Dietary L-aspartate and L-glutamate inhibit fatty streak initiation in cholesterol-fed rabbit.

BACKGROUND AND AIM: Low-density lipoprotein (LDL) oxidation is a potential atherogenic agent, and protecting LDL from oxidation prevents atherogenesis. It has been shown that L-aspartate and L-glutamate decrease lipid peroxidation after reoxygenation by means of the initiation of the cardiopulmonary bypass circuit (CPB), when supplemented to the CPB prime, and so they may protect against atherogenesis. The aim of this study was to evaluate the effect of the dietary administration of L-aspartate and L-glutamate on fatty streak onset in cholesterol-fed rabbit. METHODS AND RESULTS: Male New Zealand white rabbits were fed for four weeks with either a high-cholesterol plus corn oil diet (control group) or the same diet supplemented with 12.5 mM L-aspartate and 12.5 mM L-glutamate in drinking water (Asp + Glu group). The mononuclear cells adhering to the endothelium and the intimal foam cells of the thoracic aorta were used to quantify the extent of atherosclerosis. Total serum cholesterol and lipid peroxidation activity, measured as thiobarbituric acid reactive substances (TBARS), were determined 0, 1 and 4 weeks after a 2-week adaptation period. There were no between-group differences in body weight or food intake during the intervention. Serum TBARS were significantly increased in both groups during the experimental period but without any statistical difference between groups. At the end of the dietary intervention, there was a ten-fold increase in total serum cholesterol concentration in both groups vs baseline. The numbers of adherent mononuclear cells and intimal foam cells were both significantly lower in the Asp + Glu group. CONCLUSIONS: Our results suggest that dietary supplementation with L-aspartate and L-glutamate seems to protect the arterial wall from atherogenesis in an experimental animal.

On the usefulness of glycylglycine in hemodialysis and peritoneal dialysis solutions.

This article reviews current knowledge on the usefulness of glycylglycine in preparing single stable hemodialysis (HD) and peritoneal dialysis (PD) solutions containing bicarbonate. The coexistence of bicarbonate and glycylglycine in a dialysis solution renders it a potent, stable buffer in which the well known reactions between bicarbonate and calcium and magnesium, and the subsequent formation of insoluble neutral calcium and magnesium carbonate salts, are avoided. Single stable bicarbonate-glycylglycine (BiGG) solutions for HD and PD have been successfully prepared and studied, both experimentally and clinically. These studies have demonstrated the advantages of BiGG solutions in terms of simplicity, stability, convenience, tolerance, biocompatibility, protection of the peritoneum, and higher ultrafiltration, compared to standard acetate or lactate solutions, and on-line prepared bicarbonate solutions. Progressive accumulation of glycylglycine or glycine, even after prolonged use, side effects, or signs of toxicity were not observed. In conclusion, BiGG solutions ensure a physiologic dialysis both from the theoretic and practical points of view.

In vitro effects of bicarbonate- versus lactate-buffered continuous ambulatory peritoneal dialysis fluids on peritoneal macrophage function.

At present, lactate is the most commonly used buffer in peritoneal dialysis fluids (PDFs). The high lactate concentration in combination with low original pH was demonstrated to suppress phagocytic function. We evaluated the in vitro effects of a newly formulated bicarbonate-buffered PDF containing glycylglycine (BiGG15 and BiGG40; Pierre Fabre Medicament, Castres, France) on peritoneal macrophage (PMO) function, and compared them with those of equiosmolar lactate-buffered PDF (1.5% and 4.25% glucose; pH 5.4 and pH 7.4) and control buffer. Peritoneal macrophages were isolated from the effluents of 10 continuous ambulatory peritoneal dialysis patients and tested for luminol- and lucigenin-enhanced chemiluminescence, superoxide (O2-) generation measured by cytochrome c reduction, killing capacity, and phagocytosis after incubation in the PDF used. Exposure of PMO to lactate-buffered PDF with an original pH of 5.4 resulted in a significant suppression of all PMO functions measured, compared with bicarbonate- and lactate-buffered PDFs with a pH of 7.4. At physiological pH (7.4), chemiluminescence generation of PMO exposed to BiGG15/40 was significantly higher compared with the corresponding equiosmolar lactate-buffered PDF (1,992 +/- 858 x 10(3) cpm/10(4) cells v 856 +/- 398 x 10(3) cpm/10(4) cells; P < 0.004). O2- generation, killing capacity, and phagocytosis were not significantly different after PMO exposure to bicarbonate compared with exposure to lactate-buffered PDF with a neutral pH. Irrespective of the buffer used, high-osmolality PDFs suppressed PMO function significantly more than low-osmolar PDFs. In conclusion, bicarbonate-buffered PDFs are less detrimental to PMO function than lactate-containing PDFs; these preliminary in vitro results need to be confirmed in vivo.

