Growth of bulk ß-Ga2O3 crystals from melt without precious-metal crucible by pulling from a cold container.

We report the growth of bulk ß-Ga2O3 crystals based on crystal pulling from a melt using a cold container without employing a precious-metal crucible. Our approach, named oxide crystal growth from cold crucible (OCCC), is a fusion between the skull-melting and Czochralski methods. The absence of an expensive precious-metal crucible makes this a cost-effective crystal growth method, which is a critical factor in the semiconductor industry. An original construction 0.4-0.5 MHz SiC MOSFET transistor generator with power up to 35 kW was used to successfully grow bulk ß-Ga2O3 crystals with diameters up to 46 mm. Also, an original diameter control system by generator frequency change was applied. In this preliminary study, the full width at half maximum of the X-ray rocking curve from the obtained ß-Ga2O3 crystals with diameters ≤ 46 mm was comparable to those of ß-Ga2O3 produced by edge-defined film fed growth. Moreover, as expected, the purity of the obtained crystals was high because only raw material-derived impurities were detected, and contamination from the process, such as insulation and noble metals, was below the detection limit. Our results indicate that the OCCC technique can be used to produce high-purity bulk ß-Ga2O3 single crystalline substrate.

Effectiveness of patient and staff cohorting to reduce the risk of vancomycin-resistant enterococcus (VRE) acquisition: a retrospective cohort study during a VRE outbreak in Japan.

BACKGROUND: Patient and staff cohorting is part of a bundle approach in the response to multi-drug-resistant organisms, but its effectiveness is not fully clarified. This study compared the risks of acquiring vancomycin-resistant Enterococcus faecium (VREfm) at a hospital during a VREfm outbreak based on contact characteristics in order to better understand the effectiveness of cohorting. METHODS: Exposure came from contact with patients with VREfm (infectors), including existing patients with VREfm and patients who acquired VREfm during the study period. Contact was defined as length of contact time, degree of sharing space, and care by the same nurses as those caring for infectors between January and March 2018. The outcome was VREfm acquisition as determined through monthly stool or rectal screening cultures. Incidence rates were calculated based on contact patterns, and incidence rate ratios (IRRs) were compared. FINDINGS: Among 272 inpatients (4038 patient-days), 43 patients acquired VREfm with the same or similar pulsotype. Incidence rates were 8.45 per 1000 patient-days when susceptible inpatients were on the same ward as an infector but cared for by different nurses (reference), 16.96 when susceptible inpatients were on the same ward as an infector and cared for by the same nurses [IRR 2.01, 95% confidence interval (CI) 0.62-10.28], and 52.91 when susceptible inpatients shared a room with an infector (IRR 6.26, 95% CI 1.61-35.40). CONCLUSION: Compared with susceptible inpatients in a different room from infectors and not being cared for by the same nurses, the risk of VREfm acquisition could be six times higher for susceptible inpatients who are in the same room as infectors, and could be double for susceptible inpatients cared for by the same nurses as infectors.

Interferon-γ-producing B cells induce the formation of gastric lymphoid follicles after Helicobacter suis infection.

Helicobacter (H.) suis is capable of infecting various animals including humans, and H. suis infections can lead to gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Recently, we reported that interferon-γ (IFN-γ) was highly expressed in the stomachs of H. suis-infected mice, but the direct relationship between the upregulation of IFN-γ expression and the formation of gastric lymphoid follicles after H. suis infection remains unclear. Here, we demonstrated that the IFN-γ produced by B cells plays an important role in the formation of gastric lymphoid follicles after H. suis infection. In addition, IFN-γ-producing B cells evoked gastric lymphoid follicle formation independent of T-cell help, suggesting that they are crucial for the development of gastric MALT induced by Helicobacter infection.

JTT-130, a novel intestine-specific inhibitor of microsomal triglyceride transfer protein, ameliorates impaired glucose and lipid metabolism in Zucker diabetic fatty rats.

