Application of StrucGP in medical immunology: site-specific N-glycoproteomic analysis of macrophages / 医学前沿

The structure of N-glycans on specific proteins can regulate innate and adaptive immunity via sensing environmental signals. Meanwhile, the structural diversity of N-glycans poses analytical challenges that limit the exploration of specific glycosylation functions. In this work, we used THP-1-derived macrophages as examples to show the vast potential of a N-glycan structural interpretation tool StrucGP in N-glycoproteomic analysis. The intact glycopeptides of macrophages were enriched and analyzed using mass spectrometry (MS)-based glycoproteomic approaches, followed by the large-scale mapping of site-specific glycan structures via StrucGP. Results revealed that bisected GlcNAc, core fucosylated, and sialylated glycans (e.g., HexNAc4Hex5Fuc1Neu5Ac1, N4H5F1S1) were increased in M1 and M2 macrophages, especially in the latter. The findings indicated that these structures may be closely related to macrophage polarization. In addition, a high level of glycosylated PD-L1 was observed in M1 macrophages, and the LacNAc moiety was detected at Asn-192 and Asn-200 of PD-L1, and Asn-200 contained Lewis epitopes. The precision structural interpretation of site-specific glycans and subsequent intervention of target glycoproteins and related glycosyltransferases are of great value for the development of new diagnostic and therapeutic approaches for different diseases.

Glicopeptídeos: aspectos farmacológicos e aplicações clínicas / Glycopeptides: pharmacological aspects and clinical applications / Glicopeptidos: aspectos farmacológicos y aplicaciones clínicas

O uso indiscriminado dos antimicrobianos tem gerado um problema significativo na saúde pública, acarretando impactos negativos como fracasso na farmacoterapia frente as infecções bacterianas e aumentos nos custos assistenciais. Esta revisão narrativa tem como objetivo descrever as propriedades farmacocinéticas e farmacodinâmicas e aplicações clínicas dos principais antibióticos pertencentes a classe dos glicopeptídeos. A busca de artigos foi realizada nas seguintes bases de dados: Literatura Latino Americana e do Caribe em Ciências da Saúde (LILACS/PUBMED), SciELO (Scientific Electronic Library Online) e Biblioteca Virtual em Saúde (BVS). A vancomicina e a teicoplanina são fármacos de primeira linha no tratamento de infecções por bactérias gram-positivas com resistência a outros antibióticos. Ambos apresentam estruturas cíclicas complexas, contendo aminoácidos ligados a grupos de carboidratos que lhe conferem propriedades únicas. A administração dos glicopetídeos deve ponderar fatores relacionados ao paciente como faixa etária, função renal, desnutrição e obesidade devido a sua heterogeneidade farmacocinética, por isso o monitoramento sérico é recomendado para assegurar concentrações plasmáticas efetivas. Diante do exposto, o uso adequado e baseado em evidência científica dessa importante classe de antibióticos visa otimizar o tratamento farmacoterapêutico e diminuir o avanço da resistência bacteriana.

The indiscriminate use of antimicrobials has generated a significant problem in public health, causing negative impacts such as failure in pharmacotherapy against bacterial infections and increases in healthcare costs. This narrative review aims to describe the pharmacokinetic and pharmacodynamic properties and clinical applications of the main antibiotics belonging to the class of glycopeptides. The search for articles was carried out in the following databases: Latin American and Caribbean Literature in Health Sciences (LILACS/PUBMED), SciELO (Scientific Electronic Library Online), and Virtual Health Library (BVS). Vancomycin and teicoplanin are first- line drugs in infections caused by gram-positive bacteria it resistant to other antibiotics. Both have complex cyclic structures containing amino acids linked to carbohydrate groups that give them unique properties. The administration of glycopeptides must consider patient-related factors such as age group, renal function, malnutrition, and obesity due to its pharmacokinetic heterogeneity. Therefore, serum monitoring is recommended to ensure effective plasma concentrations. Thus, the proper use based on scientific evidence of this important class of antibiotics aims to optimize pharmacotherapeutic treatment and reduce the progress of bacterial resistance.

