Investigation of EM Emissions by the Electrodynamic Tether, Inclusive of an Observational Program (EMET)

NASA Technical Reports Server (NTRS)

Estes, Robert D.

1998-01-01

Our TSS-1/R investigation, which we shall refer to as EMET in this report, was an integral part of the effort by the TSS-1/R Investigators' Working Group (IWG) to come to an understanding of the complex interaction between the tethered satellite system and the ionosphere. All of the space-borne experiments were designed to collect data relevant to the local interaction. Only the ground- based experiments, EMET and its Italian counterpart Observations on the Earth's Surface of Electromagnetic Emissions (OESEE), held out any hope of characterizing the long range effects of the interaction. This was to be done by detecting electromagnetic waves generated by the system in the ionosphere, assuming the signal reached the Earth's surface with sufficient amplitude. As the type of plasma waves excited to carry charge away from the charge-exchange regions of the system at each end of the tether is one of the theoretical points about which there is greatest disagreement, a definitive identification of tether-generated waves could mark significant progress in the so-called current closure problem of electrodynamic tethers. Dr. Mario Grossi of the Smithsonian Astrophysical Observatory (SAO) initiated the investigation, and his experience in the field of ULF-ELF waves and their detection was invaluable throughout its course. Rice University had the responsibility of setting up the EMET ULF-VLF ground stations under a subcontract from SAO. Principal Investigator (PI) for the Rice effort was Prof. William E. Gordon, who was primary observer at the Arecibo Observatory during TSS-LR. Dr. Steve Noble handled major day-to-day operations, training, and planning for the ground-based measurements. Dr. James McCoy of NASA JSC, a member of the Mona/Arecibo team, was pilot for the numerous flights ferrying personnel and equipment between Puerto Rico and Mona Island. Final responsibility for the measurements rested with SAO, and the activities of field personnel and SAO investigators were

Emetic Bacillus cereus Are More Volatile Than Thought: Recent Foodborne Outbreaks and Prevalence Studies in Bavaria (2007–2013)

PubMed Central

Blöchinger, Claudia; Zucker, Renate; Kämpf, Peter

2014-01-01

Several Bacillus cereus strains possess the genetic fittings to produce two different types of toxins, the heat-stable cereulide or different heat-labile proteins with enterotoxigenic potential. Unlike the diarrheal toxins, cereulide is (pre-)formed in food and can cause foodborne intoxications shortly after ingestion of contaminated food. Based on the widely self-limiting character of cereulide intoxications and rarely performed differential diagnostic in routine laboratories, the real incidence is largely unknown. Therefore, during a 7-year period about 4.300 food samples linked to foodborne illness with a preliminary report of vomiting as well as food analysed in the context of monitoring programs were investigated to determine the prevalence of emetic B. cereus in food environments. In addition, a lux-based real-time monitoring system was employed to assess the significance of the detection of emetic strains in different food matrices and to determine the actual risk of cereulide toxin production in different types of food. This comprehensive study showed that emetic strains are much more volatile than previously thought. Our survey highlights the importance and need of novel strategies to move from the currently taxonomic-driven diagnostic to more risk orientated diagnostics to improve food and consumer safety. PMID:24895578

Concentrations of Arsenic and Boron in Water, Sediment and the Tissues of Fish in Emet Stream (Turkey).

PubMed

Benzer, Semra

2017-06-01

In this study, the concentrations of arsenic and boron were determined in the water and the sediment, as well as in the muscle tissues of Squalius cephalus, Alburnoides bipunctatus, Barbus plebejus and Capoeta tinca from Emet Stream. The fish samples were caught in May 2011 and September 2012. The metal concentrations in the water samples were as follows: arsenic was 137.1-1002 µg L -1 , and boron was 2421-14490 µg L -1 . The metal concentrations in the sediment samples were as follows: arsenic was 14.51-3317.1 mg kg -1 , and boron was 14.22-1014.01 mg kg -1 . The mean tissue concentration of arsenic was lower than the TFC and WHO limits. Boron has been identified in fish tissues at concentrations between 0.26 and 2.96 mg kg -1 . The bioaccumulation in the muscle tissues of all fish species caught from Emet Stream did not exceed the limit values.

Delineation of vagal emetic pathways: intragastric copper sulfate-induced emesis and viral tract tracing in musk shrews

PubMed Central

Meyers, Kelly; Lim, Audrey; Dye, Matthew; Pak, Diana; Rinaman, Linda; Yates, Bill J.

2014-01-01

Signals from the vestibular system, area postrema, and forebrain elicit nausea and vomiting, but gastrointestinal (GI) vagal afferent input arguably plays the most prominent role in defense against food poisoning. It is difficult to determine the contribution of GI vagal afferent input on emesis because various agents (e.g., chemotherapy) often act on multiple sensory pathways. Intragastric copper sulfate (CuSO4) potentially provides a specific vagal emetic stimulus, but its actions are not well defined in musk shrews (Suncus murinus), a primary small animal model used to study emesis. The aims of the current study were 1) to investigate the effects of subdiaphragmatic vagotomy on CuSO4-induced emesis and 2) to conduct preliminary transneuronal tracing of the GI-brain pathways in musk shrews. Vagotomy failed to inhibit the number of emetic episodes produced by optimal emetic doses of CuSO4 (60 and 120 mg/kg ig), but the effects of lower doses were dependent on an intact vagus (20 and 40 mg/kg). Vagotomy also failed to affect emesis produced by motion (1 Hz, 10 min) or nicotine administration (5 mg/kg sc). Anterograde transport of the H129 strain of herpes simplex virus-1 from the ventral stomach wall identified the following brain regions as receiving inputs from vagal afferents: the nucleus of the solitary tract, area postrema, and lateral parabrachial nucleus. These data indicate that the contribution of vagal pathways to intragastric CuSO4-induced emesis is dose dependent in musk shrews. Furthermore, the current neural tracing data suggest brain stem anatomical circuits that are activated by GI signaling in the musk shrew. PMID:24430885

Comparison of palanosetron, granisetron and ondansetron as anti-emetics for prevention of postoperative nausea and vomiting in patients undergoing middle ear surgery.

PubMed

Basu, Anjana; Saha, Debdas; Hembrom, Bani P; Roy, Amit; Naaz, Anjum

2011-05-01

The objective of the study was to compare the efficacy of palanosetron (0.25 mg), granisetron (3.0 mg) and ondansetron (8.0 mg) used as anti-emetics for the prevention of postoperative nausea/vomiting in patients undergoing middle ear surgery. The study was done among 75 adult patients (age group 30-45 years) of which 50 were males and rest (25) females, all of ASA I and ASA II. The patients were randomly allocated into 3 equal groups: Group I (n = 25) received injection palanosetron (0.25 mg) IV, group II (n = 25) received injection granisetron (3 mg) IV and group III (n = 25) received injection ondansetron (8.0 mg) IV at the end of the surgical procedure. A standard general anaesthesia technique was employed. Emetic episodes and safety assessments were performed during two periods of 0-6 hours in the postanaesthesia care unit and 6-24 hours in the ward after anaesthesia. The incidence of emesis-free patients during the 0-6 hours period was 100% for group I; 72% for group II and 56% for group III. During the 6-24 hours period incidence of emesis-free patients were 96% for group I; 56% for group II and 32% for group III. So to conclude, a single dose of palanosetron (0.25 mg) is a superior anti-emetic to granisetron (3.0 mg) or ondansetron (8.0 mg) in complete prevention of postoperative nausea and vomiting after middle ear surgery during the first 24 hours period.

Comparison of Anorectic and Emetic Potencies of Deoxynivalenol (Vomitoxin) to the Plant Metabolite Deoxynivalenol-3-Glucoside and Synthetic Deoxynivalenol Derivatives EN139528 and EN139544

PubMed Central

Wu, Wenda; Zhou, Hui-Ren; Bursian, Steven J.; Pan, Xiao; Link, Jane E.; Berthiller, Franz; Adam, Gerhard; Krantis, Anthony; Durst, Tony; Pestka, James J.

2014-01-01

The mycotoxin deoxynivalenol (DON) elicits robust anorectic and emetic effects in several animal species. However, less is known about the potential for naturally occurring and synthetic congeners of this trichothecene to cause analogous responses. Here we tested the hypothesis that alterations in DON structure found in the plant metabolite deoxynivalenol-3-glucoside (D3G) and two pharmacologically active synthetic DON derivatives, EN139528 and EN139544, differentially impact their potential to evoke food refusal and emesis. In a nocturnal mouse food consumption model, oral administration with DON, D3G, EN139528, or EN139544 at doses from 2.5 to 10 mg/kg BW induced anorectic responses that lasted up to 16, 6, 6, and 3 h, respectively. Anorectic potency rank orders were EN139544>DON>EN139528>D3G from 0 to 0.5 h but DON>D3G>EN139528>EN139544 from 0 to 3 h. Oral exposure to each of the four compounds at a common dose (2.5 mg/kg BW) stimulated plasma elevations of the gut satiety peptides cholecystokinin and to a lesser extent, peptide YY3–36 that corresponded to reduced food consumption. In a mink emesis model, oral administration of increasing doses of the congeners differentially induced emesis, causing marked decreases in latency to emesis with corresponding increases in both the duration and number of emetic events. The minimum emetic doses for DON, EN139528, D3G, and EN139544 were 0.05, 0.5, 2, and 5 mg/kg BW, respectively. Taken together, the results suggest that although all three DON congeners elicited anorectic responses that mimicked DON over a narrow dose range, they were markedly less potent than the parent mycotoxin at inducing emesis. PMID:25173790

Development, validity and reliability testing of the East Midlands Evaluation Tool (EMET) for measuring impacts on trainees' confidence and competence following end of life care training.

PubMed

Whittaker, B; Parry, R; Bird, L; Watson, S; Faull, C

2017-02-02

To develop, test and validate a versatile questionnaire, the East Midlands Evaluation Tool (EMET), for measuring effects of end of life care training events on trainees' self-reported confidence and competence. A paper-based questionnaire was designed on the basis of the English Department of Health's core competences for end of life care, with sections for completion pretraining, immediately post-training and also for longer term follow-up. Preliminary versions were field tested at 55 training events delivered by 13 organisations to 1793 trainees working in diverse health and social care backgrounds. Iterative rounds of development aimed to maximise relevance to events and trainees. Internal consistency was assessed by calculating interitem correlations on questionnaire responses during field testing. Content validity was assessed via qualitative content analysis of (1) responses to questionnaires completed by field tester trainers and (2) field notes from a workshop with a separate cohort of experienced trainers. Test-retest reliability was assessed via repeat administration to a cohort of student nurses. The EMET comprises 27 items with Likert-scaled responses supplemented with questions seeking free-text responses. It measures changes in self-assessed confidence and competence on 5 subscales: communication skills; assessment and care planning; symptom management; advance care planning; overarching values and knowledge. Test-retest reliability was found to be good, as was internal consistency: the questions successfully assess different aspects of the same underlying concept. The EMET provides a time-efficient, reliable and flexible means of evaluating effects of training on self-reported confidence and competence in the key elements of end of life care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

A Clinico-analytical Study on Seed of Wrightia antidysenterica Linn. as a Therapeutic Emetic Agent (Vamaka Yoga) in the Management of Psoriasis.

PubMed

Bhattacharyya, Nirupam; Pujar, Muralidhar P; Chaturvedi, Ashutosh; Kumar, M Ashvini; Lohith, B A; Kumar, K N Sunil

2016-03-01

Wrightia antidysenterica Linn. (WA) is male variety Kutaja stated to be potent therapeutic emetic agent in skin disorders. Expulsion of doshas through oral route is termed as Vamana Karma (VK) (therapeutic emesis). However, so far, its utility for Vamana is not explored in detail, therefore there is a need to revalidate the utility of WA for Vamana. Hence, the above study was conducted to ascertain the efficacy as a therapeutic emetic agent (vamaka yoga) in the management of psoriasis along with quality control and standardization of this herb. The drug was standardized as per analytical procedures in Pharmacopeias. Thirty patients of psoriasis fulfilling inclusion criteria were taken for the study and Vamana with WA was conducted. Criteria were prepared to assess the signs and Symptoms of psoriasis. VK was assessed using the classical Lakshanas (features) such as Anthiki shudhi (Ending symptoms of emesis), Vaigiki shudhi (features of vomiting bouts), Maniki shudhi (Quantitative and qualitative purification), complications. VK with WA showed significant relief in parameters of psoriasis such as scaling, itching, candle grease sign (P < 0.001), and psoriasis area and severity index score (P = 0.001). In VK with WA, mean number of Vegas (vomiting bouts) was 6.91. 66% patients showing quantitative purification between 301 and 600 ml. 73.33% showed all Symptoms of purification. 73.33% patients showed Kaphanta vamana (Moderate expulsion of desire humor). In the level of biopurification, 66.66% patients showed moderated purification. No complication was noted with moderate drug palatability. Pharmacopeial analytical study showed its standardized values for testing the drug used for the study. It is proved as potent therapeutic emetic agent with no complication showed its clinical benefits over skin disorder like psoriasis. Seeds of Wrightia antidysenterica (WA) Linn. free from any foreign matter were selected for the study. Loss on drying revealed 6.535% moisture content

GEBR-7b, a novel PDE4D selective inhibitor that improves memory in rodents at non-emetic doses.

PubMed

Bruno, O; Fedele, E; Prickaerts, J; Parker, L A; Canepa, E; Brullo, C; Cavallero, A; Gardella, E; Balbi, A; Domenicotti, C; Bollen, E; Gijselaers, H J M; Vanmierlo, T; Erb, K; Limebeer, C L; Argellati, F; Marinari, U M; Pronzato, M A; Ricciarelli, R

2011-12-01

Strategies designed to enhance cerebral cAMP have been proposed as symptomatic treatments to counteract cognitive deficits. However, pharmacological therapies aimed at reducing PDE4, the main class of cAMP catabolizing enzymes in the brain, produce severe emetic side effects. We have recently synthesized a 3-cyclopentyloxy-4-methoxybenzaldehyde derivative, structurally related to rolipram, and endowed with selective PDE4D inhibitory activity. The aim of the present study was to investigate the effect of the new drug, namely GEBR-7b, on memory performance, nausea, hippocampal cAMP and amyloid-β (Aβ) levels. To measure memory performance, we performed object recognition tests on rats and mice treated with GEBR-7b or rolipram. The emetic potential of the drug, again compared with rolipram, was evaluated in rats using the taste reactivity test and in mice using the xylazine/ketamine anaesthesia test. Extracellular hippocampal cAMP was evaluated by intracerebral microdialysis in freely moving rats. Levels of soluble Aβ peptides were measured in hippocampal tissues and cultured N2a cells by elisa. GEBR-7b increased hippocampal cAMP, did not influence Aβ levels and improved spatial, as well as object memory performance in the object recognition tests. The effect of GEBR-7b on memory was 3 to 10 times more potent than that of rolipram, and its effective doses had no effect on surrogate measures of emesis in rodents. Our results demonstrate that GEBR-7b enhances memory functions at doses that do not cause emesis-like behaviour in rodents, thus offering a promising pharmacological perspective for the treatment of memory impairment. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Efficacy and safety of tranexamic acid as an emetic in dogs.

PubMed

Kakiuchi, Hitoshi; Kawarai-Shimamura, Asako; Fujii, Yoko; Aoki, Takuma; Yoshiike, Masaki; Arai, Hayato; Nakamura, Atsushi; Orito, Kensuke

2014-12-01

To determine dose dependency of tranexamic acid-induced emesis and the time course of the antifibrinolytic potency of tranexamic acid in dogs. 10 Beagles. In a dose-escalating experiment, ascending doses of tranexamic acid (10, 20, and 30 mg/kg, IV) were administered at 5-minute intervals until vomiting was observed. In a separate single-dose experiment, ascending doses of tranexamic acid (20, 30, 40, and 50 mg/kg, IV) were administered at 1-week intervals until vomiting was observed. Time to onset of vomiting and number of vomiting episodes were measured in both experiments. In a coagulation experiment, a single 50 mg/kg bolus of tranexamic acid was administered, and blood was obtained 1 hour before and 20 minutes, 3 hours, and 24 hours after administration. Antifibrinolytic potency of tranexamic acid was evaluated by use of a modified rotational thromboelastography method. Tranexamic acid induced vomiting in a dose-dependent manner. Vomiting frequency was ≤ 2 episodes, and vomiting concluded ≤ 250 seconds after administration. Antifibrinolytic potency of tranexamic acid was significantly higher at 20 minutes following administration, but not different by 24 hours, when compared with the potency measured before administration. No adverse effects were observed in any experiment. IV administration of tranexamic acid induced emesis in a dose-dependent manner. The antifibrinolytic potency of tranexamic acid decreased in a time-dependent manner and was resolved ≤ 24 hours after administration. Further studies are warranted to investigate the emetic and other adverse effects of tranexamic acid in dogs of various breeds and ages.

Enterotoxins and emetic toxins production by Bacillus cereus and other species of Bacillus isolated from Soumbala and Bikalga, African alkaline fermented food condiments.

PubMed

Ouoba, Labia Irene I; Thorsen, Line; Varnam, Alan H

2008-06-10

The ability of various species of Bacillus from fermented seeds of Parkia biglobosa known as African locust bean (Soumbala) and fermented seeds of Hibiscus sabdariffa (Bikalga) was investigated. The study included screening of the isolates by haemolysis on blood agar, detection of toxins in broth and during the fermentation of African locust bean using the Bacillus cereus Enterotoxin Reverse Passive Latex Agglutination test kit (BCET-RPLA) and the Bacillus Diarrhoeal Enterotoxin Visual Immunoassay (BDEVIA). Detection of genes encoding cytotoxin K (CytK), haemolysin BL (Hbl A, Hbl C, Hbl D), non-hemolytic enterotoxin (NheA, NheB, NheC) and EM1 specific of emetic toxin producers was also investigated using PCR with single pair and multiplex primers. Of 41 isolates, 29 Bacillus belonging to the species of B. cereus, Bacillus subtilis, Bacillus licheniformis and Bacillus pumilus showed haemolysis on blood agar. Using RPLA, enterotoxin production was detected for three isolates of B. cereus in broth and all B. cereus (9) in fermented seeds. Using BDEVIA, enterotoxin production was detected in broth as well as in fermented seeds for all B. cereus isolates. None of the isolates belonging to the other Bacillus species was able to produce enterotoxins either by RPLA or BDEVIA. Nhe genes were detected in all B. cereus while Hbl and CytK genes were detected respectively in five and six B. cereus strains. A weak presence of Hbl (A, D) and CytK genes was detected in two isolates of B. subtilis and one of B. licheniformis but results were inconsistent, especially for Hbl genes. The emetic specific gene fragment EM1 was not detected in any of the isolates studied.

Accelerated Blood Clearance (ABC) Phenomenon Favors the Accumulation of Tartar Emetic in Pegylated Liposomes in BALB/c Mice Liver.

PubMed

Lopes, Tamara C M; Silva, Débora F; Costa, Walyson C; Frézard, Frédéric; Barichello, José M; Silva-Barcellos, Neila M; de Lima, Wanderson G; Rezende, Simone A

2018-01-01

Tartar emetic (TE) was the first drug used to treat leishmaniasis. However, its use was discontinued due to high toxicity. Association of TE with liposomes is a strategy to reduce its side effects. Pegylated liposomes (Lpeg) present lower rates of uptake by macrophages and prolonged circulation compared to their nonpegylated counterparts. However, repeated administration of Lpeg can cause an Accelerated Blood Clearance (ABC) phenomenon, whereby recognition of liposomes by antibodies results in faster phagocytosis. This work evaluated the effect of TE administration on histopathological aspects and the effect of the ABC phenomenon on targeting and toxicity in mice. Our results show that treatment with free or liposomal TE had no effect on the erythrocyte count, on liver and spleen weight, and on hepatic, splenic, and cardiac histology in mice. Severe lesions were observed on the kidneys of animals treated with a single dose of free TE. Treatment with TE in Lpeg after induction of ABC phenomenon caused a significant increase in Sb level in the liver without toxicity. Furthermore, mice treated with TE in liposomes showed normal renal histopathology. These results suggest site-specific targeting of Sb to the liver after induction of ABC phenomenon with no toxicity to other organs.

Accelerated Blood Clearance (ABC) Phenomenon Favors the Accumulation of Tartar Emetic in Pegylated Liposomes in BALB/c Mice Liver

PubMed Central

Lopes, Tamara C. M.; Silva, Débora F.; Costa, Walyson C.; Barichello, José M.; Silva-Barcellos, Neila M.; de Lima, Wanderson G.

2018-01-01

Tartar emetic (TE) was the first drug used to treat leishmaniasis. However, its use was discontinued due to high toxicity. Association of TE with liposomes is a strategy to reduce its side effects. Pegylated liposomes (Lpeg) present lower rates of uptake by macrophages and prolonged circulation compared to their nonpegylated counterparts. However, repeated administration of Lpeg can cause an Accelerated Blood Clearance (ABC) phenomenon, whereby recognition of liposomes by antibodies results in faster phagocytosis. This work evaluated the effect of TE administration on histopathological aspects and the effect of the ABC phenomenon on targeting and toxicity in mice. Our results show that treatment with free or liposomal TE had no effect on the erythrocyte count, on liver and spleen weight, and on hepatic, splenic, and cardiac histology in mice. Severe lesions were observed on the kidneys of animals treated with a single dose of free TE. Treatment with TE in Lpeg after induction of ABC phenomenon caused a significant increase in Sb level in the liver without toxicity. Furthermore, mice treated with TE in liposomes showed normal renal histopathology. These results suggest site-specific targeting of Sb to the liver after induction of ABC phenomenon with no toxicity to other organs. PMID:29593857

Elaboration and validation of the method for the quantification of the emetic toxin of Bacillus cereus as described in EN-ISO 18465 - Microbiology of the food chain - Quantitative determination of emetic toxin (cereulide) using LC-MS/MS.

PubMed

In 't Veld, P H; van der Laak, L F J; van Zon, M; Biesta-Peters, E G

2018-04-12

A method for the quantification of the Bacillus cereus emetic toxin (cereulide) was developed and validated. The method principle is based on LC-MS as this is the most sensitive and specific method for cereulide. Therefore the study design is different from the microbiological methods validated under this mandate. As the method had to be developed a two stage validation study approach was used. The first stage (pre-study) focussed on the method applicability and the experience of the laboratories with the method. Based on the outcome of the pre-study and comments received during voting at CEN and ISO level a final method was agreed to be used for the second stage the (final) validation of the method. In the final (validation) study samples of cooked rice (both artificially contaminated with cereulide or contaminated with B. cereus for production of cereulide in the rice) and 6 other food matrices (fried rice dish, cream pastry with chocolate, hotdog sausage, mini pancakes, vanilla custard and infant formula) were used. All these samples were spiked by the participating laboratories using standard solutions of cereulide supplied by the organising laboratory. The results of the study indicate that the method is fit for purpose. Repeatability values were obtained of 0.6 μg/kg at low level spike (ca. 5 μg/kg) and 7 to 9.6 μg/kg at high level spike (ca. 75 μg/kg). Reproducibility at low spike level ranged from 0.6 to 0.9 μg/kg and from 8.7 to 14.5 μg/kg at high spike level. Recovery from the spiked samples ranged between 96.5% for mini-pancakes to 99.3% for fries rice dish. Copyright © 2018. Published by Elsevier B.V.

Class side effects: decreased pressure in the lower oesophageal and the pyloric sphincters after the administration of dopamine antagonists, neuroleptics, anti-emetics, L-NAME, pentadecapeptide BPC 157 and L-arginine.

PubMed

Belosic Halle, Zeljka; Vlainic, Josipa; Drmic, Domagoj; Strinic, Dean; Luetic, Kresimir; Sucic, Mario; Medvidovic-Grubisic, Maria; Pavelic Turudic, Tatjana; Petrovic, Igor; Seiwerth, Sven; Sikiric, Predrag

2017-05-17

The ulcerogenic potential of dopamine antagonists and L-NAME in rats provides unresolved issues of anti-emetic neuroleptic application in both patients and experimental studies. Therefore, in a 1-week study, we examined the pressures within the lower oesophageal and the pyloric sphincters in rats [assessed manometrically (cm H 2 O)] after dopamine neuroleptics/prokinetics, L-NAME, L-arginine and stable gastric pentadecapeptide BPC 157 were administered alone and/or in combination. Medication (/kg) was given once daily intraperitoneally throughout the 7 days, with the last dose at 24 h before pressure assessment. Given as individual agents to healthy rats, all dopamine antagonists (central [haloperidol (6.25 mg, 16 mg, 25 mg), fluphenazine (5 mg), levomepromazine (50 mg), chlorpromazine (10 mg), quetiapine (10 mg), olanzapine (5 mg), clozapine (100 mg), sulpiride (160 mg), metoclopramide (25 mg)) and peripheral(domperidone (10 mg)], L-NAME (5 mg) and L-arginine (100 mg) decreased the pressure within both sphincters. As a common effect, this decreased pressure was rescued, dose-dependently, by BPC 157 (10 µg, 10 ng) (also note that L-arginine and L-NAME given together antagonized each other's responses). With haloperidol, L-NAME worsened both the lower oesophageal and the pyloric sphincter pressure, while L-arginine ameliorated lower oesophageal sphincter but not pyloric sphincter pressure, and antagonized L-NAME effect. With domperidone, L-arginine originally had no effect, while L-NAME worsened pyloric sphincter pressure. This effect was opposed by L-arginine. All these effects were further reversed towards a stronger beneficial effect, close to normal pressure values, by the addition of BPC 157. In addition, NO level was determined in plasma, sphincters and brain tissue. Thiobarbituric acid reactive substances (TBARS) were also assessed. Haloperidol increased NO levels (in both sphincters, the plasma and brain), consistently producing increased

Insights into the central pathways involved in the emetic and behavioural responses to exendin-4 in the ferret.

PubMed

Lu, Zengbing; Yeung, Chi-Kong; Lin, Ge; Yew, David T W; Andrews, P L R; Rudd, John A

2017-01-01

GLP-1 receptor agonists are utilised for the treatment of Type-2 diabetes but can be associated with undesirable effects of nausea and vomiting. To investigate the role of GLP-1 receptors in mechanisms of emesis, behaviours indicative of nausea (BIN) and food intake in the ferret. Exendin-4 (10 and 30nmol, i.c.v.) induced emesis, inhibited food intake, and increased the frequency of BIN. Increases in c-Fos in the brainstem, midbrain and forebrain occurred in animals exhibiting emesis; no activation of the brainstem occurred in animals not vomiting. Exendin-4 (10nmol, i.c.v.) when preceded by i.c.v. saline (15μl), was not emetic but induced BIN and inhibited food intake; exendin (9-39) (100nmol) reduced BIN only. c-Fos showed that consistent with the absence of emesis in saline/exendin-4 treated animals there was no increase in c-Fos in the brainstem, but it increased in midbrain and forebrain nuclei. Excepting the amygdala, exendin (9-39) was without efffect on the increases in c-Fos. Analysis of c-Fos data showed a positive linear relationship between midbrain and forebrain areas irrespective of the occurrence of emesis induced by exendin-4. In contrast, brainstem and midbrain c-Fos levels were positively correlated, but only in animals with emesis. The brainstem is critical for exendin-4-induced emesis but suppression of food intake and BIN involves more rostral brain sites. Exendin-4-induced BIN and c-Fos activation of the amygdala are sensitive to exendin (9-39), whereas the suppression of food intake is not implicating separate control mechanisms for emesis and BIN. Copyright © 2016 Elsevier B.V. All rights reserved.

Rapid, High-Throughput Identification of Anthrax-Causing and Emetic Bacillus cereus Group Genome Assemblies via BTyper, a Computational Tool for Virulence-Based Classification of Bacillus cereus Group Isolates by Using Nucleotide Sequencing Data

PubMed Central

Carroll, Laura M.; Miller, Rachel A.; Wiedmann, Martin

2017-01-01

ABSTRACT The Bacillus cereus group comprises nine species, several of which are pathogenic. Differentiating between isolates that may cause disease and those that do not is a matter of public health and economic importance, but it can be particularly challenging due to the high genomic similarity within the group. To this end, we have developed BTyper, a computational tool that employs a combination of (i) virulence gene-based typing, (ii) multilocus sequence typing (MLST), (iii) panC clade typing, and (iv) rpoB allelic typing to rapidly classify B. cereus group isolates using nucleotide sequencing data. BTyper was applied to a set of 662 B. cereus group genome assemblies to (i) identify anthrax-associated genes in non-B. anthracis members of the B. cereus group, and (ii) identify assemblies from B. cereus group strains with emetic potential. With BTyper, the anthrax toxin genes cya, lef, and pagA were detected in 8 genomes classified by the NCBI as B. cereus that clustered into two distinct groups using k-medoids clustering, while either the B. anthracis poly-γ-d-glutamate capsule biosynthesis genes capABCDE or the hyaluronic acid capsule hasA gene was detected in an additional 16 assemblies classified as either B. cereus or Bacillus thuringiensis isolated from clinical, environmental, and food sources. The emetic toxin genes cesABCD were detected in 24 assemblies belonging to panC clades III and VI that had been isolated from food, clinical, and environmental settings. The command line version of BTyper is available at https://github.com/lmc297/BTyper. In addition, BMiner, a companion application for analyzing multiple BTyper output files in aggregate, can be found at https://github.com/lmc297/BMiner. IMPORTANCE Bacillus cereus is a foodborne pathogen that is estimated to cause tens of thousands of illnesses each year in the United States alone. Even with molecular methods, it can be difficult to distinguish nonpathogenic B. cereus group isolates from their

Energy modulated electron therapy using a few leaf electron collimator in combination with IMRT and 3D-CRT: Monte Carlo-based planning and dosimetric evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Yahya, Khalid; Schwartz, Matthew; Shenouda, George

2005-09-15

Energy modulated electron therapy (EMET) based on Monte Carlo dose calculation is a promising technique that enhances the treatment planning and delivery of superficially located tumors. This study investigated the application of EMET using a novel few-leaf electron collimator (FLEC) in head and neck and breast sites in comparison with three-dimensional conventional radiation therapy (3D-CRT) and intensity modulated radiation therapy (IMRT) techniques. Treatment planning was performed for two parotid cases and one breast case. Four plans were compared for each case: 3D-CRT, IMRT, 3D-CRT in conjunction with EMET (EMET-CRT), and IMRT in conjunction with EMET (EMET-IMRT), all of which weremore » performed and calculated with Monte Carlo techniques. For all patients, dose volume histograms (DVHs) were obtained for all organs of interest and the DVHs were used as a means of comparing the plans. Homogeneity and conformity of dose distributions were calculated, as well as a sparing index that compares the effect of the low isodose lines. In addition, the whole-body dose equivalent (WBDE) was estimated for each plan. Adding EMET delivered with the FLEC to 3D-CRT improves sparing of normal tissues. For the two head and neck cases, the mean dose to the contralateral parotid and brain stem was reduced relative to IMRT by 43% and 84%, and by 57% and 71%, respectively. Improved normal tissue sparing was quantified as an increase in sparing index of 47% and 30% for the head and neck and the breast cases, respectively. Adding EMET to either 3D-CRT or IMRT results in preservation of target conformity and dose homogeneity. When adding EMET to the treatment plan, the WBDE was reduced by between 6% and 19% for 3D-CRT and by between 21% and 33% for IMRT, while WBDE for EMET-CRT was reduced by up to 72% when compared with IMRT. FLEC offers a practical means of delivering modulated electron therapy. Although adding EMET delivered using the FLEC results in perturbation of target

Transdermal scopolamine: an alternative to ondansetron and droperidol for the prevention of postoperative and postdischarge emetic symptoms.

PubMed

White, Paul F; Tang, Jun; Song, Dajun; Coleman, Jayne E; Wender, Ronald H; Ogunnaike, Babatunde; Sloninsky, Alexander; Kapu, Rajani; Shah, Mary; Webb, Tom

2007-01-01

Given the controversy regarding the use of droperidol and the high cost of the 5-HT3 antagonists, a cost-effective alternative for routine use as a prophylactic antiemetic would be desirable. We designed two parallel, randomized, double-blind sham and placebo-controlled studies to compare the early and late antiemetic efficacy and adverse event profile of transdermal scopolamine (TDS) 1.5 mg, to ondansetron 4 mg IV, and droperidol 1.25 mg IV for antiemetic prophylaxis as part of a multimodal regimen in "at risk" surgical populations. A total of 150 patients undergoing major laparoscopic (n = 80) or plastic (n = 70) surgery procedures received either an active TDS patch (containing scopolamine 1.5 mg) or a similar appearing sham patch 60 min before entering the operating room. All patients received a standardized general anesthetic technique. A second study medication was administered in a 2-mL numbered syringe containing either saline (for the two active TDS groups), droperidol, 1.25 mg, or ondansetron, 4 mg (for the sham patch groups), and was administered IV near the end of the procedure. The occurrence of postoperative nausea and vomiting/retching, need for rescue antiemetics, and the complete response rates (i.e., absence of protracted nausea or repeated episodes of emesis requiring antiemetic rescue medication) was reported. In addition, complaints of visual disturbances, dry mouth, drowsiness, and restlessness were noted up to 72 h after surgery. There were no significant differences in any of the emetic outcomes or need for rescue antiemetics among the TDS, droperidol, and ondansetron groups in the first 72 h after surgery. The complete response rates varied from 41% to 51%, and did not significantly differ among the treatment groups. The overall incidence of dry mouth was significantly more frequent in the TDS groups than in the droperidol and ondansetron groups (21% vs 3%). Premedication with TDS was as effective as droperidol (1.25 mg) or ondansetron (4

The Central Nervous Connections Involved in the Vomiting Reflex

NASA Technical Reports Server (NTRS)

Brizzee, K. R.; Mehler, W. R.

1986-01-01

The vomiting reflex may be elicited by a number of different types or classes of stimuli involving many varieties of receptor structures and considerable diversity in afferent pathways and central connections. Central relay or mediating structures thus may vary widely according to the type of initial emetic stimulus. The emetic circuits which have been most completely delineated to date are probably those in which the Chemoreceptor Trigger Zone (CTZ) in the Area Postrema (AP) functions as a key mediating structure. Even in this system, however, there are large gaps in our knowledge of the nerve tracts and central nervous connections involved. Knowledge of most other emetic circuits subserving the emetic reflex resulting from many diverse types of stimuli such, for example, as emotional stress (e.g. psychogenic vomiting, Wruble et al. 1982), pain (e.g. testicular trauma), and chemical or mechanical irritation of the gastrointestinal tract or urinary tract is quite incomplete at this time, thus precluding any very adequate description of their central connections at present. One physiological system, however, which has received considerable attention recently in relation to the vomiting reflex elicited by motion stimuli is the vestibular system. Due to the paucity of data on central nervous connections of several or the non-vestibular types of emetic stimuli cited above, we will devote most of our attention in this brief review to the central connections of the vestibular system which seem likely to be involved in the vomiting response to motion stimuli. However, the latter part of the review will be concerned with the concept of the reticular vomiting centre in relation to the ParviCellular Reticular Formation (PCRF), and will thus probably pertain to all of the many classes of emetic stimuli since it will address the question of the final common emetic pathway.

Design and dosimetry of a few leaf electron collimator for energy modulated electron therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Yahya, Khalid; Verhaegen, Frank; Seuntjens, Jan

2007-12-15

Despite the capability of energy modulated electron therapy (EMET) to achieve highly conformal dose distributions in superficial targets it has not been widely implemented due to problems inherent in electron beam radiotherapy such as planning dosimetry accuracy, and verification as well as a lack of systems for automated delivery. In previous work we proposed a novel technique to deliver EMET using an automated 'few leaf electron collimator' (FLEC) that consists of four motor-driven leaves fit in a standard clinical electron beam applicator. Integrated with a Monte Carlo based optimization algorithm that utilizes patient-specific dose kernels, a treatment delivery was incorporatedmore » within the linear accelerator operation. The FLEC was envisioned to work as an accessory tool added to the clinical accelerator. In this article the design and construction of the FLEC prototype that match our compact design goals are presented. It is controlled using an in-house developed EMET controller. The structure of the software and the hardware characteristics of the EMET controller are demonstrated. Using a parallel plate ionization chamber, output measurements were obtained to validate the Monte Carlo calculations for a range of fields with different energies and sizes. Further verifications were also performed for comparing 1-D and 2-D dose distributions using energy independent radiochromic films. Comparisons between Monte Carlo calculations and measurements of complex intensity map deliveries show an overall agreement to within {+-}3%. This work confirms our design objectives of the FLEC that allow for automated delivery of EMET. Furthermore, the Monte Carlo dose calculation engine required for EMET planning was validated. The result supports the potential of the prototype FLEC for the planning and delivery of EMET.« less

Opportunities for the replacement of animals in the study of nausea and vomiting

PubMed Central

Holmes, AM; Rudd, JA; Tattersall, FD; Aziz, Q; Andrews, PLR

2009-01-01

Nausea and vomiting are among the most common symptoms encountered in medicine as either symptoms of disease or side effects of treatments. Developing novel anti-emetics and identifying emetic liability in novel chemical entities rely on models that can recreate the complexity of these multi-system reflexes. Animal models (especially the ferret and dog) are the current gold standard; however, the selection of appropriate models is still a matter of debate, especially when studying the subjective human sensation of nausea. Furthermore, these studies are associated with animal suffering. Here, following a recent workshop held to review the utility of animal models in nausea and vomiting research, we discuss the limitations of some of the current models in the context of basic research, anti-emetic development and emetic liability detection. We provide suggestions for how these limitations may be overcome using non-animal alternatives, including greater use of human volunteers, in silico and in vitro techniques and lower organisms. PMID:19371333

Pattern of prophylaxis administration for chemotherapy-induced nausea and vomiting: an analysis of city-based health insurance data.

PubMed

Nakamura, Fumiaki; Higashi, Takahiro

2013-12-01

Chemotherapy-induced nausea and vomiting (CINV) substantially affects patient quality of life. Although several guidelines have recommended the use of 5-hydroxytryptamine 3 (5HT3) receptor antagonists with glucocorticoids to alleviate acute CINV, studies in other countries have reported that these recommendations were often not followed. We aimed to assess antiemetic use in community practices just before the Japanese Guidelines for the Appropriate Use of Antiemetics were published. Using the insurance claims submitted to a public insurance program that covers residents up to 75 years old operated by a city with a population of 250,000, we examined the concurrent use of 5HT3 receptor antagonists and glucocorticoids with high or moderate emetic risk chemotherapy. Overall, 448 patients received high or moderate emetic risk chemotherapy 1,342 times during the study period. The recommended antiemetic therapy was provided in 61.9 % (95 % confidence interval 55.5-68.3 %) of the treated patients, but the moderate emetic risk chemotherapy group received the recommended antiemetic therapy less frequently than the high emetic risk chemotherapy group (55.5 vs. 82.1 %, P < 0.01). A multivariate analysis showed that the use of non-recommended antiemetics and high emetic risk chemotherapy were associated with the recommended antiemetic therapy. Breast and lung cancer patients receiving high emetic risk chemotherapy received the recommended antiemetics in 100 % of cases, while only 67 % of patients with other cancer types received the recommended antiemetics. Despite several limitations associated with analysis of insurance claims, our study indicates that substantial room for improvement exists in the practice of preventing CINV.

Does ramosetron reduce postoperative emesis and pain after TKA?

PubMed

Koh, In Jun; Chang, Chong Bum; Jeon, Young-Tae; Ryu, Jung-Hee; Kim, Tae Kyun

2012-06-01

Current pain management protocols involving many anesthetic and analgesic drugs reportedly provide adequate analgesia after TKA. However, control of emetic events associated with the drugs used in current multimodal pain management remains challenging. We determined (1) whether ramosetron prophylaxis reduces postoperative emetic events; and (2) whether it influences pain levels and opioid consumption in patients managed with a current multimodal pain management protocol after TKA. We randomized 119 patients undergoing TKA to receive either ramosetron (experimental group, n = 60) or no prophylaxis (control group, n = 59). All patients received regional anesthesia, preemptive analgesic medication, continuous femoral nerve block, periarticular injection, and fentanyl-based intravenous patient-controlled analgesia. We recorded the incidence of emetic events, rescue antiemetic requirements, complete response, pain level, and opioid consumption during three periods (0-6, 6-24, and 24-48 hours postoperatively). The severity of nausea was evaluated using a 0 to 10 VAS. The ramosetron group tended to have a lower incidence of nausea with a higher complete response and tended to have less severe nausea and fewer rescue antiemetic requirements during the 6- to 24-hour period. However, the overall incidences of emetic events, rescue antiemetic requirements, and complete response were similar in both groups. We found no differences in pain level or opioid consumption between the two groups. Ramosetron reduced postoperative emetic events only during the 6- to 24-hour postoperative period and did not affect pain relief. More efficient measures to reduce emetic events after TKA should be explored. Level I, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Impact and management of chemotherapy/radiotherapy-induced nausea and vomiting and the perceptual gap between oncologists/oncology nurses and patients: a cross-sectional multinational survey.

PubMed

Vidall, Cheryl; Fernández-Ortega, Paz; Cortinovis, Diego; Jahn, Patrick; Amlani, Bharat; Scotté, Florian

2015-11-01

Chemotherapy/radiotherapy-induced nausea and vomiting (CINV/RINV) can affect half of oncology patients, significantly impacting daily life. Nausea without vomiting has only recently been thought of as a condition in its own right. As such, the incidence of nausea is often underestimated. This survey investigated the incidence and impact of CINV/RINV in patients compared with estimations of physicians/oncology nurses to determine if there is a perceptual gap between healthcare professionals and patients. An online research survey of physicians, oncology nurses and patients was conducted across five European countries. Participants had to have experience prescribing/recommending or have received anti-emetic medication for CINV/RINV treatment. Questionnaires assessed the incidence and impact of CINV/RINV, anti-emetic usage and compliance, and attribute importance of anti-emetic medication. A total of 947 (375 physicians, 186 oncology nurses and 386 patients) participated in this survey. The incidence of nausea was greater than vomiting: 60 % of patients reported nausea alone, whereas 18 % reported vomiting. Physicians and oncology nurses overestimated the incidence of CINV/RINV but underestimated its impact on patients' daily lives. Only 38 % of patients reported full compliance with physicians'/oncology nurses' guidelines when self-administering anti-emetic medication. Leading factors for poor compliance included reluctance to add to a pill burden and fear that swallowing itself would induce nausea/vomiting. There is a perceptual gap between healthcare professionals and patients in terms of the incidence and impact of CINV/RINV. This may lead to sub-optimal prescription of anti-emetics and therefore management of CINV/RINV. Minimising the pill burden and eliminating the requirement to swallow medication could improve poor patient compliance with anti-emetic regimens.

[Personality and emesis in the patient treated with antineoplastic chemotherapy].

PubMed

Llorca, G; Martín, T; Derecho, J; Gómez, M J

1991-01-01

A sample of twenty cancer patients following chemotherapy realize MMPI questionnaire, and another one for valuation of emetic and anticipatory phenomena in relation to said therapy. The authors came to the conclusion that 36.8% of the sample had anticipatory nausea and vomiting, 63.6% anticipatory dysphoria, and 66% emetic incidents after chemotherapy. The conclusion, through comparison of personality variables, is that all patients showed neuroticism and depression scales increased, in relation to healthy population. Depression variable increased especially in patients that didn't present anticipatory nausea and vomiting. Likewise, patients with anticipatory symptoms or emetic incidents after chemotherapy present an increased social introversion variable.

Interaction between non-psychotropic cannabinoids in marihuana: effect of cannabigerol (CBG) on the anti-nausea or anti-emetic effects of cannabidiol (CBD) in rats and shrews.

PubMed

Rock, Erin M; Goodwin, Jennifer M; Limebeer, Cheryl L; Breuer, Aviva; Pertwee, Roger G; Mechoulam, Raphael; Parker, Linda A

2011-06-01

The interaction between two non-psychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG), which have been reported to act as a 5-hydroxytryptamine 1A (5-HT(1A)) agonist and antagonist, respectively, was evaluated. To evaluate the potential of CBG to reverse the anti-nausea, anti-emetic effects of CBD. In experiment 1, rats were pre-treated with CBG (0.0, 1, 5, and 10 mg/kg, ip), 15 min prior to being treated with CBD (experiment 1a: VEH or 5 mg/kg, ip) or 8-OH-DPAT (experiment 1b: VEH or 0.01 mg/kg, ip). Thirty minutes later, all rats received a pairing of 0.1% saccharin solution and LiCl (20 ml/kg of 0.15 M, ip). Seventy-two hours later, the rats received a drug-free taste reactivity test with saccharin to evaluate the effects of the treatments on the establishment of conditioned gaping reactions (a model of nausea). As well, conditioned saccharin avoidance was measured. In experiment 2, Suncus murinus were injected with CBG (5 mg/kg, ip) or VEH 15 min prior to CBD (5 mg/kg) or VEH and 30 min later were injected with LiCl (60 ml/kg of 0.15 M, i.p.), and the number of vomiting episodes were measured. CBD (5 mg/kg) suppressed conditioned gaping in rats and vomiting in shrews, which were reversed by pre-treatment with all doses of CBG. CBG also prevented the anti-nausea effects of 8-OH-DPAT. Interactions between moderate doses of CBG and CBD may oppose one another at the 5-HT(1A) receptor in the regulation of nausea and vomiting.

A phase II randomized double-blind placebo-controlled study of 6-gingerol as an anti-emetic in solid tumor patients receiving moderately to highly emetogenic chemotherapy.

PubMed

Konmun, J; Danwilai, K; Ngamphaiboon, N; Sripanidkulchai, B; Sookprasert, A; Subongkot, S

2017-04-01

6-Gingerol is a natural compound extracted from ginger. Preclinical studies demonstrated that 6-gingerol has an anti-emetic activity by inhibiting neurokinin-1, serotonin, and dopamine receptors. Several clinical trials examined crude ginger powder for preventing chemotherapy-induced nausea and vomiting (CINV), but none of them was conducted with a standardized bioactive compound. Patients who received moderately to highly emetogenic adjuvant chemotherapy were randomized to receive 6-gingerol 10 mg or placebo orally twice daily for 12 weeks. Ondansetron, metoclopramide, and dexamethasone were given to all patients. The primary endpoint was complete response (CR) rate defined as no emesis or rescue treatment at any time. Eighty-eight patients were randomized to receive 6-gingerol (N = 42) or placebo (N = 46). Most patients received highly emetogenic chemotherapy (93%). Overall CR rate was significantly higher in 6-gingerol group as compared with that of the placebo (77 vs. 32%; P < 0.001). The difference in means of appetite score was significant (P = 0.001) and more noticeable over time. Mean FACT-G score indicating quality of life was significantly higher (86.21) in 6-gingerol group at 64 days as compared with that of placebo group (72.36) (P < 0.001). No toxicity related to 6-gingerol was observed. Patients treated with 6-gingerol reported significantly less grade 3 fatigue (2 vs. 20%; P = 0.020). 6-Gingerol significantly improved overall CR rate in CINV, appetite and quality of life in cancer patients receiving adjuvant chemotherapy. A phase III randomized study of 6-gingerol is warranted to confirm these results.

Energy modulated electron therapy: Design, implementation, and evaluation of a novel method of treatment planning and delivery

NASA Astrophysics Data System (ADS)

Al-Yahya, Khalid

Energy modulated electron therapy (EMET) is a promising treatment modality that has the fundamental capabilities to enhance the treatment planning and delivery of superficially located targets. Although it offers advantages over x-ray intensity modulated radiation therapy (IMRT), EMET has not been widely implemented to the same level of accuracy, automation, and clinical routine as its x-ray counterpart. This lack of implementation is attributed to the absence of a remotely automated beam shaping system as well as the deficiency in dosimetric accuracy of clinical electron pencil beam algorithms in the presence of beam modifiers and tissue heterogeneities. In this study, we present a novel technique for treatment planning and delivery of EMET. The delivery is achieved using a prototype of an automated "few leaf electron collimator" (FLEC). It consists of four copper leaves driven by stepper motors which are synchronized with the x-ray jaws in order to form a series of collimated rectangular openings or "fieldlets". Based on Monte Carlo studies, the FLEC has been designed to serve as an accessory tool to the current accelerator equipment. The FLEC was constructed and its operation was fully automated and integrated with the accelerator through an in-house assembled control unit. The control unit is a portable computer system accompanied with customized software that delivers EMET plans after acquiring them from the optimization station. EMET plans are produced based on dose volume constraints that employ Monte Carlo pre-generated and patient-specific kernels which are utilized by an in-house developed optimization algorithm. The structure of the optimization software is demonstrated. Using Monte Carlo techniques to calculate dose allows for accurate modeling of the collimation system as well as the patient heterogeneous geometry and take into account their impact on optimization. The Monte Carlo calculations were validated by comparing them against output

Acute Radiation Sickness Amelioration Analysis

DTIC Science & Technology

1994-05-01

Emetic Drugs 16. PRICE CODE Antagonists 17. SECURITY CLASSIFICATION 18. SECURITY CLASSIFICATION 19, SECURITY CLASSIFICATION 20. LIMITATION OF ABSTRACT OF...102 UNCLASSIFIED mcuIw IA IIIcaIIin or Isis PAW CLASSFIED BY: N/A since Unclassified. DECLASSIFY ON: N/A since Unclassified. SECURITY CLASSIFICATION OF...Approximately 2000 documents relevant to the development of the candidate anti-emetic drugs ondansetron (Zofran, Glaxo Pharmaceuticals) and granisetron

Evaluation of an every-other-day palonosetron schedule to control emesis in multiple-day high-dose chemotherapy.

PubMed

Mirabile, Aurora; Celio, Luigi; Magni, Michele; Bonizzoni, Erminio; Gianni, Alessandro Massimo; Di Nicola, Massimo

2014-12-01

Efficacy of intermittent palonosetron dosing in patients undergoing multiple-day, high-dose chemotherapy (HDC) was investigated. Fifty-eight patients received palonosetron (0.25 mg intravenous [iv.]) every other day plus daily dexamethasone (8 mg iv. twice daily) dosing. The primary end point was complete control (CC; no emesis, no rescue anti-emetics, and no more than mild nausea) in the overall acute-period (until 24 h after chemotherapy completion). Acute-period CC occurred in 81% and 50% of patients receiving palonosetron and ondansetron (historical control cohort), respectively. Palonosetron (odds ratio [OR]: 4.37; p = 0.001) and a longer duration of HDC regimen (OR: 3.47; p = 0.011) independently predicted a better anti-emetic outcome. Palonosetron every other day plus daily dexamethasone is an effective anti-emetic coverage in patients undergoing HDC.

Characterization of radiation-induced emesis in the ferret

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, G.L.

1988-06-01

Forty-eight ferrets (Mustela putorius furo) were individually head-shielded and radiated with bilateral /sup 60/Co gamma radiation at 100 cGy min-1 at doses ranging between 49 and 601 cGy. The emetic threshold was observed at 69 cGy, the ED50 was calculated at 77 cGy, and 100% incidence of emesis occurred at 201 cGy. With increasing doses of radiation, the latency to first emesis after radiation decreased dramatically, whereas the duration of the prodromal period increased. Two other sets of experiments suggest that dopaminergic mechanisms play a minor role in radiation-induced emesis in the ferret. Twenty-two animals were injected either intravenously ormore » subcutaneously with 30 to 300 micrograms/kg of apomorphine. Fewer than 50% of the animals vomited to 300 micrograms/kg apomorphine; central dopaminergic receptor activation was apparent at all doses. Another eight animals received 1 mg/kg domperidone prior to either 201 (n = 4) or 401 (n = 4) cGy radiation and their emetic responses were compared with NaCl-injected-irradiated controls (n = 8). At 201 cGy, domperidone significantly reduced only the total time in emetic behavior. At 401 cGy, domperidone had no salutary effect on radiation-induced emesis. The emetic responses of the ferret to radiation and apomorphine are compared with these responses in other vomiting species.« less

Characterization of radiation-induced emesis in the ferret

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, G.L.

1988-01-01

Forty-eight ferrets (Mustela putorius furo) were individually head-shielded and radiated with bilateral cobalt 60 gamma radiation at 100 cGy min at doses ranging between 49 and 601 cGy. The emetic threshold was observed at 69 cGy, the ED 50 was calculated as 77 cGy, and 100% incidence of emesis occurred at 201 cGy. With increasing doses of radiation, the latency to first emesis after radiation decreased dramatically, whereas the duration of the prodromal period increased. Two other sets of experiments suggest that dopaminergic mechanisms play a minor role in radiation-induced emesis in the ferret. Twenty-two animals were injected either intravenouslymore » or subcutaneously with 30 to 300 micrograms /kg of apomorphine. Fewer than 50% of the animals vomited to 300 micrograms/kg apomorphine; central dopaminergic receptor activation was apparent at all doses. Another eight animals received 1 mg/kg domperidone prior to either 201 (n=4) or 401 (n=4) cGy radiation and their emetic responses were compared with NaCi-injected-irradiated controls (n=8). At 201 cGy, domperidone significantly reduced only the total time in emetic behavior. At 401 cGy, domperidone had no salutary effect on radiation-induced emesis. The emetic responses of the ferret to radiation and apomorphine are compared with these responses in other vomiting species.« less

Acute radiation sickness amelioration analysis. Technical report, 20 July 1990-19 July 1993

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robinson, S.I.; Feister, A.J.; Bareis, D.L.

1994-05-01

Three tasks were conducted under the Acute Radiation Sickness Amelioration Analysis in support of the Defense Nuclear Agency (DNA) and NATO Army Armaments Group (NAAG) Project Group 29 (PG-29) on drugs for the prevention of radiation-induced nausea and vomiting: (1) documents were collected and entered into a data base, (2) data reviews and analyses were performed, and (3) PG-29 and Triservice meetings involving anti-emetic drug development were supported and documented. Approximately 2000 documents were collected, with 1424 complete bibliographic citations entered into a WordPerfect 5.1 data base. Eight reviews and analyses addressing different aspects of the safety and efficacy ofmore » the candidate anti-emetic drugs ondansetron and granistron were prepared. Support was provided for seven international PG-29 meetings and two U.S. Triservice meetings in which the efforts of PG-29 were discussed. These tasks have enabled the DNA and PG-29 to make good progress toward the goal of recommending a serotonin type-3 (5-HT3) receptor antagonist anti-emetic drug for use in military personnel.« less

Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update

PubMed Central

Basch, Ethan; Prestrud, Ann Alexis; Hesketh, Paul J.; Kris, Mark G.; Feyer, Petra C.; Somerfield, Mark R.; Chesney, Maurice; Clark-Snow, Rebecca Anne; Flaherty, Anne Marie; Freundlich, Barbara; Morrow, Gary; Rao, Kamakshi V.; Schwartz,, Rowena N.; Lyman, Gary H.

2011-01-01

Purpose To update the American Society of Clinical Oncology (ASCO) guideline for antiemetics in oncology. Methods A systematic review of the medical literature was completed to inform this update. MEDLINE, the Cochrane Collaboration Library, and meeting materials from ASCO and the Multinational Association for Supportive Care in Cancer were all searched. Primary outcomes of interest were complete response and rates of any vomiting or nausea. Results Thirty-seven trials met prespecified inclusion and exclusion criteria for this systematic review. Two systematic reviews from the Cochrane Collaboration were identified; one surveyed the pediatric literature. The other compared the relative efficacy of the 5-hydroxytryptamine-3 (5-HT3) receptor antagonists. Recommendations Combined anthracycline and cyclophosphamide regimens were reclassified as highly emetic. Patients who receive this combination or any highly emetic agents should receive a 5-HT3 receptor antagonist, dexamethasone, and a neurokinin 1 (NK1) receptor antagonist. A large trial validated the equivalency of fosaprepitant, a single-day intravenous formulation, with aprepitant; either therapy is appropriate. Preferential use of palonosetron is recommended for moderate emetic risk regimens, combined with dexamethasone. For low-risk agents, patients can be offered dexamethasone before the first dose of chemotherapy. Patients undergoing high emetic risk radiation therapy should receive a 5-HT3 receptor antagonist before each fraction and for 24 hours after treatment and may receive a 5-day course of dexamethasone during fractions 1 to 5. The Update Committee noted the importance of continued symptom monitoring throughout therapy. Clinicians underestimate the incidence of nausea, which is not as well controlled as emesis. PMID:21947834

Compliance with National Comprehensive Cancer Network anti-emesis guidelines in a Community Hospital Cancer Center.

PubMed

Daniel, Divya; Waddell, Aubrey

2016-02-01

Nausea and vomiting are common adverse events exhibited by patients receiving chemotherapy. Prophylactic use of anti-emetic agents has been shown to reduce chemotherapy-induced nausea and vomiting. Compliance with the National Comprehensive Cancer Network anti-emesis guidelines (Version 1.2013) by practitioners in a community out-patient hospital (Blount Memorial Hospital) has been reviewed and the results are presented herein. Retrospective study of patients receiving their first cycle of chemotherapy. A total of 487 patients were reviewed from January 2005 to July 2012. In total, 70 patients were categorized in the high-risk category, 292 patients were categorized in the moderate-risk category, 60 patients were categorized in the low-risk category, and 65 patients were categorized in the minimal-risk category as per the National Comprehensive Cancer Network guidelines. Included patients were being administered the first cycle of their first treatment at Blount Memorial Hospital. Data were collected retrospectively from patient chemotherapy dispensing folders. In all, 63% of the patients received appropriate anti-emetic prophylaxis medications as per the National Comprehensive Cancer Network guidelines. Post-comparison between outcomes based on the risk category showed that patients in the moderate-risk category were most likely (91%) and patients in the low-risk category were least likely (6.67%) to receive appropriate anti-emetic prophylaxis as per the National Comprehensive Cancer Network guidelines. Overall compliance with guidelines is acceptable. Patients in the moderate risk category are most likely to receive appropriate anti-emetic prophylaxis. © The Author(s) 2014.

Effectiveness and adverse effects of the use of apomorphine and 3% hydrogen peroxide solution to induce emesis in dogs.

PubMed

Khan, Safdar A; McLean, Mary Kay; Slater, Margaret; Hansen, Steven; Zawistowski, Stephen

2012-11-01

To determine the effectiveness and adverse effects of apomorphine and 3% hydrogen peroxide solution used for emesis in dogs. Prospective observational study. 147 dogs that received apomorphine (IV or placed in the conjunctival sac) or 3% hydrogen peroxide solution (PO) to induce emesis after exposure to toxic agents. Data regarding signalment; agent information; type, dose, route, and number of emetic administrations; whether emesis was successful; number of times emesis occurred; percentage of ingested agent recovered; and adverse effects were collected via telephone during American Society for the Prevention of Cruelty to Animals Animal Poison Control Center operations and stored in a database for analysis. Mann-Whitney and Fisher exact tests were used to evaluate emetic success rates. Apomorphine and 3% hydrogen peroxide solution successfully induced emesis in 59 of 63 (94%) and 76 of 84 (90%) of dogs, respectively. Mean time to onset of emesis after the first dose of emetic was 14.5 and 18.6 minutes when hydrogen peroxide (n = 37) and apomorphine (31) were used, respectively, with mean durations of 42 and 27 minutes, respectively. Mean estimates for recovery of ingested agents were 48% for hydrogen peroxide and 52% for apomorphine. Adverse effects were reported in 16 of 112 (14%) dogs for which information was available. 3% hydrogen peroxide solution and apomorphine effectively induced emesis in dogs when used as directed. Emesis occurred within minutes after administration and helped recover substantial amounts of ingested agents. Adverse effects of both emetics were considered mild and self-limiting.

Ondansetron and promethazine have differential effects on hypothermic responses to lithium chloride administration and to provocative motion in rats

PubMed Central

Guimaraes, Drielle D; Andrews, Paul L R; Rudd, John A; Braga, Valdir A; Nalivaiko, Eugene

2015-01-01

We recently reported that provocative motion (rotation in a home cage) causes hypothermic responses in rats, similar to the hypothermic responses associated with motion sickness in humans. Many stimuli inducing emesis in species with an emetic reflex also provoke hypothermia in the rat, therefore we hypothesized that a fall in body temperature may reflect a “nausea-like” state in these animals. As rats do not possess an emetic reflex, we employed a pharmacological approach to test this hypothesis. In humans, motion- and chemically-induced nausea have differential sensitivity to anti-emetics. We thus tested whether the hypothermia induced in rats by provocative motion (rotation at 0.7 Hz) and by the emetic LiCl (63 mg/kg i.p.) have a similar differential pharmacological sensitivity. Both provocations caused a comparable robust fall in core body temperature (−1.9 ± 0.3°C and −2.0 ± 0.2°C for chemical and motion provocations, respectively). LiCl−induced hypothermia was completely prevented by ondansetron (2mg/kg, i.p., a 5-HT3 receptor antagonist that reduces cancer chemotherapy-induced nausea and vomiting), but was insensitive to promethazine (10 mg/kg, i.p., a predominantly histamine-H1 and muscarinic receptor antagonist that is commonly used to treat motion sickness). Conversely, motion-induced hypothermia was unaffected by ondansetron but promethazine reduced the rate of temperature decline from 0.20 ± 0.02 to 0.11 ± 0.03°C/min (P < 0.05) with a trend to decrease the magnitude. We conclude that this differential pharmacological sensitivity of the hypothermic responses of vestibular vs. chemical etiology in rats mirrors the observations in other pre-clinical models and humans, and thus supports the idea that a “nausea-like” state in rodents is associated with disturbances in thermoregulation. PMID:27227074

Why Can’t Rodents Vomit? A Comparative Behavioral, Anatomical, and Physiological Study

PubMed Central

Horn, Charles C.; Kimball, Bruce A.; Wang, Hong; Kaus, James; Dienel, Samuel; Nagy, Allysa; Gathright, Gordon R.; Yates, Bill J.; Andrews, Paul L. R.

