Bone changes during simulated weightlessness in rats

Weightless environment due to prolonged Space mission results in decreased mineralisation of the weight bearing bones. Hind limb unweighting (HU) in rats by tail suspension was used to simulate the effect of weightlessness on tibia. Adult male albino rats were divided into two groups as (i) Control (CON, n = 12) and (ii) HU for 15 days (HU, n = 18). After 15 days of HU tibia from all the animals were removed and subsequently dried and ashed. The calcium content of these bones were then determined. HU resulted in atrophic changes in the weight bearing bone, tibia, due to the reductions of water content (-35.8%), organic matrix (-12.2%) and calcium content (-33.4%). The reduction in the dry wt of tibia (-13.5%) was due to proportionate reductions in the organic matrix and total mineral content of the bone. The reduction in the mineral content was solely due to the reduction in calcium content of the bone.     

Physiological properties of rat hind limb muscles after 15 days of simulated weightless environment

Weightlessness during space mission results in atrophic changes in those muscles which have maximum weight bearing function and consist primarily of slow twitch fibres. In the present study an animal model was designed to evaluate the effects of 15 days of hindlimb unloading (HU) in rats by tail suspension on the (i) weight of gastrocnemius (G), plantaris (P), both predominantly having fast twitch fibres and soleus (S) muscle, predominantly having fast twitch fibres and (ii) contractile properties viz peak twitch contraction (Pt) and peak tetanic contraction (Po) of GPS muscle. HU rats showed significant weight reductions of G (-17.9%), P (-13.3%) and S (-41.2%) muscles. Pt and Po were also reduced in HU group but when these were expressed per gm of GPS muscle, no significant changes in Pt and Po were observed. These findings confirm that HU in rats result in maximum atrophic change in those muscles which have predominantly slow twitch fibres and reductions in contractile properties of muscles are in proportion to reduction in muscle weight. Also, HU by tail suspension provides a good ground based model for developing the deconditioning of muscles as applicable to weightlessness of space and offers a scope for the development of various countermeasures.     

Withania somnifera improves bone calcification in calcium-deficient ovariectomized rats

Osteoporosis, characterized by reduction in bone density, is a significant source of mortality among the elderly, particularly in oestrogen-deficient women. We studied the effect of Withania somnifera (WS) root extract (ethanolic), which contains oestrogen-like withanolides for anti-osteoporotic activity. Female Sprague-Dawley rats were either sham operated (n = 12) or ovariectomized (n = 12) and treated with WS/vehicle (65 mg kg(-1)), orally for 16 weeks (n = 12). All rats were allowed free access to a calcium-deficient diet (0.04% Ca) and distilled water. At termination, urinary excretion of calcium (Ca) and phosphorus (P) and serum levels of Ca, P and alkaline phosphatase (ALP) were measured. Femur and tibia bones were processed for histological (histology), morphological (scanning electron microscopy, SEM), biomechanical strength (impact test) and mineral composition (ash) analysis. Ovariectomized (OVX) rats showed a significant increase in serum ALP levels and urinary Ca and P excretion. Histological findings revealed narrowed, and disappearance of, trabeculae with widened medullary spaces in the OVX group. Ash analysis showed a reduction in ash weight, percent ash, ash Ca, ash P and ash magnesium levels in the OVX group. Further, SEM examination revealed metaphyseal bone loss in femurs and impact test showed a reduction in biomechanical strength of tibias in OVX rats. WS treatment markedly prevented the above changes in OVX rats and thus may be a potential agent in the treatment of osteoporosis.     

