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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cellular phenotype is the result of a dynamic interaction between a cell's intrinsic genetic program and the morphogenetic signals that serve to modulate the extent to which that program is expressed. In the present study we have examined how morphogenetic information might be stored in the extracellular matrix (ECM) and communicated to the neonatal heart cell (NHC) by the cardiac alpha 1 beta 1 integrin molecule. A thin film of type I collagen (T1C) was prepared with a defined orientation. This was achieved by applying T1C to the peripheral edge of a 100 mm culture dish. The T1C was then drawn across the surface of the dish in a continuous stroke with a sterile cell scraper and allowed to polymerize. When NHCs were cultured on this substrate, they spread, as a population, along a common axis in parallel with the gel lattice and expressed an in vivo-like phenotype. Individual NHCs displayed an elongated, rod-like shape and disclosed parallel arrays of myofibrils. These phenotypic characteristics were maintained for at least 4 weeks in primary culture. The evolution of this tissue-like organizational pattern was dependent upon specific interactions between the NHCs and the collagen-based matrix that were mediated by the cardiac alpha 1 beta 1 integrin complex. This conclusion was supported by a variety of experimental results. Altering the tertiary structure of the matrix or blocking the extracellular domains of either the cardiac alpha 1 or beta 1 integrin chain inhibited the expression of the tissue-like pattern of organization. Neither cell-to-cell contact or contractile function were necessary to induce the formation of the rod-like cell shape. However, beating activity was necessary for the assembly of a well-differentiated myofibrillar apparatus. These data suggest that the cardiac alpha 1 beta 1 integrin complex serves to detect and transduce phenotypic information stored within the tertiary structure of the surrounding matrix.
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PMID:Modulation of cardiac myocyte phenotype in vitro by the composition and orientation of the extracellular matrix. 792 12

Significant bone mass reduction occurs in stroke patients on the hemiplegic side compared with the intact side, correlating with the degree of paralysis and vitamin D deficiency. To evaluate the influence of long-standing immobilization on this osteopenia, we measured various serum markers of bone metabolism in 93 hemiplegic elderly patients with a long-standing stroke and in 37 controls. The bone mineral density (BMD) of the second metacarpal was determined bilaterally. The scoring of the stroke patients activity was based on the Barthel Index (BI). The serum ionized calcium was higher in the patients than in the controls, correlating negatively with the BI in the patients. The concentrations of parathyroid hormone (PTH), pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen and bone Gla protein were normal or low. The serum 25-hydroxyvitamin D level was low in the patients, correlating positively with the BMD on both sides. The serum 1,25-dihydroxyvitamin D (1,25-[OH]2D) level was markedly reduced in the patients. Hemiplegia from a stroke can result in immobilization hypercalcemia which inhibits PTH secretion and 1,25-[OH]2D production. Bone remodelling may have almost reached an equilibrium, resulting in a steady rate of bone loss. This and the hypovitaminosis D appear to be the dominant causes of immobilization-induced osteopenia in elderly, long-standing hemiplegic stroke patients.
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PMID:Influence of immobilization on bone mass and bone metabolism in hemiplegic elderly patients with a long-standing stroke. 1022 20

