RESUMO
PURPOSE: To compare the efficacy and safety of high-dose vitamin C plus FOLFOX ± bevacizumab versus FOLFOX ± bevacizumab as first-line treatment in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Between 2017 and 2019, histologically confirmed patients with mCRC (n = 442) with normal glucose-6-phosphate dehydrogenase status and no prior treatment for metastatic disease were randomized (1:1) into a control (FOLFOX ± bevacizumab) and an experimental [high-dose vitamin C (1.5 g/kg/d, intravenously for 3 hours from D1 to D3) plus FOLFOX ± bevacizumab] group. Randomization was based on the primary tumor location and bevacizumab prescription. RESULTS: The progression-free survival (PFS) of the experimental group was not superior to the control group [median PFS, 8.6 vs. 8.3 months; HR, 0.86; 95% confidence interval (CI), 0.70-1.05; P = 0.1]. The objective response rate (ORR) and overall survival (OS) of the experimental and control groups were similar (ORR, 44.3% vs. 42.1%; P = 0.9; median OS, 20.7 vs. 19.7 months; P = 0.7). Grade 3 or higher treatment-related adverse events occurred in 33.5% and 30.3% of patients in the experimental and control groups, respectively. In prespecified subgroup analyses, patients with RAS mutation had significantly longer PFS (median PFS, 9.2 vs. 7.8 months; HR, 0.67; 95% CI, 0.50-0.91; P = 0.01) with vitamin C added to chemotherapy than with chemotherapy only. CONCLUSIONS: High-dose vitamin C plus chemotherapy failed to show superior PFS compared with chemotherapy in patients with mCRC as first-line treatment but may be beneficial in patients with mCRC harboring RAS mutation.
Assuntos
Antineoplásicos , Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ácido Ascórbico/efeitos adversos , Bevacizumab , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Fluoruracila , Glucosefosfato Desidrogenase/uso terapêutico , Humanos , Leucovorina , Neoplasias Retais/etiologiaRESUMO
OBJECTIVE: Donor-derived carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has recently emerged as a critical early complication after renal transplantation. Although CRKP is usually sensitive to tigecycline, monotherapy with this drug is often less than effective. We investigated the efficacy of a combined regimen of tigecycline with high-dose, extended-infusion meropenem in the treatment of donor-derived CRKP infection after kidney transplantation. METHODS: From Jan. 2016 to Dec. 2017, a total of 12 CRKP isolates were detected from cultures of the organ preservation solution used for soaking the donor kidneys at our institute. Probable or possible donor-derived infection (DDI) was identified in 8 transplant recipients. Clinical data were retrospectively analyzed. RESULTS: Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing CRKP was reported to be positive in organ preservation solution cultures at 3.5±0.9 days after transplantation, leading to surgical site (n=3), urinary tract (n=4), and/or bloodstream (n=2) infections in 8 recipients. The drug susceptibility tests showed that CRKP was sensitive to tigecycline, but resistant to meropenem. In 7 patients who received tigecycline combined with high-dose extended-infusion meropenem, DDIs were successfully cured. The length of hospital stay was 31 (18-129) days, and the serum creatinine at discharge was 105.8±16.7 µmol/L. The one remaining patient who received tigecycline combined with intravenous-drip meropenem died of septic shock. A median follow-up of 43 months (33-55) showed no recurrence of new CRKP infection in the 7 surviving recipients. CONCLUSION: It was suggested that a prompt and appropriate combination therapy using tigecycline with high-dose extended-infusion meropenem is effective in treating donor-derived KPC-2-producing CRKP infection after renal transplantation.