El uso indiscriminado de antimicrobianos ha generado un problema impor- tante en la salud pública, provocando impactos negativos como el fracaso en la farmaco- terapia contra las infecciones bacterianas y el aumento de los costos sanitarios. Esta revi- sión narrativa tiene como objetivo describir las propiedades farmacocinéticas, farmaco- dinámicas y aplicaciones clínicas de los principales antibióticos pertenecientes a la clase de los glicopéptidos. La búsqueda de artículos se realizó en las siguientes bases de datos: Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS/PUBMED), SciELO (Scientific Electronic Library Online) y Biblioteca Virtual en Salud (BVS). La vancomicina y la teicoplanina son fármacos de primera línea en el tratamiento de infec- ciones causadas por bacterias grampositivas resistentes a otros antibióticos. Ambos tienen estructuras cíclicas complejas, que contienen aminoácidos unidos a grupos de carbohi- dratos que les otorgan propiedades únicas. La administración de glicopéptidos debe con- siderar factores relacionados con el paciente, como el grupo de edad, la función renal, la desnutrición y la obesidad debido a su heterogeneidad farmacocinética, por lo que se re- comienda el monitoreo sérico para asegurar concentraciones plasmáticas efectivas. En vista de lo anterior, el uso adecuado basado en la evidencia científica de esta importante clase de antibióticos tiene como objetivo optimizar el tratamiento farmacoterapéutico y reducir la propagación de resistencias bacterianas.

Label-free quantitative peptidomics-based analysis on glycopeptides in deerhorn gelatin and deer-hide gelatin / 中国中药杂志

Nano-LC-MS/MS was used to analyze trypsin digested deer-horn gelatin( DCG) and deer-hide gelatin( DHG) samples.The glycopeptides in DCG and DHG were quantified by Label-free quantitative( LFQ) peptidomics,on the basis of which the glycopeptides with significant difference in DCG and DHG were determined. As a result,5 736 peptides were identified from DCG samples,including 213 galactosyl-hydroxylysine containing peptides( Gal-Hyl-peptides) and 102 glucosyl-galactosyl-hydroxylysine containing peptides( Glc-Gal-Hyl-peptides),while 6 836 peptides were identified from DHG samples,among which there were 250 Gal-Hyl-peptides and 98 Glc-Gal-Hyl-peptides. With over 3-fold peak area difference and highly significant intergroup difference( P < 0. 01) as the screening criteria,444 differential peptides were determined in DCG and DHG,including 16 Gal-Hyl-peptides and 5 Glc-Gal-Hyl-peptides. Then XIC peak shapes,standard deviation of peak area,and fold change were applied for further screening and 5 glycopeptides with significant differences in DCG and DHG were confirmed,which could serve as potential biomarkers for distinguishing DCG and DHG. The present study provided ideas and strategies for the in-depth investigation on the discrimination of DCG and DHG and is of good theoretical significance and application value for the further research on chemical constituents and quality control of gelatin derived Chinese medicinals.

Presencia de Enterocccus VanB a nivel intestinal en pacientes de la Unidad de hemodiálisis y cuidados intensivos del Hospital "Luís Ortega", en Porlamar, Estado Nueva Esparta

Introducción: Pacientes hospitalizados, portadores de enterococos resistentes a los glicopéptidos, son una bomba de tiempo, ya que largas estadías y terapias antibióticas prolongadas, permiten la translocación de esas cepas y la aparición de endocarditis o infecciones del tracto urinario. Metodología: En un estudio realizado en las Unidades de hemodiálisis y Terapia Intensiva en el Hospital "Luís Ortega" de Porlamar en el primer semestre del año 2008, se muestrearon 54 pacientes. Resultados: El estudio molecular mostró la presencia de la especie E. faecalis (475 pb), sensible a linezolid, gentamicina, estreptomicina y teicoplanina. El genotipo de resistencia encontrado en las cepas fue vanB (647 pb). La prevalencia de cepas VanB fue de 4 % en el servicio de HD. Ninguno de los pacientes de Terapia Intensiva estaba colonizado por cepas con alto nivel de resistencia a glicopéptidos. Conclusiones: Los estudios de vigilancia epidemiológica son fundamentales para la detección de bacterias multirresistentes en pacientes hospitalizados y evitar su diseminación en los servicios.

Introduction: Hospitalized patients with resistant to glycopeptides enterococci, are a time bomb, since long stays and prolonged antibiotic therapies allow the translocation of these strains and the occurrence of endocarditis or infections of the urinary tract. Methodology: In a study carried out on Hemodialysis and Intensive care wards on "Luís Ortega" Hospital, from Porlamar, during the first semester of 2008, 54 patients were sampled. Results: Molecular study shown E. faecalis specie (475 pb), susceptible to linezolid, gentamycin, streptomycin, and teicoplanin. Resistance genotype found was vanB (647 pb). Prevalence of VanB strains on HD ward was 4 %. No one patient of Intensive Care Unit had high level glycopeptides-resistant strains. Conclusions: Epidemiological surveillance studies are essential for the detection of multiresistant bacteria in hospitalized patients and avoid their dissemination in services.

