Multivariate comparison of elemental concentrations in human teeth

R-mode factor analysis was applied to characterize the chemical composition of human teeth investigated by particle induced X-ray emission (PIXE), Rutherford backscattering spectrometry (RBS) and X-ray fluorescence (XRF) techniques. The approach developed in this study enabled the separation between essential mineral teeth components and the pollutants deposited in teeth tissues during the human life. The three independent sources of metals incorporated in human teeth were found. The first source, representing about 43% of the variance of the concentration data, was characterized by pollutant elements of power industry emissions. The second factor was loaded with toxic elements of general urban pollution. The third factor represented the tooth source as it contained mainly large fractions of the mineral components of the tooth tissue as Ca and K.     

Exercise improves cognition and hippocampal plasticity in APOE ε4 mice

BackgroundHuman studies on exercise, cognition, and apolipoprotein E (APOE) genotype show that ε4 carriers may benefit from regular physical activity.MethodsWe examined voluntary wheel-running, memory, and hippocampal plasticity in APOE ε3 and APOE ε4 transgenic mice at 10–12 months of age.ResultsSedentary ε4 mice exhibited deficits in cognition on the radial-arm water maze (RAWM), a task dependent on the hippocampus. Six weeks of wheel-running in ε4 mice resulted in improvements on the RAWM to the level of ε3 mice. Hippocampal brain-derived neurotrophic factor (BDNF) levels were similar in ε3 and ε4 mice, and after exercise BDNF was similarly increased in both ε3 and ε4 mice. In sedentary ε4 mice, tyrosine kinase B (Trk B) receptors were reduced by 50%. Exercise restored Trk B in ε4 mice to the level of ε3 mice, and in ε4 mice, exercise dramatically increased synaptophysin, a marker of synaptic function.ConclusionsOur results support the hypothesis that exercise can improve cognitive function, particularly in ε4 carriers.     

Use of pressure-hold test for sterilizing filter membrane integrity in radiopharmaceutical manufacturing

The bubble point test is the de facto standard for postproduction filter membrane integrity test in the radiopharmaceutical community. However, the bubble point test depends on a subjective visual assessment of bubbling rate that can be obscured by significant diffusive gas flows below the manufacturer's prescribed bubble point. To provide a more objective means to assess filter membrane integrity, this study evaluates the pressure-hold test as an alternative to the bubble point test. In our application of the pressure-hold test, the nonsterile side of the sterilizing filter is pressurized to 85% of the predetermined bubble point with nitrogen, the filter system is closed off from the pressurizing gas and the pressure is monitored over a prescribed time interval. The drop in pressure, which has a known relationship with diffusive gas flow, is used as a quantitative measure of membrane integrity. Characterization of the gas flow vs. pressure relationship of each filter/solution combination provides an objective and quantitative means for defining a critical value of pressure drop over which the membrane is indicated to be nonintegral. The method is applied to sterilizing filter integrity testing associated with the commonly produced radiopharmaceuticals, [¹⁸F]FDG and [¹¹C]PIB. The method is shown to be robust, practical and amenable to automation in radiopharmaceutical manufacturing environments (e.g., hot cells).     

The prevalence of chromium allergy in Denmark is currently increasing as a result of leather exposure

Background Chromium allergy has traditionally been caused by occupational skin contact with cement. In 1983, Danish legislation made the addition of ferrous sulphate compulsory in cement to reduce the water‐soluble chromium content to not more than 2 ppm. An effect from this intervention has previously been demonstrated among Danish construction workers. Objectives To investigate the development of chromium allergy among patients with dermatitis tested between 1985 and 2007 in Denmark. Furthermore, to determine causative exposures in patients with chromium allergy. Patients and methods A retrospective analysis of patch test data was performed (n = 16 228) and charts from patients with chromium allergy were reviewed. Comparisons were made using a χ² test. Logistic regression analyses were used to test for associations. Results The prevalence of chromium allergy decreased significantly from 3·6% in 1985 to 1% in 1995 (P_trend < 0·001) but increased to 3·3% in 2007 (P_trend < 0·001). The frequency of clinically relevant cement exposure decreased significantly among patients with chromium allergy from 12·7% in 1989–1994 to 3·0% (P < 0·01) in 1995–2007, whereas the frequency of relevant leather exposure increased significantly from 24·1% during 1989–1994 to 45·5% during 1995–2007 (P < 0·02). Conclusions Chromium allergy is currently increasing in Denmark due to leather exposure.     

Detergent fractionation with subsequent subtractive suppression hybridization as a tool for identifying genes coding for plasma membrane proteins

Abstract:  The identification of tumor-specific proteins located at the plasma membrane is hampered by numerous methodological pitfalls many of which are associated with the post-translational modification of such proteins. Here, we present a new combination of detergent fractionation of cells and of subtractive suppression hybridization (SSH) to gain overexpressed genes coding for membrane-associated or secreted proteins. Fractionation of subcellular components by digitonin allowed sequestering mRNA of the rough Endoplasmatic reticulum and thereby increasing the percentage of sequences coding for membrane-bound proteins. Fractionated mRNAs from the cutaneous T-cell lymphoma (CTCL) cell line HuT78 and from normal peripheral blood monocytes were used for SSH leading to the enrichment of sequences overexpressed in the tumor cells. We identified some 21 overexpressed genes, among them are GPR137B, FAM62A, NOMO1, HSP90, SLIT1, IBP2, CLIF, IRAK and ARC. mRNA expression was tested for selected genes in CTCL cell lines, skin specimens and peripheral blood samples from CTCL patients and healthy donors. Several of the detected sequences are clearly related to cancer, but have not yet been associated with CTCL. qPCR confirmed an enrichment of these mRNAs in the rough endoplasmic reticulum fraction. RT-PCR confirmed the expression of these genes in skin specimens and peripheral blood of CTCL patients. Western blotting verified protein expression of HSP90 and IBP2 in HuT78. GPR137B could be detected by immunohistology in HuT78 and in keratinocytes of dysplastic epidermis, but also in sweat glands of healthy skin. In summary, we developed a new technique, which allows identifying overexpressed genes coding preferentially for membrane-associated proteins.     

Evaluation of gastric emptying in familial and sporadic Parkinson disease

ObjectiveTo assess for the presence of gastric dysmotility in familial and sporadic Parkinson disease (PD).Methods10 subjects with familial Parkinson disease (fPD), 35 subjects with sporadic Parkinson disease (sPD), and 15 controls, all from academic tertiary care movement disorders centers, were studied. fPD was defined as the presence of at least 2 affected individuals within 2–3 consecutive generations in a family. Molecular genetic analysis has not revealed, thus far, any known genomic abnormality in these families. Gastric emptying was assessed by dynamic abdominal scintigraphy over 92 min following ingestion of a solid meal containing 99mTc-labeled colloid of 40 MBq activity. The main outcome measures were gastric emptying half-time and radiotracer activity over the gastric area at 46 and at 92 min.ResultsGastric emptying time was delayed in 60% of subjects with PD. In comparison to mean t_1/2 of 38 ± 7 min in controls, mean t_1/2 was 58 ± 25 min in fPD (p = 0.02) and 46 ± 25 min in sPD (p = 0.10). Both fPD and sPD groups included subjects with delayed gastric emptying at an early stage of disease.ConclusionsPatients with fPD showed significantly delayed gastric emptying in comparison to normal age-matched individuals. Further studies of gastrointestinal dysfunction in PD, particularly fPD, are warranted.