Calcium-phosphate metabolism in patients with multiple sclerosis.

INTRODUCTION AND OBJECTIVES: The purpose of this study was to evaluate the concentration of 25-hydroxycholecalciferol and parameters of calcium-phosphate metabolism at different periods of relapsing-remitting multiple sclerosis (RRMS). MATERIALS AND METHODS: Forty-five patients, residents of Poland (49°-50°, N), were enrolled in the study, i.e. 15 immediately after the diagnosis of RRMS, 15 at the early stage and 15 at the advanced stage of RRMS. The results were compared to values obtained in 20 age- and sex-matched controls. RESULTS: Lower serum concentrations of 25-hydroxycholecalciferol and ionised calcium were found in patients compared to the control group. In patients with the disease duration of 5-6 years, concentrations of 25-hydroxycholecalciferol and ionised calcium were lower than in patients in the earlier period of RRMS. The inverse and clearer direction of changes was found in parathormone serum concentration in patients compared to the controls. In patients with a longer disease duration, a significantly lower 25-hydroxycholecalciferol concentration was found in female patients compared to male patients. In patients, more frequent 25-hydroxycholecalciferol and unsaturated fatty acids' supplementation was observed compared to the controls. CONCLUSIONS: In RRMS patients, calcium-phosphate metabolism is disturbed which increases during disease progression.

Erythrocyte transketolase activity and guanidino compounds in hemodialysis patients.

BACKGROUND: The toxic effects of guanidino compounds on enzymatic activity in uremic patients are known. Thus, we determined the hemodialysis (HD) impact on this toxicity. METHODS: The erythrocyte transketolase activity (ETKA), total guanidino compounds (TGCs), and guanidinosuccinic acid (GSA) levels in plasma were compared before, after 5 hours of HD, and at 12 and 24 hours from the end of HD. Thirty-seven HD patients (28 to 49 years old) with primary glomerulopathies participated in this study. Thirty healthy volunteers (HVs) served as controls. RESULTS: At the beginning of this study, ETKA was lower in uremics (1.94 +/- 0.45) than in HVs (2.59 +/- 0.26). The TGC and GSA plasma levels were higher (26.07 +/- 5.34 and 4.5 +/- 1.22) than in HVs (10.41 +/- 1.42 and 0.76 +/- 0.09, P < 0.001), respectively. After five hours of HD, the ETKA increased to 2.49 +/- 0.62 (P < 0.001). The plasma levels TGC decreased to 12.56 +/- 2.02 (P < 0.001) and the GSA to 2.12 +/- 0.68 (P < 0.001). After 12 and 24 hours from the end of HD, the ETKA decreased to 2.25 +/- 0.56 and 2.09 +/- 0.49 (P < 0.001), respectively. The plasma levels for TGC and GSA both increased: TGC to 19.39 +/- 3.67 and 25.68 +/- 4.61 (P < 0.001), respectively; GSA to 3.49 +/- 1.11 and 4.53 +/- 1.12 (P < 0.001), respectively. CONCLUSION: There was no significant correlation between ETKA and the plasma levels of the examined toxins. By removing the guanidino compounds, HD temporarily decreases the inhibition of ETKA, diminishing other metabolic disturbances connected with pentose phosphate cycle.

[The effect of cocarboxylase treatment on erythrocyte transketolase and blood thiamine in patients with end stage renal disease undergoing maintenance hemodialysis]. / Wplyw leczenia kokarboksylaza na aktywnosc transketolazy w erytrocytach i stezenie tiaminy we krwi u chorych ze schylkowa niewydolnoscia nerek, leczonych powtarzana hemodializa.

