Human skin penetration of sunscreen nanoparticles: in-vitro assessment of a novel micronized zinc oxide formulation.

The extent to which topically applied solid nanoparticles can penetrate the stratum corneum and access the underlying viable epidermis and the rest of the body is a great potential safety concern. Therefore, human epidermal penetration of a novel, transparent, nanoparticulate zinc oxide sunscreen formulation was determined using Franz-type diffusion cells, 24-hour exposure and an electron microscopy to verify the location of nanoparticles in exposed membranes. Less than 0.03% of the applied zinc content penetrated the epidermis (not significantly more than the zinc detected in receptor phase following application of a placebo formulation). No particles could be detected in the lower stratum corneum or viable epidermis by electron microscopy, suggesting that minimal nanoparticle penetration occurs through the human epidermis.

Fibre diffraction of hair can provide a screening test for Alzheimer's disease: a human and animal model study.

BACKGROUND: Studies of molecular changes in hair as possible biomarkers for specific cancers revealed an additional molecular change in the diffraction patterns of some persons aged over 75. This change was found to correlate with the presence of Alzheimer's disease (AD). To confirm this correlation and its relation to the presence of a human APP mutation, known to definitely cause AD, hairs were examined from AD patients, pregnant women known to have an increase in plasma beta amyloid and transgenic mice carrying a mutated human APP gene. Patients were clinically examined by an experienced physician who recorded the patient's history and completed physical and neurological examinations. Hair samples were held taut and centred in the beam. The diffraction patterns were collected on Fuji-Bas Imaging plates and analysed using standard programs. MATERIAL/METHODS: A fan-shaped set of spot-like reflections was observed in the equatorial diffraction patterns from the hair of all AD patients and all third trimester pregnant women. Combined fibre diffraction of hair and histopathologic examination of brains from transgenic mice carrying a mutated human APP gene confirmed that these changes are related to the mutated human APP genes and the formation of beta amyloid plaques. RESULTS: Here we show results that fibre diffraction analysis would provide a non-invasive, accurate bio-marker for Alzheimer's disease. Our results are consistent with the hypothesis that this marker is related to the presence of mutated human APP genes and indicate that the structural change precedes the significant development of plaques. CONCLUSIONS: Here we show results that fibre diffraction analysis would provide a non-invasive, accurate bio-marker for Alzheimer's disease. Our results are consistent with the hypothesis that this marker is related to the presence of mutated human APP genes and indicate that the structural change precedes the significant development of plaques.

Reduction of inclusion body pathology in ApoE-deficient mice fed a combination of antioxidants.

Clinical studies have shown that the antioxidant vitamin E can slow the progression of Alzheimer's disease (AD). Other antioxidants reported to affect cognitive function include ginkgo biloba, vitamin C, and lipoic acid. To examine the effects of combination antioxidant therapy (CAT) on longevity and neuropathology in mice, we supplemented the diet of ApoE-deficient mice with vitamin E, ginkgo biloba, pycnogenol, and ascorbyl palmitate. ApoE-deficient mice normally exhibit increased numbers of PAS-positive inclusion bodies with aging. However, supplementation with CAT resulted in a significant increase in life span and a marked reduction of inclusion body histopathology in the hippocampus. In addition, while untreated apoE-deficient mice exhibited increased levels of TUNEL staining, a marker of DNA fragmentation, supplementation with CAT resulted in a significant reduction in the levels of TUNEL staining. These findings suggest that oxidative mechanisms, perhaps related to neuronal apoptosis, are integral to inclusion body formation in aging mice. The association between the reduced number of apoptotic cells and the reduction in inclusion bodies may explain in part the increased longevity of mice fed CAT, and supports the contention that the combined actions of selected antioxidants may be therapeutically effective against neurodegenerative diseases.

Altered glycosylation of acetylcholinesterase in APP (SW) Tg2576 transgenic mice occurs prior to amyloid plaque deposition.

Previous studies have shown that a minor glycoform of acetylcholinesterase (AChE) is increased in Alzheimer's disease brain and cerebrospinal fluid. This glycoform can be distinguished from other AChE species by its lack of binding to concanavalin A (Con A). In this study, the temporal relationship between AChE glycosylation and Abeta deposition was examined in Tg2576 mice. There was a significant (p < 0.05) difference in AChE glycosylation in Tg2576 mice compared with age-matched background strain control mice at 4 months of age. This difference in glycosylation was also observed in 8- and 12-month-old Tg2576 mice. In contrast, Abeta plaques were only seen in the Tg2576 mice at 12 months of age, and were not detected at 4 and 8 months of age. Soluble human-sequence Abeta was detected as early as 4 months of age in the transgenic mice. The altered AChE glycosylation was due to an increase in a minor AChE isoform, which did not bind Con A, similar to that previously observed to be increased in Alzheimer's disease brain and cerebrospinal fluid. The results demonstrate that in transgenic mice altered AChE glycosylation is associated with very early events in the development of AD-like pathology. The study supports the possibility that glycosylation may also be a useful biomarker of AD.