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  1. Irritable bowel syndrome, the microbiota and the gut-brain axis

    DEFF Research Database (Denmark)

    Raskov, Hans; Burcharth, Jakob; Pommergaard, Hans-Christian

    2016-01-01

    Irritable bowel syndrome is a common functional gastrointestinal disorder and it is now evident that irritable bowel syndrome is a multi-factorial complex of changes in microbiota and immunology. The bidirectional neurohumoral integrated communication between the microbiota and the autonomous...... nervous system is called the gut-brain-axis, which integrates brain and GI functions, such as gut motility, appetite and weight. The gut-brain-axis has a central function in the perpetuation of irritable bowel syndrome and the microbiota plays a critical role. The purpose of this article is to review...... recent research concerning the epidemiology of irritable bowel syndrome, influence of microbiota, probiota, gut-brain-axis, and possible treatment modalities on irritable bowel syndrome....

  2. Gut microbiota role in irritable bowel syndrome: New therapeutic strategies.

    Science.gov (United States)

    Distrutti, Eleonora; Monaldi, Lorenzo; Ricci, Patrizia; Fiorucci, Stefano

    2016-02-21

    In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gut microbiota, has provided support to the concept that a disturbed intestinal ecology might promote development and maintenance of symptoms in irritable bowel syndrome (IBS). As a correlate, manipulation of gut microbiota represents a new strategy for the treatment of this multifactorial disease. A number of attempts have been made to modulate the gut bacterial composition, following the idea that expansion of bacterial species considered as beneficial (Lactobacilli and Bifidobacteria) associated with the reduction of those considered harmful (Clostridium, Escherichia coli, Salmonella, Shigella and Pseudomonas) should attenuate IBS symptoms. In this conceptual framework, probiotics appear an attractive option in terms of both efficacy and safety, while prebiotics, synbiotics and antibiotics still need confirmation. Fecal transplant is an old treatment translated from the cure of intestinal infective pathologies that has recently gained a new life as therapeutic option for those patients with a disturbed gut ecosystem, but data on IBS are scanty and randomized, placebo-controlled studies are required.

  3. Irritable bowel syndrome: A microbiome-gut-brain axis disorder?

    Science.gov (United States)

    Kennedy, Paul J; Cryan, John F; Dinan, Timothy G; Clarke, Gerard

    2014-01-01

    Irritable bowel syndrome (IBS) is an extremely prevalent but poorly understood gastrointestinal disorder. Consequently, there are no clear diagnostic markers to help diagnose the disorder and treatment options are limited to management of the symptoms. The concept of a dysregulated gut-brain axis has been adopted as a suitable model for the disorder. The gut microbiome may play an important role in the onset and exacerbation of symptoms in the disorder and has been extensively studied in this context. Although a causal role cannot yet be inferred from the clinical studies which have attempted to characterise the gut microbiota in IBS, they do confirm alterations in both community stability and diversity. Moreover, it has been reliably demonstrated that manipulation of the microbiota can influence the key symptoms, including abdominal pain and bowel habit, and other prominent features of IBS. A variety of strategies have been taken to study these interactions, including probiotics, antibiotics, faecal transplantations and the use of germ-free animals. There are clear mechanisms through which the microbiota can produce these effects, both humoral and neural. Taken together, these findings firmly establish the microbiota as a critical node in the gut-brain axis and one which is amenable to therapeutic interventions. PMID:25339800

  4. Intestinal microbiome-gut-brain axis and irritable bowel syndrome.

    Science.gov (United States)

    Moser, Gabriele; Fournier, Camille; Peter, Johannes

    2018-03-01

    Psychological comorbidity is highly present in irritable bowel syndrome (IBS). Recent research points to a role of intestinal microbiota in visceral hypersensitivity, anxiety, and depression. Increased disease reactivity to psychological stress has been described too. A few clinical studies have attempted to identify features of dysbiosis in IBS. While animal studies revealed strong associations between stress and gut microbiota, studies in humans are rare. This review covers the most important studies on intestinal microbial correlates of psychological and clinical features in IBS, including stress, anxiety, and depression.

  5. Gut-directed hypnotherapy for functional abdominal pain or irritable bowel syndrome in children: a systematic review

    NARCIS (Netherlands)

    Rutten, Juliette M. T. M.; Reitsma, Johannes B.; Vlieger, Arine M.; Benninga, Marc A.

    2013-01-01

    Gut directed hypnotherapy (HT) is shown to be effective in adult functional abdominal pain (FAP) and irritable bowel syndrome (IBS) patients. We performed a systematic review to assess efficacy of HT in paediatric FAP/IBS patients. We searched Medline, Embase, PsychINFO, Cumulative Index to Nursing

  6. Evidence that independent gut-to-brain and brain-to-gut pathways operate in the irritable bowel syndrome and functional dyspepsia: a 1-year population-based prospective study.

    Science.gov (United States)

    Koloski, N A; Jones, M; Talley, N J

    2016-09-01

    Traditionally, functional gastrointestinal disorders (FGIDs) are conceptualised as originating in the brain via stress pathways (brain-to-gut). It is uncertain how many with irritable bowel syndrome (IBS) and functional dyspepsia (FD) have a gut origin of symptoms (gut-to-brain pathway). To determine if there is a distinct brain-to-gut FGID (where psychological symptoms begin first) and separately a distinct gut-to-brain FGID (where gut symptoms start first). A prospective random population sample from Newcastle, Australia who responded to a validated survey in 2012 and completed a 1-year follow-up survey (n = 1900). The surveys contained questions on Rome III IBS and FD and the Hospital Anxiety and Depression Scale. We found that higher levels of anxiety and depression at baseline were significant predictors of developing IBS (OR = 1.31; 95% CI 1.06-1.61, P = 0.01; OR = 1.54; 95% CI 1.29-1.83, P intestinal features in many cases. © 2016 John Wiley & Sons Ltd.

  7. The joint power of sex and stress to modulate brain-gut-microbiota axis and intestinal barrier homeostasis: implications for irritable bowel syndrome.

    Science.gov (United States)

    Pigrau, M; Rodiño-Janeiro, B K; Casado-Bedmar, M; Lobo, B; Vicario, M; Santos, J; Alonso-Cotoner, C

    2016-04-01

    Intestinal homeostasis is a dynamic process that takes place at the interface between the lumen and the mucosa of the gastrointestinal tract, where a constant scrutiny for antigens and toxins derived from food and microorganisms is carried out by the vast gut-associated immune system. Intestinal homeostasis is preserved by the ability of the mucus layer and the mucosal barrier to keep the passage of small-sized and antigenic molecules across the epithelium highly selective. When combined and preserved, immune surveillance and barrier's selective permeability, the host capacity of preventing the development of intestinal inflammation is optimized, and viceversa. In addition, the brain-gut-microbiome axis, a multidirectional communication system that integrates distant and local regulatory networks through neural, immunological, metabolic, and hormonal signaling pathways, also regulates intestinal function. Dysfunction of the brain-gut-microbiome axis may induce the loss of gut mucosal homeostasis, leading to uncontrolled permeation of toxins and immunogenic particles, increasing the risk of appearance of intestinal inflammation, mucosal damage, and gut disorders. Irritable bowel syndrome is prevalent stress-sensitive gastrointestinal disorder that shows a female predominance. Interestingly, the role of stress, sex and gonadal hormones in the regulation of intestinal mucosal and the brain-gut-microbiome axis functioning is being increasingly recognized. We aim to critically review the evidence linking sex, and stress to intestinal barrier and brain-gut-microbiome axis dysfunction and the implications for irritable bowel syndrome. © 2015 John Wiley & Sons Ltd.

  8. Stress and the Microbiota-Gut-Brain Axis in Visceral Pain: Relevance to Irritable Bowel Syndrome.

    Science.gov (United States)

    Moloney, Rachel D; Johnson, Anthony C; O'Mahony, Siobhain M; Dinan, Timothy G; Greenwood-Van Meerveld, Beverley; Cryan, John F

    2016-02-01

    Visceral pain is a global term used to describe pain originating from the internal organs of the body, which affects a significant proportion of the population and is a common feature of functional gastrointestinal disorders (FGIDs) such as irritable bowel syndrome (IBS). While IBS is multifactorial, with no single etiology to completely explain the disorder, many patients also experience comorbid behavioral disorders, such as anxiety or depression; thus, IBS is described as a disorder of the gut-brain axis. Stress is implicated in the development and exacerbation of visceral pain disorders. Chronic stress can modify central pain circuitry, as well as change motility and permeability throughout the gastrointestinal (GI) tract. More recently, the role of the gut microbiota in the bidirectional communication along the gut-brain axis, and subsequent changes in behavior, has emerged. Thus, stress and the gut microbiota can interact through complementary or opposing factors to influence visceral nociceptive behaviors. This review will highlight the evidence by which stress and the gut microbiota interact in the regulation of visceral nociception. We will focus on the influence of stress on the microbiota and the mechanisms by which microbiota can affect the stress response and behavioral outcomes with an emphasis on visceral pain. © 2015 John Wiley & Sons Ltd.

  9. Role of gut pathogens in development of irritable bowel syndrome

    Directory of Open Access Journals (Sweden)

    Madhusudan Grover

    2014-01-01

    Full Text Available Acute infectious gastroenteritis is one of the most commonly identifiable risk factors for the development of irritable bowel syndrome (IBS. A number of bacterial, viral and parasitic pathogens have been found to be associated with the development of IBS and other functional gastrointestinal (GI disorders. Epidemiological studies have identified demographic and acute enteritis-related risk factors for the development of post-infectious-IBS (PI-IBS. Immune dysregulation, alterations in barrier function, serotonergic and mast cell activation have been identified as potential pathophysiological mechanisms. Additionally, variations in host genes involved in barrier function, antigen presentation and cytokine response have been associated with PI-IBS development. However, it is unknown whether specific pathogens have unique effects on long-term alterations in gut physiology or different pathogens converge to cause common alterations resulting in similar phenotype. The role of microbial virulence and pathogenicity factors in development of PI-IBS is also largely unknown. Additionally, alterations in host gut sensation, motility, secretion, and barrier function in PI-IBS need to be elucidated. Finally, both GI infections and antibiotics used to treat these infections can cause long-term alterations in host commensal microbiota. It is plausible that alteration in the commensal microbiome persists in a subset of patients predisposing them to develop PI-IBS.

  10. No Change in Rectal Sensitivity After Gut-Directed Hypnotherapy in Children With Functional Abdominal Pain or Irritable Bowel Syndrome

    NARCIS (Netherlands)

    Vlieger, A. M.; van den Berg, M. M.; Menko-Frankenhuis, C.; Bongers, M. E. J.; Tromp, E.; Benninga, M. A.

    2010-01-01

    OBJECTIVES: Gut-directed hypnotherapy (HT) has recently been shown to be highly effective in treating children with functional abdominal pain (FAP) and irritable bowel syndrome (IBS). This study was conducted to determine the extent to which this treatment success is because of an improvement in

  11. Patient satisfaction after gut-directed hypnotherapy in irritable bowel syndrome.

    Science.gov (United States)

    Lindfors, P; Ljótsson, B; Bjornsson, E; Abrahamsson, H; Simrén, M

    2013-02-01

    Gut-directed hypnotherapy is an effective treatment option for irritable bowel syndrome (IBS). However, clinical observations suggest that patient satisfaction with hypnotherapy is not always associated with improvement in IBS symptoms. We evaluated 83 patients with IBS treated with gut-directed hypnotherapy (1 h week(-1), 12 weeks). After the treatment period, patients reported their satisfaction with the treatment (ranging from 1 = not at all satisfied, to 5 = very satisfied) and completed questionnaires to assess IBS symptom severity, quality of life, cognitive function, sense of coherence, depression, and anxiety before and after treatment. After hypnotherapy improved IBS symptom severity, quality of life, cognitive function, and anxiety were seen. Thirty patients (36%) were very satisfied with the treatment and 57 (69%) patients scored 4 or 5 on the patient satisfaction scale. Patient satisfaction was associated with less severe IBS symptoms and better quality of life after the treatment. In a multiple linear regression analysis, only the quality of life domain sexual relations was independently associated with patient satisfaction after hypnotherapy, explaining 22% of the variance. Using 25% reduction of IBS symptom severity to define an IBS symptom responder, 52% of the responders were very satisfied with hypnotherapy, but this was also true for 31% in the non-responder group. Patient satisfaction with gut-directed hypnotherapy in IBS is associated with improvement of quality of life and gastrointestinal (GI) symptoms. However, other factors unrelated to GI symptoms also seems to be of importance for patient satisfaction, as a substantial proportion of patients without GI symptom improvement were also very satisfied with this treatment option. © 2012 Blackwell Publishing Ltd.

  12. Review article: gut-directed hypnotherapy in the management of irritable bowel syndrome and inflammatory bowel disease.

    Science.gov (United States)

    Peters, S L; Muir, J G; Gibson, P R

    2015-06-01

    Gut-directed hypnotherapy is being increasingly applied to patients with irritable bowel syndrome (IBS) and to a lesser extent, inflammatory bowel disease (IBD). To review the technique, mechanisms of action and evidence for efficacy, and to identify gaps in the understanding of gut-directed hypnotherapy as a treatment for IBS and IBD. A review of published literature and a systematic review of clinical trials in its application to patients with IBS and IBD were performed. Gut-directed hypnotherapy is a clearly described technique. Its potential mechanisms of action on the brain-gut axis are multiple with evidence spanning psychological effects through to physiological gastrointestinal modifications. Six of seven randomised IBS studies reported a significant reduction (all P hypnotherapy ranged between 24% and 73%. Efficacy was maintained long-term in four of five studies. A therapeutic effect was also observed in the maintenance of clinical remission in patients with ulcerative colitis. Uncontrolled trials supported the efficacy and durability of gut-directed hypnotherapy in IBS. Gaps in understanding included to whom and when it should be applied, the paucity of adequately trained hypnotherapists, and the difficulties in designing well controlled-trials. Gut-directed hypnotherapy has durable efficacy in patients with IBS and possibly ulcerative colitis. Whether it sits in the therapeutic arsenal as a primary and/or adjunctive therapy cannot be ascertained on the current evidence base. Further research into efficacy, mechanisms of action and predictors of response is required. © 2015 John Wiley & Sons Ltd.

  13. Long-Term Follow-Up of Gut-Directed Hypnotherapy vs. Standard Care in Children With Functional Abdominal Pain or Irritable Bowel Syndrome

    NARCIS (Netherlands)

    Vlieger, Arine M.; Rutten, Juliette M. T. M.; Govers, Anita M. A. P.; Frankenhuis, Carla; Benninga, Marc A.

    2012-01-01

    OBJECTIVES: We previously showed that gut-directed hypnotherapy (HT) is highly effective in the treatment of children with functional abdominal pain (FAP) and irritable bowel syndrome (IBS). Aim of this follow-up study was to investigate the long-term effects of HT vs. standard medical treatment

  14. Cholinergic signalling in gut immunity

    NARCIS (Netherlands)

    Dhawan, Shobhit; Cailotto, Cathy; Harthoorn, Lucien F.; de Jonge, Wouter J.

    2012-01-01

    The gut immune system shares many signalling molecules and receptors with the autonomic nervous system. A good example is the vagal neurotransmitter acetylcholine (ACh), for which many immune cell types express cholinergic receptors (AChR). In the last decade the vagal nerve has emerged as an

  15. Effects on gastrointestinal transit and antroduodenojejunal manometry after gut-directed hypnotherapy in irritable bowel syndrome (IBS).

    Science.gov (United States)

    Lindfors, Perjohan; Törnblom, Hans; Sadik, Riadh; Björnsson, Einar S; Abrahamsson, Hasse; Simrén, Magnus

    2012-12-01

    Gut-directed hypnotherapy is an effective treatment in irritable bowel syndrome (IBS) but little is known about the mechanisms of action. In this study we aimed to investigate the effects on gastrointestinal motility when treating IBS with gut-directed hypnotherapy. We randomized 90 patients with IBS, refractory to standard management to receive gut-directed hypnotherapy 1 h/week for 12 weeks or supportive treatment for the same time period. Eighty-one subjects (40 hypnotherapy, 41 controls) could be evaluated by one or more of the following investigations, both before and after the intervention: gastric emptying time, small bowel transit time, colonic transit time, and antroduodenojejunal manometry. No significant differences in gastric emptying time, small bowel transit time, or colonic transit time was found when comparing the baseline and post-intervention measurements in the hypnotherapy group or in the control group. The same was true concerning the results of the antroduodenojejunal manometry. However, there was a numerical trend toward a higher number of migrating motor complexes at manometry and an accelerated gastric emptying time after hypnotherapy that did not reach statistical significance. In this study, we were not able to find evidence for long-standing effects on gastrointestinal motility as a mediator of the effects on IBS when treating the condition with gut-directed hypnotherapy. Further research to understand the mechanism of action is needed.

  16. Randomised clinical trial: Gut microbiome biomarkers are associated with clinical response to a low FODMAP diet in children with the irritable bowel syndrome

    Science.gov (United States)

    A low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet can ameliorate symptoms in adult irritable bowel syndrome (IBS) within 48 h. To determine the efficacy of a low FODMAP diet in childhood IBS and whether gut microbial composition and/or metabolic capacity ar...

  17. Pathogenesis, Experimental Models and Contemporary Pharmacotherapy of Irritable Bowel Syndrome: Story About the Brain-Gut Axis

    Science.gov (United States)

    Tsang, S.W.; Auyeung, K.K.W.; Bian, Z.X.; Ko, J.K.S.

    2016-01-01

    Background Although the precise pathophysiology of irritable bowel syndrome (IBS) remains unknown, it is generally considered to be a disorder of the brain-gut axis, representing the disruption of communication between the brain and the digestive system. The present review describes advances in understanding the pathophysiology and experimental approaches in studying IBS, as well as providing an update of the therapies targeting brain-gut axis in the treatment of the disease. Methods Causal factors of IBS are reviewed. Following this, the preclinical experimental models of IBS will be introduced. Besides, both current and future therapeutic approaches of IBS will be discussed. Results When signal of the brain-gut axis becomes misinterpreted, it may lead to dysregulation of both central and enteric nervous systems, altered intestinal motility, increased visceral sensitivity and consequently contributing to the development of IBS. Interference of the brain-gut axis can be modulated by various psychological and environmental factors. Although there is no existing animal experiment that can represent this complex multifactorial disease, these in vivo models are clinically relevant readouts of gastrointestinal functions being essential to the identification of effective treatments of IBS symptoms as well as their molecular targets. Understanding the brain-gut axis is essential in developing the effective therapy for IBS. Therapies include improvement of GI motor functions, relief of visceral hypersensitivity and pain, attenuation of autonomic dysfunctions and suppression of mucosal immune activation. Conclusion Target-oriented therapies that provide symptomatic, psychological and physiological benefits could surely help to improve the quality of life of IBS patients. PMID:27009115

  18. The Gut-Brain Axis and the Microbiome: Clues to Pathophysiology and Opportunities for Novel Management Strategies in Irritable Bowel Syndrome (IBS

    Directory of Open Access Journals (Sweden)

    Eamonn M.M. Quigley

    2018-01-01

    Full Text Available Irritable bowel syndrome (IBS is one of the most common of all medical disorders worldwide and, while for some it represents no more than a nuisance, for others it imposes significant negative impacts on daily life and activities. IBS is a heterogeneous disorder and may well have a number of causes which may lie anywhere from the external environment to the contents of the gut lumen and from the enteric neuromuscular apparatus and the gut immune system to the central nervous system. Consequently, the paradigm of the gut-brain axis, which includes the participation of these various factors, has proven a useful model to assist clinicians and patients alike in understanding the genesis of symptoms in IBS. Now, given the widespread interest in the gut microbiome in health and disease, in general, reports of disordered enteric bacterial communities in IBS, and experimental data to indicate that components of the gut microbiota can influence brain morphology and function, as well as behavior and cognition, this concept has been extended to encompass the microbiota-gut-brain axis. The implications of this novel concept to the assessment and management of IBS will be explored in this review.

  19. Irritable bowel syndrome: contemporary nutrition management strategies.

    Science.gov (United States)

    Mullin, Gerard E; Shepherd, Sue J; Chander Roland, Bani; Ireton-Jones, Carol; Matarese, Laura E

    2014-09-01

    Irritable bowel syndrome is a complex disorder whose pathophysiology involves alterations in the enteric microbiota, visceral hypersensitivity, gut immune/barrier function, hypothalamic-pituitary-adrenal axis regulation, neurotransmitters, stress response, psychological factors, and more. The importance of diet in the management of irritable bowel syndrome has taken center stage in recent times as the literature validates the relationship of certain foods with the provocation of symptoms. Likewise, a number of elimination dietary programs have been successful in alleviating irritable bowel syndrome symptoms. Knowledge of the dietary management strategies for irritable bowel syndrome will help guide nutritionists and healthcare practitioners to deliver optimal outcomes. This tutorial reviews the nutrition management strategies for irritable bowel syndrome. © 2014 American Society for Parenteral and Enteral Nutrition.

  20. Gut-directed hypnotherapy in children with irritable bowel syndrome or functional abdominal pain (syndrome): A randomized controlled trial on self exercises at home using CD versus individual therapy by qualified therapists

    NARCIS (Netherlands)

    J.M.T.M. Rutten (Juliette); A.M. Vlieger (Arine M.); C. Frankenhuis (Carla); E.K. George (Elvira K.); M. Groeneweg (Michael); O.F. Norbruis (Obbe); W.E. Tjon A ten; H. Van Wering (Herbert); M.G.W. Dijkgraaf (Marcel); M.P. Merkus; M.A. Benninga (Marc)

    2014-01-01

    textabstractBackground: Irritable bowel syndrome (IBS) and functional abdominal pain (syndrome) (FAP(S)) are common pediatric disorders, characterized by chronic or recurrent abdominal pain. Treatment is challenging, especially in children with persisting symptoms. Gut-directed hypnotherapy (HT)

  1. Ecophysiological consequences of alcoholism on human gut microbiota: implications for ethanol-related pathogenesis of colon cancer.

    Science.gov (United States)

    Tsuruya, Atsuki; Kuwahara, Akika; Saito, Yuta; Yamaguchi, Haruhiko; Tsubo, Takahisa; Suga, Shogo; Inai, Makoto; Aoki, Yuichi; Takahashi, Seiji; Tsutsumi, Eri; Suwa, Yoshihide; Morita, Hidetoshi; Kinoshita, Kenji; Totsuka, Yukari; Suda, Wataru; Oshima, Kenshiro; Hattori, Masahira; Mizukami, Takeshi; Yokoyama, Akira; Shimoyama, Takefumi; Nakayama, Toru

    2016-06-13

    Chronic consumption of excess ethanol increases the risk of colorectal cancer. The pathogenesis of ethanol-related colorectal cancer (ER-CRC) is thought to be partly mediated by gut microbes. Specifically, bacteria in the colon and rectum convert ethanol to acetaldehyde (AcH), which is carcinogenic. However, the effects of chronic ethanol consumption on the human gut microbiome are poorly understood, and the role of gut microbes in the proposed AcH-mediated pathogenesis of ER-CRC remains to be elaborated. Here we analyse and compare the gut microbiota structures of non-alcoholics and alcoholics. The gut microbiotas of alcoholics were diminished in dominant obligate anaerobes (e.g., Bacteroides and Ruminococcus) and enriched in Streptococcus and other minor species. This alteration might be exacerbated by habitual smoking. These observations could at least partly be explained by the susceptibility of obligate anaerobes to reactive oxygen species, which are increased by chronic exposure of the gut mucosa to ethanol. The AcH productivity from ethanol was much lower in the faeces of alcoholic patients than in faeces of non-alcoholic subjects. The faecal phenotype of the alcoholics could be rationalised based on their gut microbiota structures and the ability of gut bacteria to accumulate AcH from ethanol.

  2. Gut-directed hypnotherapy in children with irritable bowel syndrome or functional abdominal pain (syndrome): a randomized controlled trial on self exercises at home using CD versus individual therapy by qualified therapists

    NARCIS (Netherlands)

    Rutten, Juliette M. T. M.; Vlieger, Arine M.; Frankenhuis, Carla; George, Elvira K.; Groeneweg, Michael; Norbruis, Obbe F.; Tjon A ten, Walther; van Wering, Herbert; Dijkgraaf, Marcel G. W.; Merkus, Maruschka P.; Benninga, Marc A.

    2014-01-01

    Irritable bowel syndrome (IBS) and functional abdominal pain (syndrome) (FAP(S)) are common pediatric disorders, characterized by chronic or recurrent abdominal pain. Treatment is challenging, especially in children with persisting symptoms. Gut-directed hypnotherapy (HT) performed by a therapist

  3. Management of Irritable Bowel Syndrome: Novel Approaches to the Pharmacology of Gut Motility

    Directory of Open Access Journals (Sweden)

    Carmelo Scarpignato

    1999-01-01

    Full Text Available Although it is unclear to what extent irritable bowel syndrome (IBS symptoms represent a normal perception of abnormal function or an abnormal perception of normal function, many believe that IBS constitutes the clinical expression of an underlying motility disorder, affecting primarily the mid- and lower gut. Indeed, transit and contractile abnormalities have been demonstrated with sophisticated techniques in a subset of patients with IBS. As a consequence, drugs affecting gastrointestinal (GI motility have been widely employed with the aim of correcting the major IBS manifestations, ie, pain and altered bowel function. Unfortunately, no single drug has proven to be effective in treating IBS symptom complex. In addition, the use of some medications has often been associated with unpleasant side effects. Therefore, the search for a truly effective and safe drug to control motility disturbances in IBS continues. Several classes of drugs look promising and are under evaluation. Among the motor- inhibiting drugs, gut selective muscarinic antagonists (such as zamifenacin and darifenacin, neurokinin2 antagonists (such as MEN-10627 and MEN-11420, beta3-adrenoreceptor agonists (eg, SR-58611A and GI-selective calcium channel blockers (eg, pinaverium bromide and octylonium are able to decrease painful contractile activity in the gut (antispasmodic effect, without significantly affecting other body functions. Novel mechanisms to stimulate GI motility and transit include blockade of cholecystokinin (CCKA receptors and stimulation of motilin receptors. Loxiglumide (and its dextroisomer, dexloxiglumide is the only CCKA receptor antagonist that is being evaluated clinically. This drug accelerates gastric emptying and colonic transit, thereby increasing the number of bowel movements in patients with chronic constipation. It is also able to reduce visceral perception. Erythromycin and related 14-member macrolide compounds inhibit the binding of motilin to its

  4. Gut inflammation in chronic fatigue syndrome

    OpenAIRE

    Lakhan, Shaheen E; Kirchgessner, Annette

    2010-01-01

    Abstract Chronic fatigue syndrome (CFS) is a debilitating disease characterized by unexplained disabling fatigue and a combination of accompanying symptoms the pathology of which is incompletely understood. Many CFS patients complain of gut dysfunction. In fact, patients with CFS are more likely to report a previous diagnosis of irritable bowel syndrome (IBS), a common functional disorder of the gut, and experience IBS-related symptoms. Recently, evidence for interactions between the intestin...

  5. Impact of psychological stress on irritable bowel syndrome.

    Science.gov (United States)

    Qin, Hong-Yan; Cheng, Chung-Wah; Tang, Xu-Dong; Bian, Zhao-Xiang

    2014-10-21

    Psychological stress is an important factor for the development of irritable bowel syndrome (IBS). More and more clinical and experimental evidence showed that IBS is a combination of irritable bowel and irritable brain. In the present review we discuss the potential role of psychological stress in the pathogenesis of IBS and provide comprehensive approaches in clinical treatment. Evidence from clinical and experimental studies showed that psychological stresses have marked impact on intestinal sensitivity, motility, secretion and permeability, and the underlying mechanism has a close correlation with mucosal immune activation, alterations in central nervous system, peripheral neurons and gastrointestinal microbiota. Stress-induced alterations in neuro-endocrine-immune pathways acts on the gut-brain axis and microbiota-gut-brain axis, and cause symptom flare-ups or exaggeration in IBS. IBS is a stress-sensitive disorder, therefore, the treatment of IBS should focus on managing stress and stress-induced responses. Now, non-pharmacological approaches and pharmacological strategies that target on stress-related alterations, such as antidepressants, antipsychotics, miscellaneous agents, 5-HT synthesis inhibitors, selective 5-HT reuptake inhibitors, and specific 5-HT receptor antagonists or agonists have shown a critical role in IBS management. A integrative approach for IBS management is a necessary.

  6. Research of small quaternary AChE inhibitors as pretreatment of OP poisoning

    International Nuclear Information System (INIS)

    Musilek, K.; Komloova, M.; Holas, O.; Opletalova, V.; Pohanka, M.; Kuca, K.

    2009-01-01

    Small quaternary AChE inhibitors are used (e.g. pyridostigmine) or scoped (e.g. SAD-128) for pretreatment against organophosphate intoxication [1]. The pretreatment is based on competitive inhibition of AChE prior to organophosphate (OP) poisoning. Consequently, the OP can not influence the inhibited AChE and is degraded by other esterases. Although various competitive inhibitors are used globally, pyridostigmine still remains the most broaden. Its side effects including gastrointestinal effects (nausea, intestinal obstruction), increased bronchial secretion, cardiac arrhythmia or cholinergic crisis are well described. Moreover, some bisquaternary competitive inhibitors (e.g. SAD-128) were used to decrease lethal effects of OP poisoning in vivo. The further studies dealing with SAD-128 showed its increased ability to interact with brain muscarinic acetylcholine receptors as allosteric inhibitors [2]. The small molecules derived from quaternized pyridine, quinoline and isoquinoline were designed as AChE inhibitors. Their ability to inhibit AChE or BChE was determined in vitro using IC50. The IC50 data were compared within each group of compounds with emphasis on selectivity AChE versus BChE. The overall study will be presented. The work was supported by Ministry of Defence of Czech Republic No. OVUOFVZ200805.(author)

  7. Measurement of acetylcholinesterase (AChE) activity in living brain by positron emission tomography (PET)

    Energy Technology Data Exchange (ETDEWEB)

    Irie, Toshiaki [National Inst. of Radiological Sciences, Chiba (Japan)

    1999-07-01

    Central cholinergic neuronal system has been known to be related to learning and memory, and its deficit is found in the brain of Alzheimer's disease (AD) and other degenerative disorders. Postmortem studies have shown that acetylcholinesterase (AChE), one of biochemical markers of central cholinergic nerve system, is consistently reduced in the cerebral cortex of patients with Alzheimer's disease (AD). Non-invasive mapping and/or measuring AChE activity in the living brain by positron emission tomography (PET) would be a useful tool for assessment of cholinergic dysfunction in AD and other disorders, and provide a direct method for validation of therapeutic efficacy of drugs, AChE inhibitors. We have challenged to measure AChE activity using tracers of substrate type, radiolabelled acetylcholine analogs, which are lipophilic enough to go across blood brain barrier and are metabolically trapped by AChE in the brain. The analogs designed, N-methylpiperidyl esters, were evaluated in terms of their metabolic rate and specificity against AChE. Studies examining the response to AChE activity showed metabolic accumulation of some analogs responded well to changes in cortical AChE activity in an animal model of AD. The study was further applied to living human by PET using [{sup 11}C]N-methylpiperidyl-4-acetate (MP4A), which was chosen on the basis of its reactivity and specificity suitable for the human cortical AChE. Regional cerebral metabolic rate of MP4A reflecting AChE activity was quantitatively determined using three compartment model analysis of dynamic PET data and the arterial input function obtained by TLC-radioluminography or plasma samples. The kinetic analyses showed that AChE activities estimated were well agree with those of postmortem examination in cerebral cortices and thalamus in healthy subjects, and that there was significant reduction of cortical AChE activity in patients with AD. The results suggest feasibility of the present method for

  8. Centrally Acting Oximes in Reactivation of Tabun-Phosphoramidated AChE

    Science.gov (United States)

    Kovarik, Zrinka; Maček, Nikolina; Sit, Rakesh K.; Radić, Zoran; Fokin, Valery V.; Sharpless, K. Barry; Taylor, Palmer

    2012-01-01

    Organophosphates (OP) inhibit acetylcholinesterase (AChE, E.C.3.1.1.7), both in peripheral tissues and central nervous system (CNS), causing adverse and sometimes fatal effects due to the accumulation of neurotransmitter acetylcholine (ACh). The currently used therapy, focusing on the reactivation of inhibited AChE, is limited to peripheral tissues because commonly used quaternary pyridinium oxime reactivators do not cross the blood brain barrier (BBB) at therapeutically relevant levels. A directed library of thirty uncharged oximes that contain tertiary amine or imidazole protonable functional groups that should cross the BBB as unionized species was tested as tabun-hAChE conjugate reactivators along with three reference oximes: DAM (diacetylmonoxime), MINA (monoisonitrosoacetone), and 2-PAM. The oxime RS150D [N-((1-(3-(2-((hydroxyimino)methyl)-1H-imidazol-1-yl)propyl)-1H-1,2,3-triazol-4-yl)methyl)benzamide] was highlighted as the most promising reactivator of the tabun-hAChE conjugate. We also observed that oximes RS194B [N-(2-(azepan-1-yl)ethyl)-2-(hydroxyimino)acetamide] and RS41A [2-(hydroxyimino)-N-(2-(pyrrolidin-1-yl)ethyl)acetamide], which emerged as lead uncharged reactivators of phosphylated hAChE with other OPs (sarin, cyclosarin and VX), exhibited only moderate reactivation potency for tabun inhibited hAChE. This implies that geometry of oxime access to the phosphorus atom conjugated to the active serine is an important criterion for efficient reactivation, along with the chemical nature of the conjugated moiety: phosphorate, phosphonate, or phosphoramidate. Moreover, modification of the active center through mutagenesis enhances the rates of reactivation. The phosphoramidated-hAChE choline-binding site mutant Y337A showed three-times enhanced reactivation capacity with non-triazole imidazole containing aldoximes (RS113B, RS113A and RS115A) and acetamide derivative (RS194B) than with 2PAM. PMID:22960624

  9. Curcumin attenuates collagen-induced inflammatory response through the "gut-brain axis".

    Science.gov (United States)

    Dou, Yannong; Luo, Jinque; Wu, Xin; Wei, Zhifeng; Tong, Bei; Yu, Juntao; Wang, Ting; Zhang, Xinyu; Yang, Yan; Yuan, Xusheng; Zhao, Peng; Xia, Yufeng; Hu, Huijuan; Dai, Yue

    2018-01-06

    Previous studies have demonstrated that oral administration of curcumin exhibited an anti-arthritic effect despite its poor bioavailability. The present study aimed to explore whether the gut-brain axis is involved in the therapeutic effect of curcumin. The collagen-induced arthritis (CIA) rat model was induced by immunization with an emulsion of collagen II and complete Freund's adjuvant. Sympathetic and parasympathetic tones were measured by electrocardiographic recordings. Unilateral cervical vagotomy (VGX) was performed before the induction of CIA. The ChAT, AChE activities, and serum cytokine levels were determined by ELISA. The expression of the high-affinity choline transporter 1 (CHT1), ChAT, and vesicular acetylcholine transporter (VAChT) were determined by real-time PCR and immunohistochemical staining. The neuronal excitability of the vagus nerve was determined by whole-cell patch clamp recording. Oral administration of curcumin restored the imbalance between the sympathetic and parasympathetic tones in CIA rats and increased ChAT activity and expression of ChAT and VAChT in the gut, brain, and synovium. Additionally, VGX eliminated the effects of curcumin on arthritis and ACh biosynthesis and transport. Electrophysiological data showed that curcumin markedly increased neuronal excitability of the vagus nerve. Furthermore, selective α7 nAChR antagonists abolished the effects of curcumin on CIA. Our results demonstrate that curcumin attenuates CIA through the "gut-brain axis" by modulating the function of the cholinergic system. These findings provide a novel approach for mechanistic studies of anti-arthritic compounds with low oral absorption and bioavailability.

  10. Preliminary Screening a Potential AChE Inhibitor in Thai Golden Shower (Leguminosae mimosoideae Extracts

    Directory of Open Access Journals (Sweden)

    Jakkaphun Nanuam

    2013-07-01

    Full Text Available Pesticides are used to control pests of agriculture products in many countries including Thailand. Since they can exert harmful effects not only on target pests but also on other useful organisms, alternative agents are investigated. We studied the capacity of the Thai golden shower (Leguminosae mimosoideae extracts (root and pod to inhibit acetyl cholinestarese (AChE in the golden apple snail (Pomacea canaliculata as a pest representative. The results showed that the percentage of AChE inhibition increased with increasing in exposure times. The inhibition expressed the same trend in both male and female apple snails. AChE inhibition was higher in extracts from root than from pod. Chromatography-Mass Spectrometer (GC-MS chromatograms demonstrated anthraquinone, an AChE inhibitor, in extracts of golden shower. Our data indicate that a potential AChE inhibitor tends to accumulate more in the root part than in the pod.

  11. Natural AChE Inhibitors from Plants and their Contribution to Alzheimer's Disease Therapy.

    Science.gov (United States)

    Murray, Ana Paula; Faraoni, María Belén; Castro, María Julia; Alza, Natalia Paola; Cavallaro, Valeria

    2013-07-01

    As acetylcholinesterase (AChE) inhibitors are an important therapeutic strategy in Alzheimer's disease, efforts are being made in search of new molecules with anti-AChE activity. The fact that naturally-occurring compounds from plants are considered to be a potential source of new inhibitors has led to the discovery of an important number of secondary metabolites and plant extracts with the ability of inhibiting the enzyme AChE, which, according to the cholinergic hypothesis, increases the levels of the neurotransmitter acetylcholine in the brain, thus improving cholinergic functions in patients with Alzheimer's disease and alleviating the symptoms of this neurological disorder. This review summarizes a total of 128 studies which correspond to the most relevant research work published during 2006-2012 (1st semester) on plant-derived compounds, plant extracts and essential oils found to elicit AChE inhibition.

  12. Changing face of irritable bowel syndrome

    Institute of Scientific and Technical Information of China (English)

    Eamonn MM Quigley

    2006-01-01

    Recent years have witnessed tremendous progress in our understanding of irritable bowel syndrome (IBS). It is evident that this is a truly global disease associated with significant symptoms and impairments in personal and social functioning for afflicted individuals. Advances in our understanding of gut flora-mucosal interactions, the enteric nervous system and the brain-gut axis have led to substantial progress in the pathogenesis of symptoms in IBS and have provided some hints towards the basic etiology of this disorder, in some subpopulations, at the very least. We look forward to a time when therapy will be addressed to pathophysiology and perhaps, even to primary etiology. In the meantime, a model based on a primary role for intestinal inflammation serves to integrate the various strands, which contribute to the presentation of IBS

  13. Natural AChE Inhibitors from Plants and their Contribution to Alzheimer’s Disease Therapy

    OpenAIRE

    Murray, Ana Paula; Faraoni, María Belén; Castro, María Julia; Alza, Natalia Paola; Cavallaro, Valeria

    2013-01-01

    As acetylcholinesterase (AChE) inhibitors are an important therapeutic strategy in Alzheimer’s disease, efforts are being made in search of new molecules with anti-AChE activity. The fact that naturally-occurring compounds from plants are considered to be a potential source of new inhibitors has led to the discovery of an important number of secondary metabolites and plant extracts with the ability of inhibiting the enzyme AChE, which, according to the cholinergic hypothesis, increases the le...

  14. The Role of Mast Cells in Irritable Bowel Syndrome

    OpenAIRE

    Lee, Kang Nyeong; Lee, Oh Young

    2016-01-01

    Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, but its treatment is unsatisfactory as its pathophysiology is multifactorial. The putative factors of IBS pathophysiology are visceral hypersensitivity and intestinal dysmotility, also including psychological factors, dysregulated gut-brain axis, intestinal microbiota alterations, impaired intestinal permeability, and mucosal immune alterations. Recently, mucosal immune alterations have received mu...

  15. Altered gastric emptying in patients with irritable bowel syndrome

    International Nuclear Information System (INIS)

    Caballero-Plasencia, A.M.; Valenzuela-Barranco, M.; Herrerias-Gutierrez, J.M.; Esteban-Carretero, J.M.

    1999-01-01

    Irritable bowel syndrome is the most frequent functional disorder of the digestive system. Patients with irritable bowel syndrome have motor disorders not only in the colon, but also in other parts of the digestive tract such as the oesophagus and small intestine; however, it is not known whether the stomach is also involved. We used a radiolabelled mixed solid-liquid meal (technetium-99m for the solid component, indium-111 for the liquid component) to study gastric emptying of solids (GES), liquids (GEL) and indigestible solids (GER) in 50 patients diagnosed as having irritable bowel syndrome (30 with predominant constipation and 20 with predominant diarrhoea). GER was measured by counting the number of indigestible solids remaining in the stomach 4 h after they were swallowed. In patients with irritable bowel syndrome, GES and GEL were slower than in control subjects (P<0.05). GER was normal in all patients except for two women. Thirty-two patients (64%) showed delayed GES, 29 (58%) delayed GEL, and 2 (4%) delayed GER. Among patients with irritable bowel syndrome, GES was slower in those with predominant constipation than in those with predominant diarrhoea (P<0.05); GEL and GER were similar in both groups. Gastroparesis was found in a large proportion of patients with irritable bowel syndrome, suggesting the presence of a more generalised motor disorder of the gut. (orig.)

  16. Probiotics and irritable bowel syndrome.

    Science.gov (United States)

    Dai, Cong; Zheng, Chang-Qing; Jiang, Min; Ma, Xiao-Yu; Jiang, Li-Juan

    2013-09-28

    Irritable bowel syndrome (IBS) is common gastrointestinal problems. It is characterized by abdominal pain or discomfort, and is associated with changes in stool frequency and/or consistency. The etiopathogenesis of IBS may be multifactorial, as is the pathophysiology, which is attributed to alterations in gastrointestinal motility, visceral hypersensitivity, intestinal microbiota, gut epithelium and immune function, dysfunction of the brain-gut axis or certain psychosocial factors. Current therapeutic strategies are often unsatisfactory. There is now increasing evidence linking alterations in the gastrointestinal microbiota and IBS. Probiotics are living organisms which, when ingested in certain numbers, exert health benefits beyond inherent basic nutrition. Probiotics have numerous positive effects in the gastrointestinal tract. Recently, many studies have suggested that probiotics are effective in the treatment of IBS. The mechanisms of probiotics in IBS are very complex. The purpose of this review is to summarize the evidence and mechanisms for the use of probiotics in the treatment of IBS.

  17. Brain gut microbiome interactions and functional bowel disorders

    Science.gov (United States)

    Alterations in the bidirectional interactions between the intestine and the nervous system have important roles in the pathogenesis of irritable bowel syndrome (IBS). A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. A small and poorly defined r...

  18. Interactions of AChE with Aβ Aggregates in Alzheimer’s Brain: Therapeutic Relevance of IDN 5706

    Directory of Open Access Journals (Sweden)

    Francisco Javier Carvajal

    2011-09-01

    Full Text Available Acetylcholinesterase (AChE; EC 3.1.1.7 plays a crucial role in the rapid hydrolysis of the neurotransmitter acetylcholine, in the central and peripheral nervous system and might also participate in non-cholinergic mechanism related to neurodegenerative diseases. Alzheimer’s disease (AD is a neurodegenerative disorder characterized by a progressive deterioration of cognitive abilities, amyloid-β peptide (Aβ accumulation and synaptic alterations. We have previously shown that AChE is able to accelerate the Aβ peptide assembly into Alzheimer-type aggregates increasing its neurotoxicity. Furthermore, AChE activity is altered in brain and blood of Alzheimer’s patients. The enzyme associated to amyloid plaques changes its enzymatic and pharmacological properties, as well as, increases its resistant to low pH, inhibitors and excess of substrate. Here, we reviewed the effects of IDN 5706, a hyperforin derivative that has potential preventive effects on the development of AD. Our results show that treatment with IDN5706 for 10 weeks increases brain AChE activity in seven month-old double transgenic mice (APPswe - PS1 and decreases the content of AChE associated with different types of amyloid plaques in this Alzheimer’s model. We concluded that early treatment with IDN 5706 decreases AChE-Aβ interaction and this effect might be of therapeutic interest in the treatment of AD.

  19. Anti-allergic role of cholinergic neuronal pathway via α7 nicotinic ACh receptors on mucosal mast cells in a murine food allergy model.

    Directory of Open Access Journals (Sweden)

    Takeshi Yamamoto

    Full Text Available The prevalence of food allergy (FA has increased in developed countries over the past few decades. However, no effective drug therapies are currently available. Therefore, we investigated cholinergic anti-inflammatory pathway as a regulatory system to ameliorate disrupted mucosal immune homeostasis in the gut based on the pathophysiological elucidation of mucosal mast cells (MMCs in a murine FA model. BALB/c mice sensitized with ovalbumin received repeated oral ovalbumin for the development of FA. FA mice developed severe allergic diarrhea and exhibited enhanced type 2 helper T (Th2 cell immune responses in both systemic immunity and mucosal immunity, along with MMCs hyperplasia in the colon. MMCs were localized primarily in the strategic position of the mucosal epithelium. Furthermore, the allergic symptoms did not develop in p85α disrupted phosphoinositide-3 kinase-deficient mice that lacked mast cells in the gut. Vagal stimulation by 2-deoxy-D-glucose and drug treatment with nicotinic ACh receptor (nAChR agonists (nicotine and α7 nAChR agonist GTS-21 alleviated the allergic symptoms in the FA mice. Nicotine treatment suppressed MMCs hyperplasia, enhanced MPO and upregulated mRNA expression of Th1 and Th2 cytokines in the FA mice colon. MMCs, which are negatively regulated by α7 nAChRs, were often located in close proximity to cholinergic CGRP-immunoreactive nerve fibers in the FA mice colon. The present results reveal that the cholinergic neuroimmune interaction via α7 nAChRs on MMCs is largely involved in maintaining intestinal immune homeostasis and can be a target for a new therapy against mucosal immune diseases with homeostatic disturbances such as FA.

  20. Acetylcholinesterase (AChE) gene modification in transgenic animals: functional consequences of selected exon and regulatory region deletion.

    Science.gov (United States)

    Camp, Shelley; Zhang, Limin; Marquez, Michael; de la Torre, Brian; Long, Jeffery M; Bucht, Goran; Taylor, Palmer

    2005-12-15

    AChE is an alternatively spliced gene. Exons 2, 3 and 4 are invariantly spliced, and this sequence is responsible for catalytic function. The 3' alternatively spliced exons, 5 and 6, are responsible for AChE disposition in tissue [J. Massoulie, The origin of the molecular diversity and functional anchoring of cholinesterases. Neurosignals 11 (3) (2002) 130-143; Y. Li, S. Camp, P. Taylor, Tissue-specific expression and alternative mRNA processing of the mammalian acetylcholinesterase gene. J. Biol. Chem. 268 (8) (1993) 5790-5797]. The splice to exon 5 produces the GPI anchored form of AChE found in the hematopoietic system, whereas the splice to exon 6 produces a sequence that binds to the structural subunits PRiMA and ColQ, producing AChE expression in brain and muscle. A third alternative RNA species is present that is not spliced at the 3' end; the intron 3' of exon 4 is used as coding sequence and produces the read-through, unanchored form of AChE. In order to further understand the role of alternative splicing in the expression of the AChE gene, we have used homologous recombination in stem cells to produce gene specific deletions in mice. Alternatively and together exon 5 and exon 6 were deleted. A cassette containing the neomycin gene flanked by loxP sites was used to replace the exon(s) of interest. Tissue analysis of mice with exon 5 deleted and the neomycin cassette retained showed very low levels of AChE expression, far less than would have been anticipated. Only the read-through species of the enzyme was produced; clearly the inclusion of the selection cassette disrupted splicing of exon 4 to exon 6. The selection cassette was then deleted in exon 5, exon 6 and exons 5 + 6 deleted mice by breeding to Ella-cre transgenic mice. AChE expression in serum, brain and muscle has been analyzed. Another AChE gene targeted mouse strain involving a region in the first intron, found to be critical for AChE expression in muscle cells [S. Camp, L. Zhang, M. Marquez, B

  1. Altered gastric emptying in patients with irritable bowel syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Caballero-Plasencia, A.M.; Valenzuela-Barranco, M. [Department of Medicine, School of Medicine, University of Granada (Spain); Herrerias-Gutierrez, J.M. [Division of Gastroenterology, University Hospital ``Virgen de la Macarena``, Sevilla (Spain); Esteban-Carretero, J.M. [Central Service of Investigation in Health Sciences, University of Cadiz, Cadiz (Spain)

    1999-04-29

    Irritable bowel syndrome is the most frequent functional disorder of the digestive system. Patients with irritable bowel syndrome have motor disorders not only in the colon, but also in other parts of the digestive tract such as the oesophagus and small intestine; however, it is not known whether the stomach is also involved. We used a radiolabelled mixed solid-liquid meal (technetium-99m for the solid component, indium-111 for the liquid component) to study gastric emptying of solids (GES), liquids (GEL) and indigestible solids (GER) in 50 patients diagnosed as having irritable bowel syndrome (30 with predominant constipation and 20 with predominant diarrhoea). GER was measured by counting the number of indigestible solids remaining in the stomach 4 h after they were swallowed. In patients with irritable bowel syndrome, GES and GEL were slower than in control subjects (P<0.05). GER was normal in all patients except for two women. Thirty-two patients (64%) showed delayed GES, 29 (58%) delayed GEL, and 2 (4%) delayed GER. Among patients with irritable bowel syndrome, GES was slower in those with predominant constipation than in those with predominant diarrhoea (P<0.05); GEL and GER were similar in both groups. Gastroparesis was found in a large proportion of patients with irritable bowel syndrome, suggesting the presence of a more generalised motor disorder of the gut. (orig.) With 1 fig., 3 tabs., 48 refs.

  2. [Study on treatment of irritable bowel syndrome: based on relationship between heart and intestines].

    Science.gov (United States)

    Wang, Su-Na; Wang, Zu-Hong; Xie, Su-Juan; Han, Li-Bing; Yi, Rong

    2010-11-01

    The article puts forward the treatment of irritable bowel syndrome through regulating heart vitality since it is held that the pathological factors of the disease lay in dysfunction of heart and intestines as well as disorder of qi circulation. At the same time, the internal-external relationship between the heart the small intestine is discussed from the theory of Brain-gut Axis in modern medicine, which provides theoretical base of modern medicine for the treatment of irritable bowel syndrome through regulation of the heart functions.

  3. Immunomodulation of enteric neural function in irritable bowel syndrome

    OpenAIRE

    O’Malley, Dervla

    2015-01-01

    Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder which is characterised by symptoms such as bloating, altered bowel habit and visceral pain. It’s generally accepted that miscommunication between the brain and gut underlies the changes in motility, absorpto-secretory function and pain sensitivity associated with IBS. However, partly due to the lack of disease-defining biomarkers, understanding the aetiology of this complex and multifactorial disease remains elusi...

  4. Assessing the reactivation efficacy of hydroxylamine anion towards VX-inhibited AChE: a computational study.

    Science.gov (United States)

    Khan, Md Abdul Shafeeuulla; Ganguly, Bishwajit

    2012-05-01

    Oximate anions are used as potential reactivating agents for OP-inhibited AChE because of they possess enhanced nucleophilic reactivity due to the α-effect. We have demonstrated the process of reactivating the VX-AChE adduct with formoximate and hydroxylamine anions by applying the DFT approach at the B3LYP/6-311 G(d,p) level of theory. The calculated results suggest that the hydroxylamine anion is more efficient than the formoximate anion at reactivating VX-inhibited AChE. The reaction of formoximate anion and the VX-AChE adduct is a three-step process, while the reaction of hydroxylamine anion with the VX-AChE adduct seems to be a two-step process. The rate-determining step in the process is the initial attack on the VX of the VX-AChE adduct by the nucleophile. The subsequent steps are exergonic in nature. The potential energy surface (PES) for the reaction of the VX-AChE adduct with hydroxylamine anion reveals that the reactivation process is facilitated by the lower free energy of activation (by a factor of 1.7 kcal mol(-1)) than that of the formoximate anion at the B3LYP/6-311 G(d,p) level of theory. The higher free energy of activation for the reverse reactivation reaction between hydroxylamine anion and the VX-serine adduct further suggests that the hydroxylamine anion is a very good antidote agent for the reactivation process. The activation barriers calculated in solvent using the polarizable continuum model (PCM) for the reactivation of the VX-AChE adduct with hydroxylamine anion were also found to be low. The calculated results suggest that V-series compounds can be more toxic than G-series compounds, which is in accord with earlier experimental observations.

  5. Healthy human gut phageome.

    Science.gov (United States)

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T; van der Oost, John; de Vos, Willem M; Young, Mark J

    2016-09-13

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of humans, we analyzed a deep DNA sequence dataset of active bacteriophages and available metagenomic datasets of the gut bacteriophage community from healthy individuals. We found 23 shared bacteriophages in more than one-half of 64 healthy individuals from around the world. These shared bacteriophages were found in a significantly smaller percentage of individuals with gastrointestinal/irritable bowel disease. A network analysis identified 44 bacteriophage groups of which 9 (20%) were shared in more than one-half of all 64 individuals. These results provide strong evidence of a healthy gut phageome (HGP) in humans. The bacteriophage community in the human gut is a mixture of three classes: a set of core bacteriophages shared among more than one-half of all people, a common set of bacteriophages found in 20-50% of individuals, and a set of bacteriophages that are either rarely shared or unique to a person. We propose that the core and common bacteriophage communities are globally distributed and comprise the HGP, which plays an important role in maintaining gut microbiome structure/function and thereby contributes significantly to human health.

  6. Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome

    OpenAIRE

    Sagami, Y; Shimada, Y; Tayama, J; Nomura, T; Satake, M; Endo, Y; Shoji, T; Karahashi, K; Hongo, M; Fukudo, S

    2004-01-01

    Background and aims: Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of α-helical CRH (αhCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patient...

  7. Hypnotherapy for children with functional abdominal pain or irritable bowel syndrome: a randomized controlled trial

    NARCIS (Netherlands)

    Vlieger, Arine M.; Menko-Frankenhuis, Carla; Wolfkamp, Simone C. S.; Tromp, Ellen; Benninga, Marc A.

    2007-01-01

    BACKGROUND & AIMS: Functional abdominal pain (FAP) and irritable bowel syndrome (IBS) are highly prevalent in childhood. A substantial proportion of patients continues to experience long-lasting symptoms. Gut-directed hypnotherapy (HT) has been shown to be highly effective in the treatment of adult

  8. A molecular analysis of fecal and mucosal bacterial communities in irritable bowel syndrome.

    LENUS (Irish Health Repository)

    Codling, Caroline

    2010-02-01

    The objectives of this study were, firstly, to determine the diversity of the host\\'s gut microbiota in irritable bowel syndrome (IBS) using a culture-independent method (DGGE of the 16S rRNA gene) and, secondly, to examine mucosal biopsies of IBS patients and compare them to their own fecal microbiota.

  9. Toxicological and biochemical characterizations of AChE in phosalone-susceptible and resistant populations of the common pistachio psyllid, Agonoscena pistaciae

    Science.gov (United States)

    Alizadeh, Ali; Talebi-Jahromi, Khalil; Hosseininaveh, Vahid; Ghadamyari, Mohammad

    2014-01-01

    Abstract The toxicological and biochemical characteristics of acetylcholinesterases (AChE) in nine populations of the common pistachio psyllid, Agonoscena pistaciae Burckhardt and Lauterer (Hemiptera: Psyllidae), were investigated in Kerman Province, Iran. Nine A. pistaciae populations were collected from pistachio orchards, Pistacia vera L. (Sapindales: Anacardiaceae), located in Rafsanjan, Anar, Bam, Kerman, Shahrbabak, Herat, Sirjan, Pariz, and Paghaleh regions of Kerman province. The previous bioassay results showed these populations were susceptible or resistant to phosalone, and the Rafsanjan population was most resistant, with a resistance ratio of 11.3. The specific activity of AChE in the Rafsanjan population was significantly higher than in the susceptible population (Bam). The affinity ( KM ) and hydrolyzing efficiency ( Vmax ) of AChE on acetylthiocholine iodide, butyrylthiocholine iodide, and propionylthiocholine odide as artificial substrates were clearly lower in the Bam population than that in the Rafsanjan population. These results indicated that the AChE of the Rafsanjan population had lower affinity to these substrates than that of the susceptible population. The higher Vmax value in the Rafsanjan population compared to the susceptible population suggests a possible over expression of AChE in the Rafsanjan population. The in vitro inhibitory effect of several organophosphates and carbamates on AChE of the Rafsanjan and Bam populations was determined. Based on I50, the results showed that the ratios of AChE insensitivity of the resistant to susceptible populations were 23 and 21.7-fold to monocrotophos and phosphamidon, respectively. Whereas, the insensitivity ratios for Rafsanjan population were 0.86, 0.8, 0.78, 0.46, and 0.43 for carbaryl, eserine, propoxur, m-tolyl methyl carbamate, and carbofuran, respectively, suggesting negatively correlated sensitivity to organophosphate-insensitive AChE. Therefore, AChE from the Rafsanjan population showed

  10. Gut-directed hypnotherapy for functional abdominal pain or irritable bowel syndrome in children: a systematic review.

    Science.gov (United States)

    Rutten, Juliette M T M; Reitsma, Johannes B; Vlieger, Arine M; Benninga, Marc A

    2013-04-01

    Gut directed hypnotherapy (HT) is shown to be effective in adult functional abdominal pain (FAP) and irritable bowel syndrome (IBS) patients. We performed a systematic review to assess efficacy of HT in paediatric FAP/IBS patients. We searched Medline, Embase, PsychINFO, Cumulative Index to Nursing and Allied Health Literature databases and Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) in children with FAP or IBS, investigating efficacy of HT on the following outcomes: abdominal pain scores, quality of life, costs and school absenteeism. Three RCT comparing HT to a control treatment were included with sample sizes ranging from 22 to 52 children. We refrained from statistical pooling because of low number of studies and many differences in design and outcomes. Two studies examined HT performed by a therapist, one examined HT through self-exercises on audio CD. All trials showed statistically significantly greater improvement in abdominal pain scores among children receiving HT. One trial reported beneficial effects sustained after 1 year of follow-up. One trial reported statistically significant improvement in quality of life in the HT group. Two trials reported significant reductions in school absenteeism after HT. Therapeutic effects of HT seem superior to standard medical care in children with FAP or IBS. It remains difficult to quantify exact benefits. The need for more high quality research is evident.

  11. Stress and visceral pain: focusing on irritable bowel syndrome.

    Science.gov (United States)

    Fukudo, Shin

    2013-12-01

    Recent advances in brain science have shown that the brain function encoding emotion depends on interoceptive signals such as visceral pain. Visceral pain arose early in our evolutionary history. Bottom-up processing from gut-to-brain and top-down autonomic/neuroendocrine mechanisms in brain-to-gut signaling constitute a circuit. Brain imaging techniques have enabled us to depict the visceral pain pathway as well as the related emotional circuit. Irritable bowel syndrome (IBS) is characterized by chronic recurrent abdominal pain or abdominal discomfort associated with bowel dysfunction. It is also thought to be a disorder of the brain-gut link associated with an exaggerated response to stress. Corticotropin-releasing hormone (CRH), a major mediator of the stress response in the brain-gut axis, is an obvious candidate in the pathophysiology of IBS. Indeed, administration of CRH has been shown to aggravate the visceral sensorimotor response in IBS patients, and the administration of peptidergic CRH antagonists seems to alleviate IBS pathophysiology. Serotonin (5-HT) is another likely candidate associated with brain-gut function in IBS, as 5-HT3 antagonists, 5-HT4 agonists, and antidepressants were demonstrated to regulate 5-HT neurotransmission in IBS patients. Autonomic nervous system function, the neuroimmune axis, and the brain-gut-microbiota axis show specific profiles in IBS patients. Further studies on stress and visceral pain neuropathways in IBS patients are warranted. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  12. Stem Cells in the Intestine: Possible Roles in Pathogenesis of Irritable Bowel Syndrome.

    Science.gov (United States)

    Ratanasirintrawoot, Sutheera; Israsena, Nipan

    2016-07-30

    Irritable bowel syndrome is one of the most common functional gastrointestinal (GI) disorders that significantly impair quality of life in patients. Current available treatments are still not effective and the pathophysiology of this condition remains unclearly defined. Recently, research on intestinal stem cells has greatly advanced our understanding of various GI disorders. Alterations in conserved stem cell regulatory pathways such as Notch, Wnt, and bone morphogenic protein/TGF- β have been well documented in diseases such as inflammatory bowel diseases and cancer. Interaction between intestinal stem cells and various signals from their environment is important for the control of stem cell self-renewal, regulation of number and function of specific intestinal cell types, and maintenance of the mucosal barrier. Besides their roles in stem cell regulation, these signals are also known to have potent effects on immune cells, enteric nervous system and secretory cells in the gut, and may be responsible for various aspects of pathogenesis of functional GI disorders, including visceral hypersensitivity, altered gut motility and low grade gut inflammation. In this article, we briefly summarize the components of these signaling pathways, how they can be modified by extrinsic factors and novel treatments, and provide evidenced support of their roles in the inflammation processes. Furthermore, we propose how changes in these signals may contribute to the symptom development and pathogenesis of irritable bowel syndrome.

  13. Novel bis-(−)-nor-meptazinol derivatives act as dual binding site AChE inhibitors with metal-complexing property

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Wei [Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 200032 (China); NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, 2140 Xietu Road, Shanghai 200032 (China); Li, Juan [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); Qiu, Zhuibai [Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 200032 (China); Xia, Zheng [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); Li, Wei [Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 200032 (China); Yu, Lining; Chen, Hailin; Chen, Jianxing [NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, 2140 Xietu Road, Shanghai 200032 (China); Chen, Yan; Hu, Zhuqin; Zhou, Wei; Shao, Biyun; Cui, Yongyao [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); Xie, Qiong, E-mail: xiejoanxq@gmail.com [Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 200032 (China); Chen, Hongzhuan, E-mail: yaoli@shsmu.edu.cn [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China)

    2012-10-01

    The strategy of dual binding site acetylcholinesterase (AChE) inhibition along with metal chelation may represent a promising direction for multi-targeted interventions in the pathophysiological processes of Alzheimer's disease (AD). In the present study, two derivatives (ZLA and ZLB) of a potent dual binding site AChE inhibitor bis-(−)-nor-meptazinol (bis-MEP) were designed and synthesized by introducing metal chelating pharmacophores into the middle chain of bis-MEP. They could inhibit human AChE activity with IC{sub 50} values of 9.63 μM (for ZLA) and 8.64 μM (for ZLB), and prevent AChE-induced amyloid-β (Aβ) aggregation with IC{sub 50} values of 49.1 μM (for ZLA) and 55.3 μM (for ZLB). In parallel, molecular docking analysis showed that they are capable of interacting with both the catalytic and peripheral anionic sites of AChE. Furthermore, they exhibited abilities to complex metal ions such as Cu(II) and Zn(II), and inhibit Aβ aggregation triggered by these metals. Collectively, these results suggest that ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency, and may be potential leads of value for further study on disease-modifying treatment of AD. -- Highlights: ► Two novel bis-(−)-nor-meptazinol derivatives are designed and synthesized. ► ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency. ► They are potential leads for disease-modifying treatment of Alzheimer's disease.

  14. Novel bis-(−)-nor-meptazinol derivatives act as dual binding site AChE inhibitors with metal-complexing property

    International Nuclear Information System (INIS)

    Zheng, Wei; Li, Juan; Qiu, Zhuibai; Xia, Zheng; Li, Wei; Yu, Lining; Chen, Hailin; Chen, Jianxing; Chen, Yan; Hu, Zhuqin; Zhou, Wei; Shao, Biyun; Cui, Yongyao; Xie, Qiong; Chen, Hongzhuan

    2012-01-01

    The strategy of dual binding site acetylcholinesterase (AChE) inhibition along with metal chelation may represent a promising direction for multi-targeted interventions in the pathophysiological processes of Alzheimer's disease (AD). In the present study, two derivatives (ZLA and ZLB) of a potent dual binding site AChE inhibitor bis-(−)-nor-meptazinol (bis-MEP) were designed and synthesized by introducing metal chelating pharmacophores into the middle chain of bis-MEP. They could inhibit human AChE activity with IC 50 values of 9.63 μM (for ZLA) and 8.64 μM (for ZLB), and prevent AChE-induced amyloid-β (Aβ) aggregation with IC 50 values of 49.1 μM (for ZLA) and 55.3 μM (for ZLB). In parallel, molecular docking analysis showed that they are capable of interacting with both the catalytic and peripheral anionic sites of AChE. Furthermore, they exhibited abilities to complex metal ions such as Cu(II) and Zn(II), and inhibit Aβ aggregation triggered by these metals. Collectively, these results suggest that ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency, and may be potential leads of value for further study on disease-modifying treatment of AD. -- Highlights: ► Two novel bis-(−)-nor-meptazinol derivatives are designed and synthesized. ► ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency. ► They are potential leads for disease-modifying treatment of Alzheimer's disease.

  15. Psyllium fiber reduces abdominal pain in children with irritable bowel syndrome in a randomized, double-blind trial

    Science.gov (United States)

    We sought to determine the efficacy of psyllium fiber treatment on abdominal pain and stool patterns in children with irritable bowel syndrome (IBS). We evaluated effects on breath hydrogen and methane production, gut permeability, and microbiome composition. We also investigated whether psychologic...

  16. Neurobiology of Depression and Irritable Bowel Syndrome Comorbidity

    Directory of Open Access Journals (Sweden)

    Ozlem Donat Eker

    2009-08-01

    Full Text Available Irritable bowel syndrome is a disabling functional disorder with a frequent comorbidity of depression though underlying mechanisms remain yet little understood. Various signs and symptoms have been determined as diagnostic criteria in recent years and standardized as Rome-III criteria. Irritable bowel syndrome can have constipation-dominant, diarrhea-dominant or mixed clinical presentations. Main features can be summarized as continuous and recurrent abdominal pain or discomfort associated with a change of stool frequency or consistency and usually relief of symptoms with defe-cation in the absence of physical or laboratory abnormalities indicative of an organic etiology. The frequency of major depressive disorder diagnosis reaches up to two thirds of irritable bowel syndrome patients. Moreover, the comorbidity of irritable bowel syndrome among patients with major depression is highly frequent (30%. The mechanism underlying irritable bowel syndrome which have been considered as a kind of a somatization disorder for a long time and now as a functional bowel disease is in the brain-gut axis. Low grade mucosal inflammation and cytokines originating from mucosal inflammation have important functions in the pathophysiology of irritable bowel syndrome and its comorbidity with major depression. Besides the inflammatory factors lumbosacral visceral hyperexcitability which is an individual variation is proposed as the main underlying cause of irritable bowel syndrome. Visceral hyper-excitability is mediated by cytokines and neuro-mediators and stress is known to increase the effect of this mechanism. Furthermore, molecules participating in this mechanism (e.g. cytokines, corticotrophin releasing factor, neurokinins and monoamines play important roles in the pathophysiology of depression. Increased activation in the pain matrix (thalamus – insula – prefrontal cortex and insufficiency of endogenous pain inhibitory system are regarded as possible

  17. Evaluation of the Toxicity, AChE Activity and DNA Damage Caused by Imidacloprid on Earthworms, Eisenia fetida.

    Science.gov (United States)

    Wang, Kai; Qi, Suzhen; Mu, Xiyan; Chai, Tingting; Yang, Yang; Wang, Dandan; Li, Dongzhi; Che, Wunan; Wang, Chengju

    2015-10-01

    Imidacloprid is a well-known pesticide and it is timely to evaluate its toxicity to earthworms (Eisenia fetida). In the present study, the effect of imidacloprid on reproduction, growth, acetylcholinesterase (AChE) and DNA damage in earthworms was assessed using an artificial soil medium. The median lethal concentration (LC50) and the median number of hatched cocoons (EC50) of imidacloprid to earthworms was 3.05 and 0.92 mg/kg respectively, the lowest observed effect concentration of imidacloprid about hatchability, growth, AChE activity and DNA damage was 0.02, 0.5, 0.1 and 0.5 mg/kg, respectively.

  18. THE ROLES OF DETOXIFYING ENZYMES AND AChE INSENSITIVITY IN METHAMIDOPHOS RESISTANCE DEVELOPMENT AND DECLINE IN NILAPARVATA LUGENS

    Institute of Scientific and Technical Information of China (English)

    Ze-wenLiu; Zhao-junHan; Ling-chunZhang

    2003-01-01

    Methamidophos resistance of brown planthopper (Nilaparvata lugens Stal, BPH) was selected in laboratory. After successive selection for 9 generations, the selection was ceased by rearing BPH without contact with any insecticide for 9 generations. In the full course, the successive changes of esterase activity, MFO activity, GSTs activity and AChE insensitivity were analyzed. The results showed that the change of esterase activity was high correlated with that of methamidophos in the full course, which indicated that esterase played very important role both in the resistance development and in the resistance decline. However, the change of AChE insensitivity only significantly correlated with that of resistance in the development stage, and the change of MFO activity or GSTs activity only significantly correlated with that of the resistance in the decline stage, which indicated the changes of AChE insensitivity, MFO activity or GSTs activity only played some roles in different stages of the resistance change.

  19. The Role of AChE in Swimming Behavior of Daphnia magna: Correlation Analysis of Both Parameters Affected by Deltamethrin and Methomyl Exposure

    Directory of Open Access Journals (Sweden)

    Qing Ren

    2017-01-01

    Full Text Available The unpredictable toxicity of insecticides may cause behavior disorder of biological organisms. In order to assess the role of acetylcholinesterase (AChE in swimming behavior of Daphnia magna, a correlation analysis of both parameters in 24 h exposure of deltamethrin (DM and methomyl (MT was investigated. The behavior responses of D. magna in DM (13.36 μg/L and 33.40 μg/L and MT (19.66 μg/L and 49.15 μg/L suggested that recovery behavior in the adjustment phase was crucial, and behavior homeostasis provided them with an optimal way to achieve a wider tolerance against environmental stress. During the experiment, positive effects on AChE activity occurred in the beginning of the exposure. Even though the de novo synthesis of AChE in D. magna might help it recover, the AChE inhibition in different treatments could be observed. Some induction effects on AChE activity at the beginning of exposure occurred, and a 50% decrease may cause toxic effects on behavior. In most treatments, the results showed that both behavior strength and AChE activity stayed in the same field within a correlation circle. These results illustrated that the environmental stress caused by both DM and MT could inhibit AChE activity and subsequently induce a stepwise behavior response, though both pesticides affect it as direct and indirect inhibitors, respectively.

  20. Long-term follow-up of gut-directed hypnotherapy vs. standard care in children with functional abdominal pain or irritable bowel syndrome.

    Science.gov (United States)

    Vlieger, Arine M; Rutten, Juliette M T M; Govers, Anita M A P; Frankenhuis, Carla; Benninga, Marc A

    2012-04-01

    We previously showed that gut-directed hypnotherapy (HT) is highly effective in the treatment of children with functional abdominal pain (FAP) and irritable bowel syndrome (IBS). Aim of this follow-up study was to investigate the long-term effects of HT vs. standard medical treatment plus supportive therapy (SMT). All 52 participants of our previous randomized controlled trial (RCT) were invited to complete a standardized abdominal pain diary, on which pain frequency and pain intensity were scored. Furthermore, the Children's Somatization Inventory (CSI) and a general quality of life (QOL) questionnaire were filled out. Clinical remission was defined as > 80% improvement in pain scores compared with baseline. All 27 HT patients and 22 out of 25 SMT patients participated in this study. Two patients of the SMT group were lost to follow-up and one refused to participate. After a mean duration of 4.8 years follow-up (3.4-6.7), HT was still highly superior to conventional therapy with 68 vs. 20% of the patients in remission after treatment (P = 0.005). Pain intensity and pain frequency scores at follow-up were 2.8 and 2.3, respectively, in the HT group compared with 7.3 and 7.1 in the SMT group (P < 0.01). Also, somatization scores were lower in the HT group (15.2 vs. 22.8; P = 0.04). No differences were found in QOL, doctors' visits, and missed days of school or work between the two groups. The beneficial effects of gut-directed HT are long lasting in children with FAP or IBS with two thirds still in remission almost 5 years after treatment, making it a highly valuable therapeutic option.

  1. Selenofuranoside Ameliorates Memory Loss in Alzheimer-Like Sporadic Dementia: AChE Activity, Oxidative Stress, and Inflammation Involvement

    Directory of Open Access Journals (Sweden)

    Cristiano Chiapinotto Spiazzi

    2015-01-01

    Full Text Available Alzheimer’s disease (AD is becoming more common due to the increase in life expectancy. This study evaluated the effect of selenofuranoside (Se in an Alzheimer-like sporadic dementia animal model. Male mice were divided into 4 groups: control, Aβ, Se, and Aβ + Se. Single administration of Aβ peptide (fragments 25–35; 3 nmol/3 μL or distilled water was administered via intracerebroventricular (i.c.v. injection. Selenofuranoside (5 mg/kg or vehicle (canola oil was administered orally 30 min before Aβ and for 7 subsequent days. Memory was tested through the Morris water maze (MWM and step-down passive-avoidance (SDPA tests. Antioxidant defenses along with reactive species (RS were assessed. Inflammatory cytokines levels and AChE activity were measured. SOD activity was inhibited in the Aβ group whereas RS were increased. AChE activity, GSH, and IL-6 levels were increased in the Aβ group. These changes were reflected in impaired cognition and memory loss, observed in both behavioral tests. Se compound was able to protect against memory loss in mice in both behavioral tests. SOD and AChE activities as well as RS and IL-6 levels were also protected by Se administration. Therefore, Se is promising for further studies.

  2. Anti-irritants II: Efficacy against cumulative irritation

    DEFF Research Database (Denmark)

    Andersen, Flemming; Hedegaard, Kathryn; Petersen, Thomas Kongstad

    2006-01-01

    window of opportunity in which to demonstrate efficacy. Therefore, the effect of AI was studied in a cumulative irritation model by inducing irritant dermatitis with 10 min daily exposures for 5+4 days (no irritation on weekend) to 1% sodium lauryl sulfate on the right and 20% nonanoic acid on the left...

  3. Convergence of neuro-endocrine-immune pathways in the pathophysiology of irritable bowel syndrome

    OpenAIRE

    Buckley, Maria M; O’Mahony, Siobhain M; O’Malley, Dervla

    2014-01-01

    Disordered signalling between the brain and the gut are generally accepted to underlie the functional bowel disorder, irritable bowel syndrome (IBS). However, partly due to the lack of disease-defining biomarkers, understanding the aetiology of this complex and multifactorial disease remains elusive. This common gastrointestinal disorder is characterised by alterations in bowel habit such as diarrhoea and/or constipation, bloating and abdominal pain, and symptom exacerbation has been linked w...

  4. Design, synthesis and evaluation of some N-methylenebenzenamine derivatives as selective acetylcholinesterase (AChE) inhibitor and antioxidant to enhance learning and memory.

    Science.gov (United States)

    Shrivastava, Sushant K; Srivastava, Pavan; Upendra, T V R; Tripathi, Prabhash Nath; Sinha, Saurabh K

    2017-02-15

    Series of some 3,5-dimethoxy-N-methylenebenzenamine and 4-(methyleneamino)benzoic acid derivatives comprising of N-methylenebenzenamine nucleus were designed, synthesized, characterized, and assessed for their acetylcholinesterase (AChE), butyrylcholinesterase (BChE) inhibitory, and antioxidant activity thereby improving learning and memory in rats. The IC 50 values of all the compound along with standard were determined on AChE and BChE enzyme. The free radical scavenging activity was also assessed by in vitro DPPH (2,2-diphenyl-1-picryl-hydrazyl) and hydrogen peroxide radical scavenging assay. The selective inhibitions of all compounds were observed against AChE in comparison with standard donepezil. The enzyme kinetic study of the most active compound 4 indicated uncompetitive AChE inhibition. The docking studies of compound 4 exhibited the worthy interaction on active-site gorge residues Phe330 and Trp279 responsible for its high affinity towards AChE, whereas lacking of the BChE inhibition was observed due to a wider gorge binding site and absence of important aromatic amino acids interactions. The ex vivo study confirmed AChE inhibition abilities of compound 4 at brain site. Further, a considerable decrease in escape latency period of the compound was observed in comparison with standard donepezil through in vivo Spatial Reference Memory (SRM) and Spatial Working Memory (SWM) models which showed the cognition-enhancing potential of compound 4. The in vivo reduced glutathione (GSH) estimation on rat brain tissue homogenate was also performed to evaluate free radical scavenging activity substantiated the antioxidant activity in learning and memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. [Irritable bowel syndrome: New pathophysiological hypotheses and practical issues].

