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PubMed1990

Apomorphine-induced emesis in the dog--routes of administration, efficacy and synergism by naloxone.

Apomorphine proved to be more effective as an emetic in dogs after s.c. administration than after i.m. injection with doses of 0.04 and 0.1 mg/kg. This effect is explained by an anti-emetic effect mediated by mu-receptors in the vomiting centre in the brain, which, in contrast to the chemoreceptor trigger zone, is within the blood-brain barrier. A certain delay between the stimulation of D2-receptors in the chemoreceptor trigger zone (causing emesis) and mu-receptors in the vomiting centre (producing anti-emesis) therefore results, leading to a self-limiting emesis. Blockade of the mu-receptors by naloxone increased and prolonged the effect of apomorphine. A relatively narrow range of apomorphine concentrations on s.c. administration is then effective to stimulate the chemoreceptor trigger zone, but can hardly inhibit the vomiting centre, and must therefore be considered the most suitable route for administration of apomorphine.

Animals↗
PubMed1991

Premedication before elective breast surgery, a comparison between ketobemidone and midazolam.

One hundred female patients scheduled for elective breast surgery (mean age 60 +/- 11 years were randomly assigned to receive one of two premedications: ketobemidone (Ketogan) 1-1.5 ml or midazolam 4-5 mg, intramuscularly. The effects on preoperative anxiety and postoperative emetic sequelae were studied. All patients were anaesthetised with thiopentone, fentanyl and atracurium, and ventilated with a mixture of nitrous oxide in oxygen with supplementary isoflurane. Sixty-nine percent of the midazolam- and 50% of the ketobemidone-premedicated patients experienced a reduction in anxiety. Midazolam was found to be more effective than ketobemidone in reducing anxiety among more tense patients--those with a VAS grading before premedication of 2 or more (P less than 0.05). Midazolam-premedicated patients were also assessed by observers as being more relaxed (P less than 0.05). No difference was seen in the frequency of emetic sequelae: 20 patients in the midazolam group and 14 patients in the ketobemidone group vomited once or more during the 24-h observation period. There was no difference between the two groups in time until an analgetic was required. In conclusion, midazolam seemed more effective in reducing preoperative anxiety than ketobemidone without any negative effects on postoperative emesis or time until an analgetic was required.

Aged↗
PubMed1994

Postoperative nausea and vomiting. A comparison between intravenous and inhalation anaesthesia in breast surgery.

Nausea and vomiting during the first 24 postoperative hours after breast surgery were studied. Ninety patients scheduled for elective breast surgery were randomly assigned to one of three anaesthetic methods: total intravenous anaesthesia with propofol, or propofol or thiopental for induction followed by isoflurane anaesthesia. All three groups received fentanyl for peroperative analgesia. A total of 46 (51%) patients experienced emetic sequelae: 19 (21%) complained about nausea and another 27 (30%) vomited once or more during the postoperative course. More than 50% of the patients with nausea and 70% with vomiting first suffered from these symptoms in the surgical wards after leaving the postoperative unit. Nausea and vomiting were seen in 18 (60%), 13 (43%) and 15 (50%) for the groups propofol-propofol, propofol-isoflurane and thiopental-isoflurane, respectively. In conclusion, every second patient experienced nausea or vomiting after breast surgery, the majority of these emetic symptoms occurring after leaving the postoperative unit. Propofol for induction or as a main anaesthetic did not make any major difference with regard to postoperative nausea or vomiting.

Aged↗
PubMed1997

Intravenous dolasetron and ondansetron in prevention of postoperative nausea and vomiting: a multicenter, double-blind, placebo-controlled study.

