Aspirin resistance

Treatment failures occur with any drug and aspirin is no exception. Evidence is growing to indicate that there are subpopulations that do not respond to antithrombotic action of aspirin. The term 'aspirin resistance' has been used to describe a number of different phenomena, including inability of aspirin to: (i) protect against cardiovascular events despite its regular intake; (ii) to affect various laboratory tests, reflecting platelet activity. Research on aspirin resistance yielded interesting results in clinical pharmacology and pharmacogenetics. Future studies will show whether genotyping for polymorphisms might be of value in everyday clinical use of aspirin. Present data indicate that in survivors of recent myocardial infarction or unstable angina, patients receiving coronary artery bypass grafts, as well as in subjects with hypercholesterolemia, aspirin resistance has to be considered when implementing antithrombotic therapy. However, in individual patients the available laboratory tests are of no particular use to predict reliably the clinical outcome or to guide in making therapeutic decision. Prospective clinical trials seem necessary to reach such conclusions.     

Gefitinib reverses breast cancer resistance protein-mediated drug resistance

Breast cancer resistance protein (BCRP) is an ATP binding cassette transporter that confers resistance to a series of anticancer agents such as 7-ethyl-10-hydroxycamptothecin (SN-38), topotecan, and mitoxantrone. In this study, we evaluated the possible interaction of gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, with BCRP. BCRP-transduced human epidermoid carcinoma A431 (A431/BCRP) cells acquired cellular resistance to gefitinib, suggesting that BCRP could be one of the determinants of gefitinib sensitivity in a certain sort of cells. Next, the effect of gefitinib on BCRP-mediated drug resistance was examined. Gefitinib reversed SN-38 resistance in BCRP-transduced human myelogenous leukemia K562 (K562/BCRP) or BCRP-transduced murine lymphocytic leukemia P388 (P388/BCRP) cells but not in these parental cells. In addition, gefitinib sensitized human colon cancer HT-29 cells, which endogenously express BCRP, to SN-38. Gefitinib increased intracellular accumulation of topotecan in K562/BCRP cells and suppressed ATP-dependent transport of estrone 3-sulfate, a substrate of BCRP, in membrane vesicles from K562/BCRP cells. These results suggest that gefitinib may overcome BCRP-mediated drug resistance by inhibiting the pump function of BCRP. Furthermore, P388/BCRP-transplanted mice treated with combination of irinotecan and gefitinib survived significantly longer than those treated with irinotecan alone or gefitinib alone. In conclusion, gefitinib is shown to interact with BCRP. BCRP expression in a certain sort of cells is supposed to be one of the determinants of gefitinib sensitivity. Gefitinib inhibits the transporter function of BCRP and reverses BCRP-mediated drug resistance both in vitro and in vivo.     

Gentamicin resistance in Pseudomonas aeruginosa: R-factor-mediated resistance

By disk diffusion antimicrobial susceptibility testing, 11% of 313 consecutive strains of Pseudomonas aeruginosa, examined during July to October 1973, were resistant to gentamicin (minimal inhibitory concentration 12.5 to >100 mug/ml), and a further 31% were moderately resistant (6.25 to 12.5 mug/ml) to gentamicin at the University of Alberta Hospital in Edmonton, Canada. Of 45 gentamicin-resistant strains from that hospital, none possessed R-factors or gentamicin-inactivating enzymes. Eight of 13 strains obtained from three American sources, which contained gentamicin-acetylating (12 strains) or -adenylating (1 strain) activity, conjugally transferred both gentamicin resistance and antibiotic-inactivating activity. P. aeruginosa recipients were much more effective for detection of transferable gentamicin resistance than Escherichia coli recipients, although not all P. aeruginosa were equally as effective as recipients. One strain, POW 151, transferred resistance to both carbenicillin and gentamicin as well as to several other antibiotics. R-factors detected belonged to P-2 and P-3 (Com 6, C) incompatibility groups. Expression of gentamicin resistance due to acetylation of gentamicin was subject to marked phenotypic lag, especially in recipient strain P. aeruginosa 280. This was shown to result in the failure to detect gentamicin resistance transfer if the concentration of gentamicin in selection media was too high (>2.5 mug/ml for strain 280). Some but not all recipients were changed in pyocine type upon acquisition of R-factors.     

Insulin resistance

Insulin resistance is closely associated with fat accumulation in liver. Thus, it has been suggested that insulin resistance is one of the important factor in development of non-alcoholic steatohepatitis(NASH). For example, insulin resistance in adipocyte results in increased lipolysis and delivery of free fatty acids(FFAs) to the liver, which induce fatty liver. If there is insulin resistance in skeletal muscle, hyperinsulinemia and/or hyperglycemia might increase fat accumulation in liver, through, at least in part, increased sterol-regulatory element binding protein-1c(SREBP-1c) activation. However, hepatic insulin resistance might prevent fat accumulation in liver, because insulin strongly induces lipogenesis. Thus, the tissue specific insulin resistance should be considered in the pathogenesis of NASH.     

