Search results for " injury"

C1-esterase inhibitor in ischemia and reperfusion.

2002

Summary Myocardial injury from ischemia can be aggravated by reperfusion of the jeopardized area. The precise underlying mechanisms have not been clearly defined, but proinflammatory events including complement activation play important roles. Cardioprotection by complement inhibition inter alia C1-esterase-inhibitor (C1-INH) was examined in several experimental models and under clinical conditions with ischemia and reperfusion. C1-INH reduced local anaphylatoxin release revealing the importance of the classical complement pathway. Inhibition of local complement activation was accompanied by improvement of myocardial function and perfusion of the previously ischemic myocardium. Leukocyte en…

Cardioprotection by gene therapy: A review paper on behalf of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of…

2015

Ischemic heart disease remains the leading cause of death worldwide. Ischemic pre-, post-, and remote conditionings trigger endogenous cardioprotection that renders the heart resistant to ischemic-reperfusion injury (IRI). Mimicking endogenous cardioprotection by modulating genes involved in cardioprotective signal transduction provides an opportunity to reproduce endogenous cardioprotection with better possibilities of translation into the clinical setting. Genes and signaling pathways by which conditioning maneuvers exert their effects on the heart are partially understood. This is due to the targeted approach that allowed identifying one or a few genes associated with IRI and cardioprote…

Computed tomography detects changes in contrast agent diffusion after collagen cross-linking typical to natural aging of articular cartilage

2011

SummaryObjectiveThe effect of threose-induced collagen cross-linking on the mechanical and diffusive properties of cartilage was investigated in vitro. In particular, we investigated the potential of Contrast Enhanced Computed Tomography (CECT) to detect changes in articular cartilage after increased collagen cross-linking, which is an age-related phenomenon.MethodsOsteochondral plugs (Ø=6.0mm, n=28) were prepared from intact bovine patellae (n=7). Two of the four adjacent samples, prepared from each patella, were treated with threose to increase the collagen cross-linking, while the other two specimen served as paired controls. One sample pair was mechanically tested and then mechanically …

Comparison of heparin to citrate as a catheter locking solution for non-tunneled central venous hemodialysis catheters in patients requiring renal re…

2014

Background The incidence of acute kidney injury (AKI) is estimated at 10 to 20% in patients admitted to intensive care units (ICU) and often requires renal replacement therapy (RRT). ICU mortality in AKI patients can exceed 50%. Venous catheters are the preferred vascular access method for AKI patients requiring RRT, but carry a risk of catheter thrombosis or infection. Catheter lock solutions are commonly used to prevent such complications. Heparin and citrate locks are both widely used for tunneled, long-term catheters, but few studies have compared citrate versus heparin for patients with short-term, non-tunneled catheters. We aim to compare citrate 4% catheter lock solution versus hepar…

Assessment of alterations in barrier functionality and induction of proinflammatory and cytotoxic effects after sulfur mustard exposure of an in vitr…

2007

Acute lung injury after sulfur mustard (SM) inhalation is characterized by massive, localized hemorrhage and alveolar edema, which implies severe disruption of the vascular and distal airway barrier. In this study, we tested a recently established in vitro coculture model of the alveolo-capillary barrier for its applicability to investigate acute toxic effects of SM at the human respiratory unit. The epithelial compartment of cocultures was exposed to varying concentrations of SM (0-1000 microM; t = 30 min). Following exposure, functional and structural barrier integrity of cocultures was monitored over a period of 24 h. A 50% reduction of transbilayer electrical resistance (TER) within 12-…

Central and Peripheral Secondary Cell Death Processes after Transient Global Ischemia in Nonhuman Primate Cerebellum and Heart

2019

Cerebral ischemia and its pathological sequelae are responsible for severe neurological deficits generally attributed to the neural death within the infarcted tissue and adjacent regions. Distal brain regions, and even peripheral organs, may be subject to more subtle consequences of the primary ischemic event which can initiate parallel disease processes and promote comorbid symptomology. In order to characterize the susceptibility of cerebellar brain regions and the heart to transient global ischemia (TGI) in nonhuman primates (NHP), brain and heart tissues were harvested 6 months post-TGI injury. Immunostaining analysis with unbiased stereology revealed significant cell death in lobule II…

Onset of heart failure determines the hepatic cell death pattern.

2011

Background and rationale. Acute and chronic heart failure (HF) may affect the liver, but the underlying mechanisms that lead to progressive liver damage are poorly understood. The hepatic cytokeratin-18 (CK18) epitopes M65 and M30 have been reported to distinguish between overall (necrotic) and apoptotic cell death, respectively. We aimed to evaluate the predominant hepatic cell death pattern in acute vs. chronic heart failure and examined if these assays predict the course of the disease. Main results. In a prospective study comprising 21 patients with acute HF (AHF) and 18 patients with chronic HF (CHF) serum levels of M65 and M30 were assessed. Compared with CHF, M65 levels were signific…

Destruction of Kupffer’s cells increases total liver blood flow and decreases ischemia reperfusion injury in pigs

2000

Pharmacological Suppression of CNS Scarring by Deferoxamine Reduces Lesion Volume and Increases Regeneration in an In Vitro Model for Astroglial-Fibr…

2015

Lesion-induced scarring is a major impediment for regeneration of injured axons in the central nervous system (CNS). The collagen-rich glial-fibrous scar contains numerous axon growth inhibitory factors forming a regeneration-barrier for axons. We demonstrated previously that the combination of the iron chelator 2,2'-bipyridine-5,5'-decarboxylic acid (BPY-DCA) and 8-Br-cyclic AMP (cAMP) inhibits scar formation and collagen deposition, leading to enhanced axon regeneration and partial functional recovery after spinal cord injury. While BPY-DCA is not a clinical drug, the clinically approved iron chelator deferoxamine mesylate (DFO) may be a suitable alternative for anti-scarring treatment (A…

Innate and adaptive immune responses in the CNS.

2015

Almost every disorder of the CNS is said to have an inflammatory component, but the precise nature of inflammation in the CNS is often imprecisely defined, and the role of CNS-resident cells is uncertain compared with that of cells that invade the tissue from the systemic immune compartment. To understand inflammation in the CNS, the term must be better defined, and the response of tissue to disturbances in homoeostasis (eg, neurodegenerative processes) should be distinguished from disorders in which aberrant immune responses lead to CNS dysfunction and tissue destruction (eg, autoimmunity). Whether the inflammatory tissue response to injury is reparative or degenerative seems to be depende…