DESIGN: A questionnaire containing 47 questions was developed which encompassed clinical scenarios such as treatment response to anti-vascular endothelial growth factor and steroid, treatment side effects, as well as cost and compliance/reimbursement in the management of DME using a Dephi questionnaire as guide.
METHODS: An expert panel of 12 retinal specialists from Singapore, Malaysia, Philippines, India and Vietnam responded to this questionnaire on two separate occasions. The first round responses were compiled, analyzed and discussed in a round table discussion where a consensus was sought through voting. Consensus was considered achieved, when 9 of the 12 panellists (75%) agreed on a recommendation.
RESULTS: The DME patients were initially profiled based on their response to treatment, and the terms target response, adequate response, nonresponse, and inadequate response were defined. The panellists arrived at a consensus on various aspects of DME treatment such as need for classification of patients before treatment, first-line treatment options, appropriate time to switch between treatment modalities, and steroid-related side effects based on which recommendations were derived, and a treatment algorithm was developed.
CONCLUSIONS: This consensus article provides comprehensive, evidence-based treatment guidelines in the management of DME in Asian population. In addition, it also provides recommendations on other aspects of DME management such as steroid treatment for stable glaucoma patients, management of intraocular pressure rise, and recommendations for cataract development.
MATERIALS AND METHODS: Adipose stromal cells were cultured in three different types of medium: (i) F12/DMEM (FD) supplemented with 10% FBS from passage 0 (P0) to P6; (ii) FD supplemented with 2% FBS at P6; and (iii) FD supplemented with 2% FBS plus 50 ng/ml of VEGF at P6. Morphological changes and growth rate of ASCs were recorded. Changes in stemness, angiogenic and endogenic genes' expressions were analysed using Real-Time PCR.
RESULTS: Adipose stromal cells changed from fibroblast-like shape when cultured in 10% FBS medium to polygonal when cultured in 2% FBS plus VEGF-supplemented medium. Their growth rate was lower in 2% FBS medium, but increased with addition of VEGF. Real-Time PCR showed that ASCs maintained most of their stemness and angiogenic genes' expression in 10% FBS at P1, P5 and P6, but this increased significantly in 2% FBS at P6. Endogenic genes expression such as PECAM-1, VE chaderin and VEGFR-2 decreased after serial passage in 10% FBS, but increased significantly at P6 in 2% FBS. Addition of VEGF did not cause any significant change in gene expression level.
CONCLUSION: Adipose stromal cells had greater angiogenic potential when cultured in reduced serum conditions. VEGF did not enhance their angiogenic potential in 2% FBS-supplemented medium.
METHODS: Diabetic rats were treated orally with the vehicle or the ginger extract (75 mg/kg/day) over a period of 24 weeks along with regular monitoring of bodyweight and blood glucose and weekly fundus photography. At the end of the 24-week treatment, the retinas were isolated for histopathological examination under a light microscope, transmission electron microscopy, and determination of the retinal tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-κB), and vascular endothelial growth factor (VEGF) levels.
RESULTS: Oral administration of the ginger extract resulted in significant reduction of hyperglycemia, the diameter of the retinal vessels, and vascular basement membrane thickness. Improvement in the architecture of the retinal vasculature was associated with significantly reduced expression of NF-κB and reduced activity of TNF-α and VEGF in the retinal tissue in the ginger extract-treated group compared to the vehicle-treated group.
CONCLUSIONS: The current study showed that ginger extract containing 5% of 6-gingerol attenuates the retinal microvascular changes in rats with streptozotocin-induced diabetes through anti-inflammatory and antiangiogenic actions. Although precise molecular targets remain to be determined, 6-gingerol seems to be a potential candidate for further investigation.
METHODS: Blood from 30 patients with primary OSCC and 1:1 age-sex-matched controls was subjected to qPCR and ELISA to detect VEGF-A gene expression and serum level. Tumors of the 30 patients were investigated for VEGF Receptor-2 (VEGFR-2) expression and were analyzed using Image J software version 1.52 for DAB percentage (DAB-P) area and optical density (OD).
RESULTS: VEGF-A relative gene expression among patients was 2.43-fold higher compared to the healthy control group. Well-differentiated had a 1.98-fold increment, while poorly differentiated had a 3.58-fold increment. Serum VEGF-A was significantly elevated among the patients compared to controls (458.7 vs 253.2, p=0.0225). Poorly differentiated had a higher serum VEGF concentration (1262.0±354.7pg/ml) compared with other two. Mean VEGFR-2 DAB-P level in OSCC was 42.41±5.61(p=0.15). Well-differentiated had a DAB-P of 41.20±5.32 while poorly differentiated had DAB-P 46.21±3.78. The mean OD in OSCC was 0.54±0.16. VEGFR-2 OD in well and poorly differentiated OSCC were 0.48±0.12 and 0.68±0.17, respectively.
