Tumor Suppressors-HTRA Proteases and Interleukin-12-in Pediatric Asthma and Allergic Rhinitis Patients.

Background and objective: Allergy belongs to a group of mast cell-related disorders and is one of the most common diseases of childhood. It was shown that asthma and allergic rhinitis diminish the risk of various cancers, including colon cancer and acute lymphoblastic leukemia. On the other hand, asthma augments the risk of lung cancer and an increased risk of breast cancer in patients with allergy has been observed. Thus, the relation between allergy and cancer is not straightforward and furthermore, its biological mechanism is unknown. The HTRA (high temperature requirement A) proteases promote apoptosis, may function as tumor suppressors and HTRA1 is known to be released by mast cells. Interleukin-12 (Il-12) is an important cytokine that induces antitumor immune responses and is produced mainly by dendritic cells that co-localize with mast cells in superficial organs. Material and methods: In the present study we have assessed with ELISA plasma levels of the HTRA proteins, Il-12, and of the anti-HTRA autoantibodies in children with allergy (40) and in age matched controls (39). Children are a special population, since they usually do not have comorbidities and take not many drugs the processes we want to observe are not influenced by many other factors. Results: We have found a significant increase of HTRA1, 2 and 3, and of the Il-12 levels in the children with atopy (asthma and allergic rhinitis) compared to controls. Conclusion: Our results suggest that the HTRA1-3 and Il-12 levels might be useful in analyzing the pro- and antioncogenic potential in young atopic patients.

The Role of Vitamin D and Vitamin D Receptor Gene Polymorphisms in the Course of Inflammatory Bowel Disease in Children.

Background: The etiopathogenesis of inflammatory bowel disease (IBD) is still unclear. Prior studies suggest genetic components that may influence the incidence and severity of the disease. Additionally, it was shown that low levels of serum vitamin D may have an impact on the clinical course of the disease due to its effect on the immunological system. Methods: We aimed to investigate the correlation between the incidence of vitamin D receptor (VDR) gene polymorphisms (rs11568820, rs10735810, rs1544410, rs7975232, and rs731236, commonly described as Cdx2, FokI, Bsm, ApaI, and TaqI, respectively) and vitamin D concentration with the clinical course of IBD (disease activity, extent of the intestinal lesions). Data were obtained from 62 patients with IBD (34 with Crohn's disease, 28 with ulcerative colitis), aged 3-18 years, and compared with controls (N = 47), aged 8-18 years. Results: Although there was no difference in the incidence of individual genotypes between the study groups (IBD, C) in all the polymorphisms examined, we described a significant increase in the chance of developing IBD for heterozygotes of Cdx2 (OR: 2.3, 95% CI 0.88-6.18, p = 0.04) and BsmI (OR: 2.07, 95% CI 0.89-4.82, p = 0.048) polymorphisms. The mean serum 25OHD level in patients with IBD was significantly higher compared with the controls (19.87 ng/mL vs. 16.07 ng/mL; p = 0.03); however, it was still below optimal (>30 ng/mL). Furthermore, a significant correlation was found between vitamin D level and TaqI in patients with IBD (p = 0.025) and patients with CD (p = 0.03), as well as with the BsmI polymorphism in patients with IBD (p = 0.04) and patients with CD (p = 0.04). A significant correlation was described between the degree of disease activity and genotypes for the FokI polymorphism in patients with UC (p = 0.027) and between the category of endoscopic lesions and genotypes for the Cdx2 polymorphism also in patients with UC (p = 0.046). Conclusions: The results suggest a potential correlation of VDR gene polymorphism with the chance of developing IBD, and the clinical course of the disease requires further studies in larger group of patients. Vitamin D supplementation should be recommended in both children with inflammatory bowel disease and in healthy peers.

The mRNA level of the transforming growth factor ß1 gene, but not the amount of the gene product, can be considered as a potential prognostic parameter in inflammatory bowel diseases in children.

