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Biomedical subjects

A Ferraresi

Publications and source records attributed to A Ferraresi.

At least 19 recordsLinked to original sources
PubMed2006

Vascular endothelial growth factor (VEGF) expression in noise-induced hearing loss.

Noise-induced hearing loss has been associated with alterations in cochlear blood flow. Our study analyzed the expression of Vascular Endothelial Growth Factor (VEGF) and its functional receptors, Flt-1 and Flk-1, in the cochlear structures of noise-exposed and unexposed guinea pigs. VEGF is a prototypical angiogenic agent, with multiple functions on vascular biology, ranging from vascular permeability to endothelial cell migration, proliferation, differentiation, and survival. Acoustic trauma was induced by a continuous pure tone of 6 kHz, at 120 dB SPL for 30 min. Auditory function was evaluated by electrocochleographic recordings at 2-20 kHz for 7 days. Noise-induced cochlear morphological changes were studied by immunohistochemistry and scanning electron microscopy. The expression of VEGF and its receptors was examined by immunohistochemistry and western blotting analysis. The hearing threshold shift reached a level of 60 dB SPL on day 1 after trauma and underwent a partial recovery over time, reaching a value of about 20 dB SPL on day 7. Outer hair cell loss was more prominent in the area located 14-16 mm from the apex. Increased cochlear VEGF expression was observed in noise-exposed animals, in particular at the level of stria vascularis, spiral ligament, and spiral ganglion cells. No changes were observed in the expression of VEGF-receptors. Our data suggest a role for VEGF in the regulation of the vascular network in the inner ear after acoustic trauma and during auditory recovery, with potentially important clinical and therapeutic implications.

Action Potentials↗
PubMed2004

Protective effects of alpha-tocopherol and tiopronin against cisplatin-induced ototoxicity.

OBJECTIVE: To investigate the possible protective effects of alpha-tocopherol and tiopronin against cisplatin-induced cochlear damage. Cisplatin ototoxicity and nephrotoxicity seem to result from the inhibition of cochlear antioxidant defences, causing an increase in the amount of reactive oxygen species. Antioxidants, such as alpha-tocopherol and tiopronin, are able to suppress lipid peroxidation, thus attenuating tissue damage. MATERIAL AND METHODS: Hartley albino guinea pigs were used. The animals were treated for 7 consecutive days with either (I) cisplatin alone, (II) cisplatin+alpha-tocopherol acetate, (III) cisplatin+tiopronin, (IV) cisplatin+alpha-tocopherol acetate+tiopronin, (V) alpha-tocopherol acetate alone or (VI) tiopronin alone. Changes in cochlear function were characterized by means of compound action potential threshold shifts. After the functional testing, tympanic bullae were removed and processed for morphological examination of the sensorineural epithelium. Renal function was evaluated by measuring serum blood urea nitrogen and creatinine levels. RESULTS: Cisplatin induced progressive high-frequency hearing loss of 40-50 dB SPL. Alpha-tocopherol and tiopronin co-therapy significantly slowed the progression of hearing loss. Treatment with alpha-tocopherol acetate or tiopronin alone was less effective. Morphological observations showed an important loss of outer hair cells and degeneration of the organ of Corti in the basal and middle turns. Injection of both alpha-tocopherol and tiopronin reduced cochlear outer hair cell loss more than treatment with a single drug. Beneficial effects of alpha-tocopherol and tiopronin on cisplatin-induced nephrotoxicity were observed. CONCLUSION: This study supports the hypothesis that alpha-tocopherol and tiopronin interfere with cisplatin-induced damage, and suggests that concurrent treatment with the two drugs can be useful in protecting against hearing loss.

Animals↗
PubMed2004

The role of antioxidants in protection from ototoxic drugs.