BACKGROUND: Intravenous dolasetron mesilate has shown efficacy in the prevention of postoperative nausea and vomiting (PONV) when administered as a single dose prior to emergence from anesthesia. This trial compared intravenous dolasetron and ondansetron for the prevention of PONV when administered at induction of anesthesia. METHODS: This double-blind, placebo-controlled, multicenter trial randomized patients to one of four single IV treatments placebo, 25 or 50 mg dolasetron, or 4 mg ondansetron. Efficacy was measured by complete response (0 emetic episodes and no rescue medication), nausea severity and patient satisfaction as measured on a visual analog scale (VAS), investigator's rating, of nausea severity, and total response (complete response with no nausea [< or = 5 mm VAS]). RESULTS: 514 patients at 24 sites were evaluated for efficacy. The 50 mg dolasetron and 4 mg ondansetron doses were statistically equivalent, and superior to placebo, for all efficacy measures. Complete response rates were 49%, 51%, 71% and 64% for placebo, 25 and 50 mg dolasetron, and ondansetron, respectively. Dolasetron 50 mg was statistically superior to 25 mg dolasetron for complete response, total response, VAS maximum nausea, time to first emetic episode, and patient satisfaction. The majority of adverse events were of mild-to-moderate intensity. Headache was the most frequently reported treatment-related adverse event with a 3%-5% incidence across treatments. CONCLUSION: When given at induction of anesthesia, 50 mg intravenous dolasetron is equivalent to 4 mg ondansetron and superior to 25 mg dolasetron and placebo for the prevention of PONV. All treatments were safely administered and well tolerated.

Adult↗
PubMed2000

Vomiting and common paediatric surgery.

Postoperative vomiting is a common and unpleasant complication. The purpose of the present study was to verify if dexamethasone reduces the incidence of vomiting when injected IV in children anaesthetized with halothane for common paediatric operations. We also studied the incidence of vomiting when sevoflurane was used instead. Five hundred and 69 boys, aged 2-12 years (ASA physical status I, II), scheduled for inguinal field surgery were randomly assigned to receive halothane, halothane and dexamethasone and sevoflurane in three groups: halothane (n=180), halothane and IV dexamethasone (n=188) and sevoflurane (n=201). Anaesthesia was induced by inhalation of halothane or sevoflurane in oxygen and nitrous oxide and was maintained at minimum alveolar concentration of each agent throughout the surgery. For intra- and postoperative pain control iliac crest block was used in all the boys. Vomiting was defined as any expulsion of liquid gastric contents. The incidence of postoperative vomiting was 23% in the halothane group, which was significantly greater than that in the other groups (halothane and dexamethasone group, 9%; sevoflurane group, 13%). In conclusion, dexamethasone reduces the incidence and frequency of multiple emetic episodes when administered intravenously after halothane anaesthesia; sevoflurane reduces the overall incidence of vomiting, but not multiple emetic episodes.

Anesthetics, Inhalation↗
PubMed1989

5-HT3 receptor antagonists injected into the area postrema inhibit cisplatin-induced emesis in the ferret.

1. The purpose of the present study was to identify and investigate the role of 5-hydroxytryptamine3 (5-HT3) receptors in the area postrema in the control of cisplatin-induced emesis in the ferret. 2. Homogenate binding and autoradiography experiments using the high affinity 5-HT3 receptor ligand, [3H]-GR65630, identified the presence of a high concentration of 5-HT3 receptors in the area postrema of the ferret. 3. Intraperitoneal injection of the 5-HT3 receptor antagonists, GR38032F, GR65630A and MDL72222, at doses of 1, 0.1 and 1 mg kg-1 respectively, inhibited emesis induced by cisplatin, 9 mg kg-1 i.p. 4. Discrete injection of low doses of the 5-HT3 receptor antagonists directly into the area postrema region also inhibited cisplatin-induced (9 mg kg-1 i.p.) emesis. The dose ranges used were: GR38032F, 0.01-1 microgram; GR65630A, 0.001-0.1 microgram; MDL72222, 0.1-10 micrograms. 5. Cisplatin-induced emesis was not inhibited by discrete injection of ketanserin (30 micrograms) or methiothepin (30 micrograms) into the area postrema. Injection of the 5-HT3 receptor agonist, 2-methyl-5-HT, directly into the area postrema produced an incomplete emetic response. 6. These results confirm a role of 5-HT, and in particular 5-HT3 receptors, in the control of cisplatin-induced emesis, and show that at least one functional site for these receptors in modulating the emetic response is the area postrema, the locus of the chemoreceptor trigger zone.

