Development of a Digital Patient Assistant for the Management of Cyclic Vomiting Syndrome: Patient-Centric Design Study.

BACKGROUND: Cyclic vomiting syndrome (CVS) is an enigmatic and debilitating disorder of gut-brain interaction that is characterized by recurrent episodes of severe vomiting and nausea. It significantly impairs patients' quality of life and can lead to frequent medical visits and substantial health care costs. The diagnosis for CVS is often protracted and complex, primarily due to its exclusionary diagnosis nature and the lack of specific biomarkers. This typically leads to a considerable delay in accurate diagnosis, contributing to increased patient morbidity. Additionally, the absence of approved therapies for CVS worsens patient hardship and reflects the urgent need for innovative, patient-centric solutions to improve CVS management. OBJECTIVE: We aim to develop a digital patient assistant (DPA) for patients with CVS to address their unique needs, and iteratively enhance the technical features and user experience on the initial DPA versions. METHODS: The development of the DPA for CVS used a design thinking approach, prioritizing user needs. A literature review and Patient Advisory Board shaped the initial prototype, focusing on diagnostic support and symptom tracking. Iterative development, informed by the design thinking approach and feedback from patients with CVS and caregivers through interviews and smartphone testing, led to significant enhancements in user interaction and artificial intelligence integration. The final DPA's effectiveness was validated using the System Usability Scale and feedback questions, ensuring it met the specific needs of the CVS community. RESULTS: The DPA developed for CVS integrates an introductory bot, daily and weekly check-in bots, and a knowledge hub, all accessible via a patient dashboard. This multicomponent solution effectively addresses key unmet needs in CVS management: efficient symptom and impacts tracking, access to comprehensive disease information, and a digital health platform for disease management. Significant improvements, based on user feedback, include the implementation of artificial intelligence features like intent recognition and data syncing, enhancing the bot interaction and reducing the burden on patients. The inclusion of the knowledge hub provides educational resources, contributing to better disease understanding and management. The DPA achieved a System Usability Scale score of 80 out of 100, indicating high ease of use and relevance. Patient feedback highlighted the DPA's potential in disease management and suggested further applications, such as integration into health care provider recommendations for patients with suspected or confirmed CVS. This positive response underscores the DPA's role in enhancing patient engagement and disease management through a patient-centered digital solution. CONCLUSIONS: The development of this DPA for patients with CVS, via an iterative design thinking approach, offers a patient-centric solution for disease management. The DPA development framework may also serve to guide future patient digital support and research scenarios.

Anti-Emetics in Children Receiving Chemotherapy for Solid Tumors and Leukemia: Pharmacology and Optimization of Therapy for Nausea and Vomiting.

The management of chemotherapy-induced nausea and vomiting (CINV) in children remains challenging due to differences in the chemotherapy regimens, their relative emetogenicity compared to that in adults and differences in drug metabolism and the available formulations. The common four classes of anti-emetics used for the treatment and prophylaxis of CINV in children include dexamethasone, neurokinin-1 receptor antagonists, 5-hydroxytryptamine-3 receptor antagonists (5HT3RAs), and olanzapine. The appropriate dose of dexamethasone for CINV prophylaxis in children is unknown, with a significant variability in dosage ranging between 6 and 32 mg/m2/day. The dose of dexamethasone is decreased by 30% when this drug is combined with (fos)aprepitant in children, in contrast to a decrease of 50% required in adults. The use of aprepitant in younger children (<12 years) is often hampered by the non-availability of oral suspension formulations in many countries; alternatively, 80 mg capsules are administered for 1-3 days in certain institutes to children weighing between 15 and 40 kg. Among the different 5HT3RAs, palonosetron is comparatively metabolized faster in children than in adults, requiring a higher dosage for similar efficacy to that achieved in adults. Olanzapine is a newer agent, used in doses between 0.1 and 0.14 mg/kg/day in children, with good anti-emetic efficacy, but has sedation and hyperglycemia as concerning adverse effects. Drug interactions between anti-emetics and between anti-emetics and chemotherapy/supportive agents (azole antifungals, cyclosporine, arsenic trioxide), especially QTc prolongation, should be considered during prescription.

