Potential roles of protease inhibitors in Alzheimer's disease

Recently, protease inhibitors have been recognized as potential contributors to the pathogenesis of Alzheimer's disease. In this role, they could mediate an exaggerated regenerative response in the brain, participate as acute phase reactants, or be involved in the aberrant proteolytic processing of the amyloid proteins. Protease inhibitors are, therefore, attractive targets for drug intervention in Alzheimer's disease.     

Cytoskeletal rearrangement by oxidative stress

The cytoskeleton is susceptible to oxidative stress and this occurs prior to membrane blebbing and cell lysis. Vimentin intermediary filaments in rheumatoid synoviocytes are more susceptible than in normal synoviocytes and this may have pathological significance. They are however no more susceptible to heat shock than other cell types.     

TRH-induced reflex changes in patients with ALS

A trial of Thyrotropin Releasing Hormone (TRH) 5.0 mg/kg body weight subcutaneously every other day for two weeks produced transient increased tone in muscles, along with other (side-) effects in patients with Amyotrophic Lateral Sclerosis (ALS). One patient's extensor plantar transiently changed to a flexor plantar reflex after injection, probably due to disproportionate increase in tone of the calf muscles. No significant changes in F-waves or H-reflexes were seen. No increase in useful voluntary strength, or in strength measured by Medical Research Council (MRC) testing or strain gauge isometric strength testing was seen. However, dyspnea was seen within 10 minutes of TRH injection.     

Electrophysiologic evaluation of Emery-Dreifuss muscular dystrophy. A single fiber and quantitative EMG study

A 16-year-old boy, the only affected member of the family, noticed early onset contracture of the elbows, and developed slowly progressive humeroperoneal weakness and atrophy, and bilateral equinus. The severe restriction of the forward flexion of the neck and thoracolumbar spine, resembled a rigid spine syndrome. An electrocardiogram showed atrioventricular conduction abnormalities. Muscle biopsy was consistent with mild myopathy. The overall conventional findings of a detailed electromyographic study in the limbs and erector trunci muscles, as well as the results of conduction velocity, automatic analysis of the voluntary pattern and single fiber electromyography studies were consistent with myopathy, although some atypical findings were found. The controversy about neurogenic and myopathic features in Emery-Dreifuss disease is discussed. The unspecific value of the flexion limitation of the spine, and the uncertain nosological position of the rigid spine syndrome are also commented.     

Dynorphin-containing pilomotor neurons in the superior cervical ganglion of guinea pigs

Retrograde axonal tracing and double-labelling immunofluorescence have been combined to determine the neuropeptide content of identified pilomotor neurons in the superior cervical ganglion of guinea pigs. These neurons lacked immunoreactivity to neuropeptide Y (NPY) but they generally contained low levels of immunoreactivity to prodynorphin-derived peptides, including dynorphin A(1-8), dynorphin A(1-17), and alpha-neo-endorphin. Thus pilomotor neurons are neurochemically distinct from superior cervical ganglion cells which contain immunoreactivity to NPY and prodynorphin-derived peptides and which innervate the iris and most of the vasculature in the head of guinea pigs. They are also distinct from sympathetic secretomotor neurons which lack both NPY and prodynorphin-derived peptides.     

Behavioral neurology of multi-infarct dementia

Multi-infarct dementia (MID) is a heterogeneous entity in which a variety of cerebrovascular disorders leads to intellectual impairment. A variety of patterns of behavioral changes may be observed in MID, depression, psychosis, and personality change are common. The neurobehavioral syndromes of MID are determined by the specific arteries involved and the location and extent of tissue infarction.     

Benzodiazepines: abuse and new use.

Both abuse and new uses for benzodiazepines are reviewed. The pharmacology of benzodiazepines is summarized and statistics regarding their general use are given. The question of benzodiazepine abuse is reviewed in some detail and the question of rebound, recurrence of symptoms and physiological withdrawal is differentiated. Benzodiazepines are regarded as a very safe class of drugs and the abuse potential is felt to be negligible provided that they are prescribed for appropriate conditions and monitored carefully. The dangers of alternatives to benzodiazepines such as alcohol or barbiturates is emphasized. New uses for benzodiazepines are reviewed including the use of benzodiazepines in panic disorder, as well as an adjunct in the therapy of mania and some psychotic states. Rational prescribing of benzodiazepines is encouraged and the attitude that these are dangerous and addictive drugs is discouraged and put into perspective.     

Structural modeling of functional neural pathways mapped with 2-deoxyglucose: effects of acoustic startle habituation on the auditory system

This paper describes the first application of structural modeling to neuroscience. Structural modeling (also known as path analysis) is a method to assess the relative impact of directional links in a system and how these interrelations may change under different conditions. The objective was to demonstrate how structural modeling can be used to determine the functional interrelationships between brain structures that form the auditory system. Using structural modeling, changes in auditory system 2-DG uptake were examined during long- and short-term habituation of the acoustic startle reflex. Models were based on the anatomical connections between central auditory system structures. Using functional 2-DG data, the correlations between these structures were calculated and numerical weights were computed for each anatomical link. The analysis revealed that the lemniscal path was dominant during short-term habituation, while during long-term habituation this influence was modified through extra-lemniscal pathways. The models are discussed in the context of previous findings to demonstrate how structural modeling can not only complement, but also extract more information from 2-DG mapping experiments.