To investigate the anticancer effects of ring C in 18β-glycyrrhetinic acid (GA), a series of GA derivatives featured with 9(11)-ene moiety in ring C were designed and synthesized. The structures were confirmed by IR, LC-MS and 1H NMR. Their inhibitory effects towards human prostate cancer PC-3 and leukemia HL-60 cell lines were determined. Most of the derivatives displayed stronger antiproliferative activities than GA. Particularly, compound 14 showed promising anticancer activity with the GI50 values of 4.48 µmol · L(-1) and 1.2 µmol · L(-1) against PC-3 and HL-60 cells respectively, which is worth further study.
Antineoplastic Agents ; chemistry ; pharmacology ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; drug effects ; Drug Design ; Glycyrrhetinic Acid ; analogs & derivatives ; chemistry ; HL-60 Cells ; drug effects ; Humans ; Male ; Prostatic Neoplasms ; pathology

Objective To investigate the protective effect of continuous intravenous infusion of Isoproterenol (ISO)on myocardial mitochondria of early septic rats and the corresponding mechanism.Methods Thirty Sprague Dawley (SD)rats were randomly divided into 5 groups (6 cases per group):control group,endotoxin group,ISO small-dose group,ISO medium-dose group and ISO large-dose group.Endotoxin group and ISO intervene group received same management apart from drug intervention:receiving intravenous injection of lipopolysaccharide (LPS)10 mg/kg followed by an continuous intravenous infusion of 9 g/L saline 1 mL/h or ISO 0.06 μg/(kg · min),0.30 μg/(kg · min)and 0.60 μg/(kg · min).Control group received intraperitoneal injection and continuous intravenous infusion with the same amount of 9 g/L saline.The primary endpoint of the study was 24 hours after injection of 9 g/L saline or LPS.Serum creatine kinase (CK) and creatine kinase isoenzyme (CK-MB),oxidative and nitrosative stress levels and swelling of isolated heart mitochondrion were detected.The pathological changes of the myocardium and morphologic changes of the heart mitochondria were observed through light microscope and scanning electron microscope,respectively.Results The levels of CK,CK-MB,nitric oxide (NO) content,inducible nitric oxide synthase (iNOS) activity and malondialdehyde (MDA)content in endotoxin group were increased compared with control group (all P ＜ 0.05),while the superoxide dismutase (SOD) activity decreased [(11.543 ± 1.080) U/mg prot vs (9.892 ±0.815) U/mg prot,P ＜0.05].The morphology of the heart mitochondria significantly changed (such as swelling,disordered arrangement,crest fracture,fusion and cavitations,and so on).ISO intervention significantly decreased the levels of CK,CK-MB and mitochondrial swelling (all P ＜ 0.05) and increased the SOD activity (all P ＜ 0.05).The levels of NO content,iNOS activity and MDA content were significantly decreased in small-dose group [(10.823 ± 2.240) μmol/g prot vs (7.917 ± 2.203) μmol/g prot,(0.045 ± 0.008) U/mg prot vs (0.033 ± 0.003) U/mg prot,(1.663 ± 0.618) mmol/mg prot vs (0.768 ± 0.312) mmol/mg prot,all P ＜ 0.05],while the levels of iNOS activity and MDA content were significantly increased in medium-and large-dose group (all P ＜ 0.05) ; compared with medium-dose group,the degree of mitochondrial swelling in large-dose group increased (1.160 ± 0.186 vs 1.393 ± 0.128,P ＜ 0.05).The pathological changes of the myocardium mitochondria significantly improved.Conclusions The myocardium and myocardial mitochondria of early septic rats were damaged,continuous intravenous infusion of low-dose ISO revealed protective effect on these damages,and the corresponding mechanism may relate to the decrease of the oxidative and nitrosative stress.

As a new hypnotic, zopiclone is widely used in clinical treatment. There are many methods for determination of zopiclone, including spectrophotometry, chromatography and chromatography mass spectrum, etc. Present paper reviews different kinds of biological samples associated with zopiclone, ex-traction and purification methods, and determination and analysis methods, which aims to provide refer-ences for the relevant research and practice.

OBJECTIVETo explore the inflammatory cascade mechanism through Toll like receptor 2 (TLR2) pathway after cerebral ischemia/reperfusion, and to study molecular mechanisms of Guanmaitong (GMT) Tablet for protecting brain damage.