AIM: Microsomal triglyceride transfer protein (MTP) takes part in the mobilization of triglyceride-rich lipoproteins from enterocytes and hepatocytes. We investigated the effects of JTT-130, a novel intestine-specific MTP inhibitor, on impaired glucose and lipid metabolism in Zucker diabetic fatty (ZDF) rats. METHODS: Male ZDF rats were fed a regular powdered diet with or without JTT-130 as a food admixture (0.01-0.02%) for 6 weeks. Food intake, body weight, blood biochemical parameters, fecal lipid contents, hepatic lipid contents, tissue mRNA levels and glucose utilization in adipose tissues were assessed. An intraperitoneal glucose tolerance test (IPGTT) and histological analysis of the pancreas were performed. RESULTS: JTT-130 treatment decreased food intake, glycated hemoglobin, plasma levels of glucose, triglycerides and total cholesterol, hepatic levels of triglycerides and cholesterol and hepatic mRNA levels of glucose-6-phosphatase, phosphoenolpyruvate carboxykinase and fructose-1,6-bisphosphatase. JTT-130 treatment increased fecal levels of free fatty acids and cholesterol, plasma levels of glucagon-like peptide-1 and peptide YY, mRNA levels of glucose transporter 4 (GLUT4) and lipoprotein lipase in adipose tissues and GLUT4 in muscle and glucose utilization in adipose tissues. Plasma insulin decreased after 2 weeks and increased after 4 weeks of JTT-130 treatment. Plasma glucose in the JTT-130-treated rats was lower with higher plasma insulin than in the control rats during the IPGTT. The islets of the JTT-130-treated rats were larger and contained more insulin than those of the control rats. CONCLUSIONS: JTT-130 ameliorates impaired glucose and lipid metabolism in the ZDF rats thereby suggesting that JTT-130 could be useful for prevention and treatment of type 2 diabetes.

An Evaluation of a Refresher Training Intervention for HIV Lay Counsellors in Chongwe District; Zambia

To address a severe shortage of human resources for health; the Zambian Ministry of Health has begun to make use of lay counsellors for HIV counselling and testing. However; their skills and knowledge rarely have been reviewed or refreshed. We conducted a two-day refresher workshop for lay counsellors to review their performance and refresh their skills and knowledge. The objective of this study was to evaluate the refresher training intervention for HIV lay counsellors in the rural district of Chongwe in Zambia. The two-day refreshertraining workshop was held in November 2009. Twenty-five lay counsellors were selected by District Health Office and participated in the workshop. The workshop included: the opening; a pre-training exercise; lectures on quality assurance with regard to testing and safety precautions; lectures on counselling; filling the gap/QetA session; and a post-training exercise. In both the pre- and post-trainingexercise; participants answered 25 true/false questions and tested 10 blood panel samples to demonstrate their knowledge and skill on HIV counselling and testing. The average overall knowledge test score increased from 79 to 95 (p0.001). At the baseline; knowledge test scores in topic of standard precaution and post-exposure prophylaxis were relatively low (58) but rose to 95 after the training (p0.001). The per cent agreement of HIV testing by lay counsellors with reference laboratory was 99.2. Participants' knowledge was improved during the workshop and skill at HIV testing was found to remain at a high level of accuracy. Relatively weak knowledge of standard precautions and post-exposure prophylaxis suggests that lay counsellors are at risk of nosocomial infections; particularly in the absence of refresher training interventions. We conclude that the refresher training was effective for improving the knowledge and skills of lay counsellors and provided an opportunity to monitor their performance

Prevention by lansoprazole, a proton pump inhibitor, of indomethacin -induced small intestinal ulceration in rats through induction of heme oxygenase-1.

