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The authors found that HSCT recipients of grafts carrying the -1082GG interleukin-10 (IL-10) gene promoter region variant had a three-fold lower incidence of grade II-IV acute GVHD compared to IL-10 -1082AA graft recipients. Immunologic complications following organ, cell, or tissue transplantation still raise significant challenges related to their diagnosis and treatment. The pre-transplant crossmatch test between donor cells and recipient sera developed by Terasaki in the mid-1960s has allowed for better organ allocation and reduced immunologic risks after transplantation at a time when immunosuppressive medication was in its infancy. In spite of an increased understanding of transplant immunobiology and the availability of effective immunosuppression, acute rejection or graft-versus-host disease (GVHD) still occur in up to 50% of transplant recipients, depending on the graft type [[1]]. [Extracted from the article]

Intestinal transplantation (ITx) remains a lifesaving option for patients suffering from irreversible intestinal failure and complications from total parenteral nutrition. Since its inception, it became obvious that intestinal grafts are highly immunogenic, due to their high lymphoid load, the abundance in epithelial cells and constant exposure to external antigens and microbiota. This combination of factors and several redundant effector pathways makes ITx immunobiology unique. To this complex immunologic situation, which leads to the highest rate of rejection among solid organs (>40%), there is added the lack of reliable non-invasive biomarkers, which would allow for frequent, convenient and reliable rejection surveillance. Numerous assays, of which several were previously used in inflammatory bowel disease, have been tested after ITx, but none have shown sufficient sensibility and/or specificity to be used alone for diagnosing acute rejection. Herein, we review and integrate the mechanistic aspects of graft rejection with the current knowledge of ITx immunobiology and summarize the quest for a noninvasive biomarker of rejection. [ABSTRACT FROM AUTHOR]

Determining the author of a text is a difficult task. Here, we compare multiple Artificial Intelligence techniques for classifying literary texts written by multiple authors by taking into account a limited number of speech parts (prepositions, adverbs, and conjunctions). We also introduce a new dataset composed of texts written in the Romanian language on which we have run the algorithms. The compared methods are artificial neural networks, multi-expression programming, k-nearest neighbour, support vector machines, and decision trees with C5.0. Numerical experiments show, first of all, that the problem is difficult, but some algorithms are able to generate acceptable error rates on the test set. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is frequent after liver transplantation (LT) and correlates with later development of chronic kidney disease. Its etiology is multifactorial and combines pre-, intra-, and postoperative factors. Additionally, the liver graft itself seems an important element in the development of AKI, yet the detailed mechanisms remain unclear. We hypothesized that grafts of LT recipients developing significant early AKI may show distinct proteomic alterations, and we set out to identify proteome differences between LT recipients developing moderate or severe AKI (n = 7) and LT recipients without early renal injury (n = 7). Liver biopsies obtained one hour after reperfusion were assessed histologically and using quantitative proteomics. Several cytokines and serum amyloid A2 (SAA2) were analyzed in serum samples obtained preoperatively, 2–4 h, and 20–24 h after graft reperfusion, respectively. LT induced mild histological alterations without significant differences between groups but uniformly altered liver function tests peaking on postoperative day 1, with a trend towards more severe alterations in patients developing AKI. Global quantitative proteomic analysis revealed 136 proteins differing significantly in their expression levels (p < 0.05, FC 20%): 80 proteins had higher and 56 had lower levels in the AKI group. Most of these proteins were related to immune and inflammatory responses, host defense, and neutrophil degranulation. No differences between the studied pro- and anti-inflammatory cytokines or SAA2 between groups were found at any moment. Our results suggest that grafts of LT patients who develop early AKI reveal a distinct proteome dominated by an early yet prominent activation of the innate immunity. These findings support the hypothesis that AKI after LT may be favored by certain graft characteristics. [ABSTRACT FROM AUTHOR]

