Effect of Antioxidants, Anti-inflammatory Drugs, and Histamine Antagonists on Sparfloxacin-Induced Phototoxicity in Mice

We examined the effects of antioxidants, anti-inflammatory drugs,and histamine antagonists on auricular inflammation and retinaldegeneration induced by the phototoxicity of sparfloxacin (SPFX),a quinolone antibacterial agent. Catalase (CAT), dimethyl sulfoxide(DMSO), dexamethasone (DM), indomethacin (IM), phenidone (PD),AA-861 (AA), pyrilamine maleate (PY), or cimetidine (CM) wascontinuously administered to female Balb/c mice using microosmoticpumps for 72 hr and intraperitoneally once before SPFX administration.The mice were given a single oral administration of 50 or 100mg/kg SPFX and irradiated with ultraviolet-A (UVA) light at1.5 mW/cm² for 4 hr. SPFX administration plus UVA irradiationinduced thickening and inflammation of the auricular skin andretinal degeneration in the eye. CAT and DMSO significantlyinhibited the auricular thickening only 4 hr after SPFX administration.DM, IM, and PD also inhibited this toxicity from 4 to 48 or72 hr. On the other hand, PY and CM showed no effect on thischange. With regard to the eye, CAT and DMSO completely inhibitedthe occurrence of retinal degeneration and IM and PD tendedto decrease its incidence, whereas DM, AA, PY, and CM showedno or an exacerbating effect. These results suggest that reactiveoxygen species contribute to the initiation of auricular inflammationand retinal degeneration and that cyclooxygenase products arealso involved in the initiation and later progression of auricularinflammation. They also show that histamine and 5-lipoxygenaseproducts are not involved in either phototoxic lesion.     

Extensive biopsy using a combined transperineal and transrectal approach to improve prostate cancer detection

PURPOSE: Previous studies have indicated that 6-core transrectal prostate biopsy misses a considerable number of cancers. We performed an extensive biopsy protocol of 12-core sampling using both transperineal and transrectal approaches to determine the impact on the cancer detection rate. MATERIALS AND METHODS: We prospectively evaluated 402 men who underwent 6-core transperineal and 6-core transrectal biopsies simultaneously due to abnormal digital rectal examination (DRE) and/or elevated prostate-specific antigen (PSA) levels of 4.0 ng/mL or greater. Using the transperineal approach we obtained four cores from the bilateral peripheral zone targeting the lateral and parasagittal areas and two cores from the bilateral transition zone. The following transrectal biopsy was performed traditionally. We compared cancer detection rate between the extended 12-core procedure and conventional 6-core transperineal and transrectal groups in terms of total PSA and DRE findings. RESULTS: Using the extensive combined method, prostate cancer was detected in 195 cases (48.5%) and the detection rate significantly increased 7.2% and 8.5% compared to the transperineal and transrectal groups, respectively. According to PSA levels and DRE findings, the cancer detection rate by the combined method was significantly improved in patients with PSA levels of 4-10 ng/mL and negative DRE: 10.3% and 11.6% compared to the transperineal and transrectal groups, respectively. CONCLUSIONS: The extensive 12-core method significantly improved the overall cancer detection rate and was especially efficient for men with PSA levels of 4-10 ng/mL accompanied by a negative DRE finding.     

Mucosal Tag of the Duodenum: —Report of a Case—

Abstract: We studied a 66-year-old female who had a dull epigastric pain. An upper gastrointestinal (GI) series revealed a cordlike protrusion in the duodenal region, and a gastroendoscopic examination was performed and revealed a mucosal tag (MT) about 3 cm in length in the duodenal bulb. The MT was resected endoscopically and was found to be lined by normal duodenal mucosa and to have developed hyperplasia of the Brunner's glands. This MT was considered to be a congenitally-developed, hamartomatous hyperplasia of the duodenal mucosa, and of the Brunner's glands in particular.     