The effect of lansoprazole, a proton pump inhibitor (PPI), on indomethacin-induced small intestinal ulceration was examined in rats, particularly in relation to heme oxygenase (HO)-1. The animals were administered indomethacin (10 mg/kg, p.o.) and killed 24 h later. Lansoprazole (30-100 mg/kg, p.o.) and omeprazole (30-100 mg/kg, p.o.) were given 30 min before the administration of indomethacin, while tin-protoporphyrin IX (SnPP: 30 mg/kg, i.v.), an inhibitor of HO-1, was injected 10 min before indomethacin or lansoprazole. Indomethacin produced hemorrhagic lesions in the small intestine, accompanied with an increase of mucosal invasion of enterobacteria, inducible nitric oxide synthase (iNOS) expression, and myeloperoxidase (MPO) activity in the mucosa. Pretreatment with lansoprazole dose- dependently reduced the severity of the indomethacin-induced intestinal lesions, with suppression of the increased MPO activity, while omeprazole had no effect. Pretreatment with SnPP significantly exacerbated these intestinal lesions and almost totally abolished the protective effect of lansoprazole. The up-regulation of iNOS mRNA expression following indomethacin was suppressed by lansoprazole in a SnPP-inhibitable manner, although the enhanced enterobacterial invasion remained unaffected. The amount of HO-1 protein in the intestinal mucosa was significantly increased by lansoprazole but not by omeprazole. Prior administration of carbon monoxide (CO)-releasing molecule-2 (CORM-2; 10 mg/kg, i.p.) significantly reduced the severity of these lesions and the enhancement of mucosal iNOS mRNA expression induced in the small intestine by indomethacin. These results suggest that lansoprazole prevents indomethacin-induced small intestinal ulceration, and this effect is associated with inhibition of iNOS expression, through up-regulation of HO-1/CO production in the mucosa.

Cot/Tpl2 regulates IL-23 p19 expression in LPS-stimulated macrophages through ERK activation.

We have previously reported that a serine/threonine protein kinase, Cot/Tpl2, is a negative regulator of Th1-type immunity through inhibiting IL-12 expression in antigen presenting cells (APCs) stimulated by Toll-like receptor (TLR) ligands. We here show that Cot/Tpl2(-/-) macrophages produce significantly less IL-23, an important regulator of Th17-type response, than the wild-type counterparts in response to lipopolysaccharide (LPS), which is a ligand for TLR4. The decreased IL-23 production in Cot/Tpl2(-/-) macrophages is, at least partly, regulated at the transcriptional level, as the LPS-mediated IL-23 p19 mRNA induction was significantly less in Cot/Tpl2(-/-) macrophages. Chemical inhibition of extracellular signal-regulated kinase (ERK) activity similarly inhibited IL-23 expression in LPS-stimulated wild-type macrophages. As Cot/Tpl2 is an essential upstream component of the ERK activation pathway of LPS, it is suggested that Cot/Tpl2 positively regulates IL-23 expression through ERK activation. These results indicate that Cot/Tpl2 may be involved in balancing Th1/Th17 differentiation by regulating the expression ratio of IL-12 and IL-23 in APCs.

Cot/Tpl2 regulates IL-23 p19 expression in LPS-stimulated macrophages through ERK activation

No disponible

We have previously reported that a serine/threonine protein kinase, Cot/Tpl2, is a negative regulatorof Th1-type immunity through inhibiting IL-12 expression in antigen presenting cells (APCs)stimulated by Toll-like receptor (TLR) ligands. We here show that Cot/Tpl2-/- macrophages produce significantly less IL-23, an important regulator of Th17-type response, than the wild-type counterparts in response to lipopolysaccharide (LPS), which is a ligand for TLR4. The decreased IL-23 production in Cot/Tpl2-/- macrophages is, at least partly, regulated at the transcriptional level, as the LPS-mediated IL-23 p19 mRNA induction was significantly less in Cot/Tpl2-/- macrophages. Chemical inhibition of extracellular signal-regulated kinase (ERK) activity similarly inhibited IL-23 expression inLPS-stimulated wild-type macrophages. As Cot/Tpl2 is an essential upstream component of theERK activation pathway of LPS, it is suggested that Cot/Tpl2 positively regulates IL-23 expression through ERK activation. These results indicate that Cot/Tpl2 may be involved in balancing Th1/Th17 differentiation by regulating the expression ratio of IL-12 and IL-23 in APCs (AU)

Involvement of Cot/Tp12 in bone loss during periodontitis.

