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Exposure of the rat to restraint results in activation of the hypothalamic-pituitary-adrenal (HPA) axis, a characteristic pattern of c-fos expression in the brain and increased cardiovascular function. These responses adapt with repeated exposure of an individual to the same stress. Corticosterone secretion habituates, and c-fos mRNA expression in the paraventricular nucleus of the hypothalamus (PVN) decreases. The increased expression of corticotropin releasing hormone mRNA in the PVN also becomes less prominent, whereas vasopressin mRNA progressively increases. The neural mechanisms responsible for this adaptation remain obscure. Because of its role in conditioned learning, we have hypothesised that the amygdala might be involved in this adaptive process. Here we show that large neurotoxic lesions of the amygdala in male rats do not prevent acute stress activation of the HPA axis following 30 min restraint, whilst more discrete lesions of the central nucleus actually exacerbate the acute response. Rats with large amygdala lesions demonstrate delayed habituation of corticosterone and c-fos to repeated restraint, an affect not apparent with central nucleus lesions. Furthermore we show that neither type of lesion significantly reduced tachycardiac responses to single or repeated restraint as measured by telemetry. We conclude that the amygdala and the central nucleus are not necessary for HPA and cardiovascular activation in response to stress (though the central nucleus may modulate it), and that adaptation to repeated stress is only modestly dependent upon the amygdala. 相似文献
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Does an ultra violet photooxidation of the manganese-loaded/copper-depleted prion protein in the retina initiate the pathogenesis of TSE? 总被引:1,自引:0,他引:1
M Purdey 《Medical hypotheses》2001,57(1):29-45
Ecosystems supporting clusters of sporadic transmissible spongiform encephalopathy (TSE) are characterized by common properties of high-manganese/low-copper, zinc, selenium mineral status, and high-altitude/snow-covered/pre-cambrian mountain terrain where above-average intensities of ultra violet/ozone oxidants are prevalent. Cell culture trials have confirmed the hypothesis that manganese (Mn) substitutes at Prion Protein’s (PrP’s) vacated copper (Cu) domain, whereupon PrP loses its Cu-mediated antioxidant function, transforming into a protease-resistant misfolded isoform that aggregates into fibril ‘tombstone’ structures – the key hallmark distinguishing TSE central nervous system (CNS) pathology. The cellular localisation of PrP suggests PrP serves a ‘front line’ contributory role in neutralizing radicals generated by incoming environmental oxidants, whilst an intensive expression of PrP messenger ribonucleic acid (mRNA) in the retina, melanocytes, epidermis, etc., suggests PrP performs a key antioxidant role as a ‘photooxidative shock absorber’; binding of porphyrin IX, Congo red and other photosensitisers to PrPc suggests PrPc serves as an integral associate of the porphyrin/melanin chromophore electron transfer chain; thereby serving as a quencher of singlet O2/superoxide generated by photoenergised chromophores/xeno photosensitisers. It is proposed that sporadic TSE pathogenesis is initiated in the retina of environmentally/genetically predisposed individuals via a two-stage chronic toxic process – Mn substitution at PrP’s Cu domain forming a stable Mn2+-PrP complex, followed by an ultra violet in situ photo-oxidization of the Mn2+ component; whereby the latent ‘Jekyll and Hyde’ capacity of the Mn2+-PrP conjugate is activated into the fully fledged, ‘infectious’ lethal auto-oxidizing, Mn3+-PrP ‘prion’ agent. Thus, PrPc’s Cu-mediated antioxidant function is replaced by a Mn3+-mediated autooxidant dysfunction. Could the UK’s increased loading of a cocktail of environmental oxidants that penetrated the CNS of the UK bovine (ultra violet microwaves/ozone/systemic cu-chelating insecticides) account for a more virulent Mn4+ mediated acceleration of the TSE degenerative process in Mn-contaminated/genetically predisposed individuals, manifesting as the widespread emergence of new-variant bovine spongiform encephalopathy (BSE)/variant Creutzfeldt–Jacob disease (VCJD)/FSE in younger mammals? 相似文献
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Pearl-Yafe M Iskovich S Kaminitz A Stein J Yaniv I Askenasy N 《Autoimmunity reviews》2006,5(5):338-343
