BACKGROUNDLactate dehydrogenase (LDH) is a crucial regulator of energy metabolism in many organs including the heart. Lovastatin is widely used in prevention and treatment of coronary heart disease and is a drug with substantial metabolic influences. Our study aimed to determine the activities of the lactate dehydrogenase A and B (LDHA and LDHB) genes following lovastatin treatment.

METHODSThe rat myocardial cell line H9c2(2-1) in culture was exposed to 100 nmol/L lovastatin for 24 hours or for five days. The functions of the LDHA and LDHB genes were examined at the transcriptional (mRNA) level with quantitative real-time polymerase chain reaction (Q-RT-PCR), and at the translational (protein) level with immunoblotting.

RESULTSWhen compared with control levels, the LDHA mRNA went up by (151.65 ± 16.72)% (P = 0.0132) after 24 hours and by (175.28 ± 56.54)% (P = 0.0366) after five days of lovastatin treatment. Although 24 hours of lovastatin treatment had no significant effects on LDHB mRNA levels, when the treatment was extended to five days, LDHB mRNA levels were significantly down-regulated to (63.65 ± 15.21)% of control levels (P = 0.0117). After 24 hours of treatment with lovastatin, there were no significant changes in protein levels of either LDHA or LDHB. When treatment time was extended to five days, the protein levels of LDHA were up-regulated by (148.65 ± 11.81)% (P = 0.00969), while the protein levels of LDHB were down-regulated to (64.91 ± 5.47)% of control levels (P = 0.0192).

CONCLUSIONSLovastatin affects gene activities of LDHA and LDHB differently, which may reveal novel pharmacological effects of lovastatin.

Animals ; Anticholesteremic Agents ; pharmacology ; Blotting, Western ; Cell Line ; Isoenzymes ; genetics ; metabolism ; L-Lactate Dehydrogenase ; genetics ; metabolism ; Lovastatin ; pharmacology ; Myocytes, Cardiac ; drug effects ; enzymology ; Rats ; Reverse Transcriptase Polymerase Chain Reaction

AIMTo synthesize four water-soluble metal porphyrins [5, 10, 15, 20-tetra[4-(4'-pyridine-1) butyloxy phenyl] metalloporphyrins bromide, metal = Zn (I), Cu (II), Mn (III) and Co (IV)] as analogous enzyme having two anti-active oxygen functions.

METHODSThe first function, scavenging O2-, has been proved by using riboflavine-methionine photoreduction methods. The second function, scavenging H2O2, has been demonstrated by using the oxidating Vit C. The third function, scavenging HO*, has been demonstrated by using Fenton reaction. The complexes were measured by the mice liver homogenate technique of mice.

RESULTSFour model compounds could scavenge O2- in the concentration range of 1.0 x 10(-5) - 1.0 x 10(-6) mol x L(-1), decompose H2O2 in the concentration of 1.5 x 10(-6) - 1.0 x 10(-6) mol x L(-1), scavenge HO* in the concentration of 2.0 x 10(-8) - 1.0 x 10(-8) mol x L(-1). All showed that they had obvious action of decreasing the lipid peroxidation in the concentration of 1.0 x 10(-7) mol x L(-1).

CONCLUSIONAll above-mentioned complexes were considered to be qualified analogous enzymes of anti-active oxygen.

Animals ; Cobalt ; Copper ; Free Radical Scavengers ; chemical synthesis ; pharmacology ; Hydrogen Peroxide ; metabolism ; Hydroxyl Radical ; metabolism ; In Vitro Techniques ; Lipid Peroxidation ; drug effects ; Liver ; metabolism ; Malondialdehyde ; metabolism ; Manganese ; Metalloporphyrins ; chemical synthesis ; pharmacology ; Mice ; Reactive Oxygen Species ; metabolism ; Zinc

BACKGROUNDGlucocorticoid signaling exerts major roles in inflammation, metabolism and depression, which are three crucial factors accompanying or underlying coronary heart disease. Although accumulating evidence indicates the influence of glucocorticoids on the pathology and treatment of coronary heart disease, there is still a dearth of pharmaceutical mechanisms for this relationship. This study aimed to investigate the influence of drug treatment on glucocorticoid receptor levels in coronary heart disease.

