Red blood cells and platelet membrane fatty acids in non-dialyzed and dialyzed uremics

Three groups of patients with chronic renal failure (CRF), 16 non-dialyzed, 16 undergoing haemodialysis (HD), 16 undergoing continuous ambulatory peritoneal dialysis (CAPD), and 48 controls were examined. We analyzed the fatty acid composition in membranes from erythrocytes and platelets and the platelet malondialdehyde (MDA) production as an index of thromboxane metabolism. Marked differences in erythrocytes fatty acid composition were observed between patients with CRF and controls and, particularly, among the three groups of patients with CRF. Patients on CAPD were characterized by an increase in oleic acid, while haemodialyzed had a marked increase in arachidonic acid. Platelet fatty acid composition showed similar differences, suggesting a 'systemic' membrane abnormality. Platelet MDA was increased in haemodialyzed and positively correlated with the platelet arachidonate content

Virulence factors of non-O1 non-O139 Vibrio cholerae isolated in Córdoba, Argentina Factores de virulencia de Vibrio cholerae no-O1 no-O139 aislados en Córdoba, Argentina

V. cholerae non-O1 non-O139 serogroups isolated from clinical and environmental sources in Córdoba, Argentina, were analyzed for the presence and expression of virulence genes. Most of the strains studied contained the genes toxR and hlyA, but lacked ctxA, zot, ace, tcpA and stn. The culture supernatants were tested for hemolytic and cytotoxic activity. The enterotoxic potential of the strains was studied in a rabbit ileal loop assay and their genetic profiles were compared by PFGE. The environmental strains varied in their virulence phenotype and showed no-clonal relationships. The clinical strains were highly enterotoxic, hemolytic, proteolytic and showed indistinguishable PFGE profiles, although they differed in their cytotoxic activity. This is the first description, using cell culture and &#8220;in vivo&#8221; studies, of the virulence properties of non-O1 non-O139 V. cholerae from Argentina.<br>En este trabajo se analizó la presencia y expresión de genes de virulencia en V. cholerae no-O1 no-O139 de origen clínico y ambiental, aislados en Córdoba, Argentina. La mayoría de las cepas estudiadas contiene los genes toxR y hlyA, pero no ctxA, zot, ace, tcpA y stn. Se analizó la actividad hemolítica y citotóxica de estas cepas en los sobrenadantes de cultivo, así como su potencial enterotóxico en ensayos de asa ileal ligada de conejo. Además, los aislamientos fueron comparados por sus perfiles genéticos en PFGE. Las cepas del medio ambiente mostraron variación en su fenotipo de virulencia y no mostraron relación clonal. Las cepas clínicas fueron muy enterotóxicas, hemolíticas, proteolíticas y mostraron perfiles indistinguibles de PFGE, aunque mostraron diferencias en su actividad citotóxica. En este trabajo se describen por primera vez, utilizando ensayos de cultivo celular e &#8220;in vivo&#8221;, propiedades de virulencia de V. cholerae no-O1 no-O139 aislados en Argentina

Surface decoration with gH625-membranotropic peptides as a method to escape the endo-lysosomal compartment and reduce nanoparticle toxicity

The membranotropic peptide gH625 is able to transport different cargos (i.e., liposomes, quantum dots, polymeric nanoparticles) within and across cells in a very efficient manner. However, a clear understanding of the detailed uptake mechanism remains elusive. In this work, we investigate the journey of gH625-functionalized polystyrene nanoparticles in mouse-brain endothelial cells from their interaction with the cell membrane to their intracellular final destination. The aim is to elucidate how gH625 affects the behavior of the nanoparticles and their cytotoxic effect. The results indicate that the mechanism of translocation of gH625 dictates the fate of the nanoparticles, with a relevant impact on the nanotoxicological profile of positively charged nanoparticles

Hypertension in primary immunoglobulin A nephropathy (Berger's disease): hemodynamic alterations and mechanisms

