Involvement of leukotriene pathway in the development of sevoflurane-induced pica in rats.

We previously reported that sevoflurane-induced pica, kaolin ingestion behavior, in rats has the potential to reflect postoperative nausea and vomiting (PONV) in humans. It is well-known that corticosteroids, which inhibit both prostaglandin and leukotriene syntheses due to phospholipase A2 inhibition, are effective for reducing PONV; however, the precise mechanisms remain unclear. We investigated the involvement of the prostaglandin or leukotriene pathway in the development of sevoflurane-induced pica. We found that sevoflurane-induced pica was effectively inhibited by pretreatment with a leukotriene receptor antagonist (montelukast) or an inhibitor of 5-lipoxygenase (zileuton), rather than an inhibitor of cyclooxygenase (flurbiprofen). Furthermore, we observed that sevoflurane significantly increased urinary leukotriene excretion and 5-lipoxygenase mRNA expression in the spleen, but not hypothalamus. These results suggest that the production of leukotriene may lead to the development of sevoflurane-induced pica in rats, and that inhibition of the leukotriene pathway could be potentially useful for the treatment of PONV.

Glutamate Receptors in the Central Nucleus of the Amygdala Mediate Cisplatin-Induced Malaise and Energy Balance Dysregulation through Direct Hindbrain Projections.

Cisplatin chemotherapy is used commonly to treat a variety of cancers despite severe side effects such as nausea, vomiting, and anorexia that compromise quality of life and limit treatment adherence. The neural mechanisms mediating these side effects remain elusive despite decades of clinical use. Recent data highlight the dorsal vagal complex (DVC), lateral parabrachial nucleus (lPBN), and central nucleus of the amygdala (CeA) as potential sites of action in mediating the side effects of cisplatin. Here, results from immunohistochemical studies in rats identified a population of cisplatin-activated DVC neurons that project to the lPBN and a population of cisplatin-activated lPBN calcitonin gene-related peptide (CGRP, a marker for glutamatergic neurons in the lPBN) neurons that project to the CeA, outlining a neuroanatomical circuit that is activated by cisplatin. CeA gene expressions of AMPA and NMDA glutamate receptor subunits were markedly increased after cisplatin treatment, suggesting that CeA glutamate receptor signaling plays a role in mediating cisplatin side effects. Consistent with gene expression results, behavioral/pharmacological data showed that CeA AMPA/kainate receptor blockade attenuates cisplatin-induced pica (a proxy for nausea/behavioral malaise in nonvomiting laboratory rodents) and that CeA NMDA receptor blockade attenuates cisplatin-induced anorexia and body weight loss in addition to pica, demonstrating that glutamate receptor signaling in the CeA is critical for the energy balance dysregulation caused by cisplatin treatment. Together, these data highlight a novel circuit and CGRP/glutamatergic mechanism through which cisplatin-induced malaise and energy balance dysregulation are mediated. SIGNIFICANCE STATEMENT: To treat cancer effectively, patients must follow prescribed chemotherapy treatments without interruption, yet most cancer treatments produce side effects that devastate quality of life (e.g., nausea, vomiting, anorexia, weight loss). Although hundreds of thousands of patients undergo chemotherapies each year, the neural mechanisms mediating their side effects are unknown. The current data outline a neural circuit activated by cisplatin chemotherapy and demonstrate that glutamate signaling in the amygdala, arising from hindbrain projections, is required for the full expression of cisplatin-induced malaise, anorexia, and body weight loss. Together, these data help to characterize the neural circuits and neurotransmitters mediating chemotherapy-induced energy balance dysregulation, which will ultimately provide an opportunity for the development of well tolerated cancer and anti-emetic treatments.

Liujunanwei decoction attenuates cisplatin-induced nausea and vomiting in a Rat-Pica model partially mediated by modulating the gut micsrobiome.

