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Mara Castelli Giada Amodeo Lucia Negri Roberta Lattanzi Daniela Maftei Cecilia Gotti Francesco Pistillo Valentina Onnis Cenzo Congu Alberto E. Panerai Paola Sacerdote Silvia Franchi 《PloS one》2016,11(1)
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. 相似文献
13.
Clelia Dallanoce Mara Canovi Carlo Matera Tiziana Mennini Marco De Amici Marco Gobbi Carlo De Micheli 《Bioorganic & medicinal chemistry》2012,20(21):6344-6355
A group of spirocyclic tropanyl-Δ2-isoxazolines was synthesized exploiting the 1,3-dipolar cycloaddition of nitrile oxides to olefins. Their interaction with the dopamine and serotonin transporters (DAT and SERT, respectively) was evaluated through binding experiments. The majority of the compounds had no inhibitory effects (IC50 >> 10 μM), while some had an IC50 value in the range 5–10 μM (8a–c, 10b and 11c on DAT, 12b on SERT). Unexpectedly, one of the tertiary amines under investigation, that is 3′-methoxy-8-methyl-spiro{8-azabicyclo[3.2.1]octane-3,5′(4′H)-isoxazole 7a, was able to enhance at a concentration of 10 μM both [3H]citalopram and [3H]paroxetine binding to SERT in rat brain homogenate (up to 25%, due to an increase of Bmax) and [3H]serotonin uptake (up to 30%) in cortical synaptosomes. This peculiar pharmacological profile of 7a suggests it binds to an allosteric site on SERT, and positions derivative 7a as a very useful tool to investigate SERT machinery. 相似文献
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Lúcia Mara J. dos Anjos Pollyanna A. Salvador lvaro C. de Souza Adenilson de Souza da Fonseca Flvia de Paoli Jacy Gameiro 《Journal of biophotonics》2019,12(2)
As low‐level laser therapy immune cells responses are not always clarified, this study aimed to evaluate cytokines and immune cells profile after low‐level laser therapy (LLLT) on arthritis‐induced model. Arthritis was induced in C57BL/6 mice divided into five groups: euthanized 5 hours after inflammation induction; untreated; dexamethasone treated; LLLT at 3 Jcm?2; LLLT at 30 Jcm?2. Cytokine measurements by enzyme‐linked immunosorbent assay and mRNA cytokine relative levels by real‐time quantitative polymerase chain reaction were performed with arthritic ankle (IL‐1β, IL‐6, TNF‐α, IL‐10 and TGF‐β). Macrophages, dendritic cells, natural killer cells, lymphocytes CD4+, CD8+, Treg and costimulatory proteins were quantified in proximal lymph node by flow cytometry. Data showed decrease in all cytokine levels after LLLT and alteration in mRNA relative levels, depending on the energy density used. LLLT was able to increase of immune cell populations analyzed in the lymph node as well as costimulatory proteins expression on macrophages and dendritic cells. Treg TCD4+ and TCD8+ population enrichment were observed in LLLT at 3 and 30 Jcm?2 groups, respectively. Furthermore, Treg TCD8+ cells expressing higher levels of CD25 were observed at LLLT at 30 Jcm?2 group. Our results indicate that LLLT could change the inflammatory course of arthritis, tending to accelerate its resolution through immune cells photobiostimulation. 相似文献
16.
Anna Mara Scandroglio Gabriele Finco Marina Pieri Roberto Ascari Maria Grazia Calabrò Daiana Taddeo Francesca Isella Annalisa Franco Mario Musu Giovanni Landoni Ottavio Alfieri Alberto Zangrillo 《BMC anesthesiology》2015,15(1)
Background
The elderly undergo cardiac surgery more and more frequently, often present multiple comorbidities, assume chronic therapies, and present a unique physiology. Aim of our study was to analyze the experience of a referral cardiac surgery center with all types of cardiac surgery interventions performed in patients ≥80 years old over a six years’ period.Methods
A retrospective observational study performed in a university hospital. 260 patients were included in the study (3.5% of the patients undergoing cardiac surgery in the study period).Results
Mean age was 82 ± 1.8 years. Eighty-five percent of patients underwent elective surgery, 15% unplanned surgery and 4.2% redo surgery. Intervention for aortic valve pathology and coronary artery bypass grafting were performed in 51% and 46% of the patients, respectively. Interventions involving the mitral valve were the 26% of the total, those on the tricuspid valve were 13% and those on the ascending aortic arch the 9.6%. Postoperative low output syndrome was identified in 44 patients (17%). Mortality was 3.9% and most of the patients (91%) were discharged from hospital in good clinical conditions. Hospital mortality was lower in planned vs unplanned surgery: 3.8% vs 14% respectively. Chronic obstructive pulmonary disease (OR 9.106, CI 2.275 – 36.450) was the unique independent predictor of mortality.Conclusions
Clinicians should be aware that cardiac surgery can be safely performed at all ages, that risk stratification is mandatory and that hemodynamic treatment to avoid complications is expected.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2253-15-15) contains supplementary material, which is available to authorized users. 相似文献17.
