Role of kinin B2 receptor signaling in the recruitment of circulating progenitor cells with neovascularization potential.

Reduced migratory function of circulating angiogenic progenitor cells (CPCs) has been associated with impaired neovascularization in patients with cardiovascular disease (CVD). Previous findings underline the role of the kallikrein-kinin system in angiogenesis. We now demonstrate the involvement of the kinin B2 receptor (B(2)R) in the recruitment of CPCs to sites of ischemia and in their proangiogenic action.

Caspase inhibitor zVAD.fmk reduces infarct size after myocardial ischaemia and reperfusion in rats but not in mice.

Objective: Apoptosis of cardiomyocytes has been suggested to contribute to outcome following myocardial ischaemia and reperfusion (MI/R). Caspase inhibitors were developed as potential therapeutics for MI/R. However, various reports using the broad-spectrum caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.

Toll-like receptors in endocrine disease and diabetes.

The body's ability to keep a steady homeostatic state is crucial to health and life. This involves providing an adequate response to a variety of challenges both physical and mental, such as microbial invasion and emotional distress. Interplay between the neuroendocrine and immune systems is essential in either case.

Lipoteichoic acid induces delayed myocardial protection in isolated rat hearts: a comparison with endotoxin.

Objective: Preconditioning with bacterial wall fragments lipopolysaccharide (LPS) or lipoteichoic acid (LTA) reduce myocardial infarct size after ischaemia and reperfusion (I/R) in rats. Preconditioning with LTA reduces neutrophil accumulation during reperfusion and thereby ameliorates one of myocardial reperfusion injury's most important mechanisms. In this study, we use an ex vivo model of regional myocardial I/R to investigate LTA versus LPS induced preconditioning in a system devoid of leukocytes.

Rosiglitazone is cardioprotective in a murine model of myocardial I/R.

The peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a regulator of anti-inflammatory genes. One of its agonists, rosiglitazone-widely used in the treatment of type 2 diabetes mellitus-has recently been reported to increase the risk for myocardial infarction. In contrast, various studies provide evidence for a rosiglitazone-induced cardioprotection in different models of acute myocardial I/R.

Biglycan is required for adaptive remodeling after myocardial infarction.

Background: After myocardial infarction (MI), extensive remodeling of extracellular matrix contributes to scar formation and preservation of hemodynamic function. On the other hand, adverse and excessive extracellular matrix remodeling leads to fibrosis and impaired function. The present study investigates the role of the small leucine-rich proteoglycan biglycan during cardiac extracellular matrix remodeling and cardiac hemodynamics after MI.

Effect of aprotinin on renal dysfunction in patients undergoing on-pump and off-pump cardiac surgery: a retrospective observational study.

Background: Aprotinin is used during cardiac surgery for its blood-saving effects. However, reports suggest a possible association between use of this drug and increased renal dysfunction and mortality. We investigated the effect of aprotinin on renal dysfunction in cardiac surgery, considering the cofactors on-pump versus off-pump surgery and co-medication with angiotensin-converting enzyme (ACE) inhibitors.

IFN-alpha skews monocytes into CD56+-expressing dendritic cells with potent functional activities in vitro and in vivo.

The antitumor effect of IFN-alpha is mediated by the activation of CTLs, NK cells, and the generation of highly potent Ag-presenting dendritic cells (IFN-DCs). In this study, we show that IFN-DCs generated in vitro from monocytes express CD56 on their surface, a marker which has been thought to be specific for NK cells. FACS analyses of CD56(+) and CD56(-) IFN-DCs showed a nearly identical pattern for most of the classical DC markers.

Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility: role of toll-like receptor 9.

Aims: Myocardial function is severely compromised during sepsis. Several underlying mechanisms have been proposed. The innate immune system, i.

Inflammatory response and cardioprotection during open-heart surgery: the importance of anaesthetics.

Open-heart surgery triggers an inflammatory response that is largely the result of surgical trauma, cardiopulmonary bypass, and organ reperfusion injury (e.g. heart).

CpG oligonucleotide activates Toll-like receptor 9 and causes lung inflammation in vivo.

Background: Bacterial DNA containing motifs of unmethylated CpG dinucleotides (CpG-ODN) initiate an innate immune response mediated by the pattern recognition receptor Toll-like receptor 9 (TLR9). This leads in particular to the expression of proinflammatory mediators such as tumor necrosis factor (TNF-alpha) and interleukin-1beta (IL-1beta). TLR9 is expressed in human and murine pulmonary tissue and induction of proinflammatory mediators has been linked to the development of acute lung injury.

Inducible nitric oxide synthase and heme oxygenase-1 in the lung during lipopolysaccharide tolerance and cross tolerance.

