Rat clonidine mydriasis model:Imidazoline receptors are not involved

The clonidine mydriasis model in rats has been widely applied in preclinical research to characterize a -adrenoceptor antagonistic properties of drugs. The present study was undertaken to pharmacologically determine if imidazoline I receptors are also involved in this model system. Sigmoid dose-response curves for pupillary dilation were produced in pentobarbital anesthetized rats by intravenous administration of increasing doses of agonists (guanabenz for a -adrenoceptors, clonidine for both a - adrenoceptors and imidazoline I receptors, and rilmenidine for imidazoline I receptors). Two antagonists (RS 79948 for a -adrenoceptors and efaroxan for imidazoline I receptors) were used to antagonize the mydriasis elicited by those three agonists, with antagonistic potencies calculated. In additional experiments, we examined the effect of the selective imidazoline I receptor antagonist, AGN 192403, on clonidine-induced mydriasis. The results showed that pupillary response curves elicited by guanabenz, clonidine and rilmenidine were competitively antagonized by both RS 79948 (0.03-1 mg/kg) and efaroxan (0.03-1 mg/kg) in a dose-related fashion. The potencies of either antagonist against the three agonists were not significantly different. AGN 192403 (5 mg/kg) did not significantly shift the clonidine mydriasis curve. These results suggest that imidazoline I receptors are not functionally involved in the rat clonidine mydriasis model and support this in vivo system as a useful model for studies of a -adrenoceptors. © 2004 Elsevier B.V. All rights reserved.

α-adrenoceptors do not mediate reflex mydriasis in rabbits

The aim of this study was to identify receptors that mediate reflex mydriasis in pentobarbital-anesthetized rabbits, in which the cervical sympathetic nerve was sectioned unilaterally. Voltage-response curves of pupillary dilation were generated bilaterally by stimulation of the sciatic nerve. Evoked mydriatic responses were mediated mainly by efferent parasympathetic innervation, and, to a lesser extent, by sympathetic innervation. The a-adrenergic antagonist, phenoxybenzamine (0.3 mg/kg, intravenously (i.v.)), antagonized mydriasis of the neurally intact eye, but not that on the sympathectomized side. The a- adrenergic antagonist, RS 79948 (0.3 mg/kg, i.v.), potentiated mydriasis of the normal eye, but was without either a potentiating or inhibitory effect on the mydriasis of the sympathectomized eye. In addition, the dopamine-receptor antagonist, haloperidol (1 mg/kg, i.v.), inhibited evoked mydriasis of the sympathectomized eye. These results suggest that, unlike some other species (cats and rats), a-adrenoceptors do not mediate reflex mydriasis elicited by sciatic-nerve stimulation in the rabbit, and support the previous finding in humans that dopamine receptors may mediate this response.

Studies of alpha-adrenoceptor antagonists on sympathetic mydriasis in rabbits

This study was undertaken to identify the alpha-adrenergic receptor type responsible for sympathetically evoked mydriasis in pentobarbital-anesthetized rabbits. Frequency-response curves of pupillary dilation were generated by stimulation of the preganglionic cervical sympathetic nerve (1-64 Hz). Evoked mydriatic responses were inhibited by systemic administration of nonselective alpha-adrenergic antagonists, phentolamine (0.3-10 mg/kg) and phenoxybenzamine (0.03-0.3 mg/kg), as well as the selective alpha(1)-adrenergic antagonist, prazosin (0.1-1 mg/kg). The alpha(2)-adrenergic antagonist, RS 79948 (0.3 mg/kg, i.v.) was without inhibitory effect, but potentiated the mydriatic response. In addition, the selective alpha(1A)-adrenoceptor antagonist, 5-methylurapidil (0.1-1 mg/kg, i.v.), antagonized the elicited mydriasis in a dose-dependent fashion. Unlike previous observations that prazosin does not block the adrenoceptor in rabbit iris dilator muscle, our results suggest that prazosin is effective in inhibiting neuronally elicited mydriasis in this species, and that alpha(1A)-adrenoceptors appear to mediate the response.

