RESUMO
Objective: To compare the intraoperative neurophysiological monitoring (IONM) results between patients with arthrogryposis multiplex congenita (AMC) and adolescent idiopathic scoliosis (AIS) and to analyze the influence of congenital spinal deformity on IONM in AMC patients, thus to evaluate the efficiency of IONM in AMC patients. Methods: A cross-sectional study. The clinical data of 19 AMC patients underwent correction surgery from July 2013 to January 2022 in Nanjing Drum Tower Hospital were retrospectively reviewed. There were 13 males and 6 females with a mean age of (15.2±5.6) years, and the average Cobb angle of main curve was 60.8°±27.7°. And 57 female AIS patients of similar age and curve type with the AMC patients during the same period were selected as the control group, with an average age of (14.6±4.4) years and a mean Cobb angle of 55.2°±14.2°. The latency and amplitude of samatosensory evoked potentials (SSEPs) and transcranial electric motor evoked potentials (TCeMEPs) were compared between the two groups. The difference in IONM data between AMC patients with and without congenital spinal deformity was also evaluated. Results: The success rates of SSEPs and TCeMEPs were 100% and 14/19 for AMC patients, 100% and 100% for AIS patients. The SSEPs-P40 latency, SSEPs-N50 latency, SSEPs-amplitude, TCeMEPs-latency, TCeMEPs-amplitude showed no significant difference between AMC patients and AIS patients (P>0.05 for all). The side-difference of TCeMEPs-amplitude showed an increasing trend in AMC patients when compared with that in AIS patients, but there was no statistical difference between the two groups [(147.0±185.6) µV vs (68.1±311.4) µV, P=0.198]. The SSEPs-amplitude value was (1.4±1.1) µV on concave side in AMC patients with congenital spinal deformity, and it was (2.6±1.2) µV on concave side in AMC patients without congenital spinal deformity (P=0.041). The SSEPs-amplitude value was (1.4±0.8) µV on convex side in AMC patients with congenital spinal deformity, and it was (2.6±1.3) µV on convex side in AMC patients without congenital spinal deformity (P=0.028). Conclusions: The values of SSEPs-P40 latency, SSEPs-N50 latency, SSEPs-amplitude, TCeMEPs-latency and TCeMEPs-amplitude are similar in AMC and AIS patients. The SSEPs-amplitude of AMC patients with congenital spinal deformity is lower than that of AMC patients without congenital spinal deformity.
Assuntos
Artrogripose , Monitorização Neurofisiológica Intraoperatória , Cifose , Escoliose , Masculino , Humanos , Adolescente , Feminino , Criança , Adulto Jovem , Adulto , Escoliose/cirurgia , Estudos Transversais , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate the efficacy of intravitreal conbercept (IVC) in pars plana vitrectomy (PPV) for patients with proliferative diabetic retinopathy (PDR). METHODS: A meta-analysis of randomized control trials (RCTs) using online databases was performed. The intraoperative outcome measures were the incidence of intraoperative bleeding and endodiathermy application, and the mean surgical time. The postoperative outcome measures were mean change in best-corrected visual acuity (BCVA) from baseline, postoperative vitreous clear-up time and incidence of recurrent vitreous hemorrhage (VH). RESULTS: Eight RCTs were selected for meta-analysis. They included 409 eyes (215 eyes in IVC group and 194 eyes in no conbercept group). Preoperative IVC application was associated with less intraoperative bleeding and endodiathermy applications (RR = 0.34, 95% CI, 0.23-0.50, P < 0.00001, and RR = 0.26, 95% CI, 0.12-0.56, P = 0.0005) compared to no conbercept. It also shortened surgical time (WMD = -15.87, 95% CI, -22.04 to -9.69, P < 0.00001). In addition, preoperative or intraoperative IVC achieved better BCVA outcome (WMD = -0.37, 95% CI, -0.62 to -0.13, P = 0.003), shorter vitreous clear-up time postoperatively (WMD = -5.44, 95% CI, -6.31 to -4.57, P < 0.00001) and a lower rate of VH recurrence (RR = 0.45, 95% CI, 0.22-0.91, P = 0.03). CONCLUSION: IVC is an effective adjuvant in PPV for PDR, with better intraoperative and postoperative outcomes.
