Differentiation between Wegener's granulomatosis and microscopic polyangiitis by an artificial neural network and by traditional methods.

Objective: To investigate the operating characteristics of the American College of Rheumatology (ACR) traditional format criteria for Wegener's granulomatosis (WG), the Sørensen criteria for WG and microscopic polyangiitis (MPA), and the Chapel Hill nomenclature for WG and MPA. Further, to develop and validate improved criteria for distinguishing WG from MPA by an artificial neural network (ANN) and by traditional approaches [classification tree (CT), logistic regression (LR)].

Methods: All criteria were applied to 240 patients with WG and 78 patients with MPA recruited by a multicenter study.

N-glycosylation of carnosinase influences protein secretion and enzyme activity: implications for hyperglycemia.

Objective: The (CTG)(n) polymorphism in the serum carnosinase (CN-1) gene affects CN-1 secretion. Since CN-1 is heavily glycosylated and glycosylation might influence protein secretion as well, we tested the role of N-glycosylation for CN-1 secretion and enzyme activity. We also tested whether CN-1 secretion is changed under hyperglycemic conditions.

Hypothermic injury: the mitochondrial calcium, ATP and ROS love-hate triangle out of balance.

Background/aims: Catecholamines prevent hypothermic cell death which accounts for severe tissue damage and impaired allograft function after prolonged organ preservation. Here, we identified cellular processes which govern hypothermia-mediated cell death in endothelial cells and how they are influenced by dopamine.

Methods: Lactate dehydrogenase assay, intracellular ATP, reactive oxygen species and reduced thio-group measurement, intracellular calcium measurement and mitochondrial calcium staining were performed in the study.

Atorvastatin donor pretreatment prevents ischemia/reperfusion injury in renal transplantation in rats: possible role for aldose-reductase inhibition.

Background: The aim of the present study was to evaluate the effect of donor pretreatment with atorvastatin on ischemia/reperfusion (I/R) injury in renal transplantation in rats.

Methods: Donor rats were pretreated orally with atorvastatin or vehicle 2 days prior to explantation. Kidneys were stored for 24 hr at 4 degrees C in University of Wisconsin solution and transplanted into isogeneic or allogeneic recipients.

Proteinuria-lowering effect of heparin therapy in diabetic nephropathy without affecting the renin-angiotensin-aldosterone system.

Angiotensin-converting enzyme inhibitors and angiotensin II (AngII) type 1 receptor blockers lower proteinuria and preserve renal function in diabetic nephropathy (DN). The antiproteinuric effects are greater than their blood pressure reduction, involving the sieving properties of the glomerular filter. In DN, glomerular staining for heparan sulfate proteoglycans is decreased.

L-carnosine, a substrate of carnosinase-1, influences glucose metabolism.

Objective: Carnosinase 1 (CN1) is a secreted dipeptidase that hydrolyzes L-carnosine. Recently, we have identified an allelic variant of human CN1 (hCN1) that results in increased enzyme activity and is associated with susceptibility for diabetic nephropathy in human diabetic patients. We therefore hypothesized that L-carnosine in the serum represents a critical protective factor in diabetic patients.

A CTG polymorphism in the CNDP1 gene determines the secretion of serum carnosinase in Cos-7 transfected cells.

Recently, we demonstrated that a polymorphism in exon 2 of the serum carnosinase (CNDP1) gene is associated with susceptibility to developing diabetic nephropathy. Based on the number of CTG repeats in the signal peptide, five different alleles coding for 4, 5, 6, 7, or 8 leucines (4L-8L) are known. Diabetic patients without nephropathy are homozygous for the 5L allele more frequently than those with nephropathy.

Dopamine treatment in brain-dead rats mediates anti-inflammatory effects: the role of hemodynamic stabilization and D-receptor stimulation.

Brain death (BD) is associated with profound inflammation in end-organs. Dopamine (DA) treatment reduces this inflammatory response, but the underlying mechanisms remain thus far largely unknown. In this study, we investigated if the anti-inflammatory effect of DA was related to hemodynamic stabilization and by which receptors it was mediated.

Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis.

Systemic vasculitis associated with autoantibodies to neutrophil cytoplasmic antigens (ANCA) is the most frequent cause of rapidly progressive glomerulonephritis. Renal failure at presentation carries an increased risk for ESRD and death despite immunosuppressive therapy. This study investigated whether the addition of plasma exchange was more effective than intravenous methylprednisolone in the achievement of renal recovery in those who presented with a serum creatinine >500 micromol/L (5.

Increased circulating endothelial progenitor cells in septic patients: correlation with survival.

Objective: Endothelial damage and detachment of endothelial cells are known to occur in septic patients. Thus, recruitment of circulating endothelial progenitor cells (cEPCs) to these lesions might have a beneficial effect on the clinical course in septic patients. Therefore, we were interested in whether EPCs, detected by flow cytometry, are increasingly mobilized during sepsis and if this mobilization is associated with clinical outcome.

Influence of hypersulfated and low molecular weight heparins on ischemia/reperfusion: injury and allograft rejection in rat kidneys.

The aim of the study was to evaluate the effect of the hypersulfated nonanticoagulant heparin derivative LU 51198 (LU) and of the low molecular weight heparin reviparin (REVI) on ischemia/reperfusion (I/R) injury, acute rejection (AR) and chronic allograft nephropathy (CAN) in rats. Organs were harvested 5 days after 60 min of renal I/R injury. For investigation of AR and CAN we used the allogeneic Fisher-Lewis model.

Donor dopamine pretreatment inhibits tubulitis in renal allografts subjected to prolonged cold preservation.

Background: In the present study, we used the Brown-Norway (BN) to Lewis model as a model for acute rejection, to test the hypothesis that dopamine (DA) treatment of BN donors significantly reduces the inflammatory response after renal transplantation.

