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)

Mirtazapine and olanzapine are easy-to-use psychiatric drugs with potent antinausea effects. Ondansetron and later members of the 'setron class are currently standard treatments for cancer chemotherapy-related nausea and emesis. They are potent 5-HT3 blockers, but it is often not appreciated that mirtazapine and olanzapine bind with similar affinity to 5-HT3 receptors, have a longer half-life, are considerably cheaper than the 'setron class, and often offer better and smoother 24-h nausea control than 'setron class drugs. Mirtazapine and olanzapine often have salutary antianxiety effects and improve sleep quality. They occasionally relieve chemotherapy-related and advanced cancer-related nausea and appetite decrease better than the 'setron group that are specifically marketed for nausea control. Mirtazapine and olanzapine frequently give potent nausea reduction and appetite increase in advanced cancer-related cachexia. Several cytokine changes potentially induced by mirtazapine and olanzapine use are discussed that may have salutary effects in several cancers. We suggest mirtazapine and olanzapine be included as first-line options in treating both chemotherapy- and advanced cancer-related nausea. Multiple clinical and economic advantages of mirtazapine and olanzapine over currently used 'setron class medicines are reviewed. Double-blind studies against the 'setron class drugs are warranted.
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PMID:Cancer chemotherapy and cachexia: mirtazapine and olanzapine are 5-HT3 antagonists with good antinausea effects. 1758 60

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

Serial changes in the circulating and cerebrospinal fluid (CSF) cytokine levels were assessed in a patient with Sjogren's syndrome (SS)-associated meningoencephalomyelitis. A 16-yr-old girl diagnosed as having primary SS at 8 yr of age presented headache and vomiting. CSF studies revealed lymphocyte-dominant pleocytosis and high IgM index, but no evidence of infection. Disturbed consciousness and diffuse slow waves on electroencephalogram led to the diagnosis of SS-meningoencephalitis. The clinical condition subsided after a cycle of dexamethasone therapy, however, 2 months later urinary retention and paresthesia of the lower body developed. Craniospinal magnetic resonance imaging (MRI) showed extensive intraparenchymal lesions with high T2-weighted signal intensity adjacent to the posterior left horn of lateral ventricle of the brain and the longitudinal lesion from C5 to T10 of the spinal cord. High-dose methyl-prednisolone and subsequent tacrolimus therapy has effectively controlled the activity of SS-meningoencephalomyelitis. Monitoring of systemic and CSF cytokine levels during the course of illness revealed that CSF interleukin-6, but not interferon-gamma or tumor necrosis factor-alpha levels were the sensitive indicator of disease activity. The unique cytokine profile, differing from those of infectious meningitis may be useful for predicting the central nervous system involvement in autoimmune disease.
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PMID:Sjogren's syndrome-associated meningoencephalomyelitis: cerebrospinal fluid cytokine levels and therapeutic utility of tacrolimus. 1799 6

The structure-activity relationship of a novel series of 8-biarylquinolines acting as type 4 phosphodiesterase (PDE4) inhibitors is described herein. Prototypical compounds from this series are potent and non-selective inhibitors of the four distinct PDE4 (IC(50)<10 nM) isozymes (A-D). In a human whole blood in vitro assay, they inhibit (IC(50)<0.5 microM) the LPS-induced release of the cytokine TNF-alpha. Optimized inhibitors were evaluated in vivo for efficacy in an ovalbumin-induced bronchoconstriction model in conscious guinea pigs. Their propensity to produce an emetic response was evaluated by performing pharmacokinetic studies in squirrel monkeys. This work has led to the identification of several compounds with excellent in vitro and in vivo profiles, including a good therapeutic window of efficacy over emesis.
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PMID:Design, synthesis, and biological evaluation of 8-biarylquinolines: a novel class of PDE4 inhibitors. 1820 97

Necrotizing enterocolitis (NEC) is primarily a disease process of the gastrointestinal (GI) tract of premature neonates that results in inflammation and bacterial invasion of the bowel wall. Despite advances in the care of premature infants, NEC remains one of the leading causes of morbidity and mortality in this population. It occurs in 1-5% of all neonatal intensive care admissions and 5-10% of all very low birthweight (<1500 g) infants. Although research has presented an interesting array of potential contributing factors, the precise aetiology of this multifactorial disease process remains elusive. Historically, it was believed that NEC arose predominantly from ischaemic injury to the immature GI tract, yet alternate plausible hypotheses indicate that many factors are likely to be involved. These may include issues related to the introduction and advancement of enteric feeding, alterations in the normal bacterial colonization of the GI tract, bacterial translocation and activation of the cytokine cascade, decreased epidermal growth factor, increased platelet activating factor, and mucosal damage from free radical production. Clinical manifestations of NEC may be vague, including increased episodes of apnoea, desaturations, bradycardia, lethargy and temperature instability. There may also be GI-specific symptoms such as feeding intolerance, emesis, bloody stools, abdominal distention and tenderness, and abdominal wall discolouration. Laboratory values may be indicative of infection, coagulation abnormalities and fluid retention. Radiographic signs may include ileus, dilated or fixed intestinal loops, air in the intestinal wall or free air in the abdomen. Medical treatment typically consists of bowel rest and decompression, antibacterial therapy, and management of other haematological or electrolyte imbalances. Increased respiratory and cardiovascular support is sometimes needed. In neonates who do not respond adequately to medical management, or if pneumoperitoneum is present, surgical intervention may occur with either use of a peritoneal drain or laparotomy. Advances in antenatal and neonatal care have resulted in increased survival of extremely preterm neonates. As this at-risk population continues to increase, an effective preventative strategy for NEC is needed. One preventative strategy is the use of antenatal corticosteroids to enhance maturation of the fetus if preterm delivery is likely. Recommendation of use of breast milk, early initiation of trophic feeds and judicoius advancement of enteric feeds are current postnatal strategies. Other preventative strategies that have been investigated include the use of oral antibacterials, antioxidants, supplementation of arginine and epidermal growth factor, none of which have changed clinical practice. Recent promising data indicate that prophylactic use of probiotics may play a role in preventing the onset of NEC. However, more large-scale, definitive studies are needed.
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PMID:Necrotizing enterocolitis in newborns: pathogenesis, prevention and management. 1854 33

