Evaluation of the anticonvulsant and neuroprotective effect of intracerebral administration of growth hormone in rats / Evaluación del efecto anticonvulsivante y neuroprotector de la administración intracerebral de la hormona de crecimiento en ratas

Introduction The growth hormone (GH) has been reported as a crucial neuronal survival factor in the hippocampus against insults of diverse nature. Status epilepticus (SE) is a prolonged seizure that produces extensive neuronal cell death. The goal of this study was to evaluate the effect of intracerebroventricular administration of GH on seizure severity and SE-induced hippocampal neurodegeneration. Methodology Adult male rats were implanted with a guide cannula in the left ventricle and different amounts of GH (70, 120 or 220 ng/3 μl) were microinjected for 5 days; artificial cerebrospinal fluid was used as the vehicle. Seizures were induced by the lithium–pilocarpine model (3 mEq/kg LiCl and 30 mg/kg pilocarpine hydrochloride) one day after the last GH administration. Neuronal injury was assessed by Fluoro-Jade B (F-JB) staining. Results Rats injected with 120 ng of GH did not had SE after 30 mg/kg pilocarpine, they required a higher number of pilocarpine injections to develop SE than the rats pretreated with the vehicle, 70 ng or 220 ng GH. Prefrontal and parietal cortex EEG recordings confirmed that latency to generalized seizures and SE was also significantly higher in the 120 ng group when compared with all the experimental groups. FJ-B positive cells were detected in the hippocampus after SE in all rats, and no significant differences in the number of F-JB cells in the CA1 area and the hilus was observed between experimental groups. Conclusion Our results indicate that, although GH has an anticonvulsive effect in the lithium–pilocarpine model of SE, it does not exert hippocampal neuroprotection after SE. (AU)

Introducción La hormona de crecimiento (HC) es un factor que favorece la supervivencia neuronal en el hipocampo ante agresiones de diversa naturaleza. El status epilepticus (SE) es un tipo de crisis epiléptica de larga duración que produce muerte neuronal. El objetivo de este estudio fue evaluar el efecto de la administración intracerebroventricular de HC en la severidad de las convulsiones y la neurodegeneración hipocampal debida al SE. Metodología A ratas macho adultas se les implantó una cánula guía en el ventrículo lateral izquierdo y se les microinyectaron diferentes cantidades de HC (70, 120 o 220 ng/3 μl) durante 5 días; como vehículo se inyectó líquido cefalorraquídeo artificial. Las convulsiones se generaron con el modelo de litio-pilocarpina (3 mEq/kg LiCl y 30 mg/kg clorhidrato pilocarpina) un día después de la última inyección de HC. La neurodegeneración se identificó con la tinción de Fluoro-Jade B (F-JB). Resultados Las ratas a las que se les inyectaron 120 ng de HC requirieron 2 o 3 inyecciones de pilocarpina para desarrollar SE, en comparación con el resto de los grupos experimentales que requirieron solo una aplicación del convulsivante. Los registros EEG de la corteza prefrontal y parietal confirmaron que la latencia a las crisis generalizadas y al SE fue mayor en dicho grupo experimental. Todas las ratas con SE presentaron células positivas al FJ-B en el área CA1 e hilus del hipocampo, y no se identificaron diferencias entre los tratamientos. Conclusión Nuestros resultados muestran que, aunque la HC tiene un efecto anticonvulsivante, una vez que se ha desarrollado el SE no promueve neuroprotección en el hipocampo. (AU)

Evaluation of the anticonvulsant and neuroprotective effect of intracerebral administration of growth hormone in rats / Evaluación del efecto anticonvulsivante y neuroprotector de la administración intracerebral de la hormona de crecimiento en ratas

Introduction The growth hormone (GH) has been reported as a crucial neuronal survival factor in the hippocampus against insults of diverse nature. Status epilepticus (SE) is a prolonged seizure that produces extensive neuronal cell death. The goal of this study was to evaluate the effect of intracerebroventricular administration of GH on seizure severity and SE-induced hippocampal neurodegeneration. Methodology Adult male rats were implanted with a guide cannula in the left ventricle and different amounts of GH (70, 120 or 220 ng/3 μl) were microinjected for 5 days; artificial cerebrospinal fluid was used as the vehicle. Seizures were induced by the lithium–pilocarpine model (3 mEq/kg LiCl and 30 mg/kg pilocarpine hydrochloride) one day after the last GH administration. Neuronal injury was assessed by Fluoro-Jade B (F-JB) staining. Results Rats injected with 120 ng of GH did not had SE after 30 mg/kg pilocarpine, they required a higher number of pilocarpine injections to develop SE than the rats pretreated with the vehicle, 70 ng or 220 ng GH. Prefrontal and parietal cortex EEG recordings confirmed that latency to generalized seizures and SE was also significantly higher in the 120 ng group when compared with all the experimental groups. FJ-B positive cells were detected in the hippocampus after SE in all rats, and no significant differences in the number of F-JB cells in the CA1 area and the hilus was observed between experimental groups. Conclusion Our results indicate that, although GH has an anticonvulsive effect in the lithium–pilocarpine model of SE, it does not exert hippocampal neuroprotection after SE. (AU)

