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1.
J Neurogenet ; 36(1): 11-20, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35098860

RESUMO

Alzheimer's disease (AD) is the leading cause of dementia globally, but effective treatment is lacking. We aimed to explore lncRNA XIST role in AD and the mechanisms involved in the effect of changes in lncRNA XIST on the expression of Aß-degrading enzymes. The mouse model of AD and the cell model induced by Aß were established. LncRNA XIST, IDE, NEP, Plasmin, ACE, EZH2 expressions and distribution of XIST in the nucleus and cytoplasm were detected by qRT-PCR. Inflammatory cytokines IL-6, IL-1ß, TNFα, IL-8, and Aß42 levels were detected by ELISA. TUNEL was used to measure brain tissue damage. Cell proliferation was detected by CCK-8 assay. Flow cytometry detected cell apoptosis. RIP validated the combination of XIST and EZH2. ChIP verified that XIST recruits EZH2 to mediate enrichment of HEK27me3 in the NEP promoter region. The protein expression in brain tissues and cells was detected by Western blot. The expression of lncRNA XIST was increased in AD mice and cell models. Inflammation and injury of nerve cells occurred in AD mice and cell models. The knockdown of lncRNA XIST alleviated Aß-induced neuronal inflammation and damage. LncRNA XIST affected the expression of Aß-degrading enzyme NEP, and lncRNA XIST was negatively correlated with NEP expression in AD mice. LncRNA XIST regulated NEP expression partly through epigenetic regulation by binding with EZH2. LncRNA XIST mediated neuronal inflammation and injury through epigenetic regulation of NEP. Overall, our study found that lncRNA XIST induced Aß accumulation and neuroinflammation by the epigenetic repression of NEP in AD.


Assuntos
Doença de Alzheimer , MicroRNAs , RNA Longo não Codificante , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Animais , Epigênese Genética , Repressão Epigenética , Camundongos , Neprilisina/genética , Neprilisina/metabolismo , Doenças Neuroinflamatórias , RNA Longo não Codificante/genética
2.
BMC Pediatr ; 19(1): 495, 2019 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-31830932

RESUMO

BACKGROUND: This study aims to investigate the application value of three-dimensional arterial spin labeling (3DASL) in investigating cerebral blood flow dynamics in full-term neonates. METHODS: A total of 60 full-term neonates without known intracranial pathology were recruited for 3DASL examination. These neonates were divided into three groups: 1-3 day group, 4-7 day group, and 8-15 day group. On the cerebral blood flow (CBF) images, regions of interest (ROI) were selected from the frontal white matter, parietal white matter, basal ganglia, corona radiata, thalamus and brainstem, and the CBF values of each ROI were recorded. The CBF values of ROIs at bilaterally symmetric locations, the values of each ROI between males and females, and the values of each ROI among these three different age groups were compared. RESULTS: The difference in CBF values of the frontal white matter, parietal white matter, basal ganglia, corona radiata and thalamus at the bilateral symmetric positions were not statistically significant. There was no statistical difference in the CBF values of each brain region between the male and female groups. The CBF values at the basal ganglia region, corona radiata and parietal white matter were higher in the 8-15 day group, when compared to the 1-3 day and 4-7 day groups (P < 0.05). The CBF value at the basal ganglia region was higher in the 4-7 day group, when compared to the 1-3 day group (P < 0.05). The CBF value at the frontal white matter was lower in the 4-7 day group, when compared to the 1-3 day and 8-15 day group (P < 0.05). The CBF value at the brainstem was higher in the 4-7 day group, when compared to the 1-3 day and 8-15 day groups (P < 0.05). CONCLUSION: The 3DASL can quantitatively measure CBF, and be used to evaluate cerebral hemodynamics in neonates. The basal ganglia region and corona radiata CBF increases with the increase in neonatal diurnal age.