2013-01-01

The vomiting (emetic) reflex is documented in numerous mammalian species, including primates and carnivores, yet laboratory rats and mice appear to lack this response. It is unclear whether these rodents do not vomit because of anatomical constraints (e.g., a relatively long abdominal esophagus) or lack of key neural circuits. Moreover, it is unknown whether laboratory rodents are representative of Rodentia with regards to this reflex. Here we conducted behavioral testing of members of all three major groups of Rodentia; mouse-related (rat, mouse, vole, beaver), Ctenohystrica (guinea pig, nutria), and squirrel-related (mountain beaver) species. Prototypical emetic agents, apomorphine (sc), veratrine (sc), and copper sulfate (ig), failed to produce either retching or vomiting in these species (although other behavioral effects, e.g., locomotion, were noted). These rodents also had anatomical constraints, which could limit the efficiency of vomiting should it be attempted, including reduced muscularity of the diaphragm and stomach geometry that is not well structured for moving contents towards the esophagus compared to species that can vomit (cat, ferret, and musk shrew). Lastly, an in situ brainstem preparation was used to make sensitive measures of mouth, esophagus, and shoulder muscular movements, and phrenic nerve activity–key features of emetic episodes. Laboratory mice and rats failed to display any of the common coordinated actions of these indices after typical emetic stimulation (resiniferatoxin and vagal afferent stimulation) compared to musk shrews. Overall the results suggest that the inability to vomit is a general property of Rodentia and that an absent brainstem neurological component is the most likely cause. The implications of these findings for the utility of rodents as models in the area of emesis research are discussed. PMID:23593236

Comparison of three preclinical models for nausea and vomiting assessment.

PubMed

Goineau, Sonia; Castagné, Vincent

Nausea is a subjective sensation often preceding emesis in humans. Drug-induced nausea remains difficult to predict in preclinical tests. The aim of this study was to compare the effects of emetic agents in rats (pica behavior), ferrets (acute and delayed phases of emesis) or dogs (emesis and cardiovascular endpoints). Rats and ferrets were administered cisplatin (±aprepitant/ondansetron or aprepitant) or apomorphine (±domperidone). Telemetered dogs were administered apomorphine (±domperidone). Food and kaolin intake was measured in rats whereas the number of emetic events was counted in ferrets and dogs. Cardiovascular changes were also monitored in dogs. In rats, cisplatin (6mg/kg, i.p.) increased kaolin intake (+2257%, p<0.001). The cisplatin effects were not reversed by the combination of aprepitant/ondansetron (2mg/kg, p.o./2mg/kg, i.p.) or by aprepitant (30mg/kg, p.o.). Apomorphine (10mg/kg, i.p.) did not induce pica behavior. In ferrets, cisplatin (8mg/kg, i.p.) induced acute and delayed emesis (371.8±47.8 emetic events over 72h) which was antagonized by aprepitant (1mg/kg, p.o.). Apomorphine (0.25mg/kg, s.c.) induced acute emesis (38.8±8.7 emetic events over 2h) which was abolished by domperidone (0.1mg/kg, s.c.). In dogs, apomorphine (100μg/kg, s.c.) induced emesis and tachycardia which were decreased by domperidone (0.2mg/kg, i.v.). The assessment of emesis in the ferret or in the dog displays a strong predictive value. In contrast, assessing nausea remains challenging in all animal species and the use of pica behavior remains questionable in the context of antiemetic drug development. Copyright © 2016 Elsevier Inc. All rights reserved.

Short pulse gastric electrical stimulation for cisplatin-induced emesis in dogs.

PubMed

Song, J; Zhong, D-X; Qian, W; Hou, X-H; Chen, J D Z

2011-05-01

In a previous study, we investigated the ameliorating effect of gastric electrical stimulation (GES) with a single set of parameters on emesis and behaviors suggestive of nausea induced by cisplatin in dogs. The aim of this study was to investigate the effects of GES with different parameters on cisplatin-induced emesis in dogs. Seven dogs implanted with gastric serosal electrodes were studied in six randomized sessions: one control session with cisplatin (2 mg kg(-1)) and five sessions with cisplatin plus GES of different parameters: GES-A: 14 Hz, 5 mA, 0.3 ms, 0.1 s on and 5 s off; GES-B: increased frequency and on-time; GES-C: increased frequency; GES-D: increased frequency and pulse width; and GES-E: increased frequency and amplitude. Gastric slow waves and emetic responses were recorded in each session. (i) Cisplatin induced emetic responses and gastric dysrhythmia. The peak time of the emetic response was during the fourth hour after cisplatin. (ii) GES with appropriate parameters reduced cisplatin-induced emesis. The number of vomiting times during the 6 h after cisplatin was 7.0 ± 1.4 in the control, 4.7 ± 1.2 with GES-A (P = 0.179), 4.2 ± 1.2 with GES-B (P = 0.109), 7.0 ± 0.8 with GES-C (P = 0.928), 2.1 ± 0.3 with GES-D (P = 0.005) and 4.7 ± 1.5 with GES-E (P = 0.129). However, none of the GES parameters could improve gastric dysrhythmia. Gastric electrical stimulation with appropriate parameters reduces cisplatin-induced emetic responses and behaviors suggestive of nausea in dogs. Among the tested parameters, GES with increased pulse width seems to produce better relief of cisplatin-induced emesis. © 2011 Blackwell Publishing Ltd.

Investigation of impact of water type on borate ore flotation.

PubMed

Ozkan, S G; Acar, A

2004-04-01

In this work, the impact of water type on borate ore flotation was investigated, while various physical parameters during flotation were considered in order to compare the results. Two different colemanite samples from Emet deposits of Turkey, named as Emet-A and Emet-B contained 44% B(2)O(3) and 40% B(2)O(3), respectively. The flotation tests were performed at feed particle size range of -210 +20 microm. Optimal consumption values for the reagents were determined as 2000 gt(-1) for AeroPromoter R825 from Cytec Company, a sulphonate type collector, 1500 gt(-1) for Procol CA927 from Allied Colloids Company, a sulphosuccinamate type collector and 100 gt(-1) for AeroFrother 70 from Cytec Company, an alcohol-type frother. In the tests, the impeller speed of the Denver-type flotation machine was set to 1200 rpm and the samples were fed into a litre cell at 25% solid/liquid ratio and at natural pH value of the slurry at room temperature. The flotation results obtained from the tests with use of tap water, demineralised water and the artificial water prepared with Ca(2+) and Mg(2+) cations deliberately added into demineralised water were compared to each other in optimal flotation conditions.

Methotrexate-induced nausea in the treatment of juvenile idiopathic arthritis.

PubMed

Falvey, Sonja; Shipman, Lauren; Ilowite, Norman; Beukelman, Timothy

2017-06-19

Methotrexate is the most commonly used disease modifying antirheumatic drug in the treatment of juvenile idiopathic arthritis and can be effective in controlling disease in many patients. A significant proportion of patients experience nausea and vomiting induced by methotrexate therapy, which can lead to decreased quality of life and discontinuation of treatment with methotrexate. Many strategies have been employed in attempts to reduce methotrexate-induced nausea, including folate supplementation, switching from oral to subcutaneous methotrexate, anti-emetic therapy, behavioral therapy, and others. Anticipatory nausea can be difficult to treat, making primary prevention of nausea with anti-emetics an attractive approach. Understanding the prevalence and impact of methotrexate-induced nausea, as well as potentially effective interventions, may help maximize the therapeutic benefits of methotrexate.

New approaches to chemotherapy-induced nausea and vomiting: from neuropharmacology to clinical investigations.

PubMed

Rubenstein, Edward B; Slusher, Barbara S; Rojas, Camilo; Navari, Rudolph M

2006-01-01

Nausea and vomiting are considered to be among the most distressing consequences of cytotoxic chemotherapies. Currently, there are several novel 5-HT(3) receptor antagonists for the treatment of chemotherapy-induced nausea and vomiting (CINV), including ondansetron, granisetron, and dolasetron. These agents provide significant improvement in the management of acute emesis but are ineffective at preventing delayed emesis. In 2003, a new 5-HT(3) receptor antagonist, palonosetron HCL (Aloxi), was introduced to the U.S. market. Palonosetron was found to be effective in preventing delayed CINV. Indeed, palonosetron was the first and only 5-HT(3) receptor antagonist approved by the FDA for the prevention of both acute and delayed CINV. More recently, studies on the role of substance P in the emetic process led to the development of aprepitant (Emend) for the prevention of delayed emesis in combination with 5-HT(3) receptor antagonists. Despite these major advances, CINV remains uncontrolled in some patients. Current efforts are focused on treating refractory emesis and include both the clinical evaluation of compounds marketed for other indications and the preclinical evaluation of novel molecules targeting other transmitters in the emetic pathway. Ongoing work in pharmacogenomics has postulated several candidate genes that could be involved in emetic sensitivity and responsiveness to antiemetic therapy. Investigations into the pharmacogenomics of CINV may someday be able to aid in the identification of high risk patients and patients unlikely to respond to conventional therapies.

Effect Size Estimates in Chemical Aversion Treatments of Alcoholism.

ERIC Educational Resources Information Center

Thurber, Steven

1985-01-01

Reports that aggregate studies on alcohol aversion therapy tended to support a moderate level of treatment impact that may have noteworthy practical import. Emetics appeared to generate fairly consistent findings; a paralysis-inducing chemical may produce variable results. (Author/NRB)

Aromatherapy for treatment of postoperative nausea and vomiting.

PubMed

Hines, Sonia; Steels, Elizabeth; Chang, Anne; Gibbons, Kristen

2012-04-18

Postoperative nausea and vomiting is a common and unpleasant phenomenon and current therapies are not always effective for all patients. Aromatherapy has been suggested as a possible addition to the available treatment strategies. This review sought to establish what effect the use of aromatherapy has on the severity and duration of established postoperative nausea and vomiting and whether aromatherapy can be used with safety and clinical effectiveness comparable to standard pharmacological treatments. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3); MEDLINE; EMBASE; CINAHL; CAM on PubMed; Meditext; LILACS; and ISI Web of Science as well as grey literature sources and the reference lists of retrieved articles. We conducted database searches up to August 2011. We included all randomized controlled trials (RCTs) and controlled clinical trials (CCTs) where aromatherapy was used to treat postoperative nausea and vomiting. Interventions were all types of aromatherapy. Aromatherapy was defined as the inhalation of the vapours of any substance for the purposes of a therapeutic benefit. Primary outcomes were the severity and duration of postoperative nausea and vomiting. Secondary outcomes were adverse reactions, use of rescue anti-emetics and patient satisfaction with treatment. Two review authors assessed risk of bias in the included studies and extracted data. As all outcomes analysed were dichotomous, we used a fixed-effect model and calculated relative risk (RR) with associated 95% confidence interval (95% CI). The nine included studies comprised six RCTs and three CCTs with a total of 402 participants. The mean age and range data for all participants were not reported for all studies. The method of randomization in four of the six included RCTs was explicitly stated and was adequate. Incomplete reporting of data affected the completeness of the analysis. Compared with placebo, isopropyl alcohol vapour

Ca2+ signaling and emesis: Recent progress and new perspectives.

PubMed

Zhong, Weixia; Picca, Andrew J; Lee, Albert S; Darmani, Nissar A

2017-01-01

Cisplatin-like chemotherapeutics cause vomiting via calcium (Ca 2+ )-dependent release of multiple neurotransmitters (dopamine, serotonin, substance P, etc.) from the gastrointestinal enterochromaffin cells and/or the brainstem. Intracellular Ca 2+ signaling is triggered by activation of diverse emetic receptors (including tachykininergic NK 1 , serotonergic 5-HT 3 , dopaminergic D 2 , cholinergic M 1 , or histaminergic H 1 ) , whose activation in vomit-competent species can evoke emesis. Other emetogens such as cisplatin, rotavirus NSP4 protein and bacterial toxins can also induce intracellular Ca 2+ elevation. Netupitant is a highly selective neurokinin NK 1 receptor (NK 1 R) antagonist and palonosetron is a selective second-generation serotonin 5-HT 3 receptor (5-HT 3 R) antagonist with a distinct pharmacological profile. An oral fixed combination of netupitant/palonosetron (NEPA; Akynzeo(®)) with >85% antiemetic efficacy is available for use in the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). Cannabinoid CB 1 receptor agonists possess broad-spectrum antiemetic activity since they prevent vomiting caused by a variety of emetic stimuli including the chemotherapeutic agent cisplatin, 5-HT 3 R agonists, and D 2 R agonists. Our findings demonstrate that application of the L-type Ca 2+ channel (LTCC) agonist FPL 64176 and the intracellular Ca 2+ mobilizing agent thapsigargin (a sarco/endoplasmic reticulum Ca 2+ -ATPase inhibitor) cause vomiting in the least shrew. On the other hand, blockade of LTCCs by corresponding antagonists (nifedipine or amlodipine) not only provide broad-spectrum antiemetic efficacy against diverse agents that specifically activate emetogenic receptors such as 5-HT 3 , NK 1 , D 2 , and M 1 receptors, but can also potentiate the antiemetic efficacy of palonosetron against the non-specific emetogen, cisplatin. In this review, we will provide an overview of Ca 2+ involvement in the emetic process; discuss the

Estimation of body surface area in the musk shrew ( Suncus murinus): a small animal for testing chemotherapy-induced emesis.

PubMed

Eiseman, Julie L; Sciullo, Michael; Wang, Hong; Beumer, Jan H; Horn, Charles C

2017-10-01

Several cancer chemotherapies cause nausea and vomiting, which can be dose-limiting. Musk shrews are used as preclinical models for chemotherapy-induced emesis and for antiemetic effectiveness. Unlike rats and mice, shrews possess a vomiting reflex and demonstrate an emetic profile similar to humans, including acute and delayed phases. As with most animals, dosing of shrews is based on body weight, while translation of such doses to clinically equivalent exposure requires doses based on body surface area. In the current study body surface area in musk shrews was directly assessed to determine the Meeh constant (K m ) conversion factor (female = 9.97, male = 9.10), allowing estimation of body surface area based on body weight. These parameters can be used to determine dosing strategies for shrew studies that model human drug exposures, particularly for investigating the emetic liability of cancer chemotherapeutic agents.

Emergency department management of gastro-enteritis in Australia and New Zealand.

PubMed

Schutz, Jacquie; Babl, Franz E; Sheriff, Nisa; Borland, Meredith

2008-10-01

Comparison of clinical practice guideline (CPG) recommendations and reported physician management of gastro-enteritis at Paediatric Research in Emergency Departments International Collaborative (PREDICT) network sites as a baseline for further randomised controlled trials. Two part survey comprising: (i) review of CPGs from PREDICT sites for gastro-enteritis; and (ii) survey of senior emergency department physicians regarding the management of gastro-enteritis. All 11 PREDICT sites participated. Nine CPGs were available with three sites using a common CPG. For moderate dehydration, eight CPGs advocated nasogastric (NG) rehydration in preference to intravenous (IV) rehydration. The IV route was reserved for severe dehydration or failed NG rehydration. In the second component of the survey, 78 of 83 (94%) physicians responded. In moderate dehydration, 82% of respondents used NG rehydration. In severe dehydration, 86% used IV fluids; 12% used NG and 3% an initial IV bolus followed by NG fluid. Serum electrolytes were measured universally with IV fluid use and by 22% using NG rehydration. The IV fluid bolus was with normal saline (86%). Fifty-four per cent used anti-emetics 'rarely' or 'sometimes'. The commonest agents were ondansetron (60%) and metoclopramide (29%). CPG recommendations and physician practice for the management of gastro-enteritis were similar across PREDICT sites with a focus on NG for moderate dehydration and IV for severe dehydration. A variety of fluids and administration rates were used. Anti-emetics were used infrequently. The efficacy and safety of newer anti-emetics should be explored in collaborative studies. Collaborative development of new CPGs should be considered to simplify fluid regimens.

Evaluation of putative neurochemical intermediaries in space/motion sickness

NASA Technical Reports Server (NTRS)

Lucot, James B.; Crampton, George H.

1991-01-01

The topics covered include the following: the emetic stimuli used on the cats in the study; analysis of the constituents of the cerebral spinal fluid (CSF) during motion sickness; evaluation of serotonin-1A agonists; other 5-HT receptors; and additional studies and activities.

A probability model for enterotoxin production of Bacillus cereus as a function of pH and temperature

USDA-ARS?s Scientific Manuscript database

Bacillus cereus is frequently isolated from a variety of foods including vegetables, dairy products, meat, and other raw and processed foods. The bacterium is capable of producing enterotoxin and emetic toxin that can cause severe nausea, vomiting and diarrhea. The objectives of this study were to a...

Alcohol-Aversion Therapy: Relation Between Strength of Aversion and Abstinence.

ERIC Educational Resources Information Center

Cannon, Dale S.; And Others

1986-01-01

Assessed degree of alcohol aversion in 60 alcoholics who received emetic alcohol-aversion therapy. Results revealed changes in response to alcoholic, but not to nonalcoholic, flavors, including decreased consumption in taste tests, more negative flavor ratings, overt behavioral indicants of aversion and increased tachycardiac response. (Author/NB)

Management of corneal decompensation 4 decades after Sputnik intraocular lens implantation.

PubMed

Hirji, Nashila; Nanavaty, Mayank A

2015-01-01

We report an unusual case of corneal decompensation occurring four decades after complicated cataract extraction with implantation of a Sputnik intraocular lens (IOL) and highlight the clinical and practical issues faced in managing corneal decompensation with a Sputnik IOL. A 72-year-old woman presented with deterioration of the vision in her left eye, four decades after intracapsular cataract extraction with Sputnik IOL implantation. Ocular examination revealed diffuse corneal edema and thickened vitreous strands in the anterior chamber. Her best-corrected visual acuity (BCVA) worsened to 6/60 within 3 months. Anterior vitrectomy and inferior iridectomy combined with Desçemet-stripping automated endothelial keratoplasty was performed. The procedure was successful, with the patient achieving best-corrected visual acuity of 6/6 at 8 months postoperatively. Corneal decompensation after Sputnik IOL implantation can occur four decades later. When the historical preoperative visual acuity is good in such cases, careful anterior vitrectomy with Desçemet-stripping automated endothelial keratoplasty provides good visual rehabilitation.

Peptide-induced emesis in dogs: possible relevance to radiation-induced emesis. Final report Oct 80-Sep 81

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carpenter, D.O.

1982-09-01

Results of earlier investigators indicate that radioemesis is mediated by some humoral agent(s). Peptides are likely candiates since they exert a number of biological effects and are released from storage sites by various stimuli, including radiation. Peptides at various concentrations were injected singly intravenously into conscious dogs, and the dog's emetic response was observed. Of the peptides tested, neurotensin, angiotensin II, vasopressin, oxytocin, and TRH produced consistent emetic responses. Inhibition of drug-induced emesis was studied both centrally (chlorpromazine) and peripherally (domperidone) acting dopamine antagonists. Results indicate inhibition by chlorpromazine, which crosses the blood brain barrier, but only partial blockade bymore » domperidone, which does not cross the blood brain barrier. Preliminary studies were conducted attempting to characterize types of receptors on area postrema neurons. Single-cell recordings from these neurons, challenged by iontophoretic administration of various neurotransmitters, show stimulation by glutamic acid and serotonin and inhibiiton by norepinephrine.« less

Hollow silicon microneedle array based trans-epidermal antiemetic patch for efficient management of chemotherapy induced nausea and vomiting

NASA Astrophysics Data System (ADS)

Kharbikar, Bhushan N.; Kumar S., Harish; Kr., Sindhu; Srivastava, Rohit

2015-12-01

Chemotherapy Induced Nausea and Vomiting (CINV) is a serious health concern in the treatment of cancer patients. Conventional routes for administering anti-emetics (i.e. oral and parenteral) have several drawbacks such as painful injections, poor patient compliance, dependence on skilled personnel, non-affordability to majority of population (parenteral), lack of programmability and suboptimal bioavailability (oral). Hence, we have developed a trans-epidermal antiemetic drug delivery patch using out-of-plane hollow silicon microneedle array. Microneedles are pointed micron-scale structures that pierce the epidermal layer of skin to reach dermal blood vessels and can directly release the drug in their vicinity. They are painless by virtue of avoiding significant contact with dermal sensory nerve endings. This alternate approach gives same pharmacodynamic effects as par- enteral route at a sparse drug-dose requirement, hence negligible side-effects and improved patient compliance. Microneedle design attributes were derived by systematic study of human skin anatomy, natural micron-size structures like wasp-sting and cactus-spine and multi-physics simulations. We used deep reactive ion etching with Bosch process and optimized recipe of gases to fabricate high-aspect-ratio hollow silicon microneedle array. Finally, microneedle array and polydimethylsiloxane drug reservoir were assembled to make finished anti-emetic patch. We assessed microneedles mechanical stability, physico-chemical properties and performed in-vitro, ex- vivo and in-vivo studies. These studies established functional efficacy of the device in trans-epidermal delivery of anti-emetics, its programmability, ease of use and biosafety. Thus, out-of-plane hollow silicon microneedle array trans-epidermal antiemetic patch is a promising strategy for painless and effective management of CINV at low cost in mainstream healthcare.

Evaluation of the antiemetic efficacy of maropitant in dogs medicated with morphine and acepromazine.

PubMed

Lorenzutti, A Matías; Martín-Flores, Manuel; Litterio, Nicolás J; Himelfarb, Martín A; Zarazaga, M Pilar

2016-03-01

To evaluate whether maropitant (1 mg kg(-1)) injected subcutaneously (SC), administered simultaneously or 30 minutes prior to intramuscular (IM) administration of morphine (0.5 mg kg(-1)) and acepromazine (0.05 mg kg(-1)), reduces the incidence of salivation, retching and emesis in dogs. Randomized, controlled, prospective clinical trial. Sixty dogs scheduled for an ovariohysterectomy as part of a population control program. Dogs were randomly allocated to be administered maropitant (1 mg kg(-1)) SC simultaneously (group M0) or 30 minutes prior to (group M30) administration of morphine (0.5 mg kg(-1)) and acepromazine (0.05 mg kg(-1)) IM. A control group was administered normal saline (C) at T-30 and T0. Dogs were observed for 30 minutes after morphine-acepromazine administration. The occurrence of vomiting, retching and salivation were recorded, as well as the time to first emesis and the number of emetic events per dog. The occurrence of salivation was not different between the groups. Retching and vomiting occurred significantly less frequently in M30 than in the other two groups (p < 0.02). The number of emetic events was also significantly less for M30 than for the other two groups (p = 0.01). When emesis occurred, the time to the first emetic event was similar among the groups. Maropitant (1 mg kg(-1)) SC reduced the frequency of morphine-induced emesis by as much as 70% when administered 30 minutes in advance. Simultaneous administration of maropitant and morphine-acepromazine produced no measurable effect on the frequency of retching or vomiting. © 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT1A somatodendritic autoreceptors in the dorsal raphe nucleus

PubMed Central

Rock, EM; Bolognini, D; Limebeer, CL; Cascio, MG; Anavi-Goffer, S; Fletcher, PJ; Mechoulam, R; Pertwee, RG; Parker, LA

2012-01-01

BACKGROUND AND PURPOSE To evaluate the hypothesis that activation of somatodendritic 5-HT1A autoreceptors in the dorsal raphe nucleus (DRN) produces the anti-emetic/anti-nausea effects of cannabidiol (CBD), a primary non-psychoactive cannabinoid found in cannabis. EXPERIMENTAL APPROACH The potential of systemic and intra-DRN administration of 5-HT1A receptor antagonists, WAY100135 or WAY100635, to prevent the anti-emetic effect of CBD in shrews (Suncus murinus) and the anti-nausea-like effects of CBD (conditioned gaping) in rats were evaluated. Also, the ability of intra-DRN administration of CBD to produce anti-nausea-like effects (and reversal by systemic WAY100635) was assessed. In vitro studies evaluated the potential of CBD to directly target 5-HT1A receptors and to modify the ability of the 5-HT1A agonist, 8-OH-DPAT, to stimulate [35S]GTPγS binding in rat brainstem membranes. KEY RESULTS CBD suppressed nicotine-, lithium chloride (LiCl)- and cisplatin (20 mg·kg−1, but not 40 mg·kg−1)-induced vomiting in the S. murinus and LiCl-induced conditioned gaping in rats. Anti-emetic and anti-nausea-like effects of CBD were suppressed by WAY100135 and the latter by WAY100635. When administered to the DRN: (i) WAY100635 reversed anti-nausea-like effects of systemic CBD, and (ii) CBD suppressed nausea-like effects, an effect that was reversed by systemic WAY100635. CBD also displayed significant potency (in a bell-shaped dose–response curve) at enhancing the ability of 8-OH-DPAT to stimulate [35S]GTPγS binding to rat brainstem membranes in vitro. Systemically administered CBD and 8-OH-DPAT synergistically suppressed LiCl-induced conditioned gaping. CONCLUSIONS AND IMPLICATIONS These results suggest that CBD produced its anti-emetic/anti-nausea effects by indirect activation of the somatodendritic 5-HT1A autoreceptors in the DRN. LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this

Animal-Model Studies of Radiation-Induced Emesis and Its Control.

DTIC Science & Technology

1982-08-01

result of 6-OHDA was similar to that of haloperidol , one action of which is catecholamine receptor neuron blocking. The fact that 6- OHDA works strictly at...minutes preexposure n = 12 Delayed onset times Haloperidol Catecholamine Reduced number of S.2w, mg/kg i.m. blocker emetic episodes 45 :iinutes

Plant compounds enhance assay sensitivity for detection of active bacillus cereus toxin

USDA-ARS?s Scientific Manuscript database

Bacillus cereus is an important food pathogen, producing emetic and diarrheal syndromes, the latter mediated by enterotoxins. It has been estimated that there are 84,000 cases of B. cereus food poisoning in the US each year, with an annual cost of USD 36 million. The ability to sensitively trace and...

What is Microsoft EMET and Why Should I Care?

DTIC Science & Technology

2014-10-22

Headquarters Services , Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington VA 22202-4302. Respondents should...William 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Software Engineering Institute...with Carnegie Mellon University for the operation of the Software Engineering Institute, a federally funded research and development center sponsored by

Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting.

PubMed

Duran, Marta; Pérez, Eulàlia; Abanades, Sergio; Vidal, Xavier; Saura, Cristina; Majem, Margarita; Arriola, Edurne; Rabanal, Manel; Pastor, Antoni; Farré, Magí; Rams, Neus; Laporte, Joan-Ramon; Capellà, Dolors

2010-11-01

Despite progress in anti-emetic treatment, many patients still suffer from chemotherapy-induced nausea and vomiting (CINV). This is a pilot, randomized, double-blind, placebo-controlled phase II clinical trial designed to evaluate the tolerability, preliminary efficacy, and pharmacokinetics of an acute dose titration of a whole-plant cannabis-based medicine (CBM) containing delta-9-tetrahydrocannabinol and cannabidiol, taken in conjunction with standard therapies in the control of CINV. Patients suffering from CINV despite prophylaxis with standard anti-emetic treatment were randomized to CBM or placebo, during the 120 h post-chemotherapy period, added to standard anti-emetic treatment. Tolerability was measured as the number of withdrawals from the study during the titration period because of adverse events (AEs). The endpoint for the preliminary efficacy analysis was the proportion of patients showing complete or partial response. Seven patients were randomized to CBM and nine to placebo. Only one patient in the CBM arm was withdrawn due to AEs. A higher proportion of patients in the CBM group experienced a complete response during the overall observation period [5/7 (71.4%) with CMB vs. 2/9 (22.2%) with placebo, the difference being 49.2% (95% CI 1%, 75%)], due to the delayed period. The incidence of AEs was higher in the CBM group (86% vs. 67%). No serious AEs were reported. The mean daily dose was 4.8 sprays in both groups. Compared with placebo, CBM added to standard antiemetic therapy was well tolerated and provided better protection against delayed CINV. These results should be confirmed in a phase III clinical trial. © 2010 Department of Health, Generalitat of Catalonia. British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.

Effect of Ablation of Area Postrema on Frequency and Latency of Motion Sickness-Induced Emesis in the Squirrel Monkey

NASA Technical Reports Server (NTRS)

Brizzee, K. R.; Ordy, J. M.; Mehler, W. R.

1980-01-01

Twelve young adult squirrel monkeys of the Bolivian subspecies were subjected to continuous counter-clockwise horizontal rotary motion at 25 rpm, together with a sinusoidal vertical excursion of 6 in. every 2 sec (0.5 Hz). Each animal was exposed to this motion regimen for a period of 60 min once each week for three consecutive weeks. Following the third weekly motion test bilateral ablation of the Area Postrema (AP) was performed in eight of the animals by thermal cautery. Two control animals were sham-operated after the third motion test while two additional controls were given the motion tests as noted above but were not operated. The four controls were considered as a single group for statistical analyses of results of the motion tests. After a recovery period of 30 to 40 days, and at a comparable interval in the non-operated controls, each animal was again tested for motion sensitivity for three consecutive weeks. The brains of all of the animals were then fixed by left ventriculal cardiac perfusion with Bouin's fluid and processed for histological evaluation of the bilateral AP ablation in comparison with the control brains. Five of the AP-ablated animals postoperatively were completely refractory to the motion stimuli, two exhibited a decreased number of emetic responses, and one exhibited the same number of responses before and after the AP lesions. The controls exhibited no significant difference in emetic sensitivity on the second series of three weekly tests than on the first series. The results of this investigation appear to be in agreement with the observations of Wang and Chinn in the dog indicating that the integrity of the AP (CTZ) is essential to the emetic response to motion.

21 CFR 201.308 - Ipecac syrup; warnings and directions for use for over-the-counter sale.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Ipecac syrup; warnings and directions for use for over-the-counter sale. 201.308 Section 201.308 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... poisonings, ipecac syrup is considered the emetic of choice. The immediate availability of this drug for use...

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tuor, U.I.; Kondysar, M.H.; Harding, R.K.

1988-06-01

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

Structural basis of ligand recognition in 5-HT3 receptors

PubMed Central

Kesters, Divya; Thompson, Andrew J; Brams, Marijke; van Elk, René; Spurny, Radovan; Geitmann, Matthis; Villalgordo, Jose M; Guskov, Albert; Helena Danielson, U; Lummis, Sarah C R; Smit, August B; Ulens, Chris

2013-01-01

The 5-HT3 receptor is a pentameric serotonin-gated ion channel, which mediates rapid excitatory neurotransmission and is the target of a therapeutically important class of anti-emetic drugs, such as granisetron. We report crystal structures of a binding protein engineered to recognize the agonist serotonin and the antagonist granisetron with affinities comparable to the 5-HT3 receptor. In the serotonin-bound structure, we observe hydrophilic interactions with loop E-binding site residues, which might enable transitions to channel opening. In the granisetron-bound structure, we observe a critical cation–π interaction between the indazole moiety of the ligand and a cationic centre in loop D, which is uniquely present in the 5-HT3 receptor. We use a series of chemically tuned granisetron analogues to demonstrate the energetic contribution of this electrostatic interaction to high-affinity ligand binding in the human 5-HT3 receptor. Our study offers the first structural perspective on recognition of serotonin and antagonism by anti-emetics in the 5-HT3 receptor. PMID:23196367

Antiemetic therapy for non-anthracycline and cyclophosphamide moderately emetogenic chemotherapy.

PubMed

Inui, Naoki

2017-05-01

Although antiemetic management in cancer therapy has improved, chemotherapy-induced nausea and vomiting remain common and troubling adverse events. Chemotherapeutic agents are classified based on their emetogenic effects, and appropriate antiemetics are recommended according to this categorization. Chemotherapy categorized as moderately emetogenic is associated with a wide spectrum of emetic risks. Combined anthracycline and cyclophosphamide regimens have been recently reclassified as highly emetogenic chemotherapy regimen. This review focuses on antiemetic pharmacotherapy in patients receiving non-anthracycline and cyclophosphamide-based moderately emetogenic chemotherapy regimens. Combination therapy with a 5-hydroxytryptamine-3 receptor agonist, preferably palonosetron, and dexamethasone is the standard therapy in moderately emetogenic chemotherapy, although triple therapy with add-on neurokinin-1 receptor antagonist is used as an alternative treatment strategy. Among moderately emetogenic chemotherapy regimens, carboplatin-containing chemotherapy has considerable emetic potential, particularly during the delayed phase. However, the additional of a neurokinin-1 receptor antagonist to the standard antiemetic therapy prevents carboplatin-induced nausea and vomiting. For regimens including oxaliplatin, the benefit of adding neurokinin-1 receptor antagonist requires further clarification.

Delta-9-tetrahydrocannabinol and cannabidiol, but not ondansetron, interfere with conditioned retching reactions elicited by a lithium-paired context in Suncus murinus: An animal model of anticipatory nausea and vomiting.

PubMed

Parker, Linda A; Kwiatkowska, Magdalena; Mechoulam, Raphael

2006-01-30

Chemotherapy patients report not only acute nausea and vomiting during the treatment itself, but also report anticipatory nausea and vomiting upon re-exposure to the cues associated with the treatment. We present a model of anticipatory nausea based on the emetic reactions of the Suncus murinus (musk shrew). Following three pairings of a novel distinctive contextual cue with the emetic effects of an injection of lithium chloride, the context acquired the potential to elicit conditioned retching in the absence of the toxin. The expression of this conditioned retching reaction was completely suppressed by pretreatment with each of the principal cannabinoids found in marijuana, Delta(9)-tetrahydrocannabinol or cannabidiol, at a dose that did not suppress general activity. On the other hand, pretreatment with a dose of ondansetron (a 5-HT(3) antagonist) that interferes with acute vomiting in this species, did not suppress the expression of conditioned retching during re-exposure to the lithium-paired context. These results support anecdotal claims that marijuana, but not ondansetron, may suppress the expression of anticipatory nausea.

Analysis of droppings to describe diets of small birds

Treesearch

Carol Pearson Ralph; Stephanie E. Nagata; C. John Ralph

1985-01-01

Stomach contents have been the major source of dietary information for small birds and other vertebrates. However, killing specimens to look at stomach contents is not an option in studies of endangered species and often is undesirable in other studies. Emetics, causing regurgitation of stomach contents, can be used successfully with small birds, but can stress and...

Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy.

PubMed

Smith, Lesley A; Azariah, Fredric; Lavender, Verna T C; Stoner, Nicola S; Bettiol, Silvana

2015-11-12

Cannabis has a long history of medicinal use. Cannabis-based medications (cannabinoids) are based on its active element, delta-9-tetrahydrocannabinol (THC), and have been approved for medical purposes. Cannabinoids may be a useful therapeutic option for people with chemotherapy-induced nausea and vomiting that respond poorly to commonly used anti-emetic agents (anti-sickness drugs). However, unpleasant adverse effects may limit their widespread use. To evaluate the effectiveness and tolerability of cannabis-based medications for chemotherapy-induced nausea and vomiting in adults with cancer. We identified studies by searching the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and LILACS from inception to January 2015. We also searched reference lists of reviews and included studies. We did not restrict the search by language of publication. We included randomised controlled trials (RCTs) that compared a cannabis-based medication with either placebo or with a conventional anti-emetic in adults receiving chemotherapy. At least two review authors independently conducted eligibility and risk of bias assessment, and extracted data. We grouped studies based on control groups for meta-analyses conducted using random effects. We expressed efficacy and tolerability outcomes as risk ratio (RR) with 95% confidence intervals (CI). We included 23 RCTs. Most were of cross-over design, on adults undergoing a variety of chemotherapeutic regimens ranging from moderate to high emetic potential for a variety of cancers. The majority of the studies were at risk of bias due to either lack of allocation concealment or attrition. Trials were conducted between 1975 and 1991. No trials involved comparison with newer anti-emetic drugs such as ondansetron. Comparison with placebo People had more chance of reporting complete absence of vomiting (3 trials; 168 participants; RR 5.7; 95% CI 2.6 to 12.6; low quality evidence

Advanced Cancer Detection Center

DTIC Science & Technology

2009-01-01

Hydrochloride (Periactin®), With and Without a Nutritional Supplement, PediaSure, on Weight in Children with Cancer/Treatment Related Cachexia (HLMCC 0702...Prevention of Cancer/Treatment-Related Cachexia in Children Receiving Moderate to Highly Emetic Chemotherapy (HLMCC 0703) • Modafinil to Improve...hydrochloride (periactin) and megestrol acetate (megace) on weight in children with cancer/treatment-related cachexia . J Pediatr Hematol Oncol. 30(11

Metabolism of clebopride in vitro. Mass spectrometry and identification of products of amide hydrolysis and N-debenzylation.

PubMed

Huizing, G; Beckett, A H; Segura, J; Bakke, O M

1980-03-01

1. Electron impact and field desorption mass spectrometry is described and discussed for clebopride, a newly developed benzamide with anti-emetic and anti-dopaminergic properties, and for some related compounds. 2. When clebopride was incubated with liver homogenates of rabbits, 4-amino-5-chloro-2-methoxybenzoic acid and N-(4'-piperidyl)-4-amino-5-chloro-2-methoxybenzamide were identified as metabolites.

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

PubMed

Osborne, R; Grove, A; Oh, P; Mabry, T J; Ng, J C; Seawright, A A

1994-07-08

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

Responses of Siberian ferrets to secondary zinc phosphide poisoning

USGS Publications Warehouse

Hill, E.F.; Carpenter, J.W.

1982-01-01

The hazard of operational-type applications of zinc phosphide (Zn3P2) on a species closely related to the black-footed ferret (Mustela nigripes), was evaluated by feeding 16 Siberian ferrets (M. eversmanni) rats that had been killed by consumption of 2% zinc phosphide treated bait or by an oral dose of 40, 80, or 160 mg of Zn3P2. All ferrets accepted rats and a single emesis by each of 3 ferrets was the only evidence of acute intoxication. All ferrets learned to avoid eating gastrointestinal tracts of the rats. Subacute zinc phosphide toxicity in the ferrets was indicated by significant decreases (18-48%) in hemoglobin, increases of 35-91 % in serum iron, and elevated levels of serum globulin, cholesterol, and triglycerides. Hemoglobin/iron, urea nitrogen/creatinine, and albumin/globulin ratios also were altered by the treatments. This study demonstrated that Siberian ferrets, or other species with a sensitive emetic reflex, are afforded a degree of protection from acute zinc phosphide poisoning due to its emetic action. The importance of toxicity associated with possible respiratory, liver, and kidney damage indicated by altered blood chemistries is not known.

Efficacy of tropisetron in patients with advanced non-small-cell lung cancer receiving adjuvant chemotherapy with carboplatin and taxanes.

PubMed

Tsavaris, N; Kosmas, C; Kopterides, P; Vadiaka, M; Kosmas, N; Skopelitis, H; Karadima, D; Kolliokosta, G; Tzima, E; Loukeris, D; Pagouni, E; Batziou, E; Xyla, V; Koufos, C

2008-03-01

Even though significant progress has been made, chemotherapy-induced emesis remains a challenging problem. Few studies focus on emesis in patients treated with carboplatin and the observation period is limited to the initial 24 h following chemotherapy. Thus, we investigated if tropisetron (T) monotherapy can adequately prevent acute and delayed emesis in non-small-cell lung cancer (NSCLC) patients receiving a moderately emetogenic chemotherapy (MEC) (carboplatin-containing) regimen. Furthermore, we explored the merits of adding dexamethasone (D) or alprazolam (A) to T, especially in the setting of a pre-existing high level of stress. We studied 60 patients with advanced NSCLC receiving carboplatin and taxanes in three consecutive cycles. During the first cycle, patients received 5 mg of T intravenously before chemotherapy and the same dose per os on each of the following 3 days. In the second cycle, T was co-administered with 8 mg of D once a day, while, during the third cycle, T was combined with per os A 0.25 mg every 12 h and continued over the following 3 days. Finally, we evaluated the impact of stress on the anti-emetic response achieved with the previously described regimens. The combination of T + A was superior to T monotherapy and the combination of T + D, regarding the prevention of acute and delayed emesis. Both T + A and T + D combinations led to appetite improvement, while patients receiving T + A experienced sedation more frequently. Interestingly, subgroup analysis revealed that patients without underlying stress obtained no further benefit by the addition of A or D, while both T + A and T + D combinations led to a better anti-emetic response in patients with stress. In conclusion, T monotherapy provides a satisfactory result in controlling nausea and emesis caused by a MEC regimen in patients without stress. However, the addition of D and, mainly, A improves its anti-emetic effect in patients with obvious stress.

Emesis and Defecations Induced by the 5-Hydroxytryptamine (5-HT3) Receptor Anatagonist Zacopride in the Ferret

DTIC Science & Technology

1990-02-16

TERMS 8. NUMBER OF PAGES 8 16. PRICE CODE 17 SECURITY CLASSIFICATION is. SECURITY CLASSIFICATION 19. SECURITY CLASSIFICATION 20. LIMITATION OF OP...the Defense Nuclear erties, i.e., granisetron [BRL43694; Endo-N-[9-methyl-9-aza- Agency has been given or should be inferred. Research was conducted...BMY25801, batanopride; BRL43694, granisetron ; GI, gastrointestinal; ACh, acetylcholine. 1034 1990 Emetic Properties of Zacopnde 1035 benzamide HCI; Gylys et

Spatial Orientation in Flight

DTIC Science & Technology

1993-11-01

activating system or the vestibular efferent system , or both, are responsible for the resulting heightened arousal and enhanced vestibular information...the emetic response to poisons. When an animal ingests a tý.xc substance and experiences its effects on the central nervous system ---,m,-!y...ACCELERATION ax,xy,az ANGULAR REACTION RxRy,Rz Figure 2. System for describing acceleratiots and inertial reactions in humans . (Adapted from Hixson et

Detection of toxigenic Bacillus cereus strains isolated from vegetables in Mexico City.

PubMed

Flores-Urbán, Karen A; Natividad-Bonifacio, Iván; Vázquez-Quiñones, Carlos R; Vázquez-Salinas, Carlos; Quiñones-Ramírez, Elsa Irma

2014-12-01

Bacillus cereus can cause diarrhea and emetic syndromes after ingestion of food contaminated with it. This ability is due to the production of enterotoxins by this microorganism, these being the hemolysin BL complex, which is involved in the diarrheal syndrome, and cereulide, which is responsible for the emetic syndrome. The detection of genes associated with the production of these toxins can predict the virulence of strains isolated from contaminated food. In this paper, we analyzed 100 samples of vegetables, 25 of each kind (broccoli, coriander, carrot, and lettuce) obtained from different markets in Mexico City and its metropolitan area. B. cereus was isolated in 32, 44, 84, and 68% of the samples of broccoli, carrot, lettuce, and coriander, respectively. The hblA gene (encoding one of the three subunits of hemolysin BL) was amplified in 100% of the B. cereus isolates, and the ces gene (encoding the cereulide) could not be amplified from any of them. This is the first report of B. cereus isolation from the vegetables analyzed in this work and, also, the first report in Mexico of the isolation from vegetables of strains with potential virulence. The results should serve as evidence of the potential risk of consuming these foods without proper treatment.

Area postrema ablations in cats: Evidence for separate neural routes for motion- and xylazine-induced CTA and emesis

NASA Technical Reports Server (NTRS)

Corcoran, Meryl Lee; Fox, Robert A.; Brizzee, Kenneth R.; Crampton, G.; Daunton, Nancy G.

1991-01-01

Previous studies on the role of the area postrema (AP) in vomiting induced in the cat by motion and drugs have shown that the AP is not essential for motion-induced vomiting, but is necessary for vomiting to apomorphine and xylazine. To confirm these findings and to determine the role of the AP in the formation of Conditioned Taste Aversion (CTA), the AP was ablated bilaterally in 10 adult female cats. With one exception, the ablated cats continued to vomit to the same motion that elicited emesis before the ablation. Doses of xylazine and apomorphine that elicit emesis in intact cats, failed to induce emesis in the ablated cats. Histological examination indicated that 8 cats had complete lesions and 2 had partial lesions. Investigations of effects of AP ablations on CTA revealed that cats with complete lesions did not form CTA to flavored milk paired with xylazine-induced CTA. Seven of the eigth completely lesioned cats developed motion-induced CTA, even though emesis was not consistently elicited by motion. These results suggest that there are multiple routes for inducing CTA and the emetic reflex, that CTA can form without eliciting emesis, and that CTA may be a sensitive measure of sub-emetic motion sickness.

Aethaperazinum,

DTIC Science & Technology

1979-11-02

patients who are not sensitive tc the effect /action of aminazine. PHARMAGOLOGICAL STUDY. Aethaperazinum - dihydrocdloride of 2-chloro- {[4-(8-hydroxyetnyl...that te new neuroplegic substance has the wide spectrum of activity, similar to the spectrum of the effect /action of aminazina. Page 147. All means of...the aminazine; some DOC = 791� PAGE 3 mans of the peripheral effect /action in aethaperazinus are expressed to a lesser degree. Anti-emetic effect

Immunocytochemical localization of glial fibrillary acidic protein (GFAP) in the area postrema of the cat - Light and electron microscopic study

NASA Technical Reports Server (NTRS)

Damelio, F. E.; Gibbs, M. A.; Mehler, W. R.; Eng, L. F.

1985-01-01

Glial fibrillary acidic protein (GFAP) was demonstrated in the cytoplasm and processes of ependymal cells and astroglial components of the area postrema of the cat. These observations differ from the findings in the ependyma of the ventricular cavities which are consistently negative for the protein. Since some studies have suggested sensory functions of the glial cells in this emetic chemoreceptor trigger zone, a careful consideration of morphological and biochemical attributes of these cells seems appropriate.

[Therapeutic use of Cannibis Sativa L. in Arab medicine].

PubMed

Lozano, I

1997-01-01

Arab scientists were various centuries ahead of our current knowledge of the curative power of hemp (Cannabis sativa L., Cannabaceae). Modern scientific literature ignores their contribution on the subject. We review in this paper the therapeutic uses of the plant in Arabic medicine from the 8th to the 18th century. Arab physicians knew and used its diuretic, anti-emetic, anti-epileptic, anti-inflammatory, pain-killing and antipyretic properties, among others.

Palonosetron as an anti-emetic and anti-nausea agent in oncology.

PubMed

Aapro, Matti S

2007-12-01

Palonosetron (Aloxi(®), Onicit(®), Paloxi(®)) is a second-generation 5-HT(3) receptor antagonist (RA) with an extended half-life of ~40 hours and high binding affinity for the 5-HT₃ receptor that is markedly different from other 5-HT(3) RAs. Phase III trials demonstrate that a single dose of palonosetron compared with traditional 5-HT₃ RAs is more effective in preventing chemotherapy-induced nausea and vomiting (CINV) during the first 24 hours following chemotherapy (acute CINV), and also exhibits prolonged efficacy to provide significantly better protection from CINV in the delayed and overall phases. This superior and extended protection from CINV conferred by palonosetron following a single intravenous dose before chemotherapy simplifies dosing schedules. Recent research has focused on optimization of palonosetron-based antiemetic regimens, particularly in combination with steroids and neurokinin-1 RAs. The available clinical data indicate high control rates for palonosetron, suggesting a synergistic potential for protection in patients scheduled to receive emetogenic drug regimens.

The Impact of Prophylactic Dexamethasone on Nausea and Vomiting after Thyroidectomy: A Systematic Review and Meta-Analysis

PubMed Central

Zou, Zhenhong; Jiang, Yuming; Xiao, Mingjia; Zhou, Ruiyao

2014-01-01

Background We carried out a systematic review and meta-analysis to evaluate the impact of prophylactic dexamethasone on post-operative nausea and vomiting (PONV), post-operative pain, and complications in patients undergoing thyroidectomy. Methods We searched Pubmed, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) that evaluated the prophylactic effect of dexamethasone versus placebo with or without other antiemetics for PONV in patients undergoing thyroidectomy. Meta-analyses were performed using RevMan 5.0 software. Results Thirteen RCTs that considered high quality evidence including 2,180 patients were analyzed. The meta-analysis demonstrated a significant decrease in the incidence of PONV (RR 0.52, 95% CI 0.43 to 0.63, P<0.00001), the need for rescue anti-emetics (RR 0.42, 95% CI 0.30 to 0.57, P<0.00001), post-operative pain scores (WMD –1.17, 95% CI –1.91 to –0.44, P = 0.002), and the need for rescue analgesics (RR 0.65, 95% CI 0.50–0.83, P = 0.0008) in patients receiving dexamethasone compared to placebo, with or without concomitant antiemetics. Dexamethasone 8–10mg had a significantly greater effect for reducing the incidence of PONV than dexamethasone 1.25–5mg. Dexamethasone was as effective as other anti-emetics for reducing PONV (RR 1.25, 95% CI 0.86–1.81, P = 0.24). A significantly higher level of blood glucose during the immediate post-operative period in patients receiving dexamethasone compared to controls was the only adverse event. Conclusions Prophylactic dexamethasone 8–10mg administered intravenously before induction of anesthesia should be recommended as a safe and effective strategy for reducing the incidence of PONV, the need for rescue anti-emetics, post-operative pain, and the need for rescue analgesia in thyroidectomy patients, except those that are pregnant, have diabetes mellitus, hyperglycemia, or contraindications for dexamethasone. More high quality trials are warranted to

Brain Activation by H1 Antihistamines Challenges Conventional View of Their Mechanism of Action in Motion Sickness: A Behavioral, c-Fos and Physiological Study in Suncus murinus (House Musk Shrew)

PubMed Central

Tu, Longlong; Lu, Zengbing; Dieser, Karolina; Schmitt, Christina; Chan, Sze Wa; Ngan, Man P.; Andrews, Paul L. R.; Nalivaiko, Eugene; Rudd, John A.

2017-01-01

Motion sickness occurs under a variety of circumstances and is common in the general population. It is usually associated with changes in gastric motility, and hypothermia, which are argued to be surrogate markers for nausea; there are also reports that respiratory function is affected. As laboratory rodents are incapable of vomiting, Suncus murinus was used to model motion sickness and to investigate changes in gastric myoelectric activity (GMA) and temperature homeostasis using radiotelemetry, whilst also simultaneously investigating changes in respiratory function using whole body plethysmography. The anti-emetic potential of the highly selective histamine H1 receptor antagonists, mepyramine (brain penetrant), and cetirizine (non-brain penetrant), along with the muscarinic receptor antagonist, scopolamine, were investigated in the present study. On isolated ileal segments from Suncus murinus, both mepyramine and cetirizine non-competitively antagonized the contractile action of histamine with pKb values of 7.5 and 8.4, respectively; scopolamine competitively antagonized the contractile action of acetylcholine with pA2 of 9.5. In responding animals, motion (1 Hz, 4 cm horizontal displacement, 10 min) increased the percentage of the power of bradygastria, and decreased the percentage power of normogastria whilst also causing hypothermia. Animals also exhibited an increase in respiratory rate and a reduction in tidal volume. Mepyramine (50 mg/kg, i.p.) and scopolamine (10 mg/kg, i.p.), but not cetirizine (10 mg/kg, i.p.), significantly antagonized motion-induced emesis but did not reverse the motion-induced disruptions of GMA, or hypothermia, or effects on respiration. Burst analysis of plethysmographic-derived waveforms showed mepyramine also had increased the inter-retch+vomit frequency, and emetic episode duration. Immunohistochemistry demonstrated that motion alone did not induce c-fos expression in the brain. Paradoxically, mepyramine increased c-fos in brain

Postdural puncture headache: a study with 256 Quincke needle.

PubMed

Singh, N Ratan; Singh, H Shanti

2010-02-01

The incidence of postdural puncture headache, its severity, time of onset and duration following spinal anaesthesia in female subjects using 25 gauge Quincke needles are discussed in this paper. Postdural puncture headache was seen in only 3% of the cases. The headache appeared mainly on the 1st postoperative day and was associated with nausea and vomiting in one case; and it disappeared by the 2nd to 3rd day following administration of mild analgesics and anti-emetics.

Military Dog Training Aids: Toxicity and Treatment

DTIC Science & Technology

1989-11-10

current literature may provide additional toxicity information. 7. Treatment Humans: Treatment of the rare case of acute overdose or toxic psychosis from...substitute for heroin and is fentanyl or one of it derivatives. 2. Chemical And Physical Properties Molecular wt. 369.42 Boiling pt. 272 0 C Melting pt...coaiscious, give gastric lavage or emetic. Treat with antidote, Narcan at 0.01 mg/kg IV, in massive overdose of heroin use up to 0.2 mg/kg. 8

Use of Gelatin Sponge Affects Postoperative Morbidity In Cesarean Section Patients.

PubMed

Özer, Alev; Köstü, Bülent

2017-03-04

BACKGROUND This study aimed to determine the effects of use of a local hemostatic gelatin sponge (GS) on postoperative morbidity in patients undergoing cesarean section (CS). MATERIAL AND METHODS The records of 318 patients who underwent CS surgery were retrospectively evaluated. Group 1 consisted of 59 patients with gelatin sponge (GS) applied, and Group 2 consisted of 259 patients with no GS applied. The groups were compared for time to the first flatus, nausea and vomiting, requirement for anti-emetic drugs, development of postoperative ileus, and the length of hospitalization. RESULTS The patients in Group 1 and Group 2 were statistically similar in mean age, gravida, parity, and body mass index (BMI) (p=0.352, p=0.275, p=0.458, and p=0.814, respectively). No significant difference was determined in the number of patients with nausea, vomiting, anti-emetic drug use, febrile morbidity, and postoperative ileus (p=0.063, p=0.436, p=328, p=0.632, and p=0.179, respectively). Time to the first flatus and length of hospitalization were significantly longer in Group 2 (p<0.001 and p<0.001, respectively). CONCLUSIONS Delay in recovery of bowel motility may be due to the local hypersensitivity reaction caused by GS and/or dislocation of this local hemostat. Women who receive gelatin sponge treatment during CS should be monitored closely for the recovery of postoperative intestinal motility.

Are evolutionary hypotheses for motion sickness "just-so" stories?

PubMed

Oman, Charles M

2012-01-01

Vertebrates have evolved rapidly conditionable nausea and vomiting reflexes mediated by gut and brainstem receptors, clearly as a defense against neurotoxin ingestion. In 1977 Treisman proposed that sensory orientation linkages to emetic centers evolved for the same reason, and that motion sickness was an accidental byproduct. It was an "adaptationist" explanation for motion sickness, since it assumed that evolution has shaped all phenotypic traits for survival advantage. Treisman's "poison" theory is plausible, and frequently cited as the accepted scientific explanation for motion sickness. However, alternative explanations have been proposed. The creation of hypotheses is an essential part of science - provided they are testable. This paper reviews the evidence for the Poison theory and several other adaptationist explanations. These hypotheses are certainly not "just-so stories", but supporting evidence is equivocal, and contradictory evidence exists Parsimony suggests an alternative "pluralistic" view: The vertebrate reticular formation maintains oxygenated blood flow to the brain, discriminates unexpected sensory stimuli- including postural disturbances, and detects and expels ingested neurotoxins. The three systems share neuroarchitectural elements but normally function independently. Brainstem sensory conflict neurons normally discriminate brief postural disturbances, but can be abnormally stimulated during prolonged passive transport (e.g. by boat, beginning about 150-200 generations ago). Sensory conflict signals cross couple into the neurotoxin expulsion and avoidance system, producing an arguably maladaptive emetic phenotype.

Antiemetic activity of volatile oil from Mentha spicata and Mentha × piperita in chemotherapy-induced nausea and vomiting

PubMed Central

Tayarani-Najaran, Z; Talasaz-Firoozi, E; Nasiri, R; Jalali, N; Hassanzadeh, MK

2013-01-01

Background: This study is aimed at determining the efficacy of Mentha spicata (M. spicata) and Mentha × piperita (M. × piperita) in preventing chemotherapy-induced nausea and vomiting (CINV). Methods: This was a randomised, double-blind clinical trial study. Prior to the study, patients were randomly assigned into four groups to receive M. spicata or M. × piperita. Statistical analysis included the χ2 test, relative risk, and Student’s t-test. Fifty courses were analysed for each group that met our eligibility criteria. The treatment and placebo groups applied essential oils of M. spicata, M. × piperita, or a placebo, while the control group continued with their previous antiemetic regimen. Patients or guardians recorded the number of emetic events, the intensity of nausea over 20 h of chemotherapy, as well as any possible adverse effects that occurred during this time. Results: There was a significant reduction in the intensity and number of emetic events in the first 24 h with M. spicata and M. × piperita in both treatment groups (p < 0.05) when compared with the control and no adverse effects were reported. The cost of treatment was also reduced when essential oils were used. Conclusion: M. spicata or M. × piperita essential oils are safe and effective for antiemetic treatment in patients, as well as being cost effective. PMID:23390455

Receptor-Selective Agonists Induce Emesis and Fos Expression in the Brain and Enteric Nervous System of the Least Shrew (Cryptotis parva)

PubMed Central

Ray, Andrew P.; Chebolu, Seetha; Darmani, Nissar A.

2009-01-01

Research on the mechanisms of emesis has implicated multiple neurotransmitters via both central (dorsal vagal complex) and peripheral (enteric neurons and enterochromaffin cells) anatomical substrates. Taking advantage of advances in receptor-specific agonists, and utilizing Fos expression as a functional activity marker, this study demonstrates a strong, but incomplete, overlap in anatomical substrates for a variety of emetogens. We used cisplatin and specific agonists to 5-HT3 serotonergic, D2/D3 dopaminergic, and NK1 tachykininergic receptors to induce vomiting in the least shrew (Cryptotis parva), and quantified the resulting Fos expression. The least shrew is a small mammal whose responses to emetic challenges are very similar to its human counterparts. In all cases, the enteric nervous system, nucleus of the solitary tract, and dorsal motor nucleus of the vagus demonstrated significantly increased Fos immunoreactivity (Fos-IR). However, Fos-IR induction was notably absent from the area postrema following the dopaminergic and NK1 receptor-specific agents. Two brain nuclei not usually discussed regarding emesis, the dorsal raphe nucleus and paraventricular thalamic nucleus, also demonstrated increased emesis-related Fos-IR. Taken together, these data suggest the dorsal vagal complex is part of a common pathway for a variety of distinct emetogens, but there are central emetic substrates, both medullary and diencephalic, that can be accessed without directly stimulating the area postrema. PMID:19699757

Comparison of the effects of sugammadex and neostigmine on postoperative nausea and vomiting.

PubMed

Yağan, Özgür; Taş, Nilay; Mutlu, Tuğçe; Hancı, Volkan

The aim of our study is to compare the effects of sugammadex and neostigmine, used for neuromuscular blockage antagonism, on postoperative nausea and vomiting (PONV). Our study was completed with 98 ASA I-II risk patients undergoing endotracheal intubation under general anesthesia. At the end of the surgery patients were randomly divided into two groups given 2mgkg -1 sugammadex (Group S) or 50μgkg -1 neostigmine plus 0.2mgkg -1 atropine (Group N). Monitoring and recording times were set as 1 hour postoperative and from 1-6, 6-12, and 12-24hours. The anti-emetic amounts administered were recorded. In the first hour postoperative 13 patients in Group N (27%) and 4 in Group S (8%) were observed to have nausea and/or vomiting and the difference was statistically significant (p=0.0016). During the 24 hours of monitoring there was no significant difference in the incidence and severity of PONV (p>0.05), however the number of patients given ondansetron for PONV treatment in Group N was statistically significantly higher than the number in Group S (16 in Group N, 6 in Group S, p<0.011). At the end of our study comparing neostigmine with sugammadex for neuromuscular blockage antagonism, we found use of sugammadex had lower incidence of PONV in the postoperative 1st hour and less anti-emetic use in 24 hours of monitoring. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Bacillus cereus and related species.

