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Biomedical subjects

Y F Ma

Publications and source records attributed to Y F Ma.

54 records · Page 3Linked to original sources
PubMed1995

Intermittent treatment of prostaglandin E2 with risedronate is more anabolic than prostaglandin E2 alone in the proximal tibial metaphysis of ovariectomized rats.

This study is designed to test how intermittent application of prostaglandin E2 (PGE2) and risedronate (Ris) alone or in combination acts on the cancellous bone mass in estrogen-deficient rats. Sprague-Dawley rats were ovariectomized (ovx) or sham-ovx'd at 6 months of age. PGE2 (6mg/kg/d), Ris (5 micrograms/kg/twice a week) or PGE2 plus Ris were given for 60 days to ovx rats immediately after operation and followed by 60 days without treatment. The drugs were then reapplied for another 60 days. Static histomorphometry was performed on the secondary spongiosa of proximal tibial metaphysis (PTM). Sixty days of ovx lost trabecular bone and number, Ris prevented ovx-induced bone loss. PGE2 added 48% extra cancellous bone, but the new bone was completely lost after 60 days of withdrawal. Another 60 days of PGE2 treatment only partially restored the trabecular bone, the bone mass was still -42% lower than that of sham-ovx controls. Co-treatment of PGE2 with Ris added the same amount of bone as PGE2 alone after the first 60 days treatment period, but differed from PGE2 alone in that the new bone lost less during the 60 days withdrawal period. Re-application of co-treatment for another 60 days added more extra bone. We concluded that intermittent co-treatment with anabolic and anti-resorptive agents is more effective than anabolic agent alone in long-term therapy of cancellous bone in estrogen-deficient rats.

Analysis of Variance↗
PubMed1995

Intermittent treatments of prostaglandin E2 plus risedronate and prostaglandin E2 alone are equally anabolic on tibial shaft of ovariectomized rats.

Effects of intermittent administration of prostaglandin E2 (PGE2), risedronate (Ris) and their combination on bone mass were studied on the cortical bone of tibial shafts of ovariectomized (ovx) rats. Six month old ovx rats were treated immediately after operation with subcutaneous injections of 6 mg PGE2/kg/d, 5 micrograms Ris/kg/2x/wk or their combination for 60 days each of an on/off/on cycle. PGE2 alone and in combination with Ris added the same amount of new bone in the first 60 days on period. During the 60 days off period, newly added endocortical and marrow trabecular bone disappeared in PGE2 alone treatment groups. In co-treatment group, the marrow trabeculae were only partly lost. There was no difference in total bone area between co-treatment and PGE2 alone groups after another 60 days on treatment. Our findings indicate that co-treatment was better in the maintenance of newly added endocortical and marrow trabecular bone during the off period; however, it formed less bone than PGE2 alone during the second treatment period, and ended up with the same amount of bone with both treatments.

Animals↗
PubMed1995

Maintenance therapy for added bone mass or how to keep the profit after withdrawal of therapy of osteopenia.

Since continuous therapy for osteoporosis can be expensive and may have detrimental effects, there is a need to develop a strategy to maintain bone mass after withdrawal of treatment. The bone maintained by estrogen and calcitonin therapies and exercise, but the added bone induced by anabolic agents disappears upon cessation of treatment. To avoid this pitfall, the concepts of activation, restore and maintain (ARM) or loss, restore and maintain (LRM), the on/off administration of combined anabolic agent with an antiresorptive or antiactivation agent, and cyclical treatment of the two regimes have been employed successfully in "keeping the profit" (maintaining bone) in preclinical studies. The data for the disappearance of bone upon cessation of certain osteopenic treatments, its mechanism of loss and the development of maintenance concept and subsequent preclinical studies indicate that there was no need for costly continuous therapy in the treatment strategy for osteoporosis.

Animals↗
PubMed1995

Effects of on/off anabolic hPTH and remodeling inhibitors on metaphyseal bone of immobilized rat femurs. Tomographical (pQCT) description and correlation with histomorphometric changes in tibial cancellous bone.

