Chronic kidney disease impairs prognosis in electrical storm

Journal of Interventional Cardiac Electrophysiology - The study sought to assess the prognostic impact of chronic kidney disease (CKD) in patients with electrical storm (ES). ES represents a...     

Changes in cell surface antigen expression during hemopoietic differentiation

Human bone marrow cells were separated on a fluorescence activated cell sorter (FACS) according to their binding of a series of monoclonal antibodies; the positive and negative fractions were cloned for erythroid burst and colony-forming units (BFU-E and CFU-E) and myeloid colony-forming units (CFU-GM), and cytocentrifuge slides were prepared for microscopy of maturing precursors. The pattern of antigen expression on hemopoietic progenitor and precursor populations has been established using antibodies defining blood group (A, I/i), HLA- associated (*A, B, C, DR, DC1), lineage specific, and transferrin receptor antigens. Like monomorphic HLA-DR, the antigen defined by monoclonal antibody OKT10 is expressed on the earliest progenitors and lost during differentiation, suggesting a role in interactions regulating the differentiation of these cells. The HLA-linked DC1 determinant, in contrast to HLA-DR, is not expressed at a detectable level on progenitor cells. Although a lineage-specific early antigen has not been identified, the transferrin receptor is expressed on the majority of erythroid progenitors, but only weakly on myeloid progenitors, and may provide an approach to isolating erythroid progenitors. These and earlier studies with monoclonal antibodies against HLA-DR and glycophorin now provide a detailed "map" of antigen expression during hemopoietic differentiation.     

Effect of enteric pacing on intestinal motility and hormone secretion in dogs with short bowel.

The present study was designed to examine the role of electrode position during retrograde pacing in dogs with short bowel syndrome and unsevered intact duodenum. In nine beagle dogs a subtotal resection of the small bowel and jejunoileostomy was performed. In five of these dogs, an isolated blind loop (jejunum) with preserved mesenteric connections was left in situ as an additional place for a stimulation electrode. Small intestinal motility and plasma levels of insulin, glucagon, gastrin, somatostatin, and glucose were examined during pacing of the residual jejunum or the isolated loop, respectively, compared with control experiments in the same dogs without pacing. During pacing of the loop a significant (P less than 0.05-0.01) decrease in the postprandial small intestinal motility index was observed combined with a significant (P less than 0.05) increase in plasma insulin levels, whereas the postprandial increase in glucagon, somatostatin, gastrin, and glucose levels was not different from that in controls. In contrast, pacing of the jejunum increased postprandial small intestinal motility index (less than or equal to 68%), whereas the levels of the four hormones and plasma glucose were not different from those in controls. The data suggest that in dogs with intact duodenum, pacing on an excluded loop is required to obtain the desired effect of reduced intestinal motility and improved anabolic pancreatic hormone secretion.     

Vascular dysfunction induced by AGE is mediated by VEGF via mechanisms involving reactive oxygen species, guanylate cyclase, and protein kinase C

OBJECTIVE: These experiments were designed to elucidate mechanisms mediating vascular dysfunction induced by advanced glycation end products (AGEs). METHODS: Skin chambers were mounted on the backs of Sprague-Dawley rats and 1 week later, granulation tissue that formed in the bottom of the chamber was exposed twice daily for 7 days to glycated rat serum albumin in the presence and absence of inhibitors of reactive oxygen intermediates, nitric oxide synthase and guanylate cyclase, protein kinase C (PKC), and a neutralizing vascular endothelial growth factor (VEGF) antibody. Vascular (125)I-albumin clearance and blood flow were quantified by use of a double isotope-dilution technique and radiolabeled microspheres, respectively. RESULTS: Albumin permeation and blood flow were increased dose-dependently to a maximum of 2 to 3 times controls by increasing the extent of glucose modification, the concentration, or the duration of exposure to glycated albumin. These increases were significantly attenuated by probucol and superoxide dismutase; N(G)-nitro-L-arginine-methyl ester (L-NAME), a nitric oxide synthase inhibitor; LY83583, a guanylate cyclase inhibitor; and LY333531, a beta-isoform-selective protein kinase C inhibitor. A neutralizing VEGF monoclonal antibody also markedly attenuated the permeability and blood flow increases induced by glycated albumin. CONCLUSIONS: These observations indicate potentially important roles for oxygen free-radicals and nitric oxide in mediating permeability and blood flow changes induced by glycated proteins via mechanisms involving increased protein kinase C activity and VEGF production. Striking similarities in the mechanism by which hyperglycemia and glycated proteins induce vascular dysfunction suggest that a common pathway mediates effects of these different metabolic imbalances on vascular dysfunction.     