A poisonous cocktail: interplay of cereulide toxin and its structural isomers in emetic Bacillus cereus.

Food intoxications evoked by emetic Bacillus cereus strains constitute a serious threat to public health, leading to emesis and severe organ failure. The emetic peptide toxin cereulide, assembled by the non-ribosomal peptide synthetase CesNRPS, cannot be eradicated from contaminated food by usual hygienic measures due to its molecular size and structural stability. Next to cereulide, diverse chemical variants have been described recently that are produced concurrently with cereulide by CesNRPS. However, the contribution of these isocereulides to the actual toxicity of emetic B. cereus, which produces a cocktail of these toxins in a certain ratio, is still elusive. Since cereulide isoforms have already been detected in food remnants from foodborne outbreaks, we aimed to gain insights into the composition of isocereulides and their impact on the overall toxicity of emetic B. cereus. The amounts and ratios of cereulide and isocereulides were determined in B. cereus grown under standard laboratory conditions and in a contaminated sample of fried rice balls responsible for one of the most severe food outbreaks caused by emetic B. cereus in recent years. The ratios of variants were determined as robust, produced either under laboratory or natural, food-poisoning conditions. Examination of their actual toxicity in human epithelial HEp2-cells revealed that isocereulides A-N, although accounting for only 10% of the total cereulide toxins, were responsible for about 40% of the total cytotoxicity. An this despite the fact that some of the isocereulides were less cytotoxic than cereulide when tested individually for cytotoxicity. To estimate the additive, synergistic or antagonistic effects of the single variants, each cereulide variant was mixed with cereulide in a 1:9 and 1:1 binary blend, respectively, and tested on human cells. The results showed additive and synergistic impacts of single variants, highlighting the importance of including not only cereulide but also the isocereulides in routine food and clinical diagnostics to achieve a realistic toxicity evaluation of emetic B. cereus in contaminated food as well as in patient samples linked to foodborne outbreaks. Since the individual isoforms confer different cell toxicity both alone and in association with cereulide, further investigations are needed to fully understand their cocktail effect.

Universal and Naked-Eye Diagnostic Platform for Emetic Bacillus cereus Based on RPA-Assisted CRISPR/Cas12a.

Emetic Bacillus cereus (B. cereus), which can cause emetic food poisoning and in some cases even fulminant liver failure and death, has aroused widespread concern. Herein, a universal and naked-eye diagnostic platform for emetic B. cereus based on recombinase polymerase amplification (RPA)-assisted CRISPR/Cas12a was developed by targeting the cereulide synthetase biosynthetic gene (cesB). The diagnostic platform enabled one-pot detection by adding components at the bottom and cap of the tube separately. The visual limit of detection of RPA-CRISPR/Cas12a for gDNA and cells of emetic B. cereus was 10-2 ng µL-1 and 102 CFU mL-1, respectively. Meanwhile, it maintained the same sensitivity in the rice, milk, and cooked meat samples even if the gDNA was extracted by simple boiling. The whole detection process can be finished within 40 min, and the single cell of emetic B. cereus was able to be recognized through enrichment for 2-5 h. The good specificity, high sensitivity, rapidity, and simplicity of the RPA-assisted CRISPR/Cas12a diagnostic platform made it serve as a potential tool for the on-site detection of emetic B. cereus in food matrices. In addition, the RPA-assisted CRISPR/Cas12a assay is the first application in emetic B. cereus detection.

Analysis of Microbial Composition of Edible Insect Products Available for Human Consumption within the United States Using Traditional Microbiological Methods and Whole Genome Sequencing.

