Sample records for ketotifen

  1. Interaction of Ketotifen Fumarate with Anhydrous Theophylline in ...

    African Journals Online (AJOL)

    Purpose: The purpose of the present study was to investigate interaction between ketotifen fumarate and anhydrous theophylline in aqueous media of various pH. Methods: By using Job's continuous-variation analysis and Ardon's spectrophotomeric methods, the values of stability constants of theophylline with ketotifen ...

  2. Effects of ketotifen on human lymphocytes in vitro and in vivo

    NARCIS (Netherlands)

    Petrasch, S.; van Tits, L. J.; Motulsky, H. J.; Brodde, O. E.; Michel, M. C.


    The effects of the antiasthmatic drug ketotifen (CAS 34580-13-7) on human mononuclear leukocytes were studied in vitro and in vivo. In vitro ketotifen concentration-dependently inhibited mitogen-stimulated lymphocyte proliferation. High ketotifen concentrations also inhibited T-lymphocyte mitogen-

  3. Interaction of Ketotifen Fumarate with Anhydrous Theophylline in ...

    African Journals Online (AJOL)


    Theophylline in Simulated Gastric and Intestinal Media and Effect on ... However, following theophylline interaction with ketotifen, stability constant was < 1 at gastric pH (0.4 and 2.0) ..... from pH as low as stomach acid (pH 0.4 to 3) to as high ...

  4. Anti-Allergic Drugs Tranilast and Ketotifen Dose-Dependently Exert Mast Cell-Stabilizing Properties

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    Asuka Baba


    Full Text Available Background: Anti-allergic drugs, such as tranilast and ketotifen, inhibit the release of chemokines from mast cells. However, we know little about their direct effects on the exocytotic process of mast cells. Since exocytosis in mast cells can be monitored electrophysiologically by changes in the whole-cell membrane capacitance (Cm, the absence of such changes by these drugs indicates their mast cell-stabilizing properties. Methods: Employing the standard patch-clamp whole-cell recording technique in rat peritoneal mast cells, we examined the effects of tranilast and ketotifen on the Cm during exocytosis. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane. Results: Relatively lower concentrations of tranilast (100, 250 µM and ketotifen (1, 10 µM did not significantly affect the GTP-γ-S-induced increase in the Cm. However, higher concentrations of tranilast (500 µM, 1 mM and ketotifen (50, 100 µM almost totally suppressed the increase in the Cm, and washed out the trapping of the dye on the surface of the mast cells. Compared to tranilast, ketotifen required much lower doses to similarly inhibit the degranulation of mast cells or the increase in the Cm. Conclusions: This study provides electrophysiological evidence for the first time that tranilast and ketotifen dose-dependently inhibit the process of exocytosis, and that ketotifen is more potent than tranilast in stabilizing mast cells. The mast cell-stabilizing properties of these drugs may be attributed to their ability to counteract the plasma membrane deformation in degranulating mast cells.

  5. Ketotifen, a mast cell blocker improves sperm motility in asthenospermic infertile men

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    Nasrin Saharkhiz


    Full Text Available Aim: This study aimed to evaluate the efficacy of ketotifen on sperm motility of asthenospermic infertile men. Setting and Design: It is a prospective study designed in vivo. Materials and Methods: In this interventional experimental study, a total of 40 infertile couples with asthenospermic infertility factor undergoing assisted reproductive technology (ART cycles were enrolled. The couples were randomly assigned to one of two groups at the starting of the cycle. In control group (n = 20, the men did not receive Ketotifen, while in experiment group (n = 20, the men received oraly ketotifen (1 mg Bid for 2 months. Semen analysis, under optimal circumferences, was obtained prior to initiation of treatment. The second semen analysis was done 2-3 weeks after stopped ketotifen treatment and sperm motility was defined. Clinical pregnancy was identified as the presence of a fetal sac by vaginal ultrasound examination. Statistical Analysis Used: All data are expressed as the mean ± standard error of mean (SEM. t test was used for comparing the data of the control and treated groups. Results: The mean sperm motility increased significantly (from 16.7% to 21.4% after ketotifen treatment (P < 0.001. This sperm motility improvement was more pronounced in the primary infertility cases (P < 0.003. The rate of pregnancy was 12.5% in infertile couples that their men receiving 1 mg/twice a day ketotifen. In 52% of infertile men′s semen, the percentage of sperm motility was increased from 5% to 35% and this sperm motility improvement was also observed in 33% of necrospermia (0% motility cases. Conclusion: These results suggest that ketotifen may represent as a novel therapeutic approach to improve sperm motility in the infertile men with cause of asthenospermia or necrospermia.

  6. The effect of ketotifen on inflammatory markers in allergic conjunctivitis: an open, uncontrolled study

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    Gagliardi Julio


    Full Text Available Abstract Background The efficacy and safety of ketotifen eye drop treatment in allergic conjunctivitis (AC management is perfectly known by several studies, but the mechanism of action at the biochemical levels is poorly understood so we decided to perform an open, uncontrolled study in order to investigate the effect of the topical administration of ketotifen fumarate 0.05% on biochemical markers of inflammation on conjunctival cells in patients with AC. Methods Nineteen patients with symptoms and signs of AC (itching, discharge, burning, redness, increase in the watery discharge, swelling and follicles and with a history of allergy were prescribed with two daily instillation of one drop of eyewash ketotifen fumarate 0,05% in both eyes during thirty days. They were studied by measuring clinical and immunologic parameters. Results Ketotifen fumarate treatment significantly reduced the total symptoms and signs score for each patient as well as each symptoms and signs at all time points compared with day 0 (p Conclusion Ketotifen besides the well-known effect in reducing signs and symptoms of AC significantly diminished production of eotaxin and expression of CD29 by epithelial cells in patients with seasonal AC.

