• Title/Summary/Keyword: Drug allergy

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An Anti-Cancer Drug Candidate CYC116 Suppresses Type I Hypersensitive Immune Responses through the Inhibition of Fyn Kinase in Mast Cells

  • Park, Young Hwan;Kim, Hyun Woo;Kim, Hyuk Soon;Nam, Seung Taek;Lee, Dajeong;Lee, Min Bum;Min, Keun Young;Koo, Jimo;Kim, Su Jeong;Kim, Young Mi;Kim, Hyung Sik;Choi, Wahn Soo
    • Biomolecules & Therapeutics
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    • v.27 no.3
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    • pp.311-317
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    • 2019
  • Mast cells are the most prominent effector cells of Type 1 hypersensitivity immune responses. CYC116 [4-(2-amino-4-methyl-1,3-thiazol-5-yl)-N-[4-(morpholin-4-yl)phenyl] pyrimidin-2-amine] is under development to be used as an anti-cancer drug, but the inhibitory effects of CYC116 on the activation of mast cells and related allergy diseases have not reported as of yet. In this study, we demonstrated, for the first time, that CYC116 inhibited the degranulation of mast cells by antigen stimulation ($IC_{50}$, ${\sim}1.42{\mu}M$). CYC116 also inhibited the secretion of pro-inflammatory cytokines including TNF-${\alpha}$ ($IC_{50}$, ${\sim}1.10{\mu}M$), and IL-6 ($IC_{50}$, ${\sim}1.24{\mu}M$). CYC116 inhibited the mast cell-mediated allergic responses, passive cutaneous anaphylaxis (ED50, ~22.5 mg/kg), and passive systemic anaphylaxis in a dose-dependent manner in laboratory experiments performed on mice. Specifically, CYC116 inhibited the activity of Fyn in mast cells and inhibited the activation of Syk and Syk-dependent signaling proteins including LAT, $PLC{\gamma}$, Akt, and MAP kinases. Our results suggest that CYC116 could be used as an alternative therapeutic medication for mast cell-mediated allergic disorders, such as atopic dermatitis and allergic rhinitis.

Therapeutic Effect of Bee Venom in Calves with Bacterial Diarrhea (송아지의 세균성 설사증에 관한 생봉독의 치료효과)

  • 최석화;조성구;최춘순;강성수;박석천
    • Journal of Veterinary Clinics
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    • v.17 no.1
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    • pp.57-61
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    • 2000
  • This study was designed to examine therapeutic effect of bee(Apis mellifera L.) venom in calves with bacterial diarrhea. Calves with bacterial diarrhea were administered with bee venom and therapeutic drug, respectively. In the bee venom-treated group, 69 calves were acupunctured once a day for 3 conseutive days. Two local acupoints of Jiao-chao(GV-1, at the indentation between the base of tail and the anus) and Bai-hui(GV -20, in the dorsal midline of the lumbo-sacral space) were stung by the bee. In the therapeutic drug-treated group, 55 claves were intramuscularly injected with a standard dosage of antibiotic (ciprofloxacin, 2.5 mg/kg of body weight) and antidiarrheal drug (berberine cholride, 10mg/head) once a day for 3 consecutive days. At post-treatment, 81.2% of the bee venom-treated calves and 76.4% of the therapeutic drugtreated calves were recovered from bacterial diarrhea. Bee acupuncture therapy showed in calves without side effects such as allergy hemorrhage, or infection. It might be concluded that apitherapy was affective in controlling of calves with bacterial diarrhea.

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Immunomodulatory Effects of Ambroxol on Airway Hyperresponsiveness and Inflammation

  • Katsuyuki Takeda;Nobuaki Miyahara;Shigeki Matsubara;Christian Taube;Kenichi Kitamura;Astushi Hirano;Mitsune Tanimoto;Erwin W. Gelfand
    • IMMUNE NETWORK
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    • v.16 no.3
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    • pp.165-175
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    • 2016
  • Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge. Cytokine production levels from lung mononuclear cells (Lung MNCs) or alveolar macrophages (AM) were also determined. Administration of ambroxol prior to challenge suppressed AHR, airway eosinophilia, goblet cell metaplasia, and reduced inflammation in subepithelial regions. When given after challenge, AHR was suppressed but without effects on eosinophil numbers. Levels of IL-5 and IL-13 in BAL fluid were decreased when the drug was given prior to challenge; when given after challenge, increased levels of IL-10 and IL-12 were detected. Decreased levels of protein carbonyls were detected in BAL fluid following ambroxol treatment after challenge. In vitro, ambroxol increased levels of IL-10, IFN-γ, and IL-12 from Lung MNCs and AM, whereas IL-4, IL-5, and IL-13 production was not altered. Taken together, ambroxol was effective in preventing AHR and airway inflammation through upregulation of Th1 cytokines and protection from oxidative stress in the airways.

