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1.
Objectives:This study was undertaken to elucidate the adverse effect of lead on female reproductive system following in vivo exposure in rats.Results:Marked and a significant decrease in per cent body weight gain was observed in rats of Group IV and III, respectively, compared to that in the control group. Relative uterine weights were found to decrease by 27% in Group III and IV compared to control and low dose lead treated (30 ppm) rats. Lead levels were found to increase in a linear manner in blood along with a marked increase in bone levels in 100 ppm exposure group while there was a decrease in both the blood and bones levels at 300 ppm exposure. Compared to plasma progesterone levels in rats of the control group, a nonsignificant (12.46–21.13%) reduction in plasma progesterone were observed in different lead-treated groups. No apparent gross pathological lesions were observed in any of the vital organs, including uterus. However, histopathological examination of uteri of different groups revealed lead-induced dose-dependent inflammatory changes, which were characterized by thickening of the endometrium, narrowing of uterine lumen, damage to endometrial glands and vacuolar degeneration in endometrial epithelial cells.Conclusion:Findings of this study suggest lead-induced pathophysiological alterations in myometrium, which in turn may affect the reproductive efficiency of animals.KEY WORDS: Blood, bones, histopathology, inflammation, lead, uterus  相似文献   

2.
Current treatments for osteoporosis and other bone degenerative diseases predominately rely on preventing further bone erosion rather than restoring bone mass, as the latter treatments can unintentionally trigger cancer development by undiscriminatingly promoting cell proliferation. One approach to circumvent this problem is through the development of novel chemical carriers to deliver drug agents specifically to bones. We have recently shown that carbon nanodots (C-dots) synthesized from carbon nanopowder can bind with high affinity and specificity to developing bones in the larval zebrafish. Larval bones, however, are physiologically different from adult bones in their growth, repair, and regeneration properties. Here we report that C-dots can bind to adult zebrafish bones and that this binding is highly specific to areas of appositional growth. C-dots deposition occurred within 30 minutes after delivery and was highly selective, with bones undergoing regeneration and repair showing higher levels of C-dots deposition than bones undergoing normal homeostatic turnover. Importantly, C-dots deposition did not interfere with bone regeneration or the animal’s health. Together, our results establish C-dots as a potential novel vehicle for the targeted delivery of drugs to treat adult bone disease.  相似文献   

3.
Calcium ion is an essential structural component of the skeleton. There is growing evidence for the importance of nutrition in the maintenance of bones and joints health. Nutritional imbalance combined with endocrine abnormalities may be involved in osteoporosis. For example, essential fatty acids and their metabolites were reported to have beneficial action in osteoporosis. The mechanism by which fatty acids prevent osteoporosis may involve inhibition of pro-inflammatory cytokines, which are known to have a major role in osteoporosis through induction of oxidative stress which had adverse effects on the skeleton. Other risk factors for osteoporosis, such as smoking, hypertension and diabetes mellitus are also associated with increased oxidative stress and free radicals levels. When bone fracture occurs, a remarkable yield of free radicals is generated by the damaged tissues. However, controlled production of free radicals by normally functioning osteoclasts could accelerate destruction of calcified tissues and assist bone remodeling. Enhanced osteoclastic activity observed in bone disorders may have been responsible for increased production of reactive oxygen species [ROS] in the form of superoxide, which is evident by increased levels of serum malondialdehyde [MDA] levels. One of the most damaging effects of ROS is lipid peroxidation, the end product of which is MDA which also served as a measure of osteoclastic activity. Inhibition of the antioxidant enzymes activities, such as superoxide dismutase and glutathione peroxidase, was found to increase superoxide production by the osteoclasts which represented by increased levels of MDA. Therefore, oxidative stress is an important mediator of bone loss since deficiency of antioxidant vitamins has been found to be more common in the elderly osteoporotic patients. It is concluded from this review that increased free radical production overwhelms the natural antioxidants defense mechanisms, subjecting individuals to hyperoxidant stress and thus leading to osteoporosis. In addition, administration of antioxidants might protect bones from osteoporosis and also might help in the acceleration of healing of fractured bones.  相似文献   

4.
We studied the differences in pharmacokinetics and pharmacodynamics of the same dose of alendronate administered subcutaneously as intermittent bolus injection or continuous infusion in rats. Two rat models of bone disease were applied. Bone cancer was produced by intratibial inoculation of Walker carcinosarcoma cells, and a model of augmented bone resorption was produced by vitamin D(3) treatment of rats that had undergone thyroidparathyroidectomy. Higher amounts of alendronate were found in bones and in internal organs after bolus drug administration as compared with continuous infusion. Drug effects on plasma calcium levels and on urine calcium excretion were similar in both modes of alendronate administration. Results of the study indicate that the pharmacokinetics (disposition) of alendronate is administration-dependent. The total amount found in bone does not directly represent the amount of alendronate that is pharmacologically active at the site of action in the bone and that affects bone remodeling. The findings suggest that there is no pharmacodynamic advantage for continuous infusion of alendronate. It is concluded that the preferred mode of administration should be selected according to secondary clinical criteria (like incidence of adverse effects and convenience of administration).  相似文献   

