bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Protein Meals on the Urinary Excretion of Various Plasma Proteins in Healthy Subjects
Authors: Narita Takuma , Kitazato Hiroji , Koshimura Jun , Suzuki Katsunori , Murata Masahiko , Ito Seiki 
Published: April 2003

To examine whether hemodynamic changes in response to acute protein loadings with different protein sources cause increases in urinary excretion of plasma proteins in healthy subjects, urinary excretions of various plasma proteins with various molecular radii and isoelectric points, namely albumin (Alb), IgG, IgG4, ceruloplasmin (CRL), and α<sub>2</sub>-macroglobulin (A2), were measured in healthy subjects after ingestion of a beef meal or of a tuna fish meal. Significant increases in urinary excretions of the negatively charged IgG4 and CRL and of the neutrally charged IgG were found in parallel with enhanced creatinine clearances after each protein ingestion. These renal responses returned to basal levels 9 h after the test. This finding suggests that in healthy subjects, the increase in glomerular filtration rate after acute protein loading caused selective enhancement of urinary excretions of plasma proteins with a molecular radius of approximately 55 Å (the radius of IgG, IgG4, and CRL), irrespective of the charge barrier of the glomerulus. The increases in these three plasma proteins may be induced by leakage via the shunt pathway in the glomerulus, as proposed earlier (see text). In contrast, increases in urinary excretions of A2 and Alb were not found. The former finding may be explained by the possibility that A2 would not pass through this pathway, since the molecular radius of A2 (88 Å) is larger than that of IgG, although the latter finding may be partially explained by preferential renal tubular reabsorption of Alb.
The Outer Membrane Protein I of <i>Pseudomonas aeruginosa </i>PAO1, a Possible Pollutant of Dialysate in Hemodialysis, Induces Cytokines in Mouse Bone Marrow Cells
Authors: Ino Mitsuhiro , Nagase Sohji , Nagasawa Toshiro , Koyama Akio , Tachibana Shinro 
Published: April 2003

The finding of outer membrane protein I (OprI) of <i>Pseudomonas aeruginosa</i> in hemodialyzers used by patients with end-stage renal failure led us to study the possible role of OprI as cytokine inducer. However, there are few reports on the biological activity of OprI, because it is difficult to obtain highly purified OprI. In this study, we attempt to establish a procedure for the efficient purification of OprI, which does not include lipopolysaccharide, from the bacterial culture broth, not hemodialyzers, to demonstrate that OprI is a potent cytokine inducer. From bacterial culture broth (1 liter), <i>P. aeruginosa</i> PAO1, which was confirmed previously by the sequence coding, was separated by centrifugation, high-performance liquid chromatography, and disk electrophoresis. Mouse bone marrow cells were stimulated by purified OprI, and the supernatants of the culture were analyzed by several enzyme-linked immunosorbent assay kits. The tumor necrosis factor alpha production stimulated by purified OprI was confirmed and degraded within 24 h. Furthermore, interleukin (IL) 1α, IL-1β, IL-6, and granulocyte-macrophage colony-stimulating factor were also induced by OprI despite the absence of lipopolysaccharide. We conclude that OprI has the potential to induce tumor necrosis factor alpha production in mouse bone marrow cells and that tumor necrosis factor alpha contributes to the induction of inflammatory cytokines, namely IL-1α, IL-1β, IL-6, and granulocyte/macrophage colony-stimulating factor, while lipopolysaccharide has little effect on these cells. These results suggest the presence of a pathway of inflammatory signal transduction triggered by OprI. In addition, OprI is possibly one of the harmful dialysate pollutants in hemodialysis patients besides the well-known lipopolysaccharide.
Risk Factors for Chronic Renal Dysfunction in Cardiac Allograft Recipients
Authors: Esposito C. , Semeraro L. , Bellotti N. , Fasoli G. , Fornoni A. , Rampino T. , Klersy C. , Campana C. , Gavazzi A. , Viganò M. , Dal Canton A. 
Published: April 2003