  7. Comparing the effects of ketotifen fumarate eye drops and ketotifen oral pills on symptom severity and quality of life in patients with allergic rhinitis: a double-blind randomized clinical trial. (United States)

    Akhavan, Asghar; Karimi-Sari, Hamidreza; Khosravi, Mohammad Hossein; Arefzadeh, Esmaeil; Yavarahmadi, Mohammadhosein


    Allergic rhinitis is a chronic inflammatory disease of nasal mucosa. Previous studies have shown the therapeutic effects of ketotifen eye drops on allergic conjunctivitis and rhinitis patients. This study was designed to compare the effects of ketotifen drops and oral ketotifen pills on symptoms and quality of life in allergic rhinitis patients. In this double-blind randomized clinical trial, patients with mild allergic rhinitis who were referred to the allergy clinic of Baqiyatallah Hospital from March to April 2014 were randomly allocated to 2 groups; the first group received ketotifen drops (1 drop every 12 hours) with placebo pills (2 pills daily), and the second group received placebo eye drops with ketotifen pills for 4 weeks. Symptoms (sneezing, runny nose, itching, and nasal obstruction) severity were examined and Rhinitis Quality of Life Questionnaire (RQLQ) scores were evaluated in the second and fourth weeks. A total of 140 patients were evaluated in 2 groups. The mean age was 30.33 years. There were no significant differences in demographic data between the groups (p > 0.05). Both groups showed a significant improvement in rhinorrhea, nasal congestion, nasal itching, coughing, sneezing, RQLQ, and nasal smear eosinophil percent compared to baseline amounts (p < 0.05). Improvements were significantly more in the drops group (p < 0.05). Because of the absence of systemic complications in ketotifen eye drops in patients with allergic rhinitis and their easy availability in Iran, using this medication instead of systemic therapies is suggested. Nevertheless, more studies are required to evaluate the long-term effects of using this drug and the recurrence rate of symptoms. © 2015 ARS-AAOA, LLC.

  8. Protective effect of ketotifen and disodium cromoglycate against bronchoconstriction induced by aspirin, benzoic acid or tartrazine in intolerant asthmatics. (United States)

    Wüthrich, B


    Oral challenge tests with acetylsalicylic acid, tartrazine or benzoic acid were performed in 7 intolerant asthmatic patients after a 3-day treatment with either orally taken ketotifen (1 mg twice daily) or inhaled disodium cromoglycate (20 mg four times daily) at random. Protection was noted with ketotifen in 5, with DSCG in 3 patients. On the evaluation of the mean percentage of the maximum decline in the forced expiratory volume in 1 sec (FEV1) only ketotifen afforded significant protection statistically (p less than 0.05). All the intolerant asthmatics studies showed, as an immunological abnormity, a slight, but significant decrease of the C1-inhibitor levels. Moreover, in three out of these the alpha 1-antitrypsin serum values were under the lower normal range.

  9. Comparison of preservative-free ketotifen fumarate and preserved olopatadine hydrochloride eye drops in the treatment of moderate to severe seasonal allergic conjunctivitis. (United States)

    Mortemousque, B; Bourcier, T; Khairallah, M; Messaoud, R; Brignole-Baudouin, F; Renault, D; Rebika, H; Brémond-Gignac, D


    To compare preservative-free ketotifen 0.025% ophthalmic solution to olopatadine 0.1% ophthalmic solution in with the treatment of seasonal allergic conjunctivitis (SAC) in clinical practice. This was a comparative, randomised, investigator-masked, pilot clinical study in adult patients with documented history of SAC and presenting with moderate to severe itching and conjunctival hyperemia. Eligible patients initiated either ketotifen or olopatadine treatment at a dose of one drop twice daily for 28days. The resolution of ocular signs and symptoms was assessed on day 7 and day 28. Itching was also assessed within 15minutes following the first instillation (day 0). Conjunctival impression cytology was performed at each visit to assess the evolution of ICAM-1 expression (day 0, 7 and 28). Seventy-five patients were randomised (ketotifen: 38 patients; olopatadine: 37 patients). At day 28, the composite score for primary criteria (itching, tearing, and conjunctival hyperemia) improved from 6.8±1.2 to 0.9±1.0 in the Ketotifen group, without statistically significant difference between treatment groups (P=0.67). There was no relevant difference between treatment groups in other efficacy parameters, except a trend for a more rapid resolution of conjunctival hyperemia in the Ketotifen group. Both drugs were well tolerated, with a trend for a better tolerability reported by patients on ketotifen compared to those on olopatadine at day 7 (P=0.054). A rapid and comparable improvement in SAC was achieved after 28days of treatment with both preservative-free ketotifen and preserved olopatadine ophthalmic solutions, with a slightly better ocular tolerance with unpreserved ketotifen 0.025% eye drops. Copyright © 2013. Published by Elsevier Masson SAS.

  10. Ketotifen Ophthalmic (United States)

    ... class of medications called antihistamines. It works by blocking histamine, a substance in the body that causes ... the remaining fingers of that hand against your face. While looking up, gently squeeze the dropper so ...

  11. Potentiometric Determination of Ketotifen Fumarate in Pharmaceutical Preparations and Urine Using Carbon Paste and PVC Membrane Selective Electrodes

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    Eman Y. Z. Frag


    Full Text Available This study compares between unmodified carbon paste (CPE; the paste has no ion pair and polyvinyl chloride (PVC membrane selective electrodes that were used in potentiometric determination of ketotifen fumarate (KTF, where sodium tetraphenylborate (NaTPB was used as titrant. The performance characteristics of these sensors were evaluated according to IUPAC recommendations which reveal a fast, stable, and linear response for KTF over the concentration range of 10−7 to 10−2 mol L−1. The electrodes show Nernstian slope value of 52.51±0.20 and 51.51±0.25 mV decade−1 for CPE and PVC membrane electrodes at 30∘C, respectively. The potential is nearly stable over the pH range 3.0–6.0 and 2.0–7.0 for CPE and PVC membrane electrodes, respectively. Selectivity coefficient values towards different inorganic cations, sugars, and amino acids reflect high selectivity of the prepared electrodes. The electrodes responses at different temperatures were also studied, and long operational lifetime of 12 and 5 weeks for CPE and PVC membrane electrodes, respectively, were found. These are used for determination of ketotifen fumarate using potentiometric titration, calibration, and standard addition methods in pure samples, its pharmaceutical preparations (Zaditen tablets, and biological fluid (urine. The direct potentiometric determination of KTF using the proposed sensors gave recoveries % of 98.97±0.53 and 98.62±0.74 with RSD 1.42 and 0.63% for CPE and PVC membrane selective electrodes, respectively. Validation of the method shows suitability of the proposed sensors for use in quality control assessment of KTF. The obtained results were in a good agreement with those obtained using the reported spectrophotometric method.

