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Increased risk of ischaemic heart disease mortality in elderly men using anxiolytics-hypnotics and analgesics Results of the 10-year follow-up of the prospective population study “Men born in 1914”, Malmö, Sweden (1996)

Merlo, J. ; Hedblad, B. ; Ögren, M. ; [et al.]

Springer

European journal of clinical pharmacology 49 (1996), S. 261-265

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ISSN: 1432-1041

Keywords: Key words Cardiovascular mortality ; Anxiolytics-hypnotics; pharmacoepidemiology ; adverse drug effect ; cohort study ; benzodiazepines ; analgesics

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Abstract. Objectives: An increased risk of all-cause and cardiovascular mortality in users of anxiolytic-hypnotic drugs (AHD) has been reported, and use of analgesics may be an additional factor. Therefore, we examined the association of AHD and analgesic use, alone and in combination, with all-cause and ischaemic heart disease (IHD) mortality. Methods: Multivariate 10-year survival analysis in a population based cohort of 500 men born in 1914. Relative risks (RR) were adjusted by relevant confounders (blood pressure, serum cholesterol, diabetes mellitus, smoking habit, high alcohol consumption, history of previous IHD, cancer, and other diseases). Results: The RR of both all-cause and IHD mortality were significantly increased among those using both AHD and analgesics compared to those who took neither of these drugs: RR = 1.8 for all-cause mortality, and RR = 2.7 for IHD mortality. Conclusion: Although the number of cases was small, warranting interpretative caution, the current study suggests that the combined use of AHD (mainly benzodiazepines) and analgesics seems to be associated with an increase in all-cause and IHD mortality in elderly men.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00226325

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Principles and pitfalls in designing site-directed peptide ligands (1993)

Edmundson, A. B. ; Harris, D. L. ; Fan, Z.-C. ; [et al.]

New York, NY : Wiley-Blackwell

Proteins: Structure, Function, and Genetics 16 (1993), S. 246-267

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ISSN: 0887-3585

Keywords: generic binding cavity ; ligand design ; site-filling peptides ; effects of pH on binding D- and L-enantiomers ; immunoglobulin light chain dimer ; Chemistry ; Biochemistry and Biotechnology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Medicine

Notes: An immunoglobulin light chain dimer with a large generic binding cavity was used as a host molecule for designing a series of peptide guest ligands. In a screening procedure peptides coupled to solid supports were systematically tested for binding activity by enzyme linked immunosorbent assays (ELISA). Key members of the binding series were synthesized in milligram quantities and diffused into crystals of the host molecule for X-ray analyses. These peptides were incrementally increased in size and affinity until they nearly filled the cavity. Progressive changes in binding patterns were mapped by comparisons of crystallo-graphically refined structures of 14 peptide-protein complexes at 2.7 Å resolution. These comparisons led to guidelines for ligand design and also suggested ways to modify previously established binding patterns. By manipulating equilibria involving histidine, for example, it was possible to abolish one important intramolecular interaction of the bound ligand and substitute another. These events triggered a change inconformation of the ligand from a compact to an extended form and a comprehensive change in the mode of binding to the protein. In dipeptides of histidine and proline, protonation of both imidazolium nitrogen atoms was used to program anend-to-end reversal of the direction in which the ligand was inserted into the binding cavity. Peptides cocrystallized with proteins produced complexes somewhat different in structure from those in which ligandswere diffused into preexisting crystals. In sucha large and malleable cavity, space utilization was thus different when a ligand was introduced before the imposition of crystal packing restraints. © 1993 Wiley-Liss, Inc.

Additional Material: 11 Ill.