Capillary Proliferation Research Articles

MANAGEMENT OF PAPILLARY RETINAL CAPILLARY HEMANGIOMAS - CASE REPORT AND REVIEW OF LITERATURE

Background: Retinal capillary hemangiomas (RCH) are rare, benign, vascular tumours characterized by capillary andglial cell proliferation. We report the management of a patient with a unilateral endophytic papillary RCH withexudations and serous retinal detachment.Methods: Case reportResults: A 46-year old female presented with papillary RCH without association with von Hippel-Lindau syndrome.She was given two doses of intravitreal bevacizumab following which the serous detachment resolved. When theedema recurred again, she was given a dose of 4mg intravitreal triamcinolone acetate. The edema resolved and didnot recur till the end of three months. She was given the option of photodynamic therapy, however, she did notconsent for the procedure due to the high costs involved.Conclusion: Intravitreal injections can be used as a temporary remedy for the treatment of macular edema causedby RCH. However, currently there is no ideal definitive treatment available for papillary RCH. Larger studies arenecessary to establish the treatment for this condition.

Biological acellular pericardial mesh regulated tissue integration and remodeling in a rat model of breast prosthetic implantation.

The use of biological meshes has proven beneficial in surgical restriction and periprosthetic capsular contracture following breast prosthetic-reconstruction. Three different types (smooth, texturized, and polyurethane) of silicone round mini prostheses were implanted under rat skin with or without two different bovine acellular pericardial biological meshes (APMs, BioRipar, and Tutomesh). One hundred eighty-six female rats were divided into 12 groups, sacrificed after 3, 6, and 24 weeks and tissue samples investigated by histology and immunohistochemistry. Implantation of both APMs, with or without prostheses, reduced capsular α-SMA expression and CD3+ inflammatory cell infiltration, increasing capillary density and cell proliferation, with some differences. In particular, Tutomesh was associated with higher peri-APM CD3+ inflammation, prosthetic capsular dermal α-SMA expression and less CD31+ vessels and cell proliferation compared with BioRipar. None differences were observed in tissue integration and remodeling following the APM + prostheses implantation; the different prostheses did not influence tissue remodeling. The aim of our study was to investigate if/how the use of different APMs, with peculiar intrinsic characteristics, may influence tissue integration. The structure of APMs critically influenced tissue remodeling after implantation. Further studies are needed to develop new APMs able to optimize tissue integration and neoangiogenesis minimizing periprosthetic inflammation and fibrosis.

황련 추출물의 아토피피부염 유발 생쥐에서 피부손상 완화 효과

This study aims to evaluate the anti-inflammatory effect of Coptidis Rhizoma (CR) extract for atopic dermatitis through maintaining skin barrier and regulating Th2 cell differentiation. We divided NC/Nga mice into 3 groups as follows; atopy-like dermatitis induced group with CR treatment (CT, n=10), no treatment group(Ctrl), atopy-like dermatitis elicited group(AE). Atopy-like dermatitis was induced to NC/Nga mice by sensitizing with dermatophagoides farinae(DfE) on 7, 8, 9, 11, 12, and 13th week. After inducing atopic dermatitis, CR extract was administered 20 mg/kg daily for the experimental duration to the CT group. We measured the integrity of lipid layers in the epidermis and Th2 differentiation through immunohistochemical staining against filaggrin, loricrin, IL-4, and IL-13. We also measured the distribution of subcutaneous collagen fibers by the Massons trichrome staining. Administration of CR significantly inhibited the reduction of lipid layers in the skin that caused atopy. The expression of IL-4, IL-13, each of which is a cytokine secreted by T helper type 2 (Th2) cells, was markedly suppressed in the CT group as compared with AE group (p<0.05). CR treatment also decreased the expression of iNOS, p-IκB. Atopic dermatitis induced dermatological damage to skin, such as hyperplasia of epithelium, and capillary proliferation was significantly reduced by CR administration. CR effectively inhibited the thinning of the skin barrier and inflammatory responses in atopic dermatitis-induced mice. In particular, it showed anti-inflammatory effects by reducing the expression of IL-4 and IL-13, Th2 cell cytokines, which play a crucial role in development of atopic dermatitis. Therefore, CR can be a good candidate to ameliorate and treat atopic dermatitis.

