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 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article reviews recent advances in the effects of estrogen on bone and other body systems. The effect of estrogen use for the prevention of osteoporosis is no longer a matter of debate. Some issues are still discussed, however, especially with regard to the magnitude of its protection (especially for hip fracture), which would be dependent on the time at which estrogen therapy is initiated with respect to menopause as well as its total duration of use. The mechanisms of estrogen's action on bone also remains poorly understood. Controversy persists concerning the specific contribution of an indirect action through the modulation of calciotropic hormones and a direct action on bone cells in which estrogen receptors have been identified. Estrogens have been shown to reduce osteoclastogenesis by modulating the production of cytokines (interleukins, tumor necrosis factor) and transforming growth factor from bone marrow and bone cells. In addition to its effects on bone, a great number of observational studies have evaluated the relationship between estrogen use and coronary heart disease. The overall risk of coronary disease is estimated to be reduced by 50% in women who use estrogen replacement therapy. This reduction would be even greater in women with previous atherosclerosis. Moreover, recent data suggest that estrogen use could be associated with delayed onset and reduced risk for Alzheimer's disease. Overall, estrogen treatment in postmenopausal women has several proven benefits. Conversely, the potential risks of long-term estrogen therapy include a slightly increased risk of breast cancer, which would be associated with long-term use. Although the individual decision for a postmenopausal woman to start estrogen replacement therapy must take into account this risk:benefit ratio, current evidence suggests a clear advantage for estrogen's benefits over its risks.
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PMID:Effect of estrogens on bone and other systems and hormonal substitute treatment. 922 84

Mammalian cells take up extracellular material by a variety of different mechanisms that are collectively termed endocytosis. Endocytic mechanisms serve many important cellular functions including the uptake of extracellular nutrients, regulation of cell-surface receptor expression, maintenance of cell polarity, and antigen presentation. Endocytic pathways are also utilized by viruses, toxins, and symbiotic microorganisms to gain entry into cells. One of the best-characterized endocytic mechanisms is receptor-mediated endocytosis via clathrin-coated pits. This type of endocytosis constitutes the major emphasis of this review, with a brief discussion of other endocytic mechanisms and their comparison with the receptor-mediated pathway. This review describes and evaluates critically current understanding of the mechanisms of entry of plasma membrane components such as the receptor-ligand complexes and membrane lipids as well as the extracellular fluid into cells. The intracellular sorting and trafficking of these molecules upon internalization are also described. The roles of endocytosis in physiological and pathological processes are discussed. These include maintenance of cell polarization, antigen presentation, glucose transport, atherosclerosis, Alzheimer's disease, and the endocytosis of toxins and viruses.
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PMID:Endocytosis. 923 65

Reactive oxygen species (ROS) are produced by cellular metabolic reactions, and have been implicated in the pathogenesis of several diseases, including atherosclerosis, cancer, and Alzheimer's disease. Interestingly, clinical and epidemiologic studies have, in some cases, indicated that antioxidant nutrients may be effective in disease prevention. However, the efficacy of specific antioxidants in disease prevention is often both controversial and inconclusive. In an effort to elucidate the role of ROS and antioxidants in disease development and prevention, the chemistries of ROS and antioxidants have been examined extensively. Recently, molecular and cellular approaches have demonstrated that ROS and antioxidants can directly affect the cellular signaling apparatus and, consequently, the control of gene expression. This new research provides the link between ROS and antioxidant chemistries and the mechanisms of disease processes and prevention. This review illustrates how ROS function as potential intracellular and extracellular signaling molecules and how antioxidants can affect this process.
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PMID:Reactive oxygen species and antioxidants in signal transduction and gene expression. 935 79

