groups: group 1 (N = 15), the control group with 4-hour ischemic injury and intraflap injection of normal saline followed by reperfusion; group 2 (N = 15), prostaglandin E1 intraflap injection of 1 microg immediately after ischemic injury and reperfusion 4 hours later; and group 3 (N = 5), the sham-operated group. Analysis consisted of flap skin survival area measurements, immunohistochemical study using anti-intercellular adhesion molecule (anti-ICAM-1) monoclonal antibody, and histological evaluation including endothelium-sticking leukocytes at 24 hours and 5 days after reperfusion. The group treated with prostaglandin E1 showed immunohistochemical findings with decreased expression of ICAM-1 on the surface of the endothelium, and histology showed significant (p < 0.01) reduction of leukocyte adhesion at 24 hours and 5 days after reperfusion. These two factors were considered to play a role against ischemia-reperfusion injury, and led to improved survival of the flap. These results suggest that prostaglandin E1 may increase flap survival and may have a protective mechanism against ischemia-reperfusion injury by decreasing leukocyte-endothelial cell adhesion through decreased expression of ICAM-1.

Alprostadil↗
PubMed2000

A model of calcium channels.

We propose a model of calcium channels that can explain most of their observed properties, including the anomalous mole fraction effect and mutation of the glutamate residues. The structure grossly resembles that of the KcsA potassium channel except for the presence of an extracellular vestibule and a shorter selectivity filter containing four glutamate residues. Using this model in electrostatic calculations and Brownian dynamics simulations, we study mechanisms of ion permeation and selectivity in the channel. Potential energy profiles calculated for multiple ions in the channel provide explanations of ion permeation, the block of Na(+) currents by Ca(2+) ions, and many other observed properties. Brownian dynamics simulations provide quantitative predictions for the channel currents which reproduce available experimental data.

Calcium Channels↗
PubMed2000

Protein kinase C phosphorylation of syntaxin 4 in thrombin-activated human platelets.

We postulated that the syntaxins, because of their key role in SNARE complex formation and exocytosis, could be important targets for signaling by intracellular kinases involved in secretion. We found that syntaxin 4 was phosphorylated in human platelets treated with a physiologic agent that induces secretion (thrombin) but not when they were treated with an agent that prevents secretion (prostacyclin). Syntaxin 4 phosphorylation was blocked by inhibitors of activated protein kinase C (PKC), and, in parallel assays, PKC inhibitors also blocked secretion from thrombin-activated platelets. In platelets, cellular activation by thrombin or phorbol 12-myristate 13-acetate decreased the binding of syntaxin 4 with SNAP-23, another platelet t-SNARE. Phosphatase inhibitors increased syntaxin 4 phosphorylation and further decreased syntaxin 4-SNAP-23 binding induced by cell activation. Conversely, a PKC inhibitor blocked syntaxin 4 phosphorylation and returned binding of syntaxin 4-SNAP-23 to that seen in nonstimulated platelets. In vitro, PKC directly phosphorylated platelet syntaxin 4 and recombinant syntaxin 4. PKC phosphorylation in vitro inhibited (71 +/- 8%) the binding of syntaxin 4 to SNAP-23. These results provide evidence that extracellular activation can be coupled through intracellular PKC signaling so as to modulate SNARE protein interactions involved in platelet exocytosis.

Blood Platelets↗
PubMed2000

Molecular dynamics estimates of ion diffusion in model hydrophobic and KcsA potassium channels.

Molecular dynamics simulations are carried out to obtain estimates of diffusion coefficients of biologically important Na+, K+, Ca2+ and Cl- ions in hydrophobic cylindrical channels with varying radii and large reservoirs. Calculations for the cylindrical channels are compared to those for the KcsA potassium channel, for which the protein structure has recently been determined from X-ray diffraction experiments. Our results show that ion diffusion is maintained at reasonably high levels even within narrow channels, and does not support the very small diffusion coefficients used in some continuum models in order to fit experimental data. The present estimates of ion diffusion coefficients are useful in the calculation of channel conductance using the Poisson-Nernst-Planck theory, or Brownian dynamics.

Algorithms↗
PubMed2000

Pharmacological characterization of (10bS)-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinoline oxalate (YSL-3S) as a new alpha2-adrenoceptor antagonist.

Alpha2-adrenoceptor antagonists, which can enhance synaptic norepinephrine levels by blocking feedback inhibition processes, are potentially useful in the treatment of disease states such as depression, memory impairment, impotence and sexual dysfunction. (10bS)-1,2,3,5,6,10b-Hexahydropyrrolo[2,1-a]isoquinoline oxalate (YSL-3S) was evaluated in several in vitro biological tests to establish its pharmacological profile of activities as an alpha2-adrenoceptor antagonist. Saturation binding assay revealed that [3H]rauwolscine bound to the alpha2-adrenoceptors with a Kd value of 6.3+/-0.5 nM and a Bmax value of 251+/-39 fmol/mg protein in rat cortical synaptic membranes. Competitive binding assay showed that YSL-3S inhibited the binding of [3H]rauwolscine (1 nM) in a concentration-dependent manner with a Ki value of 98.2+/-12.1 nM while it did not inhibit the binding of [3H]cytisine (1.25 nM) to neuronal nicotinic cholinergic receptors. The Ki values of yohimbine, clonidine and norepinephrine for [3H]rauwolscine binding were 15.8+/-1.0, 40.1+/-5.9 and 40.0+/-11.5 nM, respectively. In addition, the binding affinity of YSL-3S for alpha2-adrenoceptors was higher than that of its antipode and the racemic mixture. The functional activity of YSL-3S at the presynaptic alpha2-adrenoceptors was assessed using the prostatic portion of the rat vas deferens. Clonidine inhibited field-stimulated contractions of the vas deference in a dose-dependent manner. The presence of YSL-3S or yohimbine caused a parallel, rightward the dose-response curve of clonidine in a dose-dependent manner, indicating an antagonistic action at the presynaptic alpha2-adrenoceptors. The pA2 values of yohimbine and YSL-3S were 7.66+/-0.13 and 6.64+/-0.18, respectively. The results indicate that YSL-3S acts as a competitive antagonist at presynaptic alpha2-adrenoceptors with a potency approximately ten times lower than yohimbine, but is devoid of binding affinity for neuronal nicotinic cholinergic receptors.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed2000

Lipid peroxidation inhibitory activity of some constituents isolated from the stem bark of Eucalyptus globulus.

