Effect of dialysis on erythrocyte membrane of chronically hemodialyzed patients

The present work examines the role of uremia and the effect of dialysis treatment on red blood cells (RBCs) membrane properties of hemodialysis patients. The results showed that, the uremic patients had a lower values of erythrocyte deformability than that of healthy control subject. The median osmotic fragility (MOF) showed a significant increase in hemodialyzed patients than that for control group. The osmotic resistance to hemolysis was improved after dialysis. The solubilization process of the RBCs membrane showed that the detergent concentration needed to solubilize the RBCs membrane for uremic patient was much higher than that for control group. The abnormalities of the present results for RBCs membrane properties are mostly related to membrane fluidity, which are slightly improved after dialysis. Biochemical analysis showed a decreasing trend in RBCs count, urea nitrogen, creatinine, potassium,     

Plasma fatty acid composition in continuous ambulatory peritoneal dialysis patients: an increased omega-6/omega-3 ratio and deficiency of essential fatty acids

Patients with end-stage renal disease, including those treated with peritoneal dialysis, have a high risk for death, particularly from cardiovascular causes. Plasma fatty acid (FA) composition is used as an indicator of disease risk, because its alteration has been related to metabolic disease and cardiovascular disease. For this purpose, we have measured plasma FA composition in continuous ambulatory peritoneal dialysis (CAPD) patients and compared them with those of healthy subjects. This study was performed on 51 (21 M, 30 F) CAPD patients at least 6 months under dialysis, aged 20-75 years (mean 47.81 ± 11.8 years) and 45 (25 M, 20 F) healthy control subjects aged 20-60 years (mean 38.62 ± 12.9 years). Plasma 10-cis-pentadecanoic acid, 10-cis-heptadecanoic acid, heneicosanoic acid, tricosanoic acid, nervonic acid, saturated fatty acid, and monounsaturated FA levels and delta 9 desaturase activity were significantly higher whereas linoleic acid, linolenic acid, 11,14-eicosedienoic acid, arachidonic acid, docosahexaenoic acid, and omega-3 FA levels were significantly lower in the CAPD group than those in the healthy group. Our results show that there are FA abnormalities and especially a depletion in essential FA levels and a high level of omega-6/omega-3 ratio in CAPD patients, the underlying mechanism of which is not known and needs to be investigated. Therefore, we believe that essential FA supplementation should be encouraged for CAPD patients.     

Changes in fatty acids composition in cerebrospinal fluid of patients with myelopathy

The composition of fatty acids in the cerebrospinal fluid of patients with cervical myelopathy, thoracic myelopathy, cauda equina syndrome, and spinal cord injury were measured by gas chromatography. The relationship between the change in fatty acids composition and the improvement of symptoms and pathology were studied. The percent distribution of eicosadienoic acid (C20: 2) in fatty acids composition was found to be significantly increased in the cerebrospinal fluid of patients with cervical and thoracic myelopathies (p less than 0.05), and with incomplete spinal cord injury (p less than 0.01) against control group. Although the high percent distribution, especially over 10%, of C20: 2 in the cerebrospinal fluid of the patients with cervical or thoracic myelopathy before operation decreased after operation, no correlation was found between the decrease of percent distribution of C20: 2 and improvement of symptoms. A positive relationship was found between the decrease of percent distribution of C20: 2 and the improvement in symptom of patients with central spinal cord injury.     

Malignant hyperthermia: an altered phospholipid and fatty acid composition in muscle membranes

There is thought to be a genetic defect within the calcium release channel of the sarcoplasmic reticulum in malignant hyperthermia (MH). This primary alteration is hypothesized to influence the function and/or structure of various muscle membrane systems; e.g., to have a direct effect on the composition of the lipid matrix. Therefore, in striated muscle samples, we determined the quantity and fatty acid composition of the various types of membrane phospholipids. German Landrace pigs were classified as normal or susceptible to MH. Total lipid content from longissimus dorsi, semi-membranosus muscle, and heart left ventricular (HLV) samples were extracted with chloroform/methanol and subsequently separated by high performance liquid chromatography. The single phospholipid fractions were collected and, following derivatization, the quantities of individual fatty acids were determined using a capillary gas chromatographic method. In general, samples from the susceptible pigs contained lower absolute amounts of individual phospholipids. The most notable differences occurred in the HLV, where phosphatidylinositol, phosphatidylserine, phosphatidylethanolamine and sphingomyelin were all significantly less (P less than or equal to 0.05). The muscle from the susceptible animals also contained decreased amounts of the polyunsaturated phospholipid-bound fatty acids (P less than or equal to 0.05). These differences in phospholipid and fatty acid concentrations of membranes isolated from swine susceptible to MH may relate to their apparently increased sensitivities to halothane (e.g., fluidizing effects) or elevated temperature.     

