Hepatic ischemia-reperfusion injury (IRI) is a multifactorial phenomenon which has been associated with adverse clinical outcomes. IRI related tissue damage is characterized by various chronological events depending on the experimental model or clinical setting. Despite the fact that IRI research has been in the spotlight of scientific interest for over three decades with a significant and continuous increase in publication activity over the years and the large number of pharmacological and surgical therapeutic attempts introduced, not many of these strategies have made their way into everyday clinical practice. Furthermore, the pathomechanism of hepatic IRI has not been fully elucidated yet. In the complex process of the IRI, flow properties of blood are not neglectable. Hemorheological factors play an important role in determining tissue perfusion and orchestrating mechanical shear stress-dependent endothelial functions. Antioxidant and anti-inflammatory agents, ischemic conditioning protocols, dynamic organ preservation techniques may improve rheological properties of the post-reperfusion hepatic blood flow and target endothelial cells, exerting a potent protection against hepatic IRI. In this review paper we give a comprehensive overview of microcirculatory, rheological and molecular–pathophysiological aspects of hepatic circulation in the context of IRI and hepatoprotective approaches.

Rapidly progressing mucosal breakdown limits the intestinal preservation time below 10 h. Recent studies indicate that intraluminal solutions containing polyethylene glycol (PEG) alleviate preservation injury of intestines stored in UW-Viaspan. We investigated whether a low-sodium PEG solution is beneficial for intestines stored in histidine-tryptophane-ketoglutarate (HTK) preservation solution. Rat intestines used as control tissue (group 1) were perfused with HTK, groups 2 and 3 received either a customized PEG-3350 (group 2) or an electrolyte solution (group 3) intraluminally before cold storage. Tissue injury, brush-border maltase activity, zonula occludens-1 (ZO-1) and claudin-3 expression in the tight junctions (TJ) were analyzed after 8, 14 and 20 h. We measured epithelial resistance and permeability (Ussing chamber) after 8 and 14 h. Group 2 had superior morphology while maltase activity was similar in all groups. TJ proteins rapidly decreased and decolocalized in groups 1 3; these negative events were delayed in group 2, where colocalization persisted for about 14 h. Intestines in group 2 had higher epithelial resistance and lower permeability than the other groups. These results suggest that a customized PEG solution intraluminally reduces the intestinal preservation injury by improving several major epithelial characteristics without negatively affecting the brush-border enzymes or promoting edema.

Background.: Solid organ transplant (SOT) recipients may be more vulnerable to coronavirus disease 2019 (COVID-19). Data on the clinical course of COVID-19 in immunosuppressed patients are limited, and the optimal management strategy for these patients is yet unclear. Methods.: We present 53 SOT recipients (31 kidney transplant recipients, 8 liver transplant recipients, 5 heart transplant recipients, 5 lung transplant recipients, 3 liver-kidney transplant recipients, and 1 kidney-after-heart transplant recipient), transplanted at a Swedish high-volume transplant center and each diagnosed with COVID-19 between February 21, 2020 and June 22, 2020. Demographic, clinical, and treatment data were extracted from the electronic patient files. Results.: Patients reported fever (61%), cough (43%), diarrhea (31%), and upper respiratory symptoms (29%). The median age was 56 years, and 57% were male. According to severity, 55% had mild, 13% had moderate, 19% had severe, and 13% had critical disease. Thirty-seven patients (70%) were hospitalized, with 8 requiring intensive care. Thirteen of the 37 patients were initially managed as outpatients but later hospitalized. One patient received hydroxychloroquine, and no patients received antivirals. Antimetabolites and calcineurin inhibitors were held or reduced in two-thirds. Twenty-seven of 37 hospitalized patients (73%) received low-molecular-weight heparin. Five (13.5%) hospitalized patients died. Overall survival for the entire cohort was 90.5%. No rejection episodes were noted. Conclusions.: Hospitalization, lowering of immunosuppression, and prophylactic anticoagulation were the most common therapeutic interventions for SOT recipients with COVID-19. A significant proportion of patients could be managed on an outpatient basis, while keeping a low threshold for admission. Mild and moderate disease forms seem to have a good outcome.

Mast Cells (MCs) play a role in immune responses and more recently MCs have been involved in tumoral angiogenesis. In particular MCs can release tryptase, a potent in vivo and in vitro pro-angiogenic factor via proteinase-activated receptor-2 (PAR-2) activation and mitogen-activated protein kinase (MAPK) phosphorylation. MCs can release tryptase following c-Kit receptor activation. Nevertheless, no data are available concerning the relationship among MCs Density Positive to Tryptase (MCDPT) and Microvascular Density (MVD) in both primary gastric cancer tissue and loco-regional lymph node metastases. A series of 75 GC patients with stage T_2–3N_2–3M₀ (by AJCC for Gastric Cancer Seventh Edition) undergone to radical surgery were selected for the study. MCDPT and MVD were evaluated by immunohistochemistry and by image analysis system and results were correlated each to other in primary tumor tissue and in metastatic lymph nodes harvested. Furthermore, tissue parameters were correlated with important clinico-pathological features. A significant correlation between MCDPT and MVD was found in primary gastric cancer tissue and lymph node metastases. Pearson t-test analysis (r ranged from 0.74 to 0.79; p-value ranged from 0.001 to 0.003). These preliminary data suggest that MCDPT play a role in angiogenesis in both primary tumor and in lymph node metastases from GC. We suggest that MCs and tryptase could be further evaluated as novel targets for anti-angiogenic therapies.

Coronavirus disease 2019 (COVID-19) ranges from a mild illness to acute respiratory distress syndrome (ARDS), multiorgan dysfunction, and death. Transplant recipients are vulnerable due to comorbid...

Ischemia-reperfusion injury is the leading cause of acute kidney injury in a variety of clinical settings such as renal transplantation and hypovolemic and/or septic shock. Strategies to reduce ischemia-reperfusion injury are obviously clinically relevant. Ischemic conditioning is an inherent part of the renal defense mechanism against ischemia and can be triggered by short periods of intermittent ischemia and reperfusion. Understanding the signaling transduction pathways of renal ischemic conditioning can promote further clinical translation and pharmacological advancements in this era. This review summarizes research on the molecular mechanisms underlying both local and remote ischemic pre-, per- and postconditioning of the kidney. The different types of conditioning strategies in the kidney recruit similar powerful pro-survival mechanisms. Likewise, renal ischemic conditioning mobilizes many of the same protective signaling pathways as in other organs, but differences are recognized.