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 via alteration of gut microbiota. We evaluated the effect of LJAW on cisplatin (DDP)-induced nausea and vomiting using a rat-pica model. Rats react to emetic-producing stimuli with increased kaolin consumption, a phenomenon called pica. The rats were injected with cisplatin and then randomly assigned to the control (DDP), Ondansetron or LJAW. The intake of kaolin and chow diet as well as body weights were recorded every 24 hours. Fecal samples were collected prior to, after three and seven days of treatment. The expression of proteins was measured by western blot. The concentration of cytokines and serotonin was evaluated using ELISA assay kits. Kaolin consumption in rats induced by cisplatin was reduced by 16.5%, 22.5%, and 30.1% in the LJAW group compared to the DDP group at 24 hours, 48 hours and 72 hours, respectively (p>0.05). LJAW significantly increased the food intake of the rats (13.94 ± 4.73 g) during the first 24 hours as opposed to the DDP (9.23 ± 3.77 g) (p<0.05). 16S rRNA gene sequencing showed the abundance of Bacteroidetes increased in cisplatin treated rats. In addition, cisplatin injection caused an enrichment of Escherichia-Shigella and Enterococcus at the genus level. While, enrichment of Blautia and Lactobacillus was presented in LJAW treated rats. Serotonin decreased in LJAW treated intestine and medulla oblongata tissues. Further, the protein expression of tryptophan hydroxylase 1 (TPH1) a rate limiting enzyme of serotonin was inhibited in LJAW treated rat's jejunum compared with cisplatin only treated rats. In addition, LJAW downregulated chemotherapy induced elevated inflammation. The results of this study indicated that LJAW is capable of decreasing cisplatin-induced kaolin intake in rat-nausea model (pica), which might be mediated through gut microbiome-induced anti-inflammation and anti-serotonin synthesis functions.

[6]-Gingerol Ameliorates Cisplatin-Induced Pica by Regulating the TPH/MAO-A/SERT/5-HT/5-HT3 Receptor System in Rats.

PURPOSE: [6]-gingerol is a bioactive compound extracted from ginger, a traditional anti-emetic herb in Chinese medicine. Previous studies have demonstrated that [6]-gingerol can ameliorate chemotherapy-induced pica in rats, although the underlying mechanism has not been elucidated. This study is designed to investigate [6]-gingerol's antiemetic mechanism focusing on the 5-hydroxytryptamine (serotonin, 5-HT) system by evaluating the synthesis, metabolism and reuptake of 5-HT, as well as the mechanism of 5-hydroxytryptamine type 3 receptor (5-HT3 receptor), in a cisplatin-induced pica model of rats. METHODS: Rats were randomly divided into control group (vehicle + saline, Con), [6]-gingerol control group (50 mg/kg [6]-gingerol + saline, G-con), ondansetron control group (2.6 mg/kg ondansetron + saline, O-con), cisplatin model group (vehicle + cisplatin, Model), ondansetron-treated group (2.6 mg/kg ondansetron + cisplatin, O-treated), high dosage of [6]-gingerol-treated group (100 mg/kg [6]-gingerol + cisplatin, GH-treated), and low dosage of [6]-gingerol-treated group (50 mg/kg [6]-gingerol + cisplatin, GL-treated). The rats were administered with [6]-gingerol, ondansetron, and vehicle (3% Tween-80) by gavage twice (7:00 AM and 7:00 PM). One hour after the first treatment (8:00 AM), rats in groups Model, O-treated, GH-treated and GL-treated were injected intraperitoneally (i.p.) with 6 mg/kg cisplatin, and the other groups were injected i.p. with saline of equal volume. The consumption of kaolin of the rats were measured. All the rats were anesthetized by i.p. injection of pentobarbital sodium at 24 h post-cisplatin. After blood samples were taken, medulla oblongata and ileum were removed. The levels of 5-HT and its metabolite 5-HIAA in ileum, medulla oblongata and serum were determined using high-performance liquid chromatography with electrochemical detection (HPLC-ECD). The mRNA expression levels of 5-HT3 receptor, tryptophan hydroxylase (TPH), monoamine oxidase A (MAO-A) and serotonin reuptake transporter (SERT) were detected by real-time PCR. The protein expression levels and distribution of 5-HT3 receptor, TPH and MAO-A in the medulla oblongata and ileum were measured by Western blotting and immunohistochemistry, respectively. RESULTS: [6]-gingerol treatment significantly reduced the kaolin ingestion and the increase in 5-HT concentration in rats induced by cisplatin. TPH, MAO-A, SERT, and 5-HT3 receptor are important in 5-HT metabolism, and cisplatin-induced alterations in the associated protein/mRNA levels were restored when treated with [6]-gingerol. CONCLUSION: This suggests that the antiemetic effect of [6]-gingerol against cisplatin-induced emesis may be due to 5-HT attenuation via modulating the TPH/MAO-A/SERT/5-HT/5-HT3 receptor system.

Chemotherapy-induced kaolin intake is increased by lesion of the lateral parabrachial nucleus of the rat.