    Science.gov (United States)

    Duboc, H; Dior, M; Coffin, B

    2016-08-01

    In 2015, besides the fact that it still fills the gastroenterologists' offices and impairs patient's quality of life, the irritable bowel syndrome has considerably evolved on several points. The pathophysiology is now organized around a consensual hypothesis called the "brain-gut axis", which gather all the influences of peripheral factors as gut microbiota or local serotonin secretion, on the central pain perception, contributing to visceral hypersensitivity and transit modifications. About the diagnosis, the key message is "avoid over-prescription" of additional tests, and reminds that a positive clinical diagnosis based on Rome III criteria is possible after the elimination of simple clinical warning signs. Finally, the food component, a neglected and historical claim of patients, finally finds a strong scientific rational, with a diet low in fermentable sugar and polyols, that gives positive and reproducible results. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  6. The Place of Stress and Emotions in the Irritable Bowel Syndrome.

    Science.gov (United States)

    Pellissier, S; Bonaz, B

    2017-01-01

    Our emotional state can have many consequences on our somatic health and well-being. Negative emotions such as anxiety play a major role in gut functioning due to the bidirectional communications between gut and brain, namely, the brain-gut axis. The irritable bowel syndrome (IBS), characterized by an unusual visceral hypersensitivity, is the most common disorder encountered by gastroenterologists. Among the main symptoms, the presence of current or recurrent abdominal pain or discomfort associated with bloating and altered bowel habits characterizes this syndrome that could strongly alter the quality of life. This chapter will present the physiopathology of IBS and explain how stress influences gastrointestinal functions (permeability, motility, microbiota, sensitivity, secretion) and how it could be predominantly involved in IBS. This chapter will also describe the role of the autonomic nervous system and the hypothalamic-pituitary axis through vagal tone and cortisol homeostasis. An analysis is made about how emotions and feelings are involved in the disruption of homeostasis, and we will see to what extent the balance between vagal tone and cortisol may reflect dysfunctions of the brain-gut homeostasis. Finally, the interest of therapeutic treatments focused on stress reduction and vagal tone enforcement is discussed. © 2017 Elsevier Inc. All rights reserved.

  7. 大白鼠海马神经元NOS与AChE活性的研究%Study on the NOS and AChE Activity in the Hippocampus Neurons of Rat

    Institute of Scientific and Technical Information of China (English)

    夏保芦; 杨荣; 杨友华; 杨敏; 黄丹

    2005-01-01

    目的:观察大白鼠海马不同亚区一氧化氮合酶(NOS)与乙酰胆碱酯酶(AChE)阳性神经元的活性.方法:分别采用还原型尼克酰胺嘌呤二核苷酸脱氢酶(NADPH-d)和乙酰胆碱酯酶(AChE)组织化学方法对大白鼠海马不同亚区NOS和AChE阳性神经元的分布以及活性进行研究.结果:海马不同亚区均含有NOS和AChE阳性神经元,其中CA2区NOS呈强阳性反应,CA3区AChE呈强阳性反应.结论:实验表明,NOS和AChE阳性神经元广泛分布于大白鼠海马不同亚区,为进一步探讨海马的学习记忆功能机制提供了形态学佐证.

  8. Are You a Gut Responder? Hints on Coping with an Irritable Bowel

    Science.gov (United States)

    ... problems to contend with. These can interfere with work or school and social functions both in obvious and subtle ways – including ... a better understanding of your own gut-brain connections, ask your doctor to suggest a mental health ... Read More Personal Relationships ...

  9. Anti-irritants I: Dose-response in acute irritation

    DEFF Research Database (Denmark)

    Andersen, Flemming; Hedegaard, Kathryn; Petersen, Thomas Kongstad

    2006-01-01

    acute irritation in healthy volunteers. Each AI was used in 3 concentrations. Acute irritation was induced by occlusive tests with 1% sodium lauryl sulfate and 20% nonanoic acid in N-propanol. The irritant reactions were treated twice daily with AI-containing formulations from the time of removal...

  10. Gut microbiota in health and disease

    Directory of Open Access Journals (Sweden)

    M.E. Icaza-Chávez

    2013-10-01

    Full Text Available Gut microbiota is the community of live microorganisms residing in the digestive tract. There are many groups of researchers worldwide that are working at deciphering the collective genome of the human microbiota. Modern techniques for studying the microbiota have made us aware of an important number of nonculturable bacteria and of the relation between the microorganisms that live inside us and our homeostasis. The microbiota is essential for correct body growth, the development of immunity, and nutrition. Certain epidemics affecting humanity such as asthma and obesity may possibly be explained, at least partially, by alterations in the microbiota. Dysbiosis has been associated with a series of gastrointestinal disorders that include non-alcoholic fatty liver disease, celiac disease, and irritable bowel syndrome. The present article deals with the nomenclature, modern study techniques, and functions of gut microbiota, and its relation to health and disease.

  11. Effects of EGCG and Chlorpyrifos on the Mortality, AChE and GSH of Adult Zebrafish: Independent and Combination

    Science.gov (United States)

    Zhang, Rong; Zhang, Jian; Gao, Qian; Guo, Nichun

    2018-01-01

    Chlorpyrifos is a neurotoxic agent and also causes oxidative stress in the body. EGCG is a typical strong antioxidant and has been reported to be neuroprotective. Our study investigated the mortality, the activity of acetylcholinesterase (AChE) in the brain and glutathione (GSH) in the liver of the adult Zebrafish in present of Chlorpyrifos and EGCG independent and combination. The results indicated that after the addition of EGCG, the mortality of zebrafish induced by Chlorpyrifos was reduced and the activity of AChE and glutathione (GSH) inhibited by Chlorpyrifos in zebrafish was significantly increased, which demonstrated that EGCG inhibited the toxicity Chlorpyrifos to zebrafish. The inhibition was dependent on the concentration of EGCG and Chlorpyrifos, which was not shown a gradual change trend but a complex situation.

  12. The human gut microbiome and its dysfunctions through the meta-omics prism.

    Science.gov (United States)

    Mondot, Stanislas; Lepage, Patricia

    2016-05-01

    The microorganisms inhabiting the human gut are abundant (10(14) cells) and diverse (approximately 500 species per individual). It is now acknowledged that the microbiota has coevolved with its host to achieve a symbiotic relationship, leading to physiological homeostasis. The gut microbiota ensures vital functions, such as food digestibility, maturation of the host immune system, and protection against pathogens. Over the last few decades, the gut microbiota has also been associated with numerous diseases, such as inflammatory bowel disease, irritable bowel syndrome, obesity, and metabolic diseases. In most of these pathologies, a microbial dysbiosis has been found, indicating shifts in the taxonomic composition of the gut microbiota and changes in its functionality. Our understanding of the influence of the gut microbiota on human health is still growing. Working with microorganisms residing in the gut is challenging since most of them are anaerobic and a vast majority (approximately 75%) are uncultivable to date. Recently, a wide range of new approaches (meta-omics) has been developed to bypass the uncultivability and reveal the intricate mechanisms that sustain gut microbial homeostasis. After a brief description of these approaches (metagenomics, metatranscriptomics, metaproteomics, and metabolomics), this review will discuss the importance of considering the gut microbiome as a structured ecosystem and the use of meta-omics to decipher dysfunctions of the gut microbiome in diseases. © 2016 New York Academy of Sciences.

  13. Common SAR Derived from Linear and Non-linear QSAR Studies on AChE Inhibitors used in the Treatment of Alzheimer's Disease.

    Science.gov (United States)

    Pulikkal, Babitha Pallikkara; Marunnan, Sahila Mohammed; Bandaru, Srinivas; Yadav, Mukesh; Nayarisseri, Anuraj; Sureshkumar, Sivanpillai

    2017-11-14

    Deficits in cholinergic neurotransmission due to the degeneration of cholinergic neurons in the brain are believed to be one of the major causes of the memory impairments associated with AD. Targeting acetyl cholinesterase (AChE) surfaced as a potential therapeutic target in the treatment of Alzheimer's disease. The present study is pursued to develop quantitative structure activity relationship (QSAR) models to determine chemical descriptors responsible for AChE activity. Two different sets of AChE inhibitors, dataset-I (30 compounds) and dataset-II (20 compounds) were investigated through MLR aided linear and SVM aided non-linear QSAR models. The obtained QSAR models were found statistically fit, stable and predictive on validation scales. These QSAR models were further investigated for their common structure-activity relationship in terms of overlapping molecular descriptors selection. Atomic mass weighted 3D Morse descriptors (MATS5m) and Radial Distribution Function (RDF045m) descriptors were found in common SAR for both the datasets. Electronegativity weighted (MATS5e, HATSe, and Mor17e) descriptors have also been identified in regulative roles towards endpoint values of dataset-I and dataset-II. The common SAR identified in these linear and non-linear QSAR models could be utilized to design novel inhibitors of AChE with improved biological activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Randomised clinical trial: the efficacy of gut-directed hypnotherapy is similar to that of the low FODMAP diet for the treatment of irritable bowel syndrome.

    Science.gov (United States)

    Peters, S L; Yao, C K; Philpott, H; Yelland, G W; Muir, J G; Gibson, P R

    2016-09-01

    A low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet is effective in treating irritable bowel syndrome (IBS). To compare the effects of gut-directed hypnotherapy to the low FODMAP diet on gastrointestinal symptoms and psychological indices, and assess additive effects. Irritable bowel syndrome patients were randomised (computer-generated list), to receive hypnotherapy, diet or a combination. Primary end-point: change in overall gastrointestinal symptoms across the three groups from baseline to week 6. Secondary end-points: changes in psychological indices, and the durability of effects over 6 months. Of 74 participants, 25 received hypnotherapy, 24 diet and 25 combination. There were no demographic differences at baseline across groups. Improvements in overall symptoms were observed from baseline to week 6 for hypnotherapy [mean difference (95% CI): -33 (-41 to -25)], diet [-30 (-42 to -19)] and combination [-36 (-45 to -27)] with no difference across groups (P = 0.67). This represented ≥20 mm improvement on visual analogue scale in 72%, 71% and 72%, respectively. This improvement relative to baseline symptoms was maintained 6 months post-treatment in 74%, 82% and 54%. Individual gastrointestinal symptoms similarly improved. Hypnotherapy resulted in superior improvements on psychological indices with mean change from baseline to 6 months in State Trait Personality Inventory trait anxiety of -4(95% CI -6 to -2) P hypnotherapy are similar to those of the low FODMAP diet for relief of gastrointestinal symptoms. Hypnotherapy has superior efficacy to the diet on psychological indices. No additive effects were observed. © 2016 John Wiley & Sons Ltd.

  15. Inflammatory bowel disease and irritable bowel syndrome: similarities and differences.

    Science.gov (United States)

    Barbara, Giovanni; Cremon, Cesare; Stanghellini, Vincenzo

    2014-07-01

    Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are classically viewed as dichotomous conditions. The former is perceived as a typical organic disease, and the latter is regarded as a disorder of gut function driven by mood. Recent research identified some shared contributing factors, which will be discussed here. Mounting evidence shows the importance in both IBD and IBS of genetic, microbiological, epithelial, and immunological factors. In some instances, these factors overlap in the two conditions as shown by: involvement of brain-gut axis dysfunction in IBD, implication of TNFSF gene in Crohn's disease and IBS, evidence of abnormal microbiota and its impact on host functions, identification of low-grade inflammation in subsets of IBS patients, and development of IBS symptoms in patients with IBD in remission. IBD and IBS remain separate conditions although there are some overlapping mechanisms. Both research and clinical management would benefit from considering a functional approach for certain manifestations of IBD and accepting an organic view in subsets of IBS patients.

  16. Crystal structure of Lymnaea stagnalis AChBP complexed with the potent nAChR antagonist DHβE suggests a unique mode of antagonism.

    Directory of Open Access Journals (Sweden)

    Azadeh Shahsavar

    Full Text Available Nicotinic acetylcholine receptors (nAChRs are pentameric ligand-gated ion channels that belong to the Cys-loop receptor superfamily. These receptors are allosteric proteins that exist in different conformational states, including resting (closed, activated (open, and desensitized (closed states. The acetylcholine binding protein (AChBP is a structural homologue of the extracellular ligand-binding domain of nAChRs. In previous studies, the degree of the C-loop radial extension of AChBP has been assigned to different conformational states of nAChRs. It has been suggested that a closed C-loop is preferred for the active conformation of nAChRs in complex with agonists whereas an open C-loop reflects an antagonist-bound (closed state. In this work, we have determined the crystal structure of AChBP from the water snail Lymnaea stagnalis (Ls in complex with dihydro-β-erythroidine (DHβE, which is a potent competitive antagonist of nAChRs. The structure reveals that binding of DHβE to AChBP imposes closure of the C-loop as agonists, but also a shift perpendicular to previously observed C-loop movements. These observations suggest that DHβE may antagonize the receptor via a different mechanism compared to prototypical antagonists and toxins.

  17. Group hypnotherapy for irritable bowel syndrome with long-term follow-up.

    Science.gov (United States)

    Gerson, Charles D; Gerson, Jessica; Gerson, Mary-Joan

    2013-01-01

    This study tested whether group gut-focused hypnotherapy would improve irritable bowel syndrome (IBS). Several possible outcome predictors were also studied. Before treatment, 75 patients completed a Symptom Severity Scale, a Mind-Body attribution questionnaire, and a Quality of Relationship Inventory (QRI). The symptom scale was completed posttreatment, 3, 6, and 12 months later. There was significant symptom reduction at each data point (p hypnotherapy, while attribution of symptoms to mind (emotional) causation was inversely correlated (p = .0056). The authors conclude that group hypnotherapy is effective in patients with IBS.

  18. Chlorpyrifos and Malathion have opposite effects on behaviors and brain size that are not correlated to changes in AChE activity

    Science.gov (United States)

    Richendrfer, Holly; Creton, Robbert

    2015-01-01

    Organophosphates, a type of neurotoxicant pesticide, are used globally for the treatment of pests on croplands and are therefore found in a large number of conventional foods. These pesticides are harmful and potentially deadly if ingested or inhaled in large quantities by causing a significant reduction in acetylcholinesterase (AChE) activity in the central and peripheral nervous system. However, much less is known about the effects of exposure to small quantities of the pesticides on neural systems and behavior during development. In the current study we used zebrafish larvae in order to determine the effects of two of the most widely used organophosphates, chlorpyrifos and malathion, on zebrafish behavior and AChE activity. Embryos and larvae were exposed to the organophosphates during different time points in development and then tested at 5 days post-fertilization for behavioral, neurodevelopmental and AChE abnormalities. The results of the study indicate that chlorpyrifos and malathion cause opposing behaviors in the larvae such as swim speed (hypoactivity vs. hyperactivity) and rest. Additionally, the pesticides affect only certain behaviors, such as thigmotaxis, during specific time points in development that are unrelated to changes in AChE activity. Larvae treated with malathion but not chlorpyrifos also had significantly smaller forebrain and hindbrain regions compared to controls by 5 days post-fertilization. We conclude that exposure to very low concentrations of organophosphate pesticides during development cause abnormalities in behavior and brain size. PMID:25983063

  19. Chlorpyrifos and malathion have opposite effects on behaviors and brain size that are not correlated to changes in AChE activity.

    Science.gov (United States)

    Richendrfer, Holly; Creton, Robbert

    2015-07-01

    Organophosphates, a type of neurotoxicant pesticide, are used globally for the treatment of pests on croplands and are therefore found in a large number of conventional foods. These pesticides are harmful and potentially deadly if ingested or inhaled in large quantities by causing a significant reduction in acetylcholinesterase (AChE) activity in the central and peripheral nervous system. However, much less is known about the effects of exposure to small quantities of the pesticides on neural systems and behavior during development. In the current study we used zebrafish larvae in order to determine the effects of two of the most widely used organophosphates, chlorpyrifos and malathion, on zebrafish behavior and AChE activity. Embryos and larvae were exposed to the organophosphates during different time points in development and then tested at 5 days post-fertilization for behavioral, neurodevelopmental and AChE abnormalities. The results of the study indicate that chlorpyrifos and malathion cause opposing behaviors in the larvae such as swim speed (hypoactivity vs. hyperactivity) and rest. Additionally, the pesticides affect only certain behaviors, such as thigmotaxis, during specific time points in development that are unrelated to changes in AChE activity. Larvae treated with malathion but not chlorpyrifos also had significantly smaller forebrain and hindbrain regions compared to controls by 5 days post-fertilization. We conclude that exposure to very low concentrations of organophosphate pesticides during development cause abnormalities in behavior and brain size. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Gut inflammation in chronic fatigue syndrome

    Directory of Open Access Journals (Sweden)

    Kirchgessner Annette

    2010-10-01

    Full Text Available Abstract Chronic fatigue syndrome (CFS is a debilitating disease characterized by unexplained disabling fatigue and a combination of accompanying symptoms the pathology of which is incompletely understood. Many CFS patients complain of gut dysfunction. In fact, patients with CFS are more likely to report a previous diagnosis of irritable bowel syndrome (IBS, a common functional disorder of the gut, and experience IBS-related symptoms. Recently, evidence for interactions between the intestinal microbiota, mucosal barrier function, and the immune system have been shown to play a role in the disorder's pathogenesis. Studies examining the microecology of the gastrointestinal (GI tract have identified specific microorganisms whose presence appears related to disease; in CFS, a role for altered intestinal microbiota in the pathogenesis of the disease has recently been suggested. Mucosal barrier dysfunction promoting bacterial translocation has also been observed. Finally, an altered mucosal immune system has been associated with the disease. In this article, we discuss the interplay between these factors in CFS and how they could play a significant role in GI dysfunction by modulating the activity of the enteric nervous system, the intrinsic innervation of the gut. If an altered intestinal microbiota, mucosal barrier dysfunction, and aberrant intestinal immunity contribute to the pathogenesis of CFS, therapeutic efforts to modify gut microbiota could be a means to modulate the development and/or progression of this disorder. For example, the administration of probiotics could alter the gut microbiota, improve mucosal barrier function, decrease pro-inflammatory cytokines, and have the potential to positively influence mood in patients where both emotional symptoms and inflammatory immune signals are elevated. Probiotics also have the potential to improve gut motility, which is dysfunctional in many CFS patients.

  1. [Gut microbiota in health and disease].

    Science.gov (United States)

    Icaza-Chávez, M E

    2013-01-01

    Gut microbiota is the community of live microorganisms residing in the digestive tract. There are many groups of researchers worldwide that are working at deciphering the collective genome of the human microbiota. Modern techniques for studying the microbiota have made us aware of an important number of nonculturable bacteria and of the relation between the microorganisms that live inside us and our homeostasis. The microbiota is essential for correct body growth, the development of immunity, and nutrition. Certain epidemics affecting humanity such as asthma and obesity may possibly be explained, at least partially, by alterations in the microbiota. Dysbiosis has been associated with a series of gastrointestinal disorders that include non-alcoholic fatty liver disease, celiac disease, and irritable bowel syndrome. The present article deals with the nomenclature, modern study techniques, and functions of gut microbiota, and its relation to health and disease. Copyright © 2013 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

  2. Bacteria, genetics and irritable bowel syndrome.

    LENUS (Irish Health Repository)

    Craig, Orla F

    2010-06-01

    EVALUATION OF: Villani AC, Lemire M, Thabane M et al. Genetic risk factors for post-infectious irritable bowel syndrome following a waterborne outbreak of gastroenteritis. Gastroenterology 138, 1502-1513 (2010). While the pathogenesis of irritable bowel syndrome (IBS) remains to be fully defined, two clinical observations - the occurrence, de novo, of IBS following bacterial gastroenteritis and the history, commonly obtained from IBS patients, of other instances of the syndrome within their families - have instigated investigations, in IBS, of the potential roles, on the one hand, of the gut microbiota and the host response and, on the other hand, of genetic factors. The study reviewed here relates to both of these factors by studying genetic predisposition to postinfective IBS in a large population of individuals who were exposed to a multimicrobial enteric infection, which resulted in a severe outbreak of gastroenteritis and was followed by the development of IBS in over a third. In this detailed study, the investigators identified a number of genes that were linked significantly to the development of postinfectious-IBS in the Toll-like receptor 9, IL-6 and cadherin 1 regions. These genes play important roles in bacterial recognition, the inflammatory response and epithelial integrity, respectively, and provide considerable support for the hypothesis that links IBS onset to disturbances in the microbiota and the host response.

  3. A psychology of the human brain-gut-microbiome axis.

    Science.gov (United States)

    Allen, Andrew P; Dinan, Timothy G; Clarke, Gerard; Cryan, John F

    2017-04-01

    In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain-gut-microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress-related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain-gut-microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain-gut-microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain-gut-microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain-gut-microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology.

  4. The Potential for Gut Organoid Derived Interstitial Cells of Cajal in Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Jerry Zhou

    2017-09-01

    Full Text Available Effective digestion requires propagation of food along the entire length of the gastrointestinal tract. This process involves coordinated waves of peristalsis produced by enteric neural cell types, including different categories of interstitial cells of Cajal (ICC. Impaired food transport along the gastrointestinal tract, either too fast or too slow, causes a range of gut motility disorders that affect millions of people worldwide. Notably, loss of ICC has been shown to affect gut motility. Patients that suffer from gut motility disorders regularly experience diarrhoea and/or constipation, insomnia, anxiety, attention lapses, irritability, dizziness, and headaches that greatly affect both physical and mental health. Limited treatment options are available for these patients, due to the scarcity of human gut tissue for research and transplantation. Recent advances in stem cell technology suggest that large amounts of rudimentary, yet functional, human gut tissue can be generated in vitro for research applications. Intriguingly, these stem cell-derived gut organoids appear to contain functional ICC, although their frequency and functional properties are yet to be fully characterised. By reviewing methods of gut organoid generation, together with what is known of the molecular and functional characteristics of ICC, this article highlights short- and long-term goals that need to be overcome in order to develop ICC-based therapies for gut motility disorders.

  5. [Parasitosis and irritable bowel syndrome].

    Science.gov (United States)

    Ibarra, Catalina; Herrera, Valentina; Pérez de Arce, Edith; Gil, Luis Carlos; Madrid, Ana María; Valenzuela, Lucía; Beltrán, Caroll J

    2016-06-01

    Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal tract characterised by multi-factorial aetiology. In IBS physiopathology are involved diverse factors between them biological, psychosocial, and environmental components which affect the immune activation status of gut mucosa. Among these factors is recognized the intestinal parasitosis. Post-infection IBS (PI-IBS) is recognised as a subgroup of functional disorders whose symptoms onset appear after a symptomatic intestinal infection caused by microbial agents. There are few studies regarding of relationship between IBS and intestinal parasitosis in Chile. However, is has been well described a positive association between IBS and Blastocystis hominis infections, one of prevalent parasites in Chile. In other countries, is also described a relationship between IBS and amebiasis and giardiasis. Both, characterized by a common mode of transmission through water as well as contaminated food. Because the high prevalence of parasitosis in our country it is necessary to expand the association studies to clarify the strength of the parasites ethiology in IBS.

  6. Escherichia coli Protein Expression System for Acetylcholine Binding Proteins (AChBPs.

    Directory of Open Access Journals (Sweden)

    Nikita Abraham

    Full Text Available Nicotinic acetylcholine receptors (nAChR are ligand gated ion channels, identified as therapeutic targets for a range of human diseases. Drug design for nAChR related disorders is increasingly using structure-based approaches. Many of these structural insights for therapeutic lead development have been obtained from co-crystal structures of nAChR agonists and antagonists with the acetylcholine binding protein (AChBP. AChBP is a water soluble, structural and functional homolog of the extracellular, ligand-binding domain of nAChRs. Currently, AChBPs are recombinantly expressed in eukaryotic expression systems for structural and biophysical studies. Here, we report the establishment of an Escherichia coli (E. coli expression system that significantly reduces the cost and time of production compared to the existing expression systems. E. coli can efficiently express unglycosylated AChBP for crystallography and makes the expression of isotopically labelled forms feasible for NMR. We used a pHUE vector containing an N-terminal His-tagged ubiquitin fusion protein to facilitate AChBP expression in the soluble fractions, and thus avoid the need to recover protein from inclusion bodies. The purified protein yield obtained from the E. coli expression system is comparable to that obtained from existing AChBP expression systems. E. coli expressed AChBP bound nAChR agonists and antagonists with affinities matching those previously reported. Thus, the E. coli expression system significantly simplifies the expression and purification of functional AChBP for structural and biophysical studies.

  7. Maternal separation as a model of brain-gut axis dysfunction.

    LENUS (Irish Health Repository)

    O'Mahony, Siobhain M

    2011-03-01

    Early life stress has been implicated in many psychiatric disorders ranging from depression to anxiety. Maternal separation in rodents is a well-studied model of early life stress. However, stress during this critical period also induces alterations in many systems throughout the body. Thus, a variety of other disorders that are associated with adverse early life events are often comorbid with psychiatric illnesses, suggesting a common underlying aetiology. Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that is thought to involve a dysfunctional interaction between the brain and the gut. Essential aspects of the brain-gut axis include spinal pathways, the hypothalamic pituitary adrenal axis, the immune system, as well as the enteric microbiota. Accumulating evidence suggest that stress, especially in early life, is a predisposing factor to IBS.

  8. Discovery of potent and selective acetylcholinesterase (AChE) inhibitors: acacetin 7-O-methyl ether Mannich base derivatives synthesised from easy access natural product naringin.

    Science.gov (United States)

    Liu, Hao-Ran; Men, Xue; Gao, Xiao-Hui; Liu, Lin-Bo; Fan, Hao-Qun; Xia, Xin-Hua; Wang, Qiu-An

    2018-03-01

    Naringin, as a component universal existing in the peel of some fruits or medicinal plants, was usually selected as the material to synthesise bioactive derivates since it was easy to gain with low cost. In present investigation, eight new acacetin-7-O-methyl ether Mannich base derivatives (1-8) were synthesised from naringin. The bioactivity evaluation revealed that most of them exhibited moderate or potent acetylcholinesterase (AChE) inhibitory activity. Among them, compound 7 (IC 50 for AChE = 0.82 ± 0.08 μmol•L -1 , IC 50 for BuChE = 46.30 ± 3.26 μmol•L -1 ) showed a potent activity and high selectivity compared with the positive control Rivastigmine (IC 50 for AChE = 10.54 ± 0.86 μmol•L -1 , IC 50 for BuChE = 0.26 ± 0.08 μmol•L -1 ). The kinetic study suggested that compound 7 bind to AChE with mix-type inhibitory profile. Molecular docking study revealed that compound 7 could combine both catalytic active site (CAS) and peripheral active site (PAS) of AChE with four points (Trp84, Trp279, Tyr70 and Phe330), while it could bind with BuChE via only His 20.

  9. Peripheral Inhibitor of AChE, Neostigmine, Prevents the Inflammatory Dependent Suppression of GnRH/LH Secretion during the Follicular Phase of the Estrous Cycle

    Directory of Open Access Journals (Sweden)

    Andrzej P. Herman

    2017-01-01

    Full Text Available The study was designed to test the hypothesis that the inhibition of acetylcholinesterase (AChE activity at the periphery by Neostigmine (0.5 mg/animal will be sufficient to prevent inflammatory dependent suppression of the gonadotropin-releasing hormone (GnRH/luteinising hormone (LH secretion in ewes in the follicular phase of the estrous cycle, and this effect will be comparable with the systemic AChE inhibitor, Donepezil (2.5 mg/animal. An immune/inflammatory challenge was induced by peripheral administration of lipopolysaccharide (LPS; 400 ng/kg. Peripheral treatment with Donepezil and Neostigmine prevented the LPS-induced decrease (P<0.05 in LHβ gene expression in the anterior pituitary gland (AP and in LH release. Moreover, Donepezil completely abolished (P<0.05 the suppressory effect of inflammation on GnRH synthesis in the preoptic area, when pretreatment with Neostigmine reduced (P<0.05 the decrease in GnRH content in this hypothalamic structure. Moreover, administration of both AChE inhibitors diminished (P<0.05 the inhibitory effect of LPS treatment on the expression of GnRH receptor in the AP. Our study shows that inflammatory dependent changes in the GnRH/LH secretion may be eliminated or reduced by AChE inhibitors suppressing inflammatory reaction only at the periphery such as Neostigmine, without the need for interfering in the central nervous system.

  10. Review of Rifaximin: Latest Treatment Frontier for Irritable Bowel Syndrome Mechanism of Action and Clinical Profile

    Directory of Open Access Journals (Sweden)

    Kamesh Gupta

    2017-08-01

    Full Text Available Background: Irritable bowel syndrome is classified as a functional gastrointestinal disorder with the primary symptom of abdominal pain in conjunction with bloating and bowel movement disorder. It affects up to 15% of the world’s population. Among its subtypes, the most common is diarrhoea predominant. However, the current treatment options for diarrhoea-predominant irritable bowel syndrome have had not very promising results; most, such as antispasmodics, only provide partial symptomatic relief. Treatment with antidepressants and alosetron (a 5HT3 antagonist has shown the most promise to date. The latest drug to be approved for the treatment of irritable bowel syndrome-diarrhoea is rifaximin, which was approved in May 2015. It is a minimally absorbed antibiotic that is used to change the gut microbiota. Small intestinal bacterial overgrowth is one of the causes suggested for irritable bowel syndrome, particularly for the diarrhoea-predominant type. There are various methods for detecting bacterial overgrowth, the simplest of which is breath tests. Rifaximin has been shown to be of benefit to these patients. Purpose: The purpose of the study is to discuss the potential mechanism of action of rifaximin, a minimally absorbed antibiotic. In addition, we evaluate the various clinical trials undertaken to study the efficacy and safety profile of rifaximin.

  11. Role of negative affects in pathophysiology and clinical expression of irritable bowel syndrome.

    Science.gov (United States)

    Muscatello, Maria Rosaria A; Bruno, Antonio; Scimeca, Giuseppe; Pandolfo, Gianluca; Zoccali, Rocco A

    2014-06-28

    Irritable bowel syndrome (IBS) is regarded as a multifactorial disease in which alterations in the brain-gut axis signaling play a major role. The biopsychosocial model applied to the understanding of IBS pathophysiology assumes that psychosocial factors, interacting with peripheral/central neuroendocrine and immune changes, may induce symptoms of IBS, modulate symptom severity, influence illness experience and quality of life, and affect outcome. The present review focuses on the role of negative affects, including depression, anxiety, and anger, on pathogenesis and clinical expression of IBS. The potential role of the autonomic nervous system, stress-hormone system, and immune system in the pathophysiology of both negative affects and IBS are taken into account. Psychiatric comorbidity and subclinical variations in levels of depression, anxiety, and anger are further discussed in relation to the main pathophysiological and symptomatic correlates of IBS, such as sensorimotor functions, gut microbiota, inflammation/immunity, and symptom reporting.

  12. Long-term effects of hypnotherapy in patients with refractory irritable bowel syndrome.

    Science.gov (United States)

    Lindfors, Perjohan; Unge, Peter; Nyhlin, Henry; Ljótsson, Brjánn; Björnsson, Einar S; Abrahamsson, Hasse; Simrén, Magnus

    2012-04-01

    Gut-directed hypnotherapy is considered to be an effective treatment in irritable bowel syndrome (IBS) but few studies report the long-term effects. This retrospective study aims to evaluate the long-term perceived efficacy of gut-directed hypnotherapy given outside highly specialized hypnotherapy centers. 208 patients, who all had received gut-directed hypnotherapy, were retrospectively evaluated. The Subjective Assessment Questionnaire (SAQ) was used to measure changes in IBS symptoms, and patients were classified as responders and non-responders. Patients were also asked to report changes in health-care seeking, use of drugs for IBS symptoms, use of alternative non-pharmacological treatments, and if they still actively used hypnotherapy. Immediately after hypnotherapy, 103 of 208 patients (49%) were responders and 75 of these (73%) had improved further at the follow-up 2-7 years after hypnotherapy (mean 4 years). A majority of the responders still used hypnotherapy on a regular basis at follow-up (73%), and the responders reported a greater reduction in health-care seeking than non-responders. A total of 87% of all patients reported that they considered gut-directed hypnotherapy to be worthwhile, and this differed between responders and non-responders (100% vs. 74%; p hypnotherapy in refractory IBS is an effective treatment option with long-lasting effects, also when given outside highly specialized hypnotherapy centers. Apart from the clinical benefits, the reduction in health-care utilization has the potential to reduce the health-care costs.

  13. From the Bottom-Up: Chemotherapy and Gut-Brain Axis Dysregulation.

    Science.gov (United States)

    Bajic, Juliana E; Johnston, Ian N; Howarth, Gordon S; Hutchinson, Mark R

    2018-01-01

    The central nervous system and gastrointestinal tract form the primary targets of chemotherapy-induced toxicities. Symptoms associated with damage to these regions have been clinically termed chemotherapy-induced cognitive impairment and mucositis. Whilst extensive literature outlines the complex etiology of each pathology, to date neither chemotherapy-induced side-effect has considered the potential impact of one on the pathogenesis of the other disorder. This is surprising considering the close bidirectional relationship shared between each organ; the gut-brain axis. There are complex multiple pathways linking the gut to the brain and vice versa in both normal physiological function and disease. For instance, psychological and social factors influence motility and digestive function, symptom perception, and behaviors associated with illness and pathological outcomes. On the other hand, visceral pain affects central nociception pathways, mood and behavior. Recent interest highlights the influence of functional gut disorders, such as inflammatory bowel diseases and irritable bowel syndrome in the development of central comorbidities. Gut-brain axis dysfunction and microbiota dysbiosis have served as key portals in understanding the potential mechanisms associated with these functional gut disorders and their effects on cognition. In this review we will present the role gut-brain axis dysregulation plays in the chemotherapy setting, highlighting peripheral-to-central immune signaling mechanisms and their contribution to neuroimmunological changes associated with chemotherapy exposure. Here, we hypothesize that dysregulation of the gut-brain axis plays a major role in the intestinal, psychological and neurological complications following chemotherapy. We pay particular attention to evidence surrounding microbiota dysbiosis, the role of intestinal permeability, damage to nerves of the enteric and peripheral nervous systems and vagal and humoral mediated changes.

  14. Mechanisms of Stress-Induced Visceral Pain: Implications in Irritable Bowel Syndrome.

    Science.gov (United States)

    Greenwood-Van Meerveld, B; Moloney, R D; Johnson, A C; Vicario, M

    2016-08-01

    Visceral pain is a term describing pain originating from the internal organs of the body and is a common feature of many disorders, including irritable bowel syndrome (IBS). Stress is implicated in the development and exacerbation of many visceral pain disorders. Recent evidence suggests that stress and the gut microbiota can interact through complementary or opposing factors to influence visceral nociceptive behaviours. The Young Investigator Forum at the International Society of Psychoneuroendocrinology (ISPNE) annual meeting reported experimental evidence suggesting the gut microbiota can affect the stress response to affect visceral pain. Building upon human imaging data showing abnormalities in the central processing of visceral stimuli in patients with IBS and knowledge that the amygdala plays a pivotal role in facilitating the stress axis, the latest experimental evidence supporting amygdala-mediated mechanisms in stress-induced visceral pain was reviewed. The final part of the session at ISPNE reviewed experimental evidence suggesting that visceral pain in IBS may be a result, at least in part, of afferent nerve sensitisation following increases in epithelial permeability and mucosal immune activation. © 2016 British Society for Neuroendocrinology.

  15. Revealing the importance of linkers in K-series oxime reactivators for tabun-inhibited AChE using quantum chemical, docking and SMD studies.

    Science.gov (United States)

    Ghosh, Shibaji; Chandar, Nellore Bhanu; Jana, Kalyanashis; Ganguly, Bishwajit

    2017-08-01

    Inhibition of acetylcholinesterase (AChE) with organophosphorus compounds has a detrimental effect on human life. Oxime K203 seems to be one of the promising reactivators for tabun-inhibited AChE than (K027, K127, and K628). These reactivators differ only in the linker units between the two pyridinium rings. The conformational analyses performed with quantum chemical RHF/6-31G* level for K027, K127, K203 and K628 showed that the minimum energy conformers have different orientations of the active and peripheral pyridinium rings for these reactivator molecules. K203 with (-CH 2 -CH=CH-CH 2 -) linker unit possesses more open conformation compared to the other reactivators. Such orientation of K203 experiences favorable interaction with the surrounding residues of catalytic anionic site (CAS) and peripheral anionic site (PAS) of tabun-inhibited AChE. From the steered molecular dynamics simulations, it has been observed that the oxygen atom of the oxime group of K203 reactivator approaches nearest to the P-atom of the SUN203 (3.75 Å) at lower time scales (less than ~1000 ps) as compared to the other reactivators. K203 experiences less number of hydrophobic interaction with the PAS residues which is suggested to be an important factor for the efficient reactivation process. In addition, K203 crates large number of H-bonding with CAS residues SUN203, Phe295, Tyr337, Phe338 and His447. K203 barely changes its conformation during the SMD simulation process and hence the energy penalty to adopt any other conformation is minimal in this case as compared to the other reactivators. The molecular mechanics and Poisson-Boltzmann surface area binding energies obtained for the interaction of K203 inside the gorge of tabun inhibited AChE is substantially higher (-290.2 kcal/mol) than the corresponding K628 reactivator (-260.4 kcal/mol), which also possess unsaturated aromatic linker unit.

  16. Revealing the importance of linkers in K-series oxime reactivators for tabun-inhibited AChE using quantum chemical, docking and SMD studies

    Science.gov (United States)

    Ghosh, Shibaji; Chandar, Nellore Bhanu; Jana, Kalyanashis; Ganguly, Bishwajit

    2017-08-01

    Inhibition of acetylcholinesterase (AChE) with organophosphorus compounds has a detrimental effect on human life. Oxime K203 seems to be one of the promising reactivators for tabun-inhibited AChE than (K027, K127, and K628). These reactivators differ only in the linker units between the two pyridinium rings. The conformational analyses performed with quantum chemical RHF/6-31G* level for K027, K127, K203 and K628 showed that the minimum energy conformers have different orientations of the active and peripheral pyridinium rings for these reactivator molecules. K203 with (-CH2-CH=CH-CH2-) linker unit possesses more open conformation compared to the other reactivators. Such orientation of K203 experiences favorable interaction with the surrounding residues of catalytic anionic site (CAS) and peripheral anionic site (PAS) of tabun-inhibited AChE. From the steered molecular dynamics simulations, it has been observed that the oxygen atom of the oxime group of K203 reactivator approaches nearest to the P-atom of the SUN203 (3.75 Å) at lower time scales (less than 1000 ps) as compared to the other reactivators. K203 experiences less number of hydrophobic interaction with the PAS residues which is suggested to be an important factor for the efficient reactivation process. In addition, K203 crates large number of H-bonding with CAS residues SUN203, Phe295, Tyr337, Phe338 and His447. K203 barely changes its conformation during the SMD simulation process and hence the energy penalty to adopt any other conformation is minimal in this case as compared to the other reactivators. The molecular mechanics and Poisson-Boltzmann surface area binding energies obtained for the interaction of K203 inside the gorge of tabun inhibited AChE is substantially higher (-290.2 kcal/mol) than the corresponding K628 reactivator (-260.4 kcal/mol), which also possess unsaturated aromatic linker unit.

  17. Therapies aimed at the gut microbiota and inflammation: antibiotics, prebiotics, probiotics, synbiotics, anti-inflammatory therapies.

    LENUS (Irish Health Repository)

    Quigley, Eamonn M M

    2011-03-01

    Several recent observations have raised the possibility that disturbances in the gut microbiota and\\/or a low-grade inflammatory state may contribute to symptomatology and the etiology of irritable bowel syndrome (IBS). Consequent on these hypotheses, several therapeutic categories have found their way into the armamentarium of those who care for IBS sufferers. These agents include probiotics, prebiotics, antibiotics, and anti-inflammatory agents.

  18. Facile synthesis of new carbon-11 labeled conformationally restricted rivastigmine analogues as potential PET agents for imaging AChE and BChE enzymes

    International Nuclear Information System (INIS)

    Wang Min; Wang Jiquan; Gao Mingzhang; Zheng Qihuang

    2008-01-01

    Rivastigmine is a newer-generation inhibitor with a dual inhibitory action on both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes, and is used for the treatment of AChE- and BChE-related diseases such as brain Alzheimer's disease and cardiovascular disease. New carbon-11 labeled conformationally restricted rivastigmine analogues radiolabeled quaternary ammonium triflate salts, (3aR,9bS)-1-[ 11 C]methyl-1-methyl-6-(methylcarbamoyloxy)-2,3,3a,4,5, 9b-hexahy dro-1H-benzo[g]indolium triflate ([ 11 C]8) and (3aR,9bS)-1-[ 11 C]methyl-1-methyl-6-(heptylcarbamoyloxy)-2,3,3a,4,5, 9b-hexahy dro-1H-benzo[g]indolium triflate ([ 11 C]9), were designed and synthesized as potential positron emission tomography (PET) agents for imaging AChE and BChE enzymes. The appropriate precursors were labeled with [ 11 C]CH 3 OTf through N-[ 11 C]methylation, and the target tracers were isolated by solid-phase extraction (SPE) using a cation-exchange CM Sep-Pak cartridge in 40-50% radiochemical yields decay corrected to end of bombardment (EOB), 15-20 min overall synthesis time, and 148-222 GBq/μmol specific activity at EOB

  19. Repeated administration of alpha7 nicotinic acetylcholine receptor (nAChR) agonists, but not positive allosteric modulators, increases alpha7 nAChR levels in the brain

    DEFF Research Database (Denmark)

    Christensen, Ditte Z; Mikkelsen, Jens D; Hansen, Henrik H

    2010-01-01

    AChR binding sites in several brain regions, particularly in the prefrontal cortex. The alpha7 nAChR agonists SSR180711 and PNU-282987 also increase [(125)I]-BTX binding, suggesting that this is a general consequence of alpha7 nAChR agonism. Interestingly, the alpha7 nAChR positive allosteric modulators PNU......The alpha7 nicotinic acetylcholine receptor (nAChR) is an important target for treatment of cognitive deficits in schizophrenia and Alzheimer's disease. However, the receptor desensitizes rapidly in vitro, which has led to concern regarding its applicability as a clinically relevant drug target....... Here we investigate the effects of repeated agonism on alpha7 nAChR receptor levels and responsiveness in vivo in rats. Using [(125)I]-alpha-bungarotoxin (BTX) autoradiography we show that acute or repeated administration with the selective alpha7 nAChR agonist A-582941 increases the number of alpha7 n...

  20. AChR-specific immunosuppressive therapy of myasthenia gravis.

    Science.gov (United States)

    Luo, Jie; Lindstrom, Jon

    2015-10-15

    Myasthenia gravis (MG) is an organ-specific autoimmune disease characterized by muscle fatigability. In most cases, it is mediated by autoantibodies targeting muscle nicotinic acetylcholine receptors (AChRs) at the neuromuscular junction. Experimental autoimmune myasthenia gravis (EAMG) is an animal model for MG, which is usually induced by immunization with AChR purified from fish electric organ. Pathological autoantibodies to AChRs are directed at the extracellular surface, especially the main immunogenic region (MIR). Current treatments for MG can help many but not all patients. Antigen-specific immunosuppressive therapy for MG that specifically suppresses the autoimmune response without affecting the entire immune system and avoids side effects of general immunosuppression is currently unavailable. Early attempts at antigen-specific immunosuppression for EAMG using AChR extracellular domain sequences that form epitopes for pathological autoantibodies risked provoking autoimmunity rather than suppressing it. We discovered a novel approach to specific immunosuppression of EAMG with a therapeutic vaccine consisting of bacterially-expressed human AChR cytoplasmic domains, which has the potential to specifically suppress MG without danger of causing exacerbation. This approach prevents development of chronic EAMG when initiated immediately after the acute phase of EAMG, and rapidly reverses established chronic EAMG when started during the chronic phase of EAMG. Successfully treated rats exhibited long-term resistance to re-induction of EAMG. In this review we also discuss the current understanding of the mechanisms by which the therapy works. Vaccination with AChR cytoplasmic domains in adjuvant is promising as a safe, antigen-specific, potent, effective, rapidly acting, and long lasting approach to therapy of MG. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. A Green Method for Synthesis of 7H-thiazolo[3,2-b][1,2, 4]-triazin-7-one Derivatives as AChE Inhibitors

    Directory of Open Access Journals (Sweden)

    Liu Sijie

    2015-01-01

    Full Text Available The authors study an efficient and green approach for the synthesis of 7H-thiazolo [3, 2-b][1,2,4]triazin-7-one derivatives as AChE inhibitors. The 7H-thiazolo[3,2-b][1,2,4]triazin-7-ones were designed by molecular docking, and readily prepared via a one-pot reaction in morpholine hydrosulfate ([Hnhm]HSO4 lonic liquid as the catalyst and solvent. The study of AChE inhibitory activity was carried out through using the Ellman colorimetric assay. The 7H-thiazolo[3,2-b][1,2,4]triazin-7-ones had been successfully synthesized by green catalyst. Most of the target compounds exhibited more than 50% inhibition at 10μM.

  2. Intestinal microbiota in pathophysiology and management of irritable bowel syndrome

    Science.gov (United States)

    Lee, Kang Nyeong; Lee, Oh Young

    2014-01-01

    Irritable bowel syndrome (IBS) is a functional bowel disorder without any structural or metabolic abnormalities that sufficiently explain the symptoms, which include abdominal pain and discomfort, and bowel habit changes such as diarrhea and constipation. Its pathogenesis is multifactorial: visceral hypersensitivity, dysmotility, psychosocial factors, genetic or environmental factors, dysregulation of the brain-gut axis, and altered intestinal microbiota have all been proposed as possible causes. The human intestinal microbiota are composed of more than 1000 different bacterial species and 1014 cells, and are essential for the development, function, and homeostasis of the intestine, and for individual health. The putative mechanisms that explain the role of microbiota in the development of IBS include altered composition or metabolic activity of the microbiota, mucosal immune activation and inflammation, increased intestinal permeability and impaired mucosal barrier function, sensory-motor disturbances provoked by the microbiota, and a disturbed gut-microbiota-brain axis. Therefore, modulation of the intestinal microbiota through dietary changes, and use of antibiotics, probiotics, and anti-inflammatory agents has been suggested as strategies for managing IBS symptoms. This review summarizes and discusses the accumulating evidence that intestinal microbiota play a role in the pathophysiology and management of IBS. PMID:25083061

  3. Intestinal microbiota in pathophysiology and management of irritable bowel syndrome.

    Science.gov (United States)

    Lee, Kang Nyeong; Lee, Oh Young

    2014-07-21

    Irritable bowel syndrome (IBS) is a functional bowel disorder without any structural or metabolic abnormalities that sufficiently explain the symptoms, which include abdominal pain and discomfort, and bowel habit changes such as diarrhea and constipation. Its pathogenesis is multifactorial: visceral hypersensitivity, dysmotility, psychosocial factors, genetic or environmental factors, dysregulation of the brain-gut axis, and altered intestinal microbiota have all been proposed as possible causes. The human intestinal microbiota are composed of more than 1000 different bacterial species and 10(14) cells, and are essential for the development, function, and homeostasis of the intestine, and for individual health. The putative mechanisms that explain the role of microbiota in the development of IBS include altered composition or metabolic activity of the microbiota, mucosal immune activation and inflammation, increased intestinal permeability and impaired mucosal barrier function, sensory-motor disturbances provoked by the microbiota, and a disturbed gut-microbiota-brain axis. Therefore, modulation of the intestinal microbiota through dietary changes, and use of antibiotics, probiotics, and anti-inflammatory agents has been suggested as strategies for managing IBS symptoms. This review summarizes and discusses the accumulating evidence that intestinal microbiota play a role in the pathophysiology and management of IBS.

  4. No change in rectal sensitivity after gut-directed hypnotherapy in children with functional abdominal pain or irritable bowel syndrome.

    Science.gov (United States)

    Vlieger, A M; van den Berg, M M; Menko-Frankenhuis, C; Bongers, M E J; Tromp, E; Benninga, M A

    2010-01-01

    Gut-directed hypnotherapy (HT) has recently been shown to be highly effective in treating children with functional abdominal pain (FAP) and irritable bowel syndrome (IBS). This study was conducted to determine the extent to which this treatment success is because of an improvement in rectal sensitivity. A total of 46 patients (aged 8-18 years) with FAP (n=28) or IBS (n=18) were randomized to either 12 weeks of standard medical therapy (SMT) or HT. To assess rectal sensitivity, a pressure-controlled intermittent distension protocol (barostat) was performed before and after the therapy. Rectal sensitivity scores changed in SMT patients from 15.1+/-7.3 mm Hg at baseline to 18.6+/-8.5 mm Hg after 12 weeks of treatment (P=0.09) and in HT patients from 17.0+/-9.2 mm Hg to 22.5+/-10.1 mm Hg (P=0.09). The number of patients with rectal hypersensitivity decreased from 6 of 18 to 0 of 18 in the HT group (P=0.04) vs. 6 of 20 to 4 of 20 in the SMT group (P=0.67). No relationship was established between treatment success and rectal pain thresholds. Rectal sensitivity scores at baseline were not correlated with intensity, frequency, or duration of abdominal pain. Clinical success achieved with HT cannot be explained by improvement in rectal sensitivity. Furthermore, no association could be found between rectal barostat findings and clinical symptoms in children with FAP or IBS. Further studies are necessary to shed more light on both the role of rectal sensitivity in pediatric FAP and IBS and the mechanisms by which hypnotherapy results in improvement of clinical symptoms.

  5. Insect nicotinic acetylcholine receptors (nAChRs): Important amino ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-29

    Dec 29, 2008 ... nAChRs within the insect central nervous system has led to the development of insecticides targeting .... binding protein (AChBP), a homopentameric structural and functional homolog of ..... of the honey bee, Apis mellifera.

  6. Sex hormones in the modulation of irritable bowel syndrome.

    Science.gov (United States)

    Mulak, Agata; Taché, Yvette; Larauche, Muriel

    2014-03-14

    Compelling evidence indicates sex and gender differences in epidemiology, symptomatology, pathophysiology, and treatment outcome in irritable bowel syndrome (IBS). Based on the female predominance as well as the correlation between IBS symptoms and hormonal status, several models have been proposed to examine the role of sex hormones in gastrointestinal (GI) function including differences in GI symptoms expression in distinct phases of the menstrual cycle, in pre- and post-menopausal women, during pregnancy, hormonal treatment or after oophorectomy. Sex hormones may influence peripheral and central regulatory mechanisms of the brain-gut axis involved in the pathophysiology of IBS contributing to the alterations in visceral sensitivity, motility, intestinal barrier function, and immune activation of intestinal mucosa. Sex differences in stress response of the hypothalamic-pituitary-adrenal axis and autonomic nervous system, neuroimmune interactions triggered by stress, as well as estrogen interactions with serotonin and corticotropin-releasing factor signaling systems are being increasingly recognized. A concept of "microgenderome" related to the potential role of sex hormone modulation of the gut microbiota is also emerging. Significant differences between IBS female and male patients regarding symptomatology and comorbidity with other chronic pain syndromes and psychiatric disorders, together with differences in efficacy of serotonergic medications in IBS patients confirm the necessity for more sex-tailored therapeutic approach in this disorder.

  7. Can hydroxylamine be a more potent nucleophile for the reactivation of tabun-inhibited AChE than prototype oxime drugs? An answer derived from quantum chemical and steered molecular dynamics studies.

    Science.gov (United States)

    Lo, Rabindranath; Ganguly, Bishwajit

    2014-07-29

    Organophosphorus nerve agents are highly toxic compounds which strongly inhibit acetylcholinesterase (AChE) in the blood and in the central nervous system (CNS). Tabun is one of the highly toxic organophosphorus (OP) compounds and is resistant to many oxime drugs formulated for the reactivation of AChE. The reactivation mechanism of tabun-conjugated AChE with various drugs has been examined with density functional theory and ab initio quantum chemical calculations. The presence of a lone-pair located on the amidic group resists the nucleophilic attack at the phosphorus center of the tabun-conjugated AChE. We have shown that the newly designed drug candidate N-(pyridin-2-yl)hydroxylamine, at the MP2/6-31+G*//M05-2X/6-31G* level in the aqueous phase with the polarizable continuum solvation model (PCM), is more effective in reactivating the tabun-conjugated AChE than typical oxime drugs. The rate determining activation barrier with N-(pyridin-2-yl)hydroxylamine was found to be ∼1.7 kcal mol(-1), which is 7.2 kcal mol(-1) lower than the charged oxime trimedoxime (one of the most efficient reactivators in tabun poisonings). The greater nucleophilicity index (ω(-)) and higher CHelpG charge of pyridinylhydroxylamine compared to TMB4 support this observation. Furthermore, we have also examined the reactivation process of tabun-inhibited AChE with some other bis-quaternary oxime drug candidates such as methoxime (MMB4) and obidoxime. The docking analysis suggests that charged bis-quaternary pyridinium oximes have greater binding affinity inside the active-site gorge of AChE compared to the neutral pyridinylhydroxylamine. The peripheral ligand attached to the neutral pyridinylhydroxylamine enhanced the binding with the aromatic residues in the active-site gorge of AChE through effective π-π interactions. Steered molecular dynamics (SMD) simulations have also been performed with the charged oxime (TMB4) and the neutral hydroxylamine. From protein-drug interaction

  8. Bacterial metabolic 'toxins': a new mechanism for lactose and food intolerance, and irritable bowel syndrome.

    Science.gov (United States)

    Campbell, A K; Matthews, S B; Vassel, N; Cox, C D; Naseem, R; Chaichi, J; Holland, I B; Green, J; Wann, K T

    2010-12-30

    Lactose and food intolerance cause a wide range of gut and systemic symptoms, including gas, gut pain, diarrhoea or constipation, severe headaches, severe fatigue, loss of cognitive functions such as concentration, memory and reasoning, muscle and joint pain, heart palpitations, and a variety of allergies (Matthews and Campbell, 2000; Matthews et al., 2005; Waud et al., 2008). These can be explained by the production of toxic metabolites from gut bacteria, as a result of anaerobic digestion of carbohydrates and other foods, not absorbed in the small intestine. These metabolites include alcohols, diols such as butan 2,3 diol, ketones, acids, and aldehydes such as methylglyoxal (Campbell et al., 2005, 2009). These 'toxins' induce calcium signals in bacteria and affect their growth, thereby acting to modify the balance of microflora in the gut (Campbell et al., 2004, 2007a,b). These bacterial 'toxins' also affect signalling mechanisms in cells around the body, thereby explaining the wide range of symptoms in people with food intolerance. This new mechanism also explains the most common referral to gastroenterologists, irritable bowel syndrome (IBS), and the illness that afflicted Charles Darwin for 50 years (Campbell and Matthews, 2005a,b). We propose it will lead to a new understanding of the molecular mechanism of type 2 diabetes and some cancers. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  9. The mind-body connection in irritable bowel syndrome: A randomised controlled trial of hypnotherapy as a treatment.

    Science.gov (United States)

    Phillips-Moore, Julie S; Talley, Nicholas J; Jones, Michael P

    2015-01-01

    Hypnotherapy has been reported as being beneficial in the treatment of irritable bowel syndrome (IBS). We aimed to test the hypothesis that patients with IBS treated 'holistically' by hypnosis (i.e. by combined psychological and physiological symptom imagery) would have greater improvement in their IBS symptoms than patients treated by hypnosis using standard 'gut-directed' hypnotherapy, and both would be superior to simple relaxation therapy. Patients ( n  = 51) with Rome II criteria were randomised to 'individualised' (holistic) hypnotherapy, standard 'gut-directed' hypnotherapy or relaxation therapy for a period of 11 weeks with two follow-up assessments at 2 weeks and at 3 months after the completion of the trial. The primary outcome was bowel symptom severity scale (BSSS). All the participants in this study improved their IBS symptoms (pain, bloating, constipation and diarrhoea) and physical functioning at the end of the treatment from baseline, but this was not significantly different across the treatment arms. Neither 'individualised' nor 'gut-directed' hypnotherapy is superior to relaxation therapy in IBS.

  10. The mind–body connection in irritable bowel syndrome: A randomised controlled trial of hypnotherapy as a treatment

    Science.gov (United States)

    Talley, Nicholas J; Jones, Michael P

    2015-01-01

    Background: Hypnotherapy has been reported as being beneficial in the treatment of irritable bowel syndrome (IBS). We aimed to test the hypothesis that patients with IBS treated ‘holistically’ by hypnosis (i.e. by combined psychological and physiological symptom imagery) would have greater improvement in their IBS symptoms than patients treated by hypnosis using standard ‘gut-directed’ hypnotherapy, and both would be superior to simple relaxation therapy. Methods: Patients (n = 51) with Rome II criteria were randomised to ‘individualised’ (holistic) hypnotherapy, standard ‘gut-directed’ hypnotherapy or relaxation therapy for a period of 11 weeks with two follow-up assessments at 2 weeks and at 3 months after the completion of the trial. The primary outcome was bowel symptom severity scale (BSSS). Results: All the participants in this study improved their IBS symptoms (pain, bloating, constipation and diarrhoea) and physical functioning at the end of the treatment from baseline, but this was not significantly different across the treatment arms. Conclusion: Neither ‘individualised’ nor ‘gut-directed’ hypnotherapy is superior to relaxation therapy in IBS. PMID:28070348

  11. Acetylcholinesterase Regulates Skeletal In Ovo Development of Chicken Limbs by ACh-Dependent and -Independent Mechanisms.

    Directory of Open Access Journals (Sweden)

    Janine Spieker

    Full Text Available Formation of the vertebrate limb presents an excellent model to analyze a non-neuronal cholinergic system (NNCS. Here, we first analyzed the expression of acetylcholinesterase (AChE by IHC and of choline acetyltransferase (ChAT by ISH in developing embryonic chicken limbs (stages HH17-37. AChE outlined formation of bones, being strongest at their distal tips, and later also marked areas of cell death. At onset, AChE and ChAT were elevated in two organizing centers of the limb anlage, the apical ectodermal ridge (AER and zone of polarizing activity (ZPA, respectively. Thereby ChAT was expressed shortly after AChE, thus strongly supporting a leading role of AChE in limb formation. Then, we conducted loss-of-function studies via unilateral implantation of beads into chicken limb anlagen, which were soaked in cholinergic components. After varying periods, the formation of cartilage matrix and of mineralizing bones was followed by Alcian blue (AB and Alizarin red (AR stainings, respectively. Both acetylcholine (ACh- and ChAT-soaked beads accelerated bone formation in ovo. Notably, inhibition of AChE by BW284c51, or by the monoclonal antibody MAB304 delayed cartilage formation. Since bead inhibition of BChE was mostly ineffective, an ACh-independent action during BW284c51 and MAB304 inhibition was indicated, which possibly could be due to an enzymatic side activity of AChE. In conclusion, skeletogenesis in chick is regulated by an ACh-dependent cholinergic system, but to some extent also by an ACh-independent aspect of the AChE protein.

  12. Prebiotics effect on immune and hepatic oxidative status and gut morphology of white sea bream (Diplodus sargus).

    Science.gov (United States)

    Guerreiro, Inês; Couto, Ana; Machado, Marina; Castro, Carolina; Pousão-Ferreira, Pedro; Oliva-Teles, Aires; Enes, Paula

    2016-03-01

    The aim of this study was to evaluate the effects of short-chain fructooligosaccharides (scFOS), xylooligosaccharides (XOS) and galactooligosaccharides (GOS) on immune and hepatic oxidative status, and gut morphology of white sea bream juveniles. Four diets were formulated: a control diet with fish meal (FM) and plant feedstuffs (PF) (30FM:70PF) and three test diets similar to the control but supplemented with 1% of scFOS, XOS or GOS. Dietary prebiotic incorporation did not affect total blood cell counts, hematocrit, hemoglobin, red blood indices or differential white blood cell counts. Fish fed GOS had lower ACH50 and nitric oxide than fish fed control diet. XOS enhanced immune status through the increase in alternative complement pathway (ACH50), lysozyme and total immunoglobulin. The higher activity of glucose 6-phosphate dehydrogenase in fish fed FOS compared to the other dietary groups was the only related antioxidant enzyme affected by prebiotics in the liver. GOS ameliorated the precocious adverse effects of PF based diet on gut histomorphology, as denoted by the lower incidence of histological alterations in fish fed GOS for 15 days. In conclusion, XOS and GOS at 1% might have potential to be used as prebiotics in white sea bream juveniles. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Neurotransmitters and putative neuromodulators in the gut of Anguilla anguilla (L.. Localizations in the enteric nervous and endocrine systems

    Directory of Open Access Journals (Sweden)

    A Veggetti

    2009-12-01

    Full Text Available The gut of silver eels (Anguilla anguilla L. was investigated in order to describe both the cholinergic and adrenergic intramural innervations, and the localization of possible accessory neuromediators. Histochemical reactions for the demonstration of nicotinamide adenine dinucleotide phosphate, reduced form-(NADPH-diaphorase and acetylcholinesterese (AChEase were performed, as well as the immunohistochemical testing of tyrosine hydroxylase, met-enkephalin, substance P, calcitonin gene-related peptide (CGRP, bombesin, vasoactive intestinal peptide (VIP, neuropeptide Y (NPY, somatostatin, cholecystokinin-octapeptide (CCK-8, serotonin, cholineacetyltransferase. The results evidenced a different pattern in comparison with other vertebrates, namely mammals, and with other fish. Both NADPH-diaphorase and AChEase activities were histochemically detected all along the gut in the myenteric plexus, the inner musculature and the propria-submucosa. Tyrosine hydroxylase immunoreactivity was observed in the intestinal tract only, both in the myenteric plexus and in the inner musculature. Several neuropeptides (metenkephalin, CGRP, bombesin, substance P, VIP, NPY, somatostatin were, in addition, detected in the intramural innervation; some of them also in epithelial cells of the diffuse endocrine system (met-enkephalin, substance P, NPY, somatostatin. Serotonin was only present in endocrine cells. Tyrosine hydroxylase immunoreactivity was present in localizations to those of similar NADPHdiaphorase- reactivity, and in the same nerve bundles in which substance P- and CGRP-likeimmunoreactivities were detectable in the intestinal tract. In addition, NADPH-diaphorase-reactive neurons showed an anatomical relationship with AChEase-reactive nerve terminals, and a similar relationship existed between the latter and substance P-like immunoreactivity.

  14. Home-Based Hypnotherapy Self-exercises vs Individual Hypnotherapy With a Therapist for Treatment of Pediatric Irritable Bowel Syndrome, Functional Abdominal Pain, or Functional Abdominal Pain Syndrome: A Randomized Clinical Trial

    NARCIS (Netherlands)

    Rutten, Juliette M. T. M.; Vlieger, Arine M.; Frankenhuis, Carla; George, Elvira K.; Groeneweg, Michael; Norbruis, Obbe F.; Tjon A ten, Walther; van Wering, Herbert M.; Dijkgraaf, Marcel G. W.; Merkus, Maruschka P.; Benninga, Marc A.

    2017-01-01

    Individual gut-directed hypnotherapy (HT) is effective in pediatric irritable bowel syndrome (IBS) and functional abdominal pain or functional abdominal pain syndrome (FAP[S]). It is, however, unavailable to many children. To compare the effectiveness of HT by means of home-based self-exercises

  15. Dual Inhibition of AChE and BChE with the C-5 Substituted Derivative of Meldrum’s Acid: Synthesis, Structure Elucidation, and Molecular Docking Studies

    Directory of Open Access Journals (Sweden)

    Haroon Mehfooz

    2017-07-01

    Full Text Available Alzheimer’s disease (AD lies in the category of those diseases which are still posing challenges to medicinal chemists, and the search for super-effective drugs for the treatment of AD is a work in progress. The inhibition of cholinesterase is considered a viable strategy to enhance the level of acetylcholine in the brain. The C-5 substituted derivative of Meldrum’s acid was synthesized and screened against acetylcholinesterase (AChE and butyrylcholinesterase (BChE enzyme inhibition activity. The simple and unique structure of synthesized derivative 3 was found to be good for the dual inhibition of both enzymes (AChE and BChE. 2,2-Dimethyl-5-(([2-(trifluoromethyl phenyl]aminomethylidene-1,3-dioxane-4,6-dione (3 showed significant inhibition against AChE, with an IC50 value of 1.13 ± 0.03 µ M (Standard Neostigmine 22.2 ± 3.2 µM, and moderate inhibition against BChE, with an IC50 value of 2.12 ± 1.22 µM (Standard Neostigmine 49.6 ± 6.11 µM. The structural insights reveal that compound 3 possesses intriguing reactive groups, which can potentially evoke the non-covalent interactions and possibly assist by binding in the active site of the target protein. Docking simulations revealed that the compound 3 showed binding inside the active site gorges of both AChE and BChE. An excellent agreement was obtained, as the best docked poses showed important binding features mostly based on interactions due to oxygen atoms and the aromatic moieties of the compound. The docking computations coupled with the experimental findings ascertained that the compound 3 can serve as a scaffold for the dual inhibitors of the human acetylcholine esterases.

  16. MRI of hyperacute stroke in the AChA territory

    Energy Technology Data Exchange (ETDEWEB)

    Hamoir, Xavier L.; Grandin, Cecile B.; Cosnard, Guy; Duprez, Thierry [Department of Medical Imaging, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Avenue Hippocrate 10, 1200, Brussels (Belgium); Peeters, Andre [Department of Neurology, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Avenue Hippocrate 10, 1200, Brussels (Belgium); Robert, Annie [Department of Epidemiology, Biostatistics Unit of the Public Health School, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Avenue Hippocrate 10, 1200, Brussels (Belgium)

    2004-03-01

    The purpose of our study was to derive from the anatomical literature an easy-to-use map of the brain areas supplied by the anterior choroidal artery (AChA) and to assess the correspondence between damage within the putative AChA areas and clinical symptoms. A thorough review of the literature led to the recognition of 16 anatomical areas which could be delineated on routine diffusion-weighted MR images. A database of 138 consecutive ischemic stroke patients examined with MRI less than 6 h after symptoms onset was thereafter processed in a retrospective way. Patients presenting with at least one damaged AChA area were selected so as to assess the prevalence of AChA infarction and the clinical correlates of the condition. Fifteen patients (11%) had at least one damaged AChA area. Only two of them had ''pure'' AChA-restricted infarction. Contralateral hemiparesis and contralateral hemianesthesia were best predicted by lesions within the tail of the caudate nucleus with a sensitivity of 87% and 83%, respectively. Homonymous hemianopsia best correlated with lesions within the posterior limb of the internal capsule and within the retrolenticular part of the internal capsule, with a sensitivity of 100% and a specificity of 70% for both areas. We concluded that the clinical-radiological correlations did not match the neurophysiological standards, thereby highlighting the limitation of this study, which involved a cohort of acute stroke patients recruited from clinical practice and investigated the clinical impact of these brain lesions, even when documented with the most sensitive imaging modality. (orig.)

  17. MRI of hyperacute stroke in the AChA territory

    International Nuclear Information System (INIS)

    Hamoir, Xavier L.; Grandin, Cecile B.; Cosnard, Guy; Duprez, Thierry; Peeters, Andre; Robert, Annie

    2004-01-01

    The purpose of our study was to derive from the anatomical literature an easy-to-use map of the brain areas supplied by the anterior choroidal artery (AChA) and to assess the correspondence between damage within the putative AChA areas and clinical symptoms. A thorough review of the literature led to the recognition of 16 anatomical areas which could be delineated on routine diffusion-weighted MR images. A database of 138 consecutive ischemic stroke patients examined with MRI less than 6 h after symptoms onset was thereafter processed in a retrospective way. Patients presenting with at least one damaged AChA area were selected so as to assess the prevalence of AChA infarction and the clinical correlates of the condition. Fifteen patients (11%) had at least one damaged AChA area. Only two of them had ''pure'' AChA-restricted infarction. Contralateral hemiparesis and contralateral hemianesthesia were best predicted by lesions within the tail of the caudate nucleus with a sensitivity of 87% and 83%, respectively. Homonymous hemianopsia best correlated with lesions within the posterior limb of the internal capsule and within the retrolenticular part of the internal capsule, with a sensitivity of 100% and a specificity of 70% for both areas. We concluded that the clinical-radiological correlations did not match the neurophysiological standards, thereby highlighting the limitation of this study, which involved a cohort of acute stroke patients recruited from clinical practice and investigated the clinical impact of these brain lesions, even when documented with the most sensitive imaging modality. (orig.)

  18. Irritable Bowel Syndrome: Yoga as Remedial Therapy

    Science.gov (United States)

    Kavuri, Vijaya; Raghuram, Nagarathna; Malamud, Ariel; Selvan, Senthamil R.

    2015-01-01

    Irritable bowel syndrome (IBS) is a group of symptoms manifesting as a functional gastrointestinal (GI) disorder in which patients experience abdominal pain, discomfort, and bloating that is often relieved with defecation. IBS is often associated with a host of secondary comorbidities such as anxiety, depression, headaches, and fatigue. In this review, we examined the basic principles of Pancha Kosha (five sheaths of human existence) concept from an Indian scripture Taittiriya Upanishad and the pathophysiology of a disease from the Yoga approach, Yoga Vasistha's Adhi (originated from mind) and Vyadhi (ailment/disease) concept. An analogy between the age old, the most profound concept of Adhi-Vyadhi, and modern scientific stress-induced dysregulation of brain-gut axis, as it relates to IBS that could pave way for impacting IBS, is emphasized. Based on these perspectives, a plausible Yoga module as a remedial therapy is provided to better manage the primary and secondary symptoms of IBS. PMID:26064164

  19. Irritable Bowel Syndrome: Yoga as Remedial Therapy

    Directory of Open Access Journals (Sweden)

    Vijaya Kavuri

    2015-01-01

    Full Text Available Irritable bowel syndrome (IBS is a group of symptoms manifesting as a functional gastrointestinal (GI disorder in which patients experience abdominal pain, discomfort, and bloating that is often relieved with defecation. IBS is often associated with a host of secondary comorbidities such as anxiety, depression, headaches, and fatigue. In this review, we examined the basic principles of Pancha Kosha (five sheaths of human existence concept from an Indian scripture Taittiriya Upanishad and the pathophysiology of a disease from the Yoga approach, Yoga Vasistha’s Adhi (originated from mind and Vyadhi (ailment/disease concept. An analogy between the age old, the most profound concept of Adhi-Vyadhi, and modern scientific stress-induced dysregulation of brain-gut axis, as it relates to IBS that could pave way for impacting IBS, is emphasized. Based on these perspectives, a plausible Yoga module as a remedial therapy is provided to better manage the primary and secondary symptoms of IBS.

  20. Irritancies of shampoos

    Directory of Open Access Journals (Sweden)

    Singh Sanjay

    1991-01-01

    Full Text Available Six commonly used shampoos were tested for their relative irritancies using Kligman and Wooding′s technique. Shampoos in increasing order of irritancies were Halo egg, Aqua dermis, Clinic plus, Sunsilk, Velvette black and Mediker.

  1. Irritable Bowel Syndrome

    Science.gov (United States)

    ... your belly area), constipation (when you can't poop), and diarrhea (when you poop too much). If you have irritable bowel syndrome, ... food particles are also known as stool, a bowel movement, or poop. Here's why an intestine gets "irritable." ...

  2. Comparative functional expression of nAChR subtypes in rodent DRG neurons.

    Science.gov (United States)

    Smith, Nathan J; Hone, Arik J; Memon, Tosifa; Bossi, Simon; Smith, Thomas E; McIntosh, J Michael; Olivera, Baldomero M; Teichert, Russell W

    2013-01-01

    We investigated the functional expression of nicotinic acetylcholine receptors (nAChRs) in heterogeneous populations of dissociated rat and mouse lumbar dorsal root ganglion (DRG) neurons by calcium imaging. By this experimental approach, it is possible to investigate the functional expression of multiple receptor and ion-channel subtypes across more than 100 neuronal and glial cells simultaneously. Based on nAChR expression, DRG neurons could be divided into four subclasses: (1) neurons that express predominantly α3β4 and α6β4 nAChRs; (2) neurons that express predominantly α7 nAChRs; (3) neurons that express a combination of α3β4/α6β4 and α7 nAChRs; and (4) neurons that do not express nAChRs. In this comparative study, the same four neuronal subclasses were observed in mouse and rat DRG. However, the expression frequency differed between species: substantially more rat DRG neurons were in the first three subclasses than mouse DRG neurons, at all developmental time points tested in our study. Approximately 70-80% of rat DRG neurons expressed functional nAChRs, in contrast to only ~15-30% of mouse DRG neurons. Our study also demonstrated functional coupling between nAChRs, voltage-gated calcium channels, and mitochondrial Ca(2) (+) transport in discrete subsets of DRG neurons. In contrast to the expression of nAChRs in DRG neurons, we demonstrated that a subset of non-neuronal DRG cells expressed muscarinic acetylcholine receptors and not nAChRs. The general approach to comparative cellular neurobiology outlined in this paper has the potential to better integrate molecular and systems neuroscience by uncovering the spectrum of neuronal subclasses present in a given cell population and the functionally integrated signaling components expressed in each subclass.

  3. Study on the Highly Sensitive AChE Electrode Based on Multiwalled Carbon Nanotubes

    Directory of Open Access Journals (Sweden)

    Shuping Zhang

    2014-01-01

    Full Text Available Using chitosan (CS as carrier, the method named layer-by-layer (LBL self-assembly modification to modify the glassy carbon electrode (GCE with multiwalled carbon nanotubes (MWNTs and acetylcholine esterase (AChE was proposed to prepare the acetylcholine esterase electrode with high sensitivity and stability. The modified electrode was used to detect pesticide of aldicarb, and the enzyme inhibition rate of the electrode showed good linearity with pesticide concentrations in the range of 10−10 g·L−1 to 10−3 g·L−1. The detection limit was 10−11 g·L−1. The modified electrode was also used to detect the actual sample, and the recovery rate range was from 97.72% to 107.15%, which could meet the rapid testing need of the aldicarb residue. After being stored in the phosphate buffer solution (PBS in 4°C for 30 days, the modified electrode showed good stability with the response current that was 80% of the original current.

  4. The human gut microbiome, a taxonomic conundrum.

    Science.gov (United States)

    Sankar, Senthil Alias; Lagier, Jean-Christophe; Pontarotti, Pierre; Raoult, Didier; Fournier, Pierre-Edouard

    2015-06-01

    From culture to metagenomics, within only 130 years, our knowledge of the human microbiome has considerably improved. With >1000 microbial species identified to date, the gastro-intestinal microbiota is the most complex of human biotas. It is composed of a majority of Bacteroidetes and Firmicutes and, although exhibiting great inter-individual variations according to age, geographic origin, disease or antibiotic uptake, it is stable over time. Metagenomic studies have suggested associations between specific gut microbiota compositions and a variety of diseases, including irritable bowel syndrome, Crohn's disease, colon cancer, type 2 diabetes and obesity. However, these data remain method-dependent, as no consensus strategy has been defined to decipher the complexity of the gut microbiota. High-throughput culture-independent techniques have highlighted the limitations of culture by showing the importance of uncultured species, whereas modern culture methods have demonstrated that metagenomics underestimates the microbial diversity by ignoring minor populations. In this review, we highlight the progress and challenges that pave the way to a complete understanding of the human gastrointestinal microbiota and its influence on human health. Copyright © 2015 Elsevier GmbH. All rights reserved.

  5. Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism

    Science.gov (United States)

    Gao, Jing; Xu, Kang; Liu, Hongnan; Liu, Gang; Bai, Miaomiao; Peng, Can; Li, Tiejun; Yin, Yulong

    2018-01-01

    The gut microbiota influences the health of the host, especially with regard to gut immune homeostasis and the intestinal immune response. In addition to serving as a nutrient enhancer, L-tryptophan (Trp) plays crucial roles in the balance between intestinal immune tolerance and gut microbiota maintenance. Recent discoveries have underscored that changes in the microbiota modulate the host immune system by modulating Trp metabolism. Moreover, Trp, endogenous Trp metabolites (kynurenines, serotonin, and melatonin), and bacterial Trp metabolites (indole, indolic acid, skatole, and tryptamine) have profound effects on gut microbial composition, microbial metabolism, the host's immune system, the host-microbiome interface, and host immune system–intestinal microbiota interactions. The aryl hydrocarbon receptor (AhR) mediates the regulation of intestinal immunity by Trp metabolites (as ligands of AhR), which is beneficial for immune homeostasis. Among Trp metabolites, AhR ligands consist of endogenous metabolites, including kynurenine, kynurenic acid, xanthurenic acid, and cinnabarinic acid, and bacterial metabolites, including indole, indole propionic acid, indole acetic acid, skatole, and tryptamine. Additional factors, such as aging, stress, probiotics, and diseases (spondyloarthritis, irritable bowel syndrome, inflammatory bowel disease, colorectal cancer), which are associated with variability in Trp metabolism, can influence Trp–microbiome–immune system interactions in the gut and also play roles in regulating gut immunity. This review clarifies how the gut microbiota regulates Trp metabolism and identifies the underlying molecular mechanisms of these interactions. Increased mechanistic insight into how the microbiota modulates the intestinal immune system through Trp metabolism may allow for the identification of innovative microbiota-based diagnostics, as well as appropriate nutritional supplementation of Trp to prevent or alleviate intestinal inflammation

  6. The mind–body connection in irritable bowel syndrome: A randomised controlled trial of hypnotherapy as a treatment

    Directory of Open Access Journals (Sweden)

    Julie S Phillips-Moore

    2015-01-01

    Full Text Available Background: Hypnotherapy has been reported as being beneficial in the treatment of irritable bowel syndrome (IBS. We aimed to test the hypothesis that patients with IBS treated ‘holistically’ by hypnosis (i.e. by combined psychological and physiological symptom imagery would have greater improvement in their IBS symptoms than patients treated by hypnosis using standard ‘gut-directed’ hypnotherapy, and both would be superior to simple relaxation therapy. Methods: Patients ( n  = 51 with Rome II criteria were randomised to ‘individualised’ (holistic hypnotherapy, standard ‘gut-directed’ hypnotherapy or relaxation therapy for a period of 11 weeks with two follow-up assessments at 2 weeks and at 3 months after the completion of the trial. The primary outcome was bowel symptom severity scale (BSSS. Results: All the participants in this study improved their IBS symptoms (pain, bloating, constipation and diarrhoea and physical functioning at the end of the treatment from baseline, but this was not significantly different across the treatment arms. Conclusion: Neither ‘individualised’ nor ‘gut-directed’ hypnotherapy is superior to relaxation therapy in IBS.

