Refeeding Hypophosphatemia in Anorexia Nervosa

Objective: Refeeding in patients with anorexia nervosa (AN) is associated with a risk of refeeding syndrome (RS), which is a disruption in metabolism with a variety of features including hypophosphatemia. We evaluated the risk factors for refeeding hypophosphatemia (RH) during nutritional replenishment in Japanese patients with AN. Methods: We retrospectively examined clinical data for 99 female inpatients (mean age 30.9 ± 10.7 years, range: 9 to 56 years). Results: RH (phosphate <2.3 mg/dL) occurred within 4.8 ± 3.7 days of hospital admission and was still observed at 28 days after admission in 21 of the 99 cases (21.2%). Oral or intravenous phosphate was given to some patients to treat or prevent RH. Patients with RH had a significantly lower body mass index, were older, and had higher blood urea nitrogen than those without RH. Severe complications associated with RH were recorded in only one patient who showed convulsions and disturbed consciousness at day 3 when her serum phosphate level was 1.6 mg/dL. Conclusion: The significant risk factors for RH that we identified were lower BMI, older age, and higher blood urea nitrogen at admission. No significant difference in total energy intake was seen between the RH and no RH groups, suggesting that RH may not be entirely correlated with energy intake. Precisely predicting and preventing RH is difficult, even in patients with AN who are given phosphate for prophylaxis. Thus, serum phosphate levels should be monitored for at least 5-10 days after admission

Association of schizophrenia onset age and white matter integrity with treatment effect of D-cycloserine : a randomized placebo-controlled double-blind crossover study

Background: It has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs. Methods: We performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time. The patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Brief Assessment of Cognition in Schizophrenia (BACS), and other scales. Results: D-cycloserine did not improve positive or negative symptoms or cognitive dysfunction in schizophrenia. The investigation in consideration of the onset age suggests that D-cycloserine may aggravate negative symptoms of early-onset schizophrenia. The better treatment effect of D-cycloserine on BACS was observed when the white matter integrity of the sagittal stratum/ cingulum/fornix stria terminalis/genu of corpus callosum/external capsule was higher, and the better treatment effect on PANSS general psychopathology (PANSS-G) was observed when the white matter integrity of the splenium of corpus callosum was higher. In contrast, the better treatment effect of D-cycloserine on PANSS-G and SANS-IV were observed when the white matter integrity of the posterior thalamic radiation (left) was lower. Conclusion: It was suggested that response to D-cycloserine is influenced by the onset age and white matter integrity

The Effect of Olive Leaf Extract on Hepatic Fat Accumulation in Sprague-Dawley Rats Fed a High-fat Diet

Oleuropein, the active constituent of olive leaf extract, possesses anti-oxidant, hypoglycemic, and hypolipidemic activities. We aimed to assess whether the effect of olive leaf extract on hepatic fat accumulation is preventive or therapeutic. Sprague-Dawley (SD) rats were fed a high-fat diet with (ODOD group) or without (HDHD group) olive leaf extract (1,000 mg/kg diet) for 38 weeks. Another group of rats were fed a high-fat diet for 23 weeks, followed by a high-fat diet with olive leaf extract (1,000 mg/kg diet) for 15 weeks (HDOD group). Serology, histopathology, anti-oxidative activity, and liver fatty acid synthesis were compared to those fed a standard diet (LDLD group) at 26 and 41 weeks of age. The serum levels of total cholesterol, triglyceride and aspartate aminotransferase tended to be lower in the ODOD group as compared to the HDHD and HDOD groups, although there were no significant differences. Histopathologically, hepatic steatosis tended to be less evident in the HDOD and ODOD groups as compared to the HDHD group, and lobular inflammation was not observed in the ODOD group at 26 weeks of age. Hepatic thioredoxin-1 staining tended to be less evident in the ODOD group than in the HDHD and HDOD groups at 41 weeks of age. There were no significant differences in hepatic lipogenic enzyme activities between the ODOD group and HDHD/HDOD groups. Our data suggest that olive leaf extract had a preventive, rather than therapeutic, effect on hepatic steatohepatitis in SD rats fed a high-fat diet

双極性障害におけるグルタミン酸神経伝達異常に関するMRS研究

Background: Previous studies of patients with bipolar disorder (BD) using magnetic resonance spectroscopy (MRS) have shown neurophysiological abnormalities related to the glutamate (Glu)-glutamine (Gln) cycle, membrane turnover, and neuronal integrity, although the results were neither consistent nor conclusive. Recently it has been reported the Gln/Glu ratio is the most useful index, quantifying neuronal-glial interactions and the balance of glutamatergic metabolites In this MRS study, we elucidated the abnormalities of metabolites in a larger sample of patients with BD with a high-field MRI system. Methods: Sixty-two subjects (31 patients with BD and 31 healthy controls [HC]) underwent 3T proton MRS (1H-MRS) of the anterior cingulate cortex (ACC) and left basal ganglia (ltBG) using a stimulated echo acquisition mode (STEAM) sequence. Results: After verifying the data quality, 20 patients with BD and 23 age- and gender-matched HCs were compared using repeated-measures analysis of covariance (ANCOVA). Compared to the HC group, the BD group showed increased levels of Gln, creatine (Cr), N-acetyl aspartate (NAA), choline (Cho), and an increased ratio of Gln to Glu in the ACC, and increased Gln and Cho in the ltBG. These findings remained after the participants with BD were limited to only euthymic patients. After removing the influence of lithium (Li) and sodium valproate (VPA), we observed activated glutamatergic neurotransmission in the ACC but not in the ltBG. Limitations: The present findings are cross-sectional and metabolites were measured in only two regions. Conclusions: Our results support a wide range of metabolite changes in patients with BD involved in glutamatergic neurotransmission, membrane turnover, and neuronal integrity. Moreover, the elevation of Gln/Glu ratio suggested that hyperactivity of glutamatergic neurotransmission in the ACC is a disease marker for BD

Association of schizophrenia onset age and white matter integrity with treatment effect of D-cycloserine: a randomized placebo-controlled double-blind crossover study

Abstract Background It has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs. Methods We performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time. The patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Brief Assessment of Cognition in Schizophrenia (BACS), and other scales. Results D-cycloserine did not improve positive or negative symptoms or cognitive dysfunction in schizophrenia. The investigation in consideration of the onset age suggests that D-cycloserine may aggravate negative symptoms of early-onset schizophrenia. The better treatment effect of D-cycloserine on BACS was observed when the white matter integrity of the sagittal stratum/ cingulum/fornix stria terminalis/genu of corpus callosum/external capsule was higher, and the better treatment effect on PANSS general psychopathology (PANSS-G) was observed when the white matter integrity of the splenium of corpus callosum was higher. In contrast, the better treatment effect of D-cycloserine on PANSS-G and SANS-IV were observed when the white matter integrity of the posterior thalamic radiation (left) was lower. Conclusion It was suggested that response to D-cycloserine is influenced by the onset age and white matter integrity. Trial registration UMIN Clinical Trials Registry (number UMIN000000468 ). Registered 18 August 200