BACKGROUND:N-acetylcysteine (NAC) has been proposed to prevent radiocontrast nephropathy in high-risk patients.METHODS:The effect of single-dose and prolonged administration of NAC before application of either the ionic, high-osmolar radiocontrast agent diatrizoate sodium (DTZ) or the nonionic, low-osmolar radiocontrast agent iohexol (IOH) in a rat model combining uninephrectomy, salt depletion, and administration of indomethacin was explored. Arterial blood pressure and total, cortical, and medullary blood flow were continuously recorded in anesthetized Sprague-Dawley rats.RESULTS:NAC had no effect on renal hemodynamics in control rats. Both DTZ and IOH induced biphasic changes in renal blood flow and cortical renal blood flux and persistently reduced medullary blood flux. Neither single-dose nor prolonged administration of NAC prevented the hemodynamic changes following administration of DTZ or IOH, respectively. Acute prophylactic administration of NAC prevented increased urinary ET excretion after injection of IOH and, to a smaller degree, of DTZ. Both an ionic, high-osmolar (DTZ) and a nonionic, low-osmolar (IOH) radiocontrast agent induce marked changes in renal hemodynamics in salt-depleted rats treated with indomethacin.CONCLUSIONS:Renal perfusion is not affected by NAC application in a model of experimental contrast nephropathy in rats. Other effects of NAC might thus account for the presumed renoprotective properties.

Introduction: The pathogenesis of calcium oxalate stone formation is not completely understood. Recently, an influence of vascular phenomena like arteriosclerosis on the crystallization process was hypothesized. Thus, stone formation should be more common in patients with diabetes mellitus (DM) who are at risk of developing angiopathy. The aim of the study was to determine the prevalence of urolithiasis (UL) in patients with DM and to identify specific risk factors. Material and Methods: 350 patients with DM were evaluated with respect to DM-related history, and a total of 179 patients was included (83 female, 96 male; age 23–84 years). All patients were interviewed to assess the history of stone formation. These data were compared to epidemiological data in Germany. Results: The overall prevalence of UL in the diabetic group was 7.82% (vs. 4.73% in Germany, p = 0.0485; binominal test). The prevalence was significantly higher in patients with coronary heart disease (25%; p < 0.0001; Fisher‘s exact test). We could not demonstrate an increased prevalence of UL for patients with occlusive arterial disease or arterial hypertension as diabetic nephropathy was not a risk factor for developing urinary lithiasis (p = 0.7184, p = 1.000, p = 0.6266, respectively; Fisher’s exact test). Thiazide medication lowered the prevalence of stone formation (p = 0.0399; Fisher’s test). Calcium or magnesium supplementation did not influence stone formation significantly (p = 0.5279; p = 1.000; respectively; Fisher’s test). Conclusions: In Germany, patients with DM are at higher risk of UL compared with patients without diabetes. We demonstrated a significantly higher prevalence of urinary stones in patients with coronary heart disease. These findings are consistent with the hypothesis that urinary stone formation has a vascular pathogenesis in part.

A 33-year-old woman from Laos was admitted due to recurrent vomiting and weight loss. Since one year, she was receiving immunosuppressive therapy (azathioprine 50 mg/d and methylprednisolone 18 mg/d) for a mixed connective tissue disease. Because of a drug induced Stevens-Johnson-Syndrome one month earlier high doses of methylprednisolone (100 mg/d intravenously) had been administered. The patient's general condition was reduced. Examination elicited a mild pain in the middle abdomen on palpation but no resistance or tumour. The differential diagnosis included obstructive and (or) inflammatory disease of the gastrointestinal tract.Elevated IgE-levels (1111 IU/ml; normal up to 100 IU/ml) and eosinophilia (8%) lead to the suspicion of a helminthiasis. Oesophagogastroduodenoscopy showed a significant duodenal stenosis. Duodenal biopsy revealed a severe infestation with Strongyloides stercoralis. Stool examinations were negative though.With administration of thiabendazole (2 g/d) a rapid recovery was noted. A second oesophagogastroduodenoscopy one week after the onset of therapy revealed no further stenosis. Since there was no activity of the mixed connective tissue disease the methylprednisolone dosage was reduced and the administration of azathioprine was ceased. 3 weeks after beginning of treatment the patient was discharged in improved condition.In immunocompromised patients suffering from gastrointestinal complaints who have been in endemic areas an infection with Strongyloides stercoralis should be excluded. Without treatment, this helminthiasis may be fatal.

