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1.
Anticancer Res ; 41(9): 4271-4276, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475046

RESUMO

BACKGROUND/AIM: The anticancer mechanism of itraconazole remains unsolved; therefore, we studied itraconazole-induced alterations in specialized pro-resolving mediators (SPMs) in cancer cells. MATERIALS AND METHODS: The human cervical squamous carcinoma cell line CaSki was cultured with or without 1 µM itraconazole. Liquid chromatography/mass spectrometry analysis was conducted to identify SPMs that were influenced by itraconazole. Cell growth experiments were conducted using itraconazole and inhibitors targeting the metabolic pathways of candidate SPMs. RESULTS: Resolvin E3, resolvin E2, prostaglandin J2 (PGJ2), delta-12-PGJ2, and maresin 2 were identified as candidate SPMs. The 12/15-lipoxygenase inhibitor, which is involved in the conversion of 18-hydroxy-eicosapentaenoic acid to resolvin E3, attenuated the inhibitory effect of itraconazole. Inhibition of the PGJ2 metabolic pathway did not interfere with itraconazole treatment. CONCLUSION: The metabolic pathway of SPMs, including resolving E3, could be proposed as an anticancer target of itraconazole.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Ácidos Graxos Insaturados/metabolismo , Itraconazol/farmacologia , Inibidores de Lipoxigenase/farmacologia , Neoplasias do Colo do Útero/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Espectrometria de Massas , Redes e Vias Metabólicas/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico
2.
Gynecol Oncol Rep ; 32: 100563, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32300630

RESUMO

A germline pathogenic variant in BRCA2 was secondarily found through genomic sequencing of uterine serous carcinoma. Clinical response to olaparib was observed in recurrent uterine serous carcinoma with a germline BRCA2 mutation. Here, we report, for the first time, a long-term clinical response to olaparib in a patient with uterine serous carcinoma and a germline pathogenic BRCA2 variant.

3.
J Obstet Gynaecol Res ; 45(1): 203-209, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30117238

RESUMO

AIM: To investigate the effects of leuprorelin using a self-administered quality-of-life (QOL) questionnaire in patients with recurrent gynecological cancer. METHODS: Records of patients who received 3.75 mg leuprorelin every 4 weeks for the treatment of recurrent gynecological cancer were retrospectively reviewed. The physical domain of the QOL questionnaire, Care Notebook, was used to assess physical symptoms. Symptom deterioration was defined as a ≥10-point increase in baseline score; otherwise, symptoms were defined as controlled. Radiological and serological responses were evaluated according to the 2011 Gynecological Cancer Intergroup criteria. RESULTS: From 2007 to 2015, 25 patients were administered leuprorelin for the treatment of epithelial ovarian cancer, granulosa cell tumor, endometrial cancer, endometrial stromal sarcoma and clear cell cervical cancer (in 13, 3, 6, 2 and 1 patients, respectively). Twenty patients had received a median of three lines (range 1-12 lines) of chemotherapy. Ten patients had progressive disease during their previous round of chemotherapy. Twenty patients completed the questionnaire every 4 weeks. Following leuprorelin treatment for 8 weeks, the symptom and disease control rates were 65% (13/20) and 44% (11/25), respectively. Two patients, one each with granulosa cell tumor and endometrial cancer, had stable disease at 6 months. Among the 20 patients who completed the QOL questionnaire, symptom control and disease control at 8 weeks showed a significant correlation (P = 0.016). CONCLUSION: Leuprorelin had minimal anticancer activity. The physical domain of the QOL questionnaire could be used to assess effects of hormonal treatment.


