Biochemical characterization of atherosclerotic plaque constituents using FTIR spectroscopy and histology

The behavior of vulnerable atherosclerotic plaques is believed to be closely related to plaque composition. There is a need for an effective in vivo technique for examining plaque constituent properties. In this study, Fourier transform infrared spectroscopy using attenuated total reflectance (FTIR-ATR) was used to assess and analyze the biochemical properties of human atherosclerotic plaques. FTIR spectra clearly revealed prominent spectral features corresponding to plaque constituents of interest: the 2930 cm(-1) and 2850 cm(-1) peaks (indicating the presence of lipids), the 1730 cm(-1) peak (lipid esters), the 1550 cm(-1) and 1650 cm(-1) peaks (fibrous tissues), and the 1100-1000 cm(-1) broad phosphate peak (calcification). Spectral data examined on a qualitative basis correlated well with both gross tissue anatomy and histologic features. Gross spatial mappings of tissue sections of both lipidic and calcified plaques were performed. Spectra from various regions of the plaques demonstrated the evolution of lipid peaks, fibrous tissue peaks, and the phosphate calcification band within the plaques. Histologic analysis corroborated the spectral findings in this study.     

Age-related spatial learning impairment is unrelated to spinophilin immunoreactive spine number and protein levels in rat hippocampus

Age-related impairments in hippocampus-dependent learning and memory tasks are not associated with a loss of hippocampal neurons, but may be related to alterations in synaptic integrity. Here we used stereological techniques to estimate spine number in hippocampal subfields using immunostaining for the spine-associated protein, spinophilin, as a marker. Quantification of the immunoreactive profiles was performed using the optical disector/fractionator technique. Aging was associated with a modest increase in spine number in the molecular layer of the dentate gyrus and CA1 stratum lacunosum-moleculare. By comparison, spinophilin protein levels in the hippocampus, measured by Western blot analysis, failed to differ as a function of age. Neither the morphological nor the protein level data were correlated with spatial learning ability across individual aged rats. The results extend current evidence on synaptic integrity in the aged brain, indicating that a substantial loss of dendritic spines and spinophilin protein in the hippocampus are unlikely to contribute to age-related impairment in spatial learning.     

Communicating with women about mammography

Background/Methods. We report survey results of the types of tools used to communicate with women about breast cancer screening and the content areas included in each tool for member countries of the International Breast Cancer Screening Network (IBSN).Results. In addition to using pamphlets and invitation letters, new technologies are being used such as the Internet which allows for easy updating of information and can provide interactive modules. Several countries have addressed the needs of specific populations such as indigenous populations or blind women. All countries provide basic information, although they do not provide all the same information.Conclusion. More research is needed to understand what women need to make an informed decision about mammography and to learn what the best modalities are to provide this information.     

The role of serum uric acid as an antioxidant protecting against cancer: prospective study in more than 28 000 older Austrian women.

BACKGROUND: It has been hypothesized that serum uric acid (SUA), via its antioxidant properties may protect against carcinogenesis. However, few epidemiological investigations have addressed this association and previous findings are inconsistent. PATIENTS AND METHODS: We prospectively investigated the relation of SUA levels to subsequent cancer mortality in a large cohort of 28613 elderly Austrian women with a median follow-up of 15.2 years. Adjusted Cox proportional hazards models were calculated to evaluate SUA as an independently related factor to fatal cancer events. RESULTS: High SUA (>5.41 mg/dL) was independently associated with increased risk of total cancer mortality (p<0.0001); the adjusted hazard ratio for the highest versus lowest quartile of SUA was 1.27 (1.08-1.48). SUA levels were further positively related to deaths from malignant neoplasms of breast and female genital organs (P = 0.02) and nervous system and unspecified sites (P = 0.02). We found no evidence for an inverse relationship between SUA levels and risk of total or site-specific cancer mortality. CONCLUSION: Our results are contrary to the proposed antioxidant and protective effect of SUA against cancer and rather suggest high SUA concentrations to be associated with outcome possibly reflecting more serious prognostic indication.     

Estrogen increases the number of spinophilin-immunoreactive spines in the hippocampus of young and aged female rhesus monkeys

