EXCRETION OF BIKUNIN AND ITS FRAGMENTS IN THE URINE OF PATIENTS WITH RENAL STONES

PURPOSE: Bikunin is a Kunitz-type protease inhibitor found in serum and urine. It has been implicated in urinary stone formation. This study was designed to investigate the role of urinary bikunin in stone formation. MATERIALS AND METHODS: Urinary concentrations of bikunin were measured in 18 male formers of urinary stones 28 to 74 years old and in 77 healthy controls, including 39 males and 38 females, without urological abnormality. A sensitive competitive solid phase enzyme immunoassay was established for urinary bikunin. Bikunin was also qualitatively assessed by Western blot analysis. RESULTS: The mean urinary bikunin-to-creatinine ratio plus or minus standard deviation in stone formers was significantly elevated compared with that in healthy male and female controls (52.9 +/- 46.0 microg./mg. creatinine versus 28.0 +/- 30.4 and 26.5 +/- 21.7, p = 0.005 and 0.006, respectively). By Western blot analysis all urine samples contained authentic 40 kDa. bikunin species. However, a significantly higher proportion of patients was found to have aberrant 25 kDa. bikunin species compared with controls (10 of 18 or 55.6% versus 15 of 77 or 19.5%, p = 0.002). Experiments on de-glycosylation with chondroitinase ABC, amino acid sequencing of the aberrant bikunin species and calcium oxalate crystal growth inhibition assay demonstrated that the 25 kDa. bikunin fragment was identical to de-glycosylated bikunin and less inhibitory on calcium oxalate crystal growth. CONCLUSIONS: If urinary bikunin is important in the pathogenesis of urolithiasis, its effect is probably attributable to the concentration and degree of glycosylation.     

Usefulness of ultrasensitive prostate-specific antigen assay for early detection of biochemical failure after radical prostatectomy

BACKGROUND: In order to assess whether the prostate-specific antigen (PSA) nadir obtained with an ultrasensitive PSA assay can be used as a prognostic indicator for patients undergoing radical prostatectomy, we investigated it retrospectively. METHODS: Between October 1997 and July 2003, 46 patients underwent radical prostatectomy for prostate cancer at our institution. None of them received preoperative treatment. Levels of PSA were measured with an ultrasensitive PSA assay every 1-3 months after prostatectomy. Biochemical recurrence was defined as a PSA level of 0.2 ng/mL or higher. RESULTS: There was a significant difference in PSA nadir between the biochemical recurrence group and the no recurrence group (P < 0.001). The receiver operating characteristics (ROC) curve gave an optimal cut-off value for PSA nadir of 0.01 ng/mL, demonstrating a significant difference in biochemical recurrence after radical prostatectomy. No patient with a PSA nadir level <0.01 ng/mL showed biochemical failure, while 15 out of 22 patients with PSA nadir levels >or=0.01 ng/mL showed biochemical failure. CONCLUSION: The PSA nadir level obtained using an ultrasensitive PSA assay is an excellent predictor of biochemical recurrence after radical prostatectomy. Early detection of recurrence offers the possibility of early salvage therapy.     

Comparison of two in vivo models for prostate cancer: Orthotopic and intratesticular inoculation of LNCaP or PC-3 cells

BACKGROUND: The critical events in the clinical course of prostate cancer are the occurrence of metastasis and the induction of the hormone-refractory status of the disease. In order to investigate the factors responsible for these events, we need appropriate in vivo models. MATERIALS AND METHODS: Orthotopic and intratesticular models were created by the injection of LNCaP cells or PC-3 cells into the prostate or testis of severe combined immunodeficient mice. RESULTS: LNCaP cells in the intratesticular model showed a higher incidence of tumor formation and lymph node metastasis when compared with those in the orthotopic model, while PC-3 cells were highly tumorigenic and metastastic in both models. A high concentration of androgens might play a role in tumor aggressiveness of LNCaP cells, given that enhanced mRNA expressions of integrin alphaV and vascular endothelial growth factor was induced by dehydrotestosterone administration in vitro. The high expression of metastasis-related genes, including the urokinase plasminogen activator system, metalloproteinases and vascular endothelial growth factor-C, might be attributed to the high metastatic potential in both models. Interestingly, testicular xenografts of LNCaP cells were able to survive on the subcutis back of castrated male mice as well female mice. CONCLUSIONS: Intratesticular models of prostate cancer appear to be suitable for studying the mechanisms of metastasis and for evaluating various treatment strategies.     

Influence of heart surgery on magnesium concentrations in pediatric patients

BACKGROUND: There have been only a few investigations into the effects of cardiopulmonary bypass (CPB) on the magnesium (Mg) concentrations in pediatric patients. The purpose of the present study was to compare the postoperative Mg concentrations and their recovery time to pre-surgical values in pediatric patients undergoing CPB for surgical repair of congenital heart disease. The incidence of dysrhythmia was also determined. METHODS: Twenty-seven pediatric patients undergoing open-heart surgery with CPB were enrolled in this study. Controls were 23 pediatric patients undergoing palliative surgery without CPB. Serum Mg (SMg) concentrations and ionized Mg (iMg) concentrations were measured at four sample points: 24 h before the surgery, immediately after the surgery, 24 h after the surgery and 48 h after the surgery. RESULTS: Serum Mg and iMg concentrations were significantly decreased after open-heart surgery. Immediately after the surgery, the mean SMg concentration was 64.1% and the mean iMg concentration was 68.8% of the pre-surgical values. The concentration of iMg showed quicker recovery than that of SMg, and returned to normal range 48 h after surgery. However, SMg and iMg concentrations after palliative surgery did not show significant differences from the pre-surgical values. The incidence of dysrhythmia was almost the same between the two groups; dysrhythmia was observed in two patients in the open-heart surgery group and in three patients in the palliative surgery group. CONCLUSIONS: Mg concentrations showed significant decrease after CPB; however, they showed quick recovery and did not increase the incidence of dysrhythmia in pediatric patients.     