Laura Grange Cheikh Loucoubar Olivier Telle Adama Tall Joseph Faye Cheikh Sokhna Jean-Fran?ois Trape Anavaj Sakuntabhai Jean-Fran?ois Bureau Richard Paul 《PloS one》2015,10(4)
Malaria transmission intensity is highly heterogeneous even at a very small scale. Implementing targeted intervention in malaria transmission hotspots offers the potential to reduce the burden of disease both locally and in adjacent areas. Transmission of malaria parasites from man to mosquito requires the production of gametocyte stage parasites. Cluster analysis of a 19-year long cohort study for gametocyte carriage revealed spatially defined gametocyte hotspots that occurred during the time when chloroquine was the drug used for clinical case treatment. In addition to known risk factors for gametocyte carriage, notably young age (<15 years old) and associated with a clinical episode, blood groups B and O increased risk compared to groups A and AB. A hotspot of clinical P. falciparum clinical episodes that overlapped the gametocyte hotspots was also identified. Gametocyte positivity was found to be increased in individuals who had been treated with chloroquine, as opposed to other drug treatment regimens, for a clinical P. falciparum episode up to 30 days previously. It seems likely the hotspots were generated by a vicious circle of ineffective treatment of clinical cases and concomitant gametocyte production in a sub-population characterized by an increased prevalence of all the identified risk factors. While rapid access to treatment with an effective anti-malarial can reduce the duration of gametocyte carriage and onward parasite transmission, localised hotspots represent a challenge to malaria control and eventual eradication. 相似文献
18.
Elisa Rossi Daniela Basso Carlo-Federico Zambon Filippo Navaglia Eliana Greco Michela Pelloso Serena Artuso Andrea Padoan Matilde Pescarin Ada Aita Dania Bozzato Stefania Moz Mara Cananzi Graziella Guariso Mario Plebani 《PloS one》2015,10(4)
Background
TNF-α and IFN-γ play a role in the development of mucosal damage in celiac disease (CD). Polymorphisms of TNFA and IFNG genes, as well as of the TNFRSF1A gene, encoding the TNF-α receptor 1, might underlie different inter-individual disease susceptibility over a common HLA risk background. The aims of this study were to ascertain whether five SNPs in the TNFA promoter (-1031T>C,-857C>T,-376G>A,-308G>A,-238G>A), sequence variants of the TNFRSF1A gene and IFNG +874A>T polymorphism are associated with CD in a HLA independent manner.Methods
511 children (244 CD, 267 controls) were genotyped for HLA, TNFA and INFG (Real Time PCR). TNFRSF1A variants were studied (DHPLC and sequence).Results
Only the rare TNFA-1031C (OR=0.65, 95% CI:0.44-0.95), -857T (OR=0.42, 95% CI:0.27-0.65), -376A (OR=2.25, 95% CI:1.12-4.51) and -308A (OR=4.76, 95% CI:3.12-7.26) alleles were significantly associated with CD. One TNFRSF1A variant was identified (c.625+10A>G, rs1800693), but not associated with CD. The CD-correlated TNFA SNPs resulted in six haplotypes. Two haplotypes were control-associated (CCGG and TTGG) and three were CD-associated (CCAG, TCGA and CCGA). The seventeen inferred haplotype combinations were grouped (A to E) based on their frequencies among CD. Binary logistic regression analysis documented a strong association between CD and HLA (OR for intermediate risk haplotypes=178; 95% CI:24-1317; OR for high risk haplotypes=2752; 95% CI:287-26387), but also an HLA-independent correlation between CD and TNFA haplotype combination groups. The CD risk for patients carrying an intermediate risk HLA haplotype could be sub-stratified by TNFA haplotype combinations.Conclusion
TNFA promoter haplotypes associate with CD independently from HLA. We suggest that their evaluation might enhance the accuracy in estimating the CD genetic risk. 相似文献19.
Erika Souza Vieira Tâmara Karoline de Oliveira Fontes Matheus Mendonça Pereira Hofsky Vieira Alexandre Daniel Pereira da Silva Cleide Mara Faria Soares Álvaro Silva Lima 《Bioprocess and biosystems engineering》2015,38(4):721-728
A novel strategy for the production of lipase by Bacillus sp. ITP-001 in a stirred tank fermenter using perfluorodecalin (PFD) was studied. Firstly, a response surface methodology 22 with three central points was employed to optimise the effect of agitation speed and aeration rate in lipase production. According to the response from the experimental designs, 300 rpm (revolutions per minute) and 0.5 vvm (air volume/liquid volume per minute) were found to provide the best condition (lipolytic activity: LA = 3,140.76 U mL?1). Then, the influence of PFD concentration on the fermentation process was evaluated. Incorporation of PFD at all concentrations above 1 % had no statistically significant influence on lipase production, that is, the previous optimisation allowed the reduction of the amount of PFD added besides increasing lipase production. Furthermore, PFD could be used in three sequential fermentations without altering the statistical production of lipase, reducing by 67 % the cost of PFD addition. 相似文献
20.
Caterina Longo Simonetta Piana Aimilios Lallas Elvira Moscarella Mara Lombardi Margherita Raucci Giovanni Pellacani Giuseppe Argenziano 《PloS one》2015,10(9)