RESUMO
BACKGROUND: In previous studies, the prevalence of patent foramen ovale (PFO) has been reported to be higher in scuba divers who experienced decompression illness (DCI) than in those who did not. OBJECTIVE: To assess the association between PFO and DCI in scuba divers. DESIGN: Prospective cohort study. SETTING: Tertiary cardiac center in South Korea. PARTICIPANTS: One hundred experienced divers from 13 diving organizations who did more than 50 dives per year. MEASUREMENTS: Participants had transesophageal echocardiography with a saline bubble test to determine the presence of a PFO and were subsequently divided into high- and low-risk groups. They were followed using a self-reported questionnaire while blinded to their PFO status. All of the reported symptoms were adjudicated in a blinded manner. The primary end point of this study was PFO-related DCI. Logistic regression analysis was done to determine the odds ratio of PFO-related DCI. RESULTS: Patent foramen ovale was seen in 68 divers (37 at high risk and 31 at low risk). Patent foramen ovale-related DCI occurred in 12 divers in the PFO group (non-PFO vs. high-risk PFO vs. low-risk PFO: 0 vs. 8.4 vs. 2.0 incidences per 10 000 person-dives; P = 0.001) during a mean follow-up of 28.7 months. Multivariable analysis showed that high-risk PFO was independently associated with an increased risk for PFO-related DCI (odds ratio, 9.34 [95% CI, 1.95 to 44.88]). LIMITATION: The sample size was insufficient to assess the association between low-risk PFO and DCI. CONCLUSION: High-risk PFO was associated with an increased risk for DCI in scuba divers. This finding indicates that divers with high-risk PFO are more susceptible to DCI than what has been previously reported and should consider either refraining from diving or adhering to a conservative diving protocol. PRIMARY FUNDING SOURCE: Sejong Medical Research Institute.
Assuntos
Doença da Descompressão , Forame Oval Patente , Humanos , Forame Oval Patente/complicações , Forame Oval Patente/diagnóstico por imagem , Forame Oval Patente/epidemiologia , Doença da Descompressão/complicações , Doença da Descompressão/epidemiologia , Estudos de Coortes , Estudos Prospectivos , Descompressão/efeitos adversosRESUMO
[This corrects the article on p. 163 in vol. 22, PMID: 29520169.].
RESUMO
PRF001 is a fragmented DNA polymer extracted from the testes of salmon. The purpose of this study was to assess the anti-inflammatory effect of PRF001 in vitro as well as the protective effect of PRF001 intake against arthritis in a rat model. In vitro, cell survival and inflammatory markers after H2O2 treatment to induce cell damage were investigated in CHON-001 cells treated with different concentrations of PRF001. In vivo, osteoarthritis was induced by intra-articular injection of monosodium iodoacetate (MIA) into the knee joints of rats. After consumption of PRF001 (10, 50, or 100 mg/kg) for 4 weeks, inflammatory mediators and cytokines in articular cartilage were investigated. In vitro, the levels of inflammatory markers, IL-1ß, TNF-α, COX-2, iNOS, and PGE2, were significantly suppressed by PRF001 treatment. In vivo, the inflammatory mediators and cytokines, IL-1ß, p-Erk1/2, NF-κB, TNF-α, COX-2, and PGE2, as well as MMP3 and MMP7, which have catabolic activity in chondrocytes, were decreased in the MIA-induced osteoarthritic rats following intake of PRF001. Histological analysis revealed that PRF001 had a protective effect on the articular cartilage. Altogether, these results demonstrated that the anti-inflammatory property of PRF001 contributes to its protective effects in osteoarthritis through deregulating IL-1ß, TNF-α, and subsequent signals, such as p-Erk1/2, NF-κB, COX-2, PGE2, and MMPs.
