[The effectiveness of a probiotic containing Bifidobacterium longum BB-46 and Enterococcus faecium ENCfa-68 in the treatment of post-infectious irritable bowel syndrome. Prospective randomized comparative study].

BACKGROUND: In the treatment of post-infectious irritable bowel syndrome (PI-IBS), the leading role belongs to the normalization of the composition of the intestinal microbiome, the disturbances of which are associated with previous intestinal infections. AIM: To study the effectiveness of the drug Bifiform in the treatment of PI-IBS. MATERIALS AND METHODS: An open, prospective, comparative, randomized study included 62 patients with PI-IBS. The diagnosis was confirmed by the results of clinical, laboratory and endoscopic examination of the intestine and met the diagnostic criteria for IBS of the Rome Consensus IV. The patients were randomized into 2 groups depending on the therapy. The patients of the main group received an antispasmodic drug (mebeverin 200 mg 2 times a day or trimebutin 200 mg 3 times a day for 4 weeks), an antibiotic (rifaximin 400 mg 3 times a day or nifuroxazide 400 mg 2 once a day for 1 week), a drug that normalizes the consistency of feces (dioctahedral smectite or macrogol 4000) and Bifiform 2 capsules 2 times a day for 2 weeks. For patients of control group similar therapy was performed without the Bifiform. Evaluation of the effectiveness of treatment was carried out at the end of the course of therapy and 6 months after its termination. RESULTS: All included patients with PI-IBS had abdominal pain, flatulence and tenderness to palpation along the bowel, most of them had diarrhea. Disorders of the intestinal microbiota were detected in 77.4% of patients, while excessive bacterial growth in the small intestine occurred in 72.6%, disorders of the colon microbiocenosis with the presence of opportunistic bacteria in 62.9% of patients. A significant part of the patients had a combination of small and large intestinal dysbiosis. Histological examination of the colon mucosa showed signs of low degree of inflammation activity in all patients. The moderate increase in the level of fecal calprotectin was found in 62.2% of patients with colonic dysbiosis. The majority of patients in the main group showed a pronounced positive dynamics of clinical manifestations of the disease, restoration of the normal composition of the intestinal microbiota and normalization of the content of fecal calprotectin at the end of the course therapy. The good result was observed much more often in the main group at the end of the course of treatment and 6 months after its termination. CONCLUSION: The inclusion of Bifiform in the complex therapy of PI-IBS significantly increases its effectiveness both in arresting the clinical manifestations of the disease, and in restoring the normal composition of the intestinal microbiome and reducing the inflammatory process in the intestinal mucosa. In the majority of patients receiving Bifiform, the remission of the disease achieved at the end of the course of treatment and persisted even 6 months after its termination.

[A prospective randomized comparative study of the efficacy and safety of a two-week bismuth-based quadrotherapy of Helicobacter pylori infection with the inclusion of the probiotic containing Bifidobacterium longum BB-46 and Enterococcus faecium ENCfa-68 ].

AIM: To study the efficacy and safety of a two-week bismuth-based quadruple of Helicobacter pylori (Hp) infection with the inclusion of a probiotic Bifiform. MATERIALS AND METHODS: An open prospective comparative randomized study included 68 Hp-positive patients: 22 with a confirmed diagnosis of peptic ulcer disease, 46 with chronic gastritis, gastroduodenitis and erosions in the pylorobulbar zone. The diagnosis and Hp infection were verified by the results of endoscopic and morphological studies, as well as using the 13C-urease breath test and determination of the Hp antigen in the feces. Depending on the therapy, the patients were randomized into 2 groups: the main group was taken 2 times a day for 14 days omeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg + bismuth tripotassium dicitrate 240 mg + Bifiform 2 capsules 2 times a day; control similar therapy was carried out, but without the inclusion of Bifiform. Repeated testing for Нр was carried out one month after the termination of the course of treatment. RESULTS: When using bismuth-containing quadruple, a high frequency of Hp eradication was noted, which in the ITT analysis was 86.1 and 68.8% (p0.05) and in the PP analysis it was 93.9 and 95.7% (p0.05) in patients of the main and control groups, respectively. Side effects of drug therapy were detected in 16.7 and 43.8% (p0.05), which was the reason for the early termination of therapy as a result of their development in 5.6 and 28% (p0.05) in patients of the main and control groups, respectively. The inclusion of the probiotic Bifiform in the eradication triple therapy of Hp infection reduced the frequency of detection of colonic dysbiosis from 27.8 to 3.6% and had a positive effect on the indices of local immunity (increased content of plasma cells in the inflammatory infiltrate and a stable level of secretory immunoglobulin A in coprofiltrate). CONCLUSION: A prospective, comparative, randomized study has shown that when using a two-week bismuth-based quadruple the eradication rate exceeds 90%. The inclusion of Bifiform in the eradication scheme dramatically reduces the frequency of adverse events and increases patient compliance, and also maintains the protective factors of the gastrointestinal mucosa at a higher level.

