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Yoshihiro Sato

Publications and source records attributed to Yoshihiro Sato.

At least 37 records · Page 2Linked to original sources

Comparative therapeutic effects of alendronate and alfacalcidol on cancellous and cortical bone mass and mechanical properties in ovariectomized osteopenic rats.

The purpose of the present study was to compare the therapeutic effects of alendronate and alfacalcidol on the cancellous and cortical bone mass and mechanical properties in ovariectomized osteopenic rats in a head-to-head fashion. Twenty-five female Sprague-Dawley rats, 7 mo of age, were randomly divided by the stratified weight method into four groups: the sham-operated control (Sham) group and three ovariectomized groups treated with vehicle, alendronate (2.5 mg/kg, p.o., daily), or alfacalcidol (0.5 microg/kg, p.o., daily). Treatment was started 6 wk after the surgery and continued for 6 wk. At the end of the experiment, urinary deoxypyridinoline (DPD) and serum osteocalcin (OC) levels were evaluated, and cancellous and cortical bone histomorphometric analyses were performed for the proximal tibial metaphysis and tibial diaphysis, respectively. Alendronate prevented the elevation of the urinary DPD level induced by ovariectomy (OVX), and markedly decreased the serum OC level to below the value observed in the Sham group, while alfacalcidol prevented the elevation of the urinary DPD and serum OC levels induced by OVX. Alendronate increased the cancellous bone volume/total tissue volume (BV/TV) relative to the values observed in the OVX-Vehicle group by preventing the increases in the eroded surface/bone surface (ES/BS), osteoclast surface (OcS)/BS, and bone formation rate (BFR)/BS induced by OVX. However, it decreased the mineral apposition rate (MAR) in the ovariectomized osteopenic rats to below the value observed in the Sham group. It also prevented the increase in the marrow area (Ma Ar) caused by OVX. Alfacalcidol increased the BV/TV relative to the values observed in the OVX-Vehicle group by decreasing the ES/BS and OcS/BS, but maintaining the BFR/BS. The effect of alfacalcidol on the BV/TV was more pronounced than that of alendronate, despite the less pronounced suppression of OcS/BS by this drug in the ovariectomized osteopenic rats. In addition, this drug increased the cortical area (Ct Ar) and prevented the increase in the Ma Ar in the ovariectomized osteopenic rats by decreasing the endocortical ES/BS, and even increasing the endocortical BFR/BS. Furthermore, it also prevented the reduction in the maximum load of the femoral distal metaphysis in the ovariectomized osteopenic rats. Thus, the present study clearly showed that alendronate and alfacalcidol had differential therapeutic effects on the cancellous and cortical bone mass and mechanical properties in ovariectomized osteopenic rats.

Alendronate↗

Comparative effects of risedronate and calcitriol on cancellous bone in rats with glucocorticoid-induced osteopenia.

OBJECTIVES: To compared the effects of risedronate (Ris) and calcitriol (Cal) on cancellous bone in rats with glucocorticoid (GC)-induced osteopenia. MATERIALS AND METHODS: Thirty female Sprague-Dawley rats, 4 mo of age, were randomly divided by the stratified weight method into three groups of 10 rats each according to the following treatment schedule: 8-wk GC administration with 4-wk vehicle (control), Ris, and Cal as therapeutic treatment initiated after 4-wk GC administration. The GC (methylprednisolone sodium succinate, 5.0 mg/kg, s.c.), Ris (10 microg/kg, s.c.), and Cal (0.1 microg/kg. p.o.) were administered 3 times a week. At the end of the 8-wk treatment period, two-dimensional (2D) bone histomorphometric analysis was performed for cancellous bone of the proximal tibial metaphysis, 3D micro-computed tomographic analysis was performed for the distal femoral metaphysis, and the mechanical strength of the distal femoral metaphysis was evaluated by a compression test. RESULTS: Ris and Cal treatment increased both 2D and 3D cancellous bone mass. However, Ris treatment exhibited more pronounced effects on 2D and 3D cancellous bone mass than Cal treatment, and the effects of both Ris and Cal treatment were greater on 3D cancellous bone mass than on 2D cancellous bone mass. The response of 2D and 3D cancellous bone mass to Ris treatment was characterized by its effect on trabecular number and thickness, which was associated with markedly suppressed bone resorption and bone formation in terms of suppressed bone turnover. On the other hand, the response of 2D cancellous bone mass to Cal treatment was attributed to the effect of Cal on 2D trabecular thickness, and the response of 3D cancellous bone mass to Cal treatment might be characterized by the effect of Cal on 3D trabecular number and thickness, with a more marked effect of trabecular thickness. These effects were primarily due to mildly suppressed bone resorption and maintained or even increased bone formation. Despite the differential effect of Ris and Cal treatment on the cancellous bone structure and bone metabolism, both treatment increased the maximum load and braking energy of the distal femoral metaphysis to a similar extent, suggesting different mechanisms for improving bone strength. CONCLUSIONS: This study showed the differential effects of Ris and Cal on cancellous bone in rats with GC-induced osteopenia.

