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Резюме УДК 617.735-002-036-08:615.356 ГЗ "Днепропетровская медицинская академия" Украина, 49044, г. Днепропетровск, ул. Дзержинского, 9 State Establishment "Dnepropetrovsk Medical Academy" Dzerzhinsky str., 9 Dnipropetrovsk 49044 Ukraine oko_66@mail.ru Introduction. Diabetic retinopathy - one of the most severe complications of diabetes manifestation of diabetic microangiopathy affecting the blood vessels of the retina of the eyeball, observed in 90% of patients with diabetes mellitus. Most often occurs with prolonged duration of diabetes, but timely eye examination reveals the development of retinopathy in the early stages. Impaired vision - one of the debilitating symptoms of diabetes. Blindness in patients with diabetes mellitus occurs 25 times more likely than those without the condition [2,10,14,15,16,25]. The pathogenesis of diabetic retinopathy is complex. Leading element of microcirculation disorders are related to the structural features of hereditary retinal vascular and metabolic changes that accompany diabetes [1,11,18]. Fluorescence angiography revealed focal capillary occlusion posterior pole, which does not extend to the periphery of the retina. Zone capillary occlusion correlated with symptoms of increased vascular permeability, intraretinalny microvascular problems. The changes are localized mainly paramacular or within the posterior pole [10,12]. It should be noted that until recently, in the pathogenesis of diabetic retinopathy focused glycosylation end products, while the early metabolic disturbances, leading to an accumulation of hydroxyaldehyde and reduced antioxidant capacity, were considered as additional factors in the pathogenesis of this disease. There is significant progress in the study of the molecular basis of diabetes and its ssociated. complications and significantly revealed the role of early glycosylation products [14.18]. It should be pointed out that a very important role in the regulation of tissue metabolism occupy nicotinamide nucleotides: changes in the level of oxidized (NAD - nicotinamide adenine dinucleotide and NADP – nicotinamide adenine dinucleotide phosphate) or the reduced form (NAD• H and NADP • H) can speed up or slow down the oxidation- reduction reactions. The ratio of free forms of oxidized and reduced nicotinamide adenine dinucleotide phosphate (NADP) has a marked influence on the direction and intensity of a number of important catabolic and anabolic processes in the body [8,9,13,17,19,20,24]. Bear in mind that nicotinamide is a non-toxic inhibitor of the nuclear enzyme poly (ADP-ribose) polymerase - PARP, which is activated in diabetes and intensively split over the release of compounds ribose. Last irreversibly damage the nuclear proteins by disrupting the processes of transcription and gene expression. Along with this, violated the energetic processes, reactions glycolytic glucose damage, inhibit the enzyme glyceraldehyde-3-phosphate dehydrogenase, which leads to the activation of protein kinase C and nuclear factor-kB (NF-kB). In addition, significantly stimulated the formation of pro-inflammatory cytokines, such as tumor necrotic factor α Interleukin - 6 and interleukin - 1β and dramatically increases the formation of superoxide radicals [21,22]. Currently being sought new methods of treatment and prevention of the disease, aimed at understanding the key molecular mechanisms of diabetic retinopathy. There is experimental evidence that the simulation application streptozotocin diabetes lipophilic form of vitamin B1 ("Milgamma") and complex amino acids ("Fakovit ") provides. normalizing effect on the metabolism of the retina, which was manifested in the reduction of hydroxyaldehyde and activation of glutathione antioxidant system in the development of experimental streptozotocin diabetes, reduces the elevated levels of the reduced form nicotinamide adenine dinucleotide in the retina and provides stabilization of lysosomal membranes retinal pigment epithelium [5,6,7]. It was found that the inclusion of vitamin B6 in the complex treatment of patients with diabetic retinopathy leads to a significant decrease in the blood concentration hydroxyaldehyde, key elements pathochemical glycosylation processes that damage proteins and membrane structure of the nervous tissue and the vascular endothelium. The use of vitamin B6 in the initial period of experimental diabetes is largely to prevent inhibition of antioxidant systems [3]. The purpose of this study was: to study the clinical efficacy of nicotinamide-containing drugs in patients with initial forms diabetic retinopathy. Material and methods. Studies were performed on 107 patients. Of these, 52 patients(104 eyes) - a comparison group, patients with diabetic retinopathy who received conventional therapy, 55 patients(110 eyes) - study group, patients with diabetic retinopathy and the combined use of cytoflavin and catahrom((cytoflavin injected intravenously in 200 ml of 0.9% Nacl solution for 10 days, then 2 tablets, 2 times a day for 25 days, сatahrom apply 1 drop 3 times a day). Ophthalmologic examination of patients included the study of visual acuity in the tables Golovin - Sivceva, ophthalmoscopy in medical mydriasis using forehead binocular ophthalmoscope. To conduct a comparative analysis on the state of the fundus of patients receiving the observation of patients, and the possibility of aggregation in the works Pavlyuchenko K.P and Oleynik T.V. a scheme for assessment of signs of symptoms point DR. Signs of the DR, which were considered in patients during follow-up were: microaneurysms, microhemorrhages, the presence of hard or soft exudates, intraretinalnye microvascular abnormalities, venous loops, preretinal and retinal hemorrhages, the presence of diabetic maculopathy, retinal edema, neovascularization, fibrous proliferation. Table point evaluation assesses the severity of these signs suggested by the authors listed below. The evaluation of pathological changes in the fundus of patients in the study groups Retina Microaneurysms no 0 has 1-2 fields 1 3-5 fields 2