It is well documented that estrogen increases dendritic spine density in CA1 pyramidal cells of young female rats. However, this effect is attenuated in aged rats. We report here a quantitative analysis of estrogen effects on hippocampal spine number as visualized with antispinophilin in young (6-8 years old) and aged (19-23 years old) female rhesus monkeys, a species with a pattern of female endocrine senescence comparable to that of humans. Monkeys were ovariectomized and administered either vehicle or estradiol cypionate 3 months postovariectomy, followed by an additional dose 3 weeks later, with perfusion 24 hours after the last estrogen treatment. Immunolocalization of spinophilin, a spine-associated protein, was used for quantitative stereologic analyses of total spinophilin-immunoreactive spine numbers in CA1 stratum radiatum and the inner and outer molecular layers of dentate gyrus. In both young and aged female monkeys, the estrogen-treated groups had an increase in spinophilin-immunoreactive spines (37% in young, P <.005; 35% in aged, P <.05) compared with the untreated groups that amounted to more than 1 billion additional immunoreactive spines. The young group also showed a trend toward an estrogen-induced increase in immunoreactive spines in the dentate gyrus outer molecular layer, but this effect was not statistically significant (P =.097). We conclude that spine number in the rhesus monkey hippocampus is highly responsive to estrogen, yet, unlike the female rat, aged female rhesus monkeys retain the capacity for spine induction in response to estrogen. These data have important implications for cognitive effects of estrogen replacement in postmenopausal women and demonstrate that an estrogen replacement protocol that mimics normal physiological cycles with timed, intermittent peaks can have profound neurobiological effects.     

Hepatic endosomal trafficking of lipoprotein-bound endotoxin in rats

Triglyceride-rich lipoproteins (chylomicrons (CM), VLDL) can bind and protect against endotoxin (LPS)-induced shock and mortality in rodents. The protective effect of lipoproteins is in part due to the increased plasma clearance and biliary excretion of LPS. Specifically, CM-LPS complexes are principally removed from the circulation by the liver with a rapid plasma half-life approximating that for CM alone. Thus, we hypothesized that hepatocytes clear CM-bound LPS via known lipoprotein receptors and traffic the toxic macromolecule through the same endosomal pathway employed for the catabolism of triglyceride-rich lipoproteins. To examine the endosomal uptake and biliary excretion of LPS, we isolated early and late hepatic endosomal fractions and hepatic bile from rats following the injection of radiolabeled CM-bound LPS. The uptake of (125)I-LPS was compared in animals that overexpressed either the LDL receptor or the LDL receptor-related protein (LRP) versus untreated control with normal lipoprotein levels. Herein we present data indicating that both the LDL receptor and the LRP participate in the rapid internalization of CM-bound LPS by hepatocytes. Upregulation of the LDL receptor increased the accumulation of (125)I-LPS in late endosomes (P < 0.03). In contrast, increased levels of the LRP were associated with negligible movement of LPS into late endosomes but a trend toward the increased biliary excretion of the radiolabeled macromolecule. Taken together these data further elucidate the role of the liver in the host innate immune response to infection and potentially implicate distinct roles for the LDL receptor and LRP in the catabolism of CM-bound LPS.     

Mikro-Mental-Test Ein Kurzverfahren zum Demenzscreening

Especially in outpatient settings, dementia is still an underdiagnosed syndrome. The Micro-Mental Test has been developed as a short version of the Mini-Mental-Status Examination (MMSE). We examined the reliability and diagnostic validity of a German version (Mikro-Mental Test). We administered the MMSE and the German version of the Micro-Mental Test to 20 inpatients of a geriatric psychiatry hospital (mean age 74.8+/-8.1 years), 55 patients from a cognitive clinic (mean age 71.9+/-9.1 years), and 27 healthy older adults (mean age 68.5+/-4.1 years). Diagnoses made by an experienced psychiatrist according to ICD-10 criteria served as external criteria. The mean duration for testing with the Micro-Mental Test was 8 min, and with the MMSE 15 min. Test-retest analyses showed satisfactory reliability. With regard to sensitivity and specificity, we found comparable diagnostic validity for the MMSE and the Micro-Mental Test. We suggest that, due to its brevity and diagnostic validity, the Micro-Mental Test is a useful tool for dementia screening in an outpatient setting.     

Neuron number in the parahippocampal region is preserved in aged rats with spatial learning deficits

The entorhinal, perirhinal and parahippocampal cortices are anatomically positioned to mediate the bi-directional flow of information between the hippocampus and neocortex. Consistent with this organization, damage involving the parahippocampal region causes significant learning and memory impairment in young subjects. Although recent evidence indicates that neuron death in the hippocampus is not required to account for the effects of normal aging on learning and memory, other findings suggest that changes in parahippocampal interactions with the hippocampus may play a significant role. Prompted by this background, we tested the possibility that age-related deficits in hippocampal learning are coupled with neuron death in the parahippocampal region. The experiments took advantage of a well-characterized rat model of cognitive aging in combination with stereological methods for quantifying neuron number. The results demonstrate that total neuron number in the entorhinal, perirhinal and postrhinal cortices is largely preserved during normal aging. Furthermore, individual variability in hippocampal learning among the aged rats failed to correlate with neuron number in any region examined and there was no indication of selective or disproportionate loss among the aged animals with the most pronounced cognitive impairment. Taken together with earlier findings from the same study population, the results demonstrate that age-related cognitive decline can occur in the absence of significant neuron death in any major, cytoarchitectonically defined component of the hippocampal system. These findings provide an essential framework for identifying the basis of cognitive aging, suggesting that alterations in connectivity and other changes are more likely causative factors.