An anabolic effect of hPTH(1-38) (s.c. doses of 200 micrograms/kg/d during 75 days) on trabecular and cortical bone mass is tomographically described in the metaphyseal region of immobilized rat femurs using pQCT technology, in agreement with previous histomorphometrical studies of the proximal tibial metaphyses. Correlations between pQCT and histomorphometrical data showed that this effect derived from a stimulation of endosteal and trabecular bone modeling that induced a transference from trabecular to cortical bone mass. Loss of effects after withdrawal, resulting from a stimulation of bone remodeling, could be total or partially prevented by subsequent s.c. injections of risedronate (5 micrograms/kg/2/wk), 17-B-estradiol (10 micrograms/kg/d) or calcitonin (10 micrograms/kg/d) given during 60 days, in this order of effectiveness. The preventive potency was proportionally related to the reduction induced in histomorphometric indices of bone resorption.

Animals↗
PubMed1995

Risedronate plus prostaglandin E2 is superior to prostaglandin E2 alone in maintaining the added bone after withdrawal in a non-growing bone site in ovariectomized rats.

Effects of risedronate and prostaglandin E2 (PGE2) alone or in combination on the distal tibia, a non-growing bone site with closed epiphysis at 3 months of age, were studied in ovariectomized (ovx) rats. Six-month-old Sprague-Dawley female rats were either ovx or sham-ovx. Rats were treated immediately after operation either with risedronate (5 micrograms/kg/2x/wk), PGE2 (6 mg/kg/d), or risedronate+PGE2 for 60 days (on-groups) and followed by 60 days without treatment (off-groups). Trabecular area, width and numbers were determined in metaphyseal cancellous bone of the distal tibia. No significant bone loss or structural changes were observed in the distal tibial metaphysis after 120 days of ovx. Risedronate alone did not produce any effect on bone mass during the treatment and the withdrawal periods. PGE2 alone increased the trabecular bone mass associated with thickened trabeculae and increased trabecular numbers. However, some of the newly formed bone was lost at the end of 60 days withdrawal. Combination of risedronate and PGE2 treatment added the same amount of bone mass as PGE2 alone, and the added new bone was maintained during the 60 days withdrawal. These results indicate that treatment with risedronate and PGE2 can preserve the anabolic effect of PGE2 on bone mass for at least 60 days after treatment.

Analysis of Variance↗
PubMed1995

Effects of droloxifene on prevention of cancellous bone loss and bone turnover in the axial skeleton of aged, ovariectomized rats.

The purpose of this study was to determine the efficacy of droloxifene (DRO), an estrogen antagonist/agonist, in preventing ovariectomy (OVX)-induced lumbar vertebral cancellous bone loss and bone turnover in aged female rats. Fifty-three Sprague-Dawley female rats were OVX or sham-operated at 19 months of age, and divided into 6 groups: (I) sham-operated controls; (II) OVX vehicle controls; (III) OVX rats treated with E2 at 30 micrograms/kg/day; (IV)-(VI) OVX rats treated with DRO at either 2.5, 5, or 10 mg/kg p.o. daily. The treatment period was 8 weeks. Static and dynamic cancellous bone histomorphometric parameters were determined on 4 and 10 microns thick, undecalcified, double-fluorescent labeled sections of the fourth lumbar vertebral body. Changes in body weight, uterine weight, and total serum cholesterol were also determined. OVX for 8 weeks in 19-month-old female rats resulted in reduced trabecular bone volume (-18%) and trabecular width (-10%) and increased labeling perimeter (+52%), bone formation rate/bone surface referent (+60%), bone formation rate/bone volume referent (+77%), osteoclast number (+41%), and osteoclast perimeter (+41%). E2 treatment at 30 micrograms/kg/day for 8 weeks prevented OVX-induced cancellous bone loss and decreased bone resorption, bone formation, and bone turnover to the values of sham controls. DRO at 2.5-10 mg/kg/day completely prevented bone loss and bone turnover associated with estrogen deficiency. Osteoclast number and perimeter were significantly decreased in DRO-treated-OVX rats compared to both sham and OVX controls. Trabecular bone volume, trabecular width, labeling perimeter, bone formation rate/bone surface referent, and bone formation rate/bone volume referent showed no differences in DRO-treated OVX rats compared to those of E2-treated OVX rats and sham controls. These histomorphometric results indicated that DRO is an estrogen agonist on cancellous bone of lumbar vertebral bodies of aged, OVX rats. Further, E2 treatment prevented the OVX-induced increase in body weight gain and nonsignificantly reduced total serum cholesterol compared to OVX controls. Body weight gain and total serum cholesterol did not differ between OVX rats treated with E2 and sham controls. In OVX rats treated with DRO, body weight decreased significantly in a dose-response manner, and total serum cholesterol was significantly reduced by 65% to 70% compared to both sham and OVX controls. In addition, treatment with E2 increased uterine weight to the value of sham controls in OVX rats. However, DRO had no effect on uterine weight at either 2.5 or 10 mg/kg/day, while it only slightly but significantly increased uterine weight over OVX controls at 5 mg/kg/day. We conclude that DRO was efficacious in the prevention of lumbar vertebral cancellous bone loss and in the decline of total serum cholesterol but had no effect on uterine weight in the aged, OVX female rats. Our data suggest that DRO is a potentially useful agent for the prevention of vertebral bone loss leading to spinal fractures in postmenopausal women.

