High resolution analysis of paired helical filaments in Alzheimer's disease

Results of this comparative study indicated that electron microscopy of supra-ultrathin sections provided the best resolution, revealing the subunit structures, globules (32 Å ± 4), and longitudinal bars (47 Å ± 6) of paired helical filaments (PHF). A three-dimensional model of PHF substructure is therefore presented. The image of brightfield electron micrographs of isolated PHF positively stained with 2% phosphotungstic acid (PTA) also provided high resolution and revealed the presence of the beaded structures of these heavily stained filaments in the crossing-over region of PHF. Noisy background of the negatively stained preparation of isolated PHF substantially reduced the resolution. Severe flattened morphology of this preparation further complicated the interpretation of image analysis. Darkfield electron micrographs offered high-image contrast with low noise in the background clearly demonstrating the ropelike twisting configuration of PHF, but did not reveal the substructures of PHF. The tilting (±45°) analysis of these PHF prepared by uranyl acetate staining and rotary-shadowing and unidirectional shadowing methods with platinum showed that these heavy metals were deposited on the top filaments (away from the carbon film on the grid) in the crossing-over region of PHF.     

Three-dimensional reconstruction of senile plaques in Alzheimer's disease

So far, the three-dimensional approach to senile plaques, one of the principal histopathological hallmarks in Alzheimer's disease besides neurofibrillary tangles, has been scarce. Two main problems in three-dimensional reconstruction of histological specimens are the horizontal distortion during the preparation of serial thin tissue-slides and the need for consecutive vertical readjustment. This is greatly facilitated by the reflection contrast microscope (Leica, Germany) which is a light microscopical instrument causing interference patterns and reflections along interfaces by means of circularly polarized epi-illumination. Using this technique, one can obtain distinct optical sections of a depth of 1.5 μm within specimens up to 30 μm in thickness, thus preserving the integrity of the observed object and rendering a manual alignment superfluous. We applied the reflection contrast microscope (RCM) on thick tissue-slides of the cerebral cortex of a patient suffering from Alzheimer's disease which had been dyed according to Campbell. This is a silver-based staining method detecting βA4-amyloid, the main component of senile plaques. Under the RCM, these silver-stained extracellular amyloid deposits cause reflections which allow the assessment of their three-dimensional distribution by focusing through the specimen. The optical sections obtained in this way were digitized, and the identified senile plaques reconstructed by the grey-scale image analysis system VIDAS 2.5 (Zeiss/Kontron, Germany).     

Innervation of cerebral blood vessels: morphology, plasticity, age-related, and Alzheimer's disease-related neurodegeneration

The light microscopical and ultrastructural morphology of the innervation of the major cerebral arteries and pial vessels is described, including the origins of the different groups of nerve fibres and their characteristic neurotransmitter phenotype. Species and region specific variations are described and novel data regarding the parasympathetic innervation of cerebral vessels are presented. The dynamic nature, or plasticity, of cerebrovascular innervation is emphasized in describing changes affecting particular subpopulations of neurons during normal ageing and in Alzheimer's disease. The molecular controls on plasticity are discussed with particular reference to target-associated factors such as the neurotrophins and their neuronal receptors, as well as extracellular matrix related factors such as laminin. Hypotheses are presented regarding the principal extrinsic and intrinsic influences on plasticity of the cerebrovascular innervation.     

Distribution of sex steroid hormone receptors in the avian brain: functional implications for neural sex differences and sexual behaviors

Developmental and seasonal changes in the production of androgens, estrogens, and progestins seem to control sex-specific differentiation and seasonal changes in appetitive and consummatory sexual behaviors of birds. This results in profound sex differences in the quality (sex-specific) or quantity (sex-typical) of behaviors such as courtship, territoriality, or copulation. Steroids affect the brain by binding to intracellularly located receptors. The same brain areas express androgen, estrogen, and progesterone receptors in male and female brains. Sex differences in these genetically determined patterns occur in the size of neuron populations that intrinsically express sex steroid receptors. Further permanent sex differences are subsequent to degenerative fates of receptor expressing neuron populations during ontogeny. Transient sex differences in receptor expression appear to be due to area-specific up- and down-regulation of receptor levels, reflecting transient changes in the level of circulating steroids, changes in environmental conditions, or in the physiological status of the individuals. In particular, intrinsic sex differences in the expression pattern of sex steroid receptors and steroid-independent regulation of the expression level of these receptors in the brain are limiting mechanisms for gonad-dependent sexual development and activities.     

Studies of the Synthesis and Utilisation of Schiff's Bases: I. Schiff's Bases as Antioxidants for Lubricating Greases

Three Schiff's bases have been prepared as antioxidants for three grades of lubricating grease. The following Schiff's base compounds were synthesised: 3‐[(p‐chlorophenyl)iminomethylenyl]‐4‐hydroxy‐8‐methyl‐2(1H)‐quinolinone and its bromo and iodo analogues. The structures of these compounds have been confirmed using elemental analysis, nuclear magnetic resonance, and infrared spectroscopy. The quinolinone compounds were added to the lubricating greases in different concentrations. The antioxidant efficiency of these bases have been determined using infrared spectroscopy and total acid number. The results indicate that the oxidation stability of the lubricating greases is affected by the type of fatty acid they contain. It was found that the three types of grease resist oxidation in the presence of the Schiff's bases; the efficiency of these compounds as antioxidants decreases in the order: p‐chloro > p‐bromo > p‐iodo derivative. The mechanisms of operation of the quinolinone derivatives as scavengers for free radicals are suggested.     

Application of hand grip signals for an objective evaluation of Parkinson disease: Analysis and comparison with standard functional clinical tests

Evaluation of Parkinson pathology is usually done with the use of ratings made with different motor functional scales. The trouble with this practice is that it is subjective, difficult and it often happens that the results of different tests clash between theirs. To overcome these limitations the authors propose the evaluation and the quantification of Parkinson disease by means of suitable biomedical parameters linked to the primary parkinsonian symptoms.Twelve biomedical quantities have been defined to describe the behavior of hand grip signal; these parameters have been analyzed with statistical methods and their statistical significance has been determined to attain differentiation between pathologic and healthy subjects.The test results highlight that only the parameters related to the dynamics of the analyzed signals (such as space-time and strength quantities) show very significant statistical difference and can be used to assess Parkinson pathology. Their use represents one attempt to take evaluation objective and very simple.Finally, a comparative analysis of the results obtained in our study and those achieved from standard functional disability tests has been carried out highlighting the more meaningful correlations. The comparative tests show meaningful correlations that confirm and validate the goodness of the proposed parameters.