Objective. The role of adipokines such as resistin, leptin, and adiponectin could be pivotal in the molecular crosstalk between the inflamed intestine and the surrounding mesenteric adipose tissue. Our aims were to a) evaluate their circulating concentrations in patients with active celiac disease (ACD) and compare them to those in patients with diarrhea-predominant irritable bowel syndrome (IBS-d) and healthy subjects; b) establish the impact of genetic variability in resistin; and c) evaluate whether a 1-year gluten-free diet (GFD)modifies circulating concentrations of resistin, leptin, and adiponectin in celiac patients. Material and methods. The study included 34 ACD patients, 29 IBS-d patients, and 27 healthy controls. Circulating concentrations of resistin, leptin, adiponectin, IL-6, and IL-8 were evaluated at the time of enrollment. Resistin +299 G/A polymorphism was also analysed. In CDpatients, biochemical measurements were repeated after a 1-year GFD. Results. Along with higher IL-6 and IL-8 plasma levels, higher resistin and adiponectin concentrations were found in ACD and IBS-d patients compared with controls (p: 0.0351 and p: 0.0020, respectively). Resistin values proved to be predictable from a linear combination of IL-8 and +299 polymorphism. GFD affected resistin (p: 0.0009), but not leptin and adiponectin concentrations. Conclusions. Our data suggest that these adipokines are involved inmodulating inflammatory processes in both CD and IBS-d patients. Alterations in the adipokine profile as well as the higher prevalence of the resistin +299 G/A SNP A allele compared to controls support the hypothesis that, at least in well-defined cases of IBS, a genetic component may also be supposed.

Objective To examine the role of lipoprotein(a) [Lp(a)] on the inflammatory response of cells in the nervous system by investigating its effect on lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) secretion. Materials and methods Human astrocytoma U373 cells were treated with recombinant apolipoprotein(a) [r-apo(a)] A10K (175–11 nM), alone or in combination with LPS (100 and 10 ng/ml). IL-6 levels were evaluated by immunoblotting. Statistical analysis was performed by one-way ANOVA. Results r-apo(a) caused dose-dependent inhibition of LPS-induced IL-6 secretion (100 ng/ml LPS, p = 0.0205; 10 ng/ml LPS, p = 0.0005). Pre-treatment of cells with 88 nM r-apo(a), rinsing, and activation with 10 ng/ml LPS did not reverse the inhibition (p = 0.0048), which could be reversed by supplementation with excess serum (5–20%) (p = 0.0454) or recombinant CD14 (2.0–0.05 lg/ml) (p = 0.0230). Conclusions Our data indicate that apo(a) plays a natural anti-endotoxin role which relies on its interference with cell-associated and serum components of LPS signaling.

The goal of this study is the chemical-physical characterization of a drug delivery system for Photodynamic Therapy (PDT) [1]: Chlorophyll a (Chl a) entrapped in a water-soluble matrix made of Ca2+ cross-linked alginic acid [2]. Chl a, a lipophilic natural pigments, is a molecule with characteristic photosensitising properties usable in PDT. In PDT the photosensitizer, selectively accumulated in malignant tissues, produces, upon light irradiation, reactive oxygen species (ROS) which are responsible for cytotoxicity of neoplastic cells and tumor regression since induce cellular damage via apoptosis, necrosis, or both. The Chl a/alginate microspheres produced were characterized by means of different techniques as UV-Vis absorption and emission spectroscopy, FT-IR spectroscopy, Atomic Force Microscopy, Dynamic Light Scattering and Differential Scanning Calorimetry. Moreover, it was estimated the ROS production, mainly singlet oxygen (1O2) by means of a selective luminescent probe, Singlet Oxygen Sensor Green [3] and in vitro tests were carried out on human adenocarcinoma cells (HT29). [1] R.M. Szeimies, S. Karrer, S. Radakovic-Fijan. J. Am. Acad. Dermatol., 2002, 47, 259-262. [2] G.T. Grant, E.R. Morris, D.A. Rees, P.J.C. Smith, D. Thom. FEBS letters, 1973, 32,195-198. [3] A. Gollmer, J. Arnbjerg, H. Frances, F.H. Blaikie, B.Wett Pedersen, T. Breitenbach, K. Daasbjerg, P.R. Ogilby. Photochemistry and Photobiology, 2011, 87, 671–679.

