Beneficial effect of voluntary exercise on experimental colitis in mice fed a high-fat diet : the role of irisin, adiponectin and proinflammatory biomarkers

Inflammatory bowel diseases (IBDs) are a heterogeneous group of disorders exhibited by two major phenotypic forms: Crohn‘s disease and ulcerative colitis. Although the aetiology of IBD is unknown, several factors coming from the adipose tissue and skeletal muscles, such as cytokines, adipokines and myokines, were suggested in the pathogenesis of ulcerative colitis; however, it has not been extensively studied whether voluntary exercise can ameliorate that disorder. We explored the effect of moderate exercise (i.e., voluntary wheel running) on the disease activity index (DAI), colonic blood flow (CBF), plasma irisin and adiponectin levels and real-time PCR expression of proinflammatory markers in mesenteric fat in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis fed a high-fat diet (HFD) compared to those on a standard chow diet (SD). Macroscopic and microscopic colitis in sedentary SD mice was accompanied by a significant fall in CBF, some increase in colonic tissue weight and a significant increase in the plasma levels of tumour necrosis factor-alpha (TNF-α), IL-6, monocyte chemotactic protein 1 (MCP-1) and IL-13 (p < 0.05). In sedentary HFD mice, colonic lesions were aggravated, colonic tissue weight increased and the plasma TNF-α, IL-6, MCP-1, IL-1β and leptin levels significantly increased. Simultaneously, a significant decrease in the plasma irisin and adiponectin levels was observed in comparison with SD mice (p < 0.05). Exercise significantly decreased macroscopic and microscopic colitis, substantially increased CBF and attenuated the plasma TNF-α, IL-6, MCP-1, IL-1β and leptin levels while raising the plasma irisin and the plasma and WAT concentrations of adiponectin in HFD mice (p < 0.05). We conclude that: (1) experimental colitis is exacerbated in HFD mice, possibly due to a fall in colonic microcirculation and an increase in the plasma and mesenteric fat content of proinflammatory biomarkers; and (2) voluntary physical activity can attenuate the severity of colonic damage in mice fed a HFD through the release of protective irisin and restoration of plasma adiponectin

Disruptive events in high-density cellular networks

Stochastic geometry models are used to study wireless networks, particularly cellular phone networks, but most of the research focuses on the typical user, often ignoring atypical events, which can be highly disruptive and of interest to network operators. We examine atypical events when a unexpected large proportion of users are disconnected or connected by proposing a hybrid approach based on ray launching simulation and point process theory. This work is motivated by recent results using large deviations theory applied to the signal-to-interference ratio. This theory provides a tool for the stochastic analysis of atypical but disruptive events, particularly when the density of transmitters is high. For a section of a European city, we introduce a new stochastic model of a single network cell that uses ray launching data generated with the open source RaLaNS package, giving deterministic path loss values. We collect statistics on the fraction of (dis)connected users in the uplink, and observe that the probability of an unexpected large proportion of disconnected users decreases exponentially when the transmitter density increases. This observation implies that denser networks become more stable in the sense that the probability of the fraction of (dis)connected users deviating from its mean, is exponentially small. We also empirically obtain and illustrate the density of users for network configurations in the disruptive event, which highlights the fact that such bottleneck behaviour not only stems from too many users at the cell boundary, but also from the near-far effect of many users in the immediate vicinity of the base station. We discuss the implications of these findings and outline possible future research directions.Comment: 8 pages, 11 figure

Support for a long lifetime and short end-to-end delays with TDMA protocols in sensor networks

This work addresses a tough challenge of achieving two opposing goals: ensuring long lifetimes and supporting short end-to-end delays in sensor networks. Obviously, sensor nodes must wake up often to support short delays in multi-hop networks. As event occurs seldom in common applications, most wake-up are useless: nodes waste energy due to idle listening. We introduce a set of solutions, referred to as LETED (limiting end-to-end delays), which shorten the wake-up periods, reduce idle listening, and save energy. We exploit hardware features of available transceivers that allow early detection of idle wake-up periods. This feature is introduced on top of our approach to reduce idle listening stemming from clock drift owing to the estimation of run-time drift. To evaluate LETED and other MAC protocols that support short end-to-end delays we present an analytical model, which considers almost 30 hardware and software parameters. Our evaluation revealed that LETED reduces idle listening by 15x and more against similar solutions. Also, LETED outperforms other protocols and provides significant longer lifetimes. For example, nodes with LETED work 8x longer than those with a common TDMA and 2x-3x longer than with protocols based on preamble sampling, like B-MAC