Determinación de cepas de Enterococcus resistentes a antibióticos glicopéptidos en pacientes hospitalizados en el Hospital "Santos Aníbal Dominicci", Carúpano, Estado Sucre

Introducción: El impacto clínico de infecciones causadas por cepas de enterococos resistentes a glicopéptidos, es encontrar la terapia adecuada para salvar la vida de ese paciente, además de la transferencia horizontal de determinantes de resistencia. Es un reto determinar el origen de la cepa productora del cuadro infeccioso (endógeno o exógeno). Metodología: Se estudiaron 111 hisopados rectales y muestras de heces de pacientes en hemodiálisis y Unidad de Cuidados Intensivos del Hospital "Santos Aníbal Dominicci" (HSAD) de Carúpano, Venezuela, durante el período de febrero­julio 2007, con el objeto de determinar pacientes portadores de cepas de Enterococcus resistentes a los glicopéptidos. El aislamiento de Enterococcus se realizó en agar bilis esculina azida con y sin vancomicina (6 mg/ mL); a las cepas crecidas en cribado se les determinó la concentración mínima inhibitoria (CMI). La detección de la ligasa de resistencia se hizo por PCR múltiple. Resultados: La CMI de vancomicina estaba entre 8 y 16 mg/L, para 5 y 19 cepas respectivamente. Las cepas son intrínsecamente resistentes, tienen el genotipo vanC en 24 aislamientos: 15 vanC1 (815-bp) y 9 vanC2 (827- bp). Conclusiones: Es necesario mantener un sistema de vigilancia mediante cultivos para identificar pacientes colonizados con cepas con alto nivel de resistencia a vancomicina.

Introduction: The clinical impact of infections caused by strains of enterococci resistant to glycopeptides is to find the appropriate therapy to save the life of the patient, in addition to the horizontal transfer of resistance determinants. It is a challenge to determine the origin of the infectious (endogenous or exogenous) disease producing strain. Methodology: One hundred and ten rectal swabs and stool samples from patients in the hemodialysis unit and Intensive Care Unit of hospital "Santos Anibal Dominicci" (HSAD) in Carupano, Sucre state, Venezuela, were studied during February-July 2007 in order to determine which patients carried glycopeptideresistant Enterococcus strains. Isolation of Enterococcus was made via Bile Esculin Azide Agar with and without vancomycin (6 µg/mL). To the strains grown in screening were determined the Minimum Inhibitory Concentration (MIC). Detection of resistant ligases was done by multiplex PCR. Results: Minimun Inhibitory Concentration (MIC) levels were 8 mg/L and 16 mg/L for 5, and 19 strains, respectively. The strains are inherently resistant, have the vanC genotype in 24 isolates: 15 vanC1 (815-bp), and 9 vanC2 (827-bp). Conclusions: It could be helpful to create a surveillance system with a vancomycin screening to detect colonized patients with high level of glycopeptides resistant strains.

Clinical application of glycopeptide antibiotics in hospitalized patients / 中国感染控制杂志

Objective To survey the clinical application of glycopeptide antibiotics in hospitalized patients, and evaluate the rationality of drug use, so as to provide reference for rational clinical drug use.Methods A retrospective study was conducted to investigate the application of glycopeptide antibiotics among inpatients in a hospital from January to December in 2014, relevant clinical data were recorded.Results A total of 727 cases were included , 471 (64.79%) of which were infected cases.Respiratory tract infection was the main site of both healthcare-associated infection and community-associated infection (39.17% and 45.98%, respectively).The average days of glycopeptide antibiotic use were 6.06 day (4 403/727).Patients who used glycopeptide antibiotics were mainly from intensive care unit, department of oncology, and department of neurosurgery, accounting for 20.36%(n=148) , 12.10%(n=88), and 11.14%(n=81) respectively.Glycopeptide was used in 338 patients(46.49%),the average types of combined use was 4.43, triple and above was used in 99 patients(13.62%),combination of the second generation cephalosporins was the highest(20.48%).450(61.90%) patients used vancomycin, 260(35.76%)used teicoplanin,17(2.34%)used both vancomycin and teicoplanin.A total of 847 pathogenic strains were isolated, the major were Acinetobacter baumannii (n=111, 13.10%), Klebsiella pneumoniae (n=80, 9.45%), Pseudomonas aeruginosa (n=68, 8.03%), and Staphylococcus aureus (n=54 , 6.37%), methicillin-resistant Staphylococcus aureus was 50 strains.490 (67.40%) patients treated with glycopeptide antibiotics were effective.Of 727 patients, 86 (11.83%) used antibiotics rationally, 315(43.33%) basically rational,and 326 (44.84%) irrationally.Conclusion Application of glycopeptide antibiotics in this hospital is basically rational, but indications should be paid attention.

