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Biomedical subjects

T Li

Publications and source records attributed to T Li.

At least 577 records · Page 32Linked to original sources

The negative inotropic effect of calcium overload in cardiac Purkinje fibers.

The role of calcium in increasing or decreasing the force of contraction was studied in canine cardiac Purkinje fibers perfused in vitro under conditions known to alter cellular calcium. The following results were obtained: (1) increasing calcium load by perfusing a low Na solution increases contractile force in the presence of a low concentration of strophanthidin and decreases it in high strophanthidin; (2) decreasing calcium load by decreasing extracellular calcium leads to opposite effects; (3) the positive inotropic effect of low [Na]0 becomes negative in the presence of high [Ca]0; (4) high K decreases contractile force and reverses the negative inotropic effect of low Na in the presence of high strophanthidin; (5) a low Na-Ca solution increases initially the contractile force: high strophanthidin reverses the effect at normal K and exaggerates at high K, as apparently calcium overload is relieved by high K; (6) a low Na-Ca solution slowly removes calcium overload induced by high strophanthidin; (7) a low [Na]0 solution does not decrease force in the presence of high strophanthidin if extracellular calcium is also low; (8) the rebound increase in force is shifted to lower calcium concentrations after exposure to a low sodium solution with or without strophanthidin, as calcium overload becomes greater. It is concluded that in Purkinje fibers calcium overload induced by different means leads to a decrease in contractile force and that the force decline can be reversed by decreasing cellular calcium either during or after calcium overloading.

Animals↗

Calcium antagonist blockade of slow action potentials in cultured chick heart cells.

The effects of four Ca antagonists, bepridil, diltiazem, nifedipine, and verapamil, on slow channels were studied in cultured cell reaggregates prepared from 14-day-old chick embryonic hearts. The cell membrane was partially depolarized to about -45 mV by using 22 mM KCl to inactivate the fast Na+ channels. Slow action potentials were induced by 10(-6) M isoproterenol with electrical stimulation. Cumulative dose-response curves for the effect of the four drugs on the blocking of slow action potentials (using Vmax as the indicator) were analyzed by Hill plots. The dose values for 50% of maximal effect, at a stimulation frequency of 60/min, were (in order of decreasing potencies) as follows: 5.2 X 10(-9) M for nifedipine, 3.1 X 10(-7) M for diltiazem, 1.2 X 10(-6) M for verapamil, and 5.1 X 10(-6) M for bepridil. The effect of all four Ca antagonists showed use (or frequency)-dependency, i.e., the drugs were more effective at higher stimulation rates. This may reflect a blocking action of the drugs on the nonresting states of the channels and (or) a slowing of the recovery kinetics of the channels from the inactivated state back to the resting state. In a separate type of experiment utilizing a 5-min rest period in the presence of the drugs, nifedipine blocked and bepridil exhibited some depression of the first action potential elicited, i.e., use-independent effect, indicating that these drugs may also act on resting channels. Thus, these four Ca antagonists have a prominent use-dependent component in their actions, and one or two may also have a use-independent component.

Action Potentials↗

Stimulation of slow action potentials in guinea pig papillary muscle cells by intracellular injection of cAMP, Gpp(NH)p, and cholera toxin.

To test the hypothesis that intracellular cAMP has a regulatory role in cardiac slow channel function, intracellular pressure injections of cAMP and adenylate cyclase activators, Gpp(NH)p and cholera toxin, were carried out. Guinea pig papillary muscles were depolarized to about -45 mV by superfusion with 22 mM K+-Tyrode's solution to inactivate the fast Na+ channels. Induction of slow action potentials or enhancement of ongoing slow action potentials was observed in about 70% of all cells in which a successful intracellular injection of the testing compounds was obtained. The slow AP is highly dependent on slow inward current and is known to be enhanced by catecholamines. The effect of the injected cyclic nucleotides and related compounds occurred within 3 minutes after starting the injection, whereas superfusion with these compounds (dibutyryl cAMP was used in place of cAMP) required 10-30 minutes to show an effect. This difference is attributed to the intracellular injection of the compound. The effect on stimulating slow action potentials persisted (greater than 5 minutes) after termination of the application of either Gpp(NH)p or cholera toxin, indicating the long-lasting nature of their action. The effect of the cAMP injections decayed within 1 minute. Intracellular injection of 5'-AMP was without effect. These results support the view that a causal relationship exists between intracellular cAMP level and slow channel function. Phosphorylation of a protein constituent of the slow channel by a cAMP-dependent protein kinase may be involved.

