[Iron deficiency anemia in a patient with hereditary hemorrhagic telangiectasia. Case report].

Rendu-Osler-Weber disease or hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disease. It is characterized by vascular dysplasia with the formation of telangiectasias on the skin, mucous membranes of the respiratory and digestive tracts, arteriovenous malformations (AVMs) in the internal organs, which is manifested by bleeding. Diagnosis is based on Curacao criteria: recurrent and spontaneous nosebleeds, multiple telangiectases on the characteristic localizations, AVMs in one or more of the internal organs, a family history of HHT (i.e. first-degree relative who meets these same criteria for definite HHT). Therapy is aimed at preventing and stopping gastrointestinal, nosebleeds, correction of iron deficiency anemia. A promising method of therapy is the use of angiogenesis inhibitors, in particular bevacizumab. The article presents a description of a clinical case of HHT in a 49-year-old woman with telangiectisia on the mucous membrane of the tongue, gastrointestinal tract and liver AVMs.

[Erdheim-Chester disease with cardiac involvement. Case report].

ErdheimChester disease (ECD) is a rare non-Langerhans histiocytosis with multisystem inflammatory infiltrates consistent of monocytes/macrophages, reactive microenvironment and fibrotic fields. Cardiovascular involvement is one of the most frequent manifestations of ECD that can lead to life threating complications. In this article we are reporting a clinical case of ECD with cardiac involvement in a young patient.

[Gaucher disease: achievements and prospects].

Gaucher disease (GD) is the most common lysosomal storage disorder, resulting from a deficiency in the activity of a lysosomal enzyme glucocerebrosidase, which is involved in the catabolism of sphingolipids. The phenomenal progress in understanding the pathogenesis and development of specific therapy of this disease over the past 60 years dramatically changed the clinical phenotype of GD, turning a severe progressive disorder into an asymptomatic metabolic defect. The evolution of the understanding of GD associated with fundamental discoveries in the field of cell biology, biochemistry and genetics may be of interest to a wide audience as a model of the effective work of the scientific community in the treatment of rare metabolic pathology.

[Results of phase Ib open multicenter clinical trial of the safety, pharmacokinetics and pharmacodynamics of first biosimilar of eculizumab in untreated patients with paroxysmal nocturnal hemoglobinuria during induction of therapy].

Currently, the main pathogenetic method for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) is the treatment with recombinant monoclonal antibodies that block the C5 component of the complement system. Eculizumab is the first biotechnological drug, which is a monoclonal antibody, with proven clinical efficacy and safety for the treatment of patients with PNH, which is used in world clinical practice. In Russia, in the framework of the state program Development of the pharmaceutical and medical industry for 20132020 was developed Elizaria (JSC GENERIUM) the first biosimilar of the original drug eculizumab. AIM: To evaluate the pharmacokinetic and pharmacodynamic parameters, as well as safety and immunogenicity parameters of the drug Elizara in the induction phase of therapy in previously untreated patients with PNH. MATERIALS AND METHODS: The study included 11 patients with PNH aged 26 to 75 years who had not previously received eculizumab. Each of the study participants was injected with the studied drug Elizaria at a dose of 600 mg intravenously once a week for 4 weeks. RESULTS: During the clinical study, it was noted that the concentration of the studied drug significantly increased by the time the infusion was completed and then gradually decreased to a minimum at the end of the dosing interval. The average concentration of eculizumab 5 minutes before the administration of the study drug at all visits exceeded 35 g/ml, the minimum concentration sufficient to completely inhibit intravascular hemolysis in patients with PNH. The pharmacodynamic efficacy of the drug Elizaria was confirmed by a decrease in the concentration of the membrane-attack complex (MAC) after the first infusion of the drug was maintained at stable levels until visit 5. A persistent decrease in the level of MAC and a four-fold decrease in the average values of lactate dehydrogenase to visit 5 from 1286.4 to 280.9 U/l demonstrated a marked decrease in activity and stabilization of the hemolytic process against the background of the induction of therapy with Elizaria at a dose of 600 mg once a week and confirmed the effecacy of the study drug. Among the 9 adverse events, only 5 had a relationship with the studied drug, including one serious adverse event in the form of an allergic reaction, which, according to the researcher, had a possible cause-effect relationship with the infusion of the studied drug. In 2 patients, low-titer binding anti-drug antibodies were detected without neutralizing activity during treatment with the studied drug, which may indicate its low immunogenicity. CONCLUSION: The study evaluated the pharmacokinetic and pharmacodynamic properties of the drug Elizaria in the regimen of induction therapy in previously untreated patients with PNH, confirming its efficacy. The study demonstrated the safety and low immunogenicity of the study drug.

Geminate recombination in organic photovoltaic blend PCDTBT/PC71BM studied by out-of-phase electron spin echo spectroscopy.