PURPOSE: Transforming growth factor ß1 (TGF-ß1) plays a role in cell proliferation and differentiation, and it can modulate immune response. In this work, we asked whether levels of either TGF-ß1 or mRNA of the corresponding gene in plasma or tissue can be useful in diagnosing and/or monitoring of the clinical course of inflammatory bowel diseases (IBD). METHODS: The study group consisted of 104 pediatric patients with IBD: 36 with Crohn's disease (CD) and 68 with ulcerative colitis (UC); 42 children represented the control group. TGF-ß1 levels in plasma and intestinal mucosa were estimated by ELISA and immunohistochemistry (IHC), respectively. Levels of TGF-ß1 mRNA were determined by reverse transcription and real-time PCR. RESULTS: In patients with IBD, and in subgroups with CD and UC, no significant differences in the TGF-ß1 level in plasma and tissue were found relative to the control group. These variables were not dependent on the stage of the disease, its activity or severity of endoscopic and histopathological findings. TGF-ß1 mRNA levels were significantly higher in tissue samples withdrawn during the relapse of the disease than in those taken during the remission or in the control group. However, no correlation between TGF-ß1 plasma levels and TGF-ß1 mRNA amount in the intestinal mucosa was observed. CONCLUSIONS: The TGF-ß1 mRNA level, but not the amount of the gene product, was significantly increased in the pathologically changed tissue during the relapse of IBD. We suggest that this parameter might be considered as a potential prognostic value when assessing IBD in children.

Diet, Sun, Physical Activity and Vitamin D Status in Children with Inflammatory Bowel Disease.

In the course of inflammatory bowel disease (IBD) malabsorption may lead to a vitamin D deficiency and calcium-phosphate misbalance. However, the reports on the vitamin D status in children with IBD are few and ambiguous. Here, we are presenting complex analyses of multiple factors influencing 25OHD levels in IBD children (N = 62; Crohn's disease n = 34, ulcerative colitis n = 28, mean age 14.4 ± 3.01 years, F/M 23/39) and controls (n = 47, mean age 13.97 ± 2.57, F/M 23/24). Additionally, calcium-phosphate balance parameters and inflammatory markers were obtained. In children with IBD disease, activity and location were defined. Information about therapy, presence of fractures and abdominal surgery were obtained from medical records. All subjects were surveyed on the frequency and extent of exposure to sunlight (forearms, partially legs for at least 30 min a day), physical activity (at least 30 min a day) and diet (3 days diary was analyzed with the program DIETA 5). The mean 25OHD level was higher in IBD patients compared to controls (18.1 ng/mL vs. 15.5 ng/mL; p = 0.03). Only 9.7% of IBD patients and 4.25% of controls had the optimal vitamin D level (30-50 ng/mL). Despite the higher level of 25OHD, young IBD patients showed lower calcium levels in comparison to healthy controls. There was no correlation between the vitamin D level and disease activity or location of gastrointestinal tract lesions. Steroid therapy didn't have much influence on the vitamin D level while vitamin D was supplemented. Regular sun exposure was significantly more common in the control group compared to the IBD group. We found the highest concentration of vitamin D (24.55 ng/mL) with daily sun exposure. There was no significant correlation between the vitamin D level and frequency of physical activity. The analysis of dietary diaries showed low daily intake of vitamin D in both the IBD and the control group (79.63 vs. 85.14 IU/day). Pediatric patients, both IBD and healthy individuals, require regular monitoring of serum vitamin D level and its adequate supplementation.

Two-year follow-up of Sanfilippo Disease patients treated with a genistein-rich isoflavone extract: assessment of effects on cognitive functions and general status of patients.

BACKGROUND: Mucopolysaccharidoses (MPS) are inherited metabolic disorders caused by deficiencies in enzymes involved in degradation of glycosaminoglycans. MPS type III (Sanfilippo disease) is clinically characterized mainly by progressive and severe behavioral disturbances and cognitive dysfunction. Recent 1-year experimental treatment of 10 patients with a genistein (4', 5, 7-trihydroxyisoflavone)-rich extract resulted in improvement of tested parameters, including cognitive and behavioral functions. MATERIAL/METHODS: Eight pediatric patients with Sanfilippo disease were enrolled into the study. The modified version of the Brief Assessment Examination was used to assess cognitive functions. Moreover, 18 different parameters concerning changes in conditions of patients were assessed by their parents. RESULTS: During the first year of the treatment, an improvement of cognitive functions in 7 patients and stabilization in 1 patient were assessed, while after the third year (2-year follow-up) further improvement was observed in 2 patients, stabilization in 3 patients and some deterioration in 3 patients. Monitoring of general and behavioral symptoms revealed improvement in all patients after the first year of the treatment, further improvement in 5 patients, and deterioration in 3 patients during the next 2 years. CONCLUSIONS: We conclude that the treatment of Sanfilippo patients with a genistein-rich soy isoflavone extract (called gene expression-targeted isoflavone therapy [GET IT]) may be effective in either inhibition (in some patients) or slowing down (in other patients) of behavioral and cognitive problems over a longer period. An increased dose of genistein may improve the efficacy of the treatment.