Twelve compounds with lipid peroxidation inhibitory activity were isolated from the stem bark of E. globulus. Their structures were assigned as a new aromatic monoterpene (1) and eleven known compounds, pinoresinol (2), vomifoliol (3), 3,4,5-trimethoxyphenol 1-O-beta-D-(6'-O-galloyl)glucopyranoside (4), methyl gallate (5), rhamnazin (6), rhamnetin (7), eriodictyol (8), quercetin (9), taxifolin (10), engelitin (11), and catechin (12) on the basis of UV, mass, and NMR spectroscopic analyses. These compounds except vomifoliol significantly inhibited lipid peroxidation in rat liver microsome.

Animals↗
PubMed2000

Tests of continuum theories as models of ion channels. I. Poisson-Boltzmann theory versus Brownian dynamics.

Continuum theories of electrolytes are widely used to describe physical processes in various biological systems. Although these are well-established theories in macroscopic situations, it is not clear from the outset that they should work in small systems whose dimensions are comparable to or smaller than the Debye length. Here, we test the validity of the mean-field approximation in Poisson-Boltzmann theory by comparing its predictions with those of Brownian dynamics simulations. For this purpose we use spherical and cylindrical boundaries and a catenary shape similar to that of the acetylcholine receptor channel. The interior region filled with electrolyte is assumed to have a high dielectric constant, and the exterior region representing protein a low one. Comparisons of the force on a test ion obtained with the two methods show that the shielding effect due to counterions is overestimated in Poisson-Boltzmann theory when the ion is within a Debye length of the boundary. As the ion gets closer to the boundary, the discrepancy in force grows rapidly. The implication for membrane channels, whose radii are typically smaller than the Debye length, is that Poisson-Boltzmann theory cannot be used to obtain reliable estimates of the electrostatic potential energy and force on an ion in the channel environment.

Algorithms↗
PubMed2000

Tests of continuum theories as models of ion channels. II. Poisson-Nernst-Planck theory versus brownian dynamics.

We test the validity of the mean-field approximation in Poisson-Nernst-Planck theory by contrasting its predictions with those of Brownian dynamics simulations in schematic cylindrical channels and in a realistic potassium channel. Equivalence of the two theories in bulk situations is demonstrated in a control study. In simple cylindrical channels, considerable differences are found between the two theories with regard to the concentration profiles in the channel and its conductance properties. These differences are at a maximum in narrow channels with a radius smaller than the Debye length and diminish with increasing radius. Convergence occurs when the channel radius is over 2 Debye lengths. These tests unequivocally demonstrate that the mean-field approximation in the Poisson-Nernst-Planck theory breaks down in narrow ion channels that have radii smaller than the Debye length.

Algorithms↗
PubMed2000

Biocompatibility of new peritoneal dialysis solutions: what can we hope to achieve?

Despite the bioincompatibility of the "old", standard, high glucose, lactate-buffered peritoneal dialysis (PD) solutions, PD is itself a highly successful dialysis modality with patient survival equivalent to that of hemodialysis (HD) during the initial 3 - 5 years of dialysis therapy. Nevertheless, PD technique survival is often limited by infectious complications and alterations in the structure and function of the peritoneal membrane. These local changes also have a negative impact on patient survival owing to systemic effects such as those often seen in patients with high peritoneal transport rate and loss of ultrafiltration (UF) capacity. Patient mortality remains unacceptably high in both HD and PD patients, with most premature deaths being associated with signs of malnutrition, inflammation, and atherosclerotic cardiovascular disease (MIA syndrome). These systemic signs are likely to be influenced by PD solutions both directly and indirectly (via changes in the peritoneal membrane). New, biocompatible PD solutions may have favorable local effects (viability and function of the peritoneal membrane) and systemic effects (for example, on MIA syndrome). Amino acid-based solution [Nutrineal (N): Baxter Healthcare Corporation, Deerfield, IL, U.S.A.] may improve nutritional status as well as peritoneal membrane viability. Bicarbonate/lactate-buffered solution [Physioneal (P): Baxter Healthcare Corporation] may ameliorate local and systemic effects of low pH, high lactate, and high glucose degradation products. Icodextrin-based solution [Extraneal (E): Baxter Healthcare SA, Castlebar, Ireland] may improve hypertension and cardiovascular problems associated with fluid overload and may extend time on therapy in patients with loss of UF capacity. The positive effects of each of these new, biocompatible solutions have been demonstrated in several studies. It is likely that the combined use of N, P, and E solutions will produce favorable synergies in regard to both local effects (peritoneal viability) and systemic effects (less malnutrition, inflammation, and fluid overload). Solution combination is an exciting area for clinical study in the coming years. Furthermore, dialysis fluid additives such as hyaluronan, which protects and improves the function of the peritoneal membrane, may further improve PD solutions. The new, biocompatible PD solutions represent an entirely new era in the evolution of the PD therapy; they are likely to have markedly positive effects on both PD technique and PD patient survival in coming years.

Amino Acids↗