bluuebunny/crossref_metadata_2025 huggingface dataset:
Appropriate Dosing of Pilsicainide Hydrochloride in Patients on Hemodialysis
Authors: Matsumoto Machiko , Fujii Zenzo , Kawata Yasunobu , Sakumura Toshihiro , Minami Masae , Fujimoto Kiyoko , Nawata Chieko , Matsuzaki Masunori
Published: April 2003

Appropriate dosing of pilsicainide hydrochloride, an anti-arrhythmic drug excreted via the kidney, was investigated in patients on dialysis. Ten chronic hemodialysis patients with coexisting severe palpitation of supraventricular premature contractions (SVPC) were treated with 25 mg of pilsicainide hydrochloride before dialysis. All of their plasma concentrations were maintained within the therapeutic range and their mean dialysis rate was 32%. After 2 weeks, 7 patients were followed with consecutive daily dose treatment. In 3 of them, the dosage was returned to the single pre-dialysis administration because of the elevated plasma concentration reaching the toxic range 1 month after the start of administration. The dose schedule was maintained, and plasma pilsicainide concentrations remained within the therapeutic range during the 6-month follow-up. No abnormal findings were found in any parameters of electrocardiography, echocardiography or biochemistry. The number of SVPC diminished >90% compared to the pretreatment level.
Parathyroidectomy in Chronic Renal Failure: Short- and Long-Term Results on Parathyroid Function, Blood Pressure and Anemia
Authors: Coen G. , Calabria S. , Bellinghieri G. , Pecchini F. , Conte F. , Chiappini M.G. , Ferrannini M. , Lagona C. , Mallamace A. , Manni M. , DiLuca M. , Sardella D. , Taggi F.
Published: April 2003

To evaluate the long-term results of parathyroidectomy (PTX) on parathyroid function, blood pressure and anemia, data of 45 patients with secondary Hyperparathyroidism in dialysis who had undergone PTX were collected retrospectively from 8 different dialysis units. The patients, 25 M and 20 F, mean age 56 ± 11 years, who were followed up for an average period of 3.3 ± 2.3 years, were divided into four groups according to the surgical procedure: 19 patients had had a subtotal PTX; 10 patients had undergone total PTX with autotransplantation (AT); 10 patients had had total PTX without AT, and 6 patients had undergone partial PTX. Taking a reduction in intact PTH >50% as sign of successful PTX, only 5 patients did not attain this result. Considering values of PTH between 20 and 200 pg/ml at the mid-term observation (1–2 years) as the optimal result, values under 20 pg/ml as an expression of permanent hypoparathyroidism, and those above 200 pg/ml as indicating persistent/recurrent hyperparathyroidism, 65.5% of patients operated with subtotal PTX and total PTX + AT had a therapeutic success, versus 31.2% of patients in the other two groups, due to excess permanent hypoparathyroidism and persistent/recurrent hyperparathyroidism; 20 of 45 patients with preoperative hypertension experienced a statistically and clinically significant decrease in blood pressure levels. An increase in serum hemoglobin was also observed, despite a reduction of administered erythropoietin. In conclusion, the results of PTX obtained from this multicenter study are comparable to those reported by single leading centers. Recommended surgical procedures are subtotal PTX and total PTX with AT. The fall in blood pressure in hypertensive patients is clinically significant, and improvement in anemia is also observed with a reduction in erythropoietin dosage.
Increased Glomerular Cell Heparan Sulfates in vitro by Ciclosporin A: A Possible Explanation of Its Beneficial Effect in Idiopathic Nephrotic Syndrome
Authors: Birmelé Béatrice , De Agostini Ariane , Girardin Eric P.
Published: April 2003

Background/Aim: In idiopathic nephrotic syndrome (INS), ciclosporin A (CsA) was shown to decrease proteinuria, an effect explained by its immunologic and hemodynamic actions. In order to determine whether CsA could have a direct action on glomerular cells, we studied the effect of CsA on glomerular cells in vitro, particularly on glycosaminoglcycans (GAG) and heparan sulfates (HS) which are decreased in INS patients. Methods: Human glomerular epithelial cells and rat mesangial cells were cultured at various concentrations of CsA. HS were quantified using a cationic membrane after metabolic labeling. Results: Mesangial cell GAG and HS and epithelial cell HS increased significantly when cells were cultured with CsA. For both cell types this increase was prevailing on the secreted fraction of HS in comparison with the cellular fraction. CsA induced also an increase in cellular cAMP levels, but the effect of CsA was not transduced via a cAMP pathway. Conclusions: CsA is able to increase glomerular GAG and HS in vitro. As this effect of CsA was the opposite effect on glomerular cells to the effect of plasma from INS patients, we conclude that this direct action of CsA on glomerular cells could explain in part the effect of this drug in decreasing proteinuria in INS.
Apolipoprotein(a) Phenotype, Albumin Clearance, and Plasma Levels of Lipoprotein(a) in Peritoneal Dialysis
Authors: Iliescu Eduard A. , Marcovina Santica M. , Morton Alexander R. , Koschinsky Marlys L.
Published: April 2003