• During COVID-19, organ transplant recipients have developed all forms of the disease. • This Romanian centre has a higher prevalence but similar outcomes as other European centres. • Excellent patient and graft short-term outcomes were found in those with mild and moderate COVID-19. • Targeted antiviral therapies do not seem to impair kidney graft function. The lack of effective treatments for coronavirus disease 2019 (COVID-19) has mandated the repurposing of several drugs, including antiretrovirals and remdesivir (RDV). These compounds may induce acute kidney injury and are not recommended in patients with poor renal function, such as kidney transplant (KTx) recipients. The records of 42 KTx recipients with COVID-19 were reviewed. Some of them were receiving antiretrovirals (n = 10) or RDV (n = 8) as part of COVID-19 management. Most patients were male (71%) and their median age was 52 years. The median glomerular filtration rate in these patients was 56 ml/min. Regarding disease severity, 36% had mild disease, 19% had moderate disease, 31% had severe disease, and 12% had critical disease. Subgroups, i.e., patients receiving antiretrovirals, RDV, or no antivirals, were comparable in terms of patient age, comorbidities, and immunosuppression. Seven patients (16.6%) died during hospitalization. Acute kidney injury was found in 24% of KTx recipients at admission. Upon discharge, estimated glomerular filtration rate (eGFR) increased in 32% and decreased in 39% of the KTx recipients compared with the admission rate. The decrease was more prevalent in the RDV group (80%) compared with KTx recipients without any antiviral treatment (29%) (p < 0.05). Most patients (62%) returned to baseline eGFR values within 1 month of discharge. The proportion was similar between the patients receiving antiviral treatment and those not receiving this treatment. KTx recipients run a high risk of COVID-19-related renal impairment. Antivirals appear to be safe for use without major risks for kidney injury. [ABSTRACT FROM AUTHOR]

Intestinal transplantation (ITx) is a lifesaving procedure for complicated intestinal failure. Specifically for the intestine, IGL-1 demonstrated improved graft viability and epithelial repair compared to UW in animal experimental models [6]. Seven multivisceral and six isolated intestinal grafts were transplanted. [Extracted from the article]

Background. Exogenous bilirubin may reduce experimental ischemia-reperfusion injury (IRI) due to its antioxidant properties. We studied if early graft exposure to high bilirubin levels in the recipient affects the early IRI and outcomes after liver transplantation (LTx). Methods. In 427 LTx patients, the AUROC curve based on bilirubin and AST at day 1 identified a cutoff of 2.04 mg/dL for the recipient pretransplant bilirubin. Recipients were grouped as having low (group L, n=152) or high (group H, n=275) bilirubin. Both groups had similar donor-related variables (age, preservation time, donor BMI > 28, and donor risk index (DRI)). Results. Alanine (ALT) and aspartate (AST) aminotransferase levels were higher in group L at day 1; ALT levels remained higher at day 2 in group L. LTx from high risk donors (DRI > 2) revealed a trend towards lower transaminases during the first two days after transplantation in group H. One month and 1-year patient survival were similar in groups L and H. High preoperative bilirubin did not affect the risk for early graft dysfunction (EGD), death, or graft loss during the first year after transplantation nor the incidence of acute rejection. LTx using donors with DRI > 2 resulted in similar rates of EGD in both groups. Conclusion. Increased bilirubin appears to reduce the early IRI after LTx yet this improvement was insufficient to improve the clinical outcome. [ABSTRACT FROM AUTHOR]

Genetic Programming (GP) is an automated method for creating computer programs starting from a high-level description of the problem to be solved. Many variants of GP have been proposed in the recent years. In this paper we are reviewing the main GP variants with linear representation. Namely, Linear Genetic Programming, Gene Expression Programming, Multi Expression Programming, Grammatical Evolution, Cartesian Genetic Programming and Stack-Based Genetic Programming. A complete description is provided for each method. The set of applications where the methods have been applied and several Internet sites with more information about them are also given. [ABSTRACT FROM AUTHOR]