Action Potentials↗

[Mechanism of glycerol and methanol action on soluble ATPase of mitochondria].

The effects of methanol, butanol, glycerol, glucose, sucrose and inorganic anions on the activity of soluble ATPase from mouse liver mitochondria were studied. Glycerol inhibited, while methanol stimulated the enzyme activity uncompetitively with respect to ATP and competitively with respect to each other. Glycerol-induced inhibition of ATPase was competitive with respect to sulphite; methanol competed with thiocyanate for the enzyme activity. The Arrhenius plots for ATPase revealed bends at 20 degrees and 30 degrees C in the presence of sulphite, chlorine, thiocyanate, glycerol and methanol. It was assumed that all the compounds tested influenced soluble ATPase by changing the nucleophilic activity of H2O.

Adenosine Triphosphatases↗

Thermodynamic studies of polymerization of deoxygenated sickle cell hemoglobin.

Solubilities of deoxygenated sickle cell hemoglobin (deoxy-Hb S), at varying pH and temperature over a range of concentrations encompassing those found in erythrocytes, were measured. The technique involved ultracentrifugation, which gave values of the supernatant concentration and the mass of the sedimented material. The data establish that the solubility of doexy-Hb S is the saturation concentration and is independent of initial concentration. The mass of the pellet phase increases linearly with initial concentration. Moreover, the saturation concentration represents the critical concentration above which monomers are in equilibrium with polymers. These polymers are the putative cause of erythrocytes deformation associated with sickle cell anemia. The solubility-pH profiles of deoxy-Hb S at various temperatures, unlike those of other proteins, show no minima at the isoelectric pH but instead show a marked decrease in solubility below pH 7.0, indicating the predominance of polymerization over the expected increase in solubility. Deoxy-Hb S, within specified ranges of temperature and pH, possesses a negative temperature coefficient of solubility, a property characteristic of hydrophobic interactions. The saturation concentration is, however, temperature independent at conditions close to physiological. The enthalpy of polymerization (3.5 kcal/mol) is temperature independent from 6 degrees to 22 degrees for all pH values between 6.45 and 7.40. In the range of 22 degrees to 38 degrees, this parameter becomes less endothermic, having a value of 2.5 kcal/mol at pH 6.45 and a value of zero at pH 7.20. Such behavior of the system suggests a phase transition near 22 degreas. Within the range of conditions examined the polymerization is entropically driven.

Hemoglobin, Sickle↗

The purification of human urinary kallikrein with ion-exchange radial flow membrane chromatography.

A method was developed for the purification of kallikrein from human urine. The procedure consisted of three steps: ultradialysis, diethyl-(2-hydroxypropyl) aminoethyl (QAE) ion exchange radial flow membrane chromatography and affinity chromatography on aprotinin agarose. It is simple and suitable for large-scale purification. The purified product was checked by SDS-PAGE and matrix-assisted laser desorption:ionization mass spectrometery (MALDI). A single band with apparent molecular weight (MW) 42,000 in SDS-PAGE and a single monomer peak with MW33,000 in MALDI were observed, respectively. The biological activity tested by ELISA showed positive immunological identity of the purified product compared with human urinary kallikrein standard.

Amino Acid Sequence↗

Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of furosemide.

The pharmacokinetics and pharmacodynamics of furosemide were evaluated after intravenous administration of the same total dose of furosemide in different lengths of infusion time (10 s, 30 min, 2 h, and 8 h) to 6 dogs. The fluid loss in urine was immediately replaced volume for volume with intravenous infusion of Lactated Ringer's solution. The pharmacokinetic parameters such as per cent of the dose excreted in urine, total body and renal clearances, and terminal half-life were not significantly different with four different infusion times. The volume of distribution at steady state and mean residence time based on venous data, on the other hand, appeared to increase with increasing infusion time. The mean values for Vss were 0.334, 0.478, 0.499, and 0.708 1 kg-1 for 10 s, 30 min, 2 h, and 8 h of infusion, respectively, and the corresponding values for MRT were 17.5, 22.2, 24.8, and 38.1 min. The diuretic effects (urine output and urinary excretion of sodium) were generally found to increase with increasing infusion times; the total mean 24 h urine outputs were 1102, 1464, 2190, and 3470 ml for 10 s, 30 min, 2 h, and 8 h of infusion, respectively, and the corresponding values for sodium excretion were 170, 175, 272, and 440 mmol. Furosemide plasma concentrations and hourly urinary excretion rates of furosemide, sodium, and potassium during the apparent steady state (between 2 and 8 h) in the 8 h infusion study were fairly constant.

Animals↗