Animals↗

Beneficial effect of pretreatment and treatment continuation with risedronate and vitamin K2 on cancellous bone loss after ovariectomy in rats: a bone histomorphometry study.

The purpose of the present study was to examine the effect of pretreatment with risedronate and/or vitamin K2 and treatment continuation with reduced dosing frequency of the drugs on the early cancellous bone loss induced by ovariectomy (OVX) in rats. Eighty female Sprague-Dawley rats, 4 mo of age, were randomized by the stratified weight method into eight groups (n= 10 in each group); rats subjected to OVX, but not sham-operated rats, were treated with vehicle, risedronate, vitamin K2 (menatetrenone), or risedronate+vitamin K2 for 4 wk before the surgery, and the treatment was either discontinued (pretreatment groups) or continued after the surgery (treatment continuation groups) for 2 wk. Sham-operated rats (controls) were treated with the vehicle throughout the experimental period. During the 4 wk prior to the surgery (pretreatment), risedronate and vitamin K2 were administered five times a week either subcutaneously at a dose of 2.5 microg/kg body weight (risedronate) or orally at the dose of 30 mg/kg body weight (vitamin K2). During the 2 wk after the surgery (treatment continuation), the dosing frequency of the drugs was reduced to twice a week. Risedronate and vitamin K2 had an anti-resorptive effect on the bone. Pretreatment with risedronate alone, but not vitamin K2 alone, prevented the loss of the cancellous bone volume/total volume (BV/TV) of the proximal tibial metaphysis after OVX. Treatment continuation with vitamin K2 alone prevented the loss of the cancellous BV/TV after OVX, while treatment continuation with risedronate alone increased the cancellous BV/TV to beyond the values in controls. Pretreatment with risedronate+vitamin K2 had a more beneficial effect in increasing the cancellous bone mass than pretreatment with risedronate alone. Treatment continuation with risedronate and/or vitamin K_ appeared to have a more beneficial effect in increasing the cancellous bone mass than the respective pretreatment. Neither the total tissue area nor the cortical area of the tibial diaphysis was affected by any treatment. The present study demonstrated that pretreatment with risedronate had a beneficial effect on the early cancellous bone loss after OVX in rats, with a more beneficial effect when combined with vitamin K2. Moreover, even though the dosing frequency of the drugs was reduced after OVX, treatment continuation appeared to be more beneficial than pretreatment for increasing the cancellous bone mass.

Absorptiometry, Photon↗

[Immobilization and hip fracture].