A complex model for evolving the update strategy of a Particle Swarm Optimisation (PSO) algorithm is described in this paper. The model is a hybrid technique that combines a Genetic Algorithm (GA) and a PSO algorithm. Each GA chromosome is an array encoding a meaning for updating the particles of the PSO algorithm. The Evolved PSO algorithm is compared to several human-designed PSO algorithms by using ten artificially constructed functions and one real-world problem. Numerical experiments show that the Evolved PSO algorithm performs similarly and sometimes even better than the Standard approaches for the considered problems. The Evolved PSO is highly scalable (regarding the size of the problem's input), being able to solve problems having different dimensions. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "P-NGAL Day 1 predicts early but not one year graft function following deceased donor kidney transplantation–The CONTEXT study." The correction states that there is an error in Table 4 of the article, where the estimated glomerular filtration (eGFR) values were calculated using an incorrect version of the MDRD-formula. The correct reference for the study is also provided. The document includes a graph and a table showing correlations between biomarkers or urine output measured on Day 1 and kidney graft function at three and twelve months. The authors of the article are Marie B. Nielsen, Nicoline V. Krogstrup, Gertrude J. Nieuwenhuijs-Moeke, Mihai Oltean, Frank J. M. F. Dor, Bente Jespersen, and Henrik Birn. [Extracted from the article]

Decellularized tissue is generally considered immune privileged after transplantation and is an attractive scaffold type for tissue regeneration, including applications for infertility treatment. However, the immune response following transplantation of decellularized tissue is insufficiently studied, in particular after they have been recellularized with mesenchymal stem cells (MSCs). Therefore, we replaced a large uterus segment with a bioengineered graft developed from decellularized uterus tissue and analyzed the immune response during the first 4 months in acellular or MSCs-recellularized scaffolds in the rat. Immunohistochemistry-stained infiltrating immune cells and plasma levels for 16 cytokines and chemokines were quantified. Results revealed that MSCs created an advantageous microenvironment by increasing anti-inflammatory interleukin 10 levels, and increasing the population of FOXP3+ TRegs and CD163+ M2 macrophages, and by reducing the CD8+ cytotoxic T cell population. Hence, MSCs should be considered an immunotherapeutic cell source with the ability to dictate regeneration success after decellularized tissue transplantation. [ABSTRACT FROM AUTHOR]

• Studies on remdesivir as COVID-19 therapy excluded patients with poor renal function • Kidney transplant recipients frequently have impaired renal function • No negative effect on the renal function was seen after 5 days of remdesivir • Remdesivir significantly improved intensive care survival • Remdesivir did not seem to reduce overall mortality The aim of the study was to evaluate the impact of remdesivir on overall mortality, ICU mortality, and renal functional outcome in hospitalized patients with COVID-19 who received kidney transplant. We reviewed 165 patients with KTx hospitalized owing to COVID-19 between March 1, 2020, and May 31, 2021. A total of 38 patients with KTx received a 5-day RDV treatment, whereas 127 received standard of care (SOC). Overall and ICU mortality along with functional outcome were assessed. The 2 groups had similar baseline characteristics. RDV treatment was completed in all patients without any adverse effects attributable to RDV. In terms of overall mortality, there was no difference between the RDV and SOC groups (18% vs 23%, p >0.05), but the ICU mortality was significantly reduced in the RDV group (39% vs 83%, p <0.05). RDV seems to have no nephrotoxic effect on patients with KTx because there was no difference in the incidence of AKI between RDV and SOC groups (50% vs 43%, p >0.05), and the discharge eGFR values significantly improved in the RDV group compared with the admission values (57 ± 23 vs 44 ± 22, p <0.05). Five-day RDV treatment appears safe in KTx recipients, and without obvious nephrotoxic effects. Also, RDV may decrease ICU mortality attributed to COVID-19. [ABSTRACT FROM AUTHOR]