Effects of enoxaparin on histomorphometric parameters of bones in rats

Enoxaparin sodium is a low-molecular-weight heparin. It is not clear whether the risk of development of osteoporosis after administration of low-molecular-weight heparins is lower than after administration of standard heparin. The aim of the present study was to investigate the effects of enoxaparin on histomorphometric parameters of bones in female Wistar rats (13-15 weeks old at the beginning of the experiment). Enoxaparin was administered at doses of 1000 anti-Xa IU/kg sc daily or 2000 anti-Xa IU/kg sc daily for 4 weeks. Bone mass, mineral and calcium content (in the tibia, femur and L-4 vertebra), length and diameter in the tibia and femur, and histomorphometric parameters of the tibia (periosteal and endosteal transverse growth, width of periosteal and endosteal osteoid, area of the transverse cross-section of the cortical bone in the diaphysis and area of the transverse cross-section of the marrow cavity) and the femur (width of epiphyseal and metaphyseal trabeculae, width of epiphyseal cartilage) were examined. Enoxaparin, administered at doses of 1000 anti-Xa IU/kg sc daily or 2000 anti-Xa IU/kg sc daily for 28 days, induced osteopenic changes in the rat skeletal system. The changes observed in bone histomorphometric parameters indicate that enoxaparin caused the inhibition of bone formation and intensification of bone resorption.     

In vivo antiosteoporotic activity of a fraction of Dioscorea spongiosa and its constituent, 22-O-methylprotodioscin

The antiosteoporotic activity of the 90 % EtOH fraction of the water extract of rhizomes of Dioscorea spongiosa and methylprotodioscin, its major constituent, were examined in the model of postmenopausal bone loss using ovariectomized (OVX) rats or mice. After 6 weeks treatment, the proximal tibia of rats or mice and the distal femora of mice were scanned by peripheral quantitative computed tomography (pQCT). Both the 90 % EtOH fraction (100 mg/kg/d) and methylprotodioscin (50 mg/kg/d) significantly inhibited bone loss in bone mineral content (BMC) and bone mineral density (BMD) in total, cancellous and cortical bones, and the decrease in bone strength indexes induced by OVX, without side effect on the uterus.     

局部根区水分胁迫下钙对冬小麦生长及养分吸收的影响--测试文章

以小偃22为材料，采用Hoagland营养液进行分根培养试验，研究了局部根区水分胁迫下，钙对冬小麦幼苗生长及养分吸收的影响。设置2个钙水平处理（正常供钙和不供钙）、3种水分处理（正常水分、局部根区水分胁迫和全部根区水分胁迫），共6个处理。结果表明：不论是否水分胁迫，缺钙处理冬小麦幼苗的株高、主根长、生物量、叶绿素相对含量（SPAD值）、相对含水量及地上部N、P、Ca含量和根系N、P、K、Ca含量均显著低于正常供钙处理(P＜0.05)。正常供钙条件下，局部根区水分胁迫使株高增加4.4%，正常水分、局部根区水分胁迫和全部根区水分胁迫的植株生物量分别为1.54、1.66 g·株^-1和0.97 g·株^-1，比缺钙处理分别高19.4%、25.8%和4.3%；全部根区水分胁迫下，冬小麦的株高及主根长均显著降低。缺钙条件下，植株对N、P、Ca等养分的吸收显著降低。正常供钙条件下，正常水分、局部根区水分胁迫和全部根区水分胁迫处理地上部全氮含量分别为36.54、36.65 g·kg^-1和32.70 g·kg^-1，比缺钙处理分别高9.5%、6.5%和6.9%；全磷含量分别为7.48、7.51 g·kg^-1和6.54 g·kg^-1，比缺钙处理分别高3.0%、13.1%和22.7%；全钙含量分别为8.35、8.37 g·kg^-1和5.53 g·kg^-1，比缺钙处理分别高26.5%、24.4%和19.7%。结果说明钙显著影响冬小麦幼苗生长发育和养分利用，钙可促进局部根区水分胁迫下冬小麦幼苗的生长及其对养分的吸收，缓解全部根区水分胁迫的抑制效应。     

Hydroxyurea-induced cell death in human T lymphoma cells as related to imbalance in DNA/protein cycle and deoxyribonucleotide pools and DNA strand breaks.

