Neurochemical dementia diagnostics (NDD) can significantly improve the clinically based categorization of patients with early dementia disorders, and the cerebrospinal fluid (CSF) concentrations of amyloid b peptides ending at the amino acid position of 42 (Abx-42 and Ab1-42) are widely accepted biomarkers of Alzheimer's disease (AD). However, in subjects with constitutively high-or low-CSF concentrations of total Ab peptides (tAb), the NDD interpretation might lead to erroneous conclusions as these biomarkers seem to correlate better with the total Ab load than with the pathological status of a given patient in such cases. In this multicenter study, we found significantly increased CSF concentrations of phosphorylated Tau (pTau181) and total Tau in the group of subjects with high CSF Abx-40 concentrations and decreased Abx-42/x-40 concentration ratio compared with the group of subjects with low CSF Abx-40 and normal Ab ratio (p < 0.001 in both cases). Furthermore, we observed significantly decreased Ab ratio (p < 0.01) in the group of subjects with APOE e4 allele compared with the group of subjects without this allele. Surprisingly, patients with low-Abx-40 and the decreased Ab ratio characterized with decreased pTau181 (p < 0.05), and unaltered total Tau compared with the subjects with high Abx-40 and the Ab ratio in the normal range. We conclude that the amyloid b concentration ratio should replace the 'raw' concentrations of corresponding Ab peptides to improve reliability of the neurochemical dementia diagnosis.
the oral administration of metallic colloids, in particular colloidal silver protein, has been reported to have toxic effects (2 ). Despite this, dozens of companies sell metal colloids as nutritional supplements.Many metal colloids have been rebranded as "nano" compounds to further intensify the public's interest in their utility. Although clinical concern about the use of colloidal metallic compounds is longstanding, their effects on laboratory tests have not been investigated. These particles are of particular concern because their small size allows high oral bioavailability, accumulation within the blood, and excretion through the kidneys (5 ). We were interested to know whether metal colloids might cause interference in clinical chemistry tests of blood and urine.We tested 4 nutraceutical products: Mesogold, Mesosilver, Mesocopper, and Mesoplatinum [Purest Colloids, Inc.; daily recommended doses ranged from 50 to 150 g (4 )]. These were colloidal suspensions of nonionic metal with 1-to 10-nm diameter particles. The concentrations of copper, silver, platinum, and gold measured by National Medical Services, Inc. were 0.9, 21, 13, and 18 mg/L of each metal, respectively, whereas the manufacturer's stated concentrations were 10, 20, 10, and 10 mg/L, respectively.We tested the mesometals (undiluted and as 1:1 mixtures with saline or pooled serum) for interference in a range of automated assays on a Vitros ® Model 950 AT:
MB phototreatment reduces the in vitro coagulation capacity of FFP, most likely as a result of the effects of an additional freezing and thawing procedure and photooxidation-induced protein damage.
Preanalytical sample handling and storage procedures play an extremely important role in reliably measuring neurochemical dementia diagnostics (NDD) biomarkers: Aβ(1-40), Aβ(1-42), Tau, and pTau181. To test different handling and storage conditions, the following protocols were applied: (a) storage at room temperature for one week, (b) deep-freezing and thawing up to three cycles, (c) deep-freezing, thawing and keeping under +4°C for two days before the analysis, and (d) long-term stability of a deeply frozen sample. Between the first and the seventh day of the storage at room temperature, the percentage of the concentrations (compared to the starting concentrations) fluctuated: 104.3-105.3, 97.6-93.2, 100.6-96.8, and 97.9-90.2 for Aβ(1-40), Aβ(1-42), Tau, and pTau181, respectively. Re-freezing cycles resulted in the percentage fluctuations of the concentrations: 101.1-105.5, 95.4-99.7, 98.3-100.0, and 100.5-101.4 for Aβ(1-40), Aβ(1-42), Tau, and pTau181, respectively. Keeping previously frozen/thawed samples under +4°C for two days resulted in the percentage differences of the concentrations: +15.9, +2.2, -1.1, and -0.1 for Aβ(1-40), Aβ(1-42), Tau, and pTau181, respectively. During long-term stability, the coefficients of linear correlation (R(2)) were: Aβ(1-40), 0.007; Aβ(1-42), 0.02; Tau, 0.011; and pTau181, 0.02, and the corresponding inter-assay coefficients of variation: 13.9%, 13.9%, 11.0%, and 10.7% for Aβ(1-40), Aβ(1-42), Tau, and pTau181, respectively. We conclude that the NDD biomarkers are relatively stable when the cerebrospinal fluid sample is kept at room temperature for about four days; one or two thawing/refreezing cycles do not profoundly affect the biomarkers concentrations, however three cycles result in increased unsystematic variation. The four biomarkers seem to be stable in a sample stored deeply frozen for more than two years.
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