Decellularized tissue is generally considered immune privileged after transplantation and is an attractive scaffold type for tissue regeneration, including applications for infertility treatment. However, the immune response following transplantation of decellularized tissue is insufficiently studied, in particular after they have been recellularized with mesenchymal stem cells (MSCs). Therefore, we replaced a large uterus segment with a bioengineered graft developed from decellularized uterus tissue and analyzed the immune response during the first 4 months in acellular or MSCs-recellularized scaffolds in the rat. Immunohistochemistry-stained infiltrating immune cells and plasma levels for 16 cytokines and chemokines were quantified. Results revealed that MSCs created an advantageous microenvironment by increasing anti-inflammatory interleukin 10 levels, and increasing the population of FOXP3+ TRegs and CD163+ M2 macrophages, and by reducing the CD8+ cytotoxic T cell population. Hence, MSCs should be considered an immunotherapeutic cell source with the ability to dictate regeneration success after decellularized tissue transplantation. [ABSTRACT FROM AUTHOR]

Summary: Although it is known that solid organ transplant recipients fare worse after COVID‐19 infection, data on the impact of COVID‐19 on clinical outcomes and allograft function in lung transplant (LTx) recipients are limited and based mainly on reports with short follow‐up. In this nationwide study, all LTx recipients with COVID‐19 diagnosed from 1 February 2020 to 30 April 2021 were included. The patients were followed until 1 August 2021 or death. We analysed demographics, clinical features, therapeutic management and outcomes, including lung function. Forty‐seven patients were identified: median age was 59 (10–78) years, 53.1% were male, and median follow‐up was 194 (23–509) days. COVID‐19 was asymptomatic or mild at presentation in 48.9%. Nine patients (19.1%) were vaccinated pre‐COVID infection. Two patients (4.3%) died within 28 days of testing positive, and the overall survival rate was 85.1%. The patients with asymptomatic or mild symptoms had a higher median % expected forced expiratory volume during the first second than the patients with worse symptoms (P = 0.004). LTx recipients develop the entire spectrum of COVID‐19, and in addition to previously acknowledged risk factors, lower pre‐COVID lung function was associated with more severe disease presentation. [ABSTRACT FROM AUTHOR]

Inflammation resulting from ischaemia/reperfusion injury can cause kidney graft dysfunction, increase the risk of delayed graft function and possibly reduce long‐term graft survival. Remote ischaemic conditioning may protect against ischaemia/reperfusion injury and mitigate the immunological response to the graft. We investigated the immunological effects of remote ischaemic conditioning on kidney transplantation from deceased donors in the randomized CONTEXT study. Three circulating dendritic cell (DC) subtypes identified in peripheral blood from kidney transplant recipients [myeloid DCs, plasmacytoid DCs and immunoglobulin‐like transcript (ILT)3+ DCs] were measured at baseline, days 1, 3 and 5 and 1 and 3 months after transplantation. We also quantified 21 cytokines at baseline, days 1 and 5 and 3 months after transplantation. Neither DC counts nor cytokine levels differed between patients receiving remote ischaemic conditioning and controls; however, several parameters exhibited dynamic and parallel alterations in the two groups over time, reflecting the immunological response to the kidney transplantation and immunosuppression. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the authors discuss various reports within the issue on topics including optical multiplexing techniques for photonic Clos networks in high performance computing architecture, optical spatial image processing and on how lossless logic systems could be built.

Background: Ischaemia-reperfusion injury in kidney transplantation leads to delayed graft function (DGF), which is associated with reduced long term graft function. Remote ischaemic conditioning (RIC) improved early kidney graft function in a porcine model of donation after brain death and was associated with improved long-term cardiac outcome after myocardial ischaemia. This randomised, double-blinded trial evaluated the effect of RIC on kidney graft outcome in the first year, and examined the predictive value of a new measure of initial kidney graft function, i.e. the estimated time to a 50% reduction in plasma creatinine post-transplantation (tCr50). Methods: A total of 225 patients undergoing deceased donor kidney transplantation were randomised to RIC or a sham procedure performed prior to kidney reperfusion. Up to four repetitive cycles of five minutes of leg ischaemia and five minutes of reperfusion were given. GFR, plasma creatinine, cystatin C and neutrophil gelatinase associated lipocalin (NGAL) were measured at three and twelve months and estimated GFR was calculated using four different equations. Other secondary outcomes were identified from patient files. Results: RIC did not affect GFR or other outcomes when compared to the sham procedure at three or twelve months. tCr50 correlated with one year graft function (p<0.0001 for both mGFR and eGFR estimates). In contrast, DGF i.e. "need of dialysis the first week" did not correlate significantly with one year GFR. Conclusion: RIC during deceased donor kidney transplantation did not improve one year outcome. However, tCr50 may be a relevant marker for studies aiming to improve graft onset. Trial registration: www.ClinicalTrials.gov Identifier: NCT01395719. [ABSTRACT FROM AUTHOR]