The initial immune process that triggers autoimmune beta cell destruction in type 1 diabetes is not fully understood. In early infancy there is an increased beta cell turnover. Recurrent exposure of tissue-specific antigens could lead to primary sensitization of immune cells in the draining lymph nodes of the pancreas. An initial immune injury to the beta cells can be inflicted by several cell types, primarily macrophages and T cells. Subsequently, infiltrating macrophages transfer antigens exposed by apoptotic beta cells to the draining lymph nodes, where antigen presenting cells process and amplify a secondary immune reaction. Antigen presenting cells evolve as dual players in the activation and suppression of the autoimmune reaction in the draining lymph nodes. We propose a scenario where destructive insulitis is caused by recurrent exposure of specific antigens due to the physiological turnover of beta cells. This sensitization initiates the evolution of reactive clones that remain silent in the regional lymph nodes, where they succeed to evade regulatory clonal deletion. 相似文献
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Lavietes MH Natelson BH Cordero DL Ellis SP Tapp WN 《International journal of behavioral medicine》1996,3(1):70-83
Because the symptoms of acute hyperventilation (e.g., fatigue, headaches) and the complaints of patients with chronic fatigue syndrome (CFS) are similar, a relation may exist beiween these conditions. This study attempted to identify whether patients with CFS hyperventilate while breathing quietly or under stress. Two participant groups were compared: One comprised 10 patienls who met the established criteria for CFS; the other comprised 9 control participants matched to patients with respect to age, sex, and socioeconomic status. Participants sat and breathed quietly through a mouthpiece for the entire study. Minute ventilation (Vc), end-tidal CO2 (Pc1CO2), and heart rale were monitored before, during, and after presentation of psychosocial and chemical (inspiration of 5% C02 + 95% 02) stressors. Two psychological stressors were used: a computational and a socioevalualive task. To evaluate each patient’s perception of dyspnea, a modified Borg scale questionnaire was administered, All the variables measured except Pc,CO2; were similar in patients and normals before stressors; PcCO2 of participants was significantly less than controls (p > .025). Vc, Borg scores, and PcCO2 were not altered by psychological stress; respiratory rate did increase significantly during stress but only for the control group, In contrast, increases in heart rate occurred more consistently in the patient group than in controls, Ventilatory output did not differ between groups during CO2 stimulation. These data show that patients with CFS arc hypocapnic at rest. We define normal ventilation as eucapnia; therefore, patients with CFS hyperventilate. However, because Vr during tidal hrealhing as well as the ventilatory responses to both CO2 and (lab stressors were similar in patients and controls, the reason for hyperventilation is unclear. 相似文献
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BACKGROUND: The aim of the study was to investigate the effect of psychological stress before and during IVF treatment on the outcome of IVF, controlling for known physiological predictors. METHODS: This is a prospective, longitudinal study. A total of 166 women were studied during their first IVF treatment. They answered questionnaires concerning psychological and social factors on two occasions. Psychological well-being was measured by the Psychological General Well-Being (PGWB) index and psychological effects of infertility were assessed by 14 items. RESULTS: In the analysis of the psychological variables, no differences were found between pregnant and non-pregnant women. The total number of good quality embryos, the number of good quality embryos transferred, and the number of embryos transferred were significantly higher in the pregnant than in the non-pregnant group. In a multivariate analysis, the number of good quality embryos transferred was the only variable that was independently associated with pregnancy. CONCLUSIONS: We found no evidence that psychological stress had any influence on the outcome of IVF treatment. When counselling infertile couples, it might be possible to reduce the stress they experience during the treatment procedure by informing them of these findings. 相似文献
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Lehtonen ST Ohlmeier S Kaarteenaho-Wiik R Harju T Pääkkö P Soini Y Kinnula VL 《Antioxidants & redox signaling》2008,10(4):813-819
