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PubMed1990

Analytical methods for Bacillus cereus and other Bacillus species.

Bacillus cereus can give rise to two distinct forms of foodborne disease, the emetic and the diarrhoeal syndromes. The emetic syndrome is believed to be associated with an emetic toxin pre-formed in food. Cooked rice is the most common vehicle, and the symptoms are similar to those of Staphylococcus aureus intoxication. The diarrhoeal type is caused by an enterotoxin and the symptoms generally parallel those of the Clostridium perfringens food poisoning. The heat resistance of B. cereus spores and the non-fastidious nature of the organism facilitates its survival and/or growth in a wide variety of foods. This review describes analytical methods available for the isolation, identification, and enumeration of the organism, in addition to details about biological and immunological methods for toxin assay. Data are also presented concerning the incidence and epidemiology of B. cereus food poisoning around the world, and especially in Japan.

Bacillus cereus↗
PubMed1984

Amitriptyline plus fluphenazine to prevent chemotherapy-induced emesis in cancer patients: a double-blind randomized cross-over study.

In a population of 51 ambulant cancer patients treated with doxorubicin-containing chemotherapy we conducted a double-blind cross-over randomized trial, comparing the anti-emetic efficacy of a combination of amitriptyline (25 mg p.o. q 6 hr X 4) and fluphenazine (2.5 mg p.o. q 6 hr X 4) (AF) with that of metoclopramide (20 mg q 6 hr X 4) (M). Thirty-three out of the 51 patients vomited less than six times during treatment with AF as opposed to 26/51 with M. This difference was not significant. However, 55% of patients preferred AF to M, compared to 30% with the reverse preference (P less than 0.1). The main side-effect was drowsiness, which patients reported significantly more frequently when on AF. With both anti-emetic regimens men vomited less frequently than women. The combination of amitriptyline and fluphenazine, though theoretically attractive, did not appear to be an effective anti-emetic regimen in the dose and schedule given.

Adult↗
PubMed1984

Emesis due to cancer chemotherapy: results of a prospective, randomised, double-blind trial of varying doses of metoclopramide in the management of cis-platinum-induced vomiting.

A randomised, double-blind prospective trial was conducted to determine the relative anti-emetic efficacy of three dose levels of metoclopramide in cancer patients receiving combination chemotherapy including cis-platinum. With consecutive courses of chemotherapy, 60 patients received doses of either 3,5 or 10 mg/kg metoclopramide (50, 54 or 55 courses respectively) in a randomly assigned sequence. Major control of emesis (less than or equal to 2 vomits) was achieved in 38% of 159 patient treatments. There were no significant differences in either anti-emetic efficacy or the incidence of side-effects between the three doses used. It is concluded that while metoclopramide is an effective anti-emetic for patients receiving cisplatinum therapy, no advantage accrues to the use of doses in excess of 3 mg/kg (total dose).

Adolescent↗
PubMed1991

Tropisetron plus haloperidol to ameliorate nausea and vomiting associated with high-dose alkylating agent cancer chemotherapy.

Tropisetron is a novel antiserotoninergic drug with potent and specific activity against cancer chemotherapy-induced emesis. High-dose cyclophosphamide or high-dose melphalan are chemotherapeutic regimens associated with severe nausea and vomiting refractory to current antiemetic medications. We compared in a randomised open label study the antiemetic efficacy of tropisetron and alizapride in a first group of 32 consecutive patients treated with high-dose alkylating agent chemotherapy with or without autologous bone marrow transplantation. Tropisetron was more effective than alizapride in reducing vomiting episodes. In the first 24 h of treatment the median number of episodes in patients treated with tropisetron was 5 compared with 9 episodes in the alizapride group (P = 0.005). In the 72 h study period the median number of emetic episodes was 6 in the tropisetron group and 12 in the alizapride group (P = 0.004). In a second group of 26 consecutive patients, a combination of tropisetron plus haloperidol, a dopamine antagonist, was employed for prevention of emesis. This combination was more effective than tropisetron as single agent in preventing emetic episodes, as the median number of emetic episodes in the 72 h of observation was only 3, while they were 6 in the tropisetron group. The side-effects of tropisetron were mild and reversible upon discontinuation of the drug. We conclude that tropisetron is an effective antiemetic drug when employed in high-dose alkylating agent chemotherapy, and that its activity is potentiated by the association with haloperidol.