Assuntos
Diabetes Mellitus , Retinopatia Diabética , Inibidores da Angiogênese/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/cirurgia , Humanos , Injeções Intravítreas , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes de Fusão , Vitrectomia/efeitos adversos , Hemorragia Vítrea/epidemiologia , Hemorragia Vítrea/prevenção & controleRESUMO
PURPOSE: To assess the incidence of iatrogenic retinal breaks (IRBs) and postoperative retinal detachments (RDs) in microincision vitrectomy surgery (MIVS) compared with 20-gauge (20 G) vitrectomy. METHODS: A comprehensive literature search was performed to find relevant studies and a meta-analysis of the IRBs and postoperative RDs rates after 20 G vitrectomy versus MIVS was conducted. RESULTS: Thirty-two studies were selected, including 14,373 eyes (6932 eyes in the 20 G group, 7441 eyes in the MIVS group). The meta-analysis demonstrated that the incidence of IRBs was significantly higher in 20 G vitrectomy vs. MIVS (OR = 2.22, 95% CI, 1.93-2.57, P < 0.00001) and in a subanalysis vs. 23 G MIVS (OR = 2.19, 95% CI, 1.87-2.56, P < 0.00001) and vs. 25 G MIVS (OR = 2.27, 95% CI, 1.62-3.18, P < 0.00001). Similar result was obtained in a subanalysis for macular surgery (OR = 2.44, 95% CI, 1.99-2.99, P < 0.00001), and also for sclerotomy-related IRBs (OR = 3.73, 95% CI, 2.55-5.44, P < 0.00001), but not for surgically induced posterior vitreous detachment-related IRBs (OR = 1.59, 95% CI, 0.89-2.84, P = 0.12). The incidence of postoperative RDs in 20 G vitrectomy was significantly higher compared to MIVS (OR = 1.72, 95% CI, 1.21-2.46, P = 0.003) and in a subanalysis vs. 23 G MIVS (OR = 2.45, 95% CI, 1.50-4.00, P = 0.0003), but not for 25 G MIVS (OR = 1.01, 95% CI, 0.63-1.64, P = 0.96). Similar result was obtained in a subanalysis for macular surgery (OR = 1.89, 95% CI, 1.26-2.85, P = 0.002). CONCLUSION: This meta-analysis demonstrated that MIVS is associated with a lower risk of IRBs and postoperative RDs compared to 20 G vitrectomy.
Assuntos
Complicações Pós-Operatórias , Descolamento Retiniano/epidemiologia , Perfurações Retinianas/epidemiologia , Vitrectomia/métodos , Idoso , Feminino , Humanos , Doença Iatrogênica , Incidência , Masculino , Microcirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Acuidade Visual , Corpo Vítreo/cirurgiaRESUMO
Objective: To investigate the correlated factors of height gain (ΔSH) after posterior spinal correction surgery in Lenke 1 adolescent idiopathic scoliosis (AIS), and to propose the predictive model of ΔSH. Methods: From 2013 to 2015, a total of 150 Lenke 1 AIS patients undergoing posterior spinal correction surgery were included in the study, with the age of (14.3±2.9) years. The Cobb angle of major curve, thoracic kyphosis (TK) and lumbar lordosis (LL) were measured on both pre-op and post-op standing whole spine x-rays. The change in Cobb angle, TK and LL were calculated. The difference between pre-operation and post-operation was compared and the linear regression analysis was used for the predictive model of ΔSH. Results: The pre-op and post-op values were (41.6±3.0)cm and (43.9±2.7)cm for spinal height (SH)[ΔSH=(2.4±0.8)cm, P=0.000]; (50.5±10.4)° and (14.6±6.4)° for Cobb angle (P=0.000). The Pearson correlation analysis showed that ΔSH was significantly correlated with pre-op SH (P=0.000), pre-op Cobb angle (P=0.000), pre-op TK (P=0.000), post-op SH (P=0.020), post-op Cobb angle (P=0.000), change in Cobb angle (P=0.000) and change in TK (P=0.000). The linear regression model 1 revealed that ΔSH was linearly correlated with change in Cobb angle (P=0.000) as well as change in TK (P=0.000); the linear regression model 2 showed that the pre-op Cobb angle (P=0.000) and pre-op TK (P=0.020) could be used for the pre-op prediction of ΔSH. Conclusions: The positively correlated factors of ΔSH include pre-op and post-op Cobb angle, TK, change in Cobb angle and change in TK. High pre-op Cobb angle and TK indicates high height gain in Lenke 1 AIS patients.
