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Sample records for leukotrienes induce emesis

  1. Radiotherapy-induced emesis. An overview

    International Nuclear Information System (INIS)

    Feyer, P.; Buchali, A.; Hinkelbein, M.; Budach, V.; Zimmermann, J.S.; Titlbach, O.J.

    1998-01-01

    Background: A significant number of patients receiving radiotherapy experience the distressing side effects of emesis and nausea. These symptoms are some of the most distressing problems for the patients influencing their quality of life. Methods: International study results concerning radiotherapy-induced emesis are demonstrated. A German multicenter questionnaire examining the strategies to prevent or to treat radiotherapy-induced nausea and emesis is presented. An international analysis concerning incidence of emesis and nausea in fractionated radiotherapy patients is discussed. Finally the consensus of the consensus conference on antiemetic therapy from the Perugia International Cancer Conference V is introduced. Results: Untreated emesis can lead to complications like electrolyte disorders, dehydration, metabolic disturbances and nutrition problems with weight loss. Prophylactic antiemetics are often given to patients receiving single high-dose radiotherapy to the abdomen. A survey has revealed that antiemetic prophylaxis is not routinely offered to the patients receiving fractionated radiotherapy. However, there is a need for an effective treatment of emesis for use in this group of patients, too. In 20% of patients nausea and emesis can cause a treatment interruption because of an inadequate control of symptoms. Like in chemotherapy strategies there exist high, moderate, and low emetogenic treatment regimens in radiotherapy as well. The most emetogenic potential has the total body irradiation followed by radiotherapy to the abdomen. Radiotherapy induced emesis can be treated effectively with conventional antiemetics up to 50%. Conclusions: Studies with total body irradiation, fractionated treatment and high-dose single exposures have cleary demonstrated the value of 5-HT3-receptor antagonist antiemetics. There is a response between 60 and 97%. There is no difference in the efficacy of the different 5-HT3-antagonists. High-risk patients should be prophylactic

  2. Radiotherapy-induced emesis. An overview

    Energy Technology Data Exchange (ETDEWEB)

    Feyer, P.; Buchali, A.; Hinkelbein, M.; Budach, V. [Department Radiotherapy, Humboldt-University Berlin (Germany); Zimmermann, J.S. [Department Radiotherapy, Christian Albrechts-University Kiel (Germany); Titlbach, O.J. [Department of Medicine I, Hospital Friedrichshain, Berlin (Germany)

    1998-11-01

    Background: A significant number of patients receiving radiotherapy experience the distressing side effects of emesis and nausea. These symptoms are some of the most distressing problems for the patients influencing their quality of life. Methods: International study results concerning radiotherapy-induced emesis are demonstrated. A German multicenter questionnaire examining the strategies to prevent or to treat radiotherapy-induced nausea and emesis is presented. An international analysis concerning incidence of emesis and nausea in fractionated radiotherapy patients is discussed. Finally the consensus of the consensus conference on antiemetic therapy from the Perugia International Cancer Conference V is introduced. Results: Untreated emesis can lead to complications like electrolyte disorders, dehydration, metabolic disturbances and nutrition problems with weight loss. Prophylactic antiemetics are often given to patients receiving single high-dose radiotherapy to the abdomen. A survey has revealed that antiemetic prophylaxis is not routinely offered to the patients receiving fractionated radiotherapy. However, there is a need for an effective treatment of emesis for use in this group of patients, too. In 20% of patients nausea and emesis can cause a treatment interruption because of an inadequate control of symptoms. Like in chemotherapy strategies there exist high, moderate, and low emetogenic treatment regimens in radiotherapy as well. The most emetogenic potential has the total body irradiation followed by radiotherapy to the abdomen. Radiotherapy induced emesis can be treated effectively with conventional antiemetics up to 50%. Conclusions: Studies with total body irradiation, fractionated treatment and high-dose single exposures have cleary demonstrated the value of 5-HT3-receptor antagonist antiemetics. There is a response between 60 and 97%. There is no difference in the efficacy of the different 5-HT3-antagonists. High-risk patients should be prophylactic

  3. Reducing radiation induced emesis in abdominal radiotherapy

    International Nuclear Information System (INIS)

    Griffin, K.

    1994-01-01

    In patients with seminoma testes, a comparison was made between radiation induced emesis suffered by patients receiving 'dogleg' radiotherapy with those suffered by patients who received para-aortic radiotherapy. The same comparisons were made between the effects suffered by those patients who received the anti-emetic, Ondansetron, and those suffered by patients who received conventional anti-emetics. (UK)

  4. X-irradiation-induced emesis in Suncus murinus

    International Nuclear Information System (INIS)

    Torii, Yoshifumi; Saito, Hiroshi; Matsuki, Norio; Shikita, Mikio.

    1993-01-01

    X-irradiation-induced emesis was investigated in Suncus murinus, a house musk shrew. Whole body X-irradiation caused emesis, and the calculated ED 50 value that induced emesis in 50% of animals was 429 cGy. At the irradiation dose of 800 cGy all the animals vomited 10.0±2.4 times with a latency of 20.0±2.9 min. The emetogenic effect of X-irradiation was dependent on the part of the body exposed. Abdominal X-irradiation at 1000 cGy caused emesis in all animals studied, whereas the same dose to the head had no emetogenic effect. We investigated several prophylactic methods against X-irradiation-induced emesis. Surgical vagotomy completely inhibited the emesis induced by 800 cGy X-irradiation. Emesis was also prevented by the subcutaneous administration of tropisetron (ICS 205-930, a selective serotonergic 5-HT 3 receptor antagonist) with an ID 50 value of 29 μg/kg. These results suggest that (1) suncus is a useful experimental animal for the study of radiation-induced emesis and the development of prophylactic drugs, (2) serotonin plays an important role in X-irradiation-induced emesis, and (3) X-irradiation-induced emesis is very similar to that caused by cancer chemotherapeutic agents. (author)

  5. Radiation-induced emesis in monkeys

    International Nuclear Information System (INIS)

    Mattsson, J.L.; Yochmowitz, M.G.

    1980-01-01

    To determine the emesis ED 50 for 60 Co radiation, 15 male rhesus monkeys were exposed to whole-body radiation doses ranging from 350 to 550 rad midline tissue dose. An up-and-down sequence of exposures was used. Step size between doses was 50 rad, and dose rate was 20 rad/min. There had been no access to food for 1 to 2 h. The ED 50 +- SE was found to be 446 +- 27 rad. To determine the effect of motion on emesis ED 50 , six more monkeys were exposed to 60 Co radiation as above, except that the chair in which they were seated was oscillated forward and backward 5 to 15 0 (pitch axis) at a variable rate not exceeding 0.3 Hz. Radioemesis ED 50 +- SE with motion was 258 +- 19 rad, a value significantly lower (P < 0.01) than for stationary monkeys

  6. Characterization of radiation-induced emesis in the ferret

    International Nuclear Information System (INIS)

    King, G.L.

    1988-01-01

    Forty-eight ferrets (Mustela putorius furo) were individually head-shielded and radiated with bilateral 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 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 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

  7. Behavioral patterns associated with chemotherapy-induced emesis: A potential signature for nausea in musk shrews

    Directory of Open Access Journals (Sweden)

    Charles Christopher Horn

    2011-07-01

    Full Text Available Nausea and vomiting are common symptoms in patients with many diseases, including cancer and its treatments. Although the neurological basis of vomiting is reasonably well known, an understanding of the physiology of nausea is lacking. The primary barrier to mechanistic research on the nausea system is the lack of an animal model. Indeed investigating the effects of anti-nausea drugs in preclinical models is difficult because the primary readout is often emesis. It is known that animals show a behavioral profile of sickness, associated with reduced feeding and movement, and possibly these general measures are signs of nausea. Studies attempting to relate the occurrence of additional behaviors to emesis have produced mixed results. Here we applied a statistical method, t-pattern (temporal pattern analysis, to determine patterns of behavior associated with emesis. Musk shrews were injected with the chemotherapy agent cisplatin (a gold standard in emesis research to induce acute (< 24 h and delayed (> 24 h emesis. Emesis and other behaviors were coded and tracked from video files. T-pattern analysis revealed hundreds of non-random patterns of behavior associated with emesis, including sniffing, changes in body contraction, and locomotion. There was little evidence that locomotion was inhibited by the occurrence of emesis. Eating and drinking, and other larger body movements including rearing, grooming, and body rotation, were significantly less common in emesis-related behavioral patterns in real versus randomized data. These results lend preliminary evidence for the expression of emesis-related behavioral patterns, including reduced ingestive behavior, grooming and exploratory behaviors. In summary, this statistical approach to behavioral analysis in a pre-clinical emesis research model could be used to assess the more global effects and limitations of drugs used to control nausea and its potential correlates, including reduced feeding and

  8. Radiation-induced emesis in the dog: effects of lesions and drugs

    International Nuclear Information System (INIS)

    Carpenter, D.O.; Briggs, D.B.; Knox, A.P.; Strominger, N.L.

    1986-01-01

    Dogs exposed to 8 Gy 60 Co gamma mid-abdominal irradiation exhibited emesis with an average latency of 102 min and an average of 7.4 episodes over 96 min. There were no significant changes in dogs subjected to a chronic bilateral subdiaphragmatic vagotomy, but emesis was prevented by ablation of the area postrema. Indomethacin pretreatment also prevented radiation-induced emesis in two of seven dogs and in the remainder reduced the average number of episodes. Domperidone pretreatment prevented radiation-induced emesis in all of four dogs tested. In electrophysiological studies recording from the area postrema the chemosensitive neurons were found to be normally silent in anesthetized preparations but excitable by a variety of emetic agents. After irradiation of the abdomen spontaneously active neurons were found with a discharge pattern that mirrored the behavioral pattern of postirradiation emesis. These studies are consistent with radiation-induced emesis being humorally mediated in the dog and implicate dopamine and/or prostaglandins as possible mediators

  9. On the mechanism of radiation-induced emesis: The role of serotonin

    International Nuclear Information System (INIS)

    Scarantino, C.W.; Ornitz, R.D.; Hoffman, L.G.

    1994-01-01

    The aim of this study was to determine the mechanism of action of radiation-induced emesis by determining the incidence of radiation-induced emesis following hemibody irradiation; the effects of specific antiemetics especially ondansetron, a 5-hydroxytryptamine receptor antagonist, and to determine the relationship between radiation-induced emesis and serotonin (5-hydroxytryptamine) through its active metabolite, 5-hydroxyindoleacetic acid (5-HIAA). Forty-one patients received 53 hemibody treatments of 5-8 Gy following intravenous hydration. The patients were divided into three groups according to prehemibody irradiation treatment: Group A: no pretreatment antiemetics, 30 patients; Group B: nonondansetron antiemetics (metoclopramide, dexamethasone, prochlorperazine), ten patients; and Group C: ondansetron, 13 patient. The incidence of radiation-induced emesis was determined prehemibody irradiation or baseline and at 1 h posthemibody irradiation in 38 patients and the results expressed as the percent change in 5-HIAA (ng/ug creatinine). The incidence of radiation-induced emesis was 82% (14/17) following upper/mid hemibody irradiation and 15% (2/11) following lower hemibody irradiation in Group A; 50% (3/6) and 25% (1/4) following upper/mid and lower hemibody irradiation respectively, in Group B/; and 0% (p/13) after upper/mid hemibody irradiation in Group C. The incidence of emesis was significantly different (p<0.001) between the patients of Group A and C who received upper/mid hemibody irradiation. The percent change in 5-HIAA excretion following upper/mid hemibody irradiation were greatest in Group A and smallest in Group C (p<0.002). The degree of change following lower hemibody irradiation (15% incidence of emesis) in Group A was lower than upper/mid hemibody irradiation of the same group. 17 refs., 3 figs., 2 tabs

  10. Role of the area postrema in radiation-induced taste aversion learning and emesis in cats

    International Nuclear Information System (INIS)

    Rabin, B.M.; Hunt, W.A.; Chedester, A.L.; Lee, J.

    1986-01-01

    The role of the area postrema in radiation-induced emesis and taste aversion learning and the relationship between these behaviors were studied in cats. The potential involvement of neural factors which might be independent of the area postrema was minimized by using low levels of ionizing radiation (100 rads at a dose rate of 40 rads/min) to elicit a taste aversion, and by using body-only exposures (4500 and 6000 rads at 450 rads/min) to produce emesis. Lesions of the area postrema disrupted both taste aversion learning and emesis following irradiation. These results, which indicate that the area postrema is involved in the mediation of both radiation-induced emesis and taste aversion learning in cats under these experimental conditions, are interpreted as being consistent with the hypotheses that similar mechanisms mediate both responses to exposure to ionizing radiation, and that the taste aversion learning paradigm can therefore serve as a model system for studying radiation-induced emesis

  11. Efficacy of ondansetron in the management of radiotherapy induced emesis: a review

    International Nuclear Information System (INIS)

    Levy, E.; Paillarse, J.M.; Votan, B.

    1994-01-01

    Radiotherapy-induced emesis depends on the site of irradiation, the field size and the dose per fraction and is generally less intense than chemotherapy-induced emesis. Established anti-emetic drugs offer only limited symptom control (50%). Ondansetron, a 5HT 3 receptors antagonist, had proven a complete or a major control efficacy (0-2 emetic episodes) of 68 to 95% in three pilot studies (fractionated, single-dose and total body irradiations). In controlled studies, ondansetron efficacy was significantly higher than placebo, metoclopramide and prochlorperazine. The treatment was well tolerated in the different studies. (authors). 23 refs., 2 figs., 1 tab

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

    Science.gov (United States)

    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.

  13. Radiation-induced emesis: a prospective observational multicenter Italian trial

    International Nuclear Information System (INIS)

    1999-01-01

    Purpose: A prospective observational multicenter trial was carried out to assess the incidence, pattern, and prognostic factors of radiation-induced emesis (RIE), and evaluate the use of antiemetic drugs in radiation oncology clinical practice. Methods and Materials: Fifty-one Italian radiation oncology centers took part in this trial. The accrual lasted 2 consecutive weeks, only patients starting radiotherapy in this period were enrolled. Exclusion criteria were age under 18 years, and concomitant chemotherapy. Evaluation was based on diary cards filled in daily by patients during radiotherapy and 1 week after stopping it. Diary cards recorded the intensity of nausea and any episode of vomiting and retching. Prophylactic and symptomatic antiemetic drug prescriptions were also registered. Results: Nine hundred thirty-four patients entered the trial, and 914 were evaluable. Irradiated sites were: breast in 211 patients, pelvis in 210 patients, head and neck in 136 patients, thorax in 129 patients, brain in 52 patients, upper abdomen in 42 patients, skin and/or extremities in 37 patients, and other sites in 97 patients. Vomiting and nausea occurred in 17.1% and 37.3% of patients, respectively, and 38.7% patients had both vomiting and nausea. At multifactorial analysis, the only patient-related risk factor that was statistically significant was represented by previous experience with cancer chemotherapy. Moreover, two radiotherapy (RT)-related factors were significant risk factors for RIE, the irradiated site and field size. In fact, a statistically significant higher percentage of RIE was registered in upper abdomen RT and RT fields > 400 cm 2 . Although nonstatistically significant, patients receiving RT to the thorax and head and neck presented a higher incidence of RIE. Only a minority (14%) of patients receiving RT were given an antiemetic drug, and the prescriptions were more often symptomatic than prophylactic (9% vs. 5%, respectively). Different compounds and

  14. Comparison of the use of sodium carbonate (washing soda crystals) and apomorphine for inducing emesis in dogs.

    Science.gov (United States)

    Yam, E; Hosgood, G; Smart, L

    2016-12-01

    To describe the use of sodium carbonate and apomorphine in a historical cohort of dogs, compare the occurrence of emesis and report any adverse effects recorded. This historical, observational study included information from medical records of dogs that received an emetic agent. The occurrence of emesis with apomorphine or sodium carbonate was calculated and the association between emesis and agent was explored, with the odds ratio and 95% confidence interval (CI) reported. A non-inferiority analysis of the occurrence of emesis for sodium carbonate was performed against an equivalence range of ±7% of the estimated occurrence of emesis with apomorphine. Owners were emailed a short survey about their dog's health after their visit to the hospital for induced emesis. Records for 787 dogs seen from January 2007 to December 2013 were included. For apomorphine, 382/392 dogs showed emesis (97%, 95% CI 95-100%). For sodium carbonate, 320/395 dogs showed emesis (81%, 95% CI 77-85%), which fell below the equivalence range for apomorphine (97 ± 7%, 90-100%) and was considered inferior. The odds ratio of emesis with apomorphine to sodium carbonate was 9.0 (95% CI 4.6-17.6). Of 18 responses to the survey, 5 reported abnormalities after emesis (3 with sodium carbonate, 2 with apomorphine). The occurrence of emesis with sodium carbonate was high but inferior to apomorphine. However, the advantages of sodium carbonate, including less expense and ease of accession compared with apomorphine, make it a viable choice in emergency medicine. © 2016 Australian Veterinary Association.

  15. Leukotriene E4 induces airflow obstruction and mast cell activation through the cysteinyl leukotriene type 1 receptor.

    Science.gov (United States)

    Lazarinis, Nikolaos; Bood, Johan; Gomez, Cristina; Kolmert, Johan; Lantz, Ann-Sofie; Gyllfors, Pär; Davis, Andy; Wheelock, Craig E; Dahlén, Sven-Erik; Dahlén, Barbro

    2018-03-05

    Leukotriene (LT) E 4 is the final active metabolite among the cysteinyl leukotrienes (CysLTs). Animal studies have identified a distinct LTE 4 receptor, suggesting that current cysteinyl leukotriene type 1 (CysLT 1 ) receptor antagonists can provide incomplete inhibition of CysLT responses. We tested this hypothesis by assessing the influence of the CysLT 1 antagonist montelukast on responses induced by means of inhalation of LTE 4 in asthmatic patients. Fourteen patients with mild intermittent asthma and 2 patients with aspirin-exacerbated respiratory disease received 20 mg of montelukast twice daily and placebo for 5 to 7 days in a randomized, double-blind, crossover study (NCT01841164). The PD 20 value was determined at the end of each treatment period based on an increasing dose challenge. Measurements included lipid mediators in urine and sputum cells 4 hours after LTE 4 challenge. Montelukast completely blocked LTE 4 -induced bronchoconstriction. Despite tolerating an at least 10 times higher dose of LTE 4 after montelukast, there was no difference in the percentage of eosinophils in sputum. Urinary excretion of all major lipid mediators increased after LTE 4 inhalation. Montelukast blocked release of the mast cell product prostaglandin (PG) D 2 , as well as release of PGF 2α and thromboxane (Tx) A 2 , but not increased excretion of PGE 2 and its metabolites or isoprostanes. LTE 4 induces airflow obstruction and mast cell activation through the CysLT 1 receptor. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Effectiveness of antiemetics in control of antineoplastic chemotherapy-induced emesis at home

    OpenAIRE

    Castro,Marielly Cunha; Araújo,Suely Amorim de; Mendes,Thaís Rezende; Vilarinho,Glauciane Silva; Mendonça,Maria Angélica Oliveira

    2014-01-01

    Objective Evaluating if antiemetics are effective in the prevention or treatment at home, of chemotherapy-induced emesis. Methods In total, were included 42 women with breast cancer in moderately emetogenic chemotherapy, using dexamethasone/ondansetron before each cycle. The frequency of nausea and vomiting was obtained by applying the instrument in the pre-chemotherapy period, and 24h, 48h, 72h and 96h after chemotherapy. The use of antiemetics was considered in accordance with adherence...

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

    International Nuclear Information System (INIS)

    Warneck, Julie B.; Cheng, Frankie H.M.; Barnes, Matthew J.; Mills, John S.; Montana, John G.; Naylor, Robert J.; Ngan, Man-P.; Wai, Man-K.; Daiss, Juergen O.; Tacke, Reinhold; Rudd, John A.

    2008-01-01

    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 3 receptor antagonist, a glucocorticoid, and an NK 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 0.05). 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

  18. Control of radiation-induced emesis with promethazine, cimetidine, thiethylperazine, or naloxone

    International Nuclear Information System (INIS)

    Cooper, J.R.; Mattsson, J.L.

    1979-01-01

    Promethazine (2 mg/kg), cimetidine (4 mg;kg), thiethylperazine (0.86 mg/kg), and naloxone (0.08 mg/kg) were each evaluated for their ability to increase the threshold of radiation-induced emesis in the dog. Each dog was fed a can of dog food (ca 0.4 kg) and then injected IM with the appropriate drug 1 hour before being irradiated by a 60 Co teletherapy unit. Dogs were then observed continuously for 10 hours while the number, time of onset, and duration of each emetic episode were monitored. The dose of radiation causing emesis in 50% control dogs was 170 rad. The ED50 was increased to 402 rad by promethazine, to 331 rad by cimetidiene, and to 320 rad by thiethylperazine. The ED50 for naloxone was 262.5 rad, which was not a statistically significant increase in threshold

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

    Directory of Open Access Journals (Sweden)

    Ihsan Ullah

    2017-04-01

    Full Text Available 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. 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.

  20. Contribution to the treatment of nausea and emesis induced by chemotherapy in children and adolescents with osteosarcoma

    Directory of Open Access Journals (Sweden)

    Flavio Augusto Vercillo Luisi

    Full Text Available CONTEXT AND OBJECTIVE: Chemotherapy-induced emesis is a limiting factor in treating children with malignancies. Intensive chemotherapy regimens along with emetogenic drug administration have increased the frequency and severity of emesis and nausea. Our study was designed to consider the importance of this problem and the need for improvement in emesis treatment for patients receiving chemotherapy. Our objective was to compare the efficacy and safety of the antiemetic drug granisetron and a regimen of metoclopramide plus dimenhydrinate. DESIGN AND SETTING: Open, prospective and randomized study at Instituto de Oncologia Pediátrica, Department of Pediatrics, Universidade Federal de São Paulo. METHODS: From February to August 1994, 26 patients (mean age: 14 years with osteosarcoma received 80 chemotherapy cycles of iphosphamide (2,500 mg/m² plus epirubicin (75 mg/m² or carboplatin (600 mg/m², or epirubicin (75 mg/m² plus carboplatin (600 mg/m². Eighty chemotherapy treatments were analyzed regarding nausea and vomiting control. Patients were randomized to receive either a single dose of granisetron (50 µg/kg or metoclopramide (2 mg/kg plus dimenhydrinate (5 mg/kg infused over eight hours. Emesis and nausea were monitored for 24 hours by means of the modified Morrow Assessment of Nausea and Emesis. Statistical analysis utilized the chi-squared, Student t and Mann-Whitney tests, plus data exploration techniques. RESULTS: 62.5% of the patients undergoing chemotherapy responded completely to granisetron, whereas 10% responded to metoclopramide plus dimenhydrinate (p < 0.0001. No severe adverse reactions were found in either of the treatments given. CONCLUSION: In children and adolescents with osteosarcoma, granisetron was safe and more efficient than metoclopramide plus dimenhydrinate for controlling chemotherapy-induced emesis and nausea.

  1. Is there a role for leukotrienes as mediators of ethanol-induced gastric mucosal damage?

    International Nuclear Information System (INIS)

    Wallace, J.L.; Beck, P.L.; Morris, G.P.

    1988-01-01

    The role of leukotriene (LT) C 4 as a mediator of ethanol-induced gastric mucosal damage was investigated. Rats were pretreated with a number of compounds, including inhibitors of leukotriene biosynthesis and agents that have previously been shown to reduce ethanol-induced damage prior to oral administration of absolute ethanol. Ethanol administration resulted in a fourfold increase in LTC 4 synthesis. LTC 4 synthesis could be reduced significantly by pretreatment with L651,392 or dexamethosone without altering the susceptibility of the gastric mucosa to ethanol-induced damage. Furthermore, changes in LBT 4 synthesis paralleled the changes in LTC 4 synthesis observed after ethanol administration. The effects of ethanol on gastric eicosanoid synthesis were further examined using an ex vivo gastric chamber preparation that allowed for application of ethanol to only one side of the stomach. These studies confirm that ethanol can stimulate gastric leukotriene synthesis independent of the production of hemorrhagic damage. Inhibition of LTC 4 synthesis does not confer protection to the mucosa, suggesting that LTC 4 does not play an important role in the etiology of ethanol-induced gastric damage

  2. Antiemetic effects of lerisetron in radiation-induced emesis in the dog

    International Nuclear Information System (INIS)

    Gomez-de-Segura, I.A.; De Miguel, E.; Grande, A.G.

    1998-01-01

    The 5-HT 3 receptor antagonists are the most potent antiemetics known at present. Lerisetron is a new 5-HT 3 receptor antagonist chemically unrelated to other antagonists like Ondansetron. An emesis model in the dog induced by irradiation with 60 Co was used, and 8 Gy were administered over the total body surface. An irradiated control group was established and received no medication, and two irradiated groups received treatment with either Ondansetron or Lerisetron. The 'up-down' technique was employed to determine the effective dose (ED 50 ). A logarithmic scale was used to increase or decrease the doses in each case. The initial doses were 300 μg/kg for Ondansetron and 100 μg/kg for Lerisetron. All animals in the control group vomited. The ED 50 of Ondansetron was 178 ± 151 μg/kg body wt and that of Lerisetron was 63 ± 18 μg/kg. Lerisetron is more potent and presented less individual variability than Ondansetron, but its antiemetic effects were equally effective. (orig.)

  3. Radiation-induced emesis in cats prevented by 24-hour prior exposure but not by ablation of the area postrema

    International Nuclear Information System (INIS)

    McCarthy, L.E.; Borison, H.L.; Douple, E.B.

    1985-01-01

    The acute emetic response induced by whole body exposure to cobalt radiation was quantified in cats at doses ranging from 1500 to 9000 rad (100 rad/min). Emesis occurred in a dose-related manner with a maximum incidence of 94% at 4500 rad (11 of 12 cats, mean latency of 98 min). At 6000 rad emesis occurred in 7 of 10 cats (mean latency of 69 min); however, a second exposure to this dose on the following day failed to induce vomiting in all of 5 cats (difference between groups significant at p = .01). After chronic ablation of the area postrema (chemoreceptor trigger zone for vomiting), 4 of 5 cats vomited in response to 4500 rad with a mean latency of 48 min. As was the case with the normal cats, all the postrema-ablated animals failed to vomit in response to a repeated dose of radiation delivered on the next day. The suppression of emesis observed on the second exposure was radiation-specific because 11 of 12 normal cats vomited appropriately in response to xylazine (0.6 mg/kg, im) during the period of refractoriness to radiation

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

    International Nuclear Information System (INIS)

    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 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 that 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

  5. Exercise-induced bronchoconstriction: The effects of montelukast, a leukotriene receptor antagonist

    Directory of Open Access Journals (Sweden)

    James P Kemp

    2009-11-01

    Full Text Available James P KempClinical Professor of Pediatrics, Division of Immunology and Allergy, University of California School of Medicine, San Diego, CA, USAAbstract: Exercise-induced bronchoconstriction (EIB is very common in both patients with asthma and those who are otherwise thought to be normal. The intensity of exercise as well as the type of exercise is important in producing symptoms. This may make some types of exercise such as swimming more suitable and extended running more difficult for patients with this condition. A better understanding of EIB will allow the physician to direct the patient towards a type of exercise and medications that can result in a more active lifestyle without the same concern for resulting symptoms. This is especially important for schoolchildren who are usually enrolled in physical education classes and elite athletes who may desire to participate in competitive sports. Fortunately several medications (short- and long-acting β2-agonists, cromolyn, nedocromil, inhaled corticosteroids, and more recently leukotriene modifiers have been shown to be effective in preventing or attenuating the effects of exercise in many patients. In addition, inhaled β2-agonists have been shown to quickly reverse the airway obstruction that develops in patients and continue to be the reliever medications of choice. Inhaled corticosteroids are increasingly being recommended as regular therapy now that the role of inflammation and airway injury has been identified in EIB. With the discovery that there is a release of mediators such as histamine and leukotrienes from cells in the airway following exercise with resulting airway obstruction in susceptible individuals, interest has turned to attenuating their effects with mediator antagonists especially those that block the effects of leukotrienes. Studies with an oral leukotriene antagonist, montelukast, have shown beneficial effects in adults and children aged as young as 6 years with EIB

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  8. The effect of ondansetron on radiation-induced emesis and diarrhoea

    International Nuclear Information System (INIS)

    Henriksson, R.; Lomberg, H.; Israelsson, G.; Zackrisson, B.; Franzen, L.

    1992-01-01

    Ondansetron is a new 5-HT 3 -antagonist with antiemetic properties. In this consecutive study, 33 patients receiving fractionated upper abdominal irradiation (≥ 100 cm 2 , 1,8-4 Gy daily dose for a mean of 13 days) were treated with ondansetron (8 mg t.d.s. p.o.). Emesis was completely controlled in 26/33 (79%) patients throughout their radiation course, which embraced 628 (94%) treatment days. Ondansetron was well tolerated. Eleven patients developed mild constipation. No patients experienced diarrhoea (a common distressing side-effect of abdominal irradiation). It is suggested that ondansetron can be of value in preventing emesis in patients receiving fractionated radiotherapy. The possible beneficial effect in preventing diarrhoea must be further evaluated. (orig./MG)

  9. Behavioral patterns associated with chemotherapy-induced emesis: A potential signature for nausea in musk shrews

    OpenAIRE

    Charles Christopher Horn; Charles Christopher Horn; Charles Christopher Horn; Charles Christopher Horn; Séverine eHenry; Kelly eMeyers; Magnus S. Magnusson

    2011-01-01

    Nausea and vomiting are common symptoms in patients with many diseases, including cancer and its treatments. Although the neurological basis of vomiting is reasonably well known, an understanding of the physiology of nausea is lacking. The primary barrier to mechanistic research on the nausea system is the lack of an animal model. Indeed investigating the effects of anti-nausea drugs in preclinical models is difficult because the primary readout is often emesis. It is known that animals show ...

  10. Behavioral Patterns Associated with Chemotherapy-Induced Emesis: A Potential Signature for Nausea in Musk Shrews

    OpenAIRE

    Horn, Charles C.; Henry, Séverine; Meyers, Kelly; Magnusson, Magnus S.

    2011-01-01

    Nausea and vomiting are common symptoms in patients with many diseases, including cancer and its treatments. Although the neurological basis of vomiting is reasonably well known, an understanding of the physiology of nausea is lacking. The primary barrier to mechanistic research on the nausea system is the lack of an animal model. Indeed investigating the effects of anti-nausea drugs in pre-clinical models is difficult because the primary readout is often emesis. It is known that animals show...

  11. Leukotriene B₄-leukotriene B₄ receptor axis promotes oxazolone-induced contact dermatitis by directing skin homing of neutrophils and CD8⁺ T cells.

    Science.gov (United States)

    Lv, Jiaoyan; Zou, Linlin; Zhao, Lina; Yang, Wei; Xiong, Yingluo; Li, Bingji; He, Rui

    2015-09-01

    Leukotriene B4 (LTB4 ) is a lipid mediator that is rapidly generated in inflammatory sites, and its functional receptor, BLT1, is mostly expressed on immune cells. Contact dermatitis is a common inflammatory skin disease characterized by skin oedema and abundant inflammatory infiltrates, primarily including neutrophils and CD8(+) T cells. The role of the LTB4 -BLT1 axis in contact dermatitis remains largely unknown. In this study, we found up-regulated gene expression of 5-lipoxygenase and leukotriene A4 hydrolase, two critical enzymes for LTB4 synthesis, BLT1 and elevated LTB4 levels in skin lesions of oxazolone (OXA)-induced contact dermatitis. BLT1 deficiency or blockade of LTB4 and BLT1 by the antagonists, bestatin and U-75302, respectively, in the elicitation phase caused significant decreases in ear swelling and skin-infiltrating neutrophils and CD8(+) T cells, which was accompanied by significantly reduced skin expression of CXCL1, CXCL2, interferon-γ and interleukin-1β. Furthermore, neutrophil depletion during the elicitation phase of OXA-induced contact dermatitis also caused significant decreases in ear swelling and CD8(+) T-cell infiltration accompanied by significantly decreased LTB4 synthesis and gene expression of CXCL2, interferon-γ and interleukin-1β. Importantly, subcutaneous injection of exogenous LTB4 restored the skin infiltration of CD8(+) T cells in neutrophil-depleted mice following OXA challenge. Collectively, our results demonstrate that the LTB4 -BLT1 axis contributes to OXA-induced contact dermatitis by mediating skin recruitment of neutrophils, which are a major source of LTB4 that sequentially direct CD8(+) T-cell homing to OXA-challenged skin. Hence, LTB4 and BLT1 could be potential therapeutic targets for the treatment of contact dermatitis. © 2015 John Wiley & Sons Ltd.

  12. Leukotriene B4—leukotriene B4 receptor axis promotes oxazolone-induced contact dermatitis by directing skin homing of neutrophils and CD8+ T cells

    Science.gov (United States)

    Lv, Jiaoyan; Zou, Linlin; Zhao, Lina; Yang, Wei; Xiong, Yingluo; Li, Bingji; He, Rui

    2015-01-01

    Leukotriene B4 (LTB4) is a lipid mediator that is rapidly generated in inflammatory sites, and its functional receptor, BLT1, is mostly expressed on immune cells. Contact dermatitis is a common inflammatory skin disease characterized by skin oedema and abundant inflammatory infiltrates, primarily including neutrophils and CD8+ T cells. The role of the LTB4–BLT1 axis in contact dermatitis remains largely unknown. In this study, we found up-regulated gene expression of 5-lipoxygenase and leukotriene A4 hydrolase, two critical enzymes for LTB4 synthesis, BLT1 and elevated LTB4 levels in skin lesions of oxazolone (OXA)-induced contact dermatitis. BLT1 deficiency or blockade of LTB4 and BLT1 by the antagonists, bestatin and U-75302, respectively, in the elicitation phase caused significant decreases in ear swelling and skin-infiltrating neutrophils and CD8+ T cells, which was accompanied by significantly reduced skin expression of CXCL1, CXCL2, interferon-γ and interleukin-1β. Furthermore, neutrophil depletion during the elicitation phase of OXA-induced contact dermatitis also caused significant decreases in ear swelling and CD8+ T-cell infiltration accompanied by significantly decreased LTB4 synthesis and gene expression of CXCL2, interferon-γ and interleukin-1β. Importantly, subcutaneous injection of exogenous LTB4 restored the skin infiltration of CD8+ T cells in neutrophil-depleted mice following OXA challenge. Collectively, our results demonstrate that the LTB4–BLT1 axis contributes to OXA-induced contact dermatitis by mediating skin recruitment of neutrophils, which are a major source of LTB4 that sequentially direct CD8+ T-cell homing to OXA-challenged skin. Hence, LTB4 and BLT1 could be potential therapeutic targets for the treatment of contact dermatitis. PMID:25959240

  13. Role of leukotrienes in NSAID induced gastric ulceration and inflammation in wistar rats

    Directory of Open Access Journals (Sweden)

    Maulik N Gandhi

    2012-06-01

    Full Text Available Objective: To evaluate the effects of Montelukast and Curcumin against indomethacin induced gastric damage in rats in order to assess the role of leukotriene (LTs if any, in non steroidal antiinflammatory drug (NSAID induced gastroinflammation. Methods: The effects of Montelukast (10 mg/kg and Curcumin (100 mg/kg were observed on gastric lesion induced by Indomethacin. The blood samples were analyzed for neutrophil adhesion and lipid peroxide levels in gastric tissue measured spectrophotometrically. The skin vascular permeability study was performed by using compound 48/80 induced vascular permeability model. Results: Montelukast and Curcumin significantly reduced Indomethacin induced gastric lesion score. Pretreatment with Montelukast and Curcumin significantly counteracted Indomethacin induced gastropathy by a combination of its effect on inhibition of neutrophil adherence, through decrease in related production of free radicals that disrupts integrity of stomach mucosa and decrease in vascular permeability as compared to Indomethacin group. The results of the present study further indicates the role of 5-LOX metabolites in NSAIDs induced gastro inflammation and suggests that Montelukast and Curcumin counteracted the Indomethacin induced gastropathy by a combination of its effect on inhibition of neutrophil adherence and through decrease in related production of free radicals that disrupts integrity of stomach mucosa. Conclusions: Experimental data clearly demonstrated the role of LTs was indomethacin induced gastric ulcers. However, inhibition of ulcerogenic events by Montelukast and Curcumin is suggestive of an important balance between COX and 5-LOX products.

  14. The cysteinyl leukotriene 2 receptor contributes to all-trans retinoic acid-induced differentiation of colon cancer cells

    International Nuclear Information System (INIS)

    Bengtsson, Astrid M; Jönsson, Gunilla; Magnusson, Cecilia; Salim, Tavga; Axelsson, Cecilia; Sjölander, Anita

    2013-01-01

    Cysteinyl leukotrienes (CysLTs) are potent pro-inflammatory mediators that are increased in samples from patients with inflammatory bowel diseases (IBDs). Individuals with IBDs have enhanced susceptibility to colon carcinogenesis. In colorectal cancer, the balance between the pro-mitogenic cysteinyl leukotriene 1 receptor (CysLT 1 R) and the differentiation-promoting cysteinyl leukotriene 2 receptor (CysLT 2 R) is lost. Further, our previous data indicate that patients with high CysLT 1 R and low CysLT 2 R expression have a poor prognosis. In this study, we examined whether the balance between CysLT 1 R and CysLT 2 R could be restored by treatment with the cancer chemopreventive agent all-trans retinoic acid (ATRA). To determine the effect of ATRA on CysLT 2 R promoter activation, mRNA level, and protein level, we performed luciferase gene reporter assays, real-time polymerase chain reactions, and Western blots in colon cancer cell lines under various conditions. ATRA treatment induces CysLT 2 R mRNA and protein expression without affecting CysLT 1 R levels. Experiments using siRNA and mutant cell lines indicate that the up-regulation is retinoic acid receptor (RAR) dependent. Interestingly, ATRA also up-regulates mRNA expression of leukotriene C 4 synthase, the enzyme responsible for the production of the ligand for CysLT 2 R. Importantly, ATRA-induced differentiation of colorectal cancer cells as shown by increased expression of MUC-2 and production of alkaline phosphatase, both of which could be reduced by a CysLT 2 R-specific inhibitor. This study identifies a novel mechanism of action for ATRA in colorectal cancer cell differentiation and demonstrates that retinoids can have anti-tumorigenic effects through their action on the cysteinyl leukotriene pathway

  15. Control of polyclonal immunoglobulin production from human lymphocytes by leukotrienes; leukotriene B4 induces an OKT8(+), radiosensitive suppressor cell from resting, human OKT8(-) T cells

    International Nuclear Information System (INIS)

    Atluru, D.; Goodwin, J.S.

    1984-01-01

    We report that leukotriene B4 (LTB4), a 5-lipoxygenase metabolite of arachidonic acid, is a potent suppressor of polyclonal Ig production in pokeweed mitogen (PWM)-stimulated cultures of human peripheral blood lymphocytes, while LTC4 and LTD4 have little activity in this system. Preincubation of T cells with LTB4 in nanomolar to picomolar concentrations rendered these cells suppressive of Ig production in subsequent PWM-stimulated cultures of fresh, autologous B + T cells. This LTB4-induced suppressor cell was radiosensitive, and its generation could be blocked by cyclohexamide but not by mitomycin C. The LTB4-induced suppressor cell was OKT8(+), while the precursor for the cell could be OKT8(-). The incubation of OKT8(-) T cells with LTB4 for 18 h resulted in the appearance of the OKT8(+) on 10-20% of the cells, and this could be blocked by cyclohexamide but not by mitomycin C. Thus, LTB4 in very low concentrations induces a radiosensitive OKT8(+) suppressor cell from OKT8(-) cells. In this regard, LTB4 is three to six orders of magnitude more potent than any endogenous hormonal inducer of suppressor cells previously described. Glucocorticosteroids, which block suppressor cell induction in many systems, may act by inhibiting endogenous production of LTB4

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

    Science.gov (United States)

    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.

  17. Inhibition of common cold-induced aggravation of childhood asthma by leukotriene receptor antagonists.

    Science.gov (United States)

    Yoshihara, Shigemi; Fukuda, Hironobu; Abe, Toshio; Nishida, Mitsuhiro; Yamada, Yumi; Kanno, Noriko; Arisaka, Osamu

    2012-09-01

    Virus infection is an important risk factor for aggravation of childhood asthma. The objective of this study was to examine the effect of drugs on aggravation of asthma induced by a common cold. Asthma control was examined in a survey of 1,014 Japanese pediatric patients with bronchial asthma. The occurrence of common cold, asthma control, and drugs used for asthma control were investigated using a modified Childhood Asthma Control Test (C-ACT) for patients aged cold and aggravation of asthma were significantly higher in patients aged cold-induced aggravation was significantly less effective in patients aged cold, asthma control was significantly more effective for those treated with leukotriene receptor antagonists (LTRAs) compared to treatment without LTRAs. Asthma control did not differ between patients who did or did not take inhaled corticosteroids or long-acting β2 stimulants. These findings showed a high prevalence of common cold in younger patients with childhood asthma and indicated that common cold can induce aggravation of asthma. LTRAs are useful for long-term asthma control in very young patients who develop an asthma attack due to a common cold.

  18. Gastric myoelectric activity during cisplatin-induced acute and delayed emesis reveals a temporal impairment of slow waves in ferrets: effects not reversed by the GLP-1 receptor antagonist, exendin (9-39).

    Science.gov (United States)

    Lu, Zengbing; Ngan, Man P; Lin, Ge; Yew, David T W; Fan, Xiaodan; Andrews, Paul L R; Rudd, John A

    2017-11-17

    Preclinical studies show that the glucagon-like peptide-1 (GLP-1) receptor antagonist, exendin (9-39), can reduce acute emesis induced by cisplatin. In the present study, we investigate the effect of exendin (9-39) (100 nmol/24 h, i.c.v), on cisplatin (5 mg/kg, i.p.)-induced acute and delayed emesis and changes indicative of 'nausea' in ferrets. Cisplatin induced 37.2 ± 2.3 and 59.0 ± 7.7 retches + vomits during the 0-24 (acute) and 24-72 h (delayed) periods, respectively. Cisplatin also increased ( P Advanced multifractal detrended fluctuation analysis revealed that the slow wave signal shape became more simplistic during delayed emesis. Cisplatin did not affect blood pressure (BP), but transiently increased heart rate, and decreased heart rate variability (HRV) during acute emesis; HRV spectral analysis indicated a shift to 'sympathetic dominance'. A hyperthermic response was seen during acute emesis, but hypothermia occurred during delayed emesis and there was also a decrease in HR. Exendin (9-39) did not improve feeding and drinking but reduced cisplatin-induced acute emesis by ~59 % ( P waves may represent a novel approach to treat the side effects of chemotherapy.

  19. Evaluation of domperidone as a modifier of gamma-radiation-induced emesis

    International Nuclear Information System (INIS)

    Cordts, R.E.; Yochmowitz, M.G.; Hardy, K.A.

    1987-01-01

    The D2 antidopaminergic drug domperidone was evaluated, singly and in combination with synthetic adrenocorticoid and an H2 antihistamine, for its ability to reduce the acute emetic effects of 60 Co whole-body radiation. Random-source adult male dogs were fasted 12 hr, fed a standard meal, injected 44 min later, and irradiated 47 min after that. Four groups of dogs were irradiated after drug injections as follows: saline (Con), domperidone (Dom), cimetidine + thiethylperazine (Cim + Thi), and dexamethasone + domperidone + cimetidine (Dex + Dom + Cim). Drug quantities given the dogs represented 10 mg Dom, 10 mg Thi, 20 mg Dex, and 300 mg Cim for an average human (70 kg, 1.8 m2). Subjects were exposed on an up-down schedule to determine the radiation necessary to produce vomiting in 50% (ED50) of each group. Emesis onset and offset times and number of episodes were recorded. The Dom group had more emetic episodes than any other. The Dex + Dom + Cim combination significantly raised the emetic threshold while maintaining episodes at a low incidence

  20. A possible role for cysteinyl-leukotrienes in non-ionic contrast media induced adverse reactions

    Energy Technology Data Exchange (ETDEWEB)

    Boehm, Ingrid [Department of Radiology, University of Bonn, Sigmund Freud Strasse 25, 53105 Bonn (Germany)]. E-mail: i.boehm@uni-bonn.de; Speck, Ulrich [Department of Radiology, Humboldt University (Charite) of Berlin (Germany); Schild, Hans [Department of Radiology, University of Bonn, Sigmund Freud Strasse 25, 53105 Bonn (Germany)

    2005-09-01

    Purpose: To test whether mono- or dimeric X-ray contrast media (CM) may induce the de novo production of cysteinyl-leukotriens (cys-LT), that could contribute to allergic/allergy-like side effects. Materials and methods: Leukocytes from 39 patients receiving iopromide or iotrolan for routine CT-examination were analyzed for the production of cys-LT. Histamine levels were analyzed in plasma specimens. One patient with a positive history of a previous CM-reaction did not receive CM-injection. Results: Three patients of the iopromide and five of the iotrolan group showed adverse reactions. Reactors had increased cys-LT values in samples obtained before CM-injection induced by the positive control (anti-Fc{epsilon}RI antibodies) (6763.7 pg/ml {+-} 1367.3 versus 2299.8 pg/ml {+-} 399.2; p < 0.007). Patients with versus without CM-reaction did not differ significantly with respect to their histamine values before CM-administeration. In vitro iopromide (p < 0.0002) and iotrolan (p < 0.0008) induced significant cys-LT production as compared to IL-3 stimulation. In vivo both CM induced a significant increase 6 h after CM administration (p < 0.05). Conclusion: Our findings suggest that both CM seem to induce cys-LT production. As to whether the observed increased values in pre-dose samples of patients with as compared to those without reactions could contribute to identify high risk patients should be investigated in larger patient groups in future.

  1. A possible role for cysteinyl-leukotrienes in non-ionic contrast media induced adverse reactions

    International Nuclear Information System (INIS)

    Boehm, Ingrid; Speck, Ulrich; Schild, Hans

    2005-01-01

    Purpose: To test whether mono- or dimeric X-ray contrast media (CM) may induce the de novo production of cysteinyl-leukotriens (cys-LT), that could contribute to allergic/allergy-like side effects. Materials and methods: Leukocytes from 39 patients receiving iopromide or iotrolan for routine CT-examination were analyzed for the production of cys-LT. Histamine levels were analyzed in plasma specimens. One patient with a positive history of a previous CM-reaction did not receive CM-injection. Results: Three patients of the iopromide and five of the iotrolan group showed adverse reactions. Reactors had increased cys-LT values in samples obtained before CM-injection induced by the positive control (anti-FcεRI antibodies) (6763.7 pg/ml ± 1367.3 versus 2299.8 pg/ml ± 399.2; p < 0.007). Patients with versus without CM-reaction did not differ significantly with respect to their histamine values before CM-administeration. In vitro iopromide (p < 0.0002) and iotrolan (p < 0.0008) induced significant cys-LT production as compared to IL-3 stimulation. In vivo both CM induced a significant increase 6 h after CM administration (p < 0.05). Conclusion: Our findings suggest that both CM seem to induce cys-LT production. As to whether the observed increased values in pre-dose samples of patients with as compared to those without reactions could contribute to identify high risk patients should be investigated in larger patient groups in future

  2. Prostaglandin E2/leukotriene B4 balance induced by Lutzomyia longipalpis saliva favors Leishmania infantum infection.

    Science.gov (United States)

    Araújo-Santos, Théo; Prates, Deboraci Brito; França-Costa, Jaqueline; Luz, Nívea F; Andrade, Bruno B; Miranda, José Carlos; Brodskyn, Claudia I; Barral, Aldina; Bozza, Patrícia T; Borges, Valéria Matos

    2014-12-20

    Eicosanoids and sand fly saliva have a critical role in the Leishmania infection. Here, we evaluated the effect of Lutzomyia longipalpis salivary gland sonicate (SGS) on neutrophil and monocyte recruitment and activation of eicosanoid production in a murine model of inflammation. C57BL/6 mice were inoculated intraperitonealy with Lutzomyia longipalpis SGS or Leishmania infantum or both, followed by analyses of cell recruitment, parasite load and eicosanoid production. Intraperitoneal injection of Lutzomyia longipalpis SGS together with Leishmania infantum induced an early increased parasite viability in monocytes and neutrophils. L. longipalpis SGS increased prostaglandin E2 (PGE2), but reduced leukotriene B4 (LTB4) production ex vivo in peritoneal leukocytes. In addition, the pharmacological inhibition of cyclooxygenase 2 (COX-2) with NS-398 decreased parasite viability inside macrophages during Leishmania infection in the presence of L. longipalpis SGS arguing that PGE2 production is associated with diminished parasite killing. These findings indicate that L. longipalpis SGS is a critical factor driving immune evasion of Leishmania through modulation of PGE2/LTB4 axis, which may represent an important mechanism on establishment of the infection.

  3. Concentrations of cysteinyl leukotrienes in urine and bronchoalveolar lavage fluid of cats with experimentally induced asthma.

    Science.gov (United States)

    Norris, Carol R; Decile, Kendra C; Berghaus, Londa J; Berghaus, Roy D; Walby, William F; Schelegle, Edward S; Hyde, Dallas M; Gershwin, Laurel J

    2003-11-01

    To evaluate changes in cysteinyl leukotriene (LT) concentrations in urine and bronchoalveolar lavage fluid (BALF) in cats with experimentally induced asthma. 19 cats with experimentally induced asthma and 5 control cats. Cats were sensitized to Bermuda grass or house dust mite allergen, and phenotypic features of asthma were confirmed with intradermal skin testing, evaluation of BALF eosinophil percentages, and pulmonary function testing. A competitive ELISA kit for LTC4, LTD4, and LTE4 was used for quantitative analysis of LTs. Urinary creatinine concentrations and BALF total protein (TP) concentrations were measured, and urinary LT-to-creatinine ratios and BALF LT-to-TP ratios were calculated. Mean urinary LT-to-creatinine ratios did not differ significantly between control cats and allergen-sensitized cats before or after sensitization and challenge exposure with saline (0.9% NaCl) solution or allergen, respectively. In BALF the mean LT-to-TP ratio of control cats did not differ significantly before or after sensitization and challenge exposure with saline. Asthmatic cats had BALF LT-to-TP ratios that were significantly lower than control cats at all time points, whereas ratios for asthmatic cats did not differ significantly among the various time points. Although LTs were readily detectable in urine, no significant increases in urinary LT concentrations were detected after challenge in allergen-sensitized cats. Spot testing of urinary LT concentrations appears to have no clinical benefit for use in monitoring the inflammatory asthmatic state in cats. The possibility that cysteinyl LTs bind effectively to their target receptors in BALF and, thus, decrease free LT concentrations deserves further study.

  4. Esculetin reduces leukotriene B4 level in plasma of rats with adjuvant-induced arthritis

    Directory of Open Access Journals (Sweden)

    Przemysław Rzodkiewicz

    2016-10-01

    Full Text Available Objectives : Esculetin (6,7-dihydroxycoumarin is a natural coumarin with anti-oxidant, anti-inflammatory and anti-nociceptive activity. It acts as a potent inhibitor of lipoxygenases (5-LOX and 12-LOX and decreases the production of matrix metalloproteinases (MMP-1, MMP-3 and MMP-9. Because both inhibition of lipoxygenases and inhibition of matrix metalloproteinases are effective strategies in the treatment of rheumatoid arthritis, we investigated whether esculetin may be effective in adjuvant-induced arthritis in rats. Material and methods : The study was performed on male Lewis rats, in the adjuvant-induced arthritis model. Rats were divided into two groups: control (treated with 1% methylcellulose and experimental (treated with esculetin – 10 mg/kg ip.. The tested compound was administered for 5 consecutive days starting on the 21st day after induction of arthritis. Each group consisted of 7 animals. After 5 days of treatment, rats were anesthetized. The concentration of leukotriene B4 (LTB4 in plasma was determined by a competitive enzyme immunoassay. Results : The LTB4 level in plasma of rats with adjuvant-induced arthritis is increased in comparison to rats without inflammation (362 ±34 vs. 274 ±15 pg/ml, p < 0.01, respectively. Five-day treatment with esculetin in adjuvant-induced arthritis rats decreases the LTB4 level to a level comparable with rats without inflammation (284 ±23 pg/ml, p < 0.01. Conclusions : LTB4 is the most potent chemotactic agent influencing neutrophil migration into the joint. It is known that its level in serum of patients with active rheumatoid arthritis is increased and correlates with disease severity. Some other lipoxygenase inhibitors have already been tested as potential drug candidates in clinical and preclinical trials for rheumatoid arthritis (Zileuton, PF-4191834. Because esculetin decreases the LTB4 level in plasma of rats in adjuvant-induced arthritis, it may also be considered as an attractive

  5. Role of the route of leukotrienes in an experimental model of oral mucositis induced by 5-fluorouracil 1.

    Science.gov (United States)

    Silva, Viviane Carvalho da; Leitão, Renata Ferreira de Carvalho; Brito, Gerly Anne de Castro; Martins, Conceição da Silva; Freire, Gildenio Estevam; Aragão, Karoline Saboia; Wanderley, Carlos Wagner de Souza; Freitas, Marcos Rabelo de

    2017-09-01

    To investigate the participation of cysteinyl leukotrienes in the pathophysiology of oral mucositis. Oral mucositis was induced in hamsters using 5-fluorouracil (5-FU; 60 and 40 mg/kg; i.p., on days 1 and 2, respectively, and with excoriations in jugal mucosa on day 4). Montelukast (10, 20, or 40 mg/kg/d; gavage), MK886 (3 mg/kg/d, i.p.), or saline or celecoxib (7.5 mg/kg/d; i.p.) was administered 1 h prior to 5-FU and daily, until the fourth (MK886) or tenth day, when the animals were euthanized and their jugal mucosa was collected for macroscopic, histopathological, and immunohistochemical evaluation. Neither montelukast nor MK-886 prevented the oral mucositis induced by 5-FU, as observed by histopathological evaluation. In addition, we did not find significant differences in the expression of inducible nitric oxide synthase-2, cyclooxygenase-2, or interleukin (IL)-1β between the experimental and control groups. However, we did observe a significant decrease in tumor necrosis factor (TNF)-α expression for all doses of montelukast; we also observed a significant decrease in IL-10 with 40 mg/kg/d and MK 886. Cysteinyl leukotrienes do not play an important role in experimental oral mucositis induced by 5-FU. There is a modulating action specifically on TNF-α.

  6. The inflammatory mediator leukotriene D4 induces subcellular β-catenin translocation and migration of colon cancer cells

    International Nuclear Information System (INIS)

    Salim, Tavga; Sand-Dejmek, Janna; Sjölander, Anita

    2014-01-01

    The abnormal activation of the Wnt/β-catenin pathway frequently occurs in colorectal cancer. The nuclear translocation of β-catenin activates the transcription of target genes that promote cell proliferation, survival, and invasion. The pro-inflammatory mediator leukotriene D 4 (LTD 4 ) exerts its effects through the CysLT 1 receptor. We previously reported an upregulation of CysLT 1 R in patients with colon cancer, suggesting the importance of leukotrienes in colon cancer. The aim of this study was to investigate the impact of LTD 4 on Wnt/β-catenin signaling and its effects on proliferation and migration of colon cancer cells. LTD 4 stimulation led to an increase in β-catenin expression, β-catenin nuclear translocation and the subsequent transcription of MYC and CCND1. Furthermore, LTD 4 significantly reduced the expression of E-cadherin and β-catenin at the plasma membrane and increased the migration and proliferation of HCT116 colon cancer cells. The effects of LTD 4 can be blocked by the inhibition of CysLT 1 R. Furthermore, LTD 4 induced the inhibition of glycogen synthase kinase 3 (GSK)-3β activity, indicating a crosstalk between the G-protein-coupled receptor CysLT 1 and the Wnt/β-catenin pathway. In conclusion, LTD 4 , which can be secreted from macrophages and leukocytes in the tumor microenvironment, induces β-catenin translocation and the activation of β-catenin target genes, resulting in the increased proliferation and migration of colon cancer cells. - Highlights: • Leukotriene D 4 (LTD 4 ) lowers membrane β-catenin but increases nuclear β-catenin levels in colon cancer cells. • In agreement, LTD 4 triggers inactivation of GSK-3β, activation of TCF/LEF and increased expression of Cyclin D1 and c-Myc. • LTD 4 also caused a significant reduction in the expression of E-cadherin and an increased migration of colon cancer cells

  7. The inflammatory mediator leukotriene D{sub 4} induces subcellular β-catenin translocation and migration of colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Salim, Tavga [Division of Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Clinical Research Center, Skåne University Hospital, Malmö (Sweden); Sand-Dejmek, Janna [Division of Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Clinical Research Center, Skåne University Hospital, Malmö (Sweden); Section of Surgery, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö (Sweden); Bayer HealthCare, Pharmaceuticals Medical Affairs, Solna (Sweden); Sjölander, Anita, E-mail: anita.sjolander@med.lu.se [Division of Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Clinical Research Center, Skåne University Hospital, Malmö (Sweden)

    2014-02-15

    The abnormal activation of the Wnt/β-catenin pathway frequently occurs in colorectal cancer. The nuclear translocation of β-catenin activates the transcription of target genes that promote cell proliferation, survival, and invasion. The pro-inflammatory mediator leukotriene D{sub 4} (LTD{sub 4}) exerts its effects through the CysLT{sub 1} receptor. We previously reported an upregulation of CysLT{sub 1}R in patients with colon cancer, suggesting the importance of leukotrienes in colon cancer. The aim of this study was to investigate the impact of LTD{sub 4} on Wnt/β-catenin signaling and its effects on proliferation and migration of colon cancer cells. LTD{sub 4} stimulation led to an increase in β-catenin expression, β-catenin nuclear translocation and the subsequent transcription of MYC and CCND1. Furthermore, LTD{sub 4} significantly reduced the expression of E-cadherin and β-catenin at the plasma membrane and increased the migration and proliferation of HCT116 colon cancer cells. The effects of LTD{sub 4} can be blocked by the inhibition of CysLT{sub 1}R. Furthermore, LTD{sub 4} induced the inhibition of glycogen synthase kinase 3 (GSK)-3β activity, indicating a crosstalk between the G-protein-coupled receptor CysLT{sub 1} and the Wnt/β-catenin pathway. In conclusion, LTD{sub 4}, which can be secreted from macrophages and leukocytes in the tumor microenvironment, induces β-catenin translocation and the activation of β-catenin target genes, resulting in the increased proliferation and migration of colon cancer cells. - Highlights: • Leukotriene D{sub 4} (LTD{sub 4}) lowers membrane β-catenin but increases nuclear β-catenin levels in colon cancer cells. • In agreement, LTD{sub 4} triggers inactivation of GSK-3β, activation of TCF/LEF and increased expression of Cyclin D1 and c-Myc. • LTD{sub 4} also caused a significant reduction in the expression of E-cadherin and an increased migration of colon cancer cells.

  8. Food restriction, refeeding, and gastric fill fail to affect emesis in musk shrews

    OpenAIRE

    Horn, Charles C.; Still, Liz; Fitzgerald, Christiana; Friedman, Mark I.

    2009-01-01

    Nausea and emesis are common side effects of gastrointestinal disease. Reports indicate that ghrelin and endocannabinoids, agents that stimulate appetite, also reduce emesis evoked by chemotherapy treatment, which suggests that stimulation of feeding inhibits the emetic system. In the following study we conducted a more direct test of this hypothesis by determining the impact of manipulating the motivation to eat on emesis, using food restriction and refeeding. Emesis was induced in musk shre...

  9. Efficacy of ondansetron in the management of radiotherapy induced emesis: a review. Efficacite de l'ondansetron dans les nausees et vomissements radio-induits: revue de la litterature

    Energy Technology Data Exchange (ETDEWEB)

    Levy, E. (Hopital Henri-Mondor, 94 - Creteil (France)); Paillarse, J.M.; Votan, B. (Laboratoires Glaxo, 75 - Paris (France))

    1994-01-01

    Radiotherapy-induced emesis depends on the site of irradiation, the field size and the dose per fraction and is generally less intense than chemotherapy-induced emesis. Established anti-emetic drugs offer only limited symptom control (50%). Ondansetron, a 5HT[sub 3] receptors antagonist, had proven a complete or a major control efficacy (0-2 emetic episodes) of 68 to 95% in three pilot studies (fractionated, single-dose and total body irradiations). In controlled studies, ondansetron efficacy was significantly higher than placebo, metoclopramide and prochlorperazine. The treatment was well tolerated in the different studies. (authors). 23 refs., 2 figs., 1 tab.

  10. Ligand-induced tyrosine phosphorylation of cysteinyl leukotriene receptor 1 triggers internalization and signaling in intestinal epithelial cells

    DEFF Research Database (Denmark)

    Parhamifar, Ladan; Sime, Wondossen; Yudina, Yuliana

    2010-01-01

    Leukotriene D(4) (LTD(4)) belongs to the bioactive lipid group known as eicosanoids and has implications in pathological processes such as inflammation and cancer. Leukotriene D(4) exerts its effects mainly through two different G-protein-coupled receptors, CysLT(1) and CysLT(2). The high affinit...

  11. Development of a model system to study leukotriene-induced modification of radiation sensitivity in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Walden, Jr, T L; Holahan, Jr, E V; Catravas, G N

    1986-01-01

    Leukotrienes (LT) are an important class of biological mediators for which no information exists concerning their synthesis following a radiation insult or on their ability to modify cellular response to a subsequent radiation exposure. Results are presented which illustrate that the Chinese hamster lung fibroblast cell line, V79A03, is useful as a model system to study the metabolic fate of leukotrienes and the effect of LT on radiation sensitivity of mammalian cells in vitro. (U.K.).

  12. Delta-9-tetrahydrocannabinol differentially suppresses cisplatin-induced emesis and indices of motor function via cannabinoid CB(1) receptors in the least shrew.

    Science.gov (United States)

    Darmani, N A

    2001-01-01

    We have recently shown that the cannabinoid CB(1) receptor antagonist, SR 141716A, produces emesis in the least shrew (Cryptotis parva) in a dose- and route-dependent manner. This effect was blocked by delta-9-tetrahydrocannabinol (Delta(9)-THC). The present study investigates the cannabinoid receptor mechanisms by which Delta(9)-THC produces its antiemetic effects against cisplatin (20 mg/kg, i.p.)-induced emesis as well as its cannabimimetic activity profile (motor reduction) in the least shrew. Intraperitoneal administration of Delta(9)-THC (1, 2.5, 5 and 10 mg/kg) dose-dependently reduced both the percentage of animals vomiting (ID(50)=1.8+/-1.6 mg/kg) and the frequency of vomits (ID(50)=0.36+/-1.18 mg/kg) in a potent manner. The lowest significantly effective antiemetic dose of Delta(9)-THC for the latter emesis parameters was 2.5 mg/kg. Although Delta(9)-THC reduced the frequency of vomits up to 98%, it failed to completely protect all tested shrews from vomiting (80% protection). The cannabinoid CB(1) antagonist (SR 141716A) and not the CB(2) antagonist (SR 144528), reversed the antiemetic effects of Delta(9)-THC in a dose-dependent fashion. Delta(9)-THC (1, 5, 10 and 20 mg/kg, ip) suppressed locomotor parameters (spontaneous locomotor activity, duration of movement and rearing frequency) in a biphasic manner and only the 20-mg/kg dose simultaneously suppressed the triad of locomotor parameters to a significant degree. Subcutaneous (1-10 mg/kg) and intraperitoneal (0.05-40 mg/kg) injection of some doses of SR 141716A caused significant reductions in one or more components of the triad of locomotor parameters but these reductions were not dose dependent. Subcutaneous injection of SR 141716A (0.2, 1, 5 and 10 mg/kg) reversed the motor suppressant effects of a 20-mg/kg dose of Delta(9)-THC (ip) in a dose-dependent manner. Relative to its motor suppressant effects, Delta(9)-THC is a more potent antiemetic agent. Both effects are probably mediated via CB(1

  13. Total body irradiation prior to bone marrow transplantation: efficacy and safety of granisetron in the prophylaxis and control of radiation-induced emesis

    International Nuclear Information System (INIS)

    Belkacemi, Yazid; Ozsahin, Mahmut; Pene, Francoise; Rio, Bernard; Sutton, Laurent; Laporte, Jean-Philippe; Touboul, Emmanuel; Gorin, Norbert-Claude; Laugier, Alain

    1996-01-01

    moderate nausea; S3 = severe nausea and/or single episode of vomiting; and S4 multiple episodes of vomiting. Results: During TBI, 18 (50%) patients were scored as complete responders (S1), 1 (3%) as a major responder (S2), 9 (25%) as minor responders (S3), and 8 (22%) as nonresponders (S4). During the following 12 h, 28 (78%) patients were free of severe nausea and vomiting (S1 or S2), whereas 8 (22%) vomited (S3 or S4). In univariate analyses, the 12-h probability of emesis was significantly higher in patients undergoing hyper diuresis (63% vs. 30%; p = 0.05), and in patients older than 45 years (65% for age >45 vs. 33% for age ≤45; p = 0.05). The probability of S3 or S4 emesis was 50% with Treatment A and 47% with Treatment B (p = 0.86). Sex, body weight, and type of conditioning chemotherapy did not influence the 12-h probability of emesis. Multivariate analysis revealed that hyper diuresis (p 0.02) and Treatment A (p = 0.04) were independently associated with radiation-induced emesis, whereas sex (p = 0.85), body weight (p = 0.13), age (p = 0.12), and type of conditioning chemotherapy (p = 0.92) were not. No early toxicity related to granisetron was observed. Conclusion: Granisetron is a well-tolerated and effective antiemetic agent that can be used as monotherapy during single-dose TBI. Good control of nausea and vomiting is obtained with this antiemetic drug, and its effect is increased when hyper diuresis is suspended during TBI

  14. Evaluation of the Efficacy of Aprepitant on the Prevention of Chemotherapy-Induced Nausea and Vomiting and Quality of Life with Functional Living Index Emesis

    Directory of Open Access Journals (Sweden)

    Görkem Aksu

    2013-03-01

    Full Text Available Objective: Functional Living Index Emesis (FLIE is developed to evaluate the relationship between emesis and it's effects on patient's daily life and is far more relevant to detect the effectiveness of antiemetic treatment compared with self-diary reports. In this study, the efficacy of oral neurokinin-1 antagonist aprepitant on the prevention of chemotherapy-induced nausea and vomiting and quality of life is evaluated with FLIE. Study Design: Cross sectional study. Material and Methods: Sixty patients with Non-Small Cell Lung Cancer (NSCLC receiving a chemotherapy regimen consisting of Cisplatin and Docetaxel were evaluated. The patients were prospectively randomized to two groups before the first cycle of chemotherapy. Patients in Group A (31 patients received 3 daily doses of aprepitant along with oral ondansetron and dexamethasone. The patients in group B (29 patients received only ondansetron and dexamathasone. The efficacy of both regimens was evaluated by a modified Turkish version of FLIE scale consisting of 18 questions. Results: The number of patients with complete response was 31 in the whole group. Of these 18 patients (58% were in Group A (Aprepitant and 13 patients in group B (42%. Median FLIE score in group A was 24.97 (±12.45 while it was 38.1 (±26.987 in group B and the difference was statistically significant (p=0.022. Total score >20 was seen in only 5 of 31 patients in aprepitant group (16% showing the significant efficiency of aprepitant on quality of life, while in group B, 13 of 29 patients (44% had total scores >20 (p=0.02. Conclusion: Regarding these findings, it is certain to state that aprepitant in combination with other drugs optimizes protection against both nausea and vomiting compared to the prior standard of care, and must be recommended as first-line therapy for patients who are treated with moderately or highly emetogenic chemotherapy.

  15. Acute emesis: moderately emetogenic chemotherapy

    DEFF Research Database (Denmark)

    Herrstedt, Jørn; Rapoport, Bernardo; Warr, David

    2011-01-01

    This paper is a review of the recommendations for the prophylaxis of acute emesis induced by moderately emetogenic chemotherapy as concluded at the third Perugia Consensus Conference, which took place in June 2009. The review will focus on new studies appearing since the Second consensus conference...... receiving multiple cycles of moderately emetogenic chemotherapy will be reviewed. Consensus statements are given, including optimal dose and schedule of serotonin(3) receptor antagonists, dexamethasone, and neurokinin(1) receptor antagonists. The most significant recommendations (and changes since the 2004...... version of the guidelines) are as follows: the best prophylaxis in patients receiving moderately emetogenic chemotherapy (not including a combination of an anthracycline plus cyclophosphamide) is the combination of palonosetron and dexamethasone on the day of chemotherapy, followed by dexamethasone...

  16. Inhibition of Common Cold-Induced Aggravation of Childhood Asthma by Leukotriene Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Shigemi Yoshihara

    2012-01-01

    Conclusions: : These findings showed a high prevalence of common cold in younger patients with childhood asthma and indicated that common cold can induce aggravation of asthma. LTRAs are useful for long-term asthma control in very young patients who develop an asthma attack due to a common cold.

  17. Inhibition of Common Cold-Induced Aggravation of Childhood Asthma by Leukotriene Receptor Antagonists

    OpenAIRE

    Shigemi Yoshihara; Hironobu Fukuda; Toshio Abe; Mitsuhiro Nishida; Yumi Yamada; Noriko Kanno; Osamu Arisaka

    2012-01-01

    Background: : Virus infection is an important risk factor for aggravation of childhood asthma. The objective of this study was to examine the effect of drugs on aggravation of asthma induced by a common cold. Methods: : Asthma control was examined in a survey of 1,014 Japanese pediatric patients with bronchial asthma. The occurrence of common cold, asthma control, and drugs used for asthma control were investigated using a modified Childhood Asthma Control Test (C-ACT) for patients aged

  18. Endogenous leukotriene formation during anaphylactic shock

    International Nuclear Information System (INIS)

    Keppler, A.; Oerning, L.; Bernstroem, K.; Hammarstroem, S.

    1987-01-01

    Leukotriene (LT)C 4 is a biologically active substance, presumed to play major roles as a mediator of allergic and anaphylactic reactions. It is formed e.g. by basophilic and eosinophilic leukocytes, monocytes, macrophages, and mast cells. In cells having IgE receptors, bridging of these by divalent anti-IgE-receptor antibodies or by interaction between receptor-bound IgE and anti-IgE will induce LTC 4 formation. Leukotriene formation has also been demonstrated in other in vitro models of immediate hypersensivity. The biological actions of LTC 4 , comprise induction of airway obstruction, constriction of coronary arteries, hypotension, and plasma extravasation. Leukotriene formation in vivo may mediate anaphylactic shock symptoms and cause the death of an animal. In order to prove the presumed mediator role of this substance in anaphylactic reactions, it is necessary to demonstrate its endogenous formation during shock. Studies on the metabolism of LTC 4 have revealed rapid catabolism by various transformations of the peptide substituent. Recently, three metabolites were demonstrated to be excreted as end-products in man (LTE 4 ,) and the rat (N-acetyl LTE 4 and N-acetyl 11-trans LTE 4 ). By monitoring biliary N-acetyl LTE 4 levels, endogenous leukotriene formation in the rat was demonstrated in vivo after tissue trauma and endotoxin shock. We now wish to report evidence for endogenous leukotriene C 4 production during anaphylactic shock in guinea pigs. 37 refs. (author)

  19. The anti-inflammatory effect of montelukast, a cysteinyl leukotriene receptor-1 antagonist, against estradiol-induced nonbacterial inflammation in the rat prostate.

    Science.gov (United States)

    Said, Mahmoud M; Bosland, Maarten C

    2017-02-01

    There is no standard treatment of chronic nonbacterial prostatitis in humans. The current study was aimed to investigate the effect of montelukast, an antagonist of cysteinyl leukotriene receptor-1, against estrogen-induced, nonbacterial lateral lobe-specific prostate inflammation in rats. Male Wistar rats were randomized into five groups of six rats, including sham controls (group 1) and castrated rats (group 2), whereas nonbacterial prostatitis (NBP) was induced in groups 3-5 by castration followed by a daily subcutaneous injection of estradiol (0.25 mg/kg body weight) for 30 days. The rats were left otherwise untreated (group 3) or received a daily oral administration of montelukast (1 and 10 mg/kg body weight for groups 4 and 5, respectively) from the 17th day after castration for two consecutive weeks. Compared with sham controls, induction of NBP led to a significant increase in serum leukotriene B 4 (LTB4), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) levels, along with a significant upregulation in the transcript level of proinflammatory molecules (nuclear factor kappa beta [NF-κβ] and inducible nitric oxide synthase [iNOS]), chemokines (monocyte chemoattractant protein-1 [MCP-1] and eotaxin), and E-selectin in the lateral prostate. Histological examination revealed intense inflammation in the prostate with leukocyte infiltration and acinar degeneration following estradiol treatment of castrated rats. Montelukast significantly suppressed the increase in serum and prostate proinflammatory mediators/chemokines expression and abolished the histologically inflammatory changes in the lateral prostate. These findings indicate that montelukast inhibits estradiol-induced NBP in a rat model through anti-inflammatory mechanisms, suggesting its future beneficial effect for the treatment of clinical chronic NBP.

  20. Impact of arachidonic versus eicosapentaenoic acid on exotonin-induced lung vascular leakage: relation to 4-series versus 5-series leukotriene generation.

    Science.gov (United States)

    Grimminger, F; Wahn, H; Mayer, K; Kiss, L; Walmrath, D; Seeger, W

    1997-02-01

    Escherichia coli hemolysin (HlyA) is a proteinaceous pore-forming exotoxin that is implicated as a significant pathogenicity factor in extraintestinal E. coli infections including sepsis. In perfused rabbit lungs, subcytolytic concentrations of the toxin evoke thromboxane-mediated vasoconstriction and prostanoid-independent protracted vascular permeability increase (11). In the present study, the influence of submicromolar concentrations of free arachidonic acid (AA) and eicosapentaenoic acid (EPA) on the HlyA-induced leakage response was investigated. HlyA at concentration from 0.02 to 0.06 hemolytic units/ml provoked a dose-dependent, severalfold increase in the capillary filtration coefficient (Kfc), accompanied by the release of leukotriene(LT)B4, LTC4, and LTE4 into the recirculating buffer fluid. Simultaneous application of 100 nmol/L AA markedly augmented the HlyA-elicited leakage response, concomitant with an amplification of LTB4 release and a change in the kinetics of cysteinyl-LT generation. In contrast, 50 to 200 nmol/L EPA suppressed in a dose-dependent manner the HlyA-induced increase in Kfc values. This was accompanied by a blockage of 4-series LT generation and a dose-dependent appearance of LTB5, LTC5, and LTE5. In addition, EPA fully antagonized the AA-induced amplification of the HlyA-provoked Kfc increase, again accompanied by a shift from 4-series to 5-series LT generation. We conclude that the vascular leakage provoked by HlyA in rabbit lungs is differentially influenced by free AA versus free EPA, related to the generation of 4- versus 5-series leukotrienes. The composition of lipid emulsions used for parenteral nutrition may thus influence inflammatory capillary leakage.

  1. A randomized double-blind trial to compare the clinical efficacy of granisetron with metoclopramide, both combined with dexamethasone in the prophylaxis of chemotherapy-induced delayed emesis

    OpenAIRE

    Aapro, M. S.; Thuerlimann, B.; Sessa, C.; de Pree, C.; Bernhard, J.; Maibach, R.

    2017-01-01

    Background: The prophylactic use of 5-HT3 receptor antagonists (setrons), after the first 24 h (acute phase) of exposure to emetic chemotherapy, to decrease the incidence of ‘delayed phase' emesis increases costs. We designed a study to evaluate the efficacy of a setron (granisetron) in the delayed phase, compared with metoclopramide, each combined with a corticosteroid. Patients and methods: Patients on their first course of single-day emetic chemotherapy (cisplatin, carboplatin, doxorubicin...

  2. Leukotriene B4 induces EMT and vimentin expression in PANC-1 pancreatic cancer cells: Involvement of BLT2 via ERK2 activation.

