Takotsubo Cardiomyopathy: A Case of Persistent Apical Ballooning Complicated by an Apical Mural Thrombus

Takotsubo cardiomyopathy (TTC) is an infrequent cardiac syndrome characterized by acute onset chest pain with apical ballooning on echocardiography. It is often triggered by severe emotional or physical stress, and in contrast to acute myocardial infarction (AMI), the regional wall motion abnormality returns to normal within days. Here, we describe a 62-year-old female who presented with acute onset chest pain during treatment for a liver abscess. We presumed a diagnosis of AMI because of ST segment elevation on electrocardiography and elevated cardiac enzyme levels. However, the patient's coronary arteries were normal on angiography, and apical ballooning was seen on echocardiography. A diagnosis of TTC was made, and the patient was managed with intensive cardiopulmonary support using vasopressors in our hospital's medical intensive care unit. The patient's symptoms improved, but persistent severe left ventricular dysfunction was detected on follow-up echocardiography. After 5 weeks, a new apical mural thrombus appeared, and anticoagulation therapy was started. The apical ballooning persisted 3 months later, although the patient's overall ejection fraction was slightly improved. The apical thrombus was completely resolved without any embolic event. Non-adrenergic inotropics can be recommended in TTC with shock, and clinicians should keep in mind the potential risk of thrombus formation and cardioembolism

Establishment of an experimental model of ovalbumin-induced atopic dermatitis in canines

IntroductionA reliable standard model is required to evaluate the efficacy of new drugs for companion animals, especially dogs. Canine atopic dermatitis (cAD), also known as allergic inflammatory skin disease, is a common condition. Currently, the house dust mite animal model is used in the research of cAD; however, this model exhibits significant individual variation and is difficult to standardize. In this study, we used ovalbumin as an antigen to sensitize and stimulate dogs, thereby establishing a stable model mimicking the T-helper 2 (Th2) response seen in cAD. Our objective was to create a cAD model that could be employed to evaluate the efficacy of novel drugs and mimic the Th2 dominant allergic response observed in the pathogenesis of atopic dermatitis of dogs.MethodsIn this study, six beagles were used. Normal saline was applied to two animals, and ovalbumin to four, on their dorsal skin.ResultsThe ovalbumin-treated groups exhibited clinical cAD symptoms, such as pruritus and erythema. Moreover, plasma levels of the cAD markers immunoglobulin E and CCL17 chemokine were higher in the ovalbumin-treated group than in the vehicle control group. The skin thickness of the epidermis was significantly increased in the ovalbumin-treated group, with infiltration of inflammatory cells observed in the thickened dermis region. In conclusion, treatment of canine skin with an optimal concentration of ovalbumin induced typical cAD-like symptoms, and histological and molecular analyses confirmed an enhanced Th2-related immune response.ConclusionTherefore, we successfully established a suitable Th2-dominant response mimicking cAD, which will facilitate targeted research of atopic dermatitis in dogs

Safe and cost-effective method for application of liquid ethyl formate (FumateTM) as a methyl bromide alternative for perishable commodities: Poster

The cylinderized liquid ethyl formate (EF) formulated with CO2 is one of the great potential fumigants to replace methyl bromide (MeBr) for fresh fruit. However, it is too expensive to adapt commercial practices, and also involves work place safety issue including handling of heavy cylinders as well as restrict emission of CO2, particularly for use in large scale commercial fumigationw. Therefore, it is urgently needed to develop environmental friendly, safe for workers and cost-effective alternative method for application of liquid ethyl formate as a MeBr alternative for perishable commodities. Recently, the environmentally friendly, cost-effective and practically safe use of liquid EF (FumateTM, registered name) with nitrogen gas has been developed and commercialized in Republic of Korea and Australia. The new technology for application of liquid EF is 100 times safer than MeBr in terms of threshold values (EF, TLV = 100 ppm). Ethyl formate is known as food additive and naturally occurred substances as well as a non-ozone depletion chemical. In this report, we demonstrate the liquid EF application technology that offers a clean environment (no ozone depletions and CO2 emissions), safe to fumigators and related workers and practically cost-effective technology to fumigation industry.The cylinderized liquid ethyl formate (EF) formulated with CO2 is one of the great potential fumigants to replace methyl bromide (MeBr) for fresh fruit. However, it is too expensive to adapt commercial practices, and also involves work place safety issue including handling of heavy cylinders as well as restrict emission of CO2, particularly for use in large scale commercial fumigationw. Therefore, it is urgently needed to develop environmental friendly, safe for workers and cost-effective alternative method for application of liquid ethyl formate as a MeBr alternative for perishable commodities. Recently, the environmentally friendly, cost-effective and practically safe use of liquid EF (FumateTM, registered name) with nitrogen gas has been developed and commercialized in Republic of Korea and Australia. The new technology for application of liquid EF is 100 times safer than MeBr in terms of threshold values (EF, TLV = 100 ppm). Ethyl formate is known as food additive and naturally occurred substances as well as a non-ozone depletion chemical. In this report, we demonstrate the liquid EF application technology that offers a clean environment (no ozone depletions and CO2 emissions), safe to fumigators and related workers and practically cost-effective technology to fumigation industry