Adult↗
PubMed1987

Evaluation of domperidone as a modifier of gamma-radiation-induced emesis.

The D2 antidopaminergic drug domperidone was evaluated, singly and in combination with synthetic adrenocorticoid and an H2 antihistamine, for its ability to reduce the acute emetic effects of 60Co whole-body radiation. Random-source adult male dogs were fasted 12 hr, fed a standard meal, injected 44 min later, and irradiated 47 min after that. Four groups of dogs were irradiated after drug injections as follows: saline (Con), domperidone (Dom), cimetidine + thiethylperazine (Cim + Thi), and dexamethasone + domperidone + cimetidine (Dex + Dom + Cim). Drug quantities given the dogs represented 10 mg Dom, 10 mg Thi, 20 mg Dex, and 300 mg Cim for an average human (70 kg, 1.8 m2). Subjects were exposed on an up-down schedule to determine the radiation necessary to produce vomiting in 50% (ED50) of each group. Emesis onset and offset times and number of episodes were recorded. The Dom group had more emetic episodes than any other. The Dex + Dom + Cim combination significantly raised the emetic threshold while maintaining episodes at a low incidence.

Animals↗
PubMed1986

Dimethylphenylpiperazinium-induced vomiting: nicotinic mediation in area postrema.

In unanesthetized cats the emetic action of dimethylphenylpiperazinium (DMPP) was investigated, after it was injected into the cerebral ventricles through chronically implanted cannulae. DMPP injected in 0.2-2.0 mg doses into the cerebral ventricle produced dose-dependent vomiting, which was abolished after ablation of area postrema. However, copper sulfate given intragastrically evoked vomiting in cats with an ablated area postrema. Further, the emetic response to ICV DMPP and to intragastric copper sulfate was depressed or abolished in cats pretreated with ICV reserpine. The emetic response to ICV DMPP, but not that caused by intragastric copper sulfate, was potentiated in cats pretreated with ICV 5,6-dihydroxytryptamine. Ganglionic blocking agents, mecamylamine and hexamethonium, injected ICV prevented the vomiting elicited by ICV DMPP. On the other hand, selected anti-muscarinic drugs, alpha and beta adrenergic antagonists, dopamine antagonists, antihistamines and a 5-hydroxytryptamine (5-HT) antagonist all injected into the cerebral ventricles had virtually no effect on the vomiting induced by DMPP. It is postulated that DMPP evokes vomiting by its action on nicotinic receptors of nerve cells within the area postrema but not on catecholaminergic, serotonergic, or cholinergic receptors. Finally, 5-HT and acetylcholine could also be involved in the inhibition of the complex mechanisms underlying the central regulation of vomiting.

Adrenergic alpha-Antagonists↗
PubMed1994

The connectivity of the area postrema in the ferret.

The area postrema (AP) is the chemosensitive trigger zone for the emetic reflex. We have investigated the connectivity of the AP and adjacent solitary complex (SC) to identify possible sites of the motor emetic center. The AP and SC were infused with HRP or WGA-HRP in 30 ferrets that were perfused transcardially after 24-72 h. A block from the pons to upper cervical spinal cord, and one with hypothalamus and basal forebrain, was cut at 50 microns, reacted, and mounted. Data support the conclusion, at variance with those from other preparations, that in ferrets the AP has reciprocal connections only with the SC, which serves as a relay in both ascending and descending pathways between AP and higher levels of the neuraxis. Connectivity of the SC with brain stem and forebrain structures including the rostral ventrolateral medulla, parabrachial nuclei, paraventricular nucleus, and amygdala was demonstrated. At least in ferrets, our results suggest that the motor emetic center must be located within the SC. While this may not apply to all species, it is also possible that some reports of AP projections elsewhere were results of label within the SC. Alternatively, the somewhat different pattern of emesis in the ferret as compared to the dog (greater role for vagal inputs in response to radiation and cytotoxic drugs, lesser role for humoral inputs) may reflect differences in AP connectivity.

Animals↗
PubMed1984

Production of enterotoxin(s) by Staphylococcus hyicus.

