trans-Activation and repression properties of the novel nonsteroid glucocorticoid receptor ligand 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(1-methylcyclohexen-3-y1)-1H-[1]benzopyrano[3,4-f]quinoline (A276575) and its four stereoisomers

Glucocorticoids are potent anti-inflammatory and immunosuppressant agents. However, they also produce serious side effects that limit their usage. It has been proposed that anti-inflammatory properties of glucocorticoids are caused mostly by repression of activator protein 1- and nuclear factor kappabeta-stimulated synthesis of inflammatory mediators, whereas most of their adverse effects are associated with trans-activation of genes involved with metabolic processes. Our laboratories have sought to discover novel glucocorticoid receptor (GR) ligands that have high repression but low trans-activation activities. We describe here cellular properties of 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(1-methylcyclohexen-3-y1)-1H-[1]benzopyrano[3,4-f]quinoline (A276575) and its four enantiomers. Similar to dexamethasone, A276575 exhibited high affinity for GR and potently repressed interleukin (IL) 1beta-stimulated IL-6 production in human skin fibroblasts, prostaglandin (PG) E(2) production in A549 human lung epithelial cells, and concanavalin A-induced monocyte proliferation. In contrast to dexamethasone, A276575 caused smaller induction of aromatase activity in human skin fibroblasts and antagonized dexamethasone-induced activation of an mouse mammary tumor virus-glucocorticoid-response element (GRE) reporter gene construct. Among the four enantiomers of A276575, the two (-)-enantiomers showed 10- to 30-fold higher affinities for GR than their respective (+)-enantiomers. Both (-)-Syn and (-)-Anti enantiomers of A276575 were potent inhibitors of IL-1beta-stimulated PGE2 production in A549 lung epithelial cells; unexpectedly, however, only the (-)-Anti enantiomer inhibited regulated on T-cell activation, normal T-cell expressed and secreted (RANTES) production in A549 cells. In summary, A276575 is a novel, nonsteroidal GR ligand that possesses high repression activities against inflammatory mediator production but has lower GRE trans-activation activities than traditional steroids. Differential repression of RANTES and PGE2 production in a cell by the two (-)-enantiomers of A276575 illustrates the complexity of repression by GR.     

Credentialing the public health workforce: an idea whose time has come.

The importance of a well-prepared public health workforce is widely recognized and appreciated. Strategies for enhancing workforce capacity and competency have been discussed by agencies, associations, committees, and expert panels since the landmark 1988 Institute of Medicine report. The need to foster the development of incentives for lifelong learning and career growth is of current interest to national public health associations and federal agencies. The fact that the public health workforce is not a single profession, but rather a fabric of many professions dedicated to a common endeavor, creates challenges to any singular approach. This article explores the relationships among competency, certification, and accreditation and summarizes the expert panel dialogue on workforce development incentives, specifically regarding certification and credentialing. The authors challenge public health leaders to become actively involved in framing the issues so the best possible strategies can be developed.     

Safety and efficacy of two dose formulations of alicaforsen enema compared with mesalazine enema for treatment of mild to moderate left-sided ulcerative colitis: a randomized, double-blind, active-controlled trial

BACKGROUND: Alicaforsen is an antisense oligonucleotide inhibitor of intercellular adhesion molecule 1 protein expression with activity in subjects with ulcerative colitis and pouchitis. AIM: To compare the effects of alicaforsen enema to standard of care mesalazine (mesalamine) enema in subjects with mild to moderate active left-sided ulcerative colitis. METHOD: A randomized, double-blind, active-controlled multicentre clinical trial. Subjects received a nightly enema of 120 mg alicaforsen (n=55), 240 mg alicaforsen (n=50), or 4 g mesalazine (n=54) for 6 weeks, followed by a 24-week monitoring period. The primary end point was Disease Activity Index at week 6. Clinical improvement, remission and relapse were secondary end points. RESULTS: No significant difference was observed between treatment arms in the primary end point. However, the median duration of response to alicaforsen enema treatment was two- to threefold longer (128 and 146 days) in comparison with mesalazine (54 days). Complete mucosal healing occurred in 24% of the 240 mg alicaforsen group, when compared with 17% in the mesalazine. CONCLUSIONS: Alicaforsen enema demonstrated an acute response and safety profile similar to mesalazine enema, but was differentiated by a more durable response. The extended length of remission suggests that alicaforsen enema treatment may have a disease modifying effect.     