MicroRNA‑576‑3p inhibits the migration and proangiogenic abilities of hypoxia‑treated glioma cells through hypoxia‑inducible factor‑1α.

The most common and aggressive type of brain cancer in adults is glioblastoma multiforme (GBM), and hypoxia is a common feature of glioblastoma. As the histological features of glioma include capillary endothelial cell proliferation, they are highly prone to invading the surrounding normal brain tissue, which is often one of the reasons for the failure of treatment. However, the mechanisms involved in this process are not fully understood. MicroRNAs (miRs) are a class of non-coding RNA that are able to inhibit the malignant progression of tumor cells through the regulation of downstream genes. In the present study, the low expression of miR-576-3p was detected in glioma samples and hypoxia-treated glioma cells using a reverse transcription-quantitative polymerase chain reaction. The present study focused on the effects of miR-576-3p on hypoxia-induced glioma. The results of the functional experiments revealed that the overexpression of miR-576-3p significantly inhibited the migration and pro-angiogenic abilities of the glioma cells under hypoxic conditions (P<0.05) compared with in the lentivirus-miR-negative control group. Furthermore, luciferase reporter gene assays were used to validate the hypothesis that miR-576-3p interacts with the 3′-untranslated region of hypoxia-inducible factor-1α (HIF-1α) and induces a reduction in the protein levels of matrix metalloproteinase-2 and vascular endothelial growth factor. Rescue experiments demonstrated that the restoration of HIF-1α expression attenuated the effect of miR-576-3p on the migration and proangiogenic abilities of glioma cells. In conclusion, the present study confirms that miR-576-3p is a novel GBM inhibitor and its inhibition of the migration and proangiogenic capacity of hypoxia-induced glioma cells is mediated by HIF-1α.

Expression Pattern of Angiogenic Factors in Healthy Heart in Response to Physical Exercise Intensity.

Recently, many studies showing the regeneration potential of both cardiac and hematopoietic stem cells in adult heart following injury were definitively retracted by the literature. Therefore, stimulating myocardial angiogenesis becomes to be important for preventing cardiovascular diseases. Regular endurance exercise has been reported to induce capillary growth in healthy and diseased myocardium resulting in cardioprotective phenotype. Previously, we demonstrated a significantly increased capillary proliferation in mouse hearts following 30 and 45 days of endurance training. In the present study, we examined the localization and expression pattern of vascular endothelial growth factor receptors (VEGFR-1/Flt-1 and VEGFR-2/Flk-1), hypoxia-inducible factor-1α (HIF-1α), and inducible nitric oxide synthase (iNOS) in heart neocapillarization in response to a mild, moderate, and high intensity of endurance training. Sixty-three Swiss male mice were divided into four untrained control groups and three groups trained for 15 (T15), 30 (T30), and 45 (T45) days with a gradually increasing intensity on a treadmill. We observed the localization of studied proteins with immunostaining and their expression level with Western blot analyses. We found that VEGFR-2/Flk-1 expression progressively increased in trained groups compared with controls, while VEGFR-1/Flt-1 and HIF-1α were higher in T15 than in controls, T30, and T45 animals. Differently, iNOS levels enhanced after 15 and 30 days of exercise. The localization of these factors was not altered by exercise. The results showed that the expression of VEGFR-1/Flt-1, VEGFR-2/Flk-1, HIF-1α, and iNOS is differently regulated in cardiac angiogenesis according to the exercise intensity. VEGFR-1/Flt-1 and HIF-1α are upregulated by a mild intensity exercise, while VEGFR-2/Flk-1 progressively enhances with increasing workload. Differently, iNOS protein is modulated by a moderate intensity exercise. VEGF pathway appears to be involved in exercise-related angiogenesis in heart and VEGF might act in a paracrine and endocrine manner. Understanding this relationship is important for developing exercise strategies to protect the heart by insults.

