pica and Anorexia

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

The cytokine, GDF15, is produced in pathological states which cause cellular stress, including cancer. When over expressed, it causes dramatic weight reduction, suggesting a role in disease-related anorexia. Here, we demonstrate that the GDF15 receptor, GFRAL, is located in a subset of cholecystokinin neurons which span the area postrema and the nucleus of the tractus solitarius of the mouse. GDF15 activates GFRAL

Topics: Animals; Anorexia; Brain Stem; Cholecystokinin; Growth Differentiation Factor 15; Male; Mice; Mice, Inbred C57BL; Neurons; Pica; Random Allocation; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Signal Transduction

The most common side effects of the cancer chemotherapy drug cisplatin are nausea and vomiting. These effects are heavily influenced by orexigenic and anorexigenic peptides. We explored the effects of orexin-A on the cisplatin-treated rats and a possible mechanism for its effects on cisplatin-induced side effects. Quantitative real-time PCR was used to measure the change of prepro-orexin mRNA in the hypothalamus following cisplatin treatment. The effect of orexin-A and cisplatin on the firing rate of arcuate nucleus neurons was recorded. The effect of administration of orexin-A and a neuropeptide Y1 receptor antagonist to the arcuate nucleus on food intake, pica, and gastric motility on cisplatin treated rats were also measured. The relative expression of prepro-orexin mRNA in the hypothalamus was reduced by cisplatin. Exogenous orexin-A altered cisplatin-induced changes to the neuronal firing of gastric distension-responsive neurons, alleviated the cisplatin-induced anorexia, pica and improves the weakened gastric motility in the arcuate nucleus of rats. These effects could be partially blocked by intracerebroventricular injection (i.c.v.) of a neuropeptide Y1 receptor antagonist. These results suggest that orexin-A signaling ameliorates the gastric disorder induced by cisplatin in rats, and may act through neuropeptide Y neurons in the arcuate nucleus.

Topics: Action Potentials; Animals; Anorexia; Arcuate Nucleus of Hypothalamus; Arginine; Cisplatin; Eating; Gastric Emptying; Gastrointestinal Motility; Infusions, Intraventricular; Male; Neurons; Orexins; Pica; Random Allocation; Rats; Rats, Wistar; Receptors, Neuropeptide Y; RNA, Messenger; Stomach

The overlap in neurobiological circuitry mediating the physiological and behavioral response to satiation and noxious/stressful stimuli are not well understood. The interaction between serotonin (5-HT) and glucagon-like peptide-1 (GLP-1) could play a role as upstream effectors involved in mediating associations between anorectic and noxious/stressful stimuli. We hypothesize that 5-HT acts as an endogenous modulator of the central GLP-1 system to mediate satiation and malaise in rats. Here, we investigate whether interactions between central 5-HT and GLP-1 signaling are behaviorally and physiologically relevant for the control of food intake and pica (i.e., behavioral measure of malaise). Results show that the anorexia and body weight changes induced by administration of exogenous hindbrain 5-HT are dependent on central GLP-1 receptor signaling. Furthermore, anatomical evidence shows mRNA expression of 5-HT2C and 5-HT3 receptors on GLP-1-producing preproglucagon (PPG) neurons in the medial nucleus tractus solitarius by fluorescent in situ hybridization, suggesting that PPG neurons are likely to express both of these receptors. Behaviorally, the hypophagia induced by the pharmacological activation of both of these receptors is also dependent on GLP-1 signaling. Finally, 5-HT3, but not 5-HT2C receptors, are required for the anorectic effects of the interoceptive stressor LiCl, suggesting the hypophagia induced by these 5-HT receptors may be driven by different mechanisms. Our findings highlight 5-HT as a novel endogenous modulator of the central GLP-1 system and suggest that the central interaction between 5-HT and GLP-1 is involved in the control of food intake in rats.

Topics: Animals; Anorexia; Feeding Behavior; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Lithium Chloride; Male; Neurons; Ondansetron; Peptide Fragments; Pica; Proglucagon; Rats; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin, 5-HT3; Rhombencephalon; Serotonin; Serotonin 5-HT2 Receptor Agonists; Serotonin 5-HT3 Receptor Agonists; Serotonin 5-HT3 Receptor Antagonists; Signal Transduction; Solitary Nucleus; Stress, Psychological; Weight Loss

