Biomedical subjects

Yan Lu

Publications and source records attributed to Yan Lu.

At least 127 records · Page 7Linked to original sources

PubMed2003

RAGE drives the development of glomerulosclerosis and implicates podocyte activation in the pathogenesis of diabetic nephropathy.

Diabetic nephropathy ensues from events involving earliest changes in the glomeruli and podocytes, followed by accumulation of extracellular matrix in the mesangium. Postulated mechanisms include roles for vascular endothelial growth factor (VEGF), produced by podocytes and contributing to enhanced excretion of urinary albumin and recruitment/activation of inflammatory cells, and transforming growth factor-beta (TGF-beta), elicited largely from mesangial cells and driving production of extracellular matrix. RAGE, a receptor for advanced glycation endproducts (AGEs) and S100/calgranulins, displays enhanced expression in podocytes of genetically diabetic db/db mice by age 13 weeks. RAGE-bearing podocytes express high levels of VEGF by this time, in parallel with enhanced recruitment of mononuclear phagocytes to the glomeruli; events prevented by blockade of RAGE. By age 27 weeks, soluble RAGE-treated db/db mice displayed diminished albuminuria and glomerulosclerosis, and improved renal function. Diabetic homozygous RAGE null mice failed to develop significantly increased mesangial matrix expansion or thickening of the glomerular basement membrane. We propose that activation of RAGE contributes to expression of VEGF and enhanced attraction/activation of inflammatory cells in the diabetic glomerulus, thereby setting the stage for mesangial activation and TGF-beta production; processes which converge to cause albuminuria and glomerulosclerosis.

Albuminuria↗

PubMed2003

A method for marker-assisted selection based on QTLs with epistatic effects.

A method for marker-assisted selection (MAS) based on quantitative trait loci (QTLs) with epistatic effects is proposed. The efficiency of such method is investigated by simulations under a wide range of situations. In the presence of epistasis, MAS generally yields longer persistence response than that based exclusively on additive or additive and dominance. Neglecting epistasis could result in considerable loss in response, and more pronounced at later generations. In addition to population size and trait heritability, genetic variance configurations play an important role in determining both the short- and long-term efficiencies of MAS. MAS using breeding values not only achieves higher response, but also tends to have smaller standard error than other methods in most cases. Errors in QTL detection cause distinct reductions in responses to MAS in most cases. It is thus concluded that verifications of putative QTL and its magnitude of effect and accurate map chromosome location are imperative to realize the potentials of MAS.

Epistasis, Genetic↗

PubMed2003

Efficacy of 19-Nor-1,25-(OH)2D2 in the prevention and treatment of hyperparathyroid bone disease in experimental uremia.

BACKGROUND: The control of parathyroid hyperplasia and high circulating parathyroid hormone (PTH) levels is crucial in preventing secondary hyperparathyroidism (SH) in renal failure. Parathyroid gland enlargement and elevated levels of PTH are major contributors to increase bone resorption, a feature of renal osteodystrophy. METHODS: These studies assessed the efficacy of the 1,25(OH)2D3 analog, 19-Nor-1,25(OH)2D2 (19-Nor), in the prevention (protocol I) and treatment (protocol II) of SH and renal osteodystrophy in uremic rats. In protocol I, normal and uremic rats were fed a high phosphorus diet for 2 months; uremic rats were administered intraperitoneal injections of either vehicle or 19-Nor (200 ng three times a week). In protocol II, normal and uremic rats were fed a high phosphorus diet for 4 months; 2 months after the onset of uremia, rats were administered either intraperitoneal vehicle or 19-Nor (200 ng three times a week). Serum PTH and bone histology were used to assess the degree of SH. RESULTS: 19-Nor was effective in preventing (protocol I) and suppressing (protocol II) the significant SH induced by uremia and further enhanced by a high phosphorus diet. In protocol I, bone histology in uremic controls showed a threefold increase in the cancellous bone mass compared to normal rats. This expansion in unmineralized bone was accompanied by 5-, 1.5-, and 7-fold increases in eroded surface, mineralization lag time (MLT), and bone formation rate (BFR/BS), respectively. Moreover, cortical bone porosity in untreated uremic rats increased 267-fold compared to normal animals. 19-Nor ameliorated these changes in cancellous and cortical bone. In protocol II, the reported indices worsened even further. In contrast, 2 months of 19-Nor treatment improved bone histology by reducing cortical bone porosity, woven bone formation, MLT, and BFR/BS. CONCLUSION: In an experimental model of chronic renal failure (CRF), 19-Nor prevents SH and ameliorates the histomorphometric changes induced by uremia and high phosphorus diet. In addition, 19-Nor suppresses serum PTH and improves bone histology in uremic rats with established severe SH. Further studies in patients with CRF are necessary to define the clinical applicability of 19-Nor on bone histology in humans.