Effects on the peritoneal membrane of rabbits of a single bicarbonate solution containing glycylglycine.

So far, no one has devised ideal, on-line mixed bicarbonate solutions for hemodialysis and continuous ambulatory peritoneal dialysis (CAPD) because current preparations can lead to precipitation of calcium and magnesium carbonate during treatment. The author has prepared a new, single bicarbonate dialysis solution that contains glycylglycine (BiGG). With a bicarbonate/glycylglycine ratio of 30/10 mM/L, this solution has a stable pH of 7.35; sterilized through a 0.22 micron filter, it remains stable for over 15 months when stored at 10 degrees-40 degrees C. When infused (40 mL/kg bw) in rabbits daily for 25 days, the BiGG solution showed excellent peritoneal-membrane tolerance and biocompatibility. Comparative ultrafiltration (UF) studies with BiGG and standard lactate (La) solutions in rabbits showed that net UF with La solution peaked at 2 h and decreased significantly at 4 h and 6 h. Net UF with BiGG solution peaked at 4 h and was sustained at 6 h; in all instance it was greater than that of La solution by approximately 15%, 30%, and 40% at 2, 4, and 6 h, respectively. During the initial 2-h dwell period, the pH of La solution increased from an initial 5.5 to 7.18, whereas that of the BiGG solution remained stable at 7.35. In all rabbits, the peritoneal fluid contained phosphatidylcholine at all times. However, its concentration was significantly higher in animals receiving the BiGG solution than in those receiving the La solution. The author concludes that this new single BiGG PD solution is simple to use, stable, and of a normal pH.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodialysis with a new single stable bicarbonate dialysate.

A specified stable bicarbonate/glycylglycine dialysate for hemodialysis (HD) analogous to those introduced by us for continuous ambulatory peritoneal dialysis (CAPD) is described. HD with this single dialysate is simple, easy, safe and of reasonable cost. Results obtained from 6 HD patients proved its superiority against acetate dialysate. Bicarbonate/glycylglycine dialysate is also more stable, harmless and easier to use than bicarbonate dialysate prepared on-line.

Enhanced ultrafiltration in rabbits with bicarbonate glycylglycine peritoneal dialysis solution.

OBJECTIVE: The aim of the study was to investigate net ultrafiltration (NUF) with a new bicarbonate glycylglycine (BiGG) peritoneal dialysis solution compared to the standard lactate (La) solution. DESIGN: In six groups of 12 normal rabbits each we measured NUF after a 2-, 4-, and 6-hour peritoneal dialysis with a BiGG solution (pH 7.35) and a standard La solution (pH 5.5) of similar glucose, electrolyte, and osmolality formulation. Furthermore, we studied the phosphatidylcholine concentration in the effluent of the two solutions. RESULTS: NUF volume was significantly greater with the BiGG rather than with the La solution by approximately 15% (p < 0.05), 30% (p < 0.01), and 40% (p < 0.005) at 2, 4, and 6 hours, respectively. The glucose absorption rate was greater with the La solution than with the BiGG solution, but the difference was significant only at 2 hours (p < 0.05). pH was increased in the La solution from its initial value of 5.5 to 7.18, 7.32, and 7.40 at 2, 4 and 6 hours, respectively, while it remained almost unchanged in the BiGG solution. Phosphatidylcholine (PC) in the peritoneal effluent was significantly higher in the BiGG solution in all instances (p < 0.0001). CONCLUSION: It is concluded that the BiGG solution, which has a stable pH, 7.35, due to the potent buffering capacity of bicarbonate and glycylglycine, enhances peritoneal NUF by maintaining a higher osmotic gradient and retarding lymphatic absorption through an increase in PC concentration in the peritoneal cavity.

Combined recombinant human erythropoietin-blood letting strategy for treating anemia and iron overload in hemodialysis patients.

We studied the feasibility of treating refractory anemia and post-transfusional serious hemochromatosis in a patient undergoing hemodialysis (3x4 h weekly) for fourteen years, with recombinant human erythropoietin (r-HuEPO) associated with blood-letting. Blood transfusion previously received by the patient at a rate of two units of packed red cells every month for nine years was stopped and r-HuEPO (80 U/kg b.w.) was administered i.v. at the end of each hemodialysis. When Hct increased over 30%, approximately 40 ml of blood was removed per hemodialysis session in an attempt to accelerate iron loss. Excellent control of anemia and hemochromatosis was achieved after seven months of treatment. The patient's general condition and skin pigmentation were significantly improved.