Carbon monoxide being hydrogen sulfide and nitric oxide molecular sibling, as endogenous and exogenous modulator of oxidative stress and antioxidative mechanisms in the digestive system

Oxidative stress reflects an imbalance between oxidants and antioxidants in favor of the oxidants capable of evoking tissue damage. Like hydrogen sulfide (H2S) and nitric oxide (NO), carbon monoxide (CO) is an endogenous gaseous mediator recently implicated in the physiology of the gastrointestinal (GI) tract. CO is produced in mammalian tissues as a byproduct of heme degradation catalyzed by the heme oxygenase (HO) enzymes. Among the three enzymatic isoforms, heme oxygenase-1 (HO-1) is induced under conditions of oxidative stress or tissue injury and plays a beneficial role in the mechanism of protection against inflammation, ischemia/reperfusion (I/R), and many other injuries. According to recently published data, increased endogenous CO production by inducible HO-1, its delivery by novel pharmacological CO-releasing agents, or even the direct inhalation of CO has been considered a promising alternative in future experimental and clinical therapies against various GI disorders. However, the exact mechanisms underlying behind these CO-mediated beneficial actions are not fully explained and experimental as well as clinical studies on the mechanism of CO-induced protection are awaited. For instance, in a variety of experimental models related to gastric mucosal damage, HO-1/CO pathway and CO-releasing agents seem to prevent gastric damage mainly by reduction of lipid peroxidation and/or increased level of enzymatic antioxidants, such as superoxide dismutase (SOD) or glutathione peroxidase (GPx). Many studies have also revealed that HO-1/CO can serve as a potential defensive pathway against oxidative stress observed in the liver and pancreas. Moreover, increased CO levels after treatment with CO donors have been reported to protect the gut against formation of acute GI lesions mainly by the regulation of reactive oxygen species (ROS) production and the antioxidative activity. In this review, we focused on the role of H2S and NO molecular sibling, CO/HO pathway, and therapeutic potential of CO-releasing pharmacological tools in the regulation of oxidative stress-induced damage within the GI tract with a special emphasis on the esophagus, stomach, and intestines and also two solid and important metabolic abdominal organs, the liver and pancreas

Investigating neighbourhood concentration of immigrants in Poland: explorative evidence from Kraków

Aim. This study contributes to research on new immigrant destinations in CEE by investigating the neighbourhood concentration of immigrants in Poland. We focus on Kraków – the second largest city – for which we have built a unique register-based dataset containing geocoded individual level data. To our knowledge, it is the first high-quality dataset of this type, prepared and used for research purposes in Poland. We use it to describe immigrants’ spatial allocation at a relatively early stage of immigration using the kNN approach. Results and conclusions. We find that whereas foreigners compose around 4.2% of city population, 50% of the city inhabitants live in the 200 kNNs with a share of foreigners below 2.2%. The DI for the immigrants is 0.45. Yet, a relatively high concentration could be seen among foreigners from Asia and America. However, immigrants from Ukraine and other Eastern European, non-EU countries are much more evenly spread around the city

Hydrogen Sulfide and Carbon Monoxide Protect Gastric Mucosa Compromised by Mild Stress Against Alendronate Injury