Relationship between plasma phospholipid polyunsaturated fatty acid composition and bone disease in renal transplantation

To investigate the relationship between polyunsaturated fatty acid (PUFA) and bone metabolism in renal transplant patients, plasma phospholipid (PP) PUFA levels, biochemical markers of bone turnover and bone mineral density (BMD) were determined in 22 recipients of a first renal allograft at baseline and after a mean 24.4 month follow-up. A significant increase in PP n-3 PUFA content, in the [n-3 PUFA/ arachidonic acid] ratio and in BMD values was observed, as well as a close correlation between the increase in PP n-3 PUFA content and femoral neck BMD. Multivariate regression analysis showed that BMD improvement was positively related to PP n-3 PUFA variation and baseline PP eicosapentaenoic acid levels, and negatively to PP arachidonic acid modification. Tacrolimus- versus cyclosporine-treated patients demonstrated a significant increase in femoral neck BMD and PP n-3 PUFA content. This is the first longitudinal study showing a link between PP-PUFA composition and bone disease in renal transplantation.     

Bacterial meningitis in hemodialyzed patients

BACKGROUND: To analyze the clinical features, causative pathogens and therapeutic outcomes of bacterial meningitis in hemodialyzed patients. PATIENTS AND METHODS: Two hundred and sixty-seven patients, > or = 16 yrs, were identified with culture-proven bacterial meningitis. In addition, the causative pathogens and therapeutic outcomes between uremic and non-uremic patients with adult bacterial meningitis were analyzed. RESULTS: Nine uremic patients with bacterial meningitis, accounting for 3% (9/267) of our adult patients with culture-proven bacterial meningitis had fever, disturbed consciousness and seizures. These were the three most common manifestations in our patients. The interval between the onset of symptoms and therapy start was 5-11 days (mean: 9 days). No patients were initially diagnosed with bacterial meningitis, two patients were initially suspected of having infection of unknown origin. In the non-uremic patient group, klebsiella pneumoniae, Staphylococcus aureus, and Streptococcus pneumoniae were the most frequently detected pathogens, while pseudomonas aeruginosa and coagulase-negative Staphylococcus were the most prevalent in the uremic patients group. The overall mortality rates for the non-uremic and uremic patient groups were 33 and 78% respectively. CONCLUSION: The mortality rate for bacterial meningitis in the uremic patients group remained high. Due to non-specific manifestations and slow evolution, bacterial meningitis was commonly misdiagnosed as uremic encephalopathy. Therefore, effective treatment was usually delayed. To avoid treatment failure, early diagnosis, careful monitoring of clinical condition and appropriate antibiotic choices are necessary.     

Relationship of erythrocyte membrane polyunsaturated fatty acids and prostate-specific antigen levels in Jamaican men

OBJECTIVE: To investigate the relationship between erythrocyte membrane polyunsaturated fatty acid (PUFA) and serum prostate- specific antigen (PSA) levels in Jamaican men, as there may be an association between prostate cancer incidence and dietary fatty acids, and prostate cancer incidence in Jamaica is among the highest in the world. PATIENTS AND METHODS: Blood from 107 Jamaican men was analysed for 32 individual fatty acids and PSA levels. Special attention was given to correlations between Omega3 and Omega6 PUFAs and PSA. Data were analysed using standard linear regression methods. RESULTS: The mean PSA was 18.6 ng/mL (normal 0-4.0); for age groups of 51-60, 61-70 and 71-80 years the levels were 14, 26 and 23 ng/mL, respectively. Eicosapentaenoic acid (Omega3) levels decreased as PSA exceeded 10 ng/mL (P = 0.02). Arachidonic acid (Omega6) levels decreased as PSA was < 2 ng/mL (P = 0.02). Linoleic acid (Omega6) levels decreased in men with PSA levels of 2-10 ng/mL (P = 0.04). In men with a PSA of > 10 ng/mL there was a positive correlation between the ratio of Omega6 to Omega3 PUFAs and PSA (P = 0.036); there was also a negative correlation between the ratio of Omega3 to Omega6 PUFAs and PSA (P = 0.08). When the ratio of Omega3 PUFAs over the products of Omega6 PUFAs were used, this trend was significant (P= 0.03). CONCLUSIONS: Increased levels of Omega6 PUFAs and the ratio of Omega6/Omega3 PUFAs in Jamaican men are associated with an increased mean PSA level and risk of prostate cancer. Additional studies are needed to establish a causal link between dietary fatty acid intake and the development of prostate cancer in Jamaican men.     

