PURPOSE: To compare the improving effects of diabetic erectile dysfunction with two anti-glycemic agents; phlorizin and insulin. MATERIALS AND METHODS: Sixty Sprague-Dawley rats were divided into four groups (n=15 in each group): normal control (C), untreated diabetic rats (D), and diabetic rats treated by phlorizin (P) or insulin (I). Ten weeks after the diabetic induction using an injection of streptozotocin (55 mg/kg), four weeks of diabetic control was conducted. Erectile response, Western blot, and immunohistochemistry were assessed. RESULTS: During the experiment, the C-group showed continuous weight gain, while the other groups suffered from weight loss. After start of diabetic control, the body weight of I-group was increased; whereas, there was no meaningful change in the P-group. Meanwhile, comparable blood glucose levels were achieved in the P- and I-groups. The erectile response was markedly decreased in the D-group, whereas the P- and I-groups were similar as good as the C-group. In addition, D-group showed the significant decrease in the cavernosal smooth muscle content and increased apoptosis. Platelet endothelial cell adhesion molecule-1 protein expression, phosphorylation of endothelial nitric oxide synthase and myosin phosphatase target subunit 1 were significantly distorted in the D-group, while the P- and I-groups were comparable with the C-group. CONCLUSIONS: Phlorizin treatment resulted in the improvement of erectile function as same as insulin despite the lack of anabolic weight gains. These results suggest that control of blood glucose level rather than a type of anti-glycemic agents is more important for the prevention and treatment of diabetic erectile dysfunction
Animals ; Antigens, CD31 ; Apoptosis ; Blood Glucose ; Blotting, Western ; Body Weight ; Diabetes Complications ; Erectile Dysfunction ; Immunohistochemistry ; Insulin ; Male ; Muscle, Smooth ; Myosin-Light-Chain Phosphatase ; Nitric Oxide Synthase Type III ; Phlorhizin ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Streptozocin ; Weight Gain ; Weight Loss

PURPOSE: Gene therapy, stem cell therapy, and low-energy extracorporeal shockwave therapy (ESWT) have been investigated as treatments for refractory erectile dysfunction (ED), but inconclusive evidence has been obtained. We investigated the effect of a next-generation electromagnetic cylinder ESWT device on an animal model of ED. MATERIALS AND METHODS: Diabetes mellitus (DM)-induced rats were divided into 3 groups: group 1, control; group 2, DM; and group 3, DM+ESWT. Rats were treated with ESWT 3 times a week for 2 weeks. After the treatment course, intracavernous pressure was measured and the corpus cavernosum and cavernous nerve were evaluated. RESULTS: In the DM group, all parameters predicted to be significantly lower in the ED model had statistically significantly decreased (p < 0.01). As a measurement of erectile function, intracavernous pressure was evaluated. The DM+ESWT group exhibited significantly restored erectile function compared to the DM group (p < 0.05). Moreover, ESWT treatment restored smooth muscle content, as assessed by Masson's trichrome staining (p < 0.05). Finally, corporal tissue and the dorsal nerve were evaluated by immunohistochemistry, Western blotting, and ELISA. After ESWT treatment, vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), platelet endothelial cell adhesion molecule-1, cyclic guanosine monophosphate, and neuronal nitric oxide synthase (nNOS) expression levels were restored to levels in the DM group (p < 0.05). CONCLUSIONS: Electromagnetic cylinder ESWT device resulted in increased VEGF, nNOS, and eNOS expression; reduced smooth muscle atrophy; and increased endothelial cell regeneration in a DM-associated ED model. Our data suggest that safe and effective application could be possible in future clinical studies.
Animals* ; Antigens, CD31 ; Atrophy ; Blotting, Western ; Diabetes Mellitus ; Endothelial Cells ; Enzyme-Linked Immunosorbent Assay ; Erectile Dysfunction* ; Genetic Therapy ; Guanosine Monophosphate ; Immunohistochemistry ; Magnets ; Male ; Models, Animal* ; Muscle, Smooth ; Nitric Oxide Synthase Type I ; Nitric Oxide Synthase Type III ; Rats ; Regeneration ; Stem Cells ; Vascular Endothelial Growth Factor A

Hemangioma of the esophagus is a rare form of benign esophageal tumor. It usually presents as a single lesion located in the lower third of the esophagus and is mostly asymptomatic. However, it may occasionally cause hematemesis and/or obstruction. Surgical resection is the conventional treatment modality for managing esophageal hemangioma, but less invasive approaches such as endoscopic therapy are recently becoming more widely employed. Herein, we report a case of a 54-year-old man who presented with an esophageal hemangioma that was successfully treated by endoscopic mucosal resection without any complications.
Antigens, CD31/metabolism ; Esophageal Diseases/*diagnosis/surgery ; Esophagoscopy ; Esophagus/diagnostic imaging/metabolism/pathology ; Hemangioma/*diagnosis/surgery ; Humans ; Intestinal Mucosa/metabolism/pathology ; Male ; Middle Aged ; Tomography, X-Ray Computed