  7. Prevalence, incidence, and risk factors of intestinal parasites in Danish primary care patients with irritable bowel syndrome

    DEFF Research Database (Denmark)

    Engsbro, Anne Line; Stensvold, Christen Rune; Nielsen, Henrik Vedel

    2014-01-01

    The gut microbiota may be involved in the aetiopathogenesis of irritable bowel syndrome (IBS). We studied the role of intestinal parasites by describing the epidemiology and risk factors for infection in primary care patients aged 18-50 y with IBS. One hundred and thirty-eight patients at baseline...... and 78/116 patients returning 1 y later, submitted faecal samples that were examined by microscopy, culture for Blastocystis, and real-time PCR for Dientamoeba fragilis, Entamoeba (dispar and histolytica), Cryptosporidium spp., and Giardia intestinalis. Overall, 42-45% of patients harboured intestinal...

  8. Surfactant-induced skin irritation and skin repair: evaluation of a cumulative human irritation model by noninvasive techniques.

    Science.gov (United States)

    Wilhelm, K P; Freitag, G; Wolff, H H

    1994-12-01

    Although surfactant-induced acute irritant dermatitis has been extensively studied, our understanding about the induction and repair of the clinically more relevant chronic form is limited. Our purpose was to investigate qualitative and quantitative differences in surfactant-induced irritant skin reactions from cumulative exposure to structurally unrelated surfactants and to compare the maximal irritant responses from this model with corresponding reactions noted in a previously reported acute irritation model. Sodium lauryl sulfate (SLS), dodecyl trimethyl ammonium bromide (DTAB), and potassium soap were the model irritants. Surfactant solutions (7.5%) were applied for 20 minutes daily (for 8 consecutive days excluding the weekend) to the volar aspect of the forearm of 11 volunteers. Irritant reactions were repeatedly assessed until complete healing was indicated by visual assessment and by measurements of transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum corneum hydration (electrical capacitance). Maximum irritant responses were compared with corresponding reactions from an acute irritation model. TEWL was increased by SLS and DTAB to the same extent, but erythema was significantly higher in DTAB-treated skin. Skin dryness, as demonstrated by decreased capacitance values and increased scores for scaling and fissuring, was significantly more pronounced than in an acute irritation model for SLS and DTAB, although no difference was detected between the two surfactants. Potassium soap led to a slight increase in TEWL, whereas the remaining features were not significantly changed. This chronic irritation model appears to represent the clinical situation of irritant contact dermatitis with pronounced skin dryness more closely than the acute irritation model. The present study confirms that an extended time is needed for complete healing of irritant skin reactions. We also demonstrated that the evaluation of the irritation potential of

  9. Eluxadoline in the treatment of diarrhea-predominant irritable bowel syndrome: The SEPD perspective

    Directory of Open Access Journals (Sweden)

    Isabel Vera

    Full Text Available Functional gut disorders, including diarrhea-predominant irritable bowel syndrome, are highly prevalent conditions worldwide that significantly impact health economy and patient quality of life, yet lacking fully satisfactory therapeutic options. These circumstances fostered research on various molecules with more specific therapeutic targets, including opioid receptors. Eluxadoline (Allergan's Vibercy® in the USA, Truberzi® in Europe is a locally-acting mixed µ- and κ-opioid receptor agonist, and δ-opioid receptor antagonist, that was licensed in 2015 by the Food and Drug Administration (FDA and in 2016 by the European Medicines Agency (EMA for use in diarrhea-predominant irritable bowel syndrome. Eluxadoline provides, with advantage over the current standard of care, control of both stool consistency and abdominal pain, good tolerability in most cases, and improved quality of life, hence it deserves consideration when approaching a patient with this disorder. As with any recently approved therapy, adequate pharmacovigilance is to be expected, as well as studies to inform on different scenarios such as on-demand therapy, loss of response assessment, use as rescue therapy for other molecules, and cost-effectiveness, to further characterize and more accurately position eluxadoline within the therapeutic spectrum.

  10. ACh-induced hyperpolarization and decreased resistance in mammalian type II vestibular hair cells.

    Science.gov (United States)

    Poppi, Lauren A; Tabatabaee, Hessam; Drury, Hannah R; Jobling, Phillip; Callister, Robert J; Migliaccio, Americo A; Jordan, Paivi M; Holt, Joseph C; Rabbitt, Richard D; Lim, Rebecca; Brichta, Alan M

    2018-01-01

    In the mammalian vestibular periphery, electrical activation of the efferent vestibular system (EVS) has two effects on afferent activity: 1) it increases background afferent discharge and 2) decreases afferent sensitivity to rotational stimuli. Although the cellular mechanisms underlying these two contrasting afferent responses remain obscure, we postulated that the reduction in afferent sensitivity was attributed, in part, to the activation of α9- containing nicotinic acetylcholine (ACh) receptors (α9*nAChRs) and small-conductance potassium channels (SK) in vestibular type II hair cells, as demonstrated in the peripheral vestibular system of other vertebrates. To test this hypothesis, we examined the effects of the predominant EVS neurotransmitter ACh on vestibular type II hair cells from wild-type (wt) and α9-subunit nAChR knockout (α9 -/- ) mice. Immunostaining for choline acetyltransferase revealed there were no obvious gross morphological differences in the peripheral EVS innervation among any of these strains. ACh application onto wt type II hair cells, at resting potentials, produced a fast inward current followed by a slower outward current, resulting in membrane hyperpolarization and decreased membrane resistance. Hyperpolarization and decreased resistance were due to gating of SK channels. Consistent with activation of α9*nAChRs and SK channels, these ACh-sensitive currents were antagonized by the α9*nAChR blocker strychnine and SK blockers apamin and tamapin. Type II hair cells from α9 -/- mice, however, failed to respond to ACh at all. These results confirm the critical importance of α9nAChRs in efferent modulation of mammalian type II vestibular hair cells. Application of exogenous ACh reduces electrical impedance, thereby decreasing type II hair cell sensitivity. NEW & NOTEWORTHY Expression of α9 nicotinic subunit was crucial for fast cholinergic modulation of mammalian vestibular type II hair cells. These findings show a multifaceted

  11. Enterochromaffin cells of the human gut: sensors for spices and odorants.

    Science.gov (United States)

    Braun, Thomas; Voland, Petra; Kunz, Lars; Prinz, Christian; Gratzl, Manfred

    2007-05-01

    Release of serotonin from mucosal enterochromaffin cells triggered by luminal substances is the key event in the regulation of gut motility and secretion. We were interested to know whether nasal olfactory receptors are also expressed in the human gut mucosa by enterochromaffin cells and whether their ligands and odorants present in spices, fragrances, detergents, and cosmetics cause serotonin release. Receptor expression was studied by the reverse-transcription polymerase chain reaction method in human mucosal enterochromaffin cells isolated by laser microdissection and in a cell line derived from human enterochromaffin cells. Activation of the cells by odorants was investigated by digital fluorescence imaging using the fluorescent Ca(2+) indicator Fluo-4. Serotonin release was measured in culture supernatants by a serotonin enzyme immunoassay and amperometry using carbon fiber microelectrodes placed on single cells. We found expression of 4 olfactory receptors in microdissected human mucosal enterochromaffin cells and in a cell line derived from human enterochromaffin cells. Ca(2+) imaging studies revealed that odorant ligands of the identified olfactory receptors cause Ca(2+) influx, elevation of intracellular free Ca(2+) levels, and, consequently, serotonin release. Our results show that odorants present in the luminal environment of the gut may stimulate serotonin release via olfactory receptors present in human enterochromaffin cells. Serotonin controls both gut motility and secretion and is implicated in pathologic conditions such as vomiting, diarrhea, and irritable bowel syndrome. Thus, olfactory receptors are potential novel targets for the treatment of gastrointestinal diseases and motility disorders.

  12. [Current issues on irritable bowel syndrome: diet and irritable bowel syndrome].

    Science.gov (United States)

    Kim, Jeong Hwan; Sung, In-Kyung

    2014-09-25

    Irritable bowel syndrome (IBS) is one of the most prevalent functional gastrointestinal disorders. It is a multifactorial disorder with its pathogenesis attributed to abnormal gastrointestinal motility, low-grade inflammation, visceral hypersensitivity, communication in the gut-brain axis, and so on. Traditionally, IBS has been treated with diet and lifestyle modification, fiber supplementation, psychological therapy, and pharmacological treatment. Carbohydrates are intermingled with a wide range of regularly consumed food including grains such as rye and wheat, vegetables, fruits, and legumes. Short-chain carbohydrates that are poorly absorbed exert osmotic effects in the intestinal lumen increasing its water volume, and are rapidly fermented by bacteria with consequent gas production. These effects may be the basis for the induction of most of the gastrointestinal symptoms. This has led to the use of lactose-free diets in those with lactose intolerance and of fructose-reduced diets for fructose malabsorption. As all poorly absorbed short-chain carbohydrates have similar and additive effects in the intestine, a concept has been developed to regard them collectively as FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) and to evaluate a dietary approach that restricts them all. Based on the observational and comparative studies, and randomized-controlled trials, FODMAPs have been shown to trigger gastrointestinal symptoms in patients with IBS. Food choice via the low FODMAPs and potentially other dietary strategies is now a realistic and efficacious therapeutic approach for managing symptoms of IBS.

  13. Síndrome de intestino irritable y diverticulosis

    OpenAIRE

    Kestenberg Himelfar, Abraham; Fundación Valle de Lili

    1998-01-01

    Síndrome de intestino irritable (SII)/ ¿Cómo funciona el sistema digestivo?/¿Qué es el síndrome de intestino irritable?/¿Cuáles son los síntomas del síndrome de intestino irritable?/¿Qué causa el síndrome de intestino irritable?/¿Qué papel juega la tensión emocional en el origen del síndrome de intestino irritable?/¿Cómo saber si el problema es síndrome de intestino irritable o si es algo diferente?/¿Cómo se debe tratar el síndrome de intestino irritable?/¿Se deben evitar algunos alimentos?/¿...

  14. Effects of gut-directed hypnotherapy on IBS in different clinical settings-results from two randomized, controlled trials.

    Science.gov (United States)

    Lindfors, Perjohan; Unge, Peter; Arvidsson, Patrik; Nyhlin, Henry; Björnsson, Einar; Abrahamsson, Hasse; Simrén, Magnus

    2012-02-01

    Gut-directed hypnotherapy has been found to be effective in irritable bowel syndrome (IBS). However, randomized, controlled studies are rare and few have been performed outside highly specialized research centers. The objective of this study was to study the effect of gut-directed hypnotherapy in IBS in different clinical settings outside the traditional research units. The study population included IBS patients refractory to standard management. In study 1, patients were randomized to receive gut-directed hypnotherapy (12 sessions, 1 h/week) in psychology private practices or supportive therapy, whereas patients were randomized to receive gut-directed hypnotherapy in a small county hospital or to serve as waiting list controls in study 2. Gastrointestinal symptom severity and quality of life were evaluated at baseline, at 3 months follow-up and after 1 year. We randomized 138 IBS patients refractory to standard management, 90 in study 1 and 48 in study 2. In both the studies, IBS-related symptoms were improved at 3 months in the gut-directed hypnotherapy groups (Phypnotherapy group than in the control group (Phypnotherapy is an effective treatment alternative for patients with refractory IBS, but the effectiveness is lower when the therapy is given outside the highly specialized research centers.

  15. Brain-Gut-Microbe Communication in Health and Disease

    Directory of Open Access Journals (Sweden)

    Sue eGrenham

    2011-12-01

    Full Text Available Bidirectional signalling between the gastrointestinal tract and the brain is regulated at neural, hormonal and immunological levels. This construct is known as the brain-gut axis and is vital for maintaining homeostasis. Bacterial colonisation of the intestine plays a major role in the post-natal development and maturation of the immune and endocrine systems. These processes are key factors underpinning central nervous system (CNS signalling. Recent research advances have seen a tremendous improvement in our understanding of the scale, diversity and importance of the gut microbiome. This has been reflected in the form of a revised nomenclature to the more inclusive brain-gut-enteric microbiota axis and a sustained research effort to establish how communication along this axis contributes to both normal and pathological conditions. In this review, we will briefly discuss the critical components of this axis and the methodological challenges that have been presented in attempts to define what constitutes a normal microbiota and chart its temporal development. Emphasis is placed on the new research narrative that confirms the critical influence of the microbiota on mood and behaviour. Mechanistic insights are provided with examples of both neural and humoral routes through which these effects can be mediated. The evidence supporting a role for the enteric flora in brain-gut axis disorders is explored with the spotlight on the clinical relevance for irritable bowel syndrome (IBS, a stress-related functional gastrointestinal disorder. We also critically evaluate the therapeutic opportunities arising from this research and consider in particular whether targeting the microbiome might represent a valid strategy for the management of CNS disorders and ponder the pitfalls inherent in such an approach. Despite the considerable challenges that lie ahead, this is an exciting area of research and one that is destined to remain the centre of focus for some

  16. Cumulative irritancy in the guinea pig from low grade irritant vehicles and the angry skin syndrome

    DEFF Research Database (Denmark)

    Andersen, Klaus Ejner; Maibach, H I

    1980-01-01

    A 4-week open cumulative irritancy test in guinea pigs discriminated between two low grade irritant vehicles, nonionic base (anhydrous) and hydrophilic ointment. The procedure might be useful as a predictive test for low grade irritants. The angry skin syndrome was established in the guinea pigs...

  17. [Women's approach to childhood toothache, abdominal ache and earache].

    Science.gov (United States)

    Efe, Emine; Öncel, Selma; Yilmaz, Mualla

    2012-01-01

    This study was conducted to determine women's about attitudes child's teeth, abdomen and ear ache. Those who had lived in Antalya that 6 number primary health care center between March-May 2004 were enrolled in the study. As data collecting tools. A questionnaire prepared by the authors. This study was determined that 29.2 % of the mothers carried out mixture who had prepared at home to child's abdomen and foot base; 30.3 % were to put breast milk childs' ear; 38.9 % were placed aspirin, salt and salts of lemon to childs' teeth ache. The majority of the women make a wrong practices child that teeth, abdomen and ear ache. This traditional practice effecting factors were the women's educational status and age. The results of the study that education about child care, common health problems and incorrect applications shoud be given to women by nurse.

  18. [Differentiation Study of Chinese Medical Syndrome Typing for Diarrhea-predominant Irritable Bowel Syndrome Based on Information of Four Chinese Medical Diagnostic Methods and Brain-gut Peptides].

    Science.gov (United States)

    Wu, Hao-meng; Xu, Zhi-wei; Ao, Hai-qing; Shi, Ya-fei; Hu, Hai-yan; Ji, Yun-peng

    2015-10-01

    To establish discriminant functions of diarrhea-predominant irritable bowel syndrome (IBS-D) by studying it from quantitative diagnosis angle, hoping to reduce interference of subjective factors in diagnosing and differentially diagnosing Chinese medical syndromes of IBS-D. A Chinese medical clinical epidemiological survey was carried out in 439 IBS-D patients using Clinical Information Collection Table of IBS. Initial syndromes were obtained by cluster analysis. They were analyzed using step-by-step discrimination by taking information of four Chinese medical diagnostic methods and serum brain-gut peptides (BGP) as variables. Clustering results were Gan stagnation Pi deficiency syndrome (GSPDS), Pi-Wei weakness syndrome (PWWS), Gan stagnation qi stasis syndrome (GSQSS), Pi-Shen yang deficiency syndrome (PSYDS), Pi-Wei damp-heat syndrome (PWDHS), cold-damp disturbing Pi syndrome (CDDPS). Of them, GSPDS was mostly often seen with effective percentage of 34. 2%, while CDDPS was the least often seen with effective percentage of 5.5%. A total of 5 discriminant functions for GSPDS, PWWS, GSQSS, PSYDS, and PWDHS were obtained by step-by-step dis- crimination method. The retrospective misjudgment rate was 4.1% (16/390), while the cross-validation misjudgment rate was 15.4% (60/390). The establishment of discriminant functions is of value in objectively diagnosing and differentially diagnosing Chinese medical syndromes of IBS-D.

  19. Profile of rifaximin and its potential in the treatment of irritable bowel syndrome

    Directory of Open Access Journals (Sweden)

    Iorio N

    2015-06-01

    Full Text Available Natalya Iorio, Zubair Malik, Ron Schey Section of Gastroenterology, Department of Medicine, Temple University Hospital, Philadelphia, PA, USA Abstract: Irritable bowel syndrome (IBS is a chronic functional gastrointestinal disorder characterized by recurrent abdominal pain and abnormal bowel patterns. Alteration in gut flora, visceral hypersensitivity, and abnormal bowel motility are among numerous factors in the complex pathophysiology of IBS. Antibiotics have been used adjunctively to treat IBS for many years but are associated with various systemic side effects. Rifaximin is a nonabsorbable, broad-spectrum antimicrobial that inhibits bacterial RNA synthesis by binding the β-subunit of microbial RNA polymerase. It targets the gastrointestinal tract and works by reducing the quantity of gas-producing bacteria and altering the predominant species of bacteria present. In vivo animal studies suggest additional beneficial mechanisms of rifaximin, including reducing mucosal inflammation and visceral hypersensitivity. Clinical studies have demonstrated that rifaximin improves symptoms associated with IBS, such as bloating, flatulence, stool consistency, and abdominal pain, and has a side-effect profile similar to placebo. Although additional investigation into optimal dosing, treatment duration, and potential resistance is required, rifaximin presents as a safe and beneficial addition to the current management options for IBS. Keywords: irritable bowel syndrome, rifaximin, small intestinal bacterial overgrowth, mucosal inflammation

  20. Relationship between calcium entry and ACh release in K+ -stimulated rat brain synaptosomes

    International Nuclear Information System (INIS)

    Suszkiw, J.B.; O'Leary, M.E.; Toth, G.P.

    1986-01-01

    This paper examines the pattern of Ca ++ entry-dependent ACh release in relation to the kinetics of Ca ++ entry, and its inactivation in rat brain synaptosomes exposed to 50 mM K 0 + for short and prolonged durations. Intrasynaptosomal ACh was radiolabeled from tritium-choline in the presence of 20 um Paraoxon to inhibit the acetylcholinesterase activity. The release of tritium-ACh was studied in superfused synaptosomal beds formed on glass microfiber filters and by rapid filtration. The intermittent stimulation of superfused synaptosomal beds by 3-min pulses of 50 mM K + evoked decremental output of tritium-ACh which reached nearly undetectable levels after the fifth stimulus

  1. 31 CFR 363.38 - What happens if my financial institution returns an ACH debit?

    Science.gov (United States)

    2010-07-01

    ... TreasuryDirect § 363.38 What happens if my financial institution returns an ACH debit? If your designated financial institution returns an ACH debit, we reserve the right to reinitiate the debit at our option. We.... We are not responsible for any fees your financial institution may charge relating to returned ACH...

  2. Surfactant-induced skin irritation and skin repair. Evaluation of the acute human irritation model by noninvasive techniques.

    Science.gov (United States)

    Wilhelm, K P; Freitag, G; Wolff, H H

    1994-06-01

    Although the induction of irritant dermatitis by surfactants has been extensively studied in recent years, our understanding of the repair phase of irritant dermatitis is limited. We investigated qualitative and quantitative differences in surfactant-induced irritant skin reactions from short-term exposure to three structurally different surfactants. Sodium lauryl sulfate (SLS), dodecyl trimethyl ammonium bromide (DTAB), and potassium soap were the model irritants. Surfactant solutions (0.5%) were applied for 24 hours to the volar aspect of the forearm of 11 volunteers. Irritant reactions were assessed until complete healing was indicated by visual assessment and by various aspects of skin function, that is, transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum that is, transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum corneum hydration (electrical capacitance). SLS and DTAB induced similar degrees of erythema, whereas SLS induced significantly higher TEWL increase. Although both erythema and TEWL were highest 1 hour after exposure to surfactants, skin dryness was a symptom with delayed onset, justifying the long observation period in this study. Minimum hydration values were measured as late as 7 days after surfactant exposure. Dryness was significantly more pronounced in areas exposed to SLS than in areas exposed to DTAB. Complete repair of the irritant reaction induced by either SLS or DTAB was achieved 17 days after surfactant exposure. Stratum corneum hydration was the last feature to return to baseline values. Potassium soap did not significantly influence any skin function. We emphasize the importance of extended periods needed before a patient with irritant contact dermatitis can be reexposed to irritant substances. The evaluation of the irritation potential of diverse surfactants depended significantly on the feature (erythema vs hydration and TEWL) measured.

  3. Crystal structures of Lymnaea stagnalis AChBP in complex with neonicotinoid insecticides imidacloprid and clothianidin.

    Science.gov (United States)

    Ihara, Makoto; Okajima, Toshihide; Yamashita, Atsuko; Oda, Takuma; Hirata, Koichi; Nishiwaki, Hisashi; Morimoto, Takako; Akamatsu, Miki; Ashikawa, Yuji; Kuroda, Shun'ichi; Mega, Ryosuke; Kuramitsu, Seiki; Sattelle, David B; Matsuda, Kazuhiko

    2008-06-01

    Neonicotinoid insecticides, which act on nicotinic acetylcholine receptors (nAChRs) in a variety of ways, have extremely low mammalian toxicity, yet the molecular basis of such actions is poorly understood. To elucidate the molecular basis for nAChR-neonicotinoid interactions, a surrogate protein, acetylcholine binding protein from Lymnaea stagnalis (Ls-AChBP) was crystallized in complex with neonicotinoid insecticides imidacloprid (IMI) or clothianidin (CTD). The crystal structures suggested that the guanidine moiety of IMI and CTD stacks with Tyr185, while the nitro group of IMI but not of CTD makes a hydrogen bond with Gln55. IMI showed higher binding affinity for Ls-AChBP than that of CTD, consistent with weaker CH-pi interactions in the Ls-AChBP-CTD complex than in the Ls-AChBP-IMI complex and the lack of the nitro group-Gln55 hydrogen bond in CTD. Yet, the NH at position 1 of CTD makes a hydrogen bond with the backbone carbonyl of Trp143, offering an explanation for the diverse actions of neonicotinoids on nAChRs.

  4. Irritability and Anxiety Severity Among Youth With Anxiety

    Science.gov (United States)

    Cornacchio, Danielle; Crum, Kathleen I.; Coxe, Stefany; Pincus, Donna B.; Comer, Jonathan S.

    2015-01-01

    Objective Most research on irritability and child psychopathology has focused on depressive disorders, bipolar disorder, and/or oppositional defiant disorder (ODD). Less is known about relationships between child anxiety and irritability and moderators of such associations. Method Structural equation modeling (SEM) examined associations between anxiety severity and irritability in a large sample of treatment-seeking youth with anxiety disorders (N=663, ages 7–19 years, M=12.25), after accounting for comorbid depressive disorders and ODD. Additional analyses examined whether associations were moderated by child gender, age, and generalized anxiety disorder (GAD) status. Results There was a direct link between child anxiety and irritability even after accounting for comorbid depressive disorders and ODD. Links between child anxiety and irritability were robust across child gender and age. Further, relationships between child anxiety and irritability were comparable across youth with and without GAD, suggesting that the anxiety–irritability link is relevant across child anxiety disorders and not circumscribed to youth with GAD. Conclusion Findings add to an increasing body of evidence linking child irritability to a range of internalizing and externalizing psychopathologies, and suggest that child anxiety assessment should systematically incorporate irritability evaluations. Further, youth in clinical settings displaying irritability should be assessed for the presence of anxiety. Moreover, treatments for childhood anxiety may do well to incorporate new treatment modules as needed that specifically target problems of irritability. PMID:26703910

  5. Gut-Brain Interactions in Inflammatory Bowel Disease: A Clinician’s Perspective

    Directory of Open Access Journals (Sweden)

    Theodore M Bayless

    1995-01-01

    Full Text Available While most physicians and some patients consider psychosocial factors important in aggravating already existing inflammatory bowel disease (IBD, most of the information is based on a few recent scientific studies, varied anecdotal observations and a tendency for patients and some physicians to view psychosocial and stress-related issues with speculation, bias and some stigmatization. Patients with proctitis who have experienced recrudescence of mucosal friability and rectal bleeding within a day of a severe life stress provide a dramatic example of such anecdotes. Time-lag studies have indicated that stress, especially major life events, precedes illness aggravation in patients with IBD but that stress is not disease-specific. The symptoms studied, pain and diarrhea, were more likely to be physiological responses to acute stress rather than reflections of increased disease activity. Current scientific research supposes the prospect that environmental factors influence disease susceptibility through the central nervous system. Stress is associated with alterations in both humoral and cellular immune mechanisms in humans and in experimental animals. While psychosocial factors may not initiate inflammation in IBD, it is possible that they lead to alterations in the immune response and thereby alter disease activity. Mind-gut interactions affect salivation, gastric secretion, gastric motility and colonic motility, as well as numerous other gastrointestinal functions. These ‘physiological’ responses are expected in the IBD patient and perhaps will be accentuated by inflammation and its multiple effects on gut function. Because 10 to 13% of the general population have a tendency to suffer from irritable bowel syndrome (IBS, it is expected that the same percentage of IBD patients will have both IBD and IBS. An example of clinically relevant alterations in pathophysiology is the association of acute proctosigmoiditis with an increase in IBS symptoms

  6. Ultramicromorphological observation of Usnea longissima Ach ...

    African Journals Online (AJOL)

    The Usnea longissima Ach. grew as an epiphyte on Abies georgei and was collected at an altitude of 3640 m above sea level from the Pudacuo National Park in the Shangri-La County of the Diqing Tibetan Autonomous Prefecture in the Yunnan Province of China. Scanning electron microscopy revealed the ...

  7. Gut Microbiota: Modulate its Complexity to Restore the Balance

    Directory of Open Access Journals (Sweden)

    Fermín Mearin

    2015-12-01

    Full Text Available The importance of the gut microbiota to health is becoming more widely appreciated. The range of commensal microorganisms in healthy individuals and in patients with a variety of digestive diseases is under active investigation, and evidence is accumulating to suggest that both the diversity and balance of bacterial species are important for health. Disturbance of the balance of microorganisms – dysbiosis – is associated with obesity and a variety of diseases. Restoring the balance by modulating the microbiota through diet, probiotics, or drugs is now being developed as a potential treatment for digestive diseases. Rifaximin has been shown to increase levels of beneficial bacterial species without perturbing the overall composition of the microbiota in patients with a variety of digestive diseases, making it a ‘eubiotic’ rather than an antibiotic. Rifaximin has demonstrated clinical benefit in the treatment of symptomatic uncomplicated diverticular disease, where changes in the colonic microbiota contribute to the pathogenesis of this disease. Modulating the microbiota is also a promising treatment for some types of irritable bowel syndrome (IBS that have been linked to an overgrowth of coliform and Aeromonas species in the small intestine. Rifaximin has demonstrated efficacy in relieving symptoms and reducing relapses in diarrhoeal IBS in the TARGET-1, 2, and 3 trials, without reducing microbial diversity or increasing antimicrobial resistance. While many aspects of the balance of gut microbiota in disease are not yet fully understood, the new understanding of rifaximin as a modulator of gut microbiota may open up new treatment options in digestive disease.

  8. Gut

    DEFF Research Database (Denmark)

    Muscogiuri, Giovanna; Balercia, Giancarlo; Barrea, Luigi

    2017-01-01

    The gut regulates glucose and energy homeostasis; thus, the presence of ingested nutrients into the gut activates sensing mechanisms that affect both glucose homeostasis and regulate food intake. Increasing evidence suggest that gut may also play a key role in the pathogenesis of type 2 diabetes...... which may be related to both the intestinal microbiological profile and patterns of gut hormones secretion. Intestinal microbiota includes trillions of microorganisms but its composition and function may be adversely affected in type 2 diabetes. The intestinal microbiota may be responsible...... metabolism. Thus, the aim of this manuscript is to review the current evidence on the role of the gut in the pathogenesis of type 2 diabetes, taking into account both hormonal and microbiological aspects....

  9. Pharmacological and immunochemical characterization of α2* nicotinic acetylcholine receptors (nAChRs) in mouse brain

    Science.gov (United States)

    Whiteaker, Paul; Wilking, Jennifer A; Brown, Robert WB; Brennan, Robert J; Collins, Allan C; Lindstrom, Jon M; Boulter, Jim

    2009-01-01

    Aim: α2 nAChR subunit mRNA expression in mice is most intense in the olfactory bulbs and interpeduncular nucleus. We aimed to investigate the properties of α2* nAChRs in these mouse brain regions. Methods: α2 nAChR subunit-null mutant mice were engineered. Pharmacological and immunoprecipitation studies were used to determine the composition of α2 subunit-containing (α2*) nAChRs in these two regions. Results: [125I]Epibatidine (200 pmol/L) autoradiography and saturation binding demonstrated that α2 deletion reduces nAChR expression in both olfactory bulbs and interpeduncular nucleus (by 4.8±1.7 and 92±26 fmol̇mg-1 protein, respectively). Pharmacological characterization using the β2-selective drug A85380 to inhibit [125I]epibatidine binding proved inconclusive, so immunoprecipitation methods were used to further characterize α2* nAChRs. Protocols were established to immunoprecipitate β2 and β4 nAChRs. Immunoprecipitation specificity was ascertained using tissue from β2- and β4-null mutant mice, and efficacy was good (>90% of β2* and >80% of β4* nAChRs were routinely recovered). Conclusion: Immunoprecipitation experiments indicated that interpeduncular nucleus α2* nAChRs predominantly contain β2 subunits, while those in olfactory bulbs contain mainly β4 subunits. In addition, the immunoprecipitation evidence indicated that both nuclei, but especially the interpeduncular nucleus, express nAChR complexes containing both β2 and β4 subunits. PMID:19498420

  10. Biochemical effects of glyphosate based herbicide, Excel Mera 71 on enzyme activities of acetylcholinesterase (AChE), lipid peroxidation (LPO), catalase (CAT), glutathione-S-transferase (GST) and protein content on teleostean fishes.

    Science.gov (United States)

    Samanta, Palas; Pal, Sandipan; Mukherjee, Aloke Kumar; Ghosh, Apurba Ratan

    2014-09-01

    Effects of glyphosate based herbicide, Excel Mera 71 at a dose of 17.20mg/l on enzyme activities of acetylcholinesterase (AChE), lipid peroxidation (LPO), catalase (CAT), glutathione-S-transferase (GST) and protein content were measured in different tissues of two Indian air-breathing teleosts, Anabas testudineus (Bloch) and Heteropneustes fossilis (Bloch) during an exposure period of 30 days under laboratory condition. AChE activity was significantly increased in all the investigated tissues of both fish species and maximum elevation was observed in brain of H. fossilis, while spinal cord of A. testudineus showed minimum increment. Fishes showed significant increase LPO levels in all the tissues; highest was observed in gill of A. testudineus but lowest LPO level was observed in muscle of H. fossilis. CAT was also enhanced in both the fishes, while GST activity in liver diminished substantially and minimum was observed in liver of A. testudineus. Total protein content showed decreased value in all the tissues, maximum reduction was observed in liver and minimum in brain of A. testudineus and H. fossilis respectively. The results indicated that Excel Mera 71 caused serious alterations in the enzyme activities resulting into severe deterioration of fish health; so, AChE, LPO, CAT and GST can be used as suitable indicators of herbicidal toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Irritant Contact Dermatitis : Diagnosis and Risk Factors

    NARCIS (Netherlands)

    Schuttelaar, Maria; Johansen, Jeanne Duus; Lepoittevin, Jean-Pierre; Thyssen, Jacob P.

    2016-01-01

    Irritant contact dermatitis is frequent and is induced by direct and repeated contact with skin irritants such as detergents, abrasives, solvents and physical factors such as dry air and occlusion (by wearing gloves) but also water. When dermatitis has developed, even a minimal skin irritation, like

  12. Optogenetic release of ACh induces rhythmic bursts of perisomatic IPSCs in hippocampus.

    Directory of Open Access Journals (Sweden)

    Daniel A Nagode

    Full Text Available Acetylcholine (ACh influences a vast array of phenomena in cortical systems. It alters many ionic conductances and neuronal firing behavior, often by regulating membrane potential oscillations in populations of cells. Synaptic inhibition has crucial roles in many forms of oscillation, and cholinergic mechanisms regulate both oscillations and synaptic inhibition. In vitro investigations using bath-application of cholinergic receptor agonists, or bulk tissue electrical stimulation to release endogenous ACh, have led to insights into cholinergic function, but questions remain because of the relative lack of selectivity of these forms of stimulation. To investigate the effects of selective release of ACh on interneurons and oscillations, we used an optogenetic approach in which the light-sensitive non-selective cation channel, Channelrhodopsin2 (ChR2, was virally delivered to cholinergic projection neurons in the medial septum/diagonal band of Broca (MS/DBB of adult mice expressing Cre-recombinase under the control of the choline-acetyltransferase (ChAT promoter. Acute hippocampal slices obtained from these animals weeks later revealed ChR2 expression in cholinergic axons. Brief trains of blue light pulses delivered to untreated slices initiated bursts of ACh-evoked, inhibitory post-synaptic currents (L-IPSCs in CA1 pyramidal cells that lasted for 10's of seconds after the light stimulation ceased. L-IPSC occurred more reliably in slices treated with eserine and a very low concentration of 4-AP, which were therefore used in most experiments. The rhythmic, L-IPSCs were driven primarily by muscarinic ACh receptors (mAChRs, and could be suppressed by endocannabinoid release from pyramidal cells. Finally, low-frequency oscillations (LFOs of local field potentials (LFPs were significantly cross-correlated with the L-IPSCs, and reversal of the LFPs near s. pyramidale confirmed that the LFPs were driven by perisomatic inhibition. This optogenetic approach

  13. Regulation of ACh release from guinea pig bladder urothelial cells: potential role in bladder filling sensations.

    Science.gov (United States)

    McLatchie, L M; Young, J S; Fry, C H

    2014-07-01

    The aim of this study was to quantify and characterize the mechanism of non-neuronal ACh release from bladder urothelial cells and to determine if urothelial cells could be a site of action of anti-muscarinic drugs. A novel technique was developed whereby ACh could be measured from freshly isolated guinea pig urothelial cells in suspension following mechanical stimulation. Various agents were used to manipulate possible ACh release pathways in turn and to study the effects of muscarinic receptor activation and inhibition on urothelial ATP release. Minimal mechanical stimulus achieved full ACh release, indicating a small dynamic range and possible all-or-none signal. ACh release involved a mechanism dependent on the anion channel CFTR and intracellular calcium concentration, but was independent of extracellular calcium, vesicular trafficking, connexins or pannexins, organic cation transporters and was not affected by botulinum-A toxin. Stimulating ACh receptors increased ATP production and antagonizing them reduced ATP release, suggesting a link between ACh and ATP release. These results suggest that release of non-neuronal ACh from the urothelium is large enough and well located to act as a modulator of ATP release. It is hypothesized that this pathway may contribute to the actions of anti-muscarinic drugs in reducing the symptoms of lower urinary tract syndromes. Additionally the involvement of CFTR in ACh release suggests an exciting new direction for the treatment of these conditions. © 2014 The British Pharmacological Society.

  14. The Role of Mast Cells in Irritable Bowel Syndrome

    Directory of Open Access Journals (Sweden)

    Kang Nyeong Lee

    2016-01-01

    Full Text Available Irritable bowel syndrome (IBS is one of the most common functional gastrointestinal disorders, but its treatment is unsatisfactory as its pathophysiology is multifactorial. The putative factors of IBS pathophysiology are visceral hypersensitivity and intestinal dysmotility, also including psychological factors, dysregulated gut-brain axis, intestinal microbiota alterations, impaired intestinal permeability, and mucosal immune alterations. Recently, mucosal immune alterations have received much attention with the role of mast cells in IBS. Mast cells are abundant in the intestines and function as intestinal gatekeepers at the interface between the luminal environment in the intestine and the internal milieu under the intestinal epithelium. As a gatekeeper at the interface, mast cells communicate with the adjacent cells such as epithelial, neuronal, and other immune cells throughout the mediators released when they themselves are activated. Many studies have suggested that mast cells play a role in the pathophysiology of IBS. This review will focus on studies of the role of mast cell in IBS and the limitations of studies and will also consider future directions.

  15. Irritable bowel syndrome and visceral hypersensitivity : risk factors and pathophysiological mechanisms.

    Science.gov (United States)

    Deiteren, A; de Wit, A; van der Linden, L; De Man, J G; Pelckmans, P A; De Winter, B Y

    2016-03-01

    Irritable bowel syndrome (IBS) is a common functional gastro-intestinal disorder, characterized by abdominal pain and altered intestinal motility. Visceral hypersensitivity is an important hallmark feature of IBS and is believed to underlie abdominal pain in patients with IBS. The two main risk factors associated with the development of IBS are gastrointestinal inflammation and psychological distress. On a peripheral level, visceral sensitivity seems to be modulated by several mechanisms. Immune cells in the mucosal wall, such as mast cells, and enterochromaffin cells may sensitize afferent nerves by release of their mediators. Furthermore, increased mucosal permeability, altered intestinal microflora and dietary habits may contribute to this feature. On a central level, an increased prevalence of psychiatric comorbidities is demonstrated in IBS patients, alongside alterations in the hormonal brain-gut axis, increased vigilance towards intestinal stimuli and functional and structural changes in the brain. The pathogenesis of IBS is complicated and multifactorial and the treatment remains clinically challenging. Dietary measures and symptomatic control are the cornerstones for IBS treatment and may be sufficient for patients experiencing mild symptoms, alongside education, reassurance and an effective therapeutic physician-patient relationship. New pharmacological therapies are aimed at interfering with mediator release and/or blockade of the relevant receptors within the gut wall, while modulation of the intestinal flora and diet may also be of therapeutic benefit. Tricyclic anti-depressants and serotonin reuptake inhibitors act both on a central and peripheral level by modulating pain signalling pathways. © Acta Gastro-Enterologica Belgica.

  16. The evaluation of the local tolerance of vaginal formulations containing dapivirine using the Slug Mucosal Irritation test and the rabbit vaginal irritation test.

    Science.gov (United States)

    Dhondt, Marijke M M; Adriaens, Els; Roey, Jens Van; Remon, Jean Paul

    2005-08-01

    The purpose of this study was to evaluate the local tolerance of vaginal gels (three gels containing dapivirine, the placebo gel, and Conceptrol) with the Slug Mucosal Irritation test and to compare the results with those of the rabbit vaginal irritation test. The irritation potential on the slug mucosa was assessed by the mucus production caused by a repeated treatment for 5 successive days. Additionally, membrane damage was estimated by the protein and enzyme release. By means of a classification prediction model the formulations were classified into four irritation classes. The effect of a 10-day intravaginal application of the gels on the rabbit vaginal and cervical mucosa was evaluated by means of macroscopic and microscopic examination. The placebo and dapivirine gels induced no irritation of the slug mucosa (low mucus production and protein release, no enzyme release) and no vaginal or cervical irritation in rabbits. Conceptrol caused severe irritation of the slug mucosa (increased mucus production, protein release, and enzyme release) and irritation of the rabbit vagina and cervix. The results obtained with the Slug Mucosal Irritation test were comparable to those of the rabbit vaginal irritation test.

  17. Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options.

    Science.gov (United States)

    Konturek, Peter C; Brzozowski, T; Konturek, S J

    2011-12-01

    Stress, which is defined as an acute threat to homeostasis, shows both short- and long-term effects on the functions of the gastrointestinal tract. Exposure to stress results in alterations of the brain-gut interactions ("brain-gut axis") ultimately leading to the development of a broad array of gastrointestinal disorders including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and other functional gastrointestinal diseases, food antigen-related adverse responses, peptic ulcer and gastroesophageal reflux disease (GERD). The major effects of stress on gut physiology include: 1) alterations in gastrointestinal motility; 2) increase in visceral perception; 3) changes in gastrointestinal secretion; 4) increase in intestinal permeability; 5) negative effects on regenerative capacity of gastrointestinal mucosa and mucosal blood flow; and 6) negative effects on intestinal microbiota. Mast cells (MC) are important effectors of brain-gut axis that translate the stress signals into the release of a wide range of neurotransmitters and proinflammatory cytokines, which may profoundly affect the gastrointestinal physiology. IBS represents the most important gastrointestinal disorder in humans, and is characterized by chronic or recurrent pain associated with altered bowel motility. The diagnostic testing for IBS patients include routine blood tests, stool tests, celiac disease serology, abdominal sonography, breath testing to rule out carbohydrate (lactose, fructose, etc.) intolerance and small intestinal bacterial overgrowth. Colonoscopy is recommended if alarming symptoms are present or to obtain colonic biopsies especially in patients with diarrhoea predominant IBS. The management of IBS is based on a multifactorial approach and includes pharmacotherapy targeted against the predominant symptom, behavioural and psychological treatment, dietary alterations, education, reassurance and effective patient-physician relationship. When evaluating for the stress

  18. Acupuncture-moxibustion in treating irritable bowel syndrome: how does it work?

    Science.gov (United States)

    Ma, Xiao-Peng; Hong, Jue; An, Cai-Ping; Zhang, Dan; Huang, Yan; Wu, Huan-Gan; Zhang, Cui-Hong; Meeuwsen, Sian

    2014-05-28

    Irritable bowel syndrome (IBS) is a functional intestinal disease characterized by abdominal pain or discomfort and altered bowel habits. It has drawn great attention because of its high prevalence, reoccurring symptoms, and severe influence on patients' lives. Many clinical studies have demonstrated the efficacy of acupuncture-moxibustion in treating IBS. Increasing attention has been paid to research regarding the action mechanisms of acupuncture-moxibustion for IBS, and the adoption of modern techniques has achieved some progress. This article reviews the latest advances among action mechanism studies from the perspectives of gastrointestinal motility, visceral hypersensitivity, the brain-gut axis, the neuroendocrine system, and the immune system. It is shown that acupuncture-moxibustion can effectively regulate the above items, and thus, this treatment should have a high efficacy in the treatment of IBS. This article also identifies existing problems in current mechanism research and raises several ideas for future studies. Further revelations regarding these action mechanisms will promote the application of acupuncture-moxibustion in treating IBS.

  19. Identification and Expression of Acetylcholinesterase in Octopus vulgaris Arm Development and Regeneration: a Conserved Role for ACHE?

    Science.gov (United States)

    Fossati, Sara Maria; Candiani, Simona; Nödl, Marie-Therese; Maragliano, Luca; Pennuto, Maria; Domingues, Pedro; Benfenati, Fabio; Pestarino, Mario; Zullo, Letizia

    2015-08-01

    Acetylcholinesterase (ACHE) is a glycoprotein with a key role in terminating synaptic transmission in cholinergic neurons of both vertebrates and invertebrates. ACHE is also involved in the regulation of cell growth and morphogenesis during embryogenesis and regeneration acting through its non-cholinergic sites. The mollusk Octopus vulgaris provides a powerful model for investigating the mechanisms underlying tissue morphogenesis due to its high regenerative power. Here, we performed a comparative investigation of arm morphogenesis during adult arm regeneration and embryonic arm development which may provide insights on the conserved ACHE pathways. In this study, we cloned and characterized O. vulgaris ACHE, finding a single highly conserved ACHE hydrophobic variant, characterized by prototypical catalytic sites and a putative consensus region for a glycosylphosphatidylinositol (GPI)-anchor attachment at the COOH-terminus. We then show that its expression level is correlated to the stage of morphogenesis in both adult and embryonic arm. In particular, ACHE is localized in typical neuronal sites when adult-like arm morphology is established and in differentiating cell locations during the early stages of arm morphogenesis. This possibility is also supported by the presence in the ACHE sequence and model structure of both cholinergic and non-cholinergic sites. This study provides insights into ACHE conserved roles during processes of arm morphogenesis. In addition, our modeling study offers a solid basis for predicting the interaction of the ACHE domains with pharmacological blockers for in vivo investigations. We therefore suggest ACHE as a target for the regulation of tissue morphogenesis.

  20. Probiotics and Irritable Bowel Syndrome

    Directory of Open Access Journals (Sweden)

    Riitta Korpela

    2012-06-01

    Full Text Available Background: Irritable bowel syndrome (IBS is a major cause of abdominal discomfort and gut dysfunction worldwide. It is a poorly understood functional gastrointestinal disorder for which no effective medication is available. It is a benign condition, but its social and economic burden is significant. The symptoms consist of abdominal pain, bloating, flatulence, and irregular bowel movements. Alterations in the intestinal microbiota and mucosal inflammation may contribute to the development of IBS and probiotics could thus relieve the symptoms. This review gives an overview on the existing data on the effects of probiotics on the gastrointestinal symptoms of IBS. Methods: A PUBMED search was made to review the relevant literature, and additional studies were obtained from the references of the selected articles. Results: Clinical trials suggest that certain probiotics or combinations of bacteria have beneficial effects on the IBS symptoms. However the heterogeneity of studies, e.g. suboptimal study design, inadequate number of subjects, different doses and vehicles, inadequate length, make it difficult to compare the differences between probiotics and the effect may be strain-specific. Conclusions: Though evidence is very promising, no general recommendations on the use of probiotics in IBS can be given yet. Further clinical trials and data on the mechanisms of action are needed. Probiotics are considered safe and if future scientific data is able to substantiate their efficacy in IBS, they certainly could be a treatment option in relieving the symptoms in IBS.

  1. [Correlation of the microbiota and intestinal mucosa in the pathophysiology and treatment of irritable bowel, irritable eye, and irritable mind syndrome].

    Science.gov (United States)

    Fehér, János; Kovács, Illés; Pacella, Elena; Radák, Zsolt

    2014-09-14

    Accumulating clinical evidence supports co-morbidity of irritable bowel, irritable eye and irritable mind symptoms. Furthermore, perturbation of the microbiota-host symbiosis (dysbiosis) is considered a common pathogenic mechanism connecting gastrointestinal, ocular and neuropsychiatric symptoms. Consequently, maintaining or restoring microbiota-host symbiosis represents a new approach to treat these symptoms or to prevent their relapses. Current treatment approach assigned a primary role to live probiotics alone or in combination with prebiotics to enhance colonization of beneficial bacteria and to strengthen the symbiosis. However, several papers showed major benefits of heat-killed probiotics as compared to their live counterparts on both intestinal and systemic symptoms. Recently, in addition to killing probiotics, in a proof of concept study lysates (fragments) of probiotics in combination with vitamins A, B, D and omega 3 fatty acids were successfully tested. These findings suggested a conceptual change in the approach addressed to both the microbiota and host as targets for intervention.

  2. Cognitive-behavioral therapy for patients with irritable bowel syndrome: current insights

    Directory of Open Access Journals (Sweden)

    Kinsinger SW

    2017-07-01

    Full Text Available Sarah W Kinsinger Behavioral Medicine for Digestive Health, Division of Gastroenterology and Nutrition, Loyola University Medical Center, Maywood, IL, USA Abstract: Irritable bowel syndrome (IBS is a chronic gastrointestinal (GI condition associated with significant health care utilization and quality-of-life impairment. Latest research indicates that the brain–gut axis plays a key role in the disorder, and the presence of psychological factors and central processing deficits contribute to symptom severity and disability. Psychological therapies as a whole have demonstrated good efficacy in reducing the severity of IBS symptoms. Cognitive-behavioral therapy (CBT has been tested most rigorously in multiple randomized controlled trials and consistently demonstrates significant and durable effects on IBS symptoms and quality of life. Various protocols for treating IBS have been developed, and most recent advances in the field include exposure-based treatments to target symptom-specific anxiety as well as modified delivery methods, including internet-based treatment models. Despite the well-documented advantages of CBT for IBS, it has been poorly disseminated and few patients have access to this treatment. The primary barrier to dissemination is the limited number of therapists with adequate training in GI psychology to provide this evidence-based intervention. Future developments in the field need to focus on training opportunities to equip more therapists to competently provide CBT for this population. Further efforts to develop telemedicine platforms for delivering this intervention will also improve accessibility for patients. Keywords: irritable bowel syndrome, functional gastrointestinal disorders, cognitive-behavioral therapy

  3. Synthesis, spectroscopic, computational (DFT/B3LYP), AChE inhibition and antioxidant studies of imidazole derivative

    Science.gov (United States)

    Ahmad, Faheem; Alam, Mohammad Jane; Alam, Mahboob; Azaz, Shaista; Parveen, Mehtab; Park, Soonheum; Ahmad, Shabbir

    2018-01-01

    The present study reports the synthesis and evaluation of biological properties of 3a,8a-dihydroxy-8-oxo-1,3,3a,8a-tetrahydroindeno[1,2-d]imidazol-2(1H)-iminium chloride (3). The structure was confirmed by the FTIR, NMR, MS, CHN microanalysis and X-ray crystallographic analysis. Quantum chemical calculations have been performed at B3LYP-D3/6-311++G(d,p) level of theory to study the molecular geometry, IR, (1H and 13C) NMR, UV/Vis spectra and other molecular parameters of the asymmetric unit of crystal of imidazole compound (3). An empirical dispersion correction to hybrid functional (B3LYP-D3) has been incorporated in the present calculations due to presence of non-covalent interaction, Cl⋯H-O, in the present compound. The remarkable agreement has been observed between theoretical data and those measured experimentally. Moreover, the Hirshfeld analysis was carried out to ascertain the secondary interactions and associated 2D fingerprint plots. The synthesized imidazole derivative showed promising antioxidant property and inhibitory activity against acetylcholinesterase (AChE). Molecular docking was also performed in order to explain in silico antioxidant studies and to ascertain the probable binding mode of compound with the amino acid residues of protein.

  4. Alternative methods for skin irritation testing: the current status : ECVAM skin irritation task force report 1

    NARCIS (Netherlands)

    Botham, P.A.; Earl, L.K.; Fentem, J.H.; Roguet, R.; Sandt, J.J.M.

    1998-01-01

    The ECVAM Skin Irritation Task Force was established in November 1996, primarily to prepare a report on the current status of the development and validation of alternative tests for skin irritation and corrosion and, in particular, to identify any appropriate non-animal tests for predicting human

  5. 5-HT in the enteric nervous system: gut function and neuropharmacology.

    Science.gov (United States)

    McLean, Peter G; Borman, Richard A; Lee, Kevin

    2007-01-01

    In recent times, the perception of functional gastrointestinal disorders such as irritable bowel syndrome (IBS) has shifted fundamentally. Such disorders are now thought of as serious diseases characterized by perturbations in the neuronal regulation of gastrointestinal function. The concept of visceral hypersensitivity, the characterization of neuronal networks in the 'brain-gut axis' and the identification of several novel 5-HT-mediated mechanisms have contributed to this shift. Here, we review how some of the more promising of these new mechanisms (e.g. those involving 5-HT transporters and the 5-HT(2B), 5-HT(7) and putative 5-HT(1p) receptors) might lead to a range of second-generation therapies that could revolutionize the treatment of functional gastrointestinal disorders, particularly IBS.

  6. Irritable bowel syndrome: new insights into symptom mechanisms and advances in treatment [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Robin Spiller

    2016-04-01

    Full Text Available Despite being one of the most common conditions leading to gastroenterological referral, irritable bowel syndrome (IBS is poorly understood. However, recent years have seen major advances. These include new understanding of the role of both inflammation and altered microbiota as well as the impact of dietary intolerances as illuminated by magnetic resonance imaging (MRI, which has thrown new light on IBS. This article will review new data on how excessive bile acid secretion mediates diarrhea and evidence from post infectious IBS which has shown how gut inflammation can alter gut microbiota and function. Studies of patients with inflammatory bowel disease (IBD have also shown that even when inflammation is in remission, the altered enteric nerves and abnormal microbiota can generate IBS-like symptoms. The efficacy of the low FODMAP diet as a treatment for bloating, flatulence, and abdominal discomfort has been demonstrated by randomized controlled trials. MRI studies, which can quantify intestinal volumes, have provided new insights into how FODMAPs cause symptoms. This article will focus on these areas together with recent trials of new agents, which this author believes will alter clinical practice within the foreseeable future.

  7. Chemical chaperones exceed the chaperone effects of RIC-3 in promoting assembly of functional α7 AChRs.

    Directory of Open Access Journals (Sweden)

    Alexander Kuryatov

    Full Text Available Functional α7 nicotinic acetylcholine receptors (AChRs do not assemble efficiently in cells transfected with α7 subunits unless the cells are also transfected with the chaperone protein RIC-3. Despite the presence of RIC-3, large amounts of these subunits remain improperly assembled. Thus, additional chaperone proteins are probably required for efficient assembly of α7 AChRs. Cholinergic ligands can act as pharmacological chaperones to promote assembly of mature AChRs and upregulate the amount of functional AChRs. In addition, we have found that the chemical chaperones 4-phenylbutyric acid (PBA and valproic acid (VPA greatly increase the amount of functional α7 AChRs produced in a cell line expressing both α7 and RIC-3. Increased α7 AChR expression allows assay of drug action using a membrane potential-sensitive fluorescent indicator. Both PBA and VPA also increase α7 expression in the SH-SY5Y neuroblastoma cell line that endogenously expresses α7 AChRs. VPA increases expression of endogenous α7 AChRs in hippocampal neurons but PBA does not. RIC-3 is insufficient for optimal assembly of α7 AChRs, but provides assay conditions for detecting additional chaperones. Chemical chaperones are a useful pragmatic approach to express high levels of human α7 AChRs for drug selection and characterization and possibly to increase α7 expression in vivo.

  8. Developmental trajectories of irritability and bidirectional associations with maternal depression.

    Science.gov (United States)

    Wiggins, Jillian Lee; Mitchell, Colter; Stringaris, Argyris; Leibenluft, Ellen

    2014-11-01

    Irritability is a dimensional trait in typical development and a common presenting symptom in many psychiatric disorders, including depression. However, little is known about the developmental trajectory of irritability or how child irritability interacts with maternal depression. The present study identifies classes of irritability trajectories from toddlerhood to middle childhood; characterizes maternal depression and other family, social environment, and child variables within each irritability trajectory class; and, as a more exploratory analysis, examines bidirectional associations between maternal depression and child irritability. A total of 4,898 families from the Fragile Families and Child Wellbeing Study reported on irritability symptoms at ages 3, 5, and 9 years, assessed with items from the Child Behavior Checklist. Parental major depressive episode was assessed using the Composite International Diagnostic Interview-Short Form at child ages 1, 3, 5, and 9 years. A latent class growth analysis identified 5 irritability classes: low decreasing; moderate decreasing; high steady; initially very high, then decreasing; and high increasing. Children with more severe irritability trajectories are more likely to have mothers with recurrent depression, and, with the exception of the most severe (high increasing irritability) class, were more likely to have mothers who were exposed to violence. Moreover, paternal depression and alcohol abuse, as well as maternal drug and alcohol abuse, were also risk factors for membership in the more severe irritability classes. A latent auto-regressive cross-lag model showed that child irritability at ages 3 and 5 years is associated with increased mother depression at ages 5 and 9, respectively. Conversely, mother depression at child ages 1 and 3 years is associated with increased child irritability at 3 and 5. Irritability development across toddlerhood and middle childhood has 5 main trajectory types, which differ on maternal

  9. Gut Microbiota-brain Axis

    Institute of Scientific and Technical Information of China (English)

    Hong-Xing Wang; Yu-Ping Wang

    2016-01-01

    Objective:To systematically review the updated information about the gut microbiota-brain axis.Data Sources:All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of"gut microbiota","gut-brain axis",and "neuroscience".Study Selection:All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed,with no limitation of study design.Results:It is well-recognized that gut microbiota affects the brain's physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully understood.Gut microbiota-brain axis may include gut microbiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous system.Moreover,there may be five communication routes between gut microbiota and brain,including the gut-brain's neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain barrier.The microbiome is used to define the composition and functional characteristics of gut microbiota,and metagenomics is an appropriate technique to characterize gut microbiota.Conclusions:Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain,which may provide a new way to protect the brain in the near future.

  10. Occupational irritant contact dermatitis diagnosed by analysis of contact irritants and allergens in the work environment.

    Science.gov (United States)

    Friis, Ulrik F; Menné, Torkil; Schwensen, Jakob F; Flyvholm, Mari-Ann; Bonde, Jens P E; Johansen, Jeanne D

    2014-12-01

    Irritant contact dermatitis (ICD) is a common diagnosis in patients with occupational contact dermatitis (OCD). Studies are lacking on the usefulness of material safety data sheets (MSDSs) in making the diagnosis of ICD. To characterize irritant exposures leading to the diagnosis of occupational ICD (OICD), and to evaluate the occurrence of concomitant exposures to contact allergens. We included 316 patients with suspected occupational hand dermatitis, referred to the Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, Denmark during January 2010-August 2011, in a programme consisting of a clinical examination, exposure assessment, and extensive patch/prick testing. OCD was diagnosed in 228 patients. Of these patients, 118 were diagnosed with OICD. The main irritant exposures identified were wet work (n = 64), gloves (n = 45), mechanical traumas (n = 19), and oils (n = 15). Exposure to specific irritant chemicals was found in 9 patients, and was identified from MSDSs/ingredients labelling in 8 of these patients. Review of MSDSs and ingredients labelling showed that 41 patients were exposed to 41 moderate to potent contact allergens, and 18 patients were exposed to 25 weak workplace contact allergens. In the present study, the systematic exposure assessment did not reveal any new irritants. MSDSs have a limited role in the investigation of ICD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Need for a comprehensive medical approach to the neuroimmuno-gastroenterology of irritable bowel syndrome

    Institute of Scientific and Technical Information of China (English)

    Pejman Katiraei; Gilberto Bultron

    2011-01-01

    Irritable bowel syndrome (IBS) is defined by the Rome Ⅲ criteria as symptoms of recurrent abdominal pain or discomfort with the onset of a marked change in bowel habits with no evidence of an inflammatory, anatomic,metabolic, or neoplastic process. As such, many clinicians regard IBS as a central nervous system problem of altered pain perception. Here, we review the recent literature and discuss the evidence that supports an organic based model, which views IBS as a complex,heterogeneous, inter-dependent, and multi-variable inflammatory process along the neuronal-gut axis. We delineate the organic pathophysiology of IBS, demonstrate the role of inflammation in IBS, review the possible differences between adult and pediatric IBS, discuss the merits of a comprehensive treatment model as taught by the Institute of Functional Medicine, and describe the potential for future research for this syndrome.

  12. Citral a fragrance allergen and irritant

    DEFF Research Database (Denmark)

    Heydorn, S; Menné, T; Andersen, Klaus Ejner

    2003-01-01

    Citral is a well known contact allergen and a contact irritant. Routine patch testing in the past may have been restricted because of possible irritant (IR) patch test responses. 586 consecutive patients, with hand eczema, were patch tested with a selection of fragrances including citral 2% petro...

  13. Manipulating the gut microbiota to maintain health and treat disease

    Directory of Open Access Journals (Sweden)

    Karen P. Scott

    2015-02-01

    Full Text Available Background: The intestinal microbiota composition varies between healthy and diseased individuals for numerous diseases. Although any cause or effect relationship between the alterations in the gut microbiota and disease is not always clear, targeting the intestinal microbiota might offer new possibilities for prevention and/or treatment of disease. Objective: Here we review some examples of manipulating the intestinal microbiota by prebiotics, probiotics, and fecal microbial transplants. Results: Prebiotics are best known for their ability to increase the number of bifidobacteria. However, specific prebiotics could potentially also stimulate other species they can also stimulate other species associated with health, like Akkermansia muciniphila, Ruminococcus bromii, the Roseburia/Enterococcus rectale group, and Faecalibacterium prausnitzii. Probiotics have beneficial health effects for different diseases and digestive symptoms. These effects can be due to the direct effect of the probiotic bacterium or its products itself, as well as effects of the probiotic on the resident microbiota. Probiotics can influence the microbiota composition as well as the activity of the resident microbiota. Fecal microbial transplants are a drastic intervention in the gut microbiota, aiming for total replacement of one microbiota by another. With numerous successful studies related to antibiotic-associated diarrhea and Clostridium difficile infection, the potential of fecal microbial transplants to treat other diseases like inflammatory bowel disease, irritable bowel syndrome, and metabolic and cardiovascular disorders is under investigation. Conclusions: Improved knowledge on the specific role of gut microbiota in prevention and treatment of disease will help more targeted manipulation of the intestinal microbiota. Further studies are necessary to see the (long term effects for health of these interventions.

  14. Lack of Ach1 CoA-Transferase Triggers Apoptosis and Decreases Chronological Lifespan in Yeast

    International Nuclear Information System (INIS)

    Orlandi, Ivan; Casatta, Nadia; Vai, Marina

    2012-01-01

    ACH1 encodes a mitochondrial enzyme of Saccharomyces cerevisiae endowed with CoA-transferase activity. It catalyzes the CoASH transfer from succinyl-CoA to acetate generating acetyl-CoA. It is known that ACH1 inactivation results in growth defects on media containing acetate as a sole carbon and energy source which are particularly severe at low pH. Here, we show that chronological aging ach1Δ cells which accumulate a high amount of extracellular acetic acid display a reduced chronological lifespan. The faster drop of cell survival is completely abrogated by alleviating the acid stress either by a calorie restricted regimen that prevents acetic acid production or by transferring chronologically aging mutant cells to water. Moreover, the short-lived phenotype of ach1Δ cells is accompanied by reactive oxygen species accumulation, severe mitochondrial damage, and an early insurgence of apoptosis. A similar pattern of endogenous severe oxidative stress is observed when ach1Δ cells are cultured using acetic acid as a carbon source under acidic conditions. On the whole, our data provide further evidence of the role of acetic acid as cell-extrinsic mediator of cell death during chronological aging and highlight a primary role of Ach1 enzymatic activity in acetic acid detoxification which is important for mitochondrial functionality.

  15. Expression and role of 5-HT7 receptor in brain and intestine in rats with irritable bowel syndrome.

    Science.gov (United States)

    Zou, Bai-cang; Dong, Lei; Wang, Yan; Wang, Sheng-hao; Cao, Ming-bo

    2007-12-05

    The 5-hydroxytryptamine7 receptor (5-HT(7) receptor, 5-HT(7)R) plays an important role in the regulation of smooth muscle relaxation and visceral sensation and might be involved in the pathogenesis of the gastrointestinal dyskinesia, abdominal pain and visceral paresthesia in irritable bowel syndrome (IBS). The aim of this study was to investigate the role of the 5-HT(7) receptor in the pathogenesis of IBS. A rat model of irritable bowel syndrome with diarrhea (IBS-D) was established by colonic instillation of acetic acid and restraint stress. A rat model with irritable bowel syndrome with constipation (IBS-C) was established by stomach irrigated with 0 - 4 degrees C cool water daily for 14 days. The content and distribution of 5-HT in the brain and gut were examined by immunohistochemistry and the mRNA expression of the 5-HT(7) receptor was determined by fluorescent quantitative reverse transcription polymerase chain reaction. The accumulation of cyclic adenosine monophosphate (cAMP) in all the same tissues was measured by radioimmunity. The models of IBS were reliable by identification. The immunohistochemistry results showed that there were significantly more 5-HT positive cells in the IBS-D group than in the control group in the hippocampus, hypothalamus, jejunum, ileum, proximate colon and distal colon (P intestine is related to the IBS pathogenesis. The up-regulated expression of the 5-HT(7) receptor in the brain and colon might play an important role in the pathogenesis of IBS-C.

  16. IRRITATED BOWEL SYNDROME IN CHILDREN

    Directory of Open Access Journals (Sweden)

    V. F. Privorotskiy

    2012-01-01

    Full Text Available Irritated bowel syndrome is a significant and underestimated problem in childhood. This condition is not so good studied in pediatrics in comparison with adult practice. Pediatricians often diagnosed this disease in infants and young children without proper reasons. The authors analyze current opinions about etiology and pathogenesis, clinical presentation, diagnosticsand treatment of irritated bowel syndrome in children. An emphasis is made on diagnostic criteria, which allow suggesting and confirming the diagnosis.

  17. GUTs and supersymmetric GUTs in the very early universe

    International Nuclear Information System (INIS)

    Ellis, J.

    1983-01-01

    This talk is intended as background material for many of the other talks treating the possible applications of GUTs to the very early universe. It starts with a review of the present theoretical and phenomenological status of GUTs and then goes on to raise some new issues for their prospective cosmological applications which arise in supersymmetric (susy) GUTs. (author)

  18. Is irritable bowel syndrome an infectious disease?

    Science.gov (United States)

    Thompson, John Richard

    2016-01-28

    Irritable bowel syndrome (IBS) is the most common of all gastroenterological diseases. While many mechanisms have been postulated to explain its etiology, no single mechanism entirely explains the heterogeneity of symptoms seen with the various phenotypes of the disease. Recent data from both basic and clinical sciences suggest that underlying infectious disease may provide a unifying hypothesis that better explains the overall symptomatology. The presence of small intestinal bowel overgrowth (SIBO) has been documented in patients with IBS and reductions in SIBO as determined by breath testing correlate with IBS symptom improvement in clinical trials. The incidence of new onset IBS symptoms following acute infectious gastroenteritis also suggests an infectious cause. Alterations in microbiota-host interactions may compromise epithelial barrier integrity, immune function, and the development and function of both central and enteric nervous systems explaining alterations in the brain-gut axis. Clinical evidence from treatment trials with both probiotics and antibiotics also support this etiology. Probiotics appear to restore the imbalance in the microflora and improve IBS-specific quality of life. Antibiotic trials with both neomycin and rifaximin show improvement in global IBS symptoms that correlates with breath test normalization in diarrhea-predominant patients. The treatment response to two weeks of rifaximin is sustained for up to ten weeks and comparable results are seen in symptom reduction with retreatment in patients who develop recurrent symptoms.

  19. Acetylcholinesterase Inhibitors (AChEI's for the treatment of visual hallucinations in schizophrenia: A review of the literature

    Directory of Open Access Journals (Sweden)

    Patel Sachin S

    2010-09-01

    Full Text Available Abstract Background Visual hallucinations occur in various neurological diseases, but are most prominent in Lewy body dementia, Parkinson's disease and schizophrenia. The lifetime prevalence of visual hallucinations in patients with schizophrenia is much more common than conventionally thought and ranges from 24% to 72%. Cortical acetylcholine (ACh depletion has been associated with visual hallucinations; the level of depletion being related directly to the severity of the symptoms. Current understanding of neurobiological visual processing and research in diseases with reduced cholinergic function, suggests that AChEI's may prove beneficial in treating visual hallucinations. This offers the potential for targeted drug therapy of clinically symptomatic visual hallucinations in patients with schizophrenia using acetylcholinesterase inhibition. Methods A systematic review was carried out investigating the evidence for the effects of AChEI's in treating visual hallucinations in Schizophrenia. Results No evidence was found relating to the specific role of AChEI's in treating visual hallucinations in this patient group. Discussion Given the use of AChEI's in targeted, symptom specific treatment in other neuropsychiatric disorders, it is surprising to find no related literature in schizophrenia patients. The use of AChEI's in schizophrenia has investigated effects on cognition primarily with non cognitive effects measured more broadly. Conclusions We would suggest that more focused research into the effects of AChEI's on positive symptoms of schizophrenia, specifically visual hallucinations, is needed.

  20. Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome.

    Science.gov (United States)

    Sagami, Y; Shimada, Y; Tayama, J; Nomura, T; Satake, M; Endo, Y; Shoji, T; Karahashi, K; Hongo, M; Fukudo, S

    2004-07-01

    Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of alpha-helical CRH (alphahCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patients. Ten normal healthy subjects and 10 IBS patients, diagnosed according to the Rome II criteria, were studied. The tone of the descending colon and intraluminal pressure of the sigmoid colon were measured at baseline, during rectal electrical stimulation (ES), and at recovery after administration of saline. Visceral perception after colonic distension or rectal ES was evaluated as threshold values on an ordinate scale. The same measurements were repeated after administration of alphahCRH (10 micro g/kg). ES induced significantly higher motility indices of the colon in IBS patients compared with controls. This response was significantly suppressed in IBS patients but not in controls after administration of alphahCRH. Administration of alphahCRH induced a significant increase in the barostat bag volume of controls but not in that of IBS patients. alphahCRH significantly reduced the ordinate scale of abdominal pain and anxiety evoked by ES in IBS patients. Plasma adrenocorticotropic hormone and serum cortisol levels were generally not suppressed by alphahCRH. Peripheral administration of alphahCRH improves gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation, without affecting the hypothalamo-pituitary-adrenal axis in IBS patients.

  1. Chemical and molecular factors in irritable bowel syndrome: current knowledge, challenges, and unanswered questions.

    Science.gov (United States)

    Camilleri, Michael; Oduyebo, Ibironke; Halawi, Houssam

    2016-11-01

    Several chemical and molecular factors in the intestine are reported to be altered and to have a potentially significant role in irritable bowel syndrome (IBS), particularly in IBS with diarrhea. These include bile acids; short-chain fatty acids; mucosal barrier proteins; mast cell products such as histamine, proteases, and tryptase; enteroendocrine cell products; and mucosal mRNAs, proteins, and microRNAs. This article reviews the current knowledge and unanswered questions in the pathobiology of the chemical and molecular factors in IBS. Evidence continues to point to significant roles in pathogenesis of these chemical and molecular mechanisms, which may therefore constitute potential targets for future research and therapy. However, it is still necessary to address the interaction between these factors in the gut and to appraise how they may influence hypervigilance in the central nervous system in patients with IBS. Copyright © 2016 the American Physiological Society.

  2. Preparation and comparison of a-C:H coatings using reactive sputter techniques

    Energy Technology Data Exchange (ETDEWEB)

    Keunecke, M., E-mail: martin.keunecke@ist.fraunhofer.d [Fraunhofer Institute for Surface Engineering and Thin Films (IST), Braunschweig (Germany); Weigel, K.; Bewilogua, K. [Fraunhofer Institute for Surface Engineering and Thin Films (IST), Braunschweig (Germany); Cremer, R.; Fuss, H.-G. [CemeCon AG, Wuerselen (Germany)

    2009-12-31

    Amorphous hydrogenated carbon (a-C:H) coatings are widely used in several industrial applications. These coatings commonly will be prepared by plasma activated chemical vapor deposition (PACVD). The main method used to prepare a-C:H coating in industrial scale is based on a glow discharge in a hydrocarbon gas like acetylene or methane using a substrate electrode powered with medium frequency (m.f. - some 10 to 300 kHz). Some aims of further development are adhesion improvement, increase of hardness and high coating quality on complex geometries. A relatively new and promising technique to fulfil these requirements is the deposition of a-C:H coatings by a reactive d.c. magnetron sputter deposition from a graphite target with acetylene as reactive gas. An advancement of this technique is the deposition in a pulsed magnetron sputter process. Using these three mentioned techniques a-C:H coatings were prepared in the same deposition machine. For adhesion improvement different interlayer systems were applied. The effect of different substrate bias voltages (d.c. and d.c. pulse) was investigated. By applying the magnetron sputter technique in the d.c. pulse mode, plastic hardness values up to 40 GPa could be reached. Besides hardness other mechanical properties like resistance against abrasive wear were measured and compared. Cross sectional SEM images showed the growth structure of the coatings.

  3. Occupational irritant contact dermatitis diagnosed by analysis of contact irritants and allergens in the work environment

    DEFF Research Database (Denmark)

    Friis, Ulrik F; Menné, Torkil; Schwensen, Jakob F

    2014-01-01

    BACKGROUND: Irritant contact dermatitis (ICD) is a common diagnosis in patients with occupational contact dermatitis (OCD). Studies are lacking on the usefulness of material safety data sheets (MSDSs) in making the diagnosis of ICD. OBJECTIVE: To characterize irritant exposures leading...... to the diagnosis of occupational ICD (OICD), and to evaluate the occurrence of concomitant exposures to contact allergens. METHODS: We included 316 patients with suspected occupational hand dermatitis, referred to the Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, Denmark during......), mechanical traumas (n = 19), and oils (n = 15). Exposure to specific irritant chemicals was found in 9 patients, and was identified from MSDSs/ingredients labelling in 8 of these patients. Review of MSDSs and ingredients labelling showed that 41 patients were exposed to 41 moderate to potent contact...

  4. GUTs and supersymmetric GUTs in the very early universe

    International Nuclear Information System (INIS)

    Ellis, J.

    1982-10-01

    This talk is intended as background material for many of the other talks treating the possible applications of GUTs to the very early universe. I start with a review of the present theoretical and phenomenological status of GUTs before going on to raise some new issues for their prospective cosmological applications which arise in supersymmetric (susy) GUTs. The first section is an update on conventional GUTs, which is followed by a reminder of some of the motivations for going supersymmetric. There then follows a simple primer on susy and a discussion of the structure and phenomenology of simple sysy GUTs. Finally we come to the cosmological issues, including problems arising from the degeneracy of susy minima, baryosynthesis and supersymmetric inflation, the possibility that gravity is an essential complication in constructing susy GUTs and discussing their cosmology, and the related question of what mass range is allowed for the gravitino. Several parts of this write-up contain new material which has emerged either during the Workshop or subsequently. They are included here for completeness and the convenience of the prospective reader. Wherever possible, these anachronisms will be flagged so as to keep straight the historical record

  5. A cross-cultural perspective on irritable bowel syndrome.

    Science.gov (United States)

    Gerson, Charles D; Gerson, Mary-Joan

    2010-01-01

    Irritable bowel syndrome is a functional gastrointestinal illness, defined by symptoms. Irritable bowel syndrome has been described as a biopsychosocial condition, in which colonic dysfunction is affected by psychological and social factors. As a result of this unusual constellation, irritable bowel syndrome may be subject to cultural variables that differ in different parts of the globe. In this article, we describe some of the ways in which irritable bowel syndrome may be experienced differently, depending on local belief systems, psychological pressures, acceptance or resistance to a mind-body paradigm, and breakdown in support or relationship structure. Examples are given in which irritable bowel syndrome investigators from countries around the world describe various aspects of the syndrome that may affect the illness experience of their patients. We describe our own research studies that have demonstrated possible adverse effects on disease severity from relationship conflict, attribution of symptoms to physical rather than emotional cause, and the belief that irritable bowel syndrome is enduring and mysterious. Also described is our finding that symptom patterns may differ significantly between different geographic locations. Finally, we discuss the importance of "cultural competence" on the part of healthcare professionals in regard to caring for patients of diverse cultural backgrounds. © 2010 Mount Sinai School of Medicine.

  6. Occupational irritant contact dermatitis due to petroleum naphtha

    OpenAIRE

    Aslı Aytekin; Arzu Karataş Toğral

    2014-01-01

    Irritant contact dermatitis (ICD) is responsible for the vast majority of occupational contact dermatitis and usually seen in professional groups working with wet hand. However, today, with the increasing business lines, employees are exposed to a variety of irritants. Occupational exposure to many chemicals and toxic irritants affect not only the skin, but also the other systems. Therefore, this situation resulting with loss of work and changes in business may become a public health problem....

  7. GUTs without guts

    Energy Technology Data Exchange (ETDEWEB)

    Gato-Rivera, B. [NIKHEF Theory Group, Science Park 105, 1098 XG Amsterdam (Netherlands); Instituto de Física Fundamental, IFF-CSIC, Serrano 123, Madrid 28006 (Spain); Schellekens, A.N., E-mail: t58@nikhef.nl [NIKHEF Theory Group, Science Park 105, 1098 XG Amsterdam (Netherlands); Instituto de Física Fundamental, IFF-CSIC, Serrano 123, Madrid 28006 (Spain); IMAPP, Radboud Universiteit, Nijmegen (Netherlands)

    2014-06-15

    The structure of a Standard Model family is derived in a class of brane models with a U(M)×U(N) factor, from two mildly anthropic requirements: a massless photon and a universe that does not turn into a plasma of massless charged particles. If we choose M=3 and N=2, the only option is shown to be the Standard Model with an undetermined number of families. We do not assume the U(1) embedding, charge quantization, family repetition, nor the fermion representations; all of these features are derived, assuming a doublet Higgs. With a slightly stronger assumption even the Higgs representation is determined. We also consider a more general class, requiring an asymptotically free strong SU(M) (with M⩾3) interaction from the first factor and an electromagnetic U(1) embedded in both factors. We allow Higgs symmetry breaking of the U(N)×U(1) flavor group by at most one Higgs boson in any representation, combined with any allowed chiral symmetry breaking by SU(M). For M=3 there is a large number of solutions with an unbroken U(1). In all of these, “quarks” have third-integral charges and color singlets have integer charges in comparison to leptons. Hence Standard Model charge quantization holds for any N. Only for N=2 these models allow an SU(5) GUT extension, but this extension offers no advantages whatsoever for understanding the Standard Model; it only causes complications, such as the doublet–triplet splitting problem. Although all these models have a massless photon, all except the Standard Model are ruled out by the second anthropic requirement. In this class of brane models the Standard Model is realized as a GUT with its intestines removed, to keep only the good parts: a GUT without guts.

