The study of peptide drugs has been an important direction in research and development of new drugs. However, lots of natural macromolecular peptides are limited in clinical use by their metabolic instability and low bioavailability. In recent years, the active small peptidomimetics open up a new hotspot of peptide drug development with the characteristics of low molecular weight, high bioactivity and structural modification. Many peptidomimetics are on the market or on the clinical study. This paper elaborated the small peptidomimetics approved by American Food and Drug Administration (FDA) from 2005 to 2014, and reviewed their researching status with source, synthetic method, chemical structure, marketing time, indication, clinical efficacy and safety. Research prospects in this field were discussed.
Biomedical Research ; trends ; Peptidomimetics ; United States ; United States Food and Drug Administration

0.05).Conclusions The expression of PBMC IP-10 mRNA increases in KD.IP-10 may participate in the pathogenesis of KD and CAL in KD.Perhaps the inhibition to the expression of PBMC IP-10 mRNA is one of the mechanisms of IVIG.

Objective To investigate the dual pharmacology characteristics of a new structural telmisartan derivative Tek- 1 based on angiotensin II (ANGII) receptor I (AT1) and peroxisome proliferator-activated receptor-γ (PPARγ) and the influence of Tek- 1 on blood pressure in spontaneously hypertensive rats (SHR). Methods The AT1 receptor affinity of Tek- 1 was explored through radioligand binding assay on rat primary vascular smooth muscle cells; the PPARγ agonistic activity of Tek-1 was explored using PPARγ-responsive element-luciferase report assay; the antagonistic effect of Tek-1 on AT1receptor activation induced by ANGII was explored using intracellular calcium mobilization detection assay; the effect of Tek-1 on the regulation of systolic blood pressure (SBP) was evaluated in SHR in vivo. Results Tek-1 and telmisartan had high affinity to AT1 receptor, their Ki values for AT1 receptor were 1.1×10-9 and 2.3×10-10mol/L, respectively. Tek-1 and telmisartan could activate PPARγ ranging from 0.1 to 10 μmol/L in a concentration-dependent manner. The relative lucifarase activity induced by Tek-1 and telmisartan were 1.56±0.08 and 1.39±0.14 fold at 10 μmol/L. Compared with solvent group, the effect of AT1 agonist ANGII were inhibited by Tek-1 in a concentration-dependent manner with IC50 value of 1.02±0.1 nmol/L ranging from 0.0128 to 1 μmol/L. SHR were randomly administered telmisartan (5 or 10 mg/kg) and Tek-1 (1 mg/kg, 5 mg/kg or 10 mg/kg) orally each day for one week every day. After 1-week treatment, compared with the baseline SBP and DBP in the pretreatment of SHR, telmisartan in the dose of 5 and 10 mg/kg both showed significantly decreased SBP (P < 0.01) and DBP (P < 0.05). Tek-1 in the dose of 1, 5 and 10 mg/kg also significantly decreased SBP (P < 0.05); however, only the high dose of 10 mg/kg Tek-1 showed a significant decrease in DBP (P < 0.05). Conclusion Tek-1 Behaveds as an ATI blocker with partial PPARγ agonist activity in vitro and attenuates the blood pressure in SHR in vivo.

Breast Neoplasms ; metabolism ; pathology ; surgery ; Carcinoma, Lobular ; metabolism ; pathology ; secondary ; surgery ; Carrier Proteins ; metabolism ; Female ; Glycolipids ; metabolism ; Glycoproteins ; metabolism ; Humans ; Mastectomy, Modified Radical ; Middle Aged ; Rectal Neoplasms ; secondary

Objective To investigate the proliferation rule after autografl vein in autografl of vein and repairing arterial defect,discuss the minuteness structure changes related to time,and provide morphological date for the prevention and treatment of restenosis in clinic application.Methods Sixty canine femoral veins (3.5 cm and 5.5 cm) were excised,reversed and grafted to repairing femoral arterial defect using end- to-end anastomosis.During the period of 30-180 days excised the grafted veins,observed ultrastrural changes of endothelium,microstructural components relative content and patency in grafted veins through angiography, lipht microscope.Results Angiography show that the grafted vein wall get gradually thicker,vascular cavity get slender,and vessel elasticity shrinkage.Light microscope chalrify the ultrastructural changes of endotheh- um,the three lamine structure of grafted vascular wall could not be identified.Conclusion Grafted femoral veins had obviously arteriosclerosis trend after it was transplanted to the arterial system.Two months after the transplantation is the crisis time of the proliferation of the vascular wall.The effect of the proliferation of the grafted veins vascular wall and the impact of the hi-pressure of blood can lead some canine ruptured to die from pseudoaneurysms.

OBJECTIVETo observe the therapeutic effect of the low molecular weight heparin calcium (LMWHC) combined with Yinxin Damo Injection (YDI) on the prevention of deep venous thrombosis (DVT) after the operation of intertrochanteric fracture.

METHODSSixty-two patients with intertrochanteric fracture were randomly assigned to the control group and the combined group, 31 in each group. Patients in the control group were subcutaneously injected with 6 000 IU LMWHC, twice daily. On this basis of the aforesaid treatment, patients in the combined group were intravenously dripped with YDI at the daily dose of 20 mL, once daily. The treatment lasted for 10 days in both groups. The DVT incidence rate, postoperative drainage amount of blood, activated partial thromboplastin time (APTT), plasma prothrombin time (PT), platelet count, and the maximal swelling rate of lower limbs after surgery were compared between the two groups after operation.