The aim of this study was to elucidate the mechanism(s) behind the cellular toxicity of therapeutic concentrations of hydroxyurea (HU). Treatment of human T lymphoma cells (CCRF-CEM) with 60-100 microM of HU for 24 h decreased the growth rate by 90% due to accumulation of cells in early S phase. It induced a marked imbalance in both the DNA/protein cycle (as measured by two-parameter flow cytometry) and the deoxyribonucleotide (dNTP) pools. HU treatment did not enhance the frequency of DNA single-strand breaks (SSBs), as measured by the alkaline unwinding technique. Cell viability was unaffected. However, removal of HU led to 10-15% cell loss during the following 12 h period in parallel with increasing SSBs, and a rapid progression of cells through S and G2 stages. The unbalanced DNA to protein content per cell and the dNTP pools were normalized 6-12 and 24 h after removal of HU, respectively. These results show that marked changes in the DNA to protein ratio and dNTP pools alone are not directly lethal, but when combined with a high replicative DNA synthesis rate, as found after removal of HU, apparently lead to elevated cell death.     

Effects of doxycycline on the development of bone damage caused by prednisolone in rats

The aim of the present study was to investigate the effects of doxycycline on the development of bone damage caused by prednisolone in rats. The experiments were carried out on male WAG rats (200-260 g), divided into 2 control and 6 experimental groups receiving prednisolone (5 mg/kg im daily) or/and doxycycline (100 mg/kg po daily) for 2 or 4 weeks. The animals were sacrificed on the 15th or 29th day of the experiment and the following characteristics were examined: mass, length, mechanical properties, mineral and calcium content in the tibia and femur, width of endosteal and periosteal osteoid, endosteal and periosteal transverse growth, transverse cross-section area of the diaphysis and of the marrow cavity in the tibia, width of epiphyseal cartilage and width of trabeculae in the femur. Prednisolone caused features of osteopenia (inhibition of bone formation and intensification of bone resorption), which were stronger after 4 weeks of the experiment. Doxycycline administered alone for 2 or 4 weeks intensified the processes of bone formation and resorption. Doxycycline to some degree attenuated the influence of prednisolone on rat bones.     

Effect of zinc-containing β-tricalcium phosphate nano particles injection on jawbone mineral density and mechanical strength of osteoporosis model rats

Zinc-containing β-tricalcium phosphate (ZnTCP) nano particles were injected into zinc-deficient rats to promote osteogenesis. Sprague-Dawley (SD) rats (4 weeks old, average weight of 70 g) were divided into four groups: Normal rats (not ovariectomized (OVX)), Control rats (OVX), and OVX rats injected with a suspension of ZnTCP nano particles or ZnSO(4). The ZnTCP contained 6.17% zinc. The suspensions (0.6 mg as a zinc volume/0.2 ml) were injected around the jaw bone once a week for 12 weeks. Local effects on the bone mineral content (BMC) of jawbone, and systemic effects on body weight, the BMC of both femurs determined by X-ray computed tomography, and bone mechanical strength (BMS) measured by the three-point bending method, were examined. The BMC of jaw bone was significantly higher in the ZnTCP-treated group than un-treated or ZnSO(4)-treated group. Body weight, the BMC of femurs, and BMS were also significantly higher in the ZnTCP treated-group. The zinc-containing β-tricalcium phosphate nano particles were effective at preventing bone loss induced by ovariectomy in rats and have potential uses for treating periodontitis.     

高山红景天细胞悬浮培养生长和产物积累动力学

目的研究高山红景天悬浮细胞生长、红景天多糖和红景天苷合成动力学特征,为培养过程的优化控制提供理论依据。方法考察1个培养周期内高山红景天细胞的鲜重、干重和红景天苷、红景天多糖的含量,绘制生长曲线、生长速率曲线和比生长速率曲线。结果高山红景天细胞悬浮培养的生长周期约为16 d,0~4 d为细胞的延滞期,4~12 d为对数期,13~15 d为稳定期,在第14天时细胞鲜、干质量达到最大,分别为266.13 g.L-1和13.41 g.L-1;红景天苷在培养的第12天达到最大,其质量分数为0.585%;第10天时红景天多糖的含量达到最大,其(质量分数为13.824%)。结论确定细胞生长和产物积累的变化规律,可以提高生产效率,为培养过程的优化控制提供理论依据。     

