RESUMEN
The coumarins 5-methoxy-6,7-methylenedioxycoumarin 1 5-(3-methyl-2-butenyloxy)-6,7-methylenedioxycoumarin 2 and 5-(2,3-dihydroxy-3-methylbutyloxy)-6,7-methylenedioxycoumarin 3 isolated from Pterocaulon species showed significant cytotoxicity against two glioma cells lines. Compound 1 presented IC(50) values of 34.6 µM and 31.6 µM against human (U138-MG) and rat (C6) glioma cells, respectively, and this compound was at least two times more potent than compounds 2 and 3. This result could be explained by the planar conformation adopted by 1 through a non-classical hydrogen bond between a hydrogen of the methoxy and the oxygen of the methylenedioxy groups. Another important finding was that the cytotoxic effect induced by 1 in glioma cells was not observed in organotypic cultures, indicating a selective cytotoxicity for tumor cells.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Apoptosis/efectos de los fármacos , Asteraceae/química , Benzodioxoles/aislamiento & purificación , Cumarinas/aislamiento & purificación , Citotoxinas/aislamiento & purificación , Animales , Antineoplásicos/farmacología , Benzodioxoles/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/patología , Cumarinas/farmacología , Citotoxinas/farmacología , Glioma/tratamiento farmacológico , Glioma/patología , Hipocampo/citología , Hipocampo/efectos de los fármacos , Humanos , Enlace de Hidrógeno , Concentración 50 Inhibidora , Masculino , Especificidad de Órganos , Ratas , Ratas Wistar , Relación Estructura-Actividad , Técnicas de Cultivo de TejidosRESUMEN
The vacuolar proton pump (V-ATPase) located on the plasma membrane of the osteoclast is a potential molecular target for the discovery of novel bone antiresorptive agents useful for the treatment of osteoporosis. In order to design novel compounds able to selectively inhibit the osteoclast V-ATPase we firstly identified the minimal structural requirements of bafilomycin A1, a macrolide antibiotic which potently inhibits all V-ATPases. This information allowed the design of 2-(indole)pentadienamide derivatives whose optimization led to a novel class of potent inhibitors that demonstrated a high degree of selectivity for the osteoclast V-ATPase. The most interesting derivative, SB-242784, was able to inhibit bone resorption by human osteoclasts in vitro and to completely prevent ovariectomy-induced bone loss in rats when administered orally at 10 mg kg(-1) day(-1). Structure activity relationships of this class of compounds were investigated further by replacing the 2,4-pentadienoyl chain with suitable spacers able to maintain the correct orientation and distance between the indole ring and the amide moiety.
Asunto(s)
Resorción Ósea/prevención & control , Inhibidores Enzimáticos/farmacología , Osteoclastos/efectos de los fármacos , ATPasas de Translocación de Protón/antagonistas & inhibidores , ATPasas de Translocación de Protón Vacuolares , Animales , Humanos , Osteoclastos/enzimología , Osteoporosis/prevención & control , Relación Estructura-ActividadRESUMEN
A potent and selective inhibitor of the osteoclastic V-H(+)-ATPase, (2Z,4E)-5-(5,6-dichloro-2-indolyl)-2-methoxy-N-(1,2,2,6, 6-pentamethylpiperidin-4-yl)-2,4-pentadienamide (SB 242784), was evaluated in two animal models of bone resorption. SB 242784 completely prevented retinoid-induced hypercalcemia in thyroparathyroidectomized (TPTX) rats when administered orally at 10 mg/kg. SB 242784 was highly efficacious in the prevention of ovariectomy-induced bone loss in the rat when administered orally for 6 months at 10 mg/kg/d and was partially effective at 5 mg/kg/d. Its activity was demonstrated by measurement of bone mineral density (BMD), biochemical markers of bone resorption, and histomorphometry. SB 242784 was at least as effective in preventing bone loss as an optimal dose of estrogen. There were no adverse effects of compound administration and no effects on kidney function or urinary acidity. Selectivity of the inhibitor was further studied using an in situ cytochemical assay for bafilomycin-sensitive V-H(+)-ATPase using sections of osteoclastoma and numerous other tissues. SB 242784 inhibited the osteoclast enzyme at 1,000-fold lower concentrations than enzymes in any of the other tissues evaluated. SB 242784 demonstrates the utility of selective inhibition of the osteoclast V-H(+)-ATPase as a novel approach to the prevention of bone loss in humans.
