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Biomedical subjects

M S Wang

Publications and source records attributed to M S Wang.

At least 37 records · Page 2Linked to original sources

Oral administration of a nonimmunosuppressant FKBP-12 ligand speeds nerve regeneration.

We recently showed that s.c. injections of a nonimmunosuppressant FK506 binding protein-12 (FKBP-12) ligand (V-10,367) accelerates nerve regeneration in the rat sciatic nerve crush model. Here we examined the oral efficacy of this compound for speeding nerve regeneration. Rats receiving V-10,367 (5, 15 or 50 mg/kg/day) by oral gavage all demonstrated an increase in nerve regeneration compared to vehicle-treated controls. Functional recovery was observed earliest and axonal calibers of regenerating axons in the soleus nerve were largest in the 15 mg/kg group, mean axonal areas being increased by 66% compared to controls. Orally active nonimmunosuppressant FKBP-12 ligands may be useful for the treatment of human peripheral nerve disorders.

Administration, Oral↗

Semidry electroblotting of peptides and proteins from acid-urea polyacrylamide gels.

A semidry electrophoretic transfer method was developed for efficient electroblotting of proteins separated by acid-urea polyacrylamide gel electrophoresis (AU-PAGE). Model polypeptides ranging from 1.8 to 21.5 kDa were used to test transfer parameters that included time of transfer, power settings, transfer solutions, and membrane type. Optimized conditions were identified which allowed for transfer efficiencies of 70-100% following 5-15 min of applied current. The best transfer solution was 5% acetic acid, the same solvent used for electrophoresis. Therefore, acid-urea gels could be subjected to electrophoretic transfer without a soaking step, thereby reducing loss of band resolution and eliminating leaching of protein from the gel. The method was shown to be applicable to Western blot analysis of rat neutrophil defensins.

Acetic Acid↗

A nonimmunosuppressant FKBP-12 ligand increases nerve regeneration.

The immunosuppressant drugs FK506 and cyclosporin A inhibit T-cell proliferation via a common mechanism: calcineurin inhibition following binding to their respective binding proteins, the peptidyl prolyl isomerases FKBP-12 and cyclophilin A. In contrast, FK506, but not cyclosporin A, accelerates nerve regeneration. In the present study, we show that the potent FKBP-12 inhibitor V-10,367, which lacks the structural components of FK506 required for calcineurin inhibition, increases neurite outgrowth in SH-SY5Y neuroblastoma cells and speeds nerve regeneration in the rat sciatic nerve crush model. In SH-SY5Y cells, V-10,367 increased the lengths of neurite processes in a concentration-dependent (between 1 and 10 nM) fashion over time (up to 168 h). Daily subcutaneous injections of V-10,367 accelerated the onset of clinical signs of functional recovery in the hind feet compared to vehicle-treated control animals. Interdigit distances (between the first and fifth digits) measured on foot prints obtained during walking showed an increase in toe spread in V-10,367-treated rats compared to vehicle-treated controls. Electron microscopy demonstrated larger regenerating axons distal to the crush site in the sciatic nerve from V-10,367-treated rats. Quantitation of axonal areas in the soleus nerve revealed a shift to larger axonal calibers in V-10,367-treated rats (400 or 200 mg/kg/day); mean axonal areas were increased by 52 and 59%, respectively, compared to vehicle-treated controls. FKBP-12 ligands lacking calcineurin inhibitory activity represent a new class of potential drugs for the treatment of human peripheral nerve disorders.

Animals↗

Facilitation of retinal function recovery by coumarin derivatives.

Ischemic retinopathy is a difficult disease to treat, although numerous drugs have been tried in the clinics. Coumarin was one of those tried as an anti-coagulant with a marginal efficacy. In this study, 15 coumarin derivatives were studied on the b-wave recovery in electroretinogram which is an indicator of the functional recovery of retina after ischemic insult. It was found that when positions 6, 7 and 8 were occupied by various functional groups, the b-wave recovery could be markedly enhanced. On the other hand, single occupation of position 3 with any functional group would cause damaging effects to the anti-ischemic activity. It is concluded that some coumarin derivatives with two or all of these positions at 6, 7 and 8 occupied by certain functional groups could result in useful drugs for the treatment of ischemic retinopathy.