RESUMO
BACKGROUND AND OBJECTIVES: Gastrointestinal dysfunction is a common non motor symptom in Parkinson's disease (PD). However, the potential association between vitamin D and gastroparesis in PD has not been previously investigated. The aim of this study was to compare vitamin D levels between drug-naive de novo PD patients with normal gastric emptying and those with delayed gastric emptying. METHODS: Fifty-one patients with drug-naive de novo PD and 20 age-matched healthy controls were enrolled in this study. Gastric emptying time (GET) was assessed by scintigraphy, and gastric emptying half-time (T1/2) was determined. The PD patients were divided into a delayed-GET group and a normal-GET group. RESULTS: The serum 25-hydroxyvitamin D3 levels were decreased in the delayed-GET group compared with the normal-GET and control groups (11.59 ± 4.90 vs. 19.43 ± 6.91 and 32.69 ± 4.93, respectively, p < 0.01). In the multivariate model, the serum 25-hydroxyvitamin D3 level was independently associated with delayed gastric emptying in PD patients. CONCLUSIONS: Vitamin D status may be an independent factor for gastric dysmotility in PD. Although the underlying mechanism remains to be characterized, vitamin D status may play a role in the pathogenesis of delayed gastric emptying in drug-naive PD.
Assuntos
Calcifediol/sangue , Esvaziamento Gástrico/fisiologia , Doença de Parkinson/fisiopatologia , Deficiência de Vitamina D/fisiopatologia , Idoso , Análise Química do Sangue , Estudos Transversais , Feminino , Grelina/sangue , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Análise Multivariada , Doença de Parkinson/diagnóstico por imagem , Índice de Gravidade de Doença , Fatores de Tempo , Deficiência de Vitamina D/diagnóstico por imagemRESUMO
Hydrogen sulfide (H2 S) is a potent vasodilator and regulates cardiovascular homeostasis. Furthermore, H2 S has a crucial role in ischemia-reperfusion injuries, especially of the heart, liver, and kidneys. This study indicates that treatment with hydrogen sulfide is able to restore neurological function after ischemic stroke by promoting angiogenesis. Treatment with H2 S augments angiogenesis in the peri-infarct area, and it significantly improves functional outcomes after 2 weeks in a rat MCAO model. H2 S promotes the phosphorylation of AKT and ERK and increases the expression of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1). H2 S-treated rats showed more newly synthesized endothelial cells in the ischemic lesion (2.31-fold, P < 0.01). H2 S-treated astrocytes increased VEGF and Ang-1 expression, and the inhibition of phosphatidylinositide 3-kinase (PI3K)/AKT signaling by LY294002 significantly reduced H2 S-induced VEGF and Ang-1 expression in astrocytes. Finally, H2 S stimulated endothelial cell migration (3.92-fold increase in wound healing assay) and tube formation (3.69-fold increase, P < 0.001) through PI3K/AKT signaling. In conclusion, treatment with H2 S promotes angiogenesis and thereby contributes to improvement of functional outcome after cerebral ischemia. Our findings strongly suggest that H2 S may be of value in regenerative recovery after stroke.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Isquemia Encefálica/complicações , Sulfeto de Hidrogênio/uso terapêutico , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/etiologia , Análise de Variância , Animais , Infarto Encefálico/tratamento farmacológico , Infarto Encefálico/etiologia , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/deficiência , Hipóxia , Marcação In Situ das Extremidades Cortadas , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/etiologia , Proteína Oncogênica v-akt/metabolismo , Ratos , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: Chronic renal insufficiency, diagnosed using creatinine based estimated glomerular filtration rate (GFR) or microalbumiuria, has