Effect of ketotifen fumarate on experimental autoimmune orchitis and torsion of the spermatic cord / 亚洲男科学杂志(英文版)

The aim of this work was to study effects of ketotifen fumarate (KF) on prevention of tissue damage in testes of rats with experimental autoimmune orchitis (EAO) and on the contralateral testis in a model of prolonged testicular cord torsion (TCT). Rats with EAO or TCT were injected intraperitoneally once daily with KF or saline solution (vehicle group). Incidence and severity of testicular damage were evaluated by histopathology using an EAO score or a Johnsen score. Mast cells (MC) were identified by histochemistry and quantified. In EAO model, KF significantly reduced severity of histopathological testicular damage compared to rats in the vehicle group. KF also reduced the number of testicular MC compared to vehicle group. Similarly, in TCT model, multifocal damage of the contralateral testis was observed 30 days after testicular torsion characterized by sloughing of the germinal epithelium, seminiferous tubule atrophy, and interstitial edema. Focal signs of inflammation and fibrosis of seminiferous tubular walls were also observed. In contrast, sections of contralateral testis of rats injected with KF and killed 30 days after surgery showed normal histological features. A significant decrease in the number of MC was observed in rats treated with KF compared to untreated animals. In conclusion, we demonstrated that treatment with KF reduced testicular inflammatory process and MC infiltrates in both EAO and TCT models. The results suggest a promising treatment for infertile male patients with testicular pathologies associated with inflammation and germ cell loss.

Effect of ketotifen fumarate on experimental autoimmune orchitis and torsion of the spermatic cord / 亚洲男科学杂志(英文版)

The aim of this work was to study effects of ketotifen fumarate (KF) on prevention of tissue damage in testes of rats with experimental autoimmune orchitis (EAO) and on the contralateral testis in a model of prolonged testicular cord torsion (TCT). Rats with EAO or TCT were injected intraperitoneally once daily with KF or saline solution (vehicle group). Incidence and severity of testicular damage were evaluated by histopathology using an EAO score or a Johnsen score. Mast cells (MC) were identified by histochemistry and quantified. In EAO model, KF significantly reduced severity of histopathological testicular damage compared to rats in the vehicle group. KF also reduced the number of testicular MC compared to vehicle group. Similarly, in TCT model, multifocal damage of the contralateral testis was observed 30 days after testicular torsion characterized by sloughing of the germinal epithelium, seminiferous tubule atrophy, and interstitial edema. Focal signs of inflammation and fibrosis of seminiferous tubular walls were also observed. In contrast, sections of contralateral testis of rats injected with KF and killed 30 days after surgery showed normal histological features. A significant decrease in the number of MC was observed in rats treated with KF compared to untreated animals. In conclusion, we demonstrated that treatment with KF reduced testicular inflammatory process and MC infiltrates in both EAO and TCT models. The results suggest a promising treatment for infertile male patients with testicular pathologies associated with inflammation and germ cell loss.

Comparison of the efficacy of montelukast or ketotifen combined with salmeterol/fluticasone in the treatment of cough variant asthma / 中国基层医药

Objective To compare the efficacy of montelukast or ketotifen combined with salmeterol/fluticasone powder inhalation in the treatment of cough variant asthma.Methods From July 2016 to July 2017,74 patients with cough-variant asthma admitted to the 903rd Hospital of People's Liberation Army Joint Service Support Unit were selected.According to the random number table method,the patients were randomly divided into the control group and observation group,with 37 patients in each group.All patients were treated with inhalation of salmeterol/fluticasone,with montelukast chewable tablets in the observation group,and ketotifen tablets in the control group.The adverse reactions in the two groups after treatment were recorded,and the treatment effect and typical asthma conversion rate in the two groups were compared.Results The total effective rate of the observation group was 94.59％,which was significantly higher than 78.38％ of the control group (x2 =8.283,P ＜ 0.05).The incidence rate of adverse reactions was 10.81％ in the observation group and 16.22％ in the control group,there was no statistically significant difference between the two groups (x2 =2.082,P ＞ 0.05).In the observation group,2 patients had nausea,and 2 patients had laryngopharyngeal discomfort.In the control group,1 patient had laryngopharyngeal discomfort,2 patients had dizziness,and 3 patients had somnolence.All the above symptoms were mild and could be relieved after symptomatic treatment.After 1 year of follow-up,the recurrence rate of the observation group was 27.03％,which was significantly lower than 43.24％ of the control group (x2 =8.072,P ＜ 0.05).After 1 year of follow-up,the typical asthma conversion rate of the observation group was 21.62％,which was significantly lower than 37.84％ of the control group (x2 =7.322,P ＜ 0.05).Conclusion Montelukast in the treatment of cough variant asthma can greatly reduce the recurrence rate and the conversion rate of typical asthma.It is not only safe but also effective.It is worthy of popularizing in clinic.

