O uso do cloridrato de piridoxina para induzir estro em cadelas / The use of pyridoxine chloridrate to induce estrus in female dogs

Os agonistas dopaminérgicos são utilizados para induzir estro em cadelas, pois atuam na síntese e liberação de prolactina. Objetivou-se avaliar o efeito da piridoxina como indutor de estro em cadelas por agir na neurotransmissão dopaminérgica. Foram selecionadas 40 cadelas em anestro, divididas em quatro grupos experimentais, tratadas com 10mg/kg/dia (G1) e 50mg/kg/dia (G2) de cloridrato de piridoxina, 5µg/kg/dia (G3) de cabergolina e grupo controle/placebo (G4) por até 20 dias. Foram realizadas citologias vaginais a cada 24h para acompanhamento do ciclo estral e análises hormonais (FSH, LH e PRL) no dia zero e 120h do início do tratamento. As cadelas do G3 (100%) manifestaram proestro após 12 dias de tratamento aproximadamente, tempo inferior aos demais grupos (P<0,05). Apenas uma cadela do G1 e uma do G2 ficaram gestantes contra oito fêmeas do G3 e nenhuma do G4 (P<0,05). As concentrações plasmáticas de prolactina foram reduzidas nas fêmeas do G2 e G3 (P<0,05). As demais avaliações hormonais não sofreram influência do tratamento (P>0,05). O cloridrato de piridoxina foi ineficiente para induzir estro em cadelas, mas foi capaz de suprimir a prolactina, de forma semelhante à cabergolina, quando utilizado na dose de 50mg/kg/dia.(AU)

Dopaminergic agonists are used to induce estrus in female dogs as they act in the synthesis and release of prolactin. The objective of this study was to evaluate the effect of pyridoxine as an inducer of estrus by acting on dopaminergic neurotransmission. A total of 40 female dogs in anestrous were divided into four experimental groups treated with 10mg/kg/day (G1) and 50mg/kg/day (G2) of pyridoxine hydrochloride, 5µg/kg/day (G3) of cabergoline and control group/placebo (G4) for up to 20 days. Vaginal cytologies were performed every 24h for follow-up of the estrous cycle and hormonal analyzes (FSH, LH and PRL) on day zero and 120 hours after the start of treatment. The female dogs from G3 (100%) showed proestrus after 12 days of treatment, less time than the other groups (P< 0.05). Only one female from G1 and one from G2 were pregnant against eight from G3 and none from G4 (P< 0.05). Plasma concentrations of prolactin were reduced by treatment in females from G2 and G3 (P< 0.05). The other hormonal evaluations were not influenced by the treatment (P> 0.05). Pyridoxine chloridrate was inefficient to induce estrus in female dogs but was able to suppress prolactin when used at a dose of 50mg/kg/day.(AU)

Resolution of headache after reduction of prolactin levels in hyperprolactinemic patients / Resolução de cefaleia após redução dos níveis de prolactina em pacientes com hiperprolactinemia

Abstract Prolactin (PRL) secreting adenomas are associated with high incidence of headache. The role of hyperprolactinemia in the headache context is not clear, nor is the effect of its treatment on headache. Methods: The present longitudinal study evaluated hyperprolactinemic patients (69), in terms of presence and characteristics of headache before and after hyperprolactinemia treatment. Results: Headache was reported by 45 (65.2%) patients, independent of the etiology of hyperprolactinemia. The migraine phenotype was the most prevalent (66.6%). Medications used in the treatment of headache not changed during the study. The first line of treatment of hyperprolactinemia was dopaminergic agonists. In the last reevaluation, PRL level under treatment was within the reference range in 54.7% of the cases, and it was observed complete or partial resolution of the headache in 75% of the cases. The median PRL at this time in patients with complete headache resolution was 17 ng/mL, in those who reported partial recovery was 21 ng/mL, and in those in whom the headache did not change was 66 ng/mL, with a significant difference between the group with complete headache resolution vs. the group with unchanged headache (p=0.022). In the cases with complete headache resolution, the median fall on PRL levels was 89% and in those cases with partial headache resolution 86%, both significantly different (p<0.001) from the fall in the cases with an unchanged headache. Conclusion: Data allow us to conclude that, in this series, in the majority of cases the reduction in the level of PRL was followe3d by cessation or relief of the pain.