SD大鼠阿霉素慢性心力衰竭模型的建立与评价

目的通过尾静脉注射阿霉素建立SD大鼠慢性心力衰竭模型,并对其进行评价。方法成年♂SD大鼠随机分为两组:正常对照组(CON组,n=8)和阿霉素心力衰竭组(ADR组,n=20)。ADR组尾静脉注射阿霉素2 mg.kg-1,每周1次,计6周,累积剂量达12 mg.kg-1;CON组静脉注射等容积0.9%的氯化钠溶液,周期同前。末次注射2周后图测定心功能包括左心室舒张末内径(LVEDD)和收缩末内径(LVESD)并计算左室短轴缩短率(LVFS)及射血分数(LVEF);病理学检测包括HE及VG染色观察心肌组织形态学改变;ELISA法测定血浆BNP浓度。结果与CON组相比,ADR组大鼠LVEDD和LVESD增加,LVFS和LVEF明显下降(P<0.01);HE染色可见部分心肌纤维断裂,心肌间质炎细胞浸润;VG染色心肌间质胶原容积分数(CVF)及心肌血管周围胶原面积(PVCA)明显增加(P<0.01),心肌纤维化明显;血浆BNP水平升高(P<0.01)。结论静脉多次注射阿霉素能够导致SD大鼠心功能降低和心肌组织形态学改变,成功建立可靠的非缺血性慢性心力衰竭模型。     

Withdrawal reveals lack of effect of prolonged antihypertensive treatment on intrinsic aortic wall stiffness in senescent spontaneously hypertensive rats

1. Chronic antihypertensive treatment lowers cardiovascular morbidity and mortality. The beneficial effect on the blood vessel wall may be due to the lowering of blood pressure (BP) and, hence, wall stress (WS), or to a treatment-induced change in wall structure. 2. We have previously shown that, when evaluated at the same level of BP and WS, the stiffness of the aortic wall of old spontaneously hypertensive rats (SHR) is higher than that of young and adult SHR and that of age-matched Wistar-Kyoto (WKY) rats. In the present study, we tested the hypothesis that the intrinsic changes in wall composition and mechanics in old SHR can be modulated by long-term treatment with an angiotensin I-converting enzyme inhibitor (captopril; 40 mg/kg per day) combined with a diuretic (hydrochlorothiazide; 20 mg/kg per day) and that treatment withdrawal would reveal whether such changes are maintained when BP and WS return to pretreatment levels. 3. We evaluated aortic structure and mechanics in SHR following 1 week withdrawal of oral antihypertensive treatment from 3 to 15 months of age (n = 8). Results were compared with age-matched SHR that were maintained on treatment (n = 12) or were not treated (n = 13) and with WKY rats (no treatment n = 11; maintained n = 11; withdrawn n = 10). 4. Isobaric aortic wall stiffness was estimated from the ratio of baseline aortic pulse wave velocity (PWV) to BP and the slope relating aortic PWV to BP following sodium nitroprusside-induced hypotension. Relative wall stiffening was estimated as the ratio of elastic modulus (EM) to WS. We argued that if treatment produced a change in wall elastin or collagen content, with a subsequent decrease in isobaric wall stiffness, then this would be maintained when BP increased following withdrawal of treatment. 5. In old SHR, treatment lowered isobaric wall stiffness (baseline PWV/BP 4.6 +/- 0.3 cm/s per mmHg; slope relating PWV to BP 6.7 +/- 0.4 x 10-3 cm/s per mmHg and EM/WS 4.1 +/- 0.4 vs 6.1 +/- 0.4 cm/s per mmHg, 9.7 +/- 0.9 x 10-3 cm/s per mmHg and 8.9 +/- 1.1, respectively, without treatment; all P < 0.05). After 1 weeks treatment withdrawal, the indices (5.7 +/- 0.2 cm/s per mmHg, 9.1 +/- 0.2 x 10-3 cm/s per mmHg and 7.2 +/- 0.6) increased in parallel with the increase in WS to levels similar to those observed in untreated SHR. There were no significant differences among the WKY rat groups. 6. Treatment increased the elastin and collagen contents of the aortic wall in both SHR (196 +/- 13 and 128 +/- 5 vs 111 +/- 9 and 86 +/- 4 mg/g wet weight, respectively, in untreated; P < 0.05) and WKY rats (190 +/- 19 and 135 +/- 4 vs 115 +/- 7 and 114 +/- 5 mg/g wet weight, respectively, in untreated; P < 0.05). This increase remained following withdrawal (213 +/- 26 and 118 +/- 4 vs 161 +/- 14 and 127 +/- 4 mg/g wet weight in SHR and WKY rats, respectively). 7. In summary, 1 year of treatment with captopril plus hydrochlorothiazide increases wall elastin content and reduces WS and stiffness in old SHR. Following withdrawal, elastin content remains high, but wall stiffness parallels WS in a manner similar to that in untreated SHR.     