Animals↗
PubMed1995

Pharmacological characterization of RS 25259-197, a novel and selective 5-HT3 receptor antagonist, in vivo.

1. The pharmacological effects in vivo, of RS 25259-197, a selective 5-HT3 receptor antagonist, have been investigated. 2. In anaesthetized rats, RS 25259-197, administered by the intravenous, intraduodenal or transdermal route, dose-dependently inhibited the von Bezold-Jarisch reflex induced by 2-methyl 5-HT (ID50 = 0.04 micrograms kg-1, i.v., 3.2 micrograms kg-1, i.d. and 32.8 micrograms per chamber, respectively). In this regard, when administered intraduodenally, RS 25259-197 was more potent and exhibited a longer duration of action than either ondansetron or granisetron. 3. In conscious ferrets, RS 25259-197, administered intravenously or orally, dose-dependently inhibited emesis induced by cisplatin. The ID50 estimates of RS 25259-197 were 1.1 micrograms kg-1, i.v. and 3.2 micrograms kg-1, p.o. In this respect, RS 25259-197 was more potent than ondansetron and equipotent with granisetron. 4. In conscious dogs, RS 25259-197, administered intravenously or orally, dose-dependently inhibited emesis induced by cisplatin (ID50 = 1.9 micrograms kg-1, i.v. and 8.5 micrograms kg-1, p.o.), dacarbazine (ID50 = 4.1 micrograms kg-1, i.v. and 9.7 micrograms kg-1, p.o.), actinomycin D (ID50 = 4.9 micrograms kg-1, i.v. and 2.5 micrograms kg-1, p.o.) and mechlorethamine (ID50 = 4.4 micrograms kg-1, i.v. and 3.0 micrograms kg-1, p.o.). Against each of the emetogenic agents, RS 25259-197 was very much more potent than ondansetron. When tested at equi-effective intravenous doses against cisplatin-induced emesis in dogs, RS 25259-197 had a longer duration of anti-emetic activity (7 h) than ondansetron (4 h). At doses up to and including 1000 microg kg-1, p.o., neither RS25259-197 nor ondansetron was capable of inhibiting apomorphine-induced emesis.5. At doses up to 1000 microg kg-1, i.v., RS 25259-197 produced no meaningful haemodynamic changes in anaesthetized dogs.6. In summary, RS 25259-197 is a novel, highly potent and orally active 5-HT3 receptor antagonist in vivo. With respect to its anti-emetic activity, RS 25259-197 appears to be a significant improvement over ondansetron in terms of potency and duration of action.

Administration, Oral↗
PubMed1997

Bacillus cereus and its food poisoning toxins.

Bacillus cereus is becoming one of the more important causes of food poisoning in the industrialised world. It produces one emetic toxin and three different enterotoxins. The emetic toxin is a ring-shaped structure of three repeats of four amino and/or oxy acids: [D-O-Leu-D-Ala-L-O-Val-L-Val]3. This ring structure has a molecular mass of 1.2 kDa, and is chemically closely related to the potassium ionophore valinomycin. Two of the three enterotoxins have been shown to be involved in food poisoning. They both consist of three different proteins that act together. One of these enterotoxins is also a haemolysin. This haemolytic enterotoxin is transcribed from one operon. The third enterotoxin is a single component protein, but has not been shown to be involved in food poisoning.

Amino Acid Sequence↗
PubMed2004

Intermediate dose metoclopramide is not more effective than standard dose metoclopramide for patients who present to the emergency department with nausea and vomiting: a pilot study.

