This study aimed to investigate the analgesic effect of substance P (SP) in an animal model of neuropathic pain. An experimental model of neuropathic pain, the chronic constriction injury (CCI) model, was established using ICR mice. An intravenous (i.v.) injection of SP (1 nmole/kg) was administered to the mice to examine the analgesic effects of systemic SP on neuropathic pain. Behavioral testing and immunostaining was performed following treatment of the CCI model with SP. SP attenuated mechanical allodynia in a time-dependent manner, beginning at 1 h following administration, peaking at 1 day post-injection, and decaying by 3 days post-injection. The second injection of SP also increased the threshold of mechanical allodynia, with the effects peaking on day 1 and decaying by day 3. A reduction in phospho-ERK and glial fibrillary acidic protein (GFAP) accompanied the attenuation of mechanical allodynia. We have shown for the first time that i.v. administration of substance P attenuated mechanical allodynia in the maintenance phase of neuropathic pain using von Frey’s test, and simultaneously reduced levels of phospho-ERK and GFAP, which are representative biochemical markers of neuropathic pain. Importantly, glial cells in the dorsal horn of the spinal cord (L4–L5) of SP-treated CCI mice, expressed the anti-inflammatory cytokine, IL-10, which was not seen in vehicle saline-treated mice. Thus, i.v. administration of substance P may be beneficial for improving the treatment of patients with neuropathic pain, since it decreases the activity of nociceptive factors and increases the expression of anti-nociceptive factors.
Administration, Intravenous* ; Animals ; Behavior Rating Scale ; Biomarkers ; Constriction ; Glial Fibrillary Acidic Protein ; Humans ; Hyperalgesia* ; Interleukin-10 ; Mice ; Mice, Inbred ICR ; Models, Animal ; Models, Theoretical ; Neuralgia ; Neuroglia ; Spinal Cord ; Spinal Cord Dorsal Horn ; Substance P*

In this study, we aim to determine the in vivo effect of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) on neuropathic pain, using three, principal peripheral neuropathic pain models. Four weeks after hUCB-MSC transplantation, we observed significant antinociceptive effect in hUCB-MSC–transplanted rats compared to that in the vehicle-treated control. Spinal cord cells positive for c-fos, CGRP, p-ERK, p-p 38, MMP-9 and MMP 2 were significantly decreased in only CCI model of hUCB-MSCs-grafted rats, while spinal cord cells positive for CGRP, p-ERK and MMP-2 significantly decreased in SNL model of hUCB-MSCs-grafted rats and spinal cord cells positive for CGRP and MMP-2 significantly decreased in SNI model of hUCB-MSCs-grafted rats, compared to the control 4 weeks or 8weeks after transplantation (p<0.05). However, cells positive for TIMP-2, an endogenous tissue inhibitor of MMP-2, were significantly increased in SNL and SNI models of hUCB-MSCs-grafted rats. Taken together, subcutaneous injection of hUCB-MSCs may have an antinociceptive effect via modulation of pain signaling during pain signal processing within the nervous system, especially for CCI model. Thus, subcutaneous administration of hUCB-MSCs might be beneficial for improving those patients suffering from neuropathic pain by decreasing neuropathic pain activation factors, while increasing neuropathic pain inhibition factor.
Animals ; Cord Blood Stem Cell Transplantation ; Humans* ; Injections, Subcutaneous ; Multipotent Stem Cells* ; Nervous System ; Neuralgia* ; Rats* ; Spinal Cord ; Tissue Inhibitor of Metalloproteinase-2 ; Umbilical Cord*