A number of studies have shown that cisplatin and gentamicin ototoxic effects may result from free radical-mediated damage due to the reduction of antioxidant substances and an increased lipid peroxidation. The authors summarize the results obtained evaluating the auditory and vestibular functions and the inner ear hair cell morphology and survival after administration of antioxidant agents against cisplatin and gentamicin. In the first experiment, albino guinea pigs were treated with gentamicin (100 mg/kg per day, i.m.) alone or gentamicin (100 mg/kg per day, i.m.) plus alpha-tocopherol (100 mg/kg per day, i.m.) for 2 weeks. In a second experiment, albino guinea pigs were injected with cisplatin (2.5 mg/kg per day) or cisplatin (2.5 mg/kg per day) plus tiopronin (300 mg/kg) for 6 days. Electrocochleographic recordings were made from an implanted round window electrode. In all experiments compound action potentials (CAPs) were measured at 2-16 kHz. Changes in cochlear function were characterized as CAP threshold shifts. To evaluate vestibular function, the animals underwent sinusoidal oscillations in the dark about their vertical and longitudinal axes to evoke horizontal and vertical vestibulo-ocular reflexes (VOR). Frequency stimulation parameters ranged from 0.02 to 0.4 Hz and peak-to-peak amplitude was 20 degrees. Morphological changes were analysed by light microscopy and scanning electron microscopy. Both hearing loss and vestibular dysfunction induced by gentamicin were significantly attenuated by alpha-tocopherol. However, tiopronin co-therapy slowed the progression of hearing loss in cisplatin-treated animals and significantly attenuated the final threshold shifts. Cisplatin had little effect on the hair cells of cristae ampullares and maculae. Vestibular function was completely preserved in tiopronin co-treated animals. In conclusion, antioxidants such as alpha-tocopherol or tiopronin interfere with gentamicin and cisplatin damage and this suggests that they may be useful in preventing oto-vestibulotoxicity. Therefore, it is important to develop protective strategies that permit the avoidance of the toxic side effects of these drugs without interfering with their therapeutic effects.

Action Potentials↗
PubMed2002

Cerebellar nodulectomy impairs spatial memory of vestibular and optokinetic stimulation in rabbits.

Natural vestibular and optokinetic stimulation were used to investigate the possible role of the cerebellar nodulus in the regulation and modification of reflexive eye movements in rabbits. The nodulus and folium 9d of the uvula were destroyed by surgical aspiration. Before and after nodulectomy the vertical and horizontal vestibuloocular reflexes (VVOR, HVOR) were measured during sinusoidal vestibular stimulation about the longitudinal (roll) and vertical (yaw) axes. Although the gain of the HVOR (G(HVOR) = peak eye movement velocity/peak head velocity) was not affected by the nodulectomy, the gain of the VVOR (G(VVOR)) was reduced. The gains of the vertical and horizontal optokinetic reflexes (G(VOKR), G(HOKR)) were measured during monocular, sinusoidal optokinetic stimulation (OKS) about the longitudinal and vertical axes. Following nodulectomy, there was no reduction in G(VOKR) or G(HOKR). Long-term binocular OKS was used to generate optokinetic afternystagmus, OKAN II, that lasts for hours. After OKAN II was induced, rabbits were subjected to static pitch and roll, to determine how the plane and velocity of OKAN II is influenced by a changing vestibular environment. During static pitch, OKAN II slow phase remained aligned with earth-horizontal. This was true for normal and nodulectomized rabbits. During static roll, OKAN II remained aligned with earth-horizontal in normal rabbits. During static roll in nodulectomized rabbits, OKAN II slow phase developed a centripetal vertical drift. We examined the suppression and recovery of G(VVOR) following exposure to conflicting vertical OKS for 10-30 min. This vestibular-optokinetic conflict reduced G(VVOR) in both normal and nodulectomized rabbits. The time course of recovery of G(VVOR) after conflicting OKS was the same before and after nodulectomy. In normal rabbits, the head pitch angle, at which peak OKAN II velocity occurred, corresponded to the head pitch angle maintained during long-term OKS. If the head was maintained in a "pitched-up" or "pitched-down" orientation during long-term OKS, the subsequently measured OKAN II peak velocity occurred at the same orientation. This was not true for nodulectomized rabbits, who had OKAN II peak velocities at head pitch angles independent of those maintained during long-term OKS. We conclude that the nodulus participates in the regulation of compensatory reflexive movements. The nodulus also influences "remembered" head position in space derived from previous optokinetic and vestibular stimulation.

