Non-Status Epilepticus female rats show seizure-like behaviors in the chronic phase of Pilocarpine experimental model / Ratas sem Status Epilepticus apresentam comportamento do tipo crise epiléptica na fase crônica do modelo experimental da Pilocarpina

Only few studies have focus on animals that received Pilocarpine (Pilo) and did not develop behavioral status epilepticus (SE) and, whether they may become epileptic in the model's chronic phase. Previews works observed mossy fiber sprouting in the hippocampus of Non-SE (NSE) rats, while others observed spontaneous and recurrent seizures (SRS) 6 - 8 months after animals received Pilo. It is known that neuronal excitability is influenced by female hormones, as well as, the occurrence of SE in castrated and non-castrated female rats. However, it is not known whether females that received Pilo and did not show SE, may have SRS. The aim of this work was to investigate whether castrated and non-castrated female rats that did not show behavioral SE after Pilo, will develop SRS in the following one-year. For that, animals received 360 mg/kg of Pilo and were video monitored for 12 months. SE females from castrated and non-castrated groups became epileptic since the first month after drug injection. Epileptic behaviors were identified watching video monitoring recordings in the fast speed. Castrated and Non castrated NSE animals showed behaviors resembling seizures described by Racine Scale stages 1 - 3. Motor alterations showed by NSE groups could be observed only when recordings were analyzed in slow speed. In addition, behavioral manifestations as, rhythmic head movements, sudden head movements, whole body movements and immobility were also observed in both, SE and NSE groups. We concluded that NSE female rats may have become epileptic. Adding to it, slow speed analysis of motor alterations was essential for the observation of NSE findings, which suggests that possibly many motor alterations have been underestimated in epilepsy experimental research.

Poucos são os estudos com foco em animais que receberam Pilocarpina (Pilo) e não desenvolveram status epilepticus (SE) comportamental e, se os mesmos se tornarão epilépticos na fase crônica do modelo. Autores observaram o brotamento das fibras musgosas no hipocampo de ratos Não-SE (NSE), enquanto outros observaram crises espontâneas e recorrentes (CER) 6 - 8 meses após receberam a droga. A excitabilidade neuronal é influenciada pelos hormônios femininos e, da mesma forma, a ocorrência de SE em ratas castradas e não-castradas. Entretanto, não é sabido se as fêmeas que não apresentam SE terão CER. O objetivo deste trabalho foi investigar se fêmeas castradas e não castradas que não tiveram SE comportamental após a injeção de Pilo desenvolverão CER dentro de um ano. Para isto, os animais receberam 360 mg/kg de Pilo e foram videomonitorados por 12 meses. As fêmeas SE castradas e não-castradas se tornaram epilépticas desde o primeiro mês pós Pilo. O comportamento epiléptico foi identificado assistindo as gravações na velocidade rápida. As fêmeas NSE castradas e não-castradas apresentaram comportamentos similares aos estágios 1 - 3 da Escala de Racine. As alterações motoras nestes grupos (NSE) foram observadas apenas quando as videomonitoração foi analisada na velocidade lenta. Além destas, manifestações comportamentais como movimentos rítmicos da cabeça, movimentos súbitos da cabeça, movimentos de todo o corpo e imobilidade também foram observadas em ambos grupos, SE e NSE. Concluímos que as fêmeas NE podem ter se tornado epilépticas. Adicionado a isto, a análise das alterações motoras na velocidade lenta foi essencial para a observação dos achados das fêmeas NSE, o que sugere que possivelmente muitas alterações motoras têm sido subestimados na pesquisa em epilepsia experimental.

A visão em pseudofácicos com ametropia residual após instilação de pilocarpina a 2% / Pseudophakic Vision with residual ametropia after pilocarpine 2% instillation

