Family Medicine, Department of

Quercetin prevents progression of disease in elastase/LPS-exposed mice by negatively regulating MMP expression

Tue, 28 Sep 2010 00:00:00 GMT

Quercetin prevents progression of disease in elastase/LPS-exposed mice by negatively regulating MMP expression Ganesan, Shyamala; Faris, Andrea N; Comstock, Adam T; Chattoraj, Sangbrita S; Chattoraj, Asamanja; Burgess, John R; Curtis, Jeffrey L; Martinez, Fernando J; Zick, Suzanna; Hershenson, Marc B; Sajjan, Uma S Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, emphysema and irreversible airflow limitation. These changes are thought to be due to oxidative stress and an imbalance of proteases and antiproteases. Quercetin, a plant flavonoid, is a potent antioxidant and anti-inflammatory agent. We hypothesized that quercetin reduces lung inflammation and improves lung function in elastase/lipopolysaccharide (LPS)-exposed mice which show typical features of COPD, including airways inflammation, goblet cell metaplasia, and emphysema. Methods Mice treated with elastase and LPS once a week for 4 weeks were subsequently administered 0.5 mg of quercetin dihydrate or 50% propylene glycol (vehicle) by gavage for 10 days. Lungs were examined for elastance, oxidative stress, inflammation, and matrix metalloproteinase (MMP) activity. Effects of quercetin on MMP transcription and activity were examined in LPS-exposed murine macrophages. Results Quercetin-treated, elastase/LPS-exposed mice showed improved elastic recoil and decreased alveolar chord length compared to vehicle-treated controls. Quercetin-treated mice showed decreased levels of thiobarbituric acid reactive substances, a measure of lipid peroxidation caused by oxidative stress. Quercetin also reduced lung inflammation, goblet cell metaplasia, and mRNA expression of pro-inflammatory cytokines and muc5AC. Quercetin treatment decreased the expression and activity of MMP9 and MMP12 in vivo and in vitro, while increasing expression of the histone deacetylase Sirt-1 and suppressing MMP promoter H4 acetylation. Finally, co-treatment with the Sirt-1 inhibitor sirtinol blocked the effects of quercetin on the lung phenotype. Conclusions Quercetin prevents progression of emphysema in elastase/LPS-treated mice by reducing oxidative stress, lung inflammation and expression of MMP9 and MMP12.

Bacterial Pneumonias during an Influenza Pandemic: How Will We Allocate Antibiotics?

Tue, 01 Sep 2009 00:00:00 GMT

Bacterial Pneumonias during an Influenza Pandemic: How Will We Allocate Antibiotics? Cinti, Sandro K.; Barnosky, Andrew R.; Gay, Steven E.; Goold, Susan Dorr; Lozon, Marie M.; Kim, Kristin; Rodgers, Phillip E.; Baum, Nancy M.; Cadwallender, Bruce A.; Collins, Curtis D.; Wright, Carrie M.; Winfield, Robert A. We are currently in the midst of the 2009 H1N1 pandemic, and a second wave of flu in the fall and winter could lead to more hospitalizations for pneumonia. Recent pathologic and historic data from the 1918 influenza pandemic confirms that many, if not most, of the deaths in that pandemic were a result of secondary bacterial pneumonias. This means that a second wave of 2009 H1N1 pandemic influenza could result in a widespread shortage of antibiotics, making these medications a scarce resource. Recently, our University of Michigan Health System (UMHS) Scarce Resource Allocation Committee (SRAC) added antibiotics to a list of resources (including ventilators, antivirals, vaccines) that might become scarce during an influenza pandemic. In this article, we summarize the data on bacterial pneumonias during the 1918 influenza pandemic, discuss the possible impact of a pandemic on the University of Michigan Health System, and summarize our committee's guiding principles for allocating antibiotics during a pandemic.

Delphi-Derived Development of a Common Core for Measuring Complementary and Alternative Medicine Prevalence

Fri, 01 May 2009 00:00:00 GMT

Delphi-Derived Development of a Common Core for Measuring Complementary and Alternative Medicine Prevalence Lachance, Laurie L.; Hawthorne, Victor; Brien, Sarah; Hyland, Michael E.; Lewith, George T.; Verhoef, Marja J.; Warber, Sara; Zick, Suzanna Abstract Assessing complementary and alternative medicine (CAM) use remains difficult due to many problems, not the least of which is defining therapies and modalities that should be considered as CAM. Members of the International Society for Complementary Medicine Research (ISCMR) participated in a Delphi process to identify a core listing of common CAM therapies presently in use in Western countries. Lists of practitioner-based and self-administered CAM were constructed based on previous population-based surveys and ranked by ISCMR researchers by perceived level of importance. A total of 64 (49%) ISCMR members responded to the first round of the Delphi process, and 39 of these (61%) responded during the second round. There was agreement across all geographic regions (United States, United Kingdom, Canada, and Western Europe) for the inclusion of herbal medicine, acupuncture, homeopathy, Traditional Chinese Medicine (TCM), chiropractic, naturopathy, osteopathy, Ayurvedic medicine, and massage therapy in the core practitioner-based CAM list, and for homeopathy products, herbal supplements, TCM products, naturopathic products, and nutritional products in the self-administered list. This Delphi process, along with the existing literature, has demonstrated that (1) separate lists are required to measure practitioner-based and self-administered CAM; (2) timeframes should include both ever use and recent use; (3) researchers should measure and report prevalence estimates for each individual therapy so that direct comparisons can be made across studies, time, and populations; (4) the list of CAM therapies should include a core list and additionally those therapies appropriate to the geographic region, population, and the specific research questions addressed, and (5) intended populations and samples studied should be defined by the researcher so that the generalizability of findings can be assessed. Ultimately, it is important to find out what CAM modality people are using and if they are being helped by these interventions.

Psychosocial Factors in Risk of Cervical Intraepithelial Lesions

Wed, 01 Apr 2009 00:00:00 GMT

Psychosocial Factors in Risk of Cervical Intraepithelial Lesions Wilkerson, Jennifer E.; Bailey, Joanne M.; Bieniasz, Mary E.; Murray, Sandra I.; Ruffin, Mack T. Abstract Background: This study examines the relationship among psychosocial factors, behavioral risks for abnormal cervical cytology, and abnormal cervical cytology. Methods: A self-administered questionnaire was used to measure perceived stress, discrimination, lifetime stressful events, optimism, social support, and psychological state. Women with normal Pap smears attending a primary care clinic and women attending a colposcopy clinic because of an abnormal Pap smear were eligible. The scores between the two groups were compared. Results: A total of 265 women participated in the study. There were no significant relationships between psychosocial factors and cervical cytology status. In a regression model, age (B=0.057, p=0.001) was predictive of having abnormal cervical cytology. Smoking was correlated with an increased family Apgar score (p=0.021), Perceived Stress Scale (PSS) score (p=0.049), and Revised Life Stressor Checklist score (p<0.001). A higher mean number of lifetime male partners was related to increased family Apgar score (p=0.012), Revised Life Stressor Checklist score (p<0.001), and major event discrimination (p<0.001). Earlier age at coitarche was associated with increased family Apgar score (p<0.001). Conclusions: These results do not support that psychosocial factors play a role in the risk of developing abnormal cervical cytology. Behavioral risks for developing abnormal cervical cytology are associated with life stressors, family function, and perceived discrimination.