[Reliability of self-reported maternal smoking during early lactation period]. / Ocena wiarygodnosci badan ankietowych dotyczacych palenia tytoniu przez kobiety we wczesnym okresie laktacji.

UNLABELLED: Smoking cigarettes is very common among lactating women. The objective evaluation of an exposure to cigarette smoke is needed, as cotinine concentration. On many research a questionnaire is the only determinant of fact and intensification of smoking. The aim of this research was to establish a reliability of the questionnaire concerning cigarette smoking among lactating mothers by analyzing cotinine/creatinine ratio. MATERIAL AND METHODS: In 51 lactating mothers (participants of the research on oxidative stress in Obstetrics Departments on 3rd day post partum) during check-up visit, on 30th day post partum a questionnaire concerning smoking cigarettes before, during pregnancy and after childbirth, and amount of cigarettes smoked was made. Samples of matutinal urine were deep freezed in - 700 till cotinine was evaluated immunoenzymatically. Women were divided into groups: I of non-smokers (32 women), II of smokers (19 women). Statistical analysis was made by means of unparametric test U Mann-Whitney. RESULTS: Average cotinine/creatinine ratio was 33,8 ng/mg in group I; 1275.9 ng/mg in group II. Specificity and sensitivity of data earned by virtue of statement of correspondents was 81% and 89%. Test of cotinine concentration in urine demonstrated 100% sensitivity and 94% specificity compared to the cotinine/creatinine ratio. Directly proportional relationship was stated between amount of cigarette smoked and concentration of cotinine in urine (55.9 ng/ ml cotinine/cigarette). CONCLUSIONS: A questionnaire should not be the only method evaluating smoking among lactating women. The concentration of cotinine shows slightly lower specificity than cotinine/creatinine ratio. Both tests can be dealt equivalent.

A high-emollient liquid cleanser for very dry and atopic-prone skin: Results of an in-use tolerance and efficacy study conducted under dermatological, pediatric, and ophthalmological supervision.

BACKGROUND: Emollients play a key role in the treatment of eczematous lesions and xerosis such as in atopic dermatitis. However, studies that show the actual benefits of cleansers are few and far between. AIMS: This study aims to evaluate the tolerance and efficacy of a high-emollient liquid cleanser (HELC) designed for very dry and atopic-prone skin, in the absence of any additional skin care. The product is a soap-free and fragrance-free liquid cleanser, containing mild surfactants and a ternary system of selected emollients: glycerin, vaseline, and paraffin. METHODS: In-use study was conducted under dermatological, pediatric, and ophthalmological supervision in 50 subjects (infants, children, and adults) with "dry to very dry and atopic-prone" skin. The primary objective of this monocentric, open, and intra-individual study was to assess the dermatological and ophthalmological tolerance of HELC after 21 days of using it at least once a day on the face and body. The secondary objectives were to evaluate its efficacy based on a clinical score (SCORAD), assess its short- and long-term moisturizing effect by measuring hydration rates (Corneometer® ), and ascertain its cosmetic acceptability through a subjective evaluation questionnaire. RESULTS: The study validates the good dermatological and ophthalmological tolerance of HELC. Its efficacy was demonstrated by improvements in the SCORAD and moisturizing scores. Furthermore, the product was very well accepted by the subjects. CONCLUSION: The fragrance-free HELC tested in this study for 21 days on "dry to very dry and atopic-prone skin" improves skin dryness and pruritus while ensuring good tolerance.