Assuntos
Cifose , Lordose , Escoliose , Fusão Vertebral , Adolescente , Criança , Humanos , Radiografia , Estudos Retrospectivos , Escoliose/cirurgia , Coluna Vertebral , Vértebras Torácicas , Resultado do TratamentoRESUMO
INTRODUCTION: To assess the risk factors of Gleason sum upgrading between biopsy and radical prostatectomy (RP) and update the nomogram for the prediction of Gleason sum upgrading. METHODS: The study cohort consisted of 237 Chinese prostate adenocarcinoma patients who underwent 10-core prostate biopsy and subsequently received RP in Huashan Hospital from February 2011 to May 2015. The main outcome of our study was Gleason sum upgrading between biopsy and RP pathology. Univariate and multivariate logistic regression models were conducted to explore the potential predictors, and ultimately to build the nomograms. The prediction model was further evaluated for its ability to predict significant upgrading in patients with biopsy Gleason sum<8. RESULTS: In the main cohort of all the patients, Gleason sum upgrading was observed in 62 (26.16%) patients. The pre-operative prostate-specific antigen (PSA) level, biopsy Gleason sum, and digital rectal examination were used in building the nomogram, which was validated internally with a bootstrap-corrected concordance index of 0.787. In the sub-cohort of 115 patients with standardized biopsy details, Gleason sum upgrading was observed in 31 (26.96%) patients. The pre-operative PSA level, biopsy Gleason sum, and number of positive cores were used in the nomogram, which was also validated internally with a bootstrap-corrected concordance index of 0.833. These two nomograms both demonstrated satisfactory statistical performance for predicting significant upgrading. CONCLUSIONS: Updated nomograms to predict Gleason sum upgrading in Chinese population between biopsy and RP were developed, demonstrating good statistical performance upon internal validation.
Assuntos
Adenocarcinoma/patologia , Nomogramas , Próstata/patologia , Prostatectomia , Neoplasias da Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Biópsia , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prostatectomia/métodos , Estudos Retrospectivos , Medição de Risco , Fatores de RiscoRESUMO
The first human infection with avian influenza A(H7N9) virus was reported in Shanghai, China in March 2013. An additional 32 cases of human H7N9 infection were identified in the following months from March to April 2013 in Shanghai. Here we conducted a case-control study of the patients with H7N9 infection (n = 25) using controls matched by age, sex, and residence to determine risk factors for H7N9 infection. Our findings suggest that chronic disease and frequency of visiting a live poultry market (>10 times, or 1-9 times during the 2 weeks before illness onset) were likely to be significantly associated with H7N9 infection, with the odds ratios being 4.07 [95% confidence interval (CI) 1.32-12.56], 10.61 (95% CI 1.85-60.74), and 3.76 (95% CI 1.31-10.79), respectively. Effective strategies for live poultry market control should be reinforced and ongoing education of the public is warranted to promote behavioural changes that can help to eliminate direct or indirect contact with influenza A(H7N9) virus.
