PURPOSE: Idoxifene is currently entering phase II clinical trials for the treatment of advanced breast cancer. The radiolabeled idoxifene using 123I provides an opportunity for clinical pharmacology with single photon emission computed tomography (SPECT). The purpose of this study was to prepare radiolabeled idoxifene using 123I and to determine its cell uptake of breast cancer cell line. MATERIALS AND METHODS: With a view to evaluating new anticancer drugs, we are investigating the novel antiestrogen pyrrolidino- 4-iodotamoxifen (idoxifene). [123I]Idoxifene has been prepared in no-carrier-added form using a tributyl stannylated precursor which has been synthesized by means of (2-chloroethoxy)benzene with (+/-)-2- phenylbutanoic acid on the basis of previously reported standard methods. The biodistribution and dynamic behavior of the compound were investigated using the comparative breast cancer cell line, MCF-7 (estrogen receptor-positive) and MDA-MB-468 (non-estrogen receptor). RESULTS AND CONCLUSION: Acylation of (2-chloroethoxy)benzene with (+/-)-2-phenylbutanoic acid gave the versatile ketone (81%) which reacted with 1,4-diiodobenzene to give triphenylethylene as a mixture of E and Z geometric isomers, which were separated by the recrystallization in ethanol. The E-isomer was treated with pyrrolidine to give idoxifene (67%). In order to incorporate radioactive iodine into the 4-position, the 4-stannylated precursor was prepared (30%). The yield of radioiodination was 90-92% with a high radiochemical purity greater than 98%. The ratio of tumor uptake of the breast cancer cell line between MCF-7 and MDA-MB-468 was about 1.7.
Acylation ; Breast Neoplasms* ; Breast* ; Cell Line ; Estrogen Receptor Modulators ; Ethanol ; Iodine ; Pharmacology, Clinical ; Tomography, Emission-Computed, Single-Photon

No abstract available.
Atrial Natriuretic Factor* ; Humans* ; Lymph Nodes* ; Polymerase Chain Reaction*

A Morel-Lavallée lesion is a posttraumatic, closed internal degloving injury caused by shearing force abruptly separating the skin and superficial fascia from the deep fascia and creating a potential space. Blood, lymphatic fluid, and debris collect and fill the space. The most commonly affected sites are the thigh, knee, hip, and pelvic area, but the lesion can occur anywhere in the body. Among various treatments, surgical procedure is a good option if the lesion is chronic and a thick peripheral capsule has developed. We report an uncommon case of a chronic Morel-Lavallée lesion in the sacrococcygeal area, a rarely reported location, with an associated coccygeal fracture and dislocation.
Coccyx ; Dislocations ; Fascia ; Hip ; Knee ; Skin ; Subcutaneous Tissue ; Thigh

OBJECTIVES: Due to the heterogeneous receptor distribution and changes of receptor status over time, the biochemical measurement of estrogen receptor status of biopsy specimens is not sufficient to diagnose breast cancer. As a result, I-123 labeled estradiols have been applied for the diagnosis. The purpose of this study was to develop a suitable radioligand for imaging estrogen receptor-positive human breast tumors. METHODS: Among the various estradiol derivatives, 17alpha-[123I]iodovinyl estradiol ([123I]IVE) has been prepared from 17alpha-ethynyl estradiol. Labeling of E-17alpha-[123I]iodovinyl estradiol (E-[123I]IVE) was carried out using peracetic acid with [123I]NaI and Z-[123I]IVE labelling was archived using chloamine- T/HCl solution with [123I]NaI. Labeling yield was determined by silica thin-layer chromatography (TLC) and radiochemical purity was measured by high performance liquid chromatography (HPLC). The biodistribution of E-[123I]IVE was measured in immature female rats at 60 min, 120 min and 300 min after injection. RESULTS: The labeling yield of two isomers was 92% and 94% (E-[123I]IVE and Z-[123I]IVE, respectively). The radiochemical purity was more than 98% after purification. The highest uptake was observed at 120 min in uterus (3.11% ID/g for E-[123I]IVE). CONCLUSION: These results suggest the possibility of using E-[123I]IVE as an imaging agent for the evaluation of the presence of estrogen receptor in patients with breast cancer.
Animals ; Biopsy ; Breast Neoplasms ; Chromatography, Liquid ; Chromatography, Thin Layer ; Diagnosis ; Estradiol* ; Estrogens ; Female ; Humans ; Peracetic Acid ; Rats ; Silicon Dioxide ; Uterus

