RESUMEN
The usefulness of iontophoresis is restricted to highly water-soluble compounds, since drugs are generally applied as an aqueous solution in a drug electrode. In the present study, salicylic acid (SA) dissolved in ethanol-water mixture was loaded in a drug electrode, and the effect of ethanol on the iontophoretic transdermal delivery of SA was evaluated. Ethanol at a concentration of 10 or 30% showed no significant effect on the iontophoretic transdermal delivery of SA compared to that in the absence of ethanol, but 40 or 70% ethanol increased it significantly. The current density passing through in vivo during iontophoretic treatment decreased with increase in ethanol concentrations. These results suggested that the enhanced transdermal absorption of SA iontophoretically by the presence of ethanol in a drug solution is not due to the increased current density in vivo, but probably due to the direct action of ethanol on the stratum corneum. In conclusion, addition of ethanol to a drug solution at an appropriate concentration was proved to enhance the iontophoretic transdermal delivery of SA. A mixture of ethanol and water can dissolve many poorly water-soluble drugs, and therefore it would be able to expand the application of iontophoresis to include many drugs that are poorly soluble in water.
Asunto(s)
Ácido Salicílico/administración & dosificación , Administración Cutánea , Animales , Etanol , Concentración de Iones de Hidrógeno , Iontoforesis , Masculino , Soluciones Farmacéuticas , Ratas , Ratas Wistar , Solventes , AguaRESUMEN
A 48-year-old female presented with acromegaly, amenorrhea and hyperthyroidism associated with high serum free T4 levels and measurable TSH concentrations. The administration of GHRH induced significant increases in GH, PRL and TSH. Conversely, intravenous infusion of dopamine or oral administration of bromocriptine effectively inhibited GH, PRL and TSH secretion. Serum alpha-subunit levels were neither affected by GHRH, dopamine nor bromocriptine. Transsphenoidal surgery was performed and immunostaining of the tissue showed that the adenoma cells were positive for GH, PRL or TSH. The patient was treated with bromocriptine at a daily oral dose of 10 mg after surgery. Serum TSH were initially suppressed but returned within reference intervals with persistent normalized free T4 levels. Serum PRL became undetectable and GH levels were stable around 6 ng/ml except the periods of poor drug compliance, when serum TSH, GH and PRL levels rose considerably. The patient was followed-up for 10 years without any change in the residual adenoma tissues as detected by magnetic resonance imaging. These findings suggest that long-term bromocriptine therapy is effective in treating the hypersecretory state of a plurihormonal adenoma secreting TSH, GH and PRL.
Asunto(s)
Adenoma/metabolismo , Bromocriptina/uso terapéutico , Hormona de Crecimiento Humana/metabolismo , Neoplasias Hipofisarias/metabolismo , Prolactina/metabolismo , Tirotropina/metabolismo , Acromegalia/etiología , Adenoma/diagnóstico , Adenoma/tratamiento farmacológico , Amenorrea/etiología , Bromocriptina/administración & dosificación , Femenino , Hormona Liberadora de Hormona del Crecimiento , Antagonistas de Hormonas/administración & dosificación , Antagonistas de Hormonas/uso terapéutico , Humanos , Hipertiroidismo/etiología , Persona de Mediana Edad , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/tratamiento farmacológico , Valores de Referencia , Hormona Liberadora de Tirotropina , Tiroxina/sangreRESUMEN
To elucidate the role of calcitonin gene-related peptide (CGRP) in regulating pituitary function, we investigated the effects of CGRP and the related peptide adrenomedullin (AdM) on the secretion of growth hormone (GH) in vitro from human pituitary adenoma cells, rat pituitary tumor (GH3) cells, and normal rat pituitary cells. In 3 of 5 human somatotroph adenomas, GH secretion was stimulated by CGRP (1-100 nM). In one case of somatotroph adenoma, GH release was observed following the addition of 10 nM GHRH and 10 nM CGRP. The addition of CGRP or AdM (1 pM-10 nM) evoked GH secretion from GH3 cells with a bell-shaped distribution curve. CGRP (100 pM) caused the maximum increase of GH secretion (172+/-14 (mean+/-S.D.)% of control). The addition of CGRP8-37, an antagonist of CGRP type 1 receptors, inhibited the stimulatory effect of AdM but did not inhibit the effect of CGRP. The addition of CGRP and AdM evoked moderate GH secretion from normal rat pituitary cells. These results suggested that CGRP is a new GH secretagogue in human and rat pituitary tumor cells.
