Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
J Neurosurg ; 129(6): 1550-1561, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29451447

RESUMO

OBJECTIVECurrently, there is no treatment that slows or halts the progression of Parkinson's disease. Delivery of various neurotrophic factors to restore dopaminergic function has become a focus of study in an effort to fill this unmet need for patients with Parkinson's disease. Schwann cells provide a readily available source of such factors. This study presents a 12-month evaluation of safety and feasibility, as well as the clinical response, of implanting autologous peripheral nerve grafts into the substantia nigra of patients with Parkinson's disease at the time of deep brain stimulation (DBS) surgery.METHODSStandard DBS surgery targeting the subthalamic nucleus was performed in 8 study participants. After DBS lead implantation, a section of the sural nerve containing Schwann cells was harvested and unilaterally grafted to the substantia nigra. Adverse events were continually monitored. Baseline clinical data were obtained during standard preoperative evaluations. Clinical outcome data were obtained with postoperative clinical evaluations, neuropsychological testing, and MRI at 1 year after surgery.RESULTSAll 8 participants were implanted with DBS systems and grafts. Adverse event profiles were comparable to those of standard DBS surgery with the exception of 1 superficial infection at the sural nerve harvest site. Three participants also reported numbness in the distribution of the sural nerve distal to the harvest site. Motor scores on Unified Parkinson's Disease Rating Scale (UPDRS) part III while the participant was off therapy at 12 months improved from baseline (mean ± SD 25.1 ± 15.9 points at 12 months vs 32.5 ± 9.7 points at baseline). An analysis of the lateralized UPDRS scores also showed a greater overall reduction in scores on the side contralateral to the graft.CONCLUSIONSPeripheral nerve graft delivery to the substantia nigra at the time of DBS surgery is feasible and safe based on the results of this initial pilot study. Clinical outcome data from this phase I trial suggests that grafting may have some clinical benefit and certainly warrants further study to determine if this is an efficacious and neurorestorative therapy.Clinical trial registration no.: NCT01833364 (clinicaltrials.gov).


Assuntos
Estimulação Encefálica Profunda , Transferência de Nervo/métodos , Doença de Parkinson/cirurgia , Nervos Periféricos/transplante , Substância Negra/cirurgia , Idoso , Eletrodos Implantados , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transferência de Nervo/efeitos adversos , Testes Neuropsicológicos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/psicologia , Projetos Piloto , Substância Negra/diagnóstico por imagem , Resultado do Tratamento
3.
J Neurosurg ; 126(4): 1140-1147, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27153166

RESUMO

OBJECTIVE One avenue of intense efforts to treat Parkinson's disease (PD) involves the delivery of neurotrophic factors to restore dopaminergic cell function. A source of neurotrophic factors that could be used is the Schwann cell from the peripheral nervous system. The authors have begun an open-label safety study to examine the safety and feasibility of implanting an autologous peripheral nerve graft into the substantia nigra of PD patients undergoing deep brain stimulation (DBS) surgery. METHODS Multistage DBS surgery targeting the subthalamic nucleus was performed using standard procedures in 8 study participants. After the DBS leads were implanted, a section of sural nerve containing Schwann cells was excised and unilaterally delivered into the area of the substantia nigra. Adverse events were continuously monitored. RESULTS Eight of 8 participants were implanted with DBS systems and grafts. Adverse event profiles were comparable to those of standard DBS surgery. Postoperative MR images did not reveal edema, hemorrhage, or significant signal changes in the graft target region. Three participants reported a patch of numbness on the outside of the foot below the sural nerve harvest site. CONCLUSIONS Based on the safety outcome of the procedure, targeted peripheral nerve graft delivery to the substantia nigra at the time of DBS surgery is feasible and may provide a means to deliver neurorestorative therapy. Clinical trial registration no.: NCT01833364 ( clinicaltrials.gov ).