BACKGROUND: Although rarefaction of myocardial angiogenesis has been shown to be associated with left ventricular (LV) systolic dysfunction in animal models of ventricular hypertrophy, this relationship has not been investigated in depth nor validated in humans. We aimed to analyze the relationship of myocardial angiogenesis with various functional and structural ventricular remodeling parameters in moderate to severe aortic stenosis (AS) patients with normal LV ejection fraction (LVEF). METHODS: A total of 38 moderate or severe AS patients with LVEF > 50% were enrolled for the current study and all patients underwent LV endomyocardial biopsy at the septum during aortic valve replacement. The biopsy specimens were stained for platelet endothelial cell adhesion molecule-1 (CD31) to analyze the density of blood vessels in the myocardium. RESULTS: The degree of myocardial angiogenesis tended to increase with worse myocardial systolic function, LV filling pressure and progressed ventricular hypertrophy (Spearman's rho = -0.388, p = 0.016 for LVEF; Spearman's rho = 0.442, p = 0.007 for E/e'; Spearman's rho = 0.424, p = 0.008 for LV mass index). The degree of myocardial angiogenesis was also significantly associated with the degree of aortic valve stenosis (Spearman's rho = -0.368, p = 0.023). There was significant difference in the degree of myocardial angiogenesis according to the LV geometry (p = 0.016 for mean difference between different LV geometry groups by analysis of variance). Significant predictors of myocardial blood vessel density were LV mass index (beta = 0.398, p = 0.010) and LVEF (beta = -0.313, p = 0.028). CONCLUSION: There is a close relationship between myocardial angiogenesis and LV remodeling in moderate to severe AS patients with normal LVEF, with angiogenesis increasing with LV hypertrophy. Further studies to demonstrate the mechanism underlying this phenomenon is warranted.
Antigens, CD31 ; Aortic Valve ; Aortic Valve Stenosis* ; Biopsy ; Blood Vessels ; Echocardiography ; Humans ; Hypertrophy ; Models, Animal ; Myocardium ; Ventricular Remodeling*

BACKGROUND/OBJECTIVES: Abundant consumption of seaweeds in the diet is epidemiologically linked to the reduction in risk of developing cancer. In larger cases, however, identification of particular seaweeds that are accountable for these effects is still lacking, hindering the recognition of competent dietary-based chemo preventive approaches. The aim of this research was to establish the antiproliferative potency and angiosuppressive mode of action of Stoechospermum marginatum seaweed methanolic extract using various experimental models. MATERIALS/METHODS: Among the 15 seaweeds screened for antiproliferative activity against Ehrlich ascites tumor (EAT) cell line, Stoechospermum marginatum extract (SME) was found to be the most promising. Therefore, it was further investigated for its anti-proliferative activity in-vitro against choriocarcinoma (BeWo) and non-transformed Human embryonic kidney (HEK 293) cells, and for its anti-migratory/tube formation activity against HUVEC cells in-vitro. Subsequently, the angiosuppressive activity of S. marginatum was established by inhibition of angiogenesis in in-vivo (peritoneal angiogenesis and chorioallantoic membrane assay) and ex-vivo (rat cornea assay) models. RESULTS: Most brown seaweed extracts inhibited the proliferation of EAT cells, while green and red seaweed extracts were much less effective. According to the results, SME selectively inhibited proliferation of BeWo cells in-vitro in a dose-dependent manner, but had a lesser effect on HEK 293 cells. SME also suppressed the migration and tube formation of HUVEC cells in-vitro. In addition, SME was able to suppress VEGF-induced angiogenesis in the chorio allantoic membrane, rat cornea, and tumor induced angiogenesis in the peritoneum of EAT bearing mice. A decrease in the microvessel density count and CD31 antigen staining of treated mice peritoneum provided further evidence of its angiosuppressive activity. CONCLUSIONS: Altogether, the data underline that VEGF mediated angiogenesis is the target for the angiosuppressive action of SME and could potentially be useful in cancer prevention or treatment involving stimulated angiogenesis.
Allantois ; Animals ; Antigens, CD31 ; Carcinoma, Ehrlich Tumor ; Cell Line ; Chorioallantoic Membrane ; Choriocarcinoma ; Cornea ; Diet ; Female ; HEK293 Cells ; Human Umbilical Vein Endothelial Cells ; Humans ; Kidney ; Methanol ; Mice ; Microvessels ; Models, Theoretical* ; Peritoneum ; Pregnancy ; Rats ; Seaweed ; Vascular Endothelial Growth Factor A