Loculated Tuberculous Pleural Effusion: Easily Identifiable and Clinically Useful Predictor of Positive Mycobacterial Culture from Pleural Fluid

  • Ko, Yousang;Kim, Changhwan;Chang, Boksoon;Lee, Suh-Young;Park, So Young;Mo, Eun-Kyung;Hong, Su Jin;Lee, Myung Goo;Hyun, In Gyu;Park, Yong Bum
    • Tuberculosis and Respiratory Diseases
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    • v.80 no.1
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    • pp.35-44
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    • 2017
  • Background: Isolation of M. tuberculosis (MTB) is required in cases of Tuberculous pleural effusion (TBPE) for confirming diagnosis and successful therapy based on drug sensitivity test. Several studies have focused on predictors of MTB culture positivity in TBPE. However, the clinical role of loculated TBPE as a predictor of MTB cultivation from TBPE remains unclear. The aim of this study was to examine possible predictors including loculation of TBPE of MTB culture positivity in TBPE. Methods: We retrospectively examined associations between clinical, radiological, microbiological, and laboratory characteristics and positive MTB culture from TBPE to determine a potent predictor of culture positivity. Results: From January 2011 to August 2015, 232 patients with TBPE were identified. Of these, 219 were finally analyzed. Among them, 69 (31.5%) were culture positive for MTB in TBPE and 86 (39.3%) had loculated TBPE. In multivariate logistic regression analysis, the loculation of TBPE was independently associated with culture positivity for MTB in TBPE (adjusted odds ratio [OR], 40.062; 95% confidence interval [CI], 9.355-171.556; p<0.001). In contrast, the lymphocyte percentage of TBPE (adjusted OR, 0.934; 95% CI, 0.899-0.971; p=0.001) was inversely associated with culture positivity for MTB in TBPE. Conclusion: In clinical practice, identification of loculation in TBPE is easy, reliable to measure, not uncommon and may be helpful to predict the possibility of positive mycobacterial culture.

Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model

  • An, Tai Joon;Rhee, Chin Kook;Kim, Ji Hye;Lee, Young Rong;Chon, Jin Young;Park, Chan Kwon;Yoon, Hyoung Kyu
    • Tuberculosis and Respiratory Diseases
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    • v.81 no.1
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    • pp.80-87
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    • 2018
  • Background: Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of $T_H2$ process and increased $T_H1$ and/or $T_H17$ process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids. Methods: C57BL/6 female mice were sensitized with ovalbumin (OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone (DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were sacrificed. Results: Airway resistance in the OVA+LPS exposed mice was elevated but was more attenuated after treatment with CAM+DXM compared with the monotherapy group (p<0.05 and p<0.01). In bronchoalveolar lavage fluid study, total cells and neutrophil counts in OVA+LPS mice were elevated but decreased after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated group showed less inflammation additively than the monotherapy group. There was less total protein, interleukin 17 (IL-17), interferon ${\gamma}$, and tumor necrosis factor ${\alpha}$ in the CAM+DXM group than in the monotherapy group (p<0.001, p<0.05, and p<0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the DXM and CAM+DXM challenged groups than in the control group (p<0.05). Conclusion: Decreased IL-17 and recovered relative HDAC2 activity correlated with airway resistance and inflammation in a neutrophilic asthma mouse model. This result suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic asthma.

Clinical validation of ImmuneCheck IgE for the rapid detection of serum total IgE (총 IgE의 신속한 정량 측정을 위한 ImmuneCheck IgE의 임상적 유용성)