Edible insects offer a promising protein source for humans, but their food safety risks have not been previously investigated within the United States. Therefore, the aim of this study was to investigate the microbial content of processed edible insect products. A total of eight different types of edible insect products, including diving beetles, silkworms, grasshoppers, Jamaican crickets, mealworms, mole crickets, whole roasted crickets, and 100% pure cricket powder, were purchased from a large online retailer for the analysis. All the products were purchased in August 2022 and examined between August 2022 and November 2022. Traditional microbiological methods were employed to determine microbial counts for each product type using three replicates (total number of samples = 24). This included assessing aerobic bacterial spore, lactic acid bacteria, Enterobacteriaceae, total viable counts, and the presence of Salmonella. Additionally, whole genome sequencing was employed to further characterize selected colonies (n = 96). Microbial counts data were statistically analyzed using one-way ANOVA, while sequence data were taxonomically classified using Sepia.Bacilluscereusgroup isolates underwent additional characterization with Btyper3. Product type significantly influenced total viable counts, bacterial spore counts, and lactic acid bacteria counts (P = 0.00391, P = 0.0065, and P < 0.001, respectively), with counts ranging from < 1.70 to 6.01 Log10 CFU/g, <1.70 to 5.25 Log10 CFU/g, and < 1.70 to 4.86 Log10 CFU/g, respectively. Enterobacteriaceae were only detected in mole crickets (<2.30 Log10 CFU/g) and house cricket powder (<2.15 Log10 CFU/g). All samples were negative for Salmonella. Whole genome sequencing revealed the presence of 12 different bacterial genera among the analyzed isolates, with a majority belonging to the Bacillus genus. Some of the isolates of Bacillus cereus group were identified as biovar Emeticus. Overall, although edible insects offer a promising food alternative, the presence of Bacillus cereus group in some products could raise concerns regarding food safety.

Medical management of pneumoperitoneum, gastric pneumatosis, and hepatic venous gas secondary to 3% hydrogen peroxide toxicity in a dog.

OBJECTIVE: To describe the medical management and outcome of a dog suffering severe hydrogen peroxide toxicity. CASE SUMMARY: A 3-year-old neutered female Bichon Frise was presented to an emergency and referral practice after ingestion of 10-20 mL/kg 3% hydrogen peroxide. On presentation, the dog was obtunded, was tachypneic, and had severe gastric tympany. Abdominal radiographs revealed pneumoperitoneum, gastric pneumatosis, and hepatic venous gas. The dog was managed conservatively with supportive care and oxygen therapy. Repeat radiographs 6 hours later showed complete resolution of all gas inclusions. While hospitalized, the dog developed severe hematemesis, and abdominal ultrasound revealed severe gastric wall thickening. Subsequent endoscopy confirmed severe gastric mucosal necrosis without evidence of deeper ulceration and relatively mild petechiation of the esophagus. The dog was ultimately discharged after 5 days of hospitalization and continued to do well at home. Recheck ultrasound 5 weeks postdischarge showed normal gastric wall appearance. NEW OR UNIQUE INFORMATION PROVIDED: To the authors' knowledge, this is the first reported case of pneumoperitoneum secondary to hydrogen peroxide toxicity and the first description of the clinical course of severe toxicity in dogs.

Toxigenic diversity of Bacillus cereus isolated from fresh produce and effects of various factors on the growth and the cytotoxicity of B. cereus.

This study analyzed the virulence, growth characteristics, and cytotoxicity of Bacillus cereus strains isolated from fresh produce, including romaine lettuce, sesame leaf, tomato, and cucumber grown by different methods. Polymerase chain reaction (PCR) was used to assess the toxigenic potential, and the cytotoxicity of B. cereus was estimated using cell-free supernatant in HEp-2 cells. The study found that hblD was the predominant diarrheal enterotoxin in the 59 isolated B. cereus strains, followed by nheB and hblC. The optimal temperatures for growth ranged from 42 to 44 °C, with the highest growth rates and shortest lag times. Cytotoxicity varied greatly depending on abiotic factors, including NaCl, pH, and medium, and was not always correlated with cell population. The study highlights the importance of establishing control measures to prevent B. cereus intoxication in fresh vegetables. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01330-0.