Histamine H3 receptor-mediated inhibition of sympathetically evoked mydriasis in rats

This study was designed to determine if the histamine H3 receptor agonist R-alpha-methylhistamine would play a role in modulation of sympathetically evoked mydriasis in anesthetized rats, and if so, to ascertain the specific receptor subtype(s) involved. Reproducible frequency-response curves of pupillary dilation were generated by stimulation of the cervical preganglionic sympathetic nerve (1-32 Hz). Systemic administration of R-alpha-methylhistamine (0.3-3.0 mg kg(-1)) produced a dose-related inhibition of the evoked mydriasis. The greatest inhibition was seen at lower frequency levels, with about 43% depression observed at 2 Hz. The specific histamine H3 receptor antagonist, clobenpropit (3.0 mg kg(-1), i.v.), blocked the inhibitory effect of R-alpha-methylhistamine, whereas neither the histamine H2 receptor antagonist, cimetidine (5.0 mg kg(-1), i.v.), nor the histamine H1 receptor antagonist, chlorpheniramine (0.5 mg kg(-1), i.v.), was effective. The histamine H2 receptor agonist, dimaprit (10 mg kg(-1), i.v.), was also without effect on the evoked mydriasis. R-alpha-methylhistamine (3.0 mg kg(-1)) did not inhibit phenylephrine-induced mydriasis. These results support the conclusion that R-alpha-methylhistamine produces inhibition of sympathetically evoked mydriasis via histamine H3 receptor stimulation, presumably by an action on presynaptic histamine H3 receptors.

Decision fusion from parts and samples for robust iris recognition

Fusion techniques can be used in biometrics to achieve higher accuracy. When biometric systems are in operation and the threat level changes, controlling the trade-off between detection error rates can reduce the impact of an attack. In a fused system, varying a single threshold does not allow this to be achieved, but systematic adjustment of a set of parameters does. In this paper, fused decisions from a multi-part, multi-sample sequential architecture are investigated for that purpose in an iris recognition system. A specific implementation of the multi-part architecture is proposed and the effect of the number of parts and samples in the resultant detection error rate is analysed. The effectiveness of the proposed architecture is then evaluated under two specific cases of obfuscation attack: miosis and mydriasis. Results show that robustness to such obfuscation attacks is achieved, since lower error rates than in the case of the non-fused base system are obtained.

Pseudophakic retinal detachment

Pseudophakic retinal detachment is a rare, but potentially serious, complication of cataract surgery. The incidence of pseudophakic retinal detachment following current surgical techniques of cataract extraction, including extracapsular cataract extraction by nuclear expression and phacoemulsification, is lower than that found after intracapsular cataract extraction. The risk of pseudophakic retinal detachment appears to be increased in myopic patients, in those patients in whom vitreous loss had occurred at the time of cataract surgery, and in patients undergoing Nd:YAG posterior capsulotomy. Most cases present to the clinician when the macula is already detached and the central vision is affected. When evaluating patients with pseudophakic retinal detachment, the fundal view is often impaired by anterior or posterior capsular opacification, reflections related to the intraocular lens, or poor mydriasis. Scleral buckling, pneumatic retinopexy, and primary pars plana vitrectomy, with or without combined scleral buckling, are the surgical techniques used to treat pseudophakic retinal detachment. Anatomical success rates are high after vitreo-retinal surgery for pseudophakic retinal detachment, although a smaller proportion of patients recover good vision following surgery. © 2003 Elsevier Inc. All rights reserved.

