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Biomedical subjects

G R Li

Publications and source records attributed to G R Li.

At least 55 records · Page 3Linked to original sources
PubMed1995

Contribution of ATP-sensitive potassium channels to the electrophysiological effects of adenosine in guinea-pig atrial cells.

1. Adenosine caused dose-dependent action potential abbreviation in multicellular guinea-pig atrial preparations, an action antagonized by glyburide (IC50, 31 microM) in both physiological and low-chloride superfusate. 2. When 5 mM ATP was included in pipettes for whole-cell voltage clamp of isolated guinea-pig atrial myocytes, adenosine (10 microM) increased the holding current at -40 mV from 41 +/- 8 to 246 +/- 31 pA (mean +/- S.E.M., P < 0.01), and glyburide (20 microM) returned the holding current to 69 +/- 11 pA (P < 0.01 vs. adenosine alone). Acetylcholine (10 microM) also increased the holding current, but its effects were not altered by glyburide. 3. Both adenosine and acetylcholine induced an additional current component in response to 500 ms voltage steps. Glyburide partially inhibited the adenosine-induced current, but did not alter the effect of acetylcholine. In the presence of maximally effective acetylcholine concentrations, adenosine increased membrane conductance (P < 0.01), although to a lesser extent than in the absence of acetylcholine. 4. Single K+ channel activity was seen in only one of eight cell-attached patches in the absence of adenosine or acetylcholine (0.5 mM Ba2+ in bath and pipette solutions). With acetylcholine (10 microM) in the pipette, inwardly rectifying channels (conductance, 41 +/- 5 pS) were seen in five of six patches. With adenosine (10 microM) in the pipette, single-channel activity was seen in twelve of fourteen patches with two populations of channels, one similar to that induced by acetylcholine and another higher-conductance channel (72 +/- 5 pS) that showed less inward rectification. Glyburide (20 microM) suppressed the high-conductance channel (68 +/- 2 pS) leaving a single channel type with a conductance of 36 +/- 5 pS and strong inward rectification. 5. We conclude that K+ATP channels contribute to the electrophysiological actions of adenosine on guinea-pig atrium in the presence of physiological intracellular ATP levels, and may therefore play a role in the cardiac electrophysiological effects of adenosine in the absence of myocardial ischaemia.

Acetylcholine↗
PubMed1995

Calcium currents in ventricular myocytes of prehypertrophic cardiomyopathic hamsters.

Possible changes in Ca2+ currents (ICa), which might contribute to Ca2+ overload in young (70- to 100-day-old) cardiomyopathic (CM) hamster hearts, were determined in isolated ventricular myocytes with conventional recording and discontinuous single-electrode voltage-clamp techniques. Action potential duration at 90% repolarization (APD90) was significantly longer in CM myocytes compared with normal cells (APD90 = 120.3 +/- 4.5 vs. 98.2 +/- 5.9 ms, P < 0.01). Input resistance, membrane time constant, and membrane capacitance were similar in normal and CM myocytes. Current-voltage (I-V) relations for peak ICa were depressed in CM cells compared with normal cells; this difference was statistically significant at the peak of the I-V curve. Activation and inactivation relations for ICa and recovery from inactivation were similar in myocytes from normal and CM hearts. These changes occurred in myocytes from young CM animals before development of heart failure. Results indicate that increased Ca2+ influx through L-type Ca2+ channels does not account for the longer APD in cardiomyopathy and is not involved in the development of Ca2+ overload in cardiomyopathy.

Action Potentials↗
PubMed1995

Comparative mechanisms of 4-aminopyridine-resistant Ito in human and rabbit atrial myocytes.

