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1.
Nutr. hosp ; 40(4): 839-847, Juli-Agos. 2023. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-224209

RESUMO

Background: immunonutrition has been introduced and proposed to have positive modulating effects on inflammatory and immune responses in surgical patients. This meta-analysis aimed to assess whether perioperative enteral immunonutrition (EIN) can reduce postoperative complications or reduce inflammatory responses in esophageal cancer (EC) patients undergoing esophagectomy. Methods: PubMed, Embase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of EIN before and/or after surgery in EC patients undergoing esophagectomy were identified. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. Results: ten RCTs involving 1,052 patients were included in the meta-analysis, including 573 patients in the EIN group and 479 patients in the enteral nutrition (EN) group. Overall, no significant difference was observed between the two groups in the incidence of postoperative pneumonia, surgical site infection, intra-abdominal abscess, septicemia, and urinary tract infection. No significant incidence of postoperative anastomotic leakage, acute respiratory distress syndrome (ARDS), and in-hospital mortality was found. Conclusions: perioperative enteral immunonutrition did not reduce the incidence of infectious complications and anastomotic leakage in EC patients undergoing esophagectomy, nor did it reduce postoperative CRP and IL-6, but did not increase in-hospital mortality.(AU)


Antecedentes: se ha introducido y propuesto la inmunonutrición para regular activamente la inflamación y la respuesta inmune en pacientesquirúrgicos. El presente metaanálisis fue diseñado para evaluar si la inmunonutrición enteral perioperatoria (EIN, por sus siglas en inglés) puedereducir las complicaciones postoperatorias o la inflamación en pacientes con cáncer de esófago (CE) sometidos a esofagectomía.Métodos: se realizó una búsqueda sistemática en las bases de datos de PubMed, Embase, Web of Science, EBSCO y Cochrane Library. Se evaluóel efecto de la EIN preoperatoria y/o postoperatoria en un ensayo aleatorizado controlado (RCT) en pacientes con cáncer de esófago sometidosa esofagectomía. Dos investigadores buscaron independientemente artículos, extrajeron datos y evaluaron la calidad de los artículos incluidos.Resultados: el metanálisis incluyó diez ensayos controlados aleatorios en los que participaron 1.052 pacientes, de los cuales 573 fueronincluidos en el grupo EIN y 479, en el grupo de nutrición enteral (NE). En general, no hubo diferencia significativa en la incidencia de neumoníapostoperatoria, infección del sitio quirúrgico, absceso intraperitoneal, sepsis e infección del tracto urinario entre los dos grupos. No hubo diferenciasignificativa en la incidencia de fístula anastomótica postoperatoria, síndrome de distrés respiratorio agudo (SDRA) y mortalidad hospitalaria.Conclusión: la inmunonutrición enteral perioperatoria no puede reducir la incidencia de complicaciones infecciosas postoperatorias y fístulasanastomóticas, ni la PCR postoperatoria ni la IL-6. Pero no aumentó la mortalidad hospitalaria.(AU)


Assuntos
Humanos , Masculino , Feminino , Esofagectomia , Complicações Pós-Operatórias , Nutrição Enteral , Neoplasias Esofágicas/dietoterapia , 52503 , 24439
2.
Nutr Hosp ; 40(4): 839-847, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37073747

RESUMO

Introduction: Background: immunonutrition has been introduced and proposed to have positive modulating effects on inflammatory and immune responses in surgical patients. This meta-analysis aimed to assess whether perioperative enteral immunonutrition (EIN) can reduce postoperative complications or reduce inflammatory responses in esophageal cancer (EC) patients undergoing esophagectomy. Methods: PubMed, Embase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of EIN before and/or after surgery in EC patients undergoing esophagectomy were identified. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. Results: ten RCTs involving 1,052 patients were included in the meta-analysis, including 573 patients in the EIN group and 479 patients in the enteral nutrition (EN) group. Overall, no significant difference was observed between the two groups in the incidence of postoperative pneumonia, surgical site infection, intra-abdominal abscess, septicemia, and urinary tract infection. No significant incidence of postoperative anastomotic leakage, acute respiratory distress syndrome (ARDS), and in-hospital mortality was found. Conclusions: perioperative enteral immunonutrition did not reduce the incidence of infectious complications and anastomotic leakage in EC patients undergoing esophagectomy, nor did it reduce postoperative CRP and IL-6, but did not increase in-hospital mortality.