Significant reduction in bone mineral density (BMD) occurs in stroke patients on the hemiplegic and contralateral sides, correlating with the degree of paralysis and vitamin D and K deficiency due to malnutrition, and increasing the risk of hip fracture. We evaluated the efficacy of vitamin K2 (menatetrenone: menaquinone-4; MK-4) in maintaining BMD by comparing serum biochemical indices of bone metabolism between treated and untreated patients. In a random and prospective study, of 108 hemiplegic patients following stroke, 54 received 45 mg menatetrenone daily (MK-4 group, n = 54) for 12 months, and the remaining 54 (untreatment group) did not. Nine patients excluded from the study. The BMD in the second metacarpals and serum indices of bone metabolism were determined. BMD on the hemiplegic side increased by 4.3% in the MK-4 group and decreased by 4.7% in the untreated group (p < 0.0001), while BMD on the intact side decreased by 0.9% in the MK-4 group and by 2.7% in the untreated group (p < 0.0001). At baseline, patients of both groups showed vitamin D and K1 deficiencies, high serum levels of ionized calcium, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), and low levels of parathyroid hormones (PTH) and bone Gla proteins (BGP), indicating that immobilization-induced hypercalcemia inhibits renal synthesis of 1, 25-dihydroxyvitamin D (1, 25-[OH]2D) and compensatory PTH secretion. Both vitamins K1 and K2 increased by 97.6% and 666.9%, respectively, in the MK-4 group. Correspondingly, a significant increase in BGP and decreases in both ICTP and calcium were observed in the MK-4 group, in association with a simultaneous increase in both PTH and 1, 25-[OH]2D. One patient in the untreated group suffered from a hip fracture, compared with none in the MK-4 group. The treatment with MK-4 can increase the BMD of disused and vitamin D- and K-deficient hemiplegic bone by increasing the vitamin K concentration, and it also can decrease calcium levels through inhibition of bone resorption, resulting in an increase in 1, 25-[OH]2D concentration.
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PMID:Menatetrenone ameliorates osteopenia in disuse-affected limbs of vitamin D- and K-deficient stroke patients. 973 52

A 1,25-dihydroxyvitamin D [1,25-(OH)2D] deficiency and immobilization-related increased serum calcium concentration have been observed in hemiplegic stroke patients. To elucidate the influence of increased serum calcium concentration on bone metabolism, we measured serum biochemical indices and bone mineral density (BMD) in the second metacarpals of 170 elderly subjects with hemiplegic stroke and 72 age-matched healthy controls. Serum concentrations of 25-hydroxyvitamin D [25-(OH)D], 1,25-(OH)2D, ionized calcium, intact parathyroid hormone (PTH), intact bone Gla protein (BGP), and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) were measured. An increased serum calcium concentration (mean 2.543 mEq/L) was observed in this population and correlated negatively with the Barthel index (mean 66), indicating immobilization-induced bone resorption with consequent increased serum calcium. Decreased serum concentrations of 1,25-(OH)2D (mean 25.0 pg/mL) and serum 25-OHD concentration (mean 11.6 ng/mL) were noted. Serum PTH was not increased (mean 34.8 pmol/L). Serum levels of BGP were decreased significantly, whereas serum ICTP concentrations were elevated (mean 15.2 ng/mL). A strong negative correlation was seen between the serum calcium concentration and 1,25-(OH)2D (p < 0.0001). BMD of the second metacarpal in patients was decreased significantly compared with control subjects and highly correlated with 25-(OH)D and 1,25-(OH)2D concentrations. Immobilization-related increased serum calcium levels may inhibit PTH secretion, and thus 1,25-(OH)2D production. In addition, 25-(OH)D insufficiency also may contribute to decreased concentration of 1,25-(OH)2D.
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PMID:Effect of immobilization upon renal synthesis of 1,25-dihydroxyvitamin D in disabled elderly stroke patients. 1007 22

A significant reduction in bone mineral density occurs in stroke patients on the hemiplegic side, correlating with the degree of paralysis and vitamin D deficiency due to malnutrition, sunlight deprivation, and immobilization-induced hypercalcemia, and increases the risk of hip fracture. We evaluated the effect of ipriflavone and 1alpha-hydroxyvitamin D3 [1alpha(OH)D3; vitamin D3] administration on bone mineral density preservation as compared with untreated controls. In a randomized and prospective study of 103 patients with hemiplegia after stroke (the mean duration of illness was 4.8 yr), 68 (34 patients in each group) were given 600 mg ipriflavone or 1 microg vitamin D3 daily for 12 mo, whereas the remaining 35 patients received no drug. Bone mineral density on the hemiplegic side decreased by 1.4% in the ipriflavone group, 3.8% in the vitamin D3 group, and 5.4% in the control group (P < .0001, ipriflavone v vitamin D3 and control). At baseline, all three groups of patients showed a 25-hydroxyvitamin D insufficiency, increased serum ionized calcium, and low levels of 1, 25-dihydroxyvitamin D, suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of 1, 25-dihydroxyvitamin D. After treatment, the serum 1, 25-dihydroxyvitamin D level increased by 139.9% in the ipriflavone group and by 26.9% in the vitamin D3 group. Significant decreases in the serum ionized calcium and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen, and increases in parathyroid hormone and bone Gla protein were observed in the ipriflavone group, whereas no changes occurred in the other two groups. One patient in the untreated group suffered a hip fracture, compared with none in the ipriflavone and vitamin D3 groups. These results suggest that ipriflavone is more efficacious than vitamin D3 in the prevention of decreased bone mineral density in hemiplegic stroke patients because it decreases serum calcium levels through inhibition of bone resorption and cause a subsequent increase in 1, 25-dihydroxyvitamin D concentration.
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PMID:Effect of ipriflavone on bone in elderly hemiplegic stroke patients with hypovitaminosis D. 2935 Nov 3

