RESUMO
Objective: To trace and characterize the whole genome of SARS-CoV-2 of confirmed cases in the outbreak of COVID-19 on July 31, 2021 in Henan Province. Method: Genome-wide sequencing and comparative analysis were performed on positive nucleic acid samples of SARS-CoV-2 from 167 local cases related to the epidemic on July 31, 2021, to analyze the consistency and evolution of the whole genome sequence of virus. Results: Through high-throughput sequencing, a total of 106 cases of SARS-CoV-2 whole genome sequences were obtained. The results of genome analysis showed that the whole genome sequences of 106 cases belonged to the VOC/Delta variant strain (B.1.617.2 clade), and the whole genome sequences of 106 cases were shared with the genomes of 3 imported cases from Myanmar admitted to a hospital in Zhengzhou. On the basis of 45 nucleotide sites, 1-5 nucleotide variation sites were added, and the genome sequence was highly homologous. Conclusion: Combined with the comprehensive analysis of viral genomics, transmission path simulation experiments and epidemiology, it is determined that the local new epidemic in Henan Province is caused by imported cases in the nosocomial area, and the spillover has caused localized infection in the community. At the same time, it spills over to some provincial cities and results in localized clustered epidemics.
Assuntos
COVID-19 , Epidemias , Humanos , SARS-CoV-2/genética , Genoma Viral , FilogeniaRESUMO
BACKGROUND: The therapeutic value of repeat hepatic resection (rHR) or radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma (HCC) is unknown. This study aimed to investigate the safety and efficacy of rHR or RFA. METHODS: This was a retrospective multicentre study of patients with recurrent HCC within the Milan criteria who underwent rHR or RFA at nine university hospitals in China and Italy between January 2003 and January 2018. Survival after rHR or RFA was examined in unadjusted analyses and after propensity score matching (1 : 1). RESULTS: Of 847 patients included, 307 and 540 underwent rHR and RFA respectively. Median overall survival was 73.5 and 67.0 months after rHR and RFA respectively (hazard ratio 1.01 (95 per cent c.i. 0.81 to 1.26)). Median recurrence-free survival was longer after rHR versus RFA (23.6 versus 15.2 months; hazard ratio 0.76 (95 per cent c.i. 0.65 to 0.89)). These results were confirmed after propensity score matching. RFA was associated with lower morbidity of grade 3 and above (0.6 versus 6.2 per cent; P < 0.001) and shorter hospital stay (8.0 versus 3.0 days, P < 0.001) than rHR. CONCLUSION: rHR was associated with longer recurrence-free survival but not overall survival compared with RFA.
Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Ablação por Radiofrequência , Intervalo Livre de Doença , Feminino , Hepatectomia/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Ablação por Radiofrequência/efeitos adversos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The Child-Pugh (CP) score is used widely to assess liver function and predict postoperative outcomes in patients with hepatocellular carcinoma (HCC). Recently, the albumin-bilirubin (ALBI) score has been validated as a predictor of overall survival in these patients. This study aimed to compare the ability of the ALBI and CP scores to predict outcomes in patients with HCC after liver resection with curative intent. METHODS: Consecutive patients who underwent liver resection with curative intent for HCC between January 2007 and July 2013 were included in this retrospective study. The performance of the ALBI score in predicting postoperative liver failure (PHLF) and long-term survival was compared with that of the CP score. RESULTS: A total of 1242 patients were enrolled. Of these, 166 (13·4 per cent) experienced PHLF. The area under the receiver operating characteristic (ROC) curve of the ALBI score for predicting PHLF was greater than that of the CP score (0·723 versus 0·607; P < 0·001). Similar to findings for CP grade, the incidence and severity of PHLF increased with increasing ALBI grade. The ALBI grade stratified patients into at least two distinct overall survival cohorts (P < 0·001), whereas the CP grade did not. The ALBI grade also classified patients with CP grade A disease into two distinct overall survival cohorts (P < 0·001), and overall survival rates in the group with poorer survival were similar to those in the majority of patients with CP grade B disease. Both CP and ALBI scores had low power in predicting disease-free survival. CONCLUSION: The ALBI grade predicted PHLF and overall survival in patients with HCC undergoing liver resection with curative intent more accurately than the CP grade.
