The Protective Effects of CD39 Overexpression in Multiple Low-Dose Streptozotocin–Induced Diabetes in Mice

Islet allograft survival limits the long-term success of islet transplantation as a potential curative therapy for type 1 diabetes. A number of factors compromise islet survival, including recurrent diabetes. We investigated whether CD39, an ectonucleotidase that promotes the generation of extracellular adenosine, would mitigate diabetes in the T cell–mediated multiple low-dose streptozotocin (MLDS) model. Mice null for CD39 (CD39KO), wild-type mice (WT), and mice overexpressing CD39 (CD39TG) were subjected to MLDS. Adoptive transfer experiments were performed to delineate the efficacy of tissue-restricted overexpression of CD39. The role of adenosine signaling was examined using mutant mice and pharmacological inhibition. The susceptibility to MLDS-induced diabetes was influenced by the level of expression of CD39. CD39KO mice developed diabetes more rapidly and with higher frequency than WT mice. In contrast, CD39TG mice were protected. CD39 overexpression conferred protection through the activation of adenosine 2A receptor and adenosine 2B receptor. Adoptive transfer experiments indicated that tissue-restricted overexpression of CD39 conferred robust protection, suggesting that this may be a useful strategy to protect islet grafts from T cell–mediated injury

A randomised controlled feasibility trial of an early years language development intervention: results of the ‘outcomes of Talking Together evaluation and results’ (oTTer) project

Background Early language difficulties are associated with poor school readiness and can impact lifelong attainment. The quality of the early home language environment is linked to language outcomes. However, few home-based language interventions have sufficient evidence of effectiveness in improving preschool children’s language abilities. This study reports the first stage in the evaluation of a theory-based programme, Talking Together (developed and delivered by BHT Early Education and Training) given over 6 weeks to families in the home setting. We aimed to test the feasibility and acceptability of delivering Talking Together in the Better Start Bradford community prior to a definitive trial, using a two-armed randomised controlled feasibility study. Methods Families from a single site within the Better Start Bradford reach area were randomly allocated (1:1) to the Talking Together intervention or a wait list control group. Child language and parent-level outcome measures were administered before randomisation (baseline), pre-intervention (pre-test), 2 months post-intervention start (post-test), and 6 months post-intervention start (follow-up). Routine monitoring data from families and practitioners were also collected for eligibility, consent, protocol adherence, and attrition rates. Descriptive statistics on the feasibility and reliability of potential outcome measures were analysed alongside qualitative feedback on trial design acceptability. Pre-defined progression-to-trial criteria using a traffic light system were assessed using routine monitoring data. Results Two-hundred and twenty-two families were assessed for eligibility; of these, 164 were eligible. A total of 102 families consented and were randomised (intervention: 52, waitlist control: 50); 68% of families completed outcome measures at 6-month follow-up. Recruitment (eligibility and consent) reached ‘green’ progression criteria; however, adherence reached ‘amber’ and attrition reached ‘red’ criteria. Child- and parent-level data were successfully measured, and the Oxford-CDI was identified as a suitable primary outcome measure for a definitive trial. Qualitative data not only indicated that the procedures were largely acceptable to practitioners and families but also identified areas for improvement in adherence and attrition rates. Conclusions Referral rates indicate that Talking Together is a much-needed service and was positively received by the community. A full trial is feasible with adaptations to improve adherence and reduce attrition

Mitochondrial a kinase anchor proteins in cardiovascular health and disease: a review article on behalf of the Working Group on Cellular and Molecular Biology of the Heart of the Italian Society of Cardiology

Second messenger cyclic adenosine monophosphate (cAMP) has been found to regulate multiple mitochondrial functions, including respiration, dynamics, reactive oxygen species production, cell survival and death through the activation of cAMP-dependent protein kinase A (PKA) and other effectors. Several members of the large family of A kinase anchor proteins (AKAPs) have been previously shown to locally amplify cAMP/PKA signaling to mitochondria, promoting the assembly of signalosomes, regulating multiple cardiac functions under both physiological and pathological conditions. In this review, we will discuss roles and regulation of major mitochondria-targeted AKAPs, along with opportunities and challenges to modulate their functions for translational purposes in the cardiovascular system

Arteriolopatia calcifica uremica: un'entità clinica rara?

Calcific uremic arteriolopathy (Calcyphilaxis): a rare disease? Report of three cases INTRODUCTION: Calcific uremic arteriolopathy (CUA; CALCYPHILAXIS) is a syndrome that occurs prevalently in patients with chronic kidney disease on dialysis. It is characterized by the medial calcification of skin small arteries leading to necrotic lesions. Several risk factors have been identified: obesity, female gender, diabetes mellitus, hyperphosphatemia, inflammation, treatment with vitamin D, calcium-based phosphate binders and warfarin. MATERIALS AND METHODS: We report three cases of CUA observed from October 2011 to September 2014. RESULTS: The mean age at diagnosis was 56 years (range 33-68). Biochemistry showed: mean levels of PTH=1277 pg/ml (range 1000-1696), serum calcium =10.2 mg/dl (range 9.4-11.1), phosphorus=4.5 mg/dl (range 3.4-5.5). All patients were taking vitamin D, two patients were on warfarin therapy. Following actions were undertaken: interruption of calcium-based phosphate binders, vitamin D and warfarin therapy, initiation of cinacalcet and sodium thiosulfate therapy, use of dialysate with lowest available calcium concentration (1.25 mmol/l), Hyperbaric Oxygen Therapy, surgical dressings of skin lesions three times a week. Significant improvement was observed in mean levels of PTH (331 pg/ml, range 200-465), serum calcium (8.3 mg/dl, range 7.4-9.6) and phosphorus (3.4 mg/dl, range 2.6-3.8). In two out of three patients complete healing of ulcerative lesions was obtained. CONCLUSIONS: These cases underline the importance of early diagnosis of CUA especially in patients with concomitant risk factors and careful clinical monitoring, being CUA characterized by a rapid evolution and high mortalit

Simultaneous detection of cucumber mosaic virus, tomato mosaic virus and potato virus Y by flow cytometry

The simultaneous detection is described of cucumber mosaic virus (CMV), potato virus Y (PVY) and tomato mosaic virus (ToMV) by flow cytometry. Extracts from leaves of healthy and CMV or PVY infected plants were incubated with latex particles, each with a diameter of 3 microm. Extracts from ToMV infected or uninfected plants, however, were incubated with particles, each with a diameter of 6 microm. Beads were washed and incubated in succession with primary and secondary antibodies, the latter labeled with phycoerythrin (PE) or fluorescein (FITC). CMV and PVY were distinguished on the basis of the fluorescence emitted by FITC and PE; ToMV was distinguished from CMV and PVY on the basis of the different diameter (6 microm) of the particles on which it was adsorbed. The three viruses were detected also by another approach. Latex particles with a diameter of 3, 6 and 10 microm were separately sensitized with antibodies specific for CMV, PVY and ToMV. An equal number of sensitized particles was mixed and incubated with the plant extracts containing the three viruses and then with anti-CMV, anti-PVY and anti-ToMV antibodies labeled with FITC. The study describes also a virus purification method based on the use of antibody coated latex particles. The method is simple technically and applicable to the purification of large as well as minute amounts of different viruses (CMV, PVY and ToMV)