Modulation of ventricular fibrillation in the isolated heart: the role of slow calcium channel activity under continuous perfusion

The individual activities of sodium versus calcium channels in the initiation and maintenance of ventricular fibrillation (VF) have not been fully elucidated. Therefore we studied in isolated heart under nonischemic conditions (a) VF characteristics in untreated hearts, (b) initiation and maintenance of VF during attenuation and blockade of slow calcium channel activity by verapamil, (c) the effect of these interventions on the characteristics of the induced arrhythmia, and (d) the impact of heart weight on the observed results. Measurements were carried out in both ventricles of isolated feline hearts during ventricular pacing and 8 min of electrically induced tachyarrhythmias. Measurements during ventricular pacing included epicardial conduction time (CON), refractoriness (VRP), and all tissue resistivity (ATR; an indirect measure of changes in intercellular electrical coupling). Measurements during arrhythmia included ATR, peak frequency [PKF; a measure of the prevailing frequency based on Fast Fourier Transform (FFT) analysis], and normalized entropy (ENTROP; a measure of the degree of arrhythmia organization). Measurements during sinus rhythm and arrhythmia were repeated after blocking of calcium channel activity by verapamil at a high concentration (1.8x10(-4) M; n = 8) and at two low concentrations (1.5 and 3.0x10(-7) M; n = 8). In untreated hearts, mainly VF episodes were induced, exhibiting a low degree of organization with no significant change in this parameter throughout the arrhythmia (8 min). In the left ventricle (LV; and to a much smaller extent in the right ventricle; RV), a gradual increase in PKF was observed throughout the arrhythmia, with no significant change in ATR. Verapamil at a high concentration increased CON, but did not affect VRP. These findings were similar in both ventricles. In lower verapamil concentrations, CON was not affected, and VRP was slightly shortened. After treatment with a high verapamil concentration, VF could not be induced in small hearts but was always inducible in large hearts. Transient arrhythmia episodes appeared in 9% of untreated hearts, in 25% with "high" verapamil, and in 25-37% with "low" verapamil. With all verapamil concentrations, the induced arrhythmia was modulated from a predominantly VF to PVT or MVT type, manifested by a decrease in ENTROP. This effect was less pronounced with increasing heart weight. No significant change in PKF and in ATR was obtained with verapamil throughout the arrhythmia. It is suggested that verapamil modulation of arrhythmia organization is associated mainly with a direct blockade of calcium channel activity (perhaps by causing reduction in the safety factor for conduction), rather than with indirect modulation of electrophysiological parameters.     

Early deprivation and behavioral and physiological responses to social separation/novelty in the marmoset

Long-term effects of adverse early environment on neurobehavioral development have been reported for rodents and primates. The present study used daily early deprivation (ED), a paradigm developed for rats, for the first time in a nonhuman primate, the common marmoset, and investigated its effects on the behavioral and physiological responses to social separation/novelty (SSN) challenge tests in juveniles. On postnatal days (PNDs) 2-28, infants (n=5 twin pairs) were removed from the parents and placed alone in an isolation chamber for 30-120 min (9 h/week). Parents and control subjects (n=5 twin pairs) were briefly restrained (CON). At Weeks 18-20, behavioral responses of ED and CON juveniles to six 60-min SSN tests in an isolated cage, comprising 45 min alone and 15 min reunion with the father, were measured. Baseline and post-test urine samples were collected for measurement of cortisol. ED subjects exhibited significantly lower basal SSN urinary cortisol than CON, whilst SSN response cortisol values were similar in ED and CON. When alone, ED subjects were significantly less mobile and emitted significantly less contact calls than CON. Following reunion, ED subjects were significantly less in contact with or being carried by the father than CON and demonstrated significantly more tail piloerection. Although they require validation by additional parameters (e.g. cardiovascular), these data strongly suggest that early-life stress alters endocrine and behavioral responsiveness to psychosocial challenge in this primate and in a direction that could model important changes in disorders of human affective state.     

