Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sodium-coupled transporters are ubiquitous pumps that harness pre-existing sodium gradients to catalyse the thermodynamically unfavourable uptake of essential nutrients, neurotransmitters and inorganic ions across the lipid bilayer. Dysfunction of these integral membrane proteins has been implicated in glucose/galactose malabsorption, congenital hypothyroidism, Bartter's syndrome, epilepsy, depression, autism and obsessive-compulsive disorder. Sodium-coupled transporters are blocked by a number of therapeutically important compounds, including diuretics, anticonvulsants and antidepressants, many of which have also become indispensable tools in biochemical experiments designed to probe antagonist binding sites and to elucidate transport mechanisms. Steady-state kinetic data have revealed that both competitive and noncompetitive modes of inhibition exist. Antagonist dissociation experiments on the serotonin transporter (SERT) have also unveiled the existence of a low-affinity allosteric site that slows the dissociation of inhibitors from a separate high-affinity site. Despite these strides, atomic-level insights into inhibitor action have remained elusive. Here we screen a panel of molecules for their ability to inhibit LeuT, a prokaryotic homologue of mammalian neurotransmitter sodium symporters, and show that the tricyclic antidepressant (TCA) clomipramine noncompetitively inhibits substrate uptake. Cocrystal structures show that clomipramine, along with two other TCAs, binds in an extracellular-facing vestibule about 11 A above the substrate and two sodium ions, apparently stabilizing the extracellular gate in a closed conformation. Off-rate assays establish that clomipramine reduces the rate at which leucine dissociates from LeuT and reinforce our contention that this TCA inhibits LeuT by slowing substrate release. Our results represent a molecular view into noncompetitive inhibition of a sodium-coupled transporter and define principles for the rational design of new inhibitors.
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PMID:Antidepressant binding site in a bacterial homologue of neurotransmitter transporters. 1768 33

Gluten-restricted diets have become increasingly popular among parents seeking treatment for children diagnosed with autism. Some of the reported response to celiac diets in children with autism may be related to amelioration of nutritional deficiency resulting from undiagnosed gluten sensitivity and consequent malabsorption. A case is presented of a 5-year-old boy diagnosed with severe autism at a specialty clinic for autistic spectrum disorders. After initial investigation suggested underlying celiac disease and varied nutrient deficiencies, a gluten-free diet was instituted along with dietary and supplemental measures to secure nutritional sufficiency. The patient's gastrointestinal symptoms rapidly resolved, and signs and symptoms suggestive of autism progressively abated. This case is an example of a common malabsorption syndrome associated with central nervous system dysfunction and suggests that in some contexts, nutritional deficiency may be a determinant of developmental delay. It is recommended that all children with neurodevelopmental problems be assessed for nutritional deficiency and malabsorption syndromes.
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PMID:Celiac disease presenting as autism. 1956 47

The medical understanding of autism has changed since it was first defined by Kanner. Nowadays medicine identifies many medical abnormalities and diseases, which may underline or aggravate the cognitive aspect, behavioural issues and general health in autists. This includes chronic inflammation of gastrointestinal tract, dysbiosis, maldigestion, malabsorption, malnutrition, food intolerance, allergies, chronic viral, fungal and bacterial infections, impaired kidney function, impaired detoxification of endo- and exotoxins, disorders of metal ion transportation. Treatment of the above mentioned conditions combined with improving detoxification mechanisms, followed by a special diet and individually customized supplementation of nutritional deficiencies may lead to the improvement of the functioning of these patients, changing their level of functioning and self-dependence. The aim of this paper is to present medical problems of children with autism which may be identified and treated by general practitioners as a review of current medical papers related to Autism Spectrum Disorder, in the context of author's professional experience, based on the medical cases from author's practice.
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PMID:The review of most frequently occurring medical disorders related to aetiology of autism and the methods of treatment. 2062 38

Normal functioning of the human body requires a balance between nutritional intake and metabolism, and imbalances manifest as nutritional deficiencies or excess. Nutritional deficiency states are associated with social factors (war, poverty, famine, and food fads), medical illnesses with malabsorption (such as Crohn disease, cystic fibrosis, and after bariatric surgery), psychiatric illnesses (eating disorders, autism, alcoholism), and medications. Nutritional excess states result from inadvertent or intentional excessive intake. Cutaneous manifestations of nutritional imbalance can herald other systemic manifestations. This contribution discusses nutritional deficiency and excess syndromes with cutaneous manifestations of particular interest to clinical dermatologists.
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PMID:Syndromes associated with nutritional deficiency and excess. 2103 91

