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Nell'estate del 2004, 69 campioni di particolato atmosferico raccolti a Modena dall'Agenzia Regionale Prevenzione e Ambiente dell'Emilia-Romagna sono stati sottopostiad analisi elementale, per mezzo di fluorescenza a raggi X. Le concentrazioni riscontrate degli elementi sono successivamente state sottoposte ad analisi statistica multivariata, al fine dievidenziarne le correlazionie metterne in luce le sorgenti. Quattro sorgentisono state individuate, permettendo di quantificare la componente naturale (11 μg/m3) e quella antropica (20 μg/m3) del particolato nella cittàdurante il periodo diosservazione.

Background & Aims Acid hypersensitivity is claimed to be a symptomatic trigger in functional dyspepsia (FD); however, the neuroimmune pathway(s) and the mediators involved in this process have not been investigated systematically. Palmitoylethanolamide (PEA) is an endogenous compound, able to modulate nociception and inflammation, but its role in FD has not been assessed. Methods Duodenal biopsy specimens from FD and control subjects, and peroxisome proliferator-activated receptor-α (PPARα) null mice were cultured at a pH of 3.0 and 7.4. Mast cell (MC) number, the release of their mediators, and the expression of transient receptor potential vanilloid receptor (TRPV)1 and TRPV4, were evaluated. All measurements also were performed in the presence of a selective blocker of neuronal action potential (tetradotoxin). FD and control biopsy specimens in acidified medium also were incubated in the presence of different PEA concentrations, alone or combined with a selective PPARα or PPAR-γ antagonist. Results An acid-induced increase in MC density and the release of their mediators were observed in both dyspeptic patients and controls; however, this response was amplified significantly in FD. This effect was mediated by submucosal nerve fibers and up-regulation of TRPV1 and TRPV4 receptors because pretreatment with tetradotoxin significantly reduced MC infiltration. The acid-induced endogenous release of PEA was impaired in FD and its exogenous administration counteracts MC activation and TRPV up-regulation. Conclusions Duodenal acid exposure initiates a cascade of neuronal-mediated events culminating in MC activation and TRPV overexpression. These phenomena are consequences of an impaired release of endogenous PEA. PEA might be regarded as an attractive therapeutic strategy for the treatment of FD., Graphical abstract

Bleeding after bariatric surgery may occur during the operation or immediately after as a consequence of vascular or parenchymal injury related to laparoscopy or of failure after hemostasis at the suture line or anastomosis. Although the occurrence of bleeding is rare, it represents a true emergency and needs immediate diagnostic and therapeutic measures. Bleeding into the gastrointestinal tract causing hematemesis and/or melena is better assessed by endoscopy, whereas intraperitoneal bleeding is diagnosed by computed tomography. The first goal of treatment is to make the patient stable, whereas removal of the cause of bleeding is performed by endoscopic or radiological procedures after the diagnostic phase. When the patient remains unstable, treatment must be promptly established. Remedial surgery is the last resource of treatment. Delayed bleeding is related to peptic ulcer development and usually resolves with pharmacological and endoscopic treatment.

Background: Polymorphisms of genes involved in the regulation of the immune response are risk factors for achalasia, but their contribution to disease pathogenesis is unknown. Nitric oxide is involved in both immune function and inhibitory neurotransmission. Objective: to assess the association and the functional relevance of the CCTTT inducible Nitric Oxide Synthase (NOS2) gene promoter polymorphism in achalasia. Methods: Genomic DNA was isolated from 181 achalasia patients and 220 controls. Genotyping of the (CCTTT)n repeats was performed by PCR and capillary electrophoresis, and data analyzed by considering the frequency of the different alleles. HT29 cells were transfected with iNOS luciferase promoter-reporter plasmids containing different (CCTTT)n. Results: The alleles’ distribution ranged from 7 to 18, with a peak frequency at 12 repeats. Analysis of the allele frequencies revealed that individuals carrying 10 and 13 CCTTT repeats were respectively less and more frequent in achalasia (OR 0.5, 95% CI 0.3-0.5 and OR 1.6, 95% CI 1-2.4, all p

