Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemotherapy and radiotherapy, whilst highly effective in the treatment of neoplasia, can also cause damage to healthy tissue. In particular, the alimentary tract may be badly affected. Severe inflammation, lesioning and ulceration can occur. Patients may experience intense pain, nausea and gastro-enteritis. They are also highly susceptible to infection. The disorder (mucositis) is a dose-limiting toxicity of therapy and affects around 500 000 patients world-wide annually. Oral and intestinal mucositis is multi-factorial in nature. The disruption or loss of rapidly dividing epithelial progenitor cells is a trigger for the onset of the disorder. However, the actual dysfunction that manifests and its severity and duration are greatly influenced by changes in other cell populations, immune responses and the effects of oral/gut flora. This complexity has hampered the development of effective palliative or preventative measures. Recent studies have concentrated on the use of bioactive/growth factors, hormones or interleukins to modify epithelial metabolism and reduce the susceptibility of the tract to mucositis. Some of these treatments appear to have considerable potential and are at present under clinical evaluation. This overview deals with the cellular changes and host responses that may lead to the development of mucositis of the oral cavity and gastrointestinal tract, and the potential of existing and novel palliative measures to limit or prevent the disorder. Presently available treatments do not prevent mucositis, but can limit its severity if used in combination. Poor oral health and existing epithelial damage predispose patients to mucositis. The elimination of dental problems or the minimization of existing damage to the alimentary tract, prior to the commencement of therapy, lowers their susceptibility. Measures that reduce the flora of the tract, before therapy, can also be helpful. Increased production of free radicals and the induction of inflammation are early events in the onset of mucositis. Prophylactic administration of scavengers or anti-inflammatories can partially counteract or limit some of these therapy-mediated effects, as can the use of cryotherapy. The regular use of mouthwashes, mouth coatings, antibiotics and analgesics is essential, prior to and during loss and ablation of the epithelial layer. Granulocyte-macrophage colony-stimulating factor/granulocyte colony-stimulating factor or the use of laser light therapy may aid restitution and repair. Glutamine supplements may be beneficial in the repair/recovery phase.
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PMID:Oral and intestinal mucositis - causes and possible treatments. 1461 50

The gastrointestinal effects of intraluminal fats may be critically dependent on the chain length of fatty acids released during lipolysis. We postulated that intraduodenal administration of lauric acid (12 carbon atoms; C12) would suppress appetite, modulate antropyloroduodenal pressure waves (PWs), and stimulate the release of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) more than an identical dose of decanoic acid (10 carbon atoms; C10). Eight healthy males (19-47 yr old) were studied on three occasions in a double-blind, randomized fashion. Appetite perceptions, antropyloroduodenal PWs, and plasma CCK and GLP-1 concentrations were measured during a 90-min intraduodenal infusion of 1) C12, 2) C10, or 3) control (rate: 2 ml/min, 0.375 kcal/min for C12/C10). Energy intake at a buffet meal, immediately after completion of the infusion, was also quantified. C12, but not C10, suppressed appetite perceptions (P < 0.001) and energy intake (control: 4,604 +/- 464 kJ, C10: 4,109 +/- 588 kJ, and C12: 1,747 +/- 632 kJ; P < 0.001, C12 vs. control/C10). C12, but not C10, also induced nausea (P < 0.001). C12 stimulated basal pyloric pressures and isolated pyloric PWs and suppressed antral and duodenal PWs compared with control (P < 0.05 for all). C10 transiently stimulated isolated pyloric PWs (P = 0.001) and had no effect on antral PWs but markedly stimulated duodenal PWs (P = 0.004). C12 and C10 increased plasma CCK (P < 0.001), but the effect of C12 was substantially greater (P = 0.001); C12 stimulated GLP-1 (P < 0.05), whereas C10 did not. In conclusion, there are major differences in the effects of intraduodenal C12 and C10, administered at 0.375 kcal/min, on appetite, energy intake, antropyloroduodenal PWs, and gut hormone release in humans.
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PMID:Effects of intraduodenal fatty acids on appetite, antropyloroduodenal motility, and plasma CCK and GLP-1 in humans vary with their chain length. 1530

