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H Sun

Publications and source records attributed to H Sun.

At least 73 records · Page 4Linked to original sources
PubMed2001

Nerve injury-induced tactile allodynia is mediated via ascending spinal dorsal column projections.

Peripheral nerve injury produces signs of neuropathic pain including tactile allodynia and thermal hyperalgesia, sensory modalities which may be associated with different neuronal pathways. Studies of spinally-transected, nerve-injured rats have led to suggestions that thermal hyperalgesia may be mediated predominately through local spinal circuitry whereas ascending input to supraspinal sites is critical to the manifestation of tactile allodynia. Here, the nature of ascending spinal input mediating tactile allodynia was explored using selective spinal lesions. Male Sprague-Dawley rats received L(5)/L(6) spinal nerve ligation (SNL) and ipsilateral or contralateral (relative to the SNL side) lesions including spinal hemisections and bilateral and unilateral dorsal column lesions. The rats were maintained in a sling and monitored for tactile allodynia by measuring withdrawal thresholds to probing with von Frey filaments 24 h after the hemisection. Rats receiving dorsal column lesions demonstrated no motor deficits while rats receiving spinal hemisection showed paralysis of the paw which nevertheless responded to strong noxious stimulation. Spinal hemisection ipsilateral, but not contralateral, to SNL completely abolished tactile allodynia while maintaining spinal nocifensive reflexes to noxious pinch. Bilateral and ipsilateral dorsal column lesions blocked tactile allodynia while contralateral dorsal column lesions did not. Administration of lidocaine into the nucleus gracilis ipsilateral to SNL also blocked tactile allodynia, but did not alter thermal hyperalgesia in SNL rats or increase thermal nociceptive responses in sham-operated rats. Lidocaine microinjected into the contralateral nucleus gracilis produced no changes in responses to tactile or thermal stimuli in either group. These results indicate that tactile allodynia after peripheral nerve injury is dependent upon inputs to supraspinal sites. Furthermore, it is apparent that afferent signals interpreted as tactile allodynia course through the ipsilateral dorsal columns and are relayed through the nucleus gracilis. This neuronal pathway is consistent with the interpretation that tactile allodynia pursuant to peripheral nerve injury is transmitted to the central nervous system by means of large diameter, myelinated fibers.

Anesthetics, Local↗
PubMed2001

ABCR, the ATP-binding cassette transporter responsible for Stargardt macular dystrophy, is an efficient target of all-trans-retinal-mediated photooxidative damage in vitro. Implications for retinal disease.

A large body of experimental and clinical data have documented the damaging effects of light exposure on photoreceptor cells although the identities of the biologically relevant molecular targets of photodamage are still uncertain. Several lines of evidence point to retinoids or retinoid derivatives as chromophores that can mediate light damage. We report here that ABCR, a photoreceptor-specific transporter involved in the recycling of all-trans-retinal, is unusually sensitive to photooxidation damage mediated by all-trans-retinal in vitro. Partial loss of ABCR function is responsible for Stargardt macular dystrophy, which is associated with accumulation of A2E, a diretinoid adduct within the retinal pigment epithelium. Photodamage to ABCR causes it to aggregate in SDS gels and results in the loss of retinal-stimulated ATPase activity. Peripherin/RDS and ROM-1, two structural proteins that colocalize with ABCR at the outer segment disc rim, are also significantly more susceptible to all-trans-retinal-mediated photodamage than are the major proteins from the rod outer segment. These observations imply that there may be specific protein targets of photodamage within the outer segment, and they may be especially relevant to assessing the risk of light exposure in those individuals who already have diminished ABCR activity due to mutation in one or both copies of the ABCR gene.

ATP-Binding Cassette Transporters↗
PubMed2001

Selective degradation of oxidized calmodulin by the 20 S proteasome.

We have investigated the mechanisms that target oxidized calmodulin for degradation by the proteasome. After methionine oxidation within calmodulin, rates of degradation by the 20 S proteasome are substantially enhanced. Mass spectrometry was used to identify the time course of the proteolytic fragments released from the proteasome. Oxidized calmodulin is initially degraded into large proteolytic fragments that are released from the proteasome and subsequently degraded into small peptides that vary in size from 6 to 12 amino acids. To investigate the molecular determinants that result in the selective degradation of oxidized calmodulin, we used circular dichroism and fluorescence spectroscopy to assess oxidant-induced structural changes. There is a linear correlation between decreases in secondary structure and the rate of degradation. Calcium binding or the repair of oxidized calmodulin by methionine sulfoxide reductase induces comparable changes in alpha-helical content and rates of degradation. In contrast, alterations in the surface hydrophobicity of oxidized calmodulin do not alter the rate of degradation by the proteasome, indicating that changes in surface hydrophobicity do not necessarily lead to enhanced proteolytic susceptibility. These results suggest that decreases in secondary structure expose proteolytically sensitive sites in oxidized calmodulin that are cleaved by the proteasome in a nonprocessive manner.