Capillary Proliferation in Systemic-Sclerosis-Related Pulmonary Fibrosis: Association with Pulmonary Hypertension.

ObjectiveWe sought to determine if any histopathologic component of the pulmonary microcirculation can distinguish systemic sclerosis (SSc)‐related pulmonary fibrosis (PF) with and without pulmonary hypertension (PH).MethodsTwo pulmonary pathologists blindly evaluated 360 histologic slides from lungs of 31 SSc‐PF explants or autopsies with (n = 22) and without (n = 9) PH. The presence of abnormal small arteries, veins, and capillaries (pulmonary microcirculation) was semiquantitatively assessed in areas of preserved lung architecture. Capillary proliferation (CP) within the alveolar walls was measured by its distribution, extent (CP % involvement), and maximum number of layers (maximum CP). These measures were then evaluated to determine the strength of their association with right heart catheterization–proven PH.ResultsUsing consensus measures, all measures of CP were significantly associated with PH. Maximum CP had the strongest association with PH (P = 0.013; C statistic 0.869). Maximum CP 2 or more layers and CP % involvement 10% or greater were the optimal thresholds that predicted PH, both with a sensitivity of 56% and specificity of 91%. The CP was typically multifocal rather than focal or diffuse and was associated with a background pattern of usual interstitial pneumonia. There was a significant but weaker relationship between the presence of abnormal small arteries and veins and PH.ConclusionIn the setting of advanced SSc‐PF, the histopathologic feature of the pulmonary microcirculation best associated with PH was capillary proliferation in architecturally preserved lung areas.

Subconjunctival Bevacizumab for Recurrent Conjunctival Pyogenic Granuloma

A 45-year-old male presented with a pyogenic granuloma of the bulbar conjunctiva of the left eye following a stick injury. It was a benign friable, hyperplastic, vascular lesion comprised of inflammatory cells and lobular capillary proliferation. The differential diagnosis includes squamous papillomas, hemangiomas, suture granulomas, and ocular surface tumors, such as squamous cell carcinoma and amelanotic melanoma. Conventional treatment includes topical corticosteroids and surgical excision. Treatment of recurrent lesions with cryotherapy, electrocautery, topical antimetabolites, and plaque irradiation has been described. We present a case of recurrent pyogenic granuloma successfully treated with two subconjunctival bevacizumab injections. The patient developed three recurrences after excision at a peripheral hospital after which he was successfully treated with excision and adjuvant subconjunctival bevacizumab 2.5 mg/0.1 ml injection. This case highlights the novel use of bevacizumab for recurrent pyogenic granuloma.

Comprehensive three-dimensional morphology of neoangiogenesis in pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis.

Pulmonary veno‐occlusive disease (PVOD) is a rare lung disease characterized by fibrotic narrowing of pulmonary veins leading to pulmonary hypertension (PH) and finally to death by right heart failure. PVOD is often accompanied by pulmonary capillary hemangiomatosis (PCH), a marked abnormal proliferation of pulmonary capillaries. Both morphological patterns often occur together and are thought to be distinct manifestations of the same disease process and accordingly are classified together in group 1′ of the Nice classification of PH. The underlying mechanisms of these aberrant remodeling processes remain poorly understood. In this study, we investigated the three‐dimensional structure of these vascular lesions in the lung explant of a patient diagnosed with PVOD by μ‐computed tomography, microvascular corrosion casting, electron microscopy, immunohistochemistry, correlative light microscopy and gene expression analysis. We were able to describe multifocal intussusceptive neoangiogenesis and vascular sprouting as the three‐dimensional correlate of progressive PCH, a process dividing pre‐existing vessels by intravascular pillar formation previously only known from embryogenesis and tumor neoangiogenesis. Our findings suggest that venous occlusions in PVOD increase shear and stretching forces in the pulmonary capillary bloodstream and thereby induce intussusceptive neoangiogenesis. These findings can serve as a basis for novel approaches to the analysis of PVOD.

