Objectives: . Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by recurrent epistaxis, telangiectasia, and visceral arteriovenous malformations (AVMs). Activin A receptor-like type 1 (ACVRL1/ALK1) and endoglin (ENG) are the principal genes whose mutations cause HHT. No multicenter study has yet investigated correlations between genetic variations and clinical outcomes in Korean HHT patients. Methods: . Seventy-two members from 40 families suspected to have HHT based on symptoms were genetically screened for pathogenic variants of ACVRL1 and ENG. Patients with genetically diagnosed HHT were also evaluated. Results: . In the HHT genetic screening, 42 patients from 24 of the 40 families had genetic variants that met the pathogenic criteria (pathogenic very strong, pathogenic strong, pathogenic moderate, or pathogenic supporting) based on the American College of Medical Genetics and Genomics Standards and Guidelines for either ENG or ACVRL1: 26 from 12 families (50%) for ENG, and 16 from 12 families (50%) for ACVRL1. Diagnostic screening of 42 genetically positive HHT patients based on the Curaçao criteria revealed that 24 patients (57%) were classified as having definite HHT, 17 (41%) as having probable HHT, and 1 (2%) as unlikely to have HHT. Epistaxis was the most common clinical presentation (38/42, 90%), followed by visceral AVMs (24/42, 57%) and telangiectasia (21/42, 50%). Five patients (12%) did not have a family history of HHT clinical symptoms. Conclusion . Only approximately half of patients with ACVRL1 or ENG genetic variants could be clinically diagnosed as having definite HHT, suggesting that genetic screening is important to confirm the diagnosis.

Neuroinflammation is an important process underlying a wide variety of neurodegenerative diseases. Carvacrol (CAR) is a phenolic monoterpene commonly used as a food additive due to its antibacterial properties, but it has also been shown to exhibit strong antioxidative, anti-inflammatory, and neuroprotective effects. Here, we sought to investigate the effects of CAR on inflammation in the hippocampus and prefrontal cortex, as well as the molecular mechanisms underlying these effects. In our study, lipopolysaccharide was injected into the lateral ventricle of rats to induce memory impairment and neuroinflammation. Daily administration of CAR (25, 50, and 100 mg/kg) for 21 days improved recognition, discrimination, and memory impairments relative to untreated controls. CAR administration significantly attenuated expression of several inflammatory factors in the brain, including interleukin-1β, tumor necrosis factor-α, and cyclooxygenase-2. In addition, CAR significantly increased expression of brain-derived neurotrophic factor (BDNF) mRNA, and decreased expression of Toll-like receptor 4 (TLR4) mRNA. Taken together, these results show that CAR can improve memory impairment caused by neuroinflammation. This cognitive enhancement is due to the anti-inflammatory effects of CAR medicated by its regulation of BDNF and TLR4. Thus, CAR has significant potential as an inhibitor of memory degeneration in neurodegenerative diseases.
Animals ; Brain ; Brain-Derived Neurotrophic Factor ; Cyclooxygenase 2 ; Cytokines ; Discrimination (Psychology) ; Food Additives ; Hippocampus ; Inflammation ; Lateral Ventricles ; Lipopolysaccharides ; Memory ; Necrosis ; Neurodegenerative Diseases ; Neuroprotective Agents ; Phenol ; Prefrontal Cortex ; Rats ; RNA, Messenger ; Toll-Like Receptor 4

Comprehension of the medical diagnoses of doctors and treatment of diseases is important to understand the underlying principle in selecting appropriate acupoints. The pattern recognition process that pertains to symptoms and diseases and informs acupuncture treatment in a clinical setting was explored. A total of 232 clinical records were collected using a Charting Language program. The relationship between symptom information and selected acupoints was trained using an artificial neural network (ANN). A total of 11 hidden nodes with the highest average precision score were selected through a tenfold cross-validation. Our ANN model could predict the selected acupoints based on symptom and disease information with an average precision score of 0.865 (precision, 0.911; recall, 0.811). This model is a useful tool for diagnostic classification or pattern recognition and for the prediction and modeling of acupuncture treatment based on clinical data obtained in a real-world setting. The relationship between symptoms and selected acupoints could be systematically characterized through knowledge discovery processes, such as pattern identification.
Acupuncture Points ; Acupuncture Therapy ; Humans ; Neural Networks (Computer) ; Republic of Korea ; Syndrome

Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, and anxiety that may involve the release of monoamines in the fear circuit. The reported pharmacological properties of tetramethylpyrazine (TMP) include anti-cancer, anti-diabetic, anti-atherosclerotic, and neuropsychiatric activities. However, the anxiolytic-like effects of TMP and its mechanism of action in PTSD are unclear. This study measured several anxiety-related behavioral responses to examine the effects of TMP on symptoms of anxiety in rats after single prolonged stress (SPS) exposure by reversing the serotonin (5-HT) and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Rats were given TMP (10, 20, or 40 mg/kg, i.p.) for 14 days after SPS exposure. Administration of TMP significantly reduced grooming behavior, increased the time spent and number of visits to the open arm in the elevated plus maze test, and significantly increased the number of central zone crossings in the open field test. TMP administration significantly reduced the freezing response to contextual fear conditioning and significantly restored the neurochemical abnormalities and the SPS-induced decrease in 5-HT tissue levels in the prefrontal cortex and hippocampus. The increased 5-HT concentration during TMP treatment might be partially attribute to the tryptophan and 5-hydroxyindoleacetic acid mRNA level expression in the hippocampus of rats with PTSD. These findings support a role for reducing the altered serotonergic transmission in rats with PTSD. TMP simultaneously attenuated the HPA axis dysfunction. Therefore, TMP may be useful for developing an agent for treating psychiatric disorders, such those observed in patients with PTSD.
Animals ; Anxiety ; Arm ; Freezing ; Grooming ; Hippocampus ; Humans ; Models, Animal* ; Prefrontal Cortex ; Rats* ; RNA, Messenger ; Serotonin ; Stress Disorders, Post-Traumatic* ; Thymidine Monophosphate ; Tryptophan

Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, anxiety, depression, and amnesic symptoms that may involve the release of monoamines in the fear circuit. The present study measured several anxiety-related behavioral responses to examine the effects of berberine (BER) on symptoms of anxiety in rats after single prolonged stress (SPS) exposure, and to determine if BER reversed the dopamine (DA) dysfunction. Rats received BER (10, 20, or 30 mg/kg, intraperitoneally, once daily) for 14 days after SPS exposure. BER administration significantly increased the time spent in the open arms and reduced grooming behavior during the elevated plus maze test, and increased the time spent in the central zone and the number of central zone crossings in the open field test. BER restored neurochemical abnormalities and the SPS-induced decrease in DA tissue levels in the hippocampus and striatum. The increased DA concentration during BER treatment may partly be attributed to mRNA expression of tyrosine hydroxylase and the DA transporter in the hippocampus, while BER exerted no significant effects on vesicular monoamine transporter mRNA expression in the hippocampus of rats with PTSD. These results suggest that BER had anxiolytic-like effects on behavioral and biochemical measures associated with anxiety. These findings support a role for reduced anxiety altered DAergic transmission and reduced anxiety in rats with PTSD. Thus, BER may be a useful agent to treat or alleviate psychiatric disorders like those observed in patients with PTSD.
Animals ; Anxiety* ; Arm ; Berberine* ; Depression ; Dopamine* ; Grooming ; Hippocampus ; Humans ; Rats* ; RNA, Messenger ; Stress Disorders, Post-Traumatic* ; Tyrosine 3-Monooxygenase ; Vesicular Monoamine Transport Proteins

OBJECTIVESTo clarify the effects of acupuncture stimulation at Zusanli (ST 36) on the hormonal changes.

METHODSEight-week-old male C57BL/6 mice received acupuncture stimulation at acupoint ST 36 or Quchi (LI 11) once a day for 3 or 5 days in the acupuncture-stimulated groups, but not received in the normal group (n=6 in each group). On day 3 or 5, animals were given 0.1 mL of charcoal orally with a bulbed steel needle, 30 min after the last acupuncture stimulation. Ten minutes later, mice were anesthetized, and the intestinal transit and the concentrations of vasoactive intestinal peptide (VIP), motilin, ghrelin and gastrin in the serum were measured.

RESULTSCompared to no acupuncture stimulation, acupuncture stimulation at ST 36 for 5 days increased the intestinal transit and down-regulated the concentration of VIP and up-regulated the concentrations of motilin, ghrelin and gastrin (P<0.05 or 0.01), whereas acupuncture stimulation at LI 11 did not change them signifificantly (P>0.05).

CONCLUSIONAcupuncture stimulation at ST 36 for 5 days enhances the small intestinal motility and regulates the secretion of hormones related to small intestinal motility.

Acupuncture Points ; Acupuncture Therapy ; Animals ; Gastrointestinal Motility ; physiology ; Hormones ; blood ; Intestine, Small ; physiology ; Male ; Mice, Inbred C57BL

