OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST 36) on duodenal mast cells, nerve growth factor (NGF) and neurotrophic tyrosine kinase receptor type 1 (NTRK1), and to explore the mechanism of electroacupuncture at Zusanli (ST 36) on functional dyspepsia (FD). METHODS: Sixty SPF-grade 10-day-old SD rats were randomly divided into a normal group, a model group, a ketotifen group and an EA group, 15 rats in each group. The FD model was prepared by iodoacetamide combined with rat tail clamping method in the model group, the ketotifen group and the EA group. The rats in the ketotifen group were injected intraperitoneally with ketotifen (1 mg•kg^-1•d^-1) for 7 days; the rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36), with disperse-dense wave, frequency of 2 Hz/50 Hz and intensity of 0.5 mA, 20 min each time, once a day for 14 days. The gastric emptying rate and small intestinal propulsion rate in each group were observed; the morphology of duodenal mucosa was observed by HE staining; the toluidine blue staining was used to observe the number and degranulation of mast cells in duodenal mucosa; the protein and mRNA expressions of NGF, NTRK1 in duodenum were detected by Western blot and real-time PCR; the level of interleukin-1β (IL-1β) in duodenum was measured by ELISA. RESULTS: Compared with the normal group, the gastric emptying rate and small intestinal propulsion rate in the model group were decreased (P<0.01); compared with the model group, the gastric emptying rate and small intestinal propulsion rate in the ketotifen group and the EA group were increased (P<0.01); the small intestinal propulsion rate in the EA group was higher than that in the ketotifen group (P<0.01). In the model group, local defects in duodenal mucosa were observed with a small amount of inflammatory cell infiltration; no obvious abnormality was found in duodenal mucosa of the other groups. Compared with the normal group, the mast cells of duodenal mucosa in the model group were increased significantly with significant degranulation; compared with the model group, the mast cells of duodenal mucosa in the ketotifen group and the EA group were decreased significantly, and the degranulation was not obvious. Compared with the normal group, the protein and mRNA expressions of NGF, NTRK1 as well as the level of IL-1β in duodenum in the model group were increased (P<0.01); compared with the model group, the protein and mRNA expressions of NGF, NTRK1 as well as the levels of IL-1β in duodenum in the ketotifen group and the EA group were decreased (P<0.01, P<0.05); compared with the ketotifen group, the mRNA expression of NGF, as well as the protein and mRNA expressions of NTRK1 in duodenum in the EA group were decreased (P<0.05, P<0.01). CONCLUSION EA at "Zusanli" (ST 36) could inhibit the activation of duodenal mast cells and regulate the expressions of NGF and its receptor to improve the low-grade inflammatory response of duodenum, resulting in treatment effect on FD.
Acupuncture Points ; Animals ; Duodenum/metabolism* ; Dyspepsia/therapy* ; Electroacupuncture ; Ketotifen ; Mast Cells/metabolism* ; Nerve Growth Factor/metabolism* ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Receptor, trkA/genetics*

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.
Animals ; Autoimmune Diseases/pathology* ; Cell Count ; Epididymis/pathology* ; Epididymitis/pathology* ; Histamine H1 Antagonists/pharmacology* ; Hypersensitivity, Delayed ; Immunity, Cellular/drug effects* ; Ketotifen/pharmacology* ; Male ; Mast Cells/pathology* ; Orchitis/pathology* ; Rats ; Severity of Illness Index ; Spermatic Cord Torsion/pathology* ; Testis/pathology* ; Vaccination