The cardiac transient outward current (Ito) has been shown in several species to consist of two components: 1) a 4-aminopyridine (4-AP)-sensitive component (Ito1) and 2) a 4-AP-resistant component (Ito2). In rabbits, Ito2 is a Ca(2+)-dependent Cl- current [ICl(Ca)]; similar mechanisms have been suggested to underlie Ito2 in human atrium. We used whole cell patch-clamp techniques to define the mechanism of Ito2 (defined as the component resistant to 5 mM 4-AP) in human atrial myocytes, with parallel experiments performed in rabbit atrial cells. In rabbit atrium, Ito2 activated more slowly than Ito1 and had a bell-shaped current-voltage of Ito with properties similar to Ito2 in the rabbit, and a similar component recorded with pipette K+ replaced by Cs+ was suppressed by the substitution of methanesulfonate for Cl- in the superfusate. In human cells, a 4-AP-resistant Ito2 was recorded at a depolarizing pulse frequency of 1 Hz, but not at 0.1 Hz. Ito2 activated rapidly and inactivated earlier than Ito1, whereas its I-V relation was linear like that of Ito1. Ryanodine had no effect on human atrial Ito. When K(+)-free pipette solutions were used, no Ito was recorded in 30 human atrial myocytes, and external Cl- replacement with methanesulfonate failed to reveal an Ito. In 13 human myocytes, isoproterenol increased ICa but failed to activate an Ito compatible with ICl(Ca). Whereas caffeine suppressed human atrial Ito, it also suppressed Ito1 [in the presence of 200 microM Cd2+ to block ICa and 5 mM intracellular ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid to buffer intracellular Ca2+] in both human and rabbit atrium, indicating an action unrelated to Ca(2+)-triggered Ca2+ release. In conclusion, we were unable to demonstrate the presence of ICl(Ca) in human atrial myocytes, and the 4-AP-resistant component of Ito appeared to be due to 4-AP unblocking.

4-Aminopyridine↗
PubMed1992

Effects of allopurinol on reperfusion arrhythmias in isolated ventricles.

Electrophysiological effects of allopurinol on arrhythmias were studied in isolated segments of guinea pig right ventricular free walls paced from endocardium. A high-gain electrocardiogram as well as transmembrane electrical activity from endo- and epicardium were recorded. Tissues were exposed to simulated ischemia for 15 min and then were reperfused with normal Tyrode solution. Sustained or nonsustained ventricular tachycardia, bigeminy, and trigeminy with characteristics of transmural reentry occurred in early reperfusion in 75% of 20 control preparations. Arrhythmias were associated with prolongation of transmural conduction time and abbreviation of endocardial effective refractory period (ERP). Allopurinol strongly reduced the incidence of reperfusion arrhythmias (20-33%) between 10 and 100 microM, whereas either lower or higher concentrations (5 or 500 microM) were less effective (43 and 50%). Antiarrhythmic efficacy correlated with significant attenuation of reperfusion-induced transmural conduction delay (P less than 0.05 or 0.01). Allopurinol did not affect endocardial conduction times nor did it significantly alter endocardial action potential duration or ERP. Our results indicate that allopurinol exerts antiarrhythmic efficacy during reperfusion by selectively attenuating defects related to anisotropic tissue properties.

Action Potentials↗
PubMed1992

Verapamil prevents slowing of transmural conduction and suppresses arrhythmias in an isolated guinea pig ventricular model of ischemia and reperfusion.

Transmembrane electrical activity was recorded from endocardium and epicardium of isolated segments of guinea pig right ventricular free walls. An electrocardiogram was recorded by electrodes at opposite ends of the tissue bath. Endocardium was stimulated. Tissues were exposed to "ischemic" conditions (e.g., acidosis, hyperkalemia, hypoxia, and lactate) for 15 minutes and then were reperfused with "normal" Tyrode's solution. Arrhythmias with characteristics of transmural reentry occurred in ischemic conditions and early reperfusion in 30% and 70% of 20 control hearts, respectively. Arrhythmias were associated with prolongation of transmural conduction time (CT) and abbreviation of endocardial effective refractory period. Verapamil significantly suppressed reperfusion arrhythmias at 0.1-1.0 microM but not at 3.0 microM. Verapamil also significantly decreased the incidence of arrhythmias during ischemic conditions at 0.5 microM but significantly promoted ischemic arrhythmias at 3.0 microM. Action potential duration and effective refractory period were not altered by verapamil during ischemic conditions or reperfusion. However, at 0.1-1.0 microM, verapamil prevented or attenuated prolongation of transmural CT by ischemic conditions and reperfusion. Transmural CT was further prolonged at 3 microM verapamil. In epicardial slices, 1 microM verapamil shortened CT transverse to fiber orientation during reperfusion but had no effect on longitudinal CT. Our results indicate that verapamil may suppress arrhythmias through differential effects on CT transverse and longitudinal to fiber orientation in anisotropic ventricular tissues and thus by specifically improving transmural conduction.