Background Alendronate is an inhibitor of osteoclast-mediated bone resorption, but its clinical utility is limited due to gastrointestinal complications including bleeding erosions. Aims We studied whether potent vasodilators hydrogen sulfide (H2S) and carbon monoxide (CO) can protect against alendronate-induced gastric lesions in rats exposed to mild stress. Methods Three series (A, B, and C) of Wistar rats received alendronate (150-700 mg/kg i.g., series A) with or without NaHS (5 mg/kg), H2S donor or CORM-2 (5 mg/kg) releasing CO administered i.g. 30 min before alendronate administration (series B) in rats exposed for 3 days before alendronate administration to mild stress (series C). The area of gastric lesions was assessed by planimetry, the gastric blood flow (GBF) was determined by H2-gas clearance technique, and H2S production via CSE/CBS/3- MST activity and the gastric expression of HO-1, HO-2, HIF-1a, NF-jB, iNOS, COX-2, IL-1b, TNF-a, GPx-1 and SOD-2 were analyzed by qPCR or Western blot. Results Alendronate dose-dependently produced gastric mucosal lesions and significantly decreased GBF, and these effects were exacerbated by mild stress. NaHS and CORM2 significantly reduced the alendronate-induced gastric lesions in non-stressed and stressed animals, but only NaHS but not CORM-2 raised H2S production. NaHS and CORM-2 inhibited gastric expression of HIF-1a protein and HO-1, HIF-1a, NF-jB, COX-2, iNOS, IL-1b, TNF-a mRNAs but failed to affect those of HO-2, GPx-1, and SOD-2. Conclusion Both H2S and CO released from their donors, NaHS and CORM-2, protect gastric mucosa compromised by stress against alendronate-induced gastric damage via mechanism involving downregulation of HIF-1a, NF-jB and proinflammatory factors COX-2, iNOS, IL-1b, and TNF-a

Disruptive events in high-density cellular networks

Stochastic geometry models are used to study wireless networks, particularly cellular phone networks, but most of the research focuses on the typical user, often ignoring atypical events, which can be highly disruptive and of interest to network operators. We examine atypical events when a unexpected large proportion of users are disconnected or connected by proposing a hybrid approach based on ray launching simulation and point process theory. This work is motivated by recent results [12] using large deviations theory applied to the signal-to-interference ratio. This theory provides a tool for the stochastic analysis of atypical but disruptive events, particularly when the density of transmitters is high. For a section of a European city, we introduce a new stochastic model of a single network cell that uses ray launching data generated with the open source RaLaNS package, giving deterministic path loss values. We collect statistics on the fraction of (dis)connected users in the uplink, and observe that the probability of an unexpected large proportion of disconnected users decreases exponentially when the transmitter density increases. This observation implies that denser networks become more stable in the sense that the probability of the fraction of (dis)connected users deviating from its mean, is exponentially small. We also empirically obtain and illustrate the density of users for network configurations in the disruptive event, which highlights the fact that such bottleneck behaviour not only stems from too many users at the cell boundary, but also from the near-far effect of many users in the immediate vicinity of the base station. We discuss the implications of these findings and outline possible future research directions

Exogenous asymmetric dimethylarginine (ADMA) in pathogenesis of ischemia-reperfusion-induced gastric lesions : interaction with protective nitric oxide (NO) and calcitonin gene-related peptide (CGRP)

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) synthesis inhibitor and pro-inflammatory factor. We investigated the role of ADMA in rat gastric mucosa compromised through 30 min of gastric ischemia (I) and 3 h of reperfusion (R). These I/R animals were pretreated with ADMA with or without the combination of l-arginine, calcitonin gene-related peptide (CGRP) or a small dose of capsaicin, all of which are known to afford protection against gastric lesions, or with a farnesoid X receptor (FXR) agonist, GW 4064, to increase the metabolism of ADMA. In the second series, ADMA was administered to capsaicin-denervated rats. The area of gastric damage was measured with planimetry, gastric blood flow (GBF) was determined by H2-gas clearance, and plasma ADMA and CGRP levels were determined using ELISA and RIA. ADMA significantly increased I/R-induced gastric injury while significantly decreasing GBF, the luminal NO content, and the plasma level of CGRP. This effect of ADMA was significantly attenuated by pretreatment with CGRP, l-arginine, capsaicin, or a PGE2 analogue. In GW4064 pretreated animals, the I/R injury was significantly reduced and this effect was abolished by co-treatment with ADMA. I/R damage potentiated by ADMA was exacerbated in capsaicin-denervated animals with a further reduction of CGRP. Plasma levels of IL-10 were significantly decreased while malonylodialdehyde (MDA) and plasma TNF-α contents were significantly increased by ADMA. In conclusion, ADMA aggravates I/R-induced gastric lesions due to a decrease of GBF, which is mediated by a fall in NO and CGRP release, and the enhancement of lipid peroxidation and its pro-inflammatory properties