Comparative study of the corrosion behavior of peripheral stents in an accelerated corrosion model: experimental in vitro study of 28 metallic vascular endoprostheses

PURPOSE

Clinical cases of stent-fractures show that corrosion behavior might play a role in these fractures. Implanted in vivo, especially in combination with other implanted foreign materials, these metallic products are exposed to special conditions, which can cause a process of corrosion. Here, we aimed to test the corrosion potential of stents made of different materials in an in vitro setting.

METHODS

A total of 28 peripheral stents of different materials (nitinol, cobalt-chromium-nickel, tantalum, V4A) and surface treatments (electropolish, mechanical polish, no polish) were tested in vitro. Corrosion was accelerated by applying a constant voltage of 3.5 V and amperage of 1.16 mA in 0.9% NaCl.

RESULTS

Nitinol stents showed the lowest susceptibility to corrosion and the longest period without damage. The Memotherm II^® (BARD Angiomed^®) was the only stent that showed neither macroscopic nor microscopic damages. The worst performing material was cobalt-chromium-nickel, which showed corrosion damages about ten times earlier compared to nitinol. Considering the reasons for termination of the test, nitinol stents primarily showed length deficits, while V4A and tantalum stents showed fractures. Cobalt-chromium-nickel stents had multiple fractures or a complete lysis in equal proportions. When placed in direct contact, nitinol stents showed best corrosion resistance, regardless of what material they were combined with. In terms of polishing treatments, electropolished stents performed the best, mechanical-polished stents and those without polishing treatment followed.

CONCLUSION

The analysis of corrosion behavior may be useful to select the right stent fulfilling the individual needs of the patient within a large number of different stents.Congenital stenosis or volume decreasing processes due to accumulation of tissues or by outside pressures are the most common indications for vascular interventional therapies. After the initial “cardiac catheterization” by Forssmann et al. (1) in 1929, percutaneous interventional techniques for treatment of vasoconstricting processes was continued constantly, whereby the use of permanent mechanical stents has gained an increasingly important role.Stents used in clinical practice should fulfill certain conditions to achieve an un-problematic application as well as an optimal result. The following properties apply to this ideal: good biocompatibility, low shortening, high-density in X-ray, high patency rates, low thrombogenicity, rapid endothelialization without excessive intimal hyperplasia, high flexibility and longitudinal elasticity, sufficient pressure stability at high centrifugal force, technical ability to secure application and exact positioning, and good expansion ratio for safe percutaneous application also with larger prostheses (2, 3). With the approval of stents for clinical use in 1986, the use of stents in peripheral vessels was also practiced on human patients. Palmaz et al. (4) published the first results of the clinical use in 1988 in one of the first multicenter trials on the use of stents in stenosed atherosclerotic iliac arteries. After the successful development of Palmaz^® stents and Wallstents^® as prototypes of balloon-expandable and self-expanding stents, a variety of new stents have been developed.The stents used today are made of different materials. These include nickel titanium alloys (nitinol), surgical stainless steel (V4A), tantalum, and cobalt compounds. Implanted in the human body, especially in combination with other implanted foreign materials, these metallic products are exposed to special conditions causing a process of corrosion. The higher the ionic conductivity of a liquid is, the faster the reaction. For this reason, liquids that contain a high proportion of electrolytes, such as blood with its high proportion of NaCl, cause much faster corrosion of materials (5).We aimed to perform a comparative study regarding the corrosion behavior of peripheral stents, to reffect the behavior of implanted stents in patients and contribute to find a safer indication in the selection of vascular prostheses. Likewise, we tested the hypothesis that the polishing process influences their corrosion behavior.     

Murine B7 antigen provides an efficient costimulatory signal for activation of murine T lymphocytes via the T-cell receptor/CD3 complex.