  8. GUTs without guts

    International Nuclear Information System (INIS)

    Gato-Rivera, B.; Schellekens, A.N.

    2014-01-01

    The structure of a Standard Model family is derived in a class of brane models with a U(M)×U(N) factor, from two mildly anthropic requirements: a massless photon and a universe that does not turn into a plasma of massless charged particles. If we choose M=3 and N=2, the only option is shown to be the Standard Model with an undetermined number of families. We do not assume the U(1) embedding, charge quantization, family repetition, nor the fermion representations; all of these features are derived, assuming a doublet Higgs. With a slightly stronger assumption even the Higgs representation is determined. We also consider a more general class, requiring an asymptotically free strong SU(M) (with M⩾3) interaction from the first factor and an electromagnetic U(1) embedded in both factors. We allow Higgs symmetry breaking of the U(N)×U(1) flavor group by at most one Higgs boson in any representation, combined with any allowed chiral symmetry breaking by SU(M). For M=3 there is a large number of solutions with an unbroken U(1). In all of these, “quarks” have third-integral charges and color singlets have integer charges in comparison to leptons. Hence Standard Model charge quantization holds for any N. Only for N=2 these models allow an SU(5) GUT extension, but this extension offers no advantages whatsoever for understanding the Standard Model; it only causes complications, such as the doublet–triplet splitting problem. Although all these models have a massless photon, all except the Standard Model are ruled out by the second anthropic requirement. In this class of brane models the Standard Model is realized as a GUT with its intestines removed, to keep only the good parts: a GUT without guts

  9. Tissue Friendly Pendulum: Soft Liner to prevent Tissue Irritation

    Directory of Open Access Journals (Sweden)

    Siddharth Shashidhar Revankar

    2014-01-01

    Full Text Available Palatal mucosal irritation is commonly encountered with the Pendulum appliance. The efficiency of soft liners in reducing tissue irritation has been well documented in the field of prosthodontics. The following article describes an innovative technique where soft liner can be used to reduce palatal mucosal irritation caused by pendulum appliance.

  10. Review of Irritable Bowel Syndrome Treatment

    Directory of Open Access Journals (Sweden)

    Ghadir M.R.

    2010-06-01

    Full Text Available Background and Objectives: Irritable bowel syndrome is one of the most common functional gastrointestinal disorders striking 10-20% of the world population. Although most patients do not take medical assistance, this disease enforces significant cost on the patient and health systems and has negative effects on quality of life of the individual. After diagnosis ,treatment of this disease is the next step. Many pathways of treatment has been introduced and the efficacy of each other has been established in one way or another. The first step in the path of treatment is education and confidence of patients that might also be the most important step. Fiber diet, probiotic, anti-cholinergic and anti antispasmodics, laxatives, anti-diarrhea, the drugs affecting serotonin receptors, antidepressants and anti-anxiety, the chloride channel activator and non-drug methods such as cognitive-behavior therapy, hypnotherapy, acupuncture and herbal medicine each of which has been tested on irritable bowel syndrome and efficacy of each one has been indicated in one way or another. This paper tried to outline new treatments available in addition to categorization and discussion of various treatments for irritable bowel syndrome.Keywords: Irritable Bowel Syndrome; Probiotics; Parasmpatholytics; Laxatives.

  11. Aspects of the non-pharmacological treatment of irritable bowel syndrome.

    Science.gov (United States)

    Eriksson, Elsa Maria; Andrén, Kristina Ingrid; Kurlberg, Göran Karl; Eriksson, Henry Ture

    2015-10-28

    Irritable bowel syndrome (IBS) is one of the most commonly diagnosed gastrointestinal conditions. It represents a significant healthcare burden and remains a clinical challenge. Over the years IBS has been described from a variety of different perspectives; from a strict illness of the gastrointestinal tract (medical model) to a more complex multi-symptomatic disorder of the brain-gut axis (biopsychosocial/psychosomatic model). In this article we present aspects of the pathophysiology and the non-pharmacological treatment of IBS based on current knowledge. Effects of conditioned stress and/or traumatic influences on the emotional system (top-down) as well as effects on the intestine through stressors, infection, inflammation, food and dysbiosis (bottom-up) can affect brain-gut communication and result in dysregulation of the autonomic nervous system (ANS), playing an important role in the pathophysiology of IBS. Conditioned stress together with dysregulation of the autonomic nervous system and the emotional system may involve reactions in which the distress inside the body is not recognized due to low body awareness. This may explain why patients have difficulty identifying their symptoms despite dysfunction in muscle tension, movement patterns, and posture and biochemical functions in addition to gastrointestinal symptoms. IBS shares many features with other idiopathic conditions, such as fibromyalgia, chronic fatigue syndrome and somatoform disorders. The key to effective treatment is a thorough examination, including a gastroenterological examination to exclude other diseases along with an assessment of body awareness by a body-mind therapist. The literature suggests that early interdisciplinary diagnostic co-operation between gastroenterologists and body-mind therapists is necessary. Re-establishing balance in the ANS is an important component of IBS treatment. This article discusses the current knowledge of body-mind treatment, addressing the topic from a

  12. Mind-altering with the gut: Modulation of the gut-brain axis with probiotics.

    Science.gov (United States)

    Kim, Namhee; Yun, Misun; Oh, Young Joon; Choi, Hak-Jong

    2018-03-01

    It is increasingly evident that bidirectional interactions exist among the gastrointestinal tract, the enteric nervous system, and the central nervous system. Recent preclinical and clinical trials have shown that gut microbiota plays an important role in these gut-brain interactions. Furthermore, alterations in gut microbiota composition may be associated with pathogenesis of various neurological disorders, including stress, autism, depression, Parkinson's disease, and Alzheimer's disease. Therefore, the concepts of the microbiota-gut-brain axis is emerging. Here, we review the role of gut microbiota in bidirectional interactions between the gut and the brain, including neural, immune-mediated, and metabolic mechanisms. We highlight recent advances in the understanding of probiotic modulation of neurological and neuropsychiatric disorders via the gut-brain axis.

  13. Carcinogenesis after sublethal ionizing irradiation and regular avoidance irritation

    International Nuclear Information System (INIS)

    Kalisnik, M.; Vraspir-Porenta, O.; Logonder-Mlinsek, M.; Zorc-Pleskovic, R.; Pajer, Z.; Kham-Lindtner, T.; Zorc, M.; Skrk, J.

    1982-01-01

    160 mice of the BALB/C strain of both sexes, aged 3 months, were divided into four equal groups of which two were regularly irritated by a combination of an optical signal and electrical stroke. After one month of irritation one nonirritated and one irritated group were whole body irradiated with an acute dose of 6.65 Gy (1.83 Gy/min), the other two groups were sham irradiated. The mice lived until spontaneous death or one year after irradiation, when the rest of the animals were sacrificed. Malignant tumors were recorded. Irradiation shortened the survival time while the irritation had an appeasing, compensatory effect, more marked in the males than in the females. After irradiation the number and assortment of the tumors increased and the latent period was significantly shorter. In the irritated animals the number and assortment of the malignant tumors were reduced and the latent time period tended to be longer. These differences, however, were not statistically significant. In spite of some differences the response of both sexes to irradiation and irritation or their combination was similar. (author)

  14. The human gut resistome.

    Science.gov (United States)

    van Schaik, Willem

    2015-06-05

    In recent decades, the emergence and spread of antibiotic resistance among bacterial pathogens has become a major threat to public health. Bacteria can acquire antibiotic resistance genes by the mobilization and transfer of resistance genes from a donor strain. The human gut contains a densely populated microbial ecosystem, termed the gut microbiota, which offers ample opportunities for the horizontal transfer of genetic material, including antibiotic resistance genes. Recent technological advances allow microbiota-wide studies into the diversity and dynamics of the antibiotic resistance genes that are harboured by the gut microbiota ('the gut resistome'). Genes conferring resistance to antibiotics are ubiquitously present among the gut microbiota of humans and most resistance genes are harboured by strictly anaerobic gut commensals. The horizontal transfer of genetic material, including antibiotic resistance genes, through conjugation and transduction is a frequent event in the gut microbiota, but mostly involves non-pathogenic gut commensals as these dominate the microbiota of healthy individuals. Resistance gene transfer from commensals to gut-dwelling opportunistic pathogens appears to be a relatively rare event but may contribute to the emergence of multi-drug resistant strains, as is illustrated by the vancomycin resistance determinants that are shared by anaerobic gut commensals and the nosocomial pathogen Enterococcus faecium.

  15. Neonikotinoid İnsektisitlere Bağlı Olarak Drosophila melanogaster’in AChE Aktivitesinde Meydana Gelen Değişikliklerin Bitkisel Ekstraktlar ile Giderilmesi Üzerine Araştırmalar

    Directory of Open Access Journals (Sweden)

    Sedat Ünver

    2014-12-01

    Full Text Available Bu çalışmada, Drosophila melanogaster’in ergin bireylerinde bulunan asetil kolinesteraz (AChE enzim aktivitesi üzerine İmidakloprid (İMİ ve Asetamiprid (ASE  insektisitlerinin etkileri araştırılmıştır. Ayrıca farklı bitkilere ait su ekstraktlarının (Salvia lavandulifolia, Hypericum scabrum, Capsella bursa-pastoris ve Teucrium orientale iyileştirici etkileri de in vivo olarak incelenmiştir. Bu amaçla iki deney grubu oluşturulmuştur. İlk deney grubunda ergin bireylere yalnızca farklı dozlarda insektisit (0,5; 1,0; 1,5 ve 2,0 ppm, diğer deney grubunda ise insektisit + bitki ekstraktları (1:1 v/v birlikte uygulanmıştır. Uygulamalar sonucunda insektisitler doz artışına bağlı olarak ergin bireylerde AChE aktivitesini artırmıştır (P<0,05. Ancak insektisitler bitkisel ekstraktlar ile birlikte uygulanınca enzim aktivitesi tekrar kontrol grubuna yaklaşmıştır (P<0,05.

  16. Emulsifiers' composition modulates venous irritation of the nanoemulsions as a lipophilic and venous irritant drug delivery system.

    Science.gov (United States)

    Mao, Chengwen; Wan, Jiangling; Chen, Huabing; Xu, Huibi; Yang, Xiangliang

    2009-01-01

    In this study, a nanoemulsion (NE) system was investigated for intravenous delivery of lipophilic and venous irritant drugs. NEs were prepared to deliver diallyl trisulfide (DT) for systemic therapy of bacterial and fungal infection, egg phospholipid was chosen as the main emulsifier, and two co-emulsifiers were also incorporated, including Poloxamer 188 (P188) and Solutol HS 15 (S15). Soybean oil was used as the dispersed phases, forming stable DT NEs with small particle sizes. The venous irritation of DT NEs was evaluated by in vitro human umbilical cord endothelial cells (CRL 1730) compatibility model with the intracellular adenosine triphosphate (ATP) and guanosine triphosphate (GTP) concentrations as the indices. The intracellular ATP and GTP reduction changed with the incorporation of a variety of co-emulsifiers, which varied in a free DT concentration-dependent manner. It was deduced that the free DT concentrations of NEs containing co-emulsifiers were determined by the partition coefficient of DT between oil and surfactant buffer solution. In conclusion, NE was an appropriate delivery system for lipophilic and venous irritant drug, and optimization of the composition of emulsifiers was an effective method to alleviate the venous irritation of DT NEs.

  17. The impact of intolerance of uncertainty, worry and irritability on quality of life in persons with epilepsy: irritability as mediator.

    Science.gov (United States)

    Barahmand, Usha; Haji, Afsar

    2014-10-01

    Epilepsy is a neurological disorder afflicting many people in the world. The impact of epilepsy on the quality of life of those afflicted with epilepsy is greater than the limitations imposed by the seizures alone. Among the several psychological disorders found to be comorbid with epilepsy are anxiety and depression, both of which impair quality of life in epilepsy. Some studies have reported that the anxiety seen in epilepsy is characterized by worry while the depression seen is characterized by irritability. A concept common to both anxiety and depression is intolerance of uncertainty. Therefore, the study explores the relationship between intolerance of uncertainty, worry and irritability and their association to quality of life in epilepsy. A descriptive-correlational research method was used and the research sample comprised 60 consecutive referrals seeking outpatient neurological services for epilepsy at Alavi Hospital in Ardebil. Data were collected by administering the Penn State Worry Questionnaire, Intolerance of Uncertainty Scale, Irritability Questionnaire and Quality of Life in Epilepsy Inventory. Data were analyzed using Pearson's correlation coefficients and multivariate regression analysis. Mediation and moderation analyses were conducted. Findings indicated that intolerance of uncertainty, worry and irritability have unique significant effects on quality of life. The implications are that interventions aimed at improving the quality of life of patients with epilepsy should address their feelings of uncertainty, worry and irritability. Furthermore, irritability seems to mediate the impact of both intolerance of uncertainty and worry on quality of life of individuals with epilepsy. No significant moderation effects were noted. Results underscore the important role of irritability in the quality of life of persons with epilepsy. The findings are discussed with reference to the possibility of particular predisposing temperaments and add credence to

  18. Gut microbiota’s effect on mental health: The gut-brain axis

    Directory of Open Access Journals (Sweden)

    Megan Clapp

    2017-09-01

    Full Text Available The bidirectional communication between the central nervous system and gut microbiota, referred to as the gut-brain-axis, has been of significant interest in recent years. Increasing evidence has associated gut microbiota to both gastrointestinal and extragastrointestinal diseases. Dysbiosis and inflammation of the gut have been linked to causing several mental illnesses including anxiety and depression, which are prevalent in society today. Probiotics have the ability to restore normal microbial balance, and therefore have a potential role in the treatment and prevention of anxiety and depression. This review aims to discuss the development of the gut microbiota, the linkage of dysbiosis to anxiety and depression, and possible applications of probiotics to reduce symptoms.

  19. The Military Deployment Human Exposure Assessment Study (MDHEXAS): Blood and Urine Exposure Biomarkers as Environmental Surveillance Tools for Assessing Military Personnel Exposure to Chemicals During Deployment to Camp McGovern, Bosnia

    Science.gov (United States)

    2003-01-01

    dysp = Dyspnea euph = euphoria excitement = excited fib = fibrosis flush face = flush face ftg = fatigue Head = Headache Gidd = giddiness inco...nausea Neck = neck ache nose = irritated nose Pallor Pulm edema= pulmonar y edema Resp sys = Respiratory System skin = irritated skin som = somnolence

  20. Gut-Sourced Vasoactive Intestinal Polypeptide Induced by the Activation of α7 Nicotinic Acetylcholine Receptor Substantially Contributes to the Anti-inflammatory Effect of Sinomenine in Collagen-Induced Arthritis

    Directory of Open Access Journals (Sweden)

    MengFan Yue

    2018-06-01

    Full Text Available Sinomenine has long been used for the treatment of rheumatoid arthritis in China. However, its anti-inflammatory mechanism is still debatable because the in vitro minimal effective concentration (≥250 μM is hardly reached in either synovium or serum after oral administration at a therapeutic dose. Recent findings suggest that the α7 nicotinic acetylcholine receptor (α7nAChR might mediate the inhibitory effect of sinomenine on macrophage activation, which attracts us to explore the anti-arthritis mechanism of sinomenine by taking neuroendocrine-inflammation axis into consideration. Here, we showed that orally administered sinomenine ameliorated the systemic inflammation of collagen-induced arthritis (CIA rats, which was significantly diminished by either vagotomy or the antagonists of nicotinic acetylcholine receptors (especially the antagonist of α7nAChR, but not by the antagonists of muscarinic receptor. Sinomenine might bind to α7nAChR through interacting with the residues Tyr184 and Tyr191 in the pocket. In addition, the generation of vasoactive intestinal polypeptide (VIP from the gut of CIA rats and cultured neuron-like cells was selectively enhanced by sinomenine through the activation of α7nAChR-PI3K/Akt/mTOR pathway. The elevated levels of VIP in the serum and small intestine of rats were negatively correlated with the scores of joint destruction. The crucial role of VIP in the anti-arthritic effect of sinomenine was confirmed by using VIP hybrid, a non-specific antagonist of VIP receptor. Taken together, intestine-sourced VIP mediates the anti-arthritic effect of sinomenine, which is generated by the activation of α7nAChR.

  1. From topical antidote against skin irritants to a novel counter-irritating and anti-inflammatory peptide

    International Nuclear Information System (INIS)

    Brodsky, Berta; Erlanger-Rosengarten, Avigail; Proscura, Elena; Shapira, Elena; Wormser, Uri

    2008-01-01

    The primary purpose of the present study was to investigate the mechanism of the counter-irritating activity of topical iodine against skin lesions induced by chemical and thermal stimuli. The hypothesis that iodine exerts its activity by inducing an endogenous anti-inflammatory factor was confirmed by exposing guinea pig skin to heat stimulus followed by topical iodine treatment and skin extraction. Injection of the extract into naive guinea pigs reduced heat-induced irritation by 69%. The protective factor, identified as a new nonapeptide (histone H2A 36-44, H-Lys-Gly-Asn-Tyr-Ala-Glu-Arg-Ileu-Ala-OH), caused reduction of 40% in irritation score in heat-exposed guinea pigs. The murine analog (H-Lys-Gly-His-Tyr-Ala-Glu-Arg-Val-Gly-OH, termed IIIM1) reduced sulfur mustard (SM)-induced ear swelling at a dose-dependent bell-shape manner reaching peak activity of 1 mg/kg. Cultured keratinocytes transfected with the peptide were more resistant towards SM than the control cells. The peptide suppressed oxidative burst in activated neutrophils in a concentration-dependent manner. In addition, the peptide reduced glucose oxidase-induced skin edema in mice at a dose-dependent bell-shape manner. Apart from thermal and chemical-induced skin irritation this novel peptide might be of potential use in chronic dermal disorders such as psoriasis and pemphigus as well as non-dermal inflammatory diseases like multiple sclerosis, arthritis and colitis

  2. The irritancy of metalworking fluids: a laser Doppler flowmetry study

    NARCIS (Netherlands)

    de Boer, E. M.; Scholten, R. J.; van Ketel, W. G.; Bruynzeel, D. P.

    1990-01-01

    Irritant contact dermatitis is common in metalworkers exposed to metalworking fluids (MWF). The irritancy of 3 commercially available water-based cutting fluids in maximal user's concentration and 2 neat oils was investigated in 23 healthy volunteers. Additionally, the irritancy of some groups of

  3. Tail gut cyst.

    Science.gov (United States)

    Rao, G Mallikarjuna; Haricharan, P; Ramanujacharyulu, S; Reddy, K Lakshmi

    2002-01-01

    The tail gut is a blind extension of the hindgut into the tail fold just distal to the cloacal membrane. Remnants of this structure may form tail gut cyst. We report a 14-year-old girl with tail gut cyst that presented as acute abdomen. The patient recovered after cyst excision.

  4. The current agonists and positive allosteric modulators of α7 nAChR for CNS indications in clinical trials

    Directory of Open Access Journals (Sweden)

    Taoyi Yang

    2017-11-01

    Full Text Available The alpha-7 nicotinic acetylcholine receptor (α7 nAChR, consisting of homomeric α7 subunits, is a ligand-gated Ca2+-permeable ion channel implicated in cognition and neuropsychiatric disorders. Enhancement of α7 nAChR function is considered to be a potential therapeutic strategy aiming at ameliorating cognitive deficits of neuropsychiatric disorders such as Alzheimer's disease (AD and schizophrenia. Currently, a number of α7 nAChR modulators have been reported and several of them have advanced into clinical trials. In this brief review, we outline recent progress made in understanding the role of the α7 nAChR in multiple neuropsychiatric disorders and the pharmacological effects of α7 nAChR modulators used in clinical trials.

  5. α7-nAChR Knockout Mice Decreases Biliary Hyperplasia and Liver Fibrosis in Cholestatic Bile-Duct Ligated Mice.

    Science.gov (United States)

    Ehrlich, Laurent; O'Brien, April; Hall, Chad; White, Tori; Chen, Lixian; Wu, Nan; Venter, Julie; Scrushy, Marinda; Mubarak, Muhammad; Meng, Fanyin; Dostal, David; Wu, Chaodong; Lairmore, Terry C; Alpini, Gianfranco; Glaser, Shannon

    2018-03-26

    α7-nAChR is a nicotinic acetylcholine receptor (specifically expressed on hepatic stellate cells, Kupffer cells, and cholangiocytes) that regulates inflammation and apoptosis in the liver. Thus, targeting α7-nAChR may be therapeutic in biliary diseases. Bile-duct ligation (BDL) was performed on wild-type (WT) and α7-nAChR-/- mice. We first evaluated the expression of α7-nAChR by immunohistochemistry (IHC) in liver sections. IHC was also performed to assess intrahepatic bile-duct mass (IBDM), and Sirius Red staining was performed to quantify the amount of collagen deposition. Immunofluorescence was performed to assess co-localization of α7-nAChR with bile ducts (co-stained with CK-19) and hepatic stellate cells (HSCs) (co-stained with desmin). The mRNA expression of α7-nAChR, Ki67/PCNA (proliferation), fibrosis genes (TGF-β1, Fibronectin-1, Col1α1, and α-SMA), and inflammatory markers (IL-6, IL-1β, and TNFα) was measured by real-time PCR. Biliary TGF-β1 and hepatic CD68 (Kupffer cell marker) expression was assessed using IHC. α7-nAChR immunoreactivity was observed in both bile ducts and HSCs and increased following BDL. α7-nAChR-/- BDL mice exhibited decreased: (i) bile duct mass, liver fibrosis, and inflammation; and (ii) immunoreactivity of TGF-1 as well as expression of fibrosis genes compared to WT BDL mice. α7-nAChR activation triggers biliary proliferation and liver fibrosis and may be a therapeutic target in managing extra-hepatic biliary obstruction.

  6. Hypnotherapy for irritable bowel syndrome: an audit of one thousand adult patients.

    Science.gov (United States)

    Miller, V; Carruthers, H R; Morris, J; Hasan, S S; Archbold, S; Whorwell, P J

    2015-05-01

    Gut-focused hypnotherapy improves the symptoms of irritable bowel syndrome (IBS) with benefits being sustained for many years. Despite this, the technique has not been widely adopted by healthcare systems, possibly due to relatively small numbers in published studies and uncertainty about how it should be provided. To review the effect of hypnotherapy in a large cohort of refractory IBS patients. One thousand IBS patients fulfilling Rome II criteria, mean age 51.6 years (range 17-91 years), 80% female, receiving 12 sessions of hypnotherapy over 3 months, were studied. The primary outcome was a 50 point reduction in the IBS Symptom Severity Score. The fall in scores for Noncolonic Symptoms, Quality of Life and Anxiety or Depression, were secondary outcomes. The Federal Drug Administration's recommended outcome of a 30% or more reduction in abdominal pain was also recorded. Overall, 76% met the primary outcome which was higher in females (females: 80%, males: 62%, P hypnotherapy is an effective intervention for refractory IBS. © 2015 John Wiley & Sons Ltd.

  7. Beyond gut feelings: how the gut microbiota regulates blood pressure.

    Science.gov (United States)

    Marques, Francine Z; Mackay, Charles R; Kaye, David M

    2018-01-01

    Hypertension is the leading risk factor for heart disease and stroke, and is estimated to cause 9.4 million deaths globally every year. The pathogenesis of hypertension is complex, but lifestyle factors such as diet are important contributors to the disease. High dietary intake of fruit and vegetables is associated with reduced blood pressure and lower cardiovascular mortality. A critical relationship between dietary intake and the composition of the gut microbiota has been described in the literature, and a growing body of evidence supports the role of the gut microbiota in the regulation of blood pressure. In this Review, we describe the mechanisms by which the gut microbiota and its metabolites, including short-chain fatty acids, trimethylamine N-oxide, and lipopolysaccharides, act on downstream cellular targets to prevent or contribute to the pathogenesis of hypertension. These effects have a direct influence on tissues such as the kidney, the endothelium, and the heart. Finally, we consider the role of the gut microbiota in resistant hypertension, the possible intergenerational effect of the gut microbiota on blood pressure regulation, and the promising therapeutic potential of gut microbiota modification to improve health and prevent disease.

  8. Building GUTs from strings

    International Nuclear Information System (INIS)

    Aldazabal, G.; Ibanez, L.E.; Uranga, A.M.

    1996-01-01

    We study in detail the structure of Grand Unified Theories derived as the low-energy limit of orbifold four-dimensional strings. To this aim, new techniques for building level-two symmetric orbifold theories are presented. New classes of GUTs in the context of symmetric orbifolds are then constructed. The method of permutation modding is further explored and SO(10) GUTs with both 45- or 54-plets are obtained. SU(5) models are also found through this method. It is shown that, in the context of symmetric orbifold SO(10) GUTs, only a single GUT Higgs, either a 54 or a 45, can be present and it always resides in an order-two untwisted sector. Very restrictive results also hold in the case of SU(5). General properties and selection rules for string GUTs are described. Some of these selection rules forbid the presence of some particular GUT-Higgs couplings which are sometimes used in SUSY-GUT model building. Some semi-realistic string GUT examples are presented and their properties briefly discussed. (orig.)

  9. Citral a fragrance allergen and irritant.

    Science.gov (United States)

    Heydorn, S; Menné, T; Andersen, K E; Bruze, M; Svedman, C; White, I R; Basketter, D A

    2003-07-01

    Citral is a well known contact allergen and a contact irritant. Routine patch testing in the past may have been restricted because of possible irritant (IR) patch test responses. 586 consecutive patients, with hand eczema, were patch tested with a selection of fragrances including citral 2% petrolatum and the European standard series. 28 of the patients showed a positive patch test reaction (+ to +++) to citral and 82 at least 1 IR patch test reaction and no positive patch test reaction to citral. A statistically significant association between a positive patch test reaction to citral and positive patch test reactions to other fragrances compared with IR reactions (n = 82) was established. The difference regarding fragrance history found between those with IR and positive reactions to citral was not significant. Citral could be an allergen and/or irritant, worthy of further more extensive studies.

  10. Differential Cytokine Changes in Patients with Myasthenia Gravis with Antibodies against AChR and MuSK.

    Directory of Open Access Journals (Sweden)

    Vuslat Yilmaz

    Full Text Available Neuromuscular transmission failure in myasthenia gravis (MG is most commonly elicited by autoantibodies (ab to the acetylcholine receptor or the muscle-specific kinase, constituting AChR-MG and MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of cytokines related to various Th subtypes were determined in patients with AChR-MG, MuSK-MG and healthy controls (CON. Peripheral blood mononuclear cells (PBMC were activated in vitro by anti-CD3, and cytokines were quantified in supernatants. In purified blood CD4+ T cells, RNA of various cytokines, Th subtype specific transcription factors and the co-stimulatory molecule, CD40L, were quantified by qRT-PCR. Plasma levels of Th1, Th2 and Th17 related cytokines were overall not significantly different between MG subtypes and CON. By contrast, in vitro stimulated PBMC from MuSK-MG but not AChR-MG patients showed significantly increased secretion of the Th1, Th17 and T follicular helper cell related cytokines, IFN-γ, IL-17A and IL-21. Stimulated expression of IL-4, IL-6, IL-10 and IL-13 was not significantly different. At the RNA level, expression of CD40L by CD4+ T cells was reduced in both AChR-MG and MuSK-MG patients while expression of Th subset related cytokines and transcription factors were normal. Immunosuppression treatment had two effects: First, it reduced levels of IL12p40 in the plasma of AChR-MG and MuSK-MG patients, leaving other cytokine levels unchanged; second, it reduced spontaneous secretion of IFN-γ and increased secretion of IL-6 and IL-10 by cultured PBMC from AChR-MG, but not MuSK-MG patients. We conclude that Th1 and Th17 immune reactions play a role in MuSK-MG. Immunosuppression attenuates the Th1 response in AChR-MG and MuSK-MG, but otherwise modulates immune responses in AChR-MG and Mu

  11. Significance of hair-dye base-induced sensory irritation.

    Science.gov (United States)

    Fujita, F; Azuma, T; Tajiri, M; Okamoto, H; Sano, M; Tominaga, M

    2010-06-01

    Oxidation hair-dyes, which are the principal hair-dyes, sometimes induce painful sensory irritation of the scalp caused by the combination of highly reactive substances, such as hydrogen peroxide and alkali agents. Although many cases of severe facial and scalp dermatitis have been reported following the use of hair-dyes, sensory irritation caused by contact of the hair-dye with the skin has not been reported clearly. In this study, we used a self-assessment questionnaire to measure the sensory irritation in various regions of the body caused by two model hair-dye bases that contained different amounts of alkali agents without dyes. Moreover, the occipital region was found as an alternative region of the scalp to test for sensory irritation of the hair-dye bases. We used this region to evaluate the relationship of sensitivity with skin properties, such as trans-epidermal water loss (TEWL), stratum corneum water content, sebum amount, surface temperature, current perception threshold (CPT), catalase activities in tape-stripped skin and sensory irritation score with the model hair-dye bases. The hair-dye sensitive group showed higher TEWL, a lower sebum amount, a lower surface temperature and higher catalase activity than the insensitive group, and was similar to that of damaged skin. These results suggest that sensory irritation caused by hair-dye could occur easily on the damaged dry scalp, as that caused by skin cosmetics reported previously.

  12. Gut metabolome meets microbiome

    DEFF Research Database (Denmark)

    Lamichhane, Santosh; Sen, Partho; Dickens, Alex M

    2018-01-01

    It is well established that gut microbes and their metabolic products regulate host metabolism. The interactions between the host and its gut microbiota are highly dynamic and complex. In this review we present and discuss the metabolomic strategies to study the gut microbial ecosystem. We...... highlight the metabolic profiling approaches to study faecal samples aimed at deciphering the metabolic product derived from gut microbiota. We also discuss how metabolomics data can be integrated with metagenomics data derived from gut microbiota and how such approaches may lead to better understanding...

  13. Melatonin for the treatment of irritable bowel syndrome.

    Science.gov (United States)

    Siah, Kewin Tien Ho; Wong, Reuben Kong Min; Ho, Khek Yu

    2014-03-14

    Irritable bowel syndrome (IBS) is a common disorder characterized by recurrent abdominal pain or discomfort, in combination with disturbed bowel habits in the absence of identifiable organic cause. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone produced by the pineal gland and also large number by enterochromaffin cells of the digestive mucosa. Melatonin plays an important part in gastrointestinal physiology which includes regulation of gastrointestinal motility, local anti-inflammatory reaction as well as moderation of visceral sensation. Melatonin is commonly given orally. It is categorized by the United States Food and Drug Administration as a dietary supplement. Melatonin treatment has an extremely wide margin of safety though it may cause minor adverse effects, such as headache, rash and nightmares. Melatonin was touted as a potential effective candidate for IBS treatment. Putative role of melatonin in IBS treatment include analgesic effects, regulator of gastrointestinal motility and sensation to sleep promoter. Placebo-controlled studies in melatonin suffered from heterogeneity in methodology. Most studies utilized 3 mg at bedtime as the standard dose of trial. However, all studies had consistently showed improvement in abdominal pain, some showed improvement in quality of life of IBS patients. Melatonin is a relatively safe drug that possesses potential in treating IBS. Future studies should focus on melatonin effect on gut mobility as well as its central nervous system effect to elucidate its role in IBS patients.

  14. Dysbiosis of the gut microbiota in disease

    Directory of Open Access Journals (Sweden)

    Simon Carding

    2015-02-01

    Full Text Available There is growing evidence that dysbiosis of the gut microbiota is associated with the pathogenesis of both intestinal and extra-intestinal disorders. Intestinal disorders include inflammatory bowel disease, irritable bowel syndrome (IBS, and coeliac disease, while extra-intestinal disorders include allergy, asthma, metabolic syndrome, cardiovascular disease, and obesity.In many of these conditions, the mechanisms leading to disease development involves the pivotal mutualistic relationship between the colonic microbiota, their metabolic products, and the host immune system. The establishment of a ‘healthy’ relationship early in life appears to be critical to maintaining intestinal homeostasis. Whilst we do not yet have a clear understanding of what constitutes a ‘healthy’ colonic microbiota, a picture is emerging from many recent studies identifying particular bacterial species associated with a healthy microbiota. In particular, the bacterial species residing within the mucus layer of the colon, either through direct contact with host cells, or through indirect communication via bacterial metabolites, may influence whether host cellular homeostasis is maintained or whether inflammatory mechanisms are triggered. In addition to inflammation, there is some evidence that perturbations in the gut microbiota is involved with the development of colorectal cancer. In this case, dysbiosis may not be the most important factor, rather the products of interaction between diet and the microbiome. High-protein diets are thought to result in the production of carcinogenic metabolites from the colonic microbiota that may result in the induction of neoplasia in the colonic epithelium.Ever more sensitive metabolomics methodologies reveal a suite of small molecules produced in the microbiome which mimic or act as neurosignallers or neurotransmitters. Coupled with evidence that probiotic interventions may alter psychological endpoints in both humans and in

  15. Sensory irritation and multiple chemical sensitivity.

    Science.gov (United States)

    Anderson, R C; Anderson, J H

    1999-01-01

    Many of the symptoms described in Sick Building Syndrome (SBS) and multiple chemical sensitivity (MCS) resemble the symptoms known to be elicited by airborne irritant chemicals. Irritation of the eye, nose, and throat is common to SBS, MCS, and sensory irritation (SI). Difficulty of breathing is often seen with SBS, MCS, and pulmonary irritation (PI). We therefore asked the question: can indoor air pollutants cause SI and/or PI? In laboratory testing in which mice breathed the dilute volatile emissions of air fresheners, fabric softeners, colognes, and mattresses for 1 h, we measured various combinations of SI and PI as well as airflow decreases (analogous to asthma attacks). Air samples taken from sites associated with repeated human complaints of poor air quality also caused SI, PI, and airflow limitation (AFL) in the mice. In previous publications, we have documented numerous behavior changes in mice (which we formally studied with a functional observational battery) after exposure to product emissions or complaint site air; neurological complaints are a prominent part of SBS and MCS. All together, these data suggest that many symptoms of SBS and MCS can be described as SI, PI, AFL, and neurotoxicity. All these problems can be caused by airborne irritant chemicals such as those emitted by common commercial products and found in polluted indoor air. With some chemical mixtures (e.g., emissions of some fabric softeners, disposable diapers, and vinyl mattress covers) but not others (e.g., emissions of a solid air freshener), the SI response became larger (2- to 4-fold) when we administered a series of two or three 1-h exposures over a 24-h period. Since with each exposure the intensity of the stimulus was constant yet the magnitude of the response increased, we concluded that there was a change in the sensitivity of the mice to these chemicals. The response was not a generalized stress response because it occurred with only some mixtures of irritants and not others

  16. Reciprocal activation of α5-nAChR and STAT3 in nicotine-induced human lung cancer cell proliferation.

    Science.gov (United States)

    Zhang, Yao; Jia, Yanfei; Li, Ping; Li, Huanjie; Xiao, Dongjie; Wang, Yunshan; Ma, Xiaoli

    2017-07-20

    Cigarette smoking is the top environmental risk factor for lung cancer. Nicotine, the addictive component of cigarettes, induces lung cancer cell proliferation, invasion and migration via the activation of nicotinic acetylcholine receptors (nAChRs). Genome-wide association studies (GWAS) show that CHRNA5 gene encoding α5-nAChR is especially relevant to lung cancer. However, the mechanism of this subunit in lung cancer is not clear. In the present study, we demonstrate that the expression of α5-nAChR is correlated with phosphorylated STAT3 (pSTAT3) expression, smoking history and lower survival of non-small cell lung cancer (NSCLC) samples. Nicotine increased the levels of α5-nAChR mRNA and protein in NSCLC cell lines and activated the JAK2/STAT3 signaling cascade. Nicotine-induced activation of JAK2/STAT3 signaling was inhibited by the silencing of α5-nAChR. Characterization of the CHRNA5 promoter revealed four STAT3-response elements. ChIP assays confirmed that the CHRNA5 promoter contains STAT3 binding sites. By silencing STAT3 expression, nicotine-induced upregulation of α5-nAChR was suppressed. Downregulation of α5-nAChR and/or STAT3 expression inhibited nicotine-induced lung cancer cell proliferation. These results suggest that there is a feedback loop between α5-nAChR and STAT3 that contributes to the nicotine-induced tumor cell proliferation, which indicates that α5-nAChR is an important therapeutic target involved in tobacco-associated lung carcinogenesis. Copyright © 2017 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

  17. A human gut phage catalog correlates the gut phageome with type 2 diabetes.

    Science.gov (United States)

    Ma, Yingfei; You, Xiaoyan; Mai, Guoqin; Tokuyasu, Taku; Liu, Chenli

    2018-02-01

    Substantial efforts have been made to link the gut bacterial community to many complex human diseases. Nevertheless, the gut phages are often neglected. In this study, we used multiple bioinformatic methods to catalog gut phages from whole-community metagenomic sequencing data of fecal samples collected from both type II diabetes (T2D) patients (n = 71) and normal Chinese adults (n = 74). The definition of phage operational taxonomic units (pOTUs) and identification of large phage scaffolds (n = 2567, ≥ 10 k) revealed a comprehensive human gut phageome with a substantial number of novel sequences encoding genes that were unrelated to those in known phages. Interestingly, we observed a significant increase in the number of gut phages in the T2D group and, in particular, identified 7 pOTUs specific to T2D. This finding was further validated in an independent dataset of 116 T2D and 109 control samples. Co-occurrence/exclusion analysis of the bacterial genera and pOTUs identified a complex core interaction between bacteria and phages in the human gut ecosystem, suggesting that the significant alterations of the gut phageome cannot be explained simply by co-variation with the altered bacterial hosts. Alterations in the gut bacterial community have been linked to the chronic disease T2D, but the role of gut phages therein is not well understood. This is the first study to identify a T2D-specific gut phageome, indicating the existence of other mechanisms that might govern the gut phageome in T2D patients. These findings suggest the importance of the phageome in T2D risk, which warrants further investigation.

  18. Gas Chromatography, GC/Mass Analysis and Bioactivity of Essential Oil from Aerial Parts of Ferulago trifida: Antimicrobial, Antioxidant, AChE Inhibitory, General Toxicity, MTT Assay and Larvicidal Activities.

    Science.gov (United States)

    Tavakoli, Saeed; Vatandoost, Hassan; Zeidabadinezhad, Reza; Hajiaghaee, Reza; Hadjiakhoondi, Abbas; Abai, Mohammad Reza; Yassa, Narguess

    2017-09-01

    We aimed to investigate different biological properties of aerial parts essential oil of Ferulago trifida Boiss and larvicidal activity of its volatile oils from all parts of plant. Essential oil was prepared by steam distillation and analyzed by Gas chromatography and GC/Mass. Antioxidant, antimicrobial, cytotoxic effects and AChE inhibitory of the oil were investigated using DPPH, disk diffusion method, MTT assay and Ellman methods. Larvicidal activity of F. trifida essential oil against malaria vector Anopheles stephensi was carried out according to the method described by WHO. In GC and GC/MS analysis, 58 compounds were identified in the aerial parts essential oil, of which E-verbenol (9.66%), isobutyl acetate (25.73%) and E-β-caryophyllene (8.68%) were main compounds. The oil showed (IC 50 = 111.2μg/ml) in DPPH and IC 50 = 21.5 mg/ml in the investigation of AChE inhibitory. Furthermore, the oil demonstrated toxicity with (LD 50 = 1.1μg/ml) in brine shrimp lethality test and with (IC 50 = 22.0, 25.0 and 42.55 μg/ml) on three cancerous cell lines (MCF-7, A-549 and HT-29) respectively. LC 50 of stem, root, aerial parts, fruits, and flowers essential oils against larvae of An. stephensi were equal with 10.46, 22.27, 20.50, 31.93 and 79.87ppm respectively. In antimicrobial activities, essential oil was effective on all specimens except Escherichia coli , Aspergillus niger and Candida albicans. The essential oil showed moderate antioxidant activity, strong antimicrobial properties and good toxic effect in brine shrimp test and MTT assay on three cancerous cell lines.

  19. Diet, gut microbiota and cognition.

    Science.gov (United States)

    Proctor, Cicely; Thiennimitr, Parameth; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2017-02-01

    The consumption of a diet high in fat and sugar can lead to the development of obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease and cognitive decline. In the human gut, the trillions of harmless microorganisms harboured in the host's gastrointestinal tract are called the 'gut microbiota'. Consumption of a diet high in fat and sugar changes the healthy microbiota composition which leads to an imbalanced microbial population in the gut, a phenomenon known as "gut dysbiosis". It has been shown that certain types of gut microbiota are linked to the pathogenesis of obesity. In addition, long-term consumption of a high fat diet is associated with cognitive decline. It has recently been proposed that the gut microbiota is part of a mechanistic link between the consumption of a high fat diet and the impaired cognition of an individual, termed "microbiota-gut-brain axis". In this complex relationship between the gut, the brain and the gut microbiota, there are several types of gut microbiota and host mechanisms involved. Most of these mechanisms are still poorly understood. Therefore, this review comprehensively summarizes the current evidence from mainly in vivo (rodent and human) studies of the relationship between diet, gut microbiota and cognition. The possible mechanisms that the diet and the gut microbiota have on cognition are also presented and discussed.

  20. Acetylcholine serves as a derepressor in Loperamide-induced Opioid-Induced Bowel Dysfunction (OIBD) in zebrafish.

    Science.gov (United States)

    Shi, Yanyan; Zhang, Yu; Zhao, Fangying; Ruan, Hua; Huang, Honghui; Luo, Lingfei; Li, Li

    2014-07-07

    The mechanisms underlying gut development, especially peristalsis, are widely studied topics. However, the causes of gut peristalsis-related diseases, especially Opioid-Induced Bowel Dysfunction (OIBD) disorder, have not been well defined. Therefore, our study used zebrafish, a popular model for studying both gut development and peristalsis, and DCFH-DA, a dye that clearly labels the live fish gut lumen, to characterize the formation process of gut lumen as well as the gut movement style in vivo. By applying Loperamide Hydrochloride (LH), the μ-opioid receptor-specific agonist, we established an OIBD-like zebrafish model. Our study found that acetylcholine (ACh) was a key transmitter that derepressed the phenotype induced by LH. Overall, the study showed that the antagonistic role of ACh in the LH-mediated opioid pathway was evolutionarily conserved; moreover, the OIBD-like zebrafish model will be helpful in the future dissection of the molecular pathways involved in gut lumen development and pathology.

  1. OP-16 DIETARY INTERVENTION USING THE LOW FODMAP DIET VERSUS THE "MILK, EGG, WHEAT AND SOYA FREE" DIET FOR TREATMENT OF FUNCTIONAL GUT DISORDERS A SINGLE CENTRE EXPERIENCE.

    Science.gov (United States)

    Keetarut, K; Kiparissi, F; McCartney, S; Murray, C

    2015-10-01

    The adolescent clinic is a tertiary referral clinic including patients with a wide variety of complex gastroenterology conditions predominantly tertiary referrals fromGreat Ormond Street Hospital transition clinic. To assess the benefit of the low FODMAP diet versus the "Milk, egg, wheat and soya" (MEWS) free diet for symptom control in patients with functional gut disorders and/or food allergy from June 2013 to June 2015. A total of 436 patients were seen during this time period for dietetic advice and the age range varied from 13-21 years old with 43terms of diagnosis used. These included the broad categories of inflammatory bowel disease, food allergy, functional gut conditions, congenital gut disorders, autoimmune disorders and oncology conditions. For functional gut disorders/food allergy there were 14 terms used which varied from "Functional gut disorder" to "Irritable bowel syndrome" and also included patients with delayed gastric emptying. For patients with food allergy the terms "multiple food allergy" or EosinophilicOesophagitis or Colitis were used. A total of 40 patients with functional gut disorders were referred for the MEWS or low FODMAP diet. The efficacy of the diet was measured using a symptom scale pre and post dietary intervention assessing if patients symptoms changed from nil/mild/moderate tosignificant. The results indicate whether the presenting predominant symptom e.g., bloating, constipation or abdominal pain improved following the dietary intervention. A total of 29 patients were seen for the "MEWS" free diet.These were 17 functional, 3 food allergy, 6 IBS, 2 EosinophilicOesophagitis, 1 oncology patient. The age ranged from 14 to 21 and average ageat treatment was 16.6 years old with 11 males and 18 females. 13 patients were referred for the low FODMAP diet. The patients referred for the low FODMAP diet were 7 with a functional gut disorder, 5Irritable Bowel Syndrome and1 EosinophilicColitis.The age range was 14 to 19 years old with

  2. Menthol Enhances Nicotine Reward-Related Behavior by Potentiating Nicotine-Induced Changes in nAChR Function, nAChR Upregulation, and DA Neuron Excitability.

    Science.gov (United States)

    Henderson, Brandon J; Wall, Teagan R; Henley, Beverley M; Kim, Charlene H; McKinney, Sheri; Lester, Henry A

    2017-11-01

    Understanding why the quit rate among smokers of menthol cigarettes is lower than non-menthol smokers requires identifying the neurons that are altered by nicotine, menthol, and acetylcholine. Dopaminergic (DA) neurons in the ventral tegmental area (VTA) mediate the positive reinforcing effects of nicotine. Using mouse models, we show that menthol enhances nicotine-induced changes in nicotinic acetylcholine receptors (nAChRs) expressed on midbrain DA neurons. Menthol plus nicotine upregulates nAChR number and function on midbrain DA neurons more than nicotine alone. Menthol also enhances nicotine-induced changes in DA neuron excitability. In a conditioned place preference (CPP) assay, we observed that menthol plus nicotine produces greater reward-related behavior than nicotine alone. Our results connect changes in midbrain DA neurons to menthol-induced enhancements of nicotine reward-related behavior and may help explain how smokers of menthol cigarettes exhibit reduced cessation rates.

  3. Gut Protozoa: Friends or Foes of the Human Gut Microbiota?

    Science.gov (United States)

    Chabé, Magali; Lokmer, Ana; Ségurel, Laure

    2017-12-01

    The importance of the gut microbiota for human health has sparked a strong interest in the study of the factors that shape its composition and diversity. Despite the growing evidence suggesting that helminths and protozoa significantly interact with gut bacteria, gut microbiome studies remain mostly focused on prokaryotes and on populations living in industrialized countries that typically have a low parasite burden. We argue that protozoa, like helminths, represent an important factor to take into account when studying the gut microbiome, and that their presence - especially considering their long coevolutionary history with humans - may be beneficial. From this perspective, we examine the relationship between the protozoa and their hosts, as well as their relevance for public health. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Occupational irritant contact dermatitis due to petroleum naphtha

    Directory of Open Access Journals (Sweden)

    Aslı Aytekin

    2014-12-01

    Full Text Available Irritant contact dermatitis (ICD is responsible for the vast majority of occupational contact dermatitis and usually seen in professional groups working with wet hand. However, today, with the increasing business lines, employees are exposed to a variety of irritants. Occupational exposure to many chemicals and toxic irritants affect not only the skin, but also the other systems. Therefore, this situation resulting with loss of work and changes in business may become a public health problem. The diagnosis of occupational contact dermatitis should not be limited only with tests for allergens, detailed history of exposure to workplace substances and careful examination of product safety forms are necessary. In addition, by establishing close relationship between occupational physicians and employers, preventive measures should be taken before similar diseases occur in other workers in the same work place. In order to highlight this issue, a 32-year-old male patient working in an invitation card fabric is presented in this case report. Irritant contact dermatitis secondary to “petroleum naphta” was present in the patient’s arms. Another important feature of this case, as far as we know, this is the first case of irritant contact dermatitis due to naphtha in the literature.

  5. The Relationship between Irritable Bowel Syndrome, Depression, Anxiety, and Stress among Sample of Irritable Bowel Patients - Predictive Study

    OpenAIRE

    Osama Hasan Gaber

    2016-01-01

    This study aimed to examine the relationship of irritable bowel syndrome, anxiety, depression and stress among a sample of78 IBS patients (Rome III Diagnostic Criteria for Irritable Bowel Syndrome), anxiety symptoms scale, Depression symptoms scale, and stress scale (prepared by the researcher) were used Pearson Correlation Coefficient showed that there are statistically significant relationship between IBS and Anxiety, Depression and Stress (P?=0.01). The Regression and Prediction Coefficien...

  6. Concomitant alpha7 and beta2 nicotinic AChR subunit deficiency leads to impaired energy homeostasis and increased physical activity in mice.

    Science.gov (United States)

    Somm, Emmanuel; Guérardel, Audrey; Maouche, Kamel; Toulotte, Audrey; Veyrat-Durebex, Christelle; Rohner-Jeanrenaud, Françoise; Maskos, Uwe; Hüppi, Petra S; Schwitzgebel, Valérie M

    2014-05-01

    Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated cation channels well characterized in neuronal signal transmission. Moreover, recent studies have revealed nAChR expression in nonneuronal cell types throughout the body, including tissues involved in metabolism. In the present study, we screen gene expression of nAChR subunits in pancreatic islets and adipose tissues. Mice pancreatic islets present predominant expression of α7 and β2 nAChR subunits but at a lower level than in central structures. Characterization of glucose and energy homeostasis in α7β2nAChR(-/-) mice revealed no major defect in insulin secretion and sensitivity but decreased glycemia apparently unrelated to gluconeogenesis or glycogenolysis. α7β2nAChR(-/-) mice presented an increase in lean and bone body mass and a decrease in fat storage with normal body weight. These observations were associated with elevated spontaneous physical activity in α7β2nAChR(-/-) mice, mainly due to elevation in fine vertical (rearing) activity while their horizontal (ambulatory) activity remained unchanged. In contrast to α7nAChR(-/-) mice presenting glucose intolerance and insulin resistance associated to excessive inflammation of adipose tissue, the present metabolic phenotyping of α7β2nAChR(-/-) mice revealed a metabolic improvement possibly linked to the increase in spontaneous physical activity related to central β2nAChR deficiency. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Gut microbiota and obesity.

    Science.gov (United States)

    Gérard, Philippe

    2016-01-01

    The human intestine harbors a complex bacterial community called the gut microbiota. This microbiota is specific to each individual despite the existence of several bacterial species shared by the majority of adults. The influence of the gut microbiota in human health and disease has been revealed in the recent years. Particularly, the use of germ-free animals and microbiota transplant showed that the gut microbiota may play a causal role in the development of obesity and associated metabolic disorders, and lead to identification of several mechanisms. In humans, differences in microbiota composition, functional genes and metabolic activities are observed between obese and lean individuals suggesting a contribution of the gut microbiota to these phenotypes. Finally, the evidence linking gut bacteria to host metabolism could allow the development of new therapeutic strategies based on gut microbiota modulation to treat or prevent obesity.

  8. Work-associated irritable larynx syndrome.

    Science.gov (United States)

    Anderson, Jennifer A

    2015-04-01

    The purpose of this study is to review the relevant literature concerning work-associated irritable larynx syndrome (WILS), a hyperkinetic laryngeal disorder associated with occupational irritant exposure. Clinical symptoms are variable and include dysphonia, cough, dyspnoea and globus pharyngeus. WILS is a clinical diagnosis and can be difficult to differentiate from asthma. Treatment options for WILS include medical and behavioural therapy. Laryngeal-centred upper airway symptoms secondary to airborne irritants have been documented in the literature under a variety of diagnostic labels, including WILS, vocal cord dysfunction (VCD), laryngeal hypersensitivity and laryngeal neuropathy and many others. The underlying pathophysiology is as yet poorly understood; however, the clinical scenario suggests a multifactorial nature to the disorder. More recent literature indicates that central neuronal plasticity, inflammatory processes and psychological factors are all likely contributors. Possible mechanisms for WILS include central neuronal network plasticity after noxious exposure and/or viral infection, inflammation (i.e. reflux disease) and intrinsic patient factors such a psychological state. Treatment is individualized and frequently includes one or more of the following: environmental changes in the workplace, GERD therapy, behavioural/speech therapy, psychotherapy counselling and neural modifiers.

  9. SO(10) GUT baryogenesis

    International Nuclear Information System (INIS)

    Gu Peihong; Sarkar, Utpal

    2008-01-01

    Baryogenesis, through the decays of heavy bosons, was considered to be one of the major successes of the grand unified theories (GUTs). It was then realized that the sphaleron processes erased any baryon asymmetry from the GUT-baryogenesis at a later stage. In this Letter, we discuss the idea of resurrecting GUT-baryogenesis [M. Fukugita, T. Yanagida, Phys. Rev. Lett. 89 (2002) 131602] in a large class of SO(10) GUTs. Our analysis shows that fast lepton number violating but baryon number conserving processes can partially wash out the GUT-baryogenesis produced lepton and/or baryon asymmetry associated with or without the sphaleron and/or Yukawa interactions

  10. Pharmacological Approach for Managing Pain in Irritable Bowel Syndrome: A Review Article

    Science.gov (United States)

    Chen, Longtu; Ilham, Sheikh J.; Feng, Bin

    2017-01-01

    Context Visceral pain is a leading symptom for patients with irritable bowel syndrome (IBS) that affects 10% - 20 % of the world population. Conventional pharmacological treatments to manage IBS-related visceral pain is unsatisfactory. Recently, medications have emerged to treat IBS patients by targeting the gastrointestinal (GI) tract and peripheral nerves to alleviate visceral pain while avoiding adverse effects on the central nervous system (CNS). Several investigational drugs for IBS also target the periphery with minimal CNS effects. Evidence of Acquisition In this paper, reputable internet databases from 1960 - 2016 were searched including Pubmed and ClinicalTrials.org, and 97 original articles analyzed. Search was performed based on the following keywords and combinations: irritable bowel syndrome, clinical trial, pain, visceral pain, narcotics, opioid, chloride channel, neuropathy, primary afferent, intestine, microbiota, gut barrier, inflammation, diarrhea, constipation, serotonin, visceral hypersensitivity, nociceptor, sensitization, hyperalgesia. Results Certain conventional pain managing drugs do not effectively improve IBS symptoms, including NSAIDs, acetaminophen, aspirin, and various narcotics. Anxiolytic and antidepressant drugs (Benzodiazepines, TCAs, SSRI and SNRI) can attenuate pain in IBS patients with relevant comorbidities. Clonidine, gabapentin and pregabalin can moderately improve IBS symptoms. Lubiprostone relieves constipation predominant IBS (IBS-C) while loperamide improves diarrhea predominant IBS (IBS-D). Alosetron, granisetron and ondansetron can generally treat pain in IBS-D patients, of which alosetron needs to be used with caution due to cardiovascular toxicity. The optimal drugs for managing pain in IBS-D and IBS-C appear to be eluxadoline and linaclotide, respectively, both of which target peripheral GI tract. Conclusions Conventional pain managing drugs are in general not suitable for treating IBS pain. Medications that target

  11. Histological distinction between early allergic and irritant patch test reactions

    DEFF Research Database (Denmark)

    Vestergaard, L; Clemmensen, Ole; Sørensen, Flemming Brandt

    1999-01-01

    no recognizable changes except a slight follicular spongiosis in 1 patient. The 2 pathologists agreed independently on the correct classification in 6 out of 7 cases (p=0.0156). We tested an optimized model, selecting non-irritant allergens and a well-known irritant. Further investigations are needed to elucidate......Comparative light microscopic studies have revealed subtle differences between allergic and irritant reactions in the skin. In the search for specific differences, we focussed on the early inflammatory response. This pilot study was conducted to test the hypothesis that follicular spongiosis can...... differentiate between early allergic and irritant patch test reactions. 8 patients with known contact allergy to either colophony or quarternium-15 participated in the study. In each patient, allergic and irritant patch tests reactions were elicited, and 4-mm punch biopsies were taken after 6 8 h from...

  12. Stress-Related Alterations of Visceral Sensation: Animal Models for Irritable Bowel Syndrome Study

    Science.gov (United States)

    Mulak, Agata; Taché, Yvette

    2011-01-01

    Stressors of different psychological, physical or immune origin play a critical role in the pathophysiology of irritable bowel syndrome participating in symptoms onset, clinical presentation as well as treatment outcome. Experimental stress models applying a variety of acute and chronic exteroceptive or interoceptive stressors have been developed to target different periods throughout the lifespan of animals to assess the vulnerability, the trigger and perpetuating factors determining stress influence on visceral sensitivity and interactions within the brain-gut axis. Recent evidence points towards adequate construct and face validity of experimental models developed with respect to animals' age, sex, strain differences and specific methodological aspects such as non-invasive monitoring of visceromotor response to colorectal distension as being essential in successful identification and evaluation of novel therapeutic targets aimed at reducing stress-related alterations in visceral sensitivity. Underlying mechanisms of stress-induced modulation of visceral pain involve a combination of peripheral, spinal and supraspinal sensitization based on the nature of the stressors and dysregulation of descending pathways that modulate nociceptive transmission or stress-related analgesic response. PMID:21860814

  13. Gas Chromatography, GC/Mass Analysis and Bioactivity of Essential Oil from Aerial Parts of Ferulago trifida: Antimicrobial, Antioxidant, AChE Inhibitory, General Toxicity, MTT assay and Larvicidal Activities

    Directory of Open Access Journals (Sweden)

    Saeed Tavakoli

    2017-10-01

    Full Text Available Background: We aimed to investigate different biological properties of aerial parts essential oil of Ferulago trifida Boiss and larvicidal activity of its volatile oils from all parts of plant.Methods: Essential oil was prepared by steam distillation and analyzed by Gas chromatography and GC/Mass. Anti­oxidant, antimicrobial, cytotoxic effects and AChE inhibitory of the oil were investigated using DPPH, disk diffusion method, MTT assay and Ellman methods. Larvicidal activity of F. trifida essential oil against malaria vector Anoph­eles stephensi was carried out according to the method described by WHO.Results: In GC and GC/MS analysis, 58 compounds were identified in the aerial parts essential oil, of which E-ver­benol (9.66%, isobutyl acetate (25.73% and E-β-caryophyllene (8.68% were main compounds. The oil showed (IC50= 111.2µg/ml in DPPH and IC50= 21.5 mg/ml in the investigation of AChE inhibitory. Furthermore, the oil demonstrated toxicity with (LD50= 1.1µg/ml in brine shrimp lethality test and with (IC50= 22.0, 25.0 and 42.55 µg/ml on three cancerous cell lines (MCF-7, A-549 and HT-29 respectively. LC50 of stem, root, aerial parts, fruits, and flowers essential oils against larvae of An. stephensi were equal with 10.46, 22.27, 20.50, 31.93 and 79.87ppm respectively. In antimicrobial activities, essential oil was effective on all specimens except Escherichia coli, Asper­gillus niger and Candida albicans.Conclusion: The essential oil showed moderate antioxidant activity, strong antimicrobial properties and good toxic effect in brine shrimp test and MTT assay on three cancerous cell lines.

  14. Respiratory irritation by trimellitic anhydride in Brown Norway and Wistar rats

    NARCIS (Netherlands)

    Arts, J.H.E.; Koning, M.W.de; Bloksma, N.; Kuper, C.F.

    2001-01-01

    Several acid anhydrides are known for their sensitizing and irritative properties. Since both irritation and respiratory allergy can cause changes of lung function, proper testing of allergen-dependent effects on the respiratory tract requires knowledge of the respiratory irritant effects. To study

  15. SUSY GUT Model Building

    International Nuclear Information System (INIS)

    Raby, Stuart

    2008-01-01

    In this talk I discuss the evolution of SUSY GUT model building as I see it. Starting with 4 dimensional model building, I then consider orbifold GUTs in 5 dimensions and finally orbifold GUTs embedded into the E 8 xE 8 heterotic string.

  16. Potential allergy and irritation incidents among health care workers.

    Science.gov (United States)

    Alamgir, Hasanat; Yu, Shicheng; Chavoshi, Negar; Ngan, Karen

    2008-07-01

    This study describes the types, causes, and outcomes of potential irritation and allergy incidents among workers in British Columbia's health care industry. Data on occupation-induced allergy and irritation incidents were extracted from a standardized database using the number of productive hours obtained from payroll data as a denominator during a 1-year period from three British Columbia health regions. Younger workers, female workers, facility support service workers, laboratory assistants and technicians, and maintenance and acute care workers were found to be at higher risk for allergy and irritation incidents. Major causes of allergy and irritation incidents included chemicals, blood and body fluids, food and objects, communicable diseases, air quality, and latex. A larger proportion of chemically induced incidents resulted in first aid care only, whereas non-chemical incidents required more emergency room visits.

  17. Targeting α4β2 nAChRs in CNS disorders: Perspectives on positive allosteric modulation as a therapeutic approach

    DEFF Research Database (Denmark)

    Grupe, Morten; Grunnet, Morten; Bastlund, Jesper F.

    2015-01-01

    The nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels broadly involved in regulating neurotransmission in the central nervous system (CNS) by conducting cation currents through the membrane of neurons. Many different nAChR subtypes exist with each their functional character......The nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels broadly involved in regulating neurotransmission in the central nervous system (CNS) by conducting cation currents through the membrane of neurons. Many different nAChR subtypes exist with each their functional...... characteristics, expression pattern and pharmacological profile. The focus of the present MiniReview is on the heteromeric α4β2 nAChR, as activity at this subtype contributes to cognitive functioning through interactions with multiple neurotransmitter systems and is implicated in various CNS disorders...... and temporal aspects of neurotransmission as well as higher subtype selectivity, hypothetically resulting in high clinical efficacy with minimal adverse effects. In this MiniReview, we describe the currently identified compounds, which potentiate the effects of agonists at the α4β2 nAChR. The potential...

  18. Gancao-Gansui combination impacts gut microbiota diversity and related metabolic functions.

    Science.gov (United States)

    Yu, Jingao; Guo, Jianming; Tao, Weiwei; Liu, Pei; Shang, Erxin; Zhu, Zhenhua; Fan, Xiuhe; Shen, Juan; Hua, Yongqing; Zhu, Kevin Yue; Tang, Yuping; Duan, Jin-Ao

    2018-03-25

    The theory of "eighteen incompatible medicaments" (EIM) in traditional Chinese medicine (TCM) is the most representative case of herbal-herbal interactions. Gancao and Gansui are one of the incompatible herbal pairs in EIM. Gancao, also known as "licorice", is the most frequently used Chinese herb or food additive. Gansui, the root of Euphorbia kansui T.P. Wang, is another famous Chinese herb usually used to treat edema, ascites and asthma but could induce gastrointestinal (GI) tract irritation. Although Gancao and Gansui are incompatible herbal pairs, they are still used in combination in the famous "Gansui-Banxia" decoction. This study was conducted to investigate if Gancao-Gansui combination could exacerbate Gansui induced GI tract injury. Moreover, the impact of Gancao-Gansui combination to gut microbiota and related metabolism pathways were evaluated. Normal mice were divided into different groups and treated with Gancao extracts, Gansui extracts, and Gancao-Gansui combination extracts for 7 days. Serum biomarkers (diamine oxidase activity, lipopolysaccharide, motilin, IL-1β, IL-6, TNF-α) were determined to reflect GI tract damage. Gut microbiota diversity was studied by 16S rDNA sequencing and metagenomes analysis were also conducted to reflect functional genes expression alteration. Fecal hydrogen sulfide concentrations were measured by spectrophotometry to confirm the alteration of Desulfovibrio genus. Fecal lipid metabolomics study was conducted by GC-MS analysis to confirm the change of metagenomes and Mycoplasma abundance. Gancao-Gansui combination did not exacerbate GI tract tissue or functional damage but caused gut microbiota dysbiosis and increased some rare genus's abundance including Desulfovibrio and Mycoplasma. Desulfovibrio genus proliferation was confirmed by the disturbance of fecal hydrogen sulfide homeostasis. Gancao-Gansui combination also dys-regulated the metabolic genes in metagenomes. Mycoplasma genus proliferation and the metagenomes

  19. Effect of maternal probiotic intervention on HPA axis, immunity and gut microbiota in a rat model of irritable bowel syndrome.

    Directory of Open Access Journals (Sweden)

    Javad Barouei

    Full Text Available OBJECTIVE: To examine whether maternal probiotic intervention influences the alterations in the brain-immune-gut axis induced by neonatal maternal separation (MS and/or restraint stress in adulthood (AS in Wistar rats. DESIGN: Dams had free access to drinking water supplemented with Bifidobacterium animalis subsp lactis BB-12® (3 × 10(9 CFU/mL and Propionibacterium jensenii 702 (8.0 × 10(8 CFU/mL from 10 days before conception until postnatal day (PND 22 (weaning day, or to control ad lib water. Offspring were subjected to MS from PND 2 to 14 or left undisturbed. From PND 83 to 85, animals underwent 30 min/day AS, or were left undisturbed as controls. On PND 24 and 86, blood samples were collected for corticosterone, ACTH and IgA measurement. Colonic contents were analysed for the composition of microflora and luminal IgA levels. RESULTS: Exposure to MS significantly increased ACTH levels and neonatal fecal counts of aerobic and anaerobic bacteria, E. coli, enterococci and clostridia, but reduced plasma IgA levels compared with non-MS animals. Animals exposed to AS exhibited significantly increased ACTH and corticosterone levels, decreased aerobic bacteria and bifidobacteria, and increased Bacteroides and E. coli counts compared to non-AS animals. MS coupled with AS induced significantly decreased anaerobes and clostridia compared with the non-stress adult controls. Maternal probiotic intervention significantly increased neonatal corticosterone levels which persisted until at least week 12 in females only, and also resulted in elevated adult ACTH levels and altered neonatal microflora comparable to that of MS. However, it improved plasma IgA responses, increased enterococci and clostridia in MS adults, increased luminal IgA levels, and restored anaerobes, bifidobacteria and E. coli to normal in adults. CONCLUSION: Maternal probiotic intervention induced activation of neonatal stress pathways and an imbalance in gut microflora. Importantly

  20. Calcium imaging with genetically encoded sensor Case12: Facile analysis of α7/α9 nAChR mutants.

    Directory of Open Access Journals (Sweden)

    Irina Shelukhina

    Full Text Available Elucidation of the structural basis of pharmacological differences for highly homologous α7 and α9 nicotinic acetylcholine receptors (nAChRs may shed light on their involvement in different physiological functions and diseases. Combination of site-directed mutagenesis and electrophysiology is a powerful tool to pinpoint the key amino-acid residues in the receptor ligand-binding site, but for α7 and α9 nAChRs it is complicated by their poor expression and fast desensitization. Here, we probed the ligand-binding properties of α7/α9 nAChR mutants by a proposed simple and fast calcium imaging method. The method is based on transient co-expression of α7/α9 nAChR mutants in neuroblastoma cells together with Ric-3 or NACHO chaperones and Case12 fluorescent calcium ion sensor followed by analysis of their pharmacology using a fluorescence microscope or a fluorometric imaging plate reader (FLIPR with a GFP filter set. The results obtained were confirmed by electrophysiology and by calcium imaging with the conventional calcium indicator Fluo-4. The affinities for acetylcholine and epibatidine were determined for human and rat α7 nAChRs, and for their mutants with homologous residues of α9 nAChR incorporated at positions 117-119, 184, 185, 187, and 189, which are anticipated to be involved in ligand binding. The strongest decrease in the affinity was observed for mutations at positions 187 and 119. The L119D mutation of α7 nAChR, showing a larger effect for epibatidine than for acetylcholine, may implicate this position in pharmacological differences between α7 and α9 nAChRs.

  1. The determination of the irritancy potential of surfactants using various methods of assessment.

    Science.gov (United States)

    Ciuchta, H P; Dodd, K T

    1978-01-01

    Several animal irritancy test methods whose criteria include sensory response, pain/discomfort or tissue damage were evaluated as to their ability to assess relative irritancy potential of the following surfactants: sodium lauryl polyether (12) sulfate (SLES), Miranol C2M (MC2M), Miranol MHT (MMHT), sodium coco methyl tauride (SCMT), triethanolamine lauryl sulfate (TEALS), ammonium lauryl sulfate (ALS) and sodium lauryl sulfate (SLS). Data from the mouse upper respiratory tract and mouse writhing tests indicated that SLES, MC2M and MMHT were the least irritating and SLS, ALS and TEALS were the most irritating. The blepharospasm test did not lend itself to this type of evaluation because sequential instillation of the surfactants produced eye anesthesia. Data from the Draize eye test indicated that SLES was the least irritating while MC2M was slightly more irritating. All other surfactants were equally irritating. The Draize skin test results showed that SLES again was the least irritating at all concentrations tested and that SLS and ALS along with TEALS and SCMT were the most irritating.

  2. Synthesis and DPPH scavenging assay of reserpine analogues, computational studies and in silico docking studies in AChE and BChE responsible for Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Muhammad Yar

    2015-03-01

    Full Text Available Alzheimer's disease (AD is a fast growing neurodegenerative disorder of the central nervous system and anti-oxidants can be used to help suppress the oxidative stress caused by the free radicals that are responsible for AD. A series of selected synthetic indole derivatives were biologically evaluated to identify potent new antioxidants. Most of the evaluated compounds showed significant to modest antioxidant properties (IC50 value 399.07 140.0±50 µM. Density Functional Theory (DFT studies were carried out on the compounds and their corresponding free radicals. Differences in the energy of the parent compounds and their corresponding free radicals provided a good justification for the trend found in their IC50 values. In silico, docking of compounds into the proteins acetylcholinesterase (AChE and butyrylcholinesterase (BChE, which are well known for contributing in AD disease, was also performed to predict anti-AD potential.

  3. Pros and Cons While Looking Through an Asian Window on the Rome IV Criteria for Irritable Bowel Syndrome: Pros.

    Science.gov (United States)

    Ghoshal, Uday C

    2017-07-30

    A decade after Rome III, in 2016, Rome IV criteria were published. There are major differences between Rome IV and the earlier iteration, some of which are in line with Asian viewpoints. The clinical applicability of the Rome IV criteria of irritable bowel syndrome (IBS) in Asian perspective is reviewed here. Instead of considering functional gastrointestinal disorders (FGIDs) to be largely psychogenic, Rome IV suggested the importance of the gut over brain ("disorders of gut-brain interaction" not "brain-gut interaction"). The word "functional" is underplayed. Multi-dimensional clinical profile attempts to recognize micro-organic nature, like slow colon transit and fecal evacuation disorders in constipation and dietary intolerance including that of lactose and fructose, bile acid malabsorption, non-celiac wheat sensitivity, small intestinal bacterial overgrowth, and gastrointestinal infection in diarrhea. Overlap between different FGIDs has been recognized as Rome IV suggests these to be a spectrum rather than discrete disorders. Bloating, common in Asia, received attention, though less. Sub-typing of IBS may be more clinician-friendly now as the patient-reported stool form may be used than a diary. However, a few issues, peculiar to Asia, need consideration; Rome IV, like Rome III, suggests that Bristol type I-II stool to denote constipation though Asian experts include type III as well. Work-up for physiological factors should be given greater importance. Language issue is important. Bloating, common in IBS, should be listed in the criteria. Threshold values for symptoms in Rome IV criteria are based on Western data. Post-infectious malabsorption (tropical sprue) should be excluded to diagnose post-infectious IBS, particularly in Asia.

  4. Review article: potential mechanisms of action of rifaximin in the management of irritable bowel syndrome with diarrhoea.

    Science.gov (United States)

    Pimentel, M

    2016-01-01

    The role of gut microbiota in the pathophysiology of irritable bowel syndrome (IBS) is supported by various lines of evidence, including differences in mucosal and faecal microbiota between patients with IBS and healthy individuals, development of post-infectious IBS, and the efficacy of some probiotics and nonsystemic antibiotics (e.g. rifaximin). To review the literature regarding the role of rifaximin in IBS and its potential mechanism(s) of action. A literature search was conducted using the terms 'rifaximin', 'irritable bowel syndrome' and 'mechanism of action'. Rifaximin was approved in 2015 for the treatment of IBS with diarrhoea. In contrast to other currently available IBS therapies that require daily administration to maintain efficacy, 2-week rifaximin treatment achieved symptom improvement that persisted ≥12 weeks post-treatment. The mechanisms of action of rifaximin, therefore, may extend beyond direct bactericidal effects. Data suggest that rifaximin may decrease host proinflammatory responses to bacterial products in patients with IBS. In some cases, small intestinal bacterial overgrowth (SIBO) may play a role in the clinical symptoms of IBS. Because of the high level of solubility of rifaximin in the small intestine, rifaximin may reset microbial diversity in this environment. Consistent with this hypothesis, rifaximin has antibiotic efficacy against isolates derived from patients with SIBO. Resetting microbial diversity via rifaximin use may lead to a decrease in bacterial fermentation and a reduction in the clinical symptoms of IBS. © 2015 John Wiley & Sons Ltd.

  5. The α7-nACh nicotinic receptor and its role in memory and selected diseases of the central nervous system

    Directory of Open Access Journals (Sweden)

    Urszula Baranowska

    2017-07-01

    Full Text Available α7-nACh is one of the major nicotinic cholinergic receptor subtypes found in the brain. It is broadly expressed in the hippocampal and cortical neurons, the regions which play a key role in memory formation. Although α7-nACh receptors may serve as postsynaptic receptors mediating classical neurotransmission, they usually function as presynaptic modulators responsible for the release of other neurotransmitters, such as glutamate, γ-aminobutyric acid, dopamine, and norepinephrine. They can, therefore, affect a wide array of neurobiological functions. In recent years, research has found that a large number of agonists and positive allosteric modulators of α7-nAChR induce beneficial effects on learning and memory. Consistently, mice deficient in chrna7 (the gene encoding α7-nAChR protein, are characterized by memory deficits. In addition, decreased expression and function of α7-nAChR is associated agoniwith many neurological diseases including schizophrenia, bipolar disorder, learning disability, attention deficit hyperactivity disorder, Alzheimer disease, autism, and epilepsy. In the recent years many animal experiments and clinical trials using α7-nAChR ligands were conducted. The results of these studies strongly indicate that agonists and positive allosteric modulators of α7-nAChR are promising therapeutic agents for diseases associated with cognitive deficits.

  6. Additive impairment of the barrier function and irritation by biogenic amines and sodium lauryl sulphate: a controlled in vivo tandem irritation study.

    Science.gov (United States)

    Fluhr, J W; Kelterer, D; Fuchs, S; Kaatz, M; Grieshaber, R; Kleesz, P; Elsner, P

    2005-01-01

    Biogenic amines are potential irritants e.g. in fish-, meat-, milk- and egg-processing professions like cooks, butchers and bakers. The aim of this study was to test the irritative and barrier-disrupting properties of the biogenic amines ammonium hydroxide (AM), dimethylamine (DMA) and trimethylamine (TMA). A repeated sequential irritation of 30 min twice per day was performed over a total of 4 days (tandem repeated irritation test) on the back of 20 healthy volunteers of both sexes with AM, DMA, TMA and sodium lauryl sulphate (SLS). The epidermal barrier function was assessed with a Tewameter TM 210, stratum corneum surface pH was measured with a Skin-pH-Meter 900, inflammation was assessed with a Chromameter CR-300 on the a* axis for redness and a visual score was recorded. All tested biogenic amines (AM, DMA and TMA) induced a barrier disruption and a pH increase paralleled with a 1-day-delayed onset of inflammatory signs. These effects were further enhanced and accelerated by a sequential application of SLS together with the biogenic amines, and inflammation occurred earlier than with the single compounds. Acetic acid (AA) in contrast did only show mild barrier disruption and no significant inflammatory signs. Our system allowed a ranking of the different compounds in their irritative potential in the tandem irritation with SLS: SLS > NaOH > TMA > AA > AM > DMA. The results are suggestive that in the food-processing industry the simultaneous contact with biogenic amines and harmful detergents like SLS should be minimized. Copyright 2005 S. Karger AG, Basel.

  7. The "Gut Feeling": Breaking Down the Role of Gut Microbiome in Multiple Sclerosis.

    Science.gov (United States)

    Freedman, Samantha N; Shahi, Shailesh K; Mangalam, Ashutosh K

    2018-01-01

    Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system with unknown etiology. Recently, the gut microbiota has emerged as a potential factor in the development of MS, with a number of studies having shown that patients with MS exhibit gut dysbiosis. The gut microbiota helps the host remain healthy by regulating various functions, including food metabolism, energy homeostasis, maintenance of the intestinal barrier, inhibition of colonization by pathogenic organisms, and shaping of both mucosal and systemic immune responses. Alteration of the gut microbiota, and subsequent changes in its metabolic network that perturb this homeostasis, may lead to intestinal and systemic disorders such as MS. Here we discuss the findings of recent MS microbiome studies and potential mechanisms through which gut microbiota can predispose to, or protect against, MS. These findings highlight the need of an improved understanding of the interactions between the microbiota and host for developing therapies based on gut commensals with which to treat MS.