Action Potentials↗
PubMed1991

Effects of quinidine on arrhythmias and conduction in an isolated tissue model of ischemia and reperfusion.

Transmembrane electrical activity from endo- and epicardium and a high-gain ECG were recorded from isolated segments of guinea pig right ventricles. Endocardium was stimulated. Tissues were exposed to ischemic conditions for 15 min and then reperfused with "normal" Tyrode's solution. Ventricular tachycardia, bigeminy, or trigeminy with characteristics of transmural reentry occurred in early reperfusion in 68% of control hearts. Arrhythmias were associated with prolongation of the transmural conduction time (CT) and abbreviation of the endocardial effective refractory period (EP). Quinidine significantly suppressed reperfusion arrhythmias at 1 and 5 microM, slightly increased the incidence of arrhythmias at 10 microM, and again suppressed arrhythmias at 50 and 100 microM. At 1 and 5 microM, quinidine prevented or attenuated prolongation of the transmural CT by ischemic conditions and reperfusion. The transmural CT was not significantly changed at 10 microM, and was further prolonged at 50 and 100 microM quinidine. The endocardial ERP was prolonged by 50 and 100 microM quinidine during ischemic conditions and reperfusion. In epicardial slices, 5 microM quinidine shortened the CT transverse to the fiber orientation during reperfusion but had no effect on the longitudinal CT. Thus, antiarrhythmic efficacy of low concentrations of quinidine may occur through differential effects dependent on tissue anisotropy.

Action Potentials↗
PubMed1991

Effects of isocorydine on action potentials in isolated canine Purkinje fibers and ventricular muscles.

Standard microelectrode techniques were used to study the effects of isocorydine (Isoc) on potential characteristics of canine cardiac Purkinje fibers (PF) and ventricular myocardium (VM) in vitro. In PF, the action potential durations (APD), APD50, and APD90, were prolonged at 3 mumol.L-1 but shortened at 30 mumol.L-1 by Isoc. The action potential amplitude (APA) and the maximal upstroke velocity (Vmax) were decreased at 100 mumol.L-1. In VM, the action potential characteristics were changed by Isoc at above 30 mumol.L-1. APD50 was shortened by APD90 was prolonged. Vmax were decreased at 30 mumol.L-1. The effective refractory period (ERP) was prolonged by Isoc in PF and VM. The results suggest that Isoc may interfere with K+, Na+, and Ca2+ currents in myocardiac cell membrane at different concentrations.

Action Potentials↗
PubMed1991

Induction of dormant HIV-1 by sodium butyrate: involvement of the TATA box in the activation of the HIV-1 promoter.

Reactivation of latent HIV-1 is believed to play a major role in the pathogenesis of AIDS. Here we show that sodium butyrate (NaB), which can cause gene induction or cell differentiation, reactivates dormant HIV-1 in vitro in chronically infected cells of T-lymphoid and monocytoid origin. The effect of NaB on HIV-1 expression in T-lymphoid cells was apparent 3 h after addition of drug and peaked at 24 h. During this time the proportion of HIV-1 antigen expressing cells increased from less than 0.5 to greater than 90%, and virus production increased by three orders of magnitude. The virus released by the NaB-induced cells was infectious. The extent and kinetics of NaB effects were similar to effects of phorbol 12-myristate 13-acetate in T cells, but not monocytes. Transient expression assays using an indicator gene under the control of the HIV-1 long terminal repeat revealed that mutations which altered the nucleotide sequence in the TATA box significantly reduced the NaB effect. These data show that NaB is a potent inducer of dormant HIV-1 and suggest that the TATA motif is required for this activity.