While chemotherapy-induced nausea and vomiting are clinically controlled in the acute (<24 h) phase following treatment, the anorexia, nausea, fatigue, and other illness-type behaviors during the delayed phase (>24 h) of chemotherapy are largely uncontrolled. As the hindbrain glucagon-like peptide-1 (GLP-1) system contributes to energy balance and mediates aversive and stressful stimuli, here we examine the hypothesis that hindbrain GLP-1 signaling mediates aspects of chemotherapy-induced nausea and reductions in feeding behavior in rats. Specifically, hindbrain GLP-1 receptor (GLP-1R) blockade, via 4th intracerebroventricular (ICV) exendin-(9-39) injections, attenuates the anorexia, body weight reduction, and pica (nausea-induced ingestion of kaolin clay) elicited by cisplatin chemotherapy during the delayed phase (48 h) of chemotherapy-induced nausea. Additionally, the present data provide evidence that the central GLP-1-producing preproglucagon neurons in the nucleus tractus solitarius (NTS) of the caudal brainstem are activated by cisplatin during the delayed phase of chemotherapy-induced nausea, as cisplatin led to a significant increase in c-Fos immunoreactivity in NTS GLP-1-immunoreactive neurons. These data support a growing body of literature suggesting that the central GLP-1 system may be a potential pharmaceutical target for adjunct anti-emetics used to treat the delayed-phase of nausea and emesis, anorexia, and body weight loss that accompany chemotherapy treatments.

Topics: Animals; Anorexia; Body Weight; Cisplatin; Glucagon-Like Peptide-1 Receptor; Infusions, Intraventricular; Male; Nausea; Neurons; Peptide Fragments; Pica; Proglucagon; Rats; Rhombencephalon; Solitary Nucleus

Intermittent subcutaneous injection of teriparatide, an active fragment of human parathyroid hormone, is clinically used for the treatment of osteoporosis. Patients suffer from nausea, which is one of the side effects teriparatide induces; however, the etiology of teriparatide-induced nausea remains unknown. We have reported pica, kaolin ingestion behavior, can be used as an assessment of nausea-related response in rats. In this study, we investigated the characteristics of teriparatide-induced pica and the abilities of anti-emetic drugs to inhibit teriparatide-induced pica. Male and female adolescent (4-week-old), young (8-week-old), and adult (30-week-old) naive rats, and ovariectomized (OVX: 17-week-old) and sham-operated (17-week-old) rats subcutaneously received teriparatide (0.4 mg/kg, n=4), and their kaolin and food intakes were monitored for 24 h after the injection. Among the tested rats, we found that OVX rats, rather than male, female, and sham-operated rats, showed marked teriparatide-induced pica (0 mg/kg: 0.17±0.07 g, 0.4 mg/kg: 6.18±0.91 g). Teriparatide-induced pica in OVX rats was inhibited by intraperitoneal pretreatment with serotonin 5-HT3 (granisetron 0.5 mg/kg), dopamine D2 (prochlorperazine 0.5 mg/kg), neurokinin NK1 (fosaprepitant 1 mg/kg), and histamine H1 (diphenhydramine 10 mg/kg) receptor antagonists to 70%, 11%, 19%, and 59% of that in vehicle-treated control, respectively. These results suggest that teriparatide-induced pica in OVX rats has the potential to reflect teriparatide-induced nausea; 5-HT3, D2, NK1, and H1 receptor activation is involved in the development of this behavior; antagonists of these receptors have the potential to be medical candidates used as treatments for teriparatide-induced nausea in human patients.

Topics: Age Factors; Animals; Anorexia; Antiemetics; Diphenhydramine; Disease Models, Animal; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Eating; Feeding Behavior; Female; Granisetron; Histamine H1 Antagonists; Kaolin; Male; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Neurotransmitter Agents; Ovariectomy; Pica; Prochlorperazine; Rats, Wistar; Serotonin 5-HT3 Receptor Antagonists; Teriparatide