The thioredoxin/peroxiredoxin system comprises a redox-regulated antioxidant family in human lung; its significance, regulation, or oxidation has not been evaluated in smoking-related lung diseases. Here, we present the expression of the thioredoxin/peroxiredoxin system in lung biopsies from normal lung (n = 14), smokers (n = 21), and patients with chronic obstructive pulmonary disease (COPD, n = 38), and assess the possible inactivation/oxidation of this system by nonreducing Western blotting, two-dimensional gel electrophoresis, and mass spectrometry. Our study shows that the thiol status of the Trx/Prx-system can be modulated in vitro, but it appears to have high resistance against the oxidative stress in COPD. 相似文献
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Stüve-Wiedemann syndrome (SWS) is a severe congenital skeletal dysplasia associated with life threatening dysautonomic manifestations. Newborns affected with this condition exhibit distinctive shortening and bowing of the long bones with reduced bone volume. The majority of affected newborns die early due to neuromuscular complications namely hyperthermia, apnea, and swallowing difficulties. In this review, we provide an overall picture on the clinical, including long-term management, molecular and cellular aspects of SWS and discuss briefly other related bent bone dysplasias. 相似文献
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Sagittal fractures of the first phalanx are a common, potentially catastrophic injury in racehorses. These fractures are often linked to an acute, one time, biomechanical event; however, recent evidence implies that chronic exposure to stress can lead to the accumulation of bony changes that affect the structural integrity of the bone and increase the likelihood of fracture. The aim of the study was to compare variations of two common metrics of bone adaptation – subchondral bone density and thickness across the proximal articular surface of the first phalanx in Thoroughbred horses that (1) raced but never experienced a first phalanx fracture (Raced Control); (2) raced and had experienced fracture of the contralateral first phalanx (Contralateral to Fracture); (3) had never raced or experienced a first phalanx fracture (Unraced Control). A total of 22 first phalangeal bones were sampled post‐mortem and imaged using micro‐computed tomography calibrated for mineral density measures. Measurements of volumetric subchondral bone mineral density and thickness were taken from images at five sites from medial to lateral, in three coronal planes (25, 50 and 75% dorsal‐palmar). At each of the 15 sites, measurements were repeated and averaged across 10 adjacent micro‐computed tomography slices of bone, spanning 0.75 mm. The magnitude and variance of these measurements were compared between sites and between cohorts with non‐parametric statistical tests. Across the proximal osteochondral surface of the first phalanx, the pattern of subchondral bone volumetric bone mineral density and thickness varied with each coronal section studied. The subchondral bone thickness was greater for the central and dorsal coronal sections, compared with the palmar section. For the race‐fit groups (Raced Control and Contralateral to Fracture), the highest volumetric bone mineral density was in the central sagittal groove. The volumetric bone mineral density was significantly greater in the sagittal groove in the central coronal section in the raced than the unraced group. The Contralateral to Fracture group demonstrated significantly greater variance of volumetric bone mineral density compared with the Raced Control and Unraced Control (P < 0.0001), with no difference in variance noted between the Raced Control and Unraced Control groups. There was a small (R rank = 0.3) but significant correlation between subchondral bone volumetric bone mineral density and thickness in the Contralateral to Fracture group (P = 0.005). The findings demonstrate that differences exist in subchondral bone volumetric bone mineral density and thickness across the proximal osteochondral surface of the equine first phalanx in horses with different training histories. The findings also demonstrate that the subchondral bone of the sagittal groove of the equine first phalanx adapts to race‐training in the race‐fit groups (Raced Control and Contralateral to Fracture) with an increase in volumetric bone mineral density relative to unraced controls. Within the race‐trained groups, the Contralateral to Fracture bones had a greater variance of volumetric bone mineral density, suggesting that stress‐induced bone adaptation had become more erratic, potentially contributing to the aetiology of sagittal fractures of the first phalanx in the Thoroughbred racehorse. 相似文献
