Tumor necrosis factor alpha and glutathione interplay in chronic heart failure.

The pro-inflammatory cytokine, tumor necrosis factor alpha (TNF alpha), in concert with neurohormones, contributes to chronic heart failure (CHF) progression. This implies that TNF a antagonism may constitute an important target for CHF therapy. However, clinical trials in CHF patients using compounds that trap TNF alpha, comprising infliximab, an antibody directed to TNF alpha, and etanercept, a soluble recombinant receptor of TNF alpha, gave disappointing results bringing back to light the dual, short-term beneficial and long-term harmful effect of TNF alpha. This review focuses on the dual, concentration- and time-related effects of TNF alpha, the yin and yang action of TNF alpha in cardiac ischemia/reperfusion and contraction. Importantly, the harmful effects of TNF a are related to glutathione deficiency, a common hallmark to several other chronic inflammatory diseases. Recently, in rat models of CHF, oral administration of the glutathione precursor, N-acetylcysteine (NAC), was shown to hinder pathways of TNF alpha harmful signalling and to rescue cardiac structure and function. These results suggest that glutathione deficiency in association with TNF alpha activation may play a role in the pathophysiology of CHF and that NAC may represent a potential therapy in CHF.

In search of a 24 hours per day artificial kidney.

Wearable, 24 hrs per day, 7 days per week artificial kidneys are being developed. Patients will benefit from more even control of physiologic parameters than can be obtained with conventional intermittent dialysis. Improvement in economic and social circumstances will result. Both hemodialysis and peritoneal dialysis techniques are being miniaturized. Small REDY cartridges containing urease, zirconium phosphate, hydrouse zirconium oxide and activated carbon are being utilized to regenerate dialysate. Hemodialyzers will be worn on the forearm and include long, wide, low resistance series blood flow paths to reduce the potential for thrombosis. Peritoneal effluent is regenerated and filtered by the sorbent cartridge and automatically cycled back into the peritoneal cavity.

Development of a sorbent peritoneal dialysate regeneration system--a progress report.

A sorbent regenerative dialysate system for peritoneal dialysis has been developed (Pericycle). Clinical results and data demonstrate that the sorbent system provides a suitable dialysate. The sorbents effectively remove uraemic metabolites from the dialysate. Calcium and magnesium removed by the cartridge and glucose metabolised by the patient are replaced by the infusion system. The machine pumps regenerated dialysate into and spent dialysate out of the patients. A pressure sensor in the patient line prevents excessive inflow and outflow pressures by stopping the inflow or outflow pump respectively. The Pericycle provides a simple, safe, portable method for conducting peritoneal dialysis in the home or hospital.

Applications of the Redy sorbent system to hemodialysis and peritoneal dialysis.

The application of sorbent technology to the treatment of uremia has been limited by the inability to adsorb urea adequately. Conversion of urea to ammonium carbonate and adsorption by zirconium phosphate provides a practical means of removing urea. This combination, together with hydrated zirconium oxide and carbon, removes uremic waste products from dialysate. Over 1500 patients are undergoing maintenance hemodialysis with this system. The dialysate composition can be modified for the treatment of patients with acute renal failure. This sorbent system is now being used for the regeneration of peritoneal dialysate. Twenty patients have undergone a total of 90 dialyses, each of 4 to 24 hours duration. One home patient has been solely on this system for two months. The application of sorbent technology to peritoneal dialysis may be the most promising approach to a wearable dialysis system.