Animals↗

PubMed2003

Multiplex PCR assay for identification of human diarrheagenic Escherichia coli.

A multiplex PCR assay for the identification of human diarrheagenic Escherichia coli was developed. The targets selected for each category were eae for enteropathogenic E. coli, stx for Shiga toxin-producing E. coli, elt and est for enterotoxigenic E. coli, ipaH for enteroinvasive E. coli, and aggR for enteroaggregative E. coli. This assay allowed the categorization of a diarrheagenic E. coli strain in a single reaction tube.

Diarrhea↗

PubMed2003

[Expression of estrogen receptor beta in the hypothalamic paraventricular nucleus of postnatal female mice].

Previous studies have revealed that estrogen receptor beta (ER-beta) in the mouse hypothalamic paraventricular nucleus (PVN) may play different roles from that in the PVN of rat and other animal species. In the present study, the expression of ER-beta in the developing PVN of postnatal female mice was studied using nickel ammonium sulfate intensified immunocytochemical techniques, and the results showed that ER-beta immunopositive materials were predominantly localized in the magnocellular division of the PVN, only sparse positive cells were found in the parvocellular division and dorsal cap of the PVN. Most of the positive cells were strongly labeled, but some lightly labeled cells were also detected. No apparent positive signals were observed in the cytoplasm or the processes of the neurons. The highest levels of expression were found at early postnatal days (postnatal day 1 to 9), and then it decreased to lower levels from day 15 and thereafter. The above results together with other findings suggest that at early postnatal development, ER-beta may play important role in the regulation of the structure and function of PVN, such as neuroendocrine, morphological maturation, food intake and body weight increase of postnatal animals.

Animals↗

PubMed2003

[T(H1) and T(H2) cells in children with mycoplasma pneumonia].

OBJECTIVE: To Study T lymphocyte subsets, including T(H1) and T(H2) cells in peripheral blood mononuclear cells (PBMC) of children with mycoplasma pneumonia, understand immunopathogenesis and explore the possibility of immunotherapy of patients with mycoplasma pneumonia. METHODS: Fresh peripheral blood samples of patients from two groups, group 1, mycoplasma pneumonia (MP) group (35 cases, 15 males and 20 females, age range 3 - 13 years, mean 9 years), and control group consisted of 28 healthy children (14 males and 14 females, age range 3 - 12 years, mean 7 years) were treated and run through the flow cytometry. The data were obtained by using Simultest IMK-Lymphocyte software and the percentage of CD(3)(+), CD(3)(+)CD(4)(+), CD(3)(+)CD(8)(+), CD(3)(-)CD(19)(+) and CD(3)(-)CD(16 + 56)(+) cells were counted. The percentage of T(H1) and T(H2) cells were gained through determination of intracellular cytokines IFN-gamma or IL-4 in CD(4)(+) cells by flow cytometry. The 35 patients with MP were hospitalized at our hospital. In addition to fever and cough, all the patents had abnormal X-ray findings and/or moist rale on auscultation of the lungs. The IgM antibody to Mycoplasma pneumoniae was positive in each patient. Immunoglobulins were measured, and PPD skin tests were performed in 30 out of the 35 patients with MP. T test and rank sum test by SPSS FOR WINDOWS 10.0 was used for statistical analysis. RESULTS: The percentage of CD(3)(+) and CD(4)(+) T lymphocyte was 68.00 +/- 6.66 and 37.86 +/- 5.84, respectively, in MP group, and 63.71 +/- 7.92 and 34.54 +/- 6.23 in control group (P < 0.05). The percentage of T(H1) cells was 14.13 +/- 8.46 in patients and 20.77 +/- 6.89 in normal control group (P = 0.001). The percentage of NK cells was 15.57 +/- 12.16 and 20.39 +/- 9.64 in MP and control group (P < 0.01). The ratio of T(H1)/T(H2) in MP group was lower than that in control group (P < 0.05). However the percentage of CD(8), T(H2), B cells and CD(4)/CD(8) had no difference between the MP and control groups. The levels of IgG, IgA, and IgM in serum were normal in most of patients except for a few patients who had elevated IgA and IgM levels. The PPD skin tests were negative in 30 out of 35 patients. CONCLUSION: In this study a higher percentage of CD(3)(+), CD(4)(+) T lymphocyte and lower percentage of T(H1), NK cells in PBMC of patients with mycoplasma pneumonia were found. The ratio of T(H1) and T(H2) cells in patients was also lower. None of thirty patients had positive PPD skin tests. Unbalanced cell-mediated immunity with a tendency toward T(H2) existed in patients with MP. Therefore, immunomodulators may be useful in treatment of mycoplasma pneumonia.