5.
Heavy metal tungsten alloys have replaced lead and depleted uranium in many munitions applications, due to public perception of these elements as environmentally unsafe. Tungsten materials left in the environment may become bioaccessible as tungstate, which might lead to population exposure through water and soil contamination. Although tungsten had been considered a relatively inert and toxicologically safe material, recent research findings have raised concerns about possible deleterious health effects after acute and chronic exposure to this metal. This investigation describes tissue distribution of tungsten in mice following oral exposure to sodium tungstate. Twenty-four 6-9 weeks-old C57BL/6 laboratory mice were exposed to different oral doses of sodium tungstate (0, 62.5, 125, and 200 mg/kg/d) for 28 days, and after one day, six organs were harvested for trace element analysis with inductively coupled plasma mass spectrometry (ICP-MS). Kidney, liver, colon, bone, brain, and spleen were analyzed by sector-field high-resolution ICP-MS. The results showed increasing tungsten levels in all organs with increased dose of exposure, with the highest concentration found in the bones and the lowest concentration found in brain tissue. Gender differences were noticed only in the spleen (higher concentration of tungsten in female animals), and increasing tungsten levels in this organ were correlated with increased iron levels, something that was not observed for any other organ or either of the two other metals analyzed (nickel and cobalt). These findings confirmed most of what has been published on tungsten tissue distribution; they also showed that the brain is relatively protected from oral exposure. Further studies are necessary to clarify the findings in splenic tissue, focusing on possible immunological effects of tungsten exposure.  相似文献   

6.
Liao Y  Yu F  Jin Y  Lu C  Li G  Zhi X  An L  Yang J 《Archives of toxicology》2008,82(1):37-43
The objective of this study was to explore the optimum combination of micronutrients used with 2,3-dimercaptosuccinic acid (DMSA) in the treatment of moderately lead-intoxicated mice. Experiment was carried out based on the orthogonal design L8(27) setting six factors with two different levels of each, and eight groups of mice were needed. Mice were exposed to lead by drinking water contaminated with 0.1% lead acetate for four consecutive weeks, and then supplemented by gavage with different combinations of micronutrients with and without DMSA as designed in the orthogonal table. Lead levels in blood, liver, kidney, brain and bone and activities of blood δ-aminolevulinic acid dehydratase (ALAD) were analyzed after cessation of supplementation. The results suggested that DMSA was the only factor which could decrease significantly lead levels in blood, liver, kidney and bone; calcium and ascorbic acid were the notable factors decreasing lead levels in blood, liver, kidney, bone and brain; zinc and calcium were the notable factors reversing the lead-inhibited activities of blood ALAD; taurine was the notable factor decreasing lead levels in kidney and brain; and thiamine was the notable factor decreasing lead levels in brain. The lowest lead level in blood, liver, kidney and bone was shown in the mice supplemented with combination of calcium and ascorbic acid along with DMSA. In conclusion, the optimum combination of micronutrients used with DMSA suggested in present study was calcium and ascorbic acid, which seemed to potentiate the chelating efficacy of DMSA in the treatment of moderately lead intoxicated mice.  相似文献   

7.
目的通过影像学观察不同神经束植入组织工程骨后对成骨活动的影响,探讨组织工程骨神经化构建的方法。方法将新西兰大白兔的骨髓基质干细胞(Bone marrow stromal cells,BMSCs)进行诱导分化为成骨细胞,与β-磷酸三钙(β-tricalcium phosphate,β-TCP)复合制作组织工程骨,分别将不同类型神经束植入组织工程骨,进行以下分组:A组,组织工程骨组;B组,感觉神经束植入组;C组,运动神经束植入组;D组,血管束(含有自主神经)植入组;E组,感觉、运动神经束联合植入组。分别用于修复兔股骨1.5cm骨缺损;各组分别在术后4、8、12周进行放射学检查,并在12周进行大体标本、骨密度检测用以比较骨缺损修复情况。结果在观察期内,有感觉神经植入的组别和血管束植入的组别具有明显的促组织工程骨骨化作用,而运动神经束植入却没有明显的促进作用。结论感觉神经束和血管束具有明显的促组织工程骨成骨作用,可以作为组织工程骨神经化构建的一种方法。  相似文献   