Serum chemerin level, cytokine profile and nutritional status in children with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is characterized by malnutrition and chronic inflammation predominantly occurring in lungs. Evidence suggests a relation between inflammatory activity and nutritional status. Proinflammatory cytokines, playing crucial role in pulmonary destruction in CF, are regarded as a component of the pathogenesis of illness-related malnutrition. Chemerin - a novel marker of a crosstalk between nutrition and inflammation, has not been investigated in children with cystic fibrosis. The aim of this study was to determine serum level of chemerin, interleukin-1b (IL-1b), interleukin-6 (IL-6), tumor necrosing factor α (TNF-α) and interleukin-10 (IL-10) and to verify if they correlate with the nutritional status in children with CF. METHODS: The study included 72 pediatric patients with cystic fibrosis. The control group was comprised of 30 healthy children. Nutritional status parameters: Body Mass Index (BMI), fat mass percentage (FM %) and fat free mass percentage (FFM%) have been assessed in all the subjects basing on bioimpedance and anthropometry according to Slaughter. Serum concentrations of chemerin and cytokines were estimated with ELISA. RESULTS: No statistically significant difference in serum chemerin was found between the studied and the control group. We have documented a significantly higher level of IL-1b, IL-6, TNF-α and IL-10 in CF patients when compared to healthy controls. Neither the chemerin nor the cytokine levels correlated with parameters of nutritional status in our cohort. No statistically significant correlation was found between the serum chemerin and the inflammatory cytokines: IL-1b, IL-6, and TNFα. CONCLUSIONS: Our results show that chemerin is not associated with the nutritional status in children with cystic fibrosis. Chemerin has no impact on the levels of IL-1b, IL-6, TNFα in CF patients. IL-1b, IL6, TNFα and also IL10 are upregulated in cystic fibrosis.

Mast cells in mastocytosis and allergy - Important player in metabolic and immunological homeostasis.

The role of mast cell (MC) activity in pathophysiology is complex and challenging and its clinical effects are difficult to predict. Apart from the known role of MCs in basic immunological processes and allergy, underlined is their importance in bone mineralization and in regulation of autoimmune reactions. Mast cell mediators, especially those released from mast cells in degranulation, but also those released constitutively, are important both in metabolic and immunological processes. Mastocytosis is a heterogeneous group of disorders characterized by accumulation of MC in one or more organs. There are scientific data indicating that mastocytosis patients are at increased risk of osteoporosis in the systemic form of the disease and children with cutaneous mastocytosis have a higher rate of hypogammaglobulinemia. Moreover, the origin of osteoporosis in patients with allergy is no longer considered as linked to steroid therapy only, but to the mast cell mediators' activity as well. There are indications that osteoporosis symptoms in this group of patients may develop independently of the cumulative steroids' dose. Thus, the influence of mast cells on metabolic and immunologic processes in allergic patients should be investigated. The assessment of mast cell activity and burden in mastocytosis may be used to guide clinical management of patients with allergy.

Genistin-rich soy isoflavone extract in substrate reduction therapy for Sanfilippo syndrome: An open-label, pilot study in 10 pediatric patients.

