Structural studies of an oligodeoxynucleotide containing a trimethylene interstrand cross-link in a 5'-(CpG) motif: model of a malondialdehyde cross-link.

Malondialdehyde (MDA), a known mutagen and suspected carcinogen, is a product of lipid peroxidation and byproduct of eicosanoid biosynthesis. MDA can react with DNA to generate potentially mutagenic adducts on adenine, cytosine, and particularly guanine. In addition, repair-dependent frame shift mutations in a GCGCGC region of Salmonella typhimurium hisD3052 have been attributed to formation of interstrand cross-links (Mukai, F. H. and Goldstein, B. D. Science 1976, 191, 868--869). The cross-linked species is unstable and has never been characterized but has been postulated to be a bis-imino linkage between N(2) positions of guanines. An analogous linkage has now been investigated as a stable surrogate using the self-complementary oligodeoxynucleotide sequence 5'-d(AGGCG*CCT)(2,) in which G* represents guanines linked via a trimethylene chain between N(2) positions. The solution structure, obtained by NMR spectroscopy and molecular dynamics using a simulated annealing protocol, revealed the cross-link only minimally distorts duplex structure in the region of the cross-link. The tether is accommodated by partially unwinding the duplex at the lesion site to produce a bulge and tipping the guanine residues; the two guanines and the tether attain a nearly planar conformation. This distortion did not result in significant bending of the DNA, a result which was confirmed by gel electrophoresis studies of multimers of a 21-mer duplex containing the cross-link.

Oral nutritional supplement use in elderly nursing home patients.

OBJECTIVES: To determine why elderly nursing home patients receive liquid oral protein supplements, what nutritional assessment is utilized, and whether there is evidence of effectiveness. DESIGN: Retrospective, case control study comparing patients over 65 years of age, at two nursing homes, who were served oral supplements (OS) at least twice daily (n = 56), with a random sample of non-supplemented, non-tube fed patients (n = 53). Comparisons included medical diagnoses, medications, morbidity and mortality, weight changes, laboratory test results, and functional and behavioral status. RESULTS: Nursing home patients were begun on OS (median time after admission = 2 months, range = 0-72 months) primarily because of weight loss (71%) and poor appetite (16%). Supplemented patients were below an age-adjusted body weight on admission, unlike controls, and continued to lose weight until OS were started. On OS, weight was slowly regained over 9-10 months in a majority of patients to approximate admission weight. Some patients on OS showed improvement in albumin, total lymphocyte count, cholesterol, or hemoglobin, but too few patients had sufficient lab tests to verify any consistent effect. Mortality was higher in OS patients (8 vs 2, P = 0.057), who were also somewhat older (87.9 vs 84.5 years), but there was no statistical difference in infection or hospitalization rate. MEASUREMENTS: Nutritional assessment in these nursing homes consisted almost exclusively of (1) serial measurement of weight, (2) comparison of weight to (a) "ideal body weight" and (b) previous weight, and (3) a subjective evaluation of food consumption. No other anthropometric evaluations or laboratory tests were conducted for nutritional assessment. CONCLUSIONS: The diagnosis of and intervention in under-nutrition in nursing home patients is frequently disorganized. In addition, nutritional assessment, either for screening or for following intervention, is hampered by the lack of convenient and unambiguous assessment tools. OS use is associated with weight gain in many nursing home patients and also improves other nutritional parameters in selected individuals.