Jelly snakes to reduce early postoperative vomiting in children after adenotonsillectomy: The randomized controlled snakes trial.

BACKGROUND: Despite the use of dual antiemetic agents, postoperative nausea and vomiting (PONV) occurs in an unacceptably large number of patients post-tonsillectomy. There has been increased interest in alternative and non-pharmacological treatments for PONV e.g., chewing gum. We investigated if chewing a large confectionary jelly snake had prophylactic antiemetic effects postoperatively in young children. METHODS: Prospective, open-label randomised controlled trial of 240 patients, 2-16 years. Patients administered a confectionary jelly snake to chew postoperatively were compared with a control group. The primary outcome was the number of episodes of vomiting within 6 h of the operation on an intention-to-treat basis. SECONDARY OUTCOMES: incidence of nausea, vomiting at 6 and 24 h, rescue antiemetic use, acceptability, delayed discharge. RESULTS: 233 patients were randomised to receive the confectionary snake (snake group, 118) or standard care (control group, 115). The number of vomiting episodes in 6 h was similar between groups on an intention-to-treat basis, with 39 episodes across 22 (19%) patients in the control group and 31 across 19 (16%) patients in the snake group (p = 0.666). From post anaesthetic care unit until 24 h there was no difference in doses of antiemetics or delayed discharge due to PONV. A secondary as per protocol analysis did not change this result. CONCLUSIONS: Chewing of confectionery jelly snakes within one hour of waking following adenotonsillectomy with vapour-maintained anaesthesia and two prophylactic antiemetics did not further reduce the incidence of early vomiting. REGISTRATION: prospective registration at the Australia and New Zealand Clinical Trials Registry (ACTRN12618000637246).

The potential of lactose to inhibit cereulide biosynthesis of emetic Bacillus cereus in milk.

This study aims to investigate the potential role of lactose on cereulide biosynthesis by emetic Bacillus cereus in dairy matrices. The cereulide yields in whole milk and lactose-free milk were investigated using the emetic reference strain F4810/72. To eliminate the influence of complex food substrates, the LB medium model was further used to characterize the effect of lactose on cereulide produced by F4810/72 and five other emetic B. cereus strains. Results showed that the lactose-free milk displayed a 13-fold higher amount of cereulide than whole milk, but the cereulide level could be reduced by 91 % when the lactose content was restored. The significant inhibition of lactose on cereulide yields of all tested B. cereus strains was observed in LB medium, showing a dose-dependent manner with inhibition rates ranging of 89-98 %. The growth curves and lactose utilization patterns of all strains demonstrated that B. cereus cannot utilize lactose as a carbon source and lactose might act as a signal molecule to regulate cereulide production. Moreover, lactose strongly repressed the expression of cereulide synthetase genes (ces), possibly by inhibiting the key regulator Spo0A at the transcriptional level. Our findings highlight the potential of lactose as an effective strategy to control cereulide production in food.

2023 updated MASCC/ESMO consensus recommendations: prevention of nausea and vomiting following high-emetic-risk antineoplastic agents.

PURPOSE: This systematic review updates the MASCC/ESMO recommendations for high-emetic-risk chemotherapy (HEC) published in 2016-2017. HEC still includes cisplatin, carmustine, dacarbazine, mechlorethamine, streptozocin, and cyclophosphamide in doses of > 1500 mg/m2 and the combination of cyclophosphamide and an anthracycline (AC) in women with breast cancer. METHODS: A systematic review report following the PRISMA guidelines of the literature from January 1, 2015, until February 1, 2023, was performed. PubMed (Ovid), Scopus (Google), and the Cochrane Database of Systematic Reviews were searched. The literature search was limited to randomized controlled trials, systematic reviews, and meta-analyses. RESULTS: Forty-six new references were determined to be relevant. The main topics identified were (1) steroid-sparing regimens, (2) olanzapine-containing regimens, and (3) other issues such as comparisons of antiemetics of the same drug class, intravenous NK1 receptor antagonists, and potentially new antiemetics. Five updated recommendations are presented. CONCLUSION: There is no need to prescribe steroids (dexamethasone) beyond day 1 after AC HEC, whereas a 4-day regimen is recommended in non-AC HEC. Olanzapine is now recommended as a fixed part of a four-drug prophylactic antiemetic regimen in both non-AC and AC HEC. No major differences between 5-HT3 receptor antagonists or between NK1 receptor antagonists were identified. No new antiemetic agents qualified for inclusion in the updated recommendations.

