Pioglitazone is as effective as dexamethasone in a cockroach allergen-induced murine model of asthma

<p>Abstract</p> <p>Background</p> <p>While glucocorticoids are currently the most effective therapy for asthma, associated side effects limit enthusiasm for their use. Peroxisome proliferator-activated receptor-γ (PPAR-γ) activators include the synthetic thiazolidinediones (TZDs) which exhibit anti-inflammatory effects that suggest usefulness in diseases such as asthma. How the ability of TZDs to modulate the asthmatic response compares to that of glucocorticoids remains unclear, however, because these two nuclear receptor agonists have never been studied concurrently. Additionally, effects of PPAR-γ agonists have never been examined in a model involving an allergen commonly associated with human asthma.</p> <p>Methods</p> <p>We compared the effectiveness of the PPAR-γ agonist pioglitazone (PIO) to the established effectiveness of a glucocorticoid receptor agonist, dexamethasone (DEX), in a murine model of asthma induced by cockroach allergen (CRA). After sensitization to CRA and airway localization by intranasal instillation of the allergen, Balb/c mice were challenged twice at 48-h intervals with intratracheal CRA. Either PIO (25 mg/kg/d), DEX (1 mg/kg/d), or vehicle was administered throughout the period of airway CRA exposure.</p> <p>Results</p> <p>PIO and DEX demonstrated similar abilities to reduce airway hyperresponsiveness, pulmonary recruitment of inflammatory cells, serum IgE, and lung levels of IL-4, IL-5, TNF-α, TGF-β, RANTES, eotaxin, MIP3-α, Gob-5, and Muc5-ac. Likewise, intratracheal administration of an adenovirus containing a constitutively active PPAR-γ expression construct blocked CRA induction of Gob-5 and Muc5-ac.</p> <p>Conclusion</p> <p>Given the potent effectiveness shown by PIO, we conclude that PPAR-γ agonists deserve investigation as potential therapies for human asthma.</p

The peroxisome: still a mysterious organelle

More than half a century of research on peroxisomes has revealed unique features of this ubiquitous subcellular organelle, which have often been in disagreement with existing dogmas in cell biology. About 50 peroxisomal enzymes have so far been identified, which contribute to several crucial metabolic processes such as β-oxidation of fatty acids, biosynthesis of ether phospholipids and metabolism of reactive oxygen species, and render peroxisomes indispensable for human health and development. It became obvious that peroxisomes are highly dynamic organelles that rapidly assemble, multiply and degrade in response to metabolic needs. However, many aspects of peroxisome biology are still mysterious. This review addresses recent exciting discoveries on the biogenesis, formation and degradation of peroxisomes, on peroxisomal dynamics and division, as well as on the interaction and cross talk of peroxisomes with other subcellular compartments. Furthermore, recent advances on the role of peroxisomes in medicine and in the identification of novel peroxisomal proteins are discussed

Nancy Cunard's English journey

This essay analyses Nancy Cunard's contribution to the struggle for racial justice in England and her work with the black communities in Liverpool and London (whose histories and experiences differ radically from their counterparts in the United States) in the 1940s. It chronicles for the first time her campaign to safeguard the African collections in the Liverpool Museum and her specific contribution to the archive of black British history. This includes not only the monumental the Negro Anthology (1934) but also the tract, The White Man's Duty (1943) arguing for an end to British imperialism and for race relations legislation. Cunard is situated within a history of the Communist left in Britain and the United States. Her insistence on the primacy of race differentiates her from other white left activists in her day for whom issues of gender and race were or secondary importance compared to those of class (Cunard, 1944). Using unpublished archive material from the Harry Ransom Center in Austin, Texas I show that Cunard's work constitutes one segment in the rich and varied mosaic of black cultural activity in the 1930s and 1940s and discuss how Cunard knew and worked alongside some of the key figures in the black British politics of her day including Una Marson, Learie Constantine, John Carter, Harold Moody, Rudolph Dunbar and Paul Robeson. A prolific writer, publisher and political activist, Cunard presented a white readership with documentation which prompted them to question their own prejudice and rendered problematic the imaging of black people as fixed embodiments of a Eurocentric sense of reality. Cunard's work in the 1930s and 1940s predates the sailing of the Empire Windrush and the accelerated immigration to Britain from the Commonwealth after the Nationality Act of 1948. It adds to our knowledge of earlier black history, narratives, settlements, and anti-racist struggles

Innovative traffic control technology and practice in Europe.

Federal Highway Administration, Office of International Programs, Washington, D.C.Mode of access: Internet.Author corporate affiliation: American Trade Initiatives, Alexandria, Va.Subject code: CICSubject code: EMSubject code: FGFSubject code: HBSubject code: HBECSubject code: HBEESubject code: IEBSubject code: KNSubject code: FSSubject code: PMMOSubject code: WOHSubject code: WW*I

SGLT2 Mediates Glucose Reabsorption in the Early Proximal Tubule

Mutations in the gene encoding for the Na+-glucose co-transporter SGLT2 (SLC5A2) associate with familial renal glucosuria, but the role of SGLT2 in the kidney is incompletely understood. Here, we determined the localization of SGLT2 in the mouse kidney and generated and characterized SGLT2-deficient mice. In wild-type (WT) mice, immunohistochemistry localized SGLT2 to the brush border membrane of the early proximal tubule. Sglt2−/− mice had glucosuria, polyuria, and increased food and fluid intake without differences in plasma glucose concentrations, GFR, or urinary excretion of other proximal tubular substrates (including amino acids) compared with WT mice. SGLT2 deficiency did not associate with volume depletion, suggested by similar body weight, BP, and hematocrit; however, plasma renin concentrations were modestly higher and plasma aldosterone levels were lower in Sglt2−/− mice. Whole-kidney clearance studies showed that fractional glucose reabsorption was significantly lower in Sglt2−/− mice compared with WT mice and varied in Sglt2−/− mice between 10 and 60%, inversely with the amount of filtered glucose. Free-flow micropuncture revealed that for early proximal collections, 78 ± 6% of the filtered glucose was reabsorbed in WT mice compared with no reabsorption in Sglt2−/− mice. For late proximal collections, fractional glucose reabsorption was 93 ± 1% in WT and 21 ± 6% in Sglt2−/− mice, respectively. These results demonstrate that SGLT2 mediates glucose reabsorption in the early proximal tubule and most of the glucose reabsorption by the kidney, overall. This mouse model mimics and explains the glucosuric phenotype of individuals carrying SLC5A2 mutations