This study was designed to examine the effects of two antidepressant drugs on the expression of c-fos mRNA in cultured embryonic rat hippocampal neurons. The drugs used were imipramine and amitriptyline. On the fourth day of culture, hippocampal neurons were treated with variable concentrations of each drug. Competitive RT-PCR(Reverse Transcriptase-PCR) analysis was used to quantify the c-fos mRNA expression induced by each drug. Experimental results showed that acute and direct treatment with imipramine and amitriptyline with relatively low concentrations(imipramine < or =10micrometer, amitriptyline < or =10micrometer) had no inductive effect on the expression of c-fos mRNA in the rat hippocampal neurons. However, after treatment with relatively high concentrations(imipramine > or =100micrometer, amitriptyline > or =100micrometer) c-fos mRNA was not detected. These findings suggest the followings. Firstly, the action mechanisms of these drugs on the hippocampal neurons might not be mediated by c-fos but by other immediate-early genes(IEGs). Secondly, their actions may be mediated indirectly via other areas of the brain. Thirdly, the expression of c-fos might be inhibited by high concentrations of these drugs, or the high concentrations could induce cell death. Finally, though cell death remains to be confirmed, the inhibition of c-fos induction or cell death could play a role in the cognitive impairments known to be adverse effects of some antidepressants. This study is believed to be a first step toward understanding the mechanisms of learning and memory. Further studies are needed to investigate the expression of various IEGs and changes in the hippocampal neurons of rat resulting from chronic treatment with antidepressant drugs.
Amitriptyline ; Animals ; Antidepressive Agents* ; Brain ; Cell Death ; Imipramine ; Learning ; Memory ; Neurons* ; Rats* ; RNA, Messenger*

OBJECTIVE: To investigate the incidence of non-responder to hormone replacement therapy (HRT) and to evaluate the bone response to HRT according to basal bone mineral density(BMD) in postmenopausal women. METHODS: A total of 211 postmenopausal women received either continuous combined estrogen-progestogen replacement (n=112) or estrogen replacement (n=99) for 1 years. BMD at the lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry (DEXA) before and 1 year after HRT. RESULTS: The incidence of non-responder (women with > 3% bone loss per year) to HRT was 9.2% in the lumbar spine, and 23.8% in femoral neck. Estrogen replacement group had a higher incidence of non-responder than combined replacement group. Non-responder group had a higher basal BMD at the lumbar spine than responder group, and showed bone loss rate of 7.6% per year. After 1 year of HRT, postmenopausal women with osteoporosis showed a higher rate of increase in BMD at the lumbar sine and femoral neck than women with normal BMD or osteopenia. CONCLUSION: The non-responders to HRT have a higher basal lumbar BMD, compared with responders. The higher basal BMD at the lumbar spine is, the less bone conservation effect of HRT is.
Absorptiometry, Photon ; Bone Density* ; Bone Diseases, Metabolic ; Estrogen Replacement Therapy ; Female ; Femur Neck ; Hormone Replacement Therapy* ; Humans ; Incidence ; Osteoporosis ; Spine

Single unit responses of the ventral posterior medial (VPM) thalamic neurons to stimulation were monitored in anesthetized rats during activation of contralateral primary somatosensory (SI) cortex by GABA antagonist. The temporal changes of afferent sensory transmission were quantitatively analyzed by poststimulus time histogram (PSTH). Mainly, afferent sensory transmission to VPM thalamus was facilitated (15 neurons of total 23) by GABA antagonist (bicuculline) applied to contralateral cortex, while 7 neurons were suppressed. However, when ipsilateral cortex was inactivated by GABA agonist, musimol, there was significant suppression of afferent sensory transmission of VPM thalamus. This suppressed responsiveness by ipsilateral musimol was not affected by bicuculline applied to contralateral cortex. These results suggest that afferent transmission to VPM thalamus may be subjected to the interhemispheric modulation via ipsilateral cortex during inactivation of GABAergic neurons in contralateral SI cortex.
Animals ; Bicuculline ; GABA Agonists ; GABA Antagonists ; GABAergic Neurons ; gamma-Aminobutyric Acid ; Neurons ; Rats ; Somatosensory Cortex* ; Thalamus*

