Therapeutic effect of risedronate on cancellous and cortical bone in ovariectomized osteopenic rats: a comparison with the effects of alfacalcidol.

The purpose of the present study was to compare the therapeutic effects of risedronate (RIS) and alfacalcidol (ALF) on cancellous and cortical bone in ovariectomized osteopenic rats. Forty-two female Sprague-Dawley rats, 7 months of age, were randomized by the stratified weight method into six groups: the sham-operated control (Sham) group, and five ovariectomized groups: treated with vehicle, RIS (0.1, 1.0, or 2.5 mg/kg, p.o., daily), and ALF (0.5 microg/kg, p.o., daily). Treatment was started 6 weeks after surgery and continued for 6 weeks. Evaluation at 12 weeks after surgery revealed that ovariectomy (OVX) decreased the cancellous bone volume/total tissue volume (BV/TV) of the proximal tibial metaphysis as a result of an increase of the bone formation rate/bone surface (BFR/BS), BFR/BV, and eroded surface (ES/BS), while having no effect on the cortical area (Ct Ar) of the tibial diaphysis. OVX also decreased the maximum load of the femoral distal metaphysis, while having no effect on any mechanical property parameters of the femoral diaphysis. RIS (at all the doses) increased the BV/TV relative to the value in the OVX-Vehicle group, but the value was not restored to that observed in the Sham group. The effects of RIS (1.0 mg/kg and 2.5 mg/kg) were similar, and greater than those of RIS (0.1 mg/kg). ALF also increased the BV/TV relative to the OVX-Vehicle group, but the value was not restored to that observed in the Sham group, similar to the results of RIS (1.0 mg/kg and 2.5 mg/kg) treatment. The alterations of the structural parameters induced by RIS (at the doses) were attributable to suppression of the increase of ES/BS, BFR/BS, and BFR/BV. The alterations of the structural parameters induced by ALF were attributable to suppression of the increase of ES/BS and attenuation of the increase of BFR/BV, while the BFR/BS was maintained. ALF also increased the Ct Ar to beyond the value observed in the Sham group. RIS (at all the doses) had no effect on the mechanical properties of the femoral distal metaphysis, whereas ALF prevented the loss of the maximum load of the femoral distal metaphysis. Thus, the results of the present study show differential effects of RIS and ALF on cancellous and cortical bone in ovariectomized osteopenic rats.     

Preventive effects of Cassia auriculata L. flowers on brain lipid peroxidation in rats treated with streptozotocin

The effect of aqueous extract of the flowers of Cassia auriculata were examined on antioxidants and lipid peroxidation in the brain of streptozotocin diabetic rats. Significant increase in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione were observed in brain on treatment with Cassia auriculata flower extract (CFEt) and glibenclamide. Both the treated groups showed significant decrease in thiobarbituric reactive substances (TBARS) and hydroperoxide formation in brain, suggesting its role in protection against lipid peroxidation induced membrane damage. Since the study of induction of the antioxidant enzymes is considered to be a reliable marker for evaluating the antiperoxidative efficacy of medicinal plant, these findings are suggestions of possible antiperoxidative role played by Cassia auriculata flower extract.     

Incidence of symptomatic vertebral fractures in women of childbearing age newly treated with high-dose glucocorticoid