We demonstrate that the murine B7 (mB7) protein is a potent costimulatory molecule for the activation of resting murine CD4+ T cells through the T-cell receptor (TCR)/CD3 complex. Stable mB7-transfected Chinese hamster ovary cells, but not vector-transfected controls, synergize with anti-CD3 monoclonal antibody and Con A-induced T-cell activation, resulting ultimately in proliferation. mB7 exerted its effect by inducing production of interleukin 2 and expression of the interleukin 2 receptor. Thus, mB7 costimulates T-cell activation through the TCR/CD3 complex by positively modulating the normal pathway of T-cell expansion. In contrast to the pronounced effect of mB7 on the activation of T cells through the TCR/CD3 complex, the mB7-transfected CHO cell line costimulated T-cell activation via the glycosylphosphatidylinositol-anchored proteins Thy-1 and Ly-6A.2 only inefficiently. Finally, the combination of a calcium ionophore and mB7 is not sufficient to cause T-cell proliferation, while the combination of a calcium ionophore and phorbol 12-myristate 13-acetate (PMA) stimulates T cells efficiently. The signals that mB7 and PMA provide for murine T lymphocyte activation are therefore not interchangeable, although both costimulate activation through the TCR/CD3 complex.     

Antiviral efficacy of NS3-serine protease inhibitor BILN-2061 in patients with chronic genotype 2 and 3 hepatitis C

BILN-2061, a specific and potent peptidomimetic inhibitor of the HCV NS3 protease, has recently been shown to markedly lower serum hepatitis C virus (HCV)-RNA levels in patients chronically infected with HCV genotype 1 in three 2-day proof of principle studies. The aim of the current study was to assess the antiviral efficacy of BILN-2061 in patients with genotypes 2 and 3 HCV infection. The antiviral efficacy, pharmacokinetics, and tolerability of 500 mg twice-daily BILN-2061 given as monotherapy for 2 days in 10 patients chronically infected with non-genotype 1 HCV (genotype 2: n = 3; genotype 3: n =7) and minimal liver fibrosis (Ishak score 0-2) were assessed in a placebo-controlled (placebo n = 2), double-blind pilot study. HCV-RNA levels decreased by > or =1 log(10) copies/mL in 4 of 8 patients treated with BILN-2061. One patient showed a weak response of <1 log(10) copies/mL. Three of 8 treated patients showed no response. There was no correlation between baseline viral concentration or genotype and response. BILN-2061 exhibited good systemic exposure after oral administration and was well tolerated. In conclusion, the antiviral efficacy of the HCV serine protease inhibitor BILN-2061 is less pronounced and more variable in patients with HCV genotype 2 or 3 infection compared with previous results in patients with HCV genotype 1. A lower affinity of BILN-2061 for the NS3 protease of genotypes 2 and 3 HCV is most likely a major contributor to these findings.     

Sphingomyelinase-Like Phosphodiesterase 3b Expression Levels Determine Podocyte Injury Phenotypes in Glomerular Disease

Diabetic kidney disease (DKD) is the most common cause of ESRD in the United States. Podocyte injury is an important feature of DKD that is likely to be caused by circulating factors other than glucose. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating factor found to be elevated in the serum of patients with FSGS and causes podocyte αVβ₃ integrin-dependent migration in vitro. Furthermore, αVβ₃ integrin activation occurs in association with decreased podocyte-specific expression of acid sphingomyelinase-like phosphodiesterase 3b (SMPDL3b) in kidney biopsy specimens from patients with FSGS. However, whether suPAR-dependent αVβ₃ integrin activation occurs in diseases other than FSGS and whether there is a direct link between circulating suPAR levels and SMPDL3b expression in podocytes remain to be established. Our data indicate that serum suPAR levels are also elevated in patients with DKD. However, unlike in FSGS, SMPDL3b expression was increased in glomeruli from patients with DKD and DKD sera-treated human podocytes, where it prevented αVβ₃ integrin activation by its interaction with suPAR and led to increased RhoA activity, rendering podocytes more susceptible to apoptosis. In vivo, inhibition of acid sphingomyelinase reduced proteinuria in experimental DKD but not FSGS, indicating that SMPDL3b expression levels determined the podocyte injury phenotype. These observations suggest that SMPDL3b may be an important modulator of podocyte function by shifting suPAR-mediated podocyte injury from a migratory phenotype to an apoptotic phenotype and that it represents a novel therapeutic glomerular disease target.     

Relation of coronary calcium scores by electron beam tomography to obstructive disease in 2,115 symptomatic patients

This angiographically correlated study reports on, for the first time, age- and gender-based distribution of the volumetric calcium score in a large group of patients with suspected coronary artery disease. Volumetric calcium data predicted significant coronary artery disease (>/=50% lumen diameter stenosis) as well as the traditional Agatston score. Exclusion of any calcium was highly accurate in ruling out obstructive disease in symptomatic subjects >/=50 years of age.