bluuebunny/crossref_metadata_2025 huggingface dataset:
Transforming Growth Factor-β1 May Be Involved in Shunt Obstruction in Patients on Chronic Hemodialysis
Authors: Taniguchi Yoshihiko , Yorioka Noriaki , Yamashita Kazuomi , Masaki Takao , Yamakido Michio
Published: April 2003

Obstructed shunt vessels were studied immunohistochemically to clarify the mechanism of shunt obstruction in hemodialysis patients. The subjects were 12 hemodialysis patients with shunt obstruction, and 8 patients newly started on hemodialysis were used as the controls. Cryosections of shunt tissue were prepared and stained for thrombomodulin as well as transforming growth factor-β1 using the enzyme antibody method. In the obstructed shunt group, the intima was significantly thicker than in the control group. In addition, staining of the intima for thrombomodulin was decreased in the obstructed shunt group when compared with the controls. Staining for transforming growth factor-β1 was related to intimal thickening and cell proliferation. These results indicate that release of thrombomodulin occurs with vascular endothelial cell damage and that transforming growth factor-β1 may be involved in intimal hypertrophic change and shunt obstruction.
Complement Activation Accelerates Glomerular Injury in Diabetic Rats
Authors: Fujita T. , Ohi H. , Komatsu K. , Endo M. , Ohsawa I. , Kanmatsuse K.
Published: April 2003

A known inhibitor of the complement cascade (K-76 COONa) was administered to an inbred diabetic rat model to investigate whether the complement system may play a role in the progression of diabetic glomerulosclerosis. Drinking water containing K-76 COONa was available continuously to inbred diabetic rats (Otsuka Long-Evans Tokushima Fatty, OLETF) from the age of 25 to 55 weeks (Group L). Drinking water without K-76 COONa was similarly available to OLETF rats (Group H) and nondiabetic control rats (Long-Evans Tokushima Otsuka, LETO) (Group C). The levels of plasma glucose (mg/dl) at the 55th week were 156 ± 16 in Group C, 252 ± 18 in Group L and 349 ± 93 in Group H. There was no significant difference in the degree of diabetes between Group L and Group H. The levels of urinary protein at 55 weeks of age (mg/day) were 2.1 ± 0.4 in Group C, 11.6 ± 1.5 in Group L and 18.0 ± 2.8 in Group H. The level of urinary protein was significantly decreased by the administration of K-76 COONa. Histological examination of renal specimens from the sacrificed rats at 55 weeks of age revealed diffuse mesangial expansion in almost all glomeruli in Group H, exudative lesions in 30% of glomeruli in Group H, and only mild mesangial expansion was recognized in Group L. Immunofluorescence study revealed brilliant staining of C3 and immunoglobulins (Ig) in Group H; trace staining of Ig and no staining of C3 were recognized in Group L. The incubation study with guinea pig serum and glomeruli from rats revealed that Ig and complement components also bound to injured glomeruli in vitro. These data indicate that the complement cascade is activated by injured glomeruli and this activation exacerbates diabetic glomerulosclerosis.
Lipid Profiles in Patients with Atherosclerotic Renal Artery Stenosis
Authors: Scoble J.E. , de Takats D. , Ostermann M.E. , Connolly J.O. , Scott N.R. , Beeso J.A. , Poyser K.H. , Peters T.J. , Sherwood R.A.
Published: April 2003

Background: Atherosclerotic renal artery stenosis (ARAS) is an important cause of renal disease in the elderly, and these patients have a high morbidity and mortality. There are no data on their blood lipid profiles. Methods: The lipoprotein profiles were examined in patients with proven ARAS and compared with patients matched for age, gender, renal function and presence of diabetes. Results: The profiles did not show any significant difference for apolipoprotein B (control 1.31 ± 0.39 vs. ARAS 1.24 ± 0.28; mean ± SD), cholesterol (control 5.65 ± 1.28 vs. ARAS 6.12 ± 1.29), LDL cholesterol (control 3.72 ± 1.03 vs. ARAS 4.06 ± 1.18), fibrinogen (control 2.48 ± 1.39 vs. ARAS 3.29 ± 1.49), HDL cholesterol (control 1.16 ± 0.38 vs. ARAS 1.00 ± 0.26) and triglyceride (control 1.68 ± 0.80 vs. ARAS 2.32 ± 1.73) levels between the groups. Surprisingly lipoprotein(a) levels were higher in the control group (0.58 ± 0.45) vs. ARAS (0.31 ± 0.21). The most striking abnormality was the markedly lower apolipoprotein A1 levels in the ARAS group (control 2.09 ± 0.55 vs. ARAS 0.95 ± 0.30) and apolipoprotein A1/B ratio (control 1.74 ± 0.71 vs. ARAS 0.78 ± 0.24). Conclusion: The lipoprotein abnormality in ARAS mirrors that in other severe vascular diseases. Potential therapeutic interventions in patients with ARAS should consider treatments to modify the apolipoprotein A1 concentration rather than cholesterol alone.
Long-Term Outcome of Paediatric Patients with Hereditary Tubular Disorders
Authors: Haffner D. , Weinfurth A. , Manz F. , Schmidt H. , Bremer H.J. , Mehls O. , Schärer K.
Published: April 2003

