Lactation Induction in a Commissioned Mother by Surrogacy: Effects on Prolactin Levels, Milk Secretion and Mother Satisfaction / Indução da lactação em mãe por útero de substituição: efeitos na concentração de prolactina, produção láctea e satisfação materna

Abstract Case report of a 39-year-old intended mother of a surrogate pregnancy who underwent induction of lactation by sequential exposure to galactagogue drugs (metoclopramide and domperidone), nipple mechanical stimulation with an electric pump, and suction by the newborn. The study aimed to analyze the effect of each step of the protocol on serum prolactin levels, milk secretion and mother satisfaction, in the set of surrogacy. Serum prolactin levels and milk production had no significant changes. Nevertheless, themother was able to breastfeed for four weeks, and expressed great satisfaction with the experience. As a conclusion, within the context of a surrogate pregnancy, breastfeeding seems to bring emotional benefits not necessarily related to an increase in milk production.

Resumo Relato de caso de mãe por útero de substituição, de 39 anos de idade, submetida a indução da lactação por exposição sequencial a drogas galactogogas (metoclopramida e domperidona), estimulação mamilar mecânica com bomba elétrica, e sucção pelo recém-nascido. O estudo teve como objetivo analisar os efeitos de cada etapa do protocolo na concentração sérica de prolactina, no volume de secreção láctea e na satisfação materna. A concentração sérica de prolactina e a produção láctea não apresentaram mudanças significativas. Entretanto, a mãe foi capaz de amamentar a criança por quatro semanas, e manifestou grande satisfação com a experiência. Como conclusão, no contexto de maternidade por útero de substituição, o aleitamento materno parece promover benefícios emocionais, não necessariamente relacionados ao aumento do volume de leite.

Fresh, equilibrated and post-thaw sperm quality of Brycon orbignyanus (Valenciennes, 1850) and Prochilodus lineatus (Valenciennes, 1837) treated with either salmon GnRHa and domperidone or pituitary extract

The effects of reduced doses of Ovaprim™ (GnRHa + domperidone) on sperm release of Brycon orbignyanus and Prochilodus lineatus were evaluated. Furthermore, sperm quality was compared among fresh, equilibrated and post-thaw samples. Males received a single and reduced dose of Ovaprim™ (0.125 or 0.25 ml/kg); control males received pituitary extract (cPE; 3 mg/kg). Fresh sperm was evaluated for volume, concentration, seminal plasma osmolality and seminal plasma pH. Then sperm was diluted in a freezing medium, equilibrated for 15-20 min and frozen in nitrogen vapor vessel (dry-shipper). Sperm motility was analyzed during 60 s post-activation in fresh, equilibrated and post-thaw samples. Sperm quality of males treated with Ovaprim™ (both doses) were not different from that of cPE-treated males, thus these data were pooled. In B. orbignyanus, motility was higher in fresh (99%) than in equilibrated sperm (81%); post-thaw motility dropped to 42%. In P. lineatus, motility was similar in fresh (99%) and equilibrated sperm (92%); post-thaw motility was 73%. Motility decreased as a function of time post-activation, and this decrease was significant after 60 s in fresh and equilibrated sperm, and as soon as 30 s in post-thaw sperm, in both species. Ovaprim™ at 1/4 of the recommended dose can successfully replace cPE.

O efeito de doses reduzidas de Ovaprim® (GnRHa + domperidona) na liberação do sêmen de Brycon orbignyanus e Prochilodus lineatus foi avaliado. Além disso, a qualidade do sêmen foi comparada entre as amostras frescas, equilibradas e descongeladas. Os machos receberam dose única e reduzida de Ovaprim® (0,125 ou 0,25 ml/kg); os machos-controle receberam extrato de hipófise (cPE; 3 mg/kg). O sêmen fresco foi avaliado quanto ao volume, concentração, e osmolalidade e pH do plasma seminal. Em seguida, o sêmen foi diluído num meio de congelamento, equilibrado por 15-20 min e congelado em botijão de vapor de nitrogênio (dry-shipper). A motilidade espermática foi analisada durante 60 s pós-ativação no sêmen fresco, equilibrado e descongelado. A qualidade do sêmen não diferiu entre os machos tratados com Ovaprim® (ambas as doses) ou cPE, assim foi feito um pool desses dados. Em B. orbignyanus, a motilidade foi maior no sêmen fresco (99%) do que no equilibrado (81%); a motilidade do sêmen descongelado caiu para 42%. Em P. lineatus, a motilidade foi semelhante entre o sêmen fresco (99%) e equilibrado (92%); a motilidade do sêmen descongelado foi 73%. A motilidade caiu em função do tempo pós-ativação, e essa queda foi significante após 60 s no sêmen fresco e equilibrado, e tão precoce quanto 30 s no sêmen descongelado, em ambas as espécies. Ovaprim® a 1/4 da dose recomendada pode substituir o cPE com sucesso.

