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)

The majority of human malignancies have aberrancies in the Retinoblastoma (Rb) pathway. Loss in Rb function results from the phosphorylation and inactivation of Rb by the cyclin-dependent kinases (cdks), main regulators of cell cycle progression. Thus, modulators of cdks may have a role in the treatment of human malignancies. Flavopiridol, the first cdk modulator tested in clinical trials, demonstrates interesting preclinical features: cell cycle block, induction of apoptosis, promotion of differentiation, inhibition of angiogenic processes and modulation of transcriptional events. Initial clinical trials with infusional flavopiridol demonstrated activity in some patients with lymphomas and renal, colon gastric carcinomas. Main side effects were diarrhea and hypotension. Phase 2 trials with infusional flavopiridol, other schedules and combination with standard chemotherapies are ongoing. The second cdk modulator tested in clinical trials, UCN-01, is a PKC inhibitor that can also modulate cdk activity. Similar to flavopiridol, UCN-01 blocks cell cycle progression and promotes apoptosis. Moreover, UCN-01 may abrogate checkpoints induced by genotoxic stress due to inhibition of chk1 kinase. The first clinical trial of UCN-01 demonstrated very prolonged half-life (approximately 600 h), due to high binding affinity of UCN-01 to the human alpha-1-acid glycoprotein. Main side effects were headaches, vomiting, hypoxemia and hyperglycemia. Clinical activity was observed in some patients with melanoma and lymphoma. Trials of shorter infusions of UCN-01 or in combination with standard chemotherapeutic agents are ongoing. Although several important basic and clinical questions remain unanswered, development of cdk modulators is a reasonable strategy for cancer therapy.
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PMID:Small molecule modulators of cyclin-dependent kinases for cancer therapy. 1142 45

14 cattle (mainly younger ones) of a total of 50 extensively kept Galloways died within 6 weeks in late winter 2001/02. According to the owner's report, grass growth had been rather poor; therefore, the herd was fed additionally hay as well as large amounts of tulip onions. In the microbiological examination a highly reduced hygienic quality of the roughage could be detected. In the rumen contents of two dissected young cattle parts of tulip onions were found. According to pertinent literature, tulip onions (in particular their external layers) contain variant-specific amounts of anti-nutritive substances; main active agents are tulipin (a glycoprotein), tuliposid A and B, and lectins. They may cause intensive mucosal irritation, accompanied by reduced feed digestion and body-weight gains, drooling, vomiting and diarrhea. This case report underlines risks caused by feeding of plants originally not destined as forage, if their active ingredients and effects are unknown or remain unconsidered.
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PMID:[Animal nutrition for veterinarians--actual cases: tulip bulbs with leaves (Tulipa gesneriana)--an unusual and high risk plant for ruminant feeding]. 1291 Aug 70

Human chorionic gonadotropin (hCG) is a glycoprotein hormone that has structural similarity to TSH. At the time of the peak hCG levels in normal pregnancy, serum TSH levels fall and bear a mirror image to the hCG peak. This reduction in TSH suggests that hCG causes an increased secretion of T4 and T3. Women with hyperemisis gravidarum often have high hCG levels that cause transient hyperthyroidsm. In the vast majority of such patients, there will be spontaneous remission of the increased thyroid function when the vomiting stops in several weeks. When there are clinical features of hyperthyroidism, it is be reasonable to treat with antithyroid drugs or a beta-adrenergic blocker, but treatment is rarely required beyond 22 weeks of gestation. Hyperthyroidism or increased thyroid function has been reported in many patients with trophoblastic tumors, either hydatiditform mole or choriocarcinoma. The diagnosis of hydatidiform mole is made by ultrasonography that shows a 'snowstorm' appearance without a fetus. Hydatidiform moles secrete large amounts of hCG proportional to the mass of the tumor. The development of hyperthyroidism requires hCG levels of >200 U/ml that are sustained for several weeks. Removal of the mole cures the hyperthyroidism. There have been many case reports of hyperthyroidism in women with choriocarcinoma and high hCG levels. The principal therapy is chemotherapy, usually given at a specialized center. With effective chemotherapy, long-term survival exceeds 95%. A unique family with recurrent gestational hyperthyroidism associated with hyperemesis gravidarum was found to have a mutation in the extracellular domain of the TSH receptor that made it responsive to normal levels of hCG.
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PMID:Physiological and pathological aspects of the effect of human chorionic gonadotropin on the thyroid. 1515 39