    Science.gov (United States)

    Kim, You Ri; Park, Mi Kyung; Kang, Gyeong Jin; Kim, Hyun Ji; Kim, Eun Ji; Byun, Hyun Jung; Lee, Moo-Yeol; Lee, Chang Hoon

    2016-12-01

    Leukotriene B 4 (LTB 4 ) is a leukocyte chemoattractant and plays a major role controlling inflammatory responses including pancreatitis. LTB 4 is known to be correlated with cancer progression. LTB 4 induces keratin phosphorylation and reorganization by activating extracellular regulated kinase (ERK) in PANC-1 pancreatic cancer cell lines. However, the role of LTB 4 in epithelial mesenchymal transition (EMT) and vimentin expression in pancreatic cancer cells is unknown. We examined whether LTB 4 induces EMT and vimentin expression by Western blot, si-RNA, and RT-PCR. LTB 4 induced morphological change, decreased E-cadherin expression and increased N-cadherin and vimentin expression. LTB4 increased migration and invasion of PANC-1 cancer cells. LTB 4 dose-dependently upregulated expression of vimentin in PANC-1 cancer cells. LTB 4 -induced vimentin expression was suppressed by LY255283 (BLT2 antagonist). Comp A, a BLT2 agonist, further increased vimentin expression. Gene silencing of BLT2 suppressed LTB 4 -or Comp A-induced vimentin expression in PANC-1 cells. The MEK inhibitor, PD98059 suppressed Comp A-induced vimentin expression. Comp A or transfection of plasmid containing BLT2 cDNA (pC BLT2 ) activated ERK, and BLT2 gene silencing suppressed Comp A-induced ERK activation. ERK2 siRNA abrogated Comp A-induced vimentin expression and ERK2 overexpression enhanced vimentin expression. One of well-known cause of ras mutation, cigarette smoke extracts increased BLT2 expression in PANC-1 cancer cells. Taken together, these results suggest that BLT2 is involved in LTB 4 -induced vimentin expression through ERK2 in PANC-1 cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Leukotrienes and leukotriene modifiers in pediatric allergic diseases

    African Journals Online (AJOL)

    Ehab

    ... 12(1):3-12. 3. Leukotrienes and leukotriene modifiers in pediatric allergic diseases ... childhood allergic diseases. This review ... produce cysteinyl-LTs and LTB4 spontaneously in vitro.8. Although nonleukocyte cells generally do not have sufficient 5-LO and FLAP to synthesize .... uninterrupted sleep in these patients.55.

  4. Neurokinin-1 receptor blocker CP-99 994 improved emesis induced by cisplatin via regulating the activity of gastric distention responsive neurons in the dorsal motor nucleus of vagus and enhancing gastric motility in rats.

    Science.gov (United States)

    Sun, X; Xu, L; Guo, F; Luo, W; Gao, S; Luan, X

    2017-10-01

    Nowadays, chemotherapy induced nausea and vomiting (CINV) is still common in patients with cancer. It was reported that substance P mediated CINV via neurokinin-1 (NK 1 ) receptor and antagonists of NK 1 receptor has been proved useful for treating CINV but the mechanism are not fully understood. This study aimed to examine the role of NK 1 receptor blocker, CP-99 994, when administrated into dorsal motor nucleus of vagus (DMNV), on the cisplatin-induced emesis in rats and the possible mechanism. Rats' kaolin intake, food intake, and bodyweight were recorded every day; gastric contraction activity was recorded in conscious rats through a force transducer implanted into the stomach; gastric emptying was monitored using the phenol red method; single unit extracellular firing in the DMNV were recorded. DMNV microinjection of CP-99 994 reduced the changes of increased kaolin consumption and suppressed food intake in cisplatin-treated rats; enhanced the gastric contraction activity dose-dependently in control and cisplatin-treated rats but enhanced gastric emptying only in cisplatin-treated rats; reduced the firing rate of gastric distention inhibited (GD-I) neurons but increased the firing rate of GD excited (GD-E) neurons in the DMNV. The effects of CP-99 994 on gastric motility and neuronal activity were stronger in cisplatin-treated rats than those of control rats. Our results suggested that CP-99 994 could improve emesis induced by cisplatin by regulating gastric motility and gastric related neuronal activity in the DMNV. © 2017 John Wiley & Sons Ltd.

  5. Leukotriene D4 induces chemotaxis in human eosinophilc cell line, EoL-1 cells via CysLT1 receptor activation.

    Science.gov (United States)

    Shirasaki, Hideaki; Kanaizumi, Etsuko; Himi, Tetsuo

    2017-11-01

    Numerous reports have shown that cysteinyl leukotrienes (CysLTs) contribute to tissue accumulation of eosinophils in allergic airway inflammation. To date, only a few studies have reported that CysLTs promote chemotactic activity of human eosinophils in vitro. The purpose of this study was to investigate whether CysLTs promote chemotaxis in the human eosinophilic cell line, EoL-1. EoL-1 cells were induced to differentiate into mature eosinophil-like cells via incubation with butyric acid and cytokines (IL-3, IL-5 and GM-CSF). The chemotactic activity of the differentiated EoL-1 cells was assessed using the commercial cell migration assay kit. LTD 4 elicited dose-related chemotactic activity in the differntiated EoL-1 cells in the range of 1-100 nM. A typical bell-shaped dose-response curve was observed with optimal activity at 10 nM. The chemotactic activity elicited by LTD 4 (10 nM) was significantly inhibited by montelukast (control, 345 ± 19.2 × 10 3 RFU; LTD 4 10 nM alone, 511 ± 39.2 × 10 3 RFU; LTD 4 10 nM plus montelukast 100 nM, 387 ± 28.2 × 10 3 RFU). LTD 4 induces migration in eosinophilic cells via activation of CysLT1 receptor. The present in vitro model may be useful for elucidation of the mechanism underlying CysLT-induced tissue eosinophilia.

  6. Prevention of radiation emesis in dogs by combinations of drugs

    International Nuclear Information System (INIS)

    Mattsson, J.L.; Cordts, R.E.; Yochmowitz, M.G.; Hardy, K.A.

    1984-01-01

    Male mixed-breed dogs were used to evaluate the effectiveness of cimetidine (Cim), promethazine (Pro), and thiethylperazine (Thi), singly and in combination, to raise the threshold for radiation-induced emesis. Cim was chosen as an H 2 antihistamine, Pro as an H 1 antihistamine, and Thi as a phenothiazine derivative dopamine blocker. Doses were calculated to approximate doses for an average human. Exposure was to 60 Co at 60 rad (midline) per min. The dogs were fed 0.4 kg canned dog food 1 hour before exposure, and injected with the appropriate drugs 30 minutes prior to exposure. Emesis onset times, number of episodes, and time to last episode were recorded. The radiation dose (midline tissue rad) to cause a 50% incidence of emesis (ED 50 ) was calculated using an up-and-down procedure. The ED 50 were: 258 (212-315) for controls; 240 (151-380) for Cim; 313 (256-384) for Pro; 405 (319-514) for Thi; 334 (284-394) for Cim + Pro; 446 (365-546) for Cim + Thi; 347 (306-399) for Pro + Thi; and 478 (428-539) for Cim + Pro + Thi

  7. Leukotriene B4 (LTB4) induces formation of inositol-phosphates (IP's) in rat peritoneal polymorphonuclear leukocytes (PMN's)

    International Nuclear Information System (INIS)

    Chi-Rosso, G.; Crooke, S.T.; Mong, S.

    1986-01-01

    LTB 4 induced rapid breakdown of prelabeled inositol-phospholipids (PI) in rat PMN. Formation of [ 3 H]-inositol-trisphosphate ([ 3 H]-IP 3 ) was rapid, with a peak of 250-300% of the control level, after 5-15 sec of stimulation with LTB 4 . Accumulation of [ 3 H]-inositol-bisphosphate ([ 3 H]-IP 2 ) was rapid, peaking after 30 sec of stimulation. [ 3 H]-inositol-monophosphate ([ 3 H]-IP 1 ) accumulated gradually in the presence of LiCl. The kinetics of [ 3 H]-IP 3 , [ 3 H]-IP 2 and [ 3 H]-IP 1 accumulation suggested that LTB 4 may interact with receptors in PMNs, activate phospholipase C which, in turn, induces hydrolysis of PI. The agonist activities of several LTB 4 analogs were employed to investigate the structure activity relationship of LTB 4 receptor mediated activation of PI hydrolysis. Increases in [ 3 H]-IP 3 formation were dependent upon the concentration of LTB 4 and the agonist analogs. The rank order potency of these analogs were equivalent to that of the pharmacological activity of LTB 4 agonists in the chemotaxis assay. Furthermore, the Islet activation protein (IAP) inhibited LTB 4 induced [ 3 H]-IP 3 formation. The tumor promoting phorbomyristate ester also inhibited LTB 4 induced [ 3 H]-IP 3 formation. These results suggest LTB 4 may interact with receptors in rat PMNs, activate G/sub i/ protein regulated phospholipase C and induce [ 3 H]-IP 3 formation

  8. Can treatment with Cocculine improve the control of chemotherapy-induced emesis in early breast cancer patients? A randomized, multi-centered, double-blind, placebo-controlled Phase III trial

    Directory of Open Access Journals (Sweden)

    Pérol David

    2012-12-01

    Full Text Available Abstract Background Chemotherapy induced nausea and vomiting (CINV remains a major problem that seriously impairs the quality of life (QoL in cancer patients receiving chemotherapy regimens. Complementary medicines, including homeopathy, are used by many patients with cancer, usually alongside with conventional treatment. A randomized, placebo-controlled Phase III study was conducted to evaluate the efficacy of a complex homeopathic medicine, Cocculine, in the control of CINV in non-metastatic breast cancer patients treated by standard chemotherapy regimens. Methods Chemotherapy-naïve patients with non-metastatic breast cancer scheduled to receive 6 cycles of chemotherapy including at least three initial cycles of FAC 50, FEC 100 or TAC were randomized to receive standard anti-emetic treatment plus either a complex homeopathic remedy (Cocculine, registered in France for treatment of nausea and travel sickness or the matching placebo (NCT00409071 clinicaltrials.gov. The primary endpoint was nausea score measured after the 1st chemotherapy course using the FLIE questionnaire (Functional Living Index for Emesis with 5-day recall. Secondary endpoints were: vomiting measured by the FLIE score, nausea and vomiting measured by patient self-evaluation (EVA and investigator recording (NCI-CTC AE V3.0 and treatment compliance. Results From September 2005 to January 2008, 431 patients were randomized: 214 to Cocculine (C and 217 to placebo (P. Patient characteristics were well-balanced between the 2 arms. Overall, compliance to study treatments was excellent and similar between the 2 arms. A total of 205 patients (50.9%; 103 patients in the placebo and 102 in the homeopathy arms had nausea FLIE scores > 6 indicative of no impact of nausea on quality of life during the 1st chemotherapy course. There was no difference between the 2 arms when primary endpoint analysis was performed by chemotherapy stratum; or in the subgroup of patients with susceptibility

  9. Bronchoprotection with a leukotriene receptor antagonist in asthmatic preschool children

    DEFF Research Database (Denmark)

    Bisgaard, H; Nielsen, K G

    2000-01-01

    We hypothesized that a leukotriene receptor antagonist (LTRA) could provide bronchoprotection against the cold, dry air-induced response in asthmatic preschool children. In a randomized, double-blind, placebo-controlled crossover study, we examined the effect of the specific LTRA montelukast at 5...

  10. Simultaneous initiation of degranulation and inhibition of leukotriene release by soman in human basophils

    Energy Technology Data Exchange (ETDEWEB)

    Meier, H.L.; Warner, J.; MacGlashan, D.W.

    1995-12-31

    Previous studies noted that the serine esterase inhibitor, soman, could induce histamine release from human basophils. To investigate the mechanisms by which soman causes histamine release (a preformed mediator), we also examined its ability to induce leukotriene release (a newly synthesized mediator) from basophils. We found that no leukotriene release followed activation with soman, while histamine release was usually greater than 70%. In addition, soman and diisopropyl-fluorophosphate were found actively to suppress low level spontaneous leukotriene release as well as ongoing leukotriene release induced by anti-IgE antibody. Soman (0.3 mM) was able to stop leukotriene release as rapidly as the calcium chelator, EDTA. In a series of control experiments, it was noted that soman did not influence the metabolism of LTC4 to LTD4 or LTE4 (for which little metabolism occurred), eliminating the possibility that reduced LTC4 release could have resulted from its enhanced metabolism. Therefore, using one compound (soman), basophils could be simultaneously activated to degranulate while having the pathway leading to leukotriene release actively suppressed. These results provide further evidence that histamine and leukotriene release are independent pathways resulting from the activation of basophils.

  11. Delayed emesis: moderately emetogenic chemotherapy (single-day chemotherapy regimens only)

    DEFF Research Database (Denmark)

    Roila, Fausto; Warr, David; Aapro, Matti

    2011-01-01

    An update of the recommendations for the prophylaxis of delayed emesis induced by moderately emetogenic chemotherapy discussed during the third Perugia Consensus Conference (June 2009) sponsored by MASCC-ESMO was presented. The review considered new studies published since the second consensus...

  12. Role of leukotrienes in asthma pathophysiology

    DEFF Research Database (Denmark)

    Bisgaard, H

    2000-01-01

    Inflammation is an essential component of asthma pathophysiology. While beta(2)-agonists are often used for short-term relief of acute bronchospasm, anti-inflammatory agents are required for the long-term management of chronic inflammation in this disease. Corticosteroids have emerged as the first......-line anti-inflammatory therapy for asthma management. However, in some patients, especially children, the high doses of corticosteroids that may be required to control features of hyperresponsiveness, including exercise-induced asthma, raise safety concerns. Thus, there is a need for complementary anti......-inflammatory, steroid-sparing agents in asthma therapy. Several inflammatory mediators have been targeted in an attempt to thwart this inflammatory process, but so far with little success. The cysteinyl leukotrienes (CysLT), LTC(4), LTD(4), and LTE(4), have been shown to be essential mediators in asthma, making them...

  13. Plant Natural Products Calycosin and Gallic Acid Synergistically Attenuate Neutrophil Infiltration and Subsequent Injury in Isoproterenol-Induced Myocardial Infarction: A Possible Role for Leukotriene B4 12-Hydroxydehydrogenase?

    Science.gov (United States)

    Cheng, Yuanyuan; Tse, Hung Fat; Le, X. Chris; Rong, Jianhui

    2015-01-01

    Leukotriene B4 12-hydroxydehydrogenase (LTB4DH) catalyzes the oxidation of proinflammatory LTB4 into less bioactive 12-oxo-LTB4. We recently discovered that LTB4DH was induced by two different natural products in combination. We previously isolated gallic acid from Radix Paeoniae through a bioactivity-guided fractionation procedure. The purpose of this study is to test the hypothesis that LTB4DH inducers may suppress neutrophil-mediated inflammation in myocardial infarction. We first isolated the active compound(s) from another plant, Radix Astragali, by the similar strategy. By evaluating LTB4DH induction, we identified calycosin and formononetin from Radix Astragali by HPLC-ESI-MS technique. We confirmed that gallic acid and commercial calycosin or formononetin could synergistically induce LTB4DH expression in HepG2 cells and human neutrophils. Moreover, calycosin and gallic acid attenuated the effects of LTB4 on the survival and chemotaxis of neutrophil cell culture. We further demonstrated that calycosin and gallic acid synergistically suppressed neutrophil infiltration and protected cardiac integrity in the isoproterenol-induced mice model of myocardial infarction. Calycosin and gallic acid dramatically suppressed isoproterenol-induced increase in myeloperoxidase (MPO) activity and malondialdehyde (MDA) level. Collectively, our results suggest that LTB4DH inducers (i.e., calycosin and gallic acid) may be a novel combined therapy for the treatment of neutrophil-mediated myocardial injury. PMID:26265982

  14. Anticipatory Nausea, Risk Factors, and Its Impact on Chemotherapy-Induced Nausea and Vomiting: Results From the Pan European Emesis Registry Study.

    Science.gov (United States)

    Molassiotis, Alexander; Lee, Paul H; Burke, Thomas A; Dicato, Mario; Gascon, Pere; Roila, Fausto; Aapro, Matti

    2016-06-01

    Anticipatory (prechemotherapy) nausea (AN) is a classic conditioned symptom not responding well to current antiemetics. Minimal work has been done to assess its risk factors and impact on chemotherapy-induced nausea and vomiting (CINV). To evaluate risk factors for AN and assess its impact on CINV development. We analyzed data (n = 991) from a prospective observational multisite study in eight European countries over three cycles of chemotherapy. Patient/treatment characteristics were collected before chemotherapy. History of nausea/vomiting (yes/no), patient expectation of CINV (0-100 mm visual analog scale, [VAS]), and prechemotherapy anxiety (0-100 mm VAS) also were collected before chemotherapy. A patient-completed diary during each chemotherapy cycle obtained information on AN in the 24 hours before chemotherapy administration and nausea and vomiting (episodes of vomiting and severity of nausea) daily for five days after administration of chemotherapy (0-100 mm VAS). AN was reported by 8.3%-13.8% of patients, increasing in frequency and intensity over each cycle. Every 1 mm increase in AN on the VAS was significantly associated with 2%-13% of increase in the likelihood of CINV (all P-values <0.05). Key predictors of AN in Cycle 1 included metastatic disease and prechemotherapy anxiety. However, predictors of AN in subsequent cycles included prechemotherapy anxiety and AN and CINV experience in the previous cycle, the latter being the strongest predictor (odds ratio = 3.30-4.09 for CINV outcomes over the cycles). AN is a challenging symptom, and its prevention needs to consider better CINV prevention in the previous cycles as well as managing prechemotherapy anxiety. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  15. Distinct cellular sources of hepoxilin A3 and leukotriene B4 are used to coordinate bacterial-induced neutrophil transepithelial migration.

    Science.gov (United States)

    Pazos, Michael A; Pirzai, Waheed; Yonker, Lael M; Morisseau, Christophe; Gronert, Karsten; Hurley, Bryan P

    2015-02-01

    Neutrophilic infiltration is a leading contributor to pathology in a number of pulmonary disease states, including cystic fibrosis. Hepoxilin A3 (HXA3) is a chemotactic eicosanoid shown to mediate the transepithelial passage of neutrophils in response to infection in several model systems and at multiple mucosal surfaces. Another well-known eicosanoid mediating general neutrophil chemotaxis is leukotriene B4 (LTB4). We sought to distinguish the roles of each eicosanoid in the context of infection of lung epithelial monolayers by Pseudomonas aeruginosa. Using human and mouse in vitro transwell model systems, we used a combination of biosynthetic inhibitors, receptor antagonists, as well as mutant sources of neutrophils to assess the contribution of each chemoattractant in driving neutrophil transepithelial migration. We found that following chemotaxis to epithelial-derived HXA3 signals, neutrophil-derived LTB4 is required to amplify the magnitude of neutrophil migration. LTB4 signaling is not required for migration to HXA3 signals, but LTB4 generation by migrated neutrophils plays a significant role in augmenting the initial HXA3-mediated migration. We conclude that HXA3 and LTB4 serve independent roles to collectively coordinate an effective neutrophilic transepithelial migratory response. Copyright © 2015 by The American Association of Immunologists, Inc.

  16. SNAP23-Dependent Surface Translocation of Leukotriene B4 (LTB4) Receptor 1 Is Essential for NOX2-Mediated Exocytotic Degranulation in Human Mast Cells Induced by Trichomonas vaginalis-Secreted LTB4.

    Science.gov (United States)

    Min, Arim; Lee, Young Ah; Kim, Kyeong Ah; El-Benna, Jamel; Shin, Myeong Heon

    2017-01-01

    Trichomonas vaginalis is a sexually transmitted parasite that causes vaginitis in women and itself secretes lipid mediator leukotriene B 4 (LTB 4 ). Mast cells are important effector cells of tissue inflammation during infection with parasites. Membrane-bridging SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complexes are critical for fusion during exocytosis. Although T. vaginalis-derived secretory products (TvSP) have been shown to induce exocytosis in mast cells, information regarding the signaling mechanisms between mast cell activation and TvSP is limited. In this study, we found that SNAP23-dependent surface trafficking of LTB 4 receptor 1 (BLT1) is required for nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2)-mediated exocytotic degranulation of mast cells induced by TvSP. First, stimulation with TvSP induced exocytotic degranulation and reactive oxygen species (ROS) generation in HMC-1 cells. Next, TvSP-induced ROS generation and exocytosis were strongly inhibited by transfection of BLT1 small interfering RNA (siRNA). TvSP induced trafficking of BLT1 from the cytosol to the plasma membrane. We also found that knockdown of SNAP23 abrogated TvSP-induced ROS generation, exocytosis, and surface trafficking of BLT1 in HMC-1 cells. By coimmunoprecipitation, there was a physical interaction between BLT1 and SNAP23 in TvSP-stimulated HMC-1 cells. Taken together, our results suggest that SNAP23-dependent surface trafficking of BLT1 is essential for exocytosis in human mast cells induced by T. vaginalis-secreted LTB 4 Our data collectively demonstrate a novel regulatory mechanism for SNAP23-dependent mast cell activation of T. vaginalis-secreted LTB 4 involving surface trafficking of BLT1. These results can help to explain how the cross talk mechanism between parasite and host can govern deliberately tissue inflammatory responses. Copyright © 2016 American Society for Microbiology.

  17. PHARMACOGENOMICS OF PROSTAGLANDIN AND LEUKOTRIENE RECEPTORS

    Directory of Open Access Journals (Sweden)

    José Antonio Cornejo-García

    2016-09-01

    Full Text Available Individual genetic background together with environmental effects are thought to be behind many human complex diseases. A number of genetic variants, mainly single nucleotide polymorphisms (SNPs, have been shown to be associated with various pathological and inflammatory conditions, representing potential therapeutic targets. Prostaglandins (PTGs and leukotrienes (LTs are eicosanoids derived from arachidonic acid and related polyunsaturated fatty acids that participate in both normal homeostasis and inflammatory conditions. These bioactive lipid mediators are synthesised through two major multistep enzymatic pathways: PTGs by cyclooxygenase and LTs by 5-lipoxygenase. The main physiological effects of PTGs include vasodilation and vascular leakage (PTGE2; mast cell maturation, eosinophil recruitment and allergic responses (PTGD2; vascular and respiratory smooth muscle contraction (PTGF2, and inhibition of platelet aggregation (PTGI2. LTB4 is mainly involved in neutrophil recruitment, vascular leakage, and epithelial barrier function, whereas cysteinyl LTs (CysLTs (LTC4, LTD4 and LTE4 induce bronchoconstriction and neutrophil extravasation, and also participate in vascular leakage. PTGs and LTs exert their biological functions by binding to cognate receptors, which belong to the seven transmembrane, G protein-coupled receptor superfamily. SNPs in genes encoding these receptors may influence their functionality and have a role in disease susceptibility and drug treatment response. In this review we summarize SNPs in PTGs and LTs receptors and their relevance in human diseases. We also provide information on gene expression. Finally, we speculate on future directions for this topic.

  18. Cysteinyl leukotrienes in the urine of patients with liver diseases.

    Science.gov (United States)

    Uemura, M; Buchholz, U; Kojima, H; Keppler, A; Hafkemeyer, P; Fukui, H; Tsujii, T; Keppler, D

    1994-10-01

    The significance of cysteinyl leukotrienes was investigated in patients with liver diseases by measurements of leukotriene E4 and N-acetyl-leukotriene E4 in urine. A marked increase of renal cysteinyl leukotriene excretion was observed in patients with cirrhosis without and with ascites, intrahepatic cholestasis, and obstructive jaundice as compared with healthy subjects (leukotriene E4: means 82, 264, 221 and 142 versus 40 nmol/mol creatinine, respectively; N-acetyl-leukotriene E4: means 25, 64, 61 and 47 versus 13 nmol/mol creatinine, respectively). The urinary concentration of leukotriene E4 was positively correlated with the one of N-acetyl-leukotriene E4 (r = 0.81, p jaundice, the excretion of leukotriene E4 plus N-acetyl-leukotriene E4 was positively correlated with total serum bilirubin. In patients with cirrhosis and in those with obstructive jaundice, the cysteinyl leukotrienes in urine were negatively correlated with creatinine clearance. The elevated renal excretion of cysteinyl leukotrienes decreased after biliary drainage in patients with obstructive jaundice. These data support the concept that increased urinary excretion of cysteinyl leukotrienes in patients with cirrhosis is due to a reduced functional liver mass and that in patients with cholestasis it is mainly due to an impaired elimination into the biliary tract that results in a diversion to renal excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Verification of the production of peptide leukotrienes (LT) in traumatic shock

    International Nuclear Information System (INIS)

    Hock, C.E.; Craft, D.V.; Lefer, D.J.; Lefer, A.M.

    1986-01-01

    Both lipoxygenase inhibition and leukotriene receptor antagonism have been demonstrated to provide significant protection in traumatic shock. Despite these findings, leukotrienes have not been found in circulating blood in Noble-Collip drum induced traumatic shock using radioimmunoassay techniques. Anesthetized rats subjected to Noble-Collip drum trauma developed a shock state characterized by a significant reduction in mean arterial blood pressure, a 4.5 fold increase in plasma cathepsin D activity, a 3-fold increase in myocardial depressant factor activity and a mean survival time of 1.9 +/- 0.3 hours. Plasma and bile samples were analyzed by reverse phase high pressure liquid chromatography to determine LT production in this shock model. No detectable peptide leukotrienes or their metabolites were found in plasma. The major peptide leukotriene from bile eluted between LTC 4 and LTD 4 and corresponds to a metabolite of LTE 4 , N-acetyl-LTE 4 . This metabolite increased from 6 +/- 3 to 41 +/- 4 units in traumatic shock when compared to sham trauma (p 4 , LTD 4 and LTE 4 (10 μg/kg/h) also resulted in the metabolism of > 90% of the parent LT to this metabolite in bile. Therefore, plasma LTs accumulate in the bile following trauma in rats. Moreover, LTC 4 , LTD 4 and LTE 4 apparently are rapidly metabolized to N-acetyl LTE 4 . These findings further support a role for leukotrienes in the pathogenesis of traumatic shock in rats

  20. Vascular effects of leukotriene D4 in human skin

    DEFF Research Database (Denmark)

    Bisgaard, H

    1987-01-01

    Leukotriene D4 (LTD4) increased the blood flow rate in human skin, equipotent to histamine in the dose range of 3.1-200 pmol. The vasodilatation lasted for up to 60 min, and no late reactions occurred. Indomethacin did not affect the LTD4-induced blood flow rate. H1 and H2 antagonists reduced...... as a mediator of the axon reflex, and show that LTD4 causes a direct vasodilatory effect that is not mediated via histamine or cyclooxygenase products. The laser-Doppler flowmeter was applied for dynamic studies of the vasopressor response in the skin during a Valsalva maneuver, and the relative changes...

  1. Susceptibility to endotoxin induced uveitis is not reduced in mice deficient in BLT1, the high affinity leukotriene B4 receptor

    OpenAIRE

    Smith, J R; Subbarao, K; Franc, D T; Haribabu, B; Rosenbaum, J T

    2004-01-01

    Aim: To investigate the role of arachidonic acid derived chemotactic factor, LTB4, in the development of endotoxin induced uveitis (EIU), using mice deficient in the BLT1 gene which encodes the high affinity LTB4 receptor.

  2. Pathophysiology of the cysteinyl leukotrienes and effects of leukotriene receptor antagonists in asthma

    DEFF Research Database (Denmark)

    Bisgaard, H

    2001-01-01

    , exudation of macromolecules and edema. The cysteinyl leukotrienes also have potent chemoattractant properties for eosinophils, causing an influx of eosinophils into the airway mucosa, which further fuels the inflammatory process. In addition, the cysteinyl leukotrienes are potent secretagogues and reduce...... and pranlukast inhibit bronchoconstriction in asthmatic patients undergoing allergen, exercise, cold air or aspirin challenge. They attenuate the hallmarks of asthmatic inflammation, including eosinophilia in the airway mucosa and peripheral blood. Moreover, exhaled nitric oxide concentrations, another correlate...

  3. 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.

    Science.gov (United States)

    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 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.

  4. The Role of Leukotriene B4 in Allergic Diseases

    Directory of Open Access Journals (Sweden)

    Hiroshi Ohnishi

    2008-01-01

    Full Text Available Leukotriene B4 (LTB4 is a lipid mediator with potent chemoattractant properties and that is rapidly generated from activated innate immune cells such as neutrophils, macrophages, and mast cells. Elevated levels of LTB4 have been reported in various allergic diseases and these levels have been related to disease activity and response to treatment. Recent studies using LTB4 receptor-1 (BLT1 antagonists or BLT1-deficient mice have revealed that ligation of BLT1 by LTB4 is important for the activation and recruitment of inflammatory cells including neutrophils, eosinophils, monocytes/macrophages, mast cells, dendritic cells, and more recently, effector T cells to inflamed tissues in various inflammatory diseases. The LTB4/BLT1 pathway appears to play an important role in the pathogenesis of severe persistent asthma, aspirin- and exercise-induced asthma, allergic rhinitis, and atopic dermatitis together with other mediators including cysteinyl leukotrienes, cytokines, and chemokines. LTB4 production is in general resistant to corticosteroid treatment. In fact, corticosteroids can upregulate BLT1 expression on corticosteroid-resistant inflammatory cells such as neutrophils, monocytes, and effector memory CD8+ T cells. As a result, this corticosteroid-resistant LTB4/BLT1 pathway may contribute to the development of inflammation in allergic diseases that do not respond to the introduction of corticosteroids. Inhibition of this pathway has potential therapeutic benefit in various allergic diseases that have involvement of corticosteroid-insensitivity.

  5. Factores que influyen en la emesis postaturdimiento en bovinos

    Directory of Open Access Journals (Sweden)

    Francisco Gerardo Ríos Rincón

    2012-01-01

    Full Text Available Para determinar el efecto del tiempo de espera pre-sacrificio, la efectividad del aturdimiento, el tipo de categoría comercial y la consistencia del contenido ruminal en la emesis durante el intervalo entre aturdimiento y desangrado en ganado bovino, se seleccionaron 9,446 canales en cuatro plantas procesadoras (P1, P2, P3, P4. El tiempo de espera pre-sacrificio se clasificó en: 1 menor a 3 h (T1; 2 de 3 a 12 h (T2; 3 mayor a 12 h (T3. El aturdimiento se registró como efectivo y no efectivo. La consistencia del contenido ruminal, se clasificó en: acuosa, semi-acuosa y espesa. En P1, se registró el número de cabezas y pulmones contaminados por emesis, y el análisis se realizó mediante X2. Cuando la espera pre-sacrificio fue mayor a 10 h y el aturdimiento no fue efectivo, el riesgo fue 1.73 veces mayor para observar contaminación de la canal. Al aumentar el tiempo de espera pre-sacrificio se incrementó (P<0.05 la emesis, cuando el contenido ruminal era acuoso (62.9 vs 12.5 y 24.6 %. La emesis fue similar (P=0.10; 10.07 % entre machos y hembras. El tiempo de espera pre-sacrificio y la categoría comercial del ganado no influyeron en la emesis post-aturdimiento. Se concluye que el efecto combinado de mayor tiempo de espera pre-sacrificio, aturdimiento no efectivo y consistencia acuosa del contenido ruminal, favorecen la emesis en bovinos durante el intervalo del aturdimiento al desangrado.

  6. Tratamiento psicológico de la emesis anticipatoria

    OpenAIRE

    Haro Martínez, Laura María

    2017-01-01

    La emesis por quimioterapia sigue siendo uno de los principales problemas que presentan los pacientes oncológicos y que puede afectar significativamente a su calidad de vida. La emesis anticipatoria es una respuesta aprendida a la quimioterapia que, según los estudios de Morrow, Roscoe, Kirshner, Hynes, y Rosenbluth en 1998, ocurre en un 25 % de los pacientes sobre el cuarto ciclo de tratamiento. Es una respuesta condicionada que aparece en pacientes que han desarrollado náuseas y vómitos imp...

  7. Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways

    Directory of Open Access Journals (Sweden)

    Cui Zhi-Hua

    2012-03-01

    Full Text Available Abstract Background Allergen induced early phase airway response and airway plasma exudation are predominantly mediated by inflammatory mast cell mediators including histamine, cysteinyl leukotrienes (cysLTs and thromboxane A2 (TXA2. The aim of the present study was to evaluate whether repeated allergen exposure affects early phase airway response to allergen challenge. Methods A trimellitic anhydride (TMA sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2 after allergen challenge. Results Repeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high-dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187 induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5-lipoxygenase and cyclooxygenase pathways. Conclusions The inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells.

  8. Recovery of brodifacoum in vomitus following induction of emesis in dogs that had ingested rodenticide bait.

    Science.gov (United States)

    Parton, K H; Willson, E K; Collett, M G; Booth, L H

    2018-01-01

    To assess the benefit of inducing emesis in dogs that have ingested rodenticide bait containing brodifacoum (BDF), by determining the amount of BDF in bait recovered from the vomitus relative to the estimated amount consumed. Between 2014 and 2015 samples of vomitus from seven dogs that ingested rodenticide baits containing BDF were submitted by veterinarians in New Zealand. All seven dogs had been given apomorphine by the veterinarian and vomited within 1 hour of ingesting the bait. Some or all of the bait particles were retrieved from each sample and were analysed for concentrations of BDF using HPLC. Based on estimations of the mass of bait consumed, the concentration of BDF stated on the product label, and the estimated mass of bait in the vomitus of each dog, the amount of BDF in the vomited bait was calculated as a percentage of the amount ingested. For five dogs an estimation of the mass of bait ingested was provided by the submitting veterinarian. For these dogs the estimated percentage of BDF in the bait retrieved from the vomitus was between 10-77%. All dogs were well after discharge but only one dog returned for further testing. This dog had a normal prothrombin time 3 days after ingestion. The induction of emesis within 1 hour of ingestion can be a useful tool in reducing the exposure of dogs to a toxic dose of BDF. The BDF was not fully absorbed within 1 hour of ingestion suggesting that the early induction of emesis can remove bait containing BDF before it can be fully absorbed.

  9. Significance of production of peptide leukotrienes in murine traumatic shock

    International Nuclear Information System (INIS)

    Craft, D.V.; Lefer, D.J.; Hock, C.E.; Lefer, A.M.

    1986-01-01

    The authors studied the formation of a leukotriene metabolite in plasma and bile during traumatic shock. Anesthetized rats subjected to Noble-Collip drum trauma developed a lethal shock state characterized by a survival time of 1.9 +/- 0.3h, a 4.5-fold increase in plasma cathepsin D activity, and a reduction in mean arterial blood pressure to 45 +/- 2 mmHg compared with 108 +/- 5 mmHg in sham-shock controls. Plasma and bile samples were analyzed by reverse-phase high-pressure liquid chromatography (HPLC) for peptide leukotrienes, and their retention times were confirmed by co-elution with radioactive standards, radioimmunoassay (RIA), and UV spectrophotometry. No leukotrienes or metabolites were found in plasma. The major peptide leukotriene from bile was eluted between LTC 4 and LTD 4 and corresponds to a metabolite of LTE 4 , N-acetyl-LTE 4 , which is also produced during endotoxin shock. The metabolite increased nearly sevenfold in traumatic shock compared with sham trauma. The identity of the metabolite was confirmed by UV scan, which revealed a spectrum consistent with a peptide leukotriene and similar to that of previously reported spectra for N-acetyl-LTE 4 . In conclusion, peptide leukotrienes are rapidly cleared from the blood and appear in the bile as N-acetyl-LTE 4 , a metabolite of the peptide leukotrienes. These findings support a role of the peptide leukotrienes in the pathogenesis of traumatic shock

  10. Mass spectrometry and metabolism of leukotriene B4

    International Nuclear Information System (INIS)

    Harper, T.W.

    1985-01-01

    Leukotriene B 4 (LTB 4 ) is a potent and powerful chemotactic factor for polymorphonuclear leukocytes and has been hypothesized to play a role as a mediator of the inflammatory response. A cell free system capable of generating leukotrienes from exogenous arachidonic acid was developed using both rat basophilic leukemia cells and murine mastocytoma cells. The cell free leukotriene generating system was used to prepare leukotrienes for mass spectral studies using electron impact (EI), chemical ionization (Cl), negative ion chemical ionization (NCl) and both positive and negative ion fast atom bombardment mass spectrometry (FAB-MS). Although all of the techniques examined yielded useful information, NCl was found to be the most useful for sensitive quantitation of leukotrienes, whereas Cl and El are more useful for unambiguous structural characterization of hydroxy fatty acid leukotrienes. Investigation of the in vivo metabolism of LTB 4 in the mouse and guinea pig indicated that less than 10% of the injected radiolabel from 3 H-LTB 4 was excreted via the urine and feces. Approximately 30% of the urinary radioactivity was volatile, probably due to loss of the tritium label as water. In the monkey, approximately 10% of the injected radiolabel from 14 C-LTB 4 was excreted in the urine within 5 1/2 hours. In this study, approximately 10% of the urinary radiolabel was volatile, with a large number of unidentified non-volatile products also observed. The isolated perfused rat lung was found to rapidly metabolize leukotriene C 4 to leukotrienes D 4 and E 4 and to leukotriene C 4 sulfoxide

  11. Factores que influyen en la emesis postaturdimiento en bovinos

    OpenAIRE

    Francisco Gerardo Ríos Rincón; Alfredo Estrada Angulo; Jorge Hernández Bautista; Cristina Pérez Linares; Jesús José Portillo Loera; Juan Carlos Robles Estrada

    2012-01-01

    Para determinar el efecto del tiempo de espera pre-sacrificio, la efectividad del aturdimiento, el tipo de categoría comercial y la consistencia del contenido ruminal en la emesis durante el intervalo entre aturdimiento y desangrado en ganado bovino, se seleccionaron 9,446 canales en cuatro plantas procesadoras (P1, P2, P3, P4). El tiempo de espera pre-sacrificio se clasificó en: 1) menor a 3 h (T1); 2) de 3 a 12 h (T2); 3) mayor a 12 h (T3). El aturdimiento se registró como efectivo y no efe...

  12. Emesis in monkeys following exposure to ionizing radiation

    International Nuclear Information System (INIS)

    Middleton, G.R.; Young, R.W.

    1975-01-01

    There were 129 male rhesus monkeys (Macaca mulatta) exposed to prompt radiations (neutron/gamma = 0.4 and pulse width = 50 ms) ranging from 700 to 5600 rad (midhead dose). The animals were fasted 18 h preexposure and observed for incidence of vomiting for 2 h postexposure. For doses less than 1000 rads, the number of animals that vomited increased directly with dose. Above 1000 rads, the number of animals that vomited decreased with increasing dose. The total number of vomits per dose group followed a nearly identical pattern to the incidence of emesis. In all dose groups, most of the emetic episodes occurred between 20 and 50 min postirradiation

  13. Evidence that 5-hydroxytryptamine3 receptors mediate cytotoxic drug and radiation-evoked emesis

    International Nuclear Information System (INIS)

    Miner, W.D.; Sanger, G.J.; Turner, D.H.

    1987-01-01

    The involvement of 5-hydroxytryptamine (5-HT) 5-HT 3 receptors in the mechanisms of severe emesis evoked by cytotoxic drugs or by total body irradiation have been studied in ferrets. Anti-emetic compounds tested were domperidone (a dopamine antagonist), metoclopramide (a gastric motility stimulant and dopamine antagonist at conventional doses, a 5-HT 3 receptor antagonist at higher doses) and BRL 24924 (a potent gastric motility stimulant and a 5-HT 3 receptor antagonist). Domperidone or metoclopramide prevented apomorphine-evoked emesis, whereas BRL 24924 did not. Similar doses of domperidone did not prevent emesis evoked by cis-platin or by total body irradiation, whereas metoclopramide or BRL 24924 greatly reduced or prevented these types of emesis. Metoclopramide and BRL 24924 also prevented emesis evoked by a combination of doxorubicin and cyclophosphamide. These results are discussed in terms of a fundamental role for 5-HT 3 receptors in the mechanisms mediating severely emetogenic cancer treatment therapies. (author)

  14. Endogenous leukotriene D4 formation during anaphylactic shock in the guinea pig

    International Nuclear Information System (INIS)

    Keppler, A.; Oerning, L.; Bernstroem, K.; Hammarstroem, S.

    1987-01-01

    Experiments on the metabolism and excretion of i.v. administered selectively labeled [ 3 H 8 ]leukotriene C 4 in bile duct-cannulated guinea pigs indicated predominantly biliary excretion of tritium. The major leukotriene metabolite in bile was identified as leukotriene D 4 . By monitoring leukotriene excretion radioimmunochromatographically, it was shown that guinea pigs suffering from anaphylactic shock produce leukotriene D 4 endogenously. Immunological challenge of animals sensitized to ovalbumin was accompanied by an increase of biliary leukotriene D 4 concentrations from 10 +/- 1 to 86 +/- 10 nM. When considering that bile flow was decreased to about half after challenge, the excretion rate of leukotriene D 4 in bile increased from 0.88 +/- 0.16 before 3.18 +/- 0.38 pmol x min -1 x kg -1 after challenge. It is concluded that systemic anaphylaxis in the guinea pig is associated with endogenous generation of leukotriene C 4

  15. Churg-Strauss syndrome and leukotriene antagonist use: a respiratory perspective.

    LENUS (Irish Health Repository)

    Nathani, N

    2008-10-01

    Churg-Strauss syndrome (CSS) is a rare granulomatous small vessel vasculitis that occurs against a background of longstanding asthma. Leukotriene antagonists (LTAs) are used in the management of asthma and may facilitate a reduction in steroid dosage. Reports of the development of CSS in patients with asthma following the initiation of LTA therapy suggest either a causal association or an unmasking of latent CSS as steroid doses fall. We have undertaken a systematic review to establish whether evidence of a drug induced syndrome exists.

  16. Upregulation of Leukotriene Receptors in Gastric Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Venerito, Marino [Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, Magdeburg 39120 (Germany); Kuester, Doerthe [Institute of Pathology, Otto-von-Guericke University, Leipziger Str. 44, Magdeburg 39120 (Germany); Harms, Caroline [Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, Magdeburg 39120 (Germany); Schubert, Daniel [Department of General, Visceral and Vascular Surgery, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, Magdeburg 39120 (Germany); Wex, Thomas, E-mail: thomas.wex@med.ovgu.de; Malfertheiner, Peter [Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, Magdeburg 39120 (Germany)

    2011-08-08

    Leukotrienes (LT) mediate allergic and inflammatory processes. Previously, we identified significant changes in the expression pattern of LT receptors in the gastric mucosa after eradication of Helicobacter pylori infection. The aim of the present study was to evaluate the expression of 5-lipoxygenase (5-LOX) and LT receptors in gastric cancer (GC). The expression of 5-LOX and receptors for LTB4 (BLT-1, BLT-2) and cysteinyl-LT (CysLT-1, CysLT-2) were analyzed by immunohistochemistry (IHC) in GC samples of 35 consecutive patients who underwent gastrectomy and in 29 tumor-free tissue specimens from gastric mucosa. Male-to-female ratio was 24:11. The median age was 70 years (range 34–91). Twenty-two patients had GC of intestinal, six of diffuse, six of mixed and one of undifferentiated type. The IHC analysis showed a nearly ubiquitous expression of studied proteins in GC (88–97%) and in tumor-free specimens as well (89–100%). An increase in the immunoreactive score of both BLT receptors and CysLT-1 was observed in GC compared to tumor-free gastric mucosa (p < 0.001 for BLT-1; p < 0.01 for BLT-2 and CysLT-1, Mann-Whitney U-test). No differences in the IHC expression of 5-LOX and CsyLT-2 were observed between GC and tumor-free mucosa. The expression of BLT-2, CysLT-1 and CysLT-2 was increased in GC of intestinal type when compared to the diffuse type (p < 0.05; Mann-Whitney U-test). LTB4 receptors and CysLT-1 are up-regulated in GC tissue implying a role in gastric carcinogenesis.

  17. Cysteinyl-Leukotriene Receptors and Cellular Signals

    Directory of Open Access Journals (Sweden)

    G. Enrico Rovati

    2007-01-01

    Full Text Available Cysteinyl-leukotrienes (cysteinyl-LTs exert a range of proinflammatory effects, such as constriction of airways and vascular smooth muscle, increase of endothelial cell permeability leading to plasma exudation and edema, and enhanced mucus secretion. They have proved to be important mediators in asthma, allergic rhinitis, and other inflammatory conditions, including cardiovascular diseases, cancer, atopic dermatitis, and urticaria. The classification into subtypes of the cysteinyl-LT receptors (CysLTRs was based initially on binding and functional data, obtained using the natural agonists and a wide range of antagonists. CysLTRs have proved remarkably resistant to cloning. However, in 1999 and 2000, the CysLT1R and CysLT2R were successfully cloned and both shown to be members of the G-protein coupled receptors (GPCRs superfamily. Molecular cloning has confirmed most of the previous pharmacological characterization and identified distinct expression patterns only partially overlapping. Recombinant CysLTRs couple to the Gq/11 pathway that modulates inositol phospholipids hydrolysis and calcium mobilization, whereas in native systems, they often activate a pertussis toxin-insensitive Gi/o-protein, or are coupled promiscuously to both G-proteins. Interestingly, recent data provide evidence for the existence of an additional receptor subtype that seems to respond to both cysteinyl-LTs and uracil nucleosides, and of an intracellular pool of CysLTRs that may have roles different from those of plasma membrane receptors. Finally, a cross-talk between the cysteinyl-LT and the purine systems is being delineated. This review will summarize recent data derived from studies on the molecular and cellular pharmacology of CysLTRs.

  18. Influence of leukotriene gene polymorphisms on chronic rhinosinusitis

    Directory of Open Access Journals (Sweden)

    Duval Melanie

    2008-03-01

    Full Text Available Abstract Background Chronic rhinosinusitis (CRS is increasingly viewed as an inflammatory condition of the sinonasal mucosa interacting with bacteria and/or fungi. However, factors conferring susceptibility to disease remain unknown. Advances in genomics offer powerful tools to explore this disorder. The goal of this study was to evaluate the effect of single nucleotide polymorphisms (SNP on CRS in a panel of genes related to cysteinyl leukotriene metabolism. Methods Severe cases of CRS and postal code match controls were recruited prospectively. A total of 206 cases and 200 controls were available for the present study. Using a candidate gene approach, five genes related to cysteinyl leukotriene metabolism were assessed. For each gene, we selected the maximally informative set of common SNPs (tagSNPs using the European-derived (CEU HapMap dataset. These SNPs are in arachidonate 5-lipoxygenase (ALOX5, arachidonate 5-lipoxygenase-activating protein (ALOX5AP, leukotriene C4 synthase (LTC4S, cysteinyl leukotriene receptor 1 (CYSLTR1 and cysteinyl leukotriene receptor 2 (CYSLTR2 genes. Results A total of 59 SNPs were genotyped to capture the common genetic variations within these genes. Three SNPs located within the ALOX5, CYSLTR1 and ALOX5AP genes reached the nominal p-value threshold (p Conclusion While these initial results do not support that polymorphsims in genes assessed involved in the leukotriene pathways are contributing to the pathogenesis of CRS, this initial study was not powered to detect polymorphisms with relative risk of 2.0 or less, where we could expect many gene effects for complex diseases to occur. Thus, despite this lack of significant association noted in this study, we believe that validation with external populations and the use of better-powered studies in the future may allow more conclusive findings.

  19. Effects of cysteinyl leukotrienes and leukotriene receptor antagonists on markers of inflammation

    DEFF Research Database (Denmark)

    Sampson, Anthony P; Pizzichini, Emilio; Bisgaard, Hans

    2003-01-01

    mediators in a wide range of diseases, implying that their biological activities reach far beyond acute bronchoconstriction, the activity traditionally ascribed to them. The validity of examining sputum for "biomarkers" has improved the understanding of asthma pathophysiology, optimization of asthma......The understanding that asthma pathophysiology includes an inflammatory component has spurred the more aggressive use of anti-inflammatory therapies and created a need for effective tools to measure inflammation. Biomarkers of airway inflammation proposed are obtained by methods that are direct...... but highly invasive (bronchial biopsy, bronchoalveolar lavage), moderately direct, and less invasive (indirect sputum, exhaled air, breath condensate) or indirect and least invasive (blood, urine). Several studies described in this review have implicated the cysteinyl leukotrienes (CysLTs) as inflammatory...

  20. [Leukotriene antagonists: a new approach in the treatment of asthma].

    Science.gov (United States)

    Devillier, P; Bessard, G; Advenier, C

    1997-06-01

    Inflammation plays an essential role in the genesis of airflow obstruction and bronchial hyper-reactivity in the early stages of clinical asthma. The treatment of bronchial inflammation has become an essential element in the therapeutic strategy and principally rests on inhaled glucocorticoids. Amongst a number of inflammatory mediators leukotrienes occupy a privileged place by the power of their inflammatory and constrictor effects on bronchial smooth muscles. These properties have justified the clinical development of inhibitors of their synthesis and of specific antagonists to their receptors. Leukotriene antagonists are specific for a sub type of leukotriene receptors C4, D4 and E4 which is implicated in the majority of the bronchial constrictor and inflammatory effects of leukotrienes. The antagonists of Cys-LT1 receptor but also the inhibitors of the leukotriene synthesis exert an additive bronchodilator effect to those of B2 stimulants confirming an efficacious protection vis a vis bronchial provocation tests and above all they improve the clinical scores, lung function and also enable a decrease in the consumption of beta 2 agonists. The marketing of these products represents a major event because it corresponds to the advent of a new therapeutic class. The ease of administration by the oral route, their demonstrated efficacy and their good tolerance profile (in particular for ICI 204.219, and antagonists to Cys-LT1 receptors) are elements which foresee a success for this new asthmatic treatment. However numerous studies, notably comparative studies vis a vis reference treatments will be necessary to define their place in the strategic approach to the treatment of asthma.

  1. A Multinational Study to Measure the Value that Patients with Cancer Place on Improved Emesis Control Following Cisplatin Chemotherapy

    OpenAIRE

    George Dranitsaris; Pauline Leung; Renoto Ciotti; Ana Ortega; Maria Spinthouri; Lycurgus Liaropoulos; Roberto Labianca; Antonello Quadri

    2001-01-01

    Background: The neurokinin-1 (NK1) receptor antagonists are a new class of agents designed to reduce the risk of emesis following chemotherapy, particularly with cisplatin. Early data from double-blind randomised trials suggest that an orally administered NK1 antagonist can reduce the absolute risk of acute and delayed emesis following cisplatin by 20 and 30%, respectively. Objective: To measure the value that patients with cancer place on improved emesis control and quality of life. Design: ...

  2. Granistron and dexamethasone provide more improved prevention of postoperative emesis than granisetron alone in children.

    Science.gov (United States)

    Fujii, Y; Tanaka, H; Toyooka, H

    1996-12-01

    Dexamethasone decreases chemotherapy-induced emesis when added to antiemetic regimens. This study was designed to compare the effectiveness of granisetron and dexamethasone with granisetron alone in the prevention of post-operative vomiting after strabismus repair, tonsillectomy with or without adenoidectomy in children. In a randomized, double-blind study, 60 healthy children, 4-10 yr of age, received either granisetron 40 micrograms.kg-1 and saline (Group S) or granisetron 40 micrograms.kg-1 and dexamethasone 4 mg (Group D) iv immediately after the induction of anaesthesia. All subjects received anaesthetics consisting of sevoflurane and nitrous oxide in oxygen Postoperative pain was treated with acetaminophen pr or pentazocine iv. Postoperatively, during the first 24 hr after anaesthesia, the frequencies of retching and vomiting, and the incidence of adverse events were recorded by nursing staff. There were no differences between the treatment groups with regard to demographics, surgical procedure, anaesthetic administered or analgesics used for postoperative pain. The frequency of the symptoms was 27% and 7% in Groups S and D, respectively (P < 0.05). The incidence of adverse events was comparable in the two groups. The prophylactic administration of granisetron and dexamethasone was more effective than granisetron alone in the prevention of postoperative vomiting in paediatric subjects undergoing strabismus repair, tonsillectomy and adenoidectomy.

  3. Evidence that 5-hydroxytryptamine/sub 3/ receptors mediate cytotoxic drug and radiation-evoked emesis

    Energy Technology Data Exchange (ETDEWEB)

    Miner, W.D.; Sanger, G.J.; Turner, D.H.

    1987-08-01

    The involvement of 5-hydroxytryptamine (5-HT) 5-HT/sub 3/ receptors in the mechanisms of severe emesis evoked by cytotoxic drugs or by total body irradiation have been studied in ferrets. Anti-emetic compounds tested were domperidone (a dopamine antagonist), metoclopramide (a gastric motility stimulant and dopamine antagonist at conventional doses, a 5-HT/sub 3/ receptor antagonist at higher doses) and BRL 24924 (a potent gastric motility stimulant and a 5-HT/sub 3/ receptor antagonist). Domperidone or metoclopramide prevented apomorphine-evoked emesis, whereas BRL 24924 did not. Similar doses of domperidone did not prevent emesis evoked by cis-platin or by total body irradiation, whereas metoclopramide or BRL 24924 greatly reduced or prevented these types of emesis. Metoclopramide and BRL 24924 also prevented emesis evoked by a combination of doxorubicin and cyclophosphamide. These results are discussed in terms of a fundamental role for 5-HT/sub 3/ receptors in the mechanisms mediating severely emetogenic cancer treatment therapies.

  4. Bronchial effects of leukotriene D4 inhalation in normal human lung

    DEFF Research Database (Denmark)

    Bisgaard, H; Groth, S

    1987-01-01

    airways in asthmatic patients out of attack. LTD4 caused a dose-dependent obstruction of the airways as measured by partial flow-volume curves and volume of trapped gas, yet only minor changes in forced expiratory volume in 1 s (FEV1) and peak expiratory flow rate. LTD4 was 1900-7000 times more potent......The aim of the study was to investigate whether inhaled leukotriene (LT) D4 could mimic the characteristics of asthmatic patients after allergen-induced attack, i.e. a prolonged subclinical bronchial obstruction, an increased reactivity of the airways and a late reaction. The effects of LTD4 were...... than histamine. LTD4 inhalations were almost symptomless as opposed to the irritative and dyspnoeic symptoms seen after inhalation of histamine. The time duration for the induced change in partial flow-volume curves was the same for the two drugs. Approximately 30 min elapsed until the bronchial...

  5. Pharmacological modulation of human platelet leukotriene C4-synthase.

    Science.gov (United States)

    Sala, A; Folco, G; Henson, P M; Murphy, R C

    1997-03-21

    The aim of this study was to test if human platelet leukotriene C4-synthase (LTC4-S) is pharmacologically different from cloned and expressed LTC4-S and, in light of the significant homologies between 5-lipoxygenase activating protein (FLAP) and LTC4-S, if different potencies of leukotriene synthesis inhibitors acting through binding with FLAP (FLAP inhibitors) reflect in different potencies as LTC4-S inhibitors. Leukotriene C4 (LTC4) synthesis by washed human platelets supplemented with synthetic leukotriene A4 (LTA4) was studied in the absence and presence of two different, structurally unrelated FLAP inhibitors (MK-886 and BAY-X1005) as well as a direct 5-lipoxygenase inhibitor (zileuton). LTC4 production was analyzed by RP-HPLC coupled to diode array detection. We report that human platelet LTC4-S was inhibited by MK-886 and BAY-X1005 (IC50 of 4.7 microM and 91.2 microM, respectively), but not by zileuton (inactive up to 300 microM); all 3 compounds were able to inhibit 5-lipoxygenase metabolite biosynthesis in intact human polymorphonuclear leukocytes (IC50 of 0.044 microM, 0.85 microM, and 1.5 microM, respectively). Platelet LTC4-S does not appear pharmacologically different from expression cloned LTC4-S. LTC4-S inhibition by FLAP inhibitors is in agreement with the significant homology reported for expression-cloned LTC4-S with FLAP, Furthermore, functional homology of the binding sites for inhibitors on LTC4-S and FLAP is suggested by the conservation of the relative potencies of MK-886 and BAY-X1005 vs FLAP-dependent 5-lipoxygenase activity and LTC4-S inhibition: MK-886 was 19.3-fold more potent than BAY-X1005 as FLAP inhibitor and 19.6-fold more potent than BAY-X1005 as LTC4-S inhibitor.

  6. Role of leukotrienes in asthma pathophysiology

    DEFF Research Database (Denmark)

    Bisgaard, H

    2000-01-01

    -line anti-inflammatory therapy for asthma management. However, in some patients, especially children, the high doses of corticosteroids that may be required to control features of hyperresponsiveness, including exercise-induced asthma, raise safety concerns. Thus, there is a need for complementary anti...

  7. A radiochemical assay for detection of leukotriene B4 production from isolated cells

    International Nuclear Information System (INIS)

    Aharony, D.; Dobson, P.; Krell, R.D.

    1984-01-01

    A radiochemical procedure for quantitating the effect of inhibitors of leukotriene B4 (LTB4) biosynthesis is described. Rat peritoneal cells were labeled with 3 H-arachidonic acid and stimulated with the calcium ionophore A23187. 3 H-LTB4 was isolated by processing on C18-Sep Pak cartridges followed by reverse-phase high pressure liquid chromatography (HPLC). The identity of this product, as well as other arachidonic acid metabolites, was verified by using silicic acid column chromatography followed by straight-phase HPLC and thin layer chromatography. Using this assay, LTB4 release by ionophore A23187 has been shown to be both time- and concentration-dependent. Indomethacin enhanced, while NDGA and ETYA inhibited, the A23187-induced production of LTB4. This procedure is both simple and direct and is capable of assessing the ability of novel compounds to alter LTB4 production

  8. The anti-asthmatic drug pranlukast suppresses the delayed-phase vomiting and reverses intracellular indices of emesis evoked by cisplatin in the least shrew (Cryptotis parva).

    Science.gov (United States)

    Darmani, Nissar A; Chebolu, Seetha; Zhong, Weixia; Kim, William D; Narlesky, Matthew; Adams, Joia; Dong, Fanglong

    2017-08-15

    The introduction of second generation serotonin 5-HT 3 receptor (5-HT 3 ) antagonist palonosetron combined with long-acting substance P neurokinin NK 1 receptor (NK 1 ) antagonists (e.g. netupitant) has substantially improved antiemetic therapy against early- and delayed-phases of emesis caused by highly emetogenic chemotherapeutics such as cisplatin. However, the improved efficacy comes at a cost that many patients cannot afford. We introduce a new class of antiemetic, the antiasthmatic leukotriene CysLT1 receptor antagonist pranlukast for the suppression of cisplatin-evoked vomiting. Pranlukast (10mg/kg) by itself significantly reduced the mean frequency of vomits (70%) and fully protected least shrews from vomiting (46%) during the delayed-phase of cisplatin (10mg/kg)-evoked vomiting. Although, pranlukast tended to substantially reduce both the mean frequency of vomits and the number of shrews vomiting during the early-phase, these reductions failed to attain significance. When combined with a first (tropisetron)- or a second (palonosetron)-generation 5-HT 3 receptor antagonist, pranlukast potentiated their antiemetic efficacy during both phases of vomiting. In addition, pranlukast by itself prevented several intracellular signal markers of cisplatin-evoked delayed-vomiting such as phosphorylation of ERK1/2 and PKA. When pranlukast was combined with either palonosetron or tropisetron, these combinations suppressed the evoked phosphorylation of: i) ERK1/2 during both acute- and delayed-phase, ii) PKCα/β at the peak acute-phase, and iii) PKA at the peak delayed-phase. The current and our published findings suggest that overall behavioral and intracellular signaling effects of pranlukast via blockade of CysLT1 receptors generally appear to be similar to the NK 1 receptor antagonist netupitant with some differences. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Emesis as a Screening Diagnostic for Low Dose Rate (LDR) Total Body Radiation Exposure.

    Science.gov (United States)

    Camarata, Andrew S; Switchenko, Jeffrey M; Demidenko, Eugene; Flood, Ann B; Swartz, Harold M; Ali, Arif N

    2016-04-01

    Current radiation disaster manuals list the time-to-emesis (TE) as the key triage indicator of radiation dose. The data used to support TE recommendations were derived primarily from nearly instantaneous, high dose-rate exposures as part of variable condition accident databases. To date, there has not been a systematic differentiation between triage dose estimates associated with high and low dose rate (LDR) exposures, even though it is likely that after a nuclear detonation or radiologic disaster, many surviving casualties would have received a significant portion of their total exposure from fallout (LDR exposure) rather than from the initial nuclear detonation or criticality event (high dose rate exposure). This commentary discusses the issues surrounding the use of emesis as a screening diagnostic for radiation dose after LDR exposure. As part of this discussion, previously published clinical data on emesis after LDR total body irradiation (TBI) is statistically re-analyzed as an illustration of the complexity of the issue and confounding factors. This previously published data includes 107 patients who underwent TBI up to 10.5 Gy in a single fraction delivered over several hours at 0.02 to 0.04 Gy min. Estimates based on these data for the sensitivity of emesis as a screening diagnostic for the low dose rate radiation exposure range from 57.1% to 76.6%, and the estimates for specificity range from 87.5% to 99.4%. Though the original data contain multiple confounding factors, the evidence regarding sensitivity suggests that emesis appears to be quite poor as a medical screening diagnostic for LDR exposures.

  10. Cold injury, blood-brain barrier changes, and leukotriene synthesis: Inhibition by phenidone

    International Nuclear Information System (INIS)

    Robichaud, L.J.; Marcoux, F.W.

    1990-01-01

    Transcranial cold injury in rats and guinea pigs induced cerebral extravasation of albumin labeled with Evans blue dye or 125 I, respective indicators of the area and amount of blood-brain barrier (BBB) disruption. Radioimmunoassay of brain extracts showed that cold injury induced leukotriene (LT)C4 in rat and guinea pig brains 15 min after injury. In guinea pigs, the LT synthesis inhibitor phenidone (30 mg/kg, i.p.) completely blocked cold-induced LTC4 in brain. Phenidone (30 and 100 mg/kg) also inhibited cerebral tissue accumulation of 125 I-albumin and dye in rats and guinea pigs. Phenidone is reported to show antioxidant properties and selective lipoxygenase inhibition of arachidonic acid metabolism compared to cyclooxygenase inhibitors, meclofenamate sodium, and other nonsteroidal anti-inflammatory agents. Since several oxygen and hydroxyl radical scavengers and the cyclooxygenase inhibitor, meclofenamate sodium, did not inhibit protein extravasation, the findings support a role for LT as a mediator of cold-induced changes in BBB permeability in rats and guinea pigs and suggest that the inhibitory effects of phenidone on BBB permeability may be due to inhibition of LT production

  11. COMPARISON OF SELECTIVE AND NON SELECTIVE CYCLO-OXYGENASE 2 INHIBITORS IN EXPERIMENTAL COLITIS EXACERBATION: role of leukotriene B4 and superoxide dismutase

    Directory of Open Access Journals (Sweden)

    José Wander BREGANÓ

    2014-09-01

    Full Text Available Context Nonsteroidal anti-inflammatory drugs are considered one of the most important causes of reactivation of inflammatory bowel disease. With regard to selective cyclo-oxygenase 2 inhibitors, the results are controversial in experimental colitis as well as in human studies. Objectives The aim this study is to compare nonsteroidal anti-inflammatory drugs effects, selective and non selective cyclo-oxygenase 2 inhibitors, in experimental colitis and contribute to the understanding of the mechanisms which nonsteroidal anti-inflammatory drugs provoke colitis exacerbation. Methods Six groups of rats: without colitis, with colitis, and colitis treated with celecoxib, ketoprofen, indometacin or diclofenac. Survival rates, hemoglobin, plasmatic albumin, colonic tissue of interleukin-1ß, interleukin-6, tumor necrosis factor alpha, prostaglandin E2, catalase, superoxide dismutase, thiobarbituric acid-reactive substances, chemiluminescence induced by tert-butil hydroperoxides, and tissue and plasmatic leukotriene B4 were determined. Results The groups treated with diclofenac or indometacin presented lower survival rates, hemoglobin and albumin, higher tissue and plasmatic leukotriene B4 and tissue superoxide dismutase than the group treated with celecoxib. Ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib, concerning to survival rate and albumin. The groups without colitis, with colitis and with colitis treated with celecoxib showed leukotriene B4 and superoxide dismutase lower levels than the groups treated with nonselective cyclo-oxygenase 2 inhibitors. Conclusions Diclofenac and indometacin presented the highest degree of induced colitis exacerbation with nonsteroidal anti-inflammatory drugs, celecoxib did not show colitis exacerbation, and ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib. These results suggest that leukotriene B4 and superoxide dismutase can be

  12. Clinical predictors of anticipatory emesis in patients treated with chemotherapy at a tertiary care cancer hospital

    OpenAIRE

    Qureshi, Fawad; Shafi, Azhar; Ali, Sheeraz; Siddiqui, Neelam

    2016-01-01

    Objective: To determine the clinical predictors of anticipatory emesis in patients treated with chemotherapy at a tertiary care cancer hospital. Methods: This was a cross-sectional study conducted on 200 patients undergoing first line chemotherapy with minimum of two cycles at inpatient department and chemotherapy bay of Shaukat Khanum Memorial Cancer Hospital and Research Centre Pakistan. Anticipatory nausea and vomiting develops before administration of chemotherapy. Clinical signs and symp...

  13. Effect of postoperative dexamethasone on pain, emesis and haemorrhage in tonsillectomy by dissection method

    International Nuclear Information System (INIS)

    Khan, K.A.; Faiz, S.B.

    2013-01-01

    Objectives: To compare the effect of postoperative intravenous dose of dexamethasone on morbidity in patients undergoing tonsillectomy. Design: Randomized control trial. Place and Duration of Study: This study was conducted in ENT Department Shaikh Khalifa Bin Zayed Al Nahyan Hospital (CMH) Muzaffarabad from 10th Jan 2010 to 15th Feb 2011. Patients and Methods: After getting informed consent, a total of 60 patients who fulfilled the inclusion criteria were selected and tonsillectomy by dissection method was carried out. They were divided into two groups of 30 each using a random numbers table. Group A received 0.25 mg/kg body weight (maximum 20 mg) of Dexamethasone postoperatively intravenously for 03 days while group B (control group) did not receive any steroid. Results: In group A, 80% patients had mild pain, 16.7% had moderate pain and 3.3% had a severe pain while in group B, 30% patients had mild pain, 6.7% had moderate pain and 63.3% had severe pain (p< 0.05). In group A, 76.7% patients had mild emesis while in group B, 86.7% had moderate emesis (p< 0.05). There was an insignificant difference in secondary hemorrhage. Conclusion: Dexamethasone given postoperatively significantly reduces the morbidity that is pain, episodes of emesis thus early recovery to a normal lifestyle with no effect on secondary hemorrhage in patients undergoing Tonsillectomy by dissection method. (author)

  14. Elevated Plasma Level of Leukotrienes in Bronchial Asthma Patients: A Possible Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Mahmoud Mansour

    1994-01-01

    Full Text Available Plasma from bronchial asthma patients and healthy controls was investigated for the content of lipoxygenase products. After lipid extraction using SEP-PAK C18 Cartridges, the lipoxygenase products were measured by Enzyme-Immunoassay. Elevated chemotactic B4 was found in plasma from asthmatic patients with mean value (483±75 pmoUL, while the mean value in normal healthy donors was (140± 12.1 pmol/L (M±SE. The levels of spasmogenic cysteinyl containing leukotrienes were also very high in the bronchial asthma patients. Elevations of leukotriene B4 and cysteinyl containing leukotrienes were detected during attacks of bronchial asthma. These results suggest that leukotriene B4 may be important in the pathogenesis of bronchial asthma and confirmed that peptidoleukotrienes playa role as chemical mediators during the asthmatic attack.

  15. Carbon monoxide inhibits omega-oxidation of leukotriene B4 by human polymorphonuclear leukocytes: evidence that catabolism of leukotriene B4 is mediated by a cytochrome P-450 enzyme.

    Science.gov (United States)

    Shak, S; Goldstein, I M

    1984-09-17

    Carbon monoxide significantly inhibits omega-oxidation of exogenous leukotriene B4 to 20-OH-leukotriene B4 and 20-COOH-leukotriene B4 by unstimulated polymorphonuclear leukocytes as well as omega-oxidation of leukotriene B4 that is generated when cells are stimulated with the calcium ionophore, A23187. Inhibition of omega-oxidation by carbon monoxide is concentration-dependent, completely reversible, and specific. Carbon monoxide does not affect synthesis of leukotriene B4 by stimulated polymorphonuclear leukocytes or other cell functions (i.e., degranulation, superoxide anion generation). These findings suggest that a cytochrome P-450 enzyme in human polymorphonuclear leukocytes is responsible for catabolizing leukotriene B4 by omega-oxidation.

  16. A multinational study to measure the value that patients with cancer place on improved emesis control following cisplatin chemotherapy.

    Science.gov (United States)

    Dranitsaris, G; Leung, P; Ciotti, R; Ortega, A; Spinthouri, M; Liaropoulos, L; Labianca, R; Quadri, A

    2001-01-01

    The neurokinin-1 (NK1) receptor antagonists are a new class of agents designed to reduce the risk of emesis following chemotherapy, particularly with cisplatin. Early data from double-blind randomised trials suggest that an orally administered NK1 antagonist can reduce the absolute risk of acute and delayed emesis following cisplatin by 20 and 30%, respectively. To measure the value that patients with cancer place on improved emesis control and quality of life. Willingness-to-pay analysis. Five study sites in Canada, Italy, Spain and Greece. 245 patients with cancer either receiving chemotherapy with cisplatin or who had received cisplatin-based chemotherapy within the previous 6 months. After background information had been presented, patients were asked to define the maximum that they would pay per day for a drug that reduced their risk of acute and delayed (days 2 to 5) emesis by 20 and 30%, respectively. Costs were converted to US dollars ($US) using year 2000 exchange rates. For a 20% improvement in acute emesis, Canadian, Italian and Spanish patients with cancer were willing to pay $US46, $US34 and $US63 per day, respectively, compared with $US8 for patients from Greece (p < 0.001). For a 30% improvement in delayed emesis, Canadian, Italian and Spanish patients with cancer were also willing to pay more than their Greek counterparts (SUS41, $US31, $US50 and $US9 daily for 4 days, respectively; p < 0.001). These significant differences in patient value between countries remained, even after adjusting for socioeconomic variables and previous history of emesis. There are substantial cultural differences in how patients with cancer value benefit and improved quality of life. Since the majority of the world's population resides outside North America and Western Europe, there may be a need to re-evaluate perceived levels of patient benefit and measures of quality of life.

  17. Leukotriene C4 synthase and ischemic cardiovascular disease and obstructive pulmonary disease in 13,000 individuals

    DEFF Research Database (Denmark)

    Freiberg, Jacob J; Dahl, Morten; Tybjaerg-Hansen, Anne

    2009-01-01

    Ischemic cardiovascular disease and obstructive pulmonary disease involve inflammation. Leukotrienes may be important pro-inflammatory mediators. We tested the hypothesis that the (-1072)G > A and (-444)A > C promoter polymorphisms of leukotriene C4 synthase confer risk of transient ischemic atta...... with risk of asthma or COPD. Leukotriene C4 synthase promoter genotypes influence risk of TIA and ischemic stroke, but not risk of IHD/coronary atherosclerosis, asthma, or COPD....

  18. Hepatic Warm Ischemia-Reperfusion-Induced Increase in Pulmonary Capillary Filtration Is Ameliorated by Administration of a Multidrug Resistance-Associated Protein 1 Inhibitor and Leukotriene D4 Antagonist (MK-571) Through Reducing Neutrophil Infiltration and Pulmonary Inflammation and Oxidative Stress in Rats.

    Science.gov (United States)

    Yeh, D Y-W; Yang, Y-C; Wang, J-J

    2015-05-01

    Hepatopulmonary syndrome (HPS) is the major complication subsequent to liver ischemia and reperfusion (I/R) injury after resection or transplantation of liver. Hallmarks of HPS include increases in pulmonary leukotrienes and neutrophil recruitment and infiltrating across capillaries. We aimed to investigate the protective efficacy of MK-571, a multidrug resistance-associated protein 1 inhibitor and leukotriene D4 agonist, against hepatic I/R injury-associated change in capillary filtration. Eighteen Sprague-Dawley male rats were evenly divided into a sham-operated group, a hepatic I/R group, and an MK-571-treated I/R group. MK-571 was administered intraperitoneally 15 min before hepatic ischemia and every 12 hours during reperfusion. Ischemia was conducted by occluding the hepatic artery and portal vein for 30 min, followed by removing the clamps and closing the incision. Forty-eight hours after hepatic ischemia, we assessed the pulmonary capillary filtration coefficient (Kfc) through the use of in vitro-isolated, perfused rat lung preparation. We also measured the lung wet-to-dry weight ratio (W/D) and protein concentration in broncho-alveolar lavage fluid (PCBAL). Lung inflammation and oxidative stress were evaluated by use of tissue tumor necrosis factor (TNF)-α and malondialdehyde levels and lavage differential macrophage and neutrophil cell count. Hepatic I/R injury markedly increased Kfc, W/D, PCBAL, tissue TNF-α level, and differential neutrophil cell count (P < .05). MK-571 treatment reduced neutrophil infiltration and lung inflammation and improved pulmonary capillary filtration, collectively suggesting lung protection. Treatment with MK-571 before and during hepatic ischemia and reperfusion protects lung against pulmonary capillary barrier function impairment through decreasing pulmonary lung inflammation and lavage neutrophils. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Effects of menadione, a reactive oxygen generator, on leukotriene secretion from RBL-2H3 cells.

    Science.gov (United States)

    Kawamura, Fumio; Nakanishi, Mamoru; Hirashima, Naohide

    2010-01-01

    Reactive oxygen species (ROS) are produced in various cells and affect many biological processes. We previously reported that 2-methyl-1,4-naphtoquinone (menadione) inhibited Ca(2+) influx from the extracellular medium and exocytosis evoked by antigen stimulation in the mast cell line, RBL-2H3. Mast cells release various inflammatory mediators such as leukotrienes (LTs) and cytokines in addition to the exocytotic secretion of histamine. In this study, we investigated the effects of menadione on LT release in RBL-2H3. Treatment of RBL cells with menadione inhibited LTC(4) secretion induced by antigen stimulation. To elucidate the mechanism of this inhibition, we examined the effects of menadione on the activation process of 5-lipoxygenase that is responsible for the synthesis of LTs from arachidonic acid. Menadione did not affect the phosophorylation of mitogen activated protein (MAP) kinases, extracellular signal-regulated kinase (ERK) and p38, which regulates phosphorylation of 5-lipoxygenase. However, menadione inhibited the translocation of 5-lipoxygenase from the cytoplasm to the nuclear membrane. Together with the result that LT secretion was severely impaired in the absence of extracellular Ca2(2+), it is suggested that ROS produced by menadione inhibited LT secretion through impaired Ca2(2+) influx and 5-lipoxygenase translocation to the nuclear membrane.

  20. Inhibitory activity of tryptanthrin on prostaglandin and leukotriene synthesis.

    Science.gov (United States)

    Danz, Henning; Stoyanova, Stefka; Thomet, Olivier A R; Simon, Hans-Uwe; Dannhardt, Gerd; Ulbrich, Holger; Hamburger, Matthias

    2002-10-01

    The indolo[2,1- b]quinazoline alkaloid tryptanthrin has previously been identified as the cyclooxygenase-2 (COX-2) inhibitory principle in the extract ZE550 prepared from the medicinal plant Isatis tinctoria (Brassicaceae). We here investigated the potential inhibitory activity of tryptanthrin and ZE550 on COX-2, COX-1 in cellular and cell-free systems. A certain degree of selectivity towards COX-2 was observed when COX-1-dependent formation of thromboxane B(2) (TxB(2)) in HEL cells and COX-2-dependent formation of 6-ketoprostaglandin F(1alpha) (6-keto-PGF(1alpha)) in Mono Mac 6 and RAW 264.7 cells were compared. Preferential inhibition of COX-2 by two orders of magnitude was found in phorbol myristate acetate (PMA) activated bovine aortic coronary endothelial cells (BAECs). Assays with purified COX isoenzymes from sheep confirmed the high selectivity towards COX-2. The leukotriene B(4) (LTB(4)) release from calcium ionophore-stimulated human granulocytes (neutrophils) was used as a model to determine 5-lipoxygenase (5-LOX) activity. Tryptanthrin and the extract ZE550 inhibited LTB(4) release in a dose dependent manner and with a potency comparable to that of the clinically used 5-LOX inhibitor zileuton.