Effects of low, moderate and relatively high chronic exposure to cadmium on long bones susceptibility to fractures in male rats

The study investigated the risk of the femur and tibia fractures on a male rat model of low, moderate and relatively high human exposure to cadmium (1, 5 and 50mg Cd/l in drinking water for 12 months). Bone mineral density (BMD) and biomechanical properties at the proximal and distal femur, and femoral and tibial diaphysis as well as the bone content of mineral and organic components, were evaluated. The exposure to 1mg Cd/l caused only very subtle changes in biomechanical properties at the femoral neck and distal femur. In the rats treated with 5mg Cd/l, a decrease in the distal femur BMD (by 5.5%) and enhanced vulnerability to fracture at the femoral neck, distal femur, and tibia diaphysis were observed. At the highest Cd treatment, the BMD decreased (by 6.5-11%) and the biomechanical properties weakened at all regions of the femur and tibia. Moreover, a decrease in the femur and tibia content of mineral components (by 11.5% and 10%, respectively) and the tibia content of organic components (by 7%) was noted. The results seem to indicate that low chronic exposure to Cd can have no influence on the bone resistance to fracture, whereas moderate (and particularly relatively high) exposure seriously increases the risk of fracture of long bones in males. The observations, together with our findings on an analogous female rat model, provide evidence that males are less vulnerable to Cd-induced demineralization and weakening of biomechanical properties of the femur and tibia than females.     

小鼠肝硬化导致骨丢失及人参茎叶皂苷的防治作用

目的　探讨肝硬化与骨质疏松的关系并观察人参茎叶皂苷对肝硬化导致的骨丢失的防治作用。方法用CCl₄致小鼠肝纤维化,观察与肝损伤相关的各种指标及测定股骨的骨Ca²⁺量和其他矿物质含量。结果　单用CCl₄小鼠呈现典型的慢性肝损伤后肝硬化的改变,骨重量和骨钙总量明显减少,而骨铜和骨镁显著增高。而人参茎叶皂苷防治组有明显的护肝及对抗骨丢失作用。结论　人参茎叶皂苷在所用的剂量下对肝硬化及骨丢失有一定预防作用     

Effects of fenfluramine on the metabolism of calcium and phosphorus in the rat: fenfluramine effects on Ca and P metabolism.

Daily administration of 2, 5, 10, 15 and 20mg of fenfluramine/kg body weight to adult rats for four weeks resulted in dose dependent decrease in calcium and phosphorus absorption with an inverse correlation of r = -0.94 for calcium and r = -0.93 for phosphorus. Significant (P less than 0.05) increase in the total faecal lipids and moderate decline in plasma calcium levels were also observed in the rats. Adult rats made obese by dietary methods when treated with 10mg and 15 mg of fenfluramine/kg body weight/day for 10 weeks showed a significant reduction (p less than 0.001) in the intestinal absorption of both calcium and phosphorus. The reduction at 15mg/kg drug dose was 10.7 pc for calcium and 9.5 pc for phosphorus. Analyses of the long bones as well as carcasses of the obese rats showed significant decrease (p less than 0.001) in the content of these minerals. Plasma calcium and phosphorus levels were also significantly (p less than 0.001) reduced in the obese-treated rats. However, fenfluramine treatment significantly reduced the plasma calcium but not the phosphorus levels in the non-obese rats. These studies have demonstrated that chronic administration of fenfluramine (greater than or equal to 10mg/kg body weight) to rats, obese or non-obese, impairs calcium and phosphorus metabolism in the body.     