Assuntos
Antineoplásicos Hormonais/farmacologia , Neoplasias dos Genitais Femininos/tratamento farmacológico , Leuprolida/farmacologia , Recidiva Local de Neoplasia/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/administração & dosagem , Feminino , Humanos , Leuprolida/administração & dosagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários
4.
Graefes Arch Clin Exp Ophthalmol ; 256(11): 2191-2200, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30171351

RESUMO

PURPOSE: We compared the outcomes of Baerveldt glaucoma implant (BGI) surgery between vitreous cavity and anterior chamber insertion. METHODS: We retrospectively analyzed a total of 105 consecutive eyes that underwent BGI surgery and were followed up for ≥ 12 months. BGI surgery was performed via the anterior chamber (AC group 48 eyes) or the pars plana into the vitreous cavity (VC group 57 eyes). Patients' data were examined at 3, 6, and 12 months, and then every 6 months after surgery. We compared the groups' intraocular pressure (IOP), success ratio, visual acuity, number of glaucoma medications, central corneal endothelial cell density (CCECD), reduction ratio of CCECD, and postoperative complications. RESULTS: The mean preoperative and postoperative IOP values were not significantly different between the two groups. In the Kaplan-Meier survival plots, there was no significant between-group difference in the success rate (p = 0.333). The postoperative mean CCECD decreased significantly faster in the AC group than the VC group at all time points. The cases of postoperative corneal edema were 12.5% in AC group and 1.8% in VC group. The risk of postoperative corneal edema was significantly higher in the AC group (p = 0.0136). Risk factors for the rapid reduction of CCECD were "history of trabeculectomy" (p = 0.00283), "insertion into the anterior chamber" (p = 0.001), and "shorter distance between the tube and corneal endothelium" (p = 0.0137). CONCLUSION: There was no significant between-group difference in postoperative IOP, medications, or success rate. Considering the reduction of corneal endothelial cells, insertion into the vitreous cavity seems safer than insertion into the anterior chamber.


Assuntos
Câmara Anterior/cirurgia , Implantes para Drenagem de Glaucoma , Glaucoma/cirurgia , Implantação de Prótese/métodos , Corpo Vítreo/cirurgia , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Contagem de Células , Endotélio Corneano/citologia , Feminino , Glaucoma/fisiopatologia , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia de Coerência Óptica , Tonometria Ocular , Resultado do Tratamento , Acuidade Visual/fisiologia
5.
Gynecol Oncol Rep ; 24: 57-60, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29682600

RESUMO

Standard chemotherapy for women with advanced or recurrent cervical cancer involves a combination of paclitaxel, platinum, and bevacizumab. However, for patients who experience anaphylaxis in response to paclitaxel or platinum, have permanent peripheral neuropathy, or develop early recurrence or progressive disease during first-line chemotherapy, the development of a non-taxane non-platinum regimen is mandatory. Clinical trials using anti-angiogenic treatment demonstrated favorable outcomes in cases of highly vascularized cervical cancer. Metronomic chemotherapy has been considered an anti-angiogenic treatment, although its use in combination with bevacizumab has not been studied in cervical cancer. We treated four patients with recurrent cervical cancer with 50 mg of oral cyclophosphamide daily and 15 mg/kg of intravenous bevacizumab every 3 weeks (CFA-BEV). One patient experienced disease progression after 4 months, whereas the other three patients continued the regimen until their last follow-up at 13, 14, and 15 months, respectively. One patient suffered from grade 3 neutropenia; however, no grade 2 or higher non-hematological toxicities were observed. These cases demonstrate the use of CFA-BEV with minimal toxicity and expected anti-cancer activity and indicate that this regimen should be considered for second-line chemotherapy in advanced recurrent cervical cancer.

6.
Oncol Lett ; 14(2): 1240-1246, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28789339

RESUMO

Itraconazole, a common anti-fungal agent, has demonstrated potential anticancer activity, including reversing chemoresistance mediated by P-glycoprotein, modulating the signal transduction pathways of Hedgehog, mechanistic target of rapamycin and Wnt/ß-catenin in cancer cells, inhibiting angiogenesis and lymphangiogenesis, and possibly interfering with cancer-stromal cell interactions. Clinical trials have suggested the clinical benefits of itraconazole monotherapy for prostate cancer and basal cell carcinoma, as well as the survival advantage of combination chemotherapy for relapsed non-small cell lung, ovarian, triple negative breast, pancreatic and biliary tract cancer. As drug repurposing is cost-effective and timesaving, a review was conducted of preclinical and clinical data focusing on the anticancer activity of itraconazole, and discusses the future directions for repurposing itraconazole as an anticancer agent.