Introducción: Antecedentes: se ha introducido y propuesto la inmunonutrición para regular activamente la inflamación y la respuesta inmune en pacientes quirúrgicos. El presente metaanálisis fue diseñado para evaluar si la inmunonutrición enteral perioperatoria (EIN, por sus siglas en inglés) puede reducir las complicaciones postoperatorias o la inflamación en pacientes con cáncer de esófago (CE) sometidos a esofagectomía. Métodos: se realizó una búsqueda sistemática en las bases de datos de PubMed, Embase, Web of Science, EBSCO y Cochrane Library. Se evaluó el efecto de la EIN preoperatoria y/o postoperatoria en un ensayo aleatorizado controlado (RCT) en pacientes con cáncer de esófago sometidos a esofagectomía. Dos investigadores buscaron independientemente artículos, extrajeron datos y evaluaron la calidad de los artículos incluidos. Resultados: el metanálisis incluyó diez ensayos controlados aleatorios en los que participaron 1.052 pacientes, de los cuales 573 fueron incluidos en el grupo EIN y 479, en el grupo de nutrición enteral (NE). En general, no hubo diferencia significativa en la incidencia de neumonía postoperatoria, infección del sitio quirúrgico, absceso intraperitoneal, sepsis e infección del tracto urinario entre los dos grupos. No hubo diferencia significativa en la incidencia de fístula anastomótica postoperatoria, síndrome de distrés respiratorio agudo (SDRA) y mortalidad hospitalaria. Conclusión: la inmunonutrición enteral perioperatoria no puede reducir la incidencia de complicaciones infecciosas postoperatorias y fístulas anastomóticas, ni la PCR postoperatoria ni la IL-6. Pero no aumentó la mortalidad hospitalaria.


Assuntos
Neoplasias Esofágicas , Esofagectomia , Humanos , Esofagectomia/efeitos adversos , Fístula Anastomótica , Dieta de Imunonutrição , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Neoplasias Esofágicas/cirurgia
3.
Dis Markers ; 2022: 2431976, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35789606

RESUMO

Rheumatoid arthritis (RA) is a chronic systematicness autoimmunity disease with joint inflammation. RA etiology is still unknown. Early and exact diagnosing is still hard to reach. In the paper, we purposed to discover novel diagnosis biological marker for RA. Two open, usable gene expression profiles of human RA as well as controlled specimens (dataset GSE17755 as well as GSE93272) were downloaded from the GEO database. Differentially expressed genes (DEGs) were screened between 331 RA and 88 control samples. Functional enrichment analysis was applied to explore the possible function of DEGs. Expression levels as well as diagnosis values of biological marker in RA were further verified in our cohort by the use of RT-PCR and ROC assays. We identified 13 DEGs between RA samples and control samples. 13 DEGs were remarkably abundant in NF-kappa B signal pathway. Among the 13 DEGs, CKS2, S100A12, LY96, and ANXA3 exhibited a strong diagnostic ability in screening RA specimens from normal specimens using all AUC > 0.8. Moreover, we confirmed that the expression of CKS2 and S100A12 was distinctly upregulated in RA specimens contrasted to normal specimens. Overall, serum CKS2 and S100A12 could be used as novel diagnosis biological markers for RA patients.


Assuntos
Artrite Reumatoide , Quinases relacionadas a CDC2 e CDC28 , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Biomarcadores/metabolismo , Quinases relacionadas a CDC2 e CDC28/genética , Proteínas de Ciclo Celular/genética , Perfilação da Expressão Gênica , Humanos , Proteína S100A12/genética , Transcriptoma
4.
World J Clin Cases ; 10(1): 35-42, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35071503