Acute myeloblasts leukaemia without Philadelphia chromosome developing after interferon therapy for chronic myelocytic leukaemia with Philadelphia chromosome

Summary. We report a patient who developed Philadelphia chromosome negative acute myeloblastic leukaemia with trisomy 8 and trisomy 11 after receiving treatment with alkylating agents and interferon for chronic myelocytic leukaemia positive for Philadelphia chromosome. Leukaemic cells were positive for myeloperoxidase and expressed CD13, CD33 and DR; some expressed CD2, CD4 and CD34. The fluorescence in situ hybridization method revealed that bcr-abl fusion genes were absent from > 90% of the bone marrow cells. The major bcr rearrangement was not detected by Southern blot analysis. We conclude that the leukaemic cells negative for Philadelphia chromosome may have developed as a result of treatment with alkylating agents and interferon in the present case.     

A case of Kabuki make-up syndrome with EBV+ Burkitt's lymphoma

Kabuki make-up syndrome was first reported in 1981 and is characterized by peculiar facies with post natal growth deficiency and mental retardation. Since the first report, approximately 100 cases have been reported, but there have been no reports of tumor development. A case is reported of a patient with Kabuki make-up syndrome who developed malignant lymphoma in his abdomen at the age of 3 years. The tumor was histologically diagnosed as Burkitt's lymphoma and Epstein-Barr virus was detected by in situ hybridization.     

A COMPARATIVE STUDY OF ETHANOL ABSORPTION IN THE CANINE JEJUNUM AFTER PRETREATMENT WITH CYANAMIDE OR PYRAZOLE

This report describes the retardation of ethanol absorptionfrom the intestinal tract and reduction of portal blood flowby high acetaldehyde concentrations in dogs using a jejunalsegment with the vascular supply intact. The cyanamide-pretreatmentgroup (CY), in which an extremely high acetaldehyde concentrationdeveloped, in comparison with the control and pyrazole-pretreated(PY) groups, showed a gradual increase of portal blood ethanol,a 25% reduction in the amount of absorbed ethanol, and an 85%smaller absorption rate constant value (K_a). These facts indicatethat the presence of a high acetaldehyde concentration in theblood results in a reduction of ethanol absorption and retardationof ethanol reaching the systemic circulation. The rapid reductionof portal blood flow and the lower ethanol level in the portalvein observed in the CY group, in comparison with the othertwo groups, also indicate that the reduction of ethanol permeabilitythrough the absorption site to the blood is an important retardingfactor induced by acetaldehyde.     

Effect of macrolide antibiotics on ciliary motility in rabbit airway epithelium in-vitro

Abstract— We have studied ciliary beat frequency (CBF) of rabbit cultured tracheal epithelium by a photoelectric method in-vitro. Addition of erythromycin and roxithromycin increased CBF in a dose-dependent fashion, whereas clarithromycin was without effect. The rank order potency of macrolide was roxithromycin > erythromycin » clarithromycin. The roxithromycin-induced increase in CBF was not altered by propranolol, AA-861, or verapamil, but partially attenuated by indomethacin. Roxithromycin increased intracellular cAMP concentrations. These results suggest that certain macrolides can stimulate airway ciliary motility probably via prostaglandin- and cAMP-dependent regulatory pathways, which may affect mucociliary transport function in the respiratory tract.     

Short-period Double-dosing for Simultaneous Evaluation of Intestinal Absorption and Hepatic Disposition in a Single Conscious Rat Using Cephalexin as Test Drug

A new method has been developed for simultaneous evaluation of local absorption from the intestine into the portal system and local disposition through the liver, and for assessment of the bioavailability of a drug in a single conscious rat. The method is based on the difference between plasma concentrations in portal and systemic blood (PS method). Because cephalexin is known to be absorbed completely from the intestine and not to be eliminated through the liver, it was used as test drug to confirm the validity of the new method. The portal vein and the femoral artery of a rat were simultaneously cannulated and blood samples were obtained from both sites. Two methods of administration, single-dosing and double-dosing, were investigated and the efficacy of double-dosing (DD) was demonstrated. Rats received an intra-arterial (group A) or oral (group B) dose in single-dosing, whereas rats used for double-dosing received an oral dose 3 h after an intra-arterial dose (group C). After administration of cephalexin, the portal and arterial plasma concentrations were determined by HPLC. Groups A and B were monitored for 4 h and group C for 8 h. The portal-blood flow rate was measured by means of an electromagnetic flow-meter. Global and local moments were calculated by trapezoidal integration with extrapolation to infinite time. On the basis of the PS method, the local absorption ratio (F_a) and the mean local absorption time (t?_a) were estimated to be 0.975 ± 0.104 and 2.19 ± 0.51 h, respectively, in group B. By comparing the averaged moments between groups A and B, the extent of bioavailability (F), the mean absorption time (MAT) and the hepatic recovery ratio (F_H) were calculated to be 1.01, 1.92 h and 1.04, respectively. The mean hepatic transit time (t?_H) was negligible. In group C, F_a = 0.936 ± 0.107, t?_H = 1.55 ± 0.32 h, F = 1.08 ± 0.07, MAT = 1.55 ± 0.40 h and F_H = 1.17 ± 0.14 h, the mean values being close to those from groups A and B. In conclusion, the PS method with short-period double-dosing (PS-DD method) can offer an effective means of evaluating the local absorption kinetics of drugs, because F, MAT and F_H are obtained from a single conscious rat, and consequently the standard deviations of the quantities can be quickly estimated.