Animals↗

Inhibition of 11 beta-hydroxysteroid dehydrogenase obtained from guinea pig kidney by some bioflavonoids and triterpenoids.

AIM: To study the inhibitory effect of some bioflavonoids and triterpenoids on 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) from guinea pig kidney. METHOD: The 11 beta-OHSD of kidney cortex microsomes in addition of cortisol was incubated in the presence of NADP, Triton DF-18, and the test compounds at 37 degrees C for 1 h. The enzyme activity was assayed by measuring the rate of conversion of cortisol to cortisone eluted with HPLC gradient analysis. RESULTS: The IC50 (95% confidence limits) values of glycyrrhizic acid, naringenin, fisetin, emodin were 254 (202-320), 336 (270-418), 470 (392-564), and 527 (425-653) mumol.L-1, respectively. The inhibitory effect of oleanolic acid was 2-fold stronger than that of astramembranin I. The mode of action of naringenin was competitive inhibition. CONCLUSION: The test compounds inhibited the 11 beta-OHSD in kidney cortex with different potencies as glycyrrhizic acid did.

11-beta-Hydroxysteroid Dehydrogenases↗

NAD- and NADP-dependent 11 beta-hydroxysteroid dehydrogenase isoforms in guinea pig kidney with gossypol inhibition.

AIM: To study the mechanism of gossypol-induced hypokalemia. METHODS: The 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) protein was prepared from guinea pig kidney. The activity of 11 beta-OHSD with NAD or NADP as the coenzyme was measured by HPLC in both control and gossypol treatment. RESULTS: The Vmax and K(m) were 0.64 mmol.h-1/g protein and 0.07 mumol (cortisol) for NAD-dependent 11 beta-OHSD, 1.75 mmol.h-1/g protein and 0.21 mumol (cortisol) for NADP-dependent 11 beta-OHSD, respectively when 80 micrograms of enzyme protein was used. The inhibitory effects of gossypol on these two 11 beta-OHSD isoforms were different. The IC50 (95% confidence limits) were 50.2 (48.3-52.0) mumol of gossypol for NAD-dependent 11 beta-OHSD and 1143 (1098-1188) mumol of gossypol for NADP-dependent 11 beta-OHSD. The Ki was gossypol 96 mmol.L-1 for the former and 340 mmol.L-1 for the latter. CONCLUSION: The NAD-dependent 11 beta-OHSD is a more critical physiologic mechanism than NADP-dependent 11 beta-OHSD for hypokalemia caused by gossypol.

11-beta-Hydroxysteroid Dehydrogenases↗

[Quantitative electroencephalogram monitoring the depth of anesthesia during skin incision].

We investigated the EEG parameter changes of skin incision during different depth of sevoflurane/nitrous oxide analgesia. 65 ASA physical status I patients (aged 34 +/- 12 yr) scheduled for elective abdominal surgery were studied. The tracheal of each patient was intubated and the lungs were ventilated. Patients were randomly assigned to one of three groups. Anesthesia was maintained with 1% (group I n = 25), 1.5% (group II n = 20) or 2% (group III n = 20) end-tidal sevoflurane concentration in 66% nitrous oxide. Each of the concentration levels was maintained for at least 15 minutes before surgical incision. The EEG electrodes were placed on each patient in a front-oparietal montage (Fp1- A1, Fp2- A2) referred to Cz. EEG was recorded during 3-min period before incision. Hemodynamic variables were also monitored. Inadequate anesthetic depth was defined as patient movement in response to a 5-cm skin incision. The ventilation was controlled to maintain normocapnia (PETCO2 5 +/- 0.04 kPa). The data were analysed using ANOVA, liner correlation analysis and t-test. A significant difference between EEG parameters (SEF, BIS,) and skin incision responsive rate were found among the three concentration groups (P < 0.01). There were no difference of hemodynamics among the three groups. Patients who moved at incision also had significantly higher SEF, BIS leveles compared to non-movers (P < 0.01). Quantitative EEG determinants were correlated well with the end-tidal sevoflurane concentration and were a useful predictor of patient movement in response to skin incision during sevoflurane/nitrous oxide anesthesia.

Adolescent↗

Comparative dose-dependence study of FK506 and cyclosporin A on the rate of axonal regeneration in the rat sciatic nerve.

