RESUMEN
We sequenced a diabetic Rattus norvegicus Wistar strain mitochondrial genome for the first time (GenBank Accession No. KM114608). Its mitogenome was 16,311 bp and coding 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes. This mitogenome sequence will provide definite genetic information for diabetes disease.
Asunto(s)
Diabetes Mellitus/genética , Genoma Mitocondrial , Animales , Composición de Base/genética , Emparejamiento Base/genética , Secuencia de Bases , ADN Mitocondrial/genética , Modelos Animales de Enfermedad , Orden Génico , Masculino , Polimorfismo de Nucleótido Simple/genética , Ratas WistarRESUMEN
In the present work we undertook the complete mitochondrial genome sequencing of an important insulin resistance model inbred rat strain for the first time. The total length of the mitogenome was 16,308 bp. It harbored 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 non-coding control region (D-loop region). The mutation events were also reported.
Asunto(s)
Genoma Mitocondrial , Resistencia a la Insulina/genética , Mutación/genética , Animales , Secuencia de Bases , Modelos Animales de Enfermedad , Genes Mitocondriales , Ratones Endogámicos C57BL , ARN de Transferencia/genéticaRESUMEN
BACKGROUND: Human pancreatic islet transplantation is a prospective curative treatment for diabetes. However, the lack of donor pancreases greatly limits this approach. One approach to overcome the limited supply of donor pancreases is to generate functional islets from human embryonic stem cells (hESCs), a cell line with unlimited proliferative capacity, through rapid directed differentiation. This study investigated whether pancreatic insulin-producing cells (IPCs) differentiated from hESCs could correct hyperglycemia in severe combined immunodeficient (SCID)/non-obese diabetic (NOD) mice, an animal model of diabetes. METHODS: We generated pancreatic IPCs from two hESC lines, YT1 and YT2, using an optimized four-stage differentiation protocol in a chemically defined culture system. Then, about 5-7 × 10(6) differentiated cells were transplanted into the epididymal fat pad of SCID/NOD mice (n = 20). The control group were transplanted with undifferentiated hESCs (n = 6). Graft survival and function were assessed using immunohistochemistry, and measuring serum human C-peptide and blood glucose levels. RESULTS: The pancreatic IPCs were generated by the four-stage differentiation protocol using hESCs. About 17.1% of differentiated cells expressed insulin, as determined by flow cytometry. These cells secreted insulin/C-peptide following glucose stimulation, similarly to adult human islets. Most of these IPCs co-expressed mature ß cell-specific markers, including human C-peptide, GLUT2, PDX1, insulin, and glucagon. After implantation into the epididymal fat pad of SCID/NOD mice, the hESC-derived pancreatic IPCs corrected hyperglycemia for ≥ 8 weeks. None of the animals transplanted with pancreatic IPCs developed tumors during the time. The mean survival of recipients was increased by implanted IPCs as compared to implanted undifferentiated hESCs (P<0.0001). CONCLUSIONS: The results of this study confirmed that human terminally differentiated pancreatic IPCs derived from hESCs can correct hyperglycemia in SCID/NOD mice for ≥8 weeks.
Asunto(s)
Diferenciación Celular , Diabetes Mellitus Experimental/terapia , Células Madre Embrionarias/trasplante , Células Secretoras de Insulina/trasplante , Animales , Glucemia , Péptido C/sangre , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/patología , Modelos Animales de Enfermedad , Humanos , Insulina/metabolismo , Secreción de Insulina , Trasplante de Islotes Pancreáticos , Ratones , Ratones Endogámicos NOD , Páncreas/metabolismo , Páncreas/patologíaRESUMEN
OBJECTIVE: To investigate the clinical manifestations, treatment and prognosis of antiphospholipid syndrome (APS). METHODS: The cases of 72 patients with defined APS admitted from Jan 1990 to Jan 2006 were analyzed retrospectively. RESULTS: 21 patients with primary APS and 51 patients with secondary APS were studied. Vascular thrombosis was present in 43 (59.7%) of the 72 patients in this study. Cardiac abnormalities could be observed in 48 patients (66.6%). Lesions most frequently involved left-sided valves, mitral (35.4%) more commonly affected than aortic (16.7%). Cardiac involvement was significantly related to thrombosis (P = 0.007) and prolonged activated partial thromboplastin time (APTT) (P = 0.026). Valvular involvement was significantly related to brain infarcts (P = 0.008) and thrombosis (P = 0.029). 20 APS patients with cardiac abnormalities and thrombosis received anticoagulation therapy and thrombosis did not happen any more during follow-up. CONCLUSION: Cardiac manifestations of APS are valve abnormalities (valve thickening and vegetations), occlusive arterial disease (atherosclerosis and myocardial infarction), ventricular dysfunction and pulmonary hypertension. Cardiac abnormalities in APS are likely to be related to hypercoagulability.
