Development of multiple calculi in the duplex system ureterocele

A 61-year-old man presented complaining of pollakisuria and nocturia. A plain radiograph of his kidney, ureter and bladder and intravenous urography revealed numerous calculi in the upper kidney of his left renal pelvis and ureterocele. A transurethral incision of ureterocele (TUI-ureterocele) and extracorporeal shock wave lithotripsy were performed. On TUI-ureterocele, the many calculi were found to be almost the same size and spherical in form. The postoperative clinical course was uneventful.     

Antitumor Activity and Pharmacokinetics of Estra-1,3,5 (10)-Triene-3,17{beta}-Diol, 3-Benzoate, 17-((4-(4-(Bis (2-Chioroethyl)Amino)Phenyl)-1-Oxobutoxy) Acetate) (Bestrabucil) in Human Tumor Xenografts Serially Transplanted into Nude Mice

Bestrabucil (KM2210), the benzoate of an estradiol-chlorambucilconjugate, was used experimental cancer chemotherapy against13 human tumor xenografts serially transplanted into nude mice,and its pharmacokinetics was studied. The tumors were one esophageal,two gastric, six colon, one cholecystic and three breast carcinomas.Two tumor tissue fragments approximately 3x3x3 mm were inoculatedinto BALB/cA nude mice, which were then treated with KM2210at doses of 100, 200 and 300 mg/Kg/day orally starting 24 hrafter the transplantation or when the tumor reached a weightof 100–300 mg. The concentration of KM2210 and its derivativesin the tumor xenografts, normal muscular tissue and blood wereassayed by high performance liquid chroma-tography. Six out of 13 xenografts were found to be sensitive to KM2210.The concentrations of KM2210 and its derivatives in the tumortissues of the sensitive xenografts were five to 10 times higherthan those in blood and muscular tissue, and the antitumor activitycorrelated well with the area under the curve of active metabolitesof KM2210 in the tumor.     

Correlation of enhanced cell proliferation with decreased density of vitamin D receptor in parathyroid hyperplasia in chronic dialysis patients

Summary: The decreased density of the vitamin D receptor (VDR) plays an important role in the pathogenesis and progression of parathyroid hyperplasia in renal failure. In chronic dialysis patients, VDR density is less in nodular hyperplasia than in diffuse hyperplasia and the difference of cell proliferation has been also suggested by DNA analysis. to prove a more direct correlation between VDR density and cell proliferation, VDR density and proliferating cell nuclear antigen (PCNA) were detected in situ by immunohistochemistry in serial sections of surgically excised parathyroid glands from 10 chronic dialysis patients. Among 28 excised glands, 20 glands were nodular hyperplasia and eight glands were diffuse hyperplasia. Vitamin D receptor positive cells were much fewer in nodular hyperplasia (13.1 ± 4.8%) than in diffuse hyperplasia (383 ± 5.6%). In contrast, mean PCNA positive cell numbers per one 400 x field were much higher in nodular hyperplasia (2.0± 1.2) than in diffuse hyperplasia (0.1±0.2). These two parameters, simultaneously detected in the same area of the serial sections, showed strong negative correlation (r= -0.719, P <0.0001). Remarkable differences in VDR and PCNA were evident between nodules and the surrounding diffuse hyperplasia in the same section. These data suggest more direct relationship between the decrease of VDR density and parathyroid cell proliferation in chronic renal failure as a pathophysiological mechanism.     

Pirfenidone prevents the progression of irreversible glomerular sclerotic lesions in rats

Summary: Pirfenidone (PFD) is a new drug which has been shown to prevent or even reverse the extracellular matrix accumulation in several organs. to examine the effect of PFD on the progressive glomerulosclerosis, we treated model rats with irreversible chronic renal disease per orally with 500 mg/kg bodyweight of PFD per day. the model rats were made by intravenous injection of anti-Thy-1 monoclonal antibody 1-22-3 at 1 h following unilateral nephrectomy, which results in chronic progressive glomerulosclerosis. Twenty-four hours later, 32 female Wistar rats were divided into two groups and were fed standard chow with (PFD group: P) or without PFD (control group: C). All rats were sacrificed on day 42. No significant difference in the bodyweight or the amount of chow intake was observed between the two groups. the remnant kidney was significantly ( P <0.05) heavier in C (2.11 ± 0.15 g) than in P (1.70 ± 0.13 g). This finding, together with light microscopic findings, showed that PFD administration resulted in the prevention of renal hypertrophy. On day 42, proteinuria in P (124.3 ± 31.9 mg/day) was significantly lower than in C (214.6 ± 8.1 mg/day), and P maintained significantly better renal function than C as judged by serum urea nitrogen and creatinine levels. Mean matrix score was less in P (178 ± 17) than in C (225 ± 22). Crescent formation was observed in 17% of glomeruli in P and in 35% in C. Tubulointerstitial lesions were also less severe in P. Furthermore, inflammation and sclerosis indices detected by immunohistochemistry (e.g. ED-1, OX8, TGF-beta α-smooth muscle actin, collagen type I, were less in P). These data suggest that PFD may be a promising agent for the prevention of progressive and irreversible glomerulosclerosis.     

