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)

Thirteen 3-week-old pigs that had been allowed to nurse for the first 16 to 18 hours after birth were orally inoculated with 1 x 10(6.5) TCID50 of porcine rotavirus. All developed diarrhea, anorexia, and vomiting by postinoculation (PI) hour 30. These signs had abated by PI day 6. Villus blunting in the small intestine was most severe in the jejunum and ileum of pigs euthanatized between PI days 3 and 5. Villi had returned to nearly normal length by PI day 6, although fused villi were seen in a few locations in the distal portion of the jejunum and in the ileum. Virus was detected in the feces of inoculated pigs by isolation in cell cultures and by electron microscopy during the 7-day course of the experiment. There was 1 extraintestinal virus isolation from the lung of 1 pig at PI day 2. Infection and disease developed in the presence of serum-neutralizing antibody obtained by nursing seropositive sows. There was no significant change in neutralizing antibody titers in the 3-week-old pigs over the course of the experiment. In this experimental work, a model to study rotavirus infection in 3-week-old pigs has been developed.
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PMID:Experimental rotavirus infection in three-week-old pigs. 255 35

Several series of N-(quinuclidin-3-yl)aryl and heteroaryl-fused pyridones were synthesized and evaluated for 5-HT3 receptor affinity. In the heteroaryl series, 2-(quinuclidin-3-yl)tetrahydropyrido-[4,3-b]indol-1-one (8a) and the 4,5-alkano-bridged analogues (14 and 15) displayed high 5-HT3 receptor affinity with pKi values > 9. The (3S)-quinuclidinyl isomers had > 10 fold higher affinity than the (3R)-isomers. In a series of 2-quinuclidin-3-yl)isoquinolin-1-ones, derivatives substituted with small lipophilic groups (25b-e) and with 4,5-alkano-bridges (34-36) also displayed high affinity. In particular, the hexahydro-1H-benz[de]isoquinolinone (S,S)-37 was the highest affinity 5-HT3 receptor ligand prepared (pKi 10.4). A number of the high affinity ligands were shown to be potent 5-HT3 receptor antagonists in vivo as determined by inhibition of the B-J reflex in the anesthetized rat. Again, (S,S)-37 was the most active agent tested (ID50 0.02 microgram/kg i.v.), and this compound was also potent in blocking cisplatin-induced emesis in both the ferret and the dog. Computer modeling studies were performed, and previously reported 5-HT3 receptor antagonist pharmacophore models were refined to include a key lipophilic binding domain.
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PMID:2-(Quinuclidin-3-yl)pyrido[4,3-b]indol-1-ones and isoquinolin-1-ones. Potent conformationally restricted 5-HT3 receptor antagonists. 841 Sep 77

The frequent occurrence of the eating disorder bulimia and major scientific contributions raise the question as to its origins, history, and course. Considerable information exists on bulimia. This paper reviews the historical references to the disorder from the first recorded report to the present (2,500 years ago to ca. 1970). The concept of bulimia has undergone various changes, beginning with a monosymptomatic, and leading to a polymorphous clinical picture. In addition, after being fused with the concept of kynorexia (incessant voracious eating followed by vomiting), the concept of bulimia has again attained a unified manifestation. Some symptoms appear to have taken on a different evaluation in time. All this must be seen in the context of the multiple changes which the concept of bulimia has undergone. Its characteristics justify neither a "new" disorder nor, as a consequence, an additional name.
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PMID:Bulimia: a historical outline. 895 22

We describe a case of sudden death caused by a rare complication of Crohn's disease. A 29-year-old man with Crohn's disease who had not taken medications regularly complained of nausea, vomiting, and abdominal pain for 2 days, and then died suddenly. Autopsy revealed protruding intestinal loops filled with gas, internal fistulas between fused loops of the terminal ileum, and complete obstruction of the fistulous tract. The histologic findings of transmural inflammation consisting of lymphocytic infiltration, accumulation of partially hyalinized collagen, and fibrosis in the skip areas from the ileum to the cecum were compatible with Crohn's disease. Furthermore, marked emaciation, atrophic change of the heart muscle, and diffuse fatty change of the liver were found. Although the patient died of obstructive ileus caused by a stricture produced by progression of Crohn's disease, he was severely affected by malnutrition which may have been fatal. This case not only illustrates that Crohn's disease can cause obstructive ileus and sudden death, but also makes the forensic pathologist realize the importance of suspecting the presence of an active inflammatory bowel disease in a patient with internal fistulas or malnutrition.
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PMID:Sudden death of a patient with Crohn's disease. 978 Jun 67