Plasma fatty acids and the control of lipolysis by cathecholamines.

The role of lipolysis in adipose tissue is described in relation to the maintentance of plasma levels of fatty acids. The molecular details of the hormonal control of lipolysis in the human adipocyte are discussed.     

Influence of dietary fat composition on development of insulin resistance in rats. Relationship to muscle triglyceride and omega-3 fatty acids in muscle phospholipid

High levels of some but not all dietary fats lead to insulin resistance in rats. The aim of this study was to investigate the important determinants underlying this observation. Insulin action was assessed with the euglycemic clamp. Diets high in saturated, monounsaturated (omega-9), or polyunsaturated (omega-6) fatty acids led to severe insulin resistance; glucose infusion rates [GIR] to maintain euglycemia at approximately 1000 pM insulin were 6.2 +/- 0.9, 8.9 +/- 0.9, and 9.7 +/- 0.4 mg.kg-1. min-1, respectively, versus 16.1 +/- 1.0 mg.kg-1.min-1 in chow-fed controls. Substituting 11% of fatty acids in the polyunsaturated fat diet with long-chain omega-3 fatty acids from fish oils normalized insulin action (GIR 15.0 +/- 1.3 mg.kg-1.min-1). Similar replacement with short-chain omega-3 (alpha-linolenic acid, 18:3 omega 3) was ineffective in the polyunsaturated diet (GIR 9.9 +/- 0.5 mg.kg-1.min-1) but completely prevented the insulin resistance induced by a saturated-fat diet (GIR 16.0 +/- 1.5 mg.kg-1.min-1) and did so in both the liver and peripheral tissues. Insulin sensitivity in skeletal muscle was inversely correlated with mean muscle triglyceride accumulation (r = 0.95 and 0.86 for soleus and red quadriceps, respectively; both P less than 0.01). Furthermore, percentage of long-chain omega-3 fatty acid in phospholipid measured in red quadriceps correlated highly with insulin action in that muscle (r = 0.97). We conclude that 1) the particular fatty acids and the lipid environment in which they are presented in high-fat diets determine insulin sensitivity in rats; 2) impaired insulin action in skeletal muscle relates to triglyceride accumulation, suggesting intracellular glucose-fatty acid cycle involvement; and 3) long-chain omega-3 fatty acids in phospholipid of skeletal muscle may be important for efficient insulin action.     

Osmolal gap in hemodialyzed uremic patients

Osmolality is an expression of the number of particles in a given weight of solvent (mOsm). Measured osmolality is determined by the osmometer, and calculated osmolality is estimated by 2xNa + UN/2.8 + glucose/18. The difference between measured and calculated osmolality is the osmolal gap. The purpose of the present study is to determine the measured and the calculated osmolality and the osmolal gap in hemodialyzed uremic patients, pre- and post-hemodialysis (HD). In 24 uremic patients under regular HD, blood samples pre- and post-HD were collected, and serum osmolality measured (osmometer) and calculated (2xNa + UN/2.8 + glucose/18) and the osmolal gap (measured-calculated osmolality) were determined. Also, the same parameters were determined in 22 healthy subjects (control). According to our findings, the measured osmolality in patients is significantly higher pre- and post-HD in comparison to that of controls, but post-HD is significantly lower than pre-HD. Also, calculated osmolality is significantly higher pre- and post-HD in comparison to that of controls, but the value post-HD is significantly lower than the pre-HD. The osmolal gap of patients pre-HD (11 ± 2.08) and post-HD (7.29 ± 1.94) is significantly higher (P < 0.001) in comparison to that of controls (3.18 ± 1.46); also, the value post-HD is significantly decreased in comparison to the value pre-HD (P < 0.001). Uremic hemodialyzed patients present high measured and calculated osmolality pre-HD that remains high post-HD in comparison to that of controls in spite of the significant decrease post-HD in comparison to that of pre-HD. Also, the osmolal gap is high pre-HD and, in spite of the decrease, remains high post-HD. In comparison to that of controls, the high osmolal gap indirectly indicates the presence of unidentified endogenous osmoles in the serum of uremic patients which partly are removed during HD.     

