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)

Patients with head injury must overcome central as well as peripheral metabolic insults. In addition to specific tissue damage to the brain, a cellular biochemical cascade occurs that can negatively affect organ function, cause a systemic response to injury, and may cause secondary tissue injury. The metabolites involved in this cascade are numerous and complex. Cytokines are important cell-to-cell communication mediators during injury. It is speculated that cytokines, such as interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor (TNF), and interleukin 8 (IL-8), which are found in elevated amounts in both human and basic trials after head injury, play a role in the cellular cascade of injury. Some of the metabolic events produced by small doses of cytokine infusion in animals, as well as humans, include fever, neutrophilia, muscle breakdown, altered amino acid metabolism, depression of serum zinc levels, production of hepatic acute phase reactants, increased endothelial permeability, and expression of endothelial adhesion molecules. These are all known sequelae of severe head injury. Cytokines have also been implicated in organ failure. Infusion of cytokines in basic science trials revealed that organ functions of the gut, liver, and lung are negatively altered by high-dose cytokine infusion. Infusion of certain cytokines has been shown to cause death of brain cells, increase blood-brain barrier permeability, and cause cerebral edema. This suggests that cytokines may also play a role in the sequelae of organ demise. These effects of cytokines have been attenuated in basic trials by blocking the initial signaling system of cytokines or by decreasing serum cytokine activity. We hypothesize that cytokines that are elevated after head injury play a role in the pathology of injury, including altered metabolism and organ demise.
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PMID:Cytokines and metabolic dysfunction after severe head injury. 786 40

The family of Na(+)- and Cl(-)-dependent, 12 transmembrane domain transporter proteins now includes transporters for neurotransmitter molecules in the brain and for substances important in extraneuronal tissues, including adrenal, kidney, and gut. Transported substrates include monoamine and amino acid neurotransmitters and nonperturbing osmolytes. A common protein topology is predicted and features intracellular N- and C-termini possessing phosphorylation sites and at least one large extramembranous loop with N-linked glycosylation. Using the rat dopamine transporter as a template, molecular modeling of putative transmembrane domains coupled with amino acid sequence conservation analysis indicates amino acid residues potentially involved in substrate and/or ion recognition. Targeting such residues with site-directed mutagenesis will help clarify substrate and ion binding sites and should facilitate rational design of therapeutics to combat depression, locomotor disorders, and substance abuse.
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PMID:Sodium- and chloride-dependent transporters in brain, kidney, and gut: lessons from complementary DNA cloning and structure-function studies. 792 16

The double bath method has been used to study reflex inhibition of cholinergic transmission in the guinea-pig ileum segment. It is shown that adenosine, noradrenaline, 5-methylfurmethide as well as acute hypoxia, which affect the oral part of the intestine are able to evoke two kinds of effects in its anal part firstly, the depression of cholinergic transmission, and secondly, the stimulation of non-adrenergic, non-cholinergic contractions. A preliminary treatment with capsaicin and with hexamethonium on the oral part of the gut prevents these effects, and the chymotrypsin abolishes these effects. A mechanism of this reflex descending inhibition of cholinergic transmission is realised apparently through the stimulation of the chemoreceptors in afferent capsaicin-sensitive nerves with participation of cholinergic interneurons and activation of the inhibitory, most probably vasoactive intestinal peptidergic (VIP) neurons in the enteric plexuses.
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PMID:[The role of the chemosensory systems in the inhibitory regulation of cholinergic transmission in the small intestine]. 810 96

Corticotropin-releasing hormone (CRH), one of the primary regulators of the hypothalamic-pituitary-adrenal (HPA) axis, exhibits abnormal regulation in pathologic states such as depression and anorexia nervosa. Analysis of the role of CRH in regulation of the HPA axis would be facilitated by the creation of animal models in which CRH gene structure and function could be manipulated. We have determined the DNA sequence of the mouse CRH gene. Using a highly sensitive reverse transcription-polymerase chain reaction method, we have found expression of CRH mRNA in adrenal, ovary, testis, gut, heart, anterior pituitary, lung, and spleen, in addition to cerebral cortex and hypothalamus. Within the spleen, CRH mRNA is localized specifically to T-lymphocytes. We mapped the chromosomal location of mouse CRH via interspecific mouse backcrosses to chromosome 3, which is not the site of any naturally occurring mutations consistent with CRH deficiency. Because of this, we inactivated a CRH allele in mouse embryonic stem (ES) cells by homologous recombination with a mutant mouse CRH gene lacking the entire coding region of preproCRH. Mice chimeric for each of two ES clones with an inactivated CRH allele are being used to generate animals with complete CRH deficiency.
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PMID:Expression of the mouse corticotropin-releasing hormone gene in vivo and targeted inactivation in embryonic stem cells. 818 38

