Estimation of the level of endothelial factor of vascular growth and monocytic chemoattractant in children cerebral palsy

Objective. The aim of this article is to assess the role of vascular endothelial growth factor and monocytic chemoattractant in the development of cerebral palsy in children. Materials and methods. Examination of 77 children with different clinical forms of infantile cerebral palsy in the age group from 1 to 16 years was carried out. The content of monocyte chemoattractant (MCP) and vascular growth factor (VEGF) was determined in different forms of cerebral palsy. The obtained data were processed statistically. Results. The analysis of the obtained data revealed a significant increase in the indicators of monocytic chemoattractant and vascular growth factor in children with infantile cerebral palsy compared with healthy children. There were no significant differences between the indicators of MCP and VEGF in children with cerebral palsy and comorbid pathology and children with cerebral palsy without concomitant pathology. Conclusion. The authors of the presented analysis conclude that the determination of monocytic chemoattractant and vascular growth factor has a high diagnostic value for identifying a predisposition to the development of cerebral palsy. Timely detection of an increase in the level of these factors provides a broader prospective for early diagnosis of the disease and for the early implementation of rehabilitation measures accordingly.

Effectiveness and safety of 0.5% timolol solution in the treatment of pyogenic granuloma: A randomized, double-blind and placebo-controlled study

Introduction: Pyogenic granulomas are benign vascular lesions of the skin and mucosa which are often a source of concern because of their recurrent bleeding even with minimal trauma. Current treatment for pyogenic granuloma is ablative; no medical therapy is standardized to date. Timolol, due to its vasoconstrictive effect, vascular growth factor inhibition and apoptosis promotion properties, is a potential therapeutic option. Objectives: To assess the effectiveness and safety of topical timolol in the treatment of pyogenic granulomas. Methods: A two-centre, double-blind and placebo-controlled trial (Registration CTRI/2019/04/018581) was conducted. Patients of either sex were recruited with pyogenic granuloma lesions of less than eight weeks duration. Topical treatment with 0.5% timolol or matching glycerin placebo was continued for six weeks. Changes in color, size, bleeding tendency, physicians’ and patients’ global assessments and adverse events were assessed. Results: Forty subjects were randomized between the two groups which were comparable in age, sex, duration of illness and baseline lesion size.Significant improvement was noted with timolol, with color change from first follow-up onwards and lesion size reduction from second follow-up onward. Patients’ assessment of bleeding tendency also showed imrovement from the second visit onward. Between-group comparison showed significant difference with respect to percentage reduction in size (timolol 40.9%, placebo 3.4%; P = 0.002). Rescue treatment (electrosurgery) was required in five patients on placebo and in one in the timolol group (P = 0.182). Complete resolution occurred in 2 (10%) patients with timolol and in no patients on placebo (P = 0.231). Limitations: We observed effects of treatment for only six weeks. Conclusion: Topical timolol may be a treatment option for early pyogenic granulomas but complete resolution is unlikely in six weeks. Studies of longer duration are required to assess resolution and recurrence rates.

MECHANISMS OF IMMUNOCORRECTIVE ACTION OF PHOTODYNAMIC THERAPY AND EXOSOMES OF MESENCHYMAL STEM CELLS IN PATIENTS WITH CHRONIC WOUNDS OF THE LOWER EXTREMITIES OF DIFFERENT GENESIS

Summary. Introduction. The treaonic wounds of the lower extremities today requires long-term use of antibiotic therapy, which aggravates the course of the wound process. In this regard, the search for new methods of treatment is underway. Low-intensity light exposure of various wavelengths of photodynamic therapy with photosensitizer photosensitizer Dimegin was used as a physical method, and multipotent mesenchymal-stromal cells and their exometabolites in exosomes form were used as a biological method. The aim was to study the change of barrier function of oxygen-independent and oxygen-dependent phagocytosis and serum levels of vascular growth factor (VEGF) in patients with chronic wounds of the lower extremities before and after the application of complex light exposure and exosomes. Materials and methods. Phagocytosis activity of neutrophils was investigated by assessing chemotaxis, adhesion and endocytosis and by determining reactive oxygen species (ROS) in oxygen-dependent phagocytosis using light and confocal microscopy. VEGF concentration was determined by ELISA. Results: after photodynamic therapy using with red light (λ=660nm), activation of oxygen-independent and oxygen-dependent phagocytosis was observed, as well as an increase in the synthesis of vascular growth factor in patients with chronic wounds of the lower extremities. After the application of green light (λ=530nm) and the application of exosomes, the normalization of immune processes was observed, which led to the acceleration of regenerative processes in the wound. Conclusions. Thus, after carrying out complex low-intensity light therapy and exosomes, it was possible to completely clear the wounds from necrosis in a short time.