Adolescent↗

PubMed2002

RAGE blockade stabilizes established atherosclerosis in diabetic apolipoprotein E-null mice.

BACKGROUND: Previous studies suggested that blockade of RAGE in diabetic apolipoprotein (apo) E-null mice suppressed early acceleration of atherosclerosis. A critical test of the potential applicability of RAGE blockade to clinical settings was its ability to impact established vascular disease. In this study, we tested the hypothesis that RAGE contributed to lesion progression in established atherosclerosis in diabetic apoE-null mice. METHODS AND RESULTS: Male apoE-null mice, age 6 weeks, were rendered diabetic with streptozotocin or treated with citrate buffer. At age 14 weeks, certain mice were killed or treated with once-daily murine soluble RAGE or albumin; all mice were killed at age 20 weeks. Compared with diabetic mice at age 14 weeks, albumin-treated animals displayed increased atherosclerotic lesion area and complexity. In diabetic mice treated with sRAGE from age 14 to 20 weeks, lesion area and complexity were significantly reduced and not statistically different from those observed in diabetic mice at age 14 weeks. In parallel, decreased parameters of inflammation and mononuclear phagocyte and smooth muscle cell activation were observed. CONCLUSIONS: RAGE contributes not only to accelerated lesion formation in diabetic apoE-null mice but also to lesion progression. Blockade of RAGE may be a novel strategy to stabilize atherosclerosis and vascular inflammation in established diabetes.

Animals↗

PubMed2002

Determination of lomefloxacin by terbium sensitized chemiluminescence method.

A simple, rapid and sensitive chemiluminescence (CL) method was proposed for the determination of lomefloxacin (LFX). This method is based on the fact that the weak CL from the redox reaction of Ce(4+)-Na(2)SO(3) can be greatly enhanced by the complex of Tb(3+)-LFX. The CL intensity is directly proportional to the concentration of LFX in the range 2.0x10(-9) to 1.0x10(-5) mol L(-1), and the detection limit (S/N=3) is 1.1x10(-9) mol L(-1). This method has been applied to the detection of LFX in pharmaceutical preparation, urine and serum samples. Recoveries were in the range 95-105%. The CL mechanism of Ce(4+)-Na(2)SO(3)-Tb(3+)-LFX system was proposed to be an intermolecular energy transfer from excited SO(2)(*) to LFX and an intramolecular energy transfer from LFX to Tb(3+).

Anti-Infective Agents↗

PubMed2002

1,25-Dihydroxyvitamin D down-regulates cell membrane growth- and nuclear growth-promoting signals by the epidermal growth factor receptor.

1,25(OH)(2)D(3) antiproliferative properties are widely known. However, the molecular bases of these properties are only partially elucidated. Since 1,25(OH)(2)D(3) effectively arrests growth in many tumors and hyperplastic tissues whose growth is driven by co-expression of EGFR and its ligand TGF-alpha, it was hypothesized that 1,25(OH)(2)D(3) could affect the TGF-alpha/EGFR-autocrine growth loop. This study examined 1,25(OH)(2)D(3) regulation of EGFR-growth signals, using human epidermoid A431 cells, in which the overexpression of EGFR and TGF-alpha constitute the major autocrine mitogenic signal. 1,25(OH)(2)D(3) inhibited autocrine and EGF-induced A431 cell proliferation. Furthermore, 1,25(OH)(2)D(3) changed the cellular localization of both TGF-alpha and EGFR and inhibited ligand-dependent phosphorylation of EGFR and ERK1/2. In addition, 1,25(OH)(2)D(3) impaired autocrine and EGF-induced nuclear translocation of activated EGFR and, consequently, its binding to AT-rich DNA sequences and transcriptional activation of the cyclin D1 promoter. These results demonstrate that 1,25(OH)(2)D(3) alters EGFR membrane trafficking and down-regulates EGFR growth signaling.

