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Currently available anti-inflammatory drugs for the treatment of multiple sclerosis (MS) and other inflammatory diseases are generally inadequate, with disease progression not being arrested by the treatments and undesirable side effects posing problems. In response to these deficiencies our laboratories have, over the past 10 years, been developing novel drugs that interfere with the entry of leucocytes into inflammatory sites by inhibiting their passage through the subendothelial basement membrane (BM). This review initially summarizes evidence supporting the hypothesis that the subendothelial BM is a major barrier to the accumulation of leucocytes in inflammatory sites. An important point that has emerged is that breaching of the BM is probably a cooperative process, involving activation- and cytokine-induced degradative enzymes contributed by leucocytes, endothelial cells and platelets. The review then discusses the properties of three separate classes of anti-inflammatory compounds we have developed, namely sulfated polysaccharides/oligosaccharides, phosphosugars, and castanospermine (CS), which inhibit the passage of leukocytes through BM. Each drug type appears to prevent BM degradation by a different mechanism. Sulfated polysaccharides/oligosaccharides mediate their anti-inflammatory effect by inhibiting the endoglycosidase, heparanase, which plays a key role in the solubilization of BM by invading leucocytes. In fact, our studies have highlighted the heparanase enzyme as a major target for future drug development. Phosphosugars probably inhibit inflammation by displacing lysosomal enzymes, which are involved in BM degradation, from cell surface mannose 6-phosphate receptors. This mechanism of expressing degradative enzymes on the cell surface is particularly evident with activated T lymphocytes. On the other hand, CS interferes with appropriate targeting of lysosomal enzymes involved in BM degradation. For reasons which are still unclear, CS specifically inhibits BM degradation by endothelial cells, which results in a characteristic perivascular arrest of leucocytes in inflammatory sites. Overall, our studies have established that inhibitors of subendothelial BM degradation represent viable anti-inflammatory agents. It is hoped that future work will result in the development of a totally new class of highly effective, subtle and non-toxic anti-inflammatory drugs for the treatment of MS and other inflammatory diseases.  相似文献   

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BACKGROUND: The scope of self-medication is increasing in many countries, and drugs for dyspepsia are a popular group for deregulative activities. This study investigated what kind of upper gastrointestinal symptoms people self-medicate and how appropriate this self-medication is. METHODS: An anonymous questionnaire was give to 50 consecutive customers buying antacids, alginates, or sucralfates in 10 pharmacies in the capital area in Finland in 1995. In half of the pharmacies the questionnaire was returned by mail, and in the other half the questionnaire was filled out at the pharmacy. The response rate was 53% (n = 292). RESULTS: The commonest reasons for self-medication were heartburn (88%), gastrointestinal pain (31%), and acid regurgitation (32%). Seventy-five per cent of respondents had used dyspepsia drugs for more than a year. The commonest way to self-medicate was to interchange regular and occasional use. Knowledge about the proper use of dyspepsia drugs was poor, and 6% of respondents had symptoms contraindicating self-medication but had not visited a physician during the past year. Patients more than 60 years old were especially at risk of potential inappropriate use. CONCLUSIONS: Over-the-counter (OTC) drugs for dyspepsia are likely to be used improperly. A physician's advice on the use of OTC dyspepsia drugs, in addition to detailed printed information about drug action and proper administration, would be important means to guarantee appropriate use of these drugs.  相似文献   

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The Ways of Coping Questionnaire (WCQ) is the most widely used measure of basic coping responses. In Study 1, 6 different theoretical models corresponding to the various dimensions of coping as assessed by the WCQ were tested for goodness of fit using confirmatory factor analysis. 530 college students completed the WCQ before a midterm exam, and their responses were the basis of the analysis. None of the coping models were good representations of the data. Study 2 aimed to derive a replicable set of coping dimensions using a series of exploratory factor analyses with the data collected in Study 1. A 4-factor model was derived and subsequently tested for its goodness of fit with another sample of 392 college students who were also preparing for a midterm exam. This 4-factor model also proved to be a poor representation of the data. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

