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Biomedical subjects

D H Zhao

Publications and source records attributed to D H Zhao.

At least 19 recordsLinked to original sources
PubMed2001

Delivery of glucocorticoid conjugate in rat gastrointestinal tract and its treatment for ulcerative colitis.

AIM: To evaluate colonic delivery and therapeutic effect of the newly synthesized dexamethasone (DX)-dextran (500 000) conjugate (DXD50) in the rat. METHODS: The amount of dexamethasone was measured in the contents from different parts of rat gastrointestinal tract and in plasma after ig conjugate. Therapeutic effect of conjugate and DX was tested in trinitrobenzenesulfonic acid-induced colitis in rat. Repair of colitis was assessed by measuring colonic ulceration area, colon weight, and colonic myeloperoxidase (MPO) activity. Systemic immunosuppression of DX was evaluated with weight of thymus and spleen and lymphocyte count in peripheral blood from rat with ulcerative colitis. RESULTS: Dexamethasone released from conjugate was mainly distributed in contents of cecum and colon. When DXD50 and DX 0.25 micromol . kg-1 . d-1 were used ig to treat ulcerative colitis in rat, the ulcerative area of colon was reduced by 55.6 % and 33.3 %, respectively whereas colon weight was reduced by 17.9 % and 2.6 %, respectively. The conjugate had no effect on lymphocyte count in peripheral blood, spleen weight, and thymus weight of rat which could be reduced markedly by the same dose of DX (P < 0.05 vs control). CONCLUSION: DXD50, which could specifically deliver DX to large intestine, is a promising agent in the treatment of human inflammatory bowel disease.

Animals↗
PubMed2001

[Synthesis of benzodihydropyran derivatives and evaluation of their preliminary biological activities on bone and vascular tissues].

AIM: To screen optimal drugs against postmenopausal osteoporosis with cardiovascular protective activities. METHODS: A series of benzodihydropyran derivatives were designed and synthesized in view of comprehensive observations of raloxifene and ipriflavone. The antiosteoporosis activities of compounds a-e (10(-7) mol.L-1) on the proliferation of human osteoblast cell HOS TE85 were studied. The cardiovascular protective activities were evaluated by observing their effects on proliferation of human vascular endothelium cell ECV-304 and their protective effects on ECV-304 damaged by H2O2. RESULTS: Their structures were determined by spectrums. Compounds a, b and c (10(-7) mol.L-1) were shown to significantly help proliferation of HOS TE85. In addition, b, d and e (10(-8) mol.L-1) helped proliferation of ECV-304 significantly. Compounds b and c (10(-6) mol.L-1) showed strong protective activity on ECV-304 damaged by H2O2. Compounds b and c shifted the KCl dose-response curves to the right and decreased the maximal response. CONCLUSION: Compounds b and c showed some bone and vascular protective activities which benefit postmenopausal and cardiovascular diseases.

Animals↗
PubMed2001

[Pharmacokinetics of site-specific delivery of dexamethasone-dextran prodrug in rat gastrointestinal tract].

AIM: To explore whether dexamethasone-dextran (260,000) has the characteristics of site-specific delivery in rat gastrointestinal tract. METHODS: Dexamethasone prodrug and dexamethasone were administered to rat ig at the dose of 5 mumol.kg-1. The distribution of dexamethasone in the contents and mucosa of different parts of the rat GI tract at different time intervals and its concentration in plasma were determined by HPLC. RESULTS: Dexamethasone was mainly released in the cecum and colon contents and mucosa after oral administration of dexamethasone prodrug. The absorption was reduced significantly. The peak time of the drug in plasma was 8.1 h, and the peak concentration was 32 micrograms.L-1. However, free dexamethasone was found mainly in the contents and mucosa of the stomach, proximal and distal small intestine. The peak time of the drug in plasma was 2.2 h, and the peak concentration was 2120 micrograms.L-1. CONCLUSION: Dexamethasone can be specifically delivered to the large intestine by using dexamethasone-dextran (260,000). It appears that the prodrug has a potential in the treatment of inflammatory bowel disease.

Animals↗
PubMed2000

Mitigation of endotoxin-induced acute lung injury in ventilated rabbits by surfactant and inhaled nitric oxide.