PubMed

Drobniewski, F A

1993-10-01

Bacillus cereus is a gram-positive aerobic or facultatively anaerobic spore-forming rod. It is a cause of food poisoning, which is frequently associated with the consumption of rice-based dishes. The organism produces an emetic or diarrheal syndrome induced by an emetic toxin and enterotoxin, respectively. Other toxins are produced during growth, including phospholipases, proteases, and hemolysins, one of which, cereolysin, is a thiol-activated hemolysin. These toxins may contribute to the pathogenicity of B. cereus in nongastrointestinal disease. B. cereus isolated from clinical material other than feces or vomitus was commonly dismissed as a contaminant, but increasingly it is being recognized as a species with pathogenic potential. It is now recognized as an infrequent cause of serious nongastrointestinal infection, particularly in drug addicts, the immunosuppressed, neonates, and postsurgical patients, especially when prosthetic implants such as ventricular shunts are inserted. Ocular infections are the commonest types of severe infection, including endophthalmitis, panophthalmitis, and keratitis, usually with the characteristic formation of corneal ring abscesses. Even with prompt surgical and antimicrobial agent treatment, enucleation of the eye and blindness are common sequelae. Septicemia, meningitis, endocarditis, osteomyelitis, and surgical and traumatic wound infections are other manifestations of severe disease. B. cereus produces beta-lactamases, unlike Bacillus anthracis, and so is resistant to beta-lactam antibiotics; it is usually susceptible to treatment with clindamycin, vancomycin, gentamicin, chloramphenicol, and erythromycin. Simultaneous therapy via multiple routes may be required.

Action of Bacopa monnieri to antagonize cisplatin-induced emesis in Suncus murinus (house musk shrew).

PubMed

Ullah, Ihsan; Subhan, Fazal; Lu, Zengbing; Chan, Sze Wa; Rudd, John A

2017-04-01

Bacopa monnieri (BM, family Scrophulariaceae) is used in several traditional systems of medicine for the management of epilepsy, depression, neuropathic pain, sleep disorders and memory deficits. The present study investigated the potential of BM methanol (BM-MetFr) and BM n-butanol fractions (BM-ButFr) to reduce chemotherapy-induced emesis in Suncus murinus (house musk shrew). Cisplatin (30 mg/kg, i.p.) reliably induced retching and/or vomiting over a 2 day period. BM-MetFr (10-40 mg/kg, s.c.) and BM-ButFr (5-20 mg/kg, s.c.) antagonized the retching and/or vomiting response by ∼59.4% (p < 0.05) and 78.9% (p < 0.05), respectively, while the 5-HT 3 receptor antagonist, palonosetron (0.5 mg/kg, s.c.), reduced the response by ∼71% (p < 0.05). The free radical scavenger/antioxidant, N-(2-mercaptopropionyl)-glycine (30-300 mg/kg, s.c.) reduced the retching and/or vomiting response occurring on day one non-significantly by 44% (p > 0.05). In conclusion, the n-butanol fractions of BM have anti-emetic activity comparable with palonosetron and MPG. BM may be useful alone or in combination with other anti-emetic drugs for the treatment of chemotherapy-induced emesis in man. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Effects of valproic acid and magnesium sulphate on rocuronium requirement in patients undergoing craniotomy for cerebrovascular surgery.

PubMed

Kim, M-H; Hwang, J-W; Jeon, Y-T; Do, S-H

2012-09-01

Many anti-epileptics cause resistance to non-depolarizing neuromuscular blocking agents, but this has not been reported for valproic acid (VPA). We hypothesized that VPA would increase the rocuronium requirement and that magnesium sulphate (MgSO(4)) may reduce this increase. Fifty-five patients undergoing cerebrovascular surgeries were studied. Subjects were allocated into three groups at a 1:1:1 ratio: Groups VM, VC, and C. Groups VM and VC were given VPA premedication; Group C was not. A rocuronium injection (0.6 mg kg(-1) i.v.) was administered to Group VM, followed by MgSO(4) as a 50 mg kg(-1) i.v. bolus and 15 mg kg(-1) h(-1) infusion. The same volume of 0.9% saline was administered to the other groups. Supplementary rocuronium (0.15 mg kg(-1)) was given whenever the train-of-four count reached 2. Rocuronium requirements (primary outcome), mean arterial pressure (MAP), heart rate (HR), nausea, vomiting, shivering, and use of anti-emetics and nicardipine were compared. Group VC showed the highest rocuronium requirement [mg kg(-1) h(-1): 0.47 (0.08) vs 0.33 (0.12) (Group C), 0.31 (0.07) (Group VM); P<0.001]. MAP, intraoperative HR, nausea, vomiting, shivering, and use of anti-emetics and nicardipine were not significantly different among the groups. Postoperative HR was lower in Group VM than in Group VC. VPA increased the rocuronium requirement, and MgSO(4) infusion attenuated this increase.

Antiemetic effects of a potent and selective neurokinin-1 receptor antagonist, FK886, on cisplatin- and apomorphine-induced emesis in dogs.

PubMed

Furukawa, Takako Yoshino; Nakayama, Hiroe; Kikuchi, Aya; Imazumi, Katsunori; Yamakuni, Hisashi; Sogabe, Hajime; Yamasaki, Sachiko; Takeshita, Koji; Matsuo, Masahiko; Manda, Toshitaka; Uchida, Wataru

2013-01-01

The antiemetic properties of a novel neurokinin-1 (NK1) receptor antagonist, FK886 ([3,5-bis(trifluoromethyl)phenyl][(2R)-2-(3-hydroxy-4-methylbenzyl)-4-{2-[(2S)-2-(methoxymethyl)morpholin-4-yl]ethyl}piperazin-1-yl]methanone dihydrochloride), were studied in dog models of cisplatin- and apomorphine-induced emesis. Intravenously administered FK886 (0.32-1 mg/kg) significantly inhibited cisplatin-induced acute emesis during the 5-h observation period. Nearly complete inhibition was observed at 1 mg/kg. At an equivalent dose range, orally administered FK886 also significantly inhibited emesis, indicating good oral absorption. Similarly, FK886 inhibited apomorphine-induced emetic responses effectively following both intravenous and oral administration. The effects were long lasting, with 1.6 mg/kg of FK886 completely blocking apomorphine-induced retching and vomiting after a 12-h pretreatment period. Furthermore, FK886 showed rapid onset of antiemetic activity after oral administration. At doses of 0.32 mg/kg or more, a pretreatment time of 0.5 h was sufficient for complete inhibition of apomorphine-induced emetic responses. This fast onset after oral administration was supported by pharmacokinetic data, which demonstrated plasma levels of FK886 after oral administration reached levels similar to those 30 min after intravenous administration. These results suggest that FK886 has excellent antiemetic properties in dogs, and that its rapid-onset and long-lasting properties might make it a promising antiemetic agent.

Cereulide production by Bacillus weihenstephanensis strains during growth at different pH values and temperatures.

PubMed

Guérin, Alizée; Rønning, Helene Thorsen; Dargaignaratz, Claire; Clavel, Thierry; Broussolle, Véronique; Mahillon, Jacques; Granum, Per Einar; Nguyen-The, Christophe

2017-08-01

Besides Bacillus cereus, some strains of the psychrotolerant, potentially foodborne pathogen Bacillus weihenstephanensis can produce the emetic toxine (cereulide). This toxin is a heat- and acid-stable cyclic dodecadepsipeptide that causes food intoxication with vomiting. However, some severe clinical cases with lethal outcomes have been described. If cereulide can be produced during refrigerated storage, it will not be inactivated by reheating food, representing an important risk of food intoxication for consumers. In this paper, we determined the capacity of the B. weihenstephanensis strains BtB2-4 and MC67 to grow and produce cereulide on agar media at temperatures from 8 °C to 25 °C and at a pH from 5.4 to 7.0. At 8 °C, strain BtB2-4 produced quantifiable amounts of cereulide, whereas the limit of detection was reached for strain MC67. For BtB2-4, cereulide production increased 5-fold between 8 °C and 10-15 °C and by more than 100-fold between 15 °C and 25 °C. At temperatures of 10 °C and higher, cereulide concentrations were within the range of those reported by previous works in foods implicated in emetic poisoning. At 25 °C, decreasing the pH to 5.4 reduced cereulide production by strain BtB2-4 by at least 20-fold. Copyright © 2017 Elsevier Ltd. All rights reserved.

Medicinal cannabis: rational guidelines for dosing.

PubMed

Carter, Gregory T; Weydt, Patrick; Kyashna-Tocha, Muraco; Abrams, Donald I

2004-05-01

The medicinal value of cannabis (marijuana) is well documented in the medical literature. Cannabinoids, the active ingredients in cannabis, have many distinct pharmacological properties. These include analgesic, anti-emetic, anti-oxidative, neuroprotective and anti-inflammatory activity, as well as modulation of glial cells and tumor growth regulation. Concurrent with all these advances in the understanding of the physiological and pharmacological mechanisms of cannabis, there is a strong need for developing rational guidelines for dosing. This paper will review the known chemistry and pharmacology of cannabis and, on that basis, discuss rational guidelines for dosing.

Isolation of Bacillus cereus Group from the Fecal Material of Endangered Wood Turtles.

PubMed

Nfor, Nancy Ngvumbo; Lapin, Carly N; McLaughlin, Richard William

2015-10-01

Members of the Bacillus cereus group are opportunistic human pathogens. They can be found in a broad range of foods. Diarrheal food poisoning and/or emetic type syndromes can result from eating contaminated food. In this study, seven B. cereus group members were isolated from the fecal material of Wood Turtles (Glyptemys insculpta). The isolates were then assessed for the presence of enterotoxin genes (nheA, entFM, hblC, and cytK) using PCR. The most prevalent is the nonhemolytic enterotoxin gene which was found in all seven isolates.

Nevasic audio program for the prevention of chemotherapy induced nausea and vomiting: A feasibility study using a randomized controlled trial design.

PubMed

Moradian, Saeed; Walshe, Catherine; Shahidsales, Soodabeh; Ghavam Nasiri, Mohammad Reza; Pilling, Mark; Molassiotis, Alexander

2015-06-01

Pharmacological therapy is only partially effective in preventing or treating chemotherapy induced nausea and vomiting (CINV). Therefore, exploring the complementary role of non-pharmacological approaches used in addition to pharmacological agents is important. Nevasic uses specially constructed audio signals hypothesized to generate an antiemetic reaction. The aim of this study was to examine the feasibility of conducting a randomized controlled trial (RCT) to evaluate the effectiveness of Nevasic to control CINV. A mixed methods design incorporating an RCT and focus group interviews. For the RCT, female breast cancer patients were randomized to receive either Nevasic plus usual care, music plus usual care, or usual care only. Data were analysed using descriptive statistics and linear mixed-effects models. Five focus group interviews were conducted to obtain participants' views regarding the acceptability of the interventions in the trial. 99 participants were recruited to the RCT and 15 participated in focus group interviews. Recruitment targets were achieved. Issues of Nevasic acceptability were highlighted as weaknesses of the program. This study did not detect any evidence for the effectiveness of Nevasic; however, the results showed statistically significant less use of anti-emetics (p = 0.003) and borderline non-significant improvement in quality of life (p = 0.06). Conducting a non-pharmacological intervention using such an audio program is feasible, although difficulties and limitations exist with its use. Further studies are required to investigate the effectiveness of Nevasic from perspectives such as anti-emetic use, as well as its overall effect on the levels of nausea and vomiting. Copyright © 2014 Elsevier Ltd. All rights reserved.

Responses of neurons in the caudal medullary lateral tegmental field to visceral inputs and vestibular stimulation in vertical planes

PubMed Central

Moy, Jennifer D.; Miller, Daniel J.; Catanzaro, Michael F.; Boyle, Bret M.; Ogburn, Sarah W.; Cotter, Lucy A.; McCall, Andrew A.

2012-01-01

The dorsolateral reticular formation of the caudal medulla, or the lateral tegmental field (LTF), has been classified as the brain's “vomiting center”, as well as an important region in regulating sympathetic outflow. We examined the responses of LTF neurons in cats to rotations of the body that activate vestibular receptors, as well as to stimulation of baroreceptors (through mechanical stretch of the carotid sinus) and gastrointestinal receptors (through the intragastric administration of the emetic compound copper sulfate). Approximately half of the LTF neurons exhibited graviceptive responses to vestibular stimulation, similar to primary afferents innervating otolith organs. The other half of the neurons had complex responses, including spatiotemporal convergence behavior, suggesting that they received convergent inputs from a variety of vestibular receptors. Neurons that received gastrointestinal and baroreceptor inputs had similar complex responses to vestibular stimulation; such responses are expected for neurons that contribute to the generation of motion sickness. LTF units with convergent baroreceptor and vestibular inputs may participate in producing the cardiovascular system components of motion sickness, such as the changes in skin blood flow that result in pallor. The administration of copper sulfate often modulated the gain of responses of LTF neurons to vestibular stimulation, particularly for units whose spontaneous firing rate was altered by infusion of drug (median of 459%). The present results raise the prospect that emetic signals from the gastrointestinal tract modify the processing of vestibular inputs by LTF neurons, thereby affecting the probability that vomiting will occur as a consequence of motion sickness. PMID:22955058

Acupressure bands do not improve chemotherapy-induced nausea control in pediatric patients receiving highly emetogenic chemotherapy: A single-blinded, randomized controlled trial.

PubMed

Dupuis, L Lee; Kelly, Kara M; Krischer, Jeffrey P; Langevin, Anne-Marie; Tamura, Roy N; Xu, Ping; Chen, Lu; Kolb, E Anders; Ullrich, Nicole J; Sahler, Olle Jane Z; Hendershot, Eleanor; Stratton, Ann; Sung, Lillian; McLean, Thomas W

2018-03-15

Chemotherapy-induced nausea and vomiting remain common, distressing side effects of chemotherapy. It has been reported that acupressure prevents chemotherapy-induced nausea in adults, but it has not been well studied in children. In this multicenter, prospective, randomized, single-blind, sham-controlled trial, the authors compared acute-phase nausea severity in patients ages 4 to 18 years who were receiving highly emetic chemotherapy using standard antiemetic agents combined with acupressure wrist bands, the most common type of acupressure, versus sham bands. Patients wore acupressure or sham bands continuously on each day of chemotherapy and for up to 7 days afterward. Chemotherapy-induced nausea severity in the delayed phase and chemotherapy-induced vomiting control in the acute and delayed phases also were compared. Of the 187 patients randomized, 165 contributed nausea severity assessments during the acute phase. Acupressure bands did not reduce the severity of chemotherapy-induced nausea in the acute phase (odds ratio [OR], 1.33; 95% confidence limits, 0.89-2.00, in which an OR <1.00 favored acupressure) or in the delayed phase (OR, 1.23; 95% CL, 0.75-2.01). Furthermore, acupressure bands did not improve daily vomiting control during the acute phase (OR, 1.57; 95% CL, 0.95-2.59) or the delayed phase (OR, 0.84; 95% CL, 0.45-1.58). No serious adverse events were reported. Acupressure bands were safe but did not improve chemotherapy-induced nausea or vomiting in pediatric patients who were receiving highly emetic chemotherapy. Cancer 2018;124:1188-96. © 2017 American Cancer Society. © 2017 American Cancer Society.

Intra-abdominal saline irrigation at cesarean section: a systematic review and meta-analysis.

PubMed

Eke, Ahizechukwu Chigoziem; Shukr, Ghadear Hussein; Chaalan, Tina Taissir; Nashif, Sereen Khaled; Eleje, George Uchenna

2016-01-01

The aim of this study was to examine the evidence guiding intraoperative saline irrigation at cesarean sections. We searched "cesarean sections", "pregnancy", "saline irrigation" and "randomized clinical trials" in ClinicalTrials.gov, the Cochrane Central Register of Controlled Trials, AJOL, MEDLINE, LILACS and CINAHL from inception of each database to April 2015. The primary outcomes were predefined as intraoperative nausea and emesis. The pooled results were reported as relative risk (RR) with 95% confidence interval (95% CI). Three randomized trials including 862 women were analyzed. Intraoperative saline irrigation was associated with a 68% increased risk of developing intraoperative nausea (RR = 1.68, 95% CI 1.36-2.06), 70% increased risk of developing intraoperative emesis (RR = 1.70, 95% CI 1.28-2.25), 92% increased risk of developing post-operative nausea and 84% increased risk of using anti-emetics post-operatively (RR = 1.84, 95% CI 0.21-2.78) when compared with controls. There were no significant differences between intraoperative saline irrigation and no treatment for post-operative emesis (RR = 1.65, 95% CI 0.74-3.67), estimated blood loss, time to return of gastrointestinal function, postpartum endometritis (RR = 0.95, 95% CI 0.64-1.40), urinary tract infection and wound infection. Intraoperative saline irrigation at cesarean delivery increases intraoperative and post-operative nausea, requiring increasing use of anti-emetics without significant reduction in infectious, intraoperative and postpartum complications. Routine abdominal irrigation at cesarean section is not supported by current data.

Treating nausea and vomiting in palliative care: a review

PubMed Central

Glare, Paul; Miller, Jeanna; Nikolova, Tanya; Tickoo, Roma

2011-01-01

Nausea and vomiting are portrayed in the specialist palliative care literature as common and distressing symptoms affecting the majority of patients with advanced cancer and other life-limiting illnesses. However, recent surveys indicate that these symptoms may be less common and bothersome than has previously been reported. The standard palliative care approach to the assessment and treatment of nausea and vomiting is based on determining the cause and then relating this back to the “emetic pathway” before prescribing drugs such as dopamine antagonists, antihistamines, and anticholinergic agents which block neurotransmitters at different sites along the pathway. However, the evidence base for the effectiveness of this approach is meager, and may be in part because relevance of the neuropharmacology of the emetic pathway to palliative care patients is limited. Many palliative care patients are over the age of 65 years, making these agents difficult to use. Greater awareness of drug interactions and QTc prolongation are emerging concerns for all age groups. The selective serotonin receptor antagonists are the safest antiemetics, but are not used first-line in many countries because there is very little scientific rationale or clinical evidence to support their use outside the licensed indications. Cannabinoids may have an increasing role. Advances in interventional gastroenterology are increasing the options for nonpharmacological management. Despite these emerging issues, the approach to nausea and vomiting developed within palliative medicine over the past 40 years remains relevant. It advocates careful clinical evaluation of the symptom and the person suffering it, and an understanding of the clinical pharmacology of medicines that are available for palliating them. PMID:21966219

Atmospheric oxygen and other conditions affecting the production of cereulide by Bacillus cereus in food.

PubMed

Jääskeläinen, E L; Häggblom, M M; Andersson, M A; Salkinoja-Salonen, M S

2004-10-01

Factors influencing the production of cereulide, the emetic toxin of Bacillus cereus in food and laboratory media were investigated, using liquid chromatography-ion trap mass spectrometry and sperm motility inhibition bioassay for detection and quantitation. Oxygen was essential for production of the emetic toxin by B. cereus. When beans, rice or tryptic soy broth were inoculated with cereulide producing strains B203, B116 (recent food isolates) or the strain F-4810/72, high amounts (2 to 7 microg ml(-1) or g(-1) wet wt) of cereulide accumulated during 4-day storage at room temperature. In parallel cultures and foods, stored under nitrogen atmosphere (> 99.5% N2), less than 0.05 microg of cereulide ml(-1) or g(-1) wet wt accumulated. The outcome of the bioassay matched that of the chemical assay, with no indication of interference by substances in the rice or beans. Boiling for 20 to 30 min did not inactivate cereulide or cereulide producing strains in rice or the beans. Adding l-leucine and l-valine (0.3 g l(-1)) stimulated cereulide production 10- to 20-fold in R2A and in rice water agar. When the B. cereus strains were grown on agar media under permissive conditions (air, room temperature), cereulide was produced overnight with little or no increase when the incubation was extended to 4 days. In broth culture, the production of cereulide started later than 16-24 h. Anoxic storage prevented cereulide production also when the amino acids had been supplied. Packaging with modified atmosphere low in oxygen may thus be used to reduce the risk of cereulide formation during storage of food. Copyright 2004 Elsevier B.V.

The lesser of two adverse reactions.

PubMed

Chakraborti, Chayan; Egan, John

2010-01-01

Fundamental to complex systems are interconnected processes involved in providing high-quality patient care. A case study and a root cause analysis (RCA) illustrate a patient safety effort with unintended consequences. A 38-year-old woman presented to the hospital for odynophagia and vomiting. The patient developed Mobitz type 2, second-degree heart block temporally associated with the administration of intravenous ondansetron. RESPONSE TO THE EVENT: An Ishikawa, or fishbone, diagram conducted to enumerate potential contributing factors indicated that a key factor appeared to be an institutional restriction against using intravenous (i.v.) promethazine, which resulted in ondansetron being the only readily available i.v. anti-emetic on formulary. The anesthesia department requested that i.v. promethazine be removed from all operating and recovery room automated medication dispensing machines. The pharmacy department, given the realization that individual departments were taking independent action regarding promethazine, discussed the matter with the medical director, who issued a memo banning the use of i.v. promethazine. An institutional ban on i.v. anti-emetics such as promethazine may have resulted in an increase in the use of ondansetron and contributed to this adverse reaction. The reason to restrict promethazine is not well reported in the literature. In limiting the use of promethazine for patient safety concerns, the inadvertent increase in adverse reactions of the alternative medication, ondansetron, may have been overlooked. The resultant RCA underscores the need for careful cataloguing of adverse medication effects. Stakeholders should anticipate as many "downstream effects" of quality and patient safety improvements as possible. Comprehensive reporting of adverse medication effects will augment the emerging science of patient safety.

8-OH-DPAT suppresses vomiting in the cat elicited by motion, cisplatin or xylazine

NASA Technical Reports Server (NTRS)

Lucot, James B.; Crampton, George H.

1989-01-01

Vomiting was suppressed in cats pretreated with 8-OH-DPAT and then challenged with an emetic stimulus; motion, xylazine or cisplatin. The antiemetic effect is likely due to stimulation of postsynaptic serotonin-1A receptors. The most parsimonious explanation is that it acts at a convergent structure, presumably at or near the vomiting center. If so, 8-OH-DPAT may block emesis elicited by virtually any other stimulus. A supplementary experiment revealed that lorazepam suppressed motion sickness at a dose that produced ataxia, but did not suppress xylazine-induced emesis. These results do not support the possibility that the antiemetic effects of 8-OH-DPAT were the result of anxiolytic activity.

Creating Centralized Reporting for Microsoft Host Protection Technologies:The Enhanced Mitigation Experience Toolkit (EMET)

DTIC Science & Technology

2016-08-11

INSTITUTE | CARNEGIE MELLON UNIVERSITY [Distribution Statement A] This material has been approved for public release and unlimited distribution...Copyright 2016 Carnegie Mellon University This material is based upon work funded and supported by the Department of Defense under Contract No. FA8721...05-C-0003 with Carnegie Mellon University for the operation of the Software Engineer- ing Institute, a federally funded research and development

Neural Connectivity and Immunocytochemical Studies of Anatomical Sites Related to Nauseogenic and Emetic Reflexes

NASA Technical Reports Server (NTRS)

Fox, Robert A. (Principal Investigator)

1992-01-01

The studies conducted in this research project examined several aspects of neuroanatomical structures and neurochemical processes related to motion sickness in animal models. A principle objective of these studies was to investigate neurochemical changes in the central nervous system that are related to motion sickness with the objective of defining neural mechanisms important to this malady. For purposes of exposition, the studies and research finding have been classified into five categories. These are: immunoreactivity in the brainstem, vasopressin effects, lesion studies of area postrema, role of the vagus nerve, and central nervous system structure related to adaptation to microgravity.

Assessment of the relationship between adherence with antiemetic drug therapy and control of nausea and vomiting in breast cancer patients receiving anthracycline-based chemotherapy.

PubMed

Chan, Alexandre; Low, Xiu Hui; Yap, Kevin Yi-Lwern

2012-06-01

There are little prevalence data in the literature on nonadherence to outpatient antiemetic regimens for prophylaxis of chemotherapy-induced nausea and vomiting (CINV). It is unclear whether adherence with outpatient antiemetic regimens is associated with better CINV control. Our previous survey research supports the work of clinical pharmacists in collaborative practice with medical oncologists in improving adherence with antiemetic therapy in women undergoing highly emetic chemotherapy for breast cancer. To (a) evaluate the impact of adherence to delayed antiemetics (days 2-4 following anthracycline-based chemotherapy) on CINV control in breast cancer patients after anthracycline-based chemotherapy and (b) identify patient-related factors associated with nonadherence to delayed antiemetics. A single-center, prospective, observational study was conducted from December 2006 to January 2011 in breast cancer patients receiving anthracycline-based chemotherapy (doxorubicin or epirubicin) and antiemetics at the National Cancer Centre Singapore (NCCS), the largest ambulatory cancer center in Singapore. Included patients were aged 21 years or older with confirmed diagnoses of breast cancer and receiving anthracycline-containing chemotherapy with antiemetics. Patients were excluded if they (a) were diagnosed with intestinal obstruction or received concurrent radiotherapy that predisposed them to nausea and vomiting, (b) had vomited in the 24 hours preceding chemotherapy, or (c) had brain metastases that would impair their judgment. Patients documented in a standardized diary their emesis events, severity of nausea, use of rescue therapy with metoclopramide, and compliance with dose instructions for antiemetic drug therapy for 5 days: day 1 was the day of chemotherapy and first day of antiemetic therapy, and day 5 was the day after completion of delayed antiemetic therapy (days 2-4). Three definitions were used to describe the CINV outcomes: (a) complete response (no

UTILIZATION OF THE LEAST SHREW AS A RAPID AND SELECTIVE SCREENING MODEL FOR THE ANTIEMETIC POTENTIAL AND BRAIN PENETRATION OF SUBSTANCE P AND NK1 RECEPTOR ANTAGONISTS

PubMed Central

Darmani, Nissar A.; Wang, Yaozhi; Abad, Joseph; Ray, Andrew P.; Thrush, Gerald R.; Ramirez, Juan

2008-01-01

Substance P (SP) is thought to play a cardinal role in emesis via the activation of central tachykinin NK1 receptors during the delayed phase of vomiting produced by chemotherapeutics. Although the existing supportive evidence is significant, due to lack of an appropriate animal model, the evidence is indirect. As yet, no study has confirmed that emesis produced by SP or a selective NK1 receptor agonist is sensitive to brain penetrating antagonists of either NK1, NK2, or NK3 receptors. The goals of this investigation were to demonstrate: 1) whether intraperitoneal (i.p.) administration of either SP, a brain penetrating (GR73632) or non-penetrating (e.g. SarMet – SP) NK1 receptor agonist, an NK2 receptor agonist (GR64349), or an NK3 receptor agonist (Pro7-NKB), would induce vomiting and/or scratching in the least shrew (Cryptotis parva) in a dose-dependent manner; and whether these effects are sensitive to the above selective receptor antagonists; 2) whether an exogenous emetic dose of SP (50 mg/kg, i.p.) can penetrate into the shrew brain stem and frontal cortex; 3) whether GR73632 (2.5 mg/kg, i.p.)-induced activation of NK1 receptors increases Fos-measured neuronal activity in the neurons of both brain stem emetic nuclei and the enteric nervous system of the gut; and 4) whether selective ablation of peripheral NK1 receptors can affect emesis produced by GR73632. The results clearly demonstrated that while SP produced vomiting only, GR73632 caused both emesis and scratching behavior dose-dependently in shrews, and these effects were sensitive to NK1-, but not NK2- or NK3-receptor antagonists. Neither the selective, non-penetrating NK1 receptor agonists, nor the selective NK2- or NK3-receptor agonists, caused a significant dose-dependent behavioral effect. An emetic dose of SP selectively and rapidly penetrated the brain stem but not the frontal cortex. Systemic GR73632 increased Fos expression in the enteric nerve plexi, the medial subnucleus of nucleus tractus

Thapsigargin-induced activation of Ca(2+)-CaMKII-ERK in brainstem contributes to substance P release and induction of emesis in the least shrew.

PubMed

Zhong, Weixia; Chebolu, Seetha; Darmani, Nissar A

2016-04-01

Cytoplasmic calcium (Ca(2+)) mobilization has been proposed to be an important factor in the induction of emesis. The selective sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitor thapsigargin, is known to deplete intracellular Ca(2+) stores, which consequently evokes extracellular Ca(2+) entry through cell membrane-associated channels, accompanied by a prominent rise in cytosolic Ca(2+). A pro-drug form of thapsigargin is currently under clinical trial as a targeted cancer chemotherapeutic. We envisioned that the intracellular effects of thapsigargin could cause emesis and planned to investigate its mechanisms of emetic action. Indeed, thapsigargin did induce vomiting in the least shrew in a dose-dependent and bell-shaped manner, with maximal efficacy (100%) at 0.5 mg/kg (i.p.). Thapsigargin (0.5 mg/kg) also caused increases in c-Fos immunoreactivity in the brainstem emetic nuclei including the area postrema (AP), nucleus tractus solitarius (NTS) and dorsal motor nucleus of the vagus (DMNX), as well as enhancement of substance P (SP) immunoreactivity in DMNX. In addition, thapsigargin (0.5 mg/kg, i.p.) led to vomit-associated and time-dependent increases in phosphorylation of Ca(2+)/calmodulin kinase IIα (CaMKIIα) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) in the brainstem. We then explored the suppressive potential of diverse chemicals against thapsigargin-evoked emesis including antagonists of: i) neurokinin-1 receptors (netupitant), ii) the type 3 serotonin receptors (palonosetron), iii) store-operated Ca(2+) entry (YM-58483), iv) L-type Ca(2+) channels (nifedipine), and v) SER Ca(2+)-release channels inositol trisphosphate (IP3Rs) (2-APB)-, and ryanodine (RyRs) (dantrolene)-receptors. In addition, the antiemetic potential of inhibitors of CaMKII (KN93) and ERK1/2 (PD98059) were investigated. All tested antagonists/blockers attenuated emetic parameters to varying degrees except palonosetron, however a combination of non

Signals for nausea and emesis: Implications for models of upper gastrointestinal diseases

PubMed Central

Andrews, Paul L.R.; Horn, Charles C.

2009-01-01

Nausea and vomiting are amongst the most common symptoms encountered in medicine as either symptoms of diseases or side effects of treatments. In a more biological setting they are also important components of an organism’s defences against ingested toxins. Identification of treatments for nausea and vomiting and reduction of emetic liability of new therapies has largely relied on the use of animal models, and although such models have proven invaluable in identification of the anti-emetic effects of both 5-hydroxytryptamine3 and neurokinin1 receptor antagonists selection of appropriate models is still a matter of debate. The present paper focuses on a number of controversial issues and gaps in our knowledge in the study of the physiology of nausea and vomiting including: The choice of species for the study of emesis and the underlying behavioural (e.g. neophobia), anatomical (e.g. elongated, narrow abdominal oesophagus with reduced ability to shorten) and physiological (e.g. brainstem circuitry) mechanisms that explain the lack of a vomiting reflex in certain species (e.g. rats); The choice of response to measure (emesis[retching and vomiting], conditioned flavour avoidance or aversion, ingestion of clay[pica], plasma hormone levels[e.g. vasopressin], gastric dysrhythmias) and the relationship of these responses to those observed in humans and especially to the sensation of nausea; The stimulus coding of nausea and emesis by abdominal visceral afferents and especially the vagus—how do the afferents encode information for normal postprandial sensations, nausea and finally vomiting?; Understanding the central processing of signals for nausea and vomiting is particularly problematic in the light of observations that vomiting is more readily amenable to pharmacological treatment than is nausea, despite the assumption that nausea represents “low” intensity activation of pathways that can evoke vomiting when stimulated more intensely. PMID:16556512

The carboxyl-terminal region of staphylococcal enterotoxin type A is required for a fully active molecule.

PubMed Central

Hufnagle, W O; Tremaine, M T; Betley, M J

1991-01-01

Staphylococcal enterotoxin type A (SEA) gene (sea+) mutations were constructed by exonuclease III digestion or cassette mutagenesis. Five different sea mutations that had 1, 3, 7, 39, and 65 codons deleted from the 3' end of sea+ were identified and confirmed by restriction enzyme and nucleotide sequence analyses. Each of these sea mutations was constructed in Escherichia coli and transferred to Staphylococcus aureus by using the plasmid vector pC194. Culture supernatants from the parent S. aureus strain that lacked an enterotoxin gene (negative controls) and from derivatives that contained either sea+ (positive control) or a sea mutation were examined for in vitro sensitivity to degradation by monkey stomach lavage fluid, the ability to cause emesis when administered by an intragastric route to rhesus monkeys, and the ability to induce T-cell proliferation and by Western immunoblot analysis and a gel double-diffusion assay with polyclonal antibodies prepared against SEA. Altered SEAs corresponding to the predicted sizes were visualized by Western blot analysis of culture supernatants for each of the staphylococcal derivatives that contained a sea mutation. The altered SEA that lacked the C-terminal amino acid residue behaved like SEA in all of the assays performed. The altered SEA that lacked the three C-terminal residues of SEA caused T-cell proliferation but was not emetic; this altered SEA was degraded in vitro by monkey stomach lavage fluid and did not reach in the gel double diffusion assay. Altered SEAs that lacked 7, 39, or 65 carboxyl-terminal residues were degraded by stomach lavage fluid in vitro, did not produce an emetic response, and did not induce T-cell proliferation or form a visible reaction in the gel double-diffusion assay. Images PMID:1903773

Effect of olanzapine for breast cancer patients resistant to triplet antiemetic therapy with nausea due to anthracycline-containing adjuvant chemotherapy.

PubMed

Sato, Junya; Kashiwaba, Masahiro; Komatsu, Hideaki; Ishida, Kazushige; Nihei, Satoru; Kudo, Kenzo

2016-05-01

Triplet antiemetic therapy with neurokinin 1 receptor blocker, 5-hydroxytryptamine receptor blocker and steroids is commonly used in patients who are highly emetic after chemotherapy. However, an alternative antiemetic therapy for patients who are resistant to triplet antiemetic therapy is not established. Olanzapine is recommended in the guidelines as an optional antiemetic drug. However, the effectiveness of adding olanzapine to triplet antiemetic therapy is unknown. In this study, the effectiveness and safety of adding olanzapine to triplet antiemetic therapy with aprepitant, palonosetron and dexamethasone as highly emetic anthracycline-containing adjuvant chemotherapy for primary breast cancer patients were prospectively investigated. Forty-five patients with breast cancer who experienced >Grade 1 nausea or any vomiting after the first cycle of chemotherapy using both epirubicin and cyclophosphamide were included. Low-dose olanzapine (2.5 mg/day) was administered orally from the first day of chemotherapy for 4 days, and the number of episodes of vomiting, scale of nausea, dietary intake and somnolence were compared with the symptoms after the first cycle. As the primary endpoint, the nausea grade was significantly improved by adding olanzapine (P < 0.05). As the secondary endpoints, mean nausea scale (3.2→1.9, Day 1; 3→1.3-1, Days 2-6) and dietary intake (33.6→53.8%, Day 1; 42.0→60.7-78.1%, Days 2-6) were improved by adding olanzapine. Only four patients withdrew due to somnolence and/or dizziness. This study demonstrated the effectiveness and tolerability of adding low-dose olanzapine for patients with insufficient nausea relief with triplet antiemetic therapy consisting of palonosetron, steroid and aprepitant. Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

A comparative analysis of the potential of cannabinoids and ondansetron to suppress cisplatin-induced emesis in the Suncus murinus (house musk shrew).

PubMed

Kwiatkowska, Magdalena; Parker, Linda A; Burton, Page; Mechoulam, Raphael

2004-07-01

The 5-HT3 antagonist, ondansetron (OND), and the cannabinoid, delta9-tetrahydrocannabinol (delta9-THC), have been shown to interfere with emesis; however, their relative and/or combined effectiveness in suppressing vomiting produced by the chemotherapeutic agent, cisplatin, is unknown. To evaluate the potential of: 1) a broad range of doses of delta9-THC and OND to prevent cisplatin-induced vomiting and retching in the Suncus murinus (house musk shrew), 2) combined treatment with ineffective individual doses of delta9-THC and OND to prevent cisplatin-induced vomiting and retching, 3) the CB1 receptor antagonist, SR141716, to reverse the antiemetic effects of OND, and 4) cannabidiol (CBD), the principal non-psychoactive component of marijuana, to reverse cisplatin-induced vomiting in the shrew. Shrews were injected with various doses of OND (0.02-6.0 mg/kg), delta9-THC (1.25-10 mg/kg) and a combination of ineffective doses of each (0.02 mg/kg OND+1.25 mg/kg delta9-THC) prior to being injected with cisplatin (20 mg/kg) which induces vomiting. Shrews were also injected with CBD (5 mg/kg and 40 mg/kg) prior to an injection of cisplatin. OND and delta9-THC both dose-dependently suppressed cisplatin-induced vomiting and retching. Furthermore, a combined pretreatment of doses of the two drugs that were ineffective alone completely suppressed vomiting and retching. CBD produced a biphasic effect, suppressing vomiting at 5 mg/kg and potentiating it at 40 mg/kg. A low dose of the non-intoxicating cannabinoid CBD may be an effective anti-emetic treatment and combined doses of OND and delta9-THC that are ineffective alone suppresses cisplatin-induced emetic reactions in shrews.

Attitudes, management and consequences of nausea and vomiting of pregnancy in the United States and Canada.

PubMed

Mazzotta, P; Maltepe, C; Navioz, Y; Magee, L A; Koren, G

2000-09-01

Nausea and vomiting of pregnancy (NVP) affects a large proportion of pregnant women. In 1983, Bendectin((R)), the only FDA-approved drug for NVP, was removed from the market by its manufacturer due to legal costs based on claims of teratogenicity, which were subsequently proven to be unsubstantiated. In Canada, a generic form of Bendectin (Diclectin; a doxylamine/pyridoxine combination) has continued to be available, with increasing use over the last few years. To characterize the attitudes, management and consequences of NVP among pregnant women in the USA, where no approved drug for NVP is available, and in Canada, where such a drug is available. Prospective, observational study. Women suffering from NVP (N = 1444) were interviewed, of which 42% were American and 58% were Canadian. The two groups had similar maternal characteristics and a similar distribution of severity of NVP, although among Canadian women the NVP continued for slightly longer. American respondents were treated significantly more often by an obstetrician as their primary caregiver, were more commonly advised by their caregiver to change their diet and/or lifestyle and to use non-pharmacological agents to manage their NVP, and more often perceived anti-emetics as posing an increased risk for malformations (all P < 0.001). Canadian respondents reported a family physician as their primary caregiver significantly more often, were more commonly advised to take anti-emetic medications and perceived their NVP as causing a concern to their unborn (all P < 0.001). American women experienced significantly larger weight loss, more hospitalizations and more time lost from paid work. Lack of an approved drug for symptoms of NVP may be associated with unwarranted and preventable adverse health effects. Because this is an observational study, these associations do not necessarily prove causation.

Chewing gum for the treatment of postoperative nausea and vomiting: a pilot randomized controlled trial.

PubMed

Darvall, J N; Handscombe, M; Leslie, K

2017-01-01

A novel treatment, chewing gum, may be non-inferior to ondansetron in inhibiting postoperative nausea and vomiting (PONV) in female patients after laparoscopic or breast surgery. In this pilot study, we tested the feasibility of a large randomized controlled trial. We randomized 94 female patients undergoing laparoscopic or breast surgery to ondansetron 4 mg i.v. or chewing gum if PONV was experienced in the postanaesthesia care unit (PACU). The primary outcome was full resolution of PONV, with non-inferiority defined as a difference between groups of <15% in a per protocol analysis. Secondary outcomes were PACU stay duration, anti-emetic rescue use, and acceptability of anti-emetic treatment. The feasibility of implementing the protocol in a larger trial was assessed. Postoperative nausea and vomiting in the PACU occurred in 13 (28%) ondansetron patients and 15 (31%) chewing gum patients (P=0.75). Three chewing gum patients could not chew gum when they developed PONV. On a per protocol basis, full resolution of PONV occurred in five of 13 (39%) ondansetron vs nine of 12 (75%) chewing gum patients [risk difference 37% (6.3-67%), P=0.07]. There was no difference in secondary outcomes between groups. Recruitment was satisfactory, the protocol was acceptable to anaesthetists and nurses, and data collection was complete. In this pilot trial, chewing gum was not inferior to ondansetron for treatment of PONV after general anaesthesia for laparoscopic or breast surgery in female patients. Our findings demonstrate the feasibility of a larger, multicentred randomized controlled trial to investigate this novel therapy. Australian New Zealand Clinical Trials Registry: ACTRN12615001327572. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of zacopride and BMY25801 (batanopride) on radiation-induced emesis and locomotor behavior in the ferret

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, G.L.; Landauer, M.R.

1990-06-01

The antiemetic and locomotor effects of two substituted benzamides, zacopride and batanopride (BMY25801), were compared in ferrets after bilateral 60Co irradiation at 2, 4 or 6 Gy. Both zacopride and BMY25801 were effective against emesis and related signs. Zacopride, tested at several doses (0.003, 0.03 and 0.3 mg/kg), appeared to be more potent because it abolished emesis at 100-fold lower doses than did BMY25801 (3 mg/kg). The ED50 value for the antiemetic effect of zacopride was 0.026 mg/kg (confidence levels = 0.0095, 0.072 mg/kg). However, analysis of emetic parameters recorded from vomiting animals (e.g., latency to first emesis) demonstrated thatmore » BMY25801 provided greater antiemetic protection in this population than zacopride without any apparent side effects. Locomotor activity was significantly depressed by both radiation (all doses) and zacopride alone (0.03 mg/kg and 0.3 mg/kg). BMY25801 alone did not affect locomotor activity, and protected against the radiation-induced locomotor decrement. Although zacopride potentiated the locomotor decrement to radiation, no clear dose-response relationship was evident. Bilateral abdominal vagotomy significantly increased the latency to the first emetic episode and significantly reduced the number of retches, but did not alter the duration of the prodromal response to 4-Gy irradiation. Unilateral vagotomies had no effect. Zacopride (at 0.03 mg/kg and 0.3 mg/kg) remained an effective antiemetic in animals that received a bilateral vagotomy, abolishing emesis in four of eight and two of eight ferrets, respectively. These data suggest that the antiemetic action of zacopride does not fully depend on intact vagal innervation and also acts via other pathways.« less

Systematic review on the recurrence of postoperative nausea and vomiting after a first episode in the recovery room – implications for the treatment of PONV and related clinical trials

PubMed Central

Eberhart, Leopold HJ; Frank, Silke; Lange, Henning; Morin, Astrid M; Scherag, André; Wulf, Hinnerk; Kranke, Peter

2006-01-01

Background Despite the presence of a plethora of publications on the prevention of postoperative nausea and vomiting (PONV) only little is known how to treat established symptoms. Besides the high effort of performing these efficacy trials (much more patients must give their consent than are actually included in a study) and ethical concerns, little is known about the rate of re-occurring PONV/vomiting after placebo. As a consequence investigators will have difficulties defining a clinically relevant effect for the new treatment which is crucial for any planning. A quantitative systematic review was performed in order to provide more reliable estimates of the incidence of re-occurring PONV/vomiting after placebo and to help investigators defining a clinically relevant treatment effect. Methods A systematic search of the literature was performed using an extended search strategy of a previous review. Data on the recurrence of PONV (any nausea or emetic symptom) and vomiting (retching or vomiting) was extracted from published reports treating PONV with placebo and unpublished results from two observational trials where no treatment was given. A nonlinear random effects model was used to calculate estimates of the recurrence of symptoms and their 95%-confidence intervals (95%-CI). Results A total of 29 trials (including the unpublished data) were eligible for the calculations. Depending on the length of observation after administering placebo or no treatment the recurrence rate of PONV was between 65% (95%-CI: 53%...75%) and 84% (95%-CI: 73%...91%) and that of vomiting was between 65% (95%-CI: 44%...81%) and 78% (95%-CI: 59%...90%). Conclusion Almost all trials showed a considerable and consistently high rate of recurrence of emetic symptoms after placebo highlighting the need for a consequent antiemetic treatment. Future (placebo) controlled efficacy trials may use the presented empirical estimates for defining clinically relevant effects and for statistical power

Adjuvant and induction chemotherapy in non-small cell lung cancer.

PubMed

Pirker, R; Malayeri, R; Huber, H

1999-01-01

About 25%-30% of patients with non-small cell lung cancer can be resected with curative intent. However, systemic relapses occur in up to 70% of these patients. Thus, postoperative adjuvant chemotherapy was evaluated in several randomised trials but the results of these trials were inconclusive with a survival benefit only in some trials. Shortcomings of these trials included low number of patients, poor patient compliance and inadequate chemotherapy protocols. A recent meta-analysis suggested an absolute survival benefit of 5% at five years for postoperative cisplatin-based chemotherapy as compared to surgery alone. Thus adjuvant chemotherapy with both improved chemotherapy protocols and improved anti-emetics is currently re-evaluated in several randomised trials on large patient populations.

Blockade of 5-hydroxytryptamine(3) receptors prevents cisplatin-induced but not motion- or xylazine-induced emesis in the cat

NASA Technical Reports Server (NTRS)

Lucot, James B.

1989-01-01

The effects of the 5-hydroxytryptamine(3) (5-HT-3) antagonists ICS 205-930 and MDL 72222 on the emesis induced by motion or by emetic doses of xylazine (0.66 mg/kg administered SC) or cisplatin (7.5 mg/kg infused over a period of 4-5 min) were investigated in cats. It was found that neither the low (0.1 mg/kg) or the high (1.0 mg.kg) doses of ICS 205-930 or MDL 72222 prevented emesis elicited by screening motion challenges or xylazine. On the other hand, treatment cats by 1.0 mg/kg of ICS 205-930 was effective against cisplatin-induced motion sickness, in agreement with earlier results obtained on other mammals.

Drug inhibition of first-stage radioemesis. Interim report, 5 November 1975--31 December 1976

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gralla, E.J.; Krupp, J.H.; Mattsson, J.L.

1977-06-01

An animal model of irradiation-induced emesis was developed which involved exposing young male beagle dogs to 800 rads in the abdominal area. This caused a 100% incidence of emesis within 8 hr and a second wave of emesis and hemorrhagic diarrhea approximately 48 hr later. Seven drugs and one combination of two drugs were examined for effects against these responses. Chlorpromazine proved to be the most potent antagonist of first-stage emesis while dimenhydrinate and diphenhydramine HC1 showed the same activity but to a lesser degree. Inactive drugs were phenytoin sodium, perphenazine (at a low dose), WR2721, and the combination ofmore » amphetamine plus scopolamine. Acetylsalicylic acid intensified the emetic responses. (Author)« less

The Neurobiological Mechanism of Chemical Aversion (Emetic) Therapy for Alcohol Use Disorder: An fMRI Study

PubMed Central

Elkins, Ralph L.; Richards, Todd L.; Nielsen, Robert; Repass, Richard; Stahlbrandt, Henriettae; Hoffman, Hunter G.

2017-01-01

A recent NIH epidemiology study found the lifetime prevalence of alcohol use disorder in the United States to be 29%. Alcohol drinking behavior is strongly “learned” via pleasure center activation/reinforcement. Alcohol craving is a powerful desire to drink alcoholic beverages. Craving was added as one of the defining criteria for alcohol use disorder in DSM5, and craving reduction is becoming an increasingly important treatment goal. In the current study, patients with alcohol use disorder received 10 days of inpatient multi-modal treatments at Schick Shadel Hospital (SSH) of Seattle. The treatments included five chemical aversion conditioning sessions that associated alcohol cues (and alcohol) with nausea and emesis. All patients met DSM4 criteria for alcohol use disorder, were heavy drinkers, and reported craving alcohol pre-treatment. Craving reduction was one of the primary treatment goals. This is the first fMRI study to measure the effects of chemical aversion therapy on alcohol craving-related brain activity. Patients were recruited as subjects for the University of Washington (UW) brain scan study following SSH admission but before treatment onset. Prior to treatment, patients reported craving/desire for alcohol. After treatment (after four SSH chemical aversion treatments, again after five SSH chemical treatments, 30 and 90-days post-discharge), these same patients reported avoidance/aversion to alcohol. Most of the participants (69%) reported being still sober 12 months post-treatment. Consistent with a craving reduction mechanism of how chemical aversion therapy facilitates sobriety, results of the UW fMRI brain scans showed significant pre- to post-treatment reductions in craving-related brain activity in the occipital cortex. Additional fMRI brain scan studies are needed to further explore the neurobiological mechanism of chemical aversion therapy treatment for alcohol use disorder, and other substance use disorders for which chemical aversion therapy is used (e.g., opioid dependence and cocaine dependence). Substance use disorders are estimated to affect well over one billion people worldwide. PMID:29033802

Comparison of pain-relieving effects of fentanyl versus ketorolac after eye amputation surgery.

PubMed

Kim, Jin Hyung; Jang, Sun Young; Kim, Myung Jin; Lee, Sang Yeul; Yoon, Jin Sook

2013-08-01

To investigate the analgesic effect and incidence of postoperative nausea and vomiting (PONV) between the opioid fentanyl and the non-steroidal anti-inflammatory drug ketorolac in patients who underwent eye amputation surgery. Retrospective observational case series. Eighty-two patients underwent evisceration or enucleation surgery by one surgeon over a 2-year period. Fentanyl by intravenous patient-controlled analgesia (IV-PCA) at 20 µg/kg with 12 mg/kg ondansetron or intravenous ketorolac at 2 mg/kg/day was administered to patients at postoperative days 0, 1, and 2. The pain score was measured using an 11-point visual analog scale (VAS). The incidence of severe nausea requiring anti-emetics and the incidence of vomiting were reviewed. The mean postoperative VAS in the fentanyl group was significantly lower than that in the ketorolac group on the day of operation for both types of surgery (p = 0.001 and p = 0.004, respectively). At postoperative days 1 and 2, the mean VAS was not different between the two groups for either surgical type (p > 0.05 for both days). The mean VAS was significantly higher in eviscerated patients than in enucleated patients at postoperative days 0 and 1 in the fentanyl group (p = 0.023 and p = 0.016, respectively). However, this was not observed in the ketorolac group. The incidence of PONV was higher in the fentanyl group than in the ketorolac group, although this was not statistically significant for either surgical type (p > 0.05 for both groups). Fentanyl was more effective as an analgesic than was ketorolac on the day of operation for both surgical types. There was no difference between the two analgesics on postoperative day 1. The analgesic effect of fentanyl in enucleated patients was significantly higher than in eviscerated patients at postoperative days 0 and 1. The use of fentanyl by IV-PCA was associated with greater PONV despite co-administration with anti-emetics, although this finding was not significant.

Comparison of Pain-relieving Effects of Fentanyl versus Ketorolac after Eye Amputation Surgery

PubMed Central

Kim, Jin Hyung; Jang, Sun Young; Kim, Myung Jin; Lee, Sang Yeul

2013-01-01

Purpose To investigate the analgesic effect and incidence of postoperative nausea and vomiting (PONV) between the opioid fentanyl and the non-steroidal anti-inflammatory drug ketorolac in patients who underwent eye amputation surgery. Methods Retrospective observational case series. Eighty-two patients underwent evisceration or enucleation surgery by one surgeon over a 2-year period. Fentanyl by intravenous patient-controlled analgesia (IV-PCA) at 20 µg/kg with 12 mg/kg ondansetron or intravenous ketorolac at 2 mg/kg/day was administered to patients at postoperative days 0, 1, and 2. The pain score was measured using an 11-point visual analog scale (VAS). The incidence of severe nausea requiring anti-emetics and the incidence of vomiting were reviewed. Results The mean postoperative VAS in the fentanyl group was significantly lower than that in the ketorolac group on the day of operation for both types of surgery (p = 0.001 and p = 0.004, respectively). At postoperative days 1 and 2, the mean VAS was not different between the two groups for either surgical type (p > 0.05 for both days). The mean VAS was significantly higher in eviscerated patients than in enucleated patients at postoperative days 0 and 1 in the fentanyl group (p = 0.023 and p = 0.016, respectively). However, this was not observed in the ketorolac group. The incidence of PONV was higher in the fentanyl group than in the ketorolac group, although this was not statistically significant for either surgical type (p > 0.05 for both groups). Conclusions Fentanyl was more effective as an analgesic than was ketorolac on the day of operation for both surgical types. There was no difference between the two analgesics on postoperative day 1. The analgesic effect of fentanyl in enucleated patients was significantly higher than in eviscerated patients at postoperative days 0 and 1. The use of fentanyl by IV-PCA was associated with greater PONV despite co-administration with anti-emetics, although this finding

Improvement of spatial memory function in APPswe/PS1dE9 mice after chronic inhibition of phosphodiesterase type 4D.

PubMed

Sierksma, A S R; van den Hove, D L A; Pfau, F; Philippens, M; Bruno, O; Fedele, E; Ricciarelli, R; Steinbusch, H W M; Vanmierlo, T; Prickaerts, J

2014-02-01

Phosphodiesterase type 4 inhibitors (PDE4-Is) have received increasing attention as cognition-enhancers and putative treatment strategies for Alzheimer's disease (AD). By preventing cAMP breakdown, PDE4-Is can enhance intracellular signal transduction and increase the phosphorylation of cAMP response element-binding protein (CREB) and transcription of proteins related to synaptic plasticity and associated memory formation. Unfortunately, clinical development of PDE4-Is has been seriously hampered by emetic side effects. The new isoform-specific PDE4D-I, GEBR-7b, has shown to have beneficial effects on memory at non-emetic doses. The aim of the current study was to investigate chronic cognition-enhancing effects of GEBR-7b in a mouse model of AD. To this extent, 5-month-old (5M) APPswe/PS1dE9 mice received daily subcutaneous injections with GEBR-7b (0.001 mg/kg) or vehicle for a period of 3 weeks, and were tested on affective and cognitive behavior at 7M. We demonstrated a cognition-enhancing potential in APPswe/PS1dE9 mice as their spatial memory function at 7M in the object location test was improved by prior GEBR-7b treatment. APPswe/PS1dE9 mice displayed lower levels of CREB phosphorylation, which remained unaltered after chronic GEBR-7b treatment, and higher levels of tau in the hippocampus. Hippocampal brain-derived neurotrophic factor levels and synaptic densities were not different between experimental groups and no effects were observed on hippocampal GSK3β and tau phosphorylation or Aβ levels. In conclusion, GEBR-7b can enhance spatial memory function in the APPswe/PS1dE9 mouse model of AD. Although the underlying mechanisms of its cognition-enhancing potential remain to be elucidated, PDE4D inhibition appears an interesting novel therapeutic option for cognitive deficits in AD. Copyright © 2013 Elsevier Ltd. All rights reserved.

THE PHARMACOLOGY OF RADIOPROTECTANT CHEMICALS. GENERAL PHARMACOLOGY OF / cap beta/-MERCAPTOETHYLAMINE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mundy, R.L.; Heiffer, M.H.

1960-09-01

When 100 mg of beta -mercaptoethylamine is administered intravenously to the dog over a period of 5 min a characteristic set of reactions is produced. The most notable of these in the nonanesthetized dog are violent emesis, agitation frequently leading to tonic-clonic convulsions, ataxia and a characteristic swaying movement of the front portion of the body, generalized depression, loss of pain sense, severe hypotension, relative bradycardia, blood- tinged diarrhea, and a mixed stimulation and depression of respiration. Anesthesia prevents the emetic and convulsive components of the reaction but does not affect the cardiovascular changes. The agent produces a delayed, severe,more » prolonged hypotension. The possibility is discussed that the physiological changes produced by this agent may contribute to its radioprotective potential. 27 references. (auth)« less

Current status: Animal models of nausea

NASA Technical Reports Server (NTRS)

Fox, Robert A.

1991-01-01

The advantages, and possible benefits of a valid, reliable animal model for nausea are discussed, and difficulties inherent to the development of a model are considered. A principle problem for developing models arises because nausea is a subjective sensation that can be identified only in humans. Several putative measures of nausea in animals are considered, with more detailed consideration directed to variation in cardiac rate, levels of vasopressin, and conditioned taste aversion. Demonstration that putative measures are associated with reported nausea in humans is proposed as a requirement for validating measures to be used in animal models. The necessity for a 'real-time' measure of nausea is proposed as an important factor for future research; and the need for improved understanding of the neuroanatomy underlying the emetic syndrome is discussed.

Extracorporeal virus elimination for the treatment of severe Ebola virus disease--first experience with lectin affinity plasmapheresis.

PubMed

Büttner, Stefan; Koch, Benjamin; Dolnik, Olga; Eickmann, Markus; Freiwald, Tilo; Rudolf, Sarah; Engel, Jürgen; Becker, Stephan; Ronco, Claudio; Geiger, Helmut

2014-01-01

Therapeutic options for Ebola virus disease (EVD) are currently limited to (1) best supportive care, and (2) evolving virus-specific therapies, resulting from decades of analyzing one of the world's deadliest diseases. Supportive care ranges from oral or intravenous rehydration therapy and anti-emetics in developing countries to much more extensive life-support interventions in resource-rich countries. Current EVD-specific therapies attempt to either interfere with the earliest steps of viral replication or to elicit a strong immune response against the virus. An entirely new approach is the extracorporeal elimination of viruses and viral glycoproteins by lectin affinity plasmapheresis. Herein, we report for the first time the successful and safe use of lectin affinity plasmapheresis in a patient with severe Ebola virus disease. © 2015 S. Karger AG, Basel.

Emesis in dogs: a review.

PubMed

Elwood, C; Devauchelle, P; Elliott, J; Freiche, V; German, A J; Gualtieri, M; Hall, E; den Hertog, E; Neiger, R; Peeters, D; Roura, X; Savary-Bataille, K

2010-01-01

Emesis is a common presenting sign in small animal practice. It requires a rational approach to management that is based upon a sound understanding of pathophysiology combined with logical decision making. This review, which assesses the weight of available evidence, outlines the physiology of the vomiting reflex, causes of emesis, the consequences of emesis and the approach to clinical management of the vomiting dog. The applicability of diagnostic testing modalities and the merit of traditional approaches to management, such as dietary changes, are discussed. The role and usefulness of both traditional and novel anti-emetic drugs is examined, including in specific circumstances such as following cytotoxic drug treatment. The review also examines areas in which common clinical practice is not necessarily supported by objective evidence and, as such, highlights questions worthy of further clinical research.

Efficacy of maropitant for preventing vomiting associated with motion sickness in dogs.

PubMed

Benchaoui, H A; Siedek, E M; De La Puente-Redondo, V A; Tilt, N; Rowan, T G; Clemence, R G

2007-09-29

Maropitant is a neurokinin-1 inhibitor that acts to prevent and treat vomiting by blocking stimuli to the final common pathway in the emetic centre of the brain. The field efficacy and safety of a single oral dose of maropitant were investigated for the prevention of vomiting in dogs with a history of motion sickness resulting from transportation by car in two blinded, placebo-controlled studies. In an exploratory study designed as a two-way crossover trial with 17 dogs, 10 of the dogs given the placebo vomited during a car journey but only three of the dogs vomited under maropitant treatment. In a larger multicentred parallel design study, 69 of 105 dogs treated with the placebo vomited during the journey compared with 15 of 106 dogs treated with maropitant (P < 0.0001).

RANDOMNESS of Numbers DEFINITION(QUERY:WHAT? V HOW?) ONLY Via MAXWELL-BOLTZMANN CLASSICAL-Statistics(MBCS) Hot-Plasma VS. Digits-Clumping Log-Law NON-Randomness Inversion ONLY BOSE-EINSTEIN QUANTUM-Statistics(BEQS) .

NASA Astrophysics Data System (ADS)

Siegel, Z.; Siegel, Edward Carl-Ludwig

2011-03-01

RANDOMNESS of Numbers cognitive-semantics DEFINITION VIA Cognition QUERY: WHAT???, NOT HOW?) VS. computer-``science" mindLESS number-crunching (Harrel-Sipser-...) algorithmics Goldreich "PSEUDO-randomness"[Not.AMS(02)] mea-culpa is ONLY via MAXWELL-BOLTZMANN CLASSICAL-STATISTICS(NOT FDQS!!!) "hot-plasma" REPULSION VERSUS Newcomb(1881)-Weyl(1914;1916)-Benford(1938) "NeWBe" logarithmic-law digit-CLUMPING/ CLUSTERING NON-Randomness simple Siegel[AMS Joint.Mtg.(02)-Abs. # 973-60-124] algebraic-inversion to THE QUANTUM and ONLY BEQS preferentially SEQUENTIALLY lower-DIGITS CLUMPING/CLUSTERING with d = 0 BEC, is ONLY VIA Siegel-Baez FUZZYICS=CATEGORYICS (SON OF TRIZ)/"Category-Semantics"(C-S), latter intersection/union of Lawvere(1964)-Siegel(1964)] category-theory (matrix: MORPHISMS V FUNCTORS) "+" cognitive-semantics'' (matrix: ANTONYMS V SYNONYMS) yields Siegel-Baez FUZZYICS=CATEGORYICS/C-S tabular list-format matrix truth-table analytics: MBCS RANDOMNESS TRUTH/EMET!!!

A review of chemistry and biological activities of the genus Aerva--a desert plant.