Assuntos
Bilirrubina/sangue , Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Falência Hepática/diagnóstico , Neoplasias Hepáticas/cirurgia , Albumina Sérica/análise , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Feminino , Hepatectomia/mortalidade , Humanos , Falência Hepática/etiologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
OBJECTIVE: To investigate the influence of the PI3K/AKT signaling pathway on the proportion and characteristics of the stem-like CD90(+) subpopulation of the human hepatocellular carcinoma (HCC) cell line MHCC-97. METHODS: MHCC-97H cultures were treated with the PI3K/AKT pathway inhibitor LY294002. The proportion of the CD90(+) subpopulation was determined by flow cytometry, and the expression of related proteins was measured by Western blot. The clonogenicity of CD90(+) and CD90(-) cells was measured by plate colony formation assay. The tumorigenicity was compared between CD90(+) and CD90(-) subpopulations (with different concentrations) in xenograft experiments in nude mice, and the changes in tumorigenicity after the addition of LY294002 were evaluated. The changes in the expression of CD90, SHP2, P-AKT, and AKT in CD90(+) and CD90(-) cell xenografts after the addition of LY294002 were examined. Data were analyzed using t test. RESULTS: LY294002 was capable of reducing the proportion of CD90(+) HCC stem cells from 2.98%±0.08% to 0.78%±0.08% (t = 32.400, P < 0.01) and reducing the clonogenicity of CD90(+) subpopulation from 95.13%±3.78% to 61.82%±7.23% (t = 7.617, P < 0.01). However, it showed no significant effect on the clonogenicity of CD90(-) subpopulation. LY294002 also reduced the tumorigenicity of CD90(+) subpopulation and the expression of CD90, SHP2, and P-AKT in related HCC stem cells, but it did not significantly affect the expression of AKT. LY294002 had no significant inhibitory effect on the tumorigenicity of CD90(-) cells. CONCLUSION: The CD90(+) subpopulation of MHCC-97H cells has the characteristics of stem cells and is dependent on the PI3K/AKT signaling pathway.
Assuntos
Carcinoma Hepatocelular/metabolismo , Células-Tronco Neoplásicas/citologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Antígenos Thy-1/metabolismo , Animais , Linhagem Celular Tumoral , Cromonas , Humanos , Neoplasias Hepáticas/metabolismo , Camundongos , Camundongos Nus , Morfolinas , Transplante de NeoplasiasRESUMO
To study the effects of excision repair cross-complementing 1 (ERCC1) on the pathophysiological process of brain ischemia, we examined the changes in ERCC1 expression, as well as the functional significance of ERCC1 in the rat brain following middle cerebral artery occlusion (MCAO). The results were as follows: (1) ERCC1 immunopositive cells were widely distributed in various brain regions. ERCC1 expression was localized to the nuclei of neurons and astrocytes. (2) ERCC1 expression, as determined by western blot, increased at 3 days, remaining until 14 days, in the ipsilateral cortex and striatum following MCAO. Immunohistochemical analysis demonstrated that ischemia induced increased ERCC1 expression within the periinfarct core, with increasingly less expression toward the core. (3) Knockdown of ERCC1 expression by intraventricular injection of antisense plasmids increased DNA damage and infarct volume in the ischemic brain. (4) ERCC1 overproduction, by injection of expression plasmids, significantly reduced infarct volume and the accumulation of DNA-damaged neurons. Taken together, these results indicate that both endogenous ERCC1 and exogenous ERCC1 have an important neuroprotective function in the brain. In addition, administration of ERCC1 to the brain could prove to be a successful strategy for neuronal protection against ischemic injury.