Resumo Objetivo: Avaliar modificações de acuidade visual, refração, campo visual e diâmetro pupilar, em pacientes pseudofácicos, após a instilação de pilocarpina a 2%. Métodos: Ensaio clínico, controlado, mascarado e randomizado realizado entre maio de 2015 e setembro de 2016 no Hospital Universitário Gaffrée e Guinle, RJ, Brasil. Quarenta pacientes divididos em 2 grupos foram acompanhados em pós-operatório de facectomia com implante de LIO. No grupo de casos houve aplicação de uma gota de pilocarpina a 2%, no grupo controle, uma gota de lubrificante no olho operado. Foram avaliadas antes e 1 hora após a instilação do colirio: a acuidade visual para longe e perto com e sem correção; a refração; o diâmetro pupilar e o campo visual. Resultados: No grupo de casos, a acuidade visual s/c para longe aumentou de 0,33 para 0,57 (p = 0,0001) e para perto melhorou também, 13 pacientes (59,09%) possuíam acuidade visual de J1 ou J2 antes da instilação e depois o número aumentou para 18 ou 81,81% (p = 0,0054). O diâmetro pupilar reduziu de 2,00mm para 1,85mm (p < 0,0001). Não houve alteração do campo visual central. No grupo controle, não houve variação estatisticamente ou clinicamente significativa de qualquer um dos parâmetros medidos. Conclusão: A administração tópica de uma gota de pilocarpina a 2% melhorou a visão de pacientes pseudofácicos com ametropia residual para longe e para perto. Estudos de dose-efetividade adicionais podem indicar melhores concentrações e posologias para alcançar maiores melhoras de acuidade visual.

Abstract Objective: Evaluate the visual acuity, refraction, visual field changes and pupillary diameter in pseudophakic patients after instillation of 2% pilocarpine eye drops. Methods: Controlled, masked and randomized clinical trial carried out between May, 2015 and September, 2016 at the Gaffrée and Guinle University Hospital, RJ, Brazil. Forty patients, divided into 2 groups, were followed up in the postoperative period of a facectomy with intraocular lens implant. The patients in the group of cases were submitted to a drop of 2% pilocarpine and those of the control group to a drop of lubricant in the operated eye. Before eye drop instillation nd one hour after it, the authors evaluated: visual acuity for distance and near; refraction; pupillary diameter and visual field. Results: In case group visual acuity increased from 0.33 to 0.57 for far (p = 0.0001)and also increased for near, 13 patients (59.09%) had visual acuity of J1 or J2 before instillation and 18 or 81.81% after it (p = 0.0054). The median pupillary diameters raised from 2.00 mms to 1.85 mm(p <0.0001). Central visual fields did not have significant alteration. In the control group, there were no statistically or clinically significant changes in any of the measured parameters. Conclusion: Topical administration of a 2% pilocarpine eye drop was effective to improve pseudophakic patients vision with residual ametropia for far and near. Additional dose-effectiveness studies may indicate better concentrations and dosages to achieve greater improvements in visual acuity.

Salivary stimulation by prolonged release of pilocarpine in sjõgren’ syndrome

Introduction: Prolonged drug delivery in the oral cavity offers many advantages, such as reducing adverse effects. Pilocarpine is an FDA-approved parasympathomimetic drug for the treatment of glandular hypofunction; however, its adverse effects limit its use. Objective: To evaluate the stimulation of salivary flow by the use of pilocarpine-releasing films, as well as their effects on the symptoms of xerostomia and adverse effects in patients with Sjõgren’s syndrome (SS). Materials and methods: Hydroxypropylmethylcellulose (Methocel K4MCR) films were prepared in 1 percent acetic acid and pilocarpine was added under magnetic stirring. The pH and thickness, as well as diffusion uniformity and kinetics of drug release per cm2 were evaluated by spectrophotometry. The films were tested sublingually in 40 patients with Sjõgren’s syndrome for a period of two weeks. Changes in their salivary flow were evaluated by analyzing samples of total saliva. Additionally, patients were screened for symptoms of xerostomia and adverse effects. Results: The films had a pH of 2.91 +/- 0.035, a thickness of 0.06866 +/- 0.00152μm, and a diffusion uniformity of 91 percent per cm2. Use of the films resulted in an increase in salivary flow in both primary and secondary Sjõgren’s syndrome, but this increase was only significant in primary SS. Conclusion: Films showed optimal physicochemical properties for their administration, and proved effective in stimulating salivary flow without causing adverse effects during their administration.

Pupila dilatada fixa (síndrome de Urrets-Zavalia) após ceratoplastia lamelar profunda / Fixed dilated pupil (Urrets-Zavalia syndrome) after deep lamellar keratoplasty

A Síndrome de Urrets-Zavalia apresenta achados oculares bem descritos, porém sua fisiopatologia ainda é incerta. A isquemia iriana é o mecanismo proposto mais comum. Descrevemos dois casos submetidos à ceratoplastia lamelar profunda (CLP) realizadas pelo mesmo cirugião que desenvolveram a síndrome. No primeiro caso, a indicação cirúrgica foi para o tratamento de opacidade corneana e, no segundo, para o de ceratocone. No pós-operatório, ambos os pacientes evoluíram com pupila dilatada fixa que não regrediu totalmente apesar do tratamento administrado.

