Protective role of nebivolol via AKT1/Hif-1α/eNOS signaling pathway: nephrotoxicity caused by methotrexate in a rat model.

Methotrexate (MTX) is an antineoplastic and anti-inflammatory agent, which is used in severe diseases. Its use should be limited due to side effects such as nephrotoxicity, myelotoxicity, and hepatotoxicity. Nebivolol (NBV), which is a beta-blocker used in the treatment of hypertension, also contributes to vasodilation in tissues by activating the endothelial nitric oxide synthase (eNOS) enzyme. The purpose of this study is to research the effect of NBV on MTX-induced nephrotoxicity through the AKT1/hypoxia-inducible factor 1-alpha (Hif-1α)/eNOS signaling pathway. The rats were randomly divided into three groups of eight each. The groups were control, MTX, and MTX + NBV. A single dose of 20 mg/kg MTX was given intraperitoneally to the rats on the first day of the study and 10 mg/kg NBV was given orally to the treatment group for 7 days. At the end of the study, rats' blood and kidney tissues were taken for histopathological, immunohistochemical, and biochemical examinations. MTX administration significantly decreased the expression levels of AKT1, eNOS, and Hif-1α compared with the control group (p < 0.001 for all), and NBV treatment increased these values compared with the MTX group (p < 0.001 for all). In conclusion, NBV treatment ameliorated the MTX-induced nephrotoxicity via AKT1/Hif-1α/eNOS signaling pathway.

Ring chromosome 21 and monosomy 21 mosaicism in a patient with azoospermia.

In this report, we describe a patient with azoospermia in conjection with de novo ring chromosome 21 and monosomy 21 mosaicism. Inter-phase fluorescence in situ hybridisation (FISH) studies on uncultured peripheral blood and epithelial cells obtained by buccal smear revealed that 25% of the uncultured blood cells and 11% of the epithelial cells were monosomic for chromosome 21. Y chromosome microdeletion analysis ruled out the presence of any genomic deletions in the azoospermic factor a,b,c regions on the long arm of chromosome Y. Additionally, through subtelomeric FISH analysis, it was found that there was no deletion in the subtelomeric region of ring chromosome 21. Our results indicate that ring chromosome 21 is a rare, but recurrent chromosomal abnormality in male factor infertility. Furthermore, in individuals with ring chromosome 21, defective spermatogenesis is not associated with the deletion of any gene or genes located in the subtelomeric region of chromosome 21.

Urinary fibronectin levels in patients treated with intravesical bacillus Calmette-Guérin for superficial bladder cancer.

Intravesical bacillus Calmette-Guérin (BCG) has been shown to be an effective treatment for superficial transitional cell carcinoma (TCC) of the bladder, but the precise mechanism of action of BCG remains poorly understood. Fibronectin (FN), an important component of the extracellular matrix, has been found to play a role in BCG therapy. Some studies have shown that the soluble form of FN can compete efficiently with the matrix form of binding to the specific receptors on the bacteria and could consequently diminish the effect of BCG treatment. To evaluate a possible correlation between the urinary levels of FN and the efficacy of BCG therapy, we determined prospectively the urinary FN levels in 38 patients with TCC of the bladder and in 25 control subjects without malignancy matched for age and sex. All TCC patients were treated with transurethral tumor resection plus 6 weekly intravesical BCG instillations. After an average follow-up of 30 months, 8 patients (21.1%) had recurrent tumors, while 30 (78.9%) were free of tumor after intravesical BCG therapy. Urinary levels of FN in cancer patients have been shown to be significantly higher than controls (p < 0.001). These elevated levels were not decreased significantly after the operation (p > 0. 05). It was also found that the mean urinary FN levels were not statistically significant between patients with recurrence and complete remission. The data suggest that BCG-bladder tumor cell binding is not influenced by soluble fibronectin and urinary FN may not be a ideal marker for selecting patients to BCG therapy.

Do renal failure and hemodialysis have any effect on the elimination of free and total prostate-specific antigen?

OBJECTIVES: The aim of this study was first to determine the serum levels of free prostate-specific antigen (f-PSA), total prostate-specific antigen (t-PSA) and f-PSA/t-PSA ratios in patients with renal failure, and secondary, to investigate whether a significant difference between serum f-PSA and t-PSA levels consists in patients with end-stage renal disease before and after hemodialysis. METHODS: Serum concentrations of f-PSA and t-PSA were measured in 36 men with end-stage renal disease before and after hemodialysis and in 95 healthy controls. A chemiluminescent enzyme assay was used to determine the levels of f-PSA and t-PSA. RESULTS: The mean concentrations of serum t-PSA were 1.36+/-0.43 ng/ml in patients on hemodialysis and 1.08+/-0.60 ng/ml in controls. There was no significant difference in f-PSA and t-PSA levels between patients with renal failure and controls. F-PSA and t-PSA levels in patients with renal failure also showed no statistical differences before and after hemodialysis. CONCLUSIONS: The limited kidney reserve in patients with end-stage renal disease is sufficient to maintain the levels of t-PSA and f-PSA within normal ranges and hemodialysis does not alter the serum levels of different PSA forms.

Serum free and total prostate-specific antigen levels in patients with liver disease.