Background: An increasing number of children with hereditary tubular disorders (HTD) reach adult life due to diagnostic and therapeutic advances which results in growing need to manage these patients by adult centres. Data on the prevalence and the late clinical problems of these patients are limited. Methods: We observed 177 paediatric patients with isolated or complex HTD between 1969 and 1994. The median age at the time of diagnosis was 3 (range 0–18) years and the median observation period 10 (range 1–43) years. The long-term outcomes with respect to renal function, bone disease, and body growth were analyzed. Results: The prevalence of HTD was 3.2% of all patients observed in our renal unit and 14% of those patients with chronic renal failure and/ or end-stage renal disease. The three most frequent disorders observed were nephropathic cystinosis (n = 34), X-linked hypophosphataemic rickets (n = 26), and idiopathic hypercalciuria (n = 17). At the last observation, 12% of the patients with isolated HTD and 30% of those with complex HTD had developed preterminal chronic renal failure; end-stage renal disease was observed in 5 and 25%, respectively (p < 0.001). Progressive disease occurred mainly in patients having cystinosis, primary hyperoxaluria, the syndrome of hypomagnesaemia/hypercalciuria, primary Fanconi syndrome, Fanconi-Bickel syndrome, and methylmalonic aciduria. Nephrocalcinosis was found in 42%, urolithiasis in 14%, bone deformities and/or fractures in 28%, and other extrarenal alterations in 29% of all patients. The median body height at last observation was 2.0 SD below the normal mean (range from –10.4 to +2.6), and the adult height was subnormal in 48% of 67 grown-up patients. Growth retardation was more severe in complex than in isolated HTD. The mortality decreased from 17% in 1969–1981 to 12% in 1982–1994. Conclusion: Although HTD are rare nephropathies, their frequently progressive course associated with extrarenal complications requires the attention of nephrologists beyond the paediatric age.
Relationship between Gingival Hyperplasia and Class II Histocompatibility Antigens in Renal Transplant Recipients
Authors: Türkmen Aydın , Ak Gülsüm , Furuncuoglu Yavuz , Akar Uǧur , Seyhun Yalçın , Türk Süleyman , Çarin Mahmut , Sever M. Şükrü
Published: April 2003

Gingival hyperplasia, a well-known side effect of ciclosporin A (CS-A), is much more prominent when CS-A is used in combination with calcium channel blockers, especially dihydropyridines. On the other hand, it is interesting to note that this complication is not observed in all patients using this drug combination. This study was conducted in order to investigate the relationship (if any) between major histocompatibility complex antigens and gingival hyperplasia. Seventy-six renal transplantation patients were evaluated by an experienced dentist for gingival hyperplasia. The patients were then divided into two groups according to the presence (group 1, n = 18) or absence (group 2, n = 58) of gingival hyperplasia. There was no significant difference between the two groups regarding age, sex, transplant age, donor type, antihypertensive and immunosuppressive therapy protocols, and CS-A levels. HLA-DR2 antigen was present in 63% of the patients with gingival hyperplasia and in 34% of the patients without gingival hyperplasia. However, the HLA-DR1 antigen frequencies were found to be 11 and 22% in group 1 and group 2, respectively. In patients receiving nifedipine as an antihypertensive therapy, gingival hyperplasia developed more often than in patients receiving verapamil or diltiazem. As a result, in renal allograft recipients with HLA-DR1 antigen, gingival hyperplasia was seen less frequently than in HLA-DR2-positive patients. It is believed that the presence of these antigens regulates the response of the patients to either CS-A and/or calcium channel blockers.
Glomerular Extracellular Matrix Accumulation in Experimental Anti-GBM Ab Glomerulonephritis
Authors: Tang Winson W. , Feng Lili , Loskutoff David J. , Wilson Curtis B.
Published: April 2003

Thickening of the glomerular basement membrane (GBM) results from excessive accumulation of extracellular matrix (ECM) proteins following glomerular injury. We studied the temporal relationship between the expression of growth factors, ECM accumulation, ECM degrading proteinases, and their inhibitors in a rat model of anti-GBM antibody (Ab) glomerulonephritis (GN) by the RNase protection assay and immunohistochemistry. There were two- or fourfold increases in the expression of transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) A and B chain mRNAs 4 days after anti-GBM Ab administration. These changes were temporally associated with increased accumulation of α1(III) and α2(IV) collagens, fibronectin, and heparan sulfate proteoglycan along the GBM. The increase in matrix accumulation was associated with little or no increases in the proteinases, urokinase plasminogen activator (u-PA) and transin, respectively. There was a 1.6× increase in the u-PA/28s mRNA ratio on day 4 in rats with anti-GBM Ab GN, but this was not associated with an increase in u-PA biologic activity. By comparison, the mRNAs of the proteinase inhibitors, plasminogen activator inhibitor-1 (PAI-1) and tissue inhibitor of metalloproteinase (TIMP) were 5× greater than that of control rats on day 4. PAI-1 mRNA correlate with increased biologic activity. These data demonstrate a temporal association between TGF-β1 and PDGF expression and matrix accumulation within the GBM in anti-GBM Ab GN. In addition, it suggest that this matrix accumulation results from an imbalance between matrix synthesis and degradation.
Restoration of Impaired T-Cell Proliferation after Parathyroidectomy in Hemodialysis Patients
Authors: Tzanno-Martins C. , Futata E. , Jorgetti V. , Duarte A.J.S.
Published: April 2003

Background/Aims: Severe secondary hyperparathyroidism is not infrequent in hemodialysis patients and recent studies suggest that parathyroid hormone (PTH) may play a role in the genesis of cell immunity abnormalities in uremia. The aim of the present study is to describe the effect of parathyroidectomy on T- and B-cell functions in hemodialysis patients. Methods: The study was performed on 6 patients with severe secondary hyperparathyroidism. iPTH, B, CD4+, CD8+, total number of lymphocytes, lymphoproliferative response to PHA, PWM and Candidin, and IgG, IgM, IL-2 production in vitro were determined 1 day before and 4 months after parathyroidectomy. Results: The lymphoproliferative response to PHA increased significantly after parathyroidectomy. We also observed a trend to an increase in production of IgG and IgM after PWM stimulation before therapy. Conclusion: The present study suggests that patients with extremely high levels of PTH show a complete restoration of impaired T-cell proliferation after parathyroidectomy.
Heparin Treatment Reduces Glomerular Injury in Rats with Adriamycin-Induced Nephropathy but Does Not Modify Tubulointerstitial Damage or the Renal Production of Transforming Growth Factor-Beta
Authors: Baroni Edmara A. , Costa Roberto S. , da Silva Cleonice G.A. , Coimbra Terezila M.
Published: April 2003

