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Objective: To investigate the effects of metformin on mitochondrial pathway of apoptosis and oxidative stress in cell model of nonalcoholic fatty liver disease. Methods: An in vitro cell model of nonalcoholic fatty liver disease was established using 0.6 mmol/L oleic acid to induce lipid accumulation in HepG2 cells. HepG2 cells were divided into control (Con) group, oleic acid (OA) group, and metformin-low (1mmol/L) and high (10mmol/L) dose group. Oil Red O stain was used to detect intracellular lipid droplet distribution. The levels of alanine aminotransferase and aspartate aminotransferase in the culture supernatant were detected by assay kits. DCFH-DA method was used to detect the reactive oxygen species of HepG2 cells. Double staining flow cytometry was used to detect the apoptosis rate of HepG2 cells. Western blot was used to detect caspase-3, B-lymphocyte lymphoma-related protein, B-cell lymphoma 2, and cytochrome c protein. One-way analysis of variance was used to compare the data between groups. Results: Oleic acid-induced HepG2 cells were significantly increased with lipid droplets. Low and high-dose metformin had reduced intracellular lipid droplets accumulation. The effect of metformin in the high-dose group was more significant than that in the low-dose group. Aspartate aminotransferase and alanine aminotransferase in HepG2 cells of OA group were significantly increased, which were (43.41 ± 7.11) U/L and (29.56 ± 4.11) U/L, respectively. The intracellular aspartate aminotransferase and alanine aminotransferase were decreased significantly after the treatment with low and high-dose metformin, which were (32.44 ± 4.08)U/L, (19.31 ± 3.03) U/L, (26.00 ± 3.11) U/L and (15.11 ± 4.11) U/L, respectively and the differences were statistically significant (P < 0.05). DCFH-DA test results showed that the fluorescence intensity of reactive oxygen species in the oleic acid group was 41.21% ± 4.23%, while the fluorescence intensity of reactive oxygen species in the low and high-dose metformin groups were reduced to 27.44% ± 3.91%, and 17.55% ± 5.11%, respectively and the differences between the groups were statistically significant (P < 0.05). The results of flow cytometry analysis showed that the cell apoptosis rate of the OA group was significantly higher than that of the Con group (12.12% ± 0.72% vs. 3.04% ± 0.57%, P < 0.05).The apoptosis rate of HepG2 cells was significantly reduced after metformin treatment at low and high doses (8.71% ± 0.71%, 5.71% ± 0.61%, P < 0.05). Western blot results showed that compared with the Con group, the expressions of B-lymphocyte lymphoma-related protein, cytochrome c, and caspase-3 were increased in the OA group, while the B-cell lymphoma 2 were decreased (P < 0.05). The expression of B-lymphocyte lymphoma-related protein, cytochrome c, and caspase-3 protein in HepG2 cells was decreased after treatment with low and high-dose metformin, while B-cell lymphoma 2 was increased (P < 0.05). Conclusion: Metformin can effectively alleviate steatosis and improve the HepG2 function in cell model of nonalcoholic fatty liver disease. The mechanism of metformin may be related to the reduction of oxidative stress injury, the regulation of protein expression related to mitochondrial apoptosis pathway and the inhibition of cell apoptosis.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Estresse Oxidativo , Apoptose , Células Hep G2 , Humanos , Metformina , MitocôndriasRESUMO
Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.
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Febre Familiar do Mediterrâneo , Doenças Hereditárias Autoinflamatórias , Masculino , Criança , Feminino , Humanos , Pré-Escolar , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Estudos Retrospectivos , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/genética , Doenças Hereditárias Autoinflamatórias/tratamento farmacológico , Glucocorticoides/uso terapêutico , Fatores Biológicos/uso terapêutico , Imunossupressores/uso terapêutico , Autoanticorpos , Febre Familiar do Mediterrâneo/diagnóstico , MutaçãoRESUMO
We develop a rigorous quantum mechanical theory for collisions of polyatomic molecular radicals with S-state atoms in the presence of an external magnetic field. The theory is based on a fully uncoupled space-fixed basis set representation of the multichannel scattering wave function. Explicit expressions are presented for the matrix elements of the scattering Hamiltonian for spin-1/2 and spin-1 polyatomic molecular radicals interacting with structureless targets. The theory is applied to calculate the cross sections and thermal rate constants for spin relaxation in low-temperature collisions of the prototypical organic molecule methylene [CH(2)(X(3)B(1))] with He atoms. To this end, two accurate three-dimensional potential energy surfaces (PESs) of the He-CH(2)(X(3)B(1)) complex are developed using the state-of-the-art coupled-cluster method including single and double excitations along with a perturbative correction for triple excitations and large basis sets. Both PESs exhibit shallow minima and are weakly anisotropic. Our calculations show that spin relaxation in collisions of CH(2), CHD, and CD(2) molecules with He atoms occurs at a much slower rate than elastic scattering over a large range of temperatures (1 µK-1 K) and magnetic fields (0.01-1 T), suggesting excellent prospects for cryogenic helium buffer-gas cooling of ground-state ortho-CH(2)(X(3)B(1)) molecules in a magnetic trap. Furthermore, we find that ortho-CH(2) undergoes collision-induced spin relaxation much more slowly than para-CH(2), which indicates that magnetic trapping can be used to separate nuclear spin isomers of open-shell polyatomic molecules.