Background: The treatment and prevention of glucocorticoid (GC)-induced osteoporosis have been controversial in premenopausal women during their childbearing years.Objective: This study assessed the incidence and risk factors for symptomatic vertebral fracture in women of childbearing age newly treated with high-dose GC.Methods: An observational cohort study was conducted at the rheumatic center of Shimoshizu National Hospital in Chiba, Japan, from 1986 to 2006. The prevalence of symptomatic vertebral fractures, as determined by x-rays, was assessed in premenopausal (aged <50 years) women with collagen vascular disease newly treated with high-dose GC (≥20 mg/d prednisolone equivalent) compared with their counterparts who did not receive GC. Differences in the incidences of vertebral fractures were compared between groups by the Kaplan-Meier method and evaluated by the log-rank test. Hazard ratios (HRs) with 95% CIs were estimated using the Cox proportional hazards regression model.Results: A total of 373 women were assessed: 292 patients in the high-dose GC treatment group (mean [SD] initial age, 32.4 [8.2] years; initial dose, 43.8 [14.9] mg/d; follow-up time, 124.2 [75.4] months) and 81 patients in the non-GC control group (initial age, 39.3 [7.8] years; follow-up time, 106.5 [79.7] months). Symptomatic vertebral fractures occurred more frequently in the high-dose GC group (11.3%) than in the non-GC group (1.2%). Using the Cox model, the adjusted HR for the high-dose GC group was 13.96 (95% CI, 1.87–104.22) relative to the non-GC group. In the high-dose GC group, Kaplan-Meier analyses revealed that the incidence of fractures in women in their forties was significantly higher in comparison with those in their twenties (P < 0.001) and thirties (P < 0.05), and that the incidence of fractures in those who consumed alcohol (>80 g/wk of pure alcohol) was significantly higher than in those who did not (P < 0.05). The Cox model also revealed that the risk was independently higher with every 10-year increment of initial age (HR = 2.27; 95% CI, 1.46–3.53), with every GC dose increase (HR = 2.28; 95% CI, 1.58–3.31), and with each 1-gram decrease of cumulative GC dose (HR = 0.95; 95% CI, 0.93–0.98).Conclusions: In this study, high-dose GC use was associated with a significantly high prevalence of symptomatic vertebral fractures in premenopausal women with collagen vascular disease during their childbearing years. However, the fracture risk was relatively low in women of childbearing age, especially those in their twenties and thirties during the early years of treatment.     

Effects of combined administration of alfacalcidol and risedronate on cancellous and cortical bone mass of the tibia in glucocorticoid-treated young rats

The purpose of the present study was to examine the effects of combined administration of alfacalcidol (ALF) and risedronate (RIS) on cancellous and cortical bone mass of the tibia in glucocorticoid (GC)-treated young rats. One hundred and nine female Sprague-Dawley rats, 3 months of age, were randomly divided by the stratified weight method into eleven groups according to the following treatment schedule: baseline control, a 4-week age-matched control, and a 4-week GC administration with a 4-week concomitant administration of vehicle, ALF, RIS, or ALF+RIS, and an 8-week age-matched control and 8-week GC administration with a 4-week administration of vehicle, ALF, RIS, or ALF+RIS that was initiated after a 4-week administration of GC. The GC (methylprednisolone sodium succinate, 5.0 mg/kg) and RIS (10 microg/kg) were administered subcutaneously 3 times a week. ALF (0.08 microg/kg) was administered orally 5 times a week. At the end of the experiment, static and dynamic bone histomorphometric analyses were performed on cancellous bone of the proximal tibial metaphysis and cortical bone of the tibial diaphysis. A 4-week GC administration induced a loss of cancellous bone volume/total tissue volume (BV/TV) compared with the age-matched control as a result of decreased bone formation and increased bone erosion, while an 8-week GC administration induced both losses of cancellous BV/TV and of percent cortical area (Ct Ar) compared with the age-matched control as a result of decreased trabecular bone formation and increased trabecular and endocortical bone erosion. ALF prevented the loss of cancellous BV/TV at the 4th week by mildly suppressing bone erosion without reducing bone formation, and it restored cancellous BV/TV and increased percentage of Ct Ar at the 8th week by preventing a reduction in trabecular bone formation and mildly suppressing trabecular bone erosion and by strongly suppressing endocortical bone erosion, respectively. RIS restored only cancellous BV/TV at 8 weeks by strongly suppressing bone formation and bone erosion. Combined administration of ALF and RIS increased total tissue area of cortical bone at the 4th and 8th weeks by markedly increasing periosteal bone formation. The present study showed the efficacy of combined administration of ALF and RIS for the geometry of cortical bone in GC-treated rats.     

