Lactulose Ingestion Induces a Rapid Increase in Genus Bifidobacterium in Healthy Japanese: A Randomised, Double-Blind, Placebo-Controlled Crossover Trial.

Oral administration of a low dose of lactulose increases the abundance of genus Bifidobacterium in the large intestine; however, the details of the daily variation in Bifidobacterium have not been researched. To observe how the intestinal microbiota, including Bifidobacterium, change, especially immediately after the initiation of ingestion, we conducted a randomised, placebo-controlled, double-blind crossover study of ingestion of 4 g lactulose/day for 2 weeks in 36 healthy Japanese (including males and females). The primary outcome was the percentage of Bifidobacterium in the faecal bacteria. In the lactulose-treatment group, the percentage of Bifidobacterium was already significantly higher 2 days after starting lactulose ingestion than in the placebo group (20.5 ± 1.2% vs. 17.1 ± 1.2%, p = 0.021). Significant differences were maintained, gradually widening, until the end of the 2-week intervention period. There were significant increases in the percentage and the number of Bifidobacterium with ingestion of 4 g lactulose/day for 2 weeks, but no significant changes in the beta diversity of the intestinal microbiota between lactulose and placebo ingestion. The percentage of Bifidobacterium in the faecal bacteria returned to its original level within a week of the end of intervention with lactulose.

Clinical characteristics and treatment status of pustulotic arthro-osteitis: A single-center study involving 51 cases.

Pustulotic arthro-osteitis (PAO) is a major complication of palmoplantar pustulosis (PPP). In orthopedic surgery outpatient clinics, PPP patients with osteoarticular symptoms are seen frequently, but PAO's clinical features remain not well known. To determine Japanese patients' clinical features and treatment status with PAO, we conducted a single-center retrospective epidemiologic survey. Clinical features, including gender, age, smoking habit, the onset pattern, interval between skin manifestation and osteoarticular symptoms, and the incidence of sternoclavicular joint lesions, axial and peripheral joint lesions, were examined. The association between physical status and image findings by X-ray, computed tomography, bone scintigraphy with Technetium99 , or magnetic resonance imaging was evaluated. The distribution pattern of peripheral joint lesions and the treatment status were evaluated. We identified 51 patients, 10 men and 41 women, with PAO. The average age was 48 years and 59% were smokers. The frequency of onset patterns was skin-leading type (63%), simultaneous onset (18%), and osteoarticular leading type (16%). The average interval between skin involvement and osteoarticular involvement in skin-leading type was significantly longer than that in osteoarticular leading type (7.1 years vs. 2.0 years). A sternoclavicular joint (SCJ) lesion was detected in 65% cases, and the physical findings of SCJ were significantly related to the image findings. Axial and peripheral joint lesions were detected in the same ratio (23 cases, 45%). In the peripheral joints, the finger joint was the most common (26%), followed by the shoulder joint (21%). Patients were treated with nonsteroidal anti-inflammatory drugs (76%), followed by conventional synthetic disease-modifying antirheumatic drugs (DMARDs) (29%) and biological DMARDs (9.8%). Tonsillectomy was performed in 11 cases. In conclusion, PAO more frequently involves SCJ in middle-aged women who smoke. Given that osteoarticular leading type was detected in 16% cases, seronegative oligoarthritis patients should be monitored for PPP, leading to a diagnosis of PAO.

Bifidobacterium response to lactulose ingestion in the gut relies on a solute-binding protein-dependent ABC transporter.

This study aims to understand the mechanistic basis underlying the response of Bifidobacterium to lactulose ingestion in guts of healthy Japanese subjects, with specific focus on a lactulose transporter. An in vitro assay using mutant strains of Bifidobacterium longum subsp. longum 105-A shows that a solute-binding protein with locus tag number BL105A_0502 (termed LT-SBP) is primarily involved in lactulose uptake. By quantifying faecal abundance of LT-SBP orthologues, which is defined by phylogenetic analysis, we find that subjects with 107 to 109 copies of the genes per gram of faeces before lactulose ingestion show a marked increase in Bifidobacterium after ingestion, suggesting the presence of thresholds between responders and non-responders to lactulose. These results help predict the prebiotics-responder and non-responder status and provide an insight into clinical interventions that test the efficacy of prebiotics.

A study of the prebiotic effect of lactulose at low dosages in healthy Japanese women.

To investigate the prebiotic effect of lactulose at low dosages, we assessed changes in defaecation frequency following ingestion of 1, 2, or 3 g/day of lactulose for 2 weeks. Each test was carried out after a 2-week washout period. This was an open-label, before-after trial that enrolled 26 healthy Japanese women. The defaecation frequency, number of defaecation days, and number of faecal bifidobacteria increased significantly compared with before ingestion of 1, 2, and 3 g/day of lactulose. These results suggest that even 1 g/day of lactulose could have a prebiotic effect.

Acute renal failure in an adult cat following oral administration of fosfomycin.

CASE SUMMARY: A spayed female mixed breed cat of unknown age (presumably more than 9 years old), weighing 2.9 kg, was presented with a 4 day history of lethargy, anorexia and vomiting following oral administration of calcium fosfomycin (20 mg/kg q12h). A serum biochemical analysis revealed a dramatic increase in the levels of blood urea nitrogen (>140 mg/dl) and creatinine (15.3 mg/dl), and hypercalcaemia (13.1 mg/dl), hyperphosphataemia (13.3 mg/dl) and hyperkalaemia (6.1 mmol/l). The cat was hospitalised and treated with infusion therapy. However, the renal function and clinical signs did not improve with any treatment. The cat was euthanased upon the owner's request. Histopathological analysis of the kidneys revealed acute tubular necrosis in the cortex. RELEVANCE AND NOVEL INFORMATION: The present case report provides, for the first time, clinical and histopathological evidence for acute renal failure induced by oral administration of fosfomycin in an adult cat. It is highly advisable that fosfomycin should not be used in either young or adult cats.

