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Sample records for irritants

  1. [Irritable colon].

    PubMed

    Madsen, J R

    2001-08-20

    Irritable bowel syndrome is a chronic, relapsing functional bowel disorder of unknown aetiology. Methods of studying intestinal motor function, nociception, and interactions of the central nervous system and enteric nervous system are not applicable for clinical use. The diagnosis is therefore made on the symptoms, but it is necessary to exclude relevant organic disease. Establishment of the diagnosis, information about the disorder, elimination of foods and other factors that provoke the symptoms, and a change in life-style are sufficient in most cases. Treatment is hampered by the lack of effective treatment and the psychological aspects. The therapeutic gain of drug administration is modest and the rate of response to placebo is high. Fibre supplementation, magnesium oxide or cisapride may be tried for constipation, diphenoxylate or loperamide for diarrhoea, and low dose tricyclic antidepressants or serotonin reuptake blockers for severe pain. The introduction of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists seems promising. PMID:11530562

  2. Irritant Contact Dermatitis

    MedlinePlus

    ... and rashes clinical tools newsletter | contact Share | Irritant Contact Dermatitis Information for adults A A A This ... severe involvement in the patient's armpit. Overview Irritant contact dermatitis is an inflammatory rash caused by direct ...

  3. Irritable bowel syndrome - aftercare

    MedlinePlus

    Irritable bowel syndrome (IBS) may be a lifelong condition. You may be suffering from cramping and loose stools, diarrhea, ... Ferri FF. Irritable bowel syndrome. In: Ferri FF, ed. Ferri's ... . Philadelphia, PA: Elsevier Mosby; 2015:pages 669-70. What I ...

  4. Professors' Irritating Behavior Study

    ERIC Educational Resources Information Center

    Malikow, Max

    2007-01-01

    The purpose of this study was to quantify the irritating behaviors of professors as experienced and reported by 232 Le Moyne College students. In this study, "irritating behavior" was understood as "actions that vex, annoy, bother, pester, frustrate, or provoke anger." The survey used in this study was developed by Larry M. Ludewig, Ph.D.,…

  5. Understanding irritant napkin dermatitis.

    PubMed

    Atherton, David J

    2016-07-01

    Irritant napkin dermatitis (IND, often referred to as irritant diaper dermatitis) is an exceedingly common problem in the first 2 years of life. It is now established that a number of factors are considered important in the etiology of IND. The principal irritants are fecal enzymes, which damage infant skin and are further amplified by a number of factors, including skin maceration and friction, high pH, the presence of urine, and the duration of contact with feces. In recent years, the decreasing incidence and severity of IND reflects improvements in the design and performance of diapers, diaper skin care products, and overall awareness about maintaining infant skin health. PMID:27311779

  6. Irritants and corrosives.

    PubMed

    Tovar, Richard; Leikin, Jerrold B

    2015-02-01

    This article reviews toxic chemicals that cause irritation and damage to single and multiple organ systems (corrosion) in an acute fashion. An irritant toxic chemical causes reversible damage to skin or other organ system, whereas a corrosive agent produces irreversible damage, namely, visible necrosis into integumentary layers, following application of a substance for up to 4 hours. Corrosive reactions can cause coagulation or liquefaction necrosis. Damaged areas are typified by ulcers, bleeding, bloody scabs, and eventual discoloration caused by blanching of the skin, complete areas of alopecia, and scars. Histopathology should be considered to evaluate questionable lesions. PMID:25455665

  7. Irritants in cigarette smoke plumes

    SciTech Connect

    Ayer, H.E.; Yeager, D.W.

    1982-11-01

    Concentrations of the irritants formaldehyde and acrolein in side stream cigarette smoke plumes are up to three orders of magnitude above occupational limits, readily accounting for eye and nasal irritation. ''Low-tar'' cigarettes appear at least as irritating as other cigarettes. More than half the irritant is associated with the particulate phase of the smoke, permitting deposition throughout the entire respiratory tract and raising the issue of whether formaldehyde in smoke is associated with bronchial cancer.

  8. Irritant-induced airway disorders.

    PubMed

    Brooks, Stuart M; Bernstein, I Leonard

    2011-11-01

    Thousands of persons experience accidental high-level irritant exposures each year but most recover and few die. Irritants function differently than allergens because their actions proceed nonspecifically and by nonimmunologic mechanisms. For some individuals, the consequence of a single massive exposure to an irritant, gas, vapor or fume is persistent airway hyperresponsiveness and the clinical picture of asthma, referred to as reactive airways dysfunction syndrome (RADS). Repeated irritant exposures may lead to chronic cough and continual airway hyperresponsiveness. Cases of asthma attributed to repeated irritant-exposures may be the result of genetic and/or host factors. PMID:21978855

  9. [Irritable colon and constipation].

    PubMed

    Meyenberger, C

    1993-04-20

    Irritable bowel syndrome is a very common clinical problem with a broad spectrum of severity. The management includes a combination of positive diagnosis of typical symptoms with limited investigations to exclude underlying structural or biochemical disorders. Therapeutic trials focus on the relief of predominant symptoms. Identification and modification of factors exacerbating symptoms, behavioural techniques and pharmacologic agents directed to the presumed gastrointestinal motor dysfunction are required. Psychological support by the physician is the most important part of treatment. Chronic constipation may be the predominant symptom of irritable bowel syndrome. Underlying organic disorders must be excluded by clinical examination and endoscopy. Severe chronic constipation requires further investigation of colonic motility and defecation. High fibre diet, osmotic laxatives and procinetic agents may lead to an improvement. In rare cases surgery may be indicated. PMID:8488351

  10. Chemosensory irritation and the lung.

    PubMed

    Nowak, Dennis

    2002-06-01

    Airway irritation involves a variety of reflex mechanisms. Tracheal and bronchial C fibres and rapidly adapting fibres mediate cough, bronchoconstriction, and mucosal vasodilation. Workplace respiratory irritants can have a variety of effects in relation to asthma. Very high exposures can cause new-onset asthma, clinically presenting as reactive airways dysfunction syndrome or irritant-induced asthma. Symptoms after exposure to irritants depend on aggregate characteristics, water solubility and dose. Measurement of pulmonary function in response to irritants includes baseline spirometry, monitoring of across-shift changes and changes in non-specific bronchial responsiveness as well as bronchial responsiveness to inhaled allergens. Following irritant exposure, inflammatory changes within the airways are monitored by bronchoalveolar lavage or - less invasively - by sputum markers. A completely non-invasive approach not limited in repeatability is the investigation of inflammatory markers in exhaled air. However, the diagnostic and prognostic values of these novel markers have still to be demonstrated. PMID:11981671

  11. Menthol attenuates respiratory irritation responses to multiple cigarette smoke irritants

    PubMed Central

    Willis, Daniel N.; Liu, Boyi; Ha, Michael A.; Jordt, Sven-Eric; Morris, John B.

    2011-01-01

    Menthol, the cooling agent in peppermint, is added to almost all commercially available cigarettes. Menthol stimulates olfactory sensations, and interacts with transient receptor potential melastatin 8 (TRPM8) ion channels in cold-sensitive sensory neurons, and transient receptor potential ankyrin 1 (TRPA1), an irritant-sensing channel. It is highly controversial whether menthol in cigarette smoke exerts pharmacological actions affecting smoking behavior. Using plethysmography, we investigated the effects of menthol on the respiratory sensory irritation response in mice elicited by smoke irritants (acrolein, acetic acid, and cyclohexanone). Menthol, at a concentration (16 ppm) lower than in smoke of mentholated cigarettes, immediately abolished the irritation response to acrolein, an agonist of TRPA1, as did eucalyptol (460 ppm), another TRPM8 agonist. Menthol's effects were reversed by a TRPM8 antagonist, AMTB. Menthol's effects were not specific to acrolein, as menthol also attenuated irritation responses to acetic acid, and cyclohexanone, an agonist of the capsaicin receptor, TRPV1. Menthol was efficiently absorbed in the respiratory tract, reaching local concentrations sufficient for activation of sensory TRP channels. These experiments demonstrate that menthol and eucalyptol, through activation of TRPM8, act as potent counterirritants against a broad spectrum of smoke constituents. Through suppression of respiratory irritation, menthol may facilitate smoke inhalation and promote nicotine addiction and smoking-related morbidities.— Willis, D. N., Liu, B., Ha, M. A., Jordt, S.-E., Morris, J. B. Menthol attenuates respiratory irritation responses to multiple cigarette smoke irritants. PMID:21903934

  12. Irritable bowel syndrome.

    PubMed

    Beck, E; Hurwitz, B

    1992-12-01

    1. Irritable bowel syndrome is a functional disorder of the lower intestinal tract affecting approximately 10% of the population and causing a wide range of symptoms. 2. Most cases of irritable bowel syndrome can be diagnosed in general practice on the basis of the presenting history and clinical examination but some patients may need to be referred to a gastro-enterologist for further assessment including sigmoidoscopy and barium enema. 3. The clinical picture may include symptoms of abdominal pain and/or distension and altered bowel habit. Nausea, dyspepsia, gynaecological or bladder symptoms are also common. About a third of patients may give a family history of recurrent abdominal pain. 4. Clinical signs include general anxiety, scars on the abdomen (from previous laparotomies for severe abdominal pain), a palpable and tender left colon or generalized abdominal tenderness, and loud borborygmi. 5. Absolute indications for a specialist assessment are: weight loss rectal bleeding onset of symptoms after the age of 40 a mass. Even in the absence of any of these findings referral is frequently necessary to allay patient anxiety and reinforce the diagnosis. 6. Blood tests are usually non-contributory. Stool specimens should be sent if diarrhoea is a feature. 7. A full explanation emphasizing the benign and often recurrent nature of the condition should be given to help patients understand the nature of their symptoms. Only after review of lifestyle and advice about diet have been provided should drug therapy be tried. PMID:1345152

  13. Menthol attenuates respiratory irritation responses to multiple cigarette smoke irritants.

    PubMed

    Willis, Daniel N; Liu, Boyi; Ha, Michael A; Jordt, Sven-Eric; Morris, John B

    2011-12-01

    Menthol, the cooling agent in peppermint, is added to almost all commercially available cigarettes. Menthol stimulates olfactory sensations, and interacts with transient receptor potential melastatin 8 (TRPM8) ion channels in cold-sensitive sensory neurons, and transient receptor potential ankyrin 1 (TRPA1), an irritant-sensing channel. It is highly controversial whether menthol in cigarette smoke exerts pharmacological actions affecting smoking behavior. Using plethysmography, we investigated the effects of menthol on the respiratory sensory irritation response in mice elicited by smoke irritants (acrolein, acetic acid, and cyclohexanone). Menthol, at a concentration (16 ppm) lower than in smoke of mentholated cigarettes, immediately abolished the irritation response to acrolein, an agonist of TRPA1, as did eucalyptol (460 ppm), another TRPM8 agonist. Menthol's effects were reversed by a TRPM8 antagonist, AMTB. Menthol's effects were not specific to acrolein, as menthol also attenuated irritation responses to acetic acid, and cyclohexanone, an agonist of the capsaicin receptor, TRPV1. Menthol was efficiently absorbed in the respiratory tract, reaching local concentrations sufficient for activation of sensory TRP channels. These experiments demonstrate that menthol and eucalyptol, through activation of TRPM8, act as potent counterirritants against a broad spectrum of smoke constituents. Through suppression of respiratory irritation, menthol may facilitate smoke inhalation and promote nicotine addiction and smoking-related morbidities. PMID:21903934

  14. Workplace respiratory irritants and asthma.

    PubMed

    Tarlo, S M

    2000-01-01

    Workplace respiratory irritants can have a variety of effects in relation to asthma. Very high exposures can cause new-onset asthma (reactive airways dysfunction syndrome or irritant-induced asthma) with or without concurrent sensitization, e.g., to diisocyanate. Aggravation of underlying asthma can result from moderate exposures. Adjuvant or other effects enhancing the risk of sensitization to high molecular weight allergens have occurred with chronic low-moderate exposures. Enhancement of airway responsiveness on a short-term basis can be produced by ozone and biological irritants such as endotoxin and beta 1-3 glucans. Production of nonasthmatic responses such as hyperventilation and vocal cord dysfunction can mimic asthma symptoms. Controversy exists as to whether moderate irritant exposures can cause asthma or long-term worsening of underlying asthma. PMID:10769351

  15. Irritable bowel syndrome.

    PubMed

    Enck, Paul; Aziz, Qasim; Barbara, Giovanni; Farmer, Adam D; Fukudo, Shin; Mayer, Emeran A; Niesler, Beate; Quigley, Eamonn M M; Rajilić-Stojanović, Mirjana; Schemann, Michael; Schwille-Kiuntke, Juliane; Simren, Magnus; Zipfel, Stephan; Spiller, Robin C

    2016-01-01

    Irritable bowel syndrome (IBS) is a functional gastrointestinal disease with a high population prevalence. The disorder can be debilitating in some patients, whereas others may have mild or moderate symptoms. The most important single risk factors are female sex, younger age and preceding gastrointestinal infections. Clinical symptoms of IBS include abdominal pain or discomfort, stool irregularities and bloating, as well as other somatic, visceral and psychiatric comorbidities. Currently, the diagnosis of IBS is based on symptoms and the exclusion of other organic diseases, and therapy includes drug treatment of the predominant symptoms, nutrition and psychotherapy. Although the underlying pathogenesis is far from understood, aetiological factors include increased epithelial hyperpermeability, dysbiosis, inflammation, visceral hypersensitivity, epigenetics and genetics, and altered brain-gut interactions. IBS considerably affects quality of life and imposes a profound burden on patients, physicians and the health-care system. The past decade has seen remarkable progress in our understanding of functional bowel disorders such as IBS that will be summarized in this Primer. PMID:27159638

  16. Irritable bowel syndrome

    PubMed Central

    Enck, Paul; Aziz, Qasim; Barbara, Giovanni; Farmer, Adam D.; Fukudo, Shin; Mayer, Emeran A.; Niesler, Beate; Quigley, Eamonn M. M.; Rajilić-Stojanović, Mirjana; Schemann, Michael; Schwille-Kiuntke, Juliane; Simren, Magnus; Zipfel, Stephan; Spiller, Robin C.

    2016-01-01

    Irritable bowel syndrome (IBS) is a functional gastrointestinal disease with a high population prevalence. The disorder can be debilitating in some patients, whereas others may have mild or moderate symptoms. The most important single risk factors are female sex, younger age and preceding gastrointestinal infections. Clinical symptoms of IBS include abdominal pain or discomfort, stool irregularities and bloating, as well as other somatic, visceral and psychiatric comorbidities. Currently, the diagnosis of IBS is based on symptoms and the exclusion of other organic diseases, and therapy includes drug treatment of the predominant symptoms, nutrition and psychotherapy. Although the underlying pathogenesis is far from understood, aetiological factors include increased epithelial hyperpermeability, dysbiosis, inflammation, visceral hypersensitivity, epigenetics and genetics, and altered brain–gut interactions. IBS considerably affects quality of life and imposes a profound burden on patients, physicians and the health-care system. The past decade has seen remarkable progress in our understanding of functional bowel disorders such as IBS that will be summarized in this Primer. PMID:27159638

  17. Postinfectious irritable bowel syndrome.

    PubMed

    Barbara, Giovanni; Cremon, Cesare; Pallotti, Francesca; De Giorgio, Roberto; Stanghellini, Vincenzo; Corinaldesi, Roberto

    2009-04-01

    Irritable bowel syndrome (IBS) is a gastrointestinal disorder characterized by abdominal pain and changes in bowel habits, not sustained by structural changes. There is now consistent evidence indicating that IBS may be the adverse outcome of an acute episode of infectious gastroenteritis, the so-called postinfectious (PI) IBS. The infectious agents involved in the development of PI-IBS include pathogenic bacteria, parasites, and viruses. Abdominal pain and diarrhea are the most common symptoms of PI-IBS. Several studies identified a number of risk factors increasing the susceptibility for PI-IBS development. These include the virulence of the pathogen, the severity, and duration of the acute enteritis, younger age, female sex, and psychological disturbances. Several mucosal abnormalities in the colon or ileum of patients who develop PI-IBS have been described. These changes include increased mucosal permeability, an increased amount of intraepithelial lymphocytes, lamina propria T cells, and mast cells, as well as serotonin-containing enteroendocrine cells. The mediators released by these activated cells may evoke enteric nervous system responses, excite sensory afferent pathways, and induce visceral hyperalgesia. Little is known about the prognosis of PI-IBS, although it is likely better than that of nonspecific IBS. There is little evidence about a specific treatment for PI-IBS. Although probiotics and antibiotics may be promising in the prevention of PI-IBS, the efficacy of these treatments should be assessed in an ad hoc designed study. PMID:19300138

  18. Irritable bowel syndrome

    PubMed Central

    2010-01-01

    Introduction The prevalence of irritable bowel syndrome (IBS) varies depending on the criteria used to diagnose it, but it ranges from about 5% to 20%. IBS is associated with abnormal gastrointestinal motor function and enhanced visceral perception, as well as psychosocial and genetic factors. People with IBS often have other bodily and psychiatric symptoms, and have an increased likelihood of having unnecessary surgery compared with people without IBS. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments in people with IBS? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 18 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: 5HT3 receptor antagonists (alosetron and ramosetron); 5HT4 receptor agonists (tegaserod); antidepressants (tricyclic antidepressants and selective serotonin reuptake inhibitors [SSRIs]); antispasmodics (including peppermint oil); cognitive behavioural therapy (CBT); hypnotherapy; soluble and insoluble fibre supplementation; and loperamide. PMID:21718578

  19. Irritable bowel syndrome

    PubMed Central

    2012-01-01

    Introduction The prevalence of irritable bowel syndrome (IBS) varies depending on the criteria used to diagnose it, but it ranges from about 5% to 20%. IBS is associated with abnormal gastrointestinal motor function and enhanced visceral perception, as well as psychosocial and genetic factors. People with IBS often have other bodily and psychiatric symptoms, and have an increased likelihood of having unnecessary surgery compared with people without IBS. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments in people with IBS? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 27 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: 5HT3 receptor antagonists (alosetron and ramosetron), 5HT4 receptor agonists (tegaserod), antidepressants (tricyclic antidepressants and selective serotonin reuptake inhibitors [SSRIs]), antispasmodics (including peppermint oil), cognitive behavioural therapy (CBT), hypnotherapy, loperamide, and soluble and insoluble fibre supplementation. PMID:22296841

  20. [Irritable bowel syndrome in adolescence].

    PubMed

    Shimada, A; Takano, M

    1992-11-01

    We studied seventy patients, 23 males and 47 females with irritable bowel syndrome in adolescence aged 13-19 yrs, who visited the department of psychosomatic medicine in Takano Hospital during about six year period of April, 1986-July, 1992. Takano Hospital is a coloproctological center in Kumamoto. In the clinical pattern of adolescent patients with irritable bowel syndrome the "gas" pattern was dominant (51.4%). Patients with the gas pattern have severe symptoms of flatus, fullness, rumbling sound and abdominal pain as well as bowel dysfunction, constipation and diarrhea in a classroom. Next, the diarrheal pattern occurred in 20.0%. Diarrheal patients complained of frequent bowel movements and retention feelings before attending school. Recurrent abdominal pain-like pattern was found in 7.1% patients. Clinical symptoms in the adolescent patients seem to derived from a mental tension and stress in a close classroom or before attending school. Many adolescenct patients (67.1%) with irritable bowel syndrome are embarrassed in school-maladjustment; leaving class early, late coming, a long absence, and a withdrawal. PMID:1363122

  1. [Irritable colon and psychosomatic disease].

    PubMed

    Morini, A; Mauceri, P; Pallotta, P; Pelliccia, G

    1984-08-25

    The authors, after having considered the close likeness between the collateral clinical picture described by others in regard to the irritable colon syndrome and the outstanding one pointed out by them in many cases of psychosomatic disorders, have analyzed again a large number of personal cases diagnosed as "psychosomatic" in order to find possible relations between these two unwholesome conditions. At the end of their examination, after having ascertained that the "Irritable colon" has not to be considered an isolated disease but a syndrome caused by many factors, hinged on a predisposing condition likely of constitutional nature, the authors remark how it may nest in the folds of a psychosomatic disorder and sometimes be its outbreaking feature. The authors by this way, don't want to conclude identifying the I.C. with a psychosomatic disorder and suggest that in such cases one may take this syndrome as the main manifestation of a condition marked by an impairment of the digestive tract motility inside a psychosomatic disorder with a somatic expression of this apparatus. PMID:6483246

  2. Irritant exposure, bronchial reactivity and asthma.

    PubMed

    Gordon, S B; Morice, A H

    1997-10-01

    The role of irritant exposure in the pathogenesis of bronchial reactivity and asthma is uncertain. This paper reviews the evidence from environmental epidemiological surveys, studies of occupationally exposed populations and chamber studies of asthmatic and nonasthmatic subjects exposed to irritant fumes. The reactive airways dysfunction syndrome and occupational asthma due to irritant exposure are considered in the context of these results. Although several irritants cause acute bronchoconstriction by a number of mechanisms in chamber studies, there is little convincing evidence to suggest that irritant exposure without pulmonary injury is a risk factor for the development of bronchial hyperresponsiveness. This is the case both in relatively intense concentrations, such as those experienced in industrial or chamber exposure, and at the levels experienced by the general population. PMID:9510667

  3. Probiotics and irritable bowel syndrome

    PubMed Central

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

    2013-01-01

    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. PMID:24106397

  4. Genetics of irritable bowel syndrome.

    PubMed

    Henström, Maria; D'Amato, Mauro

    2016-12-01

    Irritable bowel syndrome (IBS) is a common condition with a complex and largely unknown etiology. There is no cure, and treatment options are mainly directed to the amelioration of symptoms. IBS causes reduced quality of life and poses considerable repercussions on health and socioeconomic systems. There is a heritable component in IBS, and genetic research is a valuable tool for the identification of causative pathways, which will provide important insight into the pathophysiology. However, although some gene-hunting efforts have been conducted and a few risk genes proposed, IBS genetic research is lagging behind compared to other complex diseases. In this mini-review, we briefly summarize existing genetic studies, discuss the main challenges in IBS genetic research, and propose strategies to overcome these challenges for IBS gene discovery. PMID:26873717

  5. [Allergic and irritative textile dermatitis].

    PubMed

    Elsner, P

    1994-01-22

    Textile dermatitis is only one example of adverse health effects due to clothing. It may present with a wide spectrum of clinical features, but the main mechanisms are irritant dermatitis, often observed in atopics intolerant to wool and synthetic fibers, and allergic contact dermatitis, usually caused by textile finishes and dyes. The newer azo dyes Disperse Blue 106 and 124 in particular are potent sensitizers that have caused significant problems, most recently in the form of "leggins dermatitis". Although severe textile dermatitis appears to be a rare event, more systematic population-based research is needed since many oligosymptomatic cases are probably overlooked. Criteria for healthy textiles are an optimum combination of efficacy (regulation of skin temperature and humidity and protection from environmental damage) and safety (lack of carcinogenicity, toxicity and allergenicity). If potentially allergenic substances are used in textiles, they should be declared as in the case of cosmetics. PMID:8115841

  6. Evaulation of irritation potential of surfactant mixtures.

    PubMed

    Turkoglu, M; Sakr, A

    1999-12-01

    Irritation potential of sodium laureth sulfate (SLES) alone, and in combination with lauryl glucoside (LG), polysorbate 20 (PS) and cocoamidopropyl betaine (CAPB) was tested in 13 human subjects. Four main and six sub-formulations were prepared and evaluated. Formulations were applied to the forearm as a 24 h close patch study. Irritation was scored by two different methods using an in vivo clinical protocol based on visual scoring and on the stratum corneum capacitance measurement. Irritation was found to be dose dependent. At 2 mg/patch level ten subjects did not show any skin reaction. At 20 mg/patch level eleven subjects showed a broad range of skin irritation. The highest irritation was observed with the formula that contained SLES, LG, and cocamide DEA together. Among the sub-formulations, cocamide DEA showed the highest irritation grade. A statistically significant correlation was observed between visual, clinical and corneometer scores. It was concluded that the irritation potential of surfactants was related to the total surfactant concentration, application mode, and the thermodynamic activity of molecules in the solution as well as the chemical structure of the surfactant molecules. PMID:18503452

  7. Irritability in Pediatric Patients: Normal or Not?

    PubMed Central

    Hameed, Usman; Dellasega, Cheryl A.

    2016-01-01

    The goal of this article is to describe the concept of irritability in children and youth, which has been revisited in the DSM-5. Traditionally, this behavior has been more commonly associated with mood disorders, which may account for the rising incidence of bipolar disorder diagnosis and overuse of mood-stabilizing medications in pediatric patients. While not predictive of mania, persistent nonepisodic irritability, if undetected, may escalate to violent behavior with potentially serious outcomes. It is therefore important to educate clinicians about how to accurately assess irritability in pediatric patients. PMID:27486529

  8. Irritant-induced asthma in the workplace.

    PubMed

    Tarlo, Susan M

    2014-01-01

    Irritant-induced asthma in the workplace has been the focus of several articles in the past few years, and reviewed here. A clinical case definition is most readily associated with a single acute/accidental exposure to a presumed high concentration of an agent or agents expected to be irritant to the airways, as was initially reported with the subgroup Reactive Airways Dysfunction Syndrome (RADS). When most but not all criteria for RADS are met, then a diagnosis of irritant-induced asthma may also be considered to be "more probable than not". However, in addition, there is evolving understanding from epidemiological studies that chronic exposures may be associated with an increased risk of developing asthma. Despite this recognition, the mechanisms and clinical case definitions of work-related asthma that might be caused by chronic exposures to irritants (vs. new-onset asthma that begins coincidentally to work exposures), remain unclear at present. PMID:24343122

  9. [Parasitosis and irritable bowel syndrome].

    PubMed

    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. PMID:27598274

  10. Focus on irritable bowel syndrome.

    PubMed

    Scalera, A; Loguercio, C

    2012-09-01

    The Irritable bowel syndrome (IBS) is a clinical syndrome characterized by chronic abdominal dis-comfort associated with changes in bowel habits and these symptoms can't be explained by any biochemical or organic abnormalities. The review summarizes the relevant findings that have emerged in recent years on the pathogenesis of this syndrome. The most important mechanisms recently implicated in the genesis of IBS symptoms are the abnormal intestinal motility, the incongruous intestinal gas production and the enhanced intestinal nociception. A lot evidence confirms the presence of dysfunction of the intrinsic enteric nervous system (ENS) as demonstrated by the presence of altered expression of transient receptor potential vanilloid 1 (TRPV1), acid sensing ion channel 3 (ASIC3), putinergic receptor P2X, ligand-gated ion channel 3 (P2X3r), tetrodoxin-sensitive receptor 2 (TTRX2), protease activated receptors (PPARs) and others. There are different assumption that explain these phenomena, and the impairment of the immune system is one of the most reliable. In IBS subjects it was found that the immune system is altered in both the cellular composition and its activation. Many studies have shown that inflammation and immune dysregulation affect the sensitivity of nerve fibers so it is vital to build on this argument for the development of effective therapies to control the symptoms of this syndrome. PMID:23047498

  11. Irritable bowel syndrome: aeromedical considerations.

    PubMed

    Rayman, Russell B

    2011-11-01

    Irritable bowel syndrome (IBS) is a gastrointestinal disorder diagnosed in accordance with the Rome III criteria. The pathophysiology of this illness is not well defined and there are no known structural abnormalities, biomedical markers, nor inflammatory causes to explain the symptoms. There are a number of serious illnesses, such as colon cancer, ulcerative colitis, and celiac disease that mimic IBS. If the Rome III criteria are satisfied and there are no alarm features of more serious illness, an in-depth workup is not necessary. There are numerous treatment regimens for IBS, none of which are curative nor offer universal relief. Some of the treatment regimens, such as antispasmodics and antidiarrheals, are not suitable for aviators because of anticholinergic effects and sedation. The aeromedical disposition decision is always challenging because of the vagaries of this illness. In general, a more liberal policy for pilots in civil aviation would be in order as long as symptoms are not frequent nor severe and not requiring antispasmodics or antidiarrheals while flying. A more conservative policy is in order for military pilots, possibly requiring restriction to multiseat aircraft. PMID:22097642

  12. Management of irritable bowel syndrome.

    PubMed

    Torii, Akira; Toda, Gotaro

    2004-05-01

    Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders. The prevalence rate is 10-20% and women have a higher prevalence. IBS adversely affects quality of life and is associated with health care use and costs. IBS comprises a group of functional bowel disorders in which abdominal discomfort or pain is associated with defecation or a change in bowel habit, and with features of disordered defecation. The consensus definition and criteria for IBS have been formalized in the "Rome II criteria". Food, psychiatric disorders, and gastroenteritis are risk factors for developing IBS. The mechanism in IBS involves biopsychosocial disorders; psychosocial factors, altered motility, and heightened sensory function. Brain-gut interaction is the most important in understanding the pathophysiology of IBS. Effective management requires an effective physician-patient relationship. Dietary treatment, lifestyle therapy, behavioral therapy, and pharmacologic therapy play a major role in treating IBS. Calcium polycarbophil can benefit IBS patients with constipation or alternating diarrhea and constipation. PMID:15206545

  13. [Contemporary dietotherapy of the irritable bowel syndrome].

    PubMed

    Pilipenko, V I; Burliaeva, E A; Isakov, V A

    2013-01-01

    Irritable bowel syndrome (IBS) is the most prevalent functional disease of the gastrointestinal tract. This highly prevalent condition is best diagnosed by assessing the constellation of symptoms with which patients present to their physicians. Because some critics have previously questioned whether irritable bowel syndrome and other functional gastrointestinal disorders truly exist because they do not have defining structural features, the Rome Foundation fostered the use of symptom-based criteria for universal use. In most cases treatment is reduced to symptomatic therapy because a lot of unknown in pathogenesis by irritable bowel syndrome. Irritable bowel syndrome leads to decrease of quality of life of the patients and could be one of the reasons of patients' disability. Food is believed by patients promotes symptoms and the diet or avoiding specific food can reduce symptoms. Possible role of different food and microbiota in the pathophysiology of irritable bowel syndrome, as well as the data from randomized, controlled clinical trials dedicated to the effects of diet in irritable bowel syndrome are summarized and discussed in this review. The efficacy of the diet, enriched by fiber, prebiotics, probiotics, peppermint oil, curcumin and vitamin B6 in irritable bowel syndrome patients was shown in numerous studies. In some studies restriction in consumption of fermented carbohydrates, coffee and alcohol, as well as diet with elimination IgG-sensed food was also shown to be effective in irritable bowel syndrome. Food intolerances, defined as non-toxic non-immune adverse reactions to food, include reactions to bioactive chemicals in foods and metabolic reactions to poorly absorbed dietary carbohydrates. New dietary approaches like polyunsaturated fatty acids intake correction and the low tryptophan intake are discussed. PMID:23808281

  14. Irritable bowel syndrome: Is it “irritable brain” or “irritable bowel”?

    PubMed Central

    Padhy, Susanta Kumar; Sahoo, Swapnajeet; Mahajan, Sonali; Sinha, Saroj Kumar

    2015-01-01

    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. PMID:26752904

  15. Diet in irritable bowel syndrome.

    PubMed

    El-Salhy, Magdy; Gundersen, Doris

    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-coeliac gluten sensitivity (NCGS). The component in wheat that triggers symptoms in NCGS appears to be the carbohydrates. Patients with NCGS appear to be IBS patients who are self-diagnosed and self-treated with a gluten-free diet. IBS symptoms are triggered by the consumption of the poorly absorbed fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) and insoluble fibre. On reaching the distal small intestine and colon, FODMAPS and insoluble fibre increase the osmotic pressure in the large-intestine lumen and provide a substrate for bacterial fermentation, with consequent gas production, abdominal distension and abdominal pain or discomfort. Poor FODMAPS and insoluble fibres diet reduces the symptom and improve the quality of life in IBS patients. Moreover, it changes favourably the intestinal microbiota and restores the abnormalities in the gastrointestinal endocrine cells. Five gastrointestinal endocrine cell types that produce hormones regulating appetite and food intake are abnormal in IBS patients. Based on these hormonal abnormalities, one would expect that IBS patients to have increased food intake and body weight gain. However, the link between obesity and IBS is not fully studied. Individual dietary guidance for intake of poor FODMAPs and insoluble fibres diet in combination with probiotics intake and regular exercise is to be recommended for IBS patients. PMID:25880820

  16. The Brief Irritability Test (BITe): a measure of irritability for use among men and women.

    PubMed

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

    2015-02-01

    Elevated levels of irritability have been reported across a range of psychiatric and medical conditions. However, research on the causes, consequences, and treatments of irritability has been hindered by limitations in existing measurement tools. This study aimed to develop a brief, reliable, and valid self-report measure of irritability that is suitable for use among both men and women and that displays minimal overlap with related constructs. First, 63 candidate items were generated, including items from two recent irritability scales. Second, 1,116 participants (877 university students and 229 chronic pain outpatients) completed a survey containing the irritability item pool and standardized measures of related constructs. Item response theory was used to develop a five-item scale (the Brief Irritability Test) with a strong internal structure. All five items displayed minimal conceptual overlap with related constructs (e.g., depression, anger), and test scores displayed negligible gender bias. The Brief Irritability Test shows promise in helping to advance the burgeoning field of irritability research. PMID:24830513

  17. The Brief Irritability Test (BITe): A Measure of Irritability for Use Among Men and Women

    PubMed Central

    Holtzman, Susan; O’Connor, Brian P.; Barata, Paula C.; Stewart, Donna E.

    2014-01-01

    Elevated levels of irritability have been reported across a range of psychiatric and medical conditions. However, research on the causes, consequences, and treatments of irritability has been hindered by limitations in existing measurement tools. This study aimed to develop a brief, reliable, and valid self-report measure of irritability that is suitable for use among both men and women and that displays minimal overlap with related constructs. First, 63 candidate items were generated, including items from two recent irritability scales. Second, 1,116 participants (877 university students and 229 chronic pain outpatients) completed a survey containing the irritability item pool and standardized measures of related constructs. Item response theory was used to develop a five-item scale (the Brief Irritability Test) with a strong internal structure. All five items displayed minimal conceptual overlap with related constructs (e.g., depression, anger), and test scores displayed negligible gender bias. The Brief Irritability Test shows promise in helping to advance the burgeoning field of irritability research. PMID:24830513

  18. A shortened psychophysical task to quantify irritability: the Reactive Irritability Scale II (RIS-II).

    PubMed

    Faraday, Martha M; Scheufele, Peter M; Vander Ley, Kelly J; Grunberg, Neil E

    2005-02-01

    The Reactive Irritability Scale (RIS) uses magnitude estimation to measure reactive irritability. Respondents rate target sounds in comparison to a neutral reference sound. The RIS proved more sensitive than self-report measures to detect irritability associated with withdrawal from cigarette smoking and with exposure to a stressful environment, but was too long (30 min) for routine use. We report here on a shortened version (13 min)--RIS-II. The RIS-II exhibited robust test-retest reliability and correlated strongly with the original RIS (Study 1). In Study 2, the RIS-II was administered to subjects who experienced psychological stress and then were exposed to progressive relaxation, music, cognitive tasks, or silence; the Progressive Relaxation group was the most irritable. In Study 3, the RIS-II was administered to chronic pain patients. Pain patients found the sounds less irritating than did controls with the exception of the reference sound; repeated presentation of the reference sound increased irritability. These studies indicate that the RIS-II is a reliable instrument that may have utility for the measurement of irritability in laboratory and clinical settings. In addition, these studies indicate that the RIS-II is understandable by individuals of different ages who are from educationally- and culturally-diverse backgrounds and individuals who are healthy as well as individuals suffering from chronic medical conditions who are on multiple medications. PMID:15887872

  19. NEUROPEPTIDE MODULATION OF CHEMICALLY INDUCED SKIN IRRITATION

    EPA Science Inventory

    This study was designed to demonstrate that the early symptoms of chemically-induced skin irritation are neurally mediated. everal approaches were used to affect nerve transmission in adult Balb/c female mice. hese included general anesthesia (i.e., sodium pentobarbital), systemi...

  20. Definition and Facts for Irritable Bowel Syndrome

    MedlinePlus

    ... Next: Symptoms and Causes of Irritable Bowel Syndrome Digestive Disease Organizations Many organizations provide support to patients and medical professionals. View the full list of Digestive Disease Organizations​​ (PDF, 341 KB)​​​​​ Contact Us Health ...

  1. Irritable Bowel Syndrome and Female Patients.

    PubMed

    Harris, Lucinda A; Umar, Sarah B; Baffy, Noemi; Heitkemper, Margaret M

    2016-06-01

    Irritable bowel syndrome is probably the most common functional gastrointestinal disorder and is characterized by abdominal pain along with altered bowel function. It is a disorder of female predominance. This article focuses on how being female influences the pathophysiology, diagnosis, management, and treatment of this common disorder and discusses the evidence and important controversies related to these areas. PMID:27261893

  2. Acute toxicity and primary irritancy of alkylalkanolamines.

    PubMed

    Ballantyne, B; Leung, H W

    1996-12-01

    The acute handling hazards of several alkylalkanolamines were determined by investigating their potential acute toxicity and primary irritancy. Materials studied were N-methylethanolamine (MEA), N, N, -dimethylethanolamine (DMEA), N, N, -dimethylisopropanolamine (DMIPA), N-methyldiethanolamine (MDEA), and tertbutyldiethanolamine (BDEA). All these alkylalkanolamines were of comparable acute peroral toxicity in the rat (LD50 range 1.48-2.83 ml/kg). By 24 h occluded epicutaneous contact in the rabbit, MEA, DMEA and DMIPA were of moderate acute percutaneous toxicity (LD50 range 1.13-2.0 ml/kg), MDEA was of slight acute percutaneous toxicity (LD50 male 9.85 ml/kg, female 10.90 ml/kg), and BDEA of intermediate toxicity (LD50 6.4 ml/kg). Due to differences in vapor pressure the acute vapor exposure toxicity of the alkylalkanolamines to rats varied; MEA, MDEA and BDEA were of a low order of acute toxicity, and DMIPA was moderately toxic with an LT50 of 3.2 h for a saturated vapor atmosphere exposure. A 4 h-LC50 (rat combined sex) of 1461 ppm was determined for DMEA. All alkylalkanolamines studied, except MDEA, were moderately to markedly irritating and caused variable degrees of skin corrosivity; MDEA caused only transient minor skin irritation. In accord with the skin irritancy results, the eye irritancy from 0.005 ml MEA, DMEA, DMIPA and BDEA was severe, and that from MDEA was slight. Exposure to these compounds has implications for occupational health procedures. PMID:8948072

  3. [Irritant contact dermatitis. Part I. Epidemiology, etiopathogenesis and clinical manifestation].

    PubMed

    Chomiczewska, Dorota; Kieć-Swierczyńska, Marta; Krecisz, Beata

    2008-01-01

    Irritant contact dermatitis is a frequent problem in dermatology. It compromises the majority of all occupational skin diseases in most countries. It develops as a result of the environmental or work-related exposure to irritants. Cutaneous reaction depends on the intrinsic properties of the irritant, individual skin susceptibility and environmental conditions. A great morphological variety of irritant contact dermatitis and difficulties in diagnosis may lead to misdiagnosis and inadequate treatment. The prognosis is variable. Preventive measures, including education, individual skin protection and proper skin care may contribute to the reduced incidence of occupational irritant contact dermatitis. PMID:19227886

  4. Irritative symptoms and exposure to mineral wool.

    PubMed

    Petersen, R; Sabroe, S

    1991-01-01

    In a cross-sectional study undertaken in 1981 using a postal questionnaire, the prevalence of irritative symptoms was investigated among 2,654 Danish construction workers working with mineral wool. An evaluation was undertaken in a multivariate logit analysis of the relationship between exposure level (measured by hours of exposure to mineral wool per month) and prevalence of symptoms. The analysis controlled for the confounders of age, smoking habits, and exposure to organic solvents. With greater exposure to mineral wool, there was a statistically significant increase in the frequency of irritative symptoms from the eyes, the skin, and the upper respiratory tract. Among construction workers working with mineral wool 160-180 hours per month, two-thirds had these symptoms once a week or oftener. The occurrence was 2-3 times higher compared with the construction workers not working with mineral wool. The relationship between exposure to mineral wool and skin and mucous membrane symptoms may be explained by the irritative action of the fibers that are given off during insulation work. PMID:1831004

  5. Proretinal nanoparticles: stability, release, efficacy, and irritation

    PubMed Central

    Pisetpackdeekul, Pimolphan; Supmuang, Piyapan; Pan-In, Porntip; Banlunara, Wijit; Limcharoen, Benchaphorn; Kokpol, Chayada; Wanichwecharungruang, Supason

    2016-01-01

    Despite many potent biological activities, retinoids such as retinoic acid (RA) and retinal possess dose-related broad side effects. In this study, we show that this problem, which has been unsolvable for a long time, can be tackled through a controlled release strategy in which retinal is continuously delivered to the skin via sustained release from proretinal nanoparticles. The water dispersible proretinal nanoparticles are stable when kept in water at neutral pH and at room temperature for 8 months under light-proof conditions, and show sustained release of retinal into human synthetic sebum at a pH of 5. In the daily topical application tests performed for 4 weeks on rats’ skin, the nanoparticles showed superior ability to increase epidermal thickness compared to RA and retinal, with no skin irritation observed for the proretinal particles, but severe skin irritation observed for RA and free retinal. When tested under occlusion conditions in human volunteers, insignificant skin irritation was observed for the proretinal nanoparticles. The 12-week, double-blind, split-face study on human volunteers indicates better antiaging efficacy of the particles as compared to the free RA. PMID:27499622

  6. Proretinal nanoparticles: stability, release, efficacy, and irritation.

    PubMed

    Pisetpackdeekul, Pimolphan; Supmuang, Piyapan; Pan-In, Porntip; Banlunara, Wijit; Limcharoen, Benchaphorn; Kokpol, Chayada; Wanichwecharungruang, Supason

    2016-01-01

    Despite many potent biological activities, retinoids such as retinoic acid (RA) and retinal possess dose-related broad side effects. In this study, we show that this problem, which has been unsolvable for a long time, can be tackled through a controlled release strategy in which retinal is continuously delivered to the skin via sustained release from proretinal nanoparticles. The water dispersible proretinal nanoparticles are stable when kept in water at neutral pH and at room temperature for 8 months under light-proof conditions, and show sustained release of retinal into human synthetic sebum at a pH of 5. In the daily topical application tests performed for 4 weeks on rats' skin, the nanoparticles showed superior ability to increase epidermal thickness compared to RA and retinal, with no skin irritation observed for the proretinal particles, but severe skin irritation observed for RA and free retinal. When tested under occlusion conditions in human volunteers, insignificant skin irritation was observed for the proretinal nanoparticles. The 12-week, double-blind, split-face study on human volunteers indicates better antiaging efficacy of the particles as compared to the free RA. PMID:27499622

  7. Pulmonary alterations associated with inhalation of occupational and environmental irritants.

    PubMed

    Castranova, V; Frazer, D G; Manley, L K; Dey, R D

    2002-02-01

    Many gases, vapors, or particles found in occupational and/or environmental settings can act as irritants. In the present study, sensory irritants are characterized by the stimulation of neuropeptide release from sensory nerves in the nasal mucosa, while pulmonary irritants are characterized by recruitment of PMN into bronchoalveolar airspaces, elevation of breathing frequency, and neuropeptide release from sensory fibers innervating the epithelium of the conducting airways. A review of data from our laboratory as well as results from others indicate that asphalt fume is a sensory irritant; toluene diisocyanate (TDI), methyl isocyanate, and machining fluid act as both sensory and pulmonary irritants; while cotton dust, agricultural dusts, microbial products, leather conditioner, and ozone exhibit responses characteristic of pulmonary irritants. PMID:11811921

  8. TRPA1 receptors mediate environmental irritant-induced meningeal vasodilatation

    PubMed Central

    Kunkler, Phillip Edward; Ballard, Carrie Jo; Oxford, Gerry Stephen; Hurley, Joyce Harts

    2010-01-01

    The TRPA1 receptor is a member of the transient receptor potential (TRP) family of ion channels expressed in nociceptive neurons. TRPA1 receptors are targeted by pungent compounds from mustard and garlic and environmental irritants such as formaldehyde and acrolein. Ingestion or inhalation of these chemical agents causes irritation and burning in the nasal and oral mucosa and respiratory lining. Headaches have been widely reported to be induced by inhalation of environmental irritants, but it is unclear how these agents produce headache. Stimulation of trigeminal neurons releases CGRP and substance P and induces neurogenic inflammation associated with the pain of migraine. Here we test the hypothesis that activation of TRPA1 receptors are the mechanistic link between environmental irritants and peptide mediated neurogenic inflammation. Known TRPA1 agonists and environmental irritants stimulate CGRP release from dissociated rat trigeminal ganglia neurons and this release is blocked by a selective TRPA1 antagonist, HC-030031. Further, TRPA1 agonists and environmental irritants increase meningeal blood flow following intranasal administration. Prior dural application of the CGRP antagonist, CGRP8–37, or intranasal or dural administration of HC-030031, blocks the increases in blood flow elicited by environmental irritants. Together these results demonstrate that TRPA1 receptor activation by environmental irritants stimulates CGRP release and increases cerebral blood flow. We suggest that these events contribute to headache associated with environmental irritants. PMID:21075522

  9. Irritable Bowel Syndrome: A Review Article

    PubMed Central

    Vahedi, H; Ansari, R; Mir-Nasseri, MM; Jafari, E

    2010-01-01

    Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorder noted in the general population worldwide. Its chronic nature, signs and symptoms which vary periodically from mild to severe have many negative effects on the quality of life for the sufferer; therefore the appropriate treatment of these patients is highly important. Patients should be informed by their doctors that the nature of the disease is benign, and educated on how to deal with and control symptoms of the disease. This article sets out a review of recent studies on the prevalence of IBS in Iran and appropriate methods for management of patients affected by IBS. PMID:25197516

  10. Novel pharmacological therapies for irritable bowel syndrome.

    PubMed

    Corsetti, Maura; Whorwell, Peter

    2016-07-01

    Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder, which represents a major cost to healthcare services. Current pharmacological treatment includes fibre supplements, antispasmodics, laxatives, loperamide and antidepressants. This article reviews the novel pharmacological treatments already or recently approved for patients with IBS-C (lubiprostone, linaclotide) and IBS-D (alosetron, ramosetron, rifaximin, eluxadoline). Furthermore, results for drugs in development (plecanatide, ibudutant and ebastine) or used in chronic constipation or for other indications, with potential application in IBS (prucalopride, elobixibat, mesalazine, ondansetron and colesevelam) are also reviewed. PMID:26907518

  11. Butyric acid in irritable bowel syndrome.

    PubMed

    Załęski, Andrzej; Banaszkiewicz, Aleksandra; Walkowiak, Jarosław

    2013-01-01

    Butyric acid (butanoic acid) belongs to a group of short-chain fatty acids and is thought to play several beneficial roles in the gastrointestinal tract. Butyric anion is easily absorbed by enteric cells and used as a main source of energy. Moreover, butyric acid is an important regulator of colonocyte proliferation and apoptosis, gastrointestinal tract motility and bacterial microflora composition in addition to its involvement in many other processes including immunoregulation and anti-inflammatory activity. The pathogenesis of irritable bowel syndrome (IBS), the most commonly diagnosed functional gastrointestinal condition, is complex, and its precise mechanisms are still unclear. This article describes the potential benefits of butyric acid in IBS. PMID:24868283

  12. Butyric acid in irritable bowel syndrome

    PubMed Central

    Załęski, Andrzej; Walkowiak, Jarosław

    2013-01-01

    Butyric acid (butanoic acid) belongs to a group of short-chain fatty acids and is thought to play several beneficial roles in the gastrointestinal tract. Butyric anion is easily absorbed by enteric cells and used as a main source of energy. Moreover, butyric acid is an important regulator of colonocyte proliferation and apoptosis, gastrointestinal tract motility and bacterial microflora composition in addition to its involvement in many other processes including immunoregulation and anti-inflammatory activity. The pathogenesis of irritable bowel syndrome (IBS), the most commonly diagnosed functional gastrointestinal condition, is complex, and its precise mechanisms are still unclear. This article describes the potential benefits of butyric acid in IBS. PMID:24868283

  13. The effect of damaged skin barrier induced by subclinical irritation on the sequential irritant contact dermatitis.

    PubMed

    Yan-yu, Wu; Xue-min, Wang; Yi-Mei, Tan; Ying, Cheng; Na, Liu

    2011-12-01

    Skin damage caused by a single specific stimulus has been extensively studied. However, many additional mild skin irritants are experienced every day before obvious irritant contact dermatitis (ICD) appears. The effect that these previously experienced mild irritations have on the incidence and severity of sequential ICD remains undefined. The purpose of this work was to explore whether the effects of skin barrier damage induced by either the open patch test with 1% sodium lauryl sulfate (SLS), tape stripping test (TAP) (10×), or irradiation with 0.75 median erythemal dose UVB (MED) will affect the severity of sequential irritant dermatitis induced by a 0.5% SLS occlusive patch test (PT). Nine treatments were applied to nine different locations of the ventral forearm of each subject at random. The nine treatment types were as follows: open patch test with 1% SLS; 10× TAP; UVB irradiation with 0.75 MED; open patch test with 1% SLS + PT with 0.5% SLS (SLSPT); 10× TAP + PT with 0.5% SLS (TAPPT); UVB irradiation with 0.75 MED + PT with 0.5% SLS (UVPT); PT with distilled water (DISPT); PT with 0.5% SLS (PT); and the CONTROL (no treatment). After 5 days of subclinical irritation, the PT was applied on day 6. Transepidermal water loss (TEWL), capacitance (CAP), and skin color (a*) were measured at baseline and on days 6, 7, and 8. After the PT, indices of irritancy of PT, UVPT, SLSPT, and TAPPT were 60, 80, 87 and 100%, respectively. The index of irritancy of TAPPT and SLSPT were significantly higher than that of PT (p < 0.05). Clinical scores of SLSPT and TAPPT were also significantly higher than PT (p < 0.05). After 5 days of irritation, TEWL of SLS, TAP, SLSPT, and TAPPT were increased significantly compared to that of baseline. After the PT, D-value of TEWL between day 8 and day 6 ((≥6-8)TEWL) of SLSPT and TAPPT were greater than that of PT, and D-value of TEWL between day 8 and day 7 ((≥7-8)TEWL) of SLSPT and TAPPT were less than that of PT values. After the

  14. [Irritable bowel syndrome: a functional disorder?].

    PubMed

    Man, Fernando; Bustos Fernández, Luis María

    2013-12-01

    Irritable bowel syndrome is a highly prevalent condition responsible for almost one third of visits to the gastroenterologist and huge expenses for diagnosis, treatment and loss of working days. A unique pathophysiologic mechanism has not been elucidated yet and several possibilities have been proposed such as senso-perception and motor disturbances, the effect of stress and anxiety, serotonin receptor failures, activation of abnormal brain areas and pain modulation differences, among others. The absence of a biological marker has led the investigators to consider this syndrome as an exclusion diagnostic condition, once the organic diseases have been discarded The changes in gut microbiota have recently raised great interest among gastroenterologists. The study of the small intestinal bowel overgrowth syndrome, the effect of antibiotics upon the flora, the recognition of post-infectious irritable bowel syndrome and the action of probiotics, together with the effect of malabsortion of diet carbohydrates have brought some new light in our knowledge. The present update will focus on the published evidence about the subject, bearing in mind that the mechanisms elicited here are only suitable for a subgroup of patients. PMID:24516961

  15. In vitro alternatives for ocular irritation.

    PubMed Central

    Curren, R D; Harbell, J W

    1998-01-01

    The necessity of using animals to test whether new chemicals and products are eye irritants has been questioned with increasing frequency and fervor over the last 20 years. During this time many new nonanimal methods have been proposed as reliable alternatives to the traditional rabbit (Draize) test. To date, however, none of these nonanimal (in vitro) tests have become universally accepted as a complete replacement for the Draize test. To understand why a complete replacement has not been found, one has to first understand the reasonably complex structure of the eye, the standard Draize scoring scale--which is based on a qualitative evaluation of three different tissues--the differences between human and rabbit eyes, the intrinsic variability of the animal test, and the details of the different in vitro tests that have been proposed as replacements. The in vitro tests vary from relatively simple assays using single cells to more sophisticated assays that use discarded animal tissue or artificially constructed human tissue. It is clear that appropriately designed in vitro tests will eventually give more useful mechanistic information about ocular injury from which we can more comfortably predict the risk of human eye irritation from new products and ingredients. Images Figure 1 Figure 2 PMID:9599696

  16. [Neonatal parechovirus infection, fever, irritability and myositis].

    PubMed

    Eyssette-Guerreau, S; Boize, P; Thibault, M; Sarda, H

    2013-07-01

    Human parechovirus (HPeV) is associated with central nervous system infection and sepsis-like illness in newborn infants. The most frequent signs are fever, seizures, irritability, rash, and encephalitis. We report 4 cases of full-term infants with HPeV infection. They were admitted from home to the pediatric emergency unit of our hospital in October 2012. The median age at onset of symptoms was 15 days. They all developed sepsis-like illness with predominantly gastrointestinal disease and irritability. Two patients developed respiratory problems and 2 a skin rash (concerning only the extremities for one). Two patients required hospitalization in an intensive care unit. There was normal or mild inflammatory syndrome, normal white blood cell or mild leukopenia, hepatitis. We describe for the first time elevation of muscular enzymes in 3 of these patients. The diagnosis of HPeV infection was made by positive HPeV real-time PCR in cerebrospinal fluid (including the patient without pleocytosis) and/or blood. HPeV may cause severe disease in the neonatal period and patients presenting with such signs should be evaluated for HPeV. It also should be considered in sudden infant death syndrome. PMID:23742920

  17. Adolescent irritability: phenotypic associations and genetic links with depressed mood

    PubMed Central

    Stringaris, Argyris; Zavos, Helena; Leibenluft, Ellen; Maughan, Barbara; Eley, Thalia

    2013-01-01

    Objective Irritability has been proposed to underlie the developmental link between oppositional problems and depression. However, little is known about the genetic and environmental influences on irritability and its overlap with depression. This paper tests the hypothesis that the association between irritability and depression is accounted for by genetic factors. As such, it draws on the notion of “generalist genes” i.e., genes of general effect that underlie phenotypic overlap between disorders. Method The G1219 study, a UK-based twin sample (N=2651), was used in a cross-sectional and longitudinal design. Irritable and headstrong/hurtful dimensions of oppositional behavior were derived using factor analysis. Regression was used to estimate the association between depression and delinquency. Multivariate genetic analyses were used to estimate the genetic overlap between irritability versus headstrong/hurtful behaviors with depression and delinquency respectively. Results Irritability showed a significantly stronger phenotypic relationship with depression than delinquency, whereas headstrong/hurtful behaviors were more strongly related to delinquency than depression. In multivariate genetic analyses, the genetic correlation between irritability and depression (0.70; CI: 0.59-0.82) was significantly higher than that between irritability and delinquency (0.57; CI: 0.45-0.69); conversely, the genetic correlation between headstrong/hurtful behaviors and delinquency (0.80; CI: 0.72-0.86) was significantly higher than that between headstrong/hurtful behaviors and depression (0.46; CI: 0.36-0.57). In longitudinal models, the phenotypic association between irritability at Time 1 and depression at Time 2 was accounted for by the genetic association between irritability and depression at Time1. Conclusions The findings are consistent with the theory that genes with general effects underlie the relationship between irritability and depression. PMID:22193524

  18. BEHAVIORAL EVALUATION OF THE IRRITATING PROPERTIES OF OZONE

    EPA Science Inventory

    The sensory irritant properties of ozone have been considered to be responsible for symptoms that occur in humans after exposure. This assumption has not been studied explicitly. One way to assess the aversive properties of airborne irritants is to give the exposed individual an ...

  19. 16 CFR 1500.42 - Test for eye irritants.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Test for eye irritants. 1500.42 Section 1500.42 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS HAZARDOUS SUBSTANCES AND ARTICLES; ADMINISTRATION AND ENFORCEMENT REGULATIONS § 1500.42 Test for eye irritants. (a)(1) Six albino rabbits...

  20. Childhood Sexual Abuse and Psychosomatic Symptoms in Irritable Bowel Syndrome

    ERIC Educational Resources Information Center

    Ross, Colin A.

    2005-01-01

    Irritable bowel syndrome is characterized by chronic gastrointestinal symptoms without a demonstrable physical cause. In a subgroup of patients, irritable bowel syndrome may be part of a cluster of psychosomatic symptoms related to childhood sexual abuse. To investigate this possibility, the Dissociative Disorders Interview Schedule (DDIS), the…

  1. Lurasidone for the Treatment of Irritability Associated with Autistic Disorder

    ERIC Educational Resources Information Center

    Loebel, Antony; Brams, Matthew; Goldman, Robert S.; Silva, Robert; Hernandez, David; Deng, Ling; Mankoski, Raymond; Findling, Robert L.

    2016-01-01

    The aim of this study was to evaluate the short-term efficacy and safety of lurasidone in treating irritability associated with autistic disorder. In this multicenter trial, outpatients age 6-17 years who met DSM-IV-TR criteria for autistic disorder, and who demonstrated irritability, agitation, and/or self-injurious behaviors were randomized to…

  2. Rifaximin therapy of irritable bowel syndrome.

    PubMed

    Koo, Hoonmo L; Sabounchi, Saman; Huang, David B; DuPont, Herbert L

    2012-01-01

    Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain and altered bowel habits in the absence of specific organic pathology. Although the underlying pathogenesis of IBS is not well-understood, small intestinal bacterial overgrowth (SIBO) or other abnormalities in the gut flora is believed to contribute to the development of a subset of IBS cases. Rifaximin is a poorly absorbed antimicrobial with activity against enteric pathogens. A number of studies have shown a significant improvement in IBS symptoms with antibiotic therapy including rifaximin. In this review, we discuss the pharmacokinetics, in vitro susceptibility profile, and efficacy and safety data from clinical trials of rifaximin treatment of IBS. PMID:24833932

  3. Rifaximin Therapy of Irritable Bowel Syndrome

    PubMed Central

    Koo, Hoonmo L.; Sabounchi, Saman; Huang, David B.; DuPont, Herbert L.

    2012-01-01

    Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain and altered bowel habits in the absence of specific organic pathology. Although the underlying pathogenesis of IBS is not well-understood, small intestinal bacterial overgrowth (SIBO) or other abnormalities in the gut flora is believed to contribute to the development of a subset of IBS cases. Rifaximin is a poorly absorbed antimicrobial with activity against enteric pathogens. A number of studies have shown a significant improvement in IBS symptoms with antibiotic therapy including rifaximin. In this review, we discuss the pharmacokinetics, in vitro susceptibility profile, and efficacy and safety data from clinical trials of rifaximin treatment of IBS. PMID:24833932

  4. Irritable Bowel Syndrome: Yoga as Remedial Therapy

    PubMed Central

    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

  5. [Importance of diet in irritable bowel syndrome].

    PubMed

    Mearin, Fermín; Peña, Enrique; Balboa, Agustín

    2014-05-01

    About two-thirds of irritable bowel syndrome (IBS) patients associate their symptoms with certain foods. We reviewed food-related factors putatively associated with manifestations of IBS. Soluble fiber may improve constipation but frequently increases bloating and abdominal pain. Carbohydrate malabsorption seems to be more frequent in IBS. A low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet significantly reduces IBS symptoms and has been suggested as a therapeutic option. Serological screening for celiac disease should be done in patients without constipation. Moreover, non-celiac disease gluten sensitivity, defined as gluten intolerance once celiac disease and wheat allergy have been ruled out, should be considered in these patients. There is no specific diet for IBS patients but small and frequent meals, avoiding greasy foods, dairy products, many carbohydrates, caffeine and alcohol, is recommended. PMID:24582764

  6. Food components and irritable bowel syndrome.

    PubMed

    Gibson, Peter R; Varney, Jane; Malakar, Sreepurna; Muir, Jane G

    2015-05-01

    Ingestion of food has long been linked with gut symptoms, and there is increasing interest in using diet in the management of patients with irritable bowel syndrome (IBS). The West has developed an intense interest in specialized, restrictive diets, such as those that target multiple food groups, avoid gluten, or reduce fermentable oligo-, di-, and mono-saccharides and polyols. However, most gastroenterologists are not well educated about diets or their effects on the gut. It is important to understand the various dietary approaches, their putative mechanisms, the evidence that supports their use, and the benefits or harm they might produce. The concepts behind, and delivery of, specialized diets differ from those of pharmacologic agents. High-quality research is needed to determine the efficacy of different dietary approaches and the place of specific strategies. PMID:25680668

  7. Irritable Bowel Syndrome: Yoga as Remedial Therapy.

    PubMed

    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

  8. Allergen and irritant control: importance and implementation.

    PubMed

    Nelson, H S

    1998-01-01

    The Expert Panel Report 2. Guidelines for the Diagnosis and Management of Asthma (1) begins its section on controlling factors that precipitate or worsen asthma with the statement: "For successful long-term asthma management, it is essential to identify and reduce exposures to relevant allergens and irritants and to control other factors that have been shown to increase asthma symptoms and/or precipitate asthma exacerbations." The presence of allergy to indoor allergens and certain seasonal fungal spores has been found to be a risk factor for asthma in epidemiologic studies around the world. Generally between 70% and 85% of asthmatic populations studied have been reported to have positive skin-prick tests. Exposure of allergic patients to inhalant allergens increases airway inflammation, airway hyper-responsiveness, asthma symptoms, need for medication, severe attacks, and even death due to asthma. Environmental tobacco smoke exposure has been shown to increase the prevalence of childhood asthma and to increase asthma symptoms and bronchial hyperresponsiveness while reducing pulmonary function in children chronically exposed. Exposure to other indoor irritants, largely products of unvented combustion, has also been found to increase asthma symptoms. Outdoor air pollution increases asthma symptoms; levels of specific pollutants correlate with emergency room visits and hospitalization for asthma. Rhinitis/sinusitis and gastroesophageal reflux are commonly associated with asthma, and treatment of these conditions has been shown to improve asthma. In patients sensitive to aspirin and nonsteroidal anti-inflammatory drugs or metabisulfites, exposure to these agents can precipitate severe attacks of asthma. Viral infections are common causes for exacerbations of asthma. Infections with Mycoplasma pneumoniae and Chlamydia pneumoniae contribute to acute exacerbations and perhaps to long-term morbidity, as well. This chapter will discuss preventive and therapeutic measures

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

    PubMed

    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. PMID:18669179

  10. Is irritable bowel syndrome an organic disorder?

    PubMed Central

    El-Salhy, Magdy; Gundersen, Doris; Gilja, Odd Helge; Hatlebakk, Jan Gunnar; Hausken, Trygve

    2014-01-01

    Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is generally considered to be functional because there appears to be no associated anatomical defect. Stress and psychological factors are thought to play an important role in IBS. The gut neuroendocrine system (NES), which regulates all functions of the gastrointestinal tract, consists of endocrine cells that are scattered among the epithelial cells of the mucosa, and the enteric nervous system. Although it is capable of operating independently from the central nervous system (CNS), the gut NES is connected to and modulated by the CNS. This review presents evidence for the presence of an anatomical defect in IBS patients, namely in the gastrointestinal endocrine cells. These cells have specialized microvilli that project into the lumen and function as sensors for the luminal content and respond to luminal stimuli by releasing hormones into the lamina propria, which starts a chain reaction that progresses throughout the entire NES. The changes in the gastrointestinal endocrine cells observed in IBS patients are highly consistent with the other abnormalities reported in IBS patients, such as visceral hypersensitivity, dysmotility, and abnormal secretion. PMID:24574708

  11. Diet and the irritable bowel syndrome.

    PubMed

    Friedman, G

    1991-06-01

    Food intake plays a key role in triggering or perpetuating symptoms in patients with IBS. Evaluation of the impact of diet in the individual patient requires a precise dietary history and a 7-day prospective dietary analysis, which should include the quality and quantity of food consumed, chronologic sequence and nature of symptoms, and the frequency and consistency of bowel movements. The caloric density of the meal, total fat intake, the quantity and quality of lactose-containing foods, sorbitol, fructose, and the nature and quantity of soluble and insoluble fiber intake must be noted. Patients with reflux esophageal symptoms should eliminate foods that decrease LES pressure, such as chocolate, peppermint, alcohol, and coffee. Direct esophageal mucosal irritants such as tomatoes, citrus juices, sharp condiments, and alcohol should be limited. Gastric emptying is slowed with the ingestion of fats and soluble fiber. Small bowel motility is slowed by soluble fiber and fatty foods. Gaseous syndromes may be reduced by avoidance of smoking, chewing gum, excessive liquid intake, and carbonated drinks. The reduced intake of large amounts of lactose-containing foods, sorbitol, and fructose may limit postprandial bloating. Flatus production can be lowered by reducing fermentable carbohydrates such as beans, cabbage, lentils, brussel sprouts, and legumes. Soluble and insoluble fiber ingestion will reduce sigmoidal intraluminal pressures and overcome spastic constipation when given in progressive graded doses. Effective dietary manipulations remain a key factor in reducing symptoms in IBS. PMID:2066155

  12. Irritable bowel syndrome: emerging paradigm in pathophysiology.

    PubMed

    Lee, Yoo Jin; Park, Kyung Sik

    2014-03-14

    Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders, characterized by abdominal pain, bloating, and changes in bowel habits. These symptoms cannot be explained by structural abnormalities and there is no specific laboratory test or biomarker for IBS. Therefore, IBS is classified as a functional disorder with diagnosis dependent on the history taking about manifested symptoms and careful physical examination. Although a great deal of research has been carried out in this area, the pathophysiology of IBS is complex and not completely understood. Multiple factors are thought to contribute to the symptoms in IBS patients; altered gastrointestinal motility, visceral hypersensitivity, and the brain-gut interaction are important classical concepts in IBS pathophysiology. New areas of research in this arena include inflammation, postinfectious low-grade inflammation, genetic and immunologic factors, an altered microbiota, dietary factors, and enteroendocrine cells. These emerging studies have not shown consistent results, provoking controversy in the IBS field. However, certain lines of evidence suggest that these mechanisms are important at least a subset of IBS patients, confirming that IBS symptoms cannot be explained by a single etiological mechanism. Therefore, it is important to keep in mind that IBS requires a more holistic approach to determining effective treatment and understanding the underlying mechanisms. PMID:24627583

  13. Common gastrointestinal symptoms: irritable bowel syndrome.

    PubMed

    Fashner, Julia; Gitu, Alfred Chege

    2013-10-01

    The diagnosis of irritable bowel syndrome (IBS) should be considered when patients have had abdominal pain/discomfort, bloating, and change in bowel habits for 6 months. Patients may experience variation between periods of constipation and diarrhea. When evaluating patients with IBS, physicians should be alert for red flag symptoms, such as rectal bleeding, anemia, nighttime pain, and weight loss. Physicians also should consider other medical conditions that manifest similarly to IBS. Clinicians who are confident in diagnosing IBS based on symptoms typically do not obtain many tests unless the patient has red flag symptoms. Various etiologic mechanisms have been proposed for IBS, including abnormal bowel motility, inflammation, altered mucosal permeability, genetic predisposition, and visceral hypersensitivity. Lack of certainty about the etiology makes it difficult to develop effective management approaches; thus, management is directed toward symptom relief. Dietary changes, such as avoiding fermentable carbohydrates, may benefit some patients, especially those with bloating. Constipation-dominant IBS can be managed with antispasmodics, lubiprostone, or linaclotide, whereas diarrhea-dominant IBS can be managed with loperamide or alosetron, though the latter drug can cause ischemic colitis. For long-term therapy, tricyclic antidepressants or selective serotonin reuptake inhibitors have good efficacy. Peppermint oil and probiotics also may provide benefit. PMID:24124703

  14. Is irritable bowel syndrome an infectious disease?

    PubMed

    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. PMID:26819502

  15. Is irritable bowel syndrome an infectious disease?

    PubMed Central

    Thompson, John Richard

    2016-01-01

    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. PMID:26819502

  16. Irritable bowel syndrome and food interaction

    PubMed Central

    Cuomo, Rosario; Andreozzi, Paolo; Zito, Francesco Paolo; Passananti, Valentina; De Carlo, Giovanni; Sarnelli, Giovanni

    2014-01-01

    Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders in Western countries. Despite the high prevalence of this disorders, the therapeutic management of these patients is often unsatisfactory. A number of factors have been suggested to be involved in the pathogenesis of IBS, including impaired motility and sensitivity, increased permeability, changes in the gut microbiome and alterations in the brain-gut axis. Also food seems to play a critical role: the most of IBS patients report the onset or the exacerbation of their symptoms after the meals. Recently, an increasing attention has been paid to the role of food in IBS. In this review we summarize the most recent evidences about the role of diet on IBS symptoms. A diet restricted in fermentable, poorly absorbed carbohydrates and sugar alcohols has beneficial effects on IBS symptoms. More studies are needed to improve our knowledge about the relationship between food and IBS. However, in the foreseeable future, dietary strategies will represent one of the key tools in the therapeutic management of patients with IBS. PMID:25083057

  17. Molecular basis of the irritable bowel syndrome

    PubMed Central

    Vaiopoulou, Anna; Karamanolis, Georgios; Psaltopoulou, Theodora; Karatzias, George; Gazouli, Maria

    2014-01-01

    Irritable bowel syndrome (IBS) is a functional disorder characterized by abdominal pain, discomfort and bloating. The pathophysiology of IBS is poorly understood, but the presence of psychosocial basis is now known. There is an increasing number of publications supporting the role of genetics in IBS. Most of the variations are found in genes associated with the brain-gut axis, revealing the strong correlation of brain-gut axis and IBS. miRNAs, which play critical roles in physiological processes, are not well studied in IBS. However, so far there is found an involvement of alterations in miRNA expression or sequence, in IBS symptoms. IBS phenotype is affected by epigenetic alteration and environment. Changes in DNA and histone methylation are observed in patients who suffered childhood trauma or abuse, resulting in altered gene expression, such as the glucocorticoid receptor gene. Finally, diet is another factor associated with IBS, which may contribute to symptom onset. Certain foods may affect on bacterial metabolism and epigenetic modifications, predisposing to IBS. PMID:24574707

  18. [Irritable bowel syndrome, celiac disease and gluten].