[Nutrition and orphan diseases].

Diagnosis and treatment of orphan (rare) diseases is an important problem of modern pediatrics due to multivarious clinical signs and severe course of this pathology. Orphan diseases are associated with accumulation, absence or insufficient synthesis of one or several metabolites in the organism. The absence of early diagnostics and treatment of patients with such diseases leads to bad prognosis. A diet is the main treatment method of many orphan diseases. A diet must be personalized and base on thorough examination of nutritional status. Individual diet therapy promotes an improvement of patient`s status and enhances an effect of other forms of treatment for compensation of metabolic disorders, decrease of complication risk and increase of life quality. The article summarizes the experience of treatment of children with orphan diseases in the Department of Pediatric Gastroenterology, Hepatology and Nutrition of Federal Research Centre for Nutrition, Biotechnology and Food Safety. 444 patients with inherited disorders of carbohydrate metabolism, lipid metabolism and more rare diseases (tyrosinemia, lysosomal acid lipase deficit, fructosemia, urea cycle disturbances, α1-antitrypsine insufficiency etc.) have been evaluated in the Department since 2008. The results of the examination and treatment of children with glycogen storage diseases (n=131), fructosemia (n=18), inherited disturbances of lipid metabolism (n=118) and other rare diseases are represented in the paper. The monitoring of nutritional status can help to correct therapy depending on character and severity of pathological process for benign course of the disease.

[Biomarkers of vitamin status in obese school children].

Inadequate intake of vitamins, noted in children with obesity, reduces the immune system activity, contributes to the metabolic disorders aggravation and may result in comorbidity. The aim of the work was to study sufficiency with vitamins and carotenoids of children with obesity. Material and methods. Examination of vitamin D, B2, C, A, E and ß-carotene status in 50 children (male 36.0%) aged 11-17 years [median (Me) - 14 years] with obesity [Z-score body mass index (BMI) >=2.0, Ме=2.86] by determining serum biomarkers has been conducted. Results and discussion. All of the children had an adequate supply with vitamin C (ascorbic acid level >0.4 mg/dL). Low vitamin A status (retinol <30 µg/dl) was revealed in 8% children. Deficiency of vitamin D [25(OH)D<20 ng/ml], vitamin B2 (riboflavin <5 ng/ml) and ß-carotene (<10 µg/dl) was detected in 62.0, 38.8 and 74.0% of obese children. The percentage of persons with reduced vitamin E serum level (<0.8 mg/dl) was amounted 54.0%. A severe vitamin D deficit (<10 ng/ml) has been detected in 24.0% of children with Z-score BMI >=2.86 (median value) and has not been observed in children with lower body weight, whose serum ß-carotene median was 1.5 fold higher (p<0.05). No one was adequately supplied with all 5 studied vitamins and ß-carotene. The combined deficiency of 3 or more vitamins took place in 54.0% of obese children. Synchronously suboptimal serum level of ascorbic acid (<50 µmol/l), ß-carotene (<0.4 µmol/l) and α-tocopherol/cholesterol ratio (<5.0 µmol/mmol) which is a cardiovascular disease risk factor, has been found in 28.0% of children. BMI was inversely associated with 25(OH)D serum concentration (ρ=-0.313, р=0.027). There was a pronounced negative correlation between serum level of ß-carotene and atherogenic LDL cholesterol (ρ=-0.514, p<0.001). Conclusion. The prevalence of combined vitamin D, tocopherol and carotenoids' inadequacy in obese children indicates the importance of vitamin status correction to reduce the risk of metabolic syndrome.

