The Notch pathway is a critical regulator of angiogenesis in a skin model of ischemia

WOS: 000355334000001PubMed ID: 25834117The Notch pathway is definitely required for normal vascular development. Although the contribution of Notch in postnatal angiogenesis is the focus of intense investigation, the implication of Notch in reparative neovascularization in the skin remains unexplored. In this study, we investigated Notch changes using a skin model of ischemia. Thirty Sprague-Dawley rats were divided into two groups. In the surgery group (n = 24), a caudally based dorsal skin flap was raised and sutured back into its initial position. In the control group, no surgical procedure was performed. Tissue biopsies were obtained at different time intervals. Tissue specimens were assessed for Delta-like ligand 4 (DLL4) and vascular endothelial growth factor (VEGF) gene expression by real-time polymerase chain reaction (PCR). Immunohistochemical staining was used for detection of DLL4 in tissue materials. Quantitative assessment of skin flap microvasculature was made. Compared with normoperfused tissue, VEGF and DLL4 expressions increased significantly (p < 0.01). Immunohistochemical analysis revealed weak and patchy expression of DLL4 in microvascular endothelial cells of normoperfused tissues. Conversely, DLL4 expression was upregulated in capillary endothelial cells after ischemia. In conclusion, in this study we have shown that the Notch ligand DLL4 is upregulated in skin tissue after ischemia. A deeper understanding of these fundamental principles will aid in the development of new avenues for the treatment of blood vessel-related skin pathologies.Baskent University Research FundBaskent UniversityThis study was approved by Baskent University Ethical Committee for Experimental Research on Animals and supported by Baskent University Research Fund

Corneal Collagen Cross-Linking in Pellucid Marginal Degeneration: 2 Patients, 4 Eyes

Purpose. To report the long-term results of corneal collagen cross-linking (CXL) with riboflavin and ultraviolet-A irradiation in 4 eyes of 2 patients affected by pellucid marginal degeneration (PMD). Methods. This study involved the retrospective analysis of 4 eyes of 2 patients with PMD that underwent CXL treatment. Of the eyes, three had only CXL treatment and one had CXL treatment after an intrastromal corneal ring segment implantation. We have pre- and postoperatively evaluated uncorrected distance visual acuity (UDVA), best corrected distance visual acuity (BCDVA), corneal topography (Pentacam), specular microscopy, and pachymetry. Results. Patient 1 was a woman, aged 35, and Patient 2 was a man, aged 33. The right eye of Patient 1 showed an improvement in her BCDVA, from 16/40 to 18/20 in 15 months, and her left eye improved from 12/20 to 18/20 in 20 months. Patient 2’s right eye showed an improvement in his BCDVA, from 18/20 to 20/20 in 43 months, and his left eye improved from 16/20 to 18/20 in 22 months. No complications were recorded during or after the treatment. Conclusion. CXL is a safe tool for the management of PMD, and it can help to stop the progression of this disease

Corneal Collagen Cross-Linking in Pellucid Marginal Degeneration: 2 Patients, 4 Eyes

Purpose. To report the long-term results of corneal collagen cross-linking (CXL) with riboflavin and ultraviolet-A irradiation in 4 eyes of 2 patients affected by pellucidmarginal degeneration (PMD). Methods. This study involved the retrospective analysis of 4 eyes of 2 patients with PMDthat underwent CXL treatment. Of the eyes, three had only CXL treatment and one had CXL treatment after an intrastromal corneal ring segment implantation. We have pre-and postoperatively evaluated uncorrected distance visual acuity (UDVA), best corrected distance visual acuity (BCDVA), corneal topography (Pentacam), specular microscopy, and pachymetry. Results. Patient 1 was a woman, aged 35, and Patient 2 was a man, aged 33. The right eye of Patient 1 showed an improvement in her BCDVA, from16/40 to 18/20 in 15months, and her left eye improved from 12/20 to 18/20 in 20months. Patient 2's right eye showed an improvement in his BCDVA, from 18/20 to 20/20 in 43 months, and his left eye improved from 16/20 to 18/20 in 22 months. No complications were recorded during or after the treatment. Conclusion. CXL is a safe tool for the management of PMD, and it can help to stop the progression of this disease

