Byung Hwan Yang

Relation between plasma brain-derived neurotrophic factor and nerve growth factor in the male patients with alcohol dependence

Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are thought to be related to neuroprotection in cell culture and animal studies. Our aim was to verify the changes in human plasma BDNF and NGF concentrations induced by chronic alcohol use. Forty-one male patients with alcohol dependence were sampled the next morning of admission and compared with 41 healthy male subjects. Plasma BDNF and NGF were assayed using an enzyme-linked immunosorbent assay (ELISA). Mean plasma BDNF level was significantly higher in the patients with alcohol dependence (3502.21+/-1726.9 pg/mL) compared with the healthy subjects (861.75+/-478.9 pg/mL) (P=.000). Mean plasma NGF level was also significantly higher in patients with alcohol dependence (137.64+/-32.7 pg/mL) than in healthy subjects (112.61+/-90.2 pg/mL) (P=.012). Plasma BDNF and NGF levels showed significant negative correlation in alcohol dependence group (r=-0.388, P=.012). Increased plasma BDNF and NGF with negative correlation in alcohol-dependent patients may have some role in the regeneration of damage done by chronic alcohol use.

Genetic polymorphisms of alcohol and aldehyde dehydrogenase, dopamine and serotonin transporters in familial and non-familial alcoholism

One hundred and eleven male patients with alcohol dependence and 123 nonalcoholic healthy men were tested for the genetic polymorphisms of alcohol dehydrogenase 2 (ADH2), aldehyde dehydrogenase 2 (ALDH2), serotonin transporter (5-HTT) and dopamine transporter (DAT1). There were significant differences in genotype frequencies of ADH2 C992G and A13543G SNPs between alcoholic patients with family history of alcohol dependence (familial) and alcoholic patients without family history (non-familial). Genotype and allele frequencies of ALDH2 G1951A SNP in familial or non-familial alcoholic patients differ from normal controls. Neither 5-HTTLPR L/S nor DAT1 G2319A SNP genotypes nor alleles discriminated alcoholic patients from normal controls. These findings suggest that the genetic characteristics of alcohol metabolism in non-familial alcoholics fall between non-alcoholism and familial alcoholics.

Cardiomyopathy associated with clozapine.

Clozapine is an atypical antipsychotic agent that is more effective than the standard neuroleptics currently used for treating refractory schizophrenia. In addition, clozapine is a drug with few extrapyramidal side effects. However, clozapine is also associated with potentially serious adverse effects, such as cardiac complications as well as agranulocytosis. Clozapine-related cardiomyopathy has not been previously reported in East Asia. This report describes a 31-year-old Korean male patient with schizophrenia who developed dilated cardiomyopathy on treatment with clozapine. The removal of clozapine caused subsequent physical improvement. However, the readministration of clozapine for managing relapse of psychosis caused a recurrence of dilated cardiomyopathy in this patient. Therefore, this is the 1st report showing that the 2nd trial of clozapine caused recurrence of cardiomyopathy associated with clozapine. Thus, this report adds important support for a causal relation between clozapine and cardiac complications. In conclusion, this report attempts to raise awareness of clozapine-related cardiomyopathy.

Naltrexone influences protein kinase Cε and integrin α7 activity in SH-SY5Y neuroblastoma cells

Alcohol influences the neuroadaptation of brain cells where receptors and enzymes like protein kinase C (PKC) exist. Naltrexone acts on opioid receptors. However, other mechanisms of action remain unknown. We prepared SH-SY5Y neuroblastoma cells, and fed them with 150 mM ethanol for 72 h followed by treatment with naltrexone for 24 h. We performed microarray analysis and reverse transcriptase-polymerase chain reaction. Our results showed that PKCε increased 1.90 times and showed an overall decreasing pattern as time increased. Phosphorylated ERK also increased 2.0 times according to the change of PKCε. Integrin α7 increased 2.32 times and showed an increasing pattern as time increased. In conclusion, naltrexone influences PKCε neuronal signaling system and endothelial adhesion molecule integrin α7 in addition to the well-known opioid system.

Increased Transforming Growth Factor-beta1 in Alcohol Dependence

Ethanol and its metabolite acetaldehyde increase transforming growth factor beta1 (TGF-β1) expression in animal studies. TGF-β1 is related with the hepatic stellate cell (the key element of hepatic fibrogenesis) and the radial glia (the key element of neuronal migration). Blood samples were collected from 41 patients with alcohol dependence, TGF-β1 levels measured by ELISA were compared with 41 normal subjects. Plasma TGF-β1 levels in the patients with alcohol dependence (1,653.11±532.45 pg/mL) were significantly higher than those of healthy subjects (669.87±366.53 pg/mL) (P=0.000). Patients with or without liver pathology showed no difference in TGF-β1 (P=0.36). Increased TGF-β1 may mediate deleterious effect of alcohol such as hepatic fibrosis and suppressed neuronal developments in alcohol dependence patients.