Restoration by biotin of the in vitro microtubule formation inhibited by uremic toxins.

Tubulin is an intracellular protein whose in vivo polymerization leads to the formation of microtubules (MT). MT are essential component of axons of nerve cells. This reaction is the limiting factor in the growth of axons. Uremic neuropathy is characterized in part by an axonal degeneration. A chromatographic fraction from uremic plasma (2-5 fraction) inhibits in vitro the tubulin polymerization and thus MT formation and therefore may be implicated in the occurrence of uremic neuropathy. In vitro, biotin counteracts the inhibitory effect of 2-5 fraction on MT formation. This effect could be a partial explanation of the possible clinical improvement brought on by biotin in uremic neuropathy.

A new stable bicarbonate dialysis solution for peritoneal dialysis: preliminary report.

This paper describes the use of glycylglycine to prepare dialysis solution containing bicarbonate, calcium and magnesium. Bicarbonate with glycylglycine form a buffer with a constant pH of 7.35, which prevents reaction with calcium or magnesium and the formation of insoluble carbonate salts. This bicarbonate-based solution is stable over long periods and can be used with the same simplicity and convenience as lactate solution for peritoneal dialysis (PD) in humans.

Structural changes and variations of uric acid in normal pregnancy.

Fifteen normal pregnant women were studied. Serial measurements of serum total, free and bound uric acid and their clearances were done in early (10-20 weeks), mid- (20-30 weeks) and advanced (30-40 weeks) pregnancy, and after delivery (4-5 weeks). The following was observed. 1. A decrease in early and mid-pregnancy of total and free uric acid (p less than 0.001). 2. A gradual increase from the early to advanced pregnancy of bound uric acid (p less than 0.001). 3. An increase in early and mid-pregnancy of total uric acid clearance and a similar but more pronounced increase of free uric acid clearance (p less than 0.001). These findings explain many differences in previous conflicting reports concerning the metabolic behavior of uric acid, and place future investigation thereof on a more promising basis in normal and abnormal pregnancy.

Re-evaluation of ascorbic acid deficiency in hemodialysed patients.

In 92 uremic patients under chronic hemodialysis without ascorbic acid supplementation, serum ascorbic acid was measured before hemodialysis and between two sessions. The results indicated a more serious ascorbic acid deficiency of patients than in previous studies. This difference might be explained by the highly specific enzymatic method applied in the present study, excluding any potential interference of various serum reducing substances.

Serum ferroxidase I and II in uremic patients under conservative treatment and maintenance hemodialysis.

Serum ferroxidase I (ceruloplasmin) and ferroxidase II activities were studied in 49 uremic patients under conservative treatment, in 79 patients undergoing hemodialysis and in 56 healthy subjects, as controls. Ferroxidase I was significantly higher in both groups of patients. Ferroxidase II was significantly elevated only in patients undergoing chronic hemodialysis. The cause of this difference is not clear, but seems to be of considerable interest.

Successful sodium thiosulphate treatment for recurrent calcium urolithiasis.

Thirty-four idiopathic rapid calcium stone formers (24 male/10 female) were studied. Their ages ranged from 20 to 60 years (40 +/- 11) and all had good renal function. The trial comprised two consecutive periods of 3 years and 4 years duration respectively. In the first (control period), the patients were maintained on a customary diet with an adequate fluid intake sufficient to produce about 2 liters of urine daily. In the second (treatment period), they received a similar diet plus 20 mmol of sodium thiosulphate daily. New stone development fell from 100 in the control period to 15 in the treatment period, corresponding to a rate of 0.98 and 0.11 per year (p less than 0.001). It is suggested that the benefit from sodium thiosulphate results from calcium thiosulphate formation in urine, a salt with a molar solubility of 250 to 100.000-fold greater than that of other urinary calcium salts.

Biotin in the management of uremic neurologic disorders.

In 9 patients undergoing chronic hemodialysis for 2-10 years and suffering from encephalopathy (dialysis dementia) and peripheral neuropathy, 10 mg of biotin was given daily in three doses for 1-4 years. Within 3 months there was a marked improvement in all patients in respect to disorientation, speech disorders, memory failure, myoclonic jerks, flapping tremor, restless legs, paresthesia and difficulties in walking. It is recommended to start giving biotin regularly in any patient with advanced renal failure before severe neural or muscular lesions become manifest. The correlation of biotin with uremic neurologic disorders and the possible mechanism of its therapeutic action are discussed.