BACKGROUND AND OBJECTIVES: ovastatin, a HMG-CoA reductase inhibitor, is known to show antiproliferative effects on VSMC after vessel injury, but a large amount of the drug is needed orally for this purpose. This study investigated the effects of lovastatin given locally to injured carotid arteries of rats on reducing neointimal hyperplasia. MATERIALS AND METHOD: Lovastatin was given perivascularly to balloon-injured carotid arteries of 21 rats in 1 microM to the low-dose group, and 30 microM to the high-dose group. The control group was treated with pluronic gel only. Two weeks later, the lumen area, neointimal areas and the number of actively proliferating cells were obtained and compared. RESULTS: eointimal area was 0.113+/-0.032 mm2, 0.065+/-0.017 mm2, 0.072+/-0.017 mm2 in the control, low-dose and high-dose groups respectively. The area was significantly smaller in the treatment groups (p<0.05), but no significant difference was observed between the treatment groups. The number of actively proliferating cells per mm2 of neointimal area were 714.5+/-227.4, 688.4+/-333.7, and 1526.3+/-744.0 in the groups respectively, and the number was significantly high in the high-dose group (p<0.05). CONCLUSION: Local administration of lovastatin is effective in reducing neointimal hyperplasia after vascular injury, but extremely high doses are not needed locally for this purpose.
Animals ; Carotid Arteries* ; Carotid Artery Injuries* ; Hyperplasia* ; Lovastatin* ; Oxidoreductases ; Rats* ; Vascular System Injuries

BACKGROUND AND OBJECTIVES: Heart rate variability(HRV) reflects the autonomic integration of heart. There were many reports that HRV in patients with myocardial infarction or heart failure is an independent prognostic factor to predict fatal arrhythmia and sudden cardiac death. But, the role of HRV is still controversial in stable angina patients without history of myocardial infarction. In this study, we tried to compare HRV indices between stable angina patients and normal subjects. MATERIALS AND METHODS: Twenty-one stable anginal patients without history of myocardial infarction (mean age : 57 +/- 2 years) and twenty-one relatively healthy persons without history of coronary heart disease (mean age : 53 +/- 2 years) were included in the study and underwent 24-hour ambulatory ECG monitoring. In patients group, all underwent coronary angiography after 24-hour ambulatory ECG monitoring. HRV was analyzed over the whole 24 hours, using time and frequency domain parameters, according to time phases and coronary angiographic severity. RESULTS: There were no significant differences in age, sex and cardiovascular risk factors, except hypertension (p=.001) between two groups. HRV indices such as rMSSD, pNN50, LF, HF, LFnorm and HFnorm were significantly decreased (p<0.05) in patients group. But the angiographic severity of coronary arteries did not show any significant effect on the HRV indices in patients group. CONCLUSIONS: We observed significantly reduced HRV indices in patients with stable angina without history of myocardial infarction.
Angina, Stable* ; Arrhythmias, Cardiac ; Coronary Angiography ; Coronary Disease ; Coronary Vessels ; Death, Sudden, Cardiac ; Electrocardiography ; Heart Failure ; Heart Rate* ; Heart* ; Humans ; Hypertension ; Myocardial Infarction* ; Risk Factors

BACKGROUND AND OBJECTIVES: This study was performed to investigate the antiproliferative effect of lovastatin on vascular smooth muscle cell, especially to determine whether lovastatin induces apoptosis in vascular smooth muscle cell and the products of mevalonate pathway can reverse the antiproliferative effect of lovastatin. METHODS AND MATERIALS: Lovastatin only and lovastatin with one of the products of mevalonate pathway such as isopentenyl adenine, farnesol, mevalonate, cholesterol were added respectively in cultured rat vascular smooth muscle cells stimulated with 10% fetal calf serum. DNA synthesis was measured by tritiated-thymidine incorporation. Cell number was determined by hemocytometric counting. Cells were Giemsa-stained to evaluate morphological changes of apoptosis. Extracted DNA from the cells treated with lovastatin was assessed by gel electrophoresis. RESULTS: 1)Lovastatin inhibited DNA synthesis and cell proliferation in a dose-dependent manner. 2)The inhibitory effects of lovastatin could be reversed almost completely by mevalonate, partially by farnesol. 3)Lovastatin-treated vascular smooth muscle cells showed typical morphological changes of apoptosis. 4)A distinct ladder of DNA bands was visualized by gel electrophoresis of the DNA from the cells treated with lovastatin. CONCLUSION: Mevalonate metabolism is essential for vascular smooth muscle cell proliferation. The antiproliferative effect of lovastatin may result from the induction of apoptosis in vascular smooth muscle cells.
Adenine ; Animals ; Apoptosis ; Cell Count ; Cell Proliferation ; Cholesterol ; DNA ; Electrophoresis ; Farnesol ; Lovastatin* ; Metabolism ; Mevalonic Acid ; Muscle, Smooth, Vascular* ; Rats

