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61.
Iron is an essential element for life on earth, participating in a plethora of cellular processes where one-electron transfer reactions are required. Its essentiality, coupled to its scarcity in aqueous oxidative environments, has compelled living organisms to develop mechanisms that ensure an adequate iron supply, at times with disregard to long-term deleterious effects derived from iron accumulation. However, iron is an intrinsic producer of reactive oxygen species, and increased levels of iron promote neurotoxicity because of hydroxyl radical formation, which results in glutathione consumption, protein aggregation, lipid peroxidation and nucleic acid modification. Neurons from brain areas sensitive to degeneration accumulate iron with age and thus are subjected to an ever increasing oxidative stress with the accompanying cellular damage. The ability of these neurons to survive depends on the adaptive mechanisms developed to cope with the increasing oxidative load. Here, we describe the chemical and thermodynamic peculiarities of iron chemistry in living matter, review the components of iron homeostasis in neurons and elaborate on the mechanisms by which iron homeostasis is lost in Parkinson's disease, Alzheimer's disease and other diseases in which iron accumulation has been demonstrated.  相似文献   
62.
Mu?oz P  Humeres A 《Biometals》2012,25(4):825-835
Because of the intrinsic ability of iron to catalyze the formation of reactive oxygen species, it has been associated with oxidative stress and neurodegenerative diseases. However, iron deficiency (ID) also negatively impacts various functions of the brain, suggesting that iron plays an important physiological role in neuronal processes such as myelination, synaptogenesis, behavior and synaptic plasticity (SP). ID not only produces changes in the hippocampus, striatum, amygdale or prefrontal cortex, it also affects the interaction among these systems. In both humans and rodents, the perturbations of these structures are associated to cognitive deficits. These cognitive alterations have been well correlated with changes in neural plasticity, the possible cellular substrate of memory and learning. Given that SP is strongly affected by early ID and the lasting-neurological consequences remain even after ID has been corrected, it is important to prevent ID as well as to seek effective therapeutic interventions that reduce or reverse the long-term effects of the ID in the nervous system. This review will give an overview of the literature on the effects of iron deficit in neuronal functions such as behavior, neurotransmission and SP. We also discuss our recent data about the possible oxidative effect of iron on the mechanisms involved in neural plasticity.  相似文献   
63.
??????? 目的 建立健全适于基层医疗单位重症医学科发展的运行模式。方法 以重症胰腺炎为例,比较普通模式和协作小组模式下参与治疗的专业人数、住ICU天数、ICU治疗费用、住院总费用、呼吸机天数、血液滤过总时间、住院期间入液总量和药物占住院费用比例等方面的差异。结果 与普通模式相比,协作小组模式下,参与治疗的专业人数增加、住ICU天数、ICU治疗费用和住院总费用下降,血液滤过总时间延长、住院期间入液总量减少和药物占住院费用比例降低。结论 协作小组是基层医院重症医学科运行的好模式,值得进一步完善。  相似文献   
64.
Little is known about the identities and functions of extracellular signaling molecules that work in concert with neuronal activity to regulate refinement and maintenance of the mouse olfactory sensory map. We show that expression of a dominant negative retinoic acid receptor (RAR) in olfactory sensory neurons (OSNs) increased the number of glomeruli that incorrectly contained OSN axons expressing different odorant receptors. This phenotype became apparent postnatally, coincided with increased cell death, and was preceded by increased Neuropilin-1 and reduced Kirrel-2 expressions. Kirrel-2-mediated cell adhesion influences odorant receptor-specific axonal convergence and is regulated by odorant receptor signaling via the olfactory cyclic nucleotide-gated (CNG) ion channel. Accordingly, we found that inhibited RAR function correlated with reduced CNG channel expression. Naris occlusion experiments and analysis of CNG channel-deficient mice further indicated that RAR-regulated CNG channel levels influenced the intrinsic neuronal activity required for cell survival in the absence of odor stimulation. Finally, we showed that CNG channel activity regulated expression of the retinoic acid-degrading enzyme Cyp26B1. Combined, these results identify a novel homeostatic feedback mechanism involving retinoic acid metabolism and CNG channel activity, which influences glomerular homogeneity and maintenance of precisely connected OSNs.  相似文献   
65.
Human organic cation transporter 2 (hOCT2) is involved in transport of many endogenous and exogenous organic cations, mainly in kidney and brain cells. Because the quaternary structure of transmembrane proteins plays an essential role for their cellular trafficking and function, we investigated whether hOCT2 forms oligomeric complexes, and if so, which part of the transporter is involved in the oligomerization. A yeast 2-hybrid mating-based split-ubiquitin system (mbSUS), fluorescence resonance energy transfer, Western blot analysis, cross-linking experiments, immunofluorescence, and uptake measurements of the fluorescent organic cation 4-(4-(dimethylamino)styryl)-N-methylpyridinium were applied to human embryonic kidney 293 (HEK293) cells transfected with hOCT2 and partly also to freshly isolated human proximal tubules. The role of cysteines for oligomerization and trafficking of the transporter to the plasma membranes was investigated in cysteine mutants of hOCT2. hOCT2 formed oligomers both in the HEK293 expression system and in native human kidneys. The cysteines of the large extracellular loop are important to enable correct folding, oligomeric assembly, and plasma membrane insertion of hOCT2. Mutation of the first and the last cysteines of the loop at positions 51 and 143 abolished oligomer formation. Thus, the cysteines of the extracellular loop are important for correct trafficking of the transporter to the plasma membrane and for its oligomerization.  相似文献   
66.
