pica and Vomiting

We review information about the potential mechanisms underlying nausea and vomiting in pregnancy (NVP), food cravings, and/or aversions in pregnancy. In addition to providing overviews about genetic predispositions and hormonal associations with appetite sensations and NVP, we review two functional explanations: the "maternal and embryo protection" and the "placental growth and development" hypotheses. We conclude with a discussion about the kinds of data that would enable us to better evaluate the relative advantages and disadvantages of NVP across disparate resource and ecological conditions.

Topics: Adaptation, Physiological; Appetite; Cultural Deprivation; Feeding and Eating Disorders; Female; Food Preferences; Humans; Maternal Nutritional Physiological Phenomena; Models, Biological; Nausea; Pica; Pregnancy; Pregnancy Complications; Vomiting

Women all over the globe report physical and appetite sensations in early pregnancy, and this study contributes to this growing literature by reporting on the appetite sensations experienced by pregnant women from rural Tanzania. Appetite changes associated with 545 pregnancies were compiled from surveys conducted to report on the prevalence of appetite loss, nausea, vomiting, dizziness, joint pain, cravings, aversions, and pica experienced by agropastoral women from rural north-central Tanzania. In addition to these symptoms, specific craved and aversive food groups are described. Statistical associations among appetite sensations, NVP, and birthweight are tested. The only symptom associated with a lower average birth weight for newborns was vomiting. In addition to investigating micronutrient content and chemical properties of specific food and non-food items, future research should include assessing relationships among various appetite sensations and short- and long-term health outcomes for both the mother and child.

Topics: Adult; Appetite; Birth Weight; Cross-Sectional Studies; Female; Food Preferences; Humans; Infant, Low Birth Weight; Infant, Newborn; Morning Sickness; Nausea; Pica; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prevalence; Rural Population; Tanzania; Vomiting

Nutrition assessment and counseling are integral components of preconception and prenatal care. The average-size woman should gain between 11.25 and 15.75 kg (25 and 35 lb) during a normal pregnancy. Some factors identify the pregnant woman with a nutrition risk. Vitamin and mineral supplementation should be based on a dietary assessment. Common discomforts of pregnancy frequently can be managed with dietary modification and safe pharmacotherapeutics. The coordinated efforts of health care providers, registered dietitians, the Women, Infants, and Children (WIC) nutrition program, local health departments and Cooperative Extension Service offices can provide appropriate nutrition assessment, education and intervention.

Topics: Caffeine; Constipation; Female; Humans; Lactose Intolerance; Nausea; Nutrition Assessment; Nutritional Physiological Phenomena; Pica; Pregnancy; Pregnancy Complications; Sodium, Dietary; Substance-Related Disorders; Vomiting; Weight Gain

Bulimarexia, an eating disorder that is characterized by binge eating followed by self-induced vomiting or abuse of cathartic or diuretic drugs, has been defined as both a sequela of anorexia nervosa and a distinct eating disorder. In this review the presentation, prevalence, and complications of the various eating disorders--anorexia nervosa, pica, rumination disorder of infancy, and bulimia/bulimarexia--are discussed. Detailed attention is given to the potential medical hazards of bulimarexia. These hazards may be categorized according to the organ system affected or the individual behavioral components of bulimarexia. Because bulimarexia is commonly practiced in secrecy, its presentation may be in the form of one of its medical complications. Therefore, physicians must know the behavioral components of bulimarexia and its potential medical hazards. Optimal care of these patients requires collaborative efforts from a physician and behavioral therapist.

Topics: Adolescent; Adult; Anorexia Nervosa; Cathartics; Diuretics; Feeding and Eating Disorders; Female; Gastroesophageal Reflux; Humans; Hyperphagia; Infant; Male; Nutrition Disorders; Pica; Substance-Related Disorders; Vomiting

As a traditional Chinese anti-emetic formula, Xiao-Ban-Xia decoction (XBXD) was recorded in Golden Chamber, and has promising anti-emetic effect on chemotherapy-induced nausea and vomiting (CINV).. This study aimed to determine whether the underlying mechanism of XBXD against CINV is correlated to the restoration of cisplatin-induced PINK1/Parkin mediated mitophagy deficiency and mitigation of gastrointestinal inflammation.. The rat pica model was established by intraperitoneal injection of cisplatin 6 mg/kg. The daily kaolin consumption, food intake and body weight were recorded every 24 h. The pathological damage of gastric antrum and ileum were observed by hematoxylin-eosin staining. The levels of serum reactive oxygen species (ROS), interleukin-1β (IL-1β) and interleukin-1β (IL-18) were detected by ELISA. The expression of microtubule-associated protein 1 light chain 3 (LC3) in gastric antrum and ileum was detected by Immunofluorescence staining. The levels of LC3II, P62/SQSTM1, PTEN-induced putative protein kinases (PINK1), E3 ubiquitin ligase (Parkin), AMP-dependent protein kinases (AMPK), phosphorylated AMPK (p-AMPK), nuclear factor erythroid 2-related factor (Nrf2) and kelch like ECH Associated Protein 1 (Keap1) in gastric antrum and ileum were assayed by western blotting.. At 24 h and 72 h following cisplatin challenge, XBXD inhibited cisplatin-induced elevation of kaolin consumption, and improved the daily food intake and body weight loss in rats. Cisplatin-induced gastrointestinal histopathological damages were alleviated, and serum levels of ROS, IL-1β and IL-18 increases were mitigated following XBXD treatments. In gastric antrum and ileum, XBXD activated AMPK-Nrf2 signaling pathway and restored cisplatin-induced PINK1/Parkin mediated mitophagy deficiency.. XBXD significantly ameliorated CINV in a cisplatin-induced rat pica model. The underlying anti-emetic mechanism of XBXD might be related to the activation of AMPK-Nrf2 signaling pathway and the restoration of cisplatin-induced PINK1/Parkin-mediated mitophagy deficiency in the gastrointestinal tract.

Topics: AMP-Activated Protein Kinases; Animals; Antiemetics; Cisplatin; Interleukin-18; Interleukin-1beta; Kaolin; Kelch-Like ECH-Associated Protein 1; Mitophagy; NF-E2-Related Factor 2; Pica; Pinellia; Rats; Reactive Oxygen Species; Ubiquitin-Protein Ligases; Vomiting