Butyrates↗
PubMed1991

Effects of lidocaine on reperfusion arrhythmias and electrophysiological properties in an isolated ventricular muscle model of ischemia and reperfusion.

Transmembrane electrical activity was recorded from endo- and epicardium of isolated segments of guinea pig right ventricles with standard microelectrode techniques. An ECG was also recorded by two electrodes placed at opposite ends of the tissue bath. Regular stimulation was delivered to the endocardium. Tissues were exposed to simulated ischemia for 15 min and then were reperfused with "normal" Tyrode's solution. Rapid sustained or nonsustained ventricular tachycardia, bigeminy or trigeminy with characteristics of transmural reentry occurred in early reperfusion in 14 of 20 hearts (70%). Arrhythmias were accompanied by prolongation of transmural conduction time and abbreviation of endocardial effective refractory period. With lidocaine, at 1, 5, 10 and 50 microM, reperfusion arrhythmias occurred in 53.3, 22.2, 20.8 and 14.3% of hearts, respectively. The decreased incidence of arrhythmias was statistically significant for 5 to 50 microM lidocaine (P less than .01). The antiarrhythmic effect did not correlate with changes in transmural conduction time, endocardial effective refractory period, or endocardial excitability. However, antiarrhythmic concentrations of lidocaine selectively depressed epicardial excitability and significantly increased endo- to epicardial conduction block during late ischemic and early reperfusion periods. Epicardial inexcitability extended to late diastole and conduction block was not restricted to premature beats. Thus, in transmural reentry in which the epicardium is an essential component of the circuit, lidocaine may interrupt the circuit by selectively rendering this component inexcitable.

Action Potentials↗
PubMed1990

The effect in vitro of 2'-deoxycytidine on the metabolism and cytotoxicity of 2',3'-dideoxycytidine.

We examined in vitro the effect of high, but clinically achievable and non-toxic, concentrations of 2'-deoxycytidine (dCyd) (greater than or equal to 100 mumols/l on the metabolism and cytotoxicity of 2',3'-dideoxycytidine (DDC) in normal human bone marrow mononuclear cells (BMMCs) and a cultured T-lymphocyte (HUT-102) cell line. Colony formation in semi-solid medium by bone marrow progenitor cells (CFU-GM and CFU-GEMM) was significantly protected by dCyd against the cytotoxic effects of high doses of DDC. In contrast, in HIV-infected HUT-102 cells, anti-HIV effect of DDC (10 mumols/l) was preserved in the presence of 100 mumols/l dCyd but partially reversed by higher levels of dCyd. dCyd reduced the generation of DDC triphosphate (DDC-TP) relative to dCyd triphosphate (dCTP) pools to a significantly greater extent in BMMCs versus HUT-102 cells. This might explain dCyd-mediated abrogation of DDC cytotoxicity against marrow progenitor cells with relative preservation of its anti-HIV-1 activity in HUT-102 cells.

Cell Line↗
PubMed1990

[Effects of neferine on heart electromechanical activity in anaesthetized cats].

Neferine, an alkaloid extracted from the green seed embryo of Nelumbo nucifera Gaertn, has been shown to have anti-arrhythmic action. Neferine 1-10 mg/kg iv dose-dependently decreased the monophasic action potential amplitude (MAPA), prolonged the monophasic action potential duration (MAPD). It also decreased LVP, dP/dt, prolonged SCL, and reduced arterial blood pressure in a dose-dependent manner. These effects were similar to those of quinidine, and different from tetrandrine. The latter had an inhibitory effect on LVP and dP/dt, but had no influence on MAPA and MAPD. The results indicate that neferine and quinidine have similar effects on heart electro-mechanical activity.