In this study we investigated the effect of heparin on renal injury and renal transforming growth factor-β (TGF-β) production in adriamycin (AD)-injected rats. Thirty-nine female Wistar rats were injected with AD (3.5 mg/kg body weight, i.v.) and 27 with 0.15 M NaCl solution (group C). Fifteen days later we started to inject heparin, 500 U/day, s.c., in 20 of the AD-injected animals (AD-H group). Three months after beginning treatment, urine samples were collected to quantify albumin, creatinine and TGF-β. The rats were killed and the kidneys removed for histological, immunohistochemical, ELISA and RNA studies. All AD-injected animals showed structural renal changes (p < 0.05). However, the glomerular alterations were less intense in rats from group AD-H (p < 0.05). The percentage of glomerulosclerosis was 0.11 ± 0.08 in group C, 14.7 ± 12.8 in group AD (treated only with AD) and 3.42 ± 2.3 in group AD-H. Renal cortex immunostaining for TGF-β and mRNA content of this polypeptide was higher in both groups of animals injected with AD compared to controls (p < 0.05). These animals also presented a higher rate of urinary TGF-β excretion (p < 0.05), which was 202 ± 11 in group C, 1,103 ± 580 in group AD and 1,564 ± 328 pg/mg Ucreat in group AD-H. However, TGF-β activity in the glomerular-conditioned media from the rats of group AD was higher than in the glomerular-conditioned media from the rats of group AD-H. In conclusion, treatment with heparin reduces glomerular damage in rats with AD-induced nephropathy but does not modify tubulointerstitial lesions or the renal production of TGF-β.
Importance of Serotonergic Mechanisms in the Thrombotic Complications in Hemodialyzed Patients Treated with Erythropoietin
Authors: Małyszko Jacek S. , Małyszko Jolanta , Pawlak Krystyna , Pawlak Dariusz , Buczko Włodzimierz , Myśliwiec Michał
Published: April 2003

So far it is not clear how erythropoietin affects the anticoagulant properties of vascular endothelium in uremia. Since serotonin is also thought to play a role in the pathogenesis of thrombosis, the aim of the study was to evaluate major components of extrinsic coagulation pathway, markers of endothelial cell injury, lipoprotein (a) and peripheral serotonergic mechanisms during rHuEPO therapy in hemodialyzed patients. The study was performed on chronically hemodialyzed patients divided into two groups: with rHuEPO treatment and without rHuEPO therapy in relation to the control group. In uremic patients, thrombomodulin and von Willebrand factor, activity of factor VII, tissue factor pathway inhibitor (TFPI) activity, TFPI and tissue factor (TF) concentrations, lipoprotein (a) level were significantly higher when compared to healthy volunteers. Treatment with rHuEPO resulted in a further significant rise in markers of endothelial cell injury: thrombomodulin and von Willebrand factor and TFPI concentration. Extrinsic coagulation factors: activities of factor VII and X, TFPI activity and TF activity and concentration, lipoprotein (a) and vitronectin remained unchanged during rHuEPO therapy. Platelet serotonin content and whole blood serotonin were significantly lower in uremic patients relative to healthy volunteers and during rHuEPO treatment they increased significantly. Whole blood serotonin reached normal values. Plasma serotonin, significantly elevated in uremia, did not change during rHuEPO therapy. Serotonin uptake by uremic platelets was significantly impaired and remained unaltered during rHuEPO administration. Serotonin release by uremic platelets was also significantly depressed but a significant improvement was observed in rHuEPO-treated patients. Our data suggest that endothelial injury, TF pathway components and peripheral serotonergic system disturbances may predispose to thromboembolic complications and play a role in the pathogenesis of atherosclerosis in uremic patients, particularly treated with rHuEPO. Increase in TFPI may compensate the increase in TF in these patients.
Structural Analysis of Human β-Defensin-1 and Its Significance in Urinary Tract Infection
Authors: Hiratsuka Takeaki , Nakazato Masamitsu , Ihi Toshihiko , Minematsu Toshio , Chino Naoyoshi , Nakanishi Toyofumi , Shimizu Akira , Kangawa Kenji , Matsukura Shigeru
Published: April 2003

Human β-defensin-1 (hBD-1) is a 36-amino-acid antimicrobial peptide that functions in the host innate defense. We developed a highly sensitive radioimmunoassay for hBD-1 and identified several hBD-1 peptides in human kidney, urine, and plasma by amino acid sequencing and mass spectrometry. Large quantities of hBD-1 peptides are produced in the kidney, are released into the tubular lumen as 47-amino-acid pro-hBD1, and then undergo proteolytic processing and generate multiple truncated forms. The respective urine and plasma concentrations of hBD-1 in patients with pyelonephritis are 48.1 ± (SEM) 15.7 pmol/mg creatinine and 2.66 ± 0.41 pmol/ml, 3.1-fold and 1.8-fold those of normal individuals. hBD-1 is thought to contribute to mucosal defense in the urinary tract. Our findings provide a better understanding of the biosynthesis of this peptide and its pathophysiological significance in infectious diseases.
Expression of Heat Shock Proteins 72/73 in Human Peritoneal Mesothelial Cells in vivo and in vitro
Authors: López-Cotarelo Cristina , Sellhaus Bernd , Baba Hideo Andreas , Manegold Edith , Luka Johanna , Handt Stefan , Mittermayer Christian , Klosterhalfen Bernd , Tietze Lothar
Published: April 2003