Xiaobanxia Decoction (XBXD), a traditional antiemetic formula, is effective in preventing chemotherapy-induced nausea and vomiting (CINV), but its underlying mechanism has not been fully clarified.. To investigate whether the antiemetic mechanisms of XBXD against CINV is associated with the reduction of GSDME-mediated pyroptosis and the alleviation of gastrointestinal inflammation induced by cisplatin.. We established the in vivo pica rat model and the in vitro small intestinal epithelial cell (IEC-6 cell) injury model by cisplatin challenge. The levels of ROS, IL-1β, IL-18, HMGB1 were measured by ELISA. The histopathological changes of gastrointestinal (GI) tissues were examined by HE staining. The expression and localization of GSDME in GI tissues were determined by IHC. The GSDME mRNA expression in GI tissues was determined by RT-PCR. The IEC-6 cell viability was detected by CCK-8. The morphology of IEC-6 cells was observed by optical microscope and scanning electron microscopy. Pyroptosis was examined using Hoechst33342/PI staining. The intracellular ROS levels were measured with the fluorescent probe DCFH-DA. The expression levels of JNK, p-JNK, Bax, Bcl-2, caspase-9, caspase-3 and GSDME in GI tissues and IEC-6 cells were determined by WB.. We found that the cumulative kaolin intake (pica behavior, analogous to emesis) significantly increased in cisplatin-treated rats, accompanied by significant inflammatory pathological changes of GI tissues. XBXD decreased the cumulative kaolin intake and alleviated GI inflammation in cisplatin-treated rats by inhibiting the activation of the ROS/JNK/Bax signaling pathway and by reducing GSDME-mediated pyroptosis. Additionally, cisplatin damaged IEC-6 cells by activating GSDME-dependent pyroptosis. XBXD reduced GSDME-mediated IEC-6 cell pyroptotic death by regulating the ROS/JNK/Bax signaling pathway.. This study suggested that GSDME-mediated pyroptosis greatly contributes to the occurrence of CINV, and suppressing GSDME-mediated pyroptosis is the important antiemetic mechanism of XBXD.

Topics: Animals; Antiemetics; Antineoplastic Agents; bcl-2-Associated X Protein; Caspase 3; Cisplatin; Inflammation; Kaolin; Nausea; Pica; Pyroptosis; Rats; Reactive Oxygen Species; Vomiting

Nausea and vomiting are common gastrointestinal side effects of oxaliplatin chemotherapy used for the treatment of colorectal cancer. However, the mechanism underlying oxaliplatin-induced nausea and vomiting is unknown. The stomach is involved in the emetic reflex but no study investigated the effects of oxaliplatin treatment on the stomach. In this study, the in vivo effects of oxaliplatin treatment on eating behaviour, stomach content, intrinsic gastric neuronal population, extrinsic innervation to the stomach, levels of mucosal serotonin (5-hydroxytryptamine, 5-HT), and parasympathetic vagal efferent nerve activity were analysed. Chronic systemic oxaliplatin treatment in mice resulted in pica, indicated by increased kaolin consumption and a reduction in body weight. Oxaliplatin treatment significantly increased the stomach weight and content. The total number of myenteric and nitric oxide synthase-immunoreactive neurons as well as the density of sympathetic, parasympathetic, and sensory fibres in the stomach were decreased significantly with oxaliplatin treatment. Oxaliplatin treatment significantly increased the levels in mucosal 5-HT and the number of enterochromaffin-like cells. Chronic oxaliplatin treatment also caused a significant increase in the vagal efferent nerve activity. The findings of this study indicate that oxaliplatin exposure has adverse effects on multiple components of gastric innervation, which could be responsible for pica and gastric dysmotility.

Topics: Animals; Mice; Nausea; Oxaliplatin; Pica; Serotonin; Stomach; Vomiting

Donepezil, an acetylcholinesterase inhibitor, is associated with gastrointestinal symptoms, such as nausea, vomiting, and anorexia, which may affect adherence to continuous therapy. Since Rikkunshi-To, a Japanese herbal medicine, activates the ghrelin signaling pathway and promotes gastrointestinal function, it is administered to prevent gastrointestinal symptoms. We herein investigated whether donepezil-induced gastrointestinal side effects in mice are ameliorated by Rikkunshi-To and if its therapeutic efficacy is mediated by ghrelin. Since pica behavior, the ingestion of kaolin, correlates with nausea and vomiting in humans, donepezil was intraperitoneally administered with or without Rikkunshi-To daily to mice, and food and kaolin intakes were monitored. The effects of donepezil on intestinal motility and a ghrelin receptor antagonist on donepezil-induced pica behavior, anorexia, and changes in intestinal motility were examined in mice treated with Rikkunshi-To. Pica behavior and anorexia were significantly induced by donepezil and significantly inhibited by Rikkunshi-To. Intestinal motility was significantly suppressed by donepezil and promoted by Rikkunshi-To. Furthermore, the therapeutic effects of Rikkunshi-To were antagonized by the ghrelin receptor antagonist. The present results support the therapeutic efficacy of Rikkunshi-To against donepezil-induced gastrointestinal side effects.

Topics: Acetylcholinesterase; Animals; Anorexia; Donepezil; Drugs, Chinese Herbal; Ghrelin; Humans; Kaolin; Medicine, Kampo; Mice; Nausea; Pica; Receptors, Ghrelin; Vomiting

Studies show that traditional Chinese medicine (TCM), such as Liujunanwei (LJAW) decoction, can play important roles in alleviating side effects of chemotherapy. The purpose of this study was to understand how LJAW can counter chemotherapy-induced emesis

Topics: Animals; Antineoplastic Agents; Cisplatin; Kaolin; Nausea; Pica; Rats; RNA, Ribosomal, 16S; Vomiting

During pregnancy, women tend to improve their lifestyle habits and refine their dietary intake. Quite often, however, these dietary improvements take an unhealthy turn, with orthorexia nervosa (ON) practices being apparent. The aim of the present pilot cross-sectional study was to assess the prevalence of ON tendencies and the incidence of pica and record diet practices in a sample of pregnant women. A total of 157 pregnant women were recruited through private practice gynecologists during the first months of 2021. Nutrition-related practices were recorded, orthorexic tendencies were assessed using the translated and culturally adapted Greek version of the ORTO-15 questionnaire, pica practices were evaluated with a binary question and nausea and emesis during pregnancy (NVP) was evaluated using the translated modified Pregnancy-Unique Quantification of Emesis and Nausea (mPUQE). Only two women reported pica tendencies, with ice and snow being the consumed items. The majority (61.1%) of women reported improving their diet since conception was achieved. Folic acid and iron oral nutrient supplements (ONS) were reportedly consumed by the majority of participants (87.9% and 72.6%, respectively) and 9.6% reported using herbal medicine products. The ORTO-15 score was reduced with tertiary education attainment, ART conception, being in the third trimester of pregnancy, consumption of folic acid and MV supplements and was only increased among women who were at their first pregnancy. The majority of participants experienced severe NVP and the remaining experienced moderate NVP. NVP was associated with lower hemoglobin levels, lack of supplementary iron intake, avoidance of gluten-containing foods, as well as with increased gestational weight gain. The results highlight the need to screen pregnant women for disturbed eating behaviors and nutrition-related problems, in order to ensure a healthy pregnancy outcome.