The depressed ETKA in ESRD patients is supposed to be caused and/or aggravated by several factors among which the diminished content of thiamine in blood and/or disturbances of thiamine utilization seem to play the major role. This role stems from the fact that thiamine acts as the cofactor of transketolase. In order to check the therapeutic significance of this relationship we introduced the thiamine pyrophosphoric acid ester chloride (Cocarboxylasum-CC) administration in 25 patients (mHD + CC). Immediately after each HD performance CC was given i.v. during 12 weeks in a doses of 5 mg/kg b.w., 3 times a week. The blood for ETKA value, free and total thiamine in plasma and erythrocytes, as well as, the total protein and albumins/globulins index investigation was drawn before, after 6 and 12 weeks of CC administration, and 3 months after cessation of this therapy. In 10 patients, on maintenance HD nontreated by CC (mHD), the blood was drawn at the same time intervals. Normal values we obtained from 15 healthy volunteers. For ETKA evaluation photocolorimetric method was used, thiamine content in blood was estimated by fluorimetric method. At the beginning of the study the mean value of ETKA, in two examined groups, was found statistically decreased (p < 0.01) when compared with normals. Mean values of thiamine in plasma and erythrocytes were lower but did not differ significantly from those in normals. After 6 weeks of CC administration ETKA value increased, but only after 12 weeks it increased significantly (p < 0.01), reaching normal value. On the other hand, striking increase in plasma thiamine and erythrocyte thiamine levels was observed after 6 weeks of CC administration already (p < 0.01). Three months after cessation of CC administration significant decrease in ETKA value and thiamine level in blood was observed (p < 0.01). ETKA returned to lower value than in normals even in the presence of still high thiamine levels in blood. In mHD patients nontreated by CC the ETKA value and thiamine levels in blood did not change significantly during all periods of study. The nutritional status assessed by total protein and albumins/globulins index did not change in both groups through the study. We conclude, the administration of high doses of CC to ESRD patients on maintenance hemodialysis HD was successful in terms of increasing ETKA value and thiamine levels in blood without any side effects. Thus, supplementation with large doses of CC deserves further study because it promises to be another adjunct in the treatment of potential thiamine deficiency and metabolic disturbances in the course of dialysotherapy.

Comparison of the thiamine level in blood and erythrocyte transketolase activity in hemodialyzed and nondialyzed patients during recombinant human erythropoietin therapy.

Thiamine and erythrocyte transketolase activity (ETKA) disturbances in end-stage renal disease are caused mainly by uremia and dialysis treatment. We examined whether recombinant human erythropoietin (rhEPO) can correct these abnormalities in uremic patients. Thirteen hemodialysis (HD) and 12 nondialyzed (ND) anemic patients showed decreased free and total thiamine levels in plasma and in erythrocytes and decreased ETKA when compared to 20 healthy subjects. Thiamine blood levels (mumol/l) were determined using a fluorimetric technique, and ETKA (mumol/l per minute) was assessed with a photocolorimetric method. Over 20 weeks of study, rhEPO was given intravenously for 8 weeks at 50 Ul/kg body weight (BW) three times a week, and subcutaneously for 4 weeks at 25 Ul/kg BW, twice a week, and for the last 8 weeks at 25 Ul/kg BW once a week. The correction of anemia was associated with an increase in plasma thiamine and erythrocyte total thiamine as well as ETKA in HD patients and with an increase in erythrocyte total thiamine in ND patients only during the period of intravenous infusions.

Recombinant human erythropoietin improves enzyme activity in erythrocytes of predialysis uremics.

The influence of r-HuEPO on the activity of erythrocyte transketolase (ETKA), glutathione reductase (GSH) and glutamic-pyruvic transaminase (EGPT) was determined by spectrophotometry. 150 IU/kg BW/week of r-HuEPO was given i.v. during 2 months to 12 predialyzed uremics (PDU). Twenty healthy volunteers (HV) served as controls. GSH and EGPT activity were expressed as a coefficient. ETKA in HV = 2.39 +/- 0.10 and PDU = 1.53 +/- 0.10 mumol/ml/min differed significantly (p < 0.001). GSH in HV = 1.20 +/- 0.09 and PDU = 1.25 +/- 0.07, EGPT in HV = 1.20 +/- 0.10 and PDU = 1.38 +/- 0.11 differed significantly (p < 0.01 and p < 0.001, respectively). After 2 months of r-HuEPO treatment, ETKA, GSH and EGPT rose significantly (p < 0.01). Thus, r-HuEPO increases the activity of enzymes related with the content of vitamins B1, B2 and B6 in uremics.

