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Relationship between small intestinal fasting motility and vomiting in dogs.

Preceding vomiting, several changes in small intestinal motility have been described. They consist mainly of high-amplitude retrograde contractions and inhibition of motility before and after these contractions. The recordings of 94 episodes of emesis occurring spontaneously, during manometric studies of intestinal motility by means of infused catheters in dogs with gastric and duodenal cannulae, showed that 95.7% of all episodes developed during phase II of the migratory motor complex. In order to establish whether different phases of the fasting cyclic activity are associated with a different sensitivity to emetic stimulus, two agents, apomorphine, a centrally acting drug and copper sulfate, a peripherally acting agent, were administered at the beginning of phases I and II of the migratory motor complex. Coincident with spontaneously occurring vomiting, a statistically significative greater number of responses to both emetic agents was observed during phase II as compared to phase I. This finding suggests that cyclic changes of the small bowel motility are related to changes in the threshold of the vomiting center.

Animals↗

Chemical aversion conditioning in the treatment of alcoholism: further comments.

The literature on consummatory aversion (CA) conditioning in rats does provide a well-developed theoretical foundation for chemical aversion conditioning. Nevertheless, differences between rats and humans in CA learning suggest caution in extrapolating from the animal laboratory to the treatment of alcoholic patients. Serious methodological problems with studies of emetic therapy with alcoholics preclude unambiguous evaluation of its effects. Emetic therapy is an intrusive and relatively costly form of treatment which has not been shown to be more effective than alternative, less costly methods. The onus is on proponents of this method to demonstrate its specific advantages over alternative treatments.

Alcoholism↗

Involvement of dopamine D3 receptors in the area postrema in R(+)-7-OH-DPAT-induced emesis in the ferret.

We investigated the possible involvement of dopamine D3 receptors in R(+)-7-hydroxy-2-(N,N-di-n-propylamino)tetraline (R(+)-7-OH-DPAT)-induced emesis in the ferret. The R(+)enantiomer of 7-OH-DPAT (0.03-1 mg/kg, s.c.) caused emesis in a dose-dependent manner, whereas the S(-)enantiomer, even at 1 mg/kg s.c. failed to induce emesis. Quinpirole (0.1-1.0 mg/kg) and apomorphine (0.3 mg/kg, s.c. only) also elicited an emetic response. S(-)-Eticlopride, which has a high affinity for the dopamine D3 receptor, antagonized R(+)-7-OH-DPAT (0.3 mg/kg, s.c.)-induced emesis (ID50 1.4 micrograms/kg, s.c.). R(+)-7-OH-DPAT (0.1-1.0 microgram) administered into the 4th cerebral ventricle dose dependently induced emesis within 1 min of dosing in ferrets. Intracerebroventricularly administered S(-)-eticlopride (0.01-1 microgram) also inhibited the emesis induced by s.c. administration of R(+)-7-OH-DPAT. The emetic effect of R(+)-7-OH-DPAT was unaffected by abdominal vagotomy but was markedly reduced by ablation of the area postrema. These results suggest that dopamine D3 receptors in the area postrema play an important role in R(+)-7-OH-DPAT-induced emesis in the ferret.

Animals↗

The magical and medicinal usage of Stangeria eriopus in South Africa.

The underground caudex of the cycad Stangeria eriopus is used extensively by several ethnic groups in South Africa, mainly as an ingredient in magical potions but also as an emetic. An assessment of two main outlets showed that 3410 plants were sold in the month of July 1992; continued usage of this material now threatens the remaining plant populations. A proximate analysis of the caudex material gives high carbohydrate content with only small percentages of fat, protein, fibre and ash. An unusually high content of sodium sulphate may explain the efficacy of Stangeria-containing preparations as an emetic. The phytosterols sitosterol and stigmasterol are present in a 4:1 ratio while the fatty acid component comprises palmitic, oleic, stearic and arachidic acids. Twelve amino acids were identified in the material, including the non-protein amino acids beta-alanine, gamma-aminobutyric acid and pyroglutamic acid. The candidate neurotoxin beta-N-methylamino-L-alanine could not be detected but cycasin is present at the levels of 0.17% and 0.21% in fresh and dry caudex material, respectively and appears to be accompanied by the related toxin, macrozamin.

