Comparison of Intraocular Cytokine Levels of Choroidal Neovascularization Secondary to Different Retinopathies

Purpose: To investigate and compare the aqueous concentrations of vascular endothelial growth factor (VEGF) and other inflammatory cytokines in various choroidal neovascularization (CNV) diseases and types.Methods: This observational study included 127 naive eyes with CNV and 43 control eyes with cataracts. Aqueous humor (AH) samples were obtained prior to intravitreal anti-VEGF injection or cataract surgery. Multiple inflammatory cytokines, including VEGF, interleukin (IL) 6, IL-8, IL-10, interferon-inducible protein 10 (IP-10), and monocyte chemotactic protein 1 (MCP-1) levels, were measured using a multiplex bead assay. The angiogenesis index was defined as the ratio of IP-10 to MCP-1. In addition, the relationship among AH cytokine levels, central macular thickness (CMT), and CNV size on optical coherence tomography angiography (OCTA) was evaluated.Results: Except in the myopic CNV group (P = 0.452), the AH concentration of VEGF was significantly higher in all other CNV groups than in the control group (P < 0.05 for all comparisons). IL-8, IL-10, IP-10, and MCP-1 levels (P < 0.05 for all groups) were significantly higher in all CNV diseases except those with neovascular central serous chorioretinopathy. The angiogenesis index was significantly higher in all CNV diseases (P < 0.05 for all comparisons). The VEGF level may be associated with the size of the CNV on OCTA (p = 0.043).Conclusions: The level of intraocular inflammatory cytokines varied among different CNV diseases and CNV types. Therefore, the angiogenesis index may be a more sensitive indicator of angiogenesis.

CHANGES IN VASCULAR ENDOTHELIAL GROWTH FACTOR LEVEL IN HELICOBACTER PYLORI-ASSOCIATED GASTRODUODENAL DISEASES

A populational infection with Helicobacter (H.) pylori poses a global problem. Mucosal colonization of H. pylori in the gastroduodenal area can initiate development multiple diseases with hyper-or hypoplasia of mucosal epithelial cells secreting vascular endothelial growth factor (VEGF). The aim of the study was to assess VEGF serum level, its diagnostic and prognostic value in diseases affecting the gastroduodenal area. Material and methods. 180 patients with exacerbated chronic gastritis, gastric ulcer, duodenal ulcer as well as 30 healthy volunteers were examined after providing an informed consent. Patients were divided into groups depending on the degree of mucous contamination with H. pylori. In the subjects examined during esophagogastroduodenoscopy, a biological material was collected during targeted biopsy for microscopic and histological studies. Blood samples for immunological examination were obtained in the morning on an empty stomach from the ulnar vein in the volume of 5 ml, and the serum was isolated by centrifugation. The level of VEGF, pepsinogens, and titer of total antibodies against the H. pylori cytotoxin-associated protein were determined in the blood serum from the subjects by using the enzyme immunoassay method. The long-term prognosis was analyzed for up to 2 years. The data obtained were processed statistically. Results. Patients were found to have excessive serum VEGF levels in healthy volunteers. For gastric ulcer associated with H. pylori, 80% of cases had increased discriminatory VEGF level. In patients, direct relationships between the serum VEGF level and degree, stage of gastritis, the degree of contamination with H. pylori, the serum pepsinogens level were uncovered. Regression analysis found that patients with diseases targeting gastroduodenal area had serum VEGF level equal to or greater than 231 pg/ml in 60% of cases that correctly predicted an increase in mucosal atrophy. If the amount of VEGF ≥373 pg/ml in 91.5% of cases, then ulceration of gastric epithelium developed, whereas for ≥396 pg/ml level it was observed in 89% cases with ulceration of the intestinal epithelium. The probability of gastroduodenal bleeding at a serum VEGF level of 408 pg/ml or higher was predicted correctly in 96% of cases. Conclusion. More than 54% of patients with H. pylori-associated chronic gastritis, peptic ulcer disease had level of VEGF significantly exceeding magnitude found in healthy volunteers and the discriminatory level reflects the morphofunctional state of the stomach and duodenum. Assessing serum VEGF level in gastroduodenal diseases can be recommended for predicting development of atrophy, ulceration of the gastric and intestinal epithelium, and gastroduodenal bleeding.