Congenital fusion of the maxilla and mandible (syngnathia) is rare and can present in a wide range of severity from single mucosal bands (synechiae) to complete bony fusion (synostosis). Congenital synostosis of the mandible and maxilla is even less common than synechiae, with only 25 cases reported in the literature. Most of them presented as an incomplete, unilateral fusion. A 4-year-old boy was referred to the authors' emergency unit with asphyxia after vomiting. The authors found the child could not open his mouth. His upper and lower jaws were fused, with only a 2- to 3-mm gap in the anterior part. X-rays and computed tomography scans showed that there was a bony fusion of the ramus of the mandible to the zygomatic complex and the posterior part of the maxilla. In addition, there was significant mandible hypoplasia. After performing an osteotomy (to treat the fusion between the bilateral ramus mandible, maxilla, and zygoma), the authors performed a temporomandibular joint reconstruction using a silicon block. After the completion of these procedures, they observed that the mouth could be opened 32 mm. After 2 years of mandibular lengthening performed with an external distracter, the patient's facial appearance and occlusion became more acceptable. An extremely rare case is described, and the existing literature is reviewed.
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PMID:Congenital fusion of the maxilla and mandible. 1575 Apr 27

IFN-gamma (interferon-gamma) has several applications in the treatment of IFN-gamma-related skin disorders. While systemic delivery - the major route used to administer IFN-gamma - results in significant side effects and toxicity, including fever, fatigue, nausea, vomiting and neurotoxicity, transdermal delivery has a very low transduction efficiency. In order to improve the efficiency of transdermal IFN-gamma delivery, we introduced a Pen (penetratin) peptide, a 16-amino-acid-long polypeptide corresponding to the third helix of the DNA-binding domain (homoeodomain) of Antennapedia (a Drosophila transcription factor). The human IFN-gamma gene was then fused with a gene fragment that encodes the Pen of Antennapedia in a bacterial expression vector, producing a genetic in-frame Pen-IFN-gamma. The expressed and purified Pen-IFN-gamma was then found to have a much more efficient transduction profile than native IFN-gamma. In addition, compared with native IFN-gamma, Pen-IFN-gamma exhibited similar activities when added exogenously to a culture medium: (i) induction of IRF-1 gene expression, and (ii) NF-kappaB (nuclear factor kappaB) luciferase reporter activation. These results indicate that the transdermal delivery system using Pen may be an excellent way to replenish IFN-gamma in the various disorders related to this cytokine.
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PMID:Transdermal delivery of interferon-gamma (IFN-gamma) mediated by penetratin, a cell-permeable peptide. 1580 34

Palonosetron is a 5-HT(3) receptor antagonist that has demonstrated superiority in preventing both acute and delayed emesis when compared to older first generation 5-HT(3) receptor antagonists. The objective of this work was to determine if palonosetron exhibits unique molecular interactions with the 5-HT(3) receptor that could provide a scientific rationale for observed clinical efficacy differences. Previously, we showed that palonosetron exhibits allosteric binding and positive cooperativity to the 5-HT(3) receptor in contrast to ondansetron and granisetron which exhibit simple bimolecular binding. The present work shows, through several independent experiments, that palonosetron uniquely triggers 5-HT(3) receptor internalization and induces prolonged inhibition of receptor function. After 24h incubation followed by dissociation conditions, [(3)H]palonosetron remained associated with whole cells but not to cell-free membranes (P<0.001). [(3)H]Palonosetron's binding to cells was resistant to both protease and acid treatments designed to denature cell surface proteins suggesting that the receptor complex was inside the cells rather than at the surface. Cells pretreated with unlabeled palonosetron subsequently exhibited reduced cell surface 5-HT(3) receptor binding. Palonosetron-triggered receptor internalization was visualized by confocal fluorescence microscopy using cells transfected with 5-HT(3) receptor fused to enhanced cyan fluorescent protein. In contrast, granisetron and ondansetron showed minimal to no effect on receptor internalization or prolonged inhibition of receptor function. These experiments may provide a pharmacological basis for differences noted in published clinical trials comparing palonosetron to other 5-HT(3) receptor antagonists.
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PMID:Palonosetron triggers 5-HT(3) receptor internalization and causes prolonged inhibition of receptor function. 1983 86

