Zinc deficiency further increases the enhanced expression of endothelin-1 in glomeruli of the obstructed kidney.
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BACKGROUND: Zinc (Zn) is an essential trace element in humans and animals. We have recently documented that Zn deficiency may aggravate tubulointerstitial nephropathy seen in the obstructed kidney (OK) of 72 hours duration through a further increase in the activity of endogenous angiotensin II in the OK. Also, it is known that the vasoconstrictors angiotensin II and endothelin (ET)-1 may be implicated in the deterioration of glomerular hemodynamics caused in the OK. We therefore designed the present study to examine the effect of Zn deficiency on the expression of ET-1 and a potential role of endogenous angiotensin II in the expression of ET-1 in glomeruli of the OK of 72 hours duration. METHODS: Using reverse transcription-polymerase chain reaction and immunohistochemistry, the expression of prepro-ET-1 mRNA and ET-1 was examined in glomeruli of the contralateral, non-obstructed control kidney (CLK) and the OK from rats with unilateral ureteral obstruction (UUO) of 72 hours duration fed a standard or a Zn-deficient diet for approximately 50 days. The rats in each group were treated with saline alone or the angiotensin-converting enzyme inhibitor enalapril before and after ureteral obstruction. RESULTS: The expression of prepro-ET-1 mRNA and ET-1 was markedly greater in the OK than in the CLK in the standard and the Zn-deficient diet groups. However, the expression of prepro-ET-1 mRNA and ET-1 was substantially increased in the OK of the Zn-deficient diet group relative to the OK of the standard diet group. There were no significant differences in the expression of prepro-ET-1 mRNA and ET-1 between the CLK of the two diet groups. Administration of enalapril restored the expression of prepro-ET-1 mRNA and ET-1 in the OK to levels seen in the CLK in the standard and the Zn-deficient diet groups. Enalapril produced no effects on the expression of prepro-ET-1 mRNA and ET-1 in the CLK of the two diet groups. CONCLUSIONS: UUO of 72 hours duration may increase the expression of prepro-ET-1 mRNA and ET-1 in glomeruli of the OK through an increment in the biological action of endogenous angiotensin II in the OK. Moreover, Zn deficiency may enhance the expression of prepro-ET-1 mRNA and ET-1 in glomeruli of the OK through a further increment in the biological action of endogenous angiotensin II in the OK. Zn deficiency appears to be a factor to worsen glomerular hemodynamics in the OK of the UUO setting of 72 hours duration through an increment in the biological action of the vasoconstrictors angiotensin II and ET-1. (+info)
Laparoscopic treatment of retroperitoneal fibrosis: report of two cases and review of the literature.
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OBJECTIVES: We present the results of treatment by laparoscopy of two patients with retroperitoneal fibrosis and review the literature since 1992, when the first case of this disease that was treated using laparoscopy was published. We also discuss the contemporary alternatives of clinical treatment with corticosteroids and tamoxifen. CASE REPORT: Two female patients, one with idiopathic retroperitoneal fibrosis, and other with retroperitoneal fibrosis associated with Riedel's thyroiditis, were treated using laparoscopic surgery. Both cases had bilateral pelvic ureteral obstruction and were treated using the same technique: transperitoneal laparoscopy, medial mobilization of both colons, liberation of both ureters from the fibrosis, and intraperitonealisation of the ureters. Double-J catheters were inserted before the operations and removed 3 weeks after the procedures. The first patient underwent intraperitonealisation of both ureters in a single procedure. The other had 2 different surgical procedures because of technical difficulties during the first operation. Both patients were followed for more than 1 year and recovered completely from the renal insufficiency. One of them still has occasional vague lumbar pain. There were no abnormalities in the intravenous pyelography in either case. CONCLUSIONS: Surgical correction of retroperitoneal fibrosis, when indicated, should be attempted using laparoscopy. If possible, bilateral ureterolysis and intraperitonealisation of both ureters should be performed in the same operation. (+info)
Bladder outflow obstruction masquerading as pelviureteric junction (PUJ) obstruction.