Prognostic significance of VEGF signaling system components and matrix metalloproteinases in blood serum of gastric cancer patients

Analysis of long-term treatment results of 77 primary gastric cancer patients at stage I-IV of the tumor process followed during 1 - 41 months (median - 6.4 months) from the onset of specific treatment are presented depending on the basal levels of VEGF, soluble forms of its receptors (sVEGFR1, sVEGFR2) and matrix metalloproteinases (MMP-2, 7, 9) in blood serum. Overall survival assessed by Kaplan-Meyer analysis and with the help of Cox multiparametric regression model was applied as the criterion of prognostic value. It was found that at high (≥ 420 pg/ml) serum VEGF, the overall survival of patients with gastric cancer was statistically significantly lower than at the marker’s levels below 420 pg/ml (p<0.011): 3-year’s survival comprised 46,3±12,5% and 88,2±7,8% respectively. Median survival of patients with high VEGF level comprised 21.7 months, of those with low VEGF was not achieved during the whole follow-up period. Serum sVEGFR1, sVEGFR2, MMP-2, 7 and 9 levels were not significantly associated with the overall survival of patients included in this study. Only index M of TNM system and serum VEGF level demonstrated an independent prognostic value in multiparametric model (p=0.036). Thus, it was confirmed that VEGF signaling pathway plays an important role in gastric cancer, and its components - in the first place, VEGF A - are substantial factors of disease prognosis, and can also be useful for monitoring of treatment efficiency.

Acute Mountain Sickness Following Incremental Trekking to High Altitude: Correlation With Plasma Vascular Endothelial Growth Factor Levels and the Possible Effects of Dexamethasone and Acclimatization Following Re-exposure

Purpose: The recognition and treatment of high-altitude illness (HAI) is increasingly important in global emergency medicine. High altitude related hypobaric hypoxia can lead to acute mountain sickness (AMS), which may relate to increased expression of vascular endothelial growth factor (VEGF), and subsequent blood-brain barrier (BBB) compromise. This study aimed to establish the relationship between AMS and changes in plasma VEGF levels during a high-altitude ascent. VEGF level changes with dexamethasone, a commonly used AMS medication, may provide additional insight into AMS.Methods: Twelve healthy volunteers ascended Mt Fuji (3,700 m) and blood samples were obtained at distinct altitudes for VEGF analysis. Oxygen saturation (SPO2) measurements were also documented at the same time-point. Six out of the 12 study participants were prescribed dexamethasone for a second ascent performed 48 h later, and blood was again collected to establish VEGF levels.Results: Four key VEGF observations could be made based on the data collected: (i) the baseline VEGF levels between the two ascents trended upwards; (ii) those deemed to have AMS in the first ascent had increased VEGF levels (23.8–30.3 pg/ml), which decreased otherwise (23.8–30.3 pg/ml); (iii) first ascent AMS participants had higher VEGF level variability for the second ascent, and similar to those not treated with dexamethasone; and (iv) for the second ascent dexamethasone participants had similar VEGF levels to non-AMS first ascent participants, and the variability was lower than for first ascent AMS and non-dexamethasone participants. SPO2 changes were unremarkable, other than reducing by around 5% irrespective of whether measurement was taken for the first or second ascent.Conclusion: First ascent findings suggest a hallmark of AMS could be elevated VEGF levels. The lack of an exercise-induced VEGF level change strengthened the notion that elevated plasma VEGF was brain-derived, and related to AMS.