METHODSWe used bolt-line method to block/release the middle cerebral artery, causing cerebral ischemia/reperfusion (I/R) injury model. GMT Tablet was given by gastrogavage. Rats were then divided into the high dose GMT group (1200 mg/kg), the middle dose GMT group (600 mg/kg), the low dose GMT group (300 mg/kg), the positive control group (Tanakan, 20 mg/kg). Their right brain tissues were fixed in 10% neutral formalin. TLR2 expressions were detected by immunofluorescence staining. The total protein was extracted from right brain tissues by ultrasonica- tion. Expression levels of extracellular regulated protein kinases (ERK), phospho-extracellular regulated protein kinases (p-ERK), p38-mitogen activated protein kinases (p-ERK), phospho-p38-mitogen activated protein kinases [p-p38-MAPKs(p-p38)] were assessed by Western blot. Abdominal aortic blood was withdrawn. IL-6 and IL-1β levels were detected by ELISA in brain tissues and serum.

RESULTSCompared with the sham-oepration group, expression levels of TLR2, ERK, p-ERK, p38, p-p38 protein were up-regulated (P < 0.05, P < 0.01), and contents of IL-6 and IL-1β in brain tissues and serum were increased in the model group (P < 0.01). Expression levels of TLR2, ERK, p-ERK, p38, p-p38 were down-regulated (P < 0.05, P < 0.01), and contents of IL-6 and IL-1β were reduced in brain tissues and serum in middle and high dose GMT groups (P < 0.05, P < 0.01).

CONCLUSIONSTLR2 pathway was involved in cerebral I/R injury. GMT protected neurons by down-regulating protein expressions of TLR2, ERK, p-ERK, p38, p-p38 and contents of IL-1β and IL-6.

Animals ; Blotting, Western ; Brain Ischemia ; metabolism ; Cerebral Infarction ; Down-Regulation ; Drugs, Chinese Herbal ; therapeutic use ; Interleukin-1beta ; Interleukin-6 ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; Tablets ; Toll-Like Receptor 2 ; metabolism ; Up-Regulation ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVEHuman rhinovirus (HRV) is the most common respiratory pathogen, which causes not only acute respiratory infection and community acquired pneumonitis in children, but also asthma episode and deterioration. However, the detection of respiratory pathogen, which mainly focuses on respiratory syncytial virus, influenzaviruses A and B, parainfluenza viruses 1-3 and adenoviruses, does not include HRV yet by now in China. The absence of detection method limits the clinical understanding of HRV pathogenicity, and causes unreasonable use of antibiotics. This study aimed to establish a one-step reverse transcription (RT) PCR system for detecting specific fragment of HRV RNA, and to analyze the sequences of amplicons.

METHODSA pair of degenerate primers based on the HRV highly conserved 5'' noncoding region (NCR) were used to develop a one-step RT-PCR system for detecting HRV RNA in nasopharyngeal aspirates from 78 children with acute respiratory tract infections in the spring of 2004. All the positive PCR products were sequenced, and the sequences of the nucleotides were analyzed by using biological software and compared with those in the GeneBank.

RESULTSEleven (14.1%) of 78 samples were positive on RT-PCR, these patients were clinically diagnozed as upper respiratory tract infection (n = 7), bronchitis (n = 3) and bronchopneumonia (n = 1), respectively. Compared with the sequences of clinical and standard HRV viruses in the GeneBank, the nucleotide sequences of these 11 amplicons shared high homology of 89%-95.5%. Within the 11 amplicons, nucleotide identity varied from 75.2% to 91.8%, and the ratio of genetic variation was from 8.8% to 31.0%, which occurred in highly conserved regions and usually showed single nucleotide mutation in some special locations. These 11 amplicons attribute to the two branches of HRV cladogram, respectively. Most of mutations in highly conservative domain occurred on single ribonucleotide, mainly as transversion (C/G, A/G) and transition (T/C, A/G), some were mutations among 3 bases (A/C/G, A/T/G, A/C/T). And a few mutations involved two nearby ribonucleotide which were also found in highly conservative domain. However, ribonucleotide deletion and insertion were usually found in highly variable domain.