Adenosine Triphosphatases↗
PubMed2001

Use of lipid-lowering medications at discharge in patients with acute myocardial infarction: data from the National Registry of Myocardial Infarction 3.

BACKGROUND: The present study aimed to assess use of lipid-lowering medication at discharge in a current national sample of patients hospitalized with acute myocardial infarction and to evaluate factors associated with prescribing patterns. METHODS AND RESULTS: Demographic, procedural, and discharge medication data were collected from 138 001 patients with acute myocardial infarction discharged from 1470 US hospitals participating in the National Registry of Myocardial Infarction 3 from July 1998 to June 1999. Lipid-lowering medications were part of the discharge regimen in 31. 7%. Among patients with prior history of CAD, revascularization, or diabetes, less than one half of the patients were discharged on treatment. In multivariate analysis, factors independently related to lipid-lowering use included history of hypercholesterolemia (odds ratio [OR] 4.93; 95% CI 4.79 to 5.07), cardiac catheterization during hospitalization (OR 1.29; 95% CI 1.24 to 1.34), care provided at a teaching hospital, (OR 1.26; 95% CI 1.22 to 1.32), use of ss-blocker (OR 1.43; 95% CI 1.39 to 1.48), and smoking cessation counseling (OR 1.51; 95% CI 1.44 to 1.59). Lipid-lowering medications were given less often to patients who were older (65 to 74 versus <55 years of age; OR 0.82; 95% CI 0.78 to 0.86), those with a history of hypertension (OR 0.92; 95% CI 0.89 to 0.95), and those undergoing coronary artery bypass graft surgery (OR 0.58; 95% CI 0.55 to 0.60). CONCLUSIONS: Analysis of current practice patterns for the use of lipid-lowering medications in patients hospitalized with acute myocardial infarction reveals that a significant proportion of high-risk patients did not receive treatment at time of discharge.

Aged↗
PubMed2001

Variations of dose and electrode spacing for rat breast cancer electrochemical treatment.

Electrochemical treatment (EChT) with direct current delivered through implanted electrodes has been used for local control of solid tumors in humans. This study tested the hypothesis that rat breast cancer responses to EChT are dependent on electrode spacing and dose, and explored suitable parameters for treating breast cancers with EChT. Rat breast cancers were initiated by injecting 1 x 10(6) MTF-7 cells to the right mammary gland fat pad of Fisher 344 female rats. The rats were randomly divided into designated experimental groups when the tumors grew to approximately 2 x 2 x 2 cm. One hundred and thirty rats were used for a survival study and 129 for a pathology study. A 4-channel EChT machine was used to administer coulometric doses. The survival study indicated that local tumor control rate is less than 40% in the 40 coulomb (C) and 60 C groups and more than 70% in the 80 and 100 C groups. Sixty six rats died of primary tumors, including all 10 rats in the control group. Once a rat's primary tumor was controlled, no recurrence was found. The main reason for terminating the primary tumor-free rats (51) was lymph node metastasis. Thirteen tumor-free rats survived for more than 6 months. The pathology study showed a significant dose effect on EChT induced tumor necrosis. At 10, 20, 40, and 80 C, the fraction showing necrosis were 39.7, 52.3, 62, and 77.7%, respectively (P </= 0.001). Electrodes spacing was not an important factor within a given range. At 5, 10, and 15 mm spacing, the fraction showing the necrosis were 54.1, 60.4, and 59.2%, respectively (P = 0.552). The overlap rate of necroses was similar in the 5 and 10 mm groups (82.5 and 85%) and lower in the 15 mm group (65%). We conclude that the tumor responses to EChT, local control, survival rates, and necrosis percentages were significantly increased with increasing dose. The changes in electrode spacing (3, 5, and 10 mm) did not significantly affect the tumor responses to EChT within the same dose. For a diameter of 2.0-2.5 cm rat breast cancer, EChT should be applied with 5-10 mm spacing and a minimum dosage of 80 C.

Animals↗
PubMed2001

Effect of ligustrazine on hematopoiesis in bone marrow transplantation mice.