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is a prevalent clinical autoimmune disease that is commonly treated with diclofenac and methotrexate. In recent years, the application of traditional Chinese medicine in RA has received widespread attention; it promotes blood circulation, strengthens the immune system, and eliminates evil. The sinomenine preparation of Zhingqeng Fengtongning is studied as a possible treatment for patients with RA. AIM: To explore the value of sinomenine injection into the articular cavity for the treatment of RA. METHODS: A total of 94 patients with RA treated from January 2019 to January 2021 were selected and divided into the study and control groups with 47 patients each using a simple random number table method. Both groups received conventional treatment with diclofenac sodium and methotrexate tablets. The control group received diproxone and lidocaine by intra-articular administration while the study group received an intra-articular administration of the sinomenine preparation of Zhengqing Fengning and lidocaine. χ 2 test was used to evaluate the therapeutic effect and synovial thickness, degree of pain through the visual analog scale (VAS), blood flow grade, arthroinflammatory indexes [rheumatoid factor (RF), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR)] before and after treatment in the two groups. RESULTS: The total effective rate of the study group (93.62%) was higher than that of the control group (78.72%) (P < 0.05). Before treatment, there were no significant differences between the two groups in terms of synovial thickness, VAS score, blood flow grading, levels of RF, and ESR (P > 0.05). After treatment, the synovial thickness and VAS score were significantly lower (P < 0.05) in the study group than in the control group (2.05 ± 0.59 mm vs 2.87 ± 0.64 mm and 2.11 ± 0.62 vs 2.90 ± 0.79 scores, respectively). The rate of blood flow at grade 0 in the study group (76.60%) was higher than that in the control group (57.45%), and the rate of blood flow at grade I (10.64%) was lower than that in the control group (31.91%) (P < 0.05). Furthermore, the levels of RF (55.61 ± 6.13 U/mL), CRP (11.43 ± 3.59 mg/L), and ESR (29.60 ± 5.56 mm/h) in the study group were lower than those in the control group (73.04 ± 9.23 U/mL, 15.07 ± 4.06 mg/L, 36.64 ± 6.10 mm/h, respectively) (P < 0.05). CONCLUSION: Sinomenine administration of Zhengqing Fengtongning in the articular cavity with conventional treatment of RA can improve ultrasonographic blood flow and synovial thickness, reduce pain, regulate inflammation, and enhance therapeutic effect.

5.
J Affect Disord ; 278: 311-319, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32979562

RESUMO

BACKGROUND: The microbiome-gut-brain axis, especially the microbial tryptophan biosynthesis and metabolism pathway (MiTBamp), is closely connected to bipolar disorder with current major depressive episode (BPD). METHODS: We performed shotgun metagenomics sequencing (SMS) of faecal samples from 25 BPD patients and 28 healthy controls (HCs). Except for the microbiota taxa and MiTBamp analyses, we also built a classification model using the Random Forests (RF) and Boruta algorithm to find the microbial biomarkers for BPD. RESULTS: Compared to HCs, the phylum Bacteroidetes abundance was significantly reduced, whereas that of the Actinobacteria and Firmicutes were significantly increased in BPD patients. We also identified 38 species increased and 6 species decreased significantly in the BPD group. In the MiTBamp, we identified that two Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K00658 and K00837) were significantly lower in the BPD, and five KOs (K01696, K00382, K00626, K01667, and K03781) were significantly higher in the BPD group. We also identified significant genera and species which were closely related to these KOs. Finally, RF classification based on gut microbiota at the genus level can achieve an area under the receiver operating characteristic curve of 0.997. LIMITATIONS: The features of cross-sectional design, limited sample size, the heterogeneity of bipolar disorders, and a lack of serum/plasma tryptophan concentration measurements. CONCLUSIONS: The present findings enable a better understanding of changes in gastrointestinal microbiome and MiTBamp in BPD. Alterations of microbes may have potential as biomarkers for distinguishing the BPD patients form HCs.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Microbioma Gastrointestinal , Transtorno Bipolar/genética , Estudos Transversais , Transtorno Depressivo Maior/genética , Microbioma Gastrointestinal/genética , Humanos , Metagenômica , Triptofano
6.
Pharmaceutics ; 12(12)2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33321797