Management of patients with operated refractory neovascular glaucoma (clinical observation)

Introduction. Thrombosis (occlusion) of the central retinal vein (RCVO) and its branches is one of the main causes of loss or significant decrease in vision, including in people of working age, while RCVO is the second most common retinal vascular disease after diabetic retinopathy. The incidence rates steadily increase with age, amounting to 0.7% in the 49–60 age group and reaching 4.6% in people over 80 years old. Acute violation of retinal venous blood flow often leads to retinal ischemia, triggering the mechanism of activation of endothelial vascular growth factor (VEGF). In a quarter of patients, occlusions of the retinal veins and its branches initially proceed according to the ischemic type, which is characterized by the formation of extensive non-perfused retinal zones occupying an area of 10 or more areas of the optic nerve head (optic nerve disc) according to fluorescent angiography (FAG). In 34% of such patients, the non-ischemic type of venous occlusion becomes ischemic within 3 years.Aim. To develop an optimal algorithm for the management of patients with operated neovascular uncompensated glaucoma against the background of occlusion of the central retinal vein.Materials and methods. Two patients with operated secondary neovascular glaucoma of stage III-c. In the combined sequential therapy, the anti-VEGF medication Aflibercept (0.5 mg) was used, laser coagulation of residual newly formed vessels, laser reconstruction in the surgical area, contact transcleral cyclolazercoagulation, and laser coagulation of the peripheral parts of the retina were performed.Results. The combined sequential treatment, combined with the appointment of antihypertensive drugs in drops, allowed to stabilize the level of IOP. IOP indicators remained at the level of normal values during 1 year of follow-up.Conclusion. The use of combined laser technologies and anti-VEGF therapy allows potentiating and prolonging the hypotensive effect in the treatment of patients with operated secondary refractory neovascular glaucoma against the background of occlusion of the central retinal vein.

Features of the immunoreactivity T and B lymphocytes subpopulations and cytokine imbalance in patients with hepatosplenomegaly of different etiology

The aim was to study the mechanisms of immunological dysregulation of cytokine and immunoglobulin production, changes in the CD expression of T and B lymphocyte subpopulations in patients with hepatosplenomegaly of different etiology. Materials and methods. We examined 73 patients with liver cirrhosis complicated by portal hypertension, hepatosplenomegaly, and bleeding from phlebectasia. We identified three groups of patients depending on the triggering factors of cirrhosis: the first (I) group – HBV/HCV; the second (II) group – CMV/VEB; the third (III) group – hereditary enzymopathies. The study material was lymphocytes and blood serum. We used the methods of ELISA, immunofluorescence and flow cytometry. Results. An increase in the concentration of IgA and IgM was revealed against the background of normal number of CD22+ B lymphocytes with HBV/HCV (I group), high level of IgM and their producers, B lymphocytes, with CMV/VEB (II group), in group III with hereditary enzymopathies, the concentration of all immunoglobulins was normal with an increased content of B lymphocytes. Multidirectional changes in the content of cytokines were revealed: in group I the synthesis of anti-inflammatory cytokines IL-4, IL-10 and in group II – pro-inflammatory IL-1β, INF-γ, TNF-α dominated; in group III the concentration of IL-6 and vascular growth factor (VEGF) was maximally increased. The number of activated CD3+CD4+CD25+ T cells was reduced in groups I and II – by 2.3 and 2.0 times respectively, in group III – increased by 1.2 times. The number of regulatory T lymphocytes CD3+CD4+CD25+CD127neg was reduced by half in I and II groups. Expression of co-stimulatory molecules CD3+CD4+CD28+ was low in all groups and the maximum decrease was in group III. In patients with HCV/HBV, an increase in the expression of the late activation marker of lymphocytes CD3+HLA-DR+ by an average of 63 % was noted. Conclusions. The revealed immune disorders in hepatosplenomegaly of different etiology are characterized by multidirectional changes. Approaches to the treatment of these patients should be complex, taking into account the trigger factors that cause dysregulation of immune responses, which leads to further destruction, and focuses at remodeling target organs.