Methods: BN and Lewis rats (isograft controls) were treated for 24 hr with DA (5 microg/kg/min) or NaCl (0.9%), respectively.

A leucine repeat in the carnosinase gene CNDP1 is associated with diabetic end-stage renal disease in European Americans.

Background: Four linkage analyses have identified a region on chromosome 18q22-23 that appears to harbour a diabetic nephropathy (DN) susceptibility locus. A trinucleotide repeat sequence in exon 2 of the carnosinase gene (CNDP1) residing on 18q22.3 was subsequently associated with DN in European Caucasians and Arabs.

Comparison of early renal function parameters for the prediction of 5-year graft survival after kidney transplantation.

Background: Early graft function (EGF) has an enduring effect on the subsequent course after kidney transplantation. This study compares quantitative parameters of EGF for the prediction of graft survival.

Methods: We involved 300 consecutive transplant recipients from deceased donors from 1989 to 2005.

Allelic variation in the CNDP1 gene and its lack of association with longevity and coronary heart disease.

Carnosine, a cytoprotective dipeptide found at very high concentrations in skeletal muscle, heart and brain, is cleaved in blood by serum carnosinase which is encoded by the CNDP1 gene. We recently found that homozygosity of a 5-leucine variant in the leader peptide of this enzyme protects diabetes mellitus patients against nephropathy. Hypothesising that the same allele could also be associated with longevity or a reduced incidence of cardiovascular problems, we examined the frequency of CNDP1 alleles in German centenarians, patients with premature coronary heart disease, and matched controls.

Hypothermia-induced loss of endothelial barrier function is restored after dopamine pretreatment: role of p42/p44 activation.

Background: Donor dopamine usage is associated with improved immediate graft function after renal transplantation. Although prolonged cold preservation results in an increased vascular permeability, the present study was conducted to examine in vitro and in vivo if dopamine pretreatment influences endothelial barrier function under such conditions.

Methods: To assess cold preservation injury in vitro and in vivo, cultured human umbilical vein endothelial cells (HUVEC) and Lewis donor rats were pretreated with dopamine or isotonic saline prior to cold storage.

Life-threatening intoxication with methylene bis(thiocyanate): clinical picture and pitfalls. A case report.

Background: Methylene bis(thiocyanate) (MBT) is a microbiocidal agent mainly used in industrial water cooling systems and paper mills as an inhibitor of algae, fungi, and bacteria.

Case Presentation: We describe the first case of severe intoxication following inhalation of powder in an industrial worker. Profound cyanosis and respiratory failure caused by severe methemoglobinemia developed within several minutes.

Tenilsetam prevents early diabetic retinopathy without correcting pericyte loss.

Hyperglycemia-induced mitochondrial overproduction of reactive oxygen species leads to the activation of different biochemical pathways involved in endothelial damage of the diabetic retina. Tenilsetam [(+/-)-3-(2-thienyl)-2-piperazinone] is a dicarbonyl scavenger in the millimolar range and a transition metal ion chelator in the micromolar range. We tested its effect on experimental diabetic retinopathy, and on endothelial cell characteristics in vitro.

Serial ANCA determinations for monitoring disease activity in patients with ANCA-associated vasculitis: systematic review.

Background: Antineutrophil cytoplasmic antibodies (ANCAs) are considered by some investigators to be sensitive markers of disease activity and have been suggested to predict relapse and guide therapeutic decisions. Studies using serial ANCA monitoring in patients with ANCA-associated vasculitis (AASV) have yielded controversial results during the last 15 years. To assess the diagnostic value of serial ANCA testing in the follow-up of patients with AASV, we conducted a systematic review of the available literature.

15-Deoxyspergualin and cyclophosphamide, but not mycophenolate mofetil, prolong survival and attenuate renal disease in a murine model of ANCA-associated crescentic nephritis.

Background: Here we compare the efficacy of cyclophosphamide (CYC) for treatment of crescentic nephritis (CGN) with the newer immunosuppressants 15-deoxyspergualin (DSG) and mycophenolate mofetil (MMF) in SCG/Kj mice, an inbred mouse strain that spontaneously develops CGN, systemic necrotizing vasculitis and antineutrophil cytoplasmic antibodies (ANCAs).

Methods: Mice were randomly assigned to intraperitoneal treatment with either DSG (2 mg/kg/day), CYC (50 mg/kg/week), MMF (60 or 100 mg/kg/day) or vehicle (VEH, dextrose 5% 0.3 ml/day) beginning at the 10th week of life.

Case-control study on analgesics and nephropathy (SAN): protocol.

Background: The association between intake of non-phenacetin-containing analgesics and the occurrence of chronic renal failure is still controversially discussed. A new epidemiologic study was planned and conducted in Germany and Austria.

Methods/design: The objective of the international, multicenter case-control study was to evaluate the association between end-stage renal disease (ESRD) and use of non-phenacetin-containing analgesics with particular emphasis on combined formulations.

Carnosine as a protective factor in diabetic nephropathy: association with a leucine repeat of the carnosinase gene CNDP1.

The risk of diabetic nephropathy is partially genetically determined. Diabetic nephropathy is linked to a gene locus on chromosome 18q22.3-q23.

Influence of donor pretreatment with dopamine on allogeneic kidney transplantation after prolonged cold storage in rats.

Background: Retrospective transplant database analysis revealed that administration of catecholamines to organ donors reduces acute rejection episodes and improves graft survival after renal transplantation. In the present study, the authors investigated the influence of dopamine donor pretreatment before prolonged cold storage on short- and long-term graft outcome after allogeneic kidney transplantation.

Methods: Fisher donor rats were treated intravenously for 24 hr with dopamine or isotonic saline, Lewis rats treated with saline served as controls.