The enteric nervous system : new developments and emerging concepts

The enteric nervous system (ENS) is an integrative neuronal network, organized in two ganglionated plexuses, myenteric and submucosal, composed of neurons and enteric glial cells, controlling the activity of the smooth muscle of the gut, mucosal secretion and blood flow. The ENS contains as many neurons as the spinal cord, and the functional and chemical diversity of enteric neurons closely resembles that of the central nervous system. This highly integrated neural system is also referred to as the ‘brain-in-the-gut’, because of its capability to function in the absence of nerve inputs from the central nervous system.peer-reviewe

The enteric nervous system : new developments and emerging concepts

The enteric nervous system (ENS) is an integrative neuronal network, organized in two ganglionated plexuses, myenteric and submucosal, composed of neurons and enteric glial cells, controlling the activity of the smooth muscle of the gut, mucosal secretion and blood flow. The ENS contains as many neurons as the spinal cord, and the functional and chemical diversity of enteric neurons closely resembles that of the central nervous system. This highly integrated neural system is also referred to as the ‘brain-in-the-gut’, because of its capability to function in the absence of nerve inputs from the central nervous system.peer-reviewe

Sustainable Synthesis of Epoxidized Cynara C. Seed Oil

The use of non-edible vegetable oils to produce oleochemicals has been attracting more attention in recent years. Cardoon seed oil, derived from the Cynara C. plant, growing in marginal and contaminated lands, represents a non-edible alternative to soybean oil to obtain plasticizers through epoxidation reaction. The use of hydrogen peroxide as oxidant and in the presence of a heterogeneous catalyst allows overcoming the limits of epoxidation with peracids. γ-alumina has been shown to have an active catalyst epoxidation reaction with hydrogen peroxide, mainly using acetonitrile as solvent. However, the use of acetonitrile as solvent is widely debated due to its hazardous character and health issues. For these reasons, the influence of solvent on the reaction was studied in this work to find a more environmentally friendly and stable solvent. The study showed that the epoxidation reaction takes place also in the absence of solvent although with lower selectivity. The type of solvent influences both the epoxidation and decomposition reactions of hydrogen peroxide. γ-valerolactone was found to be the most promising solvent for cardoon oil epoxidation reaction. This finding represents a noteworthy novelty in the field of epoxidation of vegetable oils with hydrogen peroxide, opening the way to greener and cleaner process. Finally, an optimization study showed that the most effective molar ratio between hydrogen peroxide and double bonds for better selectivity was 4.5 and the need to use the highest possible initial concentration of hydrogen peroxide (approximately 60 wt. %)

Gastric emptying, small intestinal transit and fecal output in dystrophic (mdx) mice

Duchenne muscular dystrophy (DMD), which results from deficiency in dystrophin, a sarcolemma protein of skeletal, cardiac and smooth muscle, is characterized by progressive striated muscle degeneration, but various gastrointestinal clinical manifestations have been observed. The aim was to evaluate the possible impact of the dystrophin loss on the gastrointestinal propulsion in mdx mice (animal model for DMD). The gastric emptying of a carboxymethyl cellulose/phenol red dye non-nutrient meal was not significantly different at 20 min from gavaging between wild-type and mdx mice. The intestinal transit and the fecal output were significantly decreased in mdx versus normal animals, although the length of the intestine was similar in both animals. The present results provide evidence for motor intestinal alterations in mdx mice in in vivo conditions

Angiotensin II contractile effects in mouse colon: role for pre- and post-junctional AT1A receptors

Aim: This study investigates whether a local renin–angiotensin system (RAS) exists in mouse colon and whether angiotensin II (Ang II) may play a role in the regulation of the contractile activity. Methods: Isometric recordings were performed in vitro on the longitudinal muscle of mouse proximal and distal colon. Transcripts encoding for RAS components were investigated by RT-PCR. Results: Ang II caused, in both preparations, a concentration-dependent contractile effect, antagonized by losartan, AT1 receptor antagonist, but not by PD123319, AT2 receptor antagonist. The combination of losartan plus PD123319 caused no change on the Ang II-induced contraction than losartan alone. Tetrodotoxin, neural blocker, reduced the contractile response to Ang II in the proximal colon, whilst the response was abolished in the distal colon. In both preparations, atropine, muscarinic receptor antagonist, or SR140333, NK1 receptor antagonist, reduced the Ang II responses. Ondansetron, 5-HT3 receptor antagonist, SR48968, NK2 receptor antagonist, or hexamethonium, nicotinic receptor antagonist, were ineffective. The joint application of atropine and SR140333 produced no additive effect. Atropine reduced NK1-induced contraction. Transcripts encoding RAS components were detected in the colon samples. However, just AT1A mRNA was expressed in both preparations, and AT2 mRNA was expressed only in the distal colon. Conclusion: In the murine colon, local RAS may play a significant role in the control of contractile activity. Ang II positively modulates the spontaneous contractile activity via activation of post-junctional and pre-junctional AT1A receptors, the latter located on the enteric neurones, modulating the release of tachykinins and acetylcholine

Angiotensin II positively modulates the spontaneous contractile activity of mouse and human colon via activation of AT1 receptors.