Assuntos
Proteínas de Bactérias/genética , Infecções por Klebsiella/tratamento farmacológico , Meropeném/farmacologia , Tigeciclina/farmacologia , beta-Lactamases/genética , Adolescente , Adulto , Carbapenêmicos/efeitos adversos , Carbapenêmicos/farmacologia , Criança , Farmacorresistência Bacteriana/genética , Feminino , Humanos , Lactente , Transplante de Rim/efeitos adversos , Infecções por Klebsiella/etiologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/patogenicidade , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Doadores de Tecidos , Adulto JovemRESUMO
Muehlenbeckia volcanica (Benth.) Endl. (M. volcanica), native to South America, is a traditional Peruvian medicinal plant that has multi-therapeutic properties; however, no phytochemicals have been identified from it yet. In this study, a five-step polarity-stepwise elution counter-current chromatography (CCC) was developed using methanol/water (1:5, v/v) as the stationary phase and different ratios of n-hexane, ethyl acetate, and n-butanol as mobile phases to separate the compounds from the 70% methanol extract of M. volcanica, by which six compounds with a wide range of polarities were separated in a single run of CCC and were identified as gallic acid, protocatechuic acid, 4,4'-dihydroxy-3,3'-imino-di-benzoic acid, rutin, quercitrin, and quercetin. Then, two compounds from the fractions of stepwise elution CCC were separated using conventional high-speed CCC, pH-zone-refining CCC, and preparative high-performance liquid chromatography, and identified as shikimic acid and miquelianin. These compounds are reported from M. volcanica for the first time. Notably, except for shikimic acid, all other compounds showed anti-diabetic potentials via antioxidant, antiglycation, and aldose reductase inhibition. The results suggest that the polarity-stepwise elution CCC can be used to efficiently separate or fractionate compounds with a wide range of polarities from natural products. Moreover, M. volcanica and its bioactive compounds are potent anti-diabetic agents.
Assuntos
Aldeído Redutase/antagonistas & inibidores , Antioxidantes/farmacologia , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Polygonaceae/química , Cromatografia Líquida de Alta Pressão , Distribuição ContracorrenteRESUMO
BACKGROUND: Monosialotetrahexosylganglioside (GM1) is a neuroprotective glycosphingolipid that repairs nerves. Oxaliplatin-based chemotherapy is neurotoxic. This study assessed the efficacy of GM1 for preventing oxaliplatin-induced peripheral neurotoxicity (OIPN) in colorectal cancer (CRC) patients receiving oxaliplatin-based chemotherapy. METHODS: In total, 196 patients with stage II/III CRC undergoing adjuvant chemotherapy with mFOLFOX6 were randomly assigned to intravenous GM1 or a placebo. The primary endpoint was the rate of grade 2 or worse cumulative neurotoxicity (NCI-CTCAE). The secondary endpoints were chronic cumulative neurotoxicity (EORTC QLQ-CIPN20), time to grade 2 neurotoxicity (NCI-CTCAE or the oxaliplatin-specific neuropathy scale), acute neurotoxicity (analog scale), rates of dose reduction or withdrawal due to OIPN, 3-year disease-free survival (DFS) and adverse events. RESULTS: There were no significant differences between the arms in the rate of NCI-CTCAE grade 2 or worse neurotoxicity (GM1: 33.7% vs placebo: 31.6%; P = .76) or neuropathy measured by the EORTC QLQ-CIPN20 or time to grade 2 neurotoxicity using NCI-CTCAE and the oxaliplatin-specific neuropathy scale. GM1 substantially decreased participant-reported acute neurotoxicity (sensitivity to cold items [P < .01], discomfort swallowing cold liquids [P < .01], throat discomfort [P < .01], muscle cramps [P < .01]). The rates of dose reduction or withdrawal were not significantly different between the arms (P = .08). The 3-year DFS rates were 85% and 83% in the GM1 and placebo arms, respectively (P = .19). There were no differences in toxicity between the arms. CONCLUSION: Patients receiving GM1 were less troubled by the symptoms of acute neuropathy. However, we do not support the use of GM1 to prevent cumulative neurotoxicity. (ClinicalTrials.gov number, NCT02251977).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Gangliosídeo G(M1)/administração & dosagem , Oxaliplatina/efeitos adversos , Oxaloacetatos/efeitos adversos , Doenças do Sistema Nervoso Periférico/epidemiologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Capecitabina/administração & dosagem , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina/administração & dosagem , Oxaloacetatos/administração & dosagem , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/prevenção & controle , Placebos/administração & dosagem , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Preclinical studies suggest synergistic effectiveness of ascorbic acid (AA, vitamin C) and cytotoxic agents in gastrointestinal malignancies. This phase 1 study aimed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AA combined with mFOLFOX6 or FOLFIRI regimens in patients with metastatic colorectal cancer (mCRC) or gastric cancer (mGC). METHODS: In the dose-escalation phase, patients received AA (0.2-1.5 g/kg, 3-h infusion, once daily, days 1-3) with mFOLFOX6 or FOLFIRI in a 14-day cycle until the MTD was reached. In the speed-expansion phase, AA was administered at the MTD or at 1.5 g/kg if the MTD was not reached at a fixed rate of 0.6, 0.8 or 1 g/min. Pharmacokinetics and preliminary efficacy were also assessed. RESULTS: Thirty-six patients were enrolled. The MTD was not reached. The RP2D was established as AA at 1.5 g/kg/day, days 1-3, with mFOLFOX6 or FOLFIRI. No dose-limiting toxicity (DLT) was detected during dose escalation. The most common treatment-emergent adverse events (TRAEs) were sensory neuropathy (50%), nausea (38.9%), vomiting (36.1%) and neutropenia (27.8%). Grade 3-4 TRAEs were neutropenia (13.9%), sensory neuropathy (2.8%), vomiting (2.8%), diarrhea (2.8%) and leukopenia (2.8%). AA exposure was dose-proportional. The objective response rate was 58.3%, and the disease control rate was 95.8%. No difference in efficacy was found between mCRC patients with wild-type RAS/BRAF and mutant RAS or BRAF. CONCLUSIONS: The favorable safety profile and preliminary efficacy of AA plus mFOLFOX6/FOLFIRI support further evaluation of this combination in mCRC or mGC. TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT02969681 .