Attitude to Health↗

Abuse of drugs associated with eating disorders.

Concomitant bulimia nervosa and drug abuse are common in women. Drugs used by this group include diuretics, emetics, laxatives, and diet pills, as well as alcohol, cigarettes, and illicit street drugs. This paper applies principles from behavioral pharmacology to the problem of drug use by women with bulimia nervosa. The prevalence of use, primary effects, toxicity, detection, tolerance, withdrawal, and effects on appetite and weight are discussed for drugs used by bulimic women to reduce appetite or weight or to induce purging (e.g., diuretics, emetics, laxatives, and diet aids). Alternatives in the diagnosis and treatment of drug use in women with eating disorders are discussed.

Adult↗

Emesis induced by inhibitors of type IV cyclic nucleotide phosphodiesterase (PDE IV) in the ferret.

Emesis induced by inhibitors of type IV cyclic nucleotide phosphodiesterase (PDE IV) has been investigated in the ferret. The PDE IV inhibitors studied were: RS14203, R-rolipram and CT-2450 (i.e. (R)-N-[4-[1-(3-cyclopentyloxy-4-methoxyphenyl)-2-(4-pyridyl)ethyl]phenyl ]N'-ethylurea), in addition to the less active enantiomers S-rolipram and CT-3405. Following oral administrations, different emetic profiles were observed with time. Emesis induced by RS14203 exhibited a dose-response relationship but no such relationship was seen for R-rolipram or CT-2450. The incidence of emesis was positively influenced by the dose of PDE IV inhibitors administered, allowing a rank order of potency: RS14203 > R-rolipram > S-rolipram > CT-2450 > CT-3405. PDE IV inhibitor-induced emesis was abolished by the tachykinin NK1 receptor antagonist, CP-99,994. No peripheral release of substance P by PDE IV inhibitors seems to be involved in triggering the emetic reflex since L-743,310, which only has peripheral NK1 receptor antagonist activity, was without effect. The implication of 5-HT3 receptors in PDE IV inhibitor-induced emesis was variable. Our results suggest that the PDE IV inhibitors studied are mixed peripheral-central emetogens. PDE IV inhibition itself could be plausible mechanism of action of these agents. However, whether emesis is mediated via a specific isoform of PDE IV remains to be established.

Animals↗

Death following cupric sulfate emesis.

CASE HISTORY: A 25-year-old woman who had ingested about 20 tablets of diazepam 2.5 mg in a suicide attempt was given cupric sulfate 2.5 g in 1750 mL water as an emetic, but died 3 days later. On autopsy, death was attributed to acute hemolysis and acute renal failure due to copper poisoning. Copper concentrations were 5.31 microg/mL in whole blood, 19.0 microg/g in the liver, 8.9 microg/g in the kidney, 1.1 microg/L in the brain, 1.1 microg/g in the gastric wall, 1.5 microg/g in the jejunal wall, 0.3 microg/g in the colon wall, 4.6 microg/g in the gastric contents, and 12.6 microg/g in the intestinal contents (fresh weight). This case and 10 others from the Chinese medical literature provide additional evidence that cupric sulfate is a corrosive poison and contraindicated as an emetic.

Adult↗

Conditioned taste aversion and c-fos expression in the rat brainstem after administration of various USs.

Conditioned taste aversion (CTA) is a form of association learning established when an animal associates a conditioned stimulus (taste) with a subsequent unconditioned stimulus (US, illness). We have studied the relationship between the efficacy of inducing CTA to 0.1% saccharin and c-fos expression in the lower brain stem following administration of 13 different USs in rats. The effective USs were grouped into abdominal irritants, rewarding drugs and emetic agents. Regardless of the properties of USs, good correlation was detected between the strength of CTA and c-fos expression within the area postrema, caudal and intermediate subdivisions of nucleus tractus solitarius and the external lateral subnucleus of the parabrachial nucleus. Only hypertonic saline was exceptional because of the experimental procedure: it induced strong c-fos expression, but was not an effective US for CTA formation. Different dosages of the emetic LiCl induced CTA and c-fos expression in a dose-dependent manner.