Periodontitis causes resorption of alveolar bone, in which RANKL induces osteoclastogenesis. The binding of lipopolysaccharide to Toll-like receptors causes phosphorylation of Cot/Tp12 to activate the MAPK cascade. Previous in vitro studies showed that Cot/Tp12 was essential for the induction of RANKL expression by lipopolysaccharide. In this study, we examined whether Cot/Tp12 deficiency reduced the progression of alveolar bone loss and osteoclastogenesis during experimental periodontitis. We found that the extent of alveolar bone loss and osteoclastogenesis induced by ligature-induced periodontitis was decreased in Cot/Tp12-deficient mice. In addition, reduction of RANKL expression was observed in periodontal tissues of Cot/Tp12-deficient mice with experimental periodontitis. Furthermore, we found that Cot/Tp12 was involved in the induction of TNF-alpha mRNA expression in gingiva of mice with experimental periodontitis. Our observations suggested that Cot/Tp12 is essential for the progression of alveolar bone loss and osteoclastogenesis in periodontal tissue during experimental periodontitis mediated through increased RANKL expression.

Oxidative stress causes alveolar bone loss in metabolic syndrome model mice with type 2 diabetes.

BACKGROUND AND OBJECTIVE: Alveolar bone loss is caused by a host response to periodontal pathogens, and its progression is often enhanced by systemic conditions such as insulin resistance. Alveolar bone dehiscence has been observed in KK-A(y) mice, which are metabolic syndrome model mice with type 2 diabetes. The aim of this study was to investigate inducements responsible for alveolar bone dehiscence in the KK-A(y) mice. MATERIAL AND METHODS: The expression of endothelial nitric oxide synthase in the mandibles of mice was detected using immunohistochemical staining and the reverse transcription-polymerase chain reaction. After administration of N-acetylcysteine, an antioxidant, to KK-A(y) mice, alveolar bone loss and the expression of endothelial nitric oxide synthase protein in gingival keratinocytes and of hydrogen peroxide concentrations in plasma, were analyzed. The effect of hydrogen peroxide on endothelial nitric oxide synthase expression in keratinocytes was examined using cultured keratinocytes. RESULTS: The expression of endothelial nitric oxide synthase was decreased in gingival keratinocytes from KK-A(y) mice compared with gingival keratinocytes from control mice. Administration of N-acetylcysteine to the mice restored endothelial nitric oxide synthase expression in the gingival keratinocytes, suppressed the alveolar bone loss and decreased the hydrogen peroxide concentrations in plasma without the improvement of obesity or diabetes. In vitro, stimulation with hydrogen peroxide decreased the expression level of endothelial nitric oxide synthase in cultured keratinocytes, which was restored by the addition of N-acetylcysteine. CONCLUSION: Reactive oxygen species, such as hydrogen peroxide, are responsible for the alveolar bone loss accompanied by decreased endothelial nitric oxide synthase expression in KK-A(y) mice. Therefore, we propose a working hypothesis that the generation of oxidative stress is an underlying systemic condition that enhances alveolar bone loss in periodontitis occurring as a complication of diabetes.

Force-induced IL-8 from periodontal ligament cells requires IL-1beta.

