Transient receptor potential vanilloid subtype 1 (TRPV1) on astrocytes prevents ongoing degeneration of nigrostriatal dopamine (DA) neurons in MPP⁺-lesioned rats via ciliary neurotrophic factor (CNTF). The present study determined whether such a beneficial effect of astrocytic TRPV1 could be achieved after completion of injury of DA neurons, rather than ongoing injury, which seems more relevant to therapeutics. To test this, the MPP⁺-lesioned rat model utilized here exhibited approximately 70~80% degeneration of nigrostriatal DA neurons that was completed at 2 weeks post medial forebrain bundle injection of MPP⁺. TRPV1 agonist, capsaicin (CAP), was intraperitoneally administered. CNTF receptor alpha neutralizing antibody (CNTFRαNAb) was nigral injected to evaluate the role of CNTF endogenously produced by astrocyte through TRPV1 activation on DA neurons. Delayed treatment of CAP produced a significant reduction in amphetamine-induced rotational asymmetry. Accompanying this behavioral recovery, CAP treatment increased CNTF levels and tyrosine hydroxylase (TH) activity in the substantia nigra pars compacta (SNpc), and levels of DA and its metabolites in the striatum compared to controls. Interestingly, behavioral recovery and increases in biochemical indices were not reflected in trophic changes of the DA system. Instead, behavioral recovery was temporal and dependent on the continuous presence of CAP treatment. The results suggest that delayed treatment of CAP increases nigral TH enzyme activity and striatal levels of DA and its metabolites by CNTF endogenously derived from CAP-activated astrocytes through TRPV1, leading to functional recovery. Consequently, these findings may be useful in the treatment of DA imbalances associated with Parkinson's disease.
Animals ; Antibodies, Neutralizing ; Astrocytes ; Capsaicin ; Ciliary Neurotrophic Factor ; Dopamine ; Dopaminergic Neurons ; Medial Forebrain Bundle ; Models, Animal ; Neurons ; Parkinson Disease ; Pars Compacta ; Rats ; Receptor, Ciliary Neurotrophic Factor ; Tyrosine 3-Monooxygenase

BACKGROUND/AIMS: Carnitine and vitamin complex (Godex(R)) is widely used in patients with chronic liver disease who show elevated liver enzyme in South Korea. The purpose of this study is to identify the efficacy and safety of carnitine from entecavir combination therapy in Alanine aminotransferase (ALT) elevated Chronic Hepatitis B (CHB) patients. METHODS: 130 treatment-naive patients with CHB were enrolled from 13 sites. The patients were randomly selected to the entecavir and the complex of entecavir and carnitine. The primary endpoint of the study is ALT normalization level after 12 months. RESULTS: Among the 130 patients, 119 patients completed the study treatment. The ALT normalization at 3 months was 58.9% for the monotherapy and 95.2% for the combination therapy (P<0.0001). ALT normalization rate at 12 months was 85.7% for the monotherapy and 100% for the combination group (P=0.0019). The rate of less than HBV DNA 300 copies/mL at 12 months was not statistically significant (P=0.5318) 75.9% for the monotherapy, 70.7% for the combination and it was. Quantification of HBsAg level was not different from the monotherapy to combination at 12 months. Changes of ELISPOT value to evaluate the INF-gamma secretion by HBsAg showed the increasing trend of combination therapy compare to mono-treatment. CONCLUSIONS: ALT normalization rate was higher in carnitine complex combination group than entecavir group in CHB. Combination group was faster than entecavir mono-treatment group on ALT normalization rate. HBV DNA normalization rate and the serum HBV-DNA level were not changed by carnitine complex treatment.
Adult ; Alanine Transaminase/blood ; Antiviral Agents/*therapeutic use ; Carnitine/*therapeutic use ; DNA, Viral/analysis ; Drug Therapy, Combination ; Enzyme-Linked Immunospot Assay ; Female ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B Surface Antigens/blood ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/*drug therapy ; Humans ; Interferon-gamma/metabolism ; Male ; Middle Aged ; Mitochondria/physiology ; Treatment Outcome ; Vitamin B Complex/*therapeutic use