OBJECTIVE: To determine whether intermediate dose metoclopramide is more effective than standard dose metoclopramide for patients who present to the ED with nausea and vomiting. METHODS: This prospective, single-blind, randomized trial was conducted in the ED of two community teaching hospitals in a convenience sample of adult patients who presented to ED with nausea and vomiting. Patients were randomized to receive either 10 mg metoclopramide IV or 0.4 mg/kg IV (up to a maximum dose of 32 mg). The outcomes measured were: change in nausea score (measured on a 11-point verbal rating scale), requirement for other anti-emetic drug administration, and presence of side-effects. RESULTS: Fifty-eight patients were eligible for analysis (34 in 10 mg group and 24 in 0.4 mg/kg group). Median reduction in nausea score in 10 mg group was four (range 0-10, 95% CI 3-5) compared with five for 0.4 mg/kg group (range -1-10, 95% CI 4-6). This difference was not statistically significant (P = 0.629). Five patients in the 10 mg group required rescue anti-emetic, compared with three in the 0.4 mg/kg group (P = 1.00). There were no side-effects in the 10 mg group and two in the 0.4 mg/kg group. CONCLUSION: This study suggests that there is no difference in effectiveness between 10 mg and 0.4 mg/kg of metoclopramide in the ED population with nausea and vomiting.

Adolescent↗
PubMed1988

The role of the abdominal visceral innervation and 5-hydroxytryptamine M-receptors in vomiting induced by the cytotoxic drugs cyclophosphamide and cis-platin in the ferret.

We have used the ferret as an animal model to investigate the emetic action of the cytotoxic drugs cyclophosphamide and cis-platin. Using selective nerve lesions, a crucial role for the abdominal innervation in the genesis of retching and vomiting in response to these agents has been demonstrated. A combination of bilateral abdominal vagotomy and greater splanchnic nerve section can totally abolish retching and vomiting in response to intraperitoneal cis-platin or intravenous cyclophosphamide. Intraperitoneal cyclophosphamide still produced retching but vomiting was markedly reduced, demonstrating complex and probably separate control mechanisms for retching and vomiting. The effect of a widely used anti-emetic, metoclopramide, was compared to that of nerve lesions. While effective this compound did not totally control retching or vomiting to either drug. Recent studies have attributed metoclopramide's action to its ability to antagonize 5-HT M-receptors (5-HT-3 receptors). Therefore we investigated BRL 24924, a gastro-kinetic agent with more specific 5-HT M-receptor antagonist properties. This agent was extremely potent in almost totally abolishing retching and vomiting in response to cyclophosphamide, given by either an intravenous or intraperitoneal route, and totally abolished cis-platin-induced vomiting for at least 4 h. Clearly the abdominal visceral innervation plays a complex and major role in the emesis produced by these two cytotoxic drugs; circumstantial evidence suggests that 5-HT M-receptors on visceral afferent nerves mediate this action, but other possibly central sites of action of the 5-HT M-receptor antagonists cannot be excluded.

Animals↗
PubMed1995

Identification and purification of a new staphylococcal enterotoxin, H.

A staphylococcal enterotoxin which elicited an emetic response in monkeys but did not share antigenic determinants with any of the identified enterotoxins was identified and purified from Staphylococcus aureus FRI-569. The emetic activity of this new enterotoxin was neutralized only by antibodies specific to it and not by antibodies to enterotoxins A, B, C, D, and E or toxic shock syndrome toxin 1. Immunodiffusion assays did not detect cross-reactivity between this new and all the other identified enterotoxins. The purification procedure involved removal of the enterotoxin from culture supernatant fluids by batch adsorption with CG-50 resin, CM-Sepharose FL ion-exchange chromatography, and Sephacryl 100 HR and Bio-Gel P-30 gel filtration. The molecular weight of this enterotoxin, 27,300, determined by gel filtration on Sephacryl 100 HR agreed with the molecular weight, 28,500, determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The apparent migration of this enterotoxin determined by SDS-PAGE did not shift in the presence of a disulfide reducing agent, indicating that it is composed of a single-chain protein. The N-terminal amino acid sequence of the enterotoxin was determined to be Glu-Asp-Leu-His-Asp-Lys-Ser-Glu-Leu-Thr-Asp-Leu-Ala-Leu-Ala-Asn-Ala-Tyr- Gly- Gln-Tyr-Asn-His-Pro-Phe-Ile-Lys-Glu-Asn-Ile, which did not match the N-terminal sequences of any known proteins. The isoelectric point of the enterotoxin determined by isoelectric focusing was about 5.7.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Bacillus cereus and related species.

