Attenuation of 7-ketocholesterol- and 7ß-hydroxycholesterol-induced oxiapoptophagy by nutrients, synthetic molecules and oils: Potential for the prevention of age-related diseases.

Age-related diseases for which there are no effective treatments include cardiovascular diseases; neurodegenerative diseases such as Alzheimer's disease; eye disorders such as cataract and age-related macular degeneration; and, more recently, Severe Acute Respiratory Syndrome (SARS-CoV-2). These diseases are associated with plasma and/or tissue increases in cholesterol derivatives mainly formed by auto-oxidation: 7-ketocholesterol, also known as 7-oxo-cholesterol, and 7ß-hydroxycholesterol. The formation of these oxysterols can be considered as a consequence of mitochondrial and peroxisomal dysfunction, leading to increased in oxidative stress, which is accentuated with age. 7-ketocholesterol and 7ß-hydroxycholesterol cause a specific form of cytotoxic activity defined as oxiapoptophagy, including oxidative stress and induction of death by apoptosis associated with autophagic criteria. Oxiaptophagy is associated with organelle dysfunction and in particular with mitochondrial and peroxisomal alterations involved in the induction of cell death and in the rupture of redox balance. As the criteria characterizing 7-ketocholesterol- and 7ß-hydroxycholesterol-induced cytotoxicity are often simultaneously observed in major age-related diseases (cardiovascular diseases, age-related macular degeneration, Alzheimer's disease) the involvement of these oxysterols in the pathophysiology of the latter seems increasingly likely. It is therefore important to better understand the signalling pathways associated with the toxicity of 7-ketocholesterol and 7ß-hydroxycholesterol in order to identify pharmacological targets, nutrients and synthetic molecules attenuating or inhibiting the cytotoxic activities of these oxysterols. Numerous natural cytoprotective compounds have been identified: vitamins, fatty acids, polyphenols, terpenes, vegetal pigments, antioxidants, mixtures of compounds (oils, plant extracts) and bacterial enzymes. However, few synthetic molecules are able to prevent 7-ketocholesterol- and/or 7ß-hydroxycholesterol-induced cytotoxicity: dimethyl fumarate, monomethyl fumarate, the tyrosine kinase inhibitor AG126, memantine, simvastatine, Trolox, dimethylsufoxide, mangafodipir and mitochondrial permeability transition pore (MPTP) inhibitors. The effectiveness of these compounds, several of which are already in use in humans, makes it possible to consider using them for the treatment of certain age-related diseases associated with increased plasma and/or tissue levels of 7-ketocholesterol and/or 7ß-hydroxycholesterol.

MEDLINE, cancer-CD, SCI-CD addition on CD-ROM.

Compact Disc Read-Only-Memory, CD-ROM, is a powerful resource which combines the best features of both online and print access to the literature: multiple access points and leisurely browsing (online accessibility without a modem or without its cost). Applied to the MEDLINE database, this technology has created a brand new market, one which is increasingly competitive and therefore evolving rapidly. Five MEDLINE and two non-MEDLINE products are reviewed. The MEDLINE products include: BRS/COLLEAGUE DISC, Compact Cambridge, Ebsco's Core MEDLINE, Online Research System's Compact Med-Base, and SilverPlatter's MEDLINE on CD-ROM. The two other products include: Institute for Scientific Information's SCI CD Edition and SilverPlatter's CANCER-CD. The market is still wide open and the buyer is wise to try before he buys. However, there are great differences between the various packagings of a rather familiar product. In our view, in terms of ease of use, SilverPlatter was the clear winner. Ebsco's product is attractive because of its containment on one CD. Med-Base is the most original and offers special features not found elsewhere. Finally, personal preference is a strong consideration and should not be overlooked.

Subject searching of monographs online in the medical literature.

Searching by subject for monographic information online in the medical literature is a challenging task. The NLM database of choice is CATLINE. Other NLM databases of interest are BIOTHICSLINE, CANCERLIT, HEALTH, POPLINE, and TOXLINE. Ten BRS databases are also discussed. Of these, Books in Print, Bookinfo, and OCLC are explored further. The databases are compared as to number of total records and number and percentage of monographs. Three topics were searched on CROSS to compare hits on BBIP, BOOK, and OCLC. The same searches were run on CATLINE. The parameters of time coverage and language were equalized and the resulting citations were compared and analyzed for duplication and uniqueness. With the input of CATLINE tapes into OCLC, OCLC has become the database of choice for searching by subject for medical monographs.