PubMed

Chawla, Payal; Chawla, Amit; Vasudeva, Neeru; Sharma, Surendra Kumar

2012-01-01

There are approximately 28 species of Aerva genus, but only a few species are medicinal of which A. persica, A. lanata and A. javanica are of great value. A number of flavonol glycosides (e.g., aervanone, kaempferol-3-galactoside, isorhamnetin-3-O-β-D-glucoside) have been reported from Aerva persica as major phytoconstituents and the minor constituents are β-cyanins (glycine betaine and trigonelline), sterols and carbohydrates. This plant is used as medicinal herb in several traditional systems of medicine all over the world, like diuretic, demulcent, purgative, emetic and tinder. Aerva plants are used to cure ulcer, lithiasis, dropsical affections, eye affection, toothache, headache, in disorders of abdomen and inflammation of internal organs. Roots and flowers are reported to possess hypoglycemic, antioxidant, anthelmintic, analgesic, antimalarial, antivenin activities and medicinal properties against rheumatism and kidney troubles.

Inhibition of radioemesis by disruption of catecholamines in dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luthra, Y.K.; Mattsson, J.L.; Yochmowitz, M.G.

1981-03-01

Dogs were treated 30 min to 1 h before x irradiation with ..cap alpha..-methyl-p-tyrosine or 6-hydroxydopamine. A third group of dogs was given a known antiradioemetic drug, haloperidol to verify the sensitivity of the procedure. Irradiated but untreated controls were also used. Light methoxyflurane anesthesia was used for restraint during the exposure. Exposure dose was 800 rad kerma delivered at 50 rad/min to a 10 x 10-cm area covering the abdominal area from xiphoid to pubis. Haloperidol and 6-hydroxydopamine significantly reduced the number of emetic episodes and delayed the onset time to the first episode, ..cap alpha..-Methyl-p-tyrosine caused no significantmore » changes. The effectiveness of 6-hydroxydopamine indicates that catecholaminergic neurons are involved in radioemesis, whereas haloperidol and phenothiazine-derivative tranquilizers inhibit radiomesis by blocking catecholamine receptor neurons.« less

Effects of oral 3% hydrogen peroxide used as an emetic on the gastroduodenal mucosa of healthy dogs.

PubMed

Niedzwecki, Alicia H; Book, Bradley P; Lewis, Kristin M; Estep, J Scot; Hagan, Joseph

2017-03-01

To characterize the extent of mucosal injury on the upper gastrointestinal tract following oral administration of 3% hydrogen peroxide (H 2 O 2 ) to induce emesis in normal dogs. Prospective clinical study. Specialty referral hospital. Seven staff-owned, healthy, adult dogs. Six dogs were assigned to the H 2 O 2 group and 1 dog was assigned as the apomorphine control. Dogs were anesthetized for gastroduodenoscopy with gross inspection and gastroduodenal biopsies at time 0 and 4 hours, 24 hours, 1 week, and 2 weeks following administration of oral 3% H 2 O 2 or subconjunctival apomorphine. Gross esophageal, gastric, and duodenal mucosal lesion scoring was performed by 2 blinded, experienced scorers. Biopsy samples were evaluated histologically by a veterinary pathologist. Grade I esophagitis was noted in 2 dogs at 4 hours and in 1 dog at 2 weeks, while grade III esophagitis was observed in 1 dog 1 week following H 2 O 2 administration. At 4 hours, gastric mucosal lesions were visualized in all dogs, and lesions worsened by 24 hours. Mild to moderate duodenal mucosal lesions were visualized up to 24 hours after administration. Histopathology identified the most severe gastric lesions at 4 hours as hemorrhage; at 24 hours as degeneration, necrosis, and mucosal edema; and at 1 week as inflammation. By 2 weeks, most visual and histopathologic lesions were resolved. No histopathologic lesions were identified at any time point in the dog administered apomorphine. Significant visual and histopathologic gastric lesions occurred following administration of 3% H 2 O 2 in all dogs. Less severe visual duodenal lesions were identified. As compared to H 2 O 2 dogs, minimal gross gastroduodenal lesions and normal histopathology were identified in the apomorphine control. © Veterinary Emergency and Critical Care Society 2016.

Anti-emetic mechanisms of Zingiber officinale against cisplatin induced emesis in the pigeon; behavioral and neurochemical correlates.

PubMed

Ullah, Ihsan; Subhan, Fazal; Ayaz, Muhammad; Shah, Rehmat; Ali, Gowhar; Haq, Ikram Ul; Ullah, Sami

2015-02-26

Zingiber officinale (ZO, family Zingiberaceae) has been reported for its antiemetic activity against cancer chemotherapy induced emesis in animal models and in clinics. Current study was designed to investigate ZO for potential usefulness against cisplatin induced vomiting in pigeon and its effects on central and peripheral neurotransmitters involved in the act of vomiting. Zingiber officinale acetone fraction (ZO-ActFr) was investigated for attenuation of emesis induced by cisplatin in healthy pigeons. Neurotransmitters DA, 5HT and their metabolites DOPAC, HVA and 5HIAA were analyzed using High Performance Liquid Chromatography system coupled with electrochemical detector in area postrema, brain stem and intestine. Antiemetic effect of ZO-ActFr was correlated with central and intestinal neurotransmitters levels in pigeon. Cisplatin (7 mg/kg i.v.) induced emesis without lethality upto the observation period. ZO-ActFr (25, 50 & 100 mg/kg) attenuated cisplatin induced emesis ~ 44.18%, 58.13% (P < 0.05) and 27.9%, respectively; the reference drug, metoclopramide (MCP; 30 mg/kg), produced ~ 48.83% reduction (P < 0.05). ZO-ActFr reduced (P < 0.05 - 0.001) 5-hydroxytryptamine (5HT) concentration in the area postrema, brain stem and intestine at 3(rd) hour of cisplatin administration, while at the 18(th) hour ZO treatments attenuated the dopamine upsurge (P < 0.001) caused by cisplatin in the area postrema and 5HT concentration (P < 0.01 - 0.001) in the brain stem and intestine. ZO treatments alone did not altered the basal neurotransmitters and their metabolites in the brain areas and intestine. The behavioral study verify the antiemetic profile of ZO against cisplatin induced emesis in the pigeon, where central and peripheral neural evidences advocate the involvement of serotonergic mechanism at initial time point (3(rd) hr), while the later time point (18(th) hr) is associated with serotonergic and dopaminergic component in the mediation of its antiemetic effect.

Relationship of area postrema to three putative measures of motion sickness

NASA Technical Reports Server (NTRS)

Sutton, R.; Fox, Robert A.; Daunton, Nancy G.

1991-01-01

Although the rat has an incomplete emetic reflex, several species-specific responses to motion were proposed as measures of 'motion sickness' in rats. The purpose was to determine the dependence of these responses on one of several neural structures known to be essential to motion-induced vomiting in species with a complete emetic reflex. The Area Postrema (AP) was shown to play an important role in the production of motion sickness in vomiting species. The effects of thermo-cautery ablations of the AP on three different responses supposedly reflecting motion sickness in the rat were compared: conditioned taste aversion (CTA); drinking suppression; and fecal boli. Efficacy of the ablations was determined by subjecting ablated, sham-operated, and unoperated control animals to a CTA test which is known to require a functional AP. Animals with AP ablations failed to form CTA when 0.15 M LiCl was paired with a 10 percent sucrose solution, while sham-operated control subjects conditioned as well as the unoperated control subjects. The extent of the ablations was evaluated histologically at the end of the experiment. To determine the effects of the ablations on the measures of motion sickness, all animals were subjected to rotation for 30 min or 90 min on a platform displaced 20 deg from earth horizontal. Results indicate that ablation of AP in the rat has no effect on the formation of CTA to a 4 percent solution of cider paired with motion, on the suppression of drinking immediately after exposure to motion, or on the frequency of fecal boli during exposure to motion. This failure of AP ablations to eliminate the effects of motion on any of these responses discourages their use as equivalents of motion-induced vomiting. The appropriateness of other suggested measures, e.g., pica, remains untested but the dependence of such measures on stimulation more severe than commonly used in motion sickness research and the absence of a demonstration of their dependence on neural

The Endospore-Forming Pathogen Bacillus cereus Exploits a Small Colony Variant-Based Diversification Strategy in Response to Aminoglycoside Exposure.

PubMed

Frenzel, Elrike; Kranzler, Markus; Stark, Timo D; Hofmann, Thomas; Ehling-Schulz, Monika

2015-12-08

Bacillus cereus is among the microorganisms most often isolated from cases of food spoilage and causes gastrointestinal diseases as well as nongastrointestinal infections elicited by the emetic toxin cereulide, enterotoxins, and a panel of tissue-destructive virulence factors. This opportunistic pathogen is increasingly associated with rapidly fatal clinical infections especially linked to neonates and immunocompromised individuals. Fatality results from either the misdiagnosis of B. cereus as a contaminant of the clinical specimen or from failure of antibiotic therapy. Here we report for the first time that exposure to aminoglycoside antibiotics induces a phenotype switching of emetic B. cereus subpopulations to a slow-growing small colony variant (SCV) state. Along with altered antibiotic resistance, SCVs showed distinct phenotypic and metabolic properties, bearing the risk of antibiotic treatment failure and of clinical misdiagnosis by standard identification tests used in routine diagnostic. The SCV subpopulation is characterized by enhanced production of the toxin cereulide, but it does not secrete tissue-destructive and immune system-affecting enzymes such as sphingomyelinase and phospholipase. SCVs showed significantly prolonged persistence and decreased virulence in the Galleria mellonella model for bacterial infections, indicating diversification concerning their ecological lifestyle. Importantly, diversification into coexisting wild-type and SCV subpopulations also emerged during amikacin pressure during in vivo infection experiments. This study shows for the first time that pathogenic spore-forming B. cereus strains are able to switch to a so far unreported slow-growing lifestyle, which differs substantially in terms of developmental, phenotypic, metabolic, and virulence traits from the wild-type populations. This underpins the necessity of molecular-based differential diagnostics and a well-chosen therapeutic treatment strategy in clinical

Determination of Soil Erosion Risk in the Mustafakemalpasa River Basin, Turkey, Using the Revised Universal Soil Loss Equation, Geographic Information System, and Remote Sensing

NASA Astrophysics Data System (ADS)

Ozsoy, Gokhan; Aksoy, Ertugrul; Dirim, M. Sabri; Tumsavas, Zeynal

2012-10-01

Sediment transport from steep slopes and agricultural lands into the Uluabat Lake (a RAMSAR site) by the Mustafakemalpasa (MKP) River is a serious problem within the river basin. Predictive erosion models are useful tools for evaluating soil erosion and establishing soil erosion management plans. The Revised Universal Soil Loss Equation (RUSLE) function is a commonly used erosion model for this purpose in Turkey and the rest of the world. This research integrates the RUSLE within a geographic information system environment to investigate the spatial distribution of annual soil loss potential in the MKP River Basin. The rainfall erosivity factor was developed from local annual precipitation data using a modified Fournier index: The topographic factor was developed from a digital elevation model; the K factor was determined from a combination of the soil map and the geological map; and the land cover factor was generated from Landsat-7 Enhanced Thematic Mapper (ETM) images. According to the model, the total soil loss potential of the MKP River Basin from erosion by water was 11,296,063 Mg year-1 with an average soil loss of 11.2 Mg year-1. The RUSLE produces only local erosion values and cannot be used to estimate the sediment yield for a watershed. To estimate the sediment yield, sediment-delivery ratio equations were used and compared with the sediment-monitoring reports of the Dolluk stream gauging station on the MKP River, which collected data for >41 years (1964-2005). This station observes the overall efficiency of the sediment yield coming from the Orhaneli and Emet Rivers. The measured sediment in the Emet and Orhaneli sub-basins is 1,082,010 Mg year-1 and was estimated to be 1,640,947 Mg year-1 for the same two sub-basins. The measured sediment yield of the gauge station is 127.6 Mg km-2 year-1 but was estimated to be 170.2 Mg km-2 year-1. The close match between the sediment amounts estimated using the RUSLE-geographic information system (GIS) combination

Antiemetic efficacy of smoked marijuana: subjective and behavioral effects on nausea induced by syrup of ipecac.

PubMed

Söderpalm, A H; Schuster, A; de Wit, H

2001-01-01

Although the public debate about the legalization of marijuana has continued for as long as 25 years, few controlled studies have been conducted to assess its potential medical benefits. The present study examined the antiemetic effect of smoked marijuana cigarettes (8.4 and 16.9 mg Delta(9)-tetrahydrocannabinol [THC]) compared to a highly potent antiemetic drug, ondansetron (8 mg) in 13 healthy volunteers. Nausea and emesis were induced by syrup of ipecac. Marijuana significantly reduced ratings of "queasiness" and slightly reduced the incidence of vomiting compared to placebo. Ondansetron completely eliminated the emetic effects of ipecac. These findings support and extend previous results, indicating that smoked marijuana reduces feelings of nausea and also reduces emesis in this model. However, its effects are very modest relative to ondansetron, and the psychoactive effects of marijuana are likely to limit its clinical usefulness in the general population.

Dental treatment in patients with severe gag reflex using propofol-remifentanil intravenous sedation

PubMed Central

Shin, Sooil

2017-01-01

Patients with severe gag reflex (SGR) have difficulty getting the treatment they require in local clinics, and many tend to postpone the start of their treatment. To address this problem, dentists have used behavioral techniques and/or pharmacological techniques for treatment. Among the pharmacological methods available, propofol IV sedation is preferred over general anesthesia because it is a simpler procedure. Propofol in combination with remifentanil is characterized by stable sedative effects and quick recovery, leading to a deep sedation. Remifentanil acts to reduce the pain caused by lipid-soluble propofol on injection. The synergistic effects of propofol-remifentanil include reduction in the total amount of drug required to achieve a desired sedation level and anti-emetic effects. In this case report, we outline how the use of propofol-remifentanil IV sedation enabled us to successfully complete a wide range of dental treatments in a patient with SGR. PMID:28879331

Dental treatment in patients with severe gag reflex using propofol-remifentanil intravenous sedation.

PubMed

Shin, Sooil; Kim, Seungoh

2017-03-01

Patients with severe gag reflex (SGR) have difficulty getting the treatment they require in local clinics, and many tend to postpone the start of their treatment. To address this problem, dentists have used behavioral techniques and/or pharmacological techniques for treatment. Among the pharmacological methods available, propofol IV sedation is preferred over general anesthesia because it is a simpler procedure. Propofol in combination with remifentanil is characterized by stable sedative effects and quick recovery, leading to a deep sedation. Remifentanil acts to reduce the pain caused by lipid-soluble propofol on injection. The synergistic effects of propofol-remifentanil include reduction in the total amount of drug required to achieve a desired sedation level and anti-emetic effects. In this case report, we outline how the use of propofol-remifentanil IV sedation enabled us to successfully complete a wide range of dental treatments in a patient with SGR.

Chemotherapeutic reactions of Chandlerella hawkingi, the filarial parasite of the Indian jungle crow, Corvus macrorhynchos (Wagler)

PubMed Central

Chatterjee, R. K.; Sen, A. B.

1969-01-01

1. A high percentage of Indian jungle crows (Corvus macrorhynchos Wagler), found in and around Lucknow, harbour a natural filarial infection Chandlerella hawkingi. The microfilariae of this species are sheathed and show nocturnal periodicity. 2. Fourteen compounds active against other kinds of filariae, especially against Litomosoides carinii, were tested against Ch. hawkingi in jungle crows to find whether this infection would be suitable for routine filarial chemotherapy. This is apparently the first report of systematic screening of antifilarial compounds against an avian filariasis. 3. Tartar emetic (10 mg/kg intravenously, daily for 6 days) and arsenamide (5 mg/kg intraperitoneally, daily for 6 days) proved to be effective in killing adult worms. Trivalent tryparsamide, though effective, was toxic in the doses tried. Diethylcarbamazine and other compounds tested were ineffective. 4. The chemotherapeutic susceptibilities of Ch. hawkingi differ considerably from those of L. carinii and Wuchereria bancrofti. PMID:5774047

Positioning of nasobiliary tube using magnet-loaded catheters.

PubMed

Watanabe, Seitaro; Sato, Takamitsu; Kato, Shingo; Hosono, Kunihiro; Kobayashi, Noritoshi; Nakajima, Atsushi; Kubota, Kensuke

2013-10-01

In endoscopic nasobiliary drainage (ENBD), repositioning the catheter from the mouth to the nose is complicated. We devised a method using catheters with magnets and verified its utility and safety. We prospectively enrolled 20 patients undergoing ENBD at Yokohama City University Hospital. The procedures were successful in all 20 cases and no case required a change of operators to a senior doctor. The mean time for the procedure was 36.6 seconds. The emetic reflex was induced 0.5 times on average using the magnet method. The mean X-ray exposure time was 29.6 seconds. No complications occurred. The magnet-loaded catheter method for positioning the ENBD catheter before finally leading it through the nose took little time and was performed successfully and safely. Therefore, the magnet method could become the first choice among techniques for ENBD catheter placement. © Georg Thieme Verlag KG Stuttgart · New York.

Low-dose metronomic, multidrug therapy with the PEP-C oral combination chemotherapy regimen for mantle cell lymphoma.

PubMed

Coleman, Morton; Martin, Peter; Ruan, Jia; Furman, Richard; Niesvizky, Ruben; Elstrom, Rebecca; George, Patricia; Leonard, John; Kaufmann, Thomas

2008-03-01

The prednisone, etoposide, procarbazine and cyclophosphamide (PEP-C) oral combination chemotherapy regimen (prednisone 20 mg, cyclophosphamide 50 mg, etoposide 50 mg, and procarbazine 50 mg with an oral anti-emetic) was employed at our center to treat 22 patients with heavily pretreated, recurrent mantle cell lymphoma (MCL). All medications were administered daily until leukocytes fell to <3.0 x 10(9)/L whereupon treatment was withheld until recovery from the nadir. Therapy was then reinstituted on a daily, alternate day, or fractionated basis (e.g. 5 of 7 days) depending on patient tolerance. Doses given per day were held constant. Eighty-two percent achieved an objective response with 46% complete responses and 36% partial responses. Median time on therapy was 17 months. The regimen was well tolerated. Our findings demonstrate that low-dose oral agents administered in combination for continuous, prolonged periods with minimal drug-free intervals (metronomic therapy) may represent a novel, effective, easily tolerated approach to MCL and that this treatment approach warrants further exploration.

Modelisation des emissions de particules microniques et nanometriques en usinage

NASA Astrophysics Data System (ADS)

Khettabi, Riad

La mise en forme des pieces par usinage emet des particules, de tailles microscopiques et nanometriques, qui peuvent etre dangereuses pour la sante. Le but de ce travail est d'etudier les emissions de ces particules pour fins de prevention et reduction a la source. L'approche retenue est experimentale et theorique, aux deux echelles microscopique et macroscopique. Le travail commence par des essais permettant de determiner les influences du materiau, de l'outil et des parametres d'usinage sur les emissions de particules. E nsuite un nouveau parametre caracterisant les emissions, nomme Dust unit , est developpe et un modele predictif est propose. Ce modele est base sur une nouvelle theorie hybride qui integre les approches energetiques, tribologiques et deformation plastique, et inclut la geometrie de l'outil, les proprietes du materiau, les conditions de coupe et la segmentation des copeaux. Il ete valide au tournage sur quatre materiaux: A16061-T6, AISI1018, AISI4140 et fonte grise.

Molecular Bases of PDE4D Inhibition by Memory-Enhancing GEBR Library Compounds.

PubMed

Prosdocimi, Tommaso; Mollica, Luca; Donini, Stefano; Semrau, Marta S; Lucarelli, Anna Paola; Aiolfi, Egidio; Cavalli, Andrea; Storici, Paola; Alfei, Silvana; Brullo, Chiara; Bruno, Olga; Parisini, Emilio

2018-05-01

Selected members of the large rolipram-related GEBR family of type 4 phosphodiesterase (PDE4) inhibitors have been shown to facilitate long-term potentiation and to improve memory functions without causing emetic-like behavior in rodents. Despite their micromolar-range binding affinities and their promising pharmacological and toxicological profiles, few if any structure-activity relationship studies have been performed to elucidate the molecular bases of their action. Here, we report the crystal structure of a number of GEBR library compounds in complex with the catalytic domain of PDE4D as well as their inhibitory profiles for both the long PDE4D3 isoform and the catalytic domain alone. Furthermore, we assessed the stability of the observed ligand conformations in the context of the intact enzyme using molecular dynamics simulations. The longer and more flexible ligands appear to be capable of forming contacts with the regulatory portion of the enzyme, thus possibly allowing some degree of selectivity between the different PDE4 isoforms.

[Acute poisoning in patients over 65 years of age].

PubMed

Miranda Arto, P; Ferrer Dufol, A; Ruiz Ruiz, F J; Menao Guillén, S; Civeira Murillo, E

2014-01-01

There are few Spanish studies on acute poisoning in the elderly despite the associated risk factors of this group of patients. Retrospective descriptive study of acute poisonings treated in the Emergency Service of the University Hospital of Zaragoza from 1995 to 2009 on patients 65 years old or older. A total of 762 patients were selected in the study (4.74% of all acute poisonings) with a mean age of 74.16 (SD ± 6) years. Ingestion was the major route of exposure (85%) and alcohol overdose (28,7%) was the most frequent type of poisoning. A trend was also observed showing a lower emetic treatment and gastric lavage and an increase in activated charcoal. Benzodiazepines (14.3%) and toxic household products (11%) with caustic properties were also the main toxics found in the study. Acute poisonings in the elderly required more hospitalizations, have a higher mortality and more autolytic attempts which result in death.

Pica in Rats as a Preclinical Model of Emesis.

PubMed

Davis, T Gregg

2016-10-03

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. Copyright © 2016 John Wiley & Sons, Inc.

Quantitative Prevalence and Toxin Gene Profile of Bacillus cereus from Ready-to-Eat Vegetables in South Korea.

PubMed

Chon, Jung-Whan; Yim, Jin-Hyeok; Kim, Hong-Seok; Kim, Dong-Hyeon; Kim, Hyunsook; Oh, Deog-Hwan; Kim, Soo-Ki; Seo, Kun-Ho

2015-09-01

Ready-to-eat (RTE) foods such as prepared vegetables are becoming an increasingly popular food choice. Since RTE vegetables are not commonly sterilized by heat treatment, contamination with foodborne pathogens such as Bacillus cereus (B. cereus) is a major concern. The objective of this study was to assess the quantitative prevalence and toxin gene profiles of B. cereus strains isolated from RTE vegetables. We found that 70 of the 145 (48%) tested retail vegetable salad and sprout samples were positive for B. cereus. The B. cereus isolates harbored at least one enterotoxin gene. The detection rates of nheABC, hblCDA, cytK, and entFM enterotoxin genes among all isolates were 97.1%, 100%, 81.4%, and 98.6%, respectively. No strain carried the emetic toxin genes. Only 4 strains (5.7%) from the 70 isolates were psychrotrophic and were able to grow at 7°C. All of the psychrotrophic isolates possessed at least 1 enterotoxin gene.

The Analgesic Potential of Cannabinoids

PubMed Central

Elikottil, Jaseena; Gupta, Pankaj; Gupta, Kalpna

2013-01-01

Historically and anecdotally cannabinoids have been used as analgesic agents. In recent years, there has been an escalating interest in developing cannabis-derived medications to treat severe pain. This review provides an overview of the history of cannabis use in medicine, cannabinoid signaling pathways, and current data from preclinical as well as clinical studies on using cannabinoids as potential analgesic agents. Clinical and experimental studies show that cannabis-derived compounds act as anti-emetic, appetite modulating and analgesic agents. However, the efficacy of individual products is variable and dependent upon the route of administration. Since opioids are the only therapy for severe pain, analgesic ability of cannabinoids may provide a much-needed alternative to opioids. Moreover, cannabinoids act synergistically with opioids and act as opioid sparing agents, allowing lower doses and fewer side effects from chronic opioid therapy. Thus, rational use of cannabis based medications deserves serious consideration to alleviate the suffering of patients due to severe pain. PMID:20073408

Antitumor action of temozolomide, ritonavir and aprepitant against human glioma cells.

PubMed

Kast, Richard E; Ramiro, Susana; Lladó, Sandra; Toro, Salvador; Coveñas, Rafael; Muñoz, Miguel

2016-02-01

In the effort to find better treatments for glioblastoma we tested several currently marketed non-chemotherapy drugs for their ability to enhance the standard cytotoxic drug currently used to treat glioblastoma- temozolomide. We tested four antiviral drugs- acyclovir, cidofovir, maraviroc, ritonavir, and an anti-emetic, aprepitant. We found no cytotoxicity of cidofovir and discussed possible reasons for discrepancy from previous findings of others. We also found no cytotoxicity from acyclovir or maraviroc also in contradistinction to predictions. Cytotoxicity to glioma cell line GAMG for temozolomide alone was 14%, aprepitant alone 7%, ritonavir alone 14%, while temozolomide + aprepitant was 19%, temozolomide + ritonavir 34%, ritonavir + aprepitant 64 %, and all three, temozolomide + ritonavir + aprepitant 78%. We conclude that a remarkable synergy exists between aprepitant and ritonavir. Given the long clinical experience with these two well-tolerated drugs in treating non-cancer conditions, and the current median survival of glioblastoma of 2 years, a trial is warranted of adding these two simple drugs to current standard treatment with temozolomide.

RU 24969-induced emesis in the cat - 5-HT1 sites other than 5-HT1A, 5-HT1B or 5-HT1C implicated

NASA Technical Reports Server (NTRS)

Lucot, James B.

1990-01-01

RU 24969 was administered s.c. to cats and found to elicit emesis with a maximally effective dose of 1.0 mg/kg 5-Methoxytryptamine was found to have lower efficacy and to produce a higher incidence of nonspecific effects while trifluoromethylphenylpiperizine (TFMPP) was devoid of emetic effects. The emesis elicited by 1.0 mg/kg of RU 24969 was not altered by pretreatment with phentolamine, haloperidol, yohimbine or (-)-propranolol, indicating that catecholamines played no role in this response. The emesis was prevented by metergoline and methysergide but not by ketanserin, cyproheptadine, mesulergine, ICS 205 930, methiothepin, trimethobenzamide or BMY 7378. An indirect argument is presented that implicates a role for 5-HT1D sites. This conclusion must remain tentative until drugs selective for this site are synthesized and tested. The emesis was also prevented by 8-hydroxy-2-(di-n-propylamine)tetralin (8-OH-DPAT), confirming that this drug has a general antiemetic effect in cats.

Determination of soil erosion risk in the Mustafakemalpasa River Basin, Turkey, using the revised universal soil loss equation, geographic information system, and remote sensing.

PubMed

Ozsoy, Gokhan; Aksoy, Ertugrul; Dirim, M Sabri; Tumsavas, Zeynal

2012-10-01

Sediment transport from steep slopes and agricultural lands into the Uluabat Lake (a RAMSAR site) by the Mustafakemalpasa (MKP) River is a serious problem within the river basin. Predictive erosion models are useful tools for evaluating soil erosion and establishing soil erosion management plans. The Revised Universal Soil Loss Equation (RUSLE) function is a commonly used erosion model for this purpose in Turkey and the rest of the world. This research integrates the RUSLE within a geographic information system environment to investigate the spatial distribution of annual soil loss potential in the MKP River Basin. The rainfall erosivity factor was developed from local annual precipitation data using a modified Fournier index: The topographic factor was developed from a digital elevation model; the K factor was determined from a combination of the soil map and the geological map; and the land cover factor was generated from Landsat-7 Enhanced Thematic Mapper (ETM) images. According to the model, the total soil loss potential of the MKP River Basin from erosion by water was 11,296,063 Mg year(-1) with an average soil loss of 11.2 Mg year(-1). The RUSLE produces only local erosion values and cannot be used to estimate the sediment yield for a watershed. To estimate the sediment yield, sediment-delivery ratio equations were used and compared with the sediment-monitoring reports of the Dolluk stream gauging station on the MKP River, which collected data for >41 years (1964-2005). This station observes the overall efficiency of the sediment yield coming from the Orhaneli and Emet Rivers. The measured sediment in the Emet and Orhaneli sub-basins is 1,082,010 Mg year(-1) and was estimated to be 1,640,947 Mg year(-1) for the same two sub-basins. The measured sediment yield of the gauge station is 127.6 Mg km(-2) year(-1) but was estimated to be 170.2 Mg km(-2) year(-1). The close match between the sediment amounts estimated using the RUSLE

Linked Orders Improve Safety in Scheduling and Administration of Chemotherapeutic Agents

PubMed Central

Whipple, Nancy; Boulware, Joy; Danca, Kala; Boyarin, Kirill; Ginsberg, Eliot; Poon, Eric; Sweet, Micheal; Schade, Sue; Rogala, Jennifer

2010-01-01

The pharmacologic treatment for cancer must adhere to complex, finely orchestrated treatment plans, including not only chemotherapy medications, but pre/post-hydration, anti-emetics, anti-anxiety, and other medications that are given before, during and after chemotherapy doses. The treatment plans specify the medications and dictate precise dosing, frequency, and timing. This is a challenge to most Computerized Physician Order Entry (CPOE), Pharmacy and Electronic Medication Administration record (eMAR) Systems. Medications are scheduled on specific dates, referred to as chemo days, from the onset of the treatment, and precisely timed on the designated chemo day. For patients enrolled in research protocols, the adherence to the defined schedule takes on additional import, since variation is a violation of the protocol. If the oncologist determines that medications must be administered outside the defined constraints, the patient must be un-enrolled from the protocol and the course of therapy is re-written. Pharmacy and eMAR systems utilized in processing chemotherapy medications must be able to support the intricate relationships between each drug defined in the treatment plans. PMID:21347104

Role of the area postrema in three putative measures of motion sickness in the rat

NASA Technical Reports Server (NTRS)

Sutton, Richard L.; Fox, Robert A.; Daunton, Nancy G.

1991-01-01

After thermal cauterization of the area postrema in rats, the absence of conditioned taste aversion of sucrose paired with lithium chloride (0.15M, 3.3 ml/kg) was used as a pharmacologic/behavioral index of area postrema damage. In a subsequent experiment the effects of area postrema lesions on three measures proposed as species-relevant measures of motion sickness were studied, using off-vertical rotation at 150 deg/s for either 30 or 90 min. Lesions of area postrema did not alter postrotational suppression of drinking or amount of defecation during motion. The initial acquisition of conditioned taste aversion to a novel cider vinegar solution paired with motion was not affected by lesioning of the area postrema, but these taste aversions extinguished more slowly in lesioned rats than in sham-operates or intact controls. Results are discussed in terms of proposed humoral factors which may induce motion sickness and in light of recent data on the role of the area postrema in similar measures in species possessing the complete emetic reflex.

[Preventive efficacy of ondansetron and granisetron for postoperative nausea and vomiting in high risk patients].

PubMed

Quan, Xiang; Zhu, Bo; Ye, Tie-hu

2011-08-01

To compare the efficacy of ondansetron and granisetron in the prevention of postoperative nausea and vomiting (PONV) in high-risk patients. Totally 200 patients with three key risk factors for PONV (female, non-smoking and postoperative opioid use) were equally randomized into ondansetron group and granisetron group. Ondansetron (4 mg) or granisetron (3 mg) was intravenously administered upon the completion of surgery. The episodes of nausea and vomiting were observed for 24 hours after surgery. A significantly greater proportion of patients in granisetron group achieved a complete response (i.e., no PONV or rescue medication) during the first 24 hours postoperatively versus those in ondansetron group (62.6% vs. 46.9%, respectively; P=0.048). There were no significant differences in terms of postoperative nausea incidences (42.9% vs. 34.3%, respectively), postoperative vomiting incidences (25.5% vs. 20.2%, respectively) and postoperative rescue anti-emetics incidences (19.4% vs. 15.2%, respectively) (P>0.05). Granisetron is more effective than ondansetron in preventing PONV in high-risk patients during the first 24 hours postoperatively.

Lessons learnt from a birthday party: a Bacillus cereus outbreak, Bari, Italy, January 2012.

PubMed

Martinelli, Domenico; Fortunato, Francesca; Tafuri, Silvio; Cozza, Vanessa; Chironna, Maria; Germinario, Cinzia; Pedalino, Biagio; Prato, Rosa

2013-01-01

Bacillus cereus, a ubiquitous bacterium, can be isolated in various starchy food items, causing both emetic and diarrhoeal disease. The real burden of B. cereus outbreaks is actually poorly known in Italy. We report a B. cereus foodborne outbreak that occurred in a pub in Bari (Italy) on January 22nd 2012 during a birthday party, promptly reported by the pub owner. Between January 22nd and 24th 2012, we performed a retrospective cohort study among the guests of the party to identify risk factors associated with illness. Leftovers of different meals were available for microbiological analysis. Faecal specimens were collected from cases. A total of 12 cases among the 13 customers (attack rate: 92%) were reported. All cases had consumed basmati rice and sweet and sour vegetables (aetiological fraction: 100%). B. cereus was isolated from both basmati rice served during the party and faecal specimens. The close collaboration between the pub owner and the public health officers and the possibility to test food leftovers and stool samples contributed to prevent further cases.

Rotavirus infection

PubMed Central

Crawford, Sue E.; Ramani, Sasirekha; Tate, Jacqueline E.; Parashar, Umesh D.; Svensson, Lennart; Hagbom, Marie; Franco, Manuel A.; Greenberg, Harry B.; O’Ryan, Miguel; Kang, Gagandeep; Desselberger, Ulrich; Estes, Mary K.

2017-01-01

Rotavirus infections are a leading cause of severe, dehydrating gastroenteritis in children <5 years of age. Despite the global introduction of vaccinations for rotavirus over a decade ago, rotavirus infections still result in >200,000 deaths annually, mostly in low-income countries. Rotavirus primarily infects enterocytes and induces diarrhoea through the destruction of absorptive enterocytes (leading to malabsorption), intestinal secretion stimulated by rotavirus non-structural protein 4 and activation of the enteric nervous system. In addition, rotavirus infections can lead to antigenaemia (which is associated with more severe manifestations of acute gastroenteritis) and viraemia, and rotavirus can replicate in systemic sites, although this is limited. Reinfections with rotavirus are common throughout life, although the disease severity is reduced with repeat infections. The immune correlates of protection against rotavirus reinfection and recovery from infection are poorly understood, although rotavirus-specific immunoglobulin A has a role in both aspects. The management of rotavirus infection focuses on the prevention and treatment of dehydration, although the use of antiviral and anti-emetic drugs can be indicated in some cases. PMID:29119972

Phytochemical and pharmacological review of Lagenaria sicereria

PubMed Central

Prajapati, Rakesh P.; Kalariya, Manisha; Parmar, Sachin K.; Sheth, Navin R.

2010-01-01

Lagenaria siceraria (Molina) standley (LS) (Family: Cucurbitaceae) is an annual herbaceous climbing plant with a long history of traditional medicinal uses in many countries, especially in tropical and subtropical regions. Since ancient times the climber has been known for its curative properties, and has been utilized for treatment of various ailments, including jaundice, diabetes, ulcer, piles, colitis, insanity, hypertension, congestive cardiac failure (CCF), and skin diseases. Its fruit pulp is used both as an emetic and purgative, and for its cooling, diuretic, antibilious, and pectoral properties. Boiled in oil this pulp is used to treat rheumatism and insomnia. A wide range of chemical compounds including sterols, terpenoids, flavonoids, and saponins have been isolated from the species. Its extracts have been found to possess various pharmacological activities. Below, we give a comprehensive review of its ethnomedical uses, chemical constituents, and pharmacological profile as a medicinal plant. Particular attention is given to its analgesic, anti-inflammatory, antihyperlipidemic, diuretic, hepatoprotective, anthelmintic, and antibacterial effects so that its potential uses in pharmaceutics can be better evaluated. PMID:21731373

The Many Faces of Apomorphine: Lessons from the Past and Challenges for the Future.

PubMed

Auffret, Manon; Drapier, Sophie; Vérin, Marc

2018-06-01

Apomorphine is now recognized as the oldest antiparkinsonian drug on the market. Though still underused, it is increasingly prescribed in Europe for patients with advanced Parkinson's disease (PD) with motor fluctuations. However, its history is far from being limited to movement disorders. This paper traces the history of apomorphine, from its earliest empirical use, to its synthesis, pharmacological development, and numerous indications in human and veterinary medicine, in light of its most recent uses and newest challenges. From shamanic rituals in ancient Egypt and Mesoamerica, to the treatment of erectile dysfunction, from being discarded as a pharmacological tool to becoming an essential antiparkinsonian drug, the path of apomorphine in the therapeutic armamentarium has been tortuous and punctuated by setbacks and groundbreaking discoveries. Throughout history, three main clinical indications stood out: emetic (gastric emptying, respiratory disorders, aversive conditioning), sedative (mental disorders, clinical anesthesia, alcoholism), and antiparkinsonian (fluctuations). New indications may arise in the future, both in PD (palliative care, nonmotor symptoms, withdrawal of oral dopaminergic medication), and outside PD, with promising work in neuroprotection or addiction.

Controlled delivery of metoclopramide using an injectable semi-solid poly(ortho ester) for veterinary application.

PubMed

Schwach-Abdellaoui, Khadija; Moreau, Marinette; Schneider, Marc; Boisramć, Bernard; Gurny, Robert

2002-11-06

In animal health care, current therapeutic regimens for gastrointestinal disorders require repeated oral or parenteral dosage forms of anti-emetic agents. However, fluctuations of plasma concentrations produce severe side effects. The aim of this work is to develop a subcutaneous and biodegradable controlled release system containing metoclopramide (MTC). Semi-solid poly(ortho ester)s (POE) prepared by a transesterification reaction between trimethyl orthoacetate and 1,2,6,-hexanetriol were investigated as injectable bioerodible polymers for the controlled release of MTC. MTC is present in the polymeric matrix as a solubilised form and it is released rapidly from the POE by erosion and diffusion because of its acidic character and its high hydrosolubility. If a manual injection is desired, only low molecular weight can be used. However, low molecular weight POEs release the drug rapidly. In order to extend polymer lifetime and decrease drug release rate, a sparingly water-soluble base Mg(OH)(2) was incorporated to the formulation. It was possible to produce low molecular weight POE that can be manually injected and releasing MTC over a period of several days.

Acute cholestatic hepatitis caused by amoxicillin/clavulanate

PubMed Central

Beraldo, Daniel Oliveira; Melo, Joanderson Fernandes; Bonfim, Alexandre Vidal; Teixeira, Andrei Alkmim; Teixeira, Ricardo Alkmim; Duarte, André Loyola

2013-01-01

Amoxicillin/clavulanate is a synthetic penicillin that is currently commonly used, especially for the treatment of respiratory and cutaneous infections. In general, it is a well-tolerated oral antibiotic. However, amoxicillin/clavulanate can cause adverse effects, mainly cutaneous, gastrointestinal, hepatic and hematologic, in some cases. Presented here is a case report of a 63-year-old male patient who developed cholestatic hepatitis after recent use of amoxicillin/clavulanate. After 6 wk of prolonged use of the drug, he began to show signs of cholestatic icterus and developed severe hyperbilirubinemia (total bilirubin > 300 mg/L). Diagnostic investigation was conducted by ultrasonography of the upper abdomen, serum tests for infection history, laboratory screening of autoimmune diseases, nuclear magnetic resonance (NMR) of the abdomen with bile duct-NMR and transcutaneous liver biopsy guided by ultrasound. The duration of disease was approximately 4 mo, with complete resolution of symptoms and laboratory changes at the end of that time period. Specific treatment was not instituted, only a combination of anti-emetic (metoclopramide) and cholestyramine for pruritus. PMID:24379601

Acute cholestatic hepatitis caused by amoxicillin/clavulanate.

PubMed

Beraldo, Daniel Oliveira; Melo, Joanderson Fernandes; Bonfim, Alexandre Vidal; Teixeira, Andrei Alkmim; Teixeira, Ricardo Alkmim; Duarte, André Loyola

2013-12-14

Amoxicillin/clavulanate is a synthetic penicillin that is currently commonly used, especially for the treatment of respiratory and cutaneous infections. In general, it is a well-tolerated oral antibiotic. However, amoxicillin/clavulanate can cause adverse effects, mainly cutaneous, gastrointestinal, hepatic and hematologic, in some cases. Presented here is a case report of a 63-year-old male patient who developed cholestatic hepatitis after recent use of amoxicillin/clavulanate. After 6 wk of prolonged use of the drug, he began to show signs of cholestatic icterus and developed severe hyperbilirubinemia (total bilirubin > 300 mg/L). Diagnostic investigation was conducted by ultrasonography of the upper abdomen, serum tests for infection history, laboratory screening of autoimmune diseases, nuclear magnetic resonance (NMR) of the abdomen with bile duct-NMR and transcutaneous liver biopsy guided by ultrasound. The duration of disease was approximately 4 mo, with complete resolution of symptoms and laboratory changes at the end of that time period. Specific treatment was not instituted, only a combination of anti-emetic (metoclopramide) and cholestyramine for pruritus.

Pre-exposure to cocaine or morphine attenuates taste avoidance conditioning in adolescent rats: Drug specificity in the US pre-exposure effect.

PubMed

Clasen, Matthew M; Hempel, Briana J; Riley, Anthony L

2017-05-01

Although the attenuating effects of drug history on conditioned taste avoidance (CTA) learning have been widely investigated in adults, such effects in adolescents have not been well characterized. Recent research has suggested that the display of the drug pre-exposure effect during adolescence may be drug dependent given that pre-exposure to ethanol attenuates subsequent conditioning, whereas pre-exposure to the classic emetic lithium chloride (LiCl) fails to do so. The present study began investigating the possible drug-dependent nature of the effects of drug pre-exposure by pre-exposing and conditioning adolescent male Sprague-Dawley rats to drugs from two additional classes, specifically psychostimulants (cocaine; Experiment 1) and opioids (morphine; Experiment 2). Consistent with prior work with ethanol (but not LiCl), prior exposure to both cocaine and morphine attenuated taste avoidance induced by these compounds. Although this work supports the view of drug-dependent pre-exposure effects on taste avoidance learning during adolescence, research is needed to assess its mechanisms. © 2017 Wiley Periodicals, Inc.

Pharmacodynamic and pharmacokinetic effects of the intravenous CB1 receptor agonist Org 26828 in healthy male volunteers.

PubMed

Zuurman, Lineke; Passier, Paul C C M; de Kam, Marieke L; Kleijn, Huub J; Cohen, Adam F; van Gerven, Joop M A

2010-11-01

An ideal drug for outpatient treatments under conscious sedation would have both sedative and analgesic properties. CB1/CB2 agonists are expected to have sedative, amnestic, analgesic and anti-emetic properties. The main objective of this first study in humans was to assess the sedative properties of intravenous Org 26828. In addition, pharmacokinetics, amnestic properties, postural stability, and behavioural and cardiovascular effects were studied. Midazolam intravenous 0.1 mg/kg and placebo were used as controls. The pharmacokinetic parameters (Cmax and AUC0-inf) of the main metabolite Org 26761 were proportional to dose. No effects were observed after doses up to 0.3 μg/kg of Org 26828. Dose-related effects were observed at higher doses. Although subjects reported subjective sedation after administration of Org 26828 at 3 and 6 μg/kg, the observed sedation was considerably less than after midazolam. Doses higher than the maximum tolerated dose of 1 μg/kg of Org 26828 caused unpleasant central nervous system effects (anxiety, paranoia, hallucinations). Therefore, Org 26828 is not suitable for providing sedation for outpatient surgical procedures.

The use of emergency contraception in Australasian emergency departments.

PubMed

Millar, J R; Leach, D S; Maclean, A V; Kovacs, G T

2001-09-01

To review the prescribing of emergency contraception by emergency departments in Australasia and compare it with other providers. A postal questionnaire was sent to the director of each of the 79 Australasian College for Emergency Medicine accredited emergency departments in Australasia inquiring about the availability and prescribing habits for emergency contraception within each department. Of the 79 emergency departments, 69 (87.3%) responded to the questionnaire and were aware of the 'emergency contraception regimen'. The majority of departments prescribed appropriately (56%) and only one department did not arrange adequate follow up. Anti-emetics are always used by 45 departments (78.9%). Discussion of future contraceptive needs at the time of presentation was only undertaken by 25 departments (43.9%). Written clinical guidelines for emergency contraception were present in 28 departments (40.6%). Emergency departments are accessed by patients requesting contraception following unprotected intercourse or contraceptive failure. The prescribing of emergency contraception in Australasian emergency departments is comparable with other providers but substantial improvements could be made. Suggestions to assist this improvement include written clinical guidelines and patient information and purpose-made medication packs.

Tethered-restraint system for blood collection from ferrets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jackson, R.K.; Kieffer, V.A.; Sauber, J.S.

The laboratory ferret, Mustela putorius furo, recently has come into prominence as a laboratory animal for use in biomedical research. This laboratory has adopted the use of this species because the ferret's emetic response to radiation occurs at a lower dose and has a more rapid onset than that of dogs. One approach for determining the physiological basis of this response is to measure serum levels of various circulating substances before and after irradiation. However, blood collection from the ferret can be difficult because the lack of easily accessible veins and seasonal accumulation of subcutaneous body fat. This report describesmore » a method of tethered-restraint for the ferret in which an in-dwelling venous jugular catheter is implanted for withdrawing blood samples. No interference with the animal's normal activities occurs during the sampling procedure. Each animal is conditioned to the tethered-restraint prior to surgical placement of the catheter. The technique provides a minimally stressful method of restraint. A similar tethering system has been used successfully on several other animal species, such as non-human primates and rats.« less

Effects of zacopride and BMY25801 (batanopride) on radiation-induced emesis and locomotor behavior in the ferret

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, G.L.; Landauer, M.R.

1990-01-01

The antiemetic and locomotor effects of two substituted benzamides, zacopride and batanopride (BMY25801), were compared in ferrets after bilateral Co irradiation at 2, 4, or 6 Gy. Both zacopride and BMY25801 were effective against emesis and related signs. Zacopride, tested at several doses (0.003, 0.03 and 0.3 mg/kg), appeared to be more potent because it abolished emesis at 100-fold lower doses than did BMY25801 (3mg/kg). The ED value for the antiemetic effect of zacopride was 0.026 mg/kg (confidence levels = 0.0095, 0.072 mg/kg). However, analysis of emetic parameters recorded from vomiting animals (e.g., latency to first emesis) demonstrated that BMY25801more » provided greater antiemetic protection in this population than zacopride without and apparent side effects. Locomotor activity was significantly depressed by both radiation (all doses) and zacopride alone (0.03 mg/kg and 0.3 mg/kg). BMY25801 alone did not affect locomotor activity, and protected against the radiation-induced locomotor decrement.« less

[The Effectiveness of Epidural Droperidol for Prophylaxis of Postoperative Nausea and Vomiting: A Comparative Study of Droperidol and Adrenaline].

PubMed

Toyonaga, Shinya; Shinozuka, Norihiro; Dobashi, Tamae; Iiyori, Nao; Sudo, Tomoko

2016-05-01

Intravenous droperidol has strong evidence for antiemetic efficacy in high risk patients for prevention of postoperative nausea and vomiting (PONV). However it is not clear whether continuous epidural administration of doroperidol prevent PONV. It has been reported that epidural adrenaline decreases PONV; therefore we prospectively compared the effectiveness of epidural droperidol and adrenaline for prophylaxis of PONV. Eighty-six patients were scheduled for abdominal gynecological surgery under general-epidural anesthesia in the study. Patients were randomly assigned to droperidol group or adrenaline group. We investigated the incidences of PONV, the frequency of using the antiemetics. There was no statistical difference between the groups. The incidences of PONV were 27.9% (doropeidol group) and 58.1% (adrenaline group), respectively (P = 0.0046). The frequency of the anti-emetics use were 18.6% and 41.9%, respectively (P = 0.0189). There was one patient who needed cancellation of continuous epidural administration for vomiting in adrenaline group, but no patient in doropeidol group. The results suggest that epidural droperidol effectively decreases PONV in high risk patients. However epidural adrenaline might be ineffective.

Cannabis-derived substances in cancer therapy--an emerging anti-inflammatory role for the cannabinoids.

PubMed

Liu, Wai M; Fowler, Daniel W; Dalgleish, Angus G

2010-11-01

Cannabinoids, the active components of the cannabis plant, have some clinical merit both as an anti-emetic and appetite stimulant in cachexic patients. Recently, interest in developing cannabinoids as therapies has increased following reports that they possess anti-tumour properties. Research into cannabinoids as anti-cancer agents is in its infancy, and has mainly focussed on the pro-apoptotic effects of this class of agent. Impressive anti-cancer activities have been reported; actions that are mediated in large part by disruptions to ubiquitous signalling pathways such as ERK and PI3-K. However, recent developments have highlighted a putative role for cannabinoids as anti-inflammatory agents. Chronic inflammation has been associated with neoplasia for sometime, and as a consequence, reducing inflammation as a way of impacting cancer presents a new role for these compounds. This article reviews the ever-changing relationship between cannabinoids and cancer, and updates our understanding of this class of agent. Furthermore, the relationship between chronic inflammation and cancer, and how cannabinoids can impact this relationship will be described.

Epidemiology, Clinical Characteristics, and Associations for Rome IV Functional Nausea and Vomiting Disorders in Adults.

PubMed

Aziz, Imran; Palsson, Olafur S; Whitehead, William E; Sperber, Ami D; Simrén, Magnus; Törnblom, Hans

2018-05-29

Functional nausea and vomiting disorders (FNVDs) are classified as chronic nausea and vomiting syndrome (CNVS) or cyclic vomiting syndrome (CVS) - CVS includes cannabinoid hyperemesis syndrome. We investigated the population prevalence of FNVDs, their characteristics, and associated factors. In the year 2015, an Internet cross-sectional health survey was completed by 5931 adults in the general populations of 3 English-speaking countries; 2100 participants were in the United States, Canada, or the United Kingdom. Quota-based sampling was used to generate demographically balanced and population-representative samples. The survey collected data on demographics, healthcare visits, medications, somatic symptom severity, quality of life, and symptom-based diagnostic criteria for Rome IV FNVDs as well as for irritable bowel syndrome and functional dyspepsia. Subsequent comparisons were made between Rome IV FNVD subjects and individuals without FNVDs (controls). Overall, 2.2% of the population (n=131) fulfilled symptom-based diagnostic criteria for Rome IV FNVDs - the United States (3%) had a greater prevalence than Canada (1.9%) or the United Kingdom (1.8%) (P=.02). The prevalence of CNVS was similar among the countries, ranging from 0.8% to 1.2%. However, the prevalence of CVS was higher in the United States (2%) than in Canada (0.7%) or the United Kingdom (1%) (P=.03). The proportion of subjects with CVS taking cannabis did not differ significantly among countries (P=.31), although the 7 cases of cannabinoid hyperemesis syndrome were in the United States. A significantly higher proportion of subjects with CVS reported a compulsive need for hot water bathing to alleviate emetic symptoms than subjects with CNVS (44% vs. 19%, P=.03); this behaviour was independent of cannabis but augmented by its use. Subjects with FNVDs had significantly greater health impairment and health care utilization than controls. On multivariate analysis, independent factors associated with FNVDs

A novel lipid nanoemulsion system for improved permeation of granisetron.

PubMed

Doh, Hea-Jeong; Jung, Yunjin; Balakrishnan, Prabagar; Cho, Hyun-Jong; Kim, Dae-Duk

2013-01-01

A new lipid nanoemulsion (LNE) system containing granisetron (GRN) was developed and its in vitro permeation-enhancing effect was evaluated using Caco-2 cell monolayers. Particle size, polydispersity index (PI) and stability of the prepared GRN-loaded LNE systems were also characterized. The mean diameters of prepared LNEs were around 50 nm with PI<0.2. Developed LNEs were stable at 4°C in the dark place over a period of 12 weeks. In vitro drug dissolution and cytotoxicity studies of GRN-loaded LNEs were performed. GRN-loaded LNEs exhibited significantly higher drug dissolution than GRN suspension at pH 6.8 for 2h (P<0.05). In vitro permeation study in Caco-2 cell monolayers showed that the LNEs significantly enhanced the drug permeation compared to GRN powder. The in vivo toxicity study in the rat jejunum revealed that the prepared GRN-loaded LNE was as safe as the commercial formulation (Kytril). These results suggest that LNE could be used as a potential oral liquid formulation of GRN for anti-emetic treatment on the post-operative and chemotherapeutic patients. Copyright © 2012 Elsevier B.V. All rights reserved.

Design and Optimization of Domperidone Fast Dissolving Tablet Using Central Composite Design.

PubMed

Shailendra, Bhatt; Shailendra, Mandge; Manish, Jaimini; Singh, Tanwar Yuveraj; Priti, Trivedi

2015-01-01

The main aim present work was to optimize fast dissolving tablet (FDT) formulation using response surface approach. The variables studied were sodium bicarbonate (X1), citric acid (X2), and superdisintegrant, Ac-Di-Sol (X3). The main aspect of present work was to develop FDT of Domperidone which possesses fast disintegration and high mechanical strength. It was found that the response was affected by all the three factors studied. The statistical models were successfully used to prepare FDT of Domperidone with fast disintegration (31.08 seconds) and adequate hardness (4.1 kg/cm(2)). Pharmacokinetic studies in rats showed statistically insignificant difference (p>0.05) between Domperidone fast dissolving tablet (DFDT) and market product. This concluded that optimized FDT is bioequivalent with the marketed formulation. The values of Tmax were found to be 0.5 h and 0.75 h for DFDT and reference product, respectively. Conditioned place aversion study was performed on Swiss Albino mice and the study showed the better anti emetic potency of optimized FDT in nauseated condition over market product (p<0.05). Thus, the present investigation conclusively demonstrates the potential role in terms of rapid disintegration and high mechanical strength.

Cannabinoid 2 (CB2) receptor agonism reduces lithium chloride-induced vomiting in Suncus murinus and nausea-induced conditioned gaping in rats.

PubMed

Rock, Erin M; Boulet, Nathalie; Limebeer, Cheryl L; Mechoulam, Raphael; Parker, Linda A

2016-09-05

We aimed to investigate the potential anti-emetic and anti-nausea properties of targeting the cannabinoid 2 (CB2) receptor. We investigated the effect of the selective CB2 agonist, HU-308, on lithium chloride- (LiCl) induced vomiting in Suncus murinus (S. murinus) and conditioned gaping (nausea-induced behaviour) in rats. Additionally, we determined whether these effects could be prevented by pretreatment with AM630 (a selective CB2 receptor antagonist/inverse agonist). In S. murinus, HU-308 (2.5, 5mg/kg, i.p.) reduced, but did not completely block, LiCl-induced vomiting; an effect that was prevented with AM630. In rats, HU-308 (5mg/kg, i.p.) suppressed, but did not completely block, LiCl-induced conditioned gaping to a flavour; an effect that was prevented by AM630. These findings are the first to demonstrate the ability of a selective CB2 receptor agonist to reduce nausea in animal models, indicating that targeting the CB2 receptor may be an effective strategy, devoid of psychoactive effects, for managing toxin-induced nausea and vomiting. Copyright © 2016 Elsevier B.V. All rights reserved.

[Methods of preventing phlebitis induced by infusion of fosaprepitant].

PubMed

Kohno, Emiko; Kanematsu, Sayaka; Okazaki, Satoshi; Ogata, Makoto; Kanemitsu, Meiko; Yamashita, Hiromi; Syuntou, Kaori; Sekita, Masako; Nishioka, Ryoko; Yoshida, Hideyuki

2015-03-01

At our hospital, we use aprepitant for nausea and vomiting when administering highly emetic anticancer agents, according to "Guidelines for the Appropriate Use of Antiemetic Agents" given by the Japan Society of Clinical Oncology. We initiated the intravenous administration of fosaprepitant for better compliance compared with aprepitant; however, we observed phlebitis after the infusion of fosaprepitant. Therefore, we investigated measures to reduce phlebitis associated with the infusion of fosaprepitant. For the first premedication, fosaprepitant (150 mg) was dissolved in 100 mL of saline and administered for 30 minutes; 1 of 2 patients showed grade 4 phlebitis. For the modified premedication, fosaprepitant, dexamethasone, and 5- HT(3) antagonist were dissolved in 100 mL of saline and administered for 30 minutes. The modified premedication was administered to a total of 27 patients; 5 patients developed mild phlebitis (grade 1), but infusion could be continued by treating their phlebitis with a hot pack. We used a combination of dexamethasone and 5-HT(3) antagonist with fosaprepitant as a modified premedication in order to avoid drug-induced vascular damage, which resulted in the pH decreasing to 6.20-7.55 (close to neutral) and a shorter infusion time.

DIFFUSIVE-Magnetoresistance(DMR) Proton(PMR)/Hydrogen-ion WATER: PRE-``Fert''/``Grunberg'' GMR[and CMR]: Quo-Vadis ``Honesty''???: PLAGIARISM!!!

NASA Astrophysics Data System (ADS)

Fart, Albart; Gruntbug, Peter; Siegel, Edward

2011-03-01

Proton/Hydrogen-ion Diffusive-Magnetoresistance(DMR) of Siegel[APS March-Mtgs.(70s)] based upon Siegel[Int'l. Conf. Mag.-Alloys and Oxides("ICMAO"), The Technion(77); J. Mag. Mag. Mtls. 7, 312(78)] FIRST experimental-discovery of GMR and FIRST theoretical prediction of CMR[ibid. 7, 338 (78)], facilitates NEW water production in global-warming exacerbated dry arid/semi-arid regions: Only HYDROGEN is/can be "FLYING-WATER"!!! (aka "chemical-rain-in-pipelines"). EMET/TRUTH-in-the-``SEANCES'', would-be "Sciences": C. Perelman-Corredoira [Against the Tide(07)] featuring Martin-Bradshaw ["Healing the SHAME That BINDS You"(80s)] systemic sociological-dysfunctionality(S-D), and Grigory Perelman's HEROIC ETHICS (refusal of both pure-maths Poincare-conjecture proof 2007 Fields-medal and 2010 Clay-Institute so-called/media-hyped/P.Red/spin-doctored millennium-prize million-dollar would-be award, militates as well in the current "SEANCE" of physics/maths politics/media-hype/P.R /spin-doctoring VS. Siegel FIRST experimental GMR a never-acknowledged full decade PRE-"Fert"(88) /"Grunberg(89)" ``Phales-GroPE''/Thompson-CSF/ KFZ-JEWlich 2007 physics Wolf/Japan/Nobel-prizes!!!

Identification of hemolysin BL-producing Bacillus cereus isolates by a discontinuous hemolytic pattern in blood agar.

PubMed Central

Beecher, D J; Wong, A C

1994-01-01

Bacillus cereus causes distinct exotoxin-mediated diarrheal and emetic food poisoning syndromes and a variety of nongastrointestinal infections. Evidence is accumulating that hemolysin BL is a major B. cereus virulence factor. We describe two methods for detection of hemolysin BL in crude samples and on primary culture media. In the first method, the highly unusual discontinuous hemolysis pattern that is characteristic of pure hemolysin BL was produced in sheep and calf blood agar around wells filled with crude culture supernatant from hemolysin BL-producing strains. In the second method, the pattern was formed surrounding colonies of hemolysin BL-producing strains grown on media consisting of nutrient agar, 0.15 M NaCl, 2% calf serum, and sheep or calf blood. Hemolysin BL production was detected with these methods in 41 of 62 (66%) previously identified B. cereus isolates and in 46 of 136 (34%) presumptive B. cereus isolates from soil. All nine isolates tested that were associated with diarrhea or nongastrointestinal illness were positive for hemolysin BL. The methods presented here are specific, simple, inexpensive, and applicable to the screening of large numbers of samples or isolates. Images PMID:8017944

Sensory and motor properties of the cerebellar uvula and modulus

NASA Technical Reports Server (NTRS)

Robinson, F. R.

1985-01-01

The uvula and nodulus (vermal lobules 9 and 10) of the vestibulocerebellum are implicated by behavioral evidence in the control of eye and head movements and in the production of motion sickness. The uvula and nodulus could play a role in these functions through known output pathways. Purkinje cells in both structures project via the fastigial and vestibular nuceli to the ventral horn of the cervical spin cord, to oculomotor neurons, and to the emetic region of the reticular formation (ablation of which abolishes susceptability to motion sickness). Uvula and nodulus Purkinje cells will be analyzed in cats trained to make controlled head movements. The activity of these neurons is expected to modulate well during head and/or eye movements because the uvula and nodulus receive heavy projections from sources of visual, vestibular and neck proprioceptive information. How neuron activity contributes to movement and how different sensory inputs converge to influence this contribution may be determined by characterizing movement related properties of these neurons. A population of neurons that modulates powerfully to the conflict between different head movement signals that can cause motion sickness may be identified.