The Urrets-Zavalia Syndrome presents well described ocular findings, even though its physiopathology is still unsure. Iris ischemia is the most common proposing mechanism. We describe two cases that underwent deep lamellar keratoplasty (DLK) performed by the same surgeon and developed the syndrome. In the first case, the surgical indication was for corneal opacity treatment and, in the second case, for keratoconus treatment. During the post-operatory, both patients developed fixed dilated pupil, which didn't regress completely inspite of the onset treatment.

Effects of milk curd on saliva secretion in healthy volunteer compared to baseline, 2% pilocarpine and equivalent pH adjusted acetic acid solutions.

Background: Dry mouth is a common clinical problem, and different products have been proposed to improve it. In this investigation, the effects of "milk curd" on the amount of saliva secretion were studied. Materials and Methods: A total of 32 patients (aged 20-30) were selected from healthy volunteers. Milk curd concentrations of 0.5, 1, 2 and 4%, and 2% pilocarpine were prepared as drops. The impact of the drugs on the saliva weight was assessed after 1-5 min. To determine the effects of the pH of the milk curd on the amount of saliva secretion, different concentrations of acetic acid were used. Results: At the end of the first minute, the differences between the data for all groups were statistically significant, and the difference between the 2% and 4% milk curd groups was higher than the others (P < 0.0001). The differences in the amount of the saliva secreted at the end of the second minute between the baseline and 4% milk curd groups and between the 0.5% and 4% MC groups were significant (P = 0.006 and P = 0.025, respectively). In total, there was no significant difference between the effect of various pH treatments and the amount of baseline saliva secretion. Conclusion: Milk curd has a significant local impact, and the saliva increase depends on the dose. It seems that this effect is not only related to its acidic taste. As a result, factors other than pH are involved in the effect.

Nestin down-regulation of cortical radial glia is delayed in rats submitted to recurrent status epilepticus during early postnatal life / Atraso no desaparecimento da nestina na glia radial cortical de ratos submetidos a recorrentes status epilepticus durante o desenvolvimento pós-natal precoce

OBJECTIVE: Nestin is temporarily expressed in several tissues during development and it is replaced by other protein types during cell differentiation process. This unique property allows distinguishing between undifferentiated and differentiated cells. This study was delineated to analyze the temporal pattern of nestin expression in cortical radial glial cells of rats during normal development and of rats submitted to recurrent status epilepticus (SE) in early postnatal life (P). METHOD: Experimental rats were submitted to pilocarpine-induced SE on P7-9. The cortical temporal profile of nestin was studied by immunohistochemistry at multiple time points (P9, P10, P12, P16, P30 and P90). RESULTS: We observed delayed nestin down-regulation in experimental rats of P9, P10, P12 and P16 groups. In addition, few radial glial cells were still present only in P21 experimental rats. CONCLUSION: Our results suggested that SE during early postnatal life alters normal maturation during a critical period of brain development.

OBJETIVO: A nestina, temporariamente expressa em diversos tecidos durante o desenvolvimento, é substituída no processo de diferenciação celular, o que permite a distinção entre células diferenciadas e indiferenciadas. O objetivo deste estudo foi verificar o padrão temporal da expressão da nestina nas células da glia radial cortical de ratos durante o desenvolvimento normal e nos ratos submetidos a sucessivos status epilepticus (SE) no periodo pós-natal precoce (P). MÉTODO: Os animais foram submetidos ao SE induzido pela pilocarpina em P7-9. O perfil temporal da nestina foi estudado por imuno-histoquímica em P9, P10, P12, P16, P30 e P90. RESULTADOS: Nos ratos experimentais, observamos atraso no desaparecimento da nestina nos grupos P9, P10, P12 e P16. Ainda, encontramos algumas glias radiais corticais apenas em P21 experimental. CONCLUSÃO: Nossos resultados sugerem que o SE durante o desenvolvimento pós-natal precoce altera o processo de maturação durante um periodo crítico do desenvolvimento encefálico.

