RESUMEN
This study investigated the ability of the immunosuppressant FK506 to reverse nerve allograft rejection in progress. Eighty-four Buffalo rats received posterior tibial nerve grafts from either Lewis or Buffalo donor animals. Allografts were left untreated for either 7, 10, or 14 days before receiving daily subcutaneous FK506 injections (2 mg/kg). Time-matched control animals received either an isograft, an allograft with continuous FK506, or an allograft with no postoperative FK506 therapy. All animals underwent weekly evaluation of nerve function by walking track analysis. Experimental group animals were sacrificed either immediately prior to initiation of FK506 therapy (days 7, 10, or 14), after 2 weeks of immunosuppressive treatment, or 8 weeks postsurgery. Histomorphometric analysis, consisting of measurements of total number of nerve fibers, neural density, and percent of neural debris, demonstrated a statistically significant increase in regeneration in the isograft group relative to the untreated allograft group within 28 days of transplantation. Grafts harvested from animals receiving 2 weeks of FK506 after 7 or 10 days of rejection were histomorphometrically similar to time-matched isografts. By contrast, grafts from animals receiving 2 weeks of FK506 following 14 days without therapy resembled untreated allografts and demonstrated significant histomorphometric differences from isografts at the corresponding time point. Analysis of walking track data confirmed that relative to untreated allografts, functional recovery was hastened in animals receiving an isograft, or allograft treated with FK506. This study demonstrated that when started within 10 days of graft placement, FK506 could reverse nerve allograft rejection in rats evaluated following 2 weeks of treatment.
Asunto(s)
Rechazo de Injerto/tratamiento farmacológico , Inmunosupresores/farmacología , Tacrolimus/farmacología , Nervio Tibial/trasplante , Enfermedad Aguda , Animales , Rechazo de Injerto/inmunología , Rechazo de Injerto/patología , Prueba de Cultivo Mixto de Linfocitos , Masculino , Ratas , Ratas Endogámicas BUF , Ratas Endogámicas Lew , Trasplante HomólogoRESUMEN
The effects of cultured host Schwann cells on axonal regeneration in peripheral nerve allografts were studied. Fischer rats served as recipient animals and Buffalo rats provided nerve allografts. Animals were randomized into 9 groups. Rats receiving tibial nerve isografts were left untreated (group I), or injected with isogeneic Fischer Schwann cells (group II) or placebo suspension (group III). Allografts obtained from Buffalo rats were left untreated (group IV), or received isogeneic Fischer Schwann cells (group V), 2 mg/kg Cyclosporin A and Fischer Schwann cells (group VI), 5 mg/kg Cyclosporin A (group VII), or 5 mg/kg Cyclosporin A with Schwann cells (group VIII). No Schwann cell tumors were identified 4 or 8 weeks postoperatively. Group IX animals, harvested 3 days postoperatively, demonstrated no evidence of injection injury. Schwann cells modestly improved axonal regeneration in both isografts and allografts and may have a clinical role in the treatment of peripheral nerve allografts.
