RESUMO
In this work, we demonstrate a single frequency, high power fiber-laser system, operating at 1550 nm, generating controllable rectangular-shape µs pulses. In order to control the amplified spontaneous emission content, and overcome the undesirable pulse steepening during the amplification, a new method with two seed sources operating at 1550 nm and 1560 nm are used in this system. The output power is about 35 W in CW mode, and the peak power is around 32 W in the pulsed mode. The repetition rate of the system is tunable between 50 Hz to 10 kHz, and the pulse duration is adjustable from 10 µs to 100 µs, with all on the fly electronically configurable design. The system demonstrates excellent long and short time stability, as well as spectral and spatial beam quality.
RESUMO
Hepatocellular Carcinoma (HCC) is one of the most frequent cancers worldwide, however, prognosis remains poor following its discovery. We investigate the Thioredoxin superfamily of proteins as diagnostic markers for HCC. Furthermore, we delineate possible roles of the endoplasmic reticulum member of the superfamily, ERdj5, in carcinogenesis. Using antibodies against Thioredoxin 1, Thioredoxin Reductase 1 and ERdj5, we performed immunohistochemistry on paraffin embedded liver biopsy sections from HCC patients. All three redox proteins exhibited elevated expression levels in tumor tissue compared to internal control, with ERdj5 showing a remarkable 3-fold increase. In vitro cell viability experiments using Hepatocellular Carcinoma HuH7 cells treated with ERdj5 small interfering RNA showed that ERdj5 knockdown cells exhibited less resistance to Doxorubicin (chemotherapy drug), but more resistance to Tunicamycin (Endoplasmic Stress inducer), compared to control cells. In conclusion, we introduce members of the Thioredoxin superfamily as possible immunohistochemical markers in the diagnostics of hepatocellular carcinoma and indicate a potential defensive role for ERdj5 in chemotherapeutic drug resistance.
Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Tiorredoxinas/biossíntese , Linhagem Celular , Linhagem Celular Tumoral , DNA Complementar/biossíntese , DNA Complementar/genética , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Retículo Endoplasmático/fisiologia , Gliceraldeído-3-Fosfato Desidrogenases/genética , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Proteínas de Choque Térmico HSP40 , Humanos , Imuno-Histoquímica , Chaperonas Moleculares/imunologia , Inclusão em Parafina , Projetos Piloto , RNA/biossíntese , RNA/isolamento & purificação , RNA Interferente Pequeno/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estresse Fisiológico/induzido quimicamente , Estresse Fisiológico/metabolismo , Tunicamicina/farmacologiaRESUMO
Recent studies have demonstrated the presence of many different neurotrophic factors in the developing and adult kidney. Due to its production of this mixture of neurotrophic factors, we wanted to investigate whether fetal kidney tissue could be beneficial for neuritic fiber growth and/or cell survival in intracranial transplants of fetal ventral mesencephalic tissue (VM). A retrograde lesion of nigral dopaminergic neurons was performed in adult Fischer 344 male rats by injecting 6-hydroxydopamine into the medial forebrain. The animals were monitored for spontaneous locomotor activity in addition to apomorphine-induced rotations once a week. Four weeks following the lesion, animals were anesthetized and embryonic day 14 VM tissue from rat fetuses was implanted stereotaxically into the dorsal striatum. One group of animals received a cograft of kidney tissue from the same embryos in the same needle track. The animals were then monitored behaviorally for an additional 4 months. There was a significant improvement in both spontaneous locomotor activity (distance traveled) and apomorphine-induced rotations with both single VM grafts and VM-kidney cografts, with the VM-kidney double grafts enhancing the motor behaviors to a significantly greater degree. Tyrosine hydroxylase (TH) immunohistochemistry and image analysis revealed a significantly denser innervation of the host striatum from the VM-kidney cografts than from the single VM grafts. TH-positive neurons were also significantly larger in the cografts compared to the single VM grafts. In addition to the dense TH-immunoreactive innervation, the kidney portion of cografts contained a rich cholinergic innervation, as evidenced from antibodies against choline acetyltransferase (ChAT). The striatal cholinergic cell bodies surrounding the VM-kidney cografts were enlarged and had a slightly higher staining density for ChAT. Taken together, these data support the hypothesis that neurotrophic factors secreted from fetal kidney grafts stimulated both TH-positive neurons in the VM cografts and cholinergic neurons in the host striatum. Thus, these factors may be combined for treatment of degenerative diseases involving both dopaminergic and cholinergic neurons.