Evoked dopamine overflow is augmented in the striatum of calcitriol treated rats

Calcitriol, the active metabolite of vitamin D, has been shown to have significant effects on the brain. These actions include reducing the severity of some central nervous system lesions, possibly by upregulating trophic factors such as glial cell line-derived neurotrophic factor (GDNF). GDNF has substantial effects on the nigrostriatal dopamine (DA) system of young adult, aged and lesioned animals. Thus, the administration of calcitriol may lead to significant effects on nigrostriatal DA neuron functioning. The present experiments were designed to examine the ability of calcitriol to alter striatal DA release, and striatal and nigral tissue levels of DA. Male Fischer-344 rats were administered vehicle or calcitriol (0.3, 1.0, or 3.0 μg/kg, s.c.) once daily for eight consecutive days. Three weeks later in vivo microdialysis experiments were conducted to measure basal and stimulus evoked overflow of DA from the striatum. Basal levels of extracellular DA were not significantly affected by the calcitriol treatments. However, the 1.0 and 3.0 μg/kg doses of calcitriol led to increases in both potassium and amphetamine evoked overflow of striatal DA. Although post-mortem tissue levels of striatal DA were not altered by the calcitriol injections, nigral tissue levels of DA and its main metabolites were increased by both the 1.0 and 3.0 μg/kg doses of calcitriol. In a separate group of animals GDNF levels were augmented in the striatum and substantia nigra after eight consecutive daily injections of calcitriol. These results suggest that systemically administered calcitriol can upregulate dopaminergic release processes in the striatum and DA levels in the substantia nigra. Increases in the levels of endogenous GDNF following calcitriol treatment may in part be responsible for these changes. The ability of calcitriol to lead to augmented DA release in the striatum suggests that calcitriol may be beneficial in disease processes involving dopaminergic dysfunction.     

Age-related growth of the spleen in normal and glucocorticoid treated rats

1. Age-related changes in the growth, nucleic acid content and protein turnover of the spleen have been studied in normal male rats. 2. A rapid and marked atrophy of the spleen, was found 24 hr after exposure to cortisone or dexamethasone; increased rates of protein breakdown being primarily responsible. 3. Nonetheless, the total amount of protein synthesized in the spleen (measured in vivo) was significantly decreased (30-50%) 24 hr after exposure to these steroids. 4. This compared with only a 15% decrease in whole body protein synthesis, indicating a more pronounced hormonal effect on the spleen than on most other body tissues.     

Effect of pre- and post-surgery treatment with risedronate on trabecular bone loss in ovariectomized rats.

The purposes of the present study were to differentiate the effects of pre-surgery treatment with risedronate and post-surgery treatment with a reduced dosing frequency of risedronate on trabecular bone loss in ovariectomized rats and to determine whether post-surgery treatment with a reduced dosing frequency of risedronate would have a beneficial effect on trabecular bone loss after pre-surgery treatment with risedronate by means of bone histomorphometric analysis. The short-term experiment (6 weeks) was performed on fifty, 4-month-old, female Sprague-Dawley rats randomized into five groups (n=10 in each group). Forty rats were treated with vehicle or risedronate for 4 weeks before ovariectomy (OVX), and then treated with either vehicle or risedronate for 2 weeks following OVX (the Vehicle-OVX-Vehicle [OVX control], Vehicle-OVX-Risedronate [post-OVX treatment with risedronate], Risedronate-OVX-Vehicle [pre-OVX treatment with risedronate], and Risedronate-OVX-Risedronate [continuous treatment with risedronate] groups). The remaining 10 rats were treated with vehicle for 6 weeks, with a sham operation performed 4 weeks after the start of the experiment (the Vehicle-Sham-Vehicle [Sham control] group). During the 4 weeks prior to surgery, risedronate was administered five times a week subcutaneously at a dose of 2.5 mug /kg body weight, and during the 2 weeks after surgery, the dosing frequency was reduced to twice a week. The long-term experiment (10 weeks) had the same design as the short-term one, except that the post-OVX treatment was 6 weeks. In the short-term experiment, both pre- and post-OVX treatments with risedronate prevented trabecular bone loss of the proximal tibial metaphysis 2 weeks after OVX. In long-term experiment, however, pre- and post-OVX treatments with risedronate attenuated trabecular bone loss until 6 weeks after OVX, with pre-OVX treatment having a less pronounced effect than post-OVX treatment. In the short- and long-term experiments, pre-and post-OVX treatments had an additive effect on trabecular bone mass. The present study has shown the efficacy of pre-OVX treatment with risedronate or post-OVX treatment with a low dosing frequency of risedronate for preventing trabecular bone loss early after OVX. Post-OVX treatment with a low dosing frequency of risedronate was beneficial for attenuating trabecular bone loss late after OVX. Treatment with risedronate before OVX had an additive effect on trabecular bone mass with the treatment after OVX, suggesting that treatment with a low dosing frequency of risedronate might be acceptable for reducing OVX-induced trabecular bone loss after treatment with risedronate prior to OVX.     

