P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating

Tauopathies are neurodegenerative disorders characterized by the accumulation of abnormal tau protein leading to cognitive and/or motor dysfunction. To understand the relationship between tau pathology and behavioral impairments, we comprehensively assessed behavioral abnormalities in a mouse tauopathy model expressing the human P301S mutant tau protein in the early stage of disease to detect its initial neurological manifestations. Behavioral abnormalities, shown by open field test, elevated plus-maze test, hot plate test, Y-maze test, Barnes maze test, Morris water maze test, and/or contextual fear conditioning test, recapitulated the neurological deficits of human tauopathies with dementia. Furthermore, we discovered that prepulse inhibition (PPI), a marker of sensorimotor gating, was enhanced in these animals concomitantly with initial neuropathological changes in associated brain regions. This finding provides evidence that our tauopathy mouse model displays neurofunctional abnormalities in prodromal stages of disease, since enhancement of PPI is characteristic of amnestic mild cognitive impairment, a transitional stage between normal aging and dementia such as Alzheimer's disease (AD), in contrast with attenuated PPI in AD patients. Therefore, assessment of sensorimotor gating could be used to detect the earliest manifestations of tauopathies exemplified by prodromal AD, in which abnormal tau protein may play critical roles in the onset of neuronal dysfunctions

PROTEIN CATABOLIC RATE SHOULD BE NORMALIZED BY IDEAL BODY WEIGHT NOT BY POST-DIALYSIS BODY WEIGHT.

Protein catabolic rate (PCR) is calculated by urea kinetic model thorough the dialysis session and it is recognized as expressing the protein intake in the steady state of dialysis patients. PCR is generally normalized by post-dialysis body weight (BW), expressed as nPCR, however, most dietary guidelines for protein intake are documented as PCR normalized by ideal BW (iPCR). We evaluated which is better nPCR or iPCR to estimate the impact on the patient survival and to use it for dietary education for dialysis patients. 119 chronic dialysis patients whose dialysis vintages were longer than 3 years were selected into this study. The mean age of them was 62.4years old and the mean dialysis vintage was 115.4 months. The patients were divided into 4 groups by each PCR value as less than 0.7, 0.7– 0.9, 0.9–1.1, greater than 1.1 g/Kg/day. Kaplan-Meier analysis was conducted to evaluate the 5–year patient survival in each PCR method. The difference in the patient survival between 4 groups in each PCR method was evaluated by Log-rank test. Among 119 patients 30 patients died and 9 patients were censored out, and the overall 5-year survival rate was 74.4%. There were no significant differences between 4 groups in nPCR. However, a significant risk in the group less than 0.7 g/Kg/day and a significant benefit in the group greater than 1.1 g/Kg/day were observed in iPCR. Both nPCR and iPCR were not independent significant risk factor on the patient survival. Only age and the serum level of CRP were significant risk factor. We concluded the PCR should be normalized by ideal BW not by post-dialysis BW

Diffenreces in mia related factors between hyperglycemic and normoglycemic dialysis patients

It is generally accepted that diabetic dialysis patients have nutritional problems more frequently than non-diabetic patients, which has a close relation to the shortness of their lifetime. We compared the MIA related factors between hyperglycemic and normoglycemic dialysis patients with diabetes.110 diabetic dialysis patients were enrolled in this study and they were divided into the next 2 groups; the hyperglycemic group as GA greater than or equal to 23%, and the normoglycemic group as GA less than 23%. Nutritional status was evaluated by MIS sheet originally established by Kalantar- Zadeh. Nutritional statuses were categorized as Normal, mild malnourished and moderately/severely malnourished based on the total point of MIS. In the normoglycemic group age, dialysis vintage and serum level of CRP were significantly increased as a nutritional category became worsened. On the other hand in the hyperglycemic group there were no significant differences in MIA related factors among the nutritional categories. Various specific issues which might worsen the nutritional status of hyperglycemic dialysis patients were identified. In the normoglycemic patients malnutrition might has progressed in the similar manner of MIA progression observed in non-diabetic dialysis patients. However, in the hyperglycemic patients malnutrition might has progressed by other specific issues and or hyperglycemia itself. The Patients with severe hyperglycemia cannot live long enough to develop MIA syndrome

Protein nenrgy wasting (pew) is subclinically progressive in choronic dialysis patients

Protein energy wasting (PEW) is the most important problem on chronic dialysis patients because it is closely related to the shortness of their lifetime. However, there have been few reports that clarified the body composition changes in chronic hemodialysis patients.We retrospectively analyzed the changes in body composition evaluated by the bioelectrical impedance analysis for 2 years on 188 chronic hemodialysis patients whose dialysis vintage was more than 2 years. The patients were divided into the next 2 groups; the Group A, 108 patients with BW loss less than 2 %, Group B, 80 patients with BW loss greater than or equal to 2 %. The valuables which could estimate the progression of BW loss were determined using the Chi-square test by the comparison of the Group A and B.In all subjects the mean post-dialysis BW was significantly reduced from 57.3 Kg to 56.6 Kg and the LBM was also reduced from 43.1 Kg to 42.6Kg, but the fat volume didn’t change. In the Group A the LBM didn’t change but the fat volume significantly increased. In the Group B both the LBM and the fat volume were significantly reduced. Age was significantly higher and nPCR was lower in the Group B than A. In our facilities 42.5% of the patients reduced their BW but the difference was very small as -1.2 % from the basal level. The results of this study suggest PEW might subclinical progressive even if the patients can keep their BW as changing their muscle to fat on chronic hemodialysis patients. Higher age and lower protein intake are the risk of PEW so we should promote the proper intake of protein and energy especially for elder dialysis patients