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)

For proper use of systemic GCS, a basic knowledge of the normal HPA axis, as well as knowledge of the pharmacology, clinical usage guidelines, and adverse reactions of these agents is imperative. Both short-term (acute) and long-term side effects should be well known by the physician. The pros and cons of oral and parenteral therapy for various disorders and in various situations should be recognized. For long-term therapy, an intermediate-acting agent such as prednisone in single, early morning doses is most commonly used to minimize suppression of the HPA axis. Alternate-morning doses produce even less suppression if the disease process will respond. A through patient history, including general medical history and medications the patient is taking, is important to anticipate any potential problems. Weight and blood pressure should be checked initially and every 1 to 3 months thereafter. Blood glucose, electrolytes, and lipid studies, including triglycerides, should be done approximately every 6 months. An ophthalmology examination should be performed every year, and stool examination for occult blood and chest radiography can be obtained as indicated. Bone density studies might be necessary in patients who are at high risk for osteoporosis. Specific acute situations may dictate other studies. The patient on long-term GCS should be kept as active as possible, as mild-to-moderate exercise helps prevent certain side effects, such as osteoporosis. The dose of oral GCS is best given with food to prevent gastrointestinal irritation, and agents to decrease gastric acidity might be needed in certain situations. Exposure to infections should be prevented, where possible, and treatment initiated at the first sign of systemic or cutaneous infection. Pain should be evaluated early, especially abdominal pain or bone pain; MRI is indicated if aseptic necrosis of bone is suspected. Both trauma and severe sun exposure should be avoided. Consultation with other specialists is strongly recommended when the situation dictates. Diet is one of the most important strategies to minimize side effects from long-term GCS therapy. Vegetable protein should be increased in the diet, and fats and carbohydrates limited. Adequate calcium is imperative, and calcium supplementation is recommended for high-risk osteoporosis patients. Small amounts of vitamin D may be necessary to increase absorption of calcium. Restriction of sodium is also important, as is maintainance of dietary potassium. Supplemental potassium may be necessary in some patients, and a thiazide diuretic might be useful in patients with hypertension, edema, or osteoporosis. Vitamin C can be given to promote wound healing. A good doctor-patient relationship is important in managing the patient on long-term GCS. The patient must return for regular visits and be encouraged to promptly report any adverse reactions to the physician. If these criteria are maintained and the strategies noted previously are followed, problems from long-term therapy with GCS will be minimized.
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PMID:Minimizing complications from systemic glucocorticosteroid use. 878 96

Recently, the HPA-1b (PlA2) polymorphism of the platelet glycoprotein IIIa has been suggested as a genetic risk factor for coronary artery disease. We conducted two case-control studies of 103 patients with ischaemic cerebrovascular disease (CVD) and 101 patients with ischaemic heart disease (IHD). The groups were matched for age, race and sex. No significant differences regarding selected risk factors (hypertension, diabetes mellitus, hypercholesterolaemia and smoking) were found between case patients and controls. Moreover, we investigated 286 normal individuals from the Mediterranean area. Genotyping of HPA-1 was performed by PCR-allelic specific restriction and single-strand conformation polymorphism analysis. The prevalence of HPA-1b was similar among case patients and controls (29.2% vs. 25.3% and 26.7% vs. 34.6% for CVD and IHD case-control studies, respectively). The HPA-1b allele was found in 36.4% of the normal population. Finally, the analysis of platelet function in nine controls with the three possible HPA-1 genotypes (three a/a, three a/b and three b/b) indicates that HPA-1b genotype does not modify either the in vitro platelet aggregation and activation profile, nor the GP IIb/IIIa interaction with fibrinogen or von Willebrand factor. Our results do not support the role of HPA-1b polymorphism as an inherited risk factor for arterial thrombotic disease.
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PMID:HPA-1 genotype in arterial thrombosis--role of HPA-1b polymorphism in platelet function. 928 92