Vascular dementia (VAD) is considered to be the second most common cause of dementia in Europe and the US. In Asia and many developing countries, it is more common than dementia of the Alzheimer's type (DAT). VAD is the most preventable form of dementia associated with later life. The pathogenesis of VAD is multifactorial, and it represents a heterogeneous, not a homogeneous, clinical entity. Classification of VAD by pathogenesis is important for its prevention and treatment. Control of the risk factors for VAD reduces its incidence and stabilises or improves cognitive performance following stroke. Proper diagnostic evaluation of VAD requires: (i) a well defined quantitative assessment of the cognitive deficits present; (ii) assessment of risk factors for stroke; (iii) identification of cerebral vascular lesions by history, neurological examination and neuroimaging; (iv) exclusion of other causes of dementia; (v) establishment of a positive diagnosis of possible, probable or definite VAD versus DAT or mixed VAD/DAT; and (vi) identification of the temporal relationship between cognitive deficits and cerebral vascular lesions. VAD can be subdivided into 8 major types, as follows: (i) multi-infarct dementia secondary to large cerebral emboli [type 1]; (ii) strategically placed infarctions causing dementia [type 2]; (iii) multiple subcortical lacunar lesions secondary to atherosclerosis or degenerative arteriolar changes [type 3]; (iv) Binswanger's disease (arteriosclerotic subcortical leukoencephalopathy) [type 4]; (v) mixtures of types 1, 2 and 3 [type 5]; (vi) haemorrhagic lesions causing dementia [type 6]; (vii) subcortical dementia secondary to hereditary factors (type 7); and (viii) mixtures of DAT and VAD (type 8). Treatment is dictated by the pathogenetic subtype of VAD that is present.
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PMID:Classification, diagnosis and treatment of vascular dementia. 935 23

The integrity of the cerebral vasculature is crucial to the maintenance of cognitive functions during ageing. Prevailing evidence suggests that cerebrovascular functions decline during normal ageing, with pronounced effects in Alzheimer's disease (AD). The causes of these changes largely remain unknown. While previous studies recorded ageing-related impairments, such as atherosclerosis and loss of innervation in basal surface arteries of the brain, it only recently has been realized that a number of subtle alterations in both the intracranial resistance vessels and the smaller capillaries is apparent in both ageing animals and humans. The dominant changes include alterations in composition of connective tissues and smooth muscle of large vessel walls, thickening of the vascular basement membrane, thinning of the endothelium in some species, loss of endothelial mitochondria and increased pericytes. Some of these attributes appear more affected in AD. Other abnormalities entail profound irregularities in the course of microvessels, unexplained inclusions in the basement membrane and changes in unique proteins and membrane lipids associated with the blood-brain barrier. Brain imaging and permeability studies show no clear functional evidence to support the structural and biochemical anomalies, but it is plausible that focal and transient breach of the blood-brain barrier in ageing, and more notably in AD, occurs. Thus, circumscribed neuronal populations in certain brain regions could become vulnerable. Furthermore, the characteristic deposition of amyloid in vessels in AD may exacerbate the decline in vascular function and promote chronic hypoperfusion. Although not explicit from current studies, it is likely that the brain vasculature is continually modified by growth and repair mechanisms in attempts to maintain perfusion during ageing and disease.
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PMID:Cerebral vessels in ageing and Alzheimer's disease. 936 75

The APOE gene is located on chromosome 19, and the three common alleles are designated epsilon2, epsilon3, and epsilon4. The epsilon4 allele is associated with increased plasma cholesterol, atherosclerosis and cardiovascular disease, Alzheimer's disease, and decreased longevity. The objective of the present study was to estimate the distribution of APOE alleles in the Greek population by DNA analysis. The material consisted of 216 voluntary, healthy Greek blood donors (146 males/70 females). The APOE allele frequencies were epsilon2: 5.3%, epsilon3: 88.2%, epsilon4: 6.5%. The epsilon4 allele frequency of 6.5% in the Greek population is, together with the frequency in the Chinese population, among the lowest in the world.
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PMID:Apolipoprotein E polymorphism in the Greek population. 938 26

A wide variety of anatomic and histological alterations are common in brains of aged individuals. However, identification of intrinsic aging changes--as distinct from changes resulting from cumulative environmental insult--is problematic. Some degree of neuronal and volume loss would appear to be inevitable, but recent studies have suggested that the magnitudes of such changes are much less than previously thought, and studies of dendritic complexity in cognitively intact individuals suggest continuing neuronal plasticity into the eighth decade. A number of vascular changes become more frequent with age, many attributable to systemic conditions such as hypertension and atherosclerosis. Age-associated vascular changes not clearly linked to such conditions include hyaline arteriosclerotic changes with formation of arterial tortuosities in small intracranial vessels and the radiographic changes in deep cerebral white matter known as "leukoaraiosis." Aging is accompanied by increases in glial cell activation, in oxidative damage to proteins and lipids, in irreversible protein glycation, and in damage to DNA, and such changes may underlie in part the age-associated increasing incidence of "degenerative" conditions such as Alzheimer disease and Parkinson disease. A small number of histological changes appear to be universal in aged human brains. These include increasing numbers of corpora amylacea within astrocytic processes near blood-brain or cerebrospinal fluid-brain interfaces, accumulation of the "aging" pigment lipofuscin in all brain regions, and appearance of Alzheimer-type neurofibrillary tangles (but not necessarily amyloid plaques) in mesial temporal structures.
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PMID:Aging-associated changes in human brain. 941 75