  8. Recent developments in the pathophysiology of irritable bowel syndrome.

    Science.gov (United States)

    El-Salhy, Magdy

    2015-07-07

    Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, the pathophysiology of which is not completely known, although it has been shown that genetic/social learning factors, diet, intestinal microbiota, intestinal low-grade inflammation, and abnormal gastrointestinal endocrine cells play a major role. Studies of familial aggregation and on twins have confirmed the heritability of IBS. However, the proposed IBS risk genes are thus far nonvalidated hits rather than true predisposing factors. There is no convincing evidence that IBS patients suffer from food allergy/intolerance, with the effect exerted by diet seemingly caused by intake of poorly absorbed carbohydrates and fiber. Obesity is a possible comorbidity of IBS. Differences in the microbiota between IBS patients and healthy controls have been reported, but the association between IBS symptoms and specific bacterial species is uncertain. Low-grade inflammation appears to play a role in the pathophysiology of a major subset of IBS, namely postinfectious IBS. The density of intestinal endocrine cells is reduced in patients with IBS, possibly as a result of genetic factors, diet, intestinal microbiota, and low-grade inflammation interfering with the regulatory signals controlling the intestinal stem-cell clonogenic and differentiation activities. Furthermore, there is speculation that this decreased number of endocrine cells is responsible for the visceral hypersensitivity, disturbed gastrointestinal motility, and abnormal gut secretion seen in IBS patients.

  9. Gut microbiome and bone.

    Science.gov (United States)

    Ibáñez, Lidia; Rouleau, Matthieu; Wakkach, Abdelilah; Blin-Wakkach, Claudine

    2018-04-11

    The gut microbiome is now viewed as a tissue that interacts bidirectionally with the gastrointestinal, immune, endocrine and nervous systems, affecting the cellular responses in numerous organs. Evidence is accumulating of gut microbiome involvement in a growing number of pathophysiological processes, many of which are linked to inflammatory responses. More specifically, data acquired over the last decade point to effects of the gut microbiome on bone mass regulation and on the development of bone diseases (such as osteoporosis) and of inflammatory joint diseases characterized by bone loss. Mice lacking a gut microbiome have bone mass alteration that can be reversed by gut recolonization. Changes in the gut microbiome composition have been reported in mice with estrogen-deficiency osteoporosis and have also been found in a few studies in humans. Probiotic therapy decreases bone loss in estrogen-deficient animals. The effect of the gut microbiome on bone tissue involves complex mechanisms including modulation of CD4 + T cell activation, control of osteoclastogenic cytokine production and modifications in hormone levels. This complexity may contribute to explain the discrepancies observed betwwen some studies whose results vary depending on the age, gender, genetic background and treatment duration. Further elucidation of the mechanisms involved is needed. However, the available data hold promise that gut microbiome manipulation may prove of interest in the management of bone diseases. Copyright © 2018 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  10. Radiation and Gut

    International Nuclear Information System (INIS)

    Potten, C.S.; Hendry, J.H.

    1995-08-01

    Texts on gut with reference to radiation (or other cytotoxic and carcinogenic agents) consist of primary research papers, review articles, or books which are now very out-of-date. With this in mind, the present book was conceived. Here, with chapters by experts in the field, we cover the basic structure and cell replacement process in the gut, the physical situation relevant for gut radiation exposure and a description of some of the techniques used to study radiation effects, in particular the clonal regeneration assay that assesses stem cell functional capacity. Chapters comprehensively cover the effects of radiation in experimental animal model systems and clinical experiences. The effects of radiation on the supportive tissue of the gut is also reviewed. The special radiation situation involving ingested radionuclides is reviewed and the most important late response-carcinogenesis-within the gut is considered. This book follows a volume on 'Radiation and Skin' (1985) and another on 'Radiation and Bone Marrow' is in preparation. The present volume is intended to cover the anatomy and renewal characteristics of the gut, and its response in terms of carcinogenicity and tissue injury in mammalian species including in particular man. The book is expected to be useful to students and teachers in these topics, as well as clinical oncologists (radiotherapists) and medical oncologists, and industrial health personnel. 70 figs., 20 tabs., 869 refs

  11. Comparative gut physiology symposium: The microbe-gut-brain axis

    Science.gov (United States)

    The Comparative Gut Physiology Symposium titled “The Microbe-Gut-Brain Axis” was held at the Joint Annual Meeting of the American Society of Animal Science and the American Dairy Science Association on Thursday, July 21, 2016, in Salt Lake City Utah. The goal of the symposium was to present basic r...

  12. Effect of Antibiotics on Gut Microbiota, Gut Hormones and Glucose Metabolism

    DEFF Research Database (Denmark)

    Mikkelsen, Kristian H; Frost, Morten; Bahl, Martin Iain

    2015-01-01

    The gut microbiota has been designated as an active regulator of glucose metabolism and metabolic phenotype in a number of animal and human observational studies. We evaluated the effect of removing as many bacteria as possible by antibiotics on postprandial physiology in healthy humans. Meal tests...... tolerance, insulin secretion or plasma lipid concentrations were found. Apart from an acute and reversible increase in peptide YY secretion, no changes were observed in postprandial gut hormone release. As evaluated by selective cultivation of gut bacteria, a broad-spectrum 4-day antibiotics course...... with vancomycin, gentamycin and meropenem induced shifts in gut microbiota composition that had no clinically relevant short or long-term effects on metabolic variables in healthy glucose-tolerant males. clinicaltrials.gov NCT01633762....

  13. The Immune System in Irritable Bowel Syndrome

    Science.gov (United States)

    Cremon, Cesare; Carini, Giovanni; Bellacosa, Lara; Zecchi, Lisa; De Giorgio, Roberto; Corinaldesi, Roberto; Stanghellini, Vincenzo

    2011-01-01

    The potential relevance of systemic and gastrointestinal immune activation in the pathophysiology and symptom generation in the irritable bowel syndrome (IBS) is supported by a number of observations. Infectious gastroenteritis is the strongest risk factor for the development of IBS and increased rates of IBS-like symptoms have been detected in patients with inflammatory bowel disease in remission or in celiac disease patients on a gluten free diet. The number of T cells and mast cells in the small and large intestine of patients with IBS is increased in a large proportion of patients with IBS over healthy controls. Mediators released by immune cells and likely from other non-immune competent cells impact on the function of enteric and sensory afferent nerves as well as on epithelial tight junctions controlling mucosal barrier of recipient animals, isolated human gut tissues or cell culture systems. Antibodies against microbiota antigens (bacterial flagellin), and increased levels of cytokines have been detected systemically in the peripheral blood advocating the existence of abnormal host-microbial interactions and systemic immune responses. Nonetheless, there is wide overlap of data obtained in healthy controls; in addition, the subsets of patients showing immune activation have yet to be clearly identified. Gender, age, geographic differences, genetic predisposition, diet and differences in the intestinal microbiota likely play a role and further research has to be done to clarify their relevance as potential mechanisms in the described immune system dysregulation. Immune activation has stimulated interest for the potential identification of biomarkers useful for clinical and research purposes and the development of novel therapeutic approaches. PMID:22148103

  14. Studies on aerosols. XI. Influence of particulate matter on the eye irritation produced by volatile irritants and importance of particle size in connection with atmospheric pollution

    Energy Technology Data Exchange (ETDEWEB)

    Dautrebande, L; Shaver, J; Capps, R

    1951-01-01

    This is a review of smog irritation prevented by water filters which remove > 2-..mu..m particles. Formaldehyde, HNO/sub 3/, H/sub 2/SO/sub 4/ vapors combined plus used oil produced stronger irritation than vapors alone. Vapors produced irritation essentially only at concentrations above 4.2 x 10/sup -3/ mg/liter air of each constituent. Three trained human volunteers were exposed to various aerosols via goggles. Blinking and lacrimation were observed. Reaction varied largely between the 3 and between different exposure periods. NaCl, Si dust, and used oil in combination required a much higher concentration to produce eye irritation than with vapors present. NaCl and Si combined did not irritate; used oil did. Photomicrographs showed small (approx. 0.05 ..mu..m), long-chained (1 to 7 ..mu..m), and aggregated (1 to 10 ..mu..m) particles.

  15. Going up in Smoke? A Review of nAChRs-based Treatment Strategies for Improving Cognition in Schizophrenia

    Science.gov (United States)

    Boggs, Douglas L.; Carlson, Jon; Cortes-Briones, Jose; Krystal, John H.; D’Souza, D. Cyril

    2015-01-01

    Cognitive impairment is known to be a core deficit in schizophrenia. Existing treatments for schizophrenia have limited efficacy against cognitive impairment. The ubiquitous use of nicotine in this population is thought to reflect an attempt by patients to self-medicate certain symptoms associated with the illness. Concurrently there is evidence that nicotinic receptors that have lower affinity for nicotine are more important in cognition. Therefore, a number of medications that target nicotinic acetylcholine receptors (nAChRs) have been tested or are in development. In this article we summarize the clinical evidence of nAChRs dysfunction in schizophrenia and review clinical studies testing either nicotine or nicotinic medications for the treatment of cognitive impairment in schizophrenia. Some evidence suggests beneficial effects of nAChRs based treatments for the attentional deficits associated with schizophrenia. Standardized cognitive test batteries have failed to capture consistent improvements from drugs acting at nAChRs. However, more proximal measures of brain function, such as ERPs relevant to information processing impairments in schizophrenia, have shown some benefit. Further work is necessary to conclude that nAChRs based treatments are of clinical utility in the treatment of cognitive deficits of schizophrenia. PMID:24345265

  16. In search of allosteric modulators of a7-nAChR by solvent density guided virtual screening.

    Science.gov (United States)

    Dey, Raja; Chen, Lin

    2011-04-01

    Nicotinic acetylcholine receptors (nAChR) are pentameric ligand gated ion channels whose activity can be modulated by endogenous neurotransmitters as well as by synthetic ligands that bind the same or distinct sites from the natural ligand. The subtype of α7 nAChR has been considered as a potenial therapeutic target for Alzheimer's disease, schizophrenia and other neurological and psychiatric disorders. Here we have developed a homology model of α7 nAChR based on two high resolution crystal structures with Brookhaven Protein Data Bank (PDB) codes 2QC1 and 2WN9 for threading on one monomer and then for building a pentamer, respectively. A number of small molecule binding sites are identified using Pocket Finder (J. An, M. Tortov, and R. Abagyan, Molecular & Cellular Proteomics, 4.6, 752-761 (2005)) of Internal Coordinate Mechanics (ICM). Remarkably, these computer-identified sites match perfectly with ordered solvent densities found in the high-resolution crystal structure of α1 nAChR, suggesting that the surface cavities in the α7 nAChR model are likely binding sites of small molecules. A high throughput virtual screening by flexible ligand docking of 5008 small molecule compounds was performed at three potential allosteric modulator (AM) binding sites of α7 nAChR using Molsoft ICM software (R. Abagyan, M. Tortov and D. Kuznetsov, J Comput Chem 15, 488-506, (1994)). Some experimentally verified allosteric modulators of α7 like CCMI comp-6, LY 7082101, 5-HI, TQS, PNU-120596, genistein, and NS-1738 ranked among top 100 compounds, while the rest of the compounds in the list could guide further search for new allosteric modulators.

  17. Nicotine-Induced Effects on Nicotinic Acetylcholine Receptors (nAChRs), Ca2+ and Brain-Derived Neurotrophic Factor (BDNF) in STC-1 Cells.

    Science.gov (United States)

    Qian, Jie; Mummalaneni, Shobha K; Alkahtani, Reem M; Mahavadi, Sunila; Murthy, Karnam S; Grider, John R; Lyall, Vijay

    2016-01-01

    In addition to the T2R bitter taste receptors, neuronal nicotinic acetylcholine receptors (nAChRs) have recently been shown to be involved in the bitter taste transduction of nicotine, acetylcholine and ethanol. However, at present it is not clear if nAChRs are expressed in enteroendocrine cells other than beta cells of the pancreas and enterochromaffin cells, and if they play a role in the synthesis and release of neurohumoral peptides. Accordingly, we investigated the expression and functional role of nAChRs in enteroendocrine STC-1 cells. Our studies using RT-PCR, qRT-PCR, immunohistochemical and Western blotting techniques demonstrate that STC-1 cells express several α and β nAChR subunits. Exposing STC-1 cells to nicotine acutely (24h) or chronically (4 days) induced a differential increase in the expression of nAChR subunit mRNA and protein in a dose- and time-dependent fashion. Mecamylamine, a non-selective antagonist of nAChRs, inhibited the nicotine-induced increase in mRNA expression of nAChRs. Exposing STC-1 cells to nicotine increased intracellular Ca2+ in a dose-dependent manner that was inhibited in the presence of mecamylamine or dihydro-β-erythroidine, a α4β2 nAChR antagonist. Brain-derived neurotrophic factor (BDNF) mRNA and protein were detected in STC-1 cells using RT-PCR, specific BDNF antibody, and enzyme-linked immunosorbent assay. Acute nicotine exposure (30 min) decreased the cellular content of BDNF in STC-1 cells. The nicotine-induced decrease in BDNF was inhibited in the presence of mecamylamine. We also detected α3 and β4 mRNA in intestinal mucosal cells and α3 protein expression in intestinal enteroendocrine cells. We conclude that STC-1 cells and intestinal enteroendocrine cells express nAChRs. In STC-1 cells nAChR expression is modulated by exposure to nicotine in a dose- and time-dependent manner. Nicotine interacts with nAChRs and inhibits BDNF expression in STC-1 cells.

  18. Gut microbiota and metabolic syndrome.

    Science.gov (United States)

    Festi, Davide; Schiumerini, Ramona; Eusebi, Leonardo Henry; Marasco, Giovanni; Taddia, Martina; Colecchia, Antonio

    2014-11-21

    Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenced by diet. This complex intestinal "superorganism" seems to affect host metabolic balance modulating energy absorption, gut motility, appetite, glucose and lipid metabolism, as well as hepatic fatty storage. An impairment of the fine balance between gut microbes and host's immune system could culminate in the intestinal translocation of bacterial fragments and the development of "metabolic endotoxemia", leading to systemic inflammation and insulin resistance. Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition, that seem to affect the success, or the inefficacy, of treatment strategies. Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss. However, further evidence is needed to better understand their clinical impact and therapeutic use.

  19. Do interactions between stress and immune responses lead to symptom exacerbations in irritable bowel syndrome?

    Science.gov (United States)

    O'Malley, Dervla; Quigley, Eamonn M M; Dinan, Timothy G; Cryan, John F

    2011-10-01

    Irritable bowel syndrome (IBS) is a common, debilitating gastrointestinal (GI) disorder, with a worldwide prevalence of between 10% and 20%. This functional gut disorder is characterized by episodic exacerbations of a cluster of symptoms including abdominal pain, bloating and altered bowel habit, including diarrhea and/or constipation. Risk factors for the development of IBS include a family history of the disorder, childhood trauma and prior gastrointestinal infection. It is generally accepted that brain-gut axis dysfunction is fundamental to the development of IBS; however the underlying pathophysiological mechanisms remain elusive. Additional considerations in comprehending the chronic relapsing pattern that typifies IBS symptoms are the effects of both psychosocial and infection-related stresses. Indeed, co-morbidity with mood disorders such as depression and anxiety is common in IBS. Accumulating evidence points to a role for a maladaptive stress response in the initiation, persistence and severity of IBS-associated symptom flare-ups. Moreover, mechanistically, the stress-induced secretion of corticotropin-releasing factor (CRF) is known to mediate changes in GI function. Activation of the immune system also appears to be important in the generation of IBS symptoms and increasing evidence now implicates low-grade inflammation or immune activation in IBS pathophysiology. There is a growing body of research focused on understanding at a molecular, cellular and in vivo level, the relationship between the dysregulated stress response and immune system alterations (either individually or in combination) in the etiology of IBS and to the occurrence of symptoms. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Systematic review: Complementary and alternative medicine in the irritable bowel syndrome.

    LENUS (Irish Health Repository)

    Hussain, Z

    2012-02-03

    BACKGROUND: Complementary and alternative medical therapies and practices are widely employed in the treatment of the irritable bowel syndrome. AIM: To review the usage of complementary and alternative medicine in the irritable bowel syndrome, and to assess critically the basis and evidence for its use. METHODS: A systematic review of complementary and alternative medical therapies and practices in the irritable bowel syndrome was performed based on literature obtained through a Medline search. RESULTS: A wide variety of complementary and alternative medical practices and therapies are commonly employed by irritable bowel syndrome patients both in conjunction with and in lieu of conventional therapies. As many of these therapies have not been subjected to controlled clinical trials, some, at least, of their efficacy may reflect the high-placebo response rate that is characteristic of irritable bowel syndrome. Of those that have been subjected to clinical trials most have involved small poor quality studies. There is, however, evidence to support efficacy for hypnotherapy, some forms of herbal therapy and certain probiotics in irritable bowel syndrome. CONCLUSIONS: Doctors caring for irritable bowel syndrome patients need to recognize the near ubiquity of complementary and alternative medical use among this population and the basis for its use. All complementary and alternative medicine is not the same and some, such as hypnotherapy, forms of herbal therapy, specific diets and probiotics, may well have efficacy in irritable bowel syndrome. Above all, we need more science and more controlled studies; the absence of truly randomized placebo-controlled trials for many of these therapies has limited meaningful progress in this area.

  1. Neural Correlates of Irritability in Disruptive Mood Dysregulation and Bipolar Disorders.

    Science.gov (United States)

    Wiggins, Jillian Lee; Brotman, Melissa A; Adleman, Nancy E; Kim, Pilyoung; Oakes, Allison H; Reynolds, Richard C; Chen, Gang; Pine, Daniel S; Leibenluft, Ellen

    2016-07-01

    Bipolar disorder and disruptive mood dysregulation disorder (DMDD) are clinically and pathophysiologically distinct, yet irritability can be a clinical feature of both illnesses. The authors examine whether the neural mechanisms mediating irritability differ between bipolar disorder and DMDD, using a face emotion labeling paradigm because such labeling is deficient in both patient groups. The authors hypothesized that during face emotion labeling, irritability would be associated with dysfunctional activation in the amygdala and other temporal and prefrontal regions in both disorders, but that the nature of these associations would differ between DMDD and bipolar disorder. During functional MRI acquisition, 71 youths (25 with DMDD, 24 with bipolar disorder, and 22 healthy youths) performed a labeling task with happy, fearful, and angry faces of varying emotional intensity. Participants with DMDD and bipolar disorder showed similar levels of irritability and did not differ from each other or from healthy youths in face emotion labeling accuracy. Irritability correlated with amygdala activity across all intensities for all emotions in the DMDD group; such correlation was present in the bipolar disorder group only for fearful faces. In the ventral visual stream, associations between neural activity and irritability were found more consistently in the DMDD group than in the bipolar disorder group, especially in response to ambiguous angry faces. These results suggest diagnostic specificity in the neural correlates of irritability, a symptom of both DMDD and bipolar disorder. Such evidence of distinct neural correlates suggests the need to evaluate different approaches to treating irritability in the two disorders.

  2. Inhibitory effects of psychotropic drugs on the acetylcholine receptor-operated potassium current (IK.ACh) in guinea-pig atrial myocytes.

    Science.gov (United States)

    Okada, Muneyoshi; Watanabe, Shinya; Matada, Takashi; Asao, Yoko; Hamatani, Ramu; Yamawaki, Hideyuki; Hara, Yukio

    2013-01-01

    Influences of psychotropic drugs, six antipsychotics and three antidepressants, on acetylcholine receptor-operated potassium current (IK.ACh) were examined by a whole-cell patch clamp method in freshly isolated guinea-pig atrial myocyte. IK.ACh was induced by a superfusion of carbachol (CCh) or by an intracellular application of guanosine 5'-[thio] triphosphate (GTPγS). To elucidate mechanism for anticholinergic action, IC50 ratio, the ratio of IC50 for GTPγS-activated IK.ACh to CCh-induced IK.ACh, was calculated. Antipsychotics and antidepressants inhibited CCh-induced IK.ACh in a concentration-dependent manner. The IC50 values were as follows; chlorpromazine 0.53 μM, clozapine 0.06 μM, fluphenazine 2.69 μM, haloperidol 2.66 μM, sulpiride 42.3 μM, thioridazine 0.07 μM, amitriptyline 0.03 μM, imipramine 0.22 μM and maprotiline 1.81 μM. The drugs, except for sulpiride, inhibited GTPγS-activated IK.ACh with following IC50 values; chlorpromazine 1.71 μM, clozapine 14.9 μM, fluphenazine 3.55 μM, haloperidol 2.73 μM, thioridazine 1.90 μM, amitriptyline 7.55 μM, imipramine 7.09 μM and maprotiline 5.93 μM. The IC50 ratio for fluphenazine and haloperidol was close to unity. The IC50 ratio for chlorpromazine, clozapine, thioridazine, amitriptyline, imipramine and maprotiline was much higher than unity. The present findings suggest that the psychotropics studied suppress IK.ACh. Chlorpromazine, clozapine, thioridazine, amitriptyline, imipramine, maprotiline and sulpiride are preferentially acting on muscarinic receptor. Fluphenazine and haloperidol may act on G protein and/or potassium channel.

  3. Acute irritant reaction to an antiseptic bath emollient

    OpenAIRE

    Saw, N; Hindmarsh, J

    2005-01-01

    Antiseptic bath emollients are commonly prescribed for treatment of eczema and are generally safe for frequent application. Although acute irritant reactions are uncommon it is nevertheless recognised and could have significant morbidity. This case describes a young male patient who developed an acute irritant reaction localised to the external genitalia, mimicking Fournier's gangrene, after overnight application of Oilatum Plus antiseptic bath emollients.

  4. Deposition of a-C:H films on a nanotrench pattern by bipolar PBII and D

    International Nuclear Information System (INIS)

    Hirata, Yuki; Nakahara, Yuya; Nagato, Keisuke; Choi, Junho

    2016-01-01

    In this study, hydrogenated amorphous carbon (a-C:H) films were deposited on a nanotrench pattern (300 nm pitch, aspect ratio: 2.0) by bipolar-type plasma based ion implantation and deposition technique (bipolar PBII and D), and the effects of bipolar pulse on the film properties were investigated. Moreover, the behaviour of ions and radicals surrounding the nanotrench was analyzed to clarify the coating mechanism and properties of the a-C:H films on the nanotrench. Further, thermal nanoimprint lithography was carried out using the nanotrench pattern coated with a-C:H films as the mold, and the mold release properties were evaluated. All nanotrench surfaces were successfully coated with the a-C:H films, but the film thickness on the top, sidewall, and bottom surfaces of the trench were not uniform. The surface roughness of the a-C:H films was found to decrease at a higher positive voltage; this happens due to the higher electron temperature around the nanotrench because of the surface migration of plasma particles arrived on the trench. The effects of the negative voltage on the behaviour of ions and radicals near the sidewall of the nanotrench are quite similar to those near the microtrench reported previously (Park et al 2014 J. Phys. D: Appl. Phys . 47 335306). However, the positive pulse voltage was also found to affect the behaviour of ions and radicals near the sidewall surface. The incident angles of ions on the sidewall surface increased with the positive pulse voltage because the energy of incoming ions on the trench decreases with increasing positive voltage. Moreover, the incident ion flux on the sidewall is affected by the positive voltage history. Further, the radical flux decreases with increasing positive voltage. It can be concluded that a higher positive voltage at a lower negative voltage condition is good to obtain better film properties and higher film thickness on the sidewall surface. Pattern transfer properties for the nanoimprint formed by

  5. Cumulative irritation potential of topical retinoid formulations.

    Science.gov (United States)

    Leyden, James J; Grossman, Rachel; Nighland, Marge

    2008-08-01

    Localized irritation can limit treatment success with topical retinoids such as tretinoin and adapalene. The factors that influence irritant reactions have been shown to include individual skin sensitivity, the particular retinoid and concentration used, and the vehicle formulation. To compare the cutaneous tolerability of tretinoin 0.04% microsphere gel (TMG) with that of adapalene 0.3% gel and a standard tretinoin 0.025% cream. The results of 2 randomized, investigator-blinded studies of 2 to 3 weeks' duration, which utilized a split-face method to compare cumulative irritation scores induced by topical retinoids in subjects with healthy skin, were combined. Study 1 compared TMG 0.04% with adapalene 0.3% gel over 2 weeks, while study 2 compared TMG 0.04% with tretinoin 0.025% cream over 3 weeks. In study 1, TMG 0.04% was associated with significantly lower cumulative scores for erythema, dryness, and burning/stinging than adapalene 0.3% gel. However, in study 2, there were no significant differences in cumulative irritation scores between TMG 0.04% and tretinoin 0.025% cream. Measurements of erythema by a chromameter showed no significant differences between the test formulations in either study. Cutaneous tolerance of TMG 0.04% on the face was superior to that of adapalene 0.3% gel and similar to that of a standard tretinoin cream containing a lower concentration of the drug (0.025%).

  6. Understanding the gut microbiome of dairy calves: Opportunities to improve early-life gut health.

    Science.gov (United States)

    Malmuthuge, Nilusha; Guan, Le Luo

    2017-07-01

    Early gut microbiota plays a vital role in the long-term health of the host. However, understanding of these microbiota is very limited in livestock species, especially in dairy calves. Neonatal calves are highly susceptible to enteric infections, one of the major causes of calf death, so approaches to improving gut health and overall calf health are needed. An increasing number of studies are exploring the microbial composition of the gut, the mucosal immune system, and early dietary interventions to improve the health of dairy calves, revealing possibilities for effectively reducing the susceptibility of calves to enteric infections while promoting growth. Still, comprehensive understanding of the effect of dietary interventions on gut microbiota-one of the key aspects of gut health-is lacking. Such knowledge may provide in-depth understanding of the mechanisms behind functional changes in response to dietary interventions. Understanding of host-microbial interactions with dietary interventions and the role of the gut microbiota during pathogenesis at the site of infection in early life is vital for designing effective tools and techniques to improve calf gut health. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  7. [Gut microbiome and psyche: paradigm shift in the concept of brain-gut axis].

    Science.gov (United States)

    Konturek, Peter C; Zopf, Yurdagül

    2016-05-25

    The concept of the brain-gut axis describes the communication between the central and enteric nervous system. The exchange of information takes place in both directions. The great advances in molecular medicine in recent years led to the discovery of an enormous number of microorganisms in the intestine (gut microbiome), which greatly affect the function of the brain-gut axis. Overview Numerous studies indicate that the dysfunction of the brain-gut axis could lead to both inflammatory and functional diseases of the gastrointestinal tract. Moreover, it was shown that a faulty composition of the gut microbiota in childhood influences the maturation of the central nervous system and thus may favor the development of mental disorders such as autism, depression, or other. An exact causal relationship between psyche and microbiome must be clarified by further studies in order to find new therapeutic options.

  8. Preparation of irritant polymer samples for an in vitro round robin study.

    NARCIS (Netherlands)

    Coleman, Kelly P; Grailer, Thomas P; McNamara, Lori R; Rollins, Beau L; Christiano, Nicholas J; Kandárová, Helena; De Jong, Wim H

    2018-01-01

    A round robin study using reconstructed human epidermis (RhE) tissues was conducted to test medical device polymer extracts for skin irritation potential. Test samples were four irritant and three non-irritant medical device polymers. Five of these polymer samples were developed and two were

  9. Effect of Antibiotics on Gut Microbiota, Gut Hormones and Glucose Metabolism

    DEFF Research Database (Denmark)

    Mikkelsen, Kristian H; Frost, Morten; Bahl, Martin Iain

    2015-01-01

    The gut microbiota has been designated as an active regulator of glucose metabolism and metabolic phenotype in a number of animal and human observational studies. We evaluated the effect of removing as many bacteria as possible by antibiotics on postprandial physiology in healthy humans. Meal tests...... with measurements of postprandial glucose tolerance and postprandial release of insulin and gut hormones were performed before, immediately after and 6 weeks after a 4-day, broad-spectrum, per oral antibiotic cocktail (vancomycin 500 mg, gentamycin 40 mg and meropenem 500 mg once-daily) in a group of 12 lean...... and glucose tolerant males. Faecal samples were collected for culture-based assessment of changes in gut microbiota composition. Acute and dramatic reductions in the abundance of a representative set of gut bacteria was seen immediately following the antibiotic course, but no changes in postprandial glucose...

  10. Vitrigel-eye irritancy test method using HCE-T cells.

    Science.gov (United States)

    Yamaguchi, Hiroyuki; Kojima, Hajime; Takezawa, Toshiaki

    2013-10-01

    We previously reported that the time-dependent relative changes of transepithelial electrical resistance (TEER) after exposing four different chemicals to a human corneal epithelium (HCE) model were well correlated to the potential of ocular irritancy. Meanwhile, we recently developed a collagen vitrigel membrane (CVM) chamber possessing a scaffold composed of high-density collagen fibrils equivalent to connective tissues in vivo as a three-dimensional culture tool. The CVM chamber is useful for biomedical assays and immunohistology using cryosections that are inappropriate to be performed using the conventional Millicell chamber with a polyethylene terephthalate membrane. In this study, we aimed to develop a new eye irritancy test (EIT) method called "Vitrigel-EIT method" that can facilitate to briefly and accurately estimate the widespread irritancy of test chemicals by applying the TEER assay system to a HCE model fabricated in the CVM chamber. HCE-T cells (a HCE-derived cell strain) were cultured in the CVM chamber for 6 days, and consequently, the Vitrigel-HCE model possessing the following characteristics of HCE in vivo was formed: six cell layers with specific protein expressions and their barrier function. Time-dependent profiles of TEER values after exposing 30 test chemicals to the HCE model were converted into the scores of three indexes (time lag, intensity, and plateau level), and each chemical was successfully classified into irritant or nonirritant category by utilizing the criteria for the indexes, resulting in the excellent correlation with Globally Harmonized System of Classification and Labelling of Chemicals (GHS) classification (sensitivity: 100%, specificity: 75%, accuracy: 90%). These data suggest that the widespread eye irritancy of chemicals can be predicted without false negatives by the Vitrigel-EIT method. Interestingly, the disruption of tight junctions was immunohistologically observed after exposing not only irritants but also three

  11. Gut-Brain Axis and Behavior.

    Science.gov (United States)

    Martin, Clair R; Mayer, Emeran A

    2017-01-01

    In the last 5 years, interest in the interactions among the gut microbiome, brain, and behavior has exploded. Preclinical evidence supports a role of the gut microbiome in behavioral responses associated with pain, emotion, social interactions, and food intake. Limited, but growing, clinical evidence comes primarily from associations of gut microbial composition and function to behavioral and clinical features and brain structure and function. Converging evidence suggests that the brain and the gut microbiota are in bidirectional communication. Observed dysbiotic states in depression, chronic stress, and autism may reflect altered brain signaling to the gut, while altered gut microbial signaling to the brain may play a role in reinforcing brain alterations. On the other hand, primary dysbiotic states due to Western diets may signal to the brain, altering ingestive behavior. While studies performed in patients with depression and rodent models generated by fecal microbial transfer from such patients suggest causation, evidence for an influence of acute gut microbial alterations on human behavioral and clinical parameters is lacking. Only recently has an open-label microbial transfer therapy in children with autism tentatively validated the gut microbiota as a therapeutic target. The translational potential of preclinical findings remains unclear without further clinical investigation. © 2017 Nestec Ltd., Vevey/S. Karger AG, Basel.

  12. Metagenomic Surveys of Gut Microbiota

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    Rahul Shubhra Mandal

    2015-06-01

    Full Text Available Gut microbiota of higher vertebrates is host-specific. The number and diversity of the organisms residing within the gut ecosystem are defined by physiological and environmental factors, such as host genotype, habitat, and diet. Recently, culture-independent sequencing techniques have added a new dimension to the study of gut microbiota and the challenge to analyze the large volume of sequencing data is increasingly addressed by the development of novel computational tools and methods. Interestingly, gut microbiota maintains a constant relative abundance at operational taxonomic unit (OTU levels and altered bacterial abundance has been associated with complex diseases such as symptomatic atherosclerosis, type 2 diabetes, obesity, and colorectal cancer. Therefore, the study of gut microbial population has emerged as an important field of research in order to ultimately achieve better health. In addition, there is a spontaneous, non-linear, and dynamic interaction among different bacterial species residing in the gut. Thus, predicting the influence of perturbed microbe–microbe interaction network on health can aid in developing novel therapeutics. Here, we summarize the population abundance of gut microbiota and its variation in different clinical states, computational tools available to analyze the pyrosequencing data, and gut microbe–microbe interaction networks.

  13. Carbohydrates and the human gut microbiota.

    Science.gov (United States)

    Chassard, Christophe; Lacroix, Christophe

    2013-07-01

    Due to its scale and its important role in maintaining health, the gut microbiota can be considered as a 'new organ' inside the human body. Many complex carbohydrates are degraded and fermented by the human gut microbiota in the large intestine to both yield basic energy salvage and impact gut health through produced metabolites. This review will focus on the gut microbes and microbial mechanisms responsible for polysaccharides degradation and fermentation in the large intestine. Gut microbes and bacterial metabolites impact the host at many levels, including modulation of inflammation, and glucose and lipid metabolisms. A complex relationship occurs in the intestine between the human gut microbiota, diet and the host. Research on carbohydrates and gut microbiota composition and functionality is fast developing and will open opportunities for prevention and treatment of obesity, diabetes and other related metabolic disorders through manipulation of the gut ecosystem.

  14. Cognitive-behavioral therapy for patients with irritable bowel syndrome: current insights.

    Science.gov (United States)

    Kinsinger, Sarah W

    2017-01-01

    Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI) condition associated with significant health care utilization and quality-of-life impairment. Latest research indicates that the brain-gut axis plays a key role in the disorder, and the presence of psychological factors and central processing deficits contribute to symptom severity and disability. Psychological therapies as a whole have demonstrated good efficacy in reducing the severity of IBS symptoms. Cognitive-behavioral therapy (CBT) has been tested most rigorously in multiple randomized controlled trials and consistently demonstrates significant and durable effects on IBS symptoms and quality of life. Various protocols for treating IBS have been developed, and most recent advances in the field include exposure-based treatments to target symptom-specific anxiety as well as modified delivery methods, including internet-based treatment models. Despite the well-documented advantages of CBT for IBS, it has been poorly disseminated and few patients have access to this treatment. The primary barrier to dissemination is the limited number of therapists with adequate training in GI psychology to provide this evidence-based intervention. Future developments in the field need to focus on training opportunities to equip more therapists to competently provide CBT for this population. Further efforts to develop telemedicine platforms for delivering this intervention will also improve accessibility for patients.

  15. Irritable mood and the Diagnostic and Statistical Manual of Mental Disorders

    Directory of Open Access Journals (Sweden)

    Safer Daniel J

    2009-10-01

    Full Text Available Abstract Background The terms 'irritable mood' and 'irritability' have been applied to describe and define a variety of different categories in the Diagnostic and Statistical Manual of Mental Disorders (DSM. More precise diagnostic terms and concepts are needed. Methods A concise critical historical review of DSM categories characterized by irritability, anger, and aggression is presented followed by recommendations. Results This analysis describes the broad ranging and imprecise use of the term irritability since the first DSM in 1952. A more age-appropriate and functional realignment of psychiatric categories linked to dysfunctional anger is suggested. Among other recommendations, this realignment would remove irritability as a problematic definer in the present DSM mood categories: expand oppositional defiant disorder to include adults; link the callous unemotional subtype of conduct disorder in adolescents to antisocial personality disorder; move intermittent explosive disorder to an appropriate category: and expand the term 'mood' to apply also to dysfunctional anger and anxiety. Conclusion The non-specific term 'irritability' commonly used in the DSM has had an adverse effect on diagnostic specificity and thereby on treatment. Dysfunctional anger is a major mood disorder which merits a more prominent and better defined representation in psychiatric nomenclature.

  16. Histological distinction between early allergic and irritant patch test reactions

    DEFF Research Database (Denmark)

    Vestergaard, L; Clemmensen, Ole; Sørensen, Flemming Brandt

    1999-01-01

    Comparative light microscopic studies have revealed subtle differences between allergic and irritant reactions in the skin. In the search for specific differences, we focussed on the early inflammatory response. This pilot study was conducted to test the hypothesis that follicular spongiosis can...... differentiate between early allergic and irritant patch test reactions. 8 patients with known contact allergy to either colophony or quarternium-15 participated in the study. In each patient, allergic and irritant patch tests reactions were elicited, and 4-mm punch biopsies were taken after 6 8 h from...... clinically equipotent reactions. Paired sets of slides were assessed blindly by 2 pathologists. 1 patient showing a pityrosporum folliculitis was excluded from the study. All biopsies from allergic patch tests were characterized by follicular spongiosis, while biopsies from irritant patch tests showed...

  17. Acute irritant reaction to an antiseptic bath emollient

    Science.gov (United States)

    Saw, N; Hindmarsh, J

    2005-01-01

    Antiseptic bath emollients are commonly prescribed for treatment of eczema and are generally safe for frequent application. Although acute irritant reactions are uncommon it is nevertheless recognised and could have significant morbidity. This case describes a young male patient who developed an acute irritant reaction localised to the external genitalia, mimicking Fournier's gangrene, after overnight application of Oilatum Plus antiseptic bath emollients. PMID:15701748

  18. CON4EI: EpiOcular™ Eye Irritation Test (EpiOcular™ EIT) for hazard identification and labelling of eye irritating chemicals.

    Science.gov (United States)

    Kandarova, H; Letasiova, S; Adriaens, E; Guest, R; Willoughby, J A; Drzewiecka, A; Gruszka, K; Alépée, Nathalie; Verstraelen, Sandra; Van Rompay, An R

    2018-06-01

    Assessment of the acute eye irritation potential is part of the international regulatory requirements for testing of chemicals. The objective of the CON4EI project was to develop tiered testing strategies for eye irritation assessment. A set of 80 reference chemicals (38 liquids and 42 solids) was tested with eight different methods. Here, the results obtained with the EpiOcular™ Eye Irritation Test (EIT), adopted as OECD TG 492, are shown. The primary aim of this study was to evaluate of the performance of the test method to discriminate between chemicals not requiring classification for serious eye damage/eye irritancy (No Category) and chemicals requiring classification and labelling. In addition, the predictive capacity in terms of in vivo drivers of classification (i.e. corneal opacity, conjunctival redness and persistence at day 21) was investigated. EpiOcular™ EIT achieved a sensitivity of 97%, a specificity of 87% and accuracy of 95% and also confirmed its excellent reproducibility (100%) from the original validation. The assay was applicable to all chemical categories tested in this project and its performance was not limited to the particular driver of the classification. In addition to the existing prediction model for dichotomous categorization, a new prediction model for Cat 1 is suggested. Copyright © 2017. Published by Elsevier Ltd.

  19. Fabrication of a Highly-sensitive Acetylcholine Sensor Based on AChOx Immobilized Smart-chips

    Directory of Open Access Journals (Sweden)

    M. M. RAHMAN

    2011-03-01

    Full Text Available Acetylcholine (ACh sensor based on acetylcholine oxidase (AChOx on EDC activated thioglycolic acid self-assembled monolayer (TGA-SAM using smart-chip has been developed. The simple cyclic voltammetry (CV, at 0.1 V/s technique is performed in total investigation, where 0.5M K3Fe(CN6 is utilized as a standard mediator in phosphate buffer solution (PBS, 0.1M. The ACh sensor exhibited a lower detection limit (DL, 0.1392 ± 0.005 nM, a wide linear dynamic range (LDR, 1.0 nM to 1.0 mM, good linearity (R=0.9951, and higher sensitivity (7.3543 ± 0.2 μAμM-1cm-2, and required small sample volume (70.0 μL as well as good stability and reproducibility. The smart-chip system employed a simple and efficient approach to the immobilization of enzymes onto active sensitive surface, which can enhance sensor performances to a large group of bio-molecules for wide range of biomedical applications in health care fields.

  20. Review of Irritable Bowel Syndrome Treatment

    Directory of Open Access Journals (Sweden)

    M.R Ghadir

    2012-05-01

    Full Text Available

    Background and Objectives: Irritable bowel syndrome is one of the most common functional gastrointestinal disorders striking 10-20% of the world population. Although most patients do not take medical assistance, this disease enforces significant cost on the patient and health systems and has negative effects on quality of life of the individual. After diagnosis ,treatment of this disease is the next step. Many pathways of treatment has been introduced and the efficacy of each other has been established in one way or another. The first step in the path of treatment is education and confidence of patients that might also be the most important step. Fiber diet, probiotic, anti-cholinergic and anti antispasmodics, laxatives, anti-diarrhea, the drugs affecting serotonin receptors, antidepressants and anti-anxiety, the chloride channel activator and non-drug methods such as cognitive-behavior therapy, hypnotherapy, acupuncture and herbal medicine each of which has been tested on irritable bowel syndrome and efficacy of each one has been indicated in one way or another. This paper tried to outline new treatments available in addition to categorization and discussion of various treatments for irritable bowel syndrome.

  1. Functionality and stability data of detergent purified nAChR from Torpedo using lipidic matrixes and macroscopic electrophysiology

    Directory of Open Access Journals (Sweden)

    Luis F. Padilla-Morales

    2016-03-01

    Full Text Available The presented data provides additional information about the assessment of affinity purified nicotinic acetylcholine receptor (nAChR rich membrane solubilized with long chain (16 saturated carbons lysophospholipid with glycerol headgroup (LFG-16. The assessment of stability and functionality of solubilized membrane protein is a critical step prior to further crystallization trails. One of the key factors for this task is the appropriate choice of a detergent that can support nAChR activity and stability comparable to the crude membranes. The stability of the nAChR-LFG-16 complex incorporated into lipid cubic phase (LCP was monitored for a period of 30 days by means of fluorescence recovery after photobleaching (FRAP and the functionality was evaluated after its incorporation into Xenopus oocyte by means of the two electrode voltage clamp technique. Keywords: Detergents, Fluorescence recovery after photobleaching, Lipidic Cubic Phase, nAChR, Planar lipid bilayer, Two-electrode voltage clamp

  2. Confirming a Role for α9nAChRs and SK Potassium Channels in Type II Hair Cells of the Turtle Posterior Crista

    Directory of Open Access Journals (Sweden)

    Xiaorong Xu Parks

    2017-11-01

    Full Text Available In turtle posterior cristae, cholinergic vestibular efferent neurons (VENs synapse on type II hair cells, bouton afferents innervating type II hair cells, and afferent calyces innervating type I hair cells. Electrical stimulation of VENs releases acetylcholine (ACh at these synapses to exert diverse effects on afferent background discharge including rapid inhibition of bouton afferents and excitation of calyx-bearing afferents. Efferent-mediated inhibition is most pronounced in bouton afferents innervating type II hair cells near the torus, but becomes progressively smaller and briefer when moving longitudinally through the crista toward afferents innervating the planum. Sharp-electrode recordings have inferred that efferent-mediated inhibition of bouton afferents requires the sequential activation of alpha9-containing nicotinic ACh receptors (α9*nAChRs and small-conductance, calcium-dependent potassium channels (SK in type II hair cells. Gradations in the strength of efferent-mediated inhibition across the crista likely reflect variations in α9*nAChRs and/or SK activation in type II hair cells from those different regions. However, in turtle cristae, neither inference has been confirmed with direct recordings from type II hair cells. To address these gaps, we performed whole-cell, patch-clamp recordings from type II hair cells within a split-epithelial preparation of the turtle posterior crista. Here, we can easily visualize and record hair cells while maintaining their native location within the neuroepithelium. Consistent with α9*nAChR/SK activation, ACh-sensitive currents in type II hair cells were inward at hyperpolarizing potentials but reversed near −90 mV to produce outward currents that typically peaked around −20 mV. ACh-sensitive currents were largest in torus hair cells but absent from hair cells near the planum. In current clamp recordings under zero-current conditions, ACh robustly hyperpolarized type II hair cells. ACh

  3. Diminution of the gut resistome after a gut microbiota-targeted dietary intervention in obese children.

    Science.gov (United States)

    Wu, Guojun; Zhang, Chenhong; Wang, Jing; Zhang, Feng; Wang, Ruirui; Shen, Jian; Wang, Linghua; Pang, Xiaoyan; Zhang, Xiaojun; Zhao, Liping; Zhang, Menghui

    2016-04-05

    The gut microbiome represents an important reservoir of antibiotic resistance genes (ARGs). Effective methods are urgently needed for managing the gut resistome to fight against the antibiotic resistance threat. In this study, we show that a gut microbiota-targeted dietary intervention, which shifts the dominant fermentation of gut bacteria from protein to carbohydrate, significantly diminished the gut resistome and alleviated metabolic syndrome in obese children. Of the non-redundant metagenomic gene catalog of ~2 × 10(6) microbial genes, 399 ARGs were identified in 131 gene types and conferred resistance to 47 antibiotics. Both the richness and diversity of the gut resistome were significantly reduced after the intervention. A total of 201 of the 399 ARGs were carried in 120 co-abundance gene groups (CAGs) directly binned from the gene catalog across both pre-and post-intervention samples. The intervention significantly reduced several CAGs in Klebsiella, Enterobacter and Escherichia, which were the major hubs for multiple resistance gene types. Thus, dietary intervention may become a potentially effective method for diminishing the gut resistome.

  4. Biallelic mutation of UNC50, encoding a protein involved in AChR trafficking, is responsible for arthrogryposis.

    Science.gov (United States)

    Abiusi, Emanuela; D'Alessandro, Manuela; Dieterich, Klaus; Quevarec, Loic; Turczynski, Sandrina; Valfort, Aurore-Cecile; Mezin, Paulette; Jouk, Pierre Simon; Gut, Marta; Gut, Ivo; Bessereau, Jean Louis; Melki, Judith

    2017-10-15

    Arthrogryposis multiplex congenita (AMC) is a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. Homozygosity mapping of disease loci combined with whole exome sequencing in a consanguineous family presenting with lethal AMC allowed the identification of a homozygous frameshift deletion in UNC50 gene (c.750_751del:p.Cys251Phefs*4) in the index case. To assess the effect of the mutation, an equivalent mutation in the Caenorhabditis elegans orthologous gene was created using CRISPR/Cas9. We demonstrated that unc-50(kr331) modification caused the loss of acetylcholine receptor (AChR) expression in C. elegans muscle. unc-50(kr331) animals were as resistant to the cholinergic agonist levamisole as unc-50 null mutants suggesting that AChRs were no longer expressed in this animal model. This was confirmed by using a knock-in strain in which a red fluorescent protein was inserted into the AChR locus: no signal was detected in unc-50(kr331) background, suggesting that UNC-50, a protein known to be involved in AChR trafficking, was no longer functional. These data indicate that biallelic mutation in the UNC50 gene underlies AMC through a probable loss of AChR expression at the neuromuscular junction which is essential for the cholinergic transmission during human muscle development. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. IRRITABLE MOOD IN ADULT MAJOR DEPRESSIVE DISORDER: RESULTS FROM THE WORLD MENTAL HEALTH SURVEYS

    Science.gov (United States)

    Kovess-Masfety, Viviane; Alonso, Jordi; Angermeyer, Matthias; Bromet, Evelyn; de Girolamo, Giovanni; de Jonge, Peter; Demyttenaere, Koen; Florescu, Silvia E.; Gruber, Michael J.; Gureje, Oye; Hu, Chiyi; Huang, Yueqin; Karam, Elie G.; Jin, Robert; Lépine, Jean-Pierre; Levinson, Daphna; McLaughlin, Katie A.; Medina-Mora, María E.; O’Neill, Siobhan; Ono, Yutaka; Posada-Villa, José A.; Sampson, Nancy A.; Scott, Kate M.; Shahly, Victoria; Stein, Dan J.; Viana, Maria C.; Zarkov, Zahari; Kessler, Ronald C.

    2014-01-01

    Background Although irritability is a core symptom of DSM-IV major depressive disorder (MDD) for youth but not adults, clinical studies find comparable rates of irritability between nonbipolar depressed adults and youth. Including irritability as a core symptom of adult MDD would allow detection of depression-equivalent syndromes with primary irritability hypothesized to be more common among males than females. We carried out a preliminary examination of this issue using cross-national community-based survey data from 21 countries in the World Mental Health (WMH) Surveys (n = 110,729). Methods The assessment of MDD in the WHO Composite International Diagnostic Interview includes one question about persistent irritability. We examined two expansions of the definition of MDD involving this question: (1) cases with dysphoria and/or anhedonia and exactly four of nine Criterion A symptoms plus irritability; and (2) cases with two or more weeks of irritability plus four or more other Criterion A MDD symptoms in the absence of dysphoria or anhedonia. Results Adding irritability as a tenth Criterion A symptom increased lifetime prevalence by 0.4% (from 11.2 to 11.6%). Adding episodes of persistent irritability increased prevalence by an additional 0.2%. Proportional prevalence increases were significantly higher, but nonetheless small, among males compared to females. Rates of severe role impairment were significantly lower among respondents with this irritable depression who did not meet conventional DSM-IV criteria than those with DSM-IV MDD. Conclusion Although limited by the superficial assessment in this single question on irritability, results do not support expanding adult MDD criteria to include irritable mood. PMID:23364997

  6. Irritant potential of some constituents from oleo-gum-resin of Commiphora myrrha.

    Science.gov (United States)

    Saeed, M Asif; Sabir, A W

    2004-01-01

    The irritant potentials of essential oil and seven sesquiterpenoids compounds newly isolated from the oleo-gum-resin of Commiphora myrrha were investigated by open mouse ear assay. The essential oil, curzerenone, furanodiene-6-one and furanoeudesma-1,3-diene showed potent and persistent irritant effects while others possess least irritant potentials.

  7. Are Histrionic Personality Traits Associated with Irritability during Conscious Sedation Endoscopy?

    OpenAIRE

    Lee, Sang Shin; Kim, Hyung Hun; Park, Hyo Jung

    2015-01-01

    Aim. We aimed to evaluate whether histrionic personality traits are associated with irritability during conscious sedation endoscopy (CSE). Materials and Methods. A prospective cross-sectional study was planned. Irritability during CSE was classified into five grades: 0, no response; I, minimal movement; II, moderate movement; III, severe movement; IV, fighting against procedure. Patients in grades III and IV were defined as the irritable group. Participants were required to complete question...

  8. Evaluation of Ocular Irritation and Bioavailability of Voriconazole Loaded Microemulsion.

    Science.gov (United States)

    Kumar, Rakesh; Sinha, Vivek Ranjan

    2017-01-01

    Voriconazole (VCZ), a second-generation antifungal with excellent attributes like, broad-spectrum activity, targeted delivery, and tolerability. VCZ loaded microemulsion could be an effective strategy for efficient ocular delivery of the drug. To perform corneal irritation studies and in vivo delivery of VCZ microemulsion to establish its potential as an efficient ocular delivery system. Ocular irritancy was performed by HETCAM (Hen's Egg Test Chorio Allantoic Membrane) assay, corneal histopathology and Draize test. Ex vivo and in vivo studies were performed to determine permeation efficiency of VCZ microemulsion. The irritation studies suggested the non-irritant nature of the microemulsion. The ex vivo studies performed on excised cornea displayed significant enhancement in drug permeation/penetration from microemulsion in contrast to the drug suspension. Further, the in vivo study confirmed the higher availability of VCZ (from microemulsion) in aqueous humor with minimal nasolacrimal drainage (lower plasma drug content) when compared with the drug suspension. The non-irritant nature and high corneal permeation of VCZ encourages the role of microemulsion as a potential ocular delivery system. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Depression in patients with irritable bowel syndrome in Jos,Nigeria

    Institute of Scientific and Technical Information of China (English)

    Nimzing G Ladep; Taiwo J Obindo; Moses D Audu; Edith N Okeke; Abraham O Malu

    2006-01-01

    AIM: To study the brain-gut interaction and the effect of behavioral or psychiatric conditions on irritable bowel syndrome (IBS) in an African population.METHODS: IBS was diagnosed using the Rome Ⅱ diagnostic criteria. The entry of each patient was confirmed following detailed explanations of the questions. Four hundred and eighteen patients were studied. Subjects satisfying the Rome Ⅱ criteria for IBS were physically examined and stool microscopy was done to identify the presence of "alarm factors". Depression was diagnosed using the symptom-check list adapted from the Research Diagnostic Criteria (DSM-Ⅳ) of the American Psychiatric Association.RESULTS: Seventy-five (56.8%) of the 132 IBS patients were depressed whereas only 54 (20.1%) of the 268 non-IBS patients were depressed. There was a significant relationship between IBS and depression (x2= 54.29,Odds ratio = 5.21, 56.8 ± 8.4 vs 20.1 ± 5.2, P = 0.001).Even though constipation predominant IBS patients were more likely to be depressed, no significant relationship was found between the subtype of IBS and depression (x2= 0.02, OR = 0.95, P = 0.68).CONCLUSION: IBS is significantly associated with major depression but not gender and bowel subtypes of the patients. Patients with IBS need to be evaluated for depression due to the highly significant relationship between the two conditions.

  10. PREVALENCE OF SMALL INTESTINAL BACTERIAL OVERGROWTH IN IRRITABLE BOWEL SYNDROME

    Directory of Open Access Journals (Sweden)

    Premaletha Narayanan

    2017-12-01

    Full Text Available BACKGROUND Irritable Bowel Syndrome (IBS is a common functional disorder and the pathophysiology of IBS is poorly understood. The aim of the study is to assess the prevalence of SIBO in patients with IBS using Lactulose Hydrogen Breath Test (LHBT. Diagnosis of IBS was made according to the Rome III Criteria and Lactulose Hydrogen Breath Test (LHBT was done. MATERIALS AND METHODS The current hypothesis suggests that altered gastrointestinal motility, disturbance of visceral hypersensitivity and infection may contribute to the symptoms. Gut microbiota and intestinal pathogens are likely to influence the pathogenesis of IBS. Small Intestinal Bacterial Overgrowth (SIBO is defined as an abnormally high bacterial count (≥105 colony-forming units/mL in the proximal small intestine. RESULTS Out of the 120 patients, 9 were LHBT positive (7.5% compared to none in controls (p <0.01. IBS patients with LHBT positivity was correlated well with the increased frequency of stools. There was no correlation noted with LHBT positivity and abdominal pain or flatulence or bloating compared to IBS patients who were LHBT negative. CONCLUSION These findings may suggest that patients with chronic diarrhoea including IBS should be tested for SIBO. Our study also showed that LHBT positivity is associated with increased frequency of stools and diarrhoea. If SIBO is found in patients with chronic diarrhoea, specific treatment with antibiotics may benefit them.

  11. Low-FODMAP Diet for Irritable Bowel Syndrome: Is It Ready for Prime Time?

    Science.gov (United States)

    Khan, Muhammad Ali; Nusrat, Salman; Khan, Muhammad Imran; Nawras, Ali; Bielefeldt, Klaus

    2015-05-01

    Irritable bowel syndrome (IBS) is a chronic gastrointestinal disease, which adversely affects the quality of life. Its prevalence has been reported to be around 10-15 % in North America and constitutes the most common cause for gastroenterology referral. Unfortunately, the pathophysiology of IBS is not completely understood. Not surprisingly, the management strategies can leave the patients with inadequate symptom control, making IBS a debilitating gastrointestinal syndrome. Dietary interventions as a treatment strategy for IBS have been recently evaluated. One such intervention includes dietary restriction of fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs). FODMAPs define a group of short-chain carbohydrates that are incompletely absorbed in small intestine and later fermented in the colon. Evidence in the form of randomized controlled trials and observational studies have evaluated the mechanism of action and efficacy of low-FODMAP diet. This dietary intervention has showed promising results in symptom reduction in IBS patients. However, latest trials have also shown that the low-FODMAP diet is associated with marked changes in gut microbiota specifically reduction in microbiota with prebiotic properties. Implications of such changes on gastrointestinal health need to be further evaluated in future trials.

  12. Gut Microbiome and Infant Health: Brain-Gut-Microbiota Axis and Host Genetic Factors.

    Science.gov (United States)

    Cong, Xiaomei; Xu, Wanli; Romisher, Rachael; Poveda, Samantha; Forte, Shaina; Starkweather, Angela; Henderson, Wendy A

    2016-09-01

    The development of the neonatal gut microbiome is influenced by multiple factors, such as delivery mode, feeding, medication use, hospital environment, early life stress, and genetics. The dysbiosis of gut microbiota persists during infancy, especially in high-risk preterm infants who experience lengthy stays in the Neonatal intensive care unit (NICU). Infant microbiome evolutionary trajectory is essentially parallel with the host (infant) neurodevelopmental process and growth. The role of the gut microbiome, the brain-gut signaling system, and its interaction with the host genetics have been shown to be related to both short and long term infant health and bio-behavioral development. The investigation of potential dysbiosis patterns in early childhood is still lacking and few studies have addressed this host-microbiome co-developmental process. Further research spanning a variety of fields of study is needed to focus on the mechanisms of brain-gut-microbiota signaling system and the dynamic host-microbial interaction in the regulation of health, stress and development in human newborns.

  13. Targeting the ecology within: The role of the gut-brain axis and human microbiota in drug addiction.

    Science.gov (United States)

    Skosnik, Patrick D; Cortes-Briones, Jose A

    2016-08-01

    Despite major advances in our understanding of the brain using traditional neuroscience, reliable and efficacious treatments for drug addiction have remained elusive. Hence, the time has come to utilize novel approaches, particularly those drawing upon contemporary advances in fields outside of established neuroscience and psychiatry. Put another way, the time has come for a paradigm shift in the addiction sciences. Apropos, a revolution in the area of human health is underway, which is occurring at the nexus between enteric microbiology and neuroscience. It has become increasingly clear that the human microbiota (the vast ecology of bacteria residing within the human organism), plays an important role in health and disease. This is not surprising, as it has been estimated that bacteria living in the human body (approximately 1kg of mass, roughly equivalent to that of the human brain) outnumber human cells 10 to 1. While advances in the understanding of the role of microbiota in other areas of human health have yielded intriguing results (e.g., Clostridium difficile, irritable bowel syndrome, autism, etc.), to date, no systematic programs of research have examined the role of microbiota in drug addiction. The current hypothesis, therefore, is that gut dysbiosis plays a key role in addictive disorders. In the context of this hypothesis, this paper provides a rationale for future research to target the "gut-brain axis" in addiction. A brief background of the gut-brain axis is provided, along with a series of hypothesis-driven ideas outlining potential treatments for addiction via manipulations of the "ecology within." Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through MyD88.

    Science.gov (United States)

    Larsson, Erik; Tremaroli, Valentina; Lee, Ying Shiuan; Koren, Omry; Nookaew, Intawat; Fricker, Ashwana; Nielsen, Jens; Ley, Ruth E; Bäckhed, Fredrik

    2012-08-01

    The gut microbiota has profound effects on host physiology but local host-microbial interactions in the gut are only poorly characterised and are likely to vary from the sparsely colonised duodenum to the densely colonised colon. Microorganisms are recognised by pattern recognition receptors such as Toll-like receptors, which signal through the adaptor molecule MyD88. To identify host responses induced by gut microbiota along the length of the gut and whether these required MyD88, transcriptional profiles of duodenum, jejunum, ileum and colon were compared from germ-free and conventionally raised wild-type and Myd88-/- mice. The gut microbial ecology was assessed by 454-based pyrosequencing and viruses were analysed by PCR. The gut microbiota modulated the expression of a large set of genes in the small intestine and fewer genes in the colon but surprisingly few microbiota-regulated genes required MyD88 signalling. However, MyD88 was essential for microbiota-induced colonic expression of the antimicrobial genes Reg3β and Reg3γ in the epithelium, and Myd88 deficiency was associated with both a shift in bacterial diversity and a greater proportion of segmented filamentous bacteria in the small intestine. In addition, conventionally raised Myd88-/- mice had increased expression of antiviral genes in the colon, which correlated with norovirus infection in the colonic epithelium. This study provides a detailed description of tissue-specific host transcriptional responses to the normal gut microbiota along the length of the gut and demonstrates that the absence of MyD88 alters gut microbial ecology.

  15. Repeated administration of alpha7 nicotinic acetylcholine receptor (nAChR) agonists, but not positive allosteric modulators, increases alpha7 nAChR levels in the brain

    DEFF Research Database (Denmark)

    Christensen, Ditte Z; Mikkelsen, Jens D; Hansen, Henrik H

    2010-01-01

    The alpha7 nicotinic acetylcholine receptor (nAChR) is an important target for treatment of cognitive deficits in schizophrenia and Alzheimer's disease. However, the receptor desensitizes rapidly in vitro, which has led to concern regarding its applicability as a clinically relevant drug target...

  16. Role of alimentation in irritable bowel syndrome.

    Science.gov (United States)

    Dapoigny, M; Stockbrügger, R W; Azpiroz, F; Collins, S; Coremans, G; Müller-Lissner, S; Oberndorff, A; Pace, F; Smout, A; Vatn, M; Whorwell, P

    2003-01-01

    Different food items are made responsible for irritable bowel syndrome (IBS) symptoms, but the physiopathology of IBS remains unclear. During a meeting in Nice, France, experts of the European Working Team of the IBiS Club discussed selected data regarding the relationships between alimentation, food items (including fibers) and IBS symptoms. Food allergy remains a difficult diagnosis, but medical and general history, presence of general symptoms such as skin rash, and hypersensitivity tests may help in achieving a positive diagnosis. On the other hand, food intolerance is more confusing because of the subjectivity of the relationship between ingestion of certain foods and the appearance of clinical symptoms. Different food items which are commonly implicated in adverse reactions mimicking IBS were found to be stimulants for the gut, suggesting that patients with predominant diarrhea IBS have to be carefully questioned about consumption of different kinds of food (i.e., coffee, alcohol, chewing gum, soft drinks) and not only on lactose ingestion. Gas production is discussed on the basis of retention of intestinal gas as well as on malabsorption of fermentable substrates. The role of a large amount of this kind of substrate reaching the colon is suggested as a potential mechanism of IBS-type symptoms in overeating patients. Regarding the role of fiber in IBS, the expert group concluded that fibers are not inert substances and that they could trigger pain or bloating in some IBS patients. Despite numerous reviews on this subject, it is very difficult to give general dietary advice to IBS patients, but dieteticians may have a positive role in managing such patients. Copyright 2003 S. Karger AG, Basel

  17. Respon Konsumen pada Mobile Advergames: Intrusiveness dan Irritation

    Directory of Open Access Journals (Sweden)

    Sony Kusumasondjaja

    2016-12-01

    Full Text Available Abstract. Increasing adoption of mobile advergames to deliver marketing messages has not been followed by empirical findings to support its effectiveness. This research attempts to examine the effect of mobile advergames intrusiveness on consumer irritation, attitudes, and purchase intention. This investigation on mobile advergame effectiveness was based on the increasing use of mobile media to deliver marketing messages to consumers from different demographic background. Conceptual framework was developed based on Advertising Avoidance Theory. For data collection, self-administered survey was conducted by adopting purposive sampling involving 213 respondents residing in Surabaya who have had experience in playing mobile game as respondents. Results indicate that intrusiveness positively affects consumer irritation. Consumer irritation negatively affects attitude towards the mobile advergames and attitude towards the advertised product. The better the consumer attitude towards the mobile advergames, the more positive the attitude towards the advertised product. Moreover, the more positive the attitude towards the advertised product, the greater the consumer intention to purchase. Interestingly, consumer attitude toward the mobile advergames has insignificant influence on purchase intention. Findings of the study offer significant contribution to marketing practices using mobile advergames as media placement in their advertising strategy. Keywords: intrusiveness, irritation, mobile advergames, attitude, advertising

  18. Immunomodulation of enteric neural function in irritable bowel syndrome.

    Science.gov (United States)

    O'Malley, Dervla

    2015-06-28

    Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder which is characterised by symptoms such as bloating, altered bowel habit and visceral pain. It's generally accepted that miscommunication between the brain and gut underlies the changes in motility, absorpto-secretory function and pain sensitivity associated with IBS. However, partly due to the lack of disease-defining biomarkers, understanding the aetiology of this complex and multifactorial disease remains elusive. Anecdotally, IBS patients have noted that periods of stress can result in symptom flares and many patients exhibit co-morbid stress-related mood disorders such as anxiety and depression. However, in addition to psychosocial stressors, infection-related stress has also been linked with the initiation, persistence and severity of symptom flares. Indeed, prior gastrointestinal infection is one of the strongest predictors of developing IBS. Despite a lack of overt morphological inflammation, the importance of immune factors in the pathophysiology of IBS is gaining acceptance. Subtle changes in the numbers of mucosal immune cell infiltrates and elevated levels of circulating pro-inflammatory cytokines have been reproducibly demonstrated in IBS populations. Moreover, these immune mediators directly affect neural signalling. An exciting new area of research is the role of luminal microbiota in the modulation of neuro-immune signalling, resulting in local changes in gastrointestinal function and alterations in central neural functioning. Progress in this area has begun to unravel some of the complexities of neuroimmune and neuroendocrine interactions and how these molecular exchanges contribute to GI dysfunction.

  19. Gut Homeostasis, Microbial Dysbiosis, and Opioids.

    Science.gov (United States)

    Wang, Fuyuan; Roy, Sabita

    2017-01-01

    Gut homeostasis plays an important role in maintaining animal and human health. The disruption of gut homeostasis has been shown to be associated with multiple diseases. The mutually beneficial relationship between the gut microbiota and the host has been demonstrated to maintain homeostasis of the mucosal immunity and preserve the integrity of the gut epithelial barrier. Currently, rapid progress in the understanding of the host-microbial interaction has redefined toxicological pathology of opioids and their pharmacokinetics. However, it is unclear how opioids modulate the gut microbiome and metabolome. Our study, showing opioid modulation of gut homeostasis in mice, suggests that medical interventions to ameliorate the consequences of drug use/abuse will provide potential therapeutic and diagnostic strategies for opioid-modulated intestinal infections. The study of morphine's modulation of the gut microbiome and metabolome will shed light on the toxicological pathology of opioids and its role in the susceptibility to infectious diseases.

  20. Anti-irritant and anti-inflammatory effects of glycerol and xylitol in sodium lauryl sulphate-induced acute irritation.

    Science.gov (United States)

    Szél, E; Polyánka, H; Szabó, K; Hartmann, P; Degovics, D; Balázs, B; Németh, I B; Korponyai, C; Csányi, E; Kaszaki, J; Dikstein, S; Nagy, K; Kemény, L; Erős, G

    2015-12-01

    Glycerol is known to possess anti-irritant and hydrating properties and previous studies suggested that xylitol may also have similar effects. Our aim was to study whether different concentrations of these polyols restore skin barrier function and soothe inflammation in sodium lauryl sulphate (SLS)-induced acute irritation. The experiments were performed on male SKH-1 hairless mice. The skin of the dorsal region was exposed to SLS (5%) for 3 h alone or together with 5% or 10% of glycerol respectively. Further two groups received xylitol solutions (8.26% and 16.52% respectively) using the same osmolarities, which were equivalent to those of the glycerol treatments. The control group was treated with purified water. Transepidermal water loss (TEWL) and skin hydration were determined. Microcirculatory parameters of inflammation were observed by means of intravital videomicroscopy (IVM). Furthermore, accumulation of neutrophil granulocytes and lymphocytes, the expression of inflammatory cytokines and SLS penetration were assessed, as well. Treatment with the 10% of glycerol and both concentrations of xylitol inhibited the SLS-induced elevation of TEWL and moderated the irritant-induced increase in dermal blood flow and in the number of leucocyte-endothelial interactions. All concentrations of the applied polyols improved hydration and prevented the accumulation of lymphocytes near the treatment site. At the mRNA level, neither glycerol nor xylitol influenced the expression of interleukin-1 alpha. However, expression of interleukin-1 beta was significantly decreased by the 10% glycerol treatment, while expression of tumour necrosis factor-alpha decreased upon the same treatment, as well as in response to xylitol. Higher polyol treatments decreased the SLS penetration to the deeper layers of the stratum corneum. Both of the analysed polyols exert considerable anti-irritant and anti-inflammatory properties, but the effective concentration of xylitol is lower than that of

  1. Molecular restrictions for human eye irritation by chemical vapors

    International Nuclear Information System (INIS)

    Cometto-Muniz, J. Enrique; Cain, William S.; Abraham, Michael H.

    2005-01-01

    Previous research showed a cut-off along homologous volatile organic compounds (VOCs) in their ability to produce acute human mucosal irritation. The present study sought to specify the particular cut-off homolog for sensory eye irritation in an acetate and n-alcohol series. A 1900-ml glass vessel system and a three-alternative forced-choice procedure served to test nonyl, decyl, and dodecyl acetate, and 1-nonanol, 1-decanol, and 1-undecanol. Flowrate to the eye ranged from 2 to 8 L/min and time of exposure from 3 to 24 s. Decyl acetate and 1-undecanol were the shortest homologs that failed to produce eye irritation under all conditions, producing a cut-off effect. Increasing the vapor concentration of decyl acetate and 1-undecanol by 3 and 8 times, respectively, via heating them to 37 deg C made either or both VOCs detectable to only half of the 12 subjects tested, even though the higher vapor concentration was well above a predicted eye irritation threshold. When eye irritation thresholds for homologous acetates and n-alcohols were plotted as a function of the longest unfolded length of the molecule, the values for decyl acetate and 1-undecanol fell within a restricted range of 18 to 19 A. The outcome suggests that the basis for the cut-off is biological, that is, the molecule lacks a key size or structure to trigger transduction, rather than physical, that is, the vapor concentration is too low to precipitate detection

  2. Building a Definition of Irritability From Academic Definitions and Lay Descriptions.

    Science.gov (United States)

    Barata, Paula C; Holtzman, Susan; Cunningham, Shannon; O'Connor, Brian P; Stewart, Donna E

    2016-04-08

    The current work builds a definition of irritability from both academic definitions and lay perspectives. In Study 1, a quantitative content analysis of academic definitions resulted in eight main content categories (i.e., behaviour, emotion or affect, cognition, physiological, qualifiers, irritant, stability or endurance, and other). In Study 2, a community sample of 39 adults participated in qualitative interviews. A deductive thematic analysis resulted in two main themes. The first main theme dealt with how participants positioned irritability in relation to other negative states. The second dealt with how participants constructed irritability as both a loss of control and as an experience that should be controlled. The discussion integrates the findings of both studies and provides a concise, but comprehensive definition.

  3. Deposition and characterisation of multilayer hard coatings. Ti/TiNδ/TiCxNy/(TiC) a-C:H/(Ti) a-C:H

    International Nuclear Information System (INIS)

    Burinprakhon, T.

    2001-02-01

    Multilayer hard coatings containing Ti, TiNδ, TiC x N y , (TiC m ) a-C:H, (TiC n ) a-C:H, and (Ti) a-C:H were deposited on commercially pure titanium substrates by using an asymmetric bipolar pulsed-dc reactive magnetron sputtering of a titanium target, with Ar, Ar+N 2 , Ar+N 2 +CH 4 , and Ar+CH 4 gas mixtures. The microstructures, elemental compositions and bonding states of the interlayers and the coating surfaces were studied by using cross-sectional transmission electron microscopy (XTEM), electron energy loss spectroscopy (EELS), X-ray diffraction (XRD), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). The microstructure development of the multilayer coating was strongly influenced by target poisoning. As a result of the complete poisoning of the titanium target during the deposition of TiNδ and TiC x N y interlayers, the a-C:H interlayers containing graded titanium and nitrogen contents were found to develop successively to the TiC x N y interlayer without the formation of near-stoichiometric TiC. The (TiC m ) a-C:H interlayer consisted of nano-particles of distorted fcc crystal structure embedded in the a-C:H matrix. The (TiC n ) a-C:H and (Ti) a-C:H top layers were found to be a-C:H matrix without nano-particles. In the (Ti) a-C:H top layer there was no measurable amount of Ti observed, regardless of the variation of CH 4 concentration between 37.5 and 60 % flow rate in Ar+-CH4 gas mixture. The top layer (Ti) a-C:H was found to contain approximately 10 atomic % nitrogen, due to N 2 contamination during deposition caused by low conductance of N 2 through the nominally closed valve of the mass flow controller. The change of the CH 4 concentration during deposition of the top layer (Ti) a-C:H, however, showed a strong influence on the hydrogen content. The comparison of the fluorescence background of the Raman spectra revealed that hydrogen-less (Ti) a-C:H was deposited at a CH 4 concentration of less than 50 % flow rate in Ar. The hardness

  4. Cytological changes and conjunctival hyperemia in relation to sensory eye irritation

    DEFF Research Database (Denmark)

    Hempel-Jørgensen, Anne; Kjærgaard, Søren K.; Mølhave, Lars

    1998-01-01

    irritation and possible physiological/pathological changes in the mucosal membranes in relation to studies of indoor air. Two studies (study 1 and study 2) were conducted to investigate changes in conjunctival hyperemia and conjunctival fluid cytology for subjects exposed to volatile organic compounds (VOCs...... and conjunctival fluid was sampled before and after exposure. Moreover, the perceived irritation intensities were registered continuously during exposure. Overall, perceived irritation intensity and conjunctival hyperemia increased with increasing exposure concentrations, whereas cytological changes...

  5. The relationship of reports of aches and joint pains to the menopausal transition: a longitudinal study.

    Science.gov (United States)

    Szoeke, C E; Cicuttini, F M; Guthrie, J R; Dennerstein, L

    2008-02-01

    OBJECTIVES Part I: To determine factors associated with reported joint symptoms across the menopausal transition. Part II: To investigate the relationship between symptom reporting and radiological arthritis in postmenopausal women. DESIGN Part I: The Melbourne Women's Mid-life Health Project, commenced in 1991, is a population-based prospective study of 438 Australian-born women, aged 45-55 years and menstruating at baseline; they were interviewed annually over 8 years. The retention rate was 88% (n = 387). Part II: After 12 years of follow-up, 257 (57%) women returned for assessment and 224 agreed to undergo X-rays of their hands and knees. METHODS Part I: Annual fasting blood collection, physical measurements, and interviews including questions about bothersome aches or stiff joints in the previous 2 weeks. A score for this symptom was calculated from the product of the severity and frequency data. These data were analyzed using random-effects time-series regression models. Part II: X-rays were scored for evidence of osteoarthritis using a validated scale, by two investigators who were blinded to questionnaire results. RESULTS Part I: 'Aches and stiff joints' were the most commonly reported symptom and reporting increased over time in the longitudinal study. Variables significantly associated with reporting bothersome aches and stiff joints were high body mass index (BMI) (p Part II: The relationship between radiological osteoarthritis and symptom reports approached statistical significance (p = 0.06). Knee osteoarthritis was significantly associated with symptom reports (p = 0.008) but not hand osteoarthritis (p = 0.2). Menopausal status, BMI, employment status and depressed mood were all associated with the experience of bothersome aches and stiff joints. Aches and stiff joints, common in postmenopausal women, are not necessarily indicative of radiological osteoarthritis.

  6. Interaction between gut immunity and polysaccharides.

    Science.gov (United States)

    Huang, Xiaojun; Nie, Shaoping; Xie, Mingyong

    2017-09-22

    The human gut is colonized with a vast and diverse microbial ecosystem, and these bacteria play fundamental roles in the well being of our bodies. Gut-associated lymphoid tissues, the largest mucosal immune system, should never be overlooked for their profound effect in maintaining the host immunity. Therefore, we discussed the relationship between gut immunity and host health, primarily from two aspects: the homeostasis of gut microbiota, and the function of gut-associated lymphoid tissues. Polysaccharides, widely concerned as bioactive macromolecules in recent centuries, have been proved to benefit the intestinal health. Dietary polysaccharides can improve the ratio of probiotics, regulate the intestinal microenvironment like decreasing the gut pH, and stimulate the macrophages or lymphocytes in gut tissues to fight against diseases like cancer. Based on various experimental and clinical evidence, the impacts of dietary polysaccharides on intestinal health are summarized, in order to reveal the possible immunomodulatory mechanisms of polysaccharides.

  7. Efficient expression of functional (α6β22β3 AChRs in Xenopus oocytes from free subunits using slightly modified α6 subunits.

    Directory of Open Access Journals (Sweden)

    Carson Kai-Kwong Ley

    Full Text Available Human (α6β2(α4β2β3 nicotinic acetylcholine receptors (AChRs are essential for addiction to nicotine and a target for drug development for smoking cessation. Expressing this complex AChR is difficult, but has been achieved using subunit concatamers. In order to determine what limits expression of α6* AChRs and to efficiently express α6* AChRs using free subunits, we investigated expression of the simpler (α6β22β3 AChR. The concatameric form of this AChR assembles well, but is transported to the cell surface inefficiently. Various chimeras of α6 with the closely related α3 subunit increased expression efficiency with free subunits and produced pharmacologically equivalent functional AChRs. A chimera in which the large cytoplasmic domain of α6 was replaced with that of α3 increased assembly with β2 subunits and transport of AChRs to the oocyte surface. Another chimera replacing the unique methionine 211 of α6 with leucine found at this position in transmembrane domain 1 of α3 and other α subunits increased assembly of mature subunits containing β3 subunits within oocytes. Combining both α3 sequences in an α6 chimera increased expression of functional (α6β22β3 AChRs to 12-fold more than with concatamers. This is pragmatically useful, and provides insights on features of α6 subunit structure that limit its expression in transfected cells.