PURPOSE: The purpose of this study was to determine the underestimation rate of ductal carcinoma in situ (DCIS) on sonographically guided 14-gauge core needle biopsy of the breast and to investigate the factors associated with this underestimation. MATERIALS AND METHODS: We retrospectively reviewed 2990 consecutive lesions that underwent sonographically guided 14-gauge core needle biopsy between January 2005 and December 2008. Among them, 61 lesions were pathologically proven to be DCIS (2.04%). A total of 50 DCIS lesions (mean patient age: 50.7 years old, age range: 36-79 years old) that underwent surgical resection were included in this study. After surgery, the lesion proven to be invasive was defined as being in the underestimated group and the lesion proven to DCIS was defined as being in the correctly diagnosed group. We determined the underestimation rate of DCIS and we retrospectively reviewed and compared the clinical, pathologic and radiologic features of the two groups. RESULTS: The underestimation rate of DCIS was found to be 28% (14 of 50 lesions). The underestimation of DCIS was significantly frequent for a clinically palpable lesion (78.6% (11/14) vs. 30.5% (11/36), respectively, p = 0.002). The sonographically maximal diameter of a lesion was significantly larger in the underestimated group than that in the accurately diagnosed group (28.4 +/- 14.0 mm vs. 17.6 +/- 10.3 mm, respectively, p = 0.017) and underestimation was significantly frequent when the sonographic lesion size was > 20 mm (p = 0.012). There was no significant difference in terms of age, the lesion type, the Breast Imaging-Reporting and Data System (BI-RADS) category or the pathologic features between the two groups. CONCLUSION: The underestimation rate of DCIS was 28% for sonographically guided 14-gauge core needle biopsy of the breast. Clinical symptoms such as a palpable lesion and a sonographic lesion size > 20 mm were the factors related with the underestimation of DCIS.
Biopsy, Large-Core Needle ; Breast ; Carcinoma, Ductal ; Carcinoma, Intraductal, Noninfiltrating ; Humans ; Information Systems ; Retrospective Studies

Ganglion cysts are common lesions that are most often found around the hands and feet. Ganglia around the proximal tibiofibular joint usually occur within the synovial membrane, tendon sheath or peroneal nerve, but they rarely occur within muscle. We report here on a case of a 60-year-old man who complained of an asymptomatic deep seated mass in the proximal part of the right calf that he'd had for more than two years. On magnetic resonance imaging, the lesion appeared as a cystic lesion within the gastrocnemius muscle without communication with the knee joint. To the best of our knowledge, intramuscular ganglion cyst has never been reported in the Korean dermatologic literature.
Foot ; Ganglia ; Ganglion Cysts ; Hand ; Humans ; Joints ; Knee Joint ; Magnetic Resonance Imaging ; Middle Aged ; Muscle, Skeletal ; Muscles ; Peroneal Nerve ; Synovial Membrane ; Tendons

Loeys-Dietz Syndrome (LDS) is a recently described autosomal dominant aortic aneurysm syndrome with widespread systemic involvement. It is characterized by the triad of 1) arterial tortuosity and aneurysms, 2) hypertelorism, and 3) bifid uvula or cleft palate. A 12-year-old boy with LDS was scheduled to undergo correction of aortic valve regurgitation due to aortic annuloectasia. We report our clinical experiences of a case of LDS patient with brief review of related literatures and relevant anesthetic problems.
Aneurysm ; Aortic Aneurysm ; Aortic Valve ; Arteries ; Child ; Cleft Palate ; Humans ; Hypertelorism ; Joint Instability ; Loeys-Dietz Syndrome ; Skin Diseases, Genetic ; Uvula ; Vascular Malformations

Ascorbic Acid ; Bone Development ; Bone Marrow ; Dexamethasone ; Durapatite ; Fractures, Bone ; Gene Expression ; Glycerophosphates ; Humans ; Neuropilin-1 ; Osteoblasts ; Osteocalcin ; Osteogenesis ; Phenotype ; Protein Isoforms ; Receptors, Vascular Endothelial Growth Factor ; Stromal Cells ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor Receptor-1 ; Vascular Endothelial Growth Factor Receptor-2