Focal Chorangiosis: Does It Have Clinical and Pathologic Significance?

Chorangiosis is a proliferation of capillaries in terminal chorionic villi and is considered to be a marker for hypoxia and poor clinical outcome. Not all cases with hypervascular villi meet the generally accepted diagnostic criteria as reported by Altshuler. Our aim was to evaluate cases with villous hypervascularity that do not meet the diagnosis of chorangiosis, in which increased vascularity was present in a significant portion of the villous tissue but was not a diffuse process, which we call focal chorangiosis, to ascertain whether there were clinical or pathologic associations. A total of 175 placentas with the finding of focal chorangiosis and 176 maternal age- and gestational age-matched controls were evaluated retrospectively. We defined focal chorangiosis as villous hypervascularity that did not meet criteria for a diagnosis of chorangiosis, but in which there was involvement of at least 50% of villi on at least 2 of 3 slides of placental tissue or involvement of all the villi on 1 slide. In these focal areas, the criteria of 10 capillaries in each of 10 villi in ten 10× microscopic fields were required. We found that focal chorangiosis is associated with a decrease in Apgar scores, increased placental weight, fetal vascular thrombosis (fetal vascular malperfusion), umbilical cord abnormalities, increased fetal nucleated red blood cells, villous dysmaturity, and increased rate of vaginal delivery. Many of these associations are shared with chorangiosis as traditionally defined, suggesting that focal chorangiosis is a significant finding that should be reported.

Assessment of Antioxidant and Antiangiogenic Activities of Ethanolic Root extract of Cassia occidentalis

Context: The process by which new blood vessels grow is termed as Angiogenesis. In the adult, except for a few physiological processes such as menses, wound healing, and placental formation, all angiogenic processes are pathologic. Angiogenic imbalance in which proangiogenic factors predominate over antiangiogenic factors is tumor angiogenesis. Inhibition of blood vessel growth, is a way to prevent tumour growth and other angiogenesis-dependent diseases is antiangiogenesis. Aim: The present study aims to determine the antioxidant and antiangiogenic activities of ethanolic root extract of Cassia occidentalis. Materials and methods: Antioxidant activity was evaluated against various free radicals like Nitric oxide scavenging, Hydroxyl radicals and Phosphomolybdenum assay using Ascorbic acid as standard. The most common study used to evaluate the antiangiogenic activity is chick embryo chorioallantoic membrane (CAM) , an in vivo assay. Results: Ethanolic root extract of Cassia occidentalis exhibited a significant antioxidant status which is evident from their IC50 values 21.42 ug/mL in Nitric oxide scavenging method, 22.3 ug/mL in hydroxyl radical. In phosphomolybdenum assay, there is concentration-dependent increase in absorbance. The results obtained are similar to that of standard drug ascorbic acid. In anti-oxidant activity, percentage inhibition was determined by calculating IC50 values . By decreasing the capillary networks proliferation in a dose (50 to 150 µg/egg) dependent manner which is probably related to the inhibition of neovascularization. The present study results indicated significant antiangiogenic effect on chorioallantoic membrane. Conclusion: The plant extract has shown good free radical scavenging activity indicative from their percentage inhibition. It also exhibits significant antiangiogenic activity, and this is a possible rationale for its folkloric use as an anticancer agent.

Clinical features of canine pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis.

