Vascular endothelial growth factor (VEGF) plays a pivotal role in pathologic ocular neovascularization and vascular leakage via activation of VEGF receptor 2 (VEGFR2). This study was undertaken to evaluate the therapeutic mechanisms and effects of the tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a VEGFR2 inhibitor, in the development of vascular permeability and choroidal neovascularization (CNV). In cultured human retinal microvascular endothelial cells (HRMECs), treatment with RLYE blocked VEGF-A-induced phosphorylation of VEGFR2, Akt, ERK, and endothelial nitric oxide synthase (eNOS), leading to suppression of VEGF-A-mediated hyper-production of NO. Treatment with RLYE also inhibited VEGF-A-stimulated angiogenic processes (migration, proliferation, and tube formation) and the hyperpermeability of HRMECs, in addition to attenuating VEGF-A-induced angiogenesis and vascular permeability in mice. The anti-vascular permeability activity of RLYE was correlated with enhanced stability and positioning of the junction proteins VE-cadherin, β-catenin, claudin-5, and ZO-1, critical components of the cortical actin ring structure and retinal endothelial barrier, at the boundary between HRMECs stimulated with VEGF-A. Furthermore, intravitreally injected RLYE bound to retinal microvascular endothelium and inhibited laser-induced CNV in mice. These findings suggest that RLYE has potential as a therapeutic drug for the treatment of CNV by preventing VEGFR2-mediated vascular leakage and angiogenesis.
Actins ; Animals ; Capillary Permeability ; Choroid ; Choroidal Neovascularization ; Claudin-5 ; Endothelial Cells ; Endothelium ; Humans ; Macular Degeneration ; Mice ; Nitric Oxide Synthase Type III ; Permeability ; Phosphorylation ; Receptors, Vascular Endothelial Growth Factor ; Retinaldehyde ; Vascular Endothelial Growth Factor A

STUDY DESIGN: Retrospective radiographic study. OBJECTIVES: To evaluate the characteristics of concurrent degenerative cervical and lumbar spondylolisthesis. SUMMARY OF LITERATURE REVIEW: Concurrent degenerative cervical and lumbar spondylotic diseases have been reported. Given that severe spondylosis can result in spondylolisthesis, one might expect that concurrent spondylolisthesis of the cervical and lumbar spines might also be prevalent. However, the incidence of spondylolistheses in the lumbar and cervical spines might differ due to anatomical differences between the 2 areas. Nonetheless, there is minimal information in the literature concerning the incidence of concurrent cervical and lumbar spondylolisthesis. MATERIAL AND METHODS: We evaluated standing cervical and lumbar lateral radiographs of 2510 patients with spondylosis. Concurrence, age group, gender, and direction of spondylolisthesis were evaluated. Lumbar spondylolisthesis was defined as at least Meyerding grade I and degenerative cervical spondylolisthesis was defined as over 2 mm of displacement on standing lateral radiographs. RESULTS: Lumbar spondylolisthesis was found in 125 patients (5.0%) and cervical spondylolisthesis was found in 193 patients (7.7%). Seventeen patients had both degenerative cervical and lumbar spondylolistheses (0.7%). Lumbar spondylolisthesis is a risk factor for co-existing cervical spondylolisthesis. Lumbar spondylolisthesis was more common in females than males, independent of advancing age. In contrast, degenerative cervical spondylolisthesis was more common in older patients, independent of gender. Anterolisthesis was more common in the lumbar spine. Retrolisthesis was more common in the cervical spine. CONCLUSIONS: There was a higher prevalence of degenerative cervical spondylolisthesis in patients with degenerative lumbar spondylolisthesis.
Cervical Vertebrae ; Female ; Humans ; Incidence ; Lumbar Vertebrae ; Male ; Prevalence ; Retrospective Studies ; Risk Factors ; Spine ; Spondylolisthesis ; Spondylosis

OBJECTIVES: To evaluate the characteristics of concurrent degenerative cervical and lumbar spondylolisthesis.SUMMARY OF LITERATURE REVIEW: Concurrent degenerative cervical and lumbar spondylotic diseases have been reported. Given that severe spondylosis can result in spondylolisthesis, one might expect that concurrent spondylolisthesis of the cervical and lumbar spines might also be prevalent. However, the incidence of spondylolistheses in the lumbar and cervical spines might differ due to anatomical differences between the 2 areas. Nonetheless, there is minimal information in the literature concerning the incidence of concurrent cervical and lumbar spondylolisthesis.MATERIAL AND METHODS: We evaluated standing cervical and lumbar lateral radiographs of 2510 patients with spondylosis. Concurrence, age group, gender, and direction of spondylolisthesis were evaluated. Lumbar spondylolisthesis was defined as at least Meyerding grade I and degenerative cervical spondylolisthesis was defined as over 2 mm of displacement on standing lateral radiographs. RESULTS: Lumbar spondylolisthesis was found in 125 patients (5.0%) and cervical spondylolisthesis was found in 193 patients (7.7%). Seventeen patients had both degenerative cervical and lumbar spondylolistheses (0.7%). Lumbar spondylolisthesis is a risk factor for co-existing cervical spondylolisthesis. Lumbar spondylolisthesis was more common in females than males, independent of advancing age. In contrast, degenerative cervical spondylolisthesis was more common in older patients, independent of gender. Anterolisthesis was more common in the lumbar spine. Retrolisthesis was more common in the cervical spine. CONCLUSIONS There was a higher prevalence of degenerative cervical spondylolisthesis in patients with degenerative lumbar spondylolisthesis.