Aspirin resistance

OBJECTIVE: To review the literature addressing the problem of aspirin resistance in patients with vascular disease. DATA SOURCES: A MEDLINE search (1966-February 2002) was performed. Key search terms included aspirin, resistance, resistant, failure, tolerance, and nonresponder. English-language studies were identified as well as pertinent references from these articles. DATA SYNTHESIS: Aspirin resistance has been reported in patients with cardiovascular, cerebrovascular, and peripheral vascular disease. Because of differences in the definition of resistance, variations in detection methods, and a lack of controlled trials, the true significance of the problem remains unknown. Multiple mechanisms for resistance have been proposed, including increased reactivity to platelet aggregating factors, genetic polymorphism, and alternate pathways for thromboxane synthesis. The studies to date have failed to demonstrate consistent relationships between aspirin's platelet-inhibiting effects, the impact of dosage escalation, and clinical outcomes. CONCLUSIONS: For many patients, aspirin is an effective antithrombotic agent. However, patients taking aspirin may demonstrate highly variable responses to in vitro tests for platelet aggregation and may experience breakthrough thromboembolic events. Although this phenomenon has been termed aspirin resistance, the lack of a uniform definition or agreement on diagnostic criteria precludes definitive recommendations at this time. In addition, strategies are needed to identify patients at risk for aspirin resistance who might benefit from alternative or combined antiplatelet therapy.     

Antibiotic resistance

Resistance to antibiotics is economically and physiologically costly. Control of antibiotic resistance will require aggressive implementation of numerous strategies. Ongoing surveillance is needed to monitor known antibiotic types and to be able to identify the development of other potential types. Early intervention is needed to combat the rising rate of resistance. Persistent use of hygiene measures and controlled use of antibiotics will limit the spread of antibiotic resistance. Health care providers need to monitor adherence to control measures. Hand and environmental control measures remain a critical component of staff education activities. Active management of infections with non-pharmacologic treatments should be promoted. Motivational campaigns will reinforce positive infection control behaviors. Consistent surveillance of antibiotic use will help fulfill the CDC directive to combat antibiotic resistance and keep the population healthy.     

Insulin resistance

There are several mechanisms about high blood pressure induced by insulin resistance in type 2 diabetes. Hyperinsulinemia is rare in Japanese type 2 diabetic patients. Therefore, hyperinsulinemia is not a major cause of high blood pressure in Japanese type 2 diabetic patients. Diabetic nephropathy was associated with high blood pressure. There was a relation between diabetic nephropathy and insulin resistance. Coexistence of essential hypertension with type 2 diabetes. Both essential hypertension and type 2 diabetes were related with insulin resistance. Vascular endothelial dysfunction was associated with insulin resistance. High blood pressure was partially caused by the endothelial dysfunction. The degree of insulin induced vasodilation was reduced in the type 2 diabetic patients with insulin resistance.     

Regulation resistance

Nurses in France are unhappy with their working conditions and have responded with suspicion to a new body set up to regulate them. The Ordre National des Infirmiers has struggled to attract registrants, but there are signs of improvement.     

Insulin resistance

Insulin resistance is one of the most important causes of premature death in developed countries (Turtle 2000). In this article, Alison Jeffery examines the basic pathology of insulin resistance and its effect on metabolic health. The role of the nurse is discussed in relation to prevention, health promotion and drug treatments for the management of this condition.     

Overcoming resistance

Antibodies that prevent HIV from infecting cells are raising hopes of a possible vaccine.     

Antibiotic resistance

Widespread resistance problems exist today in a global sense because of the incorporation of antibiotics with a high resistance potential into animal feeds and because of the uncontrolled use of antibiotics with a high resistance potential in the clinical setting. The only proven method of controlling nonoutbreak resistance problems in hospitals is to limit the hospital formulary to antibiotics with little or no resistance potential. The control of multiresistant organisms in outbreaks occurring in hospitals is best contained using appropriate infection control containment measures. Physicians treating infections in the community, with all other factors being equal, should preferentially select antibiotics with a low resistance potential. The titles and headings of much of the resistance literature are misleading. Articles should not contain fluoroquinolone resistant in the title when ciprofloxacin-resistant organisms are described. Many articles concerning penicillin-resistant pneumococci are entitled fluoroquinolone-resistant S. pneumoniae. These articles describe ciprofloxacin-resistant S. pneumoniae and not resistance to other fluoroquinolones. The same error is perpetuated in describing third-generation cephalosporins and carbapenems. Virtually all of the resistance problems associated with third-generation cephalosporins and carbapenems are due to ceftazidime or imipenem. More precise titling in the literature would remind physicians that antibiotic resistance is related to a specific agent and not class phenomena.     

Antimicrobial resistance

Antimicrobial resistance is not a new concept. For over half a century, health care providers have been faced with this problem. The overuse and misuse of antimicrobial therapy by health care providers has contributed largely to the problem, but several other factors have also been associated with antimicrobial resistance. This article reviews current literature regarding antimicrobial resistance in an effort to educate health care providers to make judicious decisions in the treatment of bacterial infections and stem the rise of antibiotic resistance by carefully scrutinizing prescribing practices. Contributing factors to antimicrobial resistance and recommendations for the control of antimicrobial resistance will be reviewed. Treatment recommendations for common health ailments (i.e., acute otitis media, rhinitis, sinusitis, and pharyngitis) are provided.     

肺炎链球菌大环内酯类耐药表型与相关基因的关系

目的了解肺炎链球菌临床分离株红霉素耐药基因的流行情况和耐药表型的关系。方法对42株肺炎链球菌用E-试验和K-B纸片扩散法检测其对10种抗生素的敏感性;用红霉素和克林霉素双纸片协同试验确定其耐药表型;用PCR扩增这些菌株的耐药基因ermB、mefA和mefE。结果 42株肺炎链球菌中耐药基因ermB总检出率为95.2%(40/42),mefE总检出率为26.1%(11/42),未检出mefA基因。耐药基因组合ermB(+)mefE(-)和ermB(+)mefE(+)占95.2%,两者均呈cMLSB耐药表型。ermB(-)mefE(+)占4.8%(2/42),耐药表型为M型。结论耐药基因ermB导致的cMLSB耐药是大环内酯类耐药的主要原因。大环内酯类抗生素已不是治疗肺炎链球菌的有效药物。