Analysis of anticholinergic adverse effects using two large databases: The US Food and Drug Administration Adverse Event Reporting System database and the Japanese Adverse Drug Event Report database.

INTRODUCTION: Anticholinergic adverse effects (AEs) are a problem for elderly people. This study aimed to answer the following questions. First, is an analysis of anticholinergic AEs using spontaneous adverse drug event databases possible? Second, what is the main drug suspected of inducing anticholinergic AEs in the databases? Third, do database differences yield different results? METHODS: We used two databases: the US Food and Drug Administration Adverse Event Reporting System database (FAERS) and the Japanese Adverse Drug Event Report database (JADER) recorded from 2004 to 2020. We defined three types of anticholinergic AEs: central nervous system (CNS) AEs, peripheral nervous system (PNS) AEs, and a combination of these AEs. We counted the number of cases and evaluated the ratio of drug-anticholinergic AE pairs between FAERS and JADER. We computed reporting odds ratios (RORs) and assessed the drugs using Beers Criteria®. RESULTS: Constipation was the most reported AE in FAERS. The ratio of drug-anticholinergic AE pairs was statistically significantly larger in FAERS than JADER. Overactive bladder agents were suspected drugs common to both databases. Other drugs differed between the two databases. CNS AEs were associated with antidementia drugs in FAERS and opioids in JADER. In the assessment using Beers Criteria®, signals were detected for almost all drugs. Between the two databases, a significantly higher positive correlation was observed for PNS AEs (correlation coefficient 0.85, P = 0.0001). The ROR was significantly greater in JADER. CONCLUSIONS: There are many methods to investigate AEs. This study shows that the analysis of anticholinergic AEs using spontaneous adverse drug event databases is possible. From this analysis, various suspected drugs were detected. In particular, FAERS had many cases. The differences in the results between the two databases may reflect differences in the reporting countries. Further study of the relationship between drugs and CNS AEs should be conducted.

Synthesis and biological evaluation of 3-styrylchromone derivatives as selective monoamine oxidase B inhibitors.

A series of 3-styrylchromone derivatives was synthesized and evaluated for monoamine oxidase (MAO) A and B inhibitory activities. Most of all derivatives inhibited MAO-B selectively, except compound 21. Compound 19, which had a methoxy group at R2 on the chromone ring and chlorine at R4 on phenyl ring, potently inhibited MAO-B, with an IC50 value of 2.2 nM. Compound 1 showed the highest MAO-B selectivity, with a selectivity index of >3700. Further analysis of these compounds indicated that compounds 1 and 19 were reversible and mixed-type MAO-B inhibitors, suggesting that their mode of action may be through tight-binding inhibition to MAO-B. Quantitative structure-activity relationship (QSAR) analyses of the 3-styrylchromone derivatives were conducted using their pIC50 values, through Molecular Operating Environment (MOE) and Dragon. There were 1796 descriptors of MAO-B inhibitory activity, which showed significant correlations (P < 0.05). Further investigation of the 3-styrylchromone structures as useful scaffolds was performed through three-dimensional-QSAR studies using AutoGPA, which is based on the molecular field analysis algorithm using MOE. The MAO-B inhibitory activity model constructed using pIC50 value index exhibited a determination coefficients (R2) of 0.972 and a Leave-One-Out cross-validated determination coefficients (Q2) of 0.914. These data suggest that the 3-styrylchromone derivatives assessed herein may be suitable for the design and development of novel MAO inhibitors.

Evaluation of antibiotic-induced taste and smell disorders using the FDA adverse event reporting system database.

