Alzheimer's disease, the most common cause of dementia, is characterized by two major pathological hallmarks: amyloid plaques and neurofibrillary tangles. Based on these two indicators, an amyloid cascade hypothesis was proposed, and accordingly, most current therapeutic approaches are now focused on the removal of beta-amyloid peptides (Abeta from the brain. Additionally, strategies for blocking tau hyperphosphorylation and aggregation have been suggested, including the development of drugs that can block the formation of tangles. However, there are no true disease-modifying drugs in the current market, though many drugs based on theories other than Abeta and tau pathology are under development. The purpose of this review was to provide information on the current development of AD drugs and to discuss the issues related to drug development.
Alzheimer Disease ; Amyloid ; Brain ; Dementia ; Neurofibrillary Tangles ; Peptides ; Plaque, Amyloid

It is uncommon that anesthesiologists experience patients with thyroid storms. In our case, the patient had been medicated for 5 years, however, she developed agranulocytosis. Anti-thyroid drugs were stopped and hyperthyroidism progressed. Her symptoms and laboratory results revealed manifestation of thyroid storm: TSH of < 0.005 IU/L, free T4 of > 7.77 ng/dl, T3 of 403.1 ng/dl, and T4 of 22.15 microg/dl. The euthyroid state had not been achieved before the surgery. From the judgment of difficulty controls of hyperthyroidism, the surgeon requested for an emergency operation. We report a case of total intravenous anesthesia with propofol and remifentanil which achieved hemodynamic stability.
Agranulocytosis ; Anesthesia, Intravenous* ; Emergencies ; Hemodynamics ; Humans ; Hyperthyroidism ; Judgment ; Propofol ; Thyroid Crisis ; Thyrotoxicosis*

BACKGROUND: The size and depth of the double-lumen tube (DLT) are important for one-lung ventilation (OLV). In patients of a short stature, it is difficult to perform OLV successfully. We designed this study to evaluate the dimensions and margin of safety of the left main bronchi in patients of a short stature for appropriate OLV. METHODS: Chest computed tomography (CT) scans of 241 patients (22 male, 219 female) of a short stature (height below 155 cm) were analyzed retrospectively. The diameters of the trachea (DT), the right and left main bronchi (DR and DL), and the lengths of the right and left main bronchi (LR and LL) were measured at the coronal section of the chest CT scans using a picture archiving communication system program. RESULTS: There were no significant correlations between the heights and lengths of the right and left main bronchi. In addition, the ages and weights of the patients showed no significant correlations with the airway dimensions. The lengths of the bronchial lumen of the left-sided Mallinckrodt DLT show variations of 3 to 5.5 mm with tubes of identical sizes. The margin of safety is 13.8 +/- 4.1 mm assuming that appropriately sized DLTs are inserted. CONCLUSIONS: For successful and safe OLV in patients of a short stature, anesthesiologists should consider the length of the main bronchus and the actual length of the bronchial lumen of the DLT.
Body Height ; Bronchi ; Humans ; Male ; One-Lung Ventilation ; Retrospective Studies ; Thorax ; Tomography, X-Ray Computed ; Trachea ; Weights and Measures

Herpes zoster is caused by the reactivation of the varicella-zoster virus, and it typically presents as single dermatomal rash and vesicles. It can cause postherpetic neuralgia as a common complication. In immunocompromised patients, the lesions can be cutaneous, disseminated into two non-contiguous dermatomes, and this entity is referred to as herpes zoster duplex unilateralis or bilateralis. We present a case of postherpetic neuralgia after herpes zoster duplex bilateralis in a 60-year-old immunocompromised man. He had a past history of acute lymphocytic leukemia and was treated with allogeneic peripheral blood stem cell transplantation 1 year before herpes zoster reactivation. His postherpetic neuralgia pain was difficult to treat and it was refractory to conservative medication and neuraxial block.
Exanthema ; Herpes Zoster* ; Herpesvirus 3, Human ; Humans ; Immunocompromised Host* ; Middle Aged ; Neuralgia, Postherpetic* ; Peripheral Blood Stem Cell Transplantation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma

BACKGROUND: Hypothermia is a common physiological condition that occurs during surgical operations. The goal of this experiment is to measure the temperature of the fluids flowing through heated breathing circuits with respect to changes in infusion speed. METHODS: The infusion pump was connected to the intravenous inlet of a heated breathing circuit with two 50 cm extension lines connected to the outlet. Fluids were injected through the heated breathing circuit at 100, 200, 300, 400, 500, 600, and 700 ml/h, with measurement of the fluid temperature immediately after transit (OP 20), 70 cm after transit (OP 70), and 120 cm after transit (OP 120). RESULTS: The mean fluid temperatures at OP 20, OP 70, and OP 120 were 40.7 ± 4.8℃, 35.1 ± 3.22℃, and 31.7 ± 2.5℃, respectively. CONCLUSIONS: The heated breathing circuit was effective to heat the fluid. After passing out the heated breathing circuit, the temperature of the fluid continuously reduced. A length of 70 cm can be used to efficiently supply heated fluid to the patient. From this experiment, it is expected that supplying heated fluid to a patient using the heated breathing circuit will help maintain the patient's body temperature.
Anesthesia ; Bays ; Body Temperature ; Heating* ; Hot Temperature* ; Humans ; Hypothermia ; Infusion Pumps ; Respiration*