Assuntos
Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular , Imageamento Tridimensional , Imagem de Perfusão , Fluxo Sanguíneo Regional , Feminino , Humanos , Recém-Nascido , Masculino , Valores de Referência , Marcadores de Spin , Nascimento a Termo
3.
Cell Physiol Biochem ; 47(1): 97-106, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29763886

RESUMO

BACKGROUND/AIMS: Unlike other organs, which only have one set of capillary network, the renal microvasculature consists of two sets of capillary network series connected by efferent arterioles. Angiotensin II constricts the efferent glomerular artery. Hence, renal tumor blood flow (BF) distribution may be different from tumors in other organs. This study aims to investigate the effects of angiotensin II on the hemodynamics of intrarenal VX2 tumors using perfusion computed tomography(CT). METHODS: Twenty-four male New Zealand white rabbits were randomly divided into three groups: groups A (blank controls), group B (negative controls), and group C (angiotensin II-treated animals). Group B and C were established to the model of intrarenal VX2 tumors. Furthermore, perfusion CT of the kidney was performed in each group. Prior to perfusion CT scan in group C, the mean arterial blood was elevated to 150-160 mmHg by angiotensin II. The BF, blood volume (BV), mean transit time (MTT), capillary permeability-surface area product (PS), and relative permeability-surface area product (RPS) of tumors and renal tissues were calculated. RESULTS: Compared with normal renal cortex tissues in group A, the BF, BV and PS values of tumors in group B were significantly lower, MTT was prolonged and RPS increased. Compared with group B, only the RPS of these tumors increased from 83.23 ± 29.17% to 120.94 ± 31.84% by angiotensin II infusion. Angiotensin II significantly increased the RPS value of the renal cortex distant from the tumor (CDT) and the right renal cortex (RRC). CONCLUSIONS: Perfusion CT can accurately observe the influence of angiotensin II on normal and tumor BF in kidneys. This clarifies the effect of angiotensin II on intrarenal tumor hemodynamics.


Assuntos
Angiotensina II/farmacologia , Hemodinâmica/efeitos dos fármacos , Neoplasias Renais/irrigação sanguínea , Rim/irrigação sanguínea , Tomografia Computadorizada por Raios X/métodos , Vasoconstritores/farmacologia , Animais , Rim/diagnóstico por imagem , Rim/efeitos dos fármacos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/tratamento farmacológico , Masculino , Neovascularização Patológica/diagnóstico por imagem , Neovascularização Patológica/tratamento farmacológico , Perfusão/métodos , Coelhos
4.
Jpn J Radiol ; 36(5): 345-350, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29616398

RESUMO

PURPOSE: To investigate the effect of automatic spectral imaging protocol selection (ASIS) and adaptive statistical iterative reconstruction (ASIR) technology in reducing radiation and contrast dosage. METHODS: Sixty-four patients were randomly divided into two groups for abdominal computed tomography (CT): the experiment group with ASIS plus 50% ASIR and the control with 120 kVp voltage. RESULTS: The CT dose-index volume decreased by 23.68 and 23.57% and the dose-length product dropped by 25.59 and 18.45% in the arterial and portal venous phases, respectively, in the experiment than control group. The contrast dose was reduced by 16.86% in the experiment group. In the 55 keV + 50% ASIR group, the arterial contrast-to-noise ratio and scores were significantly (P < 0.05) higher than in the control group in the arterial phase while the portal contrast-to-noise ratio and scores were not significantly different between the two groups (P > 0.05). CONCLUSION: The ASIS technique plus 50% ASIR can enhance image quality of the abdominal structures while decreasing the radiation and contrast dosage compared with the conventional scan mode.


Assuntos
Abdome/irrigação sanguínea , Abdome/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Meios de Contraste/administração & dosagem , Processamento de Imagem Assistida por Computador/métodos , Doses de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intensificação de Imagem Radiográfica/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos
5.
Eur J Radiol ; 89: 47-53, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28267548

RESUMO

OBJECTIVE: To investigate the effect of the optimal monochromatic spectral computed tomography (CT) plus adaptive statistical iterative reconstruction on the improvement of the image quality of the superior mesenteric artery and vein. MATERIALS AND METHODS: The gemstone spectral CT angiographic data of 25 patients were reconstructed in the following three groups: 70KeV, the optimal monochromatic imaging, and the optimal monochromatic plus 40%iterative reconstruction mode. The CT value, image noises (IN), background CT value and noises, contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR) and image scores of the vessels and surrounding tissues were analyzed. RESULTS: In the 70KeV, the optimal monochromatic and the optimal monochromatic images plus 40% iterative reconstruction group, the mean scores of image quality were 3.86, 4.24 and 4.25 for the superior mesenteric artery and 3.46, 3.78 and 3.81 for the superior mesenteric vein, respectively. The image quality scores for the optimal monochromatic and the optimal monochromatic plus 40% iterative reconstruction groups were significantly greater than for the 70KeV group (P<0.05). The vascular CT value, image noise, background noise, CNR and SNR were significantly (P<0.001) greater in the optimal monochromatic and the optimal monochromatic images plus 40% iterative reconstruction group than in the 70KeV group. The optimal monochromatic plus 40% iterative reconstruction group had significantly (P<0.05) lower image and background noise but higher CNR and SNR than the other two groups. CONCLUSION: The optimal monochromatic imaging combined with 40% iterative reconstruction using low-contrast agent dosage and low injection rate can significantly improve the image quality of the superior mesenteric artery and vein.