Deoxynivalenol (DON [vomitoxin]), one of trichothecene mycotoxins produced by the fungus Fusarium, is commonly detected in cereal foods across the world. DON induces diverse toxic effects in humans and animals, including emesis and diarrhea, anorexia, and immunotoxicity, and impaired maternal reproduction and fetal development. Recently, the teratogenic potential of DON has been shown and has received much attention. DON can cause various skeletal deformities in fetuses, but the underlying mechanisms have not yet been fully examined. In this study, fetal skeletal malformations in DON-treated maternal mice were thoroughly investigated using microarray assay. The results showed that DON administration caused various skeletal defects in fetuses, including misaligned or fused sternebrae and vertebrae, divided or fused ribs and polydactyly, hemivertebrae, short toes, and tail anomalies. Microarray analysis showed that 282 genes, including 148 downregulated and 134 upregulated genes, were abnormally expressed in fetal vertebral bones after maternal DON exposure. These identified genes can be classified into several categories: skeletal development, carcinogenesis, nervous disorders, sperm development and embryogenesis, and inflammation. Of these, 6 genes, mostly related to bone development, were intentionally selected for further validation using real-time reverse transcription-Polymerase Chain Reaction (RT-PCR). It was confirmed that the mRNA expression of 4 genes, i.e., fibrillin-1, Col9A2, 3'-phosphoadenosine 5'-phosphosulfate synthase 2, and Pax1, was upregulated significantly by DON administration, whereas that of 2 other genes, Runx2 and parathyroid hormone-like hormone, was downregulated significantly. Taken together, the results of our study suggest that altered expression of these 6 genes plays a critical role in fetal skeletal deformities induced by DON and thus they are worthy of further investigation.
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PMID:Evaluation of fetal skeletal malformations in deoxynivalenol-treated mice using microarray analysis. 2287 31

A micellar electrokinetic chromatography (MEKC) method was developed for the determination of three anti-vomiting drugs (aprepitant, dexamethasone and ondansetron) in pharmaceutical formulations. The method was optimized using a central composite design (CCD). Four main factors (borate buffer concentration, pH, methanol content and sodium dodecyl sulfate concentration) were optimized in order to obtain best resolutions and peak efficiencies in a minimum runtime. The separation was performed in a fused-silica capillary. After optimization, the background electrolyte consisted of a borate buffer (62.5mM, pH 8.75) containing sodium dodecyl sulfate (77.5mM) and methanol (3.75%). Under these conditions, a complete separation of each antiemetic drug and its respective internal standards was achieved in 38min. The method was validated with trueness values from 94.9 to 107.2% and precision results (repeatability and intermediate precision) lower than 5.9%. MEKC-UV was the first method allowing the separation of aprepitant, dexamethasone and ondansetron and was suitable for the quantitation of these three antiemetic drugs in organogel formulations. The rapid sample preparation coupled with an automated separation technique make this method convenient for quality control of extemporaneous magistral ready-to-use formulation.
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PMID:A validated micellar electrokinetic chromatography method for the quantitation of dexamethasone, ondansetron and aprepitant, antiemetic drugs, in organogel. 2397 40

A seven-month-old, entire, male miniature schnauzer dog was referred with acute vomiting, inappetence and depression primarily as a result of a gastric foreign body (pine cones). During investigations, thoracic radiographs revealed increased volume of the right lung lobes, deviated cardiomediastinal structures and elevation of the heart from the sternum. Thoracic computed tomography revealed left cranial lung lobe hypoplasia and extension of the right cranial lung parenchyma across the midline to the left hemithorax. Branches of the right pulmonary vessels and bronchi also crossed the midline and extended to the left caudal lung lobe. These findings suggested that the right and left lungs were fused. In humans this finding is consistent with horseshoe lung, which is an uncommon congenital malformation. To the authors' knowledge, this case represents the first report of such a pulmonary anomaly in a dog.
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PMID:Unusual congenital pulmonary anomaly with presumed left lung hypoplasia in a young dog. 2462 9


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