Assuntos
Transplante de Tecido Encefálico/fisiologia , Corpo Estriado/lesões , Corpo Estriado/cirurgia , Transplante de Tecido Fetal/fisiologia , Transplante de Rim/fisiologia , Animais , Comportamento Animal , Transplante de Tecido Encefálico/patologia , Sobrevivência Celular , Colina O-Acetiltransferase/metabolismo , Corpo Estriado/patologia , Transplante de Tecido Fetal/patologia , Transplante de Rim/patologia , Masculino , Atividade Motora , Fibras Nervosas/patologia , Fibras Nervosas/fisiologia , Fatores de Crescimento Neural/fisiologia , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/fisiopatologia , Doenças Neurodegenerativas/cirurgia , Oxidopamina/toxicidade , Ratos , Ratos Endogâmicos F344 , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
In 54 patients, transvaginal sacrospinous ligament fixation procedures were reviewed retrospectively. The mean operation time was 15 (12-45) min. The mean blood loss was 126 (110-175) cm3. The only intraoperative complication was a rectal laceration that was repaired primarily. The mean duration of follow-up was 28 (4-54) months. There were only 2 recurrent vaginal vault prolapses. There were 3 cases of cystocele (5.5%), 1 case of rectocele (1.8%), 5 cases of enterocele (9.2%), 3 cases of stress incontinence (5.5%), and 5 cases of dysparonia (9.2%). Sacrospinous ligament fixation can be used as an alternative treatment to vaginal hysterectomy in aged women with medical problems and young women suffering from genital descent with infertility. The procedure has the advantage of avoiding laparatomy, facilitating other vaginal repairs needed during the same operation, preserving vaginal function and shortening the time necessary for anesthesia and surgery.
Assuntos
Ligamentos , Sacro , Prolapso Uterino/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Complicações Pós-Operatórias , Resultado do Tratamento , Prolapso Uterino/complicaçõesRESUMO
Dopamine (DA) release and metabolism within the substantia nigra (SN) were studied in normal rats, rats with unilateral 6-hydroxydopamine (6-OHDA) lesions, and 6-OHDA-lesioned rats treated with glial cells line-derived neurotrophic factor (GDNF). Animals with > 99% DA depletions, as determined by apomorphine-induced circling behavior, also showed significant deficits in several measures of spontaneous motor activity. In vivo microdialysis recordings in the SN were carried out in normal and unilaterally 6-OHDA-lesioned rats. Basal levels of DNA were detectable only in the dialysates of normal animals, and basal levels of t he primary DA metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid were found to be significantly reduced in the SN of 6-OHDA-lesioned animals. In the presence of d-amphetamine, either alone or in combination with potassium, significant reductions in DA release were observed in the SN of 6-OHDA-lesioned animals compared to normal animals. Potassium-evoked DA release alone was not significantly different between the groups. A single intranigral administration of GDNF into 6-OHDA-lesioned animals elicited a significant reduction in apomorphine-induced rotation behavior and a significant increase in spontaneous motor activities. These behavioral changes were apparent at 1 week and persisted through 4 weeks following treatment. In vivo microdialysis showed that, although DA metabolism was altered 1 week following GDNF treatment, DA release was not significantly affected until 4 weeks following treatment.
Assuntos
Dendritos/metabolismo , Dopamina/metabolismo , Fatores de Crescimento Neural , Proteínas do Tecido Nervoso/farmacologia , Fármacos Neuroprotetores/farmacologia , Oxidopamina/farmacologia , Substância Negra/metabolismo , Animais , Apomorfina/farmacologia , Comportamento Animal/efeitos dos fármacos , Agonistas de Dopamina/farmacologia , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Masculino , Microdiálise , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344 , Valores de Referência , Comportamento Estereotipado/efeitos dos fármacos , Estimulação Química , Substância Negra/efeitos dos fármacos , Substância Negra/patologiaRESUMO
One approach to replace lost dopaminergic neurons in Parkinson's disease is to transplant fetal mesencephalic tissue into the striatum. In an attempt to expand the developmental window useful for grafting of mesencephalic tissue and increase the fiber outgrowth from grafted dopaminergic neurons, we have pretreated fetal mesencephalic tissue with the dopaminotrophic factor glial cell line-derived neurotrophic factor (GDNF). Mesencephalic tissue pieces from embryonic day 18-19 Fischer 344 rats were preincubated for 20 min with GDNF (1 microg/microl) or vehicle. Two tissue pieces were then transplanted into the striatum of rats that had been unilaterally lesioned by medial forebrain bundle injections of 6-hydroxydopamine. The animals were tested for apomorphine-induced rotations prior to intracranial grafting. Host rats received intrastriatal injections of 10 microg GDNF or control solution at 10 days and 4 weeks postgrafting. The animals were tested in the rotometer twice monthly following transplantation. Despite the fact that these transplants were from a suboptimal donor stage, the rotations were significantly decreased in both transplanted groups. Immunohistochemical evaluation of the host brains revealed that the overall size of transplanted mesencephalic tissue was significantly increased in the GDNF-treated animals, and that the average size of transplanted tyrosine hydroxylase (TH)-positive neurons was also increased. Furthermore, we found that the innervation density of surrounding host striatal tissue was significantly increased in the GDNF-treated group, as compared with controls. Taken together, these results suggest that treatment of intrastriatal ventral mesencephalon grafts with GDNF can optimize the conditions for intracranial grafting and thus improve the chances for functional recovery following the intrastriatal grafting procedure.