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Biomedical subjects

F Tanzi

Publications and source records attributed to F Tanzi.

13 recordsLinked to original sources

[Cardiac interactions between ketanserin and the calcium antagonist nifedipine].

Ketanserin and calcium antagonists are frequently used for the treatment of arterial hypertension in the elderly. The possibility that combined treatment with ketanserin and the calcium antagonist nifedipine have a pro-arrhythmic effect was investigated in 20 normal volunteers aged > 60 years with normal or slightly elevated blood pressure. Each subject received monotherapy with ketanserin or nifedipine for 1 week and the combined treatment during the following week. Clinical and biochemical parameters, ECG and 24-hour ECG recording were monitored before and at the end of the first and second treatment weeks. Ketanserin and nifedipine given in monotherapy or in combination did not modify, on average, blood pressure, heart rate, the biochemical variables and the QT interval. In the 24-hour ECG recordings, 2 normal subjects developed a marked increase in the frequency of ventricular ectopics, couplets and ventricular tachycardia after combined treatment. Therefore, the present investigation does not exclude the possibility that combined treatment with ketanserin and nifedipine could increase the prevalence of arrhythmia in some elderly patients.

Aged

Voltage-gated Ca entry in isolated bovine capillary endothelial cells: evidence of a new type of BAY K 8644-sensitive channel.

Isolated bovine capillary endothelial cells have been examined for voltage-dependent Ca entry. All cells displayed a low threshold activity, with the main characteristics of a T-type transient current, when examined using whole-cell recording for activation and inactivation and cell-attached conditions or inside-out patches for the elementary conductance (8 pS). 25% of the cells displayed an additional sustained current in 5 mM CaCl2 above -40 mV, which was enhanced by application of BAY K 8644, but almost insensitive to superfusion with nicardipine. Two types of channels (2.8 and 21 pS, in 110 mM BaCl2) were shown to have a BAY K 8644 sensitivity. The large conductance channels were L-type channels. The smaller events were elicited at more hyperpolarized potentials (by some 30 mV). Their mean open time was 16 ms in control conditions. In presence of BAY K 8644, additional long open times were observed (up to 100 ms as compared to 7.8 ms for the time constants of the slow mode of the L-type channel). We refer to these channels as SB channels: of small conductance and sensitive to BAY K 8644. In the presence of nicardipine, SB channels are not noticeably modified, in contrast to the L-type openings which are abolished. Also, SB open times are close to control values when nicardipine is added after a BAY K 8644 application. We suggest that, at physiological concentrations of divalent ions, an SB-type activity is elicited above -40 mV which generates the low threshold sustained current.

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

Calcium-activated potassium channels in native endothelial cells from rabbit aorta: conductance, Ca2+ sensitivity and block.

1. Isolated native endothelial cells, obtained by treatment of rabbit aortic endothelium with papain and dithiothreitol, were voltage clamped, and single channel (unitary) and spontaneous transient outward currents (STOCs) were recorded from both whole cells and excised membrane patches. 2. In inside-out patches, the reversal potential of unitary currents was dependent on the extracellular K+ concentration and had a single-channel slope conductance of 220 pS in symmetrical 140 mM-K+ solutions. The open-state probability (Po) of the unitary K+ currents was sensitive to the intracellular Ca2+ concentration with half-maximal activation at approximately 1 microM at +20 mV. The ionic selectivity and Ca2+ sensitivity indicate that a large conductance, Ca(2+)-activated K+ channel is present in freshly dissociated rabbit aortic endothelial cells. 3. The frequency and amplitude of whole-cell unitary currents and amplitude of spontaneous transient outward currents were voltage-dependent. Whole-cell outward K+ currents evoked by depolarizing voltage ramps had amplitudes often corresponding to the simultaneous opening of more than five single Ca(2+)-activated K+ channels. Lowering the intracellular EGTA concentration tenfold, and hence the Ca2+ buffering capacity of the cell, increased unitary K+ current activity and shifted the relationship between Po and membrane potential by approximately -20 mV. 4. Bradykinin (1 microM), adenosine 5'-triphosphate (3 microM) and acetylcholine (3 microM) applied extracellularly evoked a biphasic increase in N Po (where N is number of channels activated) of the Ca(2+)-activated K+ channel studied in the whole-cell recording configuration. The development of a biphasic response to agonist stimulation requires a source of extracellular Ca2+. The sustained increase in N Po of the Ca(2+)-activated K+ channel was attenuated upon the removal of external Ca2+ (Mg2+ replacement) or in the presence of the Ca2+ entry blocker, Ni2+, and the potassium channel blockers tetrabutylammonium (TBA) or tetraethylammonium (TEA). 5. Unitary and spontaneous transient outward currents were inhibited by extracellularly applied TEA (0.5 mM), TBA (0.5-5 mM) and charybdotoxin (100 nM). Ca(2+)-activated K+ currents were blocked completely by 5 mM-TEA, whereas 3,4-diaminopyridine (1 mM), Ba2+ (10 mM) and apamin (0.1-1 microM) did not abolish these K+ currents. 6. The K+ channel opener cromakalim (10 microM) evoked a sustained increase in N Po of the Ca(2+)-activated K+ channels which was not potentiated by the addition of bradykinin. Glibenclamide (10 microM) alone increased N Po and partially inhibited the cromakalim-induced increase in N Po with respect to control.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine

[Falls of elderly people--a systematic evaluation is necessary].