BACKGROUND: Mucopolysaccharidoses (MPSs) are a group of severe metabolic disorders caused by deficiencies in enzymes involved in the degradation of glycosaminoglycans (GAGs)-long chains of sugar carbohydrates in cells that help build bone, cartilage, tendons, corneas, skin, and connective tissue. Although enzyme replacement therapy has become available for the treatment of some types of MPS, effective treatment of neurodegenerative forms of MPS has yet to be determined. Recently, genistein (4',5,7-trihydroxyisoflavone), a specific inhibitor of protein tyrosine kinase, has been found to inhibit GAG synthesis and to reduce GAG concentrations in cultures of fibroblasts of MPS patients. Therefore, a potential substrate reduction therapy has been proposed. OBJECTIVE: The aim of this study was to examine urinary GAG concentration, hair morphology, and cognitive function in patients receiving genistin treatment for Sanfilippo syndrome (MPS type III). METHODS: Patients aged 3 to 14 years with a biochemically confirmed diagnosis of MPS IIIA or MPS IIIB were eligible to enroll in this open-label, pilot study. Genistin-rich soy isoflavone extract 5 mg/kg/d was administered PO for 12 months. Urinary GAG concentration, hair morphology,and cognitive function (measured using a modified version of the Brief Assessment Examination [BAE] and parent observations)were measured at baseline and after 12 months of treatment. RESULTS: Ten patients (6 girls, 4 boys; mean age, 8 years [range,3\2-14 years];mean weight, 28 kg [range, 17\2-43 kg]) were included in the study. All patients had Sanfilippo syndrome; 5 patients had MPS IIIA and 5 had MPS IIIB. After 1 year, statistically significant improvement was found in urinary GAG concentration, hair morphology, and cognitive function. Urinary GAG concentration decreased significantly in all 5 patients with MPS IIIA and in 2 patients with MPS IIIB (P = 0.028). Hair morphology improved significantly in all 5 MPS IIIA patients and in 3 MPS IIIB patients (P = 0.012). A significant increase in the BAE score (by 2-6 points) was noted in 8 patients, while the scores of 2 patients did not change after 12 months of treatment (P = 0.012). No adverse events (AEs) considered related to treatment were reported. Moreover, no AEs not related to the treatment (apart from classical symptoms of MPS III) were noted. CONCLUSIONS: This pilot study found some improvements in GAG concentration, hair morphology, and cognitive function in these pediatric patients with Sanfilippo syndrome treated with genistin-rich soy isoflavone extract for 1 year. Clinical trials are needed to evaluate the efficacy and safety of this potential treatment.

[The analysis of the hepatitis C virus infection course and efficacy of treatment dependence on HLA A antigens in children and youth]. / Analiza zwiazku przebiegu zakazenia wirusem zapalenia watroby typu C oraz skutecznosci leczenia dzieci i mlodziezy z antygenami HLA A.

UNLABELLED: The hepatitis C virus (HCV) infection course and efficacy of treatment may be depended on HLA antigens. The aim of the study is attempt to define dependence between the course of HCV infection and efficacy its treatment and HLA A antigens in children and youth. PATIENTS AND METHODS: To the study included 61 patients (51 after treatment for HCV infection and 10 not treated). The average age was 13.77 years (range 5-18 years). Patients were divided to subgroups in depend on effect of the treatment: virusological and biochemical response. Antigens HLA A were molecularly typed on the low resolution method. To statistical analysis we applied the chi-square test. RESULTS: We demonstrated no statistical significant dependences between HCV infection course and efficacy of its treatment children and youth HLA A antigens. However we observed following tendencies: antigens HLA A *01 and HLA A *02 can be related to unprofitable course of infection and unsuccessful antiviral therapy; HLA A *03 can be favorable prognostic factor for HCV infection course and response to treatment; HLA A *24 can be related to mild course of infection and profitable response to treatment; HLA A *11 can be favorable prognostic factor for course of infection; HLA A *30 can be profitable for efficacy of treatment and HLA A *25 can be disadvantage for it. Probably study performed with larger group of patients could gain dependencies statistical significant. CONCLUSIONS: It is possible that course if HCV infection and efficacy of antiviral treatment are depended on HLA A antigens.

Peripheral regulatory T cells and anti-inflammatory cytokines in children with juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a chronic, heterogenous inflammatory disease of unclear pathogenesis. JIA is hypothesized to be linked to a defective immune regulation. Anti-inflammatory cytokines belong to the best known regulatory factors. T-regulatory cells are a crucial cellular component of immune tolerance. One of their functions is synthesis of interleukin 10 (IL-10) and transforming growth factor beta1 (TGF-ß1). The aim of this study was to determine the proportion of T-regulatory cells (CD4+CD25highFOXP3+) in peripheral blood, and serum levels of TGF-ß1 and IL-10 in patients with JIA. METHODS: The study included 25 patients with newly diagnosed JIA: oligoarthritis (n=17) and polyarthritis (n=8). The control group was comprised of 17 healthy children. CD4+CD25highFOXP3+ T cells in peripheral blood were quantified by means of three-color flow cytometry. Serum concentrations of TGF-ß1 and IL-10 were estimated with ELISA. RESULTS: The proportion of peripheral CD4+CD25highFOXP3+ cells in patients with JIA was significantly higher than in the controls (p=0.04). The two groups did not differ significantly in terms of their TGF-ß1 and IL-10 concentrations. CONCLUSIONS: At the time of diagnosis, children with JIA presented with an elevated proportion of T-regulatory cells (CD4+CD25highFOXP3+) in peripheral blood. Anti-inflammatory cytokines, IL-10 and TGF-ß1, are not upregulated in the serum of patients with JIA, and therefore should not be considered as biomarkers of this condition.