Administration, Oral↗
PubMed1995

Effects of prostaglandin E2 and F2 alpha on the skeleton of osteopenic ovariectomized rats.

This article contains the histomorphometric evaluation of the effects of prostaglandin F2 alpha (PGF2 alpha) on cancellous bone from the lumbar vertebra and cortical bone from the tibial shaft of ovariectomized, osteopenic rats. These effects were then compared with those of prostaglandin E2 (PGE2). Three-month-old rats were either ovariectomized (ovx) or sham-ovx. Then, either PGF2 alpha or PGE2 in doses of 1 and 3 mg/kg/day was given subcutaneously for 21 days at 150 days post ovx. Histomorphometric analysis was performed separately on both the primary and secondary spongiosae of the fourth lumbar vertebral bodies (LVB) and on tibial shafts. The ovx rats exhibited osteopenia in both primary (-23% to -37%) and secondary (-20%) spongiosae of the LVB, but not in the tibial shafts at 150 and 171 days post ovx. In the LVB, PGE2 in doses of 1 or 3 mg/kg/day for 21 days restored trabecular bone volume to the levels of sham-ovx controls in the primary spongiosa. However, in the secondary spongiosa, the treatments only thickened the trabeculae. The effects of the PGF2 alpha treatment were similar to those of the PGE2 in both the primary and the secondary spongiosae. While both PGF2 alpha and PGE2 treatments stimulated bone formation in the LVB as indicated by the increases in labeled perimeter, tissue and bone area-based bone formation rates, PGE2 is about 10 times more potent than PGF2 alpha in these effects. The PGE2 treatment also elevated activation frequency in the LVB, while the PGF2 alpha treatment did not. The treatments differed in that PGE2 at these dose levels did not alter the eroded surface in the LVB while PGF2 alpha decreased it significantly. Thus, the increase of the ratio of labeled to eroded perimeter in the LVB in PGF2 alpha-treated animals was much more than that in PGE2-treated animals. In the tibial shafts, PGE2 in doses of 1 and 3 mg/kg/day produced new marrow trabeculae in 2 of 6 and 3 of 6 of the ovx rats. However, no new trabecula was found in PGF2 alpha-treated tibial shafts. Higher doses of PGE2 also increased periosteal labeled perimeter, MAR, and BFR/BS, while PGF2 alpha did not produce any significant change in these parameters. Both PGE2 and PGF2 alpha in doses of 1 and 3 mg/kg/day increased the labeled perimeter, MAR and BFR/BS and decreased the eroded perimeter in the endocortical surface. We concluded that both PGF2 alpha and PGE2 in doses of 1 and 3 mg/kg/day for 21 days exhibited anabolic bone effects. The effects were mostly confined to an increase in trabecular volume in the primary spongiosa of the LVB and in the endocortical surface of tibial shafts. The tissue level mechanism behind this appears to be that PGE2 and PGF2 alpha can both stimulate osteoblast recruitment and activity. Overall, we found PGE2 to be more potent than PGF2 alpha at the same dose level at the endocortical surface. Furthermore, new marrow trabecular bone formed only after PGE2 treatment. PGF2 alpha differed from PGE2 by significantly reducing the trabecular eroded surface in ovx rats.