Autism spectrum disorders (ASDs) are characterized by deficits in the individual's ability to socialize, communicate, and use the imagination, in addition to stereotyped behaviors. These disorders have a heterogenous phenotype, both in relation to symptoms and regarding severity. Organic problems related to the gastrointestinal tract are often associated with ASD, including dysbiosis, inflammatory bowel disease, exocrine pancreatic insufficiency, celiac disease, indigestion, malabsorption, food intolerance, and food allergies, leading to vitamin deficiencies and malnutrition. In an attempt to explain the pathophysiology involved in autism, a theory founded on opioid excess has been the focus of various investigations, since it partially explains the symptomatology of the disorder. Another hypothesis has been put forward whereby the probable triggers of ASDs would be related to the presence of bacteria in the bowel, oxidative stress, and intestinal permeability. The present update reviews these hypotheses.
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PMID:Opioid peptides and gastrointestinal symptoms in autism spectrum disorders. 2730 56

Following a gluten-free diet is recommended by clinical guidelines in the presence of gluten intolerance. However, due to the variety of clinical picture of various forms of intolerance, the elimination of gluten occurs not always timely. There are also diseases that classic treatment regimen does not include diet therapy, however, studies have confirmed the effectiveness of its use. The aim of the research - to study current data on the effectiveness of a gluten-free diet for extra-intestinal manifestations of gluten intolerance. Material and methods. Literature data concerning the effectiveness of including a gluten-free diet in the treatment of various diseases according to the PubMed and eLIBRARY portal were studied. Results. Modern data on the forms of gluten intolerance and their clinical manifestations are presented. The results of both randomized studies and individual clinical cases of gluten intolerance that occurred under the guise of other diseases are presented. A clinical case of an acute onset of the disease - celiac crisis, accompanied by acute diarrheal syndrome with subsequent malabsorption and progressive loss of body weight, anasarca and electrolyte disorders is considered. Neurological and psycho-neurological manifestations of celiac disease are described, including current data on the results of including a glutenfree diet in the treatment of autism spectrum disorders. The question of using dietary therapy for autism remains controversial to nowadays. The article outlines the arguments of supporters and opponents of excluding gluten in this pathology. Particular attention is paid to the diagnosis of gluten intolerance in patients with hematological disorders. The significance of a complete survey to identify celiac disease and timely diet therapy of the disease under stunted growth in children, after excluding other causes of malabsorption and even in the presence of negative serological markers of celiac disease is shown. The article also contains information on the pathology of kidneys and reproductive system, which were leveled only after the exclusion of gluten from the diet. Conclusion. The presented cases demonstrate a wide variety of clinical forms of gluten intolerance, examples of diagnostic search and dynamics of the clinical picture with the timely appointment of a gluten-free diet are given.
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PMID:[Gluten-free diet in the treatment of extra-intestinal forms of gluten intolerance]. 3245 2

We present a case of an otherwise healthy 3-year-old child who presented with limping, bone pain, fatigue, and agitation. Differential diagnosis included an infection of the bone, malignancy, an inflammatory bone disease, and metabolic bone disease. Magnetic resonance imaging of the lower limbs and the spine was consistent with scurvy, and the diagnosis was confirmed by very low levels of vitamin C. Further history taking revealed a diet based entirely on dairy pudding, with no fruits or vegetables, and being a "picky eater" was the sole reason. Intravenous treatment with vitamin C led to full recovery. Previous reports of scurvy were in patients with other medical conditions, such as malabsorption, or behavioral conditions as in autism. This case demonstrates that scurvy, an almost forgotten condition from past centuries, can occur in otherwise healthy children and should raise awareness regarding the importance of a balanced diet and proper nutritional history taking. Following growth charts as the only screening tool for balanced and inclusive nutrition may not be sufficient.
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PMID:"What can you C in a limping child?" Scurvy in an otherwise healthy "picky eater". 3310 52