Korean red ginseng excitation of paraventricular nucleus neurons via non-N-methyl-D-aspartate glutamate receptor activation in mice

It has been reported that Korean red ginseng (KRG), a valuable and important traditional medicine, has varied effects on the central nervous system, suggesting its activities are complicated. The paraventricular nucleus (PVN) neurons of the hypothalamus has a critical role in stress responses and hormone secretions. Although the action mechanisms of KRG on various cells and systems have been reported, the direct membrane effects of KRG on PVN neurons have not been fully described. In this study, the direct membrane effects of KRG on PVN neuronal activity were investigated by using a perforated patch-clamp in ICR mice. In gramicidin perforated patch-clamp mode, KRG extract (KRGE) induced repeatable depolarization followed by hyperpolarization of PVN neurons. The KRGE-induced responses were concentration-dependent and persisted in the presence of tetrodotoxin, a voltage sensitive Na+ channel blocker. The KRGE-induced responses were suppressed by 6-cyano-7-nitroquinoxaline-2,3-dione (10 µM), a non-N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, but not by picrotoxin, a type A gamma-aminobutyric acid receptor antagonist. The results indicate that KRG activates non-NMDA glutamate receptors of PVN neurons in mice, suggesting that KRG may be a candidate for use in regulation of stress responses by controlling autonomic nervous system and hormone secretion.

Developmental changes in GABAA tonic inhibition are compromised by multiple mechanisms in preadolescent dentate gyrus granule cells

The sustained tonic currents (I(tonic)) generated by γ-aminobutyric acid A receptors (GABA(A)Rs) are implicated in diverse age-dependent brain functions. While various mechanisms regulating I(tonic) in the hippocampus are known, their combined role in I(tonic) regulation is not well understood in different age groups. In this study, we demonstrated that a developmental increase in GABA transporter (GAT) expression, combined with gradual decrease in GABA(A)R α₅ subunit, resulted in various I(tonic) in the dentate gyrus granule cells (DGGCs) of preadolescent rats. Both GAT-1 and GAT-3 expression gradually increased at infantile (P₆₋₈ and P₁₃₋₁₅) and juvenile (P₂₀₋₂₂ and P₂₇₋₂₉) stages, with stabilization observed thereafter in adolescents (P₃₄₋₃₆) and young adults (P₄₁₋₄₃). I(tonic) facilitation of a selective GAT-1 blocker (NO-711) was significantly less at P₆₋₈ than after P₁₃₋₁₅. The facilitation of I(tonic) by SNAP-5114, a GAT-3 inhibitor, was negligible in the absence of exogenous GABA at all tested ages. In contrast, I(tonic) in the presence of a nonselective GAT blocker (nipecotic acid, NPA) gradually decreased with age during the preadolescent period, which was mimicked by I(tonic) changes in the presence of exogenous GABA. I(tonic) sensitivity to L-655,708, a GABA(A)R α₅ subunit inverse agonist, gradually decreased during the preadolescent period in the presence of NPA or exogenous GABA. Finally, Western blot analysis showed that the expression of the GABA(A)R α₅ subunit in the dentate gyrus gradually decreased with age. Collectively, our results suggested that the I(tonic) regulation of altered GATs is under the final tune of GABA(A)R α₅ subunit activation in DGGCs at different ages.

Facilitation of AMPA receptor-mediated steady-state current by extrasynaptic NMDA receptors in supraoptic magnocellular neurosecretory cells

In addition to classical synaptic transmission, information is transmitted between cells via the activation of extrasynaptic receptors that generate persistent tonic current in the brain. While growing evidence supports the presence of tonic NMDA current (INMDA) generated by extrasynaptic NMDA receptors (eNMDARs), the functional significance of tonic I(NMDA) in various brain regions remains poorly understood. Here, we demonstrate that activation of eNMDARs that generate I(NMDA) facilitates the α-amino-3-hydroxy-5-methylisoxazole-4-proprionate receptor (AMPAR)-mediated steady-state current in supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs). In low-Mg2+ artificial cerebrospinal fluid (aCSF), glutamate induced an inward shift in I(holding) (I(GLU)) at a holding potential (V(holding)) of -70 mV which was partly blocked by an AMPAR antagonist, NBQX. NBQX-sensitive I(GLU) was observed even in normal aCSF at V(holding) of -40 mV or -20 mV. I(GLU) was completely abolished by pretreatment with an NMDAR blocker, AP5, under all tested conditions. AMPA induced a reproducible inward shift in I(holding) (I(AMPA)) in SON MNCs. Pretreatment with AP5 attenuated I(AMPA) amplitudes to ~60% of the control levels in low-Mg2+ aCSF, but not in normal aCSF at V(holding) of -70 mV. I(AMPA) attenuation by AP5 was also prominent in normal aCSF at depolarized holding potentials. Memantine, an eNMDAR blocker, mimicked the AP5-induced I(AMPA) attenuation in SON MNCs. Finally, chronic dehydration did not affect I(AMPA) attenuation by AP5 in the neurons. These results suggest that tonic I(NMDA), mediated by eNMDAR, facilitates AMPAR function, changing the postsynaptic response to its agonists in normal and osmotically challenged SON MNCs.