Our group has previously shown that the administration of pasta enriched along with the prebiotic inulin induces a significant reduction in triglyceride and glucose levels with a significant delay in gastric emptying (GE) rates. This protective effect may occur by affecting the release of a number of gut peptides involved in the control of gastrointestinal motility. The aim of the present study was to evaluate the effects of inulin-enriched pasta on the circulating levels of neurotensin (NT), somatostatin (SS), and corticotropin-releasing factor (CRF) in relation to the GE time in young healthy subjects. Methods Twenty healthy young male volunteers completed a randomized double-blind crossover study consisting of a 2-week run-in period and two 5-week study periods (11% inulin-enriched/control pasta), with an 8-week wash-out period in between. Gut peptide concentrations were evaluated by radioimmunoassay. GE time was evaluated by ultrasonography. Results The prebiotic treatment significantly increased the area under the curve (AUC) values of both NT and SS (p\0.05 Dunn’s post-test). With regard to gastric motility, along with a significant delay in both the final time and T1/2 gastric emptying time, a positive correlation was found between T1/2 and SS AUC values (r = 0.57, p = 0.009) in the inulin-enriched pasta group. Conclusion These results support the hypothesis that inulin plays an active role in mechanisms affecting the release of these gut peptides, which may modulate the gastric emptying of digesta.

Apart from the intestinal environment, inulin induces physiological effects, which includes a reduction in glucose and lipid concentrations and modulation of gastrointestinal motility through the release of different peptides. We hypothesized that inulin-enriched pasta may also improve small intestine permeability in relation to zonulin and glucagon-like peptide 2(GLP-2) levels in healthy young subjects. Twenty healthy, young male volunteers completed a randomized, double-blind crossover study consisting of a 2-week run-in period and two 5-week study periods (11% inulin-enriched or control pasta), with an 8-week washout period in between. The intestinal barrier function was assessed by lactulose-mannitol excretion in urine. Zonulin values and GLP-2 release were evaluated by enzyme-linked immunosorbent assay. In the inulin group, the urinary lactulose recovery was significantly lower than the other 2 groups. There were no significant differences in urinary mannitol levels between groups. Accordingly, the lactulose-mannitol excretion ratio was significantly decreased in the inulin-enriched pasta group compared with the other 2 groups. The inulin-enriched pasta group had significantly lower zonulin serum values and significantly higher GLP-2 basal values when compared with the baseline and control pasta groups. The dietary use of inulin-enriched pasta preserves intestinal mucosal barrier functioning and modulates circulating levels of zonulin and GLP-2, suggesting that prebiotics could be used in the prevention of gastrointestinal diseases and metabolic disorders.

The barrier between blood and CSF contributes to homeostasis of the CNS and protects it from potentially harmful substances present in the blood. Lipoproteins present in the CSF are clearly distinct from their plasma counterparts. Human CSF lipoproteins contain mainly Apo AI and Apo E, the former deriving mostly from plasma after crossing the blood–cerebrospinal fluid barrier, the latter being also produced by CNS. Apo AI and E containing lipoproteins in the brain are key players in transport and delivery of lipids, cholesterol homeostasis, and are also involved in CNS remodeling mechanisms. On the other hand, the isoform apo E4 represents the most important genetic risk factor for sporadic and familial late-onset Alzheimer’s disease and is involved in brain injury and neurodegenerative diseases. Apo B containing lipoproteins are not produced by CNS and the characterization of normal human CSF lipoproteins did not allowed the isolation of low density lipoproteins. which is characterized by a dimensional polymorphism. Lipoprotein(a) is a well known risk factor for athero-thrombosis. The pathological role of Lipoprotein(a) is strictly associated with its plasma concentrations and the size of apo(a) isoforms, with inverse relation. The pathophysiology of Lipoprotein(a) in cardio and cerebrovascular system is widely studied. Recently, we demonstrated that, in neuroinflammatory and neurodegenerative disorders, Lipoprotein(a) can cross a dysfunctional blood-CSF barrier and be found in the CSF. This chapter focuses on the physiological presence of the lipoproteins in CNS, on the pathological aspects deriving from their isoforms, and in particular on the anomalous presence in CSF of Lipoprotein(a)

Abstract: Different lines of evidence suggest that higher intake of fiber may somehow protect against metabolic syndrome. The prebiotic inulin has widely been studied in relation to its putative beneficial effects on lipid and glucose metabolism. Therefore, adding inulin to diet may be a suitable strategy to prevent metabolic syndrome. Aim of the present study was to evaluate the effects of the daily consumption of inulin-enriched pasta on lipid and glucose metabolism as well as on gastrointestinal motility in young healthy subjects. Methods. Twenty-two healthy young male volunteers entered a randomized double blind cross-over study consisting of a 2-weeks a runin period, two 5-weeks study periods (11% inulin-enriched or control pasta), and an 8-weeks wash-out period in between. Serum lipid and glucose concentrations were evaluated by routine biochemical analyses. Gastric emptying time and electrical activity were noninvasively evaluated by ultrasound and electrogastrography. Data were analyzed by Friedman Repeated Measures ANOVA test. Results. Significant differences among baseline and the treatment group were found for HDL-cholesterol (p=0.004), total cholesterol/HDLcholesterol ratio (p=0.006), triglycerides (p=0.04), fasting glucose level (p=0.044), fructosamine (p=0.0478), HbA1c (p=0.04), and homeostatic model assessment (HOMA-IR) (p=0.045). The gastric emptying, expressed as final emptying time, was found significantly delayed in the group that assumed inulin-enriched pasta (p=0.008). Conclusions. Inulin-enriched pasta improved lipidic and glicidic metabolism as well as the insulin resistance in healthy young subjects. In addition, it delayed the gastric emptying time which may represent the physiological counterpart of its metabolic effects.