The new immunosuppressant drug FK506 (Tacrolimus) increases the rate of nerve regeneration in vivo (Gold et al., 1994; Gold et al., 1995). In the present study, we have examined the dose-dependence of FK506's ability to enhance nerve regeneration. In the first set of experiments, rats received daily s.c. injections of FK506 (2 mg/kg, 5 mg/kg or 10 mg/kg) for 18 days after a sciatic nerve crush injury. Signs of functional recovery in the hind feet appeared earlier than in saline-treated control rats at all three FK506 dosage; recovery was maximally accelerated in the 5-mg/kg group. Light microscopy at 18 days after nerve crush revealed more regenerating myelinated fibers in FK506-treated rats than in controls; this was most apparent in the 5-mg/kg group. Morphometric analysis of axonal areas in the soleus nerve confirmed that axonal calibers were maximally increased in the 5-mg/kg group. In the second set of experiments, the rate of axonal regeneration was determined by radiolabeling the L5 dorsal root ganglion. Regeneration rate for sensory axons was maximally increased (by 34%) in the 5-mg/kg group. In contrast, cyclosporin A (10 or 50 mg/kg; dosages were selected on the basis of the 1/10 lower potency of cyclosporin A) did not significantly alter the rate of axonal regeneration. Cyclosporin A (50 mg/kg) also failed to increase functional recovery or axonal calibers in the soleus nerve. Because the two drugs share a common mechanism for producing immunosuppression (i.e., calcineurin inhibition), these results indicate that FK506's nerve regenerative property involves a distinct, calcineurin-independent mechanism.

Animals↗

Prostitutes, prostitution and STD/HIV transmission in mainland China.

China's opening to the world has enabled massive social and economic transformations and the liberalization of many policies, but also the rise of coincident social problems and diseases. A revival of wide-scale female prostitution since the 1980s has now accelerated to a nationwide dilemma. Prostitutes have long been considered to be reservoirs, if not 'vectors' for the transmission of sexual diseases. A well established STD epidemic in the last decade, plus the presence of growing HIV infections in China now, underscore the need to evaluate the prostitute's role in STD and HIV propagation. This report examines unobtrusive data on female prostitutes in the People's Republic of China through an analysis of prison records from eight sexually segregated prisons (six in Sichuan Province and two in Guizhou Province), two female re-education institutions, and arrest records for convicted prostitutes from four counties in Sichuan Province and Chengdu City (also in Sichuan). Collectively, these data represent 2057 female prostitution cases, and span the years 1988-1990. Demographics are examined to enable a profile of the prostitute as based on data reviewed, and this is contrasted to the stereotype of the prostitute as described in government propaganda against prostitution. STD prevalence rates in the samples are examined and contrasted to two other studies on STDs in nonprostitution populations made available to the authors. Prostitute arrest records reveal a majority had active STD infection[s] at the time of their apprehension, with gonorrhea being the most common bacterium; in many instances, prostitutes also had a history of other sexually transmitted diseases. Thus, data examined support the notion of prostitution as an agent in STD transmission. Presence of HIV infection in prostitutes could not be corroborated through sampled records, nor could prostitution itself be confirmed as an agent in HIV transmission at present. However, given the type of clients serviced by prostitutes in China, a prostitute's own risk of HIV infection is discussed. Control measures by the Chinese government to curb prostitution are examined at both national and provincial levels. Questions are raised as to the effectiveness of present tactics as adjunctive strategies in reducing STD infection and HIV risk in the prostitution population.

China↗

Rat neutrophil defensins. Precursor structures and expression during neutrophilic myelopoiesis.

Defensins constitute a family of 3- to 4-kDa antimicrobial peptides that are stored in the cytoplasmic granules of neutrophils, some macrophages, and intestinal Paneth cells. We have assessed defensin gene expression during myeloid differentiation by first characterizing cDNAs for each of the four known rat neutrophil defensins (RatNP 1-4). The cDNA sequences revealed that the peptides are synthesized as 87-94 amino acid precursors, each containing signal, pro-, and mature peptide segments. RatNP-3 and -4 mRNAs, but not those for RatNP-1 and -2 or other myeloid defensins, contained unique polypurine tracts located close to the termination codon in the 3' untranslated region. By using cDNA probes and/or riboprobes, we evaluated defensin transcript levels in a variety of tissues and in the full spectrum of neutrophil precursors. By in situ hybridization, defensin mRNAs were localized to neutrophil precursors in the bone marrow, with the highest mRNA levels occurring in promyelocytes and somewhat lower signals occurring in myeloblasts and myelocytes. Defensin mRNAs were not detectable in bands or mature neutrophils, nor at significant levels in tissues other than bone marrow. The accumulation of defensin protein in bone marrow cells was assessed by immunohistochemical staining with anti-RatNP-1 Ab. RatNP 1-4 mRNAs and protein levels were then correlated for each stage of neutrophilic differentiation to reveal the maturational profile of myeloid defensin gene expression in the rat.