  8. Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate.

    Science.gov (United States)

    De Jongh, Cindy M; Verberk, Maarten M; Withagen, Carien E T; Jacobs, John J L; Rustemeyer, Thomas; Kezic, Sanja

    2006-06-01

    Little is known about cytokines involved in chronic irritant contact dermatitis. Individual cytokine profiles might explain at least part of the differences in the individual response to irritation. Our objective was to investigate the relation between baseline stratum corneum (SC) cytokine levels and the skin response to a single and a repeated irritation test. This study also aimed to determine changes in SC cytokine levels after repeated irritation. Transepidermal water loss (TEWL) and erythema were measured in 20 volunteers after single 24-hr exposure to 1% sodium lauryl sulfate (SLS), and during and after repeated exposure to 0.1% SLS over a 3-week period. SC cytokine levels were measured from an unexposed skin site and from the repeatedly exposed site. Interleukin (IL)-1alpha decreased by 30% after repeated exposure, while IL-1RA increased 10-fold and IL-8 increased fourfold. Baseline IL-1RA and IL-8 values were predictors of TEWL and erythema after single exposure (r = 0.55-0.61). 6 subjects showed barrier recovery during repeated exposure. Baseline IL-1RA and IL-8 levels are likely to be indicators of higher skin irritability after single exposure to SLS. Barrier repair in some of the subjects might explain the lack of agreement between the TEWL response after single and repeated irritation.

  9. Augmentation of skin response by exposure to a combination of allergens and irritants - a review

    DEFF Research Database (Denmark)

    Pedersen, Line Kynemund; Johansen, Jeanne Duus; Held, Elisabeth

    2004-01-01

    Clinical experimental studies on contact dermatitis (CD) often evaluate the effect of one allergen or one irritant at a time. In real life, the skin is often exposed to more allergens, more irritants or allergens and irritants in combination. This combined exposure may potentially influence irrit...

  10. The use of nanoencapsulation to decrease human skin irritation caused by capsaicinoids

    Directory of Open Access Journals (Sweden)

    Contri RV

    2014-02-01

    Full Text Available Renata V Contri,1 Luiza A Frank,2 Moacir Kaiser,1 Adriana R Pohlmann,1,3 Silvia S Guterres1,2 1Programa de Pós-Graduação em Ciências Farmacêuticas, 2Faculdade de Farmácia, 3Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil Abstract: Capsaicin, a topical analgesic used in the treatment of chronic pain, has irritant properties that frequently interrupt its use. In this work, the effect of nanoencapsulation of the main capsaicinoids (capsaicin and dihydrocapsaicin on skin irritation was tested in humans. Skin tolerance of a novel vehicle composed of chitosan hydrogel containing nonloaded nanocapsules (CH-NC was also evaluated. The chitosan hydrogel containing nanoencapsulated capsaicinoids (CH-NC-CP did not cause skin irritation, as measured by an erythema probe and on a visual scale, while a formulation containing free capsaicinoids (chitosan gel with hydroalcoholic solution [CH-ET-CP] and a commercially available capsaicinoids formulation caused skin irritation. Thirty-one percent of volunteers reported slight irritation one hour after application of CH-NC-CP, while moderate (46% [CH-ET-CP] and 23% [commercial product] and severe (8% [CH-ET-CP] and 69% [commercial product] irritation were described for the formulations containing free capsaicinoids. When CH-NC was applied to the skin, erythema was not observed and only 8% of volunteers felt slight irritation, which demonstrates the utility of the novel vehicle. A complementary in vitro skin permeation study showed that permeation of capsaicinoids through an epidermal human membrane was reduced but not prevented by nanoencapsulation. Keywords: chitosan, nanocapsules, capsaicinoids, skin irritation, skin permeation

  11. Impact of human milk bacteria and oligosaccharides on neonatal gut microbiota establishment and gut health.

    Science.gov (United States)

    Jost, Ted; Lacroix, Christophe; Braegger, Christian; Chassard, Christophe

    2015-07-01

    Neonatal gut microbiota establishment represents a crucial stage for gut maturation, metabolic and immunologic programming, and consequently short- and long-term health status. Human milk beneficially influences this process due to its dynamic profile of age-adapted nutrients and bioactive components and by providing commensal maternal bacteria to the neonatal gut. These include Lactobacillus spp., as well as obligate anaerobes such as Bifidobacterium spp., which may originate from the maternal gut via an enteromammary pathway as a novel form of mother-neonate communication. Additionally, human milk harbors a broad range of oligosaccharides that promote the growth and activity of specific bacterial populations, in particular, Bifidobacterium and Bacteroides spp. This review focuses on the diversity and origin of human milk bacteria, as well as on milk oligosaccharides that influence neonatal gut microbiota establishment. This knowledge can be used to develop infant formulae that more closely mimic nature's model and sustain a healthy gut microbiota. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. The Role of nAChR and Calcium Signaling in Pancreatic Cancer Initiation and Progression

    Energy Technology Data Exchange (ETDEWEB)

    Schaal, Courtney [Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612 (United States); Padmanabhan, Jaya [Department of Molecular Medicine and USF Health Byrd Alzheimer’s Institute, University of South Florida, 4001 E. Fletcher Ave., Tampa, FL 33612 (United States); Chellappan, Srikumar, E-mail: Srikumar.Chellappan@moffitt.org [Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612 (United States)

    2015-07-31

    Pancreatic cancer shows a strong correlation with smoking and the current therapeutic strategies have been relatively ineffective in improving the survival of patients. Efforts have been made over the past many years to understand the molecular events that drive the initiation and progression of pancreatic cancer, especially in the context of smoking. It has become clear that components of tobacco smoke not only initiate these cancers, especially pancreatic ductal adenocarcinomas (PDACs) through their mutagenic properties, but can also promote the growth and metastasis of these tumors by stimulating cell proliferation, angiogenesis, invasion and epithelial-mesenchymal transition. Studies in cell culture systems, animal models and human samples have shown that nicotinic acetylcholine receptor (nAChR) activation enhances these tumor-promoting events by channeling signaling through multiple pathways. In this context, signaling through calcium channels appear to facilitate pancreatic cancer growth by itself or downstream of nAChRs. This review article highlights the role of nAChR downstream signaling events and calcium signaling in the growth, metastasis as well as drug resistance of pancreatic cancer.

  13. The Role of nAChR and Calcium Signaling in Pancreatic Cancer Initiation and Progression

    International Nuclear Information System (INIS)

    Schaal, Courtney; Padmanabhan, Jaya; Chellappan, Srikumar

    2015-01-01

    Pancreatic cancer shows a strong correlation with smoking and the current therapeutic strategies have been relatively ineffective in improving the survival of patients. Efforts have been made over the past many years to understand the molecular events that drive the initiation and progression of pancreatic cancer, especially in the context of smoking. It has become clear that components of tobacco smoke not only initiate these cancers, especially pancreatic ductal adenocarcinomas (PDACs) through their mutagenic properties, but can also promote the growth and metastasis of these tumors by stimulating cell proliferation, angiogenesis, invasion and epithelial-mesenchymal transition. Studies in cell culture systems, animal models and human samples have shown that nicotinic acetylcholine receptor (nAChR) activation enhances these tumor-promoting events by channeling signaling through multiple pathways. In this context, signaling through calcium channels appear to facilitate pancreatic cancer growth by itself or downstream of nAChRs. This review article highlights the role of nAChR downstream signaling events and calcium signaling in the growth, metastasis as well as drug resistance of pancreatic cancer

  14. Grumbling Guts?

    Science.gov (United States)

    ... in the abdomen, along with changes in bowel habits. People with irritable bowel syndrome may have constipation, ... treatment that works best for you. Related Stories Power to the Pelvis Battling a Bulging Hernia Keeping ...

  15. Cutaneous irritancy of an ibuprofen medicated plaster in healthy volunteers.

    Science.gov (United States)

    Maganji, Manisha; Connolly, Mark P; Bhatt, Aomesh

    2018-04-01

    To assess the irritation and contact sensitization potential of a 200 mg ibuprofen medicated plaster. This double-blind, phase-1 placebo controlled study had two phases; the induction phase to evaluate the irritant potential of continuous application of the plaster, and the challenge phase to assess contact sensitivity (allergy). The cumulative irritancy potential was evaluated using an adaptation of the Shelanski method. Healthy adults (≥18 years of age) (N = 210) were treated simultaneously with one ibuprofen medicated and one placebo plaster applied in a randomized fashion to either the left or right side of the lower back. During the induction phase, plasters were applied on Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 and the final plaster removed on Day 22. At each scheduled visit plasters and applications sites were assessed for degree of adhesion and skin irritation (score of 1 = no irritation to 7 = strong reaction spreading beyond test sites), respectively. The challenge phase followed a two-week washout period. A plaster was applied on Day 36 for 48 h and assessment occurred on Days 38, 39, and 40. The mean cumulative irritation score during the induction phase was lower for the ibuprofen medicated plaster than the placebo plaster (0.32 vs. 1.23, respectively). Three (1.4%) subjects experience a dermal reaction of grade ≥3 for the ibuprofen medicated plaster compared with 27 (12.7%) for the placebo plaster. Following challenge with ibuprofen or placebo plasters, 12 subjects (6.2%) with the ibuprofen medicated plaster and four (2.2%) with the placebo plaster had skin reaction of assessment grade higher than the induction phase. One subject for the ibuprofen and two for the placebo plaster had reactions with grade >2. No subjects showed an increase in sensitization on Day 39 or 40 compared with Day 38. The findings indicate that the both the irritancy and contact sensitization of the ibuprofen medicated plaster is acceptable.

  16. First Foods and Gut Microbes

    DEFF Research Database (Denmark)

    Laursen, Martin Frederik; Bahl, Martin Iain; Michaelsen, Kim F.

    2017-01-01

    , are generally recognized to be of particular importance for the healthy development of children. While dietary changes are known to affect the adult gut microbiota, there is a gap in our knowledge on how the introduction of new dietary components into the diet of infants/young children affects the gut...... microbiota development. This perspective paper summarizes the currently very few studies addressing the effects of complementary diet on gut microbiota, and highlights the recent finding that transition to family foods greatly impacts the development of gut microbial diversity. Further, we discuss potential......(breast/formula). Consequently, the neonatal period and early infancy has attracted much attention. However, after this first period the gut microbial composition continues to develop until the age of 3 years, and these 1st years have been designated "a window of opportunity" for microbial modulation. The beginning and end...

  17. Hh pathway expression in human gut tissues and in inflammatory gut diseases

    NARCIS (Netherlands)

    Nielsen, Corinne M.; Williams, Jerrell; van den Brink, Gijs R.; Lauwers, Gregory Y.; Roberts, Drucilla J.

    2004-01-01

    Sonic hedgehog (Shh) directs early gut patterning via epithelial-mesenchymal signaling and remains expressed in endoderm-derived tissues into the adult period. In human adult gut epithelium SHH/SHH expression is strongest in basal layers, which suggests that SHH may function in the maintenance of

  18. [Gallbladder contractility in children with functional abdominal pain or irritable bowel syndrome].

    Science.gov (United States)

    Iwańczak, Franciszek; Siedlecka-Dawidko, Jolanta; Iwanczak, Barbara

    2013-07-01

    III Rome Criteria of functional gastrointestinal disorders in children, distinguished the disturbances with abdominal pain, to which irritable bowel syndrome, functional abdominal pains, functional dyspepsia and abdominal migraine were included. THE AIM OF THE STUDY was sonographic assessment of the gallbladder and its contractility in functional abdominal pain and irritable bowel syndrome in children. The study comprised 96 children aged 6 to 18 years, 59 girls and 37 boys. Depending on diagnosis, the children were divided into three groups. 38 children with functional abdominal pain constituted the first group, 26 children with irritable bowel syndrome were included to the second group, the third group consisted of 32 healthy children (control group). Diagnosis of functional abdominal pain and irritable bowel syndrome was made based on the III Rome Criteria. In irritable bowel syndrome both forms with diarrhea (13) and with constipation (13) were observed. Anatomy and contractility of the gallbladder were assessed by ultrasound examination. The presence of septum, wall thickness, thick bile, vesicle volume in fasting state and 30th and 60th minute after test meal were taken into consideration. Test meal comprised about 15% of caloric requirement of moderate metabolism. Children with bile stones and organic diseases were excluded from the study. Thickened vesicle wall and thick bile were present more frequently in children with irritable bowel syndrome and functional abdominal pain than in control group (p functional abdominal pain than in irritable bowel syndrome and control group (p = 0.003, p = 0.05). Vesicle contractility after test meal was greatest in children with functional abdominal pain. Evaluation of diminished (smaller than 30%) and enlarged (greater then 80%) gallbladder contractility at 30th and 60th minute after test meal demonstrated disturbances of contractility in children with irritable bowel syndrome and functional abdominal pain. In children

  19. Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Stanisavljević, S; Lukić, J; Momčilović, M; Miljković, M; Jevtić, B; Kojić, M; Golić, N; Mostarica Stojković, M; Miljković, D

    2016-06-01

    Gut microbiota and gut-associated lymphoid tissue have been increasingly appreciated as important players in pathogenesis of various autoimmune diseases, including multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis that can be induced with an injection of spinal cord homogenate emulsified in complete Freund's adjuvant in Dark Agouti (DA) rats, but not in Albino Oxford (AO) rats. In this study, mesenteric lymph nodes (MLN), Peyer's patches (PP) and gut microbiota were analysed in these two rat strains. There was higher proportion of CD4(+) T cells and regulatory T cells in non-immunised DA rats in comparison to AO rats. Also, DA rat MLN and PP cells were higher producers of pro-inflammatory cytokines interferon-γ and interleukin-17. Finally, microbial analyses showed that uncultivated species of Turicibacter and Atopostipes genus were exclusively present in AO rats, in faeces and intestinal tissue, respectively. Thus, it is clear that in comparison of an EAE-susceptible with an EAE-resistant strain of rats, various discrepancies at the level of gut associated lymphoid tissue, as well as at the level of gut microbiota can be observed. Future studies should determine if the differences have functional significance for EAE pathogenesis.

  20. Irritable Bowel Syndrome in a Population of African Patients

    Directory of Open Access Journals (Sweden)

    Sylvester Chuks Nwokediuko

    2012-01-01

    Full Text Available Background. Functional dyspepsia is the prototype functional gastrointestinal disorder. This study was designed to determine its prevalence, subtypes, and risk factors associated with the subtypes. Method. Patients with upper gastrointestinal symptoms who presented for endoscopy were administered a questionnaire containing the functional dyspepsia and irritable bowel syndrome modules of the Rome III diagnostic criteria. Results. Of 192 patients who had functional dyspepsia, epigastric pain syndrome, postprandial distress syndrome, and combination of the two subtypes accounted for 79.2%, 62.5%, and 50%, respectively. Multivariate analysis of the risk factors showed that independent predictors of postprandial distress syndrome were alcohol and irritable bowel syndrome while irritable bowel syndrome was independent predictor of epigastric pain syndrome. Alcohol, smoking, and use of nonsteroidal anti-inflammatory drugs were independent predictors of cooccurrence of postprandial distress syndrome and epigastric pain syndrome. Conclusion. Functional dyspepsia accounts for 62.5% of dyspepsia in a population of black African patients. Regarding symptomatology, epigastric pain syndrome, postprandial distress syndrome, and combination of the two subtypes account for 79.2%, 62.5%, and 50%, respectively. Risk factors for functional dyspepsia are irritable bowel syndrome, alcohol, smoking, and use of nonsteroidal anti-inflammatory drugs.

  1. Current irritability robustly related to current and prior anxiety in bipolar disorder.

    Science.gov (United States)

    Yuen, Laura D; Miller, Shefali; Wang, Po W; Hooshmand, Farnaz; Holtzman, Jessica N; Goffin, Kathryn C; Shah, Saloni; Ketter, Terence A

    2016-08-01

    Although current irritability and current/prior anxiety have been associated in unipolar depression, these relationships are less well understood in bipolar disorder (BD). We investigated relationships between current irritability and current/prior anxiety as well as other current emotions and BD illness characteristics. Outpatients referred to the Stanford Bipolar Disorders Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation. Prevalence and clinical correlates of current irritability and current/prior anxiety and other illness characteristics were examined. Among 497 BD outpatients (239 Type I, 258 Type II; 58.1% female; mean ± SD age 35.6 ± 13.1 years), 301 (60.6%) had baseline current irritability. Patients with versus without current irritability had significantly higher rates of current anxiety (77.1% versus 42.9%, p anxiety disorder (73.1% versus 52.6%, p anxiety than to current anhedonia, sadness, or euphoria (all p anxiety associations persisted across current predominant mood states. Current irritability was more robustly related to past anxiety than to all other assessed illness characteristics, including 1° family history of mood disorder, history of alcohol/substance use disorder, bipolar subtype, and current syndromal/subsyndromal depression (all p anxiety. Further studies are warranted to assess longitudinal clinical implications of relationships between irritability and anxiety in BD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. The Effect of Topical Local Anesthetics on Thermal Pain Sensitivity in Patients with Irritable Bowel Syndrome

    Directory of Open Access Journals (Sweden)

    Anthony Rodrigues

    2012-01-01

    Full Text Available Generalized hypersensitivity that extends into somatic areas is common in patients with irritable bowel syndrome (IBS. The sensitized state, particularly assessed by experimental methods, is known to persist even during remissions of clinical pain. It was hypothesized that disease-related nociceptive activity in the gut maintains a systemic-sensitized state. The present study evaluated responses to prolonged thermal stimuli maintained at constant temperature or constant pain intensity during stimulation. The effect of topically applied rectal lidocaine on heat sensitivity was also evaluated. The question is whether silencing potential intestinal neural activity (which may not always lead to a conscious pain experience with lidocaine attenuates sensitization of somatic areas. Tests were also performed where lidocaine was applied orally to control for systemic or placebo effects of the drug. The IBS subjects exhibited a greater sensitivity to somatic heat stimuli compared to controls; however, lidocaine had no discernible effect on sensitization in this sample of IBS patients, where most of the individuals did not have clinical pain on the day of testing.

  3. Disturbance of the gut microbiota in early-life selectively affects visceral pain in adulthood without impacting cognitive or anxiety-related behaviors in male rats.

    Science.gov (United States)

    O'Mahony, S M; Felice, V D; Nally, K; Savignac, H M; Claesson, M J; Scully, P; Woznicki, J; Hyland, N P; Shanahan, F; Quigley, E M; Marchesi, J R; O'Toole, P W; Dinan, T G; Cryan, J F

    2014-09-26

    Disruption of bacterial colonization during the early postnatal period is increasingly being linked to adverse health outcomes. Indeed, there is a growing appreciation that the gut microbiota plays a role in neurodevelopment. However, there is a paucity of information on the consequences of early-life manipulations of the gut microbiota on behavior. To this end we administered an antibiotic (vancomycin) from postnatal days 4-13 to male rat pups and assessed behavioral and physiological measures across all aspects of the brain-gut axis. In addition, we sought to confirm and expand the effects of early-life antibiotic treatment using a different antibiotic strategy (a cocktail of pimaricin, bacitracin, neomycin; orally) during the same time period in both female and male rat pups. Vancomycin significantly altered the microbiota, which was restored to control levels by 8 weeks of age. Notably, vancomycin-treated animals displayed visceral hypersensitivity in adulthood without any significant effect on anxiety responses as assessed in the elevated plus maze or open field tests. Moreover, cognitive performance in the Morris water maze was not affected by early-life dysbiosis. Immune and stress-related physiological responses were equally unaffected. The early-life antibiotic-induced visceral hypersensitivity was also observed in male rats given the antibiotic cocktail. Both treatments did not alter visceral pain perception in female rats. Changes in visceral pain perception in males were paralleled by distinct decreases in the transient receptor potential cation channel subfamily V member 1, the α-2A adrenergic receptor and cholecystokinin B receptor. In conclusion, a temporary disruption of the gut microbiota in early-life results in very specific and long-lasting changes in visceral sensitivity in male rats, a hallmark of stress-related functional disorders of the brain-gut axis such as irritable bowel disorder. Copyright © 2014 IBRO. Published by Elsevier Ltd. All

  4. Role of the normal gut microbiota.

    Science.gov (United States)

    Jandhyala, Sai Manasa; Talukdar, Rupjyoti; Subramanyam, Chivkula; Vuyyuru, Harish; Sasikala, Mitnala; Nageshwar Reddy, D

    2015-08-07

    Relation between the gut microbiota and human health is being increasingly recognised. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gut microbiota comprises of two major phyla, namely Bacteroidetes and Firmicutes. Though the gut microbiota in an infant appears haphazard, it starts resembling the adult flora by the age of 3 years. Nevertheless, there exist temporal and spatial variations in the microbial distribution from esophagus to the rectum all along the individual's life span. Developments in genome sequencing technologies and bioinformatics have now enabled scientists to study these microorganisms and their function and microbe-host interactions in an elaborate manner both in health and disease. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Several factors play a role in shaping the normal gut microbiota. They include (1) the mode of delivery (vaginal or caesarean); (2) diet during infancy (breast milk or formula feeds) and adulthood (vegan based or meat based); and (3) use of antibiotics or antibiotic like molecules that are derived from the environment or the gut commensal community. A major concern of antibiotic use is the long-term alteration of the normal healthy gut microbiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool.

  5. Supersymmetric GUTs and cosmology

    International Nuclear Information System (INIS)

    Lazarides, G.; Shafi, Q.

    1982-06-01

    By examining the behaviour of supersymmetric GUTs in the very early universe we find two classes of realistic models. In one of them supersymmetry is broken at or near the superheavy GUT scale. The cosmological implications of such models are expected to be similar to those of nonsupersymmetric GUTs. In the second class of models, the superheavy GUT scale is related to the supersymmetry breaking scale a la Witten. Two types of cosmological scenarios appear possible in this case, either with or without an intermediate (new) inflationary phase. They can be experimentally distinguished, since the former predicts an absence and the latter an observable number density of superheavy monopoles. A mechanism for generating baryon asymmetry in such models is pointed out. Further constraint on model building appears if global R invariance is employed to resolve the strong CP problem. (author)

  6. Involvement of Corticotropin-Releasing Factor and Receptors in Immune Cells in Irritable Bowel Syndrome

    Directory of Open Access Journals (Sweden)

    Mahanand Chatoo

    2018-02-01

    Full Text Available Irritable bowel syndrome (IBS is a common functional gastrointestinal disorder defined by ROME IV criteria as pain in the lower abdominal region, which is associated with altered bowel habit or defecation. The underlying mechanism of IBS is not completely understood. IBS seems to be a product of interactions between various factors with genetics, dietary/intestinal microbiota, low-grade inflammation, and stress playing a key role in the pathogenesis of this disease. The crosstalk between the immune system and stress in IBS mechanism is increasingly recognized. Corticotropin-releasing factor (CRF, a major mediator in the stress response, is involved in altered function in GI, including inflammatory processes, colonic transit time, contractile activity, defecation pattern, pain threshold, mucosal secretory function, and barrier functions. This mini review focuses on the recently establish local GI-CRF system, its involvement in modulating the immune response in IBS, and summarizes current IBS animal models and mapping of CRF, CRFR1, and CRFR2 expression in colon tissues. CRF and receptors might be a key molecule involving the immune and movement function via brain–gut axis in IBS.

  7. [Irritable bowel syndrome, levator ani syndrome, proctalgia fugax and chronic pelvic and perineal pain].

    Science.gov (United States)

    Watier, Alain; Rigaud, Jérôme; Labat, Jean-Jacques

    2010-11-01

    To define functional gastrointestinal pain, irritable bowel syndrome (IBS), levator ani syndrome, proctalgia fugax, the pathophysiology of these syndromes and the treatments that can be proposed. Review of articles published on the theme based on a Medline (PubMed) search and consensus conferences selected according to their scientific relevance. IBS is very common. Patients report abdominal pain and/or discomfort, bloating, and abnormal bowel habit (diarrhoea, constipation or both), in the absence of any structural or biochemical abnormalities. IBS has a complex, multifactorial pathophysiology, involving biological and psychosocial interactions resulting in dysregulation of the brain-gut axis associated with disorders of intestinal motility, hyperalgesia, immune disorders and disorders of the intestinal bacterial microflora and autonomic and hormonal dysfunction. Many treatments have been proposed, ranging from diet to pharmacology and psychotherapy. Patients with various types of chronic pelvic and perineal pain, especially those seen in urology departments, very often report associated IBS. This syndrome is also part of a global and integrated concept of pelviperineal dysfunction, avoiding a rigorous distinction between the posterior segment and the midline and anterior segments of the perineum. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  8. Efficacy of the low FODMAP diet for treating irritable bowel syndrome: the evidence to date

    Directory of Open Access Journals (Sweden)

    Nanayakkara WS

    2016-06-01

    Full Text Available Wathsala S Nanayakkara,1 Paula ML Skidmore,1 Leigh O'Brien,2 Tim J Wilkinson,3 Richard B Gearry,31Department of Human Nutrition, University of Otago, Dunedin, New Zealand; 2Dietary Specialists, Christchurch, New Zealand; 3Department of Medicine, University of Otago, Christchurch, New Zealand Abstract: This review summarizes the published clinical studies concerning the management of irritable bowel syndrome (IBS using restriction of Fermentable Oligosaccharide, Disaccharide, Monosaccharide, and Polyols in the diet (low FODMAP diet. In recent years, the data supporting low FODMAP diet for the management of IBS symptoms have emerged, including several randomized controlled trials, case-control studies, and other observational studies. Unlike most dietary manipulations tried in the past to alleviate gastrointestinal symptoms of IBS, all studies on low FODMAP diet have consistently shown symptomatic benefits in the majority of patients with IBS. However, dietary adherence by the patients and clear dietary intervention led by specialized dietitians appear to be vital for the success of the diet. Up to 86% of patients with IBS find improvement in overall gastrointestinal symptoms as well as individual symptoms such as abdominal pain, bloating, constipation, diarrhea, abdominal distention, and flatulence following the diet. FODMAP restriction reduces the osmotic load and gas production in the distal small bowel and the proximal colon, providing symptomatic relief in patients with IBS. Long-term health effects of a low FODMAP diet are not known; however, stringent FODMAP restriction is not recommended owing to risks of inadequate nutrient intake and potential adverse effects from altered gut microbiota. In conclusion, the evidence to date strongly supports the efficacy of a low FODMAP diet in the treatment of IBS. Further studies are required to understand any potential adverse effects of long-term restriction of FODMAPs. Keywords: irritable bowel

  9. Throat ache ans swelling of the neck: first symptoms of Lemierre's syndrome

    NARCIS (Netherlands)

    de Lange, J.; Ybema, A; Baas, E. M.

    2014-01-01

    Lemierre's syndrome, a thrombophlebitis of the internal jugular vein, is a rare disorder, usually caused by the microorganism Fusobacterium necrophorum. Throat ache and swelling of the neck are often the first symptoms. Without adequate treatment, Lemierre's syndrome may result in thrombosis of the

  10. Antioxidant activity and irritation property of venoms from Apis species.

    Science.gov (United States)

    Somwongin, Suvimol; Chantawannakul, Panuwan; Chaiyana, Wantida

    2018-04-01

    Pharmacological effects of bee venom has been reported, however, it has been restricted to the bee venom collected from European honey bee (Apis mellifera). The aim of the present study was to compare the antioxidant activities and irritation properties of venoms collected from four different Apis species in Thailand, which includes Apis cerena (Asian cavity nesting honeybee), Apis florea (dwarf honeybee), Apis dorsata (giant honeybee), and A. mellifera. Melittin content of each bee venom extracts was investigated by using high-performance liquid chromatography. Ferric reducing antioxidant power, 2, 2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid), and 1, 1-diphenyl-2-picrylhydrazyl assay were used to determine the antioxidant activity, whereas, hen's egg test chorioallantoic membrane assay was used to determine the irritation property of each bee venom extracts. Melittin was the major constituent in all bee venom extracts. The melittin content in A. dorsata, A. mellifera, A. florea, and A. cerena were 95.8 ± 3.2%, 76.5 ± 1.9%, 66.3 ± 8.6%, and 56.8 ± 1.8%, respectively. Bee venom extract from A. dorsata possessed the highest antioxidant activity with the inhibition of 41.1 ± 2.2% against DPPH, Trolox equivalent antioxidant capacity of 10.21 ± 0.74 mM Trolox/mg and equivalent concentration (EC 1 ) of 0.35 ± 0.02 mM FeSO 4 /mg. Bee venom extract from A. mellifera exhibited the highest irritation, followed by A. cerena, A. dorsata, and A. florea, respectively. Melittin was the compound responsible for the irritation property of bee venom extracts since it could induce severe irritation (irritation score was 13.7 ± 0.5, at the concentration of 2 mg/ml). The extract from A. dorsata which possessed the highest antioxidant activity showed no irritation up to the concentration of 0.1 mg/ml. Therefore, bee venom extract from A. dorsata at the concentration not more than 0.1 mg/ml would be suggested for using

  11. GUT Scale Fermion Mass Ratios

    International Nuclear Information System (INIS)

    Spinrath, Martin

    2014-01-01

    We present a series of recent works related to group theoretical factors from GUT symmetry breaking which lead to predictions for the ratios of quark and lepton Yukawa couplings at the unification scale. New predictions for the GUT scale ratios y μ /y s , y τ /y b and y t /y b in particular are shown and compared to experimental data. For this comparison it is important to include possibly large supersymmetric threshold corrections. Due to this reason the structure of the fermion masses at the GUT scale depends on TeV scale physics and makes GUT scale physics testable at the LHC. We also discuss how this new predictions might lead to predictions for mixing angles by discussing the example of the recently measured last missing leptonic mixing angle θ 13 making this new class of GUT models also testable in neutrino experiments

  12. Comparison of the effect of glycerol and triamcinolone acetonide on cumulative skin irritation in a randomized trial

    DEFF Research Database (Denmark)

    Andersen, Flemming; Hedegaard, Kathryn; Petersen, Thomas Kongstad

    2007-01-01

    BACKGROUND: So-called anti-irritants are added to cosmetic formulations because of their alleged beneficial effect on irritated skin. Documentation for these claims is often limited. However, glycerol has shown anti-irritant properties in experimentally induced irritation from sodium lauryl sulfate...... volunteers. METHODS: Irritation was induced by 3 daily arm washes for a week with 10% sodium lauryl sulfate on one arm and 30% NON on the other. To maintain irritation, for the next 12 days volunteers washed their arms twice daily with the irritants. Treatments were applied immediately after washing....... The treatments (including vehicle and no treatment) were randomized to sites using a Latin square design. The reactions were evaluated clinically and instrumentally. LIMITATIONS: Study was designed to only detect potent anti-irritants. CONCLUSION: Glycerol reduced the irritant effect of both sodium lauryl...

  13. Albumin infusion after reperfusion prevents gut ischemia-reperfusion-induced gut-associated lymphoid tissue atrophy.

    Science.gov (United States)

    Ikezawa, Fumie; Fukatsu, Kazuhiko; Moriya, Tomoyuki; Maeshima, Yoshinori; Okamoto, Koichi; Hara, Etsuko; Hiraide, Hoshio; Compher, Charlene W

    2006-01-01

    Our recent study clarified that gut ischemia-reperfusion (I/R) causes gut-associated lymphoid tissue (GALT) mass atrophy, a possible mechanism for increased morbidity of infectious complications after severe surgical insults. Because albumin administration reportedly reduces hemorrhagic shock-induced lung injury, we hypothesized that albumin treatment prevents GALT atrophy due to gut I/R. Male mice (n = 37) were randomized to albumin, normal saline, and sham groups. All groups underwent jugular vein catheter insertion. The albumin and normal saline groups underwent 75-minute occlusion of the superior mesenteric artery. During gut ischemia, all mice received normal saline infusions at 1.0 mL/h. The albumin group was given 5% bovine serum albumin in normal saline at 1.0 mL/h for 60 minutes after reperfusion, whereas the normal saline group received 0.9% sodium chloride at 1.0 mL/h. The sham group underwent laparotomy only. Mice were killed on day 1 or 7, and the entire small intestine was harvested. GALT lymphocytes were isolated and counted. Their phenotypes (alphabetaTCR, gammadeltaTCR, CD4, CD8, B220) were determined by flow cytometry. On day 1, the gut I/R groups showed significantly lower total lymphocyte and B cell numbers in Peyer's patches and the lamina propria than the sham group. However, the albumin infusion partially but significantly restored these cell numbers. On day 7, there were no significant differences in any of the parameters measured among the 3 groups. Albumin infusion after a gut ischemic insult may maintain gut immunity by preventing GALT atrophy.

  14. Gut Microbiota and Metabolic Disorders

    Directory of Open Access Journals (Sweden)

    Kyu Yeon Hur

    2015-06-01

    Full Text Available Gut microbiota plays critical physiological roles in the energy extraction and in the control of local or systemic immunity. Gut microbiota and its disturbance also appear to be involved in the pathogenesis of diverse diseases including metabolic disorders, gastrointestinal diseases, cancer, etc. In the metabolic point of view, gut microbiota can modulate lipid accumulation, lipopolysaccharide content and the production of short-chain fatty acids that affect food intake, inflammatory tone, or insulin signaling. Several strategies have been developed to change gut microbiota such as prebiotics, probiotics, certain antidiabetic drugs or fecal microbiota transplantation, which have diverse effects on body metabolism and on the development of metabolic disorders.

  15. Irritable bowel syndrome: the burden and unmet needs in Europe.

    LENUS (Irish Health Repository)

    Quigley, E M M

    2012-02-03

    Irritable bowel syndrome affects approximately 10-15% of the European population, although prevalence rates vary depending on the classification used and the country surveyed. This may be due to differences in patterns of medical care and diagnosis of the condition. Up to 70% of individuals with irritable bowel syndrome may not have been formally diagnosed. The disorder affects 1.5-3 times as many women as men and poses a significant economic burden in Europe, estimated at euro 700-euro 1600 per person per year. It also reduces quality of life and is associated with psychological distress, disturbed work and sleep, and sexual dysfunction. It is a chronic disorder, which affects many individuals for more than 10 years. Most patients are managed in primary care, although some are referred to gastroenterologists and other specialists. Patients with irritable bowel syndrome undergo more abdomino-pelvic surgery than the general population. We propose that a positive diagnosis of the condition may avoid the delay in diagnosis many patients experience. We conclude that, in Europe, there are significant unmet needs including lack of familiarity with irritable bowel syndrome, difficulties in diagnosis and lack of effective treatments for the multiple symptoms of the disorder. The development of pan-European guidelines for irritable bowel syndrome will benefit patients with this condition in Europe.

  16. Pengaruh Entertainment, Irritating dan Informativeness Iklan di Website di Kalangan Mahasiswa

    Directory of Open Access Journals (Sweden)

    Edy Supriyadi

    2010-09-01

    Full Text Available There are several advantages and disadvantages and advertising via the Internet. The appeal of advertising may also arise from given information element, the element of comfort but also sometimes lead to disturbing or irritation elements. The limited number of Internet users in Indonesia and the different backgrounds of individual Internet users in Indonesia certainly provide a different assessment of the advertisements contained on the Internet. There are 3 factors which was the starting point to explain how consumers interpret the value of advertising, namely: informativeness, entertainment and irritation. This research aims to discover whether there is a relationship between entertainment, informativeness, and irritation toward advertising values and whether there is a relationship between entertainment and advertising values toward attitude towards web advertising using statistics tools of path analysis and multiple regression. The research shows that there is a significant relationship between independent variables such as informativeness, entertainment and irritation simultaneously toward the advertising value but there are no significant relationship between entertainment and informativeness toward the advertising value individually.  In the other model there is a significant relationship between informativeness, irritation and advertising values with the attitude towards web advertising.

  17. The low-FODMAP diet for irritable bowel syndrome: Lights and shadows.

    Science.gov (United States)

    Molina-Infante, Javier; Serra, Jordi; Fernandez-Bañares, Fernando; Mearin, Fermín

    2016-02-01

    Irritable bowel syndrome (IBS) affects 10-15% of the western population. Drug therapy for this entity has shown limited efficacy. The low Fermentable Oligo-, Di-, Monosaccharides And Polyols (FODMAP) diet has recently emerged as an effective intervention for reducing gastrointestinal symptoms in IBS. Currently, several mechanistic studies have proven the rational basis of carbohydrate restriction. In addition, high-quality evidence (prospective studies and randomized controlled trials) from a variety of countries supports the high effectiveness of a low-FODMAP diet for IBS symptoms (70%), especially abdominal bloating, pain, and diarrhea. Importantly, this diet seems to be superior to a gluten-free diet for patients with non-celiac gluten sensitivity. The most controversial features of the low FODMAP diet are its short- and long-term limitations (a high level of restriction, the need for monitoring by an expert dietitian, potential nutritional deficiencies, significant gut microbiota reduction, lack of predictors of response), as well as the potential lack of advantage over alternative dietary, pharmacological and psychological interventions for IBS. Although liberalization of carbohydrate intake is recommended in the long-term, the reintroduction process remains to be clarified as, theoretically, global carbohydrate restriction is deemed to be necessary to avoid additive effects. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  18. The gut microbiota in type 2 diabetes

    DEFF Research Database (Denmark)

    Nielsen, Trine; Allin, Kristine Højgaard; Pedersen, Oluf

    2016-01-01

    The exploration of the gut microbiota has intensified within the past decade with the introduction of cultivation-independent methods. By investigation of the gut bacterial genes, our understanding of the compositional and functional capability of the gut microbiome has increased. It is now widely...... recognized that the gut microbiota has profound effect on host metabolism and recently changes in the gut microbiota have been associated with type 2 diabetes. Animal models and human studies have linked changes in the gut microbiota to the induction of low-grade inflammation, altered immune response......, and changes in lipid and glucose metabolism. Several factors have been identified that might affect the healthy microbiota, potentially inducing a dysbiotic microbiota associated with a disease state. This increased understanding of the gut microbiota might potentially contribute to targeted intervention...

  19. Menthol attenuates respiratory irritation and elevates blood cotinine in cigarette smoke exposed mice.

    Directory of Open Access Journals (Sweden)

    Michael A Ha

    Full Text Available Addition of menthol to cigarettes may be associated with increased initiation of smoking. The potential mechanisms underlying this association are not known. Menthol, likely due to its effects on cold-sensing peripheral sensory neurons, is known to inhibit the sensation of irritation elicited by respiratory irritants. However, it remains unclear whether menthol modulates cigarette smoke irritancy and nicotine absorption during initial exposures to cigarettes, thereby facilitating smoking initiation. Using plethysmography in a C57Bl/6J mouse model, we examined the effects of L-menthol, the menthol isomer added to cigarettes, on the respiratory sensory irritation response to primary smoke irritants (acrolein and cyclohexanone and smoke of Kentucky reference 2R4 cigarettes. We also studied L-menthol's effect on blood levels of the nicotine metabolite, cotinine, immediately after exposure to cigarette smoke. L-menthol suppressed the irritation response to acrolein with an apparent IC₅₀ of 4 ppm. Suppression was observed even at acrolein levels well above those necessary to produce a maximal response. Cigarette smoke, at exposure levels of 10 mg/m³ or higher, caused an immediate and marked sensory irritation response in mice. This response was significantly suppressed by L-menthol even at smoke concentrations as high as 300 mg/m³. Counterirritation by L-menthol was abolished by treatment with a selective inhibitor of Transient Receptor Potential Melastatin 8 (TRPM8, the neuronal cold/menthol receptor. Inclusion of menthol in the cigarette smoke resulted in roughly a 1.5-fold increase in plasma cotinine levels over those observed in mice exposed to smoke without added menthol. These findings document that, L-menthol, through TRPM8, is a strong suppressor of respiratory irritation responses, even during highly noxious exposures to cigarette smoke or smoke irritants, and increases blood cotinine. Therefore, L-menthol, as a cigarette additive, may

  20. Development of radiohalogenated muscarinic ligands for the in vivo imaging of m-AChR by nuclear medicine techniques

    Energy Technology Data Exchange (ETDEWEB)

    McPherson, D.W.; Luo, H.; Knapp, F.F. Jr.

    1994-06-01

    Alterations in the density of acetylcholinergic muscarinic receptors (m-AChR) have been observed in various dementias. This has spurred interest in the development of radiohalogenated ligands which can be used for the non-invasive in vivo detection of m-AChR by nuclear medicine techniques. We have developed a new ligand 1-azabicyclo[2.2.2]oct-3-yl ({alpha}-hydroxy-{alpha}-(1-iodo-1-propen-3-yl)-{alpha}-phenylacetate (IQNP,12) which demonstrates high affinity for the muscarinic receptor. When labeled with radioiodine it has been shown to be selective and specific for m-ACHR. Initial studies on the separation and in vivo evaluation of the various isomers of IQNP have shown that the stereochemistry of the chiral centers and the configuration around the double bond play an important role in m-AChR subtype specificity. In vivo evaluation of these stereoisomers demonstrate that E-(R,R)-IQNP has a high affinity for the M{sub 1} muscarinic subtype while Z-(R,R)-IQNP demonstrate a high affinity for M{sub 1} and M{sub 2} receptor subtypes. These data demonstrate IQNP (12) has potential for use in the non-evasive in vivo detection of m-AChR by single photon emission computed tomography (SPECT). A brominated analogue, ``BrQNP,`` in which the iodine has been replaced by a bromine atom, has also been prepared and was shown to block the in vivo uptake of IQNP in the brain and heart and therefore has potential for positron emission tomographic (PET) studies of m-AChR.

  1. A retrospective analysis of in vivo eye irritation, skin irritation and skin sensitisation studies with agrochemical formulations: Setting the scene for development of alternative strategies.

    Science.gov (United States)

    Corvaro, M; Gehen, S; Andrews, K; Chatfield, R; Macleod, F; Mehta, J

    2017-10-01

    Analysis of the prevalence of health effects in large scale databases is key in defining testing strategies within the context of Integrated Approaches on Testing and Assessment (IATA), and is relevant to drive policy changes in existing regulatory toxicology frameworks towards non-animal approaches. A retrospective analysis of existing results from in vivo skin irritation, eye irritation, and skin sensitisation studies on a database of 223 agrochemical formulations is herein published. For skin or eye effects, high prevalence of mild to non-irritant formulations (i.e. per GHS, CLP or EPA classification) would generally suggest a bottom-up approach. Severity of erythema or corneal opacity, for skinor eye effects respectively, were the key drivers for classification, consistent with existing literature. The reciprocal predictivity of skin versus eye irritation and the good negative predictivity of the GHS additivity calculation approach (>85%) provided valuable non-testing evidence for irritation endpoints. For dermal sensitisation, concordance on data from three different methods confirmed the high false negative rate for the Buehler method in this product class. These results have been reviewed together with existing literature on the use of in vitro alternatives for agrochemical formulations, to propose improvements to current regulatory strategies and to identify further research needs. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Does Your Patient's Urine Turns Dark? Alkaptonuria and Low Back Ache: A Literature Review.

    Science.gov (United States)

    Kanniyan, Kalaivanan; Pathak, Aditya C; Dhammi, Ish Kumar; Jain, Anil Kumar

    2014-01-01

    Alkaptonuria is a very rare inborn error of amino acid metabolism due to deficient homogentisic acid (HGA) oxidase enzyme leading to accumulation of HGA in plasma, cartilage, other tissues of human body and its excretion in urine. It has both systemic and peripheral signs and symptoms. Though low back is a common symptom of alkaptonuria but, in the absence of ochronosis it is rare. Alkaptonuria itself is very rare occurrence with no specific treatment option available to reverse the effect as yet. A 38-year-old male, embroidery worker presented with chronic low back ache with history of staining of clothes in infancy. Later on laboratory and the radiological investigation patient was diagnosed to have alkaptonuria without ochronosis. No other systemic manifestation was present. Patient was treated conservatively and responded well. Though alkaptonuria is a very rare disease, and the occurrence of low back-ache in absence of ochronosis is much rarer. One must be aware of this inborn error of metabolism. Early diagnosis though being "diagnosis of exclusion" for low back-ache, high index of suspicion is advantageous as symptomatic treatment of the alkaptonuria can be initiated and evaluation of other systemic organs can be done in early stages itself.

  3. Early Life Experience and Gut Microbiome: The Brain-Gut-Microbiota Signaling System.

    Science.gov (United States)

    Cong, Xiaomei; Henderson, Wendy A; Graf, Joerg; McGrath, Jacqueline M

    2015-10-01

    Over the past decades, advances in neonatal care have led to substantial increases in survival among preterm infants. With these gains, recent concerns have focused on increases in neurodevelopment morbidity related to the interplay between stressful early life experiences and the immature neuroimmune systems. This interplay between these complex mechanisms is often described as the brain-gut signaling system. The role of the gut microbiome and the brain-gut signaling system have been found to be remarkably related to both short- and long-term stress and health. Recent evidence supports that microbial species, ligands, and/or products within the developing intestine play a key role in early programming of the central nervous system and regulation of the intestinal innate immunity. The purpose of this state-of-the-science review is to explore the supporting evidence demonstrating the importance of the brain-gut-microbiota axis in regulation of early life experience. We also discuss the role of gut microbiome in modulating stress and pain responses in high-risk infants. A conceptual framework has been developed to illustrate the regulation mechanisms involved in early life experience. The science in this area is just beginning to be uncovered; having a fundamental understanding of these relationships will be important as new discoveries continue to change our thinking, leading potentially to changes in practice and targeted interventions.

  4. Postanaesthetic tear production and ocular irritation in cats.

    Science.gov (United States)

    Peche, N; Köstlin, R; Reese, S; Pieper, K

    2015-01-01

    General anaesthesia significantly reduces tear production and normal values are not immediately re-established on ending anaesthesia. Therefore, adequate protection of the cornea has to be assured during the perianaesthetic period. There are various methods available, including taping of the eyelids and the application of eye ointments, gels and drops. In human medicine studies, different formulations were found to induce signs of ocular irritation. The aim of the present study was to determine tear production in cats after general anaesthesia, and to identify possible causes of irritation. Tear production was determined in 41 cats after general anaesthesia and eyes were examined for signs of irritation. Two different anaesthetic protocols were used. To protect the cornea, an ointment and gel were applied to the right and left eyes, respectively. Postoperatively, tear production was significantly reduced for 6 hours and 18 hours in the right and left eyes, respectively. Two hours after anaesthesia, blepharospasm of the right eye was observed in 92.7% (n = 38) of the cats. In contrast, the left eye was always held open. This study demonstrated that tear production in cats is significantly decreased both during and after anaesthesia. The degree of reduction was independent of the anaesthetic protocol. Both the eye ointment and gel proved effective in protecting the corneal surface. However, eye gel use is recommended because the eye ointment consistently caused an irritation comparable to the foreign-body sensation reported in humans.

  5. [Children's and adolescent's use of medicine for aches and psychological problems: secular trends from 1988 to 2006.

    DEFF Research Database (Denmark)

    Holstein, Bjørn; Andersen, Anette; Due, Pernille

    2009-01-01

    INTRODUCTION: Medicine use for aches and psychological problems is common among adolescents. Medicines are toxic and may have harmful side effects. It is therefore important to study change over time and patterns of medicine use. The objective of this paper is to describe self-reported medicine use...... for headaches, stomach-aches, difficulties in falling asleep, and nervousness among 11-, 13-, and 15-year-old boys and girls from 1968 to 2006. MATERIAL AND METHODS: The data material is 6 comparable and representative cross-sectional studies of 11-, 13-, and 15-year-olds from 1988, 1991, 1994, 1998, 2002......: There was a significant increase in 11-, 13-, and 15-year-old student's use of medicine for aches and psychological problems from 1988 to 2006. In the same period, there was a decrease in the prevalence of students who reported pains monthly. Udgivelsesdato: 2009-Jan-5...

  6. Unraveling the ties between irritable bowel syndrome and intestinal microbiota.

    Science.gov (United States)

    Hong, Sung Noh; Rhee, Poong-Lyul

    2014-03-14

    Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorder. It is a multifactorial disorder. Intestinal microbiota may cause the pathogenesis of IBS by contributing to abnormal gastrointestinal motility, low-grade inflammation, visceral hypersensitivity, communication in the gut-brain axis, and so on. Previous attempts to identify the intestinal microbiota composition in IBS patients have yielded inconsistent and occasionally contradictory results. This inconsistency may be due to the differences in the molecular techniques employed, the sample collection and handling methods, use of single samples that are not linked to fluctuating symptoms, or other factors such as patients' diets and phenotypic characterizations. Despite these difficulties, previous studies found that the intestinal microbiota in some IBS patients was completely different from that in healthy controls, and there does appear to be a consistent theme of Firmicutes enrichment and reduced abundance of Bacteroides. Based on the differences in intestinal microbiota composition, many studies have addressed the roles of microbiota-targeted treatments, such as antibiotics and probiotics, in alleviating certain symptoms of IBS. This review summarizes the current knowledge of the associations between intestinal microbiota and IBS as well as the possible modes of action of intestinal microbiota in the pathogenesis of IBS. Improving the current level of understanding of host-microbiota interactions in IBS is important not only for determining the role of intestinal microbiota in IBS pathogenesis but also for therapeutic modulation of the microbiota.

  7. An approach for evaluating the respiratory irritation of mixtures: application to metalworking fluids.

    Science.gov (United States)

    Schaper, M M; Detwiler-Okabayashi, K A

    1995-01-01

    Recently, the sensory and pulmonary irritating properties of ten metalworking fluids (MWF) were assessed using a mouse bioassay. Relative potency of the MWFs was estimated, but it was not possible to identify the component(s) responsible for the the respiratory irritation induced by each MWF. One of the ten fluids, MWF "ET", produced sensory and pulmonary irritation in mice, and it was of moderate potency in comparison to the other nine MWFs. MWF "E" had three major components: tall oil fatty acids (TOFA), sodium sulfonate (SA), and paraffinic oil (PO). In the present study, the sensory and pulmonary irritating properties of these individual components of MWF "E" were evaluated. Mixtures of the three components were also prepared and similarly evaluated. This analysis revealed that the sensory irritation from MWF "E" was largely due to TOFA, whereas SA produced the pulmonary irritation observed with MWF "E". Both TOFA and SA were more potent irritants than was MWF "E", and the potency of TOFA and/or SA was diminished through combination with PO. There was no evidence of synergism of the components when combined to form MWF "E". This approach for identifying the biologically "active" component(s) in a mixture should be useful for other MWFs. Furthermore, the approach should be easily adapted for other applications involving concerns with mixtures.

  8. Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate

    NARCIS (Netherlands)

    de Jongh, Cindy M.; Verberk, Maarten M.; Withagen, Carien E. T.; Jacobs, John J. L.; Rustemeyer, Thomas; Kezic, Sanja

    2006-01-01

    Little is known about cytokines involved in chronic irritant contact dermatitis. Individual cytokine profiles might explain at least part of the differences in the individual response to irritation. Our objective was to investigate the relation between baseline stratum corneum (SC) cytokine levels

  9. A tick gut protein with fibronectin III domains aids Borrelia burgdorferi congregation to the gut during transmission

    NARCIS (Netherlands)

    Narasimhan, Sukanya; Coumou, Jeroen; Schuijt, Tim J.; Boder, Eric; Hovius, Joppe W.; Fikrig, Erol

    2014-01-01

    Borrelia burgdorferi transmission to the vertebrate host commences with growth of the spirochete in the tick gut and migration from the gut to the salivary glands. This complex process, involving intimate interactions of the spirochete with the gut epithelium, is pivotal to transmission. We utilized

  10. Aging of oxygen and hydrogen plasma discharge treated a-C:H and ta-C coatings

    Energy Technology Data Exchange (ETDEWEB)

    Bachmann, Svenja [Physics of Surfaces, Institute of Materials Science, Technische Universität Darmstadt, Alarich-Weiss-Str. 16, 64287 Darmstadt (Germany); BMW Group, Hufelandstraße 4, 80788 Munich (Germany); Schulze, Marcus [Physics of Surfaces, Institute of Materials Science, Technische Universität Darmstadt, Alarich-Weiss-Str. 16, 64287 Darmstadt (Germany); Center of Smart Interfaces, Technische Universität Darmstadt, Alarich-Weiss-Str. 10, 64287 Darmstadt (Germany); Morasch, Jan [Institute of Materials Science, Technische Universität Darmstadt, Surface Science Division, Jovanka-Bonschits-Straße 2, 64287 Darmstadt (Germany); Hesse, Sabine [Physics of Surfaces, Institute of Materials Science, Technische Universität Darmstadt, Alarich-Weiss-Str. 16, 64287 Darmstadt (Germany); Center of Smart Interfaces, Technische Universität Darmstadt, Alarich-Weiss-Str. 10, 64287 Darmstadt (Germany); Hussein, Laith [Eduard-Zintl-Institut, Department of Chemistry, Technische Universität Darmstadt, Alarich-Weiss-Str. 12, 64287, Darmstadt (Germany); Krell, Lisa; Schnagl, Johann [BMW Group, Hufelandstraße 4, 80788 Munich (Germany); Stark, Robert W. [Physics of Surfaces, Institute of Materials Science, Technische Universität Darmstadt, Alarich-Weiss-Str. 16, 64287 Darmstadt (Germany); Center of Smart Interfaces, Technische Universität Darmstadt, Alarich-Weiss-Str. 10, 64287 Darmstadt (Germany); and others

    2016-05-15

    Highlights: • The water CA of O{sub 2} and H{sub 2} plasma treated a-C:H and ta-C changes from hydrophillic to hydrophobic on aging. • XPS study indicates that the decrease in surface energy of plasma treated a-C:H and ta-C could be due to adsorption of organic component from air. • The COFLFM of O{sub 2} and H{sub 2} plasma treated a-C:H and ta-C decreased upon aging. • The COF of glycerol lubricated ta-C showed no sign of change upon aging. - Abstract: Surface modification with gas plasma is an efficient and easy way to improve the surface energy and the tribological behavior of diamond-like carbon (DLC) coatings, e.g., in biomedical implants or as protective coatings. However, the long-term performance of the plasma treated DLC coatings is not fully clear. We thus studied the long-term stability of two kinds of DLC coatings, namely (a) hydrogenated amorphous carbon (a-C:H) and (b) tetrahedral amorphous carbon (ta-C) treated at different radio frequency (RF) power and time of oxygen (O{sub 2}) and hydrogen (H{sub 2}) plasma. Their surface properties, e.g. surface wettability, structure and tribological behavior, were studied at regular intervals for a period of two months using contact angle goniometer, Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), lateral force microscopy (LFM) and ball on disc apparatus. The surface energy of both the coatings decreased upon aging. The higher the RF power and time of treatment, the higher was the hydrophobicity upon aging. XPS analysis showed that the increase in hydrophobicity could be due to adsorption of unavoidable volatile organic components in the atmosphere. The H{sub 2} plasma treated ta-C was capable of rearranging its structural bonds upon aging. The nano-friction measurements by LFM showed that the coefficient of friction of plasma treated a-C:H and ta-C decreased upon aging. The results indicate that the surface properties of plasma treated a‐C:H and ta‐C are not stable on long-term and are

  11. String GUTs

    International Nuclear Information System (INIS)

    Aldazabal, G.; Ibanez, L.E.; Uranga, A.M.

    1995-01-01

    Standard SUSY-GUTs such as those based on SU(5) or SO(10) lead to predictions for the values of α s and sin 2 θ W in amazing agreement with experiment. In this article we investigate how these models may be obtained from string theory, thus bringing them into the only known consistent framework for quantum gravity. String models with matter in standard GUT representations require the realization of affine Lie algebras at higher levels. We start by describing some methods to build level k=2 symmetric orbifold string models with gauge groups SU(5) or SO(10). We present several examples and identify generic features of the type of models constructed. Chiral fields appropriate to break the symmetry down to the standard model generically appear in the massless spectrum. However, unlike in standard SUSY-GUTs, they often behave as string moduli, i.e., they do not have self-couplings. We also discuss briefly the doublet-triplet Higgs splitting. We find that, in some models, built-in sliding-singlet type of couplings exist. (orig.)

  12. Gut microbiota sustains hematopoiesis

    DEFF Research Database (Denmark)

    Theilgaard-Mönch, Kim

    2017-01-01

    In this issue of Blood, Josefsdottir et al provide substantial evidence that commensal gut microbes regulate and sustain normal steady-state hematopoiesis.1......In this issue of Blood, Josefsdottir et al provide substantial evidence that commensal gut microbes regulate and sustain normal steady-state hematopoiesis.1...

  13. Gut dysbiosis and detection of "live gut bacteria" in blood of Japanese patients with type 2 diabetes.

    Science.gov (United States)

    Sato, Junko; Kanazawa, Akio; Ikeda, Fuki; Yoshihara, Tomoaki; Goto, Hiromasa; Abe, Hiroko; Komiya, Koji; Kawaguchi, Minako; Shimizu, Tomoaki; Ogihara, Takeshi; Tamura, Yoshifumi; Sakurai, Yuko; Yamamoto, Risako; Mita, Tomoya; Fujitani, Yoshio; Fukuda, Hiroshi; Nomoto, Koji; Takahashi, Takuya; Asahara, Takashi; Hirose, Takahisa; Nagata, Satoru; Yamashiro, Yuichiro; Watada, Hirotaka

    2014-08-01

    Mounting evidence indicates that the gut microbiota are an important modifier of obesity and diabetes. However, so far there is no information on gut microbiota and "live gut bacteria" in the systemic circulation of Japanese patients with type 2 diabetes. Using a sensitive reverse transcription-quantitative PCR (RT-qPCR) method, we determined the composition of fecal gut microbiota in 50 Japanese patients with type 2 diabetes and 50 control subjects, and its association with various clinical parameters, including inflammatory markers. We also analyzed the presence of gut bacteria in blood samples. The counts of the Clostridium coccoides group, Atopobium cluster, and Prevotella (obligate anaerobes) were significantly lower (P blood at a significantly higher rate in diabetic patients than in control subjects (28% vs. 4%, P type 2 diabetes as assessed by RT-qPCR. The high rate of gut bacteria in the circulation suggests translocation of bacteria from the gut to the bloodstream. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  14. Activation of functional α7-containing nAChRs in hippocampal CA1 pyramidal neurons by physiological levels of choline in the presence of PNU-120596.

    Directory of Open Access Journals (Sweden)

    Bopanna I Kalappa

    2010-11-01

    Full Text Available The level of expression of functional α7-containing nicotinic acetylcholine receptors (nAChRs in hippocampal CA1 pyramidal neurons is believed to be very low compared to hippocampal CA1 interneurons, and for many years this expression was largely overlooked. However, high densities of expression of functional α7-containing nAChRs in CA1 pyramidal neurons may not be necessary for triggering important cellular and network functions, especially if activation of α7-containing nAChRs occurs in the presence of positive allosteric modulators such as PNU-120596.An approach previously developed for α7-containing nAChRs expressed in tuberomammillary neurons was applied to investigate functional CA1 pyramidal α7-containing nAChRs using rat coronal hippocampal slices and patch-clamp electrophysiology. The majority (∼71% of tested CA1 pyramidal neurons expressed low densities of functional α7-containing nAChRs as evidenced by small whole-cell responses to choline, a selective endogenous agonist of α7 nAChRs. These responses were potentiated by PNU-120596, a novel positive allosteric modulator of α7 nAChRs. The density of functional α7-containing nAChRs expressed in CA1 pyramidal neurons (and thus, the normalized net effect of activation, i.e., response net charge per unit of membrane capacitance per unit of time was estimated to be ∼5% of the density observed in CA1 interneurons. The results of this study demonstrate that despite low levels of expression of functional pyramidal α7-containing nAChRs, physiological levels of choline (∼10 µM are sufficient to activate these receptors and transiently depolarize and even excite CA1 pyramidal neurons in the presence of PNU-120596. The observed effects are possible because in the presence of 10 µM choline and 1-5 µM PNU-120596, a single opening of an individual pyramidal α7-containing nAChR ion channel appears to transiently depolarize (∼4 mV the entire pyramidal neuron and occasionally

  15. Irritability and Parenting Styles in Adolescents With Attention-Deficit/Hyperactivity Disorder: A Controlled Study.

    Science.gov (United States)

    Uçar, Halit Necmi; Vural, Ayşe Pınar

    2018-04-17

    Attention-deficit/hyperactivity disorder (ADHD) affects functioning of the family, decreasing interactions and loyalty and increasing conflict between adolescents with ADHD and their families. Irritable mood and difficulties with emotional dysregulation are common in children with ADHD. The objective of the current study was to assess levels of irritability in adolescents with ADHD using self- and parent-report scales, and investigate the relationship between irritability levels and parental attitudes. A total of 47 adolescents with ADHD and 39 adolescents with typical development participated in the current study. Findings demonstrated that higher levels of parent-reported irritability were associated with decreased egalitarian attitudes in the ADHD group. Although other parental attitudes were not associated with self- and parent-reported irritability, evaluation of the relationship between parental attitudes and irritability in adolescents with ADHD, which can guide diagnosis and treatment of ADHD, is of critical importance. [Journal of Psychosocial Nursing and Mental Health Services, xx(x), xx-xx.]. Copyright 2018, SLACK Incorporated.

  16. Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through α7nAChR+ splenocytes.

    Science.gov (United States)

    Inoue, Tsuyoshi; Abe, Chikara; Sung, Sun-Sang J; Moscalu, Stefan; Jankowski, Jakub; Huang, Liping; Ye, Hong; Rosin, Diane L; Guyenet, Patrice G; Okusa, Mark D

    2016-05-02

    The nervous and immune systems interact in complex ways to maintain homeostasis and respond to stress or injury, and rapid nerve conduction can provide instantaneous input for modulating inflammation. The inflammatory reflex referred to as the cholinergic antiinflammatory pathway regulates innate and adaptive immunity, and modulation of this reflex by vagus nerve stimulation (VNS) is effective in various inflammatory disease models, such as rheumatoid arthritis and inflammatory bowel disease. Effectiveness of VNS in these models necessitates the integration of neural signals and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. Here, we sought to determine whether electrical stimulation of the vagus nerve attenuates kidney ischemia-reperfusion injury (IRI), which promotes the release of proinflammatory molecules. Stimulation of vagal afferents or efferents in mice 24 hours before IRI markedly attenuated acute kidney injury (AKI) and decreased plasma TNF. Furthermore, this protection was abolished in animals in which splenectomy was performed 7 days before VNS and IRI. In mice lacking α7nAChR, prior VNS did not prevent IRI. Conversely, adoptive transfer of VNS-conditioned α7nAChR splenocytes conferred protection to recipient mice subjected to IRI. Together, these results demonstrate that VNS-mediated attenuation of AKI and systemic inflammation depends on α7nAChR-positive splenocytes.

  17. Irritability, Externalizing, and Internalizing Psychopathology in Adolescence: Cross-Sectional and Longitudinal Associations and Moderation by Sex.

    Science.gov (United States)

    Humphreys, Kathryn L; Schouboe, Sophie N F; Kircanski, Katharina; Leibenluft, Ellen; Stringaris, Argyris; Gotlib, Ian H

    2018-04-18

    Irritability is a common feature of many psychiatric disorders, including both externalizing and internalizing disorders. There is little research, however, examining associations between irritability and these symptom domains, particularly during the important developmental period of adolescence, characterized by sex differences in the prevalence of disorders. We examined the cross-sectional associations between irritability, measured with the Affective Reactivity Index, and symptoms of externalizing and internalizing domains of psychopathology, measured with the Youth Self Report, in a volunteer community sample (N = 183) of 9- to 13-year-old (M = 11.39, SD = 1.07) boys and girls (37% White/Caucasian, 8% Asian, 11% Hispanic, 8% African American, 2% Native American, 2% Pacific Islander, 28% Other, and 3% not reported). A subset of the sample (n = 112) provided data at a 2-year follow-up, used to extend these associations. There were no sex differences in levels of irritability; however, the associations between irritability and symptom domains were moderated by sex. Specifically, in girls, irritability was associated equally with externalizing and internalizing symptoms. In contrast, in boys, irritability was associated more strongly with externalizing symptoms than with internalizing symptoms. Thus, across both sexes, irritability was moderately associated with externalizing symptoms, but the association between irritability and internalizing symptoms was stronger in girls than in boys. At follow-up, sex moderated the association between baseline irritability and later externalizing and internalizing symptoms. These findings indicate that irritability is associated with both externalizing and internalizing symptoms in early adolescence and that irritability is associated with internalizing symptoms more strongly in girls than in boys.

  18. Irritability Trajectories, Cortical Thickness, and Clinical Outcomes in a Sample Enriched for Preschool Depression.

    Science.gov (United States)

    Pagliaccio, David; Pine, Daniel S; Barch, Deanna M; Luby, Joan L; Leibenluft, Ellen

    2018-05-01

    Cross-sectional, longitudinal, and genetic associations exist between irritability and depression. Prior studies have examined developmental trajectories of irritability, clinical outcomes, and associations with child and familial depression. However, studies have not integrated neurobiological measures. The present study examined developmental trajectories of irritability, clinical outcomes, and cortical structure among preschoolers oversampled for depressive symptoms. Beginning at 3 to 5 years old, a sample of 271 children enriched for early depressive symptoms were assessed longitudinally by clinical interview. Latent class mixture models identified trajectories of irritability severity. Risk factors, clinical outcomes, and cortical thickness were compared across trajectory classes. Cortical thickness measures were extracted from 3 waves of magnetic resonance imaging at 7 to 12 years of age. Three trajectory classes were identified among these youth: 53.50% of children exhibited elevated irritability during preschool that decreased longitudinally, 30.26% exhibited consistently low irritability, and 16.24% exhibited consistently elevated irritability. Compared with other classes, the elevated irritability class exhibited higher rates of maternal depression, early life adversity, later psychiatric diagnoses, and functional impairment. Further, elevated baseline irritability predicted later depression beyond adversity and personal and maternal depression history. The elevated irritability class exhibited a thicker cortex in the left superior frontal and temporal gyri and the right inferior parietal lobule. Irritability manifested with specific developmental trajectories in this sample enriched for early depression. Persistently elevated irritability predicted poor psychiatric outcomes, higher risk for later depression, and decreased overall function later in development. Greater frontal, temporal, and parietal cortical thickness also was found, providing neural

  19. An analysis of human response to the irritancy of acetone vapors

    NARCIS (Netherlands)

    Arts, J.H.E.; Mojet, J.; Gemert, L.J. van; Emmen, H.H.; Lammers, J.H.C.M.; Marquart, J.; Woutersen, R.A.; Feron, V.J.

    2002-01-01

    Studies on the irritative effects of acetone vapor in humans and experimental animals have revealed large differences in the lowest acetone concentration found to be irritative to the respiratory tract and eyes. This has brought on much confusion in the process of setting occupational exposure

  20. IRRITABLE BOWEL SYNDROME IN CHILDREN: DIAGNOSTICS AND MODERN APPROACHES TO THERAPY

    Directory of Open Access Journals (Sweden)

    S.Yu. Tereshchenko

    2006-01-01

    Full Text Available In the article modern data on prevalence, diagnostic criteria and approaches to the treatment of irritable bowel in children are presented. The issues of the terminology and classification of recurrent abdominal pains in children are clarified, the basic pathophysiological mechanisms of the disease are indicated. Particular emphasis has been placed on the efficient therapy of the different clinical variants of irritable bowel syndrome. The role of modern spasmolytic drugs in the treatment of abdominal pain syndrome and the rational usage of laxatives in constipation in children is shown.Key words: children, irritable bowel syndrome, diagnostics, treatment.

  1. Gut microbiome and its role in cardiovascular diseases.

    Science.gov (United States)

    Ahmadmehrabi, Shadi; Tang, W H Wilson

    2017-11-01

    In recent years, an interest in intestinal microbiota-host interactions has increased due to many findings about the impact of gut bacteria on human health and disease. Dysbiosis, a change in the composition of the gut microbiota, has been associated with much pathology, including cardiovascular diseases (CVD). This article will review normal functions of the gut microbiome, its link to CVD, and potential therapeutic interventions. The recently discovered contribution of gut microbiota-derived molecules in the development of heart disease and its risk factors has significantly increased attention towards the connection between our gut and heart. The gut microbiome is virtually an endocrine organ, arguably the largest, capable of contributing to and reacting to circulating signaling molecules within the host. Gut microbiota-host interactions occur through many pathways, including trimethylamine-N-oxide and short-chain fatty acids. These molecules and others have been linked to much pathology including chronic kidney disease, atherosclerosis, and hypertension. Although our understanding of gut microbiota-host interactions has increased recently; many questions remain about the mechanistic links between the gut microbiome and CVD. With further research, we may one day be able to add gut microbiota profiles as an assessable risk factor for CVD and target therapies towards the gut microbiota.

  2. Newborn Irritability Moderates the Association between Infant Attachment Security and Toddler Exploration and Sociability

    Science.gov (United States)

    Stupica, Brandi; Sherman, Laura J.; Cassidy, Jude

    2011-01-01

    This longitudinal investigation of 84 infants examined whether the effect of 12-month attachment on 18- and 24-month exploration and sociability with unfamiliar adults varied as a function of newborn irritability. As expected, results revealed an interaction between attachment (secure vs. insecure) and irritability (highly irritable vs. moderately…

  3. Testing GUTs: where do monopoles fit

    International Nuclear Information System (INIS)

    Ellis, J.

    1982-10-01

    The report shows why the inadequacies of the standard model of elementary particles impel some theorists toward embedding the strong, weak and electromagnetic interactions in a simple GUT group, and explains why the grand unification scale and hence the GUM (Grand Unified Monopoles) mass are expected to be so large (greater than or equal to 10 14 GeV). It goes on to describe some model GUTs, notably minimal SU(5) and supersymmetric (susy) GUTs. The grand unified analogues of generalized Cabibbo mixing angles are introduced relevant to the prediction of baryon decay modes in different theories as well as to the Decay modes catalyzed by GUMs. Phenomenologies of conventional and susy GUTs are contrasted including the potential increase in the grand unification scale as well as possible different baryon decay modes in susy GUTs. The phenomenology of GUMs is discussed, principally their ability to catalyze baryon decays. Some of the astrophysical and cosmological constraints on GUMs, GUMs, which make it difficult to imagine ever seeing a GUM and may impose serious restrictions on GUT model-building via their behavior in the very early universe are introduced. Finally, the reasons why GUMs are crucial aspects and tests of GUTs are summarized

  4. 33 CFR 117.537 - Townsend Gut.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Townsend Gut. 117.537 Section 117... OPERATION REGULATIONS Specific Requirements Maine § 117.537 Townsend Gut. The draw of the Southport (SR27) Bridge, at mile 0.7, across Townsend Gut between Boothbay Harbor and Southport, Maine shall open on...

  5. Attenuated nicotine‐like effects of varenicline but not other nicotinic ACh receptor agonists in monkeys receiving nicotine daily

    Science.gov (United States)

    Cunningham, Colin S; Moerke, Megan J; Javors, Martin A; Carroll, F Ivy

    2016-01-01

    Background and Purpose Chronic treatment can differentially impact the effects of pharmacologically related drugs that differ in receptor selectivity and efficacy. Experimental Approach The impact of daily nicotine treatment on the effects of nicotinic ACh receptor (nAChR) agonists was examined in two groups of rhesus monkeys discriminating nicotine (1.78 mg·kg−1 base weight) from saline. One group received additional nicotine treatment post‐session (1.78 mg·kg−1 administered five times daily, each dose 2 h apart; i.e. Daily group), and the second group did not (Intermittent group). Key Results Daily repeated nicotine treatment produced a time‐related increase in saliva cotinine. There was no significant difference in the ED50 values of the nicotine discriminative stimulus between the Daily and Intermittent group. Mecamylamine antagonized the effects of nicotine, whereas dihydro‐β‐erythroidine did not. Midazolam produced 0% nicotine‐lever responding. The nAChR agonists epibatidine, RTI‐36, cytisine and varenicline produced >96% nicotine‐lever responding in the Intermittent group. The respective maximum effects in the Daily group were 100, 72, 59 and 28%, which shows that the ability of varenicline to produce nicotine‐like responding was selectively decreased in the Daily as compared with the Intermittent group. When combined with nicotine, both varenicline and cytisine increased the potency of nicotine to produce discriminative stimulus effects. Conclusion and Implications Nicotine treatment has a greater impact on the sensitivity to the effects of varenicline as compared with some other nAChR agonists. Collectively, these results strongly suggest that varenicline differs from nicotine in its selectivity for multiple nAChR subtypes. PMID:27667659

  6. nAChR dysfunction as a common substrate for schizophrenia and comorbid nicotine addiction: current trends and perspectives

    Science.gov (United States)

    Parikh, Vinay; Kutlu, Munir Gunes; Gould, Thomas J.

    2016-01-01

    Introduction The prevalence of tobacco use in the population with schizophrenia is enormously high. Moreover, nicotine dependence is found to be associated with symptom severity and poor outcome in patients with schizophrenia. The neurobiological mechanisms that explain schizophrenia-nicotine dependence comorbidity are not known. This study systematically reviews the evidence highlighting the contribution of nicotinic acetylcholine receptors (nAChRs) to nicotine abuse in schizophrenia. Methods Electronic data bases (Medline, Google Scholar, and Web of Science) were searched using the selected key words that match the aims set forth for this review. A total of 275 articles were used for the qualitative synthesis of this review. Results Substantial evidence from preclinical and clinical studies indicated that dysregulation of α7 and β2-subunit containing nAChRs account for the cognitive and affective symptoms of schizophrenia and nicotine use may represent a strategy to remediate these symptoms. Additionally, recent meta-analyses proposed that early tobacco use may itself increase the risk of developing schizophrenia. Genetic studies demonstrating that nAChR dysfunction that may act as a shared vulnerability factor for comorbid tobacco dependence and schizophrenia were found to support this view. The development of nAChR modulators was considered an effective therapeutic strategy to ameliorate psychiatric symptoms and to promote smoking cessation in schizophrenia patients. Conclusions The relationship between schizophrenia and smoking is complex. While the debate for the self-medication versus addiction vulnerability hypothesis continues, it is widely accepted that a dysfunction in the central nAChRs represent a common substrate for various symptoms of schizophrenia and comorbid nicotine dependence. PMID:26803692

  7. Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment.

    Science.gov (United States)

    Dobrijevic, Dragana; Abraham, Anne-Laure; Jamet, Alexandre; Maguin, Emmanuelle; van de Guchte, Maarten

    2016-01-01

    The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. The gut microbiota is shaped by millennia of evolution to co-exist with the host in commensal or symbiotic relationships. Members of the gut microbiota perform specific molecular functions important in the human gut environment. This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. We identified several functions that are overrepresented in the human gut bacteria which had not been recognized in a global approach. The observed under-representation of certain other functions may be equally important for gut homeostasis. Together, these analyses provide us with new information about this environment so critical to our health and well-being.

  8. Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment.

    Directory of Open Access Journals (Sweden)

    Dragana Dobrijevic

    Full Text Available The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. The gut microbiota is shaped by millennia of evolution to co-exist with the host in commensal or symbiotic relationships. Members of the gut microbiota perform specific molecular functions important in the human gut environment. This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. We identified several functions that are overrepresented in the human gut bacteria which had not been recognized in a global approach. The observed under-representation of certain other functions may be equally important for gut homeostasis. Together, these analyses provide us with new information about this environment so critical to our health and well-being.

  9. Effects of acetylcholine (ACh) and norepinephrine (NE) on phosphatidylinositol 4,5-bisphosphate (PIP2) turnover in rabbit cornea

    International Nuclear Information System (INIS)

    Akhtar, R.A.; Abdel-Latif, A.A.

