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Biomedical subjects

E Stefani

Publications and source records attributed to E Stefani.

198 records · Page 11Linked to original sources

Miniature potentials in denervated slow muscle fibres of the frog.

1. Pyriformis and iliofibularis muscles of the frog were studied with micro-electrodes. Both muscles contain a mixture of fast and slow muscle fibres, which can be distinguished by differences in their miniature end-plate potentials (min.e.p.p.s).2. In addition, the membrane time constant of fast fibres is < 20 msec, while that of slow fibres is > 200 msec.3. The characteristic difference in time constant persisted after denervation and allowed the identification of fibre type.4. Denervated slow fibres had min.e.p.p.s of variable time courses and skew amplitude distributions. Their frequency was lower than in normally innervated fibres, and could be increased by hypotonic solutions.5. In analogy with similar observations made previously in fast muscle fibres, it is suggested that after nerve degeneration the Schwann cells of small motor nerve fibres release packages of transmitter which give rise to min.e.p.p.s.

Acetylcholine↗

Resting potential and electrical properties of frog slow muscle fibres. Effect of different external solutions.

1. The electrical properties of frog slow muscle fibres were investigated with intracellular micropipettes to determine their characteristic length (lambda), specific membrane resistance (R(m)) and specific membrane capacitance.2. The value of lambda was about 1 cm in fibres of 1.2 cm length. The ;short cable model' was used to calculate R(m). Its mean value was 1.12 x 10(5) ohm cm(2), about 10-20 times larger than the value for twitch fibres. The mean value for C(m) was 3.24 x 10(-6) F/cm(2).3. Resting potentials measured immediately after penetration with a single micropipette were about - 80 mV. Lower values can be attributed to the effects of damage or leakage produced by micropipette insertion.4. Changes in external K concentration produced changes in the initially recorded resting potentials which follow the constant field theory using a ratio of Na: K permeabilities P(Na)/P(K) = 0.02. Changes in external Cl concentration produced little or no change in the resting potential or membrane resistance, indicating a low Cl permeability.5. In agreement with previous work, slow fibres showed a time-dependent decrease in resistance (;delayed rectification') for membrane potentials more positive than - 60 mV. ;Anomalous rectification' observed in twitch fibres was not seen in slow fibres. In high external K concentrations the resistance of slow fibres is almost unaffected by changes in membrane potential.6. Increasing the concentration of external Ca (up to isotonic) has two distinct effects on slow fibres. It increases R(m) up to ten times, and it improves the stability of trans-membrane recordings, probably by reducing the leakage due to micropipette penetrations. Magnesium does not appear to have either of these effects.

Animals↗

Ionic mechanisms of cholinergic excitation in molluscan neurons.

Acetylcholine appears to be an excitatory transmitter at synapses on two different types of molluscan nerve cells: the so-called D- and CILDA neurons. The action of this substance is different in the two cases. In D-neurons, this compound increases the permeability of the subsynaptic or somatic membrane to chloride ions, and through a net efflux of this anion, depolarizes the cell. In CILDA neurons, on the other hand, acetylcholine depolarzies the cell by increasing its permeability to sodium ions.

Acetylcholine↗

Two different ionic mechanisms generating the spike "positive" afterpotential in molluscan neurons.

The ionic bases of the "positive" afterpotential (ap) have been examined in the so-called DInhi neurons of the central nervous system of Cryptomphallus aspersa. In these cells E(K) has been determined and its value compared with the equilibrium, potential of the ap (E(ap)). It has been found that in half of the studied cells the E(K) value is very close to E(ap) whereas in another half, the difference (E(K) - E(ap)) is large and amounts to circa -10 mv. The effects of changes in the concentration gradients of K(+), Cl(-), and Na(+) were assayed in both groups of cells. When the [K(i)/[K](o) ratio is reduced in both groups of neurons, the ap amplitude and the E(ap) diminished. In cells displaying a large (E(K) - E(ap)), Cl-free Ringer's solution diminished the ap amplitude and E(ap), but produced no effect in the neurons with a reduced (E(K) - E(ap)). A similar effect was observed if [Cl], was increased by intracellular injection of NaCl. Changes in both [Na](o) and [Na](i) were ineffective. It is concluded that K(+) is the only ion involved in the origin of the ap in the groups of cells with a low value for (E(K) - E(ap)). On the contrary, the ap of the neurons presenting large (E(K) - E(ap)) is produced by a simultaneous increase in the fluxes of both K(+) and Cl(-).

Action Potentials↗

An electrophysiological study of 5-hydroxytryptamine receptors of neurones in the molluscan nervous system.

