Neuroinflammation—a common pathological feature of neurodegenerative disorders such as Alzheimer’s disease—is mediated by microglial activation. Thus, inhibiting microglial activation is vital for treating various neurological disorders. 7,3’,4’-Trihydroxyisoflavone (THIF)—a secondary metabolite of the soybean compound daidzein—possesses antioxidant and anticancer properties. However, the effects of 7,3’,4’-THIF on microglial activation have not been explored. In this study, antineuroinflammatory effects of 7,3’,4’-THIF in lipopolysaccharide (LPS)-stimulated BV2 microglial cells were examined. 7,3’,4’-THIF significantly suppressed the production of the proinflammatory mediators nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) as well as of the proinflammatory cytokine interleukin-6 (IL-6) in LPS-stimulated BV2 microglial cells. Moreover, 7,3’,4’-THIF markedly inhibited reactive oxygen species (ROS) generation. Western blotting revealed that 7,3’,4’-THIF diminished LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), glycogen synthase kinase-3β (GSK-3β), and nuclear factor kappa B (NF-κB). Overall, 7,3’,4’-THIF exerts antineuroinflammatory effects against LPSinduced microglial activation by suppressing mitogen-activated protein kinase (MAPK) and NF-κB signaling, ultimately reducing proinflammatory responses. Therefore, these antineuroinflammatory effects of 7,3’,4’-THIF suggest its potential as a therapeutic agent for neurodegenerative disorders.

Alagille syndrome (AGS) is a rare autosomal dominant inherited disorder, with major clinical manifestations of bile duct paucity, cholestasis, cardiovascular anomaly, ophthalmic abnormalities, butterfly vertebrae, and dysmorphic facial appearance. It is caused by heterozygous mutations in JAG1 or NOTCH of the Notch signaling pathway presenting with variable phenotypic penetrance and involving multiple organ systems. The following case report describes a unique case of a 16-year-old female with AGS who presented with the primary complaint of renovascular hypertension. She had a medical history of ventricular septal defect and polycystic ovary syndrome. The patient had a dysmorphic facial appearance including frontal bossing, bulbous tip of the nose, a pointed chin with prognathism, and deeply set eyes with mild hypertelorism. Stenoocclusive changes of both renal arteries, celiac artery, lower part of the abdominal aorta, and left intracranial artery, along with absence of the left internal carotid artery were found on examination. Whole exome sequencing was performed and revealed a pathologic mutation of JAG1, leading to the diagnosis of AGS. Reverse phenotyping detected butterfly vertebrae and normal structure and function of the liver and gallbladder. While the representative symptom of AGS in most scenarios is a hepatic problem, in this case, the presenting clinical features were the vascular anomalies. Clinical manifestations of AGS are diverse, and this case demonstrates that renovascular hypertension might be in some cases a presenting symptom of AGS.

Background: and PurposeImpulse-control disorder is an important nonmotor symptom of Parkinson's disease (PD) that can lead to financial and social problems, and be related to a poor quality of life. A nationwide multicenter prospective study was performed with the aim of validating the Korean Version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (K-QUIP-RS). Methods: The K-QUIP-RS was constructed using forward and backward translation, and pretesting of the prefinal version. PD patients on stable medical condition were recruited from 27 movement-disorder clinics. Participants were assessed using the K-QUIP-RS and evaluated for parkinsonian motor and nonmotor statuses and for PD-related quality of life using a predefined evaluation battery. The test–retest reliability of the K-QUIP-RS was assessed over an interval of 10–14 days, and correlations between the KQUIP-RS and other clinical scales were analyzed. Results: This study enrolled 136 patients. The internal consistency of the K-QUIP-RS was indicated by a Cronbach's α coefficient of 0.846, as was the test–retest reliability by a Guttman split-half coefficient of 0.808. The total K-QUIP-RS score was positively correlated with the scores for depression and motivation items on the Unified PD Rating Scale (UPDRS), Montgomery-Asberg Depression Scale, and Rapid-Eye-Movement Sleep-Behavior-Disorders Questionnaire. The total K-QUIP-RS score was also correlated with the scores on part II of the UPDRS and the PD Quality of Life-39 questionnaire, and the dopaminergic medication dose. Conclusions The K-QUIP-RS appears to be a reliable assessment tool for impulse-control and related behavioral disturbances in the Korean PD population.