Decreased erythrocyte (Ca2+ + Mg2+)-ATPase activity in hemodialyzed uremic patients.

Erythrocyte (Ca2+ + Mg2+)-ATPase activity and calcium content were determined in 15 uremic-hemodialyzed patients and 15 normal controls. A decrease in the activity of the enzyme (mean +/- SD = 65 +/- 7 vs. 79 +/- 12 mumol Pi/g Hb/h, p less than 0.001) and a parallel increase in the calcium content (17.2 +/- 6.4 vs. 5.1 +/- 4.2 mumol/L RBC, p less than 0.05) were found in the patients' erythrocytes when compared with those of the controls. It is proposed that malfunction of the calcium pump in hemodialyzed uremic patients is pathophysiologically significant in the accumulation of intracellular calcium. The increased intracellular calcium found in other tissues in uremia may be the result of the systemic malfunction of (Ca2+ + Mg2+)-ATPase in this disorder.     

Relationship between body composition,sex hormones and leptinemia in hemodialyzed patients with chronic renal failure

BACKGROUND: Females are characterized by significantly higher plasma leptin concentration than males. It seems likely that sex hormones influence leptinemia independently from differences in body composition. The aim of the present study was to analyze the contribution of plasma concentrations of testosterone and estradiol on leptinemia in hemodialyzed patients. METHODS: 110 hemodialyzed patients--HD (60 M, 50 F) and 70 healthy subjects (HS) (30 M, 40 F) were enrolled in this study. Plasma leptin, testosterone or estradiol and CRP concentrations and body composition by dual-energy X-ray absorptiometry (DEXA) were assessed. RESULTS: Total body fat was significantly higher in females than in males (27.5 +/- 1.5% vs. 17.2 +/- 1.0% of body weight in HD and 36.0 +/- 1.0% vs. 18.2 +/- 1.4% in HS, respectively). Plasma leptin concentrations were markedly higher in females than in males both in HD (27.9 +/- 5.4 ng/ml vs. 9.6 +/- 1.9 ng/ml) and HS (16.5 +/- 1.7 ng/ml vs.3.1 +/- 0.4 ng/ml). A highly significant, strong positive correlation was found between total fat mass (TFM) and leptinemia in all studied groups. No significant univaried correlation between plasma leptin and testosterone or estradiol concentrations respectively was found both in HD and HS. Multiple regression analyses showed that the main determinant of leptinemia is TFM (beta = 0.623 and 0.798 in HS females and males respectively, and beta = 1.058 and 0.797 in HD females and males respectively). Plasma concentration of testosterone (beta = -0.139 and beta = -0.075 in male HD and HS respectively) and estradiol (beta = 0.199 and beta = 0.046 in females HD and HS, respectively) contributed to leptinemia only in a minor degree. CONCLUSION: Both testosterone and estradiol are minor contributors to leptinemia both in HS and HD patients. The main determinant of leptinemia in these subjects is total body fat mass.     

Modulation of Kupffer cell membrane phospholipid function by n-3 polyunsaturated fatty acids