Objective: Angiotensin II (Ang II) is a potent smooth muscle contractile neurohumoral agonist but has not been much investigated with regard to gastrointestinal motor activity. Ang II effects are mediated by specific receptors, the Ang II type 1 (AT1) and the Ang II type 2 (AT2) receptors, which are well expressed in the gut. In this study we evaluated the effects of Ang II on the contractile activity of longitudinal muscle from mouse and human colon and we analysed the subtype(s) of receptors involved in the observed effects. Methods: Mechanical responses to Ang II, in the absence or in the presence of different drugs, were assessed in vitro in colonic longitudinal muscle from mice and humans, as changes in isometric tension. Results: In the murine proximal and distal colon Ang II induced a concentration-dependent muscular contraction, which was reduced by the AT1 receptor antagonist, losartan, but it was not affected by the AT2 receptor antagonist, PD123319. Pretreatment with TTX, sodium voltage-gated neural channel blocker, partially reduced the contractile response to Ang II in the proximal colon, while abolished it in the distal colon. Atropine, muscarinic receptor antagonist, or SR140333, NK1 receptor antagonist, reduced the TTX-sensitive excitatory effects induced by Ang II in both preparations. On the contrary, hexamethonium, nicotinic receptor antagonists, ondansetron, 5-HT3 receptor antagonist, or SR48968, NK2 receptor antagonist, were ineffective. The contraction induced by a selective NK1 receptor agonist was reduced by atropine, whilst SR140333 did not affected carbachol inducing muscular contraction. Ang II induced a muscular contraction even in the human distal colonic longitudinal muscle preparations. The concentration–response curve was shifted to the right by losartan but it was unaffected by PD123319. TTX and atropine partially antagonized the response to Ang II. Conclusion: In the longitudinal muscle preparations from mouse and human colon Ang II positively modulates the spontaneous contractile activity via activation of post-junctional and pre-junctional AT1 receptors, the latter located on the enteric nerves and modulating the release of tachykinins and acethylcoline. In mouse tachykinergic neurons and cholinergic neurons are sequentially recruited by Ang II to induce muscular contraction

In vivo and Post-synthesis Strategies to Enhance the Properties of PHB-Based Materials: A Review

The transition toward “green” alternatives to petroleum-based plastics is driven by the need for “drop-in” replacement materials able to combine characteristics of existing plastics with biodegradability and renewability features. Promising alternatives are the polyhydroxyalkanoates (PHAs), microbial biodegradable polyesters produced by a wide range of microorganisms as carbon, energy, and redox storage material, displaying properties very close to fossil-fuel-derived polyolefins. Among PHAs, polyhydroxybutyrate (PHB) is by far the most well-studied polymer. PHB is a thermoplastic polyester, with very narrow processability window, due to very low resistance to thermal degradation. Since the melting temperature of PHB is around 170–180°C, the processing temperature should be at least 180–190°C. The thermal degradation of PHB at these temperatures proceeds very quickly, causing a rapid decrease in its molecular weight. Moreover, due to its high crystallinity, PHB is stiff and brittle resulting in very poor mechanical properties with low extension at break, which limits its range of application. A further limit to the effective exploitation of these polymers is related to their production costs, which is mostly affected by the costs of the starting feedstocks. Since the first identification of PHB, researchers have faced these issues, and several strategies to improve the processability and reduce brittleness of this polymer have been developed. These approaches range from the in vivo synthesis of PHA copolymers, to the enhancement of post-synthesis PHB-based material performances, thus the addition of additives and plasticizers, acting on the crystallization process as well as on polymer glass transition temperature. In addition, reactive polymer blending with other bio-based polymers represents a versatile approach to modulate polymer properties while preserving its biodegradability. This review examines the state of the art of PHA processing, shedding light on the green and cost-effective tailored strategies aimed at modulating and optimizing polymer performances. Pioneering examples in this field will be examined, and prospects and challenges for their exploitation will be presented. Furthermore, since the establishment of a PHA-based industry passes through the designing of cost-competitive production processes, this review will inspect reported examples assessing this economic aspect, examining the most recent progresses toward process sustainability