Assuntos
Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Artéria Mesentérica Superior/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intensificação de Imagem Radiográfica/métodos , Razão Sinal-Ruído
6.
J Nephrol ; 30(3): 397-402, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27068829

RESUMO

AIM: To investigate the application of the new modified Chronic Kidney Disease Epidemiology Collaboration (mCKD-EPI) equation developed by Liu for the measurement of glomerular filtration rate (GFR) in Chinese patients with chronic kidney disease (CKD) and to evaluate whether this modified form is more accurate than the original one in clinical practice. METHODS: GFR was determined simultaneously by 3 methods: (a) 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA) dual plasma sample clearance method (mGFR), which was used as the reference standard; (b) CKD-EPI equation (eGFRckdepi); (c) modified CKD-EPI equation (eGFRmodified). Concordance correlation and Passing-Bablok regression were used to compare the validity of eGFRckdepi and eGFRmodified. Bias, precision and accuracy were compared to identify which equation showed the better performance in determining GFR. RESULTS: A total of 170 patients were enrolled. Both eGFRckdepi and eGFRmodified correlated well with mGFR (concordance correlation coefficient 0.90 and 0.74, respectively) and the Passing-Bablok regression equation of eGFRckdepi and eGFRmodified against mGFR was mGFR = 0.37 + 1.04 eGFRckdepi and -49.25 + 1.74 eGFRmodified, respectively. In terms of bias, precision and 30 % accuracy, eGFRmodified showed a worse performance compared to eGFRckdepi, in the whole cohort. CONCLUSIONS: The new modified CKD-EPI equation cannot replace the original CKD-EPI equation in determining GFR in Chinese patients with CKD.


Assuntos
Taxa de Filtração Glomerular , Rim/fisiopatologia , Modelos Biológicos , Insuficiência Renal Crônica/diagnóstico , Adulto , Idoso , Povo Asiático , Biomarcadores/sangue , China/epidemiologia , Creatinina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos/administração & dosagem , Insuficiência Renal Crônica/etnologia , Insuficiência Renal Crônica/fisiopatologia , Reprodutibilidade dos Testes , Pentetato de Tecnécio Tc 99m/administração & dosagem
7.
Exp Ther Med ; 12(2): 783-791, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27446276

RESUMO

The diagnostic value of contrast-enhanced ultrasound (CEUS) or real-time elastography (RTE) alone, as well as a combination of CEUS and RTE, in distinguishing benign from malignant thyroid nodules was investigated. Between August 2012 and June 2014, a total of 97 consecutive patients (50 male and 47 female patients; mean age, 48.6±12.4; age range, 27-70 years) with thyroid nodules referred for surgical treatment were examined by CEUS and RTE. The final diagnosis was obtained based on histological findings. Image analysis of the CEUS and RTE scans was performed. Considering the postoperative pathological results as the golden standard, a receiver operating characteristic (ROC) curve was constructed. Subsequently, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of CEUS alone, RTE alone and CEUS + RTE combination were calculated. Pathological examination showed 66 papillary carcinomas and 43 benign lesions, including 21 adenomas and 22 nodular goiters. The sensitivity, specificity, PPV, NPV and accuracy of CEUS were 81.82, 90.70, 93.10, 90.70 and 85.32%, respectively. In the case of RTE, the sensitivity, specificity, PPV, NPV and accuracy were 80.30, 88.37, 91.38, 88.37 and 83.49%, respectively. Furthermore, the combination of CEUS + RTE had a sensitivity of 95.45%, specificity of 95.35%, PPV of 96.92%, NPV of 95.35% and accuracy of 95.41%. Therefore, the CEUS + RTE combination showed a significantly higher sensitivity and specificity compared with CEUS or RTE alone (all P<0.05). Based on ROC analysis, the area under the curve (AUC) for CEUS, RTE and CEUS + RTE combination was 0.883, 0.863 and 0.959, respectively. The AUC of RTE alone was significantly lower compared with that of the CEUS + RTE combination. In conclusion, our results demonstrate that CEUS + RTE combination significantly increases the diagnostic performance for differential diagnosis of malignant and benign thyroid nodules compared with CEUS or RTE alone.