  1. Side Effects of Leukotriene Receptor Antagonists in Asthmatic Children.

    Science.gov (United States)

    Erdem, Semiha Bahceci; Nacaroglu, Hikmet Tekin; Unsal Karkiner, Canan Sule; Gunay, Ilker; Can, Demet

    2015-10-01

    Leukotriene receptor antagonists (LTRAs) are drugs which have been widely used more than ten years. As the use of LTRAs increases, our knowledge with respect to their side effects increases as well. The objective of our study was to evaluat the observed side effects of LTRAs used in patients with astma. 1024 patients treated only with LTRAs owing to asthma or early wheezing were included in the study for a five-year period. The observed side effects of LTRAs in these patients were retrospectively investigated. The side effects were divided into two parts as psychiatric and non-psychiatric. Among the 1024 cases included in the study, 67.5% of the patients out of 41 with side effects were male, 32.5% were female and the average age was 6.5 years. The rate of patients with asthma was 63.41% and 36.58% of the patients had early wheezing. It was determined that sex, age and diagnosis (early wheezing or asthma) of the patients were ineffective in the emergence of side effects. The average period for the emergence of side effects was the first month. It was observed that hyperactivity was the most frequently observed psychiatric side effect and that abdominal pain was the non-psychiatric side effect. The side effects of LTRAs were common in children. Therefore, patients must be informed at the beginning of the treatment and they must be evaluated at certain intervals.

  2. Urinary leukotriene E4 at 12 months and influencing factors

    Directory of Open Access Journals (Sweden)

    K Stencel-Gabriel

    2016-01-01

    • 3.        Department of Gynecology, Obstetrics and Oncological Gynecology, Bytom, Medical University of Silesia       Corresponding author: Krystyna Stencel-Gabriel ul. Batorego 15 41-902 Bytom   Keywords: leukotriene E4, infants, allergy, urine.   Summary Objective LTE4 is the end point of cysLTs pathway and its only stable product. Its role was discussed in asthma and AEDS. We aimed to investigate the impact of genetic and environmental factors ( sex, maternal positive family atopy history, breastfeeding, passive smoking and pet exposure . 60 newborns ( including 30 boys were enrolled in the study. Each child was examined at 12 months and urine samples for urinary LTE4 measurement were collected. All samples were processed using ACETM Enzyme Immunoassay Kit ( Cayman Chemical, Ann Arbor, MI, USA . The mean level of urinary LTE4 at 12 months was 186,99 pg/ml ( median: 159,0; CI 95%: 157,79- 221,59 . The Shapiro- Wilk test showed that the distribution of the levels of urinary LTE4 were abnormal. 12- month- old girls had higher urinary LTE4 levels than boys ( mean: 270,50 vs. 193,55 , but maternal positive atopy history, pet exposure, tobacco smoking or length of breastfeeding had no impact on urinary LTE4 excretion. Conclusions In conclusion, most of genetic or environmental factors do not change levels of urinary LTE4 in infants.

  3. Factores que influyen en la emesis post-aturdimiento en bovinos

    OpenAIRE

    Ríos Rincón, Francisco Gerardo; Estrada Angulo, Alfredo; Hernández Bautista, Jorge; Pérez Linares, Cristina; Portillo Loera, Jesús José; Robles Estrada, Juan Carlos

    2012-01-01

    Para determinar el efecto del tiempo de espera pre-sacrificio, la efectividad del aturdimiento, el tipo de categoría comercial y la consistencia del contenido ruminal en la emesis durante el intervalo entre aturdimiento y desangrado en ganado bovino, se seleccionaron 9,446 canales en cuatro plantas procesadoras (P1, P2, P3, P4). El tiempo de espera pre-sacrificio se clasificó en: 1) menor a 3 h (T1); 2) de 3 a 12 h (T2); 3) mayor a 12 h (T3). El aturdimiento se registró como efectivo y no efe...

  4. Development of a sensitive and specific radioreceptor assay for leukotriene B4

    International Nuclear Information System (INIS)

    Kohi, F.; Agrawal, D.K.; Cheng, J.B.; Bewtra, A.; Townley, R.G.; Olesch, J.W.

    1988-01-01

    To establish a simple and sensitive quantitation of leukotriene B 4 (LTB 4 ), they developed a radioreceptor assay (RRA) using a highly specific [ 3 H]leukotriene B 4 ([ 3 H]LTB 4 ) binding to a guinea pig spleen homogenate. The assay detected LTB 4 levels as low as 0.12 pmol per tube. 50% inhibition of bound [ 3 H]LTB 4 was obtained by 2.5 nM of unlabeled LTB 4 . [ 3 H]LTB 4 competition studies indicated that 20-hydroxy-LTB 4 was 8 times, 6 trans-LTB 4 was 640 times and 20-carboxy-LTB 4 was 1000 times less effective than LTB 4 . The peptide leukotrienes C 4 , D 4 and E 4 showed no effect on [ 3 H]LTB 4 binding. Recovery rates averaged 97% after ethanol extraction and evaporation of known amounts of LTB 4 . The intra-assay coefficients of variation for three samples were 2.4%, 7.2% and 8.4%, respectively. This assay was validated by measuring LTB 4 released from human granulocytes stimulated with calcium ionophore A23187. The LTB 4 level was maximal at 10 min and decreased rapidly after 15 min. This radioreceptor assay for leukotriene B 4 is highly sensitive and is comparable to the reported sensitivity by radioimmunoassay. The method is simpler and less expensive than other methods such as high pressure liquid chromatography and is suitable for routine measurement of leukotriene B 4

  5. A prospective observational trial on emesis in radiotherapy: Analysis of 1020 patients recruited in 45 Italian radiation oncology centres

    International Nuclear Information System (INIS)

    Maranzano, Ernesto; De Angelis, Verena; Pergolizzi, Stefano; Lupattelli, Marco; Frata, Paolo; Spagnesi, Stefano; Frisio, Maria Luisa; Mandoliti, Giovanni; Malinverni, Giuseppe; Trippa, Fabio; Fabbietti, Letizia; Parisi, Salvatore; Di Palma, Annamaria; De Vecchi, Pietro; De Renzis, Costantino; Giorgetti, Celestino; Bergami, Tiziano; Orecchia, Roberto; Portaluri, Maurizio; Signor, Marco

    2010-01-01

    Purpose: A prospective observational multicentre trial was carried out to assess the incidence, pattern, and prognostic factors of radiation-induced emesis (RIE), and to evaluate the use of antiemetic drugs in patients treated with radiotherapy or concomitant radio-chemotherapy. The application in clinical practice of the Multinational Association of Supportive Care in Cancer guidelines was also studied. Materials and methods: Forty-five Italian radiation oncology centres took part in this trial. The accrual lasted for 3 consecutive weeks and only patients starting radiotherapy or concomitant radio-chemotherapy in this period were enrolled. Evaluation was based on diary card filled in daily by patients during treatment and one week after stopping it. Diary card recorded the intensity of nausea/vomiting and prophylactic/symptomatic antiemetic drug prescriptions. Results: A total of 1020 patients entered into the trial, and 1004 were evaluable. Vomiting and nausea occurred in 11.0% and 27.1% of patients, respectively, and 27.9% patients had both vomiting and nausea. In multifactorial analysis, the only statistically significant patient-related risk factors were concomitant chemotherapy and previous experience of vomiting induced by chemotherapy. Moreover, two radiotherapy-related factors were significant risk factors for RIE, the irradiated site (upper abdomen) and field size (>400 cm 2 ). An antiemetic drug was given only to a minority (17%) of patients receiving RT, and the prescriptions were prophylactic in 12.4% and symptomatic in 4.6%. Different compounds and a wide range of doses and schedules were used. Conclusions: These data were similar to those registered in our previous observational trial, and the radiation oncologists' attitude in underestimating RIE and under prescribing antiemetics was confirmed.

  6. Effects of acrolein on leukotriene biosynthesis in human neutrophils.

    Science.gov (United States)

    Berry, Karin A Zemski; Henson, Peter M; Murphy, Robert C

    2008-12-01

    Acrolein is a toxic, highly reactive alpha,beta-unsaturated aldehyde that is present in high concentrations in cigarette smoke. In the current study, the effect of acrolein on eicosanoid synthesis in stimulated human neutrophils was examined. Eicosanoid synthesis in neutrophils was initiated by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF) and subsequent stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP) and 5-lipoxygenase (5-LO) products in addition to small amounts of cyclooxygenase (COX) products were detected using LC/MS/MS. A dose-dependent decrease in the formation of 5-LO products was observed in GM-CSF/fMLP-stimulated neutrophils when acrolein (0-50 microM) was present with almost complete inhibition at > or = 25 microM acrolein. The production of COX products was not affected by acrolein in these cells. The effect of acrolein was examined on key parts of the eicosanoid pathway, such as arachidonic acid release, intracellular calcium ion concentration, and adenosine production. In addition, the direct effect of acrolein on 5-LO enzymatic activity was probed using a recombinant enzyme. Some of these factors were affected by acrolein but did not completely explain the almost complete inhibition of 5-LO product formation in GM-CSF/fMLP-treated cells with acrolein. In addition, the effect of acrolein on different stimuli that initiate the 5-LO pathway [platelet-activating factor (PAF)/fMLP, GM-CSF/PAF, opsonized zymosan, and A23187] was examined. Acrolein had no significant effect on the leukotriene production in neutrophils stimulated with PAF/fMLP, GM-CSF/ PAF, or OPZ. Additionally, 50% inhibition of the 5-LO pathway was observed in A23187-stimulated neutrophils. Our results suggest that acrolein has a profound effect on the 5-LO pathway in neutrophils, which may have implications in disease states, such as chronic obstructive pulmonary disease and other pulmonary disease, where both activated neutrophils and acrolein are

  7. Cysteinyl leukotriene signaling aggravates myocardial hypoxia in experimental atherosclerotic heart disease

    DEFF Research Database (Denmark)

    Nobili, Elena; Salvado, M Dolores; Folkersen, Lasse Westergaard

    2012-01-01

    Cysteinyl-leukotrienes (cys-LT) are powerful spasmogenic and immune modulating lipid mediators involved in inflammatory diseases, in particular asthma. Here, we investigated whether cys-LT signaling, in the context of atherosclerotic heart disease, compromises the myocardial microcirculation and ...

  8. Impact of botanical oils on polyunsaturated fatty acid metabolism and leukotriene generation in mild asthmatics

    Science.gov (United States)

    2013-01-01

    Background Dietary supplementation with botanical oils that contain n-6 and n-3 eighteen carbon chain (18C)-PUFA such as γ linolenic acid (GLA, 18:3n-6), stearidonic acid (SDA, 18:4n-3) and α linolenic acid (ALA, 18:3n-3) have been shown to impact PUFA metabolism, alter inflammatory processes including arachidonic acid (AA) metabolism and improve inflammatory disorders. Methods The diet of mild asthmatics patients was supplemented for three weeks with varying doses of two botanical seed oils (borage oil [Borago officinalis, BO] and echium seed oil [Echium plantagineum; EO]) that contain SDA, ALA and GLA. A three week wash out period followed. The impact of these dietary manipulations was evaluated for several biochemical endpoints, including in vivo PUFA metabolism and ex vivo leukotriene generation from stimulated leukocytes. Results Supplementation with several EO/BO combinations increased circulating 20–22 carbon (20–22C) PUFAs, including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and dihommo-gammalinolenic acid (DGLA), which have been shown to inhibit AA metabolism and inflammation without impacting circulating AA levels. BO/EO combinations also inhibited ex vivo leukotriene generation with some combinations attenuating cysteinyl leukotriene generation in stimulated basophils by >50% and in stimulated neutrophils by >35%. Conclusions This study shows that dietary supplementation with BO/EO alters 20–22C PUFA levels and attenuates leukotriene production in a manner consistent with a reduction in inflammation. PMID:24088297

  9. Stereoselective semi-hydrogenation and deuteration of a diacetylenic precursor of leukotriene B4 methyl ester

    International Nuclear Information System (INIS)

    Pontikis, R.; Le Merrer, Y.; Depezay, J.-C.; Petillot, Y.; Rousseau, B.; Beaucourt, J.P.

    1990-01-01

    [6,7,14,15- 2 H4]-Leukotriene B4 methyl ester was prepared by reduction with deuterium gas of a suitable precursor (deuterium incorporation > 90%). Several catalytic semi-hydrogenations were affected in order to determine the best conditions for the labeling step. (author)

  10. Exhaled Leukotrienes and Bronchial Responsiveness to Methacholine in Patients with Seasonal Allergic Rhinitis

    Czech Academy of Sciences Publication Activity Database

    Čáp, P.; Malý, Marek; Pehal, F.; Pelikán, Z.

    2009-01-01

    Roč. 102, č. 2 (2009), s. 103-109 ISSN 1081-1206 Grant - others:GA MZd(CZ) NL7024 Institutional research plan: CEZ:AV0Z10300504 Keywords : allergic rhinitis * asthma * breath condensate * leukotrienes * gas chromatography * mass spectrometry analysis Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 2.457, year: 2009

  11. Analysis of Exhaled Leukotrienes in Nonasthmatic Adult Patients with Seasonal Allergic Rhinitis

    Czech Academy of Sciences Publication Activity Database

    Čáp, P.; Pehal, F.; Malý, Marek; Chládek, J.

    2005-01-01

    Roč. 60, č. 2 (2005), s. 171-176 ISSN 0105-4538 Source of funding: V - iné verejné zdroje Keywords : allergic rhinitis * asthma * breath condensate * gas-chromatography/mass spectrometry analysis * leukotrienes Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 4.120, year: 2005

  12. Leukotrienes and 8-isoprostane in exhaled breath condensate in bronchoprovocation tests with occupational allergens

    Czech Academy of Sciences Publication Activity Database

    Klusáčková, P.; Lebedová, J.; Kačer, P.; Kuzma, Marek; Brabec, Marek; Pelclová, D.; Fenclová, Z.; Navrátil, Tomáš

    2008-01-01

    Roč. 78, 4-5 (2008), s. 281-292 ISSN 0952-3278 Institutional research plan: CEZ:AV0Z50200510; CEZ:AV0Z10300504; CEZ:AV0Z40400503 Keywords : occupational allergens * leukotrienes * 8-isoprostane Subject RIV: CC - Organic Chemistry Impact factor: 1.366, year: 2008

  13. Gas Chromatography/mass Spectrometry Analysis of Exhaled Leukotrienes in Asthmatic Patients

    Czech Academy of Sciences Publication Activity Database

    Čáp, P.; Chládek, J.; Pehal, F.; Malý, Marek; Petrů, V.; Barnes, P.J.; Montuschi, P.

    2004-01-01

    Roč. 59, č. 6 (2004), s. 465-470 ISSN 0040-6376 Source of funding: V - iné verejné zdroje Keywords : asthma * breath condensate * gas chromatography/mass spectrometry * leukotrienes Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 5.040, year: 2004

  14. Staphylococcus aureus and influenza A virus stimulate human bronchoalveolar cells to release histamine and leukotrienes

    DEFF Research Database (Denmark)

    Clementsen, P; Bisgaard, H; Pedersen, M

    1989-01-01

    persons were stimulated with Staph. aureus no release of leukotriene C4 was found. The mediator release caused by bacteria and virus might be of importance for the exacerbation of bronchial asthma in upper respiratory tract infections, since histamine is assumed to increase the epithelial permeability...

  15. SRS-A leukotrienes decrease the activity of human respiratory cilia

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, M

    1987-01-01

    We have studied the effects of the slow reacting substance of anaphylaxis (SRS-A) constituents leukotrienes (LT) C4 and D4 on the ciliary activity of human respiratory cells. The ciliary beat frequency on human nasal cells harvested by cell scraping from the inferior turbinate was measured...

  16. Leukotriene-mediated neuroinflammation, toxic brain damage, and neurodegeneration in acute methanol poisoning

    Czech Academy of Sciences Publication Activity Database

    Zakharov, S.; Kotíková, K.; Nurieva, O.; Hlušička, J.; Kačer, P.; Urban, P.; Vaněčková, M.; Seidl, Z.; Diblík, P.; Kuthan, P.; Navrátil, Tomáš; Pelclová, D.

    2017-01-01

    Roč. 55, č. 4 (2017), s. 249-259 ISSN 1556-3650 Institutional support: RVO:61388955 Keywords : brain damage * leukotrienes * methanol poisoning * Neuroinflammation * nontraumatic brain injury * sequelae of poisoning Subject RIV: CG - Electrochemistry OBOR OECD: Electrochemistry (dry cells, batteries, fuel cells, corrosion metals, electrolysis) Impact factor: 3.677, year: 2016

  17. 8-Isoprostane and leukotrienes in exhaled breath condensate in czech subjects with silicosis

    Czech Academy of Sciences Publication Activity Database

    Pelclová, D.; Fenclová, Z.; Kačer, P.; Navrátil, Tomáš; Kuzma, Marek; Lebedová, J.; Klusáčková, P.

    2007-01-01

    Roč. 45, č. 6 (2007), s. 766-774 ISSN 0019-8366 Grant - others:GA MZd NR8107 Institutional research plan: CEZ:AV0Z40400503; CEZ:AV0Z50200510 Keywords : silica * silicosis * 8-isoprostane * leukotrienes Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 0.792, year: 2007

  18. Development of an animal model for heavy ion radiation-induced nausea and vomiting

    International Nuclear Information System (INIS)

    Yamatodani, Atsushi; Yamamoto, Kouichi; Nohara, Kyoko

    2003-01-01

    Emesis is one of the most characteristic side effects of radiation therapy. Clinical and pharmacological findings indicate that the peripheral serotonergic pathway is predominantly involved in the development of radiation-induced emesis, but the precise etiology is still unknown. We previously demonstrated that the activation of the histaminergic neuron system in the brain is essential for the development of motion-induced emesis (motion sickness). In this study, we studied the effects of heavy-ion irradiation on the hypothalamic histamine release measured in vivo with a microdialysis method in mice. Total body irradiation at dose of 8 Gy (carbon ion: 290 MeV/u, 6 cm spread-out Bragg peak (SOBP)) did not cause any significant changes in the histamine release in mice. These findings indicate that the central histaminergic activation is not involved in the development of radiation-induced emesis in mice. (author)

  19. Hubungan Dukungan Sosial Keluarga Terhdap Emesis Gravidarum pada Ibu Hamil Trimester I di Puskesmas Bandar Khalifah Medan Tahun 2014

    OpenAIRE

    Remenda, Yuni Hijjah

    2015-01-01

    Latar beJakang : Dukungan sosial keluarga selama kehamilan dapat diberikan oleh pasangan wanita atau keluarga dan teman-temannya seeara dukugan nyata, pengharapan, emosional, dan inforrnasi. Tujuan Umum : Tujuan daTi penelitian ini adalah Untuk mengidentifikasi adanya Hubungan Dukungan Sosial Keluarga Terhadap Emesis Gravidarum Pada rbu Hamil Trimester I Di Puskesmas Bandar Khalifah Tahun 2014. Metodologi Penelitian Penelitian ini bersifat deskriptif korelasi dengan pendekat...

  20. Emesis ED50 of neutron irradiation and prophylactic effectiveness. Final report, 1 January 1979-31 December 1984

    Energy Technology Data Exchange (ETDEWEB)

    Cordts, R.E.; Ferlic, K.P.; Yochmowitz, M.G.; Mattsson, J.L.

    1985-08-01

    Two neutron emesis experiments were conducted at the Armed Forces Radiobiology Research Institute (AFRRI). In both experiments (described as Phase I and Phase II) the radiation dose required to cause emesis in 50% of subjects (ED50) was determined for both neutron reactor and gamma reactor source radiation. Emesis onset, offset and duration times post-exposure are reported. Neutrons were maximized from the reactor by passing the beam through a 15.25 cm (6 in.) thick lead wall to filter out gamma photons. Gamma rays were maximized by thermalizing neutrons in 30.5 cm (12 in.) of water, then absorbing the thermal neutrons in a gadolinium-cadmium shield. In Phase I, 28 dogs were exposed to radiation: 12 were exposed to gamma photons at the rate of 0.69 Gy/min and 16 were exposed to neutrons at 1.2 Gy/min. In Phase II, 58 dogs in 3 groups were exposed to radiation: 19 were exposed in the gamma group at 0.75 Gy/min, 20 were exposed in the undrugged neutron group at 1.62 Gy/min, and 19 were exposed in the drug-treated neutron group. The drugged group received, 40-min pre-exposure, a combination of thiethylperazine, promethazine, and cimetidine which was previously shown to raise a 60 Co gamma ED50 by 85%. The drugs were ineffective against neutron irradiation.

  1. Comparison of granisetron alone and granisetron plus dexamethasone in the prophylaxis of cytotoxic-induced emesis.

    Science.gov (United States)

    Carmichael, J.; Bessell, E. M.; Harris, A. L.; Hutcheon, A. W.; Dawes, P. J.; Daniels, S.; Bessel, E. M.

    1994-01-01

    Two hundred and seventy-eight adult chemonaive patients, receiving moderately emetogenic chemotherapy were randomly allocated to receive either intravenous (i.v.) granisetron 3 mg plus i.v. dexamethasone 8 mg or i.v. granisetron 3 mg plus i.v. placebo dexamethasone prior to chemotherapy. Eight-two per cent of all patients recruited were female, and 91% of all patients consumed less than 10 units of alcohol per week, suggesting a study population with an increased risk of nausea and vomiting. In the first 24 h 85% of patients who received granisetron plus dexamethasone were complete responders compared with 75.9% of the patients receiving granisetron alone (P = 0.053). There were statistically significant improvements in complete response over 7 days (P = 0.029) and in the numbers of patients receiving rescue antiemetic (P = 0.0004). Toxicity was minimal with no significant differences between treatment groups. These results confirm the antiemetic activity of granisetron and show that it has an additive effect in combination with dexamethasone. PMID:7981069

  2. Boerhaave's syndrome and tension pneumothorax secondary to Norovirus induced forceful emesis

    DEFF Research Database (Denmark)

    Venø, Søren; Eckardt, Jens

    2013-01-01

    Boerhaave's syndrome or spontaneous esophageal perforation is a rare condition, with high mortality. We describe a case of Boerhaave's syndrome presenting with tension pneumothorax. The patient was infected with Norovirus and developed Boerhaave's syndrome, initially thought to be gastroenteritis...

  3. Gamma-aminobutyric acid (GABA) and neuropeptides in neural areas mediating motion-induced emesis

    Science.gov (United States)

    Damelio, F.; Daunton, Nancy G.; Fox, Robert A.

    1991-01-01

    Immunocytochemical methods were employed to localize the neurotransmitter amino acid gamma-aminobutyric acid and the neuropeptides substance P and Met-enkephalin in the area postrema (AP), area subpostrema (ASP), nucleus of the tractus solitarius (NTS), dorsal motor nucleus of the vagus nerve (DMNV), and lateral vestibular nucleus (LVN). Glutamic acid decarboxylase immunoreactive (GAD-IR) terminals and fibers were observed in the AP and particularly in the ASP. A gradual decrease in the density of terminals was seen towards the solitary complex. The DMNV revealed irregularly scattered GAD-IR terminals within the neuropil or closely surrounding neuronal cell bodies. The LVN, particularly the dorsal division, showed numerous axon terminals which were mostly localize around large neurons and their proximal dendrites. Substance P immunoreactive (SP-IR) terminals and fibers showed high density in the solitary complex, in particular within the lateral division. The ASP showed medium to low density of SP-IR fibers and terminals. The AP exhibited a small number of fibers and terminals irregularly distributed. The DMNV revealed a high density of SP-IR terminals and fibers that were mainly concentrated in the periphery. Very few terminals were detected in the LVN. Met-enkephalin immunoreactive (Met-Enk-IR) fibers and terminals showed high density and uniform distribution in the DMNV. Scattered terminals and fibers were observed in the AP, ASP, and NTS (particularly the lateral division). The very few fibers were observed in the LVN surrounded the neuronal cell bodies. The present report is part of a study designed to investigate the interaction between neuropeptides and conventional neurotransmitters under conditions producing motion sickness and in the process of sensory-motor adaptation.

  4. In vivo formation of beta-oxidized metabolites of leukotriene E4 in the rat

    International Nuclear Information System (INIS)

    Perrin, P.; Zirrolli, J.; Stene, D.O.; Lellouche, J.P.; Beaucourt, J.P.; Murphy, R.C.

    1989-01-01

    Intraperitoneal administration of [ 3 H]-leukotriene E4 in the rat resulted in the appearance of radiolabel in urine and feces. Separation of polar urinary metabolites and chromatographic comparison of synthetic metabolites indicated the in vivo formation of omega-oxidized metabolites of LTE4 with sequential beta-oxidation. Furthermore, the metabolite identified as 16-carboxy-17,18,19,20-tetranor-14,15-dihydro-N-acetyl-LTE4 substantiates the biochemical pathway of beta-oxidation in vivo involving the 2,4-dienoyl CoA reductase as an integral step. These results substantiate beta-oxidation of sulfidopeptide leukotrienes in vivo and these metabolites account for some of the major urinary metabolites of this class of lipid mediator

  5. Promotor polymorphisms in leukotriene C4 synthase and risk of ischemic cerebrovascular disease

    DEFF Research Database (Denmark)

    Freiberg, J.J.; Tybjaerg-Hansen, A.; Sillesen, H.

    2008-01-01

    OBJECTIVE: Cysteinyl leukotrienes are involved in inflammation and possibly in early carotid atherosclerosis. We tested the hypothesis that the -444 A/C and -1072 G/A polymorphisms of the leukotriene C(4) synthase associate with risk of ischemic cerebrovascular disease. METHODS AND RESULTS: We...... genotyped 10 592 individuals from the Danish general population, the Copenhagen City Heart Study. During 24 years of follow-up, 557 individuals developed ischemic cerebrovascular disease. The allele frequency was 0.07 for -1072 A and 0.29 for -444 C. Cumulative incidence for ischemic cerebrovascular disease...... was higher for -1072 AA versus GG genotype (log-rank: P=0.002), and lower for -444 CC versus AA genotype (log-rank: P=0.008). Combined genotypes showed corresponding cumulative incidence differences (log-rank: P=0.003). Multifactorially adjusted hazard ratios for ischemic cerebrovascular disease were 2...

  6. Sesquiterpene glucosides from anti-leukotriene B4 release fraction of Taraxacum officinale.

    Science.gov (United States)

    Kashiwada, Y; Takanaka, K; Tsukada, H; Miwa, Y; Taga, T; Tanaka, S; Ikeshiro, Y

    2001-01-01

    Chemical examination of the MeOH extract of the root of Taraxacum officinale, which exhibited inhibitory activity on the formation of leukotriene B4 from activated human neutrophils, has resulted in the isolation of 14-O-beta-D-glucosyl-11,13-dihydro-taraxinic acid (1) and 14-O-beta-D-glucosyl-taraxinic acid (2). The absolute stereostructure of 1 has been established by X-ray chrystallographic examination.

  7. Blockade of leukotriene production by a single oral dose of MK-0591 in active ulcerative colitis

    DEFF Research Database (Denmark)

    Hillingsø, Jens; Kjeldsen, J; Laursen, L S

    1995-01-01

    dialysis fluid, ex vivo biosynthesis of LTB4 in whole blood, and urinary excretion of leukotriene E4 (LTE4) from 16 patients with mild to moderately active distally located ulcerative colitis were measured by use of radioimmunoassays in a double-blind, placebo-controlled parallel-design study before...... was unchanged. In whole blood, MK-0591 decreased ex vivo biosynthesis of LTB4 (p LTE4 was reduced by more than 85% (p

  8. Bilious emesis as presenting symptom of congenital diaphragmatic hernia in an 8-month-old

    Directory of Open Access Journals (Sweden)

    Daphney Clermont

    2017-12-01

    Full Text Available Although congenital diaphragmatic hernia (CDH primarily presents in either the prenatal or neonatal period, late presentation has a reported incidence of 2.5–25%. This case report describes an 8-month-old-male who presented to the emergency department with dehydration and a 24-h history of bilious emesis. Work-up led to the diagnosis of a left-sided Bochdalek CDH. He subsequently underwent laparoscopic diaphragmatic hernia repair with reduction of near-total length of incarcerated bowel. The patient had an uneventful recovery. Babies born with CDH are typically unstable at birth, and even with repair, the mortality rate remains high. However, in the case of delayed CDH diagnosis where there are no perinatal issues, surgical repair has very high success rates, provided that there are no complications regarding the delay. If there is not a high index of suspicion based on the patient's history and exam, delayed diagnosis and intervention with late CDH presentations can lead to complications which could otherwise be minimized. The purpose of this case report is to raise awareness and contribute to the growing knowledge about delayed CDH presentation among physicians and surgeons to facilitate early diagnosis and care of a morbid yet manageable condition.

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

    International Nuclear Information System (INIS)

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

    1988-01-01

    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 ferret was similar to that in the rat. In animals with whole-body exposure to moderate levels of radiation (4 Gy of 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

  10. Comparison of granisetron and metoclopramide in the treatment of pain and emesis in migraine patients: A randomized controlled trial study

    Directory of Open Access Journals (Sweden)

    Hassan Amiri

    2017-06-01

    Full Text Available Objectives: One of the irritating features of migraine is emesis that can compromise taking oral medications. We designed this study to compare the effectiveness of granisetron and metoclopramide in reducing pain and treating emesis in migraine patients. Methods: We included a total of 148 patients with migraine headache presenting to two referral hospitals in a prospective, double-blinded randomized controlled trial. We compared the effect of granisetron (2 mg intravenous with metoclopramide (10 mg intravenous. Pain intensity and emesis episodes were recorded before drug administration, one, two and four 4 h after drug administration. Results: Of the 148 patients, 47 were male and 101 were female. 75 patients received granisetron and 73 metoclopramide. Mean pain intensity before the administration of the medications was 7.67 ± 1.30 in granisetron group and 7.68 ± 1.13 in metoclopramide group with an insignificant difference. Mean pain intensity at one, two, and 4 h after drug administration was 3.20 ± 1.37, 2.39 ± 1.28, and 1.31 ± 0.52 in granisetron group and 5.04 ± 1.77, 4.1 ± 1.8, and 1.56 ± 0.68 in metoclopramide group (P = 0.03. Mean emesis episodes before drug administration were 1.85 ± 0.81 and 1.80 ± 0.77 in granisetron and metoclopramide groups, respectively. These episodes were 1.33 ± 0.66, 0.25 ± 0.49, and 0.04 ± 0.19 in granisetron group and 1.38 ± 0.73, 0.21 ± 0.47, and 0.41 ± 0.19 in metoclopramide group at one, two, and 4 h after the drug administration (P = 0.7. Conclusion: To came in conclusion, compared to metoclopramide, granisetron is a better choice in acute migraine ATTACK because it decreases the patients' pain as well as their emesis. Keywords: Migraine, Headache, Granisetron, Metoclopramide, Pain

  11. Exhaled breath condensate pH and cysteinyl leukotriens in patients with chronic cough secondary to acid gastroesophageal reflux.

    Science.gov (United States)

    Heffler, Enrico; Crimi, Claudia; Brussino, Luisa; Nicola, Stefania; Sichili, Stefania; Dughera, Luca; Rolla, Giovanni; Crimi, Nunzio

    2016-12-22

    Chronic cough is one of the most common clinical problems and it may be secondary to different stimuli and diseases, including low-level physical and chemical stimulation of the esophageal-bronchial reflex, suggestive of cough-reflex hyperresponsiveness, in patients with gastroesophageal reflux; however, it is still debated whether gastroesophageal reflux could induce airway inflammation and acidification. The aim of this study was to investigate airway pH and cysteynil-leukotrienes (Cys-LTs) concentration (a marker of airway inflammation) in exhaled breath condensate (EBC). Patients with chronic cough and for which all known causes, excluding gastroesophageal reflux, had been investigated and ruled out, were enrolled in the study. All patients underwent 24 h pH monitoring, and EBC was collected to assess pH and Cys-LTs concentration. Forty-five patients were included in the study and those with gastroesophageal reflux had significantly lower EBC-pH and higher concentration of EBC-Cys-LTs. There was a linear inverse correlation between EBC-pH values and EBC-Cys-LTs logarithmically transformed, and a multivariate analysis confirmed that the only significant determinat variable of EBC-Cys-LTs was the presence of gastroesophageal reflux. This study adds knowledge on possible mechanisms related to chronic cough associated with gastroesophageal reflux, which seems to be strictly dependent on airway acidification and the production of Cys-LTs, therefore suggesting an underlying neurogenic inflammation with tachykinins involvement.

  12. Molecular mechanisms of the synergy between cysteinyl-leukotrienes and receptor tyrosine kinase growth factors on human bronchial fibroblast proliferation

    Directory of Open Access Journals (Sweden)

    Hajime Yoshisue

    2006-12-01

    Full Text Available We have reported that cysteinyl-leukotrienes (cys-LTs synergise not only with epidermal growth factor (EGF but also with platelet-derived growth factor (PDGF and fibroblast growth factor (FGF to induce mitogenesis in human bronchial fibroblasts. We now describe the molecular mechanisms underlying this synergism. Mitogenesis was assessed by incorporation of [3H]thymidine into DNA and changes in protein phosphorylation by Western blotting. Surprisingly, no CysLT receptor antagonists (MK-571, montelukast, BAY u9773 prevented the synergistic mitogenesis. LTD4 did not cause phosphorylation of EGFR nor did it augment EGF-induced phosphorylation of EGFR, and the synergy between LTD4 and EGF was not blocked by the metalloproteinase inhibitor GM6001 or by an HB-EGF neutralising antibody. The EGFR-selective kinase inhibitor, AG1478, suppressed the synergy by LTD4 and EGF, but had no effect on the synergy with PDGF and FGF. While inhibitors of mitogen-activated protein kinase, phosphatidylinositol 3-kinase and protein kinase C (PKC prevented the synergy, these drugs also inhibited mitogenesis elicited by EGF alone. In contrast, pertussis toxin (PTX efficiently inhibited the potentiating effect of LTD4 on EGF-induced mitogenesis, as well as that provoked by PDGF or FGF, but had no effect on mitogenesis elicited by the growth factors alone. Whereas LTD4 alone did not augment phosphorylation of extracellular signal-regulated kinase (Erk-1/2 and Akt, it increased phosphorylation of PKC in a Gi-dependent manner. Addition of LTD4 prolonged the duration of EGF-induced phosphorylation of Erk-1/2 and Akt, both of which were sensitive to PTX. The effect of cys-LTs involves a PTX-sensitive and PKC-mediated intracellular pathway leading to sustained growth factor-dependent phosphorylation of Erk-1/2 and Akt.

  13. The effect of the leukotriene antagonist pranlukast on pediatric acute otitis media.

    Science.gov (United States)

    Nakamura, Yoshihisa; Hamajima, Yuki; Suzuki, Motohiko; Esaki, Shinichi; Yokota, Makoto; Oshika, Masanori; Takagi, Ippei; Yasui, Keiko; Miyamoto, Naoya; Sugiyama, Kazuko; Nakayama, Meiho; Murakami, Shingo

    2016-08-01

    Conventional treatment for acute otitis media mainly targets bacteria with antibiotics, neglecting to control for mediators of inflammation. Mediators of inflammation, such as leukotrienes, have been identified in patients with acute otitis media (AOM) or subsequent secretory otitis media (SOM). They can cause functional eustachian tube dysfunction or increase mucous in the middle ear, causing persistent SOM following AOM. The objective of the present study was to evaluate whether or not administration of pranlukast, a widely used leukotriene C4, D4, and E4 antagonist, together with antibiotics could inhibit the progression to SOM. Children with AOM, who were from two to 12 years old, were randomly divided into two groups as follows: a control group in which 50 patients received antibiotic-based conventional treatment according to guidelines for treating AOM proposed by the Japan Otological Society (version 2006); and a pranlukast group, in which 52 patients were administered pranlukast for up to 28 days as well as given conventional treatment. Cases were regarded as persistent SOM when a tympanogram was type B or C2 four weeks after treatment was initiated. Two patients in the pranlukast group and 3 patients in the control group were excluded because they relapsed AOM within 28 days after initial treatment. Therefore, the analysis included 50 and 47 subjects in the pranlukast and control groups, respectively. The percentage of patients diagnosed with persistent SOM (22.0%) was significantly smaller in the pranlukast group compared with the control group (44.7%) (p = 0.018, chi-squared test). The results indicate that combined treatment of AOM with antibiotics and a leukotriene antagonist to control inflammation is useful for preventing progression to persistent SOM. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. A convenient synthesis of deuterated leukotriene A sub 4 methyl ester

    Energy Technology Data Exchange (ETDEWEB)

    Bestmann, H.J.; Roeder, T. (Erlangen-Nuernberg Univ., Erlangen (Germany, F.R.). Inst. fuer Organische Chemie); Meese, C.O. (Fischer-Bosch-Inst. fuer Klinische Pharmakologie, Stuttgart (Germany, F.R.))

    1989-11-01

    2,2,3,3-({sup 2}H{sub 4})-1-Iodopentane was prepared in four steps from propargyl alcohol and used in the C-alkylation of the THP-protected 3-butyne-1-ol. Subsequent protective group removal, semi-deuteration of the acetylenic alcohol and further transformation by known methods afforded the labelled key reagent 3,4,6,6,7,7-({sup 2}H{sub 6})-(Z)-(3-nonen-1-yl)triphenylphosphonium iodide. Wittig olefination of epoxy dienal with the ylide generated from the latter completed the convenient synthesis of hexadeuterated leukotriene A{sub 4} methyl ester. (author).

  15. Breath condensate levels of 8-isoprostane and leukotriene B4 after ozone inhalation are greater in sensitive versus nonsensitive subjects.

    Science.gov (United States)

    Alfaro, Mario F; Walby, William F; Adams, William C; Schelegle, Edward S

    2007-01-01

    Ozone (O3) inhalation induces pulmonary function decrements and inflammation. The present study was designed to determine if a relationship exists between O3 induced pulmonary function changes and the presence of inflammatory markers as measured in exhaled breath condensates (EBCs) obtained from O3-sensitive and nonsensitive human subjects. Eight healthy adult volunteers (4 males/4 females, age 18 to 30 years) were studied, characterized as to their ozone sensitivity and placed into 2 groups (sensitive and nonsensitive) with each group having 2 males and 2 females. Subjects completed a 20-minute EBC collection and pulmonary function test (PFT) prior to a single 60-minute bout of cycle ergometer exercise (V(E) = 50-55 L/min) while breathing filtered air (FA) or 0.35 ppm O3. Subjective symptom scores (SSSs) were collected at 6, 20, 40, and 60 minutes during exposure. An immediate postexposure PFT was performed followed by an EBC collection. Subjective symptom scores, EBCs, and PFTs were collected at 1, 4 and 8 hours post exposure. EBCs were analyzed for prostaglandin E2 (PGE2), leukotriene B4 (LTB4), 8-isoprostane, and total nitric oxide (NO) metabolites (nitrate + nitrite content). Sensitive subjects, breathing O3, had significantly greater functional decrements in PFTs, increased SSSs, and increased rapid shallow breathing as well as elevated levels of 8-isoprostane and LTB4 in EBCs compared to those breathing FA. In addition, there were significant increases in nitrate + nitrite content in both sensitive and nonsensitive subjects breathing O3 compared to FA. These results indicate that sensitive subjects have elevated arachidonic acid metabolites in EBCs compared to nonsensitive subjects after O3 inhalation.

  16. Surveying the effect of a self-care education program on severity of nausea and emesis in colorectal cancer patients under chemotherapy

    Directory of Open Access Journals (Sweden)

    Karimi S

    2017-08-01

    Full Text Available Saba Karimi,1 Behnam Reza Makhsosi,2 Seyed Jalil Seyedi-Andi,3 Maryam Behzadi,4 Yasaman Moghofeh,5 Kourosh Mohammadinasrabadi,1 Alireza Abdi,1 Pegah Ahmadi1 1School of Nursing and Midwifery, 2Surgical Department, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, 3Social Determinants of Health Research Center, Babol University of Medical Sciences, Babol, 4Taleghani Hospital, 5Imam Khomeini Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran Background and objective: Colorectal cancer is one of the main causes of mortality in both developed and developing countries, including Iran. One of the treatments available for colorectal cancer is chemotherapy, of which nausea and emesis are the side effects. Owing to problems in controlling the side effects, a combination of medicine and non-medicine interventions is usually used. Self-care is one of the non-medicine interventions in this regard. The present study was aimed at surveying the effect of a self-care education program on severity of nausea and emesis in colorectal cancer patients under chemotherapy.Methods: A semi-experimental study was carried out in Imam Reza Hospital of Kermanshah, Iran. The sample group comprised 52 patients with colorectal cancer under chemotherapy. Data gathering tools included a demographics questionnaire and Morrow Assessment of Nausea and Emesis. To control intensity of nausea and emesis, a package of self-care measures including muscular progressive relaxation, music, and education on nutrition was used. Afterward, the collected data were analyzed using statistical tests such as Shapiro–Wilk test (to check normal distribution of the data, Mann–Whitney U test, Wilcoxon test, and chi-square test with the help of SPSS 20.Results: The results showed a considerable decrease in intensity and frequency of nausea and emesis after the intervention. The p-value of Mann–Whitney U test results with regard to intensity of nausea in

  17. Characterization of guinea pig myocardial leukotriene C4 binding sites. Regulation by cations and sulfhydryl-directed reagents

    International Nuclear Information System (INIS)

    Hogaboom, G.K.; Mong, S.; Stadel, J.M.; Crooke, S.T.

    1985-01-01

    Using [ 3 H]leukotriene C4 (LTC4) and radioligand-binding techniques, specific leukotriene C4 binding sites have been identified in membranes derived from guinea pig ventricular myocardium. High performance liquid chromatography analyses indicated that, in the presence of the gamma-glutamyl transpeptidase inhibitor L-serine-borate (80 mM), less than 2% of membrane-bound [ 3 H]LTC4 was converted at 20 degrees to [ 3 H]leukotriene D4 or [ 3 H]leukotriene E4. The specific binding of 4 nM [ 3 H]LTC4, in the presence of 80 mM L-serine-borate, reached a stable steady state within 15 min at 20 degrees (pH 7.5). A monophasic Scatchard plot of saturation binding data yielded a dissociation constant (Kd) of 27.5 +/- 6.0 nM and a maximum number of binding sites (Bmax) of 19.9 +/- 5.2 pmol/mg of membrane protein. Competition binding studies of [ 3 H]LTC4 with synthetic leukotriene C4, leukotriene D4, and leukotriene E4 and the putative peptidoleukotriene antagonists FPL 55712, SKF 88046, and 4R-hydroxy-5S-1-cysteinylglycine-6Z-nonadecanoic acid revealed an order of potency of leukotriene C4 much greater than 4R-hydroxy-5S-1-cysteinylglycine-6Z-nonadecanoic acid greater than SKF 88046 greater than LTE4 greater than LTD4 greater than FPL 55712. The specific [ 3 H]LTC4 binding was stimulated by the divalent cations Ca2+, Mg2+, and Mn2+ and to a lesser degree by the monovalent cations Na+, K+, Li+, and NH4+. CaCl2 (3 mM) and NaCl (150 mM) stimulated the LTC4 binding by increasing the Bmax to 42.6 +/- 5.9 and 35.0 +/- 2.0 pmol/mg, respectively, but had minimal effects on Kd

  18. Leukotriene B4 receptors on guinea pig alveolar eosinophils

    International Nuclear Information System (INIS)

    Maghni, K.; de Brum-Fernandes, A.J.; Foeldes-Filep, E.G.; Gaudry, M.; Borgeat, P.; Sirois, P.

    1991-01-01

    The existence of receptors for LTB4 on highly purified guinea pig alveolar eosinophils was investigated. Massive infiltration of eosinophils in alveolar spaces was induced in guinea pigs by i.v. injections of Sephadex beads G50 (16 mg/kg). Alveolar eosinophils (50 x 10(6) cells) were purified to approximately 98% by Percoll continuous density gradient centrifugation. The binding studies indicated that alveolar eosinophils bind LTB4 in a saturable, reversible and specific manner. Scatchard analysis indicated the existence of high-affinity binding sites (Kd1 = 1.00 ± 0.22 nM; Bmax1 = 966 ± 266 sites/cell) and low-affinity binding sites (Kd2 = 62.5 ± 8.9 nM; Bmax2 = 5557 ± 757 sites/cell). The metabolism of LTB4 by alveolar eosinophils in binding conditions was assessed by RP-HPLC and no significant degradation of [3H]LTB4 was observed. LTB4 dose-dependently stimulated eosinophil migration in both chemokinesis and chemotaxis assays with an EC50 value of 1.30 ± 0.14 and 18.14 ± 1.57 nM, respectively. LTB4 caused a dose-dependent increase in the production of superoxide anion with an apparent EC50 value of 50 x 10(-9) M in the authors experimental conditions. LTB4 also induced a dose-dependent increase in the generation of TxA2 with an EC50 value of 46.2 x 10(-9) M. Taken together, their results demonstrated that guinea pig alveolar eosinophils express two classes of specific receptors for LTB4. The high-affinity binding sites seem associated to chemokinesis and chemotaxis whereas the low-affinity binding sites seem associated to superoxide anion production and generation of TxA2. The existence of LTB4 receptors in eosinophils could explain the presence of these cells in hypersensitivity reactions

  19. Non-genomic action of beclomethasone dipropionate on bronchoconstriction caused by leukotriene C4 in precision cut lung slices in the horse

    Directory of Open Access Journals (Sweden)

    Fugazzola Maria

    2012-09-01

    Full Text Available Abstract Background Glucocorticoids have been proven to be effective in the therapy of recurrent airway obstruction (RAO in horses via systemic as well as local (inhalative administration. Elective analysis of the effects of this drug on bronchoconstriction in viable lung tissue offers an insight into the mechanism of action of the inflammatory cascade occurring during RAO which is still unclear. The mechanism of action of steroids in treatment of RAO is thought to be induced through classical genomic pathways. We aimed at electively studying the effects of the glucocorticoid beclomethasone dipropionate on equine precision-cut lung slices (PCLS. PCLS were used to analyze ex-vivo effects of beclomethasone on inhibiting bronchoconstriction in the horse. The inhibiting effect was measured through instillation of a known mediator of inflammation and bronchoconstriction, leukotriene C4. For this, the accessory lobes of 13 horses subjected to euthanasia for reasons unrelated to the respiratory apparatus were used to obtain viable lung slices. Results After 30 minutes of PCLS incubation, beclomethasone showed to significantly inhibit the contraction of the bronchioles after instillation with leukotriene C4. The EC50 values of the two contraction curves (LTC4 with and without BDP differed significantly from each other (p = 0.002. The possibility of a non-genomic rapid mechanism of action seems likely since transcriptional activities require a longer lag period. Conclusions In human neuroendocrinology, high levels of glucocorticoids have been proven to function via a non-genomic mechanism of membrane receptors. The concentration of beclomethasone used on the lung slices in our study can be considered as high. This allows speculation about similar rapid non-genomic mechanisms of high-dosage inhaled glucocorticoids in the lower airways of horses. However, further assessment on a molecular basis is needed to confirm this.

  20. Selectivity of recombinant human leukotriene D(4), leukotriene B(4), and lipoxin A(4) receptors with aspirin-triggered 15-epi-LXA(4) and regulation of vascular and inflammatory responses.

    Science.gov (United States)

    Gronert, K; Martinsson-Niskanen, T; Ravasi, S; Chiang, N; Serhan, C N

    2001-01-01

    Aspirin-triggered lipoxin A(4) (ATL, 15-epi-LXA(4)) and leukotriene D(4) (LTD(4)) possess opposing vascular actions mediated via receptors distinct from the LXA(4) receptor (ALX) that is involved in leukocyte trafficking. Here, we identified these receptors by nucleotide sequencing and demonstrate that LTD(4) receptor (CysLT(1)) is induced in human vascular endothelia by interleukin-1beta. Recombinant CysLT(1) receptor gave stereospecific binding with both [(3)H]-LTD(4) and a novel labeled mimetic of ATL ([(3)H]-ATLa) that was displaced with LTD(4) and ATLa ( approximately IC(50) 0.2 to 0.9 nmol/L), but not with a bioinactive ATL isomer. The clinically used CysLT(1) receptor antagonist, Singulair, showed a lower rank order for competition with [(3)H]-ATLa (IC(50) approximately 8.3 nmol/L). In contrast, LTD(4) was an ineffective competitive ligand for recombinant ALX receptor with [(3)H]-ATLa, and ATLa did not compete for [(3)H]-LTB(4) binding with recombinant LTB(4) receptor. Endogenous murine CysLT(1) receptors also gave specific [(3)H]-ATLa binding that was displaced with essentially equal affinity by LTD(4) or ATLa. Systemic ATLa proved to be a potent inhibitor (>50%) of CysLT(1)-mediated vascular leakage in murine skin (200 microg/kg) in addition to its ability to block polymorphonuclear leukocyte recruitment to dorsal air pouch (4 microg/kg). These results indicate that ATL and LTD(4) bind and compete with equal affinity at CysLT(1), providing a molecular basis for aspirin-triggered LXs serving as a local damper of both vascular CysLT(1) signals as well as ALX receptor-regulated polymorphonuclear leukocyte traffic.

  1. Resveratrol, a Red Wine Polyphenol, Suppresses Pancreatic Cancer by Inhibiting Leukotriene A4 Hydrolase

    Science.gov (United States)

    Oi, Naomi; Jeong, Chul-Ho; Nadas, Janos; Cho, Yong-Yeon; Pugliese, Angelo; Bode, Ann M.; Dong, Zigang

    2016-01-01

    The anticancer effects of red wine have attracted considerable attention. Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a well-known polyphenolic compound of red wine with cancer chemopreventive activity. However, the basis for this activity is unclear. We studied leukotriene A4 hydrolase (LTA4H) as a relevant target in pancreatic cancer. LTA4H knockdown limited the formation of leukotriene B4 (LTB4), the enzymatic product of LTA4H, and suppressed anchorage-independent growth of pancreatic cancer cells. An in silico shape similarity algorithm predicted that LTA4H might be a potential target of resveratrol. In support of this idea, we found that resveratrol directly bound to LTA4H in vitro and in cells and suppressed proliferation and anchorage-independent growth of pancreatic cancer by inhibiting LTB4 production and expression of the LTB4 receptor 1 (BLT1). Notably, resveratrol exerted relatively stronger inhibitory effects than bestatin, an established inhibitor of LTA4H activity, and the inhibitory effects of resveratrol were reduced in cells where LTA4H was suppressed by shRNA-mediated knockdown. Importantly, resveratrol inhibited tumor formation in a xenograft mouse model of human pancreatic cancer by inhibiting LTA4H activity. Our findings identify LTA4H as a functionally important target for mediating the anticancer properties of resveratrol. PMID:20952510

  2. Stereoselective semi-hydrogenation and deuteration of a diacetylenic precursor of leukotriene B sub 4 methyl ester

    Energy Technology Data Exchange (ETDEWEB)

    Pontikis, R.; Le Merrer, Y.; Depezay, J.-C. (U.D.C. CNRS-INSERM (URA 400), 75, Paris (France). Lab. de Chimie et Biochimie Pharamacologiques et Toxicologiques); Petillot, Y.; Rousseau, B.; Beaucourt, J.P. (CEA Centre d' Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France). Service des Molecules Marquees)

    1990-10-01

    (6,7,14,15-{sup 2}H4)-Leukotriene B4 methyl ester was prepared by reduction with deuterium gas of a suitable precursor (deuterium incorporation > 90%). Several catalytic semi-hydrogenations were affected in order to determine the best conditions for the labeling step. (author).

  3. Determination of cysteinyl leukotrienes in exhaled breath condensate: Method combining immunoseparation with LC-ESI-MS/MS

    Czech Academy of Sciences Publication Activity Database

    Syslová, K.; Kačer, P.; Vilhanová, B.; Kuzma, Marek; Lipovová, P.; Fenclová, Z.; Lebedová, J.; Pelclová, D.

    2011-01-01

    Roč. 879, č. 23 (2011), s. 2220-2228 ISSN 1570-0232 R&D Projects: GA MZd NS10298 Keywords : Cysteinyl leukotriene * Exhaled breath condensate * Immunoseparation Subject RIV: CE - Biochemistry Impact factor: 2.888, year: 2011

  4. Inhibition of cisplatin-induced vomiting by selective 5-hydroxytryptamine M-receptor antagonism.

    OpenAIRE

    Miner, W. D.; Sanger, G. J.

    1986-01-01

    MDL 72222, the selective 5-hydroxytryptamine (5-HT) M-receptor antagonist, prevented or reduced cisplatin-induced emesis in ferrets. It is suggested that cisplatin-induced, and possibly other cytotoxic drug-induced vomiting may involve a 5-HT M-receptor mechanism.

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

    Science.gov (United States)

    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.

  6. The linkage between Churg-Strauss syndrome and leukotriene receptor antagonists: fact or fiction?

    Science.gov (United States)

    McDanel, Deanna L; Muller, Barbara A

    2005-01-01

    Epidemiologic evidence has shown that the worldwide prevalence of asthma is increasing. The leukotriene receptor antagonists (LTRAs) represent a new class of therapy for asthma. They have been developed in the last decade and play a pivotal steroid-sparing role in treating the inflammatory component of asthma. Consequently, reports of Churg-Strauss syndrome (CSS), a rare form of systemic vasculitis, have been recognized as a potential side effect in individuals with moderate to severe asthma on LTRA therapy. The serious nature of this disorder is worthy of prompt recognition by clinicians and aggressive therapy to avoid the subsequent longstanding effects of vasculitis. To validate the postulated linkage between the LTRAs and CSS, this review comprehensively evaluates reported cases in the literature and supports a pathophysiological relationship between the LTRAs and the development of CSS. PMID:18360552

  7. Release of leukotriene C4 from human polymorphonuclear leucocytes as determined by radioimmunoassay

    International Nuclear Information System (INIS)

    Aehringhaus, U.; Woelbling, R.H.; Peskar, B.M.; Peskar, B.A.; Koenig, W.; Patrono, C.

    1982-01-01

    Rabbits were immunized with a conjugate of leukotriene (LT)C 4 and bovine serum albumin prepared by coupling the single free amino group of the hapten to the protein using gluteraldehyde. Binding of [ 3 H]LTC 4 to the antibodies obtained is inhibited by 50% with 1.5 ng LTC 4 . The relative cross-section of LTD 4 is 16% and of LTC 4 -methyl ester 3.6%. The validity of the radioimmunoassay was demonstrated by comparison with bioassay using the isolated guinea pig ileum. Using the radioimmunoassay it could be shown that endogenous LTC 4 is released in a dose-dependent manner by human polymorphonuclear leucocytes stimulated with the divalent cation ionophore A23187. (Auth.)

  8. Immunomagnetic molecular probe with UHPLC-MS/MS: A promising way for reliable bronchial asthma diagnostics based on quantification of cysteinyl leukotrienes

    Czech Academy of Sciences Publication Activity Database

    Syslová, K.; Boehmová, A.; Demirbag, E.; Šimková, K.; Kuzma, Marek; Pelclová, D.; Sedlák, V.; Čáp, P.; Martásek, P.; Kačer, P.

    81-82, AUG 2013 (2013), s. 108-117 ISSN 0731-7085 Institutional support: RVO:61388971 Keywords : Cysteinyl leukotrienes * Immunomagnetic separation * UHPLC-MS Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.829, year: 2013

  9. Leukotrienes B4, C4, D4 and E4 in the Exhaled Breath Condensate (EBC), Blood and Urine in Patients with Pneumoconiosis

    Czech Academy of Sciences Publication Activity Database

    Pelclová, D.; Fenclová, Z.; Vlčková, Š.; Lebedová, J.; Syslová, K.; Pecha, O.; Běláček, J.; Navrátil, Tomáš; Kuzma, Marek; Kačer, P.

    2012-01-01

    Roč. 50, č. 4 (2012), s. 299-306 ISSN 0019-8366 Institutional support: RVO:61388955 ; RVO:61388971 Keywords : leukotrienes * Lung fibrosis * exhaled breath condensate Subject RIV: CG - Electrochemistry Impact factor: 0.870, year: 2012

  10. (3H)leukotriene B4 binding to the guinea pig spleen membranes: a rich tissue source for a high affinity leukotriene B4 receptor site

    International Nuclear Information System (INIS)

    Cheng, J.B.; Kohi, F.; Townley, R.G.

    1986-01-01

    To select a tissue rich for the high affinity leukotriene (LT)B 4 receptor site, they compared binding of 1 nM ( 3 H)LTB 4 (180 Ci/mmol) to the crude membrane preparations of guinea pig spleen, thymus, lung, uterus, bladder, brain, adrenal gland, small intestine, liver, kidney and heart. They found that the membrane preparations from spleen contained the highest binding activity per mg protein. They characterized the LTB 4 binding to the spleen preparation in detail. LTB 4 binding was rapid, reversible, stereoselective and saturable. The data from equilibrium experiments showed a linear Scatchard plot with a K/sub d/ of 1.6 nM and a binding site density of 259 fmol/mg prot. The rank order of agents competing for spleen ( 3 H)LTB 4 binding at 25 0 C was: LTB 4 (K/sub i/ = 2.8 nM) > 20-OH-LTB 4 (23 nM) > LTA 4 (48 nM) > LTA 4 methyl ester (0.13 μM) > 20-COOH-LTB 4 (> 6.6 μM) ≥ arachidonic acid (0.15 mM) similarly ordered FPL-55,712 (0.11 mM). At 4 0 C, LTB 4 (2.3 nM) competed at least 10x more effectively than 20-OH-LTB 4 (29 nM) and 20-COOH-LTB 4 (> 6.6 μM). HPLC analysis indicated that incubation of 84 ng LTB 4 with the spleen membrane at 25 0 C did not result in the formation of 20-OH-LTB 4 ( 3 H)LTB 4 receptor binding sites

  11. Identification of leukotriene D4 specific binding sites in the membrane preparation isolated from guinea pig lung

    International Nuclear Information System (INIS)

    Mong, S.; Wu, H.L.; Clark, M.A.; Stadel, J.M.; Gleason, J.G.; Crooke, S.T.

    1984-01-01

    A radioligand binding assay has been established to study leukotriene specific binding sites in the guinea pig and rabbit tissues. Using high specific activity [ 3 H]-leukotriene D4 [( 3 H]-LTD4), in the presence or absence of unlabeled LTD4, the diastereoisomer of LTD4 (5R,6S-LTD4), leukotriene E4 (LTE4) and the end-organ antagonist, FPL 55712, the authors have identified specific binding sites for [ 3 H]-LTD4 in the crude membrane fraction isolated from guinea pig lung. The time required for [ 3 H]-LTD4 binding to reach equilibrium was approximately 20 to 25 min at 37 degrees C in the presence of 10 mM Tris-HCl buffer (pH 7.5) containing 150 mM NaCl. The binding of [ 3 H]-LTD4 to the specific sites was saturable, reversible and stereospecific. The maximal number of binding sites (Bmax), derived from Scatchard analysis, was approximately 320 +/- 200 fmol per mg of crude membrane protein. The dissociation constants, derived from kinetic and saturation analyses, were 9.7 nM and 5 +/- 4 nM, respectively. The specific binding sites could not be detected in the crude membrane fraction prepared from guinea pig ileum, brain and liver, or rabbit lung, trachea, ileum and uterus. In radioligand competition experiments, LTD4, FPL 55712 and 5R,6S-LTD4 competed with [ 3 H]-LTD4. The metabolic inhibitors of arachidonic acid and SKF 88046, an antagonist of the indirectly-mediated actions of LTD4, did not significantly compete with [ 3 H]-LTD4 at the specific binding sites. These correlations indicated that these specific binding sites may be the putative leukotriene receptors in the guinea-pig lung

  12. The Role of PPAR Receptors and Leukotriene B4 Receptors in Mediating the Effects of LY293111 in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Thomas E. Adrian

    2008-01-01

    Full Text Available Pancreatic cancer is a devastating disease in which current therapies are inadequate. Separate lines of research have identified the 5-lipoxygenase/leukotriene B4 receptor pathway and the PPAR pathway as potential targets for prevention or treatment of this disease. LY293111 was originally designed as a potent leukotriene B4 receptor antagonist for treatment of inflammatory conditions. LY293111 was also known to have inhibitory effects on 5-lipoxygenase, which is upstream of the production of leukotrienes. LY293111 was shown to have potent anticancer effects in pancreatic cancer and several other solid malignancies, where it caused cell cycle arrest and marked apoptosis. Subsequently, it came to light that LY293111 exhibited PPAR agonist activity in addition to its effects on the 5-lipoxygenase pathway. This raises the question of which of the two targets is of greatest importance with regard to the anticancer effects of this agent. The evidence to date is not conclusive, but suggests that the effects of LY293111 may be mediated by both LTB4 receptors and PPAR.

  13. The Leukotriene B4/BLT1 Axis Is a Key Determinant in Susceptibility and Resistance to Histoplasmosis

    Science.gov (United States)

    Secatto, Adriana; Soares, Elyara Maria; Locachevic, Gisele Aparecida; Assis, Patricia Aparecida; Paula-Silva, Francisco Wanderlei Garcia; Serezani, Carlos Henrique; de Medeiros, Alexandra Ivo; Faccioli, Lúcia Helena

    2014-01-01

    The bioactive lipid mediator leukotriene B4 (LTB4) greatly enhances phagocyte antimicrobial functions against a myriad of pathogens. In murine histoplasmosis, inhibition of the LT-generating enzyme 5-lypoxigenase (5-LO) increases the susceptibility of the host to infection. In this study, we investigated whether murine resistance or susceptibility to Histoplasma capsulatum infection is associated with leukotriene production and an enhancement of in vivo and/or in vitro antimicrobial effector function. We show that susceptible C57BL/6 mice exhibit a higher fungal burden in the lung and spleen, increased mortality, lower expression levels of 5-LO and leukotriene B4 receptor 1 (BLT1) and decreased LTB4 production compared to the resistant 129/Sv mice. Moreover, we demonstrate that endogenous and exogenous LTs are required for the optimal phagocytosis of H. capsulatum by macrophages from both murine strains, although C57BL/6 macrophages are more sensitive to the effects of LTB4 than 129/Sv macrophages. Therefore, our results provide novel evidence that LTB4 production and BLT1 signaling are required for a histoplasmosis-resistant phenotype. PMID:24465479

  14. Cysteinyl leukotriene E4 activates human group 2 innate lymphoid cells and enhances the effect of prostaglandin D2 and epithelial cytokines.

    Science.gov (United States)

    Salimi, Maryam; Stöger, Linda; Liu, Wei; Go, Simei; Pavord, Ian; Klenerman, Paul; Ogg, Graham; Xue, Luzheng

    2017-10-01

    Group 2 innate lymphoid cells (ILC2s) are a potential innate source of type 2 cytokines in the pathogenesis of allergic conditions. Epithelial cytokines (IL-33, IL-25, and thymic stromal lymphopoietin [TSLP]) and mast cell mediators (prostaglandin D 2 [PGD 2 ]) are critical activators of ILC2s. Cysteinyl leukotrienes (cysLTs), including leukotriene (LT) C 4 , LTD 4 , and LTE 4 , are metabolites of arachidonic acid and mediate inflammatory responses. Their role in human ILC2s is still poorly understood. We sought to determine the role of cysLTs and their relationship with other ILC2 stimulators in the activation of human ILC2s. For ex vivo studies, fresh blood from patients with atopic dermatitis and healthy control subjects was analyzed with flow cytometry. For in vitro studies, ILC2s were isolated and cultured. The effects of cysLTs, PGD 2 , IL-33, IL-25, TSLP, and IL-2 alone or in combination on ILC2s were defined by using chemotaxis, apoptosis, ELISA, Luminex, quantitative RT-PCR, and flow cytometric assays. The effect of endogenous cysLTs was assessed by using human mast cell supernatants. Human ILC2s expressed the LT receptor CysLT 1 , levels of which were increased in atopic subjects. CysLTs, particularly LTE 4 , induced migration, reduced apoptosis, and promoted cytokine production in human ILC2s in vitro. LTE 4 enhanced the effect of PGD 2 , IL-25, IL-33, and TSLP, resulting in increased production of type 2 and other proinflammatory cytokines. The effect of LTE 4 was inhibited by montelukast, a CysLT 1 antagonist. Interestingly, addition of IL-2 to LTE 4 and epithelial cytokines significantly amplified ILC2 activation and upregulated expression of the receptors for IL-33 and IL-25. CysLTs, particularly LTE 4 , are important contributors to the triggering of human ILC2s in inflammatory responses, particularly when combined with other ILC2 activators. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Effects of drugs inhibiting prostaglandin or leukotriene biosynthesis on postirradiation haematopoiesis in mouse

    International Nuclear Information System (INIS)

    Kozubik, A.; Hofmanova, J.; Pospisil, M.; Netikova, J.; Hola, J.; Lojek, A.

    1994-01-01

    Two non-steroidal anti-inflammatory drugs, i.e. indomethacin (INDO), an inhibitor of prostaglandin production, and esculetin (ESCUL), an inhibitor of leukotriene production, were tested for their ability to modify haematopoiesis in three experimental systems: (a) in vitro clonal proliferation of marrow GM-CFC from the irradiated mouse was found to be augmented by addition of INDO at a low concentration, and inhibited by ESCUL in a dose-dependent manner; (b) in the lethally irradiated and bone marrow-transplanted mice treated with the drugs in the postirradiation period, stimulatory effects of INDO on CFU-S and GM-CFC populations and an inhibitory effect of ESCUL on GM-CFC were observed; and (c) when the drugs were administered i.p. to mice 1 h before 5-Gy irradiation, INDO enhanced the postirradiation recovery of haematopoietic indices such the numbers of CFU-S, GM-CFC, peripheral blood granuloctyes, and nucleated bone marrow cells, while ESCUL had no effect or even inhibited the recovery of these indices. (author)

  16. Population-based open-label clinical effectiveness assessment of the cysteinyl leukotriene receptor antagonist pranlukast

    Directory of Open Access Journals (Sweden)

    Gen Tamura

    2000-01-01

    Full Text Available Although the efficacy of cysteinyl leukotriene receptor antagonists in asthma therapy has been established through controlled clinical trials, there are no data concerning the effectiveness of their use in clinical practice, in which there is no rigid selection based on specific inclusion and exclusion criteria. The aim of the present study was to evaluate the effectiveness of pranlukast in clinical practice. More than 2500 outpatients with mild to severe persistent asthma answered an input questionnaire, which consisted of 33 items assessing asthma symptoms in terms of six activities of daily living during the previous 2 weeks. Of these patients, 1138 received treatment with pranlukast and answered the same questionnaire 4–6 weeks after the start of treatment. In 923 of these 1138 patients, we examined the impact of concomitantly used inhaled steroids, β2-adrenergic agonists or sustained-release theophylline on the effectiveness of pranlukast treatment. One hundred and sixty-seven control patients completed the questionnaire twice but did not receive pranlukast treatment. We found a significant decrease in the number of asthma symptoms reported among both the 1138 patients treated with pranlukast and the 167 control patients. However, the magnitude of the decrease in symptoms was significantly (P < 0.001 greater with pranlukast treatment. Moreover, pranlukast was equally efficacious in the presence and absence of concomitantly used inhaled steroids, β2-adrenergic agonists or sustained-release theophylline. In conclusion, pranlukast was shown to have clinical effectiveness in the treatment of mild to severe persistent asthma symptoms.

  17. Leukotriene formation by purified 5-lipoxygenase from rat basophilic leukemia cells

    International Nuclear Information System (INIS)

    Hogaboom, G.K.; Cook, M.; Sarau, H.M.; Newton, J.F.; Crooke, S.T.

    1986-01-01

    Arachidonate 5-lipoxygenase (5-LO) from rat basophilic leukemia (RBL-1) cell high speed (105,000 x g for 60 min) supernatants was purified to electrophoretic homogeneity by gel filtration and anion-exchange protein-high pressure liquid chromatography (HPLC). The 5-LO rapidly converted [ 14 C]arachidonate at 20 0 C to [ 14 C]5-hydroperoxyeicosate-traenoic acid (HPETE) as determined by reversed phase-HPLC, scanning spectrophotometry and radiochemical detection. In addition, 5-LO converted both 5-HPETE and arachidonate to 5,12-dihydroxyeicosatetraenoic acids (diHETEs). The 5,12-diHETEs were identified as 6-trans-leukotriene (LT) B4 and 6-trans-12-epi-LTB4 as determined by reversed phase HPLC, scanning spectrophotometry and gas chromatography-mass spectrometry. These data indicate that the RBL-1 5-LO and LTA4 synthetase activities reside on the same protein and that it catalyzes the bioconversion of arachidonate to not only 5-HPETE but also to LTA4. The results suggest that a critical regulatory step in LT biosynthesis in mammalian systems involves the intricate coupling of the enzymes 5-LO and LTA4 synthetase and the interactions of their respective cofactors, substrates and reaction products

  18. Characterization of arachidonate 5-lipoxygenase and leukotriene A4 synthetase from RBL-1 cells

    International Nuclear Information System (INIS)

    Cook, M.; Hogaboom, G.K.; Sarau, H.M.; Foley, J.J.; Crooke, S.T.

    1986-01-01

    5-lipoxygenase (LO) and leukotriene (LT) A4 synthetase from RBL-1 high speed (105,000 x g for 60 min) supernatants were partially purified by protein-high performance liquid chromatography (HPLC) and characterized in detail. The partially purified preparation contained only 5-LO and LTA4 synthetase and was isolated from 12-LO, peroxidase and LTA4 hydrolase activities. Reaction products were separated by reversed phase HPLC and quantitated by absorption spectrophotometry and radiochemical detection. The enzyme preparation rapidly converted [ 14 C]arachidonate to [ 14 C]5-hydroperoxyeicosatetraenoic acid (HPETE) and [ 14 C]5,12-dihydroperoxyeicosatetraenoic acids (diHETEs). The 5,12-diHETEs were primarily non-enzymatic breakdown products of LTA4 (e.g., 6-trans-LTB4 and 6-trans-12-epi-LTB4). Both the 5-LO and LTA4 synthetase activities were Ca 2+- and ATP-dependent. For both enzyme activities, the CA 2+ stimulation required the presence of ATP. The fatty acid hydroperoxides, 5-,12-, and 15-HPETE, both stimulated ([ 3 μM]) 5-LO and LTA4 synthetase activities. The rapid isolation and subsequent characterization of 5-LO and LTA4 synthetase provide the bases for the further understanding of the role of the LO pathway in biological processes

  19. Exhaled breath condensate cysteinyl leukotrienes and airway remodeling in childhood asthma: a pilot study

    Directory of Open Access Journals (Sweden)

    Kharitonov Sergei A

    2006-04-01

    Full Text Available Abstract Background It has been suggested that cysteinyl leukotrienes (cysLTs play an important role in airway remodeling. Previous reports have indicated that cysLTs augment human airway smooth muscle cell proliferation. Recently, cysLTs have been measured in exhaled breath condensate (EBC. The aim of this study was to evaluate the relationship between cysLTs in EBC and another marker of airway remodeling, reticular basement membrane (RBM thickening, in endobronchial biopsies in children. Methods 29 children, aged 4–15 years, with moderate to severe persistent asthma, who underwent bronchoscopy as part of their clinical assessment, were included. Subjects underwent spirometry and EBC collection for cysLTs analysis, followed by bronchoscopy and endobronchial biopsy within 24 hours. Results EBC cysLTs were significantly lower in asthmatic children who were treated with montelukast than in those who were not (median (interquartile range 36.62 (22.60–101.05 versus 249.1 (74.21–526.36 pg/ml, p = 0.004. There was a significant relationship between EBC cysLTs and RBM thickness in the subgroup of children who were not treated with montelukast (n = 13, r = 0.75, p = 0.003. Conclusion EBC cysLTs appear to be associated with RBM thickening in asthma.

  20. Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo

    Science.gov (United States)

    Colom, Bartomeu; Bodkin, Jennifer V.; Beyrau, Martina; Woodfin, Abigail; Ody, Christiane; Rourke, Claire; Chavakis, Triantafyllos; Brohi, Karim; Imhof, Beat A.; Nourshargh, Sussan

    2015-01-01

    Summary Breaching endothelial cells (ECs) is a decisive step in the migration of leukocytes from the vascular lumen to the extravascular tissue, but fundamental aspects of this response remain largely unknown. We have previously shown that neutrophils can exhibit abluminal-to-luminal migration through EC junctions within mouse cremasteric venules and that this response is elicited following reduced expression and/or functionality of the EC junctional adhesion molecule-C (JAM-C). Here we demonstrate that the lipid chemoattractant leukotriene B4 (LTB4) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial cell migration (rTEM) in vivo. Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1. The results identify local LTB4-NE axis as a promoter of neutrophil rTEM and provide evidence that this pathway can propagate a local sterile inflammatory response to become systemic. PMID:26047922

  1. Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo.

    Science.gov (United States)

    Colom, Bartomeu; Bodkin, Jennifer V; Beyrau, Martina; Woodfin, Abigail; Ody, Christiane; Rourke, Claire; Chavakis, Triantafyllos; Brohi, Karim; Imhof, Beat A; Nourshargh, Sussan

    2015-06-16

    Breaching endothelial cells (ECs) is a decisive step in the migration of leukocytes from the vascular lumen to the extravascular tissue, but fundamental aspects of this response remain largely unknown. We have previously shown that neutrophils can exhibit abluminal-to-luminal migration through EC junctions within mouse cremasteric venules and that this response is elicited following reduced expression and/or functionality of the EC junctional adhesion molecule-C (JAM-C). Here we demonstrate that the lipid chemoattractant leukotriene B4 (LTB4) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial cell migration (rTEM) in vivo. Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1. The results identify local LTB4-NE axis as a promoter of neutrophil rTEM and provide evidence that this pathway can propagate a local sterile inflammatory response to become systemic. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Leukotriene Receptor Antagonists in the Treatment of Asthma: Implications for Eosinophilic Inflammation

    Directory of Open Access Journals (Sweden)

    Redwan Moqbel

    1999-01-01

    Full Text Available Recent advances in the treatment and management of asthma have suggested that leukotriene (LT receptor antagonists may be very beneficial as a second generation therapy with steroid-sparing properties and negligible side effects. These agents have shown interesting effects on peripheral blood and sputum eosinophils. A major contributor to the damage in the airway of asthmatic patients is the eosinophil, which, upon activation, releases a battery of granule-associated cytotoxic, cationic proteins, including the major basic protein and eosinophil peroxidase, and membrane-derived de novo-synthesized bioactive lipid mediators, including LTC4, LTD4 and LTE4, as well as platelet activating factor. These products have deleterious effects on the airway tissue including mucosal and smooth muscle layers. Accumulating evidence suggests that these agents may also influence the accumulation and maintenance of eosinophilic responses at the site of inflammation. This article reviews the possible anti-inflammatory mode of action of these therapies. It also discusses where there may be a gap in the knowledge regarding the potential direct and indirect effects of LT modifiers on eosinophil function and recruitment.

  3. Effects of drugs inhibiting prostaglandin or leukotriene biosynthesis on postirradiation haematopoiesis in mouse

    Energy Technology Data Exchange (ETDEWEB)

    Kozubik, A.; Hofmanova, J.; Pospisil, M.; Netikova, J.; Hola, J.; Lojek, A. (Ceskoslovenska Akademie Ved, Brno (Czech Republic). Biofysikalni Ustav)

    1994-03-01

    Two non-steroidal anti-inflammatory drugs, i.e. indomethacin (INDO), an inhibitor of prostaglandin production, and esculetin (ESCUL), an inhibitor of leukotriene production, were tested for their ability to modify haematopoiesis in three experimental systems: (a) in vitro clonal proliferation of marrow GM-CFC from the irradiated mouse was found to be augmented by addition of INDO at a low concentration, and inhibited by ESCUL in a dose-dependent manner; (b) in the lethally irradiated and bone marrow-transplanted mice treated with the drugs in the postirradiation period, stimulatory effects of INDO on CFU-S and GM-CFC populations and an inhibitory effect of ESCUL on GM-CFC were observed; and (c) when the drugs were administered i.p. to mice 1 h before 5-Gy irradiation, INDO enhanced the postirradiation recovery of haematopoietic indices such the numbers of CFU-S, GM-CFC, peripheral blood granuloctyes, and nucleated bone marrow cells, while ESCUL had no effect or even inhibited the recovery of these indices. (author).