Adverse effects can occur owing to anorexia, which can reduce treatment compliance and worsen the patients overall condition. One such side effect, namely drug-induced taste and smell disorders, reduces patients quality of life. Although antibiotics can cause taste and smell disorders, a few studies have examined antibiotic-induced taste and smell disorders. Therefore, this study comprehensively analyzed the relationship between taste and smell disorders and antibiotic usage. The side effects of antibiotics were investigated using the FDA Adverse Event Reporting System database (FAERS). The reporting odds ratios between the listed drugs and taste and smell disorders P values were comprehensively calculated. Adjusted odds ratios were calculated to account for patient background. Furthermore, to clarify the feature of this adverse effect, shape parameters indicating the expression pattern were calculated. Signals that induced taste and smell disorders were detected for six antibiotics, including drugs for which this event is not described in the package insert in Japan. Multiple logistic regression analysis suggested an association of taste and smell disorders with gender, hypertension, mental disorder, and cancer. The median time to onset of antibiotic-induced taste and smell disorders was 2-5 days. Six antibiotics could be analyzed, and four of these drugs matched those with detected signals. Our study supported previous findings on gender and age. Furthermore, antibiotic-induced taste and smell disorders are likely to develop in the early stage of treatment. For these reasons, it is important to remember the risk of developing of taste and smell disorders when administering antibiotics. In addition, it is recommended that the patient be monitored carefully for at least 1 week before initiating treatment, and the patients course should be followed for at least 2 months.

Antitumor Effects and Tumor-specificity of Guaiazulene-3-Carboxylate Derivatives Against Oral Squamous Cell Carcinoma In Vitro.

AIM: The aim of this study was to investigate the antitumor potential of guaiazulene-3-carboxylate derivatives against oral malignant cells. MATERIALS AND METHODS: Twelve guaiazulene-3-carboxylate derivatives were synthesized by introduction of either with alkyl group [1-5], alkoxy group [6, 7], hydroxyl group [8, 9] or primary amine [10-12] at the end of sidechains. Tumor-specificity (TS) was calculated by the ratio of mean 50% cytotoxic concentration (CC50) against 3 human oral mesenchymal cell lines to that against 4 human oral squamous cell carcinoma (OSCC) cell lines. Potency-selectivity expression (PSE) was calculated by dividing TS value by CC50value against OSCC cell lines. Cell cycle analysis was performed by cell sorter. RESULTS: [6, 7] showed the highest TS and PSE values, and induced the accumulation of both subG1 and G2/M cell populations in HSC-2 OSCC cells. Quantitative structure-activity relationship analysis demonstrated that their tumor-specificity was correlated with chemical descriptors that explain the 3D shape, electric state and ionization potential. CONCLUSION: Alkoxyl guaiazulene-3-carboxylates [6, 7] can be potential candidates of lead compound for developing novel anticancer drugs.

Development of Newly Synthesized Chromone Derivatives with High Tumor Specificity against Human Oral Squamous Cell Carcinoma.

Since many anticancer drugs show severe adverse effects such as mucositis, peripheral neurotoxicity, and extravasation, it was crucial to explore new compounds with much reduced adverse effects. Comprehensive investigation with human malignant and nonmalignant cells demonstrated that derivatives of chromone, back-bone structure of flavonoid, showed much higher tumor specificity as compared with three major polyphenols in the natural kingdom, such as lignin-carbohydrate complex, tannin, and flavonoid. A total 291 newly synthesized compounds of 17 groups (consisting of 12 chromones, 2 esters, and 3 amides) gave a wide range of the intensity of tumor specificity, possibly reflecting the fitness for the optimal 3D structure and electric state. Among them, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (compound 22), which belongs to 3-styrylchromones, showed the highest tumor specificity. 22 induced subG1 and G2 + M cell population in human oral squamous cell carcinoma cell line, with much less keratinocyte toxicity as compared with doxorubicin and 5-FU. However, 12 active compounds selected did not necessarily induce apoptosis and mitotic arrest. This compound can be used as a lead compound to manufacture more active compound.

Syntheses and Glycosidase Inhibitory Activities, and in Silico Docking Studies of Pericosine E Analogs Methoxy-Substituted at C6.

Inspired by the significant -glucosidase inhibitory activities of (+)- and (-)-pericosine E, we herein designed and synthesized 16 analogs of these marine natural products bearing a methoxy group instead of a chlorine atom at C6. Four of these compounds exhibited moderate -glucosidase inhibitory activities, which were weaker than those of the corresponding chlorine-containing species. The four compounds could be prepared by coupling reactions utilizing the (-)-pericosine B moiety. An additional in silico docking simulation suggested that the reason of reduced activity of the C6-methoxylated analogs might be an absence of hydrogen bonding between a methoxy group with the surrounding amino acid residues in the active site in -glucosidase.

Further Quantitative Structure-Cytotoxicity Relationship Analysis of 3-Styrylchromones.