Pharmacological studies of 8-OH-DPAT-induced pupillary dilation in anesthetized rats

Serotonin (5-HT) receptor agonists have been reported to produce mydriasis in mice, and miosis in rabbits and humans. However, the underlying mechanisms for this action are unclear. This study was undertaken in an attempt to explore the mechanism by which 5-HT receptors are involved in the modulation of pupillary size in pentobarbital-anesthetized rats. Intravenous administration of the 5-HT receptor agonist, (2R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT; 0.003-3 mg/kg), elicited dose-dependent pupillary dilation, which was not affected by section of the preganglionic cervical sympathetic nerve. 8-OH-DPAT-elicited mydriatic responses were attenuated by the selective 5-HT receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2- pyridinylcyclohexanecarboxamide maleate (WAY 100635; 0.3-1 mg/kg, i.v.), as well as by the selective a -adrenoceptor antagonist, (8aR,12aS,13aS)-5,8,8a,9,10,11,12,12a,13,13a-dechydro-3-methoxy-12- (ethylsulfonyl)-6H-isoquino[2,1-g][1,6]naphthyridine hydrochloride (RS 79948; 0.3 mg/kg, i.v.), but not by the selective a -adrenoceptor antagonist, prazosin (0.3 mg/kg, i.v.). Mydriatic responses elicited by the a -adrenoceptor agonist, guanabenz (0.003-0.3 mg/kg, i.v.), were not antagonized by WAY 100635 (0.3-1 mg/kg, i.v.). To determine whether central nervous system (CNS) 5-HT receptors, like a -adrenoceptors, are involved in reflex mydriasis, voltage response curves of pupillary dilation were constructed by stimulation of the sciatic nerve in anesthetized rats. WAY 100635 (1 mg/kg, i.v.) did not antagonize the evoked reflex mydriasis, which, however, was blocked by RS 79948 (0.3 mg/kg, i.v.). Taken together, these results suggest that 8-OH-DPAT produces pupillary dilation in anesthetized rats by stimulating CNS 5-HT receptors, which in turn trigger the release of norepinephrine, presumably from the locus coeruleus. The latter reduces parasympathetic neuronal tone to the iris sphincter muscle by stimulation of postsynaptic a - adrenoceptors within the Edinger-Westphal nucleus. Unlike a - adrenoceptors, 5-HT receptors in the CNS do not mediate reflex mydriasis evoked by sciatic nerve stimulation. © 2004 Elsevier B.V. All rights reserved.

Functional characterization of alpha-adrenoceptors mediating pupillary dilation in rats

Previously, we reported that the alpha(1A)-adrenoceptor, but not the alpha(1D)-adrenoceptor, mediates pupillary dilation elicited by sympathetic nerve stimulation in rats. This study was undertaken to further characterize the alpha-adrenoceptor subtypes mediating pupillary dilation in response to both neural and agonist activation. Pupillary dilator response curves were generated by intravenous injection of norepinephrine in pentobarbital-anesthetized rats. Involvement of alpha(1)-adrenoceptors was established as mydriatic responses were inhibited by systemic administration of nonselective alpha-adrenoceptor antagonists, phentolamine (0.3-3 mg/kg) and phenoxybenzamine (0.03-0.3 mg/kg), as well as by the selective alpha(1)-adrenoceptor antagonist, prazosin (0.3 mg/kg). The alpha(2)-adrenoceptor antagonist, rauwolscine (0.5 mg/kg), was without antagonistic effects. alpha(1A)-Adrenoceptor selective antagonists, 2-([2,6-dimethoxyphenoxyethyl]aminomethyl)-1,4-benzodioxane (WB-4101; 0.1-1 mg/kg) and 5-methylurapidil (0.1-1 mg/kg), the alpha(1B)-adrenoceptor selective antagonist, 4-amino-2-[4-[1-(benzyloxycarbonyl)-2(S)- [[(1,1-dimethylethyl)amino]carbonyl]-piperazinyl]-6,7-dimethoxyquinazoline (L-765314; 0.3-1 mg/kg), as well as the alpha(1D)-adrenoceptor selective antagonist, 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione (BMY-7378; 1 mg/kg), were used to delineate the adrenoceptor subtypes involved. Mydriatic responses to norepinephrine were significantly antagonized by intravenous administration of both WB-4101 and 5-methylurapidil, but neither by L-765314 nor by BMY-7378. L-765314 (0.3-3 mg/kg, i.v.) was also ineffective in inhibiting the mydriasis evoked by cervical sympathetic nerve stimulation. These results suggest that alpha(1B)-adrenoceptors do not mediate sympathetic mydriasis in rats, and that the alpha(1A)-adrenoceptor is the exclusive subtype mediating mydriatic responses in this species.