Clinical Observation of Recombinant Human Interferon α2b Combined with Bozhi Glycopeptides and Thymopentin in the Treatment of HBeAg-positive Chronic Hepatitis B / 中国药房

OBJECTIVE:To observe the clinical efficacy and safety of recombinant human interferon α2b (rhIFN α2b) combined with bozhi glycopeptides or thymopentin in the treatment of chronic hepatitis B (CHB).METHODS:Ninety HBeAg-positive CHB patients were selected from our hospital during Jan.2014-Jan.2015 and then randomly divided into group A,B,C,with 30 cases in each group.Group A was given rhINF α2b for injection (Pseudomonas) 5 million IU subcutaneously,qod;group B was additionally given Bozhi glycopeptides injection 4 mL added into 5％ Glucose injection 250 mL,ivgtt,qd,on the basis of group A;group C was additionally given Thymopentin for injection 2 mg added into 5％ Glucose injection 250 mL,ivgtt,qd,on the basis of group A.Three groups were treated for 24 weeks.The rate of ALT recovering to normal,negative rate of HBeAg,transformation rate of HBeAg/anti-HBeAg serum,negative rate of HBV-DNA and the decrease of HBsAg and HBV-DNA were compared among 2 groups after 4,8,12,24 weeks of treatment.The occurrence of ADR was recorded.RESULTS:After 4,8,12 weeks of treatment,there was no statistical significance in the rate of ALT recovering to normal,negative rate of HBeAg,transformation rate of HBeAg and the decrease of HBsAg among 3 groups (P＞0.05).After 4 weeks,negative rate of HBV-DNA in group B,C were significantly higher than group A;the decrease of HBV-DNA in group C were more significant than group A and B,with statistical significance (P＜0.05).After 8,12 weeks of treatment,the negative rate of HBV-DNA and the decrease of HBV-DNA in group B,C were significantly higher than group A,with statistical significance (P＜0.05);but there was no statistical signifi cance between group B and C (P＞0.05).After 24 weeks of treatment,there was no statistical significance in the rate of ALT recovering to normal,transformation rate of HBeAg,the decrease of HBsAg and negative rate of HBsAg among 3 groups (P＞0.05).The negative rate of HBsAg,negative rate of HBV-DNA and the decrease of HBV-DNA in group B,C were significantly higher than group A,with statistical significance (P＜0.05);there was no statistical significance between group B and C (P＞0.05).There was no statistical significance in the incidence of ADR among 3 groups(P＞0.05).CONCLUSIONS:rhIFN α2bcombined with bozhi glycopeptides or thymopentin shows good inhibitory effect on CHB,therapeutic efficacies of them are similar in the rate of ALT recovering to normal,but transformation rate of HBeAg,the decrease of HBsAg and negative rate of HBeAg.

Pacientes colonizados con Enterococcus faecalis VanB, internalizados en el Hospital Universitario "Luis Razetti", Barcelona, Venezuela

Durante los meses de febrero a julio de 2007, se muestrearon 57 pacientes hospitalizados en los servicios de UCI (Unidad cuidados Intensivos) y HD (Hemodiálisis), en la búsqueda de colonizados para Enterococcus resistentes a glucopéptidos. Veintiuno (14 de UCI y 7 de HD) hidrolizaron la esculina y crecieron en presencia de 6 µg/mL de vancomicina. Las principales especies de Enterococcus aisladas fueron: E. gallinarum, E. casseliflavus y E. faecalis. Las CMI de vancomicina estuvieron en un rango entre 2 y 16 mg/L y la CMI modal de las cepas estudiadas fue 8 mg/L. Hubo una prevalencia de 7 % de E. faecalis vanB.

