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At least 955 records · Page 53Linked to original sources
PubMed1995

The effects of endothelin-1 on isolated bovine ciliary muscles.

The effects of endothelin-1 on bovine ciliary muscle were investigated in vitro using muscle strips prepared in two different directions (longitudinal and circular). Fifty-two bovine ciliary muscle strips (4 x 6 mm) were prepared. Chemicals were added to both types of strips suspended in an organ chamber, and their changes in isometric tension were recorded. The concentration-response relationship of endothelin-1 (n = 20), the magnitudes of contractions caused by endothelin-1 and carbachol (n = 12), and the effects of an endothelin receptor subtype A antagonist BQ123 (n = 4) and an endothelin receptor subtype B agonist IRL1620 (n = 4) were studied. The cumulative addition of endothelin-1 caused relaxation at low concentrations (10(-11) and 10(-10) M), while it caused contraction of the ciliary muscles at high concentrations (10(-9), 10(-8) and 3 x 10(-8) M). The magnitude of the contraction caused by 10(-8) M endothelin-1 was about 30% in the longitudinal muscle strips and 29% in the circular muscle strips, relative to the contraction caused by 10(-5) M carbachol, a muscarinic agonist. The contractile response caused by 10(-8) M endothelin-1 was abolished and converted to relaxation by pretreatment with BQ123, a selective endothelin receptor subtype A antagonist. Single addition of IRL1620, a selective endothelin receptor subtype B agonist, caused only relaxation. These results suggest that, endothelin-1 causes not only contraction at high concentrations, but also relaxation at low concentrations in bovine ciliary muscle. Also, it suggested that the relaxation is mediated by endothelin receptor subtype B, whereas the contraction is mediated by endothelin receptor subtype A.

Animals↗
PubMed2004

[Usefulness of oral pilocarpin therapy in the treatment of xerostomia and xerophthalmia in patients with primary Sjögren's syndrome].

BACKGROUND AND OBJECTIVE: We aimed to asses the efficacy of pilocarpine tablets as a symptomatic treatment for dry mouth and dry eyes in patients with primary Sjögren's syndrome (SS). PATIENTS AND METHOD: We included 40 patients with SS (38 women and 2 men), mean age 49.2 years (range, 35-68), with severe xerostomia and xerophthalmia. Objective tests (salivary scintigraphy, Schirmer's test, break-up time, Rose Bengal staining) and subjective tests (symptoms' questionnaire) were carried out before starting treatment and 6 months later to evaluate any glandular function improvement. RESULTS: All patients initially received 15 mg daily of pilocarpine. Twelve (30%) patients received 20 mg daily. Dry mouth-related symptoms improved in 57.5% of patients and dry eyes-related ones improved in 35%. Scintigraphic studies demonstrated an objective improvement of the glandular function in 35% patients. Ocular tests showed an improvement in 30% cases. CONCLUSIONS: Pilocarpine therapy is useful to improve xerostomia and xerophthalmia in SS patients with moderate and severe glandular involvement. However, we have not observed a good correlation between subjective improvement of symptoms and the objective test results.

Administration, Oral↗
PubMed1983

Glaucoma in children.

Successful management of glaucoma to prevent blindness depends upon early recognition of the condition. This article details the early signs and symptoms of glaucoma so that prompt referral for care and treatment may be facilitated.

Abnormalities, Multiple↗
PubMed2003

Targeting outflow facility in glaucoma management.

Glaucoma is often characterized by decreased pressure-sensitive aqueous outflow through the trabecular meshwork. This defect in pressure-sensitive aqueous outflow is evident from the low tonographic facility of outflow ("C") measured in many patients. The impairment in outflow facility causes the high intraocular pressure (IOP) and large diurnal IOP fluctuations often found in glaucoma. Because large diurnal IOP fluctuations have been shown to be a risk factor for glaucomatous progression, IOP-lowering therapy should aim to achieve a low, stable IOP. Pressure-sensitive aqueous outflow helps prevent and dampen pressure spikes; thus, drugs that enhance outflow facility, in particular, may stabilize as well as lower IOP. Outflow facility is an attractive target for glaucoma treatment because enhancing outflow facility tends to restore the self-regulating tendency of IOP. Older drugs such as the cholinergic pilocarpine and the catecholamine epinephrine act primarily by improving outflow facility. This action is also important for the recently introduced prostamide, bimatoprost, as well as for the prostaglandin prodrug, latanoprost. Realization of the importance of facility of outflow in lowering and stabilizing IOP will stimulate additional research into the mechanism of action of ocular hypotensive agents and will help optimize the medical treatment of glaucoma.