This study investigated the prevalence of iron-deficiency anaemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency and β-thalassaemia trait among Arab migrating nomad children in southern Islamic Republic of Iran. Blood samples were analysed from 134 schoolchildren aged < 18 years (51 males, 83 females). Low serum ferritin (< 12 ng/dL) was present in 17.9% of children (21.7% in females and 11.8% in males). Low haemoglobin (Hb) correlated significantly with a low serum ferritin. Only 1 child had G6PD deficiency. A total of 9.7% of children had HbA2 ≥ 3.5 g/dL, indicating β-thalassaemia trait (10.8% in females and 7.8% in males). Mean serum iron, serum ferritin and total iron binding capacity were similar in males and females. Serum ferritin index was as accurate as Hb index in the diagnosis of iron-deficiency anaemia. A high prevalence of β-thalassaemia trait was the major potential risk factor in this population.. انتشار الثلاسيميَّة، وفقر الدم بعوز الحديد، وعوز نازعة هيدْرُجين الغلوكوز -6- فُسْفات بين أطفال البدو المهاجرين العرب، جنوب جمهورية إيران الإسلامية. مهدي باسالار، داوود مهرباني، عبد الرضا أفراسيابي، زهرة مهرآور، إيرما ريحاني، رقية حميدي، مهران كريمي. لقد تم في هذه الدراسة الاستقصاءُ عن انتشار فقر الدم بعوز الحديد، وعوز نازعة هيدْرُجين الغلوكوز –6– فُسْفات (G6PD)، وخَلَّة الثلاسيمية بيتا بين أطفال البدو المهاجرين العرب في جنوب جمهورية إيران الإسامية. حيث تم تحليل عينات دم من 134 طفاً من أطفال المدارس الذين تقل أعمارهم عن 18 عاماً (51 ذكور، 83 إناث). فوُجد انخفاض في فيرِّيتين المصل (<12 نانوغرام/دل) لدى 17.9% من الأطفال (21.7% لدى الإناث و 11.8% لدى الذكور). وكان انخفاض خضاب الدم (الهيموغلوبين) مرتبطاً – بشكل كبير – مع انخفاض فيرِّيتين المصل. وكان لدى طفل واحد فقط عوز في عوز نازعة هيدروجين الغلوكوز –6– فوسفات. وكان الخضاب 3.5 ≥ HbA2 غ/دل لدى 9.7% من مجموع الأطفال، مما يدل على وجود خلة الثلاسيمية بيتا (10.8% لدى الإناث و 7.8% لدى الذكور). وكان هناك تشابه بين الخضاب في متوسط حديد المصل وفيرِّيتن المصل والسعة الإجمالية الرابطة للحديد لدى الذكور والإناث. وكان لمؤشر فيرِّيتن المصل نفس دقة مؤشر الهيموغلوبين في تشخيص فقر الدم بعوز الحديد. وكان ارتفاع معدل انتشار خلة الثلاسيمية بيتا يمثّل عاملَ الخطر المحتمل الرئيي لدى هذه الفئة من السكان.. Prévalence de la thalassémie, de l'anémie ferriprive et du déficit en glucose-6-phosphate déshydrogénase chez des enfants nomades et migrants arabes (sud de la République islamique d'Iran).. La présente étude a évalué la prévalence de l'anémie ferriprive, du déficit en glucose-6-phosphate déshydrogénase et de la bêta-thalassémie mineure chez des enfants nomades et migrants arabes dans le sud de la République islamique d'Iran. Des échantillons de sang de 134 écoliers de moins de 18 ans ont été analysés (51 garçons, 83 filles). Des taux de ferritine sérique faibles (< 12 ng/dL) ont été observés chez 17,9 % des enfants (21,7 % chez les filles et 11,8 % chez les garçons). Un faible taux d'hémoglobine (Hb) était significativement corrélé à un faible taux de ferritine sérique. Seul un enfant était atteint de déficit en glucose-6-phosphate déshydrogénase. Au total, 9,7 % des enfants présentaient un taux d’HbA2 supérieur ou égal à 3,5 g/dL, signe d'une bêta-thalassémie mineure (10,8 % des filles et 7,8 % des garçons). Le taux moyen de fer sérique, de la ferritine sérique et la capacité de liaison du fer total étaient similaires chez les deux sexes. Le taux de ferritine sérique était aussi précis que le taux d’Hb pour le diagnostic de l'anémie ferriprive. La forte prévalence de la bêta-thalassémie mineure représentait le principal facteur de risque dans cette population.

Topics: Adolescent; Anemia, Iron-Deficiency; Anorexia; Arabs; beta-Thalassemia; Child; Cross-Sectional Studies; Female; Ferritins; Genetic Predisposition to Disease; Glucosephosphate Dehydrogenase Deficiency; Hemoglobin A2; Humans; Iran; Iron; Male; Pica; Prevalence; Risk Factors; Transients and Migrants; Water Supply

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

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 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

Zinc concentrations in plasma and hair were measured in 703 children, aged between 1 and 6 yr, and correlated with parameters of physical development. In the first group of 187 children brought to the Child Health Clinic for routine observation there was a positive correlation of hair zinc content and height for age, with an increased prevalence of low hair zinc content in children of shorter stature. A second group of 303 children in nurseries and kindergartens in Beijing exhibited a hair zinc content of 92 micrograms/g, and 34% of these had very low zinc values below 70 micrograms/g. The third group consisted of 213 children who were brought into the outpatient clinic for a variety of complaints, including pica, anorexia, and poor growth; these had significantly lower values of zinc in hair and plasma than well-nourished children and responded to zinc supplementation with improvement of growth and the disappearance of pica and anorexia. These results suggest that the diet consumed by the population studied may be marginal or inadequate in its content of available zinc.

Topics: Anorexia; Child, Preschool; China; Feeding and Eating Disorders; Female; Growth; Growth Disorders; Hair; Humans; Infant; Male; Pica; Sulfates; Zinc; Zinc Sulfate

Topics: Animals; Animals, Domestic; Anorexia; Cat Diseases; Cats; Coprophagia; Dog Diseases; Dogs; Drinking; Feeding and Eating Disorders; Feeding Behavior; Garbage; Humans; Obesity; Pica; Plants; Predatory Behavior; Sucking Behavior; Wool