An integrative approach to the anatomy of Syllis gracilis Grube, 1840 (Annelida) using micro-computed X-ray tomography.

BACKGROUND: The overall anatomy of the genus Syllis (Annelida: Syllidae) has been largely studied; however, an integrative approach considering different anatomical techniques has never been considered. Here, we use micro-computed X-ray tomography (micro-CT) to examine the internal anatomy of Syllis gracilis Grube, 1840, along with other widely available techniques. METHODS: We studied the anatomy of the marine annelid S. gracilis through an integrative approach, including micro-CT along with stereo and light compound microscopy (STM, LCM), scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM) and histological sectioning (HIS). In this manner, we evaluated the applicability of micro-CT for the examination of annelid anatomy by testing whether the images obtained make it possible to visualize the main body structures, in comparison with other current techniques, of the various elements of its internal anatomy. RESULTS: Overall external and internal body elements are clearly shown by the integrative use of all techniques, thus overcoming the limitations of each when studied separately.Any given method shows disparate results, depending on the body part considered. For instance, micro-CT provided good images of the external anatomy, including relevant characters such as the shape, length and number of articles of dorsal parapodial cirri. However, it is especially useful for the examination of internal anatomy, thus allowing for 3D visualization of the natural spatial arrangement of the different organs. The features best visualized are those of higher tissue density (i.e., body musculature, anterior parts of the digestive tract), particularly in 3D images of unstained specimens, whereas less electrodense tissues (i.e., the peritoneal lining of septa and nervous system) are less clearly visualized. The use of iodine stain with micro-CT has shown advantages against non-staining for the adequate observation of delicate elements of low density, such as the segmental organs, the connective between the ganglia, the ventral nerve cord and segmental nerves. DISCUSSION: Main external anatomical elements of S. gracilis are well shown with micro-CT, but images show lesser optical resolution and contrast when compared to micrographs provided by SEM and CLSM, especially for fine structural features of chaetae. Comparison of micro-CT and HIS images revealed the utility and reliability of the former to show the presence, shape and spatial disposition of most internal body organs; the resolution of micro-CT images at a cellular level is, however, much lower than that of HIS, which makes both techniques complementary.

Pegylated interferon (alone or with ribavirin) for chronic hepatitis C in haemodialysis population.

BACKGROUND/AIMS: Hepatitis C virus infection remains prevalent among patients undergoing long-term haemodialysis and has a detrimental impact on survival in this population. Antiviral therapy for chronic hepatitis C in haemodialysis patients is still a challenge to clinicians. The aim of the current study is to evaluate the efficacy and safety of therapy with pegylated interferon, alone or combined with ribavirin, for chronic hepatitis C among patients undergoing long-term hemodialysis. METHODS: We conducted a retrospective, multicenter cohort trial with monotherapy (pegylated interferon) (n=21) or combined antiviral therapy (pegylated interferon plus ribavirin) (n=5) for chronic hepatitis C in patients undergoing long-term haemodialysis. RESULTS: Sustained virological response was obtained in eleven (42%) patients. Seven (26.9%) patients interrupted prematurely the antiviral treatment due to serious side-effects, the most frequent cause of treatment withdrawal being hematological (n=3). HCV RNA load was lower in responder than non-responder patients, 5.44 (3.45; 6.36) vs. 5.86 (4.61; 6.46) log10 copies/mL, even if the difference was not significant (P=0.099). Blood transfusion requirement was greater in patients on combined antiviral therapy than those on pegylated interferon alone, 100% (5/5) vs. 0% (0/21), P=0.0001. No difference in sustained viral response occurred between patients on combined antiviral therapy and those on pegylated interferon monotherapy [40% (2/5) vs. 42.8% (9/21), P=0.90]. CONCLUSIONS: Results from this study showed that pegylated interferon alone or with ribavirin is unsatisfactory in terms of efficacy and safety. Prospective trials based on interferon-free regimens (i.e., sofosbuvir plus ribavirin or sofosbuvir plus daclatasvir) are under way in patients with hepatitis C receiving long-term hemodialysis.