Options for the repair of parastomal hernias include contralateral transposition or in situ repair. The latter can be accomplished either primarily or with prosthetic mesh. Concerns with mesh include possible gut erosion and infection. Recurrence rates in the literature are dismal regardless of technique. We retrospectively reviewed our experience with this problem focusing on in situ repairs. We identified 9 patients who underwent 10 in situ repairs. Of these, 6 were women, average age was 69.4 years, and stomas had been constructed for cancer in 6, inflammatory bowel disease in 2, and incontinence in 1. Eight patients had colostomies; one had an ileostomy. All patients were symptomatic from their hernias. Repairs were performed an average of 8 years after stoma construction. Hernia repair was performed transabdominally in four and through a parastomal incision in six. Complications included hematoma formation requiring evacuation in one and delayed resumption of oral intake secondary to nausea and cramps in three. Of the 9 initial repairs, 1 recurred (11%) and was repaired without subsequent failure. No mesh erosions or wound infections have occurred. This technique is safe and may be preferable to contralateral placement of the stoma.
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PMID:In situ mesh repair of parastomal hernias. 1532 4

Nausea and vomiting are significant adverse effects of chemotherapeutic agents like cisplatin, and cause significant patient morbidity. Cisplatin treatment results in oxidant gut injury, which is postulated to be the primary cause of nausea and vomiting. We evaluated the effects of two antioxidant herbs, Scutellaria baicalensis and American ginseng berry, on cisplatin-induced nausea and vomiting using a rat model. Rats react to emetic or nausea-producing stimuli, such as cisplatin, with altered feeding habits, manifested by increased kaolin consumption (pica). We measured pica in rats to quantify cisplatin-induced nausea. We observed that pretreatment of rats with S. baicalensis or ginseng berry extracts resulted in a significant reduction in cisplatin-induced pica. The in vitro free radical scavenging ability of the herbal extract observed in the study, further confirmed the antioxidant action of the herb. We conclude that herbal antioxidants may have a role in attenuating cisplatin-induced nausea and vomiting.
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PMID:Effects of antioxidant herbs on chemotherapy-induced nausea and vomiting in a rat-pica model. 1567 95

Glucagon-like peptide-1 (GLP-1) is synthesized from proglucagon in enteroendocrine cells and regulates glucose homeostasis via multiple complementary actions on appetite, gastrointestinal motility and islet hormone secretion. GLP-1 is secreted from the distal gut in response to food ingestion, and levels of circulating GLP-1 may be diminished in patients with type 2 diabetes mellitus. GLP-1 administration stimulates glucose-dependent insulin secretion, inhibits glucagon secretion, and lowers blood glucose in normal and diabetic rodents and in humans. GLP-1 exerts additional glucose-lowering actions in patients with diabetes mellitus already treated with metformin or sulfonylurea therapy. GLP-1 inhibits gastric emptying in healthy individuals and those with diabetes mellitus, and excess GLP-1 administration may cause nausea or vomiting in susceptible individuals. Chronic GLP-1 treatment of normal or diabetic rodents is associated with bodyweight loss and GLP-1 agonists transiently inhibit food intake and may prevent bodyweight gain in humans. The potential for GLP-1 therapy to prevent deterioration of beta-cell function is exemplified by studies demonstrating that GLP-1 analogs stimulate proliferation and neogenesis of beta-cells, leading to expansion of beta-cell mass in diabetic rodents. The rapid N-terminal inactivation of bioactive GLP-1 by dipeptidyl peptidase-IV (DPP-IV) limits the utility of the native peptide for the treatment of patients with diabetes mellitus, and has fostered the development of more potent and stable protease-resistant GLP-1 analogs which exhibit longer durations of action. The importance of DPP-IV for glucose control is illustrated by the phenotype of rodents with genetic inactivation of DPP-IV which exhibit reduced glycemic excursion and increased levels of circulating GLP-1 in vivo. Inhibitors of DPP-IV potentiate incretin action by preventing degradation of GLP-1 and glucose-dependent insulinotropic peptide, and lower blood glucose in normal rodents and in experimental models of diabetes mellitus. Hence, orally available DPP-IV inhibitors also represent a new class of therapeutic agents that enhance incretin action for the treatment of patients with type 2 diabetes mellitus.
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PMID:Harnessing the therapeutic potential of glucagon-like peptide-1: a critical review. 1576 27

