The concept of in vivo airway tissue engineering.

We investigated whether decellularized pig tracheas could regenerate in vivo, without being recellularized before transplantation, using the own body as bioreactor. Decellularized pig tracheal scaffolds were intraoperative conditioned with mononuclear cells and growth and differentiation factors. During the postoperative period, the in situ regeneration was boosted by administering bioactive molecules to promote peripheral mobilization and differentiation of stem/progenitor cells and ultimately the regenerative process.

FOSL2 promotes leptin gene expression in human and mouse adipocytes.

The adipocyte-derived hormone leptin is a critical regulator of many physiological functions, ranging from satiety to immunity. Surprisingly, very little is known about the transcriptional pathways that regulate adipocyte-specific expression of leptin. Here, we report studies in which we pursued a strategy integrating BAC transgenic reporter mice, reporter assays, and chromatin state mapping to locate an adipocyte-specific cis-element upstream of the leptin (LEP) gene in human fat cells.

Asymmetric dimethylarginine may mediate increased heat pain threshold in experimental chronic kidney disease.

Background: Thermal sensitivity in uraemia is decreased. Non-selective synthetic nitric oxide synthase (NOS) inhibitors significantly attenuate thermal hyperalgesia in preclinical models. The aim of our study was to evaluate the effect of experimental uraemia, which is associated with an increase of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA), on thermal sensitivity in rats.

Distinct effects of NPY13-36, a specific NPY Y2 agonist, in a model of rodent endotoxemia on leukocyte subsets and cytokine levels.

Even now, sepsis remains a major problem in modern clinical medicine, leading to systemic inflammatory response including altered leukocyte subset distribution and increased cytokine release. As immune cells are known to express NPY receptors, we investigated the effects of a specific NPY Y(2) receptor agonist (NPY(13-36)) and/or the corresponding Y(2) receptor antagonist BIIE0246 treatment on blood (by FACS analyses) and tissue (by immunohistochemistry) leukocyte subsets as well as on levels of IL-4, IL-6, IL-10, TNF-α, INF-γ (by Cytometric Bead Array) in healthy and acutely endotoxemic rats. Results show a significant decrease in blood monocytes after LPS challenge in endotoxemic control animals (by 93%), in endotoxemic NPY(13-36) treated animals (by 83%) and in endotoxemic BIIE0246 treated animals (by 88%) as compared to the corresponding healthy controls.

In vitro evidence of involvement of the epithelial y+ transporter in β-defensin production on the ocular surface.

To analyse the hypothesis as to whether there is a functional relationship between human cationic amino acid transporters (hCATs, y(+) transporter, the main transporter of L-arginine and L-lysine) and human β-defensin (important components of immune function) production on the ocular surface, arginase and nitrate monoxide synthase (NOS), enzymes that compete for L-arginine, were inhibited by norNOHA (N(omega)-hydroxy-nor-L-arginine) and/or L-NAME (NG-nitro-L-arginine methyl ester) in cultured human corneal epithelial cells. In addition, the transport activity of hCAT proteins was inhibited or activated through α-tocopherol or PMA (phorbol myristate acetate), respectively. Concentrations of the human inducible β-defensins (hBD) 2 and 3 were determined by ELISA experiments.

Human obesity reduces the number of hepatic leptin receptor (ob-R) expressing NK cells.

Objective: In the industrialized world, obesity is an increasing socioeconomic health problem. Obese subjects have a higher risk of developing several types of cancer. NK cells are an integral component of the innate immune system, able to destruct tumor cells.

Short-term and long-term leptin exposure differentially affect human natural killer cell immune functions.

Epidemiological studies have indicated that obesity is associated with a higher risk for certain cancers caused by elevated levels of adipocyte-derived hormones. Leptin, one such hormone produced by adipocytes, is a major regulator of metabolism and has also been shown to modulate immunity. However, its role in regulating human natural killer (NK) cell functions is largely unknown.