CONCLUSIONS: VEGF-A gene expression, serum levels, and tissue VEGFR-2 levels correlated linearly with the stage and grade of the tumor. This study justifies the value of VEGF-A as a potential biomarker in OSCC in early detection of OSCC. More studies are needed to accept the use of VEGF-A.
METHODS: Non-interventional multicenter historical cohort study of intravitreal ranibizumab use for nAMD in routine clinical practice between April 2010 and April 2013. Eligible patients were diagnosed with nAMD, received at least one intravitreal ranibizumab injection during the study period, and had been observed for a minimum of 1 year (up to 3 years). Reimbursement scenarios were defined as self-paid, partially-reimbursed, and fully-reimbursed.
RESULTS: More than three-fourths (n = 2521) of the analysis population was partially-reimbursed for ranibizumab, while 16.4% (n = 532) was fully-reimbursed, and 5.8% was self-paid (n = 188). The average annual ranibizumab injection frequency was 4.1 injections in the partially-reimbursed, 4.7 in the fully-reimbursed and 2.6 in the self-paid populations. The average clinical monitoring frequency was estimated to be 6.7 visits/year, with similar frequencies observed across reimbursement categories. On average, patients experienced VA reduction of -0.7 letters and a decrease in CRT of -44.4 μm. The greatest mean CRT change was observed in the self-paid group, with -92.6 μm.
CONCLUSIONS: UNCOVER included a large, heterogeneous ranibizumab-treated nAMD population in real-world settings. Patients in all reimbursement scenarios attained vision stability on average, indicating control of disease activity.
MATERIALS & METHODS: The fabricated core/shell nanofibers contained polycaprolactone/gelatin as the shell, and silk fibroin/VEGF as the core materials.
RESULTS: The results observed that the core/shell nanofibers interact to differentiate MSCs into smooth muscle cells by the expression of vascular smooth muscle cell (VSMC) contractile proteins α-actinin, myosin and F-actin.
CONCLUSION: The functionalized polycaprolactone/gelatin/silk fibroin/VEGF (250 ng) core/shell nanofibers were fabricated for the controlled release of VEGF in a persistent manner for the differentiation of MSCs into smooth muscle cells for vascular tissue engineering.
BIOLOGICAL SIGNIFICANCE: Comprehensive venom proteomes of D. russelii from different locales will facilitate better understanding of the geographical variability of the venom in both qualitative and quantitative terms. This is essential to provide scientific basis for the interpretation of differences in the clinical presentation of Russell's viper envenomation. The study revealed a unique venom proteome of the Pakistani D. russelii from the wild (Indus Delta), in which PLA2 predominated (~60% of total venom proteins). The finding unveiled remarkable differences in the venom compositions between the wild (present study) and the captive specimens reported previously. The integration of toxicity tests enabled the correlation of the venom proteome with the envenoming pathophysiology, where the venom showed potent lethality mediated through coagulopathic activity. The Indian VINS Polyvalent Antivenom (VPAV) showed binding activity toward the venom protein antigens; however the immunorecognition of small proteins and PLA2-dominating fractions was low to moderate. Consistently, the antivenom neutralized the toxicity of the wild Pakistani Russell's viper venom at moderate efficacies. Our results suggest that it may be possible to enhance the Indian antivenom potency against the Pakistani viper venom by the inclusion of venoms from a wider geographical range including that from Pakistan into the immunogen formulation.
AIMS: To investigate P. niruri leaves aqueous extract (PN) effects on kidney functions, histopathological changes and levels of oxidative stress, inflammation, fibrosis, apoptosis and proliferation in DM.
METHODS: PN was orally administered to streptozotocin-nicotinamide-induced male diabetic rats for 28 days. At the end of the treatment, fasting blood glucose (FBG) and kidney functions were measured. Kidney somatic index, histopathological changes and levels of RAGE, Nrf2, oxidative stress markers (TBARS, SOD, CAT and GPx), inflammatory markers (NFkβ-p65, Ikk-β, TNF-α, IL-1β and IL-6), apoptosis markers (caspase-3, caspase-9 and Bax), fibrosis markers (TGF-β1, VEGF and FGF-1) and proliferative markers (PCNA and Ki-67) were determined by biochemical assays, qPCR, Western blotting, immunohistochemistry or immunofluorescence.
RESULTS: Administration of PN helps to maintain near normal FBG, creatinine clearance (CCr), blood urea nitrogen (BUN), BUN/Cr ratio, serum electrolytes, uric acid and urine protein levels in DM. Decreased RAGE, TBARS and increased Nrf2, SOD-1, CAT and GPx-1 were observed in PN-treated diabetic rat kidneys. Expression of inflammatory, fibrosis and apoptosis markers in the kidney reduced but expression of proliferative markers increased following PN treatment. Lesser histopathological changes were observed in the kidney of PN-treated diabetic rats.
CONCLUSION: PN helps to preserve near normal kidney function and prevents histopathological changes via ameliorating oxidative stress, inflammation, fibrosis and apoptosis while enhancing proliferation of the kidney in DM.