OBJECTIVE: To evaluate the efficacy of surfactant and inhaled nitric oxide (iNO) in endotoxin-induced acute lung injury (ALI). DESIGN: Prospective, randomised, controlled experimental study. SETTING: A medical university hospital research laboratory. INTERVENTION: Twenty-nine adult rabbits (2.4-3.4 kg) were given two doses of intravenous endotoxin (Escherichia coli) (0.01 mg/kg and, 12 h later, 0.1 mg/kg), and then subjected to mechanical ventilation. After 8 h these animals were allocated to four treatment groups: (1) control, (2) iNO at 20 ppm (NO), (3) surfactant at 100 mg/kg (Surf) and (4) both surfactant and iNO as in groups 2 and 3 (SNO), and ventilated for a further 6 h followed by broncho-alveolar lavage (BAL), analysis of surfactant contents in BAL fluid and histological examination of the lungs. MEASUREMENTS AND RESULTS: All the animals had developed ALI with respiratory failure 8 h after the second dose of endotoxin as evidenced by a decrease of PaO2/FIO2 from 520 +/- 30 to 395 +/- 19 mmHg and dynamic compliance (Cdyn) from 1.20 +/- 0.11 to 0.73 +/- 0.05 ml/ cmH2O x kg, and an increase of intrapulmonary shunting (Qs/Qt) from 7.5 +/- 0.8% to 12.9 +/- 1.0% (all measurements p < 0.01 versus baseline). In the SNO group, values for PaO2/FIO2, Cdyn and Qs/Qt after 6 h were 301 +/- 15 mmHg, 0.67 +/- 0.05 ml/cmH2O x kg and 16.5 +/- 0.8%, compared to 224 +/- 26 mmHg, 0.53 +/- 0.04 ml/ cmH2O x kg and 24.1 +/- 2.0%, respectively, in the control group (all measurements p < 0.01). Both Surf and NO groups showed intermediate levels of these parameters. In both Surf and SNO groups, the minimum surface tension of BAL fluid was lower, and the content of disaturated phosphatidylcholine/total protein higher, than in the control and NO groups (p < 0.01). Histological features of lung injury were less prominent and wet/dry lung weight ratio lower in the NO, Surf and SNO groups. Decreased surfactant protein A (SP-A) and its mRNA expression were found in all endotoxin-exposed groups, but the SP-A content of the SNO group was moderately improved in comparison to the control group. Surfactant aggregate size was not affected. CONCLUSION: Early application of surfactant and iNO moderately mitigated ALI as reflected by improvement of lung mechanics, pulmonary perfusion and morphology.

Administration, Inhalation↗
PubMed2000

Effects of MN-9202 on platelet aggregation, 5-HT release, TXB2 synthesis, and calcium mobilization in rabbit platelets in vitro.

AIM: To study the effects of MN-9202, a new effective Ca2+ channel blocker, on platelet aggregation, 5-HT and TXB2 release, and calcium transport induced by platelet activators. METHODS: The mobilization of cytosolic-free calcium induced by thrombin in washed platelets was observed by Ca(2+)-sensitive fluorescent indicator, Fura-2 AM and time scan measurement. Aggregation induced by ADP and thrombin in rabbits citrate platelet-rich plasma (PRP) was measured by aggregometer. 5-HT and TXB2 were assayed by HPLC/ECD and RIA, respectively. RESULTS: MN-9202 inhibited platelet aggregation induced by ADP and thrombin in a concentration-dependent manner. MN-9202 1 mumol.L-1 inhibited release of 5-HT in PRP induced by collagen at 15 mg.L-1 (113 +/- 15 vs 178 +/- 18, P < 0.05), however, MN-9202 did not have effect on 5-HT secreted by high dose of collagen. MN-9202 0.1 and 1 mumol.L-1 blocked extracellular calcium influx and sarcoplasmic calcium release, and the suppression on extracellular calcium influx was more obvious. Furthermore, treatment with MN-9202 0.01, 0.1, and 1 mumol.L-1 markedly decreased ADP-induced TXB2 (pg/10(8) platelet) release from PRP (906 +/- 200, 881 +/- 131, and 793 +/- 169 vs 1264 +/- 202, P < 0.01). CONCLUSION: MN-9202 acts as an effective Ca2+ antagonist and blocks platelet activation by inhibiting platelet Ca2+ influx and arachidonic acid metabolism.