A Pharmacologic Pupillary Test in the Diagnosis of Diabetic Autonomic Neuropathy

PURPOSE: To screen for diabetic autonomic neuropathy of the pupil using 0.5% apraclonidine and 0.1% pilocarpine and to evaluate the early diagnostic value of this pharmacologic pupillary test by assessing the relationship between pupillary and cardiovascular autonomic neuropathies. METHODS: A total of 22 diabetic patients were recruited. Baseline pupillary diameter (PD) and the difference in PD between the test eye and the control eye before and after instillation of apraclonidine and pilocarpine were measured. All patients also underwent cardiovascular autonomic function (CAF) testing. RESULTS: Baseline PD in room light correlated with duration of diabetes mellitus (DM, p=0.049) and the presence of DM retinopathy (DMR, p=0.022). Eleven patients (50%) had positive apraclonidine tests, and two patients had positive pilocarpine tests. The patients who had positive pilocarpine tests also had positive apraclonidine tests. Patients who had a positive pupillary test had a significantly higher rate of positive CAF tests (p=0.032). CONCLUSIONS: Pupillary autonomic neuropathy was related to the duration of diabetes and the degree of DMR. There was also a significant correlation between pupillary autonomic neuropathy and cardiovascular autonomic neuropathy (CAN). Also, sympathetic nerve dysfunction occurred prior to parasympathetic dysfunction in this study. A simple pharmacologic pupillary test can help manage complications in diabetic patients because patients with pupillary autonomic dysfunction have an increased risk of CAN.

Effect of oral pilocarpine on post-irradiation xerostomia in head and neck cancer patients: a single-center, single-blind clinical trial.

OBJECTIVE: The authors determined the efficacy and safety of oral pilocarpine tablet in symptomatic relief of post-radiation xerostomia in head and neck cancer patients. MATERIAL AND METHOD: Thirty-three radiation-induced xerostomia patients were enrolled in a single-blind method to receive placebo 1-tablet three times daily in the first month and then oral pilocarpine (5 mg) 1-tablet three times daily for the next three months. Patients were evaluated for subjective symptomatic relief of xerostomia using questionnaires. Objective findings of xerostomia were also evaluated at the same time by two radiation oncologists. RESULTS: All 33 patients had received radiotherapy doses at least 4000 cGy to the parotid glands. Improvement of xerostomia symptoms was observed, with a mean total subjective xerostomia score improvement at the first 4 weeks of oral pilocarpine treatment (p = 0.001), and later throughout the present study. Objective xerostomia score also showed statistically significant improvement at the same time point. Adverse effects of pilocarpine included sweating, nausea, palpitation, and tearing, with sweating as the most common side effect. Adverse effects of placebo included mild headache, nausea, and vomiting. CONCLUSION: Oral pilocarpine was effective and well tolerated in the treatment of radiation-induced xerostomia symptoms.

Efeito neuroprotetor da melatonina e N-acetilserotonina na epileptogênese e no controle de crises em animais submetidos ao modelo da pilocarpina / Neuroprotector effect of melatonin and N-acetilserotonin in the epileptogenesis and in the control of seizures in animals submitted to the pilocarpine model

PURPOSE: The aim of this research was to study the effects of treatment with melatonin and N-acetilserotonin in the development of pilocarpina model of epilepsy in adult male rats. METHODS: Part I - The animals were divided in 4 groups: SALINE - animals that received only saline; SE - animals submitted to status epilepticus (SE); NAS + SE - animals that received pre-treatment with N-acetylserotonin and were submitted to SE and MEL + SE - animals that received pre-treatment with melatonin and were submitted to SE. Part II - The animals were divided in 6 groups: SALINE - animals that received only saline; SE - animals submitted to status epilepticus (SE); PX + SE - animals submitted to pinealectomy and to SE 7 days later; SH + SE - animals submitted to sham-surgery and to SE 7 days later; SE + NAS - animals submitted to SE and treated with N-acetylserotonin (2,5 mg/kg), 30 min, 1 h, 2 h, 4 h, 6 h, 12 h, 24 h, 36 h and 48 h after the SE and SE + MEL - animals submitted to SE and treated with melatonin (2,5 mg/kg), 30 min, 1 h, 2 h, 4 h, 6 h, 12 h, 24 h, 36 h and 48 h after the SE. Following the treatment the animals were continuously video-recorded for 60 days. The behavioral parameters were observed: latency for the SE in minutes, latency for the first spontaneous seizures (ie, duration of the silent period), number of spontaneous seizures during the chronic period and mortality. Five animals per group were perfused for neo-Timm assay. RESULTS: Part I - The animals treated with melatonin and N-acetylserotonin presented an increased of latency for the status epilepticus and decreased number of spontaneous seizures during the chronic period when compared to SE group. The mortality was reduced 100 percent in animals treated with melatonin and theses animals presented a minor mossy fibers sprouting. Part II - The latency for the first spontaneous seizures and mortality were similar in all groups. The animals treated with melatonin presented...

