Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of serotonin 5-HT(4) receptors has been proposed as treatment for irritable bowel syndrome, a common, complex and distressing gastrointestinal disorder. Abnormal intestinal motility and sensitivity in irritable bowel syndrome patients can result in diarrhea, constipation, abdominal pain, bloating, headache and fatigue; these and other symptoms can lead to exacerbation of psychological stress, which may in turn induce further physiological abnormalities and patient discomfort. The serotonin agonist tegaserod binds with high affinity to 5-HT(4) receptors and has demonstrated potent pharmacological effects on the mid- and distal gut. Tegaserod has been safely employed in clinical trials where it has demonstrated efficacy in normalizing intestinal function, thereby improving irritable bowel syndrome symptoms.
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PMID:Tegaserod: a serotonin 5-HT4 receptor agonist for treatment of constipation-predominant irritable bowel syndrome. 1564 12

After returning from the Beagle in 1836, Charles Darwin suffered for over 40 years from long bouts of vomiting, gut pain, headaches, severe tiredness, skin problems, and depression. Twenty doctors failed to treat him. Many books and papers have explained Darwin's mystery illness as organic or psychosomatic, including arsenic poisoning, Chagas' disease, multiple allergy, hypochondria, or bereavement syndrome. None stand up to full scrutiny. His medical history shows he had an organic problem, exacerbated by depression. Here we show that all Darwin's symptoms match systemic lactose intolerance. Vomiting and gut problems showed up two to three hours after a meal, the time it takes for lactose to reach the large intestine. His family history shows a major inherited component, as with genetically predisposed hypolactasia. Darwin only got better when, by chance, he stopped taking milk and cream. Darwin's illness highlights something else he missed--the importance of lactose in mammalian and human evolution.
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PMID:Darwin's illness revealed. 1581 89

Primary gastrointestinal non-Hodgkin lymphoma accounts for 13-18% of all malignant tumours of small bowel and only 1 % of large bowel tumours (1). Multiple lymphomatous polyposis is a rare entity, characterized by the presence of multiple lymphomatous polyps along the gut (2). Majority of cases with gastrointestinal primary lymphoma are classified histologically as "mantle cell" lymphomas. A 59 year old patient was admitted to our clinic for fatigue and rectal bleeding. Endoscopic examination of the colon revealed an infiltrative-exulcerative lesion of the terminal ileon, a polypoid mass on ileocecal valve and multiple polyps over the entire colon and rectum. Gastroscopy revealed polyps into the duodenal bulb. Histopathological and immunohistochemical studies on biopsy specimens from colon and duodenum confirmed gastrointestinal non-Hodgkin lymphoma, probably "mantle cell" lymphoma. Because she was in an advanced stage she received only cytostatic treatment. A clinical, endoscopical and histopathological follow up at 3, 6 and 12 months was performed.
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PMID:Gastrointestinal lymphomatous polyposis--clinical, endoscopical and evolution features. A case report. 1620 Feb 39

Disorders such as chronic fatigue syndrome (CFS) and gulf war syndrome (GWS) are characterised by prolonged fatigue and a range of debilitating symptoms of pain, intellectual and emotional impairment, chemical sensitivities and immunological dysfunction. Sudden infant death syndrome (SIDS) surprisingly may have certain features in common with these conditions. Post-infection sequelae may be possible contributing factors although ongoing infection is unproven. Immunological aberration may prove to be associated with certain vasoactive neuropeptides (VN) in the context of molecular mimicry, inappropriate immunological memory and autoimmunity. Adenylate cyclase-activating VNs including pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) act as hormones, neurotransmitters, neuroregulators, immune modulators and neurotrophic substances. They and their receptors are potentially immunogenic. VNs are widely distributed in the body particularly in the central and peripheral nervous systems and have been identified in the gut, adrenal gland, blood cells, reproductive system, lung, heart and other tissues. They have a vital role in maintaining cardio-respiratory function, thermoregulation, memory, concentration and executive functions such as emotional responses including social cues and appropriate behaviour. They are co-transmitters for a number of neurotransmitters including acetylcholine and gaseous transmitters, are potent immune regulators with primarily anti-inflammatory activity, and have a significant role in protection of the nervous system against toxic assault as well as being important in the maintenance of homeostasis. This paper describes a biologically plausible mechanism for the development of certain fatigue-related syndromes based on loss of immunological tolerance to these VNs or their receptors following infection, other events or de novo resulting in significant pathophysiology possibly mediated via CpG fragments and heat shock (stress) proteins. These conditions extend the public health context of autoimmunity and VN dysregulation and have implications for military medicine where radiological, biological and chemical agents may have a role in pathogenesis. Possible treatment and prevention options are considered.
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PMID:Postulated vasoactive neuropeptide autoimmunity in fatigue-related conditions: a brief review and hypothesis. 1660 42

There is now evidence that chronic fatigue syndrome (CFS) is accompanied by immune disorders and by increased oxidative stress. The present study has been designed in order to examine the serum concentrations of IgA and IgM to LPS of gram-negative enterobacteria, i.e. Hafnia alvei; Pseudomonas aeruginosa, Morganella morganii, Proteus mirabilis, Pseudomonas putida, Citrobacter koseri, and Klebsiella pneumoniae in CFS patients, patients with partial CFS and normal controls. We found that the prevalences and median values for serum IgA against the LPS of enterobacteria are significantly greater in patients with CFS than in normal volunteers and patients with partial CFS. Serum IgA levels were significantly correlated to the severity of illness, as measured by the FibroFatigue scale and to symptoms, such as irritable bowel, muscular tension, fatigue, concentration difficulties, and failing memory. The results show that enterobacteria are involved in the etiology of CFS and that an increased gut-intestinal permeability has caused an immune response to the LPS of gram-negative enterobacteria. It is suggested that all patients with CFS should be checked by means of the IgA panel used in the present study and accordingly should be treated for increased gut permeability.
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PMID:Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. 1700 34