The novel synonymous variant in LIPA gene affects splicing and causes lysosomal acid lipase deficiency.

Lysosomal acid lipase deficiency (LALD; MIM#278000) is a continuum of autosomal recessive diseases caused by defects in the gene LIPA and historically divided into two phenotypes: severe infantile-onset form called Wolman disease (WD) and childhood/adult-onset form known as cholesteryl ester storage disease (CESD). We report a novel synonymous homozygous variant c.600G > A in LIPA of a patient with LALD. Functional analysis of the patient cDNA and minigene assay revealed this variant as the cause of exonic cryptic splice site activation and 63 b.p. deletion in exon 6. To investigate the impact of this in-frame deletion on protein function, we performed 3D modeling of the human lysosomal acid lipase and showed the alteration of highly conservative region in close proximity to protein active site, which may completely eliminate the enzymatic activity. Using transcript specific real-time quantitative PCR method, we evaluated the relative ratio of the patient's wild type transcript isoform which is significantly reduced and correlates with severe childhood-onset variant of LALD.

[The third case report a patient with primary aldosteronism, seizures, and neurologic abnormalities (PASNA) syndrome de novo variant mutations in the CACNA1D gene]. / Tretii sluchai sindroma pervichnogo al'dosteronizma, sudorog i nevrologicheskikh narushenii (PASNA), obuslovlennogo variantom mutatsii de novo v gene CACNA1D.

Germline mutations in CACNA1D cause the primary aldosteronism, seizures, and neurologic abnormalities (PASNA) syndrome (OMIM# 615474) characterized by primary aldosteronism, seizures and neurological abnormalities. The authors present a case-report of a 1-year 3-month male patient with neurological symptoms such as seizures and global developmental delay with primary hyperaldosteronism. The heterozygosis disease-causing variant c.776T>A in CACNA1D gene was identified.

[Characteristics of lipid metabolism and the cardiovascular system in glycogenosis types I and III]. / Kharakteristika lipidnogo obmena i sostoianie serdechno-sosudistoi sistemy pri glikogenozakh I i III tipov.

Glycogen storage disease (GSD) is an inherited metabolic disorder characterized by early childhood lipid metabolic disturbances with potentially proatherogenic effects. The review outlines the characteristics of impaired lipid composition and other changes in the cardiovascular system in GSD types I and III. It analyzes the factors enabling and inhibiting the development of atherosclerosis in patients with GSD. The review describes the paradox of vascular resistance to the development of early atherosclerosis despite the proatherogenic composition of lipids in the patients of this group.

[THE CLINICAL COURSE OF HEPATITIS C IN CHILDREN WITH DIFFERENT VARIANTS OF THE GENE POLYMORPHISM IL28B].

Aim of investigation: The aim of the research is to study the clinical course of hepatitis C in children with different variants of the gene polymorphism of IL-28B. Materials and methods: We observed 94 children (46 girls and 48 boys) with chronic hepatitis C (CHC) in age from 3 to 17 years (mean age 10 years). There were significant differences in the distribution of allele frequencies in children with chronic hepatitis C and in the population. In children with chronic hepatitis C significantly increased the incidence of the T allele at the locus of the gene IL-28B rs12979860 C>T, which makes it possible to consider it as a predictor of antiviral therapy ineffective. Results: When analyzing the frequency of occurrence of a polymorphic variant T>G [rs8099917] IL-28B gene in children with chronic hepatitis C and healthy children revealed no differences in the distribution of alleles. Conclusion: Personalized approach to the appointment of HCV antiviral therapy in children is to carry out genetic studies to determine on the basis of predictive features of the course of HCV in children during the treatment.

[Age-dependent characteristics of nutritional status and resting metabolism in overweight and obese children].

