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.     

Significance of lateral biopsy specimens during transrectal ultrasound-guided prostate biopsies in Japanese men

OBJECTIVES: Lateral biopsies are thought to have a better cancer detection rate compared with standard sextant biopsies. This study aimed to determine whether lateral peripheral zone biopsies in Japanese men who underwent transrectal ultrasound-guided prostate biopsies provided a significantly higher cancer detection rate than sextant biopsies. METHODS: Between 1999 and 2004, data were collected from 461 men who underwent prostate biopsy and had enough data regarding the performance of lateral biopsies for statistical analysis. There were two categories in this study: (i) patients who underwent sextant prostate biopsies; and (ii) patients who underwent sextant biopsies plus lateral biopsies. RESULTS: Prostate cancer was detected in 141 (30.6%) of 461 patients. It was detected in 24 (22.2%) of 108 patients who underwent sextant biopsies and 117 (33.1%) of 353 patients who underwent sextant plus lateral biopsies. Lateral biopsies were not associated with a statistically higher rate of positive biopsy findings; however, we found a significantly higher ratio of patients with positive findings in those with prostate specific antigen (PSA) levels 10 ng/mL (one of 71, 1.4%) among those who had positive cores only in lateral biopsy samples (P < 0.0001). CONCLUSIONS: Lateral biopsies did not show a significantly higher detection ratio of prostate cancer compared to sextant biopsies. However, lateral biopsies were more effective than sextant biopsies in patients with lower PSA levels. Our findings might be useful for the establishment of biopsy strategies to detect prostate cancer, especially in patients with lower PSA levels.     

Does H2-receptor antagonist alter the renal function of cyclosporine-treated kidney grafts?

Histamine-type 2 antagonists (H₂-blockers) as represented by cimentidine have been shown to adversely affect renal allograft function, particularly when coadministered with cyclosporine, currently a major immunosuppressant. To determine whether or not a newer and more powerful H₂-blocker, famotidine, would produce similar adverse effects, we assessed seven cyclosporine-treated renal allograft recipients with regard to changes in their renal function on or off the H₂-blocker over a one-week period. Neither the administration nor withdrawal of famotidine (20–40 mg/day) resulted in any significant changes in serum creatine, BUN, urine output or cyclosporine trough levels, suggesting that famotidine can be safely administered as an H₂-blocker to cyclosporine-treated renal allograft recipients.     

N-acetylaspartate is an axon-specific marker of mature white matter in vivo: a biochemical and immunohistochemical study on the rat optic nerve.

Axonal pathology is a major cause of neurological disability in multiple sclerosis. Axonal transection begins at disease onset but remains clinically silent because of compensatory brain mechanisms. Noninvasive surrogate markers for axonal injury are therefore essential to monitor cumulative disease burden in vivo. The neuronal compound N-acetylaspartate, as measured by magnetic resonance spectroscopy, is currently the best and most specific noninvasive marker of axonal pathology in multiple sclerosis. The possibility has been raised, however, that N-acetylaspartate is expressed also by oligodendroglial lineage cells. In order to investigate N-acetylaspartate specificity for white matter axons, transected rat optic nerves were analyzed by high-performance liquid chromatography and immunohistochemistry. In transected adult nerves, N-acetylaspartate and N-acetyl aspartylglutamate decreased in concordance with axonal degeneration and were undetectable 24 days posttransection. Nonproliferating oligodendrocyte progenitor cells, oligodendrocytes, and myelin were abundant in these axon-free nerves. At 24 days posttransection, N-acetylaspartate was increased (42%; p = 0.02) in nontransected contralateral nerves. After transection at postnatal day 4, total N-acetylaspartate decreased by 80% (P14; p = 0.002) and 94% (P20; p = 0.003). In these developing axon-free nerves, 25 to 33% of oligodendrocyte progenitor cells were proliferating. These data validate magnetic resonance spectroscopy measurements of N-acetylaspartate as an axon-specific monitor of central nervous system white matter in vivo. In addition, the results indicate that neuronal adaptation can increase N-acetylaspartate levels, and that 5 to 20% of the N-acetylaspartate in developing white matter is synthesized by proliferating oligodendrocyte progenitor cells.