Efecto de la pilocarpina y carbachol intratimpánica en el tinnitus / Effect of intratympanic pilocarpine and carbachol in tinnitus

A 33 de 48 pacientes con hipoacusia sensorioneural, cuya principal molestia era el tinitus, se les colocó en la caja timpánica mediante una aguja de punción lumbar Nº 26, punta de lápiz, a través del cuadrante anterior de la membrana timpánica solución de pilocarpina al 1 por ciento y a los otros 15 pacientes solución isopto de carbachol al 2 por ciento. Ambos grupos fueron seleccionados al azar sin considerar edad, sexo o daño topográfico de la vía acústica. La evaluación de su efecto se hace audiométricamente, después de 30 minutos de la inyección intratimpánica, equiparando el tinnitus antes y después del procedimiento, con el mínimo de intensidad de sonido puro o de banda angosta, que más se asemeje al ruido del paciente. Los resultados fueron positivos, desde la anulación completa a diferentes grados de atenuación del tinnitus, suficiente para comprobarlo con la equiparación audiométrica. Estos casos positivos alcanzan a más de la mitad de ellos. Los resultados serían mejores si se hubieran descartado los casos de hipoacusia por exposición a ruido enviados por las mutuales de seguros por accidentes del trabajo y enfermedades profesionales o los casos de presbiacusia. Estos resultados serían buenos si no fuera por la corta duración del efecto de las drogas que no es mayor que 12 a 72 horas del procedimiento. Luego reaparece el tinnitus en su intensidad original. Los resultados mejores fueron con el uso del carbachol frente a los de la pilocarpina. La sustitución de pilocarpina por carbachol se basó en el razonamiento de que el deterioro de las vías eferentes colinérgicas inhibitorias, que se intentan estimular en el oído interno vía ventana redonda, se dañan primero que las vías aferentes. El uso de la pilocarpina presupone un buen funcionamiento colinérgico, ya que su acción es agonista indirecta anulando las enzimas colinoesterasas

Asymmetrical effects of the unilateral implant of pilocarpine on the preoptic-anterior hypothalamic area on spontaneous ovulation of the adult rat

The effects on ovulation at the next strus after unilaterally implanting pilocarpine in the preoptic-anterior hypothalamic area (POA-AHA) of rats on each day of the estrous cycle were analyzed. Implantation on the left side of POA-AHA on the day of estrus blocked ovulation in all animals, whereas implantation on the right side did not (0/5 vs. 4/4, p<0.05). Implantation on diestrus 1 or 2 on either side of the POA-AHA blocked ovulation. Implatation on the righ side of the POA-AHA at the day of proestrus blocked ovulation (1/6 animals ovulated), while 10/12 with pilocarpine on the left side ovulated (p<0.05).The administration of 3.7 µg of GnRH at 13:00 h o the expected day of proestrus induced ovulation in 36/42 treated animals. In rat with a pilocarpine implant, the injection of estradiol benoznate on diestrus 2 restored ovulation only in those animals with the pilocarpine implant placed in the left side of the POA-AHA, performed on the day of estrus. The results support the previous estatements that in the adult rat POA-AHA, the cholinergic mechanism regulating preovulatory GnRH release, is lateralized. In addition, at the beginning of the estrous phase, the PAO-AHA-cholinergic system needs to remain undisturbed for normal ovulation to take place at the next estrus

Primary argon laser trabeculoplasty vs pilocarpine 2% in primary open angle glaucoma: two years follow-up study.

