PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry. METHODS: A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids. RESULTS: A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals. CONCLUSIONS: The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.
Acetaminophen ; Acetates ; Acetic Acid ; Anti-Inflammatory Agents, Non-Steroidal ; Cicatrix ; Classification ; Cyclooxygenase 2 Inhibitors ; Diethylpropion ; Drug Hypersensitivity ; Drug Hypersensitivity Syndrome ; Hospitals, University ; Incidence ; Korea ; Phenotype ; Propionates ; Prospective Studies ; Retrospective Studies ; Salicylates ; Salicylic Acid ; Stevens-Johnson Syndrome

Abdominal Pain ; Acidosis ; Child ; Child, Preschool ; Diagnosis ; Diethylpropion ; Humans ; Hyperammonemia ; Inpatients ; Metabolic Diseases ; Methylmalonyl-CoA Decarboxylase ; Molecular Biology ; Muscle Hypotonia ; Pancreatitis ; Parenteral Nutrition, Total ; Propionic Acidemia ; Seizures ; Shock ; Vomiting

Staphylococcus aureus, a Gram-positive pathogen, can cause severe inflammation in humans, leading to various life-threatening diseases. The lipoprotein is a major virulence factor in S. aureus-induced infectious diseases and is responsible for excessive inflammatory mediators such as nitric oxide (NO). Short-chain fatty acids (SCFAs) including butyrate, propionate, and acetate are microbial metabolites in the gut that are known to have anti-inflammatory effects in the host. In this study, we investigated the effects of SCFAs on S. aureus lipoprotein (Sa.LPP)-induced NO production in mouse macrophages. Butyrate and propionate, but not acetate, inhibited Sa.LPP-induced production of NO in RAW 264.7 cells and bone marrow-derived macrophages. Butyrate and propionate inhibited Sa.LPP-induced expression of inducible NO synthase (iNOS). However, acetate did not show such effects under the same conditions. Furthermore, butyrate and propionate, but not acetate, inhibited Sa.LPP-induced activation of NF-κB, expression of IFN-β, and phosphorylation of STAT1, which are essential for inducing transcription of iNOS in macrophages. In addition, butyrate and propionate induced histone acetylation at lysine residues in the presence of Sa.LPP in RAW 264.7 cells. Moreover, Sa.LPP-induced NO production was decreased by histone deacetylase (HDAC) inhibitors. Collectively, these results suggest that butyrate and propionate ameliorate the inflammatory responses caused by S. aureus through the inhibition of NF-κB, IFN-β/STAT1, and HDAC, resulting in attenuated NO production in macrophages.
Acetylation ; Animals ; Butyrates ; Communicable Diseases ; Diethylpropion ; Fatty Acids, Volatile ; Histone Deacetylase Inhibitors ; Histone Deacetylases ; Histones ; Humans ; Inflammation ; Lipoproteins ; Lysine ; Macrophages ; Mice ; Nitric Oxide Synthase ; Nitric Oxide ; Phosphorylation ; RAW 264.7 Cells ; Staphylococcus aureus ; Virulence

Albizzia julibrissin (AJ) is an herbal medicine that shows low toxicity, promotes promoting blood circulation and mitigates the inflammation and has mild side effects. Benign prostate hyperplasia (BPH) is one of the most common diseases that occurs in older males and often results in lower urinary tract symptoms. This study was conducted to evaluate the protective effect of AJ against BPH using LNCaP cells and Sprague Dawley rats treated with testosterone. Treatment with AJ extract reduced the expression of androgen receptor (AR) and prostate-specific antigen (PSA) in vitro. In vivo, rats were divided into 6 groups: 1 (Normal Control); 2 (Testosterone propionate (TP) alone); 3 (TP + finasteride); 4 (TP + AJ 10 mg/kg); 5 (TP + AJ 50 mg/kg); 6 (TP + AJ 300 mg/kg). The groups treated with AJ showed reduced the relative prostate weights and BPH-related proteins were altered, with decreased AR, PSA and proliferating cell nuclear antigen (PCNA) observed by western blot. Histopathological analysis revealed the therapeutic effect of AJ, with a decreased thickness of epithelial cells and reduced level of PCNA and 5α-reductase type 2. These results suggest that AJ extract could ameliorate testosterone-induced benign prostatic hyperplasia.
Albizzia ; Animals ; Blood Circulation ; Blotting, Western ; Diethylpropion ; Epithelial Cells ; Herbal Medicine ; Humans ; Hyperplasia ; In Vitro Techniques ; Inflammation ; Lower Urinary Tract Symptoms ; Male ; Proliferating Cell Nuclear Antigen ; Prostate ; Prostate-Specific Antigen ; Prostatic Hyperplasia ; Rats ; Rats, Sprague-Dawley ; Receptors, Androgen ; Testosterone ; Weights and Measures