Introduction: Uterus transplantation has recently proved that infertility in women with uterine factor infertility can be cured. It is still an experimental procedure with numerous critical details remaining to be established, including tolerance to warm and cold ischemic insults. In preparation for human uterus transplantation trials, most teams use the sheep as a model system for research and team training, since the vasculature and the uterus is of similar size as in the human. We, therefore, aimed to develop an ex vivo sheep uterus reperfusion platform that mimics the reperfusion situation so that initial assessments and comparisons can be performed without the need for costly and labor‐intensive in vivo transplantation experiments. Material and methods: Isolated sheep uteri were perfused with the preservation solution IGL‐1 and were then exposed to cold ischemia for either 4 (n = 6) or 48 hours (n = 7). Uteri were then reperfused for 48 hours under normothermic conditions with an oxygenated recirculating perfusate containing growth factors and synthetic oxygen carriers. Histological and biochemical analysis of the perfusate was conducted to assess reperfusion injury. Results: Quantification of cell density indicated no significant edema in the myometrium or in the endometrium of uteri exposed to 4 hours cold ischemia and then a normothermic ex vivo reperfusion for 48 hours. Only the outer serosa layer and the inner columnar luminal epithelial cells were affected by the reperfusion. However, a much faster and severe reperfusion damage of all uterine layers were evident during the reperfusion experiment following 48 hours of cold ischemia. This was indicated by major accumulation of extracellular fluid, presence of apoptotic‐labeled glandular epithelial layer and vascular endothelium. A significant accumulation of lactate was measured in the perfusate with a subsequent decrease in pH. Conclusions: We developed a novel ex vivo sheep uterus model for prolonged perfusion. This model proved to be able to distinguish reperfusion injury‐related differences associated to organ preservation. The experimental setup is a platform that can be used to conduct further studies on uterine ischemia‐ and reperfusion injury that may lead to improved human uterus transplantation protocols. [ABSTRACT FROM AUTHOR]

Background: Early markers to predict delayed kidney graft function (DGF) may support clinical management. We studied the ability of four biomarkers (neutrophil gelatinase associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), cystatin C, and YKL-40) to predict DGF after deceased donor transplantation, and their association with early graft function and GFR at three and twelve months. Methods: 225 deceased donor kidney transplant recipients were included. Biomarkers were measured using automated assays or ELISA. We calculated their ability to predict the need for dialysis post-transplant and correlated with the estimated time to a 50% reduction in plasma creatinine (tCr50), measured glomerular filtration rate (mGFR) and estimated GFR (eGFR). Results: All biomarkers measured at Day 1, except urinary L-FABP, significantly correlated with tCr50 and mGFR at Day 5. Plasma NGAL at Day 1 and a timed urine output predicted DGF (AUC = 0.91 and AUC 0.98). Nil or only weak correlations were identified between early biomarker levels and mGFR or eGFR at three or twelve months. Conclusion: High plasma NGAL at Day 1 predicts DGF and is associated with initial graft function, but may not prove better than P-creatinine or a timed urine output. Early biomarker levels do not correlate with one-year graft function. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

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 T2-3N2-3M0 (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. [ABSTRACT FROM AUTHOR]