    PubMed

    Mearin, Fermín; Montoro, Miguel

    2014-08-01

    For many years irritable bowel syndrome (IBS) and celiac disease (CD) have been considered 2 completely separate entities, with CD being clearly related to a permanent gluten intolerance and IBS having no relation with gluten ingestion. However IBS and CD symptoms may be indistinguishable, especially when diarrhea, bloating or abdominal pain predominate. In the last decade several studies have shown that the separation between CD and IBS is not so clear. Thus, some patients who have been diagnosed of IBS suffer in fact from CD. In addition, it seems that there is a group of patients who, without having CD, suffer gluten intolerance that cause them digestive symptoms similar to those of IBS. Gluten sensitivity is defined as the spectrum of morphological, immunological and functional abnormalities that respond to a gluten-free diet. This concept includes histological, immunological and clinical manifestations in the absence of evident morphological abnormalities. Therefore, it is mandatory to establish in a scientific way in which patients a gluten-free diet will be beneficial as well as when this is not justified. PMID:24029448

  19. The Intestinal Microbiota and Irritable Bowel Syndrome.

    PubMed

    Ringel, Yehuda; Ringel-Kulka, Tamar

    2015-01-01

    Irritable bowel syndrome (IBS) is the most prevalent and the best studied functional gastrointestinal disorder. The etiology and the pathogenesis of IBS are still not clear; however, recent studies have implicated a role for alterations in the intestinal microbiota (dysbiosis) in the pathophysiology of the disorder. Epidemiological observations have demonstrated that the development of IBS symptoms is often preceded by a disruption of the individual's normal intestinal microbiota, and microbiological studies have demonstrated compositional differences in the intestinal microbiota between patients with IBS patients and healthy controls. In addition, animal studies and a few recent human clinical studies have demonstrated that compositional changes in the intestinal microbiota in IBS are associated with relevant abnormal gastrointestinal and brain-gut axis functions that are often observed in patients with IBS. This article discusses points of interest from the current research on the microbiota-gut-brain interactions in IBS and highlights the relevance of the emerging data to our understanding of the disorder and the clinical implications for patients' care. PMID:26447966

  20. Irritable bowel syndrome: diagnosis and pathogenesis.

    PubMed

    El-Salhy, Magdy

    2012-10-01

    Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder that considerably reduces the quality of life. It further represents an economic burden on society due to the high consumption of healthcare resources and the non-productivity of IBS patients. The diagnosis of IBS is based on symptom assessment and the Rome III criteria. A combination of the Rome III criteria, a physical examination, blood tests, gastroscopy and colonoscopy with biopsies is believed to be necessary for diagnosis. Duodenal chromogranin A cell density is a promising biomarker for the diagnosis of IBS. The pathogenesis of IBS seems to be multifactorial, with the following factors playing a central role in the pathogenesis of IBS: heritability and genetics, dietary/intestinal microbiota, low-grade inflammation, and disturbances in the neuroendocrine system (NES) of the gut. One hypothesis proposes that the cause of IBS is an altered NES, which would cause abnormal GI motility, secretions and sensation. All of these abnormalities are characteristic of IBS. Alterations in the NES could be the result of one or more of the following: genetic factors, dietary intake, intestinal flora, or low-grade inflammation. Post-infectious IBS (PI-IBS) and inflammatory bowel disease-associated IBS (IBD-IBS) represent a considerable subset of IBS cases. Patients with PI- and IBD-IBS exhibit low-grade mucosal inflammation, as well as abnormalities in the NES of the gut. PMID:23066308

  1. Irritable Bowel Syndrome, Gut Microbiota and Probiotics

    PubMed Central

    Lee, Beom Jae

    2011-01-01

    Irritable bowel syndrome (IBS) is a complex disorder characterized by abdominal symptoms including chronic abdominal pain or discomfort and altered bowel habits. The etiology of IBS is multifactorial, as abnormal gut motility, visceral hypersensitivity, disturbed neural function of the brain-gut axis and an abnormal autonomic nervous system are all implicated in disease progression. Based on recent experimental and clinical studies, it has been suggested that additional etiological factors including low-grade inflammation, altered gut microbiota and alteration in the gut immune system play important roles in the pathogenesis of IBS. Therefore, therapeutic restoration of altered intestinal microbiota may be an ideal treatment for IBS. Probiotics are live organisms that are believed to cause no harm and result in health benefits for the host. Clinical efficacy of probiotics has been shown in the treatment or prevention of some gastrointestinal inflammation-associated disorders including traveler's diarrhea, antibiotics-associated diarrhea, pouchitis of the restorative ileal pouch and necrotizing enterocolitis. The molecular mechanisms, as cause of IBS pathogenesis, affected by altered gut microbiota and gut inflammation-immunity are reviewed. The effect of probiotics on the gut inflammation-immune systems and the results from clinical trials of probiotics for the treatment of IBS are also summarized. PMID:21860817

  2. Irritable bowel syndrome and food interaction.

    PubMed

    Cuomo, Rosario; Andreozzi, Paolo; Zito, Francesco Paolo; Passananti, Valentina; De Carlo, Giovanni; Sarnelli, Giovanni

    2014-07-21

    Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders in Western countries. Despite the high prevalence of this disorders, the therapeutic management of these patients is often unsatisfactory. A number of factors have been suggested to be involved in the pathogenesis of IBS, including impaired motility and sensitivity, increased permeability, changes in the gut microbiome and alterations in the brain-gut axis. Also food seems to play a critical role: the most of IBS patients report the onset or the exacerbation of their symptoms after the meals. Recently, an increasing attention has been paid to the role of food in IBS. In this review we summarize the most recent evidences about the role of diet on IBS symptoms. A diet restricted in fermentable, poorly absorbed carbohydrates and sugar alcohols has beneficial effects on IBS symptoms. More studies are needed to improve our knowledge about the relationship between food and IBS. However, in the foreseeable future, dietary strategies will represent one of the key tools in the therapeutic management of patients with IBS. PMID:25083057

  3. The Treatment of Irritable Bowel Syndrome

    PubMed Central

    Weiser, Kirsten; De Lee, Ryan

    2009-01-01

    Irritable bowel syndrome (IBS) is a highly prevalent functional bowel disorder routinely encountered by healthcare providers. Although not life-threatening, this chronic disorder reduces patients’ quality of life and imposes a significant economic burden to the healthcare system. IBS is no longer considered a diagnosis of exclusion that can only be made after performing a battery of expensive diagnostic tests. Rather, IBS should be confidently diagnosed in the clinic at the time of the first visit using the Rome III criteria and a careful history and physical examination. Treatment options for IBS have increased in number in the past decade and clinicians should not be limited to using only fiber supplements and smooth muscle relaxants. Although all patients with IBS have symptoms of abdominal pain and disordered defecation, treatment needs to be individualized and should focus on the predominant symptom. This paper will review therapeutic options for the treatment of IBS using a tailored approach based on the predominant symptom. Abdominal pain, bloating, constipation and diarrhea are the four main symptoms that can be addressed using a combination of dietary interventions and medications. Treatment options include probiotics, antibiotics, tricyclic antidepressants, selective serotonin reuptake inhibitors and agents that modulate chloride channels and serotonin. Each class of agent will be reviewed using the latest data from the literature. PMID:21180545

  4. Irritable bowel syndrome: Diagnosis and pathogenesis

    PubMed Central

    El-Salhy, Magdy

    2012-01-01

    Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder that considerably reduces the quality of life. It further represents an economic burden on society due to the high consumption of healthcare resources and the non-productivity of IBS patients. The diagnosis of IBS is based on symptom assessment and the Rome III criteria. A combination of the Rome III criteria, a physical examination, blood tests, gastroscopy and colonoscopy with biopsies is believed to be necessary for diagnosis. Duodenal chromogranin A cell density is a promising biomarker for the diagnosis of IBS. The pathogenesis of IBS seems to be multifactorial, with the following factors playing a central role in the pathogenesis of IBS: heritability and genetics, dietary/intestinal microbiota, low-grade inflammation, and disturbances in the neuroendocrine system (NES) of the gut. One hypothesis proposes that the cause of IBS is an altered NES, which would cause abnormal GI motility, secretions and sensation. All of these abnormalities are characteristic of IBS. Alterations in the NES could be the result of one or more of the following: genetic factors, dietary intake, intestinal flora, or low-grade inflammation. Post-infectious IBS (PI-IBS) and inflammatory bowel disease-associated IBS (IBD-IBS) represent a considerable subset of IBS cases. Patients with PI- and IBD-IBS exhibit low-grade mucosal inflammation, as well as abnormalities in the NES of the gut. PMID:23066308

  5. Odor and irritation effects of a volatile organic compound mixture

    SciTech Connect

    Hudnell, H.K.; Otto, O.D.; Mohave, L.; House, D.E.

    1990-01-01

    Human exposure to volatile organic compounds elicits a variety of symptoms, many of which are thought to be mediated by the olfactory and trigeminal systems. The report describes evidence indicating that perceived odor intensity diminishes during prolonged exposure, whereas irritation of the eyes and throat reaches an asymptotic level. Both odor and irritation appear to influence the assessment of air quality. Results of the study will be used in designing future indoor air studies related to sick building syndrome.

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

    PubMed

    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. PMID:25194867

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

    PubMed

    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. PMID:20557579

  8. Patterns of alternation in irritable bowel syndrome

    PubMed Central

    CHIRA, ALEXANDRA; FILIP, MIHAELA; DUMITRAŞCU, DAN LUCIAN

    2016-01-01

    Background and aims Irritable bowel syndrome (IBS) is one of the most frequent functional gastrointestinal disorders, having its subtypes related to the predominant bowel pattern: IBS with diarrhea (IBS-D), IBS with constipation (IBS-C), mixed IBS (IBS-M) or alternating IBS (IBS-A). Some patients alternate between subtypes (IBS-A). We looked for the prevalence of alternation between subtypes in patients with IBS. We also analyzed changes in pharmacological therapy specifically addressed to IBS. Methods We performed a retrospective observational study that included 60 patients diagnosed with IBS according to Rome III criteria. Patients were asked using a detailed structured interview about their stool form changes regarding previous six months. Alternators were defined as patients that changed IBS subtype over time (previous six months). Results Out of the 60 patients diagnosed with IBS, 18 patients (30%) were alternators. Of these, 8 patients (44%) changed twice the subtype. Two patients (66.66%) of the IBS-M subgroup shifted between subtypes. Eight patients (44.44%) changed medication over the six months. Four patients (22.2%) of the alternators were on double association of therapy (antispasmodics) addressed to IBS. Four patients (22.22%) discontinued medication. Conclusions Patients with IBS often change between subtypes even within six months. Alternators in our pilot study represented 30% of IBS patients. IBS-M seems to be the least stable phenotype. The rarest change is the shift between IBS-C and IBS-D. Alternators also often change their pharmacological treatment (antispasmodics). PMID:27152072

  9. [Irritable Bowel Syndrome treatment: a multidisciplinary approach].

    PubMed

    Shani-Zur, Dana; Wolkomir, Keren

    2015-01-01

    Irritable Bowel Syndrome affects 9-23% of the general population. This diagnosis contributes to more frequent doctor visits and multiple consultations by patients. The current approach to treating IBS is symptomatic and consists of a regimen of first line pharmacological treatment options; the use of anti-depressant drugs is also common. The efficiency of complementary medicine in the treatment of IBS has been studied in the last few years. Qualitative multidisciplinary approach studies, using personalized medicines with complementary therapies are needed. We present the case of a 39-year-old woman with a diagnosis of IBS since 2009, who complained about gastrointestinal symptoms since the age of 13 and severe episodes of spasmodic stomach aches in the last year self-ranked as 10, on a 0-10 scale; 3-4 episodes a month, which last for 5 days, accompanied by severe flatulence and bloating. In addition, she has constipation (one bowel movement every 10 days), alternating with multiple diarrheic bowel movements (6 times a day). Using a multidisciplinary approach, including medicinal care, Chinese medicine, reflexology and naturopathy resulted in significant improvement in symptoms and quality of life, as well as gradual reduction of drugs, approved by her physician. Stomach ache self-ranked now as 1, on a 0-10 scale; and flatulence and bloating self-ranked as mild. Bowel movement frequency increased and is now every other day. She no longer has diarrheic and/or multiple bowel movements. This case report emphasizes the importance of integrative treatment in IBS and its benefit in improving patients' quality of life. PMID:25796677

  10. Irritable Bowel Syndrome: A Clinical Review.

    PubMed

    Cashman, Michael D; Martin, Daniel K; Dhillon, Sonu; Puli, Srinivas R

    2016-01-01

    Symptoms of irritable bowel syndrome (IBS) are common in population studies including chronic abdominal pain associated with altered bowel habits. Patients often have associated gastrointestinal and somatic symptoms suggesting a possible common contributing mechanism, but the heterogeneous symptom patterns of individual patients make generalizations difficult. The pathophysiology of IBS is incompletely understood but includes disturbances of the brain-gut axis. Central mechanisms are: the psychosocial history and environment, dysfunctional brain processing of peripheral signals attributed to the intestine including the enteric nervous system, the microbiome and the innate and adaptive immune system. As a result there is visceral hypersensitivity and disturbed intestinal secretory and motor activity. Some mechanisms of visceral pain hypersensitivity may overlap with other pain syndromes including fibromyalgia (FMS). Central Sensitization (CS) would offer a way to conceptualize an integration of life experience and psychologic response into a biopsychosocial framework of pathophysiology, diagnosis and treatment of IBS. Corticotropin-releasing factor, a principle regulator in the stress and pain response may contribute to a neuroendocrine mechanism for the brain-gut interaction. The positive diagnostic approach to IBS symptoms to avoid excess testing and enhance the patient-provider therapeutic relationship requires the recognition of the "cluster" of IBS symptoms while identifying "alarm" symptoms requiring specific attention. The severity of the symptoms and other individual psychosocial factors characterize patients who seek medical care. The presence of significant psychosocial comorbidities adds to the complexity of management which often requires a multidisciplinary approach. Several treatment options exist but no single method is effective for all the symptoms of IBS. The therapeutic benefit of the well-executed physician-patient relationship is considered

  11. Breath tests and irritable bowel syndrome.

    PubMed

    Rana, Satya Vati; Malik, Aastha

    2014-06-28

    Breath tests are non-invasive tests and can detect H₂ and CH₄ gases which are produced by bacterial fermentation of unabsorbed intestinal carbohydrate and are excreted in the breath. These tests are used in the diagnosis of carbohydrate malabsorption, small intestinal bacterial overgrowth, and for measuring the orocecal transit time. Malabsorption of carbohydrates is a key trigger of irritable bowel syndrome (IBS)-type symptoms such as diarrhea and/or constipation, bloating, excess flatulence, headaches and lack of energy. Abdominal bloating is a common nonspecific symptom which can negatively impact quality of life. It may reflect dietary imbalance, such as excess fiber intake, or may be a manifestation of IBS. However, bloating may also represent small intestinal bacterial overgrowth. Patients with persistent symptoms of abdominal bloating and distension despite dietary interventions should be referred for H₂ breath testing to determine the presence or absence of bacterial overgrowth. If bacterial overgrowth is identified, patients are typically treated with antibiotics. Evaluation of IBS generally includes testing of other disorders that cause similar symptoms. Carbohydrate malabsorption (lactose, fructose, sorbitol) can cause abdominal fullness, bloating, nausea, abdominal pain, flatulence, and diarrhea, which are similar to the symptoms of IBS. However, it is unclear if these digestive disorders contribute to or cause the symptoms of IBS. Research studies show that a proper diagnosis and effective dietary intervention significantly reduces the severity and frequency of gastrointestinal symptoms in IBS. Thus, diagnosis of malabsorption of these carbohydrates in IBS using a breath test is very important to guide the clinician in the proper treatment of IBS patients. PMID:24976698

  12. Irritable bowel syndrome: A clinical review

    PubMed Central

    Soares, Rosa LS

    2014-01-01

    Irritable bowel syndrome (IBS) remains a clinical challenge in the 21st century. It’s the most commonly diagnosed gastrointestinal condition and also the most common reason for referral to gastroenterology clinics. Its can affect up to one in five people at some point in their lives, and has a significantly impact of life quality and health care utilization. The prevalence varies according to country and criteria used to define IBS. Various mechanisms and theories have been proposed about its etiology, but the biopsychosocial model is the most currently accepted for IBS. The complex of symptoms would be the result of the interaction between psychological, behavioral, psychosocial and environmental factors. The diagnosis of IBS is not confirmed by a specific test or structural abnormality. It is made using criteria based on clinical symptoms such as Rome criteria, unless the symptoms are thought to be atypical. Today the Rome Criteria III is the current gold-standard for the diagnoses of IBS. Secure positive evidence of IBS by means of specific disease marker is currently not possible and cannot be currently recommended for routine diagnosis. There is still no clinical evidence to recommend the use of biomarkers in blood to diagnose IBS. However, a number of different changes in IBS patients were demonstrated in recent years, some of which can be used in the future as a diagnostic support. IBS has no definitive treatment but could be controlled by non-pharmacologic management eliminating of some exacerbating factors such certain drugs, stressor conditions and changes in dietary habits.The traditional pharmacologic management of IBS has been symptom based and several drugs have been used. However, the cornerstone of its therapy is a solid patient physician relationship. This review will provide a summary of pathophysiology, diagnostic criteria and current and emerging therapies for IBS. PMID:25232249

  13. Breath tests and irritable bowel syndrome

    PubMed Central

    Rana, Satya Vati; Malik, Aastha

    2014-01-01

    Breath tests are non-invasive tests and can detect H2 and CH4 gases which are produced by bacterial fermentation of unabsorbed intestinal carbohydrate and are excreted in the breath. These tests are used in the diagnosis of carbohydrate malabsorption, small intestinal bacterial overgrowth, and for measuring the orocecal transit time. Malabsorption of carbohydrates is a key trigger of irritable bowel syndrome (IBS)-type symptoms such as diarrhea and/or constipation, bloating, excess flatulence, headaches and lack of energy. Abdominal bloating is a common nonspecific symptom which can negatively impact quality of life. It may reflect dietary imbalance, such as excess fiber intake, or may be a manifestation of IBS. However, bloating may also represent small intestinal bacterial overgrowth. Patients with persistent symptoms of abdominal bloating and distension despite dietary interventions should be referred for H2 breath testing to determine the presence or absence of bacterial overgrowth. If bacterial overgrowth is identified, patients are typically treated with antibiotics. Evaluation of IBS generally includes testing of other disorders that cause similar symptoms. Carbohydrate malabsorption (lactose, fructose, sorbitol) can cause abdominal fullness, bloating, nausea, abdominal pain, flatulence, and diarrhea, which are similar to the symptoms of IBS. However, it is unclear if these digestive disorders contribute to or cause the symptoms of IBS. Research studies show that a proper diagnosis and effective dietary intervention significantly reduces the severity and frequency of gastrointestinal symptoms in IBS. Thus, diagnosis of malabsorption of these carbohydrates in IBS using a breath test is very important to guide the clinician in the proper treatment of IBS patients. PMID:24976698

  14. Eye irritation of low-irritant cosmetic formulations: correlation of in vitro results with clinical data and product composition.

    PubMed

    Debbasch, Caroline; Ebenhahn, Catherine; Dami, Nadia; Pericoi, Marc; Van den Berghe, Christine; Cottin, Martine; Nohynek, Gerhard J

    2005-01-01

    Alternative methods to the Draize eye irritation test, such as the hen's egg test-chorioallantoic membrane (HET-CAM) or the bovine corneal opacity and permeability (BCOP) tests, are currently used to evaluate the irritant potential of cosmetic or consumer products. Although, for strong irritants, the results of these tests correlate well with those of the Draize test, they appear to be less suited to identify mild irritants. In order to improve the sensitivity of alternative eye irritation tests, we developed a novel method that uses a human corneal epithelial cell line (CEPI), and the endpoints of cytotoxicity and IL-8 release. Twelve make-up removers were assessed by the HET-CAM, BCOP and CEPI tests, as well as in a clinical in-use test under ophthalmological control after their application to the external eye lid. In addition, we investigated the impact of osmolality and raw material composition on in vitro and clinical results and compared the in vitro results with those of clinical studies. Overall, although HET-CAM results were unrelated to eye discomfort and adverse clinical signs, they correlated mainly with the presence and concentration of surfactants in the test articles. BCOP scores were unrelated to clinical signs, but related mainly to glycol and sodium lactate content and concentration in the test articles. Cytotoxicity in CEPI mainly correlated with presence and concentrations of surfactants, and IL-8 release to clinical signs and/or glycol and sodium lactate concentrations. Overall, IL-8 release appeared to be the most sensitive and reliable endpoint to predict human eye tolerance to mildly irritant products. Although our results suggest that the IL-8 assay appears to be a promising screen for borderline-irritant formulations, further experiments are required to confirm and validate these preliminary results. PMID:15582208

  15. The Influence of Humidity on Assessing Irritation Threshold of Ammonia.

    PubMed

    Monsé, Christian; Sucker, Kirsten; Hoffmeyer, Frank; Jettkant, Birger; Berresheim, Hans; Bünger, Jürgen; Brüning, Thomas

    2016-01-01

    A large number of occupational exposure limit values (OELs) are based on avoiding of sensory irritation of the eyes and the upper respiratory tract. In order to investigate the chemosensory effect range of a chemical, odor and sensory irritation thresholds (lateralization thresholds, LTs) can be assessed. Humidity affects olfactory function and thus influences odor thresholds; however, a similar effect has not been shown for sensory irritation thresholds. The purpose of the present study was to explore whether LTs for ammonia vapor vary depending on the water vapor content of the inspired stimulus. Eight healthy nonsmoking volunteers were simultaneously exposed to ammonia vapor through one nostril and clean air through the other and were asked to determine which nostril received the chemical. Within experimental runs, ascending ammonia concentrations (60-350 ppm) that were either dry or humidified were administered at fixed time intervals. Geometric mean LTs obtained at wet (181 ppm) or dry (172 ppm) conditions did not differ significantly (P = 0.19) and were within the range of those reported by previous studies. These results suggest that humidity is not a critical factor in determining sensory irritation thresholds for ammonia, and future studies will examine if these findings are transferable to sensory irritation thresholds for other chemicals. PMID:27379250

  16. The Influence of Humidity on Assessing Irritation Threshold of Ammonia

    PubMed Central

    Sucker, Kirsten; Jettkant, Birger; Berresheim, Hans; Brüning, Thomas

    2016-01-01

    A large number of occupational exposure limit values (OELs) are based on avoiding of sensory irritation of the eyes and the upper respiratory tract. In order to investigate the chemosensory effect range of a chemical, odor and sensory irritation thresholds (lateralization thresholds, LTs) can be assessed. Humidity affects olfactory function and thus influences odor thresholds; however, a similar effect has not been shown for sensory irritation thresholds. The purpose of the present study was to explore whether LTs for ammonia vapor vary depending on the water vapor content of the inspired stimulus. Eight healthy nonsmoking volunteers were simultaneously exposed to ammonia vapor through one nostril and clean air through the other and were asked to determine which nostril received the chemical. Within experimental runs, ascending ammonia concentrations (60–350 ppm) that were either dry or humidified were administered at fixed time intervals. Geometric mean LTs obtained at wet (181 ppm) or dry (172 ppm) conditions did not differ significantly (P = 0.19) and were within the range of those reported by previous studies. These results suggest that humidity is not a critical factor in determining sensory irritation thresholds for ammonia, and future studies will examine if these findings are transferable to sensory irritation thresholds for other chemicals. PMID:27379250

  17. Meditation over medication for irritable bowel syndrome? On exercise and alternative treatments for irritable bowel syndrome.

    PubMed

    Asare, Fredrick; Störsrud, Stine; Simrén, Magnus

    2012-08-01

    Complimentary alternative treatment regimens are widely used in irritable bowel syndrome (IBS), but the evidence supporting their use varies. For psychological treatment options, such as cognitive behavioral therapy, mindfulness, gut-directed hypnotherapy, and psychodynamic therapy, the evidence supporting their use in IBS patients is strong, but the availability limits their use in clinical practice. Dietary interventions are commonly included in the management of IBS patients, but these are primarily based on studies assessing physiological function in relation to dietary components, and to a lesser degree upon research examining the role of dietary components in the therapeutic management of IBS. Several probiotic products improve a range of symptoms in IBS patients. Physical activity is of benefit for health in general and recent data implicates its usefulness also for IBS patients. Acupuncture does not seem to have an effect beyond placebo in IBS. A beneficial effect of some herbal treatments has been reported. PMID:22661301

  18. Estimation of proinflammatory biomarkers of skin irritation by dermal microdialysis following exposure with irritant chemicals.

    PubMed

    Fulzele, Suniket V; Babu, R J; Ahaghotu, E; Singh, Mandip

    2007-07-31

    The aim of the present study was to quantify the release of proinflammatory biomarkers by dermal microdialysis after topical exposure with irritant chemicals, Jet fuel (JP-8) and xylene in rat skin. Occlusive dermal exposure (2h) was carried out with 230microl of JP-8 or xylene using Hill top chambers((R)). Linear microdialysis probes (10mm) were inserted in the dermis under urethane anesthesia. The dialysis fluid was pumped at a flow rate of 2microl/min and the dialysate was collected for 7h following probe insertion. The expression of substance P (SP), calcitonin-gene related peptide (CGRP) and prostaglandin E(2) (PGE(2)) in the dialysate following microdialysis was measured by enzyme immunoassay (EIA). The effect of pretreatment with an SP antagonist (SR-140333) and a PGE(2) inhibitor (celecoxib), 6 and 18h before the application of JP-8 was also assessed to further establish the sensitivity of the microdialysis set up. On similar lines, untreated and capsaicin treated control experiments were performed to compare with the SP release following JP-8 treatment. Further, we also investigated the SP release following topical application of xylene. The mean concentrations of SP after the application of JP-8 (90.01+/-3.31) and 3h after its removal (58.66+/-9.36) indicated that JP-8 induced significantly higher release of SP as compared to the baseline value (P<0.05). The release of SP following JP-8 treatment (58.66+/-9.36pg/ml) was comparable to capsaicin (58.18+/-11.29pg/ml). JP-8 exposure resulted in a significant increase (P<0.001) in PGE(2) levels over the baseline control at the end of 1 and 2h of exposure. JP-8 treatment also produced significant increase (P<0.001) in PGE(2) levels as compared to the untreated control during occlusion and 1h following its removal. There was a significant drop (P<0.05) in the PGE(2) levels by the end of 3h following exposure. Pretreatment with SR-140333 and celecoxib significantly reduced (P<0.05) SP and PGE(2) release induced

  19. Alternative methods for the replacement of eye irritation testing.

    PubMed

    Lotz, Christian; Schmid, Freia F; Rossi, Angela; Kurdyn, Szymon; Kampik, Daniel; De Wever, Bart; Walles, Heike; Groeber, Florian K

    2016-01-01

    In the last decades significant regulatory attempts were made to replace, refine and reduce animal testing to assess the risk of consumer products for the human eye. As the original in vivo Draize eye test has been criticized for limited predictivity, costs and ethical issues, several animal-free test methods have been developed to categorize substances according to the global harmonized system (GHS) for eye irritation.This review summarizes the progress of alternative test methods for the assessment of eye irritation. Based on the corneal anatomy and the current knowledge of the mechanisms causing eye irritation, different ex vivo and in vitro methods will be presented and discussed in regard of possible limitations and their status of regulatory acceptance. In addition to established in vitro models, this review will also highlight emerging, full thickness cornea models that might be applicable to predict all GHS categories. PMID:26626125

  20. In vitro and human testing strategies for skin irritation.

    PubMed

    Robinson, M K; Osborne, R; Perkins, M A

    2000-01-01

    Prior to the manufacture, transport, and marketing of chemicals or products, it is critical to assess their potential for skin toxicity (corrosion or irritation), thereby protecting the worker and consumer from adverse skin effects due to intended or accidental skin exposure. Traditionally, animal testing procedures have provided the data needed to assess the more severe forms of skin toxicity, and current regulations may require animal test data before permission can be obtained to manufacture, transport, or market chemicals or the products that contain them. In recent years, the use of animals to assess skin safety has been opposed by some as inhumane and unnecessary. The conflicting needs of the industrial toxicologist to (1) protect human safety, (2) comply with regulations, and (3) reduce animal testing have led to major efforts to develop alternative, yet predictive, test methods. A variety of in vitro skin corrosion test methods have been developed and several have successfully passed initial international validation. These have included skin or epidermal equivalent assays that have been shown to distinguish corrosive from noncorrosive chemicals. These skin/epidermal equivalent assays have also been modified and used to assess skin irritation potential relative to existing human exposure test data. The data show a good correlation between in vitro assay data and different types of human skin irritation data for both chemicals and consumer products. The effort to eliminate animal tests has also led to the development of a novel human patch test for assessment of acute skin irritation potential. A case study shows the benefits of in vitro and human skin irritation tests compared to the animal tests they seek to replace, and strategies now exist to adequately assess human skin irritation potential without the need to rely on animal test methods. PMID:11083109

  1. [Current approaches to the diagnosis and treatment of irritable bowel syndrome].

    PubMed

    Kharchenko, N V; Chernenko, V V

    2001-01-01

    Modern definition, classifications, diagnosis and treatment of irritable bowel syndrome (IBS) are presented together with results of treatment of 30 patients with irritable bowel syndrome with the new selective calcium-channel blocker dicetel. PMID:11881362

  2. Perceived Informativeness of and Irritation with Local Advertising.

    ERIC Educational Resources Information Center

    Pasadeos, Yorgo

    1990-01-01

    Surveys mall shoppers to determine the relative informativeness of retail advertising. Finds that newspaper advertisements are considered the most informative with radio commercials next and television commercials least. Finds that newspaper ads are more irritating than radio or television advertising. Finds older and wealthier shoppers more…

  3. Acute inhalation toxicity and sensory irritation of dimethylamine. [Rats, mice

    SciTech Connect

    Steinhagen, W.H.; Swenberg, J.A.; Barrow, C.S.

    1982-06-01

    The sensory irritation potential of dimethylamine (DMA) inhalation on male Fischer-344 rats and male Swiss-Webster mice was evaluated by measuring the reflex decrease in respiratory rate. In addition, the six hour LC/sub 50/ for rats exposed to dimetylamine was established. Groups of 3 or 4 rats and mice were exposed for 10 minutes to concentrations of DMA ranging from 49 to 1576 ppm during which time the respiratory rate was monitored and recorded. Sensory irritation concentration-response curves were obtained and RD/sub 50/ values (concentration which elicits a 50% decrease in respiratory rate) were determined to be 573 and 511 ppm for rats and mice, respectively. In another set of experiments seven groups of male rats were exposed to concentrations of DMA ranging from 600 to 6119 ppm for six hours. Mortality counts were made during and for 48 hours post exposure. The six hour LC/sub 50/ was determined to be 4540 ppm. Histopathologic examination of the respiratory tract revealed concentration related changes ranging from ulceration and necrosis to rhinitis, tracheitis, and emphysema. Overall, DMA was found to be less potent as a sensory irritant than other airborne irritants.

  4. Sensitivity to environmental irritants and quality of life in COPD

    PubMed Central

    Ternesten-Hasséus, Ewa; Larsson, Sven; Millqvist, Eva

    2011-01-01

    It is a common clinical experience that patients with chronic obstructive pulmonary disease (COPD) complain of airway symptoms provoked by environmental irritants like chemicals and scents, although few studies can confirm such connections. The aim was to study the prevalence of airway symptoms induced by chemicals and scents in a group of patients with newly diagnosed CPOD and to analyze any relation to illness severity and quality of life. Eighty-one patients with COPD were recruited to the study. By mail they were asked to answer three questionnaires regarding symptoms, quality of life, and social and emotional influence of airway symptoms induced by environmental irritants. A majority (62%) of the COPD patients claimed to be hyperreactive to chemicals and scents. As a group they scored higher on a questionnaire measuring social and emotional influences of such environmental irritants compared to healthy control subjects. Further, high scores were more common among patients with a very severe form of COPD and among patients with regular use of β2-stimulants. High scores were also associated with significantly more airway symptoms and, in some aspects, with impaired quality of life. In conclusion, the results of this study show that airway symptoms induced by environmental irritants are common in patients with COPD and that this increased airway sensitivity follows the impairment of lung capacity. The mechanisms behind this remain unclear. PMID:22259245

  5. Sensitivity to environmental irritants and quality of life in COPD.

    PubMed

    Ternesten-Hasséus, Ewa; Larsson, Sven; Millqvist, Eva

    2011-01-01

    It is a common clinical experience that patients with chronic obstructive pulmonary disease (COPD) complain of airway symptoms provoked by environmental irritants like chemicals and scents, although few studies can confirm such connections. The aim was to study the prevalence of airway symptoms induced by chemicals and scents in a group of patients with newly diagnosed CPOD and to analyze any relation to illness severity and quality of life. Eighty-one patients with COPD were recruited to the study. By mail they were asked to answer three questionnaires regarding symptoms, quality of life, and social and emotional influence of airway symptoms induced by environmental irritants. A majority (62%) of the COPD patients claimed to be hyperreactive to chemicals and scents. As a group they scored higher on a questionnaire measuring social and emotional influences of such environmental irritants compared to healthy control subjects. Further, high scores were more common among patients with a very severe form of COPD and among patients with regular use of β(2)-stimulants. High scores were also associated with significantly more airway symptoms and, in some aspects, with impaired quality of life. In conclusion, the results of this study show that airway symptoms induced by environmental irritants are common in patients with COPD and that this increased airway sensitivity follows the impairment of lung capacity. The mechanisms behind this remain unclear. PMID:22259245

  6. 16 CFR 1500.42 - Test for eye irritants.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... CPSC's animal testing policy set forth in 16 CFR 1500.232. A weight-of-evidence analysis or a validated... interpreting ocular irritation test results, the CPSC animal testing policy Web page at http://www.cpsc.gov.... Washington, DC: U.S. Environmental Protection Agency. (Available:...

  7. [Introduce a new vitro replacement method of skin irritation test].

    PubMed

    Sun, Likui; Hou, Li; Shi, Yanping

    2011-09-01

    A series of new replacement methods of skin irritation test such as EpiSkin, EpiDermSIT (updated) and SkinEthicRHE have been validated by ECVAM. Due to it, animals are protected to the full extent. These provide more methods for biological evaluation of medical devices. PMID:22242390

  8. Underlying molecular and cellular mechanisms in childhood irritable bowel syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Irritable bowel syndrome (IBS) affects a large number of children throughout the world. The symptom expression of IBS is heterogeneous, and several factors which may be interrelated within the IBS biopsychosocial model play a role. These factors include visceral hyperalgesia, intestinal permeability...

  9. 16 CFR 1500.42 - Test for eye irritants.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... materials that might produce eye irritation. Both eyes of each animal in the test group shall be examined... injection of the blood vessels), or if such substance produces in the conjunctivae (excluding the cornea and... in the test group exhibit a positive reaction. If only one animal exhibits a positive reaction,...

  10. Subtypes of irritable bowel syndrome in children and adolescents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pharmacologic treatments for irritable bowel syndrome (IBS) and medical management of symptoms are increasingly based on IBS subtype, so it is important to accurately differentiate patients. Few studies have classified subtypes of pediatric IBS, and conclusions have been challenged by methodologic l...

  11. Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The intestinal microbiomes of healthy children and pediatric patients with irritable bowel syndrome (IBS) are not well defined. Studies in adults have indicated that the gastrointestinal microbiota could be involved in IBS. We analyzed 71 samples from 22 children with IBS (pediatric Rome III criteri...

  12. Conditioned pain modulation in women with irritable bowel syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Evidence suggests that patients with irritable bowel syndrome (IBS) are more vigilant to pain-associated stimuli. The aims of this study were to compare women with IBS (n = 20) to healthy control (HC, n = 20) women on pain sensitivity, conditioned pain modulation (CPM) efficiency, and salivary corti...

  13. Urinary proteome analysis of irritable bowel syndrome (IBS) symptom subgroups

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder characterized by chronic abdominal pain associated with alterations in bowel function. Given the heterogeneity of the symptoms, multiple pathophysiologic factors are suspected to play a role. We classified women with IBS i...

  14. The simulation of behaviors of photodetectors under pulsed laser irritation

    NASA Astrophysics Data System (ADS)

    Zheng, Xin; Cheng, Xiang-ai; Yu, Xiangyang; Qian, Le; Jiang, Tian

    2013-05-01

    Precise simulation of transient electrical behaviors of photodetectors under laser irradiation is becoming an increasingly concern. It not only can allow a detailed study and analysis of complex phenomena that cannot be carried out by experiments, but gives valuable information about the physical mechanisms which ultimately determine the response of the photodetectors. Finite difference numerical technique is adopted in the simulation to calculate the current response of photodetectors under pulsed laser irritation in this paper. To simulation the behaviors of photodetectors under pulsed laser irritation, the transport and trapping of carries and external circuit effects, including load resistance, junction capacitance, and parasitic capacitance, are considered. The basic equations governing the carrier behaviors are solved, including Poisson's equation, the carrier motion equations, and the carrier continuity equations. The simulated transient carrier density and velocities are present, as well as corresponding transient electric field distributions. The behaviors of electrons and holes and its contributions to the external current response are analyzed. Then a general and brief image of the transient progress of photodetectors under pulsed laser irritation is established. How the carrier is induced, transported, and trapped and whether they make any significant contribution to the external current response are discussed. Besides, bias dependent response is also studied. Higher bias will improver the behaviors of photodetectors under pulsed laser irritation. The simulated results and theory analysis will show valuable clue for future research on the behaviors of photodetectors irradiated by pulsed laser.

  15. Acupuncture for treatment of irritable bowel syndrome

    PubMed Central

    Manheimer, Eric; Cheng, Ke; Wieland, L. Susan; Min, Li Shih; Shen, Xueyong; Berman, Brian M; Lao, Lixing

    2013-01-01

    Background Irritable bowel syndrome (IBS) is a common, costly, and difficult to treat disorder that impairs health-related quality of life and work productivity. Evidence-based treatment guidelines have been unable to provide guidance on the effects of acupuncture for IBS because the only previous systematic review included only small, heterogeneous and methodologically unsound trials. Objectives The primary objectives were to assess the efficacy and safety of acupuncture for treating IBS. Search methods MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the Cumulative Index to Nursing and Allied Health, and the Chinese databases Sino-Med, CNKI, and VIP were searched through November 2011. Selection criteria Randomized controlled trials (RCTs) that compared acupuncture with sham acupuncture, other active treatments, or no (specific) treatment, and RCTs that evaluated acupuncture as an adjuvant to another treatment, in adults with IBS were included. Data collection and analysis Two authors independently assessed the risk of bias and extracted data. We extracted data for the outcomes overall IBS symptom severity and health-related quality of life. For dichotomous data (e.g. the IBS Adequate Relief Question), we calculated a pooled relative risk (RR) and 95% confidence interval (CI) for substantial improvement in symptom severity after treatment. For continuous data (e.g. the IBS Severity Scoring System), we calculated the standardized mean difference (SMD) and 95% CI in post-treatment scores between groups. Main results Seventeen RCTs (1806 participants) were included. Five RCTs compared acupuncture versus sham acupuncture. The risk of bias in these studies was low.We found no evidence of an improvement with acupuncture relative to sham (placebo) acupuncture for symptom severity (SMD-0.11, 95%CI −0.35 to 0.13; 4 RCTs; 281 patients) or quality of life (SMD = −0.03, 95%CI −0.27 to 0.22; 3 RCTs; 253 patients). Sensitivity analyses based on study

  16. Treatment of Irritability in Huntington’s Disease

    PubMed Central

    2010-01-01

    Opinion statement Irritability is a common neuropsychiatric feature of Huntington’s disease (HD), with prevalences varying from 38% to 73%. Similar prevalences of irritability are reported in other neurodegenerative disorders and traumatic brain injury, especially when the frontal lobe is involved. Before therapeutic interventions are initiated, the clinician should analyze the severity and frequency of the irritable behavior. By examining irritability in a broader spectrum, a tailor-made treatment can be provided. In general, I recommend as a first step a selective serotonin reuptake inhibitor (SSRI), such as sertraline, or the mood stabilizer valproate; they both have a mild side effect profile. Next, if the result is insufficient, I advise a switch between these two medications. As an alternative, I recommend a switch to a low dose of an atypical antipsychotic, preferably twice daily. Buspirone may be another alternative. Both antipsychotics and buspirone are also used as an add-on. Other mood stabilizers and beta-adrenergic receptor antagonists should only be used when earlier treatments are ineffective. The use of acetylcholinesterase inhibitors for the treatment of irritability is discouraged, as results are unclear. Synthetic cannabinoids are an interesting new therapeutic option, though their “illicit” compound and side effect profile make them not a first-line option. It is important to identify possible comorbid psychiatric disorders, because irritability may be secondary to a psychiatric condition, and the choice of medication partly depends on the co-occurrence of a specific psychiatric disorder. For example, antipsychotic medication would be the treatment of choice in delusional HD patients with excessive irritability, instead of an SSRI or valproate. Besides psychiatric comorbidity, the choice of medication also depends on the general medical condition, the side effect profile, and drug-drug interactions with other medications in concomitant use

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

    PubMed

    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. PMID:25252862

  18. Management of soft tissue irritation around exposed zygomatic implant in a hemimaxillectomy patient: a technical report.

    PubMed

    Balshi, Thomas J; Wolfinger, Glenn J; Balshi, Stephen F

    2015-01-01

    Patients missing portions or all of the maxillary alveolar bone who are restored with zygomatic implants frequently have threads exposed that can be a mucosal irritant. If such irritation is reported, covering the threads with a highly polished titanium sleeve is recommended. The technique of placing said custom sleeve is described. This adjunctive treatment method has eliminated mucosal irritation. PMID:25506639

  19. Newborn Irritability Moderates the Association between Infant Attachment Security and Toddler Exploration and Sociability

    ERIC Educational Resources Information Center

    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…

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

    PubMed

    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. PMID:19669895

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

    SciTech Connect

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

    2008-06-15

    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. Efficacy of skin barrier creams (II). Ineffectiveness of a popular "skin protector" against various irritants in the repetitive irritation test in the guinea pig.

    PubMed

    Frosch, P J; Schulze-Dirks, A; Hoffmann, M; Axthelm, I

    1993-08-01

    A popular "skin protector" consisting of an emulsion-like foam of lipophilic and hydrophilic substances (Marly skin) was evaluated in a previously described repetitive irritation guinea pig model. The product failed to inhibit the irritation due to sodium lauryl sulphate and toluene. In striking contrast to the recommended use, the irritant response of sodium hydroxide was aggravated, as demonstrated by significant differences for all test parameters (clinical score for erythema and scaling, transepidermal water loss, blood flow volume). The results show that protection against chemical irritants may be quite specific and that some formulations may actually be harmful. PMID:8365180

  3. New and emerging therapies for the treatment of irritable bowel syndrome: an update for gastroenterologists

    PubMed Central

    Foxx-Orenstein, Amy E.

    2016-01-01

    Irritable bowel syndrome is a functional bowel disorder with gastrointestinal symptoms (e.g. abdominal pain, straining, urgency, incomplete evacuation, nausea, and bloating) that occur alongside bowel function alterations (i.e. constipation, diarrhea, or both). Patients with irritable bowel syndrome may also experience comorbid anxiety and depression. Irritable bowel syndrome is common, with a prevalence estimated between 3% and 28%, affecting patient health and quality of life. Patients with moderate or severe irritable bowel syndrome generally seek medical care, whereas those with milder symptoms may choose self-management. Most patients with irritable bowel syndrome receive outpatient care, but irritable bowel syndrome-related hospitalizations do occur. The pathophysiology of irritable bowel syndrome is multifactorial (i.e. genetics, immune components, changes in the gut microbiota, disturbances in physiologic stress response systems, and psychosocial factors). Management of irritable bowel syndrome can include lifestyle changes, dietary interventions, counseling, psychologic medication, and agents that affect gastrointestinal motility. A number of therapies have emerged in recent years with clinical trial data demonstrating efficacy and safety for patients with irritable bowel syndrome, including agents that target gastrointestinal motility (i.e. linaclotide), gastrointestinal opioid receptors (i.e. asimadoline, eluxadoline), and gut microbiota (i.e. rifaximin). Linaclotide has been shown to significantly improve stool frequency and abdominal pain compared with placebo in constipation-predominant irritable bowel syndrome (number needed to treat, 5.1). Asimadoline shows efficacy in patients with moderate-to-severe irritable bowel syndrome-related pain. Rifaximin provided adequate relief of global irritable bowel syndrome symptoms versus placebo for a significantly greater percentage of patients with diarrhea-predominant irritable bowel syndrome (p < 0

  4. New and emerging therapies for the treatment of irritable bowel syndrome: an update for gastroenterologists.

    PubMed

    Foxx-Orenstein, Amy E

    2016-05-01

    Irritable bowel syndrome is a functional bowel disorder with gastrointestinal symptoms (e.g. abdominal pain, straining, urgency, incomplete evacuation, nausea, and bloating) that occur alongside bowel function alterations (i.e. constipation, diarrhea, or both). Patients with irritable bowel syndrome may also experience comorbid anxiety and depression. Irritable bowel syndrome is common, with a prevalence estimated between 3% and 28%, affecting patient health and quality of life. Patients with moderate or severe irritable bowel syndrome generally seek medical care, whereas those with milder symptoms may choose self-management. Most patients with irritable bowel syndrome receive outpatient care, but irritable bowel syndrome-related hospitalizations do occur. The pathophysiology of irritable bowel syndrome is multifactorial (i.e. genetics, immune components, changes in the gut microbiota, disturbances in physiologic stress response systems, and psychosocial factors). Management of irritable bowel syndrome can include lifestyle changes, dietary interventions, counseling, psychologic medication, and agents that affect gastrointestinal motility. A number of therapies have emerged in recent years with clinical trial data demonstrating efficacy and safety for patients with irritable bowel syndrome, including agents that target gastrointestinal motility (i.e. linaclotide), gastrointestinal opioid receptors (i.e. asimadoline, eluxadoline), and gut microbiota (i.e. rifaximin). Linaclotide has been shown to significantly improve stool frequency and abdominal pain compared with placebo in constipation-predominant irritable bowel syndrome (number needed to treat, 5.1). Asimadoline shows efficacy in patients with moderate-to-severe irritable bowel syndrome-related pain. Rifaximin provided adequate relief of global irritable bowel syndrome symptoms versus placebo for a significantly greater percentage of patients with diarrhea-predominant irritable bowel syndrome (p < 0

  5. Double blind study of ispaghula in irritable bowel syndrome.

    PubMed

    Prior, A; Whorwell, P J

    1987-11-01

    A double blind placebo controlled trial of ispaghula husk in 80 patients with irritable bowel syndrome is reported. Global assessment judged treatment to be satisfactory in 82% of patients receiving ispaghula and 53% of the placebo group (p less than 0.02). Bowel habit was unchanged in the placebo group, while constipation significantly improved in patients taking ispaghula (p = 0.026). Transit time decreased significantly in those taking ispaghula compared with placebo (p = 0.001), especially in patients with initially high transit times. Abdominal pain and bloating improved in both groups, with no significant differences between ispaghula and placebo. Four of the eight withdrawals on ispaghula and 10 of the 15 withdrawals on placebo were because of treatment failure. Ispaghula significantly improves overall well being in patients with irritable bowel syndrome, and in those with constipation favourably affects bowel habit and transit time. PMID:3322956

  6. Role of TNF-α polymorphism -308 in neurosensory irritation.

    PubMed

    Davis, J A; Visscher, M O; Wickett, R R; Hoath, S B

    2011-04-01

    Neurosensory cutaneous discomfort in response to topical products is common, yet the relationship between symptoms such as stinging and visible irritation is currently unclear. The presence of a polymorphism at position -308 on the TNF-α gene has been associated with skin irritation, i.e., erythema, dryness. Individuals with a G to A transition (AA/GA genotypes) have a lower threshold to experimentally induced irritation than those with the wild type (G allele, GG genotype). We investigated the effect of this polymorphism on neurosensory irritation (NSI). DNA genotyping was used to determine the allele type amongst a population of health care workers. The neurosensory response to lactic acid and water on the nasolabial folds and hands was assessed using a quantitative lactic acid sting test. Both genotypes had a more intense response to lactic acid compared with water on the face. The AA/GA genotypes had directionally higher scores from lactic acid (P = 0.1) and significantly higher stinging intensities from water (P = 0.001) on the face. For the hands, stinging intensities were higher for lactic acid and water amongst the AA/GA genotypes (P = 0.03 and 0.006 respectively). NSI to lactic acid was significantly higher on the face than on the hands (P < 0.05). Our findings indicate that subjects with the A transition at position -308 on the TNF-α gene experience more intense NSI with common ingredients, i.e., lactic acid and water, than those with the wild type. TNF-α polymorphism -308 may account for some of the inter-individual variability in response to skin care practices. PMID:20646084

  7. [NEWS IN ETIOLOGY AND PATHOGENESIS OF IRRITATED BOWEL SYNDROME].

    PubMed

    Sheptulin, A A; Vize-Khripunova, M A

    2016-01-01

    The concept of irritated bowel syndrome as a complex of functional disorders that can not be explained by organic changes and are totally due to intestinal motility and visceral sensitivity needs revision. The development of this syndrome also depends on a number of pathogenetic and etiological factors, such as inflammation of intestinal mucosa, changes of its permeability, previous infection, altered microflora, gene polymorphism, and food hypersensitivity. PMID:27459756

  8. Impact of psychological stress on irritable bowel syndrome

    PubMed Central

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

    2014-01-01

    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. PMID:25339801

  9. Impact of psychological stress on irritable bowel syndrome.

    PubMed

    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. PMID:25339801

  10. Complementary and alternative medicine for treatment of irritable bowel syndrome

    PubMed Central

    Shen, Yi-Hao A.; Nahas, Richard

    2009-01-01

    Abstract OBJECTIVE To review the evidence supporting selected complementary and alternative medicine approaches used in the treatment of irritable bowel syndrome (IBS). QUALITY OF EVIDENCE MEDLINE (from January 1966), EMBASE (from January 1980), and the Cochrane Database of Systematic Reviews were searched until March 2008, combining the terms irritable bowel syndrome or irritable colon with complementary therapies, alternative medicine, acupuncture, fiber, peppermint oil, herbal, traditional, yoga, massage, meditation, mind, relaxation, probiotic, hypnotherapy, psychotherapy, cognitive therapy, or behavior therapy. Results were screened to include only clinical trials, systematic reviews, and meta-analyses. Level I evidence was available for most interventions. MAIN MESSAGE Soluble fibre improves constipation and global IBS symptoms. Peppermint oil alleviates IBS symptoms, including abdominal pain. Probiotic trials show overall benefit for IBS but there is little evidence supporting the use of any specific strain. Hypnotherapy and cognitive-behavioural therapy are also effective therapeutic options for appropriate patients. Certain herbal formulas are supported by limited evidence, but safety is a potential concern. All interventions are supported by systematic reviews or meta-analyses. CONCLUSION Several complementary and alternative therapies can be recommended as part of an evidence-based approach to the treatment of IBS; these might provide patients with satisfactory relief and improve the therapeutic alliance. PMID:19221071

  11. Dissecting the role of TRPV1 in detecting multiple trigeminal irritants in three behavioral assays for sensory irritation

    PubMed Central

    Saunders, CJ

    2013-01-01

    Polymodal neurons of the trigeminal nerve innervate the nasal cavity, nasopharynx, oral cavity and cornea. Trigeminal nociceptive fibers express a diverse collection of receptors and are stimulated by a wide variety of chemicals. However, the mechanism of stimulation is known only for relatively few of these compounds. Capsaicin, for example, activates transient receptor potential vanilloid 1 (TRPV1) channels. In the present study, wildtype (C57Bl/6J) and TRPV1 knockout mice were tested in three behavioral assays for irritation to determine if TRPV1 is necessary to detect trigeminal irritants in addition to capsaicin. In one assay mice were presented with a chemical via a cotton swab and their response scored on a 5 level scale. In another assay, a modified two bottle preference test, which avoids the confound of mixing irritants with the animal’s drinking water, was used to assess aversion. In the final assay, an air dilution olfactometer was used to administer volatile compounds to mice restrained in a double-chambered plethysmograph where respiratory reflexes were monitored. TRPV1 knockouts showed deficiencies in the detection of benzaldehyde, cyclohexanone and eugenol in at least one assay. However, cyclohexanone was the only substance tested that appears to act solely through TRPV1. PMID:24358880

  12. Chronic, irritant contact dermatitis: Mechanisms, variables, and differentiation from other forms of contact dermatitis

    SciTech Connect

    Dahl, M.V. )

    1988-01-01

    Irritant dermatitis is an eczematous reaction to toxic chemicals contacting the skin. The mechanisms by which various chemicals elicit dermatitis are multiple. Strong irritants quickly elicit signs and symptoms of dermatitis, but weak irritants may not. Chronic cumulative exposure to weak irritants can elicit dermatitis which may mimic allergic contact dermatitis and mislead the physician and patient with respect to cause and preventative strategy. The skins of different people vary in susceptibilities to irritation. Susceptibility is also influenced by chemical properties, vehicles, concentrations, amounts applied to the skin surface, surface area, regional variations, length of exposure, method of exposure, age, sex, race, genetic background, environmental factors, hardening, concomitant disease, and the excited skin syndrome as well as treatment. Patch testing can help distinguish between allergens and irritants, but pitfalls may mislead.35 references.

  13. Response to Nonallergenic Irritants in Children With Allergic and Nonallergic Rhinitis

    PubMed Central

    Baek, Ji Hyeon; Cho, Eunhae; Kim, Mi Ae; Lee, Seung Won; Kang, Yu Sun; Sheen, Youn Ho; Jee, Hye Mi; Jung, Young-Ho

    2016-01-01

    Purpose Nonallergenic irritants can aggravate the symptoms of rhinitis. We investigated the clinical responses of children with allergic rhinitis (AR) and nonallergic rhinitis (NAR) to nonallergenic irritants, and identified factors associated with these responses. Methods Children with chronic rhinitis (n=208) were classified as having AR or NAR based on the presence of aeroallergen-specific IgE. Healthy controls (n=24) were recruited for comparison. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines were used to classify patients, and their irritant score (0-21 points) and current symptom score (5-35 points) were measured. Subjects with irritant scores ≥3 and <3 were classified as having irritant and nonirritant rhinitis, respectively. Results The mean age of enrolled subjects was 6.8 years (range: 1.8-16.0 years). The AR and NAR groups had similar irritant scores (P=0.394) and proportions of subjects with irritant scores ≥3 (P=0.105). Irritant score correlated positively with symptom score (P=0.005), and the proportion of subjects with irritant scores ≥3 was greater in children with moderate-severe rhinitis than in those with mild rhinitis (P=0.046). Multiple logistic regression analysis indicated that the presence of atopic eczema increased the risk for sensitivity to a nonallergenic irritant (aOR=2.928, 95% CI 1.567-5.473, P=0.001). Conclusions Response to a nonallergenic irritant was useful for gauging the severity of rhinitis, but not for differentiating AR from NAR. AR and NAR patients with atopic eczema may increase nasal sensitivity to nonallergenic irritants. PMID:27126728

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

    PubMed Central

    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

  15. Safety evaluation of petroleum products using an in vitro eye irritation test battery.

    PubMed

    Martin, S A; Roy, T A; Saladdin, K A; Fleming, B A; Mackerer, C R

    1994-08-01

    An in vitro eye irritation test battery (IVEye) composed of the EYTEX and Modified Agarose Diffusion Method (MADM) assays was evaluated for use as a predictive, economical screen and/or adjunct for the Draize eye test. EYTEX mimics corneal opacification using a synthetic matrix of proteins that is intended to produce measurable opacity on exposure to chemical irritants in proportion to their ocular irritation potential. MADM is a cytotoxicity-based assay consisting of NCTC clone 929 mouse fibroblasts overlayed with 1% agarose in culture medium. Potential eye irritation is measured macroscopically as the area of decolorization (neutral red release) around the area of chemical application and microscopically as the percentage of cell lysis resulting from chemical application. Of the 70 materials tested in the IVEye for which Draize eye test data also exist, the battery correctly identified 38 materials as non-irritants and 30 as irritants, with two false positives and no false negatives. Non-parametric analysis of the data show the battery to have a sensitivity of 100%, a specificity of 95% and a predictive value of 94%. The irritation class correlation (equivalence; irritation ranking) between EYTEX alone and the Draize data was 85%. These data support the use of IVEye as an accurate, reproducible and cost-effective in vitro method for identifying the eye irritation potential of petroleum products. PMID:20692994

  16. Lurasidone for the Treatment of Irritability Associated with Autistic Disorder.

    PubMed

    Loebel, Antony; Brams, Matthew; Goldman, Robert S; Silva, Robert; Hernandez, David; Deng, Ling; Mankoski, Raymond; Findling, Robert L

    2016-04-01

    The aim of this study was to evaluate the short-term efficacy and safety of lurasidone in treating irritability associated with autistic disorder. In this multicenter trial, outpatients age 6-17 years who met DSM-IV-TR criteria for autistic disorder, and who demonstrated irritability, agitation, and/or self-injurious behaviors were randomized to 6 weeks of double-blind treatment with lurasidone 20 mg/day (N = 50), 60 mg/day (N = 49), or placebo (N = 51). Efficacy measures included the Aberrant Behavior Checklist Irritability subscale (ABC-I, the primary endpoint) and the Clinical Global Impressions, Improvement (CGI-I) scale, and were analyzed using a likelihood-based mixed model for repeated measures. Least squares (LS) mean (standard error [SE]) improvement from baseline to Week 6 in the ABC-I was not significantly different for lurasidone 20 mg/day (-8.8 [1.5]) and lurasidone 60 mg/day (-9.4 [1.4]) versus placebo (-7.5 [1.5]; p = 0.55 and 0.36, respectively). CGI-I scores showed significantly greater LS mean [SE] improvement at Week 6 for lurasidone 20 mg/day versus placebo (2.8 [0.2] vs. 3.4 [0.2]; p = 0.035) but not for lurasidone 60 mg/day (3.1 [0.2]; p = 0.27). Discontinuation rates due to adverse events were: lurasidone 20 mg/day, 4.1 %; 60 mg/day, 3.9 %; and placebo, 8.2 %. Adverse events with an incidence ≥10 % (lurasidone combined, placebo) included vomiting (18.0, 4.1 %) and somnolence (12.0, 4.1 %). Modest changes were observed in weight and selected metabolic parameters. In this study, once-daily, fixed doses of 20 and 60 mg/day of lurasidone were not demonstrated to be efficacious compared to placebo for the short-term treatment of children and adolescents with moderate-to-severe irritability associated with autistic disorder. PMID:26659550

  17. Irritable bowel syndrome: a concise review of current treatment concepts.

    PubMed

    Wall, Geoffrey C; Bryant, Ginelle A; Bottenberg, Michelle M; Maki, Erik D; Miesner, Andrew R

    2014-07-21

    Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders causing patients to seek medical treatment. It is relatively resource intensive and the source of significant morbidity. Recent insights into the pathophysiology and treatment of IBS has given clinicians more options than ever to contend with this disorder. The purpose of our paper is to review older, "classic" treatments for IBS as well as newer agents and "alternative" therapies. We discuss the evidence base of these drugs and provide context to help develop appropriate treatment plans for IBS patients. PMID:25083054

  18. Irritable bowel syndrome: A concise review of current treatment concepts

    PubMed Central

    Wall, Geoffrey C; Bryant, Ginelle A; Bottenberg, Michelle M; Maki, Erik D; Miesner, Andrew R

    2014-01-01

    Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders causing patients to seek medical treatment. It is relatively resource intensive and the source of significant morbidity. Recent insights into the pathophysiology and treatment of IBS has given clinicians more options than ever to contend with this disorder. The purpose of our paper is to review older, “classic” treatments for IBS as well as newer agents and “alternative” therapies. We discuss the evidence base of these drugs and provide context to help develop appropriate treatment plans for IBS patients. PMID:25083054

  19. Gut Microbiota as Potential Orchestrators of Irritable Bowel Syndrome

    PubMed Central

    Bennet, Sean M.P.; Öhman, Lena; Simrén, Magnus

    2015-01-01

    Irritable bowel syndrome (IBS) is a multifactorial functional disorder with no clearly defined etiology or pathophysiology. Modern culture-independent techniques have improved the understanding of the gut microbiota’s composition and demonstrated that an altered gut microbiota profile might be found in at least some subgroups of IBS patients. Research on IBS from a microbial perspective is gaining momentum and advancing. This review will therefore highlight potential links between the gut microbiota and IBS by discussing the current knowledge of the gut microbiota; it will also illustrate bacterial-host interactions and how alterations to these interactions could exacerbate, induce or even help alleviate IBS. PMID:25918261

  20. Irritable bowel syndrome: a mild disorder; purely symptomatic treatment.

    PubMed

    2009-04-01

    (1) Patients frequently complain of occasional bowel movement disorders, associated with abdominal pain or discomfort, but they are rarely due to an underlying organ involvement. Even when patients have recurrent symptoms, serious disorders are no more frequent in these patients than in the general population, unless other manifestations, anaemia, or an inflammatory syndrome is also present; (2) There is currently no way of radically modifying the natural course of recurrent irritable bowel syndrome; (3) The effects of antispasmodics on abdominal pain have been tested in about 20 randomised controlled trials. Pinaverium and peppermint essential oil have the best-documented efficacy and only moderate adverse effects. Antispasmodics with marked atropinic effects do not have a favourable risk-benefit balance; (4) Tricylic antidepressants seem to have only modest analgesic effects in this setting. In contrast, their adverse effects are frequent and they have somewhat negative risk-benefit balances. Nor has the efficacy of selective serotonin reuptake inhibitor antidepressants (SSRIs) been demonstrated; (5) Alosetron and tegaserod carry a risk of potentially life-threatening adverse effects and therefore have negative risk-benefit balances; (6) Seeds of plants such as psyllium and ispaghul, as well as raw apples and pears, have a limited impact on constipation and pain. Osmotic laxatives are effective on constipation. Symptomatic treatments for constipation can sometimes aggravate abdominal discomfort; (7) Loperamide has been poorly assessed in patients with recurrent irritable bowel syndrome with diarrhoea. It modestly slows bowel movement but does not relieve pain or abdominal discomfort; (8) Dietary measures have not been tested in comparative trials. Some patients are convinced that certain foods provoke a recurrence of irritable bowel syndrome, but restrictive diets carry a risk of nutritional deficiencies; (9) Various techniques intended to control emotional and

  1. Traditional thoughts on the pathophysiology of irritable bowel syndrome.

    PubMed

    Hasler, William L

    2011-03-01

    The pathogenesis of symptoms in irritable bowel syndrome (IBS) is multifactorial and varies from patient to patient. Disturbances of motor function in the small intestine and colon and smooth-muscle dysfunction in other gut and extraintestinal regions are prominent. Abnormalities of sensory function in visceral and somatic structures are detected in most patients with IBS, which may relate to peripheral sensitization or altered central nervous system processing of afferent information. Contributions from psychosocial disturbances are observed in patients from tertiary centers and primary practice. Proof of causation of symptom genesis for most of these factors is limited. PMID:21333899

  2. Food: the forgotten factor in the irritable bowel syndrome.

    PubMed

    Eswaran, Shanti; Tack, Jan; Chey, William D

    2011-03-01

    After years of inattention, there is a growing body of evidence to suggest that dietary constituents at least exacerbate symptoms and perhaps contribute to the pathogenesis of the irritable bowel syndrome (IBS). Although patients with IBS self-report food allergies more often than the general population, the evidence suggests that true food allergies are relatively uncommon. Less clearly defined food intolerances may be an important contributor to symptoms in IBS patients. This article reviews the literature supporting a causal link between food and the symptoms of IBS as well as the evidence supporting dietary interventions as a means of managing IBS symptoms. PMID:21333905

  3. Gut microbiota as potential orchestrators of irritable bowel syndrome.

    PubMed

    Bennet, Sean M P; Ohman, Lena; Simren, Magnus

    2015-05-23

    Irritable bowel syndrome (IBS) is a multifactorial functional disorder with no clearly defined etiology or pathophysiology. Modern culture-independent techniques have improved the understanding of the gut microbiota's composition and demonstrated that an altered gut microbiota profile might be found in at least some subgroups of IBS patients. Research on IBS from a microbial perspective is gaining momentum and advancing. This review will therefore highlight potential links between the gut microbiota and IBS by discussing the current knowledge of the gut microbiota; it will also illustrate bacterial-host interactions and how alterations to these interactions could exacerbate, induce or even help alleviate IBS. PMID:25918261

  4. When to reconsider the diagnosis of irritable bowel syndrome.

    PubMed

    Hammerle, Christopher W; Crowe, Sheila E

    2011-06-01

    Irritable bowel syndrome (IBS) is a highly prevalent disorder characterized by nonspecific symptoms that can mimic other common medical conditions. A careful history and physical examination may reveal clues that suggest a coexisting or alternative diagnosis, such as small intestinal bacterial overgrowth or celiac disease (CD). Testing for bacterial overgrowth has limitations, but emerging data suggest that antibiotics may be of some benefit in patients with IBS with diarrhea and bloating. CD seems to have a higher prevalence in patients with IBS. Some patients with IBS may have symptomatic improvement on gluten-restricted diets, without histologic or serologic evidence of CD. PMID:21601781

  5. [Treatment of irritable bowel syndrome with dicetelium and spasmomen].