During orthodontic tooth movement, mechanical stresses induce inflammatory reactions in the periodontal ligament (PDL). We hypothesized that chemokines released from PDL cells under mechanical stress regulate osteoclastogenesis, and investigated the profiles and mechanisms of chemokine expression by human PDL cells in response to mechanical stress. In vitro, shear stress and pressure force rapidly increased the gene and protein expressions of IL-8/CXCL8 by PDL cells. Consistently, amounts of IL-8 in the gingival crevicular fluid of healthy individuals increased within 2 to 4 days of orthodontic force application. The PDL cells constitutively expressed low levels of IL-1beta, which were not further increased by mechanical stress. Interestingly, neutralization of IL-1beta abolished IL-8 induction by mechanical stresses, indicating that IL-1beta is essential for IL-8 induction, presumably though autocrine or paracrine mechanisms. Finally, experiments with signal-specific inhibitors indicated that MAP kinase activation is essential for IL-8 induction.

Influence of the involvement of partners in the mother class with voluntary confidential counselling and testing acceptance for prevention of mother to child transmission of HIV programme (PMTCT programme) in Cambodia.

The National Maternal and Child Health Center in Phnom Penh, Cambodia commenced PMTCT services as the first site of the National PMTCT programme of Cambodia in November 2001. However, the acceptance of voluntary confidential counselling and testing (VCCT) in the PMTCT services was not as high as expected. The aim of this study was to evaluate influence of partner participation in the mother class to the PMTCT services. During the first visit to antenatal care, all women were invited to the class, where information on PMTCT was provided. From July 2002, when partner participation started, to May 2005, the acceptance rate to the pre-test counselling of those who attended the class alone was 18.7% (3,234/17,340), while that of the attendees with their partner was 85.1% (2,908/3,417) (p <0.001). All of the couples accepted couple counselling and disclosure of their results to their partners. In conclusion, a strong association was observed between acceptance and partner involvement. However, we should consider also other strategies for future programme improvement.

Long-term follow up study of vertical HTLV-I infection in children breast-fed by seropositive mothers.

Infection of Human T-lymphotropic virus type-I (HTLV-I) was investigated by long-term follow up surveys of mother's milk-fed infants. HTLV-I infections of infants via seropositive mother's milk, that is, anti-HTLV-I antibody-positive infants, increased in number up to the age 2, but no infants became antibody-positive thereafter. Infants who had became antibody positive by age 2 remained so at age 11-12. HTLV-I infection via feeding with mother's milk was established by the age 2. While in epidemiologic surveys an increase of the anti-HTLV-I antibody-positive rate has been reported, this survey revealed that after acquisition of HTLV-I from breast feeding, there was no further horizontal transmission prior to puberty.

Increased hepatocyte growth factor level in cerebrospinal fluid in Alzheimer's disease.

BACKGROUND & OBJECTIVE: Hepatocyte growth factor (HGF), also known as the scatter factor, is a potent mitogen for mature hepatocytes, and also has multifunctional effects on some cells in various organs. Recently, we have found expression and localization of HGF in white matter astrocytes in human brain tissues. Furthermore, immunohistochemistry using anti-HGF antibody revealed more intense immunolabeling in Alzheimer's disease (AD) than control brains. The aim of the study is to investigate the level of HGF in cerebrospinal fluid (CSF) from patients with AD. MATERIAL AND METHODS: We examined the level of HGF in CSF from 34 AD and 15 age-matched disease control patients by highly sensitive enzyme-linked immunoabsorbent assay (ELISA) system. RESULTS: Consistent with the immunohistochemical data, a significantly higher concentration of HGF in AD CSF was found as compared with controls. A significant correlation was also seen between CSF HGF levels and white matter high-signal foci determined on brain magnetic resonance imaging (MRI) in AD patients. CONCLUSION: These results indicate that CSF HGF levels correspond with the white matter damage in AD brain.

Long-term follow-up study of HTLV-I infection in bottle-fed children born to seropositive mothers.

