Antagonism of the prokineticin system prevents and reverses allodynia and inflammation in a mouse model of diabetes

Neuropathic pain is a severe diabetes complication and its treatment is not satisfactory. It is associated with neuroinflammation-related events that participate in pain generation and chronicization. Prokineticins are a new family of chemokines that has emerged as critical players in immune system, inflammation and pain. We investigated the role of prokineticins and their receptors as modulators of neuropathic pain and inflammatory responses in experimental diabetes. In streptozotocin-induced-diabetes in mice, the time course expression of prokineticin and its receptors was evaluated in spinal cord and sciatic nerves, and correlated with mechanical allodynia. Spinal cord and sciatic nerve pro- and anti-inflammatory cytokines were measured as protein and mRNA, and spinal cord GluR subunits expression studied. The effect of preventive and therapeutic treatment with the prokineticin receptor antagonist PC1 on behavioural and biochemical parameters was evaluated. Peripheral immune activation was assessed measuring macrophage and T-helper cytokine production. An up-regulation of the Prokineticin system was present in spinal cord and nerves of diabetic mice, and correlated with allodynia. Therapeutic PC1 reversed allodynia while preventive treatment blocked its development. PC1 normalized prokineticin levels and prevented the up-regulation of GluN2B subunits in the spinal cord. The antagonist restored the pro-/anti-inflammatory cytokine balance altered in spinal cord and nerves and also reduced peripheral immune system activation in diabetic mice, decreasing macrophage proinflammatory cytokines and the T-helper 1 phenotype. The prokineticin system contributes to altered sensitivity in diabetic neuropathy and its inhibition blocked both allodynia and inflammatory events underlying disease

Front-end Electronics and Optimal Ganging Schemes for Single Photon Detection with Large Arrays of SiPMs in Liquid Argon

The operation of large arrays of silicon photomultipliers (SiPM) in tanks of noble liquids requires low noise, low power front-end amplifiers, able to operate reliably in the cryogenic environment. A suitable amplifier needs to be paired with a proper SiPM ganging scheme, meaning the series/parallel combination of SiPMs at its input. This paper presents a simple model to estimate the ganging scheme that gives the best signal to noise ratio once the basic electrical characteristics of the SiPM and amplifier are known. To prove the validity of the model, we used an amplifier based on discrete components, which achieves a white voltage noise in the 0.25-0.37 nV/$\surd$Hz range at liquid nitrogen temperature, while drawing 2-5 mW of power. Combined with the optimal ganging scheme obtained with the model, the amplifier demonstrated excellent single photon sensitivity up to 96 6x6 mm$^2$ SiPMs (total area 34.6 cm$^2$, S/N $\simeq$ 8-11). The measured results are in a good match with calculated values, predicting the possibility to achieve a clear separation of photoelectron peaks also with larger areas

Anticoagulant treatment in patients with pulmonary arterial hypertension associated with systemic sclerosis: More shadows than lights

Pulmonary arterial hypertension is a chronic and progressive disease characterized by elevated pulmonary artery pressure and pulmonary vascular resistance leading to heart failure and premature death. Pulmonary arterial hypertension is characterized by proliferative and obstructive lesions in the distal pulmonary arteries and some descriptions include also thrombotic lesions. Despite this, in an era when multiple effective pulmonary arterial hypertension therapies are available, the role of anticoagulation in the treatment of pulmonary arterial hypertension remains uncertain. In particular, anticoagulant treatment in pulmonary arterial hypertension associated with connective tissue disease seems to be associated with unfavorable risk to benefit ratio due to an increased rate of bleeding from the gastrointestinal tract. However, anticoagulation may be required in conditions with increased thrombophilia like in the presence of lupus anticoagulant phenomenon or in the presence of anticardiolipin antibodies

Tuning the Structure of Nylon 6,6 Electrospun Bundles to Mimic the Mechanical Performance of Tendon Fascicles

Tendon and ligament injuries are triggered by mechanical loading, but the specific mechanisms are not yet clearly identified. It is well established however, that the inflection and transition points in tendon stress-strain curves represent thresholds that may signal the onset of irreversible fibrillar sliding. This phenomenon often results in a progressive macroscopic failure of these tissues. With the aim to simulate and replace tendons, electrospinning has been demonstrated to be a suitable technology to produce nanofibers similar to the collagen fibrils in a mat form. These nanofibrous mats can be easily assembled in higher hierarchical levels to reproduce the whole tissue structure. Despite the fact that several groups have developed electrospun tendon-inspired structures, an investigation of the inflection and transition point mechanics is missing. Comparing their behavior with that of the natural counterpart is important to adequately replicate their behavior at physiological strain levels. To fill this gap, in this work fascicle-inspired electrospun nylon 6,6 bundles were produced with different collector peripheral speeds (i.e., 19.7 m s–1; 13.7 m s–1; 7.9 m s–1), obtaining different patterns of nanofibers alignment. The scanning electron microcopy revealed a fibril-inspired structure of the nanofibers with an orientation at the higher speed similar to those in tendons and ligaments (T/L). A tensile mechanical characterization was carried out showing an elastic-brittle biomimetic behavior for the higher speed bundles with a progressively more ductile behavior at slower speeds. Moreover, for each sample category the transition and the inflection points were defined to study how these points can shift with the nanofiber arrangement and to compare their values with those of tendons. The results of this study will be of extreme interest for the material scientists working in the field, to model and improve the design of their electrospun structures and scaffolds and enable building a new generation of artificial tendons and ligaments