  12. Potentiometric determination of ketotifen fumarate in pharmaceutical preparations and urine using carbon paste and PVC membrane selective electrodes. (United States)

    Frag, Eman Y Z; Mohamed, Gehad G; Khalil, Mohamed M; Hwehy, Mohammad M A


    This study compares between unmodified carbon paste (CPE; the paste has no ion pair) and polyvinyl chloride (PVC) membrane selective electrodes that were used in potentiometric determination of ketotifen fumarate (KTF), where sodium tetraphenylborate (NaTPB) was used as titrant. The performance characteristics of these sensors were evaluated according to IUPAC recommendations which reveal a fast, stable, and linear response for KTF over the concentration range of 10(-7) to 10(-2) mol L(-1). The electrodes show Nernstian slope value of 52.51 ± 0.20 and 51.51 ± 0.25 mV decade(-1) for CPE and PVC membrane electrodes at 30°C, respectively. The potential is nearly stable over the pH range 3.0-6.0 and 2.0-7.0 for CPE and PVC membrane electrodes, respectively. Selectivity coefficient values towards different inorganic cations, sugars, and amino acids reflect high selectivity of the prepared electrodes. The electrodes responses at different temperatures were also studied, and long operational lifetime of 12 and 5 weeks for CPE and PVC membrane electrodes, respectively, were found. These are used for determination of ketotifen fumarate using potentiometric titration, calibration, and standard addition methods in pure samples, its pharmaceutical preparations (Zaditen tablets), and biological fluid (urine). The direct potentiometric determination of KTF using the proposed sensors gave recoveries % of 98.97 ± 0.53 and 98.62 ± 0.74 with RSD 1.42 and 0.63% for CPE and PVC membrane selective electrodes, respectively. Validation of the method shows suitability of the proposed sensors for use in quality control assessment of KTF. The obtained results were in a good agreement with those obtained using the reported spectrophotometric method.

  13. Salmeterol versus slow-release theophylline combined with ketotifen in nocturnal asthma: a multicentre trial. French Multicentre Study Group. (United States)

    Muir, J F; Bertin, L; Georges, D


    We wished to assess the efficacy of inhaled salmeterol (SML; 50 micrograms b.i.d.) compared to a combination of slow-release theophylline and ketotifen p.o. (TK; T 300 mg+K 1 mg b.i.d.) for the treatment of nocturnal asthma. Ninety six patients with nocturnal asthma, (forced expiratory volume in one second (FEV1) 60-90% of predicted value, reversibility > or = 15%, at least two nocturnal awakenings per week) were eligible for a multicentre, double-blind, double-dummy cross-over study (14-day run-in, two successive 28-day treatment periods). Efficacy was assessed as success/failure, success being defined as the complete disappearance of nocturnal symptoms/awakening during the last week of each treatment period. There was a statistically significant difference between SML and TK for this criterion: 46% and 39% success with SML during periods I (first 28-day period) and II (following the cross-over), compared to only 15% and 26% with TK, respectively (p < 0.01). SML was also significantly better for the other criteria (lung function, rescue salbutamol intake during day and night). Side-effects were five times less frequent in SML-treated patients (p < 0.004). Efficacy and tolerance of SML were obviously far better than those of TK in patients with nocturnal asthma.

  14. Diseño de una formulación de ketotifeno 0,025 % colirio Design of a Ketotifen formula: 0.025 % eyedrops

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    Yenilen Troche Concepción


    Full Text Available El colirio de ketotifeno se indica para aliviar los signos y síntomas de las conjuntivitis alérgicas, por ser este un potente antihistamínico H1 que muestra cierta capacidad para inhibir la liberación de histamina y otros mediadores en mastocitos. El objetivo del presente trabajo consistió en realizar el desarrollo tecnológico del colirio de ketotifeno 0,025 %, de producción nacional teniendo en cuenta que es un medicamento muy utilizado en la "Operación Milagro", en la cual participa la República de Cuba, para lo que se hace un diseño y los estudios de preformulación. Se estudió además, las especificaciones de calidad de la formulación seleccionada, la estabilidad del producto y el tiempo de vigencia de este. Se realizó el estudio de estabilidad acelerado y por vida de estante, para lo cual se emplearon 3 lotes del producto a escala piloto. El colirio resultó estable física, química y microbiológicamente envasado en frascos de polietileno de baja densidad, por espacio de 12 meses a temperatura ambienteThe Ketotifen eyedrops is prescribed to relieve the signs and symptoms of allergic conjunctivitis due to it is a powerful H1 antihistaminic with certain ability to inhibit the histamine release and other mediators in the case of mast cells. The aim of present paper was to perform the technological development of 0.025 % eyedrops Ketotifen of national production considering that it is a drug very used in the "Operación Milagro" with participation of the Republic of Cuba and with its own design and the pre-formula. Also, we studied the selected formula specifications, the product stability and its expiry date. An accelerated stability study was conducted and by shelf life using 3 batches of pilot scale product. The eyedrops was physically, chemically and microbiologically stable when it is bottling in low-density polyethylene flasks during 12 months at room temperature.

  15. Generic selection criteria for safety and patient benefit [V]: Comparing the pharmaceutical properties and patient usability of original and generic nasal spray containing ketotifen fumarate. (United States)

    Wada, Yuko; Ami, Shyoko; Nozawa, Mitsuru; Goto, Miho; Shimokawa, Ken-Ichi; Ishii, Fumiyoshi

    The pH, osmotic pressure (cryoscopy), viscosity, squeeze force, spray angle, and spraying frequency of nasal spray containing ketotifen fumarate (1 brand-name product and 8 generic products) were measured. Based on the results of pH measurement, all products were weakly acidic (4.0 to 5.1). For all products, the osmotic pressure ratio to physiological saline was approximately 1. The viscosity of various products ranged from approximately 1.0 to 1.5 mPa·s. The spray angle of drug solution differed among the products: minimum, 46 degrees (Sawai and Fusachol); and maximum, 68.7 degrees (Sekiton). In particular, TOA, Sawai, Fusachol, and TYK showed significantly smaller angles compared to Zaditen (brand-name product). Container properties varied among the products: minimum squeeze force, 19.0 N (Sekiton); and maximum squeeze force, 43.1 N (Sawai). Based on these results, although all the above products are identical in dosage form and active ingredient, the differences in pharmaceutical properties, such as container operations and drug-solution spraying/attachment, may markedly influence patients' subjective opinions.

  16. Prevention of Posttraumatic Contractures with Ketotifen (PERK) (United States)


    Disability Arm, Shoulder, Hand; Oxford Elbow Score; radiographs; reoperation 2 – 52 weeks post-randomization. Military Benefit and Clinical Impact: A...disengagement from the project for more than three months, or a 25 percent reduction in his or her time devoted to the project. d. The inclusion of direct...FINAL_OES_English_UK_Sample-1 Disability of the Arm, Shoulder and Hand (DASH) Questionnaire Case Report Forms, 1.0, July 24, 2017 PERK II Protocol V1.0 20170731, 1.0

  17. Development and Validation of a Stability-Indicating LC-UV Method ...

    African Journals Online (AJOL)

    Keywords: Ketotifen, Cetirizine, Stability indicating method, Stressed conditions, Validation. Tropical ... in biological fluids [13] are also reported. Stability indicating HPLC method is reported for ketotifen where drug is ..... paracetamol, cetirizine.