Trastornos funcionales gastrointestinales: metoclopramida, domperidona y trimebutina / Functional gastrointestinal disorders: metoclopramide, domperidone and trimebutine

Muchos de los síntomas digestivos en niños, no están asociados a cambios patológicos, osea, en los trastornos funcionales no hay alteración en la mucosa, como tampoco en la endoscopia. Estas alteraciones son muy amplias, no solamente incluye el reflujo gastroesofágico. Los procinéticos aumentan la actividad colinérgica. La metoclopramida, es un antagonista dopaminérgico que aumenta el tono del esfínter esofágico inferior y mejora el vaciamiento gástrico. La domperidona, es un antagonista periférico de la dopamina con propiedades procinéticas y antieméticas. La trimetutina, es un regulador de la motilidad del tracto digestivo inferior.

Many of the gastrointestinal symptoms in children are not associated with pathological changes, that is, in functional disorders there is no alteration in the mucosa, nor in endoscopy. These changes are extensive, not only includes gastroesophageal reflux. Prokinetics increase cholinergic activity. Metoclopramide is a dopaminergic antagonist that increases lower esophageal sphincter tone and enhances gastric emptying. Domperidone is a peripheral dopamine antagonist with prokinetic and antiemetic properties. Trimetubine, is a regulator of the lower digestive tract motility.

Uso de galactagogos na prática clínica para o manejo do aleitamento materno / Use of galactagogues in the practical clinical for the management of breastfeeding

Galactagogos são substâncias que auxiliam o início e a manutenção da produção adequada de leite, porém, alguns autores têm adotado o termo galactagogo. Nesta revisão foram selecionados artigos nos bancos de dados eletrônicos PubMEd, Medline, Lilacs e SciELO nos últimos 10 anos, nas línguas portuguesa e inglesa, utilizando os descritores aleitamento materno, lactação, transtornos da lactação, uso de medicamentos. Os fármacos galactagogos utilizados atualmente são antagonistas dopaminérgicos, que aumentam a prolactina sérica. Os mais conhecidos são metoclopramida e domperidona. O mecanismo de ação de alguns medicamentos e de plantas com relato de efeito galactagogo ainda são desconhecidos. Antes de indicar galactagogos é necessário avaliar freqüência e técnica da amamentação; uma vez que, a baixa produção do leite pode estar associada com técnica inadequada da amamentação, esvaziamento incompleto das mamas e baixa freqüência das mamadas. Por conseguinte, grande parte dos problemas em aleitamento materno pode ser prevenido e solucionado com conhecidas práticas que mantenham a lactação fisiológica, como amamentação sob livre demanda, pega adequada do complexo aréolo-mamilar e esvaziamento das mamas.

Galactagogues are substances that help the beginning and the maintenance of the adequate output of milk, by, some authors has adopted the term galactogogue. In this revision were selected articles in the electronic databases PubMEd, Medline, Lilacs and SciELO in the last 10 years, in the English and Portuguese languages, utilizing the descritores breastfeeding, lactation, perturbations of the lactation, use of medicines. The medicines galactagogues utilized at present are dopamine antagonists which increase the level of prolactin. The most know medicines are metoclopramide and domperidone. The mechanisms of action of some medicines and of plants with accounts of effect galactagogue are still unknown. Despite of easier and comfortable, the prescription of galactagogues should not be used for replace the correct management of problems related to the breastfeeding. Like this most of the problems in maternal breast-feeding can be prevented and solved with practical acquaintances that maintain the physiological lactation, as breastfeeding under free demand, adequate suckling and emptying of the breast.

Role of ion channel modifiers in reversal of morphine-induced gastrointestinal inertia by prokinetic agents in mice.

Prokinetic drugs like mosapride, domperidone etc, are used to treat gastrointestinal delay. Though the receptor-mediated actions of these agents have been studied, involvement of ion channels in reversing morphine-induced gastrointestinal inertia by prokinetic agents has not been explored. Charcoal meal test was used to measure small intestinal transit (SIT) in adult male Swiss albino mice. Animals were given ion channel modifiers and prokinetic drugs intragastrically. Reversal of morphine-induced gastrointestinal delay by mosapride was decreased significantly by CaCl2, minoxidil and glibenclamide. Similarly, domperidone's effect on morphine was decreased by CaCl2, nifedipine, minoxidil and glibenclamide significantly. The results reveal that ion channel modifiers counteract the prokinetic effects of mosapride or domperidone.