Gel Chromatographic Analysis of Cyclosporin and Its Metabolites in Human Blood Compartments

Gel chromatography combined with specific and non-specific cyclosporin radioimmunoassays was adopted for quantitative analysis of cyclosporin and metabolites in free and protein-bound forms in blood compartments of kidney transplant patients. The analytical method was proved to be useful for the purpose, although plasma protein-bound forms of neither cyclosporin nor metabolites could be quantitated in the system. The present study also provided, by gel chromatographic analysis, additional examples to prove that concentrations of cyclosporin metabolites in blood compartments may not be deduced or inferred simply from those of cyclosporin.     

Nephrogenesis accompanied by vascularisation in the mouse embryonic metanephros transplanted into the adult kidney for the creation of additional nephrons

SUMMARY: Metanephric kidneys of nude mice were transplanted on embryonic day 12 into an adult kidney of the same strain, and the growth of the implants was analysed histochemically to investigate the ontogenesis, structure and function of the newly developed additional nephrons. By using a light microscope, developing nephrons at various stages were observed in the implants growing in the host kidney 7 days after transplantation. Immature nephrons, comprising the nephrogenic zone, were intensely positive for proliferating cell nuclear antigen (PCNA) immunostaining, but were no longer present 14 days after transplantation. Vascular integration was observed between the host and implant tissues. Electron microscopic observation 14 days after transplantation showed that the afferent arterioles together with juxtaglomerular cells had entered the gtomeruli. All of the cell types were identified in the vascularised glomeruli with erythrocytes. the visceral epithelial cells had differentiated foot processes, whereas the endothelium of the glomerular tufts was rather thick in parts, and most of the epithelial and endothelial basement membranes were not fused. Several parts of the uriniferous tubules, including proximal and distal tubules, could be identified, and it was found that many of them had remained immature. Some proximal tubules with well-developed brush-border microvilli reabsorbed the horseradish peroxidase (HRP) injected into the host inferior vena cava, thus providing evidence of glomerular ultrafiltration in the vascularised implants perfused by the host. These findings indicate that the nephrogenesis in the implants followed a nearly normal developmental route and showed marked vascularisation, which promoted the organogenesis of the implanted metanephros and nephron function.     

Discrepant effects of vasoconstrictors on the growth of early passaged cultured rat mesangial cells

Summary: Mesangial cell growth stimulation by endothelin (ET) and arginine vasopressin (AVP) has been reported, but only in studies using late (3 times) pasaged cells. In the present study, we examined the effects of ET, AVP and platelet activating factor (PAF) on the proliferation of early (<3 times) passaged cultured rat mesangial cells which maintained their original characteristics. Cell growth was estimated by [³H]-thymidine incorporation into DNA and by counting cell nuclei. After 48 h preincubation in minimal essential medium containing 0.5% fetal calf serum, ET-1 (1-100 nmol/L), AVP (100 pmol/L-1 μmol/L) or PAF (1–100 nmol/L) was added to the incubation medium. In contrast to studies using late passaged cells, ET-1 attenuated and AVP did not increase thymidine uptake (ET-1: 18.4% inhibition at 10 nmol/L) or cell counts in early passaged cells, while the growth stimulatory effects of these agents were reproduced in late passaged cells. Platelet activating factor showed definite stimulation of cell growth in both early and late passaged cells in a dose-dependent manner. These data strongly suggest that ET-1 attenuates, and AVP does not stimulate, the cell growth of original mesangial cells. the PAF-induced cell growth seems to be the constant feature of mesangial cells in vivo.     

Intestinal mast cell response and mucosal defence against Strongyloides venezuelensis in interleukin-3-hyporesponsive mice

Recently several inbred strains of mice were found to be hyporesponsive to Interleukin (IL)-3 because of a 5-bp deletion in the intron 7 of the gene that encodes IL-3 receptor α subunit (IL-3Rα). Due to this mutation, mast cells were not generated in vitro from bone marrow cells of these mice under the presence of IL-3. Intestinal mucosal mast cells, of which growth/differentiation is dependent on IL-3, are important effector cells in immune-mediated expulsion of intestinal nematodes, Strongyloides spp. In the present study, therefore, we examined intestinal mast cell response and mucosal defence against Strongyloides venezuelensis in IL-3-hyporesponsive C58/J and A/J mice. After subcutaneous inoculation with 10 000 infective larvae, C58/J and IL-3-responsive C57BL/6 mice showed identical kinetic patterns of daily faecal egg output and intestinal mast cell response. When these mice were infected with 3000 L3 and, five weeks later, they were challenged by intraduodenal implantation of 800 S. venezuelensis adult worms, the timing of logarithmic decline of faecal egg count as well as intestinal mastocytosis was delayed for two days in C58/J mice. Kinetics of intestinal mastocytosis and faecal egg excretion after a primary and challenge infection in A/J mice, another IL-3-hyporesponsive strain, were identical with those seen in C58/J mice. These results suggest that intestinal mast cell response and mucosal defence against S. venezuelensis of the mutant mice were almost completely compensated in vivo . Possible mechanisms of induction of intestinal mast cell response in IL-3Rα-defective mice are discussed .