Introducción La hormona de crecimiento (HC) es un factor que favorece la supervivencia neuronal en el hipocampo ante agresiones de diversa naturaleza. El status epilepticus (SE) es un tipo de crisis epiléptica de larga duración que produce muerte neuronal. El objetivo de este estudio fue evaluar el efecto de la administración intracerebroventricular de HC en la severidad de las convulsiones y la neurodegeneración hipocampal debida al SE. Metodología A ratas macho adultas se les implantó una cánula guía en el ventrículo lateral izquierdo y se les microinyectaron diferentes cantidades de HC (70, 120 o 220 ng/3 μl) durante 5 días; como vehículo se inyectó líquido cefalorraquídeo artificial. Las convulsiones se generaron con el modelo de litio-pilocarpina (3 mEq/kg LiCl y 30 mg/kg clorhidrato pilocarpina) un día después de la última inyección de HC. La neurodegeneración se identificó con la tinción de Fluoro-Jade B (F-JB). Resultados Las ratas a las que se les inyectaron 120 ng de HC requirieron 2 o 3 inyecciones de pilocarpina para desarrollar SE, en comparación con el resto de los grupos experimentales que requirieron solo una aplicación del convulsivante. Los registros EEG de la corteza prefrontal y parietal confirmaron que la latencia a las crisis generalizadas y al SE fue mayor en dicho grupo experimental. Todas las ratas con SE presentaron células positivas al FJ-B en el área CA1 e hilus del hipocampo, y no se identificaron diferencias entre los tratamientos. Conclusión Nuestros resultados muestran que, aunque la HC tiene un efecto anticonvulsivante, una vez que se ha desarrollado el SE no promueve neuroprotección en el hipocampo. (AU)

Evaluation of the anticonvulsant and neuroprotective effect of intracerebral administration of growth hormone in rats.

INTRODUCTION: The growth hormone (GH) has been reported as a crucial neuronal survival factor in the hippocampus against insults of diverse nature. Status epilepticus (SE) is a prolonged seizure that produces extensive neuronal cell death. The goal of this study was to evaluate the effect of intracerebroventricular administration of GH on seizure severity and SE-induced hippocampal neurodegeneration. METHODOLOGY: Adult male rats were implanted with a guide cannula in the left ventricle and different amounts of GH (70, 120 or 220ng/3µl) were microinjected for 5 days; artificial cerebrospinal fluid was used as the vehicle. Seizures were induced by the lithium-pilocarpine model (3mEq/kg LiCl and 30mg/kg pilocarpine hydrochloride) one day after the last GH administration. Neuronal injury was assessed by Fluoro-Jade B (F-JB) staining. RESULTS: Rats injected with 120ng of GH did not had SE after 30mg/kg pilocarpine, they required a higher number of pilocarpine injections to develop SE than the rats pretreated with the vehicle, 70ng or 220ng GH. Prefrontal and parietal cortex EEG recordings confirmed that latency to generalized seizures and SE was also significantly higher in the 120ng group when compared with all the experimental groups. FJ-B positive cells were detected in the hippocampus after SE in all rats, and no significant differences in the number of F-JB cells in the CA1 area and the hilus was observed between experimental groups. CONCLUSION: Our results indicate that, although GH has an anticonvulsive effect in the lithium-pilocarpine model of SE, it does not exert hippocampal neuroprotection after SE.

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.

Non-Status Epilepticus female rats show seizure-like behaviors in the chronic phase of Pilocarpine experimental model

Abstract 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 models 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.

Resumo 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.

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

Abstract 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.

Resumo 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.

Oral pilocarpine for the treatment of dry eye in patients with Sjögren's syndrome / Pilocarpina oral no tratamento do olho seco de pacientes com síndrome de Sjögren

ABSTRACT Purpose: To evaluate the efficacy of oral pilocarpine (20 mg daily) for the treatment of dry eye in patients with Sjogren's Syndrome. The frequency of side effects reported during the treatment was also investigated. Methods: In this placebo-controlled crossover study, 32 patients with Sjögren's syndrome were enrolled to receive either oral pilocarpine or placebo for 10 weeks. Following a 2-week washout period, the treatment was inverted for each patient for the same duration. Assessments included the quality of life National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25), dry eye specific questionnaire Ocular Surface Disease Index, non-invasive breakup time, invasive breakup time with fluorescein, corneal and conjunctival staining patterns with the use of fluorescein and rose bengal staining, Schirmer's test, and tear ferning test. Results: According to the NEI-VFQ-25, there was statistically significant improvement in the quality of life following oral pilocarpine. Similar results were observed for ocular discomfort, as determined by the Ocular Surface Disease Index. All clinical tests showed favorable and statistically significant results following the use of oral pilocarpine. Regarding the analysis of tear samples, there was an improvement in the quality of tear film. This was evidenced by the modification of the patterns observed in the tear ferning test. Side effects were reported by 96.8% and 56.2% of the patients who received pilocarpine and placebo, respectively. Sweating was the most frequently reported side effect (67.74% versus 11.11%, respectively). Conclusions: Although the treatment was associated with a high frequency of side effects, oral pilocarpine (20 mg daily) was able to relieve discomfort related to dry eyes in patients with Sjögren's syndrome and induce favorable structural changes in the tear film.