Action Potentials↗
PubMed1989

2'-Deoxycytidine protects normal human bone marrow progenitor cells in vitro against the cytotoxicity of 3'-azido-3'-deoxythymidine with preservation of antiretroviral activity.

Bone marrow cytotoxicity of 3'-azido-3'-deoxythymidine (AZT), an anti-human immunodeficiency virus (anti-HIV) drug, has been attributed to deoxyribonucleotide pool perturbations that might result in impaired DNA synthesis in normal bone marrow elements. We examined, in vitro, the effect of high, but clinically achievable and nontoxic, concentrations of 2'-deoxycytidine (dCyd) (greater than or equal to 100 mumol/L) on high-dose AZT mediated growth inhibition and intracellular biochemical perturbations in normal bone marrow progenitor cells. Colony formation by bone marrow progenitor cells in semisolid medium was significantly protected by dCyd against the inhibitory effects of co-administered, high concentrations of AZT (10 mumol/L). Also, dCyd significantly corrected AZT mediated depletion of intracellular thymidine triphosphate (dTTP) and dCyd triphosphate (dCTP) levels in normal bone marrow mononuclear cells (BMMC). Moreover, dCyd reduced the intracellular accumulation of AZT triphosphate (AZT-TP) and its DNA incorporation in BMMC. In contrast, co-administration of dCyd (100 mumol/L to 1 mmol/L) did not reverse AZT (10 mumol/L) mediated suppression of HIV infectivity in HUT-102 cells in culture, although a partial reduction in intracellular AZT-TP pools and its DNA incorporation as well as a correction of AZT mediated depletion of dTTP and dCTP pools was observed in these cells. These studies suggest that dCyd at high concentrations might ameliorate the bone marrow cytotoxicity of high-dose AZT without impairing its anti-HIV effect.

Bone Marrow↗
PubMed1989

[Light and electron microscopic studies of relationship between colon carcinoma and schistosomiasis].

The light and electron microscopic observations were carried out in 50 cases of colon specimens. No remarkable morphologic differences were found between the epithelial cells of the mucosa with schistosomiasis, colitis and the normal specimens. Cells of the colon carcinoma also showed no significant difference from those of the colon carcinoma associated with schistosomiasis. Atypical changes in the epithelial cells were not seen in the areas both adjacent to and remote from the carcinoma and in the egg deposit areas. Under LM, changes were manifested in various degrees in degeneration and disassociation of mucosal cells in colitis (1), schistosomiasis (1) and carcinoma associated with schistosomiasis (8). Under EM, changes in mucosal muscle cells were seen in colon carcinoma (2) and carcinoma associated with schistosomiasis (5). Proliferation of fibroblasts and hyperchromasia of the nuclei were noted in 3 cases of carcinoma associated with schistosomiasis. The pathological changes mentioned above were more prominent in cases of carcinoma associated with schistosomiasis than in those of colon carcinoma alone. The authors believed that the cause was non-specific changes induced by the toxin of the egg mechanical effects rather than a direct carcinogenic action of the eggs, and that the non-specific changes implied no direct relationship between the development of colon carcinoma and schistosomiasis.

Adenocarcinoma↗
PubMed1989

[Effects of neferine on transmembrane potentials of guinea pig myocardium].

Neferine, an alkaloid first isolated from the seed embryo of Nelumbo nucifera Gaertn in China, possesses an anti-arrhythmic action. The effects on the action potential duration (APD) and the maximal upstroke velocity (Vmax) in different driving rates, the slow response action potentials of K+-depolarized ventricular myocardium and the ouabain-induced oscillatory potentials were studied in guinea pig papillary muscles. Neferine 10 and 50 mumols/L markedly suppressed the transmembrane potentials Vmax at 0.1-5 Hz. It (50 mumols/L) prolonged the APD at 0.5-5 Hz. Neferine 10-100 mumols/L inhibited the contractility, amplitude of action potentials and Vmax of K+-depolarized guinea pig papillary muscles in a concentration-dependent manner, and 100 mumols/L decreased the amplitude of action potentials and Vmax from 73 +/- 7 mV and 6.0 +/- 1.7 V/s of control to 57 +/- 4 mV and 3.2 +/- 0.7 V/s, respectively. In addition, neferine 50 mumols/L abolished the oscillatory potentials induced by ouabain. The results indicate that the effects of neferine on APD and Vmax seem not to be related to the frequency of stimuli, and its anti-arrhythmic action is relevant to the inhibitory effects on Na+, K+, Ca2+ currents of myocardium.