Asunto(s)
Péptido Relacionado con Gen de Calcitonina/fisiología , Hormona del Crecimiento/metabolismo , Hormona de Crecimiento Humana/metabolismo , Péptidos/farmacología , Hipófisis/efectos de los fármacos , Adenoma/metabolismo , Adenoma/patología , Adrenomedulina , Animales , Péptido Relacionado con Gen de Calcitonina/farmacología , Humanos , Hipófisis/metabolismo , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/patología , Ratas , Células Tumorales CultivadasAsunto(s)
Péptido Relacionado con Gen de Calcitonina/farmacología , Hormona del Crecimiento/metabolismo , Animales , Péptido Relacionado con Gen de Calcitonina/administración & dosificación , Relación Dosis-Respuesta a Droga , Hormona de Crecimiento Humana/metabolismo , Humanos , Neoplasias Hipofisarias/metabolismo , Ratas , Células Tumorales CultivadasRESUMEN
McCune-Albright syndrome (MAS) is clinically characterized by polyostotic fibrous dysplasia, cafe au lait pigmentation of the skin and multiple endocrinopathies. Recently activating mutations of codon 201 in the gene encoding Gs alpha have been found in affected tissues in MAS. Herein we report a case of acromegaly associated with multiple bone cysts and skin pigmentation in a 47-year-old women. She had suffered a history of aortitis syndrome. The DNA sequence indicated that a Cys201 for Arg201 substitution was found in the GH secreting pituitary adenoma tissue but not in peripheral mononuclear cells. We speculate that the patient has a possible variant from of MAS characterized by multiple bone lesions skin pigmentation and GH-secreting pituitary adenoma.
Asunto(s)
Adenoma/complicaciones , Síndromes del Arco Aórtico/complicaciones , Displasia Fibrosa Poliostótica/complicaciones , Neoplasias Hipofisarias/complicaciones , Adenoma/genética , Adenoma/metabolismo , Secuencia de Bases , ADN/química , Femenino , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Hormona de Crecimiento Humana/metabolismo , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Mutación , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/metabolismo , Análisis de Secuencia de ADN , Tomografía Computarizada por Rayos XAsunto(s)
Acromegalia/sangre , Hormona de Crecimiento Humana/deficiencia , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor II del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Ensayo Inmunorradiométrico , Persona de Mediana EdadRESUMEN
The expression of somatostatin receptor (SSTR) subtypes and relative abundance of SSTR2 mRNA were examined in 18 pituitary adenomas using the reverse transcription-polymerase chain reaction (RT-PCR) method. SSTR1 and SSTR2 were expressed in all pituitary adenomas examined. Six of 9 somatotroph adenomas, 1 of 4 lactotroph adenomas and 1 of 2 thyrotroph adenomas also expressed SSTR5. SSTR3 and SSTR4 mRNAs were detected in 1 and 2 cases of somatotroph adenoma, respectively. SSTR2 mRNA expression was quantified by comparison with the PCR cycle-dependent amplification of beta-actin or cyclophilin. The relative abundance of SSTR2 mRNA varied greatly among adenomas with more than a 1000-fold difference. SSTR2 mRNAs in lactotroph adenomas were less abundant (P < 0.01) than those in somatotroph adenomas. No significant correlation was found between the relative abundance of SSTR2 mRNA levels and GH sensitivity to octreotide administration. However, one of the thyrotroph adenomas exhibited marked shrinkage in tumor size after octreotide therapy, in which SSTR2 mRNA was the most abundant among the adenomas examined. GH sensitivity to octreotide was not significantly different between SSTR5 mRNA positive and negative adenomas. In conclusion, SSTR2 mRNA levels varied greatly among pituitary adenomas but were not correlated with GH sensitivity to octreotide. Further investigations of functional SSTR subtype proteins and of postreceptor signal transductions are required to clarify the molecular mechanisms of octreotide action.
Asunto(s)
Adenoma/metabolismo , Neoplasias Hipofisarias/metabolismo , Reacción en Cadena de la Polimerasa/métodos , ARN Mensajero/análisis , Receptores de Somatostatina/genética , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadística como Asunto , Transcripción GenéticaRESUMEN
The expression of neurotrophin-3 (NT-3) in skeletal muscles was measured in rats with streptozotocin (STZ)-induced diabetes using Northern blot analysis. At 6 weeks after STZ induction of diabetes, the NT-3 mRNA level in the quadriceps and gastrocnemius muscles was decreased by 45 and 77%, respectively, compared with that in age-matched controls. Since NT-3 is considered to be essential for the maintenance of spinal proprioceptive afferent neurons, decreased NT-3 expression in target tissues would impair the integrity of afferent neurons and might be an earlier marker in the sensory neuronal damage observed in diabetes mellitus.
Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Músculo Esquelético/metabolismo , Factores de Crecimiento Nervioso/biosíntesis , Animales , Regulación hacia Abajo , Masculino , Neurotrofina 3 , Ratas , Ratas Wistar , Regulación hacia ArribaRESUMEN
We report a rare case of ectopic ACTH syndrome associated with undifferentiated carcinoma of the ascending colon. A 62-year-old woman developed hypokalaemia and metabolic alkalosis associated with markedly elevated serum cortisol and plasma ACTH levels. High-dose dexamethasone (8 mg/day) did not suppress increased urinary 17-hydroxycorticosteroid and 17-keto-steroid excretion. Barium enema and abdominal computerised tomography showed a Borrmann II type tumour in the ascending colon, multiple metastatic nodules in the liver and bilateral enlargement of the adrenal glands. Histological examination of the resected primary colon cancer and metastatic liver tumour showed undifferentiated carcinoma with areas of distinct neuroendocrine, exocrine, and squamous differentiation. ACTH production by the tumour was confirmed by radioimmunoassay and immunohistochemistry. This is a unique case report of carcinoma of the colon with distinct multidirectional differentiation causing ectopic ACTH syndrome.
Asunto(s)
Síndrome de ACTH Ectópico/patología , Carcinoma/patología , Neoplasias del Colon/patología , Carcinoma/química , Diferenciación Celular , Neoplasias del Colon/química , Epitelio/patología , Glándulas Exocrinas/patología , Femenino , Humanos , Persona de Mediana Edad , Tumores Neuroendocrinos/patologíaAsunto(s)
Glándulas Suprarrenales/fisiología , Médula Espinal/fisiología , Sustancia P/farmacología , Hormona Liberadora de Tirotropina/farmacología , Glándulas Suprarrenales/irrigación sanguínea , Glándulas Suprarrenales/efectos de los fármacos , Animales , Compuestos de Bifenilo/administración & dosificación , Compuestos de Bifenilo/farmacología , Glucemia/metabolismo , Epinefrina/sangre , Inyecciones Espinales , Masculino , Antagonistas del Receptor de Neuroquinina-1 , Ratas , Ratas Wistar , Receptores de Neuroquinina-1/fisiología , Valores de Referencia , Médula Espinal/efectos de los fármacos , Sustancia P/administración & dosificación , Hormona Liberadora de Tirotropina/administración & dosificaciónRESUMEN
Intracerebroventricular administration of galanin (GAL) potently evoked growth hormone (GH) secretion in conscious male rats. Pretreatments with neostigmine and cysteamine blunted the GAL-induced GH secretion. Pretreatment of animals with a specific anti-somatostatin serum significantly inhibited the GAL-induced GH secretion. On the contrary, GH-releasing hormone-induced GH secretion was significantly enhanced with cysteamine and anti-somatostatin serum. These results suggest that somatostatin is involved in GAL-induced GH secretion in rats.
Asunto(s)
Hormona del Crecimiento/metabolismo , Péptidos/farmacología , Somatostatina/fisiología , Animales , Cisteamina/farmacología , Galanina , Inyecciones Intraventriculares , Masculino , Neostigmina/farmacología , Péptidos/administración & dosificación , Péptidos/antagonistas & inhibidores , Ratas , Ratas WistarAsunto(s)
Síndrome de Silla Turca Vacía/etiología , Atrofia , Síndrome de Silla Turca Vacía/diagnóstico , Síndrome de Silla Turca Vacía/terapia , Femenino , Humanos , Hipertrofia , Imagen por Resonancia Magnética , Masculino , Pruebas de Función Hipofisaria , Hipófisis/anomalías , Hipófisis/patología , Estándares de Referencia , Tomografía Computarizada por Rayos XRESUMEN
A 33-year-old man with hypopituitarism is documented. He was born at breech presentation without asphyxia. He was the shortest in his class throughout his school days. He kept slowly growing and reached 172.8 cm at the age of 33. He was devoid of secondary sexual characteristics. Endocrinological studies showed panhypopituitarism with elevated levels of plasma TSH (15.0 microU/ml). TRH administration resulted in a marked increase in plasma TSH. Posterior pituitary function was normal. MR imaging showed transection of the pituitary stalk and the presence of ectopic and eutopic posterior lobes. The replacement of corticosteroid was initiated, and exaggerated response of TSH to TRH disappeared. Delayed bone maturation due to hypogonadism and hypothyroidism was one of the reasons why he had normal height without GH therapy. The significance of his peculiar MRI findings remains to be determined.