Antihypertensive Agents↗
PubMedDate not supplied

A pharmacological examination of venoms from three species of death adder (Acanthophis antarcticus, Acanthophis praelongus and Acanthophis pyrrhus).

The common (A. antarcticus), northern (A. praelongus) and desert (A. pyrrhus) death adders are species belonging to the Acanthophis genus. The present study compared some pharmacological aspects of the venoms of these species and examined the in vitro efficacy of death adder antivenom. Neurotoxicity was determined by the time to produce 90% inhibition (t(90)) of indirect (0.1 Hz, 0.2 ms, supramaximal voltage) twitches in the chick biventer cervicis nerve-muscle (3-10 microg/ml) and mouse phrenic nerve-diaphragm (10 microg/ml) preparations. A. praelongus venom was significantly less neurotoxic than A. antarcticus venom but was not significantly different from A. pyrrhus venom. In the biventer muscle, all three venoms (3-10 microg/ml) abolished responses to exogenous ACh (1 mM) and carbachol (20 microM), but not KCl (40 mM), indicating activity at post-synaptic nicotinic receptors. All venoms (30 microg/ml) failed to produce significant inhibition of direct twitches (0.1 Hz, 2.0 ms, supramaximal voltage) in the chick biventer cervicis nerve-muscle preparation. However, A. praelongus (30 microg/ml) venom initiated a significant direct contracture of muscle, indicative of some myotoxic activity. The prior (10 min) administration of death adder antivenom (1 unit/ml), which is raised against A. antarcticus venom, markedly attenuated the twitch blockade produced by all venoms (10 microg/ml). Administration of antivenom (1.5 units/ml) at t(90) markedly reversed, over a period of 4 h, the inhibition of twitches produced by A. praelongus (3 microg/ml, 72+/-6% recovery) and A. pyrrhus (3 microg/ml, 51+/-9% recovery) but was less effective against A. antarcticus venom (3 microg/ml, 22+/-7% recovery). These results suggest that all three venoms contain postsynaptic neurotoxins. Death adder antivenom displayed differing efficacy against the in vitro neurotoxicity of the three venoms.

Acetylcholine↗
PubMed1997

Temporal filter of the motion sensor in glaucoma.

Glaucoma reportedly affects motion perception. As an initial step in characterizing glaucoma-induced changes in the motion system, we determined the range of temporal frequencies that the motion system could process. A noise-masking paradigm was used to measure contrast energy thresholds of 26 glaucoma patients at various stages of the disease and 16 age-similar subjects with normal vision. Using a sinusoidal stimulus, thresholds were measured for the discrimination of motion direction and for the stimulus embedded within a pattern of dynamic spatial noise. The noise was filtered to contain only low spatial frequencies, and the temporal-frequency spectrum of the noise was manipulated across conditions to derive the temporal filter shape of the most efficient motion sensor. The results show that the range of temporal frequencies processed by the motion system is diminished in the glaucoma group. The filters of the glaucoma subjects have reduced bandwidths compared with the normal-vision group. In addition, the upper cut-off frequency of the filters of the glaucoma subjects is correlated with stage of disease as indexed by the mean deviation of the Humphrey Visual Field Analyzer program 24-2, as well as the cup-to-disk ratio.

Adult↗
PubMed2001

Poly(2-hydroxyethyl methacrylate) film as a drug delivery system for pilocarpine.

This work investigates pilocarpine trapped in a matrix diffusion-controlled drug delivery system using hydrophilic inserts of Poly(2-hydroxyethyl methacrylate) (pHEMA) to ensure an increased bioavailability of pilocarpine and prolong the length of time in which the medication remains in the eyes of the test subjects. The physical and chemical properties of pilocarpine were investigated to elucidate the mechanism of drug-polymer interaction and the effect on drug release behavior of controlled release polymeric devices. In vitro release studies indicated that pilocarpine continued to be released from the inserts for a 24 h period. The results of intraocular pressure tests performed on albino rabbits were consistent with the observed in vitro behavior. The pressure decrease was significant for a period longer than 48 h. It confirms that the inserts, as sustainable releasing devices, are promising carriers for ophthalmic drug delivery systems.

