Serum fibroblast growth factor 21 is predictive of combined cardiovascular morbidity and mortality in patients with type 2 diabetes at a relatively short-term follow-up.

AIMS: We hypothesised that serum fibroblast growth factor 21 (FGF-21), a novel adipokine with postulated insulin-sensitizing effects, may be predictive of cardiovascular (CV) events in patients with type 2 diabetes (DM2) at a relatively short-term follow-up. METHODS: Serum FGF-21 levels were assessed in 87 DM2 patients, aged 57-66 years, with the median duration of diabetes of 10 years, who were referred to the Department of Endocrinology for routine annual metabolic assessment. During a follow-up of 24 months, overall mortality, CV mortality and CV nonfatal events were registered. Cox proportional hazards regression assessed adjusted differences in CV morbidity and mortality risk. RESULTS: Patients stratified according to serum FGF-21 levels ≤ and > the median value of 240.7 pg/mL showed no significant differences at baseline in gender distribution, diabetes duration, insulin therapy, BMI, biochemical profiles and previous CV events. At 24-month follow-up, 21 (24.1%) patients experienced a nonfatal CV event. A significantly (P=0.0013) higher incidence of the combined end point of CV morbidity and mortality was observed in the FGF-21>240.7 pg/mL group. In the multivariate Cox proportional hazards regression model, the presence of FGF-21>the median value was associated with a significant increase in the risk of the combined end point of CV morbidity and mortality (HR: 4.7, 95% CI 1.67-13.24). CONCLUSIONS: The obtained results support the prognostic value of FGF-21 in DM2 and may provide a useful tool for stratification of CV prognosis in DM2 patients.

Effect of parenteral cladribine on relapse rates in patients with relapsing forms of multiple sclerosis: results of a 2-year, double-blind, placebo-controlled, crossover study.

OBJECTIVE: This randomized, 2-year, double-blind, placebo-controlled, crossover study evaluated cladribine for relapsing forms of multiple sclerosis. PATIENTS: (n = 84) received seven 5-day courses of subcutaneous cladribine at 5 mg/day (group A) or placebo (group B) in year 1; treatment was reversed in year 2. RESULTS: Cladribine was well tolerated and associated with a favorable safety profile. Mean Expanded Disability Status Scale scores remained stable. In group A, mean relapse rates were 0.15 in year 1 (cladribine) and 0.42 in year 2. In group B, relapse rates were 0.61 in year 1 and 0.50 in year 2 (cladribine). PATIENTS required fewer steroid courses during cladribine periods. The therapeutic efficacy of cladribine was associated with a sustained reduction in lymphocyte count.

Effect of riluzole (Rilutek) treatment on plasma amino acid percentages in amyotrophic lateral sclerosis patients.

The aim of the study was to investigate the effect of riluzole (Rilutek) treatment on plasma amino acids (AA) percentage capacity in amyotrophic lateral sclerosis (ALS) patients. Excitatory AA may be important in the pathogenesis of ALS. Riluzole is a neuroprotective drug that blocks glutamatergic neurotransmission in the central nervous system. The study was conducted at the Department of Neurology, University School of Medicine in Lublin. The study comprised 20 ALS patients. Plasma AA were measured by automated ion-exchange chromatography before and after 3 months of riluzole treatment. The study has shown a significant decrease in serine percentage capacity and a significant increase in isoleucine percentage capacity in the plasma of the ALS patients, however the plasma excitatory AA percentage capacity was not significantly changed after 3 months of the riluzole treatment. Our investigations revealed that riluzole does not significantly influence the majority of plasma AA percentage capacity in ALS patients.

Plasma amino acids percentages in amyotrophic lateral sclerosis patients.

The aim of the study was to examine plasma amino acids (AA) percentages in amyotrophic lateral sclerosis (ALS) patients. Altered metabolism of AA, especially excitatory AA in ALS, has been reported. The investigation was conducted at the Department of Neurology, University School of Medicine in Lublin. The study comprised 50 patients; 20 persons with ALS and 30 controls. Plasma AA were measured by automated ion-exchange chromatography. The results show significantly lower percentages of plasma tyrosine, valine, methionine, leucine, and isoleucine and significantly higher percentages of plasma glutamine and serine in ALS than in controls. The clinical state significantly influenced the percentage of plasma phenylalanine and alanine. Our study shows significant changes in some plasma AA percentages in ALS; however, excitatory AA percentages did not differ from the control subjects.

