Adenine nucleotide catabolism in the erythrocytes of uraemic patients.
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Biomedical subjects
Publications and source records attributed to B Rutkowski.
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Restriction fragment length polymorphism (RFLP) typing of MHC-class II loci DRB, DQA1, DQB1, DQA2 and DPB1 was performed in 94 patients with seronegative juvenile chronic arthritis (JCA) and 184 random controls. Analysis of allele frequencies and MHC-class II 4-loci haplotypes indicate: (1) Susceptibility to JCA is more strongly associated with the HLA-DQ subregion than with the HLA-DR subregion, especially in early onset pauciarticular JCA (EOPA-JCA). (2) Haplotype and sequence analysis show two independent MHC-class II associations for susceptibility to EOPA-JCA, one located in DQA1, the other in DPB1. (3) Two RFLP defined patterns of the DQA1 locus, DQA1.5 (DQA1*0501) and DQA1.8 (DQA1*0401, *0601) are strongly associated with the disease. (4) Analysis of amino-acid (AA) sequences coded in exon 2 of DQA1 reveals an AA sequence of six AAs common to all three associated DQA1 alleles. This suggests a model that includes a functional role for HLA-DQ molecules in the pathogenesis of JCA.
10 anemic (HB less than 9.0 g/dl) predialysis patients with chronic renal failure were treated for three months with s.c. administration of r-Epo. Blood morphological parameters were estimated using hematological autoanalyser Technicon H1. An increase of the mean hemoglobin (Hb) level from 8.39 to 10.57 g/dl was observed. In 8 patients Hb concentration after 3 months therapy ranged from 9.4 to 12.7 g/dl, but in the remaining two of them Hb was lower than 9.0 g/dl. Appearance of a high percentage of hypochromic erythrocytes is probably the most characteristic response to r-Epo treatment. This phenomenon was caused by iron deficiency. A significant increase of serum creatinine and BUN levels were observed in treated patients, without the concomitant decrease of endogenous creatinine clearance. No clinical symptoms suggesting deterioration of the renal function were observed. Subcutaneous therapy with r-Epo appeared an effective and convenient method of treatment of anemia in predialysis patients.
5 deeply anemic (Hb less than 8 g/dl, Ht less than 25%) dialyzed patients with chronic renal failure were treated during four months with r-Epo. Blood cells morphological parameters were estimated using hematological autoanalyser Technicon H1. Satisfactory increase of the Hb levels and RBC counts were observed in 4 patients, in one the improvement was insignificant. We observed three types of response to r-Epo treatment: 1) macrocytic type, 2) hypochromic type, and 3) non-hypochromic type, without lasting macrocytosis. Our results suggest that type of erythropoiesis depends on other active biological substances (iron, folic acid, vit. B12) necessary for correcting erythropoiesis. r-Epo administration appeared to be a safe and effective method of anaemia treatment in dialyzed patients. Its administration eliminated blood transfusion for six months.
The renal actions of atriopeptin III were compared in sham control, spontaneous and Goldblatt (2-K 1-C) hypertensive rats. Atriopeptin III, administered at 125. 250 and 500 ng/kg or 1.0, 1.5 and 2.0 micrograms/kg, into sham control rats had no effect on blood pressure or renal haemodynamics but caused dose related increases in urine flow, absolute and fractional sodium excretions, from 44 to 248%. Similar excretory responses to this dose range of atriopeptin III were obtained in spontaneously hypertensive rats. Atriopeptin III given at 125, 250 and 500 ng/kg into 2-K 1-C Goldblatt hypertensive rats increased reversibly left kidney urine flow, absolute and fractional sodium excretion by between 55 and 74% which were similar responses to those of sham control left kidneys. By contrast, atriopeptin III had much smaller effects on water and sodium excretions of the right clipped kidneys. These results suggest that atrial natriuretic peptides may be useful in mobilising fluid in genetic hypertension but their usefulness may be restricted in renovascular forms of hypertension.
1. The natriuretic and diuretic effects of atriopeptin III (125, 250 and 500 ng kg-1, i.v.) were studied in groups of rats anaesthetized with pentobarbitone which were either sham controls, unilaterally nephrectomized controls, adenine-fed or subtotal nephrectomy chronic renal failure models. 2. Atriopeptin III given at these doses to the sham control animals had no effect on blood pressure, renal blood flow or glomerular filtration rate but reversibly increased urine flow, between 46% to 54%, absolute sodium excretion, between 52% to 61%, and fractional sodium excretion, between 48% to 54% (all P values less than 0.05) from the lowest to the highest dose. The adenine-fed chronic renal failure group of rats had a reduced renal blood flow of between 30 and 75%, and glomerular filtration rate of approximately 20%, compared to the sham controls. Administration of atriopeptin at 125, 250 and 500 ng kg-1 to the animals with renal failure increased water and sodium excretion to the same degree as observed in the sham group of rats. 3. In the group of unilaterally nephrectomized rats, atriopeptin III, at 125, 250 and 500 ng kg-1 increased urine flow by 36%, 47% and 72%, respectively, absolute sodium excretion by 37%, 57% and 106%, respectively, and fractional sodium excretion by 46%, 45% and 102%, respectively. A similar pattern of responses was observed in the subtotal nephrectomy, chronic renal failure group in which filtration rate was approximately 4 times less than the controls. 4. These results show that in two different models of chronic renal failure, atriopeptin III still caused a natriuresis and diuresis. This suggests that the nephrons retain sensitivity to the atrial natriuretic peptides in diseases such as chronic renal failure and that these compounds may be useful in mobilizing body fluids in this situation.
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Administration of atriopeptin III (125, 250 and 500 ng/kg, intravenously) into pentobarbitone anaesthetized normotensive and DOCA-salt hypertensive rats had no effect on blood pressure or renal haemodynamics. Urine flow and absolute and fractional sodium excretion were increased by 48-90% from the lowest to the highest dose of atriopeptin III in the normotensive group, but were increased by over twice these amounts in the DOCA-salt hypertensive rats. Fractional lithium excretion and calculated proximal tubular fluid reabsorption were unaffected by the peptide in the normotensive rats, but in the hypertensive group atriopeptide III increased fractional lithium excretion by 25-50% and decreased proximal tubular reabsorption to a similar extent. Beyond the proximal tubule there were similar increases in fractional and absolute fluid handling in both groups of rats. These results demonstrated that in DOCA-salt hypertension there was increased sensitivity to the natriuretic activity of atriopeptin III which appeared to result from an increased responsiveness of the proximal tubule.
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