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Biomedical subjects

Toshiaki Shimizu

Publications and source records attributed to Toshiaki Shimizu.

At least 19 recordsLinked to original sources
PubMed2007

Effects of iron-unsaturated human lactoferrin on hydrogen peroxide-induced oxidative damage in intestinal epithelial cells.

Human milk (HM) contains various bioactive antioxidants. Lactoferrin (Lf) has been assumed to be one of the major antioxidants in HM. We examined the antioxidative properties of iron-unsaturated human Lf (apo-hLf, the major form of Lf in HM) in two intestinal epithelial cell lines: (1) An intestinal epithelial cell line (IEC-6) were preincubated for 24 h with either 50 microg/mL of apo-hLf, iron-saturated human Lf (holo-hLf), iron-unsaturated bovine transferrin (apo-bTf), or 800 ng/mL of the iron-chelating compound deferoxamine (DFX), followed by hydrogen peroxide (H2O2) challenge to induce oxidative stress. Survival rates were significantly higher in the cells preincubated with apo-hLf and DFX than those preincubated with holo-hLf. (2) Caco-2 cells were preincubated with or without apo-hLf for 24 h, followed by an H2O2 challenge. Intracellular oxidative stress was assessed by a fluorescent probe, 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA). Fluorescent intensity of cell images and cell homogenates was significantly lower in the cells preincubated with apo-hLF than those preincubated without apo-hLF. Our study indicates that apo-hLf alleviates H2O2-induced oxidative damage in intestinal cells due to the iron-chelating capacity. Therefore, Lf in HM may act as an antioxidant in the gastrointestinal tract (GIT).

Animals↗
PubMed2006

A prospective study on the use of mycophenolate mofetil in children with cyclosporine-dependent nephrotic syndrome.

Cyclosporine A (CsA) has relieved children with steroid-dependent nephrotic syndrome (NS) from steroid toxicity. However, most patients frequently relapse again when CsA is withdrawn, resulting in the development of CsA nephropathy for its long-term use. In order to assess the efficacy of mycophenolate mofetil (MMF) therapy, we prospectively analyzed 12 children with idiopathic steroid-dependent NS requiring long-term CsA therapy with MMF for at least 6 months. Mean follow-up after starting MMF was 11 months (range 6-42). The mean MMF dose required was 610+/-95 mg/m(2)/12 h, which maintained mean predose mycophenolic acid (C0-MPA) levels of 2.4+/-1.1 mcg/ml. Treatment with MMF resulted in CsA and/or prednisolone (PSL) sparing, with a reduction in mean CsA dose from 3.5+/-1.3 to 1.5+/-2.4 mg/kg/day (p<0.01), and mean PSL dose from 0.29+/-0.16 to 0.21+/-0.11 mg/kg/day (p<0.05). Nine of 12 patients (75%) were finally able to be weaned off CsA. Mean relapse rates decreased from 2.7+/-1.6 to 0.6+/-0.9 episodes/year (p<0.01). Relapse-free ratio on MMF therapy was lower in patients whose average C0-MPA levels were less than 2 mcg/ml (p<0.05). Our experience demonstrates that MMF therapy results in significant CsA and/or steroid sparing and reduction in relapse rates in children with CsA-dependent NS.

Adolescent↗
PubMed2006

Evaluation of psychosomatic stress in children by measuring salivary chromogranin A.

AIM: To investigate the usefulness of salivary chromogranin A (CgA) and cortisol as stress markers, and the effects of distraction on the suppression of stress in children. METHODS: We examined salivary CgA and cortisol responses before and after venipuncture in hospitalized children with and without distraction using a kaleidoscope. RESULTS: Salivary CgA levels immediately after venipuncture were significantly higher than those immediately before it, and at 60 min after venipuncture they were significantly lower than those immediately after it. However, salivary cortisol showed no significant differences at any of the three time points. In contrast, distracted by the kaleidoscope, there were no significant differences in salivary CgA and cortisol levels at all three time points. CONCLUSION: In children, salivary CgA level is a useful marker of stress. As an index of the effect of distraction, the measurement of salivary CgA is useful.

Adolescent↗
PubMed2006

Comparison of the phospholipid classes in human milk in Japanese mothers of term and preterm infants.