    1986-01-01

    Muscarinic cholinergic and α 1 -adrenergic agonists provoke hydrolysis of PIP 2 into diacylglycerol (DG) and inositol trisphosphate (IP 3 ) in a wide variety of tissue. Recently, IP 3 has been shown to mobilize Ca 2+ from ER in several permeabilized tissue preparations. Although rabbit cornea is enriched in ACh and NE, the physiological function of these neurotransmitters is unclear. The present studies were initiated to determine the effects of cholinergic and adrenergic agonists on PIP 2 turnover in the cornea. Addition of ACh or NE (50 μM each) to the 32 P-labeled corneas for 10 min decreased the radioactivity in PIP 2 by 33 and 36%, and increased the radioactivity in phosphatidic acid by 72 and 52%, respectively. When the corneas were labeled with myo-[ 3 H]inositol, ACh and NE increased the accumulation of IP 3 by 92 and 48%, respectively. The effects of ACh and NE on phospholipid labeling and IP 3 accumulation were specifically inhibited by atropine (10 μM) and prazosin (10 μM), respectively. The data suggest the presence of muscarinic cholinergic and α 1 -adrenergic receptors in the rabbit cornea. Furthermore, activation of these receptors leads to cleavage of PIP 2 into DG and IP 3 which may function as second messengers in this tissue

  10. Non-Irritant Baby Shampoos May Cause Cataract Development

    Directory of Open Access Journals (Sweden)

    Omer Faruk Tekbas

    2008-02-01

    Full Text Available BACKGROUND: The effect of different shampoo formulations as a risk factor for cataract formation was investigated in Sprague Dawley rats in the present study. METHODS: Study was performed by using 20 rats. Two different shampoos used by adult subjects and two different baby shampoos were used in the study. Different shampoos were used in different groups for 14 days, and they were followed for changes. RESULTS: Different degree of opacities were observed in 4 (40%, 4 (40%, 5 (50%, and 6 (60% eyes in Groups A, B, C, and D, respectively. There was no statistically significant difference for formation of cataract between the groups (p>0.05. The number of irritated eyes was significantly lower (p<0.05 in groups C (10% and D (20% compared to groups A (90% and B (80%. CONCLUSION: The use of non-irritant baby shampoos does not seem to eliminate the risk of cataract formation and these should even be used more carefully as the non-irritant shampoo will have more contact with the eye. [TAF Prev Med Bull. 2008; 7(1: 1-6

  11. Nerve growth factor and diarrhea-predominant irritable bowel syndrome (IBS-D): a potential therapeutic target?

    Science.gov (United States)

    Xu, Xiao-juan; Liu, Liang; Yao, Shu-kun

    2016-01-01

    Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by recurrent abdominal pain or discomfort associated with abnormal bowel habits. Diarrhea-predominant IBS (IBS-D) is a major subtype of IBS, the predominant manifestations of which are abdominal pain and diarrhea. The pathogenesis of IBS-D remained unknown until recently. The effects of psychosocial stress, central hypervigilance, neuroendocrine abnormality, disturbed gastrointestinal motility, mucosal immune activation, intestinal barrier dysfunction, visceral hypersensitivity (VH), altered gut flora, and genetic susceptibility may be involved in its development. Recently, increased attention has been placed on the neural-immune-endocrine network mechanism in IBS-D, especially the role of various neuroendocrine mediators. As a member of the neurotrophin family, nerve growth factor (NGF) has diverse biological effects, and participates in the pathogenesis of many diseases. Basic studies have demonstrated that NGF is associated with inflammatory- and stress-related VH, as well as stress-related intestinal barrier dysfunction. The aim of this study is to summarize recent literature and discuss the role of NGF in the pathophysiology of IBS-D, especially in VH and intestinal barrier dysfunction, as well as its potential as a therapeutic target in IBS-D.

  12. Eye Irritation Test of Bovis Calculus Pharmacopuncture Solutions for Eye Drop

    Directory of Open Access Journals (Sweden)

    Hyeong-sik Seo

    2008-06-01

    Full Text Available Objective : This study was done to investigate the safety of Bovis Calculus pharmacopuncture solution manufactured with freezing dryness method to use eye drop. Methods : The eye irritation test of this material was performed according to the Regulation of Korea Food & Drug Administration (2005. 10. 21, KFDA 2005-60. After Bovis Calculus pharmacopuncture solution was medicated in the left eye of the rabbits, the auther observed eye irritation of the cornea, iris, conjunctiva at 1, 2, 3, 4 & 7day. Results : 1. After Bovis Calculus pharmacopuncture solution was medicated in the left eye of the rabbits, there wasn’t physical problem at 9 rabbits. 2. After Bovis Calculus pharmacopuncture solutionwas medicated in the left eye of the rabbits, there wasn’t eye irritation of the cornea, iris, conjunctiva at 1, 2, 3, 4 & 7day. Conclusions : I suggested that Bovis Calculus pharmacopuncture solution didn’t induced eye irritation in rabbits.

  13. How gut transcriptional function of Drosophila melanogaster varies with the presence and composition of the gut microbiota.

    Science.gov (United States)

    Bost, Alyssa; Franzenburg, Soeren; Adair, Karen L; Martinson, Vincent G; Loeb, Greg; Douglas, Angela E

    2018-04-01

    Despite evidence from laboratory experiments that perturbation of the gut microbiota affects many traits of the animal host, our understanding of the effect of variation in microbiota composition on animals in natural populations is very limited. The core purpose of this study on the fruit fly Drosophila melanogaster was to identify the impact of natural variation in the taxonomic composition of gut bacterial communities on host traits, with the gut transcriptome as a molecular index of microbiota-responsive host traits. Use of the gut transcriptome was validated by demonstrating significant transcriptional differences between the guts of laboratory flies colonized with bacteria and maintained under axenic conditions. Wild Drosophila from six field collections made over two years had gut bacterial communities of diverse composition, dominated to varying extents by Acetobacteraceae and Enterobacteriaceae. The gut transcriptomes also varied among collections and differed markedly from those of laboratory flies. However, no overall relationship between variation in the wild fly transcriptome and taxonomic composition of the gut microbiota was evident at all taxonomic scales of bacteria tested for both individual fly genes and functional categories in Gene Ontology. We conclude that the interaction between microbiota composition and host functional traits may be confounded by uncontrolled variation in both ecological circumstance and host traits (e.g., genotype, age physiological condition) under natural conditions, and that microbiota effects on host traits identified in the laboratory should, therefore, be extrapolated to field population with great caution. © 2017 John Wiley & Sons Ltd.

  14. Gut immunity in Lepidopteran insects.

    Science.gov (United States)

    Wu, Kai; Yang, Bing; Huang, Wuren; Dobens, Leonard; Song, Hongsheng; Ling, Erjun

    2016-11-01

    Lepidopteran insects constitute one of the largest fractions of animals on earth, but are considered pests in their relationship with man. Key to the success of this order of insects is its ability to digest food and absorb nutrition, which takes place in the midgut. Because environmental microorganisms can easily enter Lepidopteran guts during feeding, the innate immune response guards against pathogenic bacteria, virus and microsporidia that can be devoured with food. Gut immune responses are complicated by both resident gut microbiota and the surrounding peritrophic membrane and are distinct from immune responses in the body cavity, which depend on the function of the fat body and hemocytes. Due to their relevance to agricultural production, studies of Lepidopteran insect midgut and immunity are receiving more attention, and here we summarize gut structures and functions, and discuss how these confer immunity against different microorganisms. It is expected that increased knowledge of Lepidopteran gut immunity may be utilized for pest biological control in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Transcutaneous sacral neurostimulation for irritative voiding dysfunction.

    Science.gov (United States)

    Walsh, I K; Johnston, R S; Keane, P F

    1999-01-01

    Patients with irritative voiding dysfunction are often unresponsive to standard clinical treatment. We evaluated the response of such individuals to transcutaneous electrical stimulation of the third sacral nerve. 32 patients with refractory irritative voiding dysfunction (31 female and 1 male; mean age 47 years) were recruited to the study. Ambulatory transcutaneous electrical neurostimulation was applied bilaterally to the third sacral dermatomes for 1 week. Symptoms of frequency, nocturia, urgency, and bladder pain were scored by each patient throughout and up to 6 months following treatment. The mean daytime frequency was reduced from 11.3 to 7.96 (p = 0.01). Nocturia episodes were reduced from a mean of 2.6 to 1.8 (p = 0.01). Urgency and bladder pain mean symptom scores were reduced from 5.97 to 4.89 and from 1.48 to 0.64, respectively. After stopping therapy, symptoms returned to pretreatment levels within 2 weeks in 40% of the patients and within 6 months in 100%. Three patients who continued with neurostimulation remained satisfied with this treatment modality at 6 months. Transcutaneous third sacral nerve stimulation may be an effective and noninvasive ambulatory technique for the treatment of patients with refractory irritative voiding dysfunction. Following an initial response, patients may successfully apply this treatment themselves to ensure long-term relief.

  16. Applicability of an exaggerated forearm wash test for efficacy testing of two corticosteroids, tacrolimus and glycerol, in topical formulations against skin irritation induced by two different irritants

    DEFF Research Database (Denmark)

    Clemmensen, A; Andersen, F; Petersen, T K

    2011-01-01

    applied, we tested the efficacy of four anti-irritant compounds using the two different irritants sodium lauryl sulfate (SLS) and nonanoic acid (NON). Methods: In a randomized, double-blind, controlled trial, healthy volunteers were exposed to 5% SLS and 50% NON (the right and the left forearm...

  17. Fetal cholinergic anti-inflammatory pathway and necrotizing enterocolitis: the brain-gut connection begins in utero

    Directory of Open Access Journals (Sweden)

    Luca eGarzoni

    2013-08-01

    Full Text Available Necrotizing enterocolitis (NEC is an acute neonatal inflammatory disease that affects the intestine and may result in necrosis, systemic sepsis and multisystem organ failure. NEC affects 5-10% of all infants with birth weight ≤ 1500 g or gestational age less than 30 weeks. Chorioamnionitis (CA is the main manifestation of pathological inflammation in the fetus and is strongly associated with NEC. CA affects 20% of full-term pregnancies and up to 60% of preterm pregnancies and, notably, is often an occult finding. Intrauterine exposure to inflammatory stimuli may switch innate immunity cells such as macrophages to a reactive phenotype (‘priming’. Confronted with renewed inflammatory stimuli during labour or postnatally, such sensitized cells can sustain a chronic or exaggerated production of proinflammatory cytokines associated with NEC (two-hit hypothesis. Via the cholinergic anti-inflammatory pathway, a neurally mediated innate anti-inflammatory mechanism, higher levels of vagal activity are associated with lower systemic levels of proinflammatory cytokines. This effect is mediated by the α7 subunit nicotinic acetylcholine receptor (α7nAChR on macrophages. The gut is the most extensive organ innervated by the vagus nerve; it is also the primary site of innate immunity in the newborn. Here we review the mechanisms of possible neuroimmunological brain-gut interactions involved in the induction and control of antenatal intestinal inflammatory response and priming. We propose a neuroimmunological framework to 1 study the long-term effects of perinatal intestinal response to infection and 2 to uncover new targets for preventive and therapeutic intervention.

  18. Pediatric Mania: The Controversy between Euphoria and Irritability

    Science.gov (United States)

    Serra, Giulia; Uchida, Mai; Battaglia, Claudia; Casini, Maria Pia; De Chiara, Lavinia; Biederman, Joseph; Vicari, Stefano; Wozniak, Janet

    2017-01-01

    Abstract: Pediatric Bipolar Disorder (BD) is a highly morbid pediatric psychiatric disease, consistently associated with family psychiatric history of mood disorders and associated with high levels of morbidity and disability and with a great risk of suicide. While there is a general consensus on the symptomatology of depression in childhood, the phenomenology of pediatric mania is still highly debated and the course and long-term outcome of pediatric BD still need to be clarified. We reviewed the available studies on the phenomenology of pediatric mania with the aim of summarizing the prevalence, demographics, clinical correlates and course of these two types of pediatric mania. Eighteen studies reported the number of subjects presenting with either irritable or elated mood during mania. Irritability has been reported to be the most frequent clinical feature of pediatric mania reaching a sensitivity of 95–100% in several samples. Only half the studies reviewed reported on number of episodes or cycling patterns and the described course was mostly chronic and ultra-rapid whereas the classical episodic presentation was less common. Few long-term outcome studies have reported a diagnostic stability of mania from childhood to young adult age. Future research should focus on the heterogeneity of irritability aiming at differentiating distinct subtypes of pediatric psychiatric disorders with distinct phenomenology, course, outcome and biomarkers. Longitudinal studies of samples attending to mood presentation, irritable versus elated, and course, chronic versus episodic, may help clarify whether these are meaningful distinctions in the course, treatment and outcome of pediatric onset bipolar disorder. PMID:28503110

  19. Pediatric Mania: The Controversy between Euphoria and Irritability.

    Science.gov (United States)

    Serra, Giulia; Uchida, Mai; Battaglia, Claudia; Casini, Maria Pia; De Chiara, Lavinia; Biederman, Joseph; Vicari, Stefano; Wozniak, Janet

    2017-04-01

    Pediatric Bipolar Disorder (BD) is a highly morbid pediatric psychiatric disease, consistently associated with family psychiatric history of mood disorders and associated with high levels of morbidity and disability and with a great risk of suicide. While there is a general consensus on the symptomatology of depression in childhood, the phenomenology of pediatric mania is still highly debated and the course and long-term outcome of pediatric BD still need to be clarified. We reviewed the available studies on the phenomenology of pediatric mania with the aim of summarizing the prevalence, demographics, clinical correlates and course of these two types of pediatric mania. Eighteen studies reported the number of subjects presenting with either irritable or elated mood during mania. Irritability has been reported to be the most frequent clinical feature of pediatric mania reaching a sensitivity of 95-100% in several samples. Only half the studies reviewed reported on number of episodes or cycling patterns and the described course was mostly chronic and ultra-rapid whereas the classical episodic presentation was less common. Few long-term outcome studies have reported a diagnostic stability of mania from childhood to young adult age. Future research should focus on the heterogeneity of irritability aiming at differentiating distinct subtypes of pediatric psychiatric disorders with distinct phenomenology, course, outcome and biomarkers. Longitudinal studies of samples attending to mood presentation, irritable versus elated, and course, chronic versus episodic, may help clarify whether these are meaningful distinctions in the course, treatment and outcome of pediatric onset bipolar disorder.

  20. Brain Gut Microbiome Interactions and Functional Bowel Disorders

    Science.gov (United States)

    Mayer, Emeran A.; Savidge, Tor; Shulman, Robert J.

    2014-01-01

    Alterations in the bidirectional interactions between the gut and the nervous system play an important role in IBS pathophysiology and symptom generation. A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. Characterizations of alterations of gut microbiota in unselected IBS patients, and assessment of changes in subjective symptoms associated with manipulations of the gut microbiota with prebiotics, probiotics and antibiotics support a small, but poorly defined role of dybiosis in overall IBS symptoms. It remains to be determined if the observed abnormalities are a consequence of altered top down signaling from the brain to the gut and microbiota, if they are secondary to a primary perturbation of the microbiota, and if they play a role in the development of altered brain gut interactions early in life. Different mechanisms may play role in subsets of patients. Characterization of gut microbiome alterations in large cohorts of well phenotyped patients as well as evidence correlating gut metabolites with specific abnormalities in the gut brain axis are required to answer these questions. PMID:24583088

  1. Benzalkonium chloride neutralizes the irritant effect of sodium dodecyl sulfate.

    Science.gov (United States)

    McFadden, J P; Holloway, D B; Whittle, E G; Basketter, D A

    2000-11-01

    When benzalkonium chloride (BKC), a cationic surfactant, is added to sodium dodecyl sulfate (SDS), an anionic surfactant, and used in patch testing, on the basis of their known physicochemical interaction, it is possible to predict that there will be a tendency towards a reduction in the expected irritant response when compared to SDS alone. The aim of this study was to investigate whether BKC could reduce the irritant response to SDS when applied after the SDS exposure. 54 non-atopic adult volunteers were recruited for the study. 20% SDS was applied for 2 h under occlusion. 1% BKC was then applied to the same site. Various controls, including SDS application followed by water for 2 h, were included. The irritant reaction was assessed at 24 h and 48 h. 40 of the 54 subjects had some reaction when SDS was applied for 2 h followed by either benzalkonium chloride or water control under occlusion. In comparison to water control, where BKC was applied after SDS, 20 of the 40 responders had a weaker reaction but only 4 had a stronger response. This study shows that BKC applied to skin exposed to SDS attenuates the resulting irritant reaction.

  2. Gut transit is associated with gastrointestinal symptoms and gut hormone profile in patients with cirrhosis

    DEFF Research Database (Denmark)

    Kalaitzakis, Evangelos; Sadik, Riadh; Holst, Jens Juul

    2008-01-01

    BACKGROUND & AIMS: Liver cirrhosis is associated with increased prevalence of gastrointestinal symptoms, insulin resistance, and altered gut transit. We aimed to assess the prevalence of gut transit abnormalities in patients with cirrhosis, compared with healthy controls, and to evaluate the rela......BACKGROUND & AIMS: Liver cirrhosis is associated with increased prevalence of gastrointestinal symptoms, insulin resistance, and altered gut transit. We aimed to assess the prevalence of gut transit abnormalities in patients with cirrhosis, compared with healthy controls, and to evaluate...... the relation of gut transit with gastrointestinal symptoms and postprandial glucose and hormone profiles. METHODS: Half gastric emptying, small bowel residence, and colonic filling times were measured with a validated radiologic procedure in 42 consecutive patients with cirrhosis. In a subgroup of 25 patients......, gastrointestinal symptoms were evaluated by using a validated questionnaire and a caloric satiation test. Postprandial glucose, insulin, leptin, ghrelin, glucagon-like peptide 1, and PYY responses were also studied. Eighty-three healthy subjects served as controls for the transit studies and 10 for the hormone...

  3. Linking the Gut Microbial Ecosystem with the Environment: Does Gut Health Depend on Where We Live?

    Directory of Open Access Journals (Sweden)

    Nishat Tasnim

    2017-10-01

    Full Text Available Global comparisons reveal a decrease in gut microbiota diversity attributed to Western diets, lifestyle practices such as caesarian section, antibiotic use and formula-feeding of infants, and sanitation of the living environment. While gut microbial diversity is decreasing, the prevalence of chronic inflammatory diseases such as inflammatory bowel disease, diabetes, obesity, allergies and asthma is on the rise in Westernized societies. Since the immune system development is influenced by microbial components, early microbial colonization may be a key factor in determining disease susceptibility patterns later in life. Evidence indicates that the gut microbiota is vertically transmitted from the mother and this affects offspring immunity. However, the role of the external environment in gut microbiome and immune development is poorly understood. Studies show that growing up in microbe-rich environments, such as traditional farms, can have protective health effects on children. These health-effects may be ablated due to changes in the human lifestyle, diet, living environment and environmental biodiversity as a result of urbanization. Importantly, if early-life exposure to environmental microbes increases gut microbiota diversity by influencing patterns of gut microbial assembly, then soil biodiversity loss due to land-use changes such as urbanization could be a public health threat. Here, we summarize key questions in environmental health research and discuss some of the challenges that have hindered progress toward a better understanding of the role of the environment on gut microbiome development.

  4. Impact of irritability: a 2-year observational study of outpatients with bipolar I or schizoaffective disorder.

    Science.gov (United States)

    Berk, Lesley; Hallam, Karen T; Venugopal, Kamalesh; Lewis, Andrew James; Austin, David W; Kulkarni, Jayashri; Dodd, Seetal; de Castella, Anthony; Fitzgerald, Paul B; Berk, Michael

    2017-05-01

    Many people experience irritability when manic, hypomanic, or depressed, yet its impact on illness severity and quality of life in bipolar and schizoaffective disorders is poorly understood. This study aimed to examine the relationship between irritability and symptom burden, functioning, quality of life, social support, suicidality, and overall illness severity in a naturalistic cohort of people with bipolar I or schizoaffective disorder. We used data from 239 adult outpatients with bipolar I or schizoaffective disorder in the Bipolar Comprehensive Outcomes Study (BCOS) - a non-interventional observational study with a 2-year follow-up period. Baseline demographic and clinical characteristics of participants with and without irritability were compared. A mixed-model repeated measures analysis was conducted to examine the longitudinal effect of irritability on clinical and quality-of-life variables over follow-up using significant baseline variables. At baseline, 54% of participants were irritable. Baseline irritability was associated with illness severity, mania, depression, psychotic symptoms, suicidality, poor functioning, and quality of life, but not diagnosis (schizoaffective/bipolar disorder). Participants with irritability were less likely to have a partner and perceived less adequate social support. On average, over follow-up, those with irritability reported more symptoms, functional impairment, and suicidality. Furthermore, the effects of irritability could not be fully explained by illness severity. Irritability was associated with more negative symptomatic, functional, and quality-of-life outcomes and suicidality. The identification, monitoring, and targeted treatment of irritability may be worth considering, to enhance health and wellbeing outcomes for adults with bipolar and schizoaffective disorders. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Kiwifruit, mucins, and the gut barrier.

    Science.gov (United States)

    Moughan, Paul J; Rutherfurd, Shane M; Balan, Prabhu

    2013-01-01

    Kiwifruit has long been regarded in China, where it originated from, for its health properties and particularly in relation to digestion and general gut health. There are a number of physical and chemical properties of the fruit, including its dietary fiber content, the presence of raphides, its high water holding capacity and actinidin content, that suggest that kiwifruit may be effective in influencing gut mucin production and thus enhancing the integrity of the gut barrier. The mucous layer, which comprises mucins and other materials, overlying the mucosal epithelium, is an important component of the gut barrier. The gut barrier plays a crucial role in separating the host from the often noxious external environment. The mucous layer, which covers the entire gastrointestinal tract (GIT), is the front line of innate host defense. There have been few direct studies of the effect of kiwifruit ingestion on mucin production in the GIT, and findings that are available using animal models are somewhat inconsistent. Taking results for digesta mucin content, number of goblet cells, and mucin gene expression, together, it would seem that green kiwifruit and possibly gold kiwifruit do influence gut mucin production, and the kiwifruit as part of a balanced diet may help to maintain the mucous layer and gut barrier. More corroborative experimental evidence is needed, and studies need to be undertaken in humans. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Gut microbiota and malnutrition.

    Science.gov (United States)

    Million, Matthieu; Diallo, Aldiouma; Raoult, Didier

    2017-05-01

    Malnutrition is the leading cause of death worldwide in children under the age of five, and is the focus of the first World Health Organization (WHO) Millennium Development Goal. Breastfeeding, food and water security are major protective factors against malnutrition and critical factors in the maturation of healthy gut microbiota, characterized by a transient bifidobacterial bloom before a global rise in anaerobes. Early depletion in gut Bifidobacterium longum, a typical maternal probiotic, known to inhibit pathogens, represents the first step in gut microbiota alteration associated with severe acute malnutrition (SAM). Later, the absence of the Healthy Mature Anaerobic Gut Microbiota (HMAGM) leads to deficient energy harvest, vitamin biosynthesis and immune protection, and is associated with diarrhea, malabsorption and systemic invasion by microbial pathogens. A therapeutic diet and infection treatment may be unable to restore bifidobacteria and HMAGM. Besides refeeding and antibiotics, future trials including non-toxic missing microbes and nutrients necessary to restore bifidobacteria and HMAGM, including prebiotics and antioxidants, are warranted in children with severe or refractory disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. CON4EI: SkinEthic™ Human Corneal Epithelium Eye Irritation Test (SkinEthic™ HCE EIT) for hazard identification and labelling of eye irritating chemicals.

    Science.gov (United States)

    Van Rompay, A R; Alépée, N; Nardelli, L; Hollanders, K; Leblanc, V; Drzewiecka, A; Gruszka, K; Guest, R; Kandarova, H; Willoughby, J A; Verstraelen, S; Adriaens, E

    2018-06-01

    Assessment of ocular irritancy is an international regulatory requirement and a necessary step in the safety evaluation of industrial and consumer products. Although a number of in vitro ocular irritation assays exist, none are capable of fully categorizing chemicals as a stand-alone assay. Therefore, the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project was developed with the goal of assessing the reliability of eight in vitro/alternative test methods as well as establishing an optimal tiered-testing strategy. One of the in vitro assays selected was the validated SkinEthic™ Human Corneal Epithelium Eye Irritation Test method (SkinEthic™ HCE EIT). The SkinEthic™ HCE EIT has already demonstrated its capacity to correctly identify chemicals (both substances and mixtures) not requiring classification and labelling for eye irritation or serious eye damage (No Category). The goal of this study was to evaluate the performance of the SkinEthic™ HCE EIT test method in terms of the important in vivo drivers of classification. For the performance with respect to the drivers all in vivo Cat 1 and No Cat chemicals were 100% correctly identified. For Cat 2 chemicals the liquids and the solids had a sensitivity of 100% and 85.7%, respectively. For the SkinEthic™ HCE EIT test method, 100% concordance in predictions (No Cat versus No prediction can be made) between the two participating laboratories was obtained. The accuracy of the SkinEthic™ HCE EIT was 97.5% with 100% sensitivity and 96.9% specificity. The SkinEthic™ HCE EIT confirms its excellent results of the validation studies. Copyright © 2017. Published by Elsevier Ltd.

  8. Does Your Patient’s Urine Turns Dark? Alkaptonuria and Low Back Ache: A Literature Review

    Science.gov (United States)

    Kanniyan, Kalaivanan; Pathak, Aditya C; Dhammi, Ish Kumar; Jain, Anil Kumar

    2014-01-01

    Introduction: Alkaptonuria is a very rare inborn error of amino acid metabolism due to deficient homogentisic acid (HGA) oxidase enzyme leading to accumulation of HGA in plasma, cartilage, other tissues of human body and its excretion in urine. It has both systemic and peripheral signs and symptoms. Though low back is a common symptom of alkaptonuria but, in the absence of ochronosis it is rare. Alkaptonuria itself is very rare occurrence with no specific treatment option available to reverse the effect as yet. Case Report: A 38-year-old male, embroidery worker presented with chronic low back ache with history of staining of clothes in infancy. Later on laboratory and the radiological investigation patient was diagnosed to have alkaptonuria without ochronosis. No other systemic manifestation was present. Patient was treated conservatively and responded well. Conclusion: Though alkaptonuria is a very rare disease, and the occurrence of low back-ache in absence of ochronosis is much rarer. One must be aware of this inborn error of metabolism. Early diagnosis though being “diagnosis of exclusion” for low back-ache, high index of suspicion is advantageous as symptomatic treatment of the alkaptonuria can be initiated and evaluation of other systemic organs can be done in early stages itself. PMID:27298997

  9. Eye irritancy screening for classification of chemicals.

    Science.gov (United States)

    van Erp, Y H; Weterings, P J

    1990-01-01

    A screening method was applied to determine the eye irritation potential of industrial chemicals. Bovine eyes (BE) were used to predict corneal damage and chicken egg chorioallantoic membranes (CAM) to estimate the irritancy potential of chemical substances towards the conjunctivae. Exposure of the BE to a test substance is followed by grading of the corneal opacity and epithelial injury. The CAM is inspected for signs of capillary injection, haemorrhages and coagulation. The tests are collectively called the BECAM assay. So far, almost 150 substances have been evaluated in this test system. A good correlation was observed between the BECAM assay and in vivo data; less than 5% of chemicals showed a clear disagreement. Also the assay is promising for labelling requirements according to the EEC criteria.

  10. Precision LEP data, supersymmetric GUTs and string unification

    International Nuclear Information System (INIS)

    Ellis, J.; Kelley, S.; Nanopoulos, D.V.; Houston Area Research Center

    1990-01-01

    The precision of sin 2 θ w MS (m Z ) extracted from LEP data (0.233±0.001) confirms the prediction of minimal supersymmetric GUTs (0.235±0.004) within the errors of about 2%. Moreover, supersymmetric GUTs with three generations and a heavy top quark also predict m b =5.2±0.3 GeV in perfect agreement with potential model estimates (5.0±0.2 GeV). String unification would require that the effective grand unification scale m GUT be no larger than the effective string unification scale m SU , which is indeed consistent with the LEP data, which indicate m GUT ≅ 2x10 16 GeV in a minimal supersymmetric GUT, compared with the theoretical estimate m SU ≅ 10 17 GeV. Specific choices of the string model moduli could enforce m GUT =m SU even in minimal supersymmetric GUTs, whilst non-minimal supersymmetric GUTs can reconcile the successful predictions of sin 2 θ w with m GUT = m SU for generic values of the moduli, but tend to have m b too large. (orig.)

  11. Gut dysfunction in Parkinson's disease

    Science.gov (United States)

    Mukherjee, Adreesh; Biswas, Atanu; Das, Shyamal Kumar

    2016-01-01

    Early involvement of gut is observed in Parkinson’s disease (PD) and symptoms such as constipation may precede motor symptoms. α-Synuclein pathology is extensively evident in the gut and appears to follow a rostrocaudal gradient. The gut may act as the starting point of PD pathology with spread toward the central nervous system. This spread of the synuclein pathology raises the possibility of prion-like propagation in PD pathogenesis. Recently, the role of gut microbiota in PD pathogenesis has received attention and some phenotypic correlation has also been shown. The extensive involvement of the gut in PD even in its early stages has led to the evaluation of enteric α-synuclein as a possible biomarker of early PD. The clinical manifestations of gastrointestinal dysfunction in PD include malnutrition, oral and dental disorders, sialorrhea, dysphagia, gastroparesis, constipation, and defecatory dysfunction. These conditions are quite distressing for the patients and require relevant investigations and adequate management. Treatment usually involves both pharmacological and non-pharmacological measures. One important aspect of gut dysfunction is its contribution to the clinical fluctuations in PD. Dysphagia and gastroparesis lead to inadequate absorption of oral anti-PD medications. These lead to response fluctuations, particularly delayed-on and no-on, and there is significant relationship between levodopa pharmacokinetics and gastric emptying in patients with PD. Therefore, in such cases, alternative routes of administration or drug delivery systems may be required. PMID:27433087

  12. Long-term repetitive sodium lauryl sulfate-induced irritation of the skin: an in vivo study.

    Science.gov (United States)

    Branco, Nara; Lee, Ivy; Zhai, Hongbo; Maibach, Howard I

    2005-11-01

    Skin may adapt to topical irritants through accommodation. This study focuses on long-term exposure to irritants and attempts to demonstrate accommodation. Sodium lauryl sulfate (SLS) induced irritant contact dermatitis at 3 concentrations (0.025% to 0.075%). Distilled water, acetone and an empty chamber served as controls. Experimental compounds were applied to forearms of 7 healthy volunteers for 24 hr before replacing by a fresh chamber for 6 non-consecutive weeks over 103 days. Possible accommodation was quantified by visual scoring (erythema and dryness) and by bioengineering parameters: transepidermal water loss (TEWL), capacitance, chromametry and laser Doppler flowmetry (LDF). Significant erythema, dryness, elevated TEWL, skin colour reflectance and LDF values occurred during the exposure periods. Upon repeat exposure, an immediate and augmented response in erythema, TEWL, skin colour reflectance and LDF developed. However, irritant skin changes were not sustained. Irritation parameters return to baseline after cessation of exposure. There was no evidence of sustained irritation or accommodation after the last exposure. Study findings do not document sustained accommodation or adaptive hyposensitivity after long-term repetitive irritant exposure under these test conditions. Alternative models should be developed to prove or disprove the accommodation hypothesis.

  13. First Foods and Gut Microbes

    DEFF Research Database (Denmark)

    Laursen, Martin Frederik; Bahl, Martin Iain; Michaelsen, Kim F.

    2017-01-01

    The establishment of the human gut microbiota in early life has been associated with later health and disease. During the 1st months after birth, the microbial composition in the gut is known to be affected by the mode of delivery, use of antibiotics, geographical location and type of feeding...... of this window is currently debated, but it likely coincides with the complementary feeding period, marking the gradual transition from milk- based infant feeding to family diet usually occurring between 6 and 24 months. Furthermore, the 'first 1000 days,' i.e., the period from conception until age 2 years...... microbiota development. This perspective paper summarizes the currently very few studies addressing the effects of complementary diet on gut microbiota, and highlights the recent finding that transition to family foods greatly impacts the development of gut microbial diversity. Further, we discuss potential...

  14. The gut microbiota, obesity and insulin resistance

    Science.gov (United States)

    The human gut is densely populated by commensal and symbiotic microbes (the "gut microbiota"), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflam...

  15. Metagenomic Analysis of the Human Gut Microbiome

    DEFF Research Database (Denmark)

    dos Santos, Marcelo Bertalan Quintanilha

    Understanding the link between the human gut microbiome and human health is one of the biggest scientific challenges in our decade. Because 90% of our cells are bacteria, and the microbial genome contains 200 times more genes than the human genome, the study of the human microbiome has...... the potential to impact many areas of our health. This PhD thesis is the first study to generate a large amount of experimental data on the DNA and RNA of the human gut microbiome. This was made possible by our development of a human gut microbiome array capable of profiling any human gut microbiome. Analysis...... of our results changes the way we link the gut microbiome with diseases. Our results indicate that inflammatory diseases will affect the ecological system of the human gut microbiome, reducing its diversity. Classification analysis of healthy and unhealthy individuals demonstrates that unhealthy...

  16. Differentiating coeliac disease from irritable bowel syndrome by urinary volatile organic compound analysis--a pilot study.

    Directory of Open Access Journals (Sweden)

    Ramesh P Arasaradnam

    Full Text Available Coeliac disease (CD, a T-cell-mediated gluten sensitive enteropathy, affects ∼ 1% of the UK population and can present with wide ranging clinical features, often being mistaken for Irritable Bowel Syndrome (IBS. Heightened clinical awareness and serological screening identifies those with potential coeliac disease; the diagnosis is confirmed with duodenal biopsies, and symptom improvement with a gluten-free diet. Limitations to diagnosis are false negative serology and reluctance to undergo biopsy. The gut microbiome is altered in several gastrointestinal disorders, causing altered gut fermentation patterns recognisable by volatile organic compounds (VOC analysis in urine, breath and faeces. We aimed to determine if CD alters the urinary VOC pattern, distinguishing it from IBS. 47 patients were recruited, 27 with established CD, on gluten free diets, and 20 with diarrhoea-predominant IBS (D-IBS. Collected urine was stored frozen in 10 ml aliquots. For assay, the specimens were heated to 40 ± 0.1°C and the headspace analysed by Field Asymmetric Ion Mobility Spectrometry (FAIMS. Machine learning algorithms were used for statistical evaluation. Samples were also analysed using Gas chromatography and mass spectroscopy (GC-MS. Sparse logistic regression showed that FAIMS distinguishes VOCs in CD vs D-IBS with ROC curve AUC of 0.91 (0.83-0.99, sensitivity and specificity of 85% respectively. GCMS showed a unique peak at 4'67 found only in CD, not D-IBS, which correlated with the compound 1,3,5,7 cyclooctatetraene. This study suggests that FAIMS offers a novel, non-invasive approach to identify those with possible CD, and distinguishes from D-IBS. It offers the potential for monitoring compliance with a gluten-free diet at home. The presence of cyclooctatetraene in CD specimens will need further validation.

  17. Limbic Irritability, Neuronal Complexity and Smoking

    Czech Academy of Sciences Publication Activity Database

    Svetlak, M.; Bob, P.; Černík, M.; Konečný, P.; Chládek, Jan; Svrček, M.; Kukleta, M.

    2008-01-01

    Roč. 50, č. 3 (2008), s. 85 ISSN 0001-7604. [International CIANS Conference 2008: Higher Brain Functions. 28.09.2008-02.10.2008, Smolenice] Institutional research plan: CEZ:AV0Z20650511 Keywords : smoking * limbic irritability * stress * complexity * EDA Subject RIV: FH - Neurology

  18. Irritable bowel syndrome and vocational stress: individual ...

    African Journals Online (AJOL)

    Irritable bowel syndrome and vocational stress: individual psychotherapy: research. ... The goal of this study was to provide individualised psychotherapy for a sample suffering from IBS and vocational stress. ... AJOL African Journals Online.

  19. Non-Irritant Baby Shampoos May Cause Cataract Development

    Directory of Open Access Journals (Sweden)

    Omer Faruk Tekbas

    2008-02-01

    Full Text Available BACKGROUND: The effect of different shampoo formulations as a risk factor for cataract formation was investigated in Sprague Dawley rats in the present study. METHODS: Study was performed by using 20 rats. Two different shampoos used by adult subjects and two different baby shampoos were used in the study. Different shampoos were used in different groups for 14 days, and they were followed for changes. RESULTS: Different degree of opacities were observed in 4 (40%, 4 (40%, 5 (50%, and 6 (60% eyes in Groups A, B, C, and D, respectively. There was no statistically significant difference for formation of cataract between the groups (p>0.05. The number of irritated eyes was significantly lower (p<0.05 in groups C (10% and D (20% compared to groups A (90% and B (80%. CONCLUSION: The use of non-irritant baby shampoos does not seem to eliminate the risk of cataract formation and these should even be used more carefully as the non-irritant shampoo will have more contact with the eye. [TAF Prev Med Bull 2008; 7(1.000: 1-6

  20. Microbiota-gut-brain axis and the central nervous system

    OpenAIRE

    Zhu, Xiqun; Han, Yong; Du, Jing; Liu, Renzhong; Jin, Ketao; Yi, Wei

    2017-01-01

    The gut and brain form the gut-brain axis through bidirectional nervous, endocrine, and immune communications. Changes in one of the organs will affect the other organs. Disorders in the composition and quantity of gut microorganisms can affect both the enteric nervous system and the central nervous system (CNS), thereby indicating the existence of a microbiota-gut-brain axis. Due to the intricate interactions between the gut and the brain, gut symbiotic microorganisms are closely associated ...

  1. Mycotoxin: Its Impact on Gut Health and Microbiota

    Science.gov (United States)

    Liew, Winnie-Pui-Pui; Mohd-Redzwan, Sabran

    2018-01-01

    The secondary metabolites produced by fungi known as mycotoxins, are capable of causing mycotoxicosis (diseases and death) in human and animals. Contamination of feedstuffs as well as food commodities by fungi occurs frequently in a natural manner and is accompanied by the presence of mycotoxins. The occurrence of mycotoxins' contamination is further stimulated by the on-going global warming as reflected in some findings. This review comprehensively discussed the role of mycotoxins (trichothecenes, zearalenone, fumonisins, ochratoxins, and aflatoxins) toward gut health and gut microbiota. Certainly, mycotoxins cause perturbation in the gut, particularly in the intestinal epithelial. Recent insights have generated an entirely new perspective where there is a bi-directional relationship exists between mycotoxins and gut microbiota, thus suggesting that our gut microbiota might be involved in the development of mycotoxicosis. The bacteria–xenobiotic interplay for the host is highlighted in this review article. It is now well established that a healthy gut microbiota is largely responsible for the overall health of the host. Findings revealed that the gut microbiota is capable of eliminating mycotoxin from the host naturally, provided that the host is healthy with a balance gut microbiota. Moreover, mycotoxins have been demonstrated for modulation of gut microbiota composition, and such alteration in gut microbiota can be observed up to species level in some of the studies. Most, if not all, of the reported effects of mycotoxins, are negative in terms of intestinal health, where beneficial bacteria are eliminated accompanied by an increase of the gut pathogen. The interactions between gut microbiota and mycotoxins have a significant role in the development of mycotoxicosis, particularly hepatocellular carcinoma. Such knowledge potentially drives the development of novel and innovative strategies for the prevention and therapy of mycotoxin contamination and

  2. Mycotoxin: Its Impact on Gut Health and Microbiota

    Directory of Open Access Journals (Sweden)

    Winnie-Pui-Pui Liew

    2018-02-01

    Full Text Available The secondary metabolites produced by fungi known as mycotoxins, are capable of causing mycotoxicosis (diseases and death in human and animals. Contamination of feedstuffs as well as food commodities by fungi occurs frequently in a natural manner and is accompanied by the presence of mycotoxins. The occurrence of mycotoxins' contamination is further stimulated by the on-going global warming as reflected in some findings. This review comprehensively discussed the role of mycotoxins (trichothecenes, zearalenone, fumonisins, ochratoxins, and aflatoxins toward gut health and gut microbiota. Certainly, mycotoxins cause perturbation in the gut, particularly in the intestinal epithelial. Recent insights have generated an entirely new perspective where there is a bi-directional relationship exists between mycotoxins and gut microbiota, thus suggesting that our gut microbiota might be involved in the development of mycotoxicosis. The bacteria–xenobiotic interplay for the host is highlighted in this review article. It is now well established that a healthy gut microbiota is largely responsible for the overall health of the host. Findings revealed that the gut microbiota is capable of eliminating mycotoxin from the host naturally, provided that the host is healthy with a balance gut microbiota. Moreover, mycotoxins have been demonstrated for modulation of gut microbiota composition, and such alteration in gut microbiota can be observed up to species level in some of the studies. Most, if not all, of the reported effects of mycotoxins, are negative in terms of intestinal health, where beneficial bacteria are eliminated accompanied by an increase of the gut pathogen. The interactions between gut microbiota and mycotoxins have a significant role in the development of mycotoxicosis, particularly hepatocellular carcinoma. Such knowledge potentially drives the development of novel and innovative strategies for the prevention and therapy of mycotoxin

  3. A Conceptual Model of Irritability Following Traumatic Brain Injury: A Qualitative, Participatory Research Study.

    Science.gov (United States)

    Hammond, Flora M; Davis, Christine; Cook, James R; Philbrick, Peggy; Hirsch, Mark A

    2016-01-01

    Individuals with a history of traumatic brain injury (TBI) may have chronic problems with irritability, which can negatively affect their lives. (1) To describe the experience (thoughts and feelings) of irritability from the perspectives of multiple people living with or affected by the problem, and (2) to develop a conceptual model of irritability. Qualitative, participatory research. Forty-four stakeholders (individuals with a history of TBI, family members, community professionals, healthcare providers, and researchers) divided into 5 focus groups. Each group met 10 times to discuss the experience of irritability following TBI. Data were coded using grounded theory to develop themes, metacodes, and theories. Not applicable. A conceptual model emerged in which irritability has 5 dimensions: affective (related to moods and feelings); behavioral (especially in areas of self-regulation, impulse control, and time management); cognitive-perceptual (self-talk and ways of seeing the world); relational issues (interpersonal and family dynamics); and environmental (including environmental stimuli, change, disruptions in routine, and cultural expectations). This multidimensional model provides a framework for assessment, treatment, and future research aimed at better understanding irritability, as well as the development of assessment tools and treatment interventions.

  4. Cellulose digestion in primitive hexapods: Effect of ingested antibiotics on gut microbial populations and gut cellulase levels in the firebrat,Thermobia domestica (Zygentoma, Lepismatidae).

    Science.gov (United States)

    Treves, D S; Martin, M M

    1994-08-01

    Antibiotic feeding studies were conducted on the firebrat,Thermobia domestica (Zygentoma, Lepismatidae) to determine if the insect's gut cellulases were of insect or microbial origin. Firebrats were fed diets containing either nystatin, metronidazole, streptomycin, tetracycline, or an antibiotic cocktail consisting of all four antibiotics, and then their gut microbial populations and gut cellulase levels were monitored and compared with the gut microbial populations and gut cellulase levels in firebrats feeding on antibiotic-free diets. Each antibiotic significantly reduced the firebrat's gut micro-flora. Nystatin reduced the firebrat's viable gut fungi by 89%. Tetracycline and the antibiotic cocktail reduced the firebrat's viable gut bacteria by 81% and 67%, respectively, and metronidazole, streptomycin, tetracycline, and the antibiotic cocktail reduced the firebrat's total gut flora by 35%, 32%, 55%, and 64%, respectively. Although antibiotics significantly reduced the firebrat's viable and total gut flora, gut cellulase levels in firebrats fed antibiotics were not significantly different from those in firebrats on an antibiotic-free diet. Furthermore, microbial populations in the firebrat's gut decreased significantly over time, even in firebrats feeding on the antibiotic-free diet, without corresponding decreases in gut cellulase levels. Based on this evidence, we conclude that the gut cellulases of firebrats are of insect origin. This conclusion implies that symbiont-independent cellulose digestion is a primitive trait in insects and that symbiont-mediated cellulose digestion is a derived condition.

  5. Radiative breaking scenario for the GUT gauge symmetry

    International Nuclear Information System (INIS)

    Fukuyama, T.; Kikuchi, T.

    2006-01-01

    The origin of the grand unified theory (GUT) scale from the top-down perspective is explored. The GUT gauge symmetry is broken by the renormalization group effects, which is an extension of the radiative electroweak symmetry breaking scenario to the GUT models. That is, in the same way as the origin of the electroweak scale, the GUT scale is generated from the Planck scale through the radiative corrections to the soft supersymmetry breaking mass parameters. This mechanism is applied to a perturbative SO(10) GUT model, recently proposed by us. In the SO(10) model, the relation between the GUT scale and the Planck scale can naturally be realized by using order-one coupling constants. (orig.)

  6. Skin irritation, false positives and the local lymph node assay: a guideline issue?

    Science.gov (United States)

    Basketter, David A; Kimber, Ian

    2011-10-01

    Since the formal validation and regulatory acceptance of the local lymph node assay (LLNA) there have been commentaries suggesting that the irritant properties of substances can give rise to false positives. As toxicology aspires to progress rapidly towards the age of in vitro alternatives, it is of increasing importance that issues relating to assay selectivity and performance are understood fully, and that true false positive responses are distinguished clearly from those that are simply unpalatable. In the present review, we have focused on whether skin irritation per se is actually a direct cause of true false positive results in the LLNA. The body of published work has been examined critically and considered in relation to our current understanding of the mechanisms of skin irritation and skin sensitisation. From these analyses it is very clear that, of itself, skin irritation is not a cause of false positive results. The corollary is, therefore, that limiting test concentrations in the LLNA for the purpose of avoiding skin irritation may lead, unintentionally, to false negatives. Where a substance is a true false positive in the LLNA, the classic example being sodium lauryl sulphate, explanations for that positivity will have to reach beyond the seductive, but incorrect, recourse to its skin irritation potential. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. No-scale SU(5) super-GUTs

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, John [King' s College London, Theoretical Physics and Cosmology Group, Department of Physics, London (United Kingdom); CERN, Theoretical Physics Department, Geneva 23 (Switzerland); Evans, Jason L. [KIAS, School of Physics, Seoul (Korea, Republic of); Nagata, Natsumi [University of Tokyo, Department of Physics, Tokyo, Bunkyo-ku (Japan); Nanopoulos, Dimitri V. [Texas A and M University, George P. and Cynthia W. Mitchell Institute for Fundamental Physics and Astronomy, College Station, TX (United States); Houston Advanced Research Center (HARC), Astroparticle Physics Group, Woodlands, TX (United States); Academy of Athens, Division of Natural Sciences, Athens (Greece); Olive, Keith A. [University of Minnesota, School of Physics and Astronomy, William I. Fine Theoretical Physics Institute, Minneapolis, MN (United States)

    2017-04-15

    We reconsider the minimal SU(5) grand unified theory (GUT) in the context of no-scale supergravity inspired by string compactification scenarios, assuming that the soft supersymmetry-breaking parameters satisfy universality conditions at some input scale M{sub in} above the GUT scale M{sub GUT}. When setting up such a no-scale super-GUT model, special attention must be paid to avoiding the Scylla of rapid proton decay and the Charybdis of an excessive density of cold dark matter, while also having an acceptable mass for the Higgs boson. We do not find consistent solutions if none of the matter and Higgs fields are assigned to twisted chiral supermultiplets, even in the presence of Giudice-Masiero terms. However, consistent solutions may be found if at least one fiveplet of GUT Higgs fields is assigned to a twisted chiral supermultiplet, with a suitable choice of modular weights. Spin-independent dark matter scattering may be detectable in some of these consistent solutions. (orig.)

  8. Microbiota-Brain-Gut Axis and Neurodegenerative Diseases.

    Science.gov (United States)

    Quigley, Eamonn M M

    2017-10-17

    The purposes of this review were as follows: first, to provide an overview of the gut microbiota and its interactions with the gut and the central nervous system (the microbiota-gut-brain axis) in health, second, to review the relevance of this axis to the pathogenesis of neurodegenerative diseases, such as Parkinson's disease, and, finally, to assess the potential for microbiota-targeted therapies. Work on animal models has established the microbiota-gut-brain axis as a real phenomenon; to date, the evidence for its operation in man has been limited and has been confronted by considerable logistical challenges. Animal and translational models have incriminated a disturbed gut microbiota in a number of CNS disorders, including Parkinson's disease; data from human studies is scanty. While a theoretical basis can be developed for the use of microbiota-directed therapies in neurodegenerative disorders, support is yet to come from high-quality clinical trials. In theory, a role for the microbiota-gut-brain axis is highly plausible; clinical confirmation is awaited.

  9. Clorazepate

    Science.gov (United States)

    ... asleep or staying asleep, irritability, diarrhea, muscle aches, memory problems, seizures, confusion, uncontrollable shaking of a part ... is important to keep all medication out of sight and reach of children as many containers (such ...

  10. Women and Mental Health

    Science.gov (United States)

    ... that are not there Extremely high and low moods Aches, headaches, or digestive problems without a clear cause Irritability Social withdrawal Thoughts of suicide Mental disorders can be treated : If you are unsure where ...

  11. Microbiota-gut-brain axis and the central nervous system.

    Science.gov (United States)

    Zhu, Xiqun; Han, Yong; Du, Jing; Liu, Renzhong; Jin, Ketao; Yi, Wei

    2017-08-08

    The gut and brain form the gut-brain axis through bidirectional nervous, endocrine, and immune communications. Changes in one of the organs will affect the other organs. Disorders in the composition and quantity of gut microorganisms can affect both the enteric nervous system and the central nervous system (CNS), thereby indicating the existence of a microbiota-gut-brain axis. Due to the intricate interactions between the gut and the brain, gut symbiotic microorganisms are closely associated with various CNS diseases, such as Parkinson's disease, Alzheimer's disease, schizophrenia, and multiple sclerosis. In this paper, we will review the latest advances of studies on the correlation between gut microorganisms and CNS functions & diseases.

  12. Behavioral Interventions for Anger, Irritability, and Aggression in Children and Adolescents.

    Science.gov (United States)

    Sukhodolsky, Denis G; Smith, Stephanie D; McCauley, Spencer A; Ibrahim, Karim; Piasecka, Justyna B

    2016-02-01

    Anger, irritability, and aggression are among the most common reasons for child mental health referrals. This review is focused on two forms of behavioral interventions for these behavioral problems: Parent management training (PMT) and cognitive-behavioral therapy (CBT). First, we provide an overview of anger/irritability and aggression as the treatment targets of behavioral interventions, followed by a discussion of the general principles and techniques of these treatment modalities. Then we discuss our current work concerning the transdiagnostic approach to CBT for anger, irritability, and aggression. PMT is aimed at improving aversive patterns of family interactions that engender children's disruptive behavior. CBT targets deficits in emotion regulation and social problem-solving that are associated with aggressive behavior. Both forms of treatment have received extensive support in randomized controlled trials. Given that anger/irritability and aggressive behavior are common in children with a variety of psychiatric diagnoses, a transdiagnostic approach to CBT for anger and aggression is described in detail. PMT and CBT have been well studied in randomized controlled trials in children with disruptive behavior disorders, and studies of transdiagnostic approaches to CBT for anger and aggression are currently underway. More work is needed to develop treatments for other types of aggressive behavior (e.g., relational aggression) that have been relatively neglected in clinical research. The role of callous-unemotional traits in response to behavioral interventions and treatment of irritability in children with anxiety and mood disorders also warrants further investigation.

  13. Functional Characterization of CCHamide and Muscarinic Acetylcholine Receptor Signalling in Drosophila melanogaster

    DEFF Research Database (Denmark)

    Ren, Guilin Robin

    G-protein coupled receptors (GPCRs) constitute a large and ancient superfamily of membraneproteins responsible for the transduction of extracellular signals to the inside of the cells. In thisPh.D. thesis, Drosophila melanogaster (Dm) was used as a model organism to investigate a numberof topics...... is a newly discovered insect peptide hormone. The function of this novel peptide hasnot been well characterised. In this Ph.D. thesis, I identified CCHamide-2 peptides in endocrinecells of the gut and neurones of the brain of larvae and endocrine cells of the gut of adultDrosophila. Behavioural assays...... little is known about muscarinic acetylcholine receptorsignalling in insects. In this study, I found that two types of mAChRs occur in D. melanogaster, onecoupling to Gq (A-type) and the other to Gi (B-type). Both A- and B-type Dm-mAChRs can beactivated by acetylcholine (ACh), but the classical...

  14. The gut microbiota and inflammatory noncommunicable diseases

    DEFF Research Database (Denmark)

    West, Christina E; Renz, Harald; Jenmalm, Maria C

    2015-01-01

    Rapid environmental transition and modern lifestyles are likely driving changes in the biodiversity of the human gut microbiota. With clear effects on physiologic, immunologic, and metabolic processes in human health, aberrations in the gut microbiome and intestinal homeostasis have the capacity...... for neurodevelopment and mental health. These diverse multisystem influences have sparked interest in strategies that might favorably modulate the gut microbiota to reduce the risk of many NCDs. For example, specific prebiotics promote favorable intestinal colonization, and their fermented products have anti....... In human subjects it has been successfully used in cases of Clostridium difficile infection and IBD, although controlled trials are lacking for IBD. Here we discuss relationships between gut colonization and inflammatory NCDs and gut microbiota modulation strategies for their treatment and prevention....

  15. Inactivation of JAK2/STAT3 Signaling Axis and Downregulation of M1 mAChR Cause Cognitive Impairment in klotho Mutant Mice, a Genetic Model of Aging

    Science.gov (United States)

    Park, Seok-Joo; Shin, Eun-Joo; Min, Sun Seek; An, Jihua; Li, Zhengyi; Hee Chung, Yoon; Hoon Jeong, Ji; Bach, Jae-Hyung; Nah, Seung-Yeol; Kim, Won-Ki; Jang, Choon-Gon; Kim, Yong-Sun; Nabeshima, Yo-ichi; Nabeshima, Toshitaka; Kim, Hyoung-Chun

    2013-01-01

    We previously reported cognitive dysfunction in klotho mutant mice. In the present study, we further examined novel mechanisms involved in cognitive impairment in these mice. Significantly decreased janus kinase 2 (JAK2) and signal transducer and activator of transcription3 (STAT3) phosphorylation were observed in the hippocampus of klotho mutant mice. A selective decrease in protein expression and binding density of the M1 muscarinic cholinergic receptor (M1 mAChR) was observed in these mice. Cholinergic parameters (ie, acetylcholine (ACh), choline acetyltransferase (ChAT), and acetylcholinesterase (AChE)) and NMDAR-dependent long-term potentiation (LTP) were significantly impaired in klotho mutant mice. McN-A-343 (McN), an M1 mAChR agonist, significantly attenuated these impairments. AG490 (AG), a JAK2 inhibitor, counteracted the attenuating effects of McN, although AG did not significantly alter the McN-induced effect on AChE. Furthermore, AG significantly inhibited the attenuating effects of McN on decreased NMDAR-dependent LTP, protein kinase C βII, p-ERK, p-CREB, BDNF, and p-JAK2/p-STAT3-expression in klotho mutant mice. In addition, k252a, a BDNF receptor tyrosine kinase B (TrkB) inhibitor, significantly counteracted McN effects on decreased ChAT, ACh, and M1 mAChR and p-JAK2/p-STAT3 expression. McN-induced effects on cognitive impairment in klotho mutant mice were consistently counteracted by either AG or k252a. Our results suggest that inactivation of the JAK2/STAT3 signaling axis and M1 mAChR downregulation play a critical role in cognitive impairment observed in klotho mutant mice. PMID:23389690

  16. [Gut microbiota: Description, role and pathophysiologic implications].

    Science.gov (United States)

    Landman, C; Quévrain, E

    2016-06-01

    The human gut contains 10(14) bacteria and many other micro-organisms such as Archaea, viruses and fungi. Studying the gut microbiota showed how this entity participates to gut physiology and beyond this to human health, as a real "hidden organ". In this review, we aimed to bring information about gut microbiota, its structure, its roles and its implication in human pathology. After bacterial colonization in infant, intestinal microbial composition is unique for each individual although more than 95% can be assigned to four major phyla. The use of culture independent methods and more recently the development of high throughput sequencing allowed to depict precisely gut microbiota structure and diversity as well as its alteration in diseases. Gut microbiota is implicated in the maturation of the host immune system and in many fundamental metabolic pathways including sugars and proteins fermentation and metabolism of bile acids and xenobiotics. Imbalance of gut microbial populations or dysbiosis has important functional consequences and is implicated in many digestive diseases (inflammatory bowel diseases, colorectal cancer, etc.) but also in obesity and autism. These observations have led to a surge of studies exploring therapeutics which aims to restore gut microbiota equilibrium such as probiotics or fecal microbiota transplantation. But recent research also investigates biological activity of microbial products which could lead to interesting therapeutics leads. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  17. A note on local GUT models in F-theory

    International Nuclear Information System (INIS)

    Chen, C.-M.; Chung, Y.-C.

    2010-01-01

    We construct non-minimal GUT local models in the F-theory configuration. The gauge group on the bulk G S is one rank higher than the GUT gauge group. The line bundles on the curves are nontrivial to break G S down to the GUT gauge groups. We demonstrate examples of SU(5) GUT from G S =SU(6) and G S =SO(10), the flipped SU(5) from G S =SO(10), and the SO(10) GUT from G S =SO(12) and G S =E 6 . We obtain complete GUT matter spectra and couplings, with minimum exotic matter contents. GUT gauge group breaking to MSSM is achievable by instanton configurations.

  18. The Microbiome-Gut-Behavior Axis: Crosstalk Between the Gut Microbiome and Oligodendrocytes Modulates Behavioral Responses.

    Science.gov (United States)

    Ntranos, Achilles; Casaccia, Patrizia

    2018-01-01

    Environmental and dietary stimuli have always been implicated in brain development and behavioral responses. The gut, being the major portal of communication with the external environment, has recently been brought to the forefront of this interaction with the establishment of a gut-brain axis in health and disease. Moreover, recent breakthroughs in germ-free and antibiotic-treated mice have demonstrated the significant impact of the microbiome in modulating behavioral responses in mice and have established a more specific microbiome-gut-behavior axis. One of the mechanisms by which this axis affects social behavior is by regulating myelination at the prefrontal cortex, an important site for complex cognitive behavior planning and decision-making. The prefrontal cortex exhibits late myelination of its axonal projections that could extend into the third decade of life in humans, which make it susceptible to external influences, such as microbial metabolites. Changes in the gut microbiome were shown to alter the composition of the microbial metabolome affecting highly permeable bioactive compounds, such as p-cresol, which could impair oligodendrocyte differentiation. Dysregulated myelination in the prefrontal cortex is then able to affect behavioral responses in mice, shifting them towards social isolation. The reduced social interactions could then limit microbial exchange, which could otherwise pose a threat to the survival of the existing microbial community in the host and, thus, provide an evolutionary advantage to the specific microbial community. In this review, we will analyze the microbiome-gut-behavior axis, describe the interactions between the gut microbiome and oligodendrocytes and highlight their role in the modulation of social behavior.

  19. Microstructure of a-C:H films prepared on a microtrench and analysis of ions and radicals behavior

    Energy Technology Data Exchange (ETDEWEB)

    Hirata, Yuki; Choi, Junho, E-mail: choi@mech.t.u-tokyo.ac.jp [Department of Mechanical Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)

    2015-08-28

    Amorphous carbon films (a-C:H) were prepared on a microtrench (4-μm pitch and 4-μm depth), and the uniformity of film thickness and microstructure of the films on the top, sidewall, and bottom surfaces of the microtrench were evaluated by scanning electron microscopy and Raman spectroscopy. The a-C:H films were prepared by bipolar-type plasma based ion implantation and deposition (bipolar PBII&D), and the negative pulse voltage, which is the main parameter dominating the film structure, was changed from −1.0 to −15 kV. Moreover, the behavior of ions and radicals was analyzed simultaneously by combining the calculation methods of Particle-In-Cell/Monte Carlo Collision (PIC-MCC) and Direct Simulation Monte Carlo (DSMC) to investigate the coating mechanism for the microtrench. The results reveal that the thickness uniformity of a-C:H films improves with decreasing negative pulse voltage due to the decreasing inertia of incoming ions from the trench mouth, although the film thickness on the sidewall tends to be much smaller than that on the top and bottom surfaces of the trench. The normalized flux and the film thickness show similar behavior, i.e., the normalized flux or thickness at the bottom surface increases at low negative pulse voltages and then saturates at a certain value, whereas at the sidewall it monotonically decreases with increasing negative voltage. The microstructure of a-C:H films on the sidewall surface is very different from that on the top and bottom surfaces. The film structure at a low negative pulse voltage shifts to more of a polymer-like carbon (PLC) structure due to the lower incident energy of ions. Although the radical flux on the sidewall increases slightly, the overall film structure is not significantly changed because this film formation at a low negative voltage is originally dominated by radicals. On the other hand, the flux of radicals is dominant on the sidewall in the case of high negative pulse voltage, resulting in a

  20. Microstructure of a-C:H films prepared on a microtrench and analysis of ions and radicals behavior

    Science.gov (United States)

    Hirata, Yuki; Choi, Junho

    2015-08-01

    Amorphous carbon films (a-C:H) were prepared on a microtrench (4-μm pitch and 4-μm depth), and the uniformity of film thickness and microstructure of the films on the top, sidewall, and bottom surfaces of the microtrench were evaluated by scanning electron microscopy and Raman spectroscopy. The a-C:H films were prepared by bipolar-type plasma based ion implantation and deposition (bipolar PBII&D), and the negative pulse voltage, which is the main parameter dominating the film structure, was changed from -1.0 to -15 kV. Moreover, the behavior of ions and radicals was analyzed simultaneously by combining the calculation methods of Particle-In-Cell/Monte Carlo Collision (PIC-MCC) and Direct Simulation Monte Carlo (DSMC) to investigate the coating mechanism for the microtrench. The results reveal that the thickness uniformity of a-C:H films improves with decreasing negative pulse voltage due to the decreasing inertia of incoming ions from the trench mouth, although the film thickness on the sidewall tends to be much smaller than that on the top and bottom surfaces of the trench. The normalized flux and the film thickness show similar behavior, i.e., the normalized flux or thickness at the bottom surface increases at low negative pulse voltages and then saturates at a certain value, whereas at the sidewall it monotonically decreases with increasing negative voltage. The microstructure of a-C:H films on the sidewall surface is very different from that on the top and bottom surfaces. The film structure at a low negative pulse voltage shifts to more of a polymer-like carbon (PLC) structure due to the lower incident energy of ions. Although the radical flux on the sidewall increases slightly, the overall film structure is not significantly changed because this film formation at a low negative voltage is originally dominated by radicals. On the other hand, the flux of radicals is dominant on the sidewall in the case of high negative pulse voltage, resulting in a deviation

  1. Effect of a nicotine vaccine on nicotine binding to the beta2-nAChRs in vivo in human tobacco smokers

    Science.gov (United States)

    Esterlis, Irina; Hannestad, Jonas O.; Perkins, Evgenia; Bois, Frederic; D’Souza, D. Cyril; Tyndale, Rachel F.; Seibyl, John P.; Hatsukami, Dorothy M.; Cosgrove, Kelly P.; O’Malley, Stephanie S.

    2013-01-01

    Objective Nicotine acts in the brain to promote smoking in part by binding to the beta2-containing nicotinic acetylcholine receptors (β2*-nAChRs) and acting in the mesolimbic reward pathway. The effects of nicotine from smoking one tobacco cigarette are significant (80% of β2*-nAChRs occupied for >6h). This likely contributes to the maintenance of smoking dependence and low cessation outcomes. Development of nicotine vaccines provides potential for alternative treatments. We used [123I]5IA-85380 SPECT to evaluate the effect of 3′-AmNic-rEPA on the amount of nicotine that binds to the β2*-nAChRs in the cortical and subcortical regions in smokers. Method Eleven smokers (36years (SD=13); 19cig/day (SD=11) for 10years (SD=7) who were dependent on nicotine (Fagerström Test of Nicotine Dependence score =5.5 (SD=3); plasma nicotine 9.1 ng/mL (SD=5)) participated in 2 SPECT scan days: before and after immunization with 4–400μg doses of 3′-AmNic-rEPA. On SPECT scan days, 3 30-min baseline emission scans were obtained, followed by administration of IV nicotine (1.5mg/70kg) and up to 9 30-min emission scans. Results β2*-nAChR availability was quantified as VT/fP and nicotine binding was derived using the Lassen plot approach. Immunization led to a 12.5% reduction in nicotine binding (F=5.19, df=1,10, p=0.05). Significant positive correlations were observed between nicotine bound to β2*-nAChRs and nicotine injected before but not after vaccination (p=0.05 vs. p=0.98). There was a significant reduction in the daily number of cigarettes and desire for a cigarette (p=.01 and p=.04, respectively). Conclusions This proof-of-concept study demonstrates that immunization with nicotine vaccine can reduce the amount of nicotine binding to β2*-nAChRs and disrupt the relationship between nicotine administered vs. nicotine available to occupy β2*-nAChRs. PMID:23429725

  2. Gut-Bioreactor and Human Health in Future.

    Science.gov (United States)

    Purohit, Hemant J

    2018-03-01

    Gut-microbiome provides the complementary metabolic potential to the human system. To understand the active participation and the performance of the microbial community in human health, the concept of gut as a plug-flow reactor with the fed-batch mode of operation can provide better insight. The concept suggests the virtual compartmentalized gut with sequential stratification of the microbial community in response to a typical host genotype. It also provides the analysis plan for gut microbiome; and its relevance in developing health management options under the identified clinical conditions.

  3. Gut dysbiosis impairs recovery after spinal cord injury.

    Science.gov (United States)

    Kigerl, Kristina A; Hall, Jodie C E; Wang, Lingling; Mo, Xiaokui; Yu, Zhongtang; Popovich, Phillip G

    2016-11-14

    The trillions of microbes that exist in the gastrointestinal tract have emerged as pivotal regulators of mammalian development and physiology. Disruption of this gut microbiome, a process known as dysbiosis, causes or exacerbates various diseases, but whether gut dysbiosis affects recovery of neurological function or lesion pathology after traumatic spinal cord injury (SCI) is unknown. Data in this study show that SCI increases intestinal permeability and bacterial translocation from the gut. These changes are associated with immune cell activation in gut-associated lymphoid tissues (GALTs) and significant changes in the composition of both major and minor gut bacterial taxa. Postinjury changes in gut microbiota persist for at least one month and predict the magnitude of locomotor impairment. Experimental induction of gut dysbiosis in naive mice before SCI (e.g., via oral delivery of broad-spectrum antibiotics) exacerbates neurological impairment and spinal cord pathology after SCI. Conversely, feeding SCI mice commercial probiotics (VSL#3) enriched with lactic acid-producing bacteria triggers a protective immune response in GALTs and confers neuroprotection with improved locomotor recovery. Our data reveal a previously unknown role for the gut microbiota in influencing recovery of neurological function and neuropathology after SCI. © 2016 Kigerl et al.

  4. RAGE mediates the inactivation of nAChRs in sympathetic neurons under high glucose conditions.

    Science.gov (United States)

    Chandna, Andrew R; Nair, Manoj; Chang, Christine; Pennington, Paul R; Yamamoto, Yasuhiko; Mousseau, Darrell D; Campanucci, Verónica A

    2015-02-01

    Autonomic dysfunction is a serious complication of diabetes and can lead to cardiovascular abnormalities and premature death. It was recently proposed that autonomic dysfunction is triggered by oxidation-mediated inactivation of neuronal nicotinic acetylcholine receptors (nAChRs), impairing synaptic transmission in sympathetic ganglia and resulting in autonomic failure. We investigated whether the receptor for advanced glycation end products (RAGE) and its role in the generation of reactive oxygen species (ROS) could be contributing to the events that initiate sympathetic malfunction under high glucose conditions. Using biochemical, live imaging and electrophysiological tools we demonstrated that exposure of sympathetic neurons to high glucose increases RAGE expression and oxidative markers, and that incubation with RAGE ligands (e.g. AGEs, S100 and HMGB1) mimics both ROS elevation and nAChR inactivation. In contrast, co-treatment with either antioxidants or an anti-RAGE IgG prevented the inactivation of nAChRs. Lastly, a role for RAGE in this context was corroborated by the lack of sensitivity of sympathetic neurons from RAGE knock-out mice to high glucose. These data define a pivotal role for RAGE in initiating the events associated with exposure of sympathetic neurons to high glucose, and strongly support RAGE signaling as a potential therapeutic target in the autonomic complications associated with diabetes. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  5. Clinical and Physiological Correlates of Irritability in Depression: Results from the Netherlands Study of Depression and Anxiety

    Directory of Open Access Journals (Sweden)

    Floor E. A. Verhoeven

    2011-01-01

    Full Text Available Objective. Irritable and nonirritable depressed patients differ on demographic and clinical characteristics. We investigated whether this extends to psychological and physiological measures. Method. We compared irritable and nonirritable unipolar depressed patients on symptomatology, personality, and (psychophysiological measures (cortisol, cholesterol, and heart rate variability. Symptomatology was reassessed after one year, and we also compared depressed patients who were irritable or non-irritable at both time points (Irr++ versus Irr−−. Results. Almost half (46%; N=420 of the sample was classified as irritable. These patients scored higher on depression severity, anxiety, hypomanic symptoms, and psychological variables. No differences were observed on physiological markers after correction for depression severity. The same pattern was found when comparing Irr++ and Irr−− groups. Conclusion. Irritable and non-irritable depressed patients differ on clinical and psychological variables, but not on the currently investigated physiological markers. The clinical relevance of the distinction and the significance of the hypomanic symptoms remain to be demonstrated.

  6. Influence of gut microbiota on neuropsychiatric disorders.

    Science.gov (United States)

    Cenit, María Carmen; Sanz, Yolanda; Codoñer-Franch, Pilar

    2017-08-14

    The last decade has witnessed a growing appreciation of the fundamental role played by an early assembly of a diverse and balanced gut microbiota and its subsequent maintenance for future health of the host. Gut microbiota is currently viewed as a key regulator of a fluent bidirectional dialogue between the gut and the brain (gut-brain axis). A number of preclinical studies have suggested that the microbiota and its genome (microbiome) may play a key role in neurodevelopmental and neurodegenerative disorders. Furthermore, alterations in the gut microbiota composition in humans have also been linked to a variety of neuropsychiatric conditions, including depression, autism and Parkinson's disease. However, it is not yet clear whether these changes in the microbiome are causally related to such diseases or are secondary effects thereof. In this respect, recent studies in animals have indicated that gut microbiota transplantation can transfer a behavioral phenotype, suggesting that the gut microbiota may be a modifiable factor modulating the development or pathogenesis of neuropsychiatric conditions. Further studies are warranted to establish whether or not the findings of preclinical animal experiments can be generalized to humans. Moreover, although different communication routes between the microbiota and brain have been identified, further studies must elucidate all the underlying mechanisms involved. Such research is expected to contribute to the design of strategies to modulate the gut microbiota and its functions with a view to improving mental health, and thus provide opportunities to improve the management of psychiatric diseases. Here, we review the evidence supporting a role of the gut microbiota in neuropsychiatric disorders and the state of the art regarding the mechanisms underlying its contribution to mental illness and health. We also consider the stages of life where the gut microbiota is more susceptible to the effects of environmental stressors, and

  7. Hadronic EDM constraints on orbifold GUTs

    International Nuclear Information System (INIS)

    Hisano, Junji; Kakizaki, Mitsuru; Nagai, Minoru

    2005-01-01

    We point out that the null results of the hadronic electric dipole moment (EDM) searches constrain orbifold grand unified theories (GUTs), where the GUT symmetry and supersymmetry (SUSY) are both broken by boundary conditions in extra dimensions and it leads to rich fermion and sfermion flavor structures. A marginal chromoelectric dipole moment (CEDM) of the up quark is induced by the misalignment between the CP violating left- and right-handed up-type squark mixings, in contrast to the conventional four-dimensional SUSY GUTs. The up quark CEDM constraint is found to be as strong as those from charged lepton flavor violation (LFV) searches. The interplay between future EDM and LFV experiments will probe the structures of the GUTs and the SUSY breaking mediation mechanism

  8. The gut microbiome in atherosclerotic cardiovascular disease

    DEFF Research Database (Denmark)

    Jie, Zhuye; Xia, Huihua; Zhong, Shi-Long

    2017-01-01

    The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals...... with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular......), with liver cirrhosis, and rheumatoid arthritis. Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases.The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform...

  9. Convergence of neuro-endocrine-immune pathways in the pathophysiology of irritable bowel syndrome.

    Science.gov (United States)

    Buckley, Maria M; O'Mahony, Siobhain M; O'Malley, Dervla

    2014-07-21

    Disordered signalling between the brain and the gut are generally accepted to underlie the functional bowel disorder, irritable bowel syndrome (IBS). However, partly due to the lack of disease-defining biomarkers, understanding the aetiology of this complex and multifactorial disease remains elusive. This common gastrointestinal disorder is characterised by alterations in bowel habit such as diarrhoea and/or constipation, bloating and abdominal pain, and symptom exacerbation has been linked with periods of stress, both psychosocial and infection-related. Indeed, a high level of comorbidity exists between IBS and stress-related mood disorders such as anxiety and depression. Moreover, studies have observed alterations in autonomic output and neuro-endocrine signalling in IBS patients. Accumulating evidence indicates that a maladaptive stress response, probably mediated by the stress hormone, corticotropin-releasing factor contributes to the initiation, persistence and severity of symptom flares. Other risk factors for developing IBS include a positive family history, childhood trauma, dietary factors and prior gastrointestinal infection. An emerging role has been attributed to the importance of immune factors in the pathophysiology of IBS with evidence of altered cytokine profiles and increased levels of mucosal immune cells. These factors have also been shown to have direct effects on neural signalling. This review discusses how pathological changes in neural, immune and endocrine pathways, and communication between these systems, contribute to symptom flares in IBS.

  10. Alterations of the Gut Microbiome in Hypertension

    Directory of Open Access Journals (Sweden)

    Qiulong Yan

    2017-08-01

    Full Text Available Introduction: Human gut microbiota is believed to be directly or indirectly involved in cardiovascular diseases and hypertension. However, the identification and functional status of the hypertension-related gut microbe(s have not yet been surveyed in a comprehensive manner.Methods: Here we characterized the gut microbiome in hypertension status by comparing fecal samples of 60 patients with primary hypertension and 60 gender-, age-, and body weight-matched healthy controls based on whole-metagenome shotgun sequencing.Results: Hypertension implicated a remarkable gut dysbiosis with significant reduction in within-sample diversity and shift in microbial composition. Metagenome-wide association study (MGWAS revealed 53,953 microbial genes that differ in distribution between the patients and healthy controls (false discovery rate, 0.05 and can be grouped into 68 clusters representing bacterial species. Opportunistic pathogenic taxa, such as, Klebsiella spp., Streptococcus spp., and Parabacteroides merdae were frequently distributed in hypertensive gut microbiome, whereas the short-chain fatty acid producer, such as, Roseburia spp. and Faecalibacterium prausnitzii, were higher in controls. The number of hypertension-associated species also showed stronger correlation to the severity of disease. Functionally, the hypertensive gut microbiome exhibited higher membrane transport, lipopolysaccharide biosynthesis and steroid degradation, while in controls the metabolism of amino acid, cofactors and vitamins was found to be higher. We further provided the microbial markers for disease discrimination and achieved an area under the receiver operator characteristic curve (AUC of 0.78, demonstrating the potential of gut microbiota in prediction of hypertension.Conclusion: These findings represent specific alterations in microbial diversity, genes, species and functions of the hypertensive gut microbiome. Further studies on the causality relationship between

  11. Introduction to the human gut microbiota.

    Science.gov (United States)

    Thursby, Elizabeth; Juge, Nathalie

    2017-05-16

    The human gastrointestinal (GI) tract harbours a complex and dynamic population of microorganisms, the gut microbiota, which exert a marked influence on the host during homeostasis and disease. Multiple factors contribute to the establishment of the human gut microbiota during infancy. Diet is considered as one of the main drivers in shaping the gut microbiota across the life time. Intestinal bacteria play a crucial role in maintaining immune and metabolic homeostasis and protecting against pathogens. Altered gut bacterial composition (dysbiosis) has been associated with the pathogenesis of many inflammatory diseases and infections. The interpretation of these studies relies on a better understanding of inter-individual variations, heterogeneity of bacterial communities along and across the GI tract, functional redundancy and the need to distinguish cause from effect in states of dysbiosis. This review summarises our current understanding of the development and composition of the human GI microbiota, and its impact on gut integrity and host health, underlying the need for mechanistic studies focusing on host-microbe interactions. © 2017 The Author(s).

  12. [Glucose homeostasis and gut-brain connection].

    Science.gov (United States)

    De Vadder, Filipe; Mithieux, Gilles

    2015-02-01

    Since the XIX(th) century, the brain has been known for its role in regulating food intake (via the control of hunger sensation) and glucose homeostasis. Further interest has come from the discovery of gut hormones, which established a clear link between the gut and the brain in regulating glucose and energy homeostasis. The brain has two particular structures, the hypothalamus and the brainstem, which are sensitive to information coming either from peripheral organs or from the gut (via circulating hormones or nutrients) about the nutritional status of the organism. However, the efforts for a better understanding of these mechanisms have allowed to unveil a new gut-brain neural axis as a key regulator of the metabolic status of the organism. Certain nutrients control the hypothalamic homeostatic function via this axis. In this review, we describe how the gut is connected to the brain via different neural pathways, and how the interplay between these two organs drives the energy balance. © 2015 médecine/sciences – Inserm.

  13. Gut microbiota controls adipose tissue expansion, gut barrier and glucose metabolism: novel insights into molecular targets and interventions using prebiotics.