[Uremic polyneuropathy in patients treated conservatively (nondialyzed) or treated with dialysis]. / Polineuropatia mocznicowa u chorych leczonych zachowawczo (niedializowanych) lub leczonych dializami.

Uremic polyneuropathy is a common complication in dialyzed patients (pts). In 37 end stage renal disease (ESRD) pts the electroneurophysiological (ENF) parameters and serum creatinine (Pcr), guanidino compounds (GC) and guanidinosuccinic acid (GSA) levels were studied. There were 21 nondialyzed (ND), 10-hemodialyzed (HD) and 6-intermittently peritoneally dialyzed (IPD) pts. The following ENF parameters on both upper extremities, using method described by Buchtal and Rosenfalck, were performed: sensory nerves (nn.) conduction velocity, amplitude of evoked potential, subjective and objective impulse and motor nerve-conduction velocity. Cr level in serum was measured by enzymatic method, GC-by Rosenberg, Ennor, Morison method, modified by Szczepkowska. GSA isolation was performed by column chromatography. The results indicated disturbances in peripheral nn. function in all studied groups of pts and did not correlate with levels of uremic toxins in serum. However, it does not mean, that sum of the accumulated various toxic metabolites in ESRD pts, does not influence the development of polyneuropathy. The degree of impairment of peripheral nn. conduction in ESRD did not differ significantly between ND and HD or IPD pts. We did not notice, any significant differences in the degree of polyneuropathy in HD or IPD pts.

[Content of thiamin in plasma and erythrocytes in patients with end stage renal disease]. / Zawartosc tiaminy w osoczu i erytrocytach u chorych ze schylkowa niewydolnoscia nerek.

In 68 patients with end stage renal disease (ESRD), nondialyzed-(ND)-21 treated by hemodialysis (HD)-27 or intermittent peritoneal dialysis (IPD)8 and continuous ambulatory peritoneal dialysis (CAPD)-12, we examined thiamine free (Th F) and thiamine total (Th T) content in plasma (P) and erythrocytes (E). 20 healthy volunteers (HV) served as a control group. Thiamine content in plasma and in hemolysate was assessed by fluorimetric method according to Blum and Merkel. In all patients the mean Th FP, Th TP, and Th FE, Th TE levels were decreased in comparison to HV. Mean level of Th FE in ND and IPD was significantly decreased (p < 0.05) in comparison to Th FE to HV and to patients treated by HD or CAPD. Mean level of Th FP was the lowest in IPD group, but did not differ significantly from Th FP in ND, HD and CAPD). In IPD patients mean level of Th TE was the lowest and differed significantly (p < 0.05) from that in HD and CAPD groups. The lowest mean level of Th TP we found in CAPD patients. There was significant difference with it in ND and HV group (p). Patients treated by HD and CAPD presented almost normal levels of Th FE and Th TE. The highest mean levels of Th FP and Th TP were found in ND patients. We suggest the need of thiamine supplementation in ESRD patients especially in those treated by dialysis. The supplementation of thiamine is needed particularly in patients on peritoneal dialysis.

[The influence of intermittent peritoneal dialysis on free and total thiamine concentration in plasma and erythrocytes of patients with end stage renal disease]. / Wplyw przerywanej dializy otrzewnowej na stezenie tiaminy wolnej i calkowitej w osoczu i erytrocytach u chorych ze schylkowa niewydolnoscia nerek.