Renal dysfunction is one of the most common and threatening complications in heart transplant recipients. Even if ciclosporin seems to play a central role in inducing renal damage, other factors may concur or predispose to renal injury. In order to identify factors responsible for renal dysfunction, we retrospectively studied a cohort of 114 cardiac transplant recipients during a follow-up period of at least 3 years. The patients had a normal renal function before and 0.5 months after heart transplantation. Doubling of baseline serum creatinine or attainment of serum creatinine steadily above 176.8 µmol/l (2.0 mg/dl) was used as criterion to define the end-point renal dysfunction. A series of clinical and laboratory variables were obtained from the patients’ charts at different time intervals, and their prognostic value for the occurrence of renal dysfunction was calculated by Cox proportional hazards models. 23 out of 114 patients reached the end point after a median time period of 21 months. High serum triglyceride, alanine aminotransferase, alkaline phosphatase, ciclosporin, urea, glucose, and hemoglobin levels were shown to be associated with the development of renal dysfunction. Four variables, i.e., triglyceride, ciclosporin, urea, and alkaline phosphatase, had an independent prognostic value. Our results confirm a role for ciclosporin in inducing renal dysfunction and identify hyperlipidemia and an increased plasma urea level as risk factors for renal dysfunction in heart transplant recipients.
The Ferroxidase Activity of Caeruloplasmin Is Reduced in Haemodialysis Patients
Authors: Roxborough Heather E. , Mercer Caroline , McMaster Dorothy , Maxwell A. Peter , Young Ian S. 
Published: April 2003

Increased free-radical production leading to oxidative stress may contribute to the development of cardiovascular complications in haemodialysis patients. The ferroxidase activity of caeruloplasmin forms an important component of antioxidant defences in body fluids. The aim of this study was to assess ferroxidase activity in haemodialysis patients. Venous blood was collected from 83 haemodialysis patients immediately prior to and after dialysis and from 52 healthy controls. Immunoreactive caeruloplasmin was measured by rate nephelometry, and ferroxidase activity determined by measuring loading of ferrous iron onto iron-free transferrin. A significant reduction in ferroxidase activity was observed in dialysis patients when compared with controls (37 ± 1.20 and 46 ± 1.14 mU/l, respectively; p < 0.001). Following dialysis, ferroxidase activity rose significantly to 41 ± 1.16 mU/l, with a significant difference still remaining between control and patient ferroxidase activity (p < 0.005). Immunoreactive caeruloplasmin was found to be similar in all groups (before dialysis 0.40 ± 0.07 g/l, after dialysis 0.39 ± 0.07 g/l, control 0.42 ± 0.09 g/l: p = NS). A significant difference in caeruloplasmin-specific activity was therefore observed between predialysis, postdialysis and control samples (97 ± 2.31, 105 ± 1.74 and 112 ± 1.51 mU/g; p < 0.001, p < 0.01, respectively). Ferroxidase activity of caeruloplasmin is impaired in renal failure. Inhibition of caeruloplasmin ferroxidase activity in dialysis patients may contribute to increased oxidative stress in these patients.
Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Prognosis of IgA Nephropathy
Authors: Syrjänen Jaana , Huang Xiao-Hong , Mustonen Jukka , Koivula Timo , Lehtimäki Terho , Pasternack Amos 
Published: April 2003

<i>Background/Aim:</i> Well-known factors for a poor prognosis in IgA nephropathy (IgAN) are hypertension, proteinuria, and renal insufficiency at the time of diagnosis. Also hypertriglyceridemia and hyperuricemia seem to play a role in the progression of IgAN. Angiotensin-converting enzyme (ACE) gene I/D polymorphism has been associated with cardiovascular diseases and with progression of IgAN. We, therefore, investigated the contribution of ACE gene I/D polymorphism in the prognosis of IgAN and its association with the other risk factors affecting the prognosis. <i>Methods:</i> A total of 168 patients with IgAN were followed up for 6–17 (median 11) years from renal biopsy with respect to progression of renal disease defined as elevation of serum creatinine above 125 µ<i>M</i> (1.4 mg/dl) in men or 105 µ<i>M</i> (1.2 mg/dl) in women and over 20% from the baseline level. In addition to serum creatinine, the urinary protein excretion was evaluated at the time of renal biopsy and at the assessment visit at the end of the follow-up period. <i>Results:</i> During the follow-up period, 26 (15%) patients showed progression of renal disease. Patients with ACE genotype II had a more favorable course than those with genotypes ID or DD. Although there were no significant differences among the ACE genotypes with respect to proteinuria ≧1 g/24 h at the time of renal biopsy, proteinuria ≧1 g/24 h was more frequent in patients with genotypes ID or DD than in those with genotype II at the end of the follow-up period. No associations were found between hypertension, serum lipids or serum urate, and ACE genotypes. <i>Conclusions:</i> Our results show that patients with ACE genotype II have a more favorable prognosis than those with genotypes ID/DD. Secondly, proteinuria (≧1 g/24 h) found in patients with genotype II at diagnosis may improve, while in patients with genotypes ID/DD it is a more constant feature.
Low Molecular Weight Heparin in Hemodialysis Patients with a Bleeding Tendency
Authors: Leu Jyh-Gang , Chiang Shou-Shan , Lin Shu-May , Pai Jung-Kuei , Jiang Wey-Wen 
Published: April 2003