The effects of transgalactosylated disaccharide (TD) intake on human fecal microflora and their metabolism were investigated in 12 Japanese males. TD is a mixture of sugars, galactosyl galactose, and galactosyl glucose, synthesized from lactose through the transgalactosylation reaction of Streptococcus thermophilus beta-galactosidase. Volunteers took 15 g of the test sugar daily for 6 days. The TD ingestion increased the number of bifidobacteria and lactobacilli, but decreased the number of Bacteroidaceae and Candida spp. in the feces. The ratio of bifidobacteria to total bacteria increased from 0.28 to 0.51. TD decreased the fecal concentrations of propionic acid, isobutyric acid, isovaleric acid, and valeric acid. This sugar also lowered the fecal pH, and the concentrations of fecal ammonia, p-cresol, and indole. Moreover, a positive correlation was found between the concentration of ammonia, and that of branched-chain fatty acids (isobutyric acid and isovaleric acid), p-cresol, and indole. All of these compounds are produced from amino acids through deamination by the intestinal bacteria. The depression of amino acid fermentation by intestinal bacteria may be involved in the reduction of fecal ammonia. These results suggest that a part of the transgalactosylated disaccharides passes into the colon, inducing changes in the colonic microflora composition, hastening carbohydrate fermentation, and depressing amino acid fermentation in the human gut.
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PMID:Effects of transgalactosylated disaccharides on the human intestinal microflora and their metabolism. 822 19

Lymphatic drainage from the wall of the distal small intestine, important especially in young sheep as a major site of gut-associated lymphoid tissue, begins with a series of longitudinally oriented subserosal vessels. These vessels convey lymph to the mesenteric border of the intestinal wall and unite to form larger vessels which course through the mesentery to the mesenteric lymph nodes. These nodes lie towards the periphery of a broad, fan-shaped mesentery, adjacent to major arteries and veins. Mesenteric vessels convey lymph from the jejunum and part of the proximal ileum to the jejunal nodes. Lymph from most of the ileum is conveyed to caecal nodes. The larger mesenteric lymphatics have well formed smooth muscle and connective tissue layers surrounding the endothelium. They are often adjacent to, but rarely within, the connective tissue band anchoring the major arteries and veins to one or both lamellae of mesentery. Few anastomoses occur between vessels from opposing sides of the gut wall or the mesentery. Afferent lymphatics enter the subcapsular and trabecular sinuses of the nodes over most surfaces apart from the hilar region. Lymph flows through cortical tissue to the medulla, which occupies most of the node. In the medulla, sinuses occur within medullary cords as well as between them. Initial efferent lymphatics occur throughout medullary tissue. Efferent vessels emerge at a hilus then coalesce and drain into the jejunal or ileal trunk. The hilus of the node varies from a flat, poorly defined area on the lesser curvature, to a depression or groove. The latter commonly occurs in elongated jejunal nodes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lymphatic drainage from the distal small intestine in sheep. 827 Apr 68

Mesenteric hypoperfusion may be responsible for alterations in gut mucosa leading to necrotizing enterocolitis. Platelet-activating factor (PAF) and cocaine have been implicated in the etiology of necrotizing enterocolitis. We have demonstrated direct toxic effects of these compounds in vitro, but the in vivo mechanism of bowel damage is unknown. Newborn piglets (3.0 +/- 0.3 kg) had physiologic parameters (electrocardiogram, blood pressure, pulse, and central venous pressure) continuously monitored as well as Doppler probe recordings of superior mesenteric artery flow (Qsma). Aortic flow with calculation of cardiac index, and systemic and mesenteric vascular resistances (SVR and MVR) were also determined. Group 1 (N = 8) received PAF (0.5 microgram/kg). Groups 2 (N = 8) and 3 (N = 8) received high (17 mg/kg) and low (9 mg/kg) doses of cocaine, respectively. Each subject served as its own control. Histology demonstrated edema or early mucosal hemorrhage in all groups. PAF caused a third-degree atrioventricular block of short duration and a prolonged decrease of the cardiac index, but only a brief elevation of SVR and MVR. The cocaine groups had a sustained increase of SVR and MVR associated with a decrease of cardiac index. The decrease of Qsma paralleled the changes of MVR in each subject. These data show that both PAF and cocaine induce mesenteric ischemia. The effect of PAF is of short duration and mainly related to its cardiotoxic effects resulting in low Qsma. Cocaine causes an increase in MVR with prolonged depression of mesenteric flow.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Systemic and mesenteric vascular effects of platelet-activating factor and cocaine. In vivo effects on a neonatal swine model. 848 Sep 32