    PubMed

    Nedogoda, S V; Parshev, V V

    2000-01-01

    The aim of the study was to compare clinical efficacy of new spasmolytics--pinaverium bromide (dicetel, Solvay Pharma) and otilonium bromide (spasmomen, Menarini-Berlin-Chemie)--in the treatment of irritable bowel syndrome. Effects appearing during the treatment with anxiolytic drug tofisopam (grandaxin, Egis) after using dicetel and spasmomen were also studied. The results indicate marked clinical efficiency of dicetel and spasmomen which improve vegetative functions and psychoemotional status. Grandaxin provides further improvement of clinical symptoms and additionally corrects psychoemotional status. PMID:11220900

  6. Underlying molecular and cellular mechanisms in childhood irritable bowel syndrome.

    PubMed

    Chumpitazi, Bruno P; Shulman, Robert J

    2016-12-01

    Irritable bowel syndrome (IBS) affects a large number of children throughout the world. The symptom expression of IBS is heterogeneous, and several factors which may be interrelated within the IBS biopsychosocial model play a role. These factors include visceral hyperalgesia, intestinal permeability, gut microbiota, psychosocial distress, gut inflammation, bile acids, food intolerance, colonic bacterial fermentation, and genetics. The molecular and cellular mechanisms of these factors are being actively investigated. In this mini-review, we present updates of these mechanisms and, where possible, relate the findings to childhood IBS. Mechanistic elucidation may lead to the identification of biomarkers as well as personalized childhood IBS therapies. PMID:26883355

  7. Irritable bowel syndrome. Strategy for the family physician.

    PubMed Central

    Thompson, W. G.

    1994-01-01

    Irritable bowel syndrome is one of the most common reasons for disability and health care seeking. A sensible strategy for management incorporates a confident diagnosis based upon history, physical examination, and pertinent tests. The physician can then reassure the patient, offer dietary and stress management advice, and recommend bran to relieve constipation and to evoke the placebo response. Patients who do not respond could require supportive psychotherapy or a drug for the dominant symptom. A few require careful referral, but overall responsibility should remain with the primary physician. Images Figures 1-2 PMID:8130678

  8. Amantadine Effect on Perceptions of Irritability after Traumatic Brain Injury: Results of the Amantadine Irritability Multisite Study

    PubMed Central

    Sherer, Mark; Malec, James F.; Zafonte, Ross D.; Whitney, Marybeth; Bell, Kathleen; Dikmen, Sureyya; Bogner, Jennifer; Mysiw, Jerry; Pershad, Rashmi

    2015-01-01

    Abstract This study examines the effect of amantadine on irritability in persons in the post-acute period after traumatic brain injury (TBI). There were 168 persons ≥6 months post-TBI with irritability who were enrolled in a parallel-group, randomized, double-blind, placebo-controlled trial receiving either amantadine 100 mg twice daily or equivalent placebo for 60 days. Subjects were assessed at baseline and days 28 (primary end-point) and 60 of treatment using observer-rated and participant-rated Neuropsychiatric Inventory (NPI-I) Most Problematic item (primary outcome), NPI Most Aberrant item, and NPI-I Distress Scores, as well as physician-rated Clinical Global Impressions (CGI) scale. Observer ratings between the two groups were not statistically significantly different at day 28 or 60; however, observers rated the majority in both groups as having improved at both intervals. Participant ratings for day 60 demonstrated improvements in both groups with greater improvement in the amantadine group on NPI-I Most Problematic (p<0.04) and NPI-I Distress (p<0.04). These results were not significant with correction for multiple comparisons. CGI demonstrated greater improvement for amantadine than the placebo group (p<0.04). Adverse event occurrence did not differ between the two groups. While observers in both groups reported large improvements, significant group differences were not found for the primary outcome (observer ratings) at either day 28 or 60. This large placebo or nonspecific effect may have masked detection of a treatment effect. The result of this study of amantadine 100 mg every morning and noon to reduce irritability was not positive from the observer perspective, although there are indications of improvement at day 60 from the perspective of persons with TBI and clinicians that may warrant further investigation. PMID:25774566

  9. Methylglyoxal Induces Systemic Symptoms of Irritable Bowel Syndrome

    PubMed Central

    Zhang, Shuang; Jiao, Taiwei; Chen, Yushuai; Gao, Nan; Zhang, Lili; Jiang, Min

    2014-01-01

    Patients with irritable bowel syndrome (IBS) show a wide range of symptoms including diarrhea, abdominal pain, changes in bowel habits, nausea, vomiting, headache, anxiety, depression and cognitive impairment. Methylglyoxal has been proved to be a potential toxic metabolite produced by intestinal bacteria. The present study was aimed at investigating the correlation between methylglyoxal and irritable bowel syndrome. Rats were treated with an enema infusion of methylglyoxal. Fecal water content, visceral sensitivity, behavioral tests and serum 5-hydroxytryptamine (5-HT) were assessed after methylglyoxal exposure. Our data showed that fecal water content was significantly higher than controls after methylglyoxal exposure except that of 30 mM group. Threshold volumes on balloon distension decreased in the treatment groups. All exposed rats showed obvious head scratching and grooming behavior and a decrease in sucrose preference. The serum 5-HT values were increased in 30, 60, 90 mM groups and decreased in 150 mM group. Our findings suggested that methylglyoxal could induce diarrhea, visceral hypersensitivity, headache as well as depression-like behaviors in rats, and might be the key role in triggering systemic symptoms of IBS. PMID:25157984

  10. Sensitization of the Trigeminovascular System following Environmental Irritant Exposure

    PubMed Central

    Kunkler, Phillip Edward; Zhang, LuJuan; Pellman, Jessica Joan; Oxford, Gerry Stephen; Hurley, Joyce Harts

    2016-01-01

    Background Air pollution is linked to increased emergency room visits for headache and migraine patients frequently cite chemicals or odors as headache triggers, but the association between air pollutants and headache is not well-understood. We previously reported that nasal administration of environmental irritants acutely increases meningeal blood flow via a TRPA1-dependent mechanism, involving the trigeminovascular system. Here, we examine whether chronic environmental irritant exposure sensitizes the trigeminovascular system. Methods Male rats were exposed to acrolein, a TRPA1 agonist, or room air by inhalation for 4 days prior to meningeal blood flow measurements. Some animals were injected daily with a TRPA1 antagonist, AP-18 or vehicle prior to inhalation exposure. Trigeminal ganglia were isolated following blood flow measurements for immunocytochemistry and/or qPCR determination of TRPV1, TRPA1 and CGRP levels. Results Acrolein inhalation exposure potentiated blood flow responses to both TRPA1 and TRPV1 agonists compared to room air. Acrolein exposure did not alter TRPV1 or TRPA1 mRNA levels or TRPV1 or CGRP immunoreactive cell counts in the trigeminal ganglion. Acrolein sensitization of trigeminovascular responses to a TRPA1 agonist was attenuated by pre-treatment with AP-18. Interpretation These results suggest trigeminovascular sensitization as a mechanism for enhanced headache susceptibility after chemical exposure. PMID:25724913

  11. Role of FODMAPs in Patients With Irritable Bowel Syndrome.

    PubMed

    Mansueto, Pasquale; Seidita, Aurelio; D'Alcamo, Alberto; Carroccio, Antonio

    2015-10-01

    Irritable bowel syndrome (IBS) is a condition characterized by abdominal pain, bloating, flatus, and altered bowel habits. The role of dietary components in inducing IBS symptoms is difficult to explore. To date, foods are not considered a cause but rather symptom-triggering factors. Particular interest has been given to the so-called FODMAPs (fermentable oligo-, di-, and monosaccharides and polyols). We aimed to summarize the evidence from the most common approaches to manage suspected food intolerance in IBS, with a particular interest in the role of FODMAPs and the effects of a low FODMAP diet. We reviewed literature, consulting PubMed and Medline by using the search terms FODMAP(s), fructose, lactose, fructans, galactans, polyols (sorbitol, mannitol, maltitol, xylitol, erythritol, polydextrose, and isomalt), irritable bowel syndrome, and functional gastrointestinal symptoms. FODMAP-restricted diets have been used for a long time to manage patients with IBS. The innovation in the so-called FODMAP concept is that a global restriction should have a more consistent effect than a limited one in preventing abdominal distension. Even though all the potential low FODMAP diets provide good relief of symptoms in many patients, there is just a little relief in others. Several studies highlight the role of low FODMAP diets to improve symptoms in patients with IBS. The evidence on this dietary approach supports the hypothesis that a low FODMAP diet should be the first dietary approach. However, many points remain to be clarified, including the evaluation of possibly significant nutrition concerns. PMID:25694210

  12. Methylglyoxal induces systemic symptoms of irritable bowel syndrome.

    PubMed

    Zhang, Shuang; Jiao, Taiwei; Chen, Yushuai; Gao, Nan; Zhang, Lili; Jiang, Min

    2014-01-01

    Patients with irritable bowel syndrome (IBS) show a wide range of symptoms including diarrhea, abdominal pain, changes in bowel habits, nausea, vomiting, headache, anxiety, depression and cognitive impairment. Methylglyoxal has been proved to be a potential toxic metabolite produced by intestinal bacteria. The present study was aimed at investigating the correlation between methylglyoxal and irritable bowel syndrome. Rats were treated with an enema infusion of methylglyoxal. Fecal water content, visceral sensitivity, behavioral tests and serum 5-hydroxytryptamine (5-HT) were assessed after methylglyoxal exposure. Our data showed that fecal water content was significantly higher than controls after methylglyoxal exposure except that of 30 mM group. Threshold volumes on balloon distension decreased in the treatment groups. All exposed rats showed obvious head scratching and grooming behavior and a decrease in sucrose preference. The serum 5-HT values were increased in 30, 60, 90 mM groups and decreased in 150 mM group. Our findings suggested that methylglyoxal could induce diarrhea, visceral hypersensitivity, headache as well as depression-like behaviors in rats, and might be the key role in triggering systemic symptoms of IBS. PMID:25157984

  13. [Rectoscopy and Hemoccult II in irritable colon. A prospective study].

    PubMed

    Hovendal, C P; Kronborg, O; Hem, J; Grinsted, P; Fenger, C

    1990-09-17

    It was investigated whether Hemoccult-II test (H-II) could reduce the number of colonic examinations in patients with the irritable bowel syndrome, with normal rigid proctoscopic findings. A negative H-II was obtained in 299 patients from general practice and a positive test in nine. Colonoscopy was done in 157 and double contrast barium enema in 142 after random allocation. The nine patients with positive H-II all had colonoscopy. Among the 299 with negative H-II, colonic adenomas were detected in ten and an early cancer in an adenoma in the sigmoid colon; overlooked rectal adenomas were found in three, rectal cancer in one, rectal carcinoid in another and a coecal cancer, which could be palpated, in a third patient. Two patients with colonic cancer and one with adenoma were detected among those with positive H-II. All patients were followed by clinical examination after one year. In conclusion, colonic examination should carry a low priority in patients with symptoms of irritable bowel, negative Hemoccult-II and normal rigid proctoscopic findings performed by an experienced examiner. The investigation confirmed the recommendation of total colonoscopy in patients with a positive H-II and added support for increasing number of endoscopy services in contrast to those of diagnostic radiology, which should be reduced. PMID:2219505

  14. Pathologic response of the lung to irritant gases

    SciTech Connect

    Robinson, F.R.; Runnels, L.J.; Conrad, D.A.; Teclaw, R.F.; Thacker, H.L. )

    1990-12-01

    The pathologic response of the lung to irritant gases ranges from the acute exudative phase through the subacute proliferative phase to the chronic fibrosing phase. These responses are based on damage to the Type I cells, and possibly endothelial cells, and the subsequent proliferative and repair processes in the surviving animals. Responses to high dose exposures appear at the microscopic level as exudation of protein rich fluids into alveoli (alveolar edema) and subsequent death due to anoxia. Physiologically, this could be described as a mismatch of ventilation with perfusion, resulting in impaired gas exchange. Animals surviving this acute exudative phase resolve the alveolar edema to fibrin, and Type II cells become hypertrophic and hyperplastic in the process of replacing the damaged Type I cells. The acute and subacute responses also elicit inflammatory changes in the interstitium of the lung that may progress to fibrosis in the chronic stage of a survivable exposure. Diagnostic cases in livestock involving irritant gases reflect similar toxic injuries to the lung.

  15. [Manometric effects of pinaverium bromide in irritable bowel syndrome].

    PubMed

    Soifer, L; Varela, E; Olmos, J

    1992-01-01

    The effects of pinaverium bromide on colonic motility were investigated in a controlled, controlled, cross-over study in 32 patients with irritable bowel syndrome. Constipation was clearly predominant in one group of 16 patients, and diarrhea in the other group of 16. Manometric measurements were taken of the colonic motor response generated by distention of a balloon inserted to the rectosigmoid junction. Measurements were taken before and one hour after ingestion of two tablets containing placebo or two tablets each containing 50 mg of pinaverium bromide. Following intake of placebo the motility index increased from the basal value in patients with constipation, and resistance to distention decreased in the diarrhea group. These changes were attributable to repetition of the mechanical stimulus within a relatively brief time lapse, or more probably to the ingestion of liquid which accompanied intake of tablets. Compared with placebo, pinaverium bromide induced inhibition of both effects. From the therapeutic point of view, the decrease in motility index seen in patients with irritable bowel syndrome and constipation is particularly interesting. PMID:1295286

  16. A superfusion apparatus for ex vivo human eye irritation investigations.

    PubMed

    Elbadawy, Hossein Mostafa; Salvalaio, Gianni; Parekh, Mohit; Ruzza, Alessandro; Baruzzo, Mattia; Cagini, Carlo; Ponzin, Diego; Ferrari, Stefano

    2015-10-01

    A superfusion apparatus (SA) was developed to maintain isolated human corneas ex vivo under conditions which mimic the natural eye environment in vivo, including controlled temperature, tear flow and intraocular pressure. The SA was designed, developed and tested for use in ophthalmic pre-clinical research and to test new pharmaceutical formulations. Corneas undergo an equilibration process in the new physiological environment for one day. The test was then initiated by the application of the test substance, incubation, and temporal assessment of corneal damage using various parameters. The effects of mild and severe irritant concentrations of NaOH (2% and 8%, respectively) on corneal opacity, swelling and epithelial integrity were studied, and the inflammatory status assessed using F4/80 and MPO as macrophages and neutrophils markers, respectively. The SA was then used to test new artificial tear formulations supplemented with silver ions as an active constituent, showing different degrees of inflammatory responses as indicated by the migration of MPO and F4/80 positive cells towards the epithelium. The human cornea superfusion apparatus was proposed as a model for acute eye irritation research. PMID:26100225

  17. Skin reactions and irritation potential of four commercial toothpastes.

    PubMed

    Skaare, A; Kjaerheim, V; Barkvoll, P; Rølla, G

    1997-04-01

    Skin reactions to 4 toothpastes were tested in 19 healthy dental students in a double-blind study. The hypothesis was that common toothpaste brands with and without sodium lauryl sulfate (SLS) and triclosan and with different additives/emulgators differ in irritation potential. An occlusion test system on human skin was used. The toothpastes tested were A) Zendium (non-ionic detergent), B) Solidox F (SLS/polyethylene glycol), C) Colgate Total (triclosan/copolymer/SLS/propylene glycol), and D) Solidox G (triclosan/zinc citrate/SLS/polyethylene glycol). Toothpaste C was the greatest irritant, causing skin erythema in 16 of the 19 subjects, whereas toothpaste D gave no reactions. Toothpaste B provoked three reactions (two severe), whereas toothpaste A caused only one mild reaction. Although this study was carried out on skin and hence not directly applicable to the oral cavity, these and previous results may indicate that a toothpaste without propylene glycol and SLS may be preferred by susceptible persons. PMID:9176662

  18. Irritable bowel syndrome: a test of the colonic hyperalgesia hypothesis.

    PubMed

    Latimer, P; Campbell, D; Latimer, M; Sarna, S; Daniel, E; Waterfall, W

    1979-09-01

    This study tested the hypothesis that, patients with irritable bowel syndrome (IBS), there is a primary hyperalgesia of the colon. Previous work, which examined these patients and normals, has not included subjects who provide a control for relevant psychological characteristics. We compared ratings of pain, following varying degrees of distension of the sigmoid colon, in normals, patients with IBS, and patients who were psychologically disturbed but without bowel symptoms. Psychological characteristics were assessed by a psychiatric interview and psychometric inventories; response to distension was tested by placing a tube in the rectosigmoid colon and successively inflating a nd deflating a balloon at its tip at 10 cm3 increments up to 50 cm3. Ratings of pain were recorded at each volume. The results indicated that the two patient groups were psychologically similar and both were more disturbed than normals. A linear relation was found between reports of pain and volume of distension in all three groups. There were no significant differences between the proportions of subjects experiencing pain in each group or the average of the ratings. There were no significant associations between the pain ratings and measures of anxiety, depression, neuroticism, and extraversion. The data do not support the hypothesis that colonic hyperalgesia is an important contributory factor in the etiology of the irritable bowel syndrome. PMID:537039

  19. Managing Irritability and Aggression in Autism Spectrum Disorders in Children and Adolescents

    ERIC Educational Resources Information Center

    Robb, Adelaide S.

    2010-01-01

    Children with autism and autism spectrum disorders have a high rate of irritability and aggressive symptoms. In one study up to 20% of children with autism have symptoms of irritability and aggression including aggression, severe tantrums, and deliberate self injurious behavior (Lecavalier [2006] "J. Autism Dev. Disord." 36:1101-1114.). These…

  20. Efficacy of 4 commercially available protective creams in the repetitive irritation test (RIT).

    PubMed

    Schlüter-Wigger, W; Elsner, P

    1996-04-01

    Protective creams (PCs) play their part in the prevention of occupational contact dermatitis, even though efficacy data are frequently lacking. 4 different commercially-available PCs were evaluated against a set of 4 standard irritants (10% sodium lauryl sulfate (SLS), 1% sodium hydroxide (NaOH), 30% lactic acid (LA) and undiluted toluene (TOL)) in the repetitive irritation test (RIT) in humans described by Frosch and Kurte. 20 subjects were tested on the paravertebral skin on the mid-back. Irritation was assessed by visual scoring, transepidermal water loss (TEWL) as an indicator of epidermal barrier function, and colorimetry as a parameter of inflammation. Very different protective effects of the PCs on irritation by chemical substances were detectable. All products were very effective against SLS irritation. No PC provided significant protection against toluene. 3 products showed a partially protective effect against all ionic irritants, while the 4th showed less protection against SLS and NaOH, and even amplification of inflammation by TOL. Considering the range of PC effects from good protection to increased irritation, depending on the irritant, the need for careful selection of PCs for specific workplaces is stressed. PMID:8730167

  1. AGONISTIC SENSORY EFFECTS OF AIRBORNE CHEMICALS IN MIXTURES: ODOR, NASAL PUNGENCY, AND EYE IRRITATION

    EPA Science Inventory

    Threshold responses of odor, nasal pungency (irritation), and eye irritation were measured for single chemicals (1-propanol, 1-hexanol, ethyl acetate, heptyl acetate, 2-pentanone, 2-heptanone, toluene, ethyl benzene, and propyl benzene) and mixtures of them (two three-component m...

  2. EFFECTS OF FLY ASH AND ITS CONSTITUENTS ON SENSORY IRRITATION IN MICE

    EPA Science Inventory

    Sensory irritation caused by fly ash from oil-fired (OF), fluidized bed coal (FB) combustion and conventional coal (CC) combustion power plants, and from Mt. St. Helens volcano (VA) was studied in mice. The irritating sensation due to contact with fly ash or its constituents was ...

  3. POST-INFECTIOUS IRRITABLE BOWEL SYNDROME: A LONG TERM CONSEQUENCE OF BACTERIAL GASTROENTERITIS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Irritable bowel syndrome (IBS) is a commonly diagnosed disease characterized by gastrointestinal symptoms often associated with psychological illness and emotional problems. The prevalence rate world-wide for IBS ranges from 10 to 20% and is higher for women than for men. Irritable bowel disease ...

  4. Tandem repeated application of organic solvents and sodium lauryl sulphate enhances cumulative skin irritation.

    PubMed

    Schliemann, Sibylle; Schmidt, Christina; Elsner, Peter

    2014-01-01

    The objective of our study was to investigate the tandem irritation potential of two organic solvents with concurrent exposure to the hydrophilic detergent irritant sodium lauryl sulphate (SLS). A tandem repeated irritation test was performed with two undiluted organic solvents, cumene (C) and octane (O), with either alternating application with SLS 0.5% or twice daily application of each irritant alone in 27 volunteers on the skin of the back. The cumulative irritation induced over 4 days was quantified using visual scoring and non-invasive bioengineering measurements (skin colour reflectance, skin hydration and transepidermal water loss). Repeated application of C/SLS and O/SLS induced more decline of stratum corneum hydration and higher degrees of clinical irritation and erythema compared to each irritant alone. Our results demonstrate a further example of additive harmful skin effects induced by particular skin irritants and indicate that exposure to organic solvents together with detergents may increase the risk of acquiring occupational contact dermatitis. PMID:24457469

  5. Irritability without Elation in a Large Bipolar Youth Sample: Frequency and Clinical Description

    ERIC Educational Resources Information Center

    Hunt, Jeffrey; Birmaher, Boris; Leonard, Henrietta; Strober, Michael; Axelson, David; Ryan, Neal; Yang, Mei; Gill, Marykay; Dyl, Jennifer; Esposito-Smythers, Christianne; Swenson, Lance; Goldstein, Benjamin; Goldstein, Tina; Stout, Robert; Keller, Martin

    2009-01-01

    The assessment of 361 youths with bipolar disorder reveal that irritable-only subgroups constitute 10 percent of this sample while elated-only subgroups constitute 15 percent of the sample. These findings support continued consideration for episodic irritability in the diagnosis of pediatric bipolar disorder.

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

    PubMed Central

    Lee, Sang Shin; 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 questionnaire sheet assessing the extent of histrionic personality traits, extraversion-introversion, and current psychological status. The present authors also collected basic sociodemographic data including alcohol use history. Results. A total of 32 irritable patients and 32 stable patients were analyzed. The histrionic personality trait score of the irritable group was higher than that of the stable group (9.5 ± 3.1 versus 6.9 ± 2.9; P = 0.001), as was the anxiety score (52.8 ± 8.6 versus 46.1 ± 9.6; P = 0.004). Heavy alcohol use was more frequently observed in the irritable group (65.6% versus 28.1%; P = 0.003). In multivariate analysis, all these three factors were independently correlated with irritability during CSE. Conclusion. This study revealed that histrionic personality traits, anxiety, and heavy alcohol use can affect irritability during CSE. PMID:25954307

  7. [Controlled clinical study of the action of mebeverine hydrochloride in the treatment of irritable colon].

    PubMed

    Secco, G B; Di Somma, C; Arnulfo, G; Ricci, C

    1983-03-31

    The results of a study about the mebeverina administered in 45 cases of irritable colon are reported. The clinical and laboratory findings together with the results of colometrography under psychic stimulation, have shown the therapeutic efficacy of the new formulation, specially in irritable colon with abdominal pain. Its tolerance was excellent. PMID:6339996

  8. A single exposure to photochemical smog causes airway irritation and cardiac dysrhythmia in mice

    EPA Science Inventory

    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. Evaluation of the EYTEX system as a screen for eye irritancy of petroleum products.

    PubMed

    Roy, T A; Saladdin, K A; Mackerer, C R

    1994-08-01

    89 petroleum products were tested in the EYTEX in vitro assay and the results were compared with data from Draize tests on the same materials. All 26 chemicals assessed as irritant in the Draize test were classified as irritant by the EYTEX assay; 61 of the 63 non-irritants were correctly classified by the in vitro assay. The correlation between the results from the EYTEX system and the Draize data was 89%, and the predictive value of the EYTEX system (percentage of EYTEX irritants that are true irritants) was 93%. When the same chemicals were tested in another laboratory, the coefficient of determination for the comparison of the EYTEX scores from the two laboratories was R(2) = 0.86. The results demonstrate the reliability and interpretability of the EYTEX assay carried out in our laboratory and therefore the viability, if not the validity, of this in vitro method as a screening test for the Draize assay. PMID:20693014

  10. New model of cytoprotection/adaptive cytoprotection in rats: endogenous small irritants, antiulcer agents and indomethacin.

    PubMed

    Sikirić, P; Seiwerth, S; Desković, S; Grabarević, Z; Marović, A; Rucman, R; Petek, M; Konjevoda, P; Jadrijević, S; Sosa, T; Perović, D; Aralica, G; Turković, B

    1999-01-01

    Adaptive cytoprotection in the stomach was originally defined by applying the exogenous irritants only. The contribution of endogenous irritants as inductors of initial lesions was not specially evaluated. No attempt was made to either focus antiulcer agent activity on adaptive cytoprotection, or split their 'cytoprotection' into complex adaptive cytoprotective activity and simple cytoprotective effects. Agents had so far not been applied simultaneously with the second challenge with ethanol (or irritant), when differences between cytoprotection and adaptive cytoprotection appear. Gastrojejunal anastomosis for 24 h in rats was introduced as new model for analyzing cytoprotection/adaptive cytoprotection. The contribution of the up-normal level of endogenous irritants and the endogenous small irritant-induced minor lesions during the adaptive cytoprotection were studied. The effect of late challenge with 96% ethanol in the presence of an up-normal level of endogenous irritants and endogenous small irritant-induced minor lesions was compared with results of classic studies of ethanol-induced gastric lesions in normal rats (1 ml/rat i.g.). Antiulcer agents or a prostaglandins-synthesis inhibitor, indomethacin, given once only in classic studies, were given at several points during injury induction: (i) surgery, (ii) mild ethanol, (iii) strong ethanol, (iv) strong ethanol applied after a suitable period following either mild ethanol or surgery). Their effects were compared in rats treated as follows: exogenous irritant studies (96% or 20% ethanol), exogenous/exogenous irritant studies (20% ethanol 1 h before 96% ethanol), endogenous irritant studies (gastrojejunal anastomosis for 24 h), and endogenous/exogenous irritant studies (gastrojejunal anastomosis for 24 h before 96% ethanol). Characteristic of the various irritants differed: the (preceding) small irritants (exogenous (i.e., mild ethanol in healthy intact rats) (exogenous irritant studies) vs. endogenous (e

  11. Quaternary ammonium derivatives as spasmolytics for irritable bowel syndrome.

    PubMed

    Evangelista, S

    2004-01-01

    Quaternary ammonium derivatives such as cimetropium, n-butyl scopolammonium, otilonium and pinaverium bromide have been discovered and developed as potent spasmolytics of the gastrointestinal tract. Their pharmacological activity has been proven in both "in vivo" and "in vitro" studies of hypermotility. "In vitro" experiments showed that they possess antimuscarinic activity at nM level but only pinaverium and otilonium are endowed with calcium channel blocker properties. These latter compounds relaxed the gastrointestinal smooth muscle mainly through a specific inhibition of calcium ion influx through L-type voltage operated calcium channels. Molecular pharmacology trials have indicated that pinaverium and otilonium can bind specific subunits of the calcium channel in the external surface of the plasma membrane and in this way they block the machinery of the contraction. Recent evidence showed that otilonium is able to bind tachykinin NK(2) receptors and not only inhibits one of the major contractile agents but can reduce the activation of afferent nerves devoted to the passage of sensory signals from the periphery to the central nervous system. Thanks to their typical physico-chemical characteristics, they are poorly absorbed by the systemic circulation and generally remain in the gastrointestinal tract where they exert the muscle relaxant activity by a local activity. Some differences exists in the absorption among these compounds: both n-butyl scopolammonium and cimetropium are partially taken up in the bloodstream, pinaverium has a low absorption (8-10 %) but is endowed with an excellent hepato-biliary excretion and otilonium, which has the lowest absorption (3 %), is almost totally excreted by faeces. Quaternary ammonium derivatives are widely used for the treatment of irritable bowel syndrome and recent meta-analyses have supported their efficacy in this disease. Due to its therapeutic index, the use of n-butyl scopolammonium is more indicated to treat acute

  12. Medical Movies on the Web Debuts with Gene Kelly's "Combat Fatigue Irritability" 1945 Film | NIH MedlinePlus the ...

    MedlinePlus

    ... Debuts with Gene Kelly's "Combat Fatigue Irritability" 1945 Film Past Issues / Spring 2014 Table of Contents Actor Gene Kelly in the 1945 film, Combat Fatigue Irritability, now available to the public ...

  13. An evaluation of irritant smoke to detect exhalation valve leakage in respirators.

    PubMed

    Snyder, Erin M; McKay, Roy T

    2003-09-01

    This study evaluated the ability of a qualitative fit-test method (irritant smoke) to detect known exhalation valve leakage. The OSHA protocol for the irritant smoke test mandates the use of a low flow air pump at 200 mL/minute or an aspirator squeeze bulb. Many commercial test kits include an aspirator bulb, which is subject to variation in frequency, depth of squeeze, fatigue rate, and individual hand strength. Previous studies on irritant smoke used a handheld squeeze bulb. This study evaluated the effectiveness of a low flow pump for irritant smoke fit-testing. Twenty subjects wearing North 7600 series full-face respirators equipped with P100 filters were fit-tested with a Portacount Plus to ensure adequate fit. After successful fit was demonstrated, the exhalation valve was replaced with a damaged valve and/or rotated approximately 90 degrees to produce a fit factor below 100. Having induced an exhalation valve leak, the irritant smoke fit-test was performed using the OSHA irritant smoke protocol. To avoid introducing additional unknown leakage, all head movement exercises were replaced with the head straight, normal breathing maneuver. Irritant smoke did not detect 40 percent of respirators with leaking exhalation valves. Sixty percent of the subjects were able to detect the irritant smoke. Test sensitivity was 60 percent, well below the recommended 95 percent criterion. Of the 12 subjects that detected irritant smoke, none detected the smoke in less than a minute; the average detection time was 3 min 5 s. Some subjects were able to suppress the cough reflex. These findings suggest that qualitative fit-testing using irritant smoke with a 200 ml/min continuous flow pump does not have adequate sensitivity to detect fit factors less than 100. PMID:12909538

  14. Rifaximin in irritable bowel syndrome: rationale, evidence and clinical use.

    PubMed

    Saadi, Mohammed; McCallum, Richard W

    2013-03-01

    Irritable bowel syndrome (IBS) is the most common functional bowel disease that affects up to 15% of the US population. The majority of patients with IBS have significant bloating and gas. Recent evidence is beginning to suggest that patients with IBS may have an alteration in the gastrointestinal flora. Specifically, findings suggest that patients with IBS have excessive bacteria in the small bowel, referred to as bacterial overgrowth. Therefore there may be benefits of antibiotic-based therapies for IBS. Rifaximin is a nonabsorbable antibiotic that demonstrates no clinically relevant bacterial resistance. Some studies have demonstrated the efficacy and durable improvement of IBS symptoms after treatment with rifaximin. In this review we explore the current data showing the association of small intestinal bacterial overgrowth (SIBO) and IBS as well as review the available data on the clinical use of rifaximin in the treatment of SIBO in patients with IBS. PMID:23556126

  15. Rifaximin in irritable bowel syndrome: rationale, evidence and clinical use

    PubMed Central

    Saadi, Mohammed

    2013-01-01

    Irritable bowel syndrome (IBS) is the most common functional bowel disease that affects up to 15% of the US population. The majority of patients with IBS have significant bloating and gas. Recent evidence is beginning to suggest that patients with IBS may have an alteration in the gastrointestinal flora. Specifically, findings suggest that patients with IBS have excessive bacteria in the small bowel, referred to as bacterial overgrowth. Therefore there may be benefits of antibiotic-based therapies for IBS. Rifaximin is a nonabsorbable antibiotic that demonstrates no clinically relevant bacterial resistance. Some studies have demonstrated the efficacy and durable improvement of IBS symptoms after treatment with rifaximin. In this review we explore the current data showing the association of small intestinal bacterial overgrowth (SIBO) and IBS as well as review the available data on the clinical use of rifaximin in the treatment of SIBO in patients with IBS. PMID:23556126

  16. Overgrowth of the indigenous gut microbiome and irritable bowel syndrome.

    PubMed

    Bye, William; Ishaq, Naveed; Bolin, Terry D; Duncombe, Vic M; Riordan, Stephen M

    2014-03-14

    Culture-independent molecular techniques have demonstrated that the majority of the gut microbiota is uncultivable. Application of these molecular techniques to more accurately identify the indigenous gut microbiome has moved with great pace over recent years, leading to a substantial increase in understanding of gut microbial communities in both health and a number of disorders, including irritable bowel syndrome (IBS). Use of culture-independent molecular techniques already employed to characterise faecal and, to a lesser extent, colonic mucosal microbial populations in IBS, without reliance on insensitive, traditional microbiological culture techniques, has the potential to more accurately determine microbial composition in the small intestine of patients with this disorder, at least that occurring proximally and within reach of sampling. Current data concerning culture-based and culture-independent analyses of the small intestinal microbiome in IBS are considered here. PMID:24627582

  17. [Irritable Bowel Syndrome; gut microbiota and probiotic therapy].

    PubMed

    Tojo González, Rafael; Suarez Gonzalez, Adolfo; Rúas Madiedo, Patricia; Mancebo Mata, Alejo; Pipa Muñiz, María; Barreiro Alonso, Eva; Roman Llorente, Francisco Javier; Moro Villar, María Carmen; Arce González, Marta María; Villegas Diaz, María Francisca; Mosquera Sierra, Eugenia; Ruiz Ruiz, Mónica

    2015-01-01

    Irritable bowel syndrome (IBS) is characterized by symptoms of abdominal pain and altered bowel habits. This common disorder is managed by varying clinical styles as no dominant therapeutic strategy has emerged. The pathophysiology of IBS remains unknown, but several lines of evidence link this disorder with the gut microbiota. Although controversy exists, gut microbiota is likely contributing to symptoms of IBS, at least in some patients, through an altered fermentation process, an impaired intestinal barrier function, a harmful modulation of enteric sensorimotor function, a promotion of low-grade inflammation without tissue damage, and a harmful modulation of the brain-gut axis. Probiotic therapy has a modest effect on IBS symptomatic relief, but the actual evidence is not strong enough to support a general recommendation of use. The best results are achieved, in children, with Lactobacillus rhamnusus GG, which moderately improves abdominal pain, while in adults the benefit appears to be greatest employing Bifidobacterium species. PMID:25659060

  18. Clinical trials in irritable bowel syndrome: a review.

    PubMed

    Ervin, Claire M; Mangel, Allen W

    2013-03-01

    Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders and it is characterized by episodes of abdominal pain and altered bowel functions. The specific bowel disturbances of diarrhea, constipation or an alternation between the two defines the IBS subtypes of diarrhea-predominant, constipation-predominant, and mixed or alternating IBS. Because of the abnormalities in bowel states associated with each IBS subtype, it is not likely that one agent would successfully treat all three subtypes. As a result, clinical trials have focused, for the most part, on one IBS subtype. Over the past 2 decades very few agents have achieved regulatory approval for the treatment of IBS. In the present article we review publications reporting on phase 2 and phase 3 studies evaluating agents to potentially be used in the treatment of patients with IBS. PMID:23130604

  19. Placebo Effect in Clinical Trial Design for Irritable Bowel Syndrome

    PubMed Central

    Shah, Eric; Pimentel, Mark

    2014-01-01

    Ongoing efforts to improve clinical trial design in irritable bowel syndrome have been hindered by high placebo response rates and ineffective outcome measures. We assessed established strategies to minimize placebo effect as well as the various approaches to placebo effect which can affect trial design. These include genetic markers such as catechol-O-methyltransferase, opioidergic and dopaminergic neurobiologic theory, pre-cebo effect centered on expectancy theory, and side effect unblinding grounded on conditioning theory. We reviewed endpoints used in the study of IBS over the past decade including adequate relief and subjective global relief, emphasizing their weaknesses in fully evaluating the IBS condition, specifically their motility effects based on functional net value and relative benefit-harm based on dropouts due to adverse events. The focus of this review is to highlight ongoing efforts to improve clinical trial design which can lead to better outcomes in a real-world setting. PMID:24840369

  20. Symbolic dynamics of jejunal motility in the irritable bowel

    NASA Astrophysics Data System (ADS)

    Wackerbauer, Renate; Schmidt, Thomas

    1999-09-01

    Different studies of the irritable bowel syndrome (IBS) by conventional analysis of jejunal motility report conflicting results. Therefore, our aim is to quantify the jejunal contraction activity by symbolic dynamics in order to discriminate between IBS and control subjects. Contraction amplitudes during fasting motility (phase II) are analyzed for 30 IBS and 30 healthy subjects. On the basis of a particular scale-independent discretization of the contraction amplitudes with respect to the median, IBS patients are characterized by increased block entropy as well as increased mean contraction amplitude. In a further more elementary level of analysis these differences can be reduced to specific contraction patterns within the time series, namely the fact that successive large contraction amplitudes are less ordered in IBS than in controls. These significant differences in jejunal motility may point to an altered control of the gut in IBS, although further studies on a representative number of patients have to be done for a validation of these findings.

  1. Is fructose malabsorption a cause of irritable bowel syndrome?

    PubMed

    DiNicolantonio, James J; Lucan, Sean C

    2015-09-01

    Irritable Bowel Syndrome (IBS) is a condition that may be marked by abdominal pain, bloating, fullness, indigestion, belching, constipation and/or diarrhea. IBS symptoms can result from malabsorption of fructose. Fructose is a monosaccharide found naturally in small quantities in fruits and some vegetables, and in much larger quantities in industrially manufactured sweets with added sugars (e.g. sucrose and high fructose corn syrup). Fructose malabsorption leads to osmotic diarrhea as well as gas and bloating due to fermentation in the colon. A low-fructose diet has been found to improve IBS symptoms in some patients. This paper discusses the prevalence of fructose malabsorption and considers fructose ingestion as a possible cause of--and fructose restriction as a possible dietary treatment for--IBS. PMID:26059250

  2. Role of environmental pollution in irritable bowel syndrome

    PubMed Central

    Marynowski, Mateusz; Likońska, Aleksandra; Zatorski, Hubert; Fichna, Jakub

    2015-01-01

    Irritable bowel syndrome (IBS), with the prevalence of 10%-20 % of the population has become an emerging problem worldwide. IBS is a functional gastrointestinal (GI) disorder characterized by abdominal pain or discomfort and altered bowel habits. The etiology of IBS contains genetic, psychological, and immunological factors, and has not been fully elucidated; of note, recent studies also point at environmental pollution and its role in the development of functional GI diseases. In this review we focus on several environmental factors, such as bacterial contamination, air pollution, radiation and even stress as potential triggers of IBS. We discuss associated disturbances in homeostasis, such as changes in intestinal microbiome and related pathophysiological mechanisms. Based on the effect of environmental factors on the GI tract, we also propose novel targets in IBS treatment. PMID:26523104

  3. New and Investigational Agents for Irritable Bowel Syndrome.

    PubMed

    Wadhwa, Akhilesh; Camilleri, Michael; Grover, Madhusudan

    2015-12-01

    Irritable bowel syndrome (IBS) affects about 15 % of the US population and results in significant morbidity and health care costs. There remains a significant unmet need for effective treatments particularly for the pain component of IBS and other functional gastrointestinal disorders (FGIDs). Progress made in our understanding of pathophysiological mechanisms such as the role of altered bile acid metabolism, neurohormonal regulation, immune dysfunction, the epithelial barrier and secretory properties of the gut has led to advancements in therapeutic armamentarium for IBS. This review discusses the new drugs for constipation and diarrhea-predominant IBS subtypes that have been tested or have been under investigation over the last 3-4 years. Overall, there is a promising pipeline of investigational drugs for the future treatment of IBS and related FGIDs. PMID:26446557

  4. Intestinal secretory mechanisms in irritable bowel syndrome-diarrhea.

    PubMed

    Camilleri, Michael

    2015-06-01

    Although diarrhea is the predominant bowel dysfunction in as many as one-third of patients with irritable bowel syndrome (IBS), it is unclear whether there is a specific disorder of intestinal fluid or electrolyte secretion in IBS. Diarrhea is generally considered a result of accelerated colonic transit in patients with IBS. Although a primary secretory diathesis has not been well-documented in patients with IBS with diarrhea (IBS-D), several mechanisms that could potentially contribute to intestinal secretion have been reported. Some of these mechanisms also influence motor and secretory dysfunctions that contribute to the pathophysiology of IBS-D. We review the evidence supporting secretion in IBS-D caused by peptides and amines produced by enteroendocrine cells or submucosal neurons, enterocyte secretory processes, and intraluminal factors (bile acids and short-chain fatty acids). Understanding these mechanisms and developing clinical methods for their identification could improve management of patients with IBS-D. PMID:25041862

  5. Low-FODMAP Diet for Treatment of Irritable Bowel Syndrome

    PubMed Central

    Magge, Suma

    2012-01-01

    Functional bowel disorders, including irritable bowel syndrome (IBS), are common disorders that have a significant impact on patients’ quality of life. These disorders present major challenges to healthcare providers, as few effective medical therapies are currently available. Recently, there has been increasing interest in dietary therapies for IBS, particularly a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). Since ingestion of FODMAPs increases the delivery of readily fermentable substrates and water to the distal small intestine and colon—which results in luminal distention and gas—the reduction of FODMAPs in a patient’s diet may improve functional gastrointestinal symptoms. This paper will review the pathophysiology of IBS and the role of FODMAPs for the treatment of this condition. PMID:24672410

  6. Thermal irritation of teeth during dental treatment procedures

    PubMed Central

    Kwon, Su-Jung; Park, Yoon-Jung; Jun, Sang-Ho; Ahn, Jin-Soo; Lee, In-Bog; Cho, Byeong-Hoon; Son, Ho-Hyun

    2013-01-01

    While it is reasonably well known that certain dental procedures increase the temperature of the tooth's surface, of greater interest is their potential damaging effect on the pulp and tooth-supporting tissues. Previous studies have investigated the responses of the pulp, periodontal ligament, and alveolar bone to thermal irritation and the temperature at which thermal damage is initiated. There are also many in vitro studies that have measured the temperature increase of the pulp and tooth-supporting tissues during restorative and endodontic procedures. This review article provides an overview of studies measuring temperature increases in tooth structures during several restorative and endodontic procedures, and proposes clinical guidelines for reducing potential thermal hazards to the pulp and supporting tissues. PMID:24010075

  7. Irritable Bowel Syndrome: A Global Challenge Among Medical Students

    PubMed Central

    Qureshi, Sarah Rauf; Abdelaal, Ahmed M; Janjua, Zaynab A; Alasmari, Hajar A; Obad, Adam S; Alamodi, Abdulhadi

    2016-01-01

    Irritable bowel syndrome (IBS) has been identified as one of the more highly prevalent and costly gastrointestinal disorders. Despite its uncertain etiology, risk factors, such as stress and academic load, are well correlated with the prevalence of the disease. Being in one of the most stressful and challenging environments, medical students are predisposed to have high rates of IBS. The socioeconomic burden of the disease on its sufferers is devastating as their quality of life is reduced, mandating additional health care precautions. The aim of this article, therefore, is to review the current literature about IBS among medical students, its prevalence, associated risk factors, and diagnostic criteria. Additionally, different solutions and management options are recommended to control the disease.  PMID:27625907

  8. Inflammation in irritable bowel syndrome: Myth or new treatment target?

    PubMed Central

    Sinagra, Emanuele; Pompei, Giancarlo; Tomasello, Giovanni; Cappello, Francesco; Morreale, Gaetano Cristian; Amvrosiadis, Georgios; Rossi, Francesca; Lo Monte, Attilio Ignazio; Rizzo, Aroldo Gabriele; Raimondo, Dario

    2016-01-01

    Low-grade intestinal inflammation plays a key role in the pathophysiology of irritable bowel syndrome (IBS), and this role is likely to be multifactorial. The aim of this review was to summarize the evidence on the spectrum of mucosal inflammation in IBS, highlighting the relationship of this inflammation to the pathophysiology of IBS and its connection to clinical practice. We carried out a bibliographic search in Medline and the Cochrane Library for the period of January 1966 to December 2014, focusing on publications describing an interaction between inflammation and IBS. Several evidences demonstrate microscopic and molecular abnormalities in IBS patients. Understanding the mechanisms underlying low-grade inflammation in IBS may help to design clinical trials to test the efficacy and safety of drugs that target this pathophysiologic mechanism. PMID:26900287

  9. Chronic Rhinosinusitis and Irritable Bowel Syndrome: A Case Report

    PubMed Central

    Kogan, Mikhail; Castillo, Carlos Cuellar; Barber, Melissa S.

    2016-01-01

    Introduction Chronic rhinosinusitis (CRS) and irritable bowel syndrome (IBS) can be comorbidities that are difficult to treat. In this patient, an evidence-informed treatment pathway guided by laboratory biomarkers was used to address both conditions. Case Presentation A 69-y-old female patient presented with a 50-y history of sinusitis that was worse in the winter, postnasal drip, frequent sore throats, gastrointestinal complaints, headaches, and yeast infections. Two sinus surgeries (in years 2000 and 2002) and multiple courses of antibiotics had not resolved her sinus symptoms. In addition to CRS and IBS, this patient was noted to have intestinal overgrowth of Candida albicans, multiple food sensitivities, and leaky gut syndrome. Conclusion Antifungal medication and dietary changes in the course of 8 mo resulted in the resolution of her CRS and IBS. PMID:27547167

  10. Recent advances in the diagnosis of irritable bowel syndrome.

    PubMed

    El-Salhy, Magdy

    2015-01-01

    The symptom-based diagnosis of irritable bowel syndrome (IBS) has not been established in everyday clinical practice, and the diagnosis of this disorder remains one of exclusion. It has been demonstrated that the densities of duodenal chromogranin A, rectal peptide YY and somatostatin cells are good biomarkers for the diagnosis of sporadic IBS, and low-grade mucosal inflammation is a promising biomarker for the diagnosis of postinfectious IBS. Genetic markers are not useful as biomarkers for IBS since the potential risk genes have yet to be validated, and the intestinal microbiota cannot be used because of the lack of an association between a specific bacterial species and IBS. Furthermore, gastrointestinal dysmotility and visceral hypersensitivity tests produce results that are too nonconsistent and noncharacteristic to be used in the diagnosis of IBS. A combination of symptom-based assessment, exclusion of overlapping gastrointestinal diseases and positive biomarkers appears to be the best way to diagnose IBS. PMID:26162959

  11. Current and Novel Therapeutic Options for Irritable Bowel Syndrome Management

    PubMed Central

    Camilleri, Michael; Andresen, Viola

    2009-01-01

    Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder affecting up to 3-15% of the general population in western countries. It is characterized by unexplained abdominal pain, discomfort, and bloating in association with altered bowel habits. The pathophysiology of IBS is multifactorial involving disturbances of the brain-gut-axis. The pathophysiology provides the rationale for pharmacotherapy: abnormal gastrointestinal motor functions, visceral hypersensitivity, psychosocial factors, autonomic dysfunction, and mucosal immune activation. Understanding the mechanisms, and their mediators or modulators including neurotransmitters and receptors have led to several therapeutic approaches including agents acting on the serotonin receptor or serotonin transporter system, antidepressants, novel selective anticholinergics, α-adrenergic agonists, opioid agents, cholecystokinin-antagonists, neurokinin-antagonists, somatostatin receptor agonists, corticotropin releasing factor antagonists, chloride-channel activators, guanylate-cyclase-c agonists, melatonin, atypical benzodiazepines, antibiotics, immune modulators and probiotics. The mechanisms and current evidence regarding efficacy of these agents are reviewed. PMID:19665953

  12. Cluster belly: a variant of irritable bowel syndrome.

    PubMed

    Robbins, Matthew S

    2014-01-01

    Cluster headache (CH) and irritable bowel syndrome (IBS) are pain disorders that possess relationships with circadian rhythms. However, they have not been compared to assess similarities that could yield pathophysiologic insights. A young male adult with periodic episodes of abdominal pain highly reminiscent of CH is described. Since childhood, he experienced severe attacks featuring excruciating, abdominal pain accompanied by prominent restlessness, lasting 30-120 minutes, occurring in the evening and in discrete 2- to 8-week periods, interspersed with remissions where typical triggers did not lead to attacks. Although all of the patient's symptoms fell within the spectrum of IBS, the semiology was highly evocative of CH, based on the attack duration, restlessness, periodicity, and selective vulnerability to particular triggers only during attack periods. A subset of patients thought to have IBS may feature similar attack profiles and could suggest the importance of the hypothalamus in its pathophysiology, akin to CH. PMID:25039367

  13. Mind/Body Psychological Treatments for Irritable Bowel Syndrome

    PubMed Central

    Fresé, Michael P.; Rapgay, Lobsang

    2008-01-01

    Currently, the goal of treatment for those with irritable bowel syndrome (IBS) is to improve the quality of life through a reduction in symptoms. While the majority of treatment approaches involve the use of traditional medicine, more and more patients seek out a non-drug approach to managing their symptoms. Current forms of non-drug psychologic or mind/body treatment for IBS include hypnotherapy, cognitive behavioral therapy and brief psychodynamic psychotherapy, all of which have been proven efficacious in clinical trials. We propose that incorporating the constructs of mindfulness and acceptance into a mind/body psychologic treatment of IBS may be of added benefit due to the focus on changing awareness and acceptance of one's own state which is a strong component of traditional and Eastern healing philosophies. PMID:18317547

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

    PubMed

    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. PMID:26872433

  15. Irritable Bowel Syndrome: A Global Challenge Among Medical Students.

    PubMed

    Qureshi, Sarah Rauf; Abdelaal, Ahmed M; Janjua, Zaynab A; Alasmari, Hajar A; Obad, Adam S; Alamodi, Abdulhadi; Shareef, Mohammad Abrar

    2016-01-01

    Irritable bowel syndrome (IBS) has been identified as one of the more highly prevalent and costly gastrointestinal disorders. Despite its uncertain etiology, risk factors, such as stress and academic load, are well correlated with the prevalence of the disease. Being in one of the most stressful and challenging environments, medical students are predisposed to have high rates of IBS. The socioeconomic burden of the disease on its sufferers is devastating as their quality of life is reduced, mandating additional health care precautions. The aim of this article, therefore, is to review the current literature about IBS among medical students, its prevalence, associated risk factors, and diagnostic criteria. Additionally, different solutions and management options are recommended to control the disease. PMID:27625907

  16. Irritable bowel syndrome: Relations with functional, mental, and somatoform disorders

    PubMed Central

    Hausteiner-Wiehle, Constanze; Henningsen, Peter

    2014-01-01

    This review describes the conceptual and clinical relations between irritable bowel syndrome (IBS), other functional, somatoform, and mental disorders, and points to appropriate future conceptualizations. IBS is considered to be a functional somatic syndrome (FSS) with a considerable symptom overlap with other FSSs like chronic fatigue syndrome or fibromyalgia syndrome. IBS patients show an increased prevalence of psychiatric symptoms and disorders, especially depression and anxiety. IBS is largely congruent with the concepts of somatoform and somatic symptom disorders. Roughly 50% of IBS patients complain of gastrointestinal symptoms only and have no psychiatric comorbidity. IBS concepts, treatment approaches, as well as health care structures should acknowledge its variability and multidimensionality by: (1) awareness of additional extraintestinal and psychobehavioral symptoms in patients with IBS; (2) general and collaborative care rather than specialist and separated care; and (3) implementation of “interface disorders” to abandon the dualistic classification of purely organic or purely mental disorders. PMID:24876725

  17. Irritable bowel syndrome: relations with functional, mental, and somatoform disorders.

    PubMed

    Hausteiner-Wiehle, Constanze; Henningsen, Peter

    2014-05-28

    This review describes the conceptual and clinical relations between irritable bowel syndrome (IBS), other functional, somatoform, and mental disorders, and points to appropriate future conceptualizations. IBS is considered to be a functional somatic syndrome (FSS) with a considerable symptom overlap with other FSSs like chronic fatigue syndrome or fibromyalgia syndrome. IBS patients show an increased prevalence of psychiatric symptoms and disorders, especially depression and anxiety. IBS is largely congruent with the concepts of somatoform and somatic symptom disorders. Roughly 50% of IBS patients complain of gastrointestinal symptoms only and have no psychiatric comorbidity. IBS concepts, treatment approaches, as well as health care structures should acknowledge its variability and multidimensionality by: (1) awareness of additional extraintestinal and psychobehavioral symptoms in patients with IBS; (2) general and collaborative care rather than specialist and separated care; and (3) implementation of "interface disorders" to abandon the dualistic classification of purely organic or purely mental disorders. PMID:24876725

  18. Irritation fibroma removal: a comparison of two laser wavelengths.

    PubMed

    Walinski, Christopher J

    2004-01-01

    Laser wavelengths are available that offer dentists treatment options for both hard and soft oral tissues. This article discusses the benefits of removing hypertrophic soft tissue by using an all-tissue laser. A clinical case is presented involving the use of both an 810 nm diode laser and a 2,780 nm Er,Cr:YSGG laser to remove two irritation fibromas, both located on the left cheek of the same patient. This unique perspective was ideal for comparing the healing of each wound. The Er,Cr:YSGG appeared to have a less traumatic effect on target tissue and offered improved postoperative healing, faster recovery time, and less trauma than traditional surgical modalities. PMID:15206255

  19. Quality of life measures in irritable bowel syndrome.

    PubMed

    Wong, Reuben K M; Drossman, Douglas A

    2010-06-01

    Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder with significant morbidity, resulting from the interaction of physiologic, psychological, social, cultural and behavioral factors. In view of this complex interaction, and in the absence of a measurable biological index of disease, health-related quality of life (HRQoL) has emerged as an ideal measure for use in clinical trials and outcome studies. This article discusses the relevance of HRQoL measurement in IBS and its definition. It then explores the research methodology in HRQoL and describes how global measures and generic HRQoL instruments have been used in IBS. Finally, the IBS-specific HRQoL measures are described in detail, with an emphasis on their development, content and validation. PMID:20528115

  20. Dicationic Alkylammonium Bromide Gemini Surfactants. Membrane Perturbation and Skin Irritation

    PubMed Central

    Almeida, João A. S.; Faneca, Henrique; Carvalho, Rui A.; Marques, Eduardo F.; Pais, Alberto A. C. C.

    2011-01-01

    Dicationic alkylammonium bromide gemini surfactants represent a class of amphiphiles potentially effective as skin permeation enhancers. However, only a limited number of studies has been dedicated to the evaluation of the respective cytotoxicity, and none directed to skin irritation endpoints. Supported on a cell viability study, the cytotoxicity of gemini surfactants of variable tail and spacer length was assessed. For this purpose, keratinocyte cells from human skin (NCTC 2544 cell line), frequently used as a model for skin irritation, were employed. The impact of the different gemini surfactants on the permeability and morphology of model vesicles was additionally investigated by measuring the leakage of calcein fluorescent dye and analyzing the NMR spectra of 31P, respectively. Detail on the interaction of gemini molecules with model membranes was also provided by a systematic differential scanning calorimetry (DSC) and molecular dynamics (MD) simulation. An irreversible impact on the viability of the NCTC 2544 cell line was observed for gemini concentrations higher than 25 mM, while no cytotoxicity was found for any of the surfactants in a concentration range up to 10 mM. A higher cytotoxicity was also found for gemini surfactants presenting longer spacer and shorter tails. The same trend was obtained in the calorimetric and permeability studies, with the gemini of longest spacer promoting the highest degree of membrane destabilization. Additional structural and dynamical characterization of the various systems, obtained by 31P NMR and MD, provide some insight on the relationship between the architecture of gemini surfactants and the respective perturbation mechanism. PMID:22102870

  1. Evaluation of TOPKAT, Toxtree, and Derek Nexus in Silico Models for Ocular Irritation and Development of a Knowledge-Based Framework To Improve the Prediction of Severe Irritation.

    PubMed

    Bhhatarai, Barun; Wilson, Daniel M; Parks, Amanda K; Carney, Edward W; Spencer, Pamela J

    2016-05-16

    Assessment of ocular irritation is an essential component of any risk assessment. A number of (Q)SARs and expert systems have been developed and are described in the literature. Here, we focus on three in silico models (TOPKAT, BfR rulebase implemented in Toxtree, and Derek Nexus) and evaluate their performance using 1644 in-house and 123 European Centre for Toxicology and Ecotoxicology of Chemicals (ECETOC) compounds with existing in vivo ocular irritation classification data. Overall, the in silico models performed poorly. The best consensus predictions of severe ocular irritants were 52 and 65% for the in-house and ECETOC compounds, respectively. The prediction performance was improved by designing a knowledge-based chemical profiling framework that incorporated physicochemical properties and electrophilic reactivity mechanisms. The utility of the framework was assessed by applying it to the same test sets and three additional publicly available in vitro irritation data sets. The prediction of severe ocular irritants was improved to 73-77% if compounds were filtered on the basis of AlogP_MR (hydrophobicity with molar refractivity). The predictivity increased to 74-80% for compounds capable of preferentially undergoing hard electrophilic reactions, such as Schiff base formation and acylation. This research highlights the need for reliable ocular irritation models to be developed that take into account mechanisms of action and individual structural classes. It also demonstrates the value of profiling compounds with respect to their chemical reactivity and physicochemical properties that, in combination with existing models, results in better predictions for severe irritants. PMID:27018716

  2. Inhibition of irritation and contact hypersensitivity by phenoxyacetic acid methyl ester in mice.

    PubMed

    Wille, J J; Kydonieus, A; Kalish, R S

    2000-01-01

    New anti-irritant treatments are required to prevent irritation and sensitization reactions to consumer medicines and dermatological drugs. We report here that phenoxyacetic acid methyl ester (PAME) is an effective agent to prevent and treat irritant and allergic contact dermatitis. Balb/c mice skin-treated with 1% PAME do not lose weight relative to vehicle-treated mice, nor is it irritating to mouse skin. Topical PAME prevents skin irritation to a wide variety of irritants including: arachidonic acid, capsaicin, sodium lauryl sulfate (SLS), disodium laureth sulfosuccinate and tetradecanoylphorbol-13-acetate. Histological studies showed that 1% PAME greatly diminished dermal neutrophilic infiltration and dermal capillary vessel dilation, and prevented epidermal hyperproliferation and hyperkeratosis that accompanies detergent (SLS)-induced skin irritation. Topical PAME inhibited ear swelling following ear challenge during the elicitation phase of contact hypersensitivity in mice sensitized with 1-chloro-2, 4-dinitrochlorobenzene (DNCB), oxazolone and the hair coloring dye rho-phenylenediamine (PPD). Finally, topical administration of 1% PAME prior to PPD or DNCB sensitization prevented the induction phase of contact hypersensitivity. These results indicate that PAME represents a potential new category of potent topical anti-inflammatory agents. PMID:10754454

  3. The role of dermal irritation in the skin tumor promoting activity of petroleum middle distillates.

    PubMed

    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. PMID:10367341

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

    PubMed Central

    Contri, Renata V; Frank, Luiza A; Kaiser, Moacir; Pohlmann, Adriana R; Guterres, Silvia S

    2014-01-01

    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. PMID:24611011

  5. Constructing Human Skin Equivalents on Porcine Acellular Peritoneum Extracellular Matrix for In Vitro Irritation Testing.

    PubMed

    Tsai, Pei-Chin; Zhang, Zheng; Florek, Charles; Michniak-Kohn, Bozena B

    2016-01-01

    The irritancy of topical products has to be investigated to ensure the safety and compliance. Although several reconstructed human epidermal models have been adopted by the Organization for Economic Cooperation and Development (OECD) to replace in vivo animal irritation testing, these models are based on a single cell type and lack dermal components, which may be insufficient to reflect all of the components of irritation. In our study, we investigated the use of acellular porcine peritoneum extracellular matrix as a substrate to construct full-thickness human skin equivalents (HSEs) for use as irritation screening tool. The acellular peritoneum matrix (APM) exhibited excellent skin cell attachment (>80%) and proliferation for human dermal fibroblasts (HDF) and immortalized human keratinocytes (HaCaT). APM-HSEs based on coculture of HDF and HaCaT were prepared. Increased HDF seeding density up to 5 × 10(4)/cm(2) resulted in APM-HSEs with a thicker and more organized epidermis. The epidermis of APM-HSEs expressed keratin 15, a keratinocyte proliferation marker, and involucrin, a differentiation marker, respectively. To assess the use of APM-HSEs for irritation testing, six proficiency chemicals, including three nonirritants (phosphate-buffered saline, polyethylene glycol 400, and isopropanol) and three irritants (1-bromohexane, heptanol, and sodium dodecyl sulfate) were applied. The APM-HSEs were able to discriminate nonirritants from irritants based on the viability. Levels of cytokines (interleukin [IL]-1α, IL-1ra, IL-6, IL-8, and granulocyte macrophage colony-stimulating factor [GM-CSF]) in these treatment groups further assisted the irritancy ranking. In conclusion, we have developed partially differentiated full-thickness APM-HSEs based on acellular porcine peritoneum matrix, and these APM-HSEs demonstrated utility as an in vitro irritation screening tool. PMID:26415037

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

    PubMed

    Ha, Michael A; Smith, Gregory J; Cichocki, Joseph A; Fan, Lu; Liu, Yi-Shiuan; Caceres, Ana I; Jordt, Sven Eric; Morris, John B

    2015-01-01

    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 promote smoking

  7. Menthol Attenuates Respiratory Irritation and Elevates Blood Cotinine in Cigarette Smoke Exposed Mice

    PubMed Central

    Ha, Michael A.; Smith, Gregory J.; Cichocki, Joseph A.; Fan, Lu; Liu, Yi-Shiuan; Caceres, Ana I.; Jordt, Sven Eric; Morris, John B.

    2015-01-01

    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 promote smoking

  8. Rat epidermal keratinocyte organotypic culture (ROC) as a model for chemically induced skin irritation testing

    SciTech Connect

    Pappinen, Sari . E-mail: sari.pappinen@uku.fi; Pasonen-Seppaenen, Sanna; Suhonen, Marjukka; Tammi, Raija; Urtti, Arto

    2005-11-01

    The potential of rat epidermal keratinocyte (REK) organotypic culture (ROC) with proper stratum corneum barrier as a model for screening skin irritants was evaluated. The test chemicals were selected from ECETOC database (1995) and the observed in vitro irritation potential was compared to ECETOC in vivo primary irritation index (PII), to EU risk phrases, and to the harmonized OECD criteria. Chemicals were applied onto the stratum corneum surface of ROC for 30 min and samples were taken from the underlying medium at 4 and 8 h after exposure. Cell membrane integrity (determined by LDH assay) and pro-inflammatory effect (determined by IL-1{alpha} release) were verified at both time points and correlated to PII values. The best correlation (R {sup 2} = 0.831) was seen with LDH leakage test. Based on obtained data, chemicals were classified according to criteria defined by EU and OECD. From 12 chemicals, only two were incorrectly classified according to OECD criteria when using LDH leakage and IL-1{alpha} release as irritation markers. At the end of experiment, chemical-treated ROC cultures were fixed and histological changes were assessed. Typical signs for irritation were lightly stained cytoplasm, condensed nuclei, cellular vacuolization, eosinophilic cytoplasms, and blebbing. These irritation effects of chemicals were graded visually into four classes (A-D). The extent of morphological perturbations of the cultures mostly correlated with PII. The present results indicate the validity of the ROC model in predicting skin irritation potential of chemicals and show that the use of set of irritation markers with different mechanistic responses gives more information on irritation than if only one marker was used.

  9. Occupational airways diseases from chronic low-level exposures to irritants.

    PubMed

    Balmes, John R

    2002-12-01

    Short-term, high-level exposures to dusts, gases, mists, fumes, and smoke that are irritating to the respiratory tract are capable of inducing asthma, the so-called reactive airways dysfunction syndrome. Such exposures, however, do not occur frequently; chronic or recurrent exposures to lower levels of irritants are much more common. This article reviews the evidence that supports the concept that low-level exposures to respiratory tract irritants can contribute to the development of chronic obstructive pulmonary disease and asthma. PMID:12512162

  10. Formation of strong airway irritants in mixtures of isoprene/ozone and isoprene/ozone/nitrogen dioxide.

    PubMed Central

    Wilkins, C K; Clausen, P A; Wolkoff, P; Larsen, S T; Hammer, M; Larsen, K; Hansen, V; Nielsen, G D

    2001-01-01

    We evaluated the airway irritation of isoprene, isoprene/ozone, and isoprene/ozone/nitrogen dioxide mixtures using a mouse bioassay, from which we calculated sensory irritation, bronchial constriction, and pulmonary irritation. We observed significant sensory irritation (approximately 50% reduction of mean respiratory rate) by dynamically exposing the mice, over 30 min, to mixtures of isoprene and O3 or isoprene, O3, and NO2. The starting concentrations were approximately 4 ppm O3 and 500 ppm isoprene (+ approximately 4 ppm NO2. The reaction mixtures after approximately 30 sec contained < 0.2 ppm O3. Addition of the effects of the residual reactants and the identified stable irritant products (formaldehyde, formic acid, acetic acid, methacrolein, and methylvinyl ketone) could explain only partially the observed sensory irritation. This suggests that one or more strong airway irritants were formed. It is thus possible that oxidation reactions of common unsaturated compounds may be relevant for indoor air quality. PMID:11673123

  11. Respiratory and eye irritation from boron oxide and boric acid dusts

    SciTech Connect

    Garabrant, D.H.; Bernstein, L.; Peters, J.M.; Smith, T.J.

    1984-08-01

    Boron oxide has been shown in animals to irritate the respiratory mucosa and conjuctiva. The present study was undertaken to determine whether exposures to boron oxide and its hydration product, boric acid, cau

  12. Irritable Bowel Syndrome and Complementary Health Practices: What the Science Says

    MedlinePlus

    ... Health Approaches for Irritable Bowel Syndrome: What the Science Says Share: July 2015 © Tom Le Goff/Digital ... products and practices in the context of rigorous science, training complementary health researchers, and disseminating authoritative information ...

