Jan Schwarz

Synthesis and comparison of photodynamic activity of alkylheteroatom substituted azaphthalocyanines

Abstract Optimal reaction conditions were developed for synthesis of octakis(butylamino), octakis(butylsulfanyl) and octakis(butoxy) azaphthalocyanines (AzaPc’s) with central metal Mg, Zn and metal-free. Their photodynamic activity was measured and compared as a dye-sensitised photooxidation of 1,3-diphenylisobenzofurane (DPBF). Compounds with alkylamino substituent are very poor producers of the singlet oxygen and therefore not suitable as sensitizers for photodynamic therapy (PDT). On the other hand, compounds with alkylsulfanyl and alkoxy substituents possess very good photodynamic activity and are suitable for PDT.

Synthesis and singlet oxygen production of azaphthalocyanines bearing functional derivatives of carboxylic acid

New metal-free, magnesium and zinc azaphthalocyanines (AzaPc) were prepared from 6-(3-tert-butylsulfany1-5,6-dicyanopyrazine-2-ylamino)hexanoic acid and its butylester and N,N-diethylamide. Their singlet oxygen production was measured by a dye-sensitized photooxidation of 1,3-diphenylisobenzofuran (DPBF) and ΦΔ values were calculated. It was found that the presence of carboxylic acid in the structure of AzaPc decreases their singlet oxygen production. Singlet oxygen activity of the newly prepared compounds (containing mixed alkylamino and alkylsulfanyl peripheral substituents) lies between purely alkylsulfanyl and alkylamino derivatives of AzaPc. This fact further supports previously proposed structure-activity relationships, where alkylsulfanyl derivatives belong to the best singlet oxygen producers while the presence of alkylamino substituents in the structure rapidly decreases their photodynamic properties.

Evaluation of faecal calprotectin as a valuable non-invasive marker in distinguishing gut pathogens in young children with acute gastroenteritis

Aim:  The aim of the study is to evaluate faecal calprotectin (f‐CP) in children ≤3 years of age with acute gastroenteritis (AG) as an early predictor of bacterial inflammation.

Gastric emptying of solids in children with H. pylori-positive and H. pylori-negative non-ulcer dyspepsia.

Objective: There is currently no data available in children on possible relationships among Helicobacter pylori, gastric motility and gastric inflammation. This is a prospective study of gastric emptying (GE) in symptomatic children with and without H. pylori who met symptom-based criteria for non-ulcer dyspepsia (NUD). Methods: 47 consecutive dyspeptic patients (23 males; age range, 7 to 18 years) were enrolled. All patients had extensive negative diagnostic investigations. Scintigraphic solid-phase gastric emptying was assessed. Results: 21 H. pylori-positive and 26 H. pylori-negative patients were identified with non-ulcer dyspepsia. The groups were not different in clinical symptoms except that pain related to feeding was more frequent in infected children (P < 0.03). Nodular antral gastritis was found more frequently in the H. pylori positive group (P < 0.0001). The gastritis score was more severe in H. pylori infected than H. pylori negative patients in both fundic and body mucosa (P < 0.001). Within the H. pylori-positive NUD group, the mean half-time GE of a solid meal was significantly accelerated compared to the non-infected group (P < 0.05). There was no difference in the intragastric food distribution and curves of gastric emptying of both groups. A significant relationship was found between the degree of gastric body inflammation gastric emptying, but not antral inflammation. Gastric emptying rate did not differ by sex or age of the subjects in either group. Conclusions: In dyspeptic children with H. pylori, gastric emptying of a solid was significantly accelerated compared with symptomatic H. pylori uninfected patients. This suggests that H. pylori is able to induce gastric emptying acceleration. Our findings add more information on H. pylori infection and gastroduodenal disease.

Helicobacter heilmannii gastroduodenal disease and clinical aspects in children with dyspeptic symptoms

Aim: To evaluate the occurrence and clinical characteristics of Heliobacter heilmannii infection among children presenting with dyspeptic symptoms. Method: Prospective cohort study of 580 patients. Results: Of all examined dyspeptic children, 26.4% were infected with spiral‐shaped organisms, and 0.9% of patients were found to be infected with spiral H. heilmannii‐like organisms.

Paediatric Rome III Criteria-Related Abdominal Pain Is Associated With Helicobacter pylori and Not With Calprotectin.

Objectives: Abdominal pain–related functional gastrointestinal disorders in children include functional dyspepsia, functional abdominal pain, irritable bowel syndrome, and abdominal migraine. We aimed to evaluate a possible association between functional abdominal pain disorders and Helicobacter pylori infection and faecal calprotectin level. Methods: Prospective observational study including consecutive children with functional gastrointestinal disorders fulfilling Rome III criteria (cases) and age/sex-matched healthy controls. H pylori has been detected by biopsy-based tests and stool-antigen detection, faecal calprotectin by enzyme-linked immunosorbent assay. Results: A total of 56 cases (27 with functional dyspepsia) and 56 controls were enrolled. H pylori being detected in 17 of 56 cases (30.4%) and 4 of 56 controls (7.1%, odds ratio: 5.7; 95% confidence interval [CI]: 1.8–18.2, P = 0.003). H pylori was detected significantly more frequently in cases with functional dyspepsia (14/27, 51.9% odds ratio: 14.0; 95% CI: 3.9–49.7, P = 0.00001) than in controls and not in cases with other well-recognized functional gastrointestinal complaints (3/29, 10.3%). The median faecal calprotectin level was similar in cases (7.8 &mgr;g/g, 95% CI: 7.8–8.4) including those with gastritis, and controls (9.1 &mgr;g/g, 95% CI: 7.8–11.3). Gastritis features were more frequent in H pylori–infected and noninfected cases with functional dyspepsia (27/27, 100%) than in cases with other abdominal functional complaints (15/29, 51.7%, P = 0.007). Conclusions: H pylori gastritis and noninfectious gastritis were associated with functional dyspepsia in children referred for abdominal pain–related functional gastrointestinal disorders while faecal calprotectin is not a predictor of gastritis and is similar in children with functional abdominal pain symptoms and in controls.