  4. A study of the photodegradation of leukotriene B4 by ultraviolet irradiation (UVB, UVA)

    International Nuclear Information System (INIS)

    Millar, B.; Green, C.; Ferguson, J.; Raffle, E.J.; Macleod, T.M.

    1989-01-01

    In view of the presence of the polymorphonuclear leukocyte (PMN) chemoattractant Leukotriene B 4 (LTB 4 ) in surface scale of the psoriatic lesion and the known therapeutic effect of phototherapy in psoriasis, the photostability of LTB 4 was investigated. LTB 4 was irradiated with UVB (290-320 nm) from 100-1500 mJ cm -2 and UVA (320-400 nm) from 5-40 J cm -2 . Topical application of UVB irradiated LTB 4 to forearm skin of normal volunteers showed marked reduction in cutaneous erythema, paralleled by reduced transepidermal PMN migration compared with sites of application of unirradiated and UVA irradiated LTB 4 . High performance liquid chromatography (HPLC) demonstrated a dose-dependent photodegradation of LTB 4 by UVB irradiation. UVA irradiation produced no such effect. The wavelengths responsible lie within the absorption spectrum of LTB 4 . In vitro chemotaxis studies, using an under agarose technique, showed a statistically significant reduction in the migration of PMN from psoriatic and non-psoriatic subjects to the UVB irradiated LTB 4 compared with unirradiated LTB 4 , whilst UVA irradiated LTB 4 produced a normal PMN chemotactic response. (author)

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

    Science.gov (United States)

    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

  6. Leukotriene B4 omega-hydroxylase in human polymorphonuclear leukocytes. Suicidal inactivation by acetylenic fatty acids.

    Science.gov (United States)

    Shak, S; Reich, N O; Goldstein, I M; Ortiz de Montellano, P R

    1985-10-25

    Human polymorphonuclear leukocytes (PMN) not only generate and respond to leukotriene B4 (LTB4), but also catabolize this mediator of inflammation rapidly and specifically by omega-oxidation (probably due to the action of a cytochrome P-450 enzyme). To develop pharmacologically useful inhibitors of the LTB4 omega-hydroxylase in human PMN, we devised a general scheme for synthesizing terminal acetylenic fatty acids based on the "acetylenic zipper" reaction. We found that the LTB4 omega-hydroxylase in intact PMN and in PMN sonicates is inactivated in a concentration-dependent fashion by terminal acetylenic analogues of lauric, palmitic, and stearic acids (i.e. 11-dodecynoic, 15-hexadecynoic, and 17-octadecynoic acids). Consistent with a suicidal process, inactivation of the LTB4 omega-hydroxylase requires molecular oxygen and NADPH, is time-dependent, and follows pseudo-first-order kinetics. Inactivation of the omega-hydroxylase by acetylenic fatty acids also is dependent on the terminal acetylenic moiety and the carbon chain length. Saturated fatty acids lacking a terminal acetylenic moiety do not inactivate the omega-hydroxylase. In addition, the two long-chain (C16, C18) acetylenic fatty acids inactivate the omega-hydroxylase at much lower concentrations (less than 5.0 microM) than those required for inactivation by the short-chain (C12) terminal acetylenic fatty acid (100 microM). Potent suicidal inhibitors of the LTB4 omega-hydroxylase in human PMN will help elucidate the roles played by LTB4 and its omega-oxidation products in regulating PMN function and in mediating inflammation.

  7. Increase in salivary cysteinyl-leukotriene concentration in patients with aspirin-intolerant asthma.

    Science.gov (United States)

    Ono, Emiko; Taniguchi, Masami; Higashi, Noritaka; Mita, Haruhisa; Yamaguchi, Hiromichi; Tatsuno, Sayaka; Fukutomi, Yuma; Tanimoto, Hidenori; Sekiya, Kiyoshi; Oshikata, Chiyako; Tsuburai, Takahiro; Tsurikisawa, Naomi; Otomo, Mamoru; Maeda, Yuji; Hasegawa, Maki; Miyazaki, Eishi; Kumamoto, Toshihide; Akiyama, Kazuo

    2011-03-01

    Cysteinyl-leukotrienes (CysLTs; LTC4, LTD4, and LTE4) play a considerable role in the pathophysiology of aspirin-intolerant asthma (AIA). Saliva has recently been validated as novel, simple, and noninvasive method for investigating inflammation in patients with asthma. The aim of this study is to clarify the molecular species of CysLT in saliva and to evaluate the CysLT and LTB4 concentrations in saliva in AIA patients. We also examined how the CysLT concentration in saliva reflects that of their corresponding urinary metabolite. We preformed an analytical cross-sectional study. CysLT and LTB4 concentrations in saliva were quantified by enzyme immunoassay (EIA) following purification by high-performance liquid chromatography (HPLC). 1. When analyzed by EIA in combination with HPLC, saliva was found to consist of LTC4, LTD4 and LTE4 in similar amounts. 2. In saliva analysis among the three groups (AIA patients, aspirin-tolerant asthma [ATA] patients, and healthy subjects), both the concentrations of CysLTs and LTB4 were significantly higher in AIA patients than in ATA patients and healthy subjects. 3. We found significant correlations between CysLT concentration and LTB4 concentration in saliva in each group. 4. No significant correlation was found between the concentration of LTE4 in urine and that of CysLTs in saliva. In this study, we found higher concentrations of CysLTs and LTB4 in saliva from AIA patients than in saliva from ATA patients, suggesting that the quantification of CysLT and LTB4 concentrations in saliva may be another diagnostic strategy for AIA.

  8. Liquid chromatography/mass spectrometry analysis of exhaled leukotriene B4 in asthmatic children

    Directory of Open Access Journals (Sweden)

    Barnes Peter J

    2005-10-01

    Full Text Available Abstract Background The role of leukotriene (LT B4, a potent inflammatory mediator, in atopic asthmatic and atopic nonasthmatic children is largely unknown. The lack of a gold standard technique for measuring LTB4 in exhaled breath condensate (EBC has hampered its quantitative assessment in this biological fluid. We sought to measure LTB4 in EBC in atopic asthmatic children and atopic nonasthmatic children. Exhaled nitric oxide (NO was measured as an independent marker of airway inflammation. Methods Fifteen healthy children, 20 atopic nonasthmatic children, 25 steroid-naïve atopic asthmatic children, and 22 atopic asthmatic children receiving inhaled corticosteroids were studied. The study design was of cross-sectional type. Exhaled LTB4 concentrations were measured using liquid chromatography/mass spectrometry-mass spectrometry (LC/MS/MS with a triple quadrupole mass spectrometer. Exhaled NO was measured by chemiluminescence with a single breath on-line method. LTB4 values were expressed as the total amount (in pg of eicosanoid expired in the 15-minute breath test. Kruskal-Wallis test was used to compare groups. Results Compared with healthy children [87.5 (82.5–102.5 pg, median and interquartile range], exhaled LTB4 was increased in steroid-naïve atopic asthmatic [255.1 (175.0–314.7 pg, p 4 than steroid-naïve asthmatics [125.0 (25.0–245.0 pg vs 255.1 (175.0–314.7 pg, p Conclusion In contrast to exhaled NO concentrations, exhaled LTB4 values are selectively elevated in steroid-naïve atopic asthmatic children, but not in atopic nonasthmatic children. Although placebo control studies are warranted, inhaled corticosteroids seem to reduce exhaled LTB4 in asthmatic children. LC/MS/MS analysis of exhaled LTB4 might provide a non-invasive, sensitive, and quantitative method for airway inflammation assessment in asthmatic children.

  9. Metabolism of leukotriene B4 to dihydro and dihydro-oxo products by porcine leukocytes

    International Nuclear Information System (INIS)

    Powell, W.S.; Gravelle, F.

    1989-01-01

    Porcine leukocytes contain a novel pathway for the metabolism of leukotriene B4 (LTB4) which results in reduction of the conjugated triene chromophore to a conjugated diene. These cells converted LTB4 to two major metabolites, both of which exhibited maximal absorbance at 230 nm in their UV spectra. These products were purified by high pressure liquid chromatography and identified as 10, 11-dihydro-LTB4 and 10,11-dihydro-12-oxo-LTB4 on the basis of the mass spectra of various derivatives. The position of the double bond of LTB4 which had been reduced was established by cleaving the remaining double bonds of 10, 11-dihydro-LTB4 with ozone followed by oxidation or reduction of the resulting ozonide and analysis of the products by mass spectrometry. Experiments with deuterium-labeled substrate indicated that LTB4 could be directly converted to 10, 11-dihydro-LTB4 without the prior oxidation of either of its hydroxyl groups, as is required for the formation of dihydro metabolites of prostaglandins. Incubation of porcine leukocytes with 10, 11-dihydro-LTB4 and 10, 11-dihydro-12-oxo-LTB4 indicated that these two products can be interconverted and are in equilibrium with one another. The dihydro-oxo metabolite can therefore be formed from 10, 11-dihydro-LTB4, although we have not ruled out the possibility that it is also produced via 12-oxo-LTB4, which could be a transitory intermediate. These results indicate that porcine leukocytes contain a novel reductase/dehydrogenase pathway distinct from the pathway responsible for the metabolism of prostaglandins. This pathway is also different from the pathway in human polymorphonuclear leukocytes which converts 6-trans-isomers of LTB4 to dihydro products, since the latter pathway involves 5-oxo intermediates and results in a shift in the positions of the remaining double bonds

  10. Identification of a murine cysteinyl leukotriene receptor by expression in Xenopus laevis oocytes

    DEFF Research Database (Denmark)

    Mollerup, Jens; Jørgensen, Sune T.; Hougaard, Charlotte

    2001-01-01

    We report the identification of an EST encoding a murine cysteinyl leukotriene (mCysLT) receptor. LTD4, LTC4 and LTE4 but not LTB4 or various nucleotides activated Ca2+-evoked Cl- currents in mCysLT1 expressing Xenopus laevis oocytes. The response to LTD4 was blocked by MK-571, reduced by pretrea...... by pretreatment with pertussis toxin (PTX), and was partly dependent on extracellular Ca2+. The identified murine CysLT1 receptor differs from the hCysLT1 receptor with regard to PTX sensitivity, receptor-mediated Ca2+ influx, and antagonist sensitivity....

  11. Leukotriene signaling in the extinct human subspecies Homo denisovan and Homo neanderthalensis. Structural and functional comparison with Homo sapiens.

    Science.gov (United States)

    Adel, Susan; Kakularam, Kumar Reddy; Horn, Thomas; Reddanna, Pallu; Kuhn, Hartmut; Heydeck, Dagmar

    2015-01-01

    Mammalian lipoxygenases (LOXs) have been implicated in cell differentiation and in the biosynthesis of pro- and anti-inflammatory lipid mediators. The initial draft sequence of the Homo neanderthalensis genome (coverage of 1.3-fold) suggested defective leukotriene signaling in this archaic human subspecies since expression of essential proteins appeared to be corrupted. Meanwhile high quality genomic sequence data became available for two extinct human subspecies (H. neanderthalensis, Homo denisovan) and completion of the human 1000 genome project provided a comprehensive database characterizing the genetic variability of the human genome. For this study we extracted the nucleotide sequences of selected eicosanoid relevant genes (ALOX5, ALOX15, ALOX12, ALOX15B, ALOX12B, ALOXE3, COX1, COX2, LTA4H, LTC4S, ALOX5AP, CYSLTR1, CYSLTR2, BLTR1, BLTR2) from the corresponding databases. Comparison of the deduced amino acid sequences in connection with site-directed mutagenesis studies and structural modeling suggested that the major enzymes and receptors of leukotriene signaling as well as the two cyclooxygenase isoforms were fully functional in these two extinct human subspecies. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Urinary Leukotriene E4 Is Associated with Renal Function but Not with Endothelial Function in Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Arnar Rafnsson

    2013-01-01

    Full Text Available Leukotrienes are inflammatory and vasoactive mediators implicated in endothelium-dependent relaxations and atherosclerosis. Urinary leukotriene E4 (U-LTE4 is a validated disease marker of asthma and increases also in diabetes and acute coronary syndromes. The aim of the present study was to evaluate the association of U-LTE4 and CRP with endothelial function. Urine samples were obtained from 30 subjects (80% males; median age 65 with type 2 diabetes of at least two years duration and a median glomerular filtration rate (eGFR of 71 (14–129 mL/min. Reactive hyperemia index (RHI was used as a measure of microvascular endothelial function, whereas macrovascular endothelial function was determined be means of flow-mediated dilatation of the brachial artery (FMD. Decreased renal function was associated with lower concentrations of U-LTE4. In addition, U-LTE4 was correlated with serum creatinine (R=−0.572; P=0.001 and eGFR (R=0.517; P=0.0036. A stepwise multiple linear regression analysis identified eGFR as an independent predictor of U-LTE4 concentrations. In conclusion, the present results did not establish an association of U-LTE4 with endothelial dysfunction. However, eGFR was an independent predictor of U-LTE4, but not CRP, in this cohort, suggesting that GFR should be considered in biomarker studies of U-LTE4.

  13. Effect of leukotriene receptor antagonists on vascular permeability during endotoxic shock

    International Nuclear Information System (INIS)

    Cook, J.A.; Li, E.J.; Spicer, K.M.; Wise, W.C.; Halushka, P.V.

    1990-01-01

    Evidence has accumulated that sulfidopeptide leukotrienes are significant pathogenic mediators of certain hematologic and hemodynamic sequelae of endotoxic shock. In the present study, the effects of a selective LTD4/E4 receptor antagonist, LY171883 (LY), or a selective LTD4 receptor antagonist, SKF-104353 (SKF), were assessed on splanchnic and pulmonary localization of 99mTechnetium-labeled human serum albumin (99mTc-HSA) in acute endotoxic shock in the rat. Dynamic gamma camera imaging of heart (H), midabdominal (GI), and lung regions of interest generated time activity curves for baseline and at 5-35 min after Salmonella enteritidis endotoxin (10 mg/kg, i.v.). Slopes of GI/H and lung/H activity (permeability index, GI/H or lung/H X 10(-3)/min) provided indices of intestinal and lung localization. Rats received LY (30 mg/kg, i.v.), LY vehicle (LY Veh), SKF (10 mg/kg), or SKF vehicle (SK Veh) 10 min prior to endotoxin or endotoxin vehicle. In rats receiving the LY Veh and endotoxin (n = 8) or SKF Veh and endotoxin (n = 12), the splanchnic permeability indices to 99mTc-HSA were increased 11.2-fold and 5.1-fold, respectively (P less than 0.05) compared to vehicle control groups not given endotoxin (n = 5). Pulmonary permeability index for 99mTc-HSA was increased (P less than 0.05) to a lesser extent (3.2-fold) by endotoxin compared to vehicle controls. Pretreatment with SKF reduced the mesenteric permeability index to control levels (P less than 0.05) during the 5-35 min time interval post-endotoxin. LY reduced the mesenteric permeability index by 70%. Pulmonary relative permeability to 99mTc-HSA was not affected by LY pretreatment. Both splanchnic and lung relative permeability to the isotope was transient; at 135-225 min post-endotoxin, splanchnic localization of 99mTc-HSA (n = 4) was not significantly different from vehicle controls in these vascular beds

  14. A geranyl acetophenone targeting cysteinyl leukotriene synthesis prevents allergic airway inflammation in ovalbumin-sensitized mice

    International Nuclear Information System (INIS)

    Ismail, Norazren; Jambari, Nuzul Nurahya; Zareen, Seema; Akhtar, Mohamad Nadeem; Shaari, Khozirah; Zamri-Saad, Mohamad; Tham, Chau Ling; Sulaiman, Mohd Roslan; Lajis, Nordin Hj; Israf, Daud Ahmad

    2012-01-01

    Asthma is associated with increased pulmonary inflammation and airway hyperresponsiveness. The current use of corticosteroids in the management of asthma has recently raised issues regarding safety and lack of responsiveness in 5–10% of asthmatic individuals. The aim of the present study was to investigate the therapeutic effect of a non-steroidal small molecule that has cysteinyl leukotriene (cysLT) inhibitory activity, upon attenuation of allergic lung inflammation in an acute murine model. Mice were sensitized with ovalbumin (OVA) and treated with several intraperitoneal doses (100, 20, 2 and 0.2 mg/kg) of 2,4,6,-trihydroxy-3-geranylacetophenone (tHGA). Bronchoalveolar lavage was performed, blood and lung samples were obtained and respiratory function was measured. OVA sensitization increased pulmonary inflammation and pulmonary allergic inflammation was significantly reduced at doses of 100, 20 and 2 mg/kg with no effect at the lowest dose of 0.2 mg/kg. The beneficial effects in the lung were associated with reduced eosinophilic infiltration and reduced secretion of Th2 cytokines and cysLTs. Peripheral blood reduction of total IgE was also a prominent feature. Treatment with tHGA significantly attenuated altered airway hyperresponsiveness as measured by the enhanced pause (Penh) response to incremental doses of methacholine. These data demonstrate that tHGA, a synthetic non-steroidal small molecule, can prevent acute allergic inflammation. This proof of concept opens further avenues of research and development of tHGA as an additional option to the current armamentarium of anti-asthma therapeutics. -- Highlights: ► Safer and effective anti-asthmatic drugs are in great demand. ► tHGA is a new 5-LO/cysLT inhibitor that inhibits allergic asthma in mice. ► tHGA is a natural compound that can be synthesized. ► Doses as low as 2 mg/kg alleviate lung pathology in experimental asthma. ► tHGA is a potential drug lead for the treatment of allergic asthma.

  15. Modulation of the heterogeneous membrane potential response of neutrophils to N-formyl-methionyl-leucyl-phenylalanine (FMLP) by leukotriene B4: evidence for cell recruitment

    International Nuclear Information System (INIS)

    Fletcher, M.P.

    1986-01-01

    Individual human neutrophils (PMN) isolated by Hypaque-Ficoll gradient sedimentation, dextran sedimentation, or buffy coat preparation were assessed for the effects of leukotriene B4 (5S,12R dihydroxy 6,14-cis-8, 10 trans eicosatetraenoic acid (LTB4)-pretreatment on N-formylmethionyl-leucyl-phenylalanine (FMLP)-mediated membrane potential or oxidative responses by using flow cytometry and a lipophilic probe of membrane potential (di-pentyl-oxacarbocyanine, di-O-C(5)3), or the nitroblue tetrazolium dye (NBT) reduction test, respectively. Although exposure to LTB4 (10(-7) M) had no effect on the membrane potential of resting PMN and little effect on oxidant production, pretreating PMN with LTB4 followed by FMLP (10(-6) M) demonstrated a significant enhancement in the proportion of depolarizing PMN over that seen with FMLP alone (p = 0.0014, N = 9). This recruitment of previously unresponsive cells by LTB4 was dose and time dependent, with the maximal relative increase in the proportion of depolarizing cells occurring at LTB4 concentrations of 10(-8) to 10(-7) M and within 1 min of LTB4 addition. The recruitment effect persisted despite vigorous washing of the cells. LTB4 also increased the proportion of NBT-positive PMN in response to FMLP. Although LTB4 alone did not depolarize PMN it did induce a light scatter shift indicative of cell activation. 3 H-FMLP binding studied at 0 degree C comparing buffer and LTB4-treated PMN indicated no significant change in the number or affinity of FMLP binding. The data provide evidence for the recruitment of a greater proportion of cells into a FMLP-responsive state as a mechanism for the enhanced functional response of PMN pretreated with LTB4, as well as for a dissociation of the membrane potential and light scattering responses of cells to this pro-inflammatory LT

  16. 2016 updated MASCC/ESMO consensus recommendations : Prevention of acute chemotherapy-induced nausea and vomiting in children

    NARCIS (Netherlands)

    Dupuis, L. Lee; Sung, Lillian; Molassiotis, Alexander; Orsey, Andrea D.; Tissing, Wim; van de Wetering, Marianne

    To update the 2009 recommendations for the prevention of acute chemotherapy-induced emesis in children. We updated the original systematic literature search. Randomized studies were included in the evidence to support this guideline if they were primary studies fully published in full text in

  17. Determination of thromboxanes, leukotrienes and lipoxins using high-temperature capillary liquid chromatography-tandem mass spectrometry and on-line sample preparation

    DEFF Research Database (Denmark)

    Dahl, Sandra Rinne; Kleiveland, Charlotte Ramstad; Kassem, Moustapha

    2009-01-01

    An on-line strong cation-exchange (SCX)-reversed-phase (RP) capillary liquid chromatographic (cLC) method with ion-trap tandem mass spectrometric (IT-MS/MS) detection for the simultaneous determination of thromboxane (TX) B(2), TXB(3), leukotriene (LT) B(4), LTD(4) and lipoxin (LX) A(4) in cell...

  18. Endogenous secreted phospholipase A2 group X regulates cysteinyl leukotrienes synthesis by human eosinophils.

    Science.gov (United States)

    Hallstrand, Teal S; Lai, Ying; Hooper, Kathryn A; Oslund, Rob C; Altemeier, William A; Matute-Bello, Gustavo; Gelb, Michael H

    2016-01-01

    Phospholipase A2s mediate the rate-limiting step in the formation of eicosanoids such as cysteinyl leukotrienes (CysLTs). Group IVA cytosolic PLA2α (cPLA2α) is thought to be the dominant PLA2 in eosinophils; however, eosinophils also have secreted PLA2 (sPLA2) activity that has not been fully defined. To examine the expression of sPLA2 group X (sPLA2-X) in eosinophils, the participation of sPLA2-X in the formation of CysLTs, and the mechanism by which sPLA2-X initiates the synthesis of CysLTs in eosinophils. Peripheral blood eosinophils were obtained from volunteers with asthma and/or allergy. A rabbit polyclonal anti-sPLA2-X antibody identified sPLA2-X by Western blot. We used confocal microscopy to colocalize the sPLA2-X to intracellular structures. An inhibitor of sPLA2-X (ROC-0929) that does not inhibit other mammalian sPLA2s, as well as inhibitors of the mitogen-activated kinase cascade (MAPK) and cPLA2α, was used to examine the mechanism of N-formyl-methionyl-leucyl-phenylalanine (fMLP)-mediated formation of CysLT. Eosinophils express the mammalian sPLA2-X gene (PLA2G10). The sPLA2-X protein is located in the endoplasmic reticulum, golgi, and granules of eosinophils and moves to the granules and lipid bodies during fMLP-mediated activation. Selective sPLA2-X inhibition attenuated the fMLP-mediated release of arachidonic acid and CysLT formation by eosinophils. Inhibitors of p38, extracellular-signal-regulated kinases 1/2 (p44/42 MAPK), c-Jun N-terminal kinase, and cPLA2α also attenuated the fMLP-mediated formation of CysLT. The sPLA2-X inhibitor reduced the phosphorylation of p38 and extracellular-signal-regulated kinases 1/2 (p44/42 MAPK) as well as cPLA2α during cellular activation, indicating that sPLA2-X is involved in activating the MAPK cascade leading to the formation of CysLT via cPLA2α. We further demonstrate that sPLA2-X is activated before secretion from the cell during activation. Short-term priming with IL-13 and TNF/IL-1β increased the

  19. A new practical method for the preparation of [3H6]-leukotrienes C4 and D4

    International Nuclear Information System (INIS)

    Belley, M.L.; Gareau, Y.; Zamboni, R.J.; Ahern, D.G.; Yang Hong

    1995-01-01

    A new method for the synthesis of highly deuterated or tritiated leukotrienes was developed. The higher reactivity of a terminal alkene compared to a 1,2-disubstituted one permitted the selective deuteration or tritiation of the diyne 14,15,19,19,20,20-hexadehydro LTC 4 troester 1. After hydrolysis, LTC 4 was obtained in 36% overall yield. An average of seven deuterium or tritium atoms was incorporated and the specific activity of the tritiated LTC 4 was greater than 180Ci/mmol. 1 was obtained from the addition of glutathione to 14,15,19,19,20,20-hexadehydro LTA 4 ethyl ester which was the product of a Wittig reaction between (3,8-nonanediyn-1-yl) triphenylphosphonium iodide and 5(S), 6(S), 7(E), 9(E) ethyl 5,6-epoxy-11-oxo-7,9-undecadienoate. (Author)

  20. Omega-oxidation is the major pathway for the catabolism of leukotriene B4 in human polymorphonuclear leukocytes.

    Science.gov (United States)

    Shak, S; Goldstein, I M

    1984-08-25

    Leukotriene B4 (LTB4), formed by the 5-lipoxygenase pathway in human polymorphonuclear leukocytes (PMN), may be an important mediator of inflammation. Recent studies suggest that human leukocytes can convert LTB4 to products that are less biologically active. To examine the catabolism of LTB4, we developed (using high performance liquid chromatography) a sensitive, reproducible assay for this mediator and its omega-oxidation products (20-OH- and 20-COOH-LTB4). With this assay, we have found that human PMN (but not human monocytes, lymphocytes, or platelets) convert exogenous LTB4 almost exclusively to 20-OH- and 20-COOH-LTB4 (identified by gas chromatography-mass spectrometry). Catabolism of exogenous LTB4 by omega-oxidation is rapid (t1/2 approximately 4 min at 37 degrees C in reaction mixtures containing 1.0 microM LTB4 and 20 X 10(6) PMN/ml), temperature-dependent (negligible at 0 degrees C), and varies with cell number as well as with initial substrate concentration. The pathway for omega-oxidation in PMN is specific for LTB4 and 5(S),12(S)-dihydroxy-6,8,10,14-eicosatetraenoic acid (only small amounts of other dihydroxylated-derivatives of arachidonic acid are converted to omega-oxidation products). Even PMN that are stimulated by phorbol myristate acetate to produce large amounts of superoxide anion radicals catabolize exogenous leukotriene B4 primarily by omega-oxidation. Finally, LTB4 that is generated when PMN are stimulated with the calcium ionophore, A23187, is rapidly catabolized by omega-oxidation. Thus, human PMN not only generate and respond to LTB4, but also rapidly and specifically catabolize this mediator by omega-oxidation.

  1. Effect of montelukast on platelet activating factor- and tachykinin induced mucus secretion in the rat

    Directory of Open Access Journals (Sweden)

    Groneberg David A

    2008-02-01

    Full Text Available Abstract Background Platelet activating factor and tachykinins (substance P, neurokinin A, neurokinin B are important mediators contributing to increased airway secretion in the context of different types of respiratory diseases including acute and chronic asthma. Leukotriene receptor antagonists are recommended as add-on therapy for this disease. The cys-leukotriene-1 receptor antagonist montelukast has been used in clinical asthma therapy during the last years. Besides its inhibitory action on bronchoconstriction, only little is known about its effects on airway secretions. Therefore, the aim of this study was to evaluate the effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity. Methods The effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity in the rat were assessed by quantification of secreted 35SO4 labelled mucus macromolecules using the modified Ussing chamber technique. Results Platelet activating factor potently stimulated airway secretion, which was completely inhibited by the platelet activating factor receptor antagonist WEB 2086 and montelukast. In contrast, montelukast had no effect on tachykinin induced tracheal secretory activity. Conclusion Cys-leukotriene-1 receptor antagonism by montelukast reverses the secretagogue properties of platelet activating factor to the same degree as the specific platelet activating factor antagonist WEB 2086 but has no influence on treacheal secretion elicited by tachykinins. These results suggest a role of montelukast in the signal transduction pathway of platelet activating factor induced secretory activity of the airways and may further explain the beneficial properties of cys-leukotriene-1 receptor antagonists.

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

    Science.gov (United States)

    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.

  3. Selective blockade of leukotriene production by a single dose of the FPL 64170XX 0.5% enema in active ulcerative colitis

    DEFF Research Database (Denmark)

    Kjeldsen, J; Laursen, L S; Hillingsø, Jens

    1995-01-01

    5-Lipoxygenase products of arachidonic acid metabolism are thought to play a central role in the secondary amplification of the inflammatory response of several inflammatory diseases, including ulcerative colitis. FPL 64170XX is a selective inhibitor of the enzyme 5-lipoxygenase. Concentrations...... containing 0.5% of FPL 64170XX. Repeated measures analysis of leukotriene B4, after adjusting for baseline, showed a significant treatment effect (P = 0.0014). The concentration of leukotriene B4 from rectal dialysates in patients receiving the active drug dropped to 15% (95% confidence interval 5......-40%) of the placebo level in the second dialysis following administration of FPL 64170XX 0.5%. By contrast, prostaglanding E2 concentrations doubled (P = 0.0068) in patients receiving FPL 64170XX 0.5% with no change in the placebo group. These findings demonstrate that a single dose of FPL 64170XX 0.5% enema...

  4. The leukotriene B{sub 4} receptor, BLT1, is required for the induction of experimental autoimmune encephalomyelitis

    Energy Technology Data Exchange (ETDEWEB)

    Kihara, Yasuyuki, E-mail: kihara-yasuyuki@umin.net [Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Yokomizo, Takehiko [Department of Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 (Japan); Core Research for Embryonic Science and Technology (CREST), Japan Science and Technology Agency (Japan); Kunita, Akiko; Morishita, Yasuyuki; Fukayama, Masashi [Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033 (Japan); Ishii, Satoshi; Shimizu, Takao [Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

    2010-04-09

    Leukotriene B{sub 4} (LTB{sub 4}) is a potent chemoattractant and activator of neutrophils, macrophages and T cells. These cells are a key component of inflammation and all express BLT1, a high affinity G-protein-coupled receptor for LTB{sub 4}. However, little is known about the neuroimmune functions of BLT1. In this study, we describe a distinct role for BLT1 in the pathology of experimental autoimmune encephalomyelitis (EAE) and T{sub H}1/T{sub H}17 immune responses. BLT1 mRNA was highly upregulated in the spinal cord of EAE mice, especially during the induction phase. BLT1{sup -/-} mice had delayed onset and less severe symptoms of EAE than BLT1{sup +/+} mice. Additionally, inflammatory cells were recruited to the spinal cord of asymptomatic BLT1{sup +/+}, but not BLT1{sup -/-} mice before the onset of disease. Ex vivo studies showed that both the proliferation and the production of IFN-{gamma}, TNF-{alpha}, IL-17 and IL-6 were impaired in BLT1{sup -/-} cells, as compared with BLT1{sup +/+} cells. Thus, we suggest that BLT1 exacerbates EAE by regulating the migration of inflammatory cells and T{sub H}1/T{sub H}17 immune responses. Our findings provide a novel therapeutic option for the treatment of multiple sclerosis and other T{sub H}17-mediated diseases.

  5. Hypercholesterolemia Increases the Production of Leukotriene B4 in Neutrophils by Enhancing the Nuclear Localization of 5-Lipoxygenase

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    Xiao-Feng Lai

    2014-11-01

    Full Text Available Aims: Neutrophils can synthesize leukotriene B4 (LTB4 by activating the 5-lipoxygenase (5-LOsignaling pathway. LTB4 is a pro-inflammatory mediator associated with the etiology and progression of atherosclerosis. It can increase function and number of neutrophils in an autocrine manner. Since hypercholesterolemia is associated with an increase in the number and function of neutrophils, we hypothesized that this effect could be mediated through increased production of LTB4 in neutrophils. Methods/Results: Hypercholesterolemia was modeled in Wistar rats by feeding them with a high cholesterol diet. The induction of hypercholesterolemia caused an increase in the plasma levels of LTB4, following lipopolysaccharide stimulation. This effect was recapitulated in vitro, both in the presence and absence of stimulation with the activator of 5-LO, A23187. Neutrophils in hypercholesterolemia rats expressed similar total levels of 5-LO as control rats, but displayed increased nuclear localization of 5-LO, as well as elevated levels of phosphorylated 5-LO and ERK1/2. In vitro, MβCD/cholesterol complexes enriched cholesterol in neutrophils, resulted in similar changes in 5-LO/LTB4. In addition, these alterations could be inhibited with the ERK inhibitor PD98059. Conclusion: Hypercholesterolemia increases LTB4 production in neutrophils by increasing the nuclear localization of 5-LO, which is the result of its phosphorylation by activated ERK1/2.

  6. Tissue distribution of a leukotriene antagonist 14C-LY170680, following inhalation exposure in the rat

    International Nuclear Information System (INIS)

    Pohland, R.C.; Beck, J.M.; Carlson, K.H.; Herman, D.R.; Hoppes, J.L.; Vavrek, M.T.; Wolff, R.K.

    1991-01-01

    Dissection and whole-body autoradiographic techniques were used to determine the tissue distribution profile of a leukotriene antagonist, 14 C-LY170680, following nose-only inhalation exposure in the rat. Liquid scintillation spectrometry and whole-body autoradiography indicated that highest concentrations of radiocarbon were present in stomach and small intestine at all time points. Radiocarbon reached maximum levels in stomach (2,259 ng-eq/g) and small intestine (2,399 ng-eq/g) 2 to 4 hours postexposure, respectively, and declined with time. In contrast, maximum radiocarbon concentrations in the head (146 ng-eq/g), trachea (408 ng-eq/g), and lung (534 ng-eq/g) occurred at 0 hours postexposure and steadily declined with time. Low concentrations of radiocarbon were detected in the liver ( 14 C-LY170680 were deposited in the head and within the lung following inhalation exposure. However, higher levels of radiocarbon present in the stomach and small intestine suggested significant nasal deposition followed by rapid clearance and ingestion of inhaled radioactive material. Distribution of radiocarbon limited to the respiratory and gastrointestinal tracts demonstrated minimal systemic absorption and exposure over the time course of this study

  7. Leukotrienes are upregulated and associated with human T-lymphotropic virus type 1 (HTLV-1-associated neuroinflammatory disease.

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    Bruno Caetano Trindade

    Full Text Available Leukotrienes (LTs are lipid mediators involved in several inflammatory disorders. We investigated the LT pathway in human T-lymphotropic virus type 1 (HTLV-1 infection by evaluating LT levels in HTLV-1-infected patients classified according to the clinical status as asymptomatic carriers (HACs and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP patients. Bioactive LTB(4 and CysLTs were both increased in the plasma and in the supernatant of peripheral blood mononuclear cell cultures of HTLV-1-infected when compared to non-infected. Interestingly, CysLT concentrations were increased in HAM/TSP patients. Also, the concentration of plasma LTB(4 and LTC(4 positively correlated with the HTLV-1 proviral load in HTLV-1-infected individuals. The gene expression levels of LT receptors were differentially modulated in CD4(+ and CD8(+ T cells of HTLV-1-infected patients. Analysis of the overall plasma signature of immune mediators demonstrated that LT and chemokine amounts were elevated during HTLV-1 infection. Importantly, in addition to CysLTs, IP-10 was also identified as a biomarker for HAM/TSP activity. These data suggest that LTs are likely to be associated with HTLV-1 infection and HAM/TSP development, suggesting their putative use for clinical monitoring.

  8. Clinical evaluation of leukotriene receptor antagonists in preventing common cold-like symptoms in bronchial asthma patients.

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    Horiguchi, Takahiko; Ohira, Daisuke; Kobayashi, Kashin; Hirose, Masahiro; Miyazaki, Junichi; Kondo, Rieko; Tachikawa, Soichi

    2007-09-01

    We investigated the possibility of preventing common cold-like symptoms as a previously unknown benefit of leukotriene receptor antagonists (LTRAs). A total of 279 adult patients with bronchial asthma referred to our hospital between June and December 2004 were retrospectively analyzed. Patients were divided into LTRA treated and untreated groups. Frequency of acute exacerbations and number of visits to emergency rooms and of hospital admissions were analyzed as indicators of frequency of infections and asthma exacerbation over the previous 12 months. Irrespective of inhaled corticosteroid (ICS) use, frequency of infections was significantly lower in the LTRA treated group (0.3 +/- 0.7 times/year) than in the LTRA untreated group (1.6 +/- 4.2 times/year) (P cold-like symptoms. Frequency of acute exacerbations and number of hospital admissions were significantly lower in the LTRA treated versus LTRA untreated group (0.4 +/- 0.8 versus 2.7 +/- 4.3 times/year and 0.0 +/- 0.2 versus 0.4 +/- 0.7 times/year, respectively; both P cold-like symptoms than those not receiving LTRAs. LTRAs play an important role in reducing the incidence of common cold-like symptoms among asthma patients and in suppressing exacerbation of asthma symptoms possibly associated with these symptoms.

  9. Evidence for eosinophil recruitment, leukotriene B4 production and mast cell hyperplasia following Toxocara canis infection in rats

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    D. Carlos

    2011-04-01

    Full Text Available It is well known that eosinophilia is a key pathogenetic component of toxocariasis. The objective of the present study was to determine if there is an association between peritoneal and blood eosinophil influx, mast cell hyperplasia and leukotriene B4 (LTB4 production after Toxocara canis infection. Oral inoculation of 56-day-old Wistar rats (N = 5-7 per group with 1000 embryonated eggs containing third-stage (L3 T. canis larvae led to a robust accumulation of total leukocytes in blood beginning on day 3 and peaking on day 18, mainly characterized by eosinophils and accompanied by higher serum LTB4 levels. At that time, we also noted increased eosinophil numbers in the peritoneal cavity. In addition, we observed increased peritoneal mast cell number in the peritoneal cavity, which correlated with the time course of eosinophilia during toxocariasis. We also demonstrated that mast cell hyperplasia in the intestines and lungs began soon after the T. canis larvae migrated to these compartments, reaching maximal levels on day 24, which correlated with the complete elimination of the parasite. Therefore, mast cells appear to be involved in peritoneal and blood eosinophil infiltration through an LTB4-dependent mechanism following T. canis infection in rats. Our data also demonstrate a tight association between larval migratory stages and intestinal and pulmonary mast cell hyperplasia in the toxocariasis model.

  10. Cysteinyl leukotrienes C4 and D4 downregulate human mast cell expression of toll-like receptors 1 through 7.

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    Karpov, V; Ilarraza, R; Catalli, A; Kulka, M

    2018-01-01

    Cysteinyl leukotrienes (CysLT) are potent inflammatory lipid molecules that mediate some of the pathophysiological responses associated with asthma such as bronchoconstriction, vasodilation and increased microvascular permeability. As a result, CysLT receptor antagonists (LRA), such as montelukast, have been used to effectively treat patients with asthma. We have recently shown that mast cells are necessary modulators of innate immune responses to bacterial infection and an important component of this innate immune response may involve the production of CysLT. However, the effect of LRA on innate immune receptors, particularly on allergic effector cells, is unknown. This study determined the effect of CysLT on toll-like receptor (TLR) expression by the human mast cell line LAD2. Real-time PCR analysis determined that LTC4, LTD4 and LTE4 downregulated mRNA expression of several TLR. Specifically in human CD34+-derived human mast cells (HuMC), LTC4 inhibited expression of TLR1, 2, 4, 5, 6 and 7 while LTD4 inhibited expression of TLR1-7. Montelukast blocked LTC4-mediated downregulation of all TLR, suggesting that these effects were mediated by activation of the CysLT1 receptor (CysLT1R). Flow cytometry analysis confirmed that LTC4 downregulated surface expression of TLR2 which was blocked by montelukast. These data show that CysLT can modulate human mast cell expression of TLR and that montelukast may be beneficial for innate immune responses mediated by mast cells.

  11. The effect of anti-IgE treatment on in vitro leukotriene release in children with seasonal allergic rhinitis.

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    Kopp, Matthias Volkmar; Brauburger, Jens; Riedinger, Frank; Beischer, Dorothee; Ihorst, Gabriele; Kamin, Wolfgang; Zielen, Stefan; Bez; Friedrichs, Frank; Von Berg, Andrea; Gerhold, Kerstin; Hamelmann, Eckard; Hultsch; Kuehr, Joachim

    2002-11-01

    Binding of allergens with IgE to the IgE receptors on mast cells and basophils results in the release of inflammatory mediators as sulfidoleukotrienes (SLTs), triggering allergic cascades that result in allergic symptoms, such as asthma and rhinitis. We sought to investigate whether anti-IgE (Oma-lizumab), a humanized monoclonal anti-IgE antibody, in addition to specific immunotherapy (SIT) affects the leukotriene pathway. Ninety-two children (age range, 6-17 years) with sensitization to birch and grass pollens and with seasonal allergic rhinitis were included in a phase III, placebo- controlled, multicenter clinical study. All subjects were randomized to one of 4 treatment groups. Two groups subcutaneously received birch SIT and 2 groups received grass SIT for at least 14 weeks before the start of the birch pollen season. After 12 weeks of SIT titration, placebo or anti-IgE was added for 24 weeks. The primary clinical efficacy variable was symptom load (ie, the sum of daily symptom severity score and rescue medication score during pollen season). Blood samples taken at baseline and at the end of study treatment after the grass pollen season were used for separation of leukocytes in this substudy. After in vitro stimulation of the blood cells with grass and birch pollen allergens, SLT release (LTC4, LTD4, and LTE4) was quantified by using the ELISA technique. Before the study treatment, SLT release to birch and grass pollen exposure did not differ significantly among the 4 groups. Under treatment with anti-IgE + SIT-grass (n = 23), a lower symptom load occurred during the pollen season compared to placebo + SIT-grass (n = 24, P =.012). The same applied to both groups receiving birch SIT (n = 23 and n = 22, respectively; P =.03). At the end of treatment, the combination of anti-IgE plus grass SIT, as well as anti-IgE plus birch SIT, resulted in significantly lower SLT release after stimulation with the corresponding allergen (416 ng/L [5th-95th percentile, 1

  12. Relationship between leukotriene-modifying agent prescriptions dispensed and rate of suicide deaths by county in the US

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    Schumock GT

    2011-09-01

    Full Text Available Glen T Schumock1, Robert D Gibbons2, Todd A Lee1,3,4,6, Min J Joo4, Robert J Valuck5, Leslie T Stayner61Center for Pharmacoeconomic Research, and Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA; 2Center for Health Statistics, and Departments of Medicine and Health Studies, Pritzker School of Medicine, University of Chicago, Chicago, IL, USA; 3Center for Management of Complex Chronic Care, Hines VA Hospital, Hines, IL, USA; 4Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA; 5Department of Clinical Pharmacy, School of Pharmacy, University of Colorado, Aurora, CO, USA; 6Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, IL, USABackground: The US Food and Drug Administration has issued warnings about a potential link between leukotriene receptor-modifying agents (LTMA and suicide. These warnings are based on case reports and there is controversy about the association. While spontaneous reporting of suicide-related events attributed to LTMA has risen dramatically, these data may be biased by the warnings. The objective of this study was to explore the relationship between LTMA and suicide deaths using event data preceding the Food and Drug Administration warnings.Methods: We conducted a mixed-effects Poisson regression analysis of the association between LTMA prescriptions dispensed and suicide deaths at the county level. Counts of suicide deaths in each US county, stratified by race, age group, gender, and year were obtained from the National Center for Health Statistics for the period January 1, 1999 to December 31, 2006. Counts of LTMA prescriptions dispensed in each US county were obtained from IMS Health Incorporated. The model estimated the overall suicide rate conditional on LTMA use, adjusted for age, gender, race, year

  13. Leukotriene B4 omega-hydroxylase in human polymorphonuclear leukocytes. Partial purification and identification as a cytochrome P-450.

    Science.gov (United States)

    Shak, S; Goldstein, I M

    1985-09-01

    Human polymorphonuclear leukocytes (PMN) not only synthesize and respond to leukotriene B4 (LTB4), but also catabolize this mediator of inflammation rapidly and specifically by omega-oxidation. To characterize the enzyme(s) responsible for omega-oxidation of LTB4, human PMN were disrupted by sonication and subjected to differential centrifugation to yield membrane, granule, and cytosol fractions (identified by biochemical markers). LTB4 omega-hydroxylase activity was concentrated (together with NADPH cytochrome c reductase activity) only in the membrane fraction (specific activity increased 10-fold as compared to whole sonicates, 41% recovery). Negligible activity was detected in granule or cytosol fractions. LTB4 omega-hydroxylase activity in isolated PMN membranes was linear with respect to duration of incubation and protein concentration, was maximal at pH 7.4, had a Km for LTB4 of 0.6 microM, and was dependent on oxygen and on reduced pyridine nucleotides (apparent Km for NADPH = 0.5 microM; apparent Km for NADH = 223 microM). The LTB4 omega-hydroxylase was inhibited significantly by carbon monoxide, ferricytochrome c, SKF-525A, and Triton X-100, but was not affected by alpha-naphthoflavone, azide, cyanide, catalase, and superoxide dismutase. Finally, isolated PMN membranes exhibited a carbon monoxide difference spectrum with a peak at 452 nm. Thus, we have partially purified the LTB4 omega-hydroxylase in human PMN and identified the enzyme as a membrane-associated, NADPH-dependent cytochrome P-450.

  14. Tritium-labelled leukotriene B4 binding to the guinea-pig spleen membrane preparation: a rich tissue source for a high-affinity leukotriene B4 receptor site

    International Nuclear Information System (INIS)

    Cheng, J.B.; Cheng, E.I.; Kohi, F.; Townley, R.G.

    1986-01-01

    Intact human granulocytes contain a leukotriene (LT) B4 receptor binding site, but the limited supply of these cells could adversely affect further progress of the study of this receptor. To select a tissue homogenate rich for this site, we have characterized the binding of highly specific [ 3 H]LTB4 to guinea-pig spleen membranes and we have determined the ability of LTB4 to compete with [ 3 H]LTB4 for binding sites in the membranes of 10 nonspleen tissues. In the spleen membrane, MgCl2 and CaCl2 enhanced [ 3 H]LTB4 binding, but NaCl and KCl decreased it. Spleen [ 3 H] LTB4 binding was a function of protein concentration and was rapid, reversible, stereoselective and saturable. Kinetic analyses showed that the rate constant for association and dissociation at 25 0 C was 0.47 nM-1 min-1 and 0.099 min-1, respectively. A Scatchard plot of the data of the equilibrium experiment resulted a straight line with a dissociation constant of 1.8 nM and a density of 274 fmol/mg of protein. Moreover, the LTB4/[ 3 H]LTB4 competition study performed at 4 or 25 0 C revealed the inhibitory constant (Ki) of LTB4 to be in the nanomolar range. The rank order of agents competing for spleen [ 3 H]LTB4 binding was: LTB4 (Ki = 2.8 nM) greater than 20-hydroxy-LTB4 (23 nM) greater than LTA4 (48 nM) greater than LTA4 methyl ester (0.13 microM) greater than 20-carboxy-LTB4 (greater than 6.6 microM) greater than or equal to arachidonic acid (0.15mM) = FPL-55,712 and FPL-57,231 (0.1-0.2 mM). Competition studies further indicated that felodipine, a 1,4-dihyropyridine Ca++ channel blocker, exhibited micromolar inhibition of spleen [ 3 H]LTB4 binding

  15. Use of transdermal and intravenous granisetron and the ability of the Hesketh score to assess nausea and vomiting induced by multiday chemotherapy

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    Boccia RV

    2012-07-01

    Full Text Available Ralph V Boccia,1 Gemma Clark,2 Julian D Howell21Center for Cancer and Blood Disorders, Bethesda, MD, USA; 2ProStrakan Pharmaceuticals, Galashiels, UKPurpose: Hesketh scores define emetogenicity of single-agent and multiagent single-day chemotherapy. This analysis determined the emetogenicity of multiagent, multiday chemotherapy and the Granisetron Transdermal System (GTDS; Sancuso®.Methods: This was a retrospective analysis of a multicenter, randomized, double-blind, phase III noninferiority trial of GTDS versus oral granisetron in patients receiving 3 days of multiagent moderately or highly emetogenic chemotherapy, regardless of granisetron formulation. Emesis was defined as vomiting/retching or the use of rescue medication. Logistic regression and classification trees were used to determine the optimal combination of Hesketh scores over the multiagent, multiday regimens for the prediction of emesis.Results: Of 393 patients, 272 (69.2% were chemotherapy naïve. The most common types of cancer were lung (30.5% and gynecologic (21.9%. The most common chemotherapeutic regimen (in 14.2% of patients was cisplatin plus etoposide on days 1–3. The best binary emesis predictor was day 1 Hesketh score. Patients with a day 1 Hesketh score of 5 had the highest rate of emesis (62.5% versus patients with a score < 5 (31.7%. For patients with day 1 Hesketh score < 5, only 14.3% of those receiving only one drug on day 1 experienced emesis.Conclusion: Hesketh emetogenicity scores of individual agents are applicable to multiday, multiagent chemotherapeutic regimens in patients receiving antiemetics.Keywords: chemotherapy-induced nausea and vomiting, emetogenicity, granisetron, clinical trial, retrospective analysis

  16. Effects of thyroid hormone analogue and a leukotrienes pathway-blocker on renal ischemia/reperfusion injury in mice

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    Hadi Najah R

    2011-12-01

    Full Text Available Abstract Background Acute renal failure (ARF is an important clinical problem with a high mortality and morbidity. One of the primary causes of ARF is ischemia/reperfusion (I/R. Inflammatory process and oxidative stress are thought to be the major mechanisms causing I/R. MK-886 is a potent inhibitor of leukotrienes biosynthesis which may have anti-inflammatory and antioxidant effects through inhibition of polymorphonuclear leukocytes (PMNs infiltration into renal tissues. 3, 5-diiodothyropropionic acid (DITPA have evidences of improving effects on I/R in heart through modulation of cellular signaling in response to ischemic stress. The objective of present study was to assess the effects of MK-886 and DITPA on renal I/R injury. Methods A total of 24 Adult males of Swiss albino mice were randomized to four groups: I/R group (n = 6, mice underwent 30 minute bilateral renal ischemia and 48 hr reperfusion. Sham group (n = 6, mice underwent same anesthetic and surgical procedures except for ischemia induction. MK-886-treated group: (n = 6, I/R + MK-886 (6 mg/kg by intraperitoneal injection. DITPA-treated group: (n = 6, I/R + DITPA (3.75 mg/kg by intraperitoneal injection. After the end of reperfusion phase mice were sacrificed, blood samples were collected directly from the heart for determination of serum TNF-a, IL-6, urea and Creatinine. Both kidney were excised, the right one homogenized for oxidative stress parameters (MDA and GSH measurements and the left kidney fixed in formalin for histological examination. Results Serum TNF-α, IL-6, urea and Creatinine, kidney MDA levels and scores of histopathological changes were significantly (P 0.05 changes in levels of all study parameters as compared with that of I/R group. Conclusion The results of the present study show that MK-886 significantly ameliorated kidney damage that resulted from I/R. For DITPA, as its administration might not be successful, administration using a different protocol may

  17. Bone infected/inflamed conditions: Clinical experience with RP517, a Tc99m-leukotriene B4 receptor antagonist

    International Nuclear Information System (INIS)

    Soroa, V.; Nicolini, J.; Camin, L.; Ughetti, R.; Velasquez, M.

    2003-01-01

    Full text: Objectives: Tc 99m- RP517- is a receptor antagonist of Leukotriene B4 (LTB4) labelling predominantly neutrophils, in whole blood. The aim of this clinical trial was to obtain the best acquisition protocol and performance of this agent in detecting bone, joint and soft tissue infected / inflamed pathologies. Methods: RP517 was labelled with 15-20 mCi (555-740MBq) Tc99m per doses. Twenty-six patients studied (F 14, M 12) with range ages 19- 93, suspected of bone, joint and soft tissue infection (25) and one with fever of unknown origin (FUO). Laboratory data, anatomical images and one other scintiscan (MDP, Ga-67 or Tc99m- ciprofloxacin) were evaluated. Acquisition protocol: flow, 30 min, 1, 2, 3, 4 - 24h planar or Spect images as required. Results documented with histology, cultures or clinical follow up. Scans were classified as positive when abnormal uptake persisted in the 24h images or negative when positivity faded, or not detected in later images. Results: Labeling efficiency 86-90%. No adverse reactions encountered. Image protocol modified to a flow, 30 min, 4 and 24h images. Ten-fifteen % of in vivo leucocyte labelling at 1h. Early bile and intestinal excretion did not improve with cleansing enemas or food restrain. Late bone marrow activity is less visible than with in vitro leucocyte labeling. Only 16 patients had proven biopsies and cultures with coincident images in 8 True Positive; other 6 cases were True Negative, 2 False Negative (with positive Ga-67 and Tc99m-ciprofloxacin) and no False Positive. Sensitivity 80%, Specificity 100%. Conclusions: A kit should be produced in order to make it easily available. Pharmaceutically manipulation altering the excretion route could validate studies in abdominal infections and FUO that are now disesteemed. Protocol images must include 24h scans. Advantage of RP517 is the lack of cell labeling manipulation. Larger series must be studied to obtain statistics on joint bone and soft tissue infection

  18. Oenothera paradoxa defatted seeds extract and its bioactive component penta-O-galloyl-β-D-glucose decreased production of reactive oxygen species and inhibited release of leukotriene B4, interleukin-8, elastase, and myeloperoxidase in human neutrophils.

    Science.gov (United States)

    Kiss, Anna K; Filipek, Agnieszka; Czerwińska, Monika; Naruszewicz, Marek

    2010-09-22

    In this study, we analyzed ex vivo the effect of an aqueous extract of Oenothera paradoxa defatted seeds on the formation of neutrophil-derived oxidants. For defining active compounds, we also tested lypophilic extract constituents such as gallic acid, (+)-catechin, ellagic acid, and penta-O-galloyl-β-D-glucose and a hydrophilic fraction containing polymeric procyanidins. The anti-inflammatory potential of the extract and compounds was tested by determining the release from activated neutrophils of elastase, myeloperoxidase, interleukin-8 (IL-8), and leukotriene B4 (LTB4), which are considered relevant for the pathogenesis of cardiovascular diseases. The extract of O. paradoxa defatted seeds displays potent antioxidant effects against both 4β-phorbol-12β-myristate-α13-acetate- and formyl-met-leu-phenylalanine-induced reactive oxygen species production in neutrophils with IC50 values around 0.2 μg/mL. All types of polyphenolics present in the extract contributed to the extract antioxidant activity. According to their IC50 values, penta-O-galloyl-β-D-glucose was the more potent constituent of the extract. In cell-free assays, we demonstrated that this effect is partially due to the scavenging of O2- and H2O2 oxygen species. The extract and especially penta-O-galloyl-β-D-glucose significantly inhibit elastase, myeloperoxidase IL-8, and LTB4 release with an IC50 for penta-O-galloyl-β-D-glucose of 17±1, 15±1, 6.5±2.5, and around 20 μM, respectively. The inhibition of penta-O-galloyl-β-D-glucose on reactive oxygen species and especially on O2- production, myeloperoxidase, and chemoattractant release may reduce the interaction of polymorphonuclear leukocyte with the vascular endothelium and by that potentially diminish the risk of progression of atherosclerosis development.

  19. Immunocytochemical localization of glutamic acid decarboxylase (GAD) and substance P in neural areas mediating motion-induced emesis: Effects of vagal stimulation on GAD immunoreactivity

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    Damelio, F.; Gibbs, M. A.; Mehler, W. R.; Daunton, Nancy G.; Fox, Robert A.

    1991-01-01

    Immunocytochemical methods were employed to localize the neurotransmitter amino acid gamma-aminobutyric acid (GABA) by means of its biosynthetic enzyme glutamic acid decarboxylase (GAD) and the neuropeptide substance P in the area postrema (AP), area subpostrema (ASP), nucleus of the tractus solitarius (NTS), and gelatinous nucleus (GEL). In addition, electrical stimulation was applied to the night vagus nerve at the cervical level to assess the effects on GAD-immunoreactivity (GAR-IR). GAD-IR terminals and fibers were observed in the AP, ASP, NTS, and GEL. They showed pronounced density at the level of the ASP and gradual decrease towards the solitary complex. Nerve cells were not labelled in our preparations. Ultrastructural studies showed symmetric or asymmetric synaptic contracts between labelled terminals and non-immunoreactive dendrites, axons, or neurons. Some of the labelled terminals contained both clear- and dense-core vesicles. Our preliminary findings, after electrical stimulation of the vagus nerve, revealed a bilateral decrease of GAD-IR that was particularly evident at the level of the ASP. SP-immunoreactive (SP-IR) terminals and fibers showed varying densities in the AP, ASP, NTS, and GEL. In our preparations, the lateral sub-division of the NTS showed the greatest accumulation. The ASP showed medium density of immunoreactive varicosities and terminals and the AP and GEL displayed scattered varicose axon terminals. The electron microscopy revealed that all immunoreactive terminals contained clear-core vesicles which make symmetric or asymmetric synaptic contact with unlabelled dendrites. It is suggested that the GABAergic terminals might correspond to vagal afferent projections and that GAD/GABA and substance P might be co-localized in the same terminal allowing the possibility of a regulated release of the transmitters in relation to demands.

  20. In vivo effects of dexamethasone and indomethacin on neutrophil-induced alterations of nasal epithelial mucosubstances

    International Nuclear Information System (INIS)

    Hotchkiss, J.A.; Portereiko, J.V.; Harkema, J.R.

    1988-01-01

    Previous studies have shown that neutrophils migrating through rat nasal mucosal epithelium, in response to intranasal instillation of endotoxin, induce a transient decrease in stored epithelial mucosubstances. Prostaglandins and leukotrienes can either increase or decrease mucous secretion of airway epithelia in vitro. In this study, rats were treated with indomethacin a specific inhibitor of prostaglandin synthesis, or with dexamethasone, a general inhibitor of arachidonic acid metabolism, and challenged with intranasally instilled endotoxin. Dexamethasone alone or in combination with indomethacin, but not indomethacin alone, significantly altered the neutrophil response to intranasally instilled endotoxin and may have inhibited the neutrophil-induced decrease in stored mucosubstances. These data suggest that leukotrienes and possibly prostaglandins play a significant role in the coordinated response of the nasal mucosal epitholium to an acute inflammatory stimulus. (author)

  1. In vivo effects of dexamethasone and indomethacin on neutrophil-induced alterations of nasal epithelial mucosubstances

    Energy Technology Data Exchange (ETDEWEB)

    Hotchkiss, J A; Portereiko, J V; Harkema, J R

    1988-12-01

    Previous studies have shown that neutrophils migrating through rat nasal mucosal epithelium, in response to intranasal instillation of endotoxin, induce a transient decrease in stored epithelial mucosubstances. Prostaglandins and leukotrienes can either increase or decrease mucous secretion of airway epithelia in vitro. In this study, rats were treated with indomethacin a specific inhibitor of prostaglandin synthesis, or with dexamethasone, a general inhibitor of arachidonic acid metabolism, and challenged with intranasally instilled endotoxin. Dexamethasone alone or in combination with indomethacin, but not indomethacin alone, significantly altered the neutrophil response to intranasally instilled endotoxin and may have inhibited the neutrophil-induced decrease in stored mucosubstances. These data suggest that leukotrienes and possibly prostaglandins play a significant role in the coordinated response of the nasal mucosal epitholium to an acute inflammatory stimulus. (author)

  2. The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney disease.

    Science.gov (United States)

    Barden, Anne E; Shinde, Sujata; Burke, Valerie; Puddey, Ian B; Beilin, Lawrence J; Irish, Ashley B; Watts, Gerald F; Mori, Trevor A

    2018-03-22

    Neutrophils release leukotriene (LT)B 4 and myeloperoxidase (MPO) that may be important mediators of chronic inflammation in chronic kidney disease (CKD). The n-3 fatty acids (n-3 FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have the potential to attenuate inflammation through production of LTB 5 and the Specialized Proresolving Lipid Mediators (SPM) that promote the resolution of inflammation. In animal models, coenzyme Q10 (CoQ) also attenuates inflammation by reducing MPO and LTB 4 . This study evaluated the independent and combined effects of n-3 FA and CoQ supplementation on neutrophil leukotrienes, the pro-inflammatory eicosanoid 5-hydroxyeicosatetraenoic acid (5-HETE), SPM, and plasma MPO, in patients with CKD. In a double-blind, placebo-controlled intervention of factorial design, 85 patients with CKD were randomized to either n-3 FA (4 g), CoQ (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. Plasma MPO and calcium ionophore-stimulated neutrophil release of LTs, 5-HETE and SPM were measured at baseline and after 8 weeks. Seventy four patients completed the intervention. n-3 FA, but not CoQ, significantly increased neutrophil LTB 5 (P n-3 FA or CoQ. Plasma MPO was significantly reduced with n-3 FA alone (P = 0.013) but not when given in combination with CoQ. n-3 FA supplementation in patients with CKD leads to increased neutrophil release of LTB 5 and several SPM, as well as a reduction in plasma MPO that may have important implications for limiting chronic inflammation. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. [Treatment of ASS-Associated Polyposis (ASSAP) with a cysteinyl leukotriene receptor antagonist - a prospective drug study on its antiinflammatory effects].

    Science.gov (United States)

    Grundmann, T; Töpfner, M

    2001-10-01

    In a high rate of cases with recurrent polyposis an association with ASS-intolerance is detectable despite missing pulmonary symptoms. New examinations of a disturbed arachidonic acid metabolism lead to the development of new therapeutical options. Treatment with leukotriene-receptor antogonists (LTA) showed primarily good results in therapy of ASS-associated asthma. 18 patients with ASS-intolerance trias - diagnosed by oral provocation - were treated with the LTA Montelukast, after undergoing sinus surgery. Patients underwent a diagnostic pathway of provocation including four groups: recurrent chronic sinusitis, excessive polyposis, polyposis associated with asthma and anaphylactic symptoms after oral ASS-intake. Clinically we examined the following parameters periodically after sinus surgery: nasal and pulmonal symptoms by scoring levels, recurrency of polypoid hyperplasia by endoscopic follow-ups and serum ECP-levels. To evaluate antiinflammatory tissue effects of LTA EG1/EG2 labelled cells and cytokine levels of Interleukin 5 in mucosa samples of the lower turbinate were analysed under LTA-therapy. Under therapy with LTA we saw a beneficial effect on nasal and pulmonary symptoms and a significant reduction of recurrent polyposis in endoscopic examinations in relation to the untreated group. Results were proven by a permanent reduction of serum ECP-level. A reduction of the rate of EG2-positive cells according to decreased Interleukin 5 levels in the nasal mucosa unter LTA-treatment assumed antiinflammatory effects on ASS-associated polyposis. We could demonstrate antiinflammatory effects of Leukotriene-Receptor-Antagonists primarily during postoperative treatment of patients with ASS-associated nasal polyps.

  4. A Case of Montelukast-Induced Churg-Strauss Syndrome Associated with Liver Dysfunction

    Directory of Open Access Journals (Sweden)

    Keiji Matsui

    2011-01-01

    Full Text Available A 64-year-old woman was admitted to hospital due to protracted diarrhea and liver dysfunction. The patient was diagnosed as Churg-Strauss syndrome (CSS due to asthma, paranasal sinusitis, hypereosinophilia, and polyneuropathy. There was a history of taking montelukast, a leukotriene receptor antagonist (LTRA, which is thought to have some relationship with CSS. The liver biopsy specimen showed eosinophilic infiltration and centrolobular fatty change. In this paper, we review the relationship between LTRA and CSS. Several lines of evidence suggest that leukotriene plays an important role in maintaining neural tissues. We also review the potential relationship between centrolobular fatty change and pivoxil-containing antibiotics, which was prescribed for sinusitis before admission. Carnitine deficiency induced by pivoxil-containing agents may cause impaired fatty acid oxidation in mitochondria.

  5. Efficacy of granisetron and aprepitant in a patient who failed ondansetron in the prophylaxis of radiation induced nausea and vomiting: a case report.

    Science.gov (United States)

    Rowbottom, Leigha; Pasetka, Mark; McDonald, Rachel; Hunyh, Lise; Raman, Srinivas; DeAngelis, Carlo; Chow, Edward

    2015-01-01

    Radiotherapy-induced nausea and vomiting (RINV) is a toxicity that can occur in 40-80% of individuals who receive radiation treatment. Current guidelines recommend 5-hydroxytryptamine3 receptor antagonists (5-HT3 RAs) for prophylaxis of RINV for moderate and highly emetogenic radiotherapy; however, certain patients may suffer from RINV despite prophylaxis. This report details the case of a 47-year-old female with extensive bony involvement to the spine from breast cancer presenting with lower back pain. To palliate her symptoms, the patient underwent a course of irradiation to the lumbar spine and was prescribed ondansetron as an antiemetic. However, the patient experienced severe nausea and emesis and was subsequently switched to granisetron and aprepitant. The patient completed the remainder of the radiation treatment with no further emesis and minimal nausea, representing the first documented success of granisetron and aprepitant for RINV after failure on ondansetron. In chemotherapy, switching 5-HT3 RAs after failure on the first is successful in preventing chemotherapy-induced nausea and vomiting (CINV), yet this has not been previously reported in radiation. In this patient, granisetron and aprepitant were successful in substantially reducing nausea and preventing further emesis, and may represent an alternative antiemetic regimen for RINV prophylaxis and salvage.

  6. Suppression of Cisplatin-Induced Vomiting by Cannabis sativa in Pigeons: Neurochemical Evidences

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    Ihsan Ullah

    2018-03-01

    Full Text Available Cannabis sativa (CS, family Cannabinaceae has been reported for its anti-emetic activity against cancer chemotherapy-induced emesis in animal models and in clinics. The current study was designed to investigate CS for potential effectiveness to attenuate cisplatin-induced vomiting in healthy pigeons and to study the impact on neurotransmitters involved centrally and peripherally in the act of vomiting. High-performance liquid chromatography system coupled with electrochemical detector was used for the quantification of neurotransmitters 5-hydroxytryptamine (5HT, dopamine (DA and their metabolites; Di-hydroxy Phenyl Acetic acid (Dopac, Homovanillic acid (HVA, and 5-hydroxy indole acetic acid (5HIAA centrally in specific brain areas (area postrema and brain stem while, peripherally in small intestine. Cisplatin (7 mg/kg i.v. induce emesis without lethality across the 24 h observation period. CS hexane fraction (CS-HexFr; 10 mg/kg attenuated cisplatin-induced emesis ∼ 65.85% (P < 0.05; the reference anti-emetic drug, metoclopramide (MCP; 30 mg/kg, produced ∼43.90% reduction (P < 0.05. At acute time point (3rd h, CS-HexFr decreased (P < 0.001 the concentration of 5HT and 5HIAA in the area postrema, brain stem and intestine, while at 18th h (delayed time point CS-HexFr attenuated (P < 0.001 the upsurge of 5HT caused by cisplatin in the brain stem and intestine and dopamine in the area postrema. CS-HexFr treatment alone did not alter the basal neurotransmitters and their metabolites in the brain areas and intestine except 5HIAA and HVA, which were decreased significantly. In conclusion the anti-emetic effect of CS-HexFr is mediated by anti-serotonergic and anti-dopaminergic components in a blended manner at the two different time points, i.e., 3rd and 18th h in pigeons.

  7. Leukotriene-B4 concentrations in exhaled breath condensate and lung function after thirty minutes of breathing technically dried compressed air.

    Science.gov (United States)

    Neubauer, Birger; Struck, Niclas; Mutzbauer, Till S; Schotte, Ulrich; Langfeldt, Norbert; Tetzlaff, Kay

    2002-01-01

    In previous studies it had been shown that leukotriene-B4 [LTB4] concentrations in the exhaled breath mirror the inflammatory activity of the airways if the respiratory tract has been exposed to occupational hazards. In diving the respiratory tract is exposed to cold and dry air and the nasopharynx, as the site of breathing-gas warming and humidification, is bypassed. The aim of the present study was to obtain LTB4-concentrations in the exhaled breath and spirometric data of 17 healthy subjects before and after thirty minutes of technically dried air breathing at normobar ambient pressure. The exhaled breath was collected non-invasively, via a permanently cooled expiration tube. The condensate was measured by a standard enzyme immunoassay for LTB4. Lung function values (FVC, FEV1, MEF 25, MEF 50) were simultaneously obtained by spirometry. The measured pre- and post-exposure LTB4- concentrations as well as the lung function values were in the normal range. The present data gave no evidence for any inflammatory activity in the subjects' airways after thirty minutes breathing technically dried air.

  8. Lower leukotriene C4 levels in bronchoalveolar lavage fluid of asthmatic subjects after 2.5 years of inhaled corticosteroid therapy

    Directory of Open Access Journals (Sweden)

    Y. Oosterhoff

    1995-01-01

    Full Text Available Long-term treatment with inhaled corticosteroids has been shown to result in improvement of symptoms and lung function in subjects with asthma. Arachidonic acid (AA metabolites are thought to play a role in the pathophysiology of asthma. It was assessed whether differences could be found in bronchoalveolar lavage (BAL AA metabolite levels between subjects with asthma who were treated for 2.5 years with inhaled bronchodilators alone or in combination with inhaled corticosteroids. Prostaglandin (PGD2, PGF2α, 6-keto-PGF1α, thromboxane B2, leukotriene (LTC4 and LTB4 levels and cell numbers were assessed in BAL fluid from 22 non-smoking asthmatic subjects. They were participating in a randomized, double-blind multicentre drug trial over a period of 2.5 years. Results of the group treated with inhaled corticosteroids (CS+: beclomethasone 200 μg four times daily were compared with the other group (CS− which was treated with either ipratropium bromide (40 μg four times daily or placebo. BAL LTC4 levels of asthmatic subjects were significantly lower after 2.5 years inhaled corticosteroid therapy (CS+, 9(1–17 pg/ml vs. CS−, 16(6-53 pg/ml; p = 0.01. The same trend was observed for the PGD2 levels. The results suggest that inhaled corticosteroids may exert their beneficial effect on lung function via a mechanism in which inhibition of LTC4 synthesis in the airways is involved.

  9. Effects of Xingbi gel on leukotriene E4 and immunoglobulin E production and nasal eosinophilia in a guinea pig model for allergic rhinitis.

    Science.gov (United States)

    Ai, Si; Zheng, Jian; Chu, Ke-Dan; Zhang, Hong-Sheng

    2015-06-01

    Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal airways.Many therapies do not have immediate effects,even which have side-effects.However,the effects of Xingbi gel for the treatment of AR was investigated. We investigated the effects of Xingbi gel on serum levels of leukotriene E4 (LTE4) and immunoglobulin E (IgE), as well as eosinophil counts in the nasal mucosa using a guinea pig model of allergic rhinitis (AR). In addition to a healthy control group without AR, guinea pigs with AR were randomly divided into untreated AR control group, low-dose Xingbi gel (0.2483 g/mL) group, high-dose Xingbi gel (0.4966 g/mL) group, and budesonide group. Compared to the healthy controls, untreated AR guinea pigs had significantly higher ethology scores, serum LTE4 and IgE levels, and nasal mucosa eosinophil counts (p guinea pigs (p production and reducing eosinophilia in the nasal mucosa.

  10. Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting over multiple cycles of moderately or highly emetogenic chemotherapy.

    Science.gov (United States)

    Rapoport, Bernardo; Schwartzberg, Lee; Chasen, Martin; Powers, Dan; Arora, Sujata; Navari, Rudolph; Schnadig, Ian

    2016-04-01

    Rolapitant, a novel neurokinin-1 receptor antagonist (RA), was shown to protect against delayed chemotherapy-induced nausea and vomiting (CINV) during the first cycle of moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) in randomized, double-blind trials. This analysis explored the efficacy and safety of rolapitant in preventing CINV over multiple cycles of MEC or HEC. Patients in one phase III MEC, one phase II HEC, and two phase III HEC clinical trials were randomized to receive oral rolapitant (180 mg) or placebo in combination with a 5-hydroxytryptamine type 3 RA and dexamethasone. Regardless of response in cycle 1, patients could continue the same antiemetic treatment for up to six cycles. On days 6-8 of each subsequent chemotherapy cycle, patients reported the incidence of emesis and/or nausea interfering with normal daily life. Post hoc analyses of pooled safety and efficacy data from the four trials were performed for cycles 2-6. Significantly more patients receiving rolapitant than control reported no emesis or interfering nausea (combined measure) in cycles 2 (p = 0.006), 3 (p cycles 1-6, time-to-first emesis was significantly longer with rolapitant than with control (p cycles 2-6 was similar in rolapitant (5.5%) and control (6.8%) arms. No cumulative toxicity was observed. Over multiple cycles of MEC or HEC, rolapitant provided superior CINV protection and reduced emesis and nausea interfering with daily life compared with control and remained well tolerated. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Differential clinical pharmacology of rolapitant in delayed chemotherapy-induced nausea and vomiting (CINV

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    Rashad N

    2017-03-01

    Full Text Available Noha Rashad,1 Omar Abdel-Rahman2 1Medical Oncology Department, Maadi Armed Forces Hospital, 2Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt Abstract: Rolapitant is a highly selective neurokinin-1 receptor antagonist, orally administered for a single dose of 180 mg before chemotherapy with granisetron D1, dexamethasone 8 mg BID on day 2–4. It has a unique pharmacological characteristic of a long plasma half-life (between 163 and 183 hours; this long half-life makes a single use sufficient to cover the delayed emesis risk period. No major drug–drug interactions between rolapitant and dexamethasone or other cytochrome P450 inducers or inhibitors were observed. The clinical efficacy of rolapitant was studied in two phase III trials in highly emetogenic chemotherapy and in one clinical trial in moderately emetogenic chemotherapy. The primary endpoint was the proportion of patients achieving a complete response (defined as no emesis or use of rescue medication in the delayed phase (>24–120 hours after chemotherapy. In comparison to granisetron (10 µg/kg intravenously and dexamethasone (20 mg orally on day 1, and dexamethasone (8 mg orally twice daily on days 2–4 and placebo, rolapitant showed superior efficacy in the control of delayed and overall emesis. This review aims at revising the pharmacological characteristics of rolapitant, offering an updated review of the available clinical efficacy and safety data of rolapitant in different clinical settings, highlighting the place of rolapitant in the management of chemotherapy-induced nausea and vomiting (CINV among currently available guidelines, and exploring the future directions of CINV management. Keywords: nausea, vomiting, chemotherapy, rolapitant, CINV

  12. MAC-1 Glycoprotein Family mediates adherence of neutrophils to endothelial cells stimulated by leukotriene B/sub 4/ and platelet activating factor

    Energy Technology Data Exchange (ETDEWEB)

    Tonnesen, M.G.; Anderson, D.C.; Springer, T.A.; Knedler, A.; Avdi, N.; Henson, P.M.

    1986-03-01

    The process of neutrophil (N) adhesion to and migration through endothelium (EC), an early event in the induction of the acute inflammatory response, has been attributed to the generation of extravascular chemoattractant peptides and lipids. Although both leukotriene B/sub 4/ (LTB/sub 4/) and platelet activating factor (PAF) enhance N adherence to EC, the mechanisms involved in this interaction are still not completely understood. Since the MAC-1 Glycoprotein (GP) Family has recently been shown to be required for a variety of adherence-dependent functions of stimulated N, the authors questioned whether these adherence-associated GP might be involved in N adherence to EC stimulated by LTB/sub 4/ or PAF. Using a microtiter adherence assay with /sup 111/In labeled N, they assessed the ability of N from patients with MAC-1, LFA-1 Deficiency to adhere to monolayers of human omental microvascular or umbilical vein EC as well as to serum-coated plastic. Patient N exhibited markedly diminished adherence in response to LTB/sub 4/ or PAF compared to normal controls. LTB/sub 4/ and PAF enhanced expression of the MAC-1 GP Family on the surface of normal N as determined by flow cytofluorimetry using a monoclonal antibody (TS1/18) to the GP common beta subunit. In addition TS1/18 (20 ..mu..g/ml) completely inhibited N adherence stimulated by either LTB/sub 4/ (10/sup -8/M) or PAF(10/sup -11/M). Thus, the MAC-1 GP Family appears to be important in chemotactic factor regulation of N adherence to EC.

  13. A new method to evaluate anti-allergic effect of food component by measuring leukotriene B4 from a mouse mast cell line.