A mutation in Myo15 leads to Usher-like symptoms in LEW/Ztm-ci2 rats.

The LEW/Ztm-ci2 rat is an animal model for syndromal deafness that arose from a spontaneous mutation. Homozygous animals show locomotor abnormalities like lateralized circling behavior. Additionally, an impaired vision can be observed in some animals through behavioral studies.

Diet-induced obesity, exogenous leptin-, and MADB106 tumor cell challenge affect tissue leukocyte distribution and serum levels of cytokines in F344 rats.

The adipocyte-derived catabolic protein leptin alters cell-mediated immunity and cytokine crosstalk. This may provide new insights into the altered immune response, seen in obese individuals. Therefore, we determined the tissue distribution of immune cells in diet-induced obese (dio) and normal weight F344 rats challenged with MADB106 tumor cells or leptin.

Dipeptidyl peptidase IV (DPP4)-deficiency attenuates diet-induced obesity in rats: possible implications for the hypothalamic neuropeptidergic system.

The underlying mechanisms controlling food intake and satiety are thoroughly controlled, but seem to be insufficient under conditions of almost unlimited food supply. Hence, overweight and obesity are serious problems especially in industrialized countries. To assess the possible influence of CD26, exerting a dipeptidyl peptidase activity (DPP4) cleaving several energy homeostasis-relevant peptides, we investigated wild type and DPP4-deficient dark agouti rats in a model of diet-induced obesity and found a reduced weight gain in DPP4-deficient rats.

Obesity and the associated mediators leptin, estrogen and IGF-I enhance the cell proliferation and early tumorigenesis of breast cancer cells.

Breast cancer continues to be a major cause of cancer deaths in women. Estrogen, which is also produced by the adipose tissue, is held responsible for the elevated risk of breast cancer in obese women. However, the adipose tissue secrets hormones and adipokines such as leptin and IGF-I and these substances could also contribute to an increased breast cancer risk for obese women.

Altered phenotype of NK cells from obese rats can be normalized by transfer into lean animals.

In diet-induced obese rats, leptin-mediated natural killer (NK) cell activation has been demonstrated to be impaired by abrogated intracellular JAK2-STAT3 signaling. The contribution of the obese microenvironment to this NK cell dysfunction and its reversibility remains elusive. In this study, the functions of NK cells from diet-induced obese rats after adoptive transfer into lean littermates were investigated using in vivo and in vitro approaches.

Phenotyping of congenic dipeptidyl peptidase 4 (DP4) deficient Dark Agouti (DA) rats suggests involvement of DP4 in neuro-, endocrine, and immune functions.

Background: Treatment of diabetes type 2 using chronic pharmacological inhibition of dipeptidyl peptidase 4 (DP4) still requires an in-depth analysis of models for chronic DP4 deficiency, because adverse reactions induced by some DP4 inhibitors have been described.

Methods: In the present study, a novel congenic rat model of DP4 deficiency on a "DP4-high" DA rat genetic background was generated (DA.F344-Dpp4(m)/ SvH rats) and comprehensively phenotyped.

Obesity and NK cells affect the expression of the long form of the leptin receptor Ob-Rb in liver of F344 rats.

In obesity, the regulatory effects of leptin, a primarily adipocyte-derived hormone, are severely disturbed affecting the control of energy homeostasis and immune functions. In addition, recent studies indicate that specific immune cells can affect glucose and lipid metabolism of liver. However, the contribution of body weight and immune cells, such as Natural Killer (NK) cells, to the regulation of the leptin-receptor expression remains elusive.

Peripheral but not central leptin treatment increases numbers of circulating NK cells, granulocytes and specific monocyte subpopulations in non-endotoxaemic lean and obese LEW-rats.

Leptin, a hormone mainly generated by adipocytes, acts centrally in the hypothalamus to regulate body weight and energy expenditure. However, there is strong evidence that leptin is also involved in cell-mediated immunity and cytokine crosstalk. In the present study the effects of diet-induced obesity and central and peripheral leptin treatment on leukocyte subsets and cytokine production was investigated.