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácido Ascórbico/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/efeitos adversos , Povo Asiático , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Gástricas/patologiaRESUMO
The purpose of this study was to combine morphological, microscopic, UHPLC multiple-component assay and fingerprinting studies in order to evaluate the quality of Moutan Cortex (MC) systematically. The root system of Paeonia suffruticosa was measured to compare the morphological variation and the chemical composition of different grades of MC was discussed according to previous studies. The difference between the main microscopic features of MC powder and the xylem powder is dramatic, the MC powder contains great amount of starch granules and clusters of calcium oxalate, while the xylem powder displays considerable vessels. Interestingly, the growth rings of P. suffruticosa was first reported in the xylem of the root transection, this can help to determine the growth years of the plant. Moreover, through the assay of 16 component, MC produced in Tongling and Bozhou in Anhui province were compared, content of PGG in MC produced in Bozhou was significantly higher than MC produced in Tongling (P<0.01). MC with different growth years, MC with xylem and unprocessed MC and MC decoction pieces were compared respectively by combining the results of 16 compounds assay and fingerprinting. It is proposed that the quality evaluation standard include the assay of paeoniflorin. Above all, the holistic quality difference can be evaluated more comprehensively by combining multiple analytical methods.
Assuntos
Medicamentos de Ervas Chinesas , PaeoniaRESUMO
The acute-phase proinflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) demonstrate high-level expression and pleiotropic biological effects, and contribute to the progression and persistence of rheumatoid arthritis (RA). Acid hydrarthrosis is also an important pathological characteristic of RA, and the acid-sensing ion channel 1a (ASIC1a) plays a critical role in acidosis-induced chondrocyte cytotoxicity. However, the roles of IL-1ß and TNF-α in acid-induced apoptosis of chondrocytes remain unclear. Rat adjuvant arthritis and primary articular chondrocytes were used as in vivo and in vitro model systems, respectively. ASIC1a expression in articular cartilage was increased and highly colocalized with nuclear factor (NF)-κB expression in vivo. IL-1ß and TNF-α could upregulate ASIC1a expression. These cytokines activated mitogen-activated protein kinase and NF-κB pathways in chondrocytes, while the respective inhibitors of these signaling pathways could partially reverse the ASIC1a upregulation induced by IL-1ß and TNF-α. Dual luciferase and gel-shift assays and chromatin immunoprecipitation-polymerase chain reaction demonstrated that IL-1ß and TNF-α enhanced ASIC1a promoter activity in chondrocytes by increasing NF-κB DNA-binding activities, which was in turn prevented by the NF-κB inhibitor ammonium pyrrolidinedithiocarbamate. IL-1ß and TNF-α also decreased cell viability but enhanced LDH release, intracellular Ca2+ concentration elevation, loss of mitochondrial membrane potential, cleaved PARP and cleaved caspase-3/9 expression, and apoptosis in acid-stimulated chondrocytes, which effects could be abrogated by the specific ASIC1a inhibitor psalmotoxin-1 (PcTX-1), ASIC1a-short hairpin RNA or calcium chelating agent BAPTA-AM. These results indicate that IL-1ß and TNF-α can augment acidosis-induced cytotoxicity through NF-κB-dependent up-regulation of ASIC1a channel expression in primary articular chondrocytes.