Inflammatory bowel disease incidence in Czech children: A regional prospective study, 2000-2015

AIM To examine the incidence and trends in pediatric inflammatory bowel diseases (IBDs) over 2000-2015 and project the incidence to 2018. METHODS A 16-year prospective study of IBD patients < 19 years of age was conducted in the Czech Republic (the Pilsen region). All incident IBD cases within a well-defined geographical area were retrieved from a prospectively collected computerized clinical database. Historical Czech data were used for comparison (1990-2001). Our catchment population was determined from the census data. We calculated the incidence by relating the number of newly diagnosed cases to the size of the pediatric population-at-risk in each calendar year. Age/sex, disease type, place of residence, and race/ethnicity were identified. RESULTS In total, 170 new IBD cases [105 Crohn’s disease (CD), 48 ulcerative colitis (UC), and 17 IBD-unclassified (IBD-U)] were identified. The median age at IBD diagnosis was 14.2 years, 59.4% were males, and 97.1% were Caucasians. A male preponderance of IBD (P = 0.026) and CD (P = 0.016) was observed. With 109209 person-years in the catchment area, the average incidence of IBD per 100000 person-years was 10.0 (6.2 for CD, 2.8 for UC, and 1.0 for IBD-U) for children aged 0 to 19 years; for those aged 0 to 15 years, the incidence rate was 7.3 (4.6 for CD, 2.0 for UC, and 0.7 for IBD-U). An increase in incidence with age was observed (P = 0.0003). Over the 16-year period, the incidence increased for IBD patients (P = 0.01) and CD in particular (P < 0.0001), whereas the incidence for UC (P = 0.09) and IBD-U (P = 0.339) remained unchanged. IBD-projected data from 2016 to 2018 were 12.1, 12.3 and 12.6 per 100000 person-years, respectively. CONCLUSION Pediatric-onset IBD incidence is around its highest point. The increase, which is particularly pronounced for CD, may be challenging to relate to causes of pediatric disease.

Current global trends in the incidence of pediatric-onset inflammatory bowel disease

AIM To perform a comprehensive review and provide an up-to-date synopsis of the incidence and trends of inflammatory bowel disease (IBD). METHODS We systematically searched the MEDLINE (source PubMed), EMBASE and Cochrane Library databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (period: 1985-2018) to identify studies reporting population-based data on the incidence of pediatric-onset (< 19 years at diagnosis) IBD in full manuscripts. Two authors carried out screening and data extraction. Choropleth interactive maps and temporal trends were used to illustrate the international differences and incidences of and changes in IBD and subtypes. RESULTS In total, one hundred forty studies reporting data from 38 countries were considered in this review. The highest annual pediatric incidences of IBD were 23/100000 person-years in Europe, 15.2/100000 in North America, and 11.4/100000 in Asia/the Middle East and Oceania. The highest annual incidences of Crohn’s disease (CD) were 13.9/100000 in North America and 12.3/100000 in Europe. The highest annual incidences of ulcerative colitis (UC) were 15.0/100000 in Europe and 10.6/100000 in North America. The highest annual incidences of IBD-unclassified (IBD-U) were 3.6/100000 in Europe and 2.1/100000 in North America. In the time-trend analyses, 67% of CD, 46% of UC and 11% of IBD-U studies reported an increasing incidence (P < 0.05). The risk of IBD is increasing among first-generation of migrant populations. CONCLUSION Globally, the incidence of IBD varies greatly by geographical areas. The steadily increasing incidence of pediatric IBD over time indicates its emergence as a global disease, suggesting that studies should investigate the environmental risk factors among pediatric cohorts.

Advanced SPARQL querying in small molecule databases

BackgroundIn recent years, the Resource Description Framework (RDF) and the SPARQL query language have become more widely used in the area of cheminformatics and bioinformatics databases. These technologies allow better interoperability of various data sources and powerful searching facilities. However, we identified several deficiencies that make usage of such RDF databases restrictive or challenging for common users.ResultsWe extended a SPARQL engine to be able to use special procedures inside SPARQL queries. This allows the user to work with data that cannot be simply precomputed and thus cannot be directly stored in the database. We designed an algorithm that checks a query against data ontology to identify possible user errors. This greatly improves query debugging. We also introduced an approach to visualize retrieved data in a user-friendly way, based on templates describing visualizations of resource classes. To integrate all of our approaches, we developed a simple web application.ConclusionsOur system was implemented successfully, and we demonstrated its usability on the ChEBI database transformed into RDF form. To demonstrate procedure call functions, we employed compound similarity searching based on OrChem. The application is publicly available at https://bioinfo.uochb.cas.cz/projects/chemRDF.Graphical Abstract