Hip fractures on the paretic side are a serious post-stroke complication and may result from disuse hemiosteopenia, hypovitaminosis D, and an increasing risk of falls. To evaluate short-term immobilization effects, we assessed calcium metabolism in 89 patients 1 week after the hemiplegic stroke and in 36 controls. Patient activity was rated using the Barthel index (BI). Sera from stroke patients and control subjects were assayed for ionized calcium, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OHD), 1, 25-dihydroxyvitamin D (1,25-(OH)(2)D), bone Gla protein (BGP; a bone formation marker) and pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP; a bone resorption marker). Patients' serum concentrations of ionized calcium and ICTP were higher than in controls and correlated negatively with BI; their BGP concentrations were low, correlating positively with BI. Concentrations of serum 25-OHD, 1,25-(OH)(2)D, and PTH also were low; serum 25-OHD was at a deficient level (<10 ng/ml) in nine patients (10%), an insufficient level (10-20 ng/ml) in 56 (63%), and a sufficient level (>20 ng/ml) in only 24 (27%). PTH correlated negatively with calcium and 1,25-(OH)(2)D. Hypovitaminosis D is common in acute stroke patients. Immobilization from acute hemiplegia can increase bone resorption and serum calcium, and inhibit PTH secretion and 1,25-(OH)(2)D production to add to the effects of hypovitaminosis D.
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PMID:Influence of immobilization upon calcium metabolism in the week following hemiplegic stroke. 1083 74

Significant decreases in bone mineral density (BMD) occur on the hemiplegic side in chronic stroke patients, which correlate with the degree of paralysis and hypovitaminosis D. In this double-blind, randomized, and prospective study of 98 patients with hemiplegia involving both an upper and lower extremity (55 males and 53 females; mean age, 71.4 +/- 0.6 years) after an acute stroke, 49 were given etidronate for 56 weeks and 49 received a placebo. The BMD was measured by computed X-ray densitometry (CXD) of the second metacarpal bone bilaterally. Forty age-matched control subjects were followed for 56 weeks. At baseline, both groups had 25-hydroxyvitamin D [25(OH)D] insufficiency, increased serum ionized calcium and pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), and low serum concentrations of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25(OH)2D], suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of 1,25(OH)2D. The BMD on the hemiplegic side decreased by 2.3% and 4.8% in the etidronate and placebo groups, respectively (p = 0.0003). After treatment, the serum 1,25(OH)2D concentration increased by 62.2% in the etidronate group and decreased by 12.4% in the placebo group. The etidronate group had significant decreases in the serum ionized calcium and ICTP and increases in PTH and bone Gla protein (BGP), whereas the placebo group had higher serum calcium and ICTP concentrations but stable PTH. These results suggest that etidronate can prevent decreases in the BMD in hemiplegic stroke patients because it decreases the serum calcium through inhibition of bone resorption and causes a subsequent increase in the serum 1,25(OH)2D concentration.
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PMID:Beneficial effect of intermittent cyclical etidronate therapy in hemiplegic patients following an acute stroke. 2775 30

