We investigated the effect of oral feeding of heat-killed Lactobacillus casei strain Shirota on immunoglobulin E (IgE) production in mice. The strain was orally administered to BALB/c mice that had been preinjected intraperitoneally with ovalbumin, and the level of IgE in serum was determined. Results indicated that the oral feeding of L. casei strain Shirota was effective in inhibiting IgE production in serum, and the IgE production in response to ovalbumin was significantly inhibited in the mice. The in vitro production of IgE by the spleen cells from mice fed L. casei strain Shirota in response to restimulation with ovalbumin was inhibited in contrast to that of spleen cells from the control group. We also examined the pattern of cytokine production by spleen cells from mice fed L. casei strain Shirota followed by restimulation with ovalbumin in vitro. In the mice fed L. casei strain Shirota, the production by the spleen cells of Th1 cell-associated cytokines, such as interferon-gamma and interleukin-2, was higher than that by the spleen cells from the control group. In contrast, the production of Th2 cell-associated cytokines, such as interleukin-4, interleukin-5, interleukin-6, and interleukin-10, by spleen cells in the group fed L. casei strain Shirota was lower than that by the cells from the control group. Furthermore, the interleukin-12 production of the spleen cells from mice fed L. casei strain Shirota was also higher than that of the control group.

Prevention of onset in an insulin-dependent diabetes mellitus model, NOD mice, by oral feeding of Lactobacillus casei. APMIS 105: [643][644][645][646][647][648][649] 1997.The effects of Lactobacillus casei (LC) on the onset of diabetes in an insulin-dependent diabetes mellitus model, nonobese diabetic (NOD) mice, were examined. From the age of 4 weeks, female NOD mice were fed a diet of either standard laboratory chow (n= 12) or the same chow containing 0.05% weight heat-killed cells of LC (n= 12), and the onset of diabetes was thereafter recorded. The incidence of diabetes in the control group (10112) was significantly higher than that in the LC-treated group (31 12) (p

Although the in£uence of selective cyclooxygenase (COX)-2 inhibitors on the proliferation of colon adenocarcinoma cells have been the subject of much investigation, relatively little research has compared the e¡ects of di¡erent COX-2 inhibitors. Celecoxib strongly suppressed the proliferation of COX-2 expressing HT-29 cells at 10^40 W WM. NS-398 and nimesulide also inhibited cell proliferation, whereas rofecoxib, meloxicam, and etodolac did not. Only celecoxib induced apoptosis of HT-29 cells, as detected on the basis of DNA fragmentation, TUNEL positivity, and caspase-3/7 activation. DNA fragmentation was also increasd in COX-2 non-expressing cell lines (SW-480 and HCT-116) by exposure to celecoxib for 6^24 h. All six COX-2 inhibitors suppressed the production of prostaglandin E 2 by HT-29 cells, suggesting that the pro-apoptotic e¡ect of celecoxib was unrelated to inhibition of COX-2. Inactivation of Akt might explain the di¡erential pro-apoptotic effect of these selective COX-2 inhibitors on colon adenocarcinoma cells.

Abstract.The antidiabetic effects of Lactobacillus casei (LC) on a non-insulin-dependent diabetes mellitus (NIDDM) model, KK-AY mice, were investigated. The oral administration of LC to male 4-week-old KK-AY mice, or raising the mice on a 0.05% LC-containing diet significantly decreased the plasma glucose at 8 to 10 weeks of age compared with the control group. The body weights of the LC-treated groups were lower than those of the control group, although the food intake was nearly the same in all groups. Phenotypic analysis of spleen cell surface markers revealed that the increase in CD4+ T cells at 12 weeks was significantly inhibited by the oral treatment with LC. Cytokine production, especially that of interferon-y and interleukin 2, was also inhibited in the oral LC-treated group. The plasma insulin levels of the LC-treated groups were also lower than those of the control group, and the insulin binding potential of red blood cells in the LC-treated mice was augmented more than that in the control group. Taken together, these findings led us to conclude that the oral administration of LC in the NIDDM model mice, KK-AY, was involved in the decrease in the plasma glucose level and modified the host immune responses.

Cladosiphon fucoidan may deserve particular attention as a safe agent that can prevent H. pylori infection and reduce the risk of associated gastric cancer.

The anti-ulcer effects of bifidobacteria, lactobacilli and streptococci were examined using the acetic acid-induced gastric ulcer and ethanol-induced erosion models in rats. Bifidobacterium breve YIT4014 and 4043, and Bifidobacterium bifidum YIT4007 were administered orally, and anti-ulcer effects were confirmed for not only these organisms but also their polysaccharide fractions (PSFs). The major component of these anti-ulcer polysaccharides was rhamnose. In particular, polysaccharides in which the rhamnose content exceeded 60% were more effective in healing gastric ulcers. After administration of the PSF from B. bifidum YIT4007, the levels of epidermal growth factor and basic fibroblast growth factor increased in gastric tissues. Similar results were observed for the culture supernatant of gastric epithelial cells cultured with PSF. Furthermore, the production of 6-ketoprostaglandin F1 alpha by macrophages was also enhanced by PSF. These results indicated that these bacteria and their polysaccharides induced host repair and protective systems in the gastric ulcer model.

These results suggested that the duration of exposure to both CPT-11 and SN-38 of the intestinal epithelium and CPT-11 plasma Cmax are closely related to the incidence and severity of CPT-11-induced delayed-onset diarrhea in rats.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce apoptosis in a variety of cell lines. In this study, we examined the effect of NSAIDs on the growth and apoptosis of synovial cells from patients with rheumatoid arthritis and analyzed the activation of peroxisome proliferator-activated receptor ␥ (PPAR␥) as a possible mechanism of action of NSAIDs. Cell proliferation and viability were assessed from 5-bromo-2Ј-deoxyuridine incorporation and by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay, respectively. The apoptosis of synovial cells was identified by DNA fragmentation assay and terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling assay. Indometacin, diclofenac, oxaprozin, and zaltoprofen reduced cell proliferation and induced apoptotic cell death in synovial cells, whereas ketoprofen and acetaminophen did not. N-[2-(cyclohexyloxyl)-4-nitrophenyl]-methanesulfonamide (NS-398), a selective cyclooxygenase-2 inhibitor, also inhibited cell proliferation, whereas it did not cause apoptosis. Rheumatoid synovial cells expressed PPAR␥ mRNA, and the PPAR␥ ligands 15-deoxy-⌬ 12,14 -prostaglandin J 2 and troglitazone reduced the proliferation and induced apoptosis in synovial cells. Luciferase reporter assay demonstrated that not only PPAR␥ ligands but also NSAIDs, which could induce apoptosis, increased the activation of PPAR␥ in synovial cells. Furthermore, the ability of NSAIDs and PPAR␥ ligands to stimulate the activation of PPAR␥ correlated with their ability to decrease cell viability(r ϭ 0.92, p Ͻ 0.01) and ability to induce DNA fragmentation (r ϭ 0.97, p Ͻ 0.001) in synovial cells. These results suggest that PPAR␥ is an attractive target for induction of apoptosis in rheumatoid synovial cells and that the activation of the PPAR␥ pathway is associated with the apoptotic action of NSAIDs.