Five strains of Staphylococcus hyicus (3 of subspecies hyicus and 2 of chromogenes) were tested serologically for their ability to produce known and unknown enterotoxin(s) and were also examined using monkey bioassays. None of the 5 strains produced any detectable level of the known enterotoxins A--E. However, all of them produced emetic responses in 2 or more of 6 cynomologus monkeys when culture growth was fed intragastrically. One of the 5 strains (S. hyicus subspecies hyicus, VII 76) produced emetic responses in 3 of 6 monkeys with 50 ml of culture growth. The other 4 strains required 1 l of culture broth (concentrated 20-fold) to produce an emetic response in at least 2 of 6 monkeys. Enterotoxin production is, therefore, not unique to S. aureus species. Since some of these organisms do not produce coagulase and thermonuclease, they would be ignored in food hazard evaluation.

Animals↗
PubMed1996

An open randomised cross-over study on granisetron versus ondansetron in the prevention of acute emesis induced by moderate dose cisplatin-containing regimens.

The aim of the study was to compare granisetron (GRA) with ondansetron (OND) in the prevention of acute emesis in consecutive chemotherapy-naive patients admitted to our department to receive a cytotoxic treatment containing cisplatinum (CP) at a dose > or = 50 mg/m2. Eligible patients were randomised at their first cycle to receive either OND or GRA with cross-over of the anti-emetic treatment on the second cycle. The cytotoxic treatments included five different multidrug regimens containing CP (median dose 60 mg/m2, range 50-70 mg/m2) administered on day 1 and repeated every 21-28 days. OND was administered at the dose of 8 mg x 3 i.v. on day 1 and 8 mg x 2 orally on day 2. GRA was always administered at the dose of 3 mg i.v. on day 1. 124 patients entered the study. 58 patients received OND at their first cycle and 66 received GRA. Complete protection of acute emesis with OND and GRA was observed, with the first and second cycles combined as follows: nausea 53 and 60%, vomiting 68 and 71%, respectively (no statistically significant difference). The cross-over analysis comprising 101 patients confirmed no difference between the two anti-emetic treatments. 21 patients (19%) on OND and 14 patients (12%) on GRA suffered headaches (P = 0.15). 25 (25%) patients preferred OND, 45 (45%) preferred GRA, while 31 (30%) expressed no preference (P = 0.003). However, these differences also depended on the sequence of anti-emetics in the cross-over. In conclusion, in this study, a single dose of GRA is demonstrated to be as effective as multiple doses of OND in the prevention of acute emesis.

Acute Disease↗
PubMed2004

Strategies for postoperative nausea and vomiting.

Significant improvement towards a better control of postoperative nausea and vomiting have been achieved in recent years. Today, we understand better who is likely to vomit or to be nauseous after surgery. Significant amounts of the huge literature on anti-emetic interventions have been systematically reviewed, critically appraised and quantitatively synthesized. Thus, we know what anti-emetic interventions work, and how well they work, and we know their adverse effect profile. We also know which interventions have no worthwhile efficacy. A rational approach to postoperative nausea and vomiting includes three steps: identification of patients at risk, keeping the baseline risk low, and prophylactic administration of anti-emetics in those patients who are most likely to need them. For patients who are identified as high-risk patients, all measurements should be simultaneously initiated (multimodal anti-emesis).

Analgesics, Opioid↗
PubMed2004

Antiemetic effect of dexamethasone on cisplatin-induced early and delayed emesis in the pigeon.

We investigated the ability of dexamethasone to attenuate cisplatin (4 mg/kg, i.v.)-induced early and delayed emesis. These appear within the first 8-h period (early phase) and between 8 and 48 h (delayed phase), respectively, after cisplatin administration in the pigeon. Dexamethasone (0.1 and 1 mg/kg, i.m.) reduced significantly the number of emetic responses to cisplatin by 56% and 82% (P<0.05), respectively, in the early phase, and by 41% and 66% (P<0.05), respectively, in the delayed phase. Dexamethasone (1 and 10 microg/kg, i.c.v.) reduced the number of emetic responses by 66% and 91% (P<0.05), respectively, in the early phase, and by 56% and 87% (P<0.05), respectively, in the delayed phase. Indomethacin (10 mg/kg, i.m.) did not suppress cisplatin-induced early and delayed emesis. Dexamethasone (1 mg/kg, i.m.) did not affect the content of platinum in the medulla oblongata after cisplatin administration. The above results suggest that dexamethasone has antiemetic effects on both the early and delayed emetic responses to cisplatin in pigeons, partially via its central site of action, and that the antiemetic mechanism of dexamethasone is related to factors other than its inhibition of prostanoid synthesis or its membrane stabilizing effect which reduces influx of cisplatin into the medulla oblongata.