During February and July of 2007, 57 inpatients of Intensive Care Unit and Hemodialyze were swabbed searching glycopeptides-resistant Enterococcus colonized. Twenty one (14 of ICU and 7 of HD) hydrolyzed sculin and grew on vancomycin 6 µg/ml. Main species were E. gallinarum, E. casseliflavus and E. faecalis. Vancomycin MICs were between 2 and 16 mg/l and MIC modal was 8 mg/l. Prevalence of vanB E. faecalis was 7 %.

Correlation between plasma copeptin levels and outcomes in patients with acute ischemic stroke / 国际脑血管病杂志

Objective To investigate the relationship between the serum copeptin levels and the outcomes in patients with acute ischemic stroke.Methods Patients with first-ever ischemic stroke within 24 h were enrolled in the study.Enzyme-linked immunosorbent assay was used to detect the serum copeptin levels.The National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the severity of baseline stroke.The modified Rankin Scale (mRS) scores were used to evaluate the outcomes at day 90,and 0-2 was defined as good outcome.The age-and sex-matched healthy subjects were used as controls.Results A total of 86 consecutive patients with first-ever ischemic stroke within 24 h were enrolled and 50 age-and.sex-matched healthy subjects were used as controls.The serum copeptin levels of the patients with acute ischemic stroke at 24 h,day 7 and 14 were 7.81 ± 0.66 pmol/L,4.78 ± 1.76 pmol/L,and 2.82 ± 1.42 pmol/L,respectively.They were all significantly higher than those of the control group (1.67 ± 0.56 pmol/L;all P＜0.05).In 86 patients,74 (86.05％) had good outcome and 12 (13.95％) had poor outcome.The age (67.64 ± 9.62 years vs.61.12± 7.31 years;t=-3.420,P=0.020),NIHSS score (14.16±4.22 vs.6.96± 2.04;t=-8.263,P＜ 0.001),baseline systolic blood pressure (166.06± 13.42 mmHgvs.154.12± 11.69 mmHg;t=5.216,P=0.037;1 mmHg=0.133 kPa),fasting blood glucose (8.79 ±2.98 mmol/L vs.6.92 ±2.24 mmol/L;t =2.076,P =0.041),C-reactive protein (7.02 ± 1.72 mg/L vs.4.07 ± 1.58 mg/L;t =-1.724,P =0.019),copeptin level at 24 h (9.67 ±2.28 pmol/L vs.6.88 ±2.82 pmol/L;t =13.962,P ＜ 0.001),copeptin level at day 7 (8.22 ± 2.14 pmol/L vs.2.97 ± 2.04 pmol/L;t =20.564,P ＜ 0.001),copeptin level at day 14 (4.77 ± 1.86 pmol/L vs.2.02 ± 0.76 pmol/L;t =8.428,P =0.032),as well as the proportions of atrial fibrillation (33.33％ vs.8.11％;x2 =4.986,P=0.036),large artery atherosclerotic stroke (41.67％ vs.21.62％;x2 =6.729,P =0.038),cardioembolism (33.33％ vs.8.11％;x2 =4.986,P=0.036) in the poor outcome group were significantly higher than those in the good outcome group.The proportion of patients with small arterial occlusive stroke was significantly lower than that of the good outcome group (16.67％ vs.70.27％;x2 =16.972,P =0.041).Multivariate logistic regression analysis showed that the serum copeptin level at 24 h (odds ratio 2.424,95％ confidence interval 1.92 0-3.562;P ＜ 0.001) and day 7 (odds ratio 2.326,95％ confidence interval 1.768-3.482;P ＜ 0.001),and baseline NIHSS score (odds ratio 2.146,95％ confidence interval 1.616-3.268;P ＜ 0.001) were the independent risk factors for the poor outcomes.Conclusions The increased baseline serum copeptin level is an independent risk factor for poor outcomes at day 90 in patients with acute ischemic stroke.

Bibliometric Analysis on Clinical Application of Bozhi Glycopeptides / 中国药师

Objective:To analyze the clinical application of Bozhi glycopeptides to provide reference for its rational use in clinics . Methods:The related literatures of Bozhi glycopeptides from the databases of CNKI , Wanfang and VIP were retrieved .The main clinical application ( the number of literatures on the same disease entities was above 3) and ADR were analyzed and evaluated .Results:A total of 163 literatures were found, including 137 clinical application and 11 ADR case reports.The disease with the number of literatures a-bove 3 included condyloma acuminatum (9 literatures), herpes zoster (6 literatures), hand-foot-mouth disease (6 literatures), psoriasis vulgaris (6 literatures), lung cancer (5 literatures), repeated respiratory infection (4 literatures) and hepatitis B (9 literatures), and the total number was 45.Among them, 32 literatures (1 772 cases) involved ADR, and 49 cases (2.77%) of ADR were reported, and the main performance was skin and its appendages damage (10 cases, 20.0%).Totally 11 ADR case reports mainly involved rigors and fever (13 cases, 37.2%).Conclusion:Bozhi glycopeptides as an adjuvant drug is mainly combined with other drugs to enhance the effi -cacy of mian drugs in clinical application , which shows low incidence of ADR mainly including skin and its appendages damage .