Prevalence, isolation and characterization of Bacillus cereus strains from rice of local cultivators of Sabah, Sarawak, and Peninsular Malaysia

NASA Astrophysics Data System (ADS)

Sawei, Jelin; Sani, Norrakiah Abdullah

2016-11-01

Bacillus cereus is a spore-forming, facultative anaerobic, motile microorganism that has been identified as a causative agent of two types of gastrointestinal diseases such as emetic and diarrhea. This foodborne pathogen is found in both vegetative cells and endospores form in foods such as rice either raw or cooked. The aim of this study is to investigate and determine the prevalence, characterize and identify the isolation of vegetative cells and endospores of B. cereus in thirty varieties (n=3) of raw rice from Sabah, Sarawak and Peninsular Malaysia. A total of 90 (n=90) raw rice were examined and 84 (93.33%) samples were positive to vegetative cells of B. cereus. However, only 32 (35.56%) samples were positive for endospore cells that able to germinate after samples were heated at 75°C for 15 mins. The mean log cfu/g for vegetative cells were higher range (0.00 - 4.1533) than visible endospores (0.00 - 3.7533 mean log cfu/g). Sample of raw red rice (UKMRC9) had significantly higher contamination by both vegetative cells and endospores at p<0.05, than the other raw rice samples.

Rapid purification of staphylococcal enterotoxin B by high-pressure liquid chromatography.

PubMed Central

Strickler, M P; Neill, R J; Stone, M J; Hunt, R E; Brinkley, W; Gemski, P

1989-01-01

The Staphylococcus aureus enterotoxins represent a group of proteins that cause emesis and diarrhea in humans and other primates. We have developed a rapid two-step high-pressure liquid chromatography (HPLC) procedure for purification of staphylococcal enterotoxin B (SEB). Sterile filtrates (2.5 liters) of strain 10-275 were adsorbed directly onto a reversed-phase column (50 mm by 30 cm Delta Pak; 300 A [30 nm], 15 microns, C18). SEB was obtained by using a unique sequential gradient system. First, an aqueous ammonium acetate to acetonitrile gradient followed by an aqueous trifluoroacetic acid (TFA) wash was used to remove contaminants. A subsequent TFA to acetonitrile-TFA gradient eluted the bound SEB. Further purification was obtained by rechromatography on a cation-exchange column. From 35 to 45% of the SEB in starting filtrates was recovered. Analysis by immunoblotting of samples separated on sodium dodecyl sulfate-polyacrylamide gels indicated that HPLC-purified SEB exhibited immunological and biochemical properties similar to those of the SEB standard. Induction of an emetic response in rhesus monkeys showed that the HPLC-purified toxin also retained biological activity. Images PMID:2745678

[6]-gingerol induces electrogenic sodium absorption in the rat colon via the capsaicin receptor TRPV1.

PubMed

Tsuchiya, Yo; Fujita, Rina; Saitou, Akae; Wajima, Nanako; Aizawa, Fuyuka; Iinuma, Akane

2014-01-01

[6]-Gingerol possesses a variety of beneficial pharmacological and therapeutic properties, including anti-carcinogenic, anti-inflammatory, and anti-emetic activities. Although [6]-gingerol is known to regulate the contraction of the intestine, its effect on intestinal ion transport is unclear. The aim of this study was to examine the role of [6]-gingerol in the regulation of electrogenic ion transport in the rat intestine by measuring the transmural potential difference (ΔPD). [6]-Gingerol induced significant positive ΔPD when administered to the serosal but not mucosal side of the colon, ileum, and jejunum; the highest effect was detected in the colon at a concentration of 10 μM. [6]-Gingerol-induced increase in ΔPD was suppressed by ouabain, an inhibitor of Na(+)/K(+)-ATPase, whereas no effect was observed in response to bumetanide, an inhibitor of the Na(+)-K(+)-2Cl(-) co-transporter. In addition, ΔPD induction by [6]-gingerol was greatly diminished by capsazepine, an inhibitor of the capsaicin receptor TRPV1. These results suggest that [6]-gingerol induced the electrogenic absorption of sodium in the rat colon via TRPV1.

Overweight/obesity and gastric fluid characteristics in pediatric day surgery: implications for fasting guidelines and pulmonary aspiration risk.

PubMed

Cook-Sather, Scott D; Gallagher, Paul R; Kruge, Lydia E; Beus, Jonathan M; Ciampa, Brian P; Welch, Kevin Conor; Shah-Hosseini, Sina; Choi, Jieun S; Pachikara, Reshma; Minger, Kim; Litman, Ronald S; Schreiner, Mark S

2009-09-01

The safety of 2-h preoperative clear liquid fasts has not been established for overweight/obese pediatric day surgical patients. Healthy children and obese adults who fasted 2 h have small residual gastric fluid volumes (GFVs), which are thought to reflect low pulmonary aspiration risk. We sought to measure the prevalence of overweight/obesity in our day surgery population. We hypothesized that neither body mass index (BMI) percentile nor fasting duration would significantly affect GFV or gastric fluid pH. In children who were allowed clear liquids up until 2 h before surgery, we hypothesized that overweight/obese subjects would not have increased GFV over lean/normal subjects and that emesis/pulmonary aspiration events would be rare. Demographics, medical history, height, and weight were recorded for 1000 consecutive day surgery patients aged 2-12 yr. In addition, 1000 day surgery patients (age 2-12 yr) undergoing general endotracheal anesthesia were enrolled. After tracheal intubation, a 14-18F orogastric tube was inserted and gastric contents evacuated. Medications, fasting interval, GFV, pH, and emetic episodes were documented. Age- and gender-specific Center for Disease Control and Prevention growth charts (2000) were used to determine ideal body weight (IBW = 50th percentile) and to classify patients as lean/normal (BMI 25th-75th percentile), overweight (BMI > or = 85th to <95th percentile), or obese (BMI > or = 95th percentile). Of all day surgery patients, 14.0% were overweight and 13.3% were obese. Obese children had lower GFV per total body weight (P < 0.001). When corrected for IBW, however, volumes GFV(IBW) were identical across all BMI categories (mean 0.96 mL/kg, sd 0.71; median 0.86 mL/kg, IQR 0.96). Preoperative acetaminophen and midazolam contributed to increased GFV(IBW) (P = 0.025 and P = 0.001). Lower GFV(IBW) was associated with ASA physical status III (P = 0.024), male gender (P = 0.012), gastroesophageal reflux disease (P = 0.049), and proton

Diet of land birds along an elevational gradient in Papua New Guinea

PubMed Central

Sam, Katerina; Koane, Bonny; Jeppy, Samuel; Sykorova, Jana; Novotny, Vojtech

2017-01-01

Food preferences and exploitation are crucial to many aspects of avian ecology and are of increasing importance as we progress in our understanding of community ecology. We studied birds and their feeding specialization in the Central Range of Papua New Guinea, at eight study sites along a complete (200 to 3700 m a.s.l.) rainforest elevational gradient. The relative species richness and abundance increased with increasing elevation for insect and nectar eating birds, and decreased with elevation for fruit feeding birds. Using emetic tartar, we coerced 999 individuals from 99 bird species to regurgitate their stomach contents and studied these food samples. The proportion of arthropods in food samples increased with increasing elevation at the expense of plant material. Body size of arthropods eaten by birds decreased with increasing elevation. This reflected the parallel elevational trend in the body size of arthropods available in the forest understory. Body size of insectivorous birds was significantly positively correlated with the body size of arthropods they ate. Coleoptera were the most exploited arthropods, followed by Araneae, Hymenoptera, and Lepidoptera. Selectivity indexes showed that most of the arthropod taxa were taken opportunistically, reflecting the spatial patterns in arthropod abundances to which the birds were exposed. PMID:28276508

Diet of land birds along an elevational gradient in Papua New Guinea.

PubMed

Sam, Katerina; Koane, Bonny; Jeppy, Samuel; Sykorova, Jana; Novotny, Vojtech

2017-03-09

Food preferences and exploitation are crucial to many aspects of avian ecology and are of increasing importance as we progress in our understanding of community ecology. We studied birds and their feeding specialization in the Central Range of Papua New Guinea, at eight study sites along a complete (200 to 3700 m a.s.l.) rainforest elevational gradient. The relative species richness and abundance increased with increasing elevation for insect and nectar eating birds, and decreased with elevation for fruit feeding birds. Using emetic tartar, we coerced 999 individuals from 99 bird species to regurgitate their stomach contents and studied these food samples. The proportion of arthropods in food samples increased with increasing elevation at the expense of plant material. Body size of arthropods eaten by birds decreased with increasing elevation. This reflected the parallel elevational trend in the body size of arthropods available in the forest understory. Body size of insectivorous birds was significantly positively correlated with the body size of arthropods they ate. Coleoptera were the most exploited arthropods, followed by Araneae, Hymenoptera, and Lepidoptera. Selectivity indexes showed that most of the arthropod taxa were taken opportunistically, reflecting the spatial patterns in arthropod abundances to which the birds were exposed.

Odisolane, a Novel Oxolane Derivative, and Antiangiogenic Constituents from the Fruits of Mulberry (Morus alba L.).

PubMed

Lee, Seoung Rak; Park, Jun Yeon; Yu, Jae Sik; Lee, Sung Ok; Ryu, Ja-Young; Choi, Sang-Zin; Kang, Ki Sung; Yamabe, Noriko; Kim, Ki Hyun

2016-05-18

Mulberry, the fruit of Morus alba L., is known as an edible fruit and commonly used in Chinese medicines as a warming agent and as a sedative, tonic, laxative, odontalgic, expectorant, anthelmintic, and emetic. Systemic investigation of the chemical constituents of M. alba fruits led to the identification of a novel oxolane derivative, (R*)-2-((2S*,3R*)-tetrahydro-2-hydroxy-2-methylfuran-3-yl)propanoic acid (1), namely, odisolane, along with five known heterocyclic compounds (2-6). The structure of the new compound was elucidated on the basis of HR-MS, 1D and 2D NMR ((1)H-(1)H COSY, HSQC, HMBC, and NOESY) data analysis. Compound 1 has a novel skeleton that consists of 8 carbon units with an oxolane ring, which until now has never been identified in natural products. The isolated compounds were subjected to several activity tests to verify their biological function. Among them, compounds 1, 3, and 5 significantly inhibited cord formation in HUVECs. The action mechanism of compound 3, which had the strongest antiangiogenic activity, was mediated by decreasing VEGF, p-Akt, and p-ERK protein expression. These results suggest that compounds isolated from M. alba fruits might be beneficial in antiangiogenesis therapy for cancer treatment.

Monastic incorporation of classical botanic medicines into the Renaissance pharmacopeia.

PubMed

Petrucelli, R J

1994-01-01

Ancient Greek physicians believed that health resulted from a balance of natural forces. Many, including Dioscorides, made compilations of plants and medicines derived from them, giving prominence to diuretics, cathartics and emetics. During the Roman Empire, although Greek physicians were highly valued, the Roman matron performed many medical functions and magic and astrology were increasingly used. In Judaic and later Christian societies disease was equated with divine disfavor. After the fall of Rome, the classical Greek medical texts were mainly preserved in Latin translation by the Benedictine monasteries, which were based around a patient infirmary, a herb garden and a library. Local plants were often substituted for the classical ones, however, and the compilations became confused and inaccurate. Greek medicine survived better in the remains of the Eastern Roman Empire, and benefitted from the influence of Arab medicine. Intellectual revival, when it came to Europe, did so on the fringes of the Moslem world, and Montpellier and Salerno were among the first of the new medical centers. Rather than relying on ancient experts, the new experimental method reported the tested effects of substances from identified plants. This advance was fostered by the foundation of universities and greatly aided by the later invention of the printing press, which also allowed wider dissemination of the classical texts.

Bacteriocin-like inhibitor substances produced by Mexican strains of Bacillus thuringiensis.

PubMed

Barboza-Corona, J Eleazar; Vázquez-Acosta, Herminia; Bideshi, Dennis K; Salcedo-Hernández, Rubén

2007-02-01

Bacteriocins are antimicrobial peptides synthesized and secreted by bacteria and could potentially be used as natural food preservatives. Here, we report the production of bacteriocin-like inhibitor substances (Bt-BLIS) by five Mexican strains of Bacillus thuringiensis. Bacillus thuringiensis subsp. morrisoni (LBIT 269), B. thuringiensis subsp. kurstaki (LBIT 287), B. thuringiensis subsp kenyae (LBIT 404), B. thuringiensis subsp. entomocidus (LBIT 420) and B. thuringiensis subsp. tolworthi (LBIT 524) produced proteinaceous Bt-BLIS with high levels of activity against Bacillus cereus and other gram-positive bacteria. Although none was active against the gram-negative bacteria, Escherichia coli, Shigella species and Pseudomonas aeruginosa, the five Bt-BLIS demonstrated antimicrobial activity against Vibrio cholerae, the etiologic agent of cholera. Biochemical and biophysical studies demonstrated that the five Bt-BLIS could be categorized into two groups, those produced by LBIT 269 and 287 (Group A) and LBIT 404, 420, 524 (Group B), based on relative time of peptide synthesis, distinctive bacterial target specificity and stability in a wide range of temperatures and pH. Because of their stability and bactericidal activities against B. cereus and V. cholerae agents of emetic, diarrheal and lethal syndromes in humans, these Bt-BLIS could potentially be used as biodegradable preservatives in the food industry.

Blockade of 5-hydroxytryptamine3 receptors prevents cisplatin-induced but not motion- or xylazine-induced emesis in the cat

NASA Technical Reports Server (NTRS)

Lucot, J. B.

1989-01-01

5-Hydroxytryptamine3 antagonists have been reported to prevent emesis elicited by cisplatin and radiation. This study investigated the possibility that drugs with this mechanism of action may be useful in preventing emesis elicited by other stimuli. The drugs ICS 205-930 (0.1 and 1.0 mg/kg) and MDL 72222 (0.1 and 1.0 mg/kg) were administered SC to cats before challenging them with either provocative motion or an emetic dose of xylazine. In no instance was a significant reduction in emesis evident. Zacopride was also administered before motion testing (0.01 to 10.0 mg/kg) and found to not have efficacy. To test the possibility that species or route of administration were factors in the negative results, 1.0 mg/kg of ICS 205-930 was administered SC before IV infusion of 7.5 mg/kg of cisplatin. There was a total suppression of emesis for the duration of the six-hour observation periods. This result verifies other work which found 5-hydroxytryptamine3 antagonists to be effective in preventing emesis elicited by cancer chemotherapeutic treatments. However, there is no evidence that they are effective in other syndromes, such as motion sickness and xylazine-induced emesis.

Bacillus cereus-induced food-borne outbreaks in France, 2007 to 2014: epidemiology and genetic characterisation

PubMed Central

Glasset, Benjamin; Herbin, Sabine; Guillier, Laurent; Cadel-Six, Sabrina; Vignaud, Marie-Léone; Grout, Joel; Pairaud, Sylvie; Michel, Valérie; Hennekinne, Jacques-Antoine; Ramarao, Nalini; Brisabois, Anne

2016-01-01

The aim of this study was to identify and characterise Bacillus cereus from a unique national collection of 564 strains associated with 140 strong-evidence food-borne outbreaks (FBOs) occurring in France during 2007 to 2014. Starchy food and vegetables were the most frequent food vehicles identified; 747 of 911 human cases occurred in institutional catering contexts. Incubation period was significantly shorter for emetic strains compared with diarrhoeal strains A sub-panel of 149 strains strictly associated to 74 FBOs and selected on Coliphage M13-PCR pattern, was studied for detection of the genes encoding cereulide, diarrhoeic toxins (Nhe, Hbl, CytK1 and CytK2) and haemolysin (HlyII), as well as panC phylogenetic classification. This clustered the strains into 12 genetic signatures (GSs) highlighting the virulence potential of each strain. GS1 (nhe genes only) and GS2 (nhe, hbl and cytK2), were the most prevalent GS and may have a large impact on human health as they were present in 28% and 31% of FBOs, respectively. Our study provides a convenient molecular scheme for characterisation of B. cereus strains responsible for FBOs in order to improve the monitoring and investigation of B. cereus-induced FBOs, assess emerging clusters and diversity of strains. PMID:27934583

What to expect from immersive virtual environment exposure: influences of gender, body mass index, and past experience.

PubMed

Stanney, Kay M; Hale, Kelly S; Nahmens, Isabelina; Kennedy, Robert S

2003-01-01

For those interested in using head-coupled PC-based immersive virtual environment (VE) technology to train, entertain, or inform, it is essential to understand the effects this technology has on its users. This study investigated potential adverse effects, including the sickness associated with exposure and extreme responses (emesis, flashbacks). Participants were exposed to a VE for 15 to 60 min, with either complete or streamlined navigational control and simple or complex scenes, after which time measures of sickness were obtained. More than 80% of participants experienced nausea, oculomotor disturbances, and/or disorientation, with disorientation potentially lasting > 24 hr. Of the participants, 12.9% prematurely ended their exposure because of adverse effects; of these, 9.2% experienced an emetic response, whereas only 1.2% of all participants experienced emesis. The results indicate that designers may be able to reduce these rates by limiting exposure duration and reducing the degrees of freedom of the user's navigational control. Results from gender, body mass, and past experience comparisons indicated it may be possible to identify those who will experience adverse effects attributable to exposure and warn such individuals. Applications for this research include military, entertainment, and any other interactive systems for which designers seek to avoid adverse effects associated with exposure.

Novel method of determination of D9-tetrahydrocannabinol(THC) in human serum by high-performance liquid chromatography with electrochemical detection.

PubMed

Kokubun, Hideya; Uezono, Yasuhito; Matoba, Motohiro

2014-04-01

In Europe and the United States, D9-tetrahydrocannabinol(THC, dronabinol), one of the psychoactive constituents of cannabis, has been used for both its anti-emetic and orexigenic effects in cancer patient receiving chemotherapy.However, dronabinol has not yet been launched in the market in Japan.In the future, it is necessary to ascertain the pharmacokinetics of dronabinol in cancer paitient.Therefore, we developed an HPLC procedure using electrochemical detection(ECD)for quan- titation of the concentrations of dronabinol in blood.An eluent of 50mM KH2PO4/CH3CN(9:16)was used as the mobile phase.The column was used the XTerra®RP18, and the voltage of the electrochemical detector in dronabinol was set at 400 mV.As a result, the calibration curve was linear in the range of 10 ng/mL to 100 ng/mL(y=964.85x -3,419, r=0.997).The lower limit of quantification was 0.5 ng/mL(S/N=3).The relative within-runs and between-runs standard deviations for the assay dronabinol were less than 4.7%. The method reported here is superior to previously reported methods in cancer patient.

Plant compounds enhance the assay sensitivity for detection of active Bacillus cereus toxin.

PubMed

Rasooly, Reuven; Hernlem, Bradley; He, Xiaohua; Friedman, Mendel

2015-03-11

Bacillus cereus is an important food pathogen, producing emetic and diarrheal syndromes, the latter mediated by enterotoxins. The ability to sensitively trace and identify this active toxin is important for food safety. This study evaluated a nonradioactive, sensitive, in vitro cell-based assay, based on B. cereus toxin inhibition of green fluorescent protein (GFP) synthesis in transduced monkey kidney Vero cells, combined with plant extracts or plant compounds that reduce viable count of B. cereus in food. The assay exhibited a dose dependent GFP inhibition response with ~25% inhibition at 50 ng/mL toxin evaluated in culture media or soy milk, rice milk or infant formula, products associated with food poisonings outbreak. The plant extracts of green tea or bitter almond and the plant compounds epicatechin or carvacrol were found to amplify the assay response to ~90% inhibition at the 50 ng/mL toxin concentration greatly increasing the sensitivity of this assay. Additional studies showed that the test formulations also inhibited the growth of the B. cereus bacteria, likely through cell membrane disruption. The results suggest that the improved highly sensitive assay for the toxin and the rapid inactivation of the pathogen producing the toxin have the potential to enhance food safety.

Therapeutic orchids: traditional uses and recent advances--an overview.

PubMed

Hossain, Mohammad Musharof

2011-03-01

Orchids have been used as a source of medicine for millennia to treat different diseases and ailments including tuberculosis, paralysis, stomach disorders, chest pain, arthritis, syphilis, jaundice, cholera, acidity, eczema, tumour, piles, boils, inflammations, menstrual disorder, spermatorrhea, leucoderma, diahorrhea, muscular pain, blood dysentery, hepatitis, dyspepsia, bone fractures, rheumatism, asthma, malaria, earache, sexually transmitted diseases, wounds and sores. Besides, many orchidaceous preparations are used as emetic, purgative, aphrodisiac, vermifuge, bronchodilator, sex stimulator, contraceptive, cooling agent and remedies in scorpion sting and snake bite. Some of the preparations are supposed to have miraculous curative properties but rare scientific demonstration available which is a primary requirement for clinical implementations. Incredible diversity, high alkaloids and glycosides content, research on orchids is full of potential. Meanwhile, some novel compounds and drugs, both in phytochemical and pharmacological point of view have been reported from orchids. Linking of the indigenous knowledge to the modern research activities will help to discover new drugs much more effective than contemporary synthetic medicines. The present study reviews the traditional therapeutic uses of orchids with its recent advances in pharmacological investigations that would be a useful reference for plant drug researches, especially in orchids. Copyright © 2010 Elsevier B.V. All rights reserved.

Safety and efficacy of intravenous administration for tranexamic acid-induced emesis in dogs with accidental ingestion of foreign substances.

PubMed

Orito, Kensuke; Kawarai-Shimamura, Asako; Ogawa, Atsushi; Nakamura, Atsushi

2017-12-22

A prospective observational study was performed in canine clinical medicine to evaluate the emetic action and adverse effects of tranexamic acid. Veterinarians treated 137 dogs with a single dose of tranexamic acid (50 mg/kg, IV) after accidental ingestion of foreign substances. If needed, a second (median, 50 mg/kg; range, 20-50 mg/kg, IV) or third dose (median, 50 mg/kg; range, 25-50 mg/kg, IV) was administered. Tranexamic acid induced emesis in 116 of 137 (84.7%) dogs. Median time to onset of emesis was 116.5 sec (range, 26-370 sec), median duration of emesis was 151.5 sec (range, 30-780 sec), and median number of emesis episodes was 2 (range, 1-8). Second and third administrations of tranexamic acid induced emesis in 64.7 and 66.7% of dogs, respectively. In total, IV administration of tranexamic acid successfully induced emesis in 129 of 137 (94.2%) dogs. Adverse effects included a tonic-clonic convulsion and hemostatic disorder in two different dogs, both of which recovered after receiving medical care. Tranexamic acid induced emesis in most dogs following a single-dose. When a single dose was not sufficient, an additional dosage effectively induced emesis. Overall, adverse effects were considered low and self-limiting.

Antimicrobial activity in the common seawhip, Leptogorgia virgulata (Cnidaria: Gorgonaceae).

PubMed

Shapo, Jacqueline L; Moeller, Peter D; Galloway, Sylvia B

2007-09-01

Antimicrobial activity was examined in the gorgonian Leptogorgia virgulata (common seawhip) from South Carolina waters. Extraction and assay protocols were developed to identify antimicrobial activity in crude extracts of L. virgulata. Detection was determined by liquid growth inhibition assays using Escherichia coli BL21, Vibrio harveyii, Micrococcus luteus, and a Bacillus sp. isolate. This represents the first report of antimicrobial activity in L. virgulata, a temperate/sub-tropical coral of the western Atlantic Ocean. Results from growth inhibition assays guided a fractionation scheme to identify active compounds. Reverse-phase HPLC, HPLC-mass spectrometry, and 1H and 13C NMR spectroscopy were used to isolate, purify, and characterize metabolites in antimicrobial fractions of L. virgulata. Corroborative HPLC-MS/NMR evidence validated the presence of homarine and a homarine analog, well-known emetic metabolites previously isolated from L. virgulata, in coral extracts. In subsequent assays, partially-purified L. virgulata fractions collected from HPLC-MS fractionation were shown to contain antimicrobial activity using M. luteus and V. harveyii. This study provides evidence that homarine is an active constituent of the innate immune system in L. virgulata. We speculate it may act synergistically with cofactors and/or congeners in this octocoral to mount a response to microbial invasion and disease.

Bilious Vomiting Syndrome in Dogs: Retrospective Study of 20 Cases (2002-2012).

PubMed

Ferguson, Leah; Wennogle, Sara A; Webb, Craig B

2016-01-01

Bilious vomiting syndrome (BVS) is a condition historically associated with early morning vomiting of bile, but it is otherwise poorly characterized. The vomiting is thought to result from a reflux of duodenal fluid into the gastric lumen causing mucosal irritation. Medical records from Colorado State University Veterinary Teaching Hospital (CSUVTH) were searched for "canine" and "bilious vomiting syndrome" between 2002 and 2012. Visual inspection confirmed a diagnosis of BVS during the case history. The diagnosis remained BVS for the duration of the dog's contact with the hospital in 17 cases. Therapy involved frequent feedings, late evening meals, gastric acid reducers, prokinetics, and gastroprotectants. Twelve dogs improved with therapy. Five dogs did not improve or were lost to follow-up. The diagnosis of BVS was supplanted in three cases with gastric adenocarcinoma, dietary indiscretion, and hepatopathy. The patient most likely given a diagnosis of BVS would be a young, mixed-breed, castrated male dog with a chronic history of vomiting bile. Response to therapy suggests abnormal gastrointestinal motility, local gastritis, gastric pH, or stimulation of the emetic center may be important factors in BVS. Dogs diagnosed with BVS rarely received a diagnostic evaluation sufficient to qualify it as a diagnosis of exclusion.

Cisplatin-induced gastric dysrhythmia and emesis in dogs and possible role of gastric electrical stimulation.

PubMed

Yu, Xiaoyun; Yang, Jie; Hou, Xiaohua; Zhang, Kan; Qian, Wei; Chen, J D Z

2009-05-01

The aim of this study was to investigate the effect of cisplatin on gastric myoelectrical activity and the role of gastric electrical stimulation in the treatment of cisplatin-induced emesis in dogs. Seven dogs implanted with electrodes on the gastric serosa were used in a two-session study. Cisplatin was infused in both the control session and the gastric electrical stimulation session, and gastric electrical stimulation was applied in the gastric electrical stimulation session. Gastric slow waves and emesis, as well as behaviors suggestive of nausea, were recorded during each session. The results were as follows: (1) cisplatin induced vomiting and other symptoms and induced gastric dysrhythmia. The percentage of normal slow waves decreased significantly during the 2.5 h before vomiting (P=0.01) and the period of vomiting (P<0.001). (2) Gastric electrical stimulation reduced emesis and the symptoms score. The total score in the control session was higher than that in the gastric electrical stimulation session (P=0.02). However, gastric electrical stimulation had no effects on gastric dysrhythmia. It is concluded that cisplatin induces emesis and gastric dysrhythmia. Gastric electrical stimulation may play a role in relieving chemotherapy-induced emetic responses and deserves further investigation.

Intravenous glucagon in a deliberate insulin overdose in an adolescent with type 1 diabetes mellitus.

PubMed

White, Mary; Zacharin, Margaret R; Werther, George A; Cameron, Fergus J

2016-02-01

Massive insulin overdose may be associated with unpredictable and prolonged hypoglycemia. Concerns surrounding the potential provocation of insulin release from beta cells have previously prevented the use of intravenous glucagon as an adjunct to infusion of dextrose in this situation. We describe the case of a 15-yr-old boy with type 1 diabetes mellitus (T1DM) who presented with profound hypoglycemia following an overdose of an unknown quantity of premixed insulin. Owing to an increasing dextrose requirement and a dependence on hourly intramuscular glucagon injections, a continuous intravenous infusion of glucagon was commenced which successfully avoided the requirement for central venous access or concentrated dextrose infusion. Nausea was managed with anti-emetics. Intramuscular and subcutaneous glucagon is effective in the management of refractory and severe hypoglycemia in youth with both T1DM and hyperinsulinism. Concerns regarding the precipitation of rebound hypoglycemia with the use of intravenous glucagon do not relate to those with T1DM. This treatment option may be a useful adjunct in the management of insulin overdose in youth with T1DM and may avoid the requirement for invasive central venous access placement. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

New insights into selective PDE4D inhibitors: 3-(Cyclopentyloxy)-4-methoxybenzaldehyde O-(2-(2,6-dimethylmorpholino)-2-oxoethyl) oxime (GEBR-7b) structural development and promising activities to restore memory impairment.

PubMed

Brullo, Chiara; Ricciarelli, Roberta; Prickaerts, Jos; Arancio, Ottavio; Massa, Matteo; Rotolo, Chiara; Romussi, Alessia; Rebosio, Claudia; Marengo, Barbara; Pronzato, Maria Adelaide; van Hagen, Britt T J; van Goethem, Nick P; D'Ursi, Pasqualina; Orro, Alessandro; Milanesi, Luciano; Guariento, Sara; Cichero, Elena; Fossa, Paola; Fedele, Ernesto; Bruno, Olga

2016-11-29

Phosphodiesterase type 4D (PDE4D) has been indicated as a promising target for treating neurodegenerative pathologies such as Alzheimer's Disease (AD). By preventing cAMP hydrolysis, PDE4 inhibitors (PDE4Is) increase the cAMP response element-binding protein (CREB) phosphorylation, synaptic plasticity and long-term memory formation. Pharmacological and behavioral studies on our hit GEBR-7b demonstrated that selective PDE4DIs could improve memory without causing emesis and sedation. The hit development led to new molecule series, herein reported, characterized by a catechol structure bonded to five member heterocycles. Molecular modeling studies highlighted the pivotal role of a polar alkyl chain in conferring selective enzyme interaction. Compound 8a showed PDE4D3 selective inhibition and was able to increase intracellular cAMP levels in neuronal cells, as well as in the hippocampus of freely moving rats. Furthermore, 8a was able to readily cross the blood-brain barrier and enhanced memory performance in mice without causing any emetic-like behavior. These data support the view that PDE4D is an adequate molecular target to restore memory deficits in different neuropathologies, including AD, and also indicate compound 8a as a promising candidate for further preclinical development. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Gastroprokinetic effect of a new benzamide derivative itopride and its action mechanisms in conscious dogs.

PubMed

Iwanaga, Y; Miyashita, N; Saito, T; Morikawa, K; Itoh, Z

1996-06-01

The novel benzamide derivative itopride was assayed for its effect on gastrointestinal motility in conscious dogs when it was administered intraduodenally (i.d.). Gastrointestinal motility was measured by means of chronically implanted force transducers, and itopride at a dose of 10 mg/kg, i.d. or more increased the gastric contractile force during the digestive state. Intraduodenal cisapride, domperidone and metoclopramide also stimulated gastric motility, and their threshold doses were 1, 3 and 1 mg/kg, respectively. Dopamine infusion (1 mg/kg/hr, i.v.) caused the postprandial gastric motility to disappear, but it was immediately restored by itopride at a dose of 3 mg/kg, i.d. With itopride at 1 and 3 mg/kg, i.d., acetylcholine (0.05 mg/kg/min)-induced contractions were greatly enhanced. In addition to its gastric stimulation, itopride at doses of 10-100 mg/kg, p.o. inhibited apomorphine (0.1 mg/kg, s.c.)-induced vomiting in dogs. In conclusion, intraduodenal itopride stimulates gastric motility through both anti-dopaminergic and anti-acetylcholinesterase actions. Its gastroprokinetic threshold dose was as large as 3-10 times those of cisapride, domperidone and metoclopramide. These findings suggest that itopride is an orally active gastroprokinetic with a moderate anti-emetic action.

Comparing Nonsynergy Gamma Models and Interaction Models To Predict Growth of Emetic Bacillus cereus for Combinations of pH and Water Activity Values ▿

PubMed Central

Biesta-Peters, Elisabeth G.; Reij, Martine W.; Zwietering, Marcel H.; Gorris, Leon G. M.

2011-01-01

This research aims to test the absence (gamma hypothesis) or occurrence of synergy between two growth-limiting factors, i.e., pH and water activity (aw), using a systematic approach for model selection. In this approach, preset criteria were used to evaluate the performance of models. Such a systematic approach is required to be confident in the correctness of the individual components of the combined (synergy) models. With Bacillus cereus F4810/72 as the test organism, estimated growth boundaries for the aw-lowering solutes NaCl, KCl, and glucose were 1.13 M, 1.13 M, and 1.68 M, respectively. The accompanying aw values were 0.954, 0.956, and 0.961, respectively, indicating that equal aw values result in similar effects on growth. Out of the 12 models evaluated using the preset criteria, the model of J. H. T. Luong (Biotechnol. Bioeng. 27:280–285, 1985) was the best model to describe the effect of aw on growth. This aw model and the previously selected pH model were combined into a gamma model and into two synergy models. None of the three models was able to describe the combined pH and aw conditions sufficiently well to satisfy the preset criteria. The best matches between predicted and experimental data were obtained with the gamma model, followed by the synergy model of Y. Le Marc et al. (Int. J. Food Microbiol. 73:219–237, 2002). No combination of models that was able to predict the impact of both individual and combined hurdles correctly could be found. Consequently, in this case we could not prove the existence of synergy nor falsify the gamma hypothesis. PMID:21705525

An introduction to fast dissolving oral thin film drug delivery systems: a review.

PubMed

Kathpalia, Harsha; Gupte, Aasavari

2013-12-01

Many pharmaceutical companies are switching their products from tablets to fast dissolving oral thin films (OTFs). Films have all the advantages of tablets (precise dosage, easy administration) and those of liquid dosage forms (easy swallowing, rapid bioavailability). Statistics have shown that four out of five patients prefer orally disintegrating dosage forms over conventional solid oral dosages forms. Pediatric, geriatric, bedridden, emetic patients and those with Central Nervous System disorders, have difficulty in swallowing or chewing solid dosage forms. Many of these patients are non-compliant in administering solid dosage forms due to fear of choking. OTFs when placed on the tip or the floor of the tongue are instantly wet by saliva. As a result, OTFs rapidly hydrate and then disintegrate and/or dissolve to release the medication for local and/or systemic absorption. This technology provides a good platform for patent non- infringing product development and for increasing the patent life-cycle of the existing products. The application of fast dissolving oral thin films is not only limited to buccal fast dissolving system, but also expands to other applications like gastroretentive, sublingual delivery systems. This review highlights the composition including the details of various types of polymers both natural and synthetic, the different types of manufacturing techniques, packaging materials and evaluation tests for the OTFs.

Comparative trial of two intravenous doses of granisetron (1 versus 3 mg) in the prevention of chemotherapy-induced acute emesis: a double-blind, randomized, non-inferiority trial.

PubMed

Tsuji, Daiki; Kim, Yong-Il; Taku, Keisei; Nakagaki, Shigeru; Ikematsu, Yoshito; Tsubota, Hiromi; Maeda, Masato; Hashimoto, Naoya; Kimura, Masayuki; Daimon, Takashi

2012-05-01

A single 3 mg or 40 μg/kg intravenous dose of granisetron combined with dexamethasone is routinely used in several countries, although the antiemetic guidelines have recommended granisetron at the dose of 1 mg or 10 μg/kg. A randomized, multicenter trial was conducted to determine the optimal intravenous granisetron dose, 1 or 3 mg, in cancer patients receiving emetogenic chemotherapy. We enrolled 365 patients and randomly assigned them to receive intravenous granisetron 3 mg (3-mg group) or 1 mg (1-mg group), combined with dexamethasone at an adequate dose fixed as per the emetic risk category. The primary end point was the proportion of patients with a complete response during the first 24 h after chemotherapy. The study demonstrated that 1 mg of granisetron was not inferior in effect to 3 mg. For the primary end point, 359 patients were evaluable according to the modified intention-to-treat (ITT) analysis. Complete protection was achieved in the modified ITT population, 90.6% and 88.8% for the 3- and 1-mg groups, respectively (p < 0.01 for non-inferiority). This study showed that 1 mg granisetron is not inferior to 3 mg when both doses are combined with dexamethasone. Therefore, 1-mg dose of intravenous granisetron should be the recommended prophylactic regimen for the prevention of acute emesis.

Food-Borne Outbreak Investigation and Molecular Typing: High Diversity of Staphylococcus aureus Strains and Importance of Toxin Detection

PubMed Central

Denayer, Sarah; Nia, Yacine; Botteldoorn, Nadine

2017-01-01

Staphylococcus aureus is an important aetiological agent of food intoxications in the European Union as it can cause gastro-enteritis through the production of various staphylococcal enterotoxins (SEs) in foods. Reported enterotoxin dose levels causing food-borne illness are scarce and varying. Three food poisoning outbreaks due to enterotoxin-producing S. aureus strains which occurred in 2013 in Belgium are described. The outbreaks occurred in an elderly home, at a barbecue event and in a kindergarten and involved 28, 18, and six cases, respectively. Various food leftovers contained coagulase positive staphylococci (CPS). Low levels of staphylococcal enterotoxins ranging between 0.015 ng/g and 0.019 ng/g for enterotoxin A (SEA), and corresponding to 0.132 ng/g for SEC were quantified in the food leftovers for two of the reported outbreaks. Molecular typing of human and food isolates using pulsed-field gel electrophoresis (PFGE) and enterotoxin gene typing, confirmed the link between patients and the suspected foodstuffs. This also demonstrated the high diversity of CPS isolates both in the cases and in healthy persons carrying enterotoxin genes encoding emetic SEs for which no detection methods currently exist. For one outbreak, the investigation pointed out to the food handler who transmitted the outbreak strain to the food. Tools to improve staphylococcal food poisoning (SFP) investigations are presented. PMID:29261162

[The myth of virgin cleansing: Latest news on an archaic magico-religious practice].

PubMed

Charlier, P; Bou Abdallah, F; Brun, L; Hoang-Oppermann, V; Deo, S; Mostefai-Dulac, Y; Mamzer, M-F; Hervé, C

2018-03-01

In the medical anthropology section of the Nanterre Hospital (France) for migrants and refugees, three cases were recorded of "virgin cleansing" in sub-Saharan African countries. These consisted of sexual assaults (2 instances of rape and 1 of sexual interference) on sexually immature females (young girls) by patients with sexually transmitted infections (mainly HIV, syphilis) hoping they might thereby be cured. These particularly atrocious hetero-aggressive sexual practices based on magical arguments are unfortunately universal and are not limited to a specific culture. At the medical anthropology level, the belief in cleansing by virgins is based on the notion that the patient is dirty and impure. In the same way that emetics and/or laxatives are prescribed in the case of intestinal disorders (to "eliminate" the disease), some subjects use diuretics for urinary abnormalities or, literally, "clean vaginas (or anuses)" to purge their own miasma. The rising tide of population migrations (some of whom carry chronic infections), refugee camps, prolonged incarcerations, etc., makes observations of such phenomena increasingly frequent. Belief in cleansing by virgins (and the fatal consequences thereof) will be difficult to eradicate. The education of populations and health professionals should promote absolute respect for the body of children, and, more generally, of others, particularly since at this time of increasingly marked migratory flows, this problem sadly risks becoming widespread. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

What Is Nausea? A Historical Analysis of Changing Views

PubMed Central

Balaban, Carey D.; Yates, Bill J.

2016-01-01

The connotation of “nausea” has changed across several millennia. The medical term ‘nausea’ is derived from the classical Greek terms ναυτια and ναυσια, which designated the signs and symptoms of seasickness. In classical texts, nausea referred to a wide range of perceptions and actions, including lethargy and disengagement, headache (migraine), and anorexia, with an awareness that vomiting was imminent only when the condition was severe. However, some recent articles have limited the definition to the sensations that immediately precede emesis. Defining nausea is complicated by the fact that it has many triggers, and can build-up slowly or rapidly, such that the prodromal signs and symptoms can vary. In particular, disengagement responses referred to as the “sopite syndrome” are typically present only when emetic stimuli are moderately provocative, and do not quickly culminate in vomiting or disengagement from the triggering event. This review considers how the definition of “nausea” has evolved over time, and summarizes the physiological changes that occur prior to vomiting that may be indicative of nausea. Also described are differences in the perception of nausea, as well as the accompanying physiological responses, that occur with varying stimuli. This information is synthesized to provide an operational definition of nausea. PMID:27450627

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

PubMed

De Jonghe, Bart C; Holland, Ruby A; Olivos, Diana R; Rupprecht, Laura E; Kanoski, Scott E; Hayes, Matthew R

2016-01-01

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. Copyright © 2015 Elsevier Inc. All rights reserved.

Safety and efficacy of intravenous administration for tranexamic acid-induced emesis in dogs with accidental ingestion of foreign substances

PubMed Central

ORITO, Kensuke; KAWARAI-SHIMAMURA, Asako; OGAWA, Atsushi; NAKAMURA, Atsushi

2017-01-01

A prospective observational study was performed in canine clinical medicine to evaluate the emetic action and adverse effects of tranexamic acid. Veterinarians treated 137 dogs with a single dose of tranexamic acid (50 mg/kg, IV) after accidental ingestion of foreign substances. If needed, a second (median, 50 mg/kg; range, 20–50 mg/kg, IV) or third dose (median, 50 mg/kg; range, 25–50 mg/kg, IV) was administered. Tranexamic acid induced emesis in 116 of 137 (84.7%) dogs. Median time to onset of emesis was 116.5 sec (range, 26–370 sec), median duration of emesis was 151.5 sec (range, 30–780 sec), and median number of emesis episodes was 2 (range, 1–8). Second and third administrations of tranexamic acid induced emesis in 64.7 and 66.7% of dogs, respectively. In total, IV administration of tranexamic acid successfully induced emesis in 129 of 137 (94.2%) dogs. Adverse effects included a tonic-clonic convulsion and hemostatic disorder in two different dogs, both of which recovered after receiving medical care. Tranexamic acid induced emesis in most dogs following a single-dose. When a single dose was not sufficient, an additional dosage effectively induced emesis. Overall, adverse effects were considered low and self-limiting. PMID:29093310

Effects of acepromazine on the incidence of vomiting associated with opioid administration in dogs.

PubMed

Valverde, Alexander; Cantwell, Shauna; Hernández, Jorge; Brotherson, Celeste

2004-01-01

To evaluate the anti-emetic properties of acepromazine in dogs receiving opioids as pre-anesthetic medication. Randomized prospective clinical study. One hundred and sixteen dogs (ASA I or II), admitted for elective surgical procedures. The dogs were a mixed population of males and females, purebreds and mixed breeds, 0.25-13.4 years of age, weighing 1.8-57.7 kg. A prospective clinical trial in which the dogs were randomly assigned to one of three groups. All groups received acepromazine (0.05 mg kg(-1) intramuscularly (i.m.)). Group I received acepromazine 15 minutes prior to opioid administration. Group II received acepromazine in combination with the opioid. Group III received acepromazine 15 minutes after opioid administration. One of three different opioids was administered i.m. to each dog: morphine sulfate at 0.5 mg kg(-1); hydromorphone hydrochloride at 0.1 mg kg(-1); or oxymorphone hydrochloride at 0.075 mg kg(-1). Dogs receiving acepromazine before the opioid (group I) had a significantly lower incidence of vomiting (18%) than dogs in groups II (45%) and III (55%). The degree of sedation was significantly lower in the dogs receiving the combination of acepromazine and the opioid (group II) than in dogs receiving the opioid as the first drug (group III). Acepromazine administered 15 minutes before the opioid lowers the incidence of vomiting induced by opioids.

The Effect of a Standardized Ginger Extract on Chemotherapy-Induced Nausea-Related Quality of Life in Patients Undergoing Moderately or Highly Emetogenic Chemotherapy: A Double Blind, Randomized, Placebo Controlled Trial.

PubMed

Marx, Wolfgang; McCarthy, Alexandra L; Ried, Karin; McKavanagh, Dan; Vitetta, Luis; Sali, Avni; Lohning, Anna; Isenring, Elisabeth

2017-08-12

Ginger supplementation could be an effective adjuvant treatment for chemotherapy-induced nausea (CIN). The aim of this clinical trial was to address significant methodological limitations in previous trials. Patients (N = 51) were randomly allocated to receive either 1.2 g of standardised ginger extract or placebo per day, in addition to standard anti-emetic therapy, during the first three cycles of chemotherapy. The primary outcome was CIN-related quality of life (QoL) measured with the Functional Living Index- Emesis (FLIE) questionnaire. Secondary outcomes included acute and delayed nausea, vomiting, and retching as well as cancer-related fatigue, nutritional status, and CIN and vomiting-specific prognostic factors. Over three consecutive chemotherapy cycles, nausea was more prevalent than vomiting (47% vs. 12%). In chemotherapy Cycle 1, intervention participants reported significantly better QoL related to CIN ( p = 0.029), chemotherapy-induced nausea and vomiting (CINV)-related QoL ( p = 0.043), global QoL ( p = 0.015) and less fatigue ( p = 0.006) than placebo participants. There were no significant results in Cycle 2. In Cycle 3, global QoL ( p = 0.040) and fatigue ( p = 0.013) were significantly better in the intervention group compared to placebo. This trial suggests adjuvant ginger supplementation is associated with better chemotherapy-induced nausea-related quality of life and less cancer-related fatigue, with no difference in adverse effects compared to placebo.

Beer and wine in antiquity: beneficial remedy or punishment imposed by the Gods?

PubMed

Rosso, Ana Maria

2012-01-01

Different types of alcoholic beverages such as wine and beer were used in ancient times for various medicinal purposes. Being the oldest and probably the most widely used drugs, they were known to have some therapeutic value, in addition to the vital part they played in the daily life of people. Ethanol is produced by fermentation of a variety of plants and consumed either in a diluted form or concentrated by distillation to concoct alcoholic beverages. Beer made of fermented barley is an alcoholic drink that was believed to contain a spirit or a god. It is a drink of relatively low alcohol content with supernatural properties. The same was believed for wine. Considered to be divine, these beverages were the long sought elixirs of life and appeared in religious ceremonies, in mythology, and in social meals, such as the Greek symposia. In addition, these alcoholic drinks were considered to be a remedy for practically every disease and, therefore, were a common ingredient in ancient prescriptions. They were used as anaesthetics that dull the pain, as stimulants, as analgesics, as antiseptics to cleanse wounds and relieve pain, as emetics, as digestives, as antidotes for plant poisoning, for bites and stings, and as purifiers. However, we should not overlook the harmful effects of alcohol abuse such as drunkenness, chronic liver disease and, in modern terminology, infirmities that included pancreatitis, cardiomyopathy, peripheral neuropathy, dementia, and central nervous system disorders.

Serotonin-induced contractile responses of esophageal smooth muscle in the house musk shrew (Suncus murinus).

PubMed

Shiina, T; Naitou, K; Nakamori, H; Suzuki, Y; Horii, K; Sano, Y; Shimaoka, H; Shimizu, Y

2016-11-01

Serotonin (5-hydroxytryptamine, 5-HT) is a regulatory factor in motility of the gastrointestinal tract including the esophagus. Although we proposed that vagal cholinergic and mast cell-derived non-cholinergic components including serotonin coordinately shorten the esophagus, the precise mechanism of serotonin-induced contractions in the suncus esophagus is still unclear. Therefore, the aims of this study were to determine characteristics of contractile responses induced by serotonin and to identify 5-HT receptor subtypes responsible for regulating motility in the suncus esophagus. An isolated segment of the suncus esophagus was placed in an organ bath, and longitudinal or circular mechanical responses were recorded using a force transducer. Serotonin evoked contractile responses of the suncus esophagus in the longitudinal direction but not in the circular direction. Tetrodotoxin did not affect the serotonin-induced contractions. Pretreatment with a non-selective 5-HT receptor antagonist or double application of 5-HT 1 and 5-HT 2 receptor antagonists blocked the serotonin-induced contractions. 5-HT 1 and 5-HT 2 receptor agonists, but not a 5-HT 3 receptor agonist, evoked contractile responses in the suncus esophagus. The findings suggest that serotonin induces contractile responses of the longitudinal smooth muscle in the muscularis mucosae of the suncus esophagus that are mediated via 5-HT 1 and 5-HT 2 receptors on muscle cells. The serotonin-induced contractions might contribute to esophageal peristalsis and emetic response. © 2016 John Wiley & Sons Ltd.

Chemotherapy-induced nausea and vomiting in routine practice: a European perspective.

PubMed

Glaus, Agnes; Knipping, Cornelia; Morant, Rudolf; Böhme, Christel; Lebert, Burkhard; Beldermann, Frank; Glawogger, Bernhard; Ortega, Paz Fernandez; Hüsler, André; Deuson, Robert

2004-10-01

The aim of this study was to evaluate the occurrence of chemotherapy-induced nausea and vomiting (CINV) and its effect on patients' ability to carry out daily life activities following moderately to highly emetogenic, first-cycle chemotherapy in routine practice in cancer centers of four different European countries. This was a prospective, cross-sectional, nonrandomized, self-assessment study in 249 patients enrolled from cancer centers in Spain, Austria, Germany, and Switzerland. The study population consisted of 78% women, with a mean age of 54. Breast, lung, and ovarian cancers made up 75% of all cancers in the study. Patients received a mean of 2.0 chemotherapy agents and 2.5 antiemetic drugs. A total of 450 emetic episodes experienced by 243 patients was recorded over 5 days following chemotherapy, with an average of 1.8 episodes per patient (range: 0-28). A higher percentage of patients (38%) suffered from delayed compared to acute emesis (13%). Between 42% and 52% of all patients suffered from nausea (visual analogue scale > or = 5 mm) on any one day, peaking at day 3. Using the Functional Living Index for Emesis (FLIE) questionnaire, 75% of patients with nausea and 50% with vomiting reported a negative impact of these conditions on performance of daily living. CINV remains a significant problem in routine practice, particularly in the delayed phase posttreatment. Overall, CINV had a negative impact on patients' daily life.

Multi-element screening by ICP-MS of two specimens of Napoleon's hair.

PubMed

Kintz, Pascal; Ginet, Morgane; Cirimele, Vincent

2006-10-01

Since 1960, it has been demonstrated by various analytical procedures that high concentrations of arsenic were present in Napoleon's hair. Various authors, indicating that the detected arsenic levels are a consequence of external contamination, have challenged the results of these examinations. In order to shed more light on this historical controversy, we have tested two samples of Napoleon's hair by inductively coupled plasma-mass spectrometry (ICP-MS). The samples of hair were decontaminated with acetone and were cut into small segments. For multi-element screening, hair samples were mineralized in concentrated nitric acid for 1 h at 70 degrees C, diluted 1:40 in specific solution with rhodium as an internal standard, and finally analyzed by ICP-MS on a Thermo Electron ICP/MS X7. Multi-element analysis of Napoleon's hair samples revealed massive amounts of arsenic (42.1 and 37.4 ng/mg), antimony (2.1 and 1.8 ng/mg) and elevated levels of mercury (3.3 and 4.7 ng/mg) and lead (229 and 112 ng/mg). In the case of arsenic, these concentrations, 40 times higher than the normal values, confirm the hypothesis of a significant exposure to arsenic. The concentrations of the other elements, in particular antimony and mercury, are in agreement with the data already known about the therapeutic treatments given to Napoleon, which were based on calomel (salt of mercury) and tartar emetic (antimony).

Effects of 3,4-methylenedioxypyrovalerone (MDPV) pre-exposure on the aversive effects of MDPV, cocaine and lithium chloride: Implications for abuse vulnerability.

PubMed

Woloshchuk, Claudia J; Nelson, Katharine H; Rice, Kenner C; Riley, Anthony L

2016-10-01

Drug use is thought to be a balance of the rewarding and aversive effects of drugs. Understanding how various factors impact these properties and their relative balance may provide insight into their abuse potential. In this context, the present study attempted to evaluate the effects of drug history on the aversive effects of 3,4-methylenedioxypyrovalerone (MDPV), one of a variety of synthetic cathinones (collectively known as "bath salts"). Different groups of male Sprague-Dawley rats were exposed to either vehicle or MDPV (1.8mg/kg) once every fourth day for five total injections prior to taste avoidance conditioning in which a novel saccharin solution was repeatedly paired with either vehicle, MDPV (1.8mg/kg), the related psychostimulant cocaine (18mg/kg) or the emetic lithium chloride (LiCl) (13.65mg/kg). In animals pre-exposed to vehicle, all three drugs induced significant and comparable taste avoidance relative to animals injected with vehicle during conditioning. MDPV pre-exposure attenuated the avoidance induced by both MDPV and cocaine (greater attenuation for MDPV than cocaine), but had no effect on that induced by LiCl. These findings suggest that a history of MDPV use may reduce or attenuate MDPV and cocaine's (but not LiCl's) aversive effects. The implications for such changes in MDPV's aversive effects to its potential use and abuse were discussed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Dexamethasone Modifies Cystatin C-Based Diagnosis of Acute Kidney Injury During Cisplatin-Based Chemotherapy.

PubMed

Pianta, Timothy J; Pickering, John W; Succar, Lena; Chin, Melvin; Davidson, Trent; Buckley, Nicholas A; Mohamed, Fahim; Endre, Zoltan H

2017-01-01

Plasma cystatin C (pCysC) may be superior to serum creatinine (sCr) as a surrogate of GFR. However, the performance of pCysC for diagnosing acute kidney injury (AKI) after cisplatin-based chemotherapy is potentially affected by accompanying corticosteroid anti-emetic therapy and hydration. In a prospective observational study pCysC, sCr, urinary kidney injury molecule-1 (KIM-1), and urinary clusterin were measured over 2 weeks in 27 patients given first-cycle chemotherapy. The same variables were measured over 2 weeks in Sprague-Dawley rats given a single intraperitoneal injection of dexamethasone, cisplatin, or both, and in controls. In patients, pCysC increases were greater than sCr 41% vs. 16%, mean paired difference 25% (95% CI: 16-34%)], relative increases were ≥ 50% in 9 patients (35%) for pCysC compared with 2 (8%) for sCr (p = 0.04) and increases in sCr were accompanied by increased KIM-1 and clusterin excretion, but increases in pCysC alone were not. In rats, dexamethasone administration produced dose-dependent increases in pCysC (and augmented cisplatin-induced increases in pCysC), but did not augment histological injury, increases in sCr, or KIM-1 and clusterin excretion. In the presence of dexamethasone, elevation of pCysC does not reliably diagnose AKI after cisplatin-based chemotherapy. © 2017 The Author(s)Published by S. Karger AG, Basel.

The Rise, Fall and Subsequent Triumph of Thalidomide: Lessons Learned in Drug Development

PubMed Central

Rehman, Waqas; Arfons, Lisa M.; Lazarus, Hillard M.

2011-01-01

Perhaps no other drug in modern medicine rivals the dramatic revitalization of thalidomide. Originally marketed as a sedative, thalidomide gained immense popularity worldwide among pregnant women because of its effective anti-emetic properties in morning sickness. Mounting evidence of human teratogenicity marked a dramatic fall from grace and led to widespread social, legal and economic ramifications. Despite its tragic past thalidomide emerged several decades later as a novel and highly effective agent in the treatment of various inflammatory and malignant diseases. In 2006 thalidomide completed its remarkable renaissance becoming the first new agent in over a decade to gain approval for the treatment of plasma cell myeloma. The catastrophic collapse yet subsequent revival of thalidomide provides important lessons in drug development. Never entirely abandoned by the medical community, thalidomide resurfaced as an important drug once the mechanisms of action were further studied and better understood. Ongoing research and development of related drugs such as lenalidomide now represent a class of irreplaceable drugs in hematological malignancies. Further, the tragedies associated with this agent stimulated the legislation which revamped the FDA regulatory process, expanded patient informed consent procedures and mandated more transparency from drug manufacturers. Finally, we review recent clinical trials summarizing selected medical indications for thalidomide with an emphasis on hematologic malignancies. Herein, we provide a historic perspective regarding the up-and-down development of thalidomide. Using PubMed databases we conducted searches using thalidomide and associated keywords highlighting pharmacology, mechanisms of action, and clinical uses. PMID:23556097

Gastrinoma and Zollinger-Ellison syndrome in canids: a literature review and a case in a Mexican gray wolf.

PubMed

Struthers, Jason D; Robl, Nick; Wong, Valerie M; Kiupel, Matti

2018-06-01

Gastrinoma, an infrequent diagnosis in middle-aged dogs, occurs with nonspecific gastrointestinal morbidity. Laboratory tests can yield a presumptive diagnosis, but definitive diagnosis depends on histopathology and immunohistochemistry. We describe a malignant pancreatic gastrinoma with lymph node metastases and corresponding Zollinger-Ellison syndrome in a Mexican gray wolf ( Canis lupus baileyi) and review this endocrine neoplasm in domestic dogs. A 12-y-old, captive, male Mexican gray wolf developed inappetence and weight loss. Abdominal ultrasonography revealed a thickened duodenum and peritoneal effusion. Two duodenal perforations were noted on exploratory celiotomy and were repaired. Persisting clinical signs led to a second celiotomy that revealed a mesenteric mass, which was diagnosed histologically as a neuroendocrine carcinoma. During the following 16 mo, the wolf received a combination of H 2 -receptor antagonists, proton-pump inhibitors, gastroprotectants, and anti-emetics, but had recurrent episodes of anorexia, nausea, acid reflux, and remained underweight. Worsening clinical signs and weakness prompted euthanasia. The antemortem serum gastrin concentration of 414 ng/L (reference interval: 10-40 ng/L) corroborated hypergastrinemia. Autopsy revealed a mass expanding the right pancreatic limb; 3 parapancreatic mesenteric masses; duodenal ulcers; focal duodenal perforation with septic fibrinosuppurative peritonitis; chronic-active ulcerative esophagitis; and poor body condition. The pancreatic mass was diagnosed histologically as a neuroendocrine carcinoma and the parapancreatic masses as lymph node metastases. Immunohistochemistry of the pancreatic mass was positive for gastrin and negative for glucagon, insulin, pancreatic polypeptide, serotonin, somatostatin, and vasoactive intestinal peptide.

Gastric electrical stimulation with short pulses reduces vomiting but not dysrhythmias in dogs.

PubMed

Chen, Jiande D Z; Qian, Liwei; Ouyang, Hui; Yin, Jieyun

2003-02-01

The aim of this study was to investigate the acute effects of 3 different methods of electrical stimulation in the prevention of vasopressin-induced emetic response and gastric dysrhythmias. Seven female hound dogs chronically implanted with 4 pairs of electrodes on gastric serosa were used in a 5-session study. Saline and vasopressin were infused in sessions 1 and 2, respectively. In the other 3 sessions with vasopressin infusion, 3 different methods of electrical stimulation (short-pulse stimulation, long-pulse stimulation, and electroacupuncture) were applied. Gastric slow waves and vomiting and behaviors suggestive of nausea were recorded in each session. In a separate study, additional experiments were performed in 5 vagotomized dogs to investigate vagally mediated mechanisms. Vasopressin induced gastric dysrhythmias, uncoupling of slow waves, and vomiting and behaviors suggestive of nausea (P < 0.02, analysis of variance). Long-pulse stimulation, but not short-pulse stimulation or electroacupuncture, was capable of preventing vasopressin-induced gastric dysrhythmias and gastric slow wave uncoupling. Short-pulse stimulation and electroacupuncture, but not long-pulse stimulation, prevented vomiting and significantly reduced the symptom scores, which was not noted in the dogs with truncal vagotomy. Long-pulse stimulation normalizes vasopressin-induced slow wave abnormalities with no improvement in vomiting and behaviors suggestive of nausea. Short-pulse stimulation and electroacupuncture prevent vomiting and behaviors suggestive of nausea induced by vasopressin but have no effects on slow waves, and their effects are vagally mediated.

Biodiversity of aerobic endospore-forming bacterial species occurring in Yanyanku and Ikpiru, fermented seeds of Hibiscus sabdariffa used to produce food condiments in Benin.

PubMed

Agbobatinkpo, Pélagie B; Thorsen, Line; Nielsen, Dennis S; Azokpota, Paulin; Akissoe, Noèl; Hounhouigan, Joseph D; Jakobsen, Mogens

2013-05-15

Yanyanku and Ikpiru made by the fermentation of Malcavene bean (Hibiscus sabdariffa) are used as functional additives for Parkia biglobosa seed fermentations in Benin. A total of 355 aerobic endospore-forming bacteria (AEFB) isolated from Yanyanku and Ikpiru produced in northern and southern Benin were identified using phenotypic and genotypic methods, including GTG5-PCR, M13-PCR, 16S rRNA, gyrA and gyrB gene sequencing. Generally, the same 5-6 species of the genus Bacillus predominated: Bacillus subtilis (17-41% of isolates), Bacillus cereus (8-39%), Bacillus amyloliquefaciens (9-22%), Bacillus licheniformis (3-26%), Bacillus safensis (8-19%) and Bacillus altitudinis (0-19%). Bacillus aryabhattai, Bacillus flexus, and Bacillus circulans (0-2%), and species of the genera Lysinibacillus (0-14%), Paenibacillus (0-13%), Brevibacillus (0-4%), and Aneurinibacillus (0-3%) occurred sporadically. The diarrheal toxin encoding genes cytK-1, cytK-2, hblA, hblC, and hblD were present in 0%, 91% 15%, 34% and 35% of B. cereus isolates, respectively. 9% of them harbored the emetic toxin genetic determinant, cesB. This study is the first to identify the AEFB of Yanyanku and Ikpiru to species level and perform a safety evaluation based on toxin gene detections. We further suggest, that the gyrA gene can be used for differentiating the closely related species Bacillus pumilus and B. safensis. Copyright © 2013 Elsevier B.V. All rights reserved.