The concentration of free and total thiamine in plasma (PFTh and PTTh) and in erythrocytes (EFTh and ETTh) was determined in 20 healthy volunteers and in 8 patients suffering from ESRD treated (60 hrs/week) with IPD. Venous blood for determinations was taken immediately before and at the end of the subsequent 20-hrs PD as well as, after 12 and 48 hrs elapsed from the completion of this procedure. Thiamine was determined using fluorimetric method. Mean concentration of PFTH and PTTh as well as ETTh of patients before dialysis was found to be low, but did not differ significantly from those found in the group of healthy volunteers. Mean value of EFTh before PD was statistically lower than in normals (p < 0.05). After dialysis lasting 20 hrs a significant lowering of the concentration of PFTH (p < 0.001) and PTTh (p < 0.01) has been observed, whereas the concentration of EFTh and ETTh significantly increased (p < 0.05). After 12 and 48 hrs elapsed from the completion of dialysis a statistically significant increase in PFTh and PTTh concentration has been noted contrasting with those in EFTh and ETTh, where it felt down. Nevertheless these values in plasma and erythrocytes after 48 hrs from the completion of dialysis did not differ significantly from those found at the beginning of the determination. We conclude that IPD is a procedure exerting short-term lowering of the plasma thiamine concentration with simultaneous increase in those in erythrocytes concentration. Further studies are indispensable to clarify the problem of thiamine supplementation in patients treated with PD.

Recombinant human erythropoietin administration improves thiamine content in blood and erythrocytes transketolase activity in pre-dialyzed patients.

Recombinant human erythropoietin (r-Hu EPO) has proved to be effective in correcting anemia of dialyzed patients. Since 1987 reports have been published announcing the introduction of this hormone to the treatment of anemia in pre-dialyzed patients, too. Besides successful correction of anemia no evidence of acceleration of the progression of renal failure has been noted. The question of whether r-Hu EPO can also correct metabolic disturbances in predialyzed patients is to be answered. These metabolic disturbances comprises, among others, the decrease in thiamine content in blood and the deterioration of erythrocytes transketolase activity (ETKA) we described in another paper. However, as to the present we did not notice any publication concerning the impact, of r-Hu EPO administration on thiamine content in blood and on the ETKA. The purpose of our study was therefore to determine the influence of r-Hu EPO therapy in pre-dialyzed patients on thiamine level in plasma and erythrocytes and on the ETKA. Additionally, we wanted to answer the question if there was any parallel change in hematocrit index, thiamine level in blood and the ETKA in patients we observed during r-Hu EPO therapy.

[Effect of methylguanidine and guanidinosuccinic acid on pyruvate kinase activity in human red cells]. / Wplyw metyloguanidyny i kwasu guanidynobursztynowego na aktywnosc kinazy pirogronianowej krwinek czerwonych czlowieka.

An effect of methylguanidine and guanidinosuccinic acid on pyruvate kinase activity in human red cells was determined in vitro following a 3-hour incubation at 37 degrees C. The obtained results have shown that methylguanidine in the concentration of 1.8 x 10(-5) M/l inhibits pyruvate kinase activity by 20.8%. Pyruvate kinase activity was statistically significantly inhibited on addition of methylguanidine in the concentration of 5.4 x 10(-5) M/l whereas higher concentrations have no such an effect Guanidinesuccinic acid exerted similar but weaker effect on the activity of pyruvate kinase in human red cells. Mixture of methylguanidine (5.4 x 10(-5) m/l) and guanidinesuccinic acid (2.8 x 10(-5) M/l) does not affect pyruvate kinase activity in normal human red cells under identical experimental conditions.

[Evaluation of the capacity of the liver for phenazone biotransformation in patients with uremia on peritoneal dialysis]. / Ocena zdolnosci watroby do biotransformacji fenazonu u dializowanych otrzewnowo chorych na mocznice.

