Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ileal prostaglandin (PGs) biosynthesis was compared in female rats in normal mild hemorrhage (exposed to mild hypotension, reperfusion, and maintenance on hyperalimentation for 5 days) and control groups (instrumentation and hyperalimentation without hemorrhage). Tissue PG levels were analyzed by radiochromatographic analysis of microsomal membrane fractions prepared from the ileum in each group. Total cyclooxygenase activity in the normal and control groups was modest, with low levels of 6-keto-PGF1 alpha, PGE2, PGF2 alpha, thromboxane B2, PGA2, and PGD2 being produced. Hemorrhage, reperfusion, and maintenance on hyperalimentation for 5 days markedly induced total cyclooxygenase activity in the female rat ileum. Ileal microsomal membrane fractions obtained from the mild hemorrhage group synthesized levels of individual PGs three- to seven-fold higher than the normal or control groups, with 6-keto- PGF1 alpha (breakdown product of prostacyclin), PGE2, and PGA2 demonstrating the highest levels of biosynthesis. These data suggest that the gastrointestinal tract could serve as a source for the elevated PGs known to occur in various shock models.
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PMID:Elevated PGI2 and PGE2 production in the rat ileum following mild hypotension. 313 63

Intestinal mucosa and muscularis/serosa prostaglandin (PG) biosynthesis was compared in sham control female rats and rats subjected to mild hemorrhage (hemorrhage to 80 mm Hg for 60 min), blood reperfusion, and maintenance on hyperalimentation (TPN) for 5 days. Tissue PG synthesis was analyzed by radiochromatographic analysis of microsomal membrane fractions prepared from mucosa and muscularis/serosa removed from the duodenum, jejunum, and ileum. Individual PG synthesis in the mucosa and muscularis/serosa sham group was modest, with low levels of synthesis of 6-keto-PGF1 alpha, PGE2, PGF2 alpha, and thromboxane B2. Hemorrhage, reperfusion, and maintenance on TPN for 5 days did not alter PG synthesis in the mucosa, whereas muscularis/serosa synthesis of 6-keto-PGF1 alpha and PGE2 was increased five-fold or more in each tissue studied. These data suggested that the muscularis/serosa could serve as a major source for the elevated PG, previously shown to occur following long-term resuscitation after acute hemorrhage.
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PMID:Long-term hyperalimentation following hemorrhage/reperfusion injury induces intestinal prostanoid synthesis. 850 20

Despite recent advances in antibiotic therapy, aggressive operative intervention and intravenous hyperalimentation, sepsis, and multiple organ failure are still reported to contribute to significant morbidity and mortality in the surgical intensive care unit. In light of this, it is essential to determine the mechanism underlying the pathophysiology of sepsis so that better therapeutic interventions can be designed. Experimental studies indicate that murine polymicrobial sepsis induces a marked suppression in both lymphocytic and macrophage function associated with decreased cellular adenosine triphosphate levels and increased Ca2+. However, such changes are not detectable until approximately 12 h after the onset of sepsis. Alternatively, early (0-4 h) in sepsis, macrophages from the liver and peritoneum exhibit augmented innate secretion of proinflammatory cytokines, tumor necrosis factor, interleukin (IL)-6, and IL-1, associated with the systemic release of these agents. Sustained release of immunosuppressive agents transforming growth factor-beta, IL-4, IL-10, and PGE2, as well as glucocorticoids, are also observed during sepsis. In this regard, many investigators, including us, have suggested that an agent(s) released as a part of this systemic inflammatory response to sepsis may be responsible for the protracted suppression of immune cell function. Studies examining the effects of these mediators in vitro on various immune cells have shown that many of these agents also have the capacity to induce a process referred to as programmed cell death (PCD) or apoptosis (Ao). We have presented evidence of marked changes in the rate of Ao in immune cells after the onset of sepsis. These data suggest the possibility that mediators released in response to septic insult contribute to the observed changes in immune cell function through the induction of Ao. Inasmuch, understanding the contribution of PCD to the pathophysiology of sepsis, should provide a better basis from which to develop more effective therapy for the septic patient.
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PMID:Immune dysfunction in murine polymicrobial sepsis: mediators, macrophages, lymphocytes and apoptosis. 882 95

This study examines the hypothesis that long-term resuscitation with hyperalimentation (TPN) following acute hemorrhage/reperfusion (H/R) injury stimulates renal release of PGE2. Male Sprague-Dawley rats were anesthetized and subjected to sham or hemorrhage to 30 mmHg for 30 min followed by reperfusion. All rats were placed on TPN for 5 days, then underwent laparotomy for in vivo renal artery and aortic blood flow for 60 min. The kidney was perfused in vitro with Krebs-Henseleit buffer at 3 ml/min (pH 7.4, 37 degrees C) and venous effluent was collected for analysis of PGE2, 6-keto-PGF1 alpha and thromboxane B2 by EIA. Hemorrhage/reperfusion followed by TPN for 5 days increased renal PGE2 2-fold and decreased in vivo renal artery blood flow by 50% compared to the sham group. Hemorrhage/reperfusion followed by TPN did not alter release of the other eicosanoids measured. These data suggest that the kidney has a limited capacity to maintain renal blood flow by increasing release of PGE2 when the animal is subjected to long-term resuscitation with TPN following mild hemorrhage/reperfusion injury.
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PMID:Long-term resuscitation of hemorrhage/reperfusion injury (H/R) stimulates renal PGE2 release. 883 62

Obesity is a complex syndrome that involves defective signaling by a number of different factors that regulate appetite and energy homeostasis. Treatment with exogenous leptin reverses hyperphagia and obesity in ob/ob mice, which have a mutation that causes leptin deficiency, proving the importance of this factor and its receptors in the obesity syndrome. Cells with leptin receptors have been identified outside of the appetite regulatory centers in the brain. Thus leptin has peripheral targets. Because macrophages express signaling-competent leptin receptors, these cells may be altered during chronic leptin deficiency. Consistent with this concept, the present study identifies several phenotypic abnormalities in macrophages from ob/ob mice, including decreased steady-state levels of uncoupling protein-2 mRNA, increased mitochondrial production of superoxide and hydrogen peroxide, constitutive activation of CCAAT enhancer binding protein (C/EBP)-beta, an oxidant-sensitive transcription factor, increased expression of interleukin-6 and cyclooxygenase (COX)-2, two C/EBP-beta target genes, and increased COX-2-dependent production of PGE2. Given the importance of macrophages in the general regulation of inflammation and immunity, these alterations in macrophage function may contribute to obesity-related pathophysiology.
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PMID:Phenotypic abnormalities in macrophages from leptin-deficient, obese mice. 995 Jul 66