The Link between Health-related Physical Fitness Level and Cardiovascular Disease-related Risk Factors / 한국직업건강간호학회지

PURPOSE: The purpose of this study was to identify the link between health-related physical fitness level and cardiovascular disease-related risk factors in adult male workers. METHODS: We tested cardiovascular disease- related risk factors (waist circumference, SBP, DPB, fasting glucose, TC, HDL-C, TG, LDL-C) and health-related physical fitness (VO2max, grip, Sit-up, Flexibility, Body fat) and divided health-related physical fitness level of the subjects into 3 groups - A (very good, n=56), B (good, n=59), and C (below-average, n=57) according to the criterion of the Health and Fitness counseling guidelines of KOSHA. The statistical techniques such as standard deviation, one-way ANOVA and multiple regression (p<.05) were used. RESULTS: There were significant differences between group C and group B & A (p<.001) in waist circumference, DBP, Fasting glucose, HDL-C, TG, LDL-C. In TC/HDL-C, TG/HDL-C, LDL-C/HDL-C, Group C was higher than group B and A. CONCLUSION: On the basis of these results, we identified that improvement of health-related physical fitness level positively effects on the decrease of cardiovascular disease-related risk factors.

SM709, Ingredient of Antimelanogenic Bamboo Extract, Blocks Endothelin-1-induced Ca2+i Increase in Human Melanocytes

Endothelins secreted from keratinocytes are intrinsic mitogens and melanogens of human melanocytes in UVB-induced hyperpigmentation. To elucidate the cellular mechanism of antimelanogenic activity of bamboo extract, the effects of three ingredients of bamboo extract on endothelin 1 (ET-1) -induced Ca2+ mobilization were investigated in cultured human melanocytes. ET-1 receptors in human melanocytes were characterized by using specific antagonist, and ET-1 was found to increase intracellular Ca2+ concentration ([Ca2+]i) by activating ET-B receptor. SM709 (1, 2-O-diferulyl-glycerol), an ingredient of bamboo extract, inhibited ET-1-induced [Ca2+]i increase in a concentration- and time-dependent manner, although another ingredients SM707 and SM708 had no effect on ET-1-induced [Ca2+]i increase in human melanocytes. SM709 (100 microM), however, did not affect [Ca2+]i increase induced by thapsigargin and caffeine, suggesting that SM709 has no effect on the Ca2+ store in melanocytes. Furthermore, SM709 did not affect [Ca2+]i increase induced by LPA or ATP, known as G protein-mediated PLC activators like ET-1. Taken together, it is suggested that SM709 antagonizes ET-1-induced transmembrane signaling through ET-B receptor, which maybe a possible underlying mechanism of antimelanogenic activity of bamboo extract in human melanocytes.

The Clinical study of Lung Cancer in Patients Younger than 40 Years of Age / 결핵

BACKGROUND: Bronchogenic carcinoma is generally considered as a disease that predominantly affects middle-aged and elderly men. A small percentage of patients with lung cancer are diagnosed in the third or fourth decade of life or earlier. The current study was performed to review the clinical characteristics of bronchogenic carcinoma in patients younger than 40 years of age at Chungnam National University Hospital. METHOD: To determine the clinicopathologic characteristics including survival rates of lung cancer patients younger than 40 years of age and to compare them with those of patients older than 40 years of age at diagnosis, data of 905 patients diagnosed as lung cancer from January 1990 to March 1997 were analyzed. RESULT: Twenty-three of 805 patients(2.5%) belonged to the young age group (less than 40 years). Male to female ratios of young age group and control group were 2.8 : 1 and 5.3 : 1, respectively. The mean duration of symptoms from onset to the definite diagnosis was 3.2 months in the young age group. The most common initial symptoms in the young age group were cough(52.2%) and dyspnea(43.5%). Adenocarcinoma(43.5%) was more frequent in the young age group than in the control group(20.1%). Stage III and IV(70%) tumors were more frequent in the young age group than in the control group(52.3%). Distant metastasis rae of the young age group(56.6%) was higher than that of the control group(22.3%). CONCLUSION: The predominance of adenocarcinoma, the lower male-female ratio, and the high incidence of advanced stage tumor at diagnosis are the characteristics of lung cancer in patients younger than 40 years of age.

