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Front Cell Infect Microbiol ; 11: 627917, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968796


Candida albicans (C. albicans) is an opportunistic human fungal pathogen that can cause severe infection in clinic. Its incidence and mortality rate has been increasing rapidly. Amphotericin B (AMB), the clinical golden standard antifungal agent, has severe side effects that limit its clinical application. Thus, lowering the concentration and increasing the efficacy of AMB in a combinatorial antifungal therapy have been pursued by both industry and academia. Here we identify that fingolimod (FTY720), an immunomodulatory drug used for oral treatment of relapsing-remitting multiple sclerosis, can potentiate the efficacy of AMB against C. albicans growth synergistically. Furthermore, we observe an antifungal efficacy of FTY720 in combination with AMB against diverse fungal pathogens. Intriguingly, cells treated with both drugs are hypersensitive to endothelial endocytosis and macrophage killing. This is later found to be due to the hyperaccumulation of reactive oxygen species and the corresponding increase in activities of superoxide dismutase and catalase in the cells that received combinatorial treatment. Therefore, the combination of AMB and FTY720 provides a promising antifungal strategy.

Anfotericina B , Antifúngicos , Candida albicans , Cloridrato de Fingolimode , Humanos , Testes de Sensibilidade Microbiana
Clin Chem Lab Med ; 56(4): 614-624, 2018 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-29166262


BACKGROUND: The aim of the study was to determine the prevalence and clinical associations of antiphosphatidylserine/prothrombin antibodies (aPS/PT) with thrombosis and pregnancy loss in Chinese patients with antiphospholipid syndrome (APS) and seronegative APS (SNAPS). METHODS: One hundred and eighty six Chinese patients with APS (67 primary, 119 secondary), 48 with SNAPS, 176 disease controls (79 systemic lupus erythematosus [SLE], 29 Sjogren's syndrome [SS], 30 ankylosing spondylitis [AS], 38 rheumatoid arthritis [RA]) and 90 healthy donors were examined. IgG and IgM aPS/PT, IgG/IgM/IgA anticardiolipin (aCL) and IgG/IgM/IgA anti-ß2-glycoprotein I (anti-ß2GPI) antibodies were tested by ELISA. RESULTS: One hundred and sixty (86.0%) of APS patients were positive for at least one aPS/PT isotype. One hundred and thirty five (72.6%) were positive for IgG aPS/PT, 124/186 (66.7%) positive for IgM aPS/PT and 99 (53.2%) positive for both. Approximately half of the SNAPS patients were positive for IgG and/or IgM aPS/PT. Highly significant associations between IgG aPS/PT and venous thrombotic events (odds ratio [OR]=6.72) and IgG/IgM aPS/PT and pregnancy loss (OR=9.44) were found. Levels of IgM aPS/PT were significantly different in APS patients with thrombotic manifestations and those with fetal loss (p=0.014). The association between IgG/IgM aPS/PT and lupus anticoagulant (LAC) was highly significant (p<0.001). When both were positive, the OR for APS was 101.6. Notably, 91.95% (80/87) of LAC-positive specimens were positive for IgG and/or IgM aPS/PT, suggesting aPS/PT is an effective option when LAC testing is not available. CONCLUSIONS: Anti-PS/PT antibody assays demonstrated high diagnostic performance for Chinese patients with APS, detected some APS patients negative for criteria markers and may serve as potential risk predictors for venous thrombosis and obstetric complications.

Anticorpos Antifosfolipídeos/análise , Síndrome Antifosfolipídica/diagnóstico , Complicações do Trabalho de Parto/diagnóstico , Trombose Venosa/diagnóstico , Adulto , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/epidemiologia , Síndrome Antifosfolipídica/imunologia , Biomarcadores/análise , China/epidemiologia , Feminino , Humanos , Masculino , Complicações do Trabalho de Parto/epidemiologia , Complicações do Trabalho de Parto/imunologia , Fosfatidilserinas/imunologia , Valor Preditivo dos Testes , Gravidez , Protrombina/imunologia , Fatores de Risco , Trombose Venosa/epidemiologia , Trombose Venosa/imunologia
Chin Med J (Engl) ; 123(13): 1639-44, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20819621


BACKGROUND: Hemoconcentration may be an important factor that determines the progression of severe acute pancreatitis (SAP). In addition, it has been proposed that biomarkers may be useful in predicting subsequent necrosis in SAP. However, it is still uncertain whether hemodilution in a short term can improve outcome. We aimed to investigate the effect of rapid hemodilution on the outcome of patients with SAP. METHODS: One hundred and fifteen patients were admitted prospectively according to the criteria within 24 hours of SAP onset. Patients were randomly assigned to either rapid hemodilution (hematocrit (HCT) < 35%, n = 56) or slow hemodilution (HCT > or = 35%, n = 59) within 48 hours of onset. Balthazar CT scores were calculated on admission, day 7, and day 14, after onset of the disease. Time interval for sepsis presented, incidence of sepsis within 28 days and in-hospital survival rate were determined. RESULTS: The amount of fluid used in rapid hemodilution was significantly more than that used in slow hemodilution (P < 0.05) on the admission day, the first day, and the second day. There were significant differences between the rapid and slow hemodilution group in terms of hematocrit, oxygenation index, pH values, APACHE II scores and organ dysfunction at different time during the first week. There were significant differences in the time interval to sepsis in rapid hemodilution ((7.4 +/- 1.9) days) compared with the slow hemodilution group ((10.2 +/- 2.3) days), and the incidence of sepsis (78.6%) was higher in the rapid group compared to the slow (57.6%) in the first 28 days. The survival rate of the slow hemodilution group (84.7%) was better than the rapid hemodilution (66.1%. P < 0.05). CONCLUSIONS: Rapid hemodilution can increase the incidence of sepsis within 28 days and in-hospital mortality. Hematocrit should be maintained between 30%-40% in the acute response stage.