Animals↗
PubMed1996

Pharmacokinetics of m-nifedipine in rabbits after intravenous injection.

AIM: To study the dose effects on pharmacokinetics of m-Nif. METHODS: Fifteen rabbits were divided into 3 groups receiving i.v. m-Nif 0.5, 1, and 2 mg.kg-1. Plasma levels of m-Nif were determined with HPLC method. RESULTS: The concentration-time data were fitted with 2-compartment model. After i.v. 1 mg.kg-1, the parameters were: Vd = 0.37 +/- 0.10 L.kg-1, T1/2 alpha = 6.4 +/- 2.9 min, T1/2 beta = 84 +/- 22 min, AUC = 94 +/- 16 mg.min.L-1, Cl = 0.65 +/- 0.13 L.kg-1.h-1. No statistically significant difference was found in Cl and T1/2 beta between 3 dose groups. AUC (standardized to body weight) was correlated with doses. CONCLUSIONS: m-Nif was distributed widely and eliminated at a fairly rapid rate in the rabbits. No dose-dependent pharmacokinetics was found after i.v. m-Nif 0.5-2 mg.kg-1. m-Nifedipine, 2, 6-dimethyl-3, 5-dicarbomethoxy-4-(3'-nitrophenyl)-1, 4-dihydropyridine (m-Nif) is a new calcium channel blocker. Dihydropyridine calcium channel antagonists are mainly used for the treatment of hypertension and angina[1]. Nifedipine is susceptible to photodegradation, but m-Nif is stable when exposed to light. The 2 drugs have the same antihypertensive effect[2]. So far, no report has been found on pharmacokinetics of m-Nif. Using a high performance liquid chromatographic (HPLC) method, we studied the dose effects on the pharmacokinetics of i.v. m-Nif 0.5, 1, and 2 mg.kg-1 in conscious rabbits.

Animals↗
PubMed1995

Effects of isoprenaline on delayed rectifier potassium current in isolated guinea pig ventricular myocytes.

AIM: To study the effects of isoprenaline (Iso) on the delayed rectifier potassium current (Ik) in isolated guinea pig ventricular myocytes. METHODS: Single cells were isolated from guinea pig ventricle. Ik was studied under voltage clamp conditions. RESULTS: When Ik was activated by depolarizing pulses to +40 mV of increasing duration (40-300 ms), Iso 1 mumol . L-1 caused an enhancement in Ik which was larger for longer pulses (150-300 ms). This was also seen when the intracellular calcium was buffered by 1,2-bis(2-aminophenoxy) ethane-N, N, N1, N1-tetraacetic acid (BAPTA). Intracellular application of BAPTA caused a decrease in Ik activated by longer pulses. CONCLUSION: There were two components of Ik, one of which was modulated by Iso and intracellular Ca2+.

Animals↗
PubMed1994

[The changes in copper contents and its clinical significance in patients with liver cirrhosis and hepatocarcinoma].

Copper contents (Cu) in bodies and serum ceruloplasmin (Cp) were assayed in patients with liver cirrhosis (LC) and hepatocarcinoma (HCC) with atomic absorption and other methods. The results were shown as follows: 1. The mean levels of serum Cp and urine Cu in LC were higher than those of normal (P < 0.05 and 0.01). 2. Serum Cu and Cp levels were consistently high in HCC. Urine Cu level was also elevated and had positive correlation with that of serum Cu (r = 0.567, P < 0.01). 3. Cirrhotic liver Cu content was almost the same as that of pericarcinomatous liver Cu, being higher than that of normal and carcinomatous liver. 4. Hair Cu level in both LC and HCC was apparently lower than that of normal subjects. 5. Serum Cu level in patients with tumor more than 5 cm in size was higher than that in patients with tumor less than 5 cm (P < 0.05). 6. Serum Cu level decreased along with the reduction of tumor size after treatment. 7. Serum Cu and Cp levels may be used as markers for detection of HCC, especially for AFP-negative HCC. Serum Cu estimation is valuable in assessment of the therapeutic effect and prognosis in patients with HCC.