8.
Biomarkers ; 20(6-7): 474-80, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26616148

RESUMO

BACKGROUND: Adiponectin (ADP) polymorphisms associated with diabetes mellitus in several populations. However, no previous studies have investigated its association with diabetic peripheral neuropathy (DPN). Our study examined the association between ADP-linked SNPs and DPN susceptibility. METHODS: We randomly recruited 160 diabetes mellitus (DM) patients and 80 healthy individuals. RESULTS: The C allele of rs3821799 increased DPN susceptibility. In normal individuals, GG of rs3774261 carriers had 7.1 times higher DPN susceptibility than AA carriers. The haplotype analyzes indicated CGG might increase DPN susceptibility. CONCLUSION: Our study demonstrated that ADP gene polymorphisms are associated with the susceptibility to DPN.


Assuntos
Adiponectina/genética , Neuropatias Diabéticas/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Alelos , Sequência de Bases , Glicemia/metabolismo , Colesterol/sangue , Neuropatias Diabéticas/sangue , Feminino , Frequência do Gene , Genótipo , Hemoglobinas Glicadas/metabolismo , Haplótipos , Humanos , Desequilíbrio de Ligação , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Razão de Chances , Análise de Sequência de DNA/métodos , Tireoglobulina/sangue
9.
J Diabetes Complications ; 29(7): 887-92, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26144281

RESUMO

OBJECTIVE: In this study, we examined the association between two adiponectin (ADPN) gene polymorphisms, +45T/G and +276G/T, and susceptibility to diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 180 T2DM patients were enrolled in this study and assigned to two groups: DPN group (n=90) and non-DPN (NDPN) group (n=90). In addition, 90 healthy subjects were chosen as healthy normal control (NC). The plasma level of ADPN was quantified by ELISA method and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for genotype analysis of the two ADPN polymorphisms, +45T/G (rs2241766) and +276G/T (rs1501299), in all the study subjects. Statistical analysis of data was performed with SPSS version 20.0 software. RESULTS: Serum levels of ADPN were markedly reduced in the DPN group compared to NDPN and NC groups (all P<0.05). The frequencies of TT, TG and GG genotypes and the T and G alleles of T45G and G276T polymorphisms in DPN group were significantly different than the NDPN group (all P<0.05). Notably, T45G and G276T polymorphisms were associated with significantly reduced plasma levels of ADPN in DPN and NDPN groups, compared to the NC group (P<0.001). Significant difference in ADPN plasma levels were also observed between TT, TG and GG genotypes of T45G and G276T polymorphisms. Our results indicate that the T allele in +45T/G and +276G/T polymorphisms is correlated with an elevated risk of DPN in T2DM patients. Haplotype analysis showed that GG and GT haplotypes showed a negative relationship with DPN, while TG haplotype positively correlated with risk of DPN in T2DM patients (all P<0.05). CONCLUSION: Our results show that T45G and G276T polymorphisms of ADPN are associated with a significantly elevated risk of DPN in T2DM patients, likely by down-regulating ADPN serum level.


Assuntos
Adiponectina/genética , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/genética , Predisposição Genética para Doença/epidemiologia , Alelos , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/terapia , Neuropatias Diabéticas/epidemiologia , Feminino , Frequência do Gene , Haplótipos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prognóstico , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença
10.
PLoS One ; 9(10): e108883, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25272033

RESUMO

PURPOSE: To investigate correlations between altered spontaneous brain activity, diabetic vascular disease, and cognitive function for patients with type 2 diabetes mellitus (T2DM) using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Rs-fMRI was performed for T2DM patients (n = 26) and age-, gender-, and education-matched non-diabetic control subjects (n = 26). Amplitude of low frequency fluctuations (ALFF) were computed from fMRI signals to measure spontaneous neuronal activity. Differences in the ALFF patterns between patients and controls, as well as their correlations with clinical variables, were evaluated. RESULTS: Compared with healthy controls, T2DM patients exhibited significantly decreased ALFF values mainly in the frontal and parietal lobes, the bilateral thalumi, the posterior lobe of the cerebellum, and increased ALFF values mainly in the visual cortices. Furthermore, lower ALFF values in the left subcallosal gyrus correlated with lower ankle-brachial index values (r = 0.481, p = 0.020), while lower ALFF values in the bilateral medial prefrontal gyri correlated with higher urinary albumin-creatinine ratio (r =  -0.418, p = 0.047). In addition, most of the regions with increased ALFF values in the visual cortices were found to negatively correlate with MoCA scores. CONCLUSIONS: These results confirm that ALFF are altered in many brain regions in T2DM patients, and this is associated with the presence of diabetic vascular disease and poor cognitive performance. These findings may provide additional insight into the neurophysiological mechanisms that mediate T2DM-related cognitive dysfunction, and may also serve as a reference for future research.