Characterization of the Toxigenic Potential of Bacillus cereus sensu lato Isolated from Raw Berries and Their Products.

Bacillus cereus is estimated to be responsible for 1.4-12% of all food poisoning outbreaks worldwide. The objective of this study was to investigate the toxigenic potential of 181 isolates of B. cereus previously recovered from different types of berries and berry products (strawberries, raspberries, blackberries, and blueberries) by assessing the presence of enterotoxin genes (hblA, hblC, hblD, nheA, nheB, nheC, and cytK) and an emetic toxin cereulide synthetase gene (ces). The cytotoxic activity on Caco-2 cells was also evaluated for the two isolates containing the gene cytK. Twenty-three toxigenic profiles were found. The nheABC (91.7%) and hblACD (89.0%) complexes were the most prevalent among the isolates, while the cytK and ces genes were detected in low percentages, 1.1% and 3.3%, respectively. In addition, the nheABC/hblACD complex and ces genes were detected in isolates recovered throughout the production process of blackberries and strawberries. The cytotoxic activity on Caco-2 cells was also observed to be greater than 60% for isolates containing the cytK gene.

Severe acute drug-induced dystonia in the post-operative period requiring tracheal re-intubation.

Ondansetron is a highly selective 5-hydroxytryptamine receptor antagonist and the most commonly used anti-emetic for the prevention of postoperative nausea and vomiting. Ondansetron has a low affinity for dopamine receptors and so extrapyramidal side effects are rare. Here, we present the case of a 14-year-old girl who developed a severe post-operative acute dystonic reaction which included oculogyric crisis. We believe that ondansetron was the most likely cause, although propofol may have been a synergistic or alternative causative agent. The patient had no significant past medical history and had previously undergone two uneventful general anaesthetics which included both ondansetron and propofol. The prolonged duration and severity of the reaction and failure to fully respond to specific treatments resulted in the need for tracheal intubation and transfer to a paediatric intensive care unit. She subsequently recovered uneventfully with no ongoing neurological sequalae. Ondansetron-induced dystonic reactions are rare and unpredictable and can occur in patients who have previously received the drug without complication. They are thought to be caused by an imbalance between inhibitory and excitatory neurotransmitters in the extrapyramidal system. Specific treatments include anticholinergics, antihistamines and benzodiazepines.

A re-consideration of neural/receptor mechanisms in chemotherapy-induced nausea and vomiting: current scenario and future perspective.

The neural mechanisms and the receptors behind the course of chemotherapy-induced nausea and vomiting (CINV) are well described and considered mechanistically multifactorial, whereas the neurobiology of nausea is not completely understood yet. Some of the anti-neoplastic medications like cisplatin result in biphasic vomiting response. The acute phase of vomiting is triggered mainly via the release of serotonin from the enterochromaffin (EC) cells in the gastrointestinal tract (GIT) and results in stimulation of dorsal vagal complex (DVC) of the vomiting center and the vomiting is initiated by downward communication to the gut via vagal efferents. Agonism of 5HT3 receptors is majorly involved in the mediation of the acute phase. Therefore, antagonists at 5HT3 receptors are effective in the management of acute-phase vomiting episodes. Likewise, Dopamine type 2 (D2) receptors, dopamine neurotransmitter, Muscarinic receptors (M3), GLP1 receptors, and histaminergic receptors (H1) are also implicated in the vomiting act as well. In continuation, Cannabinoid type 1 (CB1) receptors are also recommended and included in the guidelines as agonism of presynaptically located CB1 receptors inhibits the release of excitatory neurotransmitters responsible for vomiting initiation. The delayed phase involves the release of "Substance P" in the gut and results in the stimulation of neurokinin-1 (NK1) receptors centrally in the area postrema (AP) and nucleus tractus solitarius (NTS), subsequently the vomiting response. The current understanding is the existence of overlapping mechanisms of neurotransmitters, serotonin, dopamine, and substance P throughout the time course of CINV. Furthermore, the emetic neurotransmitters are released via calcium ion (Ca++)-dependent mechanisms, implicating the molecular targets of intracellular Ca++ signaling in emetic circuitry. The current review entails the neurobiology of nausea and vomiting induced by cancer chemotherapeutic agents and the recent approaches in the management.

