Urinary tract infection in children: Diagnosis, treatment, imaging - Comparison of current guidelines.

BACKGROUND AND OBJECTIVE: Urinary tract infection (UTI) is a frequent disorder of childhood, yet the proper approach for a child with UTI is still a matter of controversy. The objective of this study was to critically compare current guidelines for the diagnosis and management of UTI in children, in light of new scientific data. METHODS: An analysis was performed of the guidelines from: American Academy of Pediatrics (AAP), National Institute for Health and Care Excellence (NICE), Italian Society of Pediatric Nephrology, Canadian Paediatric Society (CPS), Polish Society of Pediatric Nephrology, and European Association of Urology (EAU)/European Society for Pediatric Urology (ESPU). Separate aspects of the approach for a child with UTI, including diagnosis, treatment and further imaging studies, were compared, with allowance for recent research in each field. CONCLUSIONS: The analyzed guidelines tried to reconcile recent reports about diagnosis, treatment, and further diagnostics in pediatric UTI with prior practices and opinions, and economic capabilities. There was still a lack of sufficient data to formulate coherent, unequivocal guidelines on UTI management in children, with imaging tests remaining the main area of controversy. As a result, the authors formulated their own proposal for UTI management in children.

The effect of tobacco smoke on oxytocin concentrations and selected oxidative stress parameters in plasma during pregnancy and post-partum - an experimental model.

BACKGROUND: Tobacco smoking is a serious threat to life and health of society. Among the most vulnerable to the toxic effects of tobacco smoke are foetuses and newborns. The objective of the research was to assess the impact of tobacco smoke exposure on oxytocin levels and biochemical oxidative stress parameters during pregnancy and after birth in an experimental model. METHODS: In the experiment, exposure to tobacco smoke of gravid and non-gravid rats was monitored. A reliable biomarker of exposure - cotinine - was used in the process and it was determined by means of high-performance liquid chromatography with diode array detection, which ensured high analytical accuracy and precision. Determination of oxytocin was performed by means of enzyme-linked immunosorbent assay. The levels of selected oxidative stress parameters: total protein concentration, uric acid, trolox equivalent antioxidant capacity, protein S-nitrosylation and lipid peroxidation (thiobarbituric acid reactive substances) were measured by spectrophotometric methods. RESULTS AND CONCLUSIONS: The effect of prenatal and postnatal exposure to tobacco smoke was a lower medium body mass of rat foetuses and pups. Oxidative stress during pregnancy, additionally intensified by tobacco smoke exposure, led to adaptive changes in properties of plasmatic antioxidant barriers. Moreover, the disturbance of oxidoreductive balance by tobacco smoke affects oxytocin fluctuations, what was observed in this study during lactation period. Therefore, women who smoke may breastfeed their children less frequently and for a shorter period.

Altered elastase-alpha1-antitrypsin balance in the blood of patients with chronic venous disease.

OBJECTIVES: Although leukocyte elastase is suspected to be involved in the damage of vein wall during chronic venous disease, the equilibrium between this protease and its inhibitor, alpha1-antitrypsin, has not yet been evaluated. The aim of the present study was to determine the relationship between leukocyte elastase and alpha1-antitrypsin, in the blood of patients with chronic venous disease. PATIENTS AND METHODS: The concentration and the activity of leukocyte elastase along with the activity of alpha1-antitrypsin were evaluated in the blood of 55 chronic venous disease patients. The results were compared with those obtained in 33 healthy age and sex-matched volunteers. RESULTS: A significant decrease in the leukocyte elastase activity that correlated with an increased alpha1-antitrypsin activity was observed in the serum of patients with mild clinical symptoms of chronic venous disease. CONCLUSIONS: The results of the study did not confirm a hypothesis about an important role of proteolytic activity of leukocyte elastase in the vein wall injury mechanism. They show that the leukocyte elastase-alpha1-antitrypsin balance is rather shifted toward antiprotease activity, especially in an early stage of chronic venous disease.

Long intronic GAA*TTC repeats induce epigenetic changes and reporter gene silencing in a molecular model of Friedreich ataxia.