  18. West syndrome associated with administration of a histamine H1 antagonist, oxatomide. (United States)

    Yamashita, Yushiro; Isagai, Takeo; Seki, Yoshitaka; Ohya, Takashi; Nagamitsu, Shinichiro; Matsuishi, Toyojiro


    We report a 4-month-old female infant who developed West syndrome eleven days after administration of a histamine H1 antagonist, oxatomide, for atopic dermatitis. It has been reported that some histamine H1 antagonists induce seizures in epileptic patients. The age, the interval between oxatomide administration, and the onset of West syndrome and its clinical course were similar to two previously reported 3-month-old infants with West syndrome associated with ketotifen administration. We should be cautious in using the histamine H1 antagonists, oxatomide and ketotifen, in young infants because such agents could potentially disturb the anticonvulsive central histaminergic system.

  19. Development and Validation of a Stability-Indicating LC-UV Method ...

    African Journals Online (AJOL)

    Development and Validation of a Stability-Indicating LC-UV Method for Simultaneous Determination of Ketotifen and Cetirizine in Pharmaceutical Dosage Forms. ... 5 μm) using an isocratic mobile phase that consisted of acetonitrile and 10 mM disodium hydrogen phosphate buffer (pH 6.5) in a ratio of 45:55 % v/v at a flow ...

  20. Mast cell stabilization decreases cardiomyocyte and LV function in dogs with isolated mitral regurgitation. (United States)

    Pat, Betty; Killingsworth, Cheryl; Chen, Yuanwen; Gladden, James D; Walcott, Greg; Powell, Pamela C; Denney, Thomas; Gupta, Himanshu; Desai, Ravi; Tillson, Michael; Dillon, A Ray; Dell'italia, Louis J


    Mast cells are increased in isolated mitral regurgitation (MR) in the dog and may mediate extracellular matrix loss and left ventricular (LV) dilatation. We tested the hypothesis that mast cell stabilization would attenuate LV remodeling and improve function in the MR dog. MR was induced in adult dogs randomized to no treatment (MR, n = 5) or to the mast cell stabilizer, ketotifen (MR + MCS, n = 4) for 4 months. LV hemodynamics were obtained at baseline and after 4 months of MR and magnetic resonance imaging (MRI) was performed at sacrifice. MRI-derived, serial, short-axis LV end-diastolic (ED) and end-systolic (ES) volumes, LVED volume/mass ratio, and LV 3-dimensional radius/wall thickness were increased in MR and MR + MCS dogs compared with normal dogs (n = 6) (P < .05). Interstitial collagen was decreased by 30% in both MR and MR + MCS versus normal dogs (P < .05). LV contractility by LV maximum time-varying elastance was significantly depressed in MR and MR + MCS dogs. Furthermore, cardiomyocyte fractional shortening was decreased in MR versus normal dogs and further depressed in MR + MCS dogs (P < .05). In vitro administration of ketotifen to normal cardiomyocytes also significantly decreased fractional shortening and calcium transients. Chronic mast cell stabilization did not attenuate eccentric LV remodeling or collagen loss in MR. However, MCS therapy had a detrimental effect on LV function because of a direct negative inotropic effect on cardiomyocyte function. Published by Elsevier Inc.

  1. Ketotifeno: un antialérgico efectivo

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    Carlos Coronel Carbajal


    Full Text Available El ketotifeno es un medicamento ampliamente usado en el tratamiento de las enfermedades alérgicas, pero con discrepancias respecto a su efectividad. Se realizó un estudio descriptivo en una muestra de 87 pacientes en las edades comprendidas entre 6 meses y 15 años, en el Hospital General Docente «Armando Enrique Cardoso» en el período comprendido entre noviembre de 1998 y enero del 2000. El objetivo fue evaluar la efectividad del ketotifeno en el tratamiento de las enfermedades alérgicas, así como reconocer sus principales efectos colaterales y el tiempo en aparecer la mejoría clínica. Los resultados obtenidos al aplicar un formulario se presentan en 5 tablas y se expresan en tanto por cientos. Se llegaron a las siguientes conclusiones: el ketotifeno resultó efectivo en el 72,6 % de los pacientes, en el 71,3 %, este medicamento fue efectivo en la prevención de las exacerbaciones de asma bronquial, sólo el 25,2 % manifestó algún efecto adverso y el tiempo promedio en notar el control fue entre 4 y 8 semanas en el 58,7 % de los pacientes.Ketotifen is a drug that is widely used in the treatment of allergic diseases, but there are discrepancies in relation to its effectiveness. A descriptive study of a sample of 87 patients between 6 months old and and 15 years old was conducted at "Armando Enrique Cardoso" General Teaching Hospital from November, 1998, to January, 2000, aimed at evaluating the effectiveness of ketotifen in the treatment of allergic diseases as well as to recognize its main side effects and the moment when the clinical improvement begins. The results obtained after applying a formulary are shown in 5 tables and are expressed in percentage. The following conclusions were reached: ketotifen proved to be effective in 72.6 % of the patients, this drug was effective in the prevention of aggravations of bronchial asthma in 71.3 %, only 25.2 % suffered from some adverse effect and the average time to control the disease was

  2. Effect of Intervention in Mast Cell Function Before Reperfusion on Renal Ischemia-Reperfusion Injury in Rats

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    Fei Tong


    Full Text Available Background/Aims: Mast cells are sparsely distributed in the kidneys under normal conditions; however, the number of mast cells increases dramatically during renal ischemia/reperfusion injury (RI/RI. When mast cells are stimulated, numerous mediators are released, and under pathological conditions, they produce a wide range of biological effects. The aim of this study was to investigate the effect of intervention in mast cell function before reperfusion on RI/RI. Methods: Sprague-Dawley (SD rats (n=50 were randomized into five groups: sham group, ischemia/reperfusion (I/R group, cromolyn sodium treatment group (CS+I/R group, ketotifen treatment group (K+I/Rgroup, and compound 48/80 treatment group (C+I/R group. I/R injury was induced by bilateral renal artery and vein occlusion for 45 min followed by 24 h of reperfusion. The agents were intravenously administered 5 min before reperfusion through the tail vein. The serum levels of blood urea nitrogen(BUN, serum creatinine (Scr and histamine and the kidney levels of malondialdehyde (MDA, superoxide dismutase (SOD, tumor necrosis factor α (TNF-α and interleukin-6 (IL-6 were assessed. The expression of intracellular adhesion molecule-1 (ICAM-1 in renal tissue was also measured. Results: I/R injury resulted in severe renal injury, as demonstrated by a large increase in injury scores; serum levels of BUN, Scr and histamine; and kidney levels of MDA, TNF-α, and IL-6; this was accompanied by reduced SOD activity and upregulated ICAM-1 expression. Treatment with cromolyn sodium or ketotifen markedly alleviated I/R-mediated kidney injury, whereas compound 48/80 further aggravated kidney injury. Conclusion: Intervention in mast cell activity prior to reperfusionhas a strong effect on RI/RI.

