Effect of pupil dilation on intraocular pressure in preterm and term infants.

PURPOSE: To evaluate the effect of pupil dilation on intraocular pressure in preterm and term newborns. METHODS: This prospective study involved 55 eyes of 28 preterm infants and 38 eyes of 20 term infants. The infants were divided into two groups according to their gestational ages at birth as follows: preterm group, <37 weeks and term group, ≥37 weeks. Pupil dilation was attained with tropicamide 0.5% and phenylephrine 2.5%. Intraocular pressure measurements were performed with Icare PRO (Icare Finland Oy, Helsinki, Finland) before and after pupil dilation. A paired t test was used to compare the measurements before and after pupil dilation. RESULTS: The mean intraocular pressure change was -1.04 ± 3.03 mmHg (6.20/-11.40 mmHg) in the preterm group and -0.39 ± 2.81 mmHg (4.60/-9.70 mmHg) in the term group. A statistically significant difference in intraocular pressure was observed only in the preterm group after pupil dilation (p=0.01). CONCLUSION: An unexpected alteration in intraocular pressure in newborns may occur after pupil dilation, especially in preterm infants.

In vitro evaluation of anti-fungal activity of tropicamide against strains of Candida spp. resistant to fluconazole in planktonic and biofilm form.

Candida spp. is considered to be the third or fourth most common cause of bloodstream infections associated with healthcare services in the world. Currently, several strains exhibit resistance to the traditional treatments, making the development of new therapeutic molecules necessary. Drug repositioning is an alternative that can be used to work around problems such as toxicity, cost and time in the development of new drugs. This study aims to evaluate the in vitro antifungal effect of tropicamide, molecule of anticholinergic action, against planktonic cells of Candida spp. and biofilm of C. albicans. Six strains of different Candida species were used to determine the minimum inhibitory concentration (MIC) of tropicamide and fluconazole according to CLSI document M27-A3 and one strain of C. albicans was used to evaluate the activity of tropicamide against biofilms. In concentrations of 64µg/mL, the tropicamide exhibited 50% of inhibitory activity in planktonic cell and in concentrations of 128µg/mL is able to inhibit the formation of C. albicans biofilm. Despite the inhibitory activity shown at the present study, the use of a larger number of strains, as well as in vivo cytotoxicity assays, is necessary to confirm the hypothesis that tropicamide can be used as an adjuvant agent in the treatment of infections by the Candida genus.

Tropicamide 1% mydriatic effect: comparison between spray in closed eyes and eye drops in open eyes.

PURPOSE: The aim of this study was to evaluate by serial measurements, pupil mydriasis produced by topical application of tropicamide 1% using a spray in a closed eye or instillation in an open eye in adult and elderly populations. METHODS: The research was done from February to April of 2011 in the Policlinica Ronaldo Gazolla, located in the Arcos da Lapa Campus of Estacio de Sá University, RJ- Brazil. It was a clinical trial, controlled and randomized, made in a series of 50 patients that were being prepared for ophthalmoscopy examination. They were submitted to eye drop administration of 1% tropicamide in an open eye and to eyelid margin vaporization in a closed eye. The eyes were chosen for the administration of drops or spray according to a pseudo-random numbers table from Excel (2007) before application. The pupil diameter was measured before instillation and after 10, 20, and 30 min in both eyes, with a millimeter ruler. Biostat 5.0 software was used for statistical calculations. RESULTS: Tropicamide 1% was vaporized in a group that presented the following average pupil diameters: 3 mm before the application; 4.16 mm in 10 min; 5 mm in 20 min; and 5.35 mm in 30 min. The group in which tropicamide 1% was instilled presented 2.96 mm of average pupil diameter before the application; 4.22 mm at 10 min; 5.02 mm at 20 min; and 5.44 at 30 min. The two way analysis of variance showed P<0.0001, and the Tukey test performed for comparisons among the groups showed statistical significant differences among all groups except when the measurements were done at the same time. CONCLUSION: The vaporized tropicamide 1% mydriatic effect in closed eyes was clinically equivalent to the instillation effect of eye drop in open eyes. Other mydriatic drugs sprayed in closed eyes may not have the same effect.

Cholinergic autoantibodies from primary Sjögren's syndrome modulate submandibular gland Na+/K+-ATPase activity via prostaglandin E2 and cyclic AMP.

We demonstrate that patients with primary Sjögren's syndrome (pSS) produce functional IgG autoantibodies that interact with the glandular M(3) muscarinic acetylcholine receptors (mAChRs). These autoantibodies act as a partial muscarinic agonist, increasing prostaglandin E(2) (PGE(2)) and cyclic AMP production through modifying Na(+)/K(+)-ATPase activity, but also interfere with the secretory effect of the parasympathetic neurotransmitter. The IgG from patients with pSS has two effects on the submandibular gland. On the one hand, it may act as an inducer of the proinflammatory molecule (PGE(2)) that, in turn, inhibits Na(+)/K(+)-ATPase activity. On the other hand, it plays a role in the pathogenesis of dry mouth, abolishing the Na(+)/K(+)-ATPase inhibition and the net K(+) efflux stimulation of the salivary gland in response to the authentic agonist pilocarpine, decreasing salivary fluid production.