BACKGROUND/AIM: Very few studies are available about the biological activity of 3-styrylchromones. Our previous study demonstrated the importance of methoxy group at 6-position of the chromone ring and hydroxyl group at 4'-position of phenyl group in styryl moiety. As a sequel of this study, we synthesized fourteen compounds that include eight 3-styrylchromones where methoxy group was introduced at 7-position of chromone rings, and then evaluated their tumor-specificity. MATERIALS AND METHODS: Tumor-specificity (TS) was calculated by relative cytotoxicity against human oral squamous cell carcinoma cell lines versus human normal oral cells. Apoptosis induction and growth arrest were monitored by cell-cycle analysis. Quantitative structure-activity relationship analysis of TS was performed with 3,167 chemical descriptors. RESULTS AND DISCUSSION: Two compounds, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one [7] and 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one [14] showed higher tumor-specificity than doxorubicin and 5-FU, suggesting the importance of methoxy group in 7-position of the chromone ring. These compounds induced the apoptosis and mitotic arrest in HSC-2 cells. The tumor-specificity of 3-styrylchromone derivatives were most correlated with descriptors for molecule shape and electronic charge. The present study suggested that modification by introducing methoxy group at 7-position, instead at 6-position, further increased the tumor-specificity of 3-styrylchromone.

Quantitative Structure-Cytotoxicity Relationship of 2-Arylazolylchromones and 2-Triazolylchromones.

BACKGROUND/AIM: 4H-1-Benzopyran-4-one (chromone), present in various flavonoids as a backbone structure, has been used for the synthesis of anticancer drugs. The study aimed at investigating the cytotoxicity of eight 2-arylazolylchromones and twelve 2-triazolylchromones against four human oral squamous cell carcinoma (OSCC) cell lines and three human normal mesenchymal oral cells, and then performed a quantitative structure-activity relationship (QSAR) analysis. MATERIALS AND METHODS: Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The distribution of cells to various phases of cell cycle was determined by cell cycle analysis. A total of 3,218 physicochemical, structural and quantum chemical features were calculated for QSAR analysis from the most stabilized structure optimized using CORINA. RESULTS: 2-[4-(4-fluorophenyl)-1H-imidazol-1-yl]-4H-1-benzopyran-4-one [6] had the highest tumor-specificity (TS), comparable with that of 5-flurouracil (5-FU) and doxorubicin, inducing cytostatic growth inhibition, accumulation of G2+M phase cells with no cells in the G1 phase. All eight 2-triazolylchromones showed much lower tumor-specificity, confirming our previous finding. Tumor-specificity was also correlated with 3D shape, topological shape, size, ionization potential, and the presence of more than two aromatic rings in the molecule and imidazole ring in the nitrogen-containing heterocyclic ring. CONCLUSION: [6] can be a lead compound for designing anticancer drugs.

Quantitative Structure-Cytotoxicity Relationship of 2-Styrylchromones.

BACKGROUND/AIM: Studies of biological activity of 2-styrylchromone derivatives focusing on antioxidant, anti-inflammatory, antiviral and antitumor activity are limited. In this study, eighteen synthetic 2-styrylchromone derivatives were investigated for their cytotoxicity against human malignant and non-malignant cells, and then subjected to quantitative structure-activity relationship (QSAR) analysis. MATERIALS AND METHODS: Tumor-specificity was calculated by the ratio of mean 50% cytotoxic concentration (CC50) against four normal oral cells to that against oral squamous cell carcinoma cell lines. Induction of apoptosis and growth arrest were evaluated by cell-cycle analysis. For QSAR analysis, 3,117 types of physicochemical, structural, and quantum chemical features were calculated from the most stabilized structure of 2-styrylchromone derivatives. RESULTS: Two 2-styrylchromone derivatives in which a methoxy group was introduced at the 4-position of the benzene ring showed tumor-specificity equivalent to or higher than doxorubicin in TS value. These compounds accumulated the subG1 and G2/M phase cells, suggesting the induction of apoptosis. Their tumor-specificity can be explained mainly by molecular shape and electronic state. CONCLUSION: These findings suggest the applicability of 2-styrylchromone to develop safe and effective anticancer agents as seed compounds.

2-Styrylchromone derivatives as potent and selective monoamine oxidase B inhibitors.