External sense receptors in microdrile oligochaetes (Annelida, Clitellata) as revealed by scanning electron microscopy: Typology and patterns of distribution in the main taxonomic groups.

This work summarizes the observations on 30 species of microdriles belonging to the families Naididae (Rhyacodrilinae, Pristininae, Naidinae, Phallodrilinae, and Tubificinae), Phreodrilidae, Lumbriculidae, and Enchytraeidae using scanning electron microscopy. The lumbricid Eiseniella tetraedra, a megadrile species common in typical microdrile habitats, was used for comparison. Microdriles display external ciliate sense structures along the entire body; even at the clitellum and in budding and regeneration zones. According to the shape of the cilia, these sense structures can be divided into receptors of blunt cilia, receptors of sharp cilia, and composed receptors. Sense receptors can be morphologically unconspicuous or clearly defined on sensory buds or papillae. All microdriles studied have receptors of blunt cilia. Enchytraeids have characteristic receptors of short cilia. Pristina (Pristininae), Chaetogaster, Ophidonais, and Stylaria (Naidinae) have receptors of long blunt cilia. Composed receptors were found only in some microdriles and E. tetraedra. Receptors of sharp cilia have been found in most microdriles. Enchytraeids might be the only exception, but sharp cilia are probably present in the amphibiotic Cognettia sphagnetorum. Sensory cells with long sharp cilia might play a rheoreceptor role, and their presence in E. tetraedra and C. sphagnetorum would imply the reappearing of an ancient character that was probably lost with the transit from aquatic to terrestrial habitats. Some lumbriculids have ciliated fields. Anatomically, these structures appear as intermediate between the typical isolate sensory structures of microdriles and the sensillae of the hirudineans. The general pattern in microdriles is that uniciliate receptors and multiciliate receptors are separated, which supports the presumed aquatic origin of the clitellates.

A novel methodology for the analysis of membrane and cytosolic sub-proteomes of erythrocytes by 2-DE.

With the aim of studying a wide cohort of erythrocyte samples in a clinical setting, we propose here a novel approach that allows the analysis of both human cytosolic and membrane sub-proteomes. Despite their simple structure, the high content of hemoglobin present in the red blood cells (RBCs) makes their proteome analysis enormously difficult. We investigate here different strategies for isolation of the membrane and cytosolic fractions from erythrocytes and their influence on proteome profiling by 2-DE, paying particular attention to hemoglobin removal. A simple, quick and satisfactory approach for hemoglobin depletion based on HemogloBind reagent was satisfactorily applied to erythrocyte cells, allowing the analysis of the cytosolic sub-proteome by 2-DE without major interference. For membrane proteome, a novel combined strategy based on hypotonic lysis isolation and further purification on minicolumns is described here, allowing detection of high molecular weight proteins (i.e. spectrin, ankyrin) and well-resolved 2-DE patterns. An aliquot of the membrane fraction was also in solution digested and analyzed by nano-LC coupled to an LTQ-Orbitrap mass spectrometer. A total of 188 unique proteins were identified by this approach. This study sets the basis for future clinical studies where the erythrocyte cell may be implicated.

Alkalinization potentiates vascular calcium deposition in an uremic milieu.