Comparison of the efficacy of montelukast or ketotifen combined with salmeterol/fluticasone in the treatment of cough variant asthma / 中国基层医药

Objective@#To compare the efficacy of montelukast or ketotifen combined with salmeterol/fluticasone powder inhalation in the treatment of cough variant asthma.@*Methods@#From July 2016 to July 2017, 74 patients with cough-variant asthma admitted to the 903rd Hospital of People's Liberation Army Joint Service Support Unit were selected.According to the random number table method, the patients were randomly divided into the control group and observation group, with 37 patients in each group.All patients were treated with inhalation of salmeterol/fluticasone, with montelukast chewable tablets in the observation group, and ketotifen tablets in the control group.The adverse reactions in the two groups after treatment were recorded, and the treatment effect and typical asthma conversion rate in the two groups were compared.@*Results@#The total effective rate of the observation group was 94.59%, which was significantly higher than 78.38% of the control group (χ2=8.283, P<0.05). The incidence rate of adverse reactions was 10.81% in the observation group and 16.22% in the control group, there was no statistically significant difference between the two groups (χ2=2.082, P>0.05). In the observation group, 2 patients had nausea, and 2 patients had laryngopharyngeal discomfort.In the control group, 1 patient had laryngopharyngeal discomfort, 2 patients had dizziness, and 3 patients had somnolence.All the above symptoms were mild and could be relieved after symptomatic treatment.After 1 year of follow-up, the recurrence rate of the observation group was 27.03%, which was significantly lower than 43.24% of the control group (χ2=8.072, P<0.05). After 1 year of follow-up, the typical asthma conversion rate of the observation group was 21.62%, which was significantly lower than 37.84% of the control group (χ2=7.322, P<0.05).@*Conclusion@#Montelukast in the treatment of cough variant asthma can greatly reduce the recurrence rate and the conversion rate of typical asthma.It is not only safe but also effective.It is worthy of popularizing in clinic.

Protective effect of MUC2 in mice with colitis and the expression of anti-CBir1 antibody in serum / 中国病理生理杂志

AIM:To investigate the protective effect of mucin 2(MUC2)on intestinal mucosa of colitis model mice,and to explore the correlation between the expression of anti-CBir1 flagellin antibody and MUC2.METHODS:The mice were randomly divided into normal control group,2,4,6-trinitrobenzenesulfonic acid(TNBS)group,lipopolysaccha-ride(LPS)+ovalalbumin(OVA)+TNBS group and ketotifen+TNBS group.The expression of MUC2 in colon tissue was determined by PAS staining and immunohistochemistry, and the anti-CBir1 antibody level in the serum of mice in each group was measured by ELISA.RESULTS:The scores of disease activity index and histological index in TNBS group were higher than those in normal control group(P<0.05).The scores in LPS +OVA+TNBS group were much higher than those in TNBS group(P<0.05).However, the values in ketotifen +TNBS group were lower than those in TNBS group (P<0.05).PAS staining showed a decrease in goblet cells in TNBS group.Compared with TNBS group,the colonic mu-cosa integrity in LPS+OVA+TNBS group was destroyed, and the number of goblet cells in ketotifen +TNBS group in-creased significantly.Immunohistochemical staining showed that the expression of MUC 2 in the intestinal tract of each mo-del group was basically consistent with the results of PAS staining.The serum anti-CBir1 antibody level in TNBS group was higher than that in normal control group(P<0.05), and that in LPS+OVA+TNBS group was significantly higher than that in TNBS group(P<0.05),whereas that in ketotifen +TNBS group was decreased slightly(P<0.05).CONCLU-SION:MUC2 plays a protective role in the pathogenesis of colitis in mice,and there is a negative correlation between the expression of MUC2 and the bacterial flagellin in the intestinal mucosa of mice with colitis.