BackgroundHistologic features of pulmonary veno‐occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) have been described in dogs but without a thorough clinical description.ObjectivesTo report the clinical features, diagnostics, treatment, and outcome of dogs with histologic evidence of PVOD and PCH.AnimalsFifteen pet dogs meeting histopathologic criteria of PVOD (occlusive remodeling of small‐sized to medium‐sized pulmonary veins) or PCH (alveolar capillary proliferation and congestion), or both.MethodsMedical records of dogs with PVOD and PCH identified based on histopathologic features between 2003 and 2017 were retrospectively reviewed.ResultsFifteen dogs met inclusion criteria of a histologic diagnosis of PVOD or PCH or both. Dogs were older (median 11 years) with no apparent breed or sex predisposition. Dogs presented with acute clinical signs (median 3 days), usually respiratory distress. Thoracic radiography (available in 10 dogs) revealed right cardiomegaly and patchy or diffuse interstitial to alveolar patterns, with 9 dogs having a normal left cardiac silhouette. In 5 dogs tested, pulmonary arterial hypertension (PAH) was documented. In all 3 dogs, thoracic computed tomography scans showed pulmonary arterial enlargement and perivascular diffuse nodular ground‐glass opacities. Ten of 15 dogs died within 1 day; median survival was 3 days.Conclusions and Clinical ImportanceIn dogs with PAH, the inability to document left‐sided congestive heart failure and failure to identify another cause of signs of respiratory disease should increase suspicion for PVOD and PCH. With increased awareness of PVOD and PCH by clinicians and pathologists, dogs with compatible clinicopathologic features should be evaluated for these pulmonary vascular disorders.

Abstract 16750: Angiogenesis/Arteriogenesis, the Mechanism for Cardioprotection, in Secreted Frizzled Related Protein 2 Transgenic Mice

Secreted frizzled related protein 2 (sFRP2) has been shown to protect against myocardial ischemia primarily mediated by reducing fibrosis. Our hypothesis is that sFRP2 myocardial ischemic protection induced by permanent coronary artery occlusion (CAO) must involve a primary angiogenesis/arteriogenesis mechanism in order to protect the heart in the chronic absence of blood flow. To test this hypothesis, we induced permanent CAO for 1 week in cardiac specific sFRP2 transgenic (TG) mice (n=12), which exhibited reduced infarct size vs. their wild type littermates (WTL; n=13) (16±1 vs. 25±2%) and improved left ventricular ejection fraction (LVEF) (61±6 vs. 45±6%). These salutary effects were accompanied by angiogenesis (170% increase in capillary proliferation and a 54% increase in capillary density) and arteriogenesis (106% increase in arteriole proliferation). sFRP2 increased in vitro tubule formation in HUVEC cells by 46% (p&lt;0.05), compared to vehicle. As expected, sFRP2 TG mice also exhibited decreased remote fibrosis, compared to WTL (1.6±0.1 vs.± 3.7±0.3%; n=4-6/group). ATF6, an ER stress response transcription factor, was upregulated in sFRP2 TG mice. When ATF6 was blocked with AEBSF, sFRP2 TG mice no longer demonstrated cardioprotection with permanent CAO, as reflected by similar infarct size, LV EF, capillary and arteriolar proliferation observed in WTL. cTGF, a pro-angiogenic factor, was also upregulated in sFRP2 TG mice. Blocking cTGF with a cTGF antibody, eliminated the increased tubule formation with sFRP2 treatment. AEBSF also eliminated the increased cTGF in sFRP2 TG, confirming ATF6 as the upstream regulator of cTGF, responsible for the angiogenesis and arteriogenesis observed in the sFRP2 TG mice. To determine if angiogenesis/arteriogenesis was the initiating mechanism inducing cardioprotection, blood flow, measured ultrasonically at 1 day following CAO, was increased significantly more, p&lt;0.05, in the ischemic zone of sFRP2 TG mice (2.1±0.46 A.U.) compared with blood flow in WTL (0.4 ±0.09 A.U.). Thus, angiogenesis/arteriogenesis appears to be the primary cardioprotective mechanism induced by sFRP2, with reduced fibrosis playing a secondary role.