Efek Terapi Adjuvan Extracorporal Shockwave terhadap Penyembuhan Ulkus Kaki Diabetik Penyandang Diabetes Melitus Tipe 2 dengan Penanda Vascular Endothelial Growth Factor

Diabetic foot ulcer (DFU) prevalence tends to increase every year. Within 30 seconds it is predicted that one leg will be amputated due to DFU. New blood formation triggered by adjuvant extracorporeal shock wave therapy (ESWT) on increasing VEGF level is expected to promote DFU healing. This study was aimed to prove whether ESWT as an adjuvant therapy could stimulate DFU healing by increasing VEGF serum level. This was a quasi-experimental study using two groups, the ESWT and the control groups. Two repeated measurements of VEGF levels and PEDIS scores were performed. The ESWT group (17 patients) received the adjuvant ESWT and the control group (7 patients) received conventional wound care therapy. Both groups received 8-time treatment for 4 weeks. Measurements of VEGF levels and PEDIS scores were performed at baseline and after 4 weeks. The results showed that the PEDIS score of the ESWT group decreased, albeit, not in the control group. The VEGF level of the ESWT group significantly increased (mean rank=13.24) compared to the control group (mean rank=7.33). The Wilcoxon signed-ranks test indicated that the PEDIS score in ESWT group had a significant decrease compared to the control group (mean rank=7.50), Z=-3.372, p=<.001. The Pearson correlation test showed a significant relationship between VEGF value and the PEDIS score reduction (81.4%). In conclusion, the adjuvant ESWT therapy could promote DFU healing (reduced PEDIS score) and increase VEGF levels in DFU patients.Keywords: ESWT; VEGF; diabetic foot ulcer (DFU) Abstrak: Prevalensi ulkus kaki dibetik (UKD) terus meningkat setiap tahunnya dan dalam 30 detik diprediksi terdapat satu kaki yang diamputasi karena UKD. Pembentukan pembuluh darah baru yang dipicu oleh penggunaan adjuvan ESWT terhadap peningkatan kadar VEGF diharapkan dapat memper-cepat penyembuhan UKD. Penelitian ini bertujuan untuk membuktikan terapi adjuvan ESWT dapat meningkatkan kadar VEGF dalam penyembuhan UKD. Jenis penelitan ialah kuasi-eksperimental yang membandingkan dua kelompok perlakuan (ESWT vs kontrol) melalui dua pengukuran berulang terhadap kadar VEGF dan skor pedis. Kelompok ESWT (17 pasien) mendapatkan terapi adjuvan ESWT dan kelompok kontrol (7 pasien) mendapatkan terapi konvensional perawatan luka. Kedua kelompok mendapatkan perlakuan 2 kali per minggu selama 4 minggu. Pengukuran kadar VEGF dan skor pedis pada baseline dan setelah selesai 4 minggu perlakuan. Hasil penelitian mendapatkan penurunan skor PEDIS hanya pada kelompok ESWT (14 pasien), Kadar VEGF kelompok perlakuan didapatkan meningkat bermakna (mean rank=13,24) dibandingkan kelompok kontrol (mean rank=7,33) (p<0,001). Wilcoxon Signed-Ranks Test mengindikasikan bahwa nilai skor PEDIS kelompok ESWT mengalami penurunan bermakna dibandingkan kelompok kontrol (mean rank=7,0), Z=-3,372, p=<0,001. Uji korelasi Pearson menunjukkan hubungan bermakna antara perubahan nilai VEGF dengan skor pedis (81,4%). Simpulan penelitian ini ialah terapi adjuvan ESWT dapat memicu penyembuhan UKD (menurunkan skor PEDIS) dan meningkatkan kadar VEGF pada pasien UKDKata kunci: ESWT; VEGF; ulkus kaki diabetik (UKD)

Diagnostic Value of Video-Dermatoscopy in Patients with Systemic Sclerosis and Dermatomyositis with its relation to Serum Vascular Endothelial Growth Factor (S.VEGF)

