IntroductionSustained neutrophilic infiltration is known to contribute to organ damage, such as acute lung injury (ALI). CXC chemokine receptor 2 (CXCR2) is the major receptor regulating inflammatory neutrophil recruitment in acute and chronic inflamed tissues. The purpose of this study was to investigate the functional relevance of the CXCR2 inhibitor SB225002 in LPS-induced acute lung injury.Material and methodsMale C57BL/6 mice were randomly divided into the following four experimental groups (n = 10 per group): untreated group (control group, Ctr); LPS-treated ALI group (LPS group, LPS); LPS + PBS-treated group (LPS + PBS); and SB225002-treated ALI group (LPS + SB225002). Twenty-four hours after treatment, the blood, bronchoalveolar lavage fluid (BALF), and lung tissue were collected and wet/dry ratio, protein concentration, myeloperoxidase (MPO) activity, neutrophil infiltration, and inflammatory cytokine secretion in lung tissue were measured. The pathologic changes in the lungs were examined using optical microscopy. Survival rates were recorded at 120 h in all four groups, in other experiments.ResultsHistology findings revealed that the SB225002-treated group had significantly milder lung injury compared to the LPS-induced ALI and the PBS-treated control groups. Treatment with SB225002 significantly attenuated LPS-induced lung injury and suppressed the inflammatory responses in damaged lung tissue. Compared to the PBS-treated control group, treatment with SB225002 dramatically decreased the lung wet/dry ratio, protein concentration, and infiltration of neutrophils in lung tissue. Therefore, SB225002 treatment appeared to inhibit the production of inflammatory cytokines and increase survival time compared to the PBS-treated control group.ConclusionsTogether, these data demonstrated that inhibition of CXCR2 signaling by SB225002 could ameliorate LPS-induced acute lung injury, by reducing neutrophil recruitment and vascular permeability. SB225002 may be further developed as a potential novel treatment for LPS-induced ALI.

Background Data that incorporate the full complexity of healthy beverage intake and voiding frequency do not exist; therefore, clinicians reviewing bladder habits or voiding diaries for continence care must rely on expert opinion recommendations. Objective To use data-driven cluster analyses to reduce complex voiding diary variables into discrete patterns or data cluster profiles, descriptively name the clusters, and perform validity testing. Method Participants were 352 community women who filled out a 3-day voiding diary. Six variables (void frequency during daytime hours, void frequency during nighttime hours, modal output, total output, total intake, and body mass index) were entered into cluster analyses. The clusters were analyzed for differences by continence status, age, race (Black women, n = 196 White women, n = 156), and for those who were incontinent, by leakage episode severity. Results Three clusters emerged, labeled descriptively as Conventional, Benchmark, and Superplus. The Conventional cluster (68% of the sample) demonstrated mean daily intake of 45 ±13 ounces; mean daily output of 37 ± 15 ounces, mean daily voids 5 ± 2 times, mean modal daytime output 10±0.5 ounces, and mean nighttime voids 1±1 times. The Superplus cluster (7% of the sample) showed double or triple these values across the 5 variables, and the Benchmark cluster (25%) showed values consistent with current popular recommendations on intake and output (e.g., meeting or exceeding the 8 × 8 fluid intake rule of thumb). The clusters differed significantly (p < .05) by age, race, amount of irritating beverages consumed, and incontinence status. Discussion Identification of three discrete clusters provides for a potential parsimonious but data-driven means of classifying individuals for additional epidemiological or clinical study. The clinical utility rests with potential for intervening to move an individual from a high risk to low risk cluster with regards to incontinence.

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