RESUMO Objetivos: Avaliar o alívio de sintomas e sinais relacionados à secura ocular e na qualidade de vida de pacientes com síndrome de Sjögren tratados com o uso oral de pilocarpina na dose diária de 20mg. A frequência dos efeitos colaterais relatados com o tratamento também foi estudada. Métodos: Trata-se de estudo cruzado e placebo-controlado, que envolveu 32 pacientes com síndrome de Sjögren em uso de pilocarpina oral ou placebo, por dez semanas. Após duas semanas sem medicações, houve a inversão dos tratamentos para cada paciente, por mais dez semanas. As avaliações foram feitas por meio do questionário de qualidade de vida NEI-VFQ-25, questionário olho seco específico Ocular Surface Disease Index, tempo de ruptura do filme lacrimal não invasivo, tempo de ruptura do filme lacrimal com fluoresceína, avaliação da superfície ocular com os corantes fluoresceína e rosa Bengala, teste de Schirmer e teste de cristalização do filme lacrimal. Resultados: Houve melhora estatisticamente significante na qualidade de vida medida pelo questionário NEI-VFQ-25 e no desconforto ocular avaliado pelo Ocular Surface Disease Index, após o tratamento. Todos os testes clínicos sofreram influência favorável e estatisticamente significante durante a fase de tratamento com pilocarpina oral. Em relação à análise de amostras de lágrimas, ocorreram alterações estruturais indicando melhora no padrão de cristalização do filme lacrimal. Os efeitos colaterais com o uso de pilocarpina foram relatados por 96,8% dos pacientes com a pilocarpina e 56,2% com placebo. Sudorese foi o efeito colateral mais frequentemente relatado (pilocarpina = 67,74%; placebo = 11,11%). Conclusões: O uso oral de pilocarpina na dose diária de 20mg foi capaz de aliviar as queixas de desconforto relacionadas ao ressecamento ocular em pacientes com síndrome de Sjögren, produzir impacto positivo na qualidade de vida dos pacientes e induzir mudanças estruturais favoráveis no filme lacrimal, embora os efeitos colaterais relatados tenham ocorrido com alta frequência.

Tonic pupil after COVID-19 infection.

The latest global health threat is the ongoing outbreak of respiratory disease, which was named COVID-19 and multiple ever-evolving neurological complications have since been reported. We present the case of a patient with a bilateral tonic pupil in the postinfectious context of COVID 19. Brain magnetic resonance imaging and laboratory tests were normal, a 0.125% pilocarpine test confirmed the diagnosis.

Pupila tónica después de la infección por COVID-19 / Tonic pupil after COVID-19 infection

La última amenaza para la salud a nivel mundial es el continuo brote de la enfermedad respiratoria, que recibió el nombre de COVID-19, y desde entonces se han publicado múltiples complicaciones neurológicas que están en constante evolución. Presentamos el caso de un paciente con pupila tónica bilateral en el contexto postinfeccioso de COVID-19. La resonancia magnética cerebral y los estudios analíticos fueron normales, una prueba de pilocarpina al 0,125% confirmó el diagnóstico (AU)

The latest global health threat is the ongoing outbreak of respiratory disease, which was named COVID-19 and multiple ever-evolving neurological complications have since been reported. We present the case of a patient with a bilateral tonic pupil in the postinfectious context of COVID-19. Brain magnetic resonance imaging and laboratory tests were normal, a 0.125% pilocarpine test confirmed the diagnosis (AU)

Evaluation of the anticonvulsant and neuroprotective effect of intracerebral administration of growth hormone in rats.

INTRODUCTION: The growth hormone (GH) has been reported as a crucial neuronal survival factor in the hippocampus against insults of diverse nature. Status epilepticus (SE) is a prolonged seizure that produces extensive neuronal cell death. The goal of this study was to evaluate the effect of intracerebroventricular administration of GH on seizure severity and SE-induced hippocampal neurodegeneration. METHODOLOGY: Adult male rats were implanted with a guide cannula in the left ventricle and different amounts of GH (70, 120 or 220ng/3µl) were microinjected for 5 days; artificial cerebrospinal fluid was used as the vehicle. Seizures were induced by the lithium-pilocarpine model (3mEq/kg LiCl and 30mg/kg pilocarpine hydrochloride) one day after the last GH administration. Neuronal injury was assessed by Fluoro-Jade B (F-JB) staining. RESULTS: Rats injected with 120ng of GH did not had SE after 30mg/kg pilocarpine, they required a higher number of pilocarpine injections to develop SE than the rats pretreated with the vehicle, 70ng or 220ng GH. Prefrontal and parietal cortex EEG recordings confirmed that latency to generalized seizures and SE was also significantly higher in the 120ng group when compared with all the experimental groups. FJ-B positive cells were detected in the hippocampus after SE in all rats, and no significant differences in the number of F-JB cells in the CA1 area and the hilus was observed between experimental groups. CONCLUSION: Our results indicate that, although GH has an anticonvulsive effect in the lithium-pilocarpine model of SE, it does not exert hippocampal neuroprotection after SE.

