Soluble triggering receptor expressed on myeloid cell-1 is increased in patients with ventilator-associated pneumonia: a preliminary report.

Rationale: The diagnosis of ventilator-associated pneumonia (VAP) can be difficult. Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) has been reported to be elevated in BAL fluid from patients with VAP.

Objectives: To evaluate the utility of sTREM-1 in the diagnosis of VAP in BAL fluid and the fluid collected in the expiratory trap from the ventilator, the exhaled ventilator condensate (EVC).

Doxycycline decreases monocyte chemoattractant protein-1 in human lung epithelial cells.

Certain antibiotics possess anti-inflammatory properties and could potentially be used to treat inflammatory lung diseases associated with an influx of monocytes such as panbronchiolitis, asthma, cystic fibrosis, and bronchitis. Doxycycline is reported to possess anti-inflammatory effects. Monocyte chemoattractant protein-1 (MCP-1) is a major inflammatory cytokine and a powerful chemoattractant for monocytes.

Doxycycline modulates nitric oxide production in murine lung epithelial cells.

Many effective therapeutic agents exhibit effects that are different from their intended primary mode of action. Antibiotics such as doxycycline and erythromycin A are no exception. They also display anti-inflammatory activity.

Heat decreases formoterol delivery.

Study Objectives: Based on anecdotal reports of formoterol aggregating in mailboxes in the summer in Arizona, we examined the effect of heat on formoterol as well as on drug delivery.

Design: Formoterol capsules in original blister packaging were heated to 40 to 70 degrees C (104 to 158 degrees F) for 3 h and at 70 degrees C (158 degrees F) for 15 to 180 min. Capsules were removed from packaging, and a vacuum setup was used to dispense the formoterol into a filter using the device provided by the manufacturer.

Serine protease inhibitors modulate smoke-induced chemokine release from human lung fibroblasts.

Smoking is associated with lung inflammation and a protease-antiprotease imbalance. We previously reported that cigarette smoke extract (CSE) stimulates human lung fibroblasts to release chemotactic cytokines. We hypothesized that serine protease inhibitors might modulate lung fibroblast release of chemotactic cytokines in response to CSE.

Serine protease inhibitors modulate chemotactic cytokine production by human lung fibroblasts in vitro.

Chemotactic chemokines can be released from lung fibroblasts in response to interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. An imbalance between proteases and antiproteases has been observed at inflammatory sites, and, therefore, protease inhibitors might modulate fibroblast release of chemotactic cytokines. To test this hypothesis, serine protease inhibitors (FK-706, alpha(1)-antitrypsin, or N(alpha)-p-tosyl-L-lysine chloromethyl ketone) were evaluated for their capacity to attenuate the release of neutrophil chemotactic activity (NCA) or monocyte chemotactic activity (MCA) from human fetal lung fibroblasts (HFL-1).

Cigarette smoke decreases inducible nitric oxide synthase in lung epithelial cells.

Cigarette smoking has been associated with decreased exhaled nitric oxide (NO). To investigate the mechanism of this decrease, the effects of a cigarette smoke extract were evaluated a murine lung epithelial cell line (LA-4), a human lung epithelial cell line (A549), and primary cultures of human lung epithelial cells induced to produce NO by cytokines. NO production was evaluated by measuring nitrite, a stable end product of NO, in cell culture supernatant fluids.

Peroxynitrite enhances interleukin-10 reduction in the release of neutrophil chemotactic activity.

Peroxynitrite, formed by nitric oxide and superoxide, has been shown to nitrate and reduce the function of proinflammatory proteins such as interleukin (IL)-8, monocyte chemoattractant protein-1, and eotaxin, but in contrast, to enhance the function of the anti-inflammatory cytokine IL-10 in reducing IL-1 release from blood monocytes. However, the effect of nitrated IL-10 on release of proinflammatory cytokines from lung epithelial cells is unknown. We hypothesized that peroxynitrite would enhance the capacity of human IL-10 to reduce inflammatory mediators released by epithelial cells.

Molecular characterization and analysis of the biosynthetic gene cluster for the azoxy antibiotic valanimycin.

Streptomyces viridifaciens MG456-hF10 produces the antibiotic valanimycin, a naturally occurring azoxy compound. Valanimycin is known to be derived from valine and serine with the intermediacy of isobutylamine and isobutylhydroxylamine, but little is known about the stages in the pathway leading to the formation of the azoxy group. In previous studies, a cosmid containing S.