Animals↗

PubMed2002

Molecular recognition through the exact placement of functional groups on non-covalent molecularly imprinted polymers.

To investigate the extent of the placement of functional groups in the non-covalent molecularly imprinted polymers contributing to selectivity, three kinds of molecularly imprinted methacrylic acid-ethylene glycol dimethacrylate copolymers were prepared at higher polymerization temperature (60 degrees C) using 2-L-phenylalanylamino-pyridine, 3-L-phenylalanylamino-pyridine, or 4-L-phenylalanylamino-pyridine as a template molecule, respectively. The enantiomeric recognition performance of these molecularly imprinted polymers (MIPs) in the high-performance liquid chromatography (HPLC) mode was investigated. The polymers exhibited efficient enantiomeric resolution of the racemic mixture of their printing molecules and could hardly resolve the enantiomers of other substrates that were structurally analogous to the imprinting molecules, but different from spatial interaction sites on the polymer with the methacrylic acid residues. Our results showed that the shape and spatial orientation of functionality of imprinted binding sites were critical for recognition and the recognition properties of MIPs were greatly influenced by the minor difference of N position on the pyridine ring and caused by the distance accuracy of functional groups in the binding sites. The implication of these findings with respect of the mechanism of recognition was discussed.

Chromatography, High Pressure Liquid↗

PubMed2002

Cooperative action of ADMP- and BMP-mediated pathways in regulating cell fates in the zebrafish gastrula.

It was shown in Xenopus and chick that Spemann's organizer activity is regulated through the negative action of Anti-Dorsalizing Morphogenetic Protein (ADMP). We report the characterization and functional properties of admp in zebrafish. admp expression profile is consistent with a role in the organizer, including the tail organizer. We studied admp function through overexpression experiments, with the use of a dominant-negative form (TR-ADMP) and of an antisense morpholino-modified oligonucleotide. Our results indicate that the ADMP pathway causes the restriction of anterior and axial fates and that ADMP, BMP2b, and BMP7 pathways have distinct actions but cooperate in establishing proper dorso-ventral regionalization. This is shown by partial rescue of the dorsalized mutant snailhouse and of the ventralized mutant chordino, upon admp and tr-admp RNA injection, respectively. Moreover, ADMP and BMP7 probably form heterodimers as shown by the ability of TR-ADMP and BMP7 to antagonize each other. We observed that a MYC-tagged ADMP was secreted and detected in the extracellular space, suggesting that admp could act at a distance. Simultaneous local inhibition of bmp function at the blastoderm margin and impairment of ADMP secretion led to the induction of secondary head structures, confirming that the two pathways cooperatively regulate organizer formation and activity.

Amino Acid Sequence↗

PubMed2002

Receptor for advanced glycation endproducts (RAGE) and vascular inflammation: insights into the pathogenesis of macrovascular complications in diabetes.

The incidence and severity of atherosclerosis is increased in patients with diabetes. Indeed, accelerated macrovascular disease in diabetic patients has emerged as a leading cause of morbidity and mortality in the United States and worldwide. Multiple investigations have suggested that there are numerous potential contributory factors that underlie these observations. Our laboratory has focused on the contribution of receptor for advanced glycation endproducts (RAGE) and its proinflammatory ligands, advanced glycation endproducts (AGEs) and S100/calgranulins in vascular perturbation, manifested as enhanced atherogenesis or accelerated restenosis after angioplasty. In rodent models of diabetic complications, blockade of RAGE suppressed vascular hyperpermeability, accelerated atherosclerotic lesion area and complexity in diabetic apolipoprotein E-deficient mice, and prevented exaggerated neointimal formation in hyperglycemic fatty Zucker rats subjected to injury of the carotid artery. In this review, we summarize these findings and provide an overview of distinct mechanisms that contribute to the development of accelerated diabetic macrovascular disease. Insights into therapeutic strategies to prevent or interrupt these processes are presented.

Animals↗

PubMed2002

The basic science of thermally assisted chondroplasty.

Thermal chondroplasty provides a visually enticing effect on articular cartilage, but the long-term effects of thermal modification and injury to articular cartilage must be understood before the technology is applied to cartilage and chondrocytes in a clinical setting.

Arthroscopy↗

PubMed2002

Detection of EspB using reversed passive latex agglutination: application to determination of enteropathogenic Escherichia coli.

