Search for neutrinoless double beta decay with enriched 76Ge in Gran Sasso 1990-2003

The results of the HEIDELBERG-MOSCOW experiment which searches with 11 kg of enriched 76Ge for double beta decay in the GRAN Sasso underground laboratory are presented for the full running period August 1990 - May 2003. The duty cycle of the experiment was ~80%, the collected statistics is 71.7 kg y. The background achieved in the energy region of the Q value for double beta decay is 0.11 events/ kg y keV. The two-neutrino accompanied half-life is determined on the basis of more than 100 000 events. The confidence level for the neutrinoless signal has been improved to 4.2 sigma.Comment: 19 pages, latex, 9 figures, 2 table

The use of cytokines in the treatment of cornea inflammatory and dystrophic diseases (review)

Cytokines are unique biologically active substances that form the system of regulation of basic body functions that simultaneously with the nervous and endocrine systems maintain homeostasis under adverse conditions – the introduction of pathogens or violation of the integrity of tissues. Cytokines regulate the amplitude and duration of inflammatory and immune responses, so they are produced and secreted transiently and have a short half-life. These biologically active substances act in very low concentrations. At the same time, the main properties of cytokines are pleiotropy, lack of antigenic specificity, and the ability to form a cascade chain, that allows versatile correction of the spectrum of reparative processes. There are evidences of the possibility of using cytokines in the regeneration of damaged tissues in recent decades. In this connection, a new vector of search for pathogenetically directed ways to improve and restore lost functions using both individual representatives of cytokines and their natural complex is determined. The article reflects the basic information about the influence of cytokines on the development of various diseases of the cornea, as well as the methods of cytokine therapy in the treatment of these pathologies and prospects for their development

Modern etiological and pathogenetic aspects of chronic peripheral uveitis

Intermediate uveitis is among most severe forms of endogenous uveitis which is more common in young people, being characterized by minimal clinical manifestations at early stages of the disorder. A significant and, sometimes, irreversible decrease in visual acuity is associated with development of long-term complications of chronic cintermediate uveitis (CIU), i.e., complicating cataracts (in up to 57% of the cases), cystic maular edema developing at a frequency of up to 31%), as well as ophthalmic hypertension and glaucoma (up to 16% of the patients). The incidence rate of CIU is 1.5 per 100,000 per year. The eye, despite its high immune privilege, is susceptible to infectious and inflammatory diseases. Clinical and histopathological data suggest autoimmune origin of CIU associated with possible response to some endogenous antigen of unknown origin. The main effectors of inflammation in peripheral chorioretinal structures are CD4+T lymphocytes, which are found in paravasal infiltrates and vitreoretinal exudates in CIU. An important role in CIU pathogenesis is attributed to IL-6 and IL-8, TNFá, vascular endothelial growth factor (VEGF), and micro-RNAs, which show increased expression in most CIU patients. Impaired state of intestinal bacterial microbiome is a potential trigger of intraocular inflammation. Genetic predisposition for CIU was also revealed, due to polymorphisms of human leukocyte antigens and some other genes. It is necessary to expand and deepen our knowledge on the disease pathogenesis, in order to develop effective pharmacological treatment of CIU. The article is review of literature discussing the modern scientific ideas concerning etiology and mechanisms of the CIU development

Features of the local cytokine profile of patients with bullous keratopathy by using personalized therapy with cellular technologies

Background. Today we have active development of ophthalmic surgery, but the role of cytokines in the pathogenesis of bullous keratopathy of the cornea remains insufficiently studied at present.The aim. To study the dynamics of the local cytokine profile in bullous keratopathy by using personalized treatment with suspension of autologous blood mononuclears.Material and methods. Two groups of patients with bullous keratopathy were formed: the main group (30 people, 30 eyes), who received an intrastromal injection of a suspension of autologous blood mononuclears and comparison (28 people, 28 eyes), who received a course of pharmacotherapy. The level of interleukins (IL) – IL-10, IL-4, IL-6, IL-1ß, transforming growth factor beta-2 (TGF-β2), tumor necrosis factor alpha (TNF-α) was determined in the lacrimal fluid of the patient’s eye by enzyme immunoassay.Results. All patients before treatment showed an increase of IL-1ß in the lacrimal fluid by 3.3 times, IL-6 – by 4.2 times, TNF-α – by 2.0 times (p < 0.05); an increase in the level of IL-4, IL-10 and TGF-β2 by 1.1 times (p > ˂ 0.05). In the main group, after treatment, there was a decrease in IL-1ß by 2.0 times, IL-6 – by 2.1 times and TNF-α – by 1.8 times, and an increase in IL-10 by 1.5 times, IL-4 – by 1.9 times, TGF-β2 – by 1.4 times (p < 0.05), persisting for 12 months. There was a short-term decrease of IL-1ß by 1.7 times, IL-6 and TNF-α – by 1.2 times and an increase of IL-10, IL-4, TGF-β2 by 1.2 times (p >< 0.05) in the comparison group which then reached the initial values. Conclusion. There is an imbalance in the system of pro- and anti-inflammatory cytokines in bullous keratopathy in the lacrimal fluid. Injection of autologous mononuclear cells in the stroma of the cornea reduces the severity of the imbalance of the local cytokine system compared to the course of pharmacotherapy. Key words: bullous keratopathy, cellular technologies, autologous mononuclear leukocytes, cytokines>˂ 0.05), persisting for 12 months. There was a short-term decrease of IL-1ß by 1.7 times, IL-6 and TNF-α – by 1.2 times and an increase of IL-10, IL-4, TGF-β2 by 1.2 times (p ˂ 0.05) in the comparison group which then reached the initial values.Conclusion. There is an imbalance in the system of pro- and anti-inflammatory cytokines in bullous keratopathy in the lacrimal fluid. Injection of autologous mononuclear cells in the stroma of the cornea reduces the severity of the imbalance of the local cytokine system compared to the course of pharmacotherapy