This cross-sectional study was undertaken to examine the relationship between plasma lipoprotein(a) [Lp(a)] level and peritoneal dialysis (PD) albumin clearance while controlling for the influence of the apolipoprotein(a) [apo(a)] phenotype. Plasma Lp(a) level, PD albumin clearance, and apo(a) phenotype (high vs. low molecular weight, HMW vs. LMW) were determined in 54 PD patients. Apo(a) phenotypes were 24 LMW and 30 HMW. The plasma Lp(a) level was high (>65 nmol/l) in 17 of 24 patients with LMW phenotype versus 2 of 30 with HMW phenotype (χ2, p < 0.01). Spearman correlation coefficients of Lp(a) with PD, urine, and total albumin clearances were –0.05 (p = 0.74), –0.04 (p = 0.80), and –0.09 (p = 0.51), respectively. The apo(a) isoform size was the only significant predictor of Lp(a) in multivariate analysis. In this study, there was no association between PD albumin clearance and Lp(a) level. The association between apo(a) phenotype and Lp(a) level is in keeping with studies in the general population. There is a strong genetic influence on Lp(a) level in PD patients.
Development of Porphyria cutanea tarda in a Hemodialysis Patient after Reactivation of Hepatitis C Virus Infection
Authors: Albalate Marta , Fariñas M. Carmen , Octavio Juan Gomez , Perez Jesús Hernández , Goicoechea Marian , Caramelo Carlos
Published: April 2003

Cases of porphyria cutanea tarda (PCT) are occasionally reported in hemodialysis patients. Recently, hepatitis C virus has been recognized as a precipitating factor of PCT. The activity of the liver disease may be critical for the appearance of PCT. In this regard, liver disease reactivation after treatment with interferon alpha (IFN-α) is a well-known phenomenon. We report the case of a hemodialysis patient who developed PCT coincidentally with reactivation of liver disease, immediately after treatment with IFN-α. Therefore, in the present case, reactivation of hepatitis after IFN-α withdrawal could be the triggering factor. The occurrence of a bout of PCT should be considered as a possible complication at the end of IFN-α therapy, if reactivation of the disease exists.
Nutritional Status and Amino Acids in Granulocytes and Plasma in Patients with Chronic Renal Disease and Varying Residual Renal Function
Authors: Ivarsen P. , Tietze I.N. , Pedersen E.B.
Published: April 2003

Background: Protein metabolism changes with loss of renal function resulting in deterioration of nutritional status. Whether changes in macroscopic (anthropometry and subjective global nutritional assessment (SGNA)) and cellular (plasma and granulocyte free amino acid concentration) nutritional status with loss of residual renal function are related is not known. Methods: Anthropometric variables, SGNA, and blood samples were measured after a night’s fast in 43 patients (age 57 years, median (range 27–77), 32 males and 11 females) with chronic renal disease. A 24-hour urine sample was collected the day before the study for calculation of creatinine clearance and protein nitrogen appearance rate. The patients were stratified according to creatinine clearance (group I: >35 ml/min/1.73 m2, group II 35–15 ml/min/1.73 m2, group III <15 ml/min/1.73 m2). Results: In males a significant lower body weight (p < 0.05) and upper mid-arm muscle area (p < 0.05) was found in group III compared to group I. SGNA indicated suboptimal nutritional status in 12 patients. In group I all had normal SGNA while in group II and group III, 26 and 57% respectively were malnourished. SGNA was significantly and negatively correlated to upper mid-arm muscle area (ρ = –0.37, p < 0.05) and percent body fat mass (ρ = –0.46, p < 0.01) and positively correlated to percent ideal body weight (ρ = 0.48, p < 0.01). Nine patients with malnutrition (M) were compared with 9 well-nourished (N) patients. They were comparable with respect to creatinine clearance (M: 13 ± 5 ml/min/1.73 m2; N: 16 ± 7 ml/min/1.73 m2), age and sex. In malnourished patients plasma concentration of nonessential amino acids was higher (23%, p < 0.05). The intracellular concentration was generally not affected except for sulfur amino acid methionine which was increased by a factor of 2.5 (p < 0.05) and taurine decreased by a factor of 1.6 (p < 0.05). Conclusion: Loss of renal residual function worsened both macroscopic and cellular nutritional status. SGNA correlated to objective measures of nutritional status and is clinically usable. In malnourished chronic renal patients, increased plasma concentration of nonessential amino acids was found which might indicate increased protein degradation.
Selective Hypoaldosteronism due to Combined Defects of the Conversion from Inactive Renin to Active Renin and the Aldosterone Biosynthesis from Corticosterone
Authors: Muto Shigeaki , Akai Youichi , Ono Shuichi , Kusano Eiji , Asano Yasushi
Published: April 2003

A 24-year-old Japanese woman with IgA nephropathy exhibited a decreased serum aldosterone level with normal plasma renin activity after toxemia of pregnancy. Our studies revealed selective hypoaldosteronism with normal adrenoglucocorticoid functions. Levels of serum corticosterone and deoxycorticosterone were normal. Resting plasma renin activity was normal, and plasma levels of total and inactive renin were increased. Rapid ACTH administration failed to stimulate any secretion of aldosterone, whereas it adequately increased serum cortisol, deoxycorticosterone, and corticosterone concentrations. Responses of both plasma renin activity and serum aldosterone level to the furosemide-posture challenge were blunted. Angiotensin II also failed to stimulate any secretion of aldosterone despite a progressive rise in blood pressure and an appropriate increase in serum corticosterone. These results suggest that combined defects of the conversion from inactive renin to active renin and aldosterone biosynthesis are the causes of selective hypoaldosteronism in our patient.
Effect of Dialysis Dose on Nutritional Status of Children on Chronic Hemodialysis
Authors: Marsenić Olivera , Peco-Antić Amira , Jovanović Olga
Published: April 2003