Falls of the elderly represent a real challenge for both the physician who is called in order to evaluate the causes and consequences of a trauma and the patient who is menaced in his physical and mental integrity. But falls question also the family who feels insecure and guilty as well as society, which sees itself confronted with the rising cost induced by the request of services and institutions. Only a systematic approach, considering factors of surroundings, will allow us an exhaustive evaluation of each individual patient and will, on the other hand, enable us to foresee, beyond the introduction of therapy, preventive measures. In the present article a proposal is made for a predominantly clinical evaluation in the perspective of general health promotion. In this way a fall can also become an occasion for the patient to rethink in a useful way the necessary reorganization of his own life, which in the course of years is dominated more and more by the aspiration for security.

Accidental Falls

Voltage-dependent transient calcium currents in freshly dissociated capillary endothelial cells.

Dissociated capillary endothelial cells display a voltage-dependent Ca current activating around the resting potential. The initial transient component of the current corresponds to a Ca channel of the T type. Some cells also display a plateau component corresponding to a distinct dihydropyridine-sensitive Ca channel. Depolarization induced by high external K+ elicits an increase in cytoplasmic Ca concentration. Confluent cells have been found to express the same Ca permeabilities.

Adrenal Medulla

Calcium-dependent chloride transient currents in the immature oocyte of the frog, Rana esculenta.

Transient currents of chloride were studied in the plasma membrane of immature frog oocyte in voltage clamp conditions. The transients appeared to be activated by an influx of Ca2+ from the external medium. The mechanism leading to a surge of intracellular Ca2+ concentration needed at least 30 sec before full recovery. It was inhibited by substituting Ba2+ for Ca2+ in the external medium, or in the presence of La3+, Co2+ and Cd2+, or when external Na+ was replaced by Li+. Verapamil proved ineffective. The data suggest that an intracellular system of Ca-activated Ca-release is present in the frog oocyte, which can be primarily activated by membrane hyperpolarization via an influx of Ca2+ through non-selective channels.

Animals

[Systemic thrombolysis using streptokinase. Experiences at the Civic Hospital of Lugano in the framework of the ISIS-2 study].

With a small group of Swiss hospitals we had an opportunity of participating in ISIS-2, the major study on thrombolysis in acute myocardial infarction. Experience with our microcosm (Ospedale Civico Lugano) was compared with the macrocosm of the results of ISIS-2 in 17,187 randomized patients (in brackets). Mortality was 5.1% (7.8%) in our streptokinase group and 15.8% (12.8%) in our placebo group. In the ISIS-2 study the combination of thrombolytic therapy with streptokinase, and of antiplatelet therapy with aspirin, showed a reduction of approximately one third in acute mortality of myocardial infarction, stroke and reinfarction. Our experience confirms the reduced incidence of allergic side effects (3.5%), major bleeding (0.3%) and minor bleeding (2.9%) during or after thrombolytic therapy.

Administration, Oral

Influence of thyroid state on mechanical restitution of rat myocardium.

The purpose of this study was to determine whether thyroid state affects the beat-to-beat regulation of contractile strength in cardiac muscle. Transmembrane action potential and isometric force were simultaneously recorded in right ventricular papillary muscles from euthyroid, hypothyroid, and hyperthyroid rats. Large thyroid state-dependent alterations in the contractile response of the muscles were not accompanied by any significant difference in the action potential. During steady-state stimulation, single test stimuli were interpolated at varying intervals. Action potential duration and peak force of the test responses were plotted against the test stimulus interval to produce electrical and mechanical restitution curves. In all muscles studied, electrical and mechanical restitution followed different time courses; over a wide range of test intervals, action potential duration and peak force of the test responses changed in opposite directions. Thyroid state profoundly affected the recovery of contractile strength, while only minor differences were found among the electrical restitution curves of the three groups of preparations. Mechanical recovery was much faster in hyperthyroid and slower in hypothyroid than in euthyroid muscles. We conclude that electrical and mechanical restitutions occur through separate processes and that the thyroid state affects only the mechanisms responsible for the contractile recovery of rat myocardium. The modifications induced by thyroid dysfunction on contractile recovery might be accounted for by an effect of thyroid state on a time-dependent recycling of calcium by the sarcoplasmic reticulum.

Action Potentials

Acetylcholine-induced currents at plasma membrane of the frog oocyte.

Although with remarkable variability, membrane permeability in Rana oocytes can be modified by application of acetylcholine. The experiments were carried out in voltage-clamp conditions. Like in Xenopus, the responses proved to be related to activation of muscarinic receptors operating membrane channels probably selective for Cl-. At differences with Xenopus, the net acetylcholine-induced current showed remarkable deviation from linearity, displaying outward-going rectification. Application of acetylcholine typically produced opening of membrane channels, while in late spring, we observed the opposite effect in several batches of oocytes.

Acetylcholine

In vitro action of uridine diphosphate glucose (UDPG) on phrenic diaphragm preparations.

The action of uridine-5'-diphosphoglucose (UDPG) on the contractile response of the phrenic diaphragm preparation from guinea pig was investigated. UDPG activity was assayed on the preparation at rest or during the exercise; in this case indirect electrical stimulation of phrenic diaphragm preparation or direct stimulation of denervated or curarized muscle were employed. Krebs' solutions adequately modified with regard to glucose concentration were used. The effect of UDPG on the neuromuscular junction was also investigated by recording miniature end plate potentials. An effect of the drug on neuromuscular transmission and on glucose metabolism could be demonstrated.

Action Potentials