Inflammatory Choroidal Neovascularisation

Inflammatory choroidal neovascularization is uncommon severe sight threatening complication of uveitis, more frequent in posterior uveitis. Hypoxia, release of vascular endothelial growth factor and other mediators seem to be involved in its pathogenesis. Multimodal imaging including the recent optical coherence tomography angiography greatly aid in diagnosis and management. Management of these neovascular membranes consists of anti-vascular growth factor agents, with or without concomitant anti-inflammatory and/or corticosteroid therapy. Besides effective eradication of inflammation in uveitis, the ideal therapeutic goal should include timely detection and treatment of inflammatory CNVM, as the ultimate visual outcome would depend on the control of both

NEUTRALIZATION OF ANGIOPOIETIN-2 AND VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) FOR THERAPEUTIC PURPOSES

New blood vessels in organs and tissues are formed by angiogenesis, which can take place both in the normal condition and in tumour growth. Angiogenesis supports the strength and integrity of the connections in blood vessel endothelial cells with each other and with the basement membrane. This ensures nutrition of tissues and organs, saturation with oxygen, macronutrients and micronutrients. Along with this, angiogenesis contributes to timely elimination of metabolic products. Metastatic spreading and tumor growth are supported by uncontrolled angiogenesis, that is why it is important to study the works dedicated to neutralization of angiogenesis factors, which becomes a method of combating various oncological diseases and other pathologies. The aim of this work was to study the information about modern drugs, including those at the stage of clinical trials, capable of neutralizing angiopoietin-2 – an inhibitor of angiogenesis and vascular growth factor (VEGF) – an angiogenesis activator, to evaluate the effectiveness and safety of various doses of drugs in various pathologies, to analyze the current state of studying tumor angiogenesis, achievements and prospects for the use of antiangiogenic drugs in oncological practice. The main focus was on the role of angiogenesis inhibitors and activators. To construct and structure the meta-analysis, we conducted a systematic review of the literature, searching works in open Internet resources such as PubMed, CyberLeninka, PsycINFO, Elibrary, published in the period from January 1, 2016 to March 31, 2021, devoted to studies on the effectiveness of drugs aimed at neutralizing angiopoietin-2 and VEGF. Conference materials and dissertations were analyzed to obtain additional data on research in this area.

Topical interferon in recurrent inflammatory macular edema following a cat bite

Introduction: Treating chronic macular edema (CME) post endophthalmitis is a challenge. Use of steroids may reactivate the infection and repeated intravitreal therapy with anti-vascular growth factor inhibitors (Anti-VEGF) puts the patient again at the risk of exacerbation of inflammation or endophthalmitis. We describe a case of CME post traumatic endophthalmitis successfully treated with topical interferon therapy. Case description: A 34-year-old Asian Indian lady with a history of cat bite to her right eye and treated elsewhere as traumatic endophthalmitis with recurrent macular edema, presented to us 1 year after the injury. She had received anti-VEGF injection for same. Her medical history was non-contributory except for close contact with her cat. Therapeutic trials with oral doxycycline followed by oral albendazole with steroids, as well as repeated anti-VEGF therapy failed to prevent recurrence of CME. Patient’s steroid responsiveness and reluctance for injections, made us to opt for a novel topical Interferon therapy. Macular edema resolved in 2 months. Interruption of interferon therapy due to COVID-lock down resulted in recurrence of the CME, which again responded well to interferon monotherapy. Conclusion: Topical interferon may have a role in the treatment of inflammatory macular edema and can serve as a, safer, economical and non-invasive treatment option compared to intravitreal steroids and anti-VEGFs.