A Rare Cause of Anemia and Abdominal Pain in an HIV-Positive Patient

47 year old Hispanic male with HIV since 2000 on emtricitabine-tenofovir and dolutegravir with past history of Shigella sp enterocolitis and prostatitis, GERD on omeprazole. He was referred for endoscopy due to two 2 cm polypoid lesions in gastric fundus found through work up of chronic abdominal pain and bloating. Patient had intermittent compliance with anti-viral and CD4 counts fluctuated between 324 and 22. He had normocytic anemia (Hematocrit 31.1, MCV 86.9). Quantiferon TB, syphilis RPR, JC virus were negative. Two 20 mm pedunculated polyps with bleeding stigmata were found (gastric cardia and body) and removed via endoscopic mucosal resection. Histologically, they had lobular proliferation of cytologically bland capillaries with surface erosion and neutrophil infiltrate consistent with pyogenic granuloma. Additionally, Helicobacter pylori and CMV immune-stains were positive. There was no intestinal metaplasia, dysplasia or carcinoma. Pyogenic granuloma is a benign highly vascular tumor with friable surface which bleeds on contact. It is rarely found in the GI tract outside of the oral cavity. Proposed causes are reaction to chronic mucosal trauma or inflammation/ infection. Pyogenic granulomas of the GI tract are important cause of blood loss anemia. In HIV patients, they are known to occur in skin and oral mucosa and should be differentiated histologically from Kaposi's sarcoma. Treatment involves endoscopic mucosal resection and there is risk for post-procedural bleeding.2033_A Figure 1. A: Polyp in gastric cardia C: Neutrophilic infiltrate surrounds capillaries2033_B Figure 2. B: Lobular capillary proliferation

Thioredoxin-1 augments wound healing and promote angiogenesis in a murine ischemic full-thickness wound model

BackgroundNonhealing wounds are a continuing health problem in the United States. Overproduction of reactive oxygen species is a major causative factor behind delayed wound healing. Previously we reported that thioredoxin-1 treatment could alleviate oxidative stress under ischemic conditions, such as myocardial infarction and hindlimb ischemia. In this study, we explored the potential for thioredoxin-1 gene therapy to effectively aid wound healing through improved angiogenesis in a murine ischemic wound model. MethodsFull-thickness, cutaneous, ischemic wounds were created in the dorsum skin flap of 8- to 12-week-old CD1 mice. Nonischemic wounds created lateral to the ischemic skin flap served as internal controls. Mice with both ischemic wounds and nonischemic wounds were treated with Adeno-LacZ (1 × 109 pfu) or Adeno-thioredoxin-1 (1 × 109 pfu), injected intradermally around the wound. Digital imaging was performed on days 0, 3, 6, and 9 to assess the rate of wound closure. Tissue samples collected at predetermined time intervals were processed for immunohistochemical analysis. ResultsNo significant differences in wound closure were identified among the nonischemic wounds control, nonischemic wounds-LacZ, and nonischemic wounds–thioredoxin-1 groups. Hence, only mice with ischemic wounds were further analyzed. The ischemic wounds–thioredoxin-1 group had significant improvement in wound closure on days 6 and 9 after surgery compared with the ischemic wounds control and ischemic wounds-LacZ groups. Immunohistochemical analysis indicated increased thioredoxin-1, vascular endothelial cell growth factor, and β-catenin levels in the ischemic wounds–thioredoxin-1 group compared with the ischemic wounds control and ischemic wounds-LacZ groups, as well as increased capillary density and cell proliferation, as represented by Ki-67 staining. ConclusionTaken together, thioredoxin-1 gene therapy promotes vascular endothelial cell growth factor signaling and re-epithelialization and activates wound closure in mice with ischemic wounds.

Anti-angiogenic effects of the DPP-4 inhibitor linagliptin via inhibition of VEGFR signalling in the mouse model of oxygen-induced retinopathy.

