Simultaneous hypersensitivity reactions to trimethoprim-sulfamethoxazole and amoxicillin-clavulanate in a dog.

Antibiotics are known to be able to cause hypersensitivity reactions through various mechanisms. We present a case of drug-induced immune thrombocytopenia (DITP) and anaphylactic shock occurring simultaneously in a dog after the administration of two classes of antibiotics, namely trimethoprim-sulfamethoxazole (TMP-SMX) and amoxicillin-clavulanate (AMC). The patient recovered completely from DITP on discontinuation of TMP-SMX and the anaphylactic shock caused by AMC was treated with intensive care. DITP is a rare adverse drug reaction (ADR), and anaphylactic shock is a life-threatening ADR. This is the first case report of a dog manifesting two types of hypersensitivity reactions caused by two antibiotics.

Non-Targeted Metabolomics Approach Revealed Significant Changes in Metabolic Pathways in Patients with Chronic Traumatic Encephalopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is frequently found in athletes and those who have experienced repetitive head traumas. CTE is associated with a variety of neuropathologies, which cause cognitive and behavioral impairments in CTE patients. However, currently, CTE can only be diagnosed after death via brain autopsy, and it is challenging to distinguish it from other neurodegenerative diseases with similar clinical features. To better understand this multifaceted disease and identify metabolic differences in the postmortem brain tissues of CTE patients and control subjects, we performed ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS)-based non-targeted metabolomics. Through multivariate and pathway analysis, we found that the brains of CTE patients had significant changes in the metabolites involved in astrocyte activation, phenylalanine, and tyrosine metabolism. The unique metabolic characteristics of CTE identified in this study were associated with cognitive dysfunction, amyloid-beta deposition, and neuroinflammation. Altogether, this study provided new insights into the pathogenesis of CTE and suggested appealing targets for both diagnosis and treatment for the disease.

Anti-Inflammatory and Immune Modulatory Effects of Synbio-Glucan in an Atopic Dermatitis Mouse Model.

Many trials have been conducted to treat atopic dermatitis (AD), but these therapies are generally unsuccessful because of their insufficiency or side effects. This study examined the efficacy of ß-glucan derived from oats with fermented probiotics (called Synbio-glucan) on an AD-induced mouse model. For the experiment, Nc/Nga mice were exposed to a house dust mite extract (HDM) to induce AD. The mice were placed in one of four groups: positive control group, Synbio-glucan topical treatment group, Synbio-glucan dietary treatment group, and Synbio-glucan topical + dietary treatment group. The experiment revealed no significant difference in the serum IgE concentration among the groups. Serum cytokine antibody arrays showed that genes related to the immune response were enriched. A significant difference in the skin lesion scores was observed between the groups. Compared to the control group tissue, skin lesions were alleviated in the Synbio-glucan topical treatment group and Synbio-glucan dietary treatment group. Interestingly, almost normal structures were observed within the skin lesions in the Synbio-glucan topical + dietary treatment group. Overall, the ß-glucan extracted from oats and fermented probiotic mixture is effective in treating atopic dermatitis.

Serum Concentration of Inflammatory Cytokines in Dogs with Suspected Acute Pancreatitis.

