Transforming growth factor-a (TGF-a) plays an important role in both proliferation and differentiation of mucosal cells at the gastrointestinal level, including stomach, where it is constitutively ...produced. This study evaluated the immunohistochemical distribution of TGF-a within whole gastric mucosa in rats, through the examination of seriate sections. Each stomach was opened along the greater curvature, pinned upon a cork plate, fixed in formalin and cut in 2-mm parallel strips which were sequentially superimposed on a glass slide. Sections were immunostained for TGF-a and pictures were taken from three areas: greater and lesser curvature; mucosa lying between the two curvatures. The sections were graded on the basis of the intensity of TGF-a staining, which was scored as follows: 0) no staining; 1) weakly positive; 2) intensely positive. The percent number of immunopositive cells and a mean intensity were calculated. Gastric mucosa showed a marked immunopositivity to TGF-a, mainly in parietal cells whose cytoplasm displayed moderate to intense staining. Positive cells (and the mean intensity) of total mucosa were 15.7±6.1% (1.13±0.42). However, they were not uniformly distributed, being 26.3±1.9% (1.67±0.24) in the mucosa lying between the two curvatures, 12.4±2.5% (1.52±0.22) along the lesser curvature and 8.3±2.1% (0.31±0.17) along the greater curvature. These results show that parietal cells of rat gastric mucosa exhibit immunoreactivity to TGF-a. Considering the gastroprotective effects of this factor, its non-homogeneous distribution within different areas may be of importance in understanding the lesion pattern of gastric damage after the administration of noxious agents.
This study investigates the mechanisms accounting for the adverse cholinergic effects of the antitumour drug irinotecan. The activity of irinotecan and its active metabolite, ...7‐ethyl‐10‐hydroxy‐camptothecin (SN‐38), was assayed in models suitable for pharmacological studies on cholinergic system.
Irinotecan moderately inhibited human or electric eel acetylcholinesterase activity, SN‐38 had no effect, whereas physostigmine blocked both the enzymes with high potency and efficacy.
Irinotecan and SN‐38 did not affect spontaneous or electrically‐induced contractile activity of human colonic muscle. Acetylcholine and dimethylphenylpiperazinium (DMPP) caused phasic contractions or relaxations, respectively. Physostigmine enhanced the motor responses elicited by electrical stimulation.
Although irinotecan and SN‐38 did not modify the basal contractile activity of guinea‐pig ileum longitudinal muscle strips, irinotecan 100 μM moderately enhanced cholinergic twitch contractions. Acetylcholine or DMPP caused phasic contractions, whereas physostigmine enhanced the twitch responses. Electrically‐induced 3H‐acetylcholine release was reduced by irinotecan (100 μM) or physostigmine (0.1 μM).
Intravenous irinotecan stimulated gastric acid secretion in rats, but no effects were obtained with SN‐38, physostigmine or i.c.v. irinotecan. Hypersecretion induced by irinotecan was partly prevented by ondansetron, and unaffected by capsazepine. In the presence of atropine, vagotomy and systemic or vagal ablation of capsaicin‐sensitive afferent fibres, irinotecan did not stimulate gastric secretion.
The present results indicate that irinotecan and SN‐38 do not act as specific acetylcholinesterase blockers or acetylcholine receptor agonists. It is rather suggested that irinotecan promotes a parasympathetic discharge to peripheral organs, mediated by capsaicin‐sensitive vagal afferent fibres, and that serotonin 5‐HT3 receptors are implicated in the genesis of vago‐vagal reflex triggered by irinotecan.