Although rare, antihistamines can cause adverse effects, including drug-induced eruptions or anaphylaxis. A 4-year-old child visited the pediatric department of a hospital for skin eruptions after administration of antihistamines, (e.g., ucerax [hydroxyzine] or leptizine [levocetirizine]), for cholinergic rashes; he did not have pruritus. Skin prick, intradermal, and drug provocation tests were performed to determine the relationship between the antihistamines and eruptions. Levocetirizine induced wheals in the skin prick test and a rash in the oral drug provocation test. In contrast, ketotifen induced no reaction in the skin prick test but showed a positive reaction in the oral provocation test. Our case report highlights that children can experience the same types of adverse reactions as seen in adults, and cross-reactivity between various antihistamines can occur.
Adult ; Anaphylaxis ; Child ; Child, Preschool ; Drug Eruptions ; Exanthema ; Histamine Antagonists ; Humans ; Ketotifen ; Pruritus ; Skin ; Urticaria

OBJECTIVE: To study the clinical effect of different combinations of fluticasone propionate (Flu), montelukast sodium (Mon) and ketotifen (Ket) in the treatment of children with cough variant asthma (CVA). METHODS: A total of 280 children with CVA who were admitted to the department of respiratory medicine from June 2015 to January 2018 were randomly divided into Flu+Mon+Ket, Flu+Mon, Flu+Ket, Mon+Ket, Flu, Mon and Ket groups, with 40 children in each group. The children in each group were given corresponding drug(s), and the course of treatment was 3 months for all groups. The condition of cough, cough symptom score, pulmonary function and adverse drug reactions were evaluated after 2 and 3 months of treatment. The children were followed up to observe recurrence. RESULTS: After treatment, cough symptom score tended to decrease in all 7 groups, with increases in percentage of forced expiratory volume in 1 second (FEV1%) and percentage of predicted peak expiratory flow (PEF%). After 2 months of treatment, the Flu+Mon+Ket group had a significantly lower cough symptom score and significantly higher FEV1% and PEF% than the other groups (P<0.05). After 2 and 3 months of treatment, the Ket group had a significantly higher cough symptom score and significantly lower FEV1% and PEF% than the other groups (P<0.05). After 3 months of treatment, there were no significant differences in cough symptom score, FEV1% and PEF% among the other groups (P>0.05). There was a low incidence rate of adverse events in all 7 groups, and there was no significant difference among the 7 groups (P>0.05). The Ket group had a significantly higher recurrence rate of cough than the other groups (P<0.001), while there was no significant difference in this rate among the other groups (P>0.0024). CONCLUSIONS For children with CVA, a combination of Flu, Mon and Ket has a better clinical effect than a combination of two drugs and a single drug at 2 months of treatment and is safe. After 3 months of treatment, Flu or Mon alone has a similar effect to drug combination. Ket alone has a poor clinical effect and a high recurrence rate after drug withdrawal.
Acetates ; Androstadienes ; Anti-Asthmatic Agents ; Asthma ; drug therapy ; Child ; Cough ; drug therapy ; Drug Combinations ; Fluticasone ; Humans ; Ketotifen ; Quinolines

Mastocytosis is a disorder characterized by abnormal mast cell proliferation and accumulation in one or more tissues. It presents in two major variants: cutaneous mastocytosis and systemic mastocytosis. Because the symptoms are related to mast cells, histamine receptor antagonists and leukotriene receptor antagonists are recommended as therapeutic options. Here, we report a 54-year-old male patient with a history of urticaria pigmentosa who presented with recurrent anaphylaxis. His serum tryptase level was 31.7 ng/mL and mast cell infiltration was observed in his bone marrow. He had frequent attacks of anaphylaxis despite treatment with ketotifen, levocetirizine, and montelukast. Symptoms related to systemic mastocytosis were controlled and the patient exhibited no recurrence of anaphylaxis following the introduction of monthly omalizumab injection. Omalizumab can be considered as a treatment option in patients with systemic mastocytosis unresponsive to conventional oral medications.
Anaphylaxis ; Bone Marrow ; Humans ; Ketotifen ; Leukotriene Antagonists ; Male ; Mast Cells ; Mastocytosis ; Mastocytosis, Cutaneous ; Mastocytosis, Systemic ; Middle Aged ; Omalizumab ; Receptors, Histamine ; Recurrence ; Tryptases ; Urticaria Pigmentosa