Glucagon-like peptide 1 (GLP-1) was discovered as an insulinotropic gut hormone, suggesting a physiological role as an incretin hormone, i.e., being responsible, in part, for the higher insulin secretory response after oral as compared to intravenous glucose administration. This difference, the incretin effect, is partially lost in patients with Type 2 diabetes. The actions of GLP-1 include (a) a stimulation of insulin secretion in a glucose-dependent manner, (b) a suppression of glucagon, (c) a reduction in appetite and food intake, (d) a deceleration of gastric emptying, (e) a stimulation of beta-cell neogenesis, growth and differentiation in animal and tissue culture experiments, and (f) an in vitro inhibition of beta-cell apoptosis induced by different toxins. Intravenous GLP-1 can normalize and subcutaneous GLP-1 can significantly lower plasma glucose in the majority of patients with Type 2 diabetes. GLP-1 itself, however, is inactivated rapidly in vivo and thus does not appear to be useful as a therapeutic agent in the long-term treatment of Type 2 diabetes. Other agents acting on GLP-1 receptors have been found (like exendin-4) or developed as GLP-1 derivatives (like liraglutide or GLP-1/CJC-1131). Clinical trials with exenatide (two injections per day) and liraglutide (one injection per day) have shown reductions in glucose concentrations and HbA1c by more than 1%, associated with moderate weight loss (2-3 kg), but also some nausea and, rarely, vomiting. It is hoped that this new class of drugs interacting with the GLP-1 or other incretin receptors, the so-called "incretin mimetics", will broaden our armamentarium of antidiabetic medications in the nearest future.
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PMID:Glucagon-like peptide 1 and its derivatives in the treatment of diabetes. 1578 Apr 33

Nutritional management during acute pancreatitis has the purpose to avoid a negative influence on the outcome and to preserve the morphofunctional integrity of the gut, preventing bacterial translocation. When the patient would start again normal nutrition after a period shorter than a week, thanks to the resolution of the clinical picture, and when the initial nutritional state of the patient is satisfactory, a particular nutritional support is not necessary. When the course of the disease is longer and the severity is higher, an early artificial nutritional support is advisable. Caloric needs thought to be useful are 25-30 kcal/kg/die; 40-60% of nutrient mixture should consist of carbohydrates and 20-30% of lipids. Proteins should be approximately 1.0-1.5 g/kg/die. On the basis of recent randomised, prospective clinical trials, enteral jejunal feeding is indicated as a first choice nutritional way, because of its ability to maintain the integrity of the intestinal barrier and its minimal effect on pancreatic secretion, acting significantly on inflammatory parameters and on prognostic markers. This procedure is not indicated when ileum is present and when it causes nausea, vomiting, abdominal pain and an increase of hepatic enzymes. In this case, parenteral feeding is an alternative. Hydroly-sated formulas, containing short peptides and a low percentage of long chain fat acids, are recommended.
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PMID:[Nutrition in acute pancreatitis]. 1578 88