Daidzein isolated from soybean (Glycine max) has been widely studied for its antioxidant and anti-inflammatory activities. However, the protective effects of 7,8,4′-trihydroxyisoflavone (THIF), a major metabolite of daidzein, on 6-hydroxydopamine (OHDA)-induced neurotoxicity are not well understood. In the current study, 7,8,4′-THIF significantly inhibited neuronal cell death and lactate dehydrogenase (LDH) release induced by 6-OHDA in SH-SY5Y cells, which were used as an in vitro model of Parkinson's disease (PD). Moreover, pretreatment with 7,8,4′-THIF significantly increased the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) and decreased malondialdehyde (MDA) activity in 6-OHDA-induced SH-SY5Y cells. In addition, 7,8,4′-THIF significantly recovered 6-OHDA-induced cleaved caspase-3, cleaved caspase-9, cleaved poly-ADP-ribose polymerase (PARP), increased Bax, and decreased Bcl-2 levels. Additionally, 7,8,4′-THIF significantly restored the expression levels of phosphorylated c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase 1/2 (ERK 1/2), phosphatidylinositol 3-kinases (PI3K)/Akt, and glycogen synthase kinase-3 beta (GSK-3β) in 6-OHDA-induced SH-SY5Y cells. Further, 7,8,4′-THIF significantly increased the reduced tyrosine hydroxylase (TH) level induced by 6-OHDA in SH-SY5Y cells. Collectively, these results suggest that 7,8,4′-THIF protects against 6-OHDA-induced neuronal cell death in cellular PD models. Also, these effects are mediated partly by inhibiting activation of the MAPK and PI3K/Akt/GSK-3β pathways.
Apoptosis ; Caspase 3 ; Caspase 9 ; Catalase ; Cell Death ; Glutathione ; Glycogen Synthase ; In Vitro Techniques ; JNK Mitogen-Activated Protein Kinases ; L-Lactate Dehydrogenase ; Malondialdehyde ; Neurons ; Oxidopamine ; Parkinson Disease ; Phosphatidylinositol 3-Kinases ; Phosphotransferases ; Protein Kinases ; Soybeans ; Superoxide Dismutase ; Tyrosine 3-Monooxygenase

BACKGROUND AND OBJECTIVES: Ranulas, pseudo cysts found on the floor of mouth, develop from the retention or extravasation of saliva from the sublingual gland. The main treatment of ranula is surgical excision but the extent of surgery is controversial. The aim of this study was to evaluate the significance of sublingual gland excision in the surgical treatment of ranula. SUBJECTS AND METHOD: We retrospectively reviewed 112 patients with ranula who had undergone surgical excision from January 2004 to April 2016. Those who underwent any previous treatment such as sclerotherapy, marsupialization, or excision of cyst were excluded in the study. Surgical outcomes including complications and recurrence were compared between the group that went through simple cyst excision and the group that went through cyst and sublingual gland excision. RESULTS: Of 112 patients, 94 were simple ranula and 18 were plunging ranula. Thirty-seven (33%) were male and 75 (67%) were female. Of the 94 simple ranula patients, 23 underwent excision of cyst only; the remaining 71 patients and all other patients with plunging ranula underwent excision of cyst and sublingual gland together. The recurrence rate was significantly lower for the cyst and sublingual gland excision group than for the simple cyst excision group (2.2% vs. 17.4%, p=0.004). The complication rate did not differ between the two groups (4.3% vs. 1.1%, p=0.298). CONCLUSION: The excision of sublingual glands as well as cysts is an important option to reduce recurrence in the surgical treatment of ranula.
Female ; Humans ; Male ; Methods ; Mouth Floor ; Ranula* ; Recurrence ; Retrospective Studies ; Saliva ; Sclerotherapy ; Sublingual Gland*

BACKGROUND/AIMS: Elevated lipoprotein(a) (Lp[a]) level is known to be a risk factor for cardiovascular disease (CVD). However, the data that has been reported on the association between the Lp(a) level and CVD in type 2 diabetes has been limited and incoherent. The aim of this study was to investigate the relationship between the Lp(a) concentration and new onset CVD in type 2 diabetes. METHODS: From March 2003 to December 2004, patients with type 2 diabetes without a prior history of CVD were consecutively enrolled. CVD was defined as the occurrence of coronary artery disease or ischemic stroke. Cox proportional hazards models were used to identify the associations between the Lp(a) and CVD after adjusting for confounding variables. RESULTS: Of the 1,183 patients who were enrolled, 833 participants were evaluated with a median follow-up time of 11.1 years. A total of 202 participants were diagnosed with CVD (24.2%). The median Lp(a) level for 1st and 4th quartile group was 5.4 (3.5 to 7.1) and 55.7 mg/dL (43.1 to 75.3). Compared with patients without CVD, those with CVD were older, had a longer duration of diabetes and hypertension, and used more insulin and angiotensin converting enzyme inhibitors/angiotensin receptor blockers at baseline. A Cox hazard regression analysis revealed that the development of CVD was significantly associated with serum Lp(a) level (hazard ratio, 1.92; 95% confidence interval [CI], 1.26 to 2.92; p < 0.001, comparing the 4th vs. 1st quartile of Lp[a]). CONCLUSIONS: Elevated Lp(a) level was an independent predictable risk factor for CVD in type 2 diabetes. Other cardiovascular risk factors should be treated more intensively in type 2 diabetic patients with high Lp(a) levels.
Cardiovascular Diseases* ; Cohort Studies* ; Confounding Factors (Epidemiology) ; Coronary Artery Disease ; Diabetes Mellitus, Type 2* ; Follow-Up Studies ; Humans ; Hypertension ; Insulin ; Lipoprotein(a)* ; Peptidyl-Dipeptidase A ; Proportional Hazards Models ; Prospective Studies* ; Risk Factors ; Stroke

