Natural phytoestrogens such as the isoflavones genistein and daidzein, and the flavones quercetin exhibit anti-cancer properties. This study was purpose to investigate the anti-proliferative effect of phytoestrogens on acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) cells, and their synergistic antileukemic effect in combination with chemotherapeutic drugs. Optimal dosage of genistein, quercetin and in combination with chemicals for leukemia cells were determined by experiments. Cell viability, apoptosis induction and cell cycle arrest were detected by trypan blue staining, MTT assay, optical microscopy, flow cytometry (FCM). The schedule treatment of combination of genistein and chemicals was determined. The results showed that genistein exhibited a dose- and time-dependent inhibitory effect on cell proliferation in NB4 and HL-60 cells, induced apoptosis and cell cycle arrest in G2/M phase. Quercetin had evident inhibitory effect on the proliferation of K562 and K562/A cells. The combination of genistein and chemicals exerted a synergistic effect on cell growth inhibition. In conclusion, this study demonstrated the synergistic antileukemic effect of genistein with chemotherapeutic drugs on leukemic cells. This combination appears to be a new idea for the clinical novel treatment of leukemia.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Drug Synergism ; Genistein ; pharmacology ; HL-60 Cells ; Humans ; Isoflavones ; pharmacology ; Leukemia, Monocytic, Acute ; pathology ; Leukemia, Myeloid, Acute ; pathology ; Phytoestrogens ; pharmacology ; Quercetin ; pharmacology

This review discusses recent progress in the development of anti-HIV agents, with emphasis on small molecule HIV-1 entry inhibitors. The entry inhibitors primarily target HIV-1 envelope glycoproteins or the cellular receptors, CD4 and chemokine receptors. Two of the entry inhibitors, enfuvirtide and maraviroc, have been approved by the US FDA for AIDS therapy. The drug resistance associated with some of the entry inhibitors will also be discussed.
Anti-HIV Agents ; chemistry ; pharmacology ; therapeutic use ; CCR5 Receptor Antagonists ; CD4 Antigens ; drug effects ; Cyclohexanes ; pharmacology ; therapeutic use ; Drug Resistance, Viral ; HIV Envelope Protein gp120 ; pharmacology ; HIV Envelope Protein gp41 ; pharmacology ; therapeutic use ; HIV Fusion Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV Infections ; drug therapy ; HIV-1 ; drug effects ; Humans ; Molecular Structure ; Peptide Fragments ; pharmacology ; therapeutic use ; Receptors, CCR5 ; physiology ; Receptors, CXCR4 ; antagonists & inhibitors ; Receptors, Chemokine ; drug effects ; Triazoles ; pharmacology ; therapeutic use

INTRODUCTIONCardiopulmonary resuscitation (CPR) guidelines were revised in 2005 based on new evidence and expert consensus. However, the benefits of the new guidelines remain undetermined and their influence has not been published in Asia. This study aimed to evaluate the impact of implementing the new resuscitation guidelines and identify factors that influence the discharge survival of out-of-hospital cardiac arrest (OHCA) patients in an Asian metropolitan city.

MATERIALS AND METHODSThis was an observational cohort study of all OHCA patients seen by the emergency medical service during the period before (Nov 2003 to Oct 2005) and after (May 2006 to Oct 2008) implementing the new resuscitation guidelines. Detailed clinical information was recorded using the Ustein style template. Statistical analysis was done using X2 test or t-test for univariate analysis and the logistic regression model for multivariate analysis.

RESULTSThere were 463 patients before and 430 patients after the new guidelines who received resuscitation. The rate of recovery of spontaneous circulation (ROSC), survival-to-intensive care unit (ICU) admission, and survival-to-hospital discharge all showed no benefits regarding the new resuscitation guidelines (ROSC: 42% vs 39%, P = 0.32; Survival-to-ICU admission: 33% vs 30%, P = 0.27; survival-to-hospital discharge: 10% vs 7%, P = 0.09). The rate of ventricular fibrillation/pulseless ventricular tachycardia (VF/pulseless VT), rate of witnessed arrest, and rate of bystander CPR were much lower than in Western studies. After multivariate logistic regression, factors related to discharge survival were witnessed arrest and initial rhythm with VF/pulseless VT. The new resuscitation guidelines did not significantly influence the discharge survival.

CONCLUSIONSWe did not observe any improvement in survival after implementing the new guidelines. Independent factors of survival-to-hospital discharge are witnessed arrest and initial rhythm with VF/pulseless VT. Because the rates of VF/pulseless VT and bystander CPR in Asia are low, popularising CPR training programmes and increasing the rate of bystander CPR may be more important for improving OHCA survival rates than frequent guideline changes.

Aged ; Aged, 80 and over ; Cardiopulmonary Resuscitation ; methods ; standards ; Emergency Service, Hospital ; statistics & numerical data ; Female ; Hospitals, University ; statistics & numerical data ; Humans ; Male ; Middle Aged ; Out-of-Hospital Cardiac Arrest ; mortality ; therapy ; Patient Discharge ; statistics & numerical data ; Practice Guidelines as Topic ; Survival Analysis ; Taiwan ; epidemiology

Gut functions, such as gastrointestinal motility, gastric secretion and pancreatic secretion, were reduced with age. Glucose tolerance is impaired, and the release of insulin and beta-cell's sensitivity on glucose are reduced with age. However, a lot of controversial data have been reported as insulin concentrations after glucose ingestion are either higher or no different in elderly and young subjects. Thus, this study was aimed to investigate whether aging could affect pancreatic exocrine secretion and its action mechanisms. An isolated perfused rat pancreatic model was used to exclude the effects of external nerves or hormones. Pancreatic secretion was increased by CCK under 5.6 mM glucose background in the isolated perfused pancreas of young (3 months), 12 months and 18 months aged rats. There was no significant difference between young and aged rats. In 3 months old rats, CCK-stimulated pancreatic secretion was potentiated under 18 mM glucose background. However, the potentiation effects of endogenous insulin and CCK were not observed in 12 and 18 months old rats. Exogenous insulin also potentiated CCK-stimulated pancreatic secretion in 3 months old rats. Similarly, exogenous insulin failed to potentiate CCK-stimulated pancreatic secretion as that of 3 months old rats. Wet weight of pancreas and amylase content in pancreatic tissue were not changed with age. These results indicate that pancreatic exocrine secretion is reduced with age and endogenous insulin secretion and/or action is involved in this phenomenon.
Aged ; Aging ; Amylases ; Animals ; Cholecystokinin ; Eating ; Gastrointestinal Motility ; Glucose ; Humans ; Insulin ; Pancreas ; Rats

HIV-1 trans-activator of transcription (Tat) plays a critical role in HIV-1 transcription. Based on the beta-turn motif present in HIV-1 Tat, a series of novel benzodiazepine analogs were designed as beta-turn mimetics and prepared from p-chloro-nitrobenzene/2-phenylacetonitrile, p-toluidine/benzoyl chloride, or (Z)-7-nitro-5-phenyl-1H-benzo[e][1, 4]diazepin-2(3H)-one (nitrazepam) through different synthetic routes. Preliminary biological evaluation indicated that compound 30 exhibited inhibitory activity on HIV-1 tat-mediated LTR transcription with EC50 of 25.0 micromol x L(-1) and showed no obvious cytotoxic effects on TZM-BI cells under the concentration of 100 micromol x L(-1).
Benzodiazepinones ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; HIV Long Terminal Repeat ; genetics ; HIV-1 ; genetics ; Humans ; Transcription, Genetic ; drug effects ; tat Gene Products, Human Immunodeficiency Virus ; antagonists & inhibitors