Objective: Pretreatment with low-dose lipopolysaccharide protects cells/organs against a subsequent lethal Gram-negative (lipopolysaccharide tolerance) or Gram-positive (cross tolerance) stimulus. We determined whether this occurs in the rat lung. The involvement of inducible nitric oxide synthase and heme oxygenase-1 was evaluated.

Heat shock inhibits lipopolysaccharide-induced tissue factor activity in human whole blood.

Background: During gram-negative sepsis, lipopolysaccharide (LPS) induces tissue factor expression on monocytes. The resulting disseminated intravascular coagulation leads to tissue ischemia and worsens the prognosis of septic patients. There are indications, that fever reduces the mortality of sepsis, the effect on tissue factor activity on monocytes is unknown.

Carcinogenic hypergastrinemia: signet-ring cell carcinoma in a patient with multiple endocrine neoplasia type 1 with Zollinger-Ellison's syndrome.

Context: Gastric neuroendocrine tumors are rare neoplasms that originate from gastric enterochromaffin-like (ECL) cells in the oxyntic mucosa. Gastrin and its derivates have been reported to regulate epithelial cell proliferation, migration, and differentiation. Mutations in the epithelial cadherin (E-cadherin) gene have been shown to be associated with the occurrence of diffuse gastric carcinomas in affected families.

Pam3CSK4 and LTA-TLRs ligands associated with microdomains induce IL8 production in human adrenocortical cancer cells.

Bacterially derived ligands, Pam3CSK4 and LPS, can directly impact adrenal glands steroidogenesis through microdomain-related TLR1/2 and 4, respectively, and indirectly via immune cell-derived cytokines. The bilateral immunoadrenal relationship plays an important role in the proper functioning of both systems. CXC chemokine-dependent immune cell infiltration into adrenocortical carcinomas (ACC), which correlates with poor prognosis, is a common phenomenon.

The fibrin-derived peptide Bbeta15-42 is cardioprotective in a pig model of myocardial ischemia-reperfusion injury.

Objective: The fibrin-derived peptide Bbeta15-42 has been shown to reduce infarct size in rodent models of ischemia-reperfusion injury. To increase its potential for translation into the clinic, we studied the effects of Bbeta15-42 in pigs, whose coronary anatomy is similar to that of humans. In addition, we evaluated the pharmacokinetics and safety of Bbeta15-42 in several species, including humans.

Clinical chemistry reference database for Wistar rats and C57/BL6 mice.

Clinical chemistry data are decisive for evaluating altered organ function or damage in experimental animals. Few publications provide reliable clinical chemistry reference intervals, and analytical methods are often not described. Here, we investigated common clinical chemistry values in adult male and female Wistar rats and C57/BL6 mice (n=30/group).

The effects of the fibrin-derived peptide Bbeta(15-42) in acute and chronic rodent models of myocardial ischemia-reperfusion.

Many compounds have been shown to prevent reperfusion injury in various animal models, although to date, translation into clinic has revealed several obstacles. Therefore, the National Heart, Lung, and Blood Institute convened a working group to discuss reasons for such failure. As a result, the concept of adequately powered, blinded, randomized studies for preclinical development of a compound has been urged.

Toll-like receptor 9 expression in murine and human adrenal glands and possible implications during inflammation.

Context: Sepsis is a leading cause of death in the Western world and can be associated with failure of the hypothalamic-pituitary-adrenal axis. A coordinated response of the adrenal and immune system is of vital importance for survival during sepsis. Within the immune response, Toll-like receptors (TLRs) play a crucial role by recognizing pathogen-associated molecules such as bacterial DNA.

[New reflections on inflammation and coagulation].

Inflammation is the host's defense mechanism to infection or injury, including surgical procedures. In the clinical setting non-infectious inflammation, activation of the coagulation cascade and deterioration of endothelial function play an important role in cardiology (e.g.

Nitric oxide and pro-inflammatory cytokines correlate with pain intensity in chronic pain patients.

Objective: Inflammatory cytokines as well as nitric oxide (NO) play a key role in the pathogenesis of persistent and exaggerated pain states. To document this, we investigated whether a range of cytokines and NO were detectable in the plasma of chronic pain patients and whether cytokine and NO levels correlated with pain severity.

Methods: Plasma samples of 94 chronic pain patients and 6 healthy volunteers were obtained.

The role of toll-like receptors in the immune-adrenal crosstalk.

Sepsis and septic shock remain major health concerns worldwide, and rapid activation of adrenal steroid release is a key event in the organism's first line of defense during this form of severe illness. Toll-like receptors (TLRs) are critical in the early immune response upon bacterial infection, and recent data from our lab demonstrate a novel link between the innate immune system and the adrenal stress response mediated by TLRs. Glucocorticoids and TLRs regulate each other in a bidirectional way.