This review discusses the role of dynamic medicinal chemistry in the design and development of more effective opioids for the treatment of pain. Human Phase II clinical studies have shown that morphine-6-glucuronide (M6G) has equivalent analgesic effects to morphine and an improved side effect profile particularly at reducing the tendency to cause nausea, vomiting, sedation and respiratory depression. Based on these clinical observations, a new class of pain medication could be developed. Despite the promise, M6G is not an ideal drug because bioavailability is low and hydrolysis occurs in the gut. The literature covered includes a comprehensive list of work that illustrates: (i) the role of drug metabolism and drug disposition concepts in M6G analog drug development, (ii) the use of dynamic medicinal chemistry in improving M6G pharmaceutical properties, and (iii) the role of drug metabolism in enhancing bioavailability of M6G. Using optimized dynamic medicinal chemistry procedures for drug design and development, understanding the use of drug development concepts in early drug development and applying new methods from other fields may help advance this field of drug development. This review summarizes studies that support the feasibility of elaborating longer-acting, less expensive pain medications with possibly a safer profile of side effects. Development of new pain medications for cancer and other diseases based on M6G could provide novel agents that could balance optimal analgesia with a decreased occurrence of adverse side effects.
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PMID:Dynamic medicinal chemistry in the elaboration of morphine-6-glucuronide analogs. 1602 81

Taste aversion learning (TAL) consists of the avoidance of a taste previously associated with a noxious visceral stimulus. Clinical and experimental studies suggest that this adaptive process can be established by different procedures that imply distinct forms of learning and memory, although the final result is analogous, i.e. avoidance of the gustatory stimulus associated with gastrointestinal discomfort. In fact, a double neurobiological system has been anatomically dissociated and, functionally, may be implicated in nausea and emesis, in food selection, and in neuroimmune interactions. Actually, a dual, parallel, and non-redundant gut-brain system has been proposed that sustain two different TAL modalities, concurrent and sequential. Concurrent TAL requires several trials and is inflexible, requiring simultaneity of the stimuli and the participation of the vagus nerve. In contrast, sequential TAL can be acquired in one trial and is flexible, permits long inter-stimulus delays, and is independent of vagal pathways. These two TAL modalities are analyzed in the light of the recent proposal that different acquisition processes are sustained by distinct cerebral systems.
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PMID:Concurrent conditioned taste aversion: a learning mechanism based on rapid neural versus flexible humoral processing of visceral noxious substances. 1608 90

Enterally administered lipid modulates antropyloroduodenal motility, gut hormone release, appetite, and energy intake. We hypothesized that these effects would be dependent on both the load, and duration, of small intestinal exposure to lipid. Eleven healthy men were studied on four occasions in a double-blind, randomized, fashion. Antropyloroduodenal motility, plasma CCK and peptide YY (PYY) concentrations, and appetite perceptions were measured during intraduodenal infusion of lipid (Intralipid) at 1) 1.33 kcal/min for 50 min, 2) 4 kcal/min for 50 min, and 3) 1.33 kcal/min for 150 min, or 4) saline for 150 min. Immediately after the infusions, energy intake was quantified. Pressure wave sequences (PWSs) were suppressed, and basal pyloric pressure, isolated pyloric pressure waves (IPPWs), plasma CCK and PYY stimulated (all P < 0.05), during the first 50 min of lipid infusion, in a load-dependent fashion. The effect of the 4 kcal/min infusion was sustained so that the suppression of antral pressure waves (PWs) and PWSs and increase in PYY remained evident after cessation of the infusion (all P < 0.05). The prolonged lipid infusion (1.33 kcal/min for 150 min) suppressed antral PWs, stimulated CCK and PYY and basal pyloric pressure (all P < 0.05), and tended to stimulate IPPWs when compared with saline throughout the entire infusion period. There was no significant effect of any of the lipid infusions on appetite or energy intake, although nausea was slightly higher (P < 0.05) with the 4 kcal/min infusion. In conclusion, both the load, and duration, of small intestinal lipid influence antropyloroduodenal motility and patterns of CCK and PYY release.
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PMID:Effects of load, and duration, of duodenal lipid on antropyloroduodenal motility, plasma CCK and PYY, and energy intake in healthy men. 1621 Apr 15


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