RESUMO

Tuberculosis (TB) is a contagious airborne disease caused by Mycobacterium tuberculosis, which primarily affects human lungs. The progression of drug-susceptible TB to drug-resistant strains, MDR-TB and XDR-TB, has become worldwide challenge in eliminating TB. The limitations of conventional TB treatment including frequent dosing and prolonged treatment, which results in patient's noncompliance to the treatment because of treatment-related adverse effects. The non-invasive pulmonary drug administration provides the advantages of targeted-site delivery and avoids first-pass metabolism, which reduced the dose requirement and systemic adverse effects of the therapeutics. With the modification of the drugs with advanced carriers, the formulations may possess sustained released property, which helps in reducing the dosing frequency and enhanced patients' compliances. The dry powder inhaler formulation is easy to handle and storage as it is relatively stable compared to liquids and suspension. This review mainly highlights the aerosolization properties of dry powder inhalable formulations with different anti-TB agents to understand and estimate the deposition manner of the drug in the lungs. Moreover, the safety profile of the novel dry powder inhaler formulations has been discussed. The results of the studies demonstrated that dry powder inhaler formulation has the potential in enhancing treatment efficacy.

7.
Mol Ther Methods Clin Dev ; 19: 149-161, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33102612

RESUMO

Emerging base editing technology exploits CRISPR RNA-guided DNA modification effects for highly specific C > T conversion, which has been used to efficiently disrupt gene expression. These tools can enhance synthetic T cell immunity by restricting specificity, addressing histocompatibility leukocyte antigen (HLA) barriers, and promoting persistence. We report lentiviral delivery of a hepatitis B-virus (HBV)-specific recombinant T cell receptor (rTCR) and a linked CRISPR single-guide RNA for simultaneous disruption of endogenous TCRs (eTCRs) when combined with transient cytosine deamination. Discriminatory depletion of eTCR and coupled expression of rTCR resulted in enrichment of HBV-specific populations from 55% (SEM, ±2.4%) to 95% (SEM, ±0.5%). Intensity of rTCR expression increased 1.8- to 2.9-fold compared to that in cells retaining their competing eTCR, and increased cytokine production and killing of HBV antigen-expressing hepatoma cells in a 3D microfluidic model were exhibited. Molecular signatures confirmed that seamless conversion of C > T (G > A) had created a premature stop codon in TCR beta constant 1/2 loci, with no notable activity at predicted off-target sites. Thus, targeted disruption of eTCR by cytosine deamination and discriminatory enrichment of antigen-specific T cells offers the prospect of enhanced, more specific T cell therapies against HBV-associated hepatocellular carcinoma (HCC) as well as other viral and tumor antigens.

8.
Eur J Med Chem ; 119: 231-49, 2016 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-27173385

RESUMO

Malaria remains a significant infectious disease with even artemisinin-based therapies now facing resistance in the field. Development of new therapies is urgently needed, either by finding new compounds with unique modes of action, or by reversing resistance towards known drugs with 'chemosensitizers' or 'chemoreversal' agents (CRA). Concerning the latter, we have focused on the resistance mechanisms developed against chloroquine (CQ). We have synthesized a series of compounds related to previously identified CRAs, and found promising novel compounds. These compounds show encouraging results in a coumarin labeled chloroquine uptake assay, exhibiting a dose response in resensitising parasites to the antimalarial effects of chloroquine. Selected compounds show consistent potency across a panel of chloroquine and artemisinin sensitive and resistant parasites, and a wide therapeutic window. This data supports further study of CRAs in the treatment of malaria and, ultimately, their use in chloroquine-based combination therapies.


Assuntos
Antimaláricos/síntese química , Antimaláricos/farmacologia , Cloroquina/farmacologia , Desenho de Fármacos , Resistência a Medicamentos/efeitos dos fármacos , Animais , Antimaláricos/química , Antimaláricos/metabolismo , Transporte Biológico , Linhagem Celular , Técnicas de Química Sintética , Relação Dose-Resposta a Droga , Concentração Inibidora 50 , Camundongos , Modelos Moleculares , Conformação Molecular , Plasmodium falciparum/efeitos dos fármacos , Relação Estrutura-Atividade
9.
Antimicrob Agents Chemother ; 60(5): 3076-89, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26953199