Conducting polymer based DNA biosensor for the detection of the Bacillus cereus group species

NASA Astrophysics Data System (ADS)

Velusamy, Vijayalakshmi; Arshak, Khalil; Korostynska, Olga; Oliwa, Kamila; Adley, Catherine

2009-05-01

Biosensor designs are emerging at a significant rate and play an increasingly important role in foodborne pathogen detection. Conducting polymers are excellent tools for the fabrication of biosensors and polypyrrole has been used in the detection of biomolecules due to its unique properties. The prime intention of this paper was to pioneer the design and fabrication of a single-strand (ss) DNA biosensor for the detection of the Bacillus cereus (B.cereus) group species. Growth of B. cereus, results in production of several highly active toxins. Therefore, consumption of food containing >106 bacteria/gm may results in emetic and diarrhoeal syndromes. The most common source of this bacterium is found in liquid food products, milk powder, mixed food products and is of particular concern in the baby formula industry. The electrochemical deposition technique, such as cyclic voltammetry, was used to develop and test a model DNA-based biosensor on a gold electrode electropolymerized with polypyrrole. The electrically conducting polymer, polypyrrole is used as a platform for immobilizing DNA (1μg) on the gold electrode surface, since it can be more easily deposited from neutral pH aqueous solutions of pyrrolemonomers. The average current peak during the electrodeposition event is 288μA. There is a clear change in the current after hybridization of the complementary oligonucleotide (6.35μA) and for the noncomplementary oligonucleotide (5.77μA). The drop in current after each event was clearly noticeable and it proved to be effective.

An ethnobotanical survey of mosquito repellent plants in uMkhanyakude district, KwaZulu-Natal province, South Africa.

PubMed

Mavundza, E J; Maharaj, R; Finnie, J F; Kabera, G; Van Staden, J

2011-10-11

The aim of the study was to document plants traditionally used to repel mosquitoes in the uMkhanyakude district, KwaZulu-Natal, South Africa. The specific objectives of the study were to: (1) identify plant species and their parts being used; (2) determine the condition of plant material used and the method of application. Data was collected from 60 respondents in five villages in the district using standardised and pre-tested questionnaires. Thirteen plant species are used in the study area to repel mosquitoes. These species belong to 11 genera from 9 families. Meliaceae and Anacardiaceae were the most represented families with two species each. The most frequently recorded species were Lippia javanica (91.67%), followed by Aloe ferox (11.67%), Sclerocarya birrea (5%), Melia azedarach (3%), Balanite maughamii (3%) and Mangifera indica (3%). Leaves were the most (38%) common plant part used. The majority (82%) of the plant parts were used in a dry state. Burning of plant materials to make smoke was the most (92%) common method of application. Nine plant species, namely: A. ferox, Calausena anista, Croton menyharthii, S. birrea, B. maughamii, Olax dissitiflora, Trichilia emetic, M. indica, and Atalaya alata are documented for the first time as mosquito repellents. This documentation provides the basis for further studies in developing new, effective, safe and affordable plant-derived mosquito repellents especially for Africa where malaria is highly prevalent. The study also plays a part in documenting and conserving traditional knowledge of mosquito repellent plants for future use. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Ondansetron rapidly dissolving film for the prophylactic treatment of radiation-induced nausea and vomiting-a pilot study.

PubMed

Wong, E; Pulenzas, N; Bedard, G; DeAngelis, C; Zhang, L; Tsao, M; Danjoux, C; Thavarajah, N; Lechner, B; McDonald, R; Cheon, P M; Chow, E

2015-06-01

The purpose of the present study was to investigate the efficacy of an ondansetron rapidly dissolving film (rdf) in the prophylaxis of radiation-induced nausea and vomiting (rinv). Rapidly dissolving film formulations facilitate drug delivery in circumstances in which swallowing the medication might be difficult for the patient. Patients undergoing palliative radiotherapy at risk for rinv were prescribed ondansetron rdf 8 mg twice daily while on treatment and were asked to complete a nausea and vomiting-specific daily diary, the Functional Living Index-Emesis (flie), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C15 Palliative (qlq-C15-pal). Patients were categorized as receiving primary or secondary prophylaxis based on whether they had already experienced emetic episodes. "Overall control" was defined as a maximum increase of 2 episodes of nausea or vomiting from baseline. "Acute phase" was defined as the days during radiation until the first day after radiation; "delayed phase" was defined as days 2-10 after radiation. The study accrued 30 patients. Rates of overall control for nausea and for vomiting during the acute phase in the primary prophylaxis group were 88% and 93% respectively; during the delayed phase, they were 73% and 75%. Rates of overall control for nausea and for vomiting during the acute phase in the secondary prophylaxis group were both 100%; during the delayed phase, they were 50%. The number of nausea and vomiting episodes was found to be significantly correlated with the flie and qlq-C15-pal questionnaires. Ondansetron rdf is effective for the prophylaxis of rinv.

Characterization of the use of antiemetic agents in dogs with parvoviral enteritis treated at a veterinary teaching hospital: 77 cases (1997-2000).

PubMed

Mantione, Nina L; Otto, Cynthia M

2005-12-01

To characterize the use of antiemetic agents in dogs with canine parvovirus (CPV)-associated enteritis in a veterinary teaching hospital. Retrospective case series. 77 dogs with CPV-associated enteritis. Medical records of 560 dogs with confirmed CPV-associated enteritis that were admitted to a veterinary teaching hospital were reviewed. Exclusion criteria included vaccination against CPV infection within the preceding 2 weeks, hospitalization for < 24 hours or removal from the hospital against advice, or an incomplete record. Signalment, duration of hospitalization, and daily antiemetic administrations were assessed; WBC counts and clinical findings were used to classify dogs as having systemic inflammatory response syndrome (SIRS). 77 dogs were included in the study; 55 (71%) received antiemetics (53 received metoclopramide at least once). Seventy-one dogs survived, and 6 dogs died (all 6 received antiemetics). Compared with dogs that did not receive antiemetics, duration of hospitalization was significantly longer for antiemetic-treated dogs. Daily values of rectal temperature and heart and respiratory rates did not predict administration of antiemetics or duration of hospitalization; however, compared with survivors, SIRS developed more frequently among nonsurvivors. Assessment of emetic events recorded hourly for 17 dogs indicated that antiemetic treatment did not control emesis. Many dogs with CPV-associated enteritis had persistent vomiting despite antiemetic administration. The apparent difference in duration of hospitalization between antiemetic-treated dogs and other dogs may reflect a difference in disease severity between groups, although antiemetic-associated adverse events (e.g., signs of depression, hypotension, and immune modulation) may prolong hospitalization.

RF photo-injector beam energy distribution studies by slicing technique

NASA Astrophysics Data System (ADS)

Filippetto, D.; Bellaveglia, M.; Musumeci, P.; Ronsivalle, C.

2009-07-01

The SPARC photo-injector is an R&D facility dedicated to the production of high brightness electron beams for radiation generation via FEL or Thomson scattering processes. It is the prototype injector for the recently approved SPARX project, aiming at the construction in the Frascati/University of Rome Tor Vergata area of a new high brightness electron linac for the generation of SASE-FEL radiation in the 1-10 nm wavelength range. The first phase of the SPARC project has been dedicated to the e-beam source characterization; the beam transverse and longitudinal parameters at the exit of the gun have been measured, and the photo-injector settings optimized to achieve best performance. Several beam dynamics topics have been experimentally studied in this first phase of operation, as, for example, the effect of photocathode driver laser beam shaping and the evolution of the beam transverse emittance. These studies have been made possible by the use of a novel diagnostic tool, the " emittance-meter" which enables the measurement of the transverse beam parameters at different positions along the propagation axis in the very interesting region at the exit of the RF gun. The new idea of extending the e-meter capabilities came out more recently. Information on the beam longitudinal phase space and correlations with the transverse planes can be retrieved by the slicing technique. In this paper, we illustrate the basic concept of the measurement together with simulations that theoretically validate the methodology. Some preliminary results are discussed and explained with the aid of code simulations.

A randomized, double-blinded comparison of ondansetron, granisetron, and placebo for prevention of postoperative nausea and vomiting after supratentorial craniotomy.

PubMed

Jain, Virendra; Mitra, Jayanta K; Rath, Girija P; Prabhakar, Hemanshu; Bithal, Parmod K; Dash, Hari H

2009-07-01

Postoperative nausea and vomiting (PONV) are frequent and distressing complications after neurosurgical procedures. We evaluated the efficacy of ondansetron and granisetron to prevent PONV after supratentorial craniotomy. In a randomized double-blind, placebo controlled trial, 90 adult American Society of Anesthesiologists I, II patients were included in the study. A standard anesthesia technique was followed. Patients were divided into 3 groups to receive either placebo (saline), ondansetron 4 mg, or granisetron 1 mg intravenously at the time of dural closure. After extubation, episodes of nausea and vomiting were noted for 24 hours postoperatively. Statistical analysis was performed using chi2 test and 1-way analysis of variance. Demographic data, duration of surgery, intraoperative fluids and analgesic requirement, and postoperative pain (visual analog scale) scores were comparable in all 3 groups. It was observed that the incidence of vomiting in 24 hours, severe emetic episodes, and requirement of rescue antiemetics were less in ondansetron and granisetron groups as compared with placebo (P<0.001). Both the study drugs had comparable effect on vomiting. However, the incidence of nausea was comparable in all 3 groups (P=0.46). A favorable influence on the patient satisfaction scores, and number needed to prevent emesis was seen in the 2 drug groups. No significant correlation was found between neurosurgical factors (presence of midline shift, mass effect, pathologic diagnosis of tumor, site of tumor) and the occurrence of PONV. We conclude that ondansetron 4 mg and granisetron 1 mg are comparably effective at preventing emesis after supratentorial craniotomy. However, neither drugs prevented nausea effectively.

Ramosetron compared with granisetron for the prevention of vomiting following strabismus surgery in children

PubMed Central

Fujii, Y.; Tanaka, H.; Ito, M.

2001-01-01

BACKGROUND/AIMS—Postoperative vomiting occurs frequently after strabismus surgery in children. Granisetron, a selective 5-hydroxytryptamine type 3 receptor antagonist, is effective for the prevention of vomiting following paediatric strabismus surgery. Ramosetron, another new antagonist of 5-hydroxytryptamine type 3 receptor, has more potent and longer acting properties than granisetron against cisplatin induced emesis. This study was undertaken to compare the efficacy and safety of granisetron and ramosetron for the prevention of vomiting following strabismus surgery in children.
METHODS—In a randomised, double blinded manner 80 children, aged 4-10 years, received intravenously granisetron 40 µg/kg or ramosetron 6 µg/kg (n=40 each) at the end of surgery. A standard general anaesthetic technique and postoperative analgesia were used. Emetic episodes and safety assessment were performed during the first 24 hours and the next 24 hours after anaesthesia.
RESULTS—The percentage of patients who were emesis free during 0-24 hours after anaesthesia was 85% with granisetron and 90% with ramosetron, respectively (p = 0.369); the corresponding rate during 24-48 hours after anaesthesia was 70% and 95% (p = 0.003). No clinically serious adverse events caused by the study drug were observed in any of the groups.
CONCLUSION—Prophylactic antiemetic therapy with ramosetron is comparable with granisetron for the prevention of vomiting during 0-24 hours after anaesthesia in children undergoing strabismus surgery. During 24-48 hours after anaesthesia, ramosetron is more effective than granisetron for prophylaxis against postoperative vomiting.

 PMID:11371485

Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study

PubMed Central

Kimura, Hiroaki; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hideji; Hayashi, Katsuhiro; Tanzawa, Yoshikazu; Takeuchi, Akihiko; Igarashi, Kentaro; Inatani, Hiroyuki; Shimozaki, Shingo; Kato, Takashi; Aoki, Yu; Higuchi, Takashi; Tsuchiya, Hiroyuki

2015-01-01

The first aim of this study was to evaluate combination antiemetic therapy consisting of 5-HT3 receptor antagonists, neurokinin-1 receptor antagonists (NK-1RAs), and dexamethasone for multiple high emetogenic risk (HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting (CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV. PMID:25533447

Iridoids as chemical markers of false ipecac (Ronabea emetica), a previously confused medicinal plant.

PubMed

Berger, Andreas; Fasshuber, Hannes; Schinnerl, Johann; Robien, Wolfgang; Brecker, Lothar; Valant-Vetschera, Karin

2011-12-08

Several roots or rhizomes of rubiaceous species are reportedly used as the emetic and antiamoebic drug ipecac. True ipecac (Carapichea ipecacuanha) is chemically well characterized, in contrast to striated or false ipecac derived from the rhizomes of Ronabea emetica (syn. Psychotria emetica). Besides its previous use as substitute of ipecac, the latter species is applied in traditional medicine of Panama and fruits of its relative Ronabea latifolia are reported as curare additives from Colombia. Compounds of Ronabea emetica were isolated using standard chromatographic techniques, and structurally characterized by NMR spectroscopy and mass spectrometry. Organ specific distribution in Ronabea emetica as well as in Ronabea latifolia was further assessed by comparative HPLC analysis. Four iridoid-glucosides, asperuloside (1), 6α-hydroxygeniposide (2), deacetylasperulosidic acid (3) and asperulosidic acid (4) were extracted from leaves of Ronabea emetica. Rhizomes, used in traditional medicine, were dominated by 3. HPLC profiles of Ronabea latifolia were largely corresponding. These results contrast to the general tendency of producing emetine-type and indole alkaloids in species of Psychotria and closely related genera and merit chemotaxonomic significance, characterizing the newly delimited genus Ronabea. The aim of the work was to resolve the historic problem of adulteration of ipecac by establishing the chemical profile of Ronabea emetica, the false ipecac, as one of its less known sources. The paper demonstrates that different sources of ipecac can be distinguished by their phytochemistry, thus contributing to identifying adulterations of true ipecac. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Comparison of treatment patterns and economic outcomes among metastatic pancreatic cancer patients initiated on nab-paclitaxel plus gemcitabine versus FOLFIRINOX.

PubMed

McBride, Ali; Bonafede, Machaon; Cai, Qian; Princic, Nicole; Tran, Oth; Pelletier, Corey; Parisi, Monika; Patel, Manish

2017-10-01

The economic burden of metastatic pancreatic cancer (mPC) is substantial while treatment options are limited. Little is known about the treatment patterns and healthcare costs among mPC patients who initiated first-line gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-P + G) and FOLFIRINOX. The MarketScan® claims databases were used to identify adults with ≥2 claims for pancreatic cancer, 1 claim for a secondary malignancy, completed ≥1 cycle of nab-P + G or FOLFIRINOX during 4/1/2013 and 3/31/2015, and had continuous plan enrollment for ≥6 months pre- and 3 months after the first-line treatment. Duration of therapy, per patient per month (PPPM) costs of total healthcare, mPC-related treatment, and supportive care were measured during first-line therapy. 550 mPC patients met selection criteria (nab-P + G, n = 294; FOLFIRINOX, n = 256). There was no difference in duration of therapy (p = 0.60) between nab-P + G and FOLFIRINOX. Compared with FOLFIRINOX, patients with nab-P + G had higher chemotherapy drug costs but lower treatment administration costs and supportive care costs (all p < 0.01). Patients treated with nab-P + G (vs FOLFIRINOX) had similar treatment duration but lower costs of outpatient prescriptions, treatment administration and supportive care. Lower supportive care costs in the nab-P + G cohort were mainly driven by lower utilization of pegfilgrastim and anti-emetics.

Cold pearl surfactant-based blends.

PubMed

Crombie, R L

1997-10-01

Pearlizing agents have been used for many years in cosmetic formulations to add a pearlescent effect. Cold pearl surfactant-based blends are mixtures of glycol stearates and surfactants which can be blended in the cold into a wide range of personal-care formulations to create a pearlescent lustre effect. Under controlled manufacturing conditions constant viscosities and crystalline characteristics can be obtained. The development of these blends has been driven by efforts to improve the economics of adding solid pearlizing agents directly into a hot mix formulation. This paper summarizes the history of pearlizers, describes their advantages and physical chemistry of the manufacturing process. Finally some suggestions for applications are given. Les agents nacrants sont utilises depuis de nombreuses annees dans les formulations cosmetiques pour ajouter un effet nacre. Les melanges a froid a base de tensioactif nacre sont des melanges de stearates de glycol et de tensioactifs qui peuvent etre melanges a froid dans une large gamme de formulations d'hygiene personnelle pour creer un effet de lustre nacre. On peut obtenir des viscosites et des proprietes cristallines constantes avec des conditions de fabrication maitrisees. Le developpement de ces melanges a ete porte par les efforts pour ameliorer les couts de l'ajout d'agents nacrants solides directement dans une formulation melangee de l'ajout d'agents nacrants solides directement dans une formulation melangee a chaud. Cet article resume l'histoire des agents nacrants, decrit leurs avantages et al physico-chimie du procede de fabrication. On emet a la fin cetaines suggestions d'applications.

Pharmaceutical services in a Mexican pain relief and palliative care institute

PubMed Central

Escutia Gutiérrez, Raymundo; Cortéz Álvarez, César R.; Álvarez Álvarez, Rosa M.; Flores Hernández, Jorge LV.; Gutiérrez Godínez, Jéssica; López Y López, José G.

Neither the purchase nor the distribution of pharmaceuticals in hospitals and community pharmacies in Mexico is under the care of pharmacists. Some are under control of physicians. This report presents the results of the implementation of somef pharmaceutical services for the Jalisco Pain Relief, and Palliative Care Institute (Palia Institute), under the direction of the Secretary of Health, Government of Jalisco. The services implemented were drug distribution system, Drug Information Service, Pharmacovigilance Program, and home pharmacotherapy follow-up pilot program for patients with advanced illness, with the ultimate using the appropriate medication. The drug distribution system included dispensing of opioid pain medications, antidepressants, anticonvulsants, NSAIDs, anxiolytic drugs, steroid drugs, laxatives, and anti-emetics. The frequently used drugs were morphine sulfate (62%), amitriptyline (6.4%), and dextropropoxyphene (5.8%). The Drug Information Service answered 114 consultations, mainly asked by a physician (71%) concerned with adverse drug reactions and contraindications (21%). The pharmacovigilance program identified 146 suspected adverse drug reactions and classified them reasonably as possible (27%), probable (69%), and certain (4%). These were attributed mainly to pregabalin and tramadol. The home pharmacotherapy follow-up pilot program cared patients with different cancer diagnoses and drug-related problems (DRP), which were identified and classified (according to second Granada Consensus) for pharmaceutical intervention as DRP 1 (5%), DRP 2 (10%), DRP 3 (14%), DRP 4 (19%), DRP 5 (24%), or DRP 6 (28%). This report provides information concerning the accurate use of medication and, above all, an opportunity for Mexican pharmacists to become an part of health teams seeking to resolve drug-related problems. PMID:25170355

Volatile secondary metabolites as aposematic olfactory signals and defensive weapons in aquatic environments

PubMed Central

Giordano, Giuseppe; Carbone, Marianna; Ciavatta, Maria Letizia; Silvano, Eleonora; Gavagnin, Margherita; Garson, Mary J.; Cheney, Karen L.; Mudianta, I Wayan; Russo, Giovanni Fulvio; Villani, Guido; Magliozzi, Laura; Zidorn, Christian; Cutignano, Adele; Fontana, Angelo; Ghiselin, Michael T.

2017-01-01

Olfaction is considered a distance sense; hence, aquatic olfaction is thought to be mediated only by molecules dissolved in water. Here, we challenge this view by showing that shrimp and fish can recognize the presence of hydrophobic olfactory cues by a “tactile” form of chemoreception. We found that odiferous furanosesquiterpenes protect both the Mediterranean octocoral Maasella edwardsi and its specialist predator, the nudibranch gastropod Tritonia striata, from potential predators. Food treated with the terpenes elicited avoidance responses in the cooccurring shrimp Palaemon elegans. Rejection was also induced in the shrimp by the memory recall of postingestive aversive effects (vomiting), evoked by repeatedly touching the food with chemosensory mouthparts. Consistent with their emetic properties once ingested, the compounds were highly toxic to brine shrimp. Further experiments on the zebrafish showed that this vertebrate aquatic model also avoids food treated with one of the terpenes, after having experienced gastrointestinal malaise. The fish refused the food after repeatedly touching it with their mouths. The compounds studied thus act simultaneously as (i) toxins, (ii) avoidance-learning inducers, and (iii) aposematic odorant cues. Although they produce a characteristic smell when exposed to air, the compounds are detected by direct contact with the emitter in aquatic environments and are perceived at high doses that are not compatible with their transport in water. The mouthparts of both the shrimp and the fish have thus been shown to act as “aquatic noses,” supporting a substantial revision of the current definition of the chemical senses based upon spatial criteria. PMID:28289233

Neuropathology of the area postrema in sudden intrauterine and infant death syndromes related to tobacco smoke exposure.

PubMed

Lavezzi, Anna Maria; Mecchia, Donatella; Matturri, Luigi

2012-01-26

The area postrema is a densely vascularized small protuberance at the inferoposterior limit of the fourth ventricle, outside of the blood-brain barrier. This structure, besides to induce emetic reflex in the presence of noxious chemical stimulation, has a multifunctional integrative capacity to send major and minor efferents to a variety of brain centers particularly involved in autonomic control of the cardiovascular and respiratory activities. In this study we aimed to focus on the area postrema, which is so far little studied in humans, in a large sample of subjects aged from 25 gestational weeks to 10 postnatal months, who died of unknown (sudden unexplained perinatal and infant deaths) and known causes (controls). Besides we investigated a possible link between alterations of this structure, sudden unexplained fetal and infant deaths and maternal smoking. By the application of morphological and immunohistochemical methods, we observed a significantly high incidence of alterations of the area postrema in fetal and infant victims of sudden death as compared with age-matched controls. These pathological findings, including hypoplasia, lack of vascularization, cystic formations and reactive gliosis, were related to maternal smoking. We hypothesize that components from maternal cigarette smoke, particularly in pregnancy, could affect neurons of the area postrema connected with specific nervous centers involved in the control of vital functions. In conclusion, we suggest that the area postrema should be in depth examined particularly in victims of sudden fetal or infant death with smoker mothers. Copyright © 2011 Elsevier B.V. All rights reserved.

Postoperative analgesia and antiemetic efficacy after intrathecal neostigmine in patients undergoing abdominal hysterectomy during spinal anesthesia.

PubMed

Lauretti, G R; Mattos, A L; Gomes, J M; Pereira, N L

1997-01-01

Postoperative analgesia and antiemetic efficacy after intrathecal neostigmine were investigated in a randomized, double-blind, placebo-controlled trial of 100 patients undergoing abdominal hysterectomy. The patients were assigned to one of five groups (n = 20), and received intravenous prior to the spinal block the antiemetic test drug (except propofol) and 0.05 mg/kg midazolam. The control group (group C), the neostigmine group (group N), and the propofol group (group P) received saline as the test drug. The droperidol group (group D) received 0.5 mg intravenous droperidol, and the metoclopramide group (group M) 10 mg intravenous metoclopramide. Group P was single-blinded and had an intravenous continuous propofol infusion (2-4 mg/kg/h) turned on 10 minutes after the spinal injection. The intrathecal drugs administered were 20 mg hyperbaric bupivacaine (0.5%) associated with either 100 microg neostigmine or saline (for group C). Nausea, emetic episodes, and the need for rescue medication were recorded for the first 24 hours postoperative and scored by the Visual Analog Scale (VAS). Time-to-first-rescue medication and rescue medications in 24 hours were similar among the groups (P = .2917 and P = .8780, respectively). Intrathecal 100 microg neostigmine was associated with a high incidence of nausea and vomiting perioperative, leading to a high consumption of antiemetics (P < .002). None of the antiemetic test drugs were effective in preventing nausea and vomiting after 100 microg neostigmine. Intrathecal neostigmine (100 microg) was ineffective for postoperative analgesia after abdominal hysterectomy due to side effects of nausea and vomiting.

Fabrication of an electrochemical DNA-based biosensor for Bacillus cereus detection in milk and infant formula.

PubMed

Izadi, Zahra; Sheikh-Zeinoddin, Mahmoud; Ensafi, Ali A; Soleimanian-Zad, Sabihe

2016-06-15

This paper describes fabrication of a DNA-based Au-nanoparticle modified pencil graphite electrode (PGE) biosensor for detection of Bacillus cereus, causative agent of two types of food-borne disease, i.e., emetic and diarrheal syndrome. The sensing element of the biosensor was comprised of gold nanoparticles (GNPs) self-assembled with single-stranded DNA (ssDNA) of nheA gene immobilized with thiol linker on the GNPs modified PGE. The size, shape and dispersion of the GNPs were characterized by field emission scanning electron microscope (FESEM). Detection of B. cereus was carried out based on an increase in the charge transfer resistance (Rct) of the biosensor due to hybridization of the ss-DNA with target DNA. An Atomic force microscope (AFM) was used to confirm the hybridization. The biosensor sensitivity in pure cultures of B. cereus was found to be 10(0) colony forming units per milliliter (CFU/mL) with a detection limit of 9.4 × 10(-12) mol L(-1). The biosensor could distinguish complementary from mismatch DNA sequence. The proposed biosensor exhibited a rapid detection, low cost, high sensitivity to bacterial contamination and could exclusively and specifically detect the target DNA sequence of B. cereus from other bacteria that can be found in dairy products. Moreover, the DNA biosensor exhibited high reproducibility and stability, thus it may be used as a suitable biosensor to detect B. cereus and to become a portable system for food quality control. Copyright © 2016 Elsevier B.V. All rights reserved.

A targetted intervention research on traditional healer perspectives of sexually transmitted illnesses in urban Zambia. Current research.

PubMed

Masauso Nzima, M; Romano, K; Anyangwe, S; Wiseman, J; Macwan'gi, M; Kendall, C; Green, E C

1996-07-01

Interviews with 81 traditional healers from 4 Copperbelt towns in Zambia (Chililabombwe, Chingola, Luanshya, and Mufulira) investigated healers' understanding of, attitudes toward, and management of sexually transmitted diseases (STDs). In general, Zambian traditional healers had detailed constructs of the physiology and infective processes underlying syphilis, gonorrhea, chancroid, and AIDS. STDs were considered to be caused by "dirt" or contamination residing in sperm or vaginal fluids and were closely linked to violations of moral codes. Healers shared complex nosologies based on distinctions between symptoms of different STD pathologies that were more inclusive than biomedical categories. Although condom use was not promoted, healers understood the importance of preventing an infective agent from passing from one person to another. Except for AIDS, STDs were considered curable by expelling the dirt through purgatives or emetics. Modern medicine was perceived as treating only STD symptoms, not curing. Most traditional healers insisted that the infected partner bring the other partner for consultation or treatment was withheld. Since these findings identified some areas of compatibility between indigenous and biomedical models of STDs, the Traditional Medicine Unit of the Ministry of Health and the HIV/AIDS Prevention Project of the Morehouse School of Medicine (Lusaka) established a program in which traditional healers receive AIDS training and learn to counsel clients on safer sex behaviors. Follow-up entails monthly meetings between health professionals and traditional healers. Since program initiation in June 1994, 800 traditional healers and 70 health professionals have participated. Traditional healers now sell condoms to their clients through a social marketing program.

Brainstem processing of vestibular sensory exafference: implications for motion sickness etiology

PubMed Central

Oman, Charles M.; Cullen, Kathleen E.

2014-01-01

The origin of the internal “sensory conflict” stimulus causing motion sickness has been debated for more than four decades. Recent studies show a subclass of neurons in the vestibular nuclei and deep cerebellar nuclei that respond preferentially to passive head movements. During active movement, the semicircular canal and otolith input (“reafference”) to these neurons is cancelled by a mechanism comparing the expected consequences of self-generated movement (estimated with an internal model-presumably located in the cerebellum) with the actual sensory feedback. The un-cancelled component (“exafference”) resulting from passive movement normally helps compensate for unexpected postural disturbances. Notably, the existence of such vestibular “sensory conflict” neurons had been postulated as early as 1982, but their existence and putative role in posture control, motion sickness has been long debated. Here we review the development of “sensory conflict” theories in relation to recent evidence for brainstem and cerebellar reafference cancellation, and identify some open research questions. We propose that conditions producing persistent activity of these neurons, or their targets, stimulates nearby brainstem emetic centers – via an as yet unidentified mechanism. We discuss how such a mechanism is consistent with the notable difference in motion sickness susceptibility of drivers as opposed to passengers, human immunity to normal self-generated movement, and why head restraint or lying horizontal confers relative immunity. Finally, we propose that fuller characterization of these mechanisms, and their potential role in motion sickness could lead to more effective, scientifically based prevention and treatment for motion sickness. PMID:24838552

Contrasting Effects of Lithium Chloride and CB1 Receptor Blockade on Enduring Changes in the Valuation of Reward.

PubMed

Hernandez, Giovanni; Bernstein, David; Schoenbaum, Geoffrey; Cheer, Joseph F

2011-01-01

When an organism responds for a reward, its learned behavior can be characterized as goal-directed or habitual based on whether or not it is susceptible to reward devaluation. Here, we evaluated whether instrumental responding for brain stimulation reward (BSR) can be devalued using a paradigm traditionally used for natural rewards. Rats were trained to lever press for BSR; afterward, BSR was paired with either lithium chloride (LiCl, 5 mg/kg, i.p.), a pro-emetic, or AM251, a CB1 receptor antagonist (3 mg/kg, i.p.) or the vehicle of these compounds. Pairings of BSR with these compounds and their vehicles were performed in a novel environment so that only unconditional effects of BSR would be affected by the pharmacological manipulations. Subsequently, in a probe test, all rats were returned in the drug-free state to the boxes where they had received training and instrumental responding was reassessed in the absence of BSR delivery. When compared to control, LiCl produced a significant decrease in the number of responses during the test session, whereas AM251 did not. These results show that instrumental responding for BSR is susceptible to devaluation, in accord with the proposal that this behavior is supported at least in part by associations between the response and the rewarding outcome. Further, they suggest that reward modulation observed in studies involving the use of CB1 receptor antagonists arises from changes in the organism's motivation rather than drug-induced changes in the intrinsic value of reward.

The value of integrating pre-clinical data to predict nausea and vomiting risk in humans as illustrated by AZD3514, a novel androgen receptor modulator.

PubMed

Grant, Claire; Ewart, Lorna; Muthas, Daniel; Deavall, Damian; Smith, Simon A; Clack, Glen; Newham, Pete

2016-04-01

Nausea and vomiting are components of a complex mechanism that signals food avoidance and protection of the body against the absorption of ingested toxins. This response can also be triggered by pharmaceuticals. Predicting clinical nausea and vomiting liability for pharmaceutical agents based on pre-clinical data can be problematic as no single animal model is a universal predictor. Moreover, efforts to improve models are hampered by the lack of translational animal and human data in the public domain. AZD3514 is a novel, orally-administered compound that inhibits androgen receptor signaling and down-regulates androgen receptor expression. Here we have explored the utility of integrating data from several pre-clinical models to predict nausea and vomiting in the clinic. Single and repeat doses of AZD3514 resulted in emesis, salivation and gastrointestinal disturbances in the dog, and inhibited gastric emptying in rats after a single dose. AZD3514, at clinically relevant exposures, induced dose-responsive "pica" behaviour in rats after single and multiple daily doses, and induced retching and vomiting behaviour in ferrets after a single dose. We compare these data with the clinical manifestation of nausea and vomiting encountered in patients with castration-resistant prostate cancer receiving AZD3514. Our data reveal a striking relationship between the pre-clinical observations described and the experience of nausea and vomiting in the clinic. In conclusion, the emetic nature of AZD3514 was predicted across a range of pre-clinical models, and the approach presented provides a valuable framework for predicition of clinical nausea and vomiting. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparative efficacy of maropitant and selected drugs in preventing emesis induced by centrally or peripherally acting emetogens in dogs.

PubMed

Sedlacek, H S; Ramsey, D S; Boucher, J F; Eagleson, J S; Conder, G A; Clemence, R G

2008-12-01

Maropitant (Cerenia; a novel, selective neurokinin(1) receptor antagonist), chlorpromazine, metoclopramide and ondansetron were compared in two randomized, placebo-controlled studies for efficacy in preventing emesis induced by emetogens acting centrally (apomorphine; Study 1) or peripherally (syrup of ipecac; Study 2) in dogs. In each study, ten male and ten female beagles were treated in a five-treatment, five-period crossover design. The five treatments were 0.9% saline (0.1 mL/kg), maropitant (1 mg/kg), metoclopramide (0.5 mg/kg), or chlorpromazine (0.5 mg/kg) all administered subcutaneously, or ondansetron (0.5 mg/kg) administered intravenously. One hour posttreatment dogs were challenged with apomorphine at 0.1 mg/kg intravenously (Study 1) or syrup of ipecac at 0.5 mL/kg orally (Study 2). Following emetogen challenge, dogs were observed for 30 min (Study 1) or 1 h (Study 2) for emesis. No clinical signs, other than those related to emesis, were observed. Efficacy of maropitant in preventing emesis induced centrally by apomorphine was not different (P > 0.05) from metoclopramide or chlorpromazine but was superior (P < 0.0001) to ondansetron. Efficacy of maropitant in preventing emesis induced by syrup of ipecac was not different (P > 0.05) from ondansetron but was superior (P emetic pathways, whereas the other drugs examined prevented vomiting caused by central (metoclopramide and chlorpromazine; P < 0.0001) or peripheral (ondansetron; P < 0.0001) stimulation but not both.

Co-administration of dexamethasone increases severity and accelerates onset day of neutropenia in bladder cancer patients on methotrexate, vinblastine, adriamycin and cisplatin chemotherapy: a retrospective cohort study.

PubMed

Itai, Shingo; Suga, Yukio; Hara, Yusuke; Izumi, Kouji; Maeda, Yuji; Kitagawa, Yasuhide; Ishizaki, Junko; Shimada, Tsutomu; Mizokami, Atsushi; Sai, Yoshimichi

2017-01-01

Bladder cancer patients receiving methotrexate, vinblastine, adriamycin and cisplatin (MVAC) chemotherapy are co-administered with dexamethasone as an anti-emetic. We examined whether or not dexamethasone affects the severity and onset day of MVAC-induced severe neutropenia. This was a retrospective study of bladder cancer patients treated with MVAC chemotherapy with or without dexamethasone as an antiemetic at Kanazawa University Hospital during January 2005 - December 2009. Patients were categorized into three groups; no dexamethasone use (Dex (-)), dexamethasone on day 2 (Dex 1 day), and dexamethasone on days 2, 3 and 4 (Dex multiday). We evaluated the incidence of grade 3/4 neutropenia and the day of onset of first severe neutropenic episode during the first course of MVAC chemotherapy. Logistic regression was used to investigate whether co-administration of dexamethasone was a risk factor for severe neutropenia. Episodes of grade 3/4 neutropenia occurred in 3 out of 6 (50.0%), 11 out of 12 (91.7%) and 6 out of 6 (100%) patients in the Dex (-), Dex 1 day, and Dex multiday groups, respectively. The appearance day of first severe neutropenia in the Dex multiday group (13.2 ± 1.0) was significantly accelerated compared to the Dex (-) group (17.7 ± 2.1). Univariate logistic regression analysis revealed that dexamethasone is a risk factor for severe neutropenia (OR 17.0; 95%CI: 1.3-223.1). Co-administration of dexamethasone for anti-emesis brings forward the first appearance of neutropenia, and increases the severity of neutropenia, in bladder cancer patients receiving MVAC chemotherapy.

Efficacy and safety of acupuncture for dizziness and vertigo in emergency department: a pilot cohort study.

PubMed

Chiu, Chih-Wen; Lee, Tsung-Chieh; Hsu, Po-Chi; Chen, Chia-Yun; Chang, Shun-Chang; Chiang, John Y; Lo, Lun-Chien

2015-06-09

Dizziness and vertigo account for roughly 4% of chief symptoms in the emergency department (ED). Pharmacological therapy is often applied for these symptoms, such as vestibular suppressants, anti-emetics and benzodiazepines. However, every medication is accompanied with unavoidable side-effects. There are several research articles providing evidence of acupuncture treating dizziness and vertigo but few studies of acupuncture as an emergent intervention in ED. We performed a pilot cohort study to evaluate the efficacy and safety of acupuncture in treating patients with dizziness and vertigo in ED. A total of 60 participants, recruited in ED, were divided into acupuncture and control group. Life-threatening conditions or central nervous system disorders were excluded to ensure participants' safety. The clinical effect of treating dizziness and vertigo was evaluated by performing statistical analyses on data collected from questionnaires of Dizziness Handicap Inventory (DHI), Visual Analog Scale (VAS) of dizziness and vertigo, and heart rate variability (HRV). The variation of VAS demonstrated a significant decrease (p-value: 0.001 and p-value: 0.037) between two groups after two different durations: 30 mins and 7 days. The variation of DHI showed no significant difference after 7 days. HRV revealed a significant increase in high frequency (HF) in the acupuncture group. No adverse event was reported in this study. Acupuncture demonstrates a significant immediate effect in reducing discomforts and VAS of both dizziness and vertigo. This study provides clinical evidence on the efficacy and safety of acupuncture to treat dizziness and vertigo in the emergency department. ClinicalTrials.gov ID: NCT02358239 . Registered 5 February 2015.

Therapeutic potential of monoacylglycerol lipase inhibitors.

PubMed

Mulvihill, Melinda M; Nomura, Daniel K

2013-03-19

Marijuana and aspirin have been used for millennia to treat a wide range of maladies including pain and inflammation. Both cannabinoids, like marijuana, that exert anti-inflammatory action through stimulating cannabinoid receptors, and cyclooxygenase (COX) inhibitors, like aspirin, that suppress pro-inflammatory eicosanoid production have shown beneficial outcomes in mouse models of neurodegenerative diseases and cancer. Both cannabinoids and COX inhibitors, however, have untoward effects that discourage their chronic usage, including cognitive deficits and gastrointestinal toxicity, respectively. Recent studies have uncovered that the serine hydrolase monoacylglycerol lipase (MAGL) links the endocannabinoid and eicosanoid systems together through hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG) to provide the major arachidonic acid (AA) precursor pools for pro-inflammatory eicosanoid synthesis in specific tissues. Studies in recent years have shown that MAGL inhibitors elicit anti-nociceptive, anxiolytic, and anti-emetic responses and attenuate precipitated withdrawal symptoms in addiction paradigms through enhancing endocannabinoid signaling. MAGL inhibitors have also been shown to exert anti-inflammatory action in the brain and protect against neurodegeneration through lowering eicosanoid production. In cancer, MAGL inhibitors have been shown to have anti-cancer properties not only through modulating the endocannabinoid-eicosanoid network, but also by controlling fatty acid release for the synthesis of protumorigenic signaling lipids. Thus, MAGL serves as a critical node in simultaneously coordinating multiple lipid signaling pathways in both physiological and disease contexts. This review will discuss the diverse (patho)physiological roles of MAGL and the therapeutic potential of MAGL inhibitors in treating a vast array of complex human diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

Systemic lupus erythematosus pancreatitis: an uncommon presentation of a common disease.

PubMed

Rodriguez, Eduardo A; Sussman, Daniel A; Rodriguez, Vanessa R

2014-11-17

Acute pancreatitis is uncommon in systemic lupus erythematosus (SLE). When recognized early and properly treated with IV steroids and hydration, the course may be benign, as exemplified in the following report. A 21-year-old woman with history of SLE and stage IV lupus nephritis, was admitted to the Sergio Bernales Hospital ICU (Lima, Peru), complaining of worsening epigastric pain radiating to the back, and nausea and vomiting for 1 week. She denied prior cholelithiasis, alcohol use, or recent medication changes. On examination, she was tachycardic and normotensive, with a slightly distended abdomen and epigastric tenderness on deep palpation, without signs of peritoneal irritation. Laboratory results demonstrated leukocytosis without left shift, creatinine of 2.26 mg/dL, amylase of 750 U/L, and lipase of 1038 U/L. Liver chemistries, calcium, lactic acid, triglycerides, and IgG4 were normal and alcohol level was undetectable. Ultrasound did not show cholelithiasis, biliary sludge, or common bile duct dilation. CT of the abdomen showed pancreas head (parenchyma) stranding with uniform enhancement consistent with interstitial pancreatitis. Despite receiving IV fluids, opiates, anti-emetics, and nothing by mouth, her clinical condition deteriorated, prompting the use of IV methylprednisolone. After completing 1 week of IV steroids, she was transferred to the medical floor clinically improved. The patient was discharged with an oral steroid taper and complete resolution of symptoms. After ruling out common causes, such as hepatobiliary pathology or toxin-related insults like alcohol, hypercalcemia, hypertriglyceridemia or medications, steroids may be used in SLE pancreatitis because they might improve the overall prognosis.

Medicinal properties of Peganum harmala L. in traditional Iranian medicine and modern phytotherapy: a review.

PubMed

Mina, Cheraghi Niroumand; Farzaei, Mohammad Hosein; Gholamreza, Amin

2015-02-01

To review the pharmacological activities of Peganum harmala L. (P. harmala, Nitrariaceae) in traditional Iranian medicine (TIM) and modern phytotherapy. Opinions of TIM and modern phytotherapy about safety and acceptable dosage of this plant are discussed. Various medical properties of P. harmala were collected from important TIM references and added to scientific reports derived from modern medical databases like PubMed, Scirus, ScienceDirect and Scopus. The main medicinal part of the plant is the seed. In TIM resources, this plant possesses various Pharmacological activities such as carminative, galactagogue, diuretic, emmenagogue, antithrombotic and analgesic. In modern phytotherapy, P. harmala demonstrated numerous medicinal effects including cardiovascular, neurologic, antimicrobial, insecticidal, antineoplasmic, antiproliferative, gastrointestinal and antidiabetic effects. Adverse events such as neuro-sensorial symptoms, visual hallucination, bradycardia, hypotension, agitation, tremors, ataxia, abortion and vomiting cause people to use this plant cautiously. P. harmala is contraindicated during pregnancy, due to its abortive and mutagenic activities. Because of increasing the expression of CYP1A2, 2C19, and 3A4 and inhibition of monoamine oxidase, the pharmacokinetic parameters of drugs which are mainly metabolized by these enzymes may be affected by P. harmala. The medicinal properties declared for this plant in TIM are compared with those showed in modern phytotherapy. Some of the TIM properties were confirmed in modern phytotherapy like emetic and analgesic activities and some have not been evaluated in modern phytotherapy such as its therapeutic effects on paralysis, epilepsy and numbness. Finally, the current review provides the evidence for other researchers to use TIM properties of P. harmala as an efficacious natural drug. Further preclinical and clinical studies for adequate evaluating safety and therapeutic efficacy are recommended.

Oral hygiene products and acidic medicines.

PubMed

Hellwig, E; Lussi, A

2006-01-01

Acidic or EDTA-containing oral hygiene products and acidic medicines have the potential to soften dental hard tissues. The low pH of oral care products increases the chemical stability of some fluoride compounds, favors the incorporation of fluoride ions in the lattice of hydroxyapatite and the precipitation of calcium fluoride on the tooth surface. This layer has some protective effect against an erosive attack. However, when the pH is too low or when no fluoride is present these protecting effects are replaced by direct softening of the tooth surface. Xerostomia or oral dryness can occur as a consequence of medication such as tranquilizers, anti-histamines, anti-emetics and anti-parkinsonian medicaments or of salivary gland dysfunction e.g. due to radiotherapy of the oral cavity and the head and neck region. Above all, these patients should be aware of the potential demineralization effects of oral hygiene products with low pH and high titratable acids. Acetyl salicylic acid taken regularly in the form of multiple chewable tablets or in the form of headache powder as well chewing hydrochloric acids tablets for treatment of stomach disorders can cause erosion. There is most probably no direct association between asthmatic drugs and erosion on the population level. Consumers, patients and health professionals should be aware of the potential of tooth damage not only by oral hygiene products and salivary substitutes but also by chewable and effervescent tablets. Additionally, it can be assumed that patients suffering from xerostomia should be aware of the potential effects of oral hygiene products with low pH and high titratable acids.

Toxigenic Strains of Bacillus licheniformis Related to Food Poisoning

PubMed Central

Salkinoja-Salonen, M. S.; Vuorio, R.; Andersson, M. A.; Kämpfer, P.; Andersson, M. C.; Honkanen-Buzalski, T.; Scoging, A. C.

1999-01-01

Toxin-producing isolates of Bacillus licheniformis were obtained from foods involved in food poisoning incidents, from raw milk, and from industrially produced baby food. The toxin detection method, based on the inhibition of boar spermatozoan motility, has been shown previously to be a sensitive assay for the emetic toxin of Bacillus cereus, cereulide. Cell extracts of the toxigenic B. licheniformis isolates inhibited sperm motility, damaged cell membrane integrity, depleted cellular ATP, and swelled the acrosome, but no mitochondrial damage was observed. The responsible agent from the B. licheniformis isolates was partially purified. It showed physicochemical properties similar to those of cereulide, despite having very different biological activity. The toxic agent was nonproteinaceous; soluble in 50 and 100% methanol; and insensitive to heat, protease, and acid or alkali and of a molecular mass smaller than 10,000 g mol−1. The toxic B. licheniformis isolates inhibited growth of Corynebacterium renale DSM 20688T, but not all inhibitory isolates were sperm toxic. The food poisoning-related isolates were beta-hemolytic, grew anaerobically and at 55°C but not at 10°C, and were nondistinguishable from the type strain of B. licheniformis, DSM 13T, by a broad spectrum of biochemical tests. Ribotyping revealed more diversity; the toxin producers were divided among four ribotypes when cut with PvuII and among six when cut with EcoRI, but many of the ribotypes also contained nontoxigenic isolates. When ribotyped with PvuII, most toxin-producing isolates shared bands at 2.8 ± 0.2, 4.9 ± 0.3, and 11.7 ± 0.5 or 13.1 ± 0.8 kb. PMID:10508100

Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study.

PubMed

Kimura, Hiroaki; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hideji; Hayashi, Katsuhiro; Tanzawa, Yoshikazu; Takeuchi, Akihiko; Igarashi, Kentaro; Inatani, Hiroyuki; Shimozaki, Shingo; Kato, Takashi; Aoki, Yu; Higuchi, Takashi; Tsuchiya, Hiroyuki

2015-03-01

The first aim of this study was to evaluate combination antiemetic therapy consisting of 5-HT3 receptor antagonists, neurokinin-1 receptor antagonists (NK-1RAs), and dexamethasone for multiple high emetogenic risk (HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting (CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Behavioural profile of exendin-4/naltrexone dose combinations in male rats during tests of palatable food consumption.

PubMed

Wright, F L; Rodgers, R J

2014-09-01

The glucagon-like peptide 1 receptor (GLP-1R) agonist exendin-4 potently suppresses food intake in animals and humans. However, little is known about the behavioural specificity of this effect either when administered alone or when co-administered with another anorectic agent. The present study characterises the effects of exendin-4, both alone and in combination with naltrexone, on behaviours displayed by male rats during tests with palatable mash. Experiment 1 examined the dose-response effects of exendin-4 (0.025-2.5 μg/kg, IP), while experiment 2 profiled the effects of low-dose combinations of the peptide (0.025 and 0.25 μg/kg) and naltrexone (0.1 mg/kg). In experiment 1, exendin-4 dose dependently suppressed food intake as well as the frequency and rate of eating. However, these effects were accompanied by dose-dependent reductions in all active behaviours and, at 2.5 μg/kg, a large increase in resting and disruption of the behavioural satiety sequence (BSS). In experiment 2, while exendin-4 (0.25 μg/kg) and naltrexone each produced a significant reduction in intake and feeding behaviour (plus an acceleration in the BSS), co-treatment failed to produce stronger effects than those seen in response to either compound alone. Similarities between the behavioural signature of exendin-4 and that previously reported for the emetic agent lithium chloride would suggest that exendin-4 anorexia is related to the aversive effects of the peptide. Furthermore, as low-dose combinations of the peptide with naltrexone failed to produce an additive/synergistic anorectic effect, this particular co-treatment strategy would not appear to have therapeutic significance.

Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?

PubMed Central

Fernández-Ruiz, Javier; Sagredo, Onintza; Pazos, M Ruth; García, Concepción; Pertwee, Roger; Mechoulam, Raphael; Martínez-Orgado, José

2013-01-01

Cannabidiol (CBD) is a phytocannabinoid with therapeutic properties for numerous disorders exerted through molecular mechanisms that are yet to be completely identified. CBD acts in some experimental models as an anti-inflammatory, anticonvulsant, anti-oxidant, anti-emetic, anxiolytic and antipsychotic agent, and is therefore a potential medicine for the treatment of neuroinflammation, epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia, respectively. The neuroprotective potential of CBD, based on the combination of its anti-inflammatory and anti-oxidant properties, is of particular interest and is presently under intense preclinical research in numerous neurodegenerative disorders. In fact, CBD combined with Δ9-tetrahydrocannabinol is already under clinical evaluation in patients with Huntington's disease to determine its potential as a disease-modifying therapy. The neuroprotective properties of CBD do not appear to be exerted by the activation of key targets within the endocannabinoid system for plant-derived cannabinoids like Δ9-tetrahydrocannabinol, i.e. CB1 and CB2 receptors, as CBD has negligible activity at these cannabinoid receptors, although certain activity at the CB2 receptor has been documented in specific pathological conditions (i.e. damage of immature brain). Within the endocannabinoid system, CBD has been shown to have an inhibitory effect on the inactivation of endocannabinoids (i.e. inhibition of FAAH enzyme), thereby enhancing the action of these endogenous molecules on cannabinoid receptors, which is also noted in certain pathological conditions. CBD acts not only through the endocannabinoid system, but also causes direct or indirect activation of metabotropic receptors for serotonin or adenosine, and can target nuclear receptors of the PPAR family and also ion channels. PMID:22625422

Intravenous fosfomycin for pulmonary exacerbation of cystic fibrosis: Real life experience of a large adult CF centre.

PubMed

Spoletini, G; Kennedy, M; Flint, L; Graham, T; Etherington, C; Shaw, N; Whitaker, P; Denton, M; Clifton, I; Peckham, D

2018-04-13

The increased prevalence of multi-drug resistant strains of P.aeruginosa and allergic reactions among adult patients with cystic fibrosis (CF) limits the number of antibiotics available to treat pulmonary exacerbations. Fosfomycin, a unique broad spectrum bactericidal antibiotic, might offer an alternative therapeutic option in such cases. To describe the clinical efficacy, safety and tolerability of intravenous fosfomycin in combination with a second anti-pseudomonal antibiotic to treat pulmonary exacerbations in adult patients with CF. A retrospective analysis of data captured prospectively, over a 2-years period, on the Unit electronic medical records for patients who received IV fosfomycin was performed. Baseline characteristics in the 12 months prior treatment, lung function, CRP, renal and liver function and electrolytes at start and end of treatment were retrieved. 54 patients received 128 courses of iv fosfomycin in combination with a second antibiotic, resulting in improved FEV1 (0.94 L vs 1.24 L, p < 0.01) and reduced CRP (65 mg/L vs 19.3 mg/L, p < 0.01). Renal function pre- and post-treatment remained stable. 4% (n = 5) of courses were complicated with AKI at mid treatment, which resolved at the end of the course. Electrolyte supplementation was required in 18% of cases for potassium and magnesium and 7% for phosphate. Nausea was the most common side effects (48%), but was well controlled with anti-emetics. Antibiotic regimens including fosfomycin appear to be clinically effective and safe. Fosfomycin should, therefore, be considered as an add-on therapy in patients who failed to respond to initial treatment and with multiple drug allergies. Copyright © 2018. Published by Elsevier Ltd.

From Chemotherapy-Induced Emesis to Neuroprotection: Therapeutic Opportunities for 5-HT3 Receptor Antagonists.

PubMed

Fakhfouri, Gohar; Mousavizadeh, Kazem; Mehr, Sharam Ejtemaei; Dehpour, Ahmad Reza; Zirak, Mohammad Reza; Ghia, Jean-Eric; Rahimian, Reza

2015-12-01

5-HT3 receptor antagonists are extensively used as efficacious agents in counteracting chemotherapy-induced emesis. Recent investigations have shed light on other potential effects (analgesic, anxiolytic, and anti-psychotic). Some studies have reported neuroprotective properties for the 5-HT3 receptor antagonists in vitro and in vivo. When administered to Aβ-challenged rat cortical neurons, 5-HT3 receptor antagonists substantially abated apoptosis, elevation of cytosolic Ca(2), glutamate release, reactive oxygen species (ROS) generation, and caspase-3 activity. In addition, in vivo studies show that 5-HT3 receptor antagonists possess, alongside their anti-emetic effects, notable immunomodulatory properties in CNS. We found that pretreatment with tropisetron significantly improved neurological deficits and diminished leukocyte transmigration into the brain, TNF-α level, and brain infarction in a murine model of embolic stroke. Our recent investigation revealed that tropisetron protects against Aβ-induced neurotoxicity in vivo through both 5-HT3 receptor-dependent and -independent pathways. Tropisetron, in vitro, was found to be an efficacious inhibitor of the signaling pathway leading to the activation of pro-inflammatory NF-κB, a transcription factor pivotal to the upregulation of several neuroinflammatory mediators in brain. This mini review summarizes novel evidence concerning effects of 5-HT3 antagonists and their possible mechanisms of action in ameliorating neurodegenerative diseases including Alzheimer, multiple sclerosis, and stroke. Further, we discuss some newly synthesized 5-HT3 receptor antagonists with dual properties of 5-HT3 receptor blockade/alpha-7 nicotinic receptor activator and their potential in management of memory impairment. Since 5-HT3 receptor antagonists possess a large therapeutic window, they can constitute a scaffold for design and synthesis of new neuroprotective medications.

Haloperidol dose combined with dexamethasone for PONV prophylaxis in high-risk patients undergoing gynecological laparoscopic surgery: a prospective, randomized, double-blind, dose-response and placebo-controlled study.

PubMed

Joo, Jin; Park, Yong Gyu; Baek, Jungwon; Moon, Young Eun

2015-07-08

Low-dose haloperidol is known to be effective for the prevention of postoperative nausea and vomiting (PONV). However, precise dose-response studies have not been completed, especially in patients at high risk for PONV who require combination therapy. This study sought to identify which dose of haloperidol 1mg or 2mg could be combined with dexamethasone without adverse effects in high-risk patients undergoing gynecological laparoscopic surgery. Female adults (n = 150) with three established PONV risk factors based on Apfel's score were randomized into one of three study groups. At the end of anesthesia, groups H0, H1, and H2 were given intravenous (IV) saline, haloperidol 1 mg, and haloperidol 2 mg, respectively. All patients were given dexamethasone 5 mg during the induction of anesthesia. The overall early (0-2 h) and late (2-24 h) incidences of nausea, vomiting, rescue anti-emetic administration, pain, and adverse effects (cardiac arrhythmias and extrapyramidal effects) were assessed postoperatively. The sedation score was recorded in the postanesthesia care unit (PACU). The total incidence of PONV over 24 h was significantly lower in groups H1 (29 %) and H2 (24 %) than in group H0 (54 %; P = 0.003), but there was no significant difference between groups H1 and H2. In the PACU, group H2 had a higher sedation score than groups H1 and H0 (P < 0.001). For high-risk PONV patients undergoing gynecological laparoscopic surgery, when used with dexamethasone, 1-mg haloperidol was equally effective as 2 mg in terms of preventing PONV with the less sedative effect. ClinicalTrials.gov ( NCT01639599 ).

Assessment of low-dose cisplatin as a model of nausea and emesis in beagle dogs, potential for repeated administration.

PubMed

Kenward, Hannah; Pelligand, Ludovic; Elliott, Jonathan

2014-08-01

Cisplatin is a highly emetogenic cancer chemotherapy agent, which is often used to induce nausea and emesis in animal models. The cytotoxic properties of cisplatin also cause adverse events that negatively impact on animal welfare preventing repeated administration of cisplatin. In this study, we assessed whether a low (subclinical) dose of cisplatin could be utilized as a model of nausea and emesis in the dog while decreasing the severity of adverse events to allow repeated administration. The emetic, nausea-like behavior and potential biomarker response to both the clinical dose (70 mg/m2) and low dose (15 mg/m2) of cisplatin was assessed. Plasma creatinine concentrations and granulocyte counts were used to assess adverse effects on the kidneys and bone marrow, respectively. Nausea-like behavior and emesis was induced by both doses of cisplatin, but the latency to onset was greater in the low-dose group. No significant change in plasma creatinine was detected for either dose groups. Granulocytes were significantly reduced compared with baseline (P = 0.000) following the clinical, but not the low-dose cisplatin group. Tolerability of repeated administration was assessed with 4 administrations of an 18 mg/m2 dose cisplatin. Plasma creatinine did not change significantly. Cumulative effects on the granulocytes occurred, they were significantly decreased (P = 0.03) from baseline at 3 weeks following cisplatin for the 4th administration only. Our results suggest that subclinical doses (15 and 18 mg/m2) of cisplatin induce nausea-like behavior and emesis but have reduced adverse effects compared with the clinical dose allowing for repeated administration in crossover studies.

Effects of maropitant citrate or acepromazine on the incidence of adverse events associated with hydromorphone premedication in dogs.

PubMed

Claude, A K; Dedeaux, A; Chiavaccini, L; Hinz, S

2014-01-01

Vomiting is a common complication associated with the use of hydromorphine for pre-emptive analgesia in dogs. The ideal anti-emetic protocol for prevention of this complication has not been established. Maropitant administered concurrently or before hydromorphone would reduce the incidence of vomiting, signs of nausea, ptyalism, and increased panting compared to administration of acepromazine or a 0.9% saline control. Sixty mixed-breed female dogs scheduled for ovariohysterectomy. Randomized, blinded, placebo-controlled experimental study. Dogs were assigned to 4 experimental groups with 15 dogs per group. All groups received 0.2 mg/kg of hydromorphone IM. Group "Control" received 0.1 mL/kg saline SC 30-45 minutes before hydromorphone, group "Marop1" received 1 mg/kg maropitant SC 30-45 minutes before hydromorphone, group "Ace" received 0.02 mg/kg IM acepromazine 30-45 minutes before hydromorphone, and group "Marop2" received 1 mg/kg SC maropitant concurrently with hydromorphone. A trained and blinded observer documented adverse events from the time hydromorphone was administered until the time dogs were induced for surgery. Marop1 had significantly less vomiting (0%) compared to Control (87%; P < .01) and Ace (53%; P < .01). Marop2 had significantly less vomiting (27%) compared to Control (P < .01). Marop1 had significantly greater incidence of ptyalism (73%) compared to Ace (P < .01; 20%). Ace showed significantly less panting (33%) compared to Marop2 (93%; P < .01). In healthy dogs, maropitant citrate administered before hydromorphone significantly decreases the incidence of vomiting in dogs but does not improve signs of nausea, ptyalism, or increased panting. Copyright © 2014 by the American College of Veterinary Internal Medicine.

Midodrine as a Countermeasure to Orthostatic Hypotension Immediately After Space Shuttle Landing

NASA Technical Reports Server (NTRS)

Platts, Steven H.; Stenger, Michael B.; Ribeiro, L. Christine; Lee, Stuart M. C.

2010-01-01

Midodrine prevents post-space flight orthostatic intolerance when testing is conducted in a controlled laboratory setting within 2-4 hours after Space Shuttle landing. It is unknown if midodrine is as effective during re-entry and immediately following landing. METHODS: Cardiovascular responses to 10 minutes of 80 head-up tilt in five male astronauts were compared before and immediately after Space Shuttle missions. Preflight tests were conducted in the Johnson Space Center Cardiovascular Laboratory without midodrine. Post-flight testing was performed in the Crew Transport Vehicle on the Space Shuttle runway within 60 minutes of landing; midodrine was self-administered before re-entry. Survival analysis was performed (Gehan-Breslow test) to compare presyncope rates pre- to post-flight. Cardiovascular responses (last minute standing minus supine) to tilt before and after space flight were compared using paired t-tests. RESULTS: Midodrine did not prevent post-flight orthostatic hypotension in two of the five astronauts, but the rate of presyncope across the group did not increase (p=0.17) from pre- to post-flight. Also, although the change in heart rate from supine to the last minute of standing was not affected by space flight, systolic blood pressure decreased more (p=0.05) and diastolic blood pressure tended to decrease (p=0.08) after space flight. CONCLUSIONS: Accurate interpretation of the current results requires that similar data be collected in control subjects (without midodrine) on the CTV. However, drug interaction concerns with commonly used anti-emetics and potentiation of prolonged QTc intervals observed in long duration astronauts make the routine use of midodrine for immediate post-flight orthostatic hypotension unlikely. 2

Identification and Quantification of Gingerols and Related Compounds in Ginger Dietary Supplements Using High Performance Liquid Chromatography-Tandem Mass Spectrometry

PubMed Central

TAO, YI; LI, WENKUI; LIANG, WENZHONG; VAN BREEMEN, RICHARD B.