We developed a new practical method to identify enteropathogenic Escherichia coli (EPEC) by detecting the pathogenic factor, EspB. E. coli were cultured in Dulbecco's Modification of Eagle's Medium (DMEM), and EspB was detected in the culture supernatant by reversed passive latex agglutination (RPLA). All 63 E. coli strains harboring the eaeA gene encoding intimin were positive for RPLA, and all 25 strains without the eaeA gene were negative. Among these 63 eaeA-positive strains, 38 Shiga toxin-producing E. coli (STEC) produced Shiga toxin (Stx) under the same culture conditions (DMEM). Subtypes of EspB alpha, beta and gamma were antigenically cross-reactive to each other as determined by RPLA and Western blotting. A kit for Stx detection (RPLA) is commercially available and therefore this RPLA for detection of EspB could be a practical method to define EPEC in both clinical laboratories and the field.

Antibodies, Bacterial↗

PubMed2002

Melanocytes are potential immunocompetent cells: evidence from recognition of immunological characteristics of cultured human melanocytes.

The dendritic nature, the strategic location, and other accumulated evidence about the immunologic characteristics of melanocytes suggest that they are not only professional melanin producing cells but are also immunocompetent cells. In this study, we demonstrated that cultured melanocytes express low levels of some immunologically important surface markers such as intercellular adhesion molecule-1 and CD 40. Moreover, we report for the first time CD 40 expression by melanocytes can be up-regulated by interferon-gamma (IFN-gamma) stimulation. Optimal enhancement of CD 40 expression was observed at an IFN-gamma concentration of 300 U/ml after a co-culture period of 72 h. Maximal melanocyte-driven T lymphocyte proliferation and interleukin-12 secretion were also observed following the same treatment and proved to be CD 40-dependent. Our data further suggest that upon CD 40 ligation, melanocytes up-regulate their co-stimulating and adhesion molecules. In addition to previous descriptions about the melanocyte's antigen processing and presenting capacity, we therefore hypothesize a dynamic model in which melanocytes alternatively work as heterogeneous antigen presenting cells. As a result of CD 40 expression on the cell surface, melanocytes might contact and subsequently stimulate CD8+ cytotoxic T lymphocytes directly via CD 40-CD 40 L interaction in some cases.

Adult↗

PubMed2002

Thermometric determination of cartilage matrix temperatures during thermal chondroplasty: comparison of bipolar and monopolar radiofrequency devices.

PURPOSE: To compare cartilage matrix temperatures between monopolar radiofrequency energy (mRFE) and bipolar RFE (bRFE) at 3 depths under the articular surface during thermal chondroplasty. We hypothesized that cartilage temperatures would be higher at all cartilage depths for the bRFE device than for the mRFE device. TYPE OF STUDY: Randomized trial using bovine cartilage. METHODS: Sixty osteochondral sections from the femoropatellar joint of 15 adult cattle were used for this study. Using a custom jig, fluoroptic thermometry probes were placed at one of the following depths under the articular surface: 200 microm, 500 microm, or 2,000 microm. RF treatment was performed either with fluid flow (F) (120 mL/min) or without fluid flow (NF) (n = 5/depth/RFE device/flow; total specimens, 60). Irrigation fluid temperature was room temperature (22 degrees C). Thermometry data were acquired at 4 Hz for 5 seconds with the RF probe off, for 20 seconds with the RF probe on, and then for 15 seconds with the RF probe off. During RF treatment, a 0.79-cm2 area (1.0-cm diameter) of the articular surface centered over the thermometry probe was treated in a paintbrush manner in noncontact (bRFE) or light contact (mRFE). RESULTS: Thermal chondroplasty with bRFE resulted in higher cartilage matrix temperatures compared with mRFE for all depths and regardless of fluid flow. Bipolar RFE resulted in temperatures of 95 degrees C to 100 degrees C at 200 microm and 500 microm under the surface, with temperatures of 75 degrees C to 78 degrees C at 2,000 microm. Fluid flow during bRFE application had no effect at 200 microm. Monopolar RFE resulted in temperatures of 61 degrees C to 68 degrees C at 200 microm, 54 degrees C to 70 degrees C at 500 microm under the surface, and 28 degrees C to 30 degrees C at 2,000 microm below the surface. A significant effect of fluid flow during mRFE application occurred at 200 microm (NF, 61 degrees C; F, 63 degrees C) and 500 microm (NF, 53 degrees C; F, 68 degrees C). CONCLUSIONS: In this study, we found significant differences between bRFE and a temperature-controlled mRFE device with regard to depth of thermal heating of cartilage in vitro. Bipolar RFE resulted in matrix temperatures high enough (>70 degrees C) to kill cells as deep as 2,000 microm under the articular surface. Fluid flow during thermal chondroplasty had the effect of significantly increasing cartilage matrix temperatures at 200 and 500 microm with the mRFE device. During thermal chondroplasty, bRFE creates greater matrix temperature elevations at equivalent depths and treatment duration than does mRFE. Excessive temperatures generated deep within the cartilage matrix could cause full-thickness chondrocyte death, in vivo.

