Amiodarone ; therapeutic use ; Anti-Arrhythmia Agents ; classification ; therapeutic use ; Arrhythmias, Cardiac ; drug therapy ; Child ; Clinical Trials as Topic ; Humans ; Hydantoins ; Imidazoles ; therapeutic use ; Imidazolidines ; Phenethylamines ; therapeutic use ; Piperazines ; therapeutic use ; Sulfonamides ; therapeutic use

Due to the complicated pathogenesis of cardiac arrhythmia, the safe and effective therapeutic strategies for cardiac arrhythmia remain an urgent medical problems in the recent years. In this paper, we introduced the research practice of anti-arrhythmic agents targeting on potassium ion channel. The research progress of anti-arrhythmic agents in up-to-date literatures were also reviewed and prospected.
Amiodarone ; analogs & derivatives ; chemistry ; pharmacology ; therapeutic use ; Animals ; Anti-Arrhythmia Agents ; chemistry ; pharmacology ; therapeutic use ; Arrhythmias, Cardiac ; drug therapy ; physiopathology ; Humans ; Hydantoins ; Imidazolidines ; chemistry ; pharmacology ; therapeutic use ; Molecular Structure ; Piperazines ; chemistry ; pharmacology ; therapeutic use ; Potassium Channel Blockers ; pharmacology ; therapeutic use ; Potassium Channels ; drug effects

Androgen deprivation therapy, which is the standard treatment for metastatic prostate cancer, includes nonsteroidal antiandrogenic drugs, such as flutamide, nilutamide and bicalutamide. Of them, bicalutamide rarely induces interstitial pneumonia. We report a case of bicalutamide-induced interstitial pneumonia. A 68-year old male diagnosed with prostate cancer and multiple bone metastases presented with dry cough and low grade fever for 3 days. He had taken bicalutamide (50 mg/day) for 13 months. High resolution computed tomography revealed ground glass opacity in his right upper lung. The laboratory studies showed no eosinophilia in the serum and bronchoalveolar lavage fluid. Despite the use of antimicrobial agents for 2 weeks, the extent of the lung lesions increased to the left upper and right lower lung. He had no environmental exposure, collagen vascular disease and microbiological causes. Under the suspicion of bicalutamide-induced interstitial pneumonia, bicalutamide was stopped and prednisolone (1 mg/kg/day) was initiated. The symptoms and radiologic abnormalities were resolved with residual minimal fibrosis.
Anilides ; Anti-Infective Agents ; Bronchoalveolar Lavage Fluid ; Collagen ; Cough ; Environmental Exposure ; Eosinophilia ; Fever ; Fibrosis ; Flutamide ; Glass ; Humans ; Imidazolidines ; Lung ; Lung Diseases, Interstitial ; Male ; Neoplasm Metastasis ; Nitriles ; Prednisolone ; Prostatic Neoplasms ; Tosyl Compounds ; Vascular Diseases

OBJECTIVETo investigate the long-term effects of imidapril (IMI) on action potential and calcium and potassium currents in rabbit left ventricular hypertrophic myocytes.

METHODSRabbits were randomly divided into three groups: IMI-treated, hypertrophic and sham-operated control groups. Cardiac hypertrophy was induced in hypertrophy group by partial ligation of the abdominal aorta. In the IMI-treated group, the rabbits were administered IMI (1.5 mg x kg(-1) x d(-1)) for 8 weeks after surgery. In the sham-operated control group, the animals underwent an abdominal laparotomy without further procedure. Whole-cell patch clamp technique was used to record ionic currents.

RESULTSMembrane capacitance was larger in hypertrophic cells than in sham-operated cells or IMI-treated cells. Action potential duration was lengthened in hypertrophic cells and was remarkably shortened by IMI. The density of ICa, L was reduced from 12.8 +/- 0.7 pA/pF in the sham-operated cells, to 7.7 +/- 0.8 pA/pF in hypertrophic cells, while it resembled the control cells after IMI treatment (11.9 +/- 1.0 pA/pF). After IMI treatment, the density of I(Ks,tail) was enhanced from 2.5 +/- 0.1 pA/pF in hypertrophic cells to 4.7 +/- 0.6 pA/pF (n = 7, P < 0.01), which was similar to the sham-operated cells. The densities of Ito and IK1 were significantly increased in IMI-treated cells, from 3.8 +/- 0.4 pA/pF and 3.7 +/- 0.5 pA/pF in the hypertrophic cells to 6.4 +/- 0.8 pA/pF and 6.5 +/- 0.3 pA/pF, respectively, but the IKr densities were not different in the three groups.

CONCLUSIONIMI could reverse the increase in membrane capacitance in hypertrophic cells, shorten action potential duration, and increase the densities of ICa, L, IKs, Ito and IK1 in hypertrophic cells.

Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Calcium Channels ; drug effects ; Female ; Hypertrophy, Left Ventricular ; pathology ; Imidazoles ; pharmacology ; Imidazolidines ; Male ; Myocytes, Cardiac ; drug effects ; metabolism ; Potassium Channels ; drug effects ; Rabbits ; Random Allocation

OBJECTIVETo study the effect of aldose reductase (AR) on expression of fibronectin and collagen IV in cultured rat renal mesangial cells (MsC).