been associated with the presence of cerebral microbleeds (CMBs). Cystatin C has been shown to be a more sensitive renal indicator than conventional renal markers. Under the assumption that similar pathologic mechanisms of the small vessel exist in the brain and kidney, we hypothesized that the levels of cystatin C may delineate the relationship between CMBs and renal insufficiency by detecting subclinical kidney dysfunction, which may be underestimated by other indicators, and thus reflect the severity of CMBs more accurately. METHODS: Data was prospectively collected for 683 patients with ischemic stroke. The severity of CMBs was categorized by the number of lesions. Patients were divided into quartiles of cystatin C, estimated GFR and microalbumin/creatinine ratios. Ordinal logistic regression analysis was used to examine the association of each renal indicator with CMBs. RESULTS: In models including both quartiles of cystatin C and estimated GFR, only cystatin C quartiles were significant (the highest vs. the lowest, adjusted OR, 1.88; 95% CI 1.05-3.38; p = 0.03) in contrast to estimated GFR (the highest vs. the lowest, adjusted OR, 1.28; 95% CI 0.38-4.36; p = 0.70). A model including both quartiles of cystatin C and microalbumin/creatinine ratio also showed that only cystatin C quartiles was associated with CMBs (the highest vs. the lowest, adjusted OR, 2.06; 95% CI 1.07-3.94; p = 0.03). These associations were also observed in the logistic models using log transformed-cystatin C, albumin/creatinine ratio and estimated GFR as continuous variables. Cystatin C was a significant indicator of deep or infratenorial CMBs, but not strictly lobar CMBs. In addition, cystatin C showed the greatest significance in c-statistics for the presence of CMBs (AUC = 0.73 ± 0.03; 95% CI 0.66-0.76; p = 0.02). CONCLUSION: Cystatin C may be the most sensitive indicator of CMB severity among the renal disease markers.
Assuntos
Hemorragia Cerebral/sangue , Hemorragia Cerebral/patologia , Cistatina C/sangue , Testes de Função Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas/análise , Isquemia Encefálica/sangue , Isquemia Encefálica/complicações , Hemorragia Cerebral/complicações , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/patologia , Adulto JovemRESUMO
Objective: Most prognostic indexes for ischemic stroke mortality lack radiologic information. We aimed to create and validate a deep learning-based mortality prediction model using brain diffusion weighted imaging (DWI), apparent diffusion coefficient (ADC), and clinical factors. Methods: Data from patients with ischemic stroke who admitted to tertiary hospital during acute periods from 2013 to 2019 were collected and split into training (n = 1109), validation (n = 437), and internal test (n = 654). Data from patients from secondary cardiovascular center was used for external test set (n = 507). The algorithm for predicting mortality, based on DWI and ADC (DLP_DWI), was initially trained. Subsequently, important clinical factors were integrated into this model to create the integrated model (DLP_INTG). The performance of DLP_DWI and DLP_INTG was evaluated by using time-dependent area under the receiver operating characteristic curves (TD AUCs) and Harrell concordance index (C-index) at one-year mortality. Results: The TD AUC of DLP_DWI was 0.643 in internal test set, and 0.785 in the external dataset. DLP_INTG had a higher performance at predicting one-year mortality than premise score in internal dataset (TD- AUC: 0.859 vs. 0.746; p = 0.046), and in external dataset (TD- AUC: 0.876 vs. 0.808; p = 0.007). DLP_DWI and DLP_INTG exhibited strong discrimination for the high-risk group for one-year mortality. Interpretation: A deep learning model using brain DWI, ADC and the clinical factors was capable of predicting mortality in patients with ischemic stroke.