Second-generation antihistamines are widely prescribed for the control of symptoms of allergic inflammation such as itchy hives, coryza, and itchy eyes. In rare circumstances, these drugs might provoke allergic inflammation. Hypersensitivity to bepotastine besilate, a second-generation antihistamine has never been reported. A 17-year-old schoolgirl, whose paroxysmal itchy hives had been controlled with bepotastine, experienced aggravation of the hives. An oral provocation test confirmed her hypersensitivity to bepotastine and cross-reactivity to levocetirizine. She showed no reaction to chlorpheniramine, ketotifen, or olopatadine among the 13 antihistamines tested. While searching for an antihistamine to control her itchy hives, we found that she also exhibited cross-reactivity to various antihistamines with different chemical structures from that of bepotastine, which is not predicted according to the chemical classification of antihistamines. We report a case of hypersensitivity to bepotastine besilate in a patient with chronic spontaneous urticaria.
Adolescent ; Chlorpheniramine ; Classification ; Drug Hypersensitivity ; Histamine Antagonists ; Humans ; Hypersensitivity ; Inflammation ; Ketotifen ; Olopatadine Hydrochloride ; Urticaria

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.

Human ; Male ; Infant ; Blister ; Cetirizine ; Diarrhea ; Hyperplasia ; Ketotifen ; Mast Cells ; Mastocytosis ; Mastocytosis, Cutaneous ; Mupirocin ; Nausea ; Vomiting

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.
Histamine ; Histamine Release ; Humans* ; Ketotifen* ; Mast Cells* ; Umbilical Cord* ; Olopatadine Hydrochloride

To analyze the clinical characteristics and combined use of chemical and traditional Chinese medicine (TCM) medicine of hospitalized patients with psoriasis base on real world database, 2 991 cases of hospitalized patients with psoriasis in hospital information system (HIS) database from 16 hospitals in China were analyzed for general hospitalization information, combined diseases and combined use of drugs et al. The results showed that half of inpatients aged 18-45 years old. The most common syndrome of TCM was intrinsic blood heat. More than 1/3 inpatients' hospitalization time was 18-25 days, and the average expense of hospitalization was 6 989. 20 RMB. The top five combined diseases were hypertension, non-alcoholic fatty liver disease, diabetes, upper respiratory tract infection and lipoprotein disorders. Medicine information analysis showed 599 chemical medicines and 341 TCMs were used and combined use of drugs was common in clinical practice. Licorice extract medicine was the most common combined TCM with western medicine; in the next two places were compound Qingdai capsule and tripterygium glycosides. The most common combined use of chemical medicines were Vitamin C, calcium gluconate, ketotifen, cetirizine, retinoic acid and external use glucocorticoid. Anti-inflammatory and liver protection, clearing heat and toxic materials, activating blood and dissolving stasis were the most common combined TCM medicine with western medicine, while the most common combined chemical medicine with TCM were anti-allergic, anti-infection, glucocorticoid and retinoic acid. In conclusion, half of hospitalized patients of psoriasis were young adults. The main type of combined diseases was metabolic disorders and upper respiratory infections. Combined use of chemical medicine and TCM was common in clinical practice. Licorice extract medicine was the most common combined TCM with western medicine.
Adolescent ; Adult ; Aged ; Ascorbic Acid ; therapeutic use ; Calcium Gluconate ; therapeutic use ; Cetirizine ; therapeutic use ; China ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Glucocorticoids ; therapeutic use ; Humans ; Ketotifen ; therapeutic use ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Psoriasis ; drug therapy ; Tretinoin ; therapeutic use ; Young Adult

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.
Blotting, Western ; Breast Neoplasms ; Cell Movement ; Extracellular Matrix ; Fibrosarcoma ; Ketotifen* ; Matrix Metalloproteinase 9 ; Mortality ; Neoplasm Metastasis