A novel synthetic hexapeptide (SFKLRY-NH2) that displays angiogenic activity has been identified by positional scanning of a synthetic peptide combinatorial library (PS-SPCL). This study was carried out to investigate the irritation of the SFKLRY-NH2 on the skin. The tests were performed on the basis of Korea Food and Drug Administration (KFDA) guidelines. In results, cell toxicity is not appeared for SFKLRY-NH2 in HaCaT cells and B16F10 cells. SFKLRY-NH2 induced no skin irritation at low concentration (10 microM), mild irritation at high concentration (10mM). We consider that this result is helpful for saying about the safety of SFKLRY-NH2 in clinical use.
Korea ; Oligopeptides ; Peptide Library ; Skin ; United States Food and Drug Administration

Aspargine-glycine-arginine (NGR)-containing peptides are targeted peptides which can be integrated with CD13 receptors on tumor vascular endothelial cells. NGR peptides are connected to liposomes to obtain NGR peptide-modified liposomes. By intravenous injection of these liposomes, NGR peptides can be combined with CD13 receptors on tumor vascular endothelial cells, position liposomes in tumor tissues, and concentrate drug in liposomes in tumor, so as to enhance the antitumor effect. The article starts with NGR peptides, summarizes definition of NGR, NGR peptide-modified liposomes, strengths and weaknesses of NGR peptide-modified liposomes in antitumor and the latest study orientation of NGR peptide-modified liposomes, and looks into the future of studies on NGR peptide-modified liposomes.
Animals ; Antineoplastic Agents ; pharmacology ; CD13 Antigens ; administration & dosage ; pharmacology ; Humans ; Liposomes ; Oligopeptides ; administration & dosage ; pharmacology

PURPOSE: Serious acetaminophen (AAP) poisoning causes hepatotoxicity. N-acetylcysteine (NAC) is the most effective therapy for AAP poisoning and can be administered orally and intravenously (IV). Several studies have compared the efficacy of these two routes of administration and the results have been controversial. The purpose of this study was to compare the efficacy of oral and IV NAC for the prevention of hepatic toxicity in Korean patients whose serum AAP levels were higher than normal. METHODS: A retrospective before/after study was performed, in which the patients presented to the emergency department with an AAP overdose from February 1995 to March 2012. A 3-day oral NAC regimen was used in the beginning, and a 20-hr intravenous regimen was then used from 2007. This study assessed the complications of an AAP overdose, such as hepatotoxicity, hepatic failure and renal failure as well as the side effects of the treatment regimen. RESULTS: A total of 41patients was enrolled in this study. The median ALT and AST were 63 (IU/L) and 57 (IU/L) for the oral NAC treated patients, and 14 (IU/L) and 20 (IU/L) for the IV NAC treated patients (p=0.004 and p=0.001, respectively). The incidence of complications was similar in the treatment groups (p=0.399). Among the patients, 7 patients developed hepatotoxicity and were treated successfully with oral or IV NAC. CONCLUSION: This study suggests that IV NAC and oral NAC can prevent and successfully treat hepatic toxicity in patients whose serum AAP levels are higher than normal.
Acetaminophen ; Acetylcysteine ; Administration, Intravenous ; Emergencies ; Humans ; Incidence ; Liver Failure ; Oligopeptides ; Renal Insufficiency ; Retrospective Studies

OBJECTIVETo evaluate the efficacy and safety of telaprevir combined with peginterferon alfa (Peg-IFNa) plus ribavirin (RBV) (collectively, TPR therapy) in patients with chronic hepatitis C (CHC) using a meta-analysis approach.

METHODSThe Pubmed literature database was searched for randomized controlled trials of TRP therapy in CHC patients published between 2009 and 2011. The following outcome data was extracted for meta-analysis of efficacy: sustained virological response (SVR), defined as serum HCV RNA of less than 1000 copies/ml at end-of-treatment (week 24); rapid virological response (RVR), defined as serum HCV RNA of less than 1000 copies/ml at treatment week 4; recurrence, defined as serum HCV RNA of less than 1000 copies/mL at end-of-treatment and more than 1000 copies/ml at follow-up (week 24 after treatment completion). The pooled odds ratio (OR) or relative risk (RR) were calculated, with 95% confidence interval (CI). Heterogeneity was assessed by the Chi-squared test based on the Q statistic.