A series of eighteen 2-styrylchromone derivatives (see Chart 1) were synthesized and evaluated for their monoamine oxidase (MAO) A and B inhibitory activities. Many of the derivatives inhibited MAO-B comparable to pargyline (a positive control), and most of them inhibited MAO-B selectively. Of the eighteen derivatives, compound 9 having methoxy group at R1 and chlorine at R4 showed both the best MAO-B inhibitory activity (IC50 = 17 ±â€¯2.4 nM) and the best MAO-B selectivity (IC50 for MAO-A/IC50 for MAO-B = 1500). The mode of inhibition of compound 9 against MAO-B was competitive and reversible. Quantitative structure-activity relationship (QSAR) analyses of the 2-styrylchromone derivatives were conducted using their pIC50 values with the use of Molecular Operating Environment (MOE) and Dragon, demonstrating that the descriptors of MAO-B inhibitory activity and MAO-B selectivity were 1734 and 121, respectively, that showed significant correlations (P < 0.05). We then examined the 2-styrylchromone structures as useful scaffolds through three-dimensional-QSAR studies using AutoGPA, which is based on the molecular field analysis algorithm using MOE. The model using pIC50 value indexes for MAO-B exhibited a determination coefficient (R2) of 0.873 as well as a Leave-One-Out cross-validated determination coefficient (Q2) of 0.675. These data suggested that the 2-styrylchromone structure might be a useful scaffold for the design and development of novel MAO-B inhibitors.

Quantitative Structure-Cytotoxicity Relationship of Azulene Amide Derivatives.

BACKGROUND/AIM: Very few studies of anticancer activity of azulene amides led us to investigate the cytotoxicity of 21 N-alkylazulene-1-carboxamides introduced either with 3-methyl [1-7], 7-isopropyl-3-methyl [8-14] or 2-methoxy group [15-21] Materials and Methods: Tumor-specificity (TS) was calculated by the ratio of mean 50% cytotoxic concentration (CC50) against three normal human oral mesenchymal cells to that against four human oral squamous cell carcinoma (OSCC) cell lines. Potency-selectivity expression (PSE) was calculated by dividing TS value by CC50 value against OSCC cell lines. Apoptosis-inducing activity was evaluated by caspase-3 activation and appearance of subG1 cell population. RESULTS: [8-14] showed higher TS and PSE values, than [1-7] and [15-21] The most active compound [8-14] induced apoptosis in C9-22 OSCC cells at 4-times higher CC50 Quantitative structure-activity relationship analysis of [1-14] demonstrated that their tumor-specificity was correlated with chemical descriptors that explain the molecular shape and hydrophobicity. CONCLUSION: 7-Isopropyl-3-methyl-N-propylazulene-1-carboxamide [8] can be a potential candidate of lead compound for manufacturing new anticancer drug.

QSAR Prediction Model to Search for Compounds with Selective Cytotoxicity Against Oral Cell Cancer.

Background: Anticancer drugs often have strong toxicity against tumours and normal cells. Some natural products demonstrate high tumour specificity. We have previously reported the cytotoxic activity and tumour specificity of various chemical compounds. In this study, we constructed a database of previously reported compound data and predictive models to screen a new anticancer drug. Methods: We collected compound data from our previous studies and built a database for analysis. Using this database, we constructed models that could predict cytotoxicity and tumour specificity using random forest method. The prediction performance was evaluated using an external validation set. Results: A total of 494 compounds were collected, and these activities and chemical structure data were merged as database for analysis. The structure-toxicity relationship prediction model showed higher prediction accuracy than the tumour selectivity prediction model. Descriptors with high contribution differed for tumour and normal cells. Conclusions: Further study is required to construct a tumour selective toxicity prediction model with higher predictive accuracy. Such a model is expected to contribute to the screening of candidate compounds for new anticancer drugs.

Recent Progress of Basic Studies of Natural Products and Their Dental Application.