RESUMO
We present a rigorous theoretical study of low-temperature collisions of polyatomic molecular radicals with (1)S(0) atoms in the presence of an external magnetic field. Accurate quantum scattering calculations based on ab initio and scaled interaction potentials show that collision-induced spin relaxation of the prototypical organic molecule CH(2)(X(3)B(1)) (methylene) and nine other triatomic radicals in cold (3)He gas occurs at a slow rate, demonstrating that cryogenic buffer-gas cooling and magnetic trapping of these molecules is feasible with current technology. Our calculations further suggest that it may be possible to create ultracold gases of polyatomic molecules by sympathetic cooling with alkaline-earth atoms in a magnetic trap.
RESUMO
Kinetochores can be thought of as having three major functions in chromosome segregation: (a) moving plateward at prometaphase; (b) participating in spindle checkpoint control; and (c) moving poleward at anaphase. Normally, kinetochores cooperate with opposed sister kinetochores (mitosis, meiosis II) or paired homologous kinetochores (meiosis I) to carry out these functions. Here we exploit three- and four-dimensional light microscopy and the maize meiotic mutant absence of first division 1 (afd1) to investigate the properties of single kinetochores. As an outcome of premature sister kinetochore separation in afd1 meiocytes, all of the chromosomes at meiosis II carry single kinetochores. Approximately 60% of the single kinetochore chromosomes align at the spindle equator during prometaphase/metaphase II, whereas acentric fragments, also generated by afd1, fail to align at the equator. Immunocytochemistry suggests that the plateward movement occurs in part because the single kinetochores separate into half kinetochore units. Single kinetochores stain positive for spindle checkpoint proteins during prometaphase, but lose their staining as tension is applied to the half kinetochores. At anaphase, approximately 6% of the kinetochores develop stable interactions with microtubules (kinetochore fibers) from both spindle poles. Our data indicate that maize meiotic kinetochores are plastic, redundant structures that can carry out each of their major functions in duplicate.
Assuntos
Segregação de Cromossomos , Cinetocoros , Meiose/genética , Zea mays/genética , Fenômenos Biomecânicos , Cromátides , Cinetocoros/ultraestrutura , Microtúbulos , Mitose , Movimento , Mutação , Proteínas de Plantas/metabolismo , Fuso Acromático , Zea mays/ultraestruturaRESUMO
We have identified a maize homologue of yeast MAD2, an essential component in the spindle checkpoint pathway that ensures metaphase is complete before anaphase begins. Combined immunolocalization of MAD2 and a recently cloned maize CENPC homologue indicates that MAD2 localizes to an outer domain of the prometaphase kinetochore. MAD2 staining was primarily observed on mitotic kinetochores that lacked attached microtubules; i.e., at prometaphase or when the microtubules were depolymerized with oryzalin. In contrast, the loss of MAD2 staining in meiosis was not correlated with initial microtubule attachment but was correlated with a measure of tension: the distance between homologous or sister kinetochores (in meiosis I and II, respectively). Further, the tension-sensitive 3F3/2 phosphoepitope colocalized, and was lost concomitantly, with MAD2 staining at the meiotic kinetochore. The mechanism of spindle assembly (discussed here with respect to maize mitosis and meiosis) is likely to affect the relative contributions of attachment and tension. We support the idea that MAD2 is attachment-sensitive and that tension stabilizes microtubule attachments.