Comparison of clinical effect of montelukast and ketotifen in the treatment of children with cough variant asthma / 中国基层医药

Objective To compare the clinical effect of montelukast sodium and ketotifen in the treatment of children with cough variant asthma,thus to provide theoretical basis for clinical treatment.Methods 61 children with cough variant asthma were randomly divided into control group and observation group according to the digital table method,31 cases in each group.Patients of two groups were all given antispasmodic and antitussive.The control group was given ketotifen tablets drug therapy,1mg/time,2 times/d,and the observation group was treated with montelukast chewable tablets,5mg/time,1 time /d.After 8 weeks of treatment,the clinical effects were compared between the two groups.Results The total effective rate of the observation group (96.77%)was higher than that of the control group (77.42%),and the difference was statistically significant (χ2 =16.65,P <0.05).The clinical symptoms improved time of the observation group was (5.78 ±1.36)d,which was shorter than (8.45 ±2.24)d of the control group,the difference was statistically significant (t =2.71,P <0.05).The recurrence rate of the observation group (6.45%) was lower than the control group (16.13%),the difference was statistically significant (χ2 =4.67,P <0.05 ). Recurrence time of the observation group was better than that of the control group,the difference was statistically significant (t =7.98,P <0.05 ).Conclusion The curative effect of montelukast special chewing tablets in the treatment of children with bronchial asthma is obviously superior to ketotifen,has less adverse reactions.It was worthy of clinical application.

Bubbly orange baby: A rare case of diffuse cutaneous mastocytosis, bullous type

Mastocytosis is an uncommon, sporadic, heterogenous illness resulting from hyperplasia of mast cells. Diffuse cutaneous mastocytosis is the rarest subtype of mastocytosis affecting children, with bullous mastocytosis being its least common variety. Systemic manifestations like nausea, vomiting, bone pain, diarrhea, and central nervous system abnormalities are less common in children than adults. We report a four-month old male who presented with a two-month history of generalized yellowish to tan macules, papules and plaques with peau d'orange texture, with some blisters and erosions on the back, abdomen and scalp. Darier's sign was positive. Baseline laboratory workup were negative for systemic involvement. CD117 and Giemsa staining were positive for mast cells. Based on the clinical findings and histopathologic results, a diagnosis of bullous mastocytosis was made. Treatment included ketotifen drops, mupirocin cream and cetirizine drops, which resulted in flattening of most lesions and resolution of blisters and erosions.

Novel Suppressive Effects of Ketotifen on Migration and Invasion of MDA-MB-231 and HT-1080 Cancer Cells

The high mortality rates associated with cancer reflect the metastatic spread of tumor cells from the site of their origin. Metastasis, in fact, is the cause of 90% of cancer deaths. Therefore, considerable effort is being made to inhibit metastasis. In the present study, we screened ketotifen for anti-migratory and anti-invasive activities against MDA-MB-231 breast cancer and HT-1080 fibrosarcoma cancer cells. Cancer cell migration and invasion were measured using multi-well chambers. Additionally, western blots were used to examine the effects of ketotifen on the expressions of CDC42, Rho, Rac, and matrix metalloproteinase 9 (MMP-9). The results showed that ketotifen dose-dependently suppressed the migration and invasion of MDA-MB-231 and HT-1080 cells. Ketotifen also suppressed the expressions of CDC42, Rac, and Rho, which, significantly, are involved in MDA-MB-231 and HT-1080 cancer cell migration. Moreover, ketotifen suppressed the expression and activity of MMP-9, which is involved in degradation of the extracellular matrix leading to invasion. The overall data suggested that ketotifen suppresses the migration and invasion of MDA-MB-231 and HT-1080 cancer cells via inhibition of CDC42, Rac, Rho, and MMP-9 expression.

