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Biomedical subjects

F Franconi

Publications and source records attributed to F Franconi.

At least 91 records · Page 5Linked to original sources

The effects of taurine on pharmacologically induced myotonia.

Taurine reduces the excitability of striated muscle fibers by increasing the membrane conductance to chloride ions (GCl). This action was tested on rats made myotonic by drugs that block GCl by different mechanisms. Experiments were made "in vivo" using electromyographic (EMG) recordings and "in vitro" with intracellular microelectrode recordings from extensor digitorum longus muscle fibers. Taurine did not antagonize the myotonic discharges produced in vivo by anthracene-9-carboxylic acid, nor did it restore GCl lowered in vitro by this agent. However, when myotonia was chronically induced by 20,25 diazacholesterol, taurine given chronically in vivo or acutely in vitro antagonized the EMG myotonia as well as the reduced GCl and increased excitability of single fibers. We conclude that taurine acts directly on chloride channels to modify their kinetics. Our findings suggest that further clinical studies on the use of taurine in muscle disease involving abnormal excitability or chloride channel function will be useful.

Animals↗

Effect of ICV taurine on the impairment of learning, convulsions and death caused by hypoxia.

The effect of the intracerebroventricular (ICV) administration of taurine on amnesia, convulsions and death caused by hypoxia was investigated in mice. Taurine in doses of 80-100 micrograms/mouse impaired acquisition of a single trial in passive avoidance performance, but protected mice from the learning impairment induced by hypoxia. Neither beta-alanine nor saccharose were able to mimic the effects of taurine. Taurine had no effect on amnesia induced by scopolamine injected intraperitoneally. Taurine protected against the onset of convulsions induced by hypoxia, while convulsions induced by pentylenetetrazole (PTZ) and hyperbaric oxygen were unaffected. The survival time of mice exposed to hypoxia was significantly increased by taurine treatment. These data suggest that taurine may play a role as an antihypoxic agent.

Amnesia↗

Serum digoxin and beta-methyldigoxin in elderly patients on hospital admission: correlation with home compliance and clinical variables.

Serum digoxin and beta-methyldigoxin (BMD) were measured in 165 elderly patients (age greater than 60 years) admitted to hospital, of whom 109 had been treated at home with digoxin and 56 with BMD. The mean BMD level was significantly lower than that of digoxin (1.1 vs. 1.4 ng/ml). Creatinine clearance and daily dose were the variables most strongly associated with digoxin level, and the prescribed dose and serum albumin were the best predictors of the BMD concentration. Compliance was assessed by a compliance index (CI), namely the ratio of the measured glycoside concentration, corrected for creatinine clearance, over the expected steady-state dose, calculated from a hospitalized reference group. Compliant individuals in both treatment groups, i.e. those with a CI greater than the median value, were characterized by a lower daily dose and dosage frequency. Toxicity, whether clinical or electrocardiographic, was present in 9% of the patients and was associated only with a significantly higher mean serum level of the drug.

Aged↗

[3H]-nitrendipine binding in membranes obtained from hypoxic and reoxygenated heart.

We compared the binding properties of [3H]-nitrendipine in heart membranes from normal guinea-pig heart and from hypoxic or hypoxic and reoxygenated heart. The [3H]-nitrendipine binds a single class of high capacity (Bmax 667.2 +/- 105.2) with high affinity (KD 0.14 +/- 0.02) binding sites. By contrast, in membranes of hypoxic and reoxygenated heart the Bmax decreases significantly while it remains unaffected during hypoxia. Xanthinoxidase activity is increased in hypoxic-reoxygenated hearts.

Aerobiosis↗

The action of taurine on chloride conductance and excitability characteristics of rat striated muscle fibers.

Taurine and related compounds were applied to rat extensor digitorum longus muscle fibers in vitro, and the effects on membrane potential, cable parameters, component conductances and excitability were observed with microelectrodes. After 20 min in 60 mM taurine the fibers hyperpolarized and there were decreases in the latency of a rheobasic stimulus, the duration of the action potential and the maximum number of spikes elicited by depolarizing pulses. The effects of taurine on membrane resistance are attributed to a specific dose-dependent increase in membrane chloride conductance (G) with little or no effect on membrane potassium conductance. C1Gamma-aminobutyric acid at 30-60 mM also produced a specific increase in GC1 but, unlike taurine it caused a significant depolarization. beta-alanine or sucrose at 60 mM did not mimic any of the effects observed with taurine at this concentration. It was concluded that the actions of taurine and GABA on excitability can be explained by increases in GC1.

Alanine↗

L-arginine methylester reduces Ca2+/Cl(-)-dependent L-[3H]glutamate binding and Ca2+-activated neutral protease activity in rat hippocampal membranes.