RESUMO
BACKGROUND: Perioperative stroke is a severe complication following surgery. To identify patients at risk for perioperative stroke, several prediction models based on the preoperative factors were suggested. Prediction models often focus on preoperative patient characteristics to assess stroke risk. However, most existing models primarily base their predictions on the patient's baseline characteristics before surgery. We aimed to develop a machine-learning model incorporating both pre- and intraoperative variables to predict perioperative stroke. METHODS AND RESULTS: This study included patients who underwent noncardiac surgery at 2 hospitals with the data of 15 752 patients from Seoul National University Hospital used for development and temporal internal validation, and the data of 449 patients from Boramae Medical Center used for external validation. Perioperative stroke was defined as a newly developed ischemic lesion on diffusion-weighted imaging within 30 days of surgery. We developed a prediction model composed of pre- and intraoperative factors (integrated model) and compared it with a model consisting of preoperative features alone (preoperative model). Perioperative stroke developed in 109 (0.69%) patients in the Seoul National University Hospital group and 11 patients (2.45%) in the Boramae Medical Center group. The integrated model demonstrated superior predictive performance with area under the curve values of 0.824 (95% CI, 0.762-0.880) versus 0.584 (95% CI, 0.499-0.667; P<0.001) in the internal validation; and 0.716 (95% CI, 0.560-0.859) versus 0.505 (95% CI, 0.343-0.654; P=0.018) in the external validation, compared to the preoperative model. CONCLUSIONS: We suggest that incorporating intraoperative factors into perioperative stroke prediction models can improve their accuracy.
RESUMO
BACKGROUND: Matrix metalloproteinases (MMPs) 2 and 9 are a group of Zn2+-dependent endopeptidases to remodel the extracellular matrix. The association of these 2 endopeptidases with the development of morphologic changes in nasal polyps was previously described. OBJECTIVE: To determine whether MMP-2, MMP-9, and tissue inhibitor of MMP-1 (TIMP-1) play a role in the recurrence of nasal polyps. METHODS: To compare MMP-2, MMP-9, and TIMP-1 expression in recurrent vs nonrecurrent polyps, nasal polyps (NPs) and recurrent nasal polyps (RNPs) were obtained from 15 NP patients with chronic rhinosinusitis (CRS) undergoing endoscopic sinus surgery (ESS) and 15 RNP patients with CRS undergoing revision ESS. Fifteen specimens of inferior turbinate mucosa from patients undergoing nasal septal surgery were used as control. Through real-time polymerase chain reaction and immunohistochemistry, MMP-2, MMP-9, and TIMP-1 expressions were measured among controls, NP patients, and RNP patients. RESULTS: Expression of MMP-9 messenger RNA in the NP patients was significantly higher than in the controls. In addition, expression of MMP-9 messenger RNA in the RNP patents was significantly increased compared with NP patients. With immunohistochemistry, a more increased expression of MMP-9 was observed in NP patients than controls. Expression of MMP-9 in RNP patients was also significantly high compared with NP patients, particularly in stroma. CONCLUSION: Expression of MMP-9 is increased in NP patients, and it is so more in the mucosa of RNP patients. Increased expression of MMP-9 is particularly found in the stoma of RNP patients, and it may contribute to the recurrence of NP.
Assuntos
Metaloproteinase 9 da Matriz/genética , Pólipos Nasais/genética , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Pólipos Nasais/metabolismo , RNA Mensageiro/metabolismo , Recidiva , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Adulto JovemRESUMO
The pathophysiology of axonal Guillain-Barré syndrome (GBS) is not simple axonal degeneration, but includes reversible conduction failure. Acute motor axonal neuropathy (AMAN) and acute motor conduction block (CB) neuropathy are the two subtypes of pure motor axonal GBS, but their nosologic boundary is still in debate. We investigated clinical and electrophysiological features of 21 consecutive patients with GBS in Korea. Analysis was focused on the presence of CB at intermediate nerve segments (iCB) in pure motor GBS, and its serial changes during the acute phase of disease. Pure motor GBS was common (81%), and iCB was observed in 12 patients with pure motor GBS. Clinical features of pure motor GBS with iCB were distinct from sensorimotor GBS, but similar to pure motor GBS without iCB, characterized by frequent preceding diarrhea, uncommon cranial nerve palsy, and fast recovery. The iCB was not restricted to common entrapment sites, and the distal segments were also commonly involved in the nerves with iCB. The temporal course of iCB was marked by a rapid and often disproportionate increase of proximal and distal amplitudes without remyelinating slow components. Clinical and electrophysiological features of pure motor GBS in patients with iCB suggest that acute motor CB neuropathy may constitute a spectrum of axonal GBS, sharing a common pathomechanism with AMAN.