  13. Irritant contact dermatitis complicated by deep-seated staphylococcal infection caused by a hair relaxer.

    PubMed

    Kaur, Birinder J; Singh, Harmeet; Lin-Greenberg, Alan

    2002-02-01

    Chemical hair relaxers are used by many women to straighten their hair. We describe a case of a deep soft tissue staphylococcal abscess that complicated an irritant contact dermatitis from a hair relaxer treatment. PMID:11853045

  14. Irritant contact dermatitis complicated by deep-seated staphylococcal infection caused by a hair relaxer.

    PubMed Central

    Kaur, Birinder J.; Singh, Harmeet; Lin-Greenberg, Alan

    2002-01-01

    Chemical hair relaxers are used by many women to straighten their hair. We describe a case of a deep soft tissue staphylococcal abscess that complicated an irritant contact dermatitis from a hair relaxer treatment. PMID:11853045

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

    PubMed Central

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

    2016-01-01

    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. PMID:27134650

  16. Airborne irritant contact dermatitis and conjunctivitis after occupational exposure to chlorothalonil in textiles.

    PubMed

    Lensen, Gerda; Jungbauer, Frank; Gonçalo, Margarida; Coenraads, Pieter Jan

    2007-09-01

    Chlorothalonil (tetrachloro-1,3-benzenedicarbonitrile, CAS 1897-45-6) is a pesticide that has been on the market for many years. It is used as a fungicide in agriculture, horticulture, and floriculture; as a wood preservative; and in paint. We report an epidemic of airborne irritant contact dermatitis, conjunctivitis, and upper airway complaints among seamstresses in a Portuguese trailer tent factory, which we attribute to chlorothalonil. All exposed workers had work-related skin symptoms. After patch testing, we showed that none of these were of allergic origin. Instead of allergic reactions, we noticed a delayed type of irritation after 72 hr to chlorothalonil and to the textile extracts containing high concentrations of chlorothalonil. Although allergic and irritant contact dermatitis from chlorothalonil has been described before, this is, as far as we know, the first time that a delayed type of dermatitis, conjunctivitis, and upper airway irritation after exposure to chlorothalonil in tent-cloth is described. PMID:17680869

  17. Workplace irritant exposures: do they produce true occupational asthma?

    PubMed

    Banks, D E

    2001-04-01

    The recognition that irritant exposures can cause asthma is not new. Many investigators turn towards the gassings of soldiers in World War I as the first examples of this, while Brooks, in 1985, reported this in detail in workers and called it 'Reactive Airways Dysfunction Syndrome (RADS)'. There is considerable overlap with RADS and occupational asthma as both share respiratory symptoms which can be described as 'asthmatic', yet RADS is the result of an acute excessive exposure, while occupational asthma occurs due to a series of sensitizing exposures. Yet, a clear understanding of RADS has been limited by the lack of epidemiologic studies; rather the disease has been described by case series. This report contrasts RADS and occupational asthma and finds that although there may be some difference in lung pathology, reports for the past years since Brooks' initial reports have shown that the line separating occupational asthma and RADS has become increasingly blurred, rather than increasingly distinct, with considerable overlap in the clinical symptoms with the perspective that these described entities are a part of a continuum. Perhaps the development of animal models for RADS may hasten further understanding. PMID:11964685

  18. Personality traits and emotional patterns in irritable bowel syndrome

    PubMed Central

    Muscatello, Maria Rosaria A; Bruno, Antonio; Mento, Carmela; Pandolfo, Gianluca; Zoccali, Rocco A

    2016-01-01

    The review focuses on those personality traits (neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness), constructs (alexithymia and distressed - Type D personality) and emotional patterns (negative and positive) that are of particular concern in health psychology, with the aim to highlight their potential role on the pathogenesis, onset, symptom clusters, clinical course, and outcome of irritable bowel syndrome (IBS). Personality traits and emotional patterns play key roles in affecting autonomic, immune, inflammatory, and endocrine functions, thus contributing not only to IBS clinical expression and symptomatic burden, but also to disease physiopathology. In this sense, psychological treatments should address those personality traits and emotional features that are constitutive of, and integral to IBS. The biopsychosocial model of illness applied to IBS acknowledges the interaction between biological, psychological, environmental, and social factors in relation to pain and functional disability. A holistic approach to IBS should take into account the heterogeneous nature of the disorder, and differentiate treatments for different types of IBS, also considering the marked individual differences in prevalent personality traits and emotional patterns. Beyond medications, and lifestyle/dietary interventions, psychological and educational treatments may provide the optimal chance of addressing clinical symptoms, comorbid conditions, and quality of life in IBS patients. PMID:27605876

  19. Irritable bowel syndrome and chronic constipation: Fact and fiction

    PubMed Central

    Bellini, Massimo; Gambaccini, Dario; Usai-Satta, Paolo; De Bortoli, Nicola; Bertani, Lorenzo; Marchi, Santino; Stasi, Cristina

    2015-01-01

    Irritable bowel syndrome (IBS) and functional constipation (FC) are the most common functional gastrointestinal disorders. According to the Rome III Criteria these two disorders should be theoretically separated mainly by the presence of abdominal pain or discomfort relieved by defecation (typical of IBS) and they should be mutually exclusive. However, many gastroenterologists have serious doubts as regards a clear separation. Both IBS-C and FC, often associated with many other functional digestive and non digestive disorders, are responsible for a low quality of life. The impact of the media on patients’ perception of these topics is sometimes disruptive, often suggesting a distorted view of pathophysiology, diagnosis and therapy. These messages frequently overlap with previous subjective opinions and are further processed on the basis of the different culture and the previous experience of the constipated patients, often producing odd, useless or even dangerous behaviors. The aim of this review was to analyze the most common patients’ beliefs about IBS-C and CC, helping physicians to understand where they should focus their attention when communicating with patients, detecting false opinions and misconceptions and correcting them on the basis of scientific evidence. PMID:26523103

  20. Treatment of Dientamoeba fragilis in Patients with Irritable Bowel Syndrome

    PubMed Central

    Engsbro, Anne Line; Stensvold, C. Rune; Nielsen, Henrik V.; Bytzer, Peter

    2012-01-01

    The role of Dientamoeba fragilis in irritable bowel syndrome (IBS) is incompletely known. We aimed to investigate whether eradication of D. fragilis alleviates symptoms in IBS. Twenty-five D. fragilis-positive IBS patients were treated with Metronidazole (MZ) or Tetracycline. The patients were mostly female (89%), and mean age (SD) was 35.1 (8.2) years. Microbiological response, evaluated 2 weeks post-treatment, was observed in 15 of 25 patients (60%), all by MZ. Clinical response, defined as adequate relief of symptoms, was observed in 7 of 22 patients (32%), all by MZ. In a logistic regression analysis, we found no significant association between clinical and microbiological response. This case study did not support our hypothesis of a simple association between D. fragilis and IBS. Some D. fragilis-infections were insufficiently treated by MZ. Further studies into the prevalence and effect of eradication of D. fragilis in IBS and into efficient treatments of D. fragilis are warranted. PMID:23091195

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

    PubMed

    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. PMID:24627584

  2. Irritable bowel syndrome: a microbiome-gut-brain axis disorder?

    PubMed

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

    2014-10-21

    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

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

    PubMed

    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. PMID:25083061

  4. Treatment of irritable bowel syndrome: beyond fiber and antispasmodic agents

    PubMed Central

    Sainsbury, Anita; Ford, Alexander C.

    2011-01-01

    Irritable bowel syndrome (IBS) is a chronic functional disorder of the gastrointestinal tract of unknown etiology. The diagnosis of IBS is made clinically, using symptom-based criteria such as the Manning or Rome criteria. Medical therapy for this condition has traditionally been directed towards symptom relief, using fiber or antispasmodic agents. In recent years, emerging data have confirmed the efficacy of antidepressants, psychological therapies, 5-HT3 antagonists, 5-HT4 agonists, and probiotics in the short-term treatment of IBS, although whether these therapies influence the long-term course of the disease is unknown. Increasing knowledge regarding the pathophysiological mechanisms underlying IBS has resulted in a number of novel molecular treatments, which show promise. These include therapies targeting gastrointestinal mucosal chloride channels and guanylate cyclase-C receptors, as well as highly selective agents influencing serotonergic transmission that, at the time of writing, do not appear to have any severe deleterious effects. In this article we provide a summary of current and emerging therapies in this field. PMID:21694813

  5. Recent advances in pharmacological treatment of irritable bowel syndrome

    PubMed Central

    Lazaraki, Georgia; Chatzimavroudis, Grigoris; Katsinelos, Panagiotis

    2014-01-01

    Irritable bowel syndrome (IBS) is a highly prevalent functional disorder that reduces patients’ quality of life. It is a chronic disorder characterized by abdominal pain or discomfort associated with disordered defecation in the absence of identifiable structural or biochemical abnormalities. IBS imposes a significant economic burden to the healthcare system. Alteration in neurohumoral mechanisms and psychological factors, bacterial overgrowth, genetic factors, gut motility, visceral hypersensitivity, and immune system factors are currently believed to influence the pathogenesis of IBS. It is possible that there is an interaction of one or more of these etiologic factors leading to heterogeneous symptoms of IBS. IBS treatment is predicated upon the patient’s most bothersome symptoms. Despite the wide range of medications and the high prevalence of the disease, to date no completely effective remedy is available. This article reviews the literature from January 2008 to July 2013 on the subject of IBS peripherally acting pharmacological treatment. Drugs are categorized according to their administration for IBS-C, IBS-D or abdominal pain predominant IBS. PMID:25083060

  6. Irritable bowel syndrome and chronic constipation: Fact and fiction.

    PubMed

    Bellini, Massimo; Gambaccini, Dario; Usai-Satta, Paolo; De Bortoli, Nicola; Bertani, Lorenzo; Marchi, Santino; Stasi, Cristina

    2015-10-28

    Irritable bowel syndrome (IBS) and functional constipation (FC) are the most common functional gastrointestinal disorders. According to the Rome III Criteria these two disorders should be theoretically separated mainly by the presence of abdominal pain or discomfort relieved by defecation (typical of IBS) and they should be mutually exclusive. However, many gastroenterologists have serious doubts as regards a clear separation. Both IBS-C and FC, often associated with many other functional digestive and non digestive disorders, are responsible for a low quality of life. The impact of the media on patients' perception of these topics is sometimes disruptive, often suggesting a distorted view of pathophysiology, diagnosis and therapy. These messages frequently overlap with previous subjective opinions and are further processed on the basis of the different culture and the previous experience of the constipated patients, often producing odd, useless or even dangerous behaviors. The aim of this review was to analyze the most common patients' beliefs about IBS-C and CC, helping physicians to understand where they should focus their attention when communicating with patients, detecting false opinions and misconceptions and correcting them on the basis of scientific evidence. PMID:26523103

  7. New and Emerging Treatment Options for Irritable Bowel Syndrome.

    PubMed

    Lacy, Brian E; Chey, William D; Lembo, Anthony J

    2015-04-01

    Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with abdominal pain, diarrhea, constipation, or a mix of symptoms. The pathophysiology of IBS is not completely understood but appears to involve genetics, the gut microbiome, immune activation, altered intestinal permeability, and brain-gut interactions. There is no gold standard for diagnosis. Several sets of symptom-based guidelines exist. Treatment strategies for IBS may include both nonpharmacologic and pharmacologic approaches. Lifestyle modifications that aim to improve exercise, sleep, diet, and stress may be warranted. Recent data suggest that a gluten-free diet and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) may benefit some patients. For patients with diarrhea-predominant IBS, treatment options include the synthetic peripheral μ-opioid receptor agonist loperamide, antispasmodic agents, antidepressants, serotonin 5-HT3 antagonists, and the gut-specific antibiotic rifaximin. Ongoing research is evaluating the use of probiotics. For patients with constipation-predominant IBS, therapeutic strategies may include dietary fiber, laxatives, and the prosecretory agents lubiprostone and linaclotide. Research is continuing to optimize the use of available agents and evaluating new approaches to further improve the care of patients with IBS. PMID:26491416

  8. Optimal management of constipation associated with irritable bowel syndrome.

    PubMed

    Furnari, Manuele; de Bortoli, Nicola; Martinucci, Irene; Bodini, Giorgia; Revelli, Matteo; Marabotto, Elisa; Moscatelli, Alessandro; Del Nero, Lorenzo; Savarino, Edoardo; Giannini, Edoardo G; Savarino, Vincenzo

    2015-01-01

    Irritable bowel syndrome (IBS) is a common chronic functional disorder of the gastrointestinal tract, meanly characterized by recurrent abdominal pain or discomfort and altered bowel habit. It is a complex disorder involving biological, environmental, and psychosocial factors. The diagnosis is achieved according to the Rome III criteria provided that organic causes have been excluded. Although IBS does not constitute a life-threatening condition, it has a remarkable prevalence and profoundly reduces the quality of life with burdening socioeconomic costs. One of the principal concerns about IBS is the lack of effective therapeutic options. Up to 40% of patients are not satisfied with any available medications, especially those suffering from chronic constipation. A correct management of IBS with constipation should evolve through a global approach focused on the patient, starting with careful history taking in order to assess the presence of organic diseases that might trigger the disorder. Therefore, the second step is to examine lifestyle, dietary habits, and psychological status. On these bases, a step-up management of disease is recommended: from fiber and bulking agents, to osmotic laxative drugs, to new molecules like lubiprostone and linaclotide. Although new promising tools for relief of bowel-movement-related symptoms are being discovered, a dedicated doctor-patient relationship still seems to be the key for success. PMID:26028974

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

    PubMed Central

    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

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

    PubMed Central

    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

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

    PubMed Central

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

    2016-01-01

    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. PMID:26900286

  12. Guidelines on the irritable bowel syndrome: mechanisms and practical management

    PubMed Central

    Spiller, R; Aziz, Q; Creed, F; Emmanuel, A; Houghton, L; Hungin, P; Jones, R; Kumar, D; Rubin, G; Trudgill, N; Whorwell, P

    2007-01-01

    Background IBS affects 5–11% of the population of most countries. Prevalence peaks in the third and fourth decades, with a female predominance. Aim To provide a guide for the assessment and management of adult patients with irritable bowel syndrome. Methods Members of the Clinical Services Committee of The British Society of Gastroenterology were allocated particular areas to produce review documents. Literature searching included systematic searches using electronic databases such as Pubmed, EMBASE, MEDLINE, Web of Science, and Cochrane databases and extensive personal reference databases. Results Patients can usefully be classified by predominant bowel habit. Few investigations are needed except when diarrhoea is a prominent feature. Alarm features may warrant further investigation. Adverse psychological features and somatisation are often present. Ascertaining the patients' concerns and explaining symptoms in simple terms improves outcome. IBS is a heterogeneous condition with a range of treatments, each of which benefits a small proportion of patients. Treatment of associated anxiety and depression often improves bowel and other symptoms. Randomised placebo controlled trials show benefit as follows: cognitive behavioural therapy and psychodynamic interpersonal therapy improve coping; hypnotherapy benefits global symptoms in otherwise refractory patients; antispasmodics and tricyclic antidepressants improve pain; ispaghula improves pain and bowel habit; 5‐HT3 antagonists improve global symptoms, diarrhoea, and pain but may rarely cause unexplained colitis; 5‐HT4 agonists improve global symptoms, constipation, and bloating; selective serotonin reuptake inhibitors improve global symptoms. Conclusions Better ways of identifying which patients will respond to specific treatments are urgently needed. PMID:17488783

  13. Irritable bowel syndrome: Physicians' awareness and patients' experience

    PubMed Central

    Olafsdottir, Linda Bjork; Gudjonsson, Hallgrímur; Jonsdottir, Heidur Hrund; Jonsson, Jon Steinar; Bjornsson, Einar; Thjodleifsson, Bjarni

    2012-01-01

    AIM: To study if and how physicians use the irritable bowel syndrome (IBS) diagnostic criteria and to assess treatment strategies in IBS patients. METHODS: A questionnaire was sent to 191 physicians regarding IBS criteria, diagnostic methods and treatment. Furthermore, 94 patients who were diagnosed with IBS underwent telephone interview. RESULTS: A total of 80/191 (41.9%) physicians responded to the survey. Overall, 13 patients were diagnosed monthly with IBS by specialists in gastroenterology (SGs) and 2.5 patients by general practitioners (GPs). All the SGs knew of the criteria to diagnose IBS, as did 46/70 (65.7%) GPs. Seventy-nine percent used the patient’s history, 38% used a physical examination, and 38% exclusion of other diseases to diagnose IBS. Only 18/80 (22.5%) physicians used specific IBS criteria. Of the patients interviewed, 59/94 (62.8%) knew they had experienced IBS. Two out of five patients knew IBS and had seen a physician because of IBS symptoms. Half of those received a diagnosis of IBS. A total of 13% were satisfied with treatment. IBS affected daily activities in 43% of cases. CONCLUSION: Half of the patients with IBS who consulted a physician received a diagnosis. Awareness and knowledge of diagnostic criteria for IBS differ between SGs and GPs. PMID:22851864

  14. Therapeutic Advances in Functional Gastrointestinal Disease: Irritable Bowel Syndrome

    PubMed Central

    Gaman, Alexandru; Bucur, Maria Cristina

    2009-01-01

    Reported prevalence rates of irritable bowel syndrome (IBS) are between 8% to 20% in the US general population with an average medical expenditure of US$1.35 billion direct and US$205 million indirect costs. Current pathophysiologic theories are based on abnormalities of both the brain and gut, thus setting a new stage for current and future therapeutic approaches. There are numerous treatment options in IBS acting centrally and peripherally by influencing motility and visceral sensitivity. Clinical evidence is variable; however, newer emerging treatments are being evaluated using better-designed clinical trials. Accurate assessment of IBS drug efficacy is still hampered by heterogeneity of the IBS population. Novel methods such as pharmacogenomics or brain imaging may be helpful in the future to better understand and characterize IBS patient subtypes, and this in turn will lead to more specific and efficient therapeutic options. Patient subpopulation measurement of side effects is also a clinical challenge and further understanding could improve treatment efficacy by enhancing the patient compliance. PMID:19936327

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

    PubMed Central

    Hong, Sung Noh; Rhee, Poong-Lyul

    2014-01-01

    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. PMID:24627584

  16. Novel Therapies for Myocardial Irritability following Extreme Hydroxychloroquine Toxicity

    PubMed Central

    McBeth, Paul B.; Missirlis, Perseus I.; Brar, Harry; Dhingra, Vinay

    2015-01-01

    Introduction. Hydroxychloroquine (HCQ) overdose is rare and potentially deadly when consumed in large doses. Management of severe HCQ toxicity is limited and infrequently reported. This report presents the case of a massive ingestion of HCQ. Case Report. A 23-year-old female presents following an intentional ingestion of approximately 40 g of HCQ. Within six hours after ingestion, she developed severe hemodynamic instability resulting from myocardial irritability with frequent ventricular ectopic activity leading to runs of polymorphic ventricular tachycardia (PMVT) and ventricular fibrillation (VF) requiring multiple defibrillations. Additional treatments included intravenous diazepam, epinephrine, norepinephrine, sodium bicarbonate, and magnesium sulfate. Despite the ongoing hemodynamic instability, the patient was also treated with Intralipid (ILE) and received hemodialysis. Improvements in her hemodynamics were observed after 18 hours. She survived her massive overdose of HCQ. Conclusion. HCQ poisoning is rare but serious because of its rapid progression to life-threatening symptoms. Hemodynamic support, gastric decontamination, electrolyte monitoring and replacement, and management of arrhythmias are the mainstays of treatment. The combined role of dialysis and ILE in the setting of massive HCQ overdose may improve outcomes. PMID:26351590

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

    PubMed

    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. PMID:26900286

  18. [Irritable bowel syndrome: diet and complementary medicine therapies?].

    PubMed

    Gerkens, A

    2012-09-01

    Irritable bowel syndrome (IBS) is a frequent and invalidating functional bowel disorder with entangled mechanisms. Its therapeutic approach is therefore complex. Classical therapies, prescribed alone or in combination in light of the predominant symptom, consist of antispasmodics, fibers, laxatives, antidiarrheals, and psychotropic agents. Other emerging pharmacological therapies, such as prokinetics, prosecretory or serotoninergic agents, bile acid modulators and antibiotics have been recently studied in clinical trials. Dietary measures can include reduction of short-chain poorly absorbed carbohydrates (FODMAPs) and gluten restriction. Assessment of food allergy can be proposed in a subgroup of IBS patients. Complementary and alternative medicine therapies, that are generally low cost and safe, appear to be appreciated by patients. Probiotics have demonstrated action on the gut microbiote modulation, and may be helpful in a subset of patients. Peppermint oil has an established visceral analgesic effect. Hypnotherapy represents an original, global and effective approach. Finally, education, reassurance and listening to the patient, leading to a solid therapeutic relationship, represents an essential backdrop of remedy or diet effectiveness. PMID:23091952

  19. Genetic epidemiology and pharmacogenetics in irritable bowel syndrome

    PubMed Central

    Katzka, David A.

    2012-01-01

    The objectives of this review are twofold. Our first objective is to evaluate the evidence supporting a role for genetics in irritable bowel syndrome (IBS). Specific examples of the associations of genetic variation and symptoms, syndromes, and intermediate phenotypes, including neurotransmitter (serotonergic, α2-adrenergic, and cannabinoid) mechanisms, inflammatory pathways (IL-10, TNFα, GNβ3, and susceptibility loci involved in Crohn's disease), and bile acid metabolism, are explored. The second objective is to review pharmacogenetics in IBS, with the focus on cytochrome P-450 metabolism of drugs used in IBS, modulation of motor and sensory responses to serotonergic agents based on the 5-hydroxytryptamine (5-HT) transporter-linked polymorphic region (5-HTTLPR) and 5-HT3 genetic variants, responses to a nonselective cannabinoid agonist (dronabinol) based on cannabinoid receptor (CNR1) and fatty acid amide hydrolase (FAAH) variation, and responses to a bile acid (sodium chenodeoxycholate) and bile acid binding (colesevelam) based on klothoβ (KLB) and fibroblast growth factor receptor 4 (FGFR4) variation. Overall, there is limited evidence of a genetic association with IBS; the most frequently studied association is with 5-HTTLPR, and the most replicated association is with TNF superfamily member 15. Most of the pharmacogenetic associations are reported with intermediate phenotypes in relatively small trials, and confirmation in large clinical trials using validated clinical end points is still required. No published genome-wide association studies in functional gastrointestinal or motility disorders have been published. PMID:22403795

  20. Recent developments in the pathophysiology of irritable bowel syndrome

    PubMed Central

    El-Salhy, Magdy

    2015-01-01

    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. PMID:26167065

  1. [Irritable Bowel Syndrome, Emotion Regulation, and Gut Microbiota].

    PubMed

    Fukudo, Shin

    2016-06-01

    Irritable bowel syndrome (IBS) is defined as a representative functional gastrointestinal disorder which is characterized by chronic or recurrent abdominal pain and/or abdominal discomfort associated with abnormal bowel movement. Gut microbiota are related to the pathophysiology of IBS. In the field of IBS, post-infectious etiology, stress-induced alteration of microbiota, increased mucosal permeability, bacterial overgrowth, disease-specific microbiota, microbial products, and brain-gut interactions are being investigated. In some individuals, IBS develops after recovery from acute gastroenteritis known as post-infectious IBS. Gut microbiota in IBS patients differ from those in healthy individuals, and the profiles of gut microbiota in IBS patients also vary among IBS patients with constipation, diarrhea, and mixed subtypes. In Japan, gut microbiota in IBS patients also differ from those observed in healthy individuals, and organic acid by-products observed in the patients correlated with symptoms, quality of life, and alexithymia. Further research on gut microbiota in IBS patients is warranted. PMID:27279158

  2. Optimal management of constipation associated with irritable bowel syndrome

    PubMed Central

    Furnari, Manuele; de Bortoli, Nicola; Martinucci, Irene; Bodini, Giorgia; Revelli, Matteo; Marabotto, Elisa; Moscatelli, Alessandro; Del Nero, Lorenzo; Savarino, Edoardo; Giannini, Edoardo G; Savarino, Vincenzo

    2015-01-01

    Irritable bowel syndrome (IBS) is a common chronic functional disorder of the gastrointestinal tract, meanly characterized by recurrent abdominal pain or discomfort and altered bowel habit. It is a complex disorder involving biological, environmental, and psychosocial factors. The diagnosis is achieved according to the Rome III criteria provided that organic causes have been excluded. Although IBS does not constitute a life-threatening condition, it has a remarkable prevalence and profoundly reduces the quality of life with burdening socioeconomic costs. One of the principal concerns about IBS is the lack of effective therapeutic options. Up to 40% of patients are not satisfied with any available medications, especially those suffering from chronic constipation. A correct management of IBS with constipation should evolve through a global approach focused on the patient, starting with careful history taking in order to assess the presence of organic diseases that might trigger the disorder. Therefore, the second step is to examine lifestyle, dietary habits, and psychological status. On these bases, a step-up management of disease is recommended: from fiber and bulking agents, to osmotic laxative drugs, to new molecules like lubiprostone and linaclotide. Although new promising tools for relief of bowel-movement-related symptoms are being discovered, a dedicated doctor–patient relationship still seems to be the key for success. PMID:26028974

  3. Diagnosis and treatment of diarrhea-predominant irritable bowel syndrome.

    PubMed

    Lacy, Brian E

    2016-01-01

    Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders worldwide. The economic impact of IBS on the health care system is substantial, as is the personal impact on patients. Patients with diarrhea-predominant IBS (IBS-D) comprise a substantial proportion of the overall IBS population. Primary care providers are often the first point of contact for patients with IBS-D and can accurately diagnose IBS after a careful history and examination without extensive diagnostic tests. Several pharmacologic treatments (eg, loperamide, alosetron, and antidepressants) and non-pharmacologic treatments (eg, dietary modification and probiotics) are available for IBS-D, but restrictions on use (eg, alosetron) or the lack of controlled trial data showing reductions in both global and individual IBS-D symptoms (eg, bloating, pain and stool frequency) emphasize the need for alternative treatment options. Two newer medications (eluxadoline and rifaximin) were approved in May 2015 for the treatment of IBS-D, and represent new treatment options for this common gastrointestinal condition. PMID:26929659

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

    PubMed

    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. PMID:24627581

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

    PubMed

    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. PMID:26139983

  6. Irritable bowel syndrome: the role of gut neuroendocrine peptides.

    PubMed

    El-Salhy, Magdy; Seim, Inge; Chopin, Lisa; Gundersen, Doris; Hatlebakk, Jan Gunnar; Hausken, Trygve

    2012-01-01

    Irritable bowel syndrome (IBS) is a common chronic disorder with a prevalence ranging from 5 to 10 percent of the world's population. This condition is characterised by abdominal discomfort or pain, altered bowel habits, and often bloating and abdominal distension. IBS reduces quality of life in the same degree of impairment as major chronic diseases such as congestive heart failure and diabetes and the economic burden on the health care system and society is high. Abnormalities have been reported in the neuroendocrine peptides/amines of the stomach, small- and large intestine in patients with IBS. These abnormalities would cause disturbances in digestion, gastrointestinal motility and visceral hypersensitivity, which have been reported in patients with IBS. These abnormalities seem to contribute to the symptom development and appear to play a central role in the pathogenesis of IBS. Neuroendocrine peptides/amines are potential tools in the treatment and diagnosis of IBS. In particular, the cell density of duodenal chromogranin A expressing cells appears to be a good histopathological marker for the diagnosis of IBS with high sensitivity and specificity. PMID:22652678

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

    PubMed

    El-Salhy, Magdy

    2015-07-01

    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. PMID:26167065

  8. Rifaximin: The Revolutionary Antibiotic Approach for Irritable Bowel Syndrome.

    PubMed

    Triantafyllou, Konstantinos; Sioulas, Athanasios D; Giamarellos-Bourboulis, Evangelos J

    2015-01-01

    A large number of clinical studies using breath testing and a smaller number of studies using quantitative cultures of the upper small intestine established a link between irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO). A series of 12 studies both prospective and retrospective in design in a population of patients with SIBO without IBS showed that the non-absorbable antibiotic rifaximin can eradicate SIBO as proved through decrease of the exhaled hydrogen and methane in breath tests. The efficacy of rifaximin was superior over the comparator treatment in most of these studies. Based on these findings, short course rifaximin was tested in various concentrations in eight open-label trials in patients with IBS and proven SIBO by breath test. Similar efficacy of rifaximin was shown in SIBO eradication; this was accompanied by improvement of the global score for IBS symptoms. Finally, five double-blind randomized clinical trials were conducted in patients with IBS; four were placebo-controlled. The larger trials were TARGET 1 and TARGET 2 studies testing rifaximin at a regimen of 550 mg tid for 14 days. All trials showed a significant superiority of rifaximin over comparator for the improvement of global symptoms of IBS and bloating. Although the aforementioned results render rifaximin a revolutionary therapeutic approach for IBS, several concerns on induction of antimicrobial resistant flora remain. PMID:26202193

  9. [Bran in the treatment of irritable bowel syndrome].

    PubMed

    Dubinin, A V; Kabanov, A V; Kirkin, B V; Kolkunova, G K; Igorianova, N A

    1987-01-01

    The paper deals with the problem of using wheat bran in the treatment of patients with irritable colon syndrome expressed as spastic constipation. The effectiveness of the treatment with the wheat bran only (in a dose of 30-35 g/day), and in combination with drugs was comparatively studied in 105 patients. The bran fractions differing in the particle size, in the content of cellulose, starch and vitamins were used in the treatment. The combined therapy proved to be advantageous only in the rate of the clinical effect, while the acceleration of the movement along the large intestine did not depend on the treatment type. A long-term (during one year) follow-up of the patients showed that the bran intake led to the cessation of the disease relapse; when the bran was abolished the symptoms of the disease appeared in 11 out of 12 cases. The highest effect was recorded with the bran fraction containing 55.3% cellulose, 18.3% lignin, 157 micrograms tocopherol and the lowest amount of starch--18.0%. A conclusion has been made that the wheat bran are effective in the treatment and prevention of intestinal diseases, the effectiveness of the treatment depends on the summary content of food fibers in the nutrition. PMID:3031879

  10. Celiac disease: Serologic prevalence in patients with irritable bowel syndrome

    PubMed Central

    Mehdi, Zobeiri; Sakineh, Ebrahimi; Mohammad, Farahvash; Mansour, Rezaei; Alireza, Abdollahi

    2012-01-01

    Background: The prevalence of irritable bowel syndrome (IBS) in the community is 10%–20% and have symptom based diagnostic criteria. Many symptoms of celiac disease (CD) with 1% prevalence in some communities can mimic IBS. Sensitive and specific serologic tests of CD can detect asymptomatic cases. The purpose of this study was to compare the level of anti-tissue-transglutaminase (tTG) IgA in IBS patients and controls group. Materials and Methods: This case-control study was performed at a University hospital in which 107 patients with IBS who met the Rome II criteria for their diagnosis were compared with 126 healthy age and sex-matched controls. Both groups were investigated for CD by analysis of their serum tTG IgA antibody with human recombinant antigen. Titers were positive containing over 10u/ml and borderline if they were between 4 and 10 u/ml. Result: 86 percent of IBS patients were female. The mean antibody level was 0.837 u/ml in IBS group and 0.933 u/ml in control group without any significant difference. Discussion and Conclusion: Results of this study may intensify disagreement on the situation of CD in IBS patients. PMID:23826010

  11. Practical management of irritable bowel syndrome: a clinical review.

    PubMed

    Almquist, Ellinor; Törnblom, Hans; Simrén, Magnus

    2016-03-01

    Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder, frequently managed by general practitioners and gastroenterologists. It is a complex condition, characterized by abdominal pain or discomfort associated with altered bowel habits, and it affects 11% of the population worldwide. It has a profound effect on quality of life for many patients and poses a substantial cost to society. Due to the complexity and diversity of IBS, diagnosis and treatment can be challenging. Common drawbacks in diagnosing and treating this disorder include unnecessary tests, failure to establish trust in the physician-patient relationship and difficulties in explaining the diagnosis. Research in recent years has however refined the diagnostic criteria and improved our ability to safely identify IBS with a limited number of investigations. A concise diagnostic evaluation, guided adequate information, prompt initiation of symptom-guided treatment and consistency in the patient-doctor relationship can help relieve the suffering experienced by patients with IBS. For patients with mild symptoms, reassurance, education, lifestyle changes and dietary advice are often sufficient. Patients with moderate to severe symptoms might need symptom modifying drugs, and psychological treatments such as CBT or hypnotherapy may be offered at this stage. For patients with severe and incapacitating symptoms, a multidisciplinary approach is recommended and psychotropic drugs are often used. This clinical review offers suggestions for a diagnostic approach as well as a treatment strategy, based on the current evidence on pathophysiology, diagnosis and treatment in IBS. PMID:26448307

  12. New Receptor Targets for Medical Therapy in Irritable Bowel Syndrome

    PubMed Central

    Camilleri, Michael

    2010-01-01

    Background Despite setbacks to the approval of new medications for the treatment of irritable bowel syndrome, interim guidelines on endpoints for IBS trials have enhanced interest as new targets for medical therapy are proposed based on novel mechanisms or chemical entities. Aim To review the approved lubiprostone, two targets that are not meeting expectations (tachykinins and corticotrophin-releasing hormone), the efficacy and safety of new 5-HT4 agonists, intestinal secretagogues (chloride channel activators, and guanylate cyclase-C agonists), bile acid modulation, anti-inflammatory agents and visceral analgesics. Methods Review of selected articles based on PubMed search and clinically relevant information on mechanism of action, safety, pharmacodynamics, and efficacy Conclusions The spectrum of peripheral targets of medical therapy address chiefly the bowel dysfunction of IBS, and these effects are associated with pain relief. There are less clear targets related to the abdominal pain or visceral sensation in IBS. The new 5-HT4 agonists are more specific than older agents, and show cardiovascular safety to date. Secretory agents have high specificity, low bioavailability, and efficacy. The potential risks of agents “borrowed” from other indications (like hyperlipidemia, inflammatory bowel disease or somatic pain) deserve further study. There is reason for optimism in medical treatment of IBS. PMID:19785622

  13. Irritable bowel syndrome treatment: cognitive behavioral therapy versus medical treatment

    PubMed Central

    Mahvi-Shirazi, Majid; Rasoolzade-Tabatabaei, Sayed-Kazem; Amini, Mohsen

    2012-01-01

    Introduction The study aims to investigate two kinds of treatment in patients suffering from irritable bowel syndrome (IBS) and consequently compares its efficacy on improving the symptoms and mental health of patients; one with just medical treatment and another through a combination of psychotherapy and medical treatment. Material and methods Applying general sampling, 50 IBS patients were selected from among those who used to refer to a Gastroenterology Clinic. After physical and mental evaluations based on ROME-II scale and SCL-90-R questionnaires, the subjects were randomly superseded into: the control group with medical treatment and, the case group with a combination of medical and psychological treatments. The acquired data were then analyzed through t-test and Mann-Whitney U-test. Results The findings show that the mental health of patients receiving cognitive behavioral therapy along with the medical treatment was higher than those of the control group at post-test level. It was observed that the therapy reduces the disability caused by IBS. Comparatively, while the cognitive therapy and medical treatments cured 80% of the patients, those receiving cognitive therapy alone showed an extensive reduction of symptoms. Conclusions Considering the role of cognitive behavioral therapy, it is therefore recommend that such patients be managed by a combined team of gastroenterologists and psychologists. PMID:22457686

  14. Treatment of irritable bowel syndrome in China: A review

    PubMed Central

    Li, Chun-Yan; Li, Shu-Chuen

    2015-01-01

    Irritable bowel syndrome (IBS) is a common, chronic, functional gastrointestinal disorder with a high incidence rate in the general population, and it is common among the Chinese population. The pathophysiology, etiology and pathogenesis of IBS are poorly understood, with no evidence of inflammatory, anatomic, metabolic, or neoplastic factors to explain the symptoms. Treatment approaches are mainly focused on symptom management to maintain everyday functioning and to improve quality of life for patients with IBS. However, prescribed medications often result in significant side effects, and many IBS sufferers (particularly Chinese) do not improve. Instead of taking a variety of conventional medications, many have turned to taking traditional Chinese medicine or integrated Chinese and Western medicine for remedy. A number of clinical trials have shown that Chinese herbal, acupuncture or integrative therapies presented improved treatment outcomes and reduced side effects in IBS patients. The purpose of this review article is to examine the treatment approaches of IBS that have been published in recent years, especially in China, to assess the possible differences in treating IBS between China and other countries. This would provide some useful information of unique treatment approach in clinical practice for physicians in the management of IBS in China, thus offering more treatment options for IBS patients with potentially better treatment outcomes while reducing the medical cost burden. PMID:25741137

  15. Personality traits and emotional patterns in irritable bowel syndrome.

    PubMed

    Muscatello, Maria Rosaria A; Bruno, Antonio; Mento, Carmela; Pandolfo, Gianluca; Zoccali, Rocco A

    2016-07-28

    The review focuses on those personality traits (neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness), constructs (alexithymia and distressed - Type D personality) and emotional patterns (negative and positive) that are of particular concern in health psychology, with the aim to highlight their potential role on the pathogenesis, onset, symptom clusters, clinical course, and outcome of irritable bowel syndrome (IBS). Personality traits and emotional patterns play key roles in affecting autonomic, immune, inflammatory, and endocrine functions, thus contributing not only to IBS clinical expression and symptomatic burden, but also to disease physiopathology. In this sense, psychological treatments should address those personality traits and emotional features that are constitutive of, and integral to IBS. The biopsychosocial model of illness applied to IBS acknowledges the interaction between biological, psychological, environmental, and social factors in relation to pain and functional disability. A holistic approach to IBS should take into account the heterogeneous nature of the disorder, and differentiate treatments for different types of IBS, also considering the marked individual differences in prevalent personality traits and emotional patterns. Beyond medications, and lifestyle/dietary interventions, psychological and educational treatments may provide the optimal chance of addressing clinical symptoms, comorbid conditions, and quality of life in IBS patients. PMID:27605876

  16. Diagnosis and treatment of diarrhea-predominant irritable bowel syndrome

    PubMed Central

    Lacy, Brian E

    2016-01-01

    Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders worldwide. The economic impact of IBS on the health care system is substantial, as is the personal impact on patients. Patients with diarrhea-predominant IBS (IBS-D) comprise a substantial proportion of the overall IBS population. Primary care providers are often the first point of contact for patients with IBS-D and can accurately diagnose IBS after a careful history and examination without extensive diagnostic tests. Several pharmacologic treatments (eg, loperamide, alosetron, and antidepressants) and non-pharmacologic treatments (eg, dietary modification and probiotics) are available for IBS-D, but restrictions on use (eg, alosetron) or the lack of controlled trial data showing reductions in both global and individual IBS-D symptoms (eg, bloating, pain and stool frequency) emphasize the need for alternative treatment options. Two newer medications (eluxadoline and rifaximin) were approved in May 2015 for the treatment of IBS-D, and represent new treatment options for this common gastrointestinal condition. PMID:26929659

  17. New and Emerging Treatment Options for Irritable Bowel Syndrome

    PubMed Central

    Lacy, Brian E.; Chey, William D.; Lembo, Anthony J.

    2015-01-01

    Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with abdominal pain, diarrhea, constipation, or a mix of symptoms. The pathophysiology of IBS is not completely understood but appears to involve genetics, the gut microbiome, immune activation, altered intestinal permeability, and brain-gut interactions. There is no gold standard for diagnosis. Several sets of symptom-based guidelines exist. Treatment strategies for IBS may include both nonpharmacologic and pharmacologic approaches. Lifestyle modifications that aim to improve exercise, sleep, diet, and stress may be warranted. Recent data suggest that a gluten-free diet and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) may benefit some patients. For patients with diarrhea-predominant IBS, treatment options include the synthetic peripheral μ-opioid receptor agonist loperamide, antispasmodic agents, antidepressants, serotonin 5-HT3 antagonists, and the gut-specific antibiotic rifaximin. Ongoing research is evaluating the use of probiotics. For patients with constipation-predominant IBS, therapeutic strategies may include dietary fiber, laxatives, and the prosecretory agents lubiprostone and linaclotide. Research is continuing to optimize the use of available agents and evaluating new approaches to further improve the care of patients with IBS. PMID:26491416

  18. An assessment of air quality reflecting the chemosensory irritation impact of mixtures of volatile organic compounds.

    PubMed

    Abraham, Michael H; Gola, Joelle M R; Cometto-Muñiz, J Enrique

    2016-01-01

    We present a method to assess the air quality of an environment based on the chemosensory irritation impact of mixtures of volatile organic compounds (VOCs) present in such environment. We begin by approximating the sigmoid function that characterizes psychometric plots of probability of irritation detection (Q) versus VOC vapor concentration to a linear function. First, we apply an established equation that correlates and predicts human sensory irritation thresholds (SIT) (i.e., nasal and eye irritation) based on the transfer of the VOC from the gas phase to biophases, e.g., nasal mucus and tear film. Second, we expand the equation to include other biological data (e.g., odor detection thresholds) and to include further VOCs that act mainly by "specific" effects rather than by transfer (i.e., "physical") effects as defined in the article. Then we show that, for 72 VOCs in common, Q values based on our calculated SITs are consistent with the Threshold Limit Values (TLVs) listed for those same VOCs on the basis of sensory irritation by the American Conference of Governmental Industrial Hygienists (ACGIH). Third, we set two equations to calculate the probability (Qmix) that a given air sample containing a number of VOCs could elicit chemosensory irritation: one equation based on response addition (Qmix scale: 0.00 to 1.00) and the other based on dose addition (1000*Qmix scale: 0 to 2000). We further validate the applicability of our air quality assessment method by showing that both Qmix scales provide values consistent with the expected sensory irritation burden from VOC mixtures present in a wide variety of indoor and outdoor environments as reported on field studies in the literature. These scales take into account both the concentration of VOCs at a particular site and the propensity of the VOCs to evoke sensory irritation. PMID:26550706

  19. Development of a cumulative irritation model for incontinence-associated dermatitis.

    PubMed

    Larner, J; Matar, H; Goldman, V S; Chilcott, R P

    2015-01-01

    Incontinence-associated dermatitis (IAD) is a painful yet preventable form of cumulative skin irritation prevalent amongst those with limited movement. Consequently, it has a significant impact on the quality of life for those affected as well as substantial cost implications. Prevention and intervention is typically through good skin hygiene regimes and regular use of barrier products. In this paper, we describe the development of an in vivo model of IAD in healthy volunteers by occluded application of alkaline synthetic urine to the volar aspect of volunteer's forearms for 6 h per day over a five-day period to reproduce the moist and irritant conditions causative of IAD. Irritation was assessed and quantified on a daily basis by a series of non-invasive biophysical measurements and compared to a contralateral saline-treated (control) site. Dermal irritation was assessed by subjective (visual) and objective measurements (laser Doppler and polarisation spectroscopic imaging, infrared thermography, skin reflectance spectroscopy, transepidermal water loss and skin surface pH). The provocation of reproducible, cumulative skin irritation was successfully demonstrated and quantified. This five-day model of irritation is considered appropriate for the initial clinical assessment of topical products to prevent or treat IAD. PMID:25416151

  20. An in silico expert system for the identification of eye irritants.

    PubMed

    Verma, R P; Matthews, E J

    2015-01-01

    This report describes development of an in silico, expert rule-based method for the classification of chemicals into irritants or non-irritants to eye, as defined by the Draize test. This method was developed to screen data-poor cosmetic ingredient chemicals for eye irritancy potential, which is based upon exclusion rules of five physicochemical properties - molecular weight (MW), hydrophobicity (log P), number of hydrogen bond donors (HBD), number of hydrogen bond acceptors (HBA) and polarizability (Pol). These rules were developed using the ADMET Predictor software and a dataset of 917 eye irritant chemicals. The dataset was divided into 826 (90%) chemicals used for training set and 91 (10%) chemicals used for external validation set (every 10th chemical sorted by molecular weight). The sensitivity of these rules for the training and validation sets was 72.3% and 71.4%, respectively. These rules were also validated for their specificity using an external validation set of 2011 non-irritant chemicals to the eye. The specificity for this validation set was revealed as 77.3%. This method facilitates rapid screening and prioritization of data poor chemicals that are unlikely to be tested for eye irritancy in the Draize test. PMID:25967253

  1. Efficacy and tolerability of pharmacotherapy options for the treatment of irritability in autistic children.

    PubMed

    Kirino, Eiji

    2014-01-01

    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. PMID:24932108

  2. Potential irritation of lysine derivative surfactants by hemolysis and HaCaT cell viability.

    PubMed

    Sanchez, L; Mitjans, M; Infante, M R; Vinardell, M P

    2006-02-01

    Surfactants represent one of the most common constituents in topical pharmaceutical and cosmetic applications or cleansers. Since adverse skin and ocular reactions can be caused by them, it is important to evaluate damaging effects. Amino acid-based surfactants deserve particular attention because of their low toxicity and environmental friendly properties. New lysine derivative surfactants associated with heavy and light counterions were tested. The ocular irritancy was assessed by hemolysis, and photohemolysis was employed to evaluate their phototoxicity. Cytotoxicity on HaCaT cells was determined by neutral red uptake and MTT assay to predict skin irritation. All lysine derivative surfactants were less hemolytic and thus less eye-irritating than the commercial surfactants used as model irritants. No phototoxic effects were found. All surfactants presented cytotoxic effects as demonstrated by decrease of neutral red uptake and reduction of MTT salt, with clear concentration-effect profiles. However, the rates of cytotoxicity on HaCaT for the new surfactants suggested that they were less cytotoxic and then, less skin-irritating than the reference ones; surfactants with heavy counterions were the less cytotoxic. The anionic surfactants investigated in the present work may constitute a promising class of surfactants given their low irritancy potential for pharmaceutical and cosmetic preparations. PMID:16135402

  3. Ocular irritation from product of pesticide degradation among workers in a seed warehouse

    PubMed Central

    MATSUKAWA, Takehisa; YOKOYAMA, Kazuhito; ITOH, Hiroaki

    2014-01-01

    Four workers at a seed supply warehouse in Chiba Prefecture, Japan, complained of ocular irritation on the job. Pesticide-coated seeds were stored in the warehouse but no significant amount of pesticide was detected in the air inside the warehouse. To identify the cause of the ocular irritation and to determine an appropriate solution to the problem, the authors used thermal desorption gas chromatography-mass spectrometry to analyze the profiles of volatile organic compounds (VOCs) in the air of the two warehouses at the site—warehouse A, where the four workers experienced ocular irritation, and warehouse B, where no workers experienced ocular irritation. Comparing the profiles of VOCs in these warehouses indicated that n-butyl isocyanate, a hydrolyzed product of the fungicide benomyl, was the cause of the workers’ ocular irritation. n-Butyl isocyanate is known to be a contact irritant and if the benomyl-coated seeds were not properly dried before storage in the warehouse n-butyl isocyanate would have been produced. The results of the study suggest that more attention should be paid both to the pesticide itself and to the products of pesticide degradation. In this study, n-butyl isocyanate was identified as a product of pesticide degradation and a causative chemical affecting occupational health. PMID:25327297

  4. Sensitizing and irritant properties of 3 environmental classes of diesel oil and their indicator dyes.

    PubMed

    Fischer, T; Bjarnason, B

    1996-05-01

    3 dyes, Solvent Yellow 124 and Solvent Blue 79 or Solvent Blue 98, were added to diesel oils in Sweden for identification of their particular use and taxation bracket in late 1993. Health concern regarding the toxicity of the dyes resulted in several reports to the Worker Inspection Bureau. 36 men reporting skin disease supposedly caused by dyes were diagnosed to have irritant reactions, irritant contact dermatitis or exacerbation of other skin disease. Tests on 15 individuals from this group, and 20 healthy volunteers, failed to demonstrate contact allergy or contact urticaria to the dyes or dyed diesel oil. Patch tests with dyes (10% v/v) in pet. did not cause irritation. Tests of irritant properties of the diesel oils showed that the old type of oil, with high viscosity, high content or aromatic compounds and moderately high sulfur content, caused little irritation, whereas newer, lighter qualities of diesel oil, with low concentrations of aromatic compounds and low sulfur content, which cause less pollution to the environment when burnt, were significantly more irritant to the skin and probably a cause of the skin problems. PMID:8807221

  5. Assessment of skin and eye irritation of 14 products under the stepwise approach of the OECD.

    PubMed

    Mancebo, Axel; Hernández, Osvaldo; González, Yana; Aldana, Lizet; Carballo, Onelio

    2008-01-01

    The determination of acute eye and skin irritation is included in international regulatory requirements for the testing of chemicals, because of the possibility of exposure during the production, transport, marketing, and disposal of products. Although there have been some advances in the areas of refinement and reduction, no single battery of tests has emerged as being acceptable as a complete replacement for the conventional Draize rabbit eye and skin irritation tests. Currently, dermal irritation and ocular irritation are generally evaluated in a sequential manner in the context of tiered assessment strategies. In this work, we show how 14 products, mostly designed to be used in agriculture, were evaluated in the Center of Experimental Toxicology of the Center for the Production of Laboratory Animals (Centro Nacional para la Producción de Animales de Laboratorio; CENPALAB) in order to assess their acute dermal and ocular effects. The performed studies include the acute dermal toxicity test, the acute dermal irritation/corrosion test, the hen's egg test-chorioallantoic membrane (HET-CAM) method, and the acute eye irritation/corrosion test. In general, it could be concluded that of the 14 products assessed, none of them showed systemic effects, but local reactions mainly to the eyes. The most significant effects were apparently related to the effects of azadirachtin, an active principle of 2 tested neem derivatives. PMID:18988087

  6. Microbial community and metabolomic comparison of irritable bowel syndrome faeces.

    PubMed

    Ponnusamy, Kannan; Choi, Jung Nam; Kim, Jiyoung; Lee, Sun-Young; Lee, Choong Hwan

    2011-06-01

    Human health relies on the composition of microbiota in an individual's gut and the synthesized metabolites that may alter the gut environment. Gut microbiota and faecal metabolites are involved in several gastrointestinal diseases. In this study, 16S rRNA-specific denaturing gradient gel electrophoresis and quantitative PCR analysis showed that the mean similarity of total bacteria was significantly different (P<0.001) in faecal samples from patients with irritable bowel syndrome (IBS; n = 11) and from non-IBS (nIBS) patients (n = 8). IBS subjects had a significantly higher diversity of total bacteria, as measured by the Shannon index (H') (3.360.05). GC/MS-based multivariate analysis delineated the faecal metabolites of IBS from nIBS samples. Elevated levels of amino acids (alanine and pyroglutamic acid) and phenolic compounds (hydroxyphenyl acetate and hydroxyphenyl propionate) were found in IBS. These results were highly correlated with the abundance of lactobacilli and Clostridium, which indicates an altered metabolism rate associated with these gut micro-organisms. A higher diversity of Bacteroidetes and Lactobacillus groups in IBS faecal samples also correlated with the respective total quantity. In addition, these changes altered protein and carbohydrate energy metabolism in the gut. PMID:21330412

  7. Role of antispasmodics in the treatment of irritable bowel syndrome

    PubMed Central

    Annaházi, Anita; Róka, Richárd; Rosztóczy, András; Wittmann, Tibor

    2014-01-01

    Irritable bowel syndrome (IBS) is a long-lasting, relapsing disorder characterized by abdominal pain/discomfort and altered bowel habits. Intestinal motility impairment and visceral hypersensitivity are the key factors among its multifactorial pathogenesis, both of which require effective treatment. Voltage-gated calcium channels mediate smooth muscle contraction and endocrine secretion and play important roles in neuronal transmission. Antispasmodics are a group of drugs that have been used in the treatment of IBS for decades. Alverine citrate, a spasmolytic, decreases the sensitivity of smooth muscle contractile proteins to calcium, and it is a selective 5-HT1A receptor antagonist. Alverine, in combination with simethicone, has been demonstrated to effectively reduce abdominal pain and discomfort in a large placebo-controlled trial. Mebeverine is a musculotropic agent that potently blocks intestinal peristalsis. Non-placebo-controlled trials have shown positive effects of mebeverine in IBS regarding symptom control; nevertheless, in recent placebo-controlled studies, mebeverine did not exhibit superiority over placebo. Otilonium bromide is poorly absorbed from the GI tract, where it acts locally as an L-type calcium channel blocker, an antimuscarinic and a tachykinin NK2 receptor antagonist. Otilonium has effectively reduced pain and improved defecation alterations in placebo-controlled trials in IBS patients. Pinaverium bromide is also an L-type calcium channel blocker that acts locally in the GI tract. Pinaverium improves motility disorders and consequently reduces stool problems in IBS patients. Phloroglucinol and trimethylphloroglucinol are non-specific antispasmodics that reduced pain in IBS patients in a placebo-controlled trial. Antispasmodics have excellent safety profiles. T-type calcium channel blockers can abolish visceral hypersensitivity in animal models, which makes them potential candidates for the development of novel therapeutic agents in the

  8. Anti-Enteric Neuronal Antibodies and the Irritable Bowel Syndrome

    PubMed Central

    Liu, Sumei; Drossman, Douglas A; Ringel, Yehuda; Whitehead, William E

    2012-01-01

    Background/Aims Functional gastrointestinal disorders are those in which no abnormal metabolic or physical processes, which can account for the symptoms, can be identified. The irritable bowel syndrome (IBS) is a significant functional disorder, which affects 10-20 percent of the population worldwide. Predominant symptoms of IBS are abnormal defecation associated with abdominal pain, both of which may be exacerbated by psychogenic stress. Our study was designed to test a hypothesis that symptoms in a subset of patients with a diagnosis of IBS are associated with an autoimmune degenerative neuropathy in the enteric nervous system. Methods Serum was collected from Rome II-IBS patients and controls at the University of North Carolina Functional Gastrointestinal Diseases Center. Assay procedures were immunohistochemical localization of antibody binding to enteric neurons and human protein microarray assay for antigens recognized by antibodies in the sera. Results Eighty-seven percent of IBS sera and 59% of control sera contained anti-enteric neuronal antibodies. Antibody immunostaining was seen in the nucleus and cytoplasm of neurons in the enteric nervous system. Protein microarray analysis detected antibody reactivity for autoantigens in serum with anti-enteric neuronal antibodies and no reactivity for the same autoantigens in samples not containing anti-enteric neuronal antibodies in our immunostaining assay. Antibodies in sera from IBS patients recognized only 3 antigens out of an 8,000 immunoprotein array. The 3 antigens were: (1) a nondescript ribonucleoprotein (RNP-complex); (2) small nuclear ribonuclear polypeptide A; and (3) Ro-5,200 kDa. Conclusions Results of the present study suggest that symptoms in a subset of IBS patients might be a reflection of enteric neuronal damage or loss, caused by circulating anti-enteric autoimmune antibodies. PMID:22323991

  9. Role of opioid ligands in the irritable bowel syndrome.

    PubMed

    Corazziari, E

    1999-03-01

    Endogenous opioid peptides - enkephalins, beta-endorphin and dynorphins - are located in specific sites of the brain, the spinal cord, the autonomic ganglia and the enteric nervous system. Endogenous opioids participate in the regulation of nervous visceral afference and sensitivity as well as of several visceral motor function induced by the central nervous system and through the enteroenteric and the myoenteric reflexes. Their final effect on gut physiology is the net and harmonically balanced result of their binding to mu, delta and kappa opioid receptor subtypes. Exogenous opioid receptor ligands with different affinities for the opioid receptor subtypes have been effectively used to modify and normalize altered gut functions. The mu receptor agonists - morphine and, to a greater extent, the meperidine congeners diphenoxylate and loperamide - have been shown to slow gastrointestinal transit by their effects on the circular and longitudinal muscle of the intestine. Diphenoxylate and, more efficiently, loperamide, for the lack of any effect on the central nervous system, have been usefully employed in the treatment of diarrhea in irritable bowel syndrome (IBS) patients. Unlike the mu receptor agonists morphine and loperamide, which invariably stimulate colonic motility, trimebutine, which has almost equal affinity for mu, delta and kappa receptors, has no effect on normal colonic activity but reduces the abnormal increase in postprandial motor activity in IBS patients and accelerates slow large bowel transit in constipated patients. Opioid ligands can be usefully employed to normalize altered visceral sensitivity in IBS patients. The kappa receptor agonist fedotozine exerts its antinociceptive effect by acting on peripheral nerve endings of sensory vagal and nonvagal afferent pathways. Fedotozine has been shown to increase the threshold of perception to colonic distension in experimental conditions and to affect favourably symptoms of IBS in clinical trials. PMID

  10. Modern Management of Irritable Bowel Syndrome: More Than Motility.

    PubMed

    Tack, Jan; Vanuytsel, Tim; Corsetti, Maura

    2016-01-01

    In the treatment of irritable bowel syndrome (IBS), loperamide seems efficacious for diarrhea and ispaghula for constipation, while musculotropic spasmolytics may relieve abdominal pain. Antidepressants were found to be efficacious for abdominal pain, but their tolerance may be problematic and the therapeutic effect varied largely between trials. While meta-analyses suggest efficacy of probiotics as a group, the quality of the trials is often suboptimal and there is large variability. Lubiprostone, a chloride channel activator, and linaclotide, a guanylyl cyclase-C agonist, showed favorable effects on multiple symptoms in IBS with constipation. For IBS with diarrhea (IBS-D), the 5-HT3 receptor antagonist ramosetron showed efficacy in men and women, but is currently only approved in Japan. A multicenter study with the anti-emetic 5-HT3 receptor antagonist ondansetron showed efficacy on stool pattern in IBS-D. The poorly absorbable antibiotic rifaximin and eluxadoline, a mu opioid receptor agonist and delta antagonist, both showed efficacy in phase III trials in IBS-D and were approved by the FDA. Eluxadoline was associated with increased occurrence of sphincter of Oddi spasm and biliary pancreatitis. The non-pharmacological treatment of IBS, with dietary interventions (mainly gluten elimination and low FODMAP (fructose, oligo-, di-, monosaccharides and polyols)) has received a lot of attention lately. While responder rates vary across studies, perhaps based on regional variations in dietary intake of FODMAPs, the dietary approach seems to have acquired recognition as a valid therapeutic alternative. Long-term studies and comparative studies with pharmacotherapy, as well as elucidation of the underlying mechanisms of action, are needed. PMID:27331917

  11. Treatment of abdominal pain in irritable bowel syndrome.

    PubMed

    Vanuytsel, Tim; Tack, Jan F; Boeckxstaens, Guy E

    2014-08-01

    Functional abdominal pain in the context of irritable bowel syndrome (IBS) is a challenging problem for primary care physicians, gastroenterologists and pain specialists. We review the evidence for the current and future non-pharmacological and pharmacological treatment options targeting the central nervous system and the gastrointestinal tract. Cognitive interventions such as cognitive behavioral therapy and hypnotherapy have demonstrated excellent results in IBS patients, but the limited availability and labor-intensive nature limit their routine use in daily practice. In patients who are refractory to first-line therapy, tricyclic antidepressants (TCA) and selective serotonin reuptake inhibitors are both effective to obtain symptomatic relief, but only TCAs have been shown to improve abdominal pain in meta-analyses. A diet low in fermentable carbohydrates and polyols (FODMAP) seems effective in subgroups of patients to reduce abdominal pain, bloating, and to improve the stool pattern. The evidence for fiber is limited and only isphagula may be somewhat beneficial. The efficacy of probiotics is difficult to interpret since several strains in different quantities have been used across studies. Antispasmodics, including peppermint oil, are still considered the first-line treatment for abdominal pain in IBS. Second-line therapies for diarrhea-predominant IBS include the non-absorbable antibiotic rifaximin and the 5HT3 antagonists alosetron and ramosetron, although the use of the former is restricted because of the rare risk of ischemic colitis. In laxative-resistant, constipation-predominant IBS, the chloride-secretion stimulating drugs lubiprostone and linaclotide, a guanylate cyclase C agonist that also has direct analgesic effects, reduce abdominal pain and improve the stool pattern. PMID:24845149

  12. Latent structure of irritable bowel syndrome symptom severity

    PubMed Central

    Jasper, Fabian; Egloff, Boris; Roalfe, Andrea; Witthöft, Michael

    2015-01-01

    AIM: To investigate the latent structure of an irritable bowel syndrome (IBS) symptom severity scale in a population of healthy adults. METHODS: The Birmingham IBS symptom questionnaire which consists of three symptom specific scales (diarrhea, constipation, pain) was evaluated by means of structural equation modeling. We compared the original 3-factor solution to a general factor model and a bifactor solution in a large internet sample of college students (n = 875). Statistical comparisons of competing models were conducted by means of χ2 difference tests. Regarding the evaluation of model fit, we examined the comparative fit index (CFI) and the Root Mean Square Error of Approximation (RMSEA). RESULTS: Results clearly favored a bifactor model of IBS symptom severity (CFI = 0.99, RMSEA = 0.05) which consisted of a strong general IBS somatization factor and three symptom specific factors (diarrhea, constipation, pain) based on the subscales of the Birmingham IBS symptom questionnaire. The fit indices of the competing one factor model (CFI = 0.85, RMSEA = 0.17) and three factor model (CFI = 0.97, RMSEA = 0.08) were clearly inferior. χ2 difference tests showed that the differences between the models were indeed significant in favor of the bifactor model (P < 0.001). Correlations of the four latent factors with measures of pain sensitivity, somatoform dissociation, fatigue severity, and demographic variables support the validity of our bifactor model of IBS specific symptom severity. CONCLUSION: The findings suggest that IBS symptom severity might best be understood as a continuous and multidimensional construct which can be reliably and validly assessed with the B-IBS. PMID:25574104

  13. Role of antispasmodics in the treatment of irritable bowel syndrome.

    PubMed

    Annaházi, Anita; Róka, Richárd; Rosztóczy, András; Wittmann, Tibor

    2014-05-28

    Irritable bowel syndrome (IBS) is a long-lasting, relapsing disorder characterized by abdominal pain/discomfort and altered bowel habits. Intestinal motility impairment and visceral hypersensitivity are the key factors among its multifactorial pathogenesis, both of which require effective treatment. Voltage-gated calcium channels mediate smooth muscle contraction and endocrine secretion and play important roles in neuronal transmission. Antispasmodics are a group of drugs that have been used in the treatment of IBS for decades. Alverine citrate, a spasmolytic, decreases the sensitivity of smooth muscle contractile proteins to calcium, and it is a selective 5-HT1A receptor antagonist. Alverine, in combination with simethicone, has been demonstrated to effectively reduce abdominal pain and discomfort in a large placebo-controlled trial. Mebeverine is a musculotropic agent that potently blocks intestinal peristalsis. Non-placebo-controlled trials have shown positive effects of mebeverine in IBS regarding symptom control; nevertheless, in recent placebo-controlled studies, mebeverine did not exhibit superiority over placebo. Otilonium bromide is poorly absorbed from the GI tract, where it acts locally as an L-type calcium channel blocker, an antimuscarinic and a tachykinin NK2 receptor antagonist. Otilonium has effectively reduced pain and improved defecation alterations in placebo-controlled trials in IBS patients. Pinaverium bromide is also an L-type calcium channel blocker that acts locally in the GI tract. Pinaverium improves motility disorders and consequently reduces stool problems in IBS patients. Phloroglucinol and trimethylphloroglucinol are non-specific antispasmodics that reduced pain in IBS patients in a placebo-controlled trial. Antispasmodics have excellent safety profiles. T-type calcium channel blockers can abolish visceral hypersensitivity in animal models, which makes them potential candidates for the development of novel therapeutic agents in the

  14. The microbiome of the oral mucosa in irritable bowel syndrome

    PubMed Central

    Fourie, Nicolaas H.; Wang, Dan; Abey, Sarah K.; Sherwin, LeeAnne B.; Joseph, Paule V.; Rahim-Williams, Bridgett; Ferguson, Eric G.; Henderson, Wendy A.

    2016-01-01

    abstract Irritable bowel syndrome (IBS) is a poorly understood disorder characterized by persistent symptoms, including visceral pain. Studies have demonstrated oral microbiome differences in inflammatory bowel diseases suggesting the potential of the oral microbiome in the study of non-oral conditions. In this exploratory study we examine whether differences exist in the oral microbiome of IBS participants and healthy controls, and whether the oral microbiome relates to symptom severity. The oral buccal mucosal microbiome of 38 participants was characterized using PhyloChip microarrays. The severity of visceral pain was assessed by orally administering a gastrointestinal test solution. Participants self-reported their induced visceral pain. Pain severity was highest in IBS participants (P = 0.0002), particularly IBS-overweight participants (P = 0.02), and was robustly correlated to the abundance of 60 OTUs, 4 genera, 5 families and 4 orders of bacteria (r2 > 0.4, P < 0.001). IBS-overweight participants showed decreased richness in the phylum Bacteroidetes (P = 0.007) and the genus Bacillus (P = 0.008). Analysis of β-diversity found significant separation of the IBS-overweight group (P < 0.05). Our oral microbial results are concordant with described fecal and colonic microbiome-IBS and -weight associations. Having IBS and being overweight, rather than IBS-subtypes, was the most important factor in describing the severity of visceral pain and variation in the microbiome. Pain severity was strongly correlated to the abundance of many taxa, suggesting the potential of the oral microbiome in diagnosis and patient phenotyping. The oral microbiome has potential as a source of microbial information in IBS. PMID:26963804

  15. Possible pathogenetic roles of abdominal surgery in irritable bowel syndrome.

    PubMed

    Li, Sen; Yu, Yifeng; Prakash, Ravi

    2011-04-01

    Recently, a plethora of studies have reported that irritably bowel syndrome (IBS) patients have increased incidences of abdominal surgeries, mainly gut surgeries. This high incidence of surgeries highlights the fact that the surgery was done because diagnosis of IBS was not suspected in them. It is then a matter of inquisitiveness as to why the diagnosis of IBS was missed in so many patients. Lack of clinical diagnostic sophistication could be one of the reasons. However, inspite of these facts, it has never been documented that the typical IBS like picture was present in these patients before surgery. Mostly, the preoperative complaints in negative appendectomy patients have been atypical pain syndromes. Thus we should also take into account the possibility that the typical IBS symptom profile was not present in these patients before surgery and that the surgical intervention could have resulted in subsequent development of complete picture of IBS. Infact, in one study, various surgical procedures were known to precede IBS symptoms, where they have also been conceptualized as one of the stressors which could lead to IB. Seeing from the other perspective, the etiological understanding of IBS in medical literature is still so preliminary that we have only been able to enumerate some possible factors. In such a scenario, we need to explore in detail the events which occur frequently in IBS patients, like abdominal surgery. Here, we hypothesize that any abdominal surgical intervention could itself be a reason for development of IBS. We provide evidences from literature in favor of two such possible mechanisms through which any abdominal surgical procedure could act resulting in development of IBS. In addition, we present the report of follow-up of 4 of our own patients where we specifically inquired about IBS before the appendectomy, which turned out to be negative. After 6 months of the followup, the patients developed symptoms which were diagnosable as IBS. PMID

  16. Evaluation of drug treatment in irritable bowel syndrome

    PubMed Central

    Talley, Nicholas J

    2003-01-01

    The irritable bowel syndrome (IBS) remains a therapeutic challenge in part because of the limited understanding of the pathophysiology. The placebo response rate varies in randomized controlled trials from 20 to 70%, and can persist for up to at least 1 year. It is contentious whether dietary fibre and bulking agents relieve the symptoms of IBS; constipation probably improves. Anticholinergic and antispasmodic agents are of questionable benefit in IBS despite positive meta-analyses of poor quality trials. A meta-analysis concluded that the tricyclic antidepressants were superior to placebo in IBS, although the individual trial results were variable. Selective serotonin reuptake inhibitors are of uncertain benefit. Laxatives are used for constipation but probably poorly control the IBS symptom complex. Loperamide is superior to placebo in improvement of diarrhoea but not abdominal pain in IBS. Tegaserod is a well- tolerated aminoguanidine indole derivative of serotonin that is a partial 5HT4–receptor agonist with prokinetic properties; a therapeutic gain over placebo of 5% to 15% has been observed in constipation-predominant IBS in females. Alosetron is a 5HT3-receptor antagonist that is efficacious in females with diarrhoea-predominant IBS, with a 12% to 17% therapeutic gain; the risk of ischaemic colitis is 1 in 350, with very severe constipation occurring in about 1 in 1000. Optimizing study design remains a challenge in IBS. New visceral analgesic and motility modifying agents, as well as anti-inflammatory agents are in trials, and hopefully additional efficacious therapeutic options for patients with IBS will soon emerge. PMID:12968980

  17. The involvement of TRP channels in sensory irritation: a mechanistic approach toward a better understanding of the biological effects of local irritants.