长鞭红景天化学成分的研究

长鞭红景天化学成分的研究彭江南，葛永潮，李晓晖（军事医学科学院放射医学研究所，北京１００８５０）红景天是滋补强壮药物，目前正引起人们极大的兴趣，现已有一些产品上市。我们曾对数种红景天的化学成分进行过研究［１～４］。长鞭红景天（Ｒｈｏｄｉｏｌａｆａｓｔ...     

Amplifying diffusion of health information in low-literate populations through adult education health literacy classes

Over the next decade, as literacy rates are predicted to decline, the health care sector faces increasing challenges to effective communication with low-literate groups. Considering the rising costs of health care and the forthcoming changes in the American health care system, it is imperative to find nontraditional avenues through which to impart health knowledge and functional skills. This article draws on classroom observations and qualitative interviews with 21 students and 3 teachers in an adult education health literacy class to explore the efficacy of using adult education courses to teach functional health literacy skills to low-literate populations. Data were analyzed using a combination of thematic and content analyses. Results describe the motivation of students to share information within the classroom and with friends and family outside the classroom. This article also provides several recommendations to help ensure accuracy of diffused information both within and outside of the classroom. Ultimately, this study suggests that the adult education system is in a prime position to impart functional health literacy skills to low-literate populations in the classroom. Significantly, this study demonstrates that adult education students themselves may be a powerful vehicle for health communication beyond the walls of the classroom.     

Building capacity for success: the Tobacco Technical Assistance Consortium

The Master Settlement Agreement with the tobacco industry has infused resources into tobacco control and prevention, which has helped fund tobacco control programs at the national, state, and local levels. Many tobacco control programs face challenges in areas such as strategic planning, fiscal operations, advocacy, and personnel management. To provide technical assistance to these programs, the Robert Wood Johnson Foundation, the American Legacy Foundation, and the American Cancer Society combined resources to fund the Tobacco Technical Assistance Consortium (TTAC). TTAG, housed at the Rollins School of Public Health at Emory University, provides support for tobacco control programs and matches requests for technical assistance with consultants who have the appropriate expertise. TTAC is a valuable addition to tobacco control and prevention resources and is a viable component within a school of public health.     

29例筛窦癌的放射治疗

筛窦癌发病率低,就诊时病期晚,５年无瘤生存率为３０％～５０％。由于解剖部位的限制以及局部浸润,放射和手术均有一定难度。作者回顾性分析皇家Ｍａｒｇｒｅｔ医院１９７６～１９９４年收治的２９例浸润性筛窦癌根治性放射治疗的疗效和影响预后因素。男性２４例,女性４例,中位年龄６２岁,中位随访时间４年。常有鼻出血、鼻塞、疼痛及视力改变等。起病到确诊的平均时间为９个月。２７例吸烟,１０例从事伐木或镍的开采与提炼。　　治疗前均经临床及影像学检查。仅３例局限于筛窦,余侵犯鼻腔、蝶窦、眼眶、上颌窦、额窦及脑内等。Ｔ１…     

Lymphomatous superficial lymph nodes: US detection

Superficial adenopathy is the most frequent clinical manifestation of lymphoma, both at initial workup and later when disease recurs. Data obtained by means of physical examination and ultrasonography (US) of the cervicosupraclavicular, axillary, and inguinal regions were compared for 120 patients, 60 at the time of initial staging and 60 during follow-up for a previously treated lymphoma. Twenty-nine in the second group had recurrent disease, as confirmed with histologic examination. For all 120 patients, US revealed clinically impalpable lesions in an average of 10.8% of cases for the cervicosupraclavicular region, 17.9% for the axillary region, and 4.1% for the inguinal region. Eight of the 29 relapses were not detected at physical examination, and three were demonstrated solely with US. These findings emphasize the value of US exploration of the superficial node-bearing regions in patients with lymphoma, during both initial staging and follow-up.