Anticancer agents, such as cisplatin, stimulate nausea, vomiting, and behaviors indicative of malaise. Rats and mice do not possess a vomiting response, and, therefore, in these species, the ingestion of kaolin clay (a pica response) has been used as an index of malaise. In the rat, cisplatin-induced kaolin intake is inhibited by antiemetic treatments. In addition, cisplatin activates vagal afferent fibers in the gut, and kaolin intake induced by cisplatin is largely dependent on an intact vagus. Nevertheless, little is known about the brain pathways controlling pica. We investigated the role of the lateral parabrachial nucleus (lPBN), a major visceral afferent link between the hindbrain and forebrain, in cisplatin-induced c-Fos expression and pica. Injection of cisplatin (6 mg/kg ip) produced c-Fos expression in the ventrolateral (external) lPBN, a region receiving viscerosensory input. In rats with bilateral ibotenic acid lPBN lesions, cisplatin treatment substantially increased kaolin intake compared with controls ( approximately 30 g vs. approximately 5 g, respectively, over 24 h). Food intake was reduced by cisplatin treatment and by apomorphine, an emetic agent that acts centrally. Unlike cisplatin, however, apomorphine stimulated kaolin intake to a similar degree in both the lesioned and control rats, suggesting that lPBN damage neither produces nonspecific effects nor enhances malaise in general. These data suggest that lPBN-lesioned animals not only demonstrate pica after cisplatin treatment, but, in fact, show an exaggerated response that is greatly in excess of any treatment known to produce kaolin intake in rats.

Geochemical and mineralogical characteristics of elephant geophagic soils in Udawalawe National Park, Sri Lanka.

Geophagy or deliberate ingestion of soils was observed among Asian elephants (Elephas maximus) in the Udawalwe National Park, Sri Lanka, for several years. The geochemical and mineralogical composition of the clayey soil layers which are purposefully selected and eaten by elephants in the park were studied, in order to identify the possible reasons for elephant geophagy. The concentrations of major and trace elements were determined by means of X-ray fluorescence spectrometry in 21 soil samples from eight geophagic sites and six soil samples collected from four non-geophagic sites. The mineralogical composition of selected soil samples was investigated using X-ray diffractometry (XRD). These geochemical analyses revealed that geophagic soils in the study areas are deeply weathered and that most of the elements are leached from the soil layers under extreme weathering conditions. The XRD data showed that the soils of the area consisted mainly quartz, feldspar, and the clay minerals kaolinite, Fe-rich illite, and smectite. Although no significant geochemical differences were identified between geophagic and non-geophagic soils, a clear difference was observed in their clay mineralogical content. Soils eaten by elephants are richer in kaolinite and illite than non-geophagic soils, which contain a higher amount of smectite. It is suggested that elephants in Udawalawe National Park ingest soils mainly not to supplement the mineral contents of their forage but to detoxify unpalatable compounds in their diet.

Hypophagia induced by hindbrain serotonin is mediated through central GLP-1 signaling and involves 5-HT2C and 5-HT3 receptor activation.

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.

Hindbrain GLP-1 receptor mediation of cisplatin-induced anorexia and nausea.

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.

Potential energetic implications of emesis in the house musk shrew (Suncus murinus).

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.

Induction and antagonism of pica induced by teriparatide in rats.

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.

Detoxification and mineral supplementation as functions of geophagy.

Clays employed historically in the consumption of astringent acorns plus seven edible clays from Africa were examined in relation to the functional significance of human geophagy. On the basis of sorptive maxima for tannic acid ranging from 5.6 to 23.7 mg/g, we conclude that adsorption of tannic acid in traditional acorn preparation methods in California and Sardinia helped make these nuts palatable. Calcium available in solution at pH 2.0 and 0.1 mol NaCl/L was 2.10 and 0.71 mg/g for the Sardinian and Californian clays, respectively. The African clays released calcium, copper, iron, magnesium, manganese, or zinc in amounts of nutritional significance from some clays but not from others. A clay recovered from an archaeological site occupied by Homo erectus and early H. sapiens was indistinguishable mineralogically, in detoxification capacity and in available minerals, from clays used in Africa today. We suggest that the physiological significance of geophagy made it important in the evolution of human dietary behavior.

Pica and mineral status in the mentally retarded.