Stability and emetic activity of enterotoxin like X (SElX) with high carrier rate of food poisoning Staphylococcus aureus.

In order to analyze and clarify the thermal stability of food poisoning Staphylococcus aureus (S. aureus) enterotoxin-like X (SElX) and the biological characteristics of digestive enzymes, and to evaluate the risk of S. aureus carrying selx gene in food poisoning, the selx gene carrying rates of 165 strains isolated from 95 food poisoning events from 2006 to 2019 were first statistically analyzed. Subsequently, the purified recombinant SElX protein was digested and heated, and the superantigen activity was verified with mouse spleen cells and peripheral blood mononuclear cells of kittens. At the same time, the emetic activity and toxicity of SElX were evaluated using the kitten vomiting animal model, mice toxin model and in vitro cell models. The results showed the selx gene carrying rate of 165 food poisoning S. aureus strains was 90.30 %. SElX had significant resistance to heat treatment and pepsin digestion (pH = 4.0 and pH = 4.5), and had good superantigen activity and emetic activity. However, there is no significant lethal effect on mice and no significant toxicity to cells. Importantly, we found that SElX had an inhibitory effect on acidic mucus of goblet cells in various segments of the small intestine. The present study investigated the stability of SElX, and confirmed the emetic activity of SElX by establishing a kitten vomiting model for the first time, suggesting that SElX is a high risk toxin of food poisoning, which will provide new ideas for the prevention and control of S. aureus food poisoning.

Susceptibility of emetic and enterotoxigenic Bacillus cereus grown at high temperature to disinfectants.

The prevalence of emetic strains in food products is rare; however, infection with these may be fatal to the vulnerable population. Bacterial control of the emetic Bacillus cereus strains is still unclear. This study aimed to assess the influence of high temperature on the disinfection of emetic and enterotoxigenic B. cereus. Emetic B. cereus strains survived up to 50 °C; the lag time and maximum growth rate were higher at 42 °C than those at 30 °C. Compared to enterotoxigenic B. cereus, all emetic food strains showed higher minimum inhibitory concentrations and minimum bactericidal concentrations for sodium hypochlorite and citric acid. The disinfectant susceptibility of the emetic B. cereus OS-05 strain incubated at a higher temperature did not increase and was maintained at the highest MBC value. In all emetic B. cereus strains, enterotoxin gene expression was upregulated at 42 °C and 45 °C. Increased ces gene expression was also found in emetic B. cereus strains GP-15 and OS-05, with upregulation of 128- and 820-fold at 42 °C. Thus, emetic B. cereus grown at high temperatures may resist common disinfectants of the food industry. The findings may help control B. cereus in food or the food processing industry.

Dimethyl sulfoxide favors the emetic efficacy of lycorine in beagle dogs - a novel strategy for the treatment of poisoning.