The effect of Ligustrazine on the hematopoiesis after bone marrow transplantation (BMT) in allogenic BMT mice was investigated. After the typical mice model of allogenic BMT had been established, the mice were randomly divided into three groups: BMT group, Ligustrazine group and normal group. The BMT group was given normal saline (0.2 ml, twice a day) through gastric tube, while the Ligustrazine group was given Ligustrazine through gastric tube (0.2 ml, twice a day). At the 1st, 7th and 14th day after BMT, we observed the peripheral blood cells and bone marrow nuclear cells (BMNC), as well as the expression level of Heparan Sulfate (HS) and stromal cell derived factor-1 (SDF-1) on bone marrow sections by using immunohistochemistry (SABC-AP), the expression of CXCR4 on the BMNC. The results showed that on the 7th and 14th day, the peripheral blood white cells, platelets, BMNC and the expression levels of CXCR4, HS and SDF-1 were significantly higher in Ligustrazine group than in the BMT group (P < 0.05). It was concluded that Ligustrazine could promote hematopoiesis at the early stage of hematopoietic reconstitution after BMT.

Animals↗
PubMed2001

Selective spinal anesthesia for outpatient laparoscopy. IV: population pharmacodynamic modelling.

PURPOSE: To apply a population pharmacodynamic model to small-dose hypobaric spinal anesthesia for outpatient laparoscopy. METHODS: The level of spinal analgesia after spinal blockade with small-dose (20-25 mg) hypobaric lidocaine was assessed by means of pinprick in patients undergoing outpatient laparoscopy. In 57 patients, 385 measurements were available for analysis. We first modelled the data for each patient with a mixed-effects model described by Schnider (Model 1). The population mean parameters, inter-individual variance, and residual variance were estimated. Clinically important endpoints (time to reach T10 (onset), time to maximal level, duration and maximally attained level) of each patient were calculated based on the estimated time course of analgesia level for each patient. The model was used to predict the later data with respect to level of spinal analgesia of each patient from fits based on the observed data in the first 75 min. RESULTS: The mean +/- SD onset time was 8.3 +/- 1.9 min, time to maximal level was 20.8 +/- 5.3 min, duration of effect was 37.9 +/- 13.1 min, and mean maximal level was T5. There was a good correlation (R2 = 0.90) between the observed levels of analgesia and those predicted from the model. Data from the first 75 min predicted the later observed data for each patient moderately well (R2 = 0.38). CONCLUSION: A population pharmacodynamic model was applied to low-dose hypobaric lidocaine spinal anesthesia. Clinically important endpoints were determined and forecasting of later data with respect to level of spinal analgesia was attempted. Such an approach may be useful in the management of low-dose spinal anesthetic techniques in outpatients.

Adult↗
PubMed2001

Derivative hydride generation atomic absorption spectrometry and determination of lead traces in waters.

Fundamentals of derivative hydride-generation atomic absorption spectrometry (DHGAAS) are described. A linear relationship was obtained between the derivative absorbance and the concentration of analysis in a sample. The new DHGAAS method was applied to the determination of traces of lead in water. The conditions affecting the derivative absorbance of lead were evaluated and optimized. The detection limit and sensitivity of the proposed method were 26 times and 8.8 times better, respectively, than those of conventional hydride-genera-tion atomic absorption spectrometry. The characteristic concentration (for a derivative absorbance of 0.0044) and detection limit (3sigma) for lead were 0.017 and 0.096 ng mL(-1), respectively, for a 2 mV min(-1) sensitivity range setting. The recovery range was 92.5-103%.

Acids↗
PubMed2001

Intracellular calcium changes and tachycardia-induced contractile dysfunction in canine atrial myocytes.

OBJECTIVES: Indirect evidence suggests a role for Ca(2+)-overload in electrical and mechanical alterations caused by atrial tachycardia. The present study assessed the alterations in cellular [Ca(2+)] and contractile function caused by rapid atrial cellular activation. METHODS: Intracellular Ca(2+) transients (CaT) and cell shortening (CS) were measured by microfluorometry (Indo-1 AM) and video edge-detection in isolated, field-stimulated canine atrial myocytes (37 degrees C). RESULTS: Abrupt increases in frequency (0.3-3 Hz) caused rapid increases in diastolic [Ca(2+)]i (DCa) that were maintained during rapid-pacing for up to 50 min. When short-term (3-min) rapid-pacing was imposed, CaT and CS increased initially upon returning to 0.3 Hz, but then declined rapidly to 64+/-5 and 49+/-7%, respectively, of pre-tachycardia values, returning to control after approximately 15 min. Post-tachycardia CaT and CS reductions were prevented by decreasing [Ca(2+)]o during tachycardia to prevent Ca(2+)-overload. CS reductions correlated with indices of Ca(2+) loading during tachycardia. Restoration of CaT to normal during post-tachycardia contractile dysfunction (by increasing [Ca(2+)]o) returned CS to normal, indicating that reduced Ca(2+) release, not reduced myofilament Ca(2+)-sensitivity, caused post-tachycardia contractile failure. Estimation of sarcoplasmic-reticulum Ca(2+)-stores (caffeine-induced Ca(2+)-release) confirmed tachycardia-induced Ca(2+)-loading and suggested that reduced Ca(2+)-stores decreased Ca(2+)-release post-tachycardia. CONCLUSIONS: Atrial tachycardia increases cellular Ca(2+)-loading, leading to post-tachycardia abnormalities in Ca(2+)-handling that produce contractile dysfunction. These findings are the first direct evidence for the frequently-postulated role of Ca(2+)-overload in tachycardia-induced abnormalities of atrial function.

