Farbsinnstörung nach Kopfschussverletzung

Ohne Zusammenfassung     

Evaluation of processing methods to equitably aliquot sputa for mycobacterial testing

We compared bacillary loads after splitting sputum specimens by chemical (N-acetyl-l-cysteine [NALC]) and mechanical homogenization by vortexing with sterile glass beads. NALC and vortexing with glass beads were equally effective at homogenizing sputum specimens, resulting in an equal distribution of tubercle bacilli in the aliquots.     

Photochemical internalization: a new tool for drug delivery

The utilisation of macromolecules in the therapy of cancer and other diseases is becoming increasingly important. Recent advances in molecular biology and biotechnology have made it possible to improve targeting and design of cytotoxic agents, DNA complexes and other macromolecules for clinical applications. In many cases the targets of macromolecular therapeutics are intracellular. However, degradation of macromolecules in endocytic vesicles after uptake by endocytosis is a major intracellular barrier for the therapeutic application of macromolecules having intracellular targets of action. Photochemical internalisation (PCI) is a novel technology for the release of endocytosed macromolecules into the cytosol. The technology is based on the activation by light of photosensitizers located in endocytic vesicles to induce the release of macromolecules from the endocytic vesicles. Thereby, endocytosed molecules can be released to reach their target of action before being degraded in lysosomes. PCI has been shown to stimulate intracellular delivery of a large variety of macromolecules and other molecules that do not readily penetrate the plasma membrane, including type I ribosome-inactivating proteins (RIPs), DNA delivered as gene-encoding plasmids or by means of adenovirus or adeno-associated virus, peptide nucleic acids (PNAs) and chemotherapeutic agents such as bleomycin and in some cases doxorubicin. PCI of PNA may be of particular importance due to the low therapeutic efficacy of PNA in the absence of an efficient delivery technology and the 10-100-fold increased efficacy in combination with PCI. The efficacy and specificity of PCI of macromolecular therapeutics has been improved by combining the macromolecules with targeting moieties, such as the epidermal growth factor. In general, PCI can induce efficient light-directed delivery of macromolecules into the cytosol, indicating that it may have a variety of useful applications for site-specific drug delivery as for example in gene therapy, vaccination and cancer treatment.     

The relationship between age and risky injecting behaviours among a sample of Australian people who inject drugs

Background

Limited evidence suggests that younger people who inject drugs (PWID) engage in high-risk injecting behaviours. This study aims to better understand the relationships between age and risky injecting behaviours.

Methods

Data were taken from 11 years of a repeat cross-sectional study of sentinel samples of regular PWID (The Australian Illicit Drug Reporting System, 2001–2011). Multivariable Poisson regression was used to explore the relationship between age and four outcomes of interest: last drug injection occurred in public, receptive needle sharing (past month), experiencing injecting-related problems (e.g. abscess, dirty hit; past month), and non-fatal heroin overdose (past six months).

Results

Data from 6795 first-time study participants were analysed (median age: 33 years, interquartile range [IQR]: 27–40; median duration of injecting: 13 years [IQR: 7–20]). After adjusting for factors including duration of injecting, each five year increase in age was associated with significant reductions in public injecting (adjusted incidence rate ratio [AIRR]: 0.90, 95% confidence interval [CI]: 0.88–0.92), needle sharing (AIRR: 0.84, 95% CI: 0.79–0.89) and injecting-related problems (AIRR: 0.96, 95% CI: 0.95–0.97). Among those who had injected heroin in the six months preceding interview, each five year increase in age was associated with an average 10% reduction in the risk of heroin overdose (AIRR: 0.90, 95% CI: 0.85–0.96).

Conclusions

Older PWID report significantly lower levels of high-risk injecting practices than younger PWID. Although they make up a small proportion of the current PWID population, younger PWID remain an important group for prevention and harm reduction.     

An improved method to generate equine dendritic cells from peripheral blood mononuclear cells: divergent maturation programs by IL-4 and LPS

Equine dendritic cells (eqDC) can be generated from peripheral blood monocytes by propagation in GM-CSF and IL-4. Despite similarities with the generation of human DC, we found significant improvements for eqDC generation and functional influences on eqDC maturation. The fractionation of peripheral blood mononuclear cells (PBMC) by two subsequent gradients at densities of 1.090 and 1.077 as well as an adherence step in AIM V((R)) medium on dishes coated with extracellular matrix components (Primaria) improved the purity and yield of DC. After 3 days, eqDC cultures with GM-CSF alone developed into three subsets of (i) MHC II(neg) cells, (ii) MHC II(low) immature, endocytic cells and (iii) MHC II(high) spontaneously mature, non-endocytic DC. The immature DC fraction of the GM-CSF cultures matured, as detected by MHC II up-regulation, upon LPS exposure overnight. DC cultures in GM-CSF plus IL-4 resulted in higher cell yields, a loss of the immature MHC II(low) population but increased mature MHC II(high) DC, suggesting maturation. However, the MHC II(high) DC fraction was still endocytically active and did not lose their endocytic function after LPS treatment. They marginally up-regulated MHC II expression but this did not result in an enhanced stimulation of an allogeneic mixed lymphocyte reaction. However, LPS treatment clearly induced mRNA for IL-12p35 and p40, which was not observed by addition of IL-4 alone. Together our data indicate that IL-4 and LPS induce two different maturation programs. IL-4 induces a semi-maturation where the cells are still endocytic, which can be further matured to secrete cytokines in a second step by LPS.     

A review of trends in the distribution of vector-borne diseases: is international trade contributing to their spread?

It is difficult to determine the part that international trade has played in the expansion of vector-borne diseases, because of the multitude of factors that affect the transformation of habitats and the interfaces between vectors and hosts. The introduction of pathogens through trade in live animals or products of animal origin, as well as the arrival of arthropod vectors, is probably quite frequent but the establishment of an efficient transmission system that develops into a disease outbreak remains the exception. In this paper, based on well-documented examples, the authors review the ecological and epidemiological characteristics of vector-borne diseases that may have been affected in their spread and change of distribution by international trade. In addition, they provide a detailed analysis of the risks associated with specific trade routes and recent expansions of vector populations. Finally, the authors highlight the importance, as well as the challenges, of preventive surveillance and regulation. The need for improved monitoring of vector populations and a readiness to face unpredictable epidemiological events are also emphasised, since this will require rapid reaction, not least in the regulatory context.     

Transient depletion of regulatory T cells in transgenic mice reactivates virus-specific CD8+ T cells and reduces chronic retroviral set points

Although chronic infections with viruses such as HIV and hepatitis C virus have been associated with regulatory T cell (Treg)-mediated suppression of virus-specific CD8(+) T-cell activity, no causal relationship between Tregs and chronic viral set points has been established. Using transgenic mice in which Tregs can be selectively ablated, we now show that transient depletion of Tregs during a chronic retroviral infection allows exhausted CD8(+) T cells to regain antiviral functions, including secretion of cytokines, production of cytotoxic molecules, and virus-specific cytolytic activity. Furthermore, short-term Treg ablation resulted in long-term reductions in chronic virus loads. These results demonstrate that Treg-mediated immunosuppression can be a significant factor in the maintenance of chronic viral infections and that Treg-targeted immunotherapy could be a valuable component in therapeutic strategies to treat chronic infectious diseases.