A 35-year-old woman visited the emergency department for a pedestrian traffic accident. Severe tenderness was noted at the posterior sacrum area, without open wound or initial neurologic deficit. Fracture of the left sacral ala extended to the S1 foramen, anterior acetabulum, and pubic ramus. Two weeks after the injury, she presented aggravating radiculopathy with the weakness of the left great toe plantar flexion. The S1 nerve root was compressed by the fracture fragments in the left S1 foramen. Decompressive S1 foraminotomy was performed. The postoperative follow-up computed tomography scan showed successful decompression of the encroachment, and the patient recovered well from the radiculopathy with motor weakness. She was able to resume her daily routine activity. We suggest that early decompressive sacral foraminotomy could be a useful additional procedure in selective sacral zone II fractures that are accompanied by radiculopathy with a motor deficit.
Accidents, Traffic ; Acetabulum ; Adult ; Decompression ; Emergency Service, Hospital ; Female ; Follow-Up Studies ; Foraminotomy* ; Humans ; Neurologic Manifestations ; Radiculopathy ; Sacrum ; Toes ; Wounds and Injuries

A 35-year-old woman visited the emergency department for a pedestrian traffic accident. Severe tenderness was noted at the posterior sacrum area, without open wound or initial neurologic deficit. Fracture of the left sacral ala extended to the S1 foramen, anterior acetabulum, and pubic ramus. Two weeks after the injury, she presented aggravating radiculopathy with the weakness of the left great toe plantar flexion. The S1 nerve root was compressed by the fracture fragments in the left S1 foramen. Decompressive S1 foraminotomy was performed. The postoperative follow-up computed tomography scan showed successful decompression of the encroachment, and the patient recovered well from the radiculopathy with motor weakness. She was able to resume her daily routine activity. We suggest that early decompressive sacral foraminotomy could be a useful additional procedure in selective sacral zone II fractures that are accompanied by radiculopathy with a motor deficit.
Accidents, Traffic ; Acetabulum ; Adult ; Decompression ; Emergency Service, Hospital ; Female ; Follow-Up Studies ; Foraminotomy* ; Humans ; Neurologic Manifestations ; Radiculopathy ; Sacrum ; Toes ; Wounds and Injuries

Heme oxygenase-1-derived carbon monoxide prevents inflammatory vascular disorders. To date, there is no clear evidence that HO-1/CO prevents endothelial dysfunction associated with the downregulation of endothelial NO synthesis in human endothelial cells stimulated with TNF-α. Here, we found that the CO-releasing compound CORM-2 prevented TNF-α-mediated decreases in eNOS expression and NO/cGMP production, without affecting eNOS promoter activity, by maintaining the functional activity of the eNOS mRNA 3′-untranslated region. By contrast, CORM-2 inhibited MIR155HG expression and miR-155-5p biogenesis in TNF-α-stimulated endothelial cells, resulting in recovery of the 3′-UTR activity of eNOS mRNA, a target of miR-155-5p. The beneficial effect of CORM-2 was blocked by an NF-κB inhibitor, a miR-155-5p mimic, a HO-1 inhibitor and siRNA against HO-1, indicating that CO rescues TNF-α-induced eNOS downregulation through NF-κB-responsive miR-155-5p expression via HO-1 induction; similar protective effects of ectopic HO-1 expression and bilirubin were observed in endothelial cells treated with TNF-α. Moreover, heme degradation products, except iron and N-acetylcysteine prevented H₂O₂-mediated miR-155-5p biogenesis and eNOS downregulation. These data demonstrate that CO prevents TNF-α-mediated eNOS downregulation by inhibiting redox-sensitive miR-155-5p biogenesis through a positive forward circuit between CO and HO-1 induction. This circuit may play an important preventive role in inflammatory endothelial dysfunction associated with human vascular diseases.
Acetylcysteine ; Bilirubin ; Carbon Monoxide* ; Carbon* ; Down-Regulation* ; Endothelial Cells ; Heme ; Humans ; Iron ; RNA, Messenger ; RNA, Small Interfering ; Vascular Diseases