Asunto(s)
Resorción Ósea/tratamiento farmacológico , Indoles/uso terapéutico , Osteoclastos/enzimología , Osteoporosis/tratamiento farmacológico , Piperidinas/uso terapéutico , ATPasas de Translocación de Protón/antagonistas & inhibidores , ATPasas de Translocación de Protón Vacuolares , Vacuolas/enzimología , Ácidos/análisis , Administración Oral , Animales , Benzoatos/farmacología , Densidad Ósea , Interacciones Farmacológicas , Inhibidores Enzimáticos/uso terapéutico , Estradiol/farmacología , Femenino , Fémur/patología , Hipercalcemia/tratamiento farmacológico , Región Lumbosacra , Osteoclastos/efectos de los fármacos , Ovariectomía , Paratiroidectomía , Ratas , Ratas Sprague-Dawley , Retinoides/farmacología , Columna Vertebral/patología , Tiroidectomía , Orina/química , Vacuolas/efectos de los fármacosRESUMEN
Aim of this study is to compare traditional post-partum hospital stay to hospitalization associated with early protected discharge: a case-control study has been performed to evaluate outcome as mother's appreciation of the experience as well as breastfeeding. The study included 50 healthy-term newborns and their mothers, discharged within 24 and 48 hours of life, and 44 controls, who had traditional "rooming-in" stay, delivered at the Department of Neonatology--University of Turin. The protocol included a midwife daily home visits and a neonatologist and nurse visit within 4th to 5th day of life, to evaluate mother's and baby's health status and to perform metabolic screenings. An ambulatorial follow-up visit at 1 month of life and 2 telephone interviews, at 3rd and 6th month, were also planned. During the first week of life 45 (90%) early discharged newborns had complete nursing (breastfeeding + water or other fluids), 4 (8%) had complementary nursing (breastfeeding + formula) and 1 (2%) received formula. Among controls, 46 (92%) babies received complete nursing, 2 had complementary nursing and 2 had artificial nursing. At 6 months of life breastfeeding was complete for 2% of cases and 6% of controls; in 44% of cases and 56% of controls nursing was complementary. Readmissions to our Birth Center were 2 among early discharged newborns, 1 in the control group. About project's appreciation, 96% of early discharged and 98% of control group mothers declared their availability to repeat the experience. Caring and supporting were judged adequate in 94% of both group. By adequate supporting of mother and newborn, short and traditional hospitalization are both pleasant and don't seem to present significant differences in type and length of nursing.
Asunto(s)
Tiempo de Internación/estadística & datos numéricos , Alta del Paciente/estadística & datos numéricos , Lactancia Materna/estadística & datos numéricos , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Recién Nacido , Italia , Proyectos Piloto , Estudios Prospectivos , Factores de TiempoRESUMEN
This paper describes the design and synthesis of compounds belonging to a novel class of substituted pyrrolooctahydroisoquinolines which are potent and selective delta opioid agonists. Molecular modeling studies performed on known, selective delta ligands such as (+)-3 and the potent delta agonists SNC 80 led to the identification of the carboxamido moiety of the latter as a putative nonaromatic delta address. Insertion of this moiety onto the octahydroisoquinoline opioid message resulted in (+/-)-5b, a potent and selective delta ligand. The active enantiomer, (-)-5b, displayed nanomolar affinity for the delta receptor (Ki = 0.9 nM) with good mu/delta and kappa/delta binding selectivity ratios (140 and 1480, respectively). In addition, (-)-5b behaved as a full delta agonist in the mouse vas deferens bioassay having an IC50 = 25 nM and being antagonised in the presence of 30 nM naltrindole (NTI). These studies, based on the message-address concept, indicated that the nonaromatic (N,N-diethylamino)carbonyl moiety is a viable alternative to the classical benzene ring as a delta opioid address. Preliminary in vivo studies showed that (+/-)-5b produced a dose-related antinociception in the mouse abdominal constriction test after intracerebroventricular administration (ED50 = 1.6 micrograms/mouse).
Asunto(s)
Indoles/química , Isoquinolinas/química , Pirroles/química , Receptores Opioides delta/agonistas , Animales , Benzamidas/química , Benzamidas/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Simulación por Computador , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Leucina Encefalina-2-Alanina/metabolismo , Indoles/farmacología , Isoquinolinas/farmacología , Ligandos , Masculino , Ratones , Modelos Moleculares , Naltrexona/análogos & derivados , Naltrexona/farmacología , Antagonistas de Narcóticos/farmacología , Nociceptores/efectos de los fármacos , Piperazinas/química , Piperazinas/farmacología , Pirroles/farmacología , Quinolinas/química , Quinolinas/metabolismo , Transducción de Señal , Estereoisomerismo , Conducto Deferente/efectos de los fármacosRESUMEN
Fetal death incidence is 5-10 per 1,000 births. About 25% of the women who carry a dead fetus for more than 4 weeks will show significant alterations in their coagulation system. The treatment for a patient with endouterine fetal death depends on when the pregnancy is terminated, based on the ecographic fetus age. There were 15,070 births from January 1983 to December 1994 in Department B of the Institute of Obstetrics and Gynecology, University of Torino. We took into consideration the cases ofintrauterine fetal death between the 26th and 40th week before labour. This study is based on a cohort of 57 cases of intrauterine fetal demise from the 24th to the 40th week of pregnancy before spontaneous labour.