The formation of eyeball musculoskeletal stump using a Ni-Ti implant in vivo

The purpose of this study is to investigate the possibility of forming an eyeball musculoskeletal stump using a Ni-Ti implant in vivo. Studies were performed on 18 Wistar rats. The animals were enucleated one of eyes. After the enucleation the musculoskeletal stump using Ni-Ti implant was formed. Ni-Ti implant was made from a thread of porous Ni-Ti (TN-10) with a thickness of 100 [mu]m. Before implantation the Ni-Ti implant was sterilized by ethylene oxide. Results showed that the Ni-Ti implant surface was uniform and had not visible defects. The NiTi implant surface was a hydrophobic with the mean value of [theta]=93.5°±1.4. The Ni-Ti implant in the eye orbit was mobile. The Ni-Ti implantation into the eye orbit contributed the connective tissue with blood vessels formation and insignificant leucocytes infiltration (macrophages and lymphocytes infiltration). The study showed the possibility of forming an eyeball musculoskeletal stump using a Ni-Ti implant

Влияние аутологичных мононуклеаров крови на регенераторные процессы при стромальных повреждениях роговицы в эксперименте

In experiment in vivo laws of regeneration of damages of a cornea on background intrastromal introductions of autologus mononuclear blood are studied. It is proved, that local application of mononuclear cells significantly reduces the duration and expressiveness of inflammatory process and as consequence, is accelerated process of regeneration of the damaged corneal tissue.В эксперименте in vivo изучены закономерности регенерации повреждений роговицы на фоне интрастромального введения аутологичных мононуклеаров крови. Показано, что локальное применение мононуклеарных клеток значительно уменьшает продолжительность и выраженность воспалительного процесса и, как следствие, ускоряет процесс регенерации поврежденной роговичной ткани

ЛОКАЛЬНОЕ ПРИМЕНЕНИЕ АУТОЛОГИЧНЫХ МОНОНУКЛЕАРОВ КРОВИ В ЛЕЧЕНИИ ЭНДОТЕЛИАЛЬНО-ЭПИТЕЛИАЛЬНОЙ ДИСТРОФИИ РОГОВИЦЫ

Aim. The article illustrates the way of endothelian – epithepial corneal dystrophy regeneration with intracameral using of authological mononuclear blood cells.Materials and methods. The series of experiments were made on Wistar rats. The main group of animals (12) was done intracameral injection the authological mononuclear blood cells on the posterior corneal surface after corneal dystrophy simulation. The control animals group (12) was made a tradition treatment.The results experiment has shown a high effect of mononuclear cells treatment. The number of dystrophy changed epithelial cells reduced in the main group on the third day after treatment start. The proliferation of endothelian was shown on the seventh day after the treatment in the main group. On the fourteenth day the corneal endothelian was restored in the main animals group. The corneal endothelian layer in the control group hasn’t restored on the twenty first day.Thus, intra cameral injection of authological mononuclear blood cells induces the regeneration of corneal endothelian layer in endothelian – epithepial corneal dystrophy treatment.В работе изучены закономерности развития регенерации при эндотелиально-эпителиальной дистрофии (ЭЭД) роговицы на фоне внутрикамерного применения аутологичных мононуклеаров крови. Цель  исследования – в эксперименте in vivo изучить закономерности развития репаративной регенерации при ЭЭД роговицы на фоне внутрикамерного применения аутологичных мононуклеаров крови. Материал и методы исследования. Выполнена серия экспериментов на крысах-самцах породы Wistar, основной группе (12 особей) которых производили внутрикамерное введение и наслоение аутологичной суспензии мононуклеарных клеток на заднюю поверхность роговицы с предварительно индуцированной ЭЭД. Животные группы сравнения (12 особей) получили традиционное консервативное лечение. Основные Результаты. При анализе результатов лечения ЭЭД роговицы в эксперименте выявлена высокая эффективность внутрикамерного применения аутологичных мононуклеаров крови. Так, на 3-и сут от начала лечения в основной группе количество дистрофически измененных эпителиоцитов сократилось в 15,9 раз от исходного значения, в группе сравнения – лишь в 0,95 раза. Соответственно толщина переднего эпителия роговой оболочки в основной группе уменьшилась в 1,5 раза от первоначального уровня, в группе сравнения – в 0,9 раза. Площадь тканевых щелей в строме роговицы на 3-и сут в основной группе сократилась в 2,2 раза, в группе сравнения – в 1,04 раза. Необходимо отметить, что уже на 14-е сут от начала лечения в основной группе передний эпителий роговицы и его толщина находились в пределах нормы. В группе сравнения данные показатели уменьшились лишь в 1,14 раза и в 1,8 от достигнутого уровня соответственно. Начиная с 7-х сут в основной группе обнаруживались признаки пролиферации эндотелиального слоя роговой оболочки, который к 14-м сут был представлен слоем отростчатых клеток. В группе сравнения эндотелиальный слой роговицы на 21-е сут от начала лечения содержал дистрофически измененные клетки. Заключение .Внутрикамерное введение аутологичных мононуклеаров крови с их наслоением на внутреннюю поверхность роговицы при ЭЭД индуцирует регенерацию эндотелиального слоя, способствуя восстановлению его барьерной функции и уменьшению отека роговой оболочки