Evaluation of the Stabilization of Human Umbilical Cord Blood-Derived Mast Cells in Accordance with Ketotifen and Olopatadine Concentration

PURPOSE: To evaluate the effect of olopatadine and ketotifen to stabilize mast cells using human umbilical cord blood-derived mast cells (hCBMCs). METHODS: Using cultured hCBMCs, we divided the cells into the Ketotifen fumarate treatment group, the Olopatadine hydrochloride treatment group, the positive control group, and the negative control group. The histamine release inhibition rate was then observed. RESULTS: Ketotifen and olopatadine both showed the highest inhibition rate of histamine release at a concentration of 10(-3.5)M (Ketotifen, 48% and Olopatadine, 62%). The histamine release inhibition rate of olopatadine was 28% at a concentration of 10(-5.5)M, but ketotifen demonstrated a low histamine release inhibition rate at the same concentration. Ketotifen and olopatadine showed no histamine release inhibition at concentrations of 10(-2)~10(-2.5)M, and 10(-6)M. CONCLUSIONS: Ketotifen and olopatadine demonstrated histamine inhibition in the concentration range of 10(-3) to 10(-5)M. Olopatadine showed a slightly stronger response than ketotifen in the inhibition of histamine release.

In vitro study on the interaction of ketotifen fumarate with anhydrous theophylline

The purpose of the present study was to investigate the interaction between ketotifen fumarate and anhydrous theophylline in aqueous media of various pH (1.2 and 6.8). Using Job's continuous-variation analysis and Ardon's spectrophotomeric measurement methods, the values of the stability constants of theophylline with ketotifen were determined at a fixed temperature (37 ºC) at various pH. The stability constants, ranging between 5.66 and 9.92, were derived from Ardon's plot, indicating that comparatively stable complexes had formed as a result of an interaction between the drugs. However, following the interaction of theophylline with ketotifen, stability constants were <1 at gastric pH (1.2) and intestinal pH (6.8). Concurrent administration of ketotifen and theophylline could result in the formation of a stable complex and this is likely to reduce the therapeutic activities of both drugs.

O objetivo do presente estudo foi investigar a interação entre o fumarato de cetotifeno e a teofilina anidra em meios aquosos com vários pH (1,2 e 6,8). Utilizando a análise da variação contínua de Job e os métodos de medida espectrofotométrica de Ardon, os valores das constantes de estabilidade da teofilina com o cetotifeno foram determinados em temperatura fixa (37 oC) em vários pH. As constantes de estabilidade, variando entre 5,66 e 9,92 derivaram-se a partir do delineamento de Ardon, indicando, comparativamente, que complexos estáveis se formaram como resultado da interação entre os fármacos. Entretanto, seguindo a interação da teofilina com o cetotifeno, as constantes de estabilidade foram <1, em pH gástrico (1,2) e intestinal (8,8). A administração concomitante de cetotifeno e teofilina poderia resultar na formação de complexo estável, o que reduz a atividade terapêutica de ambos os fármacos.

Cost effectiveness analysis of five different treatment alternatives in seasonal allergic conjunctivitis.

Seasonal allergic conjunctivitis is an illness which decreases quality of life and is common in society. Pharmacoeconomic evaluation about seasonal alergic conjunctivitis has not been measured in Turkey. The aim of our study is to understand the cost-effective medicines which are used for seasonal allergic conjunctivitis with Turkish data. In our study, effectiveness data from randomized controlled trials done with fluorometholon, epinastin, olopatadin, emedastin and ketotifen were used. Different effectiveness data reported in the trials were reduced to one single dataset. For cost data, direct costs like drug cost and physician meetings were counted in the calculation. Incremental cost effectiveness analysis (ICER) was performed with effectiveness and cost data which were obtained. In cost analysis lowest treatment cost was established by fluorometholon (US$ 38.94) and followed by ketotifen (US$ 43.41),epinastine (US$ 43.60), olopatadine (US$ 44.05) and emedastine (US$ 44.92), respectively. When the drugs compared for incremental cost-effectiveness, emedastine was dominated by ketotifen and emedastine dominated by olopatadine; ketofien could be compared with fluorometholon and olopatadine. Turkish data obtained and analyzed were similar with the literature. Reimburstment foundations can feature preparations which contain olopatadin and epinastin in treatment protocols, in the light of obtained data.

Diseño de una formulación de ketotifeno 0, 025 por ciento colirio / Design of a Ketotifen formula: 0, 025 percent eyedrops

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 por ciento, 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 ademàs, 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 ambiente.

The 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 percent 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.