Immune response against HtrA proteases in children with cutaneous mastocytosis.

Mast cells play an important role in both, the innate and adaptive immunity, however, clonal proliferation of abnormal mast cells in various organs leads to mastocytosis. A skin variant of the disease, cutaneous mastocytosis (CM) is the most frequent form of mastocytosis in children. HtrA proteases are modulators of important cellular processes, including cell signaling and apoptosis, and are related to development of several pathologies. The above and the observation that mast cells constitutively release the HtrA1 protein, prompted us to investigate a possible involvement of the HtrA proteins in pediatric CM. Levels of the serum autoantibodies (IgG) against the recombinant HtrA proteins (HtrA1-4) in children with CM (n=36) and in healthy controls (n=62) were assayed. Anti-HtrA IgGs were detected using enzyme linked immunosorbent assay (ELISA) and Western-blotting. In the CM sera, levels of the anti-HtrA1 and anti-HtrA3 autoantibodies were significantly increased when compared to the control group, while the HtrA protein levels were comparable. No significant differences in the anti-HtrA2 IgG level were found; for the anti-HtrA4 IgGs lower levels in CM group were revealed. In healthy children, the IgG levels against the HtrA1, -3 and -4 increased significantly with the age of children; no significant changes were observed for the anti-HtrA2 IgG. Our results suggest involvement of the HtrA1 and HtrA3 proteins in pediatric CM; involvement of the HtrA4 protein is possible but needs to be investigated further. In healthy children, the autoantibody levels against HtrA1, -3 and -4, but not against HtrA2, increase with age.

Association between uridin diphosphate glucuronosylotransferase 1A1 (UGT1A1) gene polymorphism and neonatal hyperbilirubinemia.

OBJECTIVE: To assess the prevalence of UGT1A1*28 and UGT1A1*60 polymorphisms of UGT1A1 gene and their association with hyperbilirubinemia. STUDY DESIGN: The study was performed at a single centre - at the Department of Obstetrics of the Medical University of Gdansk in Poland. DNA was isolated from Guthrie cards of 171 infants. Only full term newborns (gestational age 38-42 weeks) were included in the study. Fluorescent molecular probes were used for UGT1A1 promoter variation analysis. The presence of UGT1A1*28 polymorphism was detected with a dual-probe system, and UGT1A1*60 with a SimpleProbe™. RESULT: Homozygous UGT1A1*28 and UGT1A1*60 genotypes were detected in 14.6% and 20.5% of the newborns, respectively. Homozygous (G/G) genotypes of UGT1A1*60 polymorphism were found in all of the UGT1A1*28 (i.e. (TA)7/(TA)7) homozygotes. More than 80% (55/66) of the children with "wild" type UGT1A1*28 genotype (where no polymorphism was detected) (i.e. (TA)6/(TA)6) carried the "wild" (T/T) genotype of UGT1A1*60 as well. The UGT1A1*28 polymorphism was detected more often among neonates with elevated bilirubin. Hyperbilirubinemia was diagnosed more frequently in boys. CONCLUSION: Polymorphisms of the UGT1A1 gene frequently co-exist in neonates. The presence of UGT1A1*28 polymorphism and male gender seem to predispose to neonatal hyperbilirubinemia.

Lamivudine therapy for children with chronic hepatitis B.