Bacillus cereus is a gram-positive aerobic or facultatively anaerobic spore-forming rod. It is a cause of food poisoning, which is frequently associated with the consumption of rice-based dishes. The organism produces an emetic or diarrheal syndrome induced by an emetic toxin and enterotoxin, respectively. Other toxins are produced during growth, including phospholipases, proteases, and hemolysins, one of which, cereolysin, is a thiol-activated hemolysin. These toxins may contribute to the pathogenicity of B. cereus in nongastrointestinal disease. B. cereus isolated from clinical material other than feces or vomitus was commonly dismissed as a contaminant, but increasingly it is being recognized as a species with pathogenic potential. It is now recognized as an infrequent cause of serious nongastrointestinal infection, particularly in drug addicts, the immunosuppressed, neonates, and postsurgical patients, especially when prosthetic implants such as ventricular shunts are inserted. Ocular infections are the commonest types of severe infection, including endophthalmitis, panophthalmitis, and keratitis, usually with the characteristic formation of corneal ring abscesses. Even with prompt surgical and antimicrobial agent treatment, enucleation of the eye and blindness are common sequelae. Septicemia, meningitis, endocarditis, osteomyelitis, and surgical and traumatic wound infections are other manifestations of severe disease. B. cereus produces beta-lactamases, unlike Bacillus anthracis, and so is resistant to beta-lactam antibiotics; it is usually susceptible to treatment with clindamycin, vancomycin, gentamicin, chloramphenicol, and erythromycin. Simultaneous therapy via multiple routes may be required.

Bacillaceae Infections↗
PubMed1991

The carboxyl-terminal region of staphylococcal enterotoxin type A is required for a fully active molecule.

Staphylococcal enterotoxin type A (SEA) gene (sea+) mutations were constructed by exonuclease III digestion or cassette mutagenesis. Five different sea mutations that had 1, 3, 7, 39, and 65 codons deleted from the 3' end of sea+ were identified and confirmed by restriction enzyme and nucleotide sequence analyses. Each of these sea mutations was constructed in Escherichia coli and transferred to Staphylococcus aureus by using the plasmid vector pC194. Culture supernatants from the parent S. aureus strain that lacked an enterotoxin gene (negative controls) and from derivatives that contained either sea+ (positive control) or a sea mutation were examined for in vitro sensitivity to degradation by monkey stomach lavage fluid, the ability to cause emesis when administered by an intragastric route to rhesus monkeys, and the ability to induce T-cell proliferation and by Western immunoblot analysis and a gel double-diffusion assay with polyclonal antibodies prepared against SEA. Altered SEAs corresponding to the predicted sizes were visualized by Western blot analysis of culture supernatants for each of the staphylococcal derivatives that contained a sea mutation. The altered SEA that lacked the C-terminal amino acid residue behaved like SEA in all of the assays performed. The altered SEA that lacked the three C-terminal residues of SEA caused T-cell proliferation but was not emetic; this altered SEA was degraded in vitro by monkey stomach lavage fluid and did not reach in the gel double diffusion assay. Altered SEAs that lacked 7, 39, or 65 carboxyl-terminal residues were degraded by stomach lavage fluid in vitro, did not produce an emetic response, and did not induce T-cell proliferation or form a visible reaction in the gel double-diffusion assay.

Amino Acid Sequence↗
PubMed1998

Identification and characterization of staphylococcal enterotoxin types G and I from Staphylococcus aureus.