Efficacy and safety of a low-molecular-weight heparin (LMWH) were studied in 33 stable maintenance hemodialysis patients who had a bleeding tendency on unfractionated heparin. The optimal dose of LMWH for each patient was titrated before the study; the mean total LMWH dosage was 1,152 ± 574 IU. No major bleeding or clot formation was noted in a total of 2,470 hemodialysis sessions during 6 months of LMWH administration. The mean value of plasma anti-factor Xa (anti-Xa) activity increased from 0.05 ± 0.03 IU/ml before dialysis to 0.34 ± 0.28 IU/ml after 2 h of dialysis and returned to 0.15 ± 0.09 IU/ml after 4 h of dialysis; the mean activated partial thromboplastin time was 26.1 ± 4.4 s before dialysis, 30.7 ± 9.5 s (an 18% increase) after 2 h of dialysis, and 26.2 ± 4.4 s after 4 h of dialysis. No significant change in serum antithrombin levels was noted throughout the whole study period. We conclude that a low dosage of LMWH is safe and effective in hemodialysis patients who have a risk of bleeding with unfractionated heparin. Serum anti-Xa activity is better than activated partial thromboplastin time and antithrombin in assessing the optimal dose of LMWH. A plasma anti-Xa activity of 0.37 IU/ml after 2 h of hemodialysis may represent an optimal dosage of LMWH for most patients.
Transforming Growth Factor-β<sub>1</sub> Inhibits Vascular Permeability Factor Release by T Cells in Normal Subjects and in Patients with Minimal-Change Nephrotic Syndrome
Authors: Matsumoto Koichi , Kanmatsuse Katsuo 
Published: April 2003

<i>Background/Aim:</i> A lymphokine, the vascular permeability factor (VPF), which increases vascular permeability, has been characterized in minimal-change nephrotic syndrome (MCNS). Transforming growth factor-β (TGF-β) is an immunosuppressive cytokine that inhibits proliferation, cytokine production, and cytotoxic activity of T cells and natural killer cells. We, therefore, investigated the effects of TGF-β<sub>1</sub> on the release of VPF by peripheral blood T cells from MCNS patients. The aim of our study was to determine the in vitro immunosuppressive capacity of TGF-β<sub>1</sub> in patients with MCNS. <i>Methods:</i> To further test the effect of TGF-β<sub>1</sub> on concanavalin A (Con A)-induced VPF release, normal and MCNS T cells were stimulated with 5 µg/ml of Con A in the presence or absence of TGF-β<sub>1</sub>, and the culture supernatants were tested for the presence of VPF by the method of Lagrue et al. The disease controls included 16 patients with IgA nephropathy. <i>Results:</i> Significantly increased spontaneous and Con A-stimulated secretion of VPF was detected in T-cell cultures of MCNS patients with the nephrotic syndrome as compared with those of normal controls. Addition of TGF-β<sub>1</sub> to these cultures inhibited the release of VPF in a dose-dependent manner. The effect of TGF-β<sub>1</sub> on the release of VPF was specific, since a reversion was obtained with a neutralizing monoclonal antibody to human TGF-β<sub>1</sub>. <i>Conclusion:</i> Together, our data demonstrate that TGF-β<sub>1</sub> antagonizes the ability of T cells to release VPF, and suggest a role of TGF-β<sub>1</sub> in the pathophysiology of VPF in vitro.
Significance of Salivary Epidermal Growth Factor in Peptic Ulcer Diseasein Hemodialysis Patients
Authors: Guh Jinn-Yuh , Chen Hung-Chun , Chuang Lea-Yea , Yang Chi-Yuan , Tsai Juei-Hsiung , Lai Yung-Hsiung 
Published: April 2003