Hydroxyaldehyde no 0 has 1-2 fields 1 3-5 fields 2 Hard or soft exudates no 0 in a one field 1 more than one field 10 Intraretinal microvascular abnormalities (IRMA) no 0 in 1-3 fields 5 in 3-5 fields 10 Retinal neovascularization no 0 There are 10 Diabetic maculopathy (Any symptoms - edema and hard exudates) no 0 There are 10 Large retinal hemorrhages and preretinal no 0 There are 10 Common retinal edema no 0 There are 10 Venous loop no 0 one field 1 more than one field 5 Beaded venules no 0 there are 10 The study included patients with initial forms of diabetic retinopathy, ophthalmoscopic signs corresponding NPDR scoring table displays retinopathy assigned a minimum score, and the general condition of the fundus estimated by the result on the table. This rating system helps to track the dynamics of the state of diabetic retinopathy and produce its statistical treatment. [4] Results and discussion. The distribution of patients with diabetic retinopathy and control group at the start of observations are shown in Table 1. The initial condition of the patients and control group according to the degree of signs of DR was not statistically significant. From the data table shows that in 78.8% of controls and 76.4% in the study group was manifested in the form of DR microhemorrhages or microaneurysms, with no other changes (assessment had 1-2 points), and 21.2% in the control group and 23.6% in the intervention group had assessment of the retina from 3 to 5 points. The distribution of patients with diabetic retinopathy and control group after 1.5 years of observation are shown in Table 2. As can be seen from the table in the main group of patients remained significantly higher percentage (42.7%) compared with the control group (1%) of the eyes with initial signs of DR as microaneurysms and microhemorrhages, and 95.2% in control and 56. 4% in the study group had assessment of the retina from 3 to 5 points. When comparing the data in terms of monitoring the progression of symptoms 1.5 years in advanced non-proliferative DR and preproliferative stage (up 5 points) in the control group was observed in 3.8% and 0.9% in the core. Data on the comparative assessment of symptom severity of diabetic retinopathy in the study and control groups in the dynamics of observation are presented as the mean scores in Table 3. As can be seen from the data, at the beginning of the observation in the control group of patients point comparative assessment of pathological changes was 1,72 ± 0,80, with the size of the average rank was equal to 108.50. After 1, 5 years in the same group showed a clear increase in pathological changes in the fundus typical for DR. In these conditions, the average score symptom severity of diabetic retinopathy was equal 4,14 ± 0,61, while the comparative rank score was - 140.76. The main group of patients at the beginning of the comparative observation ballroom score was 1,71 ± 0,78, and the average rank - 106.55. After 1.5 years follow-up, there is a modest increase in the severity of pathological changes in the retina. The point Assessment fundus average was 2,91 ± 1,20, while the quantity equal to the average rank - 76.05. The general analysis of the study results severity of clinical signs of diabetic retinopathy based on discrete assessment of pathological changes detected during ophthalmoscopy fundus patients in the control group and the main leads to the conclusion that the use of medication drugs containing nicotinamide, had a clear inhibitory effect on the development of diabetic retinal lesions in patients with early stage disease. Average numerical score ophthalmology revealed pathological changes in the retina of the observation period (1.5 years) in patients treated with nicotinamide products increased by 70.2%, and in patients without medication - by 140.7%. Thus, the data presented by clinical studies and the results of our experimental work on the effect of vitamin B3 on biochemical and biophysical parameters of the retina in animals with streptozotocin diabetes can be considered as justification for the inclusion of nicotinamide containing drugs in complex medical treatment of early forms of diabetic retinopathy. Conclusions: Inclusion in the scheme of medical treatment preparations containing nicotinamide (catahrom and cytoflavin) enabled clearly slow the progression of diabetic retinopathy. In these circumstances, the main group of patients treated with these drugs, the severity of pathological changes in the fundus in 1.5 years was growing to a lesser extent compared with the control group: 1.7 and 2.4 times, respectively. Литература
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