Mariko Wada

Effects of the enteral administration of Bifidobacterium breve on patients undergoing chemotherapy for pediatric malignancies

PurposeProbiotics are expected to be effective in prophylaxis of infection in cancer patient, since infections in neutropenics are mainly caused by endogenous flora through the intestinal mucosa. However, the experience with the use of probiotics in immunocompromised patients is limited, and precise fecal bacteria analysis has not been reported. The aim of the study was to evaluate the effects of the enteral administration of the probiotic, Bifidobacterium breve strain Yakult, on its ability to prevent infection, fecal micro flora, and intestinal environments in cancer patients on chemotherapy.MethodsA placebo-controlled trial was performed at Juntendo University Hospital. Patients with malignancies admitted for chemotherapy (n = 42) were randomized into two groups receiving probiotic or placebo. The effects on infectious complications, natural killer cells, fecal micro flora, fecal organic acid concentrations, and fecal pH were studied.ResultsThe frequency of fever and the use of intravenous antibiotics were lower in the probiotic group than the placebo group. The probiotic administration enhanced the habitation of anaerobes. Disruption of the intestinal microbiota after chemotherapy such as the increase in the population levels of Enterobacteriaceae was observed at more pronounced manner in the placebo group in comparison to the probiotic group. The concentrations of total organic acids were maintained most of the time at the normal level, which constantly maintained the pH below 7.0 only in the probiotic group.ConclusionThese data, although based on a limited number of patients and samples, suggest that administration of B. breve strain Yakult could be an effective approach for achieving clinical benefits in immunocompromised hosts by improving their intestinal environments.

Well-controlled proinflammatory cytokine responses of Peyer’s patch cells to probiotic Lactobacillus casei

In order to clarify the probiotic features of immunomodulation, cytokine production by murine spleen and Peyer’s patch (PP) cells was examined in response to probiotic and pathogenic bacteria. In spleen cells, probiotic Lactobacillus casei induced interleukin (IL)‐12 production by CD11b+ cells more strongly than pathogenic Gram‐positive and Gram‐negative bacteria and effectively promoted the development of T helper (Th) type 1 cells followed by high levels of secretion of interferon (IFN)‐γ. Although the levels of IL‐12 secreted by PP cells in response to L. casei were lower in comparison with spleen cells, Th1 cells developed as a result of this low‐level induction of IL‐12. However, IFN‐γ secretion by the L. casei‐induced Th1 cells stimulated with a specific antigen was down‐regulated in PP cells. Development of IL‐17‐producing Th17 cells was efficiently induced in PP cells by antigen stimulation. Lactobacillus casei slightly, but significantly, inhibited the antigen‐induced secretion of IL‐17 without a decrease in the proportion of Th17 cells. No bacteria tested induced the development of IL‐10‐producing, transforming growth factor‐β‐producing or Foxp3‐expressing regulatory T cells, thus suggesting that certain probiotics might regulate proinflammatory responses through as yet unidentified mechanisms in PP cells. These data show probiotic L. casei to have considerable potential to induce IL‐12 production and promote Th1 cell development, but the secretion of proinflammatory cytokines such as IL‐12 and IL‐17 may be well controlled in PP cells.

Neonatal transient eosinophilic colitis causes lower gastrointestinal bleeding in early infancy.

Background: Lower gastrointestinal bleeding (LGB), particularly in newborns, is of serious concern and requires urgent investigation and hospital care. Whereas allergic proctocolitis caused by food protein is a significant cause of LGB in infants with eosinophilia, there are several cases of diseases with symptoms similar to those of allergic proctocolitis but without an apparent allergic reaction influence. Patients and Methods: We examined 2 neonates using rectosigmoidoscopy who showed eosinophilia and experienced fresh LGB soon after birth and before their first feedings. Serum eosinic cationic protein (ECP) and platelet activating factor (PAF) levels were also examined in the second case to confirm the involvement of eosinophils for its pathogenesis. Results: Both patients were in a clinically stable condition, and their abdomens were soft. The results of their blood analyses, abdominal radiographs, and stool cultures were normal, but they had gross eosinophilia: the eosinophil counts were 9014/mm3 (patient 1) and 1955/mm3 (patient 2). Rectosigmoidoscopy with colonic mucosal biopsy revealed nodular lymphoid hyperplasia with a pale mucosal surface and massive oozing with diffuse eosinophilic infiltration in the lamina propria. In patient 2 the serum ECP and PAF levels were elevated to 123 μg/L (normal, <14.7) and 13.1 μmol/L/min (normal, <6). A few days after intravenous hydration therapy, LGB was no longer detected, and the serum ECP and PAF levels returned to normal. Conclusions: Inasmuch as these infants had LGB similar to allergic proctocolitis without any allergic reactions, we suggest that infiltrated eosinophils in the colonic mucosa could be involved in the pathogenesis of LGB in early infancy.