We report an unusual case with macro-amylasemia with coexistent selective IgA deficiency and antiphospholipid antibodies. A 16-year-old girl was referred to us with a history of episodic abdominal pain accompanied by vomiting and diarrhea. Macroamylasemia was demonstrated by precipitation of 99% amylase activity with polyethylene glycol 6000. She had high levels of anticardiolipin IgG and beta2 glycoprotein 1 IgG antibodies in the blood, but no evidence of clinical criteria of antiphospholipid syndrome. In the literature, although macro-amylasemia has been found to occur in a variety of diseases including autoimmune disorders, to our knowledge, this is the first well-documented case of macro-amylasemia associated with selective IgA deficiency and the presence of antiphospholipid antibodies. It is important that clinicians be aware of their existence in order to avoid unnecessary procedures and that the patient is informed of the macro-amylasemia; moreover, it should be stated in the patient's health record.
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PMID:Macro-amylasemia in a patient with selective IgA deficiency and antiphospholipid antibodies. 1683 Mar 1

Coronary thrombosis is a pivotal event in the pathogenesis of acute coronary syndromes and ischemic complications resulting from coronary intervention. Activation of the platelet glycoprotein (GP) IIb/IIIa receptor is the final common pathway leading to platelet aggregation, coronary thrombus formation, and myocardial ischemia. Inhibitors of platelet GP IIb/IIIa are potent agents to prevent progression to myocardial infarction and death. We prospectively surveyed the indications, frequency, and complications associated with the use of GP IIb/IIIa inhibitors in percutaneous coronary intervention in a tertiary center setting. A total of 170 patients underwent screening over a period of 6 weeks. One hundred four (61%) had coronary intervention, out of which eight (8%) had failed intervention. Glycoprotein IIb/IIIa inhibitors were used in 57 (55%) patients; 47 (45%) did not have any agent periprocedure. Eptifibatide was the most commonly used agent in 35 (33%), followed by abciximab in 19 (18%) and tirofiban in 3 (3%). Out of 57 patients in whom GP IIb/IIIa agents were used, 22 (38%) had visible intracoronary thrombus, 22 (38%) had diffuse disease, 8 (14%) had complex intervention, and 5 (9%) had diabetes. The overall incidence of complications was not increased by the use of GP IIb/IIIa inhibitors; serious complications were rare with the use of GP IIb/IIIa agents; no stroke, thrombocytopenia, gastrointestinal bleed, or death was recorded. The overall use in emergency settings was not associated with increased complications. Bradycardia and vomiting were more common with abciximab group, whereas puncture site pain was commoner in eptifibatide group.
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PMID:An audit of the use and complications of glycoprotein IIb/IIIa inhibitors in percutaneous coronary intervention against national UK standards. 1717 71

The aim of this study was to determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of bortezomib plus docetaxel in patients with anthracycline-pretreated advanced/metastatic breast cancer. Forty-eight patients received up to eight 21-day cycles of docetaxel (60-100 mg m(-2) on day 1) plus bortezomib (1.0-1.5 mg m(-2) on days 1, 4, 8, and 11). Pharmacodynamic and pharmacokinetic analyses were performed in a subset of patients. Five patients experienced DLTs: grade 3 bone pain (n=1) and febrile neutropenia (n=4). The MTD was bortezomib 1.5 mg m(-2) plus docetaxel 75 mg m(-2). All 48 patients were assessable for safety and efficacy. The most common adverse events were diarrhoea, nausea, alopecia, asthenia, and vomiting. The most common grade 3/4 toxicities were neutropenia (44%), and febrile neutropenia and diarrhoea (each 19%). Overall patient response rate was 29%. Median time to progression was 5.4 months. In patients with confirmed response, median time to response was 1.3 months and median duration of response was 3.2 months. At the MTD, response rate was 38%. Pharmacokinetic characteristics of bortezomib/docetaxel were comparable with single-agent data. Addition of docetaxel appeared not to affect bortezomib inhibition of 20S proteasome activity. Mean alpha-1 acid glycoprotein concentrations increased from baseline at nearly all time points across different bortezomib dose levels. Bortezomib plus docetaxel is an active combination for anthracycline-pretreated advanced/metastatic breast cancer. The safety profile is manageable and consistent with the side effects of the individual agents.
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PMID:Bortezomib/docetaxel combination therapy in patients with anthracycline-pretreated advanced/metastatic breast cancer: a phase I/II dose-escalation study. 1845 59

Chikungunya virus is a mosquito-transmitted RNA virus and emerging as a pathogen that has a major public health impact because of the high morbidity including high fever, headache, rash, nausea, vomiting, myalgia, arthralgia with or without neurological manifestation or fulminant hepatitis. One hundred fifty-one patient samples were analyzed during the years 2006-2008, and compared conventional tests and CCRT-PCR (cell culture RT PCR). The conventional tests included ELISA, inoculation into C6/36 cell line and CPE were examined by PCR after RNA extraction. A total of 20/151 (13.2%), 8/151 (5.29%) and 7/151 (4.6%) samples were found to be positive by ELISA, cell culture and PCR, respectively. While 7/20 (35%) of the samples were positive by CCRT_PCR when ELISA 20 positive samples were detected. A total of 5/7 positive strains were sequenced in the E1 gene region. Remarkable changes (M269V, D284E, P294L, S295F, A316V, V322A, and C328W) were observed in the membrane fusion glycoprotein E1. These unique molecular features of the isolates with the continuing epidemic demonstrated high evolutionary potential and thereby indicating higher virulence.
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PMID:Molecular epidemiology of Chikungunya virus: mutation in E1 gene region. 2278 21