Assuntos
Subtipo H7N9 do Vírus da Influenza A/fisiologia , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , China/epidemiologia , Cidades/epidemiologia , Feminino , Humanos , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
The aim of the present study was to determine the effect of the combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and adriamycin (ADM) on the human breast cancer cell line MCF-7 and to identify potential mechanisms of apoptosis. Cell viability was analyzed by the MTT assay and the synergistic effect was assessed by the Webb coefficient. Apoptosis was quantified using the annexin V-FITC and propidium iodide staining flow cytometry. The mRNA expression of TRAIL receptors was measured by RT-PCR. Changes in the quantities of Bax and caspase-9 proteins were determined by Western blot. MCF-7 cells were relatively resistant to TRAIL (IC50 >10 microg/mL), while MCF-7 cells were sensitive to ADM (IC50 <10 microg/mL). A subtoxic concentration of ADM (0.5 microg/mL) combined with 0.1, 1, or 10 microg/mL TRAIL had a synergistic cytotoxic effect on MCF-7 cells, which was more marked with the combination of TRAIL (0.1 microg/mL) and ADM (0.5 microg/mL). In addition, the combined treatment with TRAIL and ADM significantly increased cell apoptosis from 9.8% (TRAIL) or 17% (ADM) to 38.7%, resulting in a synergistic apoptotic effect, which is proposed to be mediated by up-regulation of DR4 and DR5 mRNA expression and increased expression of Bax and caspase-9 proteins. These results suggest that the combination of TRAIL and ADM might be a promising therapy for breast cancer.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Doxorrubicina/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Western Blotting , Caspase 9/análise , Linhagem Celular Tumoral , Sinergismo Farmacológico , Citometria de Fluxo , Humanos , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína X Associada a bcl-2/análiseRESUMO
The aim of the present study was to determine the effect of the combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and adriamycin (ADM) on the human breast cancer cell line MCF-7 and to identify potential mechanisms of apoptosis. Cell viability was analyzed by the MTT assay and the synergistic effect was assessed by the Webb coefficient. Apoptosis was quantified using the annexin V-FITC and propidium iodide staining flow cytometry. The mRNA expression of TRAIL receptors was measured by RT-PCR. Changes in the quantities of Bax and caspase-9 proteins were determined by Western blot. MCF-7 cells were relatively resistant to TRAIL (IC50 >10 µg/mL), while MCF-7 cells were sensitive to ADM (IC50 <10 µg/mL). A subtoxic concentration of ADM (0.5 µg/mL) combined with 0.1, 1, or 10 µg/mL TRAIL had a synergistic cytotoxic effect on MCF-7 cells, which was more marked with the combination of TRAIL (0.1 µg/mL) and ADM (0.5 µg/mL). In addition, the combined treatment with TRAIL and ADM significantly increased cell apoptosis from 9.8 percent (TRAIL) or 17 percent (ADM) to 38.7 percent, resulting in a synergistic apoptotic effect, which is proposed to be mediated by up-regulation of DR4 and DR5 mRNA expression and increased expression of Bax and caspase-9 proteins. These results suggest that the combination of TRAIL and ADM might be a promising therapy for breast cancer.