Lipoprotein(a) is an LDL-like lipoparticle having the distinctive multi-kringle apolipoprotein(a). Although the physiological roles of lipoprotein(a) have been somewhat elusive, its pathological effects, closely related to plasma concentrations, have been widely studied. Several variants of the LPA gene contribute to its differential expression, and to lipoprotein(a) levels and pathogenicity. Although most of the variations in lipoprotein(a) concentrations are under genetic control, a relationship between plasma levels, apolipoprotein(a) phenotypes, anthropometric and biochemical factors, and environmental-associated events has been reported in many studies. Study of transgenic animals, which bypasses the absence of lipoprotein(a) in common laboratory animals, is an excellent model to examine the function of increased plasma lipoprotein(a) in differing pathological conditions or in cases of dietary intervention. This chapter offers an overview of some of the non-genetic factors which have modest, albeit significant, effects on lipoprotein(a) levels, also assessing their possible interactions with specific apolipoprotein(a) genotypes. The effects of estrogenreplacement therapy and dietary interventions in the modulation of lipoprotein(a) levels, and the influence of age are evaluated, taking into account their implications in the atherogenic risk. Lastly, the controversial role of lipoprotein(a) as an acute phase reactant and, in particular, its possible beneficial role in surgical trauma are discussed.

Objectives: To investigate peripheral brain-derived neurotrophic factor (BDNF) concentrations in the perioperative period, their relationship with transforming growth factor-β1 (TGF-β1 tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-6 genetics. Design and methods: Prospective, observational study. BDNF, TGF-β1, IL-6 and TNF-α were analysed at baseline (T0), 5 h (T1), 24 h (T2) and 5 days (T3) after surgery, in 21 patients. The IL-6 −174 G/C polymorphism was genotyped. Results: Serum BDNF concentrations decreased (P=0.048), correlated with TGF-β1 (r=0.610 at T1, r=0.493 at T2, r=0.554 at T3). Plasma BDNF concentrations raised (P=0.049), correlated with IL-6 and TNF-α at T1 (r=0.495 and r=0.441, respectively). BDNF response was predictable from TNF-α and IL-6 concentrations and the IL-6 −174 G/C genotype. Conclusion: Serum and plasma BDNF concentrations could relate to platelet activation and inflammatory response, respectively. IL-6 genetics played a role in the BDNF acute response.

Abstract Background: Plasminogen activation is a ubiquitous source of fibrinolytic and proteolytic activity. Besides its role in prevention of thrombosis, plasminogen is involved in inflammatory reactions in the central nervous system. Plasminogen has been detected in the cerebrospinal fluid (CSF) of patients with inflammatory diseases; however, its origin remains controversial, as the blood–CSF barrier may restrict its diffusion from blood. Methods: We investigated the origin of plasminogen in CSF using Alexa Fluor 488–labelled rat plasminogen injected into rats with systemic inflammation and blood–CSF barrier dysfunction provoked by lipopolysaccharide (LPS). Near-infrared fluorescence imaging and immunohistochemistry fluorescence microscopy were used to identify plasminogen in brain structures, its concentration and functionality were determined by Western blotting and a chromogenic substrate assay, respectively. In parallel, plasminogen was investigated in CSF from patients with Guillain-Barré syndrome (n = 15), multiple sclerosis (n = 19) and noninflammatory neurological diseases (n = 8). Results: Endogenous rat plasminogen was detected in higher amounts in the CSF and urine of LPS-treated animals as compared to controls. In LPS-primed rats, circulating Alexa Fluor 488–labelled rat plasminogen was abundantly localized in the choroid plexus, CSF and urine. Plasminogen in human CSF was higher in Guillain-Barré syndrome (median = 1.28 ng/μl (interquartile range (IQR) = 0.66 to 1.59)) as compared to multiple sclerosis (median = 0.3 ng/μl (IQR = 0.16 to 0.61)) and to noninflammatory neurological diseases (median = 0.27 ng/μl (IQR = 0.18 to 0.35)). Conclusions: Our findings demonstrate that plasminogen is transported from circulating blood into the CSF of rats via the choroid plexus during inflammation. Our data suggest that a similar mechanism may explain the high CSF concentrations of plasminogen detected in patients with inflammation-derived CSF barrier impairment.