Animals↗

A study of tolerance to apomorphine.

1. The present study was designed to investigate tolerance to several pharmacological effects of apomorphine. 2. Changes in blood pressure, heart rate, plasma noradrenaline levels, rectal temperature, respiratory rate and retching plus vomiting were compared after administration of apomorphine (200 micrograms kg-1, i.v. as a bolus) or saline at different time intervals (30, 120 and 720 min) in four groups of chloralose-anaesthetized dogs. 3. The first administration of apomorphine induced a significant decrease in blood pressure and rectal temperature, a marked rise in heart rate with no change in noradrenaline plasma levels or respiratory rate. Emesis occurred in 71% of the animals. 4. A second administration of apomorphine 30 min later failed to modify blood pressure or heart rate. In contrast, the magnitude of apomorphine-induced changes in blood pressure and heart rate was similar to that observed after the first administration when apomorphine was given 120 or 720 min later. 5. The apomorphine-induced decrease in rectal temperature evoked by a second dose of apomorphine was less marked when given 30 and 120 min after the first dose and unchanged when given 720 min later. 6. The number of animals exhibiting retching and vomiting was lower when apomorphine was reinjected after 30 min than when the time between two successive injections of apomorphine was 120 or 720 min. 7. These results show that tolerance to apomorphine involves its cardiovascular, hypothermic and emetic effects. The time course of tolerance to repeated injections of apomorphine is longer for its hypothermic than for its hypotensive or emetic effects. This suggests a tissue-specific regulation of D2 dopamine receptors to repeated injections of apomorphine.

Animals↗

Skin reactivity of unsensitized monkeys upon challenge with staphylococcal enterotoxin B: a new approach for investigating the site of toxin action.

The correlation between skin tests and emetic responses in unsensitized monkeys was used to elucidate the cellular site of action of staphylococcal enterotoxin B (SEB). Evidence is presented that SEB administered intradermally provoked immediate-type skin reactions associated with mild degranulation of cutaneous mast cells. The cytoplasma showed signs of synthetic and metabolic activity, with formation of vesicles and increased prominence of mitochondria. Carboxymethylation of histidine residues of SEB altered the molecule (cSEB) from more alkaline components to more acidic species with increased microheterogeneity. This modification caused a loss in toxicity and completely abrogated the skin-sensitizing activity without changing the immunological specificity. cSEB, however, could compete with SEB for binding sites on the target cell surface. Previously, compound 48/80-treated skin sites behaved refractively to challenge with SEB, indicating that mediators from cutaneous mast cells are required for SEB-induced skin reactions. Skin reactions as well as emetic responses challenged with SEB were completely inhibited by H2 receptor antagonists and calcium channel blockers but not by H1 antihistamine or competitive antagonists of serotonin. This new approach provides a model for investigating the mechanisms of SEB action.

Animals↗

Identification of a fourth staphylococcal enterotoxin, enterotoxin D.

A fourth staphylococcal enterotoxin was identified serologically with antiserum to the very crude enterotoxic products of growth of a strain which also produces enterotoxin C, and then with antiserum to the considerably purified enterotoxic antigen of a strain which produces only the new enterotoxin. The identification of this antigen as enterotoxin D was based on the following observations. It was produced by strains which do not produce enterotoxins A, B, or C; it was absent in the growth products of nonenterotoxigenic strains; when appreciably purified, it was associated with emetic activity in the cat, and its biological activity was neutralized only by antisera containing its specific antibody and not by antibodies to enterotoxins A, B, and C. Staphylococcal strain 494 (ATCC 23235) was selected as the prototype strain. The production of this enterotoxin alone and together with enterotoxin A by strains of food-poisoning origin indicates that its role in food poisoning is second in frequency only to that of enterotoxin A. The incidence of production of enterotoxins A, B, C, and D, and of unidentified cat emetic substances by strains from several source categories, is presented.

Animals↗

Canine salivary secretion from the submaxillary glands before and during retching.