Introduction: Resistin is a pro-inflammatory adipokine that increases after brain injury (trauma, bleeding) and may initiate an inflammatory response. Resistin was found increased in deceased, brain dead organ donors (DBD) and correlated with delayed graft function after kidney transplantation. The kinetics of resistin during brain death (BD), its impact on the inflammatory response and the influence of several donor variables on resistin levels are still unknown. Methods: Resistin along with a panel of Th1/Th2 cytokines [interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL10, IL-12, IL-13 and tumor necrosis factor (TNF)] was analyzed in 36 DBDs after the diagnosis of BD and before organ procurement and in 12 living kidney donors (LD). The cytokine levels and resistin were analyzed in relation to donor parameters including cause of death, donors' age and steroid treatment. Results: Resistin levels were higher in DBDs both at BD diagnosis and before organ procurement compared to LD (p < 0.001). DBDs had significantly increased IL-1beta, IL-6, IL-8, IL-10 and TNF levels at both time points compared with LD. In DBDs, resistin at BD diagnosis correlated positively with IL-1beta (rs 0.468, p = 0.007), IL-6 (rs 0.511, p = 0.002), IL-10 (rs 0.372, p = 0.028), IL-12 (rs 0.398, p = 0.024), IL-13 (rs 0.397, p = 0.030) and TNF (rs 0.427, p = 0.011) at procurement. The cause of death, age over 60 and steroid treatment during BD did not affect resistin levels. However, steroid treatment significantly decreased pro-inflammatory cytokines IL-1beta, IL-8, TNF and IFN-gamma at the time of organ procurement. Conclusions: Resistin is increased early in DBDs, remains increased throughout the period of BD and correlates strongly with pro-inflammatory mediators. Resistin level, in contrast to cytokines, is not affected by steroid treatment. Resistin increase is related to the BD but is not influenced by age or cause of death. Resistin may be one of the initial triggers for the systemic inflammatory activation seen in DBDs. [ABSTRACT FROM AUTHOR]

Introduction: Resistin increases during several inflammatory diseases and after intracerebral bleeding or head trauma. Resistin activates the endothelium and may initiate an inflammatory response. No data are available on resistin in brain dead donors (DBD) that regularly manifest a pronounced inflammatory state. Methods: We analyzed plasma resistin in 63 DBDs and correlated results with donor variables and the postoperative course following kidney transplantation using organs from these donors. Endocan and monocyte chemotactic protein (MCP)-1 were also studied. Twenty-six live kidney donors (LD) and the corresponding kidney transplantations were used as controls. Results: DBDs had higher resistin (median/range 30.75 ng/ml, 5.41-173.6) than LD (7.71 ng/ml, 2.41-15.74, p < 0.0001). Resistin in DBD correlated with delayed graft function (DGF) in the kidney recipients (r = 0.321, p < 0.01); receiver operating characteristic curve revealed an area under the curve of 0.765 (95% confidence interval [CI] 0.648-0.881, p < 0.01) and a cut-off value for resistin of 25 ng/ml; MCP-1 and endocan were higher in DBDs (p < 0.0001) but did not correlate with DGF or acute rejection. No relationship was found between the studied molecules and the postoperative course of LD kidney transplants. Conclusions: High resistin levels in the DBD before organ retrieval are associated with DGF after kidney transplantation. The resistin increase seems related to the inflammatory state after brain death but not to the cause of death. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Advanced preservation injury (PI) after intestinal transplantation has deleterious short- and long-term effects and constitutes a major research topic. Logistics and costs favor rodent studies, whereas clinical translation mandates studies in larger animals or using human material. Despite diverging reports, no direct comparison between the development of intestinal PI in rats, pigs, and humans is available. We compared the development of PI in rat, porcine, and human intestines. Intestinal procurement and cold storage (CS) using histidine–tryptophan–ketoglutarate solution was performed in rats, pigs, and humans. Tissue samples were obtained after 8, 14, and 24 h of CS), and PI was assessed morphologically and at the molecular level (cleaved caspase-3, zonula occludens, claudin-3 and 4, tricellulin, occludin, cytokeratin-8) using immunohistochemistry and Western blot. Intestinal PI developed slower in pigs compared to rats and humans. Tissue injury and apoptosis were significantly higher in rats. Tight junction proteins showed quantitative and qualitative changes differing between species. Significant interspecies differences exist between rats, pigs, and humans regarding intestinal PI progression at tissue and molecular levels. These differences should be taken into account both with regards to study design and the interpretation of findings when relating them to the clinical setting. [ABSTRACT FROM AUTHOR]