Pulse-induced permeabilization of cellular membranes, generally referred to as electroporation (EP), has been used for years as a tool to increase macromolecule uptake in tissues, including nucleic acids, for gene therapeutic applications, and this technique has been shown to result in improved immunogenicity. In this study, we assessed the utility of EP as a tool to improve the efficacy of HB-110, a novel therapeutic DNA vaccine against chronic hepatitis B, now in phase 1 of clinical study in South Korea. The potency of HB-110 in mice was shown to be improved by EP. The rapid onset of antigen expression and higher magnitude of humoral and cellular responses in electric pulse-treated mice revealed that EP may enable a substantial reduction in the dosage of DNA vaccine required to elicit a response similar in magnitude to that achievable via conventional administration. This study also showed that EP-based vaccination at 4-week-intervals elicited a cellular immune response which was about two-fold higher than the response elicited by conventional vaccination at 2-week intervals. These results may provide a rationale to reduce the clinical dose and increase the interval between the doses in the multidose vaccination schedule. Electric pulsing also elicited a more balanced immune response against four antigens expressed by HB-110: S, preS, Core, and Pol.
Animals ; Electroporation ; Hepatitis B Antigens/biosynthesis ; Hepatitis B Vaccines/administration & dosage/*immunology ; Hepatitis B, Chronic/*immunology/prevention & control ; Immunity, Cellular ; Male ; Mice ; Mice, Inbred BALB C ; Vaccines, DNA/administration & dosage/*immunology

BACKGROUND: From Sept. 1985 to Sept. 1997, 2,000 cases of open heart surgery (OHS) were performed in the Department of Thoracic & Cardiovascular Surgery, Pusan Paik Hospital, College of Medicine, Inje University. MATERIAL AND METHOD: Among the total of 2,000 cases of OHS, 1532 cases were congenital heart disease (CHD) and 468 cases were acquired heart disease (AHD). The age distribution was 9 days (4.0kg) to 68 years in CHD and 11 to 66 years in AHD. In 1532 cases of CHD, there were 1403 acyanotic cases and 129 cyanotic cases. RESULT: The CHD cases consisted of 940 ventricular septal defects (61.4%), 324 atrial septal defects (21.1%), 112 tetralogy of Fallot (7.3%), 46 pulmonary stenosis (3%), 38 endocardial cushion defects (2.5%), 15 valsalva sinus ruptures (1%), 4 transposition of great arteries (0.3%), 4 double outlet right ventricles (0.3%), and etc. Corrective operations were applied for congenital heart disease with a result of 3.1% hospital mortality. Of 468 AHD, 381 cases were valvular heart diseases, 48 ischemic heart diseases, 12 cardiac tumors, 8 annuloaortic ectasias, 16 dissecting aortic aneurysms and etc. In the 381 valvular heart diseases, there were 226 single valve replacements (36 aortic valve replacements (AVR), 188 mitral valve replacements (MVR), and 2 tricuspid valve replacements (TVR), among these were 71 cases of double valve replacements (AVR & MVR), 54 cases of MVR with tricuspid valve annuloplasty (TVA), and 18 cases of AVR, MVR with TVA. The total implanted prosthetic valves were 466. In MVR, 123 St. Jude Medical valves, 90 Carpentier-Edwards valves, 65 CarboMedics valves, 42 Sorin valves and 16 other valves were used. In AVR, 68 St. Jude Medical valves, 36 CarboMedics valves, 14 Carpentier-Edwards valves and 9 other valves were used. Coronary Artery Bypass Surgery (CABG) were performed in 48 cases. The patterns of bypass graft were 14 patients of single vessel graft, 21 patients of two vessels graft, 10 patients of three vessels graft and 3 patients of four vessels graft. CONCLUSION: The hospital operation mortality rate of congenital acyanotic, cyanotic and acquired heart diseases were 2.0%, 15.5%, and 5.1% respectively. The overall mortality rate was 3.6% (72/2,000).
Age Distribution ; Aortic Aneurysm ; Aortic Valve ; Busan ; Coronary Artery Bypass ; Dilatation, Pathologic ; Endocardial Cushion Defects ; Heart Defects, Congenital ; Heart Diseases ; Heart Neoplasms ; Heart Septal Defects, Atrial ; Heart Septal Defects, Ventricular ; Heart Valve Diseases ; Heart Ventricles ; Heart* ; Hospital Mortality ; Humans ; Mitral Valve ; Mortality ; Myocardial Ischemia ; Pulmonary Valve Stenosis ; Rupture ; Sinus of Valsalva ; Tetralogy of Fallot ; Thoracic Surgery* ; Transplants ; Transposition of Great Vessels ; Tricuspid Valve