Peptide dual agonists toward both glucagon-like peptide 1 receptor (GLP-1R) and glucagon receptor (GCGR) are emerging as novel therapeutics for the treatment of type 2 diabetes mellitus (T2DM) patients with obesity. Our previous work identified a Xenopus GLP-1-based dual GLP-1R/GCGR agonist termed xGLP/GCG-13, which showed decent hypoglycemic and body weight lowering activity. However, the clinical utility of xGLP/GCG-13 is limited due to its short in vivo half-life. Inspired by the fact that O-GlcNAcylation of intracellular proteins leads to increased stability of secreted proteins, we rationally designed a panel of O-GlcNAcylated xGLP/GCG-13 analogs as potential long-acting GLP-1R/ GCGR dual agonists. One of the synthesized glycopeptides 1f was found to be equipotent to xGLP/GCG-13 in cell-based receptor activation assays. As expected, O-GlcNAcylation effectively improved the stability of xGLP/GCG-13 in vivo. Importantly, chronic administration of 1f potently induced body weight loss and hypoglycemic effects, improved glucose tolerance, and normalized lipid metabolism and adiposity in both db/db and diet induced obesity (DIO) mice models. These results supported the hypothesis that glycosylation is a useful strategy for improving the in vivo stability of GLP-1-based peptides and promoted the development of dual GLP-1R/GCGR agonists as antidiabetic/antiobesity drugs.
Mice ; Animals ; Glucagon-Like Peptide 1/metabolism* ; Receptors, Glucagon/therapeutic use* ; Xenopus laevis/metabolism* ; Diabetes Mellitus, Type 2/drug therapy* ; Glycopeptides/therapeutic use* ; Obesity/drug therapy* ; Hypoglycemic Agents/pharmacology* ; Peptides/pharmacology*

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.
Animals ; Chromatography, Liquid ; Deer ; Gelatin ; Glycopeptides ; Tandem Mass Spectrometry

Annual proficiency surveys were conducted in March, June, and September in 2015 by the Clinical Microbiology Subcommittee of the Korean Association of External Quality Assessment Service. The program covers the sections of bacteriology, advanced bacteriology and mycology, mycobacteriology, and parasitology. Each trial was composed of three sets of different combinations of five bacteria and yeasts. These sets were distributed among laboratories for Gram staining, culture, identification, and antimicrobial susceptibility tests. Five slides with fixed sputum smears were provided as part of each trial for acid-fast bacilli detection. The survey material distribution was section-based. Two survey materials were provided in each trial, while five specimens for mycobacterial culture and identification, five specimens for anti-tuberculosis susceptibility testing and two Mycobacterium tuberculosis strains for rapid detection of rifampin and isoniazid resistance were distributed in the March and June trials. Five virtual microscopy files for stool parasite examination were availed by registered participants in the June trial. Out of the 334 enrolled laboratories, 328 (98.2%), 328 (98.2%), and 329 (98.5%) submitted responses in trials I, II, and III, respectively. Identification of bacteria, namely, Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Pseudomonas aeruginosa, Streptococcus pneumoniae, and Vibrio fluvialis by more than 95% of participants was acceptable. Surveillance cultures for vancomycin-resistant enterococci and carbapenem-resistant Enterobacteriaceae were determined accurately by 75.8%–85.3% and 93.1% of the respondents, respectively. Species-level identification of Candida krusei, Candida lusitanae, and Candida guilliermondii was still low at 79.8%, 55.7%, and 42.7%, respectively. Disk diffusion method revealed an unacceptably high false-positive rate of resistance to glycopeptides in E. faecalis and to trimethoprim-sulfamethoxazole in S. pneumoniae. Advanced bacteriology trials revealed unsatisfactory results for species-level identification of moulds. Mycobacterial culture, identification and susceptibility testing, and molecular detection of rifampin and isoniazid resistance were performed exceedingly well by participants. Hymenolepsis diminuta could not be identified by participants, with a correct answer rate of only 46.5% and ‘no parasite seen’ answer rate of only 31.8% for negative specimens. Species-level identification of Candida and moulds was challenging for clinical microbiology laboratories. Disk diffusion method was found to be problematic in testing the susceptibility of microorganisms to glycopeptides and trimethoprim-sulfamethoxazole. Improvement is required in result interpretation of negative specimens in parasitology.
Bacteria ; Bacteriology ; Candida ; Diffusion ; Enterobacteriaceae ; Enterococcus faecalis ; Escherichia coli ; Glycopeptides ; Isoniazid ; Klebsiella pneumoniae ; Korea* ; Methods ; Microscopy ; Mycobacterium ; Mycobacterium tuberculosis ; Mycology ; Parasites ; Parasitology ; Pneumonia ; Pseudomonas aeruginosa ; Quality Control ; Rifampin ; Sputum ; Streptococcus pneumoniae ; Surveys and Questionnaires ; Trimethoprim, Sulfamethoxazole Drug Combination ; Vancomycin-Resistant Enterococci ; Vibrio ; Yeasts

