Down-regulation of inducible nitric oxide synthase (iNOS) in rat with congenital hydronephrosis

BACKGROUND: Most of our knowledge concerning obstructive uropathy has been derived mainly from surgically manipulated animal models, and the pathogenesis of congenital obstructive hydronephrosis is not fully elucidated. Nitric oxide (NO) acts as an important biological modulator with diverse physiological functions, which can be either toxic or protective depending on the situation. NO is synthesized from l-arginine by nitric oxide synthase, and in the kidney iNOS is expressed spontaneously. The aim of our study is to investigate the expression of iNOS protein and its relationship with tubulointerstitial fibrosis and tubular cell apoptosis in congenital hydronephrosis. METHODS: We conducted histological studies on 18 kidneys of six-week-old-rats from an inbred colony of congenital hydronephrosis with reference to the histological grading of the affected kidney, tubulointerstitial fibrosis, renal tubular atrophy, and tubular cell apoptosis. Renal transforming growth factor-beta1 (TGF-beta1) level was determined by a sandwich ELISA assay and the expression of iNOS was analyzed by western blotting. RESULTS: Most of the hydronephrotic kidneys were markedly enlarged with dilatation of the collecting system, parenchymal thinning, tubular atrophy, interstitial infiltration and fibrosis. Renal TGF-beta1 level was higher in hydronephrotic kidneys than normal control kidneys (364.81 +/- 52.60 vs. 221.19 +/- 22.53 pg/mg protein, P < 0.05). Tubular apoptotic score in hydronephrotic kidneys was also significantly higher than in the normal control kidneys (1.97 +/- 0.42 vs. 0.14 +/- 0.02/HPF, P < 0.01). The expression of iNOS protein was lower in the affected kidneys compared with the normal control kidneys (8.79 +/- 0.78 vs. 14.00 +/- 0.83 arbitrary unit, P < 0.01). There was a negative correlation between iNOS expression and histological grading in congenital hydronephrosis. The iNOS expression also correlated negatively with renal interstitial fibrosis, TGF-beta1 level and tubular cell apoptosis. CONCLUSION: Our study confirmed the down-regulation of iNOS expression in affected kidneys from rats with congenital hydronephrosis, in which the cytoprotective effect of NO may be lost or weakened.     

Prevalence of hepatitis C virus antibody in an area endemic for hepatitis B virus and human T cell leukaemia virus

To clarify the prevalence of concurrent infection with hepatitis C virus (HCV), hepatitis B virus (HBV) and human T cell leukaemia virus (HTLV), we measured HCV antibody in the population of a district endemic for HBV and HTLV infection. Blood samples were collected in June 1990 from 579 inhabitants of four islands of Uwa Bay in the southwest of Ehime Prefecture in Japan. Anti-HCV antibody against C100-3 protein was detected using an enzyme-linked immunosorbent assay kit (Ortho Diagnostics). Thirteen of the 579 inhabitants (2.2%) were positive for anti-HCV, and this prevalence rate was not significantly different from the frequency of anti-HCV in Tokyo blood donors. A total of 11% (64 of 579) of the subjects were positive for HBsAg and 3.3% (19 of 579) were positive for anti-HTLV. These frequencies of HBsAg and anti-HTLV positivity were distinctly higher than the respective means of Japanese. All anti-HCV positive individuals were negative for HBsAg and anti-HTLV, while 54% (7 of 13) had increased alanine aminotransferase levels. These data suggest that the prevalence of HCV infection is not high even in an area endemic for HBV and HTLV infection.     

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.     

The Preclinical Safety Evaluation of Human Monoclonal Antibody against Cytomegalovirus

The human monoclonal antibody against cytomegalovinis (Mab C23)was examined pharmacokinetically and toxicologically as partof the preclinical studies prior to approval for human use.Rats given repeated intravenous administrations of Mab C23 producedno antibodies against Mab C23 and maintained a blood Mab C23level in a dose-dependent manner. However, pregnant rabbitsproduced antibodies against Mab C23. The half-life of Mab C23in plasma was 15.9 days in rats, which was similar to that ofnormal human serum -globulin (NHSG). Neither behavioral effectsnor circulatory disturbance was found in mice, rats, and dogseven after a single intravenous injection of 100 or 200 mg/kg,which corresponds to 50 or 100 times the intended clinical dosage.The repeated doses of 2, 10, or 20 mg/kg of Mab C23 on six occasionswith 1- or 2-week intervals elicited a transient decrease inleukocyte counts in rats given 10 or 20 mg/kg, but no adverseeffects in cynomolgus monkeys. Mab C23 did not cause any reproductiveor developmental toxicity when administered to rats and rabbitsat dose levels of 20 mg/kg or less. However, pregnant animalsshowed lower plasma levels of Mab C23 than non-pregnant animals.The chromosomal aberration test disclosed no clastogenicityin human lymphocytes. An immunostaining for Mab C23 revealedno localizations in several tissues of cynomolgus monkeys givenintravenous doses of Mab C23. The preclinical safety evaluationin animals other than rabbits, which produced no antibodiesagainst Mab C23, showed that the behavior of Mab C23 is pharmacokineticallysimilar to that of NHSG and is as safe as NHSG, which has longbeen used as a biological agent. However, because there wasa difference in blood levels of Mab C23 between pregnant andnonpregnant animals, its clinical administration to pregnantpatients should differ from that to non-pregnant patients.     