Assuntos
Proteínas de Ligação ao Cálcio/genética , Proteínas de Transporte , Sequência Conservada , Proteínas Fúngicas/genética , Meiose/fisiologia , Mitose/fisiologia , Zea mays/genética , Anáfase/fisiologia , Anticorpos , Proteínas de Ligação ao Cálcio/análise , Proteínas de Ligação ao Cálcio/imunologia , Proteínas de Ciclo Celular , Células Eucarióticas/química , Células Eucarióticas/citologia , Células Eucarióticas/fisiologia , Proteínas Fúngicas/análise , Proteínas Fúngicas/imunologia , Imuno-Histoquímica , Cinetocoros/química , Cinetocoros/fisiologia , Metáfase/fisiologia , Microtúbulos/metabolismo , Dados de Sequência Molecular , Proteínas Nucleares , Proteínas de Plantas/análise , Proteínas de Plantas/genética , Proteínas de Plantas/imunologia , Homologia de Sequência de Aminoácidos , Fuso Acromático/química , Fuso Acromático/fisiologia , Coloração e Rotulagem , Estresse MecânicoRESUMO
Neocentromere activity is a classic example of nonkinetochore chromosome movement. In maize, neocentromeres are induced by a gene or genes on Abnormal chromosome 10 (Ab10) which causes heterochromatic knobs to move poleward at meiotic anaphase. Here we describe experiments that test how neocentromere activity affects the function of linked centromere/kinetochores (kinetochores) and whether neocentromeres and kinetochores are mobilized on the spindle by the same mechanism. Using a newly developed system for observing meiotic chromosome congression and segregation in living maize cells, we show that neocentromeres are active from prometaphase through anaphase. During mid-anaphase, normal chromosomes move on the spindle at an average rate of 0.79 micron/min. The presence of Ab10 does not affect the rate of normal chromosome movement but propels neocentromeres poleward at rates as high as 1.4 micron/min. Kinetochore-mediated chromosome movement is only marginally affected by the activity of a linked neocentromere. Combined in situ hybridization/immunocytochemistry is used to demonstrate that unlike kinetochores, neocentromeres associate laterally with microtubules and that neocentromere movement is correlated with knob size. These data suggest that microtubule depolymerization is not required for neocentromere motility. We argue that neocentromeres are mobilized on microtubules by the activity of minus end-directed motor proteins that interact either directly or indirectly with knob DNA sequences.
Assuntos
Centrômero/fisiologia , Cromossomos/fisiologia , Meiose , Anáfase , Cinetocoros/fisiologia , Microtúbulos/fisiologia , Fuso Acromático/fisiologia , Zea maysRESUMO
BACKGROUND: Gastrointestinal (GI) lipomas are benign, slowly growing, submucosal tumors, which may cause gastrointestinal bleeding, anemia, intussusception, and bowel obstruction. The aim of this study is to explore the safe and effective strategy for endoscopic removal of large GI lipomas. METHODS: During last 10 years, fifteen large and symptomatic GI lipomas were resected under endoscopy in our hospital. In them, two large lipomas with small stalk (< 2 m in diameter) were resected by polypectomy; ten large lipomas with base size greater than 2 cm in diameter were removed using a "subtotal resection." Three other large lipomas with small stalk (< 2 m in diameter) were resected by multistep resection. Endoscopic ultrasonography (EUS) and miniprobe endoscopic ultrasound were performed in six cases from January 2000 to July 2004 to confirm that those lesions were lipomas that were superficial to the muscularis propria. RESULTS: All 15 lesions were successfully removed and were histopathologically confirmed to be lipomas. No severe complications, such as perforation or hemorrhage, developed after endoscopic removal. No recurrence was observed after 1-8 years follow-up endoscopic examination. CONCLUSIONS: Various, large GI lipomas can be removed safely by electrosurgical snare resection under endoscopy following the guidance of the present therapeutic strategy.