Leukocyte accumulation during peritonitis leads to an injurious microenvironment which is involved in the host defense reaction but is also thought to cause peritoneal damage. We tested the hypothesis that mesothelial cells (MC) respond to the injurious microenvironment during peritonitis by an increased expression of heat shock proteins (HSP 72/73), a basic way by which cells are protected against injury. Comparison of resting MC and activated MC during peritonitis in vivo by means of immunohistochemistry revealed an increased expression of HSP 72/73. As assessed by Western immunoblotting, incubation of MC in vitro with tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) caused a time-dependent induction of HSP 72/73 expression, which was maximal 6 h after stimulation. We suggest that the increased HSP 72/ 73 expression of MC during peritonitis is in part induced by TNF-α and IL-1β and may exert a cell-protective function, lessening MC damage during peritonitis.
Melatonin, a Pineal Hormone with Antioxidant Property, Protects against Gentamicin-Induced Nephrotoxicity in Rats
Authors: Shifow A.A. , Kumar K.V. , Naidu M.U.R. , Ratnakar K.S.
Published: April 2003

The present study investigated the effects of melatonin, an antioxidant, on gentamicin-induced nephrotoxicity in rats. Melatonin (5 mg/kg p.o.) was used 3 days before and 8 days simultaneously with gentamicin (80 mg/kg i.p.) Saline-treated animals served as controls. Determinations of urinary creatinine, N-acetyl-β-D-glucosaminidase, glucose, protein, blood urea, serum creatinine, plasma and kidney tissue malondialdehyde (MDA), and antioxidant enzyme levels in kidney tissue were done after 8 days of gentamicin treatment. The kidneys were also examined for morphological changes using histological techniques. Gentamicin caused nephrotoxicity as evidenced by marked elevation in blood urea and serum creatinine. Mean blood urea and serum creatinine levels were 289 ± 50, and 2.5 ± 0.5 mg/dl, respectively, in rats treated with gentamicin. Melatonin significantly protected the rats from gentamicin-induced nephrotoxicity; blood urea and serum creatinine levels were 23 ± 2.7 and 0.88 ± 0.19 mg/dl, respectively. The creatinine clearance was decreased with gentamicin treatment (0.048 ± 0.007 ml/min) as compared with controls (0.41 ± 0.08 ml/h/kg). In rats treated with melatonin plus gentamicin, the creatinine clearance was similar to controls (0.41 ± 0.08 ml/h/kg). The product of lipid peroxidation (MDA) was markedly increased in plasma (2.10 ± 0.15 nmol) and kidney tissue (8.87 ± 3.2 nmol/mg protein) with gentamicin treatment. Melatonin prevented the gentamicin-induced rise in plasma MDA (1.03 ± 0.27 nmol) and kidney tissue MDA (2.57 ± 0.87 nmol/mg protein). An increased excretion of urinary N-acetyl-β-D-glucosaminidase, glucose, and protein by gentamicin was also prevented by melatonin. Kidneys from gentamicin-treated rats showed tubular epithelial loss with intense granular degeneration involving more than 50% of renal cortex, while there were findings comparable to controls in melatonin plus gentamicin treated rats. The present study indicates that melatonin significantly protects against gentamicin-induced renal toxicity in Wistar rats.
Increased Maintenance Corticosteroids during Upper Respiratory Infection Decrease the Risk of Relapse in Nephrotic Syndrome
Authors: Mattoo Tej K. , Mahmoud Mustapha A.
Published: April 2003

Relapses are common in children with idiopathic nephrotic syndrome, and this prospective study looks into the possibility of decreasing the frequency of relapses in a selected group of such patients. The study includes 36 children with a steroid-dependent, relapsing nephrotic syndrome on a maintenance prednisone therapy of about 0.5 mg/kg every other day. They were prospectively divided into two groups with comparable age and sex distribution and the number of those who had previously received cyclophosphamide therapy. Group 1 patients were advised to take daily prednisone for 5 days, starting at the time of the onset of an upper respiratory tract infection (URI). No such advice was given to those in group 2, and they remained on alternate-day prednisone during URI. At the end of a 2-year follow-up period, the total number of relapses in group 1 was 40 with a mean of 2.2 ± 0.87 per patient as compared with 99 with a mean of 5.5 ± 1.33 per patient in group 2 (p = 0.04). We conclude that an increased maintenance prednisone during URI helps decrease significantly the number of relapses in those on alternate-day therapy.
Morbidity and Mortality Reduction Associated with the Use of Erythropoietin
Authors: Tsakiris Dimitrios
Published: April 2003

Aim: The aim of this paper is to review the emerging evidence supporting erythropoietin therapy in improving the long-term prognosis of patients with renal failure, by correcting underlying anaemia. Methods: This paper reviews and discusses data from several large retrospective databases containing the demographic and treatment details of many thousands of patients with renal insufficiency. Each investigation selected for review used appropriate statistical methodologies to determine the effects of erythropoietin on morbidity and mortality. Results: There is a clear link between anaemia and the development of cardiovascular dysfunction. This is an important finding given that more than 90% of patients become anaemic as a consequence of renal failure. Database analysis has also shown that treatment of anaemic dialysis patients with erythropoietin significantly reduces mortality, often by more than 20%, primarily through effects on the cardiovascular system. In addition, improvements in the exercise capacity and quality of life of patients have been observed despite many patients entering dialysis with a considerable burden of ill health, particularly cardiovascular dysfunction. Conclusions: Retrospective database analyses have provided a clear understanding of the advantageous effects of erythropoietin treatment on morbidity and mortality in patients with end-stage renal disease. The implications of these findings for further improving treatment strategies in patients with renal insufficiency point to erythropoietin use before the onset of dialysis.
Increased Plasma Levels of Mature Adrenomedullin in Chronic Glomerulonephritis
Authors: Kinoshita Hiroshi , Fujimoto Shouichi , Kitamura Kazuo , Matsuura Yuka , Uezono Shigehiro , Hisanaga Shuichi , Eto Tanenao
Published: April 2003

