The role of botulinum toxin in the management of nonneurogenic overactive bladder in children: Highlights for clinical practice. A systematic review.

Overactive bladder (OAB) is the most common voiding dysfunction in children; however, nonneurogenic or idiopathic OAB remains poorly studied. First-line treatment includes conservative measures; however, as many patients are refractory, have adverse effects, or are contraindicated for anticholinergics, new options must be explored. This review covers the use of intravesical botulinum toxin (BoNT) for idiopathic OAB treatment in children, emphasizing its efficacy, safety, differences between toxins, doses, and injection techniques. Clinical results were promising, with all 8 studies reporting good results. All authors used BoNT type A (BoNT-A), either onabotulinum or abobotulinum toxin A. Response rates were variable, with full-response percentages of 32%-60%. As proven by the full-response rates of 50%, repeated injections are as safe and effective as first injections. Only a few cases of urinary tract infection, transient urinary retention, and hematuria have been reported, with no major local or systemic adverse effects. Despite these limitations, evidence encourages and supports BoNT-A use as a safe and effective treatment modality for refractory idiopathic OAB in pediatric settings, regardless of dosage and target toxin. To the best of our knowledge, this is the first systematic review of the use of intravesical BoNT-A for idiopathic OAB treatment in children.

Diagnostic Accuracy of Serum Hyaluronan for Detecting HCV Infection and Liver Fibrosis in Asymptomatic Blood Donors.

Background: The disease caused by hepatitis C virus (HCV) is asymptomatic, silent, and progressive liver disease. In HCV-infected patients the increase in serum HA is associated with the development of hepatic fibrosis and disease progression. Methods: HCV-RNA detection was performed in all serological samples of blood donors that tested positive using HCV Ultra ELISA. Determination of hyaluronan (HA) was performed in positive HCV samples using ELISA-like fluorometric method. The HA content was compared to HCV viral load, genotype of the virus, liver fibrosis as well as ALT and GGT liver biomarkers. Results: Persistently normal ALT (<40 U/L) and GGT (<50 U/L) serum levels were detected in 75% and 69% of the HCV-Infected blood donors, respectively. Based on ROC analysis, the HA value < 34.2 ng/mL is an optimal cut-off point to exclude HCV viremia (specificity = 91%, NPV = 99%). Applying HA value ≥34.2 ng/mL significant liver fibrosis (≥F2) can be estimated in 46% of the HCV-infected blood donors. HA serum level (≥34.2 ng/mL) associated with a high ALT level (>40 U/mL) can correctly identify HCV infection and probable liver fibrosis (sensitivity = 96% and specificity = 90%) in asymptomatic blood donors. Conclusions: A high level of HA (≥34.2 ng/mL) in association with ALT (≥40 U/L) in serum can provide a good clinical opportunity to detect HCV-infected asymptomatic persons that potentially require a liver biopsy confirmation and antiviral treatment to prevent the development of advanced liver fibrosis or cirrhosis.

Zwitterionic Modification of Ultrasmall Iron Oxide Nanoparticles for Reduced Protein Corona Formation.

Polyacrylic-acid-coated ultra-small super-paramagnetic iron oxide nanoparticles were surface-modified with low-molecular-weight sulfobetaines or 3-(diethylamino)propylamine in order to generate nanoparticles with zwitterionic character (ZW-NPs). The ZW-NPs proved highly resistant to serum protein corona formation in vitro, as revealed by atomic force microscopy, SDS-PAGE and proteomics analysis, and exhibited low cytotoxicity towards A431 and HEK293 cells. The presence of unreacted carboxylic acid groups enabled additional functionalization with fluorescent (Cy5) and radioactive [64 Cu-dmptacn; dmptacn=1,4-bis(2-pyridinylmethyl)-1,4,7-triazacyclononane] moieties. Overall, the ZW-NPs represent promising platforms for the development of new multimodal diagnostic/therapeutic agents possessing "stealth" properties.

Zwitterionic-coated "stealth" nanoparticles for biomedical applications: recent advances in countering biomolecular corona formation and uptake by the mononuclear phagocyte system.