Acute pancreatitis is an acute inflammatory process in the pancreas that is common in dogs. This study was designed to compare cytokines between healthy dogs and dogs with suspected acute pancreatitis. For the canine cytokine antibody array, three healthy dogs and three dogs with suspected acute pancreatitis were included. Interleukin (IL)-2, IL-6, IL-10, GM-CSF, and TNF-α were not detected in either group based on the results. Conversely, IL-8 (p = 0.035), Monocyte Chemoattractant Protein-1 (MCP)-1 (p = 0.0138), Receptor for Advanced Glycation Endproducts (RAGE) (p = 0.0079), and stem cell factor (SCF) (p = 0.034) were significantly increased in dogs with suspected acute pancreatitis. However, vascular endothelial growth factor (VEGF) (p = 0.6971) did not differ significantly between groups. For the canine serum Enzyme-Linked Immunosorbent Assay (ELISA), eight healthy dogs and eight dogs with suspected acute pancreatitis were included. ELISA revealed that IL-8 (p < 0.0001), MCP-1 (p < 0.0001), RAGE (p = 0.006), and SCF (p = 0.0002) were all significantly upregulated in the experimental group. We confirmed multiple patterns of cytokines in suspected acute pancreatitis of dogs via canine cytokine antibody array using a small quantity of serum. After this procedure, we reevaluated the cytokines, which were significantly increased in dogs with suspected acute pancreatitis, by ELISA, with more samples. Through this study, we confirmed that MCP-1, RAGE, and SCF were newly suggested factors in dogs with suspected acute pancreatitis.

The risk of hip fractures in individuals over 50 years old with prediabetes and type 2 diabetes - A longitudinal nationwide population-based study.

BACKGROUND: The present study aimed to investigate the association between type 2 diabetes mellitus (T2DM) and hip fractures using a large-scale nationwide population-based cohort that is representative of the Republic of Korea. We determined the risks of hip fractures in individuals with prediabetes and T2DM with different diabetes durations, and compared them with the risks of hip fractures in individuals without T2DM. METHODS: A total of 5,761,785 subjects over 50 years old who underwent the National Health Insurance Service medical checkup in 2009-2010 were included. Subjects were classified into 5 groups based on the diabetes status; Normal, Prediabetes, Newly-diagnosed T2DM, T2DM less than 5 years, and T2DM more than 5 years. They were followed from the date of the medical checkup to the end of 2016. The endpoint was a new development of hip fracture during follow-up. The hazard ratios (HRs) and 95% confidence intervals (CIs) of hip fractures for each group were analyzed using Cox proportional hazard regression models after adjusting for age, sex, smoking, alcohol drinking, regular exercise, body mass index, hypertension, dyslipidemia, and chronic kidney disease. RESULTS: The HRs of hip fractures were 1 in the Normal group, 1.032 (95% CI: 1.009, 1.056) in the Prediabetes group, 1.168 (95% CI: 1.113, 1.225) in the Newly-diagnosed T2DM2, 1.543 (95% CI: 1.495, 1.592) in the T2DM less than 5 years and 2.105 (95% CI: 2.054, 2.157) in the T2DM more than 5 years. The secular trend of the HRs of hip fractures according to the duration of T2DM was statistically significant (P < .001). Subgroup analyses also showed the same increasing pattern of the HRs of hip fractures according to the duration of T2DM in both sexes and all age groups (50-64 years, 65-74 years, over 75 years). CONCLUSIONS: In summary, this large-scale, retrospective, longitudinal, nationwide population-based cohort study of 5,761,785 subjects demonstrated that the risks of hip fractures started to increase in prediabetes and was associated linearly with the duration of T2DM. The secular trend of risks of hip fractures according to the duration of T2DM was consistent in both sexes and all age groups.

Comparison of the presentation of atopic dermatitis induced by trinitrochlorobenzene and house dust mite in NC/Nga mice.

BACKGROUND: Atopic dermatitis (AD) is a common chronic inflammatory skin disease. To understand AD, there have been many trials establishing AD animal models. Although various trials to establish AD animal models have been existed, even the mechanisms of AD in animal models are not enough clarified. OBJECTIVES: This study assessed AD characteristics induced in Nishiki-nezumi Cinnamon/Nagoya (Nc/Nga) mice following trinitrochlorobenzene (TNCB) treatment for different periods and house dust mite (HDM) treatment to compare each model's immunological patterns, especially with cytokine antibody array tool. METHODS: In this study, we exposed Nc/Nga mice to TNCB or HDM extract to induce AD. Nc/Nga mice were divided into 4 groups: control, TNCB 2 weeks-treated, TNCB 8 weeks-treated, and HDM-treated groups. After AD induction, all mice were evaluated by serum immunoglobulin E (IgE) concentration and serum cytokine antibody assays, scoring of skin lesions, scoring of scratching frequency, and histological analysis. RESULTS: The results showed significant differences between groups in serum IgE concentration, skin lesion scores, and scratching frequency. The analysis results for serum cytokine antibody arrays showed that in the TNCB 8 weeks- and HDM-treated groups, but not in the TNCB 2 weeks-treated group, expressions of genes related to the immune response were enriched. Among the histological results, the skin lesions in the HDM-treated group were most similar to those of AD. CONCLUSIONS: We confirmed that immunological pattern of AD mice was markedly different between HDM and TNCB treated groups. In addition, the immunological pattern was quietly different dependent on TNCB treated duration.

