A New Competitive Inhibitory Monoclonal Antibody to Carboxypcptidase A(CPA)

The monoclonal antibody ID11D7 to carboxypeptidase A (CPA) was prepared. Theinhibitory effect of McAb ID11D7 on the peptidase activity of CPA was measured. The result reflectsthat the McAb ID11D7 can competitively inhibit the peptidase activity of CPA with an apparentinhibitory constant of 6.3 × 10-9M. Based on this work. the McAb ID11D7 can be used as idiotypicantigen to prepare anti-idiotypic catalytic antibody with the peptidase activity similar to CPA.

Ovarian growing teratoma syndrome with multiple metastases in the abdominal cavity and liver:A case report

BACKGROUND Growing teratoma syndrome(GTS)is an unusual presentation of an amazing transformation of teratoma from malignant to benign on pathology during or after systemic or intraperitoneal chemotherapy.The definitive pathogenesis is still not fully understood due to the lack of large-sample studies.CASE SUMMARY A 53-year-old woman underwent radical surgery and postoperative intraperitoneal chemotherapy due to immature teratoma of the right ovary at the age of 28.She remained well during a 25-year follow-up period after surgery.Multiple asymptomatic solid masses were found in the liver on ultrasonography a month ago.Enhanced computed tomography(CT)of the abdomen revealed multiple masses in the abdominal cavity.The largest one was located in the posterior peritoneum next to the sixth segment of the right liver,about 7.9 cm×7.5 cm in size.Three masses were present inside the liver,and one mass was in the right pelvic floor.Multiple lumps in the abdominal cavity were completely removed by surgery.During the operation,multiple space-occupying lesions were seen,ranging in size from 0.5 to 3 cm,and grayish white in color and hard in texture.Ovarian GTS was finally diagnosed based on postoperative pathology.After surgery,she recovered uneventfully.During a 3-year follow-up,the patient remained free of the disease without any recurrence on CT scan.CONCLUSION GTS is a rare phenomenon characterized by conversion of immature teratoma to mature one during or after chemotherapy and presents as growing and metastasizing masses.The pathogenesis of GTS is unclear,and the prognosis is good after surgical resection.

Thermokinetic Study on the Reversible Competitive Inhibition of Bovine Liver Arginase

A new thermokinetic reduced extent method for studying of the reversible competitive inhibition of single sub-strate enzyme-catalyzed reactions was proposed in this paper. The reaction that arginase-catalyzed hydrolysis of L-arginine to L-ornithine and urea and the inhibition of this reaction by the product, L-ornithine, and exogenous L-lysine were studied at 37 ℃ in 40 mmolL-1 sodium barbiturate-HCl buffer solution (pH=9.4). Michealis con-stant Km for arginine and maximum velocity Vm of the reaction were determined to be 5.14 mmolL-1 and 1.13× 10-2 mmolL-1s-1, respectively. The product inhibition constant KP and inhibitory constant KI of L-lysine were de-termined to be 1.18 and 5.6 mmolL-1, respectively. All the results have better repeatability and self-consistency and are in agreement with literature values. This new method using more direct thermal information from the proc-ess would give more reliable kinetic information than the traditional initial rate method.

Organophosphate esters cause thyroid dysfunction via multiple signaling pathways in zebrafish brain

Organophosphate esters(OPEs)are widespread in various environmental media,and can disrupt thyroid endocrine signaling pathways.Mechanisms by which OPEs disrupt thyroid hormone(TH)signal transduction are not fully understood.Here,we present in vivo-in vitro-in silico evidence establishing OPEs as environmental THs competitively entering the brain to inhibit growth of zebrafish via multiple signaling pathways.OPEs can bind to transthyretin(TTR)and thyroxine-binding globulin,thereby affecting the transport of TH in the blood,and to the brain by TTR through the blood-brain barrier.When GH3 cells were exposed to OPEs,cell proliferation was significantly inhibited given that OPEs are competitive inhibitors of TH.Cresyl diphenyl phosphate was shown to be an effective antagonist of TH.Chronic exposure to OPEs significantly inhibited the growth of zebrafish by interfering with thyroperoxidase and thyroglobulin to inhibit TH synthesis.Based on comparisons of modulations of gene expression with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases,signaling pathways related to thyroid endocrine functions,such as receptor-ligand binding and regulation of hormone levels,were identified as being affected by exposure to OPEs.Effects were also associated with the biosynthesis and metabolism of lipids,and neuroactive ligand-receptor interactions.These findings provide a comprehensive understanding of the mechanisms by which OPEs disrupt thyroid pathways in zebrafish.

Efficacy of Silene arenosa extract on acetylcholinesterase in Bungarus sindanus(krait) venom

OBJECTIVE:To examine the efficacy of Silene arenosa extract on acetylcholinesterase (AChE) of krait (Bungarus Sindanus) snake venom.METHODS:The present project designed to evaluate the inhibition of AChE by following standard procedures.RESULTS:Statistical analysis of the results showed that Silene arenosa exerted 73%inhibition against the krait venom acetylcholinesterase at fixed substrate acetylcholine (ACh) concentration (0.5 mM).Kinetic analysis using the Lineweaver Burk plot revealed that Silene arenosa caused a competitive type of inhibition i.e.K_(m) values increased from 26.6 to 93.3 mM (26.6%to 93.3%) and V_(max)remained constant in a concentration-dependent manner.Silene arenosa competes with the substrate to bind at the active site of the enzyme.The K_(mapp)of venom AChE for Silene arenosa increased from 60%to 81.6%and the V_(maxapp)remains constant.K_(i)(inhibition constant was estimated to be 48μg for snake venom);while the K_(m)(Michaelis-Menten constant of AChE-substrate into AChE and product) was estimated to be 0.5 mM.The IC_(50)of AchE calculated for Silene arenosa was 67μg.CONCLUSION:The present results suggest that Silene arenosa extract can be considered as an inhibitor of snake venom AChE.

Nucleotide binding domain 1 pharmacophore modeling for visualization and analysis of P-glycoprotein-flavonoid molecular interactions

BACKGROUND： P-glycoprotein （P-gp） is a 170-kDa membrane protein. It provides a barrier function and help to excrete toxins from the body as a transporter. Some bioflavonoids have been shown to block P-gp activity. OBJECTIVE： To evaluate the important amino acid residues within nucleotide binding domain 1 （NBD l） of P-gp that play a key role in molecular interactions with flavonoids using structure-based pharmacophore model. METHODS： In the molecular docking with NBD 1 models, a putative binding site of flavonoids was proposed and compared with the site for ATP. The binding modes for ligands were achieved using LigandScout to generate the P-gp-flavonoid pharmacophore models. RESULTS： The binding pocket for flavonoids was investigated and found these inhibitors compete with the ATP for binding site in NBD1 including the NBD1 amino acid residues identified by the in silico techniques to be involved in the hydrogen bonding and van der Waals （hydrophobic） interactions with flavonoids. CONCLUSION： These flavonoids occupy with the same binding site of ATP in NBD1 proffering that they may act as an ATP competitive inhibitor.