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We compared the efficacy and safety of apheresis and reinfusion of concentrated ascites (ARCA) versus total paracentesis plus intravenous albumin (PARA) in a prospective trial on cirrhotic patients with tense ascites. Twenty-four patients were randomized to either ARCA (N = 12) or PARA (N = 12), and followed for two years. Sex, age, Child's class, and renal and liver function were similar in the two groups. The times the procedures were 2.7 +/- 1.0 (ARCA) vs 2.2 +/- 1.1 (PARA) hr, with removal of 8.8 +/- 3.5 (ARCA) and 6.9 +/- 3.4 (PARA) liters of ascites and intravenous infusion of 59.8 +/- 35.2 (ARCA) and 42.5 +/- 20.5 (PARA) g of albumin. Both procedures were safe. Biochemical signs of coagulative disturbances having no clinical relevance were observed after ARCA, with an increase in prothrombin time (P = 0.005) and serum FSP (P = 0.02). No significant changes in renal function, serum albumin, or plasma and urinary electrocytes were shown. Plasma renin activity increased after PARA (P = 0.02) and plasma atrial natriuretic factor increased after ARCA (P = 0.008), although no differences were observed in diuresis in the immediate follow-up. During the long-term follow-up, patient survival and recurrence of tense ascites were the same in both groups. We conclude that apheresis and reinfusion of concentrated ascites are as safe and effective as total paracentesis with albumin infusion for the treatment of tense ascites in cirrhotic patients.

Ascites is a common complication of chronic liver disease. Treatment of the underlying liver disease with modalities such as abstinence from alcohol in Laennec's cirrhosis, phlebotomy in hemochromatosis, copper removal in Wilson's disease, and steroids in autoimmune liver disease, can improve survival in many patients. In addition, therapy of ascites alleviates the symptoms and improves the quality of life of the patients, and probably decreases the incidence of life-threatening conditions including spontaneous bacterial peritonitis and hepatorenal syndrome. The mean survival rate at 2 years is approximately 50%. Precipitating factors such as gastrointestinal bleeding, nonsteroidal anti-inflammatory drugs and infections, should be identified, since most of them can be corrected. Most cirrhotics with ascites can be managed with a 'step-by-step' approach, including dietary salt restrictions, aldosterone antagonists, and loop diuretics. When tense or refractory ascites is present, large-volume paracentesis is safe and effective. Peritoneovenous shunting (i.e. Denver, LeVeen) is less frequently used because of perioperative morbidity and mortality, and thrombotic complications with occlusion of the stent. Reinfusion of concentrated ascites is of potential benefit and has been used in Europe. Transjugular intrahepatic portosystemic shunt (TIPS) is an alternative procedure performed by interventional radiologists that allows decompression of portal hypertension. In many cases, ascites is improved after TIPS, but long-term randomized trials for tense or refractory ascites comparing TIPS with standard therapy are not conclusive. Liver transplantation is the ultimate step for the treatment of ascites, providing the cure for the underlying liver disease as well. Transplantation is indicated when quality of life of the patient is impaired due to recurrent episodes of ascites, or in the presence of spontaneous bacterial peritonitis and hepatorenal syndrome.

It has recently been described that kappa-opioid receptor agonists inhibit antidiuretic hormone secretion and promote water excretion in humans and experimental animals. The aim of this study was to evaluate the aquaretic efficacy of the kappa-opioid receptor agonist RU 51599 in conscious cirrhotic rats with ascites and water retention.In protocol 1, arterial pressure, heart rate, and renal water metabolism were measured in basal conditions and then were measured for 120 minutes after the administration of Ringer's solution (n = 8; 0.4 mL) or RU 51599 (n = 7; 1 mg/kg). In protocol 2, plasma antidiuretic hormone concentration was measured (n = 6) before and 60 minutes after administration of RU 51599 (1 mg/kg). In protocol 3, the effect of RU 51599 (n = 9; 1 mg/kg) was compared with that of the V2-receptor antagonist SKF 100398 (n = 9; 30 micrograms/kg).RU 51599 administration induced a profound diuretic and aquaretic effect without altering arterial pressure and heart rate. In protocol 2, the kappa-opioid agonist reduced by about 50% plasma antidiuretic hormone levels (from 6.6 +/- 0.9 to 3.4 +/- 0.6 pg/mL; P0.05). Finally, the improvement in renal water metabolism induced by RU 51599 was similar to that produced by the V2-receptor antagonist.RU 51599 has a potent aquaretic effect in cirrhotic rats with water retention, suggesting that kappa-opioid receptor agonists may be useful for the treatment of water retention and dilutional hyponatremia in cirrhosis.

We measured the plasma levels of atrial natriuretic factor (ANF) during orthotopic liver transplantation (OLT) in eight adult patients with cirrhosis and ascites. The aim of this study was to determine whether significant differences in ANF concentration may be detected during the individual phases of OLT and to correlate these changes with hemodynamics. In each patient a hemodynamic assessment was achieved using a Swan-Ganz fiber optic catheter for continuous monitoring of cardiac output (CO), systemic vascular resistance index (SVRI), right filling pressure as assessed by central venous pressure (CVP), and left filling pressure by means of pulmonary arterial wedge pressure (PAWP). During reperfusion a clear-cut increase in ANF values was observed (P

Here we report the cloning and characterization of a novel cDNA named spata 2. SPATA2 is the ortholog of PD1, a human testicular protein which has been suggested to play a role in spermatogenesis. The spata 2 sequence reveals an open reading frame encoding a protein of 511 amino acids. Northern blot analysis with rat mRNA demonstrated two distinct transcripts of 2.2 and 4.0 kb. Tagging recombinant SPATA2 with the green fluorescent protein (GFP) and expressing the chimeric polypeptide in HLtat transfected cells indicated that SPATA2 is located in the nucleus. RT-PCR analysis revealed that spata 2 mRNA is expressed in the testis and to a lesser extent in the brain while skeletal muscle and kidney showed a barely visible signal. The same analysis demonstrated that isolated Sertoli cells express spata 2 mRNA. Treating Sertoli cells with FSH in vitro induced remarkable changes in the steady-state level of spata 2 mRNA in a time-dependent manner. In developing testis spata 2 transcripts were first detected 10 days post partum and expression levels increased steadily with age. The ability of FSH to stimulate spata 2 mRNA expression as well as its developmental expression suggests that this protein might play a role in regulating spermatogenesis and thus, according to the Gene Nomenclature Committee, we propose the name SPATA2 (Spermatogenesis associated protein 2) for this protein (or gene).