The present article reviews the research progress of three major polyphenols (tannins, flavonoids and lignin carbohydrate complexes), chromone (backbone structure of flavonoids) and herbal extracts. Chemical modified chromone derivatives showed highly specific toxicity against human oral squamous cell carcinoma cell lines, with much lower toxicity against human oral keratinocytes, as compared with various anticancer drugs. QSAR analysis suggests the possible correlation between their tumor-specificity and three-dimensional molecular shape. Condensed tannins in the tea extracts inactivated the glucosyltransferase enzymes, involved in the biofilm formation. Lignin-carbohydrate complexes (prepared by alkaline extraction and acid-precipitation) and crude alkaline extract of the leaves of Sasa species (SE, available as an over-the-counter drug) showed much higher anti-HIV activity, than tannins, flavonoids and Japanese traditional medicine (Kampo). Long-term treatment with SE and several Kampo medicines showed an anti-inflammatory and anti-oxidant effects in small size of clinical trials. Although the anti-periodontitis activity of synthetic angiotensin II blockers has been suggested in many papers, natural angiotensin II blockers has not yet been tested for their possible anti-periodontitis activity. There should be still many unknown substances that are useful for treating the oral diseases in the natural kingdom.

Quantitative Structure-Cytotoxicity Relationship of Pyrano[4,3-b]chromones.

BACKGROUND/AIM: 4H-1-Benzopyran-4-one (chromone) provides a backbone structure for the chemical synthesis of potent anticancer drugs. Since studies of the biological activity of pyrano[4,3-b]chromones are limited, we investigated a total of 20 pyrano[4,3-b]chromones (10 sets of diastereomers) for their cytotoxicity against four human oral squamous cell carcinoma (OSCC) cell lines and human normal oral cells, and then carried out a quantitative structure-activity relationship (QSAR) analysis. MATERIALS AND METHODS: Cytotoxicity was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Tumor-specificity (TS) was evaluated by the ratio of mean 50% cytotoxic concentration (CC50) against normal oral cells to that against human OSCC cell lines. Potency-selectivity expression (PSE) value was calculated by dividing the TS value by the CC50 against tumor cells. Apoptosis induction was evaluated by morphological observation, western blot analysis and cell-cycle analysis. For QSAR analysis, a total of 3,072 physicochemical, structural and quantum chemical features were calculated from the most stabilized structure optimized using CORINA. RESULTS: 8-Chloro-4,4a-dihydro-3-methoxy-3-methyl-3H,10H-pyrano[4,3-b][1]benzopyran-10-one (16) and 3-ethoxy-4,4a-dihydro-8-methoxy-3H,10H-pyrano[4,3-b][1]benzopyran-10-one (17) had the highest TS, higher than that of 5-flurouracil and melphalan, without induction of apoptosis. Compound 16 induced cytostatic growth inhibition and much lower cytotoxicity against human normal oral keratinocytes compared to doxorubicin. TS of 20 pyrano[4,3-b]chromones was correlated with 3D structure, polarity, ionic potential and electric state. CONCLUSION: Chemical modification of 16 may be a potential choice for designing a new type of anticancer drug.

Quantitative Structure-Cytotoxicity Relationship of 3-(N-Cyclicamino)chromone Derivatives.

BACKGROUND/AIM: 4H-1-Benzopyran-4-ones (chromones) provide a backbone structure for the chemical synthesis of potent anticancer drugs. In contrast to 2-(N-cyclicamino)chromones, the biological activity of 3-(N-cyclicamino)chromones has not been reported. In this study, cytotoxicity of 15 3-(N-cyclicamino)chromone derivatives was investigated and subjected to quantitative structure-activity relationship (QSAR) analysis. MATERIALS AND METHODS: Cytotoxicity against four human oral squamous cell carcinoma cell lines and three oral normal mesenchymal cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor-specificity (TS) was evaluated as the ratio of mean 50% cytotoxic concentration (CC50) against normal oral cells to that against human oral squamous cell carcinoma cell lines. Potency-selectivity expression (PSE) value was calculated by dividing the TS value by the CC50 against tumor cells. Apoptosis induction was evaluated by morphological observation, western blot analysis and cell-cycle analysis. For QSAR analysis, a total of 3,096 physicochemical, structural and quantum chemical features were calculated from the most stabilized structure optimized using CORINA. RESULTS: 3-(4-phenyl-1-piperazinyl)-4H-1-benzopyran-4-one (3a) had the highest tumor specificity, comparable with that of melphalan, without induction of apoptosis. Compound 3a caused cytostatic growth inhibition and had much lower cytotoxicity against human oral keratinocytes compared to doxorubicin. TS of the 15 3-(N-cyclicamino)chromones was correlated with 3D structure and lipophilicity. CONCLUSION: Chemical modification of 3a may be a potential choice for designing a new type of anticancer drug.