Doença Aguda/mortalidade , Doença Aguda/terapia , Hemodiluição/efeitos adversos , Pancreatite/mortalidade , Pancreatite/terapia , Sepse/etiologia , Sepse/mortalidade , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
Zhonghua Wai Ke Za Zhi ; 48(7): 496-501, 2010 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-20646657


OBJECTIVE: To investigate the spectrum of bacteria and fungi in different sites in severe acute pancreatitis (SAP). METHODS: The prospective study was performed in 205 patients with SAP treated from January 2000 to December 2008. The Infection rate of bacteria and fungi was observed prospectively in pancreatic necrosis and(or) pus form abdomen, body fluids and deep vein catheter in SAP. Body fluids and pancreatic necrosis were cultured twice a week. Central venous catheter was cultured when it had been placed for two weeks. Blood was cultured for bacteria and fungi when body temperature was more than 39 degrees C. Constituent ratio of bacteria and fungi was observed in different sites and in all sites within 28 days after onset of SAP. RESULTS: There were 937 pathogens, among which infection rates of gram-negative bacteria was higher than gram-positive bacteria and fungi (P < 0.05), the infection rates of gam-positive bacteria and fungi were similar. Infection rates of gram-negative bacteria in pancreatic necrosis (55.2%), bile (55.4%), blood (68.1%) and central venous catheter (44.4%) were increased significantly (P < 0.05) compared with gram-positive bacteria and (30.2%, 33.9%, 23.4%, 38.9%) and fungi (14.6%, 10.7%, 8.5%, 16.7%); however, infection rate of fungi (59.6%) was increased significantly (P < 0.05) compared with gram-negative bacteria (24.0%) and gram-positive bacteria (16.3%) in urine; infection rate of gram-negative bacteria (53.2%) was significantly higher (P < 0.05) than that of fungi (27.1%) and gram-positive bacteria (19.7%) in sputum. Infection rate of non-zymogenic bacteria (Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia) in gram-negative bacteria in pancreatic necrosis, bile, blood, central venous catheter and sputum was significantly higher than that of zymogenic bacteria (Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae) (P < 0.01); infection rate of zymogenic bacteria (Klebsiella pneumoniae, Escherichia coli) was higher significantly (P < 0.01) than that of non-zymogenic bacteria (Pseudomonas aeruginosa, Acinetobacter baumannii). Infection rate of staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus haemolyticus was significantly higher (P < 0.05) than that of Enterococcus faecalis and Enterococcus faecium in pancreatic necrosis and sputum;but infection rate of Enterococcus faecium in bile and urine was significantly higher than other gram-positive bacteria (P < 0.05). There was not difference among gram-positive bacteria;however, infection rate of Staphylococcus epidermidis in central venous catheter was increased significantly (P < 0.05). Infection rate of candida mycoderma in pancreatic necrosis, bile, urine and sputum was significantly higher than that of tricho bacteria (P < 0.05). The peak of infection rate of microbes in body fluid was within 2 to 3 weeks. CONCLUSIONS: Constituent ratio in gram-negative, gram-positive bacteria and fungi as well as their species in different sites is diverse. The peak of infection rate of microbes is 2 to 3 weeks after onset of the disease.

Bactérias/isolamento & purificação , Fungos/isolamento & purificação , Pancreatite/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
World J Gastroenterol ; 15(44): 5604-9, 2009 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-19938202


AIM: To investigate the role of sex hormones in the early postoperative complications of gastrointestinal diseases. METHODS: A total of 65 patients who underwent operations for gastric and colorectal diseases (mainly malignant diseases) were included in the study. Peripheral venous blood samples were collected at different times for analysis of estradiol, testosterone and progesterone. The only study endpoint was analysis of postoperative complications. RESULTS: Patients of both sexes were uniform but postoperative complication rate was significantly higher in female patients (P = 0.027). There was no significant association of estradiol and progesterone with postoperative complications. Testosterone levels in complicated patients were significantly lower than in uncomplicated patients (P < 0.05). Area under the receiver operating characteristic curve showed that a lower value of testosterone was a predictor for higher complication rate (P < 0.05), and a lower value of testosterone at later times after surgery was a better predictor of complications. CONCLUSION: Patients with low testosterone level were prone to higher postoperative complications, which was evident in both sexes. However, further studies are necessary to support this result.

Gastroenteropatias/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Testosterona/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/cirurgia , Estradiol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Progesterona/sangue , Fatores de Risco , Fatores Sexuais , Neoplasias Gástricas/cirurgia , Testosterona/sangue
Clin Vaccine Immunol ; 16(11): 1700-3, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19776197


A city-wide cytomegalovirus serosurvey was conducted in Shanghai, China, and associated parameters were calculated by employing the catalytic model. The lowest seroprevalence was 60.37%, found in the >1- to 3-year age group. The value increased rapidly with age until 25 years, when a value of 97.03% was found, caused by the high force of infection (12.69) and by the reproductive rate (8.89).

Infecções por Citomegalovirus/epidemiologia , Citomegalovirus/imunologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Número Básico de Reprodução , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Gravidez , Estudos Soroepidemiológicos , Adulto Jovem