Statins, a class of cholesterol-lowering drugs, have created a revolution in the prevention and treatment of cardiovascular disease. Mevastatin as the first statin originated from microbial metabolites. Its discovery is connected with the research of the biosynthesis of cholesterol. Atorvastatin, another statin, is one of the most famous blockbuster drugs in the pharmaceuticals market. The legend of statins is not only a success story in science, but also a classical case for business. In this paper, we review the research and development of statins and hope to give some enlightenment to scientists engaged in relevant research.

Objective: To study the biotransformation of gracillin by Penicillium lilacinumACC 31890,to isolate and to identify the structures of metabolites and investigate the pharmacological activities.Methods: The conversion products were isolated and purified by silica gel column chromatography and semi-preparative reversed phase liquid chromatography.Their structures were identified by MS and NMR, and the anti-inflammatory activity of the conversion products was investigated as well.Results: Three metabolites were isolated and purified, and identified as 5R-spirost-5-ene-3-ol-O-β-D-Glucopyranoside-(1→3)-β-D-glucopyranosyl (1), trillin (2) and diosgenin (3) with the conversion rate of 1%, 1% and 45%, respectively.In vitro study showed that the three products showed certain degrees of activity to inhibit the production of NO, IL-6 and MCP-1 in LPS-primed RAW264.7 macrophages.Moreover, the anti-inflammatory activity of the bioconversion products increased along with the hydrolyzation of carbohydrate chain.Diosgenin, the final product, showed the strongest anti-inflammatory activity among the three products.Conclusion: The biotransformation of gracillin by Penicillium lilacinum has a high productivity of diosgenin.The amount of glycosyls has notable influence on the anti-inflammatory activity of steroid sapoinin.

The objectives of this study are to prepare resveratrol loaded mixed micelles composed of poloxamer 403 and poloxamer 407, and optimize the formulation in order to achieve higher drug solubility and sustained drug release. Firstly, a thin-film hydration method was utilized to prepare the micelles. By using drug-loading, encapsulation yield and particle size of the micelles as criteria, influence of three variables, namely poloxamer 407 mass fraction, amount of water and feeding of resveratrol, on the quality of the micelles was optimized with a central composite design method. Steady fluorescence measurement was carried out to evaluate the critical micelle concentration of the carriers. Micelle stability upon dilution with simulated gastric fluid and simulated intestinal fluid was investigated. The in vitro release of resveratrol from the mixed micelles was monitored by dialysis method. It was observed that the particle size of the optimized micelle formulation was 24 nm, with drug-loading 11.78%, and encapsulation yield 82.51%. The mixed micelles increased the solubility of resveratrol for about 197 times. Moreover, the mixed micelles had a low critical micelle concentration of 0.05 mg · mL(-1) in water and no apparent changes in particle size and drug content were observed upon micelles dilution, indicating improved kinetic stability. Resveratrol was released from the micelles in a controlled manner for over 20 h, and the release process can be well described by Higuchi equation. Therefore, resveratrol-loaded poloxamer 403/407 mixed micelles could improve the solubility of resveratrol significantly and sustained drug release behavior can be achieved.
Drug Carriers ; chemistry ; Fluorescence ; Kinetics ; Micelles ; Particle Size ; Poloxamer ; chemistry ; Solubility ; Stilbenes ; chemistry ; Water

Objective To investigate the diagnostic values of imaging techniques and endoscopy in detection the causes of post-hepatic obstructive jaundice.Methods The clinical data of 57 patients with post-hepatic obstructive jaundice were retrospectively studied.The causes of the obstruction and the findings of uhrasonography(US),computerized tomography(CT),magnetic resonance imaging(MRI)or MRIcholangiopancreatography(MRCP),endoscopic retrograde cholangiopancreatography(ERCP)and endoscopic ultrasonography(EUS)were compared.Results The causes of 57 patients with post-hepatic obstruetive jaundice were benign obstruction in 42(including stones in common bile duct in 38,ascariasis of CBD in 1,postoperative stricture in 2 and chronic pancreatitis in 1),and malignant lesions in 15(including pancreatic head carcinoma in 11 and ampullary carcinoma in 4).The diagnostic accuracy in terms of lesion location of US,CT,MRI+MRCP,ERCP and EUS were 71.93%(41/57),88.00%(22/25),94.59% (35/37),100.00%(47/47)and 96.77%(30/31),respectively;the diagnostic accuracy of cause of obstruction were 63.16%(36/57),80.00%(20/25),83.78%(31/37),100%(47/47)and 96.77% (30/31),respectively.Conclusion Benign diseases are the main causes of post-hepatic obstructive jaundice,but malignant ones are not rare.It is important to combine miscellaneous imaging techniques and endoscopy in diagnosis.

In order to clarify the chemical constituents of Si-Wu Decoction rapidly and holistically, we analyzed the ethanol extract of Si-Wu Decoction by UPLC/Q-TOF-MSE and UNIFI which based on traditional Chinese medicine database, the probable structures of 113 compounds were identified. The results show that this method can rapidly and effectively characterize the chemical compounds of Si-Wu Decoction and provide a new solution for identification of components from complex TCM extract.

Objective To evaluate the use of gated SPECT in patients with hypertrophic obstructive cardiomyopathy (HOCM) and the effects of percutaneous transluminal septal myocardial ablation (PTSMA) on myocardial perfusion.Methods 99 Tcm-methoxyisobutylisonitrile (MIBI) and 18F-fluorodeoxyglucose (FDG) images were performed in 31 HOCM patients before PFSMA and in 15 patients 3-7 d after PTSMA.The images in different left ventricular segments were analysed by using scores.Results In 99Tcm-MIBI images, uptake decreased at the septal regions in 12 HOCM patients (80.0%, 12/15) after PTSMA, 18F-FDG images also showed decreased uptake at the septal regions in 5 HOCM patients (33.3%, 5/15) after PTSMA.Conclusion 99Tcm-MIBI images might be an important method to evaluate PTSMA results, and 18 F-FDG images showed important value as reference.