Asunto(s)
Aborto Terapéutico , Muerte Fetal , Aborto Terapéutico/métodos , Cesárea , Dilatación y Legrado Uterino , Femenino , Humanos , Trabajo de Parto Inducido/métodos , Embarazo , Segundo Trimestre del Embarazo , Tercer Trimestre del EmbarazoRESUMEN
Eighty-five breast cancer patients who had been operated for mastectomy and were currently undergoing adjuvant or therapeutic chemotherapy were included in the study. Patients were divided into two matching groups of 50 (A) and 35 (B) subjects; group A was treated with CT and thymostimulin Serono and group B with CT alone. The difference between the two groups in relation to first-degree (24% vs 57%) and second-degree leucopenia (8% vs 14%), in addition to the difference in relation to infections and the regularity of chemotherapy cycles confirmed the value of immunotherapy with thymostimulin during chemotherapy for breast cancer.
Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/cirugía , Complicaciones Posoperatorias/prevención & control , Extractos del Timo/uso terapéutico , Terapia Combinada , Método Doble Ciego , Femenino , Humanos , Mastectomía , Infección de la Herida Quirúrgica/prevención & controlRESUMEN
Antibiotic prophylaxis reduces the incidence of infections after some types of surgical interventions; in Obstetrics it can prevent infections in high risk situations. Infections can occur in particular situations, even in cesarean sections (CS) at low risk. The incidence of puerperal endometritis is variable in literature, while the incidence of pelvic or surgical wound infections is 3.8% in elective CS with respect to 7.5% in emergency CS. This study verifies the efficacy of the sulbactam-ampicillin association (Unasyn, Pfizer) in the prophylaxis of all cesarean sections, complicated or not. Unasyn was administrated one hour prior to CS and 8 and 16 hours after CS in 162 patients. Therapy was continued in 8 cases because of high risk for infection. The evaluation of the efficacy of the drug was based on clinical criteria. There were no complications or fever recorded and no toxic or allergic reactions occurred. Antibiotic prophylaxis is recommended for all patients undergoing CS.
Asunto(s)
Ampicilina/administración & dosificación , Infección Puerperal/prevención & control , Sulbactam/administración & dosificación , Infección de la Herida Quirúrgica/prevención & control , Adulto , Cesárea/efectos adversos , Quimioterapia Combinada , Endometritis/prevención & control , Femenino , HumanosAsunto(s)
Padres/educación , Convulsiones Febriles/enfermería , Niño , Preescolar , Humanos , Lactante , Recurrencia , Convulsiones Febriles/psicologíaAsunto(s)
Maltrato a los Niños/diagnóstico , Niño , Abuso Sexual Infantil/diagnóstico , Defensa del Niño , Femenino , Humanos , Lactante , MasculinoRESUMEN
Three hundred and sixty patients underwent hysteroscopy before entering the IVF program. The procedure was successful in 332 patients; obstructive tubal disease was present in 247 (70%); 148 showed uterine abnormalities (44.5%) such as endometrial polyps, adhesions, hypoplasia, malformations, or severe cervical stenosis; 114 patients had normal hysterographic findings, in whom hysteroscopy revealed a false-negative rate of 36.8%. In 281 patients (84.6%) hysteroscopy was carried out under general anesthesia, in most cases associated with laparoscopy. There were no anesthetic complications, uterine perforations or other significant problems. In an IVF program, hysteroscopic evaluation can reduce the failure rate due to intra-uterine abnormalities. Hysteroscopy, which permits one to optimize an IVF attempt, becomes an essential procedure before introducing a patient into an IVF program.
Asunto(s)
Fertilización In Vitro , Infertilidad Femenina/patología , Útero/patología , Adulto , Endoscopía , Femenino , Humanos , Enfermedades Uterinas/patología , Útero/anomalíasRESUMEN
Rabies was first reported by Aristotle over 2,000 years ago and has plagued man ever since. Little has been done to provide adequate treatment once the symptoms have appeared. Therefore the battle against rabies involves health education and prophylaxis, although during the incubation period rabies is treatable. The incubation period of this communicable disease can range from ten days to six months but may be as long as two years. The length of the incubation period is determined by the proximity and severity of the bite, to the brain.
RESUMEN
Evidence is presented to indicate that a PvuII fragment of approx. 2 kb isolated from the 39-kb IncN-group plasmid pCU-1 contains all plasmid-borne determinants for stable maintenance as an extrachromosomal element in Escherichia coli K-12. The fragment was sequenced. The features of this sequence include a group of 13 direct tandem repeats of 37 bp and a second group of two other direct repeats of 30 bp flanking a third partial member of this group. In addition, for a 19-bp sequence that overlaps a member of this second group, there are inverted repeats that straddle the members of the first group. There are three open reading frames within the fragment. We compare features of this sequence with that of other plasmid replicons and draw attention to similar and to dissimilar features.