Экспериментальное обоснование эффективности «массажа» ретинальных вен для лечения окклюзии вен сетчатки

Objective: evaluate the effectiveness of treatment of retinal vein occlusion with the use of “massage” of retinal veins on the experimental model of photoinduced retinal venous occlusive disease.Materials and methods. Studies were carried out on 30 rabbits of the Chinchilla breed (30 eyes) weighing 1.5–2.0 kg. In the first stage of the experiment, for all animals the photoinduced thrombosis were modeled by laser irradiation of its retinal veins for 0.3–0.4 seconds at a density of 200 J/cm2 and a wavelength of 662 nm after the administration of “Photoditazine” at a dose of 2.5 mg/kg weight. In the second stage of the experiment, the animals were divided into the main group and the comparison group, depending on the method of treatment: 15 animals of the main group with “massage” of the retinal vein in the form of 5–7 movements with a silicone tip of the scanner Tano, 15 animals of the comparison group with epiretinal administration of recombinant prourokinase in a dose 500 international units (IU).Results. The formation of a parietal thrombus in the simulation of photoinduced the central retinal vein occlusion in the experiment leads to a slowing of perfusion in the affected vessel by (8.0 ± 2.5) s (according to fluorescence angiography), an increase in the thickness of the central parts of the retina by (70.2 ± 9.7) μm (according to optical coherence tomography), to the appearance of crimp and uneven lumen of the retina veins, extensive plasma and hemorrhages (according to the data of ophthalmoscopy). On the model of retinal veins thrombosis, a new method of treating retinal vein occlusion was tested, which showed significant efficacy. It has been established that the use of “massage” of the affected retinal vein reduces the time of venous perfusion by 1.3 times and 1.45 times accelerates the resorption of the edema of the central parts of the retina compared to enzymatic thrombolysis.Conclusions. “Massage” of the retinal veins is an effective method of treating retinal vein occlusion and is not accompanied by damage to chorioretinal structures during manipulation.Цель работы: на экспериментальной модели фотоиндуцированного тромбоза центральной вены сетчатки и ее ветвей оценить эффективность лечения окклюзии вен сетчатки с применением «массажа» ретинальных вен.Материалы и методы. Исследование проведено на 30 кроликах породы шиншилла (30 глаз) массой 1,5–2,0 кг. На первом этапе эксперимента всем животным моделировали фотоиндуцированный тромбоз при помощи лазерного облучения ретинальных вен в течение 0,3–0,4 с при плотности воздействия 200 Дж/см2 и длине волны 662 нм после введения фотодитазина в дозе 2,5 мг/кг массы. На втором этапе эксперимента животных разделяли на основную группу и группу сравнения в зависимости от метода лечения: 15 животным основной группы выполняли «массаж» пораженной ретинальной вены в виде 5–7 движений силиконовым наконечником скраппера Tano, 15 животным группы сравнения эпиретинально вводили рекомбинантную проурокиназу в дозе 500 международных единиц (МЕ).Результаты. Формирование пристеночного тромба при моделировании фотоиндуцированной окклюзии ретинальных вен в эксперименте приводит к замедлению перфузии в пораженном сосуде на (8,0 ± 2,5) с (по данным флуоресцентной ангиографии), увеличению толщины центральных отделов сетчатки на (70,2 ± 9,7) мкм (по данным оптической когерентной томографии), появлению извитости и неравномерности просвета вен сетчатки, обширных плазмо- и геморрагий (по данным офтальмоскопии). На модели тромбоза ретинальных вен апробирован новый метод лечения окклюзии вен сетчатки, показавший значительную эффективность. Установлено, что применение «массажа» пораженной ретинальной вены сокращает время венозной перфузии и в 1,45 раза ускоряет резорбцию отека центральных отделов сетчатки по сравнению с ферментным тромболизисом.Выводы. «Массаж» ретинальных вен является эффективным методом лечения окклюзии вен сетчатки и не сопровождается повреждением хориоретинальных структур во время манипуляции