Concentrations of heavy metals exceed safety thresholds in the soil near Janghang Copper Refinery, a smelter in Korea that operated from 1936 to 1989. This study was conducted to evaluate the level of exposure to toxic metals and the potential effect on health in people living near the smelter. The study included 572 adults living within 4 km of the smelter and compared them with 413 controls group of people living similar lifestyles in a rural area approximately 15 km from the smelter. Urinary arsenic (As) level did not decrease according to the distance from the smelter, regardless of gender and working history in smelters and mines. However, in subjects who had no occupational exposure to toxic metals, blood lead (Pb) and cadmium (Cd) and urinary Cd decreased according to the distance from the smelter, both in men and women. Additionally, the distance from the smelter was a determinant factor for a decrease of As, Pb, and Cd in multiple regression models, respectively. On the other hands, urinary Cd was a risk factor for renal tubular dysfunction in populations living near the smelter. These results suggest that Janghang copper smelter was a main contamination source of As, Pb, and Cd, and populations living near the smelter suffered some adverse health effects as a consequence. The local population should be advised to make efforts to reduce exposure to environmental contaminants, in order to minimize potential health effects, and to pay close attention to any health problems possibly related to toxic metal exposure.
Acetylglucosaminidase/urine ; Adult ; Aged ; Arsenic/*urine ; Bone Density ; Cadmium/*blood ; Case-Control Studies ; Chemical Industry ; Creatinine/urine ; *Environmental Exposure ; Environmental Pollutants/*analysis/blood/urine ; Female ; Humans ; Lead/*blood ; Male ; Middle Aged ; Regression Analysis ; Republic of Korea ; Spectrophotometry, Atomic

No abstract available.

BACKGROUND: Tracheal intubation causes a reflex tracheal constriction that leads to increased airway resistance. Inhalation anesthetics can prevent or minimize this response. Therefore, this study was conducted to evaluate the effect of 1 MAC sevoflurane or desflurane on respiratory mechanics in children after anesthetic induction using propofol and tracheal intubation. METHODS: Sixty children undergoing elective surgery with tracheal intubation were assigned into two groups at random, a 1 MAC concentration of sevoflurane (n = 30) and a desflurane (n = 30) group. Anesthesia was induced using propofol (1.5 mg/kg) and tracheal intubation was facilitated using rocuronium (0.6 mg/kg). A respiratory profile monitor was used to measure the respiratory resistance, dynamic compliance and peak inspiratory airway pressure. The measurements were made at three time points, after three inspirations from the beginning of mechanical ventilation (baseline) and at 5 and 10 min after the administration of inhalation anesthetics. RESULTS: Sevoflurane and desflurane led to a significant decrease in respiratory resistance and increased dynamic compliance at 5 and 10 min when compared to baseline. There were no significant differences in respiratory resistance and dynamic compliance between the two groups. CONCLUSIONS: A 1 MAC concentration of sevoflurane and desflurane has a similar bronchodilatory effect after tracheal intubation in children.
Airway Resistance ; Androstanols ; Anesthesia ; Anesthetics, Inhalation ; Child ; Compliance ; Constriction ; Humans ; Intubation ; Isoflurane ; Methyl Ethers ; Organothiophosphorus Compounds ; Propofol ; Reflex ; Respiration, Artificial ; Respiratory Mechanics

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) is not commonly used in the colorectal area because of technical difficulty and due to the characteristics of the organ. We therefore wanted to determine the efficacy and safety of endoscopic submucosal dissection in colorectal neoplasms. METHODS: Colorectal tumor lesions resected by ESD in a single medical center were analyzed retrospectively. RESULTS: A total of 47 patients were treated for 50 lesions. Mean age was 64.3+/-9.8 (43~85) years. Laterally spreading tumors were the most common type (44, 88%) followed by Is+IIa type tumors (6, 12%). The en bloc resection rate was 76% and the complete resection rate was 74%. The mean procedure time was 81.1+/-44.7 (20~180) minutes. The mean size of resected specimen was 26.9+/-10.4 (10~50) mm. The histological diagnosis determined that 24 lesions (48%) were tubular adenoma, 18 lesions (36%) were intramucosal cancer, 7 lesions (14%) were sm1 cancer and 1 lesion (2%) was over sm2 cancer. Bleeding occurred in 6 (12%) and perforations in 13 (26%) of the patients and all were treated successfully by endoscopic or conservative treatment. The concordance rate of pre and post ESD pathological diagnosis was only 47%. CONCLUSIONS: ESD is a feasible technique for treating superficial colorectal tumors with a high complete resection rate, minor invasiveness, and a high safety rate. In addition, ESD might be useful in establishing the complete pathological evaluation of colorectal epithelial neoplasm.
Adenoma ; Colorectal Neoplasms ; Hemorrhage ; Humans ; Neoplasms, Glandular and Epithelial ; Retrospective Studies