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Endoscopia Gastrointestinal/métodos , Neoplasias Gastrointestinais/cirurgia , Lipoma/cirurgia , Adulto , Idoso , Endoscopia Gastrointestinal/efeitos adversos , Endossonografia , Feminino , Seguimentos , Neoplasias Gastrointestinais/diagnóstico por imagem , Neoplasias Gastrointestinais/patologia , Humanos , Lipoma/diagnóstico por imagem , Lipoma/patologia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Complicações Pós-Operatórias/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
AIMS: To identify whether phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase/extracellular-regulated protein kinases signalling pathways are implicated in the chemoresistance of gastric cancer and to explore the possible mechanisms. METHODS: Gastric cancer cell lines SGC7901 and BGC823 were exposed to etoposide, Wortmannin+etoposide or PD98059+etoposide. Cell cycle distribution and cell apoptosis were detected using flow cytometry and Hoechst 33258 staining. Cells viability was determined by a colourimetric assay utilising 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). Akt activity was detected using non-radioactive immunoprecipitation-kinase assay. Western blotting was exploited to evaluate the level of phosphorylated ERK1/2 and expressions of c-Myc and p53 protein. RESULTS: Etoposide suppressed the viability of SGC7901 and BGC823 cells in a time- and dose-dependent manner; PD98059 and Wortmannin were able to enhance the cytotoxicity of etoposide. The apoptotic levels of cells treated with Wortmannin+etoposide or PD98059+etoposide were significantly higher than those of cells treated with etoposide only. Phospho-ERK1/2, Akt activity and expression of c-Myc were significantly induced by etoposide in a time-dependent manner; moreover, there was a weak effect on the expression of p53 protein. Both Wortmannin and PD98059 elevated the level of p53 expression strikingly, however, only PD98059 suppressed the up-regulation trend of c-Myc expression induced by etoposide. CONCLUSION: Chemotherapy reagent activated phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase/extracellular-regulated protein kinases signalling pathways, which decreased the chemotherapy sensitivity of gastric cancer cell lines SGC7901 and BGC823 via suppressing the expression of p53 and enhancing the expression of c-Myc. This may be one of the molecular mechanisms of gastric cancer chemoresistance.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Etoposídeo/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Androstadienos/farmacologia , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ativação Enzimática/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Flavonoides/farmacologia , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Neoplasias Gástricas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , WortmaninaRESUMO
Kinetochores are large protein complexes that bind to centromeres. By interacting with microtubules and their associated motor proteins, kinetochores both generate and regulate chromosome movement. Kinetochores also function in the spindle checkpoint; a surveillance mechanism that ensures that metaphase is complete before anaphase begins. Although the ultrastructure of plant kinetochores has been known for many years, only recently have specific kinetochore proteins been identified. The recent data indicate that plant kinetochores contain homologs of many of the proteins implicated in animal and fungal kinetochore function, and that the plant kinetochore is a redundant structure with distinct biochemical subdomains.
Assuntos
Cinetocoros , Plantas/metabolismo , Sequência de Aminoácidos , Animais , Humanos , Cinetocoros/química , Dados de Sequência Molecular , Homologia de Sequência de AminoácidosRESUMO
Continuous experiments were conducted to study the influence of pH in the range 4.0-6.5 on the acidification of dairy wastewater at 37 degrees C with 12 hours of hydraulic retention in an upflow reactor. Results showed that degradation of dairy pollutants increased with pH from pH 4.0 to 5.5. At pH 5.5, 95% of carbohydrate, 82% of protein and 41% of lipid were degraded. Based on chemical oxygen demand (COD), 48.4% of dairy pollutants were converted into volatile fatty acids and alcohols in the mixed liquor, 6.1% into hydrogen and methane in biogas, and the remaining 4.9% into biomass. The biomass yield at pH 5.5 was estimated as 0.32 mg-VSS/mg-COD. Further increase of pH, up to 6.5, increased degradation of carbohydrate, protein and lipid only slightly, but resulted in the lowering of overall acid and alcohol production due to their increased conversion into methane. Acetate, propionate, butyrate and ethanol are the main products of acidogenesis. Productions of propionate and ethanol were favored at pH 4.0-4.5, whereas productions of acetate and butyrate were favored at pH 6.0-6.5.
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Ácidos/análise , Agricultura , Reatores Biológicos , Eliminação de Resíduos Líquidos/métodos , Animais , Biomassa , Bovinos , Ácidos Graxos/análise , Concentração de Íons de Hidrogênio , VolatilizaçãoRESUMO
To determine surgical results and predictive factors of final visual acuity, a total of 30 eyes in 30 uveitis patients who underwent vitreous surgery including pars plana vitrectomy were followed for at least 6 months and various preoperative factors and postoperative results were analyzed. Our surgical indications were vitreous opacity, traction retinal detachment, combined rhegmatogenous-traction detachment. Preoperatively detached retina was finally reattached in 15 (83.3%) of 18 eyes. Final visual acuity improved in 19 (63.3%) of 30 eyes, but decreased in 3 eyes compared with the initial acuity. Cystoid macular edema was the main cause of poor visual acuity after surgery. Eyes with good final visual acuity showed relatively normal electroretinograms before surgery, but the relationship between them was not statistically significant. Duration of postoperative inflammation affected final visual acuity significantly. These results suggest that chronic uveitis patients with vitreoretinal complications can be managed by vitreous surgery with good anatomic and functional results.