2009-01-01

Dietary supplements containing preparations of ginger roots/rhizomes (Zingiber officinale Roscoe) are being used by consumers, and clinical trials using ginger dietary supplements have been carried out to evaluate their anti-inflammatory or anti-emetic properties with inconsistent results. Chemical standardization of these products is needed for quality control and to facilitate the design of clinical trials and the evaluation of data from these studies. To address this issue, methods based on liquid chromatography-tandem mass spectrometry (LC-MS-MS) were developed for the detection, characterization and quantitative analysis of gingerol-related compounds in botanical dietary supplements containing ginger roots/rhizomes. During negative ion electrospray with collision induced-dissociation, the cleavage of the C4-C5 bond with a neutral loss of 194 u and benzylic cleavage leading to the neutral loss of 136 u were found to be class characteristic fragmentation patterns of the pharmacologically active gingerols or shogaols, respectively. Based on these results, an assay using LC-MS-MS with neutral loss scanning (loss of 194 u or 136 u) was developed that is suitable for the fingerprinting of ginger dietary supplements based on the selective detection of gingerols, shogaols, paradols, and gingerdiones. In addition, a quantitative assay based on LC-MS-MS with selected reaction monitoring was developed for the quantitative analysis of 6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, 8-shogaol, and 10-shogaol in ginger dietary supplements. After method validation, the quantities of these compounds in three commercially available ginger dietary supplements were determined. This assay showed excellent sensitivity, accuracy and precision and may be used to address the need for quality control and standardization of ginger dietary supplements. PMID:19817455

Subcutaneous administration of fentanyl in childbirth: an observational study on the clinical effectiveness of fentanyl for mother and neonate.

PubMed

Fleet, Julie; Jones, Meril; Belan, Ingrid

2014-01-01

to explore the maternal and neonatal effects of fentanyl administered subcutaneously to women during labour. two methods were used: (1) A retrospective audit of the birth register and maternal and neonatal records for the period from January 2000 to December 2007. (2) A pilot study was also conducted on a convenience sample of women between July 2008 and October 2008. this study was conducted within a maternity unit at a rural South Australian hospital where approximately 350 babies are birthed each year. audit participants included women who had uncomplicated pregnancies and birthed at term (37-42 weeks gestation). Women in the experimental group consisted of those who had utilised only subcutaneous fentanyl for pain relief (n=75), or nitrous oxide and oxygen prior to being administered subcutaneous fentanyl (n=196). Stratified random selection based on parity and age was used to determine the control group, which consisted of women who used no pharmacological pain relief (n=196). The pilot study involved a convenience sample of women (n=10) assessed to have an uncomplicated pregnancy and labour occurring at term (≥37 weeks gestation). audit variables examined included the women's age, parity, labour duration, mode of birth (spontaneous or assisted), analgesia used, total dosage, time administered prior to birth, time of birth, neonatal Apgar scores, time to establish breathing, naloxone use, days spent in hospital post-birth and breast-feeding outcomes upon discharge. The pilot study explored maternal effects assessed pre- and 30 minutes post-administration of subcutaneously administered fentanyl by observing pain scores, vital signs, sedation levels, nausea/vomiting scores and anti-emetic use. To assess possible adverse effects in the neonate Apgar scores, time to establish respiration, naloxone use, transfer to neonatal nursery and breast-feeding outcomes upon discharge were recorded. women in the experimental groups were more likely to be induced

Comparison Of The Direct Costs, Length Of Recovery, And Incidence Of Post Operative Anti Emetic Use After Anesthesia Induction With Propofol Or A 1:1 Mixture Of Thiopental And Propofol

DTIC Science & Technology

1999-10-01

1.2% purified egg phosphatide as a stabilizer (Doyle, 1998; Searle & Sahab, 1993). Propofol is rapidly metabolized with less than 20% recovered...affect the neuro transmitter gamma- aminobutyric acid A (GABA A ) receptor sites present in the central nervous system. A GABA A receptor is an...Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system, binds to alpha or beta sub-units on the receptor

Comparison of the Direct Costs, Length of Recovery, and Incidence of Post Operative Anti-Emetic use After Anesthesia Induction with Propofol or a 1:1 Mixture of Thiopental and Propofol

DTIC Science & Technology

1999-10-01

other agent. The net result was enhanced GABA function. Further experiments need to be done to confirm this. Propofol and midazolam (a...REFERENCES Amrein, R., Hetzel, W., & Allen, S. R. (1995). Co-induction of anaesthesia: The rationale. European Journal of Anaesthesiology Supplement...alfentanil for a short gynecological procedure. Acta Anaesthesiology Scandinavia, 40(4), 416-420. 1:1 Mixture 47 Gan, T.J., Ginsberg, B., Grant, A.P

Daily Palonosetron Is Superior to Ondansetron in the Prevention of Delayed Chemotherapy-Induced Nausea and Vomiting in Patients With Acute Myelogenous Leukemia

PubMed Central

Mattiuzzi, Gloria N.; Cortes, Jorge E.; Blamble, Deborah A.; Bekele, B. Nebiyou; Xiao, Lianchun; Cabanillas, Maria; Borthakur, Gautam; O’Brien, Susan; Kantarjian, Hagop

2014-01-01

BACKGROUND Nausea and vomiting in patients with acute myelogenous leukemia (AML) can be from various causes, including the use of high-dose cytarabine. METHODS The authors compared 2 schedules of palonosetron versus ondansetron in the treatment of chemotherapy-induced nausea and vomiting (CINV) in patients with AML receiving high-dose cytarabine. Patients were randomized to: 1) ondansetron, 8 mg intravenously (IV), followed by 24 mg continuous infusion 30 minutes before high-dose cytarabine and until 12 hours after the high-dose cytarabine infusion ended; 2) palonosetron, 0.25 mg IV 30 minutes before chemotherapy, daily from Day 1 of high-dose cytarabine up to Day 5; or 3) palonosetron, 0.25 mg IV 30 minutes before high-dose cytarabine on Days 1, 3, and 5. RESULTS Forty-seven patients on ondansetron and 48 patients on each of the palonosetron arms were evaluable for efficacy. Patients in the palonosetron arms achieved higher complete response rates (no emetic episodes plus no rescue medication), but the difference was not statistically significant (ondansetron, 21%; palonosetron on Days 1–5, 31%; palonosetron on Days 1, 3, and 5, 35%; P = .32). Greater than 77% of patients in each arm were free of nausea on Day 1; however, on Days 2 through 5, the proportion of patients without nausea declined similarly in all 3 groups. On Days 6 and 7, significantly more patients receiving palonosetron on Days 1 to 5 were free of nausea (P = .001 and P = .0247, respectively). CONCLUSIONS The daily assessments of emesis did not show significant differences between the study arms. Patients receiving palonosetron on Days 1 to 5 had significantly less severe nausea and experienced significantly less impact of CINV on daily activities on Days 6 and 7. PMID:21218459

Prescription drugs among pregnant women in Lome, Togo, West Africa.

PubMed

Potchoo, Yao; Redah, Datouda; Gneni, Malick A; Guissou, Innocent P

2009-08-01

To assess the trends in prescription drugs and the potential repercussions to newborns among pregnant women who attended prenatal consultations and gave birth in the Department of Gynaecology of Tokoin's University Hospital, Lome (Togo). A retrospective study of the registers of prenatal visits and deliveries of the eligible population was performed. In total, 184 different drugs were prescribed to 627 pregnant women attending prenatal consultations. The profile of pharmacotherapeutic groups prescribed was: anti-anaemics (33.33%), antimalarial drugs (24.75%), vitamins +/- mineral salts, amino acids and appetite stimulants (14.96%) and antispasmodics and anti-emetics (7.22%). The median proportion of prescriptions for each pharmacotherapeutic group increased significantly from the first to third trimester (9.72, 25.17 and 64.00 respectively; P < 0.05). The median number of drugs prescribed did not vary significantly (P = 0.051) with the age groups, parity (P = 0.068) or obstetrical-gynaecological history (P = 0.401); it did, however, increase significantly with the medical-surgical history (P < 0.05). There were complications associated with deliveries that had no obvious cause related to drug prescription, including four cases of minor defects, 28 stillborns, 65 cases of low birth weight and 27 hospitalised newborns for neonatal diseases. Some interventions were needed for safeguarding the health of the mother, the foetus and the newborn. The trends in obtaining prescription drugs and the consumption of drugs by pregnant women can be assessed using multiple parameters. We limited our study to age groups, gestational age, parity and the medical history of the pregnant woman, profile of pharmacotherapeutic groups, median number of drugs prescribed and the potential risks of the drugs used. The results of our retrospective study were not alarming in terms of neonatal outcomes.

A Paramedic-staffed Helicopter Emergency Medical Service's Response to Winch Missions in Victoria, Australia.

PubMed

Meadley, Ben; Heschl, Stefan; Andrew, Emily; de Wit, Anthony; Bernard, Stephen A; Smith, Karen

2016-01-01

Winching emergency medical care providers from a helicopter to the scene enables treatment of patients in otherwise inaccessible locations, but is not without risks. The objective of this study was to define characteristics of winch missions undertaken by Intensive Care Flight Paramedics (ICFP) in Victoria, Australia with a focus on extraction methods and clinical care delivered at the scene. A retrospective data analysis was performed to identify all winch missions between November 2010 and March 2014. Demographic data, winch characteristics, physiological parameters, and interventions undertaken on scene by the ICFP were extracted. Out of 5,003 missions in the study period, 125 were identified as winch operations. Winter missions were significantly less frequent than those of any other season. Patients were predominantly male (78.4%) and had a mean age of 38 years (±17.6). A total of 109 (87.2%) patients were identified as experiencing trauma with a mean Revised Trauma Score of 7.5288, and isolated limb fractures were the most frequently encountered injury. Falls and vehicle-related trauma were the most common mechanisms of injury. The total median scene duration was 49 minutes (IQR 23-91). Sixty-three patients (50.4%) were extracted using a stretcher, 45 (36.0%) using a hypothermic strop, and 6 (4.8%) via normal rescue strop. Eleven patients (8.8%) were not winched to the helicopter. Vascular access (38.4%), analgesia (44.0%), and anti-emetic administration (28.8%) were the most frequent clinical interventions. Forty-nine patients (39.2%) did not receive any clinical intervention prior to winch extraction. Winch operations in Victoria, Australia consisted predominantly of patients with minor to moderate traumatic injuries. A significant proportion of patients did not require any clinical treatment prior to winching, and among those who did, analgesia was the most frequent intervention. Advanced medical procedures were rarely required prior to winch extraction.

Spore prevalence and toxigenicity of Bacillus cereus and Bacillus thuringiensis isolates from U.S. retail spices.

PubMed

Hariram, Upasana; Labbé, Ronald

2015-03-01

Recent incidents of foodborne illness associated with spices as the vehicle of transmission prompted this examination of U.S. retail spices with regard to Bacillus cereus. This study focused on the levels of aerobic-mesophilic spore-forming bacteria and B cereus spores associated with 247 retail spices purchased from five states in the United States. Samples contained a wide range of aerobic-mesophilic bacterial spore counts (< 200 to 8.3 × 10(7) CFU/g), with 19.1% of samples at levels above 10(5) CFU/g. For examples, paprika, allspice, peppercorns, and mixed spices had high levels of aerobic spores (> 10(7) CFU/g). Using a novel chromogenic agar, B. cereus and B. thuringiensis spores were isolated from 77 (31%) and 11 (4%) samples, respectively. Levels of B. cereus were <3 to 1,600 MPN/g. Eighty-eight percent of B. cereus isolates and 91% of B. thuringiensis isolates possessed at least one type of enterotoxin gene: HBL (hemolysin BL) or nonhemolytic enterotoxin (NHE). None of the 88 isolates obtained in this study possessed the emetic toxin gene (ces). Using commercially available immunological toxin detection kits, the toxigenicity of the isolates was confirmed. The NHE enterotoxin was expressed in 98% of B. cereus and 91% of B. thuringiensis isolates that possessed the responsible gene. HBL enterotoxin was detected in 87% of B. cereus and 100% of B. thuringiensis PCR-positive isolates. Fifty-two percent of B. cereus and 54% of B. thuringiensis isolates produced both enterotoxins. Ninety-seven percent of B. cereus isolates grew at 12°C, although only two isolates grew well at 9°C. The ability of these spice isolates to form spores, produce diarrheal toxins, and grow at moderately abusive temperatures makes retail spices an important potential vehicle for foodborne illness caused by B. cereus strains, in particular those that produce diarrheal toxins.

A randomized open-label study of guideline-driven antiemetic therapy versus single agent antiemetic therapy in patients with advanced cancer and nausea not related to anticancer treatment.

PubMed

Hardy, Janet; Skerman, Helen; Glare, Paul; Philip, Jennifer; Hudson, Peter; Mitchell, Geoffrey; Martin, Peter; Spruyt, Odette; Currow, David; Yates, Patsy

2018-05-02

Nausea/vomiting (N/V) not related to anti-cancer treatment is common in patients with advanced cancer. The standard approach to management is to define a dominant cause, and treat with an antiemetic selected through pathophysiologic knowledge of emetic pathways. High rates of N/V control have been reported using both etiology-based guideline-driven antiemetic regimens and an empiric approach using single agents in uncontrolled studies. These different approaches had never been formally compared. This randomized, prospective, open label, dose-escalating study used readily available antiemetics in accordance with etiology-based guidelines or single agent therapy with haloperidol. Participants had a baseline average nausea score of ≥3/10. Response was defined as a ≥ 2/10 point reduction on a numerical rating scale of average nausea score with a final score < 3/10 at 72 h. Nausea scores and distress from nausea improved over time in the majority of the 185 patients randomized. For those who completed each treatment day, a greater response rate was seen in the guideline arm than the single agent arm at 24 h (49% vs 32%; p = 0.02), but not at 48 or 72 h. Response rates at 72 h in the intention to treat analysis were 49 and 53% respectively, with no significant difference between arms (0·04; 95% CI: -0·11, 0·19; p = 0·59). Over 80% of all participants reported an improved global impression of change. There were few adverse events worse than baseline in either arm. An etiology-based, guideline-directed approach to antiemetic therapy may offer more rapid benefit, but is no better than single agent treatment with haloperidol at 72 h. Australian New Zealand Clinical Trials Registry: ANZCTRN12610000481077 .

FFPM, a PDE4 inhibitor, reverses learning and memory deficits in APP/PS1 transgenic mice via cAMP/PKA/CREB signaling and anti-inflammatory effects.

PubMed

Guo, Haibiao; Cheng, Yufang; Wang, Canmao; Wu, Jingang; Zou, Zhengqiang; Niu, Bo; Yu, Hui; Wang, Haitao; Xu, Jiangping

2017-04-01

Thus far, phosphodiesterase-4 (PDE4) inhibitors have not been approved for application in Alzheimer's disease (AD) in a clinical setting due to severe side effects, such as nausea and vomiting. In this study, we investigated the effect of FFPM, a novel PDE4 inhibitor, on learning and memory abilities, as well as the underlying mechanism in the APP/PS1 mouse model of AD. Pharmacokinetic studies have revealed that FFPM efficiently permeates into the brain, and reached peak values in plasma 2 h after orally dosing. A 3-week treatment with FFPM, at doses of 0.25 mg/kg and 0.5 mg/kg, significantly improved the learning and memory abilities of APP/PS1 transgenic mice in the Morris water maze and the Step-down passive avoidance task. Interestingly, we found that while rolipram (0.5 mg/kg) reduced the duration of the α2 adrenergic receptor-mediated anesthesia induced by xylazine/ketamine, FFPM (0.5 mg/kg) or the vehicle did not have an evident effect. FFPM increased the cAMP, PKA and CREB phosphorylation and BDNF levels, and reduced the NF-κB p65, iNOS, TNF-α and IL-1β levels in the hippocampi of APP/PS1 trangenic mice, as observed by ELISA and Western blot analysis. Taken together, our data demonstrated that the reversal effect of FFPM on cognitive deficits in APP/PS1 transgenic mice might be related to stimulation of the cAMP/PKA/CREB/BDNF pathway and anti-inflammatory effects. Moreover, FFPM appears to have potential as an effective PDE4 inhibitor in AD treatment with little emetic potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enhanced tolerability of the 5-hydroxytryptophane challenge test combined with granisetron.

PubMed

Jacobs, G E; Kamerling, I M C; de Kam, M L; Derijk, R H; van Pelt, J; Zitman, F G; van Gerven, J M A

2010-01-01

A recently developed oral serotonergic challenge test consisting of 5-Hydroxytryptophane (5-HTP, 200 mg) combined with carbidopa (CBD, 100 mg + 50 mg) exhibited dose-related neuroendocrine responsiveness and predictable pharmacokinetics. However, its applicability is limited by nausea and vomiting. A randomized, double-blind, placebo-controlled, four-way crossover trial was performed in 12 healthy male volunteers. The 5-HTP/CBD-challenge was combined with two oral anti-emetics (granisetron, 2 mg or domperidone, 10 mg) to investigate its reliability when side-effects are suppressed. The neuroendocrine response (serum cortisol and prolactin), the side-effect profile [Visual Analogue Scale Nausea (VAS)] and vomiting subjects per treatment were the main outcome measures. Compared to 5-HTP/CBD/placebo, 5-HTP/CBD/ granisetron had no impact on cortisol [% change with 95% confidence interval: -7.1% (18.9; 6.5)] or prolactin levels [-9.6% (-25.1; 9.1)]; 5-HTP/CBD/domperidone increased cortisol [+13.0% (-4.2; 33.4)], and increased prolactin extensively [+336.8% (245.7; 451.9)]. Compared to placebo, VAS Nausea increased non-significantly with granisetron [+7.6 mm (-1.3; 16.5)], as opposed to domperidone [+16.2 mm (7.2; 25.2)] and 5-HTP/CBD/placebo [+14.7 mm (5.5; 23.8)]. No subjects vomited with granisetron, compared to two subjects treated with 5-HTP/CBD/placebo and five subjects with domperidone. Compared with 5-HTP/CBD/placebo, granisetron addition decreased C(max) of 5-HTP statistically significantly different (from 1483 to 1272 ng/ml) without influencing AUC(0- infinity). Addition of granisetron to the combined 5-HTP/CBD challenge suppresses nausea and vomiting without influencing the neuroendocrine response or pharmacokinetics, enhancing its clinical applicability in future psychiatric research and drug development.

Prescription Patterns and the Cost of Migraine Treatments in German General and Neurological Practices.

PubMed

Jacob, Louis; Kostev, Karel

2017-07-01

The aim of this study was to analyze prescription patterns and the cost of migraine treatments in general practices (GPs) and neurological practices (NPs) in Germany. This study included 43,149 patients treated in GPs and 13,674 patients treated in NPs who were diagnosed with migraine in 2015. Ten different families of migraine therapy were included in the analysis: triptans, analgesics, anti-emetics, beta-blockers, antivertigo products, gastroprokinetics, anti-epileptics, calcium channel blockers, tricyclic antidepressants, and other medications (all other classes used in the treatment of migraine including homeopathic medications). The share of migraine therapies and their costs were estimated for GPs and NPs. The mean age was 44.4 years in GPs and 44.1 years in NPs. Triptans and analgesics were the 2 most commonly prescribed families of drugs in all patients and in the 9 specific subgroups. Interestingly, triptans were more commonly prescribed in NPs than in GPs (30.9% to 55.0% vs. 30.0% to 44.7%), whereas analgesics were less frequently given in NPs than in GPs (11.5% to 17.2% vs. 35.3% to 42.4%). Finally, the share of patients who received no therapy was higher in NPs than in GPs (33.9% to 58.4% vs. 27.5% to 37.9%). The annual cost per patient was €66.04 in GPs and €94.71 in NPs. Finally, the annual cost per patient increased with age and was higher in women and in individuals with private health insurance coverage than in men and individuals with public health insurance coverage. Triptans and analgesics were the 2 most commonly prescribed drugs for the treatment of migraine. Furthermore, approximately 30% to 40% of patients did not receive any therapy. Finally, the annual cost per patient was higher in NPs than in GPs. © 2016 World Institute of Pain.

Peptide YY3–36 and 5-Hydroxytryptamine Mediate Emesis Induction by Trichothecene Deoxynivalenol (Vomitoxin)

PubMed Central

Pestka, James J.

2013-01-01

Deoxynivalenol (DON, vomitoxin), a trichothecene mycotoxin produced by Fusarium sp. that frequently occurs in cereal grains, has been associated with human and animal food poisoning. Although a common hallmark of DON-induced toxicity is the rapid onset of emesis, the mechanisms for this adverse effect are not fully understood. Recently, our laboratory has demonstrated that the mink (Neovison vison) is a suitable small animal model for investigating trichothecene-induced emesis. The goal of this study was to use this model to determine the roles of two gut satiety hormones, peptide YY3–36 (PYY3–36) and cholecystokinin (CCK), and the neurotransmitter 5-hydroxytryptamine (5-HT) in DON-induced emesis. Following ip exposure to DON at 0.1 and 0.25mg/kg bw, emesis induction ensued within 15–30min and then persisted up to 120min. Plasma DON measurement revealed that this emesis period correlated with the rapid distribution and clearance of the toxin. Significant elevations in both plasma PYY3–36 (30–60min) and 5-HT (60min) but not CCK were observed during emesis. Pretreatment with the neuropeptide Y2 receptor antagonist JNJ-31020028 attenuated DON- and PYY-induced emesis, whereas the CCK1 receptor antagonist devezapide did not alter DON’s emetic effects. The 5-HT3 receptor antagonist granisetron completely suppressed induction of vomiting by DON and the 5-HT inducer cisplatin. Granisetron pretreatment also partially blocked PYY3–36-induced emesis, suggesting a potential upstream role for this gut satiety hormone in 5-HT release. Taken together, the results suggest that both PYY3–36 and 5-HT play contributory roles in DON-induced emesis. PMID:23457120

Economic analysis of aprepitant-containing regimen to prevent chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy in Hong Kong.

PubMed

Chan, Stephen L; Jen, Jason; Burke, Thomas; Pellissier, James

2014-03-01

We aim to evaluate the cost effectiveness of aprepitant-containing regimens for the prevention of chemotherapy-induced nausea and vomiting (CINV) among patients receiving high emetogenic chemotherapy (HEC) in Hong Kong. Both cost-effectiveness and cost-utility analyses were conducted utilizing a decision-analytic model to measure the economic costs and clinical outcomes associated with the aprepitant-containing regimen versus a standard regimen in the prevention of CINV. Analyses were conducted on the basis of four published double-blind randomized clinical trials involving different usages of serotonin receptor antagonists. The use of aprepitant-containing regimens is associated with an improvement in quality-adjusted life years (QALYs) compared with non-aprepitant regimens. For cisplatin-based chemotherapy, the incremental cost per QALY gained is HKD 239,644 (1 USD approximates HKD 7.8) when ondansetron is administered on day 1 only. The incremental cost per QALY is HKD 440,950 when ondansetron is used on day 1 to 4. For anthracycline and cyclophosphamide chemotherapy, the aprepitant-containing regimen is associated with incremental cost of HKD 195,442 per QALY gained. Similar results were obtained when other 5HT3 receptor antagonists are used. The use of aprepitant was associated with higher cost of drug but lower costs of emesis-related management. With the cost-effectiveness threshold set at the World Health Organization endorsed criteria of three times gross domestic product (GDP) per capita (three times GDP per capita in Hong Kong in 2011 is HKD 798,078), the current analyses showed that the aprepitant-containing regimen was cost-effective. In patients undergoing HEC, the use of aprepitant as the anti-emetic is cost-effective in Hong Kong. © 2014 Wiley Publishing Asia Pty Ltd.

Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?

PubMed

Fernández-Ruiz, Javier; Sagredo, Onintza; Pazos, M Ruth; García, Concepción; Pertwee, Roger; Mechoulam, Raphael; Martínez-Orgado, José

2013-02-01

Cannabidiol (CBD) is a phytocannabinoid with therapeutic properties for numerous disorders exerted through molecular mechanisms that are yet to be completely identified. CBD acts in some experimental models as an anti-inflammatory, anticonvulsant, anti-oxidant, anti-emetic, anxiolytic and antipsychotic agent, and is therefore a potential medicine for the treatment of neuroinflammation, epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia, respectively. The neuroprotective potential of CBD, based on the combination of its anti-inflammatory and anti-oxidant properties, is of particular interest and is presently under intense preclinical research in numerous neurodegenerative disorders. In fact, CBD combined with Δ(9)-tetrahydrocannabinol is already under clinical evaluation in patients with Huntington's disease to determine its potential as a disease-modifying therapy. The neuroprotective properties of CBD do not appear to be exerted by the activation of key targets within the endocannabinoid system for plant-derived cannabinoids like Δ(9)-tetrahydrocannabinol, i.e. CB(1) and CB(2) receptors, as CBD has negligible activity at these cannabinoid receptors, although certain activity at the CB(2) receptor has been documented in specific pathological conditions (i.e. damage of immature brain). Within the endocannabinoid system, CBD has been shown to have an inhibitory effect on the inactivation of endocannabinoids (i.e. inhibition of FAAH enzyme), thereby enhancing the action of these endogenous molecules on cannabinoid receptors, which is also noted in certain pathological conditions. CBD acts not only through the endocannabinoid system, but also causes direct or indirect activation of metabotropic receptors for serotonin or adenosine, and can target nuclear receptors of the PPAR family and also ion channels. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Mice deficient in phosphodiesterase-4A display anxiogenic-like behavior.

PubMed

Hansen, Rolf T; Conti, Marco; Zhang, Han-Ting

2014-08-01

Phosphodiesterases (PDEs) are a super family of enzymes responsible for the halting of intracellular cyclic nucleotide signaling and may represent novel therapeutic targets for treatment of cognitive disorders. PDE4 is of considerable interest to cognitive research because it is highly expressed in the brain, particularly in the cognition-related brain regions. Recently, the functional role of PDE4B and PDE4D, two of the four PDE4 subtypes (PDE4A, B, C, and D), in behavior has begun to be identified; however, the role of PDE4A in the regulation of behavior is still unknown. The purpose of this study was to characterize the functional role of PDE4A in behavior. The role of PDE4A in behavior was evaluated through a battery of behavioral tests using PDE4A knockout (KO) mice; urine corticosterone levels were also measured. PDE4A KO mice exhibited improved memory in the step-through-passive-avoidance test. They also displayed anxiogenic-like behavior in elevated-plus maze, holeboard, light-dark transition, and novelty suppressed feeding tests. Consistent with the anxiety profile, PDE4A KO mice had elevated corticosterone levels compared with wild-type controls post-stress. Interestingly, PDE4A KO mice displayed no change in object recognition, Morris water maze, forced swim, tail suspension, and duration of anesthesia induced by co-administration of xylazine and ketamine (suggesting that PDE4A KO may not be emetic). These results suggest that PDE4A may be important in the regulation of emotional memory and anxiety-like behavior, but not emesis. PDE4A could possibly represent a novel therapeutic target in the future for anxiety or disorders affecting memory.

Taste-aversion-prone (TAP) rats and taste-aversion-resistant (TAR) rats differ in ethanol self-administration, but not in ethanol clearance or general consumption.

PubMed

Orr, T Edward; Whitford-Stoddard, Jennifer L; Elkins, Ralph L

2004-05-01

Taste-aversion (TA)-prone (TAP) rats and TA-resistant (TAR) rats have been developed by means of bidirectional selective breeding on the basis of their behavioral responses to a TA conditioning paradigm. The TA conditioning involved the pairing of an emetic-class agent (cyclophosphamide) with a novel saccharin solution as the conditioned stimulus. Despite the absence of ethanol in the selective breeding process, these rat lines differ widely in ethanol self-administration. In the current study, blood alcohol concentrations (BACs) were determined after 9 days of limited (2 h per day) access to a simultaneous, two-bottle choice of a 10% ethanol in water solution [volume/volume (vol./vol.)] or plain water. The BACs correlated highly with ethanol intake among TAR rats, but an insufficient number of TAP rats yielded measurable BACs to make the same comparison within this rat line. The same rats were subsequently exposed to 24-h access of a two-bottle choice (10% ethanol or plain water) for 8 days. Ethanol consumption during the 24-h access period correlated highly with that seen during limited access. Subsequent TA conditioning with these rats yielded line-typical differences in saccharin preferences. In a separate group of rats, ethanol clearance was determined by measuring BACs at 1, 4, and 7 h after injection of a 2.5-g/kg dose of ethanol. Ethanol clearance was not different between the two lines. Furthermore, the lines did not differ with respect to food and water consumption. Therefore, the TAP rat-TAR rat differences in ethanol consumption cannot be attributed to line differences in ethanol metabolism or in general consummatory behavior. The findings support our contention that the line differences in ethanol consumption are mediated by differences in TA-related mechanisms. The findings are discussed with respect to genetically based differences in the subjective experience of ethanol.

A randomized, blinded, controlled trial of the antiemetic effect of ondansetron on dexmedetomidine-induced emesis in cats.

PubMed

Santos, Luiz Cesar P; Ludders, John W; Erb, Hollis N; Martin-Flores, Manuel; Basher, Karen L; Kirch, Pati

2011-07-01

To determine the effect of ondansetron on the incidence of vomiting in cats pre-medicated with dexmedetomidine and buprenorphine. Randomized, blinded, controlled trial. Eighty-nine female domestic shorthair cats, aged 3-60 months (median, 12 months) and weighing 1.2-5.1 kg. Each cat received dexmedetomidine (40 μg kg(-1)) plus buprenorphine (20 μg kg(-1)), intramuscularly as pre-anesthetic medication. Cats were assigned to three treatment groups: ondansetron (0.22 mg kg(-1), intramuscular [IM]), either 30 minutes before the pre-anesthetic medication (ONDA group, n = 31) or with the pre-anesthetic medication (OPM group, n = 30) mixed with the pre-anesthetic medications in the same syringe, or not to receive the antiemetic (control group, n = 28). Emesis was recorded as an all-or-none response. The number of episodes of emesis and the time until onset of the first emetic episode were recorded for each cat. Clinical signs of nausea were recorded whenever they occurred, and a numerical rating scale was used to quantify these signs. Data were analyzed using Kruskal-Wallis and Chi-square test; a Bonferroni correction was made for six comparisons; thus, the two-sided p for significance was 0.05/6 = 0.008. There was a significant reduction in the number of cats vomiting, in the episodes of vomiting/cat, the time elapsed between the premedication and the first vomiting and the severity of nausea in the OPM group compared to the ONDA and control groups. In cats, the administration of ondansetron (0.22 mg kg(-1)) ameliorates and reduced the severity of dexmedetomidine-induced nausea and vomiting only when it was administered in association with this drug. © 2011 The Authors. Veterinary Anaesthesia and Analgesia. © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Antimicrobial susceptibility and β-lactamase production in Bacillus cereus isolates from stool of patients, food and environment samples.

PubMed

Savić, Dejana; Miljković-Selimović, Biljana; Lepšanović, Zorica; Tambur, Zoran; Konstantinović, Sonja; Stanković, Nemanja; Ristanović, Elizabeta

2016-10-01

Bacillus cereus (B. cereus) usually ingested by food can cause two types of diseases: vomiting due to the presence of emetic toxin and diarrheal syndrome, due to the presence of diarrheal toxins. Systemic manifestations can also occur. The severe forms of disease demand antibiotic treatmant. The aim of this study was to determine the differences in antibiotic susceptibility and β-lactamase activity of B. cereus isolates from stools of humans, food and environment. Identification of B. cereus was performed with selective medium, classical biochemical test and polymerase chain reaction (PCR) with primers specific for bal gene. Thirty isolates from each group were analysed for antibiotic susceptibility using the disk-diffusion assay. Production of β-lactamase was determined by cefinase test, and double-disc method. All strains identified as B. cereus using classical biochemical test, yielded 533 bp fragment with PCR. Isolates from all the three groups were susceptible to imipenem, vancomycin, and erythromycin. All isolates were susceptible to ciprofloxacin but one from the environment. A statistically significant difference between the groups was confirmed to tetracycline and trimethoprim-sulphamethoxazole sensitivity. A total of 28/30 (93.33%) samples from the foods and 25/30 (83.33%) samples from environment were approved sensitive to tetracycline, while 10/30 (33.33%) isolates from stools were sensitive. Opposite to this result, high susceptibility to trimethoprim-sulphamethoxazole was shown in samples from stools (100%), while isolates from foods (63.33%) and from environment (70%) had low susceptibility. All samples produced β-lactamases. The strains of B. cereus from all the three groups showed high rate of sensitivity to most tested antibiotics, except to tetracycline in samples from human stool and to trimethoprim-sulphamethoxazole in samples from food and environment. The production of β-lactamases was confirmed in all the strains.

The Therapeutic Potential of Targeting Substance P/NK-1R Interactions in Inflammatory CNS Disorders

PubMed Central

Johnson, M. Brittany; Young, Ada D.; Marriott, Ian

2017-01-01

The inflammatory responses of resident central nervous system (CNS) cells are now known to play a critical role in the initiation and progression of an array of infectious and sterile neuroinflammatory disorders such as meningitis, encephalitis, Parkinson’s disease, Alzheimer’s disease and multiple sclerosis (MS). Regulating glial inflammatory responses in a timely manner is therefore critical in preserving normal CNS functions. The neuropeptide substance P is produced at high levels within the CNS and its selective receptor, the neurokinin 1 receptor (NK-1R), is abundantly expressed by neurons and is present on glial cell types including microglia and astrocytes. In addition to its functions as a neurotransmitter in the perception of pain and its essential role in gut motility, this tachykinin is widely recognized to exacerbate inflammation at peripheral sites including the skin, gastrointestinal tract and the lungs. Recently, a number of studies have identified a role for substance P and NK-1R interactions in neuroinflammation and described the ability of this neuropeptide to alter the immune functions of activated microglia and astrocytes. In this review article, we describe the expression of substance P and its receptor by resident CNS cells, and we discuss the ability of this neuropeptide to exacerbate the inflammatory responses of glia and immune cells that are recruited to the brain during neurodegenerative diseases. In addition, we discuss the available data indicating that the NK-1R-mediated augmentation of such responses appears to be detrimental during microbial infection and some sterile neurodegenerative disorders, and propose the repurposed use of NK-1R antagonists, of a type that are currently approved as anti-emetic and anti-anxiolytic agents, as an adjunct therapy to ameliorate the inflammatory CNS damage in these conditions. PMID:28101005

Cannabinoids suppress synaptic input to neurones of the rat dorsal motor nucleus of the vagus nerve

PubMed Central

Derbenev, Andrei V; Stuart, Thomas C; Smith, Bret N

2004-01-01

Cannabinoids bind central type 1 receptors (CB1R) and modify autonomic functions, including feeding and anti-emetic behaviours, when administered peripherally or into the dorsal vagal complex. Western blots and immunohistochemistry indicated the expression of CB1R in the rat dorsal vagal complex, and tissue polymerase chain reaction confirmed that CB1R message was made within the region. To identify a cellular substrate for the central autonomic effects of cannabinoids, whole-cell patch-clamp recordings were made in brainstem slices to determine the effects of CB1R activation on synaptic transmission to neurones of the dorsal motor nucleus of the vagus (DMV). A subset of these neurones was identified as gastric related after being labelled retrogradely from the stomach. The CB1R agonists WIN55,212-2 and anandamide decreased the frequency of spontaneous excitatory or inhibitory postsynaptic currents in a concentration-related fashion, an effect that persisted in the presence of tetrodotoxin. Paired pulse ratios of electrically evoked postsynaptic currents were also increased by WIN55,212-2. The effects of WIN55,212-2 were sensitive to the selective CB1R antagonist AM251. Cannabinoid agonist effects on synaptic input originating from neurones in the nucleus tractus solitarius (NTS) were determined by evoking activity in the NTS with local glutamate application. Excitatory and inhibitory synaptic inputs arising from the NTS were attenuated by WIN55,212-2. Our results indicate that cannabinoids inhibit transfer of synaptic information to the DMV, including that arising from the NTS, in part by acting at receptors located on presynaptic terminals contacting DMV neurones. Inhibition of synaptic input to DMV neurones is likely to contribute to the suppression of visceral motor responses by cannabinoids. PMID:15272041

Palonosetron with aprepitant plus dexamethasone to prevent chemotherapy-induced nausea and vomiting during gemcitabine/cisplatin in urothelial cancer patients.

PubMed

Kitamura, Hiroshi; Takahashi, Atsushi; Hotta, Hiroshi; Kato, Ryuichi; Kunishima, Yasuharu; Takei, Fumiyasu; Horita, Hiroki; Masumori, Naoya

2015-10-01

To evaluate the appearance of chemotherapy-induced nausea and vomiting, and to compare the antiemetic efficacy of the triple combination of palonosetron, aprepitant and dexamethasone with that of our old regimen using first-generation 5-hydroxytryptamine 3-receptor antagonists and dexamethasone during gemcitabine and cisplatin chemotherapy in patients with advanced urothelial cancer. We carried out a multi-institutional study including 122 patients who received gemcitabine and cisplatin for advanced urothelial cancer between February 2005 and January 2012. Uncontrolled chemotherapy-induced nausea and vomiting events were identified through records of nausea and vomiting, additional infusion, rescue medications, and/or records of food intake. First-generation 5-hydroxytryptamine 3-receptor antagonists (ondansetron or granisetron) plus dexamethasone were used for 75 patients (cohort 1), and palonosetron with dexamethasone plus aprepitant for 47 patients (cohort 2). Patients in cohort 2 had significantly higher complete response (defined as no emetic episodes and no rescue medication use) rates than those in cohort 1 during the overall phase in the first cycle (85.7% vs 65.3%, P = 0.012), and all cycles (78.7% vs 50.7%, P = 0.0019) of gemcitabine and cisplatin. Patients in cohort 2 were more likely to achieve more favorable chemotherapy-induced nausea and vomiting control; that is, a lower grade of nausea, vomiting or anorexia, lower incidence of rescue therapy required, and shorter time to become chemotherapy-induced nausea- and vomiting-free than patients in cohort 1. The present results show that palonosetron in combination with aprepitant and dexamethasone is more effective to prevent chemotherapy-induced nausea and vomiting in urothelial cancer patients treated with gemcitabine and cisplatin than first-generation 5-hydroxytryptamine 3-receptor antagonists plus dexamethasone. © 2015 The Japanese Urological Association.

The effect of duration of dose delivery with patient-controlled analgesia on the incidence of nausea and vomiting after hysterectomy

PubMed Central

Woodhouse, Annie; Mather, Laurence E

1998-01-01

Aims Postoperative nausea and vomiting (PONV) may be exacerbated by postoperative opioid analgesics and may limit patients’ successful use of these medications when used with patient controlled analgesia (PCA). We tested the hypothesis that the rapid change in blood morphine concentration associated with PCA bolus delivery contributed to PONV, and that prolonging its delivery to a brief infusion would result in decreased PONV. Methods Patients, who were receiving morphine for pain relief via patient-controlled analgesia (PCA) after total abdominal hysterectomy, received 1 mg morphine sulphate incremental doses either over 40 s with a 5 min lockout interval or over 5 min delivery with a 1 min lockout interval. Episodes of nausea, retching and vomiting, along with the use of morphine and the pain relief obtained, were recorded. Results Data from 20 patients in each group were analysed. Contrary to expectations, most patients in both groups reported nausea postoperatively. Those patients receiving morphine over 5 min experienced more episodes of emesis (36) than those receiving the dose over 40 s (17). Most patients receiving the 40 s doses vomited in the first 12 h (median time 8 h), while those receiving the 5 min doses vomited between 12 and 24 h (median time 19 h) (P=0.01). There were no differences between groups in the visual analogue pain scores or use of morphine between groups. Conclusions Reasons for these unexpected findings remain speculative. The high incidence of PONV appears to be inherently high in gynaecological surgery patients and standard antiemetic medication regimens appear to be poorly efficacious. Reasons for the differences in the time-course of emetic episodes between the two groups may be related to differences in the time-course of central opioid receptor occupancy. PMID:9489595

Synthesis, Pharmacological Profile and Docking Studies of New Sulfonamides Designed as Phosphodiesterase-4 Inhibitors

PubMed Central

Cardozo, Suzana Vanessa S.; Carvalho, Vinicius de Frias; Romeiro, Nelilma Correia; Silva, Patrícia Machado Rodrigues e; Martins, Marco Aurélio; Barreiro, Eliezer J.; Lima, Lídia Moreira

2016-01-01

Prior investigations showed that increased levels of cyclic AMP down-regulate lung inflammatory changes, stimulating the interest in phosphodiesterase (PDE)4 as therapeutic target. Here, we described the synthesis, pharmacological profile and docking properties of a novel sulfonamide series (5 and 6a-k) designed as PDE4 inhibitors. Compounds were screened for their selectivity against the four isoforms of human PDE4 using an IMAP fluorescence polarized protocol. The effect on allergen- or LPS-induced lung inflammation and airway hyper-reactivity (AHR) was studied in A/J mice, while the xylazine/ketamine-induced anesthesia test was employed as a behavioral correlate of emesis in rodents. As compared to rolipram, the most promising screened compound, 6a (LASSBio-448) presented a better inhibitory index concerning PDE4D/PDE4A or PDE4D/PDE4B. Accordingly, docking analyses of the putative interactions of LASSBio-448 revealed similar poses in the active site of PDE4A and PDE4C, but slight unlike orientations in PDE4B and PDE4D. LASSBio-448 (100 mg/kg, oral), 1 h before provocation, inhibited allergen-induced eosinophil accumulation in BAL fluid and lung tissue samples. Under an interventional approach, LASSBio-448 reversed ongoing lung eosinophilic infiltration, mucus exacerbation, peribronchiolar fibrosis and AHR by allergen provocation, in a mechanism clearly associated with blockade of pro-inflammatory mediators such as IL-4, IL-5, IL-13 and eotaxin-2. LASSBio-448 (2.5 and 10 mg/kg) also prevented inflammation and AHR induced by LPS. Finally, the sulfonamide derivative was shown to be less pro-emetic than rolipram and cilomilast in the assay employed. These findings suggest that LASSBio-448 is a new PDE4 inhibitor with marked potential to prevent and reverse pivotal pathological features of diseases characterized by lung inflammation, such as asthma. PMID:27695125

Action of (R)-sila-venlafaxine and reboxetine to antagonize cisplatin-induced acute and delayed emesis in the ferret

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warneck, Julie B.; Cheng, Frankie H.M.; Barnes, Matthew J.

2008-11-01

The chemotherapeutic drug cisplatin is associated with severe gastrointestinal toxicity that can last for several days. A recent strategy to treat the nausea and emesis includes the combination of a 5-HT{sub 3} receptor antagonist, a glucocorticoid, and an NK{sub 1} receptor antagonist. The present studies explore the use of the selective noradrenaline reuptake inhibitors, (R)-sila-venlafaxine, (R,R)-reboxetine and (S,S)-reboxetine to prevent cisplatin (5 mg/kg, i.p.)-induced acute (0-24 h) and delayed (24-72 h) emesis in ferrets. The positive control regimen of ondansetron and dexamethasone, both at 1 mg/kg/8 h, reduced acute and delayed emesis by 100 (P < 0.001) and 61% (Pmore » < 0.05). (R)-sila-venlafaxine at 5 and 15 mg/kg/4 h reduced acute emesis by 86 (P < 0.01) and 66% (P < 0.05), respectively and both enantiomers of reboxetine at 1 mg/kg/12 h also reduced the response by {approx} 70-90% (P < 0.05). Out of the reuptake inhibitors, only (R)-sila-venlafaxine at 15 mg/kg/4 h was active to reduce delayed emesis (a 57% reduction was observed (P < 0.05)); its terminal plasma levels were positively correlated with an inhibition of emesis during the delayed phase (P < 0.05). (R)-sila-venlafaxine was also examined against a higher dose of cisplatin 10 mg/kg, i.p. (3 h test) and it dose-dependently antagonized the response (maximum reduction was 94% at 10 mg/kg, p.o.; P < 0.01) but it was ineffective against apomorphine (0.125 mg/kg, s.c.) and ipecacuanha (2 mg/kg, p.o.)-induced emesis (P > 0.05). In conclusion, the studies provide the first evidence for an anti-emetic potential of noradrenaline reuptake inhibitors to reduce chemotherapy-induced acute and delayed emesis.« less

Zinc-carnosine and vitamin E supplementation does not ameliorate gastrointestinal side effects associated with ciclosporin therapy of canine atopic dermatitis.

PubMed

Wilson, Laura S; Rosenkrantz, Wayne S; Roycroft, Linda M

2011-02-01

Chelated zinc-carnosine and vitamin E [GastriCalm(®) (GCM); Teva Animal Health] is marketed as an anti-emetic supplement for dogs to assist the repair of damaged stomach and intestinal mucosa. The purpose of this prospective, double-blinded, placebo-controlled trial was to determine whether GCM reduced the frequency of vomiting, diarrhoea and appetite changes during initiation of ciclosporin (Atopica(®); Novartis Animal Health) therapy for the treatment of canine atopic dermatitis. Sixty privately owned dogs diagnosed with atopic dermatitis were randomly assigned to GCM (n=30) or placebo (n=30) groups. All dogs received ∼ 5 mg/kg ciclosporin (range, 3.5-5.8 mg/kg) once daily. Dogs <13.6 kg received half a tablet of GCM or placebo; dogs ≥ 13.6 kg received one tablet once daily. GastriCalm(®) or placebo was administered 30 min prior to eating, and the ciclosporin was administered 2 h after feeding. Owners recorded episodes of vomiting, diarrhoea and appetite changes. Dogs were examined on days 0 and 14. Forty-one of 60 dogs (68.3%) had at least one episode of vomiting, diarrhoea or appetite change, leaving nine placebo dogs (30%) and ten GCM dogs (33.3%) free of adverse events (AE). Twenty-seven of 60 dogs (45%) vomited, and 15 of 60 (25%) had diarrhoea. There was no significant difference in episodes of individual AEs, but the placebo group had a significantly lower total AE score (summation of episodes of appetite change, vomiting and diarrhoea; P=0.022). Small dogs (<6.82 kg) had significantly fewer total AEs in both treatment groups and tolerated ciclosporin better than larger dogs (P<0.05). © 2010 The Authors. Journal compilation © 2010 ESVD and ACVD.

Antiemesis effect and brain fMRI response of gastric electrical stimulation with different parameters in dogs.

PubMed

Yu, X; Tu, L; Lei, P; Song, J; Xu, H; Hou, X

2014-07-01

The aims of this study were to investigate the effect of gastric electrical stimulation (GES) with different parameters on emesis induced by apomorphine, and possible center mechanisms by brain functional magnetic resonance imaging (fMRI). Six dogs implanted with electrodes on gastric serosa were used in this study. Part 1: Apomorphine was injected in the control session and GES sessions. GESs with different parameters were applied in GES session. Gastric slow waves and emesis and behaviors suggestive of nausea were recorded in each session. Part 2: Each dog was anesthetized and given GESs with different parameters or sham stimulation for 15 min after baseline (5 min), respectively. The location of cerebral activation induced by GES was investigated by fMRI. Apomorphine induced emesis and behaviors suggestive of nausea, and gastric dysrhythmia. The emesis frequency in control session was 5.5 ± 0.99, and symptoms score was 22.17 ± 1.01. GES with short pulse and long pulse could not improve emesis and symptoms induced by apomorphine. The emesis frequency (4.5 ± 0.76 in short pulse and 6.33 ± 1.05 in long pulse) and symptoms scores had no significant difference compared to control session (each p > 0.05). GES with trains of short pulse reduced emesis time frequency (3.83 ± 0.7, p = 0.042 vs control) and symptoms score (p = 0.037 vs control) obviously. Brain fMRI showed that GES with short pulse and long pulse activated brain stem region, and trains of short pulse made amygdala and occipital lobe activation. Apomorphine induced emesis and gastric dysrhythmia. GES with trains of short pulses relieves emetic responses through activation of amygdala region. © 2014 John Wiley & Sons Ltd.

International Patterns of Practice in the Management of Radiation Therapy-induced Nausea and Vomiting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dennis, Kristopher; Zhang Liying; Lutz, Stephen

Purpose: To investigate international patterns of practice in the management of radiation therapy-induced nausea and vomiting (RINV). Methods and Materials: Oncologists prescribing radiation therapy in the United States, Canada, The Netherlands, Australia, New Zealand, Spain, Italy, France, Hong Kong, Singapore, Cyprus, and Israel completed a Web-based survey that was based on 6 radiation therapy-only clinical cases modeled after the minimal-, low-, moderate-, and high-emetic risk levels defined in the antiemetic guidelines of the American Society of Clinical Oncology and the Multinational Association of Supportive Care in Cancer. For each case, respondents estimated the risks of nausea and vomiting separately andmore » committed to an initial management approach. Results: In total, 1022 responses were received. Risk estimates and management decisions for the minimal- and high-risk cases varied little and were in line with guideline standards, whereas those for the low- and moderate-risk cases varied greatly. The most common initial management strategies were as follows: rescue therapy for a minimal-risk case (63% of respondents), 2 low-risk cases (56% and 80%), and 1 moderate-risk case (66%); and prophylactic therapy for a second moderate-risk case (75%) and a high-risk case (95%). The serotonin (5-HT){sub 3} receptor antagonists were the most commonly recommended prophylactic agents. On multivariate analysis, factors predictive of a decision for prophylactic or rescue therapy were risk estimates of nausea and vomiting, awareness of the American Society of Clinical Oncology antiemetic guideline, and European Society for Therapeutic Radiology and Oncology membership. Conclusions: Risk estimates and management strategies for RINV varied, especially for low- and moderate-risk radiation therapy cases. Radiation therapy-induced nausea and vomiting are under-studied treatment sequelae. New observational and translational studies are needed to allow for individual

Simultaneous determination of domperidone and Itopride in pharmaceuticals and human plasma using RP-HPLC/UV detection: Method development, validation and application of the method in in-vivo evaluation of fast dispersible tablets.

PubMed

Khan, Amjad; Iqbal, Zafar; Khadra, Ibrahim; Ahmad, Lateef; Khan, Abad; Khan, Muhammad Imran; Ullah, Zia; Ismail

2016-03-20

Domperidone and Itopride are pro-kinetic agents, regulating the gastric motility and are commonly prescribed as anti emetic drugs. In the present study a simple, rapid and sensitive RP-HPLC/UV method was developed for simultaneous determination of Domperidone and Itopride in pharmaceutical samples and human plasma, using Tenofavir as internal standard. Experimental conditions were optimized and method was validated according to the standard guidelines. Combination of water (pH 3.0) and acetonitrile (65:35 v/v) was used as mobile phase, pumped at the flow rate of 1.5 ml/min. Detector wavelength was set at 210 nm and column oven temperature was 40oC. Unlike conventional liquid-liquid extraction, simple precipitation technique was applied for drug extraction from human plasma using acetonitrile for deprotienation. The method showed adequate separation of both the analytes and best resolution was achieved using Hypersil BDS C8 column (150 mm × 4.6 mm, 5 μm). The method was quite linear in the range of 20-600 ng/ml. Recovery of the method was 92.31% and 89.82% for Domperidone and Itopride, respectively. Retention time of both the analytes and internal standard was below 15 min. The lower limit of detection (LLOD) and lower limit of quantification (LLOQ) for Domperidone were 5 and 10 ng/ml while for Itopride was 12 and 15 ng/ml, respectively. The developed method was successfully applied for in-vivo analysis of fast dispersible tablets of Domperidone in healthy human volunteer. The proposed method was a part of formulation development study and was efficiently applied for determination of the two drugs in various pharmaceutical products and human plasma. Copyright © 2015 Elsevier B.V. All rights reserved.

Review article: clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics.

PubMed

Tonini, M; Cipollina, L; Poluzzi, E; Crema, F; Corazza, G R; De Ponti, F

2004-02-15

Antidopaminergic gastrointestinal prokinetics (bromopride, clebopride, domperidone, levosulpiride and metoclopramide) have been exploited clinically for the management of motor disorders of the upper gastrointestinal tract, including functional dyspepsia, gastric stasis of various origins and emesis. The prokinetic effect of these drugs is mediated through the blockade of enteric (neuronal and muscular) inhibitory D2 receptors. The pharmacological profiles of the marketed compounds differ in terms of their molecular structure, affinity at D2 receptors, ability to interact with other receptor systems [5-hydroxytryptamine-3 (5-HT3) and 5-HT4 receptors for metoclopramide; 5-HT4 receptors for levosulpiride) and ability to permeate the blood-brain barrier (compared with the other compounds, domperidone does not easily cross the barrier). It has been suggested that the serotonergic (5-HT4) component of some antidopaminergic prokinetics may enhance their therapeutic efficacy in gastrointestinal disorders, such as functional dyspepsia and diabetic gastroparesis. The antagonism of central D2 receptors may lead to both therapeutic (e.g. anti-emetic effect due to D2 receptor blockade in the area postrema) and adverse (including hyperprolactinaemia and extrapyramidal dystonic reactions) effects. As the pituitary (as well as the area postrema) is outside the blood-brain barrier, hyperprolactinaemia is a side-effect occurring with all antidopaminergic prokinetics, although to different extents. Extrapyramidal reactions are most commonly observed with compounds crossing the blood-brain barrier, although with some differences amongst the various agents. Prokinetics with a high dissociation constant compared with that of dopamine at the D2 receptor (i.e. compounds that bind loosely to D2 receptors in the nigrostriatal pathway) elicit fewer extrapyramidal signs and symptoms. A knowledge of central and peripheral D2 receptor pharmacology can help the clinician to choose between the

Systemic Lupus Erythematosus Pancreatitis: An Uncommon Presentation of a Common Disease

PubMed Central

Rodriguez, Eduardo A.; Sussman, Daniel A.; Rodriguez, Vanessa R.

2014-01-01

Patient: Female, 21 Final Diagnosis: Systemic lupus erythematosus pancreatitis Symptoms: Abdominal pain Medication: — Clinical Procedure: — Specialty: Gastroenterology and Hepatology Objective: Challenging differential diagnosis Background: Acute pancreatitis is uncommon in systemic lupus erythematosus (SLE). When recognized early and properly treated with IV steroids and hydration, the course may be benign, as exemplified in the following report. Case Report: A 21-year-old woman with history of SLE and stage IV lupus nephritis, was admitted to the Sergio Bernales Hospital ICU (Lima, Peru), complaining of worsening epigastric pain radiating to the back, and nausea and vomiting for 1 week. She denied prior cholelithiasis, alcohol use, or recent medication changes. On examination, she was tachycardic and normotensive, with a slightly distended abdomen and epigastric tenderness on deep palpation, without signs of peritoneal irritation. Laboratory results demonstrated leukocytosis without left shift, creatinine of 2.26 mg/dL, amylase of 750 U/L, and lipase of 1038 U/L. Liver chemistries, calcium, lactic acid, triglycerides, and IgG4 were normal and alcohol level was undetectable. Ultrasound did not show cholelithiasis, biliary sludge, or common bile duct dilation. CT of the abdomen showed pancreas head (parenchyma) stranding with uniform enhancement consistent with interstitial pancreatitis. Despite receiving IV fluids, opiates, anti-emetics, and nothing by mouth, her clinical condition deteriorated, prompting the use of IV methylprednisolone. After completing 1 week of IV steroids, she was transferred to the medical floor clinically improved. The patient was discharged with an oral steroid taper and complete resolution of symptoms. Conclusions: After ruling out common causes, such as hepatobiliary pathology or toxin-related insults like alcohol, hypercalcemia, hypertriglyceridemia or medications, steroids may be used in SLE pancreatitis because they might improve

Management of acute gastroenteritis in healthy children in Lebanon - A national survey.

PubMed

Alameddine, Aouni; Mourad, Sawsan; Rifai, Nahida

2010-11-01

Acute gastroenteritis remains a common condition among infants and children throughout the world. In 1996, The American Academy of Pediatrics (AAP) revised its recommendations for the treatment of infants and children with acute gastroenteritis. The purpose of this survey was to determine how closely current treatment among Lebanese pediatricians compares with the AAP recommendations and to determine the impact of such management on the healthcare system. The outline of the study was based on a telephone questionnaire that addressed the management of healthy infants and children below five years of age with acute gastroenteritis complicated by mild to moderate dehydration. In addition, the costs of medical treatment and requested laboratory studies were calculated. A total of 238 pediatricians completed the questionnaire. Most pediatricians prescribed Oral Rehydration Solutions (ORS) for rehydration (92.4%), advised breastfeeding during acute gastroenteritis (81.5%), and avoided parenteral rehydration for mild to moderate dehydration (89.1%). In addition to ORS, oral fluids such as soda, juices, and rice water were allowed for rehydration by 43.7% of pediatricians. Thirty-one percent of pediatricians delayed re-feeding for more than 6 hours after initiation of rehydration. Only 32.8% of pediatricians kept their patients on regular full-strength formulas, and only 21.8% permitted full-calorie meals for their patients. 75.4% of pediatricians did not order any laboratory studies in cases of mild dehydration and 50.4% did not order any laboratory studies for moderate dehydration. Stool analysis and culture were ordered by almost half of the pediatricians surveyed. Seventy-seven percent prescribed anti-emetics, 61% prescribed probiotics, 26.3% prescribed antibiotics systematically and local antiseptic agents, 16.9% prescribed zinc supplements, and 11% percent prescribed antidiarrheal agents. Pediatricians in Lebanon are aware of the importance of ORS and the positive

Inhibition of monoacylglycerol lipase attenuates vomiting in Suncus murinus and 2-arachidonoyl glycerol attenuates nausea in rats.

PubMed

Sticht, Martin A; Long, Jonathan Z; Rock, Erin M; Limebeer, Cheryl L; Mechoulam, Raphael; Cravatt, Benjamin F; Parker, Linda A

2012-04-01

To evaluate the role of 2-arachidonoyl glycerol (2AG) in the regulation of nausea and vomiting using animal models of vomiting and of nausea-like behaviour (conditioned gaping). Vomiting was assessed in shrews (Suncus murinus), pretreated with JZL184, a selective monoacylglycerol lipase (MAGL) inhibitor which elevates endogenous 2AG levels, 1 h before administering the emetogenic compound, LiCl. Regulation of nausea-like behaviour in rats by exogenous 2AG or its metabolite arachidonic acid (AA) was assessed, using the conditioned gaping model. The role of cannabinoid CB(1) receptors, CB(2) receptors and cyclooxygenase (COX) inhibition in suppression of vomiting or nausea-like behaviour was assessed. JZL184 dose-dependently suppressed vomiting in shrews, an effect prevented by pretreatment with the CB(1) receptor inverse agonist/antagonist, AM251. In shrew brain tissue, JZL184 inhibited MAGL activity in vivo. In rats, 2AG suppressed LiCl-induced conditioned gaping but this effect was not prevented by AM251 or the CB(2) receptor antagonist, AM630. Instead, the COX inhibitor, indomethacin, prevented suppression of conditioned gaping by 2AG or AA. However, when rats were pretreated with a high dose of JZL184 (40 mg·kg(-1) ), suppression of gaping by 2AG was partially reversed by AM251. Suppression of conditioned gaping was not due to interference with learning because the same dose of 2AG did not modify the strength of conditioned freezing to a shock-paired tone. Our results suggest that manipulations that elevate 2AG may have anti-emetic or anti-nausea potential. This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation

PubMed Central

Bolognini, D; Rock, EM; Cluny, NL; Cascio, MG; Limebeer, CL; Duncan, M; Stott, CG; Javid, FA; Parker, LA; Pertwee, RG

2013-01-01

Background and Purpose To evaluate the ability of cannabidiolic acid (CBDA) to reduce nausea and vomiting and enhance 5-HT1A receptor activation in animal models. Experimental Approach We investigated the effect of CBDA on (i) lithium chloride (LiCl)-induced conditioned gaping to a flavour (nausea-induced behaviour) or a context (model of anticipatory nausea) in rats; (ii) saccharin palatability in rats; (iii) motion-, LiCl- or cisplatin-induced vomiting in house musk shrews (Suncus murinus); and (iv) rat brainstem 5-HT1A receptor activation by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and mouse whole brain CB1 receptor activation by CP55940, using [35S]GTPγS-binding assays. Key Results In shrews, CBDA (0.1 and/or 0.5 mg·kg−1 i.p.) reduced toxin- and motion-induced vomiting, and increased the onset latency of the first motion-induced emetic episode. In rats, CBDA (0.01 and 0.1 mg·kg−1 i.p.) suppressed LiCl- and context-induced conditioned gaping, effects that were blocked by the 5-HT1A receptor antagonist, WAY100635 (0.1 mg·kg−1 i.p.), and, at 0.01 mg·kg−1 i.p., enhanced saccharin palatability. CBDA-induced suppression of LiCl-induced conditioned gaping was unaffected by the CB1 receptor antagonist, SR141716A (1 mg·kg−1 i.p.). In vitro, CBDA (0.1–100 nM) increased the Emax of 8-OH-DPAT. Conclusions and Implications Compared with cannabidiol, CBDA displays significantly greater potency at inhibiting vomiting in shrews and nausea in rats, and at enhancing 5-HT1A receptor activation, an action that accounts for its ability to attenuate conditioned gaping in rats. Consequently, CBDA shows promise as a treatment for nausea and vomiting, including anticipatory nausea for which no specific therapy is currently available. PMID:23121618

The acute gastrointestinal subsyndrome of the acute radiation syndrome: a rhesus macaque model.