Staphylococcal enterotoxins are exotoxins produced by Staphylococcus aureus that possess emetic and superantigenic properties. Prior to this research there were six characterized enterotoxins, staphylococcal enterotoxin types A to E and H (referred to as SEA to SEE and SEH). Two new staphylococcal enterotoxin genes have been identified and designated seg and sei (staphylococcal enterotoxin types G and I, respectively). seg and sei consist of 777 and 729 nucleotides, respectively, encoding precursor proteins of 258 (SEG) and 242 (SEI) deduced amino acids. SEG and SEI have typical bacterial signal sequences that are cleaved to form toxins with 233 (SEG) and 218 (SEI, predicted) amino acids, corresponding to mature proteins of 27,043 Da (SEG) and 24,928 Da (SEI). Biological activities for SEG and SEI were determined with recombinant S. aureus strains. SEG and SEI elicited emetic responses in rhesus monkeys upon nasogastric administration and stimulated murine T-cell proliferation with the concomitant production of interleukin 2 (IL-2) and gamma interferon (IFN-gamma), as measured by cytokine enzyme-linked immunoassays. SEG and SEI are related to other enterotoxins of S. aureus and to streptococcal pyrogenic exotoxin A (SpeA) and streptococcal superantigen (SSA) of Streptococcus pyogenes. Phylogenetic analysis and comparisons of amino acid and nucleotide sequence identities were performed on related staphylococcal and streptococcal protein toxins to group SEG and SEI among the characterized toxins. SEG is most similar to SpeA, SEB, SEC, and SSA (38 to 42% amino acid identity), while SEI is most similar to SEA, SEE, and SED (26 to 28% amino acid identity). Polyclonal antiserum was generated against purified histidine-tagged SEG and SEI (HisSEG and HisSEI). Immunoblot analysis of the enterotoxins, toxic-shock syndrome toxin 1, and SpeA with antiserum prepared against HisSEG and HisSEI revealed that SEG shares some epitopes with SEC1 while SEI does not.

Amino Acid Sequence↗
PubMed2005

Characterization of novel staphylococcal enterotoxin-like toxin type P.

We investigated the biological properties of a novel staphylococcal enterotoxin (SE)-like toxin type P (SElP). SElP induced a substantial proliferative response and the production of cytokines interleukin-2, gamma interferon, tumor necrosis factor alpha, and interleukin-4 from human T cells when administered at a concentration of 0.4 pM (0.01 ng/ml) or more. The expression of major histocompatibility complex class II molecules on accessory cells was required for T-cell stimulation by SElP. SElP selectively stimulated a vast number of human T cells bearing receptors Vbeta 5.1, 6, 8, 16, 18, and 21.3. These results indicated that SElP acts as a superantigen. SElP proved to be emetic in the house musk shrew emetic assay, although at a relatively high dose (50 to 150 mug/animal). A quantitative assay of SElP production with 30 Staphylococcus aureus strains harboring selp showed that 60% of these strains produced significant amounts of SElP in vitro. All 10 strains carrying seb and selp produced SEB but not SElP, suggesting the inactivation of the selp locus in S. aureus strains with a particular se gene constitution.

Animals↗
PubMed1990

Mechanics of vomiting: a minireview.