Introduction: Uterus transplantation has recently proved that infertility in women with uterine factor infertility can be cured. It is still an experimental procedure with numerous critical details remaining to be established, including tolerance to warm and cold ischemic insults. In preparation for human uterus transplantation trials, most teams use the sheep as a model system for research and team training, since the vasculature and the uterus is of similar size as in the human. We, therefore, aimed to develop an ex vivo sheep uterus reperfusion platform that mimics the reperfusion situation so that initial assessments and comparisons can be performed without the need for costly and labor-intensive in vivo transplantation experiments.Material and Methods: Isolated sheep uteri were perfused with the preservation solution IGL-1 and were then exposed to cold ischemia for either 4 (n = 6) or 48 hours (n = 7). Uteri were then reperfused for 48 hours under normothermic conditions with an oxygenated recirculating perfusate containing growth factors and synthetic oxygen carriers. Histological and biochemical analysis of the perfusate was conducted to assess reperfusion injury.Results: Quantification of cell density indicated no significant edema in the myometrium or in the endometrium of uteri exposed to 4 hours cold ischemia and then a normothermic ex vivo reperfusion for 48 hours. Only the outer serosa layer and the inner columnar luminal epithelial cells were affected by the reperfusion. However, a much faster and severe reperfusion damage of all uterine layers were evident during the reperfusion experiment following 48 hours of cold ischemia. This was indicated by major accumulation of extracellular fluid, presence of apoptotic-labeled glandular epithelial layer and vascular endothelium. A significant accumulation of lactate was measured in the perfusate with a subsequent decrease in pH.Conclusions: We developed a novel ex vivo sheep uterus model for prolonged perfusion. This model proved to be able to distinguish reperfusion injury-related differences associated to organ preservation. The experimental setup is a platform that can be used to conduct further studies on uterine ischemia- and reperfusion injury that may lead to improved human uterus transplantation protocols. [ABSTRACT FROM AUTHOR]

Introduction: Resistin increases during several inflammatory diseases and after intracerebral bleeding or head trauma. Resistin activates the endothelium and may initiate an inflammatory response. No data are available on resistin in brain dead donors (DBD) that regularly manifest a pronounced inflammatory state.Methods: We analyzed plasma resistin in 63 DBDs and correlated results with donor variables and the postoperative course following kidney transplantation using organs from these donors. Endocan and monocyte chemotactic protein (MCP)-1 were also studied. Twenty-six live kidney donors (LD) and the corresponding kidney transplantations were used as controls.Results: DBDs had higher resistin (median/range 30.75 ng/ml, 5.41-173.6) than LD (7.71 ng/ml, 2.41-15.74, p < 0.0001). Resistin in DBD correlated with delayed graft function (DGF) in the kidney recipients (r = 0.321, p < 0.01); receiver operating characteristic curve revealed an area under the curve of 0.765 (95% confidence interval [CI] 0.648-0.881, p < 0.01) and a cut-off value for resistin of 25 ng/ml; MCP-1 and endocan were higher in DBDs (p < 0.0001) but did not correlate with DGF or acute rejection. No relationship was found between the studied molecules and the postoperative course of LD kidney transplants.Conclusions: High resistin levels in the DBD before organ retrieval are associated with DGF after kidney transplantation. The resistin increase seems related to the inflammatory state after brain death but not to the cause of death. [ABSTRACT FROM AUTHOR]