    Science.gov (United States)

    Takasugi, Mikako; Muta, Emi; Yamada, Koji; Arai, Hirofumi

    2018-02-01

    Leukotrienes (LTs), chemical mediators produced by mast cells, play an important role in allergic symptoms such as food allergies and hay fever. We tried to construct an evaluation method for the anti-LTB 4 activity of chemical substances using a mast cell line, PB-3c. PB-3c pre-cultured with or without arachidonic acid (AA) was stimulated by calcium ionophore (A23187) for 20 min, and LTB 4 production by the cells was determined by HPLC with UV detection. LTB 4 was not detected when PB-3c was pre-cultured without AA. On the other hand, LTB 4 production by PB-3c pre-cultured with AA was detectable by HPLC, and the optimal conditions of PB-3c for LTB 4 detection were to utilize the cells pre-cultured with 50 µM AA for 48 h. MK-886 (5-lipoxygenase inhibitor) completely inhibited LTB 4 production, but AACOCF 3 (phospholipase A 2 inhibitor) slightly increased LTB 4 production, suggesting that LTB 4 was generated from exogenous free AA through 5-lipoxygenase pathway. We applied this technique to the evaluation of the anti-LTB 4 activity of food components. PB-3c pre-cultured with 50 µM AA for 48 h was stimulated with A23187 in the presence of 50 µM soybean isoflavones (daidzin, genistin, daidzein, and genistein), equol, quercetin, or kaempferol. Genistein, equol, quercetin, and kaempferol strongly inhibited LTB 4 production without cytotoxicity. These results suggest that a new assay system using PB-3c is convenient to evaluate LTB 4 inhibition activity by food components. This method could be utilized for elucidation of the mechanisms of LTB 4 release suppression by food components such as flavonoids and the structure-activity relationship.

  14. Physiological bases and treatment to the radiation-induced emetic reflex

    International Nuclear Information System (INIS)

    Mulen Napoles, Barbara M.; Torres Babie, Priscilla; Ropero Toirac, Ramon de J.

    2002-01-01

    In the course of the specific oncologic treatment, there are frequent complications such as nausea and vomiting. The radiation-induced emetic reflex depends on various factors: primary site of radiation, administered dose, fractioning, irradiated volume, the sensory and psychic characteristics of the patient as well as the chemotherapy association. It is known that the afferent path to the so-called center of vomiting is determined by chemical mediators, protuberance receptors of the intracranial pressure and the unleashing chemoreceptor zone. In radiation-induced emesis, the exact mechanism is yet to be determined but it is known that radiation stimulates the production of chemical mediators and serotonin released by enterochromaffin cells that act upon the center of vomiting and vagal nucleus. Most of patients who are exposed to irradiation of their upper and middle hemibody as well as all the patients exposed to whole-body irradiation present with nausea and vomiting. The therapeutical anti-emetic recommendations are based on the neurochemical control of vomiting and the emetogenic effect of radiotherapy. 5HT3 receptor-antagonists are evaluated as effective agents in the control of radiation-induced emesis

  15. Mast cell mediators in citric acid-induced airway constriction of guinea pigs

    International Nuclear Information System (INIS)

    Lin, C.-H.; Lai, Y.-L.

    2005-01-01

    We demonstrated previously that mast cells play an important role in citric acid (CA)-induced airway constriction. In this study, we further investigated the underlying mediator(s) for this type of airway constriction. At first, to examine effects caused by blocking agents, 67 young Hartley guinea pigs were divided into 7 groups: saline + CA; methysergide (serotonin receptor antagonist) + CA; MK-886 (leukotriene synthesis inhibitor) + CA; mepyramine (histamine H 1 receptor antagonist) + CA; indomethacin (cyclooxygenase inhibitor) + CA; cromolyn sodium (mast cell stabilizer) + CA; and compound 48/80 (mast cell degranulating agent) + CA. Then, we tested whether leukotriene C 4 (LTC 4 ) or histamine enhances CA-induced airway constriction in compound 48/80-pretreated guinea pigs. We measured dynamic respiratory compliance (Crs) and forced expiratory volume in 0.1 s (FEV 0.1 ) during either baseline or recovery period. In addition, we detected histamine level, an index of pulmonary mast cell degranulation, in bronchoalveolar lavage (BAL) samples. Citric acid aerosol inhalation caused decreases in Crs and FEV 0.1 , indicating airway constriction in the control group. This airway constriction was significantly attenuated by MK-886, mepyramine, cromolyn sodium, and compound 48/80, but not by either methysergide or indomethacin. Both LTC 4 and histamine infusion significantly increased the magnitude of CA-induced airway constriction in compound 48/80-pretreated guinea pigs. Citric acid inhalation caused significant increase in histamine level in the BAL sample, which was significantly suppressed by compound 48/80. These results suggest that leukotrienes and histamine originating from mast cells play an important role in CA inhalation-induced noncholinergic airway constriction

  16. Stimulus-selective regulation of human mast cell gene expression, degranulation and leukotriene production by fluticasone and salmeterol.

    Directory of Open Access Journals (Sweden)

    Adriana Catalli

    Full Text Available Despite the fact that glucocorticoids and long acting beta agonists are effective treatments for asthma, their effects on human mast cells (MC appear to be modest. Although MC are one of the major effector cells in the underlying inflammatory reactions associated with asthma, their regulation by these drugs is not yet fully understood and, in some cases, controversial. Using a human immortalized MC line (LAD2, we studied the effects of fluticasone propionate (FP and salmeterol (SM, on the release of early and late phase mediators. LAD2 cells were pretreated with FP (100 nM, SM (1 µM, alone and in combination, at various incubation times and subsequently stimulated with agonists substance P, C3a and IgE/anti-IgE. Degranulation was measured by the release of β-hexosaminidase. Cytokine and chemokine expression were measured using quantitative PCR, ELISA and cytometric bead array (CBA assays. The combination of FP and SM synergistically inhibited degranulation of MC stimulated with substance P (33% inhibition compared to control, n = 3, P<.05. Degranulation was inhibited by FP alone, but not SM, when MC were stimulated with C3a (48% inhibition, n = 3, P<.05. As previously reported, FP and SM did not inhibit degranulation when MC were stimulated with IgE/anti-IgE. FP and SM in combination inhibited substance P-induced release of tumor necrosis factor (TNF, CCL2, and CXCL8 (98%, 99% and 92% inhibition, respectively, n = 4, P<.05. Fluticasone and salmeterol synergistically inhibited mediator production by human MC stimulated with the neuropeptide substance P. This synergistic effect on mast cell signaling may be relevant to the therapeutic benefit of combination therapy in asthma.

  17. Measurement of tumor necrosis factor-α, leukotriene B4, and interleukin 8 in the exhaled breath condensate in patients with acute exacerbations of chronic obstructive pulmonary disease

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    Fanny WS Ko

    2008-12-01

    Full Text Available Fanny WS Ko1, Ting-Fan Leung2, Gary WK Wong2, Jenny Ngai1, Kin W To1, Susanna Ng1, David SC Hui11Department of Medicine and Therapeutics; 2Department of Pediatrics, The Chinese University of Hong Kong, Hong KongBackground: Assessment of airway inflammation in the clinical course of acute exacerbations of chronic obstructive pulmonary disease (AECOPD may advance our understanding of the pathogenesis and treatment.Objectives: To assess airway inflammation in patients during the course of AECOPD by serial analyses of their exhaled breath condensates (EBC.Methods: Twenty-six patients with AECOPD (22 males, mean[SD] percentage predicted forced expiratory volume in one second (FEV1 44.8 [14.3], 11 with stable COPD, and 14 age and sex-matched healthy controls were studied. Patients with AECOPD were treated with systemic steroid and antibiotic for 7 days. EBC was collected from each patient with AECOPD on Day 5, 14, 30, and 60 post-hospitalization using EcoScreen (VIASYS Healthcare, USA during tidal breathing over 10 minutes. Concentrations of tumor necrosis factor-α (TNF-α, leukotriene B4 (LTB4, and interleukin-8 (IL-8 were measured by enzyme-linked immunosorbent assay.Results: The median (IQR of TNF-α level on Day 5 was 5.08 (3.80–6 .32 pg/ml, which was lower than on Day 14 (5.84 [4.91–9.14] pg/ml, p = 0.017, Day 30 (6.14 [3.82–7.67] pg/ml, p = 0.045, and Day 60 (5.60 [4.53–8.80] pg/ml, p = 0.009. On Day 60, subjects receiving inhaled corticosteroid (ICS had a lower level of TNF-α than those who were not (4.82 [4.06–5.65] vs 7.66 [5.48–10.9] pg/ml, p = 0.02. EBC LTB4 level did not change significantly during recovery from AECOPD whereas IL-8 was mostly undetectable.Conclusions: EBC TNF-α level was low in patients receiving systemic steroid and antibiotic therapy for AECOPD. These findings suggest a potential role for serial EBC TNF-α for noninvasive monitoring of disease activity.Keywords: COPD, exacerbation, exhaled breath

  18. Leucocyte labeling: Preliminary clinical evaluation of RP517, the 99mTc-Leukotriene B4 receptor antagonist for infection/inflammation

    International Nuclear Information System (INIS)

    Soroa, V.E.; Velasquez, M.H.; Nicolini, J.; Ughetti, R.; Camin, L.

    2002-01-01

    99mTc- Leukotriene B4 (LTB4) is a receptor antagonist RP517 that labels predominantly neutrophils, in whole blood. This new radiopharmaceutical has been developed for imaging infection and inflammation. Aim: We conducted this clinical trial to obtain the best protocol imaging and the efficacy of this novel agent in the detection of suspected infected/inflamed patients. Materials and Methods: RP517 was labelled with 15-20 mCi (555-740 MBq) 99mTc for each patient, with a labeling efficiency of 86-95%. Nine patients studied (F 3, M 6) with ages 45-83, suspected of bone, joint and soft tissue infection (8) and one with fever of unknown origin (FUO). Laboratory, anatomical images and one other scintiscan (MDP, Gallium or 99mTc-ciprofloxacin) were used for evaluation. Acquisition protocol: flow, 30 min, 1, 2, 3, 4 - 24h planar or SPECT images if required. Results were compared to histology, cultures, the clinical derivation and follow up. Scans were classified as positive if abnormal uptake persisted through the 24h images or negative when absent pathological uptake or when positivity faded in later images. Results: No adverse reaction encountered. Image protocol modified to a flow, 30 min, 4 and 24h acquisitions. Early bladder excretion and intestinal activity requires previous cleansing enemas and food restrain. Late bone marrow activity is less visible than with in vitro leucocyte labeling. Coincident images were obtained in 3 True Positive, in 5 True Negative except in a hip prosthesis where Gallium and 99mTc-ciprofloxacin showed positivity and RP517 was False negative. Conclusions: A kit should be produced in order to make it available for Nuclear Medicine Departments. Known advantages of RP517 is the lack of in vitro cell labeling manipulation. We do not recommend investigation of FUO or abdominal pathologies. A larger series must be studied in order to be able to obtain statistics on joint bone and soft tissue infection/inflammation where this compound seems to be

  19. Urinary leukotriene E(4), eosinophil protein X, and nasal eosinophil cationic protein are not associated with respiratory symptoms in 1-year-old children.

    Science.gov (United States)

    Wojnarowski, C; Halmerbauer, G; Mayatepek, E; Gartner, C; Frischer, T; Forster, J; Kuehr, J

    2001-09-01

    Eosinophilic airways inflammation forms the pathophysiologic basis for a proportion of children at risk of developing recurrent wheezing. Early preventive measures and/or anti-inflammatory treatment may be guided by the identification of such children. We aimed to study the relationship between respiratory symptoms and indirect markers of airway inflammation. We measured eosinophil protein X (EPX) and leukotriene E(4) (LTE(4)) in urine, as well as eosinophil cationic protein (ECP) in nasal lavages, in a random sample of 1-year-old children with a family history of atopy who participated in an international multicenter study on the prevention of allergy in Europe. For urine analyses, 10 children with upper respiratory illness and 19 healthy children without a family history of atopy were also enrolled. Endogenous urinary LTE(4) was separated by HPLC and determined by enzyme immunoassay with a specific antibody. The concentrations of nasal ECP and urinary EPX were determined by RIA analysis. One hundred and ten children (mean age: 1.05+/-0.1 years) were enrolled. Prolonged coughing during the first year of life was reported in 29 children, wheezy breathing in 17 children, and dry skin in 33 children. A doctor's diagnosis of wheezy bronchitis was given to 17 children. Sensitization to dust mites (specific IgE > or =1.43 ML/units) was detected in two children. Children with a doctor's diagnosis of atopic dermatitis within the first 12 months of life (n=6) had significantly higher urinary EPX than children without this (66.7 vs 30.1 microg/mmol creatinine, P=0.01). Urinary excretion of EPX and LTE4 showed a weak correlation (r=0.22, P=0.02). There were no significant differences in urinary excretion of EPX and LTE(4) or nasal ECP between children with and without respiratory symptoms (P>0.1). At the age of 1 year, urinary EPX is increased in children with atopic dermatitis. With regard to respiratory symptoms, urinary and nasal inflammatory parameters are not helpful in

  20. Aprepitant: a promising antiemetic for prevention of chemotherapy-induced nausea and vomiting

    International Nuclear Information System (INIS)

    Aseeri, Mohamad A.

    2006-01-01

    Most patients who undergo chemotherapy have noted that nausea and vomiting are the most feared and distressing side-effects of cancer treatment (1). Nausea and vomiting from chemotherapy can be classified as acute, delayed, or anticipatory. Acute emesis generally occurs within 24 hours of chemotherapy administration; while delayed nausea and vomiting begin 24 hours after chemotherapy and may continue for up to one week. Anticipatory emesis occurs prior to chemotherapy in patients who anticipate another episode by sight, odors or memory of the place where acute nausea and vomiting occurred (2, 3). Different neurotransmitters found in the gastrointestinal tract (GIT) and central nervous system (CNS) mediate the pathophysiology of chemotherapy induced nausea and vomiting (CINV). These include dopamine, histamine, acetycholine, serotonin, and substance P; which act directly and indirectly on the vomiting center located in the lateral reticular formation of the medulla (1, 4). Substance P is a member of the tachykinins family of neuropeptides. The biological activity of this substance is to induce vomiting mediated by neurokinin-1 (NK1) receptors located primarily in the GIT and the CNS (5). Both Nk1 receptors and substance P play a significant role in the pathogenesis of acute and delayed CINV. (author)

  1. A double-blind randomised cross-over comparison of nabilone and metoclopramide in the control of radiation-induced nausea

    International Nuclear Information System (INIS)

    Priestman, S.G.; Priestman, T.J.; Canney, P.A.

    1987-01-01

    Forty patients who were suffering from radiation induced emesis were entered into a prospectively randomised double-blind cross-over study comparing nabilone with metoclopramide. Only patients who had at least five treatments remaining of their planned course of irradiation were randomised, in order to allow an adequate time to monitor the degree of symptom control and any adverse effects of the two drugs. Patient characteristics and the incidence and severity of nausea and vomiting were similar for the two groups. There was no difference in the efficacy of the two drugs but the incidence and severity of adverse reactions was significantly greater in those patients who received nabilone. (author)

  2. Sulfite induces release of lipid mediators by alveolar macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Beck-Speier, I.; Dayal, N.; Maier, L. [GSF - National Research Center for Environment and Health, Neuherberg (Germany). Inst. for Inhalation Biology; Denzlinger, C. [Tuebingen Univ. (Germany). Dept. II, Medical Clinic; Haberl, C. [Tuebingen Univ. (Germany). Dept. III, Medical Clinic

    1998-03-01

    Air pollutants are supposed to modulate physiological responses of alveolar macrophages (AM). This study was addressed to the question whether at neutral pH sulfur(IV) species in comparison to sulfur(VI) species cause AM to release proinflammatory mediators and which pathways are involved in their generation. Supernatants obtained from canine AM treated with sulfite (0.1 mM to 2 mM) enhanced the respiratory burst of canine neutrophils, measured by lucigenin-dependent chemiluminescence, whereas supernatants derived from AM treated with sulfate (1 mM) did not. The neutrophil-stimulating activity released by sulfite-treated AM consisted of platelet-activating factor (PAF) and leukotriene B{sub 4} (LTB{sub 4}) as shown by desensitization of the platelet-activating factor (PAF) and leukotriene B{sub 4} (LTB{sub 4}) as shown by desensitization of the corresponding receptors. Inhibitors of phospholipase A{sub 2} substantially suppressed release of neutrophil-stimulating activity by sulfite-treated AM. Inhibition of 5-lipoxygenase in sulfite-treated AM also reduced neutrophil-stimulating activity, while inhibition of cyclooxygenase had no effect. In conclusion, sulfite induces AM to release lipid mediators via phospholipase A{sub 2}- and 5-lipoxygenase-dependent pathways. These mediators activate neutrophils via the receptors for PAF and LTB{sub 4}. (orig.)

  3. Urinary metabolites of histamine and leukotrienes before and after placebo-controlled challenge with ASA and food additives in chronic urticaria patients.

    Science.gov (United States)

    Di Lorenzo, G; Pacor, M L; Vignola, A M; Profita, M; Esposito-Pellitteri, M; Biasi, D; Corrocher, R; Caruso, C

    2002-12-01

    The recovery of mediator metabolites from urine has the potential to provide a rapid, safe, and easily available index of release of mediators. We aimed to determine urinary metabolites of both histamine and leukotrienes (LTs) in patients affected by chronic urticaria (CU). Twenty patients with CU were studied. They were selected on the basis of double-blind placebo-controlled challenge (DBPC) with acetyl salicylic acid (ASA) and food additives. Ten patients (group B) were negative to both challenges. Ten patients (group C) presented urticaria and/or the appearance of angioedema during or 24 h after challenge, with reactions to ASA (five patients) or food additives (five patients). We recruited 15 healthy volunteers as controls (group A). During a second challenge, groups B and C were challenged double-blind with a single dose of ASA, or a specific food additive, or placebo. The healthy group was challenged only with a placebo (talc capsule). Patients in groups B and C were challenged twice: with placebo (as groups B1 and C1) and with ASA (groups B2 and C2) or food additives (C2). Four samples of urine were collected; one during the night before the specific or sham challenge (baseline), and three at 2, 6 and 24 h after the challenge. Urinary methylhistamine (N-MH) and LTE4 were analyzed and normalized for urinary creatinine. For urinary N-MH at baseline, there was a significant difference only between group A and groups B1, B2, C1 and C2 (A vs. B1, P < 0.0001; A vs. B2, P < 0.0001; A vs. C1, P < 0.0001; A vs. C2, P < 0.0001). We detected a significant variation in urinary methylhistamine excretion only in group C2 after 2 h, 6 h and 24 h (P < 0.0001). However, no variations were observed in N-MH excretion rate in the other groups (A, B1, C1) after challenge with placebo, and in B2 after challenge with ASA 20 mg. For urinary LTE4 at baseline no differences were found between the mean values for the different groups. After specific challenge, only C2 patients showed

  4. Exercise-induced asthma: critical analysis of the protective role of montelukast

    Directory of Open Access Journals (Sweden)

    Terrence W Carver Jr

    2009-10-01

    Full Text Available Terrence W Carver JrThe Children’s Mercy Hospital and Clinics, Kansas City, MO, USAAbstract: Exercise-induced asthma/exercise-induced bronchospasm (EIA/EIB is a prevalent and clinically important disease affecting young children through older adulthood. These terms are often used interchangeably and the differences are not clearly defined in the literature. The pathogenesis of EIA/EIB may be different in those with persistent asthma compared to those with exercise-induced symptoms only. The natural history of EIA is unclear and may be different for elite athletes. Leukotriene biology has helped the understanding of EIB. The type and intensity of exercise are important factors for EIB. Exercise participation is necessary for proper development and control of EIA is recommended. Symptoms of EIB should be confirmed by proper testing. Biologic markers may also be helpful in diagnosis. Not all exercise symptoms are from EIB. Many medication and nonpharmacologic treatments are available. Asthma education is an important component of managing EIA. Many medications have been tested and the comparisons are complicated. Montelukast is a US Food and Drug Administration-approved asthma and EIB controller and has a number of potential advantages to other asthma medications including short onset of action, ease of use, and lack of tolerance. Not all patients improve with montelukast and rescue medication should be available.Keywords: exercise, asthma, montelukast, Singulair, bronchospasm, leukotrienes

  5. Mechanism of gastrointestinal abnormal motor activity induced by cisplatin in conscious dogs.

    Science.gov (United States)

    Ando, Hiroyuki; Mochiki, Erito; Ohno, Tetsuro; Yanai, Mitsuhiro; Toyomasu, Yoshitaka; Ogata, Kyoichi; Tabe, Yuichi; Aihara, Ryuusuke; Nakabayashi, Toshihiro; Asao, Takayuki; Kuwano, Hiroyuki

    2014-11-14

    To investigate whether 5-hydroxytryptamine (serotonin; 5-HT) is involved in mediating abnormal motor activity in dogs after cisplatin administration. After the dogs had been given a 2-wk recovery period, all of them were administered cisplatin, and the motor activity was recorded using strain gauge force transducers. Blood and intestinal fluid samples were collected to measure 5-HT for 24 h. To determine whether 5-HT in plasma or that in intestinal fluids is more closely related to abnormal motor activity we injected 5-HT into the bloodstream and the intestinal tract of the dogs. Cisplatin given intravenously produced abnormal motor activity that lasted up to 5 h. From 3 to 4 h after cisplatin administration, normal intact dogs exhibited retropropagation of motor activity accompanied by emesis. The concentration of 5-HT in plasma reached the peak at 4 h, and that in intestinal fluids reached the peak at 3 h. In normal intact dogs with resection of the vagus nerve that were administered kytril, cisplatin given intravenously did not produce abnormal motor activity. Intestinal serotonin administration did not produce abnormal motor activity, but intravenous serotonin administration did. After the intravenous administration of cisplatin, abnormal motor activity was produced in the involved vagus nerve and in the involved serotonergic neurons via another pathway. This study was the first to determine the relationship between 5-HT and emesis-induced motor activity.

  6. Neutrophil-induced human bronchial hyperresponsiveness in vitro--pharmacological modulation.

    Science.gov (United States)

    Hughes, J M; McKay, K O; Johnson, P R; Tragoulias, S; Black, J L; Armour, C L

    1993-04-01

    Although it has been postulated that inflammatory cells cause the bronchial hyperresponsiveness which is diagnostic of asthma, until recently there has been little direct evidence of such a link. We have recently shown that calcium ionophore-activated human neutrophils and eosinophils can induce a state of human airway hyperresponsiveness in vitro. In this study we have shown that the anti-inflammatory agent nedocromil sodium, 10(-7) M, inhibited the hyperresponsiveness induced by products released from ionophore activated neutrophils but did not inhibit the release of leukotriene B4 from the same cells. Neutrophil-induced bronchial hyperresponsiveness was also inhibited by pre-treatment of the bronchial tissues with a thromboxane A2 and prostaglandin receptor antagonist, GR32191, 10(-7) M. These findings indicate that cyclooxygenase products are involved in bronchial hyperresponsiveness induced by inflammatory cell products in vitro and that their release can be inhibited by nedocromil sodium.

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

    Energy Technology Data Exchange (ETDEWEB)

    Salvo, Nadia; Doble, Brett [Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario (Canada); Khan, Luluel [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Amirthevasar, Gayathri [Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario (Canada); Dennis, Kristopher [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Pasetka, Mark; DeAngelis, Carlo [Department of Oncology Pharmacy, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Tsao, May [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Chow, Edward, E-mail: Edward.Chow@sunnybrook.ca [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada)

    2012-01-01

    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. Relative 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 the NK

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

    International Nuclear Information System (INIS)

    Salvo, Nadia; Doble, Brett; Khan, Luluel; Amirthevasar, Gayathri; Dennis, Kristopher; Pasetka, Mark; DeAngelis, Carlo; Tsao, May; Chow, Edward

    2012-01-01

    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. Relative 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

  9. Challenges in Clinical Management of Radiation-Induced Illnesses in Exploration Spaceflight

    Science.gov (United States)

    Blue, Rebecca; Chancellor, Jeffery; Suresh, Rahul; Carnell, Lisa; Reyes, David; Nowadly, Craig; Antonsen, Erik

    2018-01-01

    Historical solar particle events (SPEs) provide context for some understanding of acute radiation exposure risk to astronauts traveling outside of low Earth orbit. Modeling of potential doses delivered to exploration crewmembers anticipates limited radiation-induced health impacts, including prodromal symptoms of nausea, emesis, and fatigue, but suggests that more severe clinical manifestations are unlikely. Recent large animal-model research in space-analogs closely mimicking SPEs has identified coagulopathic events independent of the hematopoietic sequelae of higher radiation doses, similar in manifestation to disseminated intravascular coagulation (DIC). We explored the challenges of clinical management of radiation-related clinical manifestations, using currently accepted modeling techniques and anticipated physiological sequelae, to identify medical capabilities needed to successfully manage SPE-induced radiation illnesses during exploration spaceflight.

  10. Mast cells in citric acid-induced cough of guinea pigs

    International Nuclear Information System (INIS)

    Lai, Y.-L.; Lin, T.-Y.

    2005-01-01

    It was demonstrated previously that mast cells play an important role in citric acid (CA)-induced airway constriction. To investigate the role of mast cells in CA-induced cough, three experiments were carried out in this study. In the first experiment, 59 guinea pigs were employed and we used compound 48/80 to deplete mast cells, cromolyn sodium to stabilize mast cells, MK-886 to inhibit leukotriene synthesis, pyrilamine to antagonize histamine H 1 receptor, methysergide to antagonize serotonin receptor, and indomethacin to inhibit cyclooxygenase. In the second experiment, 56 compound 48/80-pretreated animals were divided into two parts; the first one was used to test the role of exogenous leukotriene (LT) C 4 , while the second one to test the role of exogenous histamine in CA-induced cough. Each animal with one of the above pretreatments was exposed sequentially to saline (baseline) and CA (0.6 M) aerosol, each for 3 min. Then, cough was recorded for 12 min using a barometric body plethysmograph. In the third experiment, the activation of mast cells upon CA inhalation was investigated by determining arterial plasma histamine concentration in 17 animals. Exposure to CA induced a marked increase in cough number. Compound 48/80, cromolyn sodium, MK-886 and pyrilamine, but not indomethacin or methysergide, significantly attenuated CA-induced cough. Injection of LTC 4 or histamine caused a significant increase in CA-induced cough in compound 48/80-pretreated animals. In addition, CA inhalation caused significant increase in plasma histamine concentration, which was blocked by compound 48/80 pretreatment. These results suggest that mast cells play an important role in CA aerosol inhalation-induced cough via perhaps mediators LTs and histamine

  11. Use of granisetron transdermal system in the prevention of chemotherapy-induced nausea and vomiting: a review

    Directory of Open Access Journals (Sweden)

    Albert Tuca

    2009-12-01

    Full Text Available Albert TucaPalliative Care Hospital Team, Palliative Care Department, Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, SpainAbstract: Until now only intravenous and oral formulations of 5HT3 receptor antagonists have been available. Recently a new formulation of a 5HT3 receptor antagonist, transdermal granisetron, has been developed, and approved by the FDA. Three phase I studies to evaluate its pharmacokinetic profile have shown that granisetron administered by a transdermal delivery system is absorbed by passive diffusion and maximal concentration is reached 48 hours after patch application. The patch of 52 cm2, which contains 34.3 mg of granisetron, releases 3.3 mg of the drug every day and maintains a stable average plasma concentration of 2.2 ng/mL over 6 days, similar to levels obtained with 2 mg of oral granisetron, administered every day during the same period of time. Two randomized as yet unpublished clinical trials (phase II/III have been conducted to evaluate the antiemetic efficacy of transdermal granisetron in chemotherapy-induced nausea and vomiting, in patients receiving moderately and highly emetogenic chemotherapy, compared with 2 mg of oral granisetron. More than 800 cancer patients were included in the trials. The rate of complete control of acute emesis was 49% for the phase II trial and 60% for the phase III trial. Neither trial showed a statistically significant difference between transdermal and oral granisetron. The control of delayed emesis was observed in 46% of patients, and there were no statistically significant differences between transdermal and oral granisetron. The most common adverse effects in both trials were constipation (<7% and headache (<1%; there were no statistically significant differences between transdermal and oral granisetron. These data show that transdermal granisetron is effective and safe in controlling acute emesis induced by chemotherapy with both moderate and high

  12. Anti-inflammatory activity of 6-hydroxy-2,7-dimethoxy-1,4-henanthraquinone from tuberous roots of yam (Dioscorea batatas) through inhibition of prostaglandin D₂ and leukotriene C₄ production in mouse bone marrow-derived mast cells.

    Science.gov (United States)

    Jin, Meihua; Lu, Yue; Yang, Ju Hye; Jo, Tae Hyung; Park, Young In; Lee, Chong-Kil; Park, Sang-Jo; Son, Kun Ho; Chang, Hyeun Wook

    2011-09-01

    6-Hydroxy-2,7-dimethoxy-1,4-phenanthraquinone (PAQ) isolated from the tuberous roots of Yam (Dioscorea batatas) inhibited cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) dependent prostaglandin D(2) (PGD(2)) generation in mouse bone marrow-derived mast cells in a concentration-dependent manner with IC(50) values of 0.08 μM and 0.27 μM, respectively. In the Western blotting with specific anti-COX-2 antibodies, the decrease of the quantity of PGD(2) was accompanied by a decrease in the COX-2 protein level. But PAQ did not affect COX-1 protein level. In addition, this compound inhibited 5-lipoxygenase (5-LOX) dependent production of leukotriene C(4) in a dose-dependent manner, with an IC(50) of 0.032 μM. These results demonstrate that PAQ has a dual COX-2/5-LOX inhibitory activity. This compound also inhibited the degranulation reaction in a dose-dependent manner with an IC(50) of 2.7 μM. Thus, these results suggest that PAQ may be useful in regulating mast cell-mediated inflammatory diseases.

  13. [A case of mFOLFOX6-induced lactic acidosis in a patient with colon cancer].

    Science.gov (United States)

    Ito, Atene; Kawamoto, Kazuyuki; Park, Taebun; Ito, Tadashi

    2014-11-01

    Leucovorin calcium, 5-fluorouracil, and oxaliplatin (FOLFOX) therapy is a standard chemotherapy regimen used to treat colorectal cancer. Peripheral nerve disorder and myelosuppression are frequently reported treatment-related adverse events. With modified FOLFOX6 (mFOLFOX6) therapy, adverse events of an altered mental state with reversible posterior leukoencephalopathy and hypoammonemia have been reported, while lactic acidosis is uncommon. We describe a case of mFOLFOX6 - induced lactic acidosis in a 64-year-old man with colorectal cancer who underwent pelvic exenteration following chemotherapy. Postoperative histopathological analysis revealed residual cancer. Following the commencement of mFOLFOX6 therapy, the patient experienced emesis, hiccupping, and an altered mental state. Laboratory testing revealed only severe lactic acidosis, while diagnostic imaging was unrevealing. All symptoms quickly improved upon the administration of intravenous infusion of sodium bicarbonate.

  14. Recent advances in pharmacotherapy of chemotherapy-induced nausea and vomiting

    Directory of Open Access Journals (Sweden)

    Prasan R Bhandari

    2012-01-01

    Full Text Available Nausea and vomiting remain among the most feared side effects of chemotherapy for cancer patients. Significant progress has been made in the last 15 years in developing more effective and better-tolerated measures to minimize chemotherapy-induced nausea and vomiting (CINV. During the 1990s, the selective 5-hydroxytryptamine receptor antagonists were first introduced for the treatment of CINV, and resulted in more effective and better tolerated treatment of CINV. Despite recent progress, however, a significant number of patients still develop CINV, particularly during the 2-5-day period (delayed emesis following chemotherapy. There is evidence that this may be an underappreciated problem on the part of some caregivers. Recently, two new antiemetics, aprepitant, the first member of the neurokinin-1 antagonists, and palonosetron, a second-generation 5-hydroxytryptamine receptor antagonist, received regulatory approval in the U.S. Both represent useful additions to the therapeutic armamentarium for the management of CINV.

  15. Recent advances in pharmacotherapy of chemotherapy-induced nausea and vomiting.

    Directory of Open Access Journals (Sweden)

    Prasan R Bhandari

    2012-01-01

    Full Text Available Nausea and vomiting remain among the most feared side effects of chemotherapy for cancer patients. Significant progress has been made in the last 15 years in developing more effective and better-tolerated measures to minimize chemotherapy-induced nausea and vomiting (CINV. During the 1990s, the selective 5-hydroxytryptamine receptor antagonists were first introduced for the treatment of CINV, and resulted in more effective and better tolerated treatment of CINV. Despite recent progress, however, a significant number of patients still develop CINV, particularly during the 2-5-day period (delayed emesis following chemotherapy. There is evidence that this may be an underappreciated problem on the part of some caregivers. Recently, two new antiemetics, aprepitant, the first member of the neurokinin-1 antagonists, and palonosetron, a second-generation 5-hydroxytryptamine receptor antagonist, received regulatory approval in the U.S. Both represent useful additions to the therapeutic armamentarium for the management of CINV.

  16. Pesticide-induced quadriplegia in a 55-year-old woman.

    Science.gov (United States)

    Beavers, Charles T; Parker, Joseph J; Flinchum, Dane A; Weakley-Jones, Barbara A; Jortani, Saeed A

    2014-12-01

    Acephate is a commercial organophosphate pesticide formerly used in households and now used primarily for agriculture. Poisoning symptoms include salivation, lacrimation, urination, defecation, gastrointestinal illness, and emesis. In addition to these classic symptoms, neurodegeneration can result from increased and continued exposure of organophosphates. This 55-year-old woman presented with organophosphate-induced delayed neuropathy in the form of quadriplegia due to the commonly used pesticide acephate. She was exposed to this pesticide through multiple sprayings in her work office with underrecognized poisoning symptoms. She presented to her primary care physician with neuropathic pain and paralysis in her arm following the sprayings and eventual complete paralysis. The patient lived for 2 years following her toxic exposure and quadriplegia. A complete autopsy after her death confirmed a transverse myelitis in her spinal cord. We conclude that in susceptible individuals, acephate in excessive amounts can produce severe delayed neurotoxicity as demonstrated in animal studies.

  17. Use of granisetron transdermal system in the prevention of chemotherapy-induced nausea and vomiting: a review

    International Nuclear Information System (INIS)

    Tuca, Albert

    2009-01-01

    Until now only intravenous and oral formulations of 5HT 3 receptor antagonists have been available. Recently a new formulation of a 5HT 3 receptor antagonist, transdermal granisetron, has been developed, and approved by the FDA. Three phase I studies to evaluate its pharmacokinetic profile have shown that granisetron administered by a transdermal delivery system is absorbed by passive diffusion and maximal concentration is reached 48 hours after patch application. The patch of 52 cm 2 , which contains 34.3 mg of granisetron, releases 3.3 mg of the drug every day and maintains a stable average plasma concentration of 2.2 ng/mL over 6 days, similar to levels obtained with 2 mg of oral granisetron, administered every day during the same period of time. Two randomized as yet unpublished clinical trials (phase II/III) have been conducted to evaluate the antiemetic efficacy of transdermal granisetron in chemotherapy-induced nausea and vomiting, in patients receiving moderately and highly emetogenic chemotherapy, compared with 2 mg of oral granisetron. More than 800 cancer patients were included in the trials. The rate of complete control of acute emesis was 49% for the phase II trial and 60% for the phase III trial. Neither trial showed a statistically significant difference between transdermal and oral granisetron. The control of delayed emesis was observed in 46% of patients, and there were no statistically significant differences between transdermal and oral granisetron. The most common adverse effects in both trials were constipation (<7%) and headache (<1%); there were no statistically significant differences between transdermal and oral granisetron. These data show that transdermal granisetron is effective and safe in controlling acute emesis induced by chemotherapy with both moderate and high emetogenic potential. Efficacy and safety of transdermal granisetron are fully comparable with that of oral granisetron. More clinical trials using regimens of 2 or 3 drugs

  18. Olanzapine is effective for refractory chemotherapy-induced nausea and vomiting irrespective of chemotherapy emetogenicity.

    Science.gov (United States)

    Vig, Sierra; Seibert, Laurel; Green, Myke R

    2014-01-01

    The role of olanzapine added to a dopamine antagonist and benzodiazepine for the treatment of refractory chemotherapy-induced nausea and vomiting (CINV) is incompletely characterized in all levels of chemotherapy emetogenicity. This retrospective study evaluated the efficacy of the addition of olanzapine in adults experiencing refractory CINV stratified by chemotherapy emetogenicity. Thirty-three adults who experienced CINV refractory to guideline-recommended prophylaxis and breakthrough antiemetics (dopamine antagonists and benzodiazepines) and received at least one dose of olanzapine 5-10 mg per os were evaluated. Failure was defined as >5 emesis events in 24 h or more than 10 cumulative doses of rescue antiemetics following first olanzapine dose per treatment cycle. Post hoc analyses investigated variables impacting olanzapine efficacy. The addition of olanzapine demonstrated an overall success rate of 70 %. This success rate did not differ between chemotherapy regimens of high versus low-to-moderate emetogenicity (p = 0.79), prophylaxis with serotonin antagonist plus corticosteroid and aprepitant versus serotonin antagonist alone (p = 0.77), or age over 50 versus ≤50 years (p > 0.99). A trend toward greater benefit was seen in women (p = 0.08). The addition of olanzapine to a dopamine antagonist and benzodiazepine demonstrated high efficacy rates for refractory CINV irrespective of chemotherapy emetogenicity. The high success rates among all groups suggests that incomplete resolution of CINV with prophylactic serotonin antagonists and breakthrough dopamine antagonists plus benzodiazepine may benefit from the addition of olanzapine regardless of gender, degree of chemotherapy emetogenicity, number of prophylactic antiemetics, or age. The trend toward greater control of emesis in women merits further investigation.

  19. Reviewing current and emerging antiemetics for chemotherapy-induced nausea and vomiting prophylaxis.

    Science.gov (United States)

    Natale, James J

    2015-01-01

    This review provides background information on chemotherapy-induced nausea and vomiting (CINV) classification and pathophysiology and reviews various antiemetic agents for CINV prophylaxis, including corticosteroids, serotonin receptor antagonists (5-HT3 RAs), tachykinin NK1 receptor antagonists (NK1 RAs), and olanzapine. Other less commonly used agents are briefly discussed. Practical considerations are reviewed as well, including emetogenicity of chemotherapeutic regimens, patient-specific risk factors for CINV, principles of CINV management, health economics outcome research, and quality of life. Available data on the newly FDA-approved antiemetic combination netupitant/palonosetron (NEPA) is also reviewed. Prevention of CINV is an important goal in managing patients with cancer and is especially difficult with respect to nausea and delayed CINV. Corticosteroids are a mainstay of CINV prophylaxis and are usually given in combination with other therapies. The 5-HT3 RA palonosetron has shown increased efficacy over other agents in the same class for prevention of delayed emesis with moderately emetogenic chemotherapy and NK1 RAs improve emesis prevention in combination with 5-HT3 RAs and dexamethasone. Olanzapine has shown efficacy for CINV prophylaxis and the treatment of breakthrough CINV. The new combination therapy, NEPA, has been shown to be efficacious for the prevention of acute, delayed, and overall CINV. Risk factors that have been identified for CINV include gender, age, and alcohol intake. It is important to assess the emetogenicity of chemotherapy regimens as well as the potential impact of patient risk factors in order to provide adequate prophylaxis. Acute and delayed CINV are severe, burdensome side effects of chemotherapy; however, new data on prevention and the discovery of new agents can further improve CINV control.

  20. Diclocor is superior to diclofenac sodium and quercetin in normalizing biochemical parameters in rats with collagen-induced osteoarthritis.

    Science.gov (United States)

    Zupanets, I A; Shebeko, S K; Popov, O S; Shalamay, A S

    2016-02-01

    The aim of the present study was to investigate anti-inflammatory activity of Diclocor in the setting of collagen-induced osteoarthritis in rats in comparison with its active monocomponents-diclofenac sodium and quercetin. The study was conducted on the model of collagen-induced osteoarthritis and included measurement of sialic acids, glycoproteins, C-reactive protein, prostaglandin E2, 6-keto-prostaglandin F1α, thromboxane B2, and leukotriene B4. Lastly, morphologic study with morphometry was also performed. Diclocor is superior to quercetin and diclofenac sodium by the degree of pharmacological effect on some of the studied parameters. The differences between the values were statistically significant. Diclocor is a promising corrector of inflammatory and destructive joint diseases. Owing to the presence of both diclofenac sodium and quercetin in its composition, Diclocor exhibits a complex mechanism of anti-inflammatory action affecting cyclooxygenase and lipoxygenase ways of arachidonic acid biotransformation.

  1. [Iatrogenic bronchial obstruction: study of 4 atopic children with bronchial obstruction induced by acetyl salicylic acid].

    Science.gov (United States)

    De Luca, L; Vuillemier, P L; Principe, A M; Petrillo, T

    1986-01-01

    The authors have studied the modification of the spirometric parameters in four atopic children, during nonallergic diet, after administration of ASA (400 mg). The examination of the respiratory functionality has showed a fall of parameters starting four hours after the challenge and with an increase of respiratory resistance. This bronchospastic reaction persisted for about eighteen hours to diminish 24 h. after administration of 400 mg of ASA. The study of spirometric values has showed a remarkable fall of MMEF, sign of small airways obstruction, but also of FEV1-CV for the involvement of the higher airways. The authors attribute the reaction to the metabolites of arachidonic acid (Leukotrienes) and to their different receptor site on the bronchial mucous membrane target cells. The authors conclude showing the gravity of injury that will induce imprudent administration of ASA in hypersensitive subject.

  2. Increased Levels of Txa₂ Induced by Dengue Virus Infection in IgM Positive Individuals Is Related to the Mild Symptoms of Dengue.

    Science.gov (United States)

    Oliveira, Eneida S; Colombarolli, Stella G; Nascimento, Camila S; Batista, Izabella C A; Ferreira, Jorge G G; Alvarenga, Daniele L R; de Sousa, Laís O B; Assis, Rafael R; Rocha, Marcele N; Alves, Érica A R; Calzavara-Silva, Carlos E

    2018-02-28

    The inflammatory process plays a major role in the prognosis of dengue. In this context, the eicosanoids may have considerable influence on the regulation of the Dengue virus -induced inflammatory process. To quantify the molecules involved in the cyclooxygenase and lipoxygenase pathways during Dengue virus infection, plasma levels of thromboxane A2, prostaglandin E2 and leukotriene B4; mRNA levels of thromboxane A2 synthase, prostaglandin E2 synthase, leukotriene A4 hydrolase, cyclooxygenase-2 and 5-lipoxygenase; and the levels of lipid bodies in peripheral blood leukocytes collected from IgM-positive and IgM-negative volunteers with mild dengue, and non-infected volunteers, were evaluated. Dengue virus infection increases the levels of thromboxane A2 in IgM-positive individuals as well as the amount of lipid bodies in monocytes in IgM-negative individuals. We suggest that increased levels of thromboxane A2 in IgM-positive individuals plays a protective role against the development of severe symptoms of dengue, such as vascular leakage.

  3. Increased Levels of Txa2 Induced by Dengue Virus Infection in IgM Positive Individuals Is Related to the Mild Symptoms of Dengue

    Science.gov (United States)

    Oliveira, Eneida S.; Colombarolli, Stella G.; Nascimento, Camila S.; Batista, Izabella C. A.; Ferreira, Jorge G. G.; Alvarenga, Daniele L. R.; de Sousa, Laís O. B.; Assis, Rafael R.; Rocha, Marcele N.; Alves, Érica A. R.; Calzavara-Silva, Carlos E.

    2018-01-01

    The inflammatory process plays a major role in the prognosis of dengue. In this context, the eicosanoids may have considerable influence on the regulation of the Dengue virus-induced inflammatory process. To quantify the molecules involved in the cyclooxygenase and lipoxygenase pathways during Dengue virus infection, plasma levels of thromboxane A2, prostaglandin E2 and leukotriene B4; mRNA levels of thromboxane A2 synthase, prostaglandin E2 synthase, leukotriene A4 hydrolase, cyclooxygenase-2 and 5-lipoxygenase; and the levels of lipid bodies in peripheral blood leukocytes collected from IgM-positive and IgM-negative volunteers with mild dengue, and non-infected volunteers, were evaluated. Dengue virus infection increases the levels of thromboxane A2 in IgM-positive individuals as well as the amount of lipid bodies in monocytes in IgM-negative individuals. We suggest that increased levels of thromboxane A2 in IgM-positive individuals plays a protective role against the development of severe symptoms of dengue, such as vascular leakage. PMID:29495587

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

    Science.gov (United States)

    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 (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.

  5. The influence of domperidone, metoclopramide and sulpiride on early-stage radioemesis

    International Nuclear Information System (INIS)

    Yuan Lizhen; Song Ling; Ge Guixiu

    1990-01-01

    Domperidone, metoclopramide and sulpiride were examined for their protective and therapeutic effects against the emesis within 6 hours after 7 Gy 60 Co γ-irradiation in 40 dogs. The incidence of emesis occurred in control group was 82% (9/11). All the dogs protected with domperidone could prevent radiation-induced emesis. The metoclopramide could eliminate radiation induced emesis in three of five dogs too. In other four groups (domperidone therapeutic, metoclopramide therapeutic, sulpiride protective or therapeutic), the incidence of emesis was the same as in control, but the episodes of vomiting and duration between the onset and last episodes were decreased

  6. Slow-release granisetron (APF530) versus palonosetron for chemotherapy-induced nausea/vomiting: analysis by American Society of Clinical Oncology emetogenicity criteria.

    Science.gov (United States)

    Raftopoulos, Harry; Boccia, Ralph; Cooper, William; O'Boyle, Erin; Gralla, Richard J

    2015-09-01

    APF530 is a novel sustained-release formulation of granisetron. In a Phase III trial, APF530 500 mg was noninferior to palonosetron 0.25 mg in preventing acute chemotherapy-induced nausea and vomiting (CINV) after moderately (MEC) or highly emetogenic chemotherapy (HEC) and delayed CINV after MEC, but not superior in preventing delayed CINV after HEC. Emetogenicity was classified by Hesketh criteria; this reanalysis uses newer American Society of Clinical Oncology criteria. Complete responses (no emesis or rescue medication) after cycle one were reanalyzed after reclassification of MEC and HEC by American Society of Clinical Oncology criteria. APF530 maintained noninferiority to palonosetron. Single-dose APF530 is a promising alternative to palonosetron for preventing acute and delayed CINV after MEC or HEC. The Clinicaltrials.gov identifier for this study is NCT00343460.

  7. Critical Review of Selected Components of RIPD (Radiation-Induced Performance Decrement)

    Science.gov (United States)

    2012-12-01

    The response of the emetic centers elicits the signs and symptoms of UG distress. The levels of A are converted to a measure of severity of emesis ...Mean n Mean n developmen ms as emes cally and ph y need an a emesis bec antifying it i odel f cell loss in rotracted rad he lethal/po n, the prolif...210. Andrews, P.L.R., and Horn C.C., 2006. “Signals for nausea and emesis : Implications for models of upper gastrointestinal diseases,” Auton

  8. Multifactorial Modulation of Food-Induced Anaphylaxis

    Directory of Open Access Journals (Sweden)

    Sara Benedé

    2017-05-01

    Full Text Available Prevalence of food-induced anaphylaxis increases progressively and occurs in an unpredictable manner, seriously affecting the quality of life of patients. Intrinsic factors including age, physiological, and genetic features of the patient as well as extrinsic factors such as the intake of drugs and exposure to environmental agents modulate this disorder. It has been proven that diseases, such as mastocytosis, defects in HLA, or filaggrin genes, increase the risk of severe allergic episodes. Certain allergen families such as storage proteins, lipid transfer proteins, or parvalbumins have also been linked to anaphylaxis. Environmental factors such as inhaled allergens or sensitization through the skin can exacerbate or trigger acute anaphylaxis. Moreover, the effect of dietary habits such as the early introduction of certain foods in the diet, and the advantage of the breastfeeding remain as yet unresolved. Interaction of allergens with the intestinal cell barrier together with a set of effector cells represents the primary pathways of food-induced anaphylaxis. After an antigen cross-links the IgEs on the membrane of effector cells, a complex intracellular signaling cascade is initiated, which leads cells to release preformed mediators stored in their granules that are responsible for the acute symptoms of anaphylaxis. Afterward, they can also rapidly synthesize lipid compounds such as prostaglandins or leukotrienes. Cytokines or chemokines are also released, leading to the recruitment and activation of immune cells in the inflammatory microenvironment. Multiple factors that affect food-induced anaphylaxis are discussed in this review, paying special attention to dietary habits and environmental and genetic conditions.

  9. Tropisetron attenuates cisplatin-induced nephrotoxicity in mice.

    Science.gov (United States)

    Zirak, Mohammad Reza; Rahimian, Reza; Ghazi-Khansari, Mahmoud; Abbasi, Ata; Razmi, Ali; Mehr, Shahram Ejtemaei; Mousavizadeh, Kazem; Dehpour, Ahmad Reza

    2014-09-05

    Nephrotoxicity is one of the most important complications of cisplatin, a potent chemotherapeutic agent used in the treatment of various malignancies. 5-HT3 antagonists are widely used to counteract chemotherapy-induced emesis and new studies reveal that they poses notable anti-inflammatory properties. In current study, we investigated the effects of 5-HT3 antagonists on cisplatin induced nephrotoxicity in mice. To identify the underlying mechanism of renal protection by tropisetron, we investigated the probable involvement of alpha7 nicotinic acetylcholine receptor (α7nAChR). A single injection of cisplatin (20mg/kg; i.p) induced nephrotoxicity, 5-HT3 antagonists (tropisetron, granisetron and ondansetron,) were given twice daily for 3 day (3mg/kg; i.p). Finally animals were euthanized and blood sample was collected to measure urea and creatinin level. Also kidneys were removed for histopathological examination and biochemical measurements including glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) activity, inducible nitric oxide synthase (iNOS) expression and inflammatory cytokines. Tropisetron decreased the expression of inflammatory molecules including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and iNOS and improved histopathological damage and renal dysfunction. However other 5-HT3 antagonists, granisetron or ondansetron do not have any elicit effects on biochemical markers and histological damages. Since methyllycaconitine, antagonist of α7nAChR, was unable to reverse the beneficial effect of tropisetron, we concluded that this effect of tropisetron is not mediated by α7nAChR.Our results showed that tropisetron treatment markedly ameliorated the experimental cisplatin induced-nephrotoxicity and this effect might be 5-HT3 receptor and α7nAChR independent. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Leukotriene modifiers in pediatric asthma management

    DEFF Research Database (Denmark)

    Bisgaard, H

    2001-01-01

    -acting beta-agonists as complementary treatment to inhaled corticosteroids in pediatric asthma management because they provide bronchodilation and bronchoprotection without development of tolerance, and complement the antiinflammatory activity unchecked by steroids. In addition, the Cys-LTRA montelukast has...

  11. Are leukotriene inhibitors useful for bronchiolitis?

    Directory of Open Access Journals (Sweden)

    : Fernanda Pérez-Gutiérrez

    2016-12-01

    Full Text Available Resumen La bronquiolitis es una patología prevalente en niños menores de dos años que conlleva importante morbimortalidad. No obstante, aún existe controversia sobre el manejo más adecuado. Se ha planteado el uso de los inhibidores de leucotrienos como opción terapéutica, sin embargo no está clara su real utilidad clínica. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en múltiples bases de datos, identificamos dos revisiones sistemáticas que en conjunto incluyen seis estudios aleatorizados controlados pertinentes a la pregunta. Extrajimos los datos, realizamos un metanálisis y preparamos tablas de resumen de los resultados utilizando el método GRADE. Concluimos que los inhibidores de leucotrienos podrían no disminuir la mortalidad en pacientes con bronquiolitis y no está claro si disminuyen los días de hospitalización. Podrían disminuir las recurrencias de cuadros sibilantes en pacientes con bronquiolitis, pero la certeza de la evidencia es baja y, por otra parte, aumentan los efectos adversos.

  12. The prevention and treatment of radiotherapy induced nausea and vomiting

    International Nuclear Information System (INIS)

    Van Zyl, A.J.

    1992-11-01

    Nausea and vomiting are side-effects that are associated with chemo- and radiotherapy. A single-blind study to compare the efficacy and safety of intravenous granisetron (G) with metoclopramide (M) plus dexamethasone (D) in the prophylaxis and control of nausea and emesis in patients undergoing hemi-body irradiation (HBI) was performed. G (3 mg) or M (20 mg) plus D (12 mg) were given intravenously, thirty minutes prior to the start of radiotherapy. Patients were monitored for nausea, vomiting and side-effects. Thirty-five patients were treated, 28 men and 7 women. A total of 21 (60%) patients did not vomit during the first 24 hours after the start of radiotherapy. Both G and M plus D offer safe and effective anti-emetic regimes for the prophylaxis and control of radiotherapy induced nausea and vomiting. However, granisetron was found to be more effective than metoclopramide plus dexamethasone in preventing nausea and vomiting. 101 refs., 40 tabs., 8 figs

  13. Neutrophil predominance in induced sputum from asthmatic patients: Therapeutic implications and role of clara cell 16-KD protein

    Directory of Open Access Journals (Sweden)

    Elisa M. Uribe Echevarría

    2011-08-01

    Full Text Available Eosinophil is considered to be a main protagonist in asthma; however, often discordances between clinical manifestations and response to treatment are observed. We aimed to determine the occurrence of neutrophil predominance in asthma and to identify its characteristics on the basis of clinical-functional features, induced sputum cellular pattern and soluble molecules, to guide the appropriated anti-inflammatory therapy. A total of 41 patients were included in randomized groups: 21-40 year-old, with stable mild-to-severe asthma, steroid-naïve and non-smokers. An induced sputum sample was obtained under basal conditions, a second one after treatment with budesonide (400 µg b.i.d. or montelukast (10 mg/d for six weeks, and a final one after a 4-week washout period. By cytospin we evaluated eosinophil (EP or neutrophil predominance (NP, and in supernatant we determined LTE4, and CC16. Peak expiratory flow variability (PEFV was measured. A total of 23/41 patients corresponded to EP and 18/41 patients to NP. The PEFV was higher in EP than in NP. LTE4 was higher with NP than with EP. No difference was found for CC16. Montelukast reduced the predominant cell in both subsets, whereas budesonide only reduced eosinophils in EP. Budesonide and montelukast reduced PEFV in EP but not in NP. Considering the total treated-samples in each subset, CC16 level increased significantly in EP. In conclusion: a NP subset of asthmatic patients was identified. These patients show a lower bronchial lability; the leukotriene pathway is involved which responds to anti-leukotriene treatment. This phenotype shows a poor recovery of CC16 level after treatment.

  14. Frondanol, a Nutraceutical Extract from Cucumaria frondosa, Attenuates Colonic Inflammation in a DSS-Induced Colitis Model in Mice

    Directory of Open Access Journals (Sweden)

    Sandeep B. Subramanya

    2018-04-01

    Full Text Available Frondanol is a nutraceutical lipid extract of the intestine of the edible Atlantic sea cucumber, Cucumaria frondosa, with potent anti-inflammatory effects. In the current study, we investigated Frondanol as a putative anti-inflammatory compound in an experimental model of colonic inflammation. C57BL/6J male black mice (C57BL/6J were given 3% dextran sodium sulfate (DSS in drinking water for 7 days to induce colitis. The colitis group received oral Frondanol (100 mg/kg body weight/per day by gavage and were compared with a control group and the DSS group. Disease activity index (DAI and colon histology were scored for macroscopic and microscopic changes. Colonic tissue length, myeloperoxidase (MPO concentration, neutrophil and macrophage marker mRNA, pro-inflammatory cytokine proteins, and their respective mRNAs were measured using ELISA and real-time RT-PCR. The tissue content of leukotriene B4 (LTB4 was also measured using ELISA. Frondanol significantly decreased the DAI and reduced the inflammation-associated changes in colon length as well as macroscopic and microscopic architecture of the colon. Changes in tissue MPO concentrations, neutrophil and macrophage mRNA expression (F4/80 and MIP-2, and pro-inflammatory cytokine content (IL-1β, IL-6 and TNF-α both at the protein and mRNA level were significantly reduced by Frondanol. The increase in content of the pro-inflammatory mediator leukotriene B4 (LTB4 induced by DSS was also significantly inhibited by Frondanol. It was thus found that Frondanol supplementation attenuates colon inflammation through its potent anti-inflammatory activity.

  15. Food protein induced enterocolitis syndrome caused by rice beverage.

    Science.gov (United States)

    Caminiti, Lucia; Salzano, Giuseppina; Crisafulli, Giuseppe; Porcaro, Federica; Pajno, Giovanni Battista

    2013-05-14

    Food protein-induced enterocolitis syndrome (FPIES) is an uncommon and potentially severe non IgE-mediated gastrointestinal food allergy. It is usually caused by cow's milk or soy proteins, but may also be triggered by ingestion of solid foods. The diagnosis is made on the basis of clinical history and symptoms. Management of acute phase requires fluid resuscitation and intravenous steroids administration, but avoidance of offending foods is the only effective therapeutic option.Infant with FPIES presented to our emergency department with vomiting, watery stools, hypothension and metabolic acidosis after ingestion of rice beverage. Intravenous fluids and steroids were administered with good clinical response. Subsequently, a double blind placebo control food challenge (DBPCFC) was performed using rice beverage and hydrolyzed formula (eHF) as placebo. The "rice based formula" induced emesis, diarrhoea and lethargy. Laboratory investigations reveal an increase of absolute count of neutrophils and the presence of faecal eosinophils. The patient was treated with both intravenous hydration and steroids. According to Powell criteria, oral food challenge was considered positive and diagnosis of FPIES induced by rice beverage was made. Patient was discharged at home with the indication to avoid rice and any rice beverage as well as to reintroduce hydrolyzed formula. A case of FPIES induced by rice beverage has never been reported. The present case clearly shows that also beverage containing rice proteins can be responsible of FPIES. For this reason, the use of rice beverage as cow's milk substitute for the treatment of non IgE-mediated food allergy should be avoided.

  16. 5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality

    Directory of Open Access Journals (Sweden)

    Miriam S. N. Hohmann

    2013-01-01

    Full Text Available 5-Lipoxygenase (5-LO converts arachidonic acid into leukotrienes (LTs and is involved in inflammation. At present, the participation of 5-LO in acetaminophen (APAP-induced hepatotoxicity and liver damage has not been addressed. 5-LO deficient (5-LO-/- mice and background wild type mice were challenged with APAP (0.3–6 g/kg or saline. The lethality, liver damage, neutrophil and macrophage recruitment, LTB4, cytokine production, and oxidative stress were assessed. APAP induced a dose-dependent mortality, and the dose of 3 g/kg was selected for next experiments. APAP induced LTB4 production in the liver, the primary target organ in APAP toxicity. Histopathological analysis revealed that 5-LO-/- mice presented reduced APAP-induced liver necrosis and inflammation compared with WT mice. APAP-induced lethality, increase of plasma levels of aspartate aminotransferase and alanine aminotransferase, liver cytokine (IL-1β, TNF-α, IFN-γ, and IL-10, superoxide anion, and thiobarbituric acid reactive substances production, myeloperoxidase and N-acetyl-β-D-glucosaminidase activity, Nrf2 and gp91phox mRNA expression, and decrease of reduced glutathione and antioxidant capacity measured by 2,2′-azinobis(3-ethylbenzothiazoline 6-sulfonate assay were prevented in 5-LO-/- mice compared to WT mice. Therefore, 5-LO deficiency resulted in reduced mortality due to reduced liver inflammatory and oxidative damage, suggesting 5-LO is a promising target to reduce APAP-induced lethality and liver inflammatory/oxidative damage.

  17. Antiemetic and Myeloprotective Effects of Rhus verniciflua Stoke in a Cisplatin-Induced Rat Model

    Directory of Open Access Journals (Sweden)

    Hyo-Seon Kim

    2017-01-01

    Full Text Available Rhus verniciflua Stoke has been commonly used in traditional medicine to treat gastrointestinal (GI dysfunction diseases. In order to investigate pharmacological properties of Rhus verniciflua Stoke water extract (RVX on cisplatin-induced amnesia, RVX (0, 25, 50, or 100 mg/kg was orally administrated for five consecutive days after a single intraperitoneal injection of cisplatin (6 mg/kg to SD rat. Cisplatin injection significantly increased the kaolin intake (emesis but reduced the normal diet intake (anorexia whereas the RVX treatment significantly improved these abnormal diet behaviors at both the acute and delayed phase. The serotonin concentration and the related gene expressions (5-HT3 receptors and SERT in small intestine tissue were abnormally altered by cisplatin injection, which were significantly attenuated by the RVX treatment. Histological findings of gastrointestinal tracts, as well as the proteins level of proinflammatory cytokines (TNF-α, IL-6, and IL-1β, revealed the beneficial effect of RVX on cisplatin-induced gastrointestinal inflammation. In addition, RVX significantly improved cisplatin-induced myelosuppression, as evidenced by the observation of leukopenia and by histological examinations in bone marrow. Our findings collectively indicated Rhus verniciflua Stoke improved the resistance of rats to chemotherapy-related adverse effects in the gastrointestinal track and bone marrow.

  18. Characterization of cutaneous vascular permeability induced by platelet-activating factor in guinea pigs and rats and its inhibition by a platelet-activating factor receptor antagonist

    International Nuclear Information System (INIS)

    Hwang, S.B.; Li, C.L.; Lam, M.H.; Shen, T.Y.

    1985-01-01

    Mechanisms of platelet-activating factor (PAF)-induced increases of cutaneous vascular permeability in guinea pigs and in rats were further explored. PAF so far is the most potent vasoactive mediator, being more than 1000-fold more potent than histamine and bradykinin in both species. In guinea pigs, there is a time delay of 5 to 10 minutes before PAF action, whereas, in the rat, the increased vasopermeability occurs immediately following the intradermal PAF injection. Relative vasoactive potencies of PAF and several structure-related analogues in both species correlate very well with their relative inhibition of the binding of 3 H-PAF to specific receptor sites on isolated rabbit platelet plasma membranes and their aggregatory abilities of rabbit platelets. Furthermore, the PAF-induced cutaneous vascular permeability is inhibitable by a competitive specific PAF receptor antagonist, kadsurenone, suggesting that binding of PAF to its specific receptor site is the first step to initiate its action of increased cutaneous vascular permeability. Several pure cyclooxygenase inhibitors, including indomethacin, diflunisal, and flurbiprofen, and the dual cyclooxygenase/lipoxygenase inhibitor, BW755C, but not the histamine antagonists, inhibit the PAF-induced vasopermeability in guinea pigs. The inhibition by indomethacin or BW755C can be fully reversed by coinjection intradermally with PAF and prostaglandin E1 but not leukotriene B4. Also, prostaglandin E1 but not leukotriene B4 enhances the guinea pig in vivo response to PAF in this model. However, in rats, none of the cyclooxygenase inhibitors, histamine antagonists, or BW755C inhibit the PAF effect of cutaneous phenomena

  19. Additive effect of rikkunshito, an herbal medicine, on chemotherapy-induced nausea, vomiting, and anorexia in uterine cervical or corpus cancer patients treated with cisplatin and paclitaxel: results of a randomized phase II study (JORTC KMP-02).

    Science.gov (United States)

    Ohnishi, Shunsuke; Watari, Hidemichi; Kanno, Maki; Ohba, Yoko; Takeuchi, Satoshi; Miyaji, Tempei; Oyamada, Shunsuke; Nomura, Eiji; Kato, Hidenori; Sugiyama, Toru; Asaka, Masahiro; Sakuragi, Noriaki; Yamaguchi, Takuhiro; Uezono, Yasuhito; Iwase, Satoru

    2017-09-01

    Rikkunshito, an herbal medicine, is widely prescribed in Japan for the treatment of anorexia and functional dyspepsia, and has been reported to recover reductions in food intake caused by cisplatin. We investigated whether rikkunshito could improve chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients treated with cisplatin. Patients with uterine cervical or corpus cancer who were to receive cisplatin (50 mg/m² day 1) and paclitaxel (135 mg/m² day 0) as first-line chemotherapy were randomly assigned to the rikkunshito group receiving oral administration on days 0-13 with standard antiemetics, or the control group receiving antiemetics only. The primary endpoint was the rate of complete control (CC: no emesis, no rescue medication, and no significant nausea) in the overall phase (0-120 hours). Two-tailed panorexia. Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

  20. Aprepitant plus granisetron and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients with gastric cancer treated with S-1 plus cisplatin.

    Science.gov (United States)

    Oyama, Katsunobu; Fushida, Sachio; Kaji, Masahide; Takeda, Toshiya; Kinami, Shinichi; Hirono, Yasuo; Yoshimoto, Katsuhiro; Yabushita, Kazuhisa; Hirosawa, Hisashi; Takai, Yuki; Nakano, Tatsuo; Kimura, Hironobu; Yasui, Toshiaki; Tsuneda, Atsushi; Tsukada, Tomoya; Kinoshita, Jun; Fujimura, Takashi; Ohta, Tetsuo

    2013-11-01

    We aimed to evaluate the efficacy of a new combination antiemetic therapy comprising aprepitant, granisetron, and dexamethasone in gastric cancer patients undergoing chemotherapy with cisplatin and S-1. Gastric cancer patients scheduled to receive their first course of chemotherapy with cisplatin (60 mg/m(2)) and S-1 (80 mg/m(2)) were treated with a new combination antiemetic therapy aprepitant, granisetron, and dexamethasone on day 1; aprepitant and dexamethasone on days 2 and 3; and dexamethasone on day 4. The patients reported vomiting, nausea, use of rescue therapy, and change in the amount of diet intake, and completed the Functional Living Index-Emesis (FLIE) questionnaire. The primary endpoint was complete response (CR; no emesis and use of no rescue antiemetics) during the overall study phase (0-120 h after cisplatin administration). The secondary endpoints included complete protection (CP; CR plus no significant nausea); change in the amount of diet intake; and the impact of chemotherapy-induced nausea and vomiting (CINV) on daily life during the overall, acute (0-24 h), and delayed (24-120 h) phases. Fifty-three patients were included. CR was achieved in 88.7, 98.1, and 88.7% of patients in the overall, acute, and delayed phases, respectively. The corresponding rates of CP were 67.9, 96.2, and 67.9%. Approximately half of the patients had some degree of anorexia. FLIE results indicated that 79.5% of patients reported "minimal or no impact of CINV on daily life". Addition of aprepitant to standard antiemetic therapy was effective in gastric cancer patients undergoing treatment with cisplatin and S-1.

  1. Cost-effectiveness of an aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer in the UK

    Directory of Open Access Journals (Sweden)

    Humphreys S

    2013-08-01

    Full Text Available Samantha Humphreys,1 James Pellissier,2 Alison Jones3 1Market Access Department, Merck Sharp and Dohme Ltd, Hoddesdon, Hertfordshire, UK; 2Health Economic Statistics, Merck Research Laboratories, Upper Gwynedd, PA, USA; 3Department of Medical Oncology, University College Hospital, London, UK Purpose: Prevention of chemotherapy-induced nausea and vomiting (CINV remains an important goal for patients receiving chemotherapy. The objective of this study was to define, from the UK payer perspective, the cost-effectiveness of an antiemetic regimen using aprepitant, a selective neurokinin-1 receptor antagonist, for patients receiving chemotherapy for breast cancer. Methods: A decision-analytic model was developed to compare an aprepitant regimen (aprepitant, ondansetron, and dexamethasone with a standard UK antiemetic regimen (ondansetron, dexamethasone, and metoclopramide for expected costs and health outcomes after single-day adjuvant chemotherapy for breast cancer. The model was populated with results from patients with breast cancer participating in a randomized trial of CINV preventative therapy for cycle 1 of single-day chemotherapy. Results: During 5 days after chemotherapy, 64% of patients receiving the aprepitant regimen and 47% of those receiving the UK comparator regimen had a complete response to antiemetic therapy (no emesis and no rescue antiemetic therapy. A mean of £37.11 (78% of the cost of aprepitant was offset by reduced health care resource utilization costs. The predicted gain in quality-adjusted lifeyears (QALYs with the aprepitant regimen was 0.0048. The incremental cost effectiveness ratio (ICER with aprepitant, relative to the UK comparator, was £10,847/QALY, which is well below the threshold commonly accepted in the UK of £20,000–£30,000/QALY. Conclusion: The results of this study suggest that aprepitant is cost-effective for preventing CINV associated with chemotherapy for patients with breast cancer in the UK health

  2. Evidence for the involvement of 5-lipoxygenase products in ethanol-induced intestinal plasma protein loss

    International Nuclear Information System (INIS)

    Beck, I.T.; Boyd, A.J.; Dinda, P.K.

    1988-01-01

    In this study the authors investigated whether the products of 5-lipoxygenase (5-LO) were involved in the jejunal microvascular injury induced by intraluminal ethanol (ETH). A group of rabbits was given orally a selective inhibitor of 5-LO in two 10-mg doses, 24, and 2 h before the experiments. A jejunal segment was perfused with a control solution (control segment) and an adjacent segment with an ETH-containing solution (ETH-perfused segment). In a series of experiments, they measured 5-LO activity of the jejunal segments of both groups using the generation of leukotriene B 4 (LTB 4 ) as an index. In a second series of experiments, they determined the ETH-induced intraluminal protein loss, which was taken as a measure of mucosal microvascular damage. The ETH-induced increase in protein loss was significantly lower in the treated than in the untreated group. These findings suggest that products of 5-LO are involved in the ETH-induced jejunal microvascular injury

  3. Aprepitant, granisetron, and dexamethasone for prevention of chemotherapy-induced nausea and vomiting after high-dose melphalan in autologous transplantation for multiple myeloma: results of a randomized, placebo-controlled phase III trial.

    Science.gov (United States)

    Schmitt, Thomas; Goldschmidt, Hartmut; Neben, Kai; Freiberger, Anja; Hüsing, Johannes; Gronkowski, Martina; Thalheimer, Markus; Pelzl, Le Hang; Mikus, Gerd; Burhenne, Jürgen; Ho, Anthony D; Egerer, Gerlinde

    2014-10-20

    The optimal regimen to prevent chemotherapy-induced nausea and vomiting (CINV) for patients undergoing high-dose chemotherapy and autologous stem-cell transplantation (ASCT) is unclear. To evaluate the effect of aprepitant in addition to a standard regimen, we conducted this randomized, placebo-controlled phase III trial. Patients with multiple myeloma were randomly assigned at a one-to-one ratio to receive either aprepitant (125 mg orally on day 1 and 80 mg orally on days 2 to 4), granisetron (2 mg orally on days 1 to 4), and dexamethasone (4 mg orally on day 1 and 2 mg orally on days 2 to 3) or matching placebo, granisetron (2 mg orally on days 1 to 4), and dexamethasone (8 mg orally on day 1 and 4 mg orally on days 2 to 3). Melphalan 100 mg/m(2) was administered intravenously on days 1 to 2. ASCT was performed on day 4. The primary end point (complete response) was defined as no emesis and no rescue therapy within 120 hours of melphalan administration. Quality of life was assessed by modified Functional Living Index-Emesis (FLIE) questionnaire on days -1 and 6. Overall, 362 patients were available for the efficacy analysis (181 in each treatment arm). Significantly more patients receiving aprepitant reached the primary end point (58% v 41%; odds ratio [OR], 1.92; 95% CI, 1.23 to 3.00; P = .0042). Absence of major nausea (94% v 88%; OR, 2.37; 95% CI, 1.09 to 5.15; P = .026) and emesis (78% v 65%; OR, 1.99; 95% CI, 1.25 to 3.18; P = .0036) within 120 hours was increased by aprepitant. Mean total FLIE score (± standard deviation) was 114 ± 18 for aprepitant and 106 ± 26 for placebo (P < .001). The addition of aprepitant resulted in significantly less CINV and had a positive effect on quality of life. © 2014 by American Society of Clinical Oncology.

  4. Differential pharmacology and clinical utility of rolapitant in chemotherapy-induced nausea and vomiting

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    Rapoport BL

    2017-02-01

    Full Text Available Bernardo Leon Rapoport The Medical Oncology Centre of Rosebank, Johannesburg, South Africa Abstract: Chemotherapy-induced nausea and vomiting (CINV is a debilitating side effect of many cytotoxic chemotherapy regimens. CINV typically manifests during two well-defined time periods (acute and delayed phases. The acute phase is the first 24 hours after chemotherapy and is largely managed with 5-hydroxytryptamine 3 receptor antagonists. The delayed phase, a 5-day at-risk period during which patients are not often in direct contact with their health care provider, remains a significant unmet medical need. Neurokinin-1 (NK-1 receptor antagonists have demonstrated protection against acute and delayed CINV in patients treated with highly emetogenic chemotherapy and moderately emetogenic chemotherapy when used in combination with a 5-hydroxytryptamine 3 receptor antagonist and dexamethasone. Furthermore, recent data indicate that this protection is maintained over multiple treatment cycles. Rolapitant, a selective and long-acting NK-1 receptor antagonist, is approved as oral formulation for the prevention of delayed CINV in adults. This review discusses the differential pharmacology and clinical utility of rolapitant in preventing CINV compared with other NK-1 receptor antagonists. Keywords: antiemetics, highly emetogenic chemotherapy, moderately emetogenic chemotherapy, delayed chemotherapy-induced nausea and vomiting, emesis, neurokinin-1 receptor antagonists

  5. Benzoxazole derivatives suppress lipopolysaccharide-induced mast cell activation.

    Science.gov (United States)

    Cho, Kyung-Ah; Park, Minhwa; Kim, Yu-Hee; Choo, Hea-Young Park; Lee, Kyung Ho

    2018-05-01

    Mast cells are central regulators of allergic inflammation that function by releasing various proallergic inflammatory mediators, including histamine, eicosanoids and proinflammatory cytokines. Occasionally, bacterial infections may initiate or worsen allergic inflammation. A number of studies have indicated that activation of lipoxygenase in mast cells positive regulates allergic inflammatory responses by generating leukotrienes and proinflammatory cytokines. In the present study, the effects of benzoxazole derivatives on the lipopolysaccharide (LPS)‑induced expression of proinflammatory cytokines, production of histamine and surface expression of co‑stimulatory molecules on bone marrow-derived mast cells (BMMCs) were studied. The benzoxazole derivatives significantly reduced the expression of interleukin (IL)‑1β, IL‑6, IL‑13, tumor necrosis factor‑α, perilipin (PLIN) 2, and PLIN3 in BMMCs treated with LPS. Furthermore, histamine production was suppressed in BMMCs treated with LPS, or treated with phorbol-12-myristate-13-acetate/ionomycin. Benzoxazole derivatives marginally affected the surface expression of cluster of differentiation (CD)80 and CD86 on BMMCs in the presence of LPS, although LPS alone did not increase the expression of those proteins. Therefore, benzoxazole derivatives inhibited the secretion of proinflammatory cytokines in mast cells and may be potential candidate anti‑allergic agents to suppress mast cell activation.

  6. Evidence for a high and a low sensitivity receptor site for radiation-induced vomiting in the dog

    International Nuclear Information System (INIS)

    Harding, R.K.; Hugenholtz, H.; Kucharczyk, J.

    1987-01-01

    Ablation of the area postrema (AP) has been shown to prevent radiation-induced vomiting in the dog (induced by 6-8 By /sup 60/Co γ). In other species (cat, monkey) a higher dose of radiation is necessary to elicit emesis and visceral deafferentation has been more effective than AP ablation in preventing vomiting. The AP and the dorsal motor nucleus of the vagus (DMV), an important visceral afferent terminus, are anatomically adjacent structures in the medulla oblongata. Aggressive AP ablation could affect the DMV. The author's removed the AP in 6 dogs. Previous work showed this surgery prevented vomiting following exposure to 6-8 Gy. To prove the lesion did not invade the underlying DMV, the animals were given a hypertonic saline gavage, to elicit vomiting via visceral receptors. Animals were later submitted to 15-20 Gy. Those with proved visceral afferent connections vomited. They conclude that the AP is the most sensitive site for the stimulation of radiation-induced vomiting and that a less sensitive visceral site also exists. Differences in the relative sensitivities of these 2 systems may account for published species differences

  7. Induced Abortion

    Science.gov (United States)

    ... Education & Events Advocacy For Patients About ACOG Induced Abortion Home For Patients Search FAQs Induced Abortion Page ... Induced Abortion FAQ043, May 2015 PDF Format Induced Abortion Special Procedures What is an induced abortion? What ...