It had been suggested that larger hemodialysis (HD) doses in children could result in better appetite, higher protein intake, better nutritional status and better growth. We investigated how different HD doses affect protein intake and nutritional status of children on chronic HD. Indices of nutritional status used were normalized protein catabolic rate (nPCR) calculated by formal 3-sample urea kinetic modeling and serum albumin level. Data of 38 HD sessions in 15 stable patients (6 males, 9 females) aged 14.5 ± 3.28 years (mean ± SD) were analyzed. HD sessions were divided into three groups based on delivered Kt/V: group 1 (n = 5), inadequate (Kt/V < 1.3, mean 1.05 ± 0.14); group 2 (n = 12), adequate (Kt/V = 1.3–1.6, mean 1.50 ± 0.07) and group 3 (n = 21), high (Kt/V >1.6, mean 1.94 ± 0.22). Mean nPCR and Kt/V per patient during the studied week were estimated for 11 patients in whom 3 HD sessions were available within the 38 sessions analyzed. Serum albumin level was adequate in all patients (43.77 ± 2.28 g/l). Mean overall Kt/V and nPCR were 1.68 ± 0.36 and 1.26 ± 0.23, respectively, r = 0.430. Average nPCR differed between groups depending on Kt/V. It was lowest in group 1 (1.01 ± 0.12 g/kg/day) where the highest correlation between nPCR and Kt/V was found (r = 0.648). nPCR was higher and similar in groups 2 (1.27 ± 0.23 g/kg/day) and 3 (1.31 ± 0.22 g/kg/day), with low correlation coefficients between nPCR and Kt/V in both groups (r = 0.275 and r = 0.197, respectively). A weak positive correlation (r = 0.249) between nPCR and Kt/V was found when average weekly values per patient (n = 11) were analyzed. Results of groups 1 and 2 confirm, what is already well established in adults, that adequate dialysis needs to be achieved in order to insure good protein intake. However, our data clearly show that nPCR did not increase with a further increase in delivered HD dose, i.e. Kt/V >1.6. Our results show that the nutritional status of children on chronic HD does not seem to benefit from very high HD doses (Kt/V >1.6).
Dialysis in Non-Renal Organ (Liver) Transplantation
Authors: Richardson Donald
Published: April 2003

The renal management of acute hepatic failure and liver transplantation requires an understanding of the features of liver failure and the causes of liver graft dysfunction. The management of any underlying pathology in addition to supportive care is fundamental to successful management and a return to independent renal function. These issues are discussed particularly in relationship to a case history involving a patient presenting with acute fulminant liver failure secondary to a paracetamol overdose who was successfully treated by liver transplantation and continuous veno-venous haemodiafiltration. The liver can be successfully transplanted but acute renal failure is a severe complication post-transplantation. Its appearance can be predicted in patients with pre-transplant renal dysfunction, severe graft dysfunction, or both. It may be avoided through careful selection of transplant recipients and correct timing of transplantation. Prevention of renal failure, appropriate patient selection for transplantation and timely procurement of a donor organ are vital for best use of limited donor resources. Treatment success depends on patient and donor selection, skilled surgeons, careful post-operative care, and successful immunosuppression.
Renal Localisation of Rat Cysteine Dioxygenase
Authors: Parsons Richard B. , Sampson David , Huggins Cerys C. , Waring Rosemary H. , Williams Adrian C. , Ramsden David B.
Published: April 2003

Background/Aims: Cysteine dioxygenase (CDO, EC 1.13.11.20) catalyses the conversion of cysteine to cysteine sulphinic acid and controls the rate-limiting step of sulphate production. Many neurological and non-neurological diseases are associated with abnormalities in CDO activity, giving rise to reduced availability of sulphate. The importance of the kidney in the sulphation of xenobiotics has long been recognised, but little is known about the renal expression of key enzymes in this pathway. In order to address this, this report demonstrates the expression of CDO in the kidney. Methods: Two previously characterised antibodies were used to investigate the localisation and expression of CDO using immunohistochemistry, in-situ hybridisation and Western blotting. Results: Renal CDO was shown to exist as a 68-kDa protein, which was unaffected by levels of cysteine and methionine that had been previously shown to induce hepatic CDO. CDO protein expression was present in the proximal convoluted tubules of the cortex and the collecting ducts of both the medulla and papilla. Discussion: These results suggest that renal CDO is immunologically identical to that of the liver. Its expression in the kidney tubules, the major site of sulphation in the kidney, suggests that CDO in the kidney may play a role in both xenobiotic metabolism and sodium and water homeostasis.
The Insulin-Like Growth Factor System in Kidney Diseases
Authors: Richmond E.J. , Uzri A. , Rogol A.D.
Published: April 2003

The insulin-like growth factor system is intimately involved in renal development, growth, function and the pathophysiology of several disease states. Exogenous IGF-I increases GFR and RPF, perhaps mediated by nitric oxide (NO). In chronic renal failure, IGF-I, the binding proteins and their fragments decrease bioavailability. After transplantation, the levels of bioactive IGF-I increase likely due to better nutrition and increased clearance of the binding proteins and their fragments. In the nephritic syndrome, a similar mechanism may be active, in that the binding proteins and their fragments may inhibit IGF-I action.
Nephrotic Origin Hyperlipidemia, Relative Reduction of Vitamin E Level and Subsequent Oxidative Stress May Promote Atherosclerosis
Authors: Skrzep-Poloczek Bronisława , Tomasik Andrzej , Tarnawski Roman , Hyla-Klekot Lidia , Dyduch Antoni , Wojciechowska Celina , Wesołowski Wiesław , Kopieczna-Grzebieniak Ewa , Zalejska-Fiolka Jolanta , Widera Ewa
Published: April 2003

