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L Botta

Publications and source records attributed to L Botta.

At least 37 records · Page 2Linked to original sources
PubMed1995

Mechanisms for sensory adaptation in frog vestibular organs.

The effects of external low-Ca, high-Mg solutions were tested both on frog isolated semicircular canals and on single cells isolated from these sensory organs. Our results showed that these media were able to cancel slow adaptation of the ampullar microphonic current in the whole organ and to abolish a Ca-dependent K current (IK(Ca)) in single hair cells, suggesting that IK(Ca) is involved in vestibular sensory adaptation.

Adaptation, Physiological↗
PubMed1993

Pharmacokinetics of an HIV-1 gp120-specific chimeric antibody in patients with HIV-1 disease.

The pharmacokinetics of mouse V/human C (gamma 1, kappa) chimeric monoclonal antibody CGP 47 439 specific for the principal neutralizing determinant of human immunodeficiency virus type 1 (HIV-1) was studied in patients with stage IV HIV-1 disease in an open-labeled phase I/IIA trial. Twelve male patients were enrolled and nine completed the study. Patients were divided into three groups according to the extent of CGP 47 439 to bind to gp120 from their viral isolates: undetectable for group 1, modestly reactive for group 2, and strongly reactive for group 3. A first dose of 1, 10, or 25 mg was administered by intravenous infusion to group 1, group 2 and group 3 patients, respectively. The patients then received seven doses of 50, 100, or 200 mg, respectively, every three weeks. CGP 47 439 serum concentrations were determined by an ELISA using monoclonal antibody AB19-4 specific for the idiotope of CGP 47 439. Half an hour after infusion only 25.5-36.1% of the administered antibody was found in the serum, reflecting its rapid distribution in the extravascular space and possibly binding to gp120 antigen in some of the patients. The terminal elimination half-life (T1/2) was 16.2 days in group 1 patients, 9.7 days in group 2 and in group 3 patients 7.5 days and 9.1 days. An antibody response to CGP 47 439 was not a factor in determining elimination rates, because only very low and transient responses were found in three patients. These results suggest that the reactivity of CGP 47 439 with HIV-1 gp120 contributed to its elimination in HIV-1 infected patients.

Adult↗
PubMed1993

Sensory adaptation in frog vestibular organs.

Adaptation, i.e., the decrease with time in sensory units' afferent discharge to a constant stimulus, appears to be a common feature of the receptors belonging to acoustico-lateralis system: However, the mechanisms underlying this process are still a matter of debate. The present experiments demonstrate that sensory adaptation to both mechanical and electrical stimuli can be nearly suppressed after perilymphatic ouabain administration. This clearly indicates that the K+ homeostatic mechanisms [Valli et al., (1990) J. Physiol. (London) 430, 585-594] which control the K+ concentration gradient at both ends of vestibular hair cells play a predominant role in this process. The possible importance of different K+-dependent mechanisms in hair cell adaptation is discussed.

Adaptation, Physiological↗
PubMed1992

Mouse/human chimeric anti-HIV-1 gp120 antibody to the principal neutralizing determinant: tolerability and pharmacokinetics in cynomolgus monkeys, Macaca fascicularis.

In preparing for testing a pharmaceutical grade preparation of chimeric (mouse/human) antibody CGP 47,439 in HIV-1 infected individuals, it was administered to Macaca fascicularis (cynomolgus) monkeys to study tolerability, immunogenicity and pharmacokinetics. Four groups of monkeys, three males and three females per group, received respectively four infusions of 0, 1.43, 4.3, and 14.3 mg of CGP 47,439/kg body weight at one-week intervals. The chimeric antibody induced no fever, was tolerated well throughout the 50-day observation period, elicited no tissue damage and no anti-antibody response. The pharmacokinetic profile was similar at all dose levels with a mean T1/2 alpha of 14.2 h (range 11.8-19.3 h) and a mean T1/2 beta of 172.6 h (range 137.2-220.5h). Following four successive antibody infusions serum concentrations of CGP 47,439 increased without reaching a steady state, and its measured concentrations were comparable to the simulated values. Collectively the study has provided safety and pharmacokinetic data that would allow human studies with this antibody in AIDS patients.