The effects of pharmacological accommodation and cycloplegia on axial length and choroidal thickness / Efeitos da acomodação farmacológica e da cicloplegia no comprimento axial e na espessura da coroide

ABSTRACT Purpose: To investigate the effects of pharmacological accommodation and cycloplegia on ocular measurements. Methods: Thirty-three healthy subjects [mean (±SD) age, 32.97 (±5.21) years] volunteered to participate in the study. Measurement of the axial length, macular and choroidal thickness, refractive error, and corneal topography, as well as anterior segment imaging, were performed. After these procedures, pharmacological accommodation was induced by applying pilocarpine eye drops (pilocarpine hydrochloride 2%), and the measurements were repeated. The measurements were repeated again after full cycloplegia was induced using cyclopentolate eye drops (cyclopentolate hydrochloride 1%). The correlations between the measurements were evaluated. Results: A significant increase in subfoveal choroidal thickness after applying 2% pilocarpine was identified (without the drops, 319.36 ± 90.08 µm; with pilocarpine instillation, 341.60 ± 99.19 µm; with cyclopentolate instillation, 318.36 ± 103.0 µm; p<0.001). A significant increase in the axial length was also detected (without the drops, 23.26 ± 0.83 mm; with pilocarpine instillation, 23.29 ± 0.84 mm; with cyclopentolate instillation, 23.27 ± 0.84 mm; p=0.003). Comparing pharmacological accommodation and cycloplegia revealed a significant difference in central macular thickness (with pilocarpine instillation, 262.27 ± 19.34 µm; with cyclopentolate instillation, 265.93 ± 17.91 µm; p=0.016). Pilocarpine-related miosis (p<0.001) and myopic shift (p<0.001) were more severe in blue eyes vs. brown eyes. Conclusion: Pharmacological accommodation may change ocular measurements, such as choroidal thickness and axial length. This condition should be considered when performing ocular measurements, such as intraocular lens power calculations.(AU)

RESUMO Objetivo: Investigar os efeitos da acomodação farmacológica e da cicloplegia nas medições oculares. Métodos: participaram do estudo 33 voluntários saudáveis (média de idade [± DP], 32,97 anos [± 5,21 anos]). Foram medidos o comprimento axial, a espessura macular e coroidal e o erro refrativo, bem como realizados exames de imagem da topografia corneana e do segmento anterior. Em seguida, foi induzida a acomodação farmacológica aplicando-se colírio de pilocarpina (cloridrato de pilocarpina a 2%) e as medições foram repetidas nos participantes. As mesmas medições foram repetidas depois de induzir a cicloplegia completa com colírio de ciclopentolato (cloridrato de ciclopentolato a 1%) e foram avaliadas as correlações entre as medidas. Resultados: Identificou-se aumento significativo da espessura coroidal subfoveal com o uso da pilocarpina a 2% (sem colírio, 319,36 ± 90,08 µm; com a instilação de pilocarpina, 341,60 ± 99,19 µm; com a instilação de ciclopentolato, 318,36 ± 103,0 µm; p<0,001). Detectou-se também aumento significativo do comprimento axial (sem colírio, 23,26 ± 0,83 mm; com a instilação de pilocarpina, 23,29 ± 0,84 mm; com a instilação de ciclopentolato, 23,27 ± 0,84 mm; p=0,003). Ao se comparar a acomodação farmacológica e a cicloplegia, houve diferença significativa na espessura macular central (com a instilação de pilocarpina, 262,27 ± 19,34 µm; com a instilação de ciclopentolato, 265,93 ± 17,91 µm; p=0,016). Observou-se que a miose associada à pilocarpina (p<0,001) e o desvio miópico (p<0,001) foram mais severos nos olhos azuis que nos castanhos. Conclusão: A acomodação farmacológica pode alterar medidas oculares como a espessura da coroide e o comprimento axial. Essa possibilidade deve ser levada em consideração ao se efetuarem medições oculares, tais como cálculos de potência de lentes intraoculares.(AU)

Consistency between anticholinergic burden scales in patients with Sjögren's syndrome / Consistencia entre escalas de carga anticolinérgica en pacientes con síndrome de Sjögren

