Cerivastatin inhibits fetal calf serunvinduced DNA synthesis in cultured rat mesangial cells

SUMMARY: Inhibition of mevalonate synthesis by several statins has been shown to suppress DNA synthesis in glomerular mesangial cells. In the present study, we investigated the effect of a new statin, cerivastatin, on fetal calf serum (FCS)-induced DNA synthesis of cultured rat mesangial cells. Cultured rat mesangial cells were stimulated by 10% FCS in the presence or absence of cerivastatin and mevalonate. 5-bromo-2-deoxyuridine (BrdU) incorporation was used to assess DNA synthesis. the present study showed that 10% FCS caused marked stimulation of DNA synthesis in the mesangial cells. Cerivastatin inhibited FCS-stimulated BrdU incorporation in a dose-dependent manner. IC₅₀ was approximately 1 umol/L. Exogenous mevalonate, farnesyl pyrophosphate and geranylgeranyl pyrophosphate significantly prevented the inhibitory effect of cerivastatin on DNA replication. It appears that cerivastatin, by inhibiting the synthesis of mevalonate, may suppress DNA synthesis in the mesangial cells.     

Genetic susceptibility to type 2 diabetic nephropathy in human and animal models

SUMMARY:   Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) in Japan, Western Europe, and the United States. Mega studies such as Diabetes Control and Complication Trial (DCCT), Epidemiology of Diabetes Interventions and Complications (EDIC), and the United Kingdom Prospective Diabetes Study (UKPDS) clarified that poor glycemic and blood pressure control are undoubtedly involved in the development of nephropathy. However, these factors are not sufficient to predict which diabetic patients will develop renal disease, because not all patients with poor glycemic and blood pressure control develop renal disease. Since ethnic variations and familial clustering of diabetic nephropathy have been observed, genetic factors might contribute to susceptibility to this disease. Several methods such as (genome wide) association studies, sib-pair analysis, and quantitative trait loci (QTLs) analysis are available to examine polygenic diseases. However, no mutations that could explain the majority of nephropathy cases have been identified so far. The development of most diabetic nephropathy might be explained by the polygenic effect (i.e. many minor gene-gene interactions might be very important in the development of nephropathy). Identification of candidate genes of nephropathy enables targeting of therapy in patients at risk and development of novel therapeutic agents.     

Pharmacokinetic Analysis of Increased Toxicity of 2-sec-Butylphenyl Methylcarbamate (BPMC) by Fenitrothion Pretreatment in Mice

Pharmacokinetk Analysis of Increased Toxicity of 2-sec-ButylphenylMethylcarbamate (BPMC) by Fenitrothion Pretreatment in Mice.TSUDA, S., MIYAOKA, T., IWASAKI, M., AND SHIRASU, Y. (1984).Fundam. Appl. Toxicol. 4, 724–730. The potentiating effectof O,O-dimethyl O-(3-methyl-4-nitrophenyl) phosphorothioate(fenitrothion) on the toxicity of 2-sec-butylphenyl methylcarbamate(BPMC) in male mice was analyzed pharmacokinetically. The animalspretreated by dietary administration of 1000 ppm fenitrothionfor 1 week (4.4% of the po LD50 daily) did not show toxic symptomsexcept for a slight decrease in body weight In the fenitrothion-pretreatedmice, toxicity of fenitrothion was not changed but a fivefoldpotentiation was observed in po and ip acute lethality and athreefold potentiation of iv lethality of BPMC. Toxic signsafter BPMC administration were similar regardless of fenitrothionpretreatment or of route of administration. Fenitrothion pretreatmentfollowed by BPMC administration (20 mg/kg po or 8 mg/kg iv,approximate LD5 in the pretreated mice) significantly increasedthe plasma BPMC concentration and the total area under the plasmaconcentration versus time curve (AUG_0-. The pretreatment increasedthe oral AUC_0-, more greatly than the iv AUC_0-, (for po, 6.3-fold;for iv, 2.0-fold). The oral systemic availability of BPMC (fractionreaching systemic circulation) was increased by fenitrothiontreatment to 3.3-fold. These results suggest that a major causeof the potentiation may be the increase in amount of BPMC inthe systemic circulation.     

Differences in the Mode of Lethality Produced through Intravenous and Oral Administration of Organophosphorus Insecticides in Rats

Differences in the Mode of Lethality Produced through Intravenousand Oral Administration of Organophosphorus Insecticides inRats. TAKAHASHI, H., KOJIMA, T., IKEDA, T., TSUDA, S. and SHIRASU,Y. (1991). Fundam. Appl. Toxicol. 16, 459–468. This studywas undertaken to investigate the possibility that mechanismsother than cholinesterase (ChE) inhibition account for the acutetoxicity of organophosphorus insecticide. Both the PO type insecticide(direct ChE inhibitors: chlorfenvinphos and dichlorvos) andthe PS type insecticide (indirect ChE inhibitors: diazinon andfenthion) were employed. Rats treated with lethal doses of intravenousand oral PO type insecticides and oral PS type insecticidesexhibited typical signs of anti-ChE poisoning along with markedinhibition of brain and erythrocyte ChE activity. In contrast,rats given lethal doses of intravenous PS type insecticidesexhibited tonic convulsions and opisthotonos, with only slightinhibition of ChE activities. When PO type insecticides wereintravenously administered to anesthetized and conscious rats,animals exhibited typical anti-ChE poisoning signs in cardiorespiration:hypertension and apnea which were antagonized by atropine. Afteradministration of lethal doses of PO type insecticides, breathingdisappeared before the cessation of heart beats. Rats receivinglethal doses of intravenous PS type insecticides did not showhypertension, but exhibited transient cessation of breathingand heart beats. Breathing was observed after the disappearanceof heart beats. The electroencephalogram (EEG) was characterizedby spike and wave complexes. The EEG and cardiorespiratory changeswere not antagonized by atropine. It was concluded that lethalityfollowing intravenous PS type insecticides may be independentof ChE inhibition.     