Stroke increases the risk of hip fracture on the affected side. Although bone is lost by 1 year, rapidity of onset and relationship with immobility are uncertain. Using the bone resorption marker urinary cross-linked N telopeptide of type I collagen (uNTx), we examined bone resorption in the first 4 weeks after stroke, relating uNTx with bone density and mobility in subjects over 60 years. Two separate control groups acted as comparators, healthy (HC) and institutionalized (IC) controls, the latter to control for the effects of institutionalization. uNTx, urinary calcium (both related to creatinine and log-transformed), heel bone mineral density (BMD), Tinetti scores, and Barthel scores for prestroke function were measured. Log uNTx/Cr was lower in males compared with females, but this difference was not evident in stroke or IC subjects. Log uNTx/Cr was inversely related with BMD in females from both control groups and in male stroke subjects. Tinetti scores were divided into tertiles and were lower in stroke than IC subjects (P < 0.01). Log uNTx/Cr was similar in stroke and IC subjects in the lowest Tinetti tertile. Log uNTx/Cr was higher in stroke subjects of both sexes in the lowest tertile compared with the higher two tertiles combined (P < 0.05) and higher in all tertiles compared with HC subjects (P < 0.05). Subjects with a prestroke Barthel index of < or = 17 had higher log uNTx/Cr compared with HCs. Log uCa/Cr was higher only in male stroke patients. Bone resorption in stroke starts early, and measures to reduce this are merited.
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PMID:Bone resorption in stroke and institutionalized subjects. 1914 79

Better assessment of the association between cardiovascular disease and osteoporosis in older men may help identify shared etiologies for bone and heart health in this population. We assessed the association of BMD and bone turnover markers (BTMs) with risk of cardiovascular events (myocardial infarction or stroke) in 744 men >or=50 yr of age. During the 7.5-yr prospective follow-up, 43 strokes and 40 myocardial infarctions occurred in 79 men. After adjustment for confounders (age, weight, height, smoking, education, physical activity, self-reported history of diabetes, hypertension, and prevalent ischemic heart disease), men in the lowest quartile of BMD at the spine, whole body, and forearm had a 2-fold increased risk of cardiovascular events. Men in the highest quartile of bone resorption markers (deoxypyridinoline [DPD], C-telopeptide of type I collagen) had a 2-fold increased risk of cardiovascular events (e.g., multivariable-adjusted hazard ratio [including additional adjustment for BMD] was 2.11 [95% CI: 1.26-3.56], for the highest quartile of free DPD relative to the lowest three quartiles). The results were similar for men without prevalent ischemic heart disease and for myocardial infarction and stroke analyzed separately. Our data suggest that men with low BMD or high bone resorption may be at increased risk of myocardial infarction and stroke in addition to fracture. Thus, men with osteoporosis may benefit from screening for cardiovascular disease. Further study to elucidate the biological mechanism shared by bone and vascular disease may help efforts to identify men at risk or develop treatment.
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PMID:Increased bone resorption is associated with increased risk of cardiovascular events in men: the MINOS study. 1945 64

Hypertensive patients have an increasing risk of osteoporosis. A recent case-controlled study has demonstrated that anti-hypertensive therapy reduced a risk of fracture in these patients. In this study, we investigated whether amlodipine protects against the reduction in bone density in stroke-prone spontaneously hypertensive rats (SHR-sp). Oral dosing of amlodipine (0.5 and 3.0mg/kg/day) was started when SHR-sp were 3 months old, and continued for 3 months. At the end of the experiment, bone density of femur and serum concentrations of calcium, parathyroid hormone (PTH) and C-telopeptide of type I collagen (CTx), reflecting osteoclast activity, were measured. The bone density dose-dependently increased by the treatment with amlodipine. In addition, amlodipine reduced serum concentrations of calcium, PTH and CTx. This study showed that amlodipine prevents the reduction in bone density during the repeated dosing in SHR-sp. Amlodipine might exert its effect through a direct inhibition of osteoclast function and/or suppression of PTH secretion and subsequent inhibition of osteoclast activity.
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PMID:Protective effect of amlodipine against osteoporosis in stroke-prone spontaneously hypertensive rats. 2019 79


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