RESULTSSix studies of TPR triple therapy, representing a total of 2677 CHC patients, were included in the meta-analysis. Among the 1850 patients who received TPR, 56.3% (n = 1041) achieved RVR, 66.8% (n = 1235) achieved SVR, and 12.1% (n = 176/1460) experienced recurrence. Among the 827 patients who received PR double-therapy, 7.0% (n = 58) achieved RVR, 35.8% (n = 296) achieved SVR, and 32.3% (n = 145/449) experienced recurrence. The TRP group had significantly higher rates of RVR (OR = 29.83, 95% CI: 16.16 to 55.05) and SVR (OR = 3.97, 95% CI: 2.58 to 6.11) than the PR group (both P less than 0.01), and significantly lower rate of recurrence (RR = 0.36, 95% CI: 0.24 to 0.56, P less than 0.01).

CONCLUSIONThe therapeutic effect of research group is better than that of control group, suggesting that ornithine aspartate combined with naloxone treatment in hepatic encephalopathy is worthy of promoting.

Drug Therapy, Combination ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferon-alpha ; administration & dosage ; therapeutic use ; Oligopeptides ; administration & dosage ; therapeutic use ; Ribavirin ; administration & dosage ; therapeutic use ; Treatment Outcome

Using a simple method to determine the interaction between peptide and lipid bilayer and then deciding how to modify formulation from classic DepoFoam technology, multivesicular liposome of LXT-101 (DepoLXT-101) was prepared and characterized by in vitro evaluation. The electrostatic adsorption between peptide and lipid bilayer was observed by zeta potential and fluorescence spectrum. Anionic surfactants were added to stable the multiple emulsion and minimize the opposite effects resulted from drug. Encapsulation efficiency was determined by RP-HPLC. Morphology, particle size of DepoLXT-101 particles were characterized and their in vitro release was studied in sodium chloride solution. The DepoLXT-101 particles were prepared with good encapsulation efficiency, narrow size distribution and multivesicular construction. Over 95% of the DepoLXT-101 particles were in a size range of 5-20 microm. The in vitro assay in sodium chloride solution at 37 degrees C showed that 70%-90% of the peptide was released from particles slowly over 11 days. Multivesicular liposome sustained delivery of synthetic cationic peptides could be successfully prepared by the method.
Delayed-Action Preparations ; Drug Compounding ; Drug Delivery Systems ; methods ; Gonadotropin-Releasing Hormone ; antagonists & inhibitors ; Liposomes ; administration & dosage ; pharmacokinetics ; Oligopeptides ; administration & dosage ; pharmacokinetics ; Particle Size ; Technology, Pharmaceutical ; methods

Animals ; Antineoplastic Agents ; administration & dosage ; Chemoembolization, Therapeutic ; methods ; Female ; Hepatic Artery ; Liver Neoplasms, Experimental ; therapy ; Oligopeptides ; administration & dosage ; Rats ; Rats, Wistar

The combination of atazanavir (ATV) and lopinavir/ritonavir (LPV/RTV) with nucleoside reverse transcriptase inhibitors (NRTI) has been used as a salvage regimen for human immunodeficiency virus (HIV)-positive patients. In this paper, we discuss two cases of HIV-positive patients who had long histories of virological failure following a heavy treatment of antiretroviral drugs, but then achieved virological suppression with double-boosted protease inhibitor (PI) regimens. In patients with multiple genotypic resistance to PIs and NRTIs, virological suppression can be achieved with a combination of ATV plus LPV/RTV with an NRTI backbone. The two cases in this report suggest that a combination of ATV plus LPV/RTV could be a useful salvage regimen for the subset of HIV-positive patients with limited treatment options.
Adult ; Drug Resistance, Multiple, Viral ; Drug Therapy, Combination ; HIV Infections/*drug therapy ; HIV Protease Inhibitors/*administration & dosage ; Humans ; Male ; Oligopeptides/*administration & dosage ; Pyridines/*administration & dosage ; Pyrimidinones/*administration & dosage ; Ritonavir/*administration & dosage