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We report a case of bladder outflow obstruction presenting with upper tract dilatation mistaken initially as pelviureteric junction (PUJ) obstruction. The lower tract obstruction ought to be dealt with first before upper tract obstruction is assessed because the renal pelvic pressure is significantly affected by vesical filling and high bladder pressure. (+info)
Up-regulation of the tumour-associated marker CD44V6 in experimental kidney disease.
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CD44 is an adhesion molecule involved in a wide range of cell-cell and cell-matrix interactions. The standard form of CD44 (CD44S) is a 85-90-kD glycoprotein, but alternative splicing of RNA encoding 10 variable exons (V1-V10) can give rise to many different CD44 variant protein isoforms of higher molecular weight. CD44 isoforms containing the V6 exon play a crucial role in tumour metastasis and lymphocyte activation. However, the role of CD44V6 in the kidney is unknown. The aim of this study was to examined renal CD44V6 expression in health, disease and in vitro. Immunohistochemistry staining with the V6-specific 1.1ASML antibody identified constitutive CD44V6 expression by occasional cortical tubular epithelial cells and medullary tubules in normal rat kidney. In immune-induced kidney disease (rat anti-glomerular basement membrane glomerulonephritis), there was a marked increase in CD44V6 expression by cortical tubules, particularly in areas of tubulointerstitial damage, which was associated with focal macrophage infiltration. There was also a marked increase in CD44V6 expression by damaged tubules in a model of non-immune kidney disease (unilateral ureteric obstruction). Reverse transcription-polymerase chain reaction revealed a complex pattern of CD44V6-containing mRNA isoforms in normal rat kidney. This pattern of CD44V6 splicing was essentially unaltered in disease. The NRK52E normal rat kidney tubular epithelial cell line expresses both CD44S and CD44V6. Stimulation of NRK52E cells with IL-1 or transforming growth factor-beta 1 induced a two-to-five-fold increase in the expression of both CD44S and CD44V6. Furthermore, triggering of NRK52E cells by antibodies to CD44S or CD44V6, but not isotype control antibodies, induced secretion of monocyte chemoattractant protein-1. In conclusion, this study has identified expression of the tumour-associated marker CD44V6 in tubular epithelial cells in normal and diseased rat kidney, and suggests that signalling through the CD44V6 molecule may participate in the pathogenesis of experimental kidney disease. (+info)
TIMP-1 gene expression and PAI-1 antigen after unilateral ureteral obstruction in the adult male rat.
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BACKGROUND: Sustained obstruction of urinary flow invariably leads to inflammation, loss of functional renal structures and progressive deposition of extracellular matrix proteins, culminating in renal fibrosis. Although increased renal tissue inhibitor of matrix metalloproteinase (TIMP-1) expression is one of the early events following experimental hydronephrosis, little is known about its cellular source. Both the recruited macrophage and the resident/recruited (myo)fibroblast have been postulated to be candidate TIMP-1 transcribing cells. Currently, data concerning plasminogen activator inhibitor type 1 (PAI-1) expression in the ligated kidney are unavailable. Our study concentrated on the localization of TIMP-1 expressing cells and PAI-1 immunoreactive cells in the obstructed rat kidney. METHODS: Rats were sacrificed 1, 5, 10, 15, 20 and 26 days after unilateral ureteral obstruction (UUO) or sham-surgery (SOR). Leukocyte (OX-1+), macrophage (ED1+) and neutrophil infiltration were analyzed using specific antibodies or nuclear morphology. alpha-Smooth muscle actin (alpha-SMA) immunostaining was measured morphometrically. Mitotic figures and nuclei with an apoptotic morphology were quantified in hematoxylin-eosin (H&E)-stained