  3. Transcriptional Profiling Confirms the Therapeutic Effects of Mast Cell Stabilization in a Dengue Disease Model. (United States)

    Morrison, Juliet; Rathore, Abhay P S; Mantri, Chinmay K; Aman, Siti A B; Nishida, Andrew; St John, Ashley L


    There are no approved therapeutics for the treatment of dengue disease despite the global prevalence of dengue virus (DENV) and its mosquito vectors. DENV infections can lead to vascular complications, hemorrhage, and shock due to the ability of DENV to infect a variety of immune and nonimmune cell populations. Increasingly, studies have implicated the host response as a major contributor to severe disease. Inflammatory products of various cell types, including responding T cells, mast cells (MCs), and infected monocytes, can contribute to immune pathology. In this study, we show that the host response to DENV infection in immunocompetent mice recapitulates transcriptional changes that have been described in human studies. We found that DENV infection strongly induced metabolic dysregulation, complement signaling, and inflammation. DENV also affected the immune cell content of the spleen and liver, enhancing NK, NKT, and CD8 + T cell activation. The MC-stabilizing drug ketotifen reversed many of these responses without suppressing memory T cell formation and induced additional changes in the transcriptome and immune cell composition of the spleen, consistent with reduced inflammation. This study provides a global transcriptional map of immune activation in DENV target organs of an immunocompetent host and supports the further development of targeted immunomodulatory strategies to treat DENV disease. IMPORTANCE Dengue virus (DENV), which causes febrile illness, is transmitted by mosquito vectors throughout tropical and subtropical regions of the world. Symptoms of DENV infection involve damage to blood vessels and, in rare cases, hemorrhage and shock. Currently, there are no targeted therapies to treat DENV infection, but it is thought that drugs that target the host immune response may be effective in limiting symptoms that result from excessive inflammation. In this study, we measured the host transcriptional response to infection in multiple DENV target organs

  4. Preserved and unpreserved 12 anti-allergic ophthalmic solutions and ocular surface toxicity: in vitro assessment in four cultured corneal and conjunctival epithelial cell lines. (United States)

    Ayaki, Masahiko; Iwasawa, Atsuo; Yaguchi, Shigeo; Koide, Ryohei


    In the present study, we evaluated the cytotoxicity of anti-allergic ophthalmic solutions in cultured corneal and conjunctival cells, namely SIRC (rabbit corneal epithelium), BCE C/D-1b (bovine corneal epithelial cells), RC-1 (rabbit corneal epithelium), and Chang (human conjunctival cells). The viability of cell cultures was determined following the exposure of cells to 12 commercially available anti-allergic ophthalmic solutions for varying exposure times and at various dilutions using the MTT and neutral red assays. The cell viability score (CVS) was used to compare the toxicity of different drugs. Based on CVS data, the order of cell viability after exposure to the drugs was Zepelin ≥ Tramelas PF ≥ Cumorol PF ≥ Ketotifen PF ≥ Eyevinal = Fumarton ≥ Cumorol > Intal ≥ Rizaben ≥ Tramelas ≥ Patanol Livostin. In conclusion, cell viability was mostly affected by the concentration of benzalkonium chloride rather than the active component and/or the anti-allergic action of the drug. The CVS was useful in comparing the toxicity of different drugs.

  5. Inhibition of allergic dermal inflammation by the novel imidazopyridazine derivative TAK-427 in a guinea pig experimental model of eczema. (United States)

    Fukuda, Shigeru; Midoro, Katsuo; Kamei, Takayuki; Gyoten, Michiyo; Kawano, Yasuhiko; Ashida, Yasuko; Nagaya, Hideaki


    Antigen challenge by patch ovalbumin emulsion induced an eczema-like skin lesion in epicutaneously sensitized guinea pigs. Diseased skin sites were macroscopically characterized by manifestations of dermatitis, such as erythema, edema, and papules, and microscopically characterized by acanthosis, spongiosis, and dermal infiltration by eosinophils. Using such lesions as a model of eczema, we evaluated the potential value of TAK-427 [2-[6-[[3-[4-(diphenylmethoxy)piperidino]propyl]amino] imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionic acid dihydrate] as a therapeutic agent for atopic dermatitis by comparing it with dexamethasone and antihistamines. TAK-427 (0.3-30 mg/kg, p.o.) and dexamethasone (3 and 10 mg/kg, p.o.) inhibited eosinophil infiltration into the skin and ameliorated the dermatitis manifestations and epidermal damage. By contrast, none of the antihistamines tested (azelastine, ketotifen, terfenadine, and cetirizine) suppressed the eosinophil infiltration or dermatitis manifestations. To elucidate the mechanism by which TAK-427 inhibited the development of eczema, we investigated cytokine expression in the affected skin. Both TAK-427 and dexamethasone suppressed the increased mRNA expression of interleukin (IL)-13, granulocyte-macrophage colony-stimulating factor, IL-1alpha, tumor necrosis factor-alpha, interferon-gamma, and IL-8, but not IL-10, suggesting that TAK-427 inhibits allergic inflammation of the skin leading to the development of eczema by inhibiting the expression of proinflammatory cytokines after antigen challenge.

  6. Olopatadine Suppresses the Migration of THP-1 Monocytes Induced by S100A12 Protein

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    Full Text Available Olopatadine hydrochloride (olopatadine is an antiallergic drug with histamine H 1 receptor antagonistic activity. Recently, olopatadine has been shown to bind to S100A12 which is a member of the S100 family of calcium-binding proteins, and exerts multiple proinflammatory activities including chemotaxis for monocytes and neutrophils. In this study, we examined the possibility that the interaction of olopatadine with S100A12 inhibits the proinflammatory effects of S100A12. Pretreatment of olopatadine with S100A12 reduced migration of THP-1, a monocyte cell line, induced by S100A12 alone, but did not affect recombinant human regulated upon activation, normal T cell expressed and secreted (RANTES-induced migration. Amlexanox, which also binds to S100A12, inhibited the THP-1 migration induced by S100A12. However, ketotifen, another histamine H 1 receptor antagonist, had little effect on the activity of S100A12. These results suggest that olopatadine has a new mechanism of action, that is, suppression of the function of S100A12, in addition to histamine H 1 receptor antagonistic activity.