Human T-lymphotropic virus Type-I (HTLV-I) infects children via mother's milk. Infection of Human T-lymphotropic virus Type-I (HTLV-I) was investigated by long-term follow-up surveys of modified milk-fed children. Our observations of modified milk-fed infants revealed that: 1 of 154 (0.6%) at year 1, 5 of 129 (3.9%) at 1.5 years, and 5 of 108 (4.6%) at year 2 were anti-HTLV-I antibody-positive. No infants or children became newly antibody-positive thereafter. Modified milk feeding could prevent the HTLV-I infection of infants from mothers in many cases, however the infants who had became anti-HTLV-I antibody-positive due to established infection by the age 2 remained positive at age 11-12 with persistent infections. Modified milk-fed infants who had been born from HTLV-I seropositive mothers did not show that they had complete protection from HTLV-I infection, but a low infection rate was seen, showing that modified milk feeding is useful to protect from HTLV-I infection.

Hepatocyte growth factor in gingival crevicular fluid and the distribution of hepatocyte growth factor-activator in gingival tissue from adult periodontitis.

Hepatocyte growth factor (HGF), also known as scatter factor, is a broad-spectrum and multifunctional cytokine required for the development, growth and regeneration of various organs and tissues. The expression of HGF in human gingival fibroblasts is induced by inflammatory cytokines such as interleukin 1. Thus, although it is possible that content of HGF in gingival crevicular fluid (GCF) in periodontitis is increased, this has not so far been reported because the volume of GCF is too small to determine HGF by the available enzyme-linked immunosorbent assay (ELISA). A recently developed, highly sensitive ELISA for HGF, with a detection limit of 1 pg/ml sample, has now enabled HGF to be measured in GCF.The mean HGF content in GCF from sites with clinically healthy gingiva, defined by the absence of overt signs of gingival inflammation and a probing depth (PD) <3 mm, was 1.7 ng/ml, and that of periodontitis, defined by obvious alveolar bone loss detected by radiographic examination and a PD> or =3 mm, was 3.23 ng/ml. Although treating the periodontitis did not significantly decrease the HGF concentration despite significantly improved clinical scores such as PD and Gingival Index, the total amount of HGF in GCF did decrease significantly after treatment. HGF was expressed by gingival fibroblasts and inflammatory cells as determined by in situ hybridization. HGF-activator (HGFA), which converts inactive pro-HGF to active mature HGF, was detected in gingival epithelial cells by immunostaining. The expression of HGFA was also confirmed in gingival tissue by reverse transcription-polymerase chain reaction (RT-PCR). These findings indicate that HGF is synthesized and activated in gingiva that is clinically healthy or associated with periodontitis.

Hepatocyte growth factor in cerebrospinal fluid in neurologic disease.

OBJECTIVE: To investigate hepatocyte growth factor (HGF) concentration in cerebrospinal fluid (CSF) in neurologic disease. MATERIALS AND METHODS: We determined CSF concentration of HGF with human-HGF-specific enzyme-linked immunosorbent assays (ELISA) in 121 patients: Alzheimer's disease (AD) (33), amyotrophic lateral sclerosis (ALS) (10), Parkinson's disease (PD) (5), progressive supranuclear palsy (PSP) (3), spinocerebellar degeneration (7), acute disseminating encephalomyelitis (ADEM) (6), human T-lymphotropic virus-1 (HTLV-1)-associated myelopathy (HAM) (6), multiple sclerosis (MS) (7), aseptic meningitis (AM) (12), and peripheral neuropathy and myopathy as control diseases (32). RESULTS: HGF concentrations in CSF were significantly higher with diseases of the central nervous system (CNS) than control diseases and were slightly higher with AD than other neurodegenerative diseases. Values were highest with ADEM but decreased during corticosteroid treatment. We found no relationship between HGF in CSF and CSF cells or protein, immunoglobulin index, or Q albumin. CONCLUSION: It is suggested that high concentrations of HGF in CSF may be partially related to CNS pathology, especially to demyelinating disease.