Topics: Cross-Sectional Studies; Female; Folic Acid; Humans; Iron; Morning Sickness; Nausea; Pica; Pilot Projects; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnant Women; Vomiting

Trichobezoars are rare, but most commonly found in young women with trichophagia and trichotillomania. Complications can include iron deficiency anaemia and gastric erosion or, rarely, perforation. A 19-year-old woman presented with epigastric pain, vomiting and lethargy. Initial investigations revealed a palpable abdominal fullness on examination and iron deficiency anaemia. Oesophagogastroduodenoscopy found a large trichobezoar associated with gastric erosions, polyps and an ulcer. Subsequently, the patient reported previous consumption of artificial hair extensions, which ceased 5 years previously. Attempts to remove the trichobezoar by endoscopy were ineffective and in line with current literature, laparotomy was successful. This case describes a rare cause of trichobezoar and emphasises the importance of appropriate initial investigations and definitive management.

Topics: Abdominal Pain; Bezoars; Endoscopy; Female; Hair; Humans; Laparotomy; Pica; Vomiting; Young Adult

Topics: Abdominal Pain; Adult; Anemia, Iron-Deficiency; Depressive Disorder; Diagnosis, Differential; Female; Hemoglobins; Humans; Lead; Lead Poisoning; Menorrhagia; Pica; Vomiting

Topics: Bezoars; Child, Preschool; Diarrhea; Female; Gastroscopy; Humans; Intestinal Obstruction; Intestines; Pica; Stomach; Syndrome; Vomiting

The cytotoxic drugs used in chemotherapy are often accompanied by nausea and vomiting. Despite the use of antiemetic drugs, chemotherapy-induced nausea and vomiting (CINV) remain significant side effects for cancer patients and are associated with serotonin type 3 receptor (5-HT

Topics: Animals; Antiemetics; Antineoplastic Agents; Appetite; Cisplatin; Farnesol; Male; Nausea; Oils, Volatile; Pica; Rats; Rats, Wistar; Receptors, Serotonin, 5-HT3; Sesquiterpenes; Vomiting; Weight Loss

Topics: Adult; Female; Humans; Nausea; Pain; Pica; Soaps; Vomiting

The aim of this study was to characterize pica behavior in cats.. Cat owners were recruited to participate in a questionnaire survey on pica behavior exhibited by their cats. Emphasis was put on the type of item ingested. Questions on early history and environment, as well as general health and gastrointestinal signs, were asked. Owners of healthy cats not showing pica were also recruited into a control group. Associations between variables and groups were statistically tested.. Pica was directed most commonly at shoelaces or threads, followed by plastic, fabric, other items, rubber, paper or cardboard and wood. Some cats ingested specific items but only chewed others. A significant positive association was found between sucking and ingesting fabric (P = 0.002). Ad libitum feeding was significantly lower in the pica group than the control group (P = 0.01). Prevalence of self-sucking behavior was significantly higher in the pica group than the control group (P = 0.001). Cats with pica vomited significantly more often than control cats (P = 0.01).. Pica, the ingestion of inedible items, does not seem to be the consequence of a suboptimal environment or early weaning. Cats with pica were less commonly fed ad libitum than healthy cats. As frequently reported, pica and vomiting were related, but the causative association is not well established and thus warrants further investigation.

Topics: Animals; Behavior, Animal; Cat Diseases; Cats; Female; Male; Mastication; Pets; Pica; Surveys and Questionnaires; Vomiting

The ability to assess the potential for gastrointestinal adverse events in a preclinical setting is a challenge in the development of new drugs, as the vast majority of in vivo research is conducted in rodent species lacking a vomiting reflex. The use of higher species capable of emesis is often limited by cost, technical experience, and relevant efficacy models to define a therapeutic index. Additionally, investigators should be mindful of ethical considerations when using more sentient species when an alternative in lower species is available. This unit describes the use of pica behavior in rodents as an alternative for evaluating emetic potential in vivo. After an acclimation period, the incidence of rats engaging in pica following the administration of a test article can be used to generate a dose-response curve of the pica behavior. When linked with an appropriate efficacy model, this allows compounds to be ranked based on therapeutic index. © 2016 by John Wiley & Sons, Inc.

Topics: Animals; Behavior, Animal; Drug Evaluation, Preclinical; Eating; Feeding Behavior; Gastrointestinal Contents; Models, Animal; Pica; Rats; Vomiting

We investigated the effects of olanzapine on cisplatin-induced pica (the consumption of non-nutrient materials such as kaolin) and glucose homeostasis in rats to clarify the effects of olanzapine when used as an anti-emetic drug. Rats were injected intraperitoneally (i.p.) with either 5 mg/kg cisplatin or saline. Additionally, 2 or 10 mg/kg olanzapine were administered i.p. to the rats 10 min before the administration of cisplatin and subsequently administered every 24 h for 3 d. Kaolin and food intake was measured using an automatic monitoring apparatus. Plasma glucose levels were measured by an enzyme electrode method. The plasma levels of insulin and intact proinsulin were measured by enzyme-linked immunosorbent assay (ELISA). The proinsulin-to-insulin (P/I) ratio was calculated. Cisplatin significantly increased kaolin intake, but decreased food intake and body weight up to 72 h. Olanzapine had no effect on these parameters. Neither olanzapine nor cisplatin alone had a significant effect on the plasma levels of glucose, insulin, or proinsulin. However, a combination of olanzapine and cisplatin significantly decreased plasma insulin levels, but increased plasma intact proinsulin levels and the P/I ratio. Our results suggest that an additive deterioration of insulin-secreting beta-cell function and disturbance of glucose homeostasis should be considered during treatment of patients with olanzapine for cisplatin-induced nausea and vomiting.

Topics: Animals; Antiemetics; Antineoplastic Agents; Benzodiazepines; Blood Glucose; Cisplatin; Eating; Homeostasis; Kaolin; Male; Nausea; Olanzapine; Pica; Proinsulin; Rats, Wistar; Vomiting

Although the acute toxic effects of trichothecene mycotoxin deoxynivalenol (DON or vomitoxin), a known cause of human food poisoning, have been well characterized in several animal species, much less is known about closely related 8-ketotrichothecenes that similarly occur in cereal grains colonized by toxigenic fusaria. To address this, we compared potencies of DON, 15-acetyldeoxynivalenol (15-ADON), 3-acetyldeoxynivalenol (3-ADON), fusarenon X (FX), and nivalenol (NIV) in the mink emesis model following intraperitoneal (ip) and oral administration. All five congeners dose-dependently induced emesis by both administration methods. With increasing doses, there were marked decreases in latency to emesis with corresponding increases in emesis duration and number of emetic events. The effective doses resulting in emetic events in 50% of the animals for ip exposure to DON, 15-ADON, 3-ADON, FX, and NIV were 80, 170, 180, 70, and 60 µg/kg bw, respectively, and for oral exposure, they were 30, 40, 290, 30, and 250 µg/kg bw, respectively. The emetic potency of DON determined here was comparable to that reported in analogous studies conducted in pigs and dogs, suggesting that the mink is a suitable small animal model for investigating acute trichothecene toxicity. The use of a mouse pica model, based on the consumption of kaolin, was also evaluated as a possible surrogate for studying emesis but was found unsuitable. From a public health perspective, comparative emetic potency data derived from small animal models such as the mink should be useful for establishing toxic equivalency factors for DON and other trichothecenes.