Specific binding of L-[3H]glutamate was measured in Tris-HCl buffer in rat hippocampal membranes. In these experimental conditions 1 mM CaCl2 induced an increase in binding due to an increase in Bmax. L-Arginine methylester did not modify the Cl(-)-dependent binding of L-[3H]glutamate, but it decreased Ca2+/Cl(-)-stimulated binding in a dose-dependent manner, decreasing Bmax without changing KD. L-Arginine methylester reduced calcium-activated neutral protease activity in a dose-dependent manner. Serine protease inhibitors (aprotinin and di-isopropylfluorophosphate) did not affect L-[3H]glutamate binding, whereas leupeptin reduced it in a dose-dependent manner. L-Arginine did not mimic the effect of L-arginine methylester in either model.

Animals↗

The effects of the calcium channel agonist, Bay K-8644, on guinea-pig ileum and rat uterine horn.

Bay K-8644 (methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2- trifluoromethylphenyl)pyridine-5-carboxylate) concentration-dependently caused contractions of the partly depolarized ileum, but at higher concentrations (10(-6) to 10(-5) M) produced relaxation. 10(-8) to 4 X 10(-7) M nifedipine antagonized while 10(-9) and 4 X 10(-9) M potentiated Bay K-8644. On the partly depolarized uterus, Bay K-8644 (10(-9) to 10(-6) M) had only a spasmogenic effect whereas nifedipine (4 X 10(-9) to 10(-7) M) was spasmolytic. Verapamil and diltiazem (each at 10(-4) M) both reduced the maximal response to Bay K-8644, while other spasmolytics were ineffective. Thus, Bay K-8644 activates ileum and uterus by opening voltage-operated Ca2+ channels, but its relaxant action at high concentration and its potentiation by nifedipine is not seen in both organs. Such differences probably depend on the concentration of the compounds used and the polarization state of the cell membranes.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Positive inotropic effect of some taurine-related compounds on guinea-pig ventricular strips perfused with low calcium medium.

Taurine exerts a positive inotropic effect at a low calcium concentration. Of the compounds chemically related to taurine only L-cysteic and 2-aminobenzenesulfonic acid mimic taurine action. Their effect is concentration-dependent and not linked to the restoration of taurine tissue concentration in guinea-pig ventricular strips. Our data demonstrate that: (1) carbon chain length between amino and sulfonic groups is a crucial factor in the development of activity. (2) Substitution of the sulfonic group with other acid functions such as the substitution of the primary amino group or the introduction of the -COOH group onto the beta-carbon brings about a lack of activity.

Animals↗

Effect of sodium selenite on guinea-pig cardiac isolated mitochondria.

The pre-incubation with sodium selenite reduces the respiratory index in guinea-pig cardiac mitochondria when alpha-ketoglutarate and glutamate are used as substrates. This decrease is dose-dependent. On the other hand, no modification in respiratory index is measured with malate or malate plus pyruvate. The effect on sodium selenite is prevented by CoA administration. Moreover, 25 microM sodium selenite reduces the Km and Vmax of alpha-ketoglutarate dehydrogenase measured at steady-state with variable amount of CoA.

Animals↗

Liver function following hypovolemic hypotension in rats anaesthetized with halothane or enflurane.

Rats which had approximately 25-30% of their calculated blood volume removed were exposed to halothane (1%) or enflurane (2%) in 33% oxygen for 30 min. Hepatic function was evaluated by determining, at various time intervals, serum activities of glutamic-oxalacetic and glutamic-pyruvic transaminase, acid phosphatase and gamma-glutamyl-transpeptidase. In this model serum enzyme activities and animal mortality were significantly increased when hypovolemic hypotension was induced during halothane anaesthesia. The same events did not occur in bleeding animals anaesthetized with enflurane. The marked disparity in hepatic dysfunction and mortality between halothane and enflurane-anaesthetized rats during hypovolemic hypotension may be explained by the more pronounced decrease of oxygen available for the liver and production of reductive toxic intermediates in animals exposed to halothane.

Anesthesia↗

Functional and binding evidence of taurine inhibition of alpha-adrenoceptor effects on guinea-pig ventricle.

The effect of taurine on alpha- and beta-mediated positive inotropic effects was investigated in guinea-pig ventricular strips. Loading with taurine dose-dependently antagonized the phenylephrine-induced positive inotropic effect while it was ineffective on beta-mediated positive inotropic effect. The superfusion with a taurine-free medium determined a loss of intracellular taurine, while the loading with 20 mM taurine prevented this depletion. Preincubation of cardiac membranes with different concentrations of taurine (1 to 20 mM) decreased 3H-prazosin binding, and the saturation curve obtained after preincubation of cardiac membranes with 20 mM taurine showed that taurine had a more marked effect on the number of binding sites. In both experimental models, beta-alanine did not mimic any taurine effects, suggesting that taurine actions might be specific.

Animals↗