BACKGROUND: Adverse cutaneous drug reactions (ACDRs) are common and are responsible for increased morbidity, mortality, and socioeconomic costs. OBJECTIVE: The purpose of our study was to investigate the common drugs and clinical patterns related to ACDRs using an electronic drug adverse reaction reporting system at a single secondary referral center. METHODS: We conducted a retrospective analysis of the ACDR database between January 2014 and April 2016 at the Ilsan Paik Hospital. RESULTS: The study analyzed 320 patients with ACDRs (male:female ratio=93:227; mean age 50.8±17.8 years). Using a Korean causality evaluation algorithm, the percentage of drugs with a possible relationship with ACDRs was calculated to be 50.6%, while the percentage with a probable relationship was 44.7%. Antibiotics (44.0%), radiocontrast media (15.1%), and non-steroidal anti-inflammatory drugs (NSAIDs) (14.3%) were the most commonly implicated drugs. Antibiotics, including cephalosporins (30.6%) and quinolones (10.2%), were responsible for the majority of the ACDRs. Acetic acid (5.9%) and propionic acid (5.9%) derivatives of NSAIDs were also common causative agents. The most common clinical presentations were maculopapular exanthema (33.4%), pruritus (30.9%), and urticaria (25.7%). Severe ACDRs were significantly associated with older age, eosinophilia, and underlying heart and renal diseases (p<0.05). CONCLUSION: Antibiotics, radiocontrast media, and NSAIDs were identified as common causes of ACDRs. Older age, eosinophilia, heart disease, and renal disease were associated with severe ACDRs.
Acetic Acid ; Adverse Drug Reaction Reporting Systems ; Anti-Bacterial Agents ; Anti-Inflammatory Agents, Non-Steroidal ; Cephalosporins ; Contrast Media ; Diethylpropion ; Drug-Related Side Effects and Adverse Reactions ; Eosinophilia ; Exanthema ; Heart ; Heart Diseases ; Humans ; Mortality ; Pruritus ; Quinolones ; Retrospective Studies* ; Secondary Care Centers* ; Urticaria

PURPOSE: Extrafine-particle inhaled corticosteroids (ICS) have greater small airway deposition than standard fine-particle ICS. We sought to compare asthma-related outcomes after patients initiated extrafine-particle ciclesonide or fine-particle ICS (fluticasone propionate or non-extrafine beclomethasone). METHODS: This historical, matched cohort study included patients aged 12-60 years prescribed their first ICS as ciclesonide or fine-particle ICS. The 2 cohorts were matched 1:1 for key demographic and clinical characteristics over the baseline year. Co-primary endpoints were 1-year severe exacerbation rates, risk-domain asthma control, and overall asthma control; secondary endpoints included therapy change. RESULTS: Each cohort included 1,244 patients (median age 45 years; 65% women). Patients in the ciclesonide cohort were comparable to those in the fine-particle ICS cohort apart from higher baseline prevalence of hospitalization, gastroesophageal reflux disease, and rhinitis. Median (interquartile range) prescribed doses of ciclesonide and fine-particle ICS were 160 (160-160) µg/day and 500 (250-500) µg/day, respectively (P<0.001). During the outcome year, patients prescribed ciclesonide experienced lower severe exacerbation rates (adjusted rate ratio [95% CI], 0.69 [0.53-0.89]), and higher odds of risk-domain asthma control (adjusted odds ratio [95% CI], 1.62 [1.27-2.06]) and of overall asthma control (2.08 [1.68-2.57]) than those prescribed fine-particle ICS. The odds of therapy change were 0.70 (0.59-0.83) with ciclesonide. CONCLUSIONS: In this matched cohort analysis, we observed that initiation of ICS with ciclesonide was associated with better 1-year asthma outcomes and fewer changes to therapy, despite data suggesting more difficult-to-control asthma. The median prescribed dose of ciclesonide was one-third that of fine-particle ICS.
Adrenal Cortex Hormones* ; Anti-Asthmatic Agents ; Asthma ; Cohort Studies ; Comparative Effectiveness Research ; Diethylpropion ; Disease Progression ; Gastroesophageal Reflux ; Hospitalization ; Humans ; Odds Ratio ; Prevalence ; Rhinitis