Hip fracture is among the most common causes of acute immobilization in elderly patients, and elderly patients with hip fracture are at high risk for a subsequent hip fracture. At baseline, both groups had high serum concentrations of ionized calcium, high urinary deoxypyridinoline (DPD) concentrations, suggesting immobilization-induced hypercalcemia. We previously showed deficiency of vitamins D and K(1) causes reduced bone mineral density (BMD) in female Alzheimer's disease (AD) patients. In a random and prospective study of AD patients, 100 patients received 45 mg menatetrenone, 1,000 IU ergocalciferol and 600 mg calcium daily for 2 years, and the remaining 100 (untreated group) did not. Treatment with MK-4 and vitamin D(2) with calcium supplements increases the BMD in elderly female patients with AD and leads to the prevention of nonvertebral fractures. The risk of hip fracture after stroke is 2 to 4 times as high as that in age-matched healthy controls. Hyperhomocysteinemia is a risk factor for both ischemic stroke and osteoporotic fractures in elderly persons. Randomized, controlled, double-blinded study of 628 consecutive elderly hemiplegic patients at least 1 year following first ischemic stroke. Patients were assigned to daily oral treatment with 5 mg of folate and 1,500 microg of mecobalamin or double placebos, and 559 completed the 2 year follow up. Plasma homocysteine levels in the decreased by 38% in the treatment group and increased by 31% in the placebo group. The number of the hip fractures per 1,000 patient-years was 10 and 43 for the treatment and placebo groups, respectively (p<0.001). In this Japanese population with a high baseline fracture risk, combined treatment with folate and vitamin B(12) is safe and effective in reducing the risk of a hip fracture in elderly stroke patients. Because of limited study power, the relative risk reduction may only be around 0.5.

Aged↗

Comparison of effect of treatment with etidronate and alendronate on lumbar bone mineral density in elderly women with osteoporosis.

The purpose of this open-labeled prospective study was to compare the treatment effects of cyclical etidronate and alendronate on the lumbar bone mineral density (BMD), bone resorption, and back pain in elderly women with osteoporosis. Fifty postmenopausal women with osteoporosis, age ranging from 55 to 86 years (mean: 70.7 years), were randomly divided into two groups with 25 patients in each group: the cyclical etidronate group (etidronate 200 mg daily for 2 weeks every 3 months) and the alendronate group (5 mg daily). The BMD of the lumbar spine (L1-L4) measured by DXA, the urinary cross-linked N-terminal telopeptides of type I collagen (NTX) level measured by the enzyme-linked immunosorbent assay, and back pain evaluated by the face scale score were assessed at baseline, 6 months, and 12 months. There were no significant differences in baseline characteristics including age, body mass index, years since menopause, lumbar BMD, urinary NTX level, and face scale score between the two treatment groups. Etidronate treatment sustained the lumbar BMD following a reduction in the urinary NTX level and improved back pain, while alendronate treatment reduced the urinary NTX level more significantly, resulting in an increase in the lumbar BMD, and similarly improved back pain. No serious adverse events were observed in either group. This study confirmed that alendronate treatment had a greater efficacy than etidronate treatment in increasing the lumbar BMD through the reduction of bone resorption in elderly women with osteoporosis.

Aged↗

Nickel-catalyzed enantioselective three-component coupling of bis-1,3-dienes, aldehydes, and dimethylzinc.

Nickel-catalyzed three-component coupling of bis-1,3-dienes, aldehyde, and dimethylzinc was investigated. In the presence of catalytic amounts of Ni(acac)2 and PPh3, bis-1,3-dienes smoothly react with an aldehyde and dimethylzinc via intramolecular cyclodimerization of bis-1,3-diene moiety. The reaction proceeds through formation of a cyclic bis-allylnickel complex, insertion of an aldehyde, and addition of dimethylzinc to the resulting oxanickellacycle intermediate. An enantioselective coupling was also achieved by the use of a chiral monodentate phosphine ligand, H-MOP.

Aldehydes↗

Cardiac involvement in malignant syndrome in Parkinson's disease.