Assuntos
Humanos , Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Doxorrubicina/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Western Blotting , Linhagem Celular Tumoral , Caspase 9/análise , Sinergismo Farmacológico , Citometria de Fluxo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , RNA Mensageiro/análise , /análiseRESUMO
OBJECTIVE: To investigate whether recombinant human growth hormone (rhGH) reduces mortality and protects against Staphylococcus aureus sepsis-induced acute lung injury. METHODS: The bacteria-positive rate of blood smears and bacteria colony counts in bacteria plate culture, TNFalpha and IL-10 plasma levels, lung injury score, expression of intercellular adhesion molecule-1 (ICAM-1) as well as activation of nuclear factor-kappa B (NF-kappaB) in the lungs were determined 6, 12 and 24 h after 140 KM mice were injected with physiologic saline (i.p. group C, n = 20); S. aureus E311122 (1.75 x 10(12) cfu/L, 40 ml/kg, i.p. group S, n = 60); or S. aureus (as group S) with a subsequent treatment of rhGH (1.0 U kg(-1) day(-1)), i.m. group T, n = 60). The cumulative survival rate of an additional 15 mice from each group was followed for 7 days post S. aureus injection. RESULTS: rhGH treatment significantly increased IL-10 plasma levels and the 7-day cumulative survival rate, whereas the bacteria-positive rate of blood smears, bacteria colony counts in bacteria plate cultures, lung injury score, ICAM-1 and NF-kappaB expression in the lungs were significantly reduced. In addition, rhGH treatment significantly suppressed the S. aureus sepsis-induced elevation of TNFalpha plasma levels. CONCLUSIONS: These results indicate an ability of rhGH to prevent S. aureus sepsis-induced acute lung injury in mice, which may be attributed to attenuation of increased plasma TNFalpha levels, and elevated IL-10 plasma levels as well as reduced ICAM-1 expression and inhibited NF-kappaB activity in the lungs.
Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Hormônio do Crescimento Humano/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Sepse/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/patologia , Animais , Hormônio do Crescimento Humano/genética , Hormônio do Crescimento Humano/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-10/sangue , Interleucina-10/imunologia , Pulmão/citologia , Pulmão/metabolismo , Pulmão/microbiologia , Pulmão/patologia , Camundongos , NF-kappa B/metabolismo , Distribuição Aleatória , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Sepse/imunologia , Sepse/microbiologia , Sepse/patologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/patogenicidade , Taxa de Sobrevida , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Mucosal tissue is the main portal of entry for HIV-1 infection and, in macaques, has been demonstrated to be a significant compartment for viral replication and CD4+ T lymphocyte depletion. Quantitating tissue viral burden in addition to plasma viral load provides insights into HIV-1 pathogenesis and an additional means to gauge antiretroviral response. The aim of this study was to develop reliable, reproducible, and sensitive assays to quantitate tissue viral burden of HIV-1 RNA and DNA using 1-3 endoscopically acquired, rectosigmoid biopsies. Total DNA and RNA were simultaneously extracted following homogenization from the same tissue samples. Quantitative polymerase chain reaction (PCR) assay in the HIV-1 LTR region was used to detect viral DNA and RT-PCR for viral RNA. It was determined that HIV-1 RNA and DNA can be reproducibly quantified from a single rectosigmoid biopsy with minimal intra-assay or intra-patient variability. These results reflect high recovery of extracted nucleic acids with calculated results accurately reflecting in vivo levels. The techniques outlined differ from currently available approaches by incorporating control standards to identify loss or degradation of RNA and DNA from acquisition through the in vitro assay and permit extraction with high yields of RNA and DNA from the same tissue sample.
Assuntos
DNA Viral/análise , Infecções por HIV/virologia , HIV-1/genética , Mucosa Intestinal/virologia , RNA Viral/análise , Carga Viral , Colonoscopia , Feminino , Infecções por HIV/patologia , HIV-1/fisiologia , Humanos , Mucosa Intestinal/patologia , Masculino , Reação em Cadeia da Polimerase/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Replicação ViralRESUMO
Nonhuman primate model systems of autologous CD34+ cell transplant are the most effective means to assess the safety and capabilities of lentivirus vectors. Toward this end, we tested the efficiency of marking, gene expression, and transplant of bone marrow and peripheral blood CD34+ cells using a self-inactivating lentivirus vector (CS-Rh-MLV-E) bearing an internal murine leukemia virus long terminal repeat derived from a murine retrovirus adapted to replicate in rhesus macaques. In vitro cytokine stimulation was not required to achieve efficient transduction of CD34+ cells resulting in marking and gene expression of the reporter gene encoding enhanced green fluorescent protein (EGFP) following transplant of the CD34+ cells. Monkeys transplanted with mobilized peripheral blood CD34+ cells resulted in EGFP expression in 1 to 10% of multilineage peripheral blood cells, including red blood cells and platelets, stable for 15 months to date. The relative level of gene expression utilizing this vector is 2- to 10-fold greater than that utilizing a non-self-inactivating lentivirus vector bearing the cytomegalovirus immediate-early promoter. In contrast, in animals transplanted with autologous bone marrow CD34+ cells, multilineage EGFP expression was evident initially but diminished over time. We further tested our lentivirus vector system by demonstrating gene transfer of the human common gamma-chain cytokine receptor gene (gamma(c)), deficient in X-linked SCID patients and recently successfully used to treat disease. Marking was 0.42 and.001 HIV-1 vector DNA copy per 100 cells in two animals. To date, all EGFP- and gamma(c)-transplanted animals are healthy. This system may prove useful for expression of therapeutic genes in human hematopoietic cells.