Assuntos
Encéfalo/fisiopatologia , Cognição/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/fisiopatologia , Adulto , Idoso , Encéfalo/patologia , Mapeamento Encefálico , Diabetes Mellitus Tipo 2/patologia , Angiopatias Diabéticas/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Descanso/fisiologia
11.
Neurol Sci ; 32(3): 433-41, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21409508

RESUMO

In the present study, we evaluated the neuroprotection time window for nerve growth factor (NGF) after ischemia/reperfusion brain injury in rabbits as related to this anti-apoptosis mechanism. Male New Zealand rabbits were subjected to 2 h of middle cerebral artery occlusion (MCAO), followed by 70 h of reperfusion. NGF was administered after injury to evaluate the time window. Neurological deficits, infarct volume, neural cell apoptosis and expressions of caspase-3 and Bcl-2 were measured. Compared to saline-treated control, NGF treatment at 2, 3 and 5 h after MCAO significantly reduced infarct volume, neural cell apoptosis and expression of caspase-3 (P < 0.01), up-regulated the expression of Bcl-2 and improved functional recovery (P < 0.01). However, treatment at latter time points did not produce significant neuroprotection. Neuroprotection treatment with NGF provides an extended time window of up to 5 h after ischemia/reperfusion brain injury, in part by attenuating the apoptosis.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Fator de Crescimento Neural/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Animais , Isquemia Encefálica/patologia , Modelos Animais de Doenças , Esquema de Medicação , Injeções Intraventriculares , Masculino , Fator de Crescimento Neural/fisiologia , Fármacos Neuroprotetores/farmacologia , Coelhos , Traumatismo por Reperfusão/patologia , Fatores de Tempo
12.
J Invest Surg ; 23(3): 149-55, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20590386

RESUMO

We evaluated the effects of intranasal vascular endothelial growth factor VEGF on neurological function and angiogenesis in ischemic boundary following cerebral ischemia. Sprague-Dawley rats were randomized into sham operation group (n = 9), VEGF group (n = 18), and control group (n = 18). The VEGF and control rats were intranasally administered (IN) with VEGF or saline, starting three days after middle cerebral artery occlusion (MCAO) and daily. Neurological scores were obtained at 1, 7, and 14 days after MCAO. Rats were sacrificed at 14 days, the von Willebrand factor (vWF) immunoreactive, BrdU(+)/vWF(+) cells, and microvessels were evaluated respectively. Compared to the control rats, intranasal administration of VEGF improved behavioral recovery, and increased the number of vWF(+), BrdU(+)/vWF(+) cells, and FITC-dextran perfused microvessels in ischemic boundary (p < .01). Our data suggest that intranasal administration of VEGF may induce angiogenesis in ischemic boundary and improve behavioral recovery following cerebral ischemia in rats, which may provide a powerful strategy for stroke.


Assuntos
Neovascularização Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Acidente Vascular Cerebral/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/farmacologia , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Administração Intranasal , Animais , Comportamento Animal/fisiologia , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/fisiopatologia , Masculino , Microvasos/fisiologia , Modelos Animais , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/administração & dosagem
13.
Neurosci Lett ; 461(3): 212-6, 2009 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-19559076