BACKGROUND: Phospholipids (PLs) play an essential role in the growth and brain development of infants. AIM: To investigate PL composition in human milk (HM), including lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidylcholine (PC) and sphingomyelin (SM), from healthy Japanese mothers. Analyses were performed on colostrum, transitional milk and mature milk from mothers of preterm and term infants. METHODS: HM samples were collected from mothers of 15 term infants (term group) and of 19 preterm infants (preterm group). PL composition was determined by two-dimensional thin-layer chromatography in conjunction with phosphorus analysis. RESULTS: In both groups, the PL content (% of total lipid) of mature milk was significantly lower than in colostrum. SM and PC were the main PLs in HM, but in the preterm group, the percentage of SM in mature milk was significantly higher and PC in mature milk was significantly lower than in the term group. CONCLUSION: The transition from colostrum to mature milk leads to an increase in SM and a decrease in PC in the HM of preterm infants, along with a decrease in PL content. This is the first report to demonstrate the differences in PL composition in HM between mothers of preterm and term infants.

Adolescent↗
PubMed2006

Usefulness of nonbreath-hold 1-shot magnetic resonance cholangiopancreatography for the evaluation of choledochal cyst in children.

OBJECTIVE: The aim of this study was to clarify the usefulness of magnetic resonance cholangiopancreatography (MRCP) for the evaluation of choledochal cyst in children. SUBJECTS AND METHODS: MRCP was performed preoperatively in 33 patients. The MRCP findings were compared with those of endoscopic retrograde cholangiopancreatography or intraoperative cholangiopancreatography. RESULTS: In all 33 patients, MRCP could detect choledochal cyst. The detection rate of a cyst in the main pancreatic duct was 62.2%, of abnormal union of the pancreaticobiliary junction (AUPBJ) was 53.3%, of dilatation or abnormalities of the main pancreatic duct was 75.0% and of a protein plug or stone was 76.9%. In patients under 2 years of age (group A), these findings were significantly lower than those of patients above 2 years of age (group B) [main pancreatic duct: 16.6% (1/6) vs 73.1% (19/26), P < 0.01; AUPBJ: 0.0% (0/6) vs 66.7% (16/24), P < 0.05; and protein plug or stone: 0.0% (0/2) vs 90.9% (10/11), P < 0.05]. The detection rate of AUPBJ in the patients with fusiform dilatation was superior to that of those with cystic dilatation [70% (14/20) vs 20% (2/10), P < 0.05]. In the patients with fusiform dilatation, the detection rate in group A was significantly lower than that in group B [0.0% (0/3) vs 82.4% (14/17), P < 0.01]; however, there was no significant difference between the 2 groups in the detection of cystic dilatation. CONCLUSION: In patients older than 2 years, MRCP should be the first-choice method for confirming the diagnosis and for ensuring accurate visualization of the pancreaticobiliary system.

Adolescent↗
PubMed2006

Bifidobacterium breve enhances transforming growth factor beta1 signaling by regulating Smad7 expression in preterm infants.

OBJECTIVES: Transforming growth factor (TGF) beta1 displays a broad spectrum of activities in mucosal regulation, including induction of oral tolerance, potent anti-inflammatory effects, mucosal IgA expression and effects on epithelial cell proliferation and differentiation. The present study examined the effect of probiotics on the immunologic system of preterm infants in relation to TGF-beta signaling. METHODS: Subjects comprised 19 preterm infants divided into 2 groups: receiving Bifidobacterium breve supplementation (B. breve group) and without supplementation (controls). Blood samples were collected from both groups on days 0, 14 and 28 after birth. Serum cytokine levels were measured using enzyme-linked immunosorbent assay, and expression levels of the TGF-beta signaling molecule, Smad, were examined using semiquantitative reverse transcriptase-polymerase chain reaction. RESULTS: Serum TGF-beta1 level was elevated on day 14 and remained elevated on day 28 in the B. breve group. Level of messenger RNA expression was enhanced for Smad3 and reduced for Smad7 (antagonistic Smad) after B. breve administration relative to levels in controls on day 28. CONCLUSIONS: These results demonstrated that the administration of B. breve to preterm infants can up-regulate TGF-beta1 signaling and may possibly be beneficial in attenuating inflammatory and allergic reactions in these infants.