Dietary n-3 polyunsaturated fatty acids (PUFAs) have been reported to improve clinical outcome in a number of inflammatory diseases including burns and sepsis. One mechanism contributing to the anti-inflammatory effect is the incorporation of n-3 PUFAs into membrane phospholipids which decreases macrophage eicosanoid production. We hypothesize that an additional mechanism for their effects is an alteration of membrane signal transduction that decreases macrophage responsiveness to inflammatory stimuli. Kupffer cells, the fixed macrophages of the liver, were obtained from rats pair fed diets for 6 weeks with 15% of calories supplied as menhaden (high n-3), corn (control), or safflower (high n-6) oils. The effects of the dietary oils on Kupffer cell membrane signal transduction and eicosanoid production were assessed by measuring inositol phospholipid (PI) metabolism, intracellular calcium responses, and prostaglandin E2 (PGE2) production to the inflammatory signals endotoxin (LPS) and platelet activating factor (PAF). The menhaden oil diet resulted in significant incorporation of n-3 PUFAs into total cellular PUFAs compared to corn and safflower oil. (total n-3 PUFAs, 28.1% menhaden vs 2.1% corn vs 1.2% safflower, P less than 0.03). This incorporation altered signal transduction of PAF as both PI turnover (65% +/- 10% of corn oil) and calcium response (0.6-fold vs 5.0-fold for corn oil) were significantly reduced in the menhaden oil group. (P less than 0.05) The menhaden oil diet also reduced significantly PGE2 production in response to PAF and LPS (corn, 348 +/- 23 pg/ml; menhaden, 48 +/- 6 pg/ml, P less than 0.01). We conclude that, in addition to modulating eicosanoid production, n-3 PUFAs can also alter macrophage membrane signal transduction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Arterial hypotension in chronic hemodialyzed patients

We studied in 32 patients on maintenance hemodialysis (duration of treatment 6 to 133 months) whether duration of dialysis treatment affects blood pressure, plasma noradrenaline levels and alpha 2-adrenoceptor density (assessed in platelet membranes by 3H-yohimbine binding). Plasma noradrenaline levels were a significant inverse correlation to platelet alpha 2-adrenoceptor density. In addition, mean arterial blood-pressure, plasma noradrenaline levels and platelet alpha 2-adrenoceptor density were significantly related to the duration of treatment: with increasing duration of treatment plasma noradrenaline levels increased, whereas mean arterial blood-pressure and platelet alpha 2-adrenoceptor density decreased. Furthermore, changes in mean arterial blood-pressure were inversely related to plasma noradrenaline levels and positively to platelet alpha 2-adrenoceptor density. Platelet alpha 2-adrenoceptor changes were accompanied by similar alterations in (vascular) alpha 1-adrenoceptor responsiveness (assessed by blood pressure responses to i.v. injections of phenylephrine); in hypotensive hemodialysis patients, who had high, plasma noradrenaline levels and low, platelet alpha 2-adrenoceptor density, the dose of phenylephrine necessary to increase systolic blood pressure by 20 mm Hg was nearly twice as high as in normotensive dialysis patients and healthy controls. In autonomic tests, Valsalva-ratio was lower in hypotensive than in normotensive dialysis patients and healthy controls, whereas no differences were found in blood pressure and heart rate responses during sustained hand-grip exercise as well as in beat-to-beat variation during deep breathing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of hemodialysis on the content of fatty acids in monolayers of erythrocyte membranes in patients with chronic renal failure

Lipid metabolism disorders are found in patients with chronic renal failure (CRF). Changes in the content of fatty acids of the phospholipid fraction of erythrocyte membranes can lead to changes in the rheological properties. The objective of our study was to assess the effect of hemodialysis on the composition of fatty acids in two fractions of phospholipids: sphingomyelin (SPH, representative of the external monolayer) and phosphatidylethanolamine (PE, representative of the internal monolayer). Venous blood was drawn from patient with CRF before and after the HD procedure. Lipids from the erythrocyte stroma were extracted using the Rose and Oklander method and then were separated into phospholipid fractions using thin-layer chromatography (TLC). PE and SPH fractions were extracted, and the fatty acid profile was determined using gas chromatography (Perkin Elmer 8400; RTx 2330 column; length: 105 m). In the phospholipid fractions tested, a high content of saturated FA with a medium carbon chain (C 16:0 to C 18:2) and a long carbon chain such as C 24:0, C 24:1; C 22:6; and C 26:0 was found. The HD procedure affected the FA profile in the fractions tested. The proportion of saturated and unsaturated long-chain FA (above 18 C) increased in PE. However, the content of medium-chain FA C 16:0 to C 18:1 decreased. A significant decrease in the content of the majority of long-chain FA could be noted in SPH. The ratio of unsaturated (U) to saturated (S) fatty acids in the SPH fraction increased. Hemodialysis has a significant effect on the content of fatty acids in the PE and SPH fractions of erythrocyte membranes in patients with CRF.