  8. Open-label observational study to assess the efficacy and safety of aprepitant for chemotherapy-induced nausea and vomiting prophylaxis in Indian patients receiving chemotherapy with highly emetogenic chemotherapy/moderately emetogenic chemotherapy regimens

    Directory of Open Access Journals (Sweden)

    Hingmire Sachin

    2015-01-01

    Full Text Available Context: Currently, there is limited data on the prevention of chemotherapy-induced nausea and vomiting (CINV in Indian population with aprepitant containing regimens. Aims: The aim was to assess the Efficacy and Safety of Aprepitant for the prevention of nausea and vomiting associated with highly emetogenic chemotherapy/moderately emetogenic chemotherapy (HEC/MEC regimens. Settings and Design: Investigator initiated, multicentric, open-label, prospective, noncomparative, observational trial. Subjects and Methods: Triple drug regimen with aprepitant, palonosetron, and dexamethasaone administration was assessed for the prevention of CINV during acute, delayed, and the overall phase (OP for HEC/MEC Regimens. The primary endpoint was complete response (CR; no emesis and no use of rescue medication and the key secondary endpoint was the complete control (CC; no emesis, no rescue medication and no more than mild nausea during the OP. Statistical Analysis Used: Perprotocol efficacy was analyzed for the first cycle with results represented in terms of CR/CC rates using descriptive statistics. Results: Seventy-five patients were included in the study with median age of 49.7 years and 89.7% being females. The CR rate (OP for patients administered HEC or MEC regimens during the first cycle were 92% and 90.9%, respectively. Similarly, the CC rates (OP were 75% and 90% for these regimens, respectively. 7 (9.2% patients reported adverse drug reactions that were mild and transient with no reports of any serious adverse events. Conclusions: Use of aprepitant containing regimen for patients receiving HEC/MEC regimen resulted in significantly high CR and CC response rates, which further consolidate its potential role to improve patient quality of life and compliance to disease management.

  9. Effects of Transdermal Tulobuterol in Pediatric Asthma Patients on Long-Term Leukotriene Receptor Antagonist Therapy: Results of a Randomized, Open-Label, Multicenter Clinical Trial in Japanese Children Aged 4–12 Years

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    Toshio Katsunuma

    2013-01-01

    Conclusions: These results suggest that short-term use of a transdermal β2 agonist is an effective therapy for pediatric asthma without inducing airway inflammation in children on long-term LTRA therapy.

  10. Ragweed-induced allergic rhinoconjunctivitis: current and emerging treatment options

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    Ihler F

    2015-02-01

    Full Text Available Friedrich Ihler, Martin CanisDepartment of Otorhinolaryngology, University Medical Center Göttingen, Göttingen, GermanyAbstract: Ragweed (Ambrosia spp. is an annually flowering plant whose pollen bears high allergenic potential. Ragweed-induced allergic rhinoconjunctivitis has long been seen as a major immunologic condition in Northern America with high exposure and sensitization rates in the general population. The invasive occurrence of ragweed (A. artemisiifolia poses an increasing challenge to public health in Europe and Asia as well. Possible explanations for its worldwide spread are climate change and urbanization, as well as pollen transport over long distances by globalized traffic and winds. Due to the increasing disease burden worldwide, and to the lack of a current and comprehensive overview, this study aims to review the current and emerging treatment options for ragweed-induced rhinoconjunctivitis. Sound clinical evidence is present for the symptomatic treatment of ragweed-induced allergic rhinoconjunctivitis with oral third-generation H1-antihistamines and leukotriene antagonists. The topical application of glucocorticoids has also been efficient in randomized controlled clinical trials. Combined approaches employing multiple agents are common. The mainstay of causal treatment to date, especially in Northern America, is subcutaneous immunotherapy with the focus on the major allergen, Amb a 1. Beyond this, growing evidence from several geographical regions documents the benefit of sublingual immunotherapy. Future treatment options promise more specific symptomatic treatment and fewer side effects during causal therapy. Novel antihistamines for symptomatic treatment are aimed at the histamine H3-receptor. New adjuvants with toll-like receptor 4 activity or the application of the monoclonal anti-immunoglobulin E antibody, omalizumab, are supposed to enhance conventional immunotherapy. An approach targeting toll-like receptor 9 by

  11. Exercise-Induced Wheezing among Japanese Pre-School Children and Pupils

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    Yoko Murakami

    2014-01-01

    Conclusions: EIW was not rare among current asthmatic children. An increased risk for EIW was in accordance with increasing severity of current asthma and this relation was mitigated with leukotriene receptor antagonist daily use among kindergartners.

  12. Review of mechanisms of deoxynivalenol-induced anorexia: The role of gut microbiota.

    Science.gov (United States)

    Peng, Zhao; Chen, Liangkai; Xiao, Jie; Zhou, Xiaoqi; Nüssler, Andreas K; Liu, Liegang; Liu, Jinping; Yang, Wei

    2017-09-01

    Deoxynivalenol (DON) is one of the most important mycotoxins in cereal-based foods or other food productions, produced by Fusarium species. Because of the high occurrence of DON in food combined with vast consumption of cereals and grain worldwide, the DON-contaminated food is a very harmful factor for human and animal health. DON has been reported to induce anorexia at lower or chronic doses in animal models. However, further researches for DON-induced anorexia are limited. Previous publications demonstrated a close link between Bacteroidetes and Firmicutes, two kinds of gut microbiota, with weight loss and the effect of low administration of DON on neurotransmitters in the frontal cortex, cerebellum, hypothalamus, hippocampus and pons/medulla. These data are similar to other studies, which show selective 5HT α receptor agonists apparently causing hyperphagia whereas 5HT 1β agonists appear to induce anorexia. Thus, the neurochemical effects of lower DON exposure can be as a result of peripheral toxicological events such as emesis, which overwhelmed its more subtle feed refusal activity. Besides, changes in the microbiota have an impact on stress-related behaviors like anxiety and depression, which can lead to weight loss through decreased feed intake. Gut dysbiosis is also associated with brain dysfunction and with behavioral changes. These conclusions illustrate as well a potential explanation for DON-induced anorexia.In this review, we summarize information about DON-induced anorexia from previous studies and provide our opinion for future investigations that could establish a link between gut microbiota, neurotransmitters, anorexia and weight loss under the DON exposure. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Reduced in vitro T-cell responses induced by glutaraldehyde-modified allergen extracts are caused mainly by retarded internalization of dendritic cells.

    Science.gov (United States)

    Heydenreich, Bärbel; Bellinghausen, Iris; Lorenz, Steffen; Henmar, Helene; Strand, Dennis; Würtzen, Peter A; Saloga, Joachim

    2012-06-01

    Although allergen-specific immunotherapy is a clinically effective therapy for IgE-mediated allergic diseases, the risk of IgE-mediated adverse effects still exists. For this reason, chemically modified allergoids have been introduced, which may destroy IgE-binding sites while T-cell activation should be retained. The aim of the study was to analyse the differences between intact allergens and differently modified/aggregated allergoids concerning their internalization as well as T-cell and basophil activation. For this purpose human monocyte-derived immature dendritic cells (DC) were incubated with Phleum pratense or Betula verrucosa pollen extract or with the corresponding allergoids, modified with formaldehyde or glutaraldehyde. After an additional maturation process, the antigen-loaded mature DC were co-cultured with autologous CD4(+) T cells. Allergenicity was tested by leukotriene release from basophils. In addition, the uptake of intact allergens and allergoids by immature DC was analysed. The proliferation of, as well as the interleukin-4 (IL-4), IL-10, IL-13 and interferon-γ production by, CD4(+) T cells which had been stimulated with glutaraldehyde allergoid-treated DC was reduced compared with CD4(+) T cells stimulated with intact allergen-treated or formaldehyde allergoid-treated DC. In line with this, glutaraldehyde-modified allergoids were more aggregated and were internalized more slowly. Furthermore, only the allergoids modified with glutaraldehyde induced a decreased leukotriene release by activated basophils. These findings suggest that IgE-reactive epitopes were destroyed more efficiently by modification with glutaraldehyde than with formaldehyde under the conditions chosen for these investigations. Glutaraldehyde-modified allergoids also displayed lower T-cell stimulatory capacity, which is mainly the result of greater modification/aggregation and diminished uptake by DC. © 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.

  14. Clinical roundtable monograph: New data in emerging treatment options for chemotherapy-induced nausea and vomiting.

    Science.gov (United States)

    Morrow, Gary R; Navari, Rudolph M; Rugo, Hope S

    2014-03-01

    Chemotherapy-induced nausea and vomiting (CINV) has long been one of the most troublesome adverse effects of chemotherapy, leading to significant detriments in quality of life and functioning, increased economic costs, and, in some cases, the discontinuation of effective cancer therapy. The past 2 decades have witnessed a dramatic increase in the number of effective antiemetic agents, with the introduction of the serotonin (5-hydroxytryptamine [5-HT₃]) receptor antagonists (ondansetron, granisetron, and palonosetron), the neurokinin-1 (NK₁) receptor antagonists (aprepitant and fosaprepitant), and the identification of other agents that have demonstrated efficacy against CINV, including corticosteroids. These agents often provide excellent control of emesis. Nausea, however, has proven more intractable, particularly in the days after administration of chemotherapy. Newer antiemetic agents under study may provide additional CINV control, particularly against delayed nausea. New agents undergoing review by the US Food and Drug Administration for the prevention of CINV include the novel NK₁ receptor antagonist rolapitant and a fixed-dose combination consisting of the novel NK₁ receptor antagonist netupitant and palonosetron (NEPA). Adherence to clinical practice guidelines has been shown to significantly improve CINV control. As antiemetic therapy continues to evolve, it will be important for clinicians to stay informed of new developments and changes in guidelines.

  15. Effects and Mechanisms of Transcutaneous Electroacupuncture on Chemotherapy-Induced Nausea and Vomiting

    Directory of Open Access Journals (Sweden)

    Xing Zhang

    2014-01-01

    Full Text Available Nausea and vomiting are one of the major complications of chemotherapy for cancers. The aim of this study is to investigate the emetic effects and mechanisms involving serotonin and dopamine of needleless transcutaneous electroacupuncture (TEA at Neiguan (PC6 and Jianshi (PC5 on chemotherapy-induced nausea and vomiting in patients with cancers. Seventy-two patients with chemotherapy were randomly divided into sham-TEA group (sham-TEA, n=34 and TEA group (n=38. TEA was performed at PC 6 and PC 5 (1 h, bid in combination with granisetron. Sham-TEA was delivered at nonacupoints using the same parameters. We found the following. (1 In the acute phase, the conventional antiemetic therapy using Ondansetron effectively reduced nausea and vomiting; the addition of TEA did not show any additive effects. In the delayed phase, however, TEA significantly increased the rate of complete control (P<0.01 and reduced the nausea score (P<0.05, compared with sham-TEA. (2 TEA significantly reduced serum levels of 5-HT and dopamine in comparison with sham-TEA. Those results demonstrate that needleless transcutaneous electroacupuncture at PC6 using a watch-size digital stimulator improves emesis and reduces nausea in the delayed phase of chemotherapy in patients with cancers. This antiemetic effect is possibly mediated via mechanisms involving serotonin and dopamine.

  16. Prophylaxis and management of antineoplastic drug induced nausea and vomiting in children with cancer

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    Sidharth Totadri

    2016-10-01

    Full Text Available Antineoplastic drug induced nausea and vomiting (AINV is a major adverse event which deeply impacts the quality of life of children with cancer. It additionally causes distress to parents and negatively impacts compliance to therapy. A robust AINV prophylaxis regimen is essential to achieve complete control; and prevent anticipatory, breakthrough and refractory AINV. With a wide array of available anti-emetics, standard guidelines for their use are crucial to ensure uniform and optimum prophylaxis. Chemotherapeutic agents are classified as having high, moderate, low or minimal emetic risk based on their potential to cause emesis in the absence of prophylaxis. Three drug regimen with aprepitant, ondansetron/granisetron and dexamethasone is recommended for protocols with high emetic risk. Although approved in children ≥12 years, there is mounting evidence for the use of aprepitant in younger children too. In protocols with moderate and low emetic risk, combination of ondansetron/granisetron and dexamethasone; and single agent ondansetron/granisetron are recommended, respectively. Metoclopramide is an alternative when steroids are contraindicated. Olanzapine and lorazepam are useful drugs for breakthrough AINV and anticipatory AINV. Knowledge of pediatric dosage, salient adverse events, drug interactions as well as cost of drugs is essential to prescribe anti-emetics accurately and safely in resource constrained settings. Non pharmacological interventions such as hypnosis, acupressure and psychological interventions can benefit a sub-group of patients without significant risk of adverse events.

  17. Carbamazepine for prevention of chemotherapy-induced nausea and vomiting: a pilot study

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    Thaiana Aragão Santana

    Full Text Available CONTEXT AND OBJECTIVE: Nausea and vomiting are major inconveniences for patients undergoing chemotherapy. Despite standard preventive treatment, chemotherapy-induced nausea and vomiting (CINV still occurs in approximately 50% of these patients. In an attempt to optimize this treatment, we evaluated the possible effects of carbamazepine for prevention of CINV.DESIGN AND LOCATION: Prospective nonrandomized open-label phase II study carried out at a Brazilian public oncology service. METHODS: Patients allocated for their first cycle of highly emetogenic chemotherapy were continuously recruited. In addition to standard antiemetic protocol that was made available, they received carbamazepine orally, with staggered doses, from the third day before until the fifth day after chemotherapy. Considering the sparseness of evidence about the efficacy of anticonvulsants for CINV prevention, we used Simon's two-stage design, in which 43 patients should be included unless overall complete prevention was not achieved in 9 out of the first 15 entries. The Functional Living Index-Emesis questionnaire was used to measure the impact on quality of life.RESULTS:None of the ten patients (0% presented overall complete prevention. In three cases, carbamazepine therapy was withdrawn because of somnolence and vomiting before chemotherapy. Seven were able to take the medication for the entire period and none were responsive, so the study was closed. There was no impact on the patients' quality of life.CONCLUSION: Carbamazepine was not effective for prevention of CINV and also had a deleterious side-effect profile in this population.

  18. Prevention of acute chemotherapy-induced nausea and vomiting: the role of palonosetron

    International Nuclear Information System (INIS)

    Bajetta, Emilio; Pusceddu, Sara; Guadalupi, Valentina; Ducceschi, Monika; Celio, Luigi

    2009-01-01

    Prevention of nausea and vomiting is the main goal of antiemetic treatment in cancer patients scheduled to receive chemotherapy. To prevent acute emesis, antiemetics should be administered just before chemotherapy and patients should be protected for up to 24 hours after chemotherapy initiation. The emetogenic potential of chemotherapeutic agents guides clinicians towards the most appropriate antiemetic prophylaxis. Current guidelines recommend the use of 5-HT 3 receptor antagonist (RA) either alone or in combination with dexamethasone and/or a neurokinin-1 RA both in the acute and delayed phases. The second-generation 5-HT 3 RA palonosetron exhibits a longer half-life and a higher binding affinity than older antagonists. Palonosetron has been approved by the FDA for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients scheduled to receive either moderately (MEC) or highly emetogenic chemotherapy (HEC) and for the prevention of delayed CINV in patients receiving MEC. The present review will discuss the role of palonosetron in the prevention of acute CINV

  19. Prevention of acute chemotherapy-induced nausea and vomiting: the role of palonosetron

    Directory of Open Access Journals (Sweden)

    Emilio Bajetta

    2009-08-01

    Full Text Available Emilio Bajetta, Sara Pusceddu, Valentina Guadalupi, Monika Ducceschi, Luigi CelioMedical Oncology Unit 2, Fondazione IRCCS “Istituto Nazionale dei Tumori”, Milan, ItalyAbstract: Prevention of nausea and vomiting is the main goal of antiemetic treatment in cancer patients scheduled to receive chemotherapy. To prevent acute emesis, antiemetics should be administered just before chemotherapy and patients should be protected for up to 24 hours after chemotherapy initiation. The emetogenic potential of chemotherapeutic agents guides clinicians towards the most appropriate antiemetic prophylaxis. Current guidelines recommend the use of 5-HT3 receptor antagonist (RA either alone or in combination with dexamethasone and/or a neurokinin-1 RA both in the acute and delayed phases. The second-generation 5-HT3RA palonosetron exhibits a longer half-life and a higher binding affinity than older antagonists. Palonosetron has been approved by the FDA for the prevention of chemotherapy-induced nausea and vomiting (CINV in patients scheduled to receive either moderately (MEC or highly emetogenic chemotherapy (HEC and for the prevention of delayed CINV in patients receiving MEC. The present review will discuss the role of palonosetron in the prevention of acute CINV.Keywords: antiemetics, chemotherapy, nausea, vomiting, serotonin-receptor antagonists, palonosetron

  20. Casopitant: a novel NK1-receptor antagonist in the prevention of chemotherapy-induced nausea and vomiting

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    Christina Ruhlmann

    2009-05-01

    Full Text Available Christina Ruhlmann, Jørn HerrstedtOdense University Hospital, Department of Oncology, Odense, DenmarkAbstract: Chemotherapy-induced nausea and vomiting (CINV are among the most feared and distressing symptoms experienced by patients with cancer. The knowledge of the pathogenesis and neuropharmacology of CINV has expanded enormously over the last decades, the most significant discoveries being the role of 5-hydroxytryptamine (5-HT3- and neurokinin (NK1 receptors in the emetic reflex arch. This has led to the development of two new classes of antiemetics acting as highly selective antagonists at one of these receptors. These drugs have had a huge impact in the protection from chemotherapy-induced vomiting, whereas the effect on nausea seems to be limited. The first NK1 receptor antagonist, aprepitant, became clinically available in 2003, and casopitant, the second in this class of antiemetics, has now completed phase III trials. This review delineates the properties and clinical use of casopitant in the prevention of CINV.Keywords: casopitant, GW679769, NK1 receptor antagonist, chemotherapy, emesis

  1. Therapeutic effects of arotinolol, a beta-adrenergic blocker, on tremor in MPTP-induced parkinsonian monkeys.

    Science.gov (United States)

    Kuno, S; Mizuta, E; Nishida, J; Takechi, M

    1992-10-01

    The effect of arotinolol, a peripherally acting beta-adrenergic-blocking agent, on postural or kinetic tremor was studied in monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Male cynomolgus monkeys (Macaca fascicularis) were treated with three injections of MPTP hydrochloride (0.3 mg/kg, i.v.) at an interval of 3-4 days, followed by several injections of the same dose every 7 days. Four monkeys with persistent parkinsonian symptoms manifested for greater than 1 year were used. The animals developed mild to moderate degrees of postural or kinetic tremor, and their motor activity was reduced. Arotinolol (20-30 mg/kg, s.c.) significantly suppressed postural tremor in a dose-dependent manner. Propranolol (20-30 mg/kg) was also effective in suppressing the tremor. However, the application of propranolol induced emesis, whereas arotinolol had no adverse effects. These results suggest that arotinolol is a useful adjunct to dopaminergic therapy for tremor in Parkinson's disease.

  2. Role of LTB4 in the pathogenesis of elastase-induced murine pulmonary emphysema

    Science.gov (United States)

    Paige, Mikell; Hanna, Halim; Kim, Su H.; Burdick, Marie D.; Strieter, Robert M.

    2010-01-01

    Exaggerated levels of the leukotriene B4 (LTB4) frequently coexist at sites of inflammation and tissue remodeling. Therefore, we hypothesize that the LTB4 pathway plays an important role in the pathogenesis of neutrophilic inflammation that contributes to pulmonary emphysema. In this study, significant levels of LTB4 were detected in human lung tissues with emphysema compared with lungs without emphysema (9,497 ± 2,839 vs. 4,142 ± 1,173 pg/ml, n = 9 vs. 10, P = 0.04). To further determine the biological role of LTB4 in the pathogenesis of emphysema, we compared the lungs of wild-type (WT) and LTA4 hydrolase−/− mice (LTB4 deficient, LTA4H−/−) exposed to intranasal elastase or vehicle control. We found that intranasal elastase induced accumulation of LTB4 in the lungs and caused progressively worsening emphysema between 14 and 28 days after elastase exposure in WT mice but not in LTA4H−/− mice. Premortem physiology documented increased lung compliance in elastase-exposed WT mice compared with elastase-exposed LTA4H−/− mice as measured by Flexivent (0.058 ± 0.005 vs. 0.041 ± 0.002 ml/cmH2O pressure). Postmortem morphometry documented increased total lung volume and alveolar sizes in elastase-exposed WT mice compared with elastase-exposed LTA4H−/− mice as measured by volume displacement and alveolar chord length assessment. Furthermore, elastase-exposed LTA4H−/− mice were found to have significantly delayed influx of the CD45highCD11bhighLy6Ghigh leukocytes compatible with neutrophils compared with elastase-exposed WT mice. Mechanistic insights to these phenotypes were provided by demonstrating protection from elastase-induced murine emphysema with neutrophil depletion in the elastase-exposed WT mice and by demonstrating time-dependent modulation of cysteinyl leukotriene biosynthesis in the elastase-exposed LTA4H−/− mice compared with elastase-exposed WT mice. Together, these findings demonstrated that LTB4 played an important role in

  3. Mediator profiles in tears during the conjunctival response induced by allergic reaction in the nasal mucosa.

    Science.gov (United States)

    Pelikan, Zdenek

    2013-01-01

    The allergic reaction occurring primarily in the nasal mucosa can induce a secondary conjunctival response of an immediate (SICR), late (SLCR), or delayed (SDYCR) type in some patients with allergic conjunctivitis (AC). To investigate the concentration changes of histamine, tryptase, eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), leukotrienes (LTB 4, LTC4, LTE4), myeloperoxidase (MPO), interferon-γ (IFN-γ), and interleukins (IL-2, IL-4, IL-5) in tears during the SICR, SLCR, and SDYCR. In 32 patients with AC, 11 SICR (ptears. The SICRs were associated with significant concentration changes in tears (ptears (ptears during the 32 PBS controls (p>0.1) or in the ten control patients (p>0.1). These results provide evidence for causal involvement of nasal allergy in some patients with AC, inducing secondary conjunctival response of immediate (SICR), late SLCR, or delayed SDYCR type, associated with different mediator, cytokine, and cellular profiles in the tears, suggesting involvement of different hypersensitivity mechanisms. These results also emphasize the diagnostic value of nasal allergen challenge combined with monitoring of the conjunctival response in some patients with AC.

  4. Ice massage on chemotherapy induced nausea and vomiting

    Directory of Open Access Journals (Sweden)

    Mehdi Sadeghi Shermeh

    2012-05-01

    Full Text Available Background and Aim: Nausea and vomiting are the most common side effects of chemotherapy. The aim of the current study was to assess the effect of ice massage applied to the pericardium 6 (P6 or Neigaun acupuncture point on nausea– vomiting due to chemotherapy in cancer patient. Materials and Methods: In a randomized clinical trial one- blind, 114 patients were randomly divided into three groups. Ice massage group were massaged gently on the skin around P6 point of the hand with ice cube into a wet gauze pad for 7 minutes twice a day with 12-hours interval for 24 hours by the patient. Placebo group were massaged with wooden cube and the control group received no interventions. Nausea and vomiting in three groups rated by Morrow Assessment of Nausea and Emesis (MANE Questionnaire in 4 periods of time in 24 hours was used for the assessment of nausea and vomiting. Results: There were significant decreases in the frequency of nausea (P<0.01 and vomiting (P<0.03 and a decrease in the intensity of nausea (P=0.63 and vomiting (P=0.34 in the case group. Frequency of nausea was significantly lower among placebo group than the control group (P<0.02. Conclusion: Ice massage on Neigaun point is effective on reducing the frequency of chemotherapy induced nausea and vomiting in cancer patients. Placebos, patient-practitioner relationship, suggestion, and the patient's view on nausea and vomiting and the role of interaction between the therapist and the patient is effective to some extent.

  5. Cannabinoid-Induced Hyperemesis: A Conundrum—From Clinical Recognition to Basic Science Mechanisms

    Directory of Open Access Journals (Sweden)

    Nissar A. Darmani

    2010-07-01

    Full Text Available Cannabinoids are used clinically on a subacute basis as prophylactic agonist antiemetics for the prevention of nausea and vomiting caused by chemotherapeutics. Cannabinoids prevent vomiting by inhibition of release of emetic neurotransmitters via stimulation of presynaptic cannabinoid CB1 receptors. Cannabis-induced hyperemesis is a recently recognized syndrome associated with chronic cannabis use. It is characterized by repeated cyclical vomiting and learned compulsive hot water bathing behavior. Although considered rare, recent international publications of numerous case reports suggest the contrary. The syndrome appears to be a paradox and the pathophysiological mechanism(s underlying the induced vomiting remains unknown. Although some traditional hypotheses have already been proposed, the present review critically explores the basic science of these explanations in the clinical setting and provides more current mechanisms for the induced hyperemesis. These encompass: (1 pharmacokinetic factors such as long half-life, chronic exposure, lipid solubility, individual variation in metabolism/excretion leading to accumulation of emetogenic cannabinoid metabolites, and/or cannabinoid withdrawal; and (2 pharmacodynamic factors including switching of the efficacy of Δ9-THC from partial agonist to antagonist, differential interaction of Δ9-THC with Gs and Gi signal transduction proteins, CB1 receptor desensitization or downregulation, alterations in tissue concentrations of endocannabinoid agonists/inverse agonists, Δ9-THC-induced mobilization of emetogenic metabolites of the arachidonic acid cascade, brainstem versus enteric actions of Δ9-THC, and/or hypothermic versus hyperthermic actions of Δ9-THC. In addition, human and animal findings suggest that chronic exposure to cannabis may not be a prerequisite for the induction of vomiting but is required for the intensity of emesis.

  6. Mechanisms of Radiation-Induced Conditioned Taste Aversion Learning

    Science.gov (United States)

    1986-01-01

    impairment of the synthesis of these cells, especially those in In addition to emesis. exposure to lower doses of ionizing bone marrow. However. since...pretreatment with fluoxetine in gustatory conditioning. 629-635. 1983. Pharmnat l Bioc/n-a 8,4,ui 17: 431-443. 1982. 100. Rabin. B. M. and J. S. Rabin

  7. Involvement of the Endocannabinoid System in the Development and Treatment of Breast Cancer

    Science.gov (United States)

    2013-02-01

    possesses antinociceptive actions in preclinical models of cancer pain (Guerrero et al. 2008) and can suppress radiation induced- emesis in the least...as, chemotherapy and radiation associated emesis in preclinical models. This could offer a third facet to WIN55,212-2’s mechanism of action, which... emesis in the least shrew. Eur J Pharmacol 563(1-3):187- 96. Guerrero AV, Quang P, Dekker N, Jordan RC, Schmidt BL. 2008. Peripheral cannabinoids

  8. Leukotriene D4 activates distinct G-proteins in intestinal epithelial cells to regulate stress fibre formation and to generate intracellular Ca2+ mobilisation and ERK1/2 activation

    International Nuclear Information System (INIS)

    Nielsen, Christian Kamp; Massoumi, Ramin; Sonnerlind, Maria; Sjoelander, Anita

    2005-01-01

    We have shown that the pro-inflammatory mediator LTD 4 , via its G-protein-coupled receptor CysLT 1 , signals through both pertussis-toxin-sensitive and -insensitive G-proteins to induce various cellular responses. To further characterise the initial step of the different signalling pathways emanating from the CysLT 1 receptor, we transfected intestinal epithelial cells, Int 407, with different mini vectors that each express a specific inhibitory peptide directed against a unique α subunit of a specific heterotrimeric G-protein. Our results revealed that LTD 4 -induced stress fibre formation is inhibited approximately 80% by a vector expressing an inhibitory peptide against the pertussis-toxin-insensitive Gα 12 -protein in intestinal epithelial Int 407 cells. Control experiments revealed that the LPA-induced stress fibre formation, mediated via the Gα 12 -protein in other cell types, was blocked by the same peptide in intestinal Int 407 cells. Furthermore, the CysLT 1 -receptor-mediated calcium signal and activation of the proliferative ERK1/2 kinase are blocked in cells transfected with a vector expressing an inhibitory peptide against the Gα i3 -protein, whereas in cells transfected with an empty ECFP-vector or vectors expressing inhibitory peptides against the Gα i1-2 -, Gα 12 -, Gα R -proteins these signals are not significantly affected. Consequently, the CysLT 1 receptor has the capacity to activate at least two distinctly different heterotrimeric G-proteins that transduce activation of unique downstream cellular events

  9. Anti-emetic principles of Inula linariaefolia flowers and Forsythia suspensa fruits.

    Science.gov (United States)

    Kinoshita, K; Kawai, T; Imaizumi, T; Akita, Y; Koyama, K; Takahashi, K

    1996-05-01

    The anti-emetic effects of 40 extracts made from 12 traditional Chinese herbal drugs were examined. Ten extracts inhibited emesis induced by copper sulfate pentahydrate; all were administered orally, and one extract inhibited emesis induced by apomorphine hydrochloride given to leopard and ranid frogs. Taraxasteryl palmitate and acetate, bigelovin and dihydrobigelovin were isolated from the CHCl(3) extract of Inula linariaefolia flowers, and identified as the active antiemetic agents when emesis was induced by copper sulfate. In addition, chlorogenic acid was isolated from the MeOH extract as an anti-emetic principle for the emesis induced by apomorphine hydrochloride. Rengyol, phillyrin and rutin were isolated from the MeOH extract of Forsythia suspensa fruits and identified as the inhibitors of emesis induced by copper sulfate pentahydrate. Copyright © 1996 Gustav Fischer Verlag · Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.

  10. CysLT1 receptor-induced human airway smooth muscle cells proliferation requires ROS generation, EGF receptor transactivation and ERK1/2 phosphorylation

    Directory of Open Access Journals (Sweden)

    Capra Valérie

    2006-03-01

    Full Text Available Abstract Background Cysteine-containing leukotrienes (cysteinyl-LTs are pivotal inflammatory mediators that play important roles in the pathophysiology of asthma, allergic rhinitis, and other inflammatory conditions. In particular, cysteinyl-LTs exert a variety of effects with relevance to the aetiology of asthma such as smooth muscle contraction, eosinophil recruitment, increased microvascular permeability, enhanced mucus secretion and decreased mucus transport and, finally, airway smooth muscle cells (ASMC proliferation. We used human ASMC (HASMC to identify the signal transduction pathway(s of the leukotriene D4 (LTD4-induced DNA synthesis. Methods Proliferation of primary HASMC was measured by [3H]thymidine incorporation. Phosphorylation of EGF receptor (EGF-R and ERK1/2 was assessed with a polyclonal anti-EGF-R or anti-phosphoERKl/2 monoclonal antibody. A Ras pull-down assay kit was used to evaluate Ras activation. The production of reactive oxygen species (ROS was estimated by measuring dichlorodihydrofluorescein (DCF oxidation. Results We demonstrate that in HASMC LTD4-stimulated thymidine incorporation and potentiation of EGF-induced mitogenic signaling mostly depends upon EGF-R transactivation through the stimulation of CysLT1-R. Accordingly, we found that LTD4 stimulation was able to trigger the increase of Ras-GTP and, in turn, to activate ERK1/2. We show here that EGF-R transactivation was sensitive to pertussis toxin (PTX and phosphoinositide 3-kinase (PI3K inhibitors and that it occurred independently from Src activity, despite the observation of a strong impairment of LTD4-induced DNA synthesis following Src inhibition. More interestingly, CysLT1-R stimulation increased the production of ROS and N-acetylcysteine (NAC abolished LTD4-induced EGF-R phosphorylation and thymidine incorporation. Conclusion Collectively, our data demonstrate that in HASMC LTD4 stimulation of a Gi/o coupled CysLT1-R triggers the transactivation of the EGF

  11. Effect of Ganoderma lucidum on pollen-induced biphasic nasal blockage in a guinea pig model of allergic rhinitis.

    Science.gov (United States)

    Mizutani, Nobuaki; Nabe, Takeshi; Shimazu, Masaji; Yoshino, Shin; Kohno, Shigekatsu

    2012-03-01

    Ganoderma lucidum (GL), an oriental medical mushroom, has been used in Asia for the prevention and treatment of a variety of diseases. However, the effect of GL on allergic rhinitis has not been well defined. The current study describes the inhibitory effect of GL on the biphasic nasal blockage and nasal hyperresponsiveness induced by repeated antigen challenge in a guinea pig model of allergic rhinitis. Intranasally sensitized guinea pigs were repeatedly challenged by inhalation of Japanese cedar pollen once every week. Ganoderma lucidum was orally administered once daily for 8 weeks from the time before the first challenge. The treatment with GL dose-dependently inhibited the early and late phase nasal blockage at the fifth to ninth antigen challenges. Furthermore, nasal hyperresponsiveness to intranasally applied leukotriene D₄ on 2 days after the eighth antigen challenge was also inhibited by the treatment with GL. However, Cry j 1-specific IgE antibody production was not affected by the treatment. In conclusion, we demonstrated that the pollen-induced biphasic nasal blockage and nasal hyperresponsiveness were suppressed by the daily treatment with GL in the guinea pig model of allergic rhinitis. These results suggest that GL may be a useful therapeutic drug for treating patients with allergic rhinitis. Copyright © 2011 John Wiley & Sons, Ltd.

  12. Effect of glucocorticosteroid treatment on ovalbumin-induced IgE-mediated immediate and late allergic response in guinea pig.

    Science.gov (United States)

    Andersson, P; Brange, C; von Kogerer, B; Sonmark, B; Stahre, G

    1988-01-01

    The effect of glucocorticosteroid (GCS) treatment on ovalbumine-induced IgE-mediated immediate and late allergic response was studied in sensitized guinea pigs. The results show that the GCS budesonide (BUD) inhibits the allergen-induced IgE-mediated immediate and late bronchial obstruction. The effect on the early reaction is correlated to the inhibition of leukotrienes and histamine release. The importance of mediator release inhibition for the antianaphylactic effect of GCS is discussed. In examining the effect on the late reaction, it was found that BUD had to be present during the early reaction but did not inhibit the early reaction. Furthermore, the effect on the late reaction was correlated to the inhibition of vascular leakage but not to the infiltration of inflammatory cells as examined in bronchoalveolar lavage. The results indicate that some triggering factors important for the development of the late reaction are released during the early reaction. Inhibition of the release of that factor or the activation of inflammatory cells by that factor might be the mechanism behind the antiinflammatory activities of GCS.

  13. 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.

    Science.gov (United States)

    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.

  14. 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

    Directory of Open Access Journals (Sweden)

    Helene Cawston

    2017-03-01

    Full Text Available 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

  15. Induced Seismicity

    Science.gov (United States)

    Keranen, Katie M.; Weingarten, Matthew

    2018-05-01

    The ability of fluid-generated subsurface stress changes to trigger earthquakes has long been recognized. However, the dramatic rise in the rate of human-induced earthquakes in the past decade has created abundant opportunities to study induced earthquakes and triggering processes. This review briefly summarizes early studies but focuses on results from induced earthquakes during the past 10 years related to fluid injection in petroleum fields. Study of these earthquakes has resulted in insights into physical processes and has identified knowledge gaps and future research directions. Induced earthquakes are challenging to identify using seismological methods, and faults and reefs strongly modulate spatial and temporal patterns of induced seismicity. However, the similarity of induced and natural seismicity provides an effective tool for studying earthquake processes. With continuing development of energy resources, increased interest in carbon sequestration, and construction of large dams, induced seismicity will continue to pose a hazard in coming years.

  16. A Review of NEPA, a Novel Fixed Antiemetic Combination with the Potential for Enhancing Guideline Adherence and Improving Control of Chemotherapy-Induced Nausea and Vomiting

    Directory of Open Access Journals (Sweden)

    Paul J. Hesketh

    2015-01-01

    Full Text Available Combination antiemetic regimens targeting multiple molecular pathways associated with emesis have become the standard of care for prevention of chemotherapy-induced nausea and vomiting (CINV related to highly and moderately emetogenic chemotherapies. Antiemetic consensus guidelines from several professional societies are widely available and updated regularly as new data emerges. Unfortunately, despite substantial research supporting the notion that guideline conformity improves CINV control, adherence to antiemetic guidelines is unsatisfactory. While studies are needed to identify specific barriers to guideline use and explore measures to enhance adherence, a novel approach has been taken to improve clinician adherence and patient compliance, with the development of a new combination antiemetic. NEPA is an oral fixed combination of a new highly selective NK1 receptor antagonist (RA, netupitant, and the pharmacologically and clinically distinct 5-HT3 RA, palonosetron. This convenient antiemetic combination offers guideline-consistent prophylaxis by targeting two critical pathways associated with CINV in a single oral dose administered only once per cycle. This paper will review and discuss the NEPA data in the context of how this first combination antiemetic may overcome some of the barriers interfering with adherence to antiemetic guidelines, enhance patient compliance, and offer a possible advance in the prevention of CINV for patients.

  17. Novel approach on the risk assessment of oxidized fats and oils for perspectives of food safety and quality. I. Oxidized fats and oils induces neurotoxicity relating pica behavior and hypoactivity.

    Science.gov (United States)

    Gotoh, N; Watanabe, H; Osato, R; Inagaki, K; Iwasawa, A; Wada, S

    2006-04-01

    Food poisoning caused by deteriorated fat and oil in instant noodles was first reported in Japan approximately 40 years ago. In these cases, many people developed neurotoxic symptoms such as emesis and discomfort. The degree of oxidation of the fat and oil in the instant noodles that induced food poisoning was at least 100 meq/kg in peroxide value (PV). No general toxicity studies with animals, however, have examined the toxicity of fat and oil oxidized to that extent. In this study, pica behavior, a behavior characterized by eating a nonfood material such as kaolin and that relates to the degree of discomfort in animals, and alterations of locomotor activity of rats eating deteriorated fat and oil were measured. The groups fed fat and oil with at least 138.5 meq/kg PV consumed significantly more kaolin compared to the control group. Furthermore, rats that ate deteriorated fat and oil with at least 107.2 meq/kg PV had significantly decreased locomotor activity compared to control rats. These phenomena suggest that oxidized fat and oil with at least 100 meq/kg PV induce neurotoxicity. The toxicity of oxidized fat and oil has only been addressed using general toxicity tests, but the present results reveal the importance of evaluating toxicity by using other measures.

  18. Management of chemotherapy-induced nausea and vomiting by risk profile: role of netupitant/palonosetron

    Directory of Open Access Journals (Sweden)

    Lorusso V

    2016-06-01

    Full Text Available Vito Lorusso National Cancer Research Centre, Istituto Tumori Giovanni Paolo II, Bari, Italy Abstract: As recommended by most recent antiemetic guidelines, the optimal prophylaxis of chemotherapy-induced nausea and vomiting (CINV requires the combination of 5-HT3 receptor antagonist (RA with an NK1-RA. Moreover, the major predictors of acute and delayed CINV include: young age, female sex, platinum- or anthracycline-based chemotherapy, nondrinker status, emesis in the earlier cycles of chemotherapy, and previous history of motion/morning sickness. Despite improved knowledge of the pathophysiology of CINV and advances in the availability of active antiemetics, an inconsistent compliance with their use has been reported, thereby resulting in suboptimal control of CINV in several cases. In this scenario, a new antiemetic drug is now available, which seems to be able to guarantee better prophylaxis of CINV and improvement of adherence to guidelines. In fact, netupitant/palonosetron (NEPA is a ready-to-use single oral capsule, combining an NK1-RA (netupitant and a 5-HT3-RA (palonosetron, which is to be taken 1 hour before the administration of chemotherapy, ensuring the coverage from CINV for 5 days. We reviewed the role of NEPA in patients at high risk of CINV receiving highly emetogenic chemotherapy. In these patients, NEPA plus dexamethasone, as compared to standard treatments, achieved superior efficacy in all primary and secondary end points during the acute, delayed, and overall phases, including nausea assessment. Moreover, these results were also achieved in female patients receiving anthracycline plus cyclophosphamide-based chemotherapy. NEPA represents a real step forward in the prophylaxis of CINV. Keywords: NEPA, netupitant, NK1, CINV, vomiting, risk factors

  19. Mechanisms of Broad-Spectrum Antiemetic Efficacy of Cannabinoids against Chemotherapy-Induced Acute and Delayed Vomiting

    Directory of Open Access Journals (Sweden)

    Nissar A. Darmani

    2010-09-01

    Full Text Available Chemotherapy-induced nausea and vomiting (CINV is a complex pathophysiological condition and consists of two phases. The conventional CINV neurotransmitter hypothesis suggests that the immediate phase is mainly due to release of serotonin (5-HT from the enterochromaffin cells in the gastrointestinal tract (GIT, while the delayed phase is a consequence of release of substance P (SP in the brainstem. However, more recent findings argue against this simplistic neurotransmitter and anatomical view of CINV. Revision of the hypothesis advocates a more complex, differential and overlapping involvement of several emetic neurotransmitters/modulators (e.g. dopamine, serotonin, substance P, prostaglandins and related arachidonic acid derived metabolites in both phases of emesis occurring concomitantly in the brainstem and in the GIT enteric nervous system (ENS [1]. No single antiemetic is currently available to completely prevent both phases of CINV. The standard antiemetic regimens include a 5-HT3 antagonist plus dexamethasone for the prevention of acute emetic phase, combined with an NK1 receptor antagonist (e.g. aprepitant for the delayed phase. Although NK1 antagonists behave in animals as broad-spectrum antiemetics against different emetogens including cisplatin-induced acute and delayed vomiting, by themselves they are not very effective against CINV in cancer patients. Cannabinoids such as D9-THC also behave as broad-spectrum antiemetics against diverse emetic stimuli as well as being effective against both phases of CINV in animals and patients. Potential side effects may limit the clinical utility of direct-acting cannabinoid agonists which could be avoided by the use of corresponding indirect-acting agonists. Cannabinoids (both phyto-derived and synthetic behave as agonist antiemetics via the activation of cannabinoid CB1 receptors in both the brainstem and the ENS emetic loci. An endocannabinoid antiemetic tone may exist since inverse CB1

  20. Effects of Acrolein on Leukotriene Biosynthesis in Human Neutrophils

    OpenAIRE

    Zemski Berry, Karin A.; Henson, Peter M.; Murphy, Robert C.

    2008-01-01

    Acrolein is a toxic, highly reactive α,β-unsaturated aldehyde that is present in high concentrations in cigarette smoke. In the current study, the effect of acrolein on eicosanoid synthesis in stimulated human neutrophils was examined. Eicosanoid synthesis in neutrophils was initiated by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF) and subsequent stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP) and 5-LO products in addition to small amounts of COX produc...

  1. Pharmacogenomics of inhaled corticosteroids and leukotriene modifiers : a systematic review

    NARCIS (Netherlands)

    Farzan, N.|info:eu-repo/dai/nl/412501929; Vijverberg, S.J.H.|info:eu-repo/dai/nl/325847460; Arets, H.G.M.; Raaijmakers, J.A.M.|info:eu-repo/dai/nl/072763299; van der Zee, A.H.|info:eu-repo/dai/nl/255164688

    BACKGROUND Pharmacogenetics studies of anti-inflammatory medication of asthma have expanded rapidly in recent decades, but the clinical value of their findings remains limited. OBJECTIVE To perform a systematic review of pharmacogenomics and pharmacogenetics of inhaled corticosteroids (ICS) and

  2. Chrysin protects against cisplatin-induced colon. toxicity via amelioration of oxidative stress and apoptosis: Probable role of p38MAPK and p53

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Rehan; Khan, Abdul Quaiyoom; Qamar, Wajhul; Lateef, Abdul; Tahir, Mir; Rehman, Muneeb U; Ali, Farrah; Sultana, Sarwat, E-mail: sarwat786@rediffmail.com

    2012-02-01

    Cisplatin, an antineoplastic drug, is widely used as a foremost therapy against numerous forms of cancer but it has pronounced adverse effects viz., nephrotoxicity, ototoxicity etc. CDDP-induced emesis and diarrhea are also marked toxicities that may be due to intestinal injury. Chrysin (5,7-dihydroxyflavone), a natural flavone commonly found in many plants possesses multiple biological activities, such as antioxidant, anti-inflammatory and anti-cancer effects. In the present study, we investigated the protective effect of chrysin against CDDP-induced colon toxicity. The plausible mechanism of CDDP-induced colon toxicity and damage includes oxidative stress, activation of p38MAPK and p53, and colonic epithelial cell apoptosis via upregulating the expression of Bak and cleaved caspase-3. Chrysin was administered to Wistar rats once daily for 14 consecutive days at the doses of 25 and 50 mg/kg body weight orally in corn oil. On day 14, a single intraperitoneal injection of cisplatin was given at the dose of 7.5 mg/kg body weight and animals were euthanized after 24 h of cisplatin injection. Chrysin ameliorated CDDP-induced lipid peroxidation, xanthine oxidase activity, glutathione depletion, decrease in antioxidant (catalase, glutathione reductase, glutathione peroxidase and glucose-6 phosphate dehydrogenase) and phase-II detoxifying (glutathione-S-transferase and quinone reductase) enzyme activities. Chrysin also attenuated goblet cell disintegration, expression of phospho-p38MAPK and p53, and apoptotic tissue damage which were induced by CDDP. Histological findings further supported the protective effects of chrysin against CDDP-induced colonic damage. The results of the present study suggest that the protective effect of chrysin against CDDP-induced colon toxicity was related with attenuation of oxidative stress, activation of p38MAPK and p53, and apoptotic tissue damage. Highlights: ► Cisplatin-induced colon toxicity is associated with oxidative stress and

  3. Chrysin protects against cisplatin-induced colon. toxicity via amelioration of oxidative stress and apoptosis: Probable role of p38MAPK and p53

    International Nuclear Information System (INIS)

    Khan, Rehan; Khan, Abdul Quaiyoom; Qamar, Wajhul; Lateef, Abdul; Tahir, Mir; Rehman, Muneeb U; Ali, Farrah; Sultana, Sarwat

    2012-01-01

    Cisplatin, an antineoplastic drug, is widely used as a foremost therapy against numerous forms of cancer but it has pronounced adverse effects viz., nephrotoxicity, ototoxicity etc. CDDP-induced emesis and diarrhea are also marked toxicities that may be due to intestinal injury. Chrysin (5,7-dihydroxyflavone), a natural flavone commonly found in many plants possesses multiple biological activities, such as antioxidant, anti-inflammatory and anti-cancer effects. In the present study, we investigated the protective effect of chrysin against CDDP-induced colon toxicity. The plausible mechanism of CDDP-induced colon toxicity and damage includes oxidative stress, activation of p38MAPK and p53, and colonic epithelial cell apoptosis via upregulating the expression of Bak and cleaved caspase-3. Chrysin was administered to Wistar rats once daily for 14 consecutive days at the doses of 25 and 50 mg/kg body weight orally in corn oil. On day 14, a single intraperitoneal injection of cisplatin was given at the dose of 7.5 mg/kg body weight and animals were euthanized after 24 h of cisplatin injection. Chrysin ameliorated CDDP-induced lipid peroxidation, xanthine oxidase activity, glutathione depletion, decrease in antioxidant (catalase, glutathione reductase, glutathione peroxidase and glucose-6 phosphate dehydrogenase) and phase-II detoxifying (glutathione-S-transferase and quinone reductase) enzyme activities. Chrysin also attenuated goblet cell disintegration, expression of phospho-p38MAPK and p53, and apoptotic tissue damage which were induced by CDDP. Histological findings further supported the protective effects of chrysin against CDDP-induced colonic damage. The results of the present study suggest that the protective effect of chrysin against CDDP-induced colon toxicity was related with attenuation of oxidative stress, activation of p38MAPK and p53, and apoptotic tissue damage. Highlights: ► Cisplatin-induced colon toxicity is associated with oxidative stress and

  4. Bloqueio do receptor de leucotrieno CysLT1 em pacientes com fenômeno de Raynaud: evidência capilaroscópica do papel do leucotrieno CysLT1 receptor inhibition in patients with Raynaud's phenomenon: capillaroscopic evidence of the role of leukotriene

    Directory of Open Access Journals (Sweden)

    Mario Newton Leitão de Azevedo

    2012-02-01

    Full Text Available OBJETIVO: Avaliar a ação do medicamento inibidor do receptor de leucotrieno CysLT1 (montelucaste nas alterações vasculares das mãos em pacientes com fenômeno de Raynaud. MÉTODOS: Foram selecionadas pacientes com fenômeno de Raynaud secundário à doença inflamatória do tecido conjuntivo, excluindo tabagismo, hipertensão arterial e diabetes mellitus. As pacientes mantiveram a medicação prévia e iniciaram o uso de montelucaste 10 mg/dia por 60 dias. Foi realizada capilaroscopia periungueal dos dedos das mãos antes do uso da medicação e após 30 e 60 dias. A análise estatística foi feita por meio de porcentagem, média, desvio-padrão e teste exato de Fisher, com intervalo de confiança de 95%. RESULTADOS: Foram estudadas cinco pacientes mulheres, brancas, com fenômeno de Raynaud secundário a doenças do tecido conjuntivo, das quais três apresentavam esclerodermia e duas apresentavam doença mista do tecido conjuntivo. A média de idade foi de 42,4 ± 12,4 anos, e a média de tempo de doença foi de 9,6 ± 4,8 anos. As pacientes estavam em uso de até 20 mg/dia de prednisona (pacientes com doença mista do tecido conjuntivo, nifedipina, pentoxifilina. As medicações foram mantidas. Após o uso de inibidor de receptor de leucotrieno por dois meses, o controle com capilaroscopia ungueal demonstrou diminuição do edema e da palidez e normalização do número, tamanho e distribuição dos capilares. CONCLUSÃO: O uso do montelucaste modificou as alterações capilares observadas na capilaroscopia periungueal de pacientes com fenômeno de RaynaudOBJECTIVE: To assess the effect of the leukotriene receptor inhibitor (montelukast on vascular alterations in fingers of patients with Raynaud's phenomenon. METHODS: Patients with Raynaud's phenomenon of the hands secondary to inflammatory connective tissue disease were selected, and those with the following characteristics were excluded: smokers, arterial hypertension, and diabetes

  5. Effects of drug treatment on inflammation and hyperreactivity of airways and on immune variables in cats with experimentally induced asthma.

    Science.gov (United States)

    Reinero, Carol R; Decile, Kendra C; Byerly, Jenni R; Berghaus, Roy D; Walby, William E; Berghaus, Londa J; Hyde, Dallas M; Schelegle, Edward S; Gershwin, Laurel J

    2005-07-01

    To compare the effects of an orally administered corticosteroid (prednisone), an inhaled corticosteroid (flunisolide), a leukotriene-receptor antagonist (zafirlukast), an antiserotonergic drug (cyproheptadine), and a control substance on the asthmatic phenotype in cats with experimentally induced asthma. 6 cats with asthma experimentally induced by the use of Bermuda grass allergen (BGA). A randomized, crossover design was used to assess changes in the percentage of eosinophils in bronchoalveolar lavage fluid (BALF); airway hyperresponsiveness; blood lymphocyte phenotype determined by use of flow cytometry; and serum and BALF content of BGA-specific IgE, IgG, and IgA determined by use of ELISAs. Mean +/- SE eosinophil percentages in BALF when cats were administered prednisone (5.0 +/- 2.3%) and flunisolide (2.5 +/- 1.7%) were significantly lower than for the control treatment (33.7 +/- 11.1%). We did not detect significant differences in airway hyperresponsiveness or lymphocyte surface markers among treatments. Content of BGA-specific IgE in serum was significantly lower when cats were treated with prednisone (25.5 +/- 5.4%), compared with values for the control treatment (63.6 +/- 12.9%); no other significant differences were observed in content of BGA-specific immunoglobulins among treatments. Orally administered and inhaled corticosteroids decreased eosinophilic inflammation in airways of cats with experimentally induced asthma. Only oral administration of prednisone decreased the content of BGA-specific IgE in serum; no other significant local or systemic immunologic effects were detected among treatments. Inhaled corticosteroids can be considered as an alternate method for decreasing airway inflammation in cats with asthma.

  6. Anti-Inflammatory benefits of antibiotic-induced neutrophil apoptosis: tulathromycin induces caspase-3-dependent neutrophil programmed cell death and inhibits NF-kappaB signaling and CXCL8 transcription.

    Science.gov (United States)

    Fischer, Carrie D; Beatty, Jennifer K; Zvaigzne, Cheryl G; Morck, Douglas W; Lucas, Merlyn J; Buret, A G

    2011-01-01

    Clearance of apoptotic neutrophils is a central feature of the resolution of inflammation. Findings indicate that immuno-modulation and induction of neutrophil apoptosis by macrolide antibiotics generate anti-inflammatory benefits via mechanisms that remain obscure. Tulathromycin (TUL), a new antimicrobial agent for bovine respiratory disease, offers superior clinical efficacy for reasons not fully understood. The aim of this study was to identify the immuno-modulating effects of tulathromycin and, in this process, to establish tulathromycin as a new model for characterizing the novel anti-inflammatory properties of antibiotics. Bronchoalveolar lavage specimens were collected from Holstein calves 3 and 24 h postinfection, challenged intratracheally with live Mannheimia haemolytica (2 × 10(7) CFU), and treated with vehicle or tulathromycin (2.5 mg/kg body weight). Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) staining and enzyme-linked immunosorbent assay (ELISA) revealed that tulathromycin treatment significantly increased leukocyte apoptosis and reduced levels of proinflammatory leukotriene B(4) in M. haemolytica-challenged calves. In vitro, tulathromycin concentration dependently induced apoptosis in freshly isolated bovine neutrophils from healthy steers in a capase-3-dependent manner but failed to induce apoptosis in bovine fibroblasts, epithelial cells, and endothelial cells, as well as freshly isolated bovine blood monocytes and monocyte-derived macrophages. The proapoptotic effects of TUL were also, in part, drug specific; equimolar concentrations of penicillin G, oxytetracycline, and ceftiofur failed to cause apoptosis in bovine neutrophils. In addition, tulathromycin significantly reduced levels of phosphorylated IκBα, nuclear translocation of NF-κB p65, and mRNA levels of proinflammatory interleukin-8 in lipopolysaccharide (LPS)-stimulated bovine neutrophils. The findings illustrate novel mechanisms through which

  7. Fasitibant chloride, a kinin B2 receptor antagonist, and dexamethasone interact to inhibit carrageenan-induced inflammatory arthritis in rats

    Science.gov (United States)

    Valenti, Claudio; Giuliani, Sandro; Cialdai, Cecilia; Tramontana, Manuela; Maggi, Carlo Alberto

    2012-01-01

    BACKGROUND AND PURPOSE Bradykinin, through the kinin B2 receptor, is involved in inflammatory processes related to arthropathies. B2 receptor antagonists inhibited carrageenan-induced arthritis in rats in synergy with anti-inflammatory steroids. The mechanism(s) underlying this drug interaction was investigated. EXPERIMENTAL APPROACH Drugs inhibiting inflammatory mediators released by carrageenan were injected, alone or in combination, into the knee joint of pentobarbital anaesthetized rats 30 min before intra-articular administration of carrageenan. Their effects on the carrageenan-induced inflammatory responses (joint pain, oedema and neutrophil recruitment) and release of inflammatory mediators (prostaglandins, IL-1β, IL-6 and the chemokine GRO/CINC-1), were assessed after 6 h. KEY RESULTS The combination of fasitibant chloride (MEN16132) and dexamethasone was more effective than each drug administered alone in inhibiting knee joint inflammation and release of inflammatory mediators. Fasitibant chloride, MK571, atenolol, des-Arg9-[Leu8]-bradykinin (B2 receptor, leukotriene, catecholamine and B1 receptor antagonists, respectively) and dexketoprofen (COX inhibitor), reduced joint pain and, except for the latter, also diminished joint oedema. A combination of drugs inhibiting joint pain (fasitibant chloride, des-Arg9-[Leu8]-bradykinin, dexketoprofen, MK571 and atenolol) and oedema (fasitibant chloride, des-Arg9-[Leu8]-bradykinin, MK571 and atenolol) abolished the respective inflammatory response, producing inhibition comparable with that achieved with the combination of fasitibant chloride and dexamethasone. MK571 alone was able to block neutrophil recruitment. CONCLUSIONS AND IMPLICATIONS Bradykinin-mediated inflammatory responses to intra-articular carrageenan were not controlled by steroids, which were not capable of preventing bradykinin effects either by direct activation of the B2 receptor, or through the indirect effects mediated by release of eicosanoids

  8. Effects of a self-management program on antiemetic-induced constipation during chemotherapy among breast cancer patients: a randomized controlled clinical trial.

    Science.gov (United States)

    Hanai, Akiko; Ishiguro, Hiroshi; Sozu, Takashi; Tsuda, Moe; Arai, Hidenori; Mitani, Akira; Tsuboyama, Tadao

    2016-01-01

    Research on patient-reported outcomes indicates that constipation is a common adverse effect of chemotherapy, and the use of 5-hydroxytryptamine (serotonin; 5HT3) receptor antagonists aggravates this condition. As cancer patients take multiple drugs as a part of their clinical management, a non-pharmacological self-management (SM) of constipation would be recommended. We aimed to evaluate the effectiveness of a SM program on antiemetic-induced constipation in cancer patients. Thirty patients with breast cancer, receiving 5HT3 receptor antagonists to prevent emesis during chemotherapy were randomly assigned to the intervention or control group. The SM program consisted of abdominal massage, abdominal muscle stretching, and education on proper defecation position. The intervention group started the program before the first chemotherapy cycle, whereas patients in the wait-list control group received the program on the day before their second chemotherapy cycle. The primary outcome was constipation severity, assessed by the constipation assessment scale (CAS, sum of eight components). The secondary outcome included each CAS component (0-2 points) and mood states. A self-reported assessment of satisfaction with the program was performed. The program produced a statistically and clinically significant alleviation of constipation severity (mean difference in CAS, -3.00; P = 0.02), decrease in the likelihood of a small volume of stool (P = 0.03), and decrease in depression and dejection (P = 0.02). With regards to program satisfaction, 43.6 and 26.4 % patients rated the program as excellent and good, respectively. Our SM program is effective for mitigating the symptoms of antiemetic-induced constipation during chemotherapy.

  9. Efficacy and safety of fosaprepitant for the prevention of nausea and emesis during 5 weeks of chemoradiotherapy for cervical cancer (the GAND-emesis study)

    DEFF Research Database (Denmark)

    Ruhlmann, Christina H; Christensen, Thomas Broe; Dohn, Line Hammer

    2016-01-01

    and dexamethasone in the prevention of nausea and vomiting during 5 weeks of fractionated radiotherapy and concomitant weekly cisplatin in patients with cervical cancer. METHODS: This investigator initiated, multinational, randomised, double-blind, placebo-controlled phase 3 trial, included women with cervical...... weeks of treatment. The modified intention-to-treat population (all patients who received study medication) was used for the statistical analyses. The study was registered with ClinicalTrials.gov, number NCT01074697. FINDINGS: Between June 15, 2010, and March 8, 2015, 246 patients from four countries...

  10. Granisetron in the treatment of radiotherapy-induced nausea and vomiting

    International Nuclear Information System (INIS)

    Hong, Seong Eon; Kang, Ji No

    1999-01-01

    Granisetron is a potent, the most selective 5-HT3 receptor antagonist and is reported to be effective in treatment of radiation-induced emesis. The antiemetic efficacy and safety of oral granisteron was evaluated in patients with receiving highly emetogenic treatment by conventional fractionated irradiation. Patients with various cancers who were being treated with irradiation were accrued into the present study. The intensity of nausea was evaluated on first 24 hours and on day-7 by patients according to the degree of interference with normal daily life as followings; a) none; b) present but no interference with normal daily life (mild); c) interference with normal daily life (moderate); and d) bedridden because of nausea (severe). Non or mild state was considered to indicate successful treatment. The efficacy of antiemetic treatment was graded as follows; a) complete response; no vomiting, no worse than mild nausea and receive no rescue antiementic therapy over the 24h period, b) major response; either one episode of vomiting or moderate/severe nausea or had received rescue medication over 24h period, or any combination of these, c) minor response; two to four episodes of vomiting over the 24h period, regardless of nausea and rescue medication, d) failure; more than four medication. The score of the most symptom m was recorded and the total score over 24 hours was summarized. The complete or major response was considered to indicate successful treatment. A total of 10 patients were enrolled into this study, and all were assessable for efficacy analysis. Total nausea control was achieved in 90% (9/10:none=60% plus mild=30%) of total patients after 7 days. The control of vomiting by granisteron was noted in seven patients (70%) of complete response and three (30%) of major response with a hundred-percent successful treatment over 7 days. The minor response or treatment failure were not observed. No significant adverse events or toxicities from granisetron were

  11. Granisetron in the treatment of radiotherapy-induced nausea and vomiting

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Seong Eon; Kang, Ji No [College of Medicine, Kyunghee Univ., Seoul (Korea, Republic of)

    1999-06-01

    Granisetron is a potent, the most selective 5-HT3 receptor antagonist and is reported to be effective in treatment of radiation-induced emesis. The antiemetic efficacy and safety of oral granisteron was evaluated in patients with receiving highly emetogenic treatment by conventional fractionated irradiation. Patients with various cancers who were being treated with irradiation were accrued into the present study. The intensity of nausea was evaluated on first 24 hours and on day-7 by patients according to the degree of interference with normal daily life as followings; a) none; b) present but no interference with normal daily life (mild); c) interference with normal daily life (moderate); and d) bedridden because of nausea (severe). Non or mild state was considered to indicate successful treatment. The efficacy of antiemetic treatment was graded as follows; a) complete response; no vomiting, no worse than mild nausea and receive no rescue antiementic therapy over the 24h period, b) major response; either one episode of vomiting or moderate/severe nausea or had received rescue medication over 24h period, or any combination of these, c) minor response; two to four episodes of vomiting over the 24h period, regardless of nausea and rescue medication, d) failure; more than four medication. The score of the most symptom m was recorded and the total score over 24 hours was summarized. The complete or major response was considered to indicate successful treatment. A total of 10 patients were enrolled into this study, and all were assessable for efficacy analysis. Total nausea control was achieved in 90% (9/10:none=60% plus mild=30%) of total patients after 7 days. The control of vomiting by granisteron was noted in seven patients (70%) of complete response and three (30%) of major response with a hundred-percent successful treatment over 7 days. The minor response or treatment failure were not observed. No significant adverse events or toxicities from granisetron were

  12. Inducing autophagy

    DEFF Research Database (Denmark)

    Harder, Lea M; Bunkenborg, Jakob; Andersen, Jens S.

    2014-01-01

    catabolism, which has recently been found to induce autophagy in an MTOR independent way and support cancer cell survival. In this study, quantitative phosphoproteomics was applied to investigate the initial signaling events linking ammonia to the induction of autophagy. The MTOR inhibitor rapamycin was used...... as a reference treatment to emphasize the differences between an MTOR-dependent and -independent autophagy-induction. By this means 5901 phosphosites were identified of which 626 were treatment-specific regulated and 175 were coregulated. Investigation of the ammonia-specific regulated sites supported that MTOR...

  13. Isoliquiritigenin induces growth inhibition and apoptosis through downregulating arachidonic acid metabolic network and the deactivation of PI3K/Akt in human breast cancer

    International Nuclear Information System (INIS)

    Li, Ying; Zhao, Haixia; Wang, Yuzhong; Zheng, Hao; Yu, Wei; Chai, Hongyan; Zhang, Jing; Falck, John R.; Guo, Austin M.; Yue, Jiang; Peng, Renxiu; Yang, Jing

    2013-01-01

    Arachidonic acid (AA)-derived eicosanoids and its downstream pathways have been demonstrated to play crucial roles in growth control of breast cancer. Here, we demonstrate that isoliquiritigenin, a flavonoid phytoestrogen from licorice, induces growth inhibition and apoptosis through downregulating multiple key enzymes in AA metabolic network and the deactivation of PI3K/Akt in human breast cancer. Isoliquiritigenin diminished cell viability, 5-bromo-2′-deoxyuridine (BrdU) incorporation, and clonogenic ability in both MCF-7 and MDA-MB-231cells, and induced apoptosis as evidenced by an analysis of cytoplasmic histone-associated DNA fragmentation, flow cytometry and hoechst staining. Furthermore, isoliquiritigenin inhibited mRNA expression of multiple forms of AA-metabolizing enzymes, including phospholipase A2 (PLA2), cyclooxygenases (COX)-2 and cytochrome P450 (CYP) 4A, and decreased secretion of their products, including prostaglandin E 2 (PGE 2 ) and 20-hydroxyeicosatetraenoic acid (20-HETE), without affecting COX-1, 5-lipoxygenase (5-LOX), 5-lipoxygenase activating protein (FLAP), and leukotriene B 4 (LTB 4 ). In addition, it downregulated the levels of phospho-PI3K, phospho-PDK (Ser 241 ), phospho-Akt (Thr 308 ), phospho-Bad (Ser 136 ), and Bcl-x L expression, thereby activating caspase cascades and eventually cleaving poly(ADP-ribose) polymerase (PARP). Conversely, the addition of exogenous eicosanoids, including PGE 2 , LTB 4 and a 20-HETE analog (WIT003), and caspase inhibitors, or overexpression of constitutively active Akt reversed isoliquiritigenin-induced apoptosis. Notably, isoliquiritigenin induced growth inhibition and apoptosis of MDA-MB-231 human breast cancer xenografts in nude mice, together with decreased intratumoral levels of eicosanoids and phospho-Akt (Thr 308 ). Collectively, these data suggest that isoliquiritigenin induces growth inhibition and apoptosis through downregulating AA metabolic network and the deactivation of PI3K/Akt in

  14. Effect of polyunsaturated fatty acids and their metabolites on bleomycin-induced cytotoxic action on human neuroblastoma cells in vitro.

    Directory of Open Access Journals (Sweden)

    Sailaja Polavarapu

    Full Text Available In the present study, we noted that bleomycin induced growth inhibitory action was augmented by all the polyunsaturated fatty acids (PUFAs tested on human neuroblastoma IMR-32 (0.5 × 10(4 cells/100 µl of IMR cells (EPA > DHA > ALA = GLA = AA > DGLA = LA: ∼ 60, 40, 30, 10-20% respectively at the maximum doses used. Of all the prostaglandins (PGE1, PGE2, PGF2α, and PGI2 and leukotrienes (LTD4 and LTE4 tested; PGE1, PGE2 and LTD4 inhibited the growth of IMR-32 cells to a significant degree at the highest doses used. Lipoxin A4 (LXA4, 19,20-dihydroxydocosapentaenoate (19, 20 DiHDPA and 10(S,17(S-dihydroxy-4Z,7Z,11E,13Z,15E,19Z-docosahexaenoic acid (protectin: 10(S,17(SDiHDoHE, metabolites of DHA, significantly inhibited the growth of IMR-32 cells. Pre-treatment with AA, GLA, DGLA and EPA and simultaneous treatment with all PUFAs used in the study augmented growth inhibitory action of bleomycin. Surprisingly, both indomethacin and nordihydroguaiaretic acid (NDGA at 60 and 20 µg/ml respectively enhanced the growth of IMR-32 cells even in the presence of bleomycin. AA enhanced oxidant stress in IMR-32 cells as evidenced by an increase in lipid peroxides, superoxide dismutase levels and glutathione peroxidase activity. These results suggest that PUFAs suppress growth of human neuroblastoma cells, augment growth inhibitory action of bleomycin by enhancing formation of lipid peroxides and altering the status of anti-oxidants and, in all probability, increase the formation of lipoxins, resolvins and protectins from their respective precursors that possess growth inhibitory actions.

  15. A randomized study of the efficacy and safety of transdermal granisetron in the control of nausea and vomiting induced by moderately emetogenic chemotherapy in Korean patients.

    Science.gov (United States)

    Kim, Jeong Eun; Hong, Yong Sang; Lee, Jae-Lyun; Kim, Kyu-Pyo; Park, Seong Joon; Sym, Sun Jin; Shin, Dong Bok; Lee, Jeeyun; Park, Young Suk; Ahn, Jin Seok; Kim, Tae Won

    2015-06-01

    The granisetron transdermal system (GTS) showed non-inferior efficacy to oral granisetron to control chemotherapy-induced nausea and vomiting (CINV) during multiday chemotherapy. We compared the efficacy and safety of GTS with that of intravenous and oral granisetron in Korean patients receiving moderately emetogenic chemotherapy (MEC). A total of 276 patients were randomized into GTS (n = 139, one patch on days 1-4) or control group (n = 137, intravenous on day 1 and oral on days 2-4). The primary endpoint was the percentage of patients achieving complete response (CR) from chemotherapy initiation until 24 h after the final administration. Out of 234 patients (112 in GTS and 122 in control group) included in the per protocol analysis, 97.9 % had gastrointestinal cancer and 76.9 % received 3-day chemotherapy. The GTS showed non-inferior efficacy achieving CR in 75.0 % of the patients; 74.6 % of the patients in the control group achieved CR (95 % confidence interval -10.73 to 11.55 %). The CR rate did not change after subgroup analyses by sex, age, and chemotherapy naivety and analysis per day and overall days of treatment. The GTS group showed sustained CR from day 1 to day 4. Patients' satisfaction, assessed using Functional Living Index-Emesis (FLI-E), showed no difference. Both treatments were well tolerated and safe. The GTS showed non-inferior efficacy to intravenous and oral granisetron. The safety, tolerability, and FLI-E scores of the GTS were comparable to those of control group. The GTS offers a convenient alternative option for relieving CINV in patients receiving MEC.

  16. A Randomized Controlled Pilot Study Comparing the Impact of Aprepitant and Fosaprepitant on Chemotherapy Induced Nausea and Vomiting in Patients Treated for Gynecologic Cancer.

    Science.gov (United States)

    Micha, John P; Rettenmaier, Mark A; Brown, John V; Mendivil, Alberto; Abaid, Lisa N; Lopez, Katrina L; Goldstein, Bram H

    2016-02-01

    The purpose of this pilot study was to compare the response rates and daily living activities of patients with newly diagnosed gynecologic cancer treated with fosaprepitant or aprepitant in the management of chemotherapy-induced nausea and vomiting. Eligible participants were randomized to either intravenous fosaprepitant (150 mg, day 1) or oral aprepitant (125 mg on day 1 and 80 mg on days 2-3) before undergoing weekly paclitaxel (80 mg/2)(2) and monthly carboplatin (AUC 6)-based chemotherapy. In addition, standard premedications (eg, ranitidine, dexamethasone, and diphenhydramine) were administered intravenously on day 1. Response evaluation and impact on daily life were measured throughout the acute phase (0-24 hours), delayed period (days 2-4), and overall phase (0-120 hours) of the patients' initial chemotherapy cycle via the Functional Living Index-Emesis. In the current investigation, 20 gynecologic cancer subjects were treated with either fosaprepitant (n = 10) or aprepitant (n = 10) before their first chemotherapy cycle. We observed 7 overall complete responses (70%, no emetic episodes or rescue medications) in the aprepitant group and 6 (60%) in the fosaprepitant cohort (P = 0.660). In addition, both treatment groups reported similarly, favorable rates of daily living activities throughout the acute (P = 0.626) and delayed (P = 0.648) phases of cycle 1 chemotherapy. The findings from the current analysis suggest that intravenous fosaprepitant and oral aprepitant confer beneficial antiemetic prevention. Moreover, the 2 medications theoretically afford a favorable impact on daily living, thereby potentially facilitating the completion of a patient's clinically prescribed chemotherapy regimen.

  17. Rikkunshito for Preventing Chemotherapy-Induced Nausea and Vomiting in Lung Cancer Patients: Results from 2 Prospective, Randomized Phase 2 Trials

    Directory of Open Access Journals (Sweden)

    Toshiyuki Harada

    2018-01-01

    Full Text Available The herbal medicine rikkunshito has the potential to improve chemotherapy-induced nausea and vomiting (CINV by stimulating ghrelin secretion. We aimed to evaluate the efficacy and safety of rikkunshito in preventing CINV for patients with lung cancer. Two separate prospective, randomized, phase II parallel design studies were conducted in patients with lung cancer. Fifty-eight and sixty-two patients scheduled to receive highly emetogenic chemotherapy (HEC and moderately emetogenic chemotherapy (MEC, respectively, were randomized 1:1 to receive either standard antiemetic therapy in accordance with international guidelines (S group or standard antiemetic therapy plus oral rikkunshito (R group. The primary endpoint was overall complete response (CR—that is, no emesis and rescue medication in the first 120 h post-chemotherapy. Secondary endpoints included CR in the acute (0–24 h and delayed (>24–120 h phases and safety. Fifty-seven patients (S group, 28; R group, 29 receiving HEC and sixty-two patients (S group, 30; R group, 32 receiving MEC with comparable characteristics were evaluated. The CR rates were similar across the S and R groups for the HEC study in the overall (67.9% vs. 62.1%, acute (96.4% vs. 89.6%, and delayed (67.9% vs. 62.1% phases, respectively, and for the MEC study in the overall (83.3% vs. 84.4%, acute (100% vs. 100%, and delayed (83.3% vs. 84.4% phases, respectively. No severe adverse events were observed. Although rikkunshito was well tolerated, it did not demonstrate an additional preventative effect against CINV in lung cancer patients receiving HEC or MEC.Clinical Trial Registry Information: This study is registered with the University Hospital Medical Information Network (UMIN Clinical Trial Registry1, identification numbers UMIN 000014239 and UMIN 000014240.

  18. Thalidomide for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy

    Directory of Open Access Journals (Sweden)

    Geng Song

    2017-03-01

    Full Text Available Background Antiemetic guidelines recommend co-administration of agents to maximize the prevention of chemotherapyinduced nausea and vomiting (CINV, however, the control of delayed CINV is still not satisfactory. The purpose of this study was to evaluate the effectiveness and safety of thalidomide in the prevention of CINV. Methods Of 89 patients enrolled, 83 chemotherapy-naïve patients receiving highly emetogenic chemotherapy (cisplatin 70mg/m2 were randomized into two groups: standard therapy group (ondansetron on day 1, metoclopramide and dexamethasone on days one to five and thalidomide group (in addition to standard emesis prevention, patients received oral 100mg thalidomide on days one to five. Patients recorded nausea and vomiting episodes in a diary. The primary end point was the efficacy of thalidomide in controlling vomiting and nausea on days one to five post cisplatin, and the secondary end point was the safety of the thalidomide. Results No significant differences of complete response rates (no emesis, no use of rescue therapy and no nausea were observed between the two groups, while the percentages of patients with complete response of delayed vomiting on day four and day five were higher in the thalidomide group, furthermore, the complete response rate of delayed nausea for thalidomide group and standard therapy group showed significant differences. Thalidomide group showed a similar safety profile as standard emesis prevention group. Conclusion Addition of thalidomide was generally well tolerated and improved prevention of CINV in patients receiving cisplatinbased chemotherapy to some degree, especially for delayed nausea.

  19. Macrophage migration inhibitory factor counter-regulates dexamethasone-induced annexin 1 expression and influences the release of eicosanoids in murine macrophages.