Assuntos
Síndrome de Guillain-Barré/fisiopatologia , Adolescente , Adulto , Idoso , Axônios/fisiologia , Eletrofisiologia , Feminino , Síndrome de Guillain-Barré/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa/fisiologia , Adulto JovemRESUMO
A 54-year-old man who developed a left homonymous inferior quadrantanopia showed MRI findings of infarction of the proximal portion of the right superior optic radiations and high T2 signal along the entire distal course of the ipsilateral optic radiations consistent with Wallerian degeneration. Frequently reported in other settings, this imaging abnormality has rarely been described in anterior optic radiation lesions.
Assuntos
Lateralidade Funcional , Nervo Óptico/patologia , Degeneração Walleriana/patologia , Hemianopsia/etiologia , Humanos , Infarto/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Campos Visuais/fisiologia , Degeneração Walleriana/complicaçõesRESUMO
BACKGROUND: Oral steroids are recommended for the treatment of nasal polyps (NPs), but prolonged use is avoided because of side effects. Topical steroids can also control NPs without significant complications; however, the response to this is partially successful, and additional therapies are needed to treat glucocorticoid-resistant NPs. Azathioprine (AZA) and its first metabolite 6-mercaptopurine (6-MP) are important immunosuppressants used for the therapy of various diseases. The aim of this study was to investigate the effects of AZA and 6-MP on inflammatory cytokines in organ-cultured NPs. METHODS: NP explants were cultured using an air-liquid interface method. Cultures were maintained in the absence and presence of steroid, AZA, and 6-MP for 72 hours. Elaboration of cytokines tumor necrosis factor alpha (TNF-α), interleukin (IL)-2, IL-4, IL-5, and IL-13 into the supernatant was quantitated using the enzyme-linked immunosorbent assay (ELISA). The messenger RNA (mRNA) expression levels of TNF-α, IL-2, IL-4, IL-5, and IL-13 in cultured mucosa were measured using real-time polymerase chain reaction. Hematoxylin and eosin staining of cultured mucosa was performed to observe inflammatory cells. Immunohistochemistry was done to evaluate the distribution pattern of inflammatory cytokines in NP explants. RESULTS: On histologic examination, less inflammatory cell infiltration was found in NPs treated by steroid, AZA, and 6-MP than in control, but there was no statistical significance (p = 0.218). On immunohistochemistry, IL-13 showed a steady falling tendency in submucosal glands by steroid, AZA, and 6-MP. Expression of TNF-α, IL-2, IL-4, IL-5, and IL-13 mRNA in the NPs treated by steroid, AZA, and 6-MP were significantly lower than those of the control (p < 0.001 for all). By ELISA, IL-2 and IL-13 were significantly lower with topical steroid, AZA, and 6-MP treatment (p = 0.012 and p < 0.001). CONCLUSION: Topical AZT decreases inflammatory cytokines on human NP explants and this could have future therapeutic implications for NPs.
Assuntos
Azatioprina/farmacologia , Citocinas/metabolismo , Imunossupressores/farmacologia , Pólipos Nasais/patologia , Adolescente , Adulto , Citocinas/genética , Feminino , Humanos , Inflamação , Masculino , Mercaptopurina/farmacologia , Pessoa de Meia-Idade , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Pólipos Nasais/metabolismo , Técnicas de Cultura de Órgãos , Adulto JovemRESUMO
OBJECTIVES: We aimed to compare preterm, neurodevelopmentally disordered and healthy full-term children. METHODS: We enrolled 47 children who were born preterm, 40 neurodevelopmentally disordered children, and 80 healthy children as control participants, in order to assess the cognitive functioning and the risk of behavioral problems at the age of 5. Children were assessed using the Korean Wechsler Preschool and Primary Scale of Intelligence-4th edition (K-WPPSI-IV), the Child Behavior Checklist (CBCL), and the Temperament and Character Inventory (TCI). RESULTS: The mean K-WPPSI-IV score of the preterm group was 87.19±17.36, which was significantly higher than that of the neurodevelopmental disorder group (69.98±28.63; p<0.001) but lower than that of the control group (107.74±14.21; p<0.001). The cumulative CBCL scores of the preterm children were not significantly different from those of the control group. Additionally, the TCI scores for reward dependence of the preterm children were higher than those of the control group. CONCLUSION: The cognitive performance of preterm infants was lower than that of healthy full-term infants at the age of 5, and there was an association between slower growth and decreased cognitive ability.