Sitagliptin and saxagliptin are oral hypoglycemic agents inhibitors of DPP-4, indicated in the treatment of type 2 diabetes mellitus in combination with metformin, in patients who have not achieved adequate glycemic control. In our study we enrolled 128 decompensated type 2 diabetes patients while on metformin maximum dosage. At time 0’ we have detected, body mass index (BMI), total cholesterol, high- and low-density lipoproteins (HDL and LDL), triglycerides, transaminases and pancreatic amylase; patients were randomized to receive sitagliptin or saxagliptin; follow-up was performed after 4 months with the revaluation of the same variables and adverse events. In both sitagliptin and saxagliptin groups we observed a significant reduction in fasting glucose, glycated hemoglobin, weighing, BMI, triglycerides, while the reduction in total cholesterol, LDL cholesterol did not reach statistical significance. There was no suspension of therapy, adverse events appeared minor and temporary. In conclusion, our observations highlight the almost identical efficacy of sitagliptin and saxagliptin. These data reinforce even more the idea that we should think about this class of drugs as the next step in patients failing therapy with metformin.

The endocannabinoid system (ECS) is an endogenous signalling pathway involved in the control of several gastrointestinal (GI) functions at both peripheral and central levels. In recent years, it has become apparent that the ECS is pivotal in the regulation of GI motility, secretion and sensitivity, but endocannabinoids (ECs) are also involved in the regulation of intestinal inflammation and mucosal barrier permeability, suggesting their role in the pathophysiology of both functional and organic GI disorders. Genetic studies in patients with irritable bowel syndrome (IBS) or inflammatory bowel disease have indeed shown significant associations with polymorphisms or mutation in genes encoding for cannabinoid receptor or enzyme responsible for their catabolism, respectively. Furthermore, ongoing clinical trials are testing EC agonists/antagonists in the achievement of symptomatic relief from a number of GI symptoms. Despite this evidence, there is a lack of supportive RCTs and relevant data in human beings, and hence, the possible therapeutic application of these compounds is raising ethical, political and economic concerns. More recently, the identification of several EC‐like compounds able to modulate ECS function without the typical central side effects of cannabino‐mimetics has paved the way for emerging peripherally acting drugs. This review summarizes the possible mechanisms linking the ECS to GI disorders and describes the most recent advances in the manipulation of the ECS in the treatment of GI diseases.

Background Diarrhea is a severe complication in HIV-1-infected patients with Trans-activator of transcription (HIV-1 Tat) protein being recognized as a major underlying cause. Beside its direct enterotoxic effects, Tat protein has been recently shown to affect enteric glial cell (EGC) activity. EGCs regulate intestinal inflammatory responses by secreting pro-inflammatory molecules; nonetheless, they might also release immune-regulatory factors, as palmytoilethanolamide (PEA), which exerts anti-inflammatory effects by activating PPARα receptors. We aimed at clarifying whether EGCs are involved in HIV-1 Tat-induced diarrhea and if PEA exerts antidiarrheal activity. Methods Diarrhea was induced by intracolonic administration of HIV-1 Tat protein in rats at day 1. PEA alone or in the presence of peroxisome proliferator-activated receptor (PPAR) antagonists was given intraperitoneally from day 2 to day 7. S100B, iNOS, NF-kappaB, TLR4 and GFAP expression were evaluated in submucosal plexi, while S100B and NO levels were measured in EGC submucosal plexi lysates, respectively. To verify whether PEA effects were PPARα-mediated, PPARα−/− mice were also used. After 7 days from diarrhea induction, endogenous PEA levels were measured in submucosal plexi homogenates deriving from rats and PPARα−/− mice. Results HIV-1 Tat protein induced rapid onset diarrhea alongside with a significant activation of EGCs. Tat administration significantly increased all hallmarks of neuroinflammation by triggering TLR4 and NF-kappaB activation and S100B and iNOS expression. Endogenous PEA levels were increased following HIV-1 Tat exposure in both wildtype and knockout animals. In PPARα−/− mice, PEA displayed no effects. In wildtype rats, PEA, via PPARα-dependent mechanism, resulted in a significant antidiarrheal activity in parallel with marked reduction of EGC-sustained neuroinflammation. Conclusions EGCs mediate HIV-1 Tat-induced diarrhea by sustaining the intestinal neuroinflammatory response. These effects are regulated by PEA through a selective PPARα-dependent mechanism. PEA might be considered as an adjuvant therapy in HIV-1-induced diarrhea. Electronic supplementary material The online version of this article (10.1186/s12974-018-1126-4) contains supplementary material, which is available to authorized users.