RESULTSIn the control group DVT occurred in 5 cases (16. 1%) while it occurred in 2 cases (6.5%) in the combined group, showing significant differences (P < 0.05). Both APTT and PT were shortened in the two groups on the 2nd day after medication (P < 0.01). Compared with the control group, it was more obvious in the combined group, showing statistical significance (P < 0.05). Both APTT and PT were shortened in the control group on the 10th day after medication when compared with before treatment (P < 0.01). But they were postponed in the combined group when compared with before medication, showing statistical difference when compared with the control group (P < 0.05). The platelet count increased in the combined group on the 10th day after medication. Besides, it was higher than that in the control group, showing statistical difference (P < 0.05). The platelet counts were in the normal range.

CONCLUSIONSLMWSC combined with YDI could not only reduce the incidence of DVT after the operation of intertrochanteric fracture, but also change the state of higher blood coagulation. It showed significant effect on preventing DVT after the operation of intertrochanteric fractures.

Aged ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Ginkgo biloba ; Heparin, Low-Molecular-Weight ; therapeutic use ; Hip Fractures ; surgery ; Humans ; Injections ; Lower Extremity ; blood supply ; Male ; Middle Aged ; Postoperative Complications ; prevention & control ; Venous Thrombosis ; prevention & control

Child, Preschool ; Chondromatosis, Synovial ; diagnosis ; diagnostic imaging ; surgery ; Diagnostic Errors ; Female ; Humans ; Tibial Fractures ; diagnosis ; Tomography, X-Ray Computed

OBJECTIVETo establish the methods for isolation, purification and function identification of Syrian golden hamster islets.

METHODSThe Langerhans islets were isolated and purified from golden hamster pancreas by intra-ductal collagenase V perfusion and discontinuous Ficoll density gradient centrifugation. After isolation, the islet yield and purity were evaluated with DTZ staining. The islet function was assessed using glucose-stimulated insulin secretion test.

RESULTSThe total number of purified islets from one donor hamster was 359-/+35 islet equivalent (IEQ), with the purity and viability of the isolated islets of more than 90%. In response to glucose stimulations at 5.8 and 16.7 mmol/L, the secretion of insulin by the islets was 3.29-/+0.3 and 11.12-/+0.57 mU/L, respectively, showing a 2.28-fold higher insulin release by high-concentration than by low- concentration glucose stimulation (P<0.01).

CONCLUSIONThe methods of collagenase V digestion and gradient centrifugation result in high yield and high purity of the isolated hamster islets.

Animals ; Cell Separation ; methods ; Cricetinae ; Insulin ; secretion ; Islets of Langerhans ; cytology ; Male ; Mesocricetus

In order to establish HPLC fingerprint of Liuwei Dihuang soft capsule, and to provide certain reference for an quality control of it, the HPLC method was performed on an Agilent C18 (4.6 mm x 250 mm, 5 μm) column with acetonitrile-0.02% trifluoroacetic acid as mobile phase, gradient elution volume flow of 1.0 mL x min(-1), column temperature was 30 degrees C, detection wavelength: 0-60 min, 238 nm, 60-70 min, 210 nm. The software for chromatographic fingerprint was applied to analysis different batches of Liuwei Dihuang soft capsule samples. Sixteen mutual peaks were selected as the fingerprint peaks in 12 samples with loganin as the reference peak, and all of the detected peaks were separated effectively. Cluster analysis (HCA) and similarity analysis (SA) were done based on data of 12 samples clustering analysis of 12 batches of samples were divided into 2 categories. Including 7 for the first class, the rest was second, similarities calculated by SA were all above 0.92, indicating a good similarity between the reference and twelve batches of samples, also, the analysis results of HCA and SA basically the same. This method is simple with good precision, repeatability and stability, and provides the basis for Liuwei Dihuang soft capsule quality control.
Capsules ; analysis ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; Quality Control

BACKGROUNDThe Taq/B, Msp/ and I405V polymorphisms of cholesteryl ester transfer protein (CETP), an important regulatory factor of lipid metabolism, have been attracted much more attention by the researchers. In this study, we investigated the associations between these 3 polymorphisms of CETP gene and variations in plasma lipid and lipoprotein levels in patients with coronary heart disease (CHD).

METHODSGenomic DNA was extracted from leukocytes of 203 CHD patients and 100 control subjects using the salting out method. Genotyping of the CETP gene was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. Statistical analysis was conducted using the SPSS 10.0 software package.

RESULTSThe distribution of allele and genotype frequencies of the Taq/B, MspI, and I405V polymorphisms was similar in the CHD patient group and the control group. The B1B1 genotype of the Taq/B polymorphism was associated with significantly higher TC (P=0.039) and LDL-C (P=0.044) levels than the B2B2 genotype in CHD patients, and with significantly higher LDL-C (P=0.034) levels than the B2B2 genotype in controls. Homozygotes of the I405V polymorphism exhibited significantly higher HDL-C levels than VV homozygotes among control subjects (P=0.023). In male CHD patients with unambiguously assigned haplotypes, B2-M2-V/B2-M2-I patients demonstrated significantly higher HDL-C concentrations than B1-M2-V/B1-M2-I (P=0.023) and B1-M2-V/B1-M2-V patients (P=0.047).

CONCLUSIONSGenetic variations in the CETP gene may account for a significant proportion of the differences in plasma lipid and lipoprotein concentrations among the general population. The B1B1 genotype of the Taq/B polymorphism is probably a genetic risk factor for CHD in the study population.

Adult ; Aged ; Carrier Proteins ; genetics ; Cholesterol Ester Transfer Proteins ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Coronary Disease ; blood ; genetics ; Female ; Gene Frequency ; Glycoproteins ; genetics ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Polymorphism, Genetic