British Journal of Pharmacology (2001) 132, 73–84; doi:10.1038/sj.bjp.0703766
The protective effects of the proton pump inhibitor lansoprazole on gastric mucosal damage induced by ethanol-HCl or hemorrhagic shock were investigated in the present study. The morphometric ...analysis of gastric histological sections revealed that lansoprazole dose-dependently reduced mucosal injury evoked by ethanol-HCl (ED50 = 24.3 micromol/kg) or hemorrhagic shock (ED50 = 38.9 micromol/kg), these effects being associated with marked increments of Alcian blue recovery from gastric bound mucus (ED50 = 31.4 micromol/kg and 27.6 micromol/kg, respectively). In addition, lansoprazole inhibited gastric acid secretion from pylorus-ligated rats (ED50 = 9.8 micromol/kg). Further experiments, performed on rats with ethanol-HCl-induced gastric injury, indicated that the protective effects of lansoprazole were not modified by L-365,260, suramin, N(G)-nitro-L-arginine, or systemic ablation of capsaicin-sensitive sensory nerves, whereas they were partly blocked by indomethacin and fully prevented by N-ethyl-maleimide. In addition, lansoprazole did not modify somatostatin concentrations in gastric mucosa. The present results provide evidence that lansoprazole prevents the necrotic damage of gastric mucosa induced by ethanol-HCl or hemorrhagic shock. According to the rank order of ED50 values, these effects appear to depend mainly on the enhancement of the gastric mucus barrier rather than on the reduction of acid secretion. It is also proposed that an increased production of prostaglandins, as well as an increased availability of sulfhydryl compounds at level of gastric mucosa may account for the gastroprotective effects of lansoprazole.
Unhealthy eating behaviours increase with age and have been associated with adverse health consequences in adulthood. We examined the influence of screen-based sedentary behaviours (SBs) on unhealthy ...food consumption, such as energy-dense foods and sweetened drinks, among a representative sample of nearly 60 000 adolescents and assessed the role of possible modifiers.
Data come from the Italian 2009-10 Health Behaviour in School-aged Children (HBSC) survey. Data on Eating patterns, SBs, physical activity, peers network, BMI and socio-economic status (SES) were collected following the HBSC study protocol. Hierarchical logistic regression models were used.
Unhealthy food consumption was significantly associated with a lower intake of fruit and vegetables and with the increase of SBs in both sexes and in all ages. The risk was interestingly higher in normal weight adolescents, in those with wider relationships with peers and in low SES children.
This study adds evidence to support the importance of investing more resources in educational initiatives both to increase parents' awareness to support adolescents on dietary choices and on time spent in screen-based behaviours, independently of their adiposity status; and to develop youth's ability to access and appropriately use media and technologies. Policy makers should also increase their attention on introducing regulatory policies on television food advertising to which youth are exposed.
Mutation of genes encoding for various components of a metabolic pathway named the ubiquitin-proteasome system (UP) leads to inherited forms of Parkinson's disease (PD), whereas various components of ...the UP are constantly present within neuronal inclusions, Lewy bodies, that characterize most genetic and sporadic forms of PD. It has been hypothesized that impairment of this metabolic pathway might be a common mechanism for the onset of PD, and a recent study demonstrated a dysfunction of the UP system within the substantia nigra of patients affected by sporadic PD. In search for the mechanisms underlying the selective toxicity for nigral neurons after inhibition of the UP system, we explored the selective effects after striatal microinfusions of lactacystin or epoxomycin and potential retrograde changes within the ipsilateral substantia nigra. We found that neurotoxicity was selective for striatal dopamine (DA) components and led to retrograde apoptosis within nigral DA cells, which developed neuronal inclusions staining for antigens of the UP system. We found the same ultrastructural features characterizing inclusions obtained in vivo and in vitro after UP inhibition. In vivo, lactacystin-epoxomycin-induced toxicity was suppressed by inhibiting DA synthesis. Similarly, in vitro inclusions and apoptosis were prevented by reducing endogenous DA. On the other hand, toxicity of proteasome inhibition was enhanced by drugs augmenting DA availability: l-3,4-dihydroxyphenylalanine, monoamine oxidase blockers, and DA beta-hydroxylase blockers. These findings demonstrate that impairment of the UP system produces cell death and neuronal inclusions selectively for DA-containing neurons that depend on the occurrence of endogenous DA.
Objectives:
To examine overweight prevalence and its association with demographic and lifestyle factors in 11–15 year olds in the HBSC 2005–2006 survey.
Methods:
Self-reports of height, weight, ...eating patterns, physical activity and sedentary behaviours were obtained from nationally representative samples in 41 countries (n=204,534).