Reduced plasma level of basic fibroblast growth factor is associated with incomplete device endothelialization at six months following left atrial appendage closure

Objectives To investigate whether inflammatory and growth factors (IGFs) were associated with incomplete device endothelialization (IDE) at 6 months after successful left atrial appendage closure (LAAC). Background IDE after LAAC is correlated with device-related thrombus (DRT) formation and subsequent thromboembolic events. However, biomarkers for early detection of IDE remain lacking. Methods Plasma levels of IGFs including basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF), stromal cell derived factor (SDF)-1a, transforming growth factor (TGF)-β1, vascular growth factor receptor-1 (VEGF-R1) and von Willebrand factor (vWF) were determined using ELISA kits in 55 consecutive patients with atrial fibrillation (AF) at 6 months after LAAC with Watchman devices. The status of device endothelialization was assessed by transesophageal echocardiography and cardiac CT. Results IDE and complete device endothelialization(CDE)were detected in 38 and 17 patients, respectively. Among the six IGFs, only plasma level of bFGF was significantly lower in patients with IDE compared to those with CDE (303.49 ± 246.84 vs. 556.31 ± 197.84 pg/ml, p < 0.001). C-statistics of plasma bFGF for discriminating patients with IDE from those with CDE was 0.785 (95 % CI: 0.663–0.907, p < 0.001), with a cut-off value of 440.52pg/ml (sensitivity 0.765; specificity 0.789). Multivariate logistic regression model showed that lower bFGF was an independent factor for IDE (OR: 11.752, 95 % CI: 2.869–48.144, P = 0.001). bFGF improved the classification of patients (NRI: 0.677,95 % CI: 0.320–1.033, p = 0.004). Conclusions Reduced plasma bFGF level confers an increased risk for IDE after LAAC. Further prospective studies are warranted to examine if bFGF could serve as a biomarker for IDE post LAAC.

DCE-MRI in Glioma, Infiltration Zone and Healthy Brain to Assess Angiogenesis: A Biopsy Study

Purpose To explore the focal predictability of vascular growth factor expression and neovascularization using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in glioma. Methods 120 brain biopsies were taken in vital tumor, infiltration zone and normal brain tissue of 30 glioma patients: 17 IDH(isocitrate dehydrogenase)-wildtype glioblastoma (GBM), 1 IDH-wildtype astrocytoma °III (together prognostic group 1), 3 IDH-mutated GBM (group 2), 3 anaplastic astrocytomas IDH-mutated (group 3), 4 anaplastic oligodendrogliomas and 2 low-grade oligodendrogliomas (together prognostic group 4). A mixed linear model evaluated the predictabilities of microvessel density (MVD), vascular area ratio (VAR), mean vessel size (MVS), vascular endothelial growth factor and receptors (VEGF-A, VEGFR‑2) and vascular endothelial-protein tyrosine phosphatase (VE-PTP) expression from Tofts model kinetic and model-free curve parameters. Results All kinetic parameters were associated with VEGF‑A (all p < 0.001) expression. Ktrans, kep and ve were associated with VAR (p = 0.006, 0.004 and 0.01, respectively) and MVS (p = 0.0001, 0.02 and 0.003, respectively) but not MVD (p = 0.84, 0.74 and 0.73, respectively). Prognostic groups differed in Ktrans (p = 0.007) and ve (p = 0.004) values measured in the infiltration zone. Despite significant differences of VAR, MVS, VEGF‑A, VEGFR‑2, and VE-PTP in vital tumor tissue and the infiltration zone (p = 0.0001 for all), there was no significant difference between kinetic parameters measured in these zones. Conclusion The DCE-MRI kinetic parameters show correlations with microvascular parameters in vital tissue and also reveal blood-brain barrier abnormalities in the infiltration zones adequate to differentiate glioma prognostic groups.