Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The irritable bowel syndrome (IBS) is a consortium of symptoms including abdominal pain and alterations in the pattern of defaecation. There is no single pathophysiological marker of IBS although it is generally accepted that some patients do have abnormalities of intestinal motility and/or enhanced visceral sensitivity. There is also an increasing acceptance that the central nervous system, an important component of the brain-gut axis, also plays an important role in symptom production both in the response to stress and when there is an underlying affective disorder. During the past decade new therapeutic targets have been identified that have permitted the development of new drugs with therapeutic potential for IBS. Identification and characterization of 5-hydroxytryptamine (5-HT) receptors in the gastrointestinal tract particularly 5-HT3 and 5-HT4 receptors, which are involved not only in modulating gut motility but in visceral sensory pathways, has led to a number of studies of 5-HT3 (Alosetron, Granisetron and Ondansetron) and 5-HT4 (SB-207266A) antagonists. Both classes of drug appear to reduce visceral sensitivity and have inhibitory effects on motor activity in the distal intestine. Early clinical studies suggest that these agents may have a role in painful, diarrhoea-predominant IBS. 5-HT4 agonists (HTF919, Zelmac) may improve constipation-predominant IBS by normalizing bowel habit and thereby reducing abdominal pain. Alternative approaches to reducing visceral sensation include the use of the opioid kappa agonists, which have no central opioid effects although clinical trials have suggested that these agents are not highly effective in relieving IBS pain. There are in addition, new approaches to modify intestinal motility including the development of gut selective muscarinic M3 receptor antagonists such as zamifenacin and the 5-HT4 partial agonist, HTF919. Preliminary studies suggest that these agents may have therapeutic potential in IBS. Anti-depressants are increasingly used to treat affective disorder in IBS but in addition appear to have added value because of their ability to reduce visceral hypersensitivity and alter gut transit. Therapeutic effects are often obtained at doses below those normally used to treat depression. IBS continues to be a therapeutic challenge because of its diverse symptomatology and lack of a single pathophysiological target for drug intervention.
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PMID:Irritable bowel syndrome: new pharmaceutical approaches to treatment. 1058 Sep 22

In 1970, Erspamer et al.(1,14)isolated and characterized the tetradecapeptide bombesin (BN) from the skin of amphibian frog Bombina bombina. Subsequently, several BN-like peptides have been identified in mammals, consisting of various forms of gastrin-releasing peptide (GRP) and/or neuromedin B (NMB), together with their distinct receptor subtypes. It has been proposed that BN-related peptides may be released from the gastrointestinal (GI)-tract in response to ingested food, and that they bridge the gut and brain (through neurocrine means) to inhibit further food intake. Conversely, the suppression of release of BN-like peptides at relevant brain nuclei may signal the initiation of a feeding episode. The present review will describe recent pharmacological, molecular, behavioral and physiological experiments, supporting the contention that endogenous BN-related peptides do indeed influence ingestive behaviors. Particular attention is focused on the relationship between these peptides in the peripheral compartment and their impact on central circuits using GRP and/or NMB as transmitters. In addition, however, we will point out various caveats and conundrums that preclude unequivocal conclusions about the precise role(s) of these peptides and their mechanism(s) of action. We conclude that BN-related peptides play an important role in the control of food intake, and may contribute to ingestive disruptions associated with anorexia (anorexia nervosa, AIDS and cancer anorexia), bulimia, obesity and depression. Hence, pharmacological targeting of these systems may be of therapeutic value.
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PMID:Role of bombesin-related peptides in the control of food intake. 1065 15

Polymerase chain reaction (PCR)-based genotyping of oocysts dissected from mosquito midguts has previously been used to investigate overall levels of inbreeding within malaria parasite populations. We present a re-analysis of the population structure of Plasmodium falciparum malaria using diploid genotypes at three antigen-encoding loci in 118 oocysts dissected from 34 mosquitoes. We use these data to ask whether mating is occurring at random within the mosquito midgut, as is generally assumed. We observe a highly significant deficit of heterozygous oocysts within mosquitoes at all three loci, suggesting that fusion of gametes occurs non-randomly in the mosquito gut. A variety of biological explanations, such as interrupted feeding of mosquitoes, positive assortative mating and outcrossing depression, could account for this observation. However, an alternative artefactual explanation--the presence of non-amplifying or null alleles--can account for the observed data equally well, without the need to invoke non-random mating. To evaluate this explanation further, we estimate the frequencies of null alleles within the oocyst population using maximum likelihood, by making the assumption that non-amplifying oocysts at any of the three loci are homozygous for null alleles. Observed levels of visible heterozygotes fit closely with those expected under random mating when non-amplifying oocysts are accounted for. Other lines of evidence also support the artefactual explanation. Overall inbreeding coefficients have been recalculated in the light of this analysis, and may be considerably lower than those estimated previously. In conclusion, we suggest that the deficit of heterozygotes observed is unlikely to indicate non-random mating within the mosquito gut and is better explained by misscoring of heterozygotes as homozygotes.
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PMID:Do malaria parasites mate non-randomly in the mosquito midgut? 1089 65