METHODSEighty hospitalized patients (average age (59.0 +/- 7.5) years, 46 male and 34 female) with coronary heart disease were categorized into four groups with 20 members in each according to one of the four drugs they were treated with. The four drugs were: nitrated derivative isosorbide dinitrate, the beta-adrenergic receptor blocker metoprolol, the calcium antagonist nifedipine, and the HMG-CoA reductase inhibitor lovastatin. Glucocorticoid receptor protein levels of peripheral blood lymphocytes were tested using immunoblotting analysis before and after one month of treatment.

RESULTSImmunoblotting analysis showed increased glucocorticoid receptor levels after treatment with metoprolol and nifedipine. There were no statistically significant changes of glucocorticoid receptor levels after treatment with isosorbide dinitrate or lovastatin, although there were trends of up-regulation of glucocorticoid receptor expression after both treatments.

CONCLUSIONSBoth the beta-blocker and the calcium blocker can increase glucocorticoid receptor levels after chronic administration. This effect suggests a mechanism for their anti-inflammatory and other therapeutic roles for coronary heart disease and comorbid disorders.

Aged ; Blotting, Western ; Coronary Disease ; drug therapy ; metabolism ; Female ; Humans ; Isosorbide Dinitrate ; therapeutic use ; Lovastatin ; therapeutic use ; Male ; Metoprolol ; therapeutic use ; Middle Aged ; Nifedipine ; therapeutic use ; Receptors, Glucocorticoid ; metabolism

AIMTo improve the biological activity of A-ring modified analogues of camptothecin.

METHODSA-ring modified camptothecins were synthesized from 10-hydroxycamptothecin or 7-ethyl-10-hydroxycamptothecin (SN-38) in three or four steps. Their cytotoxicity was evaluated using MTY assay, and their in vivo antitumnor activity against mouse liver cancer H22 was tested. Results Five hexacyclic camptothecins (6a, 6b, 6c, 7a and 7b) are target compounds, and ten camptothecin derivatives are new compounds.

CONCLUSIONThe modification of a 1,4-oxazine-2-one ring fused with positions 9 and 10 of A-ring will reduce the antitumor activity of camptothecins.

Animals ; Antineoplastic Agents ; chemical synthesis ; pharmacology ; Camptothecin ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Carcinoma, Hepatocellular ; drug therapy ; pathology ; Cell Line, Tumor ; drug effects ; Female ; Humans ; Liver Neoplasms ; drug therapy ; pathology ; Mice ; Neoplasm Transplantation ; Polycyclic Compounds ; chemical synthesis ; pharmacology

To explore CD34(+) antigen expression in new diagnosed acute myeloid leukemia (AML) and analyze the prognosis for CD34(+) AML patients, the expression of antigen CD34 in 238 AML patients was detected by indirect immunofluorescence assay. The results showed that CD34 in 92 out of the 238 patients (38.7%) were positive, there was relationship between the CD34(+) expression and FAB subtypes (M(0), M(1)), and no CD34(+) expression was observed in M(3) subtypes. The complete remission rate of CD34(+) AML patients was 32%, which was lower than that of CD34(-) AML (61%). The lymphoid-associated antigen (CD7) was significantly increased in CD34(+) AML patients, compared with CD34(-) patients (P < 0.05). It is concluded that CD34(+) AML patients show poor prognosis and lower CR rate. The detection of CD34 expression is of some value in predicting prognosis in AML.
Adolescent ; Adult ; Aged ; Antigens, CD34 ; biosynthesis ; Antigens, CD7 ; biosynthesis ; Female ; Fluorescent Antibody Technique, Indirect ; Humans ; Leukemia, Monocytic, Acute ; metabolism ; pathology ; Leukemia, Myeloid, Acute ; metabolism ; pathology ; Leukemia, Myelomonocytic, Acute ; metabolism ; pathology ; Male ; Middle Aged ; Prognosis