Biomedical subjects

J Gallar

Publications and source records attributed to J Gallar.

29 records · Page 2Linked to original sources

PubMed1995

Influence of diltiazem on the ocular irritative response to nitrogen mustard.

Application of nitrogen mustard to the eye of rabbits causes an anterior segment irritation and a biphasic elevation of intraocular pressure. This intraocular pressure response is composed of an initial peak, produced by neuropeptides released by excited sensory nerves, and a second, slower rise due to prostaglandins. We studied the effect of diltiazem, a calcium antagonist that selectively blocks chemical excitation of sensory nerves, on the inflammatory response to nitrogen mustard. In adult rabbits, intraocular pressure was determined by pneumatonometry; pupil diameter and palpebral opening were measured with a ruler while conjunctival vasodilation, edema and secretion were scored in subjective units (0-8). Aqueous humor protein content was analysed at the end of the experiment. Bilateral application of 1% nitrogen mustard evoked within the first 6 hr an intraocular pressure elevation followed by ocular hypotony, miosis, palpebral closure, conjunctival vasodilation, edema and an elevation of aqueous proteins. Topical application of 10 mM diltiazem, prior to administration of nitrogen mustard elicited by itself a transient, small intraocular pressure increase and reduced significantly the acute intraocular pressure elevation and conjunctival vasodilation evoked by the irritant; delayed conjunctival edema and palpebral closure were also attenuated by 10 mM diltiazem. The decrease of miotic response and of aqueous humor protein content was not significant. Diltiazem at 2.8 mM was effective only in reducing significantly conjunctival edema and vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

PubMed1995

Irritation of the anterior segment of the eye by ultraviolet radiation: influence of nerve blockade and calcium antagonists.

The aim of this investigation was to determine the influence on anterior segment inflammation elicited by UV radiation, of ocular denervation and pharmacological blockade of sensory nerve fibers with capsaicin, tetrodotoxin and calcium antagonists. Both eyes of pigmented rabbits were exposed for 5 min to UV radiation (254 nm); 24 h later, inflammatory signs were evaluated by biomicroscopy of the corneal epithelium, the stroma and the endothelium and scored from 0 to 4. Conjunctival vasodilation and miosis were also assessed. Two weeks before UV exposure, a group of rabbits received a retrobulbar injection of ethanol or of 1% capsaicin. Intact, capsaicin-treated and alcohol-denervated animals were treated topically, prior to UV exposure, with tetrodotoxin (0.78 mM) and the calcium antagonists diltiazem (1-28 mM) and nifedipine (10 mM). UV radiation produced at 24 h signs of corneal irritation, conjunctival hyperemia, miosis and elevated protein content of the aqueous humor. Retrobulbar injection of 99% alcohol or 1% capsaicin did not diminish significantly the inflammation of tissues directly exposed to UV radiation, although extension of inflammatory signs to unaffected areas was prevented. Pre-treatment of normal and denervated eyes with diltiazem attenuated UV-induced eye irritation signs at concentrations of 10 mM or over. The effect was less pronounced with tetrodotoxin and was not obtained with nifedipine. These findings suggest that the contribution of a neurogenic mechanism to anterior segment inflammation induced by UV exposure is modest. They also show that high concentrations of diltiazem, but not of nifedipine, effectively reduced inflammation of the anterior segment of the eye evoked by UV radiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Response of sensory units with unmyelinated fibres to mechanical, thermal and chemical stimulation of the cat's cornea.

