Renal lesions in patients with type 2 diabetes: A puzzle waiting to be solved

Three hundred sixty-six million people worldwide will be living with diabetes mellitus (DM) by 2030 ([1, 2]; http://www.idf.org/global-diabetes-plan-2011-2021). Prospectively, 75–150 million of these patients will develop a diabetic nephropathy (DN) or a non-diabetic renal disease (NDRD), either isolated or superimposed on DN [3, 4]. To date, the differential diagnosis between ND and NDRD remains a challenge that nephrologists are trying to win [5]

Taxonomy and analysis of IP micro-mobility protocols in single and simultaneous movements scenarios

The micro-mobility is an important aspect in mobile communications, where the applications are anywhere and used anytime. One of the problems of micro-mobility is the hand-off latency. In this paper, we analyse two solutions for IP micro-mobility by means of a general taxonomy. The first one is based on the Stream Control Transmission Protocol (SCTP), which allows the dynamic address configuration of an association. The second one is based on the Session Initiation Protocol (SIP), which is the most popular protocol for multimedia communications over IP networks. We show that for the SCTP solution, there is room for further optimisations of the hand-off latency by adding slight changes to the protocol. However, as full end-to-end solution, SCTP is not able to handle simultaneous movement of hosts, whose probability in general cannot be neglected. On the other hand, the SIP can handle both single and simultaneous movements cases, although the hand-off latency can increase with respect to the SCTP solution. We show that for a correct and fast hand-off, the SIP server should be statefull

Diabetic kidney disease. new clinical and therapeutic issues. Joint position statement of the Italian Diabetes Society and the Italian Society of Nephrology on "the natural history of diabetic kidney disease and treatment of hyperglycemia in patients with type 2 diabetes and impaired renal function"

Recent epidemiological studies have disclosed heterogeneity in diabetic kidney disease (DKD). In addition to the classical albuminuric phenotype, two new phenotypes have emerged, i.e., “nonalbuminuric renal impairment” and “progressive renal decline”, suggesting that DKD progression toward end-stage kidney disease in diabetic patients may occur through two distinct pathways heralded by a progressive increase in albuminuria and decline in renal function independent of albuminuria, respectively. Besides the natural history of DKD, also the management of hyperglycemia in patients with type 2 diabetes and reduced renal function has profoundly changed in the last two decades. New anti-hyperglycemic drugs have become available for treatment of these individuals and the lowest estimated glomerular filtration rate safety thresholds for some of the old agents have been reconsidered. This joint document of the Italian Diabetes Society (SID) and the Italian Society of Nephrology (SIN) reviews the natural history of DKD in the light of the recent epidemiological literature and provides updated recommendations on anti-hyperglycemic treatment with non-insulin agents in DKD patients

ADAM10 Localization in Temporomandibular Joint Disk with Internal Derangement: An Ex Vivo Immunohistochemical Study

The purpose of this study was to determine the presence of ADAM10 in temporomandibular joint disk with internal derangement. Twenty-five paraffin blocks of displaced temporomandibular joint (TMJ) disk specimens from earlier investigations were retrieved from the archives of the University of Catania. Of these 16 had been removed from females and 9 from males; 11 with anterior disk displacement with reduction (ADDwR) and 14 with anterior disk displacement without reduction (ADDwoR). The sections were dehydrated, embedded in paraffin and cut. Then they were incubated in 0.3% H2O2/methanol and half of sections from each sample were incubated in diluted rabbit polyclonal anti-ADAM10 antibody. Then biotinylated anti-mouse/anti-rabbit IgG was applied to the sections, followed by avidin–biotin–perioxidase complex. The results were analyzed and the results were that ADAM10 was overexpressed in the posterior band of sections from patients with ADDwR compared to the other bands of both ADDwR and ADDwoR sections. Overexpression correlated with severe histopathological degeneration. We believe these results have the potential to provide insights into the pathogenesis of TMJ disk degeneration and to help design new therapeutic approaches targeting the proteolytic events that lead to tissue degeneration. Early therapeutic block of ADAM10 activity could succeed in limiting aggrecan-rich matrix breakdown without affecting normal physiology

How far are we from WebRTC-1.0? An update on standards and a look at what's next

Real-time communication between browsers has represented an unprecedented standardization effort involving both the IETF and the W3C. These activities have involved both the real-time protocol suite and the application-level JavaScript APIs to be offered to developers in order to allow them to easily implement interoperable real-time multimedia applications in the web. This article sheds light on the current status of standardization, with special focus on the upcoming final release of the so-called WebRTC-1.0 standard ecosystem. It takes stock of the situation with respect to hot topics such as codecs, session description and stream multiplexing. It also briefly discusses how standard bodies are dealing with seamless integration of the initially competing effort known as “Object Real Time Communications.