BACKGROUND/AIMS: Colonoscopic perforations have been managed with exploratory laparotomy, and have resulted in some morbidity and mortality. Recently, laparoscopic surgery is commonly performed for this purpose. The aim of this study was to compare the outcomes of several management strategies for iatrogenic colonoscopic perforations. METHODS: We retrospectively reviewed the medical records of patients who had been treated for colonoscopic perforation between January 2004 and April 2013 at CHA Bundang Medical Center in Korea. RESULTS: A total of 41 patients with colonoscopic perforation were enrolled. Twenty patients underwent conservative management with a success rate of 90%. Surgical management was performed in 23 patients including two patients who were converted to surgical management after the failure of the initial conservative management. Among 14 patients who underwent surgery at 8 hours after the perforation, there was no considerable difference in adverse outcomes between the laparotomy group and the laparoscopic surgery group. The medical costs and claim rate were 1.45 and 1.87 times greater in the exploratory laparotomy group, respectively. CONCLUSIONS: Conservative management of colonoscopic perforation could be an option for patients without overt symptoms of peritonitis or with a small defect size. If surgical management is required, laparoscopic surgery may be considered as the initial procedure even with a delayed diagnosis.
Colonoscopy ; Delayed Diagnosis ; Humans ; Korea ; Laparoscopy ; Laparotomy ; Medical Records ; Methods* ; Mortality ; Peritonitis ; Retrospective Studies

We examined whether wogonin (WO) improved hippocampal neuronal activity, behavioral alterations and cognitive impairment, in rats induced by administration of trimethyltin (TMT), an organotin compound that is neurotoxic to these animals. The ability of WO to improve cognitive efficacy in the TMT-induced neurodegenerative rats was investigated using a passive avoidance test, and the Morris water maze test, and using immunohistochemistry to detect components of the acetylcholinergic system, brain-derived neurotrophic factor (BDNF), and cAMP-response element-binding protein (CREB) expression. Rats injected with TMT showed impairments in learning and memory and daily administration of WO improved memory function, and reduced aggressive behavior. Administration of WO significantly alleviated the TMT-induced loss of cholinergic immunoreactivity and restored the hippocampal expression levels of BDNF and CREB proteins and their encoding mRNAs to normal levels. These findings suggest that WO might be useful as a new therapy for treatment of various neurodegenerative diseases.
Animals ; Brain-Derived Neurotrophic Factor ; Cholinergic Neurons ; Cognition Disorders ; Cyclic AMP Response Element-Binding Protein ; Immunohistochemistry ; Learning ; Memory ; Neurodegenerative Diseases ; Neurons* ; Rats* ; RNA, Messenger ; Water

Pro-inflammatory cytokine and brain-derived neurotrophic factor (BDNF) are modulated in post-traumatic stress disorder (PTSD). This study investigated the effects of ibuprofen (IBU) on enhanced anxiety in a rat model of PTSD induced by a single prolonged stress (SPS) procedure. The effects of IBU on inflammation and BDNF modulation in the hippocampus and the mechanisms underlying for anxiolytic action of IBU were also investigated. Male Sprague-Dawley rats were given IBU (20 or 40 mg/kg, i.p., once daily) for 14 days. Daily IBU (40 mg/kg) administration signifi cantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index in the EPM test, and increased the time spent in the center of an open fi eld after SPS. IBU administration signifi cantly decreased the expression of pro-inflammatory mediators, such as tumor necrosis factor-α, interleukin-1β, and BDNF, in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. These fi ndings suggest that IBU exerts a therapeutic effect on PTSD that might be at least partially mediated by alleviation of anxiety symptoms due to its anti-inflammatory activity and BDNF expression in the rat brain.
Animals ; Anxiety ; Arm ; Brain ; Brain-Derived Neurotrophic Factor ; Hippocampus ; Humans ; Ibuprofen* ; Immunohistochemistry ; Inflammation ; Male ; Models, Animal* ; Necrosis ; Rats* ; Rats, Sprague-Dawley ; Stress Disorders, Post-Traumatic*

beta-asarone (BAS) is an active component of Acori graminei rhizoma, a traditional medicine used clinically in treating dementia and chronic stress in Korea. However, the cognitive effects of BAS and its mechanism of action have remained elusive. The purpose of this study was to examine whether BAS improved spatial cognitive impairment induced in rats following chronic corticosterone (CORT) administration. CORT administration (40 mg/kg, i.p., 21 days) resulted in cognitive impairment in the avoidance conditioning test (AAT) and the Morris water maze (MWM) test that was reversed by BAS (200 mg/kg, i.p). Additionally, as assessed by immunohistochemistry and RT-PCR analysis, the administration of BAS significantly alleviated memory-associated decreases in the expression levels of brain-derived neurotrophic factor (BDNF) and cAMP-response element-binding protein (CREB) proteins and mRNAs in the hippocampus. Also, BAS administration significantly restored the expression of Bax and Bcl-2 mRNAs in the hippocampus. Thus, BAS may be an effective therapeutic for learning and memory disturbances, and its neuroprotective effect was mediated, in part, by normalizing the CORT response, resulting in regulation of BDNF and CREB functions and anti-apoptosis in rats.
Animals ; Apoptosis* ; Brain-Derived Neurotrophic Factor ; Corticosterone* ; Dementia ; Hippocampus* ; Immunohistochemistry ; Korea ; Learning ; Medicine, Traditional ; Memory ; Memory, Short-Term* ; Neuroprotective Agents ; Rats* ; RNA, Messenger ; Water