Obesity is associated with a decrease in energy expenditure relative to energy intake. The decrease in physical activity associated with obesity in several species, including humans, contributes to decreased energy expenditure. Several hormones and neuropeptides that affect appetite also modulate physical activity, including neuromedin U (NMU), a peptide found in the gut and brain. We have demonstrated that NMU microinjected into the hypothalamic paraventricular nucleus (PVN) in rats increases the energy expenditure associated with physical activity, called non-exercise activity thermogenesis (NEAT). Here we examined whether obesity in rats is related to decreased sensitivity of the PVN to the locomotor-activating effect of NMU. Diet-induced obese (DIO) rats and lean, diet-resistant (DR) rats were given PVN microinjections of increasing doses of NMU both before and after 1 month on a high-fat diet. We found that NMU increases physical activity, energy expenditure, and NEAT in a dose-dependent manner in both DR and DIO rats, both before and after 1 month on the high-fat diet. Before high-fat feeding, the obesity-prone and lean rats showed similar levels of physical activity after intra-PVN microinjections of NMU. After 1 month of the high-fat diet, however, the obesity-resistant rats showed significantly more NMU-induced physical activity compared to the obese DIO rats. Taken together with previous studies, these results suggest that obesity may represent a state associated with decreased central sensitivity to neuropeptides such as NMU that increase physical activity and therefore energy expenditure.
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PMID:Sensitivity of the hypothalamic paraventricular nucleus to the locomotor-activating effects of neuromedin U in obesity. 1770 46

During disease, infection, or trauma, the cytokine tumor necrosis factor alpha (TNF alpha) causes fever, fatigue, malaise, allodynia, anorexia, gastric stasis associated with nausea, and emesis via interactions with the central nervous system. Our studies have focused on how TNF alpha produces a profound gastric stasis by acting on vago-vagal reflex circuits in the brainstem. Sensory elements of this circuit (i.e., nucleus of the solitary tract [NST] and area postrema) are activated by TNF alpha. In response, the efferent elements (i.e., dorsal motor neurons of the vagus) cause gastroinhibition via their action on the gastric enteric plexus. We find that TNF alpha presynaptically modulates the release of glutamate from primary vagal afferents to the NST and can amplify vagal afferent responsiveness by sensitizing presynaptic intracellular calcium-release mechanisms. The constitutive presence of TNF alpha receptors on these afferents and their ability to amplify afferent signals may explain how TNF alpha can completely disrupt autonomic control of the gut.
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PMID:TNFalpha: a trigger of autonomic dysfunction. 1791 Dec 24

There is now evidence that major depression (MDD) is accompanied by an activation of the inflammatory response system (IRS) and that pro-inflammatory cytokines and lipopolysacharide (LPS) may induce depressive symptoms. The aim of the present study was to examine whether an increased gastrointestinal permeability with an increased translocation of LPS from gram negative bacteria may play a role in the pathophysiology of MDD. Toward this end, the present study examines the serum concentrations of IgM and IgA against LPS of the gram-negative enterobacteria, Hafnia Alvei, Pseudomonas Aeruginosa, Morganella Morganii, Pseudomonas Putida, Citrobacter Koseri, and Klebsielle Pneumoniae in MDD patients and normal controls. We found that the prevalences and median values for serum IgM and IgA against LPS of enterobacteria are significantly greater in patients with MDD than in normal volunteers. These differences are significant to the extent that a significant diagnostic performance is obtained, i.e. the area under the ROC curve is 90.1%. The symptom profiles of increased IgM and IgA levels are fatigue, autonomic and gastro-intestinal symptoms and a subjective feeling of infection. The results show that intestinal mucosal dysfunction characterized by an increased translocation of gram-negative bacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. It is suggested that the increased LPS translocation may mount an immune response and thus IRS activation in some patients with MDD and may induce specific "sickness behaviour" symptoms. It is suggested that patients with MDD should be checked for leaky gut by means of the IgM and IgA panel used in the present study and accordingly should be treated for leaky gut.
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PMID:The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. 1828 40

Although giardiasis is considered by most medical practitioners to be an easily treated infection, prolonged symptoms due to, or following, Giardia duodenalis infection can have a significant impact on quality of life. Symptom recurrence, including abdominal symptoms and fatigue, can result from re-infection, treatment failure, disturbances in the gut mucosa or post-infection syndromes. In developed countries, these sequelae can have an enormous impact on quality of life; in developing countries, particularly in children, they add yet another burden to populations that are already disadvantaged. Here, we outline current knowledge, based on individual case sequelae from sporadic infections, observations of population effects following outbreaks and studies of phenotypic and genotypic diversity between morphologically identical isolates of parasites. We also raise further questions, looking for clues as to why giardiasis sometimes becomes an intrusive, long-term problem.
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PMID:Giardiasis--why do the symptoms sometimes never stop? 2005 86

Central to obesity is an energy imbalance due to increased calorie intake and/or decreased energy expenditure, as well as a genetic or non genetic biological predisposition. New advances in obesity research point to a role of primary changes in fat storage capacity. Modifications of the cellular composition and structure of adipose tissue, characterized by inflammation and fibrosis, can lead to an "organ disease" that is partially irreversible, thus explaining long-term treatment resistance. This organ disease may lead to local and systemic disorders. A possible role of the gut flora is one especially interesting line of research.
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PMID:[New insights into obesity]. 2012 Jan 57


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