Chronic delivery of antibody fragments using immunoisolated cell implants as a passive vaccination tool.

BACKGROUND: Monoclonal antibodies and antibody fragments are powerful biotherapeutics for various debilitating diseases. However, high production costs, functional limitations such as inadequate pharmacokinetics and tissue accessibility are the current principal disadvantages for broadening their use in clinic. METHODOLOGY AND PRINCIPAL FINDINGS: We report a novel method for the long-term delivery of antibody fragments. We designed an allogenous immunoisolated implant consisting of polymer encapsulated myoblasts engineered to chronically release scFv antibodies targeted against the N-terminus of the Aβ peptide. Following a 6-month intracerebral therapy we observed a significant reduction of the production and aggregation of the Aβ peptide in the APP23 transgenic mouse model of Alzheimer's disease. In addition, functional assessment showed prevention of behavioral deficits related to anxiety and memory traits. CONCLUSIONS AND SIGNIFICANCE: The chronic local release of antibodies using immunoisolated polymer cell implants represents an alternative passive vaccination strategy in Alzheimer's disease. This novel technique could potentially benefit other diseases presently treated by local and systemic antibody administration.

Diagnostic of Biomphalaria snails and Schistosoma mansoni: DNA obtained from traces of shell organic materials

Freshwater snails belonging to the genus Biomphalaria act as intermediate hosts for the parasite trematode Schistosoma mansoni in Africa and in the neotropical region. Identification of such molluscs is carried out based on morphological characters and the presence of cercariae is verified through squeezing snails between two glass slides or by exposing them to artificial light. However, sometimes, the material collected includes molluscs with decomposed bodies or, yet, only empty shells, which precludes their identification and S. mansoni detection. Due to these difficulties, we have developed a methodology in which DNA may be extracted from traces of organic material from inside shells in order to identify molluscs through polymerase chain reaction and restriction fragment length polymorphism and to detect S. mansoni into these snails, by using low stringency polymerase chain reaction. Species-specific profiles obtained from B. glabrata, B. straminea, and B. tenagophila snails and their shells, maintained in laboratory for ten years, showed the same profiles. S. mansoni profiles showed to be present in shell specimens as far as the eighth week after being removed from aquarium.

In vitro measurement of enzymatic markers as a tool to detect mouse cardiomyocytes injury

Primary cultures of cardiomyocytes represent a useful model for analyzing cardiac cell biology as well as pathogenesis of several cardiovascular disorders. Our aim was to standardize protocols for determining the damage of cardiac cells cultured in vitro by measuring the creatine kinase and its cardiac isotype and lactate dehydrogenase activities in the supernatants of mice cardiomyocytes submitted to different protocols of cell lysis. Our data showed that due to its higher specificity, the cardiac isotype creatine kinase was the most sensitive as compared to the others studied enzymatic markers, and can be used to monitor and evaluate cardiac damage in in vitro assays.

Biochemical analysis of female mice urine with reference to endocrine function: a key tool for estrus detection.

Species-specific chemical signals released through urine, sweat, saliva and feces are involved in communication between animals. Urinary biochemical constituents along with pheromones may contribute to variation across reproductive cycles and facilitate to estrus detection. Hence, the present study was designed to analyze such biochemical profiles, such as proteins, carbohydrates, lipids, fatty acids, in response with steroid hormones such as estradiol and progesterone. The experimental groups were normal, prepubertal, ovariectomized, and ovariectomized with estrogentreated female mice. In normal mice, the protein and lipid concentrations in urine were significantly higher in proestrus and estrus phases and the quantity of fatty acids was also comparatively higher in estrus. Furthermore, certain fatty acids, namely tridecanoic, palmitic and oleic acids, were present during proestrus and estrus phases, but were exclusively absent in ovariectomized mice. However, the carbohydrate level was equally maintained throughout the four phases of estrous cycle. For successful communication, higher concentrations of protein and specific fatty acids in estrus are directly involved. The significant increase in estradiol at estrus and progesterone at metestrus seems to be of greater importance in the expression pattern of biochemical constituents and may play a notable role in estrous cycle regulation. Thus, we conclude that the variations observed in the concentration of the biochemical constituents depend on the phase of the reproductive cycle as well as hormonal status of animals. The appearance of protein and specific fatty acids during estrus phase raises the possibility to use these as a urinary indicators for estrus detection.