Adolescent↗
PubMed1993

Protective effects of 3,6-dimethylamino-dibenzopyriodonium edetate on global ischemia reperfused isolated rat hearts.

The effects of 3,6-dimethylamino-dibenzopyriodonium edetate (IHC-72) on global ischemia reperfused rat hearts were investigated. In the isolated working rat heart, 40-min global ischemia followed by 30-min reperfusion resulted in increases of ventricular tachycardia (VT) and ventricular fibrillation (VF), increases of creatine kinase (CK) release and malondialdehyde (MDA) contents, but decreased superoxide dismutase (SOD) activity. Following ischemia and reperfusion, the accumulation of myocardial calcium increased. IHC-72 50 mumol.L-1 given 10 min before ischemia and during reperfusion decreased the cardiac CK release, VT, and VF, reduced the MDA contents, prevented the reduction of SOD activity and attenuated the accumulation of myocardial calcium and sodium vs control. These results indicated that IHC-72 protected myocardial reperfused injury.

Animals↗
PubMed1993

Effects of 3,6-dimethylamino-dibenzopyriodonium edetate on action potentials in guinea pig papillary muscles.

The effects of 3,6-dimethylamino-dibenzopyriodonium edetate (IHC-72) on action potentials (AP) and slow response action potentials of guinea pig papillary muscles were studied with intracellular microelectrodes. IHC-72 12.7, 25.4, and 50.8 mumol.L-1 decreased the maximal upstroke velocity (Vmax), amplitude of action potential (APA), over shot (OS), and resting potential (RP) while prolonged the action potential duration at 30%, 50%, 90%, and 100% repolarization (APD30, APD50, APD90, and APD100). IHC-72 25.4 and 50.8 mumol.L-1 decreased the APA, Vmax, and prolonged APD50 and APD90 under high K+ superfusion. IHC-72 25.4 and 50.8 mumol.L-1 depressed the automaticity, APA, and maximal diastolic potential (MDP) of the slow response action potentials induced by BaCl2. The results indicated that IHC-72 might nonspecifically inhibit the transmembrane movement of Ca2+, Na+, and K+.

Action Potentials↗
PubMed1993

[Effects of furyl-dihydropyridine on action potential ventricular myocardium of rabbit in vivo and isolated guinea pig left atrium in vitro].

Effects of furyl-dihydropyridine (FDP) on action potential of rabbit ventricular myocardium in vivo were observed with floating microelectrode technique. FDP 0.5 mg.kg-1 i.v. increased APD30 from 104 +/- 7 to 127 +/- 7 ms, APD90 from 146 +/- 10 to 177 +/- 9 ms (P < 0.01, n = 7), decreased the heart rate from 230 +/- 18 to 203 +/- 20 bpm (P < 0.05). Nifedipine (Nif) 0.5 mg.kg-1 i.v. reduced APD and increased the HR in rabbit. In guinea pig left atrium, FDP and Nif decreased the APD, the effects of acetylcholine to shorten the APD was antagonized by FDP 1 mumol.L-1. In rabbit's sinoatrial nodes, FDP 0.5, 1 mumol.L-1 also suppressed the APA and increased the spontaneous sinus cycle length (SCL) and APD50. These results indicate that FDP may inhibit the Ca2+ and K+ currents of myocardium.

Acetylcholine↗
PubMed1992

DNA content and its relationship with pathology and prognosis of colorectal carcinoma.

The DNA content of 181 colorectal cancers was investigated by flow cytometry on paraffin-embedded specimen. The relationship of flow cytometric DNA patterns of colorectal cancer to Dukes's stage, histological type and grade, tumor size and patient's prognosis were analysed. The DNA aneuploid carcinomas were found in 53.04% of the patients (hypodiploid 22.10%, hyperdiploid 20.99%, polyploid 9.94%). Diploidy was found in 46.96% of the patients with colorectal cancer. The proportions of aneuploidy were significantly lower in the patients with Dukes' stage A (25.00%) and B (47.14%) than those with Dukes' stage C (64.71%) and D (68.42%). Aneuploid frequency was higher in the patients with poorly differentiated adenocarcinoma (84.62%), mucinous adenocarcinoma (62.50%) and tubular adenocarcinoma (52.75%) than those with villous adenocarcinoma (22.86%). The proportion of aneuploidy was significantly higher in the patients with poorly differentiated tumor (71.79%) than in those with moderately (50.00%) and well differentiated tumors (44.83%). Five-year survival rate of the patients with DNA aneuploid tumors was 33.80% compared with 66.67% of those with diploid tumors. Analysis of Cox regression revealed that DNA ploidy and Dukes' stage significantly influenced the patient's prognosis. It is suggested that DNA ploidy might be an important prognostic factor in colorectal cancer.