BACKGROUND/AIMS: The incidence of Hepatitis B has significantly declined since the introduction of an HBV vaccination program. The aim of this study was to investigate recent clinical features of acute viral hepatitis B (AVH-B) in Korea. METHODS: A total of 2241 patients with acute viral hepatitis were enrolled and their data were collected from nine medical-centers between January 2006 and December 2009. RESULTS: One hundred nineteen (5.3%) of the 2241 were diagnosed as AVH-B. Among 78 patients with AVH-B whose data were analyzed, 50 were male, and the mean age was 38.6 years. In an initial test, mean AST, ALT and total-bilirubin levels were 1296.2 IU/L, 2109.6 IU/L and 9.3 mg/dl, respectively. Positivity frequencies for HBeAg and anti-HBe were 55.1% and 67.9%, respectively, and the mean HBV DNA level was 5.2 log10 copies/ml. The mean length of hospitalization was 11.6 days. During follow-up, AST, ALT and total bilirubin levels were normalized or near-normalized in all patients without serious complications. Sixty-three of 66 (95.4%) patients showed HBsAg loss and 37 (56.1%) patients showed HBsAg seroconversion. Only 3 patients (4.5%) showed persistent hepatitis B viremia. There was no case of death or liver transplantation. Nine patients (11.3%) had received anti-viral agents and their clinical outcomes were not significantly different from those of patients treated without antiviral agents. CONCLUSIONS: The prevalence of AVH-B among acute hepatitis patients is relatively low in Korea. AVH-B infection can be cured without complications in almost all patients, regardless of antiviral treatment.
Acute Disease ; Adult ; Alanine Transaminase/blood ; Antiviral Agents/therapeutic use ; Aspartate Aminotransferases/blood ; Bilirubin/blood ; DNA, Viral/analysis ; Female ; Hepatitis B/*diagnosis/drug therapy/epidemiology ; Hepatitis B Antibodies/blood ; Hepatitis B e Antigens/blood/immunology ; Humans ; Male ; Middle Aged ; Retrospective Studies

Duodenal varix is a rare cause of hemorrhage in patients with portal hypertension, however their rupture is serious and often life threatening. Treatments for duodenal variceal bleeding include endoscopic procedures, surgery, or interventional radiologic procedures. We report a case of duodenal varices rupture in a 45-year-old man with alcoholic liver cirrhosis who presented with melena and dizziness. Emergent upper endoscopy revealed large nodular varices with a ruptured erosion on the top in the distal second portion of duodenum. Two consecutive injections with 1.0 mL of n-butyl-2-cyanoacrylate (Histoacryl; Braun-Melsungen, Germany) mixed with 1.0 mL of lipiodol (Laboratoire-Guerbet, France) were performed intravariceally and achieved successful hemostasis. This suggests that endoscopic injection sclerotherapy with histoacryl may be an effective therapeutic option for the control of ruptured duodenal variceal bleeding.
Duodenal Diseases/etiology/*therapy ; Duodenoscopy ; Duodenum/*blood supply ; Enbucrilate/*analogs & derivatives/chemistry/therapeutic use ; Gastrointestinal Hemorrhage/etiology/*therapy ; Humans ; Liver Cirrhosis, Alcoholic/complications ; Male ; Middle Aged ; Rupture ; Sclerosing Solutions/*therapeutic use ; *Sclerotherapy ; Tissue Adhesives/therapeutic use ; Tomography, X-Ray Computed ; Varicose Veins/complications/*therapy

BACKGROUND/AIMS: Recently, the incidence of acute hepatitis A has increased nationwide and is related to the low rate of IgG anti-HAV. This study compared the prevalence of IgG anti-HAV in two university hospitals located in a large city and in a small city including a rural region according to age, gender, and the year of diagnosis. METHODS: IgG anti-HAV was measured in a total of 4299 patients, who visited Seoul or Guri Hanyang University Hospital between January 2002 and December 2006. RESULTS: The positive rates of the antibody in Seoul and Guri hospitals were 52.7% vs 57.1% in under the age of 1, 40.7% vs 42.2% in age of 1 to 4, 31.8% vs 30.3% in age of 5 to 9, 24.8% vs 27.1% in age of 10 to 14, 11.6% vs 18.2% in age of 15 to 19, 23.0% vs 20.3% in age of 20 to 24, 40.5% vs 42.9% in age of 25 to 29, 67.5% vs 75.0% in age of 30 to 34, 86.5% vs 88.1% in age of 35 to 39, 95.3% vs 93.6% in age of 40 to 44, 97.0% vs 98.7% in age of 45 to 49, and 98.5% vs 98.6% in patients who were more than 50, respectively. The positive rates of the antibody were not significantly different between two sites according to each age group and gender. CONCLUSIONS: The results confirmed the low rates of IgG anti-HAV, particularly in the ages of 10-24 that match the age group of recently increased incidence of acute hepatitis A nationwide. Therefore, measurement of the antibody and vaccination should be considered in this age group.
Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Hepatitis A/*epidemiology ; Hepatitis A Antibodies/*blood ; Hepatitis A Virus, Human/immunology ; Hospitals ; Humans ; Immunoglobulin G/*blood ; Infant ; Korea/epidemiology ; Male ; Middle Aged ; Rural Population ; Seroepidemiologic Studies ; Urban Population