Little is known about cardiac abnormalities in neuroleptic malignant syndrome (NMS) in Parkinson's disease (PD), although high levels of serum creatine kinase (CK) suggest the presence of cardiac involvement. We have also been aware of elevated serum myosin light chain I (MLCI) in these patients with no clear evidence of an acute coronary syndrome. To evaluate cardiac involvement in NMS in PD, we recorded the electrocardiogram (ECG) and measured serum MLCI and CK-MB levels. Plasma levels of noradrenaline and adrenaline were also determined. The patients were classified based on the in-hospital outcome into 55 survivors and 5 nonsurvivors. Age- and gender-matched PD patients without NMS served as controls (n = 51). All patients had high serum concentrations of CK-MB and MLCI. The mean values of CK, CK-MB, MLCI, adrenaline and noradrenaline were higher in both patient groups as compared to control subjects, and the values in nonsurvivors were significantly higher than those in survivors. A positive correlation was observed between serum MLCI and CK levels (p < 0.01), and between serum MLCI levels and plasma noradrenaline concentrations (p < 0.01). ECG abnormalities such as prolonged QTc interval, abnormal Q wave, ST elevation and T wave inversion were observed in all nonsurvivors and 32 (58.2%) survivors. We conclude that myocardial involvement is common in patients with NMS even when they have no symptoms suggestive of myocardial injury, and MLCI and CK-MB as well as ECG are useful indicators of mortality.

Case-Control Studies↗

Prevention and treatment of corticosteroid-induced osteoporosis.

Osteoporosis is one of the most serious complications of corticosteroid treatment. Loss of bone mineral density (BMD) and fractures occur early in the course of corticosteroid treatment, and thus early recognition of fracture risk and effective intervention based on evidence-based-medicine (EBM) are needed. A study of meta-analysis representing the highest level in a hierarchy of evidence showed that when the outcome measure of interest was limited to changes in lumbar spine BMD, bisphosphonates were the most effective of the agents studied in comparison with no therapy or treatment with calcium, and were also more efficacious than either vitamin D or calcitonin; the efficacy of bisphosphonates was enhanced when used in combination with vitamin D. Randomized controlled trials (RCTs) representing the second level in a hierarchy of evidence showed that bisphosphonates stabilized BMD not only in the lumbar spine, but also in the hip, and that parathyroid hormone (PTH) markedly increased lumbar spine BMD. According to the EBM, bisphosphonates and possibly PTH are suggested to be the most efficacious for preserving BMD. The efficacy of these agents in reducing the incidence of vertebral fractures in patients exposed to corticosteroids remains to be established in meta-analysis studies, although some RCTs have demonstrated the anti-fracture effects of etidronate, alendronate, and risedronate in the spine. Further RCTs of fracture prevention conducted on a large number of patients and their meta-analysis are needed to confirm the efficacy of bisphosphonates, PTH, or other agents in preventing vertebral and nonvertebral fractures.

Adrenal Cortex Hormones↗

Low-dose vitamin D prevents muscular atrophy and reduces falls and hip fractures in women after stroke: a randomized controlled trial.

OBJECTIVE: Vitamin D supplementation is suggested to reduce the risk of falls among ambulatory or institutionalized elderly subjects. The present study was undertaken to address the reduced risk of falls and hip fractures in patients with long-standing stroke by vitamin D supplementation. METHODS: Ninety-six elderly women with poststroke hemiplegia were followed for two years. Patients were randomly assigned to one of the two groups, and 48 patients received 1,000 IU ergocalciferol daily, and the remaining 48 received placebo. The number of falls per person and incidence of hip fractures were compared between the two groups. Strength and tissue ATPase of skeletal muscles on the nonparetic side were assessed before and after the study. RESULTS: At baseline, serum 25-hydroxyvitamin D levels were in the deficient range (<10 ng/ml) in all patients; and vitamin D treatment enhanced serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels. Vitamin D treatment accounted for a 59% reduction in falls (95% CI, 28-81%; p = 0.003). There were increases in the relative number and size of type II muscle fibers and improved muscle strength in the vitamin D-treated group. Hip fractures occurred in 4 of 48 placebo group and 0 in 48 vitamin D2 group during the 2-year study period (log-rank, p = 0.049). CONCLUSION: Vitamin D may increase muscle strength by improving atrophy of type II muscle fibers, which may lead to decreased falls and hip fractures.

Accidental Falls↗

Efficacy of oral etidronate for skeletal diseases in Japan.