Nanoparticles represent highly promising platforms for the development of imaging and therapeutic agents, including those that can either be detected via more than one imaging technique (multi-modal imaging agents) or used for both diagnosis and therapy (theranostics). A major obstacle to their medical application and translation to the clinic, however, is the fact that many accumulate in the liver and spleen as a result of opsonization and scavenging by the mononuclear phagocyte system. This focused review summarizes recent efforts to develop zwitterionic-coatings to counter this issue and render nanoparticles more biocompatible. Such coatings have been found to greatly reduce the rate and/or extent of non-specific adsorption of proteins and lipids to the nanoparticle surface, thereby inhibiting production of the "biomolecular corona" that is proposed to be a universal feature of nanoparticles within a biological environment. Additionally, in vivo studies have demonstrated that larger-sized nanoparticles with a zwitterionic coating have extended circulatory lifetimes, while those with hydrodynamic diameters of ≤5 nm exhibit small-molecule-like pharmacokinetics, remaining sufficiently small to pass through the fenestrae and slit pores during glomerular filtration within the kidneys, and enabling efficient excretion via the urine. The larger particles represent ideal candidates for use as blood pool imaging agents, whilst the small ones provide a highly promising platform for the future development of theranostics with reduced side effect profiles and superior dose delivery and image contrast capabilities.

17ß-Estradiol and steady-state concentrations of H2O2: antiapoptotic effect in endometrial cells from patients with endometriosis.

Increased levels of hydrogen peroxide (H2O2) can initiate protective responses to limit or repair oxidative damage. However, H2O2 signals also fine-tune responses to growth factors and cytokines controlling cell division, differentiation, and proliferation. Because 17ß-estradiol (E2) also plays important roles in these processes, and is considered a major risk factor in the development and progression of endometriosis, this study evaluated whether E2 has an antiapoptotic effect on oxidative stress in endometrial cells in combination with steady-state H2O2 levels ([H2O2]ss). Endometrial stromal cells were prepared from the eutopic endometrium of 18 women with and without endometriosis to produce primary cells. These cells were stimulated with E2 for 20h, exposed to [H2O2]ss, and examined for cell viability, proliferation, and apoptosis. The endometrial cells from women with endometriosis maintained the steady state for 120min at high H2O2 concentrations. When they were pretreated with E2 and exposed to [H2O2]ss, a decrease in apoptosis level was observed compared to the control cells (p<0.01). The endometrial cells from patients with endometriosis subjected to both E2 and [H2O2]ss showed increased ERK phosphorylation. These findings suggested that H2O2 is a signaling molecule that downregulates apoptosis in endometrial cells, supporting the fact that endometriosis, albeit a benign disease, shares some features with cancer such as decreased catalase levels. These results link the E2 effects on [H2O2]ss to resistance to apoptosis and progression of endometriosis.

Nanomaterials: applications in cancer imaging and therapy.

The application of nanomaterials (NMs) in biomedicine is increasing rapidly and offers excellent prospects for the development of new non-invasive strategies for the diagnosis and treatment of cancer. In this review, we provide a brief description of cancer pathology and the characteristics that are important for tumor-targeted NM design, followed by an overview of the different types of NMs explored to date, covering synthetic aspects and approaches explored for their application in unimodal and multimodal imaging, diagnosis and therapy. Significant synthetic advances now allow for the preparation of NMs with highly controlled geometry, surface charge, physicochemical properties, and the decoration of their surfaces with polymers and bioactive molecules in order to improve biocompatibility and to achieve active targeting. This is stimulating the development of a diverse range of nanometer-sized objects that can recognize cancer tissue, enabling visualization of tumors, delivery of anti-cancer drugs and/or the destruction of tumors by different therapeutic techniques.

High prevalence of celiac disease in Brazilian blood donor volunteers based on screening by IgA antitissue transglutaminase antibody.

OBJECTIVE: To study the prevalence of celiac disease among blood donor volunteers based on screening by IgA antitissue transglutaminase antibody, followed by a confirmatory small intestine biopsy. METHODS: The transversal study involved 3000 potential blood donors, residing in the city of Sao Paulo, Brazil. The participants were gender divided into 1500 men and 1500 women, with an average age 34.4+/-10.8 years, and included blood donor volunteers who could be turned down owing to anemia. All participants answered a questionnaire concerning the presence of diarrhea, constipation or abdominal pain during the 3 months before the study. Each participant with human recombinant IgA antitissue transglutaminase antibody level above 10 U/ml was invited to undergo a small intestine biopsy by means of an upper gastrointestinal endoscopy. The presence of villous atrophy and a positive antibody test were suggestive of possible celiac disease. RESULTS: Antitissue transglutaminase antibody was positive in 1.5% (45/3000) of the study population. Among the antibody-positive group, 21 (46.6%) agreed to have a biopsy performed, and within them the histological pattern of villous atrophy was confirmed in 66.7% (14/21). Consequently, the suggestive prevalence of celiac disease was at the minimum, one per 214 of the potential blood donor volunteers. A significant association was found between celiac disease and the symptoms of diarrhea, constipation and abdominal pain. CONCLUSIONS: The prevalence of celiac disease in Sao Paulo city is high and comparable to that observed in European countries. It is possible that in Brazil the prevalence of this disease had previously been underestimated.