Assuntos
Doenças Retinianas/cirurgia , Uveíte/complicações , Vitrectomia , Corpo Vítreo/cirurgia , Adolescente , Adulto , Criança , Doença Crônica , Oftalmopatias/etiologia , Oftalmopatias/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Doenças Retinianas/etiologia , Acuidade VisualRESUMO
To investigate the therapeutic potential of mitomycin C (MMC) in the management of proliferative vitreoretinopathy (PVR), antiproliferative effect of MMC on rabbit retinal pigment epithelial (RPE) cells, its intraocular toxicity, and its preventive effect on experimental PVR were investigated. Cultured rabbit RPE cells were exposed to various concentrations of MMC ranging from 1.0 x 10(-3) to 1.0 microgram/ml for 72 hours. The RPE cells were then cultured in a medium without MMC for another 7 days, and the cells were harvested and counted. Toxicity of MMC to rabbit retina was evaluated after intravitreal injection of MMC by means of clinical observation, electrophysiologic test, and histopathologic examination. To test antiproliferative effect of MMC on experimental PVR, 200,000 cultured RPE cells were injected into the vitreous cavity of pigmented rabbits, and either 0.2 micrograms or 1.0 micrograms MMC was injected intravitreally 24 hours after RPE cell injection. Two to four weeks later, the vitreoretinal status was compared between MMC-treated eyes and control eyes. The antiproliferative effect of MMC on RPE cells was evident at the concentration of 1.0 x 10(-2) micrograms/ml. The drug concentration required for 50% inhibition of growth was 3 x 10(-2) micrograms/ml. Nontoxic intraocular doses of MMC were 2.0 micrograms in rabbit eyes with normal vitreous and 1.0 microgram in rabbit eyes with gas-compressed vitreous. The rates of traction retinal detachment after intravitreal RPE cell injection were reduced in the eyes treated with MMC compared with control eyes. These results indicate that MMC may have clinical application to the treatment of PVR.
Assuntos
Mitomicina/farmacologia , Inibidores da Síntese de Ácido Nucleico/farmacologia , Vitreorretinopatia Proliferativa/prevenção & controle , Animais , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Seguimentos , Injeções , Epitélio Pigmentado Ocular/efeitos dos fármacos , Coelhos , Vitreorretinopatia Proliferativa/patologia , Corpo VítreoRESUMO
Cryotherapy has been shown to be an effective treatment for retinopathy of prematurity (ROP) stage 3+. However, the outcome of cryotherapy is less favorable in zone 1 ROP than in zone 2 ROP. We suspected whether there may be differences in the outcomes of cryotherapy if the zone of ROP is further divided. So we reviewed the records of 85 premature infants (145 eyes) who had undergone cryotherapy for ROP. The frequencies of favorable outcome were 42.9% of 14 eyes (zone 1), 78.9% of 38 eyes (posterior zone 2), 92.9% of 70 eyes (mid zone 2), and 100.0% of 23 eyes (anterior zone 2), respectively (p < 0.001). These results suggest that the more posteriorly the ROP is located, the less favorable the outcome of cryotherapy.
Assuntos
Crioterapia/métodos , Retinopatia da Prematuridade/terapia , Seguimentos , Humanos , Lactente , Recém-Nascido , Complicações Pós-Operatórias , Retinopatia da Prematuridade/patologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
To investigate the chronological change of refraction in premature infants after cryotherapy for retinopathy of prematurity (ROP), cycloplegic refractions had been performed at 6 months and 3 years after term in premature infants who underwent cryotherapy for ROP. The changes of refractions between the two study ages were evaluated not only in the total cryo-treated eyes, but also in the subdivided groups according to the posterior pole appearances. In the total 61 eyes of 32 premature infants, mean spherical equivalents were -4.05D vs. -5.94D (6 months vs. 3 years) (p = 0.0001). In the normal posterior pole group (48 eyes), mean spherical equivalents were -3.45D vs. -5.68D (6 months vs. 3 years) (p = 0.0000), and in the abnormal posterior pole group (13 eyes), -6.28D vs. -6.86D (6 months vs. 3 years) (p = 0.6496). These results mean that there is a myopic progressive change between 6 months and 3 years after term in the cryo-treated eyes for acute ROP and it is more evident in the eyes with normal posterior pole.