Amino Acid Sequence↗

Topical GM1 ganglioside to promote crushed rat sciatic nerve regeneration.

The effects of topical GM1 ganglioside on crushed rat sciatic nerve regeneration were studied in this presentation. Thirty-four rats, with 68 bilateral sciatic nerves, were divided into seven groups: one group of four rats for measurement of normal motor nerve conduction velocity (MNCV), three as controls, and another three in the GM1-treated groups. Sciatic nerves were exposed and crushed at a site 6 mm distal to the sciatic notch by the standard technique. In this manner, 3 mm wide crush injuries were created. Then 2.1 microliters of normal saline was injected into the crush site in the control groups and an equal volume of GM1 solution (containing 10 micrograms GM1) was injected into the GM1-treated groups. Electrophysiological, histological, and morphometric evaluations were carried out at 12, 28, and 56 days. A significantly higher muscle action potential (MAP) rate was found in the GM1-treated group (70%) vs. the controls (none) at 12 days (P < 0.005), and increased MNCV was found in the GM1-treated groups at both 28 and 56 days, especially at 56 days, when it was 39.59 +/- 9.23 m/sec vs. 31.42 +/- 4.07 m/sec in controls (P < 0.05). Morphometrically, there were more regenerated myelinated fibers (RMFs) at 12 days, and larger diameter of RMFs were observed at 12, 28, and 56 days in the GM1-treated groups.

Action Potentials↗

Effects of nerve growth factor on crushed sciatic nerve regeneration in rats.

The effects of nerve growth factor (NGF) on crushed sciatic nerve regeneration were studied in 30 rats, with 60 bilateral nerves. The nerves were crushed at a site 6 mm distal to the sciatic notch by the standard technique and 3 mm wide crush injuries were created. Then 2.1 microliters of normal saline in the control groups and an equal volume of NGF solution (containing 1 microgram of NGF) in the NGF-treated groups was injected into the crush sites and followed for 12, 28, and 56 days, respectively. At the end of the observation, electrophysiological evaluation was carried out; then samples 10 mm distal to the crush site were removed and prepared for histological and morphometric studies. Evoked muscle action potential (MAP) was recorded in 50% of the NGF-treated group at 12 days but not in the control group; the difference was statistically significant (P < 0.05). The motor nerve conduction velocity (MNCV) was increased in NGF-treated groups compared with control groups at 28 and 56 days (P < 0.05). Morphometrically, significantly more regenerated myelinated fibers (RMFs) were seen at 12 days, and larger diameter RMFs were found at 12, 28, and 56 days in NGF-treated groups than in control groups. These results indicate that topically applied NGF stimulates nerve regeneration and promotes function recovery in crushed rat sciatic nerves.

Action Potentials↗

Study of microvascular polyester prosthesis in rat carotid arteries.

The implantation of a microvascular polyester prosthesis (MPP) (internal diameter 1 mm, length 10 mm) in the carotid arteries was studied in 48 Sprague-Dawley rats. The left carotid artery was resected to 7 mm in length and replaced with MPP by means of sleeve anastomoses. Postoperatively the patency was monitored with Doppler ultrasound at 24 and 72 hr, and at 1, 2, 3, 4, 8, and 12 weeks and was confirmed either by direct inspection intraoperatively or by angiography at the time of removal. At each monitoring time, all the thrombosed and some selected patent grafts were removed and prepared for scanning electron microscopy (SEM) study. The early patency rate was 100% within 24 hr, and the cumulative long-term patency rate was 77.1% at 12 weeks. Rapid and complete endothelial lining (EL) restoration was demonstrated 3 weeks after operation, which provided a smooth and nonthrombogenic surface, and contributed to the long-term patency. Ten of the 11 failed grafts occurred within 3 weeks, that is, before EL, due to thrombosis. These observations indicate that MPP can be successfully used as arterial conduits in rats, and an enhanced patency rate may be expected with the use of anticoagulants or endothelial cell seeding for prevention of early thrombosis.

