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.

Protective effects of bezafibrate against elaidic acid-induced accumulation of lipid droplets in monocytic cells.

Some factors related to diet, such as trans fatty acids (TFA), are known to be involved in the progression of atherosclerosis in humans. Thus, the aim of our study was (i) to evaluate the effects of three dietary free fatty acids (FFA) (elaidic (EA), oleic (OA) and palmitic acid (PA)) on U937 human monocytes, and (ii) to study the eventual benefits of bezafibrate (BZF), a pan-agonist for PPAR isoforms (α, γ and δ) in U937 cells treated with FFA. Morphologic and functional changes were investigated by microscopic and flow cytometric methods. Cellular lipid content, lipid droplets and FA composition were identified and studied. All analyses were also realized in association with or without BZF. Contrary to OA and PA, EA slightly induced both propidium iodide-positive cells and mitochondrial depolarization. In addition, in contrast to OA and PA, EA induced only a slight increase in superoxide anion production. However, EA and OA promoted cytoplasmic lipid droplets accumulation. Only EA and OA significantly increased CD36 expression. It is noteworthy that BZF had a more or less pronounced protective effect against EA-, OA- and PA-induced side effects: BZF attenuated the impaired cell viability and inflammatory response, decreased superoxide anion production and prevented the accumulation of neutral and polar lipids. The effects were less pronounced with OA and PA than with EA. Altogether, our data revealed a benefit of BZF on the side effects induced especially with EA. It may thus be of interest in preventing the early stages of atherosclerotic plaque formation.

Teaching life-long learning skills in a fourth-year medical curriculum.

For more than twenty years, the Ruth Lilly Medical Library has been a traditional part of the Indiana University School of Medicine curriculum. Recently, following changes to the curriculum, the Library's role has evolved to include responsibility for developing and teaching a Medical Informatics rotation as part of the senior year clerkships. Heavy emphasis is placed on acquiring life-long learning skills, especially on locating and critically appraising the best clinical evidence in the medical literature. In its first four months, the rotation has been quite favorably received by both students and faculty, but will continue changing to keep pace with future curriculum alterations and new technology.

MD consult: one-stop Web-based clinical information.

MD Consult is the latest one-stop shop for clinical information. It has assembled MEDLINE, full-text journals and textbooks, clinical practice guidelines, patient information, and CME courses for the clinician in one location on the Web. This service is reviewed from the perspective of the clinician and for use at the reference desk. For the clinician, MD Consult is an authoritative, convenient, easy-to-use, and inexpensive service. For the librarian, it is important to become familiar with its features in order to form an opinion about the product. Features and pricing are discussed.

Current Contents on Diskette and Reference Update.

Both Current Contents on Diskette and Reference Update provide an excellent mechanism for keeping abreast of the biomedical literature with a personal computer. Both systems are compatible with the two major database management programs for manipulating reprint files. Reference Update exports directly to Reference Manager (a choice on the main menu). Exporting to a file can also be done with one of four formats: Table of Contents, MEDLINE, Full, and One Line. To export Reference Update records into Pro-Cite, for example, the records must first be downloaded into MEDLINE format. Current Contents on Diskette also exports in four different formats: MEDLINE, Comma Delimited, Screen Image, and DIALOG. MEDLINE corresponds to Reference Manager format, and Comma Delimited corresponds to Pro-Cite format. Both products include reprint request systems that can be used directly from the programs. The two products share many features and differ primarily in terms of journal coverage. Current Contents on Diskette provides document delivery by means of the Genuine Article service, and Reference Update offers a synonym feature. Both programs are attractive alternatives to manual or on-line searching of the biomedical literature.

The effect of CD-ROM MEDLINE on online end-user and mediated searching: a follow-up study.

Indiana University School of Medicine Library (IUSML) has traditionally been a high volume searching institution. The dramatic effect of CD-ROM on online end-user searching and the negligible effect on mediated searching was reported in an earlier study. This follow-up study reveals that the proportion of mediated searching has been drastically reduced from 94% in 1986/87 to 39% as of November 1989. Mediated searches are declining in absolute numbers as well. End-user searching, by contrast, has increased by 54% percent over the previous year. A related trend is the increased use of CD-ROM by the librarian as an alternative to mediated online searching. These trends are expected to continue as IUSML expands its CD-ROM operation to include other databases. As mediated searching declines, the librarian's role will increasingly include end-user training.

CD Plus: MEDLINE on CD-ROM.

Developed by CD Plus (formerly Online Research Systems, Inc.), CD Plus MEDLINE is a welcome addition to the growing number of MEDLINE CD-ROM products. CD Plus MEDLINE offers monthly updates and coverage of the full MEDLINE database back to 1966. Some of its features include mapping to MeSH, explode capability, permuted term index, scope notes from the Annotated MeSH, and access to the tree structures. The system is designed for the novice as well as the professional searcher. The article takes a descriptive look at MEDLINE on CD Plus, its software, searching capabilities, limitations, special features, and system requirements.

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.

The effect of CD-ROM MEDLINE on online end user and mediated searching.

Since 1970, Indiana University School of Medicine Library (IUSML) has traditionally been a high volume online searching institution. The library recently implemented an end user searching program which includes MEDLINE on CD-ROM. The effect of CD-ROM on online end user and mediated searching is discussed. Comparative statistics are provided by category of search service. CD-ROM has had a dramatic lowering effect on online end user searching and has had little effect on mediated searching. IUSML's experience with CD-ROM technology has been a positive one. Trained end users have become IUSML's greatest asset.