Animals↗
PubMed2005

Mode of action of gingerols and shogaols on 5-HT3 receptors: binding studies, cation uptake by the receptor channel and contraction of isolated guinea-pig ileum.

Ginger (rhizomes of Zingiber officinale) has been shown to exert potent anti-emetic properties, but its mode of action has not yet been elucidated. Among its active constituents, [6]-, [8]- and [10]-gingerol as well as [6]-shogaol were shown in different in vivo studies to be at least partly responsible for the drug's anti-emetic properties. In an attempt to gain more insight into the mode of action of these compounds, three different in vitro models were used to investigate their effects on 5-HT(3) receptors (serotonin receptor subtype) in more detail: [(14)C]guanidinium influx into N1E-115 cells which express 5-HT(3) receptors, isotonic contractions of the isolated guinea-pig ileum and equilibrium competition binding studies using a radioactively labeled 5-HT(3) receptor antagonist ([(3)H]GR65630) (3-(5-methyl-1H-imidazol-4-yl)-1-(1-methyl-1H-indol-3-yl)-1-propanone). All four compounds inhibited the [(14)C]guanidinium influx through 5-HT(3) receptor channels as well as contractions of the guinea-pig ileum induced by SR57227A ((4-amino)-(6-chloro-2-pyridyl)l-piperidine hydrochloride), a highly selective 5-HT(3) receptor agonist. Both effects were concentration-dependent, with the following order of potency for both models: [6]-shogaol> or =[8]-gingerol>[10]-gingerol> or =[6]-gingerol. All compounds showed also weak anticholinergic and antineurokininergic activities in the guinea-pig ileum (acetylcholine and substance P are mediators of the 5-HT(3) receptor effect). The vanilloid receptor did not seem to be involved derived from experiments using capsazepine. None of the tested ginger substances, however, was able to displace [(3)H]GR65630 from its binding site (5-HT(3) receptor) neither on intact N1E-115 cells nor on the purified membranes of HEK-293 cells over-expressing the h5-HT(3) receptor. It may be concluded that [6]-, [8]-, [10]-gingerol and [6]-shogaol exert their anti-emetic effect at least partly by acting on the 5-HT(3) receptor ion-channel complex, probably by binding to a modulatory site distinct from the serotonin binding site. This may include indirect effects via receptors in the signal cascade behind the 5-HT(3) receptor channel complex such as substance P receptors and muscarinic receptors; this needs further investigation since ginger is effective against motion sickness which is cured by some vanilloids and by anticholinergics such as scopolamine.

Animals↗
PubMed2006

Pharmacological MRI in awake rats reveals neural activity in area postrema and nucleus tractus solitarius: relevance as a potential biomarker for detecting drug-induced emesis.

Drug-induced vomiting (emesis) is a major concern in patient care and a significant hurdle in the development of novel therapeutics. With respect to the latter, rodents, such as the rat and mouse, are typically used in efficacy and safety studies; however, drug-induced emesis cannot be readily observed in these species due to the lack of an emetic reflex. It is known that emesis can be triggered by neural activity in brain regions including area postrema (AP) and nucleus tractus solitarius (NTS). In this study, using pharmacological magnetic resonance imaging (phMRI) and a blood-pool contrast agent, we imaged the hemodynamic consequences of brain activity in awake rats initiated by the administration of compounds (apomorphine 0.1, 0.3 micromol/kg i.v. and ABT-594 0.03, 0.1, 0.3 micromol/kg i.v.) that elicit emesis in other species. Regional drug-induced relative cerebral blood volume (rCBV) changes and percent activated area within the AP and NTS were calculated, in which a dose-dependent relationship was evident for both apomorphine and ABT-594. Additionally, to correlate with behavioral readouts, it was found that the activation of AP and NTS was observed at plasma concentrations consistent with those that induced emesis in ferrets for both drugs. Our data thus suggest that phMRI in awake rats may be a useful tool for predicting emetic liability of CNS-acting drugs and may provide insights into depicting the underlying emetic neural pathways in vivo.