Action Potentials↗
PubMed1989

[Effects of neferine on transmembrane potential in rabbit sinoatrial nodes and clusters of cultured myocardial cells from neonatal rats].

Neferine (Nef), a bis-benzylisoquinoline alkaloid first isolated from the seed embryo of Nelumbo nucifera G in China, possesses an anti-arrhythmic action. The effects of Nef on the transmembrane potential were studied in rabbit sinoatrial nodes and the clusters of cultured cardiac myocytes from neonatal rats. Nef 30 mumol/L suppressed the amplitude of action potential (APA) from 57 +/- 5 to 42 +/- 4 mV, and the maximal upstroke velocity (Vmax) from 1.7 +/- 0.3 to 0.9 +/- 0.4 V/s (n = 5, P less than 0.0) in rabbit sinoatrial nodes. Nef (40 mumol/L) decreased the APA from 92 +/- 8 mV of control to 80 +/- 4 mV, and Vmax from 20 +/- 5 to 12 +/- 4 V/s (P less than 0.01) in the clusters of cultured cardiac myocytes from neonatal rats. The effects on APA and Vmax were concentration-dependent. The results indicate that Nef has an inhibitory effect on the slow transmembrane Na+ and/or Ca2+ current of myocardium.

Alkaloids↗
PubMed1989

[A study of acute toxicity of mitoxantrone].

Acute toxicity of mitoxantrone (DHAQ) synthetized by Department of Organic Chemistry, School of Pharmacy, WCUMS was studied in mice and dogs. The toxic effects were compared with those of adriamycin (ADR). The LD50 were 6.6 +/- 1.3 and 7.1 +/- 1.6 mg/kg DHAQ, 7.9 +/- 2.1 and 10.7 +/- 2.2 mg/kg ADR (P = 0.95) respectively on observation with a single dose i.v. and i.p., for 21 days in Kunming mice. The toxicity appeared to be delayed with DHAQ and ADR. The earliest death occurred on 4th day after treatment in mice. In the third week still a few died. There were obvious decreases in WBC counts in the peripheral blood of mice receiving either 1-2.5 mg/kg DHAQ or 2.5-5 mg/kg ADR with a single dose i.p.. The WBC count could return to normality after 3 weeks with the withdrawal of the drugs. On electron microscopic examination of myocardial samples from mice 4 days after a single dose of 20 mg/kg DHAQ i.p., mitochondria swelling and vacuoles formation in some cells were shown. Besides the above-mentioned changes, some myocytes exhibited disorientation and loss of myofilaments in the mice which received equivalent dose of ADR. In dogs anaesthetized a temporary falling of blood pressure and slowing of heart rate were observed following 5-10 mg/kg DHAQ i.p.. When a dose of 50-100 mg/kg was given, the blood pressure dropped continuously until death.

Animals↗
PubMed1989

[Light and electron microscopic observations on endodermal sinus tumor of the ovary].

The results of light and electron microscopic studies of the endodermal sinus tumor of ovary are presented. Although histologic features of the tumors appeared to be much varied, ultrastructurally all tumor cell seemed to show changes essentially of the same nature. The histogenesis of endodermal sinus tumor production of AFP by the hyaline globule and the basement membrane-like substance present only in this type of tumor, are discussed. The results of the present study support the view that the tumor originate from the embryonal yolk sac cells.

Adolescent↗