RESUMO

Resistance to antimalarial therapies, including artemisinin, has emerged as a significant challenge. Reversal of acquired resistance can be achieved using agents that resensitize resistant parasites to a previously efficacious therapy. Building on our initial work describing novel chemoreversal agents (CRAs) that resensitize resistant parasites to chloroquine (CQ), we herein report new hybrid single agents as an innovative strategy in the battle against resistant malaria. Synthetically linking a CRA scaffold to chloroquine produces hybrid compounds with restored potency toward a range of resistant malaria parasites. A preferred compound, compound 35, showed broad activity and good potency against seven strains resistant to chloroquine and artemisinin. Assessment of aqueous solubility, membrane permeability, and in vitro toxicity in a hepatocyte line and a cardiomyocyte line indicates that compound 35 has a good therapeutic window and favorable drug-like properties. This study provides initial support for CQ-CRA hybrid compounds as a potential treatment for resistant malaria.


Assuntos
Antimaláricos/química , Antimaláricos/farmacologia , Cloroquina/química , Cloroquina/farmacologia , Artemisininas/química , Artemisininas/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Relação Estrutura-Atividade
10.
Am J Clin Oncol ; 38(3): 322-5, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23934134

RESUMO

Gemcitabine (GEM) is an approved treatment for unresectable pancreatic cancer; however, its role in treating resected pancreatic cancer is less clear. The aim of this study was to investigate the evidence of the role of adjuvant GEM therapy on survival in resected pancreatic cancer. Four phase III randomized trials of adjuvant GEM in patients with resected pancreatic cancer were identified and the hazard ratio (HR) for overall survival were used in this meta-analysis; 2 studies compared GEM treatment with best supportive care and 2 studies with 5-fluorouracil/folinic acid therapy. The pooled data (n=2017 patients) indicated that the overall survival data were homogenous among the studies (Q=4.371; I=31.37%; P=0. 224). The combined HR significantly favors GEM over the other treatments. The overall HR was 0.88 (range, 0. 720 to 0.940; P=0.014). The results indicate that GEM prolongs overall survival compared with other treatments after the resection of pancreatic cancer.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/terapia , Quimioterapia Adjuvante , Desoxicitidina/uso terapêutico , Humanos , Pancreatectomia , Taxa de Sobrevida , Gencitabina
11.
Chin Med J (Engl) ; 125(8): 1389-92, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22613640

RESUMO

BACKGROUND: As a new electroencephalogram (EEG) signal processing technique for monitoring the depth of anesthesia, entropy consists of two indices: reaction entropy (RE) and state entropy (SE). Our study compared entropy with classical bispectral index (BIS) in reduction of myoelectrical interference and noxious stimuli with EEG signals. METHODS: Two hundred and eighty patients (ASA I-II, 18-60 years old) undergoing scheduled surgeries from seven medical centers were enrolled. Anesthesia induction was managed with propofol via the target-controlled infusion (TCI) system. The results of BIS, RE, SE, mean arterial pressure (MAP) and heart rate (HR) were recorded before anesthesia induction, at the moment of unconsciousness, before and 2 minutes after administration of muscle relaxant, and before and one and three minutes after the tracheal intubation. RESULTS: The values of half maximum effective concentrations (EC50), 5% effective concentrations (EC05) and 95% effective concentrations (EC95) of propofol effect-site concentration at the onset of unconsciousness were 1.2 (1.1-1.3 µg/ml), 2.5 (2.4-2.5 µg/ml) and 3.7 (3.7-3.8 µg/ml), while those of the predicted plasma propofol concentration were 2.8 (2.7-2.9 µg/ml), 3.9 (3.8-3.9 µg/ml) and 4.9 (4.8-5.0 µg/ml), respectively. The values of BIS, SE and RE were 62, 59 and 63 when 50% of patients lost consciousness, and 79, 80, 85 and 42, 37, 44, respectively, when 5% and 95% of patients were unconscious. The values of BIS, RE and SE dropped two minutes after the injection of muscle relaxant, but there were no significant differences between RE and SE. MAP and HR increased visibly, which indicated a reaction to tracheal intubation; the values of BIS, RE and SE, however, did not display any significant changes. CONCLUSIONS: This large-sample multicentric study confirmed the values of RE and SE as approximating BIS value, at the onset of unconsciousness during propofol TCI anesthesia. After elimination of myoelectrical activation, all values of RE, SE and BIS decreased significantly and the three indices were less sensitive to noxious stimuli than cardiovascular responses.