The key process in organic solar cell operation is charge separation under light illumination. Due to the low dielectric constant of organic materials, the Coulomb attraction energy within the interfacial charge-transfer state (CTS) is larger than the thermal energy. Understanding the mechanism of charge separation at the organic donor/acceptor interface still remains a challenge and requires knowledge of the CTS temporal evolution. To address this problem, the CTS in the benchmark photovoltaic blend PCDTBT/PC71BM was studied by the out-of-phase Electron Spin Echo (ESE). The protocol for determining the CTS geminate recombination rate for certain electron-hole distances was developed. Simulating the out-of-phase ESE trace for the CTS in the PCDTBT/PC71BM blend allows precise determination of the electron-hole distance distribution function and its evolution with the increase in the delay after the laser flash. Distances of charge separation up to 6 nm were detected upon thermalization at a temperature of 20 K. Assuming the exponential decay of the recombination rate, the attenuation factor ß = 0.08 Å-1 is estimated for the PCDTBT/PC71BM blend. Such a low attenuation factor is probably caused by a high degree of hole delocalization along the PCDTBT chain.

Differential radiological diagnosis of tuberculous sacroiliitis and bone involvement in Gaucher disease: a clinical case.

Differential diagnosis of bone involvement in patients with Gaucher disease can be challenging. Other diseases with similar radiological signs should be ruled out. Here we present a clinical case of tuberculous sacroiliitis in the patient with type I Gaucher disease. Advanced radiological methods of examination are described. Our case report proves the necessity of an individual approach to the management of such cohort of patients. Keywords: Gaucher disease, tuberculosis of bones and joints, differential diagnosis, comprehensive treatment.

[Enzyme replacement therapy in adult patients with type I Gaucher disease].

Enzyme replacement therapy (ERT) is the standard for the treatment of Gaucher disease (GD). A lifelong intravenous administration of a recombinant analogue of human glucocerebrosidase compensates for the functional deficiency of its own enzyme. The use of ERT has changed the clinical phenotype of GD, a severe progressive disease has been turned into the status of an asymptomatic metabolic defect. At the same time, a reduced dosing ERT regimen applied in Gaucher patients who had achieved therapeutic goals has not yet been developed.

Constrictive pericarditis in a patient with inherited factor VII deficiency.

Constrictive pericarditis (CP) is the final stage of a chronic inflammatory process characterized by fibrous thickening and calcification of the pericardium that impairs diastolic filling, reduces cardiac output, and ultimately leads to heart failure. We present a clinical case of CP in a patient with rare inherited bleeding disorder - factor VII deficiency. Heart failure due to CP was suspected based on clinical symptoms, results of ultrasonic and radiological investigations. The diagnosis was verified by the results of cardiac magnetic resonance imaging. Pericardectomy was performed resulting in significant improvement in the patient's condition.

Management goals for type 1 Gaucher disease: An expert consensus document from the European working group on Gaucher disease.

Gaucher Disease type 1 (GD1) is a lysosomal disorder that affects many systems. Therapy improves the principal manifestations of the condition and, as a consequence, many patients show a modified phenotype which reflects manifestations of their disease that are refractory to treatment. More generally, it is increasingly recognised that information as to how a patient feels and functions [obtained by patient- reported outcome measurements (PROMs)] is critical to any comprehensive evaluation of treatment. A new set of management goals for GD1 in which both trends are reflected is needed. To this end, a modified Delphi procedure among 25 experts was performed. Based on a literature review and with input from patients, 65 potential goals were formulated as statements. Consensus was considered to be reached when ≥75% of the participants agreed to include that specific statement in the management goals. There was agreement on 42 statements. In addition to the traditional goals concerning haematological, visceral and bone manifestations, improvement in quality of life, fatigue and social participation, as well as early detection of long-term complications or associated diseases were included. When applying this set of goals in medical practice, the clinical status of the individual patient should be taken into account.

[Progressive pulmonary hypertension in a patient with type 1 Gaucher disease]. / Progressiruiushchaia legochnaia gipertenziia u patsienta s bolezn'iu Goshe I tipa.

Gaucher disease is the most common form of hereditary enzymopathies combined into a group of lysosomal storage diseases. The basis for the disease is a hereditary deficiency of the activity of acid ß-glucosidase, a lysosomal enzyme involved in the catabolism of lipids, which results in the accumulation of nonutilized cellular metabolism products in the macrophage lysosomes. The main clinical manifestations of type 1 Gaucher disease are cytopenia, hepatomegaly, and splenomegaly, and bone lesion. One of the atypical clinical manifestations of Gaucher disease is damage to the lungs with the development of pulmonary hypertension, which is usually considered within the underlying disease - the development of pneumosclerosis due to macrophage dysfunction. The paper describes a case of progressive pulmonary hypertension in a patient with type 1 Gaucher disease.

