Possible Involvement of Endothelin Peptides and L-Arginine-Nitric Oxide Pathway on the Effect of Endotoxin in the Rabbit Isolated Perfused Kidney

Escherichia coli endotoxin (LPS) when infused through the renal artery of the rabbit isolated perfused kidney prepared as constant pressure mode, caused a decrease in flow rate and kidney weight indicating its primary vasoconstrictor effect. This effect was predominant in kidneys from rabbits pretreated with LPS. Endothelin-1 at a concentration of 10−10 M and big endothelin-1 at a concentration of 10−8 M produced equal vasoconstrictor effects in kidney. Addition of endotheHn converting enzyme inhibitor, phosphoramidon, to the perfusion medium at a concentration of 10−6 M caused a reduction in the effects of both LPS and big ET-1 without altering the vasoconstrictor effect of ETol. However, addition of methylene blue (10−5 M), a soluble guanylate cyclase inhibitor and NG-nitro-L-arginine-methyl ester (10−6 M) to the perfusion medium caused a potentiation in the vasoconstrictor effect of LPS. Indomethacin at a concentration of 10−6 M did not alter the effect of LPS. These results were taken as evidence for the participation of endothelin peptides and the L-arginine-nitric oxide pathway in the effect ofLPS in rabbit isolated perfused kidney

An applied endogenous growth model with human and knowledge capital accumulation for the Turkish economy

We analytically investigate and assess the interactions between knowledge-driven growth, acquisition of human capital, and the role of strategic public policy for the Turkish economy within the context of a general equilibrium model. The model aims to investigate the public policies toward fostering the development of human capital (such as investments in education and learning) and those at enhancing total factor productivity through investments in physical capital and innovation (such as subsidies to R&D), and to study the impact of various public policies on patterns of growth, along with their likely consequences from the points of view of capital accumulation, income distribution, social welfare and economic efficiency for the Turkish economy. With the aid of the model, we seek for analytical answers to the following question: for a government constrained with its budgetary requirements, which type of public subsidiziation policies is more conducive for enhancing growth and social welfare: promotion of human capital formation through subsidies to education expenditures, or promotion of new R&D formation through subsidies to R&D investment expenditures? According to the model findings, a single-handed strategy of only subsidizing education expenditures to promote human capital formation falls short of achieving desirable growth performance in the medium to long run. Under the policy of human capital formation promotion, expected growth and welfare results are weak in the medium-to-long run unless increased human capital can upgrade the number of research personnel employed in the R&D development sector. Under these observations, it can be argued that the public policy should be directed to R&D promotion in the medium-to-long run to complement an education promotion program to sustain human capital formation

Consensus Conference: A reappraisal of Gaucher disease - diagnosis and disease management algorithms

6 p.Type 1 (non neuronopathic) Gaucher disease was the first lysosomal storage disorder for which an effective enzyme replacement therapy was developed and it has become a prototype for treatments for related orphan diseases. There are currently four treatment options available to patients with Gaucher disease, nevertheless, almost 25% of type 1 Gaucher patients do not gain timely access to therapy because of delays in diagnosis after the onset of symptoms. Diagnosis of Gaucher disease by enzyme testing is unequivocal, but the rarity of the disease and non-specific and heterogeneous nature of Gaucher disease symptoms may impede consideration of this disease in the differential diagnosis. To help promote timely diagnosis and optimal management of the protean presentations of Gaucher disease, a consensus meeting was convened to develop algorithms for diagnosis and disease management for Gaucher disease

Hematopoietic recovery kinetics predicts for poor CD34+ cell mobilization after cyclophosphamide chemotherapy in multiple myeloma

Autologous stem cell transplantation is an important part of therapy in patients with multiple myeloma. Some patients fail to collect the desired number of stem cells while others require multiple apheresis to reach the desired apheresis target. The aim of this study was to determine the predictive factors and if the hematopoietic kinetics of recovery were predictive for outcome of stem cell mobilization in cyclophosphamide + growth factor (CY-GF) mobilized patients. Three hundred and ninety six consecutive CY-GF mobilization attempts between January 2000 and December 2009 at Mayo Clinic, Rochester, MN were analyzed. Patients were divided into three groups: optimal (>5 x 106 CD34/kg), suboptimal (25 x 106 CD34/kg) and poor (10/mu L predicted for efficiency of collection and the interval between recovery of WBC>1 post-CY to PB CD34+ cells>10 was shorter in the optimal collection groups. These findings suggest that for patients with a PB CD34+ cell count below 10/mu L on Day 13 following CY or 1 day after the WBC>1 x 109/L, addition of plerixafor may be helpful to salvage the mobilization attempt. Am. J. Hematol., 2012. (C) 2011 Wiley Periodicals, Inc

Posaconazole prophylaxis in patients with acute myeloid leukemia: A real life experience from a prospective multicenter observational study

<div><p>Vaginal candidiasis is a common disorder in women of childbearing age, caused primarily by the dimorphic fungus <i>Candida albicans</i>. Since <i>C</i>. <i>albicans</i> is a normal commensal of the vaginal mucosa, a long-standing question is how the fungus switches from being a harmless commensal to a virulent pathogen. Work with human subjects and in mouse disease models suggests that host inflammatory processes drive the onset of symptomatic infection. Fungal cell wall molecules can induce inflammation through activation of epithelial and immune receptors that trigger pro-inflammatory cytokines and chemokines, but pathogenic fungi can evade recognition by masking these molecules. Knowledge about which cell wall epitopes are available for immune recognition during human infection could implicate specific ligands and receptors in the symptoms of vaginal candidiasis. To address this important gap, we directly probed the surface of fungi present in fresh vaginal samples obtained both from women with symptomatic <i>Candida</i> vaginitis and from women that are colonized but asymptomatic. We find that the pro-inflammatory cell wall polysaccharide β-glucan is largely masked from immune recognition, especially on yeast. It is only exposed on a small percentage of hyphal cells, where it tends to co-localize with enhanced levels of chitin. Enhanced β-glucan availability is only found in symptomatic patients with strong neutrophil infiltration, implicating neutrophils as a possible driver of these cell wall changes. This is especially interesting because neutrophils were recently shown to be necessary and sufficient to provoke enhanced β-glucan exposure in <i>C</i>. <i>albicans</i>, accompanied by elevated immune responses. Taken together, our data suggest that the architecture of <i>C</i>. <i>albicans</i> cell wall can be altered by environmental stress during vaginal candidiasis.</p></div