Assuntos
Anestesia , Anestésicos Intravenosos/farmacologia , Eletroencefalografia , Entropia , Propofol/farmacologia , Adulto , Pressão Sanguínea , Eletromiografia , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Propofol/sangue
12.
Med Hypotheses ; 77(2): 246-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21555187

RESUMO

Amnesia is a fundamental component of a proper general anesthetic. The mechanism of anesthetic-induced amnesia remains poorly understood. Nowadays, intraoperative awareness and postoperative cognitive dysfunction are two distressing problems receiving increased attention by clinicians, patients and the general public. Extensive evidence indicates that general anesthetics cause amnesia by working on hippocampus and basolateral amygdala (BLA). Recently, evidence from studies in experimental animals has shown that either intra-hippocampus or intra-BLA injection of endogenous cannabinoid receptor 1 (CB1) drugs result in significant changes of cognitive function. In addition, several general anesthetics (i.e. propofol, etomidate and isoflurane) have been reported to interact with the endocannabinoid system. However, there are few studies about whether the CB1 receptor system is involved in anesthetic-induced amnesia. We hypothesize that the CB1 receptor activity in hippocampus and BLA might be regulated by general anesthetics. Once the involvement of the endocannabinoid system in anesthetic-induced amnesia is proved, it will provide a new way to prevent and treat post-traumatic stress disorder caused by intraoperative awareness and postoperative cognitive dysfunction in the future.


Assuntos
Amnésia/induzido quimicamente , Tonsila do Cerebelo/metabolismo , Anestésicos Gerais/efeitos adversos , Moduladores de Receptores de Canabinoides/fisiologia , Endocanabinoides , Hipocampo/metabolismo , Modelos Neurológicos , Receptor CB1 de Canabinoide/metabolismo , Anestésicos Gerais/metabolismo , Moduladores de Receptores de Canabinoides/metabolismo , Humanos
13.
Neurosci Lett ; 496(3): 163-7, 2011 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-21514363

RESUMO

In prior studies, Eph/ephrin system was demonstrated to be involved in inflammatory and neuropathic pain modulation. The present study was to investigate whether the spinal Eph/ephrin signaling was involved in modulation of spinal inflammatory cytokines in bone cancer pain (BCP) of rats. BCP was induced by intra-tibial inoculation of Walker 256 mammary gland carcinoma cells. The expressions of EphB1/ephrinB1 in spinal cord (SC) and dorsal root ganglia (DRG) were determined. At 16 days post inoculation, the pain relieving effect and the mRNA levels of inflammatory cytokines were detected after intrathecal administration of EphB1-Fc (blocker of EphB1 receptor, 10µg). The results showed that the EphB1/ephrinB1 expression was significantly increased in SC, but ephrinB1 was decreased in DRG after Walker 256 inoculation. The mechanical allodynia induced by bone cancer was significantly alleviated by intrathecal administration of EphB1-Fc. Furthermore, the RT-PCR analysis showed that the mRNA levels of IL-1ß, IL-6 and TNF-α were significantly increased at 16 days post Walker 256 inoculation and were significantly suppressed by intrathecal administration of EphB1-Fc in SC. We concluded that Eph/ephrin might be involved in the maintenance of mechanical allodynia, via modulating the expression of spinal inflammatory cytokines, in the present rat model of BCP. This study suggested that Eph/ephrin signaling would be a potential target for the treatment of BCP.