Adenocarcinoma↗
PubMed1992

[Comparison of antiarrhythmic effects of IHC-72 (an iodonium-72), lidocaine and verapamil].

The antiarrhythmic actions of 3,6-dimethylamino-dibenzopyridonium edetate (IHC-72), lidocaine (Lid) and verapamil (Ver) on several models Were compared at equitoxic doses (equal fraction of LD50). The action of IHC-72 against aconitine induced arrhythmia was similar to that of Lid but stronger than that of Ver in anesthetized rats. The effect of IHC-72 on ouabain induced arrhythmia was also similar to that of Lid, but weaker than that of Ver in anesthetized guinea pigs. The activity of IHC-72 to raise electrical ventricular fibrillation thresholds (VFT) was weaker than that of Lid and Ver. The effects of IHC-72 in decreasing the incidence of ventricular premature beat(VP B), ventricular tachycardia (VT), ventricular fibrillation (VF) and shortening the duration of VT yielded by reperfusion were similar to those of Lid anf Ver in vivo.

Aconitine↗
PubMed1991

[Effects of furyl-dihydropyridines I on lipid peroxides of ischemic myocardium and ATPases activity of erythrocyte membranes in rats].

Acute myocardial ischemia and reperfusion in rats increased glutamic oxalacetic transaminase (GOT), non-esterified fatty acid (FFA), malondialdehyde (MDA) content. Furyl-dihydropyridines I 10 mg.kg-1 decreased the release of GOT, FFA, MDA of ischemic myocardium, and prevent ischemia-reperfusion arrhythmia. Furyl-dihydropyridines I increased Na, K-ATPase activity and N-acethylneuraminic acid (NANA) content of erythrocyte membranes, inhibited Ca-ATPase activity of erythrocyte membranes in rats. The results suggested that the mechanism of protecting the ischemic-reperfused myocardium might be associated with the inhibition of cellular lipid peroxidation and Ca-ATPase activity of cell membranes.

Animals↗
PubMed1991

Positive inotropic effect of apomorphine on guinea pig myocardium is mediated by dopamine DA1 receptors.

Dopaminergic agonist apomorphine (Apo, 1-100 mumol.L-1) had a concentration-dependent positive inotropic effect on guinea pig left atria. This effect was not changed obviously when the influences of sympathetic and parasympathetic nerves were eliminated by reserpine and atropine, respectively. Apo had little inotropic action on guinea pig papillary muscles. The time course of positive inotropic effect of Apo was different from that of isoprenaline and phenylephrine. Apo influenced the isometric contraction curves in a different way from isoprenaline. Dopaminergic antagonist haloperidol antagonized the positive inotropic effect of Apo. This effect was also competitively antagonized by dopamine DA1 antagonist SCH 23390. While dopamine DA2 antagonist domperidone, beta-adrenergic antagonist propranolol and alpha-adrenergic antagonist phentolamine did not obviously influence the effect of Apo. We concluded that the positive inotropic effect of Apo was mediated by postsynaptic dopamine DA1 receptors in guinea pig left atria.

Animals↗
PubMed1991

Prevention of global myocardial reperfusion injury on isolated rabbit hearts with furyl-dihydropyridines I.

In the isolated rabbit heart of recirculating nonpulsatile perfusion circuit, furyl-dihydropyridines I 20 mumol.L-1 greatly reduced the leakage of myocardial enzymes and the concentration of malondialdehyde (MDA) in plasma, decreased the myocardial calcium and sodium contents, maintained normal coronary vascular resistance and prevented reperfusion arrhythmias of global postischemic reperfusion hearts. Its mechanism of protecting the ischemic-reperfused myocardium might be associated with the diminution of calcium influx of myocardial cells and cellular lipid peroxidation induced by oxygen free radicals.

Animals↗