Animals↗
PubMed1992

Evidence for L-glutamate release in frog vestibular organs.

The present study was devised in order to ascertain whether L-glutamate (Glu) is the neurotransmitter at the primary afferent synapse in frog vestibular organs. To this end different groups of frog isolated semicircular canals were stimulated by means of solutions slightly enriched in K+ (5 mM K(+)-rich solutions are sufficient to produce a strong, long-lasting, transmitter release from the basal pole of sensory cells) both in normal conditions and after low-Ca(2+)-high-Mg2+ impairment of the synaptic transmission. The concentration of Glu in the surrounding medium, determined by means of a bioluminescence-enzymatic method, was evaluated in two different experimental conditions: a) when the canals (5 canals placed inside little net bags) were immersed in a 5 mM K(+)-stimulating solution; b) during the superfusion of the canals (25 canals placed into a little perfusion chamber) with a 5 mM K(+)-stimulating solution. The net bag experiments demonstrated that K(+)-rich solutions can provoke an outflow of Glu from canal organs only if the crista ampullaris is present and functioning. Glu fluctuations were in fact suppressed by employing canals deprived of the ampulla or after low-Ca2(+)-high-Mg2+ synaptic blockade. The superfusion experiments demonstrated that the time course of 5 mM K(+)-induced release of Glu from the sensory organ strictly parallels the time course of 5 mM K(+)-induced EPSPs and spike discharge in afferent axons. These results strongly support the hypothesis that Glu is, or is released with, the afferent transmitter in frog inner ear sensory organs.

Animals↗
PubMed1992

Streptomycin blocks the afferent synapse of the isolated semicircular canals of the frog.

This study aimed to define the acute electrophysiological effects of the perilymphatic perfusion of streptomycin in the sensory apparatus of the semicircular canals of the frog. The ampullary DC potential, the vestibular nerve multiunit discharge, the nerve DC potential and the unitary EPSP activity were recorded in isolated semicircular canals of the frog (Rana esculenta L). The results demonstrated that perilymphatic microperfusion of streptomycin (0.1, 0.3, 1 and 3 mM) reduced both resting and mechanically evoked afferent discharge, while the response of the hair cells remains unchanged. Intracellular recordings from single afferent axons showed that the reduction of the afferent discharge was mainly due to a reduction of the amplitude, but not the frequency, of the EPSPs. These results indicate that streptomycin, when applied in the fluid bathing the synaptic pole of the sensory cells, can act as an antagonist of the vestibular afferent transmitter at the postsynaptic level.

Afferent Pathways↗
PubMed1992

Effects of cromakalim (BRL 34915) on resting and evoked activity in frog semicircular canals.

The effects of endolymphatic administration of cromakalim and glibenclamide were tested in isolated semicircular canals of the frog. The actions of the drugs were evaluated by recording: (1) the transepithelial potential between the endolymphatic and the perilymphatic sides of the crista ampullaris; (2) the slow nerve potential from the ampullar nerve; (3) the action potential discharge in afferent ampullar nerve fibres; and (4) the perilympathatic potassium concentration in the fluid bathing the outer surface of the crista ampullaris. The above mentioned parameters were recorded both at rest and during mechanical stimulation of the sensory organ. The results demonstrated that the endolymphatic administration of cromakalim (10(-4) M) produced an increase in both ampullar receptor resting activity and in perilymphatic K+ resting levels. By contrast all the parameters related to the mechanically evoked responses were practically unaffected. Glibenclamide (10(-4) M) proved able to cancel or to prevent cromakalim effects. These data suggest that the membrane of the hair cells is endowed with K+ channels regulated by internal ATP whose activation is mainly involved in the processes sustaining ampullar receptors' resting firing rate.

Adenosine Triphosphate↗
PubMed1991

Effects of hydrostatic pressure on sensory discharge in frog semicircular canals.