[Milk, Daily products and Bone health.The effect of lactulose on bone health.]

Lactulose is a non-digestible oligosaccharide, consisting of galactose and fructose. Bifidobacteria in the large intestine assimilate and metabolize lactulose, which has not been degraded or absorbed by humans, and they subsequently proliferate. Predominant bifidobacteria release short chain fatty acids, such as acetic acid and lactic acid, into the intestinal tract by lactulose metabolization, which lowers the intraluminal pH. As a result, the calcium that has flowed into the large intestine without absorption in the small intestine is solubilized and absorbed in the large intestine. So that means continuous ingestion of lactulose might contribute to bone health by increasing the absorption efficiency of calcium.

N-terminal vacuolar sorting signal at the mouse antibody alters the N-linked glycosylation pattern in suspension-cultured tobacco BY2 cells.

Recombinant DNA technology enables the use of plants as the host for the production of pharmaceutical proteins, such as antibodies. The glycosylation of recombinant proteins plays physiological and biological roles. However, because glycosylation in plants is different from that in human cells, the development of glycoengineering is required. In plant cells, glycan structures are shown to correlate with the localization of the recombinant protein produced. In this study, the vacuolar sorting signal (VSS) of sporamin was fused to the heavy (H) and light (L) chains of a mouse monoclonal antibody (mAb), and the mAb was produced in suspension-cultured tobacco BY2 cells. The sugar chain structures were determined by high-performance liquid chromatography, exoglycosidase digestion, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Typical plant glycans with α1,3-fucosylation and/or ß1,2-xylosylation derived from mAb with the VSS-fused H-chain (mIgG1000) and mAb with the VSS-fused H- and L-chain (mIgG1010) occupied the large amount of the total N-glycans, 72.1% and 85.0%, respectively, such as those derived from mAb without VSS (mIgG0000), 74.6% (Fujiyama et al., J. Biosci. Bioeng., 101, 212-218, 2006). In contrast, the typical plant glycan structure Man3FucXylGlcNAc2 particularly in vacuoles accounted for 37.8% of the total sugar chains derived from mIgG1000 and 58.5% of those derived from mIgG1010 compared with 24.3% of those derived from mIgG0000. These results suggest that the sporamin signal peptide fused to mAb acts as a VSS and leads to the increase in the amount of Man3FucXylGlcNAc2, which is the main N-glycan structure in vacuoles.

Prevalence of antibodies to Japanese encephalitis virus among inhabitants in Java Island, Indonesia, with a small pig population.

Japanese encephalitis virus (JEV) is maintained through a transmission cycle between amplifier swine and vector mosquitoes in a peridomestic environment. Thus, studies on natural JEV activities in an environment with a small size of pig population have been limited. Here, we surveyed antibodies against JEV in inhabitants of Jakarta and Surabaya located in Java Island (Indonesia), which has a small swine population. Overall, 2.2% of 1,211 sera collected in Jakarta and 1.8% of 1,751 sera collected in Surabaya had neutralizing antibody titers of >or= 1:160 (90% plaque reduction). All the samples with titers of >or= 1:160 against JEV were also examined for neutralizing antibodies against each of four dengue viruses to confirm that JEV antibody prevalences obtained in the present survey were not attributable to serologic cross-reactivities among flaviviruses distributed in Java. These results indicated that people in Java Island are exposed to natural JEV infections despite a small swine population.

Change in glycosylation pattern with extension of endoplasmic reticulum retention signal sequence of mouse antibody produced by suspension-cultured tobacco BY2 cells.

The production of antibodies using plants as bioreactors has been realized. Because sugar chain structures on recombinant proteins are a cause of concern, remodeling technology is highly promising. Localizing recombinant proteins in the endoplasmic reticulum (ER) affects the glycosylation pattern in transgenic plants. Previously, a mouse antibody produced by suspension-cultured tobacco BY2 cells has sugar chains with possible glycoepitopes as the predominant structures. In this study, we extended the Lys-Asp-Glu-Leu (KDEL) ER retention signal sequence over the heavy (H) and light (L) chains of the antibody and expressed the altered antibody in tobacco BY2 cells to study the effect of the KDEL sequence on glycosylation. For the antibody with the KDEL-extended H-chains, glycans with beta(1,2)-xylose or alpha(1,3)-fucose residues accounted for 49% of the total glycans. Meanwhile, for the antibody with the KDEL-extended H- and L-chains, glycans with xylose or fucose accounted for 38% of the total glycans. Although the addition of an ER retention signal shifted the dominant glycan structures of the KDEL-extended antibody to high-mannose-type structures, some of the antibodies escaped the retrieval system during intracellular traffic and were then modified by xylosylation or fucosylation.

N-linked glycan structures of human lactoferrin produced by transgenic rice.

Human lactoferrin was produced in genetically engineered rice. N-linked glycan structures of recombinant human lactoferrin were determined. The oligosaccharides liberated by hydrazinolysis were labeled with 2-aminopyridine (PA). The PA-labeled glycans were purified by reverse-phase and size-fractionation HPLCs. The structures of these glycans were identified by HPLC, exoglycosidase digestion, and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The glycan structures determined were ManFucXylGlcNAc(2) (3.4%), Man(2)FucGlcNAc(2) (2.1%), Man(3)FucGlcNAc(2) (2.5%), Man(3)FucXylGlcNAc(2) (42.5%), two isomers of Man(2)FucXylGlcNAc(2) (39.1%), Man(3)XylGlcNAc(2) (6.5%), and Man(2)XylGlcNAc(2) (3.9%).