Animals↗
PubMed2002

Angiotensin II stimulates contraction and growth of testicular peritubular myoid cells in vitro.

Seminiferous tubule contraction, an important step in the regulation of spermatogenesis and testicular sperm output, is regulated by several agonists. In the present paper, we investigated whether angiotensin II (Ang II) may have a place among them. In binding experiments performed to assess the presence of specific receptors in rat peritubular myoid cells (TPMC), binding of (125)I-Ang II to TPMC was saturable in a time-dependent manner. Competition binding experiments performed with Losartan and PD 123319 showed that Losartan was able to inhibit the binding of (125)I-Ang II, whereas PD 123319 was ineffective. Ang II induced a dose-dependent rise in intracellular Ca(2+). Depletion of intracellular calcium stores by thapsygargin resulted in a lower rise of intracellular calcium, and the L-type voltage-operated calcium channel (VOCC-L) blocker verapamil abolished the Ca(2+) influx in rat TPMC. Altogether, these findings indicate that the Ang II-induced increase in [Ca(2+)](i) involves both extracellular influx and Ca(2+) release from intracellular stores. Ang II induced a dose-dependent TPMC contraction, and Losartan and not PD 123319 inhibited the response. Ang II-induced contraction was inhibited by adrenomedullin, previously shown to antagonize endothelin 1-provoked contraction in those cells. Ang II elicited (3)H-thymidine DNA incorporation and proliferation in a dose-dependent manner in TPMC. Losartan and both MAPK inhibitor PD 98059 and tyrosine kinase inhibitor AG18 were able to inhibit Ang II-induced (3)H-thymidine uptake and cell proliferation. In conclusion, the present study documents that angiotensin II, the active mediator of the tissue and circulating renin-angiotensin system present in the mammalian testis, induces contraction, growth and rise in intracellular calcium in rat peritubular myoid cells via angiotensin II type 1 receptors, and suggests that Ang II is involved in the paracrine regulation of the seminiferous tubule function.

Angiotensin II↗
PubMed2001

Eye instability induced by vestibular stimulation in rabbits.

The slow compensatory phases of the vestibulo-ocular reflex (VOR) in the rabbit tend to drift and the drift reverses the direction. This periodic alternating drift (PAD) has two peculiar characteristics: (1) it is induced by sinusoidal vestibular stimulation in naive animals, being evoked immediately after stimulus onset and persisting after the end of stimulation; (2) the peak velocity and period of the drift are dependent on stimulus amplitude. PAD of the rabbit has strong similarities with PAN, a periodic alternating nystagmus observed in humans with cerbellar disorders and in monkeys after nodulo-uvulectomy, although its peak velocity is smaller. It is hypothesized that PAD is due to a slight instability, caused by vestibular stimulation in darkness, of the cerebellar adaptive loop, which exerts a variable gain control on the time constant of the velocity storage integrator.

Animals↗
PubMed2001

Functional recovery after extra-ocular muscle deafferentation in the rabbit.

The present research analysed on chronic animals the functional recovery of eye motility after impairment of the proprioceptive input at the level of the semilunar ganglion. The horizontal vestibulo-ocular reflex (HVOR) was recorded in normal pigmented rabbits before and after a partial electrolytic lesion of the semilunar ganglion. The recordings were repeated daily for 8-10 days to evaluate the recovery. Immediately after the lesion, as previously observed, HVOR slow phases were unaffected, while quick phases (QPs) showed a reduction in peak velocity and a deviation of trajectories from the horizontal plane. QP peak velocity was almost completely restored within 3-5 days, while trajectory deviation was not corrected during the observation period. Furthermore, in some animals, the variability of trajectories showed, starting from days 3-5, a progressive increase that led to a greater spatial disorganization. A process of lesion-induced plasticity takes place. but only the velocity of QPs can be recovered rapidly, while the QP trajectory impairment does not appear to be compensated substantially, which underlines a determinant role in the control of QP spatial orientation exerted by EOM proprioceptive signals.

Afferent Pathways↗
PubMed1999

Optokinetic and vestibular stimulation determines the spatial orientation of negative optokinetic afternystagmus in the rabbit.