    PubMed

    Lehmann, Ramona; Schöbel, Nicole; Hatt, Hanns; van Thriel, Christoph

    2016-06-01

    Peripheral nerves innervating the mucosae of the nose, mouth, and throat protect the organism against chemical hazards. Upon their stimulation, characteristic perceptions (e.g., stinging and burning) and various reflexes are triggered (e.g., sneezing and cough). The potency of a chemical to cause sensory irritation can be estimated by a mouse bioassay assessing the concentration-dependent decrease in the respiratory rate (50 % decrease: RD50). The involvement of the N. trigeminus and its sensory neurons in the irritant-induced decrease in respiratory rates are not well understood to date. In calcium imaging experiments, we tested which of eight different irritants (RD50 5-730 ppm) could induce responses in primary mouse trigeminal ganglion neurons. The tested irritants acetophenone, 2-ethylhexanol, hexyl isocyanate, isophorone, and trimethylcyclohexanol stimulated responses in trigeminal neurons. Most of these responses depended on functional TRPA1 or TRPV1 channels. For crotyl alcohol, 3-methyl-1-butanol, and sodium metabisulfite, no activation could be observed. 2-ethylhexanol can activate both TRPA1 and TRPV1, and at low contractions (100 µM) G protein-coupled receptors (GPCRs) seem to be involved. GPCRs might also be involved in the mediation of the responses to trimethylcyclohexanol. By using neurobiological tools, we showed that sensory irritation in vivo could be based on the direct activation of TRP channels but also on yet unknown interactions with GPCRs present in trigeminal neurons. Our results showed that the potency suggested by the RD50 values was not reflected by direct nerve-compound interaction. PMID:27037703

  18. Predictive performance of the Vitrigel-eye irritancy test method using 118 chemicals.

    PubMed

    Yamaguchi, Hiroyuki; Kojima, Hajime; Takezawa, Toshiaki

    2016-08-01

    We recently developed a novel Vitrigel-eye irritancy test (EIT) method. The Vitrigel-EIT method is composed of two parts, i.e., the construction of a human corneal epithelium (HCE) model in a collagen vitrigel membrane chamber and the prediction of eye irritancy by analyzing the time-dependent profile of transepithelial electrical resistance values for 3 min after exposing a chemical to the HCE model. In this study, we estimated the predictive performance of Vitrigel-EIT method by testing a total of 118 chemicals. The category determined by the Vitrigel-EIT method in comparison to the globally harmonized system classification revealed that the sensitivity, specificity and accuracy were 90.1%, 65.9% and 80.5%, respectively. Here, five of seven false-negative chemicals were acidic chemicals inducing the irregular rising of transepithelial electrical resistance values. In case of eliminating the test chemical solutions showing pH 5 or lower, the sensitivity, specificity and accuracy were improved to 96.8%, 67.4% and 84.4%, respectively. Meanwhile, nine of 16 false-positive chemicals were classified irritant by the US Environmental Protection Agency. In addition, the disappearance of ZO-1, a tight junction-associated protein and MUC1, a cell membrane-spanning mucin was immunohistologically confirmed in the HCE models after exposing not only eye irritant chemicals but also false-positive chemicals, suggesting that such false-positive chemicals have an eye irritant potential. These data demonstrated that the Vitrigel-EIT method could provide excellent predictive performance to judge the widespread eye irritancy, including very mild irritant chemicals. We hope that the Vitrigel-EIT method contributes to the development of safe commodity chemicals. Copyright © 2015 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd. PMID:26472347

  19. Development of an in vitro alternative assay method for vaginal irritation.

    PubMed

    Ayehunie, Seyoum; Cannon, Chris; Larosa, Karen; Pudney, Jeffrey; Anderson, Deborah J; Klausner, Mitchell

    2011-01-11

    The vaginal mucosa is commonly exposed to chemicals and therapeutic agents that may result in irritation and/or inflammation. In addition to acute effects, vaginal irritation and inflammation can make women more susceptible to infections such as HIV-1 and herpes simplex virus 2 (HSV-2). Hence, the vaginal irritation potential of feminine care formulations and vaginally administered therapeutic agents is a significant public health concern. Traditionally, testing of such materials has been performed using the rabbit vaginal irritation (RVI) assay. In the current study, we investigated whether the organotypic, highly differentiated EpiVaginal™ tissue could be used as a non-animal alternative to the RVI test. The EpiVaginal tissue was exposed to a single application of ingredients commonly found in feminine hygiene products and the effects on tissue viability (MTT assay), barrier disruption (measured by transepithelial electrical resistance, TEER and sodium fluorescein (NaFl) leakage), and inflammatory cytokine release (interleukin (IL)-1α, IL-1β, IL-6, and IL-8) patterns were examined. When compared to untreated controls, two irritating ingredients, nonoxynol 9 and benzalkonium chloride, reduced tissue viability to <40% and TEER to <60% while increasing NaFl leakage by 11-24% and IL-1α and IL-1β release by >100%. Four other non-irritating materials had minimal effects on these parameters. Assay reproducibility was confirmed by testing the chemicals using three different tissue production lots and by using tissues reconstructed from cells obtained from three different donors. Coefficients of variation between tissue lots reconstructed with cells obtained from the same donor or lots reconstructed with cells obtained from different donors were less than 10% and 12%, respectively. In conclusion, decreases in tissue viability and barrier function and increases in IL-1α and IL-1β release appear to be useful endpoints for preclinical screening of topically applied

  20. Evaluation of dermal and eye irritation and skin sensitization due to carbon nanotubes.

    PubMed

    Ema, Makoto; Matsuda, Akitaka; Kobayashi, Norihiro; Naya, Masato; Nakanishi, Junko

    2011-12-01

    The present paper summarizes the results of our studies on dermal and eye irritation and skin sensitization due to carbon nanotubes (CNTs), whose potential applications and uses are wide and varied, including CNT-enhanced plastics, electromagnetic interference/radio-frequency (EMI/RFI) shielding, antistatic material, flexible fibers and advanced polymers, medical and health applications, and scanning probe microscopy. Skin and eyes have the highest risk of exposure to nanomaterials, because deposition of nanomaterials to the surficial organs has the potential to be a major route of exposure during the manufacturing, use, and disposal of nanomaterials. Two products composed of single-walled carbon nanotubes (SWCNTs) and two products composed of multi-walled carbon nanotubes (MWCNTs) were tested regarding acute dermal and acute eye irritation using rabbits, and skin sensitization using guinea pigs. The concentrations of the CNTs in the substances were the maximum allowable for administration. The two products of SWCNTs and one of the products of MWCNTs were not irritants to the skin or eyes. The other product of MWCNTs caused very slight erythema at 24h, but not at 72h, after patch removal in the dermal irritation experiments and conjunctival redness and blood vessel hyperemia at 1h, but not at 24h, in eye irritation experiments. These findings showed that one product of MWCNTs was a very weak acute irritant to the skin and eyes. No products of SWCNTs and MWCNTs exhibited skin-sensitization effects. Our knowledge of the toxicological effects of CNTs is still limited. Further information is needed to clarify the potential for irritation and sensitization given the complex nature of CNTs. PMID:21893152

  1. Characterization of new eye drops with choline salicylate and assessment of their irritancy by in vitro short time exposure tests.

    PubMed

    Wroblewska, Katarzyna; Kucinska, Małgorzata; Murias, Marek; Lulek, Janina

    2015-09-01

    The aim of our study was to examine the irritation potential of new eye drops containing 2% choline salicylate (CS) as an active pharmaceutical ingredient (API) and various polymers increasing eye drop viscosity (hydroxyethylcellulose, hydroxypropyl methylcellulose, methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone). The standard method for assessing the potential of irritating substances has been the Draize rabbit eye test. However the European Centre for Validation of Alternative Methods and the Coordinating Committee for Validation of Alternative Methods recommend, short time exposure (STE) in vitro tests as an alternative method for assessing eye irritation. The eye irritation potential was determined using cytotoxicity test methods for rabbit corneal cell line (SIRC) after 5 min exposure. The viability of cells was determined using two cytotoxicity assays: MTT and Neutral Red Uptake. According to the irritation rankings for the short time exposure test, all tested eye drops are classified as non-irritating (cell viability >70%). PMID:27134543

  2. Characterization of new eye drops with choline salicylate and assessment of their irritancy by in vitro short time exposure tests

    PubMed Central

    Wroblewska, Katarzyna; Kucinska, Małgorzata; Murias, Marek; Lulek, Janina

    2014-01-01

    The aim of our study was to examine the irritation potential of new eye drops containing 2% choline salicylate (CS) as an active pharmaceutical ingredient (API) and various polymers increasing eye drop viscosity (hydroxyethylcellulose, hydroxypropyl methylcellulose, methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone). The standard method for assessing the potential of irritating substances has been the Draize rabbit eye test. However the European Centre for Validation of Alternative Methods and the Coordinating Committee for Validation of Alternative Methods recommend, short time exposure (STE) in vitro tests as an alternative method for assessing eye irritation. The eye irritation potential was determined using cytotoxicity test methods for rabbit corneal cell line (SIRC) after 5 min exposure. The viability of cells was determined using two cytotoxicity assays: MTT and Neutral Red Uptake. According to the irritation rankings for the short time exposure test, all tested eye drops are classified as non-irritating (cell viability >70%). PMID:27134543

  3. Alcohol Use Disorder Increases the Risk of Irritable Bowel Disease

    PubMed Central

    Hsu, Tai-Yi; He, Guan-Yi; Wang, Yu-Chiao; Chen, Chih-Yu; Wang, Shih-Hao; Chen, Wei-Kung; Kao, Chia-Hung

    2015-01-01

    Abstract Alcohol use disorder (AUD) is considered a possible risk factor for irritable bowel syndrome (IBS); however, previous studies investigating the association between AUD and IBS have yielded inconsistent results. The study investigated whether AUD increases the risk of IBS by using a population-based database in Taiwan. This retrospective matched-cohort study included the health insurance claims data of 56,355 AUD inpatients and 225,420 randomly selected controls by frequency-matched for sex, age, and index year. Cox proportional hazards regression analysis was performed to measure the risk of IBS among AUD patients compared with non-AUD patients. During the follow-up period, the incidence rate ratio (IRR) of IBS had 12.3-fold (95% CI: 11.9–12.7) in the AUD patients than non-AUD patients and the adjusted hazard ratio (aHR) for IBS in the AUD patients was 5.51 (95% CI: 4.36–6.96). For several comorbidities, the risk of IBS was significantly higher in the AUD patients than in non-AUD patients, with aHRs of 2.14 (95% confidence interval [CI]: 1.19–3.84), 2.05 (95% CI: 1.06–3.96), and 2.91 (95% CI: 1.26–6.72) for sleep disorders, acute pancreatitis, and hepatitis B, respectively. When we stratified the severity of AUD according to the length of hospital stay, the aHRs exhibited a significant correlation (P < 0.001) with severity, yielding aHRs of 3.24 (95% CI: 2.49–4.22), 11.9 (95% CI: 8.96–15.9), and 26.1 (95% CI: 19.4–35.2) for mild, moderate, and severe AUD, respectively. The risk of IBS was higher among AUD patients, and increased with the length of hospital stay. PMID:26705226

  4. Irritable Bowel Syndrome Increases the Risk of Epilepsy

    PubMed Central

    Chen, Chien-Hua; Lin, Cheng-Li; Kao, Chia-Hung

    2015-01-01

    Abstract An abnormal interaction in the brain–gut axis is regarded as the cause of irritable bowel syndrome (IBS). We attempted to determine the association between IBS and subsequent development of epilepsy. A total of 32,122 patients diagnosed with IBS between 2000 and 2011 were identified from the Longitudinal Health Insurance Database as the study cohort, and 63,295 controls were randomly selected from the insurants without IBS and frequency-matched according to age, sex, and index year as the comparison cohort. Both cohorts were followed up until the end of 2011 to measure the incidence of epilepsy. We analyzed the risks of epilepsy using Cox proportional hazards regression models. The IBS patients had greater cumulative incidence of epilepsy than the cohort without IBS (log-rank test, P < 0.001 and 2.54 versus 1.86 per 1000 person-years). The IBS cohort had a higher risk of epilepsy after adjusting for age, sex, diabetes, hypertension, stroke, coronary artery disease, head injury, depression, systemic lupus erythematosus, brain tumor, and antidepressants usage (adjusted hazard ratio [aHR]: 1.30, 95% confidence interval [CI]: 1.17–1.45). Stratified by the presence of other risk factors, the relative risk was also greater for patients with (aHR: 1.25, 95% CI: 1.10–1.41) or without other risk factors (aHR: 1.68, 95% CI: 1.35–2.10) in the IBS cohort than for those in the non-IBS cohort. The age-specific relative risk of epilepsy in the IBS cohort was greater than that in the non-IBS cohort for both 35 to 49 age group and 50 to 64 age group (age ≤ 34, aHR:1.31, 95% CI: 0.93–1.85; age 35–49, aHR: 1.43, 95% CI: 1.12–1.83; age 50–64, aHR: 1.56, 95% CI: 1.27–1.91). However, there was no difference between patients > 65 years with IBS and those without IBS (aHR: 1.11, 95% CI: 0.94–1.31). This population-based cohort study revealed that IBS increases the risk of developing epilepsy. However, IBS may be less influential than other risk factors

  5. Personality factors and profiles in variants of irritable bowel syndrome

    PubMed Central

    Farnam, Alireza; Somi, Mohammad H; Sarami, Firouz; Farhang, Sara; Yasrebinia, Sanaz

    2007-01-01

    AIM: To study the association between irritable bowel syndrome (IBS) variants (constipation, diarrhea, or both) and personality traits in non-psychiatric patients. METHODS: IBS was diagnosed using the Rome II diagnostic criteria after exclusion of organic bowel pathology. The entry of each patient was confirmed following a psychiatric interview. Personality traits and the score of each factor were evaluated using the NEO Five Factor Inventory. RESULTS: One hundred and fifty patients were studied. The mean age (± SD) was 33.4 (± 11.0) year (62% female). Subjects scored higher in neuroticism (26.25 ± 7.80 vs 22.92 ± 9.54, P < 0.0005), openness (26.25 ± 5.22 vs 27.94 ± 4.87, P < 0.0005) and conscientiousness (32.90 ± 7.80 vs 31.62 ± 5.64, P < 0.01) compared to our general population derived from universities of Iran. Our studied population consisted of 71 patients with Diarrhea dominant-IBS, 33 with Constipation dominant-IBS and 46 with Altering type-IBS. Scores of conscientiousness and neuroticism were significantly higher in C-IBS compared to D-IBS and A-IBS (35.79 ± 5.65 vs 31.95 ± 6.80, P = 0.035 and 31.97 ± 9.87, P = 0.043, respectively). Conscientiousness was the highest dimension of personality in each of the variants. Patients with C-IBS had almost similar personality profiles, composed of higher scores for neuroticism and conscientiousness, with low levels of agreeableness, openness and extraversion that were close to those of the general population. CONCLUSION: Differences were observed between IBS patients and the general population, as well as between IBS subtypes, in terms of personality factors. Patients with constipation-predominant IBS showed similar personality profiles. Patients with each subtype of IBS may benefit from psychological interventions, which can be focused considering the characteristics of each subtype. PMID:18081232

  6. Effect of São Pedro do Sul thermal water on skin irritation.

    PubMed

    Ferreira, M O; Costa, P C; Bahia, M F

    2010-06-01

    Many mineral waters are known for centuries for treating dermatological diseases but there is little scientific evaluation of the effects of these waters in skin. A total of 17 healthy Caucasian volunteers, including men and women, were enrolled in this study. Two skin sites were marked on each volunteer forearm and irritated with sodium lauryl sulphate at 2% (w/v) kept under occlusion for 24 h with Finn chambers. Afterwards, purified water or São Pedro do Sul (SPS) thermal water were applied to the irritated skin sites, and kept under occlusion for 48 h also with Finn chambers. Transepidermal water loss (TEWL) was used as a measure of the skin barrier function to evaluate the potential anti-irritant effect of the thermal water on skin. Statistically significant differences in the mean TEWL variations were observed for the skin treated with SPS thermal water and with purified water (P = 0.036). The thermal water reduced the degree to which the skin barrier was disrupted compared with purified water alone in 82.4% of the volunteers. The SPS thermal water is anti-irritant and, therefore, can be helpful to relieve skin irritation and in cosmetic formulations to improve the tolerability of the products. PMID:20557578

  7. Influence of temperature on irritation in the hand/forearm immersion test.

    PubMed

    Clarys, P; Manou, I; Barel, A O

    1997-05-01

    As indicated by in vitro experiments the penetration of irritants through the skin is significantly influenced by the temperature of the solution. In vivo experiments, demonstrated equally a significant influence of temperature in surfactant-induced skin irritation. In order to evaluate the irritant potential of detergent solutions under normal user conditions, we used the hand/forearm immersion test. We compared 2 detergents with different anionic character in a repetitive immersion protocol (30 min immersion on 4 consecutive days). The solutions were tested at 2 temperatures (37 degrees C and 40 degrees C). The irritation was quantified by assessment of the stratum corneum barrier function (transepidermal water loss), skin redness (a* colour parameter) and skin dryness (capacitance method). Both detergents affected the integrity of the skin in a significant way. The anionic content as well as the temperature of the solutions were found to be determinative for the irritant potential, with a stronger response for higher anionic content and temperature, respectively. PMID:9197957

  8. Association of MHC region SNPs with irritant susceptibility in healthcare workers.

    PubMed

    Yucesoy, Berran; Talzhanov, Yerkebulan; Michael Barmada, M; Johnson, Victor J; Kashon, Michael L; Baron, Elma; Wilson, Nevin W; Frye, Bonnie; Wang, Wei; Fluharty, Kara; Gharib, Rola; Meade, Jean; Germolec, Dori; Luster, Michael I; Nedorost, Susan

    2016-09-01

    Irritant contact dermatitis is the most common work-related skin disease, especially affecting workers in "wet-work" occupations. This study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) within the major histocompatibility complex (MHC) and skin irritant response in a group of healthcare workers. 585 volunteer healthcare workers were genotyped for MHC SNPs and patch tested with three different irritants: sodium lauryl sulfate (SLS), sodium hydroxide (NaOH) and benzalkonium chloride (BKC). Genotyping was performed using Illumina Goldengate MHC panels. A number of SNPs within the MHC Class I (OR2B3, TRIM31, TRIM10, TRIM40 and IER3), Class II (HLA-DPA1, HLA-DPB1) and Class III (C2) genes were associated (p < 0.001) with skin response to tested irritants in different genetic models. Linkage disequilibrium patterns and functional annotations identified two SNPs in the TRIM40 (rs1573298) and HLA-DPB1 (rs9277554) genes, with a potential impact on gene regulation. In addition, SNPs in PSMB9 (rs10046277 and ITPR3 (rs499384) were associated with hand dermatitis. The results are of interest as they demonstrate that genetic variations in inflammation-related genes within the MHC can influence chemical-induced skin irritation and may explain the connection between inflamed skin and propensity to subsequent allergic contact sensitization. PMID:27258892

  9. Evaluation of acute skin irritation and phototoxicity by aqueous and ethanol fractions of Angelica keiskei

    PubMed Central

    LEE, SANG-HAN

    2013-01-01

    In this study, to assess whether aqueous and ethanol fractions of Angelica keiskei induce acute skin irritation and phototoxicity, acute skin irritancy and phototoxicity tests were performed. The skin of rabbits or guinea pigs was treated with these fractions (100 mg/dose) and whether the animals sustained significant skin damage was determined. The data demonstrated that the aqueous and ethanol fractions of Angelica keiskei did not induce acute toxicity in the skin of the animals, as assessed by anatomical and pathological observations. The results from the present study suggest that these aqueous and ethanol fractions of Angelica keiskei have promising potential uses as cosmetic ingredients that do not induce significant levels of skin irritation or phototoxicity. PMID:23251240

  10. Irritable Bowel Syndrome and the Small Intestinal Microflora. What Do We Know?

    PubMed

    Moraru, Ioana G; Moraru, A G; Dumitraşcu, D L

    2015-01-01

    Irritable bowel syndrome, one of the most common functional gastro intestinal disorders all over the world is considered to have a multi factorial pathogenesis. Recently more and more studies are focusing on the changes that take place in the microbiota of patients with irritable bowel syndrome, underlining the bacterial role in this pathogenesis. As a consequence, bacterial overgrowth, along with intestinal dysmotility, altered brain-gut axis and genetic factors are considered part of this pathophysiology. This report intends to summarize the actual knowledge on irritable bowel syndrome and small intestinal bacterial overgrowth syndrome, from details on the epidemiology, clinical manifestation, pathophysiology, diagnosis, treatment to details on the relationship between these two syndromes. PMID:26076568

  11. Towards an Irritable Bowel Syndrome Control System Based on Artificial Neural Networks

    NASA Astrophysics Data System (ADS)

    Podolski, Ina; Rettberg, Achim

    To solve health problems with medical applications that use complex algorithms is a trend nowadays. It could also be a chance to help patients with critical problems caused from nerve irritations to overcome them and provide a better living situation. In this paper a system for monitoring and controlling the nerves from the intestine is described on a theoretical basis. The presented system could be applied to the irritable bowel syndrome. For control a neural network is used. The advantages for using a neural network for the control of irritable bowel syndrome are the adaptation and learning. These two aspects are important because the syndrome behavior varies from patient to patient and have also concerning the time a lot of variations with respect to each patient. The developed neural network is implemented and can be simulated. Therefore, it can be shown how the network monitor and control the nerves for individual input parameters.

  12. Removal of an Extra-large Irritation Fibroma With a Combination of Diode Laser and Scalpel

    PubMed Central

    Bakhtiari, Sedigheh; Taheri, Jamileh Bigom; Sehhatpour, Marziye; Asnaashari, Mohammad; Attarbashi Moghadam, Saaedeh

    2015-01-01

    Introduction: Irritation fibroma is the most common tumor like and sub mucosal reactive lesion in the oral cavity. Usually it is measured less than 1.5 cm in diameter; however in rare case it has more than 3 cm in diameter. Different kind of treatment for soft tissue lesions include scalpel excision, electrical surgery, and laser surgery. The diode laser can be more effective than conventional surgery, electrosurgery and cryosurgery in reduction of bleeding and pain. Case Report: We reported a very large irritation fibroma in right lingual side of retromolar pad which was less prone to be traumatized under local irritation, in a woman wearing maxillary complete denture and use of both diode laser and scalpel for its excision. PMID:26705465

  13. Role of protective gloves in the causation and treatment of occupational irritant contact dermatitis.

    PubMed

    Kwon, Soonyou; Campbell, Lauren S; Zirwas, Matthew J

    2006-11-01

    Irritant contact dermatitis of the hands is a significant occupational problem. Management primarily involves cessation of exposure to hazardous substances. Protective gloves can reduce or eliminate exposure of the hands to hazardous substances if used correctly, but if not selected and used correctly, protective gloves can actually cause or worsen irritant contact dermatitis of the hands by increasing exposure of the hands to hazardous chemicals. We present two cases of occupational irritant contact dermatitis of the hands caused by incorrect use of protective gloves. Glove failure can occur by penetration, permeation, or contamination, and all 3 mechanisms were operative in these cases. These cases demonstrate that correct use of gloves is at least as important as selection of gloves made of the appropriate material. By understanding mechanisms of glove failure, clinicians can make more appropriate recommendations for the selection and use of protective gloves in the workplace. PMID:17052501

  14. Identifying an indoor air exposure limit for formaldehyde considering both irritation and cancer hazards

    PubMed Central

    Golden, Robert

    2011-01-01

    Formaldehyde is a well-studied chemical and effects from inhalation exposures have been extensively characterized in numerous controlled studies with human volunteers, including asthmatics and other sensitive individuals, which provide a rich database on exposure concentrations that can reliably produce the symptoms of sensory irritation. Although individuals can differ in their sensitivity to odor and eye irritation, the majority of authoritative reviews of the formaldehyde literature have concluded that an air concentration of 0.3 ppm will provide protection from eye irritation for virtually everyone. A weight of evidence-based formaldehyde exposure limit of 0.1 ppm (100 ppb) is recommended as an indoor air level for all individuals for odor detection and sensory irritation. It has recently been suggested by the International Agency for Research on Cancer (IARC), the National Toxicology Program (NTP), and the US Environmental Protection Agency (US EPA) that formaldehyde is causally associated with nasopharyngeal cancer (NPC) and leukemia. This has led US EPA to conclude that irritation is not the most sensitive toxic endpoint and that carcinogenicity should dictate how to establish exposure limits for formaldehyde. In this review, a number of lines of reasoning and substantial scientific evidence are described and discussed, which leads to a conclusion that neither point of contact nor systemic effects of any type, including NPC or leukemia, are causally associated with exposure to formaldehyde. This conclusion supports the view that the equivocal epidemiology studies that suggest otherwise are almost certainly flawed by identified or yet to be unidentified confounding variables. Thus, this assessment concludes that a formaldehyde indoor air limit of 0.1 ppm should protect even particularly susceptible individuals from both irritation effects and any potential cancer hazard. PMID:21635194

  15. Irritancy and allergic responses induced by topical application of ortho-phthalaldehyde.

    PubMed

    Anderson, Stacey E; Umbright, Christina; Sellamuthu, Rajendran; Fluharty, Kara; Kashon, Michael; Franko, Jennifer; Jackson, Laurel G; Johnson, Victor J; Joseph, Pius

    2010-06-01

    Although ortho-phthalaldehyde (OPA) has been suggested as an alternative to glutaraldehyde for the sterilization and disinfection of hospital equipment, the toxicity has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of OPA. The EpiDerm Skin Irritation Test was used to evaluate in vitro irritancy potential of OPA and glutaraldehyde. Treatment with 0.4125 and 0.55% OPA induced irritation, while glutaraldehyde exposure at these concentrations did not. Consistent with the in vitro results, OPA induced irritancy, evaluated by ear swelling, when mice were treated with 0.75%. Initial evaluation of the sensitization potential was conducted using the local lymph node assay at concentrations ranging from 0.005 to 0.75%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.051% compared to that of 0.089%, previously determined for glutaraldehyde. Immunoglobulin (Ig) E-inducing potential was evaluated by phenotypic analysis of draining lymph node (DLN) cells and measurement of total and specific serum IgE levels. The 0.1 and 0.75% exposed groups yielded significant increases in the IgE+B220+ cell population in the lymph nodes while the 0.75% treated group demonstrated significant increases in total IgE, OPA-specific IgE, and OPA-specific IgG(1). In addition, significant increases in interleukin-4 messenger RNA and protein expression in the DLNs were observed in OPA-treated groups. The results demonstrate the dermal irritancy and allergic potential of OPA and raise concern about the proposed/intended use of OPA as a safe alternative to glutaraldehyde. PMID:20176622

  16. Review of skin irritation/corrosion Hazards on the basis of human data: A regulatory perspective

    PubMed Central

    Jírova, Dagmar; Kandárová, Helena

    2012-01-01

    Regulatory classification of skin irritation has historically been based on rabbit data, however current toxicology processes are transitioning to in vitro alternatives. The in vitro assays have to provide sufficient level of sensitivity as well as specificity to be accepted as replacement methods for the existing in vivo assays. This is usually achieved by comparing the in vitro results to classifications obtained in animals. Significant drawback of this approach is that neither in vivo nor in vitro methods are calibrated against human hazard data and results obtained in these assays may not correspond to situation in human. The main objective of this review was to establish an extended database of substances classified according to their human hazard to serve for further development of alternative methods relevant to human health as well as resource for improved regulatory classification. The literature has been reviewed to assemble all the available information on the testing of substances in the human 4 h human patch test, which is the only standardized protocol in humans matching the exposure conditions of the regulatory accepted in vivo rabbit skin irritation test. A total of 81 substances tested according to the defined 4 h human patch test protocol were found and collated into a dataset together with their existing in vivo classifications published in the literature. While about 50% of the substances in the database are classified as irritating based on the rabbit skin test, on using the 4 h HPT test, less than 20% were identified as acutely irritant to human skin. Based on the presented data, it can be concluded that the rabbit skin irritation test largely over-predicts human responses for the evaluated chemicals. Correct classification of the acute skin irritation hazard will only be possible if newly developed in vitro toxicology methods will be calibrated to produce results relevant to man. PMID:23118595

  17. IL-6 deficiency exacerbates skin inflammation in a murine model of irritant dermatitis.

    PubMed

    Lee, Eric G; Mickle-Kawar, Bethany M; Gallucci, Randle M

    2013-01-01

    Contact dermatitis is the second most reported occupational injury associated with workers compensation. Inflammatory cytokines are closely involved with the development of dermatitis, and their modulation could exacerbate skin damage, thus contributing to increased irritancy. IL-6 is a pro-inflammatory cytokine paradoxically associated with both skin healing and inflammation. To determine what role this pleiotropic cytokine plays in chemically-induced irritant dermatitis, IL-6 deficient (KO), IL-6 over-expressing transgenic (TgIL6), and corresponding wild-type (WT) mice were exposed to acetone or the irritants JP-8 jet fuel or benzalkonium chloride (BKC) daily for 7 days. Histological analysis of exposed skin was performed, as was tissue mRNA and protein expression patterns of inflammatory cytokines via QPCR and multiplex ELISA. The results indicated that, following JP-8 exposure, IL-6KO mice had greatly increased skin IL-1β, TNFα, CCL2, CCL3, and CXCL1 mRNA and corresponding product protein expression when compared to that of samples from WT counterparts and acetone-exposed control mice. BKC treatment induced the expression of all cytokines examined as compared to acetone, with CCL2 significantly higher in skin from IL-6KO mice. Histological analysis showed that IL-6KO mice displayed significantly more inflammatory cell infiltration as compared to WT and TgIL6 mice in response to jet fuel. Analysis of mRNA for the M2 macrophage marker CD206 indicated a 4-fold decrease in skin of IL-6KO mice treated with either irritant as compared to WT. Taken together, these observations suggest that IL-6 acts in an anti-inflammatory manner during irritant dermatitis, and these effects are dependent on the chemical nature of the irritant. PMID:22966985

  18. Encapsulation of Mentha Oil in Chitosan Polymer Matrix Alleviates Skin Irritation.

    PubMed

    Mishra, Nidhi; Rai, Vineet Kumar; Yadav, Kuldeep Singh; Sinha, Priyam; Kanaujia, Archana; Chanda, Debabrata; Jakhmola, Apurva; Saikia, Dharmendra; Yadav, Narayan Prasad

    2016-04-01

    Mentha spicata L. var. viridis oil (MVO) is a potent antifungal agent, but its application in the topical treatment is limited due to its irritancy and volatility. It was aimed to develop more efficient, chitosan-incrusted MVO microspheres with reduced volatility and lesser irritancy and to dispense it in the form of ointment. Simple coacervation technique was employed to microencapsulate MVO in chitosan matrix. Morphological properties and polymer cross-linking were characterized by scanning electron microscopy and differential scanning calorimetry, respectively. Optimization was carried out on the basis of entrapment efficiency (EE) using response surface methodology. Well-designed microspheres having smooth surface and spherical shape were observed. EE (81.20%) of optimum batch (R21) was found at 1.62% w/v of cross-linker, 5.4:5 of MVO to chitosan ratio and at 1000 rpm. R21 showed 69.38 ± 1.29% in vitro MVO release in 12 h and 96.92% retention of MVO in microspheres even after 8 week. Ointments of PEG 4000 and PEG 400 comprising MVO (F1) and R21 (F2) were developed separately. F2 showed comparatively broader zone of growth inhibition (13.33 ± 1.76-18.67 ± 0.88 mm) and less irritancy (PII 0.5833, irritation barely perceptible) than that of F1. F2 was able to avoid the direct contact of mild irritant MVO with the skin and to reduce its rapid volatility. Controlled release of MVO helped in lengthening the duration of availability of MVO in agar media and hence improved its therapeutic efficacy. In conclusion, a stable and non-irritant formulation with improved therapeutic potential was developed. PMID:26248538

  19. Comparison of in vitro cell toxicity with in vivo eye irritation.

    PubMed

    Bracher, M; Faller, C; Spengler, J; Reinhardt, C A

    The effects of 26 different cosmetic ingredients (e.g., permanent wave and hair dye compounds, emulsifiers, resins, and detergents such as quats) were assessed by four end points indicative for qualitatively and quantitatively different cytotoxicity: (1) neutral red uptake reduction after 24 h of treatment (NR-90 and NR-50); (2) cell detachment from culture dish after 4 h of treatment (CD-25); (3) growth inhibition after 48 h of treatment (GI-50); and (4) membrane permeability measured by fluorescent dye retention (fluorescence shift FS-25) and dye exclusion (viability ratio VR-25). The cytotoxicity potentials of the test agents were ranked for each in vitro test and compared with the in vivo eye irritation in guinea pigs (Draize test) after application of 5 or 2.5% (w/v) solutions of the same test batches. Strong irritants could be easily detected by most of the in vitro tests, but the neutral red uptake assay (especially NR-50) was the only one that was able to distinguish the minimally irritating test agents from strong irritants as well as from nonirritants. (I) All three extremely irritating quaternary ammonia compounds were identified as the strongest cytotoxic agents. (II) Nine out of 12 minimally irritating substances (mainly emulsifiers and resins) were ranked in the intermediate group. (III) Eight out of 11 non-or practically nonirritating chemicals (mainly permanent wave compounds) showed cytotoxic effects at very high concentrations only. The distinction of these three groups was better by means of NR-50 than by NR-90 data. At least two of the other cell tests (CD-25, GI-50, FS-25, and VR-25) had to be considered to allow an adequate interpretation of in vitro cytotoxicity. PMID:3509702

  20. Evaluation of Eye Irritation Potential of Solid Substance with New 3D Reconstructed Human Cornea Model, MCTT HCETM

    PubMed Central

    Jang, Won-hee; Jung, Kyoung-mi; Yang, Hye-ri; Lee, Miri; Jung, Haeng-Sun; Lee, Su-Hyon; Park, Miyoung; Lim, Kyung-Min

    2015-01-01

    The eye irritation potential of drug candidates or pharmaceutical ingredients should be evaluated if there is a possibility of ocular exposure. Traditionally, the ocular irritation has been evaluated by the rabbit Draize test. However, rabbit eyes are more sensitive to irritants than human eyes, therefore substantial level of false positives are unavoidable. To resolve this species difference, several three-dimensional human corneal epithelial (HCE) models have been developed as alternative eye irritation test methods. Recently, we introduced a new HCE model, MCTT HCETM which is reconstructed with non-transformed human corneal cells from limbal tissues. Here, we examined if MCTT HCETM can be employed to evaluate eye irritation potential of solid substances. Through optimization of washing method and exposure time, treatment time was established as 10 min and washing procedure was set up as 4 times of washing with 10 mL of PBS and shaking in 30 mL of PBS in a beaker. With the established eye irritation test protocol, 11 solid substances (5 non-irritants, 6 irritants) were evaluated which demonstrated an excellent predictive capacity (100% accuracy, 100% specificity and 100% sensitivity). We also compared the performance of our test method with rabbit Draize test results and in vitro cytotoxicity test with 2D human corneal epithelial cell lines. PMID:26157556

  1. Irritability Levels of Field and Laboratory Population of Culex pipiens Complex in Tehran to Different Groups of Insecticides

    PubMed Central

    Rahimi, Sara; Vatandoost, Hassan; Abai, Mohammad Reza; Raeisi, Ahmad; Hanafi-Bojd, Ahmad Ali; Rafi, Fatemeh

    2016-01-01

    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. PMID:27308276

  2. Slight respiratory irritation but not inflammation in mice exposed to (1-->3)-beta-D-glucan aerosols.

    PubMed Central

    Korpi, A; Kasanen, J-P; Kosma, V-M; Rylander, R; Pasanen, A-L

    2003-01-01

    Airway irritation effects after single and repeated inhalation exposures to aerosols of beta-glucan (grifolan) were investigated in mice. In addition, the effects on serum total immunoglobulin E (IgE) production and histopathological inflammation in the respiratory tract were studied. The beta-glucan aerosols provoked slight sensory irritation in the airways, but the response was not concentration dependent at the levels studied. Slight pulmonary irritation was observed after repeated exposures. No effect was found on the serum total IgE levels, and no signs of inflammation were seen in the airways 6 h after the final exposure. The results suggest that, irrespective of previous fungal sensitization of the animals, inhaled beta-glucan may cause symptoms of respiratory tract irritation but without apparent inflammation. Respiratory tract irritation reported after inhalation of fungi may not be entirely attributed to beta-glucan. PMID:12857597

  3. Deconstructing Oppositional Defiant Disorder: Clinic-Based Evidence for an Anger/Irritability Phenotype

    ERIC Educational Resources Information Center

    Drabick, Deborah A. G.; Gadow, Kenneth D.

    2012-01-01

    Objective: To examine risk factors and co-occurring symptoms associated with mother-reported versus teacher-reported anger/irritability symptoms (AIS) of oppositional defiant disorder (ODD) in a clinic-based sample of 1,160 youth aged 6 through 18 years. Method: Participants completed a background history questionnaire (mothers), school…

  4. Anger and Irritability Symptoms among Youth with ODD: Cross-Informant versus Source-Exclusive Syndromes

    ERIC Educational Resources Information Center

    Gadow, Kenneth D.; Drabick, Deborah A. G.

    2012-01-01

    We examined differences in co-occurring psychological symptoms and background characteristics among clinically referred youth with oppositional defiant disorder (ODD) with and without anger/irritability symptoms (AIS) according to either parent or teacher (source-exclusive) and both informants (cross-informant), youth with noncompliant symptoms…

  5. Anxiety, Depression, and Irritability in Children with Autism Relative to Other Neuropsychiatric Disorders and Typical Development

    ERIC Educational Resources Information Center

    Mayes, Susan Dickerson; Calhoun, Susan L.; Murray, Michael J.; Ahuja, Meesha; Smith, Laura A.

    2011-01-01

    Maternal ratings of anxiety, depression, and irritability were analyzed in 1390 children (6-16 years of age), including 233 children with high functioning autism (HFA, IQ greater than or equal to 80), 117 children with low functioning autism (LFA, IQ less than 80), 187 typical children, and 853 children with other disorders. As a group, children…

  6. Subtypes of irritable bowel syndrome based on abdominal pain/discomfort severity and bowel pattern

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Irritable bowel syndrome (IBS) has traditionally been classified by stooling pattern (e.g., diarrhea-predominant). However, other patterns of symptoms have long been recognized, e.g., pain severity. Our objective was to examine the utility of subtyping women with IBS based on pain/discomfort severit...

  7. Psychological Treatments for Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis

    ERIC Educational Resources Information Center

    Lackner, Jeffrey M.; Mesmer, Christina; Morley, Stephen; Dowzer, Clare; Hamilton, Simon

    2004-01-01

    This study conducted a systematic review to assess the quality of existing literature on psychological treatments for irritable bowel syndrome and to quantify the evidence for their efficacy. Three independent reviewers (2 from England, 1 from the United States) coded the quality of 32 studies, 17 of which provided data suitable for meta-analysis.…

  8. Type A Behavior and Marital Satisfaction: Differential Effects of Achievement Striving and Impatience/Irritability.

    ERIC Educational Resources Information Center

    MacEwen, Karyl; Barling, Julian

    1993-01-01

    Examined how dimensions of Type A behavior exert different effects on marital relationship. Findings from 200 couples are consistent with view that Type A behavior should be divided into at least 2 components, and that it is Impatience/Irritability dimension rather than achievement-oriented or job-involved dimension that exerts detrimental effects…

  9. [Irritable bowel syndrome in the light of Rome consensus III (2006): 10 years later].

    PubMed

    Parfenov, A I; Albulova, E A; Ruchkina, I N

    2016-01-01

    Irritable bowel syndrome (IBS) is the most common diagnosis in gastroenterology. Over 10 years after Rome consensus III (2006), there has been much new information on the pathogenesis of IBS and its therapy options. The paper analyzes basic investigations that have contributed to the theory of this disease and to a better quality of life in patients. PMID:27135104

  10. Daily Shame and Hostile Irritability in Adolescent Girls with Borderline Personality Disorder Symptoms

    PubMed Central

    Scott, Lori N.; Stepp, Stephanie D.; Hallquist, Michael N.; Whalen, Diana J.; Wright, Aidan G. C.; Pilkonis, Paul A.

    2014-01-01

    Recent theoretical and empirical work suggests that adults with borderline personality disorder (BPD) have difficulty regulating both shame and anger, and that these emotions may be functionally related in clinically relevant ways (e.g., Schoenleber & Berenbaum, 2012b). The covariation of shame with anger-related emotions has important clinical implications for interventions targeting shame and uncontrolled anger in BPD. However, no studies have examined shame, anger, and their covariation in adolescents who may be at risk for developing BPD. Therefore, this study focuses on associations between BPD symptoms and patterns of covariation between daily experiences of shame and anger-related affects (i.e., hostile irritability) in a community sample of adolescent girls using ecological momentary assessment. Multilevel models revealed that girls with greater BPD symptoms who reported greater mean levels of shame across the week also tended to report more hostile irritability, even after controlling for guilt. Additionally, examination of within-person variability showed that girls with greater BPD symptoms reported more hostile irritability on occasions when they also reported greater concurrent shame, but this was only the case in girls of average socioeconomic status (i.e., those not receiving public assistance). Unlike shame, guilt was not associated with hostile irritability in girls with greater BPD symptoms. Results suggest that shame may be a key clinical target in the treatment of anger-related difficulties among adolescent girls with BPD symptoms. PMID:25580673

  11. Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals

    PubMed Central

    Tizzano, Marco; Gulbransen, Brian D.; Vandenbeuch, Aurelie; Clapp, Tod R.; Herman, Jake P.; Sibhatu, Hiruy M.; Churchill, Mair E. A.; Silver, Wayne L.; Kinnamon, Sue C.; Finger, Thomas E.

    2010-01-01

    The upper respiratory tract is continually assaulted with harmful dusts and xenobiotics carried on the incoming airstream. Detection of such irritants by the trigeminal nerve evokes protective reflexes, including sneezing, apnea, and local neurogenic inflammation of the mucosa. Although free intra-epithelial nerve endings can detect certain lipophilic irritants (e.g., mints, ammonia), the epithelium also houses a population of trigeminally innervated solitary chemosensory cells (SCCs) that express T2R bitter taste receptors along with their downstream signaling components. These SCCs have been postulated to enhance the chemoresponsive capabilities of the trigeminal irritant-detection system. Here we show that transduction by the intranasal solitary chemosensory cells is necessary to evoke trigeminally mediated reflex reactions to some irritants including acyl–homoserine lactone bacterial quorum-sensing molecules, which activate the downstream signaling effectors associated with bitter taste transduction. Isolated nasal chemosensory cells respond to the classic bitter ligand denatonium as well as to the bacterial signals by increasing intracellular Ca2+. Furthermore, these same substances evoke changes in respiration indicative of trigeminal activation. Genetic ablation of either Gα-gustducin or TrpM5, essential elements of the T2R transduction cascade, eliminates the trigeminal response. Because acyl–homoserine lactones serve as quorum-sensing molecules for Gram-negative pathogenic bacteria, detection of these substances by airway chemoreceptors offers a means by which the airway epithelium may trigger an epithelial inflammatory response before the bacteria reach population densities capable of forming destructive biofilms. PMID:20133764

  12. Identification of potential biomarkers for predicting acute dermal irritation by proteomic analysis.

    PubMed

    Zhang, Qihao; Dai, Taoli; Zhang, Lei; Zhang, Minjing; Xiao, Xue; Hu, Hao; Zou, Ping; Liu, Xia; Xiang, Qi; Su, Zhijian; Huang, Yadong; He, Qing-Yu

    2011-11-01

    In vitro alternative tests aiming at replacing the traditional animal test for predicting the irritant potential of chemicals have been developed, but the assessment parameters or endpoints are still not sufficient for analysis. To discover novel endpoints for skin irritation responses, a proteomics approach was used to analyze the protein expression in human keratinocytes exposed to sodium lauryl sulfate in the present study. Among the 20 identified proteins with altered expression, small heat shock protein 27 (HSP27) and superoxide dismutase [Cu-Zn] were down-regulated while cofilin-1 was up-regulated significantly in response to the chemical challenge. Keratinocytes were exposed to acid and basic chemicals for further validation of the proteins. HSP27 displayed the most significant alteration both in mRNA and protein levels, accompanied by nuclear translocation. The irritation also induced an increased production of interleukin-1α in keratinocytes. These findings suggest that these proteins may be combinational biomarkers or additional endpoints for skin hazard assessment. Further investigation into the protein alterations would be helpful for the mechanistic understanding of skin irritation. PMID:21469165

  13. 16 CFR 1500.41 - Method of testing primary irritant substances.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Method of testing primary irritant substances. 1500.41 Section 1500.41 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS HAZARDOUS SUBSTANCES AND ARTICLES; ADMINISTRATION AND ENFORCEMENT REGULATIONS § 1500.41 Method of testing primary...

  14. Gut microbiota influences low fermentable substrate diet efficacy in children with irritable bowel syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We sought to determine whether a low fermentable substrate diet (LFSD) decreases abdominal pain frequency in children with irritable bowel syndrome (IBS) and to identify potential microbial factors related to diet efficacy. Pain symptoms, stooling characteristics, breath hydrogen and methane, whole ...

  15. Irritable bowel syndrome (IBS) subtypes: Nothing resembles less an IBS than another IBS.

    PubMed

    Mearin Manrique, Fermín

    2016-02-01

    Two new members of "IBS Patient Association" met at a meeting. Feeling somewhat lost, not knowing anybody present, they introduced themselves to each other. After exchanging names, one asks the other - "What's your problem?" The other one answers - "I got constipation that laxatives fail to relieve, and my belly, which is always bloated, sometimes hurts so much that I can´t even leave home". Deeply surprised, the first individual inquires - "What are you doing here then?" "Why, I came to this meeting looking for some help for my irritable colon", she answered. "Irritable colon? That's no irritable colon. Irritable bowel syndrome is what I suffer from, and it's diarrhea that won't let me be; can't stop running to the toilet, and cramps just pop up any time". Now both looked surprised. Both thought they had come to the wrong meeting, and both were on the verge of leaving. Luckily, the Association's secretary showed up and explained that both had IBS. PMID:26838485

  16. Comparison of in vitro predictive tests for irritation induced by anionic surfactants.

    PubMed

    Goffin, V; Paye, M; Piérard, G E

    1995-07-01

    Skin compatibility of anionic surfactants may often but not always be predicted by in vitro tests. For instance, the correlation between in vivo and in vitro data is classically hampered in the presence of magnesium. This ion is known to interfere with in vitro skin irritation predictive tests based on protein denaturation. This study was conducted to compare a recently introduced assay, corneosurfametry, with other in vitro tests including the pH-rise of bovine serum albumin, collagen swelling, and zein solubilization tests. Corneosurfametry entails collection of cyanoacrylate skin surface strippings and short contact time with surfactants, followed by staining samples with toluidine blue and basic fuchsin dyes. Measurements are made by reflectance colorimetry. Data show that irritation potentials predicted by corneosurfametry agree with those obtained by established in vivo and in vitro irritation tests. Moreover, corneosurfametry data are not artificially lowered by addition of magnesium in surfactant solutions. In conclusion, corneosurfametry should be viewed as one of the realistic predictive tests for surfactant irritancy. PMID:7493460

  17. 30 CFR 57.15006 - Protective equipment and clothing for hazards and irritants.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Protective equipment and clothing for hazards and irritants. 57.15006 Section 57.15006 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND...

  18. 30 CFR 56.15006 - Protective equipment and clothing for hazards and irritants.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Protective equipment and clothing for hazards and irritants. 56.15006 Section 56.15006 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL...

  19. Effects of Orchard Pesticides on Galendromus occidentalis (Acari: Phytoseiidae): Repellency and Irritancy.

    PubMed

    Beers, Elizabeth H; Schmidt-Jeffris, Rebecca A

    2015-02-01

    The effects of repellency or irritancy in Galendromus occidentalis (Nesbitt) were studied for three rates of 16 pesticides commonly used in apple production. Adult female mites were exposed to residues in a series of choice bioassays (treated and untreated half of bean leaf disks). Novaluron, carbaryl, mancozeb+copper hydroxide, and sulfur were the most repellent materials to G. occidentalis, with females consistently avoiding the treated side of the leaf disk. Spirotetramat, flubendiamide, and cyantriniliprole caused an intermediate or inconsistent degree of repellency; azinphosmethyl, lambda-cyhalothrin, acetamiprid, thiacloprid, imidacloprid, spinetoram, spinosad, and chlorantriniliprole caused little to no repellency. Irritancy (running off of the disk, as opposed to resting on the untreated half) was the most pronounced in the acetamiprid and lambda-cyhalothrin treatments. Acute toxicity (within the 6 h test period) was highest in the lambda-cyhalothrin and spinetoram treatments; in the former case, the mortality at all rates tested was substantial enough to interfere with the measurement of behavioral effects. Although irritancy may be considered the more extreme form of repellency, there were several pesticides (carbaryl, cyantraniliprole, mancozeb+copper hydroxide, novaluron) where a moderate to high degree of repellency did not correspond to a high degree of irritancy. Similarly, repellency was not consistently related to acute toxicity; one of the most repellent materials (novaluron) was not acutely toxic. Behavioral effects may help explain instances where lethal or sublethal bioassays do not fully predict the effects of pesticides seen in orchard use. PMID:26470128

  20. 30 CFR 57.15006 - Protective equipment and clothing for hazards and irritants.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Protective equipment and clothing for hazards... AND NONMETAL MINES Personal Protection Surface and Underground § 57.15006 Protective equipment and clothing for hazards and irritants. Special protective equipment and special protective clothing shall...

  1. 30 CFR 57.15006 - Protective equipment and clothing for hazards and irritants.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Protective equipment and clothing for hazards... AND NONMETAL MINES Personal Protection Surface and Underground § 57.15006 Protective equipment and clothing for hazards and irritants. Special protective equipment and special protective clothing shall...

  2. 30 CFR 56.15006 - Protective equipment and clothing for hazards and irritants.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Protective equipment and clothing for hazards... NONMETAL MINES Personal Protection § 56.15006 Protective equipment and clothing for hazards and irritants. Special protective equipment and special protective clothing shall be provided, maintained in a...

  3. 30 CFR 56.15006 - Protective equipment and clothing for hazards and irritants.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Protective equipment and clothing for hazards... NONMETAL MINES Personal Protection § 56.15006 Protective equipment and clothing for hazards and irritants. Special protective equipment and special protective clothing shall be provided, maintained in a...

  4. 30 CFR 56.15006 - Protective equipment and clothing for hazards and irritants.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Protective equipment and clothing for hazards... NONMETAL MINES Personal Protection § 56.15006 Protective equipment and clothing for hazards and irritants. Special protective equipment and special protective clothing shall be provided, maintained in a...

  5. 30 CFR 57.15006 - Protective equipment and clothing for hazards and irritants.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Protective equipment and clothing for hazards... AND NONMETAL MINES Personal Protection Surface and Underground § 57.15006 Protective equipment and clothing for hazards and irritants. Special protective equipment and special protective clothing shall...

  6. 30 CFR 56.15006 - Protective equipment and clothing for hazards and irritants.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Protective equipment and clothing for hazards... NONMETAL MINES Personal Protection § 56.15006 Protective equipment and clothing for hazards and irritants. Special protective equipment and special protective clothing shall be provided, maintained in a...

  7. 30 CFR 57.15006 - Protective equipment and clothing for hazards and irritants.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Protective equipment and clothing for hazards... AND NONMETAL MINES Personal Protection Surface and Underground § 57.15006 Protective equipment and clothing for hazards and irritants. Special protective equipment and special protective clothing shall...

  8. Methodological issues in the study of intestinal microbiota in irritable bowel syndrome.

    PubMed

    Taverniti, Valentina; Guglielmetti, Simone

    2014-07-21

    Irritable bowel syndrome (IBS) is an intestinal functional disorder with the highest prevalence in the industrialized world. The intestinal microbiota (IM) plays a role in the pathogenesis of IBS and is not merely a consequence of this disorder. Previous research efforts have not revealed unequivocal microbiological signatures of IBS, and the experimental results are contradictory. The experimental methodologies adopted to investigate the complex intestinal ecosystem drastically impact the quality and significance of the results. Therefore, to consider the methodological aspects of the research on IM in IBS, we reviewed 29 relevant original research articles identified through a PubMed search using three combinations of keywords: "irritable bowel syndrome + microflora", "irritable bowel syndrome + microbiota" and "irritable bowel syndrome + microbiome". For each study, we reviewed the quality and significance of the scientific evidence obtained with respect to the experimental method adopted. The data obtained from each study were compared with all considered publications to identify potential inconsistencies and explain contradictory results. The analytical revision of the studies referenced in the present review has contributed to the identification of microbial groups whose relative abundance significantly alters IBS, suggesting that these microbial groups could be IM signatures for this syndrome. The identification of microbial biomarkers in the IM can be advantageous for the development of new diagnostic tools and novel therapeutic strategies for the treatment of different subtypes of IBS. PMID:25083056

  9. [Primary results of the reflexotherapy in the syndrome of irritable colon. Preliminary note5].

    PubMed

    Di Cicco, M; Magnani, G; Roccia, L

    1976-06-01

    After stressing the uncertainties of classifying the syndrome exactly and the part played by psychosomatism in its aetiopathogenesis, some forms of acupuncture have been attempted as alternatives to psychodrugs and antispastic substances. 50 cases are examined in which diagnosis of irritable colon was confirmed by thorough clinical and laboratory examinations, use is also being made of appropriate computerizable tables. PMID:934538

  10. Separation of retinoid-induced epidermal and dermal thickening from skin irritation

    PubMed Central

    Fligiel, Helene; Zhang, Jian; Aslam, Muhammad Nadeem; Lu, Yi; Dehne, Lindsay A.; Keller, Evan T.

    2010-01-01

    The ability of the synthetic retinoid MDI-301, in which the carboxylic acid of 9-cis-retinoic acid (9-cis-RA) is replaced with an ester linkage, to induce epidermal and dermal thickening and skin irritation (erythema and flaking) in hairless (rhino) mice following its topical application was investigated in comparison with that of 14-all-trans-retinoic acid (14-all-trans-RA) and 9-cis-RA. MDI-301 induced epidermal proliferation leading to a thickened epidermis. Treated animals also demonstrated a prominent band of organized connective tissue immediately below the epidermis. In its ability to induce epidermal thickening, MDI-301 was quantitatively similar to 14-all-trans-RA and 9-cis-RA. However, unlike 14-all-trans-RA and 9-cis-RA, which produced skin irritation associated with a perivascular influx of mononuclear leukocytes into the dermis, there was no evidence of irritation with MDI-301 and little leukocyte infiltration. Intraperitoneal injection of either 14-all-trans-RA or MDI-301 also resulted in epidermal and dermal thickening. Irritation of skin was not observed in these animals but splenomegaly was prominent in animals treated with either agent. PMID:14564458

  11. The influence of hard water (calcium) and surfactants on irritant contact dermatitis.

    PubMed

    Warren, R; Ertel, K D; Bartolo, R G; Levine, M J; Bryant, P B; Wong, L F

    1996-12-01

    Although the induction of irritant contact dermatitis has been extensively studied for surfactants, the role of the environmental factor water hardness (i.e., calcium content) on the induction process has not received attention. Our objective was to investigate differences in surfactant-induced irritant skin reactions from cumulative exposure to 3 different personal cleansing agents and determine whether the irritation potential can be affected by the hardness of the water. 2 commonly used exaggerated washing procedures were variously employed to evaluate representative sodium soap, triethanolamine-soap, or synthetic detergent cleansers under conditions where the water hardness varied from 0-grain to 11-grain (gr). Subjects were clinically evaluated for skin dryness, skin redness, and instrumentally for hydration. Soap binding to skin was quantified using Fourier transform infrared reflectance spectroscopy. Using the more mild wash procedure, skin sites treated under conditions of hard, 11 gr water were significantly drier, had more erythema, and were less hydrated than corresponding sites treated with deionized 0 gr water. All 3 surfactant cleanser behaved similarly. We also found the hardness of the rinse water to be the more significant factor versus that of the wash water. Effect of water hardness on soap binding to skin revealed a similar outcome. Under a more exaggerated wash condition the relationship between water hardness and irritation broke down. PMID:9118628

  12. Increased gastrointestinal permeability and gut inflammation in children with functional abdominal pain and Irritable Bowel Syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To determine gastrointestinal (GI) permeability and fecal calprotectin concentration in children 7 to 10 years of age with functional abdominal pain and irritable bowel syndrome (FAP/IBS) versus control subjects and ascertain potential relationships with pain symptoms and stooling, GI permeability a...

  13. The Affective Reactivity Index: A Concise Irritability Scale for Clinical and Research Settings

    ERIC Educational Resources Information Center

    Stringaris, Argyris; Goodman, Robert; Ferdinando, Sumudu; Razdan, Varun; Muhrer, Eli; Leibenluft, Ellen; Brotman, Melissa A.

    2012-01-01

    Background: Irritable mood has recently become a matter of intense scientific interest. Here, we present data from two samples, one from the United States and the other from the United Kingdom, demonstrating the clinical and research utility of the parent- and self-report forms of the Affective Reactivity Index (ARI), a concise dimensional measure…

  14. Associations among gut permeability, inflammatory markers, and symptoms in patients with irritable bowel syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Alterations in gastrointestinal (GI) permeability and immune measures are present in some patients with irritable bowel syndrome (IBS) but the relationship to symptoms is poorly defined. In adults with IBS, we compared permeability, unstimulated peripheral blood monocyte (PBMC) interleukin-10 (IL-10...

  15. Characterization of Spatial Repellent, Contact Irritant and Toxicant Chemical Actions of Standard Vector Control Compounds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A previously described modular high-throughput screening system (HITTS) was used to characterize the spatial repellent, contact irritant and toxicant chemical actions of 14 compounds with a history of use in vector control. The response of F1-F4 Aedes aegypti to various concentrations of four organo...

  16. Autonomic nervous system function in young children with functional abdominal pain or irritable bowel syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adults with irritable bowel syndrome (IBS) have been reported to have alterations in autonomic nervous system function as measured by vagal activity via heart rate variability. Whether the same is true for children is unknown. We compared young children 7 to 10 years of age with functional abdominal...

  17. Brief Report: Retrospective Case Series of Oxcarbazepine for Irritability/Agitation Symptoms in Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Douglas, Jessica F.; Sanders, Kevin B.; Benneyworth, M. Hannah; Smith, Jessica L.; DeJean, Virginia M.; McGrew, Susan G.; Veenstra-VanderWeele, Jeremy

    2013-01-01

    We examined response to oxcarbazepine prescribed for irritability/agitation symptoms in a retrospective case series of 30 patients with Autism Spectrum Disorder (ASD). The average patient was 12.0 years old (range 5-21) and taking two other psychotropic medications (range 0-4). Fourteen patients (47 %) had a clinical global impression of…

  18. Can a positive photopatch test be elicited by subclinical irritancy or allergy plus suberythemal UV exposure?

    PubMed

    Beattie, P E; Traynor, N J; Woods, J A; Dawe, R S; Ferguson, J; Ibbotson, S H

    2004-01-01

    Photopatch test (PhPT) interpretation is difficult and clinical relevance is not always apparent. A positive PhPT may reflect photocontact allergy or phototoxicity. We hypothesized that it may also reflect the additive or synergistic effects of a suberythemal reaction to a contact irritant [e.g. sodium lauryl sulfate (SLS)] or allergen (e.g. nickel) and suberythemal UV exposure. 10 nickel allergic volunteers had duplicate SLS and nickel series applied on either side of the back for 24 h and 48 h, respectively. After removal, one side was irradiated with 5 J/cm(2) UVA or the dose below the minimal erythema dose for solar-simulated radiation (SSR). The minimal irritancy dose (MID) for SLS and the minimal allergenic dose (MAD) for nickel were determined visually and objectively by erythema meter. While photoaugmentation of subclinical contact allergy or irritancy occurred in some subjects, photosuppression occurred in roughly an equal number. UVA changed the nickel MAD at 48 h in 2 of 5 volunteers but not the SLS MID. SSR changed the nickel MAD in 4 of 5 and the SLS MID in 3 of 5. 2 subjects (none after UVA) showed erythema only in the irradiated set of patches, which could have been interpreted as a positive PhPT. We have demonstrated photoaugmentation and photosuppression of contact allergy and irritancy, which could result in false-positive or false-negative interpretation of PhPTs. PMID:15606647

  19. Longitudinal Outcome of Youth Oppositionality: Irritable, Headstrong, and Hurtful Behaviors Have Distinctive Predictions

    ERIC Educational Resources Information Center

    Stringaris, Argyris; Goodman, Robert

    2009-01-01

    A longitudinal design that compares data from two British national surveys and their follow-ups reveal that an irritable dimension of oppositional behavior is the sole predictor of emotional disorder at follow-up. The headstrong dimension is the predictor of attention-deficit hyperactivity disorder while the hurtful dimension is a strong predictor…

  20. Methodological issues in the study of intestinal microbiota in irritable bowel syndrome

    PubMed Central

    Taverniti, Valentina; Guglielmetti, Simone

    2014-01-01

    Irritable bowel syndrome (IBS) is an intestinal functional disorder with the highest prevalence in the industrialized world. The intestinal microbiota (IM) plays a role in the pathogenesis of IBS and is not merely a consequence of this disorder. Previous research efforts have not revealed unequivocal microbiological signatures of IBS, and the experimental results are contradictory. The experimental methodologies adopted to investigate the complex intestinal ecosystem drastically impact the quality and significance of the results. Therefore, to consider the methodological aspects of the research on IM in IBS, we reviewed 29 relevant original research articles identified through a PubMed search using three combinations of keywords: “irritable bowel syndrome + microflora”, “irritable bowel syndrome + microbiota” and “irritable bowel syndrome + microbiome”. For each study, we reviewed the quality and significance of the scientific evidence obtained with respect to the experimental method adopted. The data obtained from each study were compared with all considered publications to identify potential inconsistencies and explain contradictory results. The analytical revision of the studies referenced in the present review has contributed to the identification of microbial groups whose relative abundance significantly alters IBS, suggesting that these microbial groups could be IM signatures for this syndrome. The identification of microbial biomarkers in the IM can be advantageous for the development of new diagnostic tools and novel therapeutic strategies for the treatment of different subtypes of IBS. PMID:25083056

  1. Improved procedures for in vitro skin irritation testing of sticky and greasy natural botanicals.

    PubMed

    Molinari, J; Eskes, C; Andres, E; Remoué, N; Sá-Rocha, V M; Hurtado, S P; Barrichello, C

    2013-02-01

    Skin irritation evaluation is an important endpoint for the safety assessment of cosmetic ingredients required by various regulatory authorities for notification and/or import of test substances. The present study was undertaken to investigate possible protocol adaptations of the currently validated in vitro skin irritation test methods based on reconstructed human epidermis (RhE) for the testing of plant extracts and natural botanicals. Due to their specific physico-chemical properties, such as lipophilicity, sticky/buttery-like texture, waxy/creamy foam characteristics, normal washing procedures can lead to an incomplete removal of these materials and/or to mechanical damage to the tissues, resulting in an impaired prediction of the true skin irritation potential of the materials. For this reason different refined washing procedures were evaluated for their ability to ensure appropriate removal of greasy and sticky substances while not altering the normal responses of the validated RhE test method. Amongst the different procedures evaluated, the use of a SDS 0.1% PBS solution to remove the sticky and greasy test material prior to the normal washing procedures was found to be the most suitable adaptation to ensure efficient removal of greasy and sticky in-house controls without affecting the results of the negative control. The predictive capacity of the refined SDS 0.1% washing procedure, was investigated by using twelve oily and viscous compounds having known skin irritation effects supported by raw and/or peer reviewed in vivo data. The normal washing procedure resulted in 8 out of 10 correctly predicted compounds as compared to 9 out of 10 with the refined washing procedures, showing an increase in the predictive ability of the assay. The refined washing procedure allowed to correctly identify all in vivo skin irritant materials showing the same sensitivity as the normal washing procedures, and further increased the specificity of the assay from 5 to 6 correct

  2. Chemosensory irritations and pulmonary effects of acute exposure to emissions from oriented strand board.

    PubMed

    Gminski, Richard; Marutzky, Rainer; Kevekordes, Sebastian; Fuhrmann, Frank; Bürger, Werner; Hauschke, Dieter; Ebner, Winfried; Mersch-Sundermann, Volker

    2011-09-01

    Due to the reduction of air change rates in low-energy houses, the contribution to indoor air quality of volatile organic compounds (VOCs) emitting from oriented strand boards (OSB) has become increasingly important. The aim of this study was to evaluate sensory irritations, pulmonary effects and odor annoyance of emissions from OSB in healthy human volunteers compared to clean air. Twenty-four healthy non-smokers were exposed to clean air and OSB emissions for 2 h under controlled conditions in a 48 m(3) test chamber at three different time points: to fresh OSB panels and to the same panels after open storage for 2 and 8 weeks. Chemosensory irritation, exhaled nitric oxide (NO) concentration, eye blink frequency, lung function and subjective perception of irritation of eyes, nose and throat were examined before, during and after exposure. Additionally, olfactory perception was investigated. Total VOC exposure concentrations reached 8.9 ± 0.8 mg/m(3) for the fresh OSB panels. Emissions consisted predominantly of α-pinene, Δ(3)-carene and hexanal. Two-hour exposure to high VOC concentrations revealed no irritating or pulmonary effects. All the subjective ratings of discomfort were at a low level and the medians did not exceed the expression 'hardly at all.' Only the ratings for smell of emissions increased significantly during exposure in comparison to clean air. In conclusion, exposure of healthy volunteers to OSB emissions did not elicit sensory irritations or pulmonary effects up to a VOC concentration of about 9 mg/m(3). Sensory intensity of OSB emissions in the chamber air was rated as 'neutral to pleasant.' PMID:21071553

  3. Epithelium-fibroblast co-culture for assessing mucosal irritancy of metals used in dentistry.

    PubMed

    Schmalz, G; Arenholt-Bindslev, D; Hiller, K A; Schweikl, H

    1997-02-01

    No valid animal or in vitro model exists to assess the potential mucosal irritancy of dental materials. However, recently, a commercially available model system based on a recombined co-culture of human fibroblasts and human epithelial cells has been introduced for evaluating the time-dependent irritancy of cosmetic products. Cell viability and prostaglandin E2 (PGE2) release from the cells were used as markers for the irritative potential of test materials. The objective of the present study was to evaluate the suitability of this model for monitoring the irritative potential of metals and cast alloys used in dentistry. The human fibroblast-keratinocyte co-cultures were exposed to test specimens fabricated from copper, zinc, palladium, nickel, tin, cobalt, indium, a high noble cast alloy, and from a dental ceramic. Cell survival rates decreased after exposure to copper (14-25%), cobalt (60%), zinc (63%), indium (85%), nickel (87%), and the non-oxidized and oxidized high noble cast alloy (87%/90%) compared to untreated control cultures. Dental ceramic, palladium and tin did not influence cell viability. In parallel, the PGE2 release was continuously monitored up to 24 h using a competitive displacement enzyme immunoassay. PGE2 release increased most highly in the cultures exposed to copper (6-25 fold), cobalt (7 fold), indium (4 fold), and zinc (2 fold) compared to untreated control cultures. The PGE2 determination proved to be a non-destructive method for continuous monitoring of cell reactions in the same culture. The model used seems promising for evaluating the time-dependent mucosal irritancy of dental cast alloys. PMID:9085034

  4. Contribution of Blastocystishominis subtypes and associated inflammatory factors in development of irritable bowel syndrome.