Animals↗
PubMed2001

Taxane diterpenoids from the bark of Taxus yunnanensis.

Further investigation on the alcohol extract of the barks of Taxus yunnanensis led to the isolation of four taxoids, namely, 7beta-xylosyl-taxol D, taxuyunnanines P, Q and R, along with the known taxuyuntin G (2). Four are rearranged taxoids with an 11(15-->1)-abeotaxoid skeleton and an opened oxetane ring moiety. Structures were determined by spectroscopic and chemical means.

Diterpenes↗
PubMed2001

Hemodynamic determinants of the mitral annulus diastolic velocities by tissue Doppler.

OBJECTIVES: Our goal was to identify the hemodynamic determinants of the mitral annulus (MA) diastolic velocities by tissue Doppler. BACKGROUND: The MA diastolic velocities are promising indexes of left ventricular (LV) diastolic function. However, their hemodynamic determinants have not yet been evaluated. METHODS: Ten adult mongrel dogs underwent left atrial (LA) and LV pressure measurements by Millar catheters while tissue Doppler was applied to record the MA diastolic velocities at the septal and lateral comers. Conventional transmitral flow was also obtained. Left atrial and LV pressures were modified utilizing fluid administration and caval occlusion, whereas dobutamine and esmolol were used to change LV and LA relaxation. Left ventricular filling pressures were altered during different lusitropic states to evaluate for the possible interaction of preload and LV relaxation on the early diastolic velocity (Ea). RESULTS: In the majority of dogs, a positive significant relation was observed between Ea and the transmitral pressure gradient (r = 0.57, p = 0.04). The Ea had strong correlations with tau (r = -0.83, p < 0.001), LV -dP/dt (r = 0.8, p < 0.001) and minimal LV pressure (r = -0.76, p < 0.01). However, there was no relation between Ea and the transmitral pressure gradient in experimental stages where tau >50 ms. Furthermore, the late diastolic velocity at both corners of the MA had significant positive relations with LA dP/dt (r = 0.67, p < 0.01) and LA relaxation (r = 0.73, p < 0.01) but an inverse correlation with LV end-diastolic pressure (r = -0.53, p = 0.01). CONCLUSIONS: Left ventricular relaxation, minimal pressure and preload determine Ea while late diastolic velocity determinants include LA dP/dt, LA relaxation and LV end-diastolic pressure.

Animals↗
PubMed2001

Benzophenones and xanthones with isoprenoid groups from Cudrania cochinchinensis.

Four new benzophenones with two isoprenoid groups, cudraphenones A-D (1-4), and three new xanthones also with two isoprenoid units, cudraxanthones P-R (5-7), were isolated from the roots of Cudraniacochinchinensis, together with 19 known phenolic compounds. The structures of the new compounds were elucidated by spectroscopic methods. Some compounds exhibited weak cytotoxicity against human oral squamous carcinoma cells (HSC-2) and normal human gingival fibroblasts (HGF). Among them, benzophenones 1-4 showed more potent cytotoxic activities against HSC-2 cells than against HGF cells. On the other hand, xanthones bearing isoprenoid groups showed much lower tumor specificity as compared with the benzophenones, except for geronthxanthone H and isoalvaxanthone. The presence of two sets of hydrophobic and hydrophilic groups in separate domains in each molecule might play a role in the mediation of tumor-specific action.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Mechanistic studies of ABCR, the ABC transporter in photoreceptor outer segments responsible for autosomal recessive Stargardt disease.