A study population consisting of 66 mentally retarded individuals, 60 with and six without pica, was evaluated for iron status, and for plasma and hair zinc, copper, and magnesium levels within a month of known dietary intake. The parameters were all within the normal range for individuals without pica. In contrast, subjects practicing pica had low plasma zinc and elevated plasma copper values as compared to those without pica. Plasma magnesium was in the low normal range for all individuals in the study population. Among the indicators of iron status measured, Hb, hematocrit, plasma iron, total iron-binding capacity, iron saturation, and plasma ferritin, several values were low (p less than 0.001). Depression in plasma zinc level was related to the type and severity of the pica. In plasma, zinc was positively correlated with iron and negatively correlated with copper. No relationships were found between dietary intakes and plasma levels of these minerals. The data suggest that malabsorption of zinc and iron were associated with some types of pica although the individuals received adequate dietary intake of minerals. Zinc, copper, and magnesium concentrations in hair were within normal ranges. Hair was a less sensitive indicator than plasma of trace element status.

Low levels of zinc in hair and blood, pica, anorexia, and poor growth in Chinese preschool children.

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.

Estimating soil ingestion: the use of tracer elements in estimating the amount of soil ingested by young children.

In this pilot study, we modified methods used in estimating the amount of soil ingested by ruminants to measure soil ingested by children. Using aluminum, silicon, and titanium as tracers, we estimated soil ingestion for 59 children aged 1-3 yr from East Helena, Montana. Estimated daily soil ingestion based on aluminum and silicon concentrations were 181 and 184 mg/day, respectively, whereas the estimate based on the titanium concentration was about 10 times higher, 1,834 mg/day. Although we do not consider these estimates accurate measures of soil ingestion, the method we used is a reasonable approach that, to our knowledge, has not been used before in humans. However, our estimates will be revised as refinement of this method and better understanding of the metabolism of aluminum, silicon, and titanium lead to more accurate data for analysis.

Involvement of substance P in the development of cisplatin-induced acute and delayed pica in rats.

BACKGROUND AND PURPOSE: Although substance P (SP) and neurokinin NK1 receptors have been reported to be involved in cisplatin-induced acute and delayed emesis, their precise roles remain unclear. Pica, the consumption of non-nutrient materials such as kaolin in rats, can be used as a model of nausea in humans. We investigated the time-dependent changes in cisplatin-induced pica and the involvement of SP and NK1 receptors in this behaviour. EXPERIMENTAL APPROACH: Rats were administered cisplatin with or without a daily injection of a 5-HT3 receptor antagonist (granisetron) or an NK1 receptor antagonist (aprepitant), and kaolin intake was then monitored for 5 days. The effects of granisetron on the cisplatin-induced expression of preprotachykinin-A (PPT-A) mRNA, which encodes mainly for SP, and on SP release in the medulla, measured by in vivo brain microdialysis, were also investigated. KEY RESULTS: Cisplatin induced pica within 8 h of its administration that continued for 5 days. Granisetron inhibited the acute phase (day 1), but not the delayed phase (days 2-5), of pica, whereas aprepitant abolished both phases. Within 24 h of the injection of cisplatin, PPT-A mRNA expression and SP release in the medulla were significantly increased; these findings lasted during the observation period and were inhibited by granisetron for up to 24 h. CONCLUSIONS AND IMPLICATIONS: The profiles of cisplatin-induced pica in rats are similar to clinical findings for cisplatin-induced emesis in humans, and we showed that SP production in the medulla and activation of NK1 receptors are involved in this cisplatin-induced pica.

Human geophagia, calabash chalk and undongo: mineral element nutritional implications.

The prime aim of our work is to report and comment on the bioaccessible concentrations - i.e., the soluble content of chemical elements in the gastrointestinal environment that is available for absorption - of a number of essential mineral nutrients and potentially harmful elements (PHEs) associated with the deliberate ingestion of African geophagical materials, namely Calabash chalk and Undongo. The pseudo-total concentrations of 13 mineral nutrients/PHEs were quantified following a nitric-perchloric acid digestion of nine different Calabash chalk samples, and bioaccessible contents of eight of these chemical elements were determined in simulated saliva/gastric and intestinal solutions obtained via use of the Fed ORganic Estimation human Simulation Test (FOREhST) in vitro procedure. The Calabash chalk pseudo-total content of the chemical elements is often below what may be regarded as average for soils/shales, and no concentration is excessively high. The in vitro leachate solutions had concentrations that were often lower than those of the blanks used in our experimental procedure, indicative of effective adsorption: lead, a PHE about which concern has been previously raised in connection with the consumption of Calabash chalk, was one such chemical element where this was evident. However, some concentrations in the leachate solutions are suggestive that Calabash chalk can be a source of chemical elements to humans in bioaccessible form, although generally the materials appear to be only a modest supplier: this applies even to iron, a mineral nutrient that has often been linked to the benefits of geophagia in previous academic literature. Our investigations indicate that at the reported rates of ingestion, Calabash chalk on the whole is not an important source of mineral nutrients or PHEs to humans. Similarly, although Undongo contains elevated pseudo-total concentrations of chromium and nickel, this soil is not a significant source to humans for any of the bioaccessible elements investigated.