The vagus nerve may indirectly influence thermoregulation by modulation of energy balance: its afferent fibers convey signals that represent information on feeding state, resulting in either depression or stimulation of metabolic processes. A regulated metabolic depression can be detected in the background of fasting-induced hypometabolism and hypothermia. In its development (besides humoral signals) vagally transmitted neural signals of gastrointestinal and hepatoportal origin are important. These signals are related to hunger, to decrease of mechanical/chemical stimuli from the gut, to decline of blood glucose; they alter discharge rates of vagal afferents and activity of the nucleus of the solitary tract, eliciting inhibition of metabolic rate and enhancement of food intake. In this hunger-related metabolic inhibition the nucleus of the solitary tract is in interaction with hypothalamic nuclei, that contribute to neuropeptide changes characterized by high neuropeptide Y activity (with energy-conserving type of regulation) and depressed cholecystokinin and corticotropin releasing hormone activities (with depressed energy-expenditure). In postalimentary states the hypermetabolism and hyperthermia are due to opposite changes in metabolic regulation. Satiety-related stimulatory signals of abdominal origin, transmitted via hepatic vagal afferents to the nucleus of the solitary tract, contribute to enhancement of sympathetic activity and stress-responsiveness, leading to hypermetabolism and hyperthermia. Depressed neuropeptide Y release and enhanced cholecystokinin and corticotropin releasing hormone activities participate in the central regulatory changes, and in the high energy-expenditure. The biological role of these vagal functions is not directly the regulation of body temperature, rather the regulation of energy balance and energy content in the body.
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PMID:The vagus nerve in thermoregulation and energy metabolism. 1118 24

Hepatic encephalopathy is considered to be a reversible metabolic encephalopathy, which occurs as a complication of hepatocellular failure and is associated with increased portal-systemic shunting of gut-derived nitrogenous compounds. Its manifestations are most consistent with a global depression of CNS function, which could arise as a consequence of a net increase in inhibitory neurotransmission, due to an imbalance between the functional status of inhibitory (e.g., GABA) and excitatory (e.g., glutamate) neurotransmitter systems. In liver failure, factors that contribute to increased GABAergic tone include increased synaptic levels of GABA and increased brain levels of natural central benzodiazepine (BZ) receptor agonists. Ammonia, present in modestly elevated levels, may also augment GABAergic tone by direct interaction with the GABAA receptor, synergistic interactions with natural central BZ receptor agonists, and stimulation of astrocytic synthesis and release of neurosteroid agonists of the GABAA receptor. Thus, there is a rationale for therapies of HE that lower ammonia levels and incrementally reduce increased GABAergic tone towards the physiologic norm.
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PMID:Pathogenesis of hepatic encephalopathy. 1123 1

The metabolic response to critical illness promotes catabolism, which mobilizes substrates for energy. Initially the hypothalamic-pituitary-adrenal axis is stimulated, but later there appears to be anterior pituitary depression. Despite this, the early increase in plasma cortisol levels is usually maintained by means independent of (falling) corticotropin levels. Some patients, however, develop acute adrenal insufficiency and appear to benefit from replacement exogenous glucocorticoid. However, identifying such patients is often difficult. The replacement of other deficiencies may not be in the patients' interests. For example, leptin, a stress-related hormone, has multiple effects, some seemingly advantageous and others detrimental in critical illness. Its overall influence and significance remains unclear.The health of gut mucosa and the inflammatory response might be improved or influenced to the (presumed) benefit of the patient by agents such as glutamine, arginine, some eicosanoids, and exogenous nucleic acids. Such "immunonutrition" appears to improve mortality and other measures of outcome in surgical intensive care unit patients and those with sepsis.
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PMID:The metabolic and nutritional response to critical illness. 1132 6