    PubMed

    Azizian, Marzieh; Basati, Gholam; Abangah, Ghobad; Mahmoudi, Mohammad Reza; Mirzaei, Asad

    2016-05-01

    Blastocystis hominis with worldwide distribution is a human intestinal protozoa found in all countries. There have been differences in the severity of the pathogenesis of various Blastocystis spp. and a concomitant variation in the plasma concentration of the cytokines in patients with irritable bowel syndrome. In the present study, we aimed to demonstrate the contribution of B. hominis subtypes in the development of irritable bowel syndrome. Stool samples were collected from patients with gastrointestinal disorders. All samples were evaluated through native-lugol method. Total DNA was extracted. A PCR protocol was developed to amplify a specific region of the SSU ribosomal DNA (rDNA) gene. Serum levels of IL-6 and TNF-α were determined by immunoassay methods. The ClustalW algorithm was applied to align and blast the nucleotide sequences of the amplified region of the SSU rDNA gene. To evaluate the phylogenetic and molecular evolutionary of the nucleotide sequences, we used the MEGA software. In this study, we found 26 haplotypes of B. hominis in the studied samples which were collectively belong to five subtypes (ST1, ST2 in patients without irritable bowel syndrome vs. ST3 and two unknown subtypes in patients with irritable bowel syndrome). Result of ELISA showed a high level of IL-6 and TNF-α in the serum of patients with irritable bowel syndrome. The genetic heterogeneity of B. hominis and the existence of different subtypes of the protozoan in patients with IBS may shed light to the fact that some subtypes of parasites may involve in the pathogenesis of IBS. PMID:26841770

  5. Relevance and reliability of the PREDISAFE assay in the COLIPA eye irritation validation program (phase 1).

    PubMed

    Courtellemont, P; Hébert, P; Biesse, J P; Castelli, D; Friteau, L; Serrano, J; Robles, C

    1999-04-01

    The 6th Amendment of the European Directive on Cosmetics induces a potential ban on animal testing for cosmetic ingredients and finished products. In this new context, COLIPA (The European Cosmetic Toiletry and Perfumery Association) has initiated an international multicentric study with the main goal of validating available alternatives to in vitro methods for assessing the eye irritation potential of cosmetic raw materials and formulations. In order to test undiluted and hydrophobic ingredients and formulations, a cytotoxicity test named PREDISAFE was incorporated into our internal battery of in vitro tests for 3 years. This cell culture test based on the neutral red release procedure was prevalidated with several cosmetic formulations and used systematically by comparison with internal benchmarks. In this article, the defined prediction model and the protocol used in the COLIPA eye irritation program are described, and furthermore the PREDISAFE assay results obtained during Phase I of the above mentioned study are presented and discussed in detail. The statistical analysis proves clearly a great interest in the PREDISAFE test for the prediction of eye irritation potential of cosmetic formulations. Its strong compatibility for a wide category of finished products associated with its ease of use offer relevant advantages for a routine use in the ocular irritancy screening in the cosmetics industry. This paper also explains the reasons for false negative and false positive in vitro tests results and describes possible technical modifications to avoid these wrong predictions. At the end, some recommendations for the Phase II of the COLIPA study are considered with the main objective to prove that a multivariable analysis could be useful to find the best battery of in vitro assays for acceptance by the regulators for the replacement of the Draize eye irritation test. PMID:20654488

  6. TRPV4 is necessary for trigeminal irritant pain and functions as a cellular formalin receptor

    PubMed Central

    Chen, Yong; Kanju, Patrick; Fang, Quan; Lee, Suk Hee; Parekh, Puja K.; Lee, Whasil; Moore, Carlene; Brenner, Daniel; Gereau, Robert W.; Wang, Fan; Liedtke, Wolfgang

    2014-01-01

    Detection of external irritants by head nociceptor neurons has deep evolutionary roots. Irritant-induced aversive behavior is a popular pain model in laboratory animals. It is used widely in the formalin-model, where formaldehyde is injected into the rodent paw, eliciting quantifiable nocifensive behavior that has a direct, tissue-injury-evoked phase, and a subsequent tonic phase caused by neural maladaptation. The formalin model has elucidated many anti-pain compounds and pain-modulating signaling pathways. We have adopted this model to trigeminally-innervated territories in mice. Also, we have examined the involvement of TRPV4 channels in formalin-evoked trigeminal pain behavior, because TRPV4 is abundantly expressed in trigeminal ganglion (TG) sensory neurons, also because we have recently defined TRPV4’s role in response to air-borne irritants, and in a model for temporomandibular joint pain. We found TRPV4 to be important for trigeminal nocifensive behavior evoked by formalin whiskerpad injections. This conclusion is supported by studies with Trpv4−/− mice and TRPV4-specific antagonists. Our results imply TRPV4 in MEK-ERK activation in TG sensory neurons. Furthermore, cellular studies in primary TG neurons and in heterologous TRPV4-expressing cells suggest that TRPV4 can be activated directly by formalin to gate Ca++. Using TRPA1-blocker and Trpa1−/− mice, we found that both TRP channels co-contribute to the formalin trigeminal pain response. These results imply TRPV4 as an important signaling molecule in irritation-evoked trigeminal pain. TRPV4-antagonistic therapies can therefore be envisioned as novel analgesics, possibly for specific targeting of trigeminal pain disorders, such as migraine, headaches, TMJ, facial and dental pain, and irritation of trigeminally-innervated surface epithelia. PMID:25281928

  7. Bronchial asthma and COPD due to irritants in the workplace - an evidence-based approach

    PubMed Central

    2012-01-01

    Background Respiratory irritants represent a major cause of occupational obstructive airway diseases. We provide an overview of the evidence related to irritative agents causing occupational asthma or occupational COPD. Methods We searched MEDLINE via PubMed. Reference lists of relevant reviews were also screened. The SIGN grading system was used to rate the quality of each study. The modified RCGP three-star system was used to grade the body of evidence for each irritant agent regarding its causative role in either occupational asthma or occupational COPD. Results A total of 474 relevant papers were identified, covering 188 individual agents, professions or work-sites. The focus of most of the studies and the predominant diagnosis was occupational asthma, whereas occupational COPD arose only incidentally. The highest level assigned using the SIGN grading was 2+ (well-conducted systematic review, cohort or case–control study with a low risk of confounding or bias). According to the modified RCGP three-star grading, the strongest evidence of association with an individual agent, profession or work-site (“**”) was found for 17 agents or work-sites, including benzene-1,2,4-tricarboxylicacid-1,2-anhydride, chlorine, platinum salt, isocyanates, cement dust, grain dust, animal farming, environmental tobacco smoke, welding fumes or construction work. Phthalic anhydride, glutaraldehyde, sulphur dioxide, cotton dust, cleaning agents, potrooms, farming (various), foundries were found to be moderately associated with occupational asthma or occupational COPD (“*[+]”). Conclusion This study let us assume that irritant-induced occupational asthma and especially occupational COPD are considerably underreported. Defining the evidence of the many additional occupational irritants for causing airway disorders will be the subject of continued studies with implications for diagnostics and preventive measures. PMID:23013890

  8. Novel vehicle based on cubosomes for ophthalmic delivery of flurbiprofen with low irritancy and high bioavailability

    PubMed Central

    Han, Shun; Shen, Jin-qiu; Gan, Yong; Geng, Hai-ming; Zhang, Xin-xin; Zhu, Chun-liu; Gan, Li

    2010-01-01

    Aim: To develop a novel vehicle based on cubosomes as an ophthalmic drug delivery system for flurbiprofen (FB) to reduce ocular irritancy and improve bioavailability. Methods: FB-loaded cubosomes were prepared using hot and high-pressure homogenization. Cubosomes were then characterized by particle size, zeta potential, encapsulation efficiency, particle morphology, inner cubic structure and in vitro release. Corneal permeation was evaluated using modified Franz-type cells. Ocular irritation was then evaluated using both the Draize method and histological examination. The ocular pharmacokinetics of FB was determined using microdialysis. Results: The particle size of each cubosome formulation was about 150 nm. A bicontinuous cubic phase of cubic P-type was determined using cryo-transmission electron microscopy (cryo-TEM) observation and small angle X-ray scattering (SAXS) analysis. In vitro corneal permeation study revealed that FB formulated in cubosomes exhibited 2.5-fold (F1) and 2.0-fold (F2) increase in Papp compared with FB PBS. In the ocular irritation test, irritation scores for each group were less than 2, indicating that all formulations exhibited excellent ocular tolerance. Histological examination revealed that neither the structure nor the integrity of the cornea was visibly affected after incubation with FB cubosomes. The AUC of FB administered as FB cubosome F2 was 486.36±38.93 ng·mL−1·min·μg−1, which was significantly higher than that of FB Na eye drops (P<0.01). Compared with FB Na eye drops, the Tmax of FB cubosome F2 was about 1.6-fold higher and the MRT was also significantly longer (P<0.001). Conclusion: This novel low-irritant vehicle based on cubosomes might be a promising system for effective ocular drug delivery. PMID:20686524

  9. Anhedonia, but not Irritability, Is Associated with Illness Severity Outcomes in Adolescent Major Depression

    PubMed Central

    Johnson, Amy R.; Alonso, Carmen M.; Evans, Lori K.; Babb, James S.; Klein, Rachel G.

    2015-01-01

    Abstract Objectives: Unlike adult major depressive disorder (MDD) which requires anhedonia or depressed mood for diagnosis, adolescent MDD can be sufficiently diagnosed with irritability in the absence of the former symptoms. In addition, the current Diagnostic and Statistical Manual of Mental Disorders (DSM) schema does not account for the interindividual variability of symptom severity among depressed adolescents. This practice has contributed to the high heterogeneity and diagnostic complexity of adolescent MDD. Here, we sought to examine relationships between two core symptoms of adolescent MDD – irritability and anhedonia, assessed both quantitatively and categorically – and other clinical correlates among depressed adolescents. Methods: Ninety adolescents with MDD (51 females), ages 12–20, were enrolled. Anhedonia and irritability scores were quantified by summing related items on the Children's Depression Rating Scale-Revised and the Beck Depression Inventory. Extremes of score distribution were defined as high or low irritability/anhedonia subgroups. A significance level of p=0.01 was set to adjust for the five comparisons. Results: Despite all subjects exhibiting moderate to severe MDD, both irritability and anhedonia scores manifested a full and normally distributed severity range including the lowest values possible. However, only anhedonia severity was associated with more severe clinical outcomes, including greater overall illness severity (p<0.001), suicidality scores (p<0.001), episode duration (p=0.006), and number of MDD episodes (p=0.01). Similarly, only the high-anhedonia subgroup manifested more severe outcomes; specifically, greater illness severity (p<0.0001), number of MDD episodes (p=0.01), episode duration (p=0.01), and suicidality scores (p=0.0001). Conclusions: Our findings suggest the significance of anhedonia as a hallmark of adolescent MDD and the need to incorporate dimensional analyses. These data are preliminary, and future

  10. Non-occlusive topical exposure of human skin in vitro as model for cytotoxicity testing of irritant compounds.

    PubMed

    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. PMID:26446981

  11. The EpiOcular Eye Irritation Test (EIT) for hazard identification and labelling of eye irritating chemicals: protocol optimisation for solid materials and the results after extended shipment.

    PubMed

    Kaluzhny, Yulia; Kandárová, Helena; Handa, Yuki; DeLuca, Jane; Truong, Thoa; Hunter, Amy; Kearney, Paul; d'Argembeau-Thornton, Laurence; Klausner, Mitchell

    2015-05-01

    The 7th Amendment to the EU Cosmetics Directive and the EU REACH Regulation have reinforced the need for in vitro ocular test methods. Validated in vitro ocular toxicity tests that can predict the human response to chemicals, cosmetics and other consumer products are required for the safety assessment of materials that intentionally, or inadvertently, come into contact with the eye. The EpiOcular Eye Irritation Test (EIT), which uses the normal human cell-based EpiOcular™ tissue model, was developed to address this need. The EpiOcular-EIT is able to discriminate, with high sensitivity and accuracy, between ocular irritant/corrosive materials and those that require no labelling. Although the original EpiOcular-EIT protocol was successfully pre-validated in an international, multicentre study sponsored by COLIPA (the predecessor to Cosmetics Europe), data from two larger studies (the EURL ECVAM-COLIPA validation study and an independent in-house validation at BASF SE) resulted in a sensitivity for the protocol for solids that was below the acceptance criteria set by the Validation Management Group (VMG) for eye irritation, and indicated the need for improvement of the assay's sensitivity for solids. By increasing the exposure time for solid materials from 90 minutes to 6 hours, the optimised EpiOcular-EIT protocol achieved 100% sensitivity, 68.4% specificity and 84.6% accuracy, thereby meeting all the acceptance criteria set by the VMG. In addition, to satisfy the needs of Japan and the Pacific region, the EpiOcular-EIT method was evaluated for its performance after extended shipment and storage of the tissues (4-5 days), and it was confirmed that the assay performs with similar levels of sensitivity, specificity and reproducibility in these circumstances. PMID:25995013

  12. Eye Irritation Test (EIT) for Hazard Identification of Eye Irritating Chemicals using Reconstructed Human Cornea-like Epithelial (RhCE) Tissue Model.

    PubMed

    Kaluzhny, Yulia; Kandárová, Helena; d'Argembeau-Thornton, Laurence; Kearney, Paul; Klausner, Mitchell

    2015-01-01

    To comply with the Seventh Amendment to the EU Cosmetics Directive and EU REACH legislation, validated non-animal alternative methods for reliable and accurate assessment of ocular toxicity in man are needed. To address this need, we have developed an eye irritation test (EIT) which utilizes a three dimensional reconstructed human cornea-like epithelial (RhCE) tissue model that is based on normal human cells. The EIT is able to separate ocular irritants and corrosives (GHS Categories 1 and 2 combined) and those that do not require labeling (GHS No Category). The test utilizes two separate protocols, one designed for liquid chemicals and a second, similar protocol for solid test articles. The EIT prediction model uses a single exposure period (30 min for liquids, 6 hr for solids) and a single tissue viability cut-off (60.0% as determined by the MTT assay). Based on the results for 83 chemicals (44 liquids and 39 solids) EIT achieved 95.5/68.2/ and 81.8% sensitivity/specificity and accuracy (SS&A) for liquids, 100.0/68.4/ and 84.6% SS&A for solids, and 97.6/68.3/ and 83.1% for overall SS&A. The EIT will contribute significantly to classifying the ocular irritation potential of a wide range of liquid and solid chemicals without the use of animals to meet regulatory testing requirements. The EpiOcular EIT method was implemented in 2015 into the OECD Test Guidelines as TG 492. PMID:26325674

  13. Eye Irritation Test (EIT) for Hazard Identification of Eye Irritating Chemicals using Reconstructed Human Cornea-like Epithelial (RhCE) Tissue Model

    PubMed Central

    Kaluzhny, Yulia; Kandárová, Helena; d’Argembeau-Thornton, Laurence; Kearney, Paul; Klausner, Mitchell

    2015-01-01

    To comply with the Seventh Amendment to the EU Cosmetics Directive and EU REACH legislation, validated non-animal alternative methods for reliable and accurate assessment of ocular toxicity in man are needed. To address this need, we have developed an eye irritation test (EIT) which utilizes a three dimensional reconstructed human cornea-like epithelial (RhCE) tissue model that is based on normal human cells. The EIT is able to separate ocular irritants and corrosives (GHS Categories 1 and 2 combined) and those that do not require labeling (GHS No Category). The test utilizes two separate protocols, one designed for liquid chemicals and a second, similar protocol for solid test articles. The EIT prediction model uses a single exposure period (30 min for liquids, 6 hr for solids) and a single tissue viability cut-off (60.0% as determined by the MTT assay). Based on the results for 83 chemicals (44 liquids and 39 solids) EIT achieved 95.5/68.2/ and 81.8% sensitivity/specificity and accuracy (SS&A) for liquids, 100.0/68.4/ and 84.6% SS&A for solids, and 97.6/68.3/ and 83.1% for overall SS&A. The EIT will contribute significantly to classifying the ocular irritation potential of a wide range of liquid and solid chemicals without the use of animals to meet regulatory testing requirements. The EpiOcular EIT method was implemented in 2015 into the OECD Test Guidelines as TG 492. PMID:26325674

  14. The Importance of Irritability as a Symptom of Major Depressive Disorder: Results from the National Comorbidity Survey Replication

    PubMed Central

    Fava, Maurizio; Hwang, Irving; Rush, A. John; Sampson, Nancy; Walters, Ellen E.; Kessler, Ronald C.

    2010-01-01

    Irritability is a diagnostic symptom of child-adolescent but not adult major depressive disorder (MDD) in both the DSM-IV and ICD-10 systems. We explore the importance of irritability for sub-typing adult DSM-IV MDD in the National Comorbidity Survey Replication (NCS-R), a national US adult household survey. The WHO Composite International Diagnostic Interview (CIDI) was used to assess prevalence of many DSM-IV disorders in the lifetime and in the year before interview (12-month prevalence). MDD was assessed conventionally (i.e., requiring either persistent sadness or loss of interest), but with irritability included as one of the Criterion A symptoms. We also considered the possibility that irritability might be a diagnostic symptom of adult MDD (i.e., detect cases who had neither sad mood nor loss of interest). Twelve-month MDD symptom severity was assessed with the Quick Inventory of Depressive Symptomatology and role impairment with the Sheehan Disability Scale. After excluding bipolar spectrum disorders, irritability during depressive episodes was reported by roughly half of respondents with lifetime DSM-IV MDD. Irritability in the absence of either sad mood or loss of interest, in comparison, was rare. Irritability in MDD was associated with early age-of-onset, lifetime persistence, comorbidity with anxiety and impulse-control disorders, fatigue and self-reproach during episodes, and disability. Irritability was especially common in MDD among respondents in the age range 18–44 and students. Further investigation is warranted of distinct family aggregation, risk factors, and treatment response. Consideration should also be given to including irritability as a non-diagnostic symptom of adult MDD in DSM-V and ICD-11. PMID:19274052

  15. Evaluation of skin irritation and sensitization of two diol solutions used as experimental dentin primers in humans and guinea pigs.

    PubMed

    Kurihara, A; Manabe, A; Katsuno, K; Itoh, K; Hisamitsu, H; Wakumoto, S; Yoshida, T

    1996-12-01

    The purpose of the present study was to evaluate the safety of ethylene glyco (EG) and 1,6-hexanediol (HD) solutions as experimental dentin primers when subjected to the guinea pig maximization test (GPMT), primary irritation test, cumulative skin irritation test and human patch test. No primary and cumulative skin irritation resulting from the use of 62.5% EG or 45% HD solutions was observed. In the case of GPMT, the animals sensitized with 2-hydroxyethyl methacrylate (2-HEMA) responded to 100% HD. 62.5% EG and 45% HD as dentin primers were safer than 2-HEMA such as a methacrylic primer. PMID:9550022

  16. Respiratory irritation associated with inhalation of boron trifluoride and fluorosulfonic acid.

    PubMed

    Rusch, George M; Bowden, Anthony M; Muijser, Hans; Arts, Josje

    2008-05-01

    The objectives of this study were to examine the respiratory irritancy of boron trifluoride (BF(3)) and fluorosulfonic acid (FSA) following acute inhalation exposure. Testing was conducted using groups of 10 male and 10 female rats (BF(3)) or groups of 6 male rats (FSA). Rats were exposed for a single 4-h period (BF(3)) or a single 1-h period (FSA) and necropsied 1 or 14 days after exposure (BF(3)) or 14 days after exposure (FSA). Measurements consisted of clinical signs, body weight, kidney and lung weight, histopathology (BF(3)), and breathing parameters (FSA) and were used to evaluate the possible irritating effects of these compounds. The results indicated treatment-related findings in the larynx and trachea in the rats exposed to 74.4 mg/m(3) BF(3), consisting of ventral cartilage necrosis, hemorrhage, and an increase in ventral epithelial hyperplasia and ventral inflammatory cell inflammation 24 h postexposure. In the animals sacrificed 14 days postexposure, the only notable observation was ventral cartilage necrosis, present in 2 animals. The next lower level tested, 24.6 mg/m(3) BF, was considered a no-observed-adverse-effects level (NOAEL). A concentration of 4125 mg/m(3) FSA resulted in a clearly decreased breathing rate during and shortly after exposure with 67% (4/6) mortality on days 5-9 after exposure. A concentration of 845 mg/m(3) FSA resulted in only minor signs of irritation, consisting of slight changes in breathing pattern shorlty after exposure. The results of the present 4-h inhalation study with BF(3) indicated that respiratory irritation was present at a level of 74.4 mg/m(3) whereas 24.6 mg/m(3) was a NOAEL. A single 1-h exposure to 845 mg/m(3) FSA resulted in only minor signs of respiratory irritation, indicating that on a mass basis FSA is no more toxic or irritating than hydrogen fluoride (HF) or sulfuric acid. PMID:18464054

  17. Protocol for a randomized controlled study of Iyengar yoga for youth with irritable bowel syndrome

    PubMed Central

    2011-01-01

    Introduction Irritable bowel syndrome affects as many as 14% of high school-aged students. Symptoms include discomfort in the abdomen, along with diarrhea and/or constipation and other gastroenterological symptoms that can significantly impact quality of life and daily functioning. Emotional stress appears to exacerbate irritable bowel syndrome symptoms suggesting that mind-body interventions reducing arousal may prove beneficial. For many sufferers, symptoms can be traced to childhood and adolescence, making the early manifestation of irritable bowel syndrome important to understand. The current study will focus on young people aged 14-26 years with irritable bowel syndrome. The study will test the potential benefits of Iyengar yoga on clinical symptoms, psychospiritual functioning and visceral sensitivity. Yoga is thought to bring physical, psychological and spiritual benefits to practitioners and has been associated with reduced stress and pain. Through its focus on restoration and use of props, Iyengar yoga is especially designed to decrease arousal and promote psychospiritual resources in physically compromised individuals. An extensive and standardized teacher-training program support Iyengar yoga's reliability and safety. It is hypothesized that yoga will be feasible with less than 20% attrition; and the yoga group will demonstrate significantly improved outcomes compared to controls, with physiological and psychospiritual mechanisms contributing to improvements. Methods/Design Sixty irritable bowel syndrome patients aged 14-26 will be randomly assigned to a standardized 6-week twice weekly Iyengar yoga group-based program or a wait-list usual care control group. The groups will be compared on the primary clinical outcomes of irritable bowel syndrome symptoms, quality of life and global improvement at post-treatment and 2-month follow-up. Secondary outcomes will include visceral pain sensitivity assessed with a standardized laboratory task (water load task

  18. Sensory and pulmonary irritation of methyl isocyanate in mice and pulmonary irritation and possible cyanidelike effects of methyl isocyanate in guinea pigs

    SciTech Connect

    Alarie, Y.; Ferguson, J.S.; Stock, M.F.; Weyel, D.A.; Schaper, M.

    1987-06-01

    Methyl isocyanate (MIC) was evaluated for sensory and pulmonary irritation in mice. MIC was found to be both a potent sensory and pulmonary irritant in this species. From these results, a safe level of exposure for a period of 8 hr was estimated to be about 0.02 ppm for humans. Guinea pigs were also exposed to MIC for a single 3-hr exposure at a concentration of 37 ppm. During exposure to MIC, coughing was observed in all animals. Pulmonary function was evaluated immediately following exposure and intermittently on the next 35 days using CO/sub 2/ challenges and flow-volume loops. Highly abnormal responses to CO/sub 2/ were observed immediately after exposure in all animals. Six of the eight animals exposed to MIC died. In the two survivors, an apparent recovery was seen during the 5 days following exposure, but a worsening effect was observed at days 21 and 28, with a partial recovery at day 35. The data clearly demonstrated that the primary pulmonary effect of MIC was one of airways obstruction. Oxygen uptake and carbon dioxide output were also measured in the guinea pigs following exposure to MIC. No evidence of a cyanidelike effect was observed, in contrast to a severe depression of oxygen uptake following exposure to hydrogen cyanide.

  19. What the MAYSI-2 Can Tell Us About Anger-Irritability and Trauma.

    PubMed

    McCoy, Henrika; Leverso, John; Bowen, Elizabeth A

    2016-04-01

    The rate of experiencing trauma can be quite high for juvenile offenders and those experiences can lead to feelings of anger and irritability. This study uses Massachusetts Youth Screening Instrument-Version 2 (MAYSI-2) data to examine the relationship between the Traumatic Experiences (TE) and Angry-Irritable (AI) scales for juvenile offenders (N = 1,348) from a Midwest detention center. Chi-square analyses revealed statistically significant relationships between the AI scale and gender, race, and the TE scale. In addition, ordinal logistic regression results showed that as the number of traumatic experiences increased, so did the odds of scoring Caution or Warning on the AI scale. Recommendations are that juvenile justice systems utilize a trauma-informed process throughout the adjudicatory process and there be improved efforts to coordinate services across multiple systems, such as child welfare and special education, where juvenile offenders are often engaged. PMID:25395475

  20. Thromboxane synthetase inhibition reduces ventricular irritability after coronary occlusion and reperfusion.

    PubMed

    Austin, J C; Berrizbeitia, L D; Schoen, F J; Kauffman, R P; Hechtman, H B; Cohn, L H

    1988-03-01

    Reperfusion of ischemic tissue is responsible for production of metabolites with deleterious local vascular effects. Thromboxane A2, a potent vasoconstrictor and platelet aggregator, has been implicated as a mediator of the "reperfusion injury." We studied the effect of an experimental thromboxane synthetase inhibitor, OKY-046, on coronary sinus thromboxane levels, ventricular irritability, myocardial contractility, infarct salvage, and histologic features of reperfusion. Sixteen sheep were randomized to OKY-046, 3 mg/kg, or saline vehicle before 3-hour occlusion and subsequent reperfusion of the left anterior descending artery. The OKY group demonstrated less ventricular irritability as measured by incidence of ventricular fibrillation and necessity for countershock to reverse tachyarrhythmias. Coronary sinus thromboxane levels were significantly lower in the OKY group compared with the control group. There is additional evidence to suggest that OKY increases infarct salvage and attenuates histologic features of microcirculatory damage. PMID:3344655

  1. Retinoids activate the irritant receptor TRPV1 and produce sensory hypersensitivity.

    PubMed

    Yin, Shijin; Luo, Jialie; Qian, Aihua; Du, Junhui; Yang, Qing; Zhou, Shentai; Yu, Weihua; Du, Guangwei; Clark, Richard B; Walters, Edgar T; Carlton, Susan M; Hu, Hongzhen

    2013-09-01

    Retinoids are structurally related derivatives of vitamin A and are required for normal vision as well as cell proliferation and differentiation. Clinically, retinoids are effective in treating many skin disorders and cancers. Application of retinoids evokes substantial irritating side effects, including pain and inflammation; however, the precise mechanisms accounting for the sensory hypersensitivity are not understood. Here we show that both naturally occurring and synthetic retinoids activate recombinant or native transient receptor potential channel vanilloid subtype 1 (TRPV1), an irritant receptor for capsaicin, the pungent ingredient of chili peppers. In vivo, retinoids produced pain-related behaviors that were either eliminated or significantly reduced by genetic or pharmacological inhibition of TRPV1 function. These findings identify TRPV1 as an ionotropic receptor for retinoids and provide cellular and molecular insights into retinoid-evoked hypersensitivity. These findings also suggest that selective TRPV1 antagonists are potential therapeutic drugs for treating retinoid-induced sensory hypersensitivity. PMID:23925292

  2. Neurobehavioral and sensory irritant effects of controlled exposure to a complex mixture of volatile organic compounds

    SciTech Connect

    Otto, D.; Molhave, L.; Rose, G.; Hudnell, H.K.; House, D. )

    1990-11-01

    Subjective reactions of discomfort, impaired air quality, irritation of mucosal membranes, and impaired memory have been reported in chemically sensitive subjects during exposure to volatile organic compounds (VOCs) found in new buildings. Sixty-six normal healthy male subjects aged 18-39 were exposed for 2.75 hr to a complex VOC mixture at 0 and 25 mg/m3. Each subject completed control and exposure sessions at one-week intervals in counterbalanced order. Measurements included comfort ratings of eye, nose and throat irritation, symptom questionnaire and computerized behavioral tests. Subjects found the odor of VOCs unpleasantly strong and reported that VOC exposure degraded air quality, increased headache and produced general discomfort. VOC exposure did not affect performance on any behavioral tests.

  3. Elemental changes at irritant reactions due to chromate and nickel in guinea-pig epidermis

    SciTech Connect

    Lindberg, M.; Forslind, B.; Roomans, G.M.

    1983-01-01

    The present investigation was performed to examine the possibility of using energy dispersive X-ray microanalysis (EDX) to obtain information on epidermal reactions at irritant dermatitis. The elemental redistribution in the stratum germinativum and stratum spinosum of the guinea-pig epidermis after intradermal injection of a chromate and a nickel solution was studied in thick cryo-sections. The two solutions caused different changes in elemental content in both cell layers. Nickel sulfate caused a conspicuous decrease in K levels whereas Na and Cl were elevated in both cell layers. Potassium chromate caused an increase in Cl but lowered the P values. The result of this study show that it is possible to use EDX-analysis of thick skin sections to obtain information on physiologically relevant alterations in epidermis at irritant dermatitis.

  4. Comparative pathology of the nasal mucosa in laboratory animals exposed to inhaled irritants

    SciTech Connect

    Harkema, J.R. )

    1990-04-01

    The nasal cavity is susceptible to chemically induced injury as a result of exposure to inhaled irritants. Some responses of the nasal mucosa to inhaled toxicants are species specific. These species-related differences in response may be due to variations in structural, physiologic, and biochemical factors, such as gross nasal cavity structure, distribution of luminal epithelial cell populations along the nasal airway, intranasal airflow patterns, nasal mucociliary apparatus, and nasal xenobiotic metabolism among animal species. This paper reviews the comparative anatomy and irritant-induced pathology of the nasal cavity in laboratory animals. The toxicologist, pathologist, and environmental risk assessor must have a good working knowledge of the similarities and differences in normal nasal structure and response to injury among species before they can select animal models for nasal toxicity studies, recognize toxicant-induced lesions in the nasal airway, and extrapolate experimental results to estimate the possible effects of an inhaled toxicant on the human nasal airway.

  5. Bowel function and irritable bowel symptoms after hysterectomy and cholecystectomy--a population based study.

    PubMed Central

    Heaton, K W; Parker, D; Cripps, H

    1993-01-01

    Because unsubstantiated beliefs link hysterectomy and cholecystectomy with bowel function, this study examined all the women who had had these operations in a defined population (79 and 37 respectively, out of 1058) with respect to bowel habits, irritable bowel syndrome symptoms, and whole gut transit time calculated from records of three defecations. Compared with unoperated controls, women after hysterectomy were more likely to consider themselves constipated; they also strained more and admitted more often to bloating and feelings of incomplete evacuation. Their stools tended to be lumpier and, in women over 50 years, transit time was longer. When women treated by cholecystectomy were compared with women having newly discovered, asymptomatic gall stones, they more often described defecation as urgent but had no other detectable differences. In conclusion symptomatic constipation is frequent in women after hysterectomy; after cholecystectomy, bowel habit is not consistently changed but the rectum seems to be more irritable. PMID:8174964

  6. Medical Movies on the Web Debuts with Gene Kelly's "Combat Fatigue Irritability" 1945 Film | NIH MedlinePlus the ...

    MedlinePlus

    ... please turn JavaScript on. Medical Movies on the Web Debuts with Gene Kelly's "Combat Fatigue Irritability" 1945 ... of Medicine To view Medical Movies on the Web, go to: www.nlm.nih.gov/hmd/collections/ ...

  7. Food allergy in irritable bowel syndrome: new facts and old fallacies

    PubMed Central

    Isolauri, E; Rautava, S; Kalliomäki, M

    2004-01-01

    The notion of food allergy in irritable bowel syndrome (IBS) is not new. However, recent evidence suggests significant reduction in IBS symptom severity in patients on elimination diets, provided that dietary elimination is based on foods against which the individual had raised IgG antibodies. These findings should encourage studies dissecting the mechanisms responsible for IgG production against dietary antigens and their putative role in IBS PMID:15361481

  8. Contact Irritant Responses of Aedes aegypti Using Sublethal Concentration and Focal Application of Pyrethroid Chemicals

    PubMed Central

    Manda, Hortance; Shah, Pankhil; Polsomboon, Suppaluck; Chareonviriyaphap, Theeraphap; Castro-Llanos, Fanny; Morrison, Amy; Burrus, Roxanne G.; Grieco, John P.; Achee, Nicole L.

    2013-01-01

    Background Previous studies have demonstrated contact irritant and spatial repellent behaviors in Aedes aegypti following exposure to sublethal concentrations of chemicals. These sublethal actions are currently being evaluated in the development of a push-pull strategy for Ae. aegypti control. This study reports on mosquito escape responses after exposure to candidate chemicals for a contact irritant focused push-pull strategy using varying concentrations and focal application. Methods Contact irritancy (escape) behavior, knockdown and 24 hour mortality rates were quantified in populations of female Ae. aegypti under laboratory conditions and validated in the field (Thailand and Peru) using experimental huts. Evaluations were conducted using varying concentrations and treatment surface area coverage (SAC) of three pyrethroid insecticides: alphacypermethrin, lambacyhalothrin and deltamethrin. Results Under laboratory conditions, exposure of Ae. aegypti to alphacypermethrin using the standard field application rate (FAR) resulted in escape responses at 25% and 50% SAC that were comparable with escape responses at 100% SAC. Significant escape responses were also observed at <100% SAC using ½FAR of all test compounds. In most trials, KD and 24 hour mortality rates were higher in mosquitoes that did not escape than in those that escaped. In Thailand, field validation studies indicated an early time of exit (by four hours) and 40% increase in escape using ½FAR of alphacypermethrin at 75% SAC compared to a matched chemical-free control. In Peru, however, the maximum increase in Ae. aegypti escape from alphacypermethrin-treated huts was 11%. Conclusions/Significance Results presented here suggest a potential role for sublethal and focal application of contact irritant chemicals in an Ae. aegypti push-pull strategy to reduce human–vector contact inside treated homes. However, the impact of an increase in escape response on dengue virus transmission is currently unknown

  9. Resident Rounds: Part III - Case Report: Betel Quid Induced Irritant Contact Dermatitis of the Hand.

    PubMed

    Mathieu, Regine J; Cheraghi, Nikoo; Russo, Marian A

    2016-06-01

    Betel quid is a drug used in Far East Asia, India, and the South Pacific. The habit of betel quid chewing is widely reported to cause oral cancer and tooth and gum disease. However, skin disease due to betel quid use is underreported. We report a case of irritant contact dermatitis to betel quid components in a 35-year-old male betel quid user who presented for evaluation of a persistent rash on his fingertips. PMID:27272092

  10. Betaine reduces the irritating effect of sodium lauryl sulfate on human oral mucosa in vivo.

    PubMed

    Rantanen, Irma; Nicander, Ingrid; Jutila, Kirsti; Ollmar, Stig; Tenovuo, Jorma; Söderling, Eva

    2002-10-01

    Our aim was to evaluate whether betaine has a protective effect during exposure of the human oral mucosa in vivo to sodium lauryl sulfate (SLS) or cocoamidopropylbetaine (CAPB) as measured with a multifrequency electrical impedance spectrometer (EI). Both detergents were used at the concentration of 2.0% w/v with and without 4.0% w/v betaine in distilled water in 20 volunteers, and 0.5% and 1.0% w/v SLS combined with 4.0% w/v betaine in 5 volunteers. EI measurements were taken before application of the test solutions, after their removal, and every 15 min up to 45 min. Both 0.5% and 1% SLS solutions showed a significant reduction in 3 of the 4 indices, indicating mucosal irritation after the 15-min exposure (P < 0.05), whereas 2% SLS did so in all 4 indices (P < 0.001). Betaine had no effect on the detergent-induced decline with either the 2% or the 0.5% SLS solutions. However, when combined with the 1% SLS solution, betaine significantly (P < 0.05) reduced mucosal irritation by abolishing decreases in indices MIX (magnitude index) and IMIX (imaginary part index) and lowering it for PIX (phase index). The 2% CAPB solution showed a significant (P < 0.05) reduction in all 4 indices after the 15-min exposure, but the effect was significantly weaker than that of 2% SLS (P < 0.05). Betaine did not reduce the irritating effect of 2% CAPB. These findings can be used in the development of less irritating products for oral health care. PMID:12418722

  11. Classification of sensitizing and irritative potential in a combined in-vitro assay

    SciTech Connect

    Wanner, Reinhard; Sonnenburg, Anna; Quatchadze, Maria; Schreiner, Maximilian; Peiser, Matthias; Zuberbier, Torsten; Stahlmann, Ralf

    2010-06-01

    We have developed a coculture system which in parallel indicates the sensitizing and irritative potential of xenobiotics. The assay is named loose-fit coculture-based sensitization assay (LCSA) and may be performed within 5 days. The system is composed of human monocytes that differentiate to a kind of dendritic cells by 2-day culturing in the presence of allogenic keratinocytes. The culture medium is enriched by a cocktail of recombinant cytokines. On day 3, concentration series of probes are added. On day 5, cells are harvested and analyzed for expression range of CD86 as a marker of sensitizing potential and for uptake of the viability stain 7-AAD as a marker of irritative potential. Estimation of the concentration required to cause a half-maximal increase in CD86 expression allowed quantification of sensitizing potential, and estimation of the concentration required to reduce viability to 50% allowed quantification of irritative potential. Examination of substances with known potential resulted in categorization of test scores. To evaluate our data, we have compared results with those of the validated animal-based sensitization test, the murine local lymph node assay (LLNA, OECD TG 429). To a large extent, results from LCSA and from LLNA achieved analogous grouping of allergens into categories like weak-moderate-strong. However, the new assay showed an improved capacity to distinguish sensitizers from non-sensitizers and irritants. In conclusion, the LCSA contains potential to fulfil the requirements of the EU's programme for the safety of chemicals 'Registration, Evaluation, Authorisation and Restriction of chemical substances' (REACH, 2006) to replace animal models.

  12. Quantitative Risk-Benefit Analysis of Probiotic Use for Irritable Bowel Syndrome and Inflammatory Bowel Disease.

    PubMed

    Bennett, William E

    2016-04-01

    Probiotics have seen widespread use for a variety of gastrointestinal problems, especially in two common disorders: irritable bowel syndrome and inflammatory bowel disease. Since a wide variety of probiotic preparations has been used, and despite a large number of studies performed, a great deal of heterogeneity exists among them. Straightforward evidence-based recommendations for the use of probiotics in irritable bowel syndrome and inflammatory bowel disease have thus been difficult to formulate. In an effort to improve understanding of the risk-benefit balance of probiotics in these conditions, this study (1) queried the US FDA Adverse Event Reporting System (FAERS) database for all reported adverse drug events related to probiotics in 2013, and (2) constructed risk-benefit planes for both irritable bowel syndrome and inflammatory bowel disease using a geometric approximation of the confidence region between risk and benefit. The results show that adverse events from probiotics vary widely by disease, and when they occur, they are mild and may be difficult to distinguish from the natural history of the underlying disorders they are used to treat. The risk-benefit plane for irritable bowel syndrome straddles the risk-benefit threshold, so patients can expect a balance between a low chance of risk and also a low chance of benefit. The risk-benefit plane for inflammatory bowel disease largely lies above the risk-benefit threshold, so patients may expect more benefit than risk in most cases. More standardized and high-quality research is needed to improve our understanding of risk and benefit for these complex biopharmaceuticals. PMID:26467550

  13. [Effectiveness of pharmacotherapy of irritated bowel syndrome from the standpoint of evidence based medicine].

    PubMed

    Sheptulin, A A; Vize-Khripunova, M A

    2014-01-01

    Evaluation of the action of various medicines used to treat irritated bowel syndrome from the standpoint of evidence based medicine indicates that most of them (spasmolytics, probiotics, loperamide, aperients) show but low effectiveness. The use of more efficacious preparations (alosterone, cisapride, tegacerode) is associated with serious adverse reactions whereas prucalopride is applied for unregistered indications. It necessitates the development of new drugs with enhanced effectiveness and tolerability. PMID:25775909

  14. Standardized hypnosis treatment for irritable bowel syndrome: the North Carolina protocol.

    PubMed

    Palsson, Olafur S

    2006-01-01

    The North Carolina protocol is a seven-session hypnosis-treatment approach for irritable bowel syndrome that is unique in that the entire course of treatment is designed for verbatim delivery. The protocol has been tested in two published research studies and found to benefit more than 80% of patients. This article describes the development, content, and testing of the protocol, and how it is used in clinical practice. PMID:16316883

  15. Transrectal ultrasonography: relationship with anorectal manometry, electromyography and sensitivity tests in irritable bowel syndrome.

    PubMed

    Awad, R A; Martin, J; Cal y Major, M; Noguera, J L; Ramos, R; Amezcua, C; Camacho, S; Santiago, R; Ramirez, J L; Castro, J

    1998-01-01

    Irritable bowel syndrome is the most frequently diagnosed disorder in gastroenterology. It has been demonstrated with specialized motility studies that these patients compared to healthy subjects show changes in rectoanal electrical and mechanical activity and in rectoanal sensitivity. However, until now no report has been published on morphological alterations in the rectum or the internal anal sphincter. Twenty-five consecutive patients with irritable bowel syndrome (mean age 32, range 17-47 years; 24 females) were evaluated prospectively by transrectal ultrasonography, rectal sensitivity studies, and recordings of both electrical and mechanical activity of the distal rectum and internal anal sphincter during a 2-h inter-digestive period. Ten healthy volunteers (mean age 34.5, range 19-50 years) served as a control group. Paired and non-paired Student's two-tailed t test and linear regression analysis were used. It was shown that muscle thickness of the rectum during rest (4.7 +/- 0.1 mm) was correlated neither with its rectal spike amplitude (0.73 +/- 0.1 mV) nor with rectal spike frequency (17.06 +/- 3.6 spike/2 h). In addition, the diameter of the internal anal sphincter (1.2 +/- 0.1 mm) was correlated neither with its resting pressure, nor with frequency (17.1 +/- 3.2/2 h), duration (14.9 +/- 1.5 s), or amplitude (14.1 +/- 1.9 mmHg), of inhibition of the spontaneous rectoanal inhibitory reflex. No correlation was found between ultrasonographic parameters and rectal distension variables (r = 0.03). This study demonstrates for the first time morphological anorectal changes in patients with irritable bowel syndrome compared to healthy subjects, in addition to showing that morphological changes are independent of physiological ones. Therefore both transrectal ultrasonography to determine anorectal morphology and electromanometry to assess anorectal function are important measures in the evaluation of patients with irritable bowel syndrome. PMID:9638493

  16. Role of pinaverium bromide in south Indian patients with irritable bowel syndrome.

    PubMed

    Jayanthi, V; Malathi, S; Ramathilakam, B; Dinakaran, N; Balasubramanian, V; Mathew, S

    1998-04-01

    The effect of pinaverium bromide in controlling gastrointestinal symptoms in 61 patients with irritable bowel syndrome was studied, as an open trial. Individually, there was significant relief in abdominal discomfort/pain as well as in bowel symptoms in most of the patients. Abdominal pain was reduced in 49%, stool consistency improved in 74%, straining and urgency decreased in 71% and mucus decreased in 64%. Tolerance to the drug administered was good and side-effects reported were few. PMID:11273320

  17. Development of Organogel-Derived Capsaicin Nanoemulsion with Improved Bioaccessibility and Reduced Gastric Mucosa Irritation.

    PubMed

    Lu, Muwen; Cao, Yong; Ho, Chi-Tang; Huang, Qingrong

    2016-06-15

    Capsaicin (CAP) is the major active component in chili peppers with health-promoting benefits. However, the low bioavailability and irritating quality of CAP greatly limit its applications in functional foods. The objective of this study was to develop a food-grade nanoemulsion to increase the dissolution and bioaccessibility of CAP and to alleviate its irritating effects. To achieve this goal, CAP was first dissolved in medium-chain triacylglycerol (MCT), followed by the addition of sucrose stearate S-370 as organogelator to develop CAP-loaded organogel. The oil-in-water (O/W) emulsion was formed using organogel as the oil phase and Tween 80 as the emulsifier. After ultrasonication treatment, droplet sizes of emulsion were decreased to 168 nm with enhanced dissolution rate and bioaccessibility. In vivo study further confirmed the reduced rat gastric mucosa irritation caused by CAP. The organogel-derived nanoemulsion was proved to be an effective delivery system for CAP-based functional food products. PMID:27170269

  18. Remote Subcutaneous Needling to Suppress the Irritability of Myofascial Trigger Spots: An Experimental Study in Rabbits

    PubMed Central

    Fu, Zhonghua; Hsieh, Yueh-Ling; Hong, Chang-Zern; Kao, Mu-Jung; Lin, Jaung-Geng; Chou, Li-Wei

    2012-01-01

    Objective. To obtain electrophysiological effects of Fu's subcutaneous needling (FSN) on needling distance by assessment of endplate noise (EPN) recorded from the myofascial trigger spots (MTrSs) in rabbit skeletal muscle. Method. Eighteen New Zealand rabbits weighing 2.5–3.0 kg were randomly divided into two groups as follows: proximal needling (PN) group and distal needling (DN) group. The needling procedure followed the instructions described by the inventor of FSN, including needling insertion and swaying movement. The amplitudes of EPN on the MTrS region of BF muscle were recorded as an index of MTrS irritability. Random sampling of EPN tracings were taken for further analyses before, during, and after FSN treatment. Results. In PN and DN groups, the trends of EPN amplitude alterations were similar at conditions before, during, and after FSN treatment. The degree of reduction in the EPN amplitude in PN group was significantly higher than that in DN group. There were no significant changes in EPN amplitudes in the MTrS of contralateral BF without FSN intervention either in DN or PN group. Conclusion. The irritability of proximal MTrSs could be modulated after ipsilateral FSNs. The placement of FSN may affect the effectiveness of suppression of irritability of MTrSs. PMID:23346200

  19. Irritant activation of epithelial cells is mediated via protease-dependent EGFR activation.

    PubMed

    White, Kellie J; Maffei, Vincent J; Newton-West, Marvin; Swerlick, Robert A

    2011-02-01

    Although numerous studies have examined in vivo and in vitro effects of irritants, most focused on events developing hours to days after exposure. Molecular events occurring immediately after skin contact remain incompletely defined. Characterization of early events could lead to the identification of key molecular signals necessary for the production of inflammatory mediators responsible for the signs and symptoms of irritant contact dermatitis (ICD). HaCaT cells treated with sodium lauryl sulfate (SLS), a model irritant, were used to examine early molecular events of ICD. Western analysis showed SLS-mediated induction of early growth response-1 (egr-1), a transcription factor capable of regulating hallmarks of ICD such as angiogenesis, hyperproliferation, and inflammation. Additionally, de novo egr-1 expression was commensurate with transcriptional activation of egr-1 mRNA and heteronuclear RNA. Use of pharmacological inhibitors demonstrated that SLS-induced egr-1 was dependent on MEK1/p44/42 ERK, but not on p38 or JNK signaling. The EGFR inhibitor PD168393 and the metalloprotease inhibitor TAPI-2 both inhibited SLS-induced egr-1. Finally, small interfering RNA silencing of the EGFR diminished SLS-induced egr-1 mRNA. These studies suggest a role of the EGFR in SLS signaling as well as a, to our knowledge, previously unreported association between ICD and EGFR induction of egr-1. PMID:20981109

  20. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents.

    PubMed

    Bautista, Diana M; Jordt, Sven-Eric; Nikai, Tetsuro; Tsuruda, Pamela R; Read, Andrew J; Poblete, Jeannie; Yamoah, Ebenezer N; Basbaum, Allan I; Julius, David

    2006-03-24

    TRPA1 is an excitatory ion channel targeted by pungent irritants from mustard and garlic. TRPA1 has been proposed to function in diverse sensory processes, including thermal (cold) nociception, hearing, and inflammatory pain. Using TRPA1-deficient mice, we now show that this channel is the sole target through which mustard oil and garlic activate primary afferent nociceptors to produce inflammatory pain. TRPA1 is also targeted by environmental irritants, such as acrolein, that account for toxic and inflammatory actions of tear gas, vehicle exhaust, and metabolic byproducts of chemotherapeutic agents. TRPA1-deficient mice display normal cold sensitivity and unimpaired auditory function, suggesting that this channel is not required for the initial detection of noxious cold or sound. However, TRPA1-deficient mice exhibit pronounced deficits in bradykinin-evoked nociceptor excitation and pain hypersensitivity. Thus, TRPA1 is an important component of the transduction machinery through which environmental irritants and endogenous proalgesic agents depolarize nociceptors to elicit inflammatory pain. PMID:16564016

  1. THE INTESTINAL MICROBIOTA AND THE ROLE OF PROBIOTICS IN IRRITABLE BOWEL SYNDROME: a review.

    PubMed

    Moraes-Filho, Joaquim Prado; Quigley, Eamonn M M

    2015-12-01

    Irritable bowel syndrome is a common, chronic relapsing gastrointestinal disorder that affects 7%-22% of the population worldwide. According to Rome III Criteria, the disorder is defined by the coexistence of abdominal discomfort or pain associated with an alteration in bowel habits. Its pathophysiology is not completely understood but, in addition to some important abnormalities, the disturbed intestinal microbiota has also been described supported by several strands of evidence. The treatment of irritable bowel syndrome is based upon several therapeutic approaches but few have been successful or without adverse events and more recently the gut microbiota and the use of probiotics have emerged as a factor to be considered. Probiotics are live micro-organisms which when consumed in adequate amounts confer a health benefit to the host, such as Lactic bacteria among others. An important scientific rationale has emerged for the use of probiotics in irritable bowel syndrome, although the data regarding different species are still limited. Not all probiotics are beneficial: it is important to select the specific strain which should be supported by good evidence base. The mechanisms of action of probiotics are described and the main strains are quoted. PMID:26840477

  2. Effect of mixing conditions on irritant potency of zinc oxide and sulfur dioxide. [Guinea pigs

    SciTech Connect

    Amdur, M.O.; McCarthy, J.F.; Gill, M.W.

    1983-01-01

    Measurement of mechanics of respiration in guinea pigs was used to assess the irritant potency of zinc oxide and sulfur dioxide mixed under different conditions of temperature and humidity. Concentrations were 1-2 mg/m/sup 3/ zinc oxide and 1 ppm sulfur dioxide. Dry conditions of mixing (Chamber RH 30%) either at 24/sup 0/C in the exposure chamber or at 480/sup 0/C in a dry furnace gave a biological response which could be completely accounted for by responses to zinc oxide and/or sulfur dioxide alone. Chemical examination of the aerosols did not indicate the formation of particulate sulfur species. Zinc oxide and sulfur dioxide mixed dry at 480/sup 0/C and fed into the exposure chamber at 80% RH reacted to produce an irritant aerosol as evidenced by a rapid increase in resistance to levels 29% above control; reversal was rapid when exposure ended. Chemical studies indicated the presence of sulfite on these aerosols. Addition of water vapor to the furnace during mixing at 480/sup 0/C produced a different irritant aerosol. The resistance rose slowly to 19% above control values and remained elevated during the post-exposure hour. Chemical studies indicated the presence of sulfate, sulfite, and adsorbed sulfur trioxide on these aerosols.

  3. Investigation of the Dermal Absorption and Irritation Potential of Sertaconazole Nitrate Anhydrous Gel.

    PubMed

    Manian, Mahima; Madrasi, Kumpal; Chaturvedula, Ayyappa; Banga, Ajay K

    2016-01-01

    Effective topical therapy of cutaneous fungal diseases requires the delivery of the active agent to the target site in adequate concentrations to produce a pharmacological effect and inhibit the growth of the pathogen. In addition, it is important to determine the concentration of the drug in the skin in order to evaluate the subsequent efficacy and potential toxicity for topical formulations. For this purpose, an anhydrous gel containing sertaconazole nitrate as a model drug was formulated and the amount of the drug in the skin was determined by in vitro tape stripping. The apparent diffusivity and partition coefficients were then calculated by a mathematical model describing the dermal absorption as passive diffusion through a pseudo-homogenous membrane. The skin irritation potential of the formulation was also assessed by using the in vitro Epiderm™ model. An estimation of the dermal absorption parameters allowed us to evaluate drug transport across the stratum corneum following topical application. The estimated concentration for the formulation was found to be higher than the MIC100 at the target site which suggested its potential efficacy for treating fungal infections. The skin irritation test showed the formulation to be non-irritating in nature. Thus, in vitro techniques can be used for laying the groundwork in developing efficient and non-toxic topical products. PMID:27399763

  4. A Preliminary Study of White Matter in Adolescent Depression: Relationships with Illness Severity, Anhedonia, and Irritability

    PubMed Central

    Henderson, Sarah E.; Johnson, Amy R.; Vallejo, Ana I.; Katz, Lev; Wong, Edmund; Gabbay, Vilma

    2013-01-01

    Major depressive disorder (MDD) during adolescence is a common and disabling psychiatric condition; yet, little is known about its neurobiological underpinning. Evidence indicates that MDD in adults involves alterations in white and gray matter; however, sparse research has focused on adolescent MDD. Similarly, little research has accounted for the wide variability of symptom severity among depressed teens. Here, we aimed to investigate white matter (WM) microstructure between 17 adolescents with MDD and 16 matched healthy controls (HC) using diffusion tensor imaging. We further assessed within the MDD group relationships between WM integrity and depression severity, as well as anhedonia and irritability – two core symptoms of adolescent MDD. As expected, adolescents with MDD manifested decreased WM integrity compared to HC in the anterior cingulum and anterior corona radiata. Within the MDD group, greater depression severity was correlated with reduced WM integrity in the genu of corpus callosum, anterior thalamic radiation, anterior cingulum, and sagittal stratum. However, anhedonia and irritability were associated with alterations in distinct WM tracts. Specifically, anhedonia was associated with disturbances in tracts related to reward processing, including the anterior limb of the internal capsule and projection fibers to the orbitofrontal cortex. Irritability was associated with decreased integrity in the sagittal stratum, anterior corona radiata, and tracts leading to prefrontal and temporal cortices. Overall, these preliminary findings provide further support for the hypotheses that there is a disconnect between prefrontal and limbic emotional regions in depression, and that specific clinical symptoms involve distinct alterations in WM tracts. PMID:24324445

  5. A preliminary study of white matter in adolescent depression: relationships with illness severity, anhedonia, and irritability.

    PubMed

    Henderson, Sarah E; Johnson, Amy R; Vallejo, Ana I; Katz, Lev; Wong, Edmund; Gabbay, Vilma

    2013-01-01

    Major depressive disorder (MDD) during adolescence is a common and disabling psychiatric condition; yet, little is known about its neurobiological underpinning. Evidence indicates that MDD in adults involves alterations in white and gray matter; however, sparse research has focused on adolescent MDD. Similarly, little research has accounted for the wide variability of symptom severity among depressed teens. Here, we aimed to investigate white matter (WM) microstructure between 17 adolescents with MDD and 16 matched healthy controls (HC) using diffusion tensor imaging. We further assessed within the MDD group relationships between WM integrity and depression severity, as well as anhedonia and irritability - two core symptoms of adolescent MDD. As expected, adolescents with MDD manifested decreased WM integrity compared to HC in the anterior cingulum and anterior corona radiata. Within the MDD group, greater depression severity was correlated with reduced WM integrity in the genu of corpus callosum, anterior thalamic radiation, anterior cingulum, and sagittal stratum. However, anhedonia and irritability were associated with alterations in distinct WM tracts. Specifically, anhedonia was associated with disturbances in tracts related to reward processing, including the anterior limb of the internal capsule and projection fibers to the orbitofrontal cortex. Irritability was associated with decreased integrity in the sagittal stratum, anterior corona radiata, and tracts leading to prefrontal and temporal cortices. Overall, these preliminary findings provide further support for the hypotheses that there is a disconnect between prefrontal and limbic emotional regions in depression, and that specific clinical symptoms involve distinct alterations in WM tracts. PMID:24324445

  6. Analysis of Draize eye irritation testing and its prediction by mining publicly available 2008-2014 REACH data.

    PubMed

    Luechtefeld, Thomas; Maertens, Alexandra; Russo, Daniel P; Rovida, Costanza; Zhu, Hao; Hartung, Thomas

    2016-01-01

    Public data from ECHA online dossiers on 9,801 substances encompassing 326,749 experimental key studies and additional information on classification and labeling were made computable. Eye irritation hazard, for which the rabbit Draize eye test still represents the reference method, was analyzed. Dossiers contained 9,782 Draize eye studies on 3,420 unique substances, indicating frequent retesting of substances. This allowed assessment of the test's reproducibility test based on all substances tested more than once. There was a 10% chance of a non-irritant evaluation given after a prior severe-irritant result as given by UN GHS classification criteria. The most reproducible outcomes were the results negative (94% reproducible) and severe eye irritant (73% reproducible). To evaluate whether other GHS categorizations predict eye irritation we built a dataset of 5,629 substances (1,931 'irritant' and 3,698 'non-irritant'). The two best decision trees with up to three other GHS classifications resulted in balanced accuracies of 68% and 73%, i.e., in the rank order of the Draize rabbit eye test itself, but both use inhalation toxicity data ("May cause respiratory irritation"), which is not typically available. Next, a dataset of 929 substances with at least one Draize study was mapped to PubChem to compute chemical similarity using 2D conformational fingerprints and Tanimoto similarity. Using a minimum similarity of 0.7 and simple classification by the closest chemical neighbor resulted in balanced accuracy from 73% over 737 substances to 100% at a threshold of 0.975 over 41 substances. This represents a strong support of read-across and (Q)SAR approaches in this area. PMID:26863293

  7. Second-phase validation study of short time exposure test for assessment of eye irritation potency of chemicals.

    PubMed

    Kojima, Hajime; Hayashi, Kazuhiko; Sakaguchi, Hitoshi; Omori, Takashi; Otoizumi, Takuya; Sozu, Takashi; Kuwahara, Hirofumi; Hayashi, Takumi; Sakaguchi, Mayumi; Toyoda, Akemi; Goto, Haruka; Watanabe, Shinichi; Ahiko, Kyoko; Nakamura, Tsuneaki; Morimoto, Takashi

    2013-09-01

    A Short Time Exposure (STE) test is a cytotoxicity test that uses SIRC cells (rabbit corneal cell line) to assess eye irritation potency following a 5-min chemical exposure. This second-phase validation study assessed the predictive capacity of the STE test using 40 coded test substances at three laboratories. A Validation Management Team (VMT) then evaluated the predictivity of the STE test for United Nation (UN) Globally Harmonized System (GHS) categories using 63 test substances including the results of the first-phase validation study. The STE test can assess not only the severe or corrosive ocular irritants (corresponding to the UN GHS Category 1) but also non-irritant (corresponding to UN GHS Non Category) from other toxicity classes, especially for limited types of test substances. The predictivity by STE test, however, was insufficient for identification of UN GHS categories (Category 1, Category 2, or Non Category). These results suggest that the STE test can be recommended as an initial step in a top-down approach to identification of severe irritants and test substances that require classification for eye irritation (UN GHS Category 1) as well as an initial step in a bottom-up approach to identification of test substances that do not require classification for eye irritation (UN GHS Non Category) from other toxicity classes, especially for limited types of test substances. On the other hand, the STE test is not considered adequate for the identification of mild or moderate irritants (i.e., UN GHS Categories 2A and 2B) and severe irritants (UN GHS Category 1). PMID:23747838

  8. Validation study of the in vitro skin irritation test with the LabCyte EPI-MODEL24.

    PubMed

    Kojima, Hajime; Ando, Yoko; Idehara, Kenji; Katoh, Masakazu; Kosaka, Tadashi; Miyaoka, Etsuyoshi; Shinoda, Shinsuke; Suzuki, Tamie; Yamaguchi, Yoshihiro; Yoshimura, Isao; Yuasa, Atsuko; Watanabe, Yukihiko; Omori, Takashi

    2012-03-01

    A validation study on an in vitro skin irritation assay was performed with the reconstructed human epidermis (RhE) LabCyte EPI-MODEL24, developed by Japan Tissue Engineering Co. Ltd (Gamagori, Japan). The protocol that was followed in the current study was an optimised version of the EpiSkin protocol (LabCyte assay). According to the United Nations Globally Harmonised System (UN GHS) of classification for assessing the skin irritation potential of a chemical, 12 irritants and 13 non-irritants were validated by a minimum of six laboratories from the Japanese Society for Alternatives to Animal Experiments (JSAAE) skin irritation assay validation study management team (VMT). The 25 chemicals were listed in the European Centre for the Validation of Alternative Methods (ECVAM) performance standards. The reconstructed tissues were exposed to the chemicals for 15 minutes and incubated for 42 hours in fresh culture medium. Subsequently, the level of interleukin-1 alpha (IL-1 α) present in the conditioned medium was measured, and tissue viability was assessed by using the MTT assay. The results of the MTT assay obtained with the LabCyte EPI-MODEL24 (LabCyte MTT assay) demonstrated high within-laboratory and between-laboratory reproducibility, as well as high accuracy for use as a stand-alone assay to distinguish skin irritants from non-irritants. In addition, the IL-1α release measurements in the LabCyte assay were clearly unnecessary for the success of this model in the classification of chemicals for skin irritation potential. PMID:22558976

  9. Effectiveness of trimebutine maleate on modulating intestinal hypercontractility in a mouse model of postinfectious irritable bowel syndrome.

    PubMed

    Long, Yanqin; Liu, Ying; Tong, Jingjing; Qian, Wei; Hou, Xiaohua

    2010-06-25

    Trimebutine maleate, which modulates the calcium and potassium channels, relieves abdominal pain in patients with irritable bowel syndrome. However, its effect on postinfectious irritable bowel syndrome is not clarified. The aim of this study was to investigate the effectiveness of trimebutine maleate on modulating colonic hypercontractility in a mouse model of postinfectious irritable bowel syndrome. Mice infected up to 8 weeks with T. spiralis underwent abdominal withdrawal reflex to colorectal distention to evaluate the visceral sensitivity at different time points. Tissues were examined for histopathology scores. Colonic longitudinal muscle strips were prepared in the organ bath under basal condition or to be stimulated by acetylcholine and potassium chloride, and consecutive concentrations of trimebutine maleate were added to the bath to record the strip responses. Significant inflammation was observed in the intestines of the mice infected 2 weeks, and it resolved in 8 weeks after infection. Visceral hyperalgesia and colonic muscle hypercontractility emerged after infection, and trimebutine maleate could effectively reduce the colonic hyperreactivity. Hypercontractility of the colonic muscle stimulated by acetylcholine and high K(+) could be inhibited by trimebutine maleate in solution with Ca(2+), but not in Ca(2+) free solution. Compared with 8-week postinfectious irritable bowel syndrome group, 2-week acute infected strips were much more sensitive to the stimulators and the drug trimebutine maleate. Trimebutine maleate was effective in reducing the colonic muscle hypercontractility of postinfectious irritable bowel syndrome mice. The findings may provide evidence for trimebutine maleate to treat postinfectious irritable bowel syndrome patients effectively. PMID:20371236

  10. HSP27 as a biomarker for predicting skin irritation in human skin and reconstructed organotypic skin model.

    PubMed

    Chen, Hongxia; Li, Shuhua; Meng, Tian; Zhang, Lei; Dai, Taoli; Xiang, Qi; Su, Zhijian; Zhang, Qihao; Huang, Yadong

    2014-04-21

    In vitro alternative tests aiming at replacing the traditional animal test for predicting the irritant potential of chemicals have been developed, but the assessing parameters or endpoints are still not sufficient. To discover novel endpoints for skin irritation responses, 2DE-based proteomics was used to analyze the protein expression in human skin exposed to sodium lauryl sulfate (SLS) following the test protocol of the European Centre for the Validation of Alternative Methods (ECVAM) in the present study. HSP27 was up-regulated most significantly among the eight identified proteins, consistent with our previous reports. Acid and basic chemicals were applied on human skin for further validation and results showed that the up-regulated expression of HSP27 was induced in 24h after the exposure. Skin-equivalent constructed with fibroblasts, basement membrane and keratinocytes was used to investigate the potential of HSP27 as a biomarker or additional endpoint for the hazard assessment of skin irritation. Our skin-equivalent (Reconstructed Organotypic Skin Model, ROSM) had excellent epidermal differentiation and was suitable for the skin irritation test. HSP27 also displayed an up-regulated expression in the ROSM in 24h after the irritants exposure for 15min. All these results suggest that HSP27 may represent a potential marker or additional endpoint for the hazard assessment of skin irritation caused by chemical products. PMID:24503015

  11. Prevalence and Determinants of Mucous Membrane Irritations in a Community Near a Cement Factory in Zambia: A Cross Sectional Study

    PubMed Central

    Nkhama, Emmy; Ndhlovu, Micky; Dvonch, J. Timothy; Siziya, Seter; Voyi, Kuku

    2015-01-01

    Exposure to cement dust has been associated with deleterious health effects in humans. This study investigated whether residing near a cement factory increases the risk of irritations to the mucous membranes of the eyes and respiratory system. A cross sectional study was conducted in Freedom Compound, a community bordering a cement factory in Chilanga, Zambia and a control community, Bauleni, located 18 km from the cement plant. A modified American Thoracic Society questionnaire was administered to 225 and 198 respondents aged 15–59 years from Freedom and Bauleni, respectively, to capture symptoms of the irritations. Respondents from Freedom Compound, were more likely to experience the irritations; adjusted ORs 2.50 (95% CI: 1.65, 3.79), 4.36 (95% CI (2.96, 6.55)) and 1.94 (95% CI (1.19, 3.18)) for eye, nose and sinus membrane irritations respectively. Cohort panel studies to determine associations of cement emissions to mucous membrane irritations and respiratory symptoms, coupled with field characterization of the exposure are needed to assess whether the excess prevalence of symptoms of mucous membrane irritations observed in Freedom compound are due to emissions from the cement factory. PMID:25602972

  12. Are Cosmetics Used in Developing Countries Safe? Use and Dermal Irritation of Body Care Products in Jimma Town, Southwestern Ethiopia

    PubMed Central

    Amasa, Wayessa; Santiago, Dante; Mekonen, Seblework; Ambelu, Argaw

    2012-01-01

    Background. Rabbit skin model was used to test skin irritation of the most commonly used cosmetic products in Jimma town, southwestern Ethiopia. The most commonly used cosmetics were Dove, Glysolid, College, Top Society, Fair and Lovely, Nivea, Lux, Magic fruit world, Solea, Body talk, Kris, Holly, Victoria, and Sweet Heart. Methods. Intact and abraded rabbit skins were tested for erythema and edema under shade and under sun exposure. Draize Primary Irritation Index (PII) was used to calculate skin irritation of each cosmetic. Cosmetic ingredients were analyzed from the labels. Results and Discussion. Only Dove cream caused no skin irritation except for an abraded skin under sun exposure for five consecutive days. It has been identified that application of cosmetics on abraded skin under sunny condition worsens the irritation. Cosmetic labels revealed that most ingredients used in all products were those restricted chemicals due to their adverse health effects. Conclusion. This study has concluded that use of cosmetics under sunshine and also on abraded skin increases skin irritation. Hence, those users who have abraded skin are advised not to apply those cosmetics on continuous basis specifically under sun exposure. PMID:23209460

  13. [On the Differential Diagnosis of Intractable Psychogenic Chronic Cough: Neuropathic Larynx Irritable - Gabapentin's Antitussive Action].