Quantitative reverse transcription-PCR assay for the rapid detection of methicillin-resistant Staphylococcus aureus

Aim:  To evaluate a new quantitative reverse transcription‐PCR (qRT‐PCR) assay for the rapid detection of methicillin‐resistant Staphylococcus aureus (MRSA).

Peroxisome proliferator-activated receptor γ 2 mutation may cause a subset of ulcerative colitis

Aim:  Previous studies suggest the homeostasis between acquisition of tolerance to the indigenous microflora and protective immune responses appears to be disrupted in inflammatory bowel disease (IBD). Some experimental studies indicate peroxisome proliferator‐activated receptor γ (PPARγ) has been implicated as a regulator of intestinal inflammatory responses. In addition, the toll‐like receptor (TLR)‐4 can regulate expression of PPARγ in colonic epithelial cells. We attempted to demonstrate whether the functional imbalance between TLRs and PPARγ could lead to the onset and some polymorphisms of those genes could contribute to susceptibility to IBD.

Anti-infectious activity of synbiotics in a novel mouse model of methicillin-resistant Staphylococcus aureus infection.

The anti‐infectious activity of synbiotics against methicillin‐resistant Staphylococcus aureus (MRSA) infection was evaluated using a novel lethal mouse model. Groups of 12 mice treated with multiple antibiotics were infected orally with a clinical isolate of MRSA at an inoculum of 108 CFU on day 7 after starting the antibiotics. A dose of 400 mg/kg 5‐fluorouracil (5‐FU) was injected intraperitoneally on day 7 after the infection. A dose of 108 CFU Bifidobacterium breve strain Yakult and 10 mg of galactooligosaccharides (GOS) were given orally to mice daily with the antibiotic treatment until day 28. The intestinal population levels of MRSA in the mice on multiple antibiotics were maintained stably at 108 CFU/g of intestinal contents after oral MRSA infection and the subsequent 5‐FU treatment killed all the mice in the group within 14 days. B. breve administration saved most of the mice, but the synbiotic treatment saved all of the mice from lethal MRSA infection. The synbiotic treatment was effective for the treatment of intestinal infection caused by four MRSA strains with different toxin productions. There was a large difference among the six Bifidobacteria strains that were naturally resistant to the antibacterial drugs used. B. breve in combination with GOS is demonstrated to have valuable preventive and curative effects against even fatal MRSA infections.

Effect of Suplatast Tosilate on Antileukotriene Non-Responders with Mild-to-Moderate Persistent Asthma

BACKGROUND Immunomodulatory therapy has been recently introduced for the management of asthma. Suplatast tosilate (ST), a new immune-modifying drug, is known to improve the airway function by inhibiting the release of Th-2 cytokines. However, its efficacy as a controller listed in the guideline, Global Initiative for Asthma 2005 has not been established. In this study we investigated the role of ST in leukotriene receptor antagonist (LTRA) non-responders with mild-to-moderate persistent asthma before initiating corticosteroids inhalation therapy. METHODS This was a prospective open-level clinical trial. LTRAs was given to 41 patients with asthma for 4 weeks and clinical efficacy was assessed using daily symptom scores. The 10 patients, aged 2.5-8.5 years, who failed to show clinical improvement, were defined as LTRA non-responders. After a 1-week washout period, the efficacy of ST was investigated and compared with LTRA non-responders for the following 4 weeks. RESULTS LTRA non-responders showed a significant improvement in the average symptom score, peak expiratory flow, use of rescue medication and the proportion of symptom-free days with ST therapy. CONCLUSIONS ST is a good choice for patients who have failed to respond to LTRAs. ST should therefore be added to the list of treatment options for such patients.

Pulse steroids as induction therapy for children with ulcerative colitis.

Background:  Corticosteroids therapy, classically the first‐line treatment for ulcerative colitis (UC), often causes serious side‐effects. Theoretically, pulse steroid therapy where high doses are given for a shorter period may have maximal beneficial effects and minimal side‐effects as induction therapy for UC. We have therefore retrospectively compared induction therapy using pulse steroids with conventional steroid treatment for children and adolescents with moderate‐to‐severe UC.