ABSTRACT Introduction: Sjögren's syndrome is the second most frequent autoimmune rheumatic disease and is characterized by exocrine gland involvement manifesting as sicca symptoms. The objective of this study was to estimate the degree of agreement between three anticholinergic burden scales related to the prescriptions of patients diagnosed with Sjögren's syndrome in Colombia. Materials and methods: An analytical concordance study was conducted. The weighted kappa coefficient with quadratic weights was used to identify consistency between the Anticholinergic Drug Scale (ADS), Anticholinergic Cognitive Burden Scale (ACB) and Anticholinergic Risk Scale (ARS), which address the prescriptions used for 3 months by patients with Sjögren s syndrome, in a population database. Results: A total of 15,696 patients with Sjögren's syndrome were identified, with a mean age of 65.4 ± 13.9 years, and 74.2% were women. A total of 94.1% of the patients received at least one topical lubricant, with carboxymethyl cellulose being the most commonly prescribed (22.9%), while oral pilocarpine was prescribed to 3.5% of patients. The ACB was the tool identified more antimuscarinic prescriptions (37.5%), followed by the ADS (35.3%) and ARS (25.2%). The greatest degree of agreement was found between the ADS and ACB (kappa 0.6520; confidence interval (CI): 0.6393-0.6648). Conclusions: Except for the ADS and ACB, little agreement was found between the three scales gauging the anticholinergic burden. Additional studies are needed to determine how these differences can impact the clinical outcomes of patients.

RESUMEN Introducción: El síndrome de Sjögren es la segunda enfermedad reumática autoinmune más frecuente, caracterizada especialmente por el compromiso de glándulas exocrinas manifestándose con síntomas sicca. El objetivo fue estimar el grado de acuerdo de 3 escalas de carga anticolinérgica en las prescripciones de pacientes con diagnóstico de síndrome de Sjögren en Colombia. Materiales y métodos: Estudio analítico de concordancia. Se empleó el coeficiente Kappa con ponderación cuadrática para identificar la consistencia entre los instrumentos Anticholin-ergic Drug Scale (ADS), Anticholinergic Cognitive Burden Scale (ACB) y Anticholinergic Risk Scale (ARS) de las prescripciones utilizadas durante 3 meses por pacientes con síndrome de Sjögren, a partir de una base de datos poblacional. Resultados: Se identificaron 15.696 pacientes con síndrome de Sjögren, con una edad media de 65,4 ±13,9 anos y el 74,2% de mujeres. El 94,1% recibieron por lo menos un lubricante tópico siendo el más prescrito la carboximetilcelulosa (22,9%), mientras que la pilocarpina oral se formuló en el 3,5% de ellos. La escala ACB fue la herramienta que más prescripciones anti-muscarínicas identificó (37,5%) seguida de la ADS (35,3%) y ARS (25,2%). El mayor grado de acuerdo se presentó entre las escalas ADS-ACB (Kappa: 0,6520; IC: 0,6393-0,6648). Conclusiones: Con excepción de las escalas ADS-ACB, hubo poco acuerdo al comparar las 3 escalas de carga anticolinérgica. Se requieren estudios adicionales para determinar cómo estas diferencias pueden impactar en la validez de los desenlaces clínicos de los pacientes.

Microbial safety implications of in-use topical diagnostic ophthalmic medications in eye clinics in Ghana.

PURPOSE: To determine the microbial contaminants and its clinical importance in topical diagnostic ophthalmic medications (cycloplegics/mydriatics and miotics) in eye clinics in Ghana. METHOD: A cross-section of eye clinics was sampled for the diagnostic agents (Atropine, Phenylephrine, Tropicamide and Cyclopentolate, Pilocarpine). Standard laboratory procedures and protocols were observed in culturing the samples on different Agars. Microscopy and various biochemical tests were performed to identify microbial species. Antimicrobial susceptibility testing was also performed to ascertain the clinical importance of the isolated microbes. RESULTS: A total of 113 samples were obtained, from which 334 bacteria were isolated which included Bacilli spp. 91(27.25%), Coagulase Negative Staphylococci spp. 59(17.66%), Moraxella spp. 47(14.07%), Staphylococcus aureus 41(12.27%), Streptococcus spp. 21(6.29%), Klebsiella spp. 20(5.99%), Pseudomonas spp. 13(3.89%), Proteus spp. 12(3.59%), Escherichia coli. 12 (3.59%), Serratia spp. 10(2.99%), Shigella spp. 7(2.09%), Salmonella spp. 1(0.3%). There were 96 isolated fungal contaminants mainly Penicillium spp. 41(42.71%), Cephalosporium spp. 19(19.79%), Cladosporium spp. 15(15.63%), Aspergillus spp. 13(13.54%), Cercospora spp. 8(8.33%). The diagnostic agent with the most bacteria contamination was Phenylephrine 90 (26.95%) and the least being Pilocarpine 49 (14.67%). Also, the diagnostic agent with the most fungal contamination was Cyclopentolate 29 (30.2%) and the least was Tropicamide and Pilocarpine with 15 (15.63%) each. Gentamicin and Ciprofloxacin were the only antibiotics that showed 100% activity against all the bacterial isolates. Fungal contaminants were more susceptible to Ketoconazole as compared to Fluconazole. CONCLUSION: Topical diagnostic ophthalmic preparations used in clinical settings in Ghana are contaminated with clinically important bacteria and fungi.

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.