Effect of Ovaprim doses and latency periods on induced spawning of Clarias batrachus: observation on larval deformity.

Induced spawning of C. batrachus was conducted at different Ovaprim dose and latency period combinations to observe the deformed larvae among the hatchlings. For the purpose, four doses of Ovaprim (0.5, 1.0, 1.5 and 2.0 ml/kg body weight) and five latency periods (11, 14, 17, 20 and 23 hr) were considered in 20 different combinations. There were no deformed larvae in the females injected with all four doses and stripped at 11 hr latency, as the eggs did not hatch. The percentage of deformed larvae (4-7%) did not vary significantly at 1.0-2.0 ml dose level in combination with 14-17 hr latency periods. While increasing the latency period beyond 17 hr at 1-1.5 ml dose level, the percentage of deformed larvae increased significantly and touched as high as 11%. The results indicated that 1-1.5 ml dose in combination with 14-17 hr latency are suitable to reduce the deformed larvae among the hatchlings during induced spawning of C. batrachus.

Formalin assay parameters differ in confirming the antinociceptive mechanism of domperidone in mice.

Domperidone, a prokinetic drug with minimal extrapyramidal side-effects was investigated for its antinociceptive response in mice using formalin assay procedure. Two parameters namely the pain score and the time spent by the animal in licking/biting the formalin injected paw were considered. Domperidone (1, 2.5 or 5 mg/kg; ip) injected 15 min prior to formalin effectively reduced the pain score bringing it to zero at the 15th minute and was also effective till 30 min but to a lesser degree. This effect of domperidone (2.5 mg/kg) was significantly attenuated in naloxone pretreated mice indicating a partial role for opioid pathways. In the other parameter i.e. time spent in licking/biting, domperidone in all the doses employed failed to modify significantly the same by the animal in the early phase. In contrast, a dose related inhibition of the time spent was recorded in the late phase. Besides, a trend towards the enhancement of the inhibitory effect of domperidone (2.5 mg/kg) in the late phase was noticed in naloxone pretreated mice. Possibly, the peripheral analgesic mechanisms may play a role in this response since the late phase was considered akin to inflammation. The results confirm the antinociceptive effect of domperidone and suggest that caution be exercised while selecting the parameters when formalin assay is employed.

Effects of chronic domperidone treatment on rat conditioned avoidance behavior

The effects of chronic administration of domperidone (DOM), a peripherally acting anti-emetic and hyperprolactinemic D2-dopaminoceptor antagonisti, on active and inhibitory conditioned behavior were tested on male and female rats. DOM (4 mg/Kg) was injected ip daily either for 5 or 30 days. Although treatment for 5 days failed to effect experimental parameters, treatment for 30 days impaired the performance of active conditioned avoidance of female, but not male, rats. This effect was no longer observed 7 days after ending treatment. No effects of DOM treatment were observed on active conditioned avoidance of male rats or on inhibitory conditioned behavior of all rats. These data suggest that female rats are more susceptible to the hyperprolactinemic effects of DOM than male rats. However, an influence of estrous cycle interruption cannot be rejected

Antidopaminergic effect of oral demperidone on the pituitary gland in normal and hyperprodoctinemia women

