Diminished lipoxin biosynthesis in severe asthma.

Rationale And Objectives: Severe asthma is characterized by increased airway inflammation that persists despite therapy with corticosteroids. It is not, however, merely an exaggeration of the eosinophilic inflammation that characterizes mild to moderate asthma; rather, severe asthma presents unique features. Although arachidonic acid metabolism is well appreciated to regulate airway inflammation and reactivity, alterations in the biosynthetic capacity for both pro- and antiinflammatory eicosanoids in severe asthma have not been determined.

Cyclooxygenase 2 plays a pivotal role in the resolution of acute lung injury.

Acute lung injury (ALI) is a severe illness with excess mortality and no specific therapy. In its early exudative phase, neutrophil activation and accumulation in the lung lead to hypoxemia, widespread tissue damage, and respiratory failure. In clinical trials, inhibition of proinflammatory mediators has not proven effective.

An initiative in mentoring to promote residents' and faculty members' careers.

Internal medicine trainees and faculty recognize the value of effective mentoring to help meet the personal and professional needs of residents. However, the paradigm of the mentor-trainee relationship is seriously threatened by increased clinical, research, and administrative demands on both faculty and housestaff. Moreover, the current criteria for promotion in most teaching hospitals emphasize scholarship, rather than citizenship, so activities such as mentoring devolve to a lower priority.

A molecular defect in intracellular lipid signaling in human neutrophils in localized aggressive periodontal tissue damage.

Host defense mechanisms are impaired in patients with congenital neutrophil (polymorphonuclear neutrophils (PMN)) defects. Impaired PMN chemotaxis is observed in localized aggressive periodontitis (LAP), a familial disorder characterized by destruction of the supporting structures of dentition. In the present studies, we sought evidence for molecular events underlying this aberrant human PMN phenotype.

Exploring new approaches to the treatment of asthma: potential roles for lipoxins and aspirin-triggered lipid mediators.

The prevalence of asthma continues to increase and its optimal treatment remains a challenge. During asthma, leukotrienes and prostaglandins are generated in human airways, leading to bronchoconstriction and airway inflammation. Several pharmaceutical agents are currently available to inhibit the formation or action of these lipid mediators, but asthmatic individuals have heterogeneous and often incomplete therapeutic responses.

Lipoxins and aspirin-triggered lipoxins in airway responses.

Here, we have demonstrated potent inhibition of allergen-mediated pulmonary inflammation and airway hyper-responsiveness by a novel dual-pronged action of LX's. Moreover, these results indicate that LX's play pivotal and previously unappreciated roles in regulating allergy and pulmonary inflammation.

Cyclooxygenase-2-deficient mice are resistant to endotoxin-induced inflammation and death.

Sepsis is a systemic inflammatory response to a blood-borne infection that is associated with an extremely high rate of morbidity and mortality. The present study investigates the role of cyclooxygenase (COX)-2 in host responses to bacterial endotoxemia. After administration of Escherichia coli lipopolysaccharide, 50% of wild-type mice die within 96 h.

Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A(4).

The prevalence of asthma continues to increase and its optimal treatment remains a challenge. Here, we investigated the actions of lipoxin A(4) (LXA(4)) and its leukocyte receptor in pulmonary inflammation using a murine model of asthma. Allergen challenge initiated airway biosynthesis of LXA(4) and increased expression of its receptor.