Assessment of body composition measured by bioelectrical impedance in children

Bioelectorical impedance methods have been found to be a valid and reliable way of estimating per cent body fat (%BF) in adults. We applied them to healthy children and compared them with conventional anthropometry methods. One thousand two hundred and sixteen children participated in this study. Impedance and skinfold thickness were measured, and %BF was estimated using these values. Bodyweight and height were measured, and per cent obesity (%OB) and body mass index (BMI) were obtained. The values of %BF by the bioelectrical impedance method (%BFi) were 8.6 ± 4.0% in the junior male group, 14.2±2.8% in the junior female group, 7.9±4.7% in the senior male group and 16.1 ±2.9% in the senior female group. The % BFi correlated strongly with skinfold thickness, %OB and BMI. Thus %BFi correlated strongly with variables from conventional methods. It was concluded that it is a reliable way of assessing lipid storage in children.     

Continuing Medical Education Program in Journal of Cardiovascular Electrophysiology

Article Title:  The Work-Up and Management of Patients with Apparent or Subclinical Cardiac Sarcoidosis: With Emphasis on the Associated Heart Rhythm Abnormalities.     

Two cases of sleep-disordered breathing in climacteric

Abstract Two cases of sleep disordered-breathing in climacteric were reported. Polysomnography including esophageal pressure (Pes) measurement was performed. Case 1 was diagnosed as upper airway resistance syndrome. Case 2 was diagnosed as obstructive sleep apnea syndrome, while many episodes of upper airway resistance also existed. Hormone replacement therapy improved clinical symptoms, and in case 1, Pes nadir was improved but incidence of arousals which was induced by breathing disturbances was not significantly changed. Sleep disordered-breathing should be suspected as a cause of sleep disorder even in females, especially in climacteric age. Pes measurement and evaluation of arousals is required. Hormone replacement therapy may release the upper airway resistance.     

Alcohol effect on sleep electroencephalography by fast Fourier transformation

Abstract The influence of alcohol (ethanol) on sleep was investigated in 10 men. Polysomnography (PS) was recorded on a baseline night (BL-N) and an ethanol (0.8 g/kg) night (Et-N). On visual score rapid eye movement (REM) sleep was reduced, REM latency was prolonged on Et-N as compared to BL-N. Using the fast Fourier transformation method, electroencephalographic power density of REM sleep in δ frequencies band and in the 10–12 Hz range of non-REM sleep were enhanced. REM sleep and non-RJEM sleep changes were prominent in the second-half and first-half of the night, respectively.     

The differences of self-ratings of sleep quality associated with epinephrine and wake time during 4 hour sleep

Abstract The present study examined the differences of self-ratings of 4h sleep in three states: L-WE, where the percentage of waking time and urinary epinephrine are low (< 20% waking time); H-W, where the percentage of waking time and epinephrine levels increase along the basal regression line as determined by a previous study (20–100% waking time and < 7 ng/min); H-E, where epinephrine levels increase more than expected from the basal regression line for the two parameters (> 7 ng/min). Eight healthy male subjects participated twice in a 4 h polysomnograph experiment with four types of sleep onset (total of 64 observations). In group L-WE (52 observations for eight subjects), there were no excessively negative feelings on sleep latency, sleep depth, and feelings of sleep compared with usual sleep according to the questionnaire. Subjective sleep diagrams in group L-WE were similar to polysomnographic findings. Thus, group L-WE was thought objectively and subjectively to have a good sleep state. Groups H-W (eight observations for four subjects) and H-E (four observations for two subjects) had negative feelings regarding sleep depth and feelings of sleep compared with usual sleep. Approximately half the group H-W underrated their sleep compared with objective diagrams, while all cases in group H-E remarkably underrated their sleep in the subjective diagrams. The state of remarkable adrenal medullary secretory activity seen in group H-E and that of the slightly increased activity shown in group H-W were included in poor sleep states objectively and subjectively.