Topics: Administration, Oral; Animals; Dose-Response Relationship, Drug; Female; Injections, Intraperitoneal; Male; Mice; Mink; Mycotoxins; Pica; Toxicity Tests; Trichothecenes; Vomiting

Panax ginseng is an indigenous medicinal herb and has traditionally been used among Asian population for relief of many human ailments. We investigated the prophylactic role of Korean P. ginseng extract (KG) against X-ray irradiation-induced emesis in an acute rat pica model. Rats were treated with KG (12.5, 25, 50 mg/kg orally at -48, -24 and 0 h) prior to X-ray irradiation (6 Gy), and intake of kaolin and normal food and body weight changes examined as an index of the acute emetic stimulus. Levels of serotonin in small intestine tissue were assessed and histopathology of gastric tissue, small intestine and colon examined specific staining. Pre-treatment with KG (12.5 and 25 mg/kg) reduced X-ray irradiation-induced kaolin intake at 24h. Normal food intake was improved in rats treated with 25 mg/kg KG. The anti-emetic effect of KG was further confirmed on the basis of serotonin release, histopathological findings. Our findings collectively indicate that KG protects against X-ray irradiation-induced acute pica to a moderate extent, leading to improved feeding behavior in rats.

Topics: Animals; Body Weight; Colon; Energy Intake; Feeding Behavior; Ginsenosides; Intestine, Small; Kaolin; Male; Panax; Phytotherapy; Pica; Plant Extracts; Rats; Rats, Sprague-Dawley; Serotonin; Stomach; Vomiting; X-Rays

In the present study, we investigate the effect of Korean ginseng root extract (KG) on cisplatin-induced pica in a rat model. Rats were treated with KG before (25, 50, and 100 mg/kg) or after (12.5, 25, and 50 mg/kg) a single intraperitoneal injection of cisplatin (7 and 6 mg/kg, respectively). We examined intake of kaolin and normal food as an indicator of the emetic stimulus every 24 h for 120 h. Changes in body weight, haematology and histopathology were additionally assessed. Pre-treatment with KG (25 and 50 mg/kg) significantly attenuated cisplatin-induced kaolin intake (24, 48, and 72 h) and markedly improved intake of normal food by rats at 48, 72, 96, and 120 h. Cisplatin-induced kaolin intake was markedly decreased upon post-treatment of rats with KG (12.5, 25, and 50 mg/kg) at 24 h. Notably, post-treatment with the lowest KG dose resulted in a significant anti-pica effect and improved food intake until 72 h. The magnitude of body weight reduction was significantly diminished in rats pre-treated/post-treated with 25, 50, and 12.5 mg/kg KG. The anti-pica effects of KG were further confirmed with haematological and histopathological findings. Our findings collectively indicate that KG improves the resistance of rats against emesis.

Topics: Animals; Anorexia; Antineoplastic Agents; Body Weight; Chromatography, High Pressure Liquid; Cisplatin; Disease Models, Animal; Dose-Response Relationship, Drug; Male; Panax; Pica; Plant Extracts; Plant Roots; Rats; Rats, Sprague-Dawley; Vomiting

Oxycodone, a semisynthetic opioid analgesic, is frequently prescribed for the management of pain. Side effects of nausea and emesis affect patient compliance and limit its therapeutic use. The present study established that an antinociceptive dose of oxycodone (15 mg/kg; oral) induces the pica response. We found sex differences in the temporal course of pica, with females having a longer duration. Opioid receptors mediated the pica response, as 1.0 mg/kg naloxone transiently attenuated and 2.0 mg/kg naloxone blocked pica. A κ-selective antagonist failed to block the response, suggesting mediation by μ opioid receptor. For further validation, we used the well established kaolin intake model to assess pica with the chemotherapeutic drug cisplatin as a positive control. Oxycodone and cisplatin significantly increased kaolin intake 4- to 7-fold, and the wet weight of stomach was elevated 2- to 3-fold. To examine the underlying neural circuitry, we investigated c-fos activation in the area postrema and nucleus of solitary tract (NTS). Oxycodone treatment significantly increased the number of c-fos-positive neurons in the area postrema and NTS compared with water controls. As expected, cisplatin also increased the number of c-fos-positive cells in these regions. In the area postrema, the oxycodone effect was greater than cisplatin, especially at 2 h. These results indicate that an antinociceptive dose of oxycodone is associated with the expression of pica, a pro-emetic response.

Topics: Analgesics, Opioid; Animals; Antiemetics; Antineoplastic Agents; Brain; Cisplatin; Drug Evaluation, Preclinical; Emetics; Female; Humans; Kaolin; Male; Narcotic Antagonists; Nausea; Oxycodone; Pica; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa; Receptors, Opioid, mu; Sex Characteristics; Time Factors; Vomiting

Topics: Adolescent; Autistic Disorder; Bezoars; Female; Humans; Pica; Stomach; Vomiting

Clinical utility of phosphodiesterase 4 (PDE4) inhibitors as anti-inflammatory agents has, to date, been limited by adverse effects including nausea and emesis, making accurate assessment of emetic versus anti-inflammatory potencies critical to the development of inhibitors with improved therapeutic indices. In the present study we determined the in vitro and in vivo anti-inflammatory potencies of the first-generation PDE4 inhibitor, rolipram, the second-generation inhibitors, roflumilast and cilomilast, and a novel third generation inhibitor, 1-ethyl-5-{5-[(4-methyl-1-piperazinyl)methyl]-1,3,4-oxadiazol-2-yl}-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine (EPPA-1). The rank-order potency against lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha production by human peripheral blood mononuclear cells was roflumilast (IC(50) = 5 nM) > EPPA-1 (38) > rolipram (269) > cilomilast (389), and against LPS-induced pulmonary neutrophilia in the rat was EPPA-1 (D(50) = 0.042 mg/kg) > roflumilast (0.24) > rolipram (3.34) > cilomilast (4.54). Pica, the consumption of non-nutritive substances in response to gastrointestinal stress, was used as a surrogate measure for emesis, giving a rank-order potency of rolipram (D(50) = 0.495 mg/kg) > roflumilast (1.6) > cilomilast (6.4) > EPPA-1 (24.3). The low and high emetogenic activities of EPPA-1 and rolipram, respectively, detected in the pica model were confirmed in a second surrogate model of emesis, reversal of alpha(2)-adrenoceptor-mediated anesthesia in the mouse. The rank order of therapeutic indices derived in the rat [(pica D(50))/(neutrophilia D(50))] was EPPA-1 (578) > roflumilast (6.4) > cilomilast (1.4) > rolipram (0.15), consistent with the rank order derived in the ferret [(emesis D(50))/(neutrophilia D(50))]. These data validate rat pica feeding as a surrogate for PDE4 inhibitor-induced emesis in higher species, and identify EPPA-1 as a novel PDE4 inhibitor with an improved therapeutic index.