Use of soluble complement receptor type 1 to prevent local and distant organ injury in a rat intestinal ischemia reperfusion model

Introduction: In this experimental study we aimed to examine the in vivo effect of soluble complement receptor type 1 (sCR1) in preventing local and distant organ injury in an ischemia reperfusion model via the superior mesenteric artery (SMA). Using these data, it may be possible to determine the clinical usage of sCR1. Material and Methods: 24 male rats, weighing between 200 and 250 g, were classified into four groups. In group 1, the SMA was clamped for 60 minutes. In group 2, intravenous (IV) sCR1 was given after laparotomy. In group 3, the SMA was clamped for 60 min, at the 60th minute IV sCR1 was administered, and then 1 min later reperfusion was carried out. Group 4 was the laparotomy group. To investigate organ injury, liver function tests (serum AST and ALT levels) and kidney function tests (serum BUN and creatinine levels) were carried out. To evaluate the systemic and local effects of inflammation, total serum levels of protein, albumin, tumour necrosis factor-alpha (TNF-&alpha;), and interleukin-6 (IL-6) were tested. In tissue samples, glutathione (GSH), malondialdehyde (MDA), and myeloperoxidase (MPO) positive neutrophil counts were identified. Results: According to the statistical analysis, sCR1 was shown to reduce the ischemia-reperfusion injury and have antiinflammatory effects. In addition, distant organ injury due to reperfusion was prevented by sCR1. Conclusion: sCR1 was verified to decrease both mortality and morbidity. [Arch Clin Exp Surg 2017; 6(3.000): 126-131

A Rat Model of Acute Respiratory Distress Silymarin's Antiinflamatory and Antioxidant Effect

Objective: In this study, it was aimed to evaluate the anti-inflammatory and antioxidative effects of Silymarin in rats in whom artificial acute pulmonary damage was provided with caecal ligation-perforation method. Material and Method: Forty-six rats were randomized to sham (n=14), control (n=16), silymarin (n=16) groups. Each group had early and late subgroups. Silimarin was administered in the silimarin group and saline was administerd in control and sham groups. Artificial acute pulmonary damage associated with sepsis was provided with caecal ligation-perforation method in control and silimarin groups. Rats in the early subgroup Were terminated at the end of the 12th hour and threats in the late group were followed-up. Serum and bronchoalveolar lavage fluid (BAL) tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6; lung tissue malondialdehyde (MDA) and glutathione (GSH) levels; lung histopathologic examination; and lung wet-to-dry (w/d) weight ratio measurements were used to compare and evaluate the severity of lung injury between the groups. Results: Mortality rates for silymarin and control groups were 62.5% and 12.5%, respectively (log-rank p=0.0506). Compared with the silymarin group, the control group exhibited significantly more severe lung injury, as indicated by higher mean values for serum and BAL TNF-alpha, IL-1beta and IL-6 (p<0.05 for all measurements), total lung histopathologic injury score (p=0.001), w/d (p=0.019) and lung-tissue MDA (p=0.011) levels. Lung tissue GSH levels were significantly higher in silymarin group than control group (p=0.001). Conclusion: Silymarin reduces the severity of sepsis induced-acute lung injury and may also improve survival in a cecal ligation and perforation rat model. These beneficial effects of this agent are probably due to its inhibitory effects on inflammatory process and oxidative injury

The prevalence and systemic risk factors of diabetic macular edema: a cross-sectional study from Turkey

