Insulin inhibits amyloid beta-induced cell death in cultured human brain pericytes

Amyloid-beta (Abeta) deposition in the cerebral arterial and capillary walls is one of the characteristics of Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis-Dutch type. In vitro, Abeta1-40, carrying the "Dutch" mutation (DAbeta1-40), induced reproducible degeneration of cultured human brain pericytes (HBP), by forming fibrils at the cell surface. Thus, this culture system provides an useful model to study the vascular pathology seen in Alzheimer's disease. In this study, we used this model to investigate the effects of insulin on Abeta-induced degeneration of HBP, as it has been mentioned previously that insulin is able to protect neurons against Abeta-induced cell-death. The toxic effect of DAbeta1-40 on HBP was inhibited by insulin in a dose-dependent matter. Insulin interacted with Abeta and inhibited fibril formation of Abeta in a cell-free assay, as well as at the cell surface of HBP. Our data indicate that the formation of a fibril network is essential for Abeta-induced cell death in HBP. Additionally, insulin may be involved in the regulation of Abeta fibrillization in AD.     

Oxatomide protectsTrichinella spiralis infected mice from lethal anaphylaxis

Infection withTrichinella spiralis in mice was accompanied by allergic sensitization as evidenced by anaphylactic death after intravenous injection of the antigen. Pre-treatment of the animals with oxatomide, a new orally active antiallergic drug, resulted in significant protection of the animals; the lowest effective dose of the compound was 1.25 mg/kg orally. In contrast to cyproheptadine, oxatomide offered little protection against serotonin toxicity in mice.The present data suggest that, in this model of systemic hypersensitivity, the anti-anaphylactic effect of oxatomide can be attributed mainly to inhibition of release of allergic mediators.     

Assessment of fibronectin conformation adsorbed to polytetrafluoroethylene surfaces from serum protein mixtures and correlation to support of cell attachment in culture

Surfaces of polytetrafluoroethylene (PTFE) were exposed to buffered aqueous solutions containing radio-labeled human fibronectin ([125I]Fn), Fn/bovine serum albumin (BSA) binary mixtures of various ratios or whole human plasma dilutions for 1 h. Total adsorbed Fn and albumin adsorption following rinsing was quantified on this surface. 125I-labeled monoclonal antibodies against either the tenth type-III Fn repeat unit (containing the cell-binding RGDS integrin recognition motif) or the Fn amino-terminal domain were used to probe the accessibility of each of these respective Fn regions post-adsorption. Human umbilical vein endothelial cells (HUVECs) were cultured on PTFE surfaces pre-exposed to each of these protein adsorption conditions and compared to identical conditions on tissue culture polystyrene (TCPS). Fn adsorption to PTFE is dependent upon the concentration of albumin co-adsorbing from solution: albumin out-competes Fn for PTFE surface sites even at non-physiological Fn/HSA ratios 10-100-fold biased in Fn. Antibodies against Fn do not readily recognize Fn adsorbed on PTFE as the HSA co-adsorption concentration in either binary mixtures or in plasma increases, indicating albumin masking of adsorbed Fn. At Fn/HSA ratios rich in Fn (1:1, 1:100), albumin co-adsorption actually improves anti-Fn antibody recognition of adsorbed Fn. HUVEC attachment efficiency to PTFE after protein adsorption correlates with amounts of Fn adsorbed and levels of anti-Fn antibody recognition of Fn on PTFE, linking cell attachment to integrin recognition of both adsorbed Fn density and Fn adsorbed conformation on PTFE surfaces.     

Inter-relationships between pituitary-adrenal hormones and catecholamines during a 6-day Nordic ski race

