Serodiagnosis of <Emphasis Type="Italic">Helicobacter hepaticus</Emphasis> infection in patients with liver and gastrointestinal diseases: western blot analysis and ELISA using a highly specific monoclonal antibody for <Emphasis Type="Italic">H. hepaticus</Emphasis> antigen

Background  

Helicobacter hepaticus infection might be associated with liver and biliary tract diseases. To investigate its pathogenic role, the properties of anti-H. hepaticus serum antibody in patients with liver and diseases were elucidated.     

Anti-diabetic effects of lactic acid bacteria in normal and type 2 diabetic mice

The antidiabetic effects of lactic acid bacteria were investigated using mice. In Experiment 1, normal ICR mice were loaded with sucrose or starch with or without viable Lactobacillus rhamnosus GG cells. GG significantly inhibited postprandial blood glucose levels when administered with sucrose or starch. In Experiment 2, KK-A(y) mice, a model of genetic type 2 diabetes, were given a basal diet containing viable GG cells or viable Lactobacillus delbrueckii subsp. bulgaricus cells for 6 weeks. Viable GG cells significantly inhibited fasting blood glucose, postprandial blood glucose in a glucose tolerance test and HbA1c. Such effects were not shown by viable L. bulgaricus cells. In Experiment 3, the KK-A(y) mice were given a basal diet containing viable GG cells or heat-treated GG cells for 3 weeks. The viable GG cells significantly suppressed fasting blood glucose and impaired glucose tolerance, but the heat-treated GG showed no effects. These results demonstrated that GG decreased the postprandial blood glucose in ICR mice, and that the antidiabetic activity of lactic acid bacteria on the KK-A(y) mice differed depending on the bacterial strain and whether the bacterium is viable when it arrives in the intestine. In the present study, we conclude that the antidiabetic activity may result from continuous inhibition of the postprandial blood glucose through suppression of glucose absorption from the intestine. These findings indicate that specific strains of lactic acid bacterium can be expected to be beneficial for the management of type 2 diabetes.     

Study on species differences in nephropathy induced by FYX-051, a xanthine oxidoreductase inhibitor

To clarify the toxicological aspects of FYX-051, a xanthine oxidoreductase inhibitor, which is currently being developed as a therapeutic agent against gout and hyperuricemia, we performed the study focused on species differences in FYX-051-induced nephropathy. In the repeated toxicology testing by oral administration, nephropathy was seen at 1 mg/kg and more in rats and at 100 mg/kg in dogs, in contrast to no toxicity even at the practical maximum dose (300 mg/kg) in monkeys. The HPLC and LC-MS/MS analyses of intrarenal deposits in dogs have proven that the entity was xanthine. The study on dose dependency of pharmacokinetics, pharmacodynamics, urinary xanthine excretion, and kidney xanthine content by oral administration at 0.3, 1, and 3 mg/kg to rats revealed the involvement of xanthine in the occurrence of nephropathy, thus suggesting that plasma concentrations of FYX-051 can contribute to species differences. Regarding the possible factors of species differences, the daily urinary excretion of total purine metabolites was 30.5- and 6.3-fold greater in rats and dogs, respectively, than in monkeys. Urinary xanthine solubility was 2.3- and 6.3-fold higher in dogs and monkeys, respectively, than in rats. Plasma concentrations of FYX-051 were fivefold higher in rats than in dogs and monkeys, without differences between the latter two species. Therefore, the present study indicated that species differences in nephropathy were produced by the combined effects of purine metabolism, urinary xanthine solubility, and plasma concentrations of FYX-051.     

Antiphospholipid syndrome modifies the clinical features of systemic lupus erythematosus

A 17-year-old woman with arterial and venous thrombosis of the leg diagnosed as antiphospholipid syndrome (APS) associated with systemic lupus erythematosus (SLE) is reported. Her serum C-reactive protein (CRP) was elevated and complement concentrations were normal. Symptoms of APS were improved with prednisolone, when the serum CRP concentration decreased, and low serum complement concentration and white blood cell count appeared. These are characteristic features of SLE. It is suggested that APS is a possible complication of SLE and may modify the clinical features of SLE.     