Assuntos
Citocinas/metabolismo , Técnicas de Transferência de Genes , Vetores Genéticos/genética , HIV-1/genética , Células-Tronco Hematopoéticas/metabolismo , Macaca mulatta/metabolismo , Receptores de Superfície Celular/genética , Animais , Antígenos CD34/metabolismo , Biomarcadores , Citometria de Fluxo , Expressão Gênica , Fator Estimulador de Colônias de Granulócitos/farmacologia , Proteínas de Fluorescência Verde , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucaférese , Proteínas Luminescentes , Linfócitos/metabolismo , Macaca mulatta/genética , Reação em Cadeia da Polimerase , Receptores de Superfície Celular/química , Receptores de Superfície Celular/metabolismo , Fator de Células-Tronco/farmacologia , Fatores de Tempo , Transdução GenéticaRESUMO
Recently, gene therapy vectors based upon the human immunodeficiency virus type 1 (HIV-1) genome have been developed. Here, we create an HIV-1 vector which is defective for all HIV-1 genes, but which maintains cis-acting elements required for efficient packaging, infection, and expression. In T cells transduced by this vector, vector expression is low but efficiently induced following HIV-1 infection. Remarkably, although the HIV-1 vector does not contain specific anti-HIV-1 therapeutic genes, the presence of the vector alone is sufficient to inhibit the spread of HIV-1 infection. The mechanism of inhibition is likely to be at the level of competition for limiting substrates required for either efficient packaging or reverse transcription, thereby selecting against propagation of wild-type HIV-1. These results provide proof of a concept for potential application of a novel HIV-1 vector in HIV-1 disease.
Assuntos
Vetores Genéticos , HIV-1/fisiologia , Replicação Viral , Linhagem Celular Transformada , Vetores Genéticos/genética , HIV-1/genética , Humanos , Transcrição Gênica , Células Tumorais Cultivadas , Montagem de VírusRESUMO
A retroviral vector containing human superoxide dismutase (SOD) cDNA was constructed and transfected into rat vascular smooth muscle cells (VSMCs). The expression of exogenous hSOD1 in the VSMCs was analyzed with Northern and Southern blot. The protection of the transfected and/or non-transfected VSMCs from free radical produced by the xanthine/xanthine oxidase (X/XO) system was investigated. The results showed that the construction strategy of the vector was correctly performed and the expression of hSOD1 in the transfected cells was highly detectable. The cell damage of X/XO could be alleviated with expression of hSOD1 in the transfected cells, as compared to control. In addition, proliferation of the transfected VSMCs resulted from oxidative stress was suppressed. It is suggested that the expression of gene-transferred hSOD1 is able to prevent the formation of atherosclerosis, partially due to its cell protection and inhibition of the proliferative embolization.
Assuntos
Músculo Liso Vascular/metabolismo , Superóxido Dismutase/biossíntese , Animais , Antioxidantes , Aorta Torácica , Divisão Celular , Células Cultivadas , Radicais Livres/metabolismo , Humanos , Músculo Liso Vascular/citologia , Ratos , Superóxido Dismutase/genética , TransfecçãoRESUMO
The recently developed CP/MAS 13C spectral editing technique is applied to the study of the structure of the dried Australian pine leaves. Subspectra of quaternary carbon C, methenyl CH, methylene CH2 and methyl CH3 for Australian pine leaves have been obtained. Simple formulae for spectral editing are proposed.
