Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the association of amyloid beta-protein precursor (APP) and platelet derived microparticles in 20 normal controls and 91 patients with various diseases causing a thrombotic tendency. Compared with the controls, the mean percentage of APP-positive microparticles was significantly greater in the patients with cerebral infarction (39.1 +/- 17.7%, p < 0.001), diabetes (31.1 +/- 12.6%, p < 0.001), and uremia (30.1 +/- 14.7%, p < 0.01), but not in those with hypertension (8.2 +/- 6.3%, p = NS). Sixteen patients with cerebral infarction, 20 with diabetes, and 11 with uremia had microparticles with very high APP levels. In normal controls, 7.2 +/- 3.7% of the microparticles were positive for P-selectin, while the percentage in cerebral infarction, diabetes, uremia, and hypertension was respectively 43.5 +/- 15.1%, 40.0 +/- 12.8%, 31.8 +/- 12.2%, and 11.6 +/- 7.3%. There was a significant correlation between P-selectin and APP positivity of microparticles. Our results suggest that microparticle APP may have a regulatory influence on coagulation abnormalities.
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PMID:Amyloid beta-protein precursor-rich platelet microparticles in thrombotic disease. 753 36

Differential diagnosis of dementing diseases is very important to rule in the so-called treatable dementia. The new DSM-IV criteria for dementia include memory disturbances and one or more of aphasia, apraxia, or frontal lobe dysfunctions as essentials. Alzheimer disease requires, in addition, slowly progressive course and ruling out other brain or systemic diseases. Vascular dementia requires focal neurological or neuroimaging signs. Other diseases which cause dementia include chronic subdural hematoma, infection and brain tumor. CT or MRI can readily diagnose them if suspected and they may be treated. Systemic diseases associated with treatable dementia include electrolyte disturbances, hypothyroidism, vitamin deficiency, alcohol or drug intoxication, syphilis and HIV infection. Prevention of dementia seems to be the future problem as we could prevent cerebrovascular diseases by treating hypertension.
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PMID:[Clinical aspects of dementia]. 875 26

Genetic and other defects leading to brain changes in Down syndrome, Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, Gaucher disease, hypertension and other disorders are rapidly being identified. If brain access were possible, new candidates for gene replacement therapy, antisense oligonucleotides, immune proteins or growth factors might be used for treating these disease (Lowenstein et al., 1994; Wielbo et al., 1995). Further, a number of drugs, peptides, antibodies and biological response modifiers have proven valuable in inhibiting malignant, infectious and other pathological processes in vitro, but are unlikely to be employed clinically because of their limited access to brain.
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PMID:Modulation of blood-brain barrier permeability. 886 35

A great deal of secondary, or covariable, information is often collected during the course of large-scale clinical trials. This information typically includes demographic and anthropometric data but often also includes more elaborate laboratory-based measures that might be used to screen for adverse reactions to the preventive agent or treatment being tested. This information can be and often is used to identify individuals or, more likely, subgroups of individuals who appear to respond better (or worse) to the compound of relevance. Such heterogeneity in response is to be expected, since the basic biological constitution of individuals differs widely and since it is well known from simple pharmacokinetic assays that such differences can affect drug responses. Since genes influence the biological constitution of individuals, it is easy to argue that genetic differences between individuals could explain differential responsiveness to certain drugs, as pharmacogeneticists have suggested for years. In this article, it is argued that by collecting relevant genetic data on participants in large-scale clinical trials as though these data merely provided additional covariables, one might not only be in a position to identify responders and nonresponders to the compound being tested but could also be in a position to address fundamental questions about the nature and pathogenesis of the disease for which the compound was designed. Although we exemplify this simple argument by referring to antihypertensive compounds and research, this reference is made merely for reasons of convenience, since there are numerous compounds designed expressly for the prevention and treatment of hypertension, but rather few for Alzheimer disease. It is hoped that by adopting some of the guidelines and principles outlined herein, better and more appropriate compounds for the prevention and treatment of Alzheimer disease will be tested and ultimately made available to the patients for whom they work best.
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PMID:The use of genetic information in large-scale clinical trials: applications to Alzheimer research. 887 85

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

Intracranial vasculitis, or primary angiitis of the central nervous system (PACNS), is an uncommon, often fatal disorder that frequently responds to aggressive immunosuppressive therapy. Magnetic resonance imaging (MRI), cerebral angiography, and brain biopsy are diagnostic modalities that vary in invasiveness and diagnostic accuracy. The purpose of this study was to determine whether certain clinical or radiologic features were predictive of a diagnostic biopsy. Thirty consecutive patients undergoing brain biopsy to "rule out vasculitis" were studied. Nine patients demonstrated granulomatous or lymphocytic vasculitis, 1 had lymphocytic vasculitis and encephalitis secondary to arbovirus infection, 5 had thickened vessels consistent with hypertensive changes, 5 had amyloid angiopathy and/or changes of Alzheimer disease, 5 demonstrated no pathologic abnormalities, and 1 each had acute infarct, vascular malformation, aneurysm, acellular fibrinoid necrosis, and demyelination. The spectrum of MRI and angiographic changes associated with PACNS were nonspecific, overlapping extensively with changes of chronic hypertension and amyloid deposition. The predictive values of brain biopsy (90-100%) were significantly higher than those of angiography (37-50%) or MRI (43-72%). In this study, morbidity associated with aggressive immunosuppression was significantly greater than that associated with cerebral angiography or brain biopsy. Thus, wedge biopsy of cortical and leptomeningeal tissues is central to the multi-disciplinary approach to a patient with clinical suspicion of PACNS.
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PMID:Diagnosis of intracranial vasculitis: a multi-disciplinary approach. 960 Jan 95

