Kynurenine serves as useful biomarker in acute, Long- and Post-COVID-19 diagnostics.

Introduction: In patients with SARS-CoV-2, innate immunity is playing a central role, depicted by hyperinflammation and longer lasting inflammatory response. Reliable inflammatory markers that cover both acute and long-lasting COVID-19 monitoring are still lacking. Thus, we investigated one specific inflammatory marker involved as one key player of the immune system, kynurenine (Kyn), and its use for diagnosis/detection of the Long-/Post-COVID syndrome in comparison to currently used markers in both serum and saliva samples.

Differences in Immune Response During Competition and Preparation Phase in Elite Rowers.

Metabolic stress is high during training and competition of Olympic rowers, but there is a lack of biomedical markers allowing to quantify training load on the molecular level. We aimed to identify such markers applying a complex approach involving inflammatory and immunologic variables. Eleven international elite male rowers (age 22.

Can wildland fire management alter 21st-century subalpine fire and forests in Grand Teton National Park, Wyoming, USA?

In subalpine forests of the western United States that historically experienced infrequent, high-severity fire, whether fire management can shape 21st-century fire regimes and forest dynamics to meet natural resource objectives is not known. Managed wildfire use (i.e.

Tryptophan-kynurenine profile in pediatric autoimmune hepatitis.

The impairment of regulatory T cells (Tregs) is a characteristic feature of autoimmune hepatitis (AIH), and the degradation of tryptophan (Trp) to kynurenine (Kyn), by gamma interferon-induced indoleamine-2,3-dioxygenase-1 (IDO-1), is a central metabolomics check point in the differentiation of Tregs. For this reason, we investigate whether or not Kyn and IDO activity is potentially useful biomarkers in pediatric AIH.Between January 2016 and January 2017, children of AIH type-1 (AIH-1, n = 37), AIH type-2 with liver kidney microsome-1 autoantibodies (AIH-2-LKM-1, n = 8), and autoantibody-negative Wilsons Disease (WD, n = 8) and alpha-1 anti-trypsin deficiency (AATD, n = 10), were enrolled in a cross-sectional survey of Kyn and Trp levels and Kyn/Trp ratios (IDO activity) by HPLC, and neopterin levels by ELISA.

Dynamics and Diagnostic Relevance of Kynurenine Serum Level after Kidney Transplantation.

Background: Inflammatory events after kidney transplantation (Tx) may lead to activation of the tryptophane-catabolizing enzyme indoleamine 2,3-dioxygenase followed by the formation of kynurenine (KYN). Post-transplant KYN serum levels in kidney allograft recipients were analyzed for their diagnostic value.

Material And Methods: This was a retrospective analysis of KYN levels (normal value: 2.

Anti-inflammatory and anti-proliferative effects of CBS3830 in arterialized vein grafts in rats.

Objective: To investigated whether CBS3830, a highly selectively inhibitor of p38MAPK, could ameliorate inflammation and intimal hyperplasia in arterialized vein grafts (AVGs).

Methods: Sixty male Sprague-Dawley rats underwent a reversed right jugular vein to common carotid artery interposition graft and were randomly treatment with vehicle (control) or single-dose (3 mg/kg, preoperative) or double-dose (3 mg/kg, preoperative and 4 d postoperative) CBS3830. Twenty rats underwent sham operation.

Causes and prognostic value of pre-transplant elevated kynurenine level in kidney allograft recipients.

Background: The activation of the tryptophane catabolizing enzyme Indoleamine 2,3-dioxygenase leads to the formation of kynurenine and other metabolites that counter-regulate immune activation resulting in restoration of immune homeostasis. But in chronic immune activation, as in hemodialysed patients, the immunosuppressive feedback mechanisms continue as indicated by elevated kynurenine concentrations. However, its relevance is still a matter of debate.

p38 MAPK inhibitor, CBS3830 limits vascular remodelling in arterialised vein grafts.

Objective: Following bypass surgery vein grafts undergo a remodelling process that can lead to restenosis and ultimately vein graft failure. Signalling through mitogen activated protein kinases (MAPKs) is a key mechanism involved in vein graft failure. Here, we investigated whether CBS3830 (c-a-i-r biosciences GmbH, Tübingen, Germany), a new highly selectively inhibitor of p38 MAPK, has a significant effect on inhibiting intimal, medial and adventitial hyperplasia.