Hydrogen sulphide production in healthy and ulcerated gastric mucosa of rats

Hydrogen sulphide (H2S) is produced endogenously via two enzymes dependent on pyridoxal phosphate (PLP): cystathionine beta-synthase (CBS, EC 4.2.1.22), cystathionase γ-liase (CTH, EC 4.4.1.1), and a third, 3-mercaptopyruvate sulfurtransferase (MPST, EC 2.8.1.2). H2S strengthens the defence mechanisms of the gastric mucosal barrier, and plays an important role in gastroprotection, including the increased resistance to damage caused by various irritants and non-steroidal anti-inflammatory drugs. The study was conducted to determine the role of H2S in ulcerated gastric mucosa of rats caused by immobilization in cold water (WRS). The activity and expression of γ-cystathionase, cystathionine β-synthase, 3-mercaptopyruvate sulfurtransferase, and rhodanese was compared with healthy mucosa, together with H2S generation, and cysteine, glutathione, and cystathionine levels. The results showed that the defence mechanism against stress is associated with stimulation of the production of H2S in the tissue and confirmed the observed advantageous effect of H2S on healing of gastric ulcers. In case of animals pretreated with exogenous sources of H2S and NaHS, and some changes observed in the ulcerated gastric mucosa tend to return to values found in the healthy tissue, a finding that is in accordance with the previously determined gastroprotective properties of H2S. The results presented in this paper point to the possible role of rhodanese in H2S production in the gastric mucosa of rats, together with the earlier mentioned three enzymes, which are all active in this tissue

The protective role of carbon monoxide (CO) produced by heme oxygenases and derived from the CO-releasing molecule CORM-2 in the pathogenesis of stress-induced gastric lesions : evidence for non-involvement of nitric oxide (NO)

Carbon monoxide (CO) produced by heme oxygenase (HO)-1 and HO-2 or released from the CO-donor, tricarbonyldichlororuthenium (II) dimer (CORM-2) causes vasodilation, with unknown efficacy against stress-induced gastric lesions. We studied whether pretreatment with CORM-2 (0.1–10 mg/kg oral gavage (i.g.)), RuCl3 (1 mg/kg i.g.), zinc protoporphyrin IX (ZnPP) (10 mg/kg intraperitoneally (i.p.)), hemin (1–10 mg/kg i.g.) and CORM-2 (1 mg/kg i.g.) combined with NG-nitro-l-arginine (l-NNA, 20 mg/kg i.p.), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 mg/kg i.p.), indomethacin (5 mg/kg i.p.), SC-560 (5 mg/kg i.g.), and celecoxib (10 mg/kg i.g.) affects gastric lesions following 3.5 h of water immersion and restraint stress (WRS). Gastric blood flow (GBF), the number of gastric lesions and gastric CO and nitric oxide (NO) contents, blood carboxyhemoglobin (COHb) level and the gastric expression of HO-1, HO-2, hypoxia inducible factor 1α (HIF-1α), tumor necrosis factor α (TNF-α), cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) were determined. CORM-2 (1 mg/kg i.g.) and hemin (10 mg/kg i.g.) significantly decreased WRS lesions while increasing GBF, however, RuCl3 was ineffective. The impact of CORM-2 was reversed by ZnPP, ODQ, indomethacin, SC-560 and celecoxib, but not by l-NNA. CORM-2 decreased NO and increased HO-1 expression and CO and COHb content, downregulated HIF-1α, as well as WRS-elevated COX-2 and iNOS mRNAs. Gastroprotection by CORM-2 and HO depends upon CO’s hyperemic and anti-inflammatory properties, but is independent of NO