Background: The relation between nephrotic syndrome and atherosclerosis has not yet been fully clarified, although the high levels of low-density lipoprotein cholesterol usually found in this syndrome may give rise to atherosclerosis. This study was intended to test the disturbances of antioxidant/oxidant status in children with nephrotic syndrome (NS). Methods: 8 children in the active stage (AS) of NS , 7 children during the remission stage (REM) of NS, and 14 control subjects (CTRL) were enrolled into the study. The levels of plasma total cholesterol (TC), HDL-cholesterol (HDL-chol), LDL-cholesterol (LDL-chol), triglycerides (TG), vitamin E and 7-ketocholesterol (7KCH) before and after plasma saponification were measured. Results: A significant increase in the concentrations of TC, LDL-chol, vitamin E and total 7KCH in AS patients have been found. These patients had also a lower vitamin E/LDL-chol ratio. These changes have not been observed in the remission stage of nephrotic syndrome. Higher amounts of electronegatively charged-(oxidized) LDL particles as well as different oxysterols in AS patients have also been demonstrated. Conclusion: The study revealed significant disturbances in oxidant status during NS leading to plasma accumulation of oxidized LDL and cholesterol oxidation products that exert cytotoxicity and are known to induce atherosclerosis. We suggest that this may constitute an important link between nephrotic syndrome and atherosclerosis.
CD31 Expression on Leukocytes Is Downregulated in vivo during Hemodialysis
Authors: Kawabata Kenji , Nakai Shigeru , Miwa Masamiki , Sugiura Tatsuki , Otsuka Yuka , Shinzato Toru , Hiki Noriyuki , Tomimatsu Ikuko , Ushida Yumi , Hosono Fumiko , Maeda Kenji
Published: April 2003

Background/Aim: CD31 on leukocytes is the adhesion molecule involved in the leukocyte extravasation in inflammatory conditions. During hemodialysis with cellulosic membranes, it is considered that activated leukocytes adhere to endothelium, but do not show extravasation. However, it is not elucidated why activated leukocytes do not show endothelial transmigration during hemodialysis with cellulosic membranes. Methods: In the present study, changes in the expressions of Mac-1 and CD31 on granulocytes and monocytes were analyzed by flow cytometry during hemodialysis in 7 patients treated with regenerated-cellulose (RC) membranes and next with polysulfone (PS) membranes. Results: During dialysis with RC, Mac-1 expressions on granulocytes and monocytes both significantly increased as compared with predialysis values and across the dialyzer. During dialysis with RC, the CD31 expression on granulocytes and monocytes significantly decreased as compared with predialysis values. During dialysis with PS, changes in Mac-1 and CD31 expressions on granulocytes and monocytes were smaller than those during dialysis with RC. Conclusions: Decreased CD31 expression on leukocytes may affect leukocyte function more in patients chronically hemodialyzed with RC than in those hemodialyzed with PS, since CD31 is important in leukocyte transendothelial migration in inflammatory conditions.
Tissue-Specific Induction of E-Selectin in Glomeruli Is Augmented following Diabetes mellitus
Authors: Narumi Shosaku , Onozato Maristela L. , Tojo Akihiro , Sakamoto Shinji , Tamatani Takuya
Published: April 2003

We recently demonstrated that induction of adhesion molecules is tissue, cell type, and blood vessel size specific. We examined here whether the glomeruli, a peculiar vascular system, express adhesion molecules in a specific manner in the murine kidney. In addition, since serum levels of soluble adhesion molecules have been reported to be elevated in diabetic patients, we examined the influence of diabetes mellitus on the induction of adhesion molecules in the kidney. Analysis of E-selectin mRNA expression by in situ hybridization indicated that it was selectively induced in glomeruli by intravenous administration of interleukin-1β, while ICAM-1 mRNA expression was seen diffusely in endothelium lining the small arteries and capillaries or in glomeruli, and VCAM-1 mRNA expression was most prominent in endothelial cells of larger blood vessels. Induction of E-selectin mRNA expression in glomeruli by proinflammatory stimuli was augmented in streptozotocin-induced diabetic mice as compared with control mice, while ICAM-1 or VCAM-1 mRNA induction was only slightly influenced. Furthermore, immunohistochemical analysis showed that selective expression of E-selectin in glomeruli was augmented predominantly in epithelial cells, depending on the duration of diabetes mellitus, in KK-Ay mice. These findings suggest that glomerulus-specific expression of E-selectin is related to the development of diabetic nephropathy.
Mizoribine Ameliorates the Tubulointerstitial Fibrosis of Obstructive Nephropathy
Authors: Sato Norihiro , Shiraiwa Kazumi , Kai Kiyonori , Watanabe Atsushi , Ogawa Shinichi , Kobayashi Yoshiro , Yamagishi-Imai Hiroko , Utsunomiya Yasunori , Mitarai Tetsuya
Published: April 2003

Mizoribine has been shown to possess an immunosuppressive action that inhibits the proliferation of lymphocytes selectively by interfering with inosine monophosphate dehydrogenase. Recent studies have demonstrated that mizoribine improves renal tubulointerstitial fibrosis in the rat model of unilateral ureteral obstruction (UUO) by inhibiting the infiltration of macrophages. We, therefore, examined the dose dependency of the suppressive effect of mizoribine on the infiltration of interstitial macrophages and T lymphocytes and the interstitial volume in UUO-treated kidneys. Furthermore, we investigated the expression of osteopontin (OPN), known to be a chemoattractant protein for macrophages, in the renal cortex. In rats with UUO, the interstitial volume was markedly expanded, and macrophage and T lymphocyte infiltration in the interstitium and the expression of OPN in the cortical tubules were greatly increased. Treatment with mizoribine ameliorated the increase in interstitial volume induced by UUO. Interstitial infiltration of macrophages and T lymphocytes was dose dependently suppressed by mizoribine, and the decreased macrophage infiltration was correlated with inhibition of tubular OPN expression. These results suggest that mizoribine has a beneficial effect on several steps contributing to the progression of tubulointerstitial fibrosis caused by obstruction of the ureter.
Role of Adhesion Molecules in Mononuclear Cell Apoptosis Induced by Cuprophan Hemodialysis Membranes
Authors: Carracedo Julia , Ramírez Rafael , Martín-Malo Alejandro , Rodríguez Mariano , Madueño Juan A. , Aljama Pedro
Published: April 2003