Animals↗
PubMed1994

Mechanical loading modifies ovariectomy-induced cancellous bone loss.

The object of this study was to determine the tissue level mechanism in which mechanical loading had an influence on ovariectomy-induced cancellous bone loss. Two experiments were performed: (1) 230 g female rats were divided into basal, age-related controls and right hindlimb immobilized (RHLI) group; (2) 250 g female rats were divided into basal, age-related, ovariectomized (OVX) controls and OVX combined with RHLI. The RHLI model immobilized (IM) or underloaded (UL) the right hindlimb and loaded (L) the left hindlimb compared to the right hindlimb. Both experiments lasted 60 days. Histomorphometric data was gathered from the secondary spongiosa of double fluorescent labeled proximal tibial metaphysis (PTM). The study confirmed that IM or UL induces cancellous bone loss, by decreasing bone formation, and increasing bone resorption and OVX results in cancellous bone loss, a higher bone turnover with bone resorption exceeding bone formation in the PTM. The OVX'd and immobilized (OVX + UL) PTM showed further decreased cancellous bone mass (-48%), decreased number (-43%), and decreased tissue-level bone formation rate (-54%) from that of OVX rats. However, the OVX'd and loaded (OVX + L) PTM partially prevented the OVX-induced cancellous bone loss. The cancellous bone area (+46%), number (+29%), and ratio of node to free end (+70%) were increased and percent eroded perimeter (-44%) and bone resorption rates (-30%) were decreased from OVX rats, but cancellous bone area and number were still significantly lower than those in age-related controls. We found that IM or UL accentuated cancellous bone loss in OVX rats by inhibiting bone formation and that loading partially prevented cancellous bone loss in OVX and RHLI rats by inhibiting bone resorption.

Adaptation, Physiological↗
PubMed1994

Interferon-gamma causes loss of bone volume in vivo and fails to ameliorate cyclosporin A-induced osteopenia.

Interferon-gamma (IFN gamma) in vitro inhibits both bone resorption and bone formation, resulting in a net decrease in bone turnover. In vivo administration of cyclosporin A (CsA) produces accelerated bone remodeling with resultant bone loss. The aim of this study was to investigate whether administration of IFN gamma to rats would favorably modify the high turnover osteopenia caused by CsA. Thirty-six male Sprague-Dawley rats were randomized into 4 equal groups to receive either CsA (15 mg/kg.day) or vehicle by gavage and IFN gamma (10(6) IU/kg.day) or vehicle by ip injection for 8 days. Group 1 received CsA vehicle plus IFN gamma vehicle; group 2 received CsA plus IFN gamma vehicle; group 3 received CsA vehicle plus IFN-gamma; group 4 received CsA plus IFN gamma. Blood was sampled on days 0, 4, and 8 for measurement of ionized calcium (Ca2+), PTH, 1,25-dihydroxyvitamin D, and bone gla protein. Tibiae were removed on day 8 after double tetracycline labeling for histomorphometric analysis. Ca2+ and PTH levels were similar in all groups during the study period. Rats receiving CsA (groups 2 and 4) had elevated levels of 1,25-dihydroxyvitamin D and bone gla protein, whereas rats receiving IFN gamma alone (group 3) had no change in levels of these parameters. Bone histomorphometry revealed that treatment with CsA and/or IFN gamma (groups 2-4) caused an increase in bone resorption surface and a decrease in some parameters of bone formation, resulting in a net loss of bone volume. Thus, IFN gamma failed to influence the osteopenia caused by CsA and on its own had adverse effects on bone in vivo. These results demonstrate that immune-mediating agents have opposing actions in vitro as compared to in vivo.

Animals↗
PubMed1991

Mutagenicity of Alternaria alternata and Penicillium cyclopium isolated from grains in an area of high incidence of oesophageal cancer--Linxian, China.