8.
In recent years, the use of skeletal tissue as an alternative matrix in forensic toxicology has received new interest. In cases where extreme decomposition has taken place, analysis of skeletal tissue is often the only option left. In this article, a fully validated method is presented and the distribution of clomipramine, citalopram, midazolam, and metabolites after chronically administration is examined within skeletal tissue. Rats were chronically dosed with respectively clomipramine, citalopram, or midazolam. Extracts were quantitatively analyzed using liquid chromatography?electrospray ionization?tandem mass spectrometry (LC?ESI?MS/MS). Clomipramine, citalopram, and metabolites, respectively desmethylclomipramine and desmethylcitalopram are shown to be detectable in all bone types sampled. Midazolam and its metabolite α‐OH‐midazolam could not be detected. The absence of midazolam in extracts gives an indication that drugs with pKa values under physiological pH are badly or not incorporated in bone tissue. Bone and post‐mortem blood concentrations were compared. A range of different bone types was compared and showed that the concentration is strongly dependent on the bone type. In concordance with previous publications, the humerus shows the highest drug levels. Skeletal tissue concentrations found ranged from 1.1 to 587.8 ng/g. Comparison of the same bone type between the different rats showed high variances. However, the drugs?metabolite ratio proved to have lower variances (<20%). Moreover, the drugs?metabolite ratio in the sampled bones is in close concordance to the ratios seen in blood within a rat. From this, we can assume that the drugs?metabolite ratio in skeletal tissue may prove to be more useful than absolute found concentration.  相似文献   

9.
Background: Lead exposure shares many risk factors with delinquent behavior, and bone lead levels are related to self-reports of delinquent acts. No data exist as to whether lead exposure is higher in arrested delinquents. The goal of this study is to evaluate the association between lead exposure, as reflected in bone lead levels, and adjudicated delinquency. Methods: This is a case-control study of 194 youths aged 12–18, arrested and adjudicated as delinquent by the Juvenile Court of Allegheny County, PA and 146 nondelinquent controls from high schools in the city of Pittsburgh. Bone lead was measured by K-line X-ray fluorescence (XRF) spectroscopy of tibia. Logistic regression was used to model the association between delinquent status and bone lead concentration. Covariates entered into the model were race, parent education and occupation, presence of two parental figures in the home, number of children in the home and neighborhood crime rate. Separate regression analyses were also conducted after stratification on race. Results: Cases had significantly higher mean concentrations of lead in their bones than controls (11.0±32.7 vs. 1.5±32.1 ppm). This was true for both Whites and African Americans. The unadjusted odds ratio for a lead level ≥25 vs. <25 ppm was 1.9 (95% CL: 1.1–3.2). After adjustment for covariates and interactions and removal of noninfluential covariates, adjudicated delinquents were four times more likely to have bone lead concentrations >25 ppm than controls (OR=4.0, 95% CL: 1.4–11.1). Conclusion: Elevated body lead burdens, measured by bone lead concentrations, are associated with elevated risk for adjudicated delinquency.  相似文献   

10.
Exposure to lead prenatally and early in life affects physiological, behavioral, and intellectual development in humans and other animals. The movement and storage of lead within tissues and organs and its elimination from the body influence the amounts reaching sensitive target organs such as the developing brain. In this study, young herring gulls, Larus argentatus, were used to examine the effect of mild exercise on the deposition of lead in bone, to clarify possible differences between free-ranging birds in nature and confined birds in the laboratory. Forty 2-day-old chicks were randomly assigned to one of four groups: lead treatment with and without exercise, and controls with and without exercise. Chicks in the lead treatment group received a single intraperitoneal injection of lead acetate solution (100 mg/kg); weight-matched control chicks were injected with an equal volume of isotonic saline at the same age. Chicks in the exercise groups were taken outside and encouraged to move about for 2.5 h/d; others were confined in standard cages. Chicks were sacrificed at 45 d of age and lead was analyzed by graphite furnace atomic absorption. The interaction of exercise and lead dose significantly influenced the amount of lead in the three bones examined (rib, humerus, tibiotarsus), but not in the other tissues. For the lead-treated birds, mean bone lead levels were lower in the exercised versus nonexercised birds, while the reverse was true for control chicks. The data suggest that lead storage can be partly ameliorated by exercise, that young chicks would be the most affected by lead, and that older chicks that move and have larger territories in which to move may suffer lesser effects than those in dense territories.  相似文献   