Clinical Usefulness of Arbekacin

Arbekacin is a broad-spectrum aminoglycoside used to treat methicillin-resistant Staphylococcus aureus (MRSA). Arbekacin has antibacterial activities against high-level gentamicin-resistant Enterococci, multidrug-resistant Pseudomonas aeruginosa, and Acinetobacter baumannii et al. Here, we reviewed in vitro data on arbekacin in Staphylococci and Gram-negative microorganisms. We also reviewed clinical studies for clinical efficacy and microbiologic efficacy data in patients with identified MRSA and suspected MRSA infections. The overall clinical efficacy ranged from 66.7% to 89.7%. The microbiologic efficacy rate ranged from 46.2% to 83%. In comparative studies between arbekacin and glycopeptides, arbekacin was similar to other glycopeptides with respect to clinical and microbiological efficacy rates. Combination trials with other antibiotics suggest that arbekacin will be a promising strategy to control Enterococcus spp. multi-drug resistant P. aeruginosa. The major adverse reaction was nephrotoxicity/hepatotoxicity, but patients recovered from most adverse reactions without any severe complications. Based on these results, arbekacin could be a good alternative to vancomycin/teicoplanin in MRSA treatment. Finally, therapeutic drug monitoring is recommended to maximize clinical efficacy and decrease nephrotoxicity.

Predictive value of plasma copeptin level for the outcomes in patients with acute ischemic stroke / 国际脑血管病杂志

Objective To investigate the predictive value of plasma copeptin level for the outcomes in patients with acute ischemic stroke. Methods Consecutive patients with acute ischemic stroke were enroled in the study. Enzyme-linked immunosorbent assay was used to detect the plasma copeptin level. The National Institutes of Health Stroke Scale (NIHSS) was used to evaluate baseline stroke severity. The outcome was evaluated at 90 days with the modified Rankin Scale (mRS), and the good outcome was defined as mRS 0 - 2. Results A total of 160 patients with acute ischemic stroke were enroled, 121 had good outcome and 39 had poor outcome. The age (71. 87 ± 6. 11 years vs. 66. 19 ± 9. 39 years; t =- 3. 540, P = 0. 001), serum levels of C-reactive protein (6. 84 ± 2. 80 mmol/L vs. 5. 84 ± 2. 89 mmol/L;t = - 2. 459, P = 0. 023) and copeptin (143. 12 ± 34. 02 pmol/L vs. 50. 78 ± 18. 62 pmol/L; t = 21. 564, P 104. 3 pmol/L was used as the cutoff value, the sensitivity and specificity for predicting the poor outcomes at day 90 after onset were 86. 8% and 40. 2% , respectively. Conclusions The plasma copeptin level may be a good predictor for neurological outcome at day 90 after onset in patients with acute ischemic stroke.

Factors associated with Clostridium difficile diarrhea in a hospital in Beijing, China

Clostridium difficile is the most common cause of hospital-acquired diarrhea in patients treated with antibiotics, chemotherapeutic agents, and other drugs that alter the normal equilibrium of the intestinal flora. A better understanding of the risk factors for C. difficile-associated disease (CDAD) could be used to reduce the incidence of CDAD and the costs associated with its treatment. The aim of this study was to identify the risk factors for CDAD in a cohort of Chinese patients in a Beijing hospital. Medical charts of a total of 130 inpatients (62 males and 68 females) with hospital-acquired diarrhea (45 with CDAD; 85 without CDAD) were retrospectively reviewed. C. difficile toxins A and B were detected in fecal samples using enzyme-linked fluorescence assays. The drugs used by patients with and without CDAD before the onset of diarrhea were compared. Factors that differed significantly between the two groups by univariate analysis were analyzed by multivariate analysis using a logistic regression model. Multivariate analysis showed that cephalosporin treatment was associated with a significantly higher risk of CDAD in hospitalized patients, while treatment with glycopeptides was significantly associated with a reduction in CDAD (P<0.001 for cephalosporin; P=0.013 for glycopeptides). Our data confirmed previous findings that empirical treatment with cephalosporins is positively associated with CDAD compared to individuals using other CDAD-related drugs. Additionally, we showed that treatment with glycopeptides was negatively associated with CDAD, compared to individuals using other CDAD-related drugs.