In order to study the relationship between daily consumption of mouldy food and the incidence of oesophageal cancer, we examined the mutagenicity of Alternaria alternata and Penicillium cyclopium, which seriously contaminate grain in Linxian county, China. We first examined extracts of cultured strains of A. alternata. In the reverse mutation test, positive results were obtained in 85% of strains; positive results were seen in 84% of 19/20 strains in the rec assay. Eight of ten strains induced sister chromatid exchange, and two of eight strains induced chromatid breaks. Six of seven strains induced unscheduled DNA synthesis and DNA synthesis inhibition. One extract induced a higher frequency of sister chromatid exchange in lymphocytes from normal persons than in those from patients with oesophageal cancer, and the spontaneous break-points in patients were related to fragile sites and neoplasia-associated break-points. The toxins alternariol and its monomethyl ether, produced by A. alternata, were examined in the reverse mutation assay and for unscheduled DNA synthesis. The results were similar to those obtained with extracts of the different strains. Alternariol had a four to eight times greater effect than its monomethyl ether. Of 24 strains of P. cyclopium isolated from cereals in Linxian, four were cultured with rice and 19 in Raulin-Thom medium. Cultures in Raulin-Thorn medium, solution and hyphae were then extracted. The strains cultured with rice induced sister chromatid exchange, unscheduled DNA synthesis and DNA synthesis inhibition. The solution extracts of 14 strains were positive in the rec assay, and five strains were positive in the reverse mutation test.(ABSTRACT TRUNCATED AT 250 WORDS)

Alternaria↗
PubMed1989

[Study of the efficiency and stability of harringtonine encapsulation in whole phospholipid vesicle from human erythrocyte membrane].

The whole phospholipid of human erythrocyte membrane was used to prepare small unilamellar vesicles (SUV) of harringtonine by reversed phase evaporation combined with sonication scattering method. The percentage of harringtonine encapsulation and its stability were also studied. The results showed that the concentration of phospholipid and its degree of oxidation were the main influencing factors. The percentage of harringtonine encapsulation under our experimental conditions reached 21.5%. Stability test showed that the rate of leakage of harringtonine from liposome was 7.3% when stored at 4 degrees C for two months.

Alkaloids↗
PubMedDate not supplied

Prostaglandin E2 restores cancellous bone to immobilized limb and adds bone to overloaded limb in right hindlimb immobilization rats.

The purpose of this study was to determine whether prostaglandin E2 (PGE2) can restore cancellous bone mass and architecture to osteopenic, continuously immobilized (IM), proximal tibial metaphysis (PTM) in female rats. The right hindlimb of three and one-half-month-old Sprague-Dawley female rats were immobilized by right hindlimb immobilization (RHLI) in which the right hindlimb was underloaded and the contralateral left limb was overloaded during ambulation. After 4 or 12 weeks of RHLI, the rats were treated with 3 or 6 mg PGE2/kg/day and RHLI for 8 or 16 weeks. Bone histomorphometry was performed on microradiographs of PTM. Immobilization (IM) induced a transient cancellous bone loss and decreased trabecular thickness, number and node density, and increased free end density that established a new steady state after 4 weeks of IM. Three or 6 mg PGE2/kg/d for 8 weeks beginning at 4 or 12 weeks of IM completely restored cancellous bone mass (+127% to +188%) and structure to the age-related control levels in spite of continuous IM. Another 8 weeks of treatment maintained bone mass and architecture at these levels. No differences in cancellous bone mass and architecture were found between the overloaded PTM or RHLI rats and the age-related controls. However, 3 and 6 mg/kg/d of PGE2 treatment started at 4 or 12 weeks for 8 weeks significantly increased cancellous bone mass in the overloaded PTM (+45 to +74% of untreated controls), and another 8 weeks of treatment maintained bone mass at these levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMedDate not supplied

Greater bone formation induction occurred in aged than young cancellous bone sites.