Topics: Aminopyridines; Animals; Benzamides; Carboxylic Acids; Cyclohexanecarboxylic Acids; Cyclopropanes; Ferrets; Humans; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Neutrophils; Nitriles; Phosphodiesterase 4 Inhibitors; Phosphodiesterase Inhibitors; Pica; Piperazines; Pyridines; Rats; Rats, Inbred Lew; Receptors, Adrenergic, alpha-2; Rolipram; Tumor Necrosis Factor-alpha; Vomiting

Topics: Animals; Antineoplastic Agents; Carmine; Disease Models, Animal; Kaolin; Mice; Pica; Radiotherapy; Rats; Rats, Wistar; Vomiting

Anticancer agents, such as cisplatin, induce vomiting, nausea, and anorexia. Cisplatin primarily acts on vagal afferents to produce emesis, but little is known about how this drug generates nausea and anorexia. Electrophysiology indicates that cisplatin activates vagal afferents of the common hepatic branch (CHB). Rats lack an emetic response but do ingest kaolin clay (a pica response) when made sick by toxins, and this behavior can be inhibited by antiemetic drugs. It has been postulated that pica may serve as a proxy for emesis in the rat. The goal of this study was to assess the effect of CHB or ventral gastric (Gas) or celiac (Cel) branch vagotomies on pica and anorexia produced by cisplatin in the rat. The effects of apomorphine, a dopamine receptor agonist, which induces emesis via a central mechanism, were also assessed. Cisplatin-induced pica was suppressed by CHB vagotomy (a 61% reduction) but not by Gas and Cel vagotomy. Suppression of daily food intake and body weight following cisplatin treatment was also blunted by CHB ablation but not by Gas or Cel vagotomy. No vagotomy condition exhibited altered apomorphine-induced pica. The results indicate that the CHB, which innervates primarily the duodenum, plays an important role in cisplatin-induced malaise. These data suggest that pica has sensory pathways similar to emetic systems, since a vagotomy condition inhibited cisplatin-induced pica but had no effect on apomorphine-induced pica. This investigation contributes to the delineation of the physiology of pica and neural systems involved in malaise in the nonvomiting rat.

Topics: Animals; Anorexia; Antineoplastic Agents; Apomorphine; Body Weight; Celiac Plexus; Cisplatin; Dopamine Agonists; Drinking; Eating; Kaolin; Liver; Male; Pica; Rats; Rats, Sprague-Dawley; Stomach; Vagotomy; Vomiting

Cancer chemotherapy drugs, such as cisplatin, are extremely potent for producing nausea and vomiting. The acute effects of these treatments are partly controlled using anti-emetic drugs, but the delayed effects (>24 h), especially nausea, are much more difficult to treat. Furthermore, cisplatin induces a long-term (up to 48 h) increase in pica in rats. Pica is manifested as an increase in consumption of kaolin (clay) and is used as a measure of visceral sickness. It is unknown what brain pathways might be responsible for this sickness associated behavior. As a first attempt to define this neural system, rats were injected (i.p.) with 3, 6, or 10 mg/kg cisplatin (doses reported to produce pica) and sacrificed at 6, 24, or 48 h to determine brain Fos expression. The primary results indicate: 1) increasing the dose of cisplatin increased the magnitude and duration of brain Fos expression, 2) most excitatory effects on hindbrain nucleus of the solitary tract (NTS) and area postrema (AP) Fos expression occurred within 24 h after cisplatin injection, 3) 6 and 10 mg/kg cisplatin treatment produced large increases in Fos expression in the central amygdala (CeA) and bed nucleus of the stria terminalis (BNST), including 48 h after injection, and 4) cisplatin treatment produced little effect on Fos expression in the paraventricular and supraoptic nuclei of the hypothalamus. These results indicate that cisplatin activates a neural system that includes the dorsal vagal complex (NTS and AP), CeA, and BNST.

Topics: Animals; Antineoplastic Agents; Brain; Cisplatin; Dose-Response Relationship, Drug; Immunohistochemistry; Male; Nausea; Neural Pathways; Pica; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Vomiting

Cancer chemotherapy is frequently accompanied by severe emesis. The anti-cancer drugs are classified according to their clinical emetogenic potential. We have already found that kaolin ingestion behavior "pica" is analogous to emesis in rats. The aim of this study was to examine the effects of the clinical emetogenic potential of anti-cancer drugs on the induction of the pica in rats. Rats were housed in individual cages with free access to food and kaolin pellets and the daily food and kaolin intakes were measured for 3 days after the intraperitoneal administration of anti-cancer drugs (cisplatin, cyclophosphamide, actinomycin D, 5-fluorouracil and vincristine). The drugs with high potential for inducing emesis, such as cisplatin and cyclophosphamide, induced pica in all animals on the day of administration and the behavior lasted during the observation period. The drugs with moderate emetogenic potential, i.e. actinomycin D and 5-fluorouracil, also induced pica on the first and second day after the drug administration but the kaolin intake was less than that of the drugs with high potential. Vincristine, a drug with low emetogenic potential, slightly increased the kaolin intake in rats on the only first day of the administration. Cyclophosphamide, actinomycin D and vincristine induced anorexia and decreased their body weight during the observation period. These results suggested that the both amounts of kaolin intake and duration of behavior in the anti-cancer drug-induced pica are related to the clinical emetogenic potential of the drugs and the incidence of the anorexia is not related to their emetogenic potential.

Topics: Animals; Anorexia; Antineoplastic Agents; Cisplatin; Dactinomycin; Fluorouracil; Kaolin; Male; Pica; Rats; Rats, Wistar; Vincristine; Vomiting

Ritonavir, a protease inhibitor drug, is commonly used in AIDS therapy. As with other chemotherapeutic drugs that cause gastrointestinal adverse effects, ritonavir treatment is associated with significant nausea and vomiting. This study investigated whether Scutellaria baicalensis, and its active flavonoid constituent, baicalein, attenuate the gastrointestinal effects of ritonavir. The effects of herb administration were evaluated in ritonavir-treated rats using a rat pica model, which simulates nausea and vomiting in humans. The effects of herb administration on gastric emptying in rats were also measured. Ritonavir treatment resulted in increased kaolin intake or severe pica, the intensity of which was reduced significantly with S. baicalensis administration (1 mg kg(-1); P<0.05). High-performance liquid chromatography analysis of S. baicalensis showed the presence of an extremely potent flavonoid constituent, baicalein. The study aimed to determine if baicalein contributed to the anti-pica effect of the extract. It was observed that baicalein dose-dependently decreased pica in ritonavir-treated rats (P<0.001). In addition to inducing pica, ritonavir also significantly delayed gastric emptying, which could contribute to ritonavir-induced gastrointestinal dysfunction. When S. baicalensis extract was administered to ritonavir-treated rats the delayed gastric emptying was significantly attenuated (P<0.05). The results suggest that S. baicalensis and the constituent baicalein reduce the gastrointestinal dysfunction caused by ritonavir. It is concluded that S. baicalensis may potentially have a role to play in reducing drug-induced adverse effects.