Background/Aim: Hemodialysis with Cuprophan (CU) membranes induces mononuclear cell activation, leading to increased expression of adhesion molecules, formation of cell aggregates, and apoptosis. It is likely that structure(s) of the CU membrane interact with mononuclear cell surface molecules which transduce biochemical signals to the cell. Interactions between adhesion molecules and extracellular matrix have been implicated in cell activation, proliferation, and/or apoptosis. In the present work, we study whether adhesion molecules may be involved in CU-induced mononuclear cell aggregation and/or apoptosis. Methods: The present study was performed using THP-1 cells, a human monocytic cell line, cultured in the presence of the CU membrane. CD11b and CD54 expression was studied with fluorescent monoclonal antibodies. Cell aggregation was quantified using a phase-contrast microscope. Apoptosis was evaluated by either light microscopy or annexin V labeling. Results: The results show that incubation of CU membranes with the proteins CD11b, CD18, and CD54 or the blockade of these cell surface molecules with specific monoclonal antibodies inhibited the CU-induced aggregation and apoptosis in a dose-dependent manner. Conclusion: These results suggest that CU membranes interact selectively with these specific proteins to induce cell activation which ultimately results in apoptosis.
Kidney Ischaemia-Reperfusion Injury and Polyribosome Structure
Authors: Pleština Stjepko , Gamulin Stjepan
Published: April 2003

Background: Inhibition of protein synthesis and polyribosome disaggregation are the early events in cell injury provoked by various pathogenic mechanisms, including energy depletion. Polyribosome disaggregation might be expected to occur during ischaemia-reperfusion injury due to ischaemic energy depletion, but also due to detrimental effects of reactive oxygen species on various macromolecules and cellular structures. Methods: Mouse kidney ischaemia-reperfusion injury was provoked by temporary clamping of the renal artery. The polyribosome sedimentation pattern was analyzed by sucrose density centrifugation of kidney postmitochondrial supernatant. Results and Conclusions: Ischaemia for 5 min in the mouse kidney provoked polyribosome disaggregation and an increase of monomer ribosome fraction which was augmented during 10–360 min of reperfusion. Recovery of polyribosome aggregates appeared between 6 and 24 h of reperfusion. Cycloheximide pretreatment prevented only polyribosome disaggregation caused by ischaemia and not that caused by reperfusion. This indicates different mechanisms of polyribosome disaggregation during ischaemia and reperfusion. It probably occurs in the former due to inhibition of initiation of translation, resulting in accumulation of unprogrammed monomer ribosomes, and in the latter due to the splitting of mRNA and breakdown of polyribosomes. Reperfusion did not increase ribonuclease activity in kidney cytosol, but increased the tissue concentration of malonaldehyde, indicating an augmentation in oxygen free radical generation. Possibly these may have caused a non-enzymatic breakdown of polyribosomes. However, pretreatment with allopurinol did not prevent polyribosome breakdown during ischaemia-reperfusion injury.
Identification of T Helper Cell Subsets in Continuous Ambulatory Peritoneal Dialysis Patients
Authors: Yokoyama Takashi , Nitta Kosaku , Futatsuyama Kazuya , Hayashi Tetsuo , Honda Kazuho , Uchida Keiko , Kawashima Akira , Yumura Wako , Nihei Hiroshi
Published: April 2003

Background/Aim: End-stage renal failure induces a clinical state of immunodeficiency with a higher incidence of infections and a higher mortality due to infectious complications as compared with the normal population. A crucial element in this immune response is the development of a network of cytokines. CD4-positive T helper (Th) cells differentiate into either Th1 or Th2 cells in response to various stimuli. It is important to examine whether the impaired immune responses in patients with end-stage renal disease are due to an enhanced Th1 response or a reduced number of Th2 cells. Method: Using a newly developed immunofluorescence staining of intracellular cytokines for flow cytometric analysis, we studied Th subsets in 24 patients on continuous ambulatory peritoneal dialysis (CAPD). Results: The proportions of Th1 cells did not differ between CAPD patients (18.7 ± 1.8%) and controls (19.6 ± 1.5%). Unlike Th1 cells, a significantly higher proportion of CD4 cells in CAPD patients is characterized by a Th2-type cytokine secretion pattern as compared with healthy controls: 2.9 ± 0.8% versus 1.7 ± 0.4%. Conclusion: These data demonstrate that Th cells from CAPD patients manifest a dysregulated differentiation profile characterized by a major increase in the percentage of Th2 cells and by a normal percentage of Th1 cells.
Endothelial Nitric Oxide Synthase Intron 4 Polymorphism Influences the Progression of Renal Disease
Authors: Asakimori Yukiteru , Yorioka Noriaki , Yamamoto Ichiro , Okumoto Satoshi , Doi Shigehiro , Hirai Takayuki , Taniguchi Yoshihiko
Published: April 2003

