Abstract: One-third of humans carry Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB) where microbe/host immune response interactions result in persistence or active TB. However, immune mediators associated with human TB remain poorly defined. Through a series of comparative studies of lung immune response of TB cases at the time of diagnosis and patients with other infectious lung diseases and volunteers, we found that TB cases expressed significantly higher levels of mediators that counteract Th1-type and innate immunity critical for containment of M. tuberculosis. Despite the concomitant heightened levels of Th1-type mediators, they are likely rendered ineffectual by high levels of intracellular (e.g., SOCS) and extracellular (e.g., IL-10) immune suppressors. These modulators are a direct response to M. tuberculosis as many suppressive factors declined to the levels of controls by 30 days of anti-TB treatment while most Th1-type and innate immune mediators rose above the pre-treatment levels. Parallel laboratory studies and monitored lung alveolar macrophage effector, nitric oxide synthase-2 (being shown critical for killing M. tuberculosis), support that M. tuberculosis actively promotes down-modulatory mediators to counteract Th1-type/innate immunity as an immunopathological strategy. Our studies highlight the potential application of immune mediators as surrogate markers for TB diagnosis or treatment response. ... Read more

Abstract: A lot has been learned since the 2001 mail anthrax attack. Authors analyzed the readiness of science and US government agencies in handling future bioterror attacks and proposed measures that would drastically improve the response efficiency and reduce the damage. ... Read more

“Between 500 and 1,000 microbial species colonize the mammalian colon to a density of approximately 10¹² bacteria per gram of content, comprising in total 100 times more cells than those that make up the host itself,” said Drs. Lanning and Knight in an article published in this issue of the journal. Given the immensity of the bacteria living inside our bodies, it is almost a miracle that they do not cause more trouble than they occasionally do (e.g., diarrhea, enterocolitis, imbalance of intestinal flora, etc.).

On the contrary, the commensal bacterial flora in the gut performs important, unconventional tasks ... Read more

Abstract: Gastric cancer may not affect a lot of people in North America and Europe, but it is one of the top killer cancers in Asia. A persistent infection with the bacterium Helicobacter pylori in the stomach contributes greatly to the occurrence of gastric cancer in Asia. It turns out that Asian bacterial strains are more potent in transforming normal cells to cancerous ones than "Western" or African strains. ... Read more

Introduction

The natural product pool, which includes many glycosylated secondary metabolites, is the source of over half of the world’s drug leads. For example, the antibiotics vancomycin and erythromycin, the antitumor compounds bleomycin and doxorubicin, and the antifungal agents amphotericin and nystatin all contain essential sugar attachments. Carbohydrate groups of natural product-based drugs have long been known to generally influence pharmacokinetic properties and there is an increasing recognition that these carbohydrate appendages also play a key role in drug-target interactions. These findings suggest that the alteration of glycosylation patterns on secondary metabolites is a potential strategy for the generation of novel ... Read more

One of the major therapeutic challenges that face modern clinicians is the development of bacterial resistance to antibiotics. Currently, antibiotic resistance is a major problem in the treatment of staphylococcal, enterococcal, pneumocystis, helicobacter, and mycobacterial infections, to name a few. While there are several different mechanisms by which this occurs, the common pathway in the development of bacterial resistance has been the widespread use of broad-spectrum antibiotics as single agents.

In the work summarized here, we devised a novel antibiotic, which could be used to overcome bacterial resistance to standard antibiotics. The concept is based on two principles. 1) Use of ... Read more

Other Names: telithromycin.

Maker: Aventis Pharmaceuticals Inc.

Disease Treated: KETEK is an antibiotic for treating respiratory infections such as acute bacterial exacerbation of bronchitis (AECB), acute bacterial sinusitis (AS) and community-acquired pneumonia (CAP), caused by susceptible strains of bacteria (e.g., Streptococcus pneumoniae).

Approval Status: Approved by the U.S. FDA on April 1, 2004 as an antibacterial agent to treat specific respiratory infections caused by susceptible bacterial infections.

Chemical/Biological Nature: KETEK’s active ingredient is an 812.03-dalton, semisynthetic antibacterial agent of the ketolide class known as telithromycin, with an empirical formula of C_⁴³H_⁶⁵N_⁵O_¹⁰. In its native form it ... Read more

Problems associated with conventional cancer therapy are numerous, but two stand out: lack of specificity and the inability to totally eradicate all cancerous cells. The former leads to severe, sometimes intolerable, adverse effects, whereas the latter contributes to the dismal prognosis for a variety of cancer types.

Effective cancer therapy should consist of components targeting both normoxic and hypoxic tumor tissues.

The progression of solid tumors requires a sufficient blood supply to deliver both nutrients and oxygen. However, the growth rate of malignant tumors often outpaces angiogenesis. In addition, the tumor vasculature is often poorly organized and leaky in nature. Consequently, the ... Read more