METHODSAR expression plasmid vector (pCDNA3-AR) was constructed by restriction endonuclease digestion and ligation procedures. Stable expression of AR in MsC was established by Lipofectin transfection. Western blot and immunofluorescence analyses were performed to verify the transfection efficiency. Expression of fibronectin and collagen IV proteins were analyzed using Western blot.

RESULTSExpression of fibronectin and collagen IV in naive MsC treated with TGF-beta1 was upregulated in comparison to that of the untreated naive MsC (P < 0.01). MsC transfected with pCDNA3-AR showed a remarkable increase of expression of fibronectin and collagen IV (P < 0.01). Aldose reductase inhibitors (Sorbinil and Zopolrestat) significantly inhibited the expression of fibronectin and collagen IV in naive MsC (P < 0.05).

CONCLUSIONSOverexpression or inhibition of AR activity significantly alters the expression of fibronectin and collagen IV proteins in cultured rat MsC, suggesting that AR plays a significant role in the pathogenesis of glomerulosclersis.

Aldehyde Reductase ; antagonists & inhibitors ; genetics ; metabolism ; Animals ; Benzothiazoles ; pharmacology ; Cells, Cultured ; Collagen Type IV ; metabolism ; Fibronectins ; metabolism ; Genetic Vectors ; Imidazolidines ; pharmacology ; Mesangial Cells ; metabolism ; Phthalazines ; pharmacology ; Plasmids ; Rats ; Recombinant Proteins ; genetics ; metabolism ; Transfection ; Transforming Growth Factor beta1 ; pharmacology

AIMTo investigate the effects of imidapril (IMI) on effective refractory period (ERP) and sodium current (I(Na)) of myocytes in ventricular noninfarction zone of healed myocardial infarction (HMI) in rabbit models.

METHODSRabbits with left coronary artery ligation were prepared and IMI (0.625 mg x kg(-1) x d(-1), 8 weeks) was orally administered. The ERP and sodium current were recorded.

RESULTSThe ERP in HMI heart was prolonged. The ERP in IMI group was lower significantly than that of HMI group. The I(Na) density of myocyte in HMI ventricle decreased obviously. V 1/2 of steady state inactivation of I(Na) shifted to hyperpolarization, and time constant (tau) of recovery from inactivation in HMI ventricular myocyte was longer than that of sham ventricular myocyte. I(Na) density in IMI group increased markedly as compared with that of HMI group.

CONCLUSIONIMI was shown to reverse the abnormal prolongation of ERP in rabbit heart with the HMI and increase I(Na) density. It may be the mechanism of IMI preventing against antiarrhythmia in healed myocardical infarction.

Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Calcium Channels ; metabolism ; Female ; Heart Ventricles ; cytology ; Imidazolidines ; pharmacology ; Male ; Myocardial Infarction ; metabolism ; physiopathology ; Myocytes, Cardiac ; metabolism ; Rabbits ; Refractory Period, Electrophysiological ; drug effects

OBJECTIVE: In view of both the economic importance of ethylenebisdithiocarbamate (EBDC) fungicides in the current agricultural practice and the potential health hazards associated with ethylenethiourea (ETU) exposure, this study aimed to develop and validate a high-pressure liquid chromatography (HPLC) method to determine ETU in biological and environmental samples.

METHODS: The samples were pre-treated according to sample types and were analyzed for ETU using a reversed-phase HPLC system (JASCO?) equipped with UV detector set at 230 nm using C18 bonded silica column and a mobile phase of 0.05M ammonium acetate in methanol (95:5).

RESULTS: The method showed a limit of detection of 0.2 ug/L, with a precision of 3.33 to 12.86 %CV and an accuracy of >90% at 1, 10 and 100 ug/L of ETU in all sample types. The calibration curve was linear from 1 to 200 ug/L for blood, air and water samples and 1 to 2000 ug/L for urine.

CONCLUSION: This method showed an acceptable accuracy, precision, sensitivity and specificity and was used subsequently to determine ETU levels in blood, urine, air, soil and water samples among banana plantation workers.

Ethylenethiourea

PURPOSE: The vascular endothelial growth factor (VEGF) expression of podocyte is one of the well-known major factors in development of diabetic nephropathy. In this study, we investigated the effects of aldose reductase inhibitor, fidarestat on diabetic nephropathy, and renal VEGF expression in a type 1 diabetic rat model. MATERIALS AND METHODS: Twenty four Sprague-Dawley male rats which were performed intraperitoneal injection of streptozotocin and normal six rats were divided into four groups including a normal control group, untreated diabetic control group, aldose reductase (AR) inhibitor (fidarestat, 16 mg.kg(-1).day(-1)) treated diabetic group, and angiotensin receptor blocker (losartan, 20 mg.kg(-1).day(-1)) treated diabetic group. We checked body weights and blood glucose levels monthly and measured urine albumin-creatinine ratio (ACR) at 8 and 32 weeks. We extracted the kidney to examine the renal morphology and VEGF expressions. RESULTS: The ACR decreased in fidarestat and losartan treated diabetic rat groups than in untreated diabetic group (24.79 +/- 11.12, 16.11 +/- 9.95, and 84.85 +/- 91.19, p < 0.05). The renal VEGF messenger RNA (mRNA) and protein expression were significantly decreased in the fidarestat and losartan treated diabetic rat groups than in the diabetic control group. CONCLUSION: We suggested that aldose reductase inhibitor may have preventive effect on diabetic nephropathy by reducing renal VEGF overexpression.
Aldehyde Reductase/*antagonists & inhibitors ; Animals ; Antihypertensive Agents/therapeutic use ; Diabetes Mellitus, Experimental/*drug therapy/*metabolism ; Diabetic Nephropathies/prevention & control ; Imidazolidines/*therapeutic use ; Kidney/*drug effects/*metabolism/pathology ; Losartan/therapeutic use ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Angiotensin/*antagonists & inhibitors ; Vascular Endothelial Growth Factor A