Adrenomedullin (AM) is a potent vasodilative and natriuretic peptide that is processed from its precursor as the intermediate form, AM-glycine-COOH (iAM). Subsequently, iAM is converted to the biologically active mature form, AM(1-52)-CONH2 (mAM), by enzymatic amidation. Using immunoradiometric assays that recognize total AM (tAM) and only mAM, we determined the plasma and urinary levels of mAM and iAM in patients with chronic glomerulonephritis (CGN). The plasma mAM concentration was significantly higher in the patients than in the controls (1.8 ± 0.1 vs. 1.3 ± 0.1 fmol/ml, p < 0.01), whereas the plasma iAM concentration of the CGN patients did not significantly differ from that of the controls (9.4 ± 0.5 vs. 8.9 ± 0.5 fmol/ml). Levels of urinary mAM excretion in the patients did not statistically differ from those of the controls (1.6 ± 0.4 vs. 2.0 ± 0.3 fmol/mg creatinine), whereas urinary iAM excretion was significantly lower in the CGN patients (3.7 ± 0.7 vs. 5.6 ± 0.8 fmol/mg creatinine, p < 0.05). Urinary excretion levels of mAM significantly correlated with those of sodium (r = 0.47, p < 0.05), whereas those of iAM did not. In conclusion, the plasma ratio of mAM to iAM is augmented in CGN patients, and mAM appears to be involved in the regulation of sodium. Therefore, determination of the mAM in addition to the tAM concentration is essential in CGN patients.
Cell and Molecular Biology of Organic Osmolyte Accumulation in Hypertonic Renal Cells
Authors: Handler Joseph S. , Kwon H. Moo
Published: April 2003

When the renal medulla becomes hypertonic in association with the formation of concentrated urine, the cells of the medulla avoid the stress of high intracellular salts by accumulating small non-perturbing organic osmolytes. The response has been studied in most detail in cultured kidney-derived cells, and confirmed in studies of the intact kidney. The non-perturbing osmolytes, myo-inositol, betaine, and sorbitol, are accumulated because of stimulation of the transcription of the genes for the proteins that catalyze their accumulation by transport or synthesis. The genes involved have all been cloned and sequenced and contain tonicity responsive regulatory elements (TonEs) in their 5′ region. During hypertonicity, the elements are occupied by TonE-binding protein, a transacting factor that has been cloned and characterized. Current efforts focus on identifying the mechanism by which cells sense hypertonicity and how that leads to activation of TonE-binding protein.
Haemodialysis and Cerebral Oedema
Authors: Walters R.J.L. , Fox N.C. , Crum W.R. , Taube D. , Thomas D.J.
Published: April 2003

Background: Haemodialysis may cause neurological symptoms ranging from inconvenient feelings of disequilibrium to life-threatening neurological complications. There are animal data to suggest cerebral swelling may accompany haemodialysis and contribute symptomatically to dialysis disequilibrium. However, MR images acquired following haemodialysis often fail to demonstrate evidence of cerebral oedema. We wished to quantify any potential cerebral volume change which is caused by haemodialysis treatment. Method: Five renal patients and 5 control subjects had a two volumetric T1-weighted MRI scans on the same day. The patients were imaged immediately before and after haemodialysis. None were taking steroids. Precise positional matching (registration) was used to quantify cerebral volume change. Results: Patients had an increase in cerebral volume following dialysis which averaged 32.8 ml (SE 7.4 ml, 3% brain volume). The change in the controls was 1.4 ml (SE 0.6 ml), p < 0.001. No patient had significant neurological symptoms. Conclusion: Cerebral oedema developed in the patients following dialysis. There is a good biological model for these observations. Modifications to dialysis may help. Common problems which increase cerebral volume, e.g. acute stroke, require careful appraisal in these patients. These observations need consideration when quantifying atrophy in dialysis patients.
Cyclosporine-Associated Thrombotic Microangiopathy during Daclizumab Induction: A Suggested Therapeutic Approach
Authors: Trimarchi H. , Freixas E. , Rabinovich O. , Schropp J. , Pereyra H. , Bullorsky E.
Published: April 2003

A woman on daclizumab developed thrombotic microangiopathy secondary to cyclosporine after a living-unrelated kidney transplant. Despite cyclosporine discontinuation, hemolysis persisted. The second dose of daclizumab was postponed 24 h, and after a maximum of two sessions of plasmapheresis (to avoid further modifications in daclizumab schedule) with plasma exchange, daclizumab was administered. Plasma infusions were prescribed until D-dimer and fibrinogen-degradation products normalized; thereafter, FK-506 was started without recurrence of the hemolytic picture and renal function restored. This observation suggests that in patients on daclizumab who develop thrombotic microangiopathy secondary to immunosuppressants, if discontinuation of the offending drug is unsuccessful, plasmapheresis with plasma exchange can be performed when the lowest levels of daclizumab exist, followed by daclizumab infusion. Plasma prescription must be continued thereafter until D-dimer and figrinogen-degradation products normalize. However, if hemolysis persists when daclizumab levels are high, plasma infusions are useful and plasmapheresis avoided. FK-506 administration did not result in recurrence of hemolysis during daclizumab induction.
Tuberculosis in Maintenance Dialysis Patients
Authors: Chou Kang-Ju , Fang Hua-Chang , Bai Kuan-Jen , Hwang Shang-Jyh , Yang Wu-Chang , Chung Hsiao-Min
Published: April 2003