Assuntos
Acidose/patologia , Apoptose/efeitos dos fármacos , Cartilagem Articular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Interleucina-1beta/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Canais Iônicos Sensíveis a Ácido/genética , Canais Iônicos Sensíveis a Ácido/metabolismo , Acidose/genética , Acidose/metabolismo , Animais , Apoptose/genética , Artrite Experimental/genética , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Cartilagem Articular/fisiologia , Células Cultivadas , Condrócitos/fisiologia , Masculino , NF-kappa B/metabolismo , NF-kappa B/fisiologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genéticaRESUMO
An increasing number of studies reveal the significance of genetic markers in guiding target treatment and refining prognosis. This retrospective observational study aims to assess the mutation profile of metastatic colorectal cancer (mCRC) in Chinese population with the help of MassARRAY® technique platform and OncoCarta™ Panel.322 Chinese patients with mCRC who received clinical molecular testing as part of their standard care were investigated. 80 patients received cetuximab palliative treatment. 238 common hot-spot mutations of 19 cancer related genes in the OncoCarta™ Panel were tested.44 mutations in 11 genes were detected in 156 cases (48.4%). At least one mutation was identified in 38.5% (124/322) of all tested cases, two concomitant mutations in 9.0% (29/322) and three mutations in 3 cases (<1%). KRAS was the most frequently mutated gene (34.8%), followed by PIK3CA (9.6%), NRAS (4.3%), BRAF (3.4%), EGFR (2.5%) and HRAS (1.2%). Less frequent mutations were detected in PDGFRA, RET, AKT1, FGFR1, and ERBB2. Co-mutation of RAS family subtypes was observed in 5 patients, and KRAS and BRAF concurrent mutation in 1 patient. KRAS, NRAS, BRAF and PIK3CA mutations had association with some clinicopathological features statistically. Patients identified as wild-type in all 19 genes had better objective response rate when treated with cetuximab.The clinical molecular testing with OncoCarta™ Panel supplemented the limited data of mCRC in Chinese population, and offered a clearer landscape of multiple gene mutational profile in not only clinically prognostic KRAS, NRAS, BRAF and PIK3CA genes, but also less frequent mutated genes. Knowledge of these multiple gene mutation patterns may give clues in exploring interesting accompanying co-occurrence relationship or mutually exclusive relationship between mutated genes, as well as in predicting benefit of all-wild-type patients from anti-EGFR treatment.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Adenocarcinoma/patologia , Adulto , Idoso , Povo Asiático/genética , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cetuximab/uso terapêutico , Neoplasias Colorretais/patologia , Análise Mutacional de DNA , Receptores ErbB/antagonistas & inibidores , Feminino , Fluoruracila/administração & dosagem , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Estudos RetrospectivosRESUMO
BACKGROUND: Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common type of lipid storage myopathies in China. Most patients with late-onset MADD are well responsive to riboflavin. Up to now, these patients are often treated with glucocorticoids as the first-line drug because they are misdiagnosed as polymyositis without muscle biopsy or gene analysis. Although glucocorticoids seem to improve the fatty acid metabolism of late-onset MADD, the objective evaluation of their rationalization on this disorder and comparison with riboflavin treatment are unknown. METHODS: We performed a historical cohort study on the efficacy of the two drugs among 45 patients with late-onset MADD, who were divided into glucocorticoids group and riboflavin group. Detailed clinical information of baseline and 1-month follow-up were collected. RESULTS: After 1-month treatment, a dramatic improvement of muscle strength was found in riboflavin group (P < 0.05). There was no significant difference in muscle enzymes between the two groups. Significantly, the number of patients with full recovery in glucocorticoids group was less than the number in riboflavin group (P < 0.05). On the other hand, almost half of the patients in riboflavin group still presented high-level muscle enzymes and weak muscle strength after 1-month riboflavin treatment, meaning that 1-month treatment duration maybe insufficient and patients should keep on riboflavin supplement for a longer time. CONCLUSIONS: Our results provide credible evidences that the overall efficacy of riboflavin is superior to glucocorticoids, and a longer duration of riboflavin treatment is necessary for patients with late-onset MADD.