7.
Anticancer Res ; 37(7): 3521-3526, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28668841

RESUMO

BACKGROUND/AIM: Repurposing itraconazole as an anticancer agent has been evaluated in several studies. The present study investigated whether itraconazole exerts an anticancer effect on cervical cancer cells. MATERIALS AND METHODS: CaSki and HeLa cells were cultured in itraconazole and vehicle after which colony-forming and cell viability assays were performed. Transcription and protein expression were assessed by cDNA microarray analysis and immunoblotting, respectively. RESULTS: Itraconazole suppressed proliferation of CaSki and HeLa cells in a dose- and time-dependent manner. Furthermore, CaSki cells were more significantly affected by itraconazole than HeLa cells. The microarray analysis showed an 8-fold down-regulation in the expression of GLI1, WNT4 and WNT10A among itraconazole-treated CaSki cells. Moreover, the transcription of sterol carrier protein-2 and ATP-binding cassette transporter-1 was unaffected by itraconazole. Immunoblots showed suppression in ß-catenin expression and Akt phosphorylation. CONCLUSION: Itraconazole is a multi-targeting anticancer agent and a promising therapeutic agent for cervical cancer.


Assuntos
Proliferação de Células/efeitos dos fármacos , Proteínas Hedgehog/metabolismo , Itraconazol/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Antineoplásicos/farmacologia , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Transdução de Sinais/efeitos dos fármacos , Neoplasias do Colo do Útero/metabolismo , Proteína Wnt4/metabolismo , Proteína GLI1 em Dedos de Zinco/metabolismo
8.
Anticancer Res ; 37(2): 515-519, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28179296

RESUMO

BACKGROUND: Itraconazole is a common antifungal agent that has demonstrated anticancer activity in preclinical and clinical studies. This study investigated whether itraconazole exerts this effect in endometrial cancer (EC) cells. MATERIALS AND METHODS: Cell viability was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and gene and protein expression were assessed by microarray analysis and immunoblotting, respectively, in five EC cell lines. RESULTS: Itraconazole-suppressed proliferation of AN3-CA, HEC-1A and Ishikawa cells (p<0.05) but not of HEC-50B or SNG-II cells. Itraconazole did not suppress GLI1 or GLI2 transcription but did inhibit the expression of mammalian target of rapamycin (mTOR) signaling components in AN3-CA and HEC-1A cells, while inducing that of microtubule-associated protein 1A/1B-light chain 3-II, a marker of autophagy. ATP-binding cassette transporter A1 gene was down-regulated in Ishikawa, HEC-50B and SNG-II cells. CONCLUSION: Itraconazole treatment suppresses the growth of EC cells by inhibiting AKT/mTOR signalling.


Assuntos
Neoplasias do Endométrio/tratamento farmacológico , Itraconazol/farmacologia , Proteína Oncogênica v-akt/antagonistas & inibidores , Serina-Treonina Quinases TOR/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Proteína Oncogênica v-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
9.
Nippon Ganka Gakkai Zasshi ; 121(2): 138-45, 2017 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-30080004

RESUMO

Purpose: To evaluate the efficacy and safety of the Baerveldt® glaucoma implant (BGI) for eyes with neovascular glaucoma (NVG). Methods: This was a retrospective study. Thirty-five eyes (31 patients) diagnosed with refractory NVG at Toyama University Hospital were enrolled from January 2012 to December 2015. All patients underwent BGI and were followed up for more than 6 months. Results: The mean age of patients was 62.7±13.9 years old. The mean postoperative follow-up periods was 22.0±12.7 months. The mean preoperative IOP was 35.5±9.6 mmHg and the mean postoperative IOP at 6, 12, 24, 36, 48 month were 12.7±5.9, 12.8±3.7, 12.2±3.3, 13.1±3.3, 15.0±1.4 mmHg respectively. Postoperative visual acuity was not significantly improved. Complications were Hoffmann Elbow erosion in 2 patients who needed additional surgery. The success rate at one year was 82.7%. Postoperative intervention was not required. Conclusion: BGI surgery should be considered a useful treatment to lower the IOP for NVG.