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The diagnosis of seronegative (SN-) antiphospholipid syndrome (APS) has been suggested for patients with clinical manifestations indicative of APS but with persistently negative results in the commonly used assays to detect anti-cardiolipin (aCL) antibodies, anti-β2 Glycoprotein I antibodies (aβ2GPI), and lupus anticoagulant (LA). To date the best management of these patients is still unclear. New emerging anti-phospholipid (aPL) assays could improve our ability in diagnosing APS. However, the availability of aPL assays in routine laboratory practice is limited. In fact, even aβ2GPI is routinely tested in only a small number of laboratories, and other aPL, such as anti-prothrombin or anti-annexin antibodies, in only a few research laboratories. On the other hand transient or false negative aPL assay and other genetic or acquired pro-thrombotic conditions can further complicate this issue. This paper is focused on the arguments for and against the diagnosis of SN-APS and is aimed to help the clinician when approaching a patient with clinical manifestations consistent with APS diagnosis but with negative aPL using the commonly available tests. 相似文献
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Purdey M 《Medical hypotheses》2003,60(6):797-820
Intensive exposures to natural and artificial sources of infrasonic acoustic shock (tectonic disturbances, supersonic aeroplanes, etc.) have been observed in ecosystems supporting mammalian populations that are blighted by clusters of traditional and new variant strains of transmissible spongiform encephalopathy (TSE). But TSEs will only emerge in those 'infrasound-rich' environments which are simultaneously influenced by eco-factors that induce a high manganese (Mn)/low copper (Cu)-zinc (Zn) ratio in brains of local mammalian populations. Since cellular prion protein (PrPc) is a cupro-protein expressed throughout the circadian mediated pathways of the body, it is proposed that PrP's Cu component performs a role in the conduction and distribution of endogenous electromagnetic energy; energy that has been transduced from incoming ultraviolet, acoustic, geomagnetic radiations. TSE pathogenesis is initiated once Mn substitutes at the vacant Cu domain on PrPc and forms a nonpathogenic, protease resistant, 'sleeping' prion. A second stage of pathogenesis comes into play once a low frequency wave of infrasonic shock metamorphoses the piezoelectric atomic structure of the Mn 3+ component of the prion, thereby 'priming' the sleeping prion into its fully fledged, pathogenic TSE isoform - where the paramagnetic status of the Mn 3+ atom is transformed into a stable ferrimagnetic lattice work, due to the strong electron-phonon coupling resulting from the dynamic 'Jahn-Teller' type distortions of the oxygen octahedra specific to the trivalent Mn species. The so called 'infectivity' of the prion is a misnomer and should be correctly defined as the contagious field inducing capacity of the ferrimagnetic Mn 3+ component of the prion; which remains pathogenic at all temperatures below the 'curie point'. A progressive domino-like 'metal to ligand to metal' ferrimagnetic corruption of the conduits of electromagnetic superexchange is initiated. The TSE diseased brain can be likened to a solar charged battery on continuous charge; where the Mn contaminated/Cu depleted circadian-auditory pathways absorb and pile up, rather than conduct the vital life force energies of incoming ultra violet, acoustic and geomagnetic radiation. Instead of harnessing these energies for the body's own bio-rhythmic requirements, an infrasonic shock induced metamorphosis of the Mn atom intervenes; initiating an explosive pathogenesis that perverts the healthy pathways of darkness and light; Cu prions are replaced by hyperpolarized Mn 3+ prions that seed self perpetuating 'cluster bombs' of free radical mediated neurodegeneration. TSE ensues. 相似文献
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Vera-Ramirez L Sanchez-Rovira P Ramirez-Tortosa MC Ramirez-Tortosa CL Granados-Principal S Fernandez-Navarro M Lorente JA Quiles JL 《Antioxidants & redox signaling》2011,15(4):903-909
Antineoplastic agents induce oxidative stress leading to lipid, carbohydrate, protein, and DNA damage. We sought to explore the role of drug-induced oxidative stress on breast cancer patient's survival. We observed that neoadjuvant patients presented a marked raise in DNA damage and protein carbonyl levels after chemotherapy, whereas postchemotherapy DNA repair activity of the KU86 enzyme and total antioxidant capacity of the plasma were higher in the adjuvant group. With respect to patient's survival, we observed that increasing levels of KU86 and antioxidant capacity of the plasma during chemotherapy significantly influenced the survival rates of the patients, protecting from disease recurrence and death. Our results suggest that chemotherapy induces a certain level of systemic oxidative stress, which is maintained along successive clinical interventions and could influence the clinical outcome of the patients. 相似文献