  7. Anti-allergic properties of Mangifera indica L. extract (Vimang) and contribution of its glucosylxanthone mangiferin. (United States)

    Rivera, Dagmar García; Balmaseda, Ivones Hernández; León, Alina Alvarez; Hernández, Belkis Cancio; Montiel, Lucía Márquez; Garrido, Gabino Garrido; Cuzzocrea, Salvatore; Hernández, René Delgado


    Vimang is the brand name of formulations containing an extract of Mangifera indica L., ethnopharmacologically used in Cuba for the treatment of some immunopathological disorders, including bronchial asthma, atopic dermatitis and other allergic diseases. However, the effects of Vimang on allergic response have not been reported until now. In this study, the effects of Vimang and mangiferin, a C-glucosylxanthone isolated from the extract, on different parameters of allergic response are reported. Vimang and mangiferin showed a significant dose-dependent inhibition of IgE production in mice and anaphylaxis reaction in rats, histamine-induced vascular permeability and the histamine release induced by compound 48/80 from rat mast cells, and of lymphocyte proliferative response as evidence of the reduction of the amount of B and T lymphocytes able to contribute to allergic response. In these experiments, ketotifen, promethazine and disodium cromoglicate were used as reference drugs. Furthermore, we demonstrated that Vimang had an effect on an in-vivo model of inflammatory allergy mediated by mast cells. These results constitute the first report of the anti-allergic properties of Vimang on allergic models, as well as suggesting that this natural extract could be successfully used in the treatment of allergic disorders. Mangiferin, the major compound of Vimang, contributes to the anti-allergic effects of the extract.

  8. Effects of Bidens pilosa L. var. radiata SCHERFF treated with enzyme on histamine-induced contraction of guinea pig ileum and on histamine release from mast cells. (United States)

    Matsumoto, Takayuki; Horiuchi, Masako; Kamata, Katsuo; Seyama, Yoshiyuki


    The medical mechanism against type I allergies is to block the release or production of chemical mediators from mast cells or to block the H(1)-receptor signaling. We previously reported that the anti-allergic action of the dry powder from Bidens pilosa L. var. radiata SCHERFF treated with the enzyme cellulosine (eMMBP) was dependent on the inhibition of histamine release from mast cells. Here, we investigate that the effect of fractions in eMMBP on the histamine-induced contraction in guinea pig ileum and on the release of histamine in rat peritoneal mast cells. The histamine-induced contraction in guinea pig ileum is dose-dependently inhibited by ketotifen, an antagonist of H(1)-receptor. Fractions contained caffeic acid, caffeoylquinic acid and fractions contained flavonoids such as hyperin and isoquercitrin in eMMBP inhibit histamine release from mast cells, but only flavonoids such as hyperin, isoquercitrin and rutin suppress the histamine-induced contraction in guinea pig ileum. Moreover, the histamine-induced contraction was not affected by caffeic acid, however, such contraction was significantly inhibited by rutin. These results suggest that the primary antagonists of H(1)- receptor are different from the components in eMMBP that inhibit histamine release, and that these components participate in the anti-allergic activity of eMMBP.

  9. [Management of asthma in a context of ambulatory pediatrics: relevance and possibility to avoid the problems. Gruppo de lavoro pediatri dell'Abruzzo Basilicata e Puglia]. (United States)

    Misticoni, G; Marchetti, F; D'Andrea, N


    41 pediatricians agreed to register on a very simple form, all the cases of children affected by bronchial asthma visited in their clinic during october 1993. The data included basic information related to the therapy prescribed, its duration, a judgement on the efficacy of symptoms control and the main problems encountered with the children and their families. 237 cases were reported (mean age 4.6 year, range 2 months-13 years). 80% of children were monitored by the pediatrician; 47% had allergic reactions. The main drug used for profilaxis is ketotifen, a compound without documented efficacy; the main route for drug administration (especially during acute attacks) is by mouth, instead of by aerosol, evidencing problems in the health education on practical skills. In fact the main problems encountered by doctors are related to the communication with patients and families. This survey represents also a research model for involving health care providers and easily and quickly obtaining a useful, methodologically sound and interesting picture of everyday practice.

  10. Evidence for the role of histaminergic pathways in neuroprotective mechanism of ischemic postconditioning in mice. (United States)

    Kaur, Indresh; Kumar, Amit; Jaggi, Amteshwar S; Singh, Nirmal


    The present study has been designed to investigate the possible role of histaminergic pathway in neuroprotective mechanism of ischemic postconditioning (iPoCo). Bilateral carotid artery occlusion (BCAO) for 12 min followed by reperfusion for 24 h was employed to produce I/R-induced cerebral injury in National Institutes of Health mice mice. iPoCo involving three episodes of carotid artery occlusion and reperfusion of 10 sec each was instituted immediately after BCAO just before prolonged reperfusion. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using Morris water maze test. Rotarod test, inclined beam-walking test, and neurological severity score (NSS) were performed to assess motor incoordination and sensorimotor abilities. Brain acetylcholine esterase (AChE) activity, brain myeloperoxidase (MPO) activity, brain thiobarbituric acid-reactive species (TBARS), and glutathione level (GSH) were also estimated. BCAO produced a significant rise in cerebral infarct size and NSS along with impairment of memory and motor coordination and biochemical alteration (↑AChE, ↑MPO ↓GSH, and ↑TBARS). iPoCo attenuated the deleterious effect of BCAO on infarct size, memory, NSS, motor coordination, and biochemical markers. Pretreatment of carnosine (a histamine [HA] precursor) potentiated the neuroprotective effects of iPoCo, whereas pretreatment of ketotifen (HA H1 receptor blocker and mast cell stabilizer) abolished the protective effects of iPoCo as well as that of carnosine on iPoCo. It may be concluded that neuroprotective effect of iPoCo probably involves activation of histaminergic pathways. © 2017 Société Française de Pharmacologie et de Thérapeutique.

  11. [Treatment of chronic idiopathic urticaria unresponsive to type 1 antihistamines in monotherapy]. (United States)

    Mateus, C


    The chronic idiopathic urticaria treatment is a difficult and often frustrating problem for physicians. Due to the lack of definitive medical therapeutic programs to relieve the symptoms and prevent from their recurrence, several pharmacologic approaches to the management of chronic idiopathic urticaria are proposed. The chronic urticaria pharmacologic therapy is therefore fit to abrogate effects of histamine and other mediators on cutaneous vasculature and inflammatory cells that participate in the pathogenesis of the urticaria. The most common approach is to avoid all aggravating factors and to block histamine. The mainstay therapy is the H1 antihistamines. A significant number of patients may remain unresponsive even after an increase in the dose or a change in the type of H1 antihistaminic drug. In these cases, several therapies can be associated: combinations of H1 antihistamines, nonsedating one tablet (morning) and one sedating (evening), this approach is very usual but no study has confirmed it rational; addition an H2 antagonist to the previous treatment for some patients may improve control of their symptoms; alternatively, the tricyclic antidepressant, Doxepin is usually prescribed. The results of other drugs reported in the literature is unpredictable, to include them in a strategy therapy. The results with Badrenergic agents, nifedipine, ketotifen, leukotriene antagonists and tranexamic acid are variable and don't appear better than those with H1 antagonists. The efficiency of danazol has to be confirmed by other controlled studies. Warfarin, sulfasalazine and ultraviolet radiation have been used apparently successfully, but no controlled study has been published. Only when the above treatments have failed then immunosuppresive therapies, intravenous immunoglobulin and plasmapheresis can be proposed for chronic idiopathic urticaria.