Resumo Os adenomas secretores de prolactina (PRL) estão associados à alta incidência de cefaleia. O papel da hiperprolactinemia no contexto da dor de cabeça não está claro, nem o efeito da redução dos níveis da PRL na cefaleia. Métodos: O presente estudo longitudinal avaliou pacientes hiperprolactinêmicos (69), quanto à presença e às características da cefaleia antes e após o tratamento da hiperprolactinemia. Resultados: Cefaleia foi relatada por 45 (65,2%) pacientes, independente da etiologia da hiperprolactinemia. O fenótipo de enxaqueca foi mais prevalente (66,6%). Os medicamentos usados ​​no tratamento da cefaleia não foram alterados durante o estudo. A primeira linha de tratamento da hiperprolactinemia foram os agonistas dopaminérgicos. Na última reavaliação, o nível de PRL sob tratamento estava dentro da faixa de referência em 54,7% dos casos, observando-se resolução completa ou parcial da cefaleia em 75% dos casos. A mediana de PRL neste momento em pacientes com resolução completa da cefaleia foi de 17 ng/mL, nos que relataram recuperação parcial foi de 21 ng/mL, e naqueles em que a cefaleia não se alterou foi de 66 ng/mL, com uma diferença significativa entre o grupo com resolução completa da cefaleia versus o grupo com cefaleia inalterada (p=0,022). Nos casos com resolução completa da cefaleia, a queda mediana nos níveis de PRL foi de 89% e nos casos com resolução parcial de cefaleia de 86%, ambos significativamente diferentes (p<0,001) da queda nos casos com cefaleia inalterada. Conclusão: Os dados permitem concluir que, nesta série, na maioria dos casos, a redução do nível de PRL foi seguida pela cessação ou alívio da dor.

Pharmacological treatment with cabergoline in three cats with acromegaly / Tratamiento farmacológico con cabergolina en tres gatos con acromegalia / Tratamento farmacológico com cabergolina em três gatos com acromegalia

Abstract Anamnesis: Three cats diagnosed with diabetes mellitus (DM) were referred for examination due to the presence of insulin resistance signs, which included polyuria, polydipsia, polyphagia and high fructosamine levels, even with insulin glargine doses greater than 2 U/Kg/application. Clinical and laboratory findings: All patients had enlarged facial features along with increased interdental space. The biochemical tests revealed high IGF-1 concentrations. The magnetic resonance imaging displayed enlarged pituitary gland in one of the cats and images compatible with a pituitary macroadenoma in the other two. Acromegaly was the final diagnosis. Treatment approach: Oral cabergoline at 10 µg/Kg every 48 h was administered. Conclusion: The treatment with cabergoline successfully decreased IGF-1 concentrations and all insulin resistance signs, and it enhanced glycemic control for the DM in the three cats. Our results suggest cabergoline could be used for the treatment of acromegaly in cats.

Resumen Anamnesis: Tres gatos diagnósticados con diabetes mellitus (DM) fueron referidos para ser examinados debido a la presencia de signos de resistencia a la insulina, que incluían poliuria, polidipsia, polifagia, y de valores elevados de fructosamina, incluso con dosis de insulina glargina mayor a 2 U/Kg/aplicación. Hallazgos clínicos y de laboratorio: Los tres gatos presentaron amplios rasgos faciales con aumento de los espacios interdentales. En la bioquímica sanguínea, la concentración de IGF-1 fue hallada elevada. La imagen por resonancia magnética mostró agrandamiento de la glándula hipófisis en uno de los gatos, e imágenes compatibles con un macroadenoma de hipófisis en los otros dos. El diagnóstico final fue de acromegalia. Abordaje terapéutico: Se administraron 10 µg/Kg de cabergolina cada 48 h, via oral. Conclusión: El tratamiento con cabergolina logró disminuir las concentraciones de IGF-1 y todos los signos de resistencia a la insulina con mejor control glucémico de la DM en los tres gatos. Los anteriores hallazgos sugieren que la cabergolina es una opción viable para el tratamiento de la acromegalia en gatos.

Resumo Anamnese: Três gatos diagnosticados com diabetes mellitus (DM) foram encaminhados para exame devido à presença de sinais de resistência à insulina, que incluíram poliúria, polidipsia, polifagia e altos níveis de fructosamina, mesmo com doses de insulina glargina superiores a 2 U/Kg/aplicação. Achados clínicos e de laboratório: Os três gatos apresentavam mudanças dos rasgos faciais e aumento do espaço interdental. As provas bioquímicas revelaram altas concentrações de IGF-1. A ressonância magnética mostrou incremento do tamanho da glândula pituitária em um dos gatos e imagens compatíveis com um macroadenoma pituitário nos outros dois. Com estes dados chegou-se ao diagnóstico de acromegalia. Enfoque terapêutico: Foram dadas 10 µg/Kg de cabergolina a cada 48 h, via oral. Conclusão: O tratamento com cabergolina diminuiu com sucesso as concentrações de IGF-1 e todos os sinais de resistência à insulina e aumentou o controlo glicémico para a DM nos três gatos. Conclusões anteriores evidenciam que a cabergolina é uma opção viável para o tratamento da acromegalia em gatos.