1. 5-Hydroxytryptamine (5-HT) has been iontophoretically applied to the membrane of central neurones of Cryptomphallus aspersa; CILDA neurones (cells with inhibition of long duration) (Gerschenfeld & Tauc, 1964) are the only cells sensitive to 5-HT. The responses to 5-HT is always a depolarization. The CILDA cells studied were also depolarized by ACh.2. From experiments in which pulses of 5-HT and ACh were applied from a double-barrelled micropipette to the CILDA cell soma, it has been calculated that 5-HT and ACh receptors were located at different distances from the injecting micropipette tip. It has also been calculated from the diffusion equation that in the same CILDA cell a 5-HT concentration of 8.2 x 10(-9)M and a ACh concentration of 1.3 x 10(-8)M caused a similar peak depolarization.3. CILDA neurones show ;anomalous' rectification. 5-HT increases the membrane conductance of CILDA.4. 5-HT receptors of CILDA neurone are desensitized by repeated application of 5-HT. The desensitization lasts for ca. 40 sec.5. 5-HT receptors are blocked by lysergic acid diethylamide and its derivatives. Morphine chlorhydrate blocks them non-competitively.6. Some inhibitors of monoamine oxidase (trancylpromine, isocarboxazide, iproniazide and nialamide) have been tested. They do not prolong the action of 5-HT, but block the 5-HT receptors.7. No crossed desensitization between 5-HT and ACh has been observed. Atropine blocks both ACh-receptors and 5-HT receptors, 5-HT receptors appear to be blocked to a greater extent.8. The data presented support the assumption of a excitatory transmitter role of 5-HT to CILDA neurones, but further evidence is necessary to confirm this hypothesis.

Acetylcholine↗

Long-term and preventive effects of sublingual allergen-specific immunotherapy: a retrospective, multicentric study.

There is now an increasing body of evidence to support the practice of allergen-specific sublingual-swallow immunotherapy (SLIT) in the treatment of IgE-mediated respiratory allergies. Recent studies on traditional injection therapy have pointed out that this form of treatment is not only capable to decrease actual allergic symptoms, but may also have long-term clinical and preventive effects and may influence atopy natural history. In the year 2000, our group published a retrospective, multicenter study showing the efficacy and safety of SLIT in a survey of 302 patients. We now carried out a second study on the same patients, with the aim of investigating long-term and preventive effects of SLIT. Beside the well-known safety and efficacy of this treatment (80.8% of patients reported clinical benefits), SLIT proved also to elicit long term clinical effects: over a mean follow-up of 11.6 months after the end of treatment, 80.8% of patients still maintained the previously achieved benefits. During the follow-up period, only 1% of non-asthma patients reported an onset of respiratory symptoms, and only 9.6% of patients undergoing new skin tests showed new sensitizations. All the clinical benefits were strongly linked to the length of treatment: patients with long-lasting benefits were treated for a mean length of 29.1 months, while patients showing a return to pre-SLIT condition were treated for a mean 13.3 months. SLIT can obtain long-term and preventive effects so far attributed to injection immunotherapy.

Administration, Sublingual↗

Safety and efficacy evaluation of sublingual allergen-specific immunotherapy a retrospective, multicenter study.

In recent years, several controlled studies have proved the efficacy and safety of sublingual specific immunotherapy, as a possible alternative to the classic subcutaneous route of administration. This alternative option has been officially confirmed by the recent WHO position paper "Allergen Immunotherapy: Therapeutic Vaccines for Allergic Diseases'". Since sublingual immunotherapy has now been widely used for years, we carried out an open, multicentric, retrospective study to investigate the efficacy and safety of this form of treatment in a large number of patients. To this end, we studied 302 subjects undergoing sublingual immunotherapy for at least three months with different allergen compositions. Notwithstanding the obvious limitations due to the study design, this survey has confirmed the high efficacy and safety of this form of treatment, as already reported in previous controlled studies. Sublingual immunotherapy appears to be a simple, well-tolerated and effective method of treatment of allergen-specific diseases.

Journal Article↗

Increased intracellular calcium triggered by immune mechanisms in amyotrophic lateral sclerosis.

Although the causes of motor neuron degeneration and death in amyotrophic lateral sclerosis (ALS) is unknown, recent evidence suggests a prominent role for increased intracellular calcium, possibly triggered by autoimmune mechanisms. The presence in ALS patients of paraproteinemias, lymphomas, lymphoid cells in the central nervous system (CNS) and the availability of animal models of immune-mediated motor neuron disease provide circumstantial evidence for autoimmunity. Direct evidence derives from the demonstration that ALS IgGs bind to voltage-gated calcium channels in 75% of sporadic cases, but not in familial ALS cases, and that ALS IgGs increase N-type and P-type calcium currents in neuronal cells and in lipid bilayers. These same ALS IgGs are cytotoxic for a motor neuron cell line (VSC 4.1) in vitro. In addition, following passive transfer to mice in vivo, ALS IgGs produce ultrastructural and calcium changes in synaptic vesicles and mitochondria of motor axon terminals, as well as in rough endoplasmic reticulum and Golgi complex of motor neuron perikarya, but not in sensory neurons or Purkinje cells. The reason for the selective vulnerability of motor neurons is not clearly defined, but a prominent possibility is the physiological absence in motor neurons of the calcium-binding proteins calbindin-D28k and parvalbumin. These studies emphasize the central role of increased intracellular calcium in motor neuron cell death in sporadic ALS, and the role of autoimmunity in triggering such increases.

Amyotrophic Lateral Sclerosis↗