Topics: Animals; Antiemetics; Antioxidants; Disease Models, Animal; Dose-Response Relationship, Drug; Flavanones; Flavonoids; Gastric Emptying; HIV Protease Inhibitors; Kaolin; Male; Nausea; Pica; Plant Extracts; Plant Roots; Rats; Rats, Wistar; Ritonavir; Scutellaria baicalensis; Vomiting

Topics: Animals; Cisplatin; Injections, Intraperitoneal; Kaolin; Neurokinin-1 Receptor Antagonists; Pharmacology; Pica; Piperidines; Rats; Vomiting

Cisplatin, a chemotherapeutic agent, causes significant nausea and vomiting. It is postulated that cisplatin-induced oxidant stress may be responsible for these symptoms. We tested whether pretreatment with American ginseng berry extract (AGBE), an herb with potent antioxidant capacity, and one of its active antioxidant constituents, ginsenoside Re, could counter cisplatin-induced emesis using a rat pica model.. In rats, exposure to emetic stimuli such as cisplatin causes significant kaolin intake, a phenomenon called pica. We therefore measured cisplatin-induced kaolin intake as an indicator of the emetic response. Rats were pretreated with vehicle, AGBE (dose range 50-150 mg/kg, IP) or ginsenoside Re (2 and 5 mg/kg, IP). Rats were treated with cisplatin (3 mg/kg, IP) 30 min later. Kaolin intake, food intake, and body weight were measured every 24 h for 120 h. Additionally, the free radical scavenging activity of AGBE was measured in vitro using ESR spectroscopy.. A significant dose-response relationship was observed between increasing doses of pretreatment with AGBE and reduction in cisplatin-induced pica. Kaolin intake was maximally attenuated by AGBE at a dose of 100 mg/kg. Food intake also improved significantly at this dose (P<0.05). Pretreatment with ginsenoside Re (5 mg/kg) also decreased kaolin intake (P<0.05). In vitro studies demonstrated a concentration-response relationship between AGBE and its ability to scavenge superoxide and hydroxyl radicals.. Pretreatment with AGBE and its major constituent, Re, attenuated cisplatin-induced pica, and demonstrated potential for the treatment of chemotherapy-induced nausea and vomiting. Significant recovery of food intake further strengthens the conclusion that AGBE may exert an antinausea/antiemetic effect.

Topics: Animals; Antidiarrheals; Antineoplastic Agents; Antioxidants; Cisplatin; Disease Models, Animal; Ginsenosides; Kaolin; Male; Oxidative Stress; Panax; Pica; Plant Extracts; Rats; Rats, Wistar; Vomiting

During the course of studies investigating novel anti-emetic therapies we serendipitously observed a previously unreported behaviour related to emesis in the house musk shrew. This behaviour consisted of spontaneous ingestion of vomit in about half of the animals (males and females) in which emesis was induced by either nicotine (4 mg kg-1 sc.) or horizontal motion (1 Hz, 4 cm, 10 min). Analysis of vomit samples and gastric contents revealed that in a "typical" individual the gastric contents would be voided by as few as 3 vomits. Energetic calculations of the metabolisable energy of food, gastric contents, vomit and field metabolic rate (FMR) predict that a male weighing 60 g would lose 17.3% of its hourly energy requirement for FMR if it vomited once. A 40 g female, however, would experience an hourly energy loss of approximately 22.8%. The possible energetic consequences and resulting ecological implications of this unusual behaviour are discussed.

Topics: Animals; Disease Models, Animal; Energy Intake; Energy Metabolism; Feeding Behavior; Female; Male; Motion Sickness; Nicotine; Pica; Shrews; Vomiting

Grape-seed (Vitis spp.) extract (GSE) is a widely used antioxidant dietary supplement. Chemotherapeutic agents such as cisplatin induce oxidative damage in the gastrointestinal tract and cause nausea and vomiting.. A rat model of simulated emesis was used to observe that cisplatin significantly increased kaolin consumption (or pica). Three GSEs from different sources were used in this study.. High-performance liquid chromatographic analysis of five major constituents (gallic acid, catechin, epicatechi, procyanidin B2, and epicatechin gallate) revealed that each constituent had different levels in the three GSEs. Extract #1, prepared in the laboratory of the investigators, had the lowest total polyphenol content (27.27 mg/g); Extract #2, obtained from a dietary supplement company in the United States, had a somewhat higher level (35.84 mg/g); and Extract #3, obtained from China, had the highest level (194.21 mg/g). Subsequently these GSEs were intraperitoneally administered in rats to evaluate their ability to decreasing cisplatin induced pica. At 10 mg/kg all three GSEs, with varying degrees of effect, decreased cisplatin-induced pica. The areas under the curves of kaolin intake from time 0 to 72 hours, compared to those in the cisplantin-only group, were reduced 45% for Extract #1 (p < 0.01), 54% for Extract #2 (p < 0.01), and 66% Extract #3 (p < 0.001).. The study data showed variable polyphenol contents and proportions in the three GSEs correlated to variable pharmacologic effects, indicating the importance of standardization of herbal product preparations. However further increasing of the GSE doses reversed the antipica effects of GSEs, probably because of their pro-oxidant effects. Results from this study suggest that an appropriate dose of GSE has therapeutic value in treating cisplatin-induced emesis.

Topics: Animals; Antiemetics; Antioxidants; Area Under Curve; Cisplatin; Disease Models, Animal; Dose-Response Relationship, Drug; Flavonoids; Male; Nausea; Phenols; Phytotherapy; Pica; Plant Extracts; Polyphenols; Rats; Rats, Wistar; Seeds; Vitis; Vomiting

Nausea and vomiting are significant adverse effects of chemotherapeutic agents like cisplatin, and cause significant patient morbidity. Cisplatin treatment results in oxidant gut injury, which is postulated to be the primary cause of nausea and vomiting. We evaluated the effects of two antioxidant herbs, Scutellaria baicalensis and American ginseng berry, on cisplatin-induced nausea and vomiting using a rat model. Rats react to emetic or nausea-producing stimuli, such as cisplatin, with altered feeding habits, manifested by increased kaolin consumption (pica). We measured pica in rats to quantify cisplatin-induced nausea. We observed that pretreatment of rats with S. baicalensis or ginseng berry extracts resulted in a significant reduction in cisplatin-induced pica. The in vitro free radical scavenging ability of the herbal extract observed in the study, further confirmed the antioxidant action of the herb. We conclude that herbal antioxidants may have a role in attenuating cisplatin-induced nausea and vomiting.