Coronary Endothelium‐Dependent Vasomotor Function After Drug‐Eluting Stent and Bioresorbable Scaffold Implantation

Infarto de miocardio; Disfunción endotelial; Tomografía de coherencia ópticaMyocardial infarction; Endothelial dysfunction; Optical coherence tomographyInfart de miocardi; Disfunció endotelial; Tomografia de coherència òpticaBackground Early generation drug‐eluting stents (DESs) showed a high grade of coronary endothelial dysfunction that was attributed to lack of stent reendothelialization. Endothelium‐dependent vasomotor response of current DESs and bioresorbable scaffolds (BRSs) remains unknown. This study sought to assess the device‐related endothelial function of current devices and to correlate neointima healing with endothelial function. Methods and Results A total of 206 patients from 4 randomized trials treated with the durable‐polymer everolimus‐eluting Xience (n=44), bioresorbable‐polymer sirolimus‐eluting Orsiro (n=35), polymer‐free biolimus‐eluting Biofreedom (n=24), bioactive endothelial‐progenitor cell‐capturing sirolimus‐eluting Combo DES (n=25), polymer‐based everolimus‐eluting Absorb (n=44), and Mg‐based sirolimus‐eluting Magmaris BRS (n=34) underwent endothelium‐dependent vasomotor tests and optical coherence tomography imaging, as per protocol, at follow‐up. Crude vasomotor responses of distal segments to low‐dose acetylcholine (10−6 mol/L) were different between groups: bioresorbablepolymer DEShad the worst (−8.4%±12.6%) and durable‐polymer DES had the most physiologic (−0.4%±11.8%; P=0.014). High‐dose acetylcholine (10−4 mol/L) showed similar responses between groups (ranging from −10.8%±11.6% to −18.1%±15.4%; P=0.229). Device healing was different between devices. Uncovered struts ranged from 6.3%±7.1% (bioresorbable‐polymer DES) to 2.5%±4.5% (bioactive DES; P=0.056). In multivariate models, endothelium‐dependent vasomotor response was associated with age, bioresorbable‐polymer DES, and angiographic lumen loss, but not with strut coverage nor plaque type. Endothelial dysfunction (defined as ≥4% vasoconstriction) was observed in 46.6% of patients with low‐dose and 68.9% with high‐dose acetylcholine, without differences between groups. Conclusions At follow‐up, endothelial dysfunction was frequently observed in distal segments treated with current stents without remarkable differences between devices. Although neointima healing was different between devices, poor healing was not associated with endothelial dysfunction.The source funding of the 4 randomized trials included in this study is the following. The BVS‐FLOW trial (Coronary vasomotor function and myocardial flow with bioresorbable vascular scaffolds or everolimus‐eluting metallic stents: a randomised trial) was funded by a grant of “La Marato” Foundation. The Spanish Heart Foundation funded the RE‐TROFI2 (Long‐Term Coronary Functional Assessment of the Infarct‐Related Artery Treated With Everolimus‐Eluting Bioresorbable Scaffolds or Everolimus‐Eluting Metallic Stents: Insights of the TROFI II Trial) and MAGSTEMI (Magnesium‐Based Resorbable Scaffold Versus Permanent Metallic Sirolimus‐Eluting Stent in Patients With ST‐Segment Elevation Myocardial Infarction) trials. The FUNCOMBO (Coronary endothelial and microvascular function distal to polymer‐free and endothelial cell‐capturing drug‐eluting stents) trial was funded by OrbusNeich and was promoted by the Spanish Heart Foundation

Assessment of cryopreserved human tunica albuginea for the surgical treatment of penile defects

Peyronie’s disease, a connective tissue disorder of penile tunica albuginea (TA) associated with penile deformity, curvature, pain and erectile dysfunction, is best managed surgically, but suitable graft biomaterials are not available. To establish whether cryopreservation affects human TA in view of its use in allotransplants. The effects on TA samples of the two most widely used tissue cryopreservation methods were investigated using an ad hoc panel of histochemical, immunohistochemical and ultrastructural tests. Apoptotic cells were evaluated using the TUNEL assay. Assessment of tissue integrity and arrangement of collagen and elastic fibers in thawed TA. Both cryofixation methods provided TA tissue suitable for use as graft material. Significant ultrastructural changes, namely a greater diameter of collagen fibrils, were detected in sections preserved in liquid nitrogen; nonetheless, such increase never exceeded the normal range. The comprehensive panel of assays used proved suitable to characterize the thawed tissue. Human TA is suitable for cryopreservation; freezing at -80 °C provides better results than preservation in liquid nitrogen

Physiological responses of Arundo donax ecotypes to drought: a common garden study