In a cineradiographic analysis of the vomiting reflex in response to i.v. administration of an emetic drug (lanatoside C, 12 mg/kg) in cats, it was shown that the vomiting act is preceded by cyclic periods of abnormal peristaltic activity of the small bowel and inhibition of gastric peristalsis. It was further observed that massive antiperistalsis of the upper small bowel with reflux into the stomach is a common occurrence in the period immediately preceding vomiting. The emetic act itself is composed of phases of esophageal dilation, gastric emptying, gastric reflux, and esophageal collapse in cyclic repetition. The response of the esophagus and the stomach during emesis is passive, with external pressures and forces apparently providing the expulsive forces, the gastric bolus being contained by contraction of the pylorus and probably an upper esophageal or pharyngeal barrier. Earlier studies were conducted in cats in which observations were made on changes in thoracic venous pressure, abdominal venous pressure, and arterial blood pressure associated with vomiting induced by Veratrum alkaloids. Retching was characterized by a growing series of brief negative intrathoracic pressure pulses mirrored by positive pressure pulses in the abdomen. Expulsion then occurred and was followed with a sudden reversal of intrathoracic pressure from negative to positive. Expulsion involved a more sustained abdominal contraction, but both retching and expulsion were brought about by the same set of muscles, according to their EMG profiles. From results observed following phrenicotomy and spinal cord section at T5, it was concluded that the diaphragm, acting together with the inspiratory muscles against a closed glotis is responsible for the negative intrathoracic pressure that occurs in retching.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Effects of ganoderma lucidum extract on chemotherapy-induced nausea and vomiting in a rat model.

Chemotherapy is highly cytotoxic, causing a number of severe adverse effects such as nausea and vomiting. Herbal medicines, which can often be used on a daily basis for prolonged treatment, may be clinically beneficial. Ganoderma lucidum or Lingzhi mushroom has been recognized as a remedy in treating a number of medical conditions, including balancing immunity and decreasing drug-induced side effects. It has been shown that rats react to emetic stimuli, like the chemotherapy agent cisplatin, by increased consumption of kaolin, known as pica; and this rat model has been utilized to evaluate novel anti-emetic compounds. In this study, we evaluated the effects of a G. lucidum extract (SunRecome, the most commonly used Lingzhi mushroom extract in China) in attenuating cisplatin-induced nausea and vomiting in the rat pica model. We observed that intraperitoneal cisplatin injection caused a significant increase in kaolin intake at 24, 48, 72 and 96 hours, reflecting cisplatin's nausea and vomiting action. This cisplatin-induced kaolin intake dose-dependently decreased after 1, 3 and 10 mg/kg G. lucidum extract injection (p < 0.01). In addition, there was a significant reduction of food intake after cisplatin. The cisplatin-induced food intake reduction improved significantly after G. lucidum extract administrations in a dose-related manner (p < 0.01), suggesting a supportive effect of the extract on general body condition. Future controlled clinical trials are needed to evaluate the safety and effectiveness of this herbal medication.

Animals↗
PubMed2003

Delta9-tetrahydrocannabinol selectively acts on CB1 receptors in specific regions of dorsal vagal complex to inhibit emesis in ferrets.

The aim of this study was to investigate the efficacy, receptor specificity, and site of action of Delta9-tetrahydrocannabinol (THC) as an antiemetic in the ferret. THC (0.05-1 mg/kg ip) dose-dependently inhibited the emetic actions of cisplatin. The ED50 for retching was approximately 0.1 mg/kg and for vomiting was 0.05 mg/kg. A specific cannabinoid (CB)1 receptor antagonist SR-141716A (5 mg/kg ip) reversed the effect of THC, whereas the CB2 receptor antagonist SR-144528 (5 mg/kg ip) was ineffective. THC applied to the surface of the brain stem was sufficient to inhibit emesis induced by intragastric hypertonic saline. The site of action of THC in the brain stem was further assessed using Fos immunohistochemistry. Fos expression induced by cisplatin in the dorsal motor nucleus of the vagus (DMNX) and the medial subnucleus of the nucleus of the solitary tract (NTS), but not other subnuclei of the NTS, was significantly reduced by THC rostral to obex. At the level of the obex, THC reduced Fos expression in the area postrema and the dorsal subnucleus of the NTS. The highest density of CB1 receptor immunoreactivity was found in the DMNX and the medial subnucleus of the NTS. Lower densities were observed in the area postrema and dorsal subnucleus of the NTS. Caudal to obex, there was moderate density of staining in the commissural subnucleus of the NTS. These results show that THC selectively acts at CB1 receptors to reduce neuronal activation in response to emetic stimuli in specific regions of the dorsal vagal complex.

Animals↗