Animals↗

PubMed2002

Thermal chondroplasty with bipolar and monopolar radiofrequency energy: effect of treatment time on chondrocyte death and surface contouring.

PURPOSE: The purpose of this study was to evaluate chondrocyte viability and surface contouring of articular cartilage using confocal laser microscopy (CLM) and scanning electron microscopy (SEM), respectively, during different treatment time intervals with monopolar and bipolar radiofrequency energy (RFE). TYPE OF STUDY: In vitro analysis using chondromalacic human cartilage. METHODS: Forty-two fresh osteochondral sections from patients undergoing partial or total knee arthroplasties were used to complete this study. Each of 36 sections was divided into 2 distinct 1-cm(2) regions that were treated with either bipolar or monopolar RFE. Six sections were maintained as untreated controls. Six RF treatment time intervals were evaluated: 5, 10, 15, 20, 30, and 40 seconds (6 specimens per time interval per group). After treatment, each specimen was processed for CLM and SEM. RESULTS: CLM demonstrated that the depth of chondrocyte death in the monopolar RFE treatment group was significantly less than the bipolar group at each of the same time intervals (P <.05). SEM showed that each RFE device began to contour and smooth the articular surface after 15 seconds of treatment. CONCLUSIONS: When applying thermal chondroplasty, a broad treatment time range could result in variable degrees of cartilage smoothness and significant chondrocyte death.

Aged↗

PubMed2002

The effects of sevelamer hydrochloride and calcium carbonate on kidney calcification in uremic rats.

The control of serum phosphorus (P) and calcium-phosphate (Ca x P) product is critical to the prevention of ectopic calcification in chronic renal failure (CRF). Whereas calcium (Ca) salts, the most commonly used phosphate binders, markedly increase serum Ca and positive Ca balance, the new calcium- and aluminum-free phosphate binder, sevelamer hydrochloride (RenaGel), reduces serum P without altering serum Ca in hemodialysis patients. Using an experimental model of CRF, these studies compare sevelamer and calcium carbonate (CaCO(3)) in the control of serum P, secondary hyperparathyroidism (SH), and ectopic calcifications. 5/6 nephrectomized rats underwent one of the following treatments for 3 mo: uremic + high-P diet (U-HP); UHP + 3% CaCO(3) (U-HP+C); UHP + 3% sevelamer (U-HP+S). Sevelamer treatment controlled serum P independent of increases in serum Ca, thus reducing serum Ca x P product and further deterioration of renal function, as indicated by the highest creatinine clearances. Sevelamer was as effective as CaCO(3) in the control of high-P-induced SH, as shown by similar serum PTH levels, parathyroid (PT) gland weight, and markers of PT hyperplasia. Also, both P binders elicited similar efficacy in reducing the myocardial and hepatic calcifications induced by uremia. However, sevelamer caused a dramatic reduction of renal Ca deposition (29.8 +/- 8.6 micro g/g wet tissue) compared with both U-HP (175.5 +/- 45.7 micro g/g wet tissue, P < 0.01) and the U-HP+C (58.9 +/- 13.7 micro g/g wet tissue, P < 0.04). Histochemical analyses using Von Kossa and Alizarin red S staining of kidney sections confirmed these findings. The high number of foci of calcification in the kidney of uremic controls (108 +/- 25) was reduced to 33.0 +/- 11.3 by CaCO(3) and decreased even further with sevelamer (16.4 +/- 8.9, P < 0.02 versus CaCO(3)). Importantly, the degree of tubulointerstitial fibrosis was also markedly lower in U-HP+S (5%) compared with either U-HP+C (30%) or U-HP (50%). It is concluded that in experimental CRF in rats, despite a similar control of serum P and SH, sevelamer is more effective than CaCO(3) in preventing renal Ca deposition and tubulointerstitial fibrosis, including better preservation of renal function. These findings cannot be extrapolated to human disease, and further studies in patients are necessary to determine the benefits of either P binder.

Animals↗