RESUMO

The aim of the present study was to assess the dose-effectiveness of intranasal (IN) vascular endothelial growth factor (VEGF)in the treatment of experimental stroke. Sprague-Dawley rats were randomized into four groups as IN low (100 microg/ml), IN middle (200 microg/ml) and IN high (500 microg/ml) VEGF-treated group, and IN saline-treated group (n=12), given recombinant human VEGF 165 or saline intranasally. Focal cerebral ischemia was induced by transient (90 min) middle cerebral artery occlusion (MCAO) method. Behavioral neurological deficits were assessed 1, 7 and 14 d after the onset of MCAO. Rats were sacrificed at 14 d, the brain sections were stained and an image analysis system was used to calculate the infarct volume. Microvessels were labeled by FITC-dextran and the segment lengths, diameters and number of microvessels were measured by Image Pro-Plus Version 6.0 software. Fourteen days post MCAO, infarct volume significantly reduced (P<0.01) in rats which received the middle dose of IN VEGF when compared to IN saline. And middle dose of VEGF significantly improved behavioral recovery (P<0.01). No significant difference in the behavioral recovery and infarct volume was observed between the saline-treated group and the low or high VEGF-treated groups (P>0.05). Compared to IN saline, middle and high doses of VEGF significantly increased the segment length, diameter and number of microvessels (P<0.01). No significant difference in the segment length, diameter and number of microvessels was observed between the IN saline-treated group and the low VEGF-treated group (P>0.05). The middle dose of IN VEGF was most effective on reducing infarct volume, improving behavioral recovery and enhancing angiogenesis in stroke brain, which can be used in the following treatments to further evaluate the effect of VEGF.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Administração Intranasal , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/irrigação sanguínea , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Isquemia Encefálica/complicações , Isquemia Encefálica/patologia , Relação Dose-Resposta a Droga , Humanos , Infarto da Artéria Cerebral Média/complicações , Masculino , Microvasos/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologia , Fator A de Crescimento do Endotélio Vascular/administração & dosagem
14.
Neurol Sci ; 30(3): 227-32, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19387543

RESUMO

Caspase-12 has been localized to endoplasmic reticulum (ER) and showed to involve ER stress-induced apoptosis. In the present work we investigated the temporospatial alterations of caspase-12 immunoreactivity in the penumbra following cerebral ischemia/reperfusion in rabbit. Transient cerebral ischemia was produced by intraluminal occlusion of the middle cerebral artery for 2 h followed by 1 h, 6 h, 1 day, 3 days, 7 days and 14 days of reperfusion. Caspase-12 immunohistochemistry was first increased in the penumbra 1 h after reperfusion, with a peak at day 1 to day 3, and then gradually decreased to basal level at day 14. The number of TUNEL-positive cells and ultrastructural observation of brain sections in the penumbra showed a similar change at the same time points. ER mediated by caspase-12 participated in apoptosis induced by cerebral ischemia/reperfusion injury, which may provide a new area for therapeutic intervention to ameliorate outcomes following cerebral ischemia.


Assuntos
Apoptose/fisiologia , Caspase 12/metabolismo , Cérebro/enzimologia , Retículo Endoplasmático/enzimologia , Traumatismo por Reperfusão/enzimologia , Animais , Cérebro/patologia , Cérebro/ultraestrutura , Seguimentos , Imuno-Histoquímica , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/enzimologia , Infarto da Artéria Cerebral Média/patologia , Masculino , Coelhos , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Fatores de Tempo
15.
Neurol Res ; 31(10): 1092-6, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19309539

RESUMO

OBJECTIVE: Occluding the middle cerebral artery of small animals with an intraluminal filament to build a stroke model has gained increasing acceptance. In light of the growing demand for magnetic resonance imaging (MRI) studies using the clinical MRI scanner, large animal models can be superior to small animal models. In this work, we developed a modified rabbit model of stroke, which was assessed using clinical MRI scanner and compared with a most commonly silicone-coated filament model. METHODS: We presented a focal cerebral ischemia in rabbits. The key feature of this modified method is the use of a guide wire as a 'nylon suture'. At 3 days after ischemia, the percentage of brain infarct volume, neurobehavioral score, intracranial hemorrhagic incidence and dynamic changes of T(2) and apparent diffusion coefficient values were assessed respectively and compared between the focal cerebral models. RESULTS: Wire-induced models had more severe brain infarct size with less dispersion (32.7 +/- 6.5%, coefficient of variation=0.20) than that with filament models (25.4 +/- 8.9%, coefficient of variation=0.31; p<0.05). There were more significant MRI changes in the early stage, higher rate of technique success (wire, 20/20; filament, 17/20) and less intracranial hemorrhage (wire, 0/20; filament, 3/20) in wire-induced models than in filament-induced rabbits (p<0.05). CONCLUSION: Our data suggest that wire-induced method can provide a useful tool for the earlier research of ischemia.


