Angiotensin type-2 (AT-2)-receptor activation reduces renal fibrosis in cyclosporine nephropathy: evidence for blood-pressure independent effect

Compound 21 (C21), selective agonist of AT2 receptors, shows antinflammatory effects in hypertension and nephroprotection in diabetes. The aim of this study was to evaluate the effects of C21 in cyclosporine nephropathy, which is characterized mainly by tubulo-interstitial fibrosis. Ten days before and during the experimental periods, low-salt diet was administered to Sprague Dawley rats. Cyclosporine-A (15mg/kg/day, i.p.) and cyclosporine-A plus C21 (0.3 mg/kg /day, i.p) were administered for 1 and 4 weeks. Control groups was left without any treatment. Blood pressure (plethysmographic method) and 24 hour albuminuria were measured once a week. At the end of the experiments, the kidneys were excised for histomorphometric analysis of renal fibrosis and for immunohistochemical evaluation of inflammatory infiltrates and type I and IV collagen expression.After 1 and 4 weeks, the rats treated with cyclosporine showed a significant increase (p <0.01) in blood pressure, no significant changes in albuminuria, a significant increase (p <0.01) in glomerular and tubulo-interstitial fibrosis and inflammatory infiltrates as compared to the control rats. Treatment with C21 did not modify the cyclosporine dependent increase of blood pressure, which was higher than in control rats, but after 4 weeks of treatment significantly reduced (p <0.01) glomerular and tubulo-interstitial fibrosis, type 1 collagen expression and macrophage infiltration, as compared to rats treated with cyclosporine.The administration of C21 showed a protective effect on cyclosporine nephropathy, decreasing renal fibrosis and macrophage infiltration. These data suggest that C21 may counteract tubulo-interstitial fibrosis, the most potent predictor of the progression of renal diseases

Introducing database communication technologies for TED replication in multi-domain networks

In multi-domain transport networks, exchange of Traffic Engineering information is required to enable effective end-to-end service provisioning and restoration by efficiently utilizing network resources. So far, several solutions have been proposed by the communication community such as the Hierarchical Path Computation Element (H-PCE) architecture. Using the H-PCE architecture a parent PCE is responsible for inter-domain path computation, while a dedicated child PCE performs intra-domain path computation within each domain. However, this approach can introduce scalability concerns especially under dynamic traffic condition such as during restoration because all path computation procedures are coordinated by the parent PCE and may require the exchange of many control messages. This paper proposes a standard communication among database systems located at the child PCEs, to exchange and share YANG-based Traffic Engineering information in multi-domain networks. By exploiting currently available database technologies, scalable and predictable performance is demonstrated for both replication mechanisms among child PCEs and information retrieval from the stored databases. Thus, this proposal enables the sharing of intra-domain information at each cPCE that can be locally used, upon failure, to speed-up the recovery procedure

Demonstration of dynamic restoration in segment routing multi-layer SDN networks

Dynamic traffic recovery is designed and validated in a multi-layer network exploiting an SDN-based implementation of Segment Routing. Traffic recovery is locally performed from the node detecting the failure up to the destination node without involving the SDN controller. Experimental results demonstrate recovery time within 50 ms

A Survey on the Path Computation Element (PCE) Architecture

Quality of Service-enabled applications and services rely on Traffic Engineering-based (TE) Label Switched Paths (LSP) established in core networks and controlled by the GMPLS control plane. Path computation process is crucial to achieve the desired TE objective. Its actual effectiveness depends on a number of factors. Mechanisms utilized to update topology and TE information, as well as the latency between path computation and resource reservation, which is typically distributed, may affect path computation efficiency. Moreover, TE visibility is limited in many network scenarios, such as multi-layer, multi-domain and multi-carrier networks, and it may negatively impact resource utilization. The Internet Engineering Task Force (IETF) has promoted the Path Computation Element (PCE) architecture, proposing a dedicated network entity devoted to path computation process. The PCE represents a flexible instrument to overcome visibility and distributed provisioning inefficiencies. Communications between path computation clients (PCC) and PCEs, realized through the PCE Protocol (PCEP), also enable inter-PCE communications offering an attractive way to perform TE-based path computation among cooperating PCEs in multi-layer/domain scenarios, while preserving scalability and confidentiality. This survey presents the state-of-the-art on the PCE architecture for GMPLS-controlled networks carried out by research and standardization community. In this work, packet (i.e., MPLS-TE and MPLS-TP) and wavelength/spectrum (i.e., WSON and SSON) switching capabilities are the considered technological platforms, in which the PCE is shown to achieve a number of evident benefits

Preferential expression of the transcription coactivator HTIF1alpha gene in acute myeloid leukemia and MDS-related AML

HTIF1α, a transcription coactivator which is able to mediate RARα activity and functionally interact with PML, is encoded by a gene on chromosome 7q32–34, which is a critical region in acute myeloid leukemias (AML). With the assumption that this gene may be related to AML, we investigated the HTIF1α DNA structure and RNA expression in leukemic cells from 36 M1–M5 AML patients (28 ‘de novo’ and eight ‘secondary’ to myelodysplastic syndrome (MDS)). Abnormal HTIF1α DNA fragments were never found, whereas loss of HTIF1α DNA was observed in the patients with chromosome 7q32 deletion and translocation, and in one case without detectable chromosome 7 abnormality. HTIF1α RNA was found in acute myelocytic leukemic blasts, and was almost undetectable in normal mononuclear cells. The expression varied among the patients: higher in M1 to M3 subtypes, with the highest values in M1; low levels were constantly observed in M4 and M5 AML. In addition, HTIF1α was significantly overexpressed in MDS-related AML (MDR-AML), but not in MDS. We also found that HTIF1α expression was high in myeloid cell lines. In myeloblastic HL60 and promyelocytic NB4 cells, induced to differentiate along the monocytic–macrophage pathway by TPA or vitamin D3, HTIF1α expression decreased, whereas it was maintained at high levels on induction to granulocytic differentiation by RA or DMSO. In K562 cells, HTIF1α RNA levels did not change after hemin-induced erythroid differentiation. These results suggest that HTIF1α could play a role in myeloid differentiation, being distinctly regulated in hematopoietic lineages

The GRAAL high resolution BGO calorimeter and its energy calibration and monitoring system

We describe the electromagnetic calorimeter built for the GRAAL apparatus at the ESRF. Its monitoring system is presented in detail. Results from tests and the performance obtained during the first GRAAL experiments are given. The energy calibration accuracy and stability reached is a small fraction of the intrinsic detector resolution.Comment: 19 pages, 14 figures, submitted to Nuclear Instruments and Method