    Science.gov (United States)

    Sun, Yu; Wang, Yu; Li, Jia-Hui; Zhu, Shi-Hui; Tang, Hong-Tai; Xia, Zhao-Fan

    2013-10-01

    Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine and glucocorticoid (GC) counter-regulator, has emerged as an important modulator of inflammatory responses. However, the molecular mechanisms of MIF counter-regulation of GC still remain incomplete. In the present study, we investigated whether MIF mediated the counter-regulation of the anti-inflammatory effect of GC by affecting annexin 1 in RAW 264.7 macrophages. We found that stimulation of RAW 264.7 macrophages with lipopolysaccharide (LPS) resulted in down-regulation of annexin 1, while GC dexamethasone (Dex) or Dex plus LPS led to significant up-regulation of annexin 1 expression. RNA interference-mediated knockdown of intracellular MIF increased annexin 1 expression with or without incubation of Dex, whereas Dex-induced annexin 1 expression was counter-regulated by the exogenous application of recombinant MIF. Moreover, recombinant MIF counter-regulated, in a dose-dependent manner, inhibition of cytosolic phospholipase A2α (cPLA2α) activation and prostaglandin E2 (PGE2 ) and leukotriene B4 (LTB4 ) release by Dex in RAW 264.7 macrophages stimulated with LPS. Endogenous depletion of MIF enhanced the effects of Dex, reflected by further decease of cPLA2α expression and lower PGE2 and LTB4 release in RAW 264.7 macrophages. Based on these data, we suggest that MIF counter-regulates Dex-induced annexin 1 expression, further influencing the activation of cPLA2α and the release of eicosanoids. These findings will add new insights into the mechanisms of MIF counter-regulation of GC. © 2013 John Wiley & Sons Ltd.

  20. Zyflamend reduces LTB4 formation and prevents oral carcinogenesis in a 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced hamster cheek pouch model.

    Science.gov (United States)

    Yang, Peiying; Sun, Zheng; Chan, Diana; Cartwright, Carrie A; Vijjeswarapu, Mary; Ding, Jibin; Chen, Xiaoxin; Newman, Robert A

    2008-11-01

    Aberrant arachidonic acid metabolism, especially altered cyclooxygenase and 5-lipoxygenase (LOX) activities, has been associated with chronic inflammation as well as carcinogenesis in human oral cavity tissues. Here, we examined the effect of Zyflamend, a product containing 10 concentrated herbal extracts, on development of 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced inflammation and oral squamous cell carcinoma (SCC). A hamster cheek pouch model was used in which 0.5% DMBA was applied topically onto the left cheek pouch of male Syrian golden hamsters either three times per week for 3 weeks (short term) or 6 weeks (long term). Zyflamend was then applied topically at one of three different doses (25, 50 and 100 microl) onto the left cheek pouch three times for 1 week (short-term study) or chronically for 18 weeks. Zyflamend significantly reduced infiltration of inflammatory cells, incidence of hyperplasia and dysplastic lesions, bromodeoxyuridine-labeling index as well as number of SCC in a concentration-dependent manner. Application of Zyflamend (100 microl) reduced formation of leukotriene B(4) (LTB(4)) by 50% compared with DMBA-treated tissues. The reduction of LTB(4) was concentration dependent. The effect of Zyflamend on inhibition of LTB(4) formation was further confirmed with in vitro cell-based assay. Adding LTB(4) to RBL-1 cells, a rat leukemia cell line expressing high levels of 5-LOX and LTA(4) hydrolase, partially blocked antiproliferative effect of Zyflamend. This study demonstrates that Zyflamend inhibited LTB(4) formation and modulated adverse histopathological changes in the DMBA-induced hamster cheek pouch model. The study suggests that Zyflamend might prevent oral carcinogenesis at the post-initiation stage.

  1. Profile of netupitant/palonosetron (NEPA fixed dose combination and its potential in the treatment of chemotherapy-induced nausea and vomiting (CINV

    Directory of Open Access Journals (Sweden)

    Navari RM

    2014-12-01

    Full Text Available Rudolph M Navari Cancer Care Program, Eastern Europe, World Health Organization, Mishawaka, IN, USA; Indiana University School of Medicine, South Bend, IN, USA; South Bend Medical Services Corporation, IN, USA Abstract: Chemotherapy-induced nausea and vomiting (CINV is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a 5-hydroxytryptamine-3 (5-HT3 receptor antagonists, dexamethasone, and a neurokinin-1 (NK-1 receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. Palonosetron, a second generation 5-HT3 receptor antagonist with a different half-life, different binding capacity, and a different mechanism of action than the first generation 5-HT3 receptor antagonists, appears to be the most effective agent in its class. Netupitant, is a new NK-1 receptor antagonist with a high binding affinity, a long half-life of 90 hours, is metabolized by CYP3A4, and is an inhibitor of CYP3A4. NEPA is an oral fixed-dose combination of netupitant and palonosetron which has recently been employed in Phase II and Phase III clinical trials for the prevention of CINV in patients receiving moderately and highly emetogenic chemotherapy (MEC and HEC. The clinical trials demonstrated that NEPA (300 mg of netupitant plus 0.50 mg of palonosetron significantly improved the prevention of CINV compared to the use of palonosetron alone in patients receiving either HEC or MEC. The clinical efficacy was maintained over multiple cycles of chemotherapy. NEPA (Akynzeo® has recently been approved by the Food and Drug Administration (FDA to treat nausea and vomiting in patients undergoing cancer chemotherapy. Keywords: 5-HT3 receptor antagonists, NK-1 receptor antagonists, palonosetron, netupitant, chemotherapy-induced nausea and vomiting

  2. Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Comparative Study From Sudan

    Directory of Open Access Journals (Sweden)

    Alaa A.M. Osman

    2018-05-01

    Full Text Available Purpose: Chemotherapy-induced nausea and vomiting (CINV is a distressing adverse effect. Neurokinin-1 receptor antagonist (NK1RA–containing regimens are the standard regimens for CINV prophylaxis in patients with cancer receiving highly or moderately emetogenic chemotherapy (HEC or MEC. NK1RA agents are expensive and were not registered in Sudan. Recently, regimens containing olanzapine, the available and affordable medication in Sudan, were introduced as another option. This study aimed to compare the efficacy of an olanzapine-containing regimen with the antiemetic regimen that was currently used in our institute for CINV prophylaxis in HEC/MEC settings. Patients and Methods: The study prospectively compared an olanzapine-containing regimen (acute phase: olanzapine, ondansetron, dexamethasone; delayed phase: olanzapine, ondansetron with an ondansetron/dexamethasone regimen (acute phase: ondansetron, dexamethasone; delayed phase: ondansetron in adult patients with cancer receiving HEC or MEC. The study outcomes were complete response (CR; no emesis and no rescue medications and nausea control (no nausea, which were assessed in the acute (0 to 24 hours, delayed (24 to 120 hours, and overall (0 to 120 hours phases. Results: The study included 131 patients (olanzapine-containing: 50 patients; ondansetron/dexamethasone: 81 patients. CR and nausea control were higher in the olanzapine-containing than in the ondansetron/dexamethasone regimen (CR: acute phase, 86% v 71.6%; P = .086; delayed phase, 72% v 30.9%; P < .001; overall phase, 66% v 25.9%; P < .001; nausea control: acute phase, 86% v 74.1%; P = .127; delayed phase, 76% v 34.6%; P < .001; overall phase, 72% v 29.6%; P < .001. The major toxicity of olanzapine was grade 1 and 2 sedation or drowsiness (25 patients. Conclusion: An olanzapine-containing regimen has better efficacy for prevention of CINV in the HEC/MEC setting. Oncologists working in a limited-resource setting should be familiar

  3. Pathogenesis-based treatment of chemotherapy-induced nausea and vomiting--two new agents.

    Science.gov (United States)

    Navari, Rudolph M

    2003-01-01

    Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors (female gender, younger age, alcohol consumption, history of motion sickness) are the major risk factors for CINV. The use of 5-hydroxytryptamine3 (5-HT3) receptor antagonists plus dexamethasone has significantly improved the control of acute CINV, but delayed nausea and vomiting remains a significant clinical problem. Although the 5-HT3 receptor antagonists, dexamethasone, and metoclopramide have been used to prevent delayed CINV, only dexamethasone appears to have much efficacy with acceptable toxicity. Recent studies have introduced two new agents, palonosetron and aprepitant, for the prevention of both acute and delayed CINV. Palonosetron is a new 5-HT3 receptor antagonist with a longer half life and a higher binding affinity than older 5-HT3 receptor antagonists. It improves the complete response rate (no emesis, no need for rescue) of acute and delayed CINV in patients receiving moderately emetogenic chemotherapy compared to the older 5-HT3 receptor antagonists. The other agent, aprepitant, is the first agent available in the new drug class of neurokinin-1 receptor antagonists. When added to a standard regimen of a 5-HT3 receptor antagonist and dexamethasone in patients receiving highly emetogenic chemotherapy, it improves the complete response rate of acute CINV. Aprepitant also improves the complete response of delayed CINV when compared to placebo and when used in combination with dexamethasone compared to dexamethasone alone. Acute and delayed nausea may also be improved by aprepitant when used in combination with a 5-HT3 and dexamethasone prechemotherapy or with daily dosing for 3-5 days following chemotherapy. Based on these studies, new guidelines for the prevention of CINV are proposed. Future studies may consider the use of

  4. Olanzapine for chemotherapy-induced nausea and vomiting: systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Chelkeba L

    2017-03-01

    Full Text Available Background: Chemotherapy induced nausea and vomiting (CINV remains the most distressing event in patients receiving highly emetogenic chemotherapy (HEC or moderately emetogenic chemotherapy (MEC. Objective: Therefore, this meta-analysis was conducted to evaluate the efficacy of olanzapine containing regimen in preventing acute, delayed and overall phases of CINV. Methods: PubMed, EBSCO, and Cochrane central register of controlled trials electronic databases were searched to identify RCTs that compared the effects of olanzapine with non-olanzapine regimen in preventing CINV. Randomized clinical trials (RCTs that compared olanzapine containing regimen with non-olanzapine regimen were included. The primary outcomes were the percentage of patients achieving no vomiting or no nausea in acute, delayed and overall phases. Results: 13 RCTs that enrolled 1686 participants were included in this meta-analysis. 852 patients were assigned to olanzapine and 834 patients were assigned to non-olanzapine regimen (other standard antiemetic regimen. The percentages of no emesis achieved were 87.5%, 76.2%, 73.6% in olanzapine versus 76.7%, 61.8%, and 56.4% in non-olanzapine regimen in acute, delayed and overall phases, respectively. The percentages of no nausea were 82%, 64.3%, 61.6% in olanzapine group versus 71.3%, 41.8%, and 40.6% in non-olanzapine group in acute, delayed and overall phases, respectively. In general, olanzapine containing regimen achieved statistical superiority to non-olanzapine regimen in no vomiting endpoint in acute phase (OR 2.16; 95%CI 1.60 to 2.91, p<0.00001; I-square=5%; p=0.40, delayed phase (OR 2.28; 95%CI 1.1.46 to 3.54, p=0.0003; I-square=65%; p=0.001 and overall phase (OR 2.48; 95%CI 1.59 to 3.86, p<0.0001; I-square=69%; p< 0.0001. Conclusion: The current meta-analysis showed that olanzapine was statistically and clinically superior to non-olanzapine regimen in preventing CINV in most domains of the parameters.

  5. Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability

    International Nuclear Information System (INIS)

    Li, E.J.; Cook, J.A.; Spicer, K.M.; Wise, W.C.; Rokach, J.; Halushka, P.V.

    1990-01-01

    Resistance to endotoxin in essential fatty acid-deficient (EFAD) rats is associated with reduced synthesis of certain arachidonic acid metabolites. It was hypothesized that EFAD rats would manifest decreased vascular permeability changes during endotoxemia as a consequence of reduced arachidonic acid metabolism. To test this hypothesis, changes in hematocrit (HCT) and mesenteric localization rate of technetium-labeled human serum albumin (99mTc-HSA) and red blood cells (99mTc-RBC) were assessed in EFAD and normal rats using gamma-camera imaging. Thirty minutes after Salmonella enteritidis endotoxin, EFAD rats exhibited less hemoconcentration as determined by % HCT than normal rats. Endotoxin caused a less severe change in permeability index in the splanchnic region in EFAD rats than in normal rats (1.2 +/- 0.6 x 10(-3)min-1 vs. 4.9 +/- 1.7 x 10(-3)min-1 respectively, P less than 0.05). In contrast to 99mTc-HSA, mesenteric localization of 99mTc-RBC was not changed by endotoxin in control or EFAD rats. Supplementation with ethyl-arachidonic acid did not enhance susceptibility of EFAD rats to endotoxin-induced splanchnic permeability to 99mTc-HSA. Leukotrienes have been implicated as mediators of increased vascular permeability in endotoxin shock. Since LTC3 formation has been reported to be increased in EFA deficiency, we hypothesized that LTC3 may be less potent than LTC4. Thus the effect of LTC3 on mean arterial pressure and permeability was compared to LTC4 in normal rats. LTC3-induced increases in peak mean arterial pressure were less than LTC4 at 10 micrograms/kg (39 +/- 5 mm Hg vs. 58 +/- 4 mm Hg respectively, P less than 0.05) and at 20 micrograms/kg (56 +/- 4 mm Hg vs. 75 +/- 2 mm Hg respectively, P less than 0.05). LY171883 (30 mg/kg), an LTD4/E4 receptor antagonist, attenuated the pressor effect of LTC4, LTD4, and LTC3

  6. BLT1-mediated O-GlcNAcylation is required for NOX2-dependent migration, exocytotic degranulation and IL-8 release of human mast cell induced by Trichomonas vaginalis-secreted LTB4.

    Science.gov (United States)

    Min, Arim; Lee, Young Ah; Kim, Kyeong Ah; Shin, Myeong Heon

    2018-05-31

    Trichomonas vaginalis is a sexually-transmitted protozoan parasite that causes vaginitis and cervicitis. Although mast cell activation is important for provoking tissue inflammation during infection with parasites, information regarding the signaling mechanisms in mast cell activation and T. vaginalis infection is limited. O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). We investigated if O-GlcNAcylation was associated with mast cell activation induced by T. vaginalis-derived secretory products (TvSP). Modified TvSP collected from live trichomonads treated with the 5-lipooxygenase inhibitor AA861 inhibited migration of mast cells. This result suggested that mast cell migration was caused by stimulation of T. vaginalis-secreted leukotrienes. Using the BLT1 antagonist U75302 or BLT1 siRNA, we found that migration of mast cells was evoked via LTB 4 receptor (BLT1). Furthermore, TvSP induced protein O-GlcNAcylation and OGT expression in HMC-1 cells, which was prevented by transfection with BLT1 siRNA. TvSP-induced migration, ROS generation, CD63 expression and IL-8 release were significantly suppressed by pretreatmemnt with OGT inhibitor ST045849 or OGT siRNA. These results suggested that BLT1-mediated OGlcNAcylation was important for mast cell activation during trichomoniasis. Copyright © 2018. Published by Elsevier Masson SAS.

  7. Effect of accupancture on point Pe6 on emesis of first gestational trimester

    Directory of Open Access Journals (Sweden)

    Niroomanesh Sh

    1997-09-01

    Full Text Available Sixty pregnant women with the gestational age of 6-14 weeks who met the following criteria were selected: 1 Presence of nausea and vomiting. 2 Absence of other medical conditions that cause nausea and vomiting. 3 Negative history of medical treatment for at last three days prior to admission. 4 Negative for threatened abortion, molar and twin pregnancy. Cases were randomly divided into two groups. Mean age of the cases was 25.16 y (range: 16-37 y and not significantly different in the two groups. The two groups were also similar in gestational age, severity of nausea and vomiting, number of previous pregnancies and abortions, profession, working inside or outside the house, family income and education of patients and their spouses. In one group, Pe6 point of acupuncture was stimulated by TENS (once every 2 hours, 10 minutes each time, from the time of awakening. The other group received placebo. Both groups were hospitalized for 48 hours, and were evaluated for severity of nausea and vomiting, apetite, frequency of vomiting and VAS at their worst day, 24 hours prior to admission and 24 and 48 hours after admission. The two groups were similar in frequency of vomiting, VAS, appetite, and severity of nausea 24 hours prior to admission, and the worst degree of nausea and vomiting. However, a significant difference was observed in the severity of nausea and vomiting 24 and 48 hours after the adminission between TENS and placebo (P=0.000. In the group who received TENS, 24 cases (86.7% reported improvement (compared to 23.3% in the control group. Of all the cases, 81.6% had received prior medication, only 18.3% of the latter reported improvement with medication. Level of VAS in the groups with severe and mild to moderate nausea and vomiting was not significantly different in the first and second days of admission. Fifteen percent of the cases reported a transient cutaneous rash. Five cases were hospitalized more than once. Of the cases who reported improvement with TENS, 5% had improved after two stimulations, and 47% reported a relapse of symptoms in less than 24 hours after cessation of TENS. In one of the cases who were re-admitted, TENS did not result in alleviation of nausea and vomiting, and 56.6% of all the cases suggested to use TENS at home, 45% were attracted to TENS by commercial advertisements. Disscusion: Stimulation of Pe6 (Neiguan point alleviates the nausea and vomiting of pregnancy.

  8. A Phase II single-arm trial of palonosetron for the prevention of acute and delayed chemotherapy-induced nausea and vomiting in malignant glioma patients receiving multidose irinotecan in combination with bevacizumab

    Directory of Open Access Journals (Sweden)

    Affronti ML

    2016-12-01

    Full Text Available Mary Lou Affronti,1–3 Sarah Woodring,1,2 Katherine B Peters,1,4 James E Herndon II,5 Frances McSherry,5 Patrick N Healy,5 Annick Desjardins,1,4 James J Vredenburgh,6 Henry S Friedman1,2 1The Preston Robert Tisch Brain Tumor Center at Duke, South Hospital, Duke University Medical Center, 2Department of Neurosurgery, Duke University Health System, 3Duke University School of Nursing, 4Department of Neurology, 5Department of Biostatistics and Bioinformatics, Duke University Health System, Durham, NC, 6Saint Francis Cancer Center, Hartford, CT, USA Purpose: Given that the prognosis of recurrent malignant glioma (MG remains poor, improving quality of life (QoL through symptom management is important. Meta-analyses establishing antiemetic guidelines have demonstrated the superiority of palonosetron (PAL over older 5-hydroxytryptamine 3-receptor antagonists in chemotherapy-induced nausea and vomiting (CINV prevention, but excluded patients with gliomas. Irinotecan plus bevacizumab is a treatment frequently used in MG, but is associated with low (55% CINV complete response (CR; no emesis or use of rescue antiemetic with commonly prescribed ondansetron. A single-arm Phase II trial was conducted in MG patients to determine the efficacy of intravenous PAL (0.25 mg and dexamethasone (DEX; 10 mg received in conjunction with biweekly irinotecan–bevacizumab treatment. The primary end point was the proportion of subjects achieving acute CINV CR (no emesis or antiemetic ≤24 hours postchemotherapy. Secondary end points included delayed CINV CR (days 2–5, overall CINV CR (days 1–5, and QoL, fatigue, and toxicity.Materials and methods: A two-stage design of 160 patients was planned to differentiate between CINV CR of 55% and 65% after each dose of PAL–DEX. Validated surveys assessed fatigue and QoL.Results: A total of 63 patients were enrolled, after which enrollment was terminated due to slow accrual; 52 patients were evaluable for the primary outcome

  9. Exercise-Induced Asthma

    Science.gov (United States)

    ... Videos for Educators Search English Español Exercise-Induced Asthma KidsHealth / For Parents / Exercise-Induced Asthma What's in ... Exercise-Induced Asthma Print What Is Exercise-Induced Asthma? Most kids and teens with asthma have symptoms ...

  10. Randomized phase III trial of APF530 versus palonosetron in the prevention of chemotherapy-induced nausea and vomiting in a subset of patients with breast cancer receiving moderately or highly emetogenic chemotherapy

    International Nuclear Information System (INIS)

    Boccia, Ralph; O’Boyle, Erin; Cooper, William

    2016-01-01

    APF530 provides controlled, sustained-release granisetron for preventing acute (0–24 h) and delayed (24–120 h) chemotherapy-induced nausea and vomiting (CINV). In a phase III trial, APF530 was noninferior to palonosetron in preventing acute CINV following single-dose moderately (MEC) or highly emetogenic chemotherapy (HEC) and delayed CINV in MEC (MEC and HEC defined by Hesketh criteria). This exploratory subanalysis was conducted in the breast cancer subpopulation. Patients were randomized to subcutaneous APF530 250 or 500 mg (granisetron 5 or 10 mg) or intravenous palonosetron 0.25 mg during cycle 1. Palonosetron patients were randomized to APF530 for cycles 2 to 4. The primary efficacy end point was complete response (CR, no emesis or rescue medication) in cycle 1. Among breast cancer patients (n = 423 MEC, n = 185 HEC), > 70 % received anthracycline-containing regimens in each emetogenicity subgroup. There were no significant between-group differences in CRs in cycle 1 for acute (APF530 250 mg: MEC 71 %, HEC 77 %; 500 mg: MEC 73 %, HEC 73 %; palonosetron: MEC 68 %, HEC 66 %) and delayed (APF530 250 mg: MEC 46 %, HEC 58 %; 500 mg: MEC 48 %, HEC 63 %; palonosetron: MEC 52 %, HEC 52 %) CINV. There were no significant differences in within-cycle CRs between APF530 doses for acute and delayed CINV in MEC or HEC in cycles 2 to 4; CRs trended higher in later cycles, with no notable differences in adverse events between breast cancer and overall populations. APF530 effectively prevented acute and delayed CINV over 4 chemotherapy cycles in breast cancer patients receiving MEC or HEC. Clinicaltrials.gov identifier: NCT00343460 (June 22, 2006)

  11. Humoral and cellular responses to casein in patients with food protein-induced enterocolitis to cow's milk.

    Science.gov (United States)

    Caubet, Jean Christoph; Bencharitiwong, Ramon; Ross, Andrew; Sampson, Hugh A; Berin, M Cecilia; Nowak-Węgrzyn, Anna

    2017-02-01

    Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy manifesting within 1 to 4 hours of food ingestion with repetitive emesis and lethargy. We sought to characterize immune responses to casein in children with FPIES caused by cow's milk (CM). Total IgE and IgM, CM-specific IgG, and casein-specific IgE, IgG, IgG 4 , and IgM levels, as well as immunoglobulin free light chains, were measured in both patients with active and those with resolved CM-FPIES. Proliferating casein/T-effector cell counts were measured in children with CM-FPIES, children with IgE-mediated CM allergy, and those tolerating CM. Cytokine concentrations in the supernatants were quantified. Serum cytokine and tryptase levels were measured before and after a positive oral food challenge (OFC) result and compared with levels in those with a negative OFC result. We found low levels of CM and casein-specific IgG and casein-specific IgG 4 in patients with CM-FPIES versus those tolerating CM (P casein stimulation in children with CM-FPIES, results were similar to those in control subjects. Significantly lower secretion of IL-10 and higher secretion of IL-9 by casein-stimulated T cells were found in patients with CM-FPIES versus those with IgE-mediated CM allergy. Lower baseline serum levels of IL-10 and higher tryptase levels were found in active CM-FPIES versus resolved CM-FPIES. We found a significant increase in serum IL-10 and IL-8 levels after a positive OFC result. We confirm the paucity of humoral response in patients with CM-FPIES. IL-10 might play a key role in acquisition of tolerance in patients with CM-FPIES. Increased serum IL-8 levels in patients with active FPIES suggest neutrophil involvement. Elevated baseline serum tryptase levels in patients with active FPIES suggest low-grade intestinal mast cell activation or increased mast cell load. Copyright © 2016. Published by Elsevier Inc.

  12. Drug-induced thrombocytopenia

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Andersen, M; Hansen, P B

    1997-01-01

    induced by non-cytotoxic drugs is characterised by heterogeneous clinical picture and recovery is generally rapid. Although corticosteroids seem inefficient, we still recommend that severe symptomatic cases of drug-induced thrombocytopenia are treated as idiopathic thrombocytopenic purpura due...

  13. Leukotriene B4 catabolism: quantitation of leukotriene B4 and its omega-oxidation products by reversed-phase high-performance liquid chromatography.

    Science.gov (United States)

    Shak, S

    1987-01-01

    LTB4 and its omega-oxidation products may be rapidly, sensitively, and specifically quantitated by the methods of solid-phase extraction and reversed-phase high-performance liquid chromatography (HPLC), which are described in this chapter. Although other techniques, such as radioimmunoassay or gas chromatography-mass spectrometry, may be utilized for quantitative analysis of the lipoxygenase products of arachidonic acid, only the technique of reversed-phase HPLC can quantitate as many as 10 metabolites in a single analysis, without prior derivatization. In this chapter, we also reviewed the chromatographic theory which we utilized in order to optimize reversed-phase HPLC analysis of LTB4 and its omega-oxidation products. With this information and a gradient HPLC system, it is possible for any investigator to develop a powerful assay for the potent inflammatory mediator, LTB4, or for any other lipoxygenase product of arachidonic acid.

  14. Exercise-Induced Bronchoconstriction (EIB)

    Science.gov (United States)

    ... Conditions & Treatments ▸ Conditions Dictionary ▸ Exercise-Induced Bronchoconstriction Share | Exercise-Induced Bronchoconstriction (EIB) « Back to A to Z Listing Exercise-Induced Bronchoconstriction, (EIB), often known as exercise-induced ...

  15. Evidence for autocrine and paracrine regulation of allergen-induced mast cell mediator release in the guinea pig airways.

    Science.gov (United States)

    Yu, Li; Liu, Qi; Canning, Brendan J

    2018-03-05

    Mast cells play an essential role in immediate type hypersensitivity reactions and in chronic allergic diseases of the airways, including asthma. Mast cell mediator release can be modulated by locally released autacoids and circulating hormones, but surprisingly little is known about the autocrine effects of mediators released upon mast cell activation. We thus set out to characterize the autocrine and paracrine effects of mast cell mediators on mast cell activation in the guinea pig airways. By direct measures of histamine, cysteinyl-leukotriene and thromboxane release and with studies of allergen-evoked contractions of airway smooth muscle, we describe a complex interplay amongst these autacoids. Notably, we observed an autocrine effect of the cysteinyl-leukotrienes acting through cysLT 1 receptors on mast cell leukotriene release. We confirmed the results of previous studies demonstrating a marked enhancement of mast cell mediator release following cyclooxygenase inhibition, but we have extended these results by showing that COX-2 derived eicosanoids inhibit cysteinyl-leukotriene release and yet are without effect on histamine release. Given the prominent role of COX-1 inhibition in aspirin-sensitive asthma, these data implicate preformed mediators stored in granules as the initial drivers of these adverse reactions. Finally, we describe the paracrine signaling cascade leading to thromboxane synthesis in the guinea pig airways following allergen challenge, which occurs indirectly, secondary to cysLT 1 receptor activation on structural cells and/ or leukocytes within the airway wall, and a COX-2 dependent synthesis of the eicosanoid. The results highlight the importance of cell-cell and autocrine interactions in regulating allergic responses in the airways. Copyright © 2017. Published by Elsevier B.V.

  16. 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.

    Science.gov (United States)

    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.

  17. Relationship between traditional Chinese medicine constitutional types with chemotherapy-induced nausea and vomiting in patients with breast cancer: an observational study.

    Science.gov (United States)

    Liu, Yi; Pan, Ting; Zou, Wenjing; Sun, Ye; Cai, Yun; Wang, Rui; Han, Pingping; Zhang, Zhe; He, Qunying; Ye, Feng

    2016-11-09

    The theory of traditional Chinese medicine (TCM) constitution involves genetic characteristics, psychological factors, organ functions, and many other aspects. Studies have shown that TCM constitution is associated with HLA polymorphisms and has a genetic basis. A large number of Chinese studies have suggested that the clinical evolution of breast cancer may differ among patients with different TCM constitutions. In addition, patients with breast cancer and different TCM constitutions may have different degrees of myelosuppression after chemotherapy. Some studies have revealed that some constitutions may become predictive factors for death and morbidity of some diseases. The study was to investigate the risk factors among TCM constitutions for chemotherapy-induced nausea and vomiting (CINV) in patients with primary breast cancer undergoing chemotherapy. From September 2008 to January 2014, 612 patients who underwent surgery and chemotherapy for breast cancer in three hospitals in Xi'an, Shanxi province, underwent TCM constitution assessment using the Nine Basic Constitutions in Chinese Medicine Questionnaire before chemotherapy. CINV was monitored during treatments. Patients were asked to complete the Functional Living Index-Emesis (FLIE) questionnaire. The most severe CINV grade during chemotherapy was recorded according to the WHO standard. The relationships between TCM constitutions, CINV, and clinical and pathological characteristics of the cancers were assessed. There were no differences in the incidence of CINV among breast cancer patients receiving different chemotherapy regimens, and among patients with different TCM constitutions. The wetness-heat score was an independent risk factor for severe CINV (grade III-IV) (OR = 1.012, 95 % CI: 1.007-1.021, P < 0.001). In-depth analyses of the wetness-heat constitution showed that bitter taste/smelly mouth was an independent risk factor for severe CINV (OR = 1.209, 95 % CI: 1.035-1.412, P = 0

  18. Induced pluripotency with endogenous and inducible genes

    International Nuclear Information System (INIS)

    Duinsbergen, Dirk; Eriksson, Malin; Hoen, Peter A.C. 't; Frisen, Jonas; Mikkers, Harald

    2008-01-01

    The recent discovery that two partly overlapping sets of four genes induce nuclear reprogramming of mouse and even human cells has opened up new possibilities for cell replacement therapies. Although the combination of genes that induce pluripotency differs to some extent, Oct4 and Sox2 appear to be a prerequisite. The introduction of four genes, several of which been linked with cancer, using retroviral approaches is however unlikely to be suitable for future clinical applications. Towards developing a safer reprogramming protocol, we investigated whether cell types that express one of the most critical reprogramming genes endogenously are predisposed to reprogramming. We show here that three of the original four pluripotency transcription factors (Oct4, Klf4 and c-Myc or MYCER TAM ) induced reprogramming of mouse neural stem (NS) cells exploiting endogenous SoxB1 protein levels in these cells. The reprogrammed neural stem cells differentiated into cells of each germ layer in vitro and in vivo, and contributed to mouse development in vivo. Thus a combinatorial approach taking advantage of endogenously expressed genes and inducible transgenes may contribute to the development of improved reprogramming protocols

  19. Diet induced thermogenesis

    Directory of Open Access Journals (Sweden)

    Westerterp KR

    2004-08-01

    Full Text Available Objective Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. Methods Measuring conditions include nutritional status of the subject, physical activity and duration of the observation. Diet characteristics are energy content and macronutrient composition. Results Most studies measure diet-induced thermogenesis as the increase in energy expenditure above basal metabolic rate. Generally, the hierarchy in macronutrient oxidation in the postprandial state is reflected similarly in diet-induced thermogenesis, with the sequence alcohol, protein, carbohydrate, and fat. A mixed diet consumed at energy balance results in a diet induced energy expenditure of 5 to 15 % of daily energy expenditure. Values are higher at a relatively high protein and alcohol consumption and lower at a high fat consumption. Protein induced thermogenesis has an important effect on satiety. In conclusion, the main determinants of diet-induced thermogenesis are the energy content and the protein- and alcohol fraction of the diet. Protein plays a key role in body weight regulation through satiety related to diet-induced thermogenesis.

  20. Induced quantum conformal gravity

    International Nuclear Information System (INIS)

    Novozhilov, Y.V.; Vassilevich, D.V.

    1988-11-01

    Quantum gravity is considered as induced by matter degrees of freedom and related to the symmetry breakdown in the low energy region of a non-Abelian gauge theory of fundamental fields. An effective action for quantum conformal gravity is derived where both the gravitational constant and conformal kinetic term are positive. Relation with induced classical gravity is established. (author). 15 refs

  1. Induced radioactivity at CERN

    CERN Multimedia

    1970-01-01

    A description of some of the problems and some of the advantages associated with the phenomenon of induced radioactivity at accelerator centres such as CERN. The author has worked in this field for several years and has recently written a book 'Induced Radioactivity' published by North-Holland.

  2. Diet induced thermogenesis

    NARCIS (Netherlands)

    Westerterp, K.R.

    2004-01-01

    OBJECTIVE: Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. METHODS: Measuring

  3. Bleomycin-induced pneumonitis

    NARCIS (Netherlands)

    S. Sleijfer (Stefan)

    2001-01-01

    textabstractThe cytotoxic agent bleomycin is feared for its induction of sometimes fatal pulmonary toxicity, also known as bleomycin-induced pneumonitis (BIP). The central event in the development of BIP is endothelial damage of the lung vasculature due to bleomycin-induced

  4. Induced abortion in Taiwan.

    Science.gov (United States)

    Wang, P D; Lin, R S

    1995-04-01

    Induced abortion is widely practised in Taiwan; however, it had been illegal until 1985. It was of interest to investigate induced abortion practices in Taiwan after its legalization in 1985 in order to calculate the prevalence rate and ratio of induced abortion to live births and to pregnancies in Taiwan. A study using questionnaires through personal interviews was conducted on more than seventeen thousand women who attended a family planning service in Taipei metropolitan areas between 1991 and 1992. The reproductive history and sexual behaviour of the subjects were especially focused on during the interviews. Preliminary findings showed that 46% of the women had a history of having had an induced abortion. Among them, 54.8% had had one abortion, 29.7% had had two, and 15.5% had had three or more. The abortion ratio was 379 induced abortions per 1,000 live births and 255 per 1,000 pregnancies. The abortion ratio was highest for women younger than 20 years of age, for aboriginal women and for nulliparous women. When logistic regression was used to control for confounding variables, we found that the number of previous live births is the strongest predictor relating to women seeking induced abortion. In addition, a significant positive association exists between increasing number of induced abortions and cervical dysplasia.

  5. Contact Lens-Induced Discomfort and Inflammatory Mediator Changes in Tears.

    Science.gov (United States)

    Masoudi, Simin; Zhao, Zhenjun; Stapleton, Fiona; Willcox, Mark

    2017-01-01

    Studies indicate that contact lens (CL) discontinuation mostly occurs because of dryness and discomfort symptoms. This study aimed to investigate relationships between changes in the concentration of tear inflammatory mediators with subjective comfort ratings with CL wear and no contact lens wear between morning and evening. Forty-five subjects collected tears twice daily in the morning and in the evening with or without lenses. Comfort was rated subjectively on a scale from 1 to 100 (where 100 was extremely comfortable) just before each tear collection. Tear samples were assayed for complement components (C3 and C3a), leukotriene B4 (LTB4), secretory phospholipase A2 (sPLA2), secretory immunoglobulin A (sIgA), and bradykinin using commercially available immuno-based assay kits. Comfort ratings showed a statistically significant decline from morning to evening both with CL (89.0±10.1 AM vs. 76.7±15.2 PM; P0.05). Leukotriene B4 levels were slightly higher in CL (CL 43.4±12.6 pg/ml vs. No CL 39.4±13.4 pg/mL; P=0.034), whereas the concentration of LTB4, C3, C3a, and sIgA dropped by the end of the day in the presence or absence of lens wear (Ptear levels were not correlated with comfort ratings in any of the conditions. Leukotriene B4 had a higher concentration in the evening, and when measured as a ratio to sIgA, there was a trend for increased concentration of this mediator during CL wear. Although specific mediators showed changes from morning to evening with and without lens wear, most of these were not correlated with subjective comfort ratings in lens wear. The only mediator that showed an increase in concentration during the day and during lens wear was LTB4, and further studies on this mediator are warranted.

  6. Centrally located GLP-1 receptors modulate gastric slow waves and cardiovascular function in ferrets consistent with the induction of nausea.

    Science.gov (United States)

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

    2017-10-01

    Glucagon-like peptide-1 (GLP-1) receptor agonists are indicated for the treatment of Type 2 diabetes and obesity, but can cause nausea and emesis in some patients. GLP-1 receptors are distributed widely in the brain, where they contribute to mechanisms of emesis, reduced appetite and aversion, but it is not known if these centrally located receptors also contribute to a modulation of gastric slow wave activity, which is linked causally to nausea. Our aim was to investigate the potential of the GLP-1 receptor agonist, exendin-4, administered into the 3rd ventricle to modulate emesis, feeding and gastric slow wave activity. Thermoregulation and cardiovascular parameters were also monitored, as they are disturbed during nausea. Ferrets were used as common laboratory rodents do not have an emetic reflex. A guide cannula was implanted into the 3rd ventricle for delivering a previously established dose of exendin-4 (10nmol), which had been shown to induce emesis and behaviours indicative of 'nausea'. Radiotelemetry recorded gastric myoelectric activity (GMA; slow waves), blood pressure and heart rate variability (HRV), and core temperature; food intake and behaviour were also assessed. Exendin-4 (10nmol, i.c.v.) decreased the dominant frequency of GMA, with an associated increase in the percentage of bradygastric power (lasting ~4h). Food intake was inhibited in all animals, with 63% exhibiting emesis. Exendin-4 also increased blood pressure (lasting ~24h) and heart rate (lasting ~7h), decreased HRV (lasting ~24h), and caused transient hyperthermia. None of the above parameters were emesis-dependent. The present study shows for the first time that gastric slow waves may be modulated by GLP-1 receptors in the brain through mechanisms that appear independent from emesis. Taken together with a reduction in HRV, the findings are consistent with changes associated with the occurrence of nausea in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Dexametasona comparada à metoclopramida na profilaxia de vômitos pós-operatórios em crianças submetidas a procedimentos cirúrgicos ambulatoriais Dexametasona comparada a la metoclopramida en la prevención de vómitos pos-operatorios en niños sometidos a procedimientos quirúrgicos ambulatoriales Dexamethasone compared to metoclopramide in the prophylaxis of emesis in children undergoing ambulatory surgical procedures

    Directory of Open Access Journals (Sweden)

    Antonio Bedin

    2005-08-01

    medication to use for prophylaxis. This study aimed at verifying whether dexamethasone, as compared to metoclopramide, decreases the incidence of vomiting when intravenously administered to children anesthetized with sevoflurane for ambulatory pediatric surgeries. METHODS: Two hundred and thirty seven male children, aged 11 months to 12 years, physical status ASA I and II, undergoing hernia repair were included in this study. They were premedicated with oral midazolam. Anesthesia was induced and maintained with sevoflurane, nitrous oxide, and 1 µg.kg-1 fentanyl. Patients were divided in two groups: group D patients (n = 118 were given 150 µg.kg-1 dexamethasone at induction while group M (n = 119 received 150 µg.kg-1 metoclopramide at induction. The following parameters were evaluated: incidence of vomiting in the first 4 postoperative hours (PO, incidence of vomiting between 4 and 24 PO hours, NNT of both medications and RRR of dexamethasone as compared to metoclopramide. RESULTS: The incidence of vomiting was 9.32% for group D and 33.61% for group M during the first 4 PO hours, and 1.69% with dexamethasone and 3.36% with metoclopramide between 4 and 24 PO hours. RRR of dexamethasone related to metoclopramide in the first 4 hours was 72%. The number necessary to treat (NNT for dexamethasone was 3.25 and for metoclopramide it was 15.66. CONCLUSIONS: Dexamethasone is more effective than metoclopramide in decreasing the incidence of vomiting when used during anesthetic induction with sevoflurane associated to nitrous oxide and fentanyl.

  8. Photon induced reactions

    International Nuclear Information System (INIS)

    Mecking, B.A.

    1982-04-01

    Various aspects of medium energy nuclear reactions induced by real photons are reviewed. Special emphasis is put on high accuracy experiments that will become possible with the next generation of electron accelerators. (orig.)

  9. Induced Noise Control

    National Research Council Canada - National Science Library

    Maidanik, G

    2002-01-01

    The induced noise control parameter is defined in terms of the ratio of the stored energy in a master dynamic system, when it is coupled to an adjunct dynamic system, to that stored energy when the coupling is absent...

  10. Beam induced RF heating

    CERN Document Server

    Salvant, B; Arduini, G; Assmann, R; Baglin, V; Barnes, M J; Bartmann, W; Baudrenghien, P; Berrig, O; Bracco, C; Bravin, E; Bregliozzi, G; Bruce, R; Bertarelli, A; Carra, F; Cattenoz, G; Caspers, F; Claudet, S; Day, H; Garlasche, M; Gentini, L; Goddard, B; Grudiev, A; Henrist, B; Jones, R; Kononenko, O; Lanza, G; Lari, L; Mastoridis, T; Mertens, V; Métral, E; Mounet, N; Muller, J E; Nosych, A A; Nougaret, J L; Persichelli, S; Piguiet, A M; Redaelli, S; Roncarolo, F; Rumolo, G; Salvachua, B; Sapinski, M; Schmidt, R; Shaposhnikova, E; Tavian, L; Timmins, M; Uythoven, J; Vidal, A; Wenninger, J; Wollmann, D; Zerlauth, M

    2012-01-01

    After the 2011 run, actions were put in place during the 2011/2012 winter stop to limit beam induced radio frequency (RF) heating of LHC components. However, some components could not be changed during this short stop and continued to represent a limitation throughout 2012. In addition, the stored beam intensity increased in 2012 and the temperature of certain components became critical. In this contribution, the beam induced heating limitations for 2012 and the expected beam induced heating limitations for the restart after the Long Shutdown 1 (LS1) will be compiled. The expected consequences of running with 25 ns or 50 ns bunch spacing will be detailed, as well as the consequences of running with shorter bunch length. Finally, actions on hardware or beam parameters to monitor and mitigate the impact of beam induced heating to LHC operation after LS1 will be discussed.

  11. Vitiligo, drug induced (image)

    Science.gov (United States)

    ... this person's face have resulted from drug-induced vitiligo. Loss of melanin, the primary skin pigment, occasionally ... is the case with this individual. The typical vitiligo lesion is flat and depigmented, but maintains the ...

  12. Terahertz Induced Electromigration

    DEFF Research Database (Denmark)

    Strikwerda, Andrew; Zalkovskij, Maksim; Iwaszczuk, Krzysztof

    2014-01-01

    We report the first observation of THz-field-induced electromigration in subwavelength metallic gap structures after exposure to intense single-cycle, sub-picosecond electric field transients of amplitude up to 400 kV/cm.......We report the first observation of THz-field-induced electromigration in subwavelength metallic gap structures after exposure to intense single-cycle, sub-picosecond electric field transients of amplitude up to 400 kV/cm....

  13. Diet induced thermogenesis

    OpenAIRE

    Westerterp KR

    2004-01-01

    Objective Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. Methods Measuring conditions include nutritional status of the subject, physical activity and duration of the observation. Diet characteristics are energy content and macronutrient composition. Resu...

  14. Laser-induced interactions

    International Nuclear Information System (INIS)

    Green, W.R.

    1979-01-01

    This dissertation discusses some of the new ways that lasers can be used to control the energy flow in a medium. Experimental and theoretical considerations of the laser-induced collision are discussed. The laser-induced collision is a process in which a laser is used to selectively transfer energy from a state in one atomic or molecular species to another state in a different species. The first experimental demonstration of this process is described, along with later experiments in which lasers were used to create collisional cross sections as large as 10 - 13 cm 2 . Laser-induced collisions utilizing both a dipole-dipole interaction and dipole-quadrupole interaction have been experimentally demonstrated. The theoretical aspects of other related processes such as laser-induced spin-exchange, collision induced Raman emission, and laser-induced charge transfer are discussed. Experimental systems that could be used to demonstrate these various processes are presented. An experiment which produced an inversion of the resonance line of an ion by optical pumping of the neutral atom is described. This type of scheme has been proposed as a possible method for constructing VUV and x-ray lasers

  15. Radiation-induced apoptosis

    International Nuclear Information System (INIS)

    Ohyama, Harumi

    1995-01-01

    Apoptosis is an active process of gene-directed cellular self-destruction that can be induced in many cell types via numerous physiological and pathological stimuli. We found that interphasedeath of thymocytes is a typical apoptosis showing the characteristic features of apoptosis including cell shrinkage, chromatin condensation and DNA degradation. Moderate dose of radiation induces extensive apoptosis in rapidly proliferating cell population such as the epithelium of intestinal crypt. Recent reports indicate that the ultimate form of radiation-induced mitotic death in several cells is also apoptosis. One of the hallmarks of apoptosis is the enzymatic internucleosomal degradation of chromatin DNA. We identified an endonuclease responsible for the radiation-induced DNA degradation in rat thymocytes. The death-sparing effects of interrupting RNA and protein synthesis suggested a cell genetic program for apoptosis. Apoptosis of thymocytes initiated by DNA damage, such as radiation and radio mimetic substance, absolutely requires the protein of p53 cancer suppresser gene. The cell death induced by glucocorticoid, or aging, has no such requirement. Expression of oncogene bcl-2 rescues cells from the apoptosis. Massive apoptosis in radiosensitive cells induced by higher dose radiation may be fatal. It is suggested that selective apoptotic elimination of cells would play an important role for protection against carcinogenesis and malformation through removal of cells with unrepaired radiation-induced DNA damages. Data to evaluate the significance of apoptosis in the radiation risk are still poor. Further research should be done in order to clarify the roles of the cell death on the acute and late effects of irradiation. (author)

  16. Development of 125I-leukotriene B4 radio-immunoassay and its clinical applications

    International Nuclear Information System (INIS)

    Wang Zhaoyue; He Yang; Chen Dechun; Ruan Changgeng

    1992-11-01

    LTB 4 was extracted from porcine blood with the help of HPLC. The antiserum was raised by immunizing rabbits with LTB 4 which has been conjugated with bovine serum albumin by mixed anhydride method method. The titer of the anti-body was 1:7000 and the affinity coefficient was 2.1 x 10 9 L/M. Its cross reactions with LTA 4 , LTC 4 , LTD 4 and other arachidonic acid metabolites were 0.4 ∼ 6.4%.The 125 I-histamine-LTB 4 was prepared by using chloramine T procedure. The minimum detectable limit was 25 pg/tube. The recovery rate was 84.2 ∼ 113%. The intra- and inter-assay coefficient of variation were 5.2% and 9.7% respectively. The amount of LTB 4 produced by normal human PMNL which were stimulated by ionophore A23187 and arachidonic acid was 695.5 ± 329.7 pg/10 6 cells. PMNL of patients with various acute leukemias and CML generated an increased quantities of LTB 4 , TXB 2 and 6-keto-PGF 1α . LTB 4 produced by PMNL also showed an increasing tendency in both cerebral thrombosis and acute myocardial infarction, but was not altered in cerebral hemorrhage of non-infarction coronary disease

  17. Bronchial effects of leukotriene D4 inhalation in normal human lung

    DEFF Research Database (Denmark)

    Bisgaard, H; Groth, S

    1987-01-01

    obstruction had decreased by 50% of the maximum effect, and no delayed reaction was observed within 10 h. The reactivity of the airways did not change during 10 h after inhalation of LTD4 as tested by repeated exercise challenges. Pretreatment with ipratropium bromide prevented the effect of LTD4 on FEV1, yet...

  18. A short synthesis and its application to the preparation of radio labelled leukotriene inhibitor Sch 37224

    International Nuclear Information System (INIS)

    Duelfer, T.; Gala, D.

    1991-01-01

    A new, short synthesis of 1-(1,2-dihydro-4-hydroxyl-1-phenyl-2-oxo-1,8-naphthyridin-3-yl)-pyrrolidinium hydroxide, inner salt, 1, was achieved by condensing methyl 2-phenylamino-3-pyridine carboxylate 2 with ethyl 1-pyrrolidine acetate 4. This gave highly pure product in 60% yield. This synthesis was applied to the preparation of 14 C labelled 1. Radiolabelled 1 was synthesized from u-[ 14 C]-aniline in three steps at 97% radiochemical purity and 27.3% radiochemical yield. (author)

  19. A specific assay for leukotriene B4 in human whole blood

    DEFF Research Database (Denmark)

    Fogh, J; Poulsen, L K; Bisgaard, H

    1992-01-01

    between standard and sample dilution curves. Purification was, therefore, extended by combinations of the following steps: 1) protein precipitation, 2) lipid extractions, and 3) high-performance liquid chromatography (HPLC). One of two commercially available LTB4 standards was found to contain multiple...... components, several of which were immunoreactive in RIA. Even for the standard containing pure LTB4, interference was demonstrated by lack of parallelism between sample and standard dilution curves. Testing eight combinations of varying purification steps, we found that only a three-step purification...

  20. Study of urinary leukotriene E4 in atopic dermatitis: relation to ...

    African Journals Online (AJOL)

    Ehab

    I-Complete blood count using Coulter cell counter. T660 (Coulter corporation, Florida, USA) with examination ... The results displayed are corrected values. IV- Quantitative determination of serum IgE concentrations: 2 ml of venous blood were collected in a tube, left to clot and centrifuged at. 1500 rpm to separate the serum.

  1. Chemical-induced Vitiligo

    Science.gov (United States)

    Harris, John E.

    2016-01-01

    Synopsis Chemical-induced depigmentation of the skin has been recognized for over 75 years, first as an occupational hazard but then extending to those using household commercial products as common as hair dyes. Since their discovery, these chemicals have been used therapeutically in patients with severe vitiligo to depigment their remaining skin and improve their appearance. The importance of recognizing this phenomenon was highlighted during an outbreak of vitiligo in Japan during the summer of 2013, when over 16,000 users of a new skin lightening cosmetic cream developed skin depigmentation at the site of contact with the cream and many in remote areas as well. Depigmenting chemicals appear to be analogs of the amino acid tyrosine that disrupt melanogenesis and result in autoimmunity and melanocyte destruction. Because chemical-induced depigmentation is clinically and histologically indistinguishable from non-chemically induced vitiligo, and because these chemicals appear to induce melanocyte autoimmunity, this phenomenon should be known as “chemical-induced vitiligo”, rather than less accurate terms that have been previously used. PMID:28317525

  2. [Drug induced diarrhea].

    Science.gov (United States)

    Morard, Isabelle; Hadengue, Antoine

    2008-09-03

    Diarrhea is a frequent adverse event involving the most frequently antibiotics, laxatives and NSAI. Drug induced diarrhea may be acute or chronic. It may be due to expected, dose dependant properties of the drug, to immuno-allergic or bio-genomic mechanisms. Several pathophysiological mechanisms have been described resulting in osmotic, secretory or inflammatory diarrhea, shortened transit time, or malabsorption. Histopathological lesions sometimes associated with drug induced diarrhea are usually non specific and include ulcerations, inflammatory or ischemic lesions, fibrous diaphragms, microscopic colitis and apoptosis. The diagnosis of drug induced diarrhea, sometimes difficult to assess, relies on the absence of other obvious causes and on the rapid disappearance of the symptoms after withdrawal of the suspected drug.

  3. Rosuvastatin-induced pemphigoid.

    LENUS (Irish Health Repository)

    Murad, Aizuri A

    2012-01-01

    Statins are widely prescribed medications and very well tolerated. Rosuvastatin is another member of this drug used to treat dyslipidaemia. It is a competitive inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase. Immunobullous disease is usually idiopathic but can be drug-induced. Both idiopathic and iatrogenic forms share common clinical and immunohistological features. The authors report a case of pemphigoid induced by rosuvastatin, a commonly prescribed medication. To our knowledge, there is limited report on rosuvastatin associated with pemphigoid in the literature.

  4. Cervical osteophyte induced dysphagia

    International Nuclear Information System (INIS)

    Davies, R.P.; Sage, M.R.; Brophy, B.P.

    1989-01-01

    Although cervical spondylosis is a common disorder, dysphagia induced by osteophyte formation is uncommon. Fewer than one hundred cases of cervical osteophyte induced dysphagia have been reported, with little attention to the diagnosis by barium swallow. The radiological features of two cases treated surgically with good results are described. Both cases complained of dysphagia while one had associated respiratory obstruction on forward flexion of his neck. The features on barium study of cervical osteophytes causing dysphagia include deformity at the level of osteophyte formation, in both AP and lateral projections. Tracheal aspirations due to deformity at the laryngeal inlet and interference with epiglottic retroversion may be present. 8 refs., 3 figs

  5. Exercise-induced rhabdomyolysis.

    Science.gov (United States)

    Lee, George

    2014-11-03

    Exercise-induced rhabdomyolysis, or exertional rhabdomyolysis (ER), is a clinical entity typically considered when someone presents with muscle stiffness, swelling, and pain out of proportion to the expected fatigue post exercise. The diagnosis is confirmed by myoglobinuria, and an elevated serum Creatinine Phosphokinase (CPK) level, usually 10 times the normal range. However, an elevation in CPK is seen in most forms of strenuous exercise, up to 20 times the upper normal range. Therefore, there is no definitive pathologic CPK cut-off. Fortunately the dreaded complication of acute renal failure is rare compared to other forms rhabdomyolysis. We review the risks, diagnosis, clinical course and treatment for exercise- induced rhabdomyolysis.

  6. Migraine induced by hypoxia

    DEFF Research Database (Denmark)

    Arngrim, Nanna; Schytz, Henrik Winther; Britze, Josefine

    2016-01-01

    in the visual cortex were measured by proton magnetic resonance spectroscopy. The circumference of cranial arteries was measured by 3 T high-resolution magnetic resonance angiography. Hypoxia induced migraine-like attacks in eight patients compared to one patient after sham (P = 0.039), aura in three...... and possible aura in 4 of 15 patients. Hypoxia did not change glutamate concentration in the visual cortex compared to sham, but increased lactate concentration (P = 0.028) and circumference of the cranial arteries (P ... suggests that hypoxia may provoke migraine headache and aura symptoms in some patients. The mechanisms behind the migraine-inducing effect of hypoxia should be further investigated....

  7. Airbag induced corneal ectasia.

    Science.gov (United States)

    Mearza, Ali A; Koufaki, Fedra N; Aslanides, Ioannis M

    2008-02-01

    To report a case of airbag induced corneal ectasia. Case report. A patient 3 years post-LASIK developed bilateral corneal ectasia worse in the right eye following airbag deployment in a road traffic accident. At last follow up, best corrected vision was 20/40 with -4.00/-4.00 x 25 in the right eye and 20/25 with -1.25/-0.50 x 135 in the left eye. This is a rare presentation of trauma induced ectasia in a patient post-LASIK. It is possible that reduction in biomechanical integrity of the cornea from prior refractive surgery contributed to this presentation.

  8. Sleep-inducing factors.

    Science.gov (United States)

    García-García, Fabio; Acosta-Peña, Eva; Venebra-Muñoz, Arturo; Murillo-Rodríguez, Eric

    2009-08-01

    Kuniomi Ishimori and Henri Piéron were the first researchers to introduce the concept and experimental evidence for a chemical factor that would presumably accumulate in the brain during waking and eventually induce sleep. This substance was named hypnotoxin. Currently, the variety of substances which have been shown to alter sleep includes peptides, cytokines, neurotransmitters and some substances of lipidic nature, many of which are well known for their involvement in other biological activities. In this chapter, we describe the sleep-inducing properties of the vasoactive intestinal peptide, prolactin, adenosine and anandamide.

  9. The efficacy of dexamethasone reducing postoperative pain and emesis after total knee arthroplasty: A systematic review and meta-analysis.

    Science.gov (United States)

    Fan, Zhengrui; Ma, Jianxiong; Kuang, Mingjie; Zhang, Lukai; Han, Biao; Yang, Baocheng; Wang, Ying; Ma, Xinlong

    2018-04-01

    Total knee arthroplasty (TKA) is gradually emerging as the treatment of choice for end-stage osteoarthritis. In the past, Perioperative dexamethasone treatment is still a controversial subject in total knee arthroplasty. Therefore, we write this systematic review and meta-analysis to evaluate the efficacy of dexamethasone on pain and recovery after Total knee Arthroplasty. Embase, Pubmed, and Cochrane Library were comprehensively searched. Randomized controlled trials, cohort studies were included in our meta-analysis. Eight studies that compared dexamethasone groups with placebo groups were included in our meta-analysis. The research was reported according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Randomized controlled trials were included in our meta-analysis. Our study demonstrated that the dexamethasone group was more effective than the placebo group in term of VAS score at 24 h(P meta-analysis demonstrated that dexamethasone decreased postoperative pain, the incidence of POVN, and total opioid consumption effectively which played a critical role in rapid recovery to TKA. However, we still need large sample size, high quality studies to explore the relationship between complications and dose response to give the final conclusion. Copyright © 2018. Published by Elsevier Ltd.

  10. Comparison of Antiemetic Effects of Ondansetron, Granisetron and Tropisetron in Treatment of Acute Emesis Caused By Cisplatin/Paclitaxel Chemotherapy

    Directory of Open Access Journals (Sweden)

    Taner Turan

    2016-06-01

    CONCLUSION: Although this study is not prospective, it is homogenous for treatment modalities and patient selection. Complete response was observed in 63% of courses; however this antiemetic affect is not found to be satisfactory. In order to develope better protocols there is need for prospective studies on homogenous group. Antiemetic efficiency has to associate for chemotherapy protocols.

  11. 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.

    Science.gov (United States)

    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

  12. Inducible laryngeal obstruction

    DEFF Research Database (Denmark)

    Halvorsen, Thomas; Walsted, Emil Schwarz; Bucca, Caterina

    2017-01-01

    Inducible laryngeal obstruction (ILO) describes an inappropriate, transient, reversible narrowing of the larynx in response to external triggers. ILO is an important cause of a variety of respiratory symptoms and can mimic asthma. Current understanding of ILO has been hampered by imprecise nomenc...

  13. Drug-induced apnea.

    Science.gov (United States)

    Boutroy, M J

    1994-01-01

    Drugs have been in the past and will in the future still be liable to induce apnea in neonates, infants and older children. At these different stages of development, the child may be abnormally vulnerable to respiratory disorders and apnea, and doses of drugs, without any abnormal side effects in adult patients, can be harmful in younger subjects. Drugs responsible for apnea during development are numerous, but more than half of the problems are induced by sedatives and hypnotics, among which phenothiazines, barbiturates, benzodiazepines (included transplacentally acquired) and general anesthetics are a few. Other pharmacological families are apnea inducers in the neonatal period and childhood: analgesics and opioid narcotics, agents acting at the levels of neuromuscular function and autonomic ganglia, and cardiovascular agents. The pathogenesis of these apneas depends on the disturbance of any mechanism responsible for the respiratory activity: medullary centers and brain stem structures, afferent influx to CNS, sleep stages, upper airways, lungs and respiratory muscles. At key stages such as birth and infancy, drugs may emphasize the particular sensitivity of the mechanisms responsible for inducing apnea. This might explain unexpected respiratory disorders during development.

  14. Metronidazole-Induced Pancreatitis

    Directory of Open Access Journals (Sweden)

    E. O'Halloran

    2010-01-01

    Conclusion. This case provides the eighth report of Metronidazole induced pancreatitis. All of the cases were reported in females and ran a benign course.Early diagnosis, discontinuation of the drug and supportive care will lead to a successful recovery in the majority of cases.

  15. XTC-induced hepatitis

    NARCIS (Netherlands)

    Oranje, W.A.; van Pol, V.; van der Wurff, A.A.; Zeijen, R.N.; Stockbrügger, R.W.; Arends, J.W.

    1994-01-01

    XTC-induced hepatitis. Oranje WA, von Pol P, vd Wurff A, Zeijen RN, Stockbrugger RW, Arends JW. Department of Internal Medicine, University Hospital, Maastricht, Netherlands. An increasing number of severe complications associated with the use of XTC is being reported. After 11 earlier case reports

  16. Bowthruster-induced damage

    NARCIS (Netherlands)

    Schokking, L.A.; Janssen, P.C.; Verhagen, H.J.

    2003-01-01

    The stability of stones in propeller-induced jet wash is still difficult to predict. Especially the trend of bowthrusters increasing in size and power in sea going ships (especially ferries) over the last years may be a reason for concern when dealing with the protection of slopes and beds. But also

  17. Muon-induced fission

    International Nuclear Information System (INIS)

    Polikanov, S.

    1980-01-01

    A review of recent experimental results on negative-muon-induced fission, both of 238 U and 232 Th, is given. Some conclusions drawn by the author are concerned with muonic atoms of fission fragments and muonic atoms of the shape isomer of 238 U. (author)

  18. Calotropis procera -induced keratitis

    Directory of Open Access Journals (Sweden)

    Pandey Nidhi

    2009-01-01

    Full Text Available Calotropis procera produces copious amounts of latex, which has been shown to possess several pharmacological properities. Its local application produces intense inflammatory response. In the 10 cases of Calotropis procera -induced keratitis reported here, the clinical picture showed corneal edema with striate keratopathy without any evidence of intraocular inflammation. The inflammation was reversed by the local application of steroid drops.

  19. Induced nuclear beta decay

    International Nuclear Information System (INIS)

    Reiss, H.R.

    1986-01-01

    Certain nuclear beta decay transitions normally inhibited by angular momentum or parity considerations can be induced to occur by the application of an electromagnetic field. Such decays can be useful in the controlled production of power, and in fission waste disposal

  20. Hyperthermia-induced apoptosis

    NARCIS (Netherlands)

    Nijhuis, E.H.A.

    2008-01-01

    This thesis describes a number of studies that investigated several aspects of heat-induced apoptosis in human lymphoid malignancies. Cells harbour both pro- and anti-apoptotic proteins and the balance between these proteins determines whether a cell is susceptible to undergo apoptosis. In this

  1. Drug induced aseptic meningitis

    African Journals Online (AJOL)

    PROF. EZECHUKWU

    2013-09-29

    Sep 29, 2013 ... Abstract. Drug-induced aseptic meningitis (DIAM) is a rare but important and often challenging diagnosis for the physician. Intake of antimicrobials, steroids, anal- gesics amongst others has been implicated. Signs and symptoms generally develop within 24-48 hours of drug ingestion. The pa- tient often ...

  2. Contrast induced nephropathy

    DEFF Research Database (Denmark)

    Stacul, Fulvio; van der Molen, Aart J; Reimer, Peter

    2011-01-01

    PURPOSE: The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 1999 guidelines on contrast medium-induced nephropathy (CIN). AREAS COVERED: Topics reviewed include the definition of CIN, the choice of contrast medium, the prophylactic me...

  3. Radiation-induced pneumothorax

    International Nuclear Information System (INIS)

    Epstein, D.M.; Littman, P.; Gefter, W.B.; Miller, W.T.; Raney, R.B. Jr.

    1983-01-01

    Pneumothorax is an uncommon complication of radiation therapy to the chest. The proposed pathogenesis is radiation-induced fibrosis promoting subpleural bleb formation that ruptures resulting in pneumothorax. We report on two young patients with primary sarcomas without pulmonary metastases who developed spontaneous pneumothorax after irradiation. Neither patient had antecedent radiographic evidence of pulmonary fibrosis

  4. Irradiation-Induced Nanostructures

    Energy Technology Data Exchange (ETDEWEB)

    Birtcher, R.C.; Ewing, R.C.; Matzke, Hj.; Meldrum, A.; Newcomer, P.P.; Wang, L.M.; Wang, S.X.; Weber, W.J.

    1999-08-09

    This paper summarizes the results of the studies of the irradiation-induced formation of nanostructures, where the injected interstitials from the source of irradiation are not major components of the nanophase. This phenomena has been observed by in situ transmission electron microscopy (TEM) in a number of intermetallic compounds and ceramics during high-energy electron or ion irradiations when the ions completely penetrate through the specimen. Beginning with single crystals, electron or ion irradiation in a certain temperature range may result in nanostructures composed of amorphous domains and nanocrystals with either the original composition and crystal structure or new nanophases formed by decomposition of the target material. The phenomenon has also been observed in natural materials which have suffered irradiation from the decay of constituent radioactive elements and in nuclear reactor fuels which have been irradiated by fission neutrons and other fission products. The mechanisms involved in the process of this nanophase formation are discussed in terms of the evolution of displacement cascades, radiation-induced defect accumulation, radiation-induced segregation and phase decomposition, as well as the competition between irradiation-induced amorphization and recrystallization.

  5. Lupus induced by medicaments

    International Nuclear Information System (INIS)

    Canas D, Carlos Alberto; Perafan B, Pablo Eduardo

    2001-01-01

    We describe a 55 years old female patient who consulted by fever syndrome, artralgias and the presence of high tittles positives antinuclear antibodies. She had arterial hypertension in treatment with captopril. We suspected the clinical diagnoses of drug-induced lupus; the withdraw of captopril was associated with the remission of the clinical and laboratory manifestations

  6. Glucocorticoid-induced hyperglycaemia

    NARCIS (Netherlands)

    Gerards, M.C.

    2018-01-01

    This thesis contains studies on current practice, clinical implications and treatment of excess glucocorticoid receptor (GCR) stimulation, with a focus on glucocorticoid-induced hyperglycaemia (GCIH). Chapter 1 is a general introduction to the glucocorticoid hormone. In chapter 2 , we have

  7. Understanding induced seismicity

    NARCIS (Netherlands)

    Elsworth, Derek; Spiers, Christopher J.|info:eu-repo/dai/nl/304829323; Niemeijer, Andre R.|info:eu-repo/dai/nl/370832132

    2016-01-01

    Fluid injection–induced seismicity has become increasingly widespread in oil- and gas-producing areas of the United States (1–3) and western Canada. It has shelved deep geothermal energy projects in Switzerland and the United States (4), and its effects are especially acute in Oklahoma, where

  8. Geomagnetism and Induced Voltage

    Science.gov (United States)

    Abdul-Razzaq, W.; Biller, R. D.

    2010-01-01

    Introductory physics laboratories have seen an influx of "conceptual integrated science" over time in their classrooms with elements of other sciences such as chemistry, biology, Earth science, and astronomy. We describe a laboratory to introduce this development, as it attracts attention to the voltage induced in the human brain as it…

  9. INDUCED ABORTION IN NIGERIA

    African Journals Online (AJOL)

    2014-06-01

    Jun 1, 2014 ... 95% of women would have had an induced abortion. (10), which ... who were fluent in both English and the local language were chosen ... the woman and society. The Muslims ... that “traditional methods are only effective at the early stages of ... modern and traditional family planning services. However ...

  10. Advertising-Induced Embarrassment

    NARCIS (Netherlands)

    Puntoni, S.; Hooge, de I.E.; Verbeke, W.J.M.I.

    2015-01-01

    Abstract Consumer embarrassment is a concern for many advertisers. Yet little is known about ad-induced embarrassment. The authors investigate when and why consumers experience embarrassment as a result of exposure to socially sensitive advertisements. The theory distinguishes between viewing

  11. Neutrophil derived LTB4 induces macrophage aggregation in response to encapsulated Streptococcus iniae infection.

    Directory of Open Access Journals (Sweden)

    William J B Vincent

    Full Text Available Immune cells sense and react to a multitude of factors including both host and microbe-derived signals. Understanding how cells translate these cues into particular cellular behaviors is a complex yet critical area of study. We have previously shown that both neutrophils and macrophages are important for controlling the fish pathogen Streptococcus iniae. Here, we report both host and bacterial determinants leading to the formation of organized macrophage aggregates as part of the host inflammatory response in a subset of infected larvae. Streptococcal capsule was a required signal for aggregate formation. Macrophage aggregation coincided with NFκB activity, and the formation of these aggregates is mediated by leukotriene B4 (LTB4 produced by neutrophils. Depletion, inhibition, or genetic deletion of leukotriene A4 hydrolase (Lta4h, which catalyzes the last step in LTB4 synthesis, resulted in the absence of macrophage aggregation. Larvae with impaired neutrophil function also had impaired macrophage aggregation; however, aggregate formation was partially rescued with the addition of exogenous LTB4. Neutrophil-specific expression of lta4h was sufficient to rescue macrophage aggregation in Lta4h-deficient larvae and increased host survival following infection. In summary, our findings highlight a novel innate immune response to infection in which specific bacterial products drive neutrophils that modulate macrophage behavior through eicosanoid signaling.

  12. Uterine contraction induced by Tanzanian plants used to induce abortion

    DEFF Research Database (Denmark)

    Nikolajsen, Tine; Nielsen, Frank; Rasch, Vibeke

    2011-01-01

    Women in Tanzania use plants to induce abortion. It is not known whether the plants have an effect.......Women in Tanzania use plants to induce abortion. It is not known whether the plants have an effect....

  13. [Hydroxyurea-induced pneumonia].

    Science.gov (United States)

    Girard, A; Ricordel, C; Poullot, E; Claeyssen, V; Decaux, O; Desrues, B; Delaval, P; Jouneau, S

    2014-05-01

    Hydroxyurea is an antimetabolite drug used in the treatment of myeloproliferative disorders. Common adverse effects include haematological, gastrointestinal cutaneous manifestations, and fever. Hydroxyurea-induced pneumonitis is unusual. A female patient was treated with hydroxyurea for polycythemia vera. She was admitted 20 days after commencing treatment with a high fever, productive cough, clear sputum and nausea. A chest CT-scan showed diffuse ground-glass opacities. Microbiological investigations were negative. The symptoms disappeared a few days after discontinuation of the drug and rechallenge led to a relapse of symptoms. Our case and 15 earlier cases of hydroxyurea-induced pneumonitis are reviewed. Two patterns of this disease may exist: an acute febrile form occurring within 1 month of introduction of hydroxyurea and a subacute form without fever. Even if uncommon, one should be aware of this complication of hydroxyurea. Copyright © 2013. Published by Elsevier Masson SAS.

  14. Hydroxychloroquine-induced erythroderma.

    Science.gov (United States)

    Pai, Sunil B; Sudershan, Bhuvaneshwari; Kuruvilla, Maria; Kamath, Ashwin; Suresh, Pooja K

    2017-01-01

    Erythroderma is characterized by diffuse erythema and scaling of the skin involving more than 90% of the total body skin surface area. Drug-induced erythroderma has rarely been reported with hydroxychloroquine. We report a case of a 50-year-old female patient, with systemic lupus erythematosus, who developed itchy lesions all over the body 1 month after starting treatment with hydroxychloroquine. Drug-induced erythroderma was suspected. Hydroxychloroquine was withdrawn and the patient was treated with emollients, mid-potency corticosteroids, and oral antihistamines. A biopsy was done which confirmed the diagnosis of erythroderma. She recovered with treatment and was discharged. A careful history and clinical examination to search for potential causative factors will help prevent disabling sequelae in erythroderma.

  15. Mild induced hypothermia

    DEFF Research Database (Denmark)

    Johansen, Maria E; Jensen, Jens-Ulrik; Bestle, Morten H

    2014-01-01

    INTRODUCTION: Coagulopathy associates with poor outcome in sepsis. Mild induced hypothermia has been proposed as treatment in sepsis but it is not known whether this intervention worsens functional coagulopathy. MATERIALS AND METHODS: Interim analysis data from an ongoing randomized controlled...... trial; The Cooling And Surviving Septic shock (CASS) study. Patients suffering severe sepsis/septic shock are allocated to either mild induced hypothermia (cooling to 32-34°C for 24hours) or control (uncontrolled temperature). TRIAL REGISTRATION: NCT01455116. Thrombelastography (TEG) is performed three....... At enrollment, 3%, 38%, and 59% had a hypocoagulable, normocoagulable, and hypercoagulable TEG clot strength (MA), respectively. In the hypothermia group, functional coagulopathy improved during the hypothermia phase, measured by R and MA, in patients with hypercoagulation as well as in patients...

  16. Time Domain Induced Polarization

    DEFF Research Database (Denmark)

    Fiandaca, Gianluca; Auken, Esben; Christiansen, Anders Vest

    2012-01-01

    Time-domain-induced polarization has significantly broadened its field of reference during the last decade, from mineral exploration to environmental geophysics, e.g., for clay and peat identification and landfill characterization. Though, insufficient modeling tools have hitherto limited the use...... of time-domaininduced polarization for wider purposes. For these reasons, a new forward code and inversion algorithm have been developed using the full-time decay of the induced polarization response, together with an accurate description of the transmitter waveform and of the receiver transfer function......, to reconstruct the distribution of the Cole-Cole parameters of the earth. The accurate modeling of the transmitter waveform had a strong influence on the forward response, and we showed that the difference between a solution using a step response and a solution using the accurate modeling often is above 100...

  17. Topiramate Induced Excessive Sialorrhea

    Directory of Open Access Journals (Sweden)

    Ersel Dag

    2015-11-01

    Full Text Available It is well-known that drugs such as clozapine and lithium can cause sialorrhea. On the other hand, topiramate has not been reported to induce sialorrhea. We report a case of a patient aged 26 who was given antiepileptic and antipsychotic drugs due to severe mental retardation and intractable epilepsy and developed excessive sialorrhea complaint after the addition of topiramate for the control of seizures. His complaints continued for 1,5 years and ended after giving up topiramate. We presented this case since it was a rare sialorrhea case induced by topiramate. Clinicians should be aware of the possibility of sialorrhea development which causes serious hygiene and social problems when they want to give topiramate to the patients using multiple drugs.

  18. Noise-Induced Hearing Loss

    Science.gov (United States)

    ... Home » Health Info » Hearing, Ear Infections, and Deafness Noise-Induced Hearing Loss On this page: What is ... I find additional information about NIHL? What is noise-induced hearing loss? Every day, we experience sound ...

  19. Induced quantum torsion

    International Nuclear Information System (INIS)

    Denardo, G.; Spallucci, E.

    1985-07-01

    We study pregeometry in the framework of a Poincare gauge field theory. The Riemann-Cartan space-time is shown to be an ''effective geometry'' for this model in the low energy limit. By using Heat Kernel techniques we find the induced action for curvature and torsion. We obtain in this way the usual Einstein-Hilbert action plus an axial Maxwell term describing the propagation of a massless, axial vector torsion field. (author)

  20. Cisplatin Induced Nephrotoxicity

    Directory of Open Access Journals (Sweden)

    Seyed Seifollah Beladi Mousavi

    2014-02-01

    The standard approach to prevent cisplatin-induced nephrotoxicity is the administration of lower doses of cisplatin in combination with the administration of full intravenous isotonic saline before and after cisplatin administration. Although a number of pharmacologic agents including sodium thiosulfate, N-acetylcysteine, theophylline and glycine have been evaluated for prevention of nephrotoxicity, none have proved to have an established role, thus, additional clinical studies will be required to confirm their probable effects.

  1. Amitriptyline induced cervical dystonia

    Directory of Open Access Journals (Sweden)

    Shivanand B Hiremath

    2016-01-01

    Full Text Available Tricyclic antidepressants (TCAs, such as amitriptyline, have many side effects. But extrapyramidal tract symptom is an uncommon side effect of these drugs. Here, we report a case of a 28-year-old male who is suffering from amitriptyline induced cervical dystonia. Though rare, this side effect is an uncomfortable condition and may influence drug compliance. So clinicians should be aware of this side effect while treating a patient with amitriptyline.

  2. Polycation induced actin bundles

    OpenAIRE

    Muhlrad, Andras; Grintsevich, Elena E.; Reisler, Emil

    2011-01-01

    Three polycations, polylysine, the polyamine spermine and the polycationic protein lysozyme were used to study the formation, structure, ionic strength sensitivity and dissociation of polycation-induced actin bundles. Bundles form fast, simultaneously with the polymerization of MgATP-G-actins, upon addition of polycations to solutions of actins at low ionic strength conditions. This indicates that nuclei and/or nascent filaments bundle due to attractive, electrostatic effect of polycations an...

  3. Induced current heating probe

    International Nuclear Information System (INIS)

    Thatcher, G.; Ferguson, B.G.; Winstanley, J.P.

    1984-01-01

    An induced current heating probe is of thimble form and has an outer conducting sheath and a water flooded flux-generating unit formed from a stack of ferrite rings coaxially disposed in the sheath. The energising coil is made of solid wire which connects at one end with a coaxial water current tube and at the other end with the sheath. The stack of ferrite rings may include non-magnetic insulating rings which help to shape the flux. (author)

  4. Induced QCD I: theory

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, Bastian B. [Institute for Theoretical Physics, Goethe-University of Frankfurt,60438 Frankfurt (Germany); Institute for Theoretical Physics, University of Regensburg,93040 Regensburg (Germany); Lohmayer, Robert; Wettig, Tilo [Institute for Theoretical Physics, University of Regensburg,93040 Regensburg (Germany)

    2016-11-14

    We explore an alternative discretization of continuum SU(N{sub c}) Yang-Mills theory on a Euclidean spacetime lattice, originally introduced by Budzcies and Zirnbauer. In this discretization the self-interactions of the gauge field are induced by a path integral over N{sub b} auxiliary boson fields, which are coupled linearly to the gauge field. The main progress compared to earlier approaches is that N{sub b} can be as small as N{sub c}. In the present paper we (i) extend the proof that the continuum limit of the new discretization reproduces Yang-Mills theory in two dimensions from gauge group U(N{sub c}) to SU(N{sub c}), (ii) derive refined bounds on N{sub b} for non-integer values, and (iii) perform a perturbative calculation to match the bare parameter of the induced gauge theory to the standard lattice coupling. In follow-up papers we will present numerical evidence in support of the conjecture that the induced gauge theory reproduces Yang-Mills theory also in three and four dimensions, and explore the possibility to integrate out the gauge fields to arrive at a dual formulation of lattice QCD.

