Functional mechanism underlying cyclooxygenase-2 expression in rat small intestine following administration of indomethacin: Relation to intestinal hypermotility

Background and Aim:  We recently reported that cyclooxygenase (COX)-2 is upregulated in the rat small intestine after administration of indomethacin, and this may be the key to non-steroidal anti-inflammatory drug (NSAID)-induced intestinal damage. The present study investigated the mechanism for COX-2 expression induced in the rat small intestine by indomethacin, in relation with ulcerogenic processes.
Methods:  Animals were given indomethacin or SC-560 p.o., and the intestinal mucosa was examined 24 h later.
Results:  Indomethacin caused hemorrhagic lesions in the small intestine, accompanied with an increase in intestinal motility, bacterial invasion and inducible nitric oxide synthase (iNOS) activity, as well as the expression of COX-2 mRNA in the mucosa. Although SC-560 did not cause any damage, this agent caused intestinal hypermotility, the bacterial invasion and the upregulation of COX-2 expression. The mucosal PGE₂ content was decreased by SC-560 at 3 h but recovered 12 h later, and this recovery of PGE₂ was attenuated by both atropine and ampicillin, in addition to rofecoxib. The intestinal hypermotility response to indomethacin was prevented by both 16,16-dimethyl PGE₂ and atropine, but not ampicillin. Yet all these agents inhibited not only the bacterial invasion but also the expression of COX-2 and iNOS activity in the intestinal mucosa following indomethacin treatment, resulting in the prevention of intestinal lesions.
Conclusion:  These results suggest that COX-2 expression in the intestinal mucosa following the administration of indomethacin is associated with intestinal hypermotility and bacterial invasion. The intestinal hypermotility caused by COX-1 inhibition may be a key to COX-2 expression after administration of NSAIDs and their intestinal ulcerogenic properties.     

Colonic pseudolipomatosis, microscopically classified into two groups

Background: Colonic pseudolipomatosis is rare and the pathogenesis is controversial. The purpose of the present paper was to clarify endoscopic and histological characteristics of colonic pseudolipomatosis and to discuss the etiology. Methods: A total of 15 lesions from 14 patients was reviewed. They were able to be histologically classified into two groups on the basis of variety in size of the vacuoles: Group A, the ratio of largest vacuole to smallest vacuole in size is less than three, Group B, the ratio is more than four. Results: Four of 15 lesions were group A, and were endoscopically polypoid or flat lesions covered with normal‐looking mucosa. They were microscopically characterized by (i) predominant location in the upper portion of the lamina propria; (ii) no submucosal involvement; (iii) less variation in vacuolar size; and (iv) no association with lymph follicles. The vacuoles of group A contained proteinaceous materials in two of four lesions. Group B (11 lesions) had small elevated mucosa with normal‐looking surface or non‐elevated reddish mucosa. Microscopically, the lesions were mainly located in the lower portion of the lamina propria, occasionally also in the submucosa, had variable‐sized vacuoles, and were related to lymph follicles. Conclusion: It is suggested that the vacuoles in group A contain fluid, and may indicate an abnormal stagnation of interstitial fluid. Microscopic appearance of group B is essentially similar to that of pneumatosis coli. It is thought that group B probably results from penetration of gas from the crypts into the mucosa during colonoscopy. It is unclear why group B had a preference for ileocecal valve and an association with lymph follicles.     