BACKGROUND: Vascular calcification is a serious complication of chronic kidney disease. Acid-base balance is a relevant, albeit somewhat forgotten factor in the regulation of calcium deposition. Hemodialysis patients undergo repeated episodes of alkaline loading from the dialysate, resulting in prolonged alkalinization. We have hypothesized that extracellular alkalinization may promote vascular calcification. METHODS: Primary cultures of vascular smooth muscle cells were induced to calcify by the phosphate donor beta-glycerophosphate, in the presence of normal or uremic sera from hemodialysis patients and at different pH conditions. The influence of sodium bicarbonate supplementation for 2 months on aorta calcification was studied in 5/6 nephrectomized uremic rats. RESULTS: Uremic serum increased vascular smooth muscle cell calcification (twofold over nonuremic human serum at day 12, p<0.001). Alkalinization of the extracellular medium also increased vascular smooth muscle cell calcification. Increasing the extracellular pH from 7.42 to 7.53 resulted in a 2.5-fold increase in calcium accumulation at day 12 (p<0.05). In vivo, arterial calcification was significantly higher in alkalinized uremic animals (aorta calcification index, uremic + sodium bicarbonate, 164 +/- 57 units, vs. uremic + vehicle, 56 +/- 14 units; p<0.01). CONCLUSIONS: Alkalinization increases vascular calcification in cultured cells and uremic rats. These data may be used to optimize dialysate composition and the degree of alkalinization in calcification-prone individuals with advanced renal disease.

TRPC6 mutational analysis in a large cohort of patients with focal segmental glomerulosclerosis.

BACKGROUND: Mutations in the TRPC6 gene have been reported in six families with adult-onset (17-57 years) autosomal dominant focal segmental glomerulosclerosis (FSGS). Electrophysiology studies confirmed augmented calcium influx only in three of these six TRPC6 mutations. To date, the role of TRPC6 in childhood and adulthood non-familial forms is unknown. METHODS: TRPC6 mutation analysis was performed by direct sequencing in 130 Spanish patients from 115 unrelated families with FSGS. An in silico scoring matrix was developed to evaluate the pathogenicity of amino acid substitutions, by using the bio-physical and bio-chemical differences between wild-type and mutant amino acid, the evolutionary conservation of the amino acid residue in orthologues, homologues and defined domains, with the addition of contextual information. RESULTS: Three new missense substitutions were identified in two clinically non-familial cases and in one familial case. The analysis by means of this scoring system allowed us to classify these variants as likely pathogenic mutations. One of them was detected in a female patient with unusual clinical features: mesangial proliferative FSGS in childhood (7 years) and partial response to immunosupressive therapy (CsA + MMF). Asymptomatic carriers of this likely mutation were found within her family. CONCLUSIONS: We describe for the first time TRPC6 mutations in children and adults with non-familial FSGS. It seems that TRPC6 is a gene with a very variable penetrance that may contribute to glomerular diseases in a multi-hit setting.

Inhibition of JAK2 protects renal endothelial and epithelial cells from oxidative stress and cyclosporin A toxicity.

Cyclosporin A is an immunosuppressant drug widely used in solid organ transplantation, but it has nephrotoxic properties that promote oxidative stress. The JAK2/STAT pathway has been implicated in both cell protection and cell injury; therefore, we determined a role of JAK2 in oxidative stress-mediated renal cell injury using pathophysiologically relevant oxidative challenges. The AG490 JAK2 inhibitor and overexpression of a dominant negative JAK2 protein protected endothelial and renal epithelial cells in culture against peroxide, superoxide anion and cyclosporin A induced cell death while reducing intracellular oxidation in cells challenged with peroxide and cyclosporin A. The decrease in Bcl2 expression and caspase 3 activation, induced by oxidative stress, was prevented by AG490. In mouse models of ischemia/reperfusion and cyclosporin A nephrotoxicity, AG490 decreased peritubular capillary and tubular cell injury. Our study shows that JAK2 inhibition is a promising renoprotective strategy defending endothelial and tubular cells from cyclosporin A- and oxidative stress-induced death.

Hyperphosphatemia and hyperparathyroidism in incident chronic kidney disease patients.