Twenty-two patients with primary IgA nephropathy (Berger's disease), 12 with normal and 10 with high blood pressure, were studied. The mean intra-arterial pressure was 88 +/- 6 mm Hg in the normotensive group and 113 +/- 10mm Hg in hypertensive patients; plasma renin activity was high in normotensives and normal in hypertensives. The glomerular filtration rate was 83 +/- 23 and 73 +/- 26 ml/m in 1.73 m2 in normotensive and hypertensive patients, respectively (p = n.s.). Blood volume was high in IgA nephropathy patients: 82 +/- 12 ml/kg body weight in normotensives and 96 +/- 7 ml/kg body weight in hypertensives. Mean arterial pressure was significantly correlated with blood volume (r = 0.541, p less than 0.01), but not with plasma renin activity and glomerular filtration rate. The cardiac index was high in both groups: 4.20 +/- 0.88 liters/min/m2 in normotensive and 3.95 +/- 0.87 liters/min/m2 in hypertensive patients. The total peripheral resistance index was significantly lower than normal in normotensives (1,659 +/- 387 dyn/s/cm-5/m2) and significantly higher (2,419 +/- 562 dyn/s/cm-5 m2) in hypertensives. The cardiac index did not correlate with blood volume and mean arterial pressure; a positive correlation was found between mean arterial pressure and peripheral vascular resistance (r = 0.630, p less than 0.01). No correlation was observed between blood volume and plasma renin activity. Our study indicates that hypertension in IgA nephropathy is primarily volume dependent, and that this increase in blood volume is not related to the deterioration of renal function. The role of the renin-angiotensin system in the maintenance of the hypertension is not well-defined.(ABSTRACT TRUNCATED AT 250 WORDS

Increased susceptibility of LDL to in vitro oxidation in patients on maintenance hemodialysis: effects of fish oil and vitamin E administration.

Oxidized low-density lipoproteins (LDL) play an important role in the pathogenesis of atherosclerosis. An increased sensitivity of red blood cell membranes to lipid peroxidation has been previously demonstrated in patients with chronic renal failure, suggesting that the antioxidant defence of lipoproteins might be impaired. Fish oil supplementation has been proposed in dialysis patients, but it is still unclear if the positive effects of fish oil depend only on its polyunsaturated fatty acid content or on other factors, such as the usually added antioxidants. Moreover, the increased concentration of highly peroxidable n-3 polyunsaturated fatty acids induced by fish oil in LDL particles could favour LDL oxidation and possibly the development of atherosclerosis. The present study was designed to evaluate the susceptibility of LDL to in vitro oxidation (lag phase) and the rate of lipid peroxidation (propagation phase) by fluorescence development during copper exposure in 14 hemodialysis patients. A further aim was to compare the effects on lipid metabolism and LDL oxidation of fish oil supplementation (20 ml containing vitamin E 20 IU as antioxidant) for 30 days and of vitamin E administration (50 IU) for another 30 days. The length of the lag phase and vitamin E concentration were significantly reduced (p lt 0.01) in hemodialysis patients and increased significantly (p lt 0.01) after administration of both fish oil and vitamin E. Fish oil supplementation also reduced plasma lipids significantly (p lt 0.01) and increased the propagation phase (p lt 0.01). Our results demonstrate that the susceptibility of LDL to oxidation is enhanced in hemodialysis patients, suggesting a possible relationship between excessive LDL peroxidation and accelerated atherosclerosis. The increased susceptibility of LDL to in vitro oxidation can be explained, at least partially, by a reduced LDL vitamin E concentration. Since fish oil increased the lag phase to the same extent as vitamin E supplementation, the positive effect of fish oil could be partly explained by its antioxidant content

A controlled randomized european multicenter study (CREMS) on mortality in chronic dialysis (CD) patients: a comparison between acetate-free biofiltration (AFB) and conventional bycarbonate dialysis (BD)