Assuntos
Implantes para Drenagem de Glaucoma , Glaucoma Neovascular/fisiopatologia , Glaucoma Neovascular/cirurgia , Idoso , Feminino , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Período Pós-Operatório , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual
10.
Gynecol Oncol Rep ; 16: 11-3, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27331128

RESUMO

•An ovarian clear cell carcinoma patient showed malignant pericardial and pleural effusion.•She subsequently experienced pulmonary embolism due to cancer progression.•Pericardial and pleural effusion were successfully treated using bevacizumab.

11.
Acute Med Surg ; 3(2): 155-158, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-29123771

RESUMO

Case: We have reported six cases of Crowned dens syndrome (CDS) diagnosed by computed tomography (CT). Presenting cases were three male and three female, aged from 45 to 89 (averaged in 72). Outcome: All cases showed calcification around the dens of axis in CTs. Neck pain in all cases relieved within at least 10 days, treated by non-steroidal anti-inflammatory drugs (NSAIDs) in five cases, and one by acetaminophens. Conclusion: Bouvet et al. first reported CDS in 1985, as acute pseudogout of the neck, which causes neck pain. CDS is a radioclinical syndrome defined by the radiographic calcifications in a crown-like configuration around the odontoid process, accompanied clinically by acute neck pain, often with neck stiffness, fevers and raised inflammatory markers. CDS is thought to be a rare condition; however, it is frequently misdiagnosed. CDS is an important differential diagnosis in patients presenting with acute neck pain.

12.
J Biochem ; 159(2): 201-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26330566

RESUMO

Small GTPases play important roles in various aspects of cell division as well as membrane trafficking. We and others previously showed that ADP-ribosylation factor 6 (Arf6) is locally activated around the ingressing cleavage furrow and recruited to the Flemming body in late cytokinesis phases, and involved in faithful completion of cytokinesis. However, knockout of the Arf6 gene or Arf6 depletion by siRNAs did not drastically influence cytokinesis. We here show that, in addition to Arf6, Class I Arfs (Arf1 and Arf3) are localized to the Flemming body, and that double knockdown of Arf1 and Arf3 moderately increases the proportion of multinucleate cells and simultaneous knockdown of Arf1, Arf3 and Arf6 leads to severe cytokinesis defects. These observations indicate that Arf1 and Arf3 as well as Arf6 play important roles in cytokinesis. We further show that EFA6 (exchange factor for Arf6) activates not only Arf6 but also Arf1 in the cell. Taken together with our previous data, these Arf GTPases are likely to be locally activated by EFA6 and in turn targeted to the Flemming body to complete cytokinesis.


Assuntos
Fator 1 de Ribosilação do ADP/metabolismo , Fatores de Ribosilação do ADP/metabolismo , Citocinese , Proteínas do Tecido Nervoso/metabolismo , Fator 1 de Ribosilação do ADP/genética , Fatores de Ribosilação do ADP/genética , Técnicas de Silenciamento de Genes , Técnicas de Inativação de Genes , Complexo de Golgi , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Células HeLa , Humanos , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética
13.
FEBS Lett ; 587(11): 1617-23, 2013 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-23603394

RESUMO

The small GTPase Arf6 is transiently associated with the ingressing cleavage furrow and subsequently targeted to the Flemming body during cytokinesis, suggesting its activation around the cleavage furrow. Here, we show that EFA6 (exchange factor for Arf6) localizes on the cleavage furrow through its PH domain. Time-lapse analysis showed that both EFA6 and Arf6 are transiently localized around the ingressing cleavage furrow, but only Arf6 is subsequently targeted to the Flemming body. Expression of an EFA6 mutant suppresses Arf6 recruitment onto the Flemming body. These results suggest that EFA6 participates in activation of Arf6 around the cleavage furrow during cytokinesis.