Society, the workplace and the family are changing. Despite increasing wealth, these changes appear to be accompanied by increasing anxiety and depression. Functional bowel disorders are associated with increased psychological morbidity, and the treatment of functional disorders needs to take these social and psychological factors into account. In the medical setting, therefore, the "therapeutic team" needs to be restructured to encompass a broader spectrum of skills and resources than currently exists in most units. An increase in understanding of pathophysiological mechanisms is likely to be helpful for patients who are not amenable to, or have failed, first line psychologically based, or simple drug, therapies. For example, in reflux disease, the elucidation of the mechanism underlying spontaneous sphincter relaxations may lead to precise end organ targeting-this can be at efferent or afferent ends of the pathways. Recent elucidation of involvement of GABA and NO have highlighted possible neurochemical targets. In constipation 5-HT4 agonists have lead to specific activation of motor events responsible for gut transport. For diarrhoea, multiple targets are available. e.g. opioid agonists, somatostatin analogues. Modulation of pain represents a more difficult task. Decreasing visceral sensitivity, and alteration of cerebral or spinal mediation of pain, remain unproven strategies. Greater understanding of the mechanisms by which chronic stress influence gut function and symptoms is likely to lead to new therapeutic approaches. This should include an understanding of the link between psychological morbidity and altered autonomic effector function. It should help in understanding why symptoms localise to different body systems, such as the gut or gynaecological viscera. Other priorities in this area are to improve clinical trial design, and to improve symptom and quality of life measures of the efficacy of treatments.
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PMID:Challenges in functional bowel disease. 1171 21

Protein synthesis is severely depressed in hibernating mammals. In the absence of significant protein synthesis, the continued turnover of proteins as a function of normal cellular activity would result in the net depletion of protein pools. We measured levels of ubiquitylated proteins in the gut of thirteen-lined ground squirrels ( Spermophilus tridecemlineatus) and liver of golden-mantled ground squirrels ( Spermophilus lateralis). In both tissues, ubiquitin conjugate concentrations increased during entrance into torpor and were elevated 2-3 fold by late torpor compared with levels in active animals. The data are consistent with a depression of proteolysis with a resultant high level of ubiquitylated proteins during the natural hypothermia of torpor. The periodic returns to euthermy during the hibernation season allow for degradation of these conjugated proteins and may serve to restore protein pools.
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PMID:Ubiquitin conjugate dynamics in the gut and liver of hibernating ground squirrels. 1191 8

Major burn injury is a lesion where the inflammatory reaction is exported to the whole body. After a short time of hemodynamic changes, this inflammation is kept by necrotic tissues, persistence of an opened wound, and by the pulmonary and gut reactions. When infection starts, it becomes difficult to distinguish its symptoms among the inflammatory signals. The main point of the care of burn patient consists in trying to control this reaction and the immuno-depression it leads to: early excision and grafts, early enteral nutrition, perfect nursing care. There is no specific medical treatment of this state. The antibiotic use must be well weighed up. Infection is often the trigger of the multiple organ dysfunction which is the way the burn patient dies but is not mandatory.
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PMID:[Inflammatory reaction and infection in severe burns]. 1193 39

Poult enteritis and mortality syndrome (PEMS) has multiple etiological agents associated with its occurrence, including two viruses and at least three Escherichia coli isolates. Myco Curb (MC) contains organic acids and is used as a feed additive to inhibit growth of many bacteria and toxin-producing molds but not viruses. Studies evaluating the influence of MC on BW, feed conversion, and mortality indicate that turkey poults tolerate MC at 1.25% but not 2.50%, but higher MC content in feed provides greater suppression of growth of bacterial isolates commonly associated with PEMS. In two PEMS experiments, 1.25% MC was blended into poult starter feed and was maintained in the feed for the duration of the 3-wk experiments. In these experiments, 1-d-old commercial poults were placed into battery brooders and were given turkey starter feed and water ad libitum. At 6 d posthatch, PEMS-designated poults were given a 1-mL oral gavage of a 10% suspension of feces from PEMS-infected poults. BW depression due to PEMS was not alleviated by MC, although there was less variation in mean BW of the MC-fed poults, and there was a highly significant reduction in mortality (68% in PEMS-exposed with MC vs. 32.5% in PEMS-exposed without MC). The reduction in mortality in the MC-fed poults was attributed to decreased bacterial content of the gut and to maintenance of packed cell volume and hemoglobin content. It was concluded that MC might be a potential nutritional intervention during PEMS.
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PMID:Influence of a propionic acid feed additive on performance of turkey poults with experimentally induced poult enteritis and mortality syndrome. 1216 55


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