BACKGROUND: Cholesterol is a major component of specialized membrane microdomains known as lipid rafts or caveolae, which modulate the fluidity of biological membranes. Membrane cholesterol therefore plays an important role in cell signaling and vesicular transport. OBJECTIVE: In this study, we investigated the effects of cholesterol on matrix metalloproteinase-1 (MMP-1) expression in human dermal fibroblasts. METHODS: MMP-1 mRNA and protein expression were determined by RT-PCR and Western blotting, respectively. AP-1 DNA binding activity was detected by electrophoretic mobility shift assays. The amount of cholesterol was analyzed by cholesterol assay kit. RESULTS: We observed that MMP-1 mRNA and protein expression was dose-dependently decreased by cholesterol treatment. In contrast, cholesterol depletion by a cholesterol depletion agent, methyl-beta-cyclodextrin (M beta CD) in human dermal fibroblasts, increased MMP-1 mRNA and protein expression in a dose-dependent manner. Also, we investigated the regulatory mechanism of M beta CD-induced MMP-1 expression: cholesterol depletion by M beta CD, activated ERK1/2 and JNK, but not p38 MAPK cascade, and it also significantly increased c-Jun phosphorylation, c-Fos expression and activator protein-1 binding activity. Furthermore, the inhibition of ERK or JNK with specific chemical inhibitors prevented M beta CD-induced MMP-1 expression, which indicates that ERK and JNK play an important role in cholesterol depletion-mediated MMP-1 induction. In addition, M beta CD-induced phosphorylation of ERK and JNK and MMP-1 expression were suppressed by cholesterol repletion. CONCLUSION: Our results suggest that cholesterol regulates MMP-1 expression through the control of ERK and JNK activity in human dermal fibroblasts.
beta-Cyclodextrins ; Blotting, Western ; Caveolae ; Cholesterol ; DNA ; Electrophoretic Mobility Shift Assay ; Fibroblasts ; Humans ; Matrix Metalloproteinase 1 ; Membrane Microdomains ; Membranes ; p38 Mitogen-Activated Protein Kinases ; Phosphorylation ; RNA, Messenger ; Transcription Factor AP-1

No abstract available.
Coronary Artery Bypass, Off-Pump* ; Endarterectomy, Carotid* ; Hematoma* ; Transplants*

Larger animal models, such as porcine, have been validated as appropriate models of the human disc with respect to biomechanics and biochemistry. They are advantageous for research as the models are relatively straightforward to prepare and easily obtainable for research to perform surgical techniques. The intention of this study was to quantitatively analyze gene expression for collagen and proteoglycan components of the extracellular matrix and for collagenase (MMP-1) in porcine discs of varying ages (Newborn; 2-3weeks, Mature; 6-9 month, Older; 2-3 years). In this study, we observed that the cell number and GAG (glycosaminoglycan) formation dramatically decreased with aging. Also, gene expression in the annulus fibrosus (AF) and nucleus pulposus (NP) cells changed with aging. The level of MMP-1 mRNA increased with age and both type I, II collagens decreased with age. The level of aggrecan mRNA was highest in the mature group and decreased significantly with aging. In the mature group, MMP-1 expression was minimal compared to the newborn group. In AF cells, type II collagen was expressed at a high level in the mature group with a higher level of aggrecan, when aged NP showed a decrease in type II collagen. The model of IVD degeneration in the porcine disc shows many changes in gene expression with age that have been previously documented for human and may serve as a model for studying changes in IVD metabolism with age. We concluded that the porcine model is excellent to test hypotheses related to disc degeneration while permitting time-course study in biologically active systems.
Age Factors ; Aggrecans/genetics/metabolism ; Aging/genetics/*metabolism ; Animals ; Animals, Newborn ; Collagen Type I/genetics/metabolism ; Collagen Type II/genetics/metabolism ; Glycosaminoglycans/genetics/metabolism ; Humans ; Intervertebral Disk Degeneration/genetics/*metabolism ; Matrix Metalloproteinase 1/genetics/*metabolism ; *Models, Animal ; Reverse Transcriptase Polymerase Chain Reaction ; Spinal Cord/*metabolism/pathology ; Swine

With the growing number of patients undergoing left ventricular assist device (LVAD) implantation and improved survival in this population, more patients with LVADs are presenting for various types of non-cardiac surgery. Therefore, anesthesiologists need to understand the physiology and adequately prepare for the perioperative management of this unique patient population. This review addresses perioperative considerations and intraoperative management for the safe and successful management of patients with an LVAD undergoing non-cardiac surgery. Understanding the basic physiology of preload dependency and afterload sensitivity in these patients is essential. The main considerations include a collaborative preoperative multidisciplinary approach, perioperative care aimed at optimizing the intravascular volume and right ventricular function, and maintaining the afterload within recommended ranges for optimal LVAD function.

BACKGROUND: Amlodipine is a third-generation dihydropyridine calcium channel blocker, which has proven to be a useful drug against hypertension or angina. METHODS: This randomized, open-label, two-period, two-treatment, single-dose, crossover study was conducted in twenty healthy male volunteers. Subjects were administered 5 mg of the test or reference formulation. After 2-week washout period, the other formulation was administered. Blood samples were collected up to 144 hours after drug administration, and plasma amlodipine concentrations were determined by validated liquid chromatography-tandem mass spectrometry. Drug safety was assessed using measurement of vital signs, physical examinations, laboratory test, electrocardiograms, and adverse event monitoring. RESULTS: All subjects were completed this study. The geometric mean ratios of Cmax and AUClast were 1.078 (90 % CI, 0.968 - 1.200) and 1.095 (90 % CI, 1.011 - 1.186), respectively. There were no serious adverse events were reported by both formulations. CONCLUSION: This study showed the test and reference formulations had similar pharmacokinetics and safety profiles.
Amlodipine ; Calcium Channels ; Cross-Over Studies ; Electrocardiography ; Healthy Volunteers ; Humans ; Hypertension ; Male* ; Mass Spectrometry ; Pharmacokinetics ; Physical Examination ; Plasma ; Vital Signs