Spin dynamics of light-induced charge separation in composites of semiconducting polymers and PC60BM revealed using Q-band pulse EPR.

Light-induced processes in composites of semiconducting polymers and fullerene derivatives have been widely studied due to their usage as active layers of organic solar cells. However the process of charge separation under light illumination - the key process of an organic solar cell is not well understood yet. Here we report a Q-band pulse electron paramagnetic resonance study of composites of the fullerene derivative PC60BM ([6,6]-phenyl-C61-butyric acid methyl ester) with different p-type semiconducting polymers regioregular and regiorandom P3HT (poly(3-hexylthiophene-2,5-diyl), MEH-PPV (poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene]), PCDTBT (poly[N-9'-heptadecanyl-2,7-carbazole-alt-5,5-(4',7'-di-2-thienyl-2',1',3'-benzothiadiazole)]), PTB7 (poly({4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b']dithiophene-2,6-diyl}{3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophenediyl}))), resulting in a detailed description of the in-phase laser flash-induced electron spin echo (ESE) signal. We found that in organic donor-acceptor composites the laser flash simultaneously induces species of two types: a polymer˙+/fullerene˙- spin-correlated polaron pair (SCPP) with an initial singlet spin state and (nearly) free polymer˙+ and fullerene˙- species with non-equilibrium spin polarization. Species of the first type (SCPP) are well-known for polymer/fullerene blends and are usually associated with a charge-separated state. Also, spin polarization of long-living free species (polarons in deep traps) is affected by the laser flash, which is the third contribution to the flash-induced ESE signal. A protocol for extracting the in-phase ESE signal of the SCPP based on the dependence of the microwave nutation frequency on the strength of the spin coupling within the polaron pair was developed. Nutation experiments revealed an unusual pattern of the SCPP in RR-P3HT/PC60BM composites, from which the strength of the exchange interaction between the polymer˙+ and fullerene˙- was extracted. In composites with low-efficient polymers the contribution of the SCPP to the in-phase ESE signal is high, while in composites with high-efficient polymers it is low. This finding can be used as a selection criterion of charge separation efficiency in the polymer/fullerene composites.

[The molecular genetic diagnostic of Gaucher disease type I].

The Gaucher disease is a hereditary enzymopathy underlaid by deficiency of activity of acidic beta-glycosidase, a lysosomal enzyme participating in degradation of products of cell metabolism. The actual study was carried out to characterize genotypes of patients with Gaucher disease in the Russian Federation. The study group consisted of sampling of 122 adult patients with Gaucher disease type I. The technique of allele-specific polymerase chain reaction in real time was applied to screening for detection of four most frequent mutations of gene of acidic beta-glycosidase (N370S, 84GG, L444P, IVS2+ 1). The results of molecular genetic studies demonstrated that in Russian patients the most frequent is mutation N370S and genotype N370S/other mutation. The second allele is presented by mutation not included into number of most frequent mutations of gene of acidic beta-glycosidase.

[Immediate results of combined treatment for soft tissue sarcomas including intraoperative radiation therapy].

Nowadays the most popular and justified, from oncological positions, method of treatment for soft tissue sarcomas is a combined approach with the use of conservative surgery followed by postoperative radiation therapy. In this regard, intraoperative radiation therapy (IORT) in a single dose of 10-20 Gy is a method that optimizes the role of radiation therapy in treatment of this pathology allowing precise localization of radiation zone within the "tumor bed", thereby minimizing damage of normal tissues and critical organs. The aim of the study was to investigate the effect of IORT on the frequency and structure of post-operative complications. Testing group (n = 49) was compared to the group without IORT (n = 57) and group with only surgery (n = 171). According to the study it was not obtained statistically significant differences in the incidence of postoperative complications in the groups (p = 0,57), not marked influence on the structure of post-operative complications.

[Characterization of the genotypes of patients with Gaucher disease type 1 in the Russian Federation].

AIM: To characterize the genotype and genotype-phenotype correlations in patients with Gaucher disease (GD) in the Russian Federation. MATERIALS AND METHODS: One hundred adult patients with GD type 1 were examined. Their clinical study encompassed the evaluation of the severity of osteoarticular lesions from instrumental findings. An allele-specific real-time polymerase chain reaction assay was used to screen four most common acid beta-glucoside gene (GBA) mutations (N370S, 84GG, L444P, IVS2+1). RESULTS: The N370S mutation and the N370S/? genotype where the second allele was presented with the mutation outside the 4 most common GBA gene mutations were found in the Russian patients with GD. Analysis of the clinical manifestations of the disease revealed no association between the genotype under examination and the severity of osteoarticular lesions and supported the unfavorable role of splenectomy (SE) in the development of severe bony disease. CONCLUSION: SE should be carried out in patients with unclear cytopenia and splenomegaly after the diagnosis of GD is excluded. The GD patients undergoing SE should receive emergency enzyme replacement therapy to prevent severe osteoarticular lesions and an irreversible orthopedic defect.