Bifidobacterium↗
PubMed2006

Antimicrobial activities of cinnamyl rifamycin derivatives, T-9 and T-11, against Mycobacterium tuberculosis and Mycobacterium avium complex (MAC) with special reference to the activities against intracellular MAC.

The mycobacterial activities of cinamyl rifamycin derivatives, T-9 and T-11, especially against extracellular and intracellular Mycobacterium avium complex residing within macrophages and type II pneumocytes were compared with those of other rifamycins. The activities of test rifamycins were found to be in the order rifalazil, rifabutin, T-9, T-11, and rifampicin.

Animals↗
PubMed2006

Effects of extremely early enteral feeding on plasma glicentin levels in very-low-birthweight infants.

AIM: Glicentin, an active component of enteroglucagon, is considered to have a significant trophic action on the intestinal mucosa. We examined the effects of extremely early enteral feedings on the postnatal and postprandial changes in plasma glicentin levels in very-low-birthweight (VLBW) infants. METHODS: We measured the plasma glicentin concentrations before and after feedings at 1 or 2 days, 5 or 6 days and 14 days after birth in 21 VLBW infants. The subjects were randomly divided into an extremely early feeding group, which was started on breast milk within 24 h after birth, and a control group, which was started on breast milk more than 24 h after birth. RESULTS: Plasma basal concentrations of glicentin at 5 or 6 days and at 14 days after birth were significantly higher than those at 1 or 2 days after birth in the early feeding group. The basal glicentin level at 14 days after birth was significantly higher than that at 1 or 2 days. The basal levels at 5 or 6 days and at 14 days after birth in the early feeding group were significantly higher than those in the control group. Plasma glicentin concentrations after feeding were significantly higher than those before feeding at 5 or 6 days and 14 days after birth in the early feeding group, but those levels were significantly higher only at 14 days after birth in the control group. CONCLUSION: Our results suggest that extremely early enteral feedings may play an important role in the development of glicentin secretion and intestinal mucosal growth in the early period of life in VLBW infants.

Enteral Nutrition↗
PubMed2006

Disinfection by antiseptics in management of postoperative surgical wounds in urologic operations.

The objective of this study was to confirm that frequent disinfection by antiseptics is unnecessary on surgical wounds of urologic operations. Patients who received urologic operations were divided into 3 groups that had the same surgical dressings but different frequencies of disinfection and different antiseptics used. Surgical wounds were evaluated clinically and bacteriologically for the period until removal of sutures. Of the 97 patients randomly recruited for the study, 3 developed surgical-site infection (SSI). There was no significant difference in the incidence of SSI among the 3 groups. Bacterial counts of surgical wounds increased over time after operation, to similar extents in the 3 groups. The major isolate was Staphylococcus epidermidis, one of the normal florae on the skin. This strain was found at almost equal frequencies in all groups. In conclusion, our study suggested that covering with the surgical dressing without frequent disinfection by antiseptics was effective for prevention of SSI. Thus, traditional frequent disinfection should be abandoned.

Anti-Infective Agents, Local↗
PubMed2005

Thin basement membrane nephropathy associated with minimal change disease in a 15-year-old boy.

Thin basement membrane nephropathy (TBMN) is characterized clinically by persistent hematuria, minimal proteinuria, normal renal function, another family member with hematuria, and a benign course. Especially in childhood TBMN, proteinuria of any degree is reported to be uncommon. We report on a boy with benign familial hematuria found by urinary screening at 3 years of age who presented with nephrotic syndrome (NS) at 15 years of age. His renal histology showed TBMN associated with minimal change disease (MCD). Treatment with corticosteroid resulted in complete remission of NS in a short period of time, while isolated hematuria persisted during the follow-up period despite this therapy. We speculate, therefore, that the nephrotic range proteinuria is not due to TBMN but rather is the manifestation of associated MCD. Several cases of TBMN with NS have been reported in adults, but it has not yet been reported in children in the literature. To our knowledge, this is the first case of childhood TBMN associated with NS resulting from coincidental MCD.

Adolescent↗
PubMed2005

Antimicrobial activity of picolinic acid against extracellular and intracellular Mycobacterium avium complex and its combined activity with clarithromycin, rifampicin and fluoroquinolones.