Assuntos
Interpretação Estatística de Dados , Espectroscopia de Ressonância Magnética/métodos , Folhas de Planta/química , Isótopos de Carbono , Dessecação , Poaceae/química , Especificidade da EspécieRESUMO
The chemokine receptor CXCR4 is the major coreceptor used for cellular entry by T cell- tropic human immunodeficiency virus (HIV)-1 strains, whereas CCR5 is used by macrophage (M)-tropic strains. Here we show that a small-molecule inhibitor, ALX40-4C, inhibits HIV-1 envelope (Env)-mediated membrane fusion and viral entry directly at the level of coreceptor use. ALX40-4C inhibited HIV-1 use of the coreceptor CXCR4 by T- and dual-tropic HIV-1 strains, whereas use of CCR5 by M- and dual-tropic strains was not inhibited. Dual-tropic viruses capable of using both CXCR4 and CCR5 were inhibited by ALX40-4C only when cells expressed CXCR4 alone. ALX40-4C blocked stromal-derived factor (SDF)-1alpha-mediated activation of CXCR4 and binding of the monoclonal antibody 12G5 to cells expressing CXCR4. Overlap of the ALX40-4C binding site with that of 12G5 and SDF implicates direct blocking of Env interactions, rather than downregulation of receptor, as the mechanism of inhibition. Thus, ALX40-4C represents a small-molecule inhibitor of HIV-1 infection that acts directly against a chemokine receptor at the level of Env-mediated membrane fusion.
Assuntos
Fármacos Anti-HIV/farmacologia , HIV-1/efeitos dos fármacos , HIV-1/metabolismo , Oligopeptídeos/farmacologia , Receptores CXCR4/antagonistas & inibidores , Infecções por HIV/imunologia , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , Humanos , Linfoma de Células T , Oligopeptídeos/metabolismo , Ligação Proteica/efeitos dos fármacos , Receptores CXCR4/metabolismo , Linfócitos T/virologia , Células Tumorais CultivadasRESUMO
A full-length cDNA for cysteine-rich venom protein (CRVP) was constructed by immunoscreening and 5'-rapid amplification of cDNA ends from a cDNA library of venom gland of Trimeresurus mucrosquamatus. The predicted CRVP consisted of 183 amino acid residues including a putative signal peptide of 21 residues. Northern blot hybridization suggested the tissue-specific expression in venom gland and its corresponding length of cDNA. The predicted amino acid sequence of CRVP was homologous to a rat epididymal metalloprotein and a lizard helothermine. Amino acid sequence analysis suggested that CRVP may be a venom metalloprotein targeted against ryanodine receptors and Ca2+ release. Moreover, CRVP expressed in Escherichia coli exhibited the same antigenicity as their native venom forms of T. mucrosquamatus. This is the first report in the cloning and expression of a CRVP from the venom gland of T. mucrosquamatus.