sections. TIMP-1 mRNA transcribing cells were localized with in situ hybridization (ISH) and identified by subsequent immunostainings for alpha-SMA and macrophages. PAI-1 antigenicity was evaluated immunohistochemically in SOR, contralateral unobstructed kidneys (CUK), and UUO kidneys. RESULTS: The number of leukocytes and macrophages in the ligated rat kidney increased progressively in time, starting from day 5 post-surgery when compared with CUKs. Neutrophil accumulation in UUO kidneys became apparent from day 5 and large intraluminal leukocyte clusters (neutrophils and macrophages) were found in the lumen of distended tubules, especially at later stages post-obstruction, when collected urine and tissue samples proved to be sterile upon culture. From day 5 on, the number of apoptotic cells started to predominate the number of mitotic cells in the obstructed kidneys. Interstitial alpha-SMA immunoreactivity in the ligated kidney expanded from day 5 on and was most pronounced in the inner stripe of the outer medulla. As early as 24 hours post-ligation, TIMP-1 mRNA transcribing interstitial cells were detected with ISH, while tubular TIMP-1 expression was sparse. Since at that point in time, no interstitial alpha-SMA expressing cells and only few ED1+ macrophages were present, the bulk of the TIMP-1 mRNA transcription occurred in other interstitial cells. Throughout the study period numerous interstitial TIMP-1 expressing cells were detectable in obstructed kidneys and from day 5 after ligation on, we could identify alpha-SMA+ and to a lesser degree ED1+ macrophages as TIMP-1 transcribing cells. In addition, dilated tubules containing intraluminal leukocyte casts were surrounded by a corona of intact neutrophils in H&E-stained sections and ISH showed that similar tubules were encircled by TIMP-1 mRNA expressing cells. PAI-1 immunoreactivity appeared to diminish in the early phase following urinary outlet obstruction, but emerged in damaged tubules from day 5 to 10 on. In later stages post-ligation, PAI-1+ cells and PAI-1 immunoreactive material were found embedded in the extracellular matrix. CONCLUSIONS: Our results confirm that TIMP-1 is active in the early phase of the fibrotic process and we demonstrated that initially TIMP-1 mRNA is transcribed by very few ED1+ macrophages but mainly by other, presently unidentified, interstitial cells. During later stages of post-ligation, both TIMP-1 (transcribed among others by alpha-SMA+ myofibroblasts, ED1+ macrophages, and possibly neutrophils) and PAI-1 are involved in the progression of tubulointerstitial scarring. (+info)
Holmium laser incision technique for ureteral stricture using a small-caliber ureteroscope.
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BACKGROUND AND OBJECTIVES: The holmium laser has a short absorption depth in tissue and possesses excellent properties both in ablation and hemostasis. We have performed endoscopic incision for ureteral stricture using the holmium laser through a small-caliber ureteroscope. METHODS: This method was used on five patients and seven ureters. The etiology of the stricture was stone scar in two patients, ureteroenteroanastomosis of Indiana urinary pouch in two, and primary in one. We used an 8F semi-rigid or 6.9F flexible ureteroscope. No prior procedures, such as balloon dilation, were necessary in any of the cases. The stricture was incised with the holmium laser using a 365-microm fiber through the working channel of the ureteroscope. The holmium laser operated at a wavelength of 2100 nm, with an output of 1.0 J/pulse at a rate of 10 Hz. After completion of the incision, a 12F Double-J catheter was left in for six weeks. RESULTS: The mean operative time was 89 minutes. The stricture resolved completely in all cases at an average follow-up of 8.6 months. CONCLUSIONS: The holmium laser incision for ureteral stricture using a small-caliber ureteroscope is an easy-to-perform, safe and effective procedure. (+info)
An ultrastructural study of the renal medulla in experimental acute pyelonephritis.
