Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From June 1988 to November 1990 the Southwest Oncology Group initiated nine protocols for the phase II evaluation of recombinant human tumor necrosis factor alpha (rhuTNF alpha) in cancer patients. Patients with diverse metastatic malignancies including breast, colon, gastric, pancreatic, endometrial, and bladder cancers, as well as multiple myeloma and various sarcomas received 150 micrograms/m2 of rhuTNF alpha daily for 5 days every other week. Of 147 patients entered in the study, 127 were eligible and were evaluated for toxicity and response. Of 124 patients known to have completed treatment, 92 (74%) went off study for progression, 21 (17%) for toxicity, and 12 (10%) for other causes, mainly that of worsening medical condition. Thirteen percent of patients experienced grade 4 or fatal toxicity. The most serious toxicities were pulmonary failure and coagulopathies. The predominant grade 3 toxicities were symptomatic (chills, fever, malaise, headache, myalgia, and nausea or vomiting). Only one partial remission was seen in a patient with metastatic bladder cancer lasting 4 months (rate 0.8%, exact 95% confidence interval 0-4%). At the study dose and schedule, rhuTNF alpha does not appear to have significant antitumor activity. The biological basis for this finding is discussed.
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PMID:Phase II studies of recombinant human tumor necrosis factor alpha in patients with malignant disease: a summary of the Southwest Oncology Group experience. 176 76

Endotoxemia occurs when intestinal ischemia allows bacterial lipopolysaccharide to translocate from colonic flora into the bloodstream, which triggers release of cytokines that can cause hypotension, rigors, fever, shock, and even death. Recently, blood endotoxin levels were shown to be higher in athletes needing medical attention (330 pg.ml-1) than in their competitors with similar performances (81 pg.ml-1). Though there were no data showing that these athletes had elevated core temperatures or severe illness, speculation followed that endotoxin may play a causal role in heat stroke. We examined the relationship between endotoxemia and mild post-exertional illness in 39 cyclists after a 100-mile ride. Thirteen cyclists had at least one of the following: orthostatic hypotension, rigors, nausea, vomiting, diarrhea, or syncope. Only 2/26 case-controls had any of these symptoms. Data were collected on vital signs, hemoglobin, sodium, creatine kinase, creatinine, and uric acid. Endotoxin titer was determined by chromogenic assay; tumor necrosis factor alpha (TNF-alpha) titer was determined by ELISA. One ill cyclist had an endotoxin level of 330 pg.ml-1, one control had an endotoxin level of 150 pg.ml-1, but endotoxin level was < or = 64 pg.ml-1 in all others. Comparison of pre- and post-ride data showed that controls increased creatine kinase activity (154 +/- 34 vs 561 +/- 191 IU.dl, P < 0.05), creatinine concentration (1.5 +/- 0.0 vs 1.6 +/- 0.0 mg.dl-1, P < 0.05), and uric acid concentration (5.4 +/- 0.3 vs 6.3 +/- 0.3 mg.dl-1, P < 0.05). Ill cyclists had lower serum sodium than post-ride controls (138 +/- 2 vs 142 +/- 0.6 mEq.l-1, P < 0.05), but there were no differences between groups in CK, creatinine, or uric acid. These findings suggest that endotoxemia may complicate, but does not cause mild post-exertional illness in cyclists.
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PMID:Exercise-associated collapse in cyclists is unrelated to endotoxemia. 853 21

Pentoxifylline, a methylxanthine derivative and nonspecific type 4 phosphodiesterase inhibitor, has been used to improve survival of animals with sepsis and to attenuate lung injury in acute lung inflammation. The purpose of this study was to examine whether pentoxifylline would inhibit the expression of inflammatory cytokines, particularly tumor necrosis factor alpha (TNF), and thereby decrease the pathophysiology of acute porcine pleuropneumonia. E. coli lipopolysaccharide (LPS) and bacterial extracts of A. pleuropneumoniae--induced elevations in TNF mRNA which were fully abrogated by addition of pentoxifylline in both alveolar macrophage and neutrophil cultures. A 30% reduction in the level of LPS-induced interleukin (IL)-1beta mRNA levels also was achieved in macrophages. Pentoxifylline did not affect either IL-1alpha or IL-8 expression in vitro. Pentoxifylline therapy in vivo significantly reduced the number of band neutrophils in swine but did not reduce the pathology associated with pleuropneumonia, including changes in serum zinc, iron, or haptoglobin. Neither did it alter TNF, IL-1, IL-6, or IL-8 expression. Measurement of pentoxifylline and its metabolites in pig sera suggested that efficacious doses of pentoxifylline were probably not achieved in vivo. However, subcutaneous doses of pentoxifylline higher than 25 mg/kg produced transient diarrhea, vomiting, and tremors. These results suggest that pentoxifylline is an effective pharmacological tool for the dissection of cytokine regulation in vitro, but inhibitory concentrations may not be achievable for in vivo pharmacological use in swine.
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PMID:Effects of pentoxifylline on inflammatory cytokine expression and acute pleuropneumonia in swine. 1199 42

