58 research outputs found
Creating transplant tolerance by taming adverse intragraft innate immunity
Certain forms of inflammation of an allograft are highly detrimental to the induction and maintenance of transplant tolerance as they foster stable commitment to graft-destructive, not graft-protective, forms of T-cell immunity. Hence, a reduction in adverse tissue inflammation may prove crucial in facilitating the induction and maintenance of a long-lasting state of transplant tolerance
The Role of TNF-α in Mice with Type 1- and 2- Diabetes
Background: Previously, we have demonstrated that short-term treatment of new onset diabetic Non-obese diabetic (NOD) mice, mice that are afflicted with both type 1 (T1D) and type 2 (T2D) diabetes with either Power Mix (PM) regimen or alpha1 antitrypsin (AAT) permanently restores euglycemia, immune tolerance to self-islets and normal insulin signaling. Methodology and Principal Findings: To search for relevant therapeutic targets, we have applied genome wide transcriptional profiling and systems biology oriented bioinformatics analysis to examine the impact of the PM and AAT regimens upon pancreatic lymph node (PLN) and fat, a crucial tissue for insulin dependent glucose disposal, in new onset diabetic non-obese diabetic (NOD) mice. Systems biology analysis identified tumor necrosis factor alpha (TNF-) as the top focus gene hub, as determined by the highest degree of connectivity, in both tissues. In PLNs and fat, TNF- interacted with 53% and 32% of genes, respectively, associated with reversal of diabetes by previous treatments and was thereby selected as a therapeutic target. Short-term anti-TNF- treatment ablated a T cell-rich islet-invasive and beta cell-destructive process, thereby enhancing beta cell viability. Indeed anti-TNF- treatment induces immune tolerance selective to syngeneic beta cells. In addition to these curative effects on T1D anti-TNF-e33254 treatment restored in vivo insulin signaling resulting in restoration of insulin sensitivity. Conclusions: In short, our molecular analysis suggested that PM and AAT both may act in part by quenching a detrimental TNF- dependent effect in both fat and PLNs. Indeed, short-term anti-TNF- mAb treatment restored enduring euglycemia, self-tolerance, and normal insulin signaling
Standard Sedation and Sedation With Isoflurane in Mechanically Ventilated Patients With Coronavirus Disease 2019
Adaptive changes of the microvasculature in the experimental murine colitis = (Adaptive Veränderungen der Mikrovaskularisation bei der experimentellen murinen Kolitis)
Use of anaesthesia machines for mechanical ventilation and sedation in patients with COVID-19 ARDS
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More of the Gut in the Lung: How Two Microbiomes Meet in ARDS
In critically ill patients, lung and gut microbiomes undergo profound changes. Lung microbiome might become enriched with gut-associated microbes as recently demonstrated in sepsis and acute respiratory distress syndrome (ARDS). It has been proposed that in these conditions, bacteria from the gut might enter the lungs via translocation, a process facilitated by increased gut and alveolo-capillary permeability. In patients requiring mechanical ventilation after severe trauma, lung microbiome enrichment with gut-associated microbes was found to correlate with the development of ARDS. The lungs in ARDS are increasingly susceptible to opportunistic infections which can further perpetuate alveolar inflammation and injury. Undoubtedly, more research on the gut-lung crosstalk in critically ill patients is needed to identify causal relationships between the altered microbiome, infections, inflammation, and acute lung injury. With further insights, this area of investigation could lead to the development of novel, microbiome-targeted, and immunomodulation strategies with the potential to improve outcomes of critically ill patients with sepsis, trauma, and ARDS
The Use of Analgesia and Sedation in Mechanically Ventilated Patients With COVID-19 Acute Respiratory Distress Syndrome
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Back to the Future: Evidence-Based Sedation Practices in the ICU?
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