Recently, we have demonstrated that human platelet antigen 1b (HPA-1b or P1A2) is a hereditary risk factor for platelet thrombogenicity leading to premature myocardial infarction in preexisting coronary artery disease. However, HPA-lb does not represent a risk factor for coronary artery disease itself. The aim of our present study was to evaluate the role of HPA-lb on the outcome in patients after coronary-artery bypass surgery. We prospectively determined the HPA-1 genotype in 261 consecutive patients prior to saphenous-vein coronary-artery bypass grafting. The patients were followed for one year. Among patients with bypass occlusion, myocardial infarction, or death more than 30 days after surgery, the prevalence of HPA-lb was significantly higher than among patients without postoperative complications (60 percent, 6/10, vs. 24 percent, 58/241, p <0.05, odds ratio 4.7). Using a stepwise logistic regression analysis with the variables HPA-1b, age, sex, body mass index, smoking (pack-years), hypertension, diabetes, cholesterol and triglyceride concentration, only HPA-lb had a significant association with bypass occlusion, myocardial infarction, or death after bypass surgery (p = 0.019, odds ratio 4.7). This study shows that HPA-1b is a hereditary risk factor for bypass occlusion, myocardial infarction, or death in patients after coronary-artery bypass surgery.
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PMID:Prospective analysis after coronary-artery bypass grafting: platelet GP IIIa polymorphism (HPA-1b/PIA2) is a risk factor for bypass occlusion, myocardial infarction, and death. 1074 44

Normal ageing and Alzheimer's disease (AD) have many features in common and, in many respects, both conditions only differ by quantitative criteria. A variety of genetic, medical and environmental factors modulate the ageing-related processes leading the brain into the devastation of AD. In accordance with the concept that AD is a metabolic disease, these risk factors deteriorate the homeostasis of the Ca(2+)-energy-redox triangle and disrupt the cerebral reserve capacity under metabolic stress. The major genetic risk factors (APP and presenilin mutations, Down's syndrome, apolipoprotein E4) are associated with a compromise of the homeostatic triangle. The pathophysiological processes leading to this vulnerability remain elusive at present, while mitochondrial mutations can be plausibly integrated into the metabolic scenario. The metabolic leitmotif is particularly evident with medical risk factors which are associated with an impaired cerebral perfusion, such as cerebrovascular diseases including stroke, cardiovascular diseases, hypo- and hypertension. Traumatic brain injury represents another example due to the persistent metabolic stress following the acute event. Thyroid diseases have detrimental sequela for cerebral metabolism as well. Furthermore, major depression and presumably chronic stress endanger susceptible brain areas mediated by a host of hormonal imbalances, particularly the HPA-axis dysregulation. Sociocultural and lifestyle factors like education, physical activity, diet and smoking may also modulate the individual risk affecting both reserve capacity and vulnerability. The pathophysiological relevance of trace metals, including aluminum and iron, is highly controversial; at any rate, they may adversely affect cellular defences, antioxidant competence in particular. The relative contribution of these factors, however, is as individual as the pattern of the factors. In familial AD, the genetic factors clearly drive the sequence of events. A strong interaction of fat metabolism and apoE polymorphism is suggested by intercultural epidemiological findings. In cultures, less plagued by the 'blessings' of the 'cafeteria diet-sedentary' Western lifestyle, apoE4 appears to be not a risk factor for AD. This intriguing evidence suggests that, analogous to cardiovascular diseases, apoE4 requires a hyperlipidaemic lifestyle to manifest as AD risk factor. Overall, the etiology of AD is a key paradigm for a gene-environment interaction. Copyright 2000 John Wiley & Sons, Ltd.
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PMID:A unifying hypothesis of Alzheimer's disease. III. Risk factors. 1240 43

