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61.

Objectives  

Several investigators have reported that clinical improvements of patients with rheumatoid arthritis (RA), from participating in therapeutic diet intervention studies, have been accompanied by loss of body weight. This has raised the question whether weight reduction per se can improve RA. In order to test this hypothesis, three previously conducted diet intervention studies, comprising 95 patients with RA, were pooled. Together with Age, Gender, and Disease Duration, change during the test period in body weight, characterised dichotomously as reduction or no reduction (dichoΔBody Weight), as well as Diet (dichotomously as ordinary diet or test diet), were the independent variables. Dependent variables were the difference (Δ) from baseline to conclusion of the study in five different disease outcome measures. ΔESR and ΔPain Score were both characterised numerically and dichotomously (improvement or no improvement). ΔAcute Phase Response, ΔPhysical Function, and ΔTender Joint Count were characterised dichotomously only. Multiple logistic regression was used to analyse associations between the independent and the disease outcome variables.  相似文献   
62.
Microcystins (cyclic heptapeptides) are produced by a number of freshwater cyanobacteria and cause concern in potable water supplies due to their acute and chronic toxicity. The present study reports the structural characterization of the degradation products of the photocatalytic oxidation of microcystin-LR, so aiding the mechanistic understanding of this process. TiO2 photocatalysis is a promising technology for removal of these toxins from drinking water. However, before it can be adopted in any practical application it is necessary to have a sufficient knowledge of degradation byproducts and their potential toxicity. Liquid chromatography-mass spectrometry analysis demonstrated that the major destruction pathway of microcystin appears to be initiated via three mechanisms: UV irradiation, hydroxyl radical attack, and oxidation. UV irradiation caused geometrical isomerization of microcystin converting the (4E), (6E) of the Adda configuration to (4E), 6(Z) or 4(Z), 6(E). Hydroxyl radical attack on the conjugated diene structure of Adda moiety produced dihyroxylated products. Further oxidation cleaved the hydroxylated 4-5 and/or 6-7 bond of Adda to form aldehyde or ketone peptide residues, which then were oxidized into the corresponding carboxylic acids. Photocatalysis also hydrolyzed the peptide bond on the ring structure of microcystin to form linear structures although this appeared to be a minor pathway.  相似文献   
63.
Non-carcinogenic effects of TCDD in animals   总被引:20,自引:0,他引:20  
Exposure to TCDD and related chemicals leads to a plethora of effects in multiple species, tissues, and stages of development. Responses range from relatively simple biochemical alterations through overtly toxic responses, including lethality. The spectrum of effects shows some species variability, but many effects are seen in multiple wildlife, domestic, and laboratory species, ranging from fish through birds and mammals. The same responses can be generated regardless of the route of exposure, although the administered dose may vary. The body burden appears to be the most appropriate dosimetric. Many of the effects often attributed to TCDD are associated with relatively high doses: lethality, wasting, lymphoid and gonadal atrophy, chloracne, hepatotoxicity, adult neurotoxicity, and cardiotoxicity. Changes in multiple endocrine and growth factor sytems have been reported in a manner which is tissue, sex, and age-dependent. The most sensitive adverse effects observed in multiple species appear to be developmental, including effects on the developing immune, nervous, and reproductive systems. Such effects have been observed at maternal body burdens in the range of 30-80 ng/kg in both non-human primates and rodents. Biochemical effects on cytokine expression and metabolizing enzymes occur at body burdens which are within a factor of ten of the clearly adverse developmental responses. Thus, effects on the immune system, learning, and the developing reproductive system of multiple animals occur at body burdens which are close to those present in the background human population.  相似文献   
64.
Sudden release of platelet-activating factor (PAF) into the circulation can cause hypotension, tachycardia, and circulatory collapse. To further examine this response, we performed detailed studies of cardiovascular function after PAF administration to young domestic pigs and newborn piglets. Our results indicate that circulatory dysfunction after PAF reflects severe constriction of pulmonary resistance vessels and consequent acute right ventricular failure. Although PAF-induced coronary artery constriction and contractile depression may be complicating problems, left ventricular underperfusion and dysfunction after PAF are mainly the result of systemic arterial hypotension and diminished left ventricular filling. The adverse hemodynamic effects of PAF are accompanied by substantial release of thromboxane A2 (TxA2). These effects are mimicked by the TxA2 agonist U-46619 and partially blocked by specific and nonspecific inhibitors of TxA2 synthesis (OKY-046 and indomethacin). Even more potent blockade of PAF action is exerted by the TxA2 receptor blocker, SQ 29,548. Taken together, these findings indicate that severe pulmonary vascular constriction and hemodynamic collapse soon after intravenous PAF are at least partially mediated by PAF-induced TxA2 release. Tachyphylaxis to PAF influence has been observed in studies of leukocyte and platelet function. We hypothesized that tachyphylaxis to PAF might also occur in our studies of constrictor responses in pulmonary vessels. Recently, we have examined the capacity of PAF to produce sustained pulmonary vasoconstriction in openchested, anesthetized newborn piglets. Infusions sufficient to produce 100% increase in mean pulmonary artery pressure after 3 min showed no loss of efficacy when sustained for 30 min. The same was true for infusions of U-46619. Thus, the pulmonary vasoconstrictor influence of PAF or U-46619 is not readily diminished by tachyphylaxis. These findings favor the viewpoint that PAF or TxA2 release during inflammatory processes could have prolonged adverse actions on pulmonary and systemic circulations. Based on a paper presented at the Third International Conference on Platelet-Activating Factor and Structurally Related Alkyl Ether Lipids, Tokyo, Japan, May 1989. The opinions or assertions contained here are those of the authors. They do not reflect the views of the Department of Defense or the Uniformed Services University of the Health Sciences. The experiments reported here were conducted according to the principles set forth in the “Guide for the Care and Use of Laboratory Animals,” Institute of Laboratory Animal Resources, U.S. Department of Health and Human Services (NIH Publ. 85-23, 1985).  相似文献   
65.
Compared a total of 159 male Long-Evans rat pups and adults on their ability to learn taste aversions with 1- and 2-bottle tests, 2 different illness-inducing agents and flavors, and varying taste–illness delays. Rat pups learned taste aversions with either 1- or 2-bottle tests, but only with short taste–illness delays. Delays of 60 min were sufficient to block taste aversion learning in pups. Pups also failed to demonstrate neophobia to a novel taste. These findings suggest that pups forget taste information more rapidly than adults, perhaps because taste information is not so salient for pups as for adults. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
66.
Reports an error in the original article by D. H. Crowell et al (Developmental Psychology, 1976[Jul], 12(4), 373-397). Corrections to equations 1, 2, and 3 on pages 381 and 382 are presented. (The following abstract of the original article appeared in record 1976-20687-001.) Three experiments demonstrated that human newborn heart rate level can be reliably modified through classical conditioning procedures. The theory of sensitization served as a frame of reference for Exps I and II, and drive reduction served for Exp III. In Exp I the delay, delay-trace, and control groups, with 10 2-day-old newborns in each, received 5 preconditioning trials of the CS alone, 16 conditioning trials with CS-UCS pairings differing for each group, and 5 extinction trials. Exp II was a replication of the 1st study and involved only the delay and delay-trace groups with 10 infants each. In both studies the delay group curves showed significant monophasic acceleratory responses during extinction. Results support the sensitization hypothesis (i.e., the CR occurring in the interstimulus interval was fashioned out of the response to the CS). In Exp III, the measure of conditioning was the response to the probe technique. 10 experimental Ss received preconditioning trials of nitrogen puff (UCS-sub-1) administered to the abdomen, followed by 10 CS-UCS-sub-2 (500-Hz tone acetic acid) pairings with an interstimulus interval of 3 sec. 10 controls received the same design with a CS-UCS-sub-2 interval of 40 sec. Analyses of the probe stimulus trials showed significant changes for the control group and none for the experimental group. The CS-UCS-sub-2 pairings in the experimental group are interpreted as producing increased drive and adaptive damping of the heart rate response. Findings show that early learning may occur under a variety of conditions and that the results can be incorporated by different theories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
67.
    