Plasma amino acids concentration in amyotrophic lateral sclerosis patients.

Previous investigations showed an impairment of amino acids (AA) metabolism in amyotrophic lateral sclerosis (ALS). It was hypothesized that excitatory AA may play an important role in the etiopathogenesis of this disease. The aim of the study was to determine plasma AA concentrations in ALS patients, and to examine the relationship between AA and the clinical state of ALS patients, the type of ALS onset and the duration of the disease. The study involved 20 ALS patients and 30 control group people. The AA analysis was performed by ion - exchange chromatography on an automatic AA analyser. The results showed significantly decreased concentrations of valine, isoleucine, leucine, tyrosine and aspartate in the plasma of the whole group of ALS patients compared to the control group, and a significantly decreased concentration of arginine in the patients with a long duration of ALS compared to the patients with a short duration. The clinical state of ALS patients significantly influenced only plasma alanine concentration. Other plasma AA concentrations were not significantly associated with clinical parameters of the disease. Our study confirms that metabolic abnormalities concerning AA exist in ALS patients. However, the normal plasma glutamate concentration observed in this study in the whole group of ALS patients compared to the controls does not exclude that this excitatory AA may play a role in neurodegeneration in ALS.

Concentration of Lp(a) and other apolipoproteins in predialysis, hemodialysis, chronic ambulatory peritoneal dialysis and post-transplant patients.

Serum levels of lipids, lipoprotein(a) Lp(a) and other apolipoproteins were determined in 47 predialysis patients, 40 hemodialysis (HD) patients, 39 chronic ambulatory peritoneal dialysis (CAPD) patients, 11 patients after kidney transplantation and 47 healthy subjects as reference group. The predialysis, HD, and CAPD patients had disturbances in the concentration of serum triglyceride (TG), high density lipoprotein (HDL)-cholesterol, apolipoprotein AI (apoAI), total apoCIII, apoCIII present in the particles without apoB (apoCIII non B), and Lp(a) and HDL-cholesterol, low density lipoprotein (LDL)-cholesterol/HDL-cholesterol, HDL-cholesterol/apoAI, apoAI/apoB, and apoAI/apoCIII ratios. Predialysis patients had significantly lower concentrations of HDL-cholesterol and total apoE levels than CAPD patients and total apoE level than HD patients. Moreover, both HD and CAPD patients had significantly increased levels of apoB containing apoE (apoB:E) and apoB containing apoCIII (apoB:CIII). The concentrations of serum TG, total cholesterol, LDL-cholesterol, apoB, Lp(a) in CAPD patients were statistically higher than in HD patients. The patients after transplantation demonstrated normalization of lipid and lipoprotein parameters and lipoprotein ratios except serum levels of TG, total apoCIII, apoCIII non B and the apoAI/apoCIII ratio. We concluded that abnormal lipid and lipoprotein concentrations in patients with uremia may be the cause of their high risk of atherosclerosis, but posttransplant patients exhibited improved levels of serum lipids, Lp(a) and other lipoprotein parameters and lipoprotein composition, which could be an index of decreased atherogenic status.

Lipoprotein profiles at different stages of chronic renal insufficiency.

BACKGROUND: Lipoprotein abnormalities characteristic of renal dyslipoproteinemia are significantly associated with different stages of chronic renal insufficiency. The renal dyslipoproteinemia may contribute not only to accelerated development of atherosclerosis but also to progression of human chronic renal insufficiency. METHODS: The purpose of the studies was to estimate the lipid and lipoprotein profiles in 52 not dialysed patients with various renal insufficiency advancement. Basing on creatinine level the patients were divided into 3 groups. CR1-A--serum creatinine 2-5 mg/dL (n = 16), CR1-B--serum creatinine 5-10 mg/dL (n = 19), CR1-C--serum creatinine > 10 mg/dL (n = 17). RESULTS: In CR1-A and CR1-B dyslipoproteinemia was found at different stages of renal insufficiency which was manifested by the significant increase of TG, TC, LDL-C, apo B levels and TC/HDL-C, LDL-C/HDL-C ratios and significant decrease of HDL-C level and apo AI/apoB, HDL-C/apoAI ratios in comparison with controls. We also observed decreased TG, TC, LDL-C, apo AI, apo B levels and TC/HDL-C, LDL-C/HDL-C ratios and unchanged HDL-C level and apo AI/apoB, HDL-C/apoAI ratios in cm-c in comparison to CR1-A. The decrease of the lipoprotein parameters in CR1-C might result from malnutrition (statistically decreased albumin level) and metabolism disturbances connected with the renal insufficiency advancement. Negative correlation between IG, HDL-C levels (r = -0.43, p < 0.001) and TG, IIDL-C/apoAI (r = -0.56; p < 0.001) were found, which confirmed the abnormal composition of HDL molecules and indicated a high risk of atherosclerosis. CONCLUSION: Our results may indicate that of atherosclerosis in CR1 patients is connected with dyslipoproteinemia and disturbances in HDL molecular composition and with different stages of chronic renal insufficiency.