Muscarinic receptor antagonism at the spinal cord level causes inhibitory effects on male rat sexual behavior.

The role of cholinergic neurotransmission in male rat sexual behavior at the brain level has been studied by several researchers. However, little is known about its role at the spinal cord level. In this study, the effects of the intrathecal (IT) administration of the muscarinic receptor antagonist subtypes (MRAs) methoctramine (Meth), tropicamide (Trop) and 4-DAMP on male rat sexual behavior were evaluated during three ejaculatory series. Meth and Trop are preferring antagonists for the M2/M4 receptor subtypes, and 4-DAMP is a preferring antagonist for the M3 receptor subtype. All the MRAs tested noticeably inhibited male rat copulatory behavior, reflected by a reduction in the number of animals engaging in sexual behavior and a gradual decrease in the number of animals able to ejaculate. Significant increases in intromission latency (IL), ejaculation latency (EL) and post-ejaculatory interval (PEI) were observed. The ranking of inhibitory potency in all recorded parameters was Meth>/=4-DAMP>Trop. In theory, the effects of Meth and Trop could be a result of interaction with M2/M4 receptors. However, given that the M2 receptor constitutes the greatest population of muscarinic receptors at all spinal cord sites and given the high affinity for Meth on M2 receptors, the high potency in the inhibitory effects of Meth is indicative of the special role of M2 spinal receptors in the implementation of this behavior. The weaker effects of Trop could be linked to the smaller population of M4 receptors in the spinal cord, but some interaction with M2 receptors is probable. Since some differences in the pattern of inhibitory response between Meth and 4-DAMP were observed in this and a previous study, a possible role for M3 receptors must be considered. The data obtained in this study confirm the facilitating effect of acetylcholine (ACh) at the spinal cord level on male rat sexual behavior through muscarinic mechanisms, with an important influence on ejaculatory processes. These data support the hypothesis of the modulating role of ACh on male rat sexual behavior at the spinal cord level.

Central muscarinic receptor subtypes involved in pilocarpine-induced salivation, hypertension and water intake.

BACKGROUND AND PURPOSE: Recent evidence has suggested that pilocarpine (ACh receptor agonist) injected peripherally may act centrally producing salivation and hypertension. In this study, we investigated the effects of specific M(1) (pirenzepine), M(2)/M(4) (methoctramine), M(1)/M(3) (4-DAMP) and M(4) (tropicamide) muscarinic receptor subtype antagonists injected into the lateral cerebral ventricle (LV) on salivation, water intake and pressor responses to peripheral pilocarpine. EXPERIMENTAL APPROACH: Male Holtzman rats with stainless steel cannulae implanted in the LV were used. Salivation was measured in rats anaesthetized with ketamine (100 mg per kg body weight) and arterial pressure was recorded in unanaesthetized rats. KEY RESULTS: Salivation induced by i.p. pilocarpine (4 micromol per kg body weight) was reduced only by 4-DAMP (25-250 nmol) injected into the LV, not by pirenzepine, methoctramine or tropicamide at the dose of 500 nmol. Pirenzepine (0.1 and 1 nmol) and 4-DAMP (5 and 10 nmol) injected into the LV reduced i.p. pilocarpine-induced water intake, whereas metoctramine (50 nmol) produced nonspecific effects on ingestive behaviours. Injection of pirenzepine (100 nmol) or 4-DAMP (25 and 50 nmol) into the LV reduced i.v. pilocarpine-induced pressor responses. Tropicamide (500 nmol) injected into the LV had no effect on pilocarpine-induced salivation, pressor responses or water intake. CONCLUSIONS AND IMPLICATIONS: The results suggest that central M(3) receptors are involved in peripheral pilocarpine-induced salivation and M(1) receptors in water intake and pressor responses. The involvement of M(3) receptors in water intake and pressor responses is not clear because 4-DAMP blocks both M(1) and M(3) receptors.

The cholinergic system in cyclophosphamide-induced Chagas dilated myocardiopathy in Trypanosoma-cruzi-infected rats: an electrocardiographic study.