Chikungunya virus (CHIKV) infection is characterized by rash, acute high fever, chills, headache, nausea, photophobia, vomiting, and severe polyarthralgia. There is evidence that arthralgia can persist for years and result in long-term discomfort. Neurologic disease with fatal outcome has been documented, although at low incidences. The CHIKV RNA genome encodes five structural proteins (C, E1, E2, E3 and 6K). The E1 spike protein drives the fusion process within the cytoplasm, while the E2 protein is believed to interact with cellular receptors and therefore most probably constitutes the target of neutralizing antibodies. We have constructed recombinant Modified Vaccinia Ankara (MVA) expressing E3E2, 6KE1, or the entire CHIKV envelope polyprotein cassette E3E26KE1. MVA is an appropriate platform because of its demonstrated clinical safety and its suitability for expression of various heterologous proteins. After completing the immunization scheme, animals were challenged with CHIV-S27. Immunization of AG129 mice with MVAs expressing E2 or E3E26KE1 elicited neutralizing antibodies in all animals and provided 100% protection against lethal disease. In contrast, 75% of the animals immunized with 6KE1 were protected against lethal infection. In conclusion, MVA expressing the glycoprotein E2 of CHIKV represents as an immunogenic and effective candidate vaccine against CHIKV infections.
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PMID:Recombinant modified vaccinia virus Ankara expressing glycoprotein E2 of Chikungunya virus protects AG129 mice against lethal challenge. 2518 30

Ebola virus disease (EVD) has been a great concern worldwide because of its high mortality. EVD usually manifests with fever, diarrhea and vomiting, as well as disseminated intravascular coagulation (DIC). To date, there is neither a licensed Ebola vaccine nor a promising therapeutic agent, although clinical trials are ongoing. For replication inside the cell, Ebola virus (EBOV) must undergo the proteolytic processing of its surface glycoprotein in the endosome by proteases including cathepsin B (CatB), followed by the fusion of the viral membrane and host endosome. Thus, the proteases have been considered as potential targets for drugs against EVD. However, no protease inhibitor has been presented as effective clinical drug against it. A synthetic serine protease inhibitor, nafamostat mesilate (NM), reduced the release of CatB from the rat pancreas. Furthermore, it has anticoagulant activities, such as inhibition of the factor VIIa complex, and has been used for treating DIC in Japan. Thus, NM could be considered as a drug candidate for the treatment of DIC induced by EBOV infection, as well as for the possible CatB-related antiviral action. Moreover, the drug has a history of large-scale production and clinical use, and the issues of safety and logistics might have been cleared. We advocate in vitro and in vivo experiments using active EBOV to examine the activities of NM against the infection and the DIC induced by the infection. In addition, we suggest trials for comparison among anti-DIC drugs including the NM in EVD patients, in parallel with the experiments.
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PMID:A Synthetic Serine Protease Inhibitor, Nafamostat Mesilate, Is a Drug Potentially Applicable to the Treatment of Ebola Virus Disease. 2634 67

Seeds of the castor bean plant Ricinuscommunis L (CB) contain ricin toxin (RT), one of the most poisonous naturally-occurring substances known. Ricin toxin, a water-soluble glycoprotein that does not partition into the oil extract, is a ribosome-inactivating toxin composed of two chains, labeled A and B. Severity of the toxicity varies depending on the route of exposure to the toxin. Inhalational is the most toxic route, followed by oral ingestion. Orally-ingested RT accumulates in the liver and spleen but other cells are also affected. The main clinical manifestations are also related to the administration route. Oral ingestion of CB or RT results in abdominal pain, vomiting, diarrhea, and various types of gastrointestinal bleeding that leading to volume depletion, hypovolemic shock, and renal failure. Inhalation of the toxin presents with non-cardiogenic pulmonary edema, diffuse necrotizing pneumonia, interstitial and alveolar inflammation, and edema. Local injection of RT induces indurations at the injection site, swelling of regional lymph nodes, hypotension, and death. An enzyme-linked immunosorbent assay (ELISA) has been developed to detect RT in animal tissues and fluids. Ricinine, an alkaloid of CB, can be detected in rat urine within 48 h of RT exposure. Supportive care is the basic treatment and standard biowarfare decontamination protocols are used for RT intoxication. Dexamethasone and difluoromethylornithine might be effective treatments. This review examines the clinical and molecular aspects of ricin toxicity.
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PMID:Ricin Toxicity: Clinical and Molecular Aspects. 2753 98


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