Novedoso profármaco derivado de la lilolidina con actividad dopaminérgica central / Novel prodrug derivative from lilolidine with central dopaminergic activity

La desregulación de la neurotransmisión dopaminérgica central ha sido relacionada con enfermedades neurodegenerativas, tales como la enfermedad de Parkinson y la Corea de Huntington. En las últimas décadas son muchos los compuestos con actividad dopaminérgica central que se han diseñado, sintetizado y evaluado farmacológicamente y, a pesar de estos esfuerzos, no se ha logrado obtener un fármaco efectivo capaz de mejorar o curar estas patologías. Con el fin de contribuir en esta búsqueda primordial, en el presente trabajo se describe el diseño, la síntesis y la evaluación farmacológica del derivado de la lilolidina, clorhidrato de 6-(2-aminoindanil)-N-(2,4,5,6-tetrahidro-1H-pirrolo[3,2,1-ij]quinolina) 4 (MAIL), con el propósito de restablecer la homeostasis de la transmisión dopaminérgica en la enfermedad de Parkinson y/o la Corea de Huntington. Para ello, se utilizaron las diferentes estrategias nigroesclásicas y heterocíclicas enmarcadas en la síntesis orgánica a través de una ruta convergente. Asimismo, se realizó la evaluación farmacológica preliminar, al determinar el comportamiento estereotipado en ratas Sprague-Dawley cuando les fue administrado el derivado de la lilolidina, por las vías ICV (intracerebroventricular) e IE (intraestriatal). Los resultados obtenidos del compuesto 4 mostraron una acción central como agonista, a través de mecanismos dopaminérgicos.

Central dopaminergic neurotransmission deregulation has been related with neurodegenerative sicknesses, like Parkinson’s disease and Huntington’s Chorea. During the last decades, many compounds with dopaminergic activity have been designed, synthesized and pharmacologically evaluated, but despite all these efforts, an effective drug able to improve or cure these pathologies has not been achieved. With the purpose to contribute in this essential search, this work describes the design, synthesis and pharmacological evaluation of the lilolidine derivative, 6-(2-aminoindanyl)-N-(2,4,5,6-tetrahydro-1H-pyrrolo[3,2,1-ij]quinoline hydrochloride) 4 (MAIL), with the purpose of restoring the homeostasis of dopaminergic transmission in Parkinson’s disease and/or Huntington’s Chorea. To perform that, different organic synthesis classic and heterocyclic strategies were employed through a convergent route. Also, a preliminar pharmacological evaluation was done, where the stereotyped behavior of Sprague-Dawley rats was studied after the ICV (intracerebroventricular) and IE (intrastriatum) administration of the lilodine derivative. The results obtained of compound 4 showed a central dopaminergic agonist activity through dopaminergic mechanisms.

Suppressive Effects of Kambaku-taiso-to on the Yawning Induced by Dopaminergic Agonist in Rats / 日本東洋医学雑誌

The present experiments were performed to investigate the potential role of Kambaku taiso-to (Gan mai da zao tang) in modifying the occurrence of yawning in rats. Subcutaneous injection of talipexole, a selective dopamine D-2 receptor agonist, at 5-100μg/kg, elicits yawning behavior for over one hour, the maximal effect being observed at a dose of 25μg/kg. Kambaku-taiso-to significantly suppressed the incidence of yawning induced by talipexole. These results suggest that Kambaku-taiso-to exerts a suppressive effect on the incidence of yawning.

The safety and the therapeutic efficacy of ?-dihydroergocriptin in the treatment of Parkinson's disease by multi-center clinical trial / 中华老年医学杂志

Objective To study the therapeutic efficacy of dopaminergic agonists,? dihydroergocriptin(Cripar) by multiple center opened trial Methods Sixty cases of Parkinson's disease were divided into two groups: monotherapy group(27 cases) and combined therapy group(33 cases) The improvement in both groups after therapy was observed Results Patients undergone monotherapy were treated with ? dihydroergocriptin and those undergone combined therapy were treated with combined use of ? dihydroergocriptin and L doparmine All patients after treatment showed improvement of clinical symptoms There were 7 patients (28 0%) in the monotherapy group and 13 patients (39 4%) in the combined therapy group markedly improved Evaluation of therapeutic improvement by modified UPDRS revealed that the average scores was 5 01 in monotherapy group and was 6 39( P