>CASE REPORT: Eosinophilic colitis with high antibody titre against Ascaris suum

Eosinophilic gastroenteritis (EGE) is an inflammatory disease characterized by eosinophilic infiltration of the gastrointestinal tract accompanied by varying abdominal symptoms and usually by peripheral blood eosinophilia. Although the precise aetiology of EGE remains to be determined, contribution of allergic process to certain allergens, such as foods, drugs and parasites, has been repeatedly proposed as the pathogenesis of the disease. Here we report on a rare case of a woman who had extensive eosinophilic infiltration in the descending and rectal colon with a high titre of IgG antibody against Ascaris suum. The patient was successfully treated with prednisolone.     

PHYSIOLOGICAL SIGNIFICANCE OF APOPTOSIS DURING ANIMAL VIRUS INFECTION

Apoptosis has been considered to be a host defense mechanism against viral infection in multicellular organisms. This is based on the findings that apoptogenic mutants of insect viruses cannot grow because infected host cells die by apoptosis. This suggests that the apoptotic response of host cells has a deleterious effect on virus infection. Thus, apoptosis is an important host defense mechanism that is capable of inhibiting viral replication during infection. However, in vitro studies indicated that apoptosis alone does not provide the same protection against viral infection in animal cells as it does in the insect cells. Still, most animal viruses have acquired a strategy to overcome host cell apoptosis. In addition, a varying degree of necrosis usually accompanies apoptosis, suggesting a possible contribution of necrosis to the host reactions against virus. To understand the physiological significance of apoptosis during animal virus infection, we have characterized viral growth and the cellular responses against virus infection in a wide variety of virus-cell interaction systems. Mainly based on our own works, we discuss the nature of apoptosis in the animal virus infection and verify its role as a host defense mechanism against virus infection.     

Effects of Sho-saiko-to on the Pharmacokinetics and Pharmacodynamics of Tolbutamide in Rats

Although Sho-saiko-to (Xiao Chai Hu Tang), a major Chinese traditional medicine, is frequently prescribed with other synthetic or biotechnological drugs for the treatment of various chronic diseases, there is a dearth of information about interactions between sho-saiko-to and co-administered drugs. This paper reports the effects of Sho-saiko-to on the pharmacokinetics and glucose responses of a sulphonylurea hypoglycaemic agent, tolbutamide, after their oral administration in rats. After oral administration of tolbutamide (50 mg kg^?1) with or without Sho-saiko-to extract powder (300 mg kg^?1) to male Sprague-Dawley rats cannulated in the jugular vein, plasma tolbutamide and glucose levels were periodically measured. Co-administration of Sho-saiko-to tended to elevate the plasma tolbutamide concentration in the absorption phase. A two-compartment lag-time model was found to describe the plasma tolbutamide concentration-time data. The maximum concentration of tolbutamide was significantly increased and time to reach the maximum concentration was reduced to about 70% by co-administration with Sho-saiko-to. There was no significant change in area under the curve or in the elimination half-life of tolbutamide. The extent of the lowering effect of tolbutamide on plasma glucose levels was increased up to 0.75 h and decreased after 5 h after co-administration of Sho-saiko-to. In conclusion, these studies suggest that sho-saiko-to slightly hastens the gastrointestinal absorption of tolbutamide. Furthermore, it is considered that elevation of the gastrointestinal absorption rate by Sho-saiko-to might potentiate the hypoglycaemic effect of this sulphonylurea in the early period after oral administration.     

Extracorporeal leukocyte removal therapy for patients with ulcerative colitis

Background: The purpose of the present paper was to investigate efficacy of leukocytapheresis (LCAP) or granulocytapheresis (GCAP) in pediatric patients with ulcerative colitis (UC), including reduction of the total dose and side‐effects of corticosteroids. Methods: Courses of five Japanese adolescents with UC were analyzed. Four patients had recurrent UC with repeated remissions and exacerbations despite therapy including 5‐aminosalicylic acid in combination with a corticosteroid. The other patient had a first attack. Effectiveness of adding LCAP or GCAP was assessed with regard to short‐term changes in clinical activity, complications, and longer‐term outcome. Results: Clinical improvement was attained in three patients, while the other two did not improve and underwent colectomy. One of the two patients had moderately severe complications from LCAP and showed increased clinical activity during LCAP. The other, who began therapy with LCAP alone, had moderate improvement only after addition of a corticosteroid. Conclusion: Additional studies are needed to determine optimum timing of LCAP or GCAP and initiation of remission‐maintenance therapy.     

