Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide ( 1 ). Dyslipidemia has been shown to be one of the most potent risk factors for coronary heart disease (CHD) ( 2, 3 ). Dyslipidemia is characterized by elevated plasma cholesterol, especially low density lipoprotein cholesterol (LDL-c) levels. Management of dyslipidemia is considered throughout the primary and secondary prevention of CHD ( 4 ). For the past 20 years, the statin (3-hydroxy-3-methylglutaryl CoA reductase inhibitors) class of cholesterol-lowering drugs has been used for the treatment of hypercholesterolemia, either alone or in combination with other classes of lipid-lowering drugs Abstract In an attempt to understand the applicability of various animal models to dyslipidemia in humans and to identify improved preclinical models for target discovery and validation for dyslipidemia, we measured comprehensive plasma lipid profi les in 24 models. These included fi ve mouse strains, six other nonprimate species, and four nonhuman primate (NHP) species, and both healthy animals and animals with metabolic disorders. Dyslipidemic humans were assessed by the same measures. Plasma lipoprotein profi les, eight major plasma lipid fractions, and FA compositions within these lipid fractions were compared both qualitatively and quantitatively across the species. Given the importance of statins in decreasing plasma low-density lipoprotein cholesterol for treatment of dyslipidemia in humans, the responses of these measures to simvastatin treatment were also assessed for each species and compared with dyslipidemic humans. NHPs, followed by dog, were the models that demonstrated closest overall match to dyslipidemic humans. For the subset of the dyslipidemic population with high plasma triglyceride levels, the data also pointed to hamster and db/db mouse as representative models for practical use in target validation. Most traditional models, including rabbit, Zucker diabetic fatty rat, and the majority of mouse models, did not demonstrate overall similarity to dyslipidemic humans in this study . -
Nonsteroidal anti-inf lammatory drugs (NSAIDs) are widely prescribed for the treatment of inflammatory diseases, but their use is frequently related to hypersensitivity reactions. This review outlines our current knowledge of NSAID hypersensitivity (NHS) with regard to its pathogenic, molecular, and genetic mechanisms, as well as diagnosis and treatment. The presentation of NHS varies from a local (skin and/or airways) reaction to systemic reactions, including anaphylaxis. At the molecular level, NHS reactions can be classified as cross-reactive (mediated by cyclooxygenase inhibition) or selective (specific activation of immunoglobulin E antibodies or T cells). Genetic polymorphisms and epigenetic factors have been shown to be closely associated with NHS, and may be useful as predictive markers. To diagnose NHS, inhalation or oral challenge tests are applied, with the exclusion of any cross-reactive NSAIDs. For patients diagnosed with NHS, absolute avoidance of NSAIDs/aspirin is essential, and pharmacological treatment, including biologics, is often used to control their respiratory and cutaneous symptoms. Finally, desensitization is recommended only for selected patients with NHS. However, further research is required to develop new diagnostic methods and more effective treatments against NHS.
The objective of the current study was to evaluate the mechanism of absorption and metabolism of a PEGylated peptide, MRL-1 (46 kDa), after s.c. dosing in dogs and rats. Thoracic lymph ductcannulated (LDC) dog and rat models were developed that allowed continuous collection of lymph for up to 8 days. When [ 3 H]MRL-1 was administered s.c. to LDC dogs, ∼73% of the administered radioactivity was recovered in pooled lymph over a period of 120 hours, suggesting that lymphatic uptake is the major pathway of s.c. absorption for this peptide. In agreement with these data, the systemic exposure of radioactivity related to [
Multifactorial assessments, including comorbidities, treatment adherence, and polypharmacy, are important for better asthma control in elderly asthmatic patients. Further studies on the strategy for the management of elderly asthmatic patients in a real-world setting are warranted.
Table of ContentsA1 Pirfenidone inhibits TGF-b1-induced extracellular matrix production in nasal polyp-derived fibroblastsJae-Min Shin, Heung-Man Lee, Il-Ho ParkA2 The efficacy of a 2-week course of oral steroid in the treatment of chronic spontaneous urticaria refractory to antihistaminesHyun-Sun Yoon, Gyeong Yul ParkA3 The altered distribution of follicular t helper cells may predict a more pronounced clinical course of primary sjögren’s syndromeMargit ZeherA4 Betamethasone suppresses Th2 cell development induced by langerhans cell like dendritic cellsKatsuhiko Matsui, Saki Tamai, Reiko IkedaA5 An evaluation of variousallergens in cases of allergic bronchial asthma at lucknow and neighbouring districts by intradermal skintestDrsushil Suri, Dranu SuriA6 Evaluation ferqency of ADHD in childhood asthmaMarzieh Heidarzadeh AraniA7 Steven johnson syndrome caused by typhoid fever in a childAzwin Lubis, Anang EndaryantoA8 Chronic Bronchitis with Radio Contrast Media Hypersensitivity: A Case with Hypothesized GINA Step 1 AsthmaShinichiro KogaA9 The association between asthma and depression in Korean adult : An analysis of the fifth korea national health and nutrition examination survey (2010-2012)Lee Ju SukA10 Management of allergic disease exacerbations in pregnancyYasunobu TsuzukiA11 Subcutaneous immunotherapy mouse model for atopic dermatitisSeo Hyeong Kim, Jung U Shin, Ji Yeon Noh, Shan Jin, Shan Jin, Hemin Lee, Jungsoo Lee, Chang Ook Park, Kwang Hoon Lee, Kwang Hoon LeeA12 Atopic disease and/or atopy are risk factors for local anesthetic allergy in patients with history of hypersensitivity reactions to drugs?Fatma Merve TepetamA13 Food hypersensitivity in patients with atopic dermatitis in KoreaChun Wook Park, Jee Hee Son, Soo Ick Cho, Yong Se Cho, Yun Sun Byun, Yoon Seok Yang, Bo Young Chung, Hye One Kim, Hee Jin ChoA14 Anaphylaxis caused by an ant (Brachyponera chinensis) in JapanYoshinori Katada, Toshio Tanaka, Akihiko Nakabayashi, Koji Nishida, Kenichi Aoyagi, Yuki Tsukamoto, Kazushi Konma, Motoo Matsuura, Jung-Won Park, Yoshinori Harada, Kyoung Yong Jeong, Akiko Yura, Maiko YoshimuraA15 Anti-allergic effect of anti-IL-33 by suppression of immunoglobulin light chain and inducible nitric oxide synthaseTae-Suk Kyung, Young Hyo Kim, Chang-Shin Park, Tae Young Jang, Min-Jeong Heo, Ah-Yeoun Jung, Seung-Chan YangA16 Food hypersensitivity in patients with chronic urticaria in KoreaHye One Kim, Yong Se Cho, Yun Sun Byun, Yoon Seok Yang, Bo Young Chung, Jee Hee Son, Chun Wook Park, Hee Jin ChoA17 Dose optimizing study of a depigmented polymerized allergen extract of phleum pollen by means of conjunctival provocation test (CPT)Angelika Sager, Oliver PfaarA18 Correlation of cutaneous sensitivity and cytokine response in children with asthmaAmit Agarwal, Meenu Singh, Bishnupda Chatterjee, Anil ChauhanA19 Colabomycin E, a Streptomycete-Derived Secondary Metabolite, Inhibits Proinflammatory Cytokines in Human Monocytes/MacrophagesIlja Striz, Eva Cecrdlova, Katerina Petrickova, Libor Kolesar, Alena Sekerkova, Veronika Svachov...
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