Metabolomic Analysis Identifies Alterations of Amino Acid Metabolome Signatures in the Postmortem Brain of Alzheimer's Disease.

Despite significant advances in neuroscience research over the past several decades, the exact cause of AD has not yet fully understood. The metabolic hypothesis as well as the amyloid and tau hypotheses have been proposed to be associated with AD pathogenesis. In order to identify metabolome signatures from the postmortem brains of sporadic AD patients and control subjects, we performed ultra performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometer (UPLC-LTQ-Orbitrap-MS). Not only our study identified new metabolome signatures but also verified previously known metabolome profiles in the brain. Statistical modeling of the analytical data and validation of the structural assignments discovered metabolic biomarkers associated with the AD pathogenesis. Interestingly, hypotaurin, myo-inositol and oxo-proline levels were markedly elevated in AD while lutamate and N-acetyl-aspartate were decreased in the postmortem brain tissue of AD patients. In addition, neurosteroid level such as cortisol was significantly increased in AD. Together, our data indicate that impaired amino acid metabolism is associated with AD pathogenesis and the altered amino acid signatures can be useful diagnostic biomarkers of AD. Thus, modulation of amino acid metabolism may be a possible therapeutic approach to treat AD.

Safety assessment of trans-tympanic photobiomodulation.

We evaluated functional and morphological changes after trans-tympanic laser application using several different powers of photobiomodulation (PBM). The left (L) ears of 17 rats were irradiated for 30 min daily over 14 days using a power density of 909.1 (group A, 5040 J), 1136.4 (group B, 6300 J), and 1363.6 (group C, 7560 J) mW/cm(2). The right (N) ears served as controls. The safety of PBM was determined by endoscopic findings, auditory brainstem response (ABR) thresholds, and histological images of hair cells using confocal microscopy, and light microscopic images of the external auditory canal (EAC) and tympanic membrane (TM). Endoscopic findings revealed severe inflammation in the TM of C group; no other group showed damage in the TM. No significant difference in ABR threshold was found in the PBM-treated groups (excluding the group with TM damage). Confocal microscopy showed no histological difference between the AL and AN, or BL and BN groups. However, light microscopy showed more prominent edema, inflammation, and vascular congestion in the TM of BL ears. This study found a dose-response relationship between laser power parameters and TM changes. These results will be useful for defining future allowance criteria for trans-tympanic laser therapies.

Focal adhesion kinase and Src expression in premalignant and malignant skin lesions.

Focal adhesion kinase (FAK) and Src are non-receptor tyrosine kinases. FAK and Src play a critical role in inducing malignant transformation in tumor cells. We performed immunohistochemical staining for total and phosphorylated forms of FAK and Src, to evaluate the role of FAK and Src in the development of premalignant and malignant skin lesions. A total of 59 facial skin samples (30 actinic keratoses, 10 Bowen's diseases, 13 squamous cell carcinomas and six perilesional skins) were immunohistochemically stained for Ki-67, total (t) and phosphorylated (p) form of FAK and Src. Cells positive for t-Src, p-Src-y530, t-FAK and pFAK-s722 were detected in premalignant intra-epithelial lesions (PELs) and squamous cell carcinomas (SCCs), but not in the perilesional skin. There was a tendency towards high correlation between Ki-67 and t-FAK or pFAK-s722, suggestive of the active role of FAK in cell proliferation. However, our findings of higher t-Src and p-Src-y530 positive cells in PELs, as compared to SCCs (with higher Ki-67 level), are suggestive of the other role of Src in tumor formation and progression, which requires further investigation.