Background Systemic sclerosis and dermatomyositis are autoimmune connective tissue diseases affecting the skin and various internal organs. Systemic sclerosis is characterized by fibrotic arteriosclerosis of peripheral and visceral vasculature. Objective Analysis of video dermatoscopic picture of systemic sclerosis and dermatomyositis patients and find a characteristic feature for both. Assess serum vascular endothelial growth factor (VEGF) in these patients using enzyme linked immunosorbent assay (ELISA) kits. Perform a statistical analysis of the results to find a relation between video dermatoscopic Picture of systemic sclerosis and dermatomyositis patients and their serum VEGF to help in diagnosis, grading, prognosis and management. Patients and Methods Our case control study included 25 patients with SSc or DM (2555 years) recruited from Ain Shams University Hospitals and 25 apparent healthy controls with matched age and sex. After the study had been approved by Ain shams University of Medical Sciences Research Ethics Committee, all the subjects signed an informed consent before inclusion in the study. Results Serum VEGF level was highly significant in patients than in controls. This may be explained by the excessive release of VEGF in patients due to hypoxia caused by microvascular occlusion that not present in healthy controls. Conclusion Microvascular abnormalities are the earliest features of SSc and DM with elevation of serum VEGF level indicating its role in disease pathogenesis and disturbance of microvessls. Videodermoscopy and measurement of serum VEGF are effective tools in diagnosis, prognosis and grading of autoimmune connective tissue diseases as SSc and DM.

Dl-3-n-Butylphthalide Ameliorates Diabetic Nephropathy by Ameliorating Excessive Fibrosis and Podocyte Apoptosis

Diabetic nephropathy (DN) is a common diabetes associated complication. Thus, it is important to understand the pathological mechanism of DN and find the appropriate therapeutic strategy for it. Dl-3-n-Butylphthalide (DL-NBP) has anti-inflammatory and antioxidant effects, and been widely used for the treatment of stroke and cardiovascular diseases. In this study, we selected three different doses (20, 60, and 120 mg⋅kg−1 d−1) of DL-NBP and attempted to elucidate its role and molecular mechanism underlying DN. We found that DL-NBP, especially at the dose of 60 or 120 mg⋅kg−1 d−1, could significantly ameliorate diabetes-induced elevated blood urea nitrogen (BUN) and creatinine level, and alleviate renal fibrosis. Additionally, the elevated expressions of collagen and α-smooth muscle actin (α-SMA) in the kidney from db/db mice were found to be significantly suppressed after DL-NBP treatment. Furthermore, mechanistic studies revealed that DL-NBP inhibits pro-inflammatory cytokine levels, thereby ameliorating the development of renal fibrosis. Moreover, we found that DL-NBP could not only reduce the endoplasmic reticulum stress (ERS), but also suppress activation of the renin-angiotensin system to inhibit vascular endothelial growth factor (VEGF) level, which subsequently reduces the podocyte apoptosis in kidney of db/db mice. In a word, our findings suggest that DL-NBP may be a potential therapeutic drug in the treatment of DN.

Effect of early exogenous supplementation of rhIGF-1 on oxygen-induced retinopathy in a mice model of prematurity, and on expressions of IGF-1 and VEGF

Purpose: To investigate the effect of early exogenous supplementation of recombinant human insulinlike growth factor (rhIGF-1) on oxygen-induced mouse model of retinopathy of prematurity (ROP). Methods: Three groups of healthy SPF grade C57BL/6 mice were used in this study, with 20 mice in each group. Hyperoxia saline (HS) and hyperoxia rhIGF-1 (HrGF) groups were placed in a closed oxygen chamber for one week and returned to the normal environment on the 15th day. The hyperoxia rhIGF-1 (HrGF) group was intraperitoneally injected with rhIGF-1 (1.5 mg/kg), while mice in high-oxygen saline (HS) group received normal saline. The air group (AG) was untreated. Changes in retinal blood vessel distributions, expression levels of serum IGF-1 and VEGF, and retinal IGF-1 and VEGF were determined. Results: On day 20, pronounced neo-vascularization was observed, but the distribution was disordered. Serum IGF-1 levels in AG and HrGF were significantly higher than that in HS group, but VEGF level was lower in HS mice (p < 0.05). VEGF level in hyperoxia rhIGF-1 group on days 11 and 15 decreased, relative to control value, while retinal IGF-1 and VEGF in AG and hyperoxia rhIGF-1 mice were elevated, relative to corresponding values in HS mice (p < 0.05). Conclusion: Early exogenous supplementation of rhIGF-1 exerts a therapeutic effect on ROP. Thus, rhIGF-1 may be a potential drug regimen for ROP in clinics.