Assuntos
Glucocorticoides/uso terapêutico , Deficiência Múltipla de Acil Coenzima A Desidrogenase/tratamento farmacológico , Riboflavina/uso terapêutico , Adolescente , Adulto , Idade de Início , Criança , Estudos de Coortes , Feminino , Humanos , Erros Inatos do Metabolismo Lipídico/terapia , Masculino , Distrofias Musculares/terapia , Adulto JovemRESUMO
OBJECTIVE: To evaluate the clinical efficacy of bladder gasification and stasis dispersion combined with antibiotic therapy in the treatment of III A chronic prostatitis. METHODS: We conducted a randomized controlled clinical study on 120 III A prostatitis patients that all met the diagnostic criteria. We divided the patients into groups A, B and C of equal number to receive oral medication of sparfloxacin, sparfloxacin + tamsulosin, and sparfloxacin + herbal decoction, respectively, all for a course of 4 weeks. We evaluated the primary therapeutic indexes according to the total scores of the patients on traditional Chinese medicine (TCM) syndrome and NIH-CPSI and the secondary therapeutic indexes based on the count of white blood cells (WBC) in the expressed prostatic secretion (EPS). RESULTS: After treatment, the total scores on TCM syndrome and NIH-CPSI were significantly reduced in groups B (42.15 +/- 10.29 and 13.25 +/- 6.04) and C (41.26 +/- 11.25 and 12.38 +/- 7.19) than in A (49.43 +/- 11.09 and 17.62 +/- 5.84) ( P < 0.05), and so was the WBC count in EPS in group C (7.76 +/- 15.73) than in groups A (11.45 +/- 10.33) and B (12.28 +/- 13.81) (P < 0.05). The difference between pre- and post-treatment scores on TCM syndrome was more significant in group C (12.65 +/- 11.76) than in B (8.55 +/- 10.15) (P < 0.05). CONCLUSION: Bladder gasification and stasis dispersion combined with antibiotic therapy is effective for the treatment of III A chronic prostatitis, and therefore deserves wide clinical application.
Assuntos
Antibacterianos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Fitoterapia , Prostatite/tratamento farmacológico , Adulto , Doença Crônica , Terapia Combinada , Humanos , Masculino , Medicina Tradicional Chinesa , Prostatite/classificação , Resultado do TratamentoRESUMO
BACKGROUND: The ubiquitin editing enzyme A20 plays an important role in maintaining the homeostasis in the body Microbe-derived adjuvants are commonly used in animal models of intestinal allergy. OBJECTIVE: This study aims to investigate the role of cholera toxin-induced A20 suppression in compromising intestinal barrier function. METHODS: Human intestinal epithelial cells were cultured into monolayers as an in vitro epithelial barrier model. Ovalbumin (OVA) was used as a specific allergen to test the degrading capability of intestinal epithelial cells for the endocytic allergens. The fusion of endosomes and lysosomes in epithelial cells was observed by immunocytochemistry. The antigenicity of OVA was tested by T cell proliferation assay. RESULTS: A20 was detectable in the intestinal cell lines and mouse intestinal epithelialum. A20 was required in the degradation of endocytic allergens in HT-29 cells. The allergen, OVA, could pass through A20-deficient HT-29 monolayer barrier. Exposure to microbial adjuvant, cholera toxin, suppressed the expression of A20 in HT-29 cells, which compromised the epithelial barrier function. CONCLUSION: The microbial product, cholera toxin, interferes with the expression of A20 in intestinal epithelial cells, which compromises the intestinal epithelial barrier function.
Assuntos
Toxina da Cólera/farmacologia , Proteínas de Ligação a DNA/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Nucleares/metabolismo , Transcitose/efeitos dos fármacos , Animais , Células CACO-2 , Linhagem Celular , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Endossomos/metabolismo , Expressão Gênica/efeitos dos fármacos , Células HT29 , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Lisossomos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Ovalbumina/imunologia , Ovalbumina/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfaRESUMO
OBJECTIVE: To set up a platform for phenotype-based primary screening of drug candidates promoting neuronal subtype differentiation in embryonic stem cells (ES) with light microscope. METHODS: Hanging drop culture 4-/4+ method was employed to harvest the cells around embryoid body (EB) at differentiation endpoint. Morphological evaluation for neuron-like cells was performed with light microscope. Axons for more than three times of the length of the cell body were considered as neuron-like cells. The compound(s) that promote neuron-like cells was further evaluated. Icariin (ICA, 10(-6)mol/L) and Isobavachin (IBA, 10(-7)mol/L) were selected to screen the differentiation-promoting activity on ES cells. Immunofluorescence staining with specific antibodies (ChAT, GABA) was used to evaluate the neuron subtypes. RESULTS: The cells treated with IBA showed neuron-like phenotype, but the cells treated with ICA did not exhibit the morphological changes. ES cells treated with IBA was further confirmed to be cholinergic and GABAergic neurons. CONCLUSION: Phenotypic screening with light microscope for molecules promoting neuronal differentiation is an effective method with advantages of less labor and material consuming and time saving, and false-positive results derived from immunofluorescence can be avoided. The method confirms that IBA is able to facilitate ES cells differentiating into neuronal cells, including cholinergic neurons and GABAergic neurons.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Células-Tronco Embrionárias/citologia , Neurônios/citologia , Animais , Diferenciação Celular/fisiologia , Linhagem Celular , Corpos Embrioides/citologia , Camundongos , Regeneração Nervosa/efeitos dos fármacos , FenótipoRESUMO
BACKGROUND: Moxifloxacin-containing triple therapy has been suggested as an alternative second-line therapy for Helicobacter pylori infection. AIMS: To systematically review the efficacy and tolerance of moxifloxacin-containing triple therapy in second-line H. pylori eradication, and to conduct a meta-analysis of studies comparing this regimen with bismuth-containing quadruple therapy. MATERIALS AND METHODS: Electronic databases including Medline, Embase, Cochrane controlled trials register, Web of Science, PubMed, Chinese Biomedical Literature Database (updated to December 2010), and manual searches were conducted. A meta-analysis of all randomized controlled trials (RCTs) comparing moxifloxacin-containing triple therapy to bismuth-containing quadruple therapy in the second-line treatment of H. pylori infection was performed. RESULTS: Seven RCTs including 787 patients were assessed. The meta-analysis showed that the eradication rate in the moxifloxacin group was significantly higher than that in the quadruple therapy group (74.9 vs 61.4%, OR 1.89, 95% CI: 1.38-2.58, p < .0001); besides, the rates of side effects and discontinuing therapy because of side effects in the moxifloxacin group were significantly lower than those in the quadruple therapy group (side effects: 10.1 vs 27.8%, OR 0.27, 95% CI: 0.18-0.41, p < .00001; discontinuing therapy because of side effects: 1.4 vs 8.2%, OR 0.18, 95% CI: 0.08-0.40, p < .0001). These results were constant in the sensitivity analyses. CONCLUSION: Moxifloxacin-containing triple regimen is more effective and better tolerated than the bismuth-containing quadruple therapy in the second-line treatment of H. pylori infection.
Assuntos
Compostos Aza/uso terapêutico , Bismuto/uso terapêutico , Quimioterapia Combinada/métodos , Infecções por Helicobacter/tratamento farmacológico , Quinolinas/uso terapêutico , Fluoroquinolonas , Humanos , Moxifloxacina , Resultado do TratamentoRESUMO
OBJECTIVE: To observe the sedative and analgesic effects of transcutaneous electrical acupoint stimulation (TEAS) in patients with artificial abortion operation. METHODS: Ninety patients, with American Society of Anesthesiologists (ASA) physical status I - II, and scheduled for artificial abortion operation, were randomly divided into three groups, 30 cases in each group. The patients in group A were treated with TEAS on Neiguan (PC 6) and Taichong (LR 3), in group B with paracervical block anesthesia (BA), and in group c with both TEAS and BA. Continuous monitoring of the mean arterial blood pressure (MAP), heart rate (HR), oxygen saturation and bispectral index (BIS) of the patients lasted to 30 min after the operation. The BIS, Visual Analogue Scale (VAS) during the operation and the adverse reactions after the operation were analyzed. RESULTS: After 15 minutes TEAS, the BIS in group A and C were decreased significantly, with no significant difference between the two groups (P > 0.05) and being both better than that in group B (both P < 0.05), which had no significant change. There were no significant differences in the VAS among the three groups (all P > 0.05), while the adverse reactions in both group A and C were lower than that in group B (both P < 0.05). CONCLUSION: TEAS has sedative and analgesic effect during artificial abortion operation and can decrease the adverse reactions.
