RESUMEN
AIM: The study aimed to evaluate the current risk factors for severe perineal tears in a single university-affiliated maternity hospital. METHOD: An obstetric database of 31 784 consecutive women who delivered from January 2007 to December 2009 was screened for cases of third-degree or fourth-degree perineal tears. Four controls, matched by time of delivery, were selected for each case of third- or fourth-degree perineal tear. Maternal and obstetric parameters were analyzed and compared between the study and control groups. RESULTS: Sixty women (0.25% of all vaginal deliveries) had a third-degree (53 women) or a fourth-degree (seven women) perineal tear. The control group comprised 240 matched vaginal deliveries without severe tears. Primiparity, younger maternal age, Asian ethnicity, longer duration of second stage of labour, vacuum-assisted delivery and heavier newborn birth weight were significantly more common among women who had third- or fourth-degree perineal tears. Of the variables that were found to be statistically significant in the univariate analysis, only primiparity (OR = 2.809, 95% CI: 1.336-5.905), vacuum delivery (OR = 10.104, 95% CI: 3.542-28.827) and heavier newborn birth weight (OR = 1.002, 95% CI: 1.001-1.003) were found to be statistically significant independent risk factors for severe perineal trauma. CONCLUSION: Identification of women at risk may facilitate the use, or avoidance, of certain obstetric interventions to minimize the occurrence of childbirth-associated perineal trauma.
Asunto(s)
Peso al Nacer , Laceraciones/etiología , Perineo/lesiones , Extracción Obstétrica por Aspiración/efectos adversos , Adulto , Pueblo Asiatico , Estudios de Casos y Controles , Femenino , Humanos , Segundo Periodo del Trabajo de Parto , Laceraciones/etnología , Edad Materna , Complicaciones del Trabajo de Parto/etnología , Paridad , Parto , Embarazo , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
Processing of beta-amyloid precursor protein (APP) is coupled to several neurotransmitter receptors, including m1 muscarinic (m1AChR), and is associated with decreased amyloid deposition. Muscarinic agonist-stimulated APP secretion and membrane APP were measured in control and in NGF-differentiated PC12 cells stably transfected with m1AChR. This secretion was markedly enhanced following treatment with 50 ng/ml NGF for 3 days, and was observed using either carbachol or the M1-selective agonist AF102B. The effects of NGF were reflected by larger reductions in membrane-associated APP levels following muscarinic stimulation. These observations imply that M1 muscarinic receptors may act in concert with NGF to boost APP processing, and M1-selective agonists may thus be beneficial for reducing amyloid deposition by NGF-responsive neurons.
Asunto(s)
Precursor de Proteína beta-Amiloide/metabolismo , Carbacol/farmacología , Factores de Crecimiento Nervioso/farmacología , Receptores Muscarínicos/fisiología , Tiofenos , Animales , Diferenciación Celular/efectos de los fármacos , Membrana Celular/metabolismo , Relación Dosis-Respuesta a Droga , Cinética , Células PC12 , Parasimpaticomiméticos/farmacología , Quinuclidinas/farmacología , Ratas , Receptores Muscarínicos/efectos de los fármacos , Proteínas Recombinantes/efectos de los fármacos , Proteínas Recombinantes/metabolismo , Acetato de Tetradecanoilforbol/farmacología , Factores de Tiempo , TransfecciónRESUMEN
This study was designed to evaluate the prophylactic efficacy of transdermally administered physostigmine (PHY) against soman exposure using guinea-pigs. Transdermal PHY pad (3 cm2 kg-1; 60 micrograms cm-2), containing a vehicle based on propionic acid, was applied onto the dorsal back of the animals, 24 h before exposure to the organophosphate. At the time of exposure, PHY concentrations in brain and plasma were ca. 3.6 ng g-1 and 4.1 ng ml-1, respectively. Brain and whole blood cholinesterase (ChE) activity was inhibited to 70% and 47% of the original activity, respectively. Transdermal PHY by itself protected up to 70% of the animals exposed to 1.5 LD50 of soman (100% mortality was recorded in the control group). Combining transdermal PHY with Scopoderm provided full protection against 1.5 LD50 of soman (protection of 70% against 3 LD50). When the prophylactic treatment was combined with post-exposure therapy (atropine, 10 mg kg-1; toxogonin, 10 mg kg-1) 1 min after 5 LD50 of soman, protection of 90% of the animals was achieved.
Asunto(s)
Inhibidores de la Colinesterasa/administración & dosificación , Antagonistas Muscarínicos/administración & dosificación , Fisostigmina/administración & dosificación , Escopolamina/administración & dosificación , Soman/envenenamiento , Administración Cutánea , Animales , Química Encefálica , Inhibidores de la Colinesterasa/farmacología , Colinesterasas/sangre , Femenino , Cobayas , Bombas de Infusión Implantables , Masculino , Antagonistas Muscarínicos/farmacología , Fisostigmina/análisis , Fisostigmina/farmacología , Intoxicación/prevención & control , Escopolamina/farmacología , Soman/administración & dosificaciónRESUMEN
Secretion of amyloid precursor protein (APP) by cultured cells is coupled to several receptors, including m1 muscarinic (m1AChR), and is associated with decreased production of beta A4 amyloid. Secreted and cell-associated APP levels were measured in m1AChR-transfected PC12 cells stimulated with the non-selective agonist carbachol or the M1-selective agonist, AF102B. Secreted APP levels following stimulation with AF102B (5-60 min) were about half compared with carbachol. Yet, following 24 h stimulation with carbachol or AF102B, cell-associated APP levels were similarly decreased. This may be associated with a smaller reduction in APP secretion following 24 h stimulation with AF102B as compared with carbachol. AF102B may therefore have an advantage over non-selective muscarinic ligands for sustained decrease of cell-associated APP.
Asunto(s)
Precursor de Proteína beta-Amiloide/biosíntesis , Parasimpatolíticos/farmacología , Quinuclidinas/farmacología , Receptores Muscarínicos/metabolismo , Tiofenos , Precursor de Proteína beta-Amiloide/aislamiento & purificación , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Carbacol/farmacología , Cinética , Células PC12 , Receptores Muscarínicos/biosíntesis , Receptores Muscarínicos/efectos de los fármacos , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/efectos de los fármacos , Proteínas Recombinantes/metabolismo , TransfecciónRESUMEN
Physostigmine has been reported to improve the memory function of some patients with Alzheimer's Disease (AD). However, the drug has a short half-life and a narrow therapeutic window. To overcome these impediments, we developed a continuous transdermal delivery system and tested it for 2 weeks in 12 AD inpatients, using a single-blind design. No major adverse effects were recorded in any of the patients. Physostigmine plasma concentrations were relatively stable (0.56 +/- 0.10 ng/ml) and correlated well with blood acetylcholinesterase inhibition. Six of the 12 patients reported improved vigilance and concentration, and also had higher scores in all four neuropsychological tests employed (Mini Mental State examination, Short Mental Test [SMT], Wechsler's Memory Scale [WMS], and Buschke's Selective Reminding Test). The performance of two additional patients improved in only two tests (SMT and WMS). Transdermal delivery of physostigmine appears to be safe and may be useful for the treatment of a subset of AD patients.