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson/terapia , Nervos Periféricos/transplante , Substância Negra/cirurgia , Estimulação Encefálica Profunda/métodos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Substância Negra/diagnóstico por imagem , Núcleo Subtalâmico/diagnóstico por imagem , Núcleo Subtalâmico/cirurgia , Resultado do Tratamento
4.
J Neurosurg ; 106(4): 614-20, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17432712

RESUMO

OBJECT: Glial cell line-derived neurotrophic factor (GDNF) infused unilaterally into the putamen for 6 months has been previously shown to improve significantly motor functions and quality of life measures in 10 patients with Parkinson disease (PD) in a Phase I trial. In the present study the authors report the safety and efficacy of continuous treatment for a minimum of 1 year. After the trial was halted by the drug sponsor, the patients were monitored for an additional 1 year during which the effects of drug withdrawal were evaluated. METHODS: During the extended study period, patients received a 30-microg/day unilateral intraputamenal infusion of GDNF at a basal infusion rate supplemented with pulsed boluses every 6 hours at a convection-enhanced delivery rate to increase tissue penetration of the protein. When the study was stopped, the delivery system was reprogrammed to deliver sterile saline at the basal infusion rate of 2 microl/hour. The Unified Parkinson's Disease Rating Scale (UPDRS) total scores after 1 year of therapy were improved by 42 and 38% in the off- and on-medication states; the motor UPDRS scores were also improved 45 and 39%, respectively. Benefits from treatment were lost by 9 to 12 months after the cessation of GDNF infusion. The UPDRS scores returned to their baseline and the patients required higher levels of conventional antiparkinsonian drugs to treat symptoms. After 11 months of treatment, the delivery system had to be removed in one patient because of risk of infection. Seven patients developed antibodies to GDNF but without evident clinical sequelae. There was no evidence for GDNF-induced cerebellar toxicity, as evaluated by magnetic resonance imaging and clinical testing. CONCLUSIONS: The unilateral administration of GDNF results in significant, sustained bilateral benefits in patients with PD. These improvements are lost within 9 months of drug withdrawal. Safety concerns with GDNF therapy can be closely monitored and managed.


Assuntos
Antiparkinsonianos/administração & dosagem , Fator Neurotrófico Derivado de Linhagem de Célula Glial/administração & dosagem , Atividade Motora/fisiologia , Doença de Parkinson/tratamento farmacológico , Suspensão de Tratamento , Idoso , Esquema de Medicação , Feminino , Seguimentos , Humanos , Bombas de Infusão Implantáveis , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Putamen , Resultado do Tratamento
5.
Neurosurg Focus ; 20(5): E1, 2006 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-16711657

RESUMO

OBJECT: Glial cell line-derived neurotrophic factor (GDNF) infused unilaterally into the putamen for 6 months was previously shown to improve motor functions and quality of life measures significantly in 10 patients with Parkinson disease (PD) in a Phase I trial. In this study the authors report the safety and efficacy of continuous treatment for 1 year or more. After the trial was halted by the sponsor, the patients were monitored for an additional year to evaluate the effects of drug withdrawal. METHODS: During the extended study, patients received unilateral intraputaminal infusion of 30 mg/day GDNF at a basal infusion rate supplemented with pulsed boluses every 6 hours at a convection-enhanced delivery rate to increase tissue penetration of the protein. When the study was stopped, the delivery system was reprogrammed to deliver sterile saline at the basal infusion rate of 2 ml/hour. The Unified PD Rating Scale (UPDRS) total scores after 1 year of therapy were improved by 42 and 38%, respectively, in the "off" and "on" states. Motor UPDRS scores were also improved: 45 and 39% in the off and on conditions, respectively. Benefits from treatment were lost by 9 to 12 months after GDNF infusion was halted. At that time, the patients had returned to their baseline UPDRS scores and required higher levels of conventional antiparkinsonian drugs to treat symptoms. After 11 months of treatment, the delivery system had to be removed in one patient because of the risk of infection. In seven patients antibodies to GDNF developed, with no evidence of clinical sequelae. There was also no evidence of GDNF-induced cerebellar toxicity, as evaluated using magnetic resonance imaging analysis and clinical testing. CONCLUSIONS: Unilateral administration of GDNF results in significant, sustained bilateral benefits. These improvements are lost within 9 months after drug withdrawal. Safety concerns with GDNF therapy can be closely monitored and managed.