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

Opiates, such as morphine, are typically employed to alleviate acute or chronic pain states. However, there are a myriad of side effects including constipation, nausea, respiratory depression, cough suppression, vomiting, sedation, addiction and tolerance. It has also been reported experimentally and clinically that exposure to opiate can elicit paradoxical pain (opiate-induced tactile hyperalgesia; OIH) in regions of the body unrelated to the initial pain complaint. Several mechanisms have been suggested to be responsible for OIH such as sensitization of peripheral nociceptors, enhanced production/release of glutamate and neuropeptides in the spinal cord, protein kinase C gamma-induced signaling, and/or enhanced descending facilitation of nociceptive pathways from the rostral ventromedial medulla; however signaling pathways known to lead to directly to OIH remain undiscovered. Recent publications from our laboratory and others have discovered a potentially important link to OIH that involves the chemokine (chemotactic cytokine), stromal-derived factor 1 (SDF1 also known as CXCL12) and its cognate receptor CXCR4.
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PMID:Opiate-induced hypernociception and chemokine receptors. 1960 47

Amphotericin B (AmB) is a crucial agent in the management of serious systemic fungal infections. In spite of its proven track record, its well-known side effects and toxicity will sometimes require discontinuation of therapy despite a life-threatening systemic fungal infection. The mechanism of action of AmB is based on the binding of the AmB molecule to the fungal cell membrane ergosterol, producing an aggregate that creates a transmembrane channel, allowing the cytoplasmic contents to leak out, leading to cell death. Most of the efforts at improving AmB have been focused on the preparation of AmB with a lipid conjugate. AmB administration is limited by infusion-related toxicity, an effect postulated to result from proinflammatory cytokine production. The principal acute toxicity of AmB deoxycholate includes nausea, vomiting, rigors, fever, hypertension or hypotension, and hypoxia. Its principal chronic adverse effect is nephrotoxicity. AmB probably produces renal injury by a variety of mechanisms. Risk factors for AmB nephrotoxicity include male gender, higher average daily dose of AmB (> or = 35 mg/day), diuretic use, body weight > or = 90 kg, concomitant use of nephrotoxic drugs, and abnormal baseline renal function. Clinical manifestations of AmB nephrotoxicity include renal insufficiency, hypokalemia, hypomagnesemia, metabolic academia, and polyuria due to nephrogenic diabetes insipidus. Human studies show convincingly that sodium loading in excess of the usual dietary intake notably reduces the incidence and severity of AmB-induced nephrotoxicity.
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PMID:Amphotericin B: side effects and toxicity. 1983 85

We report a 4-year-old boy with fulminating meningitis caused by Haemophilus influenzae (Hib). He suddenly developed fever, vomiting and then somnolence. As bacterial meningitis was suspected, treatment with antibiotics was started at 12 hours after the onset. However, there was a rapid progression of severe brain edema and brain hernia, leading to clinical brain death. His clinical course and neuroradiological findings mimicked those in patients with acute encephalopathy, with cytokine profiles in cerebrospinal fluid demonstrating a marked increase of inflammatory cytokines. From a review of the literature, fulminating Hib meningitis may be classified into two disease types: DIC plus multiple organ failure and acute brain swelling types. The present case belongs to the latter type, in which cytokine storm seems to play an important pathogenic role.
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PMID:[Fulminating meningitis caused by Haemophilus influenzae with rapid progression of severe brain edema similar to acute encephalopathy]. 1992 44

PURPOSE Pazopanib is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit. This randomized, double-blind, placebo-controlled phase III study evaluated efficacy and safety of pazopanib monotherapy in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS Adult patients with measurable, locally advanced, and/or metastatic RCC were randomly assigned 2:1 to receive oral pazopanib or placebo. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, tumor response rate (Response Evaluation Criteria in Solid Tumors), and safety. Radiographic assessments of tumors were independently reviewed. Results Of 435 patients enrolled, 233 were treatment naive (54%) and 202 were cytokine pretreated (46%). PFS was significantly prolonged with pazopanib compared with placebo in the overall study population (median, PFS 9.2 v 4.2 months; hazard ratio [HR], 0.46; 95% CI, 0.34 to 0.62; P < .0001), the treatment-naive subpopulation (median PFS 11.1 v 2.8 months; HR, 0.40; 95% CI, 0.27 to 0.60; P < .0001), and the cytokine-pretreated subpopulation (median PFS, 7.4 v 4.2 months; HR, 0.54; 95% CI, 0.35 to 0.84; P < .001). The objective response rate was 30% with pazopanib compared with 3% with placebo (P < .001). The median duration of response was longer than 1 year. The most common adverse events were diarrhea, hypertension, hair color changes, nausea, anorexia, and vomiting. There was no evidence of clinically important differences in quality of life for pazopanib versus placebo. CONCLUSION Pazopanib demonstrated significant improvement in PFS and tumor response compared with placebo in treatment-naive and cytokine-pretreated patients with advanced and/or metastatic RCC.
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PMID:Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. 2081 65


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