ABSTRACT
Neuronal (N)-type Ca(2+) channel-selective omega-conotoxins have emerged as potential new drugs for the treatment of chronic pain. In this study, two new omega-conotoxins, CVIE and CVIF, were discovered from a Conus catus cDNA library. Both conopeptides potently displaced (125)I-GVIA binding to rat brain membranes. In Xenopus laevis oocytes, CVIE and CVIF potently and selectively inhibited depolarization-activated Ba(2+) currents through recombinant N-type (alpha1(B-b)/alpha(2)delta1/beta(3)) Ca(2+) channels. Recovery from block increased with membrane hyperpolarization, indicating that CVIE and CVIF have a higher affinity for channels in the inactivated state. The link between inactivation and the reversibility of omega-conotoxin action was investigated by creating molecular diversity in beta subunits: N-type channels with beta(2a) subunits almost completely recovered from CVIE or CVIF block, whereas those with beta(3) subunits exhibited weak recovery, suggesting that reversibility of the omega-conotoxin block may depend on the type of beta-subunit isoform. In rat dorsal root ganglion sensory neurons, neither peptide had an effect on low-voltage-activated T-type channels but potently and selectively inhibited high voltage-activated N-type Ca(2+) channels in a voltage-dependent manner. In rat spinal cord slices, both peptides reversibly inhibited excitatory monosynaptic transmission between primary afferents and dorsal horn superficial lamina neurons. Homology models of CVIE and CVIF suggest that omega-conotoxin/voltage-gated Ca(2+) channel interaction is dominated by ionic/electrostatic interactions. In the rat partial sciatic nerve ligation model of neuropathic pain, CVIE and CVIF (1 nM) significantly reduced allodynic behavior. These N-type Ca(2+) channel-selective omega-conotoxins are therefore useful as neurophysiological tools and as potential therapeutic agents to inhibit nociceptive pain pathways.
Subject(s)
Analgesics, Non-Narcotic/pharmacology , Calcium Channel Blockers/pharmacology , Calcium Channels, N-Type/metabolism , Recombinant Proteins/antagonists & inhibitors , omega-Conotoxins/pharmacology , Amino Acid Sequence , Analgesics, Non-Narcotic/chemistry , Analgesics, Non-Narcotic/isolation & purification , Animals , Calcium Channel Blockers/chemistry , Calcium Channel Blockers/isolation & purification , Calcium Channels, N-Type/physiology , Cells, Cultured , Conus Snail , Dose-Response Relationship, Drug , Female , Ganglia, Spinal/drug effects , Ganglia, Spinal/physiology , Male , Molecular Sequence Data , Patch-Clamp Techniques , Protein Structure, Tertiary , Rabbits , Rats , Rats, Sprague-Dawley , Rats, Wistar , Recombinant Proteins/genetics , Xenopus laevis , omega-Conotoxins/chemistry , omega-Conotoxins/isolation & purificationABSTRACT
Gastric outlet obstruction is either a late event in the natural history of bilio-pancreatic tumors or the result of recurrent gastric or pancreatic tumors. Self-expansible metal stents, inserted under endoscopic and fluoroscopic control, can be used for palliative treatment. The present study was aimed at evaluating both the feasibility and the results of stenting in patients with malignant gastric outlet obstruction; in addition, some technical suggestions are presented. A total of 33 patients, who had a metal stent positioned, were retrospectively evaluated; 20 of them were women and 13 were men, aged from 45 to 94 years, with a mean age of 75 years. Twenty-seven patients had a pancreatic adenocarcinoma, 4 had a stricture of a gastrojejunal anastomosis due to recurrent pancreatic tumor, 2 had a stricture of a gastrojejunal anastomosis secondary to gastric cancer surgery. No postoperatory complications were observed. Improvement in the quality of life was obtained in all patients. Following the stenting procedure, the median duration of hospitalization was 8 days (range: 6-20 days), and the mean survival rate was 12 weeks (range: 2-66 weeks). Endoscopic stenting for the palliation of malignant gastric outlet obstruction is feasible and is well tolerated by most patients. In some cases a period of enteral nutrition had to be necessarily carried out; nonetheless, the insertion of the stent improved the quality of life.
Subject(s)
Gastric Outlet Obstruction/therapy , Gastroscopy , Palliative Care , Stents , Aged , Aged, 80 and over , Female , Gastric Outlet Obstruction/etiology , Gastric Outlet Obstruction/mortality , Humans , Length of Stay , Male , Metals , Middle Aged , Pancreatic Neoplasms/complications , Quality of Life , Retrospective Studies , Stomach Neoplasms/complications , Survival RateABSTRACT
Se presenta la experiencia en el manejo de pacientes altamente sensibilizadas por incompatibilidad Rh, analizando la utilidad de la evaluación de la velocidad circulatoria fetal, por Doppler-color, a través de la medición de la velocidad máxima sistólica (VMS) de la arteria cerebral media (ACM). Se realizan 19 transfusiones intravasculares en 3 casos afectados por esta enfermedad. En 14 de ellas se encontró anemia fetal moderada o leve, la que fue diagnosticada correctamente en 13 oportunidades, (92,8 por ciento) por la medición anteriormente señalada. Se encuentra una adecuada correlación entre la velocidad máxima sistólica de la arteria cerebral media y el grado de anemia fetal moderada o severa, con un índice correlacional (r= (_) 0,78). Se destaca el beneficio de un método no invasivo en el manejo de la anemia fetal de causa inmunológica o asociada a otras condiciones mórbidas y se abre un campo para futuras investigaciones.
Subject(s)
Female , Pregnancy , Anemia, Hemolytic/etiology , Anemia, Hemolytic/therapy , Fetal Diseases , Rh Isoimmunization/complications , Rh Isoimmunization/therapy , Middle Cerebral Artery , Ultrasonography, Doppler, Color , Pregnancy ComplicationsABSTRACT
Se define hidrops fetal como la acumulación anormal de líquido en piel (edema) y en cavidades corporales (derrame pericárdico, pleural o ascitis). La prevalencia de esta patología es de alrededor de 1 por 200 nacimientos. Las causas pueden ser fetales (cardiológicas, hematológicas, cromosómicas, infecciosas, etc.) como maternas. Clásicamente se divide en inmune (hemólisis fetal por anticuerpos maternos) y no inmune (todas las demás etiologías). La mortalidad general, sin tratamiento es de alrededor de un 80 por ciento. El propósito de este trabajo es presentar la experiencia de los casos de hidrops fetal diagnosticados en la Unidad de Ultrasonografía del Hospital Clínico San Borja Arriarán, Santiago, Chile, en un período de 15 meses desde 1 de enero 2001 al 31 marzo 2002, en donde se evaluó diagnóstico prenanatal, manejo perinatológico, vía del parto y resultado perinatal. Se evaluaron un total de nueve casos, dos de causa inmune (22 por ciento) y siete de causa no inmune (78 por ciento). Los casos de causa inmune correspondieron a isoinmunización Rh y presentaron una sobrevida de un 100 por ciento. Los casos no inmunológicos presentaron un 33 por cientoü cromosopatías, 22² alteraciones hematológicas, un 11 por ciento de causa cardiológica y 11 por cientoû de causa idiopática. La sobrevida de este grupo fue de un 22 por ciento²
