A case of Niemann – Pick disease type C

The paper describes a clinical case of a 27-year-old female patient with Niemann – Pick disease type C (NPC), a rare inherited orphan disease, belonging to a group of lipid storage diseases. It gives an update on the etiology and pathogenesis of this type of glycosphingolipidosis and on established gene mutations. The clinical polymorphism of NPC and the trends in the development of somatic, mental, and neurological disorders are highlighted in relation to the onset age of the disease. The problem of differential diagnosis is discussed. The diagnostic NPC probability index in scores and the latest methods for laboratory diagnostic verification, including molecular genetic testing, are presented.Information is given on specific substrate reduction therapy with miglustat for NPC

Аnalysis of the cytokine profile of blood serum and tumor supernatants in breast cancer

Background. A crucial role in the development of cancer is played by the tumor microenvironment (TM) – a microenvironment that is formed as a result of the interaction between the tumor tissue and macroorganism cells. The concentration of TM cytokines in the blood varies depending on the activity of the tumor and the presence of a metastatic process. It is advisable to study the existing mediator imbalance of TM, its characteristic features in the process of tumor development for the diagnosis and prognosis of the tumor process.The aim. To identify markers of tumor progression in the study of tissue and serum cytokines in women diagnosed with breast cancer.Materials and methods. The object of the study is blood serum cytokines and tumor supernatants (MCP-1, VEGF, TNF-α, IFN-γ, TGF-β1, G-CSF, GM-CSF). The study involved 80 patients with breast cancer aged 50–69 years and 26 practically healthy women aged 41 to 62 years. A standard examination of women was conducted; a cytokine profile study was conducted before the appointment of therapy. To study the cytokine profile at the tissue level, tumor biopsies (n = 30) and biopsies of unchanged breast tissue (n = 6) were incubated to determine the production of MCP-1, VEGF, TNF-α, IFN-γ, TGF-β1, G-CSF, GM-CSF.Results. There was a moderate positive correlation between the stage of the disease and the level of TGF-β1, MCP-1 blood serum, a weak one – with G-CSF. In the incubated tumor tissue, a high positive correlation of cytokines on the stage of the disease is observed in growth factors: VEGF (R = 0.79; p > 0.05) and TGF-β1 (R = 0.61; p > 0.05).Conclusion. The study revealed the characteristic features of the cytokine profile of blood serum and tumor tissue in breast cancer at local and widespread stages. The revealed differences in the level of cytokines should be used as additional diagnostic indicators of the degree of activity and prevalence of the tumor process

Current status of healthcare-associated enteroviral (non-polio) infections

Here we present the data on foreign research publications describing healthcare-associated enteroviral (nonpolio) infections (HAI) sought in the Worldwide Database for Nosocomial Outbreaks (Institut für Hygiene und Umweltmedizin, Universitȁtmedizincomplex “Charite”, Germany) as well as PubMed search engine (The United States National Library), covering 1936–2017 timeframe. The publications retrieved contained the data on 28 nosocomial outbreaks caused by Enterovirus A (EV-A71), В (Echoviruses 11, 17, 18, 30, 31, 33, Coxsackie viruses А9, В2, В5) and D (EV-D68). It was discovered that the majority of the nosocomial enteroviral (non-polio) outbreaks occurred in obstetric hospitals and neonatal units so that children were mainly maternally infected. In addition, a case associated with intrauterine infection was described. It was shown that outbreaks might be started by an infected child at the incubation period. Single publications reported nosocomial outbreaks in geriatric hospitals. Generally, nosocomial enteroviral (non-polio) outbreaks were characterized by polymorphic clinical picture caused by any certain pathogen serotype and within a single site of the infection. Few lethal outcomes were recorded. Enterovirus B species dominated among identified etiological agents. Violated hospital hygiene and infection control contributing to spread of infection were among those found in neonatal units: putting used diapers out on baby bed prior disposal, sharing bathtub, toys and household objects as well as poor hand hygiene in medical workers. One of the measures recommended to improve diagnostics of enteroviral (non-polio) infections was virology screening of children with suspected sepsis in case of unidentified etiology. It was established that etiological decoding of nosocomial outbreaks was impossible without applying pathogen-specific diagnostic tools, mainly nested RT-PCR and direct sequencing of followed by subsequent phylogenetic analysis