A novel fibrinolytic enzyme subtilisin FS33, which exhibits much higher activity for decomposing fibrin than urokinase, was purified from Douchi, a traditional soybean-fermented food in China. In order to increase bio-utilization and thrombus targetability of subtilisin FS33 labeled by fluorescein isothiocyanate (FITC), the surface modified liposomes encapsulating subtilisin FS33 and FITC with a synthetic peptide Arg-Gly-Asp-Ser (RGDS), being putatively a specific antagonist of fibrinogen receptor on platelet membrane, were prepared and used to evaluate the therapeutic efficacy in a rat model thrombotic carotid artery. The arterial thrombosis was induced by applying two pieces of filter paper (1 x 2 cm) saturated with 10% of ferric chloride (FeCl3). The rats were infused via the jugular vein with either liposomes carrying BSA (control group) or RGDS-liposomes carrying subtilisin FS33 at doses of 2000 and 4000 U/kg. The plasma of the group infused with RGDS-liposomes showed higher antithrombotic and fibrinolytic activity than did the control group within 15-120 min after infusing. The higher the dose was gived, the higher the activity was shown. APTT(activiated partial thromboplastin time), PT (prothrombin time) and TT (thrombin time) were extended remarkably (P < 0.05, P < 0.01), and FDP (fibrinogen degradation products) also increased greatly (P < 0.01), while ELT (euglobulinlysis time) decreased obviously (P < 0.05). FITC content in heart and brain evidently increased (P < 0.05), and results of D-dimer test were all positive. In addition, the venous thrombi in brain and kidney were dissolved totally or partly as observed by patholgical section. All these indicated that subtilisin FS33 enhanced the antithrombotic and fibrinolytic activities in rat, and RGDS-liposomes improved, in a certain degree, the thrombolytic specificity for targeting to thrombus.
Animals ; Carotid Artery Thrombosis ; drug therapy ; etiology ; Drug Carriers ; Drug Delivery Systems ; Female ; Fibrinolytic Agents ; administration & dosage ; Liposomes ; administration & dosage ; chemistry ; Male ; Oligopeptides ; administration & dosage ; chemistry ; Random Allocation ; Rats ; Rats, Wistar ; Subtilisins ; administration & dosage ; isolation & purification

Clinically, there has been so far no effective way to repair the bone-missing of large extent due to gash, infection and removal of tumor. The solution of this problem can be assisted by the addition of bioactive substances to substrate materials, because the growth of peripheral tissue and the fiber tissue growing the materials can be induced to the direction of bone-tissue by these biomaterials with bioactive peptides. The peptide Arg-Gly-Asp is the point between the integrin which comes from membrane and the ligand. In certain cases, the artificially synthesized RGD can be competitively combined with the integrin on cell surface, and outer-cell information is transmitted into cells, which will cause a series of physiological changes in cells. Presently, it is reported that the RGD has the ability to induce the growth of osteoblasts, restrain the adhesion between osteoclasts and substrates. This paper reviews and introduces the progress made with the work of RGD-inducing bone regeneration.
Biocompatible Materials ; Bone Regeneration ; drug effects ; physiology ; Cell Adhesion ; drug effects ; Oligopeptides ; administration & dosage ; chemistry ; pharmacology ; Osteoblasts ; drug effects ; physiology ; Osteoclasts ; drug effects ; physiology ; Tissue Engineering ; methods

OBJECTIVETo determine the inhibitory effects of BIO-1211, a very late antigen-4 (vla-4) antagonist, on bronchoconstriction and neutrophil adhesion in rats.

METHODSFor evaluating ovalbumin-induced bronchoconstriction in the sensitized rats, the changes in lung resistance (RL) and lung dynamic compliance (C(dyn)) were determined after antigen challenge. Neutrophils from the rats were used to determine fibronectin and serum-induced cell adhesion. The effect of BIO-1211 on wheezing was determined after inhalation of histamine and acetylcholine in guinea pigs.

RESULTBIO-1211 aerosol at 1, 3 and 10 mg/ml significantly inhibited the changes in lung resistance and lung dynamic compliance after antigen challenge in the sensitized rats in a dose-dependent manner. BIO-1211 at 25, 50, 100 and 200 microgram/ml inhibited the fibronectin-induced neutrophil adhesion by 23.5%, 24.6%, 61.4% and 58.1%, respectively, and serum-induced adhesion by 29.9%, 35.9%, 35.3% and 15.4%, respectively. Inhalation of 10 mg/ml BIO-1211 did not show any protection against histamine and acetylcholine-induced bronchoconstriction.

CONCLUSIONBIO-1211 inhibits bronchoconstriction and neutrophil adhesion, which may be associated with its effect against bronchoconstriction in rats.

Administration, Inhalation ; Animals ; Asthma ; drug therapy ; physiopathology ; Bronchoconstriction ; drug effects ; physiology ; Bronchodilator Agents ; administration & dosage ; pharmacology ; Cell Adhesion ; drug effects ; Female ; Guinea Pigs ; Male ; Neutrophils ; cytology ; drug effects ; Oligopeptides ; administration & dosage ; pharmacology ; Rats