Assuntos
Fatores de Ribosilação do ADP/metabolismo , Citocinese , Proteínas do Tecido Nervoso/metabolismo , Sequência de Aminoácidos , Substituição de Aminoácidos , Sequência Conservada , Ativação Enzimática , Fatores de Troca do Nucleotídeo Guanina , Células HeLa , Humanos , Microscopia de Fluorescência , Mutagênese Sítio-Dirigida , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/genética , Estrutura Terciária de Proteína , Transporte Proteico , Análise de Célula Única , Imagem com Lapso de Tempo
14.
Cell Struct Funct ; 38(1): 31-41, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23328347

RESUMO

Upon cell division, not only cells themselves but also their organelles undergo drastic shape changes, although the behaviors of organelles other than the Golgi apparatus remain poorly understood. We followed the spatiotemporal changes in the localization of transferrin receptor (TfnR) and other proteins. In early mitotic phases, a population of proteins cycling through the endocytic recycling compartment (ERC) exhibits a distinct spatiotemporal change from that of Golgi proteins. In prophase/prometaphase, when the cell surface-to-volume ratio is reaching its minimum, the ERC proteins are transiently assembled around the centrated centrosome in a microtubule- and dynein-dependent manner, and soon separated polewards into two clusters concomitant with separation of duplicated centrosomes. Electron microscopic analysis revealed that endosomal vesicles containing endocytosed transferrin cluster tightly around centrosomes without fusing with one another. As cytokinesis proceeds, the clusters gradually collapse, and the ERC proteins reassemble around the furrowing equatorial region. FRAP (fluorescence recovery after photobleaching) analyses of EGFP-TfnR-expressing cells revealed minimal membrane exchange between the endosomal clusters and other cellular compartments until anaphase/telophase, when membrane traffic resumes. Our observations indicate that ERC clustering around centrosomes plays a fundamental role in restricting membrane delivery to the plasma membrane during early mitotic phases, when the cell surface-to-volume ratio reaches its minimum.


Assuntos
Centrossomo , Endossomos , Microtúbulos , Mitose , Anáfase , Membrana Celular/metabolismo , Centrossomo/metabolismo , Centrossomo/ultraestrutura , Citocinese/genética , Endocitose/genética , Endossomos/metabolismo , Endossomos/ultraestrutura , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Proteínas de Membrana Transportadoras/metabolismo , Microtúbulos/metabolismo , Microtúbulos/ultraestrutura , Mitose/genética , Organelas/metabolismo , Organelas/ultraestrutura , Receptores da Transferrina/análise , Fuso Acromático/ultraestrutura
15.
EMBO J ; 31(11): 2590-603, 2012 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-22522702

RESUMO

A small GTPase, Arf6, is involved in cytokinesis by localizing to the Flemming body (the midbody). However, it remains unknown how Arf6 contributes to cytokinesis. Here, we demonstrate that Arf6 directly interacts with mitotic kinesin-like protein 1 (MKLP1), a Flemming body-localizing protein essential for cytokinesis. The crystal structure of the Arf6-MKLP1 complex reveals that MKLP1 forms a homodimer flanked by two Arf6 molecules, forming a 2:2 heterotetramer containing an extended ß-sheet composed of 22 ß-strands that spans the entire heterotetramer, suitable for interaction with a concave membrane surface at the cleavage furrow. We show that, during cytokinesis, Arf6 is first accumulated around the cleavage furrow and, prior to abscission, recruited onto the Flemming body via interaction with MKLP1. We also show by structure-based mutagenesis and siRNA-mediated knockdowns that the complex formation is required for completion of cytokinesis. A model based on these results suggests that the Arf6-MKLP1 complex plays a crucial role in cytokinesis by connecting the microtubule bundle and membranes at the cleavage plane.