Brain death (BD) is associated with tissue inflammation. As dopamine treatment of BD donor rats reduces renal monocyte infiltration, we tested if this treatment affects renal function and inflammation in recipients. BD was induced in F344 rats and was maintained for 6 h in all experiments. Dopamine was given for 6 (DA6) or 3 h (DA3) from the onset of BD. Ventilated non-BD (NBD) and BD animals served as controls. Kidneys were transplanted into bilaterally nephrectomized Lewis recipients. Serum creatinine (s-crea) was measured and leukocyte infiltration was assessed 10 days after transplantation. One day after transplantation, s-crea was significantly reduced in recipients who received a renal allograft from dopamine treated BD or from NBD rats compared to BD vehicle (P < 0.05). Ten days after transplantation, the number of infiltrating monocytes was significantly lower in grafts obtained from dopamine treated and from NBD rats (P < 0.05). A reduced infiltration in these grafts was confirmed by Banff 97 classification. Cytokine-induced neutrophil-chemoattractant 1 and interleukin (IL)-6 mRNA expression were reduced in DA rats compared to BD controls. No difference for macrophage chemoattractant protein 1 and IL-10 were found. These findings may explain the salutary effect of donor dopamine treatment in renal transplantation.

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°C in University of Wisconsin solution and transplanted into isogeneic or allogeneic recipients. Results. Donor treatment with atorvastatin improved initial graft function, reduced renal inflammation, and the number of TUNEL-positive cells in renal tissue after prolonged cold storage and isogeneic transplantation. In the allogeneic transplantation model, donor treatment with atorvastatin reduced renal inflammation in grafts harvested after 5 days, but no improvement of long-term graft survival (24 weeks) could be observed. A genome wide gene expression profile of donor kidneys from atorvastatin treated or vehicle treated rats revealed a fivefold downregulation of aldose reductase in all atorvastatin treated animals (P<0.01). Donor treatment with an aldose-reductase inhibitor improved kidney function and reduced renal inflammation after prolonged cold storage and isogeneic transplantation. Conclusion. Our data suggest that downregulation of aldose reductase in renal tissue might underlie the protective effect of donor atorvastatin treatment. Donor pretreatment with a statin or an aldose reductase inhibitor could offer a new treatment strategy to prevent transplantation associated tissue injury.

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. Kidneys were harvested at one respectively 32 weeks after transplantation. Rats were treated with either vehicle, LU or REVI. After I/R injury, treatment with REVI or LU reduced infiltration with MHC II and R73-positive cells, whereas only REVI reduced ED1-positive cells and expression of monocyte chemoattractant protein-1. There was no effect of REVI and LU on acute allograft rejection. Treatment with LU or REVI reduced glomerular infiltration with ED1 and MHCII-positive cells and renal expression of transforming growth factor-beta 32 weeks after transplantation. Only REVI treatment reduced albuminuria, interstitial infiltration and histological signs of CAN. LU, and in a more potent manner REVI, reduce signs of CAN and renal inflammation after I/R injury. Chemically modified heparins without anticoagulatory effects may offer a new treatment option in preventing I/R injury and CAN in human kidney transplantation.