Assuntos
Isquemia Encefálica/prevenção & controle , Encéfalo/metabolismo , Reparo do DNA/fisiologia , Proteínas de Ligação a DNA/metabolismo , Endonucleases/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Fármacos Neuroprotetores/farmacologia , Animais , Western Blotting , Encéfalo/patologia , Isquemia Encefálica/patologia , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/fisiologia , DNA Antissenso , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Endonucleases/genética , Técnicas de Silenciamento de Genes , Proteínas de Fluorescência Verde/metabolismo , Infarto da Artéria Cerebral Média/patologia , Masculino , Fármacos Neuroprotetores/administração & dosagem , Plasmídeos , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes de Fusão/metabolismo , Coloração e Rotulagem , Fatores de Tempo , Distribuição TecidualRESUMO
The gene encoding human interleukin-2 (IL-2) has been cloned from human spleen cells, peripheral blood lymphocytes, and the Jurkat cell line. Nucleotide sequence analysis of the gene revealed that the encoded IL-2 protein has three cysteines located at amino acid residues 58, 105, and 125 of the mature protein. Site-specific mutagenesis procedures were used to modify the IL-2 gene by changing each of the cysteine codons individually to serine codons. Substitution of serine for cysteine residues at either position 58 or 105 of the IL-2 protein substantially reduced biological activity, indicating that the cysteines at these positions are necessary for maintenance of the biologically active conformation and may therefore be linked by a disulfide bridge. The modified IL-2 protein containing a substitution at position 125 retained full biological activity, suggesting that the cysteine at this position is not involved in a disulfide bond and that a free sulfhydryl group at that position is not necessary for receptor binding.
Assuntos
Interleucina-2/genética , Mutação , Sequência de Aminoácidos , Sequência de Bases , Linhagem Celular , Cisteína/metabolismo , DNA Recombinante/metabolismo , Escherichia coli/genética , Genes , Humanos , Receptores Imunológicos/metabolismo , Receptores de Interleucina-2 , Serina/metabolismo , Relação Estrutura-AtividadeRESUMO
MicroRNAs (miRNAs) are vital in the regulation of tumor progression and invasion. Dysregulation of miRNAs has been linked to the development of various types of human cancers, including non-small-cell lung cancer (NSCLC). However, the effect of miRNA-34a (miR-34a), a key regulator of tumor suppression, on the tumorigenesis of NSCLC has not been fully elaborated. Herein, we reveal that miR-34a is significantly downregulated in NSCLC tissues and cell lines, suggesting that miR-34a might function as a tumor suppressor in lung cancer. We also confirmed that epidermal growth factor receptor (EGFR) is a direct target of miR-34a, and our data reveal that siRNA knockdown of EGFR can inhibit cell proliferation, promote apoptosis and arrest cell-cycle progression. In addition, EGFR can reverse the suppressive function of miR-34a overexpression on proliferation and cell apoptosis. Furthermore, in vivo experiments demonstrated that miR-34a suppress tumor growth, both in the A549 xenograft model, as well as in the metastatic tumors in nude mice. Taken together, our findings suggest that miR-34a inhibits NSCLC tumor growth and metastasis through targeting EGFR.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Cloroquina/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Citocinas/metabolismo , Progressão da Doença , Pneumonia Viral/tratamento farmacológico , Resultado do Tratamento , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Quimioterapia Combinada , Hospitalização , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Medição de Risco , Índice de Gravidade de Doença , Tratamento Farmacológico da COVID-19RESUMO
Quantitative assays for viral nucleic acids have been instrumental in monitoring the response of patients to various antiviral therapies. The level of viraemia is predictive of clinical outcome in that a reduced risk of progression to AIDS or death was observed with lower plasma human immunodeficiency virus (HIV) RNA levels. Rebound in viral levels often signals therapeutic failures, some of which are associated with the development of drug resistance. Quantitative plasma assays for HIV, hepatitis C virus (HCV), cytomegalovirus (CMV) and hepatitis B virus (HBV) have been developed. Over time, modifications to these assays have been required to meet new demands. For example, as antiviral therapies have become more effective, HIV and HCV assays of greater sensitivity are required in order to follow patients for longer periods of time and to fully assess the extent of viral suppression. For HIV-1, a large percentage of patients treated with combination therapies had viral loads that were below the detection limit of the ultrasensitive assay (50 copies/ml). To assess the residual viral burden in this patient population an assay to quantify HIV-1 proviral DNA in peripheral blood mononuclear cells was developed. Studies to date indicate that proviral DNA remains easily detectable despite undetectable plasma RNA and may be useful in monitoring this patient population. To increase assay throughput, a new generation of quantitative assays that will provide real-time detection and a 6 log10 detection range from a single amplification is under development.