PURPOSE: The incidence of adverse drug reactions (ADRs) is increasing. However, studies on the prevalence of ADRs in children are rare. The aim of this study was to investigate the causative drugs and clinical features of ADRs for children in a tertiary university hospital of Korea. METHODS: We retrospectively collected ADRs by a computerized self-reporting system in Asan Medical Center. ADRs of children under the age 18 were collected from January 2005 to August 2015, and we analyzed only ADRs containing current symptoms among total ADR data. RESULTS: A total of 1,408 ADR cases were reported, There were 764 male (54.3%) and 644 female patients (45.7%), and the mean age was 11.5±5.8 years (range, 0–18 years). Antibiotics (n=479, 34.0%) were the most common causative drugs, followed by tramadol (n=173, 12.3%), nonsteroidal anti-inflammatory agents (NSAIDs) and acetylsalicylic acid (n=103, 7.3%), narcotics (n=91, 6.5%), antineoplastics (n=87, 6.2%), and sedatives (n=82, 5.8%). The most common clinical features were skin manifestations (n=500, 34.4%). Gastrointestinal symptoms (n=435, 29.9%) were the second most common clinical features, followed by neuropsychiatric symptoms (n=155, 10.7%) and respiratory symptoms (n=123, 8.5%). Among antibiotics, glycopeptides (n=110, 23.0%), third-generation cephalosporins (n=83, 17.3%), and penicillin/β-lactamase inhibitors (n=60, 12.7%) were the most frequently reported causative drugs. CONCLUSION: Antibiotics were the most reported common causative drugs of ADRs in children, followed by tramadol, NSAID, and narcortics. Compared with adults, the prevalence of contrast medium-induced ADR was lower in children with a higher prevalence of sedative-associated ADR. Greater attention to possible ADRs in children is needed among medical personnel.
Adult ; Anti-Bacterial Agents ; Anti-Inflammatory Agents, Non-Steroidal ; Antineoplastic Agents ; Aspirin ; Cephalosporins ; Child ; Chungcheongnam-do ; Drug-Related Side Effects and Adverse Reactions* ; Female ; Glycopeptides ; Humans ; Hypnotics and Sedatives ; Incidence ; Korea ; Male ; Narcotics ; Prevalence ; Retrospective Studies ; Skin Manifestations ; Tramadol

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.
Acinetobacter baumannii ; Anti-Bacterial Agents ; Drug Monitoring ; Enterococcus ; Glycopeptides ; Humans ; Methicillin-Resistant Staphylococcus aureus ; Pseudomonas aeruginosa

Rothia muciliaginosa (R. mucilaginosa) is a facultative, Gram-positive coccus that is considered to be part of the normal flora of the mouth and respiratory tract. There are sporadic reports of the organism causing endocarditis in patients with heart valve abnormalities, as well as meningitis, septicemia, and pneumonia associated with intravenous drug abuse. However, it is an unusual pathogen in cases of peritoneal dialysis (PD)-associated peritonitis. Although R. mucilaginosa is generally susceptible to penicillin, ampicillin, cefotaxime, imipenem, rifampicin, and glycopeptides, there are no guidelines for the treatment of PD-associated peritonitis. Herein, we report a case of PD-associated peritonitis due to R. mucilaginosa that was resolved with intraperitoneal antibiotic treatment.
Ampicillin ; Cefotaxime ; Endocarditis ; Glycopeptides ; Heart Valves ; Humans ; Imipenem ; Meningitis ; Mouth ; Penicillins ; Peritoneal Dialysis ; Peritoneal Dialysis, Continuous Ambulatory ; Peritonitis* ; Pneumonia ; Respiratory System ; Rifampin ; Sepsis ; Substance Abuse, Intravenous

BACKGROUND: Patients infected with vancomycin-resistant enterococci (VRE) are kept in isolation to prevent the spread of VRE in medical facilities. However, decision-making regarding isolation can be challenging at the time of re-admission of previously VRE-colonized or infected patients who have not been examined for VRE infections for a long time. This study focused on providing guidelines for isolating VRE patients based on the analysis of risk factors for prolonged carriage and reacquisition of VRE. METHODS: A retrospective review was performed on medical records of patients who were diagnosed with VRE infections at a university hospital in 2009. Durations of colonization and negative conversion of VRE were estimated by Kaplan-Meier methods. Prolonged duration of VRE infections and risk factors for reacquisition were analyzed using Cox's proportional hazard model. RESULTS: Among 220 VRE-colonized patients, 132 were cleared, and 30 reacquired after negative conversion of VRE. The median duration of colonization was 33.1 weeks, and the median clearance period was 19.4 weeks. Patients who were admitted via the emergency department and treated with glycopeptides tended to have prolonged duration of VRE colonization. Prolonged hospitalization and metronidazole therapy increased the risk of reacquisition more rapidly. CONCLUSION: Treatment with glycopeptides, metronidazole antibiotic therapy, history of admission via the emergency department, and prolonged hospitalization can affect to prolonged carriage and reacquisition of VRE. Consider carefully the release of isolation of VRE patients with these risk factors.
Colon ; Emergency Service, Hospital ; Enterococcus ; Glycopeptides ; Hospitalization ; Humans ; Medical Records ; Metronidazole ; Patient Isolation ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors* ; Vancomycin Resistance