Prolonged binocular optokinetic stimulation (OKS) in the rabbit induces a high-velocity negative optokinetic afternystagmus (OKAN II) that persists for several hours. We have taken advantage of this uniform nystagmus to study how changes in static head orientation in the pitch plane might influence the orientation of the nystagmus. After horizontal OKS, the rotation axis of the OKAN II remained almost constant in space as it was kept aligned with the gravity vector when the head was pitched by as much as 80 degrees up and 35 degrees down. Moreover, during reorientation, slow-phase eye velocity decreased according to the head pitch angle. Thereafter, we analyzed the space orientation of OKAN II after optokinetic stimulation during which the head and/or the OKS were pitched upward and downward. The rotation axis of OKAN II did not remain aligned with an earth vertical axis nor a head vertical axis, but it tended to be aligned with that of the OKS respace. The slow-phase eye velocity of OKAN II was also affected by the head pitch angle during OKS, because maximal OKAN II velocity occurred at the same head pitch angle as that during optokinetic stimulation. We suggest that OKAN II is coded in gravity-centered rather than in head-centered coordinates, but that this coordinate system may be influenced by optokinetic and vestibular stimulation. Moreover, the velocity attenuation of OKAN II seems to depend on the mismatch between the space-centered nystagmus rotation axis orientation and that of the "remembered" head-centered optokinetic pathway activated by OKS.

Animals↗
PubMed1997

Otolithic and extraocular muscle proprioceptive influences on the spatial organization of the vestibulo- and cervico-ocular quick phases.

The cervico-ocular reflex (COR) was studied alone or in combination with the vestibulo-ocular reflex (VOR) in the rabbit. Step stimulations of the body with respect to the fixed head induced small slow compensatory responses followed by large compensatory quick phases (QP). These responses remained aligned with the horizon at different head pitch angles. The QP reorientation in space was due to the gravity influence on the otolithic receptors. The vestibular induced QPs exhibit a similar pattern. Because of this reorientation, the reduction of the amplitude of the vestibular induced QPs, due to the addition of the COR, was maintained even at different static head positions. The electrolytic lesion of the ophthalmic branch of the trigeminal nerve deeply affected the space orientation of the COR. In particular, the cervically induced compensatory QPs of the eye ipsilateral to the lesion showed a remarkable variability of their trajectories and they lost space reorientation. These findings suggest that the coordinate system controlling the QPs is influenced by signals originating from both head position in space and eye position in the orbit.

Animals↗
PubMed1996

Influence of the extraocular muscle proprioceptors on the orientation of the vestibulo-ocular reflex.

In the intact brain lamb, unilateral electrolytic lesion of the medial dorso-lateral portion of the semilunar ganglion containing the first order neurons of the eye muscle proprioception induced modifications of the horizontal and vertical vestibulo-ocular reflex (HVOR and VVOR) which consisted in marked alterations of the trajectories of the quick phases, while the slow phases were scarcely affected. Similar results were observed after section of the branches described by Winckler in the retrobulbar region along the extraocular muscle proprioceptive information travels. These findings extend those of previous investigations carried out in decorticate animals.

Animals↗
PubMed1995

Influence of gravity on the orientation of vestibular induced quick phases.

In rabbits and cats the orientation of the quick phases (QPs) of the vestibulo-ocular reflex (VOR) was studied varying the head position in space. At different head tilt positions, QPs induced by step vestibular stimulation disaligned with respect to the stimulus toward the orientation of the earth's horizontal axis. The rabbits' QPs were horizontal during yaw stimulation and remained horizontal in a range of head pitch of +/- 90 degrees (reorientation gain = 1). Therefore, the slow compensatory responses (CSPs) progressively disaligned compared with the QPs. QPs induced by roll stimulation also showed horizontal orientation, although these were rare in the upright position and occurred more frequently when the head was pitched. In cats only the yaw-induced QPs were coplanar with the stimulus, while QPs induced by pitching were mostly oblique. It followed that in either yawing or pitching, the QPs had their end point scattered within a horizontally elongated area of the visual field. When tilting cats in the frontal plane, the orientation of QP trajectories changed with respect to the stimulus so that the end point distribution tended to remain aligned toward the horizontal instead of being fixed in the orbit. The reorientation gain decreased from 1 to 0.5 by increasing the head tilt. On the basis of difference regarding eye implantation and motility it was suggested that the effect of gravity on the orientation of QPs could be aimed at maintaining the interocular axis aligned with the horizon in the rabbit and at orientating the visual scanning system in the horizontal plane in the cat.

