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.     

RELATIONSHIP BETWEEN GENETIC POLYMORPHISM OF CYP2E1 AND ALDH2, AND POSSIBLE SUSCEPTIBILITY TO ALCOHOLISM

In 45 healthy Japanese volunteers, it was found that personsheterozygous for ALDH2 (ALDH2^*1/ALDH2^*2), and also either heterozygousor mutant homozygous for CYP2E1 (C₂/C₂ or C₁/C₂ can drink muchmore alcohol, even with (slight) flushing, than persons heterozygousfor ALDH2 (ALDH2^*1/ALDH2^*2) and normal homozygous for CYP2E1(C₁/C₁)     

Contact pressure distribution features in Down syndrome infants in supine and prone positions, analyzed by photoelastic methods

BACKGROUND: Local force distribution supporting the bodyweight of infants with Down syndrome (DS) appears to be different from that of healthy controls. The purpose of the present study was to establish methods to assess this force distribution and to allow therapeutic evaluation of neurological development in DS infants prior to walking. METHODS: Contact pressure distribution patterns in supine and prone positions were measured by photoelastic methods and were compared between DS infants and healthy controls. The DS group included eight subjects, seven with regular trisomy 21, and one with a Robertson translocation. The controls consisted of 14 neonates, four 4-month-old infants and eight 7-month-old infants. RESULTS: In both groups, head loading ratio decreased as age advanced but the decrement was less in the test group than in the control group. When the bodyweight loading ratios were measured in two different lying positions, that is, prone and supine, the ratios for prone generally tended to be smaller than those for supine in the controls. This kind of difference between prone and supine was not seen in the DS group. The bodyweight is somewhat sustained with limbs and the limbs loading ratios in the DS group were always significantly lower than in the controls. CONCLUSION: Coordinated development of weight-supporting limbs seems to be poor in the DS group.     

Occupational Factors and Problem Drinking among a Japanese Working Population

Problem drinking is a serious public health problem in the workplace. However, few Japanese epidemiological studies have investigated the occupational characteristics of problem drinking. The purpose of this study is to clarify the occupational risk factors for problem drinking among a Japanese working population. We used data from a random-sampling survey about mental health and suicide, conducted among Hamamatsu City residents aged 15 to 79 yr old during May and June in 2008. The relation between occupational factors and problem drinking was analyzed with multiple logistic regression models stratified by gender. CAGE questionnaire was used to assess problem drinking. With regard to employment types, problem drinkers were more prevalent among self-employed women. With regard to occupational types, clerical and service professions had more problem drinkers of either sex, while administrative/managerial and sales professions had more women with such problem. With regard to company size, male problem drinkers were more prevalent in smaller companies than in larger ones. These results indicate that the prevalence of problem drinkers in the workplace depends on where one works. It is necessary to consider these characteristics to provide effective measures to address problem drinking in the workplace.     

Altered intrahepatic pathway of para-umbilical vein in portal hypertension

The object of this study was to determine the frequency and characteristics of altered paraumbilical vein in the hepatic parenchyma, developed from portal hypertension, using computed tomography (CT). Two hundred and ninety-two patients who presented with portal hypertension from 1986 to 1996 were studied retrospectively. The pathway of the dilated para-umbilical vein was demonstrated by contrast-enhanced CT. Thirty-one (11%) patients had a dilated para-umbilical vein arising from the left portal vein into the falciform ligament. In 24 (77%) of these patients, the para-umbilical vein followed the expected route, passing through the fissure of ligamentum teres hepatis. The remaining seven patients (23%) displayed the unusual pathway, with the vein arising from the left branch of the portal vein and passing into the hepatic parenchyma. In these seven patients, four had one collateral vein, and three patients had two collateral veins in the liver parenchyma. The dilated para-umbilical vein frequently passes through the hepatic parenchyma in patients with portal hypertension.     

Tripterygium glycosides suppress production of interleukin‐4 by splenocytes in oxazolone‐induced murine colitis

OBJECTIVE: To investigate the in vitro effect of Tripterygium glycosides (TG) on cytokine production by splenocytes in oxazolone (OXZ)‐induced colitis in mice. METHODS: Oxazolone (6 mg in 50% ethanol) was administered to male SJL/J mice intrarectally to induce colitis and the mice were killed 3 days later. Isolated splenocytes were cultured for 24 h in the presence of phorbol myristate acetate and ionomycin. A preparation of Tripterygium glycosides at a concentration of either 0.1 mg/mL or 0.01 mg/mL was added to the culture medium of splenocytes. Production of interferon gamma (IFN‐γ) and interleukin‐4 (IL‐4) in the supernatant were measured by ELISA. RESULTS: Production of IFN‐γ in the normal control group was suppressed by TG at both concentrations (0.01 and 0.1 mg/mL; 1.24 ± 0.13 pg/mL (samples without TG) → 0.97 ± 0.26 pg/mL (0.01 mg/mL TG) → 0.87 ± 0.18 pg/mL (0.1 mg/mL TG); P < 0.02) in a dose dependent manner. In the OXZ‐induced colitis group, the basic level of IFN‐γ was significantly lower than that of the normal control group (1.24 ± 0.13 pg/mL vs 0.65 ± 0.08 pg/mL; P < 0.01); but IL‐4 production was significantly increased in the OXZ‐induced colitis without TG group (7.83 ± 0.69 pg/mL vs 5.65 ± 0.48 pg/mL, P < 0.01). In both groups, TG suppressed IL‐4 production in a dose‐dependent manner (normal control group: 5.65 ± 0.48 pg/mL (samples without TG) → 4.97 ± 0.38 pg/mL (0.01 mg/mL TG) → 3.98 ± 0.32 pg/mL (0.1 mg/mL TG), P < 0.01; OXZ group: 7.83 ± 0.69 pg/mL (samples without TG) → 7.07 ± 0.47 pg/mL (0.01 mg/mL TG) → 6.35 ± 0.48 pg/mL (0.1 mg/mL TG), P < 0.01). CONCLUSION: Oxazalone‐induced IL‐4 overproduction by splenocytes was significantly suppressed by TG in a dose dependent manner and the beneficial effects of TG on ulcerative colitis might be related to the suppression of the Th2 type (e.g. IL‐4) mediated immunological response of splenocytes.     

Electroanatomical Mapping‐Guided Endocardial and Epicardial Ablation of Sustained Ventricular Tachycardia Originating From Alcohol Septal Ablation‐Induced Scar in a Patient With Hypertrophic Obstructive Cardiomyopathy

Ventricular Tachycardia After Alcohol Septal Ablation. A 76‐year‐old female developed 2 different ventricular tachycardias (VTs) 5 years after alcohol septal ablation (ASA) for symptomatic hypertrophic obstructive cardiomyopathy. VT#1 was a small macroreentry at the anterior border of the low‐voltage zone, suggesting the ASA‐scar and eliminated by endocardial ablation at a site recording fractionated potentials covering the mid‐diastolic and presystolic periods. VT#2 was a focal VT and eliminated by epicardial cryoablation at the basal posterior left ventricle, suggesting the posterior border of the ASA‐scar. Using the electroanatomical mapping, we demonstrated that the mechanism of the VTs was reentry at the edge of the ASA‐scar. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1296‐1299, November 2010)