The age-dependent nutritional status and resting metabolism in overweight and obese children have been examined. The study included 625 children of 2.5-17 years old. Patients were divided into three groups: 1st--2.5-7 years old (n = 49), 2nd--8-12 years old (n = 204), 3rd--13-17 years old (n = 372). The diagnosis of overweight and obesity was based on CDC criteria: children with 85-94 BMI percentile according to age and gender had overweight, BMI 295 percentile--obesity. Anthropometry, bioelectric impedance analysis and indirect respiratory calorimetry were performed; lipid and carbohydrate parameters were measured. The fat mass percentages in children of studed groups were 41.3 ± 1.9, 39.8 ± 0.7 and 42.3 ± 0.4%, the mean percent of fat mass excess--163.6 ± 26.2, 113.7 ± 8.3 and 134.9 ± 8.2% respectively, p > 0.05. Prevalence of dyslipidemia in children increased with age: lipid metabolism disorders were revealed in 28.6, 49.0 u 53.2% children of the 1st, 2nd and 3rd groups respectively. The mean HDL level in the 1st and 2nd groups was significantly higher, and triglycerides--lower than in the 3rd group. The correlation of HDL level and breastfeeding duration (r1 = 0.94, p < 0.05) was found in the 1st group of children. Increased insulin level was revealed in 38.8% children in the 1st group (mean 12.8 ± 1.4 µIU/ml), 62.2% children in the 2nd group (21.1 ± 0.7 µIU/ml) and 64.8% children in the 3rd group (25.1 ± 0.9 µIU/ml); increased HOMA--in 36.7% (4.32 ± 0.6), 62.2% (4.65 ± 0.17) and 59.1% (5.56 ± 0.21) respectively. The negative correlation of insulin and HOMA level with breastfeeding duration (r1 = -0.38 and -0.37, respectively, p < 0.05) was found in the 1st group of children. Prevalence of hyperuricemia increased from 13% in the 1st group to 21.1% in the 2nd and 44.1% in the 3rd group. Prevalence and degree of resting metabolism changes increased with age and had tendency to the shift of proportion of energy-intensive substrates (fats and carbohydrates) to deceleration of carbohydrate oxidation (in 32, 50, 55.1% of children) and compensatory fat oxidation acceleration (8, 28.4 and 34.7% respectively). Mean fat oxidation rate levels significantly differed between groups and increased with age (48.38 ± 7.14, 54.29 ± 3.06 and 78.43 ± 2.89 g/day in children of the 1st, 2nd and 3rd groups respectively, p < 0.001). The mean level of carbohydrate oxidation rate in the 3rd group of children was lower than normal value (p < 0.01). Resting energy expenditure was lower in the 2nd and 3rd groups of children.

[The natural course of chronic HBV+HCV infection in children].

At the present time there is a growth in the number of children suffering from chronic viral hepatitis (CVH). The most difficult group consists of patients with mixed-hepatitis, which is associated with a more rapid progression of the disease and the formation of cirrhosis of the liver. The paper presents the data of long-term monitoring of children with chronic hepatitis B+C (CH B+C); it demonstrates the features of a clinical course, the nature of the biochemical, immunologic, and morphologic changes in the natural course of the disease.

[A case report of Byler's syndrome].

The case report describes a progressive familial intrahepatic cholestasis II type Byler's syndrome with structural abnormality of the bile canalicular membrane. A child with a rare hereditary pathology,who is on the waiting list for liver transplantation, on the background of complex treatment, including diet therapy, drug therapy achieved a positive dynamics of clinical and laboratory parameters, acceleration of physical, psychomotor and intellectual development, that in general has improved the surgery prognosis and quality of life of the patient.

[Functional performance of the cardiovascular system in patients with overweight and obesity].

Was investigated 471 patients with obesity and cardiovascular diseases. Direct dependence between degree of expressiveness of obesity and the clinical status, severity of infringement of a functional condition of cardiovascular system, frequency of development of complications is revealed.

[Dietotherapy children with liver diseases].

In children with liver diseases disorders of the nutritional status appear more quickly and delay normal growth and development. Administration of the nutritional support based on nosological and syndromal approaches lets provide optimal conditions for normalization of the liver functions, improves efficiency of therapy and prognosis of the disease. The article contents modern recommendations on the organization of nutrition in children with different liver diseases, correction of metabolic disorders during complications of liver pathology.