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BACKGROUND: Lactic acidosis, generally defined as a plasma lactate concentration in excess of 5 mmol/L with a concomitant blood pH less than 7.25, is reported to have a direct association with mortality. OBJECTIVE: To report a case of unexplained perioperative lactic acidosis and to discuss the etiology, recognition, treatment, and importance of a transient rise in plasma lactate concentration. SUMMARY: Severe lactic acidosis developed in a 40-year-old man with Crohn's disease during major abdominal surgery. The plasma lactate concentration reached 16.9 mmol/L (normal range 1.5 to 2.2 mmol/L). This condition resolved within 14 hours without harm to the patient. CONCLUSIONS: When lactate accumulates in the perioperative period, the responsible condition is most often self-limiting. Reversible, subacute, marked lactic acidosis should not be assumed to predict mortality as it does in patients whose plasma lactate concentrations remain chronically elevated during severe systemic diseases such as sepsis.  相似文献   

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This commentary on the special section on clinical adolescent psychology (G. Holmbeck & P. Kendall, 2002) reviews and critiques the conceptual and empirical articles that this compilation comprises. As articulated in the conceptual contributions to this collection, two fundamental principles should guide research on the etiology, prevention, and treatment of psychological disorder and dysfunction during adolescence: First, drawing on the field of developmental psychopathology, the study of clinical adolescent psychology should focus on the trajectories of disorder that precede, characterize, and follow adolescence. Second, drawing on the literature on normative adolescent development, the study of clinical adolescent psychology must proceed with an explicit recognition of the unique biological, cognitive, psychosocial, and contextual features that define adolescence as a developmental period. Although the study of clinical adolescent psychology, as evidenced by this collection of articles, is appropriately grounded in the broader enterprise of developmental psychopathology, less progress has been made with respect to die integration of the study of clinical phenomena in adolescence with the study of normative adolescent development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

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While much has been written about the value of clinical supervision and theoretical models of how it should take place, few accounts exist of how it works in practice. This paper illustrates how supervision was implemented within a directorate in one trust. Both pitfalls and successes of the project are highlighted together with a summary of the evaluation. Evaluation demonstrated that two-thirds of those receiving supervision valued it highly.  相似文献   

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Jerry M. Burger's (see record 2008-19206-001) partial replication of Stanley Milgram's (1974) obedience study shows both the influence of culture and generations on behavior and the power of the situation. In Burger's data, disobedience has nearly doubled among male participants since the 1960s, a shift just as large as the increase in Americans' body mass index that has been labeled the obesity epidemic. Differences in the ethnic composition of the two studies' samples, particularly the large numbers of Asian Americans in Burger's sample, may have suppressed what might have been an even larger increase in disobedience. Halting the experiment at 150 volts may also have suppressed change. Nevertheless, situations have a strong influence on behavior; thus generational shifts would not be expected to completely eliminate the effect. Burger's results are consistent with documented changes in personality traits over the generations, including increases in nonconformist traits such as assertiveness, self-esteem, and narcissism. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

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Discusses lessons that the authors' experiences in the area of service quality have taught them about how to help a business develop into the kind of company that can deliver quality service to its customers. A theme running through the article is that becoming such a company is a multistage process that involves coordinating changes in many facets of organizational functioning. Furthermore, it is repeatedly emphasized that the design of these facets must be aligned with the market sector the organization wants to target. Lessons 1, 2, and 3 address the implications of service marketing, operations management, and human resources management for delivering quality service. The integration of what has been learned in these 1st 3 lessons is the topic of Lesson 4: creating a climate and a culture for service. Finally, some practical suggestions and guidelines are offered for beginning the process of becoming a service organization. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

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As indicated by an Fe(II)-induced liposome peroxidation bioassay, the EtOAc extract of tart cherries (Prunus cerasus) was found to have strong antioxidant activity. Purification of this extract afforded chlorogenic acid methyl ester (1) and three novel compounds, 2-hydroxy-3-(o-hydroxyphenyl) propanoic acid (2); 1-(3', 4'-dihydroxycinnamoyl)-cyclopenta-2,5-diol (3), and 1-(3', 4'-dihydroxycinnamoyl)-cyclopenta-2,3-diol (4), as determined by their spectral data. At a 20-microM concentration, the antioxidant activities of compounds 3 and 4 were comparable to the antioxidant activities of caffeic acid, whereas compound 1 showed activity similar to chlorogenic acid. Also, these compounds showed antioxidant activities similar to the commercial antioxidants tert-butylhydroquinone and butylated hydroxytoluene. However, compound 2 was not active when tested at a 100-microM concentration.  相似文献   

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Release of the Rashkind ductus umbrella may be complicated in that the central wire of the delivery catheter may become trapped within the foam of the umbrella. This problem occurs only if the central retaining wire is advanced when trying to disengage the catheter and umbrella. We propose a simple solution to the problem: Retract the sleeve instead of advancing the retaining wire.  相似文献   

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