In this investigation, we tried to find the incidence and characteristics of tuberculosis (TB) in dialysis patients previously found only in a small number of cases. We collected the cases of newly diagnosed TB patients in Taiwan during 1997. Simultaneously, all dialysis patients were collected and matched with the TB cases to identify the dialysis patients who had also contracted TB. The annual incidence of the dialysis population was 493.4/100,000, 6.9 times that of the general population (71.1/100,000). The annual incidence for the male dialysis population was 573.3, the incidence was 479.2 for the female dialysis population. The incidence for the general population was 97.1 and 43.7/100,000, respectively. Although the 1-year mortality rate due to TB (1.7 vs. 1.9%, p > 0.05) was similar in both populations, the non-TB mortality was much higher in the dialysis population than that in the general population (25.6 vs. 11.1%, p < 0.05). Finally, the 1-year mortality rate of dialysis patients with TB is 3.3 times higher than that in dialysis patients without TB (27.3 vs. 8.3%, p < 0.05). The findings suggest that uremia modifies the behavior of TB, jeopardizes female and younger dialysis patients, poses a higher risk of extrapulmonary dissemination, and predicts a higher overall mortality.
Treatment of Severe Hypothyroidism Reduced Serum Creatinine Levels in Two Chronic Renal Failure Patients
Authors: Nakahama Hajime , Sakaguchi Katsuhiko , Horita Yoshio , Sasaki Osamu , Nakamura Satoko , Inenaga Takashi , Takishita Shuichi
Published: April 2003

Short-term hypothyroidism has been associated with a reversible rise in serum creatinine levels in patients with normal renal function. A remarkable decline in serum creatinine levels associated with a treatment of severe and prolonged hypothyroidism has rarely been reported so far. We present here 2 patients with chronic renal failure in whom treatment for hypothyroidism resulted in a significant and sustained reduction of their serum creatinine levels. These cases indicate that because hypothyroidism may aggravate the serum creatinine levels, TSH should be considered in screening procedures of patients with chronic renal failure presenting with recent accelerated aggravation of renal function. Hypothyroidism per se, one of its complications or one of its associated autoimmune diseases might play a role in modifying the underlying renal problem.
Urinary Copper Excretion in Type 2 Diabetic Patients with Nephropathy
Authors: Ito Seiki , Fujita Hiroki , Narita Takuma , Yaginuma Toshiko , Kawarada Yoshihiko , Kawagoe Masami , Sugiyama Toshihiro
Published: April 2003

Background/Aims: The aim of this study was to examine the relationship between the degree of urinary copper excretion and stages of diabetic nephropathy. Methods: Copper, ceruloplasmin and albumin concentrations were measured in serum and urine samples from 41 type 2 diabetic outpatients with different stages of nephropathy and from 10 healthy controls. The copper/albumin and copper/ceruloplasmin ratios in serum and urine were determined. Furthermore, we examined whether free copper ions are dissociated from ceruloplasmin under various pH conditions. Results: Urinary copper concentrations significantly increased only in macroalbuminuric patients. The copper/ceruloplasmin and copper/albumin ratios in urine were consistently greater than those in serum which were not different between patients and healthy controls except the copper/albumin ratio in macroalbuminuric patients. The ratios in urine decreased in parallel with the progression of nephropathy. Copper was found to be released from ceruloplasmin under acidic conditions. Conclusion: Urinary copper excretion in healthy controls may be the result of dissociation from the albumin-copper complex of serum during its passage through the kidney. In diabetic patients with advanced nephropathy, urinary copper excretion may be due to dissociations from both copper-albumin and ceruloplasmin-copper complexes filtered through the damaged glomerulus. Overloading of urinary copper to damaged renal tubules may play some roles in the progression of nephropathy in patients with advanced nephropathy.
Study on Concretions Developed around Urinary Catheters and Mechanisms of Renal Calculi Development
Authors: Grases F. , Söhnel O. , Costa-Bauzá A. , Ramis M. , Wang Z.
Published: April 2003

Aims: To study the structure and composition of encrustation and concretions developed on urinary catheters to better understand their formation mechanism to be able to prevent them. Methods: The surface of catheters was studied by direct and scanning electron microscopy observation. In vitro formation of encrustations was performed in synthetic urine. Results: The surface of catheters was covered by a continuous layer of organic matter, on which a thin scale consisting of crystals of calcium oxalate monohydrate (COM), uric acid anhydrous or calcium phosphate developed. Encrustations observed on catheters generally exhibited the same composition as the previously developed renal calculi. In catheters collected from patients without previous episodes of renal calculi or with previous episodes of infected renal calculi in which infection was afterwards eradicated, on the first organic layer, in that case plate-like COM crystals forming a columnar layer were observed. In vitro experiments demonstrated that COM columnar structures were only formed when normocalciuric urine containing organic matter was used, and the presence of crystallization inhibitors, as phytate, notably delayed their formation. Conclusion: Calcium oxalate was the main crystalline phase developed on catheters inserted in patients, specially in the absence of urinary infection or urinary pH values <5.5 and high urinary uric acid levels. Thus, prophylaxis of encrustations may consist of preventive measures usually applied in cases of recurrent idiopathic calcium oxalate urolithiasis.
Characterization of Aldose Reductase from the Thick Ascending Limb of Henle’s Loop of Rabbit Kidney
Authors: Grunewald R. Willi , Eckstein Angela , Reisse Claudius H. , Müller Gerhard A.
Published: April 2003