Assuntos
Antivirais/uso terapêutico , Viroses/tratamento farmacológico , Biomarcadores , DNA Viral/análise , DNA Polimerase Dirigida por DNA/metabolismo , Resistência a Medicamentos , HIV/classificação , Humanos , Provírus/genética , Viroses/virologiaRESUMO
The role of excitatory amino acid transporter 1 in neonatal rat neuronal damage was studied following hypoxia-ischemia. To induce hypoxia-ischemia injury, rats on postnatal day 7 were exposed to 8 % oxygen for 2 h following unilateral common carotid artery ligation. According to brain damage scoring based on Cresyl Violet staining, the neuronal damage time-dependently changed in the ischemic regions following hypoxia-ischemia. Immunohistochemical studies showed that excitatory amino acid transporter 1 expression was mainly observed in the cerebral cortex ipsilateral to common carotid artery ligation and markedly increased at 24 h and 48 h following hypoxia-ischemia. Combined with confocal laser scanning microscopic analysis, double staining showed that excitatory amino acid transporter 1 positive staining appeared in neurons as well as astrocytes after hypoxia-ischemia. Most excitatory amino acid transporter 1 positive staining cells exhibited regular morphological characteristics and only a few were double-stained by terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick-end labeling. Down-regulation of excitatory amino acid transporter 1 expression by intraventricular administration of specific antisense oligonucleotide exacerbated neuronal damage in hypoxia-ischemia brain. These results suggest that the increase of excitatory amino acid transporter 1 expression may be involved in a pathophysiological process of hypoxia-ischemia brain damage and may reflect a self-compensative mechanism for protecting neurons from further injury.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Encéfalo/metabolismo , Hipóxia-Isquemia Encefálica/metabolismo , Neurônios/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Sistema X-AG de Transporte de Aminoácidos , Animais , Animais Recém-Nascidos , Benzoxazinas , Encéfalo/patologia , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Lateralidade Funcional , Regulação da Expressão Gênica , Hipocampo/metabolismo , Hipocampo/patologia , Hipóxia-Isquemia Encefálica/patologia , Imuno-Histoquímica , Cinética , Neurônios/patologia , Oxazinas , Fosfopiruvato Hidratase/metabolismo , Ratos , Ratos Sprague-Dawley , Tálamo/metabolismo , Tálamo/patologia , Fatores de TempoRESUMO
In situ hybridization with a digoxigenin-labeled oligonucleotide probe was used to investigate the expression of opioid-receptor-like receptor (ORL1) gene in rat brain. It was observed that ORL1 mRNA is widely expressed in many regions of rat brain, particularly in cerebral cortex, thalamus, hypothalamus, amygdala, hippocampus, septum, habenula, periaqueducted gray, raphe nuclei and locus coeruleus structure. These findings suggest that ORL1 receptor may participate in modulating a number of physiological functions in the brain in addition to pain.
Assuntos
Encéfalo/metabolismo , Receptores Opioides/biossíntese , Animais , Córtex Cerebral/metabolismo , Feminino , Expressão Gênica , Dor/fisiopatologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Receptores Opioides/genética , Tálamo/metabolismo , Receptor de NociceptinaRESUMO
OBJECTIVE: To construct recombinant plasmid with human atrial natriuretic peptide (ANP) gene in fusion form for stable and high level expression of genetic engineering product ANP in E. coli system. METHODS: Plasmids with ANP fusion gene were constructed by PCR and sub-cloning and fusion protein was expressed in E. coli system. High level expression of the fusion genes was enhanced by linking operons in tandem. ANP was released from the fusion protein with thrombin treatment and purified by chromatography. Genetic-engineered ANP was evaluated with the drug production requirement, and produced ANP was tested for its effects of lowering blood pressure and diuresis in vivo and vasodilation in vitro. RESULTS: A series of 4 plasmid pCW111-114, containing 1 to 4 gene operons respectively, were constructed, and the yields of fusion protein were 46%, 54.8%, 56.1% and 60.1% of total cell protein. Fusion protein in the form of inclusion body was isolated and purified, and then treated with thrombin to release ANP. After purification using chromatography columns, at least 3 mg/L culture of ANP with the purity higher than 96% was produced in shaking flask. Primary pharmacological evaluation showed the produced ANP had the effects of blood pressure lowering in vivo and diuresis in vivo and vasodilation in vitro, which was similar to the activity of standard ANP. CONCLUSIONS: By the protocol of fusion gene cloning and expression, the human ANP was produced successfully in E. coli system.