OBJECTIVETo search for an ideal method to repair large facial defects.

METHODSOne or two soft tissue expanders were implanted at the clavicular-pectoral region. After fully expansion, a clavicular-pectoral skin flap was designed and created with similar color, texture, and size to the facial defect. The flap would pass over the neck and transfer to the face to repair a large defect.

RESULTS10 cases were treated with this method. All have been followed up for 12-18 months with satisfactory results.

CONCLUSIONThe large facial defects could be repaired by the expanded clavicular-pectoral skin flap without damaging the natural neck contour and donor site abnormality was avoided. The patients get an aesthetic look and good function.

Adolescent ; Adult ; Child ; Clavicle ; Face ; abnormalities ; surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Pectoralis Muscles ; transplantation ; Reconstructive Surgical Procedures ; methods ; Skin Transplantation ; methods ; Surgical Flaps ; Treatment Outcome

In order to clarify the chemical constituents of Si-Wu Decoction rapidly and holistically, we analyzed the ethanol extract of Si-Wu Decoction by UPLC/Q-TOF-MSE and UNIFI which based on traditional Chinese medicine database, the probable structures of 113 compounds were identified. The results show that this method can rapidly and effectively characterize the chemical compounds of Si-Wu Decoction and provide a new solution for identification of components from complex TCM extract.
Chromatography, High Pressure Liquid ; Databases, Pharmaceutical ; Drugs, Chinese Herbal ; chemistry ; Medicine, Chinese Traditional

Betulinic acid is a naturally occurring pentacyclic triterpenoid, which has antiretroviral, antimalarial, and anti-inflammatory properties. The purpose of this study is to investigate the HBV DNA replication inhibition in the mouse model with betulinic acid. Hydrodynamic injection method via the tail vein with the Paywl. 3 plasmid was used to establish the animal mode (n = 15), and the mice were randomly divided into the PBS control group (n = 5), Betulinic acid treatment group (n = 5) and lamivudine control group (n = 5). The day after successful modeling , the mice would have taken Betulinic acid (100 mg x kg(-1)), lamivudine (50 mg x kg(-1)), PBS drugs orally, once daily for 7 days, blood samples were acquired from the orbital venous blood at 3, 5, 7 days after the administering, HBsAg and HBeAg in serum concentration were measured by ELISA and the mice were sacrificed after 7 days, HBV DNA southern detections were used with part of mice livers. The results showed that betulinic acid significantly inhibited the expression of HbsAg in the mice model at the fifth day compared with the control group, and there was no significant differences between the effects of lamivudine and the PBS control group; both the betulinic acid and lamivudine groups had no significant inhibition for the HBeAg expression; the HBV DNA expressions of the liver tissue from the betulinic acid and lamivudine groups were inhibited compared with the control group. Taken together, these results reveal betulinic acid can inhibit the HBsAg expression and replication of the liver HBV DNA in the mouse model.
Acute Disease ; Animals ; Antiviral Agents ; pharmacology ; DNA Replication ; drug effects ; DNA, Viral ; biosynthesis ; Hepatitis B ; blood ; virology ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; drug effects ; genetics ; immunology ; physiology ; Male ; Mice ; Plasmids ; genetics ; Triterpenes ; pharmacology ; Virus Replication ; drug effects

BACKGROUNDBecause of the pivotal role of the human leukocyte antigen (HLA) class II molecules in regulating the immune response and their extensive polymorphism, it is not surprising that particular HLA class II alleles have been implicated in susceptibility to allergic diseases and in restriction of the IgE responses to a variety of allergens. We investigated the relationship between HLA-DRB genotype and allergies to various penicillins and explored HLA-DRB restriction of IgE responses to these derivatives of penicillin.

METHODSRadioallergosorbent test was used to examine 8 kinds of specific IgE antibodies (4 major and 4 minor antigenic determinants) in the sera of 248 patients with an allergy to penicillins and 101 healthy subjects without any allergic reaction. Some (113 patients and 87 healthy control subjects) were chosen from all subjects to type for HLA-DRB alleles by sequence specific primer-polymerase chain reaction.

RESULTSCompared with control subjects, a significantly increased frequency of DR9 was present in 77 patients with allergic reactions, with immediate hypersensitive reaction and with urticaria (P = 0.011; P = 0.019; P = 0.005 respectively). Conversely, a significantly decreased frequency of DR14.1 was found in 80 patients with positive IgE antibodies, with immediate reaction and with urticaria compared with control group (P = 0.024; P = 0.038; P = 0.038). A possible excess of HLA-DR17 was found in subjects who were responsive to benzylpenicilloyl compared with those were not (chi(2) = 5.134, P = 0.023), and of HLA-DR4 was found in subjects responsive to phenoxomethylpenicillanyl (PVA, chi(2) = 4.057, P = 0.044).

CONCLUSIONHLA-DRB gene may be involved in allergy to penicillins through modulating specific serum IgE to penicillins.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Child ; Child, Preschool ; Drug Hypersensitivity ; genetics ; immunology ; Female ; Genotype ; HLA-DR Antigens ; genetics ; Humans ; Immunoglobulin E ; blood ; Male ; Middle Aged ; Penicillins ; adverse effects ; immunology