    Science.gov (United States)

    Geurts, L; Neyrinck, A M; Delzenne, N M; Knauf, C; Cani, P D

    2014-03-01

    Crosstalk between organs is crucial for controlling numerous homeostatic systems (e.g. energy balance, glucose metabolism and immunity). Several pathological conditions, such as obesity and type 2 diabetes, are characterised by a loss of or excessive inter-organ communication that contributes to the development of disease. Recently, we and others have identified several mechanisms linking the gut microbiota with the development of obesity and associated disorders (e.g. insulin resistance, type 2 diabetes, hepatic steatosis). Among these, we described the concept of metabolic endotoxaemia (increase in plasma lipopolysaccharide levels) as one of the triggering factors leading to the development of metabolic inflammation and insulin resistance. Growing evidence suggests that gut microbes contribute to the onset of low-grade inflammation characterising these metabolic disorders via mechanisms associated with gut barrier dysfunctions. We have demonstrated that enteroendocrine cells (producing glucagon-like peptide-1, peptide YY and glucagon-like peptide-2) and the endocannabinoid system control gut permeability and metabolic endotoxaemia. Recently, we hypothesised that specific metabolic dysregulations occurring at the level of numerous organs (e.g. gut, adipose tissue, muscles, liver and brain) rely from gut microbiota modifications. In this review, we discuss the mechanisms linking gut permeability, adipose tissue metabolism, and glucose homeostasis, and recent findings that show interactions between the gut microbiota, the endocannabinoid system and the apelinergic system. These specific systems are discussed in the context of the gut-to-peripheral organ axis (intestine, adipose tissue and brain) and impacts on metabolic regulation. In the present review, we also briefly describe the impact of a variety of non-digestible nutrients (i.e. inulin-type fructans, arabinoxylans, chitin glucans and polyphenols). Their effects on the composition of the gut microbiota and

  14. The role of dermal irritation in the skin tumor promoting activity of petroleum middle distillates.

    Science.gov (United States)

    Nessel, C S; Freeman, J J; Forgash, R C; McKee, R H

    1999-05-01

    Petroleum middle distillates (PMDs), a class of hydrocarbons which boil between 350-700 degrees F, are tumor promoters in mouse skin. The promotional activity is produced under conditions that also result in local changes, including chronic irritation and epidermal hyperplasia. The present study was conducted by comparing equal weekly doses of irritating and minimally or nonirritating test materials, to assess whether tumor promotion was a secondary response to these effects. Four PMDs, C10-C14 normal paraffins (NP), lightly refined paraffinic oil (LRPO), Jet Fuel A (JF), and steam-cracked gas oil (SCGO), were evaluated. Test materials were applied undiluted (2x/week) or as 28.6% (7x/week) or 50% (4x/week) concentrations in mineral oil for 52 weeks following initiation with dimethylbenzanthracene (DMBA). When applied undiluted, all materials produced moderate irritation and significant increase in tumor incidence. When NP, LRPO, or JF were applied in mineral oil diluent, skin irritation was generally ameliorated and few, if any, tumors were produced. SCGO was irritating and produced a significant increase in tumor frequency when administered in mineral-oil diluent. These data indicate that the promotional activity of straight-run PMDs is likely related to chronic irritation at the application site and not to dose. Thus, when used appropriately in the absence of prolonged irritation, these materials should not present a tumorigenic hazard to humans.

  15. The human gut microbiota and virome: Potential therapeutic implications.

    Science.gov (United States)

    Scarpellini, Emidio; Ianiro, Gianluca; Attili, Fabia; Bassanelli, Chiara; De Santis, Adriano; Gasbarrini, Antonio

    2015-12-01

    Human gut microbiota is a complex ecosystem with several functions integrated in the host organism (metabolic, immune, nutrients absorption, etc.). Human microbiota is composed by bacteria, yeasts, fungi and, last but not least, viruses, whose composition has not been completely described. According to previous evidence on pathogenic viruses, the human gut harbours plant-derived viruses, giant viruses and, only recently, abundant bacteriophages. New metagenomic methods have allowed to reconstitute entire viral genomes from the genetic material spread in the human gut, opening new perspectives on the understanding of the gut virome composition, the importance of gut microbiome, and potential clinical applications. This review reports the latest evidence on human gut "virome" composition and its function, possible future therapeutic applications in human health in the context of the gut microbiota, and attempts to clarify the role of the gut "virome" in the larger microbial ecosystem. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  16. Enterotypes influence temporal changes in gut microbiota

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Licht, Tine Rask; Kellebjerg Poulsen, Sanne

    The human gut microbiota plays an important role for human health. The question is whether we can modulate the gut microbiota by changing diet. During a 6-month, randomised, controlled dietary intervention, the effect of consuming a diet following the New Nordic Diet recommendations (NND......) as opposed to Average Danish Diet (ADD) on the gut microbiota in humans (n=62) was investigated. Quantitative PCR analysis showed that the microbiota did not change significantly by the intervention. Nevertheless, by stratifying subjects into two enterotypes, distinguished by the Prevotella/Bacteroides ratio...... (P/B), we were able to detect significant changes in the gut microbiota composition resulting from the interventions. Subjects with a high-P/B experienced more pronounced changes in the gut microbiota composition than subjects with a low-P/B. The study is the first to indicate that enterotypes...

  17. Microbiota in fermented feed and swine gut.

    Science.gov (United States)

    Wang, Cheng; Shi, Changyou; Zhang, Yu; Song, Deguang; Lu, Zeqing; Wang, Yizhen

    2018-04-01

    Development of alternatives to antibiotic growth promoters (AGP) used in swine production requires a better understanding of their impacts on the gut microbiota. Supplementing fermented feed (FF) in swine diets as a novel nutritional strategy to reduce the use of AGP and feed price, can positively affect the porcine gut microbiota, thereby improving pig productivities. Previous studies have noted the potential effects of FF on the shift in benefit of the swine microbiota in different regions of the gastrointestinal tract (GIT). The positive influences of FF on swine gut microbiota may be due to the beneficial effects of both pre- and probiotics. Necessarily, some methods should be adopted to properly ferment and evaluate the feed and avoid undesired problems. In this mini-review, we mainly discuss the microbiota in both fermented feed and swine gut and how FF influences swine gut microbiota.

  18. Gut proteases target Yersinia invasin in vivo

    Directory of Open Access Journals (Sweden)

    Freund Sandra

    2011-04-01

    Full Text Available Abstract Background Yersinia enterocolitica is a common cause of food borne gastrointestinal disease. After oral uptake, yersiniae invade Peyer's patches of the distal ileum. This is accomplished by the binding of the Yersinia invasin to β1 integrins on the apical surface of M cells which overlie follicle associated lymphoid tissue. The gut represents a barrier that severely limits yersiniae from reaching deeper tissues such as Peyer's patches. We wondered if gut protease attack on invasion factors could contribute to the low number of yersiniae invading Peyer's patches. Findings Here we show that invasin is rapidly degraded in vivo by gut proteases in the mouse infection model. In vivo proteolytic degradation is due to proteolysis by several gut proteases such as trypsin, α-chymotrypsin, pancreatic elastase, and pepsin. Protease treated yersiniae are shown to be less invasive in a cell culture model. YadA, another surface adhesin is cleaved by similar concentrations of gut proteases but Myf was not cleaved, showing that not all surface proteins are equally susceptible to degradation by gut proteases. Conclusions We demonstrate that gut proteases target important Yersinia virulence factors such as invasin and YadA in vivo. Since invasin is completely degraded within 2-3 h after reaching the small intestine of mice, it is no longer available to mediate invasion of Peyer's patches.

  19. The Gut Microbiota of Marine Fish

    Science.gov (United States)

    Egerton, Sian; Culloty, Sarah; Whooley, Jason; Stanton, Catherine; Ross, R. Paul

    2018-01-01

    The body of work relating to the gut microbiota of fish is dwarfed by that on humans and mammals. However, it is a field that has had historical interest and has grown significantly along with the expansion of the aquaculture industry and developments in microbiome research. Research is now moving quickly in this field. Much recent focus has been on nutritional manipulation and modification of the gut microbiota to meet the needs of fish farming, while trying to maintain host health and welfare. However, the diversity amongst fish means that baseline data from wild fish and a clear understanding of the role that specific gut microbiota play is still lacking. We review here the factors shaping marine fish gut microbiota and highlight gaps in the research. PMID:29780377

  20. Multislice ct in gut related pathologies

    International Nuclear Information System (INIS)

    Nadeem, A.; Shaukat, A.; Ahmad, M.W.; Amin, Y.

    2007-01-01

    The objective of this study is to evaluate the effectiveness of Multislice CT in Gut related pathologies. 50 consecutive patients, referred from surgical and medical departments, with gut pathology suspicion were scanned in this respect on Toshiba MSCT 4 slice Aquilion. Patients were. 100 ml iodinated non ionic IV contrast was given. Preferably water was used as oral contrast and oral iodinated contrast was used only in selective cases. As a result, 33 patients showed positive response and 17 were normal; 23 were females and 10 were males. We found following pathologies Acute Appendicitis 10, Diverticulitis 02, Inflammatory Bowel Disease 03, Small Bowel Obstruction 04, Malignant Gut masses 08, Omental Implants 05, Perforation (Duodenal) 01. It is thus concluded that MDCT has a definite role in gut pathologies especially when the ultrasound is negative. (author)

  1. The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota.

    Science.gov (United States)

    Milani, Christian; Duranti, Sabrina; Bottacini, Francesca; Casey, Eoghan; Turroni, Francesca; Mahony, Jennifer; Belzer, Clara; Delgado Palacio, Susana; Arboleya Montes, Silvia; Mancabelli, Leonardo; Lugli, Gabriele Andrea; Rodriguez, Juan Miguel; Bode, Lars; de Vos, Willem; Gueimonde, Miguel; Margolles, Abelardo; van Sinderen, Douwe; Ventura, Marco

    2017-12-01

    The human gut microbiota is engaged in multiple interactions affecting host health during the host's entire life span. Microbes colonize the neonatal gut immediately following birth. The establishment and interactive development of this early gut microbiota are believed to be (at least partially) driven and modulated by specific compounds present in human milk. It has been shown that certain genomes of infant gut commensals, in particular those of bifidobacterial species, are genetically adapted to utilize specific glycans of this human secretory fluid, thus representing a very intriguing example of host-microbe coevolution, where both partners are believed to benefit. In recent years, various metagenomic studies have tried to dissect the composition and functionality of the infant gut microbiome and to explore the distribution across the different ecological niches of the infant gut biogeography of the corresponding microbial consortia, including those corresponding to bacteria and viruses, in healthy and ill subjects. Such analyses have linked certain features of the microbiota/microbiome, such as reduced diversity or aberrant composition, to intestinal illnesses in infants or disease states that are manifested at later stages of life, including asthma, inflammatory bowel disease, and metabolic disorders. Thus, a growing number of studies have reported on how the early human gut microbiota composition/development may affect risk factors related to adult health conditions. This concept has fueled the development of strategies to shape the infant microbiota composition based on various functional food products. In this review, we describe the infant microbiota, the mechanisms that drive its establishment and composition, and how microbial consortia may be molded by natural or artificial interventions. Finally, we discuss the relevance of key microbial players of the infant gut microbiota, in particular bifidobacteria, with respect to their role in health and

  2. Nurse-Administered, Gut-Directed Hypnotherapy in IBS: Efficacy and Factors Predicting a Positive Response.

    Science.gov (United States)

    Lövdahl, Jenny; Ringström, Gisela; Agerforz, Pia; Törnblom, Hans; Simrén, Magnus

    2015-07-01

    Hypnotherapy is an effective treatment in irritable bowel syndrome (IBS). It is often delivered by a psychotherapist and is costly and time consuming. Nurse-administered hypnotherapy could increase availability and reduce costs. In this study the authors evaluate the effectiveness of nurse-administered, gut-directed hypnotherapy and identify factors predicting treatment outcome. Eighty-five patients were included in the study. Participants received hypnotherapy by a nurse once/week for 12 weeks. Patients reported marked improvement in gastrointestinal (GI) and extra-colonic symptoms after treatment, as well as a reduction in GI-specific anxiety, general anxiety, and depression. Fifty-eight percent were responders after the 12 weeks treatment period, and of these 82% had a favorable clinical response already at week 6. Women were more likely than men to respond favorably to the treatment. Nurse-administered hypnotherapy is an effective treatment for IBS. Being female and reporting a favorable response to treatment by week 6 predicted a positive treatment response at the end of the 12 weeks treatment period.

  3. Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases.

    Science.gov (United States)

    Yarandi, Shadi S; Peterson, Daniel A; Treisman, Glen J; Moran, Timothy H; Pasricha, Pankaj J

    2016-04-30

    Gut microbiome is an integral part of the Gut-Brain axis. It is becoming increasingly recognized that the presence of a healthy and diverse gut microbiota is important to normal cognitive and emotional processing. It was known that altered emotional state and chronic stress can change the composition of gut microbiome, but it is becoming more evident that interaction between gut microbiome and central nervous system is bidirectional. Alteration in the composition of the gut microbiome can potentially lead to increased intestinal permeability and impair the function of the intestinal barrier. Subsequently, neuro-active compounds and metabolites can gain access to the areas within the central nervous system that regulate cognition and emotional responses. Deregulated inflammatory response, promoted by harmful microbiota, can activate the vagal system and impact neuropsychological functions. Some bacteria can produce peptides or short chain fatty acids that can affect gene expression and inflammation within the central nervous system. In this review, we summarize the evidence supporting the role of gut microbiota in modulating neuropsychological functions of the central nervous system and exploring the potential underlying mechanisms.

  4. The first microbial colonizers of the human gut

    NARCIS (Netherlands)

    Milani, Christian; Duranti, Sabrina; Bottacini, Francesca; Casey, Eoghan; Turroni, Francesca; Mahony, Jennifer; Belzer, Clara; Palacio, Susana Delgado; Montes, Silvia Arboleya; Mancabelli, Leonardo; Lugli, Gabriele Andrea; Rodriguez, Juan Miguel; Bode, Lars; Vos, De Willem; Gueimonde, Miguel; Margolles, Abelardo; Sinderen, Van Douwe; Ventura, Marco

    2017-01-01

    The human gut microbiota is engaged in multiple interactions affecting host health during the host's entire life span. Microbes colonize the neonatal gut immediately following birth. The establishment and interactive development of this early gut microbiota are believed to be (at least partially)

  5. Recruitment and establishment of the gut microbiome in arctic shorebirds.

    Science.gov (United States)

    Grond, Kirsten; Lanctot, Richard B; Jumpponen, Ari; Sandercock, Brett K

    2017-12-01

    Gut microbiota play a key role in host health. Mammals acquire gut microbiota during birth, but timing of gut microbial recruitment in birds is unknown. We evaluated whether precocial chicks from three species of arctic-breeding shorebirds acquire gut microbiota before or after hatching, and then documented the rate and compositional dynamics of accumulation of gut microbiota. Contrary to earlier reports of microbial recruitment before hatching in chickens, quantitative PCR and Illumina sequence data indicated negligible microbiota in the guts of shorebird embryos before hatching. Analyses of chick feces indicated an exponential increase in bacterial abundance of guts 0-2 days post-hatch, followed by stabilization. Gut communities were characterized by stochastic recruitment and convergence towards a community dominated by Clostridia and Gammaproteobacteria. We conclude that guts of shorebird chicks are likely void of microbiota prior to hatch, but that stable gut microbiome establishes as early as 3 days of age, probably from environmental inocula. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. A catalog of the mouse gut metagenome

    DEFF Research Database (Denmark)

    Xiao, Liang; Feng, Qiang; Liang, Suisha

    2015-01-01

    laboratories and fed either a low-fat or high-fat diet. Similar to the human gut microbiome, >99% of the cataloged genes are bacterial. We identified 541 metagenomic species and defined a core set of 26 metagenomic species found in 95% of the mice. The mouse gut microbiome is functionally similar to its human......We established a catalog of the mouse gut metagenome comprising ∼2.6 million nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure high microbiome diversity, we used mouse strains of diverse genetic backgrounds, from different providers, kept in different housing...... counterpart, with 95.2% of its Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologous groups in common. However, only 4.0% of the mouse gut microbial genes were shared (95% identity, 90% coverage) with those of the human gut microbiome. This catalog provides a useful reference for future studies....

  7. Gut-directed hypnotherapy in children with irritable bowel syndrome or functional abdominal pain (syndrome): a randomized controlled trial on self exercises at home using CD versus individual therapy by qualified therapists.

    Science.gov (United States)

    Rutten, Juliette M T M; Vlieger, Arine M; Frankenhuis, Carla; George, Elvira K; Groeneweg, Michael; Norbruis, Obbe F; Tjon a Ten, Walther; Van Wering, Herbert; Dijkgraaf, Marcel G W; Merkus, Maruschka P; Benninga, Marc A

    2014-06-04

    Irritable bowel syndrome (IBS) and functional abdominal pain (syndrome) (FAP(S)) are common pediatric disorders, characterized by chronic or recurrent abdominal pain. Treatment is challenging, especially in children with persisting symptoms. Gut-directed hypnotherapy (HT) performed by a therapist has been shown to be effective in these children, but is still unavailable to many children due to costs, a lack of qualified child-hypnotherapists and because it requires a significant investment of time by child and parent(s). Home-based hypnotherapy by means of exercises on CD has been shown effective as well, and has potential benefits, such as lower costs and less time investment. The aim of this randomized controlled trial (RCT) is to compare cost-effectiveness of individual HT performed by a qualified therapist with HT by means of CD recorded self-exercises at home in children with IBS or FAP(S). 260 children, aged 8-18 years with IBS or FAP(S) according to Rome III criteria are included in this currently conducted RCT with a follow-up period of one year. Children are randomized to either 6 sessions of individual HT given by a qualified therapist over a 3-month period or HT through self-exercises at home with CD for 3 months.The primary outcome is the proportion of patients in which treatment is successful at the end of treatment and after one year follow-up. Treatment success is defined as at least 50% reduction in both abdominal pain frequency and intensity scores. Secondary outcomes include adequate relief, cost-effectiveness and effects of both therapies on depression and anxiety scores, somatization scores, QoL, pain beliefs and coping strategies. If the effectiveness of home-based HT with CD is comparable to, or only slightly lower, than HT by a therapist, this treatment may become an attractive form of therapy in children with IBS or FAP(S), because of its low costs and direct availability. Dutch Trial Register number NTR2725 (date of registration: 1 February

  8. Anxiety, Depression, and the Microbiome: A Role for Gut Peptides.

    Science.gov (United States)

    Lach, Gilliard; Schellekens, Harriet; Dinan, Timothy G; Cryan, John F

    2018-01-01

    The complex bidirectional communication between the gut and the brain is finely orchestrated by different systems, including the endocrine, immune, autonomic, and enteric nervous systems. Moreover, increasing evidence supports the role of the microbiome and microbiota-derived molecules in regulating such interactions; however, the mechanisms underpinning such effects are only beginning to be resolved. Microbiota-gut peptide interactions are poised to be of great significance in the regulation of gut-brain signaling. Given the emerging role of the gut-brain axis in a variety of brain disorders, such as anxiety and depression, it is important to understand the contribution of bidirectional interactions between peptide hormones released from the gut and intestinal bacteria in the context of this axis. Indeed, the gastrointestinal tract is the largest endocrine organ in mammals, secreting dozens of different signaling molecules, including peptides. Gut peptides in the systemic circulation can bind cognate receptors on immune cells and vagus nerve terminals thereby enabling indirect gut-brain communication. Gut peptide concentrations are not only modulated by enteric microbiota signals, but also vary according to the composition of the intestinal microbiota. In this review, we will discuss the gut microbiota as a regulator of anxiety and depression, and explore the role of gut-derived peptides as signaling molecules in microbiome-gut-brain communication. Here, we summarize the potential interactions of the microbiota with gut hormones and endocrine peptides, including neuropeptide Y, peptide YY, pancreatic polypeptide, cholecystokinin, glucagon-like peptide, corticotropin-releasing factor, oxytocin, and ghrelin in microbiome-to-brain signaling. Together, gut peptides are important regulators of microbiota-gut-brain signaling in health and stress-related psychiatric illnesses.

  9. Gut Pharmacomicrobiomics: the tip of an iceberg of complex interactions between drugs and gut-associated microbes.

    Science.gov (United States)

    Saad, Rama; Rizkallah, Mariam R; Aziz, Ramy K

    2012-11-30

    The influence of resident gut microbes on xenobiotic metabolism has been investigated at different levels throughout the past five decades. However, with the advance in sequencing and pyrotagging technologies, addressing the influence of microbes on xenobiotics had to evolve from assessing direct metabolic effects on toxins and botanicals by conventional culture-based techniques to elucidating the role of community composition on drugs metabolic profiles through DNA sequence-based phylogeny and metagenomics. Following the completion of the Human Genome Project, the rapid, substantial growth of the Human Microbiome Project (HMP) opens new horizons for studying how microbiome compositional and functional variations affect drug action, fate, and toxicity (pharmacomicrobiomics), notably in the human gut. The HMP continues to characterize the microbial communities associated with the human gut, determine whether there is a common gut microbiome profile shared among healthy humans, and investigate the effect of its alterations on health. Here, we offer a glimpse into the known effects of the gut microbiota on xenobiotic metabolism, with emphasis on cases where microbiome variations lead to different therapeutic outcomes. We discuss a few examples representing how the microbiome interacts with human metabolic enzymes in the liver and intestine. In addition, we attempt to envisage a roadmap for the future implications of the HMP on therapeutics and personalized medicine.

  10. Omega-3 fatty acids decreased irritability of patients with bipolar disorder in an add-on, open label study

    Directory of Open Access Journals (Sweden)

    Baldassano Claudia F

    2005-02-01

    Full Text Available Abstract This is a report on a 37-patient continuation study of the open ended, Omega-3 Fatty Acid (O-3FA add-on study. Subjects consisted of the original 19 patients, along with 18 new patients recruited and followed in the same fashion as the first nineteen. Subjects carried a DSM-IV-TR diagnosis of Bipolar Disorder and were visiting a Mood Disorder Clinic regularly through the length of the study. At each visit, patients' clinical status was monitored using the Clinical Monitoring Form. Subjects reported on the frequency and severity of irritability experienced during the preceding ten days; frequency was measured by way of percentage of days in which subjects experienced irritability, while severity of that irritability was rated on a Likert scale of 1 – 4 (if present. The irritability component of Young Mania Rating Scale (YMRS was also recorded quarterly on 13 of the 39 patients consistently. Patients had persistent irritability despite their ongoing pharmacologic and psychotherapy. Omega-3 Fatty Acid intake helped with the irritability component of patients suffering from bipolar disorder with a significant presenting sign of irritability. Low dose (1 to 2 grams per day, add-on O-3FA may also help with the irritability component of different clinical conditions, such as schizophrenia, borderline personality disorder and other psychiatric conditions with a common presenting sign of irritability.

  11. Copepod guts as biogeochemical hotspots in the sea

    DEFF Research Database (Denmark)

    Tang, Kam W.; Glud, Ronnie N.; Glud, Anni

    2011-01-01

    The environmental conditions inside the gut of Calanus hyperboreus and C. glacialis were measured with microelectrodes. An acidic potential hydrogen (pH) gradient was present in the gut of C. hyperboreus, and the lowest pH recorded was 5.40. The gut pH of a starved copepod decreased by 0.53 after...... the copepod resumed feeding for a few hours, indicating the secretion of acidic digestive fluid. A copepod feeding on Thalassiosira weissflogii (diatom) had slightly lower pH than that feeding on Rhodomonas salina (cryptophyte). Oxygen was undersaturated in the gut of both C. hyperboreus and C. glacialis......, with a steep gradient from the anal opening to the metasome region. The central metasome region was completely anoxic. Food remains in the gut led to a lower oxygen level, and a diatom diet induced a stronger oxygen gradient than a cryptophyte diet. The acidic and suboxic–anoxic environments of the copepod gut...

  12. Contribution of Gut Bacteria to Liver Pathobiology

    Directory of Open Access Journals (Sweden)

    Gakuhei Son

    2010-01-01

    Full Text Available Emerging evidence suggests a strong interaction between the gut microbiota and health and disease. The interactions of the gut microbiota and the liver have only recently been investigated in detail. Receiving approximately 70% of its blood supply from the intestinal venous outflow, the liver represents the first line of defense against gut-derived antigens and is equipped with a broad array of immune cells (i.e., macrophages, lymphocytes, natural killer cells, and dendritic cells to accomplish this function. In the setting of tissue injury, whereby the liver is otherwise damaged (e.g., viral infection, toxin exposure, ischemic tissue damage, etc., these same immune cell populations and their interactions with the infiltrating gut bacteria likely contribute to and promote these pathologies. The following paper will highlight recent studies investigating the relationship between the gut microbiota, liver biology, and pathobiology. Defining these connections will likely provide new targets for therapy or prevention of a wide variety of acute and chronic liver pathologies.

  13. Cigarette smoking during pregnancy regulates the expression of specific nicotinic acetylcholine receptor (nAChR) subunits in the human placenta

    Energy Technology Data Exchange (ETDEWEB)

    Machaalani, R., E-mail: rita.machaalani@sydney.edu.au [Department of Medicine, The University of Sydney, NSW 2006 (Australia); Bosch Institute, The University of Sydney, NSW 2006 (Australia); The Children' s Hospital at Westmead, NSW 2145 (Australia); Ghazavi, E. [Bosch Institute, The University of Sydney, NSW 2006 (Australia); School of Medical Sciences (Pharmacology), The University of Sydney, NSW 2006 (Australia); Hinton, T. [School of Medical Sciences (Pharmacology), The University of Sydney, NSW 2006 (Australia); Waters, K.A. [Department of Medicine, The University of Sydney, NSW 2006 (Australia); The Children' s Hospital at Westmead, NSW 2145 (Australia); Hennessy, A. [School of Medicine, University of Western Sydney, NSW 2751 (Australia); Heart Research Institute, 7 Eliza St Newtown, NSW 2042 (Australia)

    2014-05-01

    Smoking during pregnancy is associated with low birth weight, premature delivery, and neonatal morbidity and mortality. Nicotine, a major pathogenic compound of cigarette smoke, binds to the nicotinic acetylcholine receptors (nAChRs). A total of 16 nAChR subunits have been identified in mammals (9 α, 4 β, and 1 δ, γ and ε subunits). The effect of cigarette smoking on the expression of these subunits in the placenta has not yet been determined, thus constituting the aim of this study. Using RT-qPCR and western blotting, this study investigated all 16 mammalian nAChR subunits in the normal healthy human placenta, and compared mRNA and protein expressions in the placentas from smokers (n = 8) to controls (n = 8). Our data show that all 16 subunit mRNAs are expressed in the normal, non-diseased human placenta and that the expression of α2, α3, α4, α9, β2 and β4 subunits is greater than the other subunits. For mRNA, cigarette smoke exposure was associated with increased expression of the α9 subunit, and decreased expression of the δ subunit. At the protein level, expression of both α9 and δ was increased. Thus, cigarette smoking in pregnancy is sufficient to regulate nAChR subunits in the placenta, specifically α9 and δ subunits, and could contribute to the adverse effects of vasoconstriction and decreased re-epithelialisation (α9), and increased calcification and apoptosis (δ), seen in the placentas of smoking women. - Highlights: • All 16 mammalian nAChR subunits are expressed in the human placenta. • Cigarette smoking increases α9 mRNA and protein in the placenta. • Cigarette smoking decreases δ mRNA but increases δ protein in the placenta.

  14. Cigarette smoking during pregnancy regulates the expression of specific nicotinic acetylcholine receptor (nAChR) subunits in the human placenta

    International Nuclear Information System (INIS)

    Machaalani, R.; Ghazavi, E.; Hinton, T.; Waters, K.A.; Hennessy, A.

    2014-01-01

    Smoking during pregnancy is associated with low birth weight, premature delivery, and neonatal morbidity and mortality. Nicotine, a major pathogenic compound of cigarette smoke, binds to the nicotinic acetylcholine receptors (nAChRs). A total of 16 nAChR subunits have been identified in mammals (9 α, 4 β, and 1 δ, γ and ε subunits). The effect of cigarette smoking on the expression of these subunits in the placenta has not yet been determined, thus constituting the aim of this study. Using RT-qPCR and western blotting, this study investigated all 16 mammalian nAChR subunits in the normal healthy human placenta, and compared mRNA and protein expressions in the placentas from smokers (n = 8) to controls (n = 8). Our data show that all 16 subunit mRNAs are expressed in the normal, non-diseased human placenta and that the expression of α2, α3, α4, α9, β2 and β4 subunits is greater than the other subunits. For mRNA, cigarette smoke exposure was associated with increased expression of the α9 subunit, and decreased expression of the δ subunit. At the protein level, expression of both α9 and δ was increased. Thus, cigarette smoking in pregnancy is sufficient to regulate nAChR subunits in the placenta, specifically α9 and δ subunits, and could contribute to the adverse effects of vasoconstriction and decreased re-epithelialisation (α9), and increased calcification and apoptosis (δ), seen in the placentas of smoking women. - Highlights: • All 16 mammalian nAChR subunits are expressed in the human placenta. • Cigarette smoking increases α9 mRNA and protein in the placenta. • Cigarette smoking decreases δ mRNA but increases δ protein in the placenta

  15. Diet in irritable bowel syndrome

    OpenAIRE

    El-Salhy, Magdy; Gundersen, Doris Irene

    2015-01-01

    Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder that is characterized by intermittent abdominal pain/discomfort, altered bowel habits and abdominal bloating/distension. This review aimed at presenting the recent developments concerning the role of diet in the pathophysiology and management of IBS. There is no convincing evidence that IBS patients suffer from food allergy/intolerance, and there is no evidence that gluten causes the debated new diagnosis of non-coel...

  16. Early-life gut microbiome and egg allergy.

    Science.gov (United States)

    Fazlollahi, M; Chun, Y; Grishin, A; Wood, R A; Burks, A W; Dawson, P; Jones, S M; Leung, D Y M; Sampson, H A; Sicherer, S H; Bunyavanich, S

    2018-07-01

    Gut microbiota may play a role in egg allergy. We sought to examine the association between early-life gut microbiota and egg allergy. We studied 141 children with egg allergy and controls from the multicenter Consortium of Food Allergy Research study. At enrollment (age 3 to 16 months), fecal samples were collected, and clinical evaluation, egg-specific IgE measurement, and egg skin prick test were performed. Gut microbiome was profiled by 16S rRNA sequencing. Analyses for the primary outcome of egg allergy at enrollment, and the secondary outcomes of egg sensitization at enrollment and resolution of egg allergy by age 8 years, were performed using Quantitative Insights into Microbial Ecology, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States, and Statistical Analysis of Metagenomic Profiles. Compared to controls, increased alpha diversity and distinct taxa (PERMANOVA P = 5.0 × 10 -4 ) characterized the early-life gut microbiome of children with egg allergy. Genera from the Lachnospiraceae, Streptococcaceae, and Leuconostocaceae families were differentially abundant in children with egg allergy. Predicted metagenome functional analyses showed differential purine metabolism by the gut microbiota of egg-allergic subjects (Kruskal-Wallis P adj  = 0.021). Greater gut microbiome diversity and genera from Lachnospiraceae and Ruminococcaceae were associated with egg sensitization (PERMANOVA P = 5.0 × 10 -4 ). Among those with egg allergy, there was no association between early-life gut microbiota and egg allergy resolution by age 8 years. The distinct early-life gut microbiota in egg-allergic and egg-sensitized children identified by our study may point to targets for preventive or therapeutic intervention. © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  17. The gut microbiota and its relationship to diet and obesity

    Science.gov (United States)

    Clarke, Siobhan F.; Murphy, Eileen F.; Nilaweera, Kanishka; Ross, Paul R.; Shanahan, Fergus; O’Toole, Paul W.; Cotter, Paul D.

    2012-01-01

    Obesity develops from a prolonged imbalance of energy intake and energy expenditure. However, the relatively recent discovery that the composition and function of the gut microbiota impacts on obesity has lead to an explosion of interest in what is now a distinct research field. Here, research relating to the links between the gut microbiota, diet and obesity will be reviewed under five major headings: (1) the gut microbiota of lean and obese animals, (2) the composition of the gut microbiota of lean and obese humans, (3) the impact of diet on the gut microbiota, (4) manipulating the gut microbiota and (5) the mechanisms by which the gut microbiota can impact on weight gain. PMID:22572830

  18. CT-Sellink - a new method for demonstrating the gut wall

    International Nuclear Information System (INIS)

    Thiele, J.; Kloeppel, R.; Schulz, H.G.

    1993-01-01

    34 patients were examined by CT following a modified enema (CT-Sellink) in order to demonstrate the gut. By introducing a 'gut index' it is possible to define the tone of the gut providing its folds remain constant. By means of a radial density profile the gut wall can be defined objectively and in numerical terms. Gut wall thickness in the small bowel averaged 1.2 mm with a density of 51 Hu and gut wall thickness in the colon averaged 2 mm with a density of 59 Hu. (orig.) [de

  19. Irritable bowel syndrome: Is it "irritable brain" or "irritable bowel"?

    Directory of Open Access Journals (Sweden)

    Susanta Kumar Padhy

    2015-01-01

    Full Text Available Irritable bowel syndrome (IBS has been recognized as one of the most common and best studied disorders among the group of functional gastrointestinal disorders. It is a functional bowel disorder in which abdominal pain or discomfort is associated with defecation or a change in bowel habit. In the Western world, IBS appears to affect up to 20% of the population at any given time but in Asian countries, the median value of IBS prevalence defined by various criteria ranges between 6.5% and 10.1%, and community prevalence of 4% is found in North India. Those attending gastroenterology clinics represent only the tip of the iceberg. The disorder substantially impairs the quality of life, and the overall health-care costs are high. IBS has therefore gained increased attention from clinicians, researchers, and pharmaceutical industries. It is often frustrating to both patients and physicians as the disease is usually chronic in nature and difficult to treat. However, the understanding of IBS has been changing from time to time and still most of its concepts are unknown. In this review we have discussed, debated, and synthesized the evidence base, focusing on underlying mechanisms in the brain and bowel. We conclude that it is both brain and bowel mechanisms that are responsible. The clinical implication of such mechanisms is discussed.

  20. PAINFUL IRRITABLE-BOWEL-SYNDROME AND SIGMOID CONTRACTIONS

    NARCIS (Netherlands)

    RITSEMA, GH; THIJN, CJP

    Fifteen patients with abdominal pain compatible with the irritable bowel syndrome (IBS) were examined by barium enema and pressure recording. Strong circular contractions of the sigmoid colon and pressure recordings correlated with the characteristic pain in 13 of the 15 patients. In 15 control

  1. Role of alimentation in irritable bowel syndrome

    NARCIS (Netherlands)

    Dapoigny, M.; Stockbrügger, R. W.; Azpiroz, F.; Collins, S.; Coremans, G.; Müller-Lissner, S.; Oberndorff, A.; Pace, F.; Smout, A.; Vatn, M.; Whorwell, P.

    2003-01-01

    BACKGROUND: Different food items are made responsible for irritable bowel syndrome (IBS) symptoms, but the physiopathology of IBS remains unclear. AIMS: During a meeting in Nice, France, experts of the European Working Team of the IBiS Club discussed selected data regarding the relationships between

  2. Kinetics of Hydrocarbon formation in a-C:H film deposition plasmas

    International Nuclear Information System (INIS)

    De la Cal, E.; Tabares, F.L.

    1993-01-01

    The formation of C 2 and C 3 hydrocarbons during the PACVD of a-C-H films from admixtures of methane with H 2 and He has been investigated by mass spectrometry under several deposition condition. The time evolution of the observed species indicates that the formation mechanism of ethylene and acetylene are sensitive to the conditions of the wall during the growing of the film. Acetylene are sensitive to the conditions of the wall during the growing of the carburized metal. (Author)

  3. The gendered impact of Irritable Bowel Syndrome: a qualitative study of patients' experiences.

    Science.gov (United States)

    Björkman, Ida; Dellenborg, Lisen; Ringström, Gisela; Simrén, Magnus; Jakobsson Ung, Eva

    2014-06-01

    The aim of the study was to explore the impact of irritable bowel syndrome on daily life from a gender perspective. Irritable bowel syndrome is a common functional disorder, characterized by abdominal pain, diarrhoea and/or constipation. Sufferers experience negative emotions due to unpredictable symptoms and sometimes feel trivialized by healthcare professionals. The sufferers' experience of living with this disorder has never been explored from a gender perspective. A qualitative, interpretative method was used. A qualitative, hermeneutic method was applied. Interviews were conducted with 19 patients in 2011 and analysed in a constructionist gender framework. Constructionist gender theory views gender and identity as cultural constructs that develop through interplay between the individual and his/her social context and cultural norms. The main theme to emerge from the interviews was as follows: 'A normative framework of femaleness and maleness leads to suffering for persons with irritable bowel syndrome'. This consists of three interwoven themes: 'Being forced to abandon gender illusions'; 'Being forced to transcend taboos' and 'Reinforced suffering in healthcare encounters'. Men demonstrated masculinity by stressing the importance of being solid family providers while women spoke of nurturing and relational responsibilities in line with traditional notions of femininity. The experience of living with irritable bowel syndrome differs between men and women due to differing societal expectations, life situation and the everyday construction of gender identities. Gender stereotyping by healthcare professionals perpetuates rather than alleviates the suffering experienced by men and women with irritable bowel syndrome. In healthcare encounters, women risk being trivialized and men risk being overlooked due to the 'female health concern' label attached to irritable bowel syndrome. © 2013 John Wiley & Sons Ltd.

  4. Efficacy and Tolerability of Pharmacotherapy Options for the Treatment of Irritability in Autistic Children

    Directory of Open Access Journals (Sweden)

    Eiji Kirino

    2014-01-01

    Full Text Available Children with autism have a high rate of irritability and aggressive symptoms. Irritability or self-injurious behavior can result in significant harm to those affected, as well as to marked distress for their families. This paper provides a literature review regarding the efficacy and tolerability of pharmacotherapy for the treatment of irritability in autistic children. Although antipsychotics have not yet been approved for the treatment of autistic children by many countries, they are often used to reduce symptoms of behavioral problems, including irritability, aggression, hyperactivity, and panic. However, among antipsychotics, the Food and Drug Administration has approved only risperidone and aripiprazole to treat irritability in autism. Among atypical antipsychotics, olanzapine and quetiapine are limited in their use for autism spectrum disorders in children because of high incidences of weight gain and sedation. In comparison, aripiprazole and ziprasidone cause less weight gain and sedation. However, potential QTc interval prolongation with ziprasidone has been reported. Contrary to ziprasidone, no changes were evident in the QT interval in any of the trials for aripiprazole. However, head-to-head comparison studies are needed to support that aripiprazole may be a promising drug that can be used to treat irritability in autistic children. On the other hand, risperidone has the greatest amount of evidence supporting it, including randomized controlled trials; thus, its efficacy and tolerability has been established in comparison with other agents. Further studies with risperidone as a control drug are needed.

  5. Physical characteristic and irritation index of Syzigium aromaticum essential oil in O/W and W/O creams

    Science.gov (United States)

    Safriani, R.; Sugihartini, N.; Yuliani, S.

    2017-11-01

    Essential oil of Syzigium aromaticum has been formulated in O/W and W/O creams as anti-inflammatory dosage form. The purpose of this study was to evaluate the physical characteristic and irritation index of S. aromaticum essential oil in O/W and W/O creams. The creams were made by fusion method. The creams then were evaluated the physical characteristic including pH, viscosity, spreadability and adhesivity. The irritation index was obtained by irritation skin test in male rabbit. The results showed that the W/O and O/W creams have the value of pH: 6.3 and 6.27; spreadability: 3,18 and 4.17 cm2; adhesivity: 5.59 and 0.07 minutes; viscosity: 4.43 and 2.88 Pa.S, respectively. The irritation test showed that the control enhancer caused mild irritation in both of W/O and O/W creams. These findings indicated that type of cream might influence the physical characteristic and irritation index of S. aromaticum essential oil cream.

  6. Stress-Induced Visceral Pain: Toward Animal Models of Irritable-Bowel Syndrome and Associated Comorbidities

    Science.gov (United States)

    Moloney, Rachel D.; O’Mahony, Siobhain M.; Dinan, Timothy G.; Cryan, John F.

    2015-01-01

    Visceral pain is a global term used to describe pain originating from the internal organs, which is distinct from somatic pain. It is a hallmark of functional gastrointestinal disorders such as irritable-bowel syndrome (IBS). Currently, the treatment strategies targeting visceral pain are unsatisfactory, with development of novel therapeutics hindered by a lack of detailed knowledge of the underlying mechanisms. Stress has long been implicated in the pathophysiology of visceral pain in both preclinical and clinical studies. Here, we discuss the complex etiology of visceral pain reviewing our current understanding in the context of the role of stress, gender, gut microbiota alterations, and immune functioning. Furthermore, we review the role of glutamate, GABA, and epigenetic mechanisms as possible therapeutic strategies for the treatment of visceral pain for which there is an unmet medical need. Moreover, we discuss the most widely described rodent models used to model visceral pain in the preclinical setting. The theory behind, and application of, animal models is key for both the understanding of underlying mechanisms and design of future therapeutic interventions. Taken together, it is apparent that stress-induced visceral pain and its psychiatric comorbidities, as typified by IBS, has a multifaceted etiology. Moreover, treatment strategies still lag far behind when compared to other pain modalities. The development of novel, effective, and specific therapeutics for the treatment of visceral pain has never been more pertinent. PMID:25762939

  7. The Gut Hormones in Appetite Regulation

    Directory of Open Access Journals (Sweden)

    Keisuke Suzuki

    2011-01-01

    Full Text Available Obesity has received much attention worldwide in association with an increased risk of cardiovascular diseases, diabetes, and cancer. At present, bariatric surgery is the only effective treatment for obesity in which long-term weight loss is achieved in patients. By contrast, pharmacological interventions for obesity are usually followed by weight regain. Although the exact mechanisms of long-term weight loss following bariatric surgery are yet to be fully elucidated, several gut hormones have been implicated. Gut hormones play a critical role in relaying signals of nutritional and energy status from the gut to the central nervous system, in order to regulate food intake. Cholecystokinin, peptide YY, pancreatic polypeptide, glucagon-like peptide-1, and oxyntomodulin act through distinct yet synergistic mechanisms to suppress appetite, whereas ghrelin stimulates food intake. Here, we discuss the role of gut hormones in the regulation of food intake and body weight.

  8. 21 CFR 878.4830 - Absorbable surgical gut suture.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Absorbable surgical gut suture. 878.4830 Section 878.4830 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... surgical gut suture. (a) Identification. An absorbable surgical gut suture, both plain and chromic, is an...

  9. Challenges of metabolomics in human gut microbiota research.

    Science.gov (United States)

    Smirnov, Kirill S; Maier, Tanja V; Walker, Alesia; Heinzmann, Silke S; Forcisi, Sara; Martinez, Inés; Walter, Jens; Schmitt-Kopplin, Philippe

    2016-08-01

    The review highlights the role of metabolomics in studying human gut microbial metabolism. Microbial communities in our gut exert a multitude of functions with huge impact on human health and disease. Within the meta-omics discipline, gut microbiome is studied by (meta)genomics, (meta)transcriptomics, (meta)proteomics and metabolomics. The goal of metabolomics research applied to fecal samples is to perform their metabolic profiling, to quantify compounds and classes of interest, to characterize small molecules produced by gut microbes. Nuclear magnetic resonance spectroscopy and mass spectrometry are main technologies that are applied in fecal metabolomics. Metabolomics studies have been increasingly used in gut microbiota related research regarding health and disease with main focus on understanding inflammatory bowel diseases. The elucidated metabolites in this field are summarized in this review. We also addressed the main challenges of metabolomics in current and future gut microbiota research. The first challenge reflects the need of adequate analytical tools and pipelines, including sample handling, selection of appropriate equipment, and statistical evaluation to enable meaningful biological interpretation. The second challenge is related to the choice of the right animal model for studies on gut microbiota. We exemplified this using NMR spectroscopy for the investigation of cross-species comparison of fecal metabolite profiles. Finally, we present the problem of variability of human gut microbiota and metabolome that has important consequences on the concepts of personalized nutrition and medicine. Copyright © 2016 Elsevier GmbH. All rights reserved.

  10. Influence of functional food components on gut health.

    Science.gov (United States)

    Wan, Murphy L Y; Ling, K H; El-Nezami, Hani; Wang, M F

    2018-01-30

    Intestinal epithelial cells (IECs) lining the gastrointestinal tract establish a barrier between external environments and the internal milieu. An intact intestinal barrier maintains gut health and overall good health of the body by preventing from tissue injury, pathogen infection and disease development. When the intestinal barrier function is compromised, bacterial translocation can occur. Our gut microbiota also plays a fundamentally important role in health, for example, by maintaining intestinal barrier integrity, metabolism and modulating the immune system, etc. Any disruption of gut microbiota composition (also termed dysbiosis) can lead to various pathological conditions. In short, intestinal barrier and gut microbiota are two crucial factors affecting gut health. The gastrointestinal tract is a complex environment exposed to many dietary components and commensal bacteria. Dietary components are increasingly recognized to play various beneficial roles beyond basic nutrition, resulting in the development of the functional food concepts. Various dietary modifiers, including the consumption of live bacteria (probiotics) and ingestible food constituents such as prebiotics, as well as polyphenols or synbiotics (combinations of probiotics and prebiotics) are the most well characterized dietary bioactive compounds and have been demonstrated to beneficially impact the gut health and the overall well-being of the host. In this review we depict the roles of intestinal epithelium and gut microbiota in mucosal defence responses and the influence of certain functional food components on the modulation of gut health, with a particular focus on probiotics, prebiotics and polyphenols.

  11. Probiotics, Prebiotics, and Synbiotics: Gut and Beyond

    Directory of Open Access Journals (Sweden)

    Usha Vyas

    2012-01-01

    Full Text Available The human intestinal tract has been colonized by thousands of species of bacteria during the coevolution of man and microbes. Gut-borne microbes outnumber the total number of body tissue cells by a factor of ten. Recent metagenomic analysis of the human gut microbiota has revealed the presence of some 3.3 million genes, as compared to the mere 23 thousand genes present in the cells of the tissues in the entire human body. Evidence for various beneficial roles of the intestinal microbiota in human health and disease is expanding rapidly. Perturbation of the intestinal microbiota may lead to chronic diseases such as autoimmune diseases, colon cancers, gastric ulcers, cardiovascular disease, functional bowel diseases, and obesity. Restoration of the gut microbiota may be difficult to accomplish, but the use of probiotics has led to promising results in a large number of well-designed (clinical studies. Microbiomics has spurred a dramatic increase in scientific, industrial, and public interest in probiotics and prebiotics as possible agents for gut microbiota management and control. Genomics and bioinformatics tools may allow us to establish mechanistic relationships among gut microbiota, health status, and the effects of drugs in the individual. This will hopefully provide perspectives for personalized gut microbiota management.

  12. Global F-theory GUTs

    Energy Technology Data Exchange (ETDEWEB)

    Blumenhagen, Ralph; /Munich, Max Planck Inst.; Grimm, Thomas W.; /Bonn U.; Jurke, Benjamin; /Munich, Max Planck Inst.; Weigand, Timo; /SLAC

    2010-08-26

    We construct global F-theory GUT models on del Pezzo surfaces in compact Calabi-Yau fourfolds realized as complete intersections of two hypersurface constraints. The intersections of the GUT brane and the flavour branes as well as the gauge flux are described by the spectral cover construction. We consider a split S[U(4) x U(1){sub X}] spectral cover, which allows for the phenomenologically relevant Yukawa couplings and GUT breaking to the MSSM via hypercharge flux while preventing dimension-4 proton decay. General expressions for the massless spectrum, consistency conditions and a new method for the computation of curvature-induced tadpoles are presented. We also provide a geometric toolkit for further model searches in the framework of toric geometry. Finally, an explicit global model with three chiral generations and all required Yukawa couplings is defined on a Calabi-Yau fourfold which is fibered over the del Pezzo transition of the Fano threefold P{sup 4}.

  13. Global F-theory GUTs

    International Nuclear Information System (INIS)

    Blumenhagen, Ralph; Grimm, Thomas W.; Jurke, Benjamin; Weigand, Timo

    2010-01-01

    We construct global F-theory GUT models on del Pezzo surfaces in compact Calabi-Yau fourfolds realized as complete intersections of two hypersurface constraints. The intersections of the GUT brane and the flavour branes as well as the gauge flux are described by the spectral cover construction. We consider a split S[U(4)xU(1) X ] spectral cover, which allows for the phenomenologically relevant Yukawa couplings and GUT breaking to the MSSM via hypercharge flux while preventing dimension-4 proton decay. General expressions for the massless spectrum, consistency conditions and a new method for the computation of curvature-induced tadpoles are presented. We also provide a geometric toolkit for further model searches in the framework of toric geometry. Finally, an explicit global model with three chiral generations and all required Yukawa couplings is defined on a Calabi-Yau fourfold which is fibered over the del Pezzo transition of the Fano threefold P 4 [4].

  14. Gradual Changes of Gut Microbiota in Weaned Miniature Piglets

    Directory of Open Access Journals (Sweden)

    Xianghua Yan

    2016-11-01

    Full Text Available Colonization of gut microbiota in mammals during the early life is vital to host health. The miniature piglet has recently been considered as an optimal infant model. However, less is known about the development of gut microbiota in miniature piglets. Here, this study was conducted to explore how the gut microbiota develops in weaned Congjiang miniature piglets. In contrast to the relatively stabilized gut fungal community, gut bacterial community showed a marked drop in alpha diversity, accompanied by significant alterations in taxonomic compositions. The relative abundances of 24 bacterial genera significantly declined, whereas the relative abundances of 7 bacterial genera (Fibrobacter, Collinsella, Roseburia, Prevotella, Dorea, Howardella, and Blautia significantly increased with the age of weaned piglets. Fungal taxonomic analysis showed that the relative abundances of 2 genera (Kazachstania and Aureobasidium significantly decreased, whereas the relative abundances of 4 genera (Aspergillus, Cladosporium, Simplicillium, and Candida significantly increased as the piglets aged. Kazachstania telluris was the signature species predominated in gut fungal communities of weaned miniature piglets. The functional maturation of the gut bacterial community was characterized by the significantly increased digestive system, glycan biosynthesis and metabolism, and vitamin B biosynthesis as the piglets aged. These findings suggest that marked gut microbial changes in Congjiang miniature piglets may contribute to understand the potential gut microbiota development of weaned infants.

  15. Eating, Diet, and Nutrition for Irritable Bowel Syndrome

    Science.gov (United States)

    ... Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Eating, Diet, & Nutrition for Irritable Bowel Syndrome How can ... Some people with IBS have more symptoms after eating gluten, even though they do not have celiac ...

  16. Nucleotide supplementation: a randomised double-blind placebo controlled trial of IntestAidIB in people with Irritable Bowel Syndrome [ISRCTN67764449

    Directory of Open Access Journals (Sweden)

    Attree EA

    2006-06-01

    symptoms of irritable bowel above baseline and placebo level. As expected, placebo effects were high. Apart from abdominal pain and urgency to have a bowel movement, the improvements, while consistent, are modest, and were not accompanied by improvements in any of the psychological measures. We suggest that the percentage improvement over and above the placebo effect is a physiological effect of the nucleotide supplement on the gut. The mechanisms by which these effects might improve symptoms are discussed.

  17. On building superpotentials in F-GUTs

    International Nuclear Information System (INIS)

    Saidi, E. H.

    2016-01-01

    Using characters of finite group representations, we construct the fusion algebras of operators of the spectrum of F-theory grand unified theories (GUTs). These fusion relations are used in building monodromy-invariant superpotentials of the low-energy effective 4D N=1 supersymmetric GUT models

  18. Probiotics and the Gut Immune System: Indirect Regulation.

    Science.gov (United States)

    La Fata, Giorgio; Weber, Peter; Mohajeri, M Hasan

    2018-03-01

    The gastrointestinal tract (GIT) represents the largest interface between the human organism and the external environment. In the lumen and upper part of the mucus layer, this organ hosts an enormous number of microorganisms whose composition affects the functions of the epithelial barrier and the gut immune system. Consequentially, the microorganisms in the GIT influence the health status of the organism. Probiotics are living microorganisms which, in specific conditions, confer a health benefit to the host. Among others, probiotics have immunomodulatory properties that usually act directly by (a) increasing the activity of macrophages or natural killer cells, (b) modulating the secretion of immunoglobulins or cytokines, or indirectly by (c) enhancing the gut epithelial barrier, (d) altering the mucus secretion, and (e) competitive exclusion of other (pathogenic) bacteria. This review focuses on specific bacteria strains with indirect immunomodulatory properties. Particularly, we describe here the mechanisms through which specific probiotics enhance the gut epithelial barrier and modulate mucus production. Moreover, we describe the antimicrobial properties of specific bacteria strains. Recent data suggest that multiple pathologies are associated with an unbalanced gut microflora (dysbiosis). Although the cause-effect relationship between pathology and gut microflora is not yet well established, consumption of specific probiotics may represent a powerful tool to re-establish gut homeostasis and promote gut health.

  19. Xenobiotic Metabolism and Gut Microbiomes.

    Directory of Open Access Journals (Sweden)

    Anubhav Das

    Full Text Available Humans are exposed to numerous xenobiotics, a majority of which are in the form of pharmaceuticals. Apart from human enzymes, recent studies have indicated the role of the gut bacterial community (microbiome in metabolizing xenobiotics. However, little is known about the contribution of the plethora of gut microbiome in xenobiotic metabolism. The present study reports the results of analyses on xenobiotic metabolizing enzymes in various human gut microbiomes. A total of 397 available gut metagenomes from individuals of varying age groups from 8 nationalities were analyzed. Based on the diversities and abundances of the xenobiotic metabolizing enzymes, various bacterial taxa were classified into three groups, namely, least versatile, intermediately versatile and highly versatile xenobiotic metabolizers. Most interestingly, specific relationships were observed between the overall drug consumption profile and the abundance and diversity of the xenobiotic metabolizing repertoire in various geographies. The obtained differential abundance patterns of xenobiotic metabolizing enzymes and bacterial genera harboring them, suggest their links to pharmacokinetic variations among individuals. Additional analyses of a few well studied classes of drug modifying enzymes (DMEs also indicate geographic as well as age specific trends.

  20. Impacts of Gut Bacteria on Human Health and Diseases

    Science.gov (United States)

    Zhang, Yu-Jie; Li, Sha; Gan, Ren-You; Zhou, Tong; Xu, Dong-Ping; Li, Hua-Bin

    2015-01-01

    Gut bacteria are an important component of the microbiota ecosystem in the human gut, which is colonized by 1014 microbes, ten times more than the human cells. Gut bacteria play an important role in human health, such as supplying essential nutrients, synthesizing vitamin K, aiding in the digestion of cellulose, and promoting angiogenesis and enteric nerve function. However, they can also be potentially harmful due to the change of their composition when the gut ecosystem undergoes abnormal changes in the light of the use of antibiotics, illness, stress, aging, bad dietary habits, and lifestyle. Dysbiosis of the gut bacteria communities can cause many chronic diseases, such as inflammatory bowel disease, obesity, cancer, and autism. This review summarizes and discusses the roles and potential mechanisms of gut bacteria in human health and diseases. PMID:25849657

  1. Gut Pharmacomicrobiomics: the tip of an iceberg of complex interactions between drugs and gut-associated microbes

    Directory of Open Access Journals (Sweden)

    Saad Rama

    2012-11-01

    Full Text Available Abstract The influence of resident gut microbes on xenobiotic metabolism has been investigated at different levels throughout the past five decades. However, with the advance in sequencing and pyrotagging technologies, addressing the influence of microbes on xenobiotics had to evolve from assessing direct metabolic effects on toxins and botanicals by conventional culture-based techniques to elucidating the role of community composition on drugs metabolic profiles through DNA sequence-based phylogeny and metagenomics. Following the completion of the Human Genome Project, the rapid, substantial growth of the Human Microbiome Project (HMP opens new horizons for studying how microbiome compositional and functional variations affect drug action, fate, and toxicity (pharmacomicrobiomics, notably in the human gut. The HMP continues to characterize the microbial communities associated with the human gut, determine whether there is a common gut microbiome profile shared among healthy humans, and investigate the effect of its alterations on health. Here, we offer a glimpse into the known effects of the gut microbiota on xenobiotic metabolism, with emphasis on cases where microbiome variations lead to different therapeutic outcomes. We discuss a few examples representing how the microbiome interacts with human metabolic enzymes in the liver and intestine. In addition, we attempt to envisage a roadmap for the future implications of the HMP on therapeutics and personalized medicine.

  2. Metformin Alters Gut Microbiota of Healthy Mice: Implication for Its Potential Role in Gut Microbiota Homeostasis

    Directory of Open Access Journals (Sweden)

    Wei Ma

    2018-06-01

    Full Text Available In recent years, the first-line anti-diabetic drug metformin has been shown to be also useful for the treatment of other diseases like cancer. To date, few reports were about the impact of metformin on gut microbiota. To fully understand the mechanism of action of metformin in treating diseases other than diabetes, it is especially important to investigate the impact of long-term metformin treatment on the gut microbiome in non-diabetic status. In this study, we treated healthy mice with metformin for 30 days, and observed 46 significantly changed gut microbes by using the 16S rRNA-based microbiome profiling technique. We found that microbes from the Verrucomicrobiaceae and Prevotellaceae classes were enriched, while those from Lachnospiraceae and Rhodobacteraceae were depleted. We further compared the altered microbiome profile with the profiles under various disease conditions using our recently developed comparative microbiome tool known as MicroPattern. Interestingly, the treatment of diabetes patients with metformin positively correlates with colon cancer and type 1 diabetes, indicating a confounding effect on the gut microbiome in patients with diabetes. However, the treatment of healthy mice with metformin exhibits a negative correlation with multiple inflammatory diseases, indicating a protective anti-inflammatory role of metformin in non-diabetes status. This result underscores the potential effect of metformin on gut microbiome homeostasis, which may contribute to the treatment of non-diabetic diseases.

  3. Mechanisms Underlying the Analgesic Effect of Moxibustion on Visceral Pain in Irritable Bowel Syndrome: A Review

    Directory of Open Access Journals (Sweden)

    Renjia Huang

    2014-01-01

    Full Text Available Irritable bowel syndrome (IBS is a functional bowel disorder that causes recurrent abdominal (visceral pain. Epidemiological data show that the incidence rate of IBS is as high as 25%. Most of the medications may lead to tolerance, addiction and toxic side effects. Moxibustion is an important component of traditional Chinese medicine and has been used to treat IBS-like abdominal pain for several thousand years in China. As a mild treatment, moxibustion has been widely applied in clinical treatment of visceral pain in IBS. In recent years, it has played an irreplaceable role in alternative medicine. Extensive clinical studies have demonstrated that moxibustion for treatment of visceral pain is simple, convenient, and inexpensive, and it is being accepted by an increasing number of patients. There have not been many studies investigating the analgesic mechanisms of moxibustion. Studies exploring the analgesic mechanisms have mainly focused on visceral hypersensitivity, brain-gut axis neuroendocrine system, and immune system. This paper reviews the latest developments in moxibustion use for treatment of visceral pain in IBS from these perspectives. It also evaluates potential problems in relevant studies on the mechanisms of moxibustion therapy to promote the application of moxibustion in the treatment of IBS.

  4. Redefining the gut as the motor of critical illness

    OpenAIRE

    Mittal, Rohit; Coopersmith, Craig M.

    2013-01-01

    The gut is hypothesized to play a central role in the progression of sepsis and multiple organ dysfunction syndrome. Critical illness alters gut integrity by increasing epithelial apoptosis and permeability and by decreasing epithelial proliferation and mucus integrity. Additionally, toxic gut-derived lymph induces distant organ injury. Although the endogenous microflora ordinarily exist in a symbiotic relationship with the gut epithelium, severe physiologic insults alter this relationship, l...

  5. Experimental models of the gut microbiome

    NARCIS (Netherlands)

    Venema, K.; Abbeele, P. van den

    2013-01-01

    The human gut contains a diverse microbiota with large potential to influence health. Given the difficulty to access the main sites of the gut, in vitro models have been developed to dynamically monitor microbial processes at the site of metabolic activity. These models range from simple batch

  6. The gut microbiome in atherosclerotic cardiovascular disease

    DEFF Research Database (Denmark)

    Jie, Zhuye; Xia, Huihua; Zhong, Shi-Long

    2017-01-01

    The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals...... with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular...... health. Although drug treatment represents a confounding factor, ACVD status, and not current drug use, is the major distinguishing feature in this cohort. We identify common themes by comparison with gut microbiome data associated with other cardiometabolic diseases (obesity and type 2 diabetes...

  7. Putative skin-protective formulations in preventing and/or inhibiting experimentally-produced irritant and allergic contact dermatitis.

    Science.gov (United States)

    Zhai, H; Willard, P; Maibach, H I

    1999-10-01

    The effectiveness of skin protective formulations was evaluated in a previously-described in vivo human model. All formulations failed to inhibit ammonium hydroxide and urea irritation. Only paraffin wax in cetyl alcohol statistically (plauryl sulfate irritation. Paraffin wax in cetyl alcohol was quantitatively the most effective formulation. These results suggest that some formulations may provide protective effects against certain, but not all, irritants or allergens.

  8. A single exposure to photochemical smog causes airway irritation and cardiac dysrhythmia in mice

    Science.gov (United States)

    The data presented here shows that a single exposure to photochemical smog causes airway irritation and cardiac dysrhythmia in mice. Smog, which is a complex mixture of particulate matter and gaseous irritants (ozone, sulfur dioxide, reactive aldehydes), as well as components whi...

  9. Extracellular polysaccharidases synthesized by the epiphytic lichen Evernia prunastri (L.) Ach.

    Science.gov (United States)

    Yagüe, E; Orus, M I; Estevez, M P

    1984-03-01

    Evernia prunastri Ach., an epiphytic lichen growing on Quercus rotundifolia Lam., produces a β-1,4-glucanase (EC 3.2.1.4) and a polygalacturonase (EC 3.2.1.15). The activity of these polysaccharidases increases as a response to incubation of the lichen with carboxymethylcellulose or sodium polygalacturonate, respectively. This increase in activity is thought to be the result of enzyme induction because it is inhibited by both cycloheximide and 8-azaguanine. Both polysaccharide-degrading enzymes are partially secreted into the incubation media.

  10. Non-occlusive topical exposure of human skin in vitro as model for cytotoxicity testing of irritant compounds.

    Science.gov (United States)

    Lönnqvist, Susanna; Briheim, Kristina; Kratz, Gunnar

    2016-02-01

    Testing of irritant compounds has traditionally been performed on animals and human volunteers. Animal testing should always be restricted and for skin irritancy mice and rabbits hold poor predictive value for irritant potential in humans. Irritant testing on human volunteers is restricted by the duration subjects can be exposed, and by the subjectivity of interpreting the visual signs of skin irritation. We propose an irritant testing system using viable human full thickness skin with the loss of cell viability in the exposed skin area as end point measurement. Skin was exposed to sodium dodecyl sulfate (SDS) at 20% concentration by non-occluded topical exposure to establish a positive control response and subsequent test compounds were statistically compared with the 20% SDS response. Cell viability and metabolism were measured with 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The model presents correlation between increased concentration of SDS and decreased viability of cells in the exposed skin area (R(2) = 0.76). We propose the model to be used for cytotoxicity testing of irritant compounds. With fully intact barrier function, the model comprises all cells present in the skin with quantifiable end point measurement.

  11. Aging of oxygen and hydrogen plasma discharge treated a-C:H and ta-C coatings

    Science.gov (United States)

    Bachmann, Svenja; Schulze, Marcus; Morasch, Jan; Hesse, Sabine; Hussein, Laith; Krell, Lisa; Schnagl, Johann; Stark, Robert W.; Narayan, Suman

    2016-05-01

    Surface modification with gas plasma is an efficient and easy way to improve the surface energy and the tribological behavior of diamond-like carbon (DLC) coatings, e.g., in biomedical implants or as protective coatings. However, the long-term performance of the plasma treated DLC coatings is not fully clear. We thus studied the long-term stability of two kinds of DLC coatings, namely (a) hydrogenated amorphous carbon (a-C:H) and (b) tetrahedral amorphous carbon (ta-C) treated at different radio frequency (RF) power and time of oxygen (O2) and hydrogen (H2) plasma. Their surface properties, e.g. surface wettability, structure and tribological behavior, were studied at regular intervals for a period of two months using contact angle goniometer, Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), lateral force microscopy (LFM) and ball on disc apparatus. The surface energy of both the coatings decreased upon aging. The higher the RF power and time of treatment, the higher was the hydrophobicity upon aging. XPS analysis showed that the increase in hydrophobicity could be due to adsorption of unavoidable volatile organic components in the atmosphere. The H2 plasma treated ta-C was capable of rearranging its structural bonds upon aging. The nano-friction measurements by LFM showed that the coefficient of friction of plasma treated a-C:H and ta-C decreased upon aging. The results indicate that the surface properties of plasma treated a-C:H and ta-C are not stable on long-term and are influenced by the environmental conditions.

  12. Exercise, fitness, and the gut.

    Science.gov (United States)

    Cronin, Owen; Molloy, Michael G; Shanahan, Fergus

    2016-03-01

    Exercise and gut symptomatology have long been connected. The possibility that regular exercise fosters intestinal health and function has been somewhat overlooked in the scientific literature. In this review, we summarize current knowledge and discuss a selection of recent, relevant, and innovative studies, hypotheses and reviews that elucidate a complex topic. The multiorgan benefits of regular exercise are extensive. When taken in moderation, these benefits transcend improved cardio-respiratory fitness and likely reach the gut in a metabolic, immunological, neural, and microbial manner. This is applicable in both health and disease. However, further work is required to provide safe, effective recommendations on physical activity in specific gastrointestinal conditions. Challenging methodology investigating the relationship between exercise and gut health should not deter from exploring exercise in the promotion of gastrointestinal health.

  13. A Novel Prebiotic Blend Product Prevents Irritable Bowel Syndrome in Mice by Improving Gut Microbiota and Modulating Immune Response

    Directory of Open Access Journals (Sweden)

    Qian Chen

    2017-12-01

    Full Text Available Irritable bowel syndrome (IBS is the most common functional gastrointestinal disorder yet it still lacks effective prevention therapies. The aim of this study is to determine whether a novel prebiotic blend (PB composed of fructo-oligosaccharide (FOS, galactooligosaccharide (GOS, inulin and anthocyanins could be effective in preventing the development of IBS. We explored the possible mechanisms both in animal and in cells. Post-infectious IBS models in C57BL/6 mice were established and were pretreated with the PB, PB and probiotic strains 8 weeks in advance of infection. Eight weeks after infection, intestinal tissues were collected for assessing histomorphology, visceral sensitivity, barrier function, pro-inflammatory cytokines expression and proteomics analysis. Fecal samples were also collected for microbiota analysis. The pro-inflammatory cytokines expression in Caco-2 cells were evaluated after co-incubation with PB and Salmonella typhimurium 14028. The results showed that PB significantly decreased the pro-inflammatory cytokines both in infected Caco-2 cells and PI-IBS models. The loss of body weight, decreased expression of tight junction protein Occludin (OCLN, and changes of the microbiota composition induced by infections could be greatly improved by PB intervention (p < 0.05. The proteomics analysis revealed that this function was associated with Peroxisome proliferator-activated receptor (PPARγ pathway.

  14. Gut Microbiota in Cardiovascular Health and Disease

    Science.gov (United States)

    Tang, W.H. Wilson; Kitai, Takeshi; Hazen, Stanley L

    2017-01-01

    Significant interest in recent years has focused on gut microbiota-host interaction because accumulating evidence has revealed that intestinal microbiota play an important role in human health and disease, including cardiovascular diseases. Changes in the composition of gut microbiota associated with disease, referred to as dysbiosis, have been linked to pathologies such as atherosclerosis, hypertension, heart failure, chronic kidney disease, obesity and type 2 diabetes mellitus. In addition to alterations in gut microbiota composition, the metabolic potential of gut microbiota has been identified as a contributing factor in the development of diseases. Recent studies revealed that gut microbiota can elicit a variety of effects on the host. Indeed, the gut microbiome functions like an endocrine organ, generating bioactive metabolites, that can impact host physiology. Microbiota interact with the host through a number of pathways, including the trimethylamine (TMA)/ trimethylamine N-oxide (TMAO) pathway, short-chain fatty acids pathway, and primary and secondary bile acids pathways. In addition to these “metabolism dependent” pathways, metabolism independent processes are suggested to also potentially contribute to CVD pathogenesis. For example, heart failure associated splanchnic circulation congestion, bowel wall edema and impaired intestinal barrier function are thought to result in bacterial translocation, the presence of bacterial products in the systemic circulation and heightened inflammatory state. These are believed to also contribute to further progression of heart failure and atherosclerosis. The purpose of the current review is to highlight the complex interplay between microbiota, their metabolites and the development and progression of cardiovascular diseases. We will also discuss the roles of gut microbiota in normal physiology and the potential of modulating intestinal microbial inhabitants as novel therapeutic targets. PMID:28360349

  15. How Probiotic Reduce Symptoms of Irritable Bowel Syndrome?

    Directory of Open Access Journals (Sweden)

    M Khalesi

    2014-04-01

    Full Text Available Introduction: Irritable bowel syndrome (IBS is a common gastrointestinal disorder in children that may lead to anxiety, frequent physician visits and school absenteeism. The aim of this study is to reviewe effects of probiotic for irritable bowel syndrome.   Materials and Methods: This study review articles about probiotic for irritable bowel syndrome in pubmed and google scholar.   Results: Multiple etiologic factors were suggested for IBS, including psychosocial factors, altered gastrointestinal motility,   malfermentation of food residues and changes in the intestinal micro flora. It is reported that patients with IBS have a great homogeneity in the fecal flora with a decrease in lactobacilli, coliforms and bifidobacteria in comparison to healthy individuals. The beneficial effects of probiotics in IBS could be explained by increasing the mass of beneficial bacteria such as lactobacilli strains in the digestive tract, decreasing bacterial overgrowth in the small bowel. Recently it was also demonstrated that some lactobacilli strains may modulate intestinal pain attacks by inducing the expression of μ-opioid and cannabinoid receptors in the intestinal epithelial cells. Probiotics can also reinforce the intestinal mucosal barrier and normalize the motility of the digestive tract and its visceral sensitivity and reversing the imbalance between the pro- and anti-inflammatory cytokines so that suggested as a therapeutic option for IBS.   Conclusion: Probiotic has been suggested as a therapeutic option for IBS by modulation pathophysiologic events in these patients. Keyword: Probiotic, IBS, Children.

  16. Irritability Levels of Field and Laboratory Population of Culex pipiens Complex in Tehran to Different Groups of Insecticides

    Directory of Open Access Journals (Sweden)

    Sara Rahimi

    2016-01-01

    Full Text Available Background: The irritant effect of some insecticides can cause a proportion of mosquitoes to leave the sprayed rooms before acquiring a lethal dose, so the repeated contact al sub-lethal dose may lead to extent the resistance.Methods: Larvae and pupae of Culex pipiens complex were collected in mass from open canals of waste water in capital city Tehran and reared to obtain the first generation at laboratory. Sugar-fed 2–3 days female mosquitoes were used for the experiments and compared with laboratory strain. The irritability tests of insecticides impregnated pa­pers were measured in plastic conical exposure chambers placed which implemented at controlled conditions ac­cording  to  the  method  described  by WHO .Number of take-offs were counted during 15  minutes of exposure  time.Results: DDT had the most irritancy effect against field population of Cx. pipiens. DDT, permethrin and deltamethrin was moderately irritable against laboratory strain, whereas, addition to three previous insecticides, malathion, cyfluthrin and propoxur should be also considered as moderately irritable insecticides for field population of. Irritability level of etofenprox, fenithrothion, bendiocarb, and lambdacyhalothrin did not differ from control group.Conclusion: The irritability response of mosquitoes may have a negative impact on control measures. Periodical execution of irritability tests with insecticides that routinely used in vector control program is highly recommended.

  17. Handling stress may confound murine gut microbiota studies

    Directory of Open Access Journals (Sweden)

    Cary R. Allen-Blevins

    2017-01-01

    Full Text Available Background Accumulating evidence indicates interactions between human milk composition, particularly sugars (human milk oligosaccharides or HMO, the gut microbiota of human infants, and behavioral effects. Some HMO secreted in human milk are unable to be endogenously digested by the human infant but are able to be metabolized by certain species of gut microbiota, including Bifidobacterium longum subsp. infantis (B. infantis, a species sensitive to host stress (Bailey & Coe, 2004. Exposure to gut bacteria like B. infantisduring critical neurodevelopment windows in early life appears to have behavioral consequences; however, environmental, physical, and social stress during this period can also have behavioral and microbial consequences. While rodent models are a useful method for determining causal relationships between HMO, gut microbiota, and behavior, murine studies of gut microbiota usually employ oral gavage, a technique stressful to the mouse. Our aim was to develop a less-invasive technique for HMO administration to remove the potential confound of gavage stress. Under the hypothesis that stress affects gut microbiota, particularly B. infantis, we predicted the pups receiving a prebiotic solution in a less-invasive manner would have the highest amount of Bifidobacteria in their gut. Methods This study was designed to test two methods, active and passive, of solution administration to mice and the effects on their gut microbiome. Neonatal C57BL/6J mice housed in a specific-pathogen free facility received increasing doses of fructooligosaccharide (FOS solution or deionized, distilled water. Gastrointestinal (GI tracts were collected from five dams, six sires, and 41 pups over four time points. Seven fecal pellets from unhandled pups and two pellets from unhandled dams were also collected. Qualitative real-time polymerase chain reaction (qRT-PCR was used to quantify and compare the amount of Bifidobacterium, Bacteroides, Bacteroidetes, and

  18. Chemical profiles and pharmacological activities of Chang-Kang-Fang, a multi-herb Chinese medicinal formula, for treating irritable bowel syndrome.

    Science.gov (United States)

    Mao, Qian; Shi, Lei; Wang, Zhi-Gang; Luo, Yu-Hui; Wang, Yin-Yu; Li, Xue; Lu, Min; Ju, Jian-Min; Xu, Jin-Di; Kong, Ming; Zhou, Shan-Shan; Shen, Min-Qin; Li, Song-Lin

    2017-04-06

    Chang-Kang-Fang formula (CKF), a multi-herb traditional Chinese medicinal formula, has been clinically used for treatment of irritable bowel syndrome (IBS). The mechanisms of CKF for treating IBS and the components that are responsible for the activities were still unknown. To investigate the chemical profiles and effects of CKF on IBS model. The chemical profiles of CKF were investigated by ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF-MS/MS). On colon irritation induced rat neonates IBS model, the influence of CKF on neuropeptides, including substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and 5-hydroxytryptamine (5-HT), were measured by ELISA, and the effect on intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores. In addition, the activities of CKF against acetic acid-induced nociceptive responses and prostigmin methylsulfate triggered intestinal propulsion in mice were also evaluated. 80 components were identified or tentatively assigned from CKF, including 11 alkaloids, 20 flavanoids, 4 monoterpenoids, 9 iridoid glycoside, 9 phenylethanoid glycosides, 10 chromones, 7 organic acid, 3 coumarins, 2 triterpene and 5 other compounds. On IBS rat model, CKF was observed to reduce AWR scores and levels of SP, CGRP, VIP and 5-HT. Moreover, CKF reduced the acetic acid-induced writhing scores at all dosages and reduced the intestinal propulsion ration at dosage of 7.5 and 15.0g/kg/d. CKF could alleviate the symptoms of IBS by modulating the brain-gut axis through increasing the production of neuropeptides such as CGRP, VIP, 5-HT and SP, releasing pain and reversing disorders of intestinal propulsion. Berberine, paeoniflorin, acteoside, flavonoids and chromones may be responsible for the multi-bioactivities of CKF. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  19. Maximal sfermion flavour violation in super-GUTs

    CERN Document Server

    AUTHOR|(CDS)2108556; Velasco-Sevilla, Liliana

    2016-01-01

    We consider supersymmetric grand unified theories with soft supersymmetry-breaking scalar masses $m_0$ specified above the GUT scale (super-GUTs) and patterns of Yukawa couplings motivated by upper limits on flavour-changing interactions beyond the Standard Model. If the scalar masses are smaller than the gaugino masses $m_{1/2}$, as is expected in no-scale models, the dominant effects of renormalization between the input scale and the GUT scale are generally expected to be those due to the gauge couplings, which are proportional to $m_{1/2}$ and generation-independent. In this case, the input scalar masses $m_0$ may violate flavour maximally, a scenario we call MaxFV, and there is no supersymmetric flavour problem. We illustrate this possibility within various specific super-GUT scenarios that are deformations of no-scale gravity.

  20. The gut microbiome in cardio-metabolic health

    DEFF Research Database (Denmark)

    Hansen, Tue Haldor; Gøbel, Rikke J; Hansen, Torben

    2015-01-01

    that the gut microbiota, as an environmental factor influencing the metabolic state of the host, is readily modifiable through a variety of interventions. In this review we provide an overview of the development of the gut microbiome and its compositional and functional changes in relation to cardio......With the prevalence of cardio-metabolic disorders reaching pandemic proportions, the search for modifiable causative factors has intensified. One such potential factor is the vast microbial community inhabiting the human gastrointestinal tract, the gut microbiota. For the past decade evidence has...... accumulated showing the association of distinct changes in gut microbiota composition and function with obesity, type 2 diabetes and cardiovascular disease. Although causality in humans and the pathophysiological mechanisms involved have yet to be decisively established, several studies have demonstrated...