Background/Aim: Nitric oxide is a potent regulator of intrarenal hemodynamics and may influence the renal function. We investigated whether polymorphism of intron 4 of the endothelial constitutive nitric oxide synthase (ecNOS) gene is related to the progression of chronic renal failure. Methods: Polymorphism of ecNOS intron 4 was studied in 1,005 hemodialysis patients (710 with nondiabetic nephropathy and 295 with diabetic nephropathy) and was compared with the findings in 189 healthy subjects. ecNOS genotypes were determined by the polymerase chain reaction, followed by agarose gel electrophoresis. Results: The frequencies of ecNOS4a/a, ecNOS4a/b, and ecNOS4b/b genotypes were, respectively, 0% (0/189), 13.8% (26/189), and 86.2% (163/189) in the control group; 1.7% (12/710), 22.1% (157/710), and 76.2% (541/710) in the nondiabetic nephropathy group, and 1.0% (3/295), 22.7% (67/295), and 76.3% (225/295) in the diabetic nephropathy group. The frequency of ecNOS4a (ecNOSa/a and ecNOSa/b) was significantly higher in both the nondiabetic group and in the diabetic group than in the controls (p = 0.0025 and p = 0.0438, respectively). Conclusion: There was a significantly higher frequency of the a allele of intron 4 in both nondiabetic and diabetic hemodialysis patients, so the polymorphism of intron 4 of the ecNOS gene may have a wide influence on the progression of renal disease.
Vitamin D Receptor Gene Polymorphism Detected by Digestion with Apa I Influences the Parathyroid Response to Extracellular Calcium in Japanese Chronic Dialysis Patients
Authors: Yokoyama Keitaro , Shigematsu Takashi , Kagami Sino , Tsukada Toshihiko , Arai Tomoko , Hara Sigeko , Yamada Akira , Kawaguchi Yoshindo , Hosoya Tatsuo
Published: April 2003

Background: To play its physiological role, 1,25(OH)2D3 must bind to a specific vitamin D receptor (VDR) in the nucleus. We have previously reported that VDR gene polymorphism influences the parathyroid function in patients with end-stage renal disease (ESRD). In the present study, we have investigated the relationship between the parathyroid responsiveness and VDR gene polymorphism, as detected by the Apa I restriction enzyme, by changing the concentration of Ca2+ in the dialysate. Methods: 58 Japanese ESRD patients undergoing renal replacement therapy in our institution were evaluated. Genomic DNA was extracted from peripheral leukocytes and digested at the intron between exon 8 and exon 9 of the VDR gene using Apa I enzyme. Then alleles were classified into genotype A (undigested allele) and genotype a (digested allele). Extracellular ionized calcium ([Ca2+]e), serum phosphate, and intact parathyroid hormone (PTH) were measured before and after each hemodialysis (HD) session with dialysates having different concentrations of Ca2+ (1.5 or 1.25 mmol/l). The significance of differences in statistical analyses was defined within confidence limits of 5.0%. Results: The AA, Aa, and aa genotypes were observed in 7/58 patients (12.1%), 23/58 patients (39.6%), and 28/58 patients (48.3%), respectively. The PTH reduction after HD with the 1.5-mmol/l Ca dialysate did not differ significantly between group AA+Aa and group aa. On the other hand, the PTH increase was significantly higher in group aa than in group AA+Aa after HD with the 1.25-mmol/l Ca dialysate (p = 0.0107), despite a similar PTH level before HD. Similarly, the percent increase of PTH after HD with the 1.25-mmol/l Ca dialysate was significantly higher (p = 0.0112) in group aa (50.2 ± 9.4%) than in group AA+Aa (19.7 ± 7.2%). There were no significant differences between the two groups in [Ca2+]e nor in serum phosphorus (Pi) before and after HD with either dialysate. Group AA+Aa and group aa did not show statistically significant differences in age, female/male ratio, ratio of diabetic nephropathy, or dialysis period. Conclusions: The study results showed that the patients in group aa were more sensitive to changes in [Ca2+]e than those in group AA+Aa. Moreover, they suggested that the VDR gene polymorphism may affect parathyroid responsiveness to changes in [Ca2+]e, which in turn may influence onset and progression of hyperparathyroidism in ESRD patients.
Renal Mineral Handling in Normal Rats Treated with Sevelamer Hydrochloride (Renagel®), a Noncalcemic Phosphate Binder
Authors: Nagano Nobuo , Miyata Sonoe , Obana Sachiko , Eto Nobuaki , Fukushima Naoshi , Burke Steven K. , Wada Michihito
Published: April 2003

The effects of sevelamer hydrochloride (Renagel®; hereafter referred to as sevelamer), a noncalcemic phosphate binder, on renal mineral handling were examined in rats. Normal rats were fed a diet containing 0.3, 1, 3, and 5% sevelamer for 8 days, and serum, urine, and the immunohistochemical localization of the type II Na/Pi cotransporter protein in the kidney were analyzed. Rats treated with 3 or 5% sevelamer showed significant decreases in serum phosphorus (P) and parathyroid hormone (PTH) levels, with no changes in serum calcium (Ca), magnesium (Mg), or 1,25(OH)2D3 levels. Increases were observed in urinary excretions of Ca and Mg associated with a reduction in the PTH level in rats treated with 3 or 5% sevelamer. Rats treated with 1% or higher concentrations of sevelamer showed significant dose-dependent and marked reductions of the urinary P excretion, and the tubular reabsorption of P was maximized to almost 100% in the 5% sevelamer group. The hypophosphaturia in rats treated with 3 or 5% sevelamer was accounted for by the reductions in serum PTH and P per se, and immunohistochemical analysis showed that the expression of type II Na/Pi cotransporter protein was markedly increased at the brush border membranes of the deep and superficial nephrons in rats treated with 5% sevelamer as compared with rats given a normal diet. In conclusion, sevelamer rapidly lowered serum P and PTH levels in normal rats. Sevelamer treatment also produced a marked hypophosphaturia associated with translocation of type II Na/Pi cotransporter protein and increased urinary Ca and Mg excretions by the reduction of PTH.
The Low and High Frequency Auditory Steady State Responses Mature at Different Rates
Authors: Savio G. , Cárdenas J. , Pérez Abalo M. , González A. , Valdés J.
Published: April 2003