Inhibition of lysyl oxidase and prolyl hydroxylase activity in glucocorticoid treated rats

Triamcinolone diacetate produced a dose dependent decrease in lysyl oxidase activity in the skin of new born rats when administered over a three day period. Maximum inhibition by this glucorticoid resulted in less than 10% of control lysyl oxidase activity. A similar though less dramatic effect was observed on skin prolyl hydroxylase activity. These results suggest that the antianabolic effect of glucocorticoids on collagen synthesis extend to enzymes involved in the intra- and extracellular modifications of collagen.     

Surface characteristics of thymocytes in glucocorticoid treated rats using rosette-formation technique and surface marker analysis.

Glucocorticoid (GC) treatment is known to induce destruction of cortical thymocytes and then their reconstitution. By using the rats treated with GC, we examined the relationship between rosette-formation and surface markers (CD4 and CD8) for clarifying the processes of differentiation and maturation in rat thymocytes. Thymus weight and thymocyte count began to decrease immediately after GC administration and became minimal on 5-7 days, followed gradual recovery. The percentage of rosette-forming thymocytes began to decrease immediately after GC treatment and became minimal on 5 days, followed by recovery to the normal level by the 10th to 14th day after treatment. During the analysis of the changes in the percentage of 4 subsets (CD4-8-, CD4+8+, CD4+8+, CD4-8+) of rat thymocytes after GC treatment, the percentage of CD4+8+ cells was found to change in close relation to the change in the percentage of rosette-forming lymphocytes, suggesting that rosette-forming thymocytes are CD4+8+ cells. These results suggest that the treatment induces destruction of GC-sensitive thymocytes, possibly rosette-forming cells, followed by migration of precursor T cells (CD4-8- cells) in the thymus, and that the precursors change into rosette-forming cells (CD4+8+ cells) in the thymus, followed by differentiation and maturation into non-rosette-forming cells (CD4+8- or CD4-8+ cells).     

Calcium absorption in corticoid treated subjects effects of a single oral dose of calcitriol

We compared the fractional absorption of calcium (FACa, 6 h, % TD) and the radiocalcium transit (% TD per min) in seven glucocorticoid-treated patients (10-25 mg prednisolone per day) and in seven normal subjects, in the basal state and 12 h after an oral dose of synthetic 1,25-(OH)2D (3 micrograms). In the basal state, the radiocalcium transit was significantly decreased (P less than 0.02) at 15 min in patients treated with prednisolone, but FACa at 6 h was not significantly decreased (51 +/- 5 vs. 60 +/- 5% TD). 12 h after an oral dose of 1,25-(OH)2D which resulted in supraphysiologic plasma levels, FACa increased significantly (P less than 0.02) in both groups but the peak absorption rate of Ca remained lower in the corticoid-treated patients than in controls (P less than 0.02). The results suggest that glucocorticoids decrease the 1,25-(OH)2D-dependent transport of calcium across the proximal small intestine.     

Hesperidin inhibits ovariectomized-induced osteopenia and shows differential effects on bone mass and strength in young and adult intact rats.