Assuntos
Venenos de Crotalídeos/química , Venenos de Crotalídeos/isolamento & purificação , Vetores Genéticos , Neurotoxinas , Proteínas/isolamento & purificação , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , Sequência Consenso , DNA Complementar/isolamento & purificação , Escherichia coli , Código Genético , Lagartos , Dados de Sequência Molecular , Ratos , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas de Répteis , Homologia de Sequência de Aminoácidos , Transcrição GênicaRESUMO
OBJECTIVE: To observe the effect of Liangxue Piyan granule No. 2 (LPG) on psoriasis. METHODS: Ninety-six cases of psoriasis patients were treated with LPG and a control group of 32 cases was set up, which was treated with Fufang Qingdai Capsule (FQC). RESULTS: The total effective rate of LPG was 84.7%, that of the control group was 71.9% (P > 0.05), there was no significant difference between two drugs in treatment of psoriasis. The recurrent rate of LPG group (3.6%) was lower than that of control (21.7%), P < 0.01. CONCLUSION: This granule provides a better drug for treatment of psoriasis.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Psoríase/tratamento farmacológico , Adolescente , Adulto , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Criança , Feminino , Humanos , Interleucina-6/sangue , Queratinócitos/citologia , Masculino , Pessoa de Meia-Idade , Psoríase/sangue , RecidivaRESUMO
An oligocationic peptide compound (ALX40-4C) was developed for consideration in the treatment of human immunodeficiency virus type 1 (HIV-1) infection. This compound was designed to mimic the basic domain of the HIV-1 transactivation protein, Tat, and will competitively inhibit Tat binding to its specific RNA hairpin target (TAR [transactivation region]), found at the 5' end of all HIV-1 transcripts. Blocking Tat-TAR interactions can abrogate HIV-1 replication. ALX40-4C was shown to inhibit replication of HIV-1NL4-3 in a range of cell types, including primary cells and transformed cell lines, by as much as 10(4)-fold. In some experiments, virus rescue was not possible even after removal of ALX40-4C from the cultures. Strain-dependent resistance has been demonstrated for all antiretroviral agents tested; therefore, we tested for variable sensitivity to ALX40-4C. The cloned primary strains, HIV-JR-CSF and HIV-JR-FL, were less sensitive to ALX40-4C inhibition. Unexpectedly, determinants for efficient ALX40-4C inhibition were mapped by using recombinant virus strains to the V3 region of gpl20 and were shown to act at early events in viral replication, which include viral entry. If entry and reverse transcription are bypassed by transfection, a more modest, virus strain-independent inhibition is shown; this inhibition is likely due to blocking of Tat-TAR interaction. Thus, the highly basic oligocationic Tat inhibitor ALX40-4C appears to interfere with initial virus-target cell interactions which involve HIV-1 gp120 V3 determinants, most efficiently for T-cell line-adapted strains.
Assuntos
Antivirais/farmacologia , Proteína gp120 do Envelope de HIV/efeitos dos fármacos , HIV-1/efeitos dos fármacos , Oligopeptídeos/farmacologia , Replicação Viral/efeitos dos fármacos , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Clonagem Molecular , Resistência Microbiana a Medicamentos , Produtos do Gene tat/antagonistas & inibidores , Produtos do Gene tat/metabolismo , Proteína gp120 do Envelope de HIV/metabolismo , Repetição Terminal Longa de HIV , HIV-1/isolamento & purificação , HIV-1/fisiologia , Humanos , Cinética , Testes de Sensibilidade Microbiana , Provírus/efeitos dos fármacos , Provírus/fisiologia , Mapeamento por Restrição , Ativação Transcricional/efeitos dos fármacos , Produtos do Gene tat do Vírus da Imunodeficiência HumanaRESUMO
Despite considerable evidence that cell activation enhances human immunodeficiency virus-type 1 (HIV-1) replication in vitro, there is very little data on the role of immune activation on in vivo HIV-1 replication. In this study, we examined the effect of influenza vaccination on HIV-1 replication in the peripheral blood of 20 study subjects, and in 14 control subjects who did not receive influenza vaccination. Blood was obtained from each subject on three occasions during the month before vaccination and again on three occasions during the following month. Over the study period, there was little change in levels of proviral DNA in peripheral blood mononuclear cells (PBMCs). However, peak PBMC viral RNA levels after influenza vaccination were significantly increased over the mean of prevaccination values. This change was not observed to the same extent in unvaccinated controls. Therefore, this is the first report showing that HIV-1 replication can increase in temporal association with influenza vaccination. Our results suggest that continued immunologic (antigenic) stimulation may result in increased virus load in vivo. To address the appropriateness of influenza vaccination in HIV-infected patients, expanded studies will be required to examine specific and generalized immune responses to vaccination, and differences in patient response based on disease stage.