New treatments for chronic prostatitis/chronic pelvic pain syndrome.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition among men of a wide age range, with detrimental effects on quality of life. The etiology, pathogenesis, and optimal treatment of CP/CPPS remain unknown, although progress has been made in these domains in recent years. A wide variety of pharmacologic and nonpharmacologic therapies have been studied in clinical trials, but most have shown limited efficacy in symptom alleviation. CP/CPPS is increasingly viewed as a condition that involves variable degrees of neuropathic pain. Medications such as gabapentin, pregabalin, memantine, and tricyclic antidepressants are often used in other neuropathic pain conditions and, therefore, are considered potential treatments for CP/CPPS. Few studies of these agents in patients with CP/CPPS have been reported, but future clinical trials should help to determine their utility and to characterize the pathogenetic mechanisms of pain in CP/CPPS. Combining treatment trials with biomarker, genomic, and imaging studies, in addition to epidemiologic and symptom-based assessments, will maximize the ability to probe disease etiology and pathogenesis, as well as identify effective treatment.

p53 mediates interstitial cystitis antiproliferative factor (APF)-induced growth inhibition of human urothelial cells.

Antiproliferative factor (APF) is a sialoglycopeptide elevated in the urine of patients with interstitial cystitis, a urinary bladder disorder of unknown etiology that is characterized by chronic pelvic pain. The present study was directed toward uncovering a pathway through which APF signals. Treatment of human urothelial cells with native APF resulted in growth inhibition accompanied by blockade of cell cycle transit and increased p53. Reduced expression of p53 by RNA interference diminished, while ectopic expression of p53 mimicked, the effects of APF. These are the first findings implicating the network of p53 target genes in urothelial defects associated with interstitial cystitis.

Placental soluble fms-like tyrosine-kinase-1 (sFlt-1) in pregnant women with preeclampsia.

UNLABELLED: The pathophysiology of preeclampsia remains largely unknown. A number of circulating placenta-produced factors have been implicated in causing the endothelial dysfunction and the clinical phenotype characteristic of preeclampsia. AIM: Determination of serum levels of placental soluble fms-like tyrosine-kinase-1 (sFlt-1) in pregnant women with preeclampsia. Eleven pregnant women with preeclampsia and 11 healthy women (controls) were included in the study. Determination of sFlt-1 was done with ELISA. The mean serum sFlt-1 levels of pregnant women with preeclampsia were twice as high as that of women with normal pregnancy. The highest level of sFlt-1 was found in women with severe preeclampsia. In women with mild form of preeclampsia the sFlt-1 level was close to that of the controls. sFlt-1 appears to be involved in the pathogenesis of preeclampsia and its serum levels can be used as a diagnostic marker of preeclampsia.

Effect of mycophenolate mofetil (Cell Cept) in the treatment of immune glomerulopathies.

AIM: To study the effect of mycophenolate mofetil (Cell Cept) in treating patients with various types of chronic glomerulonephritis and other immune nephropathies. MATERIAL AND METHODS: Between 2000 and 2003 we treated 35 patients (18 women, 17 men) with Cell Cept (La Roche). In 32 patients the diagnosis was confirmed by kidney biopsy (immunofluorescence, light and electron microscopy). RESULTS: Treatment with Cell Cept was very successful in 22 of the patients in the study (62.86%). Proteinuria was significantly reduced and firmly maintained well below 0.5 g/l; serum protein levels were elevated to normal values, the edemas disappeared. In 12 patients the drug had a good effect: there was a significant reduction of proteins in the urea within 1.2 - 2.0 g/l, an increase of total protein and albumins in plasma but after three months of treatment. The therapy was with no effect only in one patient with primary amyloidosis of kidneys. CONCLUSIONS: Treatment with mycophenolate mofetil (Cell Cept) is an alternative modality for the management of immune glomerulopathies resistant to conventional and pulse pathogenetic therapeutic regimens. It can be a treatment of first choice.

Autosomal recessive polycystic kidney disease. Clinical and genetic profile. (Review and a case report).

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is a genetic disorder inherited in a recessive manner. The ARPKD gene is located on chromosome 6. The disease is characterised by specific changes in the kidney and liver. AIM: To make a review of modern achievements in studying the clinical, genetic and diagnostic problems concerning ARPKD and contribute an illustrative case. RESULTS: We reviewed modern research on the molecular genetics of autosomal recessive polycystic kidney disease related to PKHD1 gene located on chromosome 6p21-cen, as well as on the role of fibrocystin in the terminal differentiation of the collecting and biliary ductules. The clinical manifestations of the disease in infancy and in early childhood are analysed. A diagnostic algorithm is proposed incorporating both clinical and genetic methods. The illustrative case we reported of a 22-year-old patient with ARPKD supports the view that the disease occurs, though rarely, later than in childhood. CONCLUSION: The authors recommend that in cases with late manifestation of the disease in adolescence with chronic renal failure, possibilities be searched for extracorporeal replacement (renal transplantation) when this is allowed by the complications associated with the congenital liver fibrosis.

Ten-year clinical and ultrasonographic follow-up of siblings from families with autosomal dominant polycystic kidney disease.

We conducted a ten-year clinical and ultrasound follow-up study of 120 siblings with ADPKD (68 men and 52 women, aged 19-40). 40 subjects had polycystic kidney disease. During the study period, the number and size of the cysts increased. Symptoms and signs also changed: at baseline 51% of the subjects were asymptomatic dropping subsequently to 2%. Initially, 32 subjects had 1-5 cysts in one or both kidneys and they were classified as suspected of having ADPKD. Significant changes were found in this group at the end of the follow-up. In 12 of them (37.50%) subsequent ultrasonograms revealed an increase in the number and size of the cysts--i.e. evolution towards ADPKD. None of the subjects in this group had a decrease in the number of cysts. In the control group, three had multiple cysts but most subjects were ultrasonographically negative for polycystic kidney disease. In conclusion, the authors recommend a clinical and ultrasonographic long-term follow-up of subjects at risk for ADPKD which should allow early diagnosis as well as prevention of the complications which result in chronic renal failure.