  5. Laser induced energy transfer

    International Nuclear Information System (INIS)

    Falcone, R.W.

    1979-01-01

    Two related methods of rapidly transferring stored energy from one excited chemical species to another are described. The first of these, called a laser induced collision, involves a reaction in which the energy balance is met by photons from an intense laser beam. A collision cross section of ca 10 - 17 cm 2 was induced in an experiment which demonstrated the predicted dependence of the cross section on wavelength and power density of the applied laser. A second type of laser induced energy transfer involves the inelastic scattering of laser radiation from energetically excited atoms, and subsequent absorption of the scattered light by a second species. The technique of producing the light, ''anti-Stokes Raman'' scattering of visible and infrared wavelength laser photons, is shown to be an efficient source of narrow bandwidth, high brightness, tunable radiation at vacuum ultraviolet wavelengths by using it to excite a rare gas transition at 583.7 A. In addition, this light source was used to make the first measurement of the isotopic shift of the helium metastable level at 601 A. Applications in laser controlled chemistry and spectroscopy, and proposals for new types of lasers using these two energy transfer methods are discussed

  6. Radiation-induced myelopathy

    Energy Technology Data Exchange (ETDEWEB)

    Gaenshirt, H [Heidelberg Univ. (F.R. Germany). Neurologische Klinik

    1975-10-01

    12 cases of radiation-induced myelopathy after /sup 60/Co teletherapy are reported on. Among these were 10 thoracal lesions, one cerviothoracal lesion, and one lesion of the medulla oblongata. In 9 cases, Hodgkin's disease had been the primary disease, tow patients had been irradiated because of suspected vertebral metastases of cancer of the breast, and one patient had suffered from a glomus tumour of the petrous bone. The spinal doses had exceeded the tolerance doses recommended in the relevant literature. There was no close correlation between the radiation dose and the course of the disease. The latency periods between the end of the radiotherapy and the onset of the neurological symptons varied from 6 to 16 mouths and were very constant in 7 cases with 6 to 9 months. The segmental height of the lesion corresponded to the level of irradiation. The presenting symptons of radiation-induced myelopathy are buruing dysaesthesias and Brown-Sequard's paralysis which may develop into transverse lesion of the cord with paraplegia still accompanied by dissociated perception disorders. The disease developed intermittently. Disturbances of the bladder function are frequent. The fluid is normal in most cases. Myelographic examinations were made in 8 cases. 3 cases developed into stationary cases exhibiting. Brown-Sequard syndrome, while 9 patients developed transverse lesion of the cord with paraplegia. 3 patients have died; antopsy findings are given for two of these. In the pathogenesis of radiation-induced myelopathy, the vascular factor is assumed to be of decisive importance.

  7. Baby universes with induced gravity

    International Nuclear Information System (INIS)

    Gao Yihong; Gao Hongbo

    1989-01-01

    In this paper some quantum effects of baby universes with induced gravity are discussed. It is proved that the interactions between the baby-parent universes are non-local, and argue that the induced low-energy cosmological constant is zero. This argument does not depend on the detail of the induced potential

  8. 2016 updated MASCC/ESMO consensus recommendations

    DEFF Research Database (Denmark)

    Roila, Fausto; Warr, David; Hesketh, Paul J

    2017-01-01

    PURPOSE: An update of the recommendations for the prophylaxis of acute and delayed emesis induced by moderately emetogenic chemotherapy published after the last MASCC/ESMO antiemetic consensus conference in 2009 has been carried out. METHODS: A systematic literature search using PubMed from Janua...

  9. Osteonecrosis in patients with testicular tumours treated with chemotherapy.

    NARCIS (Netherlands)

    Berkmortel, F.W.P.J. van den; Wit, R. de; Rooy, J.W.J. de; Mulder, P.H.M. de

    2004-01-01

    The role of antiemetics is invaluable in allowing cancer patients to complete, otherwise possibly intolerable, chemotherapy. In the Perugia Consensus Conference it was decided that the recommended antiemetic regimen in the prevention of acute emesis induced by a single high, low and repeated doses

  10. Polycation induced actin bundles.

    Science.gov (United States)

    Muhlrad, Andras; Grintsevich, Elena E; Reisler, Emil

    2011-04-01

    Three polycations, polylysine, the polyamine spermine and the polycationic protein lysozyme were used to study the formation, structure, ionic strength sensitivity and dissociation of polycation-induced actin bundles. Bundles form fast, simultaneously with the polymerization of MgATP-G-actins, upon the addition of polycations to solutions of actins at low ionic strength conditions. This indicates that nuclei and/or nascent filaments bundle due to attractive, electrostatic effect of polycations and the neutralization of repulsive interactions of negative charges on actin. The attractive forces between the filaments are strong, as shown by the low (in nanomolar range) critical concentration of their bundling at low ionic strength. These bundles are sensitive to ionic strength and disassemble partially in 100 mM NaCl, but both the dissociation and ionic strength sensitivity can be countered by higher polycation concentrations. Cys374 residues of actin monomers residing on neighboring filaments in the bundles can be cross-linked by the short span (5.4Å) MTS-1 (1,1-methanedyl bismethanethiosulfonate) cross-linker, which indicates a tight packing of filaments in the bundles. The interfilament cross-links, which connect monomers located on oppositely oriented filaments, prevent disassembly of bundles at high ionic strength. Cofilin and the polysaccharide polyanion heparin disassemble lysozyme induced actin bundles more effectively than the polylysine-induced bundles. The actin-lysozyme bundles are pathologically significant as both proteins are found in the pulmonary airways of cystic fibrosis patients. Their bundles contribute to the formation of viscous mucus, which is the main cause of breathing difficulties and eventual death in this disorder. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Induced mutations in citrus

    International Nuclear Information System (INIS)

    Spiegel-Roy, P.; Vardi, Aliza

    1990-01-01

    Full text: Parthenocarpic tendency is an important prerequisite for successful induction of seedlessness in breeding and especially in mutation breeding. A gene for asynapsis and accompanying seedless fruit has been found by us in inbred progeny of cv. 'Wilking'. Using budwood irradiation by gamma rays, seedless mutants of 'Eureka' and 'Villafranca' lemon (original clone of the latter has 25 seeds) and 'Minneola' tangelo have been obtained. Ovule sterility of the three mutants is nearly complete, with some pollen fertility still remaining. A semi-compact mutant of Shamouti orange has been obtained by irradiation. A programme for inducing seedlessness in easy peeling citrus varieties and selections has been initiated. (author)

  12. Shear-induced chaos

    International Nuclear Information System (INIS)

    Lin, Kevin K; Young, Lai-Sang

    2008-01-01

    Guided by a geometric understanding developed in earlier works of Wang and Young, we carry out numerical studies of shear-induced chaos in several parallel but different situations. The settings considered include periodic kicking of limit cycles, random kicks at Poisson times and continuous-time driving by white noise. The forcing of a quasi-periodic model describing two coupled oscillators is also investigated. In all cases, positive Lyapunov exponents are found in suitable parameter ranges when the forcing is suitably directed

  13. Shear-induced chaos

    Science.gov (United States)

    Lin, Kevin K.; Young, Lai-Sang

    2008-05-01

    Guided by a geometric understanding developed in earlier works of Wang and Young, we carry out numerical studies of shear-induced chaos in several parallel but different situations. The settings considered include periodic kicking of limit cycles, random kicks at Poisson times and continuous-time driving by white noise. The forcing of a quasi-periodic model describing two coupled oscillators is also investigated. In all cases, positive Lyapunov exponents are found in suitable parameter ranges when the forcing is suitably directed.

  14. Xerostomia induced by radiotherapy

    Directory of Open Access Journals (Sweden)

    Alimi D

    2015-08-01

    Full Text Available David Alimi Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USAWe read with great interest the excellent review on xerostomia induced by radiotherapy, by Pinna et al.1 The authors should be congratulated for a very detailed review of the physiopathology, clinical symptoms, and therapeutic management of an extremely difficult condition. Although we agree that the use of anticholinergic medication represents treatment, it requires the patient to have residual salivary gland function. Unfortunately, it is well established that in most cases radiotherapy destroys most of the salivary gland and associated salivary secretions.     

  15. Cannabis induced asystole.

    Science.gov (United States)

    Brancheau, Daniel; Blanco, Jessica; Gholkar, Gunjan; Patel, Brijesh; Machado, Christian

    2016-01-01

    Cannabis or marijuana is the most used recreational, and until recently illegal, drug in the United States. Although cannabis has medicinal use, its consumption has been linked to motor vehicle accidents in dose dependent fashion. Marijuana and other cannabinoids produce a multitude of effects on the human body that may result in these motor vehicle accidents. Some of the effects that marijuana has been known to cause include altered sensorium, diminished reflexes, and increased vagal tone. We present a case of cannabis induced asystole from hypervagotonia. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Pacing-induced Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Alex Koo

    2017-10-01

    Full Text Available We present a case of pacing-induced cardiomyopathy. The patient presented with clinical symptoms of dyspnea, leg swelling, and orthopnea several months after a dual-chambered pacemaker was placed for third-degree heart block. The echocardiogram demonstrated a depressed ejection fraction. Coronary angiography was performed, which showed widely patent vessels. Single- and dual-chambered pacemakers create ventricular dyssynchrony, which in turn can cause structural, molecular changes leading to cardiomyopathy. With early intervention of biventricular pacemaker replacement, these changes can be reversible; thus, a timely diagnosis and awareness is warranted.

  17. Induced skeletal mutations

    International Nuclear Information System (INIS)

    Selby, P.B.

    1979-01-01

    This paper describes a large-scale experiment that, by means of breeding tests, confirmed that many dominant skeletal mutations are induced by large-dose radiation exposure. The author also discusses: (1) the major advantages and disadvantages of the skeletal method in improving estimates of genetic hazard to man; (2) future uses of the skeletal method; (3) direct estimation of risk beyond the first generation using the skeletal method; and (4) the possibility of using the skeletal method as a quick and easy screen for chemical mutagens

  18. Trauma Induced Coagulopathy

    DEFF Research Database (Denmark)

    Genét, Gustav Folmer; Johansson, Per; Meyer, Martin Abild Stengaard

    2013-01-01

    It remains debated whether traumatic brain injury (TBI) induces a different coagulopathy compared to non-TBI. This study investigated traditional coagulation tests, biomarkers of coagulopathy and endothelial damage in trauma patients with and without TBI. Blood from 80 adult trauma patients were...... sampled (median of 68 min (IQR 48-88) post-injury) upon admission to our trauma centre. Plasma/serum were retrospectively analysed for biomarkers reflecting sympathoadrenal activation (adrenaline, noradrenaline), coagulation activation/inhibition and fibrinolysis (protein C, activated protein C, tissue...

  19. Trastuzumab-induced cardiomyopathy.

    Science.gov (United States)

    Guglin, Maya; Cutro, Raymond; Mishkin, Joseph D

    2008-06-01

    Trastuzumab is a recombinant humanized monoclonal antibody used for the treatment of advanced breast cancer. It improves survival and increases response to chemotherapy. The major side effect of trastuzumab is cardiotoxicity manifesting as a reduction in left ventricular systolic function, either asymptomatic or with signs and symptoms of heart failure. Although reversible in most cases, cardiotoxicity frequently results in the discontinuation of trastuzumab. The objective of this review is to summarize facts about trastuzumab-induced cardiotoxicity and to highlight the areas of future investigations. We searched PubMed for trials involving trastuzumab used as an adjuvant therapy for breast cancer, including the metastatic breast cancer setting, and focused on cardiotoxicity.

  20. Docetaxel-induced neuropathy

    DEFF Research Database (Denmark)

    Eckhoff, Lise; Feddersen, Søren; Knoop, Ann

    2015-01-01

    Background. Docetaxel is a highly effective treatment of a wide range of malignancies but is often associated with peripheral neuropathy. The genetic variability of genes involved in the transportation or metabolism of docetaxel may be responsible for the variation in docetaxel-induced peripheral...... neuropathy (DIPN). The main purpose of this study was to investigate the impact of genetic variants in GSTP1 and ABCB1 on DIPN. Material and methods. DNA was extracted from whole blood from 150 patients with early-stage breast cancer who had received adjuvant docetaxel from February 2011 to May 2012. Two...

  1. Chemotherapy-induced polyneuropathy

    DEFF Research Database (Denmark)

    Zedan, Ahmed; Vilholm, Ole Jakob

    2014-01-01

    Chemotherapy-induced polyneuropathy (CIPN) is a common, but underestimated, clinical challenge. Incidence varies depending on many factors that are equally as important as the type of chemotherapeutic agent itself. Moreover, the assessment of CIPN is still uncertain, as several of the most...... frequently used scales do not rely on a formal neurological evaluation and depend on patients' reports and examiners' interpretations. Therefore, the aim of this MiniReview was to introduce the most common chemotherapies that cause neuropathy, and in addition to this, highlight the most significant...

  2. Contrast induced nephropathy

    DEFF Research Database (Denmark)

    Stacul, Fulvio; van der Molen, Aart J; Reimer, Peter

    2011-01-01

    PURPOSE: The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 1999 guidelines on contrast medium-induced nephropathy (CIN). AREAS COVERED: Topics reviewed include the definition of CIN, the choice of contrast medium, the prophylactic me....../min/1.73 m (2) is CIN risk threshold for intravenous contrast medium. • Hydration with either saline or sodium bicarbonate reduces CIN incidence. • Patients with eGFR = 60 ml/min/1.73 m (2) receiving contrast medium can continue metformin normally....

  3. Ion induced Auger spectroscopy

    International Nuclear Information System (INIS)

    Thomas, E.W.; Legg, K.O.; Metz, W.A.

    1980-01-01

    Auger electron spectra are induced by impact of heavy ions (e.g. Ar + ) on surfaces; it has been suggested that analysis of such spectra would be a useful technique for surface analysis. We have examined the Auger spectra for various projectile-target combinations and present as representative data the spectra for 100 keV Ar + impact on Al, Cr, Mn, Fe and Co. For a projectile incident on a species of higher nuclear charge the spectrum is dominated by Auger lines from the projectile, broadened considerably by the Doppler effect due to the projectile's motion. The spectra are not characteristic of the target and therefore offer no opportunity for surface analysis. For a projectile incident on a target of lower nuclear charge the spectrum is that of the target species but the spectrum is consistent with the source being sputtered excited atoms; the Auger electrons do not come from the surface. We conclude that the ion induced Auger spectra are in general not a convenient method for surface analysis. (orig.)

  4. Induced Seismicity Monitoring System

    Science.gov (United States)

    Taylor, S. R.; Jarpe, S.; Harben, P.

    2014-12-01

    There are many seismological aspects associated with monitoring of permanent storage of carbon dioxide (CO2) in geologic formations. Many of these include monitoring underground gas migration through detailed tomographic studies of rock properties, integrity of the cap rock and micro seismicity with time. These types of studies require expensive deployments of surface and borehole sensors in the vicinity of the CO2 injection wells. Another problem that may exist in CO2 sequestration fields is the potential for damaging induced seismicity associated with fluid injection into the geologic reservoir. Seismic hazard monitoring in CO2 sequestration fields requires a seismic network over a spatially larger region possibly having stations in remote settings. Expensive observatory-grade seismic systems are not necessary for seismic hazard deployments or small-scale tomographic studies. Hazard monitoring requires accurate location of induced seismicity to magnitude levels only slightly less than that which can be felt at the surface (e.g. magnitude 1), and the frequencies of interest for tomographic analysis are ~1 Hz and greater. We have developed a seismo/acoustic smart sensor system that can achieve the goals necessary for induced seismicity monitoring in CO2 sequestration fields. The unit is inexpensive, lightweight, easy to deploy, can operate remotely under harsh conditions and features 9 channels of recording (currently 3C 4.5 Hz geophone, MEMS accelerometer and microphone). An on-board processor allows for satellite transmission of parameter data to a processing center. Continuous or event-detected data is kept on two removable flash SD cards of up to 64+ Gbytes each. If available, data can be transmitted via cell phone modem or picked up via site visits. Low-power consumption allows for autonomous operation using only a 10 watt solar panel and a gel-cell battery. The system has been successfully tested for long-term (> 6 months) remote operations over a wide range

  5. Traffic forecasts ignoring induced demand

    DEFF Research Database (Denmark)

    Næss, Petter; Nicolaisen, Morten Skou; Strand, Arvid

    2012-01-01

    the model calculations included only a part of the induced traffic, the difference in cost-benefit results compared to the model excluding all induced traffic was substantial. The results show lower travel time savings, more adverse environmental impacts and a considerably lower benefitcost ratio when...... induced traffic is partly accounted for than when it is ignored. By exaggerating the economic benefits of road capacity increase and underestimating its negative effects, omission of induced traffic can result in over-allocation of public money on road construction and correspondingly less focus on other...... performance of a proposed road project in Copenhagen with and without short-term induced traffic included in the transport model. The available transport model was not able to include long-term induced traffic resulting from changes in land use and in the level of service of public transport. Even though...

  6. Paliperidone palmitate-induced sialorrhoea

    Directory of Open Access Journals (Sweden)

    Cengiz Cengisiz

    2016-03-01

    Full Text Available Extrapyramidal, metabolic, and cardiac side effects were reported for atypical antipsychotics; although a few resources show paliperidone-induced sialorrhea, there are no resources that show paliperidone palmitate-induced sialorrhea. In this paper, we present the paliperidone palmitate-induced sialorrhea side effects of a patient who applied on our clinic [Cukurova Med J 2016; 41(0.100: 8-13

  7. Radiation-induced cancer

    International Nuclear Information System (INIS)

    Dutrillaux, B.; CEA Fontenay-aux-Roses, 92

    1998-01-01

    The induction of malignant diseases is one of the most concerning late effects of ionising radiation. A large amount of information has been collected form atomic bomb survivors, patients after therapeutic irradiation, occupational follow-up and accidentally exposed populations. Major uncertainties persist in the (very) low range i.e, population and workers radioprotection. A review of the biological mechanisms leading to cancer strongly suggests that the vast majority of radiation-induced malignancies arise as a consequence of recessive mutations can be unveiled by ageing, this process being possibly furthered by constitutional or acquired genomic instability. The individual risk is likely to be very low, probably because of the usual dose level. However, the magnitude of medical exposure and the reliance of our societies on nuclear industry are so high that irreproachable decision-making processes and standards for practice are inescapable. (author)

  8. Radiation-induced nondisjunction

    International Nuclear Information System (INIS)

    Uchida, I.A.

    1979-01-01

    The methodology and results of epidemiological studies of the effects of preconception diagnostic x-rays of the abdomen on chromosome segregation in humans are described. The vast majority of studies show the same positive, though not significant, trend to increased nondisjunction among the offspring of irradiated women. The results of the various studies, however, cannot be pooled because of differing methodologies used. Abnormal chromosome segregation during mitotic division has been inducted experimentally by the in vitro exposure of human lymphocytes to a low dose of 50 R gamma irradiation. First meiotic nondisjunction has been successfully induced by whole body exposure of female mice to a low dose of radiation. The question of time-related repair of the mechanism involved in chromosome segregation is raised

  9. Radiation induced oral mucositis

    Directory of Open Access Journals (Sweden)

    P S Satheesh Kumar

    2009-01-01

    Full Text Available Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii who also received concomitant chemotherapy; (iii who received a total dose over 5,000 cGy; and (iv who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concerned. The present day management of oral mucositis is mostly palliative and or supportive care. The newer guidelines are suggesting Palifermin, which is the first active mucositis drug as well as Amifostine, for radiation protection and cryotherapy. The current management should focus more on palliative measures, such as pain management, nutritional support, and maintenance, of good oral hygiene

  10. Laser induced nuclear reactions

    International Nuclear Information System (INIS)

    Ledingham, Ken; McCanny, Tom; Graham, Paul; Fang Xiao; Singhal, Ravi; Magill, Joe; Creswell, Alan; Sanderson, David; Allott, Ric; Neely, David; Norreys, Peter; Santala, Marko; Zepf, Matthew; Watts, Ian; Clark, Eugene; Krushelnick, Karl; Tatarakis, Michael; Dangor, Bucker; Machecek, Antonin; Wark, Justin

    1998-01-01

    Dramatic improvements in laser technology since 1984 have revolutionised high power laser technology. Application of chirped-pulse amplification techniques has resulted in laser intensities in excess of 10 19 W/cm 2 . In the mid to late eighties, C. K. Rhodes and K. Boyer discussed the possibility of shining laser light of this intensity onto solid surfaces and to cause nuclear transitions. In particular, irradiation of a uranium target could induce electro- and photofission in the focal region of the laser. In this paper it is shown that μCi of 62 Cu can be generated via the (γ,n) reaction by a laser with an intensity of about 10 19 Wcm -2

  11. Radiation induced pesticidal microbes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ki Yup; Lee, Y. K.; Kim, J. S.; Kim, J. K.; Lee, S. J.; Lim, D. S

    2001-01-01

    To isolate pesticidal microbes against plant pathogenic fungi, 4 strains of bacteria(K1. K3, K4, YS1) were isolated from mushroom compost and hot spring. K4, K1, K3, YS1 strain showed wide antifungal spectrum and high antifungal activities against 12 kinds of fungi. Specific proteins and the specific transcribed genes were found from the YS1 and its radiation-induced mutants. And knock-out mutants of antifungal activity were derived by transposon mutagenesis. From these knock-out mutants, the antifungal activity related genes and its modification by gamma-ray radiation are going to be studied. These results suggested that radiation could be an useful tool for the induction of functional mutants.

  12. Radiation induced microbial pesticide

    International Nuclear Information System (INIS)

    Kim, Ki Yup; Lee, Young Keun; Kim, Jae Sung; Kim, Jin Kyu; Lee, Sang Jae

    2000-01-01

    To control plant pathogenic fungi, 4 strains of bacteria (K1, K3, K4, YS1) were isolated from mushroom compost and hot spring. K4, K1, K3, YS1 strain showed wide antifungal spectrum and high antifungal activities against 13 kinds of fungi. Mutants of K1 and YS1 strains were induced by gamma-ray radiation and showed promising antifungal activities. These wild type and mutants showed resistant against more than 27 kinds of commercial pesticides among 30 kinds of commercial pesticides test particularly, YS1-1006 mutant strain showed resistant against hydrogen oxide. And mutants had increased antifungal activity against Botryoshaeria dothidea. These results suggested that radiation could be an useful method for the induction of functional mutants. (author)

  13. Aripiprazole-induced priapism

    Directory of Open Access Journals (Sweden)

    Satya K Trivedi

    2016-01-01

    Full Text Available Priapism is a urologic emergency representing a true disorder of penile erection that persists beyond or is unrelated to sexual interest or stimulation. A variety of psychotropic drugs are known to produce priapism, albeit rarely, through their antagonistic action on alpha-1 adrenergic receptors. We report such a case of priapism induced by a single oral dose of 10 mg aripiprazole, a drug with the least affinity to adrenergic receptors among all atypical antipsychotics. Polymorphism of alpha-2A adrenergic receptor gene in schizophrenia patients is known to be associated with sialorrhea while on clozapine treatment. Probably, similar polymorphism of alpha-1 adrenergic receptor gene could contribute to its altered sensitivity and resultant priapism. In future, pharmacogenomics-based approach may help in personalizing the treatment and effectively prevent the emergence of such side effects.

  14. [Cannabis-induced disorders].

    Science.gov (United States)

    Soyka, M; Preuss, U; Hoch, E

    2017-03-01

    Use and misuse of cannabis and marihuana are frequent. About 5% of the adult population are current users but only 1.2% are dependent. The medical use of cannabis is controversial but there is some evidence for improvement of chronic pain and spasticity. The somatic toxicity of cannabis is well proven but limited and psychiatric disorders induced by cannabis are of more relevance, e.g. cognitive disorders, amotivational syndrome, psychoses and delusional disorders as well as physical and psychological dependence. The withdrawal symptoms are usually mild and do not require pharmacological interventions. To date there is no established pharmacotherapy for relapse prevention. Psychosocial interventions include psychoeducation, behavioral therapy and motivational enhancement. The CANDIS protocol is the best established German intervention among abstinence-oriented therapies.

  15. Induced seismicity. Final report

    International Nuclear Information System (INIS)

    Segall, P.

    1997-01-01

    The objective of this project has been to develop a fundamental understanding of seismicity associated with energy production. Earthquakes are known to be associated with oil, gas, and geothermal energy production. The intent is to develop physical models that predict when seismicity is likely to occur, and to determine to what extent these earthquakes can be used to infer conditions within energy reservoirs. Early work focused on earthquakes induced by oil and gas extraction. Just completed research has addressed earthquakes within geothermal fields, such as The Geysers in northern California, as well as the interactions of dilatancy, friction, and shear heating, on the generation of earthquakes. The former has involved modeling thermo- and poro-elastic effects of geothermal production and water injection. Global Positioning System (GPS) receivers are used to measure deformation associated with geothermal activity, and these measurements along with seismic data are used to test and constrain thermo-mechanical models

  16. Macroscopic Optomechanically Induced Transparency

    Science.gov (United States)

    Pate, Jacob; Castelli, Alessandro; Martinez, Luis; Thompson, Johnathon; Chiao, Ray; Sharping, Jay

    Optomechanically induced transparency (OMIT) is an effect wherein the spectrum of a cavity resonance is modified through interference between coupled excitation pathways. In this work we investigate a macroscopic, 3D microwave, superconducting radio frequency (SRF) cavity incorporating a niobium-coated, silicon-nitride membrane as the flexible boundary. The boundary supports acoustic vibrational resonances, which lead to coupling with the microwave resonances of the SRF cavity. The theoretical development and physical understanding of OMIT for our macroscopic SRF cavity is the same as that for other recently-reported OMIT systems despite vastly different optomechanical coupling factors and device sizes. Our mechanical oscillator has a coupling factor of g0 = 2 π . 1 ×10-5 Hz and is roughly 38 mm in diameter. The Q = 5 ×107 for the SRF cavity allows probing of optomechanical effects in the resolved sideband regime.

  17. [Glucocorticoid induced osteoporosis].

    Science.gov (United States)

    Anić, Branimir; Mayer, Miroslav

    2014-01-01

    Secondary osteoporosis most often develops due to glucocorticoid therapy. Glucocorticoids affect all stages of the bone remodeling cycle, its formation and resorption. Osteoblasts are primarily affected, decreasing their activity and enhancing apoptosis. Patients treated with glucocorticoids have lower bone mineral density and increased fracture risk. Glucocorticoid-induced osteoporosis can be prevented by administering the minimal effective dose of glucocorticoids, calcium and vitamin D supplementation or, if possible, by hormone replace- ment therapy. Moreover, appropriate physical activity should be encouraged. Patients who are at higher risk for low-energy fractures (for example post-menopausal women) have to be actively treated, usually with antiresorptive drugs among which bisphosphonates are currently the first line therapy.

  18. Radiation induced genomic instability

    International Nuclear Information System (INIS)

    Morgan, W.

    2003-01-01

    This presentation will focus on delayed genetic effects occurring in the progeny of cells after exposure to ionizing radiation. We have developed a model system for investigating those genetic effects occurring multiple generations after radiation exposure. The presentation will describe some of the delayed effects observed after radiation exposures including delayed chromosomal rearrangements, and recombination events as determined by a plasmid based assay system. We will present new data on how changes in gene expression as measured by differential display and DNA microarray analysis provides a mechanism by which cells display a memory of irradiation, and introduce candidate genes that may play a role in initiating and perpetuation the unstable phenotype. These results will be discussed in terms of the recently described non-targeted Death Inducing Effect (DIE) where by secreted factors from clones of unstable cells can elicit effects in non irradiated cells and may serve to perpetuate the unstable phenotype in cells that themselves were not irradiated

  19. Radiation induced pesticidal microbes

    International Nuclear Information System (INIS)

    Kim, Ki Yup; Lee, Y. K.; Kim, J. S.; Kim, J. K.; Lee, S. J.; Lim, D. S.

    2001-01-01

    To isolate pesticidal microbes against plant pathogenic fungi, 4 strains of bacteria(K1. K3, K4, YS1) were isolated from mushroom compost and hot spring. K4, K1, K3, YS1 strain showed wide antifungal spectrum and high antifungal activities against 12 kinds of fungi. Specific proteins and the specific transcribed genes were found from the YS1 and its radiation-induced mutants. And knock-out mutants of antifungal activity were derived by transposon mutagenesis. From these knock-out mutants, the antifungal activity related genes and its modification by gamma-ray radiation are going to be studied. These results suggested that radiation could be an useful tool for the induction of functional mutants

  20. Alcohol-Induced Blackout

    Directory of Open Access Journals (Sweden)

    Dai Jin Kim

    2009-11-01

    Full Text Available For a long time, alcohol was thought to exert a general depressant effect on the central nervous system (CNS. However, currently the consensus is that specific regions of the brain are selectively vulnerable to the acute effects of alcohol. An alcohol-induced blackout is the classic example; the subject is temporarily unable to form new long-term memories while relatively maintaining other skills such as talking or even driving. A recent study showed that alcohol can cause retrograde memory impairment, that is, blackouts due to retrieval impairments as well as those due to deficits in encoding. Alcoholic blackouts may be complete (en bloc or partial (fragmentary depending on severity of memory impairment. In fragmentary blackouts, cueing often aids recall. Memory impairment during acute intoxication involves dysfunction of episodic memory, a type of memory encoded with spatial and social context. Recent studies have shown that there are multiple memory systems supported by discrete brain regions, and the acute effects of alcohol on learning and memory may result from alteration of the hippocampus and related structures on a cellular level. A rapid increase in blood alcohol concentration (BAC is most consistently associated with the likelihood of a blackout. However, not all subjects experience blackouts, implying that genetic factors play a role in determining CNS vulnerability to the effects of alcohol. This factor may predispose an individual to alcoholism, as altered memory function during intoxication may affect an individual‟s alcohol expectancy; one may perceive positive aspects of intoxication while unintentionally ignoring the negative aspects. Extensive research on memory and learning as well as findings related to the acute effects of alcohol on the brain may elucidate the mechanisms and impact associated with the alcohol- induced blackout.

  1. Reassessment of area postrema's role in motion sickness and conditioned taste aversion

    Science.gov (United States)

    Daunton, Nancy G.; Brizzee, Kenneth R.; Corcoran, Meryl Lee; Crampton, G. H.; Damelio, F.; Elfar, S.; Fox, Robert A.

    1991-01-01

    On the basis of classical studies on the role of the area psotrema (AP) in motion-induced emesis it was generally accepted that the AP is an essential structure for the production of vomiting in response to motion. However, in more recent studies it has been demonstrated that vomiting induced by motion can still occur in animals in which the AP has been destroyed bilaterally. It was inferred from some of these more recent studies that the AP plays no role in motion-induced emesis. From the standpoint of the current understanding of central nervous system (CNS) plasticity, redundancy, remodeling, unmasking, regeneration, and recovery of function, however, it is important to realize the limitations of using ablation procedures to determine the functional role of a given neural structure in a highly integrated, adaptable central nervous system (CNS). For example, the results of our recent investigations in cat and squirrel monkey on the role of the AP in emesis and conditioned taste aversion induced by motion indicate that while AP lesions do not prevent motion-induced emesis when animals are tested 30 days or more after surgery, the lesions do change the latency to emesis. Thus, contradictory findings from lesion studies must be evaluated not only in terms of species difference, differences in lesioning techniques and extent of lesions, and in stimulus parameters, but also in terms of duration of the recovery period, during which significant recovery of function may take place. In our judgment, inadequate consideration of the foregoing factors could lead to erroneous inferences about given structure's role in the behavior of the intact, nonablated animal.

  2. Radiation induced nano structures

    International Nuclear Information System (INIS)

    Ibragimova, E.M.; Kalanov, M.U.; Khakimov, Z.

    2006-01-01

    Full text: Nanometer-size silicon clusters have been attracting much attention due to their technological importance, in particular, as promising building blocks for nano electronic and nano photonic systems. Particularly, silicon wires are of great of interest since they have potential for use in one-dimensional quantum wire high-speed field effect transistors and light-emitting devices with extremely low power consumption. Carbon and metal nano structures are studied very intensely due to wide possible applications. Radiation material sciences have been dealing with sub-micron objects for a long time. Under interaction of high energy particles and ionizing radiation with solids by elastic and inelastic mechanisms, at first point defects are created, then they form clusters, column defects, disordered regions (amorphous colloids) and finally precipitates of another crystal phase in the matrix. Such irradiation induced evolution of structure defects and phase transformations was observed by X-diffraction techniques in dielectric crystals of quartz and corundum, which exist in and crystal modifications. If there is no polymorphism, like in alkali halide crystals, then due to radiolysis halogen atoms are evaporated from the surface that results in non-stoichiometry or accumulated in the pores formed by metal vacancies in the sub-surface layer. Nano-pores are created by intensive high energy particles irradiation at first chaotically and then they are ordered and in part filled by inert gas. It is well-known mechanism of radiation induced swelling and embrittlement of metals and alloys, which is undesirable for construction materials for nuclear reactors. Possible solution of this problem may come from nano-structured materials, where there is neither swelling nor embrittlement at gas absorption due to very low density of the structure, while strength keeps high. This review considers experimental observations of radiation induced nano-inclusions in insulating

  3. Prolactin induces adrenal hypertrophy

    Directory of Open Access Journals (Sweden)

    E.J. Silva

    2004-02-01

    Full Text Available Although adrenocorticotropic hormone is generally considered to play a major role in the regulation of adrenal glucocorticoid secretion, several reports have suggested that other pituitary hormones (e.g., prolactin also play a significant role in the regulation of adrenal function. The aim of the present study was to measure the adrenocortical cell area and to determine the effects of the transition from the prepubertal to the postpubertal period on the hyperprolactinemic state induced by domperidone (4.0 mg kg-1 day-1, sc. In hyperprolactinemic adult and young rats, the adrenals were heavier, as determined at necropsy, than in the respective controls: adults (30 days: 0.16 ± 0.008 and 0.11 ± 0.007; 46 days: 0.17 ± 0.006 and 0.12 ± 0.008, and 61 days: 0.17 ± 0.008 and 0.10 ± 0.004 mg for treated and control animals, respectively; P < 0.05, and young rats (30 days: 0.19 ± 0.003 and 0.16 ± 0.007, and 60 days: 0.16 ± 0.006 and 0.13 ± 0.009 mg; P < 0.05. We selected randomly a circular area in which we counted the nuclei of adrenocortical cells. The area of zona fasciculata cells was increased in hyperprolactinemic adult and young rats compared to controls: adults: (61 days: 524.90 ± 47.85 and 244.84 ± 9.03 µm² for treated and control animals, respectively; P < 0.05, and young rats: (15 days: 462.30 ± 16.24 and 414.28 ± 18.19; 60 days: 640.51 ± 12.91 and 480.24 ± 22.79 µm²; P < 0.05. Based on these data we conclude that the increase in adrenal weight observed in the hyperprolactinemic animals may be due to prolactin-induced adrenocortical cell hypertrophy.

  4. Congruence properties of induced representations

    DEFF Research Database (Denmark)

    Mayer, Dieter; Momeni, Arash; Venkov, Alexei

    In this paper we study representations of the projective modular group induced from the Hecke congruence group of level 4 with Selberg's character. We show that the well known congruence properties of Selberg's character are equivalent to the congruence properties of the induced representations...

  5. Laser-induced nuclear fusion

    International Nuclear Information System (INIS)

    Jablon, Claude

    1977-01-01

    Research programs on laser-induced thermonuclear fusion in the United States, in Europe and in USSR are reviewed. The principle of the fusion reactions induced is explained, together with the theoretical effects of the following phenomena: power and type of laser beams, shape and size of the solid target, shock waves, and laser-hydrodynamics coupling problems [fr

  6. Force induced DNA melting

    International Nuclear Information System (INIS)

    Santosh, Mogurampelly; Maiti, Prabal K

    2009-01-01

    When pulled along the axis, double-strand DNA undergoes a large conformational change and elongates by roughly twice its initial contour length at a pulling force of about 70 pN. The transition to this highly overstretched form of DNA is very cooperative. Applying a force perpendicular to the DNA axis (unzipping), double-strand DNA can also be separated into two single-stranded DNA, this being a fundamental process in DNA replication. We study the DNA overstretching and unzipping transition using fully atomistic molecular dynamics (MD) simulations and argue that the conformational changes of double-strand DNA associated with either of the above mentioned processes can be viewed as force induced DNA melting. As the force at one end of the DNA is increased the DNA starts melting abruptly/smoothly above a critical force depending on the pulling direction. The critical force f m , at which DNA melts completely decreases as the temperature of the system is increased. The melting force in the case of unzipping is smaller compared to the melting force when the DNA is pulled along the helical axis. In the case of melting through unzipping, the double-strand separation has jumps which correspond to the different energy minima arising due to sequence of different base pairs. The fraction of Watson-Crick base pair hydrogen bond breaking as a function of force does not show smooth and continuous behavior and consists of plateaus followed by sharp jumps.

  7. Chemotherapy-induced hypocalcemia.

    Science.gov (United States)

    Ajero, Pia Marie E; Belsky, Joseph L; Prawius, Herbert D; Rella, Vincent

    2010-01-01

    To present a unique case of transient, asymptomatic chemotherapy-induced hypocalcemia not attributable to hypomagnesemia or tumor lysis syndrome and review causes of hypocalcemia related to cancer with and without use of chemotherapy. We present a case detailing the clinical and laboratory findings of a patient who had severe hypocalcemia during chemotherapy and discuss causes of hypocalcemia with an extensive literature review of chemotherapeutic agents associated with this biochemical abnormality. In a 90-year-old man, hypocalcemia developed during 2 courses of chemotherapy for Hodgkin lymphoma, with partial recovery between courses and normal serum calcium 10 months after completion of treatment. Magnesium, vitamin D, and parathyroid hormone levels were low normal. There was no evidence of tumor lysis syndrome. Of the various agents administered, vinca alkaloids seemed the most likely cause. Serial testing suggested that the underlying mechanism may have been acquired, reversible hypoparathyroidism. No other similar case was found in the published literature. The severe hypocalcemia in our patient could not be attributed to hypomagnesemia or tumor lysis syndrome, and it was clearly associated with the timing of his chemotherapeutic regimen. Possibilities include direct parathyroid hormone suppression or alteration of calcium sensing by the chemotherapeutic drugs. Serum calcium surveillance before and during chemotherapeutic management of cancer patients may reveal more instances and provide insight into the exact mechanism of this lesser known yet striking complication.

  8. Collision-induced coherence

    International Nuclear Information System (INIS)

    Bloembergen, N.

    1985-01-01

    Collision-induced coherence is based on the elimination of phase correlations between coherent Feynman-type pathways which happen to interfere destructively in the absence of damping for certain nonlinear processes. One consequence is the appearance of the extra resonances in four-wave light mixing experiments, for which the intensity increases with increasing buffer gas pressure. These resonances may occur between a pair of initially unpopulated excited states, or between a pair of initially equally populated ground states. The pair of levels may be Zeeman substrates which became degenerate in zero magnetic field. The resulting collision-enhanced Hanle resonances can lead to very sharp variations in the four-wave light mixing signal as the external magnetic field passes through zero. The theoretical description in terms of a coherence grating between Zeeman substrates is equivalent to a description in terms of a spin polarization grating obtained by collision-enhanced transverse optical pumping. The axis of quantization in the former case is taken perpendicular to the direction of the light beams; in the latter case is taken parallel to this direction

  9. Linezolid induced retinopathy.

    Science.gov (United States)

    Park, Dae Hyun; Park, Tae Kwann; Ohn, Young-Hoon; Park, Jong Sook; Chang, Jee Ho

    2015-12-01

    While optic neuropathy is a well-known cause of visual disturbances in linezolid-treated patients, the possibility of linezolid-related retinopathy has not been investigated. Here, we report a case of retinopathy demonstrated by multifocal electroretinogram (mfERG) in a linezolid-treated patient. A 61-year-old man with extensively drug-resistant pulmonary tuberculosis treated with linezolid for 5 months presented with painless loss of vision in both eyes. The patient's best corrected visual acuity was 20/50 in the right eye and 20/100 in the left eye. Fundus examination revealed mild disc edema, and color vision was defective in both eyes. Humphrey visual field tests showed a superotemporal field defect in the right eye and central and pericentral field defect in the left eye. Optical coherence tomography (OCT) revealed only mild optic disc swelling. In mfERG, central amplitudes were depressed in both eyes. Four months after the cessation of linezolid, visual acuity was restored to 20/20 right eye and 20/25 left eye. The color vision and visual field had improved. The OCT and mfEFG findings improved as well. Although the clinical features were similar to linezolid-induced optic neuropathy, the mfERG findings suggest the possibility of a retinopathy through cone dysfunction.

  10. Food-induced anaphylaxis.

    Science.gov (United States)

    Järvinen, Kirsi M

    2011-06-01

    Food-induced anaphylaxis is the leading single cause of anaphylaxis treated in emergency departments and increasing in prevalence. Food allergy is an increasing problem in westernized countries around the world, with a cumulative prevalence of 3-6%. Peanut, tree nuts, and shellfish are the most commonly implicated foods in anaphylaxis, although milk is a common trigger in children. Asthmatics, adolescents, and those with a prior reaction are at increased risk for more severe reactions. Most first reactions and reactions in children most commonly occur at home, whereas most subsequent reactions and reactions in adults occur outside home. Studies on schools have identified inadequate management plans and symptom recognition whereas those on restaurants report lack of prior notification by allergic individuals and lack in staff education. Epinephrine, although underutilized is the drug of choice with multiple doses needed in up to one-fifth of reactions. Diagnosis is currently based on convincing history and allergy testing supported by elevated serum tryptase, if available. Long-term management includes strict avoidance and emergency action plan. With a growing population of food-allergic children and adults, markers to predict which individuals are at increased risk for anaphylaxis as well as new therapies are vigorously sought.

  11. Methaemoglobinemia Induced by MDMA?

    Directory of Open Access Journals (Sweden)

    L. L. W. Verhaert

    2011-01-01

    Full Text Available Case. A 45-year-old man with a blank medical history presented at the emergency room with dizziness and cyanosis. Physical examination showed cyanosis with a peripheral saturation (SpO2 of 85%, he did not respond to supplemental oxygen. Arterial blood gas analysis showed a striking chocolate brown colour. Based on these data, we determined the arterial methaemoglobin concentration. This was 32%. We gave 100% oxygen and observed the patient in a medium care unit. The next day, patient could be discharged in good condition. Further inquiry about exhibitions and extensive history revealed that the patient used MDMA (3,4- methylenedioxymethamphetamine, the active ingredient of ecstasy. Conclusion. Acquired methaemoglobinemia is a condition that occurs infrequently, but is potentially life threatening. Different nutrients, medications, and chemicals can induce methaemoglobinemia by oxidation of haemoglobin. The clinical presentation of a patient with methaemoglobinemia is due to the impossibility of O2 binding and transport, resulting in tissue hypoxia. Important is to think about methaemoglobin in a patient who presents with cyanosis, a peripheral saturation of 85% that fails to respond properly to the administration of O2. Because methaemoglobin can be reduced physiologically, it is usually sufficient to remove the causative agent, to give O2, and to observe the patient.

  12. Induced mutations in castor

    International Nuclear Information System (INIS)

    Ganesan, K.; Javad Hussain, H.S.; Vindhiyavarman, P.

    2001-01-01

    Castor (Ricinus communis L.) is an important oilseed crop in India. To create variability mutations were induced in two cultivars 'TMV5' (maturing in 130-140 days) and 'CO1' (perennial type). Gamma rays and diethyl sulphate and ethidium bromide were used for seed treatment. Ten doses, from 100 to 1000 Gy were employed. For chemical mutagenesis five concentrations of mutagenes from 10 to 50 mM were tried. No economic mutants could be isolated after treatment with the chemical mutagens. The following economic mutants were identified in the dose 300 Gy of gamma rays. Annual types from perennial CO 1 castor CO 1 is a perennial variety (8-10 years) with bold seeds (100 seed weight 90 g) and high oil content (57%). Twenty-one lines were isolated with annual types (160-180 days) with high yield potential as well as bold seeds and high oil content. These mutants, identified in M 3 generation were bred true in subsequent generations up to M 8 generation. Critical evaluation of the mutants in yield evaluation trials is in progress

  13. Laughter-induced syncope.

    Science.gov (United States)

    Kim, Alexander J; Frishman, William H

    2012-01-01

    Reported cases of syncope caused directly by laughter are rare. The common scenario described in a few reports involved episodes of fortuitous laughter, sometimes followed by a short prodrome of lightheadedness, facial flushing, and dizziness, followed by an episode of definite syncope. There were no seizure-like movements, automatisms, or bladder or bowel incontinence. After the syncopal episodes that were seconds in length, the patients regained consciousness, and at that point were fully oriented. These episodes could recur in a similar situation with such laughter. Many of these patients subsequently underwent full syncope workups, without elucidating a primary cardiac or neurologic cause. In this review of laughter-induced syncope, we describe a patient of ours who fit these descriptions. This phenomenon is likely a subtype of benign Valsalva-related syncope, with autonomic reflex arcs coming into play that ultimately result in global cerebral hypoperfusion. Besides the Valsalva produced by a great fit of laughter, laughter itself has its own neuroendocrine and vasculature effects that may play a role.

  14. Radiation-induced cerebrovasculopathy

    International Nuclear Information System (INIS)

    Ikeyama, Yukihide; Abiko, Seisho; Kurokawa, Yasushi; Okamura, Tomomi; Watanabe, Kohsaku; Inoue, Shinichi; Fujii, Yasuhiro.

    1993-01-01

    We reported a patient who suffered from cerebrovasculopathy after irradiation therapy for astrocytoma located at the left temporal lobe. An eleven year-old boy who presented with headache and vomiting received partial removal of a tumor. Histological diagnosis of the tumor was astrocytoma (grade II). His preoperative cerebral angiograms showed mass sign solely, without stenosis or occlusion of the cerebral vessel. Postoperatively, he was treated with irradiation therapy involving the whole brain with a total of 30 Gy, and gamma knife therapy. Six months after irradiation, he started suffering from frequent cerebral ischemic attacks, but there was no regrowth of the tumor visible on CT scans. Cerebral angiograms were made again, and revealed multifocal stenoses in the bilateral internal carotid arteries, middle cerebral arteries, and the anterior cerebral artery. His symptoms did not improve after conservative treatment with steroids, calcium antagonist, or low molecular weight dextran. Although he received a superficial temporal artery-middle cerebral artery (STA-MCA) anastomoses bilaterally, multiple cerebral infarctions appeared. Although irradiation therapy is acceptable in patients with brain tumor, cerebrovasculopathy after irradiation should be considered as one of the most important complications, and the risk incurred by irradiation therapy should lead to more careful consideration and caution when treating intracranial brain tumors, especially in children. From our experience, the usefulness of bypass surgery for radiation-induced cerebrovasculopathy is still controversial. (author)

  15. Temozolomide-Induced Myelodysplasia

    Directory of Open Access Journals (Sweden)

    Ethan A. Natelson

    2010-01-01

    Full Text Available A patient who had received temozolomide (TMZ as a single agent in treatment of malignant glioma developed therapy-induced myelodysplasia (T-MDS. TMZ is an orally active imidazotetrazine which methylates guanine residues in DNA, ultimately causing single and double-strand DNA breaks leading to apoptotic cell death. TMZ does not chemically cross-link DNA and is considered a nonclassical alkylating agent, similar in structure and activity to dacarbazine. Observations on this patient, and on similarly treated others, suggest that the cumulative dose threshold (CDT for TMZ that predisposes to T-MDS and which may potentially lead to acute myeloid leukemia (T-AML is around 18000 to 20000 mg/sq m. Although the incidence of T-MDS and the predisposing CDT of TMZ may differ from that of other potentially leukemogenic compounds currently and formerly used as chemotherapeutic agents, all alkylating agents, including TMZ, should be considered potentially leukemogenic when administered long term.

  16. Microbiologically induced corrosion

    International Nuclear Information System (INIS)

    Stein, A.A.

    1988-01-01

    Biological attack is a problem that can affect all metallic materials in a variety of environments and systems. In the power industry, corrosion studies have focused on condensers and service water systems where slime, barnacles, clams, and other macro-organisms are easily detected. Efforts have been made to eliminate the effect of these organisms through the use of chlorination, backflushing, organic coating, or thermal shock. The objective is to maintain component performance by eliminating biofouling and reducing metallic corrosion. Recently, corrosion of power plant components by micro-organisms (bacteria) has been identified even in very clean systems. A system's first exposure to microbiologically induced corrosion (MIC) occurs during its first exposure to an aqueous environment, such as during hydrotest or wet layup. Corrosion of buried pipelines by sulfate-reducing bacteria has been studied by the petrochemical industry for years. This paper discusses various methods of diagnosing, monitoring, and controlling MIC in a variety of systems, as well as indicates areas where further study is needed

  17. Doxycycline induced Esophagitis

    Directory of Open Access Journals (Sweden)

    Banu Karakus Yilmaz

    2014-02-01

    Full Text Available Esophagitis is a hazardous condition such as acid reflux of esophageal mucosa, infection, systemic diseases, radiation, drugs and trauma. Drug- induced esophagial injury (DIEI is a disease with the use of variety of drugs that caused serious damage and ulcer in the mucosa of the esophagus. The most commonly implicated drugs are non-steroidal anti-inflammatory drugs (NSAIDs, chloride and especially antibiotics. Thirty-six year-old female patient presented to the emergency department with odynophagia during swallowing and complaining of retrosternal pain. One week before 100 mg doxycycline (2x1 PO for therapeutic abortion were prescribed. It was learned that in the third day of the initiation of medication, the patient\\'s symptoms began and stopped using drug by the fourth day due to advers effect of drugs, but her symptoms didn’t regressed although she didn’t use them. Endoscopy appointment was taken, proton pump inhibitor and antiacid treatment was given, than patient was discharged from the emergency department. In the endoscopy, 20 mm segment esophageal ulcer was seen approximately in the 30.th cm of the esophagius. DIEI is a relatively common, although under-recognized, so this case was presented for remainding DIEI to emergency medicine personals and reweiving its diagnosis, treatment and follow-up.

  18. Ceftazidime-induced thrombocytopenia.

    Science.gov (United States)

    Domingo-Chiva, E; Díaz-Rangel, M; Monsalve-Naharro, J Á; Cuesta-Montero, P; Catalá-Ripoll, J V; García-Martínez, E M

    2017-12-01

    Ceftazidime is an antibiotic belonging to the group of third generation cephalosporins, frequently used in clinical practice for its broad antibacterial spectrum. A case report is presented on a 78-year-old man who entered the intensive care unit due to respiratory failure secondary to nosocomial pneumonia in the postoperative period of a laparoscopic hepatic bisegmentectomy for a hepatocarcinoma. It required invasive mechanical ventilation and was treated with ceftazidime, developing a progressive decrease in platelet count after the onset of this drug and after re-exposure to it, not coinciding with the introduction of other drugs. The adverse reaction was reported to the Spanish pharmacosurveillance system and according to the Naranjo algorithm the causal relationship was probable. Since no case of ceftazidime-induced thrombocytopenia was found in the literature, we consider knowledge of it relevant as an adverse effect to be taken into account given its potential severity, especially when it cannot be explained by other causes. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Neutron induced electron radiography

    International Nuclear Information System (INIS)

    Andrade, Marcos Leandro Garcia

    2008-01-01

    In the present paper a new radiography technique, the 'Neutron Induced Electron Radiography' - NIER, to inspect low thickness samples on the order of micra, has been developed. This technique makes use of low energy electrons as penetrating radiation generated from metallic gadolinium screens when irradiated by thermal neutrons. The conditions to obtain the best image for the conventional X-ray film Kodak-AA were determined by using a digital system to quantify the darkening level of the film. The irradiations have been performed at a radiography equipment installed at the beam-hole no. 8 of the 5 MW IEA-R1 nuclear research reactor of IPEN-CNEN/SP. The irradiation time to obtain the best radiography was 100 seconds and for such condition the technique was able to discern 1 μm in 24 μm of aluminum at a resolution of 32 μm. By visual comparison the images obtained by the NIER shown a higher quality when compared with the ones from other usual techniques the make use of electrons a penetrating radiation and films for image registration. Furthermore the use of the digital system has provided a smaller time for data acquisition and data analysis as well as an improvement in the image visualization. (author)

  20. Ion-induced sputtering

    International Nuclear Information System (INIS)

    Yamamura, Yasumichi; Shimizu, Ryuichi; Shimizu, Hazime; Ito, Noriaki.

    1983-01-01

    The research on ion-induced sputtering has been continued for a long time, since a hundred or more years ago. However, it was only in 1969 by Sigmund that the sputtering phenomena were theoretically arranged into the present form. The reason why the importance of sputtering phenomena have been given a new look recently is the application over wide range. This paper is a review centering around the mechanism of causing sputtering and its characteristics. Sputtering is such a phenomenon that the atoms in the vicinity of a solid surface are emitted into vacuum by receiving a part of ion energy, or in other words, it is a kind of irradiation damage in the vicinity of a solid surface. In this meaning, it can be considered that the sputtering based on the ions located on the clean surface of a single element metal is simple, and has already been basically understood. On the contrary, the phenomena can not be considered to be fully understood in the case of alloys and compounds, because these surface conditions under irradiation are not always clear due to segregation and others. In the paper, the physical of sputtering, single element sputtering, the sputtering in alloys and compounds, and the behaviour of emitted particles are explained. Finally, some recent topics of the sputtering measurement by laser resonant excitation, the sputtering by electron excitation, chemical sputtering, and the sputtering in nuclear fusion reactors are described. (Wakatsuki, Y.)

  1. Tumor-induced osteomalacia

    Science.gov (United States)

    Chong, William H; Molinolo, Alfredo A; Chen, Clara C; Collins, Michael T

    2012-01-01

    Tumor-induced osteomalacia (TIO) is a rare and fascinating paraneoplastic syndrome in which patients present with bone pain, fractures, and muscle weakness. The cause is high blood levels of the recently identified phosphate and vitamin D-regulating hormone, fibroblast growth factor 23 (FGF23). In TIO, FGF23 is secreted by mesenchymal tumors that are usually benign, but are typically very small and difficult to locate. FGF23 acts primarily at the renal tubule and impairs phosphate reabsorption and 1α-hydroxylation of 25-hydroxyvitamin D, leading to hypophosphatemia and low levels of 1,25-dihydroxy vitamin D. A step-wise approach utilizing functional imaging (F-18 fluorodeoxyglucose positron emission tomography and octreotide scintigraphy) followed by anatomical imaging (computed tomography and/or magnetic resonance imaging), and, if needed, selective venous sampling with measurement of FGF23 is usually successful in locating the tumors. For tumors that cannot be located, medical treatment with phosphate supplements and active vitamin D (calcitriol or alphacalcidiol) is usually successful; however, the medical regimen can be cumbersome and associated with complications. This review summarizes the current understanding of the pathophysiology of the disease and provides guidance in evaluating and treating these patients. Novel imaging modalities and medical treatments, which hold promise for the future, are also reviewed. PMID:21490240

  2. Laxative-induced rhabdomyolysis

    Directory of Open Access Journals (Sweden)

    Alfonso Merante

    2010-03-01

    Full Text Available Alfonso Merante1, Pietro Gareri2,3, Norma Maria Marigliano2, Salvatore De Fazio2, Elvira Bonacci1, Carlo Torchia1, Gaetano Russo1, Pasquale Lacroce1, Roberto Lacava3, Alberto Castagna3, Giovambattista De Sarro2, Giovanni Ruotolo11Geriatrist, Geriatric Unit “Pugliese-Ciaccio” Hospital, Catanzaro, Italy; 2Department of Experimental and Clinical Medicine, Faculty of Medicine and Surgery, University Magna Graecia of Catanzaro, Clinical Pharmacology and Pharmacovigilance Unit, Mater Domini University Hospital, Catanzaro, Italy; 3Geriatrist, Operative Unit Elderly Health Care, Catanzaro, ItalyAbstract: The present study describes a case of laxative-induced rhabdomyolysis in an elderly patient. An 87-year-old woman was hospitalized for the onset of confusion, tremors, an inability to walk, and a fever that she had been experiencing for 36 hours. She often took high dosages of lactulose and sorbitol syrup as a laxative (about 70 g/day. During her physical examination, the patient was confused, drowsy, and she presented hyposthenia in her upper and lower limbs, symmetric and diffuse moderate hyporeflexia, and her temperature was 37.8°C. Laboratory tests revealed severe hyponatremia with hypokalemia, hypocalcemia, hypochloremia, and metabolic alkalosis. Moreover, rhabdomyolysis markers were found. The correction of hydroelectrolytic imbalances with saline, potassium and sodium chlorure, calcium gluconate was the first treatment. During her hospitalization the patient presented acute delirium, treated with haloperidol and prometazine chloridrate intramuscularly. She was discharged 12 days later, after resolution of symptoms, and normalized laboratory tests. Over-the-counter drugs such as laxatives are usually not considered dangerous; on the other hand, they may cause serum electrolytic imbalance and rhabdomyolysis. A careful monitoring of all the drugs taken by the elderly is one of the most important duties of a physician since drug interactions and

  3. Tumour-induced osteomalacia.

    Science.gov (United States)

    Minisola, Salvatore; Peacock, Munro; Fukumoto, Seijii; Cipriani, Cristiana; Pepe, Jessica; Tella, Sri Harsha; Collins, Michael T

    2017-07-13

    Tumour-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a rare paraneoplastic disorder caused by tumours that secrete fibroblast growth factor 23 (FGF23). Owing to the role of FGF23 in renal phosphate handling and vitamin D synthesis, TIO is characterized by decreased renal tubular reabsorption of phosphate, by hypophosphataemia and by low levels of active vitamin D. Chronic hypophosphataemia ultimately results in osteomalacia (that is, inadequate bone mineralization). The diagnosis of TIO is usually suspected when serum phosphate levels are chronically low in the setting of bone pain, fragility fractures and muscle weakness. Locating the offending tumour can be very difficult, as the tumour is often very small and can be anywhere in the body. Surgical removal of the tumour is the only definitive treatment. When the tumour cannot be located or when complete resection is not possible, medical treatment with phosphate salts or active vitamin D is necessary. One of the most promising emerging treatments for unresectable tumours that cause TIO is the anti-FGF23 monoclonal antibody KRN23. The recent identification of a fusion of fibronectin and fibroblast growth factor receptor 1 (FGFR1) as a molecular driver in some tumours not only sheds light on the pathophysiology of TIO but also opens the door to a better understanding of the transcription, translocation, post-translational modification and secretion of FGF23, as well as suggesting approaches to targeted therapy. Further study will reveal if the FGFR1 pathway is also involved in tumours that do not harbour the translocation.

  4. Eicosanoids and Respiratory Viral Infection: Coordinators of Inflammation and Potential Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    Mary K. McCarthy

    2012-01-01

    Full Text Available Viruses are frequent causes of respiratory infection, and viral respiratory infections are significant causes of hospitalization, morbidity, and sometimes mortality in a variety of patient populations. Lung inflammation induced by infection with common respiratory pathogens such as influenza and respiratory syncytial virus is accompanied by increased lung production of prostaglandins and leukotrienes, lipid mediators with a wide range of effects on host immune function. Deficiency or pharmacologic inhibition of prostaglandin and leukotriene production often results in a dampened inflammatory response to acute infection with a respiratory virus. These mediators may, therefore, serve as appealing therapeutic targets for disease caused by respiratory viral infection.

  5. Catecholamine induced cardiomyopathy in pheochromocytoma

    Directory of Open Access Journals (Sweden)

    Ron Thomas Varghese

    2013-01-01

    Full Text Available Catecholamine induced cardiomyopathy in the setting of pheochromocytoma is an unusual clinical entity. Earlier studies have reported left ventricular dysfunction in around 10% of subjects with pheochromocytoma. [1] Catecholamine induced vasoconstriction, direct toxic effect of byproducts of catecholamine degradation and direct receptor-mediated mechanisms are thought to contribute to cardiomyopathy in subjects with pheochromocytoma. The presentation remains a diagnostic challenge as patients may already have hypertensive heart disease and acute coronary syndrome on account of uncontrolled secondary hypertension. We report a case of a 42-year-old male, who presented with features of pheochromocytoma induced cardiomyopathy.

  6. Cisplatin-Induced Eosinophilic Pneumonia

    Directory of Open Access Journals (Sweden)

    Hideharu Ideguchi

    2014-01-01

    Full Text Available A 67-year-old man suffering from esophageal cancer was admitted to our hospital complaining of dyspnea and hypoxemia. He had been treated with cisplatin, docetaxel, and fluorouracil combined with radiotherapy. Chest computed tomography revealed bilateral ground-glass opacity, and bronchoalveolar lavage fluid showed increased eosinophils. Two episodes of transient eosinophilia in peripheral blood were observed after serial administration of anticancer drugs before the admission, and drug-induced lymphocyte stimulation test to cisplatin was positive. Thus cisplatin-induced eosinophilic pneumonia was suspected, and corticosteroid was effectively administered. To our knowledge, this is the first reported case of cisplatin-induced eosinophilic pneumonia.

  7. Systemic resistance induced by rhizosphere bacteria

    NARCIS (Netherlands)

    Loon, L.C. van; Bakker, P.A.H.M.; Pieterse, C.M.J.

    1998-01-01

    Nonpathogenic rhizobacteria can induce a systemic resistance in plants that is phenotypically similar to pathogen-induced systemic acquired resistance (SAR). Rhizobacteria-mediated induced systemic resistance (ISR) has been demonstrated against fungi, bacteria, and viruses in Arabidopsis, bean,

  8. Tumor-induced osteomalacia

    Directory of Open Access Journals (Sweden)

    Pablo Florenzano

    2017-12-01

    Full Text Available Tumor-induced osteomalacia (TIO is a rare paraneoplastic syndrome clinically characterized by bone pain, fractures and muscle weakness. It is caused by tumoral overproduction of fibroblast growth factor 23 (FGF23 that acts primarily at the proximal renal tubule, decreasing phosphate reabsorption and 1α-hydroxylation of 25 hydroxyvitamin D, thus producing hypophosphatemia and osteomalacia. Lesions are typically small, benign mesenchymal tumors that may be found in bone or soft tissue, anywhere in the body. In up to 60% of these tumors, a fibronectin-1(FN1 and fibroblast growth factor receptor-1 (FGFR1 fusion gene has been identified that may serve as a tumoral driver. The diagnosis is established by the finding of acquired chronic hypophosphatemia due to isolated renal phosphate wasting with concomitant elevated or inappropriately normal blood levels of FGF23 and decreased or inappropriately normal 1,25-OH2-Vitamin D (1,25(OH2D. Locating the tumor is critical, as complete removal is curative. For this purpose, a step-wise approach is recommended, starting with a thorough medical history and physical examination, followed by functional imaging. Suspicious lesions should be confirmed by anatomical imaging, and if needed, selective venous sampling with measurement of FGF23. If the tumor is not localized, or surgical resection is not possible, medical therapy with phosphate and active vitamin D is usually successful in healing the osteomalacia and reducing symptoms. However, compliance is often poor due to the frequent dosing regimen and side effects. Furthermore, careful monitoring is needed to avoid complications such us secondary/tertiary hyperparathyroidism, hypercalciuria, and nephrocalcinosis. Novel therapeutical approaches are being developed for TIO patients, such as image-guided tumor ablation and medical treatment with the anti-FGF23 monoclonal antibody KRN23 or anti FGFR medications. The case of a patient with TIO is presented to

  9. Infrasonic induced ground motions

    Science.gov (United States)

    Lin, Ting-Li

    On January 28, 2004, the CERI seismic network recorded seismic signals generated by an unknown source. Our conclusion is that the acoustic waves were initiated by an explosive source near the ground surface. The meteorological temperature and effective sound speed profiles suggested existence of an efficient near-surface waveguide that allowed the acoustic disturbance to propagate to large distances. An explosion occurring in an area of forest and farms would have limited the number of eyewitnesses. Resolution of the source might be possible by experiment or by detailed analysis of the ground motion data. A seismo-acoustic array was built to investigate thunder-induced ground motions. Two thunder events with similar N-wave waveforms but different horizontal slownesses are chosen to evaluate the credibility of using thunder as a seismic source. These impulsive acoustic waves excited P and S reverberations in the near surface that depend on both the incident wave horizontal slowness and the velocity structure in the upper 30 meters. Nineteen thunder events were chosen to further investigate the seismo-acoustic coupling. The consistent incident slowness differences between acoustic pressure and ground motions suggest that ground reverberations were first initiated somewhat away from the array. Acoustic and seismic signals were used to generate the time-domain transfer function through the deconvolution technique. Possible non-linear interaction for acoustic propagation into the soil at the surface was observed. The reverse radial initial motions suggest a low Poisson's ratio for the near-surface layer. The acoustic-to-seismic transfer functions show a consistent reverberation series of the Rayleigh wave type, which has a systematic dispersion relation to incident slownesses inferred from the seismic ground velocity. Air-coupled Rayleigh wave dispersion was used to quantitatively constrain the near-surface site structure with constraints afforded by near-surface body

  10. [Medical induced abortion].

    Science.gov (United States)

    Bettahar, K; Pinton, A; Boisramé, T; Cavillon, V; Wylomanski, S; Nisand, I; Hassoun, D

    2016-12-01

    Updated clinical recommendations for medical induced abortion procedure. A systematic review of French and English literature, reviewing the evidence relating to the provision of medical induced abortion was carried out on PubMed, Cochrane Library and international scientific societies recommendations. The effectiveness of medical abortion is higher than 95% when the protocols are adjusted to gestational age (EL1). Misoprostol alone is less effective than a combination of mifepristone and misoprostol (EL1). Gemeprost is less effective than misoprostol (EL2). The dose of 200mg of mifepristone should be preferred to 600mg (NP1, Rank A). Mifepristone can be taken at home (professional agreement). The optimum interval between mifepristone and misoprostol intake should be 24 to 48 hours (EL1, grade A). Before 7 weeks LMP, the dose of 400μg misoprostol should be given orally (EL1, grade A) eventually repeated after 3hours if no bleeding occurs. For optimal effectiveness between 7 and 14 LMP, the interval between mifepristone and misoprostol should not be shortened to less than 8hours (grade 1). An interval of 24 to 48hours will not affect the effectiveness of the method provided misoprostol dosage is 800μg (EL1). Vaginal, sublingual or buccal routes of administration are more effective and better tolerated than the oral route, which should be abandoned (EL1). An amount of 800μg sublingual or buccal misoprostol route has the same effectiveness than the vaginal route but more gastrointestinal side effects (EL1, grade A). Between 7 and 9 LMP, it does not seem necessary to repeat misoprostol dose whereas it should be repeated beyond 9 SA (grade B). Between 9 and 14 LMP, the dose of 400μg misoprostol given either vaginally, buccally or sublingually should be repeated every 3hours if needed (with a maximum of 5 doses) (EL2, grade B). There is no strong evidence supporting routine antibiotic prophylaxis for medical abortion (professional agreement). Rare contraindications

  11. Mutations induced in plant breeding

    International Nuclear Information System (INIS)

    Barriga B, P.

    1984-01-01

    The most significant aspects of the use of ionizing radiations in plant breeding are reviewed. Aspects such as basic principles of mutation, expression and selection in obtention of mutants, methods for using induced mutations and sucess achieved with this methodology in plant breeding are reviewed. Results obtained in a program of induced mutation on wheat for high content of protein and lysine at the Universidad Austral de Chile are presented. (Author)

  12. Mutations induced in plant breeding

    Energy Technology Data Exchange (ETDEWEB)

    Barriga B, P. (Universidad Austral de Chile, Valdivia. Inst. de Produccion y Sanidad Vegetal)

    1984-10-01

    The most significant aspects of the use of ionizing radiations in plant breeding are reviewed. Aspects such as basic principles of mutation, expression and selection in obtention of mutants, methods for using induced mutations and sucess achieved with this methodology in plant breeding are reviewed. Results obtained in a program of induced mutation on wheat for high content of protein and lysine at the Universidad Austral de Chile are presented.

  13. Holographic Two-Photon Induced Photopolymerization

    Data.gov (United States)

    Federal Laboratory Consortium — Holographic two-photon-induced photopolymerization (HTPIP) offers distinct advantages over conventional one-photon-induced photopolymerization and current techniques...

  14. Mitochondrial Swelling Induced by Glutathione

    Science.gov (United States)

    Lehninger, Albert L.; Schneider, Marion

    1959-01-01

    Reduced glutathione, in concentrations approximating those occurring in intact rat liver, causes swelling of rat liver mitochondria in vitro which is different in kinetics and extent from that yielded by L-thyroxine. The effect is also given by cysteine, which is more active, and reduced coenzyme A, but not by L-ascorbate, cystine, or oxidized glutathione. The optimum pH is 6.5, whereas thyroxine-induced swelling is optimal at pH 7.5. The GSH-induced swelling is not inhibited by DNP or dicumarol, nor by high concentrations of sucrose, serum albumin, or polyvinylpyrrolidone, in contrast to thyroxine-induced swelling. ATP inhibits the GSH swelling, but ADP and AMP are ineffective. Mn-+ is a very potent inhibitor, but Mg++ is ineffective. Ethylenediaminetetraacetate is also an effective inhibitor of GSH-induced swelling. The respiratory inhibitors amytal and antimycin A do not inhibit the swelling action of GSH, but cyanide does; these findings are consistent with the view that the oxidation-reduction state of the respiratory chain between cytochrome c and oxygen is a determinant of GSH-induced swelling. Reversal of GSH-induced swelling by osmotic means or by ATP in KCl media could not be observed. Large losses of nucleotides and protein occur during the swelling by GSH, suggesting that the action is irreversible. The characteristically drastic swelling action of GSH could be prevented if L-thyroxine was also present in the medium. PMID:13630941

  15. Induced mutations in sesame breeding

    International Nuclear Information System (INIS)

    Ashri, A.

    2001-01-01

    The scope of induced mutations in sesame (Sesamum indicum L.) breeding is reviewed. So far in Egypt, India, Iraq, Rep. of Korea, and Sri Lanka, 14 officially released varieties have been developed through induced mutations: 12 directly and 2 through cross breeding (one using the 'dt45' induced mutant from Israel). For another variety released in China there are no details. The induced mutations approach was adopted primarily in order to obtain genetic variability that was not available in the germplasm collection. The mutagens commonly applied have been gamma rays, EMS and sodium azide. Sesame seeds can withstand high mutagen doses, and there are genotypic differences in sensitivity between varieties. The mutants induced in the above named countries and others include better yield, improved seed retention, determinate habit, modified plant architecture and size, more uniform and shorter maturation period, earliness, resistance to diseases, genic male sterility, seed coat color, higher oil content and modified fatty acids composition. Some of the induced mutants have already given rise to improved varieties, the breeding value of other mutants is now being assessed and still others can serve as useful markers in genetic studies and breeding programmes. (author)

  16. Victim-induced criminality.

    Science.gov (United States)

    Fooner, M

    1966-09-02

    about the probable effects on the administration of criminal justice. These are pragmatic problems; there is a third problem which may at this time seem speculative, but is, nevertheless, quite important. 3) To what extent will a particular proposal for victim compensation contribute to a temptation-opportunity pattern in victim behavior? In previous studies it has been pointed out that large numbers of our fellow Americans have tended to acquire casual money-handling habits-generically designated "carelessness"-which contribute to the national growth of criminality. How the victim helps the criminal was sketched in reports of those studies (10). It was made abundantly clear that human beings in our affluent society cannot be assumed to be prudent or self-protective against the hazards of crime. Even when the "victim" is not overtly acting to commit a crime-as in the case of the property owner who hires an arsonist-he often tempts the offender. Among the victims of burglary-statistically the most prevalent crime in the United States-are a substantial number of Americans who keep cash, jewelry, and other valuables carelessly at home or in hotel rooms to which the burglar has easy access through door or window. Victims of automobile theft-one of the fastest growing classes of crime-include drivers who leave the vehicle or its contents invitingly accessible to thieves. And so on with other classes of crime. As pointed out in previous studies, when victim behavior follows a temptation-opportunity pattern, it (i) contributes to a "climate of criminal inducements," (ii) adds to the economic resources available to criminal societies, and (iii) detracts from the ability of lawenforcement agencies to suppress the growth of crime.

  17. Protolichesterinic acid, isolated from the lichen Cetraria islandica, reduces LRRC8A expression and volume-sensitive release of organic osmolytes in human lung epithelial cancer cells

    DEFF Research Database (Denmark)

    Thorsteinsdottir, Unnur Arna; Thorsteinsdottir, Margret; Lambert, Ian Henry

    2016-01-01

    /mL, 24 h) has no effect on VSOAC. Hence, length of PA's fatty acid chain adds to γ-lactone's inhibitory action. 5-Lipoxygenase (5-LO) activity is essential for swelling-induced activation of VSOAC. PA has no effect on cellular concentration of leukotrienes (5-HETE/LTB4) under hypotonic conditions...

  18. Montelukast reduces asthma exacerbations in 2- to 5-year-old children with intermittent asthma

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Zielen, Stefen; Garcia-Garcia, María Luz

    2005-01-01

    The PREVIA study was designed to investigate the role of montelukast, a leukotriene receptor antagonist, in the prevention of viral-induced asthma exacerbations in children aged 2 to 5 years with a history of intermittent asthma symptoms. The study was a 12-month multicenter, double-blind, parall...

  19. Diet-induced obesity attenuates fasting-induced hyperphagia.

    Science.gov (United States)

    Briggs, D I; Lemus, M B; Kua, E; Andrews, Z B

    2011-07-01

    Obesity impairs arcuate (ARC) neuropeptide Y (NPY)/agouti-releated peptide (AgRP) neuronal function and renders these homeostatic neurones unresponsive to the orexigenic hormone ghrelin. In the present study, we investigated the effect of diet-induced obesity (DIO) on feeding behaviour, ARC neuronal activation and mRNA expression following another orexigenic stimulus, an overnight fast. We show that 9 weeks of high-fat feeding attenuates fasting-induced hyperphagia by suppressing ARC neuronal activation and hypothalamic NPY/AgRP mRNA expression. Thus, the lack of appropriate feeding responses in DIO mice to a fast is caused by failure ARC neurones to recognise and/or respond to orexigenic cues. We propose that fasting-induced hyperphagia is regulated not by homeostatic control of appetite in DIO mice, but rather by changes in the reward circuitry. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

  20. Sociocultural determinants of induced abortion.

    Science.gov (United States)

    Korejo, Razia; Noorani, Khurshid Jehan; Bhutta, Shereen

    2003-05-01

    To determine the frequency of induced abortion and identify the role of sociocultural factors contributing to termination of pregnancy and associated morbidity and mortality in hospital setting. Prospective observational study. The study was conducted in the Department of Obstetrics and Gynaecology, Jinnah Postgraduate Medical Centre, Karachi from January 1999 to June 2001. The patients who were admitted for induced abortion were interviewed in privacy. On condition of anonymity they were asked about the age, parity, family setup and relationships, with particular emphasis on sociocultural reasons and factors contributing to induction of abortion. Details of status of abortionist and methods used for termination of pregnancy, the resulting complications and their severity were recorded. Out of total admissions, 57(2.35%) gave history of induced abortion. All women belonged to low socioeconomic class and 59.6% of them were illiterate. Forty-three (75.5%) of these women had never practiced contraception. Twenty-four (42%) were grandmultiparae and did not want more children. In 29 women (50.9%) the decision for abortion had been supported by the husband. In 25 women (43.8%) abortion was carried out by Daiyan (traditional midwives). Serious complications like uterine perforation with or without bowel injury were encountered in 25 (43.8%) of these women. During the study period illegally induced abortion accounted for 6 (10.5%) maternal deaths. Prevalence of poverty, illiteracy, grand multiparity and non-practice of contraception are strong determinants of induced abortion.