Animals↗
PubMed2004

Investigation of impact of water type on borate ore flotation.

In this work, the impact of water type on borate ore flotation was investigated, while various physical parameters during flotation were considered in order to compare the results. Two different colemanite samples from Emet deposits of Turkey, named as Emet-A and Emet-B contained 44% B(2)O(3) and 40% B(2)O(3), respectively. The flotation tests were performed at feed particle size range of -210 +20 microm. Optimal consumption values for the reagents were determined as 2000 gt(-1) for AeroPromoter R825 from Cytec Company, a sulphonate type collector, 1500 gt(-1) for Procol CA927 from Allied Colloids Company, a sulphosuccinamate type collector and 100 gt(-1) for AeroFrother 70 from Cytec Company, an alcohol-type frother. In the tests, the impeller speed of the Denver-type flotation machine was set to 1200 rpm and the samples were fed into a litre cell at 25% solid/liquid ratio and at natural pH value of the slurry at room temperature. The flotation results obtained from the tests with use of tap water, demineralised water and the artificial water prepared with Ca(2+) and Mg(2+) cations deliberately added into demineralised water were compared to each other in optimal flotation conditions.

Borates↗
PubMed2001

Localization of phosphodiesterase-4 isoforms in the medulla and nodose ganglion of the squirrel monkey.

Pre-clinical and clinical studies are currently underway to evaluate the potential of phosphodiesterase-4 (PDE4) inhibitors for the treatment of chronic obstructive pulmonary disease and other inflammatory conditions of the airways. The most common side effect associated with this class of compounds is emesis. The squirrel monkey provides a model for evaluating the efficacy of PDE4 inhibitors and their emetic potential. The distribution of three PDE4 isoforms (A, C and D) has been investigated in the squirrel monkey medulla and nodose ganglion to determine which isoform(s) could be responsible for the emetic adverse effects. The distribution of PDE4 isoforms was delineated using immunohistochemistry with antibodies specific for PDE4A, PDE4C and PDE4D and by in situ hybridization with isoform-selective riboprobes. PDE4A was present in the medulla where expression was mostly restricted to glial cells and the vasculature. PDE4C was not detected in either the medulla or nodose ganglion. Finally, the PDE4D isoform was localized to neurons in the nodose ganglion and found through many structures of medulla including the area postrema, neurons of the nucleus tractus solitarius and locus coeruleus. These data are consistent with a role for PDE4D in the emetic response.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2002

The effect of serotonin and serotonin receptor antagonists on motion sickness in Suncus murinus.

In the present study, we investigated the effect of 5-hydroxytryptamine (5-HT) and 5-HT receptor agonists and antagonists on motion sickness in Suncus murinus, and the possibility that the emetic stimulus of 5-HT can alter the sensitivity of the animals to the different emetic stimulus of motion sickness. 5-HT (1.0, 2.0, 4.0 and 8.0 mg/kg ip) induced emesis and that was antagonised by methysergide (1.0 mg/kg ip), the 5-HT(4) receptor antagonist sulphamate[1-[2-[(methylsulphonyl)amino]ethyl]-4-piperidinyl]methyl-5-fluoro-2-methoxy-1H-indole-3-carboxylate (GR125487D; 1.0 mg/kg ip) and granisetron (0.5 mg/kg ip). Pretreatment with 5-HT caused a dose-related attenuation of the emetic response induced by a subsequent motion stimulus, which was not significantly modified by methysergide, granisetron or GR125487D pretreatment. (+)-1-(2,5-Dimethoxy-4-iodophenyl)-2-amino-propane (DOI; 0.5 and 1.0 mg/kg ip), 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT; 0.1 mg/kg ip) but not methysergide, GR125487D or granisetron, attenuated motion-induced emesis, and that was not affected by pretreatment with ketanserin (2.0 mg/kg, ip) or N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide trihydrocholoride (WAY-100635; 1.0 mg/kg ip), respectively. Indeed, ketanserin alone (0.1, 0.3, 1.0 and 2.0 mg/kg ip) attenuated motion sickness. These data indicate that 5-HT(1/2), 5-HT(3) and 5-HT(4) receptors are involved in the induction of 5-HT-induced emesis. However, agonist action at the 5-HT(1A/7) and 5-HT(2) receptors, and antagonist action at the 5-HT(2A) receptors can attenuate motion sickness in S. murinus.