To investigate the changes in salivary secretion associated with emesis, salivary secretion from the submaxillary gland and centrifugal discharge from the parasympathetic postganglionic nerve fibers from the submandibular ganglion were measured after emetic stimulation in chloralose-anesthetized and paralyzed dogs. In the basal condition, saliva flow and the basal frequencies of single unit discharges from the parasympathetic nerve were very low. Esophageal and gastric distension and lingual nerve afferent stimulation generally increased salivary secretion and nerve activity. Administration of apomorphine (0.2-0.3 mg/kg im) or intragastric infusion of copper sulfate (10%, 50 ml) elicited an excitation of parasympathetic nerve activity, and salivary secretion was facilitated in parallel to this nerve activity. The excitatory responses induced by emetic stimulation were suddenly depressed in correspondence with retching activities. This depression in nerve activity appeared 200-400 ms after the beginning of retching volleys of the phrenic nerve and continued during retching. These results indicate that the salivary center receives excitatory and inhibitory inputs from two different sources before and during retching activities, respectively.

Animals↗

Vomiting induction by ipecac syrup in dogs and ferrets.

The dog has been used as an experimental animal in emesis research. In this study, we analyzed the emetic effects of ipecac syrup using a smaller animal, the ferret, and compared its response to that of the dog. Dogs and ferrets were divided into 4 groups (n = 4, each). Each group was given either 0.1, 0.25, 0.5, or 1.0 ml/kg of ipecac syrup, and the latency and numbers of retching and vomiting were recorded. Animals given an equal volume of saline served as controls. The numbers of vomiting and retching increased dose-dependently in both dogs and ferrets, and there was no difference in latency and numbers of vomiting between them. The numbers of retching were greater in ferrets than in dogs at > or = 0.25 ml/kg. Taking these results into consideration, the ferret seems to be as useful as the dog in studies on emetic effects of ipecac syrup.

Animals↗

Cardiovascular collapse and propranolol overdose.

We report three cases of propranolol overdose in two patients, both of whom suffered cardiovascular collapse after receiving an emetic compound in a hospital's casualty department. Such a collapse may be caused by vagal activity in the presence of sympathetic beta-blockade. We recommend the administration of atropine, which may increase vagal tone, before a patient receives an emetic compound, or undergoes gastric lavage or endotracheal intubation.

Adolescent↗

Emesis, radiation exposure, and local cerebral blood flow in the ferret.

We examined the sensitivity of the ferret to emetic stimuli and the effect of radiation exposure near the time of emesis on local cerebral blood flow. Ferrets vomited following the administration of either apomorphine (approx 45% of the ferrets tested) or peptide YY (approx 36% of those tested). Exposure to radiation was a very potent emetic stimulus, but vomiting could be prevented by restraint of the hindquarters of the ferret. Local cerebral blood flow was measured using a quantitative autoradiographic technique and with the exception of several regions in the telencephalon and cerebellum, local cerebral blood flow in the ferret was similar to that in the rat. In animals with whole-body exposure to moderate levels of radiation (4 Gy of 137Cs), mean arterial blood pressure was similar to that in the control group. However, 15-25 min following irradiation there was a general reduction of local cerebral blood flow ranging from 7 to 33% of that in control animals. These cerebral blood flow changes likely correspond to a reduced activation of the central nervous system.

Animals↗

Fecal and oral shedding of Helicobacter pylori from healthy infected adults.