Etidronate is an oral bisphosphonate compound that is known to reduce bone resorption through the inhibition of osteoclastic activity. The efficacy of etidronate for involutional (postmenopausal and senile) and glucocorticoid-induced osteoporosis, as well as that for other skeletal diseases, was reviewed in Japanese patients. Cyclical etidronate treatment (200 mg or 400mg/day for 2 weeks about every 3 months) increases the lumbar bone mineral density (BMD) in patients with involutional osteoporosis and prevents incident vertebral fractures in patients with glucocorticoid-induced osteoporosis. The losses of the lumbar BMD in patients with liver cirrhosis and the metacarpal BMD in hemiplegic patients after stroke are prevented, and the lumbar BMD is possibly increased, preventing fragile fractures in adult patients with osteogenesis imperfecta type I. Furthermore, proximal bone resorption around the femoral stem is reduced and some complications may be prevented in patients who undergo cementless total hip arthroplasty. Oral etidronate treatment may also help to transiently relieve metastatic cancer bone pain followed by a decrease in abnormally raised bone resorption in patients with painful bone metastases from primary cancer sites, such as the lung, breast and prostate. Thus, oral etidronate treatment is suggested to be efficacious for osteoporosis, as well as other skeletal diseases associated with increased bone resorption, in Japanese patients. Randomized controlled trials needed to be conducted on a large number of patients to confirm these effects.

Administration, Oral↗

Amelioration of osteoporosis and hypovitaminosis D by sunlight exposure in hospitalized, elderly women with Alzheimer's disease: a randomized controlled trial.

UNLABELLED: In a random and prospective study, Alzheimer's disease (AD) patients were assigned to regular sunlight exposure (n = 132) or sunlight deprivation (n = 132) and followed for 1 year. Serum 25-OHD level increased by 2.2-fold in the sunlight-exposed group. Eleven patients sustained fractures in the sunlight-deprived group, and three fractures occurred among the sunlight-exposed group (p = 0.0362; odds ratio = 3.7). INTRODUCTION: A high incidence of fractures, particularly of the hip, represents an important problem in patients with Alzheimer's disease (AD), who are prone to falls and have osteoporosis. We previously showed that 25-hydroxyvitamin D (25-OHD) deficiency caused by sunlight deprivation with compensatory hyperparathyroidism causes reduced BMD in elderly women with AD. This study was undertaken to address the possibility that sunlight exposure with calcium supplementation may maintain BMD and reduce the incidence of nonvertebral fractures in elderly women with AD. MATERIALS AND METHODS: In a random and prospective study, AD patients were assigned to regular sunlight exposure (n = 132) or sunlight deprivation (n = 132) and followed for 1 year. BMD of the second metacarpal bone was measured using a computed X-ray densitometer (CXD). The CXD method measures BMD and cortical thickness at the middle of the second metacarpal bone on a radiogram of the hand and an aluminum step wedge as a standard (20 steps; 1 mm/step). Incidence of nonvertebral fractures in the two patient groups during the 1-year follow-up period was assessed. RESULTS AND CONCLUSION: At baseline, average hospitalization period was 1.7 years in both groups, and activity of daily living (ADL) was decreased. Patients of both groups showed vitamin D deficiency caused by sunlight deprivation and decreased dietary intake of vitamin D with compensatory hyperparathyroidism. The exposed group patients were exposed to sunlight (3615 minutes/year). BMD increased by 2.7% in the sunlight-exposed group and decreased by 5.6% in the sunlight-deprived group (p < 0.0001). Serum 25-OHD level increased from 24.0 to 52.2 nM in the sunlight-exposed group. Eleven patients sustained fractures in the sunlight-deprived group, and three fractures occurred among the sunlight-exposed group (p = 0.0362; odds ratio = 3.7). Sunlight exposure can increase the BMD of vitamin D-deficient bone by increasing 25-OHD concentration and lead to the prevention of nonvertebral fractures.

25-Hydroxyvitamin D 2↗

Risedronate therapy for prevention of hip fracture after stroke in elderly women.