UNLABELLED: Disturbances in bone and mineral metabolism are common in chronic kidney disease (CKD) patients. Most studies have been performed in hemodialysis and there is less information on non-dialysis patients, on the coexistence of other risk factors and on the achievement of more recent and stringent guidelines. Cross sectional study of analytical mineral and bone parameters in 125 incident patients (creatinine clearance <60 ml/min) in a monographic CKD clinic. Evaluation after one year of follow-up in 69 patients. Progression of CKD was associated with significant increased levels of phosphate, calcium x phosphate and iPTH and decreased calcium and 1,25 dihydroxyvitamin D. Levels of 25-hydroxyvitamin D were unchanged, but lower than recommended. Phosphate correlated negatively with 1,25-dihydroxivitamin D and creatinine clearance, and positively with iPTH. At every stage of CKD, most patients had PTH values outside recommended limits. More than 69% CKD 3 and CKD 4 patients had higher than recommended PTH levels. Above recommended phosphate levels were present in 25% of CKD 4 and 47% of CKD 5 patients. Most of these had associated high LDL-cholesterol. Higher than recommended calcium levels were more prevalent than low calcium and there was a high prevalence (31%) of vascular calcification. One year of intervention improved the percentage of patients with controlled calcium or iPTH, but not phosphate. CONCLUSIONS: In incident CKD patients there is a high prevalence of out-of-target mineral and bone analytical parameters. The currently authorized therapeutic arsenal for these patients may not be adequate to deal with the problem.

Cholesterol embolism evaluated by polarized light microscopy after primary renal artery stent placement with filter protection.

PURPOSE: Cholesterol microembolization may explain some treatment failures after renal artery stent placement. The identification of cholesterol crystals may provide significant help in diagnosing the real frequency and severity of this complication. The aim of the present study was to examine the efficacy of polarized light imaging in the detection of cholesterol emboli trapped in a protection device. MATERIALS AND METHODS: During a period of 18 months, 15 significant atherosclerotic stenoses of the ostium of the main renal artery were treated with primary stent placement with embolic protection. The filter device used was made of polyurethane, with a pore size of 115 ?m. The device was mounted over a 0.014-inch guide wire. For pathologic analysis, the recaptured filter basket was compressed between two slides and examined in a microscope under polarized light. RESULTS: All the stenoses were successfully treated without clinical complications. All the filters were deployed and recaptured without difficulty. Cholesterol crystals were detected in 12 filters and no cholesterol was found in three. In one case, trouble with filter manipulation precluded pathologic analysis. No worsening of renal function was detected in any patient during follow-up. CONCLUSIONS: Microscopic analysis with polarized light easily detects the cholesterol crystals trapped in the filter device. This provides evidence that renal cholesterol microembolism is highly prevalent during renal artery stent placement.

Induction of hypoxia-inducible factor 1alpha gene expression by vascular endothelial growth factor.

Transcriptional regulation of vascular endothelial growth factor (VEGF) is critically dependent on hypoxia-inducible factor 1 (HIF-1). However, not only hypoxia, but selected growth factors can induce HIF-1. High levels of both VEGF and HIF-1 coexist in certain conditions, e.g. tumors. Nonetheless, the possibility that the stimulatory relationship between HIF-1 and VEGF may be bi-directional has not been addressed up to date. The present study in endothelial cells analyzed whether HIF-1 is regulated by a product of its own transcriptionally activated genes, namely, VEGF. As a main finding, VEGF-A(165) induced the increase of HIF-1alpha mRNA and HIF-1alpha protein and nuclear translocation. Autologous endothelial cell VEGF mRNA and protein were also increased upon exposure to exogenous VEGF. The signaling implication of reactive oxygen species was examined by comparison with H(2)O(2) and hypoxanthine/xanthine oxidase and by the superoxide dismutase mimetic, MnTMPyP, the Rac1-NAD(P)H oxidase complex inhibitor, apocynin, transfection of a dominant negative Rac1 mutant, and transfection of a p67phox antisense oligonucleotide. Superoxide anion, largely dependent on Rac1-NAD(P)H oxidase complex activity, was the critical signaling element. The transductional functionality of the pathway was confirmed by means of a reporter gene flanked by a transcription site-related VEGF sequence and by quantitative PCR. In summary, the present results reveal a previously undescribed action of VEGF on the expression of its own transcription factor, HIF-1, and on VEGF itself. This effect is principally mediated by superoxide anion, therefore identifying a new, potentially relevant role of reactive oxygen species in VEGF signaling.