CONTEXT: Helicobacter pylori commonly infects humans; however, its mode of transmission remains unknown. OBJECTIVE: To determine how humans-the primary host for H pylori-shed the organism into the environment. DESIGN: Controlled clinical experimental study conducted from February through December 1998. SETTING: Clinical research unit of a hospital in northern California. PATIENTS: Sixteen asymptomatic H pylori-infected and 10 uninfected adults. INTERVENTION: A cathartic (sodium phosphate) and an emetic (ipecac) were given to all infected subjects and an emetic was given to 1 uninfected subject. MAIN OUTCOME MEASURE: Confirmed H pylori isolates cultured from stool, air, or saliva before and after catharsis and emesis and from vomitus during emesis. Isolates were fingerprinted using repetitive extragenic palindromic (REP) polymerase chain reaction and species identity was confirmed by sequencing the 16s ribosomal RNA gene. RESULTS: All vomitus samples from infected subjects grew H pylori, often in high quantities. Air sampled during vomiting grew H pylori from 6 (37.5%) of the 16 subjects. Saliva before and after emesis grew low quantities of H pylori in 3 (18.8%) and 9 (56.3%) subjects, respectively. No normal stools and only 22 (21.8%) of 101 induced stools grew the organism, although 7 (50.0%) of 14 subjects had at least 1 positive culture (2 stool culture samples were contaminated by fungus and were not included). Fingerprints of isolates within subjects were identical to one another but differed among subjects. No samples from uninfected subjects yielded H pylori. CONCLUSIONS: Helicobacter pylori can be cultivated uniformly from vomitus and, occasionally, from saliva and cathartic stools. The organism is potentially transmissible during episodes of gastrointestinal tract illness, particularly with vomiting.

Adult↗

Ultrastructure of the feline area postrema.

The morphology of the feline area posterma (AP), a circumventricular organ, has been studied by scanning (SEM) and transmission electron microscopy (TEM). In SEM preparations the boundary of the AP was sharply delineated by the absence of kinocilia. Microvilli were numerous and seemed to be concentrated at the junction between ependymal cells, imparting a polygonal surface pattern superimposed on cell boundaries. Some cell processes were present on the AP surface, but no supra-ependymal cell bodies could be seen over the AP proper. In TEM preparations the AP was characterized by blood vessels with distinct perivascular spaces. These spaces contained fibroblasts and collagen, and were limited by basal laminae. Capillary endothelial cells were typically fenestrated and contained numerous pinocytotic vesicles. Bulbous ending of attenuated cellular processes terminated on the external basal laminae of AP vasculture. Some of these endings could be traced to the cells covering the ventricular surface of the AP. These cells demonstrated several features co-mon to ependymal cells which have been identified as tanycytes. The presence of small neurons frequently seen in groups of three or four confirm previous light microscopic studies. Synapses predominantly of the axodendritic variety were observed, and both dense cored and clear cored vesicles were present on the same ending. Myelinated and unmyelinated axons were a consistent finding in the AP with the former being more abundant in the lateral margins of the AP and in the region of the area subpostrema. The chemoreceptive function of the AP has been widely accepted; however, studies indicate that it is not possible to distinguish species possessing an emetic reflex on the basis of ultrastructural morphology. The possibility that the AP serves functions in addition to emetic chemoreception is considered.

Animals↗

Liver disease in Egypt: hepatitis C superseded schistosomiasis as a result of iatrogenic and biological factors.

In Egypt, schistosomiasis was traditionally the most important public health problem and infection with Schistosoma mansoni the major cause of liver disease. From the 1950s until the 1980s, the Egyptian Ministry of Health (MOH) undertook large control campaigns using intravenous tartar emetic, the standard treatment for schistosomiasis, as community-wide therapy. This commendable effort to control a major health problem unfortunately established a very large reservoir of hepatitis C virus (HCV) in the country. By the mid-1980s, the effective oral drug, praziquantel, replaced tartar emetic a s treatment f o r schistosomiasis in the entire country. This both reduced schistosomal transmission and disease and interrupted the "occult" HCV epidemic. It was evident when diagnostic serology became available in the 1990s that HCV had replaced schistosomiasis as the predominant cause of chronic liver disease. Epidemiological studies reported a high prevalence and incidence of HCV, particutarly within families in rural areas endemic for schistosomiasis. Clinical studies showed 70% to 90% of patients with chronic hepatitis, cirrhosis, or hepatocellular carcinoma had HCV infections. Co-infections with schistosomiasis caused more severe liver disease than infection with HCV alone. Schistosomiasis was reported to cause an imbalance in HCV-specific T-cell responses leading to increased viral load, a higher probability of HCV chronicity, and more rapid progression of complications in co-infected persons. As complications of HCV usually occur after 20 years of infection, the peak impact of the Egyptian outbreak has not yet occurred. Efforts have been initiated by the Egyptian MOH to prevent new infections and complications of HCV in the estimated 6 million infected persons.

Egypt↗