In the article we discuss the role of serotonin in maintaining homeostasis paying special attention to the endocrinological aspect of the matter. It has been proved that it contributes to hypothalamus and hypophysis secretion regulation and interferes with paracrine activity in digestive and reproductive system. It is also an important constituent of platelets and takes part in aggregation and coagulation. It is known to be an atherogenic factor and to act as a growth stimulator for blood cells. It can be produced in exceed amounts by neoplasm or be released by activated thrombocytes during stress or coagulation. The influence of this hormone on the most of regulation mechanisms seems obvious. Presence of many different receptors as well as their number in all the structures of mammalian body makes it possible to use a range of agonists and antagonists in research concerning psychiatric diseases (e.g. bulimia, anorexia, depression), Alzheimer disease, migraine, hypertension, carcinoid related syndrome, multiple endocrine neoplasms and pre-menstrual syndrome. The promising results enable to use some of the modifiers in their clinical treatment though more research is needed for fully satisfactory effects.
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PMID:[Serotonin--structure, activity and clinical significance]. 1009 81

Docosahexaenoic acid (DHA) is essential for the growth and functional development of the brain in infants. DHA is also required for maintenance of normal brain function in adults. The inclusion of plentiful DHA in the diet improves learning ability, whereas deficiencies of DHA are associated with deficits in learning. DHA is taken up by the brain in preference to other fatty acids. The turnover of DHA in the brain is very fast, more so than is generally realized. The visual acuity of healthy, full-term, formula-fed infants is increased when their formula includes DHA. During the last 50 years, many infants have been fed formula diets lacking DHA and other omega-3 fatty acids. DHA deficiencies are associated with foetal alcohol syndrome, attention deficit hyperactivity disorder, cystic fibrosis, phenylketonuria, unipolar depression, aggressive hostility, and adrenoleukodystrophy. Decreases in DHA in the brain are associated with cognitive decline during aging and with onset of sporadic Alzheimer disease. The leading cause of death in western nations is cardiovascular disease. Epidemiological studies have shown a strong correlation between fish consumption and reduction in sudden death from myocardial infarction. The reduction is approximately 50% with 200 mg day(-1)of DHA from fish. DHA is the active component in fish. Not only does fish oil reduce triglycerides in the blood and decrease thrombosis, but it also prevents cardiac arrhythmias. The association of DHA deficiency with depression is the reason for the robust positive correlation between depression and myocardial infarction. Patients with cardiovascular disease or Type II diabetes are often advised to adopt a low-fat diet with a high proportion of carbohydrate. A study with women shows that this type of diet increases plasma triglycerides and the severity of Type II diabetes and coronary heart disease. DHA is present in fatty fish (salmon, tuna, mackerel) and mother's milk. DHA is present at low levels in meat and eggs, but is not usually present in infant formulas. EPA, another long-chain n-3 fatty acid, is also present in fatty fish. The shorter chain n-3 fatty acid, alpha-linolenic acid, is not converted very well to DHA in man. These longchain n-3 fatty acids (also known as omega-3 fatty acids) are now becoming available in some foods, especially infant formula and eggs in Europe and Japan. Fish oil decreases the proliferation of tumour cells, whereas arachidonic acid, a longchain n-6 fatty acid, increases their proliferation. These opposite effects are also seen with inflammation, particularly with rheumatoid arthritis, and with asthma. DHA has a positive effect on diseases such as hypertension, arthritis, atherosclerosis, depression, adult-onset diabetes mellitus, myocardial infarction, thrombosis, and some cancers.
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PMID:Health benefits of docosahexaenoic acid (DHA) 1047 62

Vascular risk factors are normally associated with cerebrovascular disease, which may lead to vascular dementia (VaD). Several recent studies suggest that there is increased risk of developing Alzheimer disease when exposed to these same vascular risk factors. In addition to old age, hypertension, peripheral arterial disease, certain types of cardiovascular disorders, diabetes mellitus, and smoking are now considered risk factors for late-onset Alzheimer disease. In this review, we examine several vascular factors and peripheral vascular pathophysiology implicated in Alzheimer disease and suggest certain mechanisms that might promote the association of vascular factors and late-onset Alzheimer disease. We support the implication that prevention or management of peripheral vascular disease may prevent or delay the onset of Alzheimer disease or mixed dementia.
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PMID:Vascular factors and Alzheimer disease. 1060 89

Stroke is an important public health problem worldwide. Those at high risk of stroke may be at high risk of cognitive impairment and dementia after stroke. Modifiable cardiovascular risk factors in midlife including hypertension, alcohol use, cigarette smoking, and certain dietary factors may be important targets for prevention of vascular causes of cognitive impairment. These same types of factors may also be associated with Alzheimer disease. Better control of cardiovascular disease risk factors might lead to delay or prevention of vascular dementia and Alzheimer disease.
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PMID:Prevention of vascular dementia. 1060 92


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