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. BD was induced in F344 donor rats. DA was given either before BD for 24 h or after BD induction during a definite time. Adrenergic or D-receptor blockers were administered to inhibit the receptor stimulation mediated by DA. Hemodynamic changes were recorded and kidneys were harvested after 6 h of BD. Mean arterial pressure was completely normalized by DA treatment. DA pretreatment before BD induction and treatment during BD both significantly inhibited the monocyte infiltration. The anti-inflammatory as well as its blood pressure stabilizing effect was abrogated by concomitant application of adrenergic receptor blockers. In contrast, concomitant application of D-receptor blockers only abrogated the anti-inflammatory effect, but did not affect blood pressure stabilization. In contrast, pergolide and adrenergic receptor blockers completely normalized the blood pressure, but did not affect renal inflammation. Hence, DA might reduce BD-induced monocyte infiltration possibly by hemodynamic stabilization, D-receptor activation, or a combination of both.

Background and Purpose: To assess the appearance of carotid artery stents at 3.0Tesla contrast enhanced magnetic resonance angiography (CE-MRA) as compared with 1.5Tesla. Methods: 19 stents (GUIDANT Acculink, GUIDANT Dynalink, BOSTON SCIENTIFIC SMART Neuroform, GUIDANT Omnilink, EV3 Protege, BOSTON SCIENTIFIC Carotid Wallstent, ABBOTT Xact) of different materials (nitinol, stainless steal, cobalt alloy) and different sizes (4.0mm-10.0mm) were investigated regarding their appearance on CE-MRA at 3.0Tesla and at 1.5 Tesla. For each stent artificial lumen narrowing (ALN) was calculated based on a pixel-bypixel profile of the contrast-to-noise-ratio giving an objective indicator for the size of the evaluable stent diameter. Results: Only in two stents (Omnilink 7.0mm, Omnilink 10.0mm) was ALN higher at 3.0Tesla relative to 1.5Tesla. In all other stents ALN at 3.0Tesla was the same or even lower as compared with 1.5Tesla. In contrast to the ferromagnetic stents where ALN was typically higher than 85%, in most of the nitinol stents (Acculink, Dynalink, Neuroform, Protege) ALN was below 35%. In the Xact stents ALN was generally 100% at 1.5Tesla and ranged between 31.8% and 100% at 3.0Tesla. Conclusion: CE-MRA after carotid artery stenting is considerably impaired by ALN both at 1.5Tesla and at 3.0Tesla. Nevertheless, CE-MRA is well suited for the examination of carotid artery stents made of nitinol at both field strengths. Stent manufacturers should be aware of potential artifacts caused by their stents during noninvasive diagnostic methods such as CE-MRA.

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. Despite immediate admission to the intensive care unit, where mechanical ventilation and hemodialysis for toxin elimination were initiated, multi-organ failure involving liver, kidneys, and lungs developed. While liver failure was leading, the patient was successfully treated with the MARS (molecular adsorbent recirculating system) procedure. Conclusion Intoxication with MBT is a potentially life-threatening intoxication causing severe methemoglobinemia and multi-organ failure. Extracorporeal liver albumin dialysis (MARS) appears to be an effective treatment to allow recovery of hepatic function.

Background and Purpose: To assess the appearance of carotid artery stents at 3.0Tesla contrast enhanced magnetic resonance angiography (CE-MRA) as compared with 1.5Tesla.Methods: 19 stents (GUIDANT Acculink, GUIDANT Dynalink, BOSTON SCIENTIFIC SMART Neuroform, GUIDANT Omnilink, EV3 Protege, BOSTON SCIENTIFIC Carotid Wallstent, ABBOTT Xact) of different materials (nitinot, stainless steal, cobalt alloy) and different sizes (4.0mm-10.0mm) were investigated regarding their appearance on CE-MRA at 3.0Tesla and at 1.5 Tesla. For each stent artificial lumen narrowing (ALN) was calculated based on a pixel-by-pixel profile of the contrast-to-noise-ratio giving an objective indicator for the size of the evaluable stent diameter.Results: Only in two stents (Omnilink 7.0mm, Omnilink 10.0mm) was ALN higher at 3.0Tesla relative to 1.5Tesla. In all other stents ALN at 3.0Tesla was the same or even lower as compared with 1.5Tesla. In contrast to the ferromagnetic stents where ALN was typically higher than 85%, in most of the nitinol stents (Acculink, Dynalink, Neuroform, Protege) ALN was below 35%. In the Xact stents ALN was generally 100% at 1.5Tesla and ranged between 31.8% and 100% at 3.0Tesla.Conclusion: CE-MRA after carotid artery stenting is considerably impaired by ALN both at 1.5Tesla and at 3.0Tesla. Nevertheless, CE-MRA is well suited for the examination of carotid artery stents made of nitinol at both field strengths. Stent manufacturers should be aware of potential artifacts caused by their stents during noninvasive diagnostic methods such as CE-MRA.