  12. Food-dependent exercise-induced anaphylaxis with a high level of plasma noradrenaline. (United States)

    Kato, Yukihiko; Nagai, Ayako; Saito, Masuyoshi; Ito, Tomonobu; Koga, Michiyuki; Tsuboi, Ryoji


    Ingesting certain foods sometimes triggers anaphylaxis when followed by exercise (food-dependent exercise-induced anaphylaxis, FDEIA). Specific food-induced mucocutaneous urticaria may also progress to anaphylaxis (oral allergy syndrome, OAS). A positive skin test and/or radioallergosorbent test (RAST) to the foods suggest involvement of immunoglobulin (Ig)E-anaphylaxis in both disorders. The triggering foods and initial target organs are usually different in each case. In the present study, a 32-year-old male reported dyspnea accompanied by wheals, and symptoms of low blood pressure while walking after eating Chinese noodles and donuts. He also reported uncomfortable sensations in his mouth and throat after ingesting melon. Exercise challenge tests were administered. Serum histamine, plasma adrenaline, noradrenaline and dopamine were measured pre- and post-test. No symptoms were induced by exercise or by the ingestion of any single food item before exercise. However, numerous wheals appeared when exercise followed the combined ingestion of foods. Likewise, the sequence of eating pancakes and then exercising resulted in numerous wheals and anaphylaxis. Olopatadine hydrochloride and ketotifen fumarate completely inhibited this anaphylaxis. The skin prick tests resulted in fruit-induced erythema and wheals. The results of these tests with wheat, butter and sugar were negative, and no symptoms were induced by the exercise test after ingestion of watermelon, melon or apple. The anaphylactoid symptoms were accompanied by a significant increase of plasma noradrenaline. In this case, not only wheat, but sugar and butter may induce the onset of FDEIA. There was no significant correlation between the intensity of the symptoms and the serum histamine levels in the present case. Noradrenaline may be involved in the onset of FDEIA, since noradrenaline may selectively inhibit T-helper (Th)1 functions while favoring Th2 responses. The tests showed no cross-reactivity between the

  13. Mast cell stabilization alleviates acute lung injury after orthotopic autologous liver transplantation in rats by downregulating inflammation.

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    Ailan Zhang

    Full Text Available BACKGROUND: Acute lung injury (ALI is one of the most severe complications after orthotopic liver transplantation. Amplified inflammatory response after transplantation contributes to the process of ALI, but the mechanism underlying inflammation activation is not completely understood. We have demonstrated that mast cell stabilization attenuated inflammation and ALI in a rodent intestine ischemia/reperfusion model. We hypothesized that upregulation of inflammation triggered by mast cell activation may be involve in ALI after liver transplantation. METHODS: Adult male Sprague-Dawley rats received orthotopic autologous liver transplantation (OALT and were executed 4, 8, 16, and 24 h after OALT. The rats were pretreated with the mast cell stabilizers cromolyn sodium or ketotifen 15 min before OALT and executed 8 h after OALT. Lung tissues and arterial blood were collected to evaluate lung injury. β-hexosaminidase and mast cell tryptase levels were assessed to determine the activation of mast cells. Tumor necrosis factor α (TNF-α, interleukin (IL-1β and IL-6 in serum and lung tissue were analyzed by enzyme-linked immunosorbent assay. Nuclear factor-kappa B (NF-κB p65 translocation was assessed by Western blot. RESULTS: The rats that underwent OALT exhibited severe pulmonary damage with a high wet-to-dry ratio, low partial pressure of oxygen, and low precursor surfactant protein C levels, which corresponded to the significant elevation of pro-inflammatory cytokines, β-hexosaminidase, and tryptase levels in serum and lung tissues. The severity of ALI progressed and maximized 8 h after OALT. Mast cell stabilization significantly inhibited the activation of mast cells, downregulated pro-inflammatory cytokine levels and translocation of NF-κB, and attenuated OALT-induced ALI. CONCLUSIONS: Mast cell activation amplified inflammation and played an important role in the process of post-OALT related ALI.

  14. Ophthalmic antihistamines and H1-H4 receptors. (United States)

    Wade, Laurie; Bielory, Leonard; Rudner, Shara


    Antihistamines exert pharmacologic effects by binding to four histamine receptors (H1-H4) at different affinities, producing variable effects depending on the receptor they predominantly bind to. This review's purpose is to determine the relative potency of antihistamines by comparing their binding affinities to these receptors. Studies on binding affinities of antihistamines to histamine receptors were reviewed and the dissociation constant for inhibitor binding (Ki) analyzed to determine the most and least potent antihistamine for each receptor. We retrieved the binding affinities for nineteen antihistamines. For H1 receptors, pyrilamine exhibited the highest affinity (Ki = 0.8 nM), and thioperamide the lowest (Ki = 280, 000 nM). For H2 receptors, ranitidine exhibited the highest affinity (Ki = 187 nM), and olopatadine the lowest (Ki = 100 ,000 nM). For the recently discovered H3 and H4 receptors, thioperamide exhibited the highest affinity (Ki = 1.1 nM), and olopatadine exhibited the lowest (Ki = 79 ,400 nM), to H3. Data on binding affinities to the H4 receptor exist for: ketotifen, pheniramine, ranitidine, cimetidine and thioperamide. Of these, thioperamide exhibited the highest affinity (Ki = 27 nM), whereas cimetidine and ranitidine exhibited the lowest affinity (Ki = >10, 000 nM) for H4 receptors. This review summarizes the relative potency of antihistamines based on their binding affinities to the four histamine receptors. Although data on binding affinities of antihistamines to the H4 receptor are sparse, it is apparent that further research on these histamine subtypes may open new venues for more direct treatment with a higher therapeutic efficacy on allergic disorders including those affecting the ocular surface.