In most mammals the growth hormone (GH) locus comprises a single gene expressed primarily in the anterior pituitary gland. However, in higher primates multiple duplications of the GH gene gave rise to a complex locus containing several genes. In man this locus comprises five genes, including GH-N (expressed in pituitary) and four genes expressed in the placenta, but in other species the number and organization of these genes vary. The situation in chimpanzee has been unclear, with suggestions of up to seven GH-like genes. We have re-examined the GH locus in chimpanzee and have deduced the complete sequence. The locus includes five genes apparently organized in a fashion similar to that in human, with two of these genes encoding GH-like proteins, and three encoding chorionic somatomammotropins/placental lactogens (CSHs/PLs). There are notable differences between the human and chimpanzee loci with regard to the expressed proteins, gene regulation, and gene conversion events. In particular, one human gene (hCSH-L) has changed substantially since the chimpanzee/human split, potentially becoming a pseudogene, while the corresponding chimpanzee gene (CSH-A1) has been conserved, giving a product almost identical to the adjacent CSH-A2. Chimpanzee appears to produce two CSHs, with potentially differing biological properties, whereas human produces a single CSH. The pattern of gene conversion in human has been quite different from that in chimpanzee. The region around the GH-N gene in chimpanzee is remarkably polymorphic, unlike the corresponding region in human. The results shed new light on the complex evolution of the GH locus in higher primates.  相似文献   
67.
The dry extract of Hedra helix leaves and its main active compounds, predominantly α-hederin and hederacoside C, has been traditionally believed to act spasmolytic. However, it has been recently proved that both, the extract of ivy and triterpenoid saponins, exhibit strong contractile effect on rat isolated stomach smooth muscle strips. It turned out that the most potent contractile agent isolated from the extract of ivy leaves is α-hederin. Thus, it seems reasonable to estimate the mechanism of the contractile effect of this saponin. The presented study was aimed at verifying the participation of cholinergic pathways (muscarinic and nicotine receptors) in α-hederin-induced contraction. The experiments were carried out on rat isolated stomach corpus and fundus strips under isotonic conditions. The preparations were preincubated with either atropine or hexamethonium and then exposed to α-hederin. All results are expressed as the percentage of the response to acetylcholine - a reference contractile agent. The obtained results revealed that the pretreatment of isolated stomach strips (corpus and fundus) with atropine neither prevented nor remarkably reduced the reaction of the preparations to α-hederin. Similarly, if the application of saponin was preceded by the administration of hexamethonium, the strength of the contraction of stomach fundus strips induced by α-hederin was not modified. Concluding, it can be assumed that the cholinergic pathways do not participate in α-hederin-evoked contraction of rat isolated stomach preparations.  相似文献   
68.
We evaluated the antimicrobial activity and some mechanisms used by subinhibitory and inhibitory concentrations of the essential oil, obtained from leaves of Plectranthus amboinicus, against a standard strain of Klebsiella pneumoniae and 5 multiresistant clinical isolates of the bacteria. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC), the rate of kill and the pH sensitivity of the essential oil were determined by microdilution tests performed in 96-well plates. Subinhibitory and inhibitory concentrations of the essential oil were tested in order to check its action on K. pneumoniae membrane permeability, capsule expression, urease activity and cell morphology. The MIC and MBC of the essential oil were 0.09±0.01%. A complete inhibition of the bacterial growth was observed after 2h of incubation with twice the MIC of the essential oil. A better MIC was found when neutral or alkaline pH broth was used. Alteration in membrane permeability was found by the increase of crystal violet uptake when the bacteria were incubated with twice the MIC levels of the essential oil. The urease activity could be prevented when all the subinhibitory concentrations were tested in comparison to the untreated group (p<0.001). Alteration of the bacterial morphology besides inhibition of the capsule expression was verified by atomic force microscopy, and Anthony's stain method, respectively. Our data allow us to conclude that the essential oil of P. amboinicus can be a good candidate for future research.  相似文献   
69.
70.
This review gives an overview on the analysis of inorganic nickel species and their toxic effects. Based on the analytical procedure applied inorganic nickel species are usually classified in soluble, sulfidic, metallic and oxidic nickel fractions. Only few works were attempting a chemical characterization of the different nickel compounds in each fraction. This general classification in four nickel species groups is widely used in toxicological studies dealing with nickel particulate matter in workplace air. Compared to the general population, occupationally exposed people have a higher risk of respiratory tract cancer due to inhalation of nickel at their workplace in the nickel-producing or using industries. High cancer risk is related to less soluble oxidic and especially sulfidic nickel species in refinery dust. In contrast, within the general population the most harmful health effect related to nickel exposure is allergic contact dermatitis due to prolonged skin contact with nickel. Absorption processes of nickel species and molecular mechanisms of nickel toxicity are briefly outlined.  相似文献   
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