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. ANCA, blood urea nitrogen (BUN) and proteinuria were determined in all animals regularly, and survival was calculated. Renal histology was obtained in the 18th week of life in the MMF- or VEH-treated groups and in the 24th week in DSG- or CYC-treated animals.Results. Mean survival in VEH-treated animals was 123 days. At that point, survival was 100% in the CYC- or DSG-treated animals (P < 0.001). Survival in the MMF group (pooled data) was not significantly different from the VEH-treated animals [MMF, 117 days (95% CI 108-127)]. BUN (18th week, CYC 43 +/- 9 mg/dl and DSG 36 +/- 6 mg/dl vs VEH 73 +/- 28 mg/dl, P < 0.001, MMF 66 +/- 26 mg/dl), 24 h proteinuria (18th week, CYC 0.4 +/- 0.2 mg and DSG 0.7 +/- 0.6 mg vs VEH 2.7 +/- 3 mg, P < 0.001, MMF 2.2 +/- 3 mg) crescent formation (18th week, VEH 42 +/- 9%, MMF 39 +/- 11%; CYC 5 +/- 2% and DSG 22 +/- 7% vs VEH, P < 0.05), glomerular immune complex deposition, and ANCA formation were significantly improved in CYC- and DSG- but not in MMF-treated animals when compared with controls.Conclusion. DSG and CYC, but not MMF, prolong life, limit renal damage and prevent autoantibody formation in SCG/Kj mice.

Treatment of organ donors with catecholamines reduces acute rejection episodes and improves long-term graft survival after renal transplantation. The aim of this study was to investigate the effect of catecholamine pre-treatment on ischemia/reperfusion (I/R)-and cold preservation injury in rat kidneys. I/R-injury was induced by clamping the left kidney vessels for 60 min along with a contralateral nephrectomy. Cold preservation injury was induced by storage of the kidneys for 24 h at +/- 4 degrees C in University of Wisconsin solution, followed by syngeneic transplantation. Rats were pre-treated with either dopamine (DA), dobutamine (DB), or norepinephrine ( 2, 5, and 10 mu g/kg/min, each group) intravenously via an osmotic minipump for 24 h before I/R- and cold preservation injury. Pre-treatment with DA (2 or 5 mu g/kg/min) and DB ( 5 mu g/kg/min) improved recovery of renal function after I/R- injury and dose dependently reduced mononuclear and major histocompatibility complex class II-positive cells infiltrating the kidney after I/R- injury. One day after I/R-injury, upregulation of transforming growth factor (TGF)-beta 1 and 2 and phosphorylation of p42/p44 mitogen-activated protein kinases was observed in kidneys of animals treated with DA or DB. DA ( 5 mu g/kg/min) and DB ( 5 mu g/kg/min) pre-treatment reduced endothelial cell damage after 24 h of cold preservation. Only DA pre-treatment improved renal function and reduced renal inflammation after 24 h of cold preservation and syngeneic transplantation. Our results demonstrate a protective effect of pre-treatment with catecholamines on renal inflammation and function after I/R- or cold preservation injury. This could help to explain the potent organoprotective effects of catecholamine pre-treatment observed in human kidney transplantation.