Background: The organic osmolyte sorbitol plays an important role in the osmoregulation of immortalized epithelial cells of the thick ascending limb of Henle’s loop (TALH) of rabbit. The intracellular sorbitol content seems to depend strongly on the extracellular osmolarity. To investigate the nature of the osmotic regulation we characterized the aldose reductase. Methods: We determined aldose reductase activity enzymatically and the content of organic osmolytes by HPLC. Results: The aldose reductase activity correlates with the extracellular tonicity. Elevating the osmolarity of the medium from 300 to 600 mosm/l by addition of NaCl or sucrose resulted in a significant increase of maximal velocity (Vmax) of the adapted cells from 8 ± 1 µmol/g × min (300 mosm/l) to 322 ± 28 µmol/g × min (600 mosm/l, NaCl) or 54 ± 9 µmol/g × min (600 mosm/l, sucrose), respectively, while affinity (Km) remained unchanged. But we found no rise of aldose reductase activity when extracellular urea concentration was elevated. Similar alterations in Vmax were observed when the activity of the highly enriched enzyme was determined with glucose as substrate. Elevation of the extracellular osmolarity by NaCl and sucrose strongly induced the expression of aldose reductase protein with an apparent molecular weight of 39 kD. The affinity of glucose is characteristically low with a Km above 300 mmol/l. Aldose reductase utilizes both NADPH and with lower affinity NADH as coenzymes. In vitro sulfate ions (0.4 mol/l) results in a two-fold activation of the aldose reductase activity whereas sodium (200–400 mmol/l) decreased the activity significantly (22–33%). Potassium and chloride up to 400 mmol/l did not alter the aldose reductase activity in vitro. Conclusions: These results indicate that the aldose reductase of TALH cells of the outer medulla is osmotically regulated and has many similarities with aldose reductase in renal inner medulla. Therefore, intracellular sorbitol synthesis seems to be of similar importance in the osmoregulation of TALH cells as in the inner medulla.
Pregnancy Outcome in Nephrotic Syndrome with Mixed Connective Tissue Disease
Authors: Horita Yoshio , Tsunoda Sei , Inenaga Takashi , Kawano Yuhei , Ishibashi-Ueda Hatsue , Chiba Yoshihide , Takishita Shuichi
Published: April 2003

We describe two pregnancies of a young woman with mixed connective tissue disease. In June 1983, she was diagnosed as having Raynaud’s phenomenon, arthralgia, and proteinuria. She then developed nephrotic syndrome. Methylprednisolone was initially prescribed at a large dose of 1 g/day which was slowly tapered to 5 mg/day. The proteinuria disappeared. During both pregnancies (the first beginning in December 1988 and the second in May 1992), the patient was placed on a prednisolone maintenance dose (5 mg/day). Both neonates were born healthy at term with no complications. Continuing prednisolone may be useful in pregnant women, and aggressive treatment to prevent mixed connective tissue disease exacerbation may be appropriate during pregnancy.
Salt, Kidney and Hypertension: Why and What to Learn from Genetic Analyses?
Authors: Kurokawa Kiyoshi
Published: April 2003

The relation between salt intake and high blood pressure has been widely recognized, but its exact mechanisms and the reason of such a relation are not clearly understood. In this review, I discuss the sequence of factors relevant to our understanding of the pathophysiology of ‘essential’ hypertension. I will first consider the relation between two major determinants of systemic blood pressure, i.e. extracellular fluid volume (ECFV) and the renin-angiotensin-aldosterone system, and then the renal sensing mechanism of changes in ECFV, the historical background of salt intake in our culture, and finally suggest explanations of results of genetic analyses of hypertension. The discussion is aimed at furthering our understanding of how and why hypertension develops in response to present day high salt intakes. In addition, data are presented for the implementation of a practical health care policy to effectively reduce the incidence of hypertension.
Pathophysiology of Perinatal Brain Damage
Authors: Evrard Philippe
Published: April 2003

Brain damage in the premature or full-term fetus or newborn infant encompasses multiple patterns of injury, many considered to be anomalous in origin. However, there is increasing evidence that such congenital lesions arise as a consequence of hypoxia or ischemia (reperfusion failure). Animal models have been helpful in elucidating the underlying cellular and molecular mechanisms responsible for perinatal brain damage. Ultimately, neuroprotective strategies will prevent or minimize the occurrence of these lesions and their consequent functional deficiencies.
Delayed Cerebral Atrophy following Moderate Hypoxia-Ischemia in the Immature Rat
Authors: Geddes Rastafa , Vannucci Robert C. , Vannucci Susan J.
Published: April 2003

Hypoxia-ischemia (H/I) damages cells in the immature brain and interferes with subsequent brain development; the extent of the damage has been related to the severity, or duration, of the initial insult. This study examined the effects of both severe and moderate duration of H/I on the evolution of damage through 8 weeks of recovery. Seven-day-old rat pups were subjected to either 75 min or 2 h of 8% oxygen following a unilateral carotid artery ligation. Evaluation of brain damage included morphometric analysis of hemispheric diameter at 2, 4, and 8 weeks of recovery, and hematoxylin and eosin for evaluation of pathology at 8 weeks. Two hours of H/I produced severe infarction in the ipsilateral hemisphere in the majority of the survivors, apparent by 2 weeks of recovery with no change at 4 or 8 weeks. In marked contrast, 75 min of H/I produced no significant damage during the initial 2 weeks of recovery but resulted in progressive cerebral atrophy with delayed infarction such that the extent of damage at 8 weeks was not different from the 2-hour group. Thus, even a mild-moderate ischemic insult to the perinatal brain establishes a vulnerable region which ultimately dies without intervention.
Neurodegeneration in the Thalamus following Neonatal Hypoxia-Ischemia Is Programmed Cell Death
Authors: Northington Frances J. , Ferriero Donna M. , Martin Lee J.
Published: April 2003

