Antiproliferative and proapoptotic effects of tocopherol and tocol on activated hepatic stellate cells.

Activated hepatic stellate cells (HSCs) play crucial roles in liver fibrosis. In the course of liver injury, HSCs, which reside in perisinusoidal spaces and lose lipid droplets, morphologically change into a myofibroblastic phenotype and acquire an increased proliferation activity in what is known as the activated state. We have investigated therapeutic strategies for liver fibrosis by promoting spontaneous reversion or inducing apoptosis in activated HSCs. Vitamin E consists of four tocopherols and four tocotrienols, all of which are well-known antioxidants. In this study, the antiproliferative and proapoptotic effects of a tocol, which lacks methyl groups attached to the chromanol ring, and four tocopherols were investigated using activated HSCs. δ-Tocopherol and tocol exhibited relatively high proliferation inhibitory and proapoptotic abilities. However, they did not show proliferation inhibition ability on primary hepatocytes or HepG2 cells. Significant cell detachment was also observed in δ-tocopherol- and tocol-treated HSCs. Decreased protein expressions of α-smooth muscle actin and ß1 integrin were observed in a dose-dependent manner. These results indicate that δ-tocopherol and tocol induce anoikis in activated HSCs.

Evaluation of anorectal function in patients with tethered cord syndrome: saline enema test and fecoflowmetry.

OBJECT: Disturbance in anorectal function is a major factor restricting the activities of daily living in patients with spinal cord disorders. To detect changes in anorectal motilities due to a tethered spinal cord, anorectal functions were evaluated using a saline enema test and fecoflowmetry before and after patients underwent untethering surgery. METHODS: The bowel functions in five patients with a tethered cord syndrome (TCS) were evaluated by performing a saline enema test and fecoflowmetry. The contractile activity of the rectum, the volume of infused saline tolerated in the rectum, anal canal pressure, and the ability to evacuate rectal content were examined. The characteristic findings in anorectal motility studies conducted in patients with TCS were a hyperactive rectum, diminished rectal saline-retention ability, and diminished maximal flow in saline evacuation. A hyperactive rectum was considered to be a major contributing factor to fecal incontinence. In one asymptomatic patient diminished anal squeezing pressure was exhibited and was incontinent to liquid preoperatively, but recovered after surgery. Two patients who underwent surgery for myeloschisis as infants complained of progressive fecal incontinence when they became adolescents. In one patient fecal incontinence improved but in another patient no improvement was observed after untethering surgery. CONCLUSIONS: Fecodynamic studies allow the detection of neurogenic disturbances of the anorectum in symptomatic and also in asymptomatic patients with TCS. More attention should be paid to the anorectal functions of patients with TCS.

Renal focal tubulointerstitial fibrosis with short bowel syndrome: report of a case.

We report a male patient with short bowel syndrome (SBS) and renal focal tubulointerstitial fibrosis (FTIF). Seven years after surgery, he was introduced to us due to severe undernutrition, an impairment of growth hormone (GH) secretion, and abnormally low levels of plasma citrulline and arginine at 11 years 7 months of age, just before nutritional support using total parenteral nutrition (TPN) was begun. Thereafter, the support was changed to home TPN with GH supplementation. After an improvement of the disorders, GH was stopped at 17 years 3 months of age. However, hyperuricemia appeared and a renal biopsy revealed FTIF at 20 years of age. Home TPN was continued twice a week because the plasma arginine level was still low. His follow-up biopsy at 23 years of age showed morphometric amelioration. Arginine deficiency following SBS may be associated with FTIF. The cause of hyperuricemia after SBS therefore needs to be investigated in detail.

Evaluation of anorectal functions of children with anorectal malformations using fecoflowmetry.

BACKGROUND/PURPOSE: A simple and objective method evaluating the bowel functions of patients with anorectal anomalies is necessary. The authors applied fecoflowmetry and saline enama test for patients with anorectal anomalies to evaluate the fecodynamics and anorectal motilities in these children. METHODS: The bowel functions of 16 patients who underwent repair for anorectal malformations and 5 normal controls were evaluated by saline enema test and fecoflowmetry. The correlations between the clinical scores for the bowel functions and the parameters in fecodynamic studies were investigated. RESULTS: Seven of 16 patients exhibited periodical contractions of the rectum synchronized with relaxations of the anal canal during saline infusion as did the controls and had significantly higher clinical scores than the other patients. Two patients with severe chronic constipation lacked rectal contractions. Among the fecoflowmetric parameters, the maximum flow, average flow, and tolerable volume of saline infused into the rectum were significantly lower in the patients with low clinical scores than those of the controls. The maximal squeeze pressure and resting anal pressure were not significantly different between the patients and controls. CONCLUSION: Fecodynamic studies, such as fecoflowmetry and saline enema test, help in obtaining clinical indicators for the bowel functions of patients with anorectal anomalies.