Safe and high efficient method for application of liquid ethyl formate (FumateTM) to replace methyl bromide for treatment of imported nursery plants: Poster

There have been significantly increased reports of finding invasive quarantine pests with increasing import plants into Korea. Moreover, the efficacy and work safety issues have been reported regarding use of methyl bromide (MeBr) for fumigation of imported nursery plants. For replacement of MeBr use on imported plants, a new technology of using liquid ethyl formate has been registered in South Korea as FumateTM. The technology involved to mix ethyl format with nitrogen gas to form non-flamable ethyl format formulation. It has been evaluated on various imported plants. The FumateTM is recently developed and commercialized in Republic of Korea and Australia for quarantine treatments on fresh fruits, grains etc. Fumigation with FumateTM offers environmental-friendly and practically safe use of liquid ethyl formate. We have extended the use of liquid EF application technology to quarantine treatment of imported nursery plants.There have been significantly increased reports of finding invasive quarantine pests with increasing import plants into Korea. Moreover, the efficacy and work safety issues have been reported regarding use of methyl bromide (MeBr) for fumigation of imported nursery plants. For replacement of MeBr use on imported plants, a new technology of using liquid ethyl formate has been registered in South Korea as FumateTM. The technology involved to mix ethyl format with nitrogen gas to form non-flamable ethyl format formulation. It has been evaluated on various imported plants. The FumateTM is recently developed and commercialized in Republic of Korea and Australia for quarantine treatments on fresh fruits, grains etc. Fumigation with FumateTM offers environmental-friendly and practically safe use of liquid ethyl formate. We have extended the use of liquid EF application technology to quarantine treatment of imported nursery plants

Effect of BMP-2 Delivery Mode on Osteogenic Differentiation of Stem Cells

Differentiation of stem cells is an important strategy for regeneration of defective tissue in stem cell therapy. Bone morphogenetic protein-2 (BMP-2) is a well-known osteogenic differentiation factor that stimulates stem cell signaling pathways by activating transmembrane type I and type II receptors. However, BMPs have a very short half-life and may rapidly lose their bioactivity. Thus, a BMP delivery system is required to take advantage of an osteoinductive effect for osteogenic differentiation. Previously, BMP delivery has been designed and evaluated for osteogenic differentiation, focusing on carriers and sustained release system for delivery of BMPs. The effect of the delivery mode in cell culture plate on osteogenic differentiation potential was not evaluated. Herein, to investigate the effect of delivery mode on osteogenic differentiation of BM-MSCs in this study, we fabricated bottom-up release and top-down release systems for culture plate delivery of BMP-2. And also, we selected Arg-Gly-Asp- (RGD-) conjugated alginate hydrogel for BMP-2 delivery because alginate is able to release BMP-2 in a sustained manner and it is a biocompatible material. After 7 days of culture, the bottom-up release system in culture plate significantly stimulated alkaline phosphate activity of human bone marrow-mesenchymal stem cells. The present study highlights the potential value of the tool in stem cell therapy

Protection of nigral dopaminergic neurons by AAV1 transduction with Rheb(S16H) against neurotoxic inflammation in vivo