Initial research on the functional significance of two novel hypothalamic neuropeptides, orexin-A and orexin-B, suggested an important role in appetite regulation. Since then, however, these peptides have also been shown to influence a wide range of other physiological and behavioural processes. In this paper, we review the now quite extensive literature on orexins and appetite control, and consider their additional effects within this context. Although the evidence for orexin (particularly orexin-A and the orexin-1 receptor) involvement in many aspects of ingestive physiology and behaviour is incontrovertible, central administration of orexins is also associated with increased EEG arousal and wakefulness, locomotor activity and grooming, sympathetic and HPA activity, and pain thresholds. Since the orexin system is selectively activated by signals indicating severe nutritional depletion, it would be highly adaptive for a hungry animal not only to seek sustenance but also to remain fully alert to dangers in the environment. Crucial evidence indicates that orexin-A increases food intake by delaying the onset of a behaviourally normal satiety sequence. In contrast, a selective orexin-1 receptor antagonist (SB-334867) suppresses food intake and advances the onset of a normal satiety sequence. These data suggest that orexin-1 receptors mediate the episodic signalling of satiety and appear to bridge the transition from eating to resting in the rats' feeding-sleep cycle. The argument is developed that the diverse physiological and behavioural effects of orexins can best be understood in terms of an integrated set of reactions which function to rectify nutritional status without compromising personal survival. Indeed, many of the non-ingestive effects of orexin administration are identical to the cluster of active defences mediated via the lateral and dorsolateral columns of the midbrain periaqueductal gray matter, i.e., somatomotor activation, vigilance, tachycardia, hypertension and non-opioid analgesia. In our view, therefore, the LH orexin system is very well placed to orchestrate the diverse subsystems involved in foraging under potentially dangerous circumstances, i.e., finding and ingesting food without oneself becoming a meal for someone else.
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PMID:Orexins and appetite regulation. 1245 Jul 37

The auditory system is permanently open - even during sleep. Its quick and overshooting excitations caused by noise signals are subcortically connected via the amygdala to the hypothalamic-pituitary-adrenal-axis (HPA-axis). Thus noise causes the release of different stress hormones (e.g. corticotropin releasing hormone: CRH; adrenocorticotropic hormone: ACTH) especially in sleeping persons during the vagotropic night/early morning phase. These effects occur below the waking threshold of noise and are mainly without mental control. Animal experiments show noise-induced changes in sensitivity of cellular cortisol receptors by increase of heat-shock proteins, and ultrastructural changes in the tissue of the heart and the adrenal gland. Increased cortisol levels have been found in humans when exposed to aircraft noise or road traffic noise during sleep. The effects of longer-lasting activation of the HPA-axis, especially long term increase of cortisol, are manifold: immuno suppression (e.g. eosinopenia), insulin resistance (e.g. diabetes), cardiovascular diseases (e.g. hypertension and arteriosclerosis), catabolism (e.g. ostoeporosis), intestinal problems (e.g. stress ulcer) etc. Even worse may be the widespread extrahypothalamical effects of CRH/and/or ACTH which have the potential to influence nearly all regulatory systems, causing for example stress-dysmenorrhea etc. as signs of disturbed hormonal balance.
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PMID:Possible health effects of noise induced cortisol increase. 1268 72

Visceral obesity represents an important risk factor associated with hypertension, diabetes and cardiovascular diseases. Since this condition is associated with a disruption of the functioning of the HPA axis, stress-induced HPA axis activation has been identified to play an important role in this preferential body fat accumulation. HPA axis activation increases cortisol (corticosterone) production which has been shown to exert hyperphagic and antithermogenic effects. Since abdominal adipose tissue has more cells per mass units, higher blood flow and more glucocorticoid receptors, glucocorticoids affect abdominal fat to a greater extent than subcutaneous adipose tissue. Cushing's syndrome in humans is the best evidence showing a link between hypercortisolemia and accumulation of central fat. The Hervey's hypothesis which suggests that fat cells take up and catabolize glucocorticoids is one of the possible regulatory effect that supports the adaptive role of visceral fat in response to stress. This is also supported by other evidence showing that abdominal obesity is associated with an increased cortisol clearance. Hormonal and enzymatic changes have been implicated in this preferential body fat accumulation in response to stress. Specific genetic background may also accentuate this visceral fat accumulation in some individuals exposed to stress. Alternatively, obesity could also be a source of stress promoting the visceral fat accumulation since visceral fat is able to release cytokines which stimulate the HPA axis. Even if the available literature does not permit to establish clearly which comes first, it suggests that visceral obesity could represent a non optimal physiological adaptation to stress. In this context, visceral obesity treatment should focus on stress management and weight loss strategies in order to stop this vicious circle.
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PMID:Is visceral obesity a physiological adaptation to stress? 1461 17

