Prevention of HIV-1 gp120-induced neuronal damage in the central nervous system of transgenic mice by the NMDA receptor antagonist memantine

To investigate the in vivo role of NMDA receptor stimulation in HIV-1-related CNS neurotoxicity, we evaluated the neuroprotective potential of the NMDA receptor antagonist memantine in transgenic mice which have gp120-induced CNS damage. Brains of mice treated chronically with memantine and of untreated controls were analysed for structural damage by laser scanning confocal microscopy of sections immunolabeled for microtubule-associated protein-2 (MAP-2) and synaptophysin. Qualitative and quantitative analysis of confocal images revealed that memantine treatment substantially decreased neuropathology in gp120 transgenic mice; this included statistically significant improvements in both dendritic and presynaptic terminal density. These results provide in vivo evidence that gp120 can activate neurotoxic pathways that can ultimately result in aberrant NMDA receptor stimulation and neuronal damage in the CNS. They also suggest that clinically tolerated NMDA receptor antagonists may be useful in the prevention of neuronal damage in HIV-1-infected patients.     

Soluble adhesion molecules and angiotensin-converting enzyme in dementia

We aimed to determine plasma and cerebrospinal fluid (CSF) levels of angiotensin-converting enzyme (ACE) and the soluble forms of intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1) and platelet endothelial cell adhesion molecule-1 (sPECAM-1) as surrogate markers for endothelial cell activation in clinically diagnosed patients with Alzheimer's disease (AD, n=260), dementia with Lewy bodies (DLB, n=39) and non-demented controls (n=34). Plasma sICAM-1 and sPECAM-1 were higher and CSF sVCAM-1 were lower in AD and DLB patients than in controls (p<0.001). DLB patients had higher CSF sICAM-1, but lower CSF sVCAM-1 (p<0.001). No difference in ACE levels was found between the dementia groups and controls. In controls and AD patients CSF sICAM and sVCAM-1 strongly correlated with each other and with blood barrier permeability whereas in DLB group these correlations were weaker. The observed patterns in adhesion molecules may reflect distinctions in the pathophysiological basis of their generation in dementia patients.     

Lower limb motor restlessness in Asperger's disorder, measured using actometry

The movement disturbances and brain imaging findings in Asperger's disorder (AD) suggest a dopaminergic deficit in movement regulation. Movement disorders of different etiologies have been quantified and specified with actometry. We compared 10 AD patients with 10 healthy controls, measuring their rest-activities by actometry. The lower limb motor activity was significantly higher in the AD group. They also displayed a rhythmic, periodic movement pattern similar to akathisia. These findings suggest a hypothesis of idiopathic akathisia and a special sensitivity to adverse effects of neuroleptic drugs.     

Comparison of genotoxic and inflammatory effects of particles generated by wood combustion, a road simulator and collected from street and subway

The health effects of exposure to airborne particles are of increasing concern in society. In order to protect public health, a clarification of the toxic properties of particles from different sources is of importance. The aim of this study was to investigate and compare the genotoxicity and the ability to induce inflammatory mediators of nine different particle types from wood and pellets combustion, from tire-road wear and collected from an urban street and a subway station. The comet assay was used to assess genotoxicity after exposure of the human lung cell line A549. Inflammatory effects were measured as induction of IL-6, IL-8 and TNF-alpha after exposure of human macrophages. We found that all particles tested caused DNA damage and those from the subway caused more damage than the other particles (p<0.001) likely due to redox-active iron. In contrast, particles collected from an urban street were most potent to induce inflammatory cytokines. Particles from tire-road wear collected using a road simulator were genotoxic and able to induce cytokines. Finally, more effective combustion of wood led to less emission of particles, but those emitted did not show less toxicity in this study.     