PURPOSE: Extracorporeal life support (ECLS) is a term used to describe a number of modalities including extracorporeal membrane oxygenation (ECMO) to support cardiac and/or pulmonary systems. The purpose of this study is to review the available evidence regarding the effect of ECLS in patients with acute poisoning. METHODS: Electronic literature searches with PubMed, Embase, Cochrane library, and KoreaMed were conducted for identification of relevant studies addressing ECLS in treatment of acute poisoning. The literature search was conducted by two investigators in March, 2016 with publication language restricted to English and Korean. The toxic substance, technique of ECLS, and final outcome of each case were analyzed. RESULTS: The final analysis included 64 articles including 55 case reports. There were no articles classified according to a high level of evidence such as randomized trial and prospective cohort study. ECLS treatment was used in the management of patients poisoned with 36 unique substances. Venovenous ECMO was performed in 4 cases. Among the reported cases, 10 patients died despite treatment with ECLS. CONCLUSION: Evidence supporting ECLS for patients with acute poisoning is inadequate. However, many case reports suggest that early consideration of ECLS in poisoned patients with refractory cardiac arrest or hemodynamic compromise refractory to standard therapies may be beneficial.
Cardiopulmonary Bypass ; Cohort Studies ; Extracorporeal Circulation ; Extracorporeal Membrane Oxygenation ; Heart Arrest ; Hemodynamics ; Humans ; Poisoning* ; Prospective Studies ; Publications ; Research Personnel

BACKGROUND: We investigated an association between baseline heart rate-corrected QT (QTc) interval before severe hypoglycemia (SH) and prolongation of QTc interval during SH in patients with type 2 diabetes mellitus (T2DM). METHODS: Between January 2004 and June 2014, 208 patients with T2DM, who visited the emergency department because of SH and underwent standard 12-lead electrocardiography within the 6-month period before SH were consecutively enrolled. The QTc interval was analyzed during the incidence of SH, and 6 months before and after SH. QTc intervals of 450 ms or longer in men and 460 ms or longer in women were considered abnormally prolonged. RESULTS: The mean age and diabetes duration were 68.1±12.1 and 14.1±10.1 years, respectively. The mean QTc intervals at baseline and SH episodes were 433±33 and 460±33 ms, respectively (P<0.001). One hundred and fourteen patients (54.8%) had a prolonged QTc interval during SH. There was a significant decrease in the prolonged QTc interval within 6 months after SH (QTc interval prolongation during SH vs. after recovery, 54.8% vs. 33.8%, P<0.001). The prolonged QTc interval was significantly associated with baseline QTc interval prolongation (odds ratio, 2.92; 95% confidence interval, 1.22 to 6.96; P=0.016) after adjusting for multiple confounders. CONCLUSION: A prolonged QTc interval at baseline was significantly associated with prolongation of the QTc interval during SH in patients with T2DM, suggesting the necessity of QTc interval monitoring and attention to those with a prolonged QTc interval to prevent SH.
Diabetes Mellitus, Type 2* ; Electrocardiography ; Emergency Service, Hospital ; Female ; Heart ; Humans ; Hypoglycemia* ; Incidence ; Male

BACKGROUND: We investigated clinical course and risk factors for diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 759 patients with T2DM without DR were included from January 2001 to December 2004. Retinopathy evaluation was performed at least annually by ophthalmologists. The severity of the DR was classified into five categories according to the International Clinical Diabetic Retinopathy Severity Scales. RESULTS: Of the 759 patients, 523 patients (68.9%) completed the follow-up evaluation. During the follow-up period, 235 patients (44.9%) developed DR, and 32 patients (13.6%) progressed to severe nonproliferative DR (NPDR) or proliferative DR (PDR). The mean duration of diabetes at the first diagnosis of mild NPDR, moderate NPDR, and severe NPDR or PDR were 14.8, 16.7, and 17.3 years, respectively. After adjusting multiple confounding factors, the significant risk factors for the incidence of DR risk in patients with T2DM were old age, longer duration of diabetes, higher mean glycosylated hemoglobin (HbA1c), and albuminuria. Even in the patients who had been diagnosed with diabetes for longer than 10 years at baseline, a decrease in HbA1c led to a significant reduction in the risk of developing DR (hazard ratio, 0.73 per 1% HbA1c decrement; 95% confidence interval, 0.58 to 0.91; P=0.005). CONCLUSION: This prospective cohort study demonstrates that glycemic control, diabetes duration, age, and albuminuria are important risk factors for the development of DR. More aggressive retinal screening for T2DM patients diagnosed with DR should be required in order to not miss rapid progression of DR.
Albuminuria ; Cohort Studies ; Diabetes Mellitus, Type 2* ; Diabetic Retinopathy* ; Diagnosis ; Follow-Up Studies ; Hemoglobin A, Glycosylated ; Humans ; Incidence ; Korea* ; Mass Screening ; Prospective Studies ; Retinaldehyde ; Risk Factors* ; Weights and Measures