Animals↗
PubMed1997

Intrathecal CGRP(8-37) results in a bilateral increase in hindpaw withdrawal latency in rats with a unilateral thermal injury.

The present study was performed to explore the effects of intrathecal administration of calcitonin gene-related peptide8-37 (CGRP(8-37)) on the hindpaw withdrawal latency (HWL) to pressure in rats with one thermally injured hindpaw. Furthermore, the interaction of CGRP(8-37)and naloxone was studied. Thermal injury was performed by dipping the left paw into 60 degrees C for 20 s. This induced a significant increase in the volume of the left hindpaw (P<0.001) and significant bilateral decreases of the latency of hindpaw withdrawal response to mechanical stimulation (Left: P<0.001; right: P<0.05). Intrathecal administration of 10, 20 and 40 nmol of CGRP(8-37), but not of 1 or 5 nmol, induced a significant bilateral increase in HWLs (P<0.001). The effect of CGRP(8-37) was partly reversed by intrathecal injection of naloxone at a dose of 32 and 64 microg respectively. Using radioimmunoassay, we found a significant bilateral increase in the concentration of CGRP-like immunoreactivity in the perfusate of both hindpaws 24 h after unilateral thermal injury (left: P< 0.001; right: P< 0.05). There was also an increase in the amount of CGRP-like immunoreactivity in the cerebrospinal fluid (P< 0.001), but not in plasma. The results indicate that CGRP plays a role in the transmission of nociceptive information in the spinal cord of thermally injured rats. Furthermore, our findings suggest that opioids can modulate CGRP-related effects in the spinal cord.

Animals↗
PubMed1997

Differential effects of guanine nucleotides on [125I]-hCGRP(8-37) binding to porcine lung and human neuroblastoma cell membranes.

Calcitonin gene-related peptide (CGRP) mediates its effects by binding to specific receptors which are positively coupled to adenylyl cyclase. CGRP(8-37), a CGRP fragment devoid of the N-terminal region, was shown to be a competitive CGRP receptor antagonist. Only a limited amount of data exists on the usefulness of this ligand in studying CGRP receptors. In the present study, we used [125I]-hCGRP(8-37) to characterize CGRP receptors in porcine lung and human neuroblastoma cell (SK-N-MC) membranes. [125I]-hCGRP(8-37) displayed specific and high affinity binding in both membrane preparations. Displacement studies using [125I]-hCGRP(8-37) and the agonist CGRP revealed the presence of high and low affinity CGRP binding sites in SK-N-MC cell and porcine lung membranes. Addition of guanylimidodiphosphate [Gpp(NH)p] shifted the competition curve to the right and changed the two affinity states of the receptor to a single affinity in SK-N-MC cell membranes. On the other hand, in porcine lung membranes, the whole competition curve was shifted to the right while maintaining the two affinity states. Thus, our data indicate that the new radioligand [125I]-hCGRP(8-37) is a useful tool for characterizing CGRP receptors and their coupling to guanine nucleotide binding proteins.

Animals↗
PubMed2000

Comparison of brimonidine with latanoprost in the adjunctive treatment of glaucoma. ALPHAGAN/XALATAN Study Group.