Cryoglobulinaemia among maintenance haemodialysis patients and its relation to hepatitis C infection

It has been shown that hepatitis C virus (HCV) infection is closely associated with mixed type cryoglobulinaemia. It is also known that HCV infection is rampant among chronic haemodialysis patients. We studied 531 renal failure patients on maintenance dialysis including 170 with positive HCV antibodies for cryoglobulinaemia, and its incidence was compared with controls which consisted of 242 chronic hepatitis C patients without renal failure and 183 healthy adults. Cryoglobulinaemia was present in 30.6% of dialysis patients with HCV infection, 10.8% of dialysis patients without HCV infection, 29.8% of patients with chronic hepatitis C without renal failure, and 0% of healthy adults. Among the 30 new renal failure patients who were started on dialysis within 6 months, four were positive for HCV antibodies, and one of them had cryoglobulinaemia; of the 26 HCV-negative patients, four (15%) were cryoglobulinaemic. The cryocrit values among dialysis patients were much lower than those of the control cases and other reports on non-dialysis cases. Patients with cryoglobulinaemia were generally younger compared with patients negative for this condition. There was no correlation between cryoglobulinaemia and past blood transfusion, underlying disease or length of dialysis. Cryoglobulinaemic patients seem to develop renal failure at relatively young ages and a considerable proportion of cryoglobulinaemic dialysis patients may have already had cryoglobulinaemia at the time of the start of haemodialysis. There was no indication that the presence of cryoglobulin in serum adversely affects the liver disease nor increases serum virus load in HCV-infected dialysis patients. Thus, it was concluded that although HCV infection has a certain role in the development of cryoglobulinaemia in dialysis patients, they develop cryoglobulinaemia less frequently and produce cryoglobulin to a lesser degree in the presence of HCV infection as compared with non-dialysis patients.     

High-dose chemotherapy and autologous blood stem cell transplantation in children with metastatic neuroblastoma

High-dose chemotherapy (HDC) followed by autologous blood stem cell transplantation (ABSCT) was performed to improve the prognosis of children with metastatic neuroblastoma over 1 year of age at diagnosis. Seven stage IV neuroblastoma patients with a median age of 3.9 years (range 1.6–11.4 years) received conventional chemotherapy before leukapheresis for ABSCT. The median duration of chemotherapy before harvest was 8 months (range 3–23 months). Peripheral blood stem cells (PBSC) were harvested from them after the use of cytotoxic drugs plus granulocyte colony-stimulating factor. The median number of granulocyte-macrophage colony forming units collected after harvest was 23.2 × 10⁴/kg (range 10.1–45.3 × 10⁴/kg). The patients were administered HDC consisting of carboplatin, etoposide, and melphalan followed by ABSCT. Hematopoietic reconstitution after ABSCT was favorable; recovery of granulocytes count > 0.5 × 10⁹/L occurred within 2 weeks and stable platelet engraftment occurred at a median duration of 23 days (range 7–33 days). The toxicity of ABSCT was well tolerable. Two of the four patients who received ABSCT at their first complete remission remained in remission 67 and 68 months after ABSCT. One with partial remission also showed a good response for 8 months. The other two at first relapse showed a transient regression of the tumor. The prognosis of seven patients who received ABSCT was significantly better than that of 13 patients who received conventional therapy alone. These findings suggest that HDC followed by ABSCT is safe and useful as consolidation therapy for the treatment of patients with metastatic neuroblastoma.