Linagliptin has protective effects on the retinal neurovascular unit but, in proliferative retinopathy, dipeptidyl peptidase 4 (DPP-4) inhibition could be detrimental. The aim of this study was to assess the effect of linagliptin on ischaemia-induced neovascularisation of the retina. C57BL/6J and glucagon-like peptide 1 (GLP-1) receptor (Glp1r)-/- mice were subjected to a model of oxygen-induced retinopathy (OIR). Both strains were subcutaneously treated with linagliptin from postnatal days 12 to 16. Non-injected OIR and non-exposed mice served as controls. Capillary proliferations and systemic levels of active GLP-1 were quantified. The effects of linagliptin on vascular endothelial growth factor (VEGF)-induced downstream signalling were assessed in human umbilical vein endothelial cells (HUVECs) using western blot for retinal phosphorylated extracellular signal-regulated kinase (ERK)1/2 and retinal gene expression analyses. Linagliptin treatment led to an increase in active GLP-1 and a decreased number of neovascular nuclei in OIR mice vs controls (-30%, p < 0.05). As the reduction in neovascularisation was similar in both C57BL/6J and Glp1r-/- mice, the anti-angiogenic effects of linagliptin were independent of GLP-1R status. The expression of Vegf (also known as Vegfa) and Hif1a was increased in C57BL/6J OIR mice upon linagliptin treatment (three- vs 1.5-fold, p < 0.05, p < 0.01, respectively). In HUVECs, linagliptin inhibited VEGF-induced increases in mitogen-activated protein kinase (MAPK)/ERK (-67%, p < 0.001) and MAPK/c-Jun N-terminal kinase (JNK) (-13%, p < 0.05) pathway activities. In the retinas of C57BL/6J mice, p-ERK1/2 levels were significantly reduced upon linagliptin treatment (-47%, p < 0.05). Systemic treatment with linagliptin demonstrated GLP-1R-independent anti-angiogenic effects mediated by an inhibition of VEGF receptor downstream signalling. The specific effects of linagliptin on diabetic retinopathy are of potential benefit for individuals with diabetes, independent of metabolic effects.

Tigecycline as a dual inhibitor of retinoblastoma and angiogenesis via inducing mitochondrial dysfunctions and oxidative damage

Retinoblastoma is the most common intraocular malignancy in children with poor prognosis. The progression of retinoblastoma is dependent on a robust angiogenic response. Targeting both retinoblastoma cells and angiogenesis may therefore provide an alternative therapeutic strategy in retinoblastoma. Here, we demonstrated the inhibitory effects of tigecycline, a FDA-approved antibiotic, in retinoblastoma and angiogenesis in vitro and in vivo. We showed that tigecycline significantly inhibited growth and induced caspase-dependent apoptosis of multiple retinoblastoma cell lines. Tigecycline also effectively inhibited angiogenesis through suppressing capillary network formation, migration, proliferation and survival of human retinal microvascular endothelial cell (HREC). Mechanistically, tigecycline acts on both retinoblastoma cells and HREC via inhibiting mitochondrial protein translation, resulting in mitochondrial dysfunction, energy crisis, and oxidative damage. Importantly, we demonstrated the in vivo efficacy of tigecycline in inhibiting retinoblastoma and angiogenesis, and inducing oxidative stress on xenograft mouse model. In addition, ATP levels and growth rates were largely affected in retinoblastoma ρ0 cells that lacked mitochondrial respiration. Our work provides systematic pre-clinical evidence for repurposing tigecycline from its traditional use for retinoblastoma treatment. Our work demonstrates the essential roles of mitochondrial metabolism in both retinoblastoma and its angiogenesis.

A case of glomerulonephritis showing remarkable segmental extracapillary proliferation; Is this a new category disease or not?

