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Platelet-activating factor (PAF), a potent phospholipid chemical mediator of inflammation, is involved in multiple cellular functions. Since PAF has a strong effect on platelet aggregation and on the enhancement of capillary permeability, it is possible that this factor plays an important role in tumor progression. In human renal cell carcinoma (RCC), it has recently been reported that immunotherapy with interferon (IFN) is effective for the prevention of tumor recurrence and progression. To evaluate the role of PAF and the effect of interferon-alpha (IFN-alpha) on PAF production in RCC, we measured PAF content and the activity of choline phosphotransferase (CPT), an enzyme involved in the de novo biosynthesis of PAF, in RCC specimens obtained from 30 patients who had undergone radical nephrectomy for RCC, and in specimens of normal renal cortex and normal renal medulla. PAF was present in both RCC and the normal renal tissues. Although CPT activity in RCC was similar to that in normal renal cortex, CPT activity in the normal medulla was significantly higher than that in RCC and the normal cortex. No correlation was found between CPT activity and the pathological findings in RCC. Although there was no difference in CPT activity in normal renal tissues between patients treated preoperatively with IFN-alpha and those untreated, CPT activity in RCC was significantly reduced in patients who had received IFN-alpha compared with those who had not. These findings suggest that IFN-alpha may modulate the production of PAF in RCC patients.

We previously have shown an increase in muscarinic receptor density in streptozotocin (STZ)-induced diabetic and sucrose-fed diuretic rat detrusor that correlates with an increase in the contractile response to muscarinic agonist (J Pharmacol Exp Ther 248:81, 1989; Diabetes 40: 265, 1991). To investigate the signal transduction pathway involved in this altered functional response, we examined muscarinic receptor-coupled phosphatidylinositol metabolism in STZ-diabetic, sucrose-fed diuretic and age-matched control rat bladders. [3H]myo-inositol uptake was similar in all groups, but incorporation of myo-inositol into phosphatidylinositol (PI) was significantly increased in the diabetic bladder compared to the sucrose-fed and control rat bladders. Carbachol-induced increase in inositol phosphate (IPs) production was higher in the diabetic bladder than in bladders from control and sucrose-fed animals although the EC50 values were similar for all groups. Enhanced inositol phosphate production after muscarinic agonist stimulation may be due not only to the upregulation of muscarinic receptors but also the increased incorporation of myo-inositol into PI in the STZ-induced diabetic bladder.

The regulation of prostaglandin (PG) synthesis was characterized in microsomes of bovine bladder epithelium. Coenzyme A (CoA) and its metabolite cysteamine drastically decreased total PG synthesis. Furthermore, CoA inhibited solubilized cyclooxygenase which was precipitated by anti-cyclooxygenase antibody. Reduced glutathione (GSH) slightly increased total PG production and changed the pattern of PG synthesis. Other thiols, cysteine and ergothioneine, did not change total PG production. None of the thiols stimulated the incorporation of arachidonic acid into the phospholipid fraction. These findings suggest that CoA may directly regulate cyclooxygenase activity and GSH may subsequently change the pattern of PG production in bovine bladder epithelium.

Spinal cord injury (SCI) at Th13 was induced in female Wistar rats, and changes in the urinary bladder were examined during the acute phase of SCI. Wet weights of the spinal bladders increased twofold over controls by 7 days after SCI. Intravesical volumes increased sixfold over control values by day 3, and then decreased 7 days after the injury. Maximal pressure within the bladder decreased in all spinal rats compared with controls. Smooth muscle cells were isolated from the urinary bladder, and their total protein and DNA content were measured by multiparametric cytofluorometry. DNA content of isolated smooth muscle cells decreased by day 3 and remained 7 days after the spinal injury. Total protein content of isolated smooth muscle cells was decreased 1 day after and increased 7 days after the spinal injury, just when spinal reflex of the bladder recovered. These findings suggest that hypertrophy of smooth muscle cells in urinary bladder is related to the activity of peripheral autonomic nerve and that smooth muscle cells already begin to hypertrophy during the spinal shock period to adjust themselves to the new state, that is, the spinal bladder.

A congenital arteriovenous fistula (AV fistula) in the true pelvis is extremely rare, especially in males. We present a case of this disease with pollakiuria and intrarectal discomfort. Diagnosis was made by computed tomography and magnetic resonance imaging and confirmed by cine angiography. Because the AV fistula involved the bladder, prostate and rectum, ligation of the main feeding arteries was performed. He also had benign prostatic hypertrophy and was treated by conservative therapy because of a high risk of massive bleeding in surgical treatment.

Membrane fluidity and lipid composition of rat testis in experimental bilateral cryptorchidism were studied. Membrane fluidity measured by fluorescence anisotropy of diphenylhexatriene decreased on the 3rd day of intraabdominal fixation, at an early stage of cryptorchidism. Lipid composition of testicular membrane was changed drastically by the treatment, and time-dependent changes were observed during the course of the experiment. Cholesterol content increased significantly, but phospholipid content was not affected by the treatment. The ratio of cholesterol to phospholipids increased significantly. Fatty acid moieties of phospholipids varied during the course of the experiment. The ratio of unsaturated to saturated fatty acids decreased on the 3rd day. These changes indicated a different physical state of cryptorchid membranes from normals, and the changes may be involved in the pathophysiology of cryptorchidism.

A possible mechanism is presented by which reduced glutathione (GSH) regulates prostaglandin (PG) synthesis in microsomes of the porcine bladder epithelium. At a concentration of GSH less than 10(-5) M, microsomes produced more PGI2 and PGF2 alpha than PGE2. At a greater GSH concentration, PGE2 synthesis was remarkably enhanced. On the other hand, PGI2 and PGF2 alpha synthesis was inhibited. In the presence of 10(-3) M GSH, ten times more PGE2 was produced than the other PGs. The concentration of GSH in porcine bladder epithelium was about 0.6 mM. This reciprocal effect of GSH was also observed in rabbit and bovine bladder epithelium. These findings suggest that GSH is involved in the regulation of PG synthesis in urinary bladder epithelium. GSH may influence the physiological and pathophysiological changes elicited by PGs in the lower urinary tract.