  • Lee, Shinhaeng;Choi, Jinyoung;Choe, Eunju;Lee, Sang Chul;Park, Kyung Hee;Lee, Jae-Hyun;Park, Jung-Won
    • Allergy, Asthma & Respiratory Disease
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    • v.6 no.6
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    • pp.310-314
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    • 2018
  • Purpose: Conventional serum IgE assay was costly, required the skills of expert, and relied heavily on expensive equipment. Quantitative measurement of total IgE using Point of Care Test (POCT) device can be the solution for these limitations. This study evaluated and validated the reproducibility of ImmuneCheck IgE. Methods: This study included 120 patients of allergic diseases such as allergic rhinitis, asthma, drug allergy, food allergy, atopic dermatitis, or anaphylaxis. The reliability of POCT ImmuneCheck IgE was evaluated by comparing results from the naked eye and from the Q-Reader. Intratest reproducibility and intertest correlation were analyzed using intraclass correlation coefficient (ICC). Results: Of the 120 enrolled patients, 51 were males and 69 were females. The ages ranged from 19 to 84 years, with an average age of 51.5 years. The concentration of serum total IgE measured by Phadia ImmunoCAP IgE ranged from 5.95 to 5,000 IU/mL. ICC for Intratest reproducibility of ImmuneCheck IgE by naked eye and by Q-Reader were 0.991 (P< 0.001) and 0.989 (P< 0.001), respectively. In addition, intertest correlation between ImmuneCheck IgE and Phadia ImmunoCAP IgE results of naked eye and Q-Reader were 0.968 (P< 0.001) and 0.948 (P< 0.001), respectively. Conclusion: The ImmuneCheck IgE was reproducible and highly correlated with conventional Phadia ImmunoCAP IgE assay. This result suggests that ImmuneCheck IgE can be a useful tool for rapid and precise detection of total IgE.

The Relationships between Allergy and Weakness in Children in Seong-Dong District (성동구내 어린이집 어린이의 알레르기 질환과 허약아의 실태 및 관련성에 대한 보고)

  • Park, You-Jin;Yoon, Ji-Yeon;Myoung, Sung-Min
    • The Journal of Pediatrics of Korean Medicine
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    • v.24 no.2
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    • pp.112-125
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    • 2010
  • Objectives The purpose of this study is to find the relationships between the allergy and weakness in children in Seong-Dong district. Methods 802 day care centers children were participated for survey on allergic disease, risk factors, and weakness. From the result, we analyzed the relationships between the aforementioned factors. Results 1. 802 children were participated for the survey. We eliminated survey answers with unclear answers, and selected 792 survey sheets as our final subject of study. The age of majority of subjects(720 children) were between one to six years old, and the others were under the age of one and over seven. 2. The prevalence rate of asthma in a lifetime was 6.69%, allergic rhinitis was 14.87%, atopic dermatitis was 28.82%, allergic conjunctivitis was 6.29%, food allergies was 9.58%, and drug allergies was 1.4%. In 2009, the prevalence rate of allergies during treatments is 6.69% for asthma, 13.41% for allergic rhinitis, 13.64% for atopic dermatitis, 4.13% for allergic conjunctivitis, 5.23% for food allergies, 0.96% for drug allergies. 3. The significant risk factors were types of dwelling, pet with fur, dirty environments without vacuum cleaners, the numbers of times bed covers were washed, frequency of air ventilation, changes in body after moving, family history. 4. The distribution of the number of children with weakness within the five visceras were respiratory weakness, digestive weakness, psychoneurologic weakness, neuromotor weakness, and urogenital weakness in the order of most to the least. More specifically, children who only has respiratory weakness were the majority, while children who have respiratory and digestive weaknesses, children who have respiratory, digestive, and psychoneurologic weaknesses, children who have respiratory and psychoneurologic were followed. 5. With the exception of children with urogenital weakness, Most of the children with respiratory weakness, digestive weakness, psychoneurologic weakness, and neuromotor weakness had been treated for allergies in 2009, while children who were diagnosed with allergic diseases at least once in their lifetime most likely had weak respiratory, digestive or psychoneurologic systems. Conclusions The results of this study showed that there was a correlation between children with weak viscera and children with allergic diseases. However, further research would be necessary.

Pharmaceutical Studies on Microencapsulated Pivampicillin Hydrochloride (염산피밤피실린의 마이크로캅셀에 관(關)한 약제학적(藥劑學的) 연구(硏究))