AIM: To assess the effectiveness and side-effects of lamivudine therapy for children with chronic hepatitis B (CHB) who fail to respond to or have contraindications to interferon-alpha (IFN-alpha) therapy. METHODS: Fifty-nine children with CHB were treated with 100 mg lamivudine tablets given orally once daily for 12 mo. Alanine aminotransferase (ALT) activity was evaluated monthly during the therapy and every 3 mo after its discontinuation. HBe antigen, anti-HBe antibodies, HBV DNA level in serum were evaluated at baseline and every six months during and after the lamivudine therapy. Sustained viral response (SVR) to lamivudine therapy was defined as permanent (not shorter than 6 mo after the end of the therapy), namely ALT activity normalization, seroconversion of HBeAg to anti-HBe antibodies, and undetectable viral HBV-DNA in serum (lower than 200 copies per mL). The analysis of the side-effects of the lamivudine treatment was based upon interviews with the patients and their parents using a questionnaire concerning subjective and objective symptoms, clinical examinations, and laboratory tests performed during clinical visits monthly during the therapy, and every 3 mo after the therapy. RESULTS: ALT normalisation occurred in 47 (79.7%) patients between the first and 11(th) mo of treatment (mean 4.4+/-2.95 mo, median 4.0 mo), and in 18 (30.5%) of them after 2 mo of the therapy. There was no correlation between the time of ALT normalization and the children's age, the age of HBV infection, the duration of HBV infection, inflammation activity score (grading), staging, ALT activity before treatment, serum HBV DNA level, and lamivudine dose per kg of body weight. HBeAg/anti HBe seroconversion was achieved in 27.1% of cases. The higher rate of seroconversion was connected with lower serum HBV DNA level and longer duration of HBV infection. There was no connection between HBeAg/anti HBeAb seroconversion and the children's age, age of HBV infection, grading, staging, ALT activity before treatment, and lamivudnie dose per kg of body weight. No complaints or clinical symptoms were observed during lamivudine therapy. Impairment of renal function or myelotoxic effect was noted in none of the patients. CONCLUSION: One year lamivudine therapy for children with chronic hepatitis B is effective and well tolerated. Seroconversion of HBeAg/HBeAb and SVR are connected with lower pre-treatment serum HBV DNA level.

Atypical microbial infections of digestive tract may contribute to diarrhea in mucopolysaccharidosis patients: a MPS I case study.

BACKGROUND: Mucopolysaccharidoses are heritable, metabolic diseases caused by deficiency in an activity of one of specific lysosomal enzymes involved in degradation of mucoplysaccharides (glycosaminoglycans). Among many medical problems of patients with mucopolysaccharidoses, there are frequent episodes of diarrhea of unknown etiology. CASE PRESENTATION: A girl, diagnosed enzymatically for mucopolysaccharidosis type I (deficiency of alpha-L-iduronidase) at the age of 3 years and 9 months, was investigated until the age of 5 years and 4 months. Frequent loose stools and episodes of diarrhea, often accompanied by vomiting, were encountered. Detailed microbiological analyses were performed and atypical microbial infections (most often enetropathogenic Escherichia coli, but also other species, like Pseudomonas aeruginosa or Staphylococcus aureus, as well as adenoviruses) of the digestive tract were found in most severe diarrhea episodes. Often, isolations of pathogenic bacterial strains from stools of the investigated patient suffering from diarrhea were not obvious during the first screening, and only detailed microbiological studies, including re-isolation of colonies, gave the results of isolation of particular pathogenic strains (especially in the case of enetropathogenic E. coli). CONCLUSION: We conclude that atypical microbial infections of digestive tract may contribute significantly to diarrhea in mucopolysaccaridosis patients. Since isolated strains were not typical and their isolation was often possible only after detailed investigation (not during a standard screening), such atypical microbial infections of digestive tract of mucopolysaccharidosis patients could be usually overlooked to date. Importantly, these atypical infections could be effectively treated with antimicrobial agents.

Coexistence of type 1 diabetes mellitus and spinal muscular atrophy in an 8-year-old girl: a case report.

The spinal muscular atrophy is a rare autosomal recessive genetic disease characterized by the progressive loss of muscular strength. In its natural course the disease leads to death. Diabetes mellitus type 1 is an autoimmune metabolic disorder characterized by the disturbed insulin synthesis. This is a case report of an 8-year-old girl suffering from Werdnig Hoffman disease in whom DM1 was diagnosed. The unspecific clinical manifestation and diagnostic difficulties are presented in this paper. To the authors' knowledge, this is the first publication concerning the co-existence of these two medical conditions.

Evaluation of clinical usefulness of serum neopterin determination in children with bacterial infections.