Summary The aim of the study was to investigate the inter-relationships between pituitary-adrenal hormones and catecholamines during a prolonged competition over 6 days. Plasma adrenocorticotropic hormone (ACTH), cortisol (C), -endorphin (EP), free and sulphated adrenaline (A) and noradrenaline (NA) were measured in 11 volunteer male subjects during a national Nordic-ski race (323 km). Blood samples were obtained before the competition in the evening as control (D₀), and before and after each day's racing (D₁–D₆). The mean daily heart rate (f _c) was calculated fromf _c values recorded every minute during the race. The results showed the following: changes in meanf _c [from 147 (SEM 3) to 156 (SEM 3) beats · min^–1 according to the day] were not significant during the race. Diurnal variations in ACTH, EP and C were no longer apparent after the race: evening levels were higher than their respective D₀ values during the race, except on D₃ when there was a lack of response to exercise in the three hormones. Unlike ACTH and EP, pre- and postexercise C values on D₁ and D₂ were higher than those on the subsequent days (P<0.001). In contrast, there was a progressive accumulation of A and NA in pre-and postrace concentrations which reached a plateau in about 4 days. Positive correlations between exercise responses in ACTH, C and EP were found especially on D₃ and D₆ (P<0.001) but there were no significant correlations between catecholamines and the other three hormones. Thus, prolonged competition over 6 days evoked different control mechanisms for hormones of the pituitary-adrenal axis and catecholamines. A sustained catecholamine release and sympathetic activation induced a progressive NA and A accumulation during the race. In contrast, the lack of a response to exercise in ACTH, EP and C on D₃ suggested a dissociated central command for pituitary axis hormones and sympathetic adrenal activation. On the following days, the response to a lack of exercise, in spite of ACTH stimulation, may have reflected an adaptation of adrenal glands to prolonged stress.     

Clinical and epidemiological aspects of human bocavirus infection

Human bocavirus was recently described as a novel member of the Parvoviridae to infect humans. Based on accumulating clinical and epidemiological data the virus is currently being associated with respiratory infections in young children and infants and is furthermore discussed as causative agent of gastrointestinal illness.     

Human papillomavirus-positive tonsillar carcinomas: a different tumor entity?

Human papillomavirus (HPV) infections are thought to be one of the causal factors in the development of head and neck squamous cell carcinomas (HNSCC), particularly in tumors arising from the Waldeyer's tonsillar ring. We screened 98 carefully stratified HNSCC and different control tissues for the presence of HPV DNA by nested polymerase chain reaction (PCR) specific for genital- and Epidermodysplasia verruciformis (EV)-associated HPVs and by HPV16-specific single step PCR. Typing was performed by direct sequencing and/or sequencing of cloned amplimers. On average HNSCC showed rather low HPV DNA prevalences; 18% of the oral cavity cancers, 8% of nasopharyngeal cancers, 25% of hypopharyngeal cancers and 7% of laryngeal cancers were HPV DNA positive. In contrast, HPV sequences could be detected in 45% of the oropharyngeal cancers, particularly tonsillar carcinomas (58%). Tonsillar carcinomas were significantly more likely to be HPV positive than tumors from any other site ( P<0.001). All tonsillar cancers contained oncogenic HPV types, predominantly HPV16 (13 of 14; 93%). Unaffected tonsils were available from two of these patients, but both tested negative for HPV DNA. Furthermore, no HPV DNA could be found in tonsillar biopsy specimens from control groups. Localization and load of HPV DNA was determined in HPV16-positive tonsillar carcinomas, their metastases and in unaffected mucosa using laser-assisted microdissection and subsequent real time fluorescence PCR. We demonstrated that the HPV genome is located in the cancer cells, whereas the infection of normal mucosa is a rare event. Quantification of HPV16 DNA in samples of seven patients yielded viral loads from 6 to 153 HPV DNA copies per beta-globin gene copy and the load values in both locations were roughly comparable. These loads are comparable with data shown for other HPV-associated lesions. Statistical evaluation of data related to clinicopathological parameters showed a significant correlation of the HPV positivity of tonsillar carcinomas with tumor grading ( P=0.008) and alcohol consumption ( P=0.029). Taken together our findings show a preferential association of HPV DNA with tonsillar carcinomas. Furthermore our results argue for HPV-positive tonsillar carcinomas representing a separate tumor entity, which is less dependent on conventional HNSCC risk factors.     

Multiscale structure of sheet nacre

This work was conducted on Pinctada maxima nacre (mother of pearl) in order to understand its multiscale ordering and the role of the organic matrix in its structure. Intermittent-contact atomic force microscopy with phase detection imaging reveals a nanostructure within the tablet. A continuous organic framework divides each tablet into nanograins. Their shape is supposed to be flat with a mean extension of 45nm. TEM performed in the darkfield mode evidences that at least part of the intracrystalline matrix is crystallized and responds like a 'single crystal'. The tablet is a 'hybrid composite'. The organic matrix is continuous. The mineral phase is thus finely divided still behaving as a single crystal. It is proposed that each tablet results from the coherent aggregation of nanograins keeping strictly the same crystallographic orientation thanks to a hetero-epitaxy mechanism. Finally, high-resolution TEM performed on bridges from one tablet to the next, in the overlying row, did not permit to evidence a mineral lattice but crystallized organic bridges. The same organic bridges were evidenced by SEM in the interlaminar sequence.