CONCLUSIONThe findings showed that this one-step RT-PCR system was highly specific, rapid and convenient for the detection of HRV RNA in nasopharyngeal secretions of patients with acute respiratory tract infections and that the genome of HRV viruses was highly variable.

Base Sequence ; Child ; Child, Preschool ; Female ; Genes, Viral ; Humans ; Male ; Molecular Sequence Data ; Picornaviridae Infections ; diagnosis ; virology ; RNA, Viral ; analysis ; Respiratory Tract Infections ; virology ; Reverse Transcriptase Polymerase Chain Reaction ; methods ; Rhinovirus ; genetics ; isolation & purification ; Sensitivity and Specificity ; Sequence Analysis, DNA

BACKGROUNDPeritoneal tuberculosis and primary peritoneal carcinoma can both present as an abdominal mass and ascites with elevated serum CA125. The purpose of our study was to evaluate the clinical features of peritoneal tuberculosis, compare them with features of primary peritoneal carcinoma, and establish definitive diagnostic procedures.

METHODSWe conducted a retrospective study in patients with peritoneal tuberculosis from January 1995 to October 2010 at Peking Union Medical College Hospital. During this time, the data of 38 patients with primary peritoneal carcinoma were reviewed.

RESULTSThe median age was 34 years (range, 19 - 80 years). The most common symptoms were abdominal distension (16/30, 53.3%) and an abdominal mass (12/30, 40.0%). The serum CA125 level was elevated in 25 patients (83.3%). The median level of cancer antigen CA125 was 392.5 U/ml (range, 0.6 - 850.0 U/ml). Abdominal ultrasound revealed a pelvic mass in 25 patients and ascites in 20 patients. Diagnostic laparoscopy was performed in 15 patients (50.0%) and exploratory laparotomy was performed in 12 patients (40.0%), and 3 patients (10.0%) who underwent laparoscopy converted to laparotomy because of severe adhesions. The intraoperative findings were adhesions, multiple white tubercles, and ascites. Frozen tissue sections were obtained in 17 patients, and 14 of whom showed chronic granulomatous reactions. Final pathological examinations confirmed the diagnosis.

CONCLUSIONSPeritoneal tuberculosis should be considered as a differential diagnosis, especially for young women with an abdominal mass, ascites, and elevated serum CA125 levels. Laparoscopy is a useful diagnostic method for peritoneal tuberculosis, and intraoperative frozen sections are recommended when the diagnosis is in doubt.

Adult ; Aged ; Aged, 80 and over ; CA-125 Antigen ; blood ; Diagnosis, Differential ; Female ; Humans ; Male ; Middle Aged ; Peritoneal Neoplasms ; blood supply ; diagnosis ; Peritonitis, Tuberculous ; blood ; diagnosis ; Retrospective Studies ; Young Adult

BACKGROUND: Opportunistic infection of Candida albicans (C. albicans) has become a serious problem in immunocompromised patients. The study aimed to explore the mechanism of enterogenous infection of C. albicans in immunocompromised rats under severe acute pancreatitis (SAP). METHODS: Sprague Dawley (SD) rats (n=100) were randomly assigned into 5 groups as the following: blank group, cyclophosphamide+ceftriaxone+SAP group, cyclophosphamide+ceftriaxone group, cyclophosphamide+SAP group, and cyclophosphamide group. The rats were sacrificed at 5 and 10 days, and their jejunum, colon, mesenteric lymph nodes, pancreas, intestinal content, and blood were quickly collected to detect C. albicans. A region of the 25S rRNA gene was chosen and amplified by polymerase chain reaction (PCR) to differentiate C. albicans genotypes. The amplified products were further sequenced and compared to judge their homology. RESULTS: Compared with the Cyclophosphamide group, the combination of immunosuppressants and broad-spectrum antibiotics significantly increased the colonization of C. albicans in intestine in 5 and 10 days. Pure SAP stress did not increase the opportunistic infection of C. albicans. The PCR products of C. albicans isolates all belonged to the genotype A family, and sequence alignment showed that the amplified fragments were homologous. CONCLUSION: The damage of immune system and broad-spectrum antimicrobial agents are important risk factors for opportunistic fungal infection. Intestinal tract is an important source for genotype-A C. albicans to translocate and invade into bloodstream.

