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Piscataway, NJ, United States

Subramaniam P.,Rutgers University | Lee K.-B.,Rutgers University | Garfunkel E.,Rutgers University | Mainelis G.,Rutgers University | And 8 more authors.
PLoS ONE | Year: 2014

Acting as fuel combustion catalysts to increase fuel economy, cerium dioxide (ceria, CeO2) nanoparticles have been used in Europe as diesel fuel additives (Envirox™). We attempted to examine the effects of particles emitted from a diesel engine burning either diesel (diesel exhaust particles, DEP) or diesel doped with various concentrations of CeO2 (DEP-Env) on innate immune responses in THP-1 and primary human peripheral blood mononuclear cells (PBMC). Batches of DEP and DEP-Env were obtained on three separate occasions using identical collection and extraction protocols with the aim of determining the reproducibility of particles generated at different times. However, we observed significant differences in size and surface charge (zeta potential) of the DEP and DEP-Env across the three batches. We also observed that exposure of THP-1 cells and PBMC to identical concentrations of DEP and DEP-Env from the three batches resulted in statistically significant differences in bioreactivity as determined by IL-1β, TNF-α, IL-6, IFN-γ, and IL-12p40 mRNA (by qRT-PCR) and protein expression (by ELISPOT assays). Importantly, bioreactivity was noted in very tight ranges of DEP size (60 to 120 nm) and zeta potential (-37 to -41 mV). Thus, these physical properties of DEP and DEP-Env were found to be the primary determinants of the bioreactivity measured in this study. Our findings also point to the potential risk of over- or under- estimation of expected bioreactivity effects (and by inference of public health risks) from bulk DEP use without taking into account potential batch-to-batch variations in physical (and possibly chemical) properties. © 2014 Sarkar et al.

Dheda K.,UCT | Dheda K.,University of Cape Town | Dheda K.,University College London | Schwander S.K.,Center for Global Public Health | And 3 more authors.
Respirology | Year: 2010

Tuberculosis (TB) is an international public health priority and kills almost two million people annually. TB is out of control in Africa due to increasing poverty and HIV coinfection, and drug-resistant TB threatens to destabilize TB control efforts in several regions of the world. Existing diagnostic tools and therapeutic interventions for TB are suboptimal. Thus, new vaccines, immunotherapeutic interventions and diagnostic tools are urgently required to facilitate TB control efforts. An improved understanding of the immunopathogenesis of TB can facilitate the identification of correlates of immune protection, the design of effective vaccines, the rational selection of immunotherapeutic agents, the evaluation of new drug candidates, and drive the development of new immunodiagnostic tools. Here we review the immunology of TB with a focus on aspects that are clinically and therapeutically relevant. An immunologically orientated approach to tackling TB can only succeed with concurrent efforts to alleviate poverty and reduce the global burden of HIV. © 2010 Asian Pacific Society of Respirology.

Nakamura T.,The New School | Schwander S.,The New School | Schwander S.,Center for Global Public Health | Donnelly R.,The New School | And 9 more authors.
Clinical and Vaccine Immunology | Year: 2013

A major hypothesis regarding the cause of chronic fatigue syndrome (CFS) is immune dysregulation, thought to be reflected in upregulated proinflammatory cytokines leading to the symptoms that are characteristic of this illness. Because the symptoms worsen with physical exertion or sleep loss, we hypothesized that we could use these stressors to magnify the underlying potential pathogenic abnormalities in the cytokine systems of people with CFS. We conducted repeat blood sampling for cytokine levels from healthy subjects and CFS patients during both postexercise and total sleep deprivation nights and assayed for protein levels in the blood samples, mRNA activity in peripheral blood lymphocytes (PBLs), and function in resting and stimulated PBLs. We found that these environmental manipulations did not produce clinically significant upregulation of proinflammatory cytokines. These data do not support an important role of immune dysregulation in the genesis of stress-induced worsening of CFS. Copyright © 2013, American Society for Microbiology. All Rights Reserved.

Schwander S.,The New School | Schwander S.,Center for Global Public Health | Dheda K.,University of Cape Town | Dheda K.,University College London
American Journal of Respiratory and Critical Care Medicine | Year: 2011

The study of human pulmonary immunity against Mycobacterium tuberculosis (M.tb) provides a unique window into the biological interactions between the human host and M.tb within the bronchoalveolar microenvironment, the site of natural infection. Studies of bronchoalveolar cells (BACs) and lung tissue evaluate innate, adaptive, and regulatory immune mechanisms that collectively contribute to immunological protection or its failure. In aerogenically M.tb-exposed healthy persons lung immune responses reflect early host pathogen interactions that may contribute to sterilization, the development of latent M.tb infection, or progression to active disease. Studies in these persons may allow the identification of biomarkers of protective immunity before the initiation of inflammatory and disease-associated immunopathological changes. In healthy close contacts of patients with tuberculosis (TB) and during active pulmonary TB, immune responses are compartmentalized to the lungs and characterized by an exuberant helper T-cell type 1 response, which as suggested by recent evidence is counteracted by local suppressive immune mechanisms. Here we discuss how exploring human lung immunity may provide insights into disease progression and mechanisms of failure of immunological protection at the site of the initial host-pathogen interaction. These findings may also aid in the identification of new biomarkers of protective immunity that are urgently needed for the development of new and the improvement of current TB vaccines, adjuvant immunotherapies, and diagnostic technologies. To facilitate further work in this area, methodological and procedural approaches for bronchoalveolar lavage studies and their limitations are also discussed.

Emmanuel F.,University of Manitoba | Salim M.,National Institute of Health | Akhtar N.,National Institute of Health | Arshad S.,Center for Global Public Health | Reza T.E.,National Institute of Health
Sexually Transmitted Infections | Year: 2013

Objectives In an effort to fully analyse and understand the HIV situation and its epidemiology in Pakistan, a bilateral collaboration between the National AIDS Control Program and the Canadian International Development Agency resulted in the establishment of an effective second-generation surveillance (SGS) system for HIV/AIDS between 2004 and 2012 in accordance with the published guidelines. This paper presents findings from the 4th round of SGS. Methods A mapping exercise was initially conducted for size estimations of the key vulnerable populations: people who inject drugs (PWIDs), male sex workers (MSWs), hijra sex workers (HSWs), and female sex workers (FSWs), followed by an Integrated Behavioral and Biological Surveillance in 20 selected cities across Pakistan. Results The estimated sizes of the four key populations mapped in the 20 cities were 89 178 FSWs, 46 351 PWIDs, 23 317 HSWs and 19 119 MSWs. The HIV sero-prevalence among PWIDs was the highest among all key populations surveyed at 37.8% (CI 37.3 to 38.3) nationally, followed by a prevalence of 7.2% (CI 6.8 to 7.5) among HSWs, 3.1% (CI 2.8 to 3.4) among MSWs and 0.8% (CI 0.4 to 1.0) for FSWs. Various key risk behaviours, that is, sharing of syringes by PWIDs and inconsistent use of condoms by sex workers, were documented. Conclusions Pakistan's HIV epidemic that once was characterised primarily by transmission among PWIDs is now increasingly characterised by significant sexual transmission, and all types of sex workers (male, hijra and female) exhibit epidemiological proportions of infection. There is a need to develop concrete strategic plans for each vulnerable subpopulation, initially focusing prevention resources on those with a higher risk or vulnerability.

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