Asunto(s)
Nervios Periféricos/trasplante , Células de Schwann , Animales , Células Cultivadas , Inyecciones , Regeneración Nerviosa , Nervios Periféricos/citología , Ratas , Ratas Endogámicas BUF , Ratas Endogámicas F344 , Células de Schwann/citologíaRESUMEN
OBJECTIVES: To examine the presence or absence of dementia, and the prevalence rates for different dementias, in patients with and without adult onset diabetes (AODM). DESIGN: Chart survey. SETTING: A public long-term care facility in Rochester, New York, chosen to provide an enriched sample with respect to the diseases and demographic variables of interest. PARTICIPANTS: All long-term care residents in the facility aged 50 years or older (n = 476), mean age 74.8 years. Thirty-six (7.6%) had probable Alzheimer's disease (AD), 49 (10.3%) had possible AD, 38 (8.0%) had clinically diagnosed vascular dementia, 84 (17.6%) had unspecified dementias, and 269 (56.5%) were not demented. MEASUREMENTS: Demographic data, dementia and diabetes determined on the basis of extraction of chart data, and hypertension, myocardial infarction, congestive heart failure, and hypercholesterolemia determined on the basis of chart diagnoses. RESULTS: There were 99 residents with AODM in the sample, a prevalence rate of about 21%. The rates of both dementia and AODM were as expected for this age group and setting. Patients with probable or possible AD had the lowest rates of AODM (0 and 6.1%, respectively), and patients with vascular dementia had the highest rates of AODM (47.4%). Age, sex, and race influenced both the risk of having a dementia and the type of dementia. When these variables were adjusted for in multiple logistic regression, however, AODM remained a robust predictive factor because of its significant negative association with AD. Patients with unspecified dementias and no dementia showed rates of AODM (about 20%) that were roughly comparable and intermediate between vascular dementia and AD. CONCLUSIONS: In our study, AD diagnosed clinically and AODM did not co-occur, whereas AODM was associated with vascular dementia diagnosed clinically. Conversely, in non-Alzheimer, nonvascular dementias diagnosed clinically, the rates of AODM were equivalent to those in nondemented patients. These findings are in agreement with some, but not all, previous studies.
Asunto(s)
Demencia/etiología , Diabetes Mellitus Tipo 2/complicaciones , Cuidados a Largo Plazo/estadística & datos numéricos , Distribución por Edad , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Demencia/clasificación , Femenino , Humanos , Modelos Logísticos , Masculino , New York , Valor Predictivo de las Pruebas , Prevalencia , Grupos Raciales , Factores de Riesgo , Distribución por Sexo , Instituciones de Cuidados Especializados de Enfermería/estadística & datos numéricosRESUMEN
Insulin-stimulated glucose uptake is defective in patients with type 2 diabetes. To determine whether transgenic glucose transporter overexpression in muscle can prevent diabetes induced by a high-fat, high-sugar diet, singly (GLUT-1, GLUT-4) and doubly (GLUT-1 and -4) transgenic mice were placed on a high-fat, high-sugar diet or a standard chow diet. On the high-fat, high-sugar diet, wild-type but not transgenic mice developed fasting hyperglycemia and glucose intolerance (peak glucose of 337 +/- 19 vs. 185-209 mg/dl in the same groups on the high-fat, high-sugar diet and 293 +/- 13 vs. 166-194 mg/dl on standard chow). Hyperinsulinemic clamps showed that transporter overexpression elevated insulin-stimulated glucose utilization on standard chow (49 +/- 4 mg. kg-1. min-1 in wild-type vs. 61 +/- 4, 67 +/- 5, and 63 +/- 6 mg. kg-1. min-1 in GLUT-1, GLUT-4, and GLUT-1 and -4 transgenic mice given 20 mU. kg-1. min-1 insulin, and 54 +/- 7, 85 +/- 4, and 98 +/- 11 in wild-type, GLUT-1, and GLUT-4 mice given 60-80 mU. kg-1. min-1 insulin). On the high-fat, high-sugar diet, wild-type and GLUT-1 mice developed marked insulin resistance, but GLUT-4 and GLUT-1 and -4 mice were somewhat protected (glucose utilization during hyperinsulinemic clamp of 28.5 +/- 3.4 vs. 42.4 +/- 5.9, 51.2 +/- 8.1, and 55.9 +/- 4. 9 mg. kg-1. min-1 in wild type, GLUT-1, GLUT-4, GLUT-1 and -4 mice). These data demonstrate that overexpression of GLUT-1 and/or GLUT-4 enhances whole body glucose utilization and prevents the development of fasting hyperglycemia and glucose intolerance induced by a high-fat, high-sugar diet. GLUT-4 overexpression improves the insulin resistance induced by the diet. We conclude that upregulation of glucose transporters in skeletal muscle may be an effective therapeutic approach to the treatment of human type 2 diabetes.