We have determined the differences in the effects of continual prostaglandin E2 (PGE2) treatment in aged (non-growing) and young (growing) cancellous bone sites in 7-month-old Sprague-Dawley rats. The sites involved are the aged distal tibial metaphysis (DTM) with a closed epiphysis and the young proximal tibial metaphysis (PTM) with a slow growing, open epiphysis. The study involved rats treated with 0, 1, 3 or 6 mg PGE2/kg/d for 60, 120 and 180 days. Static and dynamic histomorphometry of percent trabecular area, and tissue-referent bone formation rate (BFR/TV) were determined in both DTM and PTM. In pretreatment controls, the secondary spongiosa of the two metaphyses contain the same amount of cancellous bone (11% in DTM vs. 13% in PTM), but markedly less bone formation in DTM (0.6%/y in DTM vs. 41.5%/y in PTM). After 60 days of 6 mg PGE2/kg/d treatment, %Tb.Ar was increased 607% in DTM and 199% in PTM, BFR/TV was increased to nearly 14 fold in DTM and only 5 fold in PTM. These results indicated the aged metaphysis of the DTM was much more responsive to PGE2 treatment than young, growing metaphysis of the PTM. The results of 120 and 180 days treatment did not significantly differ from 60 days treatment in both sites, indicating that the effect of continuous daily PGE2 treatment were in equilibrium after 60 days. We concluded that aged metaphysis was much more responsive to PGE2 treatment than young growing metaphysis.

Aging↗
PubMedDate not supplied

Effects of prostaglandin E2 and risedronate administration on cancellous bone in older female rats.

The effects of Prostaglandin E2 (PGE2) and Risedronate (Ris) both separately and in combination (PGE2 + Ris) were studied on the intact aged female rat skeleton to determine whether the combination of PGE2 with an antiresorptive agent is more effective anabolically than PGE2 alone. Nine-month-old Sprague-Dawley rats were injected subcutaneously either with vehicle, 6 mg PGE2/kg per day, 1 or 5 micrograms Ris/kg twice a week, or 6 mg PGE2/kg per day plus 1 or 5 micrograms Ris/kg twice a week (PGE2 + 1 Ris or PGE2 + 5 Ris) for 60 days. After the treatment, we determined the longitudinal bone growth rate, the qualitative appearance of the primary spongiosa (PS), and the static and dynamic bone histomorphometry of the secondary spongiosa (SS) of the proximal tibial metaphysis (PTM) by examining undecalcified longitudinal sections after double-fluorescent labeling. The relative effects of these treatments on longitudinal bone growth were ranked as follows: PGE2 + 5 Ris > PGE2 + 1 Ris = basal > PGE2 > 1 microgram Ris = 5 micrograms Ris = aging. The density of the PS was ranked as follows: PGE2 + 5 Ris > PGE2 + 1 Ris = PGE2 = 5 micrograms Ris = 1 microgram Ris > basal = aging. The increase in density of the PS was the result of stimulated longitudinal growth and the action of bisphosphonate. Bone mass in the SS was ranked as follows: PGE2 + 5 Ris = PGE2 + 1 Ris = PGE2 > 5 micrograms Ris = 1 microgram Ris = aging = basal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Prostaglandin E2 adds bone to a cancellous bone site with a closed growth plate and low bone turnover in ovariectomized rats.

The objects of this study were to determine the responses of a cancellous bone site with a closed growth plate (the distal tibial metaphysis, DTM) to ovariectomy (OVX) and OVX plus a prostaglandin E2 (PGE2) treatment, and compare the site's response to previous findings reported for another site (the proximal tibial metaphysis, PTM). Thirty-five 3-month-old female Sprague-Dawley rats were divided into five groups: basal, sham-OVX, and OVX + 0, +1, or +6 mg PGE2/kg/d injected subcutaneously for 3 months and given double fluorescent labels before sacrifice. Cancellous bone histomorphometric analyses were performed on 20-microns-thick undecalcified DTM sections. Similar to the PTM, the DTM showed age-related decreases in bone formation and increases in bone resorption, but it differed in that at 3 months post-OVX, there was neither bone loss nor changes in formation endpoints. Giving 1 mg PGE2/kg/d to OVX rats prevented most age-related changes and maintained the bone formation histomorphometry near basal levels. Treating OVX rats with 6 mg PGE2/kg/d prevented age-related bone changes, added extra bone, and improved microanatomical structure by stimulating bone formation without altering bone resorption. Furthermore, after PGE2 administration, the DTM, a cancellous bone site with a closed growth plate, increased bone formation more than did the cancellous bone in the PTM.

Analysis of Variance↗