BACKGROUND: There is a high incidence of hip fractures in patients with hemiplegic stroke. Bone mineral density (BMD) is decreased in the hemiplegic side in patients after stroke, correlating with the degree of paralysis and of hypovitaminosis D. OBJECTIVE: To evaluate the efficacy of risedronate in reducing the severity of osteoporosis and in decreasing the risk of hip fractures in elderly women following an acute stroke. METHODS: This was a 12-month, randomized, double blind, placebo-controlled trial. In a prospective study of stroke patients, 187 patients received a daily dose of 2.5 mg risedronate for 12 months, and the remaining 187 received placebo. Incidence of hip fracture was compared between the two groups at the endpoint of the study. RESULTS: Seven patients sustained hip fractures on the hemiplegic side in the placebo group, and one hip fracture occurred in the risedronate group (p = 0.0360; OR = 7.0). BMD increased by 1.5% and decreased by 4.9% in the risedronate group and placebo group (p < 0.0001). Urinary deoxypyridinoline, a bone resorption marker, decreased by 53.4% in the risedronate group and increased by 35.8% in the placebo group. CONCLUSION: Treatment with risedronate increases bone mineral density in elderly women following an acute stroke and prevents hip fractures.

Accidental Falls↗

Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial.

CONTEXT: Stroke increases the risk of subsequent hip fracture by 2 to 4 times. Hyperhomocysteinemia is a risk factor for both ischemic stroke and osteoporotic fractures in elderly men and women. Treatment with folate and mecobalamin (vitamin B12) may improve hyperhomocysteinemia. OBJECTIVE: To investigate whether treatment with folate and vitamin B12 reduces the incidence of hip fractures in patients with hemiplegia following stroke. DESIGN, SETTING, AND PATIENTS: A double-blind, randomized controlled study of 628 consecutive patients aged 65 years or older with residual hemiplegia at least 1 year following first ischemic stroke, who were recruited from a single Japanese hospital from April 1, 2000, to May 31, 2001. Patients were assigned to daily oral treatment with 5 mg of folate and 1500 microg of mecobalamin, or double placebo; 559 completed the 2-year follow-up. MAIN OUTCOME MEASURE: Incidence of hip fractures in the 2 patient groups during the 2-year follow-up. RESULTS: At baseline, patients in both groups had high levels of plasma homocysteine and low levels of serum cobalamin and serum folate. After 2 years, plasma homocysteine levels decreased by 38% in the treatment group and increased by 31% in the placebo group (P<.001). The number of hip fractures per 1000 patient-years was 10 and 43 for the treatment and placebo groups, respectively (P<.001). The adjusted relative risk, absolute risk reduction, and the number needed to treat for hip fractures in the treatment vs placebo groups were 0.20 (95% confidence interval [CI], 0.08-0.50), 7.1% (95% CI, 3.6%-10.8%), and 14 (95% CI, 9-28), respectively. No significant adverse effects were reported. CONCLUSION: In this Japanese population with a high baseline fracture risk, combined treatment with folate and vitamin B12 is safe and effective in reducing the risk of a hip fracture in elderly patients following stroke.

Aged↗

Nickel-catalyzed regioselective synthesis of tetrasubstituted alkene using alkylative carboxylation of disubstituted alkyne.

[Reaction: see text] Syntheses of alpha-silyl-beta,beta'-dialkyl alpha,beta-unsaturated carboxylic acids were achieved from silylated alkyne, carbon dioxide, and a zinc reagent using a catalytic amount of nickel complex in the presence of an excess amount of DBU. The regioselectivity of the introduction of CO2 into disubstituted alkyne is dependent on the electronic property of the substituent R on the alkyne because the thermodynamic stability of oxanickelacycle IV or V should be affected by conjugation of the substituent R with the carboxyl group in IV or V.

Alkenes↗

Amelioration by mecobalamin of subclinical carpal tunnel syndrome involving unaffected limbs in stroke patients.