Actitudes ante la anemia en la insuficiencia cardíaca. Resultados de una encuesta en España / Anemia in heart failure. Results of a Spanish survey

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[Systemic and renal effects of preventing contrast nephrotoxicity with isotonic (0.9%) and hypotonic (0.45%) saline]. / Efectos renales y sistémicos en la prevención de la nefrotoxicidad por contraste con sueros salino (0,9%) e hiposalino (0,45%).

INTRODUCTION AND OBJECTIVES: Physiological and hypotonic saline solutions have been used interchangeably for preventing contrast media nephrotoxicity. No analysis of the possible differential effects of the two solutions on the milieu interieur or intercompartmental fluid volumes has been performed. Our aim was to study the systemic and renal effects of two types of saline solution regularly used to prevent contrast media nephrotoxicity in patients undergoing coronary angiography. METHODS: Changes in electrolyte levels and volume distribution were studied in 71 individuals who were randomized to receive either 0.9% isotonic saline (n=36) or 0.45% hypotonic saline (n=35) during the 12 hours before and after contrast injection (2000 mL in each period). RESULTS: The creatinine level was elevated equally often in the isotonic and hypotonic saline groups. Isotonic saline administration led to reductions in hemoglobin level, hematocrit and plasma albumin level, and to increases in plasma volume, by 12.3% and 10.4% at 24 and 48 hours, respectively. These changes were significant compared with baseline measurements and compared with the group that received hypotonic saline. Neither of the two saline solutions resulted in a change in plasma atrial natriuretic peptide level. Plasma and urine osmolality decreased only with hypotonic saline. The increase in plasma creatinine level was similar with both isotonic and hypotonic saline. CONCLUSIONS: During standard therapy for preventing contrast media nephrotoxicity, (1) isotonic saline, but not hypotonic saline, increased plasma volume; (2) this increase did not raise the atrial natriuretic peptide level; and (3) no difference in the increase in serum creatinine level was observed between the two saline solutions. These findings provide evidence that 0.45% saline, at a dose suitable for preventing contrast media nephrotoxicity, is associated with a lower risk of volume expansion. This result is important for patients with severely impaired ventricular function.

Efectos renales y sistémicos en la prevención de la nefrotoxicidad por contraste con sueros salino (0.9%) e hiposalino (0.45%) / Systemic and renal effects of preventing contrast nephrotoxicity with isotonic (0.9%) and hypotonic (0.45%) saline

Introducción y objetivos. En la prevención de nefrotoxicidad por contraste se han empleado indistintamente suero salino fisiológico o hiposalino, sin analizarse las posibles diferencias de efecto en el medio interno y la distribución compartimental de volumen. Se estudiaron los efectos renales y sistémicos de dos tipos de suero salino, empleados según pauta de prevención de nefrotoxicidad por contraste en coronariografía. Métodos. Se estudiaron aspectos hidroelectrolíticos y de distribución de volumen en 71 individuos, aleatorizados a recibir suero salino isotónico al 0,9% (n = 36) o suero hiposalino al 0,45% (n = 35), durante las 12 h previas y las 12 h tras el contraste (2.000 ml en cada período). Resultados. La incidencia de elevación de creatinina en el grupo salino fue igual que en el hiposalino. El suero salino causó reducción en los valores de hemoglobina, hematocrito y albúmina plasmática, y un incremento del volumen plasmático (el 12,3 y el 10,4%, a las 24 y a las 48 h); estos cambios fueron significativos con respecto al estado basal y al grupo con suero hiposalino. Sin embargo, los sueros administrados no produjeron elevación del péptido natriurético auricular. Las osmolalidades plasmática y urinaria descendieron sólo con el suero hiposalino. Las elevaciones de creatinina plasmática fueron similares con el suero salino y con el hiposalino. Conclusiones. En una pauta preventiva estándar de la nefrotoxicidad por contraste: a) el suero salino, pero no el hiposalino, aumenta el volumen plasmático; b) este aumento no incrementa la concentración de péptido natriurético auricular, y c) no se ha detectado diferencias entre los sueros en la elevación de creatinina sérica. Estos resultados aportan evidencia de que el suero hiposalino, a la dosis preventiva de nefrotoxicidad por contraste, implica menos riesgo de expansión. Este dato es relevante en pacientes con función ventricular críticamente afectada (AU)