OBJECTIVE: This study compared brimonidine with latanoprost as adjunctive therapy for the treatment of open-angle glaucoma and ocular hypertension. BACKGROUND: Patients with open-angle glaucoma or ocular hypertension often require >1 medication to achieve control of intraocular pressure (IOP). Both brimonidine and latanoprost effectively lower IOP, but no previously reported clinical trials have directly compared these agents as adjunctive therapy. METHODS: This was a prospective, randomized, investigator-masked, multicenter, parallel-design clinical trial. Forty patients (69 study eyes) with uncontrolled IOP of < or =34 mm Hg while using a topical beta-blocker plus dorzolamide or pilocarpine were randomly assigned to receive either brimonidine 0.2% BID or latanoprost 0.005% QD over 6 months as adjunctive therapy. Tolerability was assessed by reports of adverse events, and efficacy was determined by reduction in IOP from baseline. Clinical success was defined as the achievement of a > or =15% reduction in IOP from baseline. RESULTS: There were no significant between-group differences in any demographic variable. Most patients in each group were white, had open-angle glaucoma, and were being treated with a nonselective beta-blocker and dorzolamide. When brimonidine or latanoprost was used as an adjunctive agent with a beta-blocker and dorzolamide or pilocarpine, the rates of clinical success at month 1 were 85% (17/20 patients) with brimonidine versus 65% (13/20 patients) with latanoprost (P = 0.144). Overall mean IOP reduction at month 1 was 4.60+/-0.62 mm Hg (22.8%; P < 0.001) with brimonidine and 3.43+/-0.62 mm Hg (17.2%; P < 0.001) with latanoprost, with no significant differences between groups (P = 0.219). Among the patients with an inadequate IOP-lowering response (<15% reduction from baseline), the mean IOP reduction was 0.36+/-0.66 mm Hg with latanoprost (n = 7) and 0.50+/-2.18 mm Hg with brimonidine (n = 3). Brimonidine and latanoprost had comparable IOP-lowering efficacy in patients receiving concomitant pilocarpine therapy (mean change in IOP of -4.23 mm Hg vs -3.75 mm Hg, P = 0.173). In patients concurrently treated with dorzolamide, brimonidine produced a mean change in IOP of -5.29 mm Hg, compared with a mean change of -3.21 mm Hg in the latanoprost group (P = 0.159). Both brimonidine and latanoprost were well tolerated. Few adverse events leading to discontinuation were observed with either drug regimen (n = 2 with brimonidine; n = 0 with latanoprost). CONCLUSIONS: Both brimonidine 0.2% BID and latanoprost 0.005% QD were well-tolerated and reduced IOP in most patients when used as third-line adjunctive therapy. However, clinical success was achieved by 17 of 20 patients (85%) who received brimonidine, compared with 13 of 20 patients (65%) who received latanoprost (P = 0.144). These results suggest that brimonidine 0.2% BID may be more reliable than latanoprost 0.005% QD as adjunctive therapy for glaucoma and ocular hypertension.

Aged↗
PubMed2002

Efficacy and safety of immediate anterior chamber paracentesis in the treatment of acute primary angle-closure glaucoma: a pilot study.

OBJECTIVE: To study the safety and effectiveness of immediate anterior chamber paracentesis, combined with antiglaucomatous medications, in the intraocular pressure control and relief of symptoms of acute primary angle-closure glaucoma (PACG). DESIGN: Prospective noncomparative case series. PARTICIPANTS: Eight consecutive patients with their first attack of acute PACG, with intraocular pressure > or =50 mmHg, were recruited into the study. INTERVENTION: On presentation, each patient received topical pilocarpine (4%) and timolol (0.5%), immediate anterior chamber paracentesis, and systemic acetazolamide and mannitol as primary treatment. The intraocular pressures at 15 and 30 minutes, and then at 1, 2, 3, 12, and 24 hours, were documented by applanation tonometry. MAIN OUTCOME MEASURES: Symptoms, visual acuity, intraocular pressure, corneal edema, angle status on gonioscopy, pupillary size, and reaction. RESULTS: Ten eyes of eight patients seen with acute PACG were recruited. The mean intraocular pressure was reduced from 66.6 +/- 9.1 mmHg to 15.1 +/- 3.5 mmHg immediately after paracentesis, and then to 17.1 +/- 7.0 mmHg at 15 minutes, 21.7 +/- 10.2 mmHg at 30 minutes, 22.7 +/- 11.0 mmHg at 1 hour, and 20.1 +/- 14.6 mmHg at 2 hours after paracentesis. The mean intraocular pressure was less than 21 mmHg at 2 hours and beyond. There was instant symptomatic relief for all patients. No complications from the paracentesis were encountered. CONCLUSIONS: From this preliminary study, immediate paracentesis seems to be safe and effective in controlling the intraocular pressure and eliminating symptoms in acute PACG.

Acetazolamide↗