Assuntos
Fatores de Ribosilação do ADP/metabolismo , Citocinese , Proteínas Associadas aos Microtúbulos/metabolismo , Fatores de Ribosilação do ADP/química , Fatores de Ribosilação do ADP/genética , Animais , Cristalografia por Raios X , Células HeLa , Humanos , Camundongos , Proteínas Associadas aos Microtúbulos/química , Proteínas Associadas aos Microtúbulos/genética , Mutação , Ligação Proteica
16.
Retina ; 32(2): 308-13, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21869614

RESUMO

PURPOSE: To report the usefulness of indocyanine green angiography (ICGA) to depict the retinal vascular anomalies associated with distant branch retinal vein occlusion resulting in serous retinal detachment at the macula. METHODS: This was a retrospective, case series of 6 patients (6 eyes) with serous retinal detachments. Fluorescein angiography and ICGA showed that those 6 eyes had a distant branch retinal vein occlusion. The characteristics in ophthalmic examinations such as fundus appearance, fluorescein angiography, ICGA, optical coherence tomography, and clinical courses were evaluated. RESULTS: In addition to serous retinal detachments, five eyes exhibited hard exudates around the macula. Fluorescein angiography and ICGA clearly showed the vessel occlusion; however, no apparent abnormalities appeared in the macular area in any of the eyes. In four eyes, early-phase ICGA depicted the retinal vascular anomalies within the area of venous occlusion and those were seen as hyperfluorescent patches on late-phase ICGA. In two eyes, punctate hyperfluorescent spots were seen in the area of venous occlusion on late-phase ICGA. Optical coherence tomography depicted a serous retinal detachment at the macula and retinal swelling in the outer nuclear layer from the macula to the hyperfluorescent abnormalities on ICGA. The macular serous retinal detachments were resolved within 3 months after laser photocoagulation was applied to the hyperfluorescent areas on ICGA. CONCLUSION: Leakage from subsequent vascular anomalies after branch retinal vein occlusion can cause submacular fluid. Indocyanine green angiography is useful for detecting the causative vascular regions of the fluid.


Assuntos
Corantes , Angiofluoresceinografia , Verde de Indocianina , Descolamento Retiniano/diagnóstico , Oclusão da Veia Retiniana/diagnóstico , Vasos Retinianos/patologia , Idoso , Permeabilidade Capilar , Feminino , Humanos , Fotocoagulação a Laser , Masculino , Pessoa de Meia-Idade , Descolamento Retiniano/etiologia , Oclusão da Veia Retiniana/complicações , Estudos Retrospectivos , Líquido Sub-Retiniano , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia
17.
Invest Ophthalmol Vis Sci ; 52(2): 987-93, 2011 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-20688738

RESUMO

PURPOSE: Ischemia causes severe and persistent visual loss in many eye diseases, including central retinal vein occlusion (CRVO) and diabetic retinopathy. Activated protein C (APC) has been demonstrated to reduce the cell death associated with ischemia in the brain and kidney. This study was performed to examine the ability of APC to rescue hypoxia-induced retinal cell death in vitro and in vivo. METHODS: Retinal pigment epithelium (RPE) and photoreceptor cells were placed in either a normoxic or a hypoxic chamber. Immediately before they were subjected to ischemia, the cultures were treated with APC (3-240 µg/mL). Incubation was followed by an MTT assay to determine the number of viable cells. The activity of caspase-3, -8, and -9 in RPE cells was also analyzed. Various concentrations of APC were intravitreally injected in a rat CRVO model, followed by TUNEL staining to detect the in vivo effects of APC. RESULTS: Lower concentrations of APC (0.3-30 µg/mL) showed a cell-protective effect against hypoxia in vitro, whereas higher concentrations (≥120 µg/mL) demonstrated cytotoxicity in both RPE and photoreceptor cells. Caspase-3, -8, and -9 were activated when the cells were exposed to hypoxia, but this activation was significantly inhibited by APC. Experimental CRVO-induced retinal cell apoptosis was reduced dramatically by intravitreal injection of APC. CONCLUSIONS: APC can reduce ischemia-induced cytotoxicity both in vitro and in vivo via blocking the activation of caspase-3, -8, and -9. APC may be a promising candidate for protecting the retina from ischemia.


