RESUMO
Multielectrodes have been used with great success to simultaneously record the activity of neuronal populations in awake, behaving animals. In particular, there is great promise in the use of this technique to allow the control of neuroprosthetic devices by human patients. However, it is crucial to fully characterize the tissue response to the chronic implants in animal models ahead of the initiation of human clinical trials. Here we evaluated the effects of unilateral multielectrode implants on the motor cortex of rats weekly recorded for 1-6 months using several histological methods to assess metabolic markers, inflammatory response, immediate-early gene (IEG) expression, cytoskeletal integrity and apoptotic profiles. We also investigated the correlations between each of these features and firing rates, to estimate the impact of post-implant time on neuronal recordings. Overall, limited neuronal loss and glial activation were observed on the implanted sites. Reactivity to enzymatic metabolic markers and IEG expression were not significantly different between implanted and non-implanted hemispheres. Multielectrode recordings remained viable for up to 6 months after implantation, and firing rates correlated well to the histochemical and immunohistochemical markers. Altogether, our results indicate that chronic tungsten multielectrode implants do not substantially alter the histological and functional integrity of target sites in the cerebral cortex.
Assuntos
Eletrofisiologia/métodos , Córtex Motor/fisiologia , Animais , Citoesqueleto/metabolismo , Genes Precoces/genética , Genes Precoces/fisiologia , Inflamação/metabolismo , Masculino , Córtex Motor/metabolismo , Ratos , Ratos WistarRESUMO
Episodic and spatial memories engage the hippocampus during acquisition but migrate to the cerebral cortex over time. We have recently proposed that the interplay between slow-wave (SWS) and rapid eye movement (REM) sleep propagates recent synaptic changes from the hippocampus to the cortex. To test this theory, we jointly assessed extracellular neuronal activity, local field potentials (LFP), and expression levels of plasticity-related immediate-early genes (IEG) arc and zif-268 in rats exposed to novel spatio-tactile experience. Post-experience firing rate increases were strongest in SWS and lasted much longer in the cortex (hours) than in the hippocampus (minutes). During REM sleep, firing rates showed strong temporal dependence across brain areas: cortical activation during experience predicted hippocampal activity in the first post-experience hour, while hippocampal activation during experience predicted cortical activity in the third post-experience hour. Four hours after experience, IEG expression was specifically upregulated during REM sleep in the cortex, but not in the hippocampus. Arc gene expression in the cortex was proportional to LFP amplitude in the spindle-range (10-14 Hz) but not to firing rates, as expected from signals more related to dendritic input than to somatic output. The results indicate that hippocampo-cortical activation during waking is followed by multiple waves of cortical plasticity as full sleep cycles recur. The absence of equivalent changes in the hippocampus may explain its mnemonic disengagement over time.
RESUMO
OBJECTIVE: To determine the clinical manifestations associated with resistant M. tuberculosis infection and the antimicrobial resistance in isolates from Mexican patients. STUDY DESIGN: Epidemiological surveillance. PATIENTS: Tuberculosis confirmed cases. METHODS: Primary resistance: no history of treatment prior to diagnosis. The following critical concentrations (micrograms/mL) were used for susceptibility: isoniazid 0.2 and 1; rifampin 1 and 5; ethambutol 5 and 10; streptomycin 2 and 10; ethionamide 5; kanamycin 6; and para-aminosalicylic acid (PAS) 2 and 10. RESULTS: Eighty-four patients with a mean age of 44.7 years were included; 54 men (64%) and 30 women (36%); most patients were from the Mexico City metropolitan area. In 34 patients there was clinical information available, 26 presented fever and weight loss and 8 respiratory symptoms. Fifty-nine patients (70%) were infected by pan-susceptible M. tuberculosis, and 25 (30%) by a resistant isolate; 17 (68%) of them were resistant to at least two drugs, 16 (64%) to isoniazid and rifampin. The proportion of resistance was: isoniazid 24%, rifampin 19%, streptomycin 12%, ethambutol 10%, PAS 9%, etionamide 7%, and kanamycin 6%. Of 47 patients without previous treatment, eight had a resistant microorganism (17%): 9% resistant to isoniazid, 6% to rifampin, 2% to streptomycin, 6% to PAS and 6% multiresistant. Of 37 patients with history of previous treatment for tuberculosis, 17 (46%) had a resistant isolate; 44% were resistant to isoniazid, 35% to rifampin, 24% to streptomycin, 19% to ethambutol, 12% to PAS and 35% multiresistant. Of the 84 patients, four were physicians infected by a resistant isolate, and seven HIV-infected patients, one with a multiresistant isolate, and another with isoniazid resistance. CONCLUSIONS: Antimicrobial resistance among M. tuberculosis is alarmingly high in Mexico City; these results emphasize the importance of case detection and early isolation of patients.
Assuntos
Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Comorbidade , Resistência Microbiana a Medicamentos , Resistência a Múltiplos Medicamentos , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Vigilância da População , Estudos Retrospectivos , Fatores de Risco , Tuberculose/epidemiologia , População UrbanaRESUMO
In 1985, Blau reported a family with 11 members in four generations affected by granulomatous arthritis, iritis, skin rash, and periarticular synovial cysts. We report a second family with these abnormalities, thereby confirming this syndrome as a distinct familial entity with transmission compatible with autosomal dominant inheritance. Affected members in our family included a mother and two daughters. Disease onset was at 10 months to 8 years of age. Each had uveitis, symmetric polyarthritis, and synovial cysts overlying the ankle and wrist joints. In addition, both daughters had an intermittent generalized erythematous papular rash that on biopsy revealed noncaseating granulomatous infiltration. All three patients improved during alternate-day steroid therapy. Recognition of this disorder as distinct from other, more common causes of arthritis is important because of the apparent autosomal dominant transmission and because of the excellent responses to low-dose steroid therapy.