Assuntos
Fator Natriurético Atrial/biossíntese , Animais , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/farmacologia , Escherichia coli/genética , Expressão Gênica , Engenharia Genética , Plasmídeos/genética , Ratos , Ratos Wistar , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/farmacologia , TrombinaRESUMO
Lysogenization by a c1ts variant of coliphage P1, P1c1.100, markedly increased the frequency of reversion of a galT::IS1 mutation. The formation of Gal+ colonies presumably occurs by microhomologous recombination between the 9-base-pair repeats in galT (CGCCGCTAC) generated by the transposition of IS1. The responsible P1 gene, ref, has been cloned and sequenced. ref encodes a 22.8-kilodalton protein and is located near the P1 site-specific recombination function, cre. Expression of ref was repressed by P1 c+. The absence of a distinctive ribosome-binding site is consistent with a poor translation of ref from an expression vector in vivo. Placement of a ribosome-binding site before ref resulted in the extensive synthesis of the Ref protein. Ref stimulated precise excision in recB or himA cells, but not in recA mutants. Ref was active in lexA3 mutants, suggesting that the recombination activity of RecA was directly involved in the reaction. We have constructed a P1c1.100 ref::Tn10 mutant. The absence of Ref did not appear to restrict dramatically the ability of P1 to grow lytically or to form lysogens. Thus, the role of ref in the physiology of P1 remains to be determined.
Assuntos
Colífagos/genética , Elementos de DNA Transponíveis , Escherichia coli/genética , Genes Virais , Recombinação Genética , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Análise Mutacional de DNA , Dados de Sequência Molecular , Recombinases Rec A/fisiologia , Mapeamento por RestriçãoRESUMO
AIM: To study the protective effect of melatonin against neuronal injury and the possible roles of alteration in the expression of bcl-2 and bax following brain ischemia. METHODS: Brain ischemia was induced by left middle cerebral artery occlusion (MCAO) for 60 min in rats. Brain damage was evaluated by the infarct area and the neuronal cell counting. The expression of bcl-2 and bax was analyzed by immunohistochemical method. RESULTS: Melatonin decreased the infarct area and prevented the neuronal death after 24-h reperfusion following 1-h MCAO. Melatonin given before the ischemia enhanced the expression of bcl-2 in the penumbra area and had no significant effect on the expression of bax. CONCLUSION: Melatonin effectively attenuated ischemic brain injury and increased the expression of neuronal bcl-2 in the ischemic brain, indicating that the protective effect of melatonin was associated with up-regulation of bcl-2 in ischemia-induced neuronal death.
Assuntos
Encéfalo/patologia , Melatonina/farmacologia , Fármacos Neuroprotetores/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Traumatismo por Reperfusão/patologia , Animais , Encéfalo/metabolismo , Isquemia Encefálica/complicações , Masculino , Neurônios/efeitos dos fármacos , Proteínas Proto-Oncogênicas/biossíntese , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Proteína X Associada a bcl-2RESUMO
Tumor necrosis factor (TNF) is a monocyte-derived cytotoxin that has been implicated in tumor regression, septic shock, and cachexia. The mechanism by which TNF induces these different disease states is unclear. We have identified and characterized a novel, rapidly inducible cell surface cytotoxic integral transmembrane form of TNF. The existence and behavior of this novel form of TNF may explain the complex physiology of this molecule. We suggest that activated monocytes synthesize transmembrane TNF at the site of inflammation and kill their targets by either cell-to-cell contact or local release of the TNF secretory component. In contrast, septic shock and cachexia may result from either acute or chronic systemic activation of monocytes, resulting in the widespread release of TNF secretory component into the circulation of the affected individual. We further suggest that cell borne cytokines and cytotoxins may be the primary mediators of directed inflammatory responses.