Pupillometry in Chagas disease / Pupilometria na doença de Chagas

ABSTRACT Purpose: We investigated parasympathetic innervation abnormalities of the iris sphincter and ciliary muscles in chronic Chagas disease by measuring pupillary diameter and intraocular pressure. Methods: A group of 80 patients with Chagas disease was compared with 76 healthy individuals without chagasic infection. The following procedures were performed: pupillometry, hypersensitivity test to pilocarpine 0.125%, intraocular pressure measurement (IOP), basal pupil diameter (BPD), absolute pupillary constriction amplitude (ACA), relative pupillary constriction amplitude (RCA) and the presence of anisocoria. Results: The prevalence of anisocoria was higher in chagasic patients (p<0.01). These patients had mean basal pupillary diameter, mean photopic pupillary diameter and mean value of absolute pupillary constriction amplitude significantly lower than non-chagasic ones (p<0.01, mean difference -0.50mm), (p=0.02, mean difference -0.20mm), (p<0.01, mean difference -0.29mm), respectively. The relative pupillary constriction amplitude did not differ between the two groups (p=0.39, mean difference -1.15%). There was hypersensitivity to dilute pilocarpine in 8 (10%) of the chagasic patients in the right eye and in 2 (2.5%) in the left eye and in 1 (1.25%) in both eyes. The mean value of intraocular pressure had a marginal statistical significance between the two groups (p=0.06, mean difference -0.91mmHg). Conclusions: Patients with chagasic infection may exhibit ocular parasympathetic dysfunction, demonstrable by pupillometry and the dilute pilocarpine hypersensitivity test.

RESUMO Introdução: Investigaram-se anormalidades da inervação parassimpática dos músculos esfíncter da íris e ciliar na doença de Chagas crônica, através de medidas pupilares e da pressão intraocular. Métodos: Foram estudados dois grupos, um com 80 chagásicos e outro com 76 indivíduos saudáveis sem infecção chagásica. Foram realizados os seguintes procedimentos: pupilometria, teste de hipersensibilidade à pilocarpina a 0,125%, medida da pressão intraocular (PIO), diâmetro basal da pupila (DBP), amplitude de constrição pupilar absoluta (ACA), amplitude de constrição pupilar relativa (ACR), e presença de anisocoria. Resultados: A prevalência de anisocoria foi maior nos chagásicos (p<0,01). Estes pacientes apresentaram diâmetro basal pupilar médio, diâmetro fotópico médio e valor médio da amplitude de constrição pupilar absoluta, significativamente menores que os não chagásicos, (p<0,01, diferença de média -0,50mm), (p=0.02, diferença de média -0,20mm), (p<0,01, diferença de média -0,29mm), respectivamente. A amplitude de constrição pupilar relativa não diferiu entre os dois grupos (p=0,39, diferença de média -1,15%). Houve hipersensibilidade à pilocarpina diluída em 8 (10%) chagásicos no olho direito em 2 (2,5%) no olho esquerdo e em 1 (1,25%) em ambos os olhos. O valor médio da pressão intraocular teve significância marginal entre os dois grupos (p=0,06, diferença de média -0,91mmHg). Conclusões: Pacientes com infecção chagásica podem apresentar disfunção parassimpática ocular, demonstrável pela pupilometria e pelo teste de hipersensibilidade à pilocarpina diluída.

Terapia farmacológica y avances terapéuticos en xerostomía e hiposalivación / Pharmacological therapy and therapeutic advancesin xerostomy and hyposalivation

La saliva juega un rol determinante en el mantenimiento y función de los tejidos orales, donde un decremento en los niveles del flujo salival conllevan a una hiposalivación o hiposialia, trayendo consigo una serie de características que propician un ambiente ideal para la instalaciónde microorganismos oportunistas y condiciones nocivas para la saludoral y sistémica de los pacientes. Hoy en día existen múltiples causas que conllevan a una hiposialia, entre ellas el síndrome de Sjõgren, la radioterapia de haz externo, entre otras, los cuales se han puesto a prueba mediante sialogogos farmacológicos como pilocarpina, cevimelina, betanecoly carbacolina, además de alternativas terapéuticas para revertir los signos obtenidos por la hiposalivación y mitigar los síntomas de xerostomía. El objetivo del presente es realizar una revisión de literatura sobre el tratamiento farmacológico en hiposalivación y xerostomía ensíndrome de Sjõgren y radioterapia de haz externo.

Saliva plays a determinant role in the maintenance and function of oral tissues, where a decrease in salivary flow levels leads to hyposalivation or hyposialia, bringing with it a series of characteristics that provide anideal environment for the installation of opportunistic microorganisms and conditions harmful to the oral and systemic health of patients.Today there are many causes that lead to hyposialia, including Sjögren’ssyndrome, external beam radiotherapy, among others, which have beentested by pharmacological sialogogs such as pilocarpine, cevimelin, betanecol and carbacoline, in addition to therapeutic alternativesto reverse the signs obtained by hyposalivation and to mitigate the symptoms of xerostomia. The objective of the present is to make a reviewof the literature on the pharmacological treatment in hyposalivation and xerostomia in Sjögren’s syndrome and external beam radiotherapy.