RESUMO
Two inhibitors of Taq DNA polymerase were isolated from the marine red alga Symphyocladia latiuscula. The inhibitors were purified by methanol extraction, molecular fractionation below 3000 MW and reverse-phase HPLC. The purified compound SL-1 containing three bromines was identified as 2,3,6-tribromo-4,5-dihydroxybenzyl alcohol (C7H5Br3O3: MW374) by NMR and MS analyses. The purified compound SL-2 was identified as 2,3, 6-tribromo-4,5-dihydroxybenzyl methyl ether(C8H7Br3O3: MW388). In a 25-microl reaction mixture containing 1.5 units of Taq DNA polymerase, the enzyme was completely inhibited by 0.5 microg SL-1 or 5 microg SL-2.
Assuntos
Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Hidrocarbonetos Bromados/isolamento & purificação , Hidrocarbonetos Bromados/farmacologia , Rodófitas/química , Taq Polimerase/antagonistas & inibidores , Sequência de Bases , Cromatografia Líquida de Alta Pressão , Eletroforese em Gel de Ágar , Inibidores Enzimáticos/química , Éteres , Hidrocarbonetos Bromados/química , Metanol/química , Peso Molecular , Reação em Cadeia da Polimerase , Análise EspectralRESUMO
The effect of utilizing Ex12 helper phage, a mutant M13K07 helper having two amber codons at the gIII (gIII-amber), in combination with Escherichia coli host strains belonging to the supE genotype on improving the phage display of antibody fragments was investigated. Because of an inefficient read-through of the UAG codons, Ex12 helper phage produced approximately 10% of the intracellular wt pIII in the supE host cells compared to M13K07. The phage progenies rescued from the supE XL-1 Blue MRF' strain carrying the recombinant phagemid, pCMTG-SP112, by Ex12 helper phage displayed both antibody-DeltapIII fusion and wt pIII at a ratio of 1:1.5, and achieved a 50-fold greater display of the antibody-DeltapIII compared to those obtained by a conventional phage rescue using M13K07. Additionally observed were a 100-fold increase in antigen-binding functionality and a drastic improvement on antigen-specific panning efficiency by the phage progenies. Our approach permits the display of at least one antibody fragment as well as more than one copy of wt pIII on the surface of recombinant phages, and this would make the phagemid-based phage display technology more practical and reliable.
Assuntos
Bacteriófago M13/genética , Genes Supressores , Vírus Auxiliares/genética , Fragmentos de Imunoglobulinas/genética , Biblioteca de Peptídeos , Sequência de Aminoácidos , Afinidade de Anticorpos/genética , Especificidade de Anticorpos/genética , Dados de Sequência MolecularRESUMO
Selenophosphate synthetase catalyzes the synthesis of selenophosphate which is a selenium donor for Sec biosynthesis. In Drosophila melanogaster, there are two types of selenophosphate synthetases designated dSPS1 and dSPS2, where dSPS2 is a selenoprotein. The mechanism of gene expression of dSPS2 as well as other selenoproteins in Drosophila has not been elucidated. Herein, we report an essential regulator system that regulates the transcription of the dSPS2 gene (dsps2). Through deletion/substitution mutagenesis, the downstream DNA replication-related element (DRE) located at +71 has been identified as an essential element for dsps2 promoter activity. Furthermore, double-stranded RNA interference (dsRNAi) experiments were performed to ablate transcription factors such as TBP, TRF1, TRF2 and DREF in Schneider cells. The dsRNAi experiments showed that dsps2 promoter activities in DREF- and TRF2-depleted cells were significantly decreased by 90% and 50%, respectively. However, the depletion of TBP or TRF1 did not affect the expression level of dsps2 even though there is a putative TATA box at -20. These results strongly suggest that the DRE/DREF system controls the basal level of transcription of dsps2 by interacting with TRF2.
