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

Long periods in space may expose astronauts to the potentially harmful effects of ionizing radiation. We have used a primate model to evaluate any role of lipopolysaccharide (LPS, endotoxin) in radiation sickness. Vervet monkeys, which had been whole-body 60Co irradiated with an LD100 exposure, had periodic blood samples taken for the determination of LPS, anti-LPS IgG antibodies and bacteriological studies. On day 2 post-irradiation, primates were treated i.m. with either sterile 0.9% saline, or equine anti-LPS hyperimmune plasma (Anti-LPS), or orally with tripotassium-dicitrato-bismuthate ("Denol"). Gram positive bacteria were evident in blood samples of all animals as early as 2 d post-irradiation. Gram negative bacteria were found in the blood of saline- and Denol-treated primates by days 5 and 8, respectively, but first appeared on day 13 in the anti-LPS-treated animals. The saline controls and Denol-treated animals showed insignificant rises in plasma LPS on day 3, which increased further thereafter achieving significance on day 8 (p less than 0.01). These elevated levels persisted until death. However, in anti-LPS-treated monkeys, LPS concentrations remained below baseline until day 9, after which they rose significantly until death, but, were significantly less than the concentrations in both other groups (p less than 0.001). The anti-LPS-treated animals survived significantly longer than both the other groups (p less than 0.005). Since LPS may cause nausea, vomiting, diarrhea, anorexia and headaches, Anti-LPS administration may be of value in reducing plasma LPS concentration in humans and improving their performance and survivability.
 ...
PMID:Anti-LPS antibodies reduce endotoxemia in whole body 60Co irradiated primates: a preliminary report. 224 44

Cisplatin suspension in Lipiodol (LPS) was prepared for the treatment of hepatocellular carcinoma by intra-hepatic arterial injection. In a rabbit liver cancer model, concentrations of cisplatin in tumor were more than 20 times higher than those in a nontumorous part of the liver at 5 min after LPS injection into the hepatic artery. Cisplatin at high concentrations was detected at 7 days after injection. The concentrations in other organs were lower except in the gall-bladder. In clinical trials for 71 patients with hepatocellular carcinoma, partial response was observed in 33 cases (46.5%) and minor response in 20 cases (28.2%). The survival rate was 77% at 6 month and 55% at one year. Although fever, nausea, vomiting and epigastralgia were observed as side effects, these were temporary. Acute gastroduodenal mucosal lesions, cholecystitis, pancreatitis, delayed jaundice and hepatic encephalopathy were observed as complications and super selective cannulation was necessary for their prevention.
 ...
PMID:[Intra-arterial injection of cisplatin suspension in Lipiodol (LPS) in the treatment of hepatocellular carcinoma]. 255 Dec 47

Endotoxins (lipopolysaccharides, LPS) are potent bacterial poisons always present within the intestines in considerable amounts. Several pathophysiological conditions such as hypovolaemia, hypoxia, intestinal ischaemia, burns and radiation lead to a breakdown in the barrier and depending upon the extent of the injury, endotoxins enter the systemic circulation in increasing amounts. Antibiotics do not inactivate the endotoxins which continue to exert their toxic effects leading to nausea, vomiting, diarrhoea, fever, disseminated intravascular coagulation, vascular collapse and organ failure. When nonabsorbable antibiotics are given prior to the insult, systemic endotoxaemia is prevented. Immunotherapy, using anti-lipopolysaccharide IgG, inactivates plasma endotoxins, destroys gram-negative bacteria and opsonises them and may become a major form of therapy. An outline of endotoxin and anti-lipopolysaccharide and its importance to the anaesthetist and intensive care specialist is presented.
 ...
PMID:Endotoxins and anti-endotoxins (their relevance to the anaesthetist and the intensive care specialist). 265 93

Aeromonas spp. are Gram-negative rods of the family Vibrionaceae. They are normal water inhabitants and are part of the regular flora of poiquilotherm and homeotherm animals. They can be isolated from many foodstuffs (green vegetables, raw milk, ice cream, meat and seafood). Mesophilic Aeromonas spp. have been classified following the AeroKey II system (Altwegg et al., 1990; Carnahan et al., 1991). The major human diseases caused by Aeromonas spp. can be classified in two major groups: septicemia (mainly by strains of A. veronii subsp. sobria and A. hydrophila), and gastroenteritis (any mesophilic Aeromonas spp. but principally A. hydrophila and A. veronii). Most epidemiological studies have shown Aeromonas spp. in stools to be more often associated with diarrhea than with the carrier state; an association with the consumption of untreated water was also conspicuous. Acute self-limited diarrhea is more frequent in young children, in older patients chronic enterocolitis may also be observed. Fever, vomiting, and fecal leukocytes or erythrocytes (colitis) may be present (Janda, 1991). The main putative virulence factors are: exotoxins, endotoxin (LPS), presence of S-layers, fimbriae or adhesins and the capacity to form capsules.
 ...
PMID:Emerging pathogens: Aeromonas spp. 875 Jun 64