Friedreich ataxia (FRDA) is caused by hyperexpansion of GAA*TTC repeats located in the first intron of the FXN gene, which inhibits transcription leading to the deficiency of frataxin. The FXN gene is an excellent target for therapeutic intervention since (i) 98% of patients carry the same type of mutation, (ii) the mutation is intronic, thus leaving the FXN coding sequence unaffected and (iii) heterozygous GAA*TTC expansion carriers with approximately 50% decrease of the frataxin are asymptomatic. The discovery of therapeutic strategies for FRDA is hampered by a lack of appropriate molecular models of the disease. Herein, we present the development of a new cell line as a molecular model of FRDA by inserting 560 GAA*TTC repeats into an intron of a GFP reporter minigene. The GFP_(GAA*TTC)(560) minigene recapitulates the molecular hallmarks of the mutated FXN gene, i.e. inhibition of transcription of the reporter gene, decreased levels of the reporter protein and hypoacetylation and hypermethylation of histones in the vicinity of the repeats. Additionally, selected histone deacetylase inhibitors, known to stimulate the FXN gene expression, increase the expression of the GFP_(GAA*TTC)(560) reporter. This FRDA model can be adapted to high-throughput analyses in a search for new therapeutics for the disease.

Novel BRCA1 mutations and more frequent intron-20 alteration found among 236 women from Western Poland.

Three different novel BRCA1 mutations, five independent cases of the same 12 bp insertion-duplication in intron-20 and two novel rare BRCA1 sequence variants were identified among 122 Polish women with positive, in most cases moderate family history of breast and/or ovarian cancer, 80 controls and 34 unselected breast cancer tissue specimens. All mutations and variants were germline. The 4153 delA frameshift mutation, the Tyr105Cys missense mutation and two cases of the alteration in intron-20 were found in the group of healthy women with positive family history. Two other cases of the intronic insertion were found in unselected controls. Their carriers had no family history of breast or ovarian cancer but other cancers occurred in their families. The 1782 Trp/STOP nonsense mutation and one case of the insertion in intron-20 were first found in tissue specimens of breast cancer patient and breast/ovarian cancer patient, respectively. Their carriers also had no family history of breast or ovarian cancer. The distribution of the insertion in intron-20 in analysed groups and results of RT-PCR experiments suggest a less prominent role for this variant considered earlier a splicing mutation. This study shows also, that more population-oriented research is needed, involving women with less profound or even no family history of breast and ovarian cancer, to better understand the role and significance of different BRCA1 variants and mutations.

CUG repeats present in myotonin kinase RNA form metastable "slippery" hairpins.

We show that CUG repeats form "slippery" hairpins in their natural sequence context of the myotonin kinase gene transcript. This novel type of RNA structure is characterized by strong S1 and T1 nuclease and lead cleavages in the terminal loop and by mild lead cleavages in the hairpin stem. The latter effect indicates a relaxed metastable structure of the stem. (CUG)5 repeats do not form any detectable secondary structure, whereas hairpins of increasing stability are formed by (CUG)11, (CUG)21, and (CUG)49. The potential role of the RNA hairpin structure in the pathogenesis of myotonic dystrophy is discussed.

The value of quantitative bacteriological investigations in the monitoring of treatment of ischaemic ulcerations of lower legs.

The quantitative and qualitative bacteriological investigations of 63 patients were done on ischaemic ulcerations before reconstructive vascular surgery and at 7 day intervals after the operation. Among the isolated bacteria the most common were Gram positive (62.9%), especially Staphylococcus aureus. Amputations due to non-healing ulcers were performed on 8 patients, who had ankle brachial index (ABI) lower than 0.47. In 55 patients with ABI higher than 0.47 (with the exception of one case) free skin grafts were applied to reduce the time of the ulcers healing. Primary healing of ulcers covered with free-skin grafts was achieved in 44 out of 55 patients (80%). In 11 patients, were free-skin grafts had failed, ulcerations were healed following the repetition of the free-skin grafts. The healing results of skin grafts statistically were significantly better in the group where the number of bacteria in 1 cm2 of ulceration was lower than 50.000. The severity of infections in ulcers makes the healing process of skin grafts impossible. Quantitative bacteriology additionally helps in objective evaluation of granulating tissue and facilitates choice of proper skin grafting time. This study has shown the usefulness of quantitative bacteriology for the determination of the severity of infections in ulcers.