OBJECTIVE The purpose of the present study was to investigate the impact of fluvas-tatin formulation on the pharmacokinetics-genetic polymorphis relationship. METHODS We compared the difference between the pharmacokinetics of fluvastatin as an extended-release (ER) 80 mg tablet and an immediate-release(IR)40 mg capsule in terms of drug metabolism enzyme and transporter ge-netic polymorphisms. In this open-label, randomized, two-period, two-treatment, crossover study, ef-fects of BCRP, SLCO1B1, MDR1, CYP2C9, and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed in 24 healthy individuals.Each treatment duration was 7 days with a washout period of 7 days between the crossover.Serum concentration of fluvastatin was evaluated using high-performance liquid chromatography-tandem mass spectrometry. RESULTS The SLCO1B1 T521C genotype had no statistically significant effect on IR 40 mg capsule of fluvastatinafter single or repeated doses.However,for the ER 80 mg tablet,the SLCO1B1 T521C genotype correlated with the AUC0-24of repeat doses (P=0.01). The CYP2C9*3 genotype correlated with the AUC0- 24after the first dose IR 40 mg capsule (P<0.05); however, the difference between CYP2C9*1/*1 and CYP2C9*1/*3 was not statistically significant after repeated doses. CONCLUSION The effect of SLCO1B1 T521C on fluvas-tatin exposure was observed and was more profound in ER and repeated dose administration than in IR and single dose administration.We recommend that formulation should be incorporated into future pharmacogenomics studies and clinical implication guidelines.

OBJECTIVE: To analyze the clinical pathologic characteristics of cervical intraepithelial neoplasia grade III (CINIII ) and to explore optimal surgery for CINIII patients. METHODS: The clinical pathologic characteristics, surgical treatments, prognosis and history of 383 CINIII patients, who hospitalized from August 2005 to December 2010, were reviewed and analyzed. Among the patients, 213 (55.6%) received cold-knife conization surgery and 170 (44.4%) received ordinary electric knife conization surgery. RESULTS: There was no significant statistic difference between cold-knife conization group and ordinary electric-knife conization group on the level of clearance of the pathologic tissues and the cervical cone diameter and cone high. Intraoperative blood loss was (13.1±5.2) mL and (25.5±17.2) mL. Bleeding of electric knife conization group, compared with that of the cold knife conization group, decreased by nearly 50%. The difference between the 2 groups was significant (P<0.01). Pathological examination after conization operation indicated that 350 out of the 383 patients didn't show pathological upgrade while 33 patients showed pathological development, among which 21 were diagnosed with invasive cervical cancer at Ia1 clincal stage, 7 atIa2 clincal stage and 5 atIb1 clincal stage. In 3 cases (14.3%) Ia1 cervical cancer patients, fertility requirements and negative margins with cervical conization were closely followed up, and one patient (4.8%) with positive margin and fertility requirements had re-conecut. The remaining 17 (80.9%) had resected the uterus outside the fascia (or plus attachments) . All the 12 patients with invasive cervical cancer at Ia2 orIb1 clinical stage received radical hysterectomy. No tumor recurrence was observed in the 383 patients. CONCLUSION Treatment optimazation of CINIII patients should be based on clinical pathological diagnosis and individual requirements. Both cervical conization surgery and total hysterectomy have been proved safe and practical for CINIII patients.
Adult ; Aged ; Cervical Intraepithelial Neoplasia ; pathology ; surgery ; Conization ; methods ; Female ; Humans ; Hysterectomy ; Middle Aged ; Neoplasm Grading ; Uterine Cervical Neoplasms ; pathology ; surgery

Pharmacogenomics (PGx) mainly studies the influence of gene polymorphisms and other genetic characteristics on drug metabolism,efficacy and adverse drug reactions,and aims to provide scientific basis for new drug research and development,clinical trials,registration,and indivi-dualized drug therapy.With the vigorous development of the pharmaceutical industry,PGx has been more and more applied not only in the research and development of new drugs but also in drug post-marketed re-evaluation.PGx can greatly shorten the drug development cycle,reduce the cost of new drug research,and help to optimize the clinical application of drug therapy to improve safety and efficacy.This paper reviews on the specific application of PGx in various stages of clinical research and its developmental prospect.