Sialic acids of young and old red blood cells in healthy subjects.

A quite simple method for obtaining young and old erythrocytes is presented. Mean corpuscular volume, glutamic oxaloacetic transaminase activity which is one of the best age parameters, and contents of total sialic acids in erythrocyte membranes were determined in whole erythrocyte population and in low (old) and high (young) density fractions separated by centrifugation of packed cells obtained from 23 healthy subjects. Glutamic oxaloacetic transaminase (GOT) activity, and contents of total sialic acids in erythrocyte membranes were significantly higher in young cells then in old ones, or in the whole population of erythrocytes. The presented results suggest that this method is simple for obtaining two different fractions of erythrocytes and that erythrocytes lose intact sialic acids together with their membrane during erythrocytes senescence.

Lipid and lipoprotein ratios as risk factors of atherosclerosis in patients with chronic renal insufficiency (CRI).

The serum levels of lipids, apolipoproteins and lipoprotein ratios in 19 healthy persons and 20 patients with uraemia not dialyzed were determined. Based on creatinine level the patients were divided into two groups: L (serum creatinine 2-5 mg/dl) and H (serum creatinine 5-10 mg/dl). Dyslipoproteinaemia in uraemic patients is already manifested in the early stages of the disease through its abnormal apolipoproteins rather than lipid profile and it suggests a high risk of atherosclerosis.

Effect of dialysis membranes on lipoprotein profile of serum in haemodialysed patients.

The subjects of the studies were 31 haemodialysed (HD) patients with chronic renal insufficiency (CRI). In this group of patients the lipoprotein profile was determined and 8 patients were selected for further studies. During the study the patients were treated with cuprophane membranes for 6 months. For the next 6 months the same patients were treated using polysulfone dialysers, and for further 6 months HD with polysulfone dialysers was continued. Patients' sera were tested after every 6 months of treatment. The delta values were calculated as 6-month HD with polysulfone minus 6-month HD with cuprophane (deltaI) and 12-month HD with polysulfone minus 6-month HD with polysulfone (deltaII). We concluded that after long-term HD with low flux polysulfone treatment the lipoprotein profiles improved, but the mechanism of the process is not clear.

Influence of intraperitoneal vancomycin on peritoneal dialysis efficiency. A clinical study.

Peritonitis is a major complication of intermittent peritoneal dialysis (IPD); over 70% of the infections are caused by Gram-positive bacteria. Vancomycin (V) is the antibiotic of choice in the treatment of peritonitis caused by G(+). The influence of vancomycin on peritoneal transport in IPD patients has not been described before. We have investigated the effect of intraperitoneal vancomycin on dialysis efficiency in 8 IPD patients using dialysis solutions containing either lactate or acetate. The following parameters were measured: net ultrafiltration (UF), concentration ratios (D/P) of urea, creatinine, potassium, peritoneal clearances (ml/min) of urea, creatinine, potassium, mass transfer of sodium (MTNa), sodium sieving index (SCNa). It has been found that vancomycin significantly decreases D/P urea (p < 0.05) and creatinine (p < 0.05). We found also a significant decrease of mean clearance of urea (p < 0.05) and creatinine (p < 0.05). The mean clearance of potassium did not change significantly. There was no significant change in UF, MTNa, and SCNa. Our preliminary data suggest that vancomycin decreases the permeability of peritoneum for certain low molecules in IPD patients which may have a negative impact on dialysis efficiency.

Plasma lipoproteins in patients with chronic renal failure (CRF).