Aging modifies receptor expression but not muscular contractile response to angiotensin II in rat jejunum

: The involvement of renin-angiotensin system in the modulation of gut motility and age-related changes in mRNA expression of angiotensin (Ang II) receptors (ATR) are well accepted. We aimed to characterize, in vitro, the contractile responses induced by Ang II, in jejunum from young (3-6 weeks old) and old rats (≥ 1 year old), to evaluate possible functional differences associated to changes in receptor expression. Mechanical responses to Ang II were examined in vitro as changes in isometric tension. ATR expression was assessed by qRT-PCR. Ang II induced a contractile effect, antagonized by losartan, AT1R antagonist, and increased by PD123319, AT2R antagonist, as well by neural blocker ω-conotoxin and by nitric oxide (NO) synthase inhibitor. No difference in the response was observed between young and old groups. AT1 receptor-mediated contractile response was decreased by U-73122, phospholipase C (PLC) inhibitor; or 2-aminoethoxy-diphenylborate (2-APB), inositol triphosphate (IP3) receptor inhibitor; or nifedipine, L-type calcium channel blocker. Age-related changes in the expression of both AT1 receptor subtypes, AT1a and AT1b, and of AT2 receptors were detected. In conclusion, Ang II modulates the spontaneous contractility of rat jejunum via postjunctional AT1 receptors, involving Ca2+ mobilization from intracellular stores, via PLC/IP3 pathway, and Ca2+ influx from extracellular space, via L-type channels. Prejunctional AT2 receptors would counteract AT1 receptor effects, via NO synthesis. The observed age-related differences in the expression of all AT receptor subtypes are not reflected in the muscular contractile response to Ang II

Arginine vasopressin, via activation of post-junctional V1 receptors, induces contractile effects in mouse distal colon

The aim of this study was to analyze whether arginine vasopressin (AVP) may be considered a modulator of intestinal motility. In this view, we evaluated, in vitro, the effects induced by exogenous administration of AVP on the contractility of mouse distal colon, the subtype(s) of receptor(s) activated and the action mechanism. Isometric recordings were performed on longitudinal and circular muscle strips of mouse distal colon. AVP (0.001 nM–100 nM) caused concentration-dependent contractile effects only on the longitudinal muscle, antagonized by the V1 receptor antagonist, V-1880. AVP-induced effect was not modified by tetrodotoxin, atropine and indomethacin. Contractile response to AVP was reduced in Ca2+-free solution or in the presence of nifedipine, and it was abolished by depletion of calcium intracellular stores after repetitive addition of carbachol in calcium-freemediumwith addition of cyclopiazonic acid.U-73122, an inhibitor of the phospholipase C, effectively antagonized AVP effects, whilst it was not affected by an adenylyl cyclase inhibitor. Oxytocin induced an excitatory effect in the longitudinalmuscle of distal colon at very high concentrations, effect antagonized by V-1880. The results of this study shown that AVP, via activation of V1 receptors, is able to modulate positively contractile activity of longitudinal muscle of mouse distal colon, independently by enteric nerve activation and prostaglandin synthesis. Contractile response is achieved by increase in cytoplasmatic Ca2+ concentration via extracellular Ca2+ influx from L-type Ca2+ channels and via Ca2+ release from intracellular stores through phospholipase C pathway. No modulation has been observed on the contractility of the circular muscle

Understanding Marine Biodegradation of Bio-Based Oligoesters and Plasticizers

The study reports the enzymatic synthesis of bio-based oligoesters and chemo-enzymatic processes for obtaining epoxidized bioplasticizers and biolubricants starting from cardoon seed oil. All of the molecules had MW below 1000 g mol-1 and were analyzed in terms of marine biodegradation. The data shed light on the effects of the chemical structure, chemical bond lability, thermal behavior, and water solubility on biodegradation. Moreover, the analysis of the biodegradation of the building blocks that constituted the different bio-based products allowed us to distinguish between different chemical and physicochemical factors. These hints are of major importance for the rational eco-design of new benign bio-based products. Overall, the high lability of ester bonds was confirmed, along with the negligible effect of the presence of epoxy rings on triglyceride structures. The biodegradation data clearly indicated that the monomers/building blocks undergo a much slower process of abiotic or biotic transformations, potentially leading to accumulation. Therefore, the simple analysis of the erosion, hydrolysis, or visual/chemical disappearance of the chemical products or plastic is not sufficient, but ecotoxicity studies on the effects of such small molecules are of major importance. The use of natural feedstocks, such as vegetable seed oils and their derivatives, allows the minimization of these risks, because microorganisms have evolved enzymes and metabolic pathways for processing such natural molecules