We recently reported that adeno-associated virus serotype 1 (AAV1) transduction of murine nigral dopaminergic (DA) neurons with constitutively active ras homolog enriched in brain with a mutation of serine to histidine at position 16 [Rheb(S16H)] induced the production of neurotrophic factors, resulting in neuroprotective effects on the nigrostriatal DA system in animal models of Parkinson's disease (PD). To further investigate whether AAV1-Rheb(S16H) transduction has neuroprotective potential against neurotoxic inflammation, which is known to be a potential event related to PD pathogenesis, we examined the effects of Rheb(S16H) expression in nigral DA neurons under a neurotoxic inflammatory environment induced by the endogenous microglial activator prothrombin kringle-2 (pKr-2). Our observations showed that Rheb(S16H) transduction played a role in the neuroprotection of the nigrostriatal DA system against pKr-2-induced neurotoxic inflammation, even though there were similar levels of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta), in the AAV1-Rheb(S16H)-treated substantia nigra (SN) compared to the SN treated with pKr-2 alone; the neuroprotective effects may be mediated by the activation of neurotrophic signaling pathways following Rheb(S16H) transduction of nigral DA neurons. We conclude that AAV1-Rheb(S16H) transduction of neuronal populations to activate the production of neurotrophic factors and intracellular neurotrophic signaling pathways may offer promise for protecting adult neurons from extracellular neurotoxic inflammation.1

Neurotrophic interactions between neurons and astrocytes following AAV1-Rheb(S16H) transduction in the hippocampus in vivo

Background and Purpose: We recently reported that AAV1-Rheb(S16H) transduction could protect hippocampal neurons through the induction of brain-derived neurotrophic factor (BDNF) in the rat hippocampus in vivo. It is still unclear how neuronal BDNF produced by AAV1-Rheb(S16H) transduction induces neuroprotective effects in the hippocampus and whether its up-regulation contributes to the enhance of a neuroprotective system in the adult brain. Experimental Approach: To determine the presence of a neuroprotective system in the hippocampus of patients with Alzheimer's disease (AD), we examined the levels of glial fibrillary acidic protein, BDNF and ciliary neurotrophic factor (CNTF) and their receptors, tropomyocin receptor kinase B (TrkB) and CNTF receptor α(CNTFRα), in the hippocampus of AD patients. We also determined whether AAV1-Rheb(S16H) transduction stimulates astroglial activation and whether reactive astrocytes contribute to neuroprotection in models of hippocampal neurotoxicity in vivo and in vitro. Key Results: AD patients may have a potential neuroprotective system, demonstrated by increased levels of full-length TrkB and CNTFRα in the hippocampus. Further AAV1-Rheb(S16H) transduction induced sustained increases in the levels of full-length TrkB and CNTFRα in reactive astrocytes and hippocampal neurons. Moreover, neuronal BDNF produced by Rheb(S16H) transduction of hippocampal neurons induced reactive astrocytes, resulting in CNTF production through the activation of astrocytic TrkB and the up-regulation of neuronal BDNF and astrocytic CNTF which had synergistic effects on the survival of hippocampal neurons in vivo. Conclusions and Implications: The results demonstrated that Rheb(S16H) transduction of hippocampal neurons could strengthen the neuroprotective system and this intensified system may have a therapeutic value against neurodegeneration in the adult brain. © 2019 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society1

Increased Risk of Progression of Coronary Artery Calcification in Male Subjects with High Baseline Waist-to-Height Ratio: The Kangbuk Samsung Health Study

BackgroundThe waist-to-height ratio (WHtR) is an easy and inexpensive adiposity index that reflects central obesity. In this study, we examined the association of baseline WHtR and progression of coronary artery calcification (CAC) over 4 years of follow-up in apparently healthy Korean men.MethodsA total of 1,048 male participants (mean age, 40.9 years) in a health-screening program in Kangbuk Samsung Hospital, Seoul, Korea who repeated a medical check-up in 2010 and 2014 were recruited. Baseline WHtR was calculated using the value for the waist in 2010 divided by the value for height in 2010. The CAC score (CACS) of each subject was measured by multi-detector computed tomography in both 2010 and 2014. Progression of CAC was defined as a CACS change over 4 years greater than 0.ResultsDuring the follow-up period, progression of CAC occurred in 278 subjects (26.5%). The subjects with CAC progression had slightly higher but significant baseline WHtR compared to those who did not show CAC progression (0.51±0.04 vs. 0.50±0.04, P<0.01). The proportion of subjects with CAC progression significantly increased as the baseline WHtR increased from the 1st quartile to 4th quartile groups (18.3%, 18.7%, 28.8%, and 34.2%; P<0.01). The risk for CAC progression was elevated with an odds ratio of 1.602 in the 4th quartile group of baseline WHtR even after adjustment for confounding variables (95% confidence interval, 1.040 to 2.466).ConclusionIncreased baseline WHtR was associated with increased risk for CAC progression. WHtR might be a useful screening tool to identify individuals at high risk for subclinical atherosclerosis