    PubMed

    Bonnet, U; Ossowski, A; Schubert, M; Gall, H; Steinkamp, I; Richter, L E; Khalil-Boutros, Y; Nefedev, A; Kuhlmann, R

    2015-10-01

    We present the case of a 76 year old female inpatient who suffered from a chronic intractable cough which arose simultaneously to a severe major depression and was secondary to an exorbitant psychological distress. Chronic cough had never been experienced before and was initially considered to have a mere psychogenic origin since a comprehensive and guideline-based diagnostic screening did not reveal any underlying somatic cause. However, several factors cast doubt on the solitary psychic genesis of the chronic cough: i) occurrence immediately after a penetrant cold, ii) embedding in other complaints of laryngeal hyperreagibility (larynx irritable), such as persistent globus pharyngeus sensation, throat clearing and episodic dysphonia, iii) first occurrence on old life, iv) erupting from sleep as well, v) persistence despite remission of the major depression, and v) no sustaining benefit from specific psychotherapy and speech therapy. Therefore, diagnostics were extended to apparative tools for objective evaluation of swallowing by using fiberoptic videoendoscopic (FEES) and videofluoroscopic (VFS) techniques, which revealed signs of laryngeal neuropathy but without evidence of penetration or aspiration. A co-existing small goiter and an impaired glucose tolerance along with a putative intracellular vitamin B12 or folate deficiency (as indirectly derived from an apparent hyperhomocysteinemia) were assumed to be responsible for the neuropathy and underwent specific treatments. The impaired glucose tolerance and putative vitamin deficit were compatible with a distal symmetric sensorimotoric, even subclinical polyneuropathy of the lower extremities. The larynx irritable improved under gabapentin being confirmed by drug removals several times, and finally calmed down almost completely under gabapentin, which was in line with the scant literature of this topic. Re-examination of the larynx per FEES nine months later showed no deficits any more under the well

  14. Treatment of Children With Attention-Deficit/Hyperactivity Disorder (ADHD) and Irritability: Results From the Multimodal Treatment Study of Children With ADHD (MTA)

    PubMed Central

    Fernández de la Cruz, Lorena; Simonoff, Emily; McGough, James J.; Halperin, Jeffrey M.; Arnold, L. Eugene; Stringaris, Argyris

    2015-01-01

    Objective Clinically impairing irritability affects 25% to 45% of children with attention-deficit/hyperactivity disorder (ADHD); yet, we know little about what interventions are effective in treating children with ADHD and co-occurring irritability. We used data from the Multimodal Treatment Study of Children With ADHD (MTA) to address 3 aims: to establish whether irritability in children with ADHD can be distinguished from other symptoms of oppositional defiant disorder (ODD); to examine whether ADHD treatment is effective in treating irritability; and to examine how irritability influences ADHD treatment outcomes. Method Secondary analyses of data from the MTA included multivariate analyses, and intent-to-treat random-effects regression models were used. Results Irritability was separable from other ODD symptoms. For treating irritability, systematic stimulant treatment was superior to behavioral management but not to routine community care; a combination of stimulants and behavioral treatment was superior to community care and to behavioral treatment alone, but not to medication alone. Irritability did not moderate the impact of treatment on parent- and teacher-reported ADHD symptoms in any of the 4 treatment groups. Conclusion Treatments targeting ADHD symptoms are helpful for improving irritability in children with ADHD. Moreover, irritability does not appear to influence the response to treatment of ADHD. Clinical trial registration information Multimodal Treatment Study of Children With Attention Deficit and Hyperactivity Disorder (MTA); http://www.clinicaltrials.gov; NCT00000388. PMID:25524791

  15. The spectrum of irritant-induced asthma: sudden and not-so-sudden onset and the role of allergy.

    PubMed

    Brooks, S M; Hammad, Y; Richards, I; Giovinco-Barbas, J; Jenkins, K

    1998-01-01

    A retrospective investigation of 86 asthmatic subjects defined clinical features of irritant-induced asthma and assessed the contributory role of an allergic predisposition. Three categories of asthma were evaluated: (1) occupational asthma due to a sensitizer (11 subjects, 13%); (2) irritant-induced asthma (54 persons, 63%); and (3) not occupational/environmental exposure-related asthma (21 subjects, 24%). Two distinct clinical presentations of irritant-induced asthma emerged: the first was sudden onset (29 subjects) and the second was not so sudden in onset (25 subjects). Sudden-onset, irritant-induced asthma was analogous to the reactive airways dysfunction syndrome. Clinical manifestations began immediately or within a few hours (always within 24 h) following an accidental, brief, and massive exposure. In contrast, for the not-so-sudden-onset asthma subjects, the causative irritant exposure was not brief, usually not massive, continued for > 24 h, and the initiation of asthma took longer to evolve. Eighty-eight percent of individuals with not-so-sudden irritant-induced asthma displayed an atopy/allergy status (p < 0.01). Some of the atopy/allergy subjects with presumed new-onset asthma were found to have suffered preexisting asthma that had been clinically quiescent for at least 1 year before the triggering exposure (16 persons). We conclude that preexisting allergic/atopy and/or preexisting asthma were significant contributors to the pathogenesis of not-so-sudden, irritant-induced asthma and emphasizes a critical interaction between environmental and host factors in the pathogenesis of asthma. PMID:9440566

  16. Identifying the Irritability Dimension of ODD: Application of a Modified Bifactor Model Across Five Large Community Samples of Children

    PubMed Central

    Burke, Jeffrey D.; Boylan, Khrista; Rowe, Richard; Duku, Eric; Stepp, Stephanie D.; Hipwell, Alison E.; Waldman, Irwin D.

    2014-01-01

    The importance of irritability as measured among the symptoms of oppositional defiant disorder (ODD) has dramatically come to the fore in recent years. New diagnostic categories rely on the distinct clinical utility of irritability, and models of psychopathology suggest it plays a key role in explaining developmental pathways within and between disorders into adulthood. However, only a few studies have tested multidimensional models of ODD, and the results have been conflicting. Further, consensus has not been reached regarding which symptoms best identify irritability. The present analyses use data from five large community data sets with five different measures of parent-reported ODD, comprising 16,280 youth in total, to help resolve these questions. Across the samples, ages ranged from 5 to 18, and included both boys and girls. Confirmatory factor analyses demonstrated that a modified bifactor model showed the best fit in each of the five data sets. The structure of the model included two correlated specific factors (irritability and oppositional behavior) in addition to a general ODD factor. In four of the five models, the best fit was obtained using the items of being touchy, angry and often losing temper as indicators of irritability. Given the structure of the models and the generally high correlation between the specific dimensions, the results suggest that irritability may not be sufficiently distinct from oppositional behavior to support an entirely independent diagnosis. Rather, irritability may be better understood as a dimension of psychopathology that can be distinguished within ODD, and which may be related to particular forms of psychopathology apart from ODD. PMID:25314267

  17. Measuring depth of injury (DOI) in an isolated rabbit eye irritation test (IRE) using biomarkers of cell death and viability.

    PubMed

    Jester, James V; Ling, Joseph; Harbell, John

    2010-03-01

    While DOI is a mechanistic correlate to the ocular irritation response, attempts to measure DOI in alternative tests have been limited to qualitative histopathologic assessment by veterinarian pathologists. The purpose of this study was to determine whether DOI could be measured objectively by fluorescent staining for biomarkers of cell death and viability using an ex vivo isolated rabbit eye (IRE) test. A panel of nine materials characterized by in vivo DOI were selected that caused slight (3% acetic acid and 5% SDS), mild (acetone, sodium hypochlorite and 10% acetic acid), moderate (cyclohexanol and parafluoroanaline) and severe (8% sodium hydroxide and 10% benzalkonium chloride) irritation. Materials were then tested using a modified IRE test with 3h recovery and then processed for cyrosectioning and staining using a TUNEL assay to detect cell death, phalloidin to detect intracellular f-actin and DAPI staining to detect nuclei. Control eyes treated with water showed intense phalloidin staining of the corneal epithelium and stromal keratocytes but no TUNEL labeling. In general, eyes treated with mild, moderate and severe irritants showed regions of TUNEL labeled epithelial and keratocyte nuclei with no phalloidin stain overlying phalloidin stained, undamaged cells. DOI measurements showed that slight irritants damaged<40% of the epithelium, mild and moderate irritants damaged>50% of the epithelium, extending at times into the anterior stroma (<20%), and the severe irritant damaged>50% of the stroma. Regression analysis between ex vivo and in vivo DOI showed a significant (p<0.007) correlation (r=0.785). These data suggest that fluorescent staining of fixed and sectioned tissue using biomarkers can be used to objectively identify the depth of injury caused by ocular irritants. PMID:19857567

  18. Relationship of asthma to irritant gas exposures in pulp and paper mills.

    PubMed

    Glindmeyer, H W; Lefante, J J; Freyder, L M; Friedman, M; Weill, H; Jones, R N

    2003-05-01

    The potential of chronic or acute irritant gas exposures to cause asthma or a variant condition, reactive airways dysfunction syndrome (RADS) was investigated by observing asthma incidence in a large working population, using person-years at risk (P-YR) to compute relative rates (RR). Health data came from employee examinations at 62 pulp and paper plants. The 39122 workers who denied asthma beginning before the observation period included: 19326 denying irritant exposures, with no gassing exposures; 19349 with self-reported irritant exposures, and no gassing; and 447 with documented gassings. Asthma was defined as self-reported asthma beginning after the start of observation. P-YR accrued from September 29, 1986, for the nonexposed and exposed workers, and from date of first gassing for gassed workers, and ended with disease onset in any who developed asthma. RR of asthma with 95% confidence intervals (CI95) were calculated for the exposed and gassed groups, relative to the nonexposed. Exposed (nongassed) workers had an elevated asthma rate, RR=1.48, CI95=1.17-1.86, after adjustment for effects of gender and number of examinations. The rate in gassed workers was not significantly elevated: RR=1.95, CI95=0.75-5.08. Of the five asthma cases occurring after gassings, none conformed to diagnostic criteria for RADS. Chronic exposures were associated with increased rate of asthma onset, which must be interpreted with caution because self-reported data defined both exposure category and disease. Documented gassings were not associated with significantly increased rate, and none of 447 gassed persons developed RADS. PMID:12735673

  19. Hydrophobically modified polymers can minimize skin irritation potential caused by surfactant-based cleansers

    PubMed Central

    Draelos, Zoe; Hornby, Sidney; Walters, Russel M; Appa, Yohini

    2013-01-01

    Summary Introduction The addition of hydrophobically modified polymers (HMPs) to cleansers that contain surfactants can create polymer–surfactant complexes that are less irritating to the skin than commercially available mild cleansers. Our objective was to compare the tolerability and efficacy of a test foaming liquid facial cleanser containing HMPs with a commercial liquid nonfoaming facial cleanser in women with sensitive skin. Methods In this randomized, prospective, double-blind, comparative study, women (n = 20 per group) with mild-to-moderate atopic dermatitis (AD), eczema, acne, or rosacea used a test gentle foaming liquid facial cleanser containing HMPs or a commercial gentle liquid nonfoaming facial cleanser daily for 3 weeks. Investigators assessed irritation and skin condition. Study subjects also assessed their skin properties and the performance of each cleanser. Results Clinicians as well as study subjects consistently rated the test cleanser as effective or slightly more effective at improving symptoms than the commercial cleanser, although no significant differences between groups were observed. At weeks 1 and 3, respectively, more users of the commercial cleanser reported irritation (20% and 10%) than users of the test cleanser (5% and 5%). In addition, subject self-assessments of skin condition and cleansing properties were slightly more improved with the test cleanser than with the commercial cleanser. Conclusions Both the test foaming cleanser containing HMPs and the commercial nonfoaming cleanser were effective and well accepted by most women in the study. Improvements were observed by both clinicians and subjects in the group using the test cleanser containing HMPs in all evaluated skin categories. PMID:24305430

  20. Evaluation of the irritancy and hypersensitivity potential following topical application of didecyldimethylammonium chloride

    PubMed Central

    Anderson, Stacey E.; Shane, Hillary; Long, Carrie; Lukomska, Ewa; Meade, B. Jean; Marshall, Nikki B.

    2016-01-01

    Didecyldimethylammonium chloride (DDAC) is a dialkyl-quaternary ammonium compound that is used in numerous products for its bactericidal, virucidal and fungicidal properties. There have been clinical reports of immediate and delayed hypersensitivity reactions in exposed individuals; however, the sensitization potential of DDAC has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of DDAC following dermal exposure in a murine model. DDAC induced significant irritancy (0.5 and 1%), evaluated by ear swelling in female Balb/c mice. Initial evaluation of the sensitization potential was conducted using the local lymph node assay (LLNA) at concentrations ranging from 0.0625–1%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.17%. Dermal exposure to DDAC did not induce increased production of IgE as evaluated by phenotypic analysis of draining lymph node B-cells (IgE+B220+) and measurement of total serum IgE levels. Additional phenotypic analyses revealed significant and dose-responsive increases in the absolute number of B-cells, CD4+ T-cells, CD8+ T-cells and dendritic cells in the draining lymph nodes, along with significant increases in the percentage of B-cells (0.25% and 1% DDAC) at Day 10 following 4 days of dermal exposure. There was also a significant and dose-responsive increase in the number of activated CD44 + CD4 + and CD8+ T-cells and CD86+ B-cells and dendritic cells following exposure to all concentrations of DDAC. These results demonstrate the potential for development of irritation and hypersensitivity responses to DDAC following dermal exposure and raise concerns about the use of this chemical and other quaternary ammonium compounds that may elicit similar effects. PMID:27216637

  1. FILAGGRIN DEFICIENCY CONFERS A PARACELLULAR BARRIER ABNORMALITY THAT REDUCES INFLAMMATORY THRESHOLDS TO IRRITANTS AND HAPTENS

    PubMed Central

    Scharschmidt, Tiffany C.; Man, Mao-Qiang; Hatano, Yutaka; Crumrine, Debra; Gunathilake, Roshan; Sundberg, John P.; Silva, Kathleen A.; Mauro, Theodora M.; Hupe, Melanie; Cho, Soyun; Wu, Yan; Celli, Anna; Schmuth, Matthias; Feingold, Kenneth R.; Elias, Peter M.

    2010-01-01

    Background Mutations in filaggrin (FLG) are associated with atopic dermatitis (AD), and are presumed to provoke a barrier abnormality. Yet, additional acquired stressors may be necessary, since the same mutations can result in a non-inflammatory disorder, ichthyosis vulgaris. Objective We examined here whether FLG deficiency alone suffices to produce a barrier abnormality; the basis for the putative abnormality; and its pro-inflammatory consequences. Methods Using the flaky-tail (ft/ft) mouse, which lacks processed flg due to a frame-shift mutation in profilaggrin that mimics some mutations in human AD, we assessed whether FLG deficiency provokes a barrier abnormality; further localized the defect; identified its subcellular basis; and assessed thresholds to irritant and hapten-induced dermatitis. Results Flaky-tail mice exhibit low-grade inflammation, with increased bidirectional, paracellular permeability of water-soluble xenobiotes due to impaired lamellar body secretion and altered stratum corneum extracellular membranes. This barrier abnormality correlates with reduced inflammatory thresholds to both topical irritants and haptens. Moreover, when exposed repeatedly to topical haptens, at doses that produce no inflammation in +/+ mice, ft/ft mice develop a severe AD-like dermatosis, with a further deterioration in barrier function and features of a th2 immunophenotype (increased CRTH + inflammation, elevated serum IgE levels, and reduced antimicrobial peptide [mBD3] expression). Conclusions FLG deficiency alone provokes a paracellular barrier abnormality in mice that reduces inflammatory thresholds to topical irritants/haptens, likely accounting for enhanced antigen penetration in FLG-associated AD. PMID:19733297

  2. Sleep and mood disorders in dry eye disease and allied irritating ocular diseases.

    PubMed

    Ayaki, Masahiko; Kawashima, Motoko; Negishi, Kazuno; Kishimoto, Taishiro; Mimura, Masaru; Tsubota, Kazuo

    2016-01-01

    The aim of the present study was to evaluate sleep and mood disorders in patients with irritating ocular diseases. The study design was a cross-sectional/case-control study conducted in six eye clinics. Out of 715 outpatients diagnosed with irritating ocular surface diseases and initially enrolled, 301 patients with dry eye disease (DED) and 202 age-matched control participants with other ocular surface diseases were analyzed. The mean Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS) scores were 6.4 ± 3.2 and 11.1 ± 5.7 for severe DED (n = 146), 5.5 ± 3.3 and 9.8 ± 4.0 for mild DED (n = 155), 5.5 ± 3.1 and 9.5 ± 6.6 for chronic conjunctivitis (n = 124), and 5.0 ± 3.3 and 8.9 ± 5.3 for allergic conjunctivitis (n = 78). There were significant differences among these diagnostic groups for PSQI (P < 0.05). Regression analysis of patients with DED revealed the PSQI and HADS scores were significantly correlated with the severity of DED (P < 0.05). Our results demonstrate that sleep quality in patients with DED is significantly worse than in patients with other irritating ocular surface diseases and it is correlated with the severity of DED. PMID:26927330

  3. Sleep and mood disorders in dry eye disease and allied irritating ocular diseases

    PubMed Central

    Ayaki, Masahiko; Kawashima, Motoko; Negishi, Kazuno; Kishimoto, Taishiro; Mimura, Masaru; Tsubota, Kazuo

    2016-01-01

    The aim of the present study was to evaluate sleep and mood disorders in patients with irritating ocular diseases. The study design was a cross-sectional/case-control study conducted in six eye clinics. Out of 715 outpatients diagnosed with irritating ocular surface diseases and initially enrolled, 301 patients with dry eye disease (DED) and 202 age-matched control participants with other ocular surface diseases were analyzed. The mean Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS) scores were 6.4 ± 3.2 and 11.1 ± 5.7 for severe DED (n = 146), 5.5 ± 3.3 and 9.8 ± 4.0 for mild DED (n = 155), 5.5 ± 3.1 and 9.5 ± 6.6 for chronic conjunctivitis (n = 124), and 5.0 ± 3.3 and 8.9 ± 5.3 for allergic conjunctivitis (n = 78). There were significant differences among these diagnostic groups for PSQI (P < 0.05). Regression analysis of patients with DED revealed the PSQI and HADS scores were significantly correlated with the severity of DED (P < 0.05). Our results demonstrate that sleep quality in patients with DED is significantly worse than in patients with other irritating ocular surface diseases and it is correlated with the severity of DED. PMID:26927330

  4. Clarithromycin-loaded liposomes offering high drug loading and less irritation.

    PubMed

    Liu, Xiaona; Sun, Wei; Zhang, Bo; Tian, Bin; Tang, Xing; Qi, Na; He, Haibing; Li, Huifang; Jin, Xiangqun

    2013-02-25

    The aim of this study was to develop an efficient method of preparing less irritant clarithromycin-loaded liposomes (CLA-Lip) for injection with a high drug loading and to evaluate their physicochemical characteristics before and after lyophilization. CLA-Lip were prepared using the film-dispersion method with sodium cholesterol sulfate (SCS) and n-hexyl acid as the regulators and then lyophilized. The liposomes were characterized in terms of their size, size distribution, zeta potential, morphology, in vitro release, haemolysis, and lyophilization and irritation testing was carried out. The TEM images revealed that the structure of the CLA-Lip were multilamellar and of a regular size of around 100 nm. In addition, the lyophilized CLA-Lip were characterized by DSC and Infrared spectroscopy to confirm the structure. H-bonding and salt-forming reactions were used to ensure that clarithromycin (CLA) was stably encapsulated in the liposomes. This method provided a 30-fold increase in the concentration of clarithromycin relative to that in aqueous solution. Sucrose was found to be the best protective agent and was added in an amount of 12.5% (w/v). According to the mouse scratch test and the rat paw lick test, the pain of CLA-Lip was significantly reduce by approximately 80% compared with the solution of clarithromycin phosphate. In addition, rabbit ear vein experiments produced similar results. These findings suggested that CLA-Lip was a stable delivery system with less irritation, which should be extremely suitable for clinical application. PMID:23337631

  5. Interactions of pathogens and irritant chemicals in land-applied sewage sludges (biosolids)

    PubMed Central

    Lewis, David L; Gattie, David K; Novak, Marc E; Sanchez, Susan; Pumphrey, Charles

    2002-01-01

    Background Fertilisation of land with processed sewage sludges, which often contain low levels of pathogens, endotoxins, and trace amounts of industrial and household chemicals, has become common practice in Western Europe, the US, and Canada. Local governments, however, are increasingly restricting or banning the practice in response to residents reporting adverse health effects. These self-reported illnesses have not been studied and methods for assessing exposures of residential communities to contaminants from processed sewage sludges need to be developed. Methods To describe and document adverse effects reported by residents, 48 individuals at ten sites in the US and Canada were questioned about their environmental exposures and symptoms. Information was obtained on five additional cases where an outbreak of staphylococcal infections occurred near a land application site in Robesonia, PA. Medical records were reviewed in cases involving hospitalisation or other medical treatment. Since most complaints were associated with airborne contaminants, an air dispersion model was used as a means for potentially ruling out exposure to sludge as the cause of adverse effects. Results Affected residents lived within approximately 1 km of land application sites and generally complained of irritation (e.g., skin rashes and burning of the eyes, throat, and lungs) after exposure to winds blowing from treated fields. A prevalence of Staphylococcus aureus infections of the skin and respiratory tract was found. Approximately 1 in 4 of 54 individuals were infected, including 2 mortalities (septicaemia, pneumonia). This result was consistent with the prevalence of S. aureus infections accompanying diaper rashes in which the organism, which is commonly found in the lower human colon, tends to invade irritated or inflamed tissue. Conclusions When assessing public health risks from applying sewage sludges in residential areas, potential interactions of chemical contaminants with low

  6. Less irritative action of wine and Japanese sake in rat stomachs: a comparative study with ethanol.

    PubMed

    Nakagiri, Akari; Fukushima, Kazuhiro; Kato, Shinichi; Takeuchi, Koji

    2006-02-01

    The ingestion of alcohol, especially in excess, causes acute gastric lesions and gastritis in humans, yet the mucosal irritative action of alcoholic beverages remains largely unknown. We examined the mucosal irritative action of whiskey, wine and Japanese sake in the rat stomach both ex vivo and in vitro, in comparison with ethanol. Under urethane anesthesia, a rat stomach was mounted in an ex vivo chamber, then superfused with saline, and the transmucosal potential difference (PD) was measured. After the basal PD had stabilized, the mucosa was exposed for 30 min to 2 ml of 15% ethanol, whiskey (containing 15% ethanol), white wine, or Japanese sake (the ethanol concentration of the latter two is 12-15%). In the in vitro study, rat epithelial cells (RGM1) were treated with the alcoholic beverages for 5 min, and the cell viability was determined with crystal violet. Ethanol or whiskey applied to the chamber caused a decrease in PD, while wine or Japanese sake did not. Histologically, surface epithelial damage was observed after exposure to both ethanol and whiskey, yet no damage was induced by white wine and Japanese sake. Likewise, both ethanol and whiskey markedly reduced the viability of RGM1 cells after 5 min of incubation, while neither white wine nor Japanese sake had any effect. In addition, supplementation of glucose significantly prevented the reduction in both PD and cell viability caused by ethanol. These results suggest that the mucosal irritative action of Japanese sake and white wine is much less pronounced than that of ethanol or whiskey and that the less damaging action of Japanese sake and white wine may be, at least partly, accounted for by the glucose contained in these alcoholic beverages. PMID:16534671

  7. [Frequency of celiac disease and irritable bowel syndrome coexistance and its influence on the disease course].

    PubMed

    Zwolińska-Wcisło, Małgorzata; Galicka-Latała, Danuta; Rozpondek, Piotr; Rudnicka-Sosin, Lucyna; Mach, Tomasz

    2009-01-01

    Celiac disease is increasingly recognized autoimmune enteropathy caused by a permanent gluten intolerance. Gluten is the main storage protein of wheat, in genetically predisposed individuals. Celiac disease risk in first degree relatives is about 10%. Diarrhea and changes of bowel movement, observed as well in celiac disease as in IBS, may lead to misdiagnosis of IBS basing on the Rome criteria or may be associated with coexistence of both diseases. The aim of the study was to assess the celiac disease prevalence in patients with irritable bowel syndrome. The study group comprised 200 patients (120 women and 80 men) aged 18-78 years (mean: 46.7 years) with diarrhoeal form of irritable bowel syndrome (IBS), according to the Rome criteria II. At the beginning and after a three month period anti tissue transglutaminase antibodies (IgA tTG) were estimated. Gastroscopy with biopsy where performed in those with IgA tTG titre above 1/200. 40 patients were immunologically positive and 14 of them have histopathologically proven celiac disease. In the group of patients with detected celiac disease, gluten free diet was applied besides the treatment with trimebutin or mebewerin, recommended for IBS. After 6 months the decrease of IgA tTG titre in the serum was observed. In 5 of these patients IgA tTG level was negative. It was associated with the significant decrease of clinical symptoms, such as diarrhea and flatulence. The remaining symptoms, such as abdominal pain, feeling of incomplete defecation demanded continuation of IBS treatment. With regard to often atypical celiac disease symptoms--adult active searching should be performed to differentiate from irritable bowel syndrome. PMID:19689036

  8. Clinical evaluation of Bilvadileha in the management of irritable bowel syndrome

    PubMed Central

    Tiwari, Ramanand; Pandya, Darshana H.; Baghel, Madhav Singh

    2013-01-01

    Irritable bowel syndrome (IBS) is one of the most common conditions encountered in clinical practice but one of the least well understood. Symptoms of this disorder are chronic, sometimes severe and often respond poorly to treatment, resulting in reduced quality of life. There is no specific test for IBS, although diagnostic tests may be performed to rule out other problems. In present clinical trial 51 patients of IBS were registered out of which 46 patients completed the treatment. Bilvadileha was administered for the duration of 12 weeks. The therapy showed statistically significant improvement in all the clinical features of IBS as well as in the IBS severity score. PMID:24696573

  9. Emerging Pharmacologic Therapies for Constipation-predominant Irritable Bowel Syndrome and Chronic Constipation.

    PubMed

    Eswaran, Shanti; Guentner, Amanda; Chey, William D

    2014-04-30

    Irritable bowel syndrome with constipation and chronic functional constipation are common digestive disorders that negatively impact quality of life and account for billions of dollars in health care costs. Related to the heterogeneity of pathogenesis that underlie these disorders and the failure of symptoms to reliably predict underlying pathophysiology, traditional therapies provide relief to only a subset of affected individuals. The evidence surrounding new and emerging pharmacologic treatments, which include both luminally and systemically acting drugs, is discussed here. These include agents such as lubiprostone, bile acid modulations, guanylate cyclase-C receptor agonists, serotonin receptor modulators and herbal therapies. PMID:24840367

  10. Loxapine Add-on for Adolescents and Adults with Autism Spectrum Disorders and Irritability

    PubMed Central

    Reed, Gregory; Cain, Sharon E.; Zhou, Xinghua; Barth, Francis X.; Aman, Michael G.; Palaguachi, Gladys I.; Mikhnev, Dmytro; Teng, Rujia; Andridge, Rebecca; Logan, Marilyn; Butler, Merlin G.; Han, Joan C.

    2015-01-01

    Abstract Objectives: Our clinical experience with low dose loxapine (5–15 mg/day) suggests promising efficacy and safety for irritability in autism spectrum disorders (ASD). We studied low dose loxapine prospectively in adolescents and adults with ASD and irritability. Additionally, we measured loxapine and metabolite concentrations, and brain-derived neurotrophic factor (BDNF) as a biomarker of neuromodulation. Methods: We performed a 12 week open trial of add-on loxapine in subjects, ages 13–65 years, diagnosed with ASD, and Aberrant Behavior Checklist-Irritability (ABC-I) subscale scores >14. Loxapine was dosed flexibly up to 15 mg daily, starting with 5 mg on alternate days. From weeks 1 to 6, other psychoactive medications were tapered if possible; from weeks 6 to 12, all medication doses were held stable. The primary outcome was the Clinical Global Impressions-Improvement subscale (CGI-I), ratings of Much Improved or Very Much Improved. Secondary outcomes were the ABC-I, Repetitive Behavior Scale-Revised, and Schalock Quality of Life scale. Serum BDNF and loxapine and metabolite concentrations were assayed. BDNF rs6265 was genotyped. Results: Sixteen subjects were enrolled; 12 completed all visits. Median age was 18 years (range 13–39). Median final loxapine dose was 7.5 mg/day (2.5–15). All 14 subjects (100%) with data at week 12 were rated as Much Improved on CGI-I at 12 weeks. Mean change on ABC-I at 12 weeks was −31%, p=0.01. Mean body mass index (BMI)-Z decreased between weeks 6 and 12, p=0.03. Side effects were minimal, and prolactin elevation occurred in only one subject. BDNF concentrations measured in 11 subjects increased significantly (p=0.04). Subjects with AG genotype for BDNF rs6265 required a lower dose of loxapine at study end, but had similar behavioral and BDNF concentration changes as the GG genotype. Conclusions: Low dose loxapine shows promise as a repurposed drug for irritability in ASD. Loxapine effects on BDNF warrant

  11. Prevention of sodium lauryl sulfate irritant contact dermatitis by Pro-Q aerosol foam skin protectant.

    PubMed

    Patterson, S E; Williams, J V; Marks, J G

    1999-05-01

    Eczematous skin disease is a serious work-related illness. Since 1995, reimbursement by insurance companies for treatment of skin diseases has become the largest cost source in some countries. This study was a randomized controlled trial (N = 20) of the efficacy of Pro-Q, a skin protectant product, in the prevention of contact dermatitis from sodium lauryl sulfate and urushiol, the resinous sap of poison ivy and poison oak. Pro-Q was significantly effective in reducing the irritation from sodium lauryl sulfate but did not prevent the allergic reaction to urushiol. PMID:10321615

  12. ["Theater of the body" -- the possibilities of psychodrama in the treatment of irritable bowel syndrome].

    PubMed

    Pénzes, István; Bánki, Adrienn; Túry, Ferenc

    2014-01-01

    We present the case and psychodrama therapy of a patient suffering from irritable bowel syndrome (IBS). First we provide a review of the literature on IBS. The therapeutic possibilities of psychodrama are in the dramatization of the perception of one's own body. Interpersonal communication is the focus of group work: the greatest challenge for the patient is the expression of her emotions, impulses, wishes - without somatization. The source of the non-specific psychotherapeutic effect is the free, spontaneous and creative communication and the rediscovery of play. PMID:25411224

  13. Hereditary angioedema presenting as irritable bowel syndrome: a case of early closure

    PubMed Central

    Benrajab, Karim M.; Singh, Gurkeerat; Obah, Eugene

    2015-01-01

    Abdominal pain is one of the most common reasons for outpatient and emergency department visits. We present one such case of early closure in a 32-year-old male with recurrent abdominal pain who was diagnosed with irritable bowel syndrome (IBS). Family history was suspicious for hereditary angioedema (HAE). The HAE workup came back positive, and the patient was started on prophylactic therapy, which led to an improvement in symptoms and quality of life. The purpose of this case is to create awareness among physicians to test for HAE in patients diagnosed with IBS who, based on their history or physical examination, have clinical suspicion for HAE. PMID:26486119

  14. Brain-gut interaction in irritable bowel syndrome: new findings of a multicomponent disease model.

    PubMed

    Schmulson, M J

    2001-02-01

    Knowledge on the pathophysiology of irritable bowel syndrome has evolved, beginning with disturbances in motility to visceral hypersensitivity, and ultimately to alterations in brain-gut bi-directional communication, where neurotransmitters such as serotonin play a key role. Recently, a multicomponent disease model that integrates all these alterations was proposed. This model is divided into physiological, cognitive, emotional and behavioral components that explain the gastrointestinal as well as the constitutional symptoms. In recent years there has been an explosion of research together with new developments in pharmacological treatments for IBS that support each component of this model. This review presents recent data in favor of these alterations in IBS. PMID:11347592

  15. A rare presentation of mucocele and irritation fibroma of the lower lip

    PubMed Central

    Rangeeth, B. N.; Moses, Joyson; Reddy, Veera Kishore Kumar

    2010-01-01

    The effects of chronic local irritation have been seen commonly in the form of fibroma or mucocele in children. We report a nine year old girl with the chief complaint of multiple swellings in the lower lip which was diagnosed both clinically and histologically as fibroma and mucocele. Surgical excision was done under local anesthesia with no post-operative complications. To our knowledge there was no other occurrence, either at the same site or at different locations, involving these two lesions in the oral mucosa. PMID:22114395

  16. Evaluation of electric arc furnace-processed steel slag for dermal corrosion, irritation, and sensitization from dermal contact.

    PubMed

    Suh, Mina; Troese, Matthew J; Hall, Debra A; Yasso, Blair; Yzenas, John J; Proctor, Debora M

    2014-12-01

    Electric arc furnace (EAF) steel slag is alkaline (pH of ~11-12) and contains metals, most notably chromium and nickel, and thus has potential to cause dermal irritation and sensitization at sufficient dose. Dermal contact with EAF slag occurs in many occupational and environmental settings because it is used widely in construction and other industrial sectors for various applications including asphaltic paving, road bases, construction fill, and as feed for cement kilns construction. However, no published study has characterized the potential for dermal effects associated with EAF slag. To assess dermal irritation, corrosion and sensitizing potential of EAF slag, in vitro and in vivo dermal toxicity assays were conducted based on the Organisation for Economic Co-operation and Development (OECD) guidelines. In vitro dermal corrosion and irritation testing (OECD 431 and 439) of EAF slag was conducted using the reconstructed human epidermal (RHE) tissue model. In vivo dermal toxicity and delayed contact sensitization testing (OECD 404 and 406) were conducted in rabbits and guinea pigs, respectively. EAF slag was not corrosive and not irritating in any tests. The results of the delayed contact dermal sensitization test indicate that EAF slag is not a dermal sensitizer. These findings are supported by the observation that metals in EAF slag occur as oxides of low solubility with leachates that are well below toxicity characteristic leaching procedure (TCLP) limits. Based on these results and in accordance to the OECD guidelines, EAF slag is not considered a dermal sensitizer, corrosive or irritant. PMID:24395402

  17. Computer-based bioassay for evaluation of sensory irritation of airborne chemicals and its limit of detection.

    PubMed

    Alarie, Y

    1998-04-01

    We expanded a previously described rule-based computerized method to recognize the sensory irritating effect of airborne chemicals. Using 2-chlorobenzylchloride (CBC) as a sensory irritant, characteristic modifications of the normal breathing pattern of exposed mice were evaluated by measuring the duration of braking (TB) after inspiration and the resulting decrease in breathing frequency. From the measurement of TB, each breath was then classified as normal (N) or sensory irritation (S). Using increasing exposure concentrations, the classification S increased from < or = 2% (equivalent to sham-exposure) to 100% within a narrow exposure concentration range. The potency of CBC was then evaluated by calculating the concentration necessary to produce 50% of the breaths classified as S, i.e., S50. This approach is easier to use than obtaining RD50 (decrease in respiratory frequency by 50%) when high exposure concentrations are difficult to achieve. Detection limits were also established for this bioassay and experiments were conducted to obtain a level of response just around these limits, in order to delineate the practicality of using this bioassay at low exposure concentrations. Using this approach, sensory irritation was the only effect induced by CBC at low exposure concentrations. However, bronchoconstriction and pulmonary irritation were superimposed on this effect at higher exposure concentrations. PMID:9630013

  18. Performance of porcine corneal opacity and permeability assay to predict eye irritation for water-soluble cosmetic ingredients.

    PubMed

    Van den Berghe, C; Guillet, M C; Compan, D

    2005-09-01

    The purpose of this paper is to report on the ability of an in-house porcine corneal opacity and permeability assay (PCOP) to predict eye irritation for cosmetic ingredients. Preliminary studies showed that the PCOP assay could accurately predict eye irritation class for liquid and water soluble materials. To broaden our experience a larger study on 50 cosmetic ingredients of this group was conducted. A prediction model (PM) was obtained based on only one endpoint-permeability measured after 30-min exposure O.D.30. This PM allows to distinguish nonirritating compounds (if O.D.30 < 0.35) from irritating (if O.D.30 > or = 0.35). Forty-nine of the 50 ingredients tested in the PCOP assay were accurately classified. The agreement was high (concordance 98%-kappa = 0.96). For 43 of the test substances an equation PM was obtained to predict the MAS. Despite satisfactory statistical coefficients this algorithm is not recommended due to wide 95% confidence intervals. These results confirm the usefulness of the PCOP for water-soluble cosmetic ingredients to discriminate nonirritants (MAS < or = 15) and irritants (MAS >15). For this type of ingredients the PCOP seems to be better than the BCOP to predict irritation class. Future work will be done to compare the BCOP and PCOP performances and to develop an appropriate protocol for water insoluble compounds. PMID:15922552

  19. Mood regulation in youth: research findings and clinical approaches to irritability and short-lived episodes of mania like symptoms

    PubMed Central

    Leigh, Eleanor; Smith, Patrick; Milavic, Gordana; Stringaris, Argyris

    2013-01-01

    Purpose of review Mood regulation problems, such as severe chronic irritability or short episodes of mania like symptoms are common, impairing and a topic of intense recent interest to clinicians, researchers and the DSM-5 process. Here we review the most recent findings about these two presentations and discuss approaches to their treatment. Recent findings Longitudinal and genetic findings suggest that chronic irritability should be regarded as a mood problem that is distinct from bipolar disorder. A proportion of children with short (less than 4 days) episodes of mania like symptoms seem to progress to classical (Type I or II) bipolar disorder over time in US clinic samples. In a UK sample, such episodes were independently associated with psychosocial impairment. The evidence base for the treatment of either irritability or short-lived episodes to mania-like symptoms is still small. Clinicians should be cautious with extrapolating treatments from classical bipolar disorder to these mood regulation problems. CBT-based approaches targeting general mood regulation processes may be effective for cases with severe irritability or short episodes of mania like symptoms. Summary There is increasing research evidence for the importance of mood regulation problems in the form of either irritability or short episodes of mania like symptoms in youth. The evidence base for their drug treatment has yet to be developed. CBT-based interventions to modify processes of mood regulation may be a useful and safe intervention for patients with these presentations. PMID:22569307

  20. Role of metabolic activation and the TRPA1 receptor in the sensory irritation response to styrene and naphthalene.

    PubMed

    Lanosa, Michael J; Willis, Daniel N; Jordt, Sven; Morris, John B

    2010-06-01

    The current study was aimed at examining the role of cytochrome P450 (CYP450) activation and the electrophile-sensitive transient receptor potential ankyrin 1 receptor (TRPA1) in mediating the sensory irritation response to styrene and naphthalene. Toward this end, the sensory irritation to these vapors was measured in female C57Bl/6J mice during 15-min exposure via plethysmographic measurement of the duration of braking at the onset of each expiration. The sensory irritation response to 75 ppm styrene and 7 ppm naphthalene was diminished threefold or more in animals pretreated with the CYP450 inhibitor metyrapone, providing evidence of the role of metabolic activation in the response to these vapors. The sensory irritation response to styrene (75 ppm) and naphthalene (7.6 ppm) was virtually absent in TRPA1-/- knockout mice, indicating the critical role of this receptor in mediating the response. Thus, these results support the hypothesis that styrene and naphthalene vapors initiate the sensory irritation response through TRPA1 detection of their CYP450 metabolites. PMID:20176620

  1. Human Cumulative Irritation Tests of Common Preservatives Used in Personal Care Products: A Retrospective Analysis of Over 45 000 Subjects.

    PubMed

    Walters, Russel M; Khanna, Preeya; Hamilton, Matthew; Mays, David A; Telofski, Lorena

    2015-11-01

    The cumulative irritation test (CIT) is an accepted method used to evaluate the skin irritation potential and safety of individual ingredients and formulas of leave-on skin care and cosmetic compounds. Here, we report the results of CITs collected by JOHNSON & JOHNSON Consumer Companies, Inc. (Skillman, NJ), part of an extensive tiered program to evaluate product safety. In the CIT, test formulations were applied to the skin of adults (18-70 years) with no known skin disease or allergies, 3 times per week for 2 weeks using semi-occlusive clinical patches. Preservatives were 1 of up to 16 components of test formulas, and included ethylenediaminetetraacetic acid, diazolidinyl urea, 1,3-Bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione, parabens, isothiazolinone, phenoxyethanol, sorbates, or benzoates. Skin sites were scored after each patch removal using a 5-point scale, with 0 = no visible reaction and 4 = erythema, marked edema, or substantial vesiculation. Scores were reported as percentage of maximal irritation score. Data were analyzed from 1363 CIT studies (over 45 000 subjects). There were no significant differences in percentage of maximal scores between formulas grouped by preservative types (p > .1). Median score across the entire dataset was 0.44, with most formulas showing none or mild irritation. Although seasonal variations were observed, no correlation was noted between score and preservative concentration. In conclusion, in a large, normal subject dataset, preservatives at typical in-use concentrations did not appear to contribute to skin irritation. PMID:26206148

  2. Slow-Growing Large Irritation Fibroma of the Anterior Hard Palate: A Case Report Using Immunohistochemical Analysis.

    PubMed

    Kinoshita, H; Ogasawara, T; Toya, T; Makihara, R; Hirai, R; Kawahara, E

    2016-07-01

    Irritation fibromas are recognized as fibrous lesions, usually reactive hyperplasias; however, the mechanism of enlargement is unclear. This paper reports on an abnormally large irritation fibroma of extremely gradual growth. The immunohistochemical features (CD34, α-SMA, vimentin, Ki-67, and TGF-α) of this irritation fibroma are presented to distinguish reactive hyperplasia from other true fibrous neoplasm diseases. In the only previous study, it was reported that the expression of TGF-α might be associated with the development of oral fibromas. Therefore, we investigated the relationship between this exceptionally-large fibrous lesion of extremely slow growth and the immunohistochemical reactivity of TGF-α, finding that, in contrast to the previous study, TGF-α was not expressed. This is the first study to evaluate the enlargement mechanism of such a large irritation fibroma using the approach of immunohistochemical analysis, and it indicates that such analysis can help elucidate the diverse causes and enlargement mechanisms of irritation fibromas. PMID:27408447

  3. A comparative study on irritation and residue aspects of five oxytetracycline formulations administered intramuscularly to calves, pigs and sheep.

    PubMed

    Nouws, J F; Smulders, A; Rappalini, M

    1990-07-01

    After intramuscular (IM) administration (dose 20 mg/kg) of three 20% (Terramycin/LA (product A), Alamycin LA (product B) and Terralon 20% LA (product C) and two 10% oxytetracycline (OTC) formulations (Engemycin 10% (product D) and Oxyject 10% (product E)), to calves, pigs and sheep, the OTC residue concentrations were determined in organs, muscle, fat, plasma, urine and at the injection sites at 10 days post injection (p.i.). At that time the irritation at the injection site was studied, too. The three 20%-formulations (products A, B, C) and one 10%-formulation (product E) induced considerable local irritation in and between the muscles. This was most pronounced in calves and pigs; in sheep the extent of irritation was limited. Ten days after administration of formulations A, B, C and E, OTC residues were found in organs and the OTC recovery at the injection sites varied widely among the three species. Following IM injection of product D minimal tissue irritation and no OTC residues could be detected at the injection site at 10 days p.i. The differences in local tissue irritation and the residue state of the carcass (including injection site) are related to the various solvent systems used in the formulations. PMID:2219655

  4. Evaluation of eye irritation by S-(-)-10,11-dihydroxyfarnesic acid methyl ester secreted by Beauveria bassiana CS1029.

    PubMed

    Son, Hyeong-U; Lee, Sang-Han

    2013-10-01

    The aim of this study was to investigate whether S-(-)-10,11-dihydroxyfarnesic acid methyl ester produced by cell subtype Beauveria bassiana CS1029 causes acute toxicity when used for cosmetic purposes by performing an eye irritation test. New Zealand white (NZW) rabbits were treated with a 100 mg/dose of S-(-)-10,11-dihydroxyfarnesic acid methyl ester according to standard procedure guidelines. No significant changes in terms of ocular lesions of the cornea, turbidity of the cornea, swelling of the eyelid or ocular discharge were observed in the methyl ester-treated groups, while sodium dioctyl sulfosuccinate, a positive control, caused severe toxicity. The anatomical and pathological observations indicate that the methyl ester produced by Beauveria bassiana CS1029 did not induce eye irritation in the lenses of the rabbits. The data suggest that the methyl ester evaluated in this study has promising potential as a cosmetic ingredient that does not irritate the eye. PMID:24137288

  5. Evaluation of eye irritation by S-(-)-10,11-dihydroxyfarnesic acid methyl ester secreted by Beauveria bassiana CS1029

    PubMed Central

    SON, HYEONG-U; LEE, SANG-HAN

    2013-01-01

    The aim of this study was to investigate whether S-(-)-10,11-dihydroxyfarnesic acid methyl ester produced by cell subtype Beauveria bassiana CS1029 causes acute toxicity when used for cosmetic purposes by performing an eye irritation test. New Zealand white (NZW) rabbits were treated with a 100 mg/dose of S-(-)-10,11-dihydroxyfarnesic acid methyl ester according to standard procedure guidelines. No significant changes in terms of ocular lesions of the cornea, turbidity of the cornea, swelling of the eyelid or ocular discharge were observed in the methyl ester-treated groups, while sodium dioctyl sulfosuccinate, a positive control, caused severe toxicity. The anatomical and pathological observations indicate that the methyl ester produced by Beauveria bassiana CS1029 did not induce eye irritation in the lenses of the rabbits. The data suggest that the methyl ester evaluated in this study has promising potential as a cosmetic ingredient that does not irritate the eye. PMID:24137288

  6. Elevated amygdala responses to emotional faces in youths with chronic irritability or bipolar disorder☆

    PubMed Central

    Thomas, Laura A.; Kim, Pilyoung; Bones, Brian L.; Hinton, Kendra E.; Milch, Hannah S.; Reynolds, Richard C.; Adleman, Nancy E.; Marsh, Abigail A.; Blair, R.J.R.; Pine, Daniel S.; Leibenluft, Ellen

    2013-01-01

    A major controversy in child psychiatry is whether bipolar disorder (BD) presents in children as severe, non-episodic irritability (operationalized here as severe mood dysregulation, SMD), rather than with manic episodes as in adults. Both classic, episodic BD and SMD are severe mood disorders characterized by deficits in processing emotional stimuli. Neuroimaging techniques can be used to test whether the pathophysiology mediating these deficits are similar across the two phenotypes. Amygdala dysfunction during face emotion processing is well-documented in BD, but little is known about amygdala dysfunction in chronically irritable youth. We compared neural activation in SMD (n = 19), BD (n = 19), and healthy volunteer (HV; n = 15) youths during an implicit face-emotion processing task with angry, fearful and neutral expressions. In the right amygdala, both SMD and BD exhibited greater activity across all expressions than HV. However, SMD and BD differed from each other and HV in posterior cingulate cortex, posterior insula, and inferior parietal lobe. In these regions, only SMD showed deactivation in response to fearful expressions, whereas only BD showed deactivation in response to angry expressions. Thus, during implicit face emotion processing, youth with BD and those with SMD exhibit similar amygdala dysfunction but different abnormalities in regions involved in information monitoring and integration. PMID:23977455

  7. Elevated amygdala responses to emotional faces in youths with chronic irritability or bipolar disorder.

    PubMed

    Thomas, Laura A; Kim, Pilyoung; Bones, Brian L; Hinton, Kendra E; Milch, Hannah S; Reynolds, Richard C; Adleman, Nancy E; Marsh, Abigail A; Blair, R J R; Pine, Daniel S; Leibenluft, Ellen

    2013-01-01

    A major controversy in child psychiatry is whether bipolar disorder (BD) presents in children as severe, non-episodic irritability (operationalized here as severe mood dysregulation, SMD), rather than with manic episodes as in adults. Both classic, episodic BD and SMD are severe mood disorders characterized by deficits in processing emotional stimuli. Neuroimaging techniques can be used to test whether the pathophysiology mediating these deficits are similar across the two phenotypes. Amygdala dysfunction during face emotion processing is well-documented in BD, but little is known about amygdala dysfunction in chronically irritable youth. We compared neural activation in SMD (n=19), BD (n=19), and healthy volunteer (HV; n=15) youths during an implicit face-emotion processing task with angry, fearful and neutral expressions. In the right amygdala, both SMD and BD exhibited greater activity across all expressions than HV. However, SMD and BD differed from each other and HV in posterior cingulate cortex, posterior insula, and inferior parietal lobe. In these regions, only SMD showed deactivation in response to fearful expressions, whereas only BD showed deactivation in response to angry expressions. Thus, during implicit face emotion processing, youth with BD and those with SMD exhibit similar amygdala dysfunction but different abnormalities in regions involved in information monitoring and integration. PMID:23977455

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

    PubMed Central

    Ratanasirintrawoot, Sutheera; Israsena, Nipan

    2016-01-01

    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. PMID:27184041

  9. Strategies for testing the irritation-signaling model for chronic lung effects of fine acid particles

    SciTech Connect

    Hattis, D.; Abdollahzadeh, S.; Franklin, C.A. )

    1990-03-01

    The irritation signaling model proposed that a long term contribution to chronic bronchitis might result from the repeated delivery of signals resulting from temporary localized acidification of the bronchial epithelium by the action of individual particles. This led to a prediction that the effectiveness of particles in inducing changes in mucus secreting cell numbers/types should depend on the number of particles deposited that contained a particular amount of acid--implying that particles below a certain size cutoff (and therefore lacking a minimum amount of acid) should be ineffective; and that particle potency per unit weight should be greatest at the cutoff and decline strongly above the cutoff. Since the development of this hypothesis both epidemiological observations and some experimental studies have tended to reinforce the notion that acid particles can make a contribution to relatively long lasting bronchitic-like changes, and enhance the desirability of more direct testing of the model. In this paper we develop a general theoretical framework for the contributions of environmental agents to chronic obstructive lung disease, and a series of alternative hypotheses against which the predictions of the irritant signaling model can be compared. Based on this, we suggest a research program that could be used to further develop and test the model and reasonable alternatives. 82 references.

  10. Aripiprazole for treating irritability in children & adolescents with autism: a systematic review

    PubMed Central

    Ghanizadeh, Ahmad; Tordjman, Sylvie; Jaafari, Nematollah

    2015-01-01

    Background & objectives: No clear therapeutic benefits of antipsychotics have been reported for the treatment of behavioural symptoms in autism. This systematic review provides an assessment of evidence for treating irritability in autism by aripiprazole. Methods: The databases of MEDLINE/PubMed and Google Scholar were searched for relevant articles about the effect of aripiprazole in children with autism. The articles were searched according to the inclusion and exclusion criteria specifed for this review. All the double-blind, controlled, randomized, clinical trials examining the efficacy of aripiprazole for treating children and adolescents with autism were included. Results: From the 93 titles identified, 26 were irrelevant and 58 were evaluated for more details. Only five articles met the inclusive criteria. The evidence from precise randomized double blind clinical trials of aripiprazole for the treatment of autism in children and adolescents was convincing enough to recommend aripiprazole. Adverse effects were not very common and were usually mild. Interpretation & conclusions: Current evidence suggests that aripiprazole is as effective and safe as risperidone for treating irritability in autism. However, further studies with larger sample size and longer duration are required. PMID:26458342

  11. Electroacupuncture versus Moxibustion for Irritable Bowel Syndrome: A Randomized, Parallel-Controlled Trial

    PubMed Central

    Shi, Yin; Chen, Yue-Hua; Yin, Xiao-Jun; Wang, An-Qi; Chen, Xing-Kui; Lu, Jin-Hua; Ji, Rong; Bao, Chun-Hui; Sun, Jie; Zhao, Ji-Meng; Wu, Huan-Gan

    2015-01-01

    Objective. To compare the impacts of electroacupuncture (EA) and mild moxibustion (Mox) on patients with irritable bowel syndrome (IBS). Method. Eighty-two IBS patients were randomly allocated into EA group (n = 41) and Mox group (n = 41) and received corresponding interventions for four weeks. Before and after the treatment, the Visual Analogue Scale for Irritable Bowel Syndrome (VAS-IBS) was used to evaluate the gastrointestinal symptoms and mental well-being; and the expression of serotonin (5-hydroxytryptamine, 5-HT), 5-HT3 receptor (5-HT3R), and 5-HT4 receptor (5-HT4R) in sigmoid mucosal tissue were detected. Results. Both EA and Mox can radically improve the total VAS-IBS score (P < 0.05), and EA was found to be more effective in ameliorating the symptom of constipation, while Mox was found to be more effective in ameliorating the symptom of diarrhoea. The abnormal expressions of 5-HT, 5-HT3R, and 5-HT4R in both groups were significantly improved after the treatments (all P < 0.05), and EA was superior to Mox in regulating the abnormally decreased 5-HT4R expression in IBS patients with constipation (P < 0.05). Conclusion. Electroacupuncture and mild moxibustion were both effective in improving IBS symptoms and modulate abnormal expressions of 5-HT, 5-HT3R, and 5-HT4R in the colonic tissue. PMID:26294923

  12. The influence of microemulsion structure on their skin irritation and phototoxicity potential.

    PubMed

    Rozman, Branka; Gosenca, Mirjam; Falson, Françoise; Gašperlin, Mirjana

    2016-02-29

    The purpose of this study was to examine skin irritation and phototoxicity potentials of several microemulsions (ME), all comprising approximately the same percentage of surfactant mixture, but varying oil/water content and consequently inner structure being either droplet-like (o/w ME, o/w ME carbomer, w/o ME and w/o ME white wax) or lamellar (gel-like ME). Two different in vitro methods were used: MTT assay (performed either on reconstructed human epidermis (RHE) or NCTC 2544 cells) and pig ear test. Neither assay revealed the difference among ME with droplet-like structure. Then again, pig ear test and MTT assay performed on RHE indicated that gel-like ME is more irritant compared to other tested ME, whereas no difference among formulations were observed by MTT assay on NCTC 2544 cells. The reasonable explanation is destruction and consequently uniform structure of ME upon dilution that is inevitable for testing on cell cultures. The results of phototoxicity test again indicated the increased potential of gel-like ME to cause adverse effects on skin. It can be concluded that for ME consisting of the same amount of identical surfactants but having different structure the latter represent a crucial factor that determines their dermal toxicity. PMID:26757147

  13. New aspects of the Slug Mucosal Irritation assay: predicting nasal stinging, itching and burning sensations.

    PubMed

    Lenoir, Joke; Adriaens, Els; Remon, Jean-Paul

    2011-10-01

    Stinging, itching and/or burning (SIB) sensations cannot be detected by animal tests or in vitro models. In the past, the Slug Mucosal Irritation (SMI) assay demonstrated a relation between an increased mucus production in slugs and an elevated incidence of SIB sensations in humans. A new 1-day SMI test procedure was developed focusing on the prediction of these short-term sensations. The objective of this study was to verify whether this new procedure is capable predicting mucosal tolerance of several marketed nasal formulations using the slug Arion lusitanicus. Irritation and tissue damage were quantified with a 5-day repeated exposure study by means of the mucus produced and proteins and enzymes released. The new protocol predicted SIB sensations by means of mucus production. The effects of six liquid nasal formulations were tested with both protocols, while five physiologic saline solutions were only tested with the new protocol to optimize it. None of the tested liquid nasal formulations resulted in tissue damage; however, exposure to the different formulations had a clear effect on the mucus production of the slugs and moderate discomfort was observed in some cases. These effects were due to the active ingredient, the presence of benzalkonium chloride as a preservative or the hyperosmolality of the formulation. For the most part results agreed with clinical data found in literature. It was concluded that the SMI assay, and the new 1-day protocol in particular, is a good tool to predict nasal clinical discomfort. PMID:21132841

  14. Long-term treatment of irritable bowel syndrome: results of a randomized controlled trial.

    PubMed

    Misra, S P; Thorat, V K; Sachdev, G K; Anand, B S

    1989-10-01

    To examine the long-term management of irritable bowel syndrome we conducted a two-part controlled therapeutic trial on 28 patients who had recovered completely after four to six weeks of treatment with ispaghula husk and propantheline. In part I patients were randomly divided into two groups. Group A received a placebo capsule while Group B continued with treatment as before. After six months the response to treatment was assessed according to a scoring system. The overall relapse rate in Group B was 46 per cent compared to 82 per cent in group A. With continued treatment patients in Group B became asymptomatic from the fourth month while patients in Group A continued to deteriorate. In part II, patients who had relapsed whilst on placebo received active treatment. Six of the seven who agreed to continue with the study became asymptomatic within four weeks. However, all the patients who were asymptomatic while on active treatment relapsed on discontinuation and again recovered on reinstitution of active treatment. We conclude that irritable bowel syndrome is a chronic relapsing disorder and that treatment with a combination of ispaghula husk and propantheline is effective, both in relieving symptoms and in the maintenance of remission. PMID:2697886

  15. Recommendations on chronic constipation (including constipation associated with irritable bowel syndrome) treatment

    PubMed Central

    Paré, Pierre; Bridges, Ronald; Champion, Malcolm C; Ganguli, Subhas C; Gray, James R; Irvine, E Jan; Plourde, Victor; Poitras, Pierre; Turnbull, Geoffrey K; Moayyedi, Paul; Flook, Nigel; Collins, Stephen M

    2007-01-01

    While chronic constipation (CC) has a high prevalence in primary care, there are no existing treatment recommendations to guide health care professionals. To address this, a consensus group of 10 gastroenterologists was formed to develop treatment recommendations. Although constipation may occur as a result of organic disease, the present paper addresses only the management of primary CC or constipation associated with irritable bowel syndrome. The final consensus group was assembled and the recommendations were created following the exact process outlined by the Canadian Association of Gastroenterology for the following areas: epidemiology, quality of life and threshold for treatment; definitions and diagnostic criteria; lifestyle changes; bulking agents and stool softeners; osmotic agents; prokinetics; stimulant laxatives; suppositories; enemas; other drugs; biofeedback and behavioural approaches; surgery; and probiotics. A treatment algorithm was developed by the group for CC and constipation associated with irritable bowel syndrome. Where possible, an evidence-based approach and expert opinions were used to develop the statements in areas with insufficient evidence. The nature of the underlying pathophysiology for constipation is often unclear, and it can be tricky for physicians to decide on an appropriate treatment strategy for the individual patient. The myriad of treatment options available to Canadian physicians can be confusing; thus, the main aim of the recommendations and treatment algorithm is to optimize the approach in clinical care based on available evidence. PMID:17464377

  16. The Gastrointestinal Irritation of Polygala Saponins and Its Potential Mechanism In Vitro and In Vivo

    PubMed Central

    Wen, Li; Xia, Nan; Tang, PeiPei; Hong, Yi; Wang, ZiZhen; Liu, YaJie; Liu, YanJu; Liu, JianJun; Li, XiangQiong

    2015-01-01

    Processing alters the pharmacological activity and reduces the gastrointestinal toxicity of the polygalae. To investigate the effect of processing, different glycosyl substituent products were tested. Hypnotic and subhypnotic doses of pentobarbital-induced sleep tests on mice were used to evaluate the sedative activity of polygala saponins with different glycosyl substituents; isolated gut motility experiment was employed to study excitatory effects of different polygala saponins; the gastrointestinal irritation effects of different polygala saponins were compared by measuring the levels of gastric PGE2 and intestinal TNF-α on mice. When compared with control, Onjisaponin B (OJB) and tenuifolin (TEN), but not senegenin (SNG), significantly increased the number of sleeping mice and prolonged the sleeping time (P < 0.05); 80, 40, and 20 mg/L of OJB and 80 mg/L of TEN, but not SNG, obviously changed the amplitude and frequency of isolated jejunum (P < 0.05); all the three compounds significantly decreased the level of gastric PGE2 but had no obvious influences on the reduction of intestinal TNF-α level. For sedative and hypnotic effects, OJB > TEN > SNG; for the protection form gastrointestinal irritation and damages, OJB > TEN > SNG. Therefore, in processing Polygala, glycosyl breaking may be related to the decline of pharmacological activity and gastrointestinal toxicity of polygala saponins. PMID:25705699

  17. Aerosolized GLP-1 for treatment of diabetes mellitus and irritable bowel syndrome.

    PubMed

    Siekmeier, Rüdiger; Hofmann, Thomas; Scheuch, Gerhard; Pokorski, Mieczyslaw

    2015-01-01

    Diabetes is a global burden and the prevalence of the disease, in particular diabetes mellitus type 2 is rapidly increasing worldwide. After introduction of insulin into clinical therapy about 90 years ago a major number of pharmaceuticals has been developed for treatment of diabetes mellitus type 2. One of these, the incretin glucagon-like peptide 1 (GLP-1), like insulin, needs subcutaneous administration causing inconvenience to patients. However, administration of GLP-1 plays also a role for treatment of irritable bowel syndrome (IBS). To improve patient convenience inhaled insulin (Exubera(®)) was developed and approved but failed market acceptance some years ago. Recently, another inhalative insulin (Afrezza(®)) received market approval and GLP-1 may serve as another candidate drug for inhalative administration. This review analyzes the current literature investigating alternative administration of GLP-1 and GLP-1 analogs focusing on inhalation. Several formulations for inhalative administration of GLP-1 and analogs were investigated in animal studies, whereas there are only few clinical data. However, feasibility of GLP-1 inhalation has been shown and should be further investigated as such type of drug administration may serve for improvement of therapy in patients with diabetes mellitus or irritable bowel syndrome. PMID:25427821

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

    PubMed

    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. PMID:27184041

  19. Irritable bowel syndrome and intestinal parasites: a view from South America.

    PubMed

    Vasquez-Rios, George; Machicado, Jorge D; Terashima, Angelica; Marcos, Luis A

    2016-01-01

    Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder of uncertain etiology. Several studies have proposed the possible role of intestinal parasites in the pathogenesis of IBS. We aimed to summarize the epidemiological studies that describe a possible link between intestinal parasites and IBS, with special interest in endemic areas for intestinal parasitism such as South America. A comprehensive review of the literature was conducted by using the keywords: irritable bowel syndrome, intestinal parasites, protozoan infection, soil-transmitted helminths and South America. Giardia lamblia may cause IBS symptoms that can persist several years after effective treatment. Dientamoeba fragilis can cause IBS-like symptoms, but low sensitive parasitological techniques may fail to detect it. Entamoeba histolytica can cause a chronic non-dysenteric colitis, but several studies have failed to find an association with IBS. The role of Blastocystis hominis in IBS remains controversial. In addition, epidemiological studies evaluating the effect of soil-transmitted helminths in IBS are scant. Symptoms elicited by intestinal parasites may resemble to those in IBS, especially in endemic areas such as South America, where both the prevalence of IBS and intestinal parasitism are high. Whether these organisms are the cause or contributing factors in IBS remains a subject of study. Routine parasitologicalexamination of stools in individuals who full-fit the criteria for IBS should be included upon initial assessment in endemic countries. PMID:27409092

  20. Inhibition of the colonic motor response to eating by pinaverium bromide in irritable bowel syndrome patients.

    PubMed

    Fioramonti, J; Frexinos, J; Staumont, G; Bueno, L

    1988-01-01

    The effect of pinaverium bromide on the colonic motor response to eating was investigated in 10 irritable bowel syndrome patients, by means of an intraluminal probe supporting 8 groups of electrodes. At each site examined from transverse to sigmoid colon, the electromyograms exhibited 2 kinds of spike bursts: short spike bursts (SSB) localized at one electrode, and long spike bursts (LSB), isolated, propagated orally or aborally over a few centimeters, or aborally propagated over the whole length of the colon investigated (migrating long spike bursts, MLSB). Recordings were continuously performed over 24 hr. Each patient received at 7.00 p.m. on day 1 and at noon on day 2 an 800-1000 Kcal meal preceded by IV administration of pinaverium bromide (4 mg) or placebo. After placebo administration, the duration of LSB activity and the number of MLSB were significantly increased over 3 postprandial hr by comparison with the 2 hr preceding the meal. After pinaverium injection no significant postprandial change in LSB and MLSB activity was noted. The SSB activity was not modified after the meals preceded by placebo or pinaverium injection. These results suggest that the inhibitory action of pinaverium bromide on postprandial colonic motility may support the clinical efficacy of this agent in the treatment of the irritable bowel syndrome. PMID:3371838

  1. Main ion channels and receptors associated with visceral hypersensitivity in irritable bowel syndrome

    PubMed Central

    de Carvalho Rocha, Heraldo Arcela; Dantas, Bruna Priscilla Vasconcelos; Rolim, Thaísa Leite; Costa, Bagnólia Araújo; de Medeiros, Arnaldo Correia

    2014-01-01

    Irritable bowel syndrome (IBS) is a very frequent functional gastrointestinal disorder characterized by recurrent abdominal pain or discomfort and alteration of bowel habits. The IBS physiopathology is extremely complex. Visceral hypersensitivity plays an important role in the pathogenesis of abdominal pain in both in vitro and in vivo models of this functional disorder. In order to obtain a general view of the participation of the main ion channels and receptors regarding the visceral hypersensitivity in the IBS and to describe their chemical structure, a literature review was carried out. A bibliographical research in the following electronic databases: Pubmed and Virtual Library in Health (BVS) was fulfilled by using the search terms “ion channels” “or” “receptors” “and” “visceral hypersensitivity” “or” “visceral nociception” “and” “irritable bowel syndrome”. Original and review articles were considered for data acquisition. The activation of the ATP ion-gated channels, voltage-gated sodium (Nav) and calcium (Cav) channels, as well as the activation of protease-activated receptors (PAR2), transient receptor potential vanilloide-1, serotonin, cannabinoids and cholecystokinin are involved in the genesis of visceral hypersensitivity in IBS. The involvement of ion channels and receptors concerning visceral hypersensitivity is noteworthy in IBS models. PMID:24976114

  2. In Vitro L6 Irritation Assay Predicts Clinical Injection Site Reactions for Small Molecules.

    PubMed

    Willy, Jeffrey A; Schulte, Nanette E; Kreklau, Emiko L; Walgren, Jennie L; Renninger, Matthew L; Baker, Thomas K

    2016-06-01

    Injection site reactions (ISRs) are commonly encountered in the development of parenteral drugs, and severe ISRs can lead to preclinical and clinical dose limiting toxicities. Tools to assess the risk of clinical ISRs during drug development are not well established. We developed an in vitro ISR screen using L6 rat myotubes to assess compounds for irritation risk. Reference compounds that were either known to induce ISRs or were non-irritating in the clinical setting were used to validate this method. We evaluated three compounds, two with known clinical ISRs (mitoxantrone and doxorubicin) and one without clinical ISR (metoprolol), using a preclinical in vivo rat model and the L6 in vitro model at clinically relevant concentrations, and showed that the L6 assay is a better prognostic indicator for clinical ISR risk. We then utilized this assay during early preclinical development to guide optimization of structure activity relationship (SAR), selection of dose concentrations for pre-clinical in vivo experiments, and prioritization of alternative formulations to minimize ISR risk. Our studies indicate that the L6 assay is a better measure of clinical ISR risk than current in vivo preclinical models, and that it can help guide not only compound selection, but also selection of dose concentration and formulation. PMID:26969369

  3. Application of SV40 T-transformed human corneal epithelial cells to evaluate potential irritant chemicals for in vitro alternative eye toxicity.