BACKGROUND AND OBJECTIVES: Neurocardiogenic syncope is believed to be caused by a transient imbalance of autonomic nervous system. Actually, there were significant differences in heart rate variability (HRV) indices during head-up tilt test between patients with neurocardiogenic syncope and normal controls. But there was no definite evidence for it during daily activity. So, we tried to evaluate HRV during daily activity with 24-hour ambulatory electrocardiography monitoring. MATERIALS AND METHODS: 27 patients with neurocardiogenic syncope or presyncope (mean age 45+/-3) and 25 normal volunteers (mean age 47+/-2) comparable for age and sex underwent 24-hour ambulatory electrocardiography. Head-up tilt test was used to diagnose neurocardiogenic syncope or presyncope in patients group. HRV was analysed over the whole 24 hours, using time and frequency domain parameters. Student's t-test was applied. ResultsThere were no significant differences in HRV measures between two groups, over 24-hour period and day-time and night-time period. But the hourly HRV measures showed a transient decrease of LF, LFnorm and LF/HF ratio in patients group compared to normal control group. CONCLUSIONS: These results indicate that patients with neurocardiogenic syncope or presyncope suffer from temporarily decreased sympathetic tone with normal parasympathetic tone. So, transient additive change of autonomic nervous tone may cause syncope or presyncope in these patients. (Korean Circulation J 2000;30 (6):716-723)
Autonomic Nervous System ; Electrocardiography, Ambulatory ; Healthy Volunteers ; Heart Rate* ; Heart* ; Humans ; Syncope* ; Syncope, Vasovagal*

BACKGROUND: It has been suggested that all components of the renin-angiotensin-aldosterone system (RAAS) are present in the vascular wall and that the vascular RAAS modulates vascular tone and vascular hypertrophy. One of the catalytic step in the RAAS cascade is the local conversion of angiotensin I to angiotensin II (Ang II) by angiotensin converting enzyme (ACE). One of the major sources of ACE in the vasculature is vascular smooth muscle cells (VSMC). Here, we provide insight into the intrinsic mechanisms by which the components of RAAS regulate gene expression of ACE in cultured smooth muscle cells of the rat and we also investigated the effects of cytokines on ACE mRNA. METHODS: RNA was extracted from the primary cultured VSMCs. We analyzed the expression levels of ACE by competitive reverse transcription-PCR using recombinant RNA as an internal standard. RESULTS: 1) ACE mRNA level was increased markedly by aldosterone in a dose- and time-dependent manner, indicating that there exists positive feedback mechanism within RAAS. 2) The induction of ACE mRNA by aldosterone was inhibited by spironolactone. 3) Aldosterone-stimulated expression of ACE was also inhibited by Ang II, which shows that Ang II acts as a negative regulator of the expression of ACE in RAAS cascade. 4) Interleukin-1beta or TNF-alpha did not induce ACE mRNA expression. 5) However, mixture of interleukin-1betaand TNF-alpha(CytoMix) significantly increased the expression of ACE. It was also shown that CytoMix increased aldosterone-stimulated ACE mRNA expression in an additative manner. CONCLUSION: These results indicate that the expression of ACE in smooth muscle cells is modulated by the components of RAAS and cytokines. The intrinsic positive and negative feedback controls of RAAS would play an important role in the pathogenesis of vascular diseases.
Aldosterone* ; Angiotensin I ; Angiotensin II ; Angiotensins* ; Animals ; Cytokines* ; Gene Expression ; Hypertrophy ; Interleukin-1beta ; Muscle, Smooth, Vascular* ; Myocytes, Smooth Muscle ; Peptidyl-Dipeptidase A* ; Rats ; Renin-Angiotensin System ; RNA ; RNA, Messenger ; Spironolactone ; Tumor Necrosis Factor-alpha* ; Vascular Diseases

Coronary arteriovenous malformation (AVM) is a rare congenital coronary anomaly. We report a 60 year-old woman with variant angina and coronary AVM. She presented with recurrent chest pain at rest but there were no significant cardiovascular risk factors. Baseline coronary angiography showed the AVM which originated from first diagonal branch. Acetylcholine (Ach) provocation test was performed at left anterior descending artery (LAD) to induce coronary spasm. Ach 50 microgram injection induced severe diffuse spasm at LAD with typical chest pain. We confirmed that this patient has variant angina with AV malformation.
Acetylcholine ; Arteries ; Arteriovenous Malformations* ; Chest Pain ; Coronary Angiography ; Female ; Humans ; Middle Aged ; Risk Factors ; Spasm