The cytokine tumor necrosis factor alpha (TNF(alpha)) may act within the neural circuitry of the medullary dorsal vagal complex (DVC) to affect changes in gastric function such as gastric stasis, loss of appetite, nausea, and vomiting. The definitive demonstration that endogenously generated TNF(alpha) is acting within the DVC circuitry to affect these changes has been impeded by the lack of an antagonist for TNF(alpha). The present studies used localized central nervous system microinjections of the TNF-adsorbant construct (TNFR:Fc) to specifically neutralize the ability of endogenously produced TNF(alpha) to activate NST neurons. Our studies reveal that TNFR:Fc suppresses induction of cFos normally evoked by TNF(alpha). These results validate our hypothesis that circulating TNF(alpha) may act directly within the DVC to affect gastric function in a variety of pathophysiological states.
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PMID:TNFalpha-stimulation of cFos-activation of neurons in the solitary nucleus is suppressed by TNFR:Fc adsorbant construct in the dorsal vagal complex. 1276 23

Chemotherapy is 1 method for the treatment of cancer, but serious side effects can sometimes limit the dosage given. Mild fever and diarrhea are common side effects of cancer chemotherapy. Gastrointestinal injury induced by chemotherapeutic agents may result in bacterial/endotoxin translocation from the gut into the systemic circulation. An experimental study was therefore conducted to clarify the effect of systemic chemotherapeutic agents on gastrointestinal barrier function. Male Wistar rats were divided into a 5-fluorouracil (5-FU) group (100 mg/kg/day for 4 days; n = 27) and a control group (n = 5). All rats were fasted and central venous catheterization was performed for total parenteral nutrition and blood sampling. Intestinal tissue was also sampled for pathological examination. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha) were determined by ELISA, bacterial translocation was quantified by lymph node culture and plasma endotoxin content of portal blood was measured by the Limulus-amebocyte-lysate test. In the 5-FU group on day 4, a proportion of rats exhibited severe watery diarrhea (73.9%) and occasional vomiting (86.2%). The levels of plasma TNFalpha and IL-6 were seen to increase, peaking at day 6 (IL-6, 350.0 +/- 67.8 pg/ml; TNFalpha, 26.1 +/- 3.2 pg/ml). The pathological findings also changed on day 4. On day 6, 90% of the rats in the 5-FU group showed dramatic sepsis-like manifestations, whereas the control group did not. Within the 5-FU group, only at day 6 was bacterial translocation in the rat mesenteric lymph nodes or significantly elevated levels of endotoxin evident. These results suggest that bacterial/endotoxin translocation might cause sepsis-like manifestations after systemic chemotherapy.
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PMID:Simultaneous onset of acute inflammatory response, sepsis-like symptoms and intestinal mucosal injury after cancer chemotherapy. 1294 12

Rotavirus is the most common cause of severe gastroenteritis in young children, but the pathogenesis and immunity of this disease are not completely understood. To examine the host response to acute infection, we collected paired serum specimens from 30 children with rotavirus diarrhea and measured the levels of nine cytokines (interleukin-1beta [IL-1beta], IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, gamma interferon [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]) using a microsphere-based Luminex Flowmetrix system. Patients with acute rotavirus infection had elevated median levels of seven cytokines in serum, and of these, the levels of three (IL-6, IL-10, and IFN-gamma) were significantly (P < 0.05) higher than those in serum from control children without diarrhea. Patients with fever had significantly (P < 0.05) higher levels of IL-6 in serum than control children, and those with fever and more episodes of diarrhea had significantly (P < 0.05) higher levels of TNF-alpha than those without fever and with fewer episodes of diarrhea. We further demonstrated a negative association (P < 0.05) between the levels of IL-2 and the number of stools on the day on which the first blood sample was collected. Finally, patients with vomiting had significantly (P < 0.05) lower levels of IFN-gamma than those without vomiting. Our pilot study provides evidence that the types and magnitudes of cytokine responses to rotavirus infection in children influence or reflect the clinical outcome of disease. These findings suggest that certain cytokines may play an important role in the pathogenesis of and the protection against rotavirus disease in children and, consequently, may provide directions and insights that could prove critical to the prevention or treatment of this important disease.
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PMID:Cytokines as mediators for or effectors against rotavirus disease in children. 1460 58

Cannabinoids, the active components of marijuana and their endogenous counterparts were reported as useful analgetic agents to accompany primary cancer treatment by preventing nausea, vomiting, and pain and by stimulating appetite. Moreover, they have been shown to inhibit cell growth and to induce apoptosis in tumor cells. Here, we demonstrate that anandamide, Delta(9)-tetrahydrocannabinol (THC), HU-210, and Win55,212-2 promote mitogenic kinase signaling in cancer cells. Treatment of the glioblastoma cell line U373-MG and the lung carcinoma cell line NCI-H292 with nanomolar concentrations of THC led to accelerated cell proliferation that was completely dependent on metalloprotease and epidermal growth factor receptor (EGFR) activity. EGFR signal transactivation was identified as the mechanistic link between cannabinoid receptors and the activation of the mitogen-activated protein kinases extracellular signal-regulated kinase 1/2 as well as prosurvival protein kinase B (Akt/PKB) signaling. Depending on the cellular context, signal cross-communication was mediated by shedding of proAmphiregulin (proAR) and/or proHeparin-binding epidermal growth factor-like growth factor (proHB-EGF) by tumor necrosis factor alpha converting enzyme (TACE/ADAM17). Taken together, our data show that concentrations of THC comparable with those detected in the serum of patients after THC administration accelerate proliferation of cancer cells instead of apoptosis and thereby contribute to cancer progression in patients.
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PMID:Cannabinoids induce cancer cell proliferation via tumor necrosis factor alpha-converting enzyme (TACE/ADAM17)-mediated transactivation of the epidermal growth factor receptor. 1502 28

