Publications

Osteopenia and periarticular bony erosion are consequences of chronic inflammatory autoimmune disease due to an imbalance of osteoclast activity relative to new bone formation. Osteoclasts, which are specialized as the only bone resorbing cell type, are differentiated from hematopoietic myeloid precursor cells. Inflammatory signals mediated by multiple types of immune cells and cytokines have significant influence over osteoclast differentiation and function through direct effects on osteoclast precursors and indirect effects via osteoblasts and other cells in the bony microenvironment including synovial cells, stromal cells, osteocytes and chondrocytes. Recent studies have demonstrated that osteoclasts themselves express a number of immune receptors and are regulated similarly to macrophages and dendritic cells, closely related cells in the innate immune system. Though we are only beginning to understand the roles of innate immune receptors in osteoclasts, some of these receptors have been shown to be critical regulators of differentiation and function of osteoclasts. Osteoclasts likely function as the innate immune cells of the bone, thus are highly regulated to appropriately respond to stress and inflammatory changes in their microenvironment.

Asthma is a common but complex respiratory disease caused by the interaction of genetic and environmental factors. Significant racial and ethnic disparities in prevalence, mortality and drug response have been described. These disparities may be explained by racial and ethnic-specific variation in genetic, environmental, social and psychological risk factors. In addition, race, ethnicity and social class are important proxies for unmeasured factors that influence health outcomes. Herein, we review salient differences in the etiologies of asthma by race, ethnicity and social class, and argue for their continued use as variables in asthma research.

PURPOSE

The purpose of this study was to identify relationships between medical, functional, economic, oral health, social, religious, and psychological factors and under-eating in homebound older adults. The focus of the study was on identifying potentially modifiable factors amenable to social and behavioral interventions.

DESIGN AND METHODS

A total of 230 homebound older adults who were currently receiving home health services participated in interviews in their homes using a questionnaire to assess eating behaviors and factors that could possibly affect those eating behaviors. Interviewers measured height and weight, and participants completed three 24-hr dietary recalls.

RESULTS

The mean age of participants was 79.1 years. The sample comprised 78% women and 38% African Americans. We found that 70% of participants were under-eating, defined as not consuming enough calories to maintain their current body weight. Participants who were at higher risk of under-eating included men, those receiving either infrequent care or very frequent care by a caregiver, those who had been hospitalized prior to receipt of home health services, and those with a higher body mass index.

IMPLICATIONS

Findings from the study have implications for both practice and policy. Experts must develop evidence-based interventions targeted at under-eating in this particularly vulnerable and growing population of homebound older adults. This study provides an initial foundation for the development of targeted evidence-based behavioral nutritional interventions that are noninvasive and cost effective.

Deletion of integrin alphav beta6 has been associated with significant protection in experiments where lung injury was induced by bleomycin, lipophilic polysaccharides, and high tidal volume ventilation. This has led to the suggestion that antibody blockade of this integrin is a novel therapy for acute lung injury. We questioned whether beta6 gene deletion would also protect against Pseudomonas aeruginosa-induced acute lung injury. Wild-type and littermate beta6-null mice, as well as recombinant soluble TGF-beta receptor type II-Fc (rsTGF-betaRII-Fc) and anti-alphav beta6 treated wild-type mice, were instilled with live P. aeruginosa. Four or 8 h after bacterial instillation, the mice were euthanized, and either bronchoalveolar lavage fluid or lung homogenates were obtained. Deletion of the beta6 gene resulted in an overall increase in inflammatory cells in the lungs. Bacterial numbers from the lung homogenates of infected beta6-null mice were significantly decreased compared to the numbers in the wild-type mice (1.6 x 10(6) CFU versus 4.2 x 10(6) CFU [P < 0.01]). There were no significant differences in P. aeruginosa-mediated increases in lung endothelial permeability between wild-type and beta6-null mice. Similarly, pretreatment with the alphav beta6 antibody or with rsTGF-betaRII-Fc did not significantly affect the P. aeruginosa-induced lung injury or rate of survival compared to pretreatment with control immunoglobulin G. We conclude that deletion or inhibition of the integrin alphav beta6 did not protect animals from P. aeruginosa-induced lung injury. However, these therapies also did not increase the lung injury, suggesting that host defense was not compromised by this promising new therapy.

BACKGROUND

HIV infection is associated with an increased risk of coronary artery disease, but the contribution of inflammation versus antiretroviral drugs is not well understood. Fibrinogen is an inflammatory factor associated with atherosclerosis.

METHODS

A total of 1131 HIV-infected patients and 281 controls [from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based study of cardiovascular risk assessment] in the Study of Fat Redistribution and Metabolic Change in HIV infection (FRAM) had plasma fibrinogen levels measured. Multivariable linear regression identified factors associated with fibrinogen.

RESULTS

HIV-infected patients had higher levels of fibrinogen compared with controls (males: 25 mg/dl higher, P = 0.006; females: 21 mg/dl higher, P = 0.39). Among HIV-infected persons, median levels of fibrinogen were 11% higher in patients currently using any protease inhibitor (PI) compared with those not using a PI (P < 0.0001). The strongest univariate associations were with the individual PIs, ritonavir and indinavir. Patients taking indinavir boosted with ritonavir had median fibrinogen levels 8% higher than those on indinavir alone (P = 0.049). Lower levels of fibrinogen were seen in those HIV-infected patients currently using any nonnucleoside reverse transcriptase inhibitor (NNRTI) compared to those not using an NNRTI (nevirapine -14.4%, P < 0.0001; efavirenz -7%, P = 0.0002). The associations of ritonavir, indinavir, efavirenz and nevirapine with fibrinogen levels persisted after multivariable analysis and were independent of other antiretroviral use.

CONCLUSION

Protease inhibitor use is associated with elevated fibrinogen levels which may contribute to increased risk of atherosclerosis in HIV-infected patients. Conversely, NNRTI use is associated with lower fibrinogen levels which may decrease risk of atherosclerosis.