Neither mycophenolate acyl-glucuronide levels nor their areas under the curve are responsible for the gastrointestinal side effects in kidney transplant recipients receiving EC-MPA: a prospective trial.

Introduction: Since previous in vitro studies suspected the metabolite mycophenolate acyl-glucuronide (AcMPAG) to be responsible for the gastrointestinal side effects, we examined the correlation between AcMPAG blood levels and patient gastrointestinal satisfaction inquiries using a standardized, validated questionnaire.

Patients And Methods: We enrolled 63 renal transplant patients, however, two discontinued the study and 16 were excluded because of inadequate completion of the questionnaires or missing blood values or discontinuation of enteric coated mycophenolic acid (EC-MPA) therapy, severe side effects or viral infections. The final responses of 45 people were subjects to statistical analysis.

Customized mycophenolate dosing based on measuring inosine-monophosphate dehydrogenase activity significantly improves patients' outcomes after renal transplantation.

Background: Significant relationships have been reported between the uptake of mycophenolic acid (MPA) and the risk of acute rejection. In a prospective study after renal transplantation, we assessed the value of measuring inosine-monophosphate dehydrogenase (IMPDH) activity as a predictive indicator of an acute rejection episode in the initial postoperative period.

Patients And Methods: Fifty-two patients received 360 mg enteric-coated mycophenolate-sodium two times per day with concomitant tacrolimus/cyclosporine A, providing a total of 122 pharmacodynamic profiles.

Relationship of hepatitis B or C virus prevalences, risk factors, and outcomes in renal transplant recipients: analysis of German data.

Background: Chronic liver disease resulting from hepatitis B (HBV) and hepatitis C (HCV) virus infections is still a major concern in kidney recipients. Our aim was to evaluate the prevalences, risk factors, and impact of HBV and HCV infections in adult renal transplant recipients in Germany.

Materials And Methods: Data were collected on 1633 kidney recipients transplanted between 1989 and 2002 at the 21 German renal transplant centers participating in MOST, the prospective Multinational Observational Study in Transplantation.

Renal ischemia/reperfusion and its influence on telomere length and expression of cell cycle regulatory genes.

The aim of the study was to evaluate the influence of renal ischemia/reperfusion (I/R) on telomere (T) length and tissue expression of cyclin-dependent kinase inhibitor genes (CDKIG). An experimental model of ex-vivo hemoperfusion of the kidney was used as described earlier. Telomere length measurement and expression of p16((INK4a)), p21((WAF1/CIP1)) and p27((Kip1)) CDKIGs was studied immunohistochemically in kidney biopsy samples at baseline and different time points after the reperfusion.

Severe graft rejection, increased immunosuppression, and active CMV infection in renal transplantation.

Associations between active cytomegalovirus (CMV) infection, graft rejection, rejection therapy, and clinical signs and symptoms have been shown repeatedly. However, the causes and the sequence of events remain an area of debate. Two hundred twenty five patients with cadaveric renal transplant were included in the present study.

Up-regulation of cell cycle regulatory genes after renal ischemia/reperfusion: differential expression of p16(INK4a), p21(WAF1/CIP1) and p27(Kip1) cyclin-dependent kinase inhibitor genes depending on reperfusion time.

The aim of this study was to evaluate the influence of renal ischemia, cold preservation and reperfusion on the degree of renal kidney senescence. An experimental model of ex vivo renal hemoperfusion was used. Expression of p16(INK4a), p21(WAF1/CIP1) and p27(Kip1) cyclin-dependent kinase inhibitor genes (CDKIGs) was studied immunohistochemically in kidney biopsy samples at baseline and different time points after reperfusion.

Cyclosporine C2 levels in de novo renal allograft recipients: a German multicenter prospective observational study.

This ongoing multicenter prospective observational study was undertaken in de novo renal allograft recipients managed with cyclosporine (CsA) trough (C0) and 2-hour postdose (C2) level monitoring at defined times so as to assess the risk for an acute rejection episode or allograft dysfunction. The renal transplant recipients (n = 159) were enrolled at 11 German centers. The 6-month posttransplant data from 138 patients were evaluable for this interim analysis.

Cyclosporine-based immunosuppressive strategies for kidney recipients: interim analysis of German data from the Multinational Observational Study (MOST).

Introduction: We collected data from kidney recipients with a functioning graft at German kidney transplant centers in order to analyze the efficacy of various cyclosporine (CsA)-based immunosuppressive strategies, the effects of different perioperative and maintenance regimens, and the impact of donor source on clinical outcome.