During disease, infection, or trauma, the cytokine tumor necrosis factor alpha (TNF alpha) causes fever, fatigue, malaise, allodynia, anorexia, gastric stasis associated with nausea, and emesis via interactions with the central nervous system. Our studies have focused on how TNF alpha produces a profound gastric stasis by acting on vago-vagal reflex circuits in the brainstem. Sensory elements of this circuit (i.e., nucleus of the solitary tract [NST] and area postrema) are activated by TNF alpha. In response, the efferent elements (i.e., dorsal motor neurons of the vagus) cause gastroinhibition via their action on the gastric enteric plexus. We find that TNF alpha presynaptically modulates the release of glutamate from primary vagal afferents to the NST and can amplify vagal afferent responsiveness by sensitizing presynaptic intracellular calcium-release mechanisms. The constitutive presence of TNF alpha receptors on these afferents and their ability to amplify afferent signals may explain how TNF alpha can completely disrupt autonomic control of the gut.
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PMID:TNFalpha: a trigger of autonomic dysfunction. 1791 Dec 24

Hepatopulmonary syndrome (HPS) results when chronic liver disease or portal hypertension causes intrapulmonary microvascular dilatation with hypoxemia. In experimental HPS, tumor necrosis factor alpha (TNF-alpha) overproduction contributes to vasodilatation, which is improved by pentoxifylline, a TNF-alpha inhibitor. The effectiveness of pentoxifylline in humans is unknown. The aim of this open-label, single-arm clinical trial was to assess the efficacy and tolerability of pentoxifylline in patients with cirrhosis and advanced HPS undergoing liver transplantation evaluation. Nine adults with cirrhosis and moderate to severe HPS were enrolled. All patients had an initial 2-week titration to a target dose of pentoxifylline of 400 mg by mouth every 8 hours, which was continued for 6 weeks. Baseline and follow-up arterial blood gases and TNF-alpha levels were evaluated. Adverse effects and tolerability were assessed. The 9 patients had a mean age of 55 +/- 10 years, and 67% were female. The most common causes of cirrhosis were hepatitis C virus and alcohol (55%). The mean Model for End-Stage Liver Disease score was 11 (range, 6-19), and patients had advanced hypoxemia [mean partial pressure of arterial oxygen (PaO(2)) = 54 +/- 12 mm Hg, mean alveolar-arterial oxygen gradient (A-a PaO(2)) = 57 +/- 15 mm Hg]. Of the 9 patients enrolled, follow-up blood gases were done in 7. There was no significant change in PaO(2) (P = 0.3) or A-a PaO(2) (P = 0.3) with treatment. Pentoxifylline was poorly tolerated. Nausea (100%) and vomiting (56%) were the predominant side effects, and only a single patient was able to complete full-dose therapy. Treatment with pentoxifylline did not improve arterial oxygenation in advanced HPS, and tolerance was limited by gastrointestinal toxicity.
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PMID:Pilot study of pentoxifylline in hepatopulmonary syndrome. 1866 53

We investigated associations between markers of damage of vascular endothelial cells (MDVECs) and plasma cytokine levels, hemoglobin level and temperature in individuals with acute uncomplicated malaria, as well as healthy controls, using enzyme linked immunosorbent assay (ELISA) for the presence of soluble endothelial cell adhesion molecule-1 (sE-selectin), circulating granule membrane protein-140 (sP-selectin), circulating thrombomodulin (TM), circulating von Willebrand factor (VWf), interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha). Significant differences were observed between falciparum malaria patients and the healthy people in term of levels of both sE-selectin and TM. The serum levels of sP-selectin and VWf were comparable between the two groups. The levels of both sE-Selectin and TM correlated positively with temperature, levels of IFN-gamma and levels of TNF-alpha; and negatively with hemoglobin levels. Trends of positive correlations were observed between level of sP-selectin or VWf and temperature. Furthermore, sE-selectin levels correlated with vomiting. These data suggest that sE-selectin and TM might be useful markers of endothelium activation in in vivo studies. Moreover, our results highlight the use of both sE-selctin and TM as markers of anemia.
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PMID:Markers of vascular endothelial cell damage and P. falciparum malaria: association between levels of both sE-selectin and thrombomodulin, and cytokines, hemoglobin and clinical presentation. 1877 3


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