alpha(1A)-adrenoceptors mediate sympathetically evoked pupillary dilation in rats

Evidence suggests that in some species (cats, rabbits, and possibly humans) alpha-adrenoceptors in the iris dilator muscle are "atypical" in that they cannot be readily classified by conventional criteria. This study was undertaken in an attempt to characterize the alpha-adrenoceptor subtype(s) mediating sympathetically elicited mydriasis in rats. Frequency-response pupillary dilator curves were generated by stimulation of the preganglionic cervical sympathetic nerve (1-32 Hz) in pentobarbital-anesthetized rats. Evoked responses were inhibited by systemic administration of nonselective alpha-adrenergic antagonists, phentolamine (0.3-10 mg/kg) and phenoxybenzamine (0.03-1 mg/kg). The selective alpha(1)-adrenergic antagonist, prazosin (0.01-1 mg/kg), also was effective, although alpha(2)-adrenergic antagonism with rauwolscine (0.1-1 mg/kg) was not. alpha(1A)-Adrenoceptor-selective antagonists, 2-([2,6-dimethoxyphenoxyethyl]aminomethyl)-1,4-benzodioxane (WB-4101; 0.1-1 mg/kg) and 5-methylurapidil (0.1-1 mg/kg), as well as the alpha(1D)-adrenoceptor-selective antagonist 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione (BMY-7378; 1-3 mg/kg), were used to determine the subtype(s) involved. Evoked mydriasis was significantly antagonized by both WB-4101 and 5-methylurapidil but not by BMY-7378. These results suggest that, unlike some other species, adrenoceptors in the rat iris dilator mediating neurogenic mydriasis are "typical" and, in addition, can be characterized as being primarily of the alpha(1A)-adrenoceptor subtype.

Corneal graft survival after therapeutic keratoplasty for Acanthamoeba keratitis

Purpose: To describe corneal graft survival and visual outcome after therapeutic penetrating keratoplasty in patients with Acanthamoeba keratitis (AK) that is unresponsive to clinical treatment. Methods: Retrospective study. Thirty-two patients with AK who underwent therapeutic penetrating keratoplasty (tPK) from August 1996 to August 2005 were included. Data relating to clinical features, visual acuity, surgical technique, graft survival and complications were collected. Graft survival was evaluated by the Kaplan-Meier method and comparisons were performed using the Log-rank test. Results: Most patients (62.5%) were female. Mean age [+/- standard deviation (SD)] was 35 (+/- 13) years (range 15-68 years). All patients were contact lens wearers. Eighteen patients (56%) presented paralytic mydriasis and glaucoma during the treatment. Thirteen patients (40%) developed glaucoma after surgery; eight of them (61%) required a second PK because of graft failure. Of the 32 keratoplasty eyes, 56.2% presented graft failure at any follow-up point. Forty-five per cent of graft failures occurred before the 12 month follow-up, so 55% remained clear in the first year after surgery. Twelve patients underwent a second PK; seven of them failed and 45% were clear at 1 year. Two patients presented graft recurrence of amoebic infection. There was no significant difference in graft survival when eyes with or without mydriasis were compared (P = 0.40). Eyes with glaucoma presented a significantly shorter graft survival (P = 0.01). Conclusion: Penetrating keratoplasty is a treatment option for eyes that are unresponsive to clinical treatment infections. However, graft survival is poor; postoperative glaucoma is frequent and is associated with shorter graft survival.