Periorbital Allergic Contact Dermatitis to Ketotifen Fumarate Eyedrops / 대한피부과학회지

Ketotifen fumarate (KF) is a widely used drug for prophylaxis and the treatment of allergic conditions. Adverse cutaneous reactions to KF are rare except for dryness of the skin and mouth. To the best of our knowledge, no case of allergic contact dermatitis to ketotifen fumarate has yet been reported in the Korean literature. A 60-year-old woman presented with pruritic erythematous patches on the periorbital area. She had used KF eyedrops (Ketoftil ophthalmic solution(R)) for itchy eyes after cataract surgery, and the periorbital lesions developed four weeks later. The KF eyedrops contained not only KF (0.69 mg/ml) but also benzalkonium chloride (0.1 mg/ml). We performed patch tests with the Korean standard patch test series:KF (0.69 mg/ml, 0.069 mg/ml and 0.0069 mg/ml in aqueous solution), and benzalkonium chloride (0.1% in petrolatum). These patch tests showed weak positive reaction to KF (0.69 mg/ml and 0.069 mg/ml) and nickel sulfate, and a negative reaction to benzalkonium chloride. The skin lesions improved rapidly after stopping the eyedrops and applying a topical steroid. We herein report on a rare case of allergic contact dermatitis to ketotifen fumarate eyedrops.

Wheat-dependent, Exercise-induced Anaphylaxis: A Successful Case of Prevention with Ketotifen

Food-dependent, exercise-induced anaphylaxis (FDEIA) is the triggering of anaphylaxis after ingestion of certain foods when followed by physical exercise. Symptoms vary from the typical generalized urticaria to severe allergic reactions. We report the case of a 20-year-old woman who had a 7-year history of recurrent wheals and dyspnea after ingesting several kinds of food (wheat, pork, and beef) along with physical exercise. Based on a provocation test, she was diagnosed with wheat-dependent, exercise-induced anaphylaxis. She was instructed to take 2 mg of ketotifen 2 hours before ingestion of wheat to prevent the symptoms, and subsequently the provocation test did not elicit wheals. We therefore prescribed ketotifen (1 mg twice a day). She has not had recurrent wheals or dyspnea for 6 months. We herein report an interesting case of wheat-dependent, exercise-induced anaphylaxis with successful prevention by ketotifen.

Effects of Ketotifen on an Experimental Model of IgA Nephropathy

PURPOSE: The intestinal mucosal defect has been known as one of the pathogenicmechanisms of IgA nephropathy. Oral antigens usually induce the activation of Th2 cells and mast cells. These cells secrete cytokines IL-4, IL-5 and TGF-beta, which increase IgA production. Although ketotifen (benzocycloheptathiophene) is an H1 antagonist and a mast cell membrane stabilizer, it could protect the gastrointestinal membrane through inhibiting the production of IL-4, IL-5, PGE2, and LTB4, and decreasing the activity of nitric oxide synthease. Therefore, we have investigated if ketotifen may protect the development of IgA nephropathy with an oral antigen. METHODS: ICR mice were used as an animal model orally with Poliovax only [ketotifen (-)], the other group was given oral ketotifen [ketotifen (+)] in addition to Poliovax. RESULTS: Mesangial IgA deposition developed in 11 out of the 18 mice in the ketotifen (-) group, while in three out of the nine mice in ketotifen (+) group. The mesangial change developed in 16 out of the 18 mice in the ketotifen (-) group, while in five out of the nine mice in the ketotifen (+) group. Serum IL-4 and IL-5 levels were not significantly lower in the latter group than in the former. CONCLUSION: According to the statistical results from the above, ketotifen therapy would be beneficial to reducing mesangial changes in IgA nephropathy.

Comparação entre o uso tópico do fumarato de cetotifeno 0.025 por cento e do cloridrato de olopatadina 0.1 por cento no tratamento da ceratoconjuntivite primaveril / Comparative study between 0.025 percent ketotifen fumarate and 0.1 percent olopatadine hydrochloride in the treatment of vernal keratoconjunctivitis