Assuntos
Encéfalo/patologia , Infarto da Artéria Cerebral Média/patologia , Acidente Vascular Cerebral/patologia , Análise de Variância , Animais , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/fisiopatologia , Imageamento por Ressonância Magnética , Coelhos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia
16.
J Invest Surg ; 22(1): 29-34, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19191155

RESUMO

Researchers suggest that endoplasmic reticulum (ER) stress cause apoptosis after ischemia. Caspase-12 has been localized to the ER and is a signal for apoptosis. We sought to clarify the role of caspase-12 in the vascular endothelial growth factor (VEGF) induced neuroprotective effect. Transient focal cerebral ischemia was produced by occluding left middle cerebral artery in rabbit. The expressions of caspase-12 and caspase-3 were detected by immunohistochemistry. Neuronal apoptosis was detected by TUNEL staining. We confirmed that the number of apoptotic cells and the expressions of caspase-12 and caspase-3 significantly increased during reperfusion. VEGF inhibited the cell apoptosis and the expressions of caspase-12 and caspase-3. These results suggest that VEGF may protect neurons from apoptosis by inhibiting ER stress pathway.


Assuntos
Apoptose , Caspase 12/metabolismo , Retículo Endoplasmático/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Caspase 3/metabolismo , Cérebro/patologia , Citometria de Fluxo , Marcação In Situ das Extremidades Cortadas , Infarto da Artéria Cerebral Média/patologia , Masculino , Coelhos , Reperfusão , Traumatismo por Reperfusão/patologia , Estresse Fisiológico
17.
Neurosci Lett ; 449(2): 108-11, 2009 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-18996442

RESUMO

The aim of the present study was to assess the potential of delivering VEGF directly into the central nervous system (CNS) following intranasal administration. Adult Sprague-Dawley rats were randomized into two groups, given [(125)I]-VEGF intranasally or intravenously. VEGF was intranasally administered in both nares alternately, the single dose is 10 microl with time interval of 2 min for about 18.5 min. The intravenous (IV) group was treated with 100 microl [(125)I]-VEGF intravenously. Thirty minutes after administration, rats were killed following blood sample collections, then the brains were removed, and olfactory bulb, striatum corpora, cortex, thalamus, pons, cerebella, medulla, hippocampus, cervical cord and other tissues were collected, weighted, under auto gamma counting and autoradiography analysis. Cisternal sampling of cerebrospinal fluid (CSF) was performed in an additional group of animals. Both gamma counting and high resolution phosphor imaging of tissue sections showed that intranasal administration of [(125)I]-VEGF resulted in substantial delivery throughout the CNS. The highest CNS tissue concentration following IN delivery was found in the trigeminal nerve, followed by the optic nerve, olfactory bulbs, olfactory tubercle, striatum, medulla, frontal cortex, midbrain, pons, appendix cerebri, thalamus, hippocampus, cerebellum. Intranasal administration of [(125)I]-VEGF also targeted the deep cervical lymph nodes. CSF did not contain [(125)I]-VEGF following intranasal administration. Intravenous [(125)I]-VEGF resulted in blood and peripheral tissue exposure higher concentrations than that intranasal administration, but CNS concentrations were significantly lower. The results suggest intranasally delivered VEGF can bypass the blood-brain barrier via olfactory- and trigeminal-associated extracellular pathways to directly entry into the CNS. Intranasal administration of VEGF may provide an effective way for the treatments of CNS diseases.


Assuntos
Encéfalo/metabolismo , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/farmacocinética , Administração Intranasal , Vias Aferentes/anatomia & histologia , Vias Aferentes/efeitos dos fármacos , Vias Aferentes/metabolismo , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Encéfalo/anatomia & histologia , Encéfalo/efeitos dos fármacos , Radioisótopos do Iodo/farmacocinética , Cavidade Nasal/efeitos dos fármacos , Cavidade Nasal/inervação , Cavidade Nasal/metabolismo , Nervo Olfatório/anatomia & histologia , Nervo Olfatório/efeitos dos fármacos , Nervo Olfatório/metabolismo , Ratos , Ratos Sprague-Dawley , Nervo Trigêmeo/anatomia & histologia , Nervo Trigêmeo/efeitos dos fármacos , Nervo Trigêmeo/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
Orthop Surg ; 1(4): 311-6, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22009881

