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Therapeutic Promise (therapeutic + promise)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Obesity-related cardiovascular disease: implications of obstructive sleep apnea

DIABETES OBESITY & METABOLISM, Issue 3 2006
R. Wolk
Obesity and obstructive sleep apnea (OSA) often coexist. OSA has been linked to cardiovascular disease. Thus, OSA may contribute to the cardiovascular consequences of obesity. In this review, we explore clinical and pathophysiological interactions between obesity, cardiovascular disease and OSA. We discuss the mechanisms whereby OSA may contribute to hypertension, atherosclerosis, insulin resistance and atrial fibrillation associated with obesity, and emphasize the potential implications for understanding why only a subgroup of obese patients develop cardiovascular disease. Identification of the OSA-dependent and OSA-independent pathways in the cardiovascular pathophysiology of obesity may hold clinical and therapeutic promise. [source]

TREM-1 promotes survival during septic shock in mice

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2007
Sébastien Gibot Dr.
Abstract Triggering receptor expressed on myeloid (TREM)-1 is integral to the inflammatory response occurring during septic shock, although its precise function has yet to be determined. Here we show that in vivo silencing of TREM-1 using siRNA duplexes in a fecal peritonitis mouse model resulted in a blunted inflammatory response and increased mortality. This was associated with impaired bacterial clearance related to marked inhibition of the neutrophil oxidative burst. By contrast, TREM-1 -silenced mice were highly resistant to a lethal endotoxin challenge, while partial silencing of TREM-1 in the bacterial peritonitis model produced a significant survival benefit. These data highlight the crucial role of the TREM-1 pathway in mounting an adequate inflammatory and cytotoxic response to polymicrobial sepsis, and both the therapeutic promise and potential risks of its modulation. [source]

Upregulation of K2P5.1 potassium channels in multiple sclerosis

ANNALS OF NEUROLOGY, Issue 1 2010
Stefan Bittner BSc
Objective Activation of T cells critically depends on potassium channels. We here characterize the impact of K2P5.1 (KCNK5; TASK2), a member of the 2-pore domain family of potassium channels, on T-cell function and demonstrate its putative relevance in a T-cell,mediated autoimmune disorder, multiple sclerosis (MS). Methods Expression of K2P5.1 was investigated on RNA and protein level in different immune cells and in MS patients' biospecimens (peripheral blood mononuclear cells, cerebrospinal fluid cells, brain tissue specimen). Functional consequences of K2P5.1 expression were analyzed using pharmacological modulation, small interfering RNA (siRNA), overexpression, electrophysiological recordings, and computer modeling. Results Human T cells constitutively express K2P5.1. After T-cell activation, a significant and time-dependent upregulation of K2P5.1 channel expression was observed. Pharmacological blockade of K2P5.1 or knockdown with siRNA resulted in reduced T-cell functions, whereas overexpression of K2P5.1 had the opposite effect. Electrophysiological recordings of T cells clearly dissected K2P5.1-mediated effects from other potassium channels. The pathophysiological relevance of these findings was demonstrated by a significant K2P5.1 upregulation in CD4+ and CD8+ T cells in relapsing/remitting MS (RRMS) patients during acute relapses as well as higher levels on CD8+ T cells of clinically isolated syndrome, RRMS, and secondary progressive multiple sclerosis patients during clinically stable disease. T cells in the cerebrospinal fluid from MS patients exhibit significantly elevated K2P5.1 levels. Furthermore, K2P5.1-positive T cells can be found in inflammatory lesions in MS tissue specimens. Interpretation Selective targeting of K2P5.1 may hold therapeutic promise for MS and putatively other T-cell,mediated disorders. ANN NEUROL 2010;68:58,69 [source]

Inhibitory oligodeoxynucleotides , therapeutic promise for systemic autoimmune diseases?

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2005
P. Lenert
Summary Recent studies have shed new light on a possible link between the innate activation of plasmocytoid dendritic cells and marginal zone B cells and the pathogenesis of systemic lupus erythematosus. Animal studies have identified that this response requires the Toll-like receptor 9 (TLR9). Engagement of the TLR9 by various ligands, including non-canonical CpG-motifs, can cause or aggravate pathogenic autoantibody production and cytokine secretion in lupus. Attempts to neutralize this activity either by blocking the acidification of the endosomal compartment with chloroquine and related compounds, or by preventing the interaction between the CpG-DNA sequences and TLR9 using inhibitory oligonucleotides could be a promising therapeutic option for lupus. [source]