Results:
Overweight prevalence was highest in USA (28.8 %) and lowest in Latvia (7.6 %). In most countries, overweight was more prevalent in boys than girls. Overweight was consistently negatively associated with breakfast consumption and moderate to vigorous physical activity; OR range: 0.48–0.79 and 0.50–0.78, respectively.
Conclusion:
Overweight prevalence in youth remained high across the countries examined. The primary factors linked to overweight were breakfast consumption and physical activity. These data should contribute to formulating preventive programs and policies.
: The psychostimulant 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) is an amphetamine derivative that is widely abused. In previous studies, depending on the animal species, neurotoxicity has ...been demonstrated for either serotonin (5‐HT) or/and dopamine (DA) nerve endings. These studies focused on the basal ganglia circuitry; however, in humans chronic abuse of MDMA often results in neurological symptoms that last after MDMA withdrawal and are not related to the extrapyramidal system such as electroencephalographic (EEG) abnormalities and cognitive impairment. These alterations might be due to the concomitant intake of other illicit compounds, the consequence of MDMA‐induced hyperthermia, or to a primary neurotoxicity directed to extrastriatal regions. These observations call for a more in‐depth analysis on the potential involvement of brain areas outside the basal ganglia in the toxic effects induced primarily by MDMA. In the present study, we treated C57Black mice chronically (25 days) with daily injections of MDMA (2.5 mg/kg). During treatments, mice were monitored in order to detect behavioral modifications, and epidural electrodes were installed to perform EEG recording. Behavioral data showed a sensitization as measured by locomotor activity, which related to progressive and long‐lasting EEG changes and neuronal degeneration within the hippocampus.
Lewy bodies (LB) were first described by Lewy in 1912 1 as neuronal pale eosinophilic inclusions which became a pathological hallmark of Parkinson s disease (PD). In his original study, Lewy defined ...these inclusions as pale eosinophilic cytoplasmic structures, and studies since then have revealed LB to be ubiquitin-, alpha-synuclein-, and parkin-containing inclusions. This suggests that knowledge of the biochemical steps involved in the genesis of LB might disclose a final common pathway which might be responsible for different types of inherited and sporadic parkinsonism. This would lead to the identification of new therapeutic targets for interfering with disease progression. Although LB were originally described solely in PD, in the last decade these inclusions were described in a spectrum of degenerative disorders ranging from pure movement disorders to dementia. This suggests that common biochemical alterations leading to the formation of intracellular inclusions might underlie various pathological conditions. Consequently, the knowledge of the biochemical steps involved in the formation of neuronal inclusions could represent a key to develop new therapeutic strategies. In recent years it has been possible to develop both in vitro and in vivo neuronal inclusions resembling Lewy bodies. These experimental approaches have ranged from the use of alpha-synuclein transgenic mice to the continuous exposure to a mitochondrial complex I inhibitor. The aim of the present paper is to review briefly, recent advances on Lewy body research to achieve new insight into the etiology of PD and the molecular events leading to neurodegeneration.
To examine the association between adolescent at-risk or problem gambling (ARPG) and medicine used to treat nervousness in a large-scale nationally representative sample of Italian adolescents.
Data ...from the 2013/2014 Health Behaviour in School-aged Children Survey was used for cross-sectional analyses (a sample of 20,791 15-year-old students). Self-administered questionnaires were completed by a representative sample of high-school students. Respondents' ARPG, use of medicine for nervousness and potential confounding factors were assessed. Multilevel logistic regression analyses were used to test the association between medicine use to treat nervousness and ARPG.
The overall prevalence of adolescents reporting medicine use for nervousness in the last month was 6.3%. The odds of ARPG were 3 times higher among adolescents who used medicine for nervousness compared to that among adolescents who did not take such medicine (OR 2.96, 95% CI 2.07-4.25). Importantly, the association between medicine used to treat nervousness and ARPG did not vary significantly when viewed in light of psychological symptoms.
Medicine use to treat nervousness is associated with increased risk of gambling-related harm.
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