Clinical effects of neoafjuvant chemotherapy in stage IIIA non-small cell lung cancer / 대한내과학회지

BACKGROUND: Surgical therapy remains the only curative treatment of localized non-small cell lung cancer(NSCLC). But the efficacy of surgery for patients with NSCLC is limited, although recent studies suggest that neoadjuvant chemotherapy may improve survival. Many studies also demonstrated benefit for neoadjuvant therapy. However very few studies about neoadjuvant chemotherapy were reported in Korea. We conducted this study to examine the possible benefit of neoadjuvant chemotherapy in patients with operable stage IIIA NSCLC. METHODS: Twenty seven patients(25 men and 2 women) with clinical stage IIIA NSCLC were analyzed. The patients received 2 to 4 courses of cisplatin based chemotherapy and followed by surgery. To compare the resection rate and survival, 12 patients(10 men, 2 women) with clinical stage IIIA and initially treated operation were also anayzed. RESULTS: The radiologically assessed response rate to the neoadjuvant therapy was 59.3%. Twelve seven patients underwent gross tumor resection with 24(88.9%) having complete resection and 21(77.8%) having postaperative stage I ar II. Pathologically defined response in nodal staging was more higher(85.2%). There was no difference of relapse free interval in recurred patients between two groups. But in patients treated with neoadjuvant therapy, distant recurrence is less higher than local recurrence. The median period of survival was 42 months in the patients treated with neoadjuvant therapy, and 27 months in the patients initially treated with surgery(p=0.287). CONCLUSION: The neoadjuvant chemotherapy improves local tumor control and lowers the distant recurrence. There was a possible trend improving median survival. So neoadjuvant chemotherapy might be considered as a standard therapy in stage IIIA NSCLC.

The Clinical significance of STAT-PAT-PAK ULTRA FAST(R) and ICT Tuberculosis for Serologic Diagnosis of Tuberculosis / 결핵

BACKGROUND: In recent years, tuberculosis has re-emerged as a major health problem in both industrialized and developing countries. Recent advances in identifying and purifying antigens secreted in active tuberculosis infection have lead to the development of serological assays based on a number of immunodominant antigens. To date, the most sensitive and specific of these antigens has been the 38-kDa antigen. METHOD: Two rapid membrane-based serologic assays using antigen(38-kDa) from mycobacterium tuberculosis for the diagnosis of tuberculosis were evaluated in 22 patients with smear-positive pulmonary tuberculosis, 14 patients with inactive pulmonary tuberculosis, and 9 patients with non-tuberculous lung disease. RESULT: The evaluation of validity(sensitivity, specificity, positive predictive value, negative predictive value, false positivity and false negativity) of STAT-PAK ULTRA FAST(R) were 77.3%, 28.6%, 63.0%, 44.4%, 71.4%, and 22.7% for differential diagnosis of active pulmonary tuberculosis and inactive pulmonary tuberculosis, respectively. The evaluation of validity of STAT-PAK ULTRA FAST(R) were 77.3%, 33.3%, 73.9%, 37.5%, 66.7%, and 22.7% for differential diagnosis of active pulmonary tuberculosis and non-tuberculosis. The evaluation of validity of ICT Tuberculosis were 54.5%, 57%, 66.7%, 44.4%, 42.9%, and 45.5% for differential diagnosis of active pulmonary tuberculosis and inactive pulmonary tuberculosis. The evaluation of validity of ICT Tuberculosis were 54.5%, 100%, 100%, 47.4%, 0%, and 45.4% for differential diagnosis of active pulmonary tuberculosis and non-tuberculosis. CONCLUSION: We concluded no effectiveness of STAT-PAK ULTRA FAST(R) and ICT tuberculosis on serologic diagnosis of pulmonary tuberculosis. In the future, further large-scale study should be needed for serologic diagnosis of pulmonary tuberculosis.

Immunohistochemical Detection of p53, erbB-2 and CEA Oncoprotein in Lung Cancer Clinical Correlations / 결핵

BACKGROUND: The prognosis of patients with lung cancer is still poor. Lung cancer exhibits a variable clinical outcome, even in those patients with same stage Numerous reports suggest that oncogene expression night play a role in explaining the variability of response and survival But many of these reports are still under debete. So we studied the clinical relevance of oncogene expression in Korean lung cancer patients. lmmunohistochemistry of p53, erbB-2, CEA expression was performed. METHOD: From March, 1992 until March, 1997, 120 patients with lung cancer were reviewed. p53, erbB-2, and CEA expression were detected on paraffin-embedded tumor blocks with the use of monoclonal antibodies. The survival arid response has correlated with the expressibility of p53, erbE-2, arid CEA oncoprotein. RESULTS: Overall, the expression rates of p53 erbB-2, and CEA were 33.7%, 59.3%, and 32.6% respectively. Expression rates were not con-elated to cell type or stage. Compared with response to chemotherapy, no correlation was found. The expression of p53, erbB-2, or CEA was not correlated with 2-year survival. With simultaneous applications of p53. erbB-2, and CEA, patients with 2 or more expressions also did not show poor response to chemotherapy. CONCLUISON: We conclude the p53, erbB-2, and CEA expression are clinically less useful in predicting response to chemotherapy or survival.