RETARDED MESANGIAL TRANSPORT AND ITS PATHOMORPHOLOGIC SEQUELAE IN HUMAN AND EXPERIMENTAL RENAL DISEASES

Human renal biopsy specimens (472 cases) from varied kidney diseases, especially minimal glomerular change group and other idiopathic glomerular diseases having nephrotic manifestation of mainly juvenile individuals, showed morphologic evidence of paraarterial deposits of afferent arterioles at the glomerular entrances in more than 50% of examined cases. Because these deposits were often accompanied with concomitant mesangial, intraarterial and subendothelial deposits of afferent arterioles, it was felt that retarded mesangial transport which is ordinarily associated with certain glomerular diseases might be an important factor to produce these particular paraarterial deposits. The referred deposits of minimal glomerular change group cases were thought to predispose the occurrence of focal sclerotic capillary lesions at the vascular poles of glomeruli. The experimental chronic nephrotic rats produced by daily administration of aminonucleoside of puromycin revealed mesangial dysfunction with increased uptake and retarded disposal of secondarily overloaded aggregated human gamma globulin at mesangial areas in glomeruli. Besides, the increased deposits of autologous serum proteins in mesangial areas and arteriolar walls were common findings in those rats, and these deposits were observed to be always preceded to the occurrence of segmental sclerotic changes of glomeruli, which were often associated in the later stage of this experiment. ACTA PATHOL. JPN. 33: 219∼236, 1983.     

Developmental changes in electroencephalogram for term and preterm infants using an autoregressive model

The purpose of the present study was to clarify the developmental changes of electroencephalogram (EEG) background activity in term and preterm infants that take place with increasing conceptional age (CA) through an autoregressive (AR) model. Polygraphical EEG recordings were obtained from 76 healthy term and preterm infants with a CA ranging between 31 and 40 weeks. Decreases in total power and component power of δ were noted with CA during burst activity (BA) in quiet sleep (QS) and during active sleep (AS). Increases in total power and component power of δ were noted with CA during interburst interval activity (IBIA) of QS. Regression analysis (RA) of the information amount (IA) indicated a negative correlation with increasing CA in AS and in the monopolar EEG tracings Fp1, C3, O1 and O2 in BA, and a positive correlation in O1 in IBIA. Regression analysis of the IA of δ indicated a negative correlation with increasing CA in AS and in Fp1, C3, O1 and O2 in BA, and a positive correlation in O1 in IBIA. Regression analysis of the IA of δ indicated a negative correlation with increasing CA in BA and AS. These results showed that the high voltage slow wave component changed to a low voltage slow one with development in AS and that BA was longer in duration and lower in power with increasing CA, while IBIA was shorter in duration and higher in power. In conclusion, significant developmental changes occur in all derivatives of AS. Even though the EEG of BA and IBIA change separately, they are followed by EEG of QS in a continuous pattern.     

Congenital chylothorax in a patient with 21 trisomy syndrome

A female infant with 21 trisomy syndrome associated with congenital chylothorax was reported. She was born at a gestational age of 34 weeks by Cesarean section because of fetal hydrothorax and hydrops fetus, confirmed by ultrasonography at 32 weeks. Emergent resuscitation and immediate thoracentesis were performed soon after birth. After beginning breast feeding, the serous pleural fluid became opalescent and a diagnosis of congenital chylothorax was made. Feeding was changed to medium-chain triglyceride (MCT) feeding and the production of pleural effusion disappeared after thoracentesis was performed several times. Accumulating evidence suggested that MCT feeding and intermittent thoracentesis under echo guide were effective. Some reports on patients, including this one, suggest that there may be more patients with 21 trisomy associated with congenital hydrothorax. Therefore, congenital hydrothorax might be listed as a complication of 21 trisomy.     

Testicular torsion: Usefulness of contrast-enhanced power Doppler sonography

A 13-year-old-boy with suspected left testicular torsion was referred to our institute. During preparation, a significant decrease of signals on the left testis was found, however, slight blood flow was detected by the ultrasound examination enhanced by Levovist. As a result of the examination we left the testis intact, although the color of the testicular parenchyma remained black. One year after the surgery, an ultrasound examination was done again and good vascurality was observed.     

The real status of sudden infant death (SIDS) in forensic medicine

To comprehend the real status of sudden infant death syndrome (SIDS) in forensic medicine, a statistical study was conducted on 156 cases subjected to medico-legal autopsies at university medical schools throughout Japan from 1987 to 1991 and diagnosed as SIDS. Furthermore, 138 cases that had been subjected to autopsies at the Tokyo Medical Examiner's Office and given the diagnosis of SIDS were evaluated for comparison. It was noted that the incidence of SIDS diagnosed at each facility has increased.     