Fatores genéticos e não genéticos em formas avançadas de Retinopatia Diabética em pacientes com Diabete Melito tipo 2

Introdução: A retinopatia diabética (RD) é a principal causa de novos casos de cegueira entre norte-americanos em idade produtiva. Existe uma associação entre RD e as outras complicações microvasculares do diabete melito. A associação da RD com a fase inicial da nefropatia, a microalbuminúria, não está esclarecida em pacientes com diabete melito (DM) tipo 2. Polimorfismos de genes (ENNP1; FABP2) relacionados à resistência insulínica, entre outros, poderiam estar associados à RD. Objetivo: O objetivo deste estudo foi avaliar fatores genéticos e não genéticos associados à RD avançada em pacientes com DM tipo 2. Métodos: Neste estudo caso-controle foram incluídos pacientes DM tipo 2 submetidos à avaliação clínica, laboratorial e oftalmológica. Foi realizada oftalmoscopia binocular indireta sob midríase e obtidas retinografias coloridas em 7 campos padronizados. Foram classificados como casos os pacientes portadores de RD avançada (formas graves de RD não proliferativa e RD proliferativa) e como controles os pacientes sem RD avançada (fundoscopia normal, e outras formas de RD). Foram estudados os polimorfismos K121Q do gene ENNP1 e A54T do gene FABP2. Na análise estatística foram utilizados testes paramétricos e não paramétricos conforme indicado. Foi realizada análise de regressão logística múltipla para avaliar fatores associados à RD avançada. O nível de significância adotado foi de 0,05%. Resultados: Foram avaliados 240 pacientes com DM tipo 2 com 60,6 ± 8,4 anos de idade e duração conhecida de DM de 14,4 ± 8,4 anos. Destes, 67 pacientes (27,9%) apresentavam RD avançada. Os pacientes com RD avançada apresentaram maior duração conhecida de DM (18,1 ± 8,1 vs. 12,9 ± 8,2 anos; P< 0,001), menor índice de massa corporal (IMC) (27,5 ± 4,2 vs. 29,0 ± 9,6 kg/m2; P= 0,019), além de uso de insulina mais freqüente (70,8% vs 35,3%; P< 0,001) e presença de nefropatia diabética (81,1% vs 34,8%; P< 0,001) quando comparados com os pacientes sem RD avançada. Na avaliação laboratorial os pacientes com RD avançada apresentaram valores mais elevados de creatinina sérica [1,4 (0,6 -13,6) vs 0,8 (0,5-17,9) mg/dl; P<0,001] e de albuminúria [135,0 (3,6-1816,0) vs 11,3 (1,5-5105,0) μg/min; P<0,001] quando comparados com pacientes sem RD avançada. A distribuição dos genótipos dos polimorfismos do ENNP1 e FABP2 não foi diferente entre os grupos. A análise de regressão logística múltipla demonstrou que a presença de nefropatia (OR=6,59; IC95%: 3,01-14,41; P<0,001) e o uso de insulina (OR=3,47; IC95%: 1,60- 7,50; P=0,002) foram os fatores associados à RD avançada, ajustados para a duração de DM, presença de hipertensão arterial, glicohemoglobina e IMC. Quando na análise foram incluídos apenas pacientes normoalbuminúricos e microalbuminúricos, a microalbuminúria (OR=3,8; IC95%: 1,38-10,47; P=0,010), o uso de insulina (OR=5,04; IC95%: 1,67-15,21; P=0,004), a duração do DM (OR=1,06 IC95%: 1,00-1,13; P=0,048) e a glicohemoglobina (OR=1,35; IC95%: 1,02-1,79; P=0,034) foram os fatores associados à RD avançada, ajustados para a presença de hipertensão arterial e IMC. Conclusão: Pacientes com DM tipo 2 portadores de formas avançadas de RD apresentam mais freqüentemente envolvimento renal pelo DM, incluindo o estágio de microalbuminúria. Uma avaliação renal com medida de albuminúria dever ser incorporada como avaliação de rotina nestes pacientes.