    PubMed

    Kim, Cho-Won; Park, Geon-Tae; Bae, Ok-Nam; Noh, Minsoo; Choi, Kyung-Chul

    2016-01-01

    Assessment of eye irritation potential is important to human safety, and it is necessary for various cosmetics and chemicals that may contact the human eye. Until recently, the Draize test was considered the standard method for estimating eye irritation, despite its disadvantages such as the need to sacrifice many rabbits for subjective scoring. Thus, we investigated the cytotoxicity and inflammatory response to standard eye irritants using SV40 T-transformed human corneal epithelial (SHCE) cells as a step toward development of an animal-free alternative eye irritation test. MTT and NRU assays of cell viability were performed to investigate the optimal experimental conditions for SHCE cell viability when cells were exposed to sodium dodecyl sulfate (SDS) as a standard eye irritant at 6.25×10(-3) to 1×10(-1)%. Additionally, cell viability of SHCE cells was examined in response to six potential eye irritants, benzalkonium chloride, dimethyl sulfoxide, isopropanol, SDS, Triton X-100 and Tween 20 at 5×10(-3) to 1×10(-1)%. Finally, we estimated the secretion level of cytokines in response to stimulation by eye irritants in SHCE cells. SHCE cells showed a good response to potential eye irritants when the cells were exposed to potential irritants for 10min at room temperature (RT), and cytokine production increased in a concentration-dependent manner, indicating that cytotoxicity and cytokine secretion from SHCE cells may be well correlated with the concentrations of irritants. Taken together, these results suggest that SHCE cells could be an excellent alternative in vitro model to replace in vivo animal models for eye irritation tests. PMID:27233534

  4. Larvicidal and irritant activities of hexane leaf extracts of Citrus sinensis against dengue vector Aedes aegypti L.

    PubMed Central

    Warikoo, Radhika; Ray, Ankita; Sandhu, Jasdeep Kaur; Samal, Roopa; Wahab, Naim; Kumar, Sarita

    2012-01-01

    Objective To assess the larvicidal and irritant activities of the hexane extracts of leaves of Citrus sinensis (C. sinensis) against the early fourth instars and female adults of Aedes aegypti (Ae. aegypti). Methods The larvicidal potential of the prepared leaf extract was evaluated against early fourth instar larvae of Ae. aegypti using WHO protocol. The mortality counts were made after 24 h and LC50 and LC90 values were calculated. The efficacy of extract as mosquito irritant was assessed by contact irritancy assays. Extract-impregnated paper was placed on a glass plate over which a perspex funnel with a hole on the top was kept inverted. Single female adult, 3-day old unfed/blood-fed, was released inside the funnel. After 3 min of acclimatization time, the time taken for the first take-off and total number of flights undertaken during 15 min were scored. Results The citrus leaf extracts from hexane possessed moderate larvicidal efficiency against dengue vector. The bioassays resulted in an LC50 and LC90 value of 446.84 and 1 370.96 ppm, respectively after 24 h of exposure. However, the extracts were proved to be remarkable irritant against adults Ae. aegypti, more pronounced effects being observed on blood-fed females than unfed females. The extract-impregnated paper was thus proved to be 7–11 times more irritable as compared with the control paper. Conclusions The hexane extracts from C. sinensis leaves are proved to be reasonably larvicidal but remarkably irritant against dengue vector. Further studies are needed to identify the possible role of extract as adulticide, oviposition deterrent and ovicidal agent. The isolation of active ingredient from the extract could help in formulating strategies for mosquito control. PMID:23569887

  5. MUTZ-3 derived Langerhans cells in human skin equivalents show differential migration and phenotypic plasticity after allergen or irritant exposure.

    PubMed

    Kosten, Ilona J; Spiekstra, Sander W; de Gruijl, Tanja D; Gibbs, Susan

    2015-08-15

    After allergen or irritant exposure, Langerhans cells (LC) undergo phenotypic changes and exit the epidermis. In this study we describe the unique ability of MUTZ-3 derived Langerhans cells (MUTZ-LC) to display similar phenotypic plasticity as their primary counterparts when incorporated into a physiologically relevant full-thickness skin equivalent model (SE-LC). We describe differences and similarities in the mechanisms regulating LC migration and plasticity upon allergen or irritant exposure. The skin equivalent consisted of a reconstructed epidermis containing primary differentiated keratinocytes and CD1a(+) MUTZ-LC on a primary fibroblast-populated dermis. Skin equivalents were exposed to a panel of allergens and irritants. Topical exposure to sub-toxic concentrations of allergens (nickel sulfate, resorcinol, cinnamaldehyde) and irritants (Triton X-100, SDS, Tween 80) resulted in LC migration out of the epidermis and into the dermis. Neutralizing antibody to CXCL12 blocked allergen-induced migration, whereas anti-CCL5 blocked irritant-induced migration. In contrast to allergen exposure, irritant exposure resulted in cells within the dermis becoming CD1a(-)/CD14(+)/CD68(+) which is characteristic of a phenotypic switch of MUTZ-LC to a macrophage-like cell in the dermis. This phenotypic switch was blocked with anti-IL-10. Mechanisms previously identified as being involved in LC activation and migration in native human skin could thus be reproduced in the in vitro constructed skin equivalent model containing functional LC. This model therefore provides a unique and relevant research tool to study human LC biology in situ under controlled in vitro conditions, and will provide a powerful tool for hazard identification, testing novel therapeutics and identifying new drug targets. PMID:26028481

  6. MUTZ-3 derived Langerhans cells in human skin equivalents show differential migration and phenotypic plasticity after allergen or irritant exposure

    SciTech Connect

    Kosten, Ilona J.; Spiekstra, Sander W.; Gruijl, Tanja D. de; Gibbs, Susan

    2015-08-15

    After allergen or irritant exposure, Langerhans cells (LC) undergo phenotypic changes and exit the epidermis. In this study we describe the unique ability of MUTZ-3 derived Langerhans cells (MUTZ-LC) to display similar phenotypic plasticity as their primary counterparts when incorporated into a physiologically relevant full-thickness skin equivalent model (SE-LC). We describe differences and similarities in the mechanisms regulating LC migration and plasticity upon allergen or irritant exposure. The skin equivalent consisted of a reconstructed epidermis containing primary differentiated keratinocytes and CD1a{sup +} MUTZ-LC on a primary fibroblast-populated dermis. Skin equivalents were exposed to a panel of allergens and irritants. Topical exposure to sub-toxic concentrations of allergens (nickel sulfate, resorcinol, cinnamaldehyde) and irritants (Triton X-100, SDS, Tween 80) resulted in LC migration out of the epidermis and into the dermis. Neutralizing antibody to CXCL12 blocked allergen-induced migration, whereas anti-CCL5 blocked irritant-induced migration. In contrast to allergen exposure, irritant exposure resulted in cells within the dermis becoming CD1a{sup −}/CD14{sup +}/CD68{sup +} which is characteristic of a phenotypic switch of MUTZ-LC to a macrophage-like cell in the dermis. This phenotypic switch was blocked with anti-IL-10. Mechanisms previously identified as being involved in LC activation and migration in native human skin could thus be reproduced in the in vitro constructed skin equivalent model containing functional LC. This model therefore provides a unique and relevant research tool to study human LC biology in situ under controlled in vitro conditions, and will provide a powerful tool for hazard identification, testing novel therapeutics and identifying new drug targets. - Highlights: • MUTZ-3 derived Langerhans cells integrated into skin equivalents are fully functional. • Anti-CXCL12 blocks allergen-induced MUTZ-LC migration.

  7. WILL THE MOUSE BIOASSAY FOR ESTIMATING SENSORY IRRITANCY OF AIRBORNE CHEMICALS (ASTM E 981-84) BE USEFUL FOR EVALUATION OF INDOOR AIR CONTAMINANTS

    EPA Science Inventory

    For many toxic inhalants, sensory irritation is the first detectable response. tandardized bioassay, ASTM E 981-84, that quantitates irritancy as a reduction in breathing rate of the mouse during inhalation exposure, has been developed. he validation of this screen for detecting ...

  8. Effectiveness of probiotics in irritable bowel syndrome: Updated systematic review with meta-analysis

    PubMed Central

    Didari, Tina; Mozaffari, Shilan; Nikfar, Shekoufeh; Abdollahi, Mohammad

    2015-01-01

    AIM: To investigate the efficacy of probiotics in irritable bowel syndrome (IBS) patients. METHODS: PubMed, Cochrane library, Scopus, Google Scholar, and Clinicaltrial.gov databases were searched for literature published between September 2007 and December 2013. The applied Mesh terms were “probiotics,” “irritable bowel syndrome,” and “irritable bowel syndrome treatment.” The collected data contained24 clinical trials, of which 15 were eligible for meta-analysis and nine were reviewed systematically. All studies were randomized placebo-controlled trials in patients with IBS that investigated the efficacy of probiotics in IBS improvement. The Jadad score was used to assess the methodological quality of trials. The quality scale ranges from 0 to 5 points, with a score ≤ 2 indicating a low quality report, and a score of ≥ 3 indicating a high quality report. Relative risk (RR), standardized effect size, and 95%CI were calculated using the DerSimonian-Laird method. The Cochran Q test was used to test heterogeneity with P < 0.05. Funnel plots were constructed and Egger’s and Begg-Mazumdar tests were performed to assess publication bias. RESULTS: A total of 1793 patients were included in the meta-analysis. The RR of responders to therapies based on abdominal pain score in IBS patients for two included trials comparing probiotics to placebo was 1.96 (95%CI: 1.14-3.36; P = 0.01). RR of responders to therapies based on a global symptom score in IBS patients for two included trials comparing probiotics with placebo was 2.43 (95%CI: 1.13-5.21; P = 0.02). For adequate improvement of general symptoms in IBS patients, the RR of seven included trials (six studies) comparing probiotics with placebo was 2.14 (95%CI: 1.08-4.26; P = 0.03). Distension, bloating, and flatulence were evaluated using an IBS severity scoring system in three trials (two studies) to compare the effect of probiotic therapy in IBS patients with placebo, the standardized effect size of mean

  9. Assessment of skin absorption and irritation potential of arachidonic acid and glyceryl arachidonate using in vitro diffusion cell techniques.

    PubMed

    Eppler, A R; Kraeling, M E K; Wickett, R R; Bronaugh, R L

    2007-11-01

    Arachidonic acid (AA), a precursor of pro-inflammatory mediators, and its glycerin ester, glyceryl arachidonate (GA), are reportedly used in cosmetic products. In vitro skin penetration of AA and GA and GA's ester hydrolysis was determined in flow-through diffusion cells. AA penetration with human and rat skin was 19.5% and 52.3% of the applied dose respectively, a substantial amount of which remained in the skin at 24h. Similar penetration results were obtained with GA in human skin. However, GA penetration through cultured skin (EpiDerm) was 51% of the applied dose, almost all of which appeared in the receptor fluid. At least 27.8% of GA penetrating skin was hydrolyzed to AA. In vitro methods were used to assess skin irritation in diffusion cells. Skin irritation of AA, sodium lauryl sulfate (SLS), and Tween 80 was determined by changes in transepidermal water loss (TEWL), skin viability (3-(4,5-dimethylthiaxol-2-yl)-2,5-diphenyltetrazolium bromide, MTT, formation), and cytokine release (IL-1alpha). SLS irritation was much less pronounced in an emulsion versus an aqueous vehicle. No significant irritation was observed in vitro from AA in an emulsion. This work predicts that AA would penetrate human skin in vivo and that it could be formed in skin from topically applied GA. PMID:17602815

  10. The Association of Irritability and Impulsivity with Suicidal Ideation Among 15- to 20-Year-Old Males

    ERIC Educational Resources Information Center

    Conner, Kenneth R.; Meldrum, Sean; Wieczorek, William F.; Duberstein, Paul R.; Welte, John W.

    2004-01-01

    Information on the association of impulsivity and measures of aggression with suicidal ideation in adolescents and young adults is limited. Data were gathered from a community sample of 625 adolescent and young adult males. Analyses were based on multivariate generalized estimating equations. Impulsivity and irritability were associated strongly…

  11. A placebo-controlled crossover study of iloperidone augmentation for residual anger and irritability in major depressive disorder

    PubMed Central

    Ionescu, Dawn F.; Fava, Maurizio; Kim, Daniel Ju Hyung; Baer, Lee; Shelton, Richard C.; Cusin, Cristina

    2016-01-01

    Background: Even when patients experience remission with antidepressants, many continue to report anger attacks and excessive irritability despite continued treatment. Iloperidone antagonizes 5-HT-2a, D2, and alpha-1 receptors, which can have anti-aggressive effects. We examined iloperidone’s safety and efficacy as an augmentation agent in outpatients with partially remitted major depressive disorder (MDD) with residual symptoms of anger and irritability. Methods: A total of 13 outpatients with partially remitted MDD [currently treated with selective serotonin reuptake inhibitors (SSRIs)] received four weeks of iloperidone or placebo, followed by one week of washout. Patients were then crossed over to the other treatment arm for 4 weeks. Treatment arms were randomized and double blind; and two sites were used for the study. Analyses compared treatment response using the Symptom Questionnaire (SQ) Anger/Hostility Subscale as the primary outcome measure. Results: There was no significant differential effect of iloperidone × weeks on the SQ Anger/Hostility Subscore over the course of the study, compared with placebo × weeks, regardless of administration order (p = 0.77). Conclusions: Iloperidone did not significantly outperform placebo on measures of anger or irritability in patients with partially remitted MDD and residual anger/irritability. PMID:26913173

  12. Endogenous inhibition of somatic pain is impaired in girls with irritable bowel syndrome compared with healthy girls

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endogenous pain inhibition is often deficient in adults with chronic pain conditions including irritable bowel syndrome (IBS). It is unclear whether deficiencies in pain inhibition are present in young children with IBS. The present study compared endogenous pain inhibition, somatic pain threshold, ...

  13. A Placebo-Controlled, Fixed-Dose Study of Aripiprazole in Children and Adolescents with Irritability Associated with Autistic Disorder

    ERIC Educational Resources Information Center

    Marcus, Ronald N.; Owen, Randall; Kamen, Lisa; Manos, George; McQuade, Robert D.; Carson, William H.; Aman, Michael G.

    2009-01-01

    Objective: To evaluate the short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Method: Two hundred eighteen children and adolescents (aged 6-17 years) with a diagnosis of autistic disorder, and with behaviors such as tantrums, aggression, self-injurious behavior, or a…

  14. Repellent, Irritant and Toxic Effects of 20 Plant Extracts on Adults of the Malaria Vector Anopheles gambiae Mosquito

    PubMed Central

    Deletre, Emilie; Martin, Thibaud; Campagne, Pascal; Bourguet, Denis; Cadin, Andy; Menut, Chantal; Bonafos, Romain; Chandre, Fabrice

    2013-01-01

    Pyrethroid insecticides induce an excito-repellent effect that reduces contact between humans and mosquitoes. Insecticide use is expected to lower the risk of pathogen transmission, particularly when impregnated on long-lasting treated bednets. When applied at low doses, pyrethroids have a toxic effect, however the development of pyrethroid resistance in several mosquito species may jeopardize these beneficial effects. The need to find additional compounds, either to kill disease-carrying mosquitoes or to prevent mosquito contact with humans, therefore arises. In laboratory conditions, the effects (i.e., repellent, irritant and toxic) of 20 plant extracts, mainly essential oils, were assessed on adults of Anopheles gambiae, a primary vector of malaria. Their effects were compared to those of DEET and permethrin, used as positive controls. Most plant extracts had irritant, repellent and/or toxic effects on An. gambiae adults. The most promising extracts, i.e. those combining the three types of effects, were from Cymbopogon winterianus, Cinnamomum zeylanicum and Thymus vulgaris. The irritant, repellent and toxic effects occurred apparently independently of each other, and the behavioural response of adult An. gambiae was significantly influenced by the concentration of the plant extracts. Mechanisms underlying repellency might, therefore, differ from those underlying irritancy and toxicity. The utility of the efficient plant extracts for vector control as an alternative to pyrethroids may thus be envisaged. PMID:24376515

  15. Gastrointestinal (GI) permeability is associated with trait anxiety in children with functional abdominal pain (FAP) and Irritable Bowel Syndrome (IBS)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    FAP and IBS affect 10-15% of school age children and bear many physiological similarities to irritable bowel syndrome (IBS) in adults (e.g., functional pain, visceral hyperalgesia). Animal models of IBS have suggested a relationship between neonatal stress and increased GI permeability later in life...

  16. Acrolein Causes TRPA1-Mediated Sensory Irritation and Indirect Potentiation of TRPV1-Mediated Pulmonary Chemoreflex Response

    EPA Science Inventory

    We previously demonstrated that acute exposure to acrolein causes immediate sensory irritation, with rapid decrease in heart rate (HR) and increase in inspiratory time (Ti), and potentiation of pulmonary chemoreflex response 24hrs later; of these effects only the latter is mediat...

  17. Zebrafish Locomotor Responses Demonstrate Irritant Effects of Fine Particulate Matter Sources and a Role for TRPA1

    EPA Science Inventory

    Fine particulate matter (PM) air pollution is a complex mixture of chemicals, the composition of which is determined by contributing sources, and has been linked to cardiopulmonary dysfunction. These effects stem in part from the irritating properties of PM constituents, which ...

  18. Repellent, irritant and toxic effects of 20 plant extracts on adults of the malaria vector Anopheles gambiae mosquito.

    PubMed

    Deletre, Emilie; Martin, Thibaud; Campagne, Pascal; Bourguet, Denis; Cadin, Andy; Menut, Chantal; Bonafos, Romain; Chandre, Fabrice

    2013-01-01

    Pyrethroid insecticides induce an excito-repellent effect that reduces contact between humans and mosquitoes. Insecticide use is expected to lower the risk of pathogen transmission, particularly when impregnated on long-lasting treated bednets. When applied at low doses, pyrethroids have a toxic effect, however the development of pyrethroid resistance in several mosquito species may jeopardize these beneficial effects. The need to find additional compounds, either to kill disease-carrying mosquitoes or to prevent mosquito contact with humans, therefore arises. In laboratory conditions, the effects (i.e., repellent, irritant and toxic) of 20 plant extracts, mainly essential oils, were assessed on adults of Anopheles gambiae, a primary vector of malaria. Their effects were compared to those of DEET and permethrin, used as positive controls. Most plant extracts had irritant, repellent and/or toxic effects on An. gambiae adults. The most promising extracts, i.e. those combining the three types of effects, were from Cymbopogon winterianus, Cinnamomum zeylanicum and Thymus vulgaris. The irritant, repellent and toxic effects occurred apparently independently of each other, and the behavioural response of adult An. gambiae was significantly influenced by the concentration of the plant extracts. Mechanisms underlying repellency might, therefore, differ from those underlying irritancy and toxicity. The utility of the efficient plant extracts for vector control as an alternative to pyrethroids may thus be envisaged. PMID:24376515

  19. Differentiation of skin sensitizers from irritant chemicals by interleukin-1α and macrophage inflammatory protein-2 in murine keratinocytes.

    PubMed

    Son, Dain; Na, Yirang; Cho, Wan-Seob; Lee, Byoung-Hee; Heo, Yong; Park, Jae-Hak; Seok, Seung Hyeok

    2013-01-10

    The development of novel alternative testing methods is required to identify the sensitizing capacity of chemicals as a replacement for animal experimentation. We aimed to evaluate in vitro assays as screening tools for detecting skin sensitizers. The murine epidermal keratinocyte cell line HEL-30 was exposed to 16 relevant skin sensitizers and 6 skin irritants. The dose causing 75% cell viability (CV(75)) measured by an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was chosen as a highest dose and three more doses (0.5×, 0.1×, and 0.01× of CV(75)) were tested. As parameters, levels of interleukin 1α (IL-1α), macrophage inflammatory protein 2 (MIP-2), IL-6, and IL-18 production were measured using 4 different doses. The accuracy of detecting sensitizers or irritants by IL-1α or MIP-2 alone was exactly same: 75% (12 out of 16) for sensitizers, 83% (5 out of 6) for irritants, and overall 77% (17 out of 22). However, combination of IL-1α and MIP-2 showed better accuracy: 94% (15 out of 16), 67% (4 out of 6), and overall 86% (19 out of 22). IL-6 and IL-18 could not differentiate sensitizers from irritants. This study suggests that the combination of pro-inflammatory cytokines IL-1α and MIP-2 in murine HEL-30 cells can be a reliable in vitro method for identifying chemicals that may act as skin sensitizers. PMID:23178550

  20. Functional Dyspepsia: Subtypes, Risk Factors, and Overlap with Irritable Bowel Syndrome in a Population of African Patients

    PubMed Central

    Nwokediuko, Sylvester Chuks; Ijoma, Uchenna; Obienu, Olive

    2012-01-01

    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. PMID:23213327

  1. The interpretation of Rome II criteria and method of assessment affect the irritable bowel syndrome classification of children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pediatric classification of irritable bowel syndrome (IBS) is complicated by the potential discrepancy, between parent and child report and by the interpretation of pain-stool relations in the Rome III classification system. The aim of this study was to compare IBS classification by diary and by chi...

  2. Food, fibre, bile acids and the pelvic floor: An integrated low risk low cost approach to managing irritable bowel syndrome

    PubMed Central

    Philpott, Hamish; Nandurkar, Sanjay; Lubel, John; Gibson, Peter R

    2015-01-01

    Patients presenting with abdominal pain and diarrhea are often labelled as suffering from irritable bowel syndrome, and medications may be used often without success. Advances in the understanding of the causes of the symptoms (including pelvic floor weakness and incontinence, bile salt malabsorption and food intolerance) mean that effective, safe and well tolerated treatments are now available. PMID:26525925

  3. Functional abdominal pain and irritable bowel syndrome in children and adolescents

    PubMed Central

    Chiou, Eric; Nurko, Samuel

    2011-01-01

    Functional abdominal pain (FAP) and irritable bowel syndrome (IBS) are both associated with recurrent abdominal pain and are among the most commonly diagnosed medical problems in pediatrics. The majority of patients with mild complaints improve with reassurance and time. For a distinct subset of patients with more severe and disabling illness, finding effective treatment for these disorders remains a challenge. Based on the biopsychosocial model of functional disease, the Rome III criteria have helped frame FAP and IBS in terms of being a positive diagnosis and not a diagnosis of exclusion. However, the lack of a single, proven intervention highlights the complex interplay of pathologic mechanisms likely involved in the development of childhood FAP and IBS and the need for a multidisciplinary, integrated approach. This article discusses the epidemiology, proposed mechanisms, clinical approach and therapeutic options for the management of FAP and IBS in children and adolescents. PMID:21731470

  4. Management of functional abdominal pain and irritable bowel syndrome in children and adolescents

    PubMed Central

    Chiou, Eric; Nurko, Samuel

    2010-01-01

    Functional abdominal pain (FAP) and irritable bowel syndrome (IBS) are among the most commonly diagnosed medical problems in pediatrics. Symptom-based Rome III criteria for FAP and IBS have been validated and help the clinician in making a positive diagnosis. The majority of patients with mild complaints improve with reassurance and time. For a distinct subset of patients with more severe and disabling illness, finding effective treatment for these disorders remains a challenge. Over the years, a wide range of therapies have been proposed and studied. The lack of a single, proven intervention highlights the complex interplay of biopsychosocial factors probably involved in the development of childhood FAP and IBS, and the need for a multidisciplinary, integrated approach. This article reviews the current literature on the efficacy of pharmacologic, dietary and psychosocial interventions for FAP and IBS in children and adolescents. PMID:20528117

  5. Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome.

    PubMed

    Ringel, Yehuda; Maharshak, Nitsan

    2013-10-15

    The pathophysiology of irritable bowel syndrome (IBS) is believed to involve alterations in the brain-gut axis; however, the etiological triggers and mechanisms by which these changes lead to symptoms of IBS remain poorly understood. Although IBS is often considered a condition without an identified "organic" etiology, emerging evidence suggests that alterations in the gastrointestinal microbiota and altered immune function may play a role in the pathogenesis of the disorder. These recent data suggest a plausible model in which changes in the intestinal microbiota and activation of the enteric immune system may impinge upon the brain-gut axis, causing the alterations in gastrointestinal function and the clinical symptoms observed in patients with IBS. This review summarizes the current evidence for altered intestinal microbiota and immune function in IBS. It discusses the potential etiological role of these factors, suggests an updated conceptual model for the pathogenesis of the disorder, and identifies areas for future research. PMID:23886861

  6. The inhibitory effect of some amphoteric surfactants on the irritation potential of alkylsulphates.

    PubMed

    Domínguez, J G; Balaguer, F; Parra, J L; Pelejero, C M

    1981-04-01

    Synopsis The physico-chemical and biological properties of an amphoteric/anionic system and its behaviour against a proteinic support have been thoroughly investigated. A considerable inhibition of adsorption of SLS (sodium lauryl sulphate) on human callus caused by the presence of definite amounts of AABet (alkyl-amido-betaines) in the treatment bath is observed. These physico-chemical results are in agreement with those obtained by some in vivo biological tests. A mechanism of the process via the formation of mixed micelles is postulated emphasizing the stability of such systems as a function of pH, the influence of the chain length of the amphoteric surfactant and the molar relative ratio SLS/AABet. Consequently, our work offers the possibility of a wide applicability of the synergic mixtures of both types of surfactants to inhibit considerably skin irritation of cosmetic finished products. PMID:19469927

  7. What does irritable bowel syndrome share with non-alcoholic fatty liver disease?

    PubMed Central

    Scalera, Antonella; Di Minno, Matteo Nicola Dario; Tarantino, Giovanni

    2013-01-01

    Non-alcoholic fatty liver disease (NAFLD) and irritable bowel syndrome (IBS) are two very common diseases in the general population. To date, there are no studies that highlight a direct link between NAFLD and IBS, but some recent reports have found an interesting correlation between obesity and IBS. A systematic PubMed database search was conducted highlighting that common mechanisms are involved in many of the local and systemic manifestations of NAFLD, leading to an increased cardiovascular risk, and IBS, leading to microbial dysbiosis, impaired intestinal barrier and altered intestinal motility. It is not known when considering local and systemic inflammation/immune system activation, which one has greater importance in NAFLD and IBS pathogenesis. Also, the nervous system is implicated. In fact, inflammation participates in the development of mood disorders, such as anxiety and depression, characteristics of obesity and consequently of NAFLD and, on the other hand, in intestinal hypersensitivity and dysmotility. PMID:24023483

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

    PubMed Central

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

    2014-01-01

    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. PMID:24976697

  9. [Chronic irritative urinary syndrome. Diagnostic value of cystoscopy, urinary cytology and biopsy].

    PubMed

    Guzmán Esquivel, J; Manzanilla, H; Zungri Telo, E; Da Silva, E A

    1997-01-01

    Chronic irritative urinary syndrome (CIUS), is a diagnostic concern for urologists from the moment that it becomes chronic and there is no etiologic diagnostic available. The objective of this study is to find out the diagnostic value of Cystoscopy, Urinary cytology and Biopsy of the vesical mucosa. A prospective, descriptive study was conducted in 30 patients who developed CIUS. Cystoscopy showed visible damage in 7 patients (31.8%); urinary cytology, 22 patients with cytologic changes (73.3%); and vesical biopsy, 24 patients with histologic changes (80.0%). The authors conclude that CIUS occurs more frequently in females than in males, the age range with higher incidence are 43 and 45 years. The most common diagnosis are unspecific chronic inflammatory changes followed by metaplasia. PMID:9494162

  10. The effect of enteric-coated, delayed-release peppermint oil on irritable bowel syndrome.

    PubMed

    Merat, Shahin; Khalili, Shadi; Mostajabi, Pardise; Ghorbani, Anahita; Ansari, Reza; Malekzadeh, Reza

    2010-05-01

    Herbal remedies, particularly peppermint, have been reported to be helpful in controlling symptoms of irritable bowel syndrome (IBS). We conducted a randomized double-blind placebo-controlled study on 90 outpatients with IBS. Subjects took one capsule of enteric-coated, delayed-release peppermint oil (Colpermin) or placebo three times daily for 8 weeks. We visited patients after the first, fourth, and eighth weeks and evaluated their symptoms and quality of life. The number of subjects free from abdominal pain or discomfort changed from 0 at week 0 to 14 at week 8 in the Colpermin group and from 0 to 6 in controls (P < 0.001). The severity of abdominal pain was also reduced significantly in the Colpermin group as compared to controls. Furthermore, Colpermin significantly improved the quality of life. There was no significant adverse reaction. Colpermin is effective and safe as a therapeutic agent in patients with IBS suffering from abdominal pain or discomfort. PMID:19507027

  11. Hot Topics in Primary Care: Individualizing Pharmacologic Management of Irritable Bowel Syndrome.

    PubMed

    Kuritzky, Louis

    2015-12-01

    Irritable bowel syndrome is a common gastrointestinal disorder with constipation, diarrhea, and mixed subtypes. The diagnosis is generally based on a detailed history utilizing the Rome III criteria. Alarm signals necessitate more extensive diagnostic evaluation. Nonpharmacologic options and over-the-counter remedies (e.g., loperamide) might not be supported by strong evidence, but are often chosen as initial treatment for their safety and tolerability. Psychological interventions may be beneficial. Newer pharmacologic agents such as alosetron, eluxadoline, linaclotide, lubiprostone, and rifaximin are supported by higher quality evidence than older agents such as antispasmodics and laxatives. Patients with IBS commonly report that clinicians offer insufficient empathy and validation of their symptoms. Physicians therefore should strive to improve communication methods that specifically provide such reassurance. Individualizing treatment based on patient values and preferences is essential. PMID:26845008

  12. ASSOCIATON BETWEEN INTIMATE PARTNER VIOLENCE AND IRRITABLE BOWEL SYNDROME: A POPULATION-BASED STUDY IN NICARAGUA

    PubMed Central

    Becker-Dreps, Sylvia; Morgan, Douglas; Peña, Rodolfo; Cortes, Loreto; Martin, Christopher F.; Valladares, Eliette

    2010-01-01

    Irritable bowel syndrome (IBS) is a disabling functional gastrointestinal disorder, which serves as a model for abdominal pain syndromes. An association between intimate partner violence and IBS has been shown among Caucasian women in the industrialized world. To determine whether this relationship transcends cultural boundaries, we conducted a population-based, cross-sectional survey in Nicaragua, using the innovative Health and Demographic Surveillance System in the León province. Women who had experienced physical intimate partner violence had significantly increased risk of IBS (OR 2.08, 95% CI, 1.35, 3.21), as did those who had experienced sexual intimate partner violence (OR 2.85, 95% CI 1.45, 5.59). These findings argue for intimate partner violence screening among Latina women with IBS. PMID:20558772

  13. Disability in Children and Adolescents With Irritable Bowel Syndrome and/or Fibromyalgia.

    PubMed

    Otu-Nyarko, Charles G; Gedalia, Abraham; Karpinski, Aryn C; Kolomensky, Andrew; Hyman, Paul E

    2015-11-01

    To compare disability and emotional health in individuals with irritable bowel syndrome (IBS), fibromyalgia, or both, patients completed the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III, childhood Functional Disability Inventory (FDI), and the Behavior Assessment System for Children, Second Edition. Patients' (age range 8-18 years, 19 IBS, 12 fibromyalgia, and 12 both) FDI scores showed greater disability than scores from historically healthy patients. Fibromyalgia (FDI 22.5 ± 12.7, P = 0.018) and patients with both (FDI 26.2 ± 13.8, P = 0.001) averaged greater disability than those with IBS (FDI 10.6 ± 7.9). Disability was correlated with anxiety and depression symptoms. Disability and psychological symptoms are important when evaluating individuals with fibromyalgia and IBS. PMID:26111293

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

    PubMed

    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 < .001). Sixty percent had a reduction of more than 50 points, indicative of clinical improvement. Initial severity score (p = .0004) and QRI conflict (p = .057) were directly correlated with a response to 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. PMID:23153384

  15. Renzapride: a new drug for the treatment of constipation in the irritable bowel syndrome.

    PubMed

    Scarpellini, Emidio; Tack, Jan

    2008-11-01

    Renzapride is a novel drug currently under clinical evaluation for the treatment of irritable bowel syndrome (IBS). Renzapride is a mixed 5-hydroxytryptamine type 4 (5-HT4) agonist and 5-HT3 receptor antagonist that has a stimulatory effect on gastrointestinal motility and transit, as established by in vivo and in vitro studies. Its therapeutic efficacy, tolerability and safety have been evaluated in diabetic gastroparesis in a single study, as well as in IBS in a few other studies. Phase II studies indicated potential beneficial effects on symptoms and bowel habits in patients with constipation-predominant IBS and mixed-type IBS. The outcome of Phase III studies is currently under evaluation. PMID:18922103

  16. Food: The Main Course to Wellness and Illness in Patients With Irritable Bowel Syndrome.

    PubMed

    Chey, William D

    2016-03-01

    Food sits at the intersection between gastrointestinal (GI) physiology and symptoms in patients with the irritable bowel syndrome (IBS). It is now clear that the majority of IBS sufferers associate eating a meal with their GI and non-GI symptoms. This is hardly surprising when one considers that food can affect a variety of physiologic factors (motility, visceral sensation, brain-gut interactions, microbiome, permeability, immune activation, and neuro-endocrine function) relevant to the pathogenesis of IBS. In recent years, clinical research has increasingly focused on diet as a treatment for IBS. There is a relative paucity of data from rigorous, randomized, controlled trials for any dietary intervention in IBS patients. Currently, the largest body of literature has addressed the efficacy of dietary restriction of fermentable oligo, di, monosaccharides, and polyols (FODMAPs). In the future, dietary treatments for IBS will move beyond the current focus on elimination to embrace supplementation with "functional" foods. PMID:26856749

  17. The Science, Evidence, and Practice of Dietary Interventions in Irritable Bowel Syndrome.

    PubMed

    Lacy, Brian E

    2015-11-01

    Irritable bowel syndrome (IBS) is a highly prevalent disorder that is characterized by symptoms of abdominal pain, bloating, constipation, and/or diarrhea. The diagnosis can be made using Rome III criteria or published guidelines after taking a thoughtful history, excluding warning signs, and performing a careful physical examination. Limited testing (ie, complete blood count and C-reactive protein level) may be useful in appropriate patients. A number of pharmacologic options are available, although many patients fail to respond to pharmacologic therapy. Although several IBS diets frequently are recommended, data supporting their use are limited. This article provides a rationale as to why specific diets might improve IBS symptoms and evaluates published trials. PMID:25769411

  18. Nutritional Interventions for Gastroesophageal Reflux, Irritable Bowel Syndrome, and Hypochlorhydria: A Case Report.

    PubMed

    Kines, Kasia; Krupczak, Tina

    2016-08-01

    Chronic gastrointestinal (GI) complaints are often treated with proton pump inhibitors (PPIs), antibiotics, and other medications that offer temporary relief of acute symptoms. Although these drugs are prescribed to provide promising results, new research indicates the drug treatments often mask unresolved physiological problems and cause further complications. Complex GI cases require a comprehensive assessment and a multifaceted approach. This case reports on the development of PPI-induced hypochlorhydria secondary to a PPI prescription for unresolved gastritis in a patient with irritable bowel syndrome. The patient's gastritis and hypochlorhydria symptoms resolved with the implementation of a comprehensive functional nutrition approach that incorporated dietary guidelines, lifestyle recommendations, and customized nutritional supplementation and herbs. PMID:27574495

  19. Transatlantic Irritability: Brunonian sociology, America and mass culture in the nineteenth century.

    PubMed

    Budge, Gavin

    2014-01-01

    The widespread influence exerted by the medical theories of Scottish doctor, John Brown, whose eponymously named Brunonianism radically simplified the ideas of his mentor, William Cullen, has not been generally recognised. However, the very simplicity of the Brunonian medical model played a key role in ensuring the dissemination of medical ideas about nervous irritability and the harmful effects of overstimulation in the literary culture of the nineteenth century and shaped early sociological thinking. This chapter suggests the centrality of these medical ideas, as mediated by Brunonianism, to the understanding of Romanticism in the nineteenth century, and argues that Brunonian ideas shaped nineteenth-century thinking about the effects of mass print culture in ways which continue to influence contemporary thinking about the effects of media. PMID:27132358

  20. [The low FODMAP diet as a therapy for irritable bowel syndrome].

    PubMed

    van der Waaij, Laurens A; Stevens, Janneke

    2014-01-01

    Irritable bowel syndrome (IBS) is a very common, sometimes disabling disorder for which there is a lack of effective treatments. Many patients report that the make-up of the diet has an effect on their symptoms. The western diet consists of many different molecules. Some of them are small, fermentable and cannot be absorbed (FODMAPs). The low FODMAP diet was recently developed in Australia. In randomised controlled trials 37-45% of IBS patients experience symptom reduction with this diet. The low FODMAP diet starts with a 6-week elimination phase. If symptoms decrease substantially, it is followed by a structured reintroduction phase of the various FODMAPs over several weeks, after which patients are left with a diet that is simpler to follow. PMID:24823855

  1. Editorial: new thoughts on the association between diverticulosis and irritable bowel syndrome.

    PubMed

    Spiller, Robin

    2014-12-01

    As our population ages it is increasingly common to encounter patients with irritable bowel syndrome (IBS)-like symptoms and diverticulosis, but the nature of the association is obscure. This Editorial discusses the paper from Japan showing an association between IBS-like symptoms and left-sided but not right-sided diverticulosis. The left colon with its higher motor activity is more likely to be associated with complications of diverticulosis, including perforation and abscess formation. The underlying pathophysiology of the syndrome of post-diverticulitis IBS is discussed and clinical markers of centrally driven symptoms suggested as a means to avoid ineffective colonic resections in those with IBS-like diverticular disease. PMID:25470583

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

    PubMed

    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. PMID:24976697

  3. Solitary nonspecific ileal ulcer. Diagnosis by coloileoscopy in a patient with previously assumed irritable bowel syndrome.

    PubMed

    Börsch, G; Jahnke, A; Bergbauer, M; Nebel, W

    1983-11-01

    We present a case of solitary nonspecific ileal ulcer found by coloileoscopy in a patient with previously assumed irritable bowel syndrome. Follow-up endoscopies two weeks after initiation of short-term prednisone therapy, and again four months later, demonstrated rapid and persistent healing. This observation raises the question of whether or not primary ileal ulcers are indeed as rare as previously assumed when only surgical and autopsy findings were taken into consideration. Also, the natural history of this clinical entity, in general, could be somewhat more benign than suggested by those ulcers in which complications make surgery necessary, since these cases may not adequately reflect the full clinical spectrum of nonspecific small-bowel ulcers. PMID:6628147

  4. Vulvodynia and Irritable Bowel Syndrome Treated With an Elimination Diet: A Case Report

    PubMed Central

    Drummond, Jessica; Ford, Deborah; Daniel, Stephanie; Meyerink, Tara

    2016-01-01

    Background A 28-y-old athletic woman was diagnosed with vulvodynia and long-term irritable bowel syndrome (IBS) and was treated successfully with an elimination diet. Case/Intervention In the course of 6 mo of nutrition therapy utilizing an elimination diet, specific foods triggering abdominal bloating and pain, and vulvovaginal pain were identified. In the course of treatment, the nutrition and supplement program instituted for this patient allowed her to return to her prior functional level without pain (including sexual activity) and resolution of her IBS. She has remained symptom free for at least 6 mo posttreatment. Conclusion This case demonstrates the potential usefulness of incorporating a customized nutritional approach to determine proinflammatory foods in patients with chronic vulvodynia and overlapping IBS. Long-term pain resolution and healthy sexual functioning in this case was supported by food elimination and nutritional supplementation. PMID:27574494

  5. Airway hyperresponsiveness, prevalence of chronic respiratory symptoms, and lung function in workers exposed to irritants.

    PubMed

    Kremer, A M; Pal, T M; Boleij, J S; Schouten, J P; Rijcken, B

    1994-01-01

    The association between occupational exposure to airway irritants and the prevalence of chronic respiratory symptoms and level of lung function, and whether these associations were modified by airway hyperresponsiveness, smoking, and a history of allergy were studied in 668 workers from synthetic fibre plants. Respiratory symptoms were recorded with a self administered Dutch version of the British Medical Research Council questionnaire, with additional questions on allergy. Airway responsiveness was measured by a 30 second tidal breathing histamine challenge test. On the basis of job titles and working department, the current state of exposure of all workers was characterised as (1) no exposure, reference group; (2) white collar workers; (3) SO2 HCl, SO4(2); (4) polyester vapour; (5) oil mist and vapour; (6) polyamide and polyester vapour; (7) multiple exposure. Workers exposed to airway irritants were not simultaneously exposed to airborne dust. Airway hyperresponsiveness (AHR), defined as a 20% fall in forced expiratory volume in one second (FEV1) at < or = 32 mg/ml histamine, was present in 23% of the subjects. The association between exposure groups and prevalence of symptoms was estimated by means of multiple logistic regression; the association with level of lung function (forced vital capacity (FVC), FEV1, maximum mid-expiratory flow rate (MMEF)) was estimated by means of multiple linear regression. Both methods allow simultaneous adjustment for potential confounding factors. The exposure groups were associated with a higher prevalence of chronic respiratory symptoms. Lower prevalence of symptoms was found for workers exposed to SO2, HCl, and SO4(2-), most likely due to pre-employment selection procedures. Current smoking, AHR, and a history of allergy were significantly associated with a higher prevalence of chronic respiratory symptoms, independent of each other, and independent of irritant exposure. The association between exposure and prevalence of

  6. Assessment of phototoxicity, skin irritation, and sensitization potential of polystyrene and TiO2 nanoparticles

    NASA Astrophysics Data System (ADS)

    Park, Yoon-Hee; Jeong, Sang Hoon; Yi, Sang Min; Hyeok Choi, Byeong; Kim, Yu-Ri; Kim, In-Kyoung; Kim, Meyoung-Kon; Son, Sang Wook

    2011-07-01

    The human skin equivalent model (HSEM) is well known as an attractive alternative model for evaluation of dermal toxicity. However, only limited data are available on the usefulness of an HSEM for nanotoxicity testing. This study was designed to investigate cutaneous toxicity of polystyrene and TiO2 nanoparticles using cultured keratinocytes, an HSEM, and an animal model. In addition, we also evaluated the skin sensitization potential of nanoparticles using a local lymph node assay with incorporation of BrdU. Findings from the present study indicate that polystyrene and TiO2 nanoparticles do not induce phototoxicity, acute cutaneous irritation, or skin sensitization. Results from evaluation of the HSEMs correspond well with those from animal models. Our findings suggest that the HSEM might be a useful alternative model for evaluation of dermal nanotoxicity.

  7. Airway irritation and cough evoked by acid: from human to ion channel

    PubMed Central

    Gu, Qihai; Lee, Lu-Yuan

    2011-01-01

    Inhalation or aspiration of acid solution evokes airway defense responses such as cough and reflex bronchoconstriction, resulting from activation of vagal bronchopulmonary C-fibers and Aδ afferents. The stimulatory effect of hydrogen ion on these sensory nerves is generated by activation of two major types of ion channels expressed in these neurons: a rapidly activating and inactivating current mediated through ASICs, and a slow sustaining current via activation of TRPV1. Recent studies have shown that these acid-evoked responses are elevated during airway inflammatory reaction, revealing the potential convergence of a wide array of inflammatory signaling on these ion channels. Since pH in the airway fluid drops substantially in patients with inflammatory airway diseases, these heightened stimulatory effects of acid on airway sensory nerves may play a part in the manifestation of airway irritation and excessive cough under those pathophysiological conditions. PMID:21543258

  8. Rifaximin for the treatment of diarrhea-predominant irritable bowel syndrome.

    PubMed

    Kane, John S; Ford, Alexander C

    2016-04-01

    Irritable bowel syndrome (IBS) is a chronic, functional bowel disorder characterized by abdominal pain or discomfort and altered bowel habit. The pathophysiology is unclear, but may include altered gut motility, visceral hypersensitivity, abnormal central pain processing, chronic low-grade intestinal inflammation, or disturbances in the gut microbiome. These etiological mechanisms, alongside environmental factors such as stress and anxiety, vary between individuals and represent potential targets for treatment. Rifaximin is a poorly absorbed oral antibiotic proposed to act on the gut microenvironment, used in the treatment of travelers' diarrhea and hepatic encephalopathy. Clinical trials suggest the drug can reduce global IBS symptoms and improve bloating, abdominal pain, and stool consistency in some patients with non-constipated IBS, leading to Food and Drug Administration approval in the United States. This article considers the pharmacology of rifaximin, the evidence for its use in IBS, and the safety and tolerability of the drug. PMID:26753693

  9. False-positive, follicular and irritant patch test reactions to metal salts.

    PubMed

    Fischer, T; Rystedt, I

    1985-02-01

    853 hard metal workers were patch tested with nickel sulphate 5%, potassium dichromate 0.5% and cobalt chloride 1%, each in petrolatum. Non-allergic reactions appeared in 6.5% of the nickel tests, 13% of the chromium tests and 18.3% of the cobalt tests. Most of the individuals with positive, poral or pustular reactions were retested with serial dilutions of metal salts in pet. and in water. The accuracy of a positive initial nickel reaction was 83%, a chromium reaction 40% and a cobalt reaction 62%. The nonallergic reactions were partly reproducible and correlated with both the type of patch test material and with individual factors. Weak and moderately strong positive patch test reactions to metal salts may be irritant and should be checked with serial dilution tests or at least be retested. A reduction of the cobalt chloride concentration from 1% to 0.5% in the standard test material is discussed. PMID:3157537

  10. Lower irritation microemulsion-based rotigotine gel: formulation optimization and in vitro and in vivo studies

    PubMed Central

    Wang, Zheng; Mu, Hong-Jie; Zhang, Xue-Mei; Ma, Peng-Kai; Lian, Sheng-Nan; Zhang, Feng-Pu; Chu, Sheng-Ying; Zhang, Wen-Wen; Wang, Ai-Ping; Wang, Wen-Yan; Sun, Kao-Xiang

    2015-01-01

    Background Rotigotine is a potent and selective D1, D2, and D3 dopaminergic receptor agonist. Due to an extensive first-pass effect, it has a very low oral bioavailability (approximately 0.5% in rats). Purpose The present investigation aimed to develop a microemulsion-based hydrogel for transdermal rotigotine delivery with lower application site reactions. Methods Pseudoternary phase diagrams were constructed to determine the region of oil in water (o/w)-type microemulsion. Central composite design was used to support the pseudoternary phase diagrams and to select homogeneous and stable microemulsions with an optimal amount of rotigotine permeation within 24 hours. In vitro skin permeation experiments were performed, using Franz diffusion cells, to compare rotigotine-loaded microemulsions with rotigotine solutions in oil. The optimized formulation was used to prepare a microemulsion-based hydrogel, which was subjected to bioavailability and skin irritancy studies. Results The selected formulations of rotigotine-loaded microemulsions had enhanced flux and permeation coefficients compared with rotigotine in oil. The optimum microemulsion contained 68% water, 6.8% Labrafil®, 13.44% Cremophor® RH40, 6.72% Labrasol®, and 5.04% Transcutol® HP; the drug-loading rate was 2%. To form a microemulsion gel, 1% Carbomer 1342 was added to the microemulsion. The bioavailability of the rotigotine-loaded microemulsion gel was 105.76%±20.52% with respect to the marketed rotigotine patch (Neupro®). The microemulsion gel irritated the skin less than Neupro. Conclusion A rotigotine microemulsion-based hydrogel was successfully developed, and an optimal formulation for drug delivery was identified. This product could improve patient compliance and have broad marketability. PMID:25609965

  11. Clinical Practice Guideline: Irritable bowel syndrome with constipation and functional constipation in the adult.

    PubMed

    Mearin, Fermín; Ciriza, Constanza; Mínguez, Miguel; Rey, Enrique; Mascort, Juan José; Peña, Enrique; Cañones, Pedro; Júdez, Javier

    2016-06-01

    In this Clinical Practice Guideline we discuss the diagnostic and therapeutic approach of adult patients with constipation and abdominal complaints at the confluence of the irritable bowel syndrome spectrum and functional constipation. Both conditions are included among the functional bowel disorders, and have a significant personal, healthcare, and social impact, affecting the quality of life of the patients who suffer from them. The first one is the irritable bowel syndrome subtype, where constipation represents the predominant complaint, in association with recurrent abdominal pain, bloating, and abdominal distension. Constipation is characterized by difficulties with or low frequency of bowel movements, often accompanied by straining during defecation or a feeling of incomplete evacuation. Most cases have no underlying medical cause, and are therefore considered as a functional bowel disorder. There are many clinical and pathophysiological similarities between both disorders, and both respond similarly to commonly used drugs, their primary difference being the presence or absence of pain, albeit not in an "all or nothing" manner. Severity depends not only upon bowel symptom intensity but also upon other biopsychosocial factors (association of gastrointestinal and extraintestinal symptoms, grade of involvement, and perception and behavior variants). Functional bowel disorders are diagnosed using the Rome criteria. This Clinical Practice Guideline has been made consistent with the Rome IV criteria, which were published late in May 2016, and discuss alarm criteria, diagnostic tests, and referral criteria between Primary Care and gastroenterology settings. Furthermore, all the available treatment options (exercise, fluid ingestion, diet with soluble fiber-rich foods, fiber supplementation, other dietary components, osmotic or stimulating laxatives, probiotics, antibiotics, spasmolytics, peppermint essence, prucalopride, linaclotide, lubiprostone, biofeedback

  12. Gender-related differences in irritable bowel syndrome: Potential mechanisms of sex hormones

    PubMed Central

    Meleine, Mathieu; Matricon, Julien

    2014-01-01

    According to epidemiological studies, twice as many women as men are affected by irritable bowel syndrome (IBS) in western countries, suggesting a role for sex hormones in IBS pathophysiology. Despite growing evidence about the implications of sex hormones in IBS symptom modulation, data on mechanisms by which they influence disease development are sparse. This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS. The scientific bibliography was searched using the following keywords: irritable bowel syndrome, sex, gender, ovarian hormone, estradiol, progesterone, testosterone, symptoms, pain, sensitivity, motility, permeability, stress, immune system, brain activity, spinal, supraspinal, imaging. Ovarian hormones variations along the menstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations. They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception. These hormones can also modulate the susceptibility to stress, which is a pivotal factor in IBS occurrence and symptom severity. For instance, estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function. In conclusion, whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS, they arguably modulate IBS onset and symptomatology. However, our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender. Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS. Finally, investigation of brain-gut interactions is critical

  13. Comparative acute toxicity and primary irritancy of the ethylidene and vinyl isomers of norbornene.

    PubMed

    Ballantyne, B; Myers, R C; Klonne, D R

    1997-01-01

    The acute toxicity and primary irritancy of the industrial chemicals 5-ethylidene-2-norbornene (ENB) and 5-vinyl-2-norbornene (VNB) were studied. They are of moderate acute peroral toxicity in the rat, with LD50 values for ENB of 2.54 (male) and 5.66 (female) ml kg(-1), and for VNB of 5.90 (male) and 11.9 (female) ml kg(-1). Percutaneous toxicity is slight in the rabbit by 24-h occluded contact, with no mortalities for ENB up to 8.0 ml kg(-1) and only one mortality (male) at 16.0 ml kg(-1) VNB. Dynamically generated saturated vapor atmosphere LT50 values for ENB in the rat were 75 (male) and 125 (female) min, and for VNB they were 28 (male) and 37 (female) min. The 4-h LC50 values for ENB were 2717 (male) and 3015 (female) ppm, and for VNB they were 2231 (male) and 2518 (female) ppm. Intravenously, the ENB LD50 ranged from 0.09 (male rabbit) to 0.11 ml kg(-1) (female); corresponding LD50 values for VNB were 0.10-0.05 mg kg(-1). Acute neurotoxic signs were seen by the intravenous and inhalation routes of exposure, including tremors, ataxia and convulsions; the latter were sufficient to cause vertebral column luxation or fracture, producing spinal cord compression and resultant hindlimb paralysis. Both ENB and VNB are moderately irritating to the skin (rabbit), causing erythema and edema, but not necrosis. Both materials cause slight conjunctival hyperemia and chemosis in rabbits, but not corneal injury. PMID:9285533

  14. Transdermal delivery of naloxone: skin permeation, pharmacokinetic, irritancy and stability studies.

    PubMed

    Panchagnula, Ramesh; Bokalial, Ranadeep; Sharma, Puneet; Khandavilli, Sateesh

    2005-04-11

    The current investigation aims to evaluate ex vivo, in vivo performance, stability and irritancy potential of a transdermal formulation of naloxone (NLX) developed at our laboratory at different concentrations (10, 20 and 30mg/g of gel) in a transdermal reservoir patch. Ex vivo permeation studies were performed by employing porcine and rat skins. In vivo performance was assessed in Sprague-Dawley rats by single and multiple application of the patch. Further stability of the formulation was established for 3 months at accelerated stability conditions as per ICH guidelines. Amongst the barriers used the rat skin was found to be more permeable than the porcine epidermis and the flux across each barrier increased with increasing thermodynamic activity of drug in the gel. Based on ex vivo data, the surface area (SA) of the patch was predicted to be 39.6 cm(2) in order to achieve therapeutic blood levels. Upon single dose administration, the steady-state levels were maintained from 4-48 h, which proves the clear advantage of transdermal delivery system over the current mode of administration, i.e., intravenous (i.v.) bolus which is effective upto a maximum of 1.5h. Upon multiple dose administration, the sustained steady state for 12h, even after patch removal proves the formation of drug depot in the skin. The formulations were found to be stable with respect to NLX assay and penetration enhancer efficacy upto 3 months under accelerated stability conditions. The alteration of penetration barrier function, as evidenced by increased trans epidermal water loss (TEWL) was not accompanied by any significant amount of skin irritation measured using laser doppler velocimetry (LDV). The developed transdermal delivery system of NLX is efficacious, stable and safe upon single and multiple dose applications each lasting for 48 h. PMID:15778059

  15. Topical application of silymarin reduces chemical-induced irritant contact dermatitis in BALB/c mice.

    PubMed

    Han, Mi Hwa; Yoon, Won Kee; Lee, Hyunju; Han, Sang-Bae; Lee, Kiho; Park, Song-Kyu; Yang, Kyu-Hwan; Kim, Hwan Mook; Kang, Jong Soon

    2007-12-15

    Irritant contact dermatitis (ICD) is a non-allergic local inflammatory reaction of a skin and one of the most frequent occupational health problems. Silymarin has been clinically used in Europe for a long time to treat liver diseases and also known to have anti-cancer and anti-inflammatory activities. In the present study, we report that topical application of silymarin reduces chemical-induced ICD. Topical application of 2,4-dinitrochlorobenzene (DNCB) induced an ear swelling in BALB/c mice and silymarin suppressed DNCB-induced increase in ear thickness. Prophylactic and therapeutic application of silymarin showed similar effect on DNCB-induced increase in ear thickness and skin water content. In addition, phobor ester- or croton oil-induced increase in ear thickness was also inhibited by silymarin treatment. Silymarin also blocked neutrophil accumulation into the ear induced by these irritants. Further study demonstrated that DNCB-induced tumor necrosis factor-alpha (TNF-alpha) expression in mouse ear was suppressed by silymarin. DNCB-induced expression of KC, one of the main attractors of neutrophil in mice, and adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) and E-selectin in mouse ear were also inhibited by silymarin. Moreover, TNF-alpha-induced expression of cytokines, such as TNF-alpha and IL-1beta, and a chemokine, IL-8, were suppressed by silymarin treatment in human keratinocyte cell line, HaCaT. Silymarin also blocked TNF-alpha- and DNCB-induced NF-kappaB activation in HaCaT. Collectively, these results demonstrate that topically applied silymarin inhibits chemical-induced ICD in mice and this might be mediated, at least in part, by blocking NF-kappaB activation and consequently inhibiting the expression of cytokines and adhesion molecules. PMID:17996674

  16. Nondermal irritating hyperosmotic nanoemulsions reduce treatment times in a contamination model of wound healing.

    PubMed

    Connell, Sean; Li, Jianming; Durkes, Abigail; Zaroura, Mohammed; Shi, Riyi

    2016-07-01

    Increased microbial burden within the wound often complicates wound healing and may lead to subsequent infection or delayed healing. Here, we investigate a novel topical for addressing wound contamination that utilizes hyperosmotic saccharides with a cell membrane disrupting emulsion. These hyperosmotic nanoemulsions (HNE) were administered topically in a full-thickness biopsy model of wound healing. Results show that HNE were well tolerated in noninfected animals with no indications of dermal irritation or acute toxicity. Additionally, HNE was able to reduce bacterial bioburden (Escherichia coli and Enterococcus faecalis) levels by 3 logs within 24 h when wounds were inoculated with 5 × 10(6) total CFU. These bactericidal values were similar to wounds treated with silver sulfadiazine. Wound closure showed HNE wounds closed in 7.6 ± 0.2 days while SSD and control required 10.2 ± 0.4 and 10.4 ± 0.3 days, respectively. HNE maintained a moist wound environment, were well debrided, and exhibited improved hemostatic response. Further histological examination revealed enhanced granulation tissue as compared to silver sulfadiazine and control cohorts. These results were corroborated with 3D topographical imprints of the wounds at day 14 which qualitatively showed a smoother surface. In contrast, silver sulfadiazine appeared to delay wound closure. Finally, dermal sensitization and irritation studies conducted in guinea pig and rabbits did not reveal any acute dermal side effects from HNE exposure. The cumulative data indicates nonantibiotic-based HNEs may be a promising topical treatment for the management of contaminated wounds. PMID:27090977

  17. Airway irritation, inflammation, and toxicity in mice following inhalation of metal oxide nanoparticles.

    PubMed

    Larsen, Søren T; Jackson, Petra; Poulsen, Steen S; Levin, Marcus; Jensen, Keld A; Wallin, Håkan; Nielsen, Gunnar D; Koponen, Ismo K

    2016-11-01

    Metal oxide nanoparticles are used in a broad range of industrial processes and workers may be exposed to aerosols of the particles both during production and handling. Despite the widespread use of these particles, relatively few studies have been performed to investigate the toxicological effects in the airways following inhalation. In the present study, the acute (24 h) and persistent (13 weeks) effects in the airways after a single exposure to metal oxide nanoparticles were studied using a murine inhalation model. Mice were exposed 60 min to aerosols of either ZnO, TiO2, Al2O3 or CeO2 and the deposited doses in the upper and lower respiratory tracts were calculated. Endpoints were acute airway irritation, pulmonary inflammation based on analyses of bronchoalveolar lavage (BAL) cell composition, DNA damage assessed by the comet assay and pulmonary toxicity assessed by protein level in BAL fluid and histology. All studied particles reduced the tidal volume in a concentration-dependent manner accompanied with an increase in the respiratory rate. In addition, ZnO and TiO2 induced nasal irritation. BAL cell analyses revealed both neutrophilic and lymphocytic inflammation 24-h post-exposure to all particles except TiO2. The ranking of potency regarding induction of acute lung inflammation was Al2O3 = TiO2 < CeO2 ≪ ZnO. Exposure to CeO2 gave rise to a more persistent inflammation; both neutrophilic and lymphocytic inflammation was seen 13 weeks after exposure. As the only particles, ZnO caused a significant toxic effect in the airways while TiO2 gave rise to DNA-strand break as shown by the comet assay. PMID:27323801

  18. [Effectiveness of pinaverium bromide therapy on colonic motility disorders in irritable bowel syndrome].

    PubMed

    Wittmann, T; Fehér, A; Rosztóczy, A; Jánosi, J

    1999-02-28

    The special patterns of the slow wave activity in irrittable bowel syndrome by means of surface electromyography were examined and the effect of pinaverium bromide on the symptoms and on the colonic motility in this disease was estimated. Twenty two patients with irritable bowel syndrome and 7 healthy controls were selected to the study. The clinical symptoms were abdominal pain and bloating in all patients, constipation in 9, and diarrhoea in 6 cases. Surface electromyography was carried out before and on the 14th day of the treatment with pinaverium bromide (50 mg t. i. d). The colonic motility was analysed in a 2 hour fasting and a 2 hour postprandial period following a standard (800 kCal) meal. The slow wave frequency of 0.01-0.04 Hz were selected and analysed. The mean frequency of activity peaks (n/10 min) and power-index (area under curve, microV 10 min) were measured. For statistical analysis Student's t-test was applied. Electromyogram of patients with irritable bowel syndrome showed a significant increase of the measured colonic motility parameters both in fasting and postprandial states. Fourteen days of pinaverium bromide treatment was able to significantly reduce the intensity of the colonic motor activity. Administration of pinaverium bromide completely released in 6 and significantly improved the abdominal pain in other 12 patients, while the bloating disappeared in 12 and was significantly improved in 5 from 22 patients. Pinaverium bromide was able to normalise the stool frequency: the weekly number of stools was decreased from 16 to 7 in the patients complaining diarrhoea ant it was increased from 2 to 6 in the patients with constipation. PMID:10204402

  19. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in irritable bowel syndrome

    PubMed Central

    Chang, L.; Sundaresh, S.; Elliott, J.; Anton, P. A.; Baldi, P.; Licudine, A.; Mayer, M.; Vuong, T.; Hirano, M.; Naliboff, B. D.; Ameen, V. Z.; Mayer, E. A.

    2009-01-01

    Enhanced stress responsiveness has been implicated as a potential mechanism contributing to the pathophysiology of irritable bowel syndrome (IBS), and should be reflected in altered function of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. Both of these systems can modulate mucosal immune function. The aims of this study were: (i) to characterize the basal circadian rhythm of adrenocorticotropin hormone (ACTH) and cortisol in IBS vs healthy controls; (ii) to compare stimulated ACTH, cortisol and noradrenaline responses to a pelvic visceral stressor (sigmoidoscopy) in IBS and controls; and (iii) to correlate neuroendocrine responses with colonic mucosal cytokine expression and symptoms in IBS. Two separate studies were conducted in women. In Study 1, basal cortisol levels were analysed in 41 IBS and 25 controls using 24-h collections of plasma ACTH and cortisol (q10 min sampling). In Study 2, 10 IBS patients with diarrhoea (IBS-D) and 10 controls underwent sigmoidoscopy with measurements of stimulated neuroendocrine responses and cytokine mRNA expression in colonic tissue. Basal ACTH levels were significantly blunted (P < 0.05), while basal and stimulated plasma cortisol levels were higher in patients. Basal cortisol levels prior to an experimental visceral stressor positively correlated with anxiety symptoms (P < 0.004), but not IBS symptoms. Irritable bowel syndrome patients with diarrhoea had significantly decreased mRNA expression of mucosal cytokines [interleukin (IL)-2, IL-6] in the sigmoid colon vs controls (P < 0.05). Although dysregulations in stress-responsive systems such as the HPA axis and mucosal immune function are demonstrated in IBS, they do not appear to have a primary role in modulating IBS severity and abdominal pain. PMID:18684212

  20. Is the association between irritable bowel syndrome and abuse explained by neuroticism? A population based study

    PubMed Central

    Talley, N; Boyce, P; Jones, M

    1998-01-01

    Background—In outpatients and the community, an association between abuse (particularly sexual abuse) and irritable bowel syndrome (IBS) has been observed, but whether there is a causal link continues to be disputed. 
Aims—To test the hypothesis that psychological factors explain the apparent association between abuse and IBS. 
Methods—A sample of residents of Penrith (a Sydney suburb sociodemographically similar to the Australian population) selected randomly from the electoral rolls (that by law include the entire population of age 18 years and above) was mailed a validated self report questionnaire. Measured were gastrointestinal (GI) symptoms including the Rome criteria for IBS, abuse (including the standardised Drossman questions), neuroticism (Eysenck Personality Questionnaire), and psychological morbidity (General Health Questionnaire). 
Results—The response rate was 64% (n=730); 12% fulfilled the Rome criteria for IBS. Overall abuse in childhood (odds ratio (OR)=2.02, 95% confidence interval (CI) 1.29 to 3.15) but not adulthood (OR=1.39, 95% CI 0.88 to 2.19) was associazted with IBS univariately. Neuroticism and psychological morbidity were also univariately associated with abuse in childhood, abuse in adulthood, and IBS, respectively. However, by logistic regression, abuse in childhood was not associated with IBS after controlling for age, gender, and psychological factors (OR=1.34, 95% CI 0.83to 2.17). The results were not altered by restricting the analyses to more severe forms of abuse, and were not explained by interactions between abuse and psychological variables. 
Conclusion—There is an association between abuse and IBS in the community, but this may be explained in part by other psychological factors. Based on a path analysis, we postulate that abuse may induce the expression of neuroticism that in turn leads to IBS. 

 Keywords: epidemiology; irritable bowel syndrome; abuse; neuroticism PMID:9505885