Assuntos
Aborto Induzido/efeitos adversos , Analgesia por Acupuntura , Pontos de Acupuntura , Manejo da Dor , Adulto , Eletroacupuntura , Feminino , Frequência Cardíaca , Humanos , Oxigênio/metabolismo , Dor/metabolismo , Dor/fisiopatologia , Medição da Dor , Adulto JovemRESUMO
OBJECTIVE: To assess the effect of Shenmai Injection (SMI) on left ventricular diastolic function (LVDF) in patients with chronic heart failure (CHF) by tissue Doppler imaging (TDI). METHODS: Sixty-four CHF patients were randomly assigned to two groups, the observation group and the control group. Basic treatment including polarized liquid therapy was given to all the patients. In addition, SMI was given to patients of the observation group. The treatment duration was 14 days. TDI was performed in all the patients 3 days prior to the initiation of the treatment and one week after the medication to measure the average movement velocity of the mitral ring of the left ventricle at the early systolic stage and late diastolic stage (Ea and Aa); the outcomes were compared with the corresponding parameters obtained from blood flow Doppler echocardiography, namely, the velocity of the E-wave (E) and A-wave (A). RESULTS: After treatment, Ea and Ea/Aa increased and Aa decreased significantly in the observation group (P<0.05). In the control group, although some improvement was seen, there was no statistically significant change (P>0.05). No statistical significance was shown between groups in these parameters after treatment. CONCLUSION: TDI assessment shows that SMI could effectively improve the LVDF in CHF patients.
Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Insuficiência Cardíaca Diastólica/diagnóstico por imagem , Insuficiência Cardíaca Diastólica/tratamento farmacológico , Função Ventricular/efeitos dos fármacos , Adulto , Idoso , Fármacos Cardiovasculares/administração & dosagem , Fármacos Cardiovasculares/efeitos adversos , Fármacos Cardiovasculares/farmacologia , Doença Crônica , Diástole/efeitos dos fármacos , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/efeitos adversos , Ecocardiografia Doppler , Feminino , Insuficiência Cardíaca Diastólica/fisiopatologia , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Disfunção Ventricular Esquerda/tratamento farmacológicoRESUMO
BACKGROUND AND OBJECTIVE: Irinotecan (CPT-11), oxaliplatin, 5-fluorouracil (5-FU) and capecitabine are main active agents for advanced colorectal cancer. FORFIRI regimen is recommended for the patients who were treated with oxaliplatin plus 5-FU or capecitabine previously. This study was to investigate the efficacy and safety of FORFIRI regimen in treating advanced colorectal cancer failing to prior oxaliplatin-based chemotherapy, and analyze the impacts of clinical factors on the responses. METHODS: A total of 90 patients with advanced colorectal adenocarcinoma, who had received prior adjuvant FOLFOX6 regimen and progressed within 12 months after the completion of therapy or had no response to prior FOLFOX6/CapeOX regimen as first-line therapy, were treated with FORFIRI regimen. The efficacy and adverse events were observed. RESULTS: Of the 81 evaluable patients, two achieved complete remission, 20 achieved partial remission and 34 had stable disease. The overall response rate was 27.2% and disease control rate was 69.1%. The median time to progression was 6.8 months (95% CI, 4.9-8.8 months) and median overall survival time was 18.8 months (95% CI, 17.5-20.2 months). The main adverse events time were nausea, vomiting, neutropenia, alopecia, fatigue, impaired liver function, oral mucositis and diarrhea. Grade III adverse events included alopecia in 15 patients (16.7%), vomiting in 10 patients (11.1%), nausea in eight patients (8.9%), neutropenia in five patients (5.6%), impaired liver function in two patients (2.2%) and oral mucositis in two patients (2.2%). CONCLUSION: FOLFIRI regimen is effective and well-tolerated as salvage therapy for advanced colorectal cancer failing to prior FOLFOX6/CapeOX regimen, and thus can be used widely.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias do Colo/patologia , Progressão da Doença , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Irinotecano , Leucovorina/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Neoplasias Retais/patologia , Indução de Remissão , Terapia de Salvação , Taxa de Sobrevida , Vômito/induzido quimicamente , Adulto JovemRESUMO
OBJECTIVE: To compare therapeutic effects of acupuncture and Chinese drug on oligospermia and asthenospermia in the male infertility. METHODS: Two hundred and thirty-one cases were divided into 3 groups. The electroacupuncture group (n = 71) were treated with acupuncture at Qihai (CV 6), Guanyuan (CV 4), Zhongji (CV 3), etc., the Chinese drug group (n = 82) with oral administration of Chinese drug Wuzi Yanzong Pill and the acupuncture plus medication group (n = 78) with both electroacupuncture and oral administration of the Chinese drug. Changes of semen routine examination and the acrosome enzyme activity were observed before and after treatment in the 3 groups. RESULTS: The effective rate was 67.6% in the electroacupuncture group, 68.3% in the Chinese drug group and 84.6% in the acupuncture plus medication group, the acupuncture plus medication group being significantly better than both the electroacupuncture and the Chinese drug group (P < 0.05); after treatment, the semen density, vitality and the acrosome enzyme activity were increased in the 3 groups, with more obvious increase in the acupuncture plus medication group. CONCLUSION: Both electroacupuncture and Chinese drug Wuzi Yanzong Pill can improve the semen quality, increase the pregnancy rate in the patient of male interfile with oligospermia and asthenospermia, and the effect of the combined treatment of acupuncture and Chinese drug is the best.