Although recent studies have shown that gut absorptive function is significantly depressed even in the early hyperdynamic phase of sepsis, the mechanism responsible for this is unknown. Tumor necrosis factor (TNF-alpha) is a potent mediator of shock resulting in a marked inflammatory response leading to mucosal erosions of the gut and multiple organ failure. Although TNF is elevated in early sepsis, it remains unknown whether TNF plays any role in the depression of gut absorptive function under these conditions. To study this, we used the 1 hr D-xylose absorption test. C3H/HeN mice (n = 12) were lightly anesthetized, and a femoral artery and the portal vein were cannulated. After recovery from anesthesia, 125 micrograms recombinant murine TNF-alpha (rMuTNF-alpha)/kg body weight was given via the tail vein to one group of animals, while another group received an equivalent volume of saline (sham). One hour later, D-xylose was given orally. The systemic blood pressure was recorded 1 hr thereafter and D-xylose concentration in a sample of portal blood was determined colorimetrically. Results show that, while the systemic pressure was elevated 2 hr after administration of rMuTNF-alpha, D-xylose absorption was severely depressed. Thus the depressed gut absorptive function seen in the early stage of sepsis may be mediated directly or indirectly by TNF-alpha.
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PMID:Tumor necrosis factor depresses gut absorptive function. 848 19

Kupffer cells (KC) and gut-derived bacterial endotoxin have been implicated in the aetiology of alcoholic liver disease. Using in vivo microscopic methods, we have shown that ethanol ingestion in mice causes a dose dependent increase in leucocyte adhesion and endothelial cell swelling in hepatic sinusoids. Activation of KC is elicited at low doses while depression occurs at high doses and with chronic exposure. The responses are exacerbated in the presence of endotoxaemia or sepsis and are not seen in endotoxin-resistant animals, implicating a role for endotoxin in the ethanol-induced inflammatory response. In addition, the responses are abolished with anti-TNF alpha suggesting that TNF alpha is a primary mediator of these events. Nitric oxide (NO) initially appears to play an important role in these events by stabilizing the TNF alpha-mediated hepatic microvascular inflammatory response to acute ethanol ingestion, thereby helping to protect the liver from ischaemia and leucocyte induced oxidative injury. Finally, an ongoing clinical study has confirmed a mild systemic endotoxaemia in patients hospitalized for alcoholic liver disease. All of these results support important roles for endotoxin, cytokines, nitric oxide and sinusoidal lining cells in the pathophysiology of liver injury resulting from ethanol alone or in combination with infection.
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PMID:Role of endotoxin in the hepatic microvascular inflammatory response to ethanol. 858 35

Rats of the Flinders sensitive line (FSL, selectively bred for their increased cholinergic activity and used as a genetic animal model of depression) were compared with their control counterparts, the Flinders resistant line, for their susceptibility to anaphylaxis and the response of small intestinal tissues to the muscarinic agonist, bethanechol. Following sensitization to ovalbumin (OA), rats of both lines were challenged in vivo either with 3 mg OA i.p. or with saline. In spite of the absence of line-related differences in IgE titers, FSL rats were more susceptible to the induction of anaphylactic shock as evidenced by (1) more pronounced mast cell degranulation; (2) a greater drop in rectal temperature; (3) higher hematocrit values; and (4) changes in gut function characterized by an elevation of basal short-circuit current and increased conductance (indicating increases in transport tone and permeability) of the tissues mounted in Ussing chambers. Thus, this study provides further evidence for a common cholinergic mechanisms in susceptibility to both allergies and depression.
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PMID:Immediate hypersensitivity in the Flinders rat: further evidence for a possible link between susceptibility to allergies and depression. 859 Aug 17


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