UNLABELLED: Neopterin (NPT) (6-D-erythro-trihydroxypropyl pteridin) is one of the indicators of the immune system activity. Elevated neopterin concentration occurs in diseases mostly involving stimulation of cellular immunity. The determination of neopterin concentration, usually in blood serum and urine but also in many other bodily fluids, has already been applied in many areas of medicine, such as transfusiology, transplantology, oncology, infectious diseases and autoimmunological diseases. OBJECTIVE: The aim of this work is to evaluate clinical usefulness of serum neopterin determination in children with urinary tract infections of confirmed bacterial etiology. MATERIAL: The study involved 56 children with bacterial urinary tract infections - patients of the Clinic of Paediatrics, Paediatric Gastroenterology, Hepatology & Paediatric Nutrition of Medical University of Gdansk in the years 2012-2013. The control group included 105 healthy children. RESULTS: The values of NPT concentration in blood serum obtained in the group of children with urinary tract infections did not significantly differ from the values obtained in the control group. CONCLUSIONS: The determination of neopterin concentration in children with bacterial urinary tract infections is not a clinically useful parameter.

Fecal lactoferrin, a marker of intestinal inflammation in children with inflammatory bowel disease.

The aim of this study was to analyze the usefulness of fecal lactoferrin in the diagnosis and monitoring of inflammatory bowel disease (IBD) in children. The study included 52 children with IBD (24 with Crohn's disease and 28 with ulcerative colitis) aged between 0.92 and 18 years, and 41 IBD-free controls of similar age. Fecal concentration of lactoferrin was determined with a quantitative immunoenzymatic test. Fecal concentration of lactoferrin in children with IBD was significantly higher than in the controls. The cut-off value of fecal lactoferrin concentration optimally distinguishing between the children with IBD and the controls was identified as 13 µg/g. The sensitivity and specificity of this cut-off value equaled 80.7% and 92.7%, respectively, and its positive and negative prognostic values were 96.8% and 63.3%, respectively. Patients diagnosed with moderate Crohn's disease had significantly higher fecal concentrations of lactoferrin than children with the mild or inactive disease. Similarly, children with moderate ulcerative colitis showed significantly higher fecal concentrations of lactoferrin than individuals with the mild condition. No significant relationship was found between the fecal concentration of lactoferrin and the severity of endoscopic lesions. Patients with IBD and a positive result of fecal occult blood test were characterized by significantly higher concentrations of lactoferrin than the individuals with IBD and a negative result of this test. In conclusion, fecal concentration of lactoferrin seems to be a useful parameter for diagnosis and monitoring of IBD in children.

Serum interleukin 6 and interleukin 12 levels in children with chronic hepatitis HBV treated with interferon alpha.

INTRODUCTION: The course of HBV infection and the outcome of interferon alpha (IFNalpha) therapy of patients with chronic hepatitis B, is determined by the antiviral immune response of the host. The aim of the study was to investigate 1) the correlation between IL-6 and IL-12 serum levels and biochemical and histopathological changes in children with chronic hepatitis B, 2) predictive value of pre-treatment serum levels of these cytokines in patients treated with interferon alpha and 3) changes in serum levels of these cytokines after interferon alpha treatment. METHODS: Serum levels of IL-6, IL-12 (heterodimer p70) and IL-12 (heterodimer p70 & p40 subunit) were determined by specific ELISA in 39 children with chronic hepatitis B on the first and the last day of IFNalpha therapy. RESULTS: Serum levels of IL-6, IL-12 (p70) and IL-12 (p70&p40) were respectively within the following ranges of values: 0-1.7 pg/mL, 3.0-85.1pg/mL, 93.7-442.7 pg/mL and they showed no correlation with biochemical and histopathological changes. The pre-treatment cytokines levels in patients who responded and those who did not respond to IFNa therapy did not differ statistically. There was no statistical difference between the end and pre-treatment cytokines levels in both groups. CONCLUSIONS: Serum levels of IL-6 and IL-12 do not reflect the inflammatory activity of hepatitis and have no predictive value of positive response to the IFNalpha therapy in children with chronic hepatitis B. Serum IL-6 and IL-12 levels at the end of INFalpha treatment do not inform of their role in immunological changes which take place while inhibition of HBV replication or virus clearance.