Animals↗

Facilitation of retinal function recovery by natural products after temporary ischemic occlusion of central retinal artery.

The b-wave of electroretinogram (ERG) was used as an indicator of the retinal function in this research to study the facilitation of retinal function recovery by some natural products isolated from medicinal plants. The retinal ischemia was induced by occlusion of the central retinal artery. It was found that the recovery of b-waves was limited to approximately 30-37% in control animals, whereas the b-wave recovery was doubled by natural products, including scoparone, corylifolinin and EGCG (epigallocatechin-3-0-gallate). Lespedeza flavanone A had biphasic action by suppressing the b-wave recovery below control level initially, then enhancing the b-wave recovery over the control rate later. These results indicate that some natural products could be used for the treatment of ischemic retinopathy.

Animals↗

The dynamic change of plasma endothelin-1 during the perioperative period in patients with rheumatic valvular disease and secondary pulmonary hypertension.

The arterial plasma endothelin-1 concentration was substantially more elevated in 15 patients with rheumatic valvular disease and secondary pulmonary hypertension than in healthy volunteers (3.66 +/- 2.20 versus 1.17 +/- 0.38 pg/ml, mean +/- standard deviation; p < 0.01). The preoperative plasma endothelin-1 level was highly correlated with the pulmonary hemodynamics: pulmonary artery systolic pressure (r = 0.94, p < 0.001), pulmonary artery mean pressure (r = 0.86, p < 0.001), pulmonary capillary wedge pressure (r = 0.82, p < 0.001), and pulmonary vascular resistance (r = 0.63, p < 0.02). After valve replacement, the plasma endothelin-1 concentration declined substantially and the pulmonary hemodynamics improved markedly. Two weeks after the operation, the plasma endothelin-1 level in patients (1.26 +/- 0.45 pg/ml, mean +/- standard deviation) was not statistically different from that in the healthy volunteers. The plasma endothelin-1 concentration continuously increased during the course of cardiopulmonary bypass and peaked after cessation of bypass. The peak plasma endothelin-1 level (13.49 +/- 4.60 pg/ml, mean +/- standard deviation) positively correlated with the bypass time (r = 0.64, p < 0.02) and negatively correlated with the urine volume during bypass (r = -0.69, p < 0.01). We conclude that (1) increased plasma endothelin-1 might be implicated in the pathogenesis of secondary pulmonary hypertension caused by rheumatic valvular disease and (2) markedly elevated plasma endothelin-1 concentrations might be associated with the mechanism of cardiac or renal dysfunction after prolonged cardiopulmonary bypass.

Adult↗

[Furacilin compound cream for profound frostbite].

Furacilin compound cream in the treatment of profound frostbite was studied. The results of animal experiment showed that furacilin cream might greatly reduce vascular permeability of frostbite. The average survival rate of frostbite tissue increased from 12.0 +/- 1.2% in the control group to 62.0 +/- 3.7% in the treated group. The difference between the two groups was statistically significant (P < 0.001). Five patients with profound frostbite were clinically treated with the cream with satisfactory results.

Adult↗

[Studies on constituents of Ilex chinensis Sims].

Several compounds characterised as protocatechuic acid, caffeic acid, syringin, rotundic acid and pedunculoside were isolated from the leaves of Ilex chinensis, a Chinese crude drug. A novel compound cyclohexanone pedunculosyl-3,23-O-acetal was identified and proposed as a pedunculoside derivative produced in the extracting procedure.

Caffeic Acids↗

[Distinguishing Anopheles dirus of Hainan Province by gas chromatography of cuticular hydrocarbons].

In order to identify the members of Anopheles dirus complex of Hainan Province an analysis of relative content of cuticular saturated n-paraffins of Anopheles dirus collected from different localities and in different months in Hainan Province was performed by using gas chromatography. The difference among the cuticular hydrocarbons n-paraffins components was statistically insignificant. The values of stepwise cluster analysis (Q model) were very close for all the collected populations. These data suggested that there might be one species of Anopheles virus complex which was further confirmed by the similarities between blood preference, seasonal variation, and nocturnal activity.

Animals↗