Editor’s note: Science Scan is a roundup of recently published biotechnology-relevant research.
Hot flashes (or politically correct “power surges”) are one annoying symptom that torments menopausal women. It’s marked by sudden vasodilation with a sensation of heat, usually around the face, neck and upper chest. More serious consequences of the female climacteric are cardiac disease and osteoporosis.
Decreased bone mass and increased risk of fractures are hallmarks of osteoporosis. A cross section of normal bone suggests a fine-grain sponge, whereas diminished osteoporotic structure resembles ragged, jagged Swiss cheese. Bone constantly undergoes alternating resorption and formation to maintain concentration of calcium and phosphate.
Calcium supplementation is used widely among postmenopausal women to prevent osteoporosis and fractures. Now a large-scale clinical trial reports that calcium intake also has beneficial effects on high-density lipoprotein (HDL) the “good” cholesterol.
The American Journal of Medicine, in its April 2002 issue, announces this seemingly unrelated finding in a paper titled “Effects of calcium supplementation on serum lipid concentrations in normal older women: A randomized controlled trial.” Its co-authors are in New Zealand at the University of Auckland department of medicine.
The researchers randomly assigned 111 postmenopausal women to receive 1 gram of calcium citrate daily, and another 112 controls to ingest a dummy pill. After 12 months, HDL cholesterol levels had increased more in the calcium cohort than in the placebo group. HDL’s ratio to low-density lipoprotein (LDL) the “bad” cholesterol had increased 17 percent in the calcium-ingesting women vs. a mere 4 percent increase in controls. This was largely due to a 7 percent HDL increase in the calcium cohort, compared with a 6 percent decline in LDL levels.
The co-authors made the point, “Increases in HDL cholesterol level of this magnitude may be associated with 20 percent to 30 percent reductions in the rates of cardiovascular events. Since atherosclerosis is the most common cause of death in postmenopausal women, the hypolipidemic effects of calcium could have greater effects on morbidity and mortality in these women than on osteoporosis.”
Their paper concluded: “Calcium citrate supplementation causes beneficial changes in circulating lipids in postmenopausal women. This suggests that a reappraisal of the indications for calcium supplementation is necessary, and that its cost-effectiveness may have been underestimated.”
When Bent Out Of Shape, Normally Benign Proteins Turn Toxic In Human Diseases Such As Alzheimer’s
Most proteins depend for their functions on precise, 3-dimensional folded structures. But two papers in Nature dated April 5, 2002, tell a different story. One is titled: “Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases.” Its co-authors coaxed normally harmless proteins, one from bacteria, the other from cattle, to take on new structural configurations. That made them toxic to cells in culture.
The companion Nature article bears the title: “Naturally secreted oligomers of amyloid b protein potently inhibit hippocampal long-term potentiation in vivo.” It reports that small clusters of amyloid beta molecules the misfolded protein that accumulates in much bigger clumps as senile plaques in the brains of Alzheimer’s patients lethally disrupt the synapses in rat brains.
Mice Pinch Hitting For Obscure Human Inherited Disease Model Hallmarks Of Aging In Old Folks
Trichothiodystrophy (TTD) is a congenital autosomal recessive disorder with brittle hair as its hallmark. This results from a low content of cysteine, a sulfur-containing amino acid. TTD sometimes features mental impairment and short stature. Dutch researchers generated transgenic mice carrying a point mutation found in TTD patients. The rodents displayed brittle bones, premature gray hair, osteoporosis, osteosclerosis, curvature of the spine, body wasting, infertility and shortened life span all classic signs of aging in mutant mice with excessively damaged DNA. This marked them as animal models for human aging.
A paper in Science released online April 11, 2002, carries the title: “Premature aging in mice deficient in DNA repair and transcription.” The TTD mutation, which enhances the DNA impairment, correlates with an increased sensitivity to oxidative DNA damage. The authors hypothesize that aging in the TTD mice is caused by unrepaired DNA impairment. This compromises transcription, causing functional inactivation of critical genes, leading ultimately to apoptosis.
Busybody Cell Receptor, CD44, Heals Inflamed Lungs In Knockout Mice, May Help Treat Asthma
CD44, a cell receptor, is a versatile transmembrane protein. It turns up on immune system thymocytes, T cells, precursor B cells, monocytes and neutrophils but that’s not all. CD44 is also present on central nervous system white matter, on fibroblasts and skeletal muscle. It helps lymphocytes bind to endothelial venules, and assists in cell adhesion.
CD 44 is essential for sweeping inflammatory cells out of damaged lung tissue, and allowing the tissue to heal, as it gets rid of extracellular matrix breakdown products. This finding is reported in Science dated April 5, 2002, under the title: “Resolution of lung inflammation by CD44.” Its authors report that CD44-deficient mice succumbed to unremitting inflammation following experimental noninfectious lung injury, while CD44-plus animals recovered in about two weeks. The co-authors suggest their findings may prove useful in therapies for asthma, pulmonary fibrosis and other types of lung inflammation.