Resistance of Janus kinase-2 dependent leptin signaling in natural killer (NK) cells: a novel mechanism of NK cell dysfunction in diet-induced obesity.

Leptin acts not only as an anorexigenic hormone but also regulates cell-mediated immunity via leptin receptors (Ob-R) expressed on T and B lymphocytes. However, the impact of leptin on natural killer (NK) cells is currently elusive. We evaluated leptin effects on NK cells in relation to the body weight in rats using in vivo and in vitro approaches.

Obesity influences the food consumption and cytokine pattern in ghrelin-treated endotoxemic rats.

Obese patients have an increased incidence of systemic infections and higher morbidity and mortality rates than normal weight subjects. Ghrelin is a potent orexigenic signal from the stomach and seems to play a role in the generation and control of immune interactions. To examine a possible benefit of a single ghrelin application on acute endotoxemia, chronic intravenous (i.

Laparoscopy vs minilaparotomy and full laparotomy preserves circulatory but not peritoneal and pulmonary immune responses.

Purpose: Laparoscopy has been associated with lower inflammatory responses. However, it has been postulated that minilaparotomy, in contrast to full laparotomy, is equally minimally invasive.

Objective: The aim of this study was to investigate local, systemic, and distant organ immune responses after different surgical approaches to the abdominal cavity, such as minilaparotomy, full laparotomy, and laparoscopy, in a small animal model.

The carina as a landmark for central venous catheter placement in small children.

Central venous devices are frequently used in children to monitor haemodynamic status, to administer fluids, medication, parenteral nutrition and for blood sampling. Life-threatening complications that may occur on insertion if the central venous catheter (CVC) is misplaced, are cardiac tamponade or a hydro-/haemopericardium. There is still controversy over the optimum catheter tip position in paediatric patients, whether to place the CVC tip in the superior vena cava, outside the pericardial boundaries or in the right atrium.

Perioperative normothermia depends on intraoperative warming procedure, extent of the surgical intervention and age of the experimental animal.

The maintenance of a physiological body temperature during and early after surgical interventions in experimental animals such as rodents is often neglected. Therefore the positive influence of an adequate use of warming blankets (WB) on the rectal body temperature in rats was investigated during two different surgical interventions, with a special focus on possible differences between young adult (2.5+/-0.

Hepatic leptin signaling in obesity.

Obesity, a state of apparent "leptin resistance" is well known to be associated with insulin resistance. In diet-induced obesity (DIO), hepatic insulin signaling is impaired but the link between leptin and insulin signaling pathways is only incompletely defined. The aim of the present study was to evaluate the effects of DIO on leptin and insulin cross-signaling in the liver.

Neuropeptide Y stabilizes body temperature and prevents hypotension in endotoxaemic rats.

The on-going high mortality from sepsis motivates continuous research for novel therapeutic strategies. Neuropeptide Y (NPY), a sympathetic neurotransmitter, has been shown to increase survival in experimental septic shock in rats. This protective effect might be due to immunological, cardiovascular or thermoregulatory effects.

Reduced tissue immigration of monocytes by neuropeptide Y during endotoxemia is associated with Y2 receptor activation.

Neuropeptide Y (NPY) increases survival in experimental septic shock, which might be mediated by cardiovascular and/or immunological effects. To study the latter hypothesis, we monitored blood leukocyte subsets over 96 h after intravenous (i.v.

Changes in cerebral endothelial barrier antigen, without alteration of permeability for intravenously injected leptin in diet-induced obesity in rats.

Leptin, a potent anorectic, 16-kDa, adipose tissue-derived protein, predominantly acts in hypothalamic nuclei, signaling obesity and modulating ingestive behavior. To reach this brain area, leptin, probably has to cross the blood-brain barrier (BBB). In some cases of obesity, enhanced leptin levels in the blood do not result in anorectic effects, probably due to an altered leptin transport across the BBB.