A sequence encoding a novel glutathione transferase, GST A4-4, has been identified in a human fetal brain cDNA library. The protein has been produced in Escherichia coli after optimization of the codon usage for high-level heterologous expression. The dimeric protein has a subunit molecular mass of 25704 Da based on the deduced amino acid composition. Human GST A4-4 is a member of the Alpha class but shows only 53% amino acid sequence identity with the major liver enzyme GST A1-1. High catalytic efficiency with 4-hydroxyalkenals and other cytotoxic and mutagenic products of radical reactions and lipid peroxidation is a significant feature of GST A4-4. The kcat/Km values for 4-hydroxynonenal and 4-hydroxydecenal are > 3 x 10(6) M-1. s-1, several orders of magnitude higher than the values for conventional GST substrates. 4-Hydroxynonenal and other reactive electrophiles produced by oxidative metabolism have been linked to aging, atherosclerosis, cataract formation, Parkinson's disease and Alzheimer's disease, as well as other degenerative human conditions, suggesting that human GST A4-4 fulfills an important protective role and that variations in its expression may have significant pathophysiological consequences.
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PMID:Human glutathione transferase A4-4: an alpha class enzyme with high catalytic efficiency in the conjugation of 4-hydroxynonenal and other genotoxic products of lipid peroxidation. 946 7

The function of the immune system declines with age. It is the aim of the present review to demonstrate that it makes sense to distinguish between primary and secondary alterations of immune reactivity in the elderly. Primary changes occur as the result of an age-dependent intrinsic decline of immune responsiveness. They also occur in healthy persons, i.e. persons selected according to the criteria of the SENIEUR protocol of the European Community's Concerted Action Program on Aging (EURAGE). T lymphocytes are hereby more severely affected than B cells or antigen presenting cells, possibly due to the involution of the thymus, which is almost complete at the age of 60. Secondary immunological changes occur as the result of environmental factors including diet, drug intake, physical activity etc. or are alternatively due to underlying diseases. In this article, the effects of high lipid intake as well as the impact of diseases, such as for instance Alzheimer's disease and atherosclerosis, will be addressed. The results underline the complexity of immunological alterations to be expected in old age. Changes in the aging immune system represent an opportunity for increased frequency and severity of disease and endanger the protective effect of vaccination.
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PMID:Primary and secondary alterations of immune reactivity in the elderly: impact of dietary factors and disease. 947 75

The idea of a fat transport system in the plasma of mammals evolved slowly over three centuries. At the turn of this century, it was discovered that plasma globulins contained lecithin and that the digestion of plasma proteins with pepsin liberated small amounts of fat and cholesterol. The high density lipoprotein (HDL) was first isolated from horse serum in 1929 and the low density lipoprotein (LDL) in 1950. It was then shown that flotation of plasma in the ultracentrifuge revealed an array of lipoproteins that included VLDL, LDL and HDL and permitted quantitation. Subsequently, it was discovered that the free fatty acids (FFA) in plasma were bound to albumin and varied with feeding and fasting. From further studies, it was concluded that lipoprotein-bound triglycerides were delivered to adipose cells for uptake after meals; during fasting, the fat cells secreted FFA, which provided fuel for many tissues. The protein components of the lipoproteins (apopeptides) were characterized in the period from 1960 to 1970 and the LDL-receptor was identified in 1974. Fat transport was then established as a receptor-mediated delivery system of lipoproteins to targeted tissues. Defects in this system due to genetically altered or absent receptors explained dyslipidemias, which promoted atherosclerosis, xanthomatosis and Alzheimer's disease.
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PMID:Discovery of the lipoproteins, their role in fat transport and their significance as risk factors. 947 44


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