PURPOSE: We wanted to evaluate the safety and effectiveness of superselective transarterial embolization for the management of gastrointestinal bleeding. MATERIALS AND METHODS: We evaluated 97 of 115 patients who had undergone diagnostic angiography and transarterial embolization for gastrointestinal bleeding from February 2001 to July 2004, and they subsequently underwent superselective transarterial embolization. Their ages ranged from 17 to 88 years (mean age: 58.5 years), and 73 were men and 24 were women. The etiologies were a postoperative condition (n=31), ulcer (n=23), Mallory-Weiss syndrome (n=3), trauma (n=3), pseudoaneurysm from pancreatitis (n=3), diverticula (n=2), inflammatory bowel disease (n=2), tumor (n=2), Behcet's disease (n=2), hemobilia (n=1), and unknown origin (n=25). The regions of bleeding were the esophagus (n=3), stomach and duodenum (n=41), small bowel (n=38) and colon (n=15). All the patients underwent superselective transarterial embolization using microcoils, gelfoam or a combination of microcoils and gelfoam. Technical success was defined as devascularization of targeted vascular lesion or the disappearance of extravasation of the contrast media, as noted on the angiography after embolization. Clinical success was defined as the disappearance of clinical symptoms and the reestablishment of normal cardiovascular hemodynamics after transarterial embolization without any operation or endoscopic management. RESULTS: The technical success rate was 100%. The primary clinical success rate was 67% (65 of 97 patients). Of the 32 primary failures, fourteen patients underwent repeat embolization; of these, clinical success was achieved in all the patients and so the secondary clinical success rate was 81% (79 of 97 patients). Of the 18 patients with primary failures, five patients underwent operation, one patient underwent endoscopic management and the others died during the observation period due to disseminated coagulopathy or complications of their underlying diseases. During the follow up period, six patients of the 79 clinically successful patients died due to disseminated coagulopathy or complications of their underlying diseases, and so the total mortality rate was 19% (18 of 97 patients). Postembolization complications such as bowel ischemia or infarction did not occur during the observation period. CONCLUSION: Superselective transarterial embolization is an effective therapy for treating acute gastrointestinal hemorrhage, and it has a high technical rate and clinical success rate, and a low complication rate.
Aneurysm, False ; Angiography ; Colon ; Contrast Media ; Diverticulum ; Duodenum ; Esophagus ; Female ; Follow-Up Studies ; Gastrointestinal Hemorrhage ; Gelatin Sponge, Absorbable ; Hemobilia ; Hemodynamics ; Hemorrhage* ; Humans ; Infarction ; Inflammatory Bowel Diseases ; Ischemia ; Male ; Mallory-Weiss Syndrome ; Mortality ; Pancreatitis ; Stomach ; Ulcer

PURPOSE: The aim of this study was to determine a safe gastrointestinal contrast agent that could be used in various clinical situations where there is a risk of aspiration using a rabbit model. MATERIALS AND METHODS: 30 healthy white rabbits were used. The rabbits were divided into 5 groups containing six animals each, one control group (anesthesia only) and 4 groups receiving various contrast agents [Solotop (Barium sulphate suspension), Gastrografin (Sodium and meglumine amidotrizoate), and Telebrix (Meglumine ioxitalamate), Visipaque (Iodixanol)]. The contrast agents were injected selectively into a main bronchus via a catheter inserted under fluoroscopy guidance. The rabbits were sacrificed either 1 day or 7 days after injecting the contrast agents, and the tissue reaction of the bronchi and lungs were examined both macro- and microscopically. The level of alveolar septal thickening, peribronchiolar lymphocytic infiltration, pulmonary congestion and edema, inflammatory exudate in the alveoli or bronchiolar lumina, microabscess formation, necrosis, pigmentation of materials injected, and fibropurulent pleurisy were evaluated and graded according to the severity as follows: no change, mild, moderate, marked in degree. RESULTS: The common microscopic findings were alveolar septal thickening and peribronchiolar lymphocytic infiltration. Pulmonary congestion and edema, inflammatory exudate in the alveoli or bronchiolar lumina were observed in 21 out of 24 rabbits receiving the contrast agents. Pigmentation of the materials injected was observed only in the group receiving Solotop. An inflammatory exudate in the alveoli and bronchiolar/bronchial lumina, microabscess formation, and necrosis were noted in most groups, but was more frequent and severe in the group receiving Gastrografin. CONCLUSION: The histopathological reactions of the rabbit lungs after the intrabronchial application of a contrast agent showed variable degrees of inflammatory reactions. Gastrografin produced most severe and extensive reaction, Solotop and Telebrix a moderate reaction, and Visipaque a minimal reaction. Therefore, a non-ionic dimeric contrast agent such as Visipaque may be the safest contrast agent in the lung when a GI tract examination is performed in clinical situations where there is a risk of aspiration.
Animals ; Bronchi ; Catheters ; Contrast Media* ; Diatrizoate Meglumine ; Edema ; Estrogens, Conjugated (USP) ; Exudates and Transudates ; Fluoroscopy ; Gastrointestinal Tract ; Lung* ; Meglumine ; Necrosis ; Pigmentation ; Pleurisy ; Rabbits