Evaluation of the Nature and Etiologies of Risk Factors for Diaphyseal Atypical Femoral Fractures

ObjectivesDifferences in mechanisms of subtrochanteric and diaphyseal atypical femoral fractures (AFFs) are speculated in studies that analyzed differences in the patients'' background. However, the etiologies of each type of AFF have not been studied in detail. This study aimed to investigate the nature and etiologies of the risk factors for diaphyseal AFFs.Materials and MethodsEighty consecutive Japanese patients with 91 diaphyseal AFFs (AFF group) and 110 age-matched women with osteoporosis (non-AFF control group) were included. Their clinical data were compared; factors affecting AFFs were investigated, and the etiologies of the risk factors for diaphyseal AFFs were examined.ResultsMultivariate analysis revealed that femoral serrated changes, bisphosphonate or denosumab usage, and lateral and anterior femoral curvatures were risk factors for diaphyseal AFFs (p < 0.0011, p = 0.0137, and p < 0.0001, respectively). Multivariate analyses revealed that serrated changes and low serum 25(OH)D levels affected the lateral curvature (p = 0.0088 and 0.0205, respectively), while serrated changes affected the anterior curvature (p = 0.0006), each significantly affected the femoral curvature. High serum calcium (Ca) levels, lateral femoral curvature, and anterior femoral curvature were predictors of serrated changes (p = 0.0146, 0.0002, and 0.0098, respectively).ConclusionRisk factors for diaphyseal AFFs were bone resorption inhibitor usage, a strong femoral curvature, and serrated changes. Low serum 25(OH)D levels and serrated changes are risk factors for lateral curvature, while a high serum Ca level is a risk factor for serrated changes.     

Operant behavioral analysis of memory loss in monkeys with prefrontal lesions

The effects of dorsolateral prefrontal cortical ablation were examined in rhesus monkeys preoperatively trained to perform two versions of an indirect spatial delayed-response task. In one task (DR I), the stimulus keys that signaled the position of the reward were accessible throughout a trial. Thus, the monkeys could orient to the positive side (‘rehearse’) by continuing to press the correct key during the delay. The other task, DR II, was designed to disrupt bodily orientation and to prevent ‘rehearsal’. In this task the monkeys were required to press an extraneous upper key during the delay. After bilateral ablation of the prefrontal cortex, 3 out of the 4 monkeys easily regained preoperative levels of performance on the DR I task, but all subjects were markedly impaired in the DR II task on which they exhibited strong position preferences. These deficits were ameliorated by eliminating the position biases through training with short delay intervals followed by gradual increments in delay length. Analysis of the location of key presses during each phase of delayed-response trials showed that the monkeys press the correct key in the cue period even when they subsequently made incorrect responses. A consistent finding was that operated monkeys shifted their response to the incorrect key early in the delay period regardless of its duration, whenever the correct side was the nonpreferred side. These results support the idea that delayed-response deficits in monkeys with prefrontal lesions may be due in part to a defect in registering or encoding the correct spatial position in memory rather than to a loss in storage or retrieval processes.     

Acute genetic manipulation of neuronal activity for the functional dissection of neural circuits-a dream come true for the pioneers of behavioral genetics

Abstract: This review summarizes technical development of the functional manipulation of specific neural circuits through genetic techniques in Drosophila. Long after pioneers' efforts for the genetic dissection of behavior using this organism as a model, analyses with acute activation of specific neural circuits have finally become feasible using transgenic Drosophila that expresses light-, heat-, or cold-activatable cation channels by xxx/upstream activation sequence (Gal4/UAS)-based induction system. This methodology opened a new avenue to dissect functions of neural circuits to make dreams of the pioneers into reality.     

Decoctions of Bridelia micrantha and Croton macrostachyus may have anticonvulsant and sedative effects

Bridelia micrantha and Croton macrostachyus are medicinal plants used empirically in traditional medicine to treat epilepsy. In vivo mice model (maximal electroshock, strychnine, pentylenetetrazol, picrotoxin, isonicotinic hydrazide acid)-induced convulsions were used to evaluate the anticonvulsant activities of those plants. Diazepam-induced sleep was used for the evaluation of the sedative properties. B. micrantha protected 100, 80, 80, and 80% of mice against PIC, STR, PTZ and MES-induced seizures, respectively. C. macrostachyus at the doses 34 and 67 mg/kg protected 80, 80, 80 and 60% of mice from PIC, STR, PTZ and MES-induced seizures, respectively. B. micrantha and C. macrostachyus also delayed the onset to seizures in INH test. B. micrantha was more potent than C. macrostachyus in protecting mice against convulsions. The co-administration of the sub effective dose of the decoction of B. micrantha or C. macrostachyus with the sub effective dose of diazepam or clonazepam resulted in a synergistic effect. The decoctions of B. micrantha and C. macrostachyus also exerted sedative activity by increasing the total duration of sleep induced by diazepam and by reducing the latency time to sleep. The effect of the decoctions of B. micrantha and C. macrostachyus suggests the presence of anticonvulsant activities that might show efficacy against secondarily generalized tonic-clonic seizures and primary generalized seizures in humans.