Assuntos
Proteínas de Membrana/fisiologia , Monócitos/metabolismo , Fator de Necrose Tumoral alfa/fisiologia , Células Cultivadas , Citotoxinas , Genes , Humanos , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Peso Molecular , Plasmídeos , Biossíntese de Proteínas , Transcrição Gênica , Transfecção , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genéticaRESUMO
Human fibroblast interferon has three cysteine residues, located at amino acid positions 17, 31, and 141. Using the technique of site-specific mutagenesis with a synthetic oligonucleotide primer, we changed the codon for cysteine-17 to a codon for serine. The resulting interferon, IFN-beta Ser-17, retains the antiviral, natural killer cell activation, and antiproliferative activities of native fibroblast interferon. The purified IFN-beta Ser-17 protein has an antiviral specific activity of 2 X 10(8) units/mg, similar to that of purified native fibroblast interferon. In addition, the purified protein is stable to long-term storage at -70 degrees C.
Assuntos
Genes , Interferon Tipo I/genética , Mutação , Sequência de Aminoácidos , Sequência de Bases , Linhagem Celular , Clonagem Molecular , Cisteína , Humanos , Interferon Tipo I/toxicidade , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Ativação Linfocitária , Oligodesoxirribonucleotídeos/toxicidade , Plasmídeos , Pele , Vírus da Estomatite Vesicular Indiana/efeitos dos fármacosRESUMO
AIM: To clarify the role of vascular endothelial growth factor (VEGF) in neuronal damage induced by cerebral ischemia. METHODS: Expression of VEGF in adult rat brain was measured by immunohistochemistry. Transient middle cerebral artery occlusion (MCAO) model was induced by placing a nylon thread in the lumen of the internal carotid artery. The infarct volume was shown with 2,3,5-triphenyltetrazolium chloride (TTC) staining and quantitated by computer image analyzer with and without VEGF antibody treatment. RESULTS: VEGF expression was widely distributed in neuronal cells besides vascular endothelial cells, and the neuronal distribution of VEGF was specific. After intraventricular treatment with VEGF antibody (0.1 g.L-1 daily, for 7 d following the ischemia), infarct volume in the antibody treatment was increased versus vehicle-treated rats [(21.6 +/- 2.7 vs 16 +/- 6) mm3, P < 0.05] respectively. CONCLUSION: Intraventricular injection of VEGF antibody increased the infarct volume after focal cerebral ischemia in rats, suggesting that expression of neuronal VEGF may be one of neuronal protective mechanisms.
Assuntos
Encéfalo/patologia , Fatores de Crescimento Endotelial/biossíntese , Ataque Isquêmico Transitório/patologia , Linfocinas/biossíntese , Animais , Anticorpos , Encéfalo/metabolismo , Fatores de Crescimento Endotelial/fisiologia , Ataque Isquêmico Transitório/metabolismo , Linfocinas/fisiologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
AIM: To study the effect of dextromethorphan (DM) in focal cerebral ischemia. METHODS: The c-fos protein was detected immunohistochemically in the brain of rats after focal cerebral ischemia (induced by placing a nylon thread in the lumen of the internal carotid artery) with and without treatment with DM. RESULTS: Focal cerebral ischemia induced c-fos protein expression outside the core territory of the middle cerebral artery (MCA) and neuronal damage in the core territory of the MCA. There was an evident expression of c-fos protein in the ipsilateral regions outside the MCA territory (e.g. cingulate cortices, piriform cortices and entorhinal cortices), and in the contralateral regions of hippocampus after 4-h reperfusion following 1-h MCA occlusion. But morphological results showed severe edema and neuronal damage in the core territory and the ipsilateral hippocampus. DM blocked both the c-fos protein induction and neuronal damage in all regions. CONCLUSION: DM reduced c-fos protein expression and blocked the neuronal damage after focal cerebral ischemia.