Prolonged exposure to stress and the resulting over-stimulation of the HPA system are often detrimental to the homeostasis of an organism. In fact, chronic stress is believed to affect the pathology of several disease states including coronary heart disease and hypertension, diabetes and obesity. In humans, mutations in the GLC1A gene have been associated with primary open angle glaucoma. Previous studies on this gene have suggested that its expression is also affected by the same factors that mediate the stress response. With the ultimate goal of using the nematode, Caenorhabditis elegans, as an invertebrate model for glaucoma, we have measured the stress responsiveness of the cof-2 gene, one of two C. elegans proteins with significant homology to the myocilin olfactomedin domain. We show that both cof-2 mRNA and protein expression are developmentally regulated and that both are affected by heat shock stress.
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PMID:Glaucoma studies in the eyeless worm: stress responsiveness and temporal expression of the Caenorhabditis elegans myocilin-like gene, cof-2. 1564 Nov 63

This study was performed to investigate the expression of the major isoforms of nitric oxide synthase mRNA and protein in the hypothalamo-pituitary-adrenal axis (HPA axis) of spontaneously hypertensive rats (SHR) at two different postnatal ages corresponding to the development of genetic hypertension. Using RT-PCR and Western blot techniques, the mRNA and protein levels of neuronal (nNOS), endothelial (eNOS) and inducible (iNOS) isoforms were measured in 3- to 4-week-old (prehypertensive phase) and 12- to 13-week-old (established hypertension phase) SHR and age-matched normotensive Wistar-Kyoto (WKY) rats. nNOS but not eNOS mRNA levels were increased at prehypertensive and hypertensive phases in SHR HPA axis. Compared to age-matched WKY rats, significantly higher levels of nNOS protein were found in the hypothalamus, lower levels in the adrenal glands and no changes were observed in the pituitary gland. At both ages tested, there was no significant change in eNOS protein expression in SHR HPA axis. The expression of iNOS mRNA and protein was under detection limit. In the HPA axis, the expression of nNOS isoform appears to be differentially controlled at the transcriptional and translational levels in SHR. Increased mRNA levels and differential nNOS protein expression from birth in SHR HPA axis may contribute in the pathogenesis of genetic hypertension.
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PMID:Expression of nitric oxide synthase isoforms in hypothalamo-pituitary-adrenal axis during the development of spontaneous hypertension in rats. 1591 38

Conflicting results of an association of the human platelet antigen 1b (HPA-1b/PlA2), localized on the beta-subunit of the integrin alpha(IIb)beta3, and the alpha(2)807TT genotype of the integrin alpha2beta1 with coronary atherosclerosis and myocardial infarction have been reported. Both platelet receptor polymorphisms were genotyped in 3261 patients who had undergone coronary angiography, including 1175 survivors of a myocardial infarction, 1211 individuals with coronary artery disease but no history of myocardial infarction, and 571 control patients without angiographic coronary artery disease, and in 793 blood donors. In a case-control design, the prevalence of HPA-1b and alpha(2)807TT genotypes did not differ significantly between the patient groups with coronary artery disease or myocardial infarction and patient controls or blood donors. By contrast, using a multivariate case-only design, it was found that the median age of onset of myocardial infarction was 5.2 years earlier (P = 0.006) in carriers of the HPA-1b allele and 6.3 years earlier (P = 0.006) in carriers of the alpha(2)807TT genotype in the 264 survivors of myocardial infarction of recent onset with one- or two-vessel coronary artery disease. A significant interaction with the conventional risk factors hypercholesterolemia, smoking, diabetes, hypertension, and hyperfibrinogenemia was excluded. Human platelet antigen 1b and alpha(2)807TT are associated with premature myocardial infarction but not with coronary artery disease, suggesting a role of distinct integrin genotypes for increased platelet thrombogenicity. This association requires confirmation in follow-up studies.
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PMID:Association of polymorphisms of platelet membrane integrins alpha IIb(beta)3 (HPA-1b/Pl) and alpha2(beta)1 (alpha807TT) with premature myocardial infarction. 1597 10


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