Topics: Animals; Antineoplastic Agents; Antioxidants; Cisplatin; Disease Models, Animal; Free Radical Scavengers; Male; Nausea; Panax; Phytotherapy; Pica; Plant Extracts; Rats; Rats, Wistar; Scutellaria; Vomiting

Topics: Abdomen, Acute; Adult; Diarrhea; Digestive System Surgical Procedures; Female; Foreign Bodies; Humans; Intestine, Small; Ischemia; Pica; Treatment Outcome; Vomiting

We previously reported that the concentration of 5-hydroxytryptamine (5-HT) in the brainstem of cisplatin-administered ferrets is significantly increased as compared with that of control animals. In an attempt to clarify the mechanisms of emesis induced by cytotoxic drugs, we measured kaolin ingestion (pica) and the tissue concentrations of 5-HT, norepinephrine (NE) and dopamine in various brain regions of rats after cisplatin administration. 5-HT concentrations in the hippocampus, the medulla oblongata and the hypothalamus significantly increased 72 hours after a single dose administration of cisplatin (5 mg/kg, i.p.) compared with those of control rats. NE concentration in the hippocampus significantly increased simultaneously with kaolin ingestion in cisplatin-treated rats. These results suggest that higher brain regions such as the hippocampus and the hypothalamus are involved in cisplatin-induced emesis.

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Antineoplastic Agents; Brain; Cisplatin; Dopamine; Hydroxyindoleacetic Acid; Kaolin; Male; Norepinephrine; Pica; Rats; Rats, Wistar; Serotonin; Sympathomimetics; Vomiting

We investigated whether radiation-induced pica, a behavior characterized by the eating of a non-food substance, such as kaolin, can be used as an index of radiation-induced vomiting in rats. Since there was an individual difference in the susceptibility to pica, we selected rats that actually ate kaolin following X-ray irradiation, and used them for the experiment. The total-body irradiation (TBI) increased kaolin consumption in a dose-dependent manner (sham, 0.05 +/- 0.03 (SEM) g; 2 Gy, 0.38 +/- 0.11 g; 4 Gy, 1.54 +/- 0.28 g; 8 Gy, 3.55 +/- 0.67 g), and the increased kaolin consumption after 4 Gy of TBI was inhibited by a pretreatment with the serotonin 5-HT3 receptor antagonist ondansetron (2 mg/kg, i.p.) (saline, 1.49 +/- 0.33 g; ondansetron, 0.75 +/- 0.11 g). Furthermore, 4 Gy of abdominal irradiation was more effective to induce pica than that of head irradiation (abdomen: 0.37 +/- 0.05 g, head: 0.06 +/- 0.01 g). These findings suggested that peripheral serotonergic pathway is predominantly involved in the development of radiation-induced pica in rats and that the radiation-induced pica could be useful as a behavioral index for the severity of radiation-induced vomiting in rats.

Topics: Animals; Disease Models, Animal; Male; Pica; Radiation Injuries; Rats; Rats, Wistar; Vomiting; Whole-Body Irradiation

In general, rats and mice have not been used in research on emesis because they do not vomit. However, emetogenic stimuli such as anticancer drugs, apomorphine, copper sulfate and rotation induced pica, a behavior characterized by eating nonfood substances such as kaolin, in rats. We also found that cisplatin induced pica in mice, but it was rather difficult to determine the exact kaolin consumption in this species. In this study, we prepared kaolin pellets mixed with carmine, a dye not absorbed in the gastrointestinal tract, and estimated kaolin consumption by determination of carmine excreted in feces. Cisplatin (5 mg/kg) caused a significant increase in kaolin consumption (saline: 0.15 +/- 0.08 g vs. cisplatin: 0.45 +/- 0.16 g) and pretreatment with the 5-HT3 receptor antagonist, ondansetron (2 mg/kg), suppressed the increased consumption (vehicle: 0.33 +/- 0.05 g vs. ondansetron: 0.13 +/- 0.04 g). These findings suggested that the exact kaolin consumption could be quantified by the determination of carmine in feces and that mice could be useful for studying emesis.

Topics: Animals; Antiemetics; Antineoplastic Agents; Carmine; Cisplatin; Disease Models, Animal; Eating; Feces; Kaolin; Male; Mice; Mice, Inbred ICR; Ondansetron; Pica; Vomiting

The effects of a novel tachykinin NK1-receptor antagonist HSP-117 [(2S,3S)-3-[(5-isopropyl-2,3-dihydrobenzofuran-7-yl)methyl]amino-2-phenylpiperidine dihydrochloride] on cisplatin-induced pica, i.e., the eating of nonnutritive substances such as kaolin were examined in rats. HSP-117 inhibited kaolin intake in a dose-dependent manner for 2 days. The 5-HT3-receptor antagonist ondansetron inhibited only on the first day, but not on the second day. These results indicate that the cisplatin-induced kaolin intake on the first day is related to both 5-HT3- and NK1 receptors, while only the NK1 receptor is involved on the second day. Thus, cisplatin-induced continuous pica in rats represents a useful model of not only acute but also delayed emesis.

Topics: Animals; Antineoplastic Agents; Benzofurans; Cisplatin; Humans; Neurokinin-1 Receptor Antagonists; Pica; Piperidines; Rats; Rats, Wistar; Vomiting

In a direct test of conditioned antisickness (CAS; B. T. Lett, 1983) theory, the authors measured emesis in ferrets and found those with a history of forward pairings of pentobarbital and lithium to have fewer and shorter bouts of emesis on test, whether induced by lithium or, in a subsequent test, by the highly emetogenic anticancer drug cisplatin. In an indirect test of her CAS theory, B. T. Lett (1992) paired interoceptive (drug) or place cues with lithium chloride toxicosis and found that rats with a forward-pairings history ate less food than controls on a forward-pairing test, consistent with conditioned sickness rather than CAS. But rats eat dirt or clay in response to sickness and adaptively eat small amounts of food when clay is not available. We substituted clay (kaolin) for food in a partial procedural replication of B. T. Lett's (1992, Experiment 1) experiment and found that rats with a history of forward pairings of pentobarbital and lithium ate less kaolin, which is consistent with CAS.

Topics: Animals; Association Learning; Avoidance Learning; Conditioning, Classical; Emetics; Ferrets; Kaolin; Male; Nausea; Pica; Rats; Rats, Sprague-Dawley; Species Specificity; Taste; Vomiting

The objective of our study was to assess the demographics, incidence, types of symptoms, and outcomes of cigarette product ingestions in children. The study was a retrospective database review. Seven hundred children under six years of age ingesting cigarettes or cigarette butts reported to a Poison Control Center between 1988 and 1991. Among 143 patients (20.4%) with symptoms, vomiting was the only symptom in 138 (98.6%) and occurred in less than 20 minutes in 104 (74.3%). The five remaining patients (two with vomiting, three without) developed transient lethargy or irritability that completely resolved. Forty-four of 700 patients ingested potentially toxic amounts and were referred to the emergency department; three were lost to follow-up. Initially asymptomatic patients never developed symptoms. Symptomatic patients improved without sequelae. No patient developed seizures. We concluded that significant toxicity from the ingestion of cigarette products in children is rare. Vomiting within 20 minutes is the most common symptom. Its absence predicts a favorable outcome, even when large amounts are suspected to have been ingested.