Chronic Chagasic Cardiomyopathy (CCC) has been related to the cholinergic system by the neurogenic and autoimmune theories. The neurogenic theory explains cardiomyopathy as a result of post-ganglionic parasympathetic denervation. Cyclophosphamide (CP) facilitates the development of autoimmune disease because of a selective depletion of suppressor T cells. In this study we characterized the phenylephrine-induced vasovagal reflex using selective cholinergic drugs, in two rat models: Trypanosoma cruzi (TC) infected animals and CCC CP-treated rat model. To achieve this goal, 3 week old-90 Sprague Dawley rats were divided into four groups: Control (C), CP, TC and TCCP; TC and TCCP were inoculated with 1000 trypomastigotes/g; CP and TCCP were treated with CP 20 mg/Kg twice a week for five times. After 6 months, the studied animals underwent electrocardiographic (EKG), radiographic (Rx) and histopathological (HP) assesments. The vagal integrity was evaluated by application of phenylephrine (PE) plus tacrine, while the muscarinic cholinergic function was evaluated using selective M1, M2, M3 and M4 muscarinic antagonists. Our data show show that TCCP rats displayed the highest frequency of EKG, Rx and HP disturbances. TC and TCCP rats exhibited a decreased response to: 1) phenylephrine-induced vagal baroreflex bradycardia; 2) methoctramine-, 4-DAMP- and tropicamide-induced tachycardia; 3) methoctramine-induced QRS shortening, and 4) tropicamide-induced QT prolongation. In conclusion, CP facilitates the development of CCC in Trypanosoma cruzi infected rats, by promoting parasympathetic disturbances that appear as consequence of alterations on the muscarinic receptor distribution at different neural integration levels.

Neuronal nitric oxide synthase activity in rat urinary bladder detrusor: participation in M3 and M4 muscarinic receptor function.

1. The aim of this paper was to determine the different signalling cascades involved in contraction of the rat urinary bladder detrusor muscle mediated via muscarinic acetylcholine receptors (muscarinic AChR). Contractile responses, phosphoinositides (IPs) accumulation, nitric oxide synthase (NOS) activity and cyclic GMP (cGMP) production were measured to determine the reactions associated with the effect of cholinergic agonist carbachol. The specific muscarinic AChR subtype antagonists and different inhibitors of the enzymatic pathways involved in muscarinic receptor-dependent activation of NOS and cGMP were tested. 2. Carbachol stimulation of M(3) and M(4) muscarinic AChR increased contractility, IPs accumulation, NOS activity and cGMP production. All of these effects were selectively blunted by 4-DAMP and tropicamide, M(3) and M(4) antagonists respectively. 3. The inhibitors of phospholipase C (PLC), calcium/calmodulin (CaM), neuronal NOS (nNOS) and soluble guanylate cyclase, but not of protein kinase C and endothelial NOS (eNOS), inhibited the carbachol action on detrusor contractility. These inhibitors also attenuated the muscarinic receptor-dependent increase in cGMP and activation of NOS. 4. In addition, sodium nitroprusside and 8-bromo-cGMP, induced negative relaxant effect. 5. The results obtained suggest that carbachol activation of M(3) and M(4) muscarinic AChRs, exerts a contractile effect on rat detrusor that is accompanied by an increased production of cGMP and nNOS activity. The mechanism appears to occur secondarily to stimulation of IPs turnover via PLC activation. This in turn, triggers cascade reactions involving CaM, leading to activation of nNOS and soluble guanylate cyclase. They, in turn, exert a modulator inhibitory cGMP-mediated mechanism limiting the effect of muscarinic AChR stimulation of the bladder.

Estudo comparativo da acomodaçäo residual após instilaçäo de colírios de tropicamida a 1 por cento, ciclopentolato a 1 por cento e associaçäo de tropicamida a 1 por cento + ciclopentolato a 1 por cento / Comparative study of residual accomodation after instillation of the eye drops with 1 per cent tropicamide, 1 per cent cyclopentolate, and association of 1 per cent tropicamide + 1 per cent cyclopentolate

Objetivo: Avaliar a acomodaçäo residual após a instilaçäo de duas drogas ciclopégicas, o ciclopentolato a 1 por cento e a tropicamida a 1 por cento e a associaçäo entre elas. Material e métodos: Selecionamos pacientes de 15 a 25 anos, com íris grau 4 e 5 pela classificaçäo de Seddon e sem nenhum tipo de doença ocular, que procuraram de maneira espontânea o ambulatório de Oftalmologia da Santa Casa de Säo Paulo no período de outubro de 1997 a setembro de 1998. Os 46 pacientes foram submetidos a três exames oftalmológicos completos, em que se testava o potencial de acomodaçäo monocularmente, após a instilaçäo de tropicamida a 1 por cento, com tempo de espera de 20 minutos, ciclopentolato a 1 por cento com tempo de espera de 40 minutos e tropicamida a 1 por cento + ciclopentolato a 1 por cento com intervalo entre as drogas de 5 minutos e com latência de 30 minutos. O intervalo entre os exames era de no mínimo sete dias. Resultados: Näo houve diferença entre os grupos dos emétropes, dos hipermétropes e dos míopes com nenhuma droga instilada (p>0,005). O ciclopentolato a 1 por cento e a associaçäo entre as drogas proporcionaram menor acomodaçäo residual estatisticamente significante, em comparaçäo com a tropicamida a 1 por cento no grupo dos hipermétropes e dos míopes. Conclusäo: O ciclopentolato a 1 por cento e a associaçäo entre as drogas säo seguras para o exame refratométrico estático em pacientes jovens, com íris escura e sem doença ocular, pois proporcionaram uma média da acomodaçäo residual em todos os grupos pesquisados de no máximo 1,21 + ou - 0,7 dioptrias esféricas (DE).