Introduction and Aims: The exact role of the absence of acetate in dialysate has not yet been clarified in randomized studies. Previous trials focused on intradialytic symptoms, where as few studies have attempted to obtain a better survival and a lower morbidity with AFB. To evaluate whether AFB may alter long-term mortality compared to BD, we conducted a CREMS in 362 incidents, critically ill CD pts, defined as elderly (&gt;60 y old) orhypotension prone ( 655 hypotensive episodes/month) or diabetics, from 94 European Dialysis Centres during the period 1998 \u2013 2003.Methods: Pts (211 male, 151 female, aged 68\ub19 y) were allocated to BD (192 pts) or to AFB (170 pts) by block randomization. The role of BD or AFB treatment, adjusted for baseline demographics, co-morbidities (as measured by the Charlson Co-morbidity Index, CCI), BMI, predialysis systolic blood pressure (pSBP) (stratifying pts in: normotensives, N, if pSBP &lt;140 mmHg, mildly hypertensives, MH, if pSBP 140 -160 mmHg, severe hypertensives, SH, if pSBP &gt;160 mmHg), left ventricular mass (LVM), lipids, spKt/V, hemoglobin, albumin, Ca-P product as predictors of 4-y all-cause (ACM) and cardiovascular (CVM) mortality, was evaluated by Cox\u2019s analysis.Results: The two groups were homogeneous for baseline characteristics, except for the higher prevalence of hypotension-prone pts in AFB (39.4% vs 26.6% in BD; p=0.010). Drop out were 20% in BD and 24% in AFB.ACM was 30% in BD and 33% in AFB with an average annual mortality rate of 11.3%. Deaths for CV disease were 22% in BD and 15% in AFB (p=0.010). Vascular access (HR 1.88; 95%CI 1.02-3.46 CVC/PTFE vs AVF; p=0.043), higher baseline CCI (HR 1.22; 95%CI 1.07-1.39; p=0.002) and left ventricular hypertrophy (LVH) (HR 1.68; 95%CI 1.05-2.71; p=0.032)were significant predictors of ACM. CCI (HR 1.26; 95%CI 1.08-3.46; p=0.004) and Ca-P product (HR 1.02; 95%CI 1.00-1.03; p=0.039) were the only predictors of CVM.Treatment modality, indeed, as well as CCI, and change in pSBP during the follow-up were significant determinants in the large subset of mild hypertensive pts (Table)

CARDIOVASCULAR EFFECTS OF ACETATE-FREE BIOFILTRATION (AFB) AND CONVENTIONAL BICARBONATE DIALYSIS (BD) IN CHRONIC DIALYSIS (CD) PATIENTS: A CONTROLLED RANDOMIZED EUROPEAN MULTICENTER STUDY

Introduction and Aims: Acetate-free Biofiltration (AFB) has been shown to improve intradialytic hemodynamic stability in previous short-term studies, whereas very little is known on its long-term cardiovascular effects. We performed a 3-y prospective randomized European multicenter study to evaluate the cardiovascular effects of long-term AFB in incident CD patients (pts), compared to conventional bicarbonate dialysis (BD). Methods: Threehundred-sixtytwo pts (211 male, 151 female, aged 68\ub19 y) were enrolled and allocated to BD (n 192) or to AFB (n 170) by block randomization. Pts were stratified according to predialysis systolic blood pressure (pSBP) in normotensives (N) (pSBP <140 mmHg) (n 138: 69 on BD and 69 on AFB), mildly hypertensives (MH) (pSBP 140-160 mmHg) (n 146: 85 on BD and 61 on AFB) and severe hypertensives (SH)(pSBP >160 mmHg) (n 78: 38 on BD and 40 on AFB). Outcomes of the study were changes in pSBP, left ventricular mass (LVM) and intradialytic cardiovascular instability (defined as the appearance of intradialytic hypoand/or hypertensive episodes). The effects on cardiovascular mortality (CVM) were evaluated over 4-y follow-up. Results: During follow up, median pSBP did not change in BD (from 146 to 144 mmHg, p=0.127) and significantly decreased in AFB (from 145 to 138 mmHg, p=0.004). The pSBP changes in AFB were only significantly different from BD in MH (-5 vs -2 mmHg, p=0.050). The proportion of subjects with intradialytic cardiovascular instability was unchanged in BD (from 56 to 46%, p=0.196) and significantly decreased in AFB (from 69% to 44%, p=0.003). In the three subgroups, we observed the same pattern in favour of AFB. Median LVM tended to decrease in AFB (from 142 to 140 g/m2, p=0.597) while it increased in BD (from 137 to 142 g/m2, p=0.138) even though did not achieve the statistical significance. On the contrary, LVM in MH pts significantly increased in BD (from 133 to 148 g/m2, p=0.002) and did not change in AFB (from 157 to 155 g/m2, p=0.940). The proportion of pts who died for CV disease was higher in BD than AFB, in MH (27% vs 8%, p=0.005). In the same subgroup, significant determinants of CVM were CCI (HR 1.27, 95%CI 1.05 -1.55, p=0.015), treatment modality (AFB: HR 0.31, 95%CI 0.12-0.8, p=0.017) and the change in pSBP (HR 1.04, 95%CI 1.00-1.09, p=0.044). Conclusions: Our study shows that long-term AFB is associated with a better intra- and inter-dialytic blood pressure control than BD. Results also suggest that AFB reduces CVM in the mildly hypertensive patients, possibly via the reduction of pSBP, the better intradialytic cardiovascular stability, and the prevention of the increase in LV