Assuntos
Fator Neurotrófico Derivado de Linhagem de Célula Glial/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Putamen/efeitos dos fármacos , Idoso , Antiparkinsonianos/uso terapêutico , Ensaios Clínicos Fase I como Assunto , Esquema de Medicação , Feminino , Fator Neurotrófico Derivado de Linhagem de Célula Glial/efeitos adversos , Fator Neurotrófico Derivado de Linhagem de Célula Glial/uso terapêutico , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Movimento/efeitos dos fármacos , Doença de Parkinson/fisiopatologia , Índice de Gravidade de Doença , Resultado do Tratamento
6.
In Vitro Cell Dev Biol Anim ; 41(3-4): 71-6, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16029075

RESUMO

Selected morphological and physiological properties of the corpus allatum (CA)-corpus cardiacum (CC) complex from the two-spotted stinkbug, Perillus bioculatus (Hemiptera: Pentatomidae), were studied. The CAs play an important role in insect physiology because of their production of the juvenile hormones (JHs), i.e., key hormones involved in development and reproduction. We found that the P. bioculatus CA-CC complex is present in two distinct morphological forms, the more frequently observed complex containing one "fused" CA between two CCs and the more rarely observed complex having one CA laterally attached to each CC. These complexes were tested for their ability to synthesize JH-like compounds. We found that the primary lipophilic compound synthesized by the CA-CCs migrated differently from JH III (a JH found in numerous insect species) when subjected to thin-layer chromatography. Furthermore, the synthesis of this compound is stimulated by 2E,6E-farnesol, a known precursor for JH III. These data indicate that the P. bioculatus CA- CC product has chemical properties similar to that of other (as of yet unidentified) hemipteran JHs. In addition, we found that the synthesis of this product is sensitive to pH and buffer type; minimally or not affected by the absence of the CC; expressed at similar levels in days 5-30 postemergent adults; and inhibited or decreased in adults reared under low temperature-short day conditions.


Assuntos
Corpora Allata/citologia , Hemípteros/citologia , Sistemas Neurossecretores/citologia , Animais , Corpora Allata/efeitos dos fármacos , Corpora Allata/fisiologia , Farneseno Álcool/farmacologia , Feminino , Hemípteros/fisiologia , Hormônios Juvenis/fisiologia , Masculino , Neuropeptídeos/fisiologia , Sistemas Neurossecretores/efeitos dos fármacos , Sistemas Neurossecretores/fisiologia
7.
Curr Microbiol ; 48(1): 1-9, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15018095

RESUMO

The active-toxin form of CrylAc (65 kDa) or Cry2Ab was fed to a non-susceptible insect, Lygus hesperus, in an artificial diet. Biochemical and immunocytochemical methods were used to determine the distribution of ingested toxin. The toxins did not elicit a feeding deterrent response. CrylAc and Cry2Ab were ingested; small amounts were absorbed into the hemolymph as holoproteins, but most was excreted. SDS-PAGE analysis of CrylAc and Cry2Ab incubations with salivary gland homogenate showed a small decrease in the molecular weight of the active toxins. Proteolytic processing of the toxins also occurred in vivo, within the digestive system of L. hesperus. Excreted CrylAc and Cry2Ab retained activity toward lepidopteran larvae. Immunocytochemical in vivo localization studies showed negligible association of CrylAc with L. hesperus tissues. In contrast, strong extracellular association of Cry2Ab was observed with L. hesperus midgut brush border microvilli and basement membrane, as well as with cellular outlines within the hemolymph and fat body.


Assuntos
Bacillus thuringiensis/metabolismo , Proteínas de Bactérias/farmacocinética , Toxinas Bacterianas , Endotoxinas/farmacocinética , Lepidópteros/metabolismo , Animais , Toxinas de Bacillus thuringiensis , Western Blotting , Sistema Digestório/efeitos dos fármacos , Sistema Digestório/metabolismo , Eletroforese em Gel de Poliacrilamida , Feminino , Hemolinfa/metabolismo , Proteínas Hemolisinas , Imuno-Histoquímica , Lepidópteros/crescimento & desenvolvimento , Microscopia de Fluorescência , Controle Biológico de Vetores , Distribuição Tecidual
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...