The main aim of this study was to investigate the bone-sparing effect of hesperidin, one of the main flavonoid present in oranges, in two age groups of ovariectomized female rats, compared with their intact controls. Young (3 mo) and adult (6 mo) female Wistar rats were sham operated (SH) or ovariectomized (OVX) and then pair-fed for 90 days a casein-based diet supplemented or not with 0.5% hesperidin (Hp; n = 10/group). In older rats, Hp intake led to a partial inhibition of OVX-induced bone loss, whereas a complete inhibition was obtained in younger animals. At both ages, while plasma osteocalcin concentrations were unchanged, urinary excretion of deoxypyridinoline was reduced by Hp intake, suggesting that Hp was able to slow down bone resorption. Unexpectedly, in intact young rats, Hp consumption resulted in a significant increase in bone mineral density (BMD). Indeed, 6-mo-old HpSH rats had a similar BMD to 9-mo-old nontreated SH adult rats, suggesting an accelerated bone mass gain in the young rats. In contrast, in intact adult rats, Hp did not further increase BMD but did improve their bone strength. The results of this study show a protective effect of Hp on bone loss in OVX rats of both ages without uterine stimulation and accompanied by a lipid-lowering effect. The unexpected and intriguing findings obtained in intact rats showing improved BMD in young rats and improved femoral load in adult rats merit further investigation. The bone and lipid benefits of hesperidin make it an attractive dietary agent for the management of the health of postmenopausal women.     

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

The purpose of the present study was to compare the effects of alendronate and alfacalcidol on cancellous and cortical bone mass and bone mechanical properties in ovariectomized rats. Twenty-six female Sprague-Dawley rats, 7 months of age, were randomized by the stratified weight method into four groups: the sham-operated control (Sham) group and the three ovariectomy (OVX) groups, namely, OVX + vehicle, OVX + alendronate (2.5 mg/kg, p.o., daily), and OVX + alfacalcidol (0.5 mug/kg, p.o., daily). At the end of the 8-week experimental period, bone histomorphometric analyses of cancellous bone at the proximal tibial metaphysis and cortical bone at the tibial diaphysis were performed, and the mechanical properties of the femoral distal metaphysis and femoral diaphysis were evaluated. OVX decreased cancellous bone volume per total tissue volume (BV/TV), and the maximum load of the femoral distal metaphysis, as a result of increases in serum osteocalcin (OC) levels, and also the number of osteoclasts (N.Oc), osteoclast surface (OcS) and bone formation rate (BFR) per bone surface (BS), and BFR/BV, without any effect on cortical area (Ct Ar), or maximum load of the femoral diaphysis. Alendronate prevented this decrease in cancellous BV/TV by suppressing increases in N.Oc/BS, OcS/BS, BFR/BS, and BFR/BV, without any apparent effect on Ct Ar, or maximum load of the femoral distal metaphysis and femoral diaphysis. On the other hand, alfacalcidol increased cancellous BV/TV, Ct Ar, and the maximum load of the femoral distal metaphysis and femoral diaphysis, by mildly decreasing trabecular BFR/BV, maintaining trabecular mineral apposition rate and osteoblast surface per BS, increasing periosteal and endocortical BFR/BS, and preventing an increase in endocortical eroded surface per BS. The present study clearly showed the differential skeletal effects of alendronate and alfacalcidol in ovariectomized rats. Alendronate prevented OVX-induced cancellous bone loss by suppressing bone turnover, while alfacalcidol improved cancellous and cortical bone mass and bone strength by suppressing bone resorption and maintaining or even increasing bone formation.     