In a prospective study, the efficacy of argon laser trabeculoplasty (ALT) was evaluated and compared with pilocarpine 2% as primary treatment in newly diagnosed primary open angle glaucoma (POAG). Out of 38 patients with POAG included in this study, one eye each of 36 patients underwent ALT, and one eye each of 26 patients received pilocarpine 2% every 8 hours. The mean pre-treatment IOP was 25.48 +/- 4.13 mmHg in ALT group and 24.47 +/- 3.51 mmHg in the pilocarpine group. The mean post treatment IOP at 2 year follow was 18.2 +/- 2.55 mmHg in ALT group and 18.27 +/- 2.22 mmHg in the pilocarpine group. Post treatment IOP was significantly lower than pre-treatment IOP in both ALT and pilocarpine groups. The post treatment fall in IOP showed no significant difference in ALT versus pilocarpine 2% at various follow up intervals (p > 0.05). This study showed equal efficacy of ALT and pilocarpine 2% as initial therapy of POAG.

A comparative evaluation of pilocarpine 1% and clonidine 0.125% versus timolol 0.5%.

All the presently available antiglaucoma medications have either local or systemic adverse effects. Combinations of drugs are being used not only to increase the effectivity and compliance but also to decrease the incidence and magnitude of side effects. The single dose response of open angle glaucoma eyes to pilocarpine 1%, clonidine 0.125%, a combination of pilocarpine 1% and clonidine 0.125%, and timolol 0.5% was studied in a double blind, masked, cross over study. Over a period of twelve hours the effectivity of the combination of pilocarpine 1% and clonidine 0.125% was significantly more than that of either drug alone and was found to be similar to that of timolol 0.5%. No local or systemic adverse effects were seen.

Pharmacodynamic effects of pilocarpine eye drop enhanced by decreasing its volume of instillation.

Previous studies have proved that as the volume of the drug solution instilled into the eye is decreased, the fraction of the dose absorbed into the ocular tissue is increased and the adverse drug reactions lowered. The present study investigated the acute effects of different drop volumes (10 microliters, 20 microliters, 40 microliters, and 80 microliters) of pilocarpine nitrate (2%) on pupil diameter, heart rate, and adverse reaction profile, in 12 healthy human volunteers. The drop volumes of 10 microliters and 20 microliters produced more miosis and less side effects than 40 microliters and 80 microliters drop volumes. This may be due to more penetration of the drug into the ocular tissue and less drainage into the nasolacrimal system.

Prova de Mapstone em olhos acometidos de glaucoma agudo primário / Mapstone provocative test

Vinte e oito olhos de 28 pacientes portadores de glaucoma agudo primário foram submetidos à prova provocativa de Mapstone. A prova foi negativa em todod sos pacientes estudados e o autor faz consideraçöes a respeito desse teste provocativo, e a respeito dos resultados obtidos na sua amostra

Acción sobre la hidroconductancia del humor acuoso de medicamentos de acción hipotensora / Action of hypotensive drugs on aqueous humor hydroconductance

Con el motivo de acercarnos más al encuentro del medicamento ideal en el tratamiento del glaucoma, investigamos la acción de una dosis única de maleato de timolol al 0,25 % en ambos ojos de 10 personas normales y 10 con glaucoma crónico simple. Igual procedimiento se repitió con la pilocarpina al 2 %. En comparación, el timolol al 0,25 % fue superior a la pilocarpina al 2 %; fundamentalmente la reducción de la rigidez escleral. Por otro lado, los pacientes glaucomatosos respondieron con mayor disminución de la mayoría de los indicadores ante el timolol que ante la pilocarpina

Resposta das glândulas sudoríparas écrinas à estimulaçäo colinérgica em asmáticos

Avaliamos a funçäo do sistema colinérgico, através da resposta das glândulas sudoríparas à estimulaçäo com pilocarpina, em 56 crianças com asma brônquica. Um grupo de pacientes com mucoviscidose (19) e outro de crianças que näo apresentavam doenças respiratórias (19) serviu de controle e foi pareado em relaçäo à idade e sexo. Näo houve diferenças significativas na quantidade de suor nos três grupos, e também näo houve diferença na concentraçäo de sódio no suor entre o grupo de asmáticos e o grupo de crianças sem doenças respiratórias. Estes resultados opöem-se aos resultados de estudos com indivíduos adultos e poderiam sugerir que a respostas aumentada do sistema colinérgico é exclusiva do aparelho respiratório ou que as anormalidades de ordem sistêmica do parassimpático em asmáticos säo adquiridas após a infância