The age-related changes in the fast rate (70–110 Hz) auditory steady state response elicited by multiple-frequency tones (MSSR) that were amplitude-modulated (AM) are reported here. The MSSR was recorded in a sample of 64 well babies distributed into three age groups: 0–29 days (n = 25); 1–6 months (n = 26); 7–12 months (n = 13). Four simultaneously presented AM tones (0.5, 1, 2 and 4 kHz) were delivered monaurally through TDH 49 earphones, at different intensities (between 90 and 30 dB SPL). Clear developmental changes were found between birth and 12 months of age in response threshold, amplitude and detectability. Statistical analysis revealed that these changes occurred at different rates for low- and high- frequency responses. Nonetheless adult-like hearing thresholds were estimated reasonably well in most newborns and well babies, for all frequencies tested. Therefore the MSSR technique could be useful for objective frequency-specific audiometry beginning at birth.
Oxidant Mechanisms in Neonatal Hypoxia-Ischemia
Authors: Ferriero Donna M.
Published: April 2003

The neonatal brain appears to be selectively vulnerable to oxidative stress. Several potential mechanisms associated with altered reactive oxygen species metabolism would explain the increased susceptibility. They include increased accumulation of hydrogen peroxide with subsequent neurotoxicity. This enhanced neurotoxicity from H2O2 accumulation may be related to inadequate scavenging abilities of the immature nervous system, such as lower glutathione peroxidase activity. Contributing to the immaturity of the scavenging enzymes is the inability of the developing nervous system to maintain glutathione stores. The immature nervous system is rich in iron, and has more free iron than the mature nervous system. As H2O2 accumulates because of these improper defense mechanisms, it is exposed to this free iron. This exposure results in the generation of OH radical (Fenton reaction), a more potent free radical that can cause severe damage. The rapid conversion of H2O2 to OH in the setting of free iron sets up the immature nervous system for increased cytotoxicity. Understanding the molecular mechanisms of oxidative stress will lead to better therapies for neonatal hypoxia-ischemia.
The STRO-1+ Marrow Cell Population Is Multipotential
Authors: Dennis James E. , Carbillet Jean-Pierre , Caplan Arnold I. , Charbord Pierre
Published: April 2003

Human marrow-derived STRO-1+ cells were tested for their ability to differentiate into multiple mesenchymal phenotypes. STRO-1+ cells were isolated from long-term cultures of human marrow cells by magnetic immunobeads linked to the antibody STRO-1. Stromal layers generated from STRO-1+ cells, when cocultured without exogenous cytokines for several weeks with CD34+/CD38+ and CD34+/CD38low cells, were able to induce a 10- to 20-fold increase in colony-forming units, and to sustain cobblestone area colony-forming cells with a distinct time course for the different hematopoietic precursors. A myofibroblastic and adipocytic phenotype was observed in hematopoiesis-supportive stromal cells, as shown by electron microscopy and staining of lipids with Nile red. The adipocytic potential of STRO-1+ cells was further demonstrated by flow cytometry of Nile red O-stained cells cultured in adipocyte-induced medium. The same population of STRO-1+ cells cultured in osteoblast-inducing medium was shown to have osteogenic potential, as demonstrated in vitro by the formation of mineral (von Kossa staining), and in vivo by the formation of bone tissue within porous calcium phosphate ceramics implanted into athymic mice. This population of STRO-1+ cells was also shown to have chondrogenic potential in aggregate cultures which displayed a morphologic appearance of cartilage and stained positively with antibodies specific to type II and type X collagens. These results show that the subset of marrow cells that express the STRO-1 antigen is capable of differentiating into multiple mesenchymal lineages including hematopoiesis-supportive stromal cells with a vascular smooth muscle-like phenotype, adipocytes, osteoblasts and chondrocytes.
Energy-Dependent Types of Cell Death in MCF-7 Breast Cancer Cell Tumors Implanted into Nude Mice
Authors: Formigli Lucia , Zecchi Orlandini Sandra , Capaccioli Sergio , Poupon Marie-France , Bani Daniele
Published: April 2003

The present study aims at verifying whether aponecrosis, a novel type of cell demise sharing the features of both apoptosis and necrosis previously identified in in vitro experiments, could represent a natural phenomenon that also occurs in vivo. The pathways of cell death were analyzed morphologically in MCF-7 breast cancer cell tumors implanted into nude mice. These tumors grew as encapsulated masses devoid of blood vessels, thus allowing for the creation of a gradient of oxygen and nutrients from the periphery inwards. Expression of wild-type p53 and DNA fragmentation were investigated as apoptotic markers. Further experiments were carried out on MCF-7 cells cultured in vitro in the presence and absence of oxygen and nutrients. In these cultures, the intracellular ATP levels were measured and related to the types of cell death recognized morphologically. Apoptotic cells were observed in the outer portion of the MCF-7 cell tumors close to blood vessels. In the inner portion of the tumors which lacks blood supply, several cells simultaneously showed signs of both apoptosis and necrosis, being identifiable as aponecrotic cells. Similarly, aponecrotic cells were also observed in the starved cultures, in concomitance with intracellular ATP depletion. These findings suggest that MCF-7 cells may accomplish the apoptotic process only when sufficient oxygen and energy supply are available. As the energy level decreases, aponecrosis may ensue as the result of an incomplete execution of the apoptotic program.
In vivo Mechanical Properties of Proximal and Distal Aponeuroses in Human Tibialis Anterior Muscle
Authors: Muramatsu Tadashi , Muraoka Tetsuro , Takeshita Daisuke , Kawakami Yasuo , Fukunaga Tetsuo
Published: April 2003