BACKGROUND: The aim of this study was to investigate the prevalence of obesity in Korean men with Klinefelter syndrome (KS) and the associated risk factors for obesity and hyperglycemia. METHODS: Data were collected retrospectively from medical records from 11 university hospitals in Korea between 1994 and 2014. Subjects aged ≥18 years with newly diagnosed KS were enrolled. The following parameters were recorded at baseline before treatment: chief complaint, height, weight, fasting glucose level, lipid panel, blood pressure, testosterone, luteinizing hormone, follicle-stimulating hormone, karyotyping patterns, and history of hypertension, diabetes, and dyslipidemia. RESULTS: Data were analyzed from 376 of 544 initially enrolled patients. The rate of the 47 XXY chromosomal pattern was 94.1%. The prevalence of obesity (body mass index ≥25 kg/m²) in Korean men with KS was 42.6%. The testosterone level was an independent risk factor for obesity and hyperglycemia. CONCLUSION: Obesity is common in Korean men with KS. Hypogonadism in patients with KS was associated with obesity and hyperglycemia.
Blood Pressure ; Dyslipidemias ; Fasting ; Follicle Stimulating Hormone ; Glucose ; Hospitals, University ; Humans ; Hyperglycemia* ; Hypertension ; Hypogonadism ; Karyotyping ; Klinefelter Syndrome* ; Korea ; Luteinizing Hormone ; Male ; Medical Records ; Obesity* ; Prevalence ; Retrospective Studies ; Risk Factors ; Testosterone

Heme oxygenase-1-derived carbon monoxide prevents inflammatory vascular disorders. To date, there is no clear evidence that HO-1/CO prevents endothelial dysfunction associated with the downregulation of endothelial NO synthesis in human endothelial cells stimulated with TNF-α. Here, we found that the CO-releasing compound CORM-2 prevented TNF-α-mediated decreases in eNOS expression and NO/cGMP production, without affecting eNOS promoter activity, by maintaining the functional activity of the eNOS mRNA 3′-untranslated region. By contrast, CORM-2 inhibited MIR155HG expression and miR-155-5p biogenesis in TNF-α-stimulated endothelial cells, resulting in recovery of the 3′-UTR activity of eNOS mRNA, a target of miR-155-5p. The beneficial effect of CORM-2 was blocked by an NF-κB inhibitor, a miR-155-5p mimic, a HO-1 inhibitor and siRNA against HO-1, indicating that CO rescues TNF-α-induced eNOS downregulation through NF-κB-responsive miR-155-5p expression via HO-1 induction; similar protective effects of ectopic HO-1 expression and bilirubin were observed in endothelial cells treated with TNF-α. Moreover, heme degradation products, except iron and N-acetylcysteine prevented H₂O₂-mediated miR-155-5p biogenesis and eNOS downregulation. These data demonstrate that CO prevents TNF-α-mediated eNOS downregulation by inhibiting redox-sensitive miR-155-5p biogenesis through a positive forward circuit between CO and HO-1 induction. This circuit may play an important preventive role in inflammatory endothelial dysfunction associated with human vascular diseases.
Acetylcysteine ; Bilirubin ; Carbon Monoxide* ; Carbon* ; Down-Regulation* ; Endothelial Cells ; Heme ; Humans ; Iron ; RNA, Messenger ; RNA, Small Interfering ; Vascular Diseases

Acromegaly is generally caused by a benign growth hormone (GH)-secreting pituitary adenoma. It is characterized by a wide range of complications; cardiovascular, respiratory, bone and joint, and metabolic complications. Among them, impaired glucose tolerance and diabetes mellitus, due to GH-induced insulin resistance, has been reported in approximately 16-46% and 19-56%. They are usually improved following the treatment of acromegaly, surgical or medical therapy. We report a first case of 36-year-old man who was paradoxically diagnosed with GAD antibody positive latent autoimmune diabetes in adults (LADA) after the surgical cure of acromegaly.
Acromegaly ; Adult ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2 ; Glucose ; Growth Hormone ; Humans ; Insulin Resistance ; Joints ; Pituitary Neoplasms

Vascular endothelial growth factor (VEGF) plays a pivotal role in pathologic ocular neovascularization and vascular leakage via activation of VEGF receptor 2 (VEGFR2). This study was undertaken to evaluate the therapeutic mechanisms and effects of the tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a VEGFR2 inhibitor, in the development of vascular permeability and choroidal neovascularization (CNV). In cultured human retinal microvascular endothelial cells (HRMECs), treatment with RLYE blocked VEGF-A-induced phosphorylation of VEGFR2, Akt, ERK, and endothelial nitric oxide synthase (eNOS), leading to suppression of VEGF-A-mediated hyper-production of NO. Treatment with RLYE also inhibited VEGF-A-stimulated angiogenic processes (migration, proliferation, and tube formation) and the hyperpermeability of HRMECs, in addition to attenuating VEGF-A-induced angiogenesis and vascular permeability in mice. The anti-vascular permeability activity of RLYE was correlated with enhanced stability and positioning of the junction proteins VE-cadherin, β-catenin, claudin-5, and ZO-1, critical components of the cortical actin ring structure and retinal endothelial barrier, at the boundary between HRMECs stimulated with VEGF-A. Furthermore, intravitreally injected RLYE bound to retinal microvascular endothelium and inhibited laser-induced CNV in mice. These findings suggest that RLYE has potential as a therapeutic drug for the treatment of CNV by preventing VEGFR2-mediated vascular leakage and angiogenesis.
Actins ; Animals ; Capillary Permeability ; Choroid ; Choroidal Neovascularization ; Claudin-5 ; Endothelial Cells ; Endothelium ; Humans ; Macular Degeneration ; Mice ; Nitric Oxide Synthase Type III ; Permeability ; Phosphorylation ; Receptors, Vascular Endothelial Growth Factor ; Retinaldehyde ; Vascular Endothelial Growth Factor A