Introduction and objectives. Physiological and hypotonic saline solutions have been used interchangeably for preventing contrast media nephrotoxicity. No analysis of the possible differential effects of the two solutions on the milieu interieur or intercompartmental fluid volumes has been performed. Our aim was to study the systemic and renal effects of two types of saline solution regularly used to prevent contrast media nephrotoxicity in patients undergoing coronary angiography. Methods. Changes in electrolyte levels and volume distribution were studied in 71 individuals who were randomized to receive either 0.9% isotonic saline (n=36) or 0.45% hypotonic saline (n=35) during the 12 hours before and after contrast injection (2000 mL in each period). Results. The creatinine level was elevated equally often in the isotonic and hypotonic saline groups. Isotonic saline administration led to reductions in hemoglobin level, hematocrit and plasma albumin level, and to increases in plasma volume, by 12.3% and 10.4% at 24 and 48 hours, respectively. These changes were significant compared with baseline measurements and compared with the group that received hypotonic saline. Neither of the two saline solutions resulted in a change in plasma atrial natriuretic peptide level. Plasma and urine osmolality decreased only with hypotonic saline. The increase in plasma creatinine level was similar with both isotonic and hypotonic saline. Conclusions. During standard therapy for preventing contrast media nephrotoxicity, (1) isotonic saline, but not hypotonic saline, increased plasma volume; (2) this increase did not raise the atrial natriuretic peptide level; and (3) no difference in the increase in serum creatinine level was observed between the two saline solutions. These findings provide evidence that 0.45% saline, at a dose suitable for preventing contrast media nephrotoxicity, is associated with a lower risk of volume expansion. This result is important for patients with severely impaired ventricular function (AU)

[Anemia in heart failure: pathophysiology, pathogenesis, treatment, and incognitae]. / Anemia en la insuficiencia cardiaca: fisiopatología, patogenia, tratamiento e incógnitas.

Although anemia now occupies an important place in our present understanding of the pathogenesis of heart failure, the condition is surrounded in mystery. Anemia is highly prevalent in patients with heart failure and is of great clinical significance. However, the treatment targets for anemia in patients with heart failure have still not been accurately defined. The present article reviews of the clinical and pathophysiological characteristics of anemia in this context. Particular emphasis has been placed on cellular and molecular regulatory mechanisms, and their implications for treatment.

Anemia en la insuficiencia cardiaca: fisiopatología, patogenia, tratamiento e incógnitas / Anemia in heart failure: pathophysiology, pathogenesis, treatment, and incognitae

Aunque la anemia ha pasado a ocupar un plano relevante en la concepción patogénica actual de la insuficiencia cardiaca (IC), se trata aún de una entidad rodeada de incógnitas. La prevalencia de anemia y su importancia clínica en la población con IC son muy elevadas. Sin embargo, no se han establecido aún con certeza suficiente los objetivos de tratamiento de la anemia en la población con IC. El presente trabajo revisa aspectos clínicos y fisiopatológicos de esta forma particular de anemia, con especial atención a los mecanismos celulares y moleculares de regulación, y sus implicaciones en el tratamiento (AU)