Animals↗
PubMed1995

Extraocular muscle proprioception and eye position.

In the lamb, acute unilateral section of the ophthalmic branch induced in the ipsilateral eye occasional oscillations of the resting position and misalignment of the horizontal vestibulo-ocular reflex (HVOR) with respect to the stimulus. Additional electrolytic lesion of the cells innervating the proprioceptors of the medial rectus muscle, or of the lateral rectus muscle in the contralateral semilunar ganglion, provoked a 4 degrees-7 degrees consensual eye deviation towards and away from the lesioned side, respectively. The optokinetic beating field was similarly deviated. Under these experimental conditions, HVOR showed enhanced gain and marked misalignment in both eyes. Therefore, the selective suppression of muscular proprioceptive input deviated both eyes towards the direction opposite to the muscle whose gangliar proprioceptive representation has been destroyed.

Animals↗
PubMed1994

The otolithic contribution to vertical ocular stability in the cat.

In cats, horizontal (HVOR) and vertical (VVOR) vestibulo-ocular reflexes were studied alone and combined with optokinetic stimulation. The upright VVOR (VVOR O degree) only showed higher gain and smaller phase lead compared to those of HVOR at frequencies below 0.05 Hz. The addition of optokinetic stimulation to the vestibular stimulation increased the gain of the horizontal and vertical ocular responses close to 1. VVOR was also studied in side down position (VVOR 90 degrees). In VVOR 90 degrees the ocular responses were asymmetric. The downward directed eye responses of VVOR 90 degrees showed lower gain and greater phase lead compared to those of VVOR 0 degree for the whole range of tested frequencies (0.01-0.4 Hz), while the upward eye responses only showed a lower gain at the lower range of frequencies tested. In the light the gain of VVOR 90 degrees increased, but the gain of downward directed eye responses was consistently lower than 1 at lower frequencies. The higher gain of the VVOR 0 degree compared to the VVOR 90 degrees and HVOR was attributed to the maculo-ocular reflex (MOR) evoked by the gravity modulation of the otolithic receptors, when the animals were oscillated in the pitch plane. The MOR was isolated from the VVOR 0 degree by plugging all semicircular canals. At very low frequencies the gain of the MOR was 0.3-0.35 and the phase was close to 0 degree. This reflex showed a progressive gain decrease and phase lag by increasing the stimulation frequencies. This suggests a low pass filtering process of the otolithic signal. Furthermore in plugged animals the asymmetry of the vertical optokinetic responses was reduced by adding the MOR. The quick phases (QPs) of the vestibular responses were also different depending upon the stimulation plane. The QPs of VVOR 0 degree were smaller and more delayed than those of HVOR and VVOR 90 degrees. In conclusion the main effects observed during otolithic coactivation in the VVOR 0 of the cat are: 1) the enhancement of gain and reduction of phase lead at low frequency vestibular stimulation, resulting in similar vertical and horizontal gaze stability; 2) the equalization of the upward and downward responses of both vestibulo-ocular and optokinetic responses; 3) the reduction of the amplitude and frequency of vertical quick phases.

Animals↗
PubMed1993

Gravity load related asymmetries in the sagittal vestibulo-collic reflex.

EMG recordings of the neck muscles (biventer cervicis, complexus, splenius, longus capitis) of decerebrate cats were obtained during pitch and roll stimulations (sinusoidal stimulation: 30 degrees p-p amplitude, 0.2 Hz frequency). Most of the EMG responses to pitch showed activation peaks leading the position stimuli by 56 degrees and inhibition peaks leading by 11 degrees. Conversely, in response to roll the activation peak led by 16 degrees and the inhibition peak by 10 degrees. The activation peaks of the pitch responses were, thus, more asymmetric and more leading than those of the roll responses. Consequently, the harmonic distortion coefficient was significantly higher in pitch than in roll. Moreover, when the vertical semicircular canals were activated in absence of otolithic modulation, the pitch and roll responses maintained the same difference in timing observed in the presence of otolithic coactivation. It appeared that the simultaneous stimulation of both anterior semicircular canals (pitch) induces a greater lead than that of combined anterior and posterior canals (roll). Thus the timing of neck muscle responses to vestibular stimulation depends on the pair of activated vertical semicircular canals.