Cholestatic hepatocellular carcinoma diagnosed by deposits of Lipiodol and treated by combination of endoscopic retrograde biliary drainage and transcatheter arterial embolization

Cholestatic hepatocellular carcinoma, which grows into the bile duct and causes obstructive jaundice, is rare and difficult to diagnose. A case is presented in which cholestatic hepatocellular carcinoma was detected by deposit of Lipiodol. This is also the first case that was successfully treated by endoscopic retrograde biliary drainage and transcatheter arterial embolization.     

Integration of Merged Delayed‐Enhanced Magnetic Resonance Imaging and Multidetector Computed Tomography for the Guidance of Ventricular Tachycardia Ablation: A Pilot Study

MDCT/MRI Fusion for the Guidance of VT Ablation . Background: Delayed enhancement (DE) MRI can assess the fibrotic substrate of scar‐related VT. MDCT has the advantage of inframillimetric spatial resolution and better 3D reconstructions. We sought to evaluate the feasibility and usefulness of integrating merged MDCT/MRI data in 3D‐mapping systems for structure–function assessment and multimodal guidance of VT mapping and ablation. Methods: Nine patients, including 3 ischemic cardiomyopathy (ICM), 3 nonischemic cardiomyopathy (NICM), 2 myocarditis, and 1 redo procedure for idiopathic VT, underwent MRI and MDCT before VT ablation. Merged MRI/MDCT data were integrated in 3D‐mapping systems and registered to high‐density endocardial and epicardial maps. Low‐voltage areas (<1.5 mV) and local abnormal ventricular activities (LAVA) during sinus rhythm were correlated to DE at MRI, and wall‐thinning (WT) at MDCT. Results: Endocardium and epicardium were mapped with 391 ± 388 and 1098 ± 734 points per map, respectively. Registration of MDCT allowed visualization of coronary arteries during epicardial mapping/ablation. In the idiopathic patient, integration of MRI data identified previously ablated regions. In ICM patients, both DE at MRI and WT at MDCT matched areas of low voltage (overlap 94 ± 6% and 79 ± 5%, respectively). In NICM patients, wall‐thinning areas matched areas of low voltage (overlap 63 ± 21%). In patients with myocarditis, subepicardial DE matched areas of epicardial low voltage (overlap 92 ± 12%). A total number of 266 LAVA sites were found in 7/9 patients. All LAVA sites were associated to structural substrate at imaging (90% inside, 100% within 18 mm). Conclusion: The integration of merged MDCT and DEMRI data is feasible and allows combining substrate assessment with high‐spatial resolution to better define structure–function relationship in scar‐related VT. (J Cardiovasc Electrophysiol, Vol. 24, pp. 419‐426, April 2013)     

中日产川芎的matK、ITS基因序列及其物种间的亲缘关系

目的分析中国产川芎Ligusticum chuanxiong Hort.及日本产川芎Cnidium officinale Makino的核基因组ITS和叶绿体基因组matK序列,为探讨中日产川芎物种间的亲缘关系提供分子依据。方法采用PCR直接测序技术测定川芎和日本川芎的ITS基因和matK基因核苷酸序列并作序列变异分析。结果川芎和日本川芎的matK序列长度均为1268 bp,编码422个氨基酸。ITS1-5.8S-ITS2序列长度均为699 bp,其中18S rRNA基因3′端序列54 bp,ITS1序列215 bp,5.8S rRNA基因序列162 bp,ITS2序列222 bp,26S rRNA基因5′端序列46 bp。根据排序比较,川芎原植物与其商品药材间的matK基因和ITS基因序列完全相同,而川芎与日本川芎间matK基因则仅有1个变异位点,即在上游959 nt处1个转换替代(T→C),反映在氨基酸序列则发生一个非同义取代V(GTG)→A(GCG);ITS基因也仅有1个变异位点,即在ITS1上游54 nt处1个转换替代(T→C)。结论通过进化速率较快的基因序列同源性分析,基本可以认为中日所产川芎基原一致,日本川芎学名似应改为Ligusticum chuanxiong Hort.。     

VDD Pacing with a Previously Implanted Single Lead System

Three patients who had undergone implantation of a rate modulated, afrial sensitive RS4 pacemaker, with a single orthogonal lead underwent replacement of a depleted unit with a DDD pulse generator, reusing the original lead with an adapter that allowed conversion of the bipolar atrial electrode into unipolar configuration. The mean atrial electrogram amplitude was 1,8 mV and no significant atrial sensing defects were found during Holler monitoring. As the RS4 pulse generator is no longer available, continued VDD pacing is possible by replacing it with a DDD pulse generator using the previously implanted single lead system.