1. In the cat anaesthetized with sodium pentobarbitone, electrical activity was recorded from single unmyelinated sensory fibres innervating the cornea. 2. Based on their response to mechanical (calibrated aesthesiometer), chemical (10 mM acetic acid or 616 mM NaCl) and thermal (cooling from 35 to 5 degrees C; heating to 51 degrees C) stimuli, corneal unmyelinated fibres were classified as polymodal (71%) or 'cold' nociceptors (29%). 3. Polymodal units responded to mechanical indentation of the cornea and developed fatigue after repeated stimulation. They were excited by temperatures over 37 degrees C and exhibited sensitization to repeated heating. 4. Corneal polymodal units were also activated by topical application of 10 mM acetic acid and hypertonic NaCl (616 mM). Capsaicin (0.33 mM) elicited a discharge of impulses that was followed by inactivation to mechanical, chemical and thermal stimuli. 5. 'Cold' nociceptors had small receptive fields, preferentially located at the periphery of the cornea. They were excited by small temperature decreases of the corneal surface in a range between 30 and 8 degrees C, but were not responsive to noxious heat. 6. 'Cold' nociceptors encoded temperature changes between 35 and 23 degrees C. The discharge was proportional to the velocity of the temperature drop; sustained temperatures were not signalled by changes in static frequency values. 'Cold' nociceptive fibres responded to hypertonic NaCl (616 mM) and weakly to 10 mM acetic acid. Capsaicin (0.33 mM) first excited and then inactivated 'cold' nociceptors. 7. Thermoreceptive fibres were found in the episclera. They fired in bursts and responded to small temperature decreases, but were insensitive to irritant chemical and capsaicin.

Acetates↗

PubMed1993

Reduction of capsaicin-induced ocular pain and neurogenic inflammation by calcium antagonists.

PURPOSE: To examine whether blockade of chemosensitivity of corneal nociceptors by Ca2+ antagonists decreases pain and irritation induced by capsaicin. METHODS: In adult rabbits, the number of lid-squeezing movements and the degree of palpebral opening, miotic response, and conjunctival vasodilation evoked by a bilateral instillation of 30 microliters of capsaicin (33 mM) were measured at different times (up to 5 hours) after the drug. Irritative responses to capsaicin in eyes pretreated with diltiazem, verapamil, or nifedipine were compared with those that received only the vehicle. Protein content in aqueous humor was also measured at the end of the experiment. RESULTS: Diltiazem at doses of 1 to 28 mM, administered 15 minutes before the application of capsaicin, significantly decreased scratching movements, conjunctival hyperemia, closure of the eye, and elevated aqueous protein concentration induced by capsaicin; however, it did not significantly reduce miosis. Nifedipine (2.8 and 10 mM) diminished the number of scratching movements but not other inflammatory parameters, whereas verapamil (2.8 and 10 mM) was totally ineffective in attenuating ocular signs of irritation produced by capsaicin. CONCLUSIONS: These results suggest that by lowering capsaicin-induced neural activity in nociceptive terminals, diltiazem decreases pain and neurogenic inflammation and may be useful as both an analgesic and an antiinflammatory agent in the eye.

Animals↗

PubMed1993

Stimulation of the cervical sympathetic nerves increases intraocular pressure.

PURPOSE: To test the hypothesis that a moderate electrical stimulation of the cervical sympathetic nerves in rabbits can increase intraocular pressure (IOP). METHODS: Electrical stimulations of the cervical sympathetic nerves were performed in anesthetized and conscious rabbits. Intraocular pressure, pupil size, and concentrations of aqueous humor components were monitored. RESULTS: In urethane-anesthetized rabbits, stimulations of 5 V and 1 ms at 2.5 Hz for 1 hr and then at 20 Hz for 2 hr caused a short inhibition of IOP decrease and a prolonged mydriasis. Concentrations of norepinephrine (NE), neuropeptide Y (NPY), and cyclic AMP (cAMP) in aqueous humor were elevated. Aqueous humor protein concentration was not changed. In rabbits anesthetized with ketamine, chlorpromazine, and pentobarbital, electrical stimulations with the same parameters caused prolonged increases in IOP and pupil size. Aqueous humor NE and cAMP concentrations increased, while NPY and protein concentrations did not change. When the stimulations were set at 5 Hz for 3 hr under this anesthesia, the increase of IOP and mydriasis persisted. However, only the NE concentration increased. In conscious rabbits, stimulations of 5 V and 1 ms at either 5 Hz or 20 Hz were delivered from a portable stimulator for 4 hr, starting 2 hr before the onset of the dark. Stimulations at 5 Hz caused an increase in IOP in the light phase. The circadian IOP elevation in the dark phase persisted. When 20 Hz was used, a transient fall in IOP was observed, and the circadian IOP elevation was eliminated. Aqueous humor NE concentration doubled in conscious rabbits receiving electrical stimulations at 5 Hz for 1 hr. CONCLUSIONS: A moderate electrical stimulation of the cervical sympathetic nerves can increase IOP in anesthetized rabbits and in conscious rabbits in the light phase.