The clinical picture in chronic renal failure (CRF) shows great variability depending on age, sex, aetiology of disease, grades of renal injury and type of treatment. Significant increases of triglycerides (TG), low-density lipoprotein cholesterol (LDL-chol) and and apo B concentrations, significant decreases of high-density lipoprotein cholesterol (HDL-chol) levels and apo A and apo AI concentrations, and no significant changes in total cholesterol (TC) have been shown in CRF patients. Significant increases of TC/HDL-chol, LDL-chol/HDL-chol, apo B/apo AI and apo B/LDL-chol ratios were also demonstrated. That indicates a high risk of atherosclerosis even when total cholesterol levels are in the normal range. There were highly significant and positive correlations between TC/HDL-chol and LDL-chol/HDL-chol ratios, apo B and LDL-chol concentrations as well as between the apo B/apo AI and LDL-chol/HDL-chol ratios.

Comparison of plasma erythropoietin concentrations and iron status in hemodialyzed patients not requiring and requiring rHuEpo therapy.

Fifty patients treated with chronic hemodialysis (HD) were observed for 1 year. 24 of them (48%) did not require treatment with recombinant human erythropoietin (rHuEpo) (group I) because the permanent hemoglobin (Hb) concentration was > 5.9 mmol/l (9.5 g/dl), hematocrit > 30%. The remaining 26 patients (group II) permanently or periodically required rHuEpo treatment. After 6 months of initial observation and after 6 months of clinical study we made a comparison of endogenous erythropoietin (Epo) and iron status in two groups of patients. Patients not requiring treatment with rHuEpo had statistically significant higher Epo concentration and lower iron reserves than patients on rHuEpo treatment. We did not find significant differences in Hb, albumin and creatinine between patients in both groups. Hb concentration did not correlate with the level of Epo, serum creatinine, transferrin saturation, ferritin, iron reserves and time of dialysis therapy in both groups. In both groups we found a significant negative correlation between the concentration of Epo and iron stores. Our results indicate that in patients on HD treatment, plasma Epo level appears to depend either directly or indirectly on iron status.

Magnesium concentration in plasma and erythrocytes in MS.

There are few reports of Mg in MS and none dealing with Mg content in erythrocytes. Mg concentration was determined in serum and in erythrocytes with the help of a BIOTROL Magnesium Calmagite colorimetric method (average sensitivity: 0.194 A per mmol/I) and a Hitachi autoanalyzer in 24 MS patients (7 men and 17 women, age 29-60; 37 years on average with the duration of the disease: 3-19; 11 years on average, at clinical disability stages according to the Kurtzke scale: 1-7; 3.2 on average, in remission stage. A statistically significant decrease (p < 0.001) of Mg concentration in erythrocytes and no changes in plasma of MS patients were found. The results obtained suggest the presence of changes in membrane of erythrocytes which could be connected with their shorter life and with affection of their function.

Influence of intraperitoneal gentamicin on peritoneal transport in IPD patients.

We have investigated the effect of intraperitoneal gentamicin on dialysis efficiency in 10 intermittent peritoneal dialysis (IPD) patients. The following parameters were measured: net ultrafiltration (UF); concentration ratios (D/P) of urea, creatinine, potassium; peritoneal clearances (ml/min) of urea, creatinine, potassium; mass transfer of sodium (MTNa); sodium sieving index (SCNa). It has been found that gentamicin significantly decreased D/P urea (p < 0.056) and D/P creatinine (p < 0.05). We found also a significant decrease of mean clearances of urea (p < 0.05) and creatinine (p < 0.05). The mean clearance of potassium did not significantly change. There was no significant change in UF, MTNa and SCNa. Our preliminary data suggest that gentamicin decreases the permeability of the peritoneum for certain low molecules in IPD patients, which may have a negative impact on dialysis efficiency.

Effect of repeated treatments with cladribine (2-chlorodeoxyadenosine) on blood counts in multiple sclerosis patients.

We report the results of blood morphology monitoring of 11 remitting-relapsing multiple sclerosis patients who received repeated treatments with cladribine (2-chlorodeoxyadenosine). The drug was given once, daily, subcutaneously (5 mg) or orally (10 mg) for 5 consecutive days, as 6 monthly courses followed by one or two additional courses at 3 or 6 month intervals. The treatments were well tolerated, although many patients suffered from incidental upper respiratory tract infections, most of which occurred during the last 6 months of the observation period. One patient had recurrent infections, including an episode of urosepsis. All infections responded to standard therapy with antibiotics. Progressive lymphocyte reduction to 1000/microliters on average, and clear, but clinically insignificant drop in thrombocytes, was observed. Granulocyte counts were sometimes markedly elevated. A few patients developed macrocytosis, but none required transfusion. With our dosing and schedule, cladribine seems relatively safe in multiple sclerosis patients.