The effects of endolymphatic and perilymphatic pressure changes on resting and mechanically evoked responses were studied in isolated posterior semicircular canals of the frog. The results demonstrated that ampullar receptors are extremely sensitive to hydrostatic pressure changes (0.25 mm H2O were sufficient to produce distinct changes), being inhibited by endolymphatic pressure increases and facilitated by perilymphatic ones. Intracellular recordings from single afferent axons showed that the effects of hydrostatic pressure result from a modified transmitter release from the synaptic pole of the hair cells. Unlike resting activity, mechanically evoked activity was always depressed in the presence of a hydrostatic pressure. This indicates that the sensitivity of ampullar receptors to mechanical stimuli, i.e. the gain of the conversion process, is maximal when no pressure is present between the inner and the outer fluid. The possible action of hydrostatic pressure on vestibular receptors is discussed.

Afferent Pathways↗
PubMed1990

Perilymphatic potassium changes and potassium homeostasis in isolated semicircular canals of the frog.

1. Endolymphatic and perilymphatic potassium concentrations were measured with K(+)-sensitive microelectrodes in isolated semicircular canals of the frog. K+ levels were evaluated both at rest and during sinusoidal stimulation (0.05 Hz) of the sensory organ. 2. Mechanical stimulation of hair cells was associated with sinusoidal changes (about 0.2 mM) in the perilymphatic K+ concentration. 3. Perilymphatic K(+)-fluctuations were modified neither by impairment of the synaptic transmission at cyto-neural junctions nor by chronic denervation of the crista ampullaris, thus indicating that K+ ions were actually released by hair cells. 4. Voltage-clamp experiments of the whole sensory organ showed that K+ flows across the crista ampullaris can vary from 3 X 10(11) molecules of K+ s-1 at rest up to about 15 X 10(11) molecules of K+ s-1 during mechanical stimuli. 5. Measurement of intra-ampullar K+ concentration demonstrated that the amount of K+ transported from the perilymph towards the endolymph can be rapidly altered by modifying its perilymphatic levels. This suggests that vestibular organs are endowed with K+ homeostatic mechanisms able to buffer in a very efficient way the concentration of K+ in both the fluids bathing the crista ampullaris. 6. The possible role of K+ homeostatic mechanisms in hair cell adaptation is discussed.

Action Potentials↗
PubMed1989

Lumbar sympathetic ganglia in man: an electrophysiological study in vitro.

A method has been developed for the removal, preservation and electrophysiological study 'in vitro' of sympathetic lumbar chains (L1-L3) from subjects undergoing lumbar ganglionectomy in the treatment of peripheral vascular diseases. Extracellular recordings from interganglionic trunks, and intracellular recordings from single sympathetic neurons, were performed. The extracellular experiments substantiated the concept, hitherto deduced from animal experiments, that the preganglionic fibres in the sympathetic lumbar chain are mainly of a descending nature. In fact, stimulation of the interganglionic trunk cranial to ganglia is always much more effective in driving ganglion neurons to fire than stimulation of the interganglionic trunk caudal to ganglia. The intracellular experiments produced a good definition of the main electrical characteristics of human sympathetic neurons. The results can be summarized as follows: the resting membrane potential ranged from 50 to 75 mV (63.4 +/- 9.2 mV; 21 neurons); action potential amplitude from 62 to 93 mV (74.3 +/- 8.1 mV; 27 neurons); membrane input resistance was 42.3 +/- 12.6 m omega (8 neurons) and total membrane capacitance 83.7 +/- 15.3 pF (8 neurons).

Action Potentials↗
PubMed1986

Functional organization of the peripheral efferent vestibular system in the frog.

The functional organization of the efferent vestibular system (EVS) was studied in the isolated frog labyrinth. To ascertain whether, besides the efferent branching fibres that innervate several end-organs, the EVS is also endowed with efferent non-branching axons which might control a given population of sensory units in each end-organ, the 8th nerve and one of its branchlets were electrically stimulated while recordings of the spontaneous activity arising from the different sensors were made by impaling single afferent axons in all the 8th nerve branchlets. The results demonstrated that the vast majority of the sensory units whose activity was modified by stimulating the whole 8th nerve was also affected by stimulating an 8th nerve branchlet. These findings therefore rule out the possibility that the EVS is endowed with projective fibres and strengthen the view that the EVS is a highly divergent system with collaterals arising from single parent axons that innervate several end-organs. These experiments have also shown that the percentage of sensory units which are actually controlled by the EVS varies amongst the different labyrinthine organs. It is maximal in the sacculus (ca. 90%), somewhat lower in canal organs (ca. 80%) and the utriculus (ca. 70%) and considerably lower in the lagena (ca. 50%). This EVS arrangement therefore might allow information arising from some organs to be modified more extensively than that from others.