Anesthetics↗

PubMed1992

Blockade by calcium antagonists of chemical excitation and sensitization of polymodal nociceptors in the cat's cornea.

1. The possibility that a modified Ca2+ channel mediates chemical and thermal excitation of nociceptors was examined in single polymodal nociceptive fibres of the cat's cornea. 2. Ca2+ channel blockers cadmium (2.5 mM) and diltiazem (1 mM), and high external [Ca2+] (40 mM), markedly reduced nociceptive responses to topical acidic solutions (pH 4.5). 3. Decreasing the pH to 6.5 did not cause excitation, but reduced the subsequent response to pH 4.5 buffer. 4. Diltiazem (1 mM), applied after repeated stimulation with stepped heating pulses (35 to 47-49 degrees C in 2 degrees C steps) decreased the impulse responses elicited by heat. The decrease in threshold to thermal stimulation produced by repeated heating was blocked by diltiazem. 5. Mechanical threshold and mechanical responsiveness of corneal polymodal nociceptors was not modified by Ca2+ antagonists or by a high-Ca2+ solution. 6. These results offer indirect evidence that proton-activated Ca2+ channels mediate stimulation of nociceptors by acidic solutions. The same type of ionic channel appears to be involved in the response of nociceptors to heat and in sensitization, but not in their responsiveness to mechanical stimulation. The blockade of nociceptive responses by Ca2+ antagonists opens the possibility of using Ca2+ blockers as selective analgesic drugs.

Animals↗

PubMed1991

Excitation by irritant chemical substances of sensory afferent units in the cat's cornea.

1. Single-unit electrical activity was recorded from thin myelinated sensory nerve fibres innervating the cornea of deeply anaesthetized cats. 2. Based on their responses to mechanical (calibrated von Frey hairs), chemical (10 mM-acetic acid and/or 616 mM-NaCl) and thermal (ice-cold or heat up to 51 degrees C) stimuli, corneal A delta fibres were classified as polymodal nociceptors (63%), high-threshold mechanoceptors (22%) and mechano-heat nociceptors (15%). Thin myelinated fibres responding only to cold were found in the limbus of the eye. 3. Application of 10 mM-acetic acid on the corneal surface for 30 s evoked in polymodal fibres a brisk discharge of impulses often followed by a low-frequency impulse activity. NaCl (616 mM) produced a more gradual and sustained firing response. 4. The responses of polymodal fibres to acid were proportional to extracellular pH values (pH range: 4.5-6.0). After sensitization to repeated heating, most mechano-heat units developed a sensitivity to acidic stimulation. 5. Topical 0.33 mM-capsaicin excited polymodal nociceptors of the cornea; 5 min after capsaicin about 15% of these fibres were inactivated to all subsequent stimuli. In the rest of the fibres, chemical and thermal sensitivity disappeared after 0.33-3.3 mM-capsaicin, but mechanosensitivity was preserved. 6. Corneal mechanoceptors and limbal cold receptors were not affected by capsaicin (up to 33 mM). 7. These experiments demonstrate that the cornea of the cat is innervated by polymodal as well as mechanoceptive A delta nociceptors. In polymodal nociceptive fibres, mechanical and chemical sensitivities appear to be subserved by separate transduction mechanisms.

Acetates↗

PubMed1990

Effects of capsaicin on corneal wound healing.

This study examined whether the depletion of neuropeptides from sensory nerve terminals induced by capsaicin modifies the healing rate of experimental corneal wounds in adult rabbits. Capsaicin (33 or 3.3 mM solutions) was administered topically and/or by a single retrobulbar injection to one eye while the fellow eye, treated with the vehicle, served as a control. After 1-3 weeks of treatment, an epithelial wound was made in the center of the cornea of both eyes with n-heptanol. Migration rates of epithelial cells surrounding the wound and estimated wound closure times were calculated by measuring the reduction in wound size. Combined treatment with 33 mM retrobulbar and 3.3 mM topical capsaicin for 3 weeks induced a significant delay in epithelial migration rates and in wound closure times (P less than 0.05). Topical or retrobulbar capsaicin alone for 3 weeks and combined treatment lasting only 1 week were not sufficient to modify wound healing times. The substance P antagonist, spantide (3 mM), applied topically for 1-3 weeks before or immediately after corneal wounding was also ineffective in changing wound closure rates. These findings suggest that the delayed wound healing observed after prolonged treatment with capsaicin could be due to a sustained depletion of neuropeptides from corneal sensory endings, supporting the hypothesis that trophic effects of sensory nerves on corneal epithelium are, at least in part, mediated by neuropeptides contained in peripheral nerve terminals.