Lysosomal acid lipase deficiency – an underestimated cause of hypercholesterolemia in children

Lysosomal acid lipase deficiency (LAL-D) is a rare, progressive, autosomal recessive disease, which develops due to impaired degradation and subsequent intra-lysosomal accumulation of triglycerides and cholesterol esters causing dyslipidemia. The clinical manifestations of the disease presumably depend on the residual activity of the enzyme, lysosomal acid lipase. A profound deficiency of the enzyme known as Wolman’s disease has an onset in the first 6 months of life. The disease reveals itself by dyspeptic disorders in the form of vomiting and diarrhea, lack of weight gain, hepatosplenomegaly, and adrenal calcification. If the Wolman’s disease is not treated, children die within the first 6 months as a result of exhaustion caused by malabsorption syndrome combined with progressive deterioration of liver and adrenal glands. Partial deficiency of lysosomal acid lipase manifests itself at a later age and is called cholesterol ester storage disease. Its clinical presentations include hepatosplenomegaly, elevated transaminases, hypercholesterolemia, and, in some cases, hypertriglyceridemia. Liver failure is the main cause of death in the natural course of cholesterol ester storage disease. Delayed diagnosis of the disease leads to its progression causing irreversible liver damage. The implementation of mass screening programs with the determination of cholesterol levels in childhood is critical to identifying asymptomatic patients.The article presents a clinical case of a patient aged 3 years. The molecular genetic testing showed a mutation in exon 8 of the LIPA gene: NM_000235.3:c.894G>A synonymous variant in the homozygous state. It was also found that both parents of the girl had this type of mutation in the heterozygous state. The patient was prescribed sebelipase alfa in a dose of 1 mg/kg once every 14 days. The treatment was well tolerated. Due to the early verification of the diagnosis and timely pathogenetic therapy, the prognosis of the course of LAL-D, the duration and quality of life of the child were considered to be favourable.Raising the awareness of doctors along with the introduction of effective screening programs for the timely detection of dyslipidemia in children contributes to timely diagnosis and early initiation of pathogenetic therapy, which can increase the life expectancy of patients with lysosomal acid lipase deficiency and improve their quality of life

Assessment of Nutritive Status in Patients with Symptoms of Heart Failure

Aim of the research. To study the parameters of nutritional status of patients with acute and chronic coronary syndromes and symptoms of heart failure in conjunction with clinical, anthropometric, laboratory parameters, structural and functional characteristics of the heart. Materials and methods. A cross-sectional study of 106 patients with acute and chronic coronary syndromes and symptoms of heart failure. All subjects underwent an integrated assessment of the nutritional status (anthropometric, caliperometric (caliper metric) indicators, CONUT scale (lymphocytes, total cholesterol, albumin), hormonal indicators (N-terminal brain natriuretic propeptide), structural changes in the myocardium using echocardiography, exercise tolerance by 6-minute walk test. Results. Nutritional deficiency, according to CONUT scale, was found in 81.1 % of cases (86 patients). In the group of patients with the presence of malnutrition, there were significantly high level of fibrinogen and N-terminal brain natriuretic propeptide. The interpretation of changes in body composition showed a significant upward trend in the prognostic index of hypotrophy and a decrease in lean body mass as heart failure progresses. The dependence of nutritive insufficiency on the CONUT scale with laboratory parameters (creatinine, fibrinogen, brain natriuretic propeptide), structural and functional characteristics of the heart (diastolic and systolic dimensions of the left ventricle, ejection fraction, left ventricular myocardial mass index), a functional indicator of tolerance to the physical load (6-minute walk test) was determined. Conclusion. An integrated analysis of nutritional status indicators of patients with heart failure revealed an increase of malnutrition signs with an increase of the severity of HF. Pathological effects of nutritional deficiency are associated with impaired left ventricular systolic function, reduced exercise tolerance