AIMTo evaluate the long-term effectiveness, side effects and compliance rates of two types of drugs (luteinizing hormone-releasing hormone [LHRH] agonist and antiandrogen) that were used individually to treat patients with localized prostate cancer (T1-2) at our institution.

METHODSNinety-seven patients who were diagnosed in the period from April 1997 to January 2000 as having clinically localized prostate cancer (T1-2) received either LHRH agonist (leuprolide acetate 7.5 mg/month) monotherapy (group 1, n = 62) or antiandrogen monotherapy (group 2, n = 35; 18 received bicalutamide 50 mg q.d., 13 received nilutamide 150 mg t.i.d. and 4 received flutamide 250 mg t.i.d.). The mean age in both groups was 76 years.

RESULTSThe mean follow-up time was (50.8 +/- 8.5) months in group 1 and (43.1 +/- 2.2) months in group 2. Prostate-specific antigen (PSA) levels rose in only 1 of the 62 patients (1.6%) in group 1, and in 20 of the 35 patients (57.1%) in group 2. In group 2, 10 of the 20 patients (50%) with increasing PSA levels were treated with LHRH salvage therapy, and eight (80%) responded. Hot flashes (54.8%) and lethargy (41.9%) were the most common side effects in group 1. In contrast, nipple-tenderness (40%) and light-dark adaptation (17.1%) were more often seen in group 2. Only 1 of the 62 patients (1.6%) in group 1 switched to another medication because of adverse side effects; whereas 8 of the 35 patients (22.9%) in group 2 did so.

CONCLUSIONUnlike antiandrogen monotherapy, LHRH agonist monotherapy provided long-term durable control of localized prostate cancer (T1-2). It can also be an effective treatment option for patients whose disease failed to respond to antiandrogen monotherapy. The limitations of our study are the lack of health outcomes analysis and a small sample size.

Aged ; Aged, 80 and over ; Androgen Antagonists ; adverse effects ; therapeutic use ; Anilides ; adverse effects ; therapeutic use ; Flutamide ; adverse effects ; therapeutic use ; Gonadotropin-Releasing Hormone ; agonists ; Humans ; Imidazolidines ; adverse effects ; therapeutic use ; Leuprolide ; adverse effects ; therapeutic use ; Male ; Nitriles ; adverse effects ; therapeutic use ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; drug therapy ; Retrospective Studies ; Tosyl Compounds ; adverse effects ; therapeutic use

OBJECTIVETo study the effects of aldose reductase (AR) on the proliferation of rat mesangial cells (MsC) in vitro and to investigate its mechanism.

METHODSCell proliferation was assessed by MTT colorimetric assay. Cell cycle and apoptosis were analyzed by flow cytometry. The growth of normal MsC and AR transfected MsC was compared. The proliferation of PDGF-BB and cellular growth stimulation by 10% NBS were investigated using AR inhibitors (ARI) Sorbinil and Zopolrestat. The effects of PDGF-BB on the expression of AR, p65 and c-Jun were assessed by Western blot. Activation of AP-1 was measured by EMSA.

RESULTSAR expression of transfected MsC was distinctly higher than that of the control. Transfected MsC grew quicker than normal cells. ARI partially inhibited the proliferation of transfected MsC under the stimulation of PDGF-BB and 10% NBS, whereas 10% NBS had no effect on normal MsC. PDGF-BB upregulated the expression of AR and c-Jun, but had no effect on p65. The upregulation of c-Jun and the activation of AP-1 could be attenuated by ARI.

CONCLUSIONAR may participate in the pathological proliferation of MsC through the pathway related to the activation of AP-1.

Aldehyde Reductase ; antagonists & inhibitors ; genetics ; metabolism ; Animals ; Benzothiazoles ; pharmacology ; Cell Cycle ; Cell Proliferation ; Cells, Cultured ; Genetic Vectors ; Imidazolidines ; pharmacology ; Mesangial Cells ; cytology ; metabolism ; Phthalazines ; pharmacology ; Platelet-Derived Growth Factor ; pharmacology ; Proto-Oncogene Proteins c-jun ; metabolism ; Proto-Oncogene Proteins c-sis ; Rats ; Transcription Factor AP-1 ; metabolism ; Transfection