因卡膦酸二钠对W_(256)肿瘤引起的溶骨作用的影响

目的　通过一种体内模型 ,观察因卡膦酸二钠(YM175)的主要药效学。方法　试验大鼠分为 6个组 :正常、模型和阳性药 (帕屈膦酸钠 15mg·kg-1)对照以及YM1753个剂量 (0 6、1 2与 2 4mg·kg-1)组 ;除正常组以外 ,每鼠右后肢胫骨上端骨旁肌肉内注入 0 2mlW2 56瘤细胞悬液 (4×10 6个瘤细胞 )。 12h后尾静脉一次注射受试药和对照药 ,对照组iv等量的生理盐水。d13收集尿、血、骨等样品 ,检测钙等生化学指标 ,并进行患肢X光片的骨密度微机图像分析。结果　YM1753种剂量对W2 56性溶骨大鼠的血钙、2 4h尿钙排泄量和AKP活性的升高以骨密度、骨灰重量的降低均有明显的纠正作用。结论　YM175对恶性肿瘤性溶骨及其伴有的高钙血症具有良好的防治作用     

Oral administration of beta-cryptoxanthin prevents bone loss in streptozotocin-diabetic rats in vivo

The effects of beta-cryptoxanthin, a carotenoid, on bone components in the femoral-diaphyseal and -metaphyseal tissues of streptozotocin (STZ)-diabetic rats was investigated. Rats received a single subcutaneous administration of STZ (6.0 mg/100 g body weight), and then the animal were orally administered beta-cryptoxanthin (5 or 10 microg/100 g body weight) once daily for 7 or 14 d. The administration of STZ caused a significant decrease in body weight and a significant increase in serum glucose, triglyceride, and calcium levels, indicating a diabetic state. These alterations were significantly prevented by the administration of beta-cryptoxanthin (5 or 10 microg/100 g) for 14 d. The administration of beta-cryptoxanthin (5 or 10 microg/100 g) to normal rats for 14 d did not have a significant effect on body weight or on serum glucose, triglyceride, and calcium levels. Calcium content, alkaline phosphatase activity, and DNA content in the femoral-diaphyseal and -metaphyseal tissues were significantly decreased in STZ-diabetic rats. These decreases were significantly prevented by the administration of beta-cryptoxanthin (5 or 10 microg/100 g) for 14 d. The administration of beta-cryptoxanthin to normal rats for 14 d caused a significant increase in calcium content, alkaline phosphatase activity, and DNA content in the femoral-diaphyseal and -metaphyseal tissues. This study demonstrates that the intake of beta-cryptoxanthin has a preventive effect on bone loss in STZ-diabetic rats.     

Skeletal changes in multiparous mice fed a nutrient-sufficient diet containing cadmium

Female mice were given nutrient-sufficient, purified diets containing either 0.25, 5, or 50 ppm Cd. One-half of the females were bred for 6 consecutive 42-day rounds of pregnancy/lactation (PL mice); remaining females were non-pregnant controls (NP mice). PL mice and NP controls were sacrificed after 1, 2, 4, or 6 consecutive rounds of pregnancy/lactation. No consistent, cadmium-dependent decreases in body weight, femur calcium content, or calcium/dry weight (Ca/DW) ratio occurred among the NP mice during the 252 days of cadmium exposure. In contrast, significant, cadmium-dependent decreases in body weight (3-11%), femur calcium content (15-27%), and Ca/DW ratio (5-7%) occurred in the multiparous mice exposed to 50 vs 0.25 ppm Cd. In addition, among the PL mice, the effect of cadmium was dose-dependent, with femur calcium contents decreasing significantly as the cadmium exposure level increased from 0.25 to 5 then 50 ppm Cd (P less than 0.05). Results demonstrate that dietary cadmium exposure had a greater effect on the skeletons of dams exposed to cadmium during the stresses of pregnancy and lactation than in non-pregnant controls. The results provide evidence that the combination of cadmium exposure and multiparity may have played a role in the etiology of Itai-Itai disease in Japan.