OBJETIVO: O objetivo desse estudo foi comparar as soluções oftálmicas de fumarato de cetotifeno 0,025 por cento e de cloridrato de olopatadina 0,1 por cento em pacientes portadores de ceratoconjuntivite primaveril. MÉTODOS: Avaliação realizada em um único centro, simples-cega, comparando-se paralelamente cetotifeno e olopatadina. As medicações foram avaliadas em 4 momentos (dias 1, 7, 14 e 21) por meio de tabelas de graduações padronizadas. A freqüência de eventos adversos foi a principal variável de segurança. RESULTADOS: Na avaliação da evolução do prurido ocular, ardor, lacrimejamento, hiperemia conjuntival, secreção e fotofobia observou-se que o uso tópico do cetotifeno proporcionou melhora significante deste sintoma em relação a olopatadina (p>0,05). Observou-se que a partir do 7° dia de tratamento os pacientes em uso da olopatadina tinham menos ardor, em relação aos que fizeram uso do cetotifeno, mas após o 21° dia essa relação inverteu. Na comparação da sensação de corpo estranho, papilas e pontos de Horner-Trantas evidenciou-se equivalência sem significância estatística. CONCLUSÃO: Concluímos que ambas são drogas equivalentes e atuaram de forma eficaz e segura na remissão dos sintomas relacionados à conjuntivite alérgica primaveril. Houve diferença a favor do cetotifeno (p<0,05) na melhora do prurido, lacrimejamento, hiperemia conjuntival, presença de secreção e fotofobia.

PURPOSE: To compare the topical use of 0.025 percent ketotifen fumarate and 0.1 percent olopatadine hydrochloride in the treatment of patients with vernal keratoconjunctivitis. METHODS: A study performed in one center, simple masked, parallel-group compared ketotifen and olopatadine. These patients were evaluated on four visits during the treatment (days 1, 7, 14 and 21), defined by ratings scores. Adverse events were the main variable of safety rating. RESULTS: On evaluating ocular itching, burning, tearing, conjunctival hyperemia, mucous discharge and photophobia, the ketotifen group showed a significant improvement of total signs and symptoms (p<0.05). Between the baseline and the 2nd visit, treatment with olopatadine resulted in decreased burning, but after the 4th visit, ketotifen was slightly better. Sand sensation, papillae and Horner-Trantas dots were not significantly different in both groups. CONCLUSION: Both drugs were efficient and safe relieving the main symptoms and signs of vernal keratoconjunctivitis. Between the same timepoints, there was a significant difference in favor of ketotifen-treated patients (p<0.05), showing improvement of itching, tearing, conjunctival hyperemia, mucous discharge and photophobia.

Inhibitory Effect of Disosium Cromoglycate and Ketotifen on Human Seminal Plasma-Induced Mast Cell Activation

BACKGROUND: Human seminal plasma (HSP)-induced hypersensitivity is one of the serious complications with sexual intercourse. The clinical manifestations of HSP-induced hypersensitivity may be related to the release of vasoactive mediators from mast cell induced by HSP. It has recently been reported that HSP modulates immune systems and induces mast cell degranulation and histamine release from rat peritoneal mast cells (RPMC). Ketotifen and disodium cromoglycate (DSCG), anti-asthmatic and anti-allergic drugs, have a role of mast cell stabilization and inhibit mast cell-induced leukocyte rolling and adhesion. But the inhibitory agents of HSP-induced mast cell activation are unknown. This study was performed to investigate the effects of DSCG and ketotifen on the HSP-induced mast cell activation. METHODS: For this, influences of DSCG and ketotifen on the human seminal plasma-induced degranulation, histamine release and morphological changes of RPMC were observed. RESULTS: The mast cell degranulation and histamine release of RPMC by HSP were induced in a dose-dependent fashion. The HSP-induced cytomorphological changes such as swelling, intracellular vacoules, and interrupted cell boundary were significantly inhibited by pretreatment with DSCG or ketotifen. DSCG and Ketotifen inhibited the HSP-induced degranulation and histamine release from RPMC. CONCLUSION: From the above results, it is suggested that DSCG and ketotifen have a inhibitory effect of the HSP-induced mast cell activation. DSCG and ketotifen may be used for treatment of HSP-induced hypersensitivity.

Treatment of experimental allergic conjunctivitis with compound ketotifen eye drops / 中华实验眼科杂志

Objective:To examine the effect of compound ketotifen eye drops(CKF,containing 0.1% ketotifen and 0.000 5% dexamethasone) on experimental acute allergic conjunctivitis in rats.Methods:27 male Wistar rats were immunized by intraperitoneal injection of egg albumin and were randomized into three groups: CKF,0.1% ketotifen (KF) and 0.000 5% dexamethasone (DM) Rats in each group received the respective eye drops in one eye and vehicle in the other eye 60,45,30,15 min before and 15,30 min after challenge.Immediately before challenge,the rats were injected intravenously with Evans Blue(EB).The challenge was performed by topical instillation of egg albumin,and 60 min later,the animals were killed and the dye was extracted from the eyes.The intensity of EB extravasation was determined by spectrophotometry at 620nm and inhibitory rates were calculated.Results:CKF,KF and DM suppressed EB extravasation significantly.The inhibitory rate was 53.98%±15.57% for CKF,27.91%±28.36% for KF and 11.90%±34.16% for DM.CKF was more effective than both KF and DM on inhibiting dye vascular leakage in the eyes (P＝0.028,0.004,respectively).Conclusion:These data clearly indicate that the compound of ketotifen eye drops has potential as a topical ocular formulation for anti-allergic disease.