Effects of nitrous oxide on IOP and pupillary diameter in dogs anesthetized with varying concentrations of desflurane

Objective The aim of the present study was to evaluate the effects of nitrous oxide on TOP and pupillary diameter (PD) of dogs anesthetized with varying desflurane concentrations.Animals studied Twenty adult Mongrel dogs were used.Methods They were anesthetized with propofol (10 mg/kg, IV) and maintained with varying concentrations of desflurane (1.6, 1.4, and 1.2 MAC diluted in 100% oxygen (G1) or in 70% nitrous oxide and 30% oxygen (G2) (30 mL/kg/min). TOP was measured by applanation tonometry and horizontal PD was taken with a caliper adjacent to the cornea. Mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), and end-tidal CO, (etCO(2)) were also measured. All parameters were measured at TO, T30, T45, and T60 time points. One-way repeated measures ANOVA and the t-test were used to assess statistical differences (P < 0.05).Results T30, T45, and T60 TOP measures were Within normal limits for both groups and TOP did not differ between groups at any time. There was a significant decrease in PD in G I between TO and T30, T45 and T60, and also between T30 and T60. PD did not differ between groups. All vital parameters were within normal limits throughout anesthesia.Conclusions Administration of nitrous oxide with desflurane results in maintenance of normal TOP and prevents a decrease in horizontal PD during anesthesia. Therefore, this may be a suitable protocol in dogs undergoing intraocular surgeries that require mydriasis and maintenance of normal TOP.

Síndrome de Horner na infância: relato de caso

O intuito deste é apresentar um caso raro de síndrome de Horner na infância. Trata-se de uma criança do sexo masculino, com idade de 2 anos e 1 mês, que apresentava desde o nascimento ptose palpebral, miose e anidrose da hemiface esquerda. A instilação de fenilefrina 2,5% provocou midríase, com pupilas isocóricas, confirmando o diagnóstico. A história e o exame clínico auxiliam a localizar o nível da lesão e a estabelecer a etiologia do quadro.

Clinical and electrocardiographic evaluation during experimental toad poisoning in dogs

Accidents involving toad poisoning are frequent and dogs are the most common victims; they become poisoned by biting or ingesting a toad. When released in the organism, the venom is absorbed by both the oral mucosa and the digestive tract, initiating its toxic action. The aim of this work was to evaluate the clinical and electrocardiographic aspects of dogs subjected to experimental toad poisoning, as well as their response to treatment with propranolol. Twenty dogs were divided into two groups, a control group (n = 5) and a poisoned group (n = 15). After general anesthesia, the control group received a placebo, while the poisoned group received a venom aliquot through an orogastric tube. Results were tested through multivariate analysis (p < 0.05). The animals in the poisoned group had gastrointestinal symptoms including emesis, intense salivation, hyperemic or congested oral mucosa and pasty diarrhea. Non-responsive mydriasis, nystagmus, depression, stupor, tachypnea, opisthotonus and ataxia were also manifested by 100% of the poisoned animals. Affected dogs had an increase in blood pressure, statistically significant throughout study. Five poisoned animals developed ventricular tachycardia and were treated with propranolol (0.5 mg/kg IV). All propranolol-treated animals returned to normal sinus rhythm, which evidences the efficacy of this drug to treat ventricular arrhythmias caused by toad venom.

Kinetics of venom and antivenom serum levels, clinical evaluation and therapeutic effectiveness in dogs inoculated with Crotalus durissus terrificus venom

This work evaluated the clinical and therapeutic aspects as well as serum levels of venom and antivenom IgG by enzyme-linked immunosorbent assay (ELISA) in experimental envenomation of dogs with Crotalus durissus terrificus venom. Twenty-eight mixed breed adult dogs were divided into four groups of seven animals each, Group I: only venom; Group II, venom + 50 ml of anti-bothropic-crotalic serum (50mg) + fluid therapy; Group III, venom + 50 ml of anti-bothropic-crotalic serum + fluid therapy + urine alkalination; Group IV, 50 ml of anti-bothropic-crotalic serum. The lyophilized venom of Crotalus durissus terrificus was reconstituted in saline solution and subcutaneously inoculated at the dose of 1mg/kg body weight. The dogs presented clinical signs of local pain, weakness, mandibular ptosis, mydriasis, emesis and salivation. The venom levels detected by ELISA ranged from 0 to 90ng/ml, according to the severity of the clinical signs. Serum antivenom ranged from 0 to 3ug/ml and was detected for up to 138h after treatment. ELISA results showed the effectiveness of the serum therapy for the venom neutralization.