Influência do tamoxifeno associado ao diabete melito na densidade mineral óssea

Considering that osteopenia and osteoporosis are diabetes mellitus complications, and that tamoxifen (TAM) is an anti-estrogenic drug used in breast cancer treatment, this drug may have a beneficial action preventing accentuaded bone loss associated to diabetes. Female Wistar rats (n=60) weighting 180-250g were divided in four groups: Group C, control animals (n=5); Group T, animals treated with TAM (n=5); Group D, diabetic animals (n=5); and Group DT, diabetic animals treated with TAM (n=5). Oestrus cycle was evaluated before the beggining of experimental period to select the animals with regular cycle. This evaluation continued throughout the study period and for all studied groups. Diabetes was induced by a intra perithoneal injection of streptozotocin (STZ) in a concentration of 45 mg/Kg of body weight. Those animals with serum glicose levels 250 mg/dL were considered diabetics. Animals were sacrificed in the periods of 30, 60 and 90 days after diabetes onset. Left femur histomorphometric measurements and serum biochemical analysis (glycemia, alkaline phosphatase, tartaric-resistant acid phosphatase, calcium, phosphorous, magnesium, total proteins, albumin, globulins, urea and creatinine) were done. Histomorphometric results showed a progressive bone loss in Group D animals when compared to those from Group C all over the experimental period, becoming accentuaded in the 90 days period. In relation to Groups T and DT, values approcimated to those obtained for control group were found during the whole period of study. Those data may indicate a bone mass recovery or a diminished bone loss due to diabetes when animals were treated with TAM. During the whole experimental period animals of groups D and DT maintained glycemic levels above 250 mg/dL whereas animals of groups C and T maintained those levels below 150mg/dL. Alkaline phosphatase activity was increased in all study periods for groups D and DT when compared to group C animals over the 90 days period. Tartarate-resistant acid phosphatase activity was showed unaltered in all periods of study and for all groups. Calcium and magnesium results were also unaltered, maintaining reference levels for all groups in all experimental periods. Phosphorous levels were increased in groups D and DT when compared to groups C and T in the 30 days period. However no difference was found in the periods of 60 and 90 days for this test. No difference was found for total proteins levels for groups C, T, D and DT over the study period. Albumin levels were reduced in DT group in the 60 days period and in D and DT groups in the 90 days period. Urea levels were significantly increased in the 30, 60 and 90 days study periods in groups D and DT when compared to groups C and T. Creatinine results showed a significantly increase in the 90 days period for groups D and DT when compared to groups C and T, and maintaining unaltered in the 30 and 60 days periods. These results suggest that the treatment with TAM may reduce bone loss caused by diabetes mellitus

Modelo animal da Doença de Parkinson baseado na expressão de alfa - sinucleína: caracterização comportamental, eletrofisiológica e avaliação dos efei tos da estimulação da medula espinhal

Parkinson disease (PD) is associated with motor symptoms and dopaminergic cell loss in the nigrostriatal pathway. Alpha-synuclein is the major component of the Lewy bodies, the biological hallmarks of disease, and has been associated with familial cases of PD. Recently, the spinal cord stimulation (SCS) showed to be effective to alleviate the Parkinson symptoms in animal models and human patients. In this project, we characterized the motor and electrophysiological effects of alpha-synuclein overexpression in the substantia nigra of rats. We further investigated the effects of spinal electrical stimulation, AMPT and L-dopa administration in this model. Method: Sprague-Dawley rats were injected with empty viral vector or the vector carrying the gene for alpha-synuclein in the substantia nigra, and were tested weekly for 10 weeks in the open field and cylinder tests. A separated group of animals implanted with bilateral electrode arrays in the motor cortex and the striatum were recorded in the open field, during the SCS sessions and the pharmacological experiments. Results: Alpha-synuclein expression resulted in motor asymmetry, observed as the reduction in use of contralateral forepaw in the cylinder test. Animals showed an increase of local field potential activity in beta band three and four weeks after the virus injection, that was not evident after the 5th week. AMPT resulted in a sever parkinsonian state, with reduction in the locomotor activity and significant peak of oscillatory activity in cortex and striatum. SCS was effective to alleviate the motor asymmetry at long term, but did not reduce the corticostriatal low frequency oscillations observed 24 hs after the AMPT administration. These oscillations were attenuated by L-dopa that, even as SCS, was not effective to restore the locomotor activity during the severe dopaminergic depletion period. Discussion: The alpha-synuclein model reproduces the motor impairment and the progressive neurodegenerative process of PD. We demonstrated, by the first time, that this model also presents the increase in low frequency oscillatory activity in the corticostriatal circuit, compatible with parkinsonian condition; and that SCS has a therapeutic effect on motor symptom of this model.