Impaired executive functions in experimental model of temporal lobe epilepsy / Prejuízo das funções executivas no modelo experimental de epilepsia do lobo temporal

ABSTRACT Objective The present study aimed to investigate cognitive and behavioural changes consistent with attention deficit hyperactivity disorder (ADHD -like behavior in male Wistar rats with temporal lobe epilepsy (TLE). Method Male Wistar rats at 25 day of age were submitted to animal model of TLE by pilocarpine injection (350 mg/kg, ip) and a control group received saline 0.9%. The animals were continuously video monitored up to the end of experiments. The behavioural tests (open field, elevated plus maze and operant conditioning box) started from 60 days postnatal. Results Animals with TLE exhibited elevated locomotor activity, reduced level of anxiety-related behavior, impulsivity and impaired visuospatial working memory. Conclusion Taken as a whole, we concluded that animals with TLE exhibited some cognitive and behavioural changes consistent with ADHD-like behavior.

RESUMO Objetivo O presente estudo teve como objetivo investigar as alterações cognitivas e comportamentais consistentes com o comportament de transtorno de deficit de atenção e hiperatividade (TDAH) -like em ratos Wistar machos com epilepsia do lobo temporal (ELT). Método Ratos Wistar machos com 25 dias de vida foram submetidos a modelo animal de ELT pela injeção de pilocarpina (350 mg / kg, ip) e grupo controle recebeu salina 0,9%. Os animais foram monitorados continuamente por vídeo até ao final dos experimentos. Os testes comportamentais (campo aberto, labirinto em cruz elevado e caixa de condicionamento operante) começaram a partir de 60 dias pós-natal. Resultados Os animais com ELT exibiram aumento da atividade locomotora, redução do comportamento relacionado com a ansiedade, impulsividade e prejuízo da memória de trabalho visuospatial. Conclusão Em conjunto, concluímos que os animais com ELT apresentaram algumas alterações cognitivas e comportamentais consistentes com o comportamento TDAH-like.

In vitro effects of Pilocarpus microphyllus extracts and pilocarpine hydrochloride on Rhipicephalus (Boophilus) microplus / Efeitos in vitro do extrato de Pilocarpus microphyllus e do cloridrato de pilocarpina sobre Rhipicephalus (Boophilus) microplus

Abstract The aim of this study was to assess the activity of aqueous (AE) and ethanolic extracts (EE) and pilocarpine hydrochloride, which were extracted and isolated from Pilocarpus microphyllus (Jaborandi), respectively, on Rhipicephalus (Boophilus) microplus. High performance liquid chromatography (HPLC) was performed to quantify these compounds. Larval packet and adult immersion tests were conducted with different concentrations. Five AE and EE concentrations, ranging from 6.2 to 100.0 mg mL–1, and six concentrations of pilocarpine hydrochloride, ranging from 0.7 to 24.0 mg mL–1, were tested. The lethal concentration (LC50) of each extract for larvae and engorged females was calculated through Probit analysis. The concentration of pilocarpine hydrochloride obtained from the EE and the AE was 1.3 and 0.3% (m/m), respectively. Pilocarpine hydrochloride presented the highest acaricidal activity on larvae (LC50 2.6 mg mL–1) and engorged females (LC50 11.8 mg mL–1) of R.(B.) microplus, followed by the EE which presented LC50 of 56.4 and 15.9 mg mL–1, for larvae and engorged females, respectively. Such results indicate that pilocarpine hydrochloride has acaricidal activity, and may be the primary compound responsible for this activity by P. microphyllus EE.

Resumo O objetivo desse estudo foi avaliar a atividade dos extratos aquoso (AE) e etanólico (EE) e do cloridrato de pilocarpina, que foram, respectivamente, extraídos e isolado de Pilocarpus microphyllus (Jaborandi), sobre Rhipicephalus (Boophilus) microplus. Cromatografia líquida de alta eficiência foi realizada para quantificação dos compostos. Testes de pacote de larvas e de imersão de adultos foram realizados com diferentes concentrações. Cinco concentrações do AE e EE variando de 6,2 a 100,0 mg mL–1 e seis concentrações do cloridrato de pilocarpina variando de 0,7 a 24,0 mg mL–1 foram testadas. A concentração letal (CL50) de cada extrato para larvas e fêmeas ingurgitadas foi estimada por meio da análise Probit. A concentração de cloridrato de pilocarpina obtida do EE e AE foi de 1,3 e 0,3% (m/m), respectivamente. O cloridrato de pilocarpina apresentou a maior atividade carrapaticida sobre larvas (CL50 2,6 mg mL–1) e fêmeas ingurgitadas (CL50 11,8 mg mL–1) de R. (B.) microplus, seguido do EE que apresentou CL50 de 56,4 e 15,9 mg mL–1, para larvas e fêmeas ingurgitadas, respectivamente. Tais resultados indicam que o cloridrato de pilocarpina apresenta atividade carrapaticida e pode ser o principal responsável pela atividade acaricida do EE de P. microphyllus.