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Experimental acute pyelonephritis was produced in rats by a combination of intravenous administration of Escherichia coli, strain IMRU-54, and temporary unilateral mechanical ureteral obstruction. Structural alterations of the renal medulla were studied by light and electron microscopy. Major cellular alterations occurred in the vasa recta. Tubular and interstitial cells demonstrated minimal alterations after the brief period of acute inflammation. Polymorphonuclear leukocytes within tubular lumina contained structures resembling E. coli in nonprotoplasts-like form. Numerous protoplast-like organisms, to the exclusion of any other structural forms, were detected within the interstitium of the inner medulla. Nonprotoplast-like structures resembling E. coli were rarely observed in interstitium of the inner medulla. Following relief of ureteral obstruction, clearance of acute inflammation was rapid. In conclusion, hemoatogenous acute pyelonephritis induced by E. coli, IMRU-54, is able to inflict cytological and ultrastructural damage to structural elements of the inner and outer medulla of rats. Vasa recta incurred prominent alterations in endothelia and basement membranes, whereas tubular epithelia and interstitial cells had relatively good structural preservation. The data suggest that intravenously administered E. coli is capable to revert to a protoplast-like structure in the inner medulla. (+info)
Mechanism of chronic obstructive uropathy: increased expression of apoptosis-promoting molecules.
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BACKGROUND: We have demonstrated that renal tubular and interstitial cells undergo pronounced apoptosis during the course of chronic obstructive uropathy (COU). Apoptosis is a complex cellular process consisting of multiple steps, each of which is mediated by families of related molecules. These families may include receptor/ligand molecules such as Fas, Fas ligand, tumor necrosis factor receptor-1 (TNFR-1), and TNF-related apoptosis inducing ligand (TRAIL); signal transduction adapter molecules such as Fas-associated death domain (FADD), TNFR-1 associated death domain (TRADD), receptor-interacting protein (RIP), Fas-associated factor (FAF), and Fas-associated phosphatase (FAP); or effector molecules such as caspases. However, the mechanism of tubular cell apoptosis, as well as the pathogenetic relevance of these apoptosis-related molecules in COU, remains poorly understood. METHODS: Kidneys were harvested from sham-operated control mice and mice with COU created by left ureter ligation sacrificed in groups of three at days 4, 15, 30, and 45. To detect apoptotic tubular and interstitial cells, in situ end labeling of fragmented DNA was performed. To detect the expression of apoptosis-related molecules, ribonuclease protection assay was used with specific antisense RNA probes for Fas, Fas ligand, TNFR-1, TRAIL, FADD, TRADD, RIP, FAF, FAP, and caspase-8. Immunostaining for Fas, Fas ligand, TRAIL, TRADD, RIP, and caspase-8 was also performed. To assess the role of these molecules in COU-associated renal cell apoptosis, the frequencies of apoptotic tubular and interstitial cells were separately quantitated for each experimental time point, and their patterns of variation were correlated with those of apoptosis-related molecules. RESULTS: The obstructed kidneys displayed increased apoptosis of both tubular and interstitial cells. Tubular cell apoptosis appeared at day 4 after ureter ligation, peaked (fivefold of control) at day 15, and decreased gradually until the end of the experiment. In contrast, interstitial cell apoptosis sustained a progressive increase throughout the experiment. Apoptosis was minimal at all experimental time points for control and contralateral kidneys. Compared with control and contralateral kidneys, the ligated kidneys displayed a dynamic expression of mRNAs for many apoptosis-related molecules, which included an up to threefold increase for Fas, Fas ligand, TNF-R1, TRAIL, TRADD, RIP, and caspase-8, and an up to twofold increase for FADD and FAP, but there was little change for FAF. These mRNAs increased between days 4 and 15, decreased until day 30, but then increased again until day 45. The rise and fall of mRNAs between days 4 and 30 paralleled a similar fluctuation in tubular cell apoptosis in that period. The subsequent increase of mRNAs was correlated with a continuous rise of interstitial cell apoptosis. We demonstrated a positive immunostaining for Fas and Fas ligand in the tubular cells at early time points as well as in interstitial inflammatory cells at later time points. Although increased expression of TRAIL, TRADD, RIP, and caspase-8 was noted in tubular cells, there was no staining for these molecules in interstitial cells. CONCLUSION: The current study documents a dynamic expression of several molecules that are known to mediate the most crucial steps of apoptosis. It implicates these molecules in COU-associated renal cell apoptosis and in the pathogenesis of this condition. It also lays the foundation for interventional studies, including genetic engineering, to evaluate the molecular control of apoptosis associated with COU. (+info)