PURPOSE: Most of the atopic dermatitis (AD) patients and their parents refuse topical treatment because of concern about generalized side effect due to systemic absorption of topical corticosteroids. Therefore, a large number of studies reported difficulty in properly controlling in AD. However, investigations of the percutaneous absorption of topical corticosteroids are still insufficient. METHODS: One hundred nine patients who visited our atopy clinic and diagnosed as AD by a physician from January 2005 to January 2012 were enrolled. We examined serum corticosteroid (clobetasol propionate, hydrocortisone) level by liquid chromatography (LC) coupled with a tandem mass spectrometric (MS/MS) method. RESULTS: We developed the LC-MS/MS method to determine corticosteroids (clobetasol propionate, hydrocortisone) in sera of AD patients. Also, we confirmed precision, accuracy, limit of detection, limit of quantification, absolute recovery, and relative recovery of the experimental methods. We could not detect clobetasol propionate or hydrocortisone in sera of 109 AD patients using the newly developed LC-MS/MS method. CONCLUSION: Regardless of age, the severity and illness duration of AD, clobetasol and hydrocortisone were not detected in sera. Although there are many other factors of determining systemic absorption of topical medications, our results showed that topical corticosteroids applied for several years in AD patients may be under the limit of detection in their sera by the LC-MS/MS method.
Absorption, Physiological ; Adrenal Cortex Hormones* ; Chromatography, Liquid ; Clobetasol ; Dermatitis, Atopic* ; Diethylpropion ; Humans ; Hydrocortisone ; Limit of Detection ; Methods ; Parents ; Skin Absorption

PURPOSE: No studies have been conducted to investigate the acute toxicity of aryloxyphenoxypropionate herbicides in humans following ingestion. Therefore, this study was conducted to investigate the clinical characteristics of aryloxyphenoxypropionate herbicide poisoning and provide guidance for physicians treating patients who have ingested these types of herbicides. METHODS: A retrospective observational case series was conducted using ten patients with history of aryloxyphenoxy propionate herbicide. Data were collected for clinical manifestation, management and final outcome. RESULTS: The most common symptoms were gastrointestinal irritation and an altered mental state (Glasgow Coma Scale<15). An elevated lactate level was a common laboratory abnormality, and prolonged QTc interval was commonly observed. These clinical features normalized within one day of supportive treatment. CONCLUSION: The acute toxicity of aryloxyphenoxypropionate herbicides in humans is manageable with supportive treatment. However, physicians should take into account depressed consciousness, the possibility of arrhythmia, and an elevated lactate level when planning their treatment strategy.
Acetyl-CoA Carboxylase ; Arrhythmias, Cardiac ; Coma ; Consciousness ; Diethylpropion* ; Eating* ; Herbicides ; Humans ; Lactic Acid ; Poisoning ; Retrospective Studies

No abstract available.
Betamethasone* ; Butyrates* ; Diethylpropion* ; Humans* ; Keratinocytes*

Anorexia is one of the most common issues in older patients. Although there is a tendency for loss of appetite in older persons due to decreased physical activity and reduced resting metabolic rate, this physiological anorexia of aging can easily develop into progressive anorexia and weight loss. This pathologic anorexia and resultant weight loss is associated with increased morbidity and mortality, especially in the frail elderly. To prevent older persons from entering a vicious cycle of frailty, that is, anorexia-malnutrition-sarcopenia-functional impairment, routine screening for anorexia and malnutrition should be implemented in geriatric clinical practice. All anorexic elderly patients should be strongly encouraged to maintain their nutrition, and appetite stimulants can be considered if non-pharmacological interventions are not effective. Although there are no US or Korea Food and Drug Administration approved medications for geriatric-specific anorexia and weight loss, several appetite stimulants can be prescribed and are used widely. Megestrol acetate is the most widely studied and commonly used of these drugs. Cyproheptadine, dronabinol, mirtazapine, corticosteroids, anabolic steroids (e.g., testosterone or oxandrolone), and growth hormone are also effective in increasing appetite or weight. However, the use of these orexigenic agents should occur only after their benefit-to-risk ratio has been carefully considered.
Adrenal Cortex Hormones ; Aged ; Aging ; Anorexia ; Appetite Stimulants* ; Appetite* ; Cyproheptadine ; Diethylpropion ; Dronabinol ; Frail Elderly ; Growth Hormone ; Humans ; Korea ; Malnutrition ; Mass Screening ; Megestrol Acetate ; Mortality ; Motor Activity ; Steroids ; Testosterone ; United States Food and Drug Administration ; Weight Loss