Effects of IGF-I treatment on osteopenia in rats with advanced liver cirrhosis

IGF-I is an anabolic hormone which has been reported to increase bone formation in several conditions of undernutrition. Advanced liver cirrhosis is associated with osteopenia and also with low serum levels of IGF-I. Previous results showed that low doses of IGF-I increase osteoblastic activity and decrease bone reabsorption in early liver cirrhosis. The aim of this study was to evaluate whether IGF-I-treatment also induces beneficial effect on osteopenia associated with advanced cirrhosis. Rats with ascitic cirrhosis were divided into two groups: group CI (n=10) which received saline and group CI+IGF (n=10) which were treated with IGF-I (2 microg/100 g bw x day, sc, during 21 days). Healthy controls which received saline were studied in parallel (CO n=10). On the 22nd day, the animals were sacrificed, and bone parameters were analyzed in femur. Posterior-anterior diameter was similar in all groups. No significant differences were observed in bone content of calcium, total proteins, collagen and hydroxyapatite in cirrhotic rats as compared with controls. However, CI rats showed significant reductions in total bone density (-13.5%, p<0.001) assessed by densitometry and radiological study. In CI+IGF rat bone density (assessed by densitometry) improved significantly as compared with CI animals. In summary, osteopenia characterized by loss of bone mass and preserved bone composition was found in rats with advanced cirrhosis induced by CCl4 and phenobarbital in drinking water. This bone disorder is partially restored by treatment with low doses of IGF-I during only three weeks. Thus, IGF-I could be considered as a possible therapy for osteopenia associated with advanced liver cirrhosis.     

七味育肝颗粒对肝纤维化大鼠的防治作用

目的:探讨七味育肝颗粒对肝纤维化大鼠的防治作用及对基质金属蛋白酶-13(MMP-13)/基质金属蛋白酶抑制因子-1(TIMP-1)失衡的影响。方法:取大鼠随机分为空白对照组、模型对照组、秋水仙碱组(1.0×10-4g/kg)、七味育肝颗粒各干预组(3.7、7.4、14.8 g/kg)组(n=8),采用皮下注射四氯化碳、灌胃乙醇6周来复制肝纤维化动物模型,造模的同时给药组每天灌胃给药,观测七味育肝颗粒对大鼠肝功能、肝组织病理学及肝纤维化相关指标的影响,采用免疫组化法测定肝组织MMP-13、TIMP-1的表达水平。结果:与空白对照组比较,模型对照组大鼠血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)以及肝组织透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(C-Ⅳ)、TIMP-1显著升高,而MMP-13显著下降,缓解肝组织纤维化病理变化(P<0.01);与模型对照组比较,3.7、7.4、14.8 g/kg七味育肝颗粒能明显降低ALT、AST以及HA、PCⅢ、C-Ⅳ,缓解肝组织纤维化病理变化,改善肝功能,提高MMP-13活性而降低TIMP-1活性,缓解MMP-13/TIMP-1的失...     

Preventive effects of phenoxybenzamine on nitrous oxide-induced reproductive toxicity in Sprague-Dawley rats

In previous studies, we have shown that the reproductive toxicity of N2O in rats is prevented by the co-administration of either halothane or isoflurane, whereas treatment with folinic acid, which should reverse the effects of N2O on DNA production, does not prevent toxicity. These results cast doubt on the commonly held theory that inactivation of methionine synthase is the sole cause of N2O-induced reproductive toxicity, and suggest the need for other hypotheses. One such possibility is that N2O causes adverse reproductive toxicity secondary to its sympathomimetic effects. As a first step to test this theory, we studied the effects of phenoxybenzamine (PX), an alpha-1 adrenergic antagonist, on N2O-induced reproductive toxicity using a well-established in vivo rat model. On day 8 of gestation (plug day = day 0), 130 timed-pregnant Sprague-Dawley rats were injected s.c. with either 0.5 ml of either 0.9% saline (control and N2O alone groups) or PX (0.5, 5, or 50 micrograms/kg) in 0.9% saline, the latter the maximum tolerated PX dose. They were then exposed to either air (control) or 60% N2O for 24 hours (all other groups). On day 20 of gestation, cesarean sections were performed and the fetuses were removed and examined for either visceral of skeletal abnormalities. Compared with control, treatment with N2O alone resulted in increased incidences of fetal resorptions, major and minor visceral abnormalities, and minor skeletal abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preventive effects of dietary boysenberry anthocyanins on galactosamine-induced liver injury in rats

The preventive effects of the major boysenberry anthocyanins (BoAnt) on liver injury, were determined in rats with liver injury induced by galactosamine (GalN). Increases in plasma AST and ALT activities, which were all induced by the injection of GalN, were relieved by the ingestion of BoAnt, suggesting that BoAnt is a food component available to prevent liver injury.     