<i>Background/Aims:</i> Hemodialysis (HD) patients are prone to developing peptic ulcers. However, of all the risk factors associated with peptic ulcers, none have been shown to be more prevalent in HD patients than in the general population. However, salivary epidermal growth factor (EGF) may play a role in peptic ulcer diseases. <i>Methods:</i> Salivary EGF levels and bioactivities were assayed in 47 maintenance HD patients and 30 normal controls, and the molecular weights of EGF were assessed using high-performance liquid chromatography (HPLC). <i>Results:</i> Salivary EGF levels were not different between both groups of subjects (4.2 ± 0.34 vs. 5 ± 0.54 ng/mg protein, NS), and HPLC revealed that salivary EGF in both groups had similar molecular weights. However, salivary EGF bioactivity was significantly depressed in the HD patients as compared to the normal controls (0.59 ± 0.08 vs. 1.55 ± 0.15 ng/mg protein, p < 0.01). Stepwise multiple regression showed that the low salivary EGF levels were associated with female gender (p < 0.05), while low salivary EGF bioactivity was associated with HD per se (p < 0.05). In the 22 HD patients who underwent gastric endoscopy, salivary EGF bioactivity was significantly lower in those with peptic ulcers than in those without (0.38 ± 0.08 vs. 0.69 ± 0.08 ng/mg protein, p < 0.05). <i>Conclusion:</i> Decreased salivary EGF bioactivity may contribute to peptic ulcer disease among maintenance HD patients.
Low Molecular Weight Heparin Reduces Proteinuria and Modulates Glomerular TNF-α Production in the Early Phase of Adriamycin Nephropathy
Authors: Benchetrit S. , Golan E. , Podjarny E. , Green J. , Rashid G. , Bernheim J. , Hershkovitz R. 
Published: April 2003

<i>Background/Aim:</i> Heparin has been shown to be renoprotective in a number of experimental nephropathies. The inflammatory component in the early phase of Adriamycin (ADR) induced nephropathy has been established. A microdose of low molecular weight heparin (Fragmin; F) has been noted to exert immunomodulatory effects independent of its anticoagulant activity. We assessed the effects of microdoses of F on daily proteinuria and glomerular production of tumor necrosis factor alpha (TNF-α) and prostaglandins 8 and 15 days after induction of ADR nephropathy. <i>Methods:</i> Following intravenous injection of ADR (7 mg/kg) to Wistar rats weighing 200 ± 20 g, F 20 µg/day/rat s.c. was administered for 8 and 15 days (groups F8 and F15). The respective control groups (C8 and C15) received normal saline subcutaneously. Proteinuria, serum albumin, and creatinine clearance were evaluated on days 8 and 15. The production of TNF-α and prostaglandins from glomerular supernatants was measured by radioimmunoassay on days 8 and 15. <i>Results:</i> F significantly reduced proteinuria (mg/day) on day 8: 13.6 ± 1.2 in F8 versus 40.3 ± 2.7 in C8 (p = 0.008). The glomerular production of TNF-α (pi/ml) was significantly lower on day 8 in rats treated with F: 356 ± 33 in F8 versus 764 ± 81 in C8 (p = 0.006). A decrease in the prostaglandin E<sub>2</sub>/thromboxane B<sub>2</sub> ratio was noted in the F group between 8 and 15 days (1.1 in F8 vs. 0.9 in F15, p = 0.005) which principally reflects an increase of thromboxane B<sub>2</sub>. The antiproteinuric effect of F shown after 8 days was no longer present after 15 days (354 ± 91 mg/day in F15 vs. 499 ± 69 mg/day in C15, p = 0.33). The same trend was seen for the glomerular production of TNF-α. Light microscopy and immunohistochemistry for interstitial and glomerular macrophages were negative. <i>Conclusion:</i> The lowering effect of microdoses of F on the proteinuria seen during the early phase of ADR nephropathy may be mediated by a decreased production of glomerular TNF-α, supporting the anti-inflammatory action of low molecular weight heparin.
Inhibitory Effects of Nicorandil on Rat Mesangial Cell Proliferation via the Protein Kinase G Pathway
Authors: Segawa Kayoko , Minami Kouichiro , Shiga Yousuke , Shiraishi Munehiro , Sata Takeyoshi , Nakashima Yasuhide , Shigematsu Akio 
Published: April 2003