ABCR is an ABC transporter that is found exclusively in vertebrate photoreceptor outer segments. Mutations in the human ABCR gene are responsible for autosomal recessive Stargardt disease, the most common cause of early onset macular degeneration. In this paper we review our recent work with purified and reconstituted ABCR derived from bovine retina and from cultured cells expressing wild type or site-directed mutants of human ABCR. These experiments implicate all-trans-retinal (or Schiff base adducts between all-trans-retinal and phosphatidylethanolamine) as the transport substrate, and they reveal asymmetric roles for the two nucleotide binding domains in the transport reaction. A model for the retinal transport reaction is presented which accounts for these experimental observations.

ATP-Binding Cassette Transporters↗
PubMed2001

Effect of probenecid on fluorescein transport in the central nervous system using in vitro and in vivo models.

PURPOSE: The purpose of this study was to characterize the function of multidrug resistance-associated proteins (MRPs) (or MRP-like organic anion transport systems) in the blood-brain harrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) using both an in vitro BBB model and an in vivo microdialysis model. METHODS: In vitro functional studies were performed using bovine brain microvessel endothelial cells (BBMEC). The accumulation of fluorescein, an anionic fluorescent dye, in BBMEC was determined with and without the presence of inhibitors of various efflux transport proteins. In vivo microdialysis simultaneously monitored fluorescein concentrations in cortical extracellular fluid and cerebrospinal fluid. The effect of probenecid on the in vivo distribution of fluorescein was studied using a balanced crossover design in the rat. RESULTS: In vitro experiments showed that probenecid, indomethacin, LY-329146, and all MRP inhibitors significantly increased (two- to threefold) the accumulation of fluorescein in BBMEC, whereas LY-335979, a P-gp inhibitor, had no effect on the accumulation of fluorescein. Probenecid significantly increased fluorescein plasma concentration and the plasma free fraction in vivo. The distribution of fluorescein across the BBB and BCSFB was enhanced by 2.2- and 1.9-fold, respectively, when probenecid was coadministered, even after correction for increased fluorescein plasma concentrations and free fraction. CONCLUSIONS: These results demonstrate that MRPs or MRP-like transport system(s) may play an important role in fluorescein distribution across both BBB and BCSFB. This study showed that microdialysis proved to be a powerful in vivo technique for the study of transport systems in the central nervous system, and in vitro/in vivo correlations are possible using these model systems.

Algorithms↗
PubMed2001

Defective T cell activation and autoimmune disorder in Stra13-deficient mice.

Stra13, a basic helix-loop-helix transcription factor, is up-regulated upon activation of CD4+ T cells. Here we show that Stra13-deficient mice exhibit defects in several phases of CD4+ T cell activation. In vivo, Stra13 deficiency results in ineffective elimination of activated T and B cells, which accumulate progressively, leading to lymphoid organ hyperplasia. Consequently, aging Stra13-/- mice develop autoimmune disease characterized by accumulation of spontaneously activated T and B cells, circulating autoantibodies, infiltration of T and B lymphocytes in several organs and immune complex deposition in glomeruli. Our studies identify Stra13 as a key regulator of lymphocyte activation that is vital for maintenance of self-tolerance and for constraint of autoimmunity.

Aging↗
PubMed2001

Electrical conduits within the inferior atrial region exhibit preferential roles in interatrial activation.

Differences between conduction properties of interatrial conduits and their roles in initiation and maintenance of supraventricular arrhythmias remain unclear. Our objective was to determine details of interatrial activation in inferior atrial region and to correlate intra-atrial and interatrial activation patterns with the site of origin of atrial ectopic activation. In 9 dogs, basket-catheters carrying 64 electrodes were deployed into both the right atrium (RA) and left atrium (LA). A 10-electrode catheter was inserted into the coronary sinus (CS). Activation patterns of the RA, LA, and CS were compared during pacing in the CS, in RA inferoparaseptum posterior to Eustachian ridge-tendon of Todaro (TT), and in inferior RA near the CS ostium (anterior to TT). We found that pacing in proximal and middle CS resulted in a RA breakthrough invariably at the CS ostium, consistent with conduction through a CS-RA connection. Meanwhile, LA breakthrough emerged in inferoposterior region (inferior to mitral annulus), suggesting conduction through a CS-LA connection. While pacing in distal CS, LA breakthrough shifted to middle posterolateral wall. Whereas, the RA was activated by the LA directly through the septum. During pacing in RA inferoparaseptum posterior to TT, the LA was activated directly through the septum at 22 +/- 4 ms. Whereas, during pacing anterior to TT, the LA was activated through both the CS and the septum while earliest activation was delayed by 38 +/- 5 ms. In conclusion, both the interatrial septum and CS musculature form electrical conduits in inferior atrial region in canine. Differences in activation properties between the conduits in inferior interatrial region result in selective interatrial activation patterns during ectopic activation.

Animals↗