Methods: As part of the ongoing prospective Multinational Observational Study in Transplantation (MOST), data for both prospective and retrospective analysis were collected from kidney recipients over 18 years bearing a functioning graft that was transplanted at 21 German kidney transplant centers between 1987 and 2002.

Results: Data from 1223 renal graft recipients, including their CsA-based immunosuppressive regimens, were stratified as: 402 de novo patients (median 6.

Rapamycin rescue therapy in patients after kidney transplantation: first clinical experience.

This study was aimed at analysing rapamycin (RAPA) rescue therapy with calcineurin inhibitor (CNI) withdrawal in renal transplant patients primarily presenting with CNI-nephrotoxicity (CNI-Neph), chronic allograft nephropathy (CAN) without [CAN(a)] and with histological changes suggestive of chronic rejection [CAN(b)]. In 36 patient with CNI-Neph (n = 6), CAN(b) (n = 21), CAN(a) (n = 7), and others (n = 2) RAPA therapy was started 4.4-115 months (median 30.

Influence of ischaemia/reperfusion and LFA-1 inhibition on telomere lengths and CDKI genes in ex vivo haemoperfusion of primate kidneys.

The telomere (T) length, p21(WAF1/CIP1) and p27(Kip1) cyclin-dependent kinase inhibitor (CDKI) genes are the markers of cell senescence and DNA damage. The aim of the study was to determine the influence of renal ischaemia/reperfusion (I/R) and anti-lymphocyte function-associated antigen-1 (LFA-1) monoclonal antibody (mAb) treatment on the value of the above-mentioned markers. Significantly higher levels of p21 and p27 were expressed by the glomeruli (P=0.

Effect of ischemia/reperfusion on telomere length and CDKI genes expression in a concordant ex-vivo hemoperfusion model of primate kidneys.

Objectives: The telomere (T) length, p21(WAF1/CIP1) and p27(Kip1) cyclin dependent kinase inhibitor (CDKI) genes are considered the markers of cell senescence and DNA damage. The aim of the study was to evaluate the influence of renal ischemia/reperfusion (I/R) on the value of above-mentioned markers.

Methods: 13 Macaque cynomolgus monkey kidneys were harvested and placed in Eurocollins solution.

Experience with therapeutic drug monitoring of cyclosporine.

During the past 20 years, cyclosporine (CsA) has become the main part of immunosuppressive protocols. Its impact to improve the quality and quantity of transplantation surgery has been enormous. Immunosuppression in allograft recipients 10 years after renal transplantation CsA continued to demonstrate benefits on graft survival without evidence of long-term morbidity.

[Prevention of ischemia before cold ischemia by pharmcologic donor conditioning--experimental findings].

The loop-diuretic piretanide was used to study the influence of pharmacological donor pretreatment on immediate postischemic function in a pig model of kidney transplantation based on the results of a clinical pilot study [4]. Following laparotomy, both kidneys were flushed via a transaortal catheter with Eurocollins-solution and surgically removed. A cold ischemic period of 1 or 24 h was chosen.

Ex-vivo hemoperfusion (eHPS) of pig-lungs with whole human blood: effects of complement inhibition with a soluble C1-esterase-inhibitor.

Objectives: Xenotransplantation could be a future alternative to allotransplantation due to increasing organ shortage. Complement activation plays a major role in hyperacute rejection (HAR) in pig-to-human combinations. We developed an ex-vivo hemoperfusion (EHP) system to investigate pathophysiology of HAR in the lung.

Urinary endotoxin excretion and urinary tract infection following kidney transplantation.

Following kidney transplantation, urine endotoxin levels were measured among 44 patients and compared to bacterial cultures. Urine samples were collected either via transurethral catheters or - after removal of the catheter on postoperative day 4 - by midstream void. In a control group of ten healthy volunteers, urine endotoxin levels were measured daily for 10 days.

Possible oxcarbazepine interaction with cyclosporine serum levels: a single case study.

We studied the influence of an add-on medication with oxcarbazepine on the cyclosporine trough level in a kidney transplant recipient with pharmacoresistant epilepsy. Two weeks after the beginning of the trial we observed a decrease of the cyclosporine trough and the Na serum levels. Both could be corrected by a small-dose reduction of oxcarbazepine, an augmentation of the cyclosporine dosis, and oral sodium chloride substitution.