La secreción hipofisaria de tirotropina (TSH) y prolactina PRL) en respuesta a deomperidon oral (DOM) fue estudiada en mujeres normales no embarazadas en etapa reproductiva (como grupo control), en mujeres hiperprolactinémicas, lactantes y en pacientes con hiperprolactinemia patológica (HP). Las mujeres normales sin embarazo, recibieron por vía oral placebo (n=5), DOM 10 mg (n=10) o DOM 30 mg (n=10). Las mujeres lactantes (n=20) y las mujeres con HP (n=20) recibieron DOM 10 mg por vía oral. Además a tres pacientes con HP se les administraron 500 ug de TRH i.v. después de terminar la prueba con DOM. La dosis de diez miligramos de DOM indujo una elevación rápida de PRL que fue máxima a los 60 a 120 min en el grupo control, el incremento máximo de PRL (delta PRL) fue de 150.4 ñ 19.4 ug/l y la suma total de los incrementos de PRL fue de 340.3 ñ 54.4 ug/l. cuando se incrementó la dosis de DOM oral a 30 mg se indujo una mayor respuesta de PRL, delta PRL 298 ñ 53.2 ug/l, suma total de los incrementos 673.7 ñ 94.6 ug.l, p < 0.05). Sin embargo, las mujeres puérperas lactantes tuvieron una respuesta variable pero disminuida de PRL y las pacientes cor HP no tuvieron respuesta de PRL al DOM oral. En el grupo control sólo la mitad de las mujeres tuvieron una elevación clara de TSH después de DOM oral, de ellas cinco respondieron a 10 mg y cinco a 30 mg. El incremento máximo de TSH (delta TSH) ocurrió 60 a 120 min después de la ingestión de la droga y no hubo diferencias significativas en el delta TSH, ni en la suma total de los incrementos entre las mujeres que respondieron a 10 mg y 30 mg, delta TSH 1.27 ñ 0.18 mu/1, suma de incrementos 2.82 ñ 1.35 mu/l. La mujeres lactantes notuvieron modificaciones de kis biveles basales de TSH después de DOM, once pacientes con HP tuvieron respuesta de TSH y fueron agrupados separadamente. Los niveles delta TSH fueron significativamente mayores a los 120 min de los obtenidos en mujeres normales en etapa reproductiva con 10 y 30 mg de DOM (p<0.02)...

Gastric cytoprotection induced by prostaglandin-dopaminergic mechanism

Se estudió el efecto citoprotector sobre la mucosa gástrica de la Bromcriptina ante la injuria del etanol absoluto, donde dio citoprotección gástrica similar al Misoprostol. Pretratamiento con SCH 23390 (un antagonista de los receptores dopaminérgicos vasculares periféricos) y Domperidona ( un antagonista de los receptores dopaminérgicos neurales periféricos), mostró que Misoprostol fue dependiente de los receptores dopaminérgicos periféricos en su mecanismo citoprotector; así como Bromocriptina fue un agonista dopaminérgico neuronal periférico en su mecanismo citoprotector. Pretratamiento con Indometacina, mostró que los receptores dopaminérgicos periféricos fueron dependientes de las prostaglandinas endógenas en su mecanismo citoprotector. En conclusión, fue postulado un mecanismo prostaglandino-dopaminérgico periférico en la citoprotección de la mucosa gástrica

Immediate effects of intermitent administration of domperidone upon prolactin release in normal women

El presente, estudio fue llevado a cabo con la finalidad de investigar el efecto de la administración repetida del antagonista dopaminérgico domperidone (DOM) sobre la secreción de prolactina, así como la respuestas de esta hormona a la administración de la hormona liberadora de tirotrofina (TRH) durante el efecto máximo del antagonista. Se estudiaron 9 mujeres normales durante la fase folicular del ciclo menstrual, las cuales fueron divididas en 3 grupos de acuerdo al siguiente diseño: I. Administración repetida de DOM (10 mg cada 60 minutos por 3 horas), seguida de un bolo i.v. de TRH (200 ug). II. Bolos intermitentes de DOM (10 mg cada 60 minutos por 2 horas), seguidos de TRH, 200 ug. i.v. al tiempo de la tercera inyección del DOM, y III. Bolos intermitentes de DOM (10 mg/hora por 3 horas), seguidas de 10 mg i.v. de metoclopramida al momento de la última dosis de DOM, así como de 200 g de TRH administrados 90 minutos después del bolo de DOM + metoclopramida. Las concentraciones plasmáticas de PRL inmunorreactiva fueron cuantificados antes y a intervalos de 15 a 30 minutos durante los experimentos. Treinta minutos después del primer bolo de DOM, todos los sujetos mostraron un incremento significativo en las concentraciones séricas de prolactina (PRL); posteriormente, dichas concentraciones disminuyeron progresivamente a pesar de bolos adicionales del antagonista. Igualmente, la administración de metoclopramida al tiempo de la refractariedad hipofisiaria al DOM, fue incapaz de incrementar las concentraciones séricas de PRL. Todos los sujetos respondieron a TRH sin importar el momento de la inyección, las concentraciones séricas de PRL presentes o las manipulaciones farmacológicas precedentes (administración de DOM y/o metoclopramida). La cinética de liberación de PRL durante estas manipulaciones farmacológicas pudieran ser explicadas por el efecto agonista-antagonista del DOM sobre la secreción del lactotropo. Más aún, la presencia de una respuesta a significativa a TRH durante períodos de refractariedad al DOM, sugiere la existencia de 2 pozas de PRL en el lactotropo humano, una de ellas regulada por dopamina en tanto que la segunda por un factor liberador de PRL y/o por TRH