BACKGROUND/OBJECTIVES: Abundant consumption of seaweeds in the diet is epidemiologically linked to the reduction in risk of developing cancer. In larger cases, however, identification of particular seaweeds that are accountable for these effects is still lacking, hindering the recognition of competent dietary-based chemo preventive approaches. The aim of this research was to establish the antiproliferative potency and angiosuppressive mode of action of Stoechospermum marginatum seaweed methanolic extract using various experimental models. MATERIALS/METHODS: Among the 15 seaweeds screened for antiproliferative activity against Ehrlich ascites tumor (EAT) cell line, Stoechospermum marginatum extract (SME) was found to be the most promising. Therefore, it was further investigated for its anti-proliferative activity in-vitro against choriocarcinoma (BeWo) and non-transformed Human embryonic kidney (HEK 293) cells, and for its anti-migratory/tube formation activity against HUVEC cells in-vitro. Subsequently, the angiosuppressive activity of S. marginatum was established by inhibition of angiogenesis in in-vivo (peritoneal angiogenesis and chorioallantoic membrane assay) and ex-vivo (rat cornea assay) models. RESULTS: Most brown seaweed extracts inhibited the proliferation of EAT cells, while green and red seaweed extracts were much less effective. According to the results, SME selectively inhibited proliferation of BeWo cells in-vitro in a dose-dependent manner, but had a lesser effect on HEK 293 cells. SME also suppressed the migration and tube formation of HUVEC cells in-vitro. In addition, SME was able to suppress VEGF-induced angiogenesis in the chorio allantoic membrane, rat cornea, and tumor induced angiogenesis in the peritoneum of EAT bearing mice. A decrease in the microvessel density count and CD31 antigen staining of treated mice peritoneum provided further evidence of its angiosuppressive activity. CONCLUSIONS: Altogether, the data underline that VEGF mediated angiogenesis is the target for the angiosuppressive action of SME and could potentially be useful in cancer prevention or treatment involving stimulated angiogenesis.
Allantois ; Animals ; Antigens, CD31 ; Carcinoma, Ehrlich Tumor ; Cell Line ; Chorioallantoic Membrane ; Choriocarcinoma ; Cornea ; Diet ; Female ; HEK293 Cells ; Human Umbilical Vein Endothelial Cells ; Humans ; Kidney ; Methanol ; Mice ; Microvessels ; Models, Theoretical* ; Peritoneum ; Pregnancy ; Rats ; Seaweed ; Vascular Endothelial Growth Factor A

Splenic hamartoma is a very rare benign tumor, which is usually found incidentally after splenectomy or autopsy. Although percutaneous needle biopsy can be performed, it carries a high risk of bleeding after the procedure. Therefore, diagnosis is usually made by surgical resection. Herein, we report a case of splenic hamartoma diagnosed by magnetic resonance imaging and contrast-enhanced ultrasonography, which enables visualization of the unique signals of microbubbles in the vessels in real time. Relevant literature is also reviewed.
Adult ; Antigens, CD31/metabolism ; Antigens, CD34/metabolism ; Contrast Media ; Female ; Hamartoma/*diagnosis/pathology/ultrasonography ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging ; Splenic Diseases/*diagnosis/pathology/ultrasonography ; Tomography, X-Ray Computed

Cartilage oligomeric matrix protein-angiopoietin-1 (COMP-Ang1) is an angiogenic factor for vascular angiogenesis. The aim was to investigate the effect of an intracavernosal injection of COMP-Ang1 on cavernosal angiogenesis in a diabetic rat model. Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats made up the experimental group (1 yr old) and Long-Evans Tokushima Otsuka (LETO) rats made up the control group. The experimental group was divided into vehicle only, 10 microg COMP-Ang1, and 20 microg COMP-Ang1. COMP-Ang1 was injected into the corpus cavernosum of the penis. After 4 weeks, the penile tissues of the rats were obtained for immunohistochemistry and Western blot analysis. The immunoreactivity of PECAM-1 and VEGF was increased in the COMP-Ang1 group compared with the vehicle only group. Moreover, the expression of PECAM-1 and VEGF was notably augmented in the 20 microg Comp Ang-1 group. In the immunoblotting study, the expression of PECAM-1 and VEGF protein was significantly less in the OLEFT rats than in the control LETO rats. However, this expression was restored to control level after intracavernosal injection of COMP-Ang1. These results show that an intracavernosal injection of COMP-Ang1 enhances cavernous angiogenesis by structurally reinforcing the cavernosal endothelium.
Angiopoietin-1/genetics/*metabolism ; Animals ; Antigens, CD31/metabolism ; Blood Glucose/analysis ; Blotting, Western ; Body Weight ; Cartilage Oligomeric Matrix Protein/genetics/*metabolism ; Diabetes Mellitus, Experimental/*pathology ; Immunohistochemistry ; Male ; Neovascularization, Physiologic/*drug effects ; Penis/metabolism/pathology ; Rats ; Rats, Long-Evans ; Recombinant Fusion Proteins/biosynthesis/genetics/*pharmacology ; Vascular Endothelial Growth Factor A/metabolism