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. Injury was determined by lactate dehydrogenase (LDH) release, histology, and functional analysis.RESULTS:In vitro cold storage resulted in intercellular gap formation in both untreated and dopamine pretreated HUVEC. In the latter monolayer integrity was completely restored upon rewarming and paracellular transport of fluorescein isothiocyanate-dextran was significantly reduced. In dopamine treated HUVEC, intercellular gap formation was independent of cell death and was associated with redistribution of junctional proteins and condensation of cytoskeleton proteins. In untreated HUVEC proteolysis and cell death were clearly evident after hypothermia. Closing of intercellular gaps was dependent on p42/p44 activation. Regeneration of adenosine triphosphate was only observed in dopamine pretreated cells. Only in dopamine treated Lewis renal allografts subjected to cold storage, activation of p42/p44 occurred upon rewarming. These grafts had a better renal function and displayed less inflammatory cells five days after transplantation.CONCLUSION:Our study demonstrates beneficial effects of dopamine treatment on cold storage induced endothelial barrier disturbances. This may contribute to the positive effects of catecholamines on immediate graft function of renal allografts in men.

Although a beneficial effect of hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, i.e. statins, on cell-mediated immunity has been suggested in vivo and in vitro, little is known about the molecular and biochemical events by which statins inhibit T cell proliferation. To address this question, we investigated the effects of atorvastatin (AT) on intracellular cytokine production, T cell activation markers, cell cycle progression and apoptosis in human CD4(+) T cells. AT did not influence intracellular cytokine production after short-term stimulation of whole blood with phorbol myristate acetate (PMA)/ionomycin or superantigen (SEB). In contrast, AT influenced CD45RA to RO switching dose-dependently, as well as CD25 expression, and caused cell cycle arrest in the G1 phase after long-term T cell stimulation. This occurred in conjunction with a reduced expression of cyclin-dependent kinases 2 and 4 and p21(wav1/cip1) and was paralleled by an increased protein expression of p27(kip1). In addition to G1 arrest, increased apoptosis was observed in AT-treated cells. In line with this, the expression of Bcl-xl and pBad were decreased by AT. Apoptosis was independent of caspases 3 and 9 activation. The inhibitory effect of AT on T cell proliferation could be overcome by addition of mevalonic acid or geranylgeranyl pyrophosphate, but not by farnesyl pyrophosphate or squalen, suggesting reduced protein prenylation. Activation of Rho, Rac and Ras were strongly reduced in AT-treated T cells, suggesting that impaired geranylation of these molecules might underlie the inhibitory effect of AT on T cell proliferation.

Background and Purpose: To assess the appearance of carotid artery stents at 3.0Tesla contrast enhanced magnetic resonance angiography (CE-MRA) as compared with 1.5Tesla. Methods: 19 stents (GUIDANT Acculink, GUIDANT Dynalink, BOSTON SCIENTIFIC SMART Neuroform, GUIDANT Omnilink, EV3 Protege, BOSTON SCIENTIFIC Carotid Wallstent, ABBOTT Xact) of different materials (nitinol, stainless steal, cobalt alloy) and different sizes (4.0mm-10.0mm) were investigated regarding their appearance on CE-MRA at 3.0Tesla and at 1.5 Tesla. For each stent artificial lumen narrowing (ALN) was calculated based on a pixel-bypixel profile of the contrast-to-noise-ratio giving an objective indicator for the size of the evaluable stent diameter. Results: Only in two stents (Omnilink 7.0mm, Omnilink 10.0mm) was ALN higher at 3.0Tesla relative to 1.5Tesla. In all other stents ALN at 3.0Tesla was the same or even lower as compared with 1.5Tesla. In contrast to the ferromagnetic stents where ALN was typically higher than 85%, in most of the nitinol stents (Acculink, Dynalink, Neuroform, Protege) ALN was below 35%. In the Xact stents ALN was generally 100% at 1.5Tesla and ranged between 31.8% and 100% at 3.0Tesla. Conclusion: CE-MRA after carotid artery stenting is considerably impaired by ALN both at 1.5Tesla and at 3.0Tesla. Nevertheless, CE-MRA is well suited for the examination of carotid artery stents made of nitinol at both field strengths. Stent manufacturers should be aware of potential artifacts caused by their stents during noninvasive diagnostic methods such as CE-MRA.