Anesthesia for a patient with a large mediastinal mass is a challenge for anesthesiologists, given the risk of airway collapse and hemodynamic compromise. Moreover, there are very few reports on the anesthetic management of non-intubated video-assisted thoracoscopic surgery (VATS). Thus, in the following case report, we provide an account of the successful anesthetic management and excisional biopsy of a large anterior mediastinal mass (measuring 13 × 10 cm) utilizing non-intubated VATS. The patient was kept awake, maintaining consciousness and spontaneous respiration throughout the procedure, in order to prevent devastating airway collapse and pain control and cough prevention were achieved by thoracic epidural analgesia and lidocaine nebulization.
Analgesia, Epidural ; Anesthesia ; Anesthesia, Epidural* ; Biopsy* ; Consciousness ; Cough ; Hemodynamics ; Humans ; Lidocaine ; Respiration ; Thoracic Surgery, Video-Assisted

PURPOSE: Susceptibility vessel sign (SVS) on gradient echo image, which is caused by MR signal loss due to arterial thrombosis, has been reported in acute middle cerebral artery (MCA) infarction. However, the reported sensitivity and diagnostic accuracy of SVS have been variable. Susceptibility-weighted imaging (SWI) is a newly developed MR sequence. Recent studies have found that SWI may be useful in the field of cerebrovascular diseases, especially for detecting the presence of prominent veins, microbleeds and the SVS. The purpose of this study was to evaluate the diagnostic values of SWI for the detection of hyperacute MCA occlusion. MATERIALS AND METHODS: Sixty-nine patients (37 males, 32 females; 46-89 years old [mean, 69.1]) with acute stroke involving the MCA territory underwent MR imaging within 6 hours after the symptom onset. MR examination included T2, FLAIR (fluid-attenuated inversion recovery), DWI, SWI, PWI (perfusion-weighted imaging), contrast-enhanced MR angiography (MRA) and contrast-enhanced T1. Of these patients, 28 patients also underwent digital subtraction angiography (DSA) within 2 hours after MR examination. Presence or absence of SVS on SWI was assessed without knowledge of clinical, DSA and other MR imaging findings. RESULTS: On MRA or DSA, 34 patients (49.3%) showed MCA occlusion. Of these patients, SVS was detected in 30 (88.2%) on SWI. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of SWI were 88.2%, 97.1%, 96.8%, 89.5% and 92.8%, respectively. CONCLUSION: SWI was sensitive, specific and accurate for the detection of hyperacute MCA occlusion.
Angiography ; Angiography, Digital Subtraction ; Cerebrovascular Disorders ; Female ; Humans ; Infarction ; Magnetic Resonance Imaging* ; Male ; Middle Cerebral Artery ; Sensitivity and Specificity ; Stroke ; Thrombosis ; Veins

Occult breast cancer is a type of breast cancer without any symptoms on the breasts or any abnormalities upon radiologic examination such as mammography. In males, there are few cases of breast cancer, the rate of diagnosis of occult breast cancer is very low, and little is known about this disease. We experienced two cases of occult breast cancers manifesting as axillary lymph node metastasis in men. They had a palpable lesion on axillary area several years ago and had not seen a doctor about it. As such there was no abnormality on evaluations for cancer except for axillary lymph node showing signs of carcinoma (primary or metastatic) on biopsy and estrogen receptor-positive and progesterone receptor-positive on immunohistochemistry. The patients were diagnosed with occult breast cancer, and treatments were performed. Herein, we report the rare cases of occult breast cancers in men.
Axilla ; Biopsy ; Breast ; Breast Neoplasms ; Estrogens ; Humans ; Immunohistochemistry ; Lymph Nodes ; Male ; Mammography ; Neoplasm Metastasis ; Neoplasms, Unknown Primary ; Progesterone

Because of insufficient number of donor hearts for cardiac transplantation, the use of implantable left ventricular assist device (LVAD) has been increasing as an alternative. During this procedure, the fundamental role of anesthesiologists would be to maintain stable hemodynamics. This report describes the anesthetic case of a 75-year-old man who underwent implantable LVAD placement as a destination therapy of his heart failure in Korea. The procedure and anesthesia were uneventful with transesophageal echocariographic guide. He moved to the ward on postoperative day 10 without fatal complication.
Aged ; Anesthesia ; Echocardiography, Transesophageal ; Heart ; Heart Failure ; Heart Transplantation ; Heart-Assist Devices* ; Hemodynamics ; Humans ; Korea ; Tissue Donors

Aortic dissection during pregnancy is a devastating event for both the pregnant woman and the baby. We report a case of acute aortic dissection (Stanford type A) in a pregnant woman with Marfan syndrome at the 29th week of gestation. She underwent a cesarean section followed by an ascending aorta and total arch replacement with cardiopulmonary bypass, without a prior sternotomy. The hemodynamic parameters were kept stable during the cesarean section by using inotropes and vasopressors under transesophageal echocardiography monitoring. The newborn survived after endotracheal intubation and management in a neonatal intensive care unit.
Aorta ; Cardiopulmonary Bypass ; Cesarean Section ; Echocardiography ; Echocardiography, Transesophageal ; Female ; Hemodynamics ; Humans ; Infant, Newborn ; Intensive Care, Neonatal ; Intubation, Intratracheal ; Marfan Syndrome* ; Pregnancy* ; Pregnant Women ; Sternotomy