Cascading renal injury after brain death: Unveiling glycocalyx alteration and the potential protective role of tacrolimus.

Brain death (BD) is a complex medical state that triggers systemic disturbances and a cascade of pathophysiological processes. This condition significantly impairs both kidney function and structural integrity, thereby presenting considerable challenges to graft viability and the long-term success of transplantation endeavors. Tacrolimus (FK506), an immunosuppressive drug, was used in this study to assess its impact as a pretreatment on brain death-induced renal injury.

HIGH-MOLECULAR-WEIGHT HYALURONAN-A POTENTIAL ADJUVANT TO FLUID RESUSCITATION IN ABDOMINAL SEPSIS?

While fluid resuscitation is fundamental in the treatment of sepsis-induced tissue hypoperfusion, a sustained positive fluid balance is associated with excess mortality. Hyaluronan, an endogenous glycosaminoglycan with high affinity to water, has not been tested previously as adjuvant to fluid resuscitation in sepsis. In a prospective, parallel-grouped, blinded model of porcine peritonitis sepsis, we randomized animals to intervention with adjuvant hyaluronan (add-on to standard therapy, n = 8) or 0.

Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis.

Plasma hyaluronan (HA) increases systemically in type 2 diabetes (T2D) and the HA synthesis inhibitor, 4-Methylumbelliferone, has been proposed to treat the disease. However, HA is also implicated in normal physiology. Therefore, we generated a Hyaluronan Synthase 2 transgenic mouse line, driven by a tet-response element promoter to understand the role of HA in systemic metabolism.

Abundance and size of hyaluronan in naked mole-rat tissues and plasma.

Large amounts of ultra-high molecular weight hyaluronan (HA) have been described as the main cause of cancer resistance in naked mole-rats (Heterocephalus glaber, NMR). Our work examined HA metabolism in these rodents more closely. HA was localized and quantified using HA binding proteins.

Endothelial Glycocalyx Impairment in Disease: Focus on Hyaluronan Shedding.

Hyaluronan (HA) is a ubiquitous glycosaminoglycan of the extracellular matrix. It is present in the endothelial glycocalyx covering the apical surface of endothelial cells. The endothelial glycocalyx regulates blood vessel permeability and homeostasis.

Endothelial Glycocalyx as a Shield Against Diabetic Vascular Complications: Involvement of Hyaluronan and Hyaluronidases.

The endothelial glycocalyx (EG), which covers the apical surface of the endothelial cells and floats into the lumen of the vessels, is a key player in vascular integrity and cardiovascular homeostasis. The EG is composed of PGs (proteoglycans), glycoproteins, glycolipids, and glycosaminoglycans, in particular hyaluronan (HA). HA seems to be implicated in most of the functions described for EG such as creating a space between blood and the endothelium, controlling vessel permeability, restricting leukocyte and platelet adhesion, and allowing an appropriate endothelial response to flow variation through mechanosensing.

Hyaluronidase 1 Deficiency Preserves Endothelial Function and Glycocalyx Integrity in Early Streptozotocin-Induced Diabetes.

Hyaluronic acid (HA) is a major component of the glycocalyx involved in the vascular wall and endothelial glomerular permeability barrier. Endocytosed hyaluronidase HYAL1 is known to degrade HA into small fragments in different cell types, including endothelial cells. In diabetes, the size and permeability of the glycocalyx are altered.

Deficiency in mouse hyaluronidase 2: a new mechanism of chronic thrombotic microangiopathy.

Hyaluronan is a major component of the extracellular matrix and glycocalyx. Its main somatic degrading enzymes are hyaluronidases 1 and 2, neither of which is active in the bloodstream. We generated hyaluronidase 2-deficient mice.

Subcellular trafficking and activity of Hyal-1 and its processed forms in murine macrophages.

The hyaluronidase Hyal-1 is an acid hydrolase that degrades hyaluronic acid (HA), a component of the extracellular matrix. It is often designated as a lysosomal protein. Yet few data are available on its intracellular localization and trafficking.

Identification, cloning, and expression of the Scytalidium acidophilum XYL1 gene encoding for an acidophilic xylanase.

We cloned XYL1, a Scytalidium acidophilum gene encoding for an acidophilic family 11 xylanase. The XYL1p protein was expressed in Pichia pastoris using the pPICZalphaA expression plasmid. The secreted protein was purified by TAXI affinity column chromatography.

Impaired accumulation of granulocytes in the lung during ozone adaptation.

Respiratory alterations induced by an acute exposure to ozone (O(3)) paradoxically resolve during multiday exposure. This adaptation is characteristically accompanied by a gradual attenuation of lung neutrophilia. As maintenance of neutrophilia at the site of inflammation is due to cytokine-mediated delayed neutrophil apoptosis, which is associated with reduced levels of Bax, a proapoptotic protein, we sought to determine whether defects in these mechanisms could account for O(3) adaptation.

Enhanced survival of lung granulocytes in an animal model of asthma: evidence for a role of GM-CSF activated STAT5 signalling pathway.

Background: As granulocyte/macrophage colony stimulating factor (GM-CSF) mediated delay of granulocyte apoptosis contributes to the accumulation of inflammatory cells at the site of inflammation in many diseases, we sought to determine whether asthma is also associated with a GM-CSF dependent increase in lung granulocyte survival. Moreover, because GM-CSF mediates its effects through activation of signal transducer and activator of transcription 5 (STAT5), we also investigated the potential role of STAT5 in allergic inflammation.

Methods: Blood granulocytes were recovered from six healthy and six heaves affected horses, a model of asthma.

p65 Homodimer activity in distal airway cells determines lung dysfunction in equine heaves.

Nuclear factor-kappaB (NF-kappaB) activity, which is a key regulator of inflammatory gene expression, is increased in bronchial epithelial cells from horses suffering from heaves (a hypersensitivity-associated inflammatory condition of the lung). To determine whether this increased activity extends to distal airways and to other pulmonary cells, cells recovered by broncho-alveolar lavage (BAL) in healthy and heaves-affected horses were assessed for NF-kappaB activity. NF-kappaB activity was much higher in BAL cells from heaves-affected horses, especially during crisis (disease exacerbation), than in cells from healthy horses.

Comparison of inulin with urea as dilutional markers of bronchoalveolar lavage in healthy and heaves-affected horses.

Solute analysis in bronchoalveolar lavage fluid involves the use of dilutional markers to correct for variable recovery of pulmonary epithelial lining fluid (PELF). Urea is the best characterised endogenous marker, whereas inulin appears to meet the requirements of an exogenous marker. In horses, the use of inulin has never been investigated and the impact of lower airway diseases such as heaves, on PELF recovery is unknown.

Mechanisms of persistent NF-kappa B activity in the bronchi of an animal model of asthma.

In most cells trans-activating NF-kappaB induces many inflammatory proteins as well as its own inhibitor, IkappaB-alpha, thus assuring a transient response upon stimulation. However, NF-kappaB-dependent inflammatory gene expression is persistent in asthmatic bronchi, even after allergen eviction. In the present report we used bronchial brushing samples (BBSs) from heaves-affected horses (a spontaneous model of asthma) to elucidate the mechanisms by which NF-kappaB activity is maintained in asthmatic airways.