PURPOSE: We wanted to evaluate the potential role of dynamic incremental computed tomography (CT) for making the diagnosis of malignant solitary pulmonary nodule (SPN) by investigating the dynamic enhancement patterns. MATERIALS AND METHODS: Forty patients with presumed malignant SPN (diameter < 30 mm) were selected for dynamic incremental chest CT scanning. Histopathologic diagnoses of the malignant SPNs were obtained by surgical excision (n=8) and transthoracic needle biopsy (n=32), and they were squamous cell carcinoma (n=16), adenocarcinoma (n=14), small cell carcinoma (n=5), bronchioloalveolar carcinoma (n=3), and large cell carcinoma (n=2). CT scans were performed at the region of interest (ROI) of the lung nodule before and after contrast enhancement. The dynamic incremental CT scans after contrast enhancement were performed at 15 seconds, 30 seconds, 45 seconds, 60 seconds, 90 seconds, 2 minutes, 3 minutes and 4 minutes. The degree of contrast enhancement according to the time course and the time of maximum enhancement of the malignant nodules were recorded by measuring the Hounsfield Unit (HU) of the nodules at the ROI. We assessed the differences of the contrast enhancement patterns among the histopathologic subtypes of malignant SPN. RESULTS: In malignant SPN, the average time of maximum contrast enhancement was 62.2+/-16.2 seconds, and the average degree of maximum contrast enhancement was 66.4+/-22.17 HU. Most primary lung cancer showed rapid contrast enhancement with slow washout. The differences of the enhancement patterns among the histopathologic subtypes were not statistically significant (p > 0.05). CONCLUSION: Dynamic incremental chest CT was useful for making the diagnosis of malignant SPN that showed an established dynamic contrast enhancement pattern regardless of the histopatholgic subtypes.
Adenocarcinoma ; Adenocarcinoma, Bronchiolo-Alveolar ; Biopsy, Needle ; Carcinoma, Large Cell ; Carcinoma, Small Cell ; Carcinoma, Squamous Cell ; Diagnosis ; Humans ; Lung ; Lung Neoplasms ; Solitary Pulmonary Nodule* ; Tomography, X-Ray Computed

BACKGROUND: It is known that bupivacaine induce cell death in several immortalized cells. However, there is no report concerning bupivacaine-induced cell death in the primary cultured cardiomyocytes. We compared the direct cytotoxicity of local anesthetics in cardiomyocytes. Furthermore, the mechanisms of cell death were evaluated. METHODS: The myocardial cells of rat pups were cultured 3 days after seeding. The methyltetrazolium (MTT) assay was employed to quantify differences in cellular viability. To confirm apoptosis, Hoechst-propidium iodide staining, DNA fragmentation by electrophoresis and western blot analysis were performed. And to examine the mechanisms of cell death, intracellular calcium and expression levels of mitogen-activated protein kinases (MAPKs) family members were evaluated. RESULTS: Among the local anesthetics under 1 mM concentration for 18 h, only bupivacaine significantly decreased the MTT activity (P < 0.001). Bupivacaine induced cell death in a dose-responsive and time dependent manner. Cell death showed apoptotic characteristics, such as DNA fragmentation, chromatin condensation, decrease of precursor caspase-3 protein level, increased cleaved PARP, and cytochrome C release into the cytoplasm. Bupivacaine phosphorylated three major MAPKs, i.e. extracellular signal-regulated kinases (ERKs), p38 kinase and c-Jun N-terminal kinases (JNKs) stress-activated protein kinases. Administration of ERK inhibitor increase cell death, whereas inhibitors of p38 kinase and JNK decreased cell death (P < 0.05). In addition, the intracellular calcium level was approximately 4 times higher after the bupivacaine treatment (P < 0.001), which was inhibited by calcium chelators (P < 0.001). Calcium chelators inhibited expression of MAPKs. CONCLUSIONS: In bupivacaine-induced apoptosis in cardiomyocytes, intracellular calcium increase and MAPKs family plays important roles.
Anesthetics, Local ; Animals ; Apoptosis* ; Blotting, Western ; Bupivacaine ; Calcium ; Caspase 3 ; Cell Death ; Chelating Agents ; Chromatin ; Cytochromes c ; Cytoplasm ; DNA Fragmentation ; Electrophoresis ; Extracellular Signal-Regulated MAP Kinases ; Humans ; Mitogen-Activated Protein Kinases ; Myocytes, Cardiac* ; p38 Mitogen-Activated Protein Kinases* ; Phosphotransferases ; Protein Kinases ; Rats