Genetic analyses have suggested that the clonal reproduction of Arundo donax has resulted in low genetic diversity. However, an earlier common garden phenotyping experiment identified specimens of A. donax with contrasting biomass yields (ecotypes 6 and 20). We utilized the same well-established stands to investigate the photosynthetic and stress physiology of the A. donax ecotypes under irrigated and drought conditions. Ecotype 6 produced the largest yields in both treatments. The A. donax ecotypes exhibited identical high leaf-level rates of photosynthesis (PN) and stomatal conductance (Gs) in the well-watered treatment. Soil drying induced reductions in PN and Gs, decreased use of light energy for photochemistry, impaired function of photosystem II and increased heat dissipation similarly in the two ecotypes. Levels of biologically active free-abscisic acid (ABA) and fixed glycosylated-ABA increased earlier in response to the onset of water deficit in ecotype 6; however, as drought progressed, the ecotypes showed similar increases in both forms of ABA. This may suggest that because of the low genetic variability in A. donax the genes responding to drought might have been activated similarly in the two ecotypes, resulting in identical physiological responses to water deficit. Despite the lack of physiological ecotypic differences that could be associated with yield, A. donax retained a high degree of PN and biomass gain under water deficit stress conditions. This may enable utilization of A. donax as a fast growing biomass crop in rain-fed marginal lands in hot drought prone climates

The role of intrinsic pathway in apoptosis activation and progression in Peyronie’s disease

Peyronie’s disease (PD) is a connective tissue disorder where formation of fibrous plaques in tunica albuginea (TA) and erectile tissue can result in penile deformity, pain, and erectile dysfunction. Fibrosis, its major pathological manifestation, arises from fibroblast proliferation and accumulation of extracellular matrix; PD progresses with formation of plaques or even ectopic calcification having the appearance of scar tissue, which prevent TA expansion during erections. The mechanisms underpinning PD are unclear, and relatively little is known about the disease itself. To date corrective surgery is the sole effective treatment. A greater understanding of PD pathophysiology at the molecular level has the potential to help develop novel medical therapeutic approaches. The aim of this study was to investigate the activation of the apoptotic intrinsic apoptotic pathway in plaques from PD patients. Tunica albuginea from either PD and control patients were assessed for the expression of bax, bcl-2, caspase 9 and 3 using immunohistochemistry, and by measurement of apoptotic cells using TUNEL assay. Bax overexpression was observed in metaplasic bone tissue, in fibroblasts and in myofibroblast of plaques from PD patients. Little or no bcl-2 immunostaining was detected in samples from either patients or controls. Caspase 3 immunostaining was very strong in fibrous tissue, in metaplasic bone osteocytes and in primary ossification center osteoblasts. Moderate caspase 9 immunostaining was seen in fibrous cells plaques and in osteocytes and osteoblasts of primary ossification centers from PD patients. Control samples were negative for caspase 9 immunostaining. In PD patients the TUNEL immunoassay showed intense immunostaining of fibroblasts and myofibroblasts, the absence of apoptotic cells in metaplasic bone tissue and on the border between fibrous and metaplasic bone tissue. Apoptotic cell death occurs in stabilized PD plaques and is partly induced by the intrinsic mitochondrial pathway. The present findings can have clinical implications and may help devise improved treatment strategies. A therapeutic approach aimed at enhancing apoptosis-inducing molecules would at least help delay the progression of PD. Identification of target molecules for gene construct or biological or chemical reagent delivery to target sites could contribute to induce PD plaque stabilization

Beneficial effects of PACAP in osteoarthritis cartilage. An “in vivo” and an “in vitro” morphological and biochemical study

Osteoarthritis (OA); the most common form of degenerative joint disease; is associated with variations in pro-inflammatory growth factor levels; inflammation and hypocellularity resulting from chondrocyte apoptosis (1). Pituitary adenylate cyclaseactivating polypeptide (PACAP) is a neuropeptide endowed with a range of trophic effects in several cell types; including chondrocytes (2). However; its role in OA has not been studied. To address this issue; we investigated whether PACAP expression is affected in OA cartilage obtained from experimentally-induced OA rat models; and then studied the effects of PACAP in isolated chondrocytes exposed to IL-1β in vitro to mimic the inflammatory milieu of OA cartilage. OA induction was established by histomorphometric and histochemical analyses. Changes in PACAP distribution in cartilage or its concentration in synovial fluid (SF) were assessed by immunohistochemistry and ELISA. Results showed that PACAP abundance in cartilage tissue and SF was high in healthy controls. OA induction decreased PACAP levels both in affected cartilage and SF. In vitro; PACAP prevented IL-1β-induced chondrocyte apoptosis; as determined by MTT assay; Hoechst staining and western blots of apoptotic-related proteins. These changes were also accompanied by decreased i-NOS and COX-2 levels; suggesting an anti-inflammatory effect. Altogether, these findings support a potential role for PACAP as a chondroprotective agent for the treatment of OA