Preventive effects of early anti-CD4 or anti-CD8 treatment on Borna disease in rats.

Borna disease is a virus-induced, immunopathological encephalomyelitis in which CD4+ cells and macrophages dominate the pathological picture. However, significant numbers of CD8+ cells have been morphologically identified in perivascular infiltrates as well. To determine the contribution of different T-cell subsets to the pathogenesis of Borna disease, virus-infected rats were treated with monoclonal antibodies specific for CD4+ and CD8+ cells. Both types of monoclonal antibodies were able to significantly decrease or even prevent the local inflammatory reaction in the brain if given early during the infection. However, CD8-specific monoclonal antibodies appeared to be more effective than antibodies directed against CD4+ cells. Treatment initiated 4 days postinfection did not result in inhibition of encephalitis and disease. Virus titers in the brain of infected rats treated with T-cell-specific antibodies did not differ from titers in untreated infected control animals. The results indicate an important functional role of CD8+ cells, in addition to CD4+ cells, in the pathogenesis of Borna disease.     

The physical and mechanical effects of suspension-induced osteopenia on mouse long bones.

The present investigation addresses the extent of tail-suspension effects on the long bones of mice. The effects are explored in both sexes, in both forelimb and hindlimb bones, and in both diaphyseal and metaphyseal/epiphyseal bones. Two weeks of suspension provided unloading of the femora and tibiae and an altered loading of the humeri. Whole-bone effects included lower mass (approximately 10%) and length (approximately 4%) in the bones of suspended mice compared to controls. The geometric and material properties of the femora were considered along the entire length of the diaphysis and in the metaphysis/epiphysis portions as a unit. Geometric effects included lower cross-sectional cortical area (16%), cortical thickness (25%) and moment of inertia (21%) in the femora of suspended mice; these differences were observed in both distal and proximal portions of the femur diaphysis. The relative amount of bone comprising the middle 8 mm of the diaphysis was greater (3%) in the control mice than in the suspended mice. Significant mass differences between the group in the metaphysis/epiphysis were not observed. Material effects included lower %ash (approximately 2%) in the femora and tibiae as well as in the humeri of suspended mice compared to controls. With respect to the measured physical and material properties, suspension produced similar bone responses in male and female mice. The effects of suspension are manifested largely through geometric rather than through material changes.     

Food restriction suppresses muscle growth and augments osteopenia in ovariectomized rats.

We examined effects of 4 wk of food restriction on ovariectomy-related changes in muscle, bone, and plasma insulin-like growth factor I (IGF-I). Female Sprague-Dawley rats (7 mo old) were assigned to freely eating groups: sham-operated (Sham), ovariectomized (Ovx-AL), and estrogen (estradiol)-replaced Ovx (Ovx+E(2)). Ovx rats were also pair fed with Sham (Ovx-PF) or weight matched with Sham by food restriction (Ovx-FR). Ovx-AL and Ovx-PF rats had similar estrogen status and body weight; therefore, the groups were combined (group: Ovx). After treatment, body weight was approximately 10% greater in Ovx than in Sham rats (P < 0.05), and muscle weight-to-body weight ratios were comparable among all groups. Bone mineral contents of whole tibiae in Ovx-FR and Ovx were approximately 15% (P < 0.05) and approximately 6% lower than in Sham rats (P < 0.05), respectively. Plasma IGF-I was approximately 30% higher in Ovx than in Sham (P < 0.05) but was similar between Sham and Ovx-FR. IGF-I was highly correlated with body weight and muscle mass. Within non-estrogen-replaced Ovx rats, IGF-I explained approximately 19% of variance in bone mineral content after accounting for variance attributable to body weight. Findings suggest that estrogen acts indirectly on skeletal muscle and bone in rats through regulation of body growth by factors such as IGF-I.