11.
In the present study, an attempt has been made to analyze the changes in the biochemical and mineral contents of lead‐intoxicated bones of Catla catla at subchronic (15.5 ppm) exposure, and also to determine whether the effects of Pb intoxication can be reversed with the chelating agent meso 2, 3‐dimercaptosuccinic acid (DMSA) on the bones of freshwater fingerlings Catla catla by using Fourier transform infrared (FT‐IR) spectroscopy, X‐ray diffraction (XRD), and atomic absorption spectrophotometer techniques. The FT‐IR spectra of the lead‐exposed bones show significant alteration in the biochemical constituents. The XRD analysis showed a decrease in crystallinity due to lead exposure. Further, the Ca, Mg, and P contents of the lead‐exposed bones were less than those of the control group, and there was an increase in the mineral contents of the bones after DMSA treatment. In conclusion, the present study suggests that the subchronic lead exposure results in severe loss of bone minerals. The overall decrease in the FT‐IR band intensity of Pb‐exposed bones relative to the control indicates a decrease in the biochemical constituents like proteins and lipids. The increase in the band intensity after treatment with chelating agent DMSA indicates increased biochemical constituents, showing that the subchronic effects of lead can be reversed by DMSA. The amide I bands observed at 1654 cm?1 in the present study suggest that the protein is dominated by α‐helical structure. © 2009 Wiley Periodicals, Inc. Environ Toxicol, 2010.  相似文献   

12.
Radiochemical and autoradiographic methods were used for 210Pb determination after Na2CaEDTA administration to rabbits. 210Pb was determined in soft tissues, compact and trabecular bones and growing microareas on the endosteum of the long bone. After Na2CaEDTA injection lead was depleted from 'new' deposits mainly on the growing surface of both trabecular and compact bones.  相似文献   

13.
Effects of cadmium on bone resorption were investigated using neonatal mouse parietal bone culture system. Cadmium at 0.5 microM and above stimulated hydroxyproline release as well as 45Ca release. As cadmium-stimulated bone resorption was inhibited by calcitonin, bone resorption induced by cadmium is osteoclast-mediated bone resorption. CI-1, collagenase inhibitor, depressed cadmium-stimulated bone resorption in a dose-dependent manner. Osteoblasts are also involved in cadmium-induced bone resorption. Indomethacin-inhibited cadmium-stimulated bone resorption and cadmium-treated bones released prostaglandin E2 to a greater extent than untreated bones. Cadmium-stimulated bone resorption was shown to be dependent on the production of prostaglandin E2. 3-Isobutyl-1-methylxanthine potentiated cadmium-stimulated bone resorption and verapamil depressed it. It is possible that an increase in levels of cAMP and calcium ion in bone cells is involved in cadmium-induced bone resorption. From these results, cadmium was found to stimulate osteoclast-mediated bone resorption which is dependent on prostaglandin E2. Second messengers in cadmium-induced bone resorption may be cAMP and calcium ion.  相似文献   

14.

Aim:

Depression is a risk factor for impaired bone mass and micro-architecture, but several antidepressants were found to increase the incidence of osteoporotic fractures. In the present study we used ovariectomized (OVX) rats as a model of osteoporosis to investigate the effects of the antidepressant bupropion on the femoral bones.

Methods:

OVX animals were treated with bupropion (30, 60 mg·kg−1·d−1) for six weeks. Bone turnover biomarkers (urinary DPD/Cr ratio, serum BALP, OC, TRAcP 5b, CTX and sRANKL levels) and inflammatory cytokines (TNF-α, IL-1β and IL-6) were determined using ELISA. Inductively coupled plasma mass spectroscopy (ICP-MS) was used to determine the femoral bone mineral concentrations. The cortical and trabecular morphometric parameters of femoral bones were determined using micro-CT scan and histopathology.

Results:

In OVX rats, the levels of bone turnover biomarkers and inflammatory cytokines were significantly elevated and femoral bone Ca2+ and PO43− concentrations were significantly reduced. Moreover, cortical and trabecular morphometric parameters and histopathology of femoral bones were severely altered by ovariectomy. Bupropion dose-dependently inhibited the increases in bone turnover biomarkers and inflammatory cytokines. OVX rats treated with the high dose of bupropion showed normal mineral concentrations in femoral bones. The altered morphometric parameters and histopathology of femoral bones were markedly attenuated by the treatment.

Conclusion:

Bupropion exerts osteo-protective action in OVX rats through suppressing osteoclastogenesis-inducing factors and inflammation, which stabilize the osteoclasts and decrease bone matrix degradation or resorption.  相似文献   

15.
The Spanish imperial eagle (Aquila adalberti) is found only in the Iberian Peninsula and is considered one of the most threatened birds of prey in Europe. Here we analyze lead concentrations in bones (n = 84), livers (n = 15), primary feathers (n = 69), secondary feathers (n = 71) and blood feathers (n = 14) of 85 individuals collected between 1997 and 2008 in central Spain. Three birds (3.6%) had bone lead concentration > 20 μg/g and all livers were within background lead concentration. Bone lead concentrations increased with the age of the birds and were correlated with lead concentration in rachis of secondary feathers. Spatial aggregation of elevated bone lead concentration was found in some areas of Montes de Toledo. Lead concