Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In elderly patients, aortic stiffness is a major determinant of increased end-systolic stress leading to left ventricular (LV) hypertrophy with impaired cardiac performance. However, in a rat model of aortic elastocalcinosis (induced by vitamin D(3)-nicotine [VDN] treatment), brief exposure (1 month) to increased aortic stiffness modified neither cardiac function nor cardiac structure. Here we report the impact of longer exposure (3 months) to aortic stiffness. Three months after induction of aortic stiffness, aortic characteristic impedance was measured in awake rats, 8 control and 10 VDN. Stroke volume was measured (electromagnetic probe) at baseline and after acute volume overload. LV weight/body weight ratio, collagen, and myosin heavy chain (MHC) contents were determined. Although aortic characteristic impedance increased (controls, 32+/-2; VDN rats, 50+/-8 10(3) dyne. s/cm(5); P=0.0248), stroke volume was maintained in VDN rats at baseline (controls, 223+/-18; VDN, 211+/-13 microL) and after volume overload (controls, 378+/-14; VDN, 338+/-15 microL). However, LV weight/body weight ratio (controls, 1.54+/-0.07; VDN, 1.73+/-0.05 g/kg; P=0.0397) and LV collagen content (controls, 31+/-4; VDN, 52+/-4 microgram/g dry wt; P=0.0192) increased. A shift from alpha-MHC (controls, 82+/-2%; VDN, 69+/-3%; P=0.0056) to beta-MHC (controls, 18+/-2%; VDN, 31+/-3%; P=0. 0056) was also observed. Three months' exposure to increased aortic stiffness in VDN rats induced LV hypertrophy with moderate interstitial fibrosis and a shift in the MHC-isoform pattern. Such structural adaptation maintains LV performance.
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PMID:Cardiac consequences of prolonged exposure to an isolated increase in aortic stiffness. 1040 25

The proper treatment of younger patients who have suffered ischemic stroke and who have no stroke risk factors other than antiphospholipid antibodies is unsettled. We propose a rationale to support adding dietary supplementation with calcium and vitamin D to the present standard regimen of anticoagulant therapy for these patients. We expect that the benefits from this additional therapy will prove additive. Proving this hypothesis will require large numbers of patients unlikely to present to any one center. The military health care system is well suited to such a study.
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PMID:Antiphospholipid antibodies, ischemic stroke in young adults, and calcium supplementation: a hypothesis. 1087 Mar 70

Diet and physical activity are two major lifestyle factors that play a role in the prevention or management of debilitating conditions affecting older people. Both under- and overnutrition predispose to diseases. Low sodium and high potassium intakes, as well as the consumption of fruits and vegetables are associated with a reduction of hypertension and diseases arising from hypertension such as stroke and dementia. Dietary patterns (consumption of quantity and types of fats, cholesterol, vegetable oils, fish) are important in the prevention of coronary heart disease. Calcium and vitamin D intakes are important factors in the development of osteoporosis, while various dietary factors have been linked to the development of cancer. Physical activity is important in the prevention of functional decline and increased survival, reduced incidence of falls and fractures, and has various cardiovascular health benefits. Apart from prevention of diseases, exercise also has an important role in improving function in some chronic diseases such as heart failure or chronic obstructive pulmonary disease. Both diet and exercise interact, so that public health recommendations often take the form of lifestyle modification advice in the prevention of disease and disability.
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PMID:Relationships among diet, physical activity and other lifestyle factors and debilitating diseases in the elderly. 1104 Oct 86

Although vitamin D hormone (VDH; 1,25-dihydroxyvitamin D(3)), the active metabolite of vitamin D, is the major Ca(2+)-regulatory steroid hormone in the periphery, it is not known whether it also modulates Ca(2+) homeostasis in brain neurons. Recently, chronic treatment with VDH was reported to protect brain neurons in both aging and animal models of stroke. However, it is unclear whether those actions were attributable to direct effects on brain cells or indirect effects mediated via peripheral pathways. VDH modulates L-type voltage-sensitive Ca(2+) channels (L-VSCCs) in peripheral tissues, and an increase in L-VSCCs appears linked to both brain aging and neuronal vulnerability. Therefore, we tested the hypothesis that VDH has direct neuroprotective actions and, in parallel, targets L-VSCCs in hippocampal neurons. Primary rat hippocampal cultures, treated for several days with VDH, exhibited a U-shaped concentration-response curve for neuroprotection against excitotoxic insults: lower concentrations of VDH (1-100 nm) were protective, but higher, nonphysiological concentrations (500-1000 nm) were not. Parallel studies using patch-clamp techniques found a similar U-shaped curve in which L-VSCC current was reduced at lower VDH concentrations and increased at higher (500 nm) concentrations. Real-time PCR studies demonstrated that VDH monotonically downregulated mRNA expression for the alpha(1C) and alpha(1D) pore-forming subunits of L-VSCCs. However, 500 nm VDH also nonspecifically reduced a range of other mRNA species. Thus, these studies provide the first evidence of (1) direct neuroprotective actions of VDH at relatively low concentrations, and (2) selective downregulation of L-VSCC expression in brain neurons at the same, lower concentrations.
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PMID:Vitamin D hormone confers neuroprotection in parallel with downregulation of L-type calcium channel expression in hippocampal neurons. 1115 Mar 25

Vascular calcification is increasingly recognized as a significant contributor to cardiovascular morbidity and mortality as well as a biologically regulated process potentially subject to prevention and reversal. Both coronary and aortic calcification are common and influence plaque rupture, angioplasty and surgical complications, and compensatory enlargement. Aortic calcification increases aortic rigidity and contributes to cadiac ischemia, left ventricular hypertrophy, heart failure, and stroke. Calcification is also common in aortic valve leaflets further compounding adverse hemodynamic effects. Vascular calcification has often been attributed to "passive" crystallization. However, functional similarities between atherosclerotic lesions and bone contradict this view and indicate that it is no more "passive" than in embryonic bone formation or bone repair. Similarities include presence of all the major components of bone osteoid, bone regulatory factors, and subpopulations of artery wall cells that retain osteoblastic lineage potential. Several animal models for vascular calcification are available. Spontaneous vascular calcification occurs in null mice for matrix GLA protein (MGP), a small matrix protein of unknown function, and osteoprotegerin (OPG), known to modulate osteoclast differentiation. Vascular calcification may also be induced by feeding vitamin D and calcium or warfarin to normal animals, or by fat-feeding mice null for apoE or the LDL-receptor. Overall, regulation of vascular calcification is a growing field with surprising mechanisms and connections to other fields of biology.
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PMID:Regulatory mechanisms in vascular calcification. 1118 30

Cardiovascular disease is a major cause of morbidity and mortality. Epidemiological studies indicate fish eaters are less likely to die prematurely compared with non-fish eaters. The protective properties in fish are likely to be related to its concentration of omega 3 fatty acids, calcium, selenium, vitamin D, taurine and coenzyme Q10. A high consumption of fruits and vegetables has been shown to protect against stroke and coronary heart disease. The presence of vitamins and minerals, as well as the complex array of non-nutrient compounds, found in fruits and vegetables would play an important role in this protection.
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PMID:Candidate foods in the Asia-Pacific region for cardiovascular protection: fish, fruit and vegetables. 1171 Mar 53

Inappropriate activation of the renin-angiotensin system, which plays a central role in the regulation of blood pressure, electrolyte, and volume homeostasis, may represent a major risk factor for hypertension, heart attack, and stroke. Mounting evidence from clinical studies has demonstrated an inverse relationship between circulating vitamin D levels and the blood pressure and/or plasma renin activity, but the mechanism is not understood. We show here that renin expression and plasma angiotensin II production were increased severalfold in vitamin D receptor-null (VDR-null) mice, leading to hypertension, cardiac hypertrophy, and increased water intake. However, the salt- and volume-sensing mechanisms that control renin synthesis are still intact in the mutant mice. In wild-type mice, inhibition of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] synthesis also led to an increase in renin expression, whereas 1,25(OH)(2)D(3) injection led to renin suppression. We found that vitamin D regulation of renin expression was independent of calcium metabolism and that 1,25(OH)(2)D(3) markedly suppressed renin transcription by a VDR-mediated mechanism in cell cultures. Hence, 1,25(OH)(2)D(3) is a novel negative endocrine regulator of the renin-angiotensin system. Its apparent critical role in electrolytes, volume, and blood pressure homeostasis suggests that vitamin D analogues could help prevent or ameliorate hypertension.
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PMID:1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. 2436 72

Atherosclerosis is the principal cause of myocardial infarction, stroke, and peripheral vascular disease, accounting for nearly half of all mortality in developed countries. The excessive growth of vascular smooth muscle cells is an important component in the development of atherosclerotic lesion. The direct effect of calcitriol and vitamin D analogs on the VSMCs proliferation is not clear. In this study we have analysed if calcitriol, Paricalcitol (19-nor-1,25-dihydroxy-vitamin D2) and EB1089 (experimental analog used as anticancerous) modify proliferation and the expression of vitamin D receptor (VDR) gene that is regulated at the transcriptional level by itself in the VSMCs. VSMCs proliferation was analysed by BrdU incorporation and VDR gene expression using RT-PCR. VSMCs proliferation was stimulated when calcitriol was added to the culture. VSMCs proliferation was significantly lower with analogs at the same dose. With regard to the functional study, the expression of VDR gene was upregulated by calcitriol at a concentration of 100 nM. There were no changes in this expression with the analogs. In conclusion, calcitriol, do not modify VSMCs proliferation. Therefore, Paricalcitol could have a minor proliferating effect on the wall of vessels that vitamin D.
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PMID:[Differential effect of vitamin D analogues on the proliferation of vascular smooth muscle cells]. 1277 67

Osteoporosis is a major public health problem that will become increasingly important as our population ages. It leads to fractures that deeply affect the patients' quality of life. Osteoporosis is recognised as a leading factor in healthcare cost worldwide. For years, experts have recommended hormone replacement therapy (HRT), consisting of oestrogen with or without progestin, as the first-line therapy to prevent bone loss in postmenopausal women. Recently published randomised, controlled trials and well-designed meta-analyses confirm that HRT has both advantages and disadvantages. The advantages include prevention of osteoporotic fractures and colorectal cancer. The disadvantages are the resulting adverse effects such as coronary artery disease, stroke, thromboembolic events, breast cancer and cholecystitis. In the light of these findings, medical associations recommend against the routine use of oestrogen and progestin for the prevention of chronic conditions in postmenopausal women. HRT, administered for the prevention of fractures in all young postmenopausal women, would have an additional cost/year of life gained that is too expensive. However, this strategy seems to be cost-effective when young postmenopausal women at high risk for fractures are selected. Even if this strategy seems attractive, the adverse effects of HRT are not acceptable. This situation implies that other treatments must be found to prevent or treat osteoporosis. Among them, calcium and vitamin D were shown to be cost-saving in osteoporosis and even costs-effective in osteopoenia in young postmenopausal women.
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PMID:An economic analysis of hormone replacement therapy for the prevention of fracture in young postmenopausal women. 1294 77

We have previously reported the merits of chronopharmacological effect of 1-alpha(OH) vitamin D3 in aged stroke-prone spontaneously hypertensive rat (SHRSP), a model of osteoporosis [Eur. J. Pharmacol. 428 (2001) 283.]. In this study, the chronopharmacological effect of 22-oxacalcitriol, a newly developed active vitamin D3 analogue with less calcemic activity, was evaluated by a single and repeated dosing of the drug in aged SHRSP. Animals (7 months old) were kept in rooms with a 12-h light/dark cycle. Single (12.5 microg/kg, i.v.) and repeated (5 microg/kg, i.v. three times a week for 12 weeks) dosing of 22-oxacalcitriol or vehicle was given at either 2 h after lights on (2HALO) or 14 h after lights on (14HALO). The severity of adverse reactions such as the changes of body weight, hypercalcemia and hyperphosphatemia, was significantly mild when the drug was given at 14HALO. Especially, the increase of serum Ca concentration was not detected at 14HALO trial. Serum concentrations of total (protein-bound and unbound) 22-oxacalcitriol and albumin (a major binding protein of the drug) of the 2HALO and 14HALO trials did not significantly differ. The decrease of parathyroid hormone (PTH) concentration was greater in the 14HALO trial while the increase in urinary ratio of Ca to creatinine was greater in the 2HALO trial. The increase in bone density of both femurs at the end of the study was greater in the 14HALO trial. The suppression of urinary excretion of deoxypyridinoline, an index of bone resorption capacity of osteoclast, was greater in the 14HALO trial, which indicates that the efficacy of 22-oxacalcitriol for suppressing bone resorption might vary with the dosing time. This is the first study to show the dosing-time-dependent changes in the efficacy and toxicity of 22-oxacalcitriol in the animal model of osteoporosis. Chronopharmacological differences seem to be more prominent than those of other vitamin D analogues. To use 22-oxacalcitriol at an adequate timing might provide better efficacy and safety than other vitamin D3 analogues for the treatment of osteoporosis.
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PMID:Chronopharmacology of oxacalcitriol in rat model of osteoporosis. 1504 57


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