We studied neuronal cell body, axonal, and terminal degeneration in brains from 7-day-old rat pups recovered for 0, 1.5, 3, 6, 24, 48, 72 h, and 6 days following hypoxia-ischemia and identified proteins involved in the delayed neurodegeneration in the thalamus. We found that injury is biphasic with initial necrosis in the ipsilateral forebrain by 3 h following hypoxia-ischemia, in contrast to more delayed and apoptotic-like injury in the ventral-basal thalamus, brainstem, and other remote non-forebrain regions. Prior to the appearance of large numbers of apoptotic profiles in the ventral-basal thalamus, expression of Fas death receptor protein, activated forms of caspase 8 and caspase 3, and pro-apoptotic Bcl-2 proteins are increased. This manuscript combines our data on hypoxic-ischemic injury in the developing brain and presents evidence for at least two forms of neurodegeneration, namely, acute necrosis in the forebrain and delayed neurodegeneration in the thalamus, which is death-receptor-mediated programmed cell death.
High-Rising Terminals and Fall-Rise Tunes in Australian English
Authors: Fletcher Janet , Harringtonb Jonathan
Published: April 2003

It is usually claimed that statement high rises in Australian English are more or less phonetically identical to yes/no question rises. In this paper, statement high rises and question rises were examined in a corpus of controlled spontaneous speech (i.e. map task dialogues) to see if this is the case. It appears that speakers in this study used different kinds of rises for declaratives and questions. The majority of statement high rises were realized with a low pitch accent onset, whereas almost all question rises were produced with high pitch accent onsets. High-range fall-rises also appeared to be used by some speakers in the same way as statement high rises. Implications of these findings for the current ToBI analysis of Australian English are considered.
Effects of Long-Term Treatment with Simvastatin on Some Hemostatic Parameters in Continuous Ambulatory Peritoneal Dialysis Patients
Authors: Małyszko Jolanta , Małyszko Jacek S. , Hryszko Tomasz , Myśliwiec Michał
Published: April 2003

Background/Aim: Disturbances in serum lipids, hemostasis and platelet functions are frequent features in uremia and may contribute to the progression of atherosclerosis and its thrombotic complications. Recently, attention has been paid to beneficial effects of statins on serum lipids and hemostasis in uremic patients. Peritoneally dialyzed (continuous ambulatory peritoneal dialysis; CAPD) subjects are particularly prone to dyslipidemia and have a high risk of cardiovascular death. The purpose of this work was to assess platelet functions, some hemostatic parameters and serum lipids in 8 hyperlipidemic CAPD patients treated with simvastatin (Zocor, MSD) for 6 months. Methods: Platelet aggregation in whole blood and in platelet-rich plasma (PRP) induced by collagen (2 µg/ml for whole blood and PRP), arachidonic acid (0.75 mM for whole blood and PRP), ADP (10 µM for whole blood and 5 µM for PRP) and ristocetin (0.75 mg/ml for whole blood and 1.5 mg/ml for PRP) was studied before and after 1, 3 and 6 months of simvastatin (dose: 10 mg at bedtime) treatment. Results: Whole-blood platelet aggregation induced by collagen decreased significantly after 3 and 6 months of the therapy, whereas in PRP, platelet aggregation induced by collagen and ADP decreased significantly after 6 months. Ristocetin-induced platelet aggregation in PRP decreased significantly after 3 and 6 months of simvastatin therapy. P-selectin remained unaltered by 6 months of simvastatin therapy. The fibrinolytic activity index was significantly higher after 3 months of the therapy when compared to the baseline values. Thrombomodulin, a marker of endothelial cell injury, was significantly lower after 3 and 6 months of the therapy. Prothrombin fragments 1 + 2 did not change significantly during 6 months of simvastatin administration. Cholesterol and LDL fell significantly as early as after 1 month and remained lowered during further months of the therapy. Conclusion: Simvastatin is an effective hypolipemic agent and favorably affects platelet aggregation, endothelial function and fibrinolysis in CAPD patients.
Response to Shiga Toxin-1, with and without Lipopolysaccharide, in a Primate Model of Hemolytic Uremic Syndrome
Authors: Siegler Richard L. , Pysher Theodore J. , Lou Randall , Tesh Vernon L. , Taylor Jr. Fletcher B.
Published: April 2003

Shiga toxin (Stx) and lipopolysaccharide (LPS) both participate in the pathogenesis of post-diarrheal hemolytic uremic syndrome (HUS), yet little is known about the factors that modulate the host response to these toxins. We have previously shown that the baboon develops HUS if 100 ng/kg of purified Stx-1 is administered rapidly as a single bolus, but not if it is given as four 25-ng/kg doses every 12 h. We therefore used this baboon model to study the response to small intravenous doses of Stx-1, with and without the co-administration of LPS. The co-administration of two 1-mg/kg doses of LPS (given at 0 and 24 h) and four 25-ng/kg doses of Stx-1 (given at 0, 12, 24, and 36 h) resulted in HUS, but the administration of either toxin separately did not. The development of HUS was associated with a rise in urinary, but not plasma concentrations of TNF, and a rise in both urinary and plasma concentrations of IL-6 and IL-8. We speculate that LPS is not required for disease expression in the human, but that it can augment the response to otherwise subtoxic amounts of Stx and this augmentation may be mediated by LPS-induced cytokine release.