Assuntos
Terapia por Acupuntura , Medicamentos de Ervas Chinesas/uso terapêutico , Infertilidade Masculina/terapia , Adulto , Terapia Combinada , Eletroacupuntura , Humanos , Infertilidade Masculina/tratamento farmacológico , Infertilidade Masculina/fisiopatologia , Masculino , Contagem de Espermatozoides , Motilidade dos EspermatozoidesRESUMO
The groundwater petroleum contaminant remediation effect by air sparging was investigated in an oil field. The results show that the soil geological situation has great influence on the air distribution, and the shape of air distribution is not symmetrical to the air sparging (AS) well as axis. The influence distance in the left of AS well is 6 m, and only 4 m in the right. The petroleum removal rate can reach 70% in the zone with higher air saturation, but only 40% in the zone with lower air saturation, and the average petroleum removal rate reaches 60% in the influence zone for 40 days continuous air sparging. The petroleum components in groundwater were analyzed by GC/MS (gas chromatogram-mass spectrograph) before and after experiments, respectively. The results show that the petroleum removal rate has relationship with the components and their properties. The petroleum components with higher volatility are easily removed by volatilization, but those with lower volatility are difficult to remove, so a tailing effect of lingering residual contaminant exists when the air sparging technology is adopted to treat groundwater contaminated by petroleum products.
Assuntos
Petróleo , Movimentos da Água , Poluentes Químicos da Água/análise , Poluição Química da Água/prevenção & controle , Ar , Volatilização , Poluentes Químicos da Água/química , Poluição Química da Água/análiseRESUMO
OBJECTIVE: To investigate the protective effects of icaritin (ICT) on apoptosis of primarily cultured rat neurons induced by Abeta(25-35) peptide and its mechanism. METHODS: Cortical neurons from rat embryonic cortical on d17 pregnancy were cultured in neural basal medium for 7 days. Icaritin (ICT) was pre-incubated for 24 h before adding Abeta(25-35) peptide and then the cells were incubated for 72 h. Neuroprotective effects of ICT were evaluated by MTT assay, LDH level in medium and cell morphological observation. Meanwhile, apoptosis was determined by JC-1 staining for mitochondria membrane potential (DeltaPsim) and AO/EB double staining for genetic damage of nucleoli in monolayer cells. RESULTS: 0.1 micromol.L(-1) ICT pre-incubation for 24 h prevented rat neurons from Abeta(25-35) peptide induced apoptosis significantly as demonstrated by MTT, LDH assay and morphological observation. AO/EB double staining also indicated that ICT prevented neurons from apoptosis. JC-1 staining further showed that ICT prevented decreasing of mitochondrial DeltaPsim induced by Abeta(25-35) peptide. CONCLUSION: ICT could protect primarily cultured rat neurons from Abeta(25-35) peptide induced apoptosis.
Assuntos
Peptídeos beta-Amiloides/toxicidade , Apoptose/efeitos dos fármacos , Flavonoides/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/embriologia , Medicamentos de Ervas Chinesas/farmacologia , Neurônios/citologia , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To observe therapeutic effect of electrical plum-blossom needle for treatment of juvenile myopia and biological effect on ocular tissue and structures. METHODS: One hundred and sixty cases with mild myopia (diopter < 3.00D) were randomly divided into two groups, a treatment group and a control group. The treatment group were treated with electrical plum-blossom needle therapy, tapping Jingming (BL 1), Chengqi (ST 1), Taiyang (EX-HN 5) and Neiguan (PC 6), and the control group with Tropicamide eye drops. The changes of vision, diopter, corneal refractive power, ocular-axial length, lens and ciliaris thickness were observed before and after treatment. RESULTS: The total effective rate was 80.0% in the treatment group and 58.1% in the control group, with a very significant difference between the two groups (P < 0.01); the two therapies could decrease the thickness of lens and ciliaris, and eliminate spasm of ciliary muscle, however the electrical plum-blossom needle therapy had more obvious action (P < 0.05); the two therapies had no effect on the corneal refractive power and ocular-axial length. CONCLUSION: The electrical plum-blossom needle therapy is an effective method for increasing vision, correcting ametropia and delaying development of myopia.