[Tuberculous sacroiliitis in a patient with Gaucher disease].

Gaucher disease (GD) is an inherited enzymatic defect resulting from a deficiency of acid [3-glucosidase, a lysosomal enzyme involved in the degradation of cell metabolic products. The major clinical manifestations of GD are hepatosplenomegaly, cytopenia, and bony involvement varying from asymptomatic osteopenia to severest osteoporosis and ischemic necrosis to develop irreversible orthopedic defects. Timely enzyme replacement therapy with recombinant glucosidase makes it possible to arrest disease progression and to prevent damage to the vital organs. However, GD in adult patients is frequently diagnosed in the presence of occurring osteoarticular lesions (arthrosis deformans, abnormal fractures). In these instances, besides enzyme replacement therapy, high-quality orthopedic care is required. The description of the case history of a patient undergoing splenectomy in childhood is given as a clinical example of severe osteoarticular lesion in GD and complex differential diagnosis with the intercurrent disease extrapulmonary tuberculosis.

[A study of participation of Hdj1 co-chaperone in the modulation of sleep and behavior using micro RNA technology in vivo].

Data obtained for the last 12 years and modern hypotheses on key function of sleep and the role of Heat Shock Protein 70 kDa (HSP70) molecular chaperones family in sleep modulation are insufficient to determine assotiation of sleep quantity to the level of chaperones in the basic "center" of sleep in the ventrolateral preoptic area (VLPA) of the hypothalamus. In the present study, to reduce the content of Hdj1 major co-chaperone of Hsp70 in the VLPA we employed a novel approach based on lentiviral construction containing specific Hdj1-shRNA. The immunoblotting data showed that in 6 weeks after infection the level of Hdj1 in VLPA was reduced by 80% that was accompanied by a considerable increase in the quantity of slow-wave sleep and a marked decrease in the level of anxiety; earlier we found that elevation of Hsp70 level in the rat brain resulted in similar changes. It is suggested that the increase in quantity of slow wave sleep and the decrease in the level of anxiety can be related to a sustained disorder in the integration between molecular systems based on chaperones Hdj1 and Hsp70 and to a compensatory increase in the Hsp70 chaperone activity/level in VLPA.

[Prophylaxis of early radiation injuries to intact tissues following exposure to combined photon-neutron radiotherapy for malignant head and neck tumors].

Our data are presented on comparison of early- and late-response and complications in 320 patients with head and neck tumors after combined photon-neutron radiotherapy (CPNT) alone or in conjunction with cisplatin. Laser therapy via the LGN-222 quartz installation alternating with irradiation sessions was used to prevent and palliate radiation injuries. As a result, the incidence of acute (grade I-II) reactions was significantly lowered and severe fast-neutron-induced complications were avoided. Grade I (RTOG) skin and mucous membrane injuries were rarer in the main group receiving laser therapy (2.47%) as compared with controls (8.93%) (p < or = 0.02). Grade II injuries totaled 11.6% as compared with 5.57% in control (p < or = 0.02). No damage to skin and mucous membranes in grade III-IV (RTOG) was reported. Use of cisplatin was followed by a rise in frequency of both focal (90%) and diffuse (10%) film-coated membrane epithelite (p < or = 0.02). However, radiation-related response was aborted within 10-14 days after treatment in all cases. Our procedure may be used as a method of choice in prophylaxis of severe tissue damage and CPNT-induced complications.

[Role of fast neutrons in the treatment of soft tissue sarcoma].

The report deals with our data on evaluation of combined photon-neutron radiotherapy (CPNT) received by 33 patients with soft tissue sarcoma at the Clinic of the Urals Neutron Therapy Center. Follow-up ranged 10-80 months (median--68 months). Complete response was reported in 100% (control--45%). All the patients survived 12 months after treatment (control--85%); 5-year survival was 42 and 22%, respectively. Our modality appeared to be the only means of ionizing radiation dose dispensation in cases of early relapse after photon therapy when there was a glimmer of hope of stabilization.

[Long-term results of combined photon-neutron radiotherapy for malignant salivary gland tumors at the Ural Neutron Therapy Center].

An evaluation of combined photon-neutron radiotherapy (CPNT) of malignant tumors of the salivary gland (31) is presented. Overall 1-year survival was 100%, 2 years--95%, 3 years--65%, 4 years--57% and 5 years--47%. Radiation-related injury incidence did not vary dramatically: CPNT--15%, photon therapy--11%. Most relapse occurred within the first 24 months.