C-terminal provasopressin measurement and cardiovascular disease / 中华检验医学杂志

Copeptin,the C-terminal portion of provasopressin,is a novel neurohormone of the arginine vasopressin (AVP)system,and is known to be co-released with AVP from hypothalamus.As a surrogate marker of the AVP system,copeptin has gradually replaced AVP in several clinical studies largely due to its structural and methodological advantages.Copeptin has been regarded as a marker of non-specific stress response.In recent years,copeptin attracts more and more attention especially in cardiovascular conditions (heart failure and acute coronary syndromes).The present review primarily focuses on copeptin detection,its general advantages,and its potential clinical value in a variety of cardiovascular conditions.

Neuroendocrine biomarkers of ischemic stroke / 国际脑血管病杂志

At present,stroke has become one of the diseases seriously harming the human life and the quality of life with its high morbidity,disability,and mortality.Therefore,clinicians need to find more effective indicators to identify the clinical conditions and outcomes,and guide the treatment.Studies in recent years have suggested that the biological markers have important clinical value for guiding the treatment of stroke.

Evaluación de la susceptibilidad a glicopéptidos en cepas de Staphylococcus aureus resistentes a oxacilina / Evaluation of susceptibility to glycopeptides in oxacillin resistant Staphylococcus aureus strains

Candida albicans y Candida dubliniensis presentan una estrecha relación filogenética. La similitud de estas especies puede hacer que en un laboratorio microbiológico se identifique en forma errónea C. dubliniensis como C. albicans. El objetivo de esta investigación fue evaluar diversos métodos fenotípicos para la diferenciación entre Candida dubliniensis y Candida albicans. Se utilizaron 6 cepas control de C. dubliniensis y una de C. albicans, provenientes de colecciones reconocidas y sometidas a genotipificación. También se utilizaron 70 aislados identificados como posibles C. albicans utilizando el medio CHROMagar Candida y el medio de bilis agar Feo. Los métodos evaluados fueron: agar Sabouraud dextrosa a 45°C, agar Sabouraud con NaCl al 6,5%, agar Tween 80, agar tabaco, agar Pal’s, agar tomate-zanahoria y aglutinación con partículas de látex (Bichro-Dubli Fumouze®). Encontramos que las técnicas más confiables para realizar la diferenciación fenotípica entre estas dos especies fueron: el agar tomate-zanahoria, el agar Pal’s, el agar tabaco y la aglutinación con partículas de látex (Bichro-Dubli Fumouze®). Además en este estudio, de los 70 aislados considerados como C. albicans, encontramos 1 (1.4%) posible Candida dubliniensis. Sin embargo, las pruebas de biología molecular son las más adecuadas para el diagnóstico certero de estas dos especies.

Candida albicans and Candida dubliniensis have a close phylogenetic relationship. The similarity between these species can cause a microbiology laboratory to identify C. dubliniensis erroneously as C. albicans. The objective of this research was to evaluate diverse phenotypic methods for differentiating between Candida dubliniensis and Candida albicans. Six control strains of C. dubliniensis and one of C. albicans from recognized collections were used and submitted to genotypification. Also, 70 isolates were used, identified as possible C. albicans utilizing CHROMagar Candida and bilis agar Feo mediums. The methods evaluated were: Sabouraud dextrosa agar at 45°C, Sabouraud agar with NaCl at 6.5%, Tween 80 agar, tobacco agar, Pal’s agar, tomato-carrot agar and agglutination with latex particles (Bichro-Dubli Fumouze®). It was found that the most reliable techniques for performing phenotype differentiation between these two species were tomato-carrot agar, Pal’s agar, tobacco agar and agglutination with latex particles (Bichro-Dubli Fumouze®). Of the 70 isolates considered to be C. albicans, one (1.4%) possible Candida dubliniensis was found. Nevertheless, molecular biology tests are the most appropriate means for achieving an accurate diagnosis of these two species.