Background: Significant capillary proliferation is common in post-streptococcal acute glomerulonephritis (PSAGN) after streptococci and is a prognostic disease. Focal segmental glomerulosclerosis is a disease characterized by segmental sclerosis although it may have a poor prognosis Case Presentation: A 50-year-old man with nephrotic syndrome underwent renal biopsy, which showed marked endocapillary proliferation due to enlarged vascular endothelial cells and infiltration of lymphocytes. However, there was no mesangial cell proliferation, mesangial matrix increase, or crescent formation. Electron microscopy showed fusion of podocytes without any electron-dense deposits. Immunostaining for CD68 and CD3 was positive, and the presence of macrophages and T-cells was suggested. Steroid therapy, including pulse therapy, was performed, and then cyclosporine was added to steroid therapy. Although urinary protein decreased, his renal function did not respond well to steroid therapy, and the patient initiated dialysis 2 years later. Conclusions: We report this case considering that it was nephritis of unknown origin showing segmental endocapillary proliferation that had not been recognized previously.

Topically applied hypericin exhibits skin penetrability on nude mice.

Hypericin, a powerful natural photosensitizer in photodynamic therapy (PDT), is suitable for treating skin diseases involving excess capillary proliferation. In the present study, we aimed to evaluate the skin penetrability of topically applied hypericin, expecting a reduced risk of prolonged skin photosensitivity, which often occurs after systemic administration. Firstly, the Franz diffusion cell assays were performed to evaluate the penetration effects of different enhancers, including menthol, propylene glycol, camphanone, azone, and carbamide. In view of above evaluation results, we selected menthol as the enhancer in the subsequent in vivo studies. The setting groups were as follows: the blank control group, the light-exposure control group, the gel-base control group, the hypericin gel group, and a hypericin gel-containing menthol group. Except for the blank control, all other animals were irradiated by a LED light. Then, fluorescence microscopy was performed to examine the distribution of hypericin in the skin of nude mouse. Macroscopic and microscopic analyses were also carried out to detect pathological changes in the skin after topical hypericin-PDT treatment. Immunohistochemistry was used to determine the expression change of PECAM-1. As shown in the results, menthol facilitated hypericin penetrate the skin of nude mice most. The results of in vivo assays revealed that hypericin penetrated nude mouse skin, spread to the dermis, and resulted in obvious photosensitivity reaction on the dermal capillaries. Moreover, skin injured by the photosensitive reaction induced by hypericin-PDT treatment was replaced by normal skin within 7days. We concluded that topical applied hypericin could penetrate nude mouse skin well and has a great potential in PDT treatment of skin diseases.

Hydrops Fetalis and Congenital Pulmonary Capillary Haemangiomatosis in a Premature Infant - A Case Report and Literature Review

Abstract Pulmonary capillary haemangiomatosis (PCH) is a rare disorder of the lung, well described in adult literature. PCH is characterized by capillary proliferation, infiltrating the interstitium and alveolar walls. This leads to development of respiratory distress and to end-stage pulmonary hypertension. Mostly young adults are affected. The affection of newborn is described in less than ten cases in literature in the past forty years. PCH is a mostly deadly ending disease. We present a preterm born infant with antepartal diagnosed hydrops fetalis, who died 30 minutes after birth. Autopsy revealed PCH as lethal reason and not cardial disease as presumed before.

The impact of iron deficiency anemia on histomorphological features of placenta and the newborn infants.

Iron deficiency anemia during pregnancy ismutual heamatological disorder that happens in pregnancy,it affects maternal blood, leading to hypoxia,which cause changes in the structure of the placenta. Aim of study to explore the changes occurres bothin gross morphology and in histology of the placenta in anemic mothers. Methods: A fifty placentas were taken from mothers (full term) delivered at hospital constituted the material for thepresent study. Full term placentawas collected with case history and investigated after delivery of fetus. Two cm pieces were removed from both anemic and normalgroup of placenta fixed in 10% formalin and used for processing and staining.The microscopic study revealed histomorphological abnormalities as increased capillaries per villas,thickening of capillary basement membrane, trophoblastic basementmembrane,cytotrophoplastic proliferation, syncytial knots and fibrosis. All these changes occurred maintaining sufficient efficiency of placenta,to fulfill demand of oxgen in the fetus.