Condutividade e teste quantitativo coulométrico na triagem neonatal para fibrose cística / Sweat conductivity and coulometric quantitative test in neonatal cystic fibrosis screening

Resumo Objetivo Comparar os resultados obtidos no teste do suor pelo método da condutividade e a dosagem coulométrica de cloreto no suor em recém0nascidos (RN) suspeitos da triagem neonatal para fibrose cística (FC). Métodos O teste do suor foi feito simultaneamente pelos dois métodos em crianças com e sem FC. Os valores de corte para confirmar FC foram na condutividade > 50 mmol/L e no teste coulométrico > 60 mmol/L. Resultados Fizeram o teste do suor por condutividade e dosagem coulométrica simultaneamente 444 RN sem FC (185 do sexo masculino, 234 do feminino e 24 não informado) e obtiveram resultado mediano de 32 mmol/L e 12 mmol/L respectivamente. Para os noventa RN com FC os valores medianos de condutividade e dosagem coulométrica foram 108 mmol/L e 97 mmol/L respectivamente. O índice de falso positivo para condutividade foi de 16,7% e em todos os pacientes FC foi superior a 50 mmol/L, o que confere ao método 100% de sensibilidade (IC 95% = 93,8 a 97,8), especificidade de 96,2% (IC 95% = 93,8 a 97,8), valor preditivo positivo 83,3 (IC 95% = 74,4 a 91,1), valor preditivo negativo 100% (IC 95% = 90,5 a 109,4) e acurácia 9,8%. A correlação entre os métodos foi de r = 0,97 (p > 0,001).O melhor valor de corte sugerido foi de 69,0 mmol/L, coeficiente de kappa = 0,89. Conclusão O teste da condutividade apresentou excelente correlação com o quantitativo coulométrico, alta sensibilidade e especificidade e pode ser usado no diagnóstico da FC em crianças detectadas pela triagem neonatal.

Abstract Objective To compare the results obtained with the sweat test using the conductivity method and coulometric measurement of sweat chloride in newborns (NBs) with suspected cystic fibrosis (CF) in the neonatal screening program. Methods The sweat test was performed simultaneously by both methods in children with and without CF. The cutoff values to confirm CF were >50 mmol/L in the conductivity and >60 mmol/L in the coulometric test. Results There were 444 infants without CF (185 males, 234 females, and 24 unreported) submitted to the sweat test through conductivity and coulometric measurement simultaneously, obtaining median results of 32 mmol/L and 12 mmol/L, respectively. For 90 infants with CF, the median values of conductivity and coulometric measurement were 108 mmol/L and 97 mmol/L, respectively. The false positive rate for conductivity was 16.7%, and was higher than 50 mmol/L in all patients with CF, which gives this method a sensitivity of 100% (95% CI: 93.8-97.8), specificity of 96.2% (95% CI: 93.8-97.8), positive predictive value of 83.3% (95% CI: 74.4-91.1), negative predictive value of 100% (95% CI: 90.5-109.4), and 9.8% accuracy. The correlation between the methods was r = 0.97 (p > 0.001). The best suggested cutoff value was 69.0 mmol/L, with a kappa coefficient = 0.89. Conclusion The conductivity test showed excellent correlation with the quantitative coulometric test, high sensitivity and specificity, and can be used in the diagnosis of CF in children detected through newborn screening.

Sweat conductivity and coulometric quantitative test in neonatal cystic fibrosis screening.

OBJECTIVE: To compare the results obtained with the sweat test using the conductivity method and coulometric measurement of sweat chloride in newborns (NBs) with suspected cystic fibrosis (CF) in the neonatal screening program. METHODS: The sweat test was performed simultaneously by both methods in children with and without CF. The cutoff values to confirm CF were >50 mmol/L in the conductivity and >60 mmol/L in the coulometric test. RESULTS: There were 444 infants without CF (185 males, 234 females, and 24 unreported) submitted to the sweat test through conductivity and coulometric measurement simultaneously, obtaining median results of 32 mmol/L and 12 mmol/L, respectively. For 90 infants with CF, the median values of conductivity and coulometric measurement were 108 mmol/L and 97 mmol/L, respectively. The false positive rate for conductivity was 16.7%, and was higher than 50 mmol/L in all patients with CF, which gives this method a sensitivity of 100% (95% CI: 93.8-97.8), specificity of 96.2% (95% CI: 93.8-97.8), positive predictive value of 83.3% (95% CI: 74.4-91.1), negative predictive value of 100% (95% CI: 90.5-109.4), and 9.8% accuracy. The correlation between the methods was r=0.97 (p>0.001). The best suggested cutoff value was 69.0 mmol/L, with a kappa coefficient=0.89. CONCLUSION: The conductivity test showed excellent correlation with the quantitative coulometric test, high sensitivity and specificity, and can be used in the diagnosis of CF in children detected through newborn screening.