Load-strain characteristics of distal (deep) and proximal (superficial) aponeuroses were determined in vivo for human tibialis anterior muscle (TA). Seven male subjects exerted isometric dorsiflexion torque from relaxation to voluntary maximum while elongation of both aponeuroses of TA was determined by ultrasonography. Two positions (end of the muscle belly and a proximal part) and one position (distal part) were scanned for the deep and superficial aponeuroses, respectively, and tendinous movements of the respective positions were determined. Based on the tendinous movements, elongation of each aponeurosis was determined. Both aponeuroses were elongated significantly, and there was no significant difference in strain between the deep (3.3 ± 0.8%) and superficial (3.0 ± 0.5%) aponeuroses. In addition, there was a significant linear relationship between strain of deep and superficial aponeuroses. It was suggested that both aponeuroses similarly act as an elastic component in pennate muscles.
Calcitriol per os Once, Twice or Three Times a Week: Effect of Different Schedules of Administration in Hemodialysis Patients
Authors: Manni Micaela , Calabria Santo , Dinnella Angela , D’Anello Emanuela , Mantella Daniela , Sardella Daniela , Sturniolo Antonio , Splendiani Giorgio , Coen Giorgio
Published: April 2003

Administration of a single dose of 1,25-OH2D3 can lower PTH levels for up to 4 days in chronic hemodialysis patients. Our purpose was to verify the effects of the same weekly dose of calcitriol per os given in one, two or three administrations, to patients on dialysis with secondary hyperparathyroidism. Thirty patients were studied, divided in to three groups each of 10 patients. Calcitriol therapy in group A was given as a single weekly dose of 0.08 µg/kg b.w. In group B the same total weekly dose was divided in two equal doses. In group C the same total weekly dose was divided in three times. Treatment lastet 2 months. After 8 weeks of therapy the fall in intact PTH was statistically significant in each group, respectively with one-way ANOVA: p < 0.02 (A); p < 0.002 (B); p < 0.001 (c). Two-way ANOVA for comparison of PTH % variation among the three groups was statistically significant p < 0.003. Significance was due to difference between group A and groups B and C. The present study confirms the efficacy of single dose in suppressing significantly intact PTH. However, when the same weekly dose is divided into two or in three time-spaced administrations, the suppressive effects are definitely increased.
Cytomegalovirus Colitis during Mycophenolate Mofetil Therapy for Wegener’s Granulomatosis
Authors: Woywodt Alexander , Choi Mira , Schneider Wolfgang , Kettritz Ralph , Göbel Ursula
Published: April 2003

Cytomegalovirus (CMV) infection of the gastrointestinal tract is an increasingly recognized cause of morbidity and mortality during the course of HIV infection and in association with immunosuppressive pharmacotherapy. Mycophenolate mofetil, a novel immunosuppressive drug, is currently used in renal transplant recipients and is under evaluation for a variety of disorders. There is preliminary evidence to suggest that CMV reactivation may be more common during treatment with mycophenolate than with other immunosuppressive drugs. We present the case of a 59-year-old male with Wegener’s granulomatosis who received mycophenolate and presented with guaiac-positive diarrhea 8 weeks after recovery from Salmonella brandenburg infection. CMV serology and assays for CMV antigens were entirely negative. Colonoscopy demonstrated pancolitis and examination of the specimens disclosed CMV infection. Ganciclovir was administered and the patient made an uneventful recovery. We discuss aspects of gastrointestinal CMV infection with an emphasis on pitfalls in diagnosis and the association with mycophenolate mofetil treatment. We also speculate as to the potential role of previous Salmonella infection and proinflammatory cytokines in CMV reactivation. In summary, when using mycophenolate, clinicians should be more aware of CMV reactivation and disease.
Alloimmune Hemolysis after Renal Transplantation
Authors: Li Fu Keung , Chan Tak Mao , Lai Ka Neng
Published: April 2003

A 35-year-old patient with blood group AB developed hemolysis 1 week after receiving a blood group B cadaveric kidney transplant. The patient’s serum was shown to contain anti-A antibody, which was likely to have been derived from passenger lymphocytes transplanted concurrently with the graft. The alloimmune hemolysis subsided spontaneously without treatment. The present case underscores the potential complication of ABO blood group-compatible but nonidentical organ transplantation. Clinical vigilance is important to differentiate from other more sinister causes of posttransplant hemolysis.
Concurrent Thrombosis of Cerebral and Femoral Arteries in a Patient with Nephrotic Syndrome
Authors: Lee Chien-Hung , Chen Kuo-Su , Tsai Feng-Chun , Chien Yu-Yi , Lee Ning
Published: April 2003

Although venous thrombosis is a frequently encountered problem in nephrotic syndrome, the occurrence of arterial thrombosis is much less common, and is usually associated with a poor prognosis. To the best of our knowledge, there has been only one reported case of concurrent cerebral and femoral artery thrombosis, that of a 23-year-old male who finally died. Herein, we report a case of a 35-year-old woman with nephrotic syndrome. She developed cerebral and femoral arterial thrombosis simultaneously when the nephrotic syndrome relapsed. Immediate thrombectomy of the femoral artery, followed by anticoagulation and immunosuppressive therapy, were employed. The patient recovered completely and is now doing well. Our experience indicates that multiple artery thrombosis in nephrotic patients may not necessarily carry a poor outcome if early and aggressive treatment can be undertaken.