Assuntos
Fibrinolíticos/farmacologia , Proteína C/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Células Fotorreceptoras Retinianas Cones/efeitos dos fármacos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Oclusão da Veia Retiniana/prevenção & controle , Animais , Apoptose , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Sobrevivência Celular , Células Cultivadas , Citoproteção , Relação Dose-Resposta a Droga , Humanos , Hipóxia , Marcação In Situ das Extremidades Cortadas , Injeções Intravítreas , Camundongos , Camundongos Transgênicos , Ratos , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/patologia , Células Fotorreceptoras Retinianas Cones/citologia , Células Fotorreceptoras Retinianas Cones/enzimologia , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/enzimologia , Oclusão da Veia Retiniana/enzimologia , Oclusão da Veia Retiniana/patologia
18.
Nihon Kokyuki Gakkai Zasshi ; 44(12): 957-61, 2006 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-17233394

RESUMO

A 38-year-old man with atopic dermatitis presented with right chest pain and dyspnea. Previously, he had received 2mg of betamethasone daily, to prevent rejection of the right transplanted cornea, for 24 days. His body temperature was 37.4 degrees C, peripheral leucocyte count measured 12,000/mm3, and C-reactive protein was 6.3 mg/dl. A computed tomogram of the chest revealed infiltration in the right lower lung field, and he was then treated for pneumonia. The second day he fell down one flight of stairs due to a syncopal attack and received a head injury. At this point his vital blood pressure was 102/55 mmHg, heart rate was 130/min and SpO2 under breathing room air was 76%. These findings indicated possible acute pulmonary thromboembolism. Enhanced computed tomography revealed pulmonary arteries occluded by massive thrombosis and anomalous inferior vena cava with azygous continuation. To decrease the risk of further cerebral bleeding, anti-coagulation therapy was administered with only 24,000 IU/day of heparin. Following treatment, the patient completely recovered. We reported this rare case of acute pulmonary thromboembolism accompanied by anomalous inferior vena cava with azygous continuation.


Assuntos
Veia Ázigos/anormalidades , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico por imagem , Veia Cava Inferior/anormalidades , Doença Aguda , Adulto , Anticoagulantes/uso terapêutico , Heparina/uso terapêutico , Humanos , Masculino , Embolia Pulmonar/tratamento farmacológico , Tomografia Computadorizada por Raios X
19.
J Mass Spectrom ; 39(2): 202-7, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14991690

RESUMO

Mass spectrometry (MS) together with genome database searches serves as a powerful tool for the identification of proteins. In proteome analysis, mixtures of cellular proteins are usually separated by sodium dodecyl sulfate (SDS) polyacrylamide gel-based two-dimensional gel electrophoresis (2-DE) or one-dimensional gel electrophoresis (1-DE), and in-gel digested by a specific protease. In-gel protein digestion is one of the critical steps for sensitive protein identification by these procedures. Efficient protein digestion is required for obtaining peptide peaks necessary for protein identification by MS. This paper reports a remarkable improvement of protein digestion in SDS polyacrylamide gels using an acid-labile surfactant, sodium 3-[(2-methyl-2-undecyl-1,3-dioxolan-4-yl)methoxy]-1-propanesulfonate (ALS). Pretreatment of gel pieces containing protein spots separated by 2-DE with a small amount of ALS prior to trypsin digestion led to increases in the digested peptides eluted from the gels. Consistently, treatment of gel pieces containing silver-stained standard proteins and those separated from tissue extracts resulted in the detection of increased numbers of peptide peaks in spectra obtained by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOFMS). Hence the present protocol with ALS provides a useful strategy for sensitive protein identification by MS.


Assuntos
Alcanossulfonatos/química , Eletroforese em Gel Bidimensional/métodos , Mapeamento de Peptídeos/métodos , Dodecilsulfato de Sódio/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Tensoativos/química , Animais , Células Cultivadas , Proteômica/métodos , Ratos
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