Animals↗
PubMed1993

Asymmetries in ocular and cervical responses to sagittal vestibular stimulations.

In rabbits and cats vestibulo-ocular reflex (VOR) and vestibulo-ocular reflex (VCR) were tested in frontal and sagittal planes. The VOR evoked by pitching the animals in side down position showed asymmetric responses with peak eye velocity higher in upward direction than in downward one. This asymmetry was abolished when pitching the animal in upright position. This indicate that the otolithic coactivation, occurring in upright position, symmetrizes canal-induced vertical responses. Vestibulo-ocular reflex evoked by rolling the animals was also symmetric, no matter the animal position was. The electromyographic response of neck muscles to sagittal VCR showed an asymmetric behaviour as far as the timing of extensor and flexor activation was concerning. In fact, the increase of extensor muscle activity was steeper than the decrease and the activation peak was more leading than the inhibition peak. The flexor muscles showed an opposite behaviour. This flexion-extension asymmetry was present either with or without otolithic coactivation. On the contrary, the EMG responses to frontal VCR were much more symmetric. It can be suggested that the upward preponderance is present in the sagittal vestibular circuitry to enhance the upward VCR against a gravity load which opposes head stability during downward head displacements. On the contrary, at level of the eye, in which the gravity does not oppose the responses, the canal-induced vertical asymmetry is cancelled by the otolithic coactivation.

Animals↗
PubMed1990

Hemodynamic effects of decompressive craniectomy in cold induced brain oedema.

An experimental model of cold induced brain oedema was carried out in 7 albino rabbits by topic application of fluid N2 on the skull to examine the favourable effects of an appropriate tailored craniodural opening both on the whole brain perfusion and on the local dynamics of the oedematous fluid. After positioning the animals in a stereotactic frame the following parameters were recorded: ICP, carotid blood pressure and flow velocity, EEG, EKG. Histological staining with Evan's blue was utilized to check fluid extravasation. In all the animals the lesion was followed both by an ICP increase and a reduction in the carotid blood flow velocity so indicating an increase in the cerebrovascular resistances. In 4 animals the removal of the craniodural flap over the lesion dramatically reduced the ICP values and normalized the blood flow velocity. No difference in the Evan's blue distribution was noticed between the two groups of animals.

Animals↗
PubMed1990

The impact of different dosing regimens of the aminoglycosides netilmicin and amikacin on vestibulotoxicity in the guinea pig.

The purpose of this study was to assess whether vestibulotoxicity caused by aminoglycoside antibiotics is influenced by the treatment schedule used: i.e., a single high dose given once daily (o.d.) vs multiple divided doses (tres in die, t.i.d.). Two groups of guinea pigs (5 animals/group) were injected intramuscularly for 21 days with either netilmicin or amikacin 150 mg/kg o.d., whereas other groups received each drug at 50 mg/kg t.i.d. at 8-h intervals. Amikacin was also given at 225 mg/kg o.d. and 75 mg/kg t.i.d. Vestibular functions were assessed by measuring vestibulo-ocular reflexes. Acoustic function was also evaluated by measuring Preyer's pinna reflex. Sensory epithelia of the inner ears were evaluated histologically under a scanning electron microscope. Netilmicin failed to affect either the vestibular or the acoustic apparatus in the animal groups receiving the two dosing regimens. Amikacin in a dose of 150 mg/kg per day induced an acoustic deficit which was more severe in the t.i.d. group. The higher dose of amikacin provoked significant lesions of acoustic and vestibular function, irrespective of the dosing regimen used. These data suggest that the o.d. dosing regimen of the aminoglycoside antibiotics might provide effective treatment for infectious diseases without enhancing the risk for vestibular and acoustic side effects.

Acoustic Stimulation↗