Assuntos
Proteínas de Drosophila/genética , Drosophila/genética , Fosfotransferases/genética , Elementos de Resposta , Ativação Transcricional , Região 5'-Flanqueadora , Animais , Sequência de Bases , Sítios de Ligação , Clonagem Molecular , Replicação do DNA , Drosophila/enzimologia , Indução Enzimática , Genes de Insetos , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Interferência de RNA , Fatores de Transcrição/metabolismo , Fatores de Transcrição/fisiologia , Sítio de Iniciação de TranscriçãoRESUMO
OBJECTIVES: An extract of Artemisia asiatica was reported to possess antioxidative and cytoprotective actions in various experiments. Ischemia-reperfusion injury remains a major problem in kidney transplant, and the inflammatory response to ischemia-reperfusion injury exacerbates the resultant renal injury. In the present study, we investigated whether an extract of Artemisia asiatica exhibits renoprotective effects against ischemia-reperfusion-induced acute kidney injury in mice. MATERIALS AND METHODS: Renal ischemia-reperfusion injury was induced in male C57BL/6 mice by bilateral renal pedicle occlusion for 30 minutes followed by reperfusion for 48 hours. An extract of Artemisia asiatica (100 mg/kg oral) was administered 4 days before ischemia-reperfusion injury. Sham operation and phosphate-buffered saline were used as controls. Blood and renal tissues were evaluated at 48 hours after ischemiareperfusion injury. RESULTS: Treatment with an extract of Artemisia asiatica significantly decreased blood urea nitrogen, serum creatinine levels, and kidney tubular injury (P ≤ .05). Western blot showed that an extract of Artemisia asiatica significantly increased the level of heme oxygenase-1 and B-cell lymphoma 2 at 48 hours after ischemia-reperfusion injury and attenuated the level of inducible nitric oxide synthase. CONCLUSIONS: An extract of Artemisia asiatica improves acute renal ischemia-reperfusion injury by reducing inflammation and apoptosis. These findings suggest that an extract of Artemisia asiatica is a potential therapeutic agent against acute ischemia-induced renal damage.
Assuntos
Injúria Renal Aguda/prevenção & controle , Artemisia , Rim/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Animais , Biomarcadores/sangue , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Citoproteção , Modelos Animais de Doenças , Heme Oxigenase-1/metabolismo , Rim/irrigação sanguínea , Rim/metabolismo , Rim/patologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/metabolismo , Fitoterapia , Plantas Medicinais , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Fatores de TempoRESUMO
A semi-synthetic human scFv phage display library by randomizing amino acid residues at CDR3H was constructed using pIGT3 phagemid vector. Recombinant phages were rescued by super-infecting the JS5 E. coli library stock with Ex-phage, the mutant M13KO7 helper phage containing amber mutations at gIII. The library was composed of 2 x 10(8) independent clones, and selected for the specific binders against malonyl-CoA decarboxylase (MCD) by panning. Five soluble scFv clones specific for MCD were finally identified and classified into two groups based on the difference in their binding pattern to MCD. Two clones (M4 and M8) showed good binding reactivity to MCD in ELISA but not in Western blot, whereas, the rest three clones (M23, M28 and M41) reacted to the antigen in Western blot but not in ELISA implying they bound to somewhat different epitopes on MCD. DNA sequencing analysis of M4, M8, M23 and M28 showed that VH of all clones were belonged to VH3 subgroup. On the other hand, M4 and M8 utilized VLkappa subgroup I, and M23 and M28 used VLkappa subgroup IV, suggesting that difference in binding pattern between M4/M8 and M23/M28 against MCD might come from the different VL gene utilization. In conclusion, human monoclonal scFv antibodies specific for MCD were successfully isolated and we demonstrated that distinct populations of recombinant antibodies specific to the target antigen could be isolated by Ex-phage system.