PURPOSE: Copeptin has been considered as a useful marker for diagnosis and prediction of prognosis in heart diseases. However, copeptin has not been investigated sufficiently in hemodialysis patients. This study aimed to investigate the general features of copeptin in hemodialysis and to examine the usefulness of copeptin in hemodialysis patients with left ventricular dysfunction (LV dysfunction). MATERIALS AND METHODS: This study included 41 patients on regular hemodialysis. Routine laboratory data and peptides such as the N-terminal of the prohormone brain natriuretic peptide and copeptin were measured on the day of hemodialysis. Body fluid volume was estimated by bioimpedance spectroscopy, and the E/Ea ratio was estimated by echocardiography. RESULTS: Copeptin increased to 171.4 pg/mL before hemodialysis. The copeptin had a positive correlation with pre-dialysis body fluid volume (r=0.314; p=0.04). The copeptin level decreased along with body fluid volume and plasma osmolality during hemodialysis. The copeptin increased in the patients with LV dysfunction more than in those with normal LV function (218.7 pg/mL vs. 77.6 pg/mL; p=0.01). Receiver operating characteristic curve analysis showed that copeptin had a diagnostic value in the hemodialysis patients with LV dysfunction (area under curve 0.737; p=0.02) and that the cut-off value was 125.48 pg/mL (sensitivity 0.7, specificity 0.8, positive predictive value 0.9, negative predictive value 0.6). CONCLUSION: Copeptin increases in hemodialysis patients and is higher in patients with LV dysfunction. We believe that copeptin can be a useful marker for the diagnosis of LV dysfunction in hemodialysis patients.
Adult ; Aged ; Biomarkers/blood ; Echocardiography ; Female ; Glycopeptides/*blood ; Humans ; Kidney Failure, Chronic/*blood/complications/therapy ; Male ; Middle Aged ; Natriuretic Peptide, Brain/blood ; Predictive Value of Tests ; Prognosis ; ROC Curve ; Renal Dialysis/*adverse effects ; Sensitivity and Specificity ; Ventricular Dysfunction, Left/*blood/complications/*physiopathology

OBJECTIVETo assess the value of combined detection of copeptin and ischemia modified albumin (IMA) in early diagnosis and prognostic evaluation of myocardial damage in patients with acute organic phosphorus pesticide poisoning (AOPP).

METHODSA total of 126 AOPP patients were examined for blood copepin and IMA levels and myocardial injury markers within 1 h after admission.

RESULTSCopeptin and IMA levels significantly increased in patients with AOPP compared with those in the control subjects. Copeptin and IMA levels were significantly higher in severe AOPP cases than in mild to moderate cases (P<0.05). Logistic regression analysis showed that increased copeptin and IMA levels and severe complications of AOPP were associated with an increased risk of cardiovascular events.

CONCLUSIONEarly detection of copeptin and IMA levels has important clinical value in early diagnosis and prognostic evaluation of myocardial damage in patients with AOPP, and their levels are positively correlated with the severity of the condition.

Biomarkers ; blood ; Early Diagnosis ; Glycopeptides ; blood ; Humans ; Organophosphate Poisoning ; diagnosis ; Pesticides ; poisoning ; Prognosis ; Serum Albumin ; Serum Albumin, Human

Glycopeptides of the clinically important antibiotic drugs are glycosylated cyclic or polycyclic nonribosomal peptides. Glycopeptides such as vancomycin and teicoplanin are often used for the treatment of gram-positive bacteria in patients. The increased incidence of drug resistance and inadequacy of these therapeutics against gram-positive bacterial infections would be the formation and clinical development of more variable second generation of glycopeptide antibiotics: semisynthetic lipoglycopeptide analogs such as telavancin, dalbavancin, and oritavancin with improved activity and better pharmacokinetic properties. In this review, we describe the development of and bacterial resistance to vancomycin, teicoplanin, and semisynthetic glycopeptides (teicoplanin, dalbavancin, and oritavancin). The clinical influence of resistance to glycopeptides, particularly vancomycin, are also discussed.
Anti-Bacterial Agents* ; Drug Resistance ; Glycopeptides ; Gram-Positive Bacteria ; Gram-Positive Bacterial Infections ; Humans ; Incidence ; Peptides ; Teicoplanin ; Vancomycin