Animals↗
PubMed2003

Granisetron versus granisetron/dexamethasone combination for the treatment of nausea, retching, and vomiting after major gynecologic surgery: a randomized, double-blind study.

BACKGROUND: Granisetron, a selective 5-hydroxytryptamine3 antagonist, is effective for the treatment of patients with postoperative nausea and vomiting. Dexamethasone decreases chemotherapy-induced emesis when added to an antiemetic regimen. OBJECTIVE: This study compared the efficacy of granisetron alone with granisetron/dexamethasone combination for the treatment of nausea and vomiting after major gynecologic surgery. METHODS: In this randomized, double-blind study, patients who were experiencing emetic symptoms during 0 to 3 hours after the end of anesthesia administration received granisetron 40 microg/kg i.v. either alone or in combination with dexamethasone 8 mg. Patients then were observed for 24 hours after study drug administration, with emetic episodes recorded and tolerability assessments performed by nursing staff blinded to treatment. RESULTS: A total of 120 women were enrolled (n = 60 in each treatment group; mean [SD] age in the granisetron group, 44 [9] years [range, 23-63 years]; combination group, 45 [8] years [range, 21-65 years]). No significant differences in patient demographic characteristics were found between the 2 treatment groups. However, the percentage of patients free of emetic symptoms (nausea, retching, vomiting) was higher in the granisetron/dexamethasone combination group than in the granisetron group (95.0% and 80.0%, respectively; P = 0.012). No clinically serious adverse events attributed to the study drugs were observed in either group. CONCLUSION: In this study, the granisetron/dexamethasone combination was more effective than was granisetron alone for the management of nausea and vomiting during 0 to 3 hours after anesthesia in women undergoing major gynecologic surgery.

Adult↗
PubMedDate not supplied

Efficacy and tolerability of oral ondansetron versus prochlorperazine in the prevention of emesis associated with cyclophosphamide-based chemotherapy and maintenance of health-related quality of life.

This study compared the efficacy and tolerability of oral ondansetron (8 mg twice daily [BID] for up to 3 days) with those of phenothiazine prochlorperazine (10 mg BID for up to 3 days) in 133 cancer patients receiving cyclophosphamide-based chemotherapy. In addition, the study evaluated the impact of these treatments on patients' health-related quality of life, measured with both the Functional Living Index--Cancer and the Functional Living Index--Emesis questionnaires. The first dose of study drug was administered 30 minutes before initiation of chemotherapy. Patients received a rescue antiemetic at their request or if the investigator deemed it necessary. There was a statistically significant difference in the number of patients with no emetic episodes over the 3-day study period: 60% in the ondansetron group compared with 21% in the prochlorperazine group. Twenty-five percent of ondansetron-treated patients compared with 68% of prochlorperazine-treated patients experienced three or more emetic episodes, rescue medication use, or withdrawal from the study due to adverse events or lack of efficacy of the study drug. Among patients with at least one emetic episode, the mean time to emesis was significantly longer (13 hours and 37 minutes) in the ondansetron group compared with the prochlorperazine group (9 hours and 30 minutes). Nausea and appetite scores did not differ significantly between groups. The score on the vomiting subscale of the Functional Living Index--Emesis was significantly more favorable in the ondansetron group compared with the prochlorperazine group, indicating better maintenance of health-related quality of life in ondansetron-treated patients. Both treatments were well tolerated. The most common potentially drug-related adverse event was headache, which occurred in significantly more (16%) ondansetron-treated patients compared with prochlorperazine-treated patients (3%). The results of this study demonstrate that oral ondansetron 8 mg BID for up to 3 days is more effective than prochlorperazine 10 mg BID for up to 3 days in the prevention of emesis associated with moderately emetogenic chemotherapy.

Adult↗