This work aimed at establishing whether liver ability to biotransformation of drugs expressed by antipyrine kinetics is disturbed in peritoneally dialysed patients with end-stage renal failure. The investigations were carried out in 10 uraemic patients using the antipyrine test and comparing antipyrine kinetics with those obtained in 13 healthy individuals. At the time of investigations, standard clinical tests of liver function were normal and HBs antigen was absent in all patients. It was shown that peritoneally dialysed patients with end-stage renal failure had not significantly changed antipyrine elimination as compared with the group of healthy controls: t0.5 = 13.2 +/- 6.8 v. 11.8 +/- 8.1 h, plasma clearance = 50 +/- 30 v. 34 +/- 21 ml/min (x +/- SD). The obtained results indicate that antipyrine kinetics is within normal range in uraemic patients regularly dialysed suggesting cytochrome P-450 in microsomes not being markedly reduced.

Assessment of liver ability to biotransformation of antipyrine in uraemic patients on regular peritoneal dialysis treatment.

It was the aim of this work to establish whether biotransformation of drugs by the liver expressed by antipyrine kinetics is disturbed in peritoneally dialysed patients with end-stage renal failure. The investigations were carried out in 10 uraemic patients using the antipyrine test and comparing the parameters of antipyrine kinetics with those obtained in 13 healthy persons. Our results indicate that in uraemic patients on regular peritoneal dialysis treatment antipyrine kinetics are generally in the normal range, suggesting the microsomal content of cytochrome P-450 being not evidently reduced.

Intravascular degranulation of polymorphonuclear neutrophils during hemodialysis. The effects of pretreatment with colchicine.

Polymorphonuclear neutrophil (PMN) counts, plasma activity inducing PMN aggregation, augmenting PMN adherence and chemotactic activity were estimated during hemodialysis (HD) with cuprophane membranes. All these plasma activities are accepted as related to the presence of activated complement (C). The same estimations were made for hemodialyzed patients pretreated with colchicine. The results, especially comparison of plasma activities in blood entering and leaving the dialyzer, indicate that significant amounts of activated C components are generated within the patients vascular bed. The PMN entrapped in the pulmonary microcirculation that undergo subsequent degranulation are most probably the source of these C components. This concept was confirmed by the results for patients pretreated with colchicine, who had significantly less of the activities generated in the patients own circulation.

Phagocytosis and neutrophil bactericidal capacity in patients with uremia.

The phagocytic activity and bactericidal capacity of polymorphonuclear neutrophils (PMN) were evaluated in patients with advanced chronic renal failure. The studies were made in patients undergoing hemodialysis, maintenance peritoneal dialysis as well as in nondialysed patients. Evaluations were carried out by using of the recently described fluorochrome microassay which enabled these parameters to be estimate independently. The phagocytic activity was seriously diminished in nondialysed patients, whereas it was similar to controls in those hemodialysed and undergoing peritoneal dialysis patients. In all evaluated groups of patients the bactericidal capacity was significantly reduced. The lowest values could always be observed in nondialysed patients. The decrease of bactericidal capacity was significantly more evident in patients undergoing peritoneal dialysis as compared with those hemodialysed. The obtained results confirm some previous reports suggesting the impairment of PMN function in uremic patients. This results in their increased susceptibility to infection. They also reveal the existence of a close relationship between the extent of observed dysfunctions and the management applied.

Influence of hemodialysis on plasma chemotactic activity and the chemotactic responsiveness of polymorphonuclear neutrophils.

Thirty patients with chronic renal failure on maintenance hemodialysis (HD) were studied. Plasma chemotactic activity was estimated using the "under agarose" chemotaxis assay during the first 2 h of HD. It was found that in the fifth minute of HD, patients' plasma became chemotactic, reaching the maximum activity at the tenth minute. The chemotactic activity appearance correlated significantly with the decline in the number of the peripheral neutrophils. Patients' neutrophils, after a single passage through the cellophane coil of the dialyzer, revealed significant impairment of directed migration toward both complementary and bacterial chemoattractants. Moreover, the chemotactic properties of neutrophils obtained from dialyzed patients before HD were significantly lower than had been estimated in 15 nondialyzed patients with chronic renal failure. The results confirm HD-induced complement activation and might explain the mechanisms of the increased susceptibility of dialyzed patients to bacterial infections.