Assuntos
Especificidade de Anticorpos , Carboxiliases/imunologia , Região Variável de Imunoglobulina/genética , Região Variável de Imunoglobulina/imunologia , Biblioteca de Peptídeos , Sequência de Aminoácidos , Animais , Bacteriófagos/genética , Bacteriófagos/imunologia , Sequência de Bases , Western Blotting , Cromatografia de Afinidade , Ensaio de Imunoadsorção Enzimática , Humanos , Dados de Sequência Molecular , Ratos , Alinhamento de Sequência , SolubilidadeRESUMO
BACKGROUND AND PURPOSE: The vertebral artery (VA) is important for the development of the transverse foramen (TF). Most studies of these structures have focused on anatomical anomalies. Therefore, we investigated quantitatively the association between the relative sizes of the TF and VA. METHODS: We recruited a consecutive series of subjects who underwent CT angiography to estimate the relative sizes of the VA and TF in axial source images. Two neurologists independently reviewed the axial CT images of 208 patients who had no history of transient ischemic attack or stroke. Averaged areas of the VA and TF were defined by the sum of the areas at each level from C3 to C6, divided by 4. Correlation analyses were adjusted for age, sex, and vascular risk factors. RESULTS: The mean age of the subjects was 53 years. The interobserver and intraobserver reliabilities of TF size were good. There was a linear relationship between the sizes of the VA and TF on each side (right side: r(2)=0.58, p<0.001; left side: r(2)=0.62, p<0.001). The area of the VA was significantly associated with that of the TF after adjusting for vascular risk factors. CONCLUSIONS: The size of the VA is strongly and linearly correlated with the size of the TF. These findings suggest that measurement of the TF and VA with CT angiography is a reliable method for evaluating VA diseases, and may provide new insight into the differentiation between VA hypoplasia and atherosclerosis of the VA.
RESUMO
BACKGROUND AND PURPOSE: It was recently reported that the prevalence of poststroke memory dysfunction might be higher than previously thought. Stroke may exist concomitantly with underlying Alzheimer's disease (AD), and so we determined whether post-stroke memory dysfunction indicates manifestation of underlying subclinical AD. METHODS: Of 1201 patients in a prospective cognitive assessment database, we enrolled subjects with poststroke amnestic vascular cognitive impairment-no dementia (aVCIND; n=48), poststroke nonamnestic vascular cognitive impairment-no dementia (naVCIND; n=50), and nonstroke amnestic mild cognitive impairment (aMCI; n=65). All subjects had cognitive deficits, but did not meet the criteria for dementia. A standardized neuropsychological test battery and magnetic resonance imaging were performed at least 90 days after the index stroke (mean, 473 days). Visual assessment of medial temporal atrophy (MTA) was used as a measure of underlying AD pathology. RESULTS: The MTA score was significantly lower in the naVCIND group (0.64±0.85, mean±SD) than in the aVCIND (1.10±1.08) and aMCI (1.45±1.13; p<0.01) groups. Multivariable ordinal logistic regression analysis revealed that compared with naVCIND, aVCIND [odds ratio (OR)=2.69; 95% confidence interval (CI)=1.21-5.99] and aMCI (OR=5.20; 95% CI=2.41-11.23) were significantly associated with increasing severity of MTA. CONCLUSIONS: Our findings show that compared with poststroke naVCIND, the odds of having more-severe MTA were increased for poststroke aVCIND and nonstroke aMCI.