OBJECTIVES: To determine the effect of liver diseases on serum free prostate-specific antigen (fPSA) levels, total prostate-specific antigen (tPSA) levels, and fPSA/tPSA ratios. METHODS: Serum concentrations of tPSA and fPSA were measured in 18 men with histologically confirmed liver cirrhosis, 20 men with histologically proved chronic hepatitis, and 20 healthy men. All patients underwent a standard urologic evaluation, including history, physical examination, urine analysis, serum fPSA and tPSA determinations, and liver function tests (serum bilirubin, serum glutamic oxaloacetic transaminase, and serum glutamic pyruvic transaminase). RESULTS: Patients with liver cirrhosis had slightly lower fPSA levels than did control subjects or patients with chronic hepatitis, but these differences did not reach statistical significance. tPSA levels also were not significantly different among the three groups. CONCLUSIONS: In the presence of liver disease, despite the limited liver reserve, tPSA and fPSA are specific and reliable markers in the clinical management of prostatic diseases in this population. This result should be taken into account when serum concentrations of fPSA, tPSA, and the fPSA/tPSA ratio are evaluated in patients with liver disease.

Ratio of free to total prostate-specific antigen in patients with prostatic intraepithelial neoplasia.

OBJECTIVE: There are many reports about the effects of prostatic intraepithelial neoplasia (PIN) on serum prostate-specific antigen (PSA) level. The aim of this study was to determine the relationship between PIN and serum free PSA/total PSA (fPSA/tPSA) ratios. METHODS: We evaluated 46 patients with PIN, 15 patients with benign prostatic hyperplasia (BPH), and 16 patients with localized prostatic carcinoma (CaP) for the amount of fPSA and tPSA with the chemiluminescent enzyme assay. RESULTS: fPSA values from BPH to high-grade PIN (PIN2 and PIN3) was increased, and then a decrease was observed from high-grade PIN to CaP. fPSA was significantly different between BPH and low-grade PIN and high-grade PIN. There was no significant difference observed between BPH and CaP. tPSA values increased from BPH to CaP. tPSA was significantly different between BPH and high-grade PIN and CaP. fPSA/tPSA ratios decreased from BPH to CaP. This ratio was significantly different between CaP and BPH and low-grade PIN. There was no significant difference between CaP and high-grade PIN. CONCLUSIONS: Our results confirm that fPSA/tPSA ratio is better at discriminating between patients with CaP and those with BPH, but not between patients with CaP and those with high-grade PIN. Due to similarities between CaP and high-grade PIN, we think that decreased fPSA/tPSA ratio obtained at the time of intial diagnosis of PIN without concurrent carcinoma could be used as predictive factors to distinguish patients in whom carcinoma will be found on subsequent biopsies from those with PIN not associated with cancer on repeat biopsy.

Determination of the site of metabolism of total, free, and complexed prostate-specific antigen.

OBJECTIVES: To determine the site of metabolism of total prostate-specific antigen (tPSA), free PSA (fPSA), and complexed PSA (cPSA). METHODS: A total of 20 male patients, 50 years old or older, having a clinical indication for left and right heart catheterization were enrolled in this study. Selective blood samples were obtained from the infrarenal, infrahepatic, and suprahepatic inferior vena cava, renal vein, hepatic vein, superior vena cava, pulmonary artery, and femoral artery. cPSA concentration was accepted as the difference between tPSA and fPSA concentrations. RESULTS: We found that tPSA and fPSA concentrations in the infrarenal inferior vena cava were significantly higher than in the systemic artery. There was no significant difference between the systemic artery and the infrarenal inferior vena cava for cPSA concentration. Although fPSA concentration decreased significantly across the renal circulation, the decreases in cPSA and tPSA concentrations were statistically insignificant. In the hepatic circulation, we found that tPSA, fPSA, and cPSA concentrations were significantly decreased. No decrease in tPSA, fPSA, and cPSA concentrations were noted across the pulmonary circulation. CONCLUSIONS: Our results indicate that fPSA and tPSA are released into serum from the prostate but the prostate may not have a significant role in complex formation of PSA. In addition, the liver has a significant role in the elimination of tPSA, fPSA, and cPSA. By contrast, the kidneys have a significant role only in the elimination of fPSA. We also found that the lungs did not have a significant role in the elimination of tPSA, fPSA, or cPSA.

Morbidity associated with patient positioning in extracorporeal shock wave lithotripsy of distal ureteral calculi.

In 115 patients with 123 distal ureteral stones located below the lower border of the sacroiliac joint, in situ extracorporeal shock wave lithotripsy (ESWL) was performed with a Siemens Lithostar Lithotriptor. Our initial experience with the prone position in 8 out of 49 cases did not reveal stone fragmentation and on the final treatment sessions shock waves were allowed to enter via the obturator or sciatic foramen whilst the patients were in the supine position, in order to compare the results of treatments performed in both positions. The mean number of treatment sessions per patient, mean number of shock waves per treatment sessions, mean shock voltage per session and mean fluoroscopy time per session were significantly lower in the supine group than in the prone group (p < 0.05 for all variables). ESWL of the distal ureteral stones in the prone position seems to have an associated patient morbidity when we compare the results of treatments performed in both positions.

Milk of calcium hydronephrosis.

There are very few reported cases of 'milk of renal calcium' since Holm's first presentation of this rare condition in 1948 [Rosenberg, J. Urol., 101: 714, 1967]. We recently had the opportunity to study 2 more cases, which are described herein.