Treatment of nevus of Ota using low fluence Q-switched Nd:YAG laser.

BACKGROUND: Nevus of Ota, caused by dermal melanocytosis, is cosmetically troublesome in Asian patients. The destruction of dermal melanocytosis using Q-switched laser systems carries a high risk of postinflammatory hyperpigmentation/hypopigmentation. METHODS: To determine the usefulness, safety, and adverse problems of low fluence 1064 nm Q-switched Nd:YAG laser in the treatment of nevus of Ota, 19 Korean patients (five male and 14 female; Fitzpatrick skin type IV) who were clinically diagnosed as having nevus of Ota were enrolled in the present study. Low fluence laser treatments were performed with a collimated Q-switched Nd:YAG laser at intervals of two weeks. The fluence of laser treatments was set at 2.5 J/cm(2) and adjusted based on patient response to the previous treatment session and sensitivity to pain. Treatment was applied until the lesions showed mild erythema. RESULTS: The mean number of total treatment sessions was 17.1 (range 6-32). Among the 19 patients, 18 reached near total improvement, while one patient failed to reach near total improvement after 11 treatment sessions. The mean fluence of treatment was 2.5 J/cm(2) (range 2.0-5.0 J/cm(2) ). Five patients complained of delayed eyelid response. Post-therapy hyperpigmentation was observed in one patient. CONCLUSION: Low fluence 1064 nm Q-switched Nd:YAG laser is an effective modality for the treatment of nevus of Ota with a low incidence of side effects. It is an easy to perform treatment with low downtime.

Medial or medio-lateral graft tympanoplasty for repair of tympanic membrane perforation.

OBJECTIVE: To describe and evaluate the medio-lateral graft tympanoplasty(1) for the reconstruction of anterior or subtotal tympanic membrane (TM) perforation and medial graft tympanoplasty for posterior TM perforation. METHODS: Retrospective study of 200 patients who underwent medio-lateral graft tympanoplasty (100 cases) and medial graft tympanoplasty (100 cases) at community and tertiary care medical centers from 1995 to 2006. All patients underwent preoperative and postoperative audiograms. In the medial graft tympanoplasty, the graft is placed entirely medial to the remaining TM and malleus. First, margin of TM perforation is denuded removing ring of squamous tissue. Tympanomeatal flap is elevated. Temporalis fascia is harvested, semidried, and grafted medial to the TM perforation and malleus with Gelfoam packing supporting the graft. In the medio-lateral graft technique, posterior tympanomeatal flap is elevated same as in the medial graft tympanoplasty first. Anterior-medial canal skin is elevated down to the annulus. At the annulus only squamous epithelial layer of TM is elevated up to anterior half of the TM perforation. Temporalis fascia is grafted medial to posterior half of the perforation and lateral to anterior half of the de-epithelialized TM perforation up to the annulus. Anterior canal skin is rotated to cover the fascia graft and TM perforation as a second layer closure. Patients were followed for at least six months. Outcome was considered successful if TM is healed and intact. RESULTS: There were four failures (96% success rate) in medial graft method for posterior TM perforation due to infection and re-perforation. In the medio-lateral graft tympanoplasty, there were three failures (97% success rate) due to a postoperative infection, anterior blunting and recurrent cholesteatoma. CONCLUSION: The medial graft tympanoplasty works well for posterior TM perforation. The medio-lateral graft method is an excellent method for the reconstruction of large anterior or subtotal TM perforation. This new method should help otologic surgeons to improve outcome of tympanoplasty for anterior or subtotal TM perforation.