新的TB用藥概念，可殺latent TB，讓TB的protein沒法degredattion!!

非常了不起
大部份抗生素都是趁細菌在replication的時候下手殺菌
但對TB這種難得分裂的細菌就無法下手
所以才要高劑量長時間的給予，讓病人受苦
但冬眠的細菌仍要大便
把大便筒塞住他就完了
所以這個藥如果ok
可以大幅度縮短TB療程




New Approach to Treating Tuberculosis

Targeting nonreplicative bacteria might avert long courses of therapy for TB patients.

In contrast to most bacterial pathogens, Mycobacterium tuberculosis is a slow-growing organism with a propensity for latency, which means that patients with this infection require treatment with multiple drugs for many months. To remain healthy, every cell, including single-cell organisms, requires proper levels of each protein that it produces. This fact means that a balance must exist between synthesis and degradation of proteins. Many antibacterials target synthesis of bacterial proteins, but none inhibit degradation of proteins. Unlike other bacteria, mycobacteria have proteasomes — a key site of protein degradation — and might be susceptible to inhibitory agents.

A multi-institutional team has identified a class of compounds that inhibit proteasomes in M. tuberculosis without inhibiting proteasomes in human cells. The team reports that two compounds, GL5 and HT1171, rapidly, powerfully, and permanently inhibit mycobacterial proteasomes and kill mycobacteria that are in a latent nonreplicating state. At concentrations necessary to kill bacteria, the compounds demonstrated no toxicity to animal (eukaryotic) cells.

Comment: Antibacterials that target synthesis of M. tuberculosis proteins have been only moderately successful for treating infection. The long multidrug courses of therapy that are required to treat tuberculosis often lead to patient nonadherence and to development of drug-resistant organisms. This new approach to targeting degradation of M. tuberculosis proteins appears — at this very early stage — to be both a potent and nontoxic approach to treating one of the world's great killers. As such, this development is very exciting.

— Anthony L. Komaroff, MD

Published in Journal Watch General Medicine October 13, 2009
Citation(s):

Lin G et al. Inhibitors selective for mycobacterial versus human proteasomes. Nature 2009 Oct 1; 461:621. (http://dx.doi.org/10.1038/nature08357)

* Medline abstract (Free)


https://docs.google.com/fileview?id=0B278nGJMQBk7M2UzNjgxZWEtMmU3ZS00MTAxLTljYzAtNjMwMDQzNjRlMjZh&hl=zh_TW

http://docs.google.com/present/edit?id=0AW78nGJMQBk7ZGc1d3FjYmpfMjMwaGdkNHJmZG4&hl=zh_TW

留言

張貼留言

這個網誌中的熱門文章

即便是用IGRA, 有時也要等大於三個月才能決定TB contact

圖片
接觸TB後，TST大抵上2-12週轉陽，IGRA大抵上6-10週，但IGRA可以長到3個月以上 TB Tests Can Have a Lengthy Window Period Two studies suggest that interferon- release assay conversion sometimes occurs more than 3 months after exposure to active tuberculosis. Increasingly, interferon- release assays (IGRAs) are being used for diagnosing latent tuberculosis (TB). Although the tuberculin skin test (TST) traditionally used for this purpose converts to positive within 2 to 12 weeks after an individual is exposed to someone with active TB, the interval for IGRA conversion has remained unclear. Current guidelines recommend repeating an initially negative IGRA after 6 to 10 weeks, but this recommendation is not based on controlled studies. Two recent investigations address this issue. Anibarro and colleagues conducted a longitudinal prospective analysis among contacts of TB patients in Spain. The 152 contacts received a TST and an IGRA at first visit; for individuals with negative or conflicting results, t
閱讀完整內容

白宮為了掌控醫療費用，傾向大型醫療，個體戶勢必受挫

所以一旦政府介入，中外醫療提供者都傾向大型化…… independent practice -> dreaming 診所評鑑??應該擋住! http://www.medscape.com/viewarticle/727420 Physicians Say White House Should Not Write Off Small Practices August 24, 2010 — In a newly published article, the White House is advising physicians to accept a life in Big Medicine — as a hospital employee or member of a large group practice — in the wake of healthcare reform. Some leaders of organized medicine, however, are objecting to the government message. "We're not ready to write off the small practices," J. Fred Ralston Jr, MD, president of the American College of Physicians, told Medscape Medical News. "We think there needs to be more than one delivery model." "America is not a one-size-fits-all country," added M. Todd Williamson, MD, a neurologist from Lawrenceville, Georgia, and spokesperson for a coalition of medical societies opposed to the new healthcare reform law, now called the Affordable Care Act. Dr. Ralston and Dr.
閱讀完整內容

老美接受LTBI treatment的人，不到一半完治，和duration成正比

This study shows that although acceptance of LTBI treatment is relatively high (83%), the proportion completing is low (47%). When the product of these two proportions is calculated, we see that completion was achieved by only 39% of persons who were offered LTBI treatment. The major risk factor for noncompletion was being prescribed the 9-month INH regimen. As shown in Figure 1, when the proportions completing the three most commonly prescribed regimens are compared, it can be seen that there is an inverse relationship between length of the regimen prescribed and the proportion completing treatment. The increased completion that we observed with the 4-month rifampin regimen is consistent with previous reports.[18–20] It is of interest to note that if completion of the 9-month regimen were defined as completion of at least 6 months of INH, the noncompletion rate of the 9-month regimen, 42.9%, would have been almost identical to that of the 6-month regimen, 44.8%. Thus, prescribing the
閱讀完整內容