Previous studies reported that oxaliplatin is associated with sinusoidal obstruction syndrome. However few reports on oxaliplatin induced liver fibrosis are found in the literature. Furthermore pathogenesis of liver fibrosis is not well known. We report a case of 45-yr-old Korean man in whom liver fibrosis with splenomegaly developed after 12 cycles of oxaliplatin based adjuvant chemotherapy for colon cancer (T4N2M0). Thorough history taking and serological examination revealed no evidence of chronic liver disease. Restaging CT scans demonstrated a good response to chemotherapy. Five month after chemotherapy, he underwent right hepatectomy due to isolated metastatic lesion. The liver parenchyma showed diffuse sinusoidal dilatation and centrilobular vein fibrosis with necrosis without steatosis. We could conclude that splenomegaly was due to perisinusoidal liver fibrosis and liver cell necrosis induced portal hypertension by oxaliplatin. In addition, to investigate the pathogenesis of liver fibrosis, immunohistochemical stains such as CD31 and alpha-smooth muscle actin (alpha-SMA) were conducted with control group. The immunohistochemical stains for CD31 and alpha-SMA were positive along the sinusoidal space in the patient, while negative in the control group. Chemotherapy with oxaliplatin induces liver fibrosis which should be kept in mind as a serious complication.
Actins/metabolism ; Antigens, CD31/metabolism ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Camptothecin/*analogs & derivatives/therapeutic use ; Chemotherapy, Adjuvant ; Colonic Neoplasms/*drug therapy ; Fluorouracil/therapeutic use ; Humans ; Hypertension, Portal/etiology ; Immunohistochemistry ; Leucovorin/therapeutic use ; Liver Cirrhosis/*diagnosis/etiology/pathology ; Liver Neoplasms/secondary/surgery ; Male ; Middle Aged ; Organoplatinum Compounds/*administration & dosage/adverse effects/therapeutic use ; Splenomegaly/*diagnosis/etiology ; Thrombocytopenia/etiology ; Tomography, X-Ray Computed

BACKGROUND: Partial or complete necrosis of a skin flap is a common problem. Polydeoxyribonucleotide (PDRN) can be extracted from trout sperm and used as a tissue repair agent. The aim of this study was to investigate whether PDRN could improve the survival of random pattern skin flaps in rats. METHODS: Twenty-two male Sprague-Dawley rats were randomly divided into two groups: the PDRN treatment group (n=11) and the control group (n=11). Caudally pedicled random pattern skin flaps were elevated on their dorsal skin and resutured. The treatment group received daily intraperitoneal administration of PDRN (8 mg/kg/day), and the control group received fluid vehicle (NaCl 0.9%, 8 mg/kg/day) from day 0 to day 6. On day 7, the flap survival was evaluated and the harvested tissue surrounding the demarcation line of the necrotic area was stained with H&E, anti-rat vascular endothelial cell growth factor (VEGF) antibody, and PECAM-1/CD31 antibody. RESULTS: The average necrotic area of the flap in the PDRN group was significantly smaller when compared with that of the control group. Histologic and immunohistochemical evaluation showed that granulation thickness score and VEGF-positive staining cells were marked higher in the PDRN group than in the control group. PECAM-1/CD31-positive microvascular densities were significantly higher in the PDRN group when compared with the control group. CONCLUSIONS: This study confirms that PDRN improves the survival of random pattern skin flaps in rats. These results may represent a new therapeutic approach to enhancing flap viability and achieving faster wound repair.
Angiogenesis Modulating Agents ; Animals ; Antigens, CD31 ; Endothelial Cells ; Humans ; Male ; Necrosis ; Polydeoxyribonucleotides ; Rats ; Rats, Sprague-Dawley ; Skin ; Spermatozoa ; Surgical Flaps ; Trout ; Vascular Endothelial Growth Factors