Quantitative Structure-Cytotoxicity Relationship of 2-(N-cyclicamino)chromone Derivatives.

BACKGROUND/AIM: 4H-1-Benzopyran-4-ones (chromones) have provided backbone structure for the chemical synthesis of potent anticancer drugs. In this study, the cytotoxicity of fifteen 2-(N-cyclicamino)chromone derivatives was investigated and subjected to quantitative structure-activity relationship (QSAR) analysis. MATERIALS AND METHODS: Cytotoxicity against four human oral squamous cell carcinoma cell lines and three oral normal mesenchymal cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor specificity (TS) was evaluated by ratio of mean 50% cytotoxic concentration (CC50) against normal oral cells to that against human oral squamous cell carcinoma cell lines. Potency-selectivity expression (PSE) value was calculated by dividing the TS value by CC50 against tumor cells. Apoptosis induction was evaluated by morphological observation, western blot analysis and cell-cycle analysis. For QSAR analysis, a total of 3,089 physicochemicals, structural and quantum chemical features were calculated from the most stabilized structure optimized using Corina. RESULTS: 7-Methoxy-2-(4-morpholinyl)-4H-1-benzopyran-4-one (5c) showed highest tumor-specificity, comparable with that of doxorubicin, without inducing apoptosis. Tumor-specificity of fifteen 2-(N-cyclicamino) chromones was correlated with molecular shape, especially 3D-structure. CONCLUSION: Chemical modification of 5c may be a potential choice for designing a new type of anticancer drugs.

Conservative Treatment for Idiopathic Adrenal Hemorrhage Tracked by a Long-term Series of CT Images.

A 55-year-old man was transported to our hospital after a sudden onset of left lower abdominal pain while driving. Computed tomography (CT) of the abdominal region revealed an extensive iso-intense signal region that had a maximum area of 14×15 cm, which we treated conservatively. A series of follow-up CT images showed the gradual decrease of the left peritoneal mass, while continuity with the left adrenal gland became apparent. He was diagnosed with idiopathic adrenal hemorrhage. Adrenal hemorrhage presenting with huge retroperitoneal tumors is rare, and most cases are treated surgically. Therefore, CT images with conservative treatment are rare, holding both clinical interest and significance.

Characterization of the Adverse Effects Induced by Acetaminophen and Nonsteroidal Anti-Inflammatory Drugs Based on the Analysis of the Japanese Adverse Drug Event Report Database.

OBJECTIVES: Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are antipyretic analgesics with established adverse effects (AEs); however, only a few studies have compared their AEs simultaneously. We aimed to compare the AEs of these medications to confirm the respective frequencies of both rare and major AEs. METHODS: We used a high-quality database for spontaneous adverse drug event reporting in Japan. Data were extracted regarding the AEs of acetaminophen and NSAIDs to compare the tendency of the appearance of those AEs between the drugs. We also performed a principal component analysis using the AE data to assess the characteristics of major AEs. RESULTS: Cutaneous disorders and hepatic disorders were the most common AEs induced by acetaminophen and NSAIDs, with gastrointestinal tract disorders also common with NSAID use. Principal component analysis quantitatively showed the tendencies of specific AEs, and it helped demonstrate the characteristics of AEs. Acetaminophen and NSAIDs showed different tendencies in the occurrence of AEs. Each NSAID was plotted based on the tendency of the appearance of major AEs, and AEs were classified by their likelihood of being pharmacological or idiosyncratic. CONCLUSIONS: These findings may help clinicians select an appropriate drug for patients considering their backgrounds, instead of choosing merely based on the class of the drug, for example, cyclooxygenase selectivity. This selection, based on the characteristic information on AEs occurring in clinical settings, might be more suitable for patients.

Osmotic demyelination syndrome complicating diabetes with anti-glutamic acid decarboxylase antibodies and Graves' disease: A case report.

ODS associated with hyperglycemia is rare, with few reports.Immune responses have been recently reported as a mechanism of ODS onset. In the present case, an autoimmune predisposition may have contributed to ODS pathogenesis.