PubMed

MacVittie, Thomas J; Farese, Ann M; Bennett, Alexander; Gelfond, Daniel; Shea-Donohue, Terez; Tudor, Gregory; Booth, Catherine; McFarland, Emylee; Jackson, William

2012-10-01

The development of medical countermeasures against the acute gastrointestinal subsyndrome of the acute radiation syndrome in humans requires well characterized and validated animal models. These models must adhere to the criteria of the U.S. Food and Drug Administration's Animal Rule and consider the natural history and clinical context of the human radiation response and treatment in the nuclear terrorist scenario. The models must define the radiation dose- and time-dependent relationships for mortality and major signs of morbidity, including concurrent damage in other organs, such as the bone marrow, that may contribute to the overall mortality and morbidity. There are no such models of the gastrointestinal syndrome in response to total-body irradiation in the nonhuman primate. Herein, these parameters are defined for the rhesus macaque exposed to potentially lethal doses of radiation and administered medical management. Rhesus macaques (n = 69) were exposed bilaterally to 6 MV linear accelerator-derived photon total body irradiation to midline tissue (thorax) doses ranging from 10.0 to 14.0 Gy at 0.80 Gy min(-1). Following irradiation, all animals were administered supportive care consisting of fluids, anti-emetics, anti-diarrheal medication, antibiotics, blood transfusions, analgesics, and nutrition. The primary endpoint was survival at 15 d post-irradiation. Secondary endpoints included indices of dehydration, diarrhea, weight loss, hematological parameters, cellular histology of the small and large intestine, and mean survival time of decedents. Mortality within the 15-d in vivo study defined the acute gastrointestinal syndrome and provided an LD30/15 of 10.76 Gy, LD50/15 of 11.33 Gy, and an LD70/15 of 11.90 Gy. Intestinal crypt and villus loss were dose- and time-dependent with an apparent nadir 7 d post-irradiation and recovery noted thereafter. Severe myelosuppression and thrombocytopenia were noted in all animals, requiring the administration of

The value of integrating pre-clinical data to predict nausea and vomiting risk in humans as illustrated by AZD3514, a novel androgen receptor modulator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grant, Claire, E-mail: claire.grant@astrazeneca.com; Ewart, Lorna; Muthas, Daniel

Nausea and vomiting are components of a complex mechanism that signals food avoidance and protection of the body against the absorption of ingested toxins. This response can also be triggered by pharmaceuticals. Predicting clinical nausea and vomiting liability for pharmaceutical agents based on pre-clinical data can be problematic as no single animal model is a universal predictor. Moreover, efforts to improve models are hampered by the lack of translational animal and human data in the public domain. AZD3514 is a novel, orally-administered compound that inhibits androgen receptor signaling and down-regulates androgen receptor expression. Here we have explored the utility ofmore » integrating data from several pre-clinical models to predict nausea and vomiting in the clinic. Single and repeat doses of AZD3514 resulted in emesis, salivation and gastrointestinal disturbances in the dog, and inhibited gastric emptying in rats after a single dose. AZD3514, at clinically relevant exposures, induced dose-responsive “pica” behaviour in rats after single and multiple daily doses, and induced retching and vomiting behaviour in ferrets after a single dose. We compare these data with the clinical manifestation of nausea and vomiting encountered in patients with castration-resistant prostate cancer receiving AZD3514. Our data reveal a striking relationship between the pre-clinical observations described and the experience of nausea and vomiting in the clinic. In conclusion, the emetic nature of AZD3514 was predicted across a range of pre-clinical models, and the approach presented provides a valuable framework for predicition of clinical nausea and vomiting. - Highlights: • Integrated pre-clinical data can be used to predict clinical nausea and vomiting. • Data integrated from standard toxicology studies is sufficient to make a prediction. • The use of the nausea algorithm developed by Parkinson (2012) aids the prediction. • Additional pre-clinical studies can

Can ginger ameliorate chemotherapy-induced nausea? Protocol of a randomized double blind, placebo-controlled trial.

PubMed

Marx, Wolfgang; McCarthy, Alexandra L; Ried, Karin; Vitetta, Luis; McKavanagh, Daniel; Thomson, Damien; Sali, Avni; Isenring, Liz

2014-04-09

Preliminary research shows ginger may be an effective adjuvant treatment for chemotherapy-induced nausea and vomiting but significant limitations need to be addressed before recommendations for clinical practice can be made. In a double-blinded randomised-controlled trial, chemotherapy-naïve patients will be randomly allocated to receive either 1.2 g of a standardised ginger extract or placebo per day. The study medication will be administrated as an adjuvant treatment to standard anti-emetic therapy and will be divided into four capsules per day, to be consumed approximately every 4 hours (300 mg per capsule administered q.i.d) for five days during the first three cycles of chemotherapy. Acute, delayed, and anticipatory symptoms of nausea and vomiting will be assessed over this time frame using a valid and reliable questionnaire, with nausea symptoms being the primary outcome. Quality of life, nutritional status, adverse effects, patient adherence, cancer-related fatigue, and CINV-specific prognostic factors will also be assessed. Previous trials in this area have noted limitations. These include the inconsistent use of standardized ginger formulations and valid questionnaires, lack of control for anticipatory nausea and prognostic factors that may influence individual CINV response, and the use of suboptimal dosing regimens. This trial is the first to address these issues by incorporating multiple unique additions to the study design including controlling for CINV-specific prognostic factors by recruiting only chemotherapy-naïve patients, implementing a dosing schedule consistent with the pharmacokinetics of oral ginger supplements, and independently analysing ginger supplements before and after recruitment to ensure potency. Our trial will also be the first to assess the effect of ginger supplementation on cancer-related fatigue and nutritional status. Chemotherapy-induced nausea and vomiting are distressing symptoms experienced by oncology patients; this

Further investigation of the effects of 5-hydroxytryptamine, 8-OH-DPAT and DOI to mediate contraction and relaxation responses in the intestine and emesis in Suncus murinus.

PubMed

Javid, Farideh A; Afshin-Javid, Saeed; Horn, Charles C

2018-02-15

5-HT receptors are implicated in many gastrointestinal disorders. However, the precise role of 5-HT in mediating GI responses in Suncus murnius is still unclear. Therefore in this study, the effects of 5-HT and its agonists were investigated in Suncus. The involvement of 5-HT 2C receptors in mediating emesis was also investigated. The ability of 5-HT and its agonists/antagonists at 5-HT 1A and 5-HT 2 to modify GI motility was investigated in vitro and in vivo. WAY100635 (a 5-HT 1A antagonist) inhibited the contraction response to 5-HT in the proximal segments without affecting the maximum response; whilst enhancing the contraction to 5-HT (>30.0nM) in the distal intestine. The selective 5-HT 2A and 5-HT 2B receptor antagonists MDL-100907 and RS-127445 attenuated 5-HT-induced contractions (<10.0µM) in the distal segments. RS-127445 also attenuated 5-HT-induced contractions in the central segments. The selective 5-HT 2C receptor antagonist SB-242084, attenuated the responses to 5-HT (> 3.0nM) in the proximal and central but not the distal regions. 8-OH-DPAT-induced relaxation was resistant to the antagonism by 5-HT 1A/7 antagonists. DOI in the presence of 5-HT 1A/2A/2B/2C antagonists induced greater contraction responses (>1.0µM) in most tissues, whilst RS-127445, or SB-242084, reduced the responses to DOI (< 1.0µM) in some tissues. SB-242084 also suppressed emesis-induced by motion and intragastric CuSO 4 . In conclusion, within different regions of intestine, 5-HT 2 receptors are differently involved in contraction and emetic responses and that 8-OH-DPAT induces relaxation via non-5-HT 1A/7 receptors. Suncus could provide a model to investigate these diverse actions of 5-HT. Copyright © 2018 Elsevier B.V. All rights reserved.

Emetogenicity-risk procedures in same day surgery center of an academic university hospital in United States: a retrospective cost-audit of postoperative nausea vomiting management.

PubMed

Gupta, Deepak; Haber, Halim

2014-06-01

Despite the variable results of published studies, it is imperative for ambulatory surgery centers to self-audit local cost-implications for post-operative nausea and vomiting (PONV) management. Our retrospective cost-audit assessed if there were comparative peri-anesthesia care cost-trends among patients who had undergone Low-Emetogenicity-Risk Procedures (LERP), Moderate-Emetogenicity-Risk Procedures (MERP) and Severe-Emetogenicity-Risk Procedures (SERP). This study was a review of Same Day Surgery Center practices in an academic university hospital setting during a three-year period (2010-2012). The patient lists were accessed from CIS and CITRIX App Bar for time audit and OR (operating room) schedule reports. Subsequently, OR pharmacy department ran a search for peri-operative anti-emetics and opioids that were billed for the patients at Same Day Surgery Center for the review period. The primary outcomes were the comparative costs/charges of these medications and comparative durations/ charges for these patients' stay in the post-anesthesia care unit (PACU). Secondary outcomes analyzed in the study included peri-anesthesia durations. A total of 8,657 patient records were analyzed. Almost all analyzed variables revealed statistically significant inter-variable positive correlations. The patients' age was significantly (P < 0.001) different among LERP/MERP/SERP patients (LERP: 48.8 +/- 14.7 years; MERP: 61.8 +/- 14.6 years; SERP: 51.3 +/- 14.5 years). In regards to primary and secondary outcomes, the statistical significant differences among LERP/MERP/SERP patients (after correcting for both patients' age as well as patients' sex) were only achieved for preoperative times (P = 0.002; Power = 0.9), operating room recovery times (P = 0.003; Power = 0.9), PACU stay times (P < 0.001; Power = 1.0), and PACU charges (P < 0.001; Power = 1.0). PACU stay times and PACU charges were significantly higher in patients who had undergone SERP as compared to patients who had

Inhibition of monoacylglycerol lipase attenuates vomiting in Suncus murinus and 2-arachidonoyl glycerol attenuates nausea in rats

PubMed Central

Sticht, Martin A; Long, Jonathan Z; Rock, Erin M; Limebeer, Cheryl L; Mechoulam, Raphael; Cravatt, Benjamin F; Parker, Linda A

2012-01-01

BACKGROUND AND PURPOSE To evaluate the role of 2-arachidonoyl glycerol (2AG) in the regulation of nausea and vomiting using animal models of vomiting and of nausea-like behaviour (conditioned gaping). EXPERIMENTAL APPROACH Vomiting was assessed in shrews (Suncus murinus), pretreated with JZL184, a selective monoacylglycerol lipase (MAGL) inhibitor which elevates endogenous 2AG levels, 1 h before administering the emetogenic compound, LiCl. Regulation of nausea-like behaviour in rats by exogenous 2AG or its metabolite arachidonic acid (AA) was assessed, using the conditioned gaping model. The role of cannabinoid CB1 receptors, CB2 receptors and cyclooxygenase (COX) inhibition in suppression of vomiting or nausea-like behaviour was assessed. KEY RESULTS JZL184 dose-dependently suppressed vomiting in shrews, an effect prevented by pretreatment with the CB1 receptor inverse agonist/antagonist, AM251. In shrew brain tissue, JZL184 inhibited MAGL activity in vivo. In rats, 2AG suppressed LiCl-induced conditioned gaping but this effect was not prevented by AM251 or the CB2 receptor antagonist, AM630. Instead, the COX inhibitor, indomethacin, prevented suppression of conditioned gaping by 2AG or AA. However, when rats were pretreated with a high dose of JZL184 (40 mg·kg−1), suppression of gaping by 2AG was partially reversed by AM251. Suppression of conditioned gaping was not due to interference with learning because the same dose of 2AG did not modify the strength of conditioned freezing to a shock-paired tone. CONCLUSIONS AND IMPLICATIONS Our results suggest that manipulations that elevate 2AG may have anti-emetic or anti-nausea potential. LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7 PMID:21470205

Efficacy of oral palonosetron compared to intravenous palonosetron for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: a phase 3 trial.

PubMed

Boccia, Ralph; Grunberg, Steven; Franco-Gonzales, Edwin; Rubenstein, Edward; Voisin, Daniel

2013-05-01

Palonosetron (Aloxi(®), Onicit(®)) is a pharmacologically unique 5-HT3 receptor antagonist (RA) approved as a single IV injection for the prevention of nausea and vomiting induced by chemotherapy (CINV) of either moderate or highly emetogenic potential (MEC and HEC, respectively). An oral palonosetron formulation has been developed and compared to the IV formulation. In this multinational, multicenter, double-blind, double-dummy, dose-ranging trial, 651 patients were randomly assigned to receive one of the following as a single dose prior to moderately emetogenic chemotherapy: oral palonosetron 0.25, 0.50, and 0.75 mg or IV palonosetron 0.25 mg. Patients were also randomized (1:1) to receive dexamethasone 8 mg IV or matched placebo on day 1. The primary endpoint was complete response (CR; no emesis, no rescue therapy) during the acute phase (0-24 h). Acute CR rates were 73.5, 76.3, 74.1, and 70.4 % for all patients receiving the palonosetron 0.25, 0.50, and 0.75 mg oral doses, and for IV palonosetron 0.25 mg, respectively; delayed CR (24-120 h) rates were 59.4, 62.5, 60.1, and 65.4 %, and overall CR (0-120 h) rates were 53.5, 58.8, 53.2, and 59.3 %, respectively. The addition of dexamethasone improved emetic control (acute CR rate) by at least 15 % for all groups except oral palonosetron 0.25 mg, where the acute CR improvement was approximately 7 %. Adverse events were similar in nature, incidence, and intensity for all oral and IV palonosetron groups, and were the expected adverse events for 5-HT3 RAs (primarily headache and constipation). Oral palonosetron has a similar efficacy and safety profile as IV palonosetron 0.25 mg and may be the preferred formulation in certain clinical situations. Among the tested oral treatments, a palonosetron 0.50-mg oral dose has been favored for the prevention of CINV in patients receiving moderately emetogenic chemotherapy due to a numerical gain in efficacy without a side effect disadvantage.

NEPA, a new fixed combination of netupitant and palonosetron, is a cost-effective intervention for the prevention of chemotherapy-induced nausea and vomiting in the UK

PubMed Central

Cawston, Helene; Bourhis, Francois; Eriksson, Jennifer; Ruffo, Pierfrancesco; D’Agostino, Paolo; Turini, Marco; Schwartzberg, Lee; McGuire, Alistair

2017-01-01

Background The objective was to evaluate the cost-effectiveness of NEPA, an oral fixed combination netupitant (NETU, 300 mg) and palonosetron (PA, 0.5 mg) compared with aprepitant and palonosetron (APPA) or palonosetron (PA) alone, to prevent chemotherapy-induced nausea and vomiting (CINV) in patients undergoing treatment with highly or moderately emetogenic chemotherapy (HEC or MEC) in the UK. Scope A systematic literature review and meta-analysis were undertaken to compare NEPA with currently recommended anti-emetics. Relative effectiveness was estimated over the acute (day 1) and overall treatment (days 1–5) phases, taking complete response (CR, no emesis and no rescue medication) and complete protection (CP, CR and no more than mild nausea [VAS scale <25 mm]) as primary efficacy outcomes. A three-health-state Markov cohort model, including CP, CR and incomplete response (no CR) for HEC and MEC, was constructed. A five-day time horizon and UK NHS perspective were adopted. Transition probabilities were obtained by combining the response rates of CR and CP from NEPA trials and odds ratios from the meta-analysis. Utilities of 0.90, 0.70 and 0.24 were defined for CP, CR and incomplete response, respectively. Costs included medications and management of CINV-related events and were obtained from the British National Formulary and NHS Reference Costs. The expected budgetary impact of NEPA was also evaluated. Findings In HEC patients, the NEPA strategy was more effective than APPA (quality-adjusted life days [QALDs] of 4.263 versus 4.053; incremental emesis-free and CINV-free days of +0.354 and +0.237, respectively) and was less costly (£80 versus £124), resulting in NEPA being the dominant strategy. In MEC patients, NEPA was cost effective, cumulating in an estimated 0.182 extra QALDs at an incremental cost of £6.65 compared with PA. Conclusion Despite study limitations (study setting, time horizon, utility measure), the results suggest NEPA is cost effective

Can ginger ameliorate chemotherapy-induced nausea? Protocol of a randomized double blind, placebo-controlled trial

PubMed Central

2014-01-01

Background Preliminary research shows ginger may be an effective adjuvant treatment for chemotherapy-induced nausea and vomiting but significant limitations need to be addressed before recommendations for clinical practice can be made. Methods/Design In a double–blinded randomised-controlled trial, chemotherapy-naïve patients will be randomly allocated to receive either 1.2 g of a standardised ginger extract or placebo per day. The study medication will be administrated as an adjuvant treatment to standard anti-emetic therapy and will be divided into four capsules per day, to be consumed approximately every 4 hours (300 mg per capsule administered q.i.d) for five days during the first three cycles of chemotherapy. Acute, delayed, and anticipatory symptoms of nausea and vomiting will be assessed over this time frame using a valid and reliable questionnaire, with nausea symptoms being the primary outcome. Quality of life, nutritional status, adverse effects, patient adherence, cancer-related fatigue, and CINV-specific prognostic factors will also be assessed. Discussion Previous trials in this area have noted limitations. These include the inconsistent use of standardized ginger formulations and valid questionnaires, lack of control for anticipatory nausea and prognostic factors that may influence individual CINV response, and the use of suboptimal dosing regimens. This trial is the first to address these issues by incorporating multiple unique additions to the study design including controlling for CINV-specific prognostic factors by recruiting only chemotherapy-naïve patients, implementing a dosing schedule consistent with the pharmacokinetics of oral ginger supplements, and independently analysing ginger supplements before and after recruitment to ensure potency. Our trial will also be the first to assess the effect of ginger supplementation on cancer-related fatigue and nutritional status. Chemotherapy-induced nausea and vomiting are distressing symptoms

[Comparison of antiemesis effects of granisetron, aprepitant and dexamethasone to palonosetron, aprepitant and dexamethasone in treatment of high-emetic risk chemotherapy-induced nausea and vomiting - a retrospective study for efficacy and safety in a single institute].

PubMed

Osawa, Hiroshi; Goto, Hiroaki; Myojo, Tomohiro

2013-05-01

Nausea and vomiting are among the most problematic symptoms experienced by patients with cancer who are receiving chemotherapy. 5-hydroxytryptamine 3(5-HT3)-receptor antagonists, NK1 receptor antagonists(aprepitant)and dexamethasone are now the standard therapies for preventing chemotherapy-induced nausea and vomiting(CINV)that follow highly emetogenic chemotherapy, such as cisplatin and anthracycline. However, since it is not cleared which 5-HT3-recepter antagonist is a proper treatment for combined use with aprepitant and dexamethasone, we conducted a questionnaire survey, which used the numerical rating scale(NRS), for comparing palonosetron with granisetron in the same patient. Palonosetron showed a significant improvement of nausea for both acute(within 24 hours)and delayed phase(24-120 hours later), regardless of the type of chemotherapy(cisplatin or anthracycline-based regimen). Furthermore, palonosetron had a tolerable safety profile. Our study suggests that palonosetron-based antiemetic treatment will be a preferred choice for preventing CINV following highly emetogenic chemotherapy.

Transdermal granisetron versus palonosetron for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: a multicenter, randomized, open-label, cross-over, active-controlled, and phase IV study.

PubMed

Seol, Young Mi; Kim, Hyo Jeong; Choi, Young Jin; Lee, Eun Mi; Kim, Yang Soo; Oh, Sung Yong; Koh, Su Jin; Baek, Jin Ho; Lee, Won Sik; Joo, Young Don; Lee, Hyun Gi; Yun, Eun Young; Chung, Joo Seop

2016-02-01

Palonosetron is the second-generation 5-hydroxytryptamine 3 receptor antagonist (5-HT3RA) that has shown better efficacy than the first-generation 5-HT3RA for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC). Granisetron transdermal delivery system (GTDS), a novel transdermal formulation, was developed to deliver granisetron continuously over 7 days. This study compared the efficacy and tolerability of the GTDS to palonosetron for the control of CINV following MEC. A total of 196 patients were randomized to GP or PG group. In this multicenter, randomized, open-label, cross-over, active-controlled, Phase IV study, GP group was assigned to receive transdermal granisetron (one GTDS patch, 7 days) in the first chemotherapy cycle, palonosetron (iv 0.25 mg/day, 1 days) in the second chemotherapy cycle before receiving MEC, and PG group was assigned to receive palonosetron in the first cycle and GTDS in the second cycle. Primary endpoint was the percentage of chemotherapy cycles achieving complete response (CR; defined as no emetic episodes and no rescue medication use) during the acute phase (0-24 h in post-chemotherapy; non-inferiority comparison with palonosetron). Total 333 cycles (165 in GTDS and 168 in palonosetron) were included in the per protocol analysis. The GTDS cycles showed non-inferiority to palonosetron cycles during the acute phase: CR was achieved by 124 (75.2 %) patients in the GTDS cycles and 134 (79.8 %) patients in the palonosetron cycles (treatment difference, -4.6 %; 95 % confidence interval, -13.6-4.4). There was no significant difference in CR rate during acute phase after the end of the first and second chemotherapy cycle between GP and PG group (p = 0.405, p = 0.074). Patients' satisfaction, assessed using Functional Living Index-Emesis (FLI-E), GTDS cycle were higher than those of palonosetron cycle in GP group (FLI-E score; median 1549.5 in GTDS cycle, median 1670

Safety of serotonin (5-HT3) receptor antagonists in patients undergoing surgery and chemotherapy: protocol for a systematic review and network meta-analysis.

PubMed

Tricco, Andrea C; Soobiah, Charlene; Antony, Jesmin; Hemmelgarn, Brenda; Moher, David; Hutton, Brian; Straus, Sharon E

2013-06-28

Serotonin (5-HT3) receptor antagonists are a class of antiemetic medications often used to prevent nausea and vomiting among patients undergoing chemotherapy, radiotherapy or surgery. However, recent studies suggest that these agents might be associated with increased cardiac harm. To examine this further, we are proposing to conduct a systematic review and network meta-analysis on the comparative safety of 5-HT3 receptor antagonists among patients undergoing chemotherapy or surgery. Studies reporting one or more safety outcomes of interest for 5-HT3 receptor antagonists compared with each other, placebo, and/or other anti-emetic agents (for example, benzamides, phenothiazines, butyrophenones, antihistamines, and anticholinergics) among children and adult patients undergoing surgery or chemotherapy will be included. Our primary outcome of interest is arrhythmia. Our secondary outcomes include cardiac death, QT prolongation, PR prolongation, all-cause mortality, nausea, and vomiting. We will include experimental studies, quasi-experimental studies (namely controlled before-after and interrupted time series), and observational studies (namely cohort studies). We will not limit inclusion by publication status, time period, duration of follow-up or language of dissemination.Electronic databases (for example, MEDLINE, EMBASE) will be searched from inception onwards. These main searches will be supplemented by searching for difficult to locate and unpublished studies, such as dissertations, and governmental reports. The eligibility criteria will be pilot-tested and subsequently used to screen the literature search results by two reviewers in duplicate. A similar process will be followed for full-text screening, data abstraction, and risk of bias/methodological quality appraisal. The Cochrane Risk of Bias tool will be used to appraise experimental and quasi-experimental studies, and cohort studies will be assessed using the Newcastle Ottawa Scale. If the data allows

Prophylaxis of Radiation-Induced Nausea and Vomiting Using 5-Hydroxytryptamine-3 Serotonin Receptor Antagonists: A Systematic Review of Randomized Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salvo, Nadia; Doble, Brett; Khan, Luluel

Purpose: To systematically review the effectiveness and safety of 5-hydroxytryptamine-3 receptor antagonists (5-HT3 RAs) compared with other antiemetic medication or placebo for prophylaxis of radiation-induced nausea and vomiting. Methods and Materials: We searched the following electronic databases: MEDLINE, Embase, the Cochrane Central Register of Controlled Clinical Trials, and Web of Science. We also hand-searched reference lists of included studies. Randomized, controlled trials that compared a 5-HT3 RA with another antiemetic medication or placebo for preventing radiation-induced nausea and vomiting were included. We excluded studies recruiting patients receiving concomitant chemotherapy. When appropriate, meta-analysis was conducted using Review Manager (v5) software. Relativemore » risks were calculated using inverse variance as the statistical method under a random-effects model. We assessed the quality of evidence by outcome using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results: Eligibility screening of 47 articles resulted in 9 included in the review. The overall methodologic quality was moderate. Meta-analysis of 5-HT3 RAs vs. placebo showed significant benefit for 5-HT3 RAs (relative risk [RR] 0.70; 95% confidence interval [CI] 0.57-0.86 for emesis; RR 0.84, 95% CI 0.73-0.96 for nausea). Meta-analysis comparing 5-HT3 RAs vs. metoclopramide showed a significant benefit of the 5-HT3 RAs for emetic control (RR 0.27, 95% CI 0.15-0.47). Conclusion: 5-Hydroxytryptamine-3 RAs are superior to placebo and other antiemetics for prevention of emesis, but little benefit was identified for nausea prevention. 5-Hydroxytryptamine-3 RAs are suggested for prevention of emesis. Limited evidence was found regarding delayed emesis, adverse events, quality of life, or need for rescue medication. Future randomized, controlled trials should evaluate different 5-HT3 antiemetics and new agents with novel mechanisms of action such at

Accidental poisoning in childhood: a multicentre survey. 2. The role of packaging in accidents involving medications.

PubMed

Wiseman, H M; Guest, K; Murray, V S; Volans, G N

1987-07-01

To assess the effectiveness of child-resistant closures (CRCs) and unit dose packaging in preventing childhood poisoning with medications, a survey by 14 hospitals of accidental suspected poisoning in children under 5-years-old, was compared with a survey of a representative sample of households with children under 5 living in the catchment areas of the hospitals. Nine hundred and thirty-eight medications thought to have been ingested by 877 children were compared with 5827 medications found in households with children. The relationship between availability of packs or medications in the home and their involvement in accidents was quantified by means of an Accident Association Index (AAI). A low AAI indicated that the involvement of a pack or medication was less than expected from availability and therefore safe. A high AAI indicated that involvement was greater than expected and therefore unsafe. Medications involved in suspected poisoning were most frequently packed in containers without CRCs (63%) or transparent blisters (20%); both had high AAIs. CRCs, strips, sachets and opaque blisters had low AAIs. Analgesics, expectorants and gastrointestinal medications, had low AAIs, while oral contraceptives, hypnotics, sedative/tranquillizers, antidepressants, anticonvulsants, anti-emetics, and anti-infectives had high AAIs. Prescription medications were more frequently involved in accidents than over-the-counter (OTC) medications and had a higher AAI. Comparison of the AAIs of different kinds of medication in each of their various pack types showed that safe packaging reduced the risk from medications which had a high average AAI. Only 40% of medications were in their normal storage place at the time of the accident. Medicine and bathroom cabinets, and kitchen cupboards and drawers were the safest places to store medications. Handbags, fridges, and shelves or ledges in the bathroom were the most unsafe places. No pack had a low AAI when stored on open shelves

Contractile effect of tachykinins on Suncus murinus (house musk shrew) isolated ileum.

PubMed

Cheng, Frankie H M; Chan, Sze Wa; Rudd, John A

2008-01-01

Recent studies used Suncus murinus to investigate the anti-emetic potential of NK(1) tachykinin receptor antagonists. However, the pharmacology of tachykinin receptors in this species has not been fully characterized. In the present studies, therefore, we examined a range of tachykinin receptor agonists for a capacity to induce contractions of the isolated ileum. The tachykinin NK1 receptor preferring agonists substance P, septide and [Sar9Met(O2)11] substance P, and the tachykinin NK2 preferring agonists neurokinin A and GR 64349 (Lys-Asp-Ser-Phe-Val-Gly-R-gamma-lactam-Leu-Met-NH2) caused concentration dependent contractions with EC50 values in the nanomolar range. However, the tachykinin NK3 preferring agonists neurokinin B and senktide (1nM-1microM) induced only weak contractions. The action of senktide, but not [Sar9Met(O2)11] substance P, septide, or GR 64349, was antagonized significantly by atropine (P<0.05); tetrodotoxin and hexamethonium were inactive. The tachykinin NK1 receptor antagonist CP-99,994 ((+)-[(2S,3S)-3-(2-methoxy-benzyl-amino)-2-phenylpiperidine]) (10-100nM) inhibited substance P- and septide-induced contractions non-competitively. The pA2 value estimated for CP-99,994 against septide was 7.3+/-0.1. It also non-competitively antagonized the contractile responses induced by [Sar9Met(O2)11] substance P with a pA2 of 7.4+/-0.1. CP-99,994 also had a slight inhibitory action on neurokinin A-induced contractions, but did not modify the action of GR 64349. Conversely, the tachykinin NK2 receptor antagonist, saredutant, competitively antagonized GR 64349-induced contractions with a pA2 of 7.34+/-0.02. On the other hand, the presence of both CP-99,994 and saredutant competitively antagonized substance P-induced contraction. The present studies indicate that tachykininNK1 and NK2 receptors exist in the ileum of S. murinus and are involved in mediating contractions directly on smooth muscle, whereas tachykinin NK3 receptors may play a minor role

A Prospective, Randomized, Double-Blinded, Double-Dummy Pilot Study to Assess the Preemptive Effect of Triple Therapy with Aprepitant, Dexamethasone, and Promethazine versus Ondansetron, Dexamethasone and Promethazine on Reducing the Incidence of Postoperative Nausea and Vomiting Experienced by Patients Undergoing Craniotomy Under General Anesthesia.

PubMed

Bergese, Sergio Daniel; Puente, Erika G; Antor, Maria A; Viloria, Adolfo L; Yildiz, Vedat; Kumar, Nicolas Alexander; Uribe, Alberto A

2016-01-01

Postoperative nausea and vomiting (PONV) is among the most common distressing complications of surgery under anesthesia. Previous studies have demonstrated that patients who undergo craniotomy have incidences of nausea and vomiting as high as 50-70%. The main purpose of this pilot study is to assess the incidence of PONV by using two different prophylactic regimens in subjects undergoing a craniotomy. Thus, we designed this study to assess the efficacy and safety of triple therapy with the combination of dexamethasone, promethazine, and aprepitant versus ondansetron to reduce the incidence of PONV in patients undergoing craniotomy. This is a prospective, single center, two-armed, randomized, double-dummy, double-blind, pilot study. Subjects were randomly assigned to one of the two treatment groups. Subjects received 40 mg of aprepitant pill (or matching placebo pill) 30-60 min before induction of anesthesia and 4 mg of ondansetron IV (or 2 ml of placebo saline solution) at induction of anesthesia. In addition, all subjects received 25 mg of promethazine IV and 10 mg of dexamethasone IV at induction of anesthesia. Assessments of PONV commenced for the first 24 h after surgery and were subsequently assessed for up to 5 days. The overall incidence of PONV during the first 24 h after surgery was 31.0% (n = 15) in the aprepitant group and 36.2% (n = 17) for the ondansetron group. The median times to first emetic and significant nausea episodes were 7.6 (2.9, 48.7) and 14.3 (4.4, 30.7) hours, respectively, for the aprepitant group and 6.0 (2.2, 29.5) and 9.6 (0.7, 35.2) hours, respectively, for the ondansetron group. There were no statistically significant differences between these groups. No adverse events directly related to study medications were found. This pilot study showed similar effectiveness when comparing the two PONV prophylaxis regimens. Our data showed that both treatments could be effective regimens to prevent PONV in patients

Falls prevention focused medication review by a pharmacist in an acute hospital: implications for future practice.

PubMed

Browne, Claire; Kingston, Claire; Keane, Claire

2014-10-01

Patients at risk of falling are regularly prescribed medicines which increase falls risk. Medication review is a widely advocated risk reduction strategy. The objectives of this descriptive study were to determine the number and types of falls risk medicines suitable for intervention, and to develop guidance to optimise the effectiveness of future medication related falls prevention initiatives. An Irish acute teaching hospital and tertiary referral centre. 50 hospital in-patients at risk of falls underwent medication review focused on falls prevention by a pharmacist. Falls risk medicines were identified, and reviewed. If scope to discontinue, dose reduce or switch to a safer alternative was identified by the pharmacist, the suggested medication changes were communicated to the patient's care team. Identification of the classes of falls risk medicines and types of prescriptions with greatest potential for intervention. Results The mean number of falls risk medicines prescribed to each patient was 4.8 (± 2.8) and the total number prescribed to the 50 patients was 238. Following medication review, the pharmacist identified 48 (20 %) as suitable for intervention. Consequently, 34 medication changes (70.8 %) were implemented. Four medication classes accounted for over 80 % of medication changes. These were anti-emetics, opioid analgesics, anti-cholinergic agents acting on the bladder and benzodiazepines/hypnotics. Intervention was statistically significantly more likely to be possible in the case of p.r.n. medicines compared to regular medicines (p < 0.001, Chi square test). Medication reviews focused on falls prevention took an average of 23.5 min per patient to complete. Medication reviews focused on falls prevention involve striking a balance between minimising medicines associated with falls and effectively treating medical conditions. We found only 20 % of falls risk medicines were suitable for change, and reviews were time consuming and resource intensive

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

PubMed

Alhadeff, Amber L; Holland, Ruby A; Nelson, Alexandra; Grill, Harvey J; De Jonghe, Bart C

2015-08-05

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. Copyright © 2015 the authors 0270-6474/15/3511094-11$15.00/0.

Evaluation of efficacy and tolerability of fixed dose combination of ofloxacin with ornidazole infusion (infusion O2) in the management of diarrhoea and dysentery.

PubMed

Faruqui, Arif A; Joshi, Chandrakant

2012-03-01

Acute diarrhoea in adults is one of the most commonly encountered medical emergency in general practice and is responsible for considerable morbidity around the world. To evaluate the efficacy and tolerability of fixed dose combination of ofloxacin with ornidazole infusion (infusion O2) in the management of diarrhoea and dysentery, a study was carried out among 290 patients, age group from 18 to 65 years suffering from diarrhoea, dysentery, gastro-enteritis. Study drug infusion O2, (Medley Pharmaceutical, Mumbai) containing ofloxacin 200 mg + ornidazole 500 mg was administrated twice daily for a duration of 5 days. Number of soft or watery stool, body temperature, nausea, abdominal pain, gas and flatulence were recorded at baseline and at the end of the study. Tolerability and efficacy was evaluated based on the global assessment by the investigator based on a 3-point scale marked as excellent/good/poor. Two hundred and fifty-six-patients (160 male and 96 female) were included for final analysis, 34 patients lost to follow-up. Mean number of watery stool per day was reduced from 9.273 +/- 0.4537 to 1.375 +/- 0.07001 (p < 0.0001) by infusion O2. Body temperature was significantly reduced from 38.055 +/- 0.045 degrees C to 36.778 +/- 0.016 degrees C (p < 0.0001) at the end of the study. Pretreatment symptom nausea was significantly reduced in 90.34% of patients. Improvement in vomiting symptoms was reported in 72.35% of patients after administration of anti-emetic drug; 96.84% and 77.25% of patients reported improvement in abdominal pain and gas/flatulence respectively at the end of the trial by infusion O2. As per investigators' assessment about efficacy of trial drug, 98.43% of patients reported good to excellent and 1.56% reported poor efficacy. As per investigators' assessment about tolerability 98.43% of patients reported good to excellent and 1.17% reported poor tolerability. Minor incidences of nausea, gastritis, metallic taste were reported in 7.42%, 7

Inhibition of emesis by tachykinin NK1 receptor antagonists in Suncus murinus (house musk shrew).

PubMed

Rudd, J A; Ngan, M P; Wai, M K

1999-02-05

The anti-emetic potential of CP-122,721 ((+)-2S,3S)-3-(2-methoxy-5-trifluoromethoxybenzyl)amino-2-phenylpi peridine), CP-99,994 ((+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine), CP-100,263 ((-)-(2R,3R)-3-(2-methoxybenzylamino)-2-phenylpiperidine), RP 67580 ((3R, 7aR)-7,7-diphenyl-2-[1-imino-2-(2-methoxyphenyl)ethyl] po-hydroisoindol-4-one), FK 888 (N2-[(4R)-4-hydroxy-1-(1-methyl-1H-in-dole-3-yl)carbonyl-L-propyl] -N-methyl-N-phenylmethyl-1-3-(2-naphthyl)-alaninamide) and GR 82334 ([D-Pro9[spiro-g-lactam]Leu10]-physalaemin-(1-11)) was investigated to inhibit nicotine (5 mg/kg, s.c.)-, copper sulphate pentahydrate (120 mg/kg, intragastric)- and motion (4 cm horizontal displacement at 1 Hz for 5 min)-induced emesis in Suncus murinus. A 30 min intraperitoneal pre-treatment with CP-122,721, CP-99,994, RP 67580 and FK 888 significantly (P < 0.05) antagonized nicotine-induced emesis with ID50 values of 2.1, 2.3, 13.5 and 19.2 mg/kg, respectively CP-100,263, the less active enantiomer of CP-99,994, was inactive at doses up to 10 mg/kg. Infusion of GR 82334, CP-122,721, CP-99,994 and FK 888 into the dorsal vagal complex of the hindbrain also antagonized nicotine-induced emesis yielding ID50 values of 1.1, 3.0, 3.3 and 58.0 microg/dorsal vagal complex, respectively RP 67580 and CP-100,263 were inactive. RP 67580 and FK 888 failed to antagonize copper sulphate-induced emesis but CP-122,721 and CP-99,994 were active yielding ID50 values of 2.2 and 3.0 mg/kg, i.p., respectively. CP-99,994 also completely prevented motion-induced emesis at 10 mg/kg, i.p. (P < 0.05) and RP 67580 produced a significant reduction of motion-induced emesis at 10 mg/kg, i.p. (P < 0.05). These studies provide evidence of a central site of action of tachykinin NK1 receptor antagonists to inhibit nicotine-induced emesis in S. murinus and confirm the broad profile of inhibitory action. The rank order of potency of the antagonists following the intra-dorsal vagal complex administration suggests

A case of severe anorexia, excessive weight loss and high peptide YY levels after sleeve gastrectomy.

PubMed

Pucci, Andrea; Cheung, Wui Hang; Jones, Jenny; Manning, Sean; Kingett, Helen; Adamo, Marco; Elkalaawy, Mohamed; Jenkinson, Andrew; Finer, Nicholas; Doyle, Jacqueline; Hashemi, Majid; Batterham, Rachel L

2015-01-01

Sleeve gastrectomy (SG) is the second most commonly performed bariatric procedure worldwide. Altered circulating gut hormones have been suggested to contribute post-operatively to appetite suppression, decreased caloric intake and weight reduction. In the present study, we report a 22-year-old woman who underwent laparoscopic SG for obesity (BMI 46 kg/m(2)). Post-operatively, she reported marked appetite reduction, which resulted in excessive weight loss (1-year post-SG: BMI 22 kg/m(2), weight loss 52%, >99th centile of 1-year percentage of weight loss from 453 SG patients). Gastrointestinal (GI) imaging, GI physiology/motility studies and endoscopy revealed no anatomical cause for her symptoms, and psychological assessments excluded an eating disorder. Despite nutritional supplements and anti-emetics, her weight loss continued (BMI 19 kg/m(2)), and she required nasogastric feeding. A random gut hormone assessment revealed high plasma peptide YY (PYY) levels. She underwent a 3 h meal study following an overnight fast to assess her subjective appetite and circulating gut hormone levels. Her fasted nausea scores were high, with low hunger, and these worsened with nutrient ingestion. Compared to ten other post-SG female patients, her fasted circulating PYY and nutrient-stimulated PYY and active glucagon-like peptide 1 (GLP1) levels were markedly elevated. Octreotide treatment was associated with suppressed circulating PYY and GLP1 levels, increased appetite, increased caloric intake and weight gain (BMI 22 kg/m(2) after 6 months). The present case highlights the value of measuring gut hormones in patients following bariatric surgery who present with anorexia and excessive weight loss and suggests that octreotide treatment can produce symptomatic relief and weight regain in this setting. Roux-en-Y gastric bypass and SG produce marked sustained weight reduction. However, there is a marked individual variability in this reduction, and post-operative weight loss

Interventions for nausea and vomiting in early pregnancy

PubMed Central

Matthews, Anne; Dowswell, Therese; Haas, David M; Doyle, Mary; O’Mathúna, Dónal P

2014-01-01

Background Nausea, retching and vomiting are very commonly experienced by women in early pregnancy. There are considerable physical and psychological effects on women who experience these symptoms. This is an update of a review of interventions for nausea and vomiting in early pregnancy previously published in 2003. Objectives To assess the effectiveness and safety of all interventions for nausea, vomiting and retching in early pregnancy, up to 20 weeks’ gestation. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (28 May 2010). Selection criteria All randomised controlled trials of any intervention for nausea, vomiting and retching in early pregnancy. We excluded trials of interventions for hyperemesis gravidarum which are covered by another review. We also excluded quasi-randomised trials and trials using a crossover design. Data collection and analysis Four review authors, in pairs, reviewed the eligibility of trials and independently evaluated the risk of bias and extracted the data for included trials. Main results Twenty-seven trials, with 4041 women, met the inclusion criteria. These trials covered many interventions, including acupressure, acustimulation, acupuncture, ginger, vitamin B6 and several antiemetic drugs. We identified no studies of dietary or other lifestyle interventions. Evidence regarding the effectiveness of P6 acupressure, auricular (ear) acupressure and acustimulation of the P6 point was limited. Acupuncture (P6 or traditional) showed no significant benefit to women in pregnancy. The use of ginger products may be helpful to women, but the evidence of effectiveness was limited and not consistent. There was only limited evidence from trials to support the use of pharmacological agents including vitamin B6, and anti-emetic drugs to relieve mild or moderate nausea and vomiting. There was little information on maternal and fetal adverse outcomes and on psychological, social or economic outcomes. We

Prevalence, virulence factor genes and antibiotic resistance of Bacillus cereus sensu lato isolated from dairy farms and traditional dairy products.

PubMed

Owusu-Kwarteng, James; Wuni, Alhassan; Akabanda, Fortune; Tano-Debrah, Kwaku; Jespersen, Lene

2017-03-14

B. cereus are of particular interest in food safety and public health because of their capacity to cause food spoilage and disease through the production of various toxins. The aim of this study was to determine the prevalence, virulence factor genes and antibiotic resistance profile of B. cereus sensu lato isolated from cattle grazing soils and dairy products in Ghana. A total of 114 samples made up of 25 soil collected from cattle grazing farm land, 30 raw milk, 28 nunu (yoghurt-like product) and 31 woagashie (West African soft cheese). Ninety-six B. cereus sensu lato isolates from 54 positive samples were screened by PCR for the presence of 8 enterotoxigenic genes (hblA, hblC, hblD, nheA, nheB, nheC, cytK and entFM), and one emetic gene (ces). Phenotypic resistance to 15 antibiotics were also determined for 96 B. cereus sensu lato isolates. About 72% (18 of 25 soil), 47% (14 of 30 raw milk), 35% (10 of 28 nunu) and 39% (12 of 31 woagashi) were positive for B. cereus sensu lato with mean counts (log 10 cfu/g) of 4.2 ± 1.8, 3.3 ± 2.0, 1.8 ± 1.4 and 2.6 ± 1.8 respectively. The distribution of enterotoxigenic genes revealed that 13% (12/96 isolates) harboured all three gene encoding for haemolytic enterotoxin HBL complex genes (hblA, hblC and hblD), 25% (24/96 isolates) possessed no HBL gene, whereas 63% (60/96 isolates) possessed at least one of the three HBL genes. All three genes encoding for non-haemolytic enterotoxin (nheA, nheB and nheC) were detected in 60% (57/96) isolates, 14% (13/96) harboured only one gene, 19% (18/96) whereas 8% possessed none of the NHE genes. The detection rates of cytk, entFM, and ces genes were 75, 67 and 9% respectively. Bacillus cereus s. l. isolates were generally resistant to β-lactam antibiotics such as ampicillin (98%), oxacillin (92%), penicillin (100%), amoxicillin (100%), and cefepime (100%) but susceptible to other antibiotics tested. Bacillus cereus s. l. is prevalent in soil, raw milk and dairy

Availability of medicines in public sector health facilities of two North Indian States.

PubMed

Prinja, Shankar; Bahuguna, Pankaj; Tripathy, Jaya Prasad; Kumar, Rajesh

2015-12-23

Access to free essential medicines is a critical component of universal health coverage. However availability of essential medicines is poor in India with more than two-third of the people having limited or no access. This has pushed up private out-of-pocket expenditure due to medicines. The states of Punjab and Haryana are in the process of institutionalizing drug procurement models to provide uninterrupted access to essential medicines free of cost in all public hospitals and health centres. We undertook this study to assess the availability of medicines in public sector health facilities in the 2 states. Secondly, we also ascertained the quality of storage and inventory management systems in health facilities. The present study was carried out in 80 public health facilities across 12 districts in Haryana and Punjab states. Overall, within each state 1 MC, 6 DHs, 11 CHCs and 22 PHCs were selected for the study. Drug procurement mechanisms in both the states were studied through document reviews and in-depth interviews with key stakeholders. Stock registers were reviewed to collect data on availability of a basket of essential medicines -92 at Primary Health Centre (PHC) level, 132 at Community Health Centre (CHC) level and 160 at tertiary care (District Hospital/Medical College) level. These essential medicines were selected based on the Essential Medicine List (EML) of the Department of Health (DOH). Overall availability of medicines was 45.2% and 51.1% in Punjab and Haryana respectively. Availability of anti-hypertensives was around 60% in both the states whereas for anti-diabetics it was 44% and 47% in Punjab and Haryana respectively. Atleast one drug in each of the categories including analgesic/antipyretic, anti-helminthic, anti-spasmodic, anti-emetic, anti-hypertensive and uterotonics were nearly universally available in public sector facilities. On the contrary, medicines such as thrombolytics, anti-cancer and endocrine medicines were available in less

The Effect of a Combination Treatment Using Palonosetron, Promethazine, and Dexamethasone on the Prophylaxis of Postoperative Nausea and Vomiting and QTc Interval Duration in Patients Undergoing Craniotomy under General Anesthesia: A Pilot Study.

PubMed

Bergese, Sergio D; Puente, Erika G; Antor, Maria A; Capo, Gerardo; Yildiz, Vedat O; Uribe, Alberto A

2016-01-01

Postoperative nausea and vomiting (PONV) is a displeasing experience that distresses surgical patients during the first 24 h after a surgical procedure. The incidence of postoperative nausea occurs in about 50%, the incidence of postoperative vomiting is about 30%, and in high-risk patients, the PONV rate could be as high as 80%. Therefore, the study design of this single arm, non-randomized, pilot study assessed the efficacy and safety profile of a triple therapy combination with palonosetron, dexamethasone, and promethazine to prevent PONV in patients undergoing craniotomies under general anesthesia. The research protocol was approved by the institutional review board and 40 subjects were provided written informed consent. At induction of anesthesia, a triple therapy of palonosetron 0.075 mg IV, dexamethasone 10 mg IV, and promethazine 25 mg IV was given as PONV prophylaxis. After surgery, subjects were transferred to the surgical intensive care unit or post anesthesia care unit as clinically indicated. Ondansetron 4 mg IV was administered as primary rescue medication to subjects with PONV symptoms. PONV was assessed and collected every 24 h for 5 days via direct interview and/or medical charts review. The overall incidence of PONV during the first 24 h after surgery was 30% (n = 12). The incidence of nausea and emesis 24 h after surgery was 30% (n = 12) and 7.5% (n = 3), respectively. The mean time to first emetic episode, first rescue, and first significant nausea was 31.3 (±33.6), 15.1 (±25.8), and 21.1 (±25.4) hours, respectively. The overall incidence of nausea and vomiting after 24-120 h period after surgery was 30% (n = 12). The percentage of subjects without emesis episodes over 24-120 h postoperatively was 70% (n = 28). No subjects presented a prolonged QTc interval ≥500 ms before and/or after surgery. Our data demonstrated that this triple therapy regimen may be an adequate alternative regimen for the

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

PubMed Central

Alhadeff, Amber L.; Holland, Ruby A.; Nelson, Alexandra; Grill, Harvey J.

2015-01-01

). 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. PMID:26245970

Hesperetin-5,7,3'-O-triacetate suppresses airway hyperresponsiveness in ovalbumin-sensitized and challenged mice without reversing xylazine/ketamine-induced anesthesia in normal mice.

PubMed

Yang, You-Lan; Chen, Chi-Li; Chen, Chi-Ming; Ko, Wun-Chang

2017-05-30

We recently reported that hesperetin-5,7,3'-O-triacetate (HTA) dually inhibited phosphodiesterase (PDE)3/4 with a therapeutic ratio of 20.8. The application and development of PDE4 inhibitors for treating asthma or COPD are limited by their side effects, such as nausea, vomiting and gastric hypersecretion. PDE4 inhibitors were reported to reverse xylazine/ketamine-induced anesthesia in rats and triggered vomiting in ferrets. Thus the reversing effect of HTA on xylazine/ketamine-induced anesthesia in mice was studied to assess emetic effect of HTA. The aim of this study was to prove the therapeutic effect of HTA without vomiting effect at an effective dose for treating COPD. Ten female BALB/c mice in each group were sensitized by ovalbumin (OVA) on days 0 and 14. On day 21, these mice were emphasized the sensitization by Freund's complete adjuvant. Mice were challenged by 1% OVA nebulization on days 28, 29, and 30. Airway hyperresponsiveness (AHR) was assessed on day 32 in each group, using the FlexiVent system to determine airway resistance (R L ) and lung dynamic compliance (C dyn ) in anesthetized ovalbumin (OVA)-sensitized and challenged mice. Each group was orally administered HTA (10 ~ 100 μmol/kg), roflumilast (1 and 5 mg/kg) or vehicles (controls) 2 h before and 6 and 24 h after OVA provocation. For comparison, sham-treated mice were challenged with saline instead of 1% OVA. The ability to reverse xylazine/ketamine-induced anesthesia by HTA or roflumilast for 3 h was determined in normal mice. We used roflumilast, a selective PDE4 inhibitor and bronchodilator for severe COPD approved by the US Food and Drug Administration, as a reference drug. In the results, HTA (100 μmol/kg, p.o.) or roflumilast (5 mg/kg, p.o.) significantly suppressed all R L values of MCh at 0.78 ~ 25 mg/mL and enhanced C dyn values of MCh at 3.125 ~ 25 mg/mL compared to OVA-sensitized and -challenged control mice. Orally administered 1, 3 or 10 mg/kg roflumilast

Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort.

PubMed

Baron, Eric P; Lucas, Philippe; Eades, Joshua; Hogue, Olivia

2018-05-24

patients treating with cannabis were positive for migraine. Hybrid strains were preferred in ID Migraine™, headache, and most pain groups, with "OG Shark", a high THC (Δ9-tetrahydrocannabinol)/THCA (tetrahydrocannabinolic acid), low CBD (cannabidiol)/CBDA (cannabidiolic acid), strain with predominant terpenes β-caryophyllene and β-myrcene, most preferred in the headache and ID Migraine™ groups. This could reflect the potent analgesic, anti-inflammatory, and anti-emetic properties of THC, with anti-inflammatory and analgesic properties of β-caryophyllene and β-myrcene. Opiates/opioids were most commonly substituted with cannabis. Prospective studies are needed, but results may provide early insight into optimizing crossbred cannabis strains, synergistic biochemical profiles, dosing, and patterns of use in the treatment of headache, migraine, and chronic pain syndromes.

Radiation Sickness: An Analysis of Over 1000 Controlled Drug Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stoll, B A

1962-08-25

in 265 cases of breast irradiation, the new tranquilizers are significantly superior to all others. Anorexia after irradiation may originate in the appetite center or have a different cause such as delayed gastric emptying. Separate origins for vomiting and for anorexia may account for the superior effect noted with the newer tranquilizers on the symptoms of nausea and vomiting and the greatly inferior effect on anorexia. The tranquilizers may act by sedating the vomiting center. Evidence was found for a specific deficiency of pyridoxine in some cases of radiation sickness. Whether this is a direct effect on enzymes, an effect on the bowel, or a result of metabolic changes associated with vomiting is uncertain. Nevertheless pyridoxine may be of value even if other anti-emetic drugs fail to control the symptoms of radiation sickness.« less

Extending the Bacillus cereus group genomics to putative food-borne pathogens of different toxicity.

PubMed

Lapidus, Alla; Goltsman, Eugene; Auger, Sandrine; Galleron, Nathalie; Ségurens, Béatrice; Dossat, Carole; Land, Miriam L; Broussolle, Veronique; Brillard, Julien; Guinebretiere, Marie-Helene; Sanchis, Vincent; Nguen-The, Christophe; Lereclus, Didier; Richardson, Paul; Wincker, Patrick; Weissenbach, Jean; Ehrlich, S Dusko; Sorokin, Alexei

2008-01-30

The Bacillus cereus group represents sporulating soil bacteria containing pathogenic strains which may cause diarrheic or emetic food poisoning outbreaks. Multiple locus sequence typing revealed a presence in natural samples of these bacteria of about 30 clonal complexes. Application of genomic methods to this group was however biased due to the major interest for representatives closely related to Bacillus anthracis. Albeit the most important food-borne pathogens were not yet defined, existing data indicate that they are scattered all over the phylogenetic tree. The preliminary analysis of the sequences of three genomes discussed in this paper narrows down the gaps in our knowledge of the B. cereus group. The strain NVH391-98 is a rare but particularly severe food-borne pathogen. Sequencing revealed that the strain should be a representative of a novel bacterial species, for which the name Bacillus cytotoxis or Bacillus cytotoxicus is proposed. This strain has a reduced genome size compared to other B. cereus group strains. Genome analysis revealed absence of sigma B factor and the presence of genes encoding diarrheic Nhe toxin, not detected earlier. The strain B. cereus F837/76 represents a clonal complex close to that of B. anthracis. Including F837/76, three such B. cereus strains had been sequenced. Alignment of genomes suggests that B. anthracis is their common ancestor. Since such strains often emerge from clinical cases, they merit a special attention. The third strain, KBAB4, is a typical facultative psychrophile generally found in soil. Phylogenic studies show that in nature it is the most active group in terms of gene exchange. Genomic sequence revealed high presence of extra-chromosomal genetic material (about 530kb) that may account for this phenomenon. Genes coding Nhe-like toxin were found on a big plasmid in this strain. This may indicate a potential mechanism of toxicity spread from the psychrophile strain community. The results of this genomic

Attitude and practice of medical students studying in Hungary and India toward health during overseas and domestic travel.

PubMed

Sweni, Shah; Muthusundari, Arunachalam; Meenakshisundaram, Ramachandran; Uma, Alagappan; Thirumalaikolundusubramanian, Ponniah

2010-01-01

It is presumed that medical students are travelers who can take care of their health, and thus the present study was conducted to elicit the attitude and practice [AP] of medical students from two different countries toward travel health issues. To elicit the attitude and practice of medical students from two different countries toward travel health issues and identify the reasons for any variations. An anonymous pre-tested structured questionnaire consisting of socio-demographic details, travel aspects, travel health issues, and precautions [medicines carried, vaccination history, and pre-travel consultation] adopted was distributed to 250 foreign medical students studying at the University of Debrecen, Hungary [Group I] and another 250 native medical students in India [Group II]. Data were analyzed by simple descriptive statistics and Student t-test. A total of 428 students responded among total eligible population of 500; 228 [90.2%] in group I and 200 [80%] in group II. In 2008, 188 [82%] of the former and 33 [16.5%] of the latter groups traveled to international destinations. Among groups I and II, health problems were experienced by 73 [32%] and 65 [32.5%] students, respectively. During hospitalization, students of group I were admitted for one of the following illnesses such as severe asthma, dehydration, malaria, and tibial fracture, while two other students were admitted to the hospital with deep vein thrombosis [DVT]. During travel, the category of medicines carried by students belonging to group I/II were anti-diarrhoeal [75/19], anti-emetics [53/39], anti-giddiness [49/7], anti-histamines [55/12], anti-pyretics plus analgesics [197/70], anti-spasmodics [55/11], antibiotics [33/10], vitamin pills [84/0], and laxatives [47/6]; supportive items such as adhesive plaster [64/3], and thermometer [37/1]; personal protective materials viz., mineral water [165/88], hygienic food [100/132], insect repellents [86/14], special clothes such as full sleeves and cap

Historical development of modern anesthesia.

PubMed

Robinson, Daniel H; Toledo, Alexander H

2012-06-01

in 1937. He was the first to describe the routinely placing of the tip of his newly re-designed laryngoscope in the epiglottic vallecula which is attached to the base of the tongue, thus when lifted exposed the entire larynx. Macintosh was genuinely astonished at what a great view he could achieve with his new blade and technique. The use of barbiturates as an intravenous anesthetic began in 1932. Sodium thiopental gained popularity after its use was described in detail by a Dr. John Lundy (1894-1973) of the Mayo Clinic. Other I.V. medications were tried over the past seventy years, but the newest induction drug which provided for a substantially shorter recovery period and seemed to actually suppress laryngeal reflexes has brought with it many benefits. Propofol, introduced clinically in 1977, demonstrated many positive effects even as an anti-emetic compound. Before October of 1846, surgery and pain were synonymous but not thereafter. As we entered the information age where the infrastructure of evidence based medicine and newer fields of genetics, transplantation, imaging radiology and even stem cells became quickly integrated into mainstream medicine, we can predict an excellent future on the progress to be made in anesthesia.

Motor effects of the non-psychotropic phytocannabinoid cannabidiol that are mediated by 5-HT1A receptors.

PubMed

Espejo-Porras, Francisco; Fernández-Ruiz, Javier; Pertwee, Roger G; Mechoulam, Raphael; García, Concepción

2013-12-01

were reversed by the 5-HT1A receptor antagonist WAY-100,635 (0.5 mg/kg; i.p.); (v) the effects of CBD (20 mg/kg) on vertical activity were not reversed by the CB1 receptor antagonist rimonabant (0.1 mg/kg; i.p.); (vi) the effect of 8-OH-DPAT on vertical activity was associated with an increase in serotonin content in the basal ganglia, a neurochemical change not produced by CBD (20 mg/kg); and (vii) CBD at a dose of 20 mg/kg was able to enhance motor effects of a sub-effective dose of 8-OH-DPAT (0.1 mg/kg), producing the expected changes in serotonergic transmission in the basal ganglia. Collectively, these results suggest that CBD may influence motor activity, in particular vertical activity, and that this effect seems to be dependent on its ability to target the 5-HT1A receptor, a mechanism of action that has been proposed to account for its anti-emetic, anxiolytic and antidepressant effects. Copyright © 2013 Elsevier Ltd. All rights reserved.

Contributions to the phytotherapies of digestive disorders: Traditional knowledge and cultural drivers of Manoor Valley, Northern Pakistan.

PubMed

Rahman, Inayat Ur; Ijaz, Farhana; Afzal, Aftab; Iqbal, Zafar; Ali, Niaz; Khan, Shujaul Mulk

2016-11-04

medicinal plants with most use values were Ficus carica having (UV i =0.90) and Trifolium repens (UV i =0.84). Based on the RFC values, the most cited medicinal plant species by the traditional drivers were Ficus carica (0.43) and Berberis lycium (0.41), while most respondents percentage was noticed for same plant species calculated through consensus index (CI%=42.9% and 41.3%) respectively. The medicinal plant species with highest fidelity level was of Grewia optiva, Juglans regia and Sorbaria tomentosa each cited 100% for anthelmintic, easy digestion and Diarrhea respectively. Due to representation by only single medicinal plant taxa (Nt=1), the digestive diseases viz. cholera, colon cancer, emetic, internal injuries, kill microorganisms, Soothing, tumor and urine suppression had maximum F IC value. The analytical result reveals that 57% of medicinal plant species were reported for the first time regarding their uses. new medicinal uses of Anaphalis contorta, Caltha palustris, Pinus wallichiana, Plantago himalaica were recorded for the first time from Pakistan and Aralia cachemirica, Bupleurum longicaule, Pleurospermum stellatum, Potentilla argentea and Juglans regia across the globe for currently reported medicinal uses. Besides this, all the mentioned plant species were reported for the first time for digestive disorders from Manoor Valley as no single study up-till now has been conducted ethno medicinally. The present study revealed the importance to document and launch list of all the possible plants that are used in traditional medicinal practices against digestive disorders in the unexplored study area and to show the important medicinal plants for future biological, phytochemical and pharmacological experimentation regarding digestive problems. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.