  15. Nifedipine Asma y Nifedipina: estudio comparativo del efecto profiláctivo de la Nifedipina frente al Ketotifeno y placebo en Asma Alérgica Infantil

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    Fernando Montoya


    Full Text Available

    Between July 1984 and December 1986 a double blind randomized study was conducted at the Allergy Clinic of the Hospital Universitario San Vicente de Paúl, Medellín, Colombia, in order to compare the effects of Nifedipine, Ketotifen and placebo on allergic asthma in children; each drug and the placebo were administered orally every 12 hours for a period of 4 months to a group of 20 children. The objective was to evaluate the usefulness of Nifedipine In the prophylactic management of allergic asthma in this population and to compare it with Ketotifen, a provenly efficacious drug, and placebo.


    AII patients were older than 5 years and had suffered the disease for more than 2 years. Nifedipine treated patients showed a reduction In the frequency of their asthmatic crisis (17 patients; 85% and in their intensity and duration (16 patients; 80%; a similar reduction was observed In the need for bronchodilators; 18 patients {90% reported beneficial effects with this drug and medical evaluation confirmed Improvement In 14 {70%.


    These results resembled those obtained with Ketotifen and both were statistically superior to placebo {p<0.05. Pulmonary function tests, pulse rate and blood pressure did not show any significant changes. Secondary effects were minimal and self-Limited.


    It is concluded that Nifedipine can be an alternative drug for the treatment of mild to moderate allergic asthma In children. If calcium antagonists with higher

  16. Comportamiento del asma bronquial en la edad pediátrica

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    Lilian Jiménez Fontao


    Full Text Available Se realizó un estudio observacional, analítico, con un modelo de diseño del tipo casos y controles en la población de niños que acuden al Círculo Infantil "Sueños del Ché", con el fin de determinar la posible influencia de algunos factores de riesgo para padecer de asma bronquial. La investigación se realizó durante el curso escolar 1996-1997. El material de estudio quedó conformado por 166 niños, 21 de los cuales eran asmáticos (GE, el resto (145 eran los supuestamente sanos y conformaron el grupo control (GC. Como instrumento epidemiológico se utilizó el riesgo relativo (RR y su intervalo de confianza al 95 %, así como la prueba de Chi cuadrado. El sexo masculino predominó entre los enfermos y las manifestaciones alérgicas fueron más frecuentes entre los niños enfermos, así como en aquellos cuyos familiares era fumadores o que padecían de asma bronquial. El ketotifeno consiguió el 50 % de mejoría entre los enfermos, y la presencia de vectores y/o animales en el hogar no resultó un factor importante a considerarAn observational analytic case-control study was conducted in the population of children attending the "Sueños del Ché" Day Care Center in order to determine the possible influence of some risk factors on bronchial asthma. The investigation was made during the academic course 1996-1997. 166 children, 21 of whom were asthmatics (SG, and other 145 apparently sound (CG took part in the study. The relative risk and its confidence interval of 95 %, as well as the Chi square test were used as an epidemiological tool. Males prevailed among the sick and the allergic manifestations were more common in ill children and in those whose relatives were smokers or suffered from bronchial asthma. An improvement of 50 % was attained with the admnistration of ketotifen. The presence of vectors and/or animals at home was not an important factor to be considered

  17. In vitro desensitization of beta-adrenoceptors in guinea pig trachea: interactions between beta-adrenoceptor agonists and influence of adenosine and other drugs. (United States)

    Matran, R; Naline, E; Advenier, C; Duroux, P


    The aim of this study was to investigate quantitatively the action of and the interaction between beta-adrenergic receptor agonists in desensitizing guinea pig isolated trachea. It was also to evaluate the influence of substances whose effects on desensitization are either disputed (theophylline, indomethacin, ketotifen, hydrocortisone) or unknown (nicardipine, Bay K 8644, fenspiride, adenosine). Tracheal strips were contracted with histamine (5 x 10(-5) M) or acetylcholine (5.10(-5) M) and concentration-response (C/R) curves for various beta-adrenoceptor agonists were determined before and after incubation (20 min to 4 h) with the same beta-adrenoceptor agonist (autodesensitization), with other beta-adrenoceptor agonists (cross-desensitization), or with a beta-adrenoceptor agonist and another substance. Our results show that the autodesensitization induced by isoprenaline is concentration dependent and that concentration dependence is more pronounced with salbutamol and fenoterol than with isoprenaline and adrenaline with respect to autodesensitization: shifts (log unit) of the C/R curves were 0.59 +/- 0.06 (N = 5) for salbutamol (10(-5) M), 0.78 +/- 0.09 (N = 5) for fenoterol (10(-6) M), 0.30 +/- 0.04 (N = 9) for isoprenaline (10(-5) M), and 0.33 +/- 0.05 (N = 5) for adrenaline (10(-5) M). Our studies of cross-desensitization (desensitization to isoprenaline, adrenaline, salbutamol, and fenoterol induced by incubation with isoprenaline 10(-5) M) showed a significantly greater shift in the C/R curves for fenoterol (0.56 +/- 0.08, N = 5) and salbutamol (0.62 +/- 0.05, N = 5) than for adrenaline (0.35 +/- 0.07, N = 5) and isoprenaline itself (0.30 +/- 0.05, N = 9). Of the substances we studied, none modified the desensitization induced by isoprenaline except hydrocortisone and adenosine. Hydrocortisone (10(-8) M) reduced it significantly, although to a negligible extent. Adenosine (3 x 10(-4) M) did not shift the C/R curve to isoprenaline by itself, but incubation

  18. Cuantificación de glibenclamida en muestras de limpieza de equipos farmacéuticos mediante cromatografía líquida de alta resolución Quantification of glibenclamide in cleaning samples of pharmaceutical equipment through high performance liquid chromatography

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    Alen Nils Baeza Fonte


    ; with 0.037 mol/L concentration pH 5.25 and flow of 1.5 mL/min, in a Nucleosil 100 C8 column. Glibenclamide was injected with progesterone as internal standard and using an UV detector= 230 nm Results: the method was linear in the 0.4-150 mg/mL concentration interval having a detection and quantization limits of 10 and 40 ng/mL respectively. It was specific to analyte when placebo is present, to degradation products and to other active ingredients. Possible interferences with the proposed method was considered for captopril, chlortalidone, dexametasone, diphenhydramin HCl, digoxine, 8-chlortheophylline, diphenhydramina HCl, phenobarbital, haloperidol, hydrochlorothiazide, fumaric acid, ketotifen, metoclopramide HCl, piridoxine HCl, piroxicam, prednisone and nifedipine, On the other hand, ibuprofen, indometacin, trifluoperazine HCl, thioridazine HCl and imipramine were identified as interferences in the procedure at concentration figures close to 10 mg/mL. Conclusions: the present method is sensitive, quick and selective for the evaluation of residues of active pharmaceutical principle glibenclamide in tablet production equipment after a swap sampling and it could be potentially used in case of cross-contamination of glibenclamide and other drugs already described.