The probable involvement of prostaglandins in the myoelectrical response of the antrum pylori and small intestine to endotoxin (LPS) was studied in the piglet. In these experiments the influence of I.V. infusion of PGF2 alpha and PGE2 and of I.V. injection of LPS, without and with indomethacin (INDO) pretreatment, on myoelectrical activity of the antrum pylori, duodenum, jejunum and ileum as well as on some clinical and haematological parameters was studied. Infusion of the 2 PG's, especially PGE2, inhibited myoelectrical activity of the antrum pylori. PGE2 also reduced duodenal activity. PGF2 alpha was without effect on duodenal and jejunal activity, but stimulated ileal activity. Both PG's induced fever, nausea, vomiting and sedation or excitation. With the higher dose of PGE2 diarrhoea was also observed. Injection of LPS induced identical myoelectrical and clinical changes, as described for PGE2. However, endotoxin did not induce diarrhoea. Depending on the dose, administration of LPS resulted in a leukocytosis or a leukopenia together with an increase in band neutrophils. Following pretreatment with INDO the effects of LPS on gastrointestinal electrical activity were reduced and its clinical symptoms were nearly completely inhibited. The haematological changes induced by LPS, however, were not influenced by INDO. These experiments suggest a possible involvement of the PG's in the clinical symptoms and in the initial inhibitory effect of LPS on myoelectrical activity especially of the antrum. However, the induced haematological changes are probably not mediated by the arachidonic acid pathway.
 ...
PMID:[The involvement of prostaglandins in the inhibiting effect of endotoxin on the myoelectric activity of the gastrointestinal system in pigs]. 915 44

This communication describes the synthesis and in vitro and in vivo evaluation of a novel potent series of phosphodiesterase type (IV) (PDE4) inhibitors. Several of the compounds presented possess low nanomolar IC50's for PDE4 inhibition and excellent in vivo activity for inhibition of TNF-alpha levels in LPS challenged mice (mouse endotoxemia model). Emesis studies (dog) and efficacy in a SCW arthritis model for the most potent PDE4 inhibitors are presented.
 ...
PMID:Orally active indole N-oxide PDE4 inhibitors. 987 75

The discovery and SAR of a new series of substituted 8-arylquinoline PDE4 inhibitors are herein described. This work has led to the identification of several compounds with excellent in vitro and in vivo profiles, including a good therapeutic window of emesis to efficacy in several animal models. Typical optimized compounds from this series are potent inhibitors of PDE4 (IC(50)<1nM) and also of LPS-induced TNF-alpha release in human whole blood (IC(50)<0.5microM). The same compounds are potent inhibitors of ovalbumin-induced bronchoconstriction in conscious guinea pigs (EC(50)<0.1mg/kg ip) but require a dose of about 10mg/kg po in the squirrel monkey to produce an emetic response. From this series of compounds, 23a (L-454,560) was identified as an optimized compound.
 ...
PMID:Discovery of a substituted 8-arylquinoline series of PDE4 inhibitors: structure-activity relationship, optimization, and identification of a highly potent, well tolerated, PDE4 inhibitor. 1616 47

Type 4 phosphodiesterases (PDE4) inhibitors are emerging therapeutics in the treatment of a number of chronic disorders including asthma, chronic obstructive pulmonary disease (COPD) and cognitive disorders. This study delineates the preclinical profile of L-454,560, which is a potent, competitive and preferential inhibitor of PDE4A, 4B, and 4D with IC50 values of 1.6, 0.5 and 1.2 nM, respectively. In contrast to the exclusive binding of cilomilast and the preferential binding of roflumilast to the PDE4 holoenzyme state (Mg2+-bound form), L-454,560 binds to both the apo-(Mg2+-free) and holoenzyme states of PDE4. The intrinsic enzyme potency for PDE4 inhibition by L-454,560 also results in an effective blockade of LPS-induced TNFalpha formation in whole blood (IC50 = 161 nM) and is comparable to the human whole blood potency of roflumilast. The cytokine profile of inhibition of L-454,560 is mainly a Th1 profile with significant inhibition of IFNgamma and no detectable inhibition of IL-13 formation up to 1 microM. L-454,560 was also found to be efficacious in two models of airway hyper-reactivity, the ovalbumin (OVA) sensitized and challenged guinea pig and the ascaris sensitized sheep model. Furthermore, L-454560 was also effective in improving performance in the delayed matching to position (DMTP) version of the Morris watermaze, at a dose removed from that associated with potential emesis. Therefore, L-454,560 is a novel PDE4 inhibitor with an overall in vivo efficacy profile at least comparable to roflumilast and clearly superior to cilomilast.
 ...
PMID:L-454,560, a potent and selective PDE4 inhibitor with in vivo efficacy in animal models of asthma and cognition. 1742 47

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.
 ...
PMID:Design, synthesis, and biological evaluation of 8-biarylquinolines: a novel class of PDE4 inhibitors. 1820 97

Shigella are gram-negative bacterium that cause bacillary dysentery (shigellosis). Symptoms include diarrhea and discharge of bloody mucoid stools, accompanied by severe abdominal pain, nausea, vomiting, malaise, and fever. Persons traveling to regions with poor sanitation and crowded conditions become particularly susceptible to shigellosis. Currently a vaccine for Shigella has not been licensed in the United States, and the organism quickly becomes resistant to medications. During the past 10 y, several live attenuated oral Shigella vaccines, including the strain WRSS1, have been tested in humans with considerable success. These Phase I vaccines lack the gene for the protein VirG also known as IcsA, which enables the organism to disseminate in the host target tissue. However, 5% to 20% of the vaccinated volunteers developed mild fever and brief diarrhea, and the removal of additional virulence-associated genes from the vaccine strain may reduce or eliminate these side effects. We administered 2 Shigella sonnei vaccines, WRSs2 and WRSs3, along with WRSS1 to compare their rates of colonization and clinical safety in groups of 5 rhesus macaques. The primate model provides the most physiologically relevant animal system to test the validity and efficacy of vaccine candidates. In this pilot study using a gastrointestinal model of infection, the vaccine candidates WRSs2 and WRSs3, which have additional deletions in the enterotoxin and LPS modification genes, provided better safety and comparable immunogenicity to those of WRSS1.
 ...
PMID:Safety and colonization of two novel VirG(IcsA)-based live Shigella sonnei vaccine strains in rhesus macaques (Macaca mulatta). 1979 62


1 2 Next >>