A study on the effects of pica and iron-deficiency anemia on oxidative stress, antioxidant capacity and trace elements.

Pica is defined as developmentally inappropriate consumption of nonnutritive substances for at least 1 month. There are a few studies on serum trace element levels of patients with pica. The literature contains contracting data on the levels of oxidative stress and antioxidant levels in patients with iron-deficiency anemia (IDA). The effect of pica on oxidative stress and antioxidant capacity has not been investigated yet. The present study evaluated the effects of pica and IDA on oxidative stress and antioxidant capacity as well as on the levels of trace elements including serum zinc and selenium in 47 children with IDA plus pica, 22 children with IDA only and 21 nonanemic children as controls. The results demonstrated significantly lower levels of serum selenium and zinc in pica and IDA groups compared to the control group. Total oxidant levels were highest in the pica group and consistently, the lowest total antioxidant capacity was observed again in the pica group. Comparison of pica and IDA groups yielded significantly lower levels of total antioxidant levels and significantly higher oxidative stress index in the pica group. Consequently, it is thought that the detrimental effects of pica within the organism were mediated by adverse impacts on antioxidant capacity and oxidative stress. These effects should be kept in mind while managing patients with pica.

Levels of lead, arsenic, mercury and cadmium in clays for oral use on the Dutch market and estimation of associated risks.

Pregnant women in Africa, Asia and Suriname, and some immigrants in Western societies, traditionally consume clay products known by a variety of names such as mabele, calabash chalk, sikor and pimba. Furthermore, clay is used for health purposes in Western societies. Because certain clays can contain high levels of metals and metalloids, the aim of this study was to determine lead, arsenic, mercury and cadmium in clay products for oral use available on the Dutch market. Traditional clays originating from Africa (n = 10) and Suriname (n = 26), and health clays (n = 27) were sampled from 2004 up to and including 2012. Total metal and metalloid contents were measured by ICP-MS and showed maximum levels of lead, arsenic, mercury and cadmium of 99.7, 45.1, 2.2 and 0.75 mg kg⁻¹, respectively. In the absence of maximum limits for these type of clays, the potential exposure was estimated from the determined concentration, the estimated daily use level of the clays, and the estimated bioaccessibility of the different metals and arsenic. The intake estimates were compared with existing health-based guidance values. For lead, the use of 34 of the 36 traditional clays and two of the 27 health clays would result in intake levels exceeding the toxicological limit by up to 20-fold. Use of 15 of the 35 traditional clays and 11 of the 27 health clays would result in intake levels exceeding the toxicological limit for inorganic arsenic by up to 19-fold. Although limited bioaccessibility from the clay may limit the exposure and exceedance of the health-based guidance values, it was concluded that lead and arsenic intakes from some clay products could be of concern also because of their use by pregnant women and the potential developmental toxicity. As a result the use of these products, especially by pregnant women, should be discouraged.

Association of pica with anemia and gastrointestinal distress among pregnant women in Zanzibar, Tanzania.

The etiology of pica, the purposive consumption of non-food substances, is not understood, despite its ubiquity among gravidae. We examined correlates of pica in a representative obstetric population (n = 2,368) on Pemba Island, Zanzibar, Tanzania to examine proposed etiologies. Cross-sectional data were collected on socioeconomic characteristics, food intake, geophagy (earth consumption), amylophagy (raw starch consumption), anthropometry, iron status, parasitic burden, and gastrointestinal morbidities. Amylophagy was reported by 36.3%, geophagy by 5.2%, and any pica by 40.1%. There was a strong additive relationship of geophagy and amylophagy with lower hemoglobin (Hb) concentration and iron deficiency anemia. By multivariate logistic regression, any pica was associated with Hb level (odds ratio [OR] = 0.76, 95% confidence interval [CI] = 0.72-0.81), nausea (OR = 1.45, 95% CI = 1.20-1.73), and abdominal pain (OR = 1.22, 95% CI = 1.01-1.48). These striking results indicate that the nature of the relationship between pica, pregnancy, gastrointestinal distress, and iron deficiency anemia merits further investigation.