Determination of Free Amino Acids in Milk, Colostrum and Plasma of Swine via Liquid Chromatography with Fluorescence and UV Detection

Amino acids are ubiquitous components of mammalian milk and greatly contribute to its nutritional value. The compositional analysis of free amino acids is poorly reported in the literature even though their determination in the biological fluids of livestock animals is necessary to establish possible nutritional interventions. In the present study, the free amino acid profiles in mature swine milk, colostrum and plasma were assessed using a targeted metabolomics approach. In particular, 20 amino acids were identified and quantified via two alternative and complementary reversed-phase HPLC methods, involving two stationary phases based on core-shell technology, i.e., Kinetex C18 and Kinetex F5, and two detection systems, i.e., a diode array detector (DAD) and a fluorescence detector (FLD). The sample preparation involved a de-proteinization step, followed by pre-chromatographic derivatization with 9-fluorenylmethylchloroformate (FMOC-Cl). The two optimized methods were validated for specificity, linearity, sensitivity, matrix effect, accuracy and precision and the analytical performances were compared. The analytical methods proved to be suitable for free amino acid profiling in different matrices with high sensitivity and specificity. The correlations among amino acid levels in different biological fluids can be useful for the evaluation of physio-pathological status and to monitor the effects of therapeutic or nutritional interventions in humans and animals

Large area Si low-temperature light detectors with Neganov-Luke effect

Next generation calorimetric experiments for the search of rare events rely on the detection of tiny amounts of light (of the order of 20 optical photons) to discriminate and reduce background sources and improve sensitivity. Calorimetric detectors are the simplest solution for photon detection at cryogenic (mK) temperatures. The development of silicon based light detectors with enhanced performance thanks to the use of the Neganov-Luke effect is described. The aim of this research line is the production of high performance detectors with industrial-grade reproducibility and reliability.Comment: 4 pages, 2 figure

Emotional abuse interacts with borderline personality in adolescent inpatients with binge-purging eating disorders

Purpose Childhood abuse is associated with an increased risk of developing eating disorders (EDs) as well as personality disorders (PDs). However, their interaction is still uncertain, particularly in adolescents. This study investigates the correlations between childhood emotional neglect (CEN), childhood emotional abuse (CEA), and obsessive-compulsive and borderline personality styles in female adolescent inpatients with eating disorders (EDs). Methods One hundred and twenty-eight inpatients (ages 14-18) were assessed, 54 were diagnosed with restricting-type anorexia nervosa (AN-R) and 33 with a binge-purging ED [BP-ED; comprising patients with binge-purging type anorexia nervosa (AN-BP), n = 15, and bulimia nervosa (BN), n = 18]. Fifty healthy participants made up the control group (CG). CEN and CEA were assessed with the Childhood Trauma Questionnaire, while the Personality Style and Disorder Inventory was implemented to determine personality styles. Results A MANOVA revealed a significant main effect of CEA on spontaneous-borderline personality style [F(8,119) = 17.1, p < 0.001, η2 = 0.126], as well as a main effect of ED group on spontaneous-borderline [F(2,119) = 3.1, p = 0.048, η2 = 0.050]. A significant interaction between ED group, CEA, and spontaneous-borderline was found [F(2,119) = 3.5, p = 0.034, η2 = 0.055] with BP-ED showing significantly higher scores in CEA (9.3 ± 4.0) and in spontaneous-borderline (14.2 ± 6.2). Conclusions Considering CEA and borderline personality style in adolescent inpatients with BN or AN-BP may help improve the understanding of the etiology and maintenance of BP-ED and provide more effective treatment targets. Level of evidence Level III, case–control analytic study

Apoptotic-induced effects of acacia catechu willd. Extract in human colon cancer cells

The research for innovative treatments against colon adenocarcinomas is still a great challenge. Acacia catechu Willd. heartwood extract (AC) has health-promoting qualities, especially at the gastrointestinal level. This study characterized AC for its catechins content and investigated the apoptosis-enhancing effect in human colorectal adenocarcinoma HT-29 cells, along with its ability to spare healthy tissue. MTT assay was used to describe the time course, concentration dependence and reversibility of AC-mediated cytotoxicity. Cell cycle analysis and AV-PI and DAPI-staining were performed to evaluate apoptosis, together with ROS formation, mitochondrial membrane potential (MMP) changes and caspase activities. Rat ileum and colon rings were tested for their viability and functionality to explore AC effects on healthy tissue. Quantitative analysis highlighted that AC was rich in (\ub1)-catechin (31.5 \ub1 0.82 mg/g) and ( 12)-epicatechin (12.5 \ub1 0.42 mg/g). AC irreversibly decreased cell viability in a concentration-dependent, but not time-dependent fashion. Cytotoxicity was accompanied by increases in apoptotic cells and ROS, a reduction in MMP and increases in caspase-9 and 3 activities. AC did not affect rat ileum and colon rings\u2019 viability and functionality, suggesting a safe profile toward healthy tissue. The present findings outline the potential of AC for colon cancer treatment