Abstract Background The aim of this study was to evaluate the prevalence of diabetic macular edema (DME) utilizing optical coherence tomography (OCT), and to clarify the effects of the systemic findings and risk factors on the development of DME. Methods This cross-sectional study was conducted in the departments of ophthalmology and endocrinology at the Dokuz Eylul University School of Medicine in Izmir, Turkey. The demographics, type and duration of diabetes mellitus, treatment modality, smoking and alcohol consumption habits, as well as the systemic blood pressure, renal functional tests, hemoglobulin A1c level, serum lipid profile, and 24-h urine albumin level were noted and statistically analyzed. The relationships between the systemic findings and DME were studied. Results Four-hundred and thirteen eyes of 413 diabetic patients who were examined between January 2011 and July 2012 were enrolled in this study. The prevalence of DME was 15.3% among the patients. The males exhibited DME significantly more frequently than the females (p = 0.031), and the duration of diabetes was significantly longer in those patients with DME (p < 0.001). Those patients without DME frequently used antihyperlipidemic drugs and had a higher level of high density lipoprotein cholesterol (p = 0.040 and p = 0.046, respectively). The patient’s alcohol consumption, nephropathy, neuropathy, previous cataract surgery, severity of diabetic retinopathy, and insulin usage were statistically significant factors with regard to the DME prevalence. Conclusions This study demonstrated the prevalence of DME in Turkey by utilizing OCT. The development of DME can be avoided or limited and the response to treatment may be improved by the regulation of the DME risk factors

Amifostine enhances the antioxidant and hepatoprotective effects of UW and HTK preservation solutions

AIM: To investigate whether amifostine contributes to the antioxidant and cytoprotective effects of histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions. METHODS: Forty-eight Sprague Dawley male rats were equally divided into six groups: (1) ringer Lactate (RL) group; (2) RL + amifostine (RL + A) group; (3) HTK group; (4) HTK + A group; (5) UW group; and (6) UW + A group. Rats in the RL + A, HTK + A and UW + A groups were administered amifostine intraperitoneally at a dose of 200 mg/kg prior to laparotomy. The RL group was perfused with RL into the portal vein. The RL + A group were perfused with RL into the portal vein after amifostine administration. The HTK group received an HTK perfusion while the HTK + A group received an HTK perfusion after administration of amifostine. The UW group received a perfusion of UW, while the UW + A group received a UW perfusion after amifostine administration. Liver biopsy was performed to investigate histopathological, immunochemical [transferase mediated dUTP nick end labeling (TUNEL), inducible nitric oxide syntetase (iNOS)] and ultrastructural alterations. Biochemical alterations were determined by examining levels of alanine aminotransferase, alkaline phosphatase and nitric oxide in the perfusion fluid. RESULTS: Pathological sinusoidal dilatation and centrilobular hydropic alteration were significantly lower in the groups that received amifostine prior to preservation solution perfusion. Although the best results were obtained in the UW + A group, we did not observe a statistically significant difference between the UW + A and HTK + A groups. iNOS grades were significantly lower in the amifostine groups 12 h after treatment. When the amifostine groups were compared against each other, the iNOS grades obtained from the UW + A and HTK + A groups were similar while the RL + A group had a much poorer score. TUNEL assays demonstrated a lower apoptosis ratio in the amifostine groups than in the non-amifostine groups 12 h after treatment. No statistically significant difference was observed between the UW + A and HTK + A groups for apoptosis. Cellular ultrastructure was best preserved in the UW + A and HTK + A groups. CONCLUSION: Here, we show that preoperative administration of a single dose of amifostine is sufficient to minimize the preservation damage in hepatic cells. (C) 2014 Baishideng Publishing Group Inc. All rights reserved

Evaluation of vascular endothelial growth factor A and endostatin levels in induced sputum and relationship to bronchial hyperreactivity in patients with seasonal allergic rhinitis

Background: Studies about the pathogenesis of bronchial hyperreactivity (BHR) in patients with allergic rhinitis (AR) and its relationship with lower airway remodeling are extremely limited. In this study, bronchial vascular remodeling and its relationship with BHR were evaluated by measurement of vascular endothelial growth factor A (VEGF-A) and endostatin in patients with seasonal AR (SAR)