Assuntos
Neoplasias Ósseas/complicações , Dor/etiologia , Dor/fisiopatologia , Receptor EphB1/fisiologia , Animais , Carcinoma 256 de Walker/metabolismo , Carcinoma 256 de Walker/fisiopatologia , Citocinas/biossíntese , Feminino , Gânglios Espinais/metabolismo , Imuno-Histoquímica , Injeções Espinhais , Interleucina-1beta/biossíntese , Interleucina-6/biossíntese , Transplante de Neoplasias , Medição da Dor/efeitos dos fármacos , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Wistar , Receptor EphB1/antagonistas & inibidores , Receptor EphB1/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia , Fator de Necrose Tumoral alfa/biossíntese
14.
Chin Med J (Engl) ; 123(12): 1553-6, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20819511

RESUMO

BACKGROUND: Oxidative stress and inflammation are important steps in the pathogenesis of atherosclerosis. We postulated that therapeutic concentrations of aspirin and pravastatin, especially in combination, may suppress oxidative stress and inflammation in endothelial cells, and this concept was examined in human coronary artery endothelial cells (HCAECs). METHODS: Human coronary artery endothelial cells were cultured and treated with oxidized-low density lipoprotein (ox-LDL, 60 microg/ml for 24 hours) alone, or pre-treated with aspirin (1, 2 or 5 mmol/L), pravastatin (1, 5 or 10 micromol/L) or their combination (1 mmol/L aspirin and 5 micromol/L pravastatin), followed by ox-LDL treatment. After respective treatment, superoxide anion production, p38 mitogen activated protein kinase and transcription factor NF-kappaB activation, protein expression of lectin-like ox-LDL receptor-1 (LOX-1) and adhesion molecules, and monocyte adhesion were measured. RESULTS: Ox-LDL treatment greatly elicited its receptor LOX-1 expression, superoxide anion production and inflammatory response, which were minimally affected by low concentration of aspirin (1 mmol/L) or pravastatin (5 micromol/L), but were markedly decreased by their combination. Activation of p38 mitogen activated protein kinase and NF-kappaB, the expression of intercellular adhesion molecule-1 and monocyte chemotactic protein-1, which were only mildly affected by aspirin or pravastatin alone, were significantly attenuated by their combination. As a consequence, monocyte adhesion to endothelial cells was markedly attenuated by the combination of the two agents. Well-known anti-oxidants alpha-tocopherol and gamma-tocopherol had similar inhibitory effects on ox-LDL-mediated oxidative stress and LOX-1 expression as well as monocyte adhesion as did the combination of aspirin and pravastatin. CONCLUSIONS: These studies point to a positive interaction between aspirin and pravastatin with regard to endothelial biology. Anti-oxidant and subsequent anti-inflammatory effect may be one of the potential underling mechanisms.


Assuntos
Aspirina/farmacologia , Moléculas de Adesão Celular/metabolismo , Células Endoteliais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Pravastatina/farmacologia , Receptores Depuradores Classe E/metabolismo , Anticolesterolemiantes/farmacologia , Western Blotting , Células Cultivadas , Vasos Coronários/citologia , Inibidores de Ciclo-Oxigenase/farmacologia , Ensaio de Desvio de Mobilidade Eletroforética , Células Endoteliais/metabolismo , Humanos , Superóxidos/metabolismo
15.
Nan Fang Yi Ke Da Xue Xue Bao ; 28(7): 1247-8, 2008 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-18676275

RESUMO

OBJECTIVE: To evaluate the therapeutic effect of preoperative regional intra-arterial chemotherapy (PRAC) on progressive lower rectal cancer. METHODS: Forty-five patients with progressive lower rectal cancer were divided into groups A (23 cases) and B (22 cases) for treatment with PRAC 1 to 2 weeks prior to surgical tumor resection or with surgical resection only, respectively. RESULTS: PRAC caused obvious tissue degeneration and necrosis of rectal cancer with a total effective rate of 95.65%. The rates of radical resection in groups A and B were 91.3% and 72.27%, respectively. The 1-year postoperative survival rates of the two groups were 95.65% and 86.36%, with 3-year survival of 89.96% and 68.18%, and 3-year postoperative recurrence rates of 8.69% and 27.27%, respectively. The anal preservation rates of the two groups were 78.26% and 59.09%. CONCLUSION: PRAC can increase radical resection rates, promote the postoperative survival and anal preservation rate, and lower the recurrence rate in patients with lower rectal cancer.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioterapia Adjuvante , Feminino , Humanos , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Neoplasias Retais/mortalidade , Neoplasias Retais/cirurgia , Taxa de Sobrevida
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