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Síndrome Antifosfolípido/complicaciones , Enfermedades de las Válvulas Cardíacas/etiología , Tromboembolia/etiología , Adulto , Anciano , Anticuerpos Anticardiolipina/análisis , Síndrome Antifosfolípido/inmunología , Femenino , Estudios de Seguimiento , Humanos , Inhibidor de Coagulación del Lupus/análisis , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
STUDY DESIGN: Thoracic spinal cord transections were performed in adult rats. The animals were divided into two groups, with or without internal fixation of the involved vertebral column. Histologic and immunohistochemical studies were performed to compare the effect of internal fixation of the vertebral column. OBJECTIVES: To find out the aspects and extent of beneficial effects of vertebral column fixation for spinal cord repair. SUMMARY OF BACKGROUND DATA: Vertebral column fixation is a routine procedure in clinical spinal cord surgery. Paradoxically, most, if not all, animal spinal cord experiments seem to have ignored the importance of vertebral column fixation. During trunk movements, the vertebral column flexes to different directions, accompanied by bending of the spinal cord. Following spinal cord lesions, with frequent bending of the cord there will be repeated bleeding, inflammation, and other pathologic processes at the lesion site. Thus, the healing process will be hampered. The severity of the damages that will be brought about by bending of the cord is, to a certain degree, unpredictable. There will be rather big individual variations in injury and repair among the same type of experiments, rendering quantification and conclusion difficult. METHODS: Adult Sprague-Dawley rats were used. The thoracic spinal cord was transected. Strong stainless steel wires were used for internal fixation of the vertebral column. The histology of the horizontal sections of the spinal cord segment, which included the lesion site, was examined at the 14th postoperative day. The volumes of the secondary degeneration and meningeal scar, the gap between the borders of the proximal and distal stumps of the transected spinal cord, the thickness of the meningeal scar, the astrocytic reaction, and the abundance of regenerating nerve fibers at the lesion site were compared between the vertebral column fixed and nonfixed groups. Whenever possible, the results were evaluated quantitatively. RESULTS: In all these aspects, the internally fixed group was consistently far better than the unfixed group. The quantitative analyses were as follows (fixed/unfixed): 1)volume of secondary degeneration: 1.07 +/- 0.20/1.81 +/- 0.43 mm3 (P < 0.01); 2) volume of meningeal scar: 2.38 +/- 0.55/4.34 +/- 1.40 mm3 (P < 0.05); 3) distance between cord stumps: 1.38 +/- 0.34/2.35 +/- 0.79 mm (P < 0.05); 4) the mean thinnest dimension of the meningeal scar: 0.90 +/- 0.43/1.98 +/- 0.85 mm (P < 0.05). CONCLUSION: Vertebral column fixation is a crucial procedure for spinal cord animal experiments.
Asunto(s)
Traumatismos de la Médula Espinal/prevención & control , Médula Espinal/patología , Fusión Vertebral , Traumatismos Vertebrales/cirugía , Columna Vertebral/cirugía , Animales , Astrocitos/metabolismo , Astrocitos/patología , Cicatriz/patología , Modelos Animales de Enfermedad , Proteína Ácida Fibrilar de la Glía/biosíntesis , Inmunohistoquímica , Fijadores Internos , Proteínas de Neurofilamentos/biosíntesis , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Traumatismos de la Médula Espinal/patología , Fusión Vertebral/instrumentación , Traumatismos Vertebrales/patologíaRESUMEN
Primacy and recency effects refer to the better performance or shorter response time on the first and last items than the middle ones of a memory list. In order to investigate its neural basis in auditory short-term memory, event-related fMRI was used to measure brain activities when subject was recalling the first, the last, or the middle items. Recalling the middle item was associated with more extensive activation in the left parietal and visual cortex, basal ganglia, and dorsal cerebellum. Recalling items from different serial positions also resulted in different activation time courses in the bilateral primary auditory cortex, left prefrontal cortex and left premotor cortex. These data indicate that the auditory cortex may serve as a transient storage or the auditory input buffer, which seems to play an important role in the primacy and recency effects.
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Mapeo Encefálico , Corteza Cerebral/fisiología , Imagen por Resonancia Magnética/métodos , Memoria a Corto Plazo/fisiología , Recuerdo Mental/fisiología , Estimulación Acústica , Adulto , Percepción Auditiva/fisiología , Ganglios Basales/fisiología , Cerebelo/fisiología , Corteza Cerebral/anatomía & histología , Femenino , Humanos , Imagen por Resonancia Magnética/instrumentación , Masculino , Distribución Aleatoria , Tiempo de Reacción/fisiología , Aprendizaje Seriado , Aprendizaje Verbal/fisiologíaRESUMEN
Lead is one of the most common neurotoxic metals present in our environment. Chronic developmental lead exposure is known to be associated with cognitive dysfunction in children. Functional and morphological impairment of the rat brain has also been reported in the hippocampus (Hi) following developmental lead exposure. The present study was carried out to further investigate age-related morphological impairments in the rat Hi following developmental lead exposure with three methods: (1) magnetic resonance imaging (MRI); (2) light microscopy (LM); and (3) electron microscopy (EM) techniques. Neonatal Wistar rats were exposed to lead from parturition to weaning via milk of dams drinking a 0.2% lead acetate solution. Age-related morphological alternations were investigated in the Hi of lead-exposed rats at various postnatal ages: postnatal day (PND) 17, 30 and 90. The MRI signal intensities (SIs) in the left, right, superior and inferior hippocampal regions of control and lead-exposed rats were analyzed. Compared with controls, the SIs of the four hippocampal regions of interest were significantly increased in lead-exposed rats at PND 17, 30 and 90. Moreover, the lead-induced impairment of the Hi showed an age-related decline and a specific topographical pattern. The impairment of inferior hippocampal regions was more severe than that of superior regions in lead-exposed rats at PND 17 and 30, while no significant difference of SIs was observed between left and right hippocampal regions in the three age groups, and between superior and inferior regions in the PND 90 lead-exposed rats. The LM observations indicated that the morphological injury of hippocampal neurons in lead-exposed rats was also age-related. The EM observations revealed that the endoplasmic reticular, Golgi complex and mitochondria of hippocampal CA1 and dentate gyrus neurons in lead-exposed rats were damaged. These results demonstrate that lead-induced morphological impairments of the rat Hi follow a specific age- and site-related pattern.