Poisoning in small animals represents an ongoing hazard and therapeutic problem in veterinary medicine. Therapeutic induction of emesis in time enables a fast elimination of a toxic compound resulting in a shortened course of poisoning and a higher safety level thereafter, which decisively improves prognosis and treatment. Lycorine is a reliable emetic drug in beagle dogs without serious side effects thought to be more beneficial in tolerability and efficacy than the rarely used apomorphine. Therefore, this study investigates efficacy and tolerability of differently composed potential drug formulations of lycorine hydrochloride for s.c. administration in dogs as an emetic principle. By emesis response analysis four dimethyl sulfoxide (DMSO)-based active pharmaceutical ingredient (API) formulations were favored. Two of them (F5 and F6) qualified for further drug development. Both formulations ensure a safe pharmacologically induced emesis within about 30 min after injection, suitable for use as an in time decontaminant in acute poisoning of dogs. DMSO-based formulations were well tolerated and offer a novel promising strategy for treatment of poisoning.

Pharmacokinetics of intramuscular maropitant in pigs (Sus scrofa domesticus).

Pigs are at risk of vomiting from medical conditions as well as the emetic side effects of drugs administered for peri-operative manipulations, but there is a lack of pharmacokinetic data for potential anti-emetic therapies, such as maropitant, in this species. The main objective of this study was to estimate plasma pharmacokinetic parameters for maropitant in pigs after a single intramuscular (IM) administration dosed at 1.0 mg/kg. A secondary objective was to estimate pilot pharmacokinetic parameters in pigs after oral (PO) administration at 2.0 mg/kg. Maropitant was administered to six commercial pigs at a dose of 1.0 mg/kg IM. Plasma samples were collected over 72 h. After a 7-day washout period, two pigs were administered maropitant at a dose of 2.0 mg/kg PO. Maropitant concentrations were measured via liquid chromatography/mass spectrometry (LC-MS/MS). A non-compartmental analysis was used to derive pharmacokinetics parameters. No adverse events were noted in any of the study pigs after administration. Following single IM administration, maximum plasma concentration was estimated at 412.7 ± 132.0 ng/mL and time to maximum concentration ranged from 0.083 to 1.0 h. Elimination half-life was estimated at 6.7 ± 1.28 h, and mean residence time was 6.1 ± 1.2 h. Volume of distribution after IM administration was 15.9 L/kg. Area under the curve was 1336 ± 132.0 h*ng/mL. The relative bioavailability of PO administration was noted to be 15.5% and 27.2% in the two pilot pigs. The maximum systemic concentration observed in the study pigs after IM administration was higher than what was observed after subcutaneous administration in dogs, cats, or rabbits. The achieved maximum concentration exceeded the concentrations for anti-emetic purposes in dogs and cats; however, a specific anti-emetic concentration is currently not known for pigs. Further research is needed into the pharmacodynamics of maropitant in pigs to determine specific therapeutic strategies for this drug.

Emetic Tartar-Loaded Liposomes as a New Strategy for Leishmaniasis Treatment.

Emetic tartar (ET), was used in the treatment of leishmaniasis but its use was discontinued due to its low therapeutic index. Liposomes have been shown to be a promising strategy for delivery of bioactive substances in the region of interest, in order to reduce and/or eliminate undesirable effects. In the present study, liposomes containing ET were prepared and characterized to evaluate acute toxicity as well as their leishmanicidal action using BALB/c mice with an inoculum of Leishmania (Leishmania) infantum. Liposomes were composed of egg phosphatidylcholine and 3ß-[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol, with an average diameter of 200 nm, zeta potential of +18 mV, and ET encapsulated into liposomes at a concentration near 2 g/L. Healthy mice were treated with ET or liposome containing ET (Lip-ET) in a single dose of 16 mg/kg of Sb3+ intravenously and observed for 14 days. The death of two animals in the ET-treated group and no deaths in the Lip-ET-treated group was observed. Higher hepatic and cardiac toxicity were observed in animals treated with ET when compared to animals treated with Lip-ET, blank liposomes (Blank-Lip) and PBS. The study of antileishmanial efficacy was conducted by intraperitoneal administration of Lip-ET, for ten consecutive days. It was observed by limiting dilution that treatments with liposomal formulations containing ET, as well as Glucantime®, led to a significant reduction in parasitic load in spleen and liver (p < 0.05) when compared to the untreated control group.

Oxaliplatin-Induced Damage to the Gastric Innervation: Role in Nausea and 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.