Uptake and toxicity of copper oxide nanoparticles in cultured primary brain astrocytes

To test for consequences of an exposure of brain cells to copper oxide nanoparticles (CuO-NPs), we synthesised and characterised dimercaptosuccinate-coated CuO-NPs. These particles had a diameter of around 5 nm as determined by transmission electron microscopy, while their average hydrodynamic diameter in aqueous dispersion was 136 ± 4 nm. Dispersion in cell-culture medium containing 10% fetal calf serum increased the hydrodynamic diameter to 178 ± 12 nm and shifted the zeta potential of the particles from –49 ± 7 mV (in water) to –10 ± 3 mV. Exposure of cultured primary brain astrocytes to CuO-NPs increased the cellular copper levels and compromised the cell viability in a time-, concentration- and temperature-dependent manner. Application of CuO-NPs in concentrations above 100 µM copper (6.4 µg/ml) severely compromised the viability of the cells, as demonstrated by a lowered 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction capacity, a lowered cellular lactate dehydrogenase activity and an increased membrane permeability for the fluorescent dye propidium iodide. Copper internalisation as well as cell toxicity of astrocytes exposed to CuO-NPs were similar to that observed for cells that had been incubated with copper salts. The CuO-NP-induced toxicity was accompanied by an increase in the generation of reactive oxygen species (ROS) in the cells. Both, ROS formation and cell toxicity in CuO-NP-treated astrocytes, were lowered in the presence of the cell-permeable copper chelator tetrathiomolybdate. These data demonstrate that CuO-NPs are taken up by cultured astrocytes and suggest that excess of internalised CuO-NPs cause cell toxicity by accelerating the formation of ROS.     

Gitelman syndrome DD thiazide diuretics abuse

Introduction. Gitelman syndrome (GS) is a rare inherited disorder. Mutations in SLC12A3 gene that encode tubular Na+Cl-cotransporter (NCCT) cause hypokalemic metabolic alkalosis, salt loss, hypomagnesaemia and hypocalciuria. The symptoms include weakness, vertigo, hypotension, tetany, paresthesia and nausea. Diagnostic criteria are a normal urine concentrating ability, normal glomerular filtration rate (GFR), hypomagnesaemia (<0,65mmol/l), hypokalemia (<3,6mmol/l) and hypocalciuria (<0,1mmol/mmol creatinine). Previously, the diagnosis was made by exclusion. Today, genetic analysis can ensure diagnosis. Thiazide diuretics (TD) abuse with similar abnormalities can make the differential diagnosis difficult. Causal therapy of GS does not exist. The substitution of potassium and magnesium are therapeutic strategies. Case presentation. A 41-year-old obese woman presented at the emergency department with recurrent episodes of hypokalemia with concomitant weakness, muscle cramps, polyuria and collapse. The results of laboratory testing of blood and urine led to the suspected diagnosis of GS. In the follow-up examinations, the results were inconsistent. Therefore, a transient thiazide diuretics abuse was assumed. Discussion. This case demonstrates the difficulties in making the diagnosis of GS on the basis of only clinical and laboratory tests, without the use of genetic analysis. The differentiation between GS and thiazide diuretic abuse is especially difficult.     

The temporal dynamics of inflected word recognition: A masked ERP priming study of French verbs

Morphological aspects of human language processing have been suggested by some to be reducible to the combination of orthographic and semantic effects, while others propose that morphological structure is represented separately from semantics and orthography and involves distinct neuro-cognitive processing mechanisms. Here we used event-related brain potentials (ERPs) to investigate semantic, morphological and formal (orthographic) processing conjointly in a masked priming paradigm. We directly compared morphological to both semantic and formal/orthographic priming (shared letters) on verbs. Masked priming was used to reduce strategic effects related to prime perception and to suppress semantic priming effects. The three types of priming led to distinct ERP and behavioral patterns: semantic priming was not found, while formal and morphological priming resulted in diverging ERP patterns. These results are consistent with models of lexical processing that make reference to morphological structure. We discuss how they fit in with the existing literature and how unresolved issues could be addressed in further studies.     

“It is easier for me to shoot up”: stigma,abandonment, and why HIV-positive drug users in Russia fail to link to HIV care

Many HIV-positive people who inject drugs (PWID) globally are not receiving HIV care. This represents a major challenge among key populations to end the global HIV epidemic. This qualitative study explored the process and associated barriers of linking HIV-positive PWID who are in addiction treatment to HIV care in St. Petersburg, Russia. We conducted three focus groups and seven semi-structured interviews with participants in the LINC (“Linking Infectious and Narcology Care”) project at addiction and HIV hospitals in St. Petersburg. The sample consisted of 25 HIV-infected patients with opioid dependence and seven health-care providers, including addiction and infectious disease physicians and case managers. A variety of intertwining factors influence effective engagement of PWID with HIV treatment. Stigma, problematic patient–provider relationships, and fragmented health care were the main challenges for HIV care initiation by PWID, which were further exacerbated by injection drug use. Effective linkage of PWID to HIV care requires acknowledging and addressing stigma’s role and different perspectives of patients and providers.     

A Cell-Free Collagen Type I Device for the Treatment of Focal Cartilage Defects

The purpose of this study was to evaluate the potential value of a cell-free collagen type I gel plug for the treatment of focal cartilage defects. Cellular migration and proliferation was addressed in vitro, and the formation of repair tissue in a nude mouse-based defect model. A cell-free plug made of collagen type I was placed in the center of an incubation plate. Surrounding space was filled with a collagen type I gel (Arthro Kinetics, Esslingen, Germany) seeded with 2 × 10⁵ human articular chondrocytes/mL gel. After cultivation for up to 6 weeks in vitro, samples were subject to histological and immunohistochemical staining and gene expression analysis. Subsequently, chondral defects of human osteochondral blocks were treated with the plug, and specimens were cultivated subcutaneously in nude mice for 6 weeks. The repair tissue was evaluated macroscopically, and collagen type II production was investigated immunohistochemically. In vitro, morphology of immigrated cells did not show any differences, as did collagen type II gene expression. After 4 weeks, the plug was homogeneously inhabited. After 6 weeks of cultivation in nude mice, collagen gel plug treatment led to a macroscopically excellent repair tissue. Histological staining revealed a tight bonding, and the collagen gel plug started to be remodeled. We conclude that the novel collagen gel plug device offers an environment favorable for the migration of articular chondrocytes and leads to a good-quality repair tissue in the nude mouse model. The arthroscopic transplantation of a collagen gel plug may be one option in the treatment of focal cartilage defects.     

Incidence and risk factors for community-acquired acute gastroenteritis in north-west Germany in 2004

In developed countries, acute gastroenteritis (AGE) is a major source of morbidity. However, only a few studies have estimated its incidence and the associated medical burden. This population-based study determined the incidence of community-acquired AGE patients seeking medical care and the relative role of various pathogens. Stool samples from patients with AGE presenting to a general practitioner (GP), pediatrician, or specialist in internal medicine for that reason were screened for various bacterial and viral enteropathogens. A control group was established as well. Incidences were calculated by the number of positive patients divided by the general population. The study was performed in north-west Germany in 2004. The incidence of AGE patients requiring medical consultation was 4,020/100,000 inhabitants. Children (<5 years of age) were at the highest risk (13,810/100,000 inhabitants). Of the patients, 6.6% were tested positive for an enteropathogenic bacteria and 17.7% for a viral agent. The predominant pathogens were norovirus (626/100,000) and rotavirus (270/100,000). Salmonella was the most frequently detected bacteria (162/100,000). The results presented confirm AGE and, specifically, AGE of viral origin as a major public health burden in developed countries.