Comparison of fibronectin content in urinary macromolecules between normal subjects and recurrent stone formers.

OBJECTIVES: Fibronectin (FN: 230 kD) is a multifunctional alpha(2)-glycoprotein distributed throughout the extracellular matrix and body fluids. Recent studies have shown that a variety of molecules, including FN, inhibit the endocytosis of calcium oxalate (CaOx) crystals in vitro. We recently reported that FN was oversecreted from the renal tubular cells as a result of the stimulation of CaOx crystals, and inhibited the aggregation of CaOx crystals and the adhesion of CaOx crystals to the renal tubular cells. In the present study, we investigated the difference of FN content in urinary macromolecules (UMMs) between normal subjects and recurrent stone formers. MATERIALS AND METHODS: Urinary parameters in relation to urolithiasis of normal subjects and recurrent stone formers were measured. Proteins in extracted UMMs from urine of normal subjects and recurrent stone formers were measured with a BioRad protein assay, GAGs in each UMMs with a modified DMB assay and the FN content with the ELISA method. RESULTS: In urinary parameters, citrate was significantly higher in urine from normal subjects (female) than normal subjects (male) or recurrent stone formers, and the other parameters showed no differences between each group. The protein concentrations in UMMs showed no differences between each group. Normal subjects (male and female) showed a significantly higher concentration of GAGs than recurrent stone formers (with and without silent stone). Compared with normal subjects and recurrent stone formers without silent stones, higher FN levels were found in recurrent stone formers with silent stones. Normal subjects showed a significantly higher concentration of FN than recurrent stone formers without silent stones. No difference in FN level was shown between normal subjects (male) and normal subjects (female). CONCLUSION: Recurrent stone formers with silent stones showed a significantly higher concentration of FN in UMMs than normal subjects. This finding suggests that FN might be oversecreted from the renal tubular cells as a result of the stimulation of CaOx stones in vivo. Recurrent stone formers without silent stones showed a significantly lower concentration of FN in UMMs than normal subjects. From this finding it is suggested that FN might play a role as a potent inhibitor of CaOx urolithiasis in a clinical setting.

Strong inhibition of crystal-cell attachment by pediatric urinary macromolecules: a close relationship with high urinary citrate secretion.

OBJECTIVES: To investigate other reasons for the low incidence of pediatric urolithiasis, we evaluated the difference in the crystal-cell adhesion inhibitory activity of urinary macromolecules (UMMs) between children and adults. We also evaluated whether citrates influence the above inhibitory activity, because citrates are important in pediatric urine. METHODS: Urine samples were collected from children and healthy male adults during a 24-hour period, and urinary components with a molecular weight of 3 kDa or greater were extracted as UMMs to compare their inhibitory activity during the adhesion of calcium oxalate monohydrate crystals to cultured Madin-Darby canine kidney cells between children and adults. Subsequently, various concentrations of citrates were added to adult UMMs to evaluate the changes in the crystal-cell adhesion inhibitory activity of UMMs. RESULTS: Pediatric UMMs more strongly inhibited the adhesion of calcium oxalate monohydrate crystals to cultured Madin-Darby canine kidney cells at a concentration of 0.1 mg/mL compared with adult UMMs. In addition, pediatric UMMs contained higher proportions of fibronectin and glycosaminoglycans, both of which exhibit crystal-cell adhesion inhibitory activity. When citrates were added to adult UMMs, the crystal-cell adhesion inhibitory activity of UMMs was increased in a dose-dependent manner. However, citrates alone did not result in any differences in the inhibitory activity at any of the three different concentrations. CONCLUSIONS: We speculate that the incidence of pediatric urolithiasis is low because pediatric UMMs more potently inhibit the adhesion of calcium oxalate crystals to renal tubular cells or because the higher proportion of citrates in pediatric urine enhances the crystal-cell adhesion inhibitory activity of UMMs in a dose-dependent manner.