Although anemia now occupies an important place in our present understanding of the pathogenesis of heart failure, the condition is surrounded in mystery. Anemia is highly prevalent in patients with heart failure and is of great clinical significance. However, the treatment targets for anemia in patients with heart failure have still not been accurately defined. The present article reviews of the clinical and pathophysiological characteristics of anemia in this context. Particular emphasis has been placed on cellular and molecular regulatory mechanisms, and their implications for treatment (AU)

Endovascular repair of mycotic aneurysms of the aorta: an alternative to conventional bypass surgery in patients with acute sepsis.

Treatment of mycotic aneurysms of the aorta includes excision of infected tissue followed by anatomic or extra-anatomic bypass. However, operative mortality remains high particularly in elderly patients with comorbidities. We describe here 2 patients with mycotic aneurysms of the descending aorta in whom endovascular repair was successfully performed. In 1 of these patients, stent grafting was attained during the acute, bacteraemic phase of infection. After 12 and 20 months, respectively, of diagnosis, both patients are doing well.

Mechanisms of endothelial cell protection by blockade of the JAK2 pathway.

Inhibition of the JAK2/STAT pathway has been implicated recently in cytoprotective mechanisms in both vascular smooth muscle cells and astrocytes. The advent of JAK2-specific inhibitors provides a practical tool for the study of this pathway in different cellular types. An interest in finding methods to improve endothelial cell (EC) resistance to injury led us to examine the effect of JAK2/STAT inhibition on EC protection. Furthermore, the signaling pathways involved in JAK2/STAT inhibition-related actions were examined. Our results reveal, for the first time, that blockade of JAK2 with the tyrosine kinase inhibitor AG490 strongly protects cultured EC against cell detachment-dependent death and serum deprivation and increases reseeding efficiency. Confirmation of the specificity of the effects of JAK2 inhibition was attained by finding protective effects on transfection with a dominant negative JAK2. Furthermore, AG490 blocked serum deprivation-induced phosphorylation of JAK2. In terms of mechanism, treatment with AG490 induces several relevant responses, both in monolayer and detached cells. These mechanisms include the following: 1) Increase and nuclear translocation of the active, dephosphorylated form of beta-catenin. In functional terms, this translocation is transcriptionally active, and its protective effect is further supported by the stimulation of EC cytoprotection by transfectionally induced excess of beta-catenin. 2) Increase of platelet endothelial cell adhesion molecule (PECAM)/CD31 levels. 3) Increase in total and phosphorylated AKT. 4) Increase in phosphorylated glycogen synthase kinase (GSK)3alpha/beta. The present findings imply potential practical applications of JAK2 inhibition on EC. These applications affect not only EC in the monolayer but also circulating detached cells and involve mechanistic interactions not previously described.

Plasma amyloid-beta, Abeta1-42, load is reduced by haemodialysis.

Patients with chronic renal failure treated with haemodialysis have vascular risk factors that, in the general population, are associated with increased prevalence of Alzheimer's disease (AD). Patients in haemodialysis, however, present different kinds of dementia but they do not have an increased risk of AD. We have hypothesized that amyloid-beta (Abeta)1-42 is washed out from plasma during the dialysis and that this procedure enhances Abeta elimination and reduces the risk of AD. We have measured plasma Abeta1-42 levels in 11 patients with renal failure, before and after haemodialysis. A single procedure reduced the plasma Abeta levels in all subjects with a mean decrement of 30% of baseline. Since Abeta deposition could be altered by certain metals like Cu and Zn, we have also measured the effects of dialysis on the levels of these ions in plasma. We found no changes in levels of Cu and Zn after dialysis. Haemodialysis, therefore, reduces very effectively plasma Abeta without modifying Cu and Zn levels. The potential use of this strategy in patients with AD requires further investigation.