Disaster response requires the cooperation of multiple emergency responder organizations (EROs). However, after‐action reports relating to large‐scale disasters identity communication difficulties among EROs as a major hindrance to collaboration. On the one hand, the use of two‐radio communication, based on multiple orthogonal frequencies and uneven coverage, has been shown to degrade inter‐organization communication. On the other hand, because they reflect different areas of expertise, EROs use differing terminologies, which are difficult to reconcile. These issues lead to ambiguities, misunderstandings, and inefficient exchange of data and information among those involved, which can impede the response process and slow decision making. We, therefore, hypothesize that promoting semantic interoperability across ERO information systems might improve information exchange among stakeholders and thereby allow a more coherent response to the disaster. We propose an ontology‐based messaging service on the basis of the Emergency Data Exchange Language (EDXL) standards. The parties involved will continue to use the terminologies to which they are accustomed, but the system will resolve inconsistencies and thereby enhance mutual understanding among EROs by ensuring semantic translation of the exchanged information. The evaluation of the semantic translation demonstrated the effectiveness and accuracy of the proposed service.  相似文献   
68.

Purpose  

To investigate a wavelet-based filtering scheme for denoising of arterial spin labeling (ASL) data, potentially enabling reduction of the required number of averages and the acquisition time.  相似文献   
69.
    
Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS.  相似文献   
70.
    
Simple SummaryDiabetic nephropathy is one of the most frequent complications of diabetes, resulting from diffuse damage to different kidney cells. The identification of subjects at risk is mandatory to prevent its development and provide appropriate therapies reducing the unmanageable evolution towards end-stage kidney disease. The aim of this work was to identify urinary-derived extracellular vesicles (EVs) miRNA cargo to be used as biomarker of kidney damage in diabetic patients. The miRNA profile was then correlated with the molecular mechanism associated with the glomerular and tubular damage using a diabetic-like model. In patients, miR145 and miR126 in urinary EVs increased together with albuminuria. MiR145 and miR126 increased in parallel in EVs from renal epithelial cells undergoing transition to a fibrotic mesenchymal phenotype. These data unveiled a role for miR126 and miR145 as the biomarkers of damage progression and proteinuria development in diabetic nephropathy. AbstractDiabetic nephropathy (DN) is a severe kidney-related complication of type 1 and type 2 diabetes and the most frequent cause of end-stage kidney disease. Extracellular vesicles (EVs) present in the urine mainly derive from the cells of the nephron, thus representing an interesting tool mirroring the kidney’s physiological state. In search of the biomarkers of disease progression, we here assessed a panel of urinary EV miRNAs previously related to DN in type 2 diabetic patients stratified based on proteinuria levels. We found that during DN progression, miR145 and miR126 specifically increased in urinary EVs from diabetic patients together with albuminuria. In vitro, miRNA modulation was assessed in a model of TGF-β1-induced glomerular damage within a three-dimensional perfusion system, as well as in a model of tubular damage induced by albumin and glucose overload. Both renal tubular cells and podocytes undergoing epithelial to mesenchymal transition released EVs containing increased miR145 and miR126 levels. At the same time, miR126 levels were reduced in EVs released by glomerular endothelial cells. This work highlights a modulation of miR126 and miR145 during the progression of kidney damage in diabetes as biomarkers of epithelial to mesenchymal transition.  相似文献   
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