OBJECTIVES: A natural metal ion chelator, picolinic acid (PA), is known to potentiate macrophage antimycobacterial activity. Here, we studied the antimicrobial activity of PA against extracellular and intramacrophage Mycobacterium avium complex (MAC) organisms. METHODS: MAC organisms, MAC-infected macrophages or MAC-infected type II pneumocytes were cultured in the presence or absence of PA with or without antimycobacterial drugs, and residual bacterial cfu of extracellular or intracellular MAC were counted on 7H11 agar plates. RESULTS: First, PA exhibited antimicrobial activity against extracellular and intramacrophage MAC. The effect of PA was mimicked by other metal ion-chelating agents, such as ethylenediamine tetraacetic acid and O,O'-bis (2-aminophenyl) ethyleneglycol-N,N,N',N'-tetraacetic acid. Second, PA potentiated antimicrobial effects of a two-drug combination of clarithromycin/rifampicin and some fluoroquinolones (levofloxacin, sitafloxacin and gatifloxacin) against extracellular and intramacrophage MAC. Similar combined effects of PA with clarithromycin/rifampicin were also seen in the case of MAC residing within type II alveolar epithelial cells. CONCLUSIONS: PA exerted an appreciable anti-MAC activity, when used singly or in combination with some antimycobacterial drugs (clarithromycin/rifampicin and fluoroquinolones), suggesting the usefulness of PA as an adjunct for clinical antimicrobial chemotherapy of MAC infections.

Animals↗
PubMed2005

Combined effects of ATP on the therapeutic efficacy of antimicrobial drug regimens against Mycobacterium avium complex infection in mice and roles of cytosolic phospholipase A2-dependent mechanisms in the ATP-mediated potentiation of antimycobacterial host resistance.

ATP, which serves as a mediator of intramacrophage signaling pathways through purinoceptors, is known to potentiate macrophage antimycobacterial activity. In this study we examined the effects of ATP in potentiating host resistance to Mycobacterium avium complex (MAC) infection in mice undergoing treatment with a drug regimen using clarithromycin and rifamycin and obtained the following findings. First, the administration of ATP in combination with the clarithromycin and rifamycin regimen accelerated bacterial elimination in MAC-infected mice without causing changes in the histopathological features or the mRNA expression of pro- or anti-inflammatory cytokines from those in the mice not given ATP. Second, ATP potentiated the anti-MAC bactericidal activity of macrophages cultivated in the presence of clarithromycin and rifamycin. This effect of ATP was closely related to intracellular Ca2+ mobilization and was specifically blocked by a cytosolic phospholipase A2 (cPLA2) inhibitor, arachidonyl trifluoromethylketone. Third, intramacrophage translocation of membranous arachidonic acid molecules to MAC-containing phagosomes was also specifically blocked by arachidonyl trifluoromethylketone. In the confocal microscopic observation of MAC-infected macrophages, ATP enhanced the intracellular translocation of cPLA2 into MAC-containing phagosomes. These findings suggest that ATP increases the host anti-MAC resistance by potentiating the antimycobacterial activity of host macrophages and that the cPLA2-dependent generation of arachidonic acid from the phagosomal membrane is essential for such a phenomenon.

Adenosine Triphosphate↗
PubMed2005

High-dose mizoribine therapy for childhood-onset frequently relapsing steroid-dependent nephrotic syndrome with cyclosporin nephrotoxicity.

Cyclosporin A (CsA) is an effective treatment for frequently relapsing steroid-dependent nephrotic syndrome (FR-SDNS), but its use can be complicated by renal toxicity and a high incidence of relapses after withdrawal. We report 9 adolescent patients with childhood-onset FR-SDNS who had been treated with long-term CsA that resulted in moderate-to-severe CsA nephropathy (CsAN). They were treated with high-dose (mean: 10.1 mg/kg per day) mizoribine (MZR) in an attempt to allow weaning of CsA and/or steroid therapy, and reduce the frequency of relapses. Seven out of 9 patients were weaned off CsA by 1-year follow-up, although in the remaining 2 patients, MZR did not show any beneficial effects. Overall, this high-dose MZR therapy results in significant steroid sparing and reduction in relapse rates in our patients. Our experience shows that high-dose MZR therapy in patients with FR-SDNS who are also CsA-dependent appears to be effective in reducing CsA exposure as well as in decreasing the frequency of relapses.

Adolescent↗