Stimulated embryo production as a parameter of estrogenic exposure via sediments in the freshwater mudsnail Potamopyrgus antipodarum

The effects of three suspected endocrine disrupting chemicals, the xeno-estrogens bisphenol A (BPA), 4-tert-octylphenol (OP) and 4-n-nonylphenol (NP), were investigated in a whole-sediment biotest with the freshwater mudsnail Potamopyrgus antipodarum (Gastropoda, Prosobranchia). Artificial sediments were spiked with five nominal concentrations (six for NP), ranging from 1-300 microg/kg dry weight (1-1000 microg/kg for NP). After 2, 4 and 8 weeks of exposure, the responses of the test species were analysed. P. antipodarum exhibited a distinct increase in the number of embryos sheltered in its brood pouch in a time- and concentration-dependent manner in comparison to the solvent control sediment for BPA and OP. The number of "new", still unshelled embryos turned out to be the most sensitive parameter. The lowest observed effect concentration (LOEC) was equivalent to the lowest administered concentration (1 microg/kg for each test compound) for most parameters after 8 weeks of exposure. The calculation of effect concentrations resulted in even lower values for BPA (unshelled embryos after 2 weeks: EC(10) 0.22 microg BPA/kg, EC(50) 24.5 microg BPA/kg; after 4 weeks: EC(10) 0.19 microg BPA/kg, EC(50) 5.67 microg BPA/kg) and OP (unshelled embryos after 4 weeks: EC(10) 4 ng OP/kg, EC(50) 0.07 microg OP/kg). For NP, there was no clear concentration-dependent response, and therefore, no EC(10) or EC(50) could be estimated, but the data suggest an inverted u-shape type of curve. The LOEC in the experiments with NP was 10 microg/kg. Our results indicate that P. antipodarum is highly sensitive to the tested endocrine disruptors at environmentally relevant concentrations. Furthermore, the biotest with P. antipodarum is a useful tool for the identification of sediment-bound pollutants and for the assessment of sediment quality.     

Is the decline of the increasing incidence of non-Hodgkin lymphoma in Sweden and other countries a result of cancer preventive measures?

Is the decline of the increasing incidence of non-Hodgkin lymphoma (NHL) in Sweden and other countries a result of cancer preventive measures? The yearly age-standardized incidence of NHL increased significantly in Sweden during 1971-1990, for men an average of 3.2% and for women 3.1%. The corresponding figures for 1991-2000 were -0.8% and -0.2%, respectively. A decline of the increasing incidence has also been seen in other countries, such as the United States, Finland, and Denmark. Immunosuppression is one established risk factor for NHL, possibly with interaction with Epstein-Barr virus. Phenoxyacetic acids and chlorophenols, both pesticides, have been associated with NHL. Use of these chemicals was banned in Sweden in 1977 and 1978, respectively. Also, persistent organic pollutants such as polychlorinated biphenyls, hexachlorobenzene, chlordanes, and dioxins have been shown to increase the risk. Exposure of the whole population occurs predominantly through the food chain. Exposure to such chemicals was highest in the 1960s and 1970s. Because of regulation in the 1970s, exposure has declined substantially in the population. The change in incidence of NHL in Sweden and other countries may serve as a good example of how prohibition and limitation of exposure may be reflected in cancer statistics some decades later.     

Rotavirus in diarrheal children in rural Burkina Faso: High prevalence of genotype G6P[6]

Group A rotavirus (RVA) is the most common cause of severe gastroenteritis in young children globally, and responsible for a significant number of deaths in African countries. While vaccines are available, trials have shown a lesser efficacy in Africa. One of the reasons could be the prevalence and/or emergence of unusual or novel RVA strains, as many strains detected in African countries remain uncharacterized.In this study, we characterized RVA positive specimens from two remote rural areas in Burkina Faso, West Africa. In total 56 RVA positive specimens were subgrouped by their VP6 gene, and G-and P typed by PCR and/or sequencing of the VP7 and VP4 genes, respectively.Notably, we found a high prevalence of the unusual G6P[6]SGI strains (23%). It was the second most common constellation after G9P[8]SGII (32%); and followed by G1P[8]SGII (20%) and G2P[4]SGI (9%). We also detected a G8P[6]SGI strain, for the first time in Burkina Faso. The intra-genetic diversity was high for the VP4 gene with two subclusters within the P[8] genotype and three subclusters within the P[6] genotype which were each associated with a specific G-type, thereby suggesting a genetic linkage. The G6P[6]SGI and other SGI RVA strains infected younger children as compared to SGII strains (p < 0.05).To conclude, in this study we observed the emergence of unusual RVA strains and high genetic diversity of RVA in remote rural areas of Burkina Faso. The results highlight the complexity of RVA epidemiology which may have implication for the introduction of rotavirus vaccines currently being evaluated in many African countries.