Our previous study showed that overuse of the nonparetic hand and wrist of the nonparetic side following stroke result in significantly more abnormal on the nonparetic side than on the hemiparetic side in terms of electrophysiologic indices of median nerve function. The purpose of this study was to evaluate the effects of the orally administered mecobalamin, an analogue of vitamin B12, for carpal tunnel syndrome (CTS) in the nonparetic side in patients following stroke. In a randomized open label and prospective study of stroke patients, 67 received of 1500 mug mecobalamin daily for 2 years, and the remaining 68 (untreated group) did not. At baseline, sensory nerve conduction velocity, motor nerve conduction velocity, sensory nerve action potentials (SNAP) at the wrist, palm-to-wrist distal sensory latency, palm-to-wrist SNAP, motor nerve conduction velocity compound motor action potentials, and distal motor latency of median nerve were significantly more abnormal on the nonparetic side than on the hemiparetic side or in controls. Before the treatment 21 patients (31%) of untreated and 20 patients (30%) of treated group met electrophysiologic criteria for CTS. Sensory impairment of the nonparetic side had lessened in the treated group. After 2 years, all electrophysiologic indices of nonparetic side were significantly improved in the treated group compared with those in the untreated group. The improvement from baseline of electrophysiologic parameters in sensory nerve in the treated group was greater than the improvement measured in motor nerve. There were no side effects. Oral mecobalamin treatment is a safe and potentially beneficial therapy for CTS in stroke patients.

Action Potentials↗

Platelet-activating factor enhances the expression of nerve growth factor in normal human astrocytes under hypoxia.

Nerve growth factor (NGF) is required for the survival of neurons. We have addressed the effect of platelet-activating factor (PAF), one of the mediators of ischemic injury of the brain, on NGF expression in astrocytes. Normal human astrocytes in culture were stimulated with PAF, and levels of NGF mRNA and protein were analyzed by reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA). PAF increased the expressions of NGF mRNA and protein in astrocytes in time- and concentration-dependent manners. After 48-h stimulation, 10 nmol/L PAF increased the levels of NGF protein in astrocyte-conditioned medium by 1.4-fold. The PAF-induced stimulation of NGF expression was further enhanced (2.1-fold of the control) in the cells under hypoxic culture condition. BN52021 (Ginkgolide B), an antagonist for PAF binding sites, suppressed the effect of PAF. We conclude that PAF enhances NGF gene expression in human astrocytes, and the PAF-induced increase in the expression of NGF under hypoxia may benefit the protection of the nervous tissue by promoting neuronal survival.

Astrocytes↗

Abnormal bone and calcium metabolism in immobilized Parkinson's disease patients.

To elucidate the influence of immobilization-induced hypercalcemia on bone metabolism in Parkinson's disease (PD), we measured serum biochemical indexes and bone mineral density (BMD) in the second metacarpals of 142 elderly PD patients and 99 age-matched healthy controls. Serum concentrations of 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25-[OH](2)D), ionized calcium, intact parathyroid hormone (PTH), and intact bone Gla protein (BGP) were measured. Urinary deoxypyridinoline (D-Pyr) was also measured. Increased serum calcium levels (mean, 1.27 mmol/L) were observed in PD patients, and the levels correlated negatively with the Unified Parkinson's Disease Rating Scale III (UPDRS III), indicating the presence of immobilization-induced bone resorption with resultant hypercalcemia. Decreased serum concentrations of 1,25-[OH](2)D (mean, 88.7 pmol/L) and 25-OHD (mean, 29.7 nmol/L) were noted. Serum PTH was decreased (mean, 25.2 ng/L). Serum BGP was decreased while urinary D-Pyr concentration elevated. A negative correlation was observed between 1,25-[OH](2)D levels and serum calcium or UPDRS III (P < 0.0001). In disabled PD patients, immobilization-induced hypercalcemia may inhibit secretion of PTH, which in turn suppresses 1,25-[OH](2)D production. 25-OHD insufficiency may also contribute to decreased 1,25-[OH](2)D. These abnormalities may be corrected by the suppression of bone resorption with bisphoshonate, and supplementations of calcium and vitamin D should be avoided in these patients.

Aged↗