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.     

Experimental myelitis caused by herpes simplex virus type 2 in C57BL/6N and BALB/cN mice

Intraperitoneal and intracranial inoculation of herpes simplex virus type 2 (HSV 2) into BALB/cN and C57BL/6N mice was carried out to induce experimental myelitis. The myelitis was clearly observed in C57BL/6N mice following intraperitoneal inoculation. Within 24 hours before death, the mice showed urinary and rectal incontinence and paraplegia of the hind legs. Randomly distributed, severe necrosis was demonstrated in the spinal cord, mainly at the lower cord. In BALB/cN mice the clinical symptoms were not clearly observed, as the mice died shortly after their onset. Although spinal cord necrosis was more prominent in C57BL/6N mice than BALB/cN mice, brain necrosis was only found in the latter, and not in the former. Both strains of mouse showed marked nuclear pyknosis of the nerve cells and slight nuclear pyknosis of the astrocytes in the brain where HSV 2 antigen was demonstrated immunohistochemically. The antigen was also detected in the necrotic spinal cord. In contrast, intracranial inoculation of the virus into both strains did not cause myelitis. Spinal cord necrosis was not demonstrated and virus DNA was not detected, by PCR, in spinal cord samples. In the brain, however, the virus was demonstrated by both PCR and immunohistochemistry.     

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.     

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.     

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.     

Adequacy of Pacing Rate During Exercise in Rate Responsive Ventricular Pacing

Our objective was to determint; the adequate pacing rate during exercise in ventricular pacing by measuring exercise capacity, cardiac output, and sinus node activity. Eighteen patients with complete AV block and an implanted pacemaker underwent cardiopulmonary exercise tests under three randomized pacing rates: fixed rate pacing (VVJ) at 60 beats/min and ventricular rate-responsive pacing (VVIR) programmed to attain a heart rate of about 110 beats/min ar 130 beats/min (VVIR 110 and VVIR 130, respectively) at the end of exercise. Compared with VVI and VVIR 130, VVIR 110 was associated with an increased peak oxygen uptake(VVIR 110:20.3 ± 4.5 vs VVI: 16.9 ± 3.1; P < 0.01; and VVIR 130: 19.0 ± 4.1 mL/min per kg, respectively; P < 0.05) and a higher oxygen uptake at anaerobic threshold (15.3 ± 2.7, 12.7 ± 1.9; P < 0.01, and 14.6 ± 2.6 mL/min per kg; P < 0.05). The atrial rate during exercise expressed as a percentage of the expected maximal heart rate was lower in VVIR 110 than in VVI or VVIR 130 (VVIR 110: 75.9%± 14.6% vs VVI: 90.6%± 12.8%; P < 0.01; VVIR 110 vs VVIR 130: 89.1%± 23.1%; P < 0.05). There was no significant difference in cardiac output at peak exercise between VVIR 110 and VVIR 130. We conclude that a pacing rate for submaximal exercise of 110 beats/min may be preferable to that of 130 beats/min in respect to exercise capacity and sympathetic nerve activity.