Efficacy of an enzyme-linked immunosorbent assay as a diagnostic tool for schistosomiasis mansoni in individuals with low worm burden

IgM-ELISA is an immunoenzymatic method useful for detection of IgM antibodies against a fraction of Schistosoma mansoni adult worm antigen (AWA) that is soluble in trichloroacetic acid (AWA-TCA). This method was applied to three groups of individuals with different clinical and epidemiological characteristics, and the results compared with those obtained by other diagnostic methods: immunofluorescence test for detection of IgM antibodies (IgM-IFT) or IgG antibodies (IgG-IFT), ELISA for detection of IgG antibodies (IgG-ELISA), and two parasitological methods, Kato-Katz and miracidium hatching. The IgM-ELISA presented a sensitivity of 98%, when the parasitologic fecal examination was defined as reference diagnostic method, and a specificity of 98 and 97.3%, respectively for the group of clinically healthy individuals and other helminth carriers. A comparative analysis between the results of IgM-ELISA and those obtained by other serologic tests showed a good degree of agreement, with Kappa indices ranging from 0.95 to 0.98. The diagnostic efficacy of 97.8%, as determined with schistosomiasis patients with low parasitic burden, suggests the excellent performance of the IgM-ELISA and its usefulness for the diagnosis of schistosomiasis when applied in low endemic areas.

A DVD authoring tool for GNU/Linuxdesktop systems

Projecte denominat Mistelix, una eina d'autoria de DVD en codi obert per a sistemes GNU / Linux.

Health Risks and Health Inequalities in Housing: an Assessment Tool

This tool is designed to assess the health risks of housing and the residential environment at the scale of a neighbourhood, housing stock or administrative area. For each health risk, the tool enables a judgement to be recorded about the level of health risk attributable to unhealthy or unsafe housing conditions, and for this to be compared with the adequacy of local practice in mitigating the risk.

2007 Spearhead Health Inequalities Intervention Tool (and Press Release)

The Health Inequalities Intervention Tool, developed by APHO, highlights the key issues that Spearhead local authorities (with their PCTs) need to address to meet the Government۪s life expectancy targets. It can be used by any Spearhead Primary Care Trust or local council to find out what the underlying causes of the life expectancy gap are for that area. This Tool is designedto allow "Spearhead" Local Authorities/PCTs tounderstand better how they might reduce the inequalties between them and the national picture. (Please note that there are no "Spearhead" PCTs in the East of England. However, plans are being drawn up to address this and allow the developmentof this tool that is of use to all PCTs.)

Health Inequalities Intervention Tool. East of England. Draft Spec - Autumn 2007

Pilot approaches that will be used in the Phase 2 of National Health Inequalities Intervention Tool, due to be launched early 2008.

Health Inequalities Target Data Web Tool - Updated to 2003-05

This tool contains the data for the LHO briefing "The London Health Inequalities Forecast: A briefing on inequalities in life expectancy and deaths from cancers, heart disease and stroke in London". The tool enables local areas to monitor their progress towards the national health inequalities targets for life expectancy, mortality from heart disease and stroke, and mortality from cancers.

Spearhead Health Inequalities Intervention Tool: frequently asked questions

This document answers some common questions about the use of the Spearhead Health Inequalities Intervention Tool.

Spearhead Health Inequalities Intervention Tool: technical document

This document describes the technical detail behind the Spearhead Health Inequalities Intervention Tool.

Health Inequalities Intervention Tool (2008)

This tool is designed to support Primary Care Trusts with their Local Delivery Planning and commissioning

Health inequalities intervention tool: press release

The APHO Health Inequalities Tool provides health and local authorities with the information they need to reduce health inequalities in their local community. For the first time they will have hard-edged evidence at their fingertips that tells them the causes of their life expectancy gap and quantifies the impact of local actions

Health inequalities intervention tool instructions

Instructions on how to use the Health inequalities intervention tool and how to interpret the results.