Intranasal Dopamine Reduces In Vivo [(123)I]FP-CIT Binding to Striatal Dopamine Transporter: Correlation with Behavioral Changes and Evidence for Pavlovian Conditioned Dopamine Response

Dopamine (DA), which does not cross the blood-brain barrier, has central and behavioral effects when administered via the nasal route. Neither the mechanisms of central action of intranasal dopamine (IN-DA), nor its mechanisms of diffusion and transport into the brain are well understood. We here examined whether IN-DA application influences dopamine transporter (DAT) binding in the dorsal striatum and assessed the extent of binding in relation to motor and exploratory behaviors. We hypothesized that, based on the finding of increased extracellular DA in the striatum induced by application of IN-DA, binding of [(123)I]FP-CIT to the DAT should be decreased due to competition at the receptor

Genomic analysis reveals the molecular basis for capsule loss in the group B Streptococcus population

The human and bovine bacterial pathogen Streptococcus agalactiae (Group B Streptococcus, GBS) expresses a thick polysaccharide capsule that constitutes a major virulence factor and vaccine target. GBS can be classified into ten distinct serotypes differing in the chemical composition of their capsular polysaccharide. However, non-typeable strains that do not react with anti-capsular sera are frequently isolated from colonized and infected humans and cattle. To gain a comprehensive insight into the molecular basis for the loss of capsule expression in GBS, a collection of well-characterized non-typeable strains was investigated by genome sequencing. Genome based phylogenetic analysis extended to a wide population of sequenced strains confirmed the recently observed high clonality among GBS lineages mainly containing human strains, and revealed a much higher degree of diversity in the bovine population. Remarkably, non-typeable strains were equally distributed in all lineages. A number of distinct mutations in the cps operon were identified that were apparently responsible for inactivation of capsule synthesis. The most frequent genetic alterations were point mutations leading to stop codons in the cps genes, and the main target was found to be cpsE encoding the portal glycosyl trasferase of capsule biosynthesis. Complementation of strains carrying missense mutations in cpsE with a wild-type gene restored capsule expression allowing the identification of amino acid residues essential for enzyme activity

Continued Professional Education of Bulgarian Pharmacists: Second Registration Period

The continuing professional education prepares the pharmacists for the requirements of the changed role of pharmacists in the society. Different approaches to continuous professional education ranging from lectures to peer-mentoring work shops and web tools have been developed throughout the last 25 years. The goal of the current analysis is to systematize the trends in accredited education events for pharmacists by the Quality Committee of the BPhU during 2010-2013. This study is a retrospective database analysis. The information concerning the accredited forms of continuing education of pharmacists as well as other activities related to continuing education was extracted from the official protocols, issued by the Quality Commission of the Bulgarian Pharmaceutical Union (BPhU). The continuing postgraduate education of pharmacists in Bulgaria is developing with new elements which allow competence development through individual forms of self-development such as publication activities, delivering presentations, individual training, etc. In the educational programs accredited during the second registration period, still prevailed the short courses, with focus on the new medicinal products

Prevention of group B streptococcal neonatal disease revisited. The DEVANI European project

The purpose of this paper was to present the current knowledge on the prevention of group B streptococcus (GBS)neonatal infections and the status of prevention policies in European countries and to present the DEVANI pan-European program, launched in 2008. The aim of this program was to assess the GBS neonatal infection burden in Europe, to design a new vaccine to immunize neonates against GBS infections, to improve the laboratory performance for the diagnosis of GBS colonization and infection, and to improve the methods for the typing of GBS strains. The current guidelines for GBS prevention in different countries were ascertained and a picture of the burden before and after the instauration of prevention policies has been drawn. After the issue of the Centers for Disease Control and Prevention (CDC) guidelines, many European countries have adopted universal screening for the GBS colonization of pregnant women and intrapartum prophylaxis to colonized mothers. Nevertheless, some European countries continue advocating the risk factor approach to GBS prevention. Most European countries have implemented policies to prevent GBS neonatal infections and the burden of the disease has decreased during the last several years. Nevertheless, further steps are necessary in order to develop new strategies of prevention, to improve microbiological techniques to detect GBS colonization and infection, and to coordinate the prevention policies in the EU.the DEVANI Project, FP7 Health-F5-2007-20048

Acidic pH strongly enhances in vitro biofilm formation by a subset of hypervirulent ST-17 Streptococcus agalactiae strains

Streptococcus agalactiae, also known as group B Streptococcus (GBS), is a primary colonizer of the anogenital mucosa of up to 40% of healthy women and an important cause of invasive neonatal infections worldwide. Among the 10 known capsular serotypes, GBS type III accounts for 30 to 76% of the cases of neonatal meningitis. In recent years, the ability of GBS to form biofilm attracted attention for its possible role in fitness and virulence. Here, a new in vitro biofilm formation protocol was developed to guarantee more stringent conditions, to better discriminate between strong-, low-, and non-biofilm-forming strains, and to facilitate interpretation of data. This protocol was used to screen the biofilm-forming abilities of 366 GBS clinical isolates from pregnant women and from neonatal infections of different serotypes in relation to medium composition and pH. The results identified a subset of isolates of serotypes III and V that formed strong biofilms under acidic conditions. Importantly, the best biofilm formers belonged to serotype III hypervirulent clone ST-17. Moreover, the abilities of proteinase K to strongly inhibit biofilm formation and to disaggregate mature biofilms suggested that proteins play an essential role in promoting GBS biofilm initiation and contribute to biofilm structural stability. © 2014, American Society for Microbiology

International External Quality Assurance for Laboratory Identification and Typing of Streptococcus agalactiae (group B streptococci)

We report the results from the first international multicentre external quality assessment (EQA) studies for molecular and serological typing of group B streptococcus (GBS) strains as part of DEVANI (DEsign of a Vaccine Against Neonatal Infections), a pan-European programme. A questionnaire-based surveillance was undertaken amongst eight DEVANI and six non-DEVANI participating laboratories from 13 countries in order to assess their current microbiological procedures for GBS screening, diagnosis and typing. GBS strains from three EQA distributions were characterised using molecular and serological methods based on GBS capsular polysaccharide typing. Participants were asked to test the first distribution using their current serotyping and genotyping methods. Strep-B-Latex agglutination method was the most widely used method with a typeability value of >90%. A multiplex PCR assay for GBS capsular gene typing was also used by two of 14 centres who achieved a typeability value of 93%; this assay only detected 9 of 10 GBS capsular polysaccharide genes. From the second and third EQA studies standardised protocols were prepared for serological and molecular typing of GBS strains based on the Strep-B-Latex agglutination method and a novel multiplex PCR assay which detected all ten GBS capsular types (Ia to IX). These standardised protocols are being used by many European laboratories and as the use of these methods increase, it is imperative to continuously improve and assess laboratory performance and offer training to any laboratories that have technical difficulties.DEVANI: Design of a Vaccine Against Neonatal Infection