The combination therapy with pegylated interferon alpha and ribavirin has increasingly prescribed for chronic hepatitis C. Although many side effects of interferon such as flu-like symptoms, gastrointestinal and neuropsychiatric symptoms are well known, only several cases of interferon-induced pulmonary toxicity have been reported. Interferon-induced pulmonary toxicity usually develops from 2 weeks to 12 weeks after treatment for HCV infection. Diagnosis is commonly based on clinical findings such as a dry cough, dyspnea, hypoxemia, and a restrictive pattern in pulmonary function testing, bilateral diffuse parenchymal infiltrations, histopathological findings of interstitial pneumonitis, and exclusion of any other causative agents. Prompt withdrawal of the drug is the cornerstone of treatment. We report a case of PEG-IFN alpha-2a induced pulmonary toxicity in a 50-year-old male patient with hepatitis C. To our knowledge, this is the first case of pegylated interferon alpha-2a induced pulmonary toxicity in Korea.
Antiviral Agents/administration & dosage/*adverse effects/therapeutic use ; Hepatitis C, Chronic/*drug therapy ; Humans ; Interferon Alfa-2a/administration & dosage/*adverse effects/therapeutic use ; Lung Diseases/*chemically induced/diagnosis/pathology ; Male ; Middle Aged ; Polyethylene Glycols/administration & dosage/*adverse effects/therapeutic use ; Ribavirin/administration & dosage/therapeutic use ; Treatment Outcome

BACKGROUND/AIMS: The aim of this study was to identify non-endoscopic predictors for the presence of large esophageal varices in Korean patients with liver cirrhosis. METHODS: Among 736 patients with liver cirrhosis newly diagnosed between the year 2001 and 2005, 245 patients (171 men and 74 women, mean age of 51.9 years) fulfilled the inclusion criteria and underwent EGD as screening tests for esophageal varices. Fifteen variables were analysed to identify the presence of large esophageal varices. RESULTS: Esophageal varices were noted in 186 patients (75.9%) and large varices in 55 patients (22.4%), while 59 patients (24.1%) had no varices at the time of initial diagnosis of cirrhosis. The causes of liver cirrhosis were viral hepatitis (41.2%), chronic alcoholism (42.4%), viral hepatitis/alcoholism (9.8%), and others (6.6%). Fifty-one percent, 35.1% and 13.9% of the patients belonged to Child-Pugh class A, B, and C, respectively. Variables associated with the presence of large esophageal varices on univariate analysis were the presence of ascites, splenomegaly (long-axis > or =12 cm by ultrasound measure), alcoholism, Child-Pugh class, platelet count, prothrombin time, and albumin. On multivariate analysis, alcohol, splenomegaly, and ascites were significantly associated with the presence of large esophageal varices. If the patients have two of them, sensitivity and negative predictive value were 80% and 91.7%, respectively. Patients without all three factors had no large esophageal varices. CONCLUSIONS: These results suggest that patients who have at least two among ascites, splenomegaly, and alcoholism would have an increased risk of having large esophageal varices.
Adult ; Aged ; Ascites/diagnosis ; Esophageal and Gastric Varices/diagnosis/epidemiology/*etiology ; Female ; Humans ; Liver Cirrhosis/*complications/epidemiology ; Liver Cirrhosis, Alcoholic/*complications/epidemiology ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Predictive Value of Tests ; Prevalence ; ROC Curve ; Risk Factors ; Sensitivity and Specificity ; Severity of Illness Index ; Splenomegaly/complications

No abstract available.
Bone Regeneration* ; Humans*

OBJECTIVE: The association of neurotrophic factors with the etiology of schizophrenia has been widely studied. Among them, glial cell line-derived neurotrophic factor (GDNF) is known to promote the survival and differentiation of dopaminergic neurons. Considering dopamine hypothesis and neurodevelopmental theory, GDNF gene may be related with schizophrenia. In this study, we tried to clarify the association between schizophrenia and GDNF gene polymorphism. METHODS: Genotype and allele frequencies in the promoter and intron regions of GDNF gene were studied by using restriction fragment length polymorphism to compare 180 Korean schizophrenics with 105 Korean controls. RESULTS: We found significant differences between the schizophrenics and the controls in genotype and allele frequencies of BsaI polymorphism in the promoter region of GDNF gene (x2=18.208, df=2, p=0.0001/x2=11.264, df=1, p=0.0008). But no significant differences were found in intron region (p=0.06, p=0.984). CONCLUSION: These results suggest that polymorphism of GDNF gene might be related to the pathogenesis of schizophrenia.
Dopamine ; Dopaminergic Neurons ; Gene Frequency ; Genotype ; Glial Cell Line-Derived Neurotrophic Factor* ; Introns ; Nerve Growth Factors ; Polymorphism, Restriction Fragment Length ; Promoter Regions, Genetic ; Schizophrenia