Assuntos
Criocirurgia/efeitos adversos , Recém-Nascido Prematuro , Miopia/etiologia , Refração Ocular , Retinopatia da Prematuridade/cirurgia , Doença Aguda , Pré-Escolar , Seguimentos , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Miopia/fisiopatologia , Retinopatia da Prematuridade/fisiopatologiaRESUMO
The visual results of laser photocoagulation for subfoveal choroidal neovascular membrane (CNVM) has not always been satisfactory. The surgical removal of the neovascular membrane may be another treatment option. To investigate the prognosis and risk factors of this surgery, we analyzed the results of surgical removal of subfoveal CNVM (23 eyes), subfoveal hemorrhage with CNVM (6 eyes), and subfoveal hemorrhage alone (6 eyes). The mean follow-up period was 17.7 months (range 2 to 47 months). The mean preoperative membrane size was 0.89 disc diameter and the mean postoperative retinal pigment epithelial (RPE) defect size was 1.33 disc diameter. Visual improvement was observed in 13 out of the 23 eyes (56.5%) with sufoveal CNVM, four out of the six eyes (66.6%) with subretinal hemorrhage and CNVM, and five out of the six eyes (83.3%) with subretinal hemorrhage only. The visual outcome of subfoveal CNVM surgery was related to the presence of a subfoveal RPE defect (p = 0.005) rather than to the size of the RPE defect. No recurrence of neovascular membrane was observed during the follow up period. In conclusion, surgical removal may be a good alternative treatment for subfoveal CNVM.
Assuntos
Neovascularização de Coroide/cirurgia , Fotocoagulação a Laser , Neovascularização de Coroide/complicações , Neovascularização de Coroide/diagnóstico , Feminino , Angiofluoresceinografia , Fóvea Central/patologia , Fóvea Central/cirurgia , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Epitélio Pigmentado Ocular/patologia , Prognóstico , Hemorragia Retiniana/complicações , Hemorragia Retiniana/diagnóstico , Hemorragia Retiniana/cirurgia , Estudos Retrospectivos , Fatores de Risco , Acuidade VisualRESUMO
PURPOSE: This randomized phase II study was conducted to compare the efficacy and safety of paclitaxel with S-1 (PS) vs. S-1 in patients with advanced gastric cancer (AGC). METHODS: Eighty-two (82) patients were 1:1 randomly assigned to oral S-1 (daily for 2 weeks, every 4 weeks' cycle) or S-1 (daily for 2 weeks, every 4 weeks' cycle) plus paclitaxel (on day 1, 8 and 15 of a 4 weeks' cycle). S-1 was orally administered with a fixed quantity according to body surface area (BSA), while paclitaxel was given 60 mg/m(2) i.v. daily through an implanted catheter. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall responsible rates and safety. RESULTS: The median OS with PS versus S-1 monotherapy was 14.0 versus 11.0 months (P = 0.02), survival at 12 months was 61.0 % in the PS group and 46.3 % in the S-1 group. Median PFS was also significantly longer in the PS group (6.0 months) than in the S-1 group (4.0 months). The overall response rate was determined in 82 evaluable patients, and was significantly higher (P = 0.04) with PS (19 patients, 46.3 %) than with S-1 monotherapy (10 patients, 24.4 %). PS was well tolerated with no treatment-related deaths, all were grade 3-4 gastrointestinal toxicities, including anorexia, nausea, and diarrhea developed in less than 10 % of the patients. CONCLUSIONS: Combination chemotherapy of paclitaxel with S-1 is well tolerated and active in AGC patients. Further investigation with comparative trials is needed for confirmation.
