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The long-held belief that degeneration of the cholinergic basal forebrain was central to Alzheimer's disease (AD) pathogenesis and occurred early in the disease process has been questioned recently. In this regard, changes in some cholinergic basal forebrain (CBF) markers (e.g. the high affinity trkA receptor) but not others (e.g., cortical choline acetyltransferase [ChAT] activity, the number of ChAT and vesicular acetylcholine transporter-immunoreactive neurons) suggest specific phenotypic changes, but not frank neuronal degeneration, early in the disease process. The present study examined the expression of the low affinity p75 neurotrophin receptor (p75(NTR)), an excellent marker of CBF neurons, in postmortem tissue derived from clinically well-characterized individuals who have been classified as having no cognitive impairment (NCI), mild cognitive impairment (MCI), and mild AD. Relative to NCI individuals, a significant and similar reduction in the number of nucleus basalis p75(NTR)-immunoreactive neurons was seen in individuals with MCI (38%) and mild AD (43%). The number of p75(NTR)-immunoreactive nucleus basalis neurons was significantly correlated with performance on the Mini-Mental State Exam, a Global Cognitive Test score, as well as some individual tests of working memory and attention. These data, together with previous reports, support the concept that phenotypic changes, but not frank neuronal degeneration, occur early in cognitive decline. Although there was no difference in p75(NTR) CBF cell reduction between MCI and AD, it remains to be determined whether these findings lend support to the hypothesis that MCI is a prodromal stage of AD.  相似文献   
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Journal of Public Health - Screening services for early detection of patients is one of the important capabilities of the health system with a proper referral system. In the crisis of respiratory...  相似文献   
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Implant wear and corrosion have been associated with adverse tissue reactions that can lead to implant failure. Wear and corrosion products are therefore of great clinical concern. For example, Co2+ and Cr3+ originating from CoCrMo‐based implants have been shown to induce a proinflammatory response in macrophages in vitro. Previous studies have also shown that the polarization of macrophages by some proinflammatory stimuli is associated with a hypoxia‐inducible factor‐1α (HIF‐1α)‐dependent metabolic shift from oxidative phosphorylation (OXPHOS) towards glycolysis. However, the potential of Co2+ and Cr3+ to induce this metabolic shift, which plays a determining role in the proinflammatory response of macrophages, remains largely unexplored. We recently demonstrated that Co2+, but not Cr3+, increased oxidative stress and decreased OXPHOS in RAW 264.7 murine macrophages. In the present study, we analyzed the effects of Co2+ and Cr3+ on glycolytic flux and HIF‐1α stabilization in the same experimental model. Cells were exposed to 6 to 24 ppm Co2+ or 50 to 250 ppm Cr3+. Glycolytic flux was determined by analyzing extracellular flux and lactate production, while HIF‐1α stabilization was analyzed by immunoblotting. Results showed that Co2+, and to a lesser extent Cr3+, increased glycolytic flux; however, only Co2+ acted through HIF‐1α stabilization. Overall, these results, together with our previous results showing that Co2+ increases oxidative stress and decreases OXPHOS, suggest that Co2+ (but not Cr3+) can induce a HIF‐1α‐dependent metabolic shift from OXPHOS towards glycolysis in macrophages. This metabolic shift may play an early and pivotal role in the inflammatory response induced by Co2+ in the periprosthetic environment.  相似文献   
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Sexuality and Disability - Sexual problems of hemodialysis patients are one of the most significant factors affecting their quality of life and families. On the other hand, an essential part of the...  相似文献   
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A comprehensive field study of the levels of aromatic petroleum hydrocarbons in water was conducted throughout the coastal areas of Bahrain in the Arabian Gulf. Fifty monitoring stations were established, and each station was visited twice during the investigation. Monitoring stations included industrial, ports, marinas and mooring stations, public beaches and residential stations, domestic outfall stations, and remote background stations. The results of the survey revealed marked temporal and spatial variations in petroleum hydrocarbons concentrations in the sea water analyzed. The highest overall mean value was 88.5 g/L measured in industrial areas and the lowest was 16.1 g/L chrysene equivalent at remote stations. Generally, levels of petroleum hydrocarbons were high in all stations compared to other coastal areas in the Gulf, indicating a chronic oil pollution problem. The results revealed significant temporal variations, however, no specific patterns could be identified.The total land-based oil inputs to the coastal waters is estimated to be 31 metric tonnes/year measured as aromatic petroleum hydrocarbons.  相似文献   
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Extracellular adenosine 5-triphosphate (ATP) induced a characteristic, dose-dependent release of histamine and prostaglandin D2 (PGD2) from rat peritoneal mast cells. The process was relatively slow, non-cytotoxic, maximal at physiological pH and dependent on external calcium. Strontium and barium ions were able to substitute for calcium, although higher concentrations were required for maximal release. Cells stimulated in the absence of calcium progressively lost the ability to respond to subsequent reintroduction of the cation. The secretion of histamine induced by ATP was largely unaffected by the anti-asthmatic drugs disodium cromoglycate and nedocromil sodium but was inhibited by structurally related flavonoids and by cAMP-active drugs. Importantly, the non-hydrolysable guanosine 5-triphosphate (GTP) analogue, GTP--S, elicited a dose-dependent release of histamine when introduced into mast cells permeabilized with ATP in the absence of external calcium. ATP thus appears to be a useful cell permeabilizing tool with which to study the biochemical processes involved in mast cell activation.  相似文献   
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