RESUMO

OBJECTIVE: To investigate the role of the calcar femorale in stress distribution in the proximal femur. METHODS: Twenty-five specimens of proximal femurs were fixed to simulate single-limb stance. Strain gauges were applied to record the strain under different loads. Strain values of 27 selected sites in the proximal femur were recorded and analyzed at the level of 100 N, 200 N, 300 N, 400 N, 500 N, 600 N and 700 N, respectively before and after disruption of the calcar femorale. RESULTS: When a normal load was being borne, strain values measured in the posterior and medial aspects of the proximal femur were greater than those measured in the anterior and lateral aspects, no matter whether the calcar femorale was disrupted or not. However after disruption of the calcar femorale, strain values in the posterior and medial aspects of the proximal femur increased significantly, whereas those of the anterior and lateral aspects decreased significantly. CONCLUSION: The calcar femorale redistributes stress in the proximal femur by decreasing the load in the posterior and medial aspects and increasing the load in the anterior and lateral aspects.


Assuntos
Fêmur/fisiologia , Articulação do Quadril/cirurgia , Prótese de Quadril , Estresse Mecânico , Adulto , Cadáver , Colo do Fêmur , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Adulto Jovem
19.
Neurosci Lett ; 434(2): 212-7, 2008 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-18328626

RESUMO

Compelling evidence has shown that extracellular signal-regulated kinase (ERK) is widely expressed in many tissues, including the brain. In the present work, we investigated the temporospatial alterations of ERK1 immunoreactivity in hippocampus and perifocal cortex, and the expression involved in NGF/VEGF-induced neuroprotective effect. We demonstrated that ERK1 expression was first increased in hippocampal CA3/DG 1 h after reperfusion, then it was also increased 6 h after reperfusion in other brain regions, with a peak at day 1-3, and then gradually decreased to basal level at day 14. The expression of caspase-3 was strongly increased 1 h after reperfusion, with peak demonstrated at 3d. NGF/VEGF significantly inhibited the expression of ERK1 and caspase-3. These results suggest that ERK1 signaling pathway may be involved in neuronal cell death and NGF/VEGF-induced neuroprotective effect and there appeared an association between ERK and caspase-3. Inhibition of the ERK signaling pathway might therefore provide an efficient way to prevent neuronal cell death after ischemic cerebral injuries.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fator de Crescimento Neural/farmacologia , Fármacos Neuroprotetores/farmacologia , Fator A de Crescimento do Endotélio Vascular/farmacologia , Animais , Apoptose/fisiologia , Isquemia Encefálica/patologia , Caspase 3/metabolismo , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Hipocampo/metabolismo , Hipocampo/patologia , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Masculino , Fator de Crescimento Neural/metabolismo , Fármacos Neuroprotetores/metabolismo , Coelhos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
20.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 25(4): 349-53, 2007 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-17896489

RESUMO

OBJECTIVE: To investigate the imagery changes of the upper airway and the surrounding soft tissues of local adults with non-apnea who used snore guard and to provide experimental data for the clinical diagnosis and treatment of obstructive sleep apnea syndrome (OSAS). METHODS: Thirty students with non-apnea from Hebei medical university were chosen, and magnetic resonance imaging (MRI) was used to measure the changes of the upper airway and the surrounding soft tissues after snore guards were used. SPSS 105 software was used to analyze statistically. RESULTS: After the snore guard was put into oral cavity, the change of the average section and volume of the nasopharynx, the palatopharynx, the hypopharynx and the glossopharynx were statistically significant. The average sagittal size, the average horizontal size of the nasopharynx, the palatopharynx, the hypopharynx and the glossopharynx were increased statistically. The ratio of sagittal size, the horizontal sizand the in the hypopharynx and the glossopharynx changed statistically important. There was a decrease of the soft palate, the shape, the height, and the length of the tongue, the difference was statistically significant. The results demonstrated that snore guard affected the upper airway mainly by changing the volume and the shape of the upper airway, there was an obvious increase of the pharynx. The results also showed that snore guard could increase the width (both sagittal and horizontal) of the upper airway and could change the shape of the surrounding soft tissues, which caused air way more smooth. Snore guard could make the indexes of soft palate and tongue change decreasingly, resulted in the straight stand up of the tongue and the forwardness of the soft palate. CONCLUSION: Snore guard is an effective and convenient instrument for treating the patients with OSAS.


Assuntos
Palato Mole , Apneia Obstrutiva do Sono , Adulto , Oclusão Dentária , Humanos , Imageamento por Ressonância Magnética , Masculino , Faringe , Língua
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