In vitro Potentiation of Chloroquine Activity in Plasmodium falciparum by Ketotifen and Cyproheptadine / 中国寄生虫学与寄生虫病杂志

Objective To study the potentiation of chloroquine activity and mechanism by ketotifen and cyproheptadine in in vitro cultured Plasmodium falciparum Fcc SM1/yN strain. Methods In vitro cultured Fcc SM1/yN strain was added to pre-prepared drug plates at 50 ?l/well after synchronization to make final concentration of 0.312 5-2 560 nmol/L for chloroqine and of 9.80-5 000 nmol/L for ketotifen or cyproheptadine. After 34 hours' culture in 37 ℃, the number of schizonts with 3 or more nuclei was calculated among 200 parasites under microscope. Calculated half inhibitive concentration ( IC50 ) of chloroquine and every drug combination to parasite as well as chloroquine activity enhancement index ( AEI) of ketotifen (or cyproheptadin) . Time dependency of potentiation was studied. All data were analyzed statistically with SPSS 13.0. After 20 hours' action of one optimal combination dose of chloroquine/ketotifen or chloroquine/cyproheptadine, RNA of the Fcc SM1/yN strain was extracted and real-time PCR was used to determine the expression level of pfcrt and pfmdr1 genes. Results The best potentiation effect was observed with ketotifen or cyproheptadine of 625 nmol/L, with IC50 of 74.53 nmol/L for chloroquine/ketotifen and 89.7 nmol/L for chloroquine/cyproheptadine respectively, and activity enhancement index (AEI) of 0.42 for chloroquine/ketotifen and 0.30 for chloroquine/cyproheptadine respectively. Combination of 625 nmol/Lketotifen or cyproheptadine with 5 nmol/L chloroquine showed the highest potentiation potency. 6-7 hours during which ketotifen or cyproheptadine was added after chloroquine showed the highest effect, with IC50 of 67.70 nmol/L for chloroquine/ketotifen and 81.53 nmol/L for chloroquine/cyproheptadine respectively, and the AEI was 0.47 for chloroquine/ketotifen and 0.37 for chloroquine/cyproheptadine respectively. After action of chloroquine/ketotifen or chloroquine/ cyproheptadine at one optimal combination dose, expression level of pfcrt gene increased by 91% and that of pfmdr1 gene decreased by 14% respectively. Conclusion Appropriate combination of chloroquine/ketotiphen or chloroquine/ cyproheptadine potentiates chloroquine against in vitro cultured P. falciparum. 6-7 hour period is an optimal time when ketotifen or cyproheptadine was added after chloroquine. Potentiating activity of ketotifen and cyproheptadine may be related to the expression level of pfcr t and pfmdr1 genes.

Clincal Effect of Ketotifen in Allergic Rhinitis / 영남의대학술지

Ketotifen, a benzocycloheptathiophene, has an orally effective antiallergic as well as antihistaminic properties. In pervious studies, Ketotifen has shown encouraging results on patient with allergic rhinitis, either perennial or seasonal. 39 patients with allergic rhinitis had been treated with Ketotifen 1 mg twice daily for 8 weeks. And we obtained following results. 1) The efficacy rate in sneezing attack was 73.5%, in nasal discharge 71%, in nasal obstruction 58%. 2) Some improvements in at least one of three-major symptoms were noted within 1 week in 30.7%, within 2 weeks in 55.8%, within 3 weeks in 66.7%, within 8 weeks in 87.2%. 3) Physical findings such as colour, swelling of turbinate, character of rhinorrhea were not improved significantly. 4) Side effect was observed only in one patient with abdominal pain and diarrhea, which was subsided after interruption of administration. These results suggested that Ketotifen was effective in treatment of allergic rhinitis.