β-N-methylamino-L-alanine Enhances Neurotoxicity Through Multiple Mechanisms

The idea that the environmental toxin β-N-methylamino-l-alanine (BMAA) is involved in neurodegenerative diseases on Guam has risen and fallen over the years. The theory has gained greater interest with recent reports that BMAA is biomagnified, is widely distributed around the planet, and is present in the brains of Alzheimer\u27s patients in Canada. We provide two important new findings. First, we show that BMAA at concentrations as low as 10 μM can potentiate neuronal injury induced by other insults. This is the first evidence that BMAA at concentrations below the mM range can enhance death of cortical neurons and illustrates potential synergistic effects of environmental toxins with underlying neurological conditions. Second, we show that the mechanism of BMAA toxicity is threefold: it is an agonist for NMDA and mGluR5 receptors, and induces oxidative stress. The results provide further support for the hypothesis that BMAA plays a role in neurodegenerative diseases

Energy level statistics in weakly disordered systems: from quantum to diffusive regime

We calculate two-point energy level correlation function in weakly disorderd metallic grain with taking account of localization corrections to the universal random matrix result. Using supersymmetric nonlinear sigma model and exactly integrating out spatially homogeneous modes, we derive the expression valid for arbitrary energy differences from quantum to diffusive regime for the system with broken time reversal symmetry. Our result coincides with the one obtained by Andreev and Altshuler [Phys. Rev. Lett. 72, 902 (1995)] where homogeneous modes are perturbatively treated.Comment: 12 pages, no figure, REVTeX 3.1 with pLaTeX 2e; v2: minor grammatical change

Point-of-care versus central testing of hemoglobin during large volume blood transfusion.

BACKGROUND: Point-of-care (POC) hemoglobin testing has the potential to revolutionize massive transfusion strategies. No prior studies have compared POC and central laboratory testing of hemoglobin in patients undergoing massive transfusions. METHODS: We retrospectively compared the results of our point-of-care hemoglobin test (EPOC®) to our core laboratory complete blood count (CBC) hemoglobin test (Sysmex XE-5000™) in patients undergoing massive transfusion protocols (MTP) for hemorrhage. One hundred seventy paired samples from 90 patients for whom MTP was activated were collected at a single, tertiary care hospital between 10/2011 and 10/2017. Patients had both an EPOC® and CBC hemoglobin performed within 30 min of each other during the MTP. We assessed the accuracy of EPOC® hemoglobin testing using two variables: interchangeability and clinically significant differences from the CBC. The Clinical Laboratory Improvement Amendments (CLIA) proficiency testing criteria defined interchangeability for measurements. Clinically significant differences between the tests were defined by an expert panel. We examined whether these relationships changed as a function of the hemoglobin measured by the EPOC® and specific patient characteristics. RESULTS: Fifty one percent (86 of 170) of paired samples\u27 hemoglobin results had an absolute difference of ≤7 and 73% (124 of 170) fell within ±1 g/dL of each other. The mean difference between EPOC® and CBC hemoglobin had a bias of - 0.268 g/dL (p = 0.002). When the EPOC® hemoglobin was \u3c 7 g/dL, 30% of the hemoglobin values were within ±7, and 57% were within ±1 g/dL. When the measured EPOC® hemoglobin was ≥7 g/dL, 55% of the EPOC® and CBC hemoglobin values were within ±7, and 76% were within ±1 g/dL. EPOC® and CBC hemoglobin values that were within ±1 g/dL varied by patient population: 77% for cardiac surgery, 58% for general surgery, and 72% for non-surgical patients. CONCLUSIONS: The EPOC® device had minor negative bias, was not interchangeable with the CBC hemoglobin, and was less reliable when the EPOC® value was \u3c 7 g/dL. Clinicians must consider speed versus accuracy, and should check a CBC within 30 min as confirmation when the EPOC® hemoglobin is \u3c 7 g/dL until further prospective trials are performed in this population

Dysregulation of Arginase Isoenzymes in FL-HCC: Investigating the Impact of Nonspecific Arginase-Isoform Antibodies on the Market

In this project, we investigated the expression of the isoenzymes Arginase 1 (ARG1) and Arginase 2 (ARG2) in fibrolamellar hepatocellular carcinoma (FL-HCC) tissue samples. Previous proteomics data had predicted ARG2 to be up-regulated in FL-HCC without clear indication of dysregulation in ARG1. We utilized western blot analysis to determine protein expression by comparing five FL-HCC patient samples to three normal liver tissue samples. During the analysis, we discovered the non-specificity of several commercially bought ARG2 antibodies. This led to the design and execution of various experiments aimed at troubleshooting and identifying a commercially available ARG2 antibody that is specific for the ARG2 isotype. Once the ARG2 isotype-specific antibody was identified, it was used for western blot analysis. Our data concluded that ARG2 expression is up-regulated in FL-HCC. In addition, our data shows that ARG1 expression is sample-specific, pointing to possible stage-specific dysregulation of ARG1 in FL-HCC tumor samples. Overall, our project demonstrates the importance of verifying isoform-specific antibodies while determining the expression of Arginase isoforms in tissue samples. Our findings have important implications for FL-HCC research, as they suggest that targeting ARG2 may be a promising therapeutic strategy. Additionally, our study highlights the need for careful validation of isoform-specific antibodies in cancer research, which can improve the accuracy and reliability of experimental results

Cytotoxicity of oleandrin isolated from the leaves of Nerium indicum Mill. on several human cancer cell lines

Finding anticancer drugs from natural resources still proceeds. Oleandrin isolated from Nerium indicum Mill. inhibited the growth of mieloma cell line in vitro better than that of vincristine sulphate. This study was aimed to determine the cytotoxic effect of oleandrin on various human cancer cell lines. Cytotoxic test of oleandrin on seven human cancer cell lines was done by SRB-method. The analysis was conducted by comparing the ID50 of oleandrin with that of doxorubicin and cisplatin as positive controls. This result indicated that oleandrin possessed the best cytotoxic effect on breast cancer (MCF7) with ID50 at 8.85 nM. Keywords : Oleandrin, cytotoxicity, human cancer cells, ID5

Assay method validation of triamcinolone acetonide (TA) to support the investigation of TA-loaded nanoparticles

Theaim of this study was to develop the valid analytical method which used for the assay of triamcinolone acetonide (TA) in the investigation of TA loaded nanoparticle formulations. High Performance Liquid Chromatography(HPLC) method was applied in  his study by using an Econosil column,C1810 m, 250x 4.6mm (Alltech Associates Inc, PA,USA )as the stationary phase. Themobile phase consisted of a composition of acetonitrile (ACN) and 20mM phosphate buffer solution (pH 4.2) in the proportion of 50:50 v/v. The HPLCassay of TA was validated for selectivity, linearity, precision, ecovery (accuracy),sensitivity and stability of TA during the assay. Results showed that the concentration of TA in the sample scan be determined against the standard in the concentration range of calibration curve. The system precision and level of recovery were considered to be acceptable, and the method was selective and sensitive.Key words:triamcinoloneacetonide,assay,validatio