We investigated the effects of nicorandil, which is a hybrid between a nitrate and an ATP-sensitive potassium channel (K<sub>ATP</sub>) opener, on cultured rat mesangial cell proliferation. Nicorandil (1 µ<i>M</i> to 1 m<i>M</i> inhibited [<sup>3</sup>H]thymidine incorporation into rat mesangial cells in a concentration-dependent manner. Nicorandil (1 µ<i>M</i> to 1 m<i>M</i>) also inhibited the number of cells. Nicorandil increased cyclic guanosine 3′,5′-cyclic monophosphate accumulation in mesangial cells. A protein kinase G inhibitor, KT5823, partially eliminated the inhibition of mesangial cell proliferation by nicorandil. Methylene blue, a guanylate cyclase inhibitor, blocked the inhibitory effect of nicorandil on mesangial cell proliferation. We also examined the effects of K<sub>ATP</sub> mediators. Cromakalim, a K<sub>ATP</sub> activator, and glibenclamide, a K<sub>ATP</sub> inhibitor, had little effect on the proliferation of mesangial cells. These results suggest that the inhibitory effects of nicorandil on mesangial cell proliferation are mediated via the protein kinase G pathway.
Vitamin B<sub>6</sub> Therapy Does Not Improve Hematocrit in Hemodialysis Patients Supplemented with Iron and Erythropoietin
Authors: Weissgarten J. , Modai D. , Oz D. , Chen Levy Z. , Cohn M. , Marcus O. , Dishi V. , Galperin E. , Averbukh Z. 
Published: April 2003

<i>Background/Aim: </i>Pyridoxine deficiency may be the cause of failure to respond appropriately to iron and erythropoietin (EPO) administration in hemodialysis patients. <i>Method:</i> We studied 36 patients on chronic hemodialysis amply supplemented with iron and EPO, who failed to raise hematocrit levels >33%. Patients were divided into three equal groups and evaluated for 6 months as follows: Group A – no additional therapy; group B – supplemented with oral pyridoxine 50 mg/day, and group C received 100 mg/day pyridoxine orally. <i>Results: </i>In all our patients, erythrocyte pyridoxine levels were initially within reference range for a healthy population and did not vary significantly during the study period. Likewise, ferritin levels and iron saturation values remained normal and constant. Hemoglobin and/or hematocrit levels remained practically unchanged in all three groups. <i>Conclusions: </i>The results indicate that in hemodialysis patients with normal pyridoxine status who, despite appropriate supplementation of iron and EPO, fail to reach optimal hematocrit levels, additional pyridoxine treatment does not produce any hematocrit elevation.
Effect of <i>L</i>-Carnitine Supplementation in Hemodialysis Patients
Authors: Veselá E. , Racek J. , Trefil L. , Jankovy’ch V. , Pojer M. 
Published: April 2003

<i>Background/Aim:</i><i>L</i>-Carnitine is important in β-oxidation of fatty acids. A lack of carnitine in hemodialysis patients is caused by insufficient carnitine synthesis and especially by its loss during dialysis. The aim of our study was to test the influence of carnitine supplementation on plasma lipids, red blood cell count, and metabolism of free radicals. <i>Methods:</i> Twelve regularly dialyzed patients (average age 55.5 years, average dialysis treatment period 22.5 months) were given 15 mg/kg <i>L</i>-carnitine intravenously three times weekly (after each hemodialysis session) for 6 months. Laboratory markers of oxidative stress, lipid metabolism, and red blood cell count were measured before the supplementation and then controlled during two 3-month intervals. Nine patients were retested 3 months after the supplementation had ended. <i>Results:</i> All supplemented patients showed increased plasma free carnitine in comparison with the pretreatment values (113.3 ± 11.2 vs. 62.3 ± 16.7 µmol/l, p < 0.001). The proportion of decreased <i>L</i>-carnitine values after hemodialysis was reduced from 79 to 22%. Plasma total cholesterol (4.66 ± 0.30 mmol/l after treatment vs. 5.65 ± 1.53 mmol/l before treatment, p < 0.05) and LDL cholesterol (1.74 ± 0.86 vs. 2.81 ± 1.43 mmol/l, p < 0.05) decreased. The albumin concentration significantly increased from 34.8 ± 7.3 to 46.0 ±5.4 g/l (p < 0.05). Intraerythrocyte reduced glutathione increased from 1.65 ± 0.25 to 2.23 ± 0.16 mmol/l (p < 0.001), and the plasma antioxidant capacity increased from 1.65 ± 0.09 to 2.06 ± 0.17 mmol/l (p < 0.001). At the same time, plasma malondialdehyde decreased from 4.18 ± 0.72 to 3.07 ± 0.35 µmol/l (p < 0.001). The erythropoietin dose could be reduced from an average value of 5,500 to 3,500 U/week. No significant changes in the above-mentioned parameters were observed in a control group of dialyzed patients without <i>L</i>-carnitine supplementation. <i>Conclusion:</i> Regular carnitine supplementation of hemodialysis patients can improve their lipid metabolism, protein nutrition, red blood cell count, and antioxidant status.