Topics: Decision Trees; Female; Follow-Up Studies; Humans; Incidence; Infant; Male; Nicotiana; Pica; Plants, Toxic; Retrospective Studies; Severity of Illness Index; Sleep Stages; Treatment Outcome; Vomiting

The effects of diphenhydramine, domperidone, ondansetron, and diphenidol on cisplatin-induced pica (i.e., kaolin ingestion) in rats as the measure analogous to emesis in other species were examined. Ondansetron (2 mg/kg) and diphenidol (30 mg/kg) inhibited kaolin intake induced by cisplatin (10 mg/kg), but diphenhydramine and domperidone did not. Diphenhydramine and diphenidol have been shown to inhibit kaolin intake induced by double rotation, while domperidone and ondansetron did not, and kaolin intake induced by apomorphine was inhibited by domperidone and diphenidol, but not by diphenhydramine or ondansetron. These observations, together with the present findings, suggest that the emetic pathways through the inner ear (double rotation), chemoreceptor trigger zone (apomorphine) and visceral afferent (cisplatin), are pharmacologically independent and are mediated by histamine H1 receptors, dopamine D2 receptors and serotonin 5-HT3 receptors, respectively. It is conceivable that diphenidol may inhibit the emetic center itself, although the receptor on which it acts is not known.

Topics: Animal Feed; Animals; Antiemetics; Antineoplastic Agents; Cisplatin; Eating; Kaolin; Male; Pica; Rats; Rats, Wistar; Vomiting

Mitchell et al. (1976, 1977) suggested that pica, eating of nonnutritive substances such as kaolin, is an illness-response behavior in rats. In the present study, we first confirmed their suggestion and then examined the effects of antiemetics on emetic-induced pica in rats. Intraperitoneal injection of apomorphine induced dose-dependent kaolin consumption. Pretreatment with domperidone inhibited apomorphine-induced kaolin intake. Oral administration of copper sulfate and intraperitoneal injection of cisplatin also induced dose-dependent kaolin consumption. Pretreatment with ondansetron inhibited cisplatin-induced kaolin intake. These findings suggest that pica in rats was induced through 1) dopamine D2 receptors in the chemoreceptor trigger zone, and 2) the stomach, partly via 5-HT3 receptors in the visceral afferents in the stomach wall. The present findings support the conclusion that pica in rats is analogous to vomiting in other species and suggest that pica in rats is mediated by the same mechanisms as vomiting in humans. Accordingly, we extended the utility of the animal model to pharmacological research of emesis with pica as an analogue to emesis.

Topics: Animals; Antiemetics; Apomorphine; Cisplatin; Copper; Copper Sulfate; Disease Models, Animal; Domperidone; Dose-Response Relationship, Drug; Food; Kaolin; Male; Ondansetron; Pica; Rats; Rats, Wistar; Vomiting

Using kaolin intake as a behavioral index of emesis in rats, we examined the relationship between susceptibility to motion sickness and to emesis induced by apomorphine or copper sulfate. Rats showed a wide variation in susceptibility to motion sickness. Significant positive correlations were found between susceptibility to motion sickness and to emesis induced by intraperitoneal administration of apomorphine and by oral administration of copper sulfate. Motion, apomorphine and copper sulfate induce emesis through different receptors, so these findings suggest that the sensitivity of a common locus of emesis, presumably the emetic center in the brain stem, is one determinant of individual differences in susceptibility to motion sickness.

Topics: Animals; Apomorphine; Brain; Copper; Copper Sulfate; Disease Susceptibility; Kaolin; Male; Motion; Motion Sickness; Pica; Rats; Rats, Wistar; Sensory Thresholds; Stomach; Vestibule, Labyrinth; Vomiting

Frequency and severity of nausea and of vomiting during pregnancy, and of pronounced dietary cravings and aversions, were determined in a series of South African rural and urban black, Indian, coloured (European-African-Malay) and white women. Frequency of severe nausea ranged from 3.8% in rural blacks to 19.8% in white women, and of severe vomiting from 3.1% in rural blacks to 17.8% in white and Indian women. Proportions in the other groups were intermediate. Pronounced cravings, claimed by 67-84% in the various groups, included sour, savoury and sweet foods, also fruit and milk. Aversions were claimed by 45-81% of the women in the different groups with meat, fish, coffee and fatty foods, the foods most often avoided. Pica, the consumption of such substances as earth, clay, varied ethnically and regionally; frequency was high in rural and urban black women (44.0% and 38.3%), but much lower (5%) in Indian, coloured and white women.

Topics: Adult; Asian People; Black People; Female; Food Preferences; Humans; Nausea; Pica; Pregnancy; Pregnancy Complications; Rural Population; South Africa; Twins; Urban Population; Vomiting; White People

Before 1949, the vomiting center was said to be located in the dorsal vagal nuclei of the medulla, but it was uncertain whether two centers existed separately for the control of direct and reflex actions of emetic agents. Borison and Wang then used a stereotaxic technique with electrical stimulation to localize the vomiting center in the reticular formation at a measurable distance from the dorsal vagal nuclei. They also formulated the concept of a separate emetic chemoreceptor trigger zone (CTZ) so that the vomiting center itself is not sensitive to emetic agents and serves solely to coordinate the reflex process. The CTZ was soon identified with the area postrema (AP), but the question remains unanswered whether the CTZ constitutes part or all of tht circumventricular organ. Furthermore, different chemosensory functions, as for defecation and certain forms of autonomic expression, may be represented regionally within the AP. Species that are unable to vomit, e.g., rodents, show other postrema-mediated effects as radiation-induced gastric stasis and drug-induced conditioned taste aversion. In sheep, digitalis-induced arrest of rumination is prevented by postremectomy. It is suggested that these behavioral end points in nonvomiting species may serve for biological assay of antinauseant drugs. Finally, a tabular summary is given of known causes of vomiting in which the AP has been implicated.

Topics: Animals; Artiodactyla; Cats; Cerebral Ventricles; Chemoreceptor Cells; Defecation; Dogs; Emetics; Gastric Emptying; Humans; Medulla Oblongata; Pica; Taste; Vomiting

Three interrelated symptom ' complexes' are implicated in dietary changes during pregnancy: nausea and vomiting of pregnancy (NVP), dietary aversions, and dietary cravings. These are discussed with particular emphasis on NVP and the fate of the fetus.

Topics: Diet; Female; Fetus; Food; Food Preferences; Humans; Nausea; Nutritional Requirements; Pica; Pregnancy; Pregnancy Complications; Vomiting

Topics: Animals; Behavior, Animal; Disease Models, Animal; Habituation, Psychophysiologic; Humans; Kaolin; Male; Motion Sickness; Pica; Rats; Rotation; Species Specificity; Vomiting

Topics: Ambulatory Care; Angioedema; Blood Chemical Analysis; Child; Child, Preschool; Diarrhea; Dimercaprol; Edetic Acid; Female; Hematocrit; Humans; Infant; Lead Poisoning; Male; Outpatient Clinics, Hospital; Paint; Penicillamine; Pica; Radiography; Urticaria; Vomiting

Topics: Adolescent; Feeding and Eating Disorders; Feeding Behavior; Female; Hair; Humans; Menstruation; Obsessive-Compulsive Disorder; Paraphilic Disorders; Parent-Child Relations; Pica; Psychoanalytic Therapy; Sexual Behavior; Vomiting