Mecanismos de resistencia a gliocopéptidos en Staphylococcus aureus / Mechanisms of resistance to glycopeptides in Staphylococcus aureus

Los glicopéptidos (vancomicina y teicoplanina) constituyen una alternativa terapéutica en el tratamiento de infecciones severas por cepas de S. aureus resistentes a meticilina. Sin embargo, ya se han descrito dos mecanismos de resistencia en S. aureus: resistencia de bajo nivel, caracterizada por un engrosamiento anormal de la pared celular, presente en las cepas VISA y, resistencia de alto nivel mediada por el operón vanA, que provoca la sustitución de los residuos terminales D-ala-D-ala por D-ala-D-lac, disminuyendo su afinidad por el antibiótico. Esta revisión resume la historia de la aparición de la resistencia a glicopéptidos en S. aureus y considera los mecanismos que determinan la resistencia en estos organismos como base para comprender la necesidad y los potenciales roles de nuevos agentes de esta clase

Glycopeptides (vancomycin and teicoplanin) are an alternative therapeutic in the treatment of severe infections by methicillin-resistant S. aureus strains. However, two resistance mechanisms of S. aureus have already been described: low-level resistance, characterized by an abnormal thickening of the cellular wall, present in the VISA strains, and high-level resistance, mediated by the vanA operon, which causes the replacement of D-ala - D-ala terminal residues by D-ala-D-lac, decreasing its affinity for the antibiotic. This review summarizes the history of the emergence of glycopeptide resistance in S. aureus and considers the mechanisms that determine the resistance in these organisms as a background for understanding the need and potential roles of new agents of this kind

Copeptin: a novel prognostic marker for cerebrovascular disease / 国际脑血管病杂志

Copeptin is a part of the C-terminal pro-arginine vasopressin. It is correlated with the prognosis of various diseases. Recent studies have found that copeptin is a novel,independent prognostic marker for stroke, and it may improve the existing risk stratification scheme of stroke.

Effect of Ganoderma lucidum polysaccharides peptide on invasion of human lung carcinoma cells in vitro / 北京大学学报(医学版)

Objective:To find out the effects of Ganoderma lucidum polysaccharides peptide (Gl-PP) on the invasion of the human lung carcinoma cell (PG cell). Methods: PG cells were pretreated with different concentration Gl-PP in vitro, using cell proliferation assay, cell migration assay, adhesion assay, zymography and RT-PCR, then the effects of Gl-PP on proliferation, motility, adhesion and MMP-9 activity and mRNA expression of PG cells were investigated in vitro. Results: Gl-PP did not directly inhibit PG cell proliferation in vitro. However, pretreated with Gl-PP, PG cells motility was inhibited significantly. PG cells adhesion was also inhibited. The activity of MMP-9 was inhibited in a dose-dependent manner, and the inhibited ratio was 41.53% at a dose of 100 mg/L Gl-PP. The mRNA expression of MMP-9 of pretreated PG cells was inhibited. Conclusion: Gl-PP could suppress invasion of human lung carcinoma cells in vitro.

Influence of Glycopeptides, as a Risk Factor on Intestinal Colonization with Vancomycin-Resistant Enterococcus / 대한임상미생물학회지

BACKGROUND: Several risk factors related with vancomycin-resistant Enterococcus (VRE) colonization are well known, but the direct relatedness of the use of glycopeptides with VRE colonization is not confirmed yet. So we evaluated the influence of the use of glycopeptides and other variables, as risk factors on intestinal colonization with VRE. METHODS: In glycopeptide-administered inpatients group, multiple stool specimens were collected on the day of glycopeptides administration, and weekly after that, until VRE were detected. In the inpatients and outpatients control groups, stool were obtained with point survey. The specimens were inoculated on m-enterococcus agar with 6mg/L vancomycin. The phenotypes and genotypes of resistance of the VRE isolates were confirmed by disk diffusion and agar dilution tests, and polymerase chain reaction. RESULTS: Of the 361 patients(530 specimens), twelve VRE(3.3%) were isolated. The rates of intestinal colonizations were not significantly differed between the inpatients groups with or without glycopeptides administration, which are 5.1 and 4.1%, respectively. The colonization rates were significantly higher in the patients with 30 or more hospital stay, and in those with three or more antimicrobial administrations. vanA and vanC genes were amplified in the isolates. CONCLUSIONS: It is demonstrated that the use of glycopeptides is not a direct risk factor of intestinal colonization of VRE in Pusan National University Hospital, in which the prescription of glycopeptides is rigidly controlled. But, a shortened stay in the hospital will diminish the intestinal colonization of VRE.