Animals↗
PubMed1986

[The percutaneous absorption of diclofenac].

The percutaneous absorption of diclofenac diethylammonium 1.16% (w/w) in a combination of emulsion cream and gel (Voltaren Emulgel) and of diclofenac sodium 1% (w/w) in a cream formulation (Voltaren cream) was investigated in guinea-pig, rabbit and man. The percutaneous absorption of diclofenac sodium in guinea-pig was 3 to 6% of the dose when the cream formulation in doses of 320, 100 or 40 mg was applied on 10 cm2 of occluded skin and left in place for 6 h. The transdermal delivery of 14C-labelled diclofenac yielded plateau plasma concentrations of radiotracer from 1.5 h after application until removal of the residual cream. Subsequently the steady state drug depots in the skin and muscle tissue were depleted promptly. During daily administration the steady state levels in the muscle tissue in proximity to the application site were about 3 times higher than in distant muscle tissue. By topical application on knee joints of rabbits diclofenac penetrated into the patellar ligament, the adipose corpus and the synovial fluid. In man the percutaneous absorption was 6% of the dose when the Emulgel formulation was spread by 5 mg/cm2 and left for 12 h on non-occluded skin. The pattern of metabolites of diclofenac in human urine was the same after topical and oral administration. In man, upon daily topical administration of 3 times 2.5 g cream formulation (10 mg/cm2) the diclofenac steady state plasma levels were 20 to 40 nmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

[Pre- and post-synaptic activity of glutamate on preparations of the frog semicircular canal].

Glutamate (Glu) has at least two sites of action in the frog semicircular canal: the hair cell (presynaptic) and the primary afferent nerve fibres (postsynaptic). Glu's action on the hair cell results in an increased release of the natural transmitter which is responsible for a substantial increase in the frequency of firing in primary afferents. Glu produces a long-lasting depolarization in the afferent nerve fibres which does not by itself elicit any afferent discharge of impulses when the release of the natural transmitter is prevented. The difficulty of reconciling some of the observations made of the effects of Glu in semicircular canals with its presumed role as an afferent transmitter in this organ is discussed.

Animals↗
PubMed1985

[Effects of changes in K+ in the perilymphatic fluid on the activity of vestibular receptors in the frog].

The effect of rapid changes in K+ concentration (from 0 up to 5 mM) in the perilymphatic fluid was tested on ampullar receptor activity in isolated semicircular canals of the frog. The effects of the different K-concentrations were evaluated by recording both the transepithelium potentials (Adc) and the postsynaptic potentials (EPSPs and spikes discharge) led off from the ampullar nerve. The results have clearly demonstrated that crista ampullaris sensory cells are extremely sensitive to K-changes (+/- 0.25 mM). In fact both transepithelial potentials and discharge activity (EPSPs and propagated spikes) of first order vestibular neurones may be decreased or increased by decreasing or increasing the K-concentration in the outer fluid. The possible mechanism of action of K+ on ampullar receptors is discussed.

Animals↗
PubMed1985

The effect of glutamate on the frog semicircular canal.

L-glutamate (Glu) has at least two sites of action in the frog semicircular canal: the hair cell (presynaptic) and the primary afferent nerve fibres (postsynaptic). Glu's action on the hair cell results in an increased release of the natural transmitter which is responsible for a substantial increase in the frequency of firing in primary afferents. The presynaptic action of Glu is antagonized by D-alpha-aminoadipate (D alpha AA). Glu produces a long-lasting depolarization on the afferent nerve fibres which does not by itself elicit any afferent discharge of impulses when the release of the natural transmitter is prevented. Glu-induced nerve depolarization is only partially antagonized by D alpha AA. The difficulty of reconciling some of the observations made of the effects of Glu in semicircular canals with its presumed role as an afferent transmitter in this organ is discussed, but this role is not definitely rejected.

2-Aminoadipic Acid↗