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Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hepáticas/mortalidade , Neoplasias Peritoneais/mortalidade , Neoplasias Gástricas/mortalidade , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Combinação de Medicamentos , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ácido Oxônico/administração & dosagem , Paclitaxel/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Prognóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Tegafur/administração & dosagem , Adulto JovemRESUMO
The inherent resistance of tumors to DNA damage often limits the efficacy of chemotherapy. The aim of this work is to explore the potential mechanism for development of chemoresistance in gastric cancer. Our data revealed that AKT1 mRNA and protein expression were induced by doxorubicin (a chemotherapeutic agent); the doxorubicin-induced AKT1 expression and activation increased the binding of NF-kappaB on Notch1 DNA promoter and then promoted the Notch1 transcription and expression; enhanced expression of Notch1 further upregulated PTEN expression through CBF-1 binding to PTEN DNA promoter; and inhibition of AKT1 expression and activity sensitized the gastric cancer cell to doxorubicin treatment in cultured gastric cancer cell lines and xenograft nude mice gastric cancer model. Furthermore, our data demonstrated that both Notch1 and PTEN were absent or minimally expressed in gastric cancer tissue but abundant in paired normal gastric mucosa, and the expression of Notch1 correlated with that of PTEN. Together, these novel results suggested that a novel AKT1/NF-kappaB/Notch1/PTEN axis has an important role in the development of chemoresistance in gastric cancer. Notch1 has an anti-cancer role in gastric cancer.
Assuntos
Resistencia a Medicamentos Antineoplásicos , NF-kappa B/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor Notch1/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Sequência de Bases , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Masculino , Camundongos , Camundongos Nus , Dados de Sequência Molecular , PTEN Fosfo-Hidrolase/genética , Regiões Promotoras Genéticas/genética , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/genética , Proteínas Proto-Oncogênicas c-akt/genética , Receptor Notch1/genética , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Fator de Transcrição RelA/metabolismo , Transcrição Gênica/efeitos dos fármacosRESUMO
PURPOSE: To determine whether horizontal macular contraction caused by epiretinal membranes (ERMs) improves after surgical removal. METHODS: In this prospective, single-center, observational study, 63 consecutive patients with unilateral idiopathic ERM in one eye and no retinal disease in the fellow eye underwent pars plana vitrectomy. Fundus photography and optical coherence tomography (OCT) were performed preoperatively and at 3 months postoperatively. The area enclosed by superior and inferior major vessels from the optic disc to the fovea (area under major vessel (AUV)) and the macroscopic diverging angle (MDA) between superior and inferior major vessels were calculated using digital image analysis of fundus photographs and compared pre- and postoperatively. RESULTS: AUV was significantly smaller in the eyes with ERM compared with the normal fellow eyes (P<0.001). Significant postoperative change in AUV and MDA was demonstrated after ERM removal (P<0.001). However, postoperative AUV of grade 2 and 3 ERM eyes was still significantly smaller than that of normal fellow eyes. Macular thickness differences measured with stratus OCT were positively correlated with AUV differences. CONCLUSIONS: Retinal topographic changes caused by ERM improved in part after ERM removal. The improvement of topographic changes were correlated with tomographic changes detected with OCT.
Assuntos
Membrana Epirretiniana/cirurgia , Macula Lutea/patologia , Vitrectomia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Afacia Pós-Catarata , Membrana Epirretiniana/complicações , Membrana Epirretiniana/fisiopatologia , Feminino , Fundo de Olho , Humanos , Macula Lutea/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia de Coerência Óptica , Acuidade VisualRESUMO
PURPOSE: To report two cases of Serratia marcescens endophthalmitis related to presumed aliquot drug contamination, and to determine the incidence of acute endophthalmitis after intravitreal injection of bevacizumab. METHODS: A retrospective chart review of 2020 consecutive intravitreal bevacizumab injection (IVBI) cases at the three affiliated hospitals of Seoul National University (A, B, and C) was carried out between 12 October 2006, and 31 January 2008. Bevacizumab was retrieved multiple times from a single original vial as needed and then discarded on the same day at hospital A and C, or prepared as a single dose aliquot vial at a compounding pharmacy in the hospital B. RESULTS: The incidence of endophthalmitis after IVBI was 2/2020 (0.099%). Two patients receiving IVBI on the same day, but by different surgeons in different sites in hospital B, developed acute endophthalmitis. S. marcescens was isolated from the vitreous sample of the two patients. Molecular typing with pulsed field gel electrophoresis showed that the organisms were of the same strain, which suggested that the drug was contaminated at the pharmacy. CONCLUSIONS: Endophthalmitis is a rare complication after IVBI and can be caused by contaminated aliquot drug. Serratia is one of the causative organisms of acute endophthalmitis, which can have devastating consequences, despite the treatment. A compounding pharmacy in a hospital might not be able to guarantee that aliquoted drug is free of contamination for the IVBI.