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Does skull morphology constrain bone ornamentation? A morphometric analysis in the Crocodylia
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F. Clarac T. Souter J. Cubo V. de Buffrnil C. Brochu R. Cornette 《Journal of anatomy》2016,229(2):292-301
Previous quantitative assessments of the crocodylians' dermal bone ornamentation (this ornamentation consists of pits and ridges) has shown that bone sculpture results in a gain in area that differs between anatomical regions: it tends to be higher on the skull table than on the snout. Therefore, a comparative phylogenetic analysis within 17 adult crocodylian specimens representative of the morphological diversity of the 24 extant species has been performed, in order to test if the gain in area due to ornamentation depends on the skull morphology, i.e. shape and size. Quantitative assessment of skull size and shape through geometric morphometrics, and of skull ornamentation through surface analyses, produced a dataset that was analyzed using phylogenetic least‐squares regression. The analyses reveal that none of the variables that quantify ornamentation, be they on the snout or the skull table, is correlated with the size of the specimens. Conversely, there is more disparity in the relationships between skull conformations (longirostrine vs. brevirostrine) and ornamentation. Indeed, both parameters GApit (i.e. pit depth and shape) and OArelat (i.e. relative area of the pit set) are negatively correlated with snout elongation, whereas none of the values quantifying ornamentation on the skull table is correlated with skull conformation. It can be concluded that bone sculpture on the snout is influenced by different developmental constrains than on the skull table and is sensible to differences in the local growth ‘context' (allometric processes) prevailing in distinct skull parts. Whatever the functional role of bone ornamentation on the skull, if any, it seems to be restricted to some anatomical regions at least for the longirostrine forms that tend to lose ornamentation on the snout. 相似文献
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Acharya B Chun SY Kim SY Moon C Shin HI Park EK 《Journal of biomedical materials research. Part B, Applied biomaterials》2012,100(3):841-849
Calcium phosphate ceramics have been widely used as scaffolds for bone regeneration. Here, to improve the osteogenic potential of hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) and to apply the bioactive peptide in situ, matrix extracellular phosphoglycoprotein (MEPE) peptide, which has been shown to stimulate osteoblast differentiation, was covalently and directionally immobilized on HA/β-TCP particles. The free-hydroxyl groups on the surface of the HA/β-TCP particles were sequentially conjugated with APTES, PEG-(SS)(2), and the synthetic MEPE peptide. Using FTIR and XPS, immobilization of the MEPE peptide on the HA/β-TCP was confirmed. Implantation of the MEPE peptide-immobilized HA/β-TCP into calvarial defect and subsequent analyses using a micro CT and histology showed significant bone regeneration and increased bone area (9.89-fold) as compared to that of unmodified HA/β-TCP. Moreover, tartrate-resistant acid phosphatase-positive osteoclasts were observed in regenerated bone by the MEPE peptide-immobilized HA/β-TCP, indicating that the bones newly formed by the MEPE peptide-immobilized HA/β-TCP are actively remodeled by osteoclasts. Therefore, our data demonstrate that MEPE peptide immobilization onto the HA/β-TCP surface stimulates bone regeneration associated with physiological bone remodeling. 相似文献
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Aspirin-induced asthma (AIA) is a distinct clinical syndrome characterized by severe asthma exacerbations after ingestion of aspirin or other non-steroidal anti-inflammatory drugs. The exact pathomechanism of AIA remains unknown, though ongoing research has shed some light. Recently, more and more attention has been focused on the role of aspirin in the induction of oxidative stress, especially in cancer cell systems. However, it has not excluded the similar action of aspirin in other inflammatory disorders such as asthma. Moreover, increased levels of 8-isoprostanes, reliable biomarkers of oxidative stress in expired breath condensate in steroid-naïve patients with AIA compared to AIA patients treated with steroids and healthy volunteers, has been observed. This review is an attempt to cover aspirin-induced oxidative stress action in AIA and to suggest a possible related pathomechanism. 相似文献