Administration, Topical↗

PubMed1987

Chronic stimulation of ocular sympathetic fibers in unanesthetized rabbits.

The goal of this study was to devise a technique to implant permanent electrodes in the cervical sympathetic trunk, to stimulate the ocular adrenergic fibers for periods of hours or days in awake, unrestrained rabbits. Electrodes were made of a silver wire soldered to a multistranded wire and enclosed in silicone. Two of these electrodes were wrapped around the preganglionic sympathetic nerve, their leads emerging through a hole in the back of the neck. Success of the procedure was confirmed by the mydriasis elicited by electrical stimulation of the nerve following surgery; threshold voltages for the pupillary response varied between 5-10 volts. In eight rabbits, suprathreshold sympathetic stimulation was performed on the following days by means of a portable stimulator using increasing frequencies (1, 3, 5, 8, and 10 Hz) during a 20-hr period. Dilation of the ipsilateral pupil and vasoconstriction in the ear, measured by the fall in temperature of the ear's surface, was observed as long as stimulation was maintained. Both effects were proportional to the frequency of stimulation. Maximal mydriasis was obtained at 8 Hz, whereas full vasoconstriction was elicited with 5 Hz. Intraocular pressure, measured in 10 rabbits with a Perkins tonometer at the end of a 24-hr stimulation period, did not differ from pre-stimulation values. It was concluded that chronic stimulation of the sympathetic nerve allows to maintain known levels of adrenergic activity in the eye, and may be a useful method to study the actions of the adrenergic system on various ocular functions in unanesthetized animals.

Animals↗

PubMed1987

Effects of chronic sympathetic stimulation on corneal wound healing.

To explore the possibility that adrenergic fibers influence epithelial wound healing in the rabbit cornea, chronic electrodes were implanted in the left cervical sympathetic nerve, and symmetrical wounds were produced on the corneal epithelium of both eyes by means of n-heptanol. Continuous sympathetic stimulation was applied to awake, unrestrained animals during the wound-healing process (2-3 days) by use of a portable stimulator that delivered 1 ms, 3-Hz electric pulses at an amplitude necessary to evoke mydriasis. Migration rates of epithelial cells surrounding the wound and estimated wound closure times were calculated by measuring the reduction in wound size. In stimulated corneas, the epithelial migration rate was smaller (36.9 +/- 6.2 microns/hr) than in control corneas (49.4 +/- 5.4 microns/hr), the differences being significant (P < 0.05). Significant differences in wound closure times between stimulated (53.2 +/- 6.8 hr) and control (41.3 +/- 5.5 hr) corneas were also observed. These results suggest a modulatory influence of corneal adrenergic fibers on the processes that follow epithelial injury of the cornea.

Adrenergic Fibers↗

PubMed1985

Citrate determination with aconitase immobilized on solid support.

Pig heart aconitase has been immobilized on Enzacryl AA solid support and its kinetic behaviours were studied by using a stirred bath reactor with continuous recycling. In this reactor, the best flow rate has been determined to eliminate diffusional problems. Kinetics constants, thermic stability and pH variations have been compared between the soluble and immobilized aconitase for determination of enzyme-Enzacryl AA effectivity. Stability of the soluble and immobilized aconitase was also studied after repeated use and long-time storage. While the soluble form loses its activity after 24 hr storage, the immobilized form preserves its full activity after repeated usage and long-lasting storage. Finally, an easily measurable parameter has been found to quantitate citrate. The maximum increase of absorbance, is proportional to citrate concentration in a range between 0.2 and 3.2 mM. In conclusion, these results show that the immobilized aconitase system can be used for the determination of citrate with reproductility and great sensitivity. In addition to the simplicity of the assay, great economy in enzyme consumption has been demonstrated, in contrast to the traditional methods of quantitative citrate analysis.

Aconitate Hydratase↗