Prognosis of the middle-aged and aged patients with obstructive sleep apnea syndrome

Abstract The long-term natural course of obstructive sleep apnea syndrome (OSAS) is studied in order to determine whether severity of nocturnal oxygen desaturation associated with apnea/hypopnea, body mass index (BMI), and hypertension influence survival in young (<40 years), middle-aged (40–64 years), and aged (65 years) using a questionnaire survey. One hundred and forty-eight patients with OSAS aged 17–78 years (136 men, 12 women, mean 52.0±12.3 yean), who were diagnosed by standard polysomnography (PSG) between 1983 and 1993, participated in the study. The survey revealed 15 deaths and 101 survivors; 32 subjects could not be located. The survival rate was 71.4% (95% confidence interval:55.6–87.2%). The survival rate in patients with OSAS was significantly lower than that in the age and sex-adjusted control Japanese population (87.6%). In the young group, only one death (a 19–year-old woman) occurred unexpectedly during sleep. The patient showed an apnea/hypopnea index (AHI) of 33 per h and the length of time that the nocturnal oxygen saturation (SaO₂) fell below 90% (time of SaO₂ < 90%) of 205 min. The survival rate in middle-aged patients with OSAS was significantly lower than that in the age and sex-adjusted control Japanese population (79.2 vs 91.0%), but this pattern was not seen among the aged. Time of SaO₂ <90% was significantly longer in the middle-aged patients than in the aged patients, but AHI did not differ between the two groups. Moreover, it was significantly correlated with AHI in middle-aged patients, but not in the aged patients. The survival rate was significantly lower in patients with hypertension than in the patients without such complications in the middle-aged group (57.9 vs 90.4%). Cox proportional-hazard regression model including age, hypertension, BMI, AHI, lowest SaO₂, and time of SaO₂ <90% showed that hypertension was only significantly associated with lower survival rate in total group and middle-aged patients, but not in the young or aged patients. The prognosis in patients with OSAS may differ among the generations. The prognosis in the middle-aged population may depend on the role of OSAS on the complications of hypertension or severity of oxygen desaturation, but not on AHI only.     

Daytime sleepiness and automobile accidents in patients with obstructive sleep apnea syndrome

Abstract We evaluated the rate of automobile accidents and daytime sleepiness using the Epworth sleepiness scale (ESS) in 44 patients with obstructive sleep apnea syndrome (OSAS). We defined the automobile accident score as a sum of two points for every one automobile accident and one point for every near-miss accident. Automobile accidents and near-misses were found in 54.5% and 50.0% in patients with OSAS. Automobile accident score was significantly correlated with the ESS score ( r = 0.56, P < 0.01). Our findings suggest that ESS score may be useful in detecting patients with the potential risk of automobile accidents associated with daytime sleepiness.     

Deficiency of Testosterone Associates with the Substrate of Atrial Fibrillation in the Rat Model

Background: Since the prevalence of atrial fibrillation (AF) increases progressively with aging, especially in men, we hypothesized that testosterone might affect the occurrence of AF.
Methods and Results: We examined the electrophysiological properties of the atria in isolated-perfused hearts of sham-operated male (SM), female (SF), orchiectomized male with and without administration of testosterone (ORCH-T and ORCH), and ovariectomized female (OVX) Sprague-Dawley rats. An electrophysiological study revealed that repetitive atrial responses induced by electrical stimuli significantly increased in ORCH rats without changes in other electrophysiological properties and were abolished by administration of testosterone. To investigate the underlying mechanisms, we evaluated the expression level of calcium-handling proteins. In ORCH rats, the immunoreactive protein level of ryanodine receptor type 2 (RyR2) and sodium–calcium exchanger significantly increased as compared with SM and ORCH-T rats without alterations in the level of FK506-binding protein (FKBP12.6), sarcoendoplasmic reticulum Ca-ATPase, and phospholamban. Immunoprecipitation analysis demonstrated decreased binding of FKBP12.6 to RyR2 in ORCH rats, which was prevented by testosterone. In contrast, the expression levels of these proteins showed no significant differences between SF and OVX rats.
Conclusion: Deficiency of testosterone was arrhythmogenic in rat atria possibly through less binding of FKBP12.6 to RyR2, which could induce feasible calcium leakage from the sarcoendoplasmic reticulum. These results would explain, at least in part, the increase in the prevalence of AF in accordance with the decline of testosterone particularly in elderly men.