Comorbidity of tics and epilepsy in children and adolescents

Tics are the most common forms of hyperkinesis among children and adolescents, the etiology of which is not fully clear. A study has shown a high comorbidity of tic disorders and epilepsy, as evidenced by video-EEG monitoring. In patients with tics even in the absence of epileptic seizures, epileptiform activity is an adverse predictor and a determinant of the potential risk of comorbid epilepsy especially during neuroleptic therapy. Antiepileptic drugs are the drugs of choice to treat this category of patients

Treadmill training effect on the myokines content in skeletal muscles of mice with a metabolic disorder model

The effect of treadmill training loads on the content of cytokines in mice skeletal muscles with metabolic disorders induced by a 16 week high fat diet (HFD) was studied. The study included accounting the age and biorhythmological aspects. In the experiment, mice were used at the age of 4 and 32 weeks, by the end of the experiment—respectively 20 and 48 weeks. HFD feeding lasted 16 weeks. Treadmill training were carried out for last 4 weeks six times a week, the duration 60 min and the speed from 15 to 18 m/min. Three modes of loading were applied. The first subgroup was subjected to stress in the morning hours (light phase); the second subgroup was subjected to stress in the evening hours (dark phase); the third subgroup was subjected to loads in the shift mode (the first- and third-weeks treadmill training was used in the morning hours, the second and fourth treadmill training was used in the evening hours). In 20-weekold animals, the exercise effect does not depend on the training regime, however, in 48-week-old animals, the decrease in body weight in mice with the shift training regime was more profound. HFD affected muscle myokine levels. The content of all myokines, except for LIF, decreased, while the concentration of CLCX1 decreased only in young animals in response to HFD. The treadmill training caused multidirectional changes in the concentration of myokines in muscle tissue. The IL-6 content changed most profoundly. These changes were observed in all groups of animals. The changes depended to the greatest extent on the training time scheme. The effect of physical activity on the content of IL-15 in the skeletal muscle tissue was observed mostly in 48-week-old mice. In 20-week-old animals, physical activity led to an increase in the concentration of LIF in muscle tissue when applied under the training during the dark phase or shift training scheme. In the HFD group, this effect was significantly more pronounced. The content of CXCL1 did not change with the use of treadmill training in almost all groups of animals. Physical activity, introduced considering circadian rhythms, is a promising way of influencing metabolic processes both at the cellular and systemic levels, which is important for the search for new ways of correcting metabolic disorders

Болезнь Помпе с поздним началом c фенотипом поясно-конечностной миодистрофии

Pompe disease, also known as type II glycogenosis, is a rare autosomal recessive disease. Two main types include early-onset Pompe disease – severe, rapidly progressive multisystem deficency, manifestating on the first year of life, and late-onset Pompe disease (LOPD), with the age of onset ranging from the first year till late adulthood. Both types are caused by the deficiency of lysosomal acid-α-glucosidase due to the mutations in GAA gene, leading to an excessive storage of glycogen in body cells. LOPD is a slowly progressive disease with a primary lesion of a skeletal, respiratory and cardiac muscles, affected in different grade, and moderately elevated сreatine kinase. It is often difficult to perform differential diagnosis with a large group of hereditary and non-hereditary myopathies. We present a case report of LOPD with signs of limb-girdle muscular dystrophy.Болезнь Помпе (БП) или гликогеноз 2-го типа – редкое аутосомно-рецессивное заболевание. Выделяют 2 основные формы БП – младенческую, с дебютом в первый год жизни, и БП с поздним началом (БППН), с дебютом в любом возрасте после первого года жизни. В основе обеих форм лежат одинаковые генетический и патофизиологический механизмы развития, проявляющиеся мутацией гена GAA и снижением активности фермента кислой-α-глюкозидазы, в результате чего в клетках тканей организма накапливается гликоген. Клинически БППН характеризуется вариабельностью поражения скелетной и дыхательной мускулатуры и в отличие от тяжелой, быстро прогрессирующей полиорганной патологии при младенческой форме, может сочетаться лишь с минимальными поражениями сердца и других органов. Фенотипический полиморфизм, незначительное повышение креатинкиназы вызывают затруднения в дифференциальной диагностике БППН и большой группы наследственных и ненаследственных миопатий. Представлен случай диагностики и дифференциальной диагностики БППН с фенотипом поясно-конечностной миодистрофии