  • Lee, Wan-Ha;Jee, Ung-Kil;Lee, Young-Hwan;Kim, Sang-Rin
    • Journal of Pharmaceutical Investigation
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    • v.15 no.2
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    • pp.53-62
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    • 1985
  • Pivampicillin hydrochloride is a kind of broad spectrum antibiotics with bactericidal action, and is used in many countries, although it has bitter taste, unpleasant odour and side effects of irritating gastric mucosa, nausea, penicillin allergy, etc. For the improvement of such side effects of pivampicillin hydrochloride, microcapsules, with wall of ethylcellulose, have been prepared by coacervation method. The shape was observed through the scanning electron microscope, the release of the drug into an aqueous medium was studied and the effects of core: ethylcellulose ratio were interpreted as well as making sensory evaluation of taste and odour. There was decreasing trend in dissolution rate of the drug with the increase of core: ethylcellulose ratios, and the smaller microcapsules released their contents more rapidly. A linear relationship was established between the amount of ethylcellulose and the time for 60% release of the drug, and the release pattern was found to have similar characteristics to the release of the drug from an insoluble porous matrix. The release of the drug in the artificial intestinal fluids (pH 6.8) was found to be similar to that in water, while the release in the artificial gastric juice (pH 1.2) was slightly slower. Bioavailability of microcapsule was compared with that of pivampicillin hydrochloride in rabbits using serum concentration and urinary excretion measurements. Microcapsule gave showed slightly higher serum level than pivampicillin hydrochloride from 2 hours after administration, while no significant difference was observed in the accumulated urinary excretion rate between pivampicillin hydrochloride and microcapsule. The ulcer index of pivampicillin hydrochloride administered group was 2.6, and microcapsule administered group was 1.5, while control group was 0.8. Therefore it may be concluded that microencapsulation of pivampicillin hydrochloride is a useful pharmaceutical approach to protect the gastrointestinal tract from being injured by direct contact of pivampicillin hydrochloride without any significant difference of bioavailability.

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A Survey of Drug Intoxication Patients Transferred by 119 Ambulance Service - Seocho area in Seoul - (일 지역 119구급대를 통한 약물중독 사례 고찰 - 서울시 서초지역 중심 -)

  • Cho Wonsun
    • Journal of Korean Public Health Nursing
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    • v.10 no.1
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    • pp.106-117
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    • 1996
  • This study aims to provide information about the acute poisoning patients transferred by 119 ambulance service for nurses and emergency medical technicians. The data is based on 119 ambulance services patients charts of Seocho area in Seoul. The results were as follows: 1. Total number of emergency patients all over the country has been nearly fourtimes in 1995 compared to 1991. Total number of emergency patients were 322.051 in 1994. 2. About $35\%$ of total E.R. patients were transferred by 119 ambulance services in Seoul in the last 5years. Acute drug intoxication patients occupied $2-3\%$ of E.R. patients in Seoul. 3. About $4\%$ of E.R. patients in Seoul were transferred by 119 E.R. services of Seocho area in Seoul in 1995. Among them $2.4\%$ patients were drug intoxication patients. 4. Data were collected from available patients of 119 ambulance services from Jan. 1993 to Dec. 1995 in Seocho area. Total poisoning patients were 184. - The female/male ratio was 69.7:30.4 and most of patients$(69.7\%)$ were in the age of 20th and 30th. - The busy time of calling 119 ambulance service was from 6P.M. to midnight$(37.5\%)$ - It took within 10 minutes for patients$(62.8\%)$ from notification to arrival in hospital. - Regarding poisoning substances. hypnotics $(22.8\%)$, tranquilizer$(14.7\%)$, agricultural agents$(6.0\%)$ rodenticide$(27\%)$ and others $(10.3\%)$ were in order and unknown were $43.5\%$. - Most of the patients or protector $(72.8\%)$ chose hospitals. Among them $(87.3\%)$ were general hospital. - The most predominant symptoms were coma$(22.3\%)$. dizziness$(6.5\%)$ and then allergy. vomiting. gastrointestinal cramps etc. - Airway management and oxygen administration together was the main medical control of prehospital emergency medical services$(33.7\%)$. It is proposed that first, a systematic survey of drug intoxication patients must be conducted to give an appropriate prehospital emergency care for the emergency medical technician and second, a wide and regular public education to improve understanding of first aids should be undertaken.

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A Paragonimiasis Patient with Allergic Reaction to Praziquantel and Resistance to Triclabendazole: Successful Treatment after Desensitization to Praziquantel

  • Kyung, Sun-Young;Cho, Yong-Kyun;Kim, Yu-Jin;Park, Jeong-Woong;Jeong, Sung-Hwan;Lee, Jae-Ik;Sung, Yon-Mi;Lee, Sang-Pyo
    • Parasites, Hosts and Diseases
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    • v.49 no.1
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    • pp.73-77
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    • 2011
  • Paragonimiasis is an infectious disease caused by trematodes of the genus Paragonimus. This trematode can be treated successfully with praziquantel in more than 90% of the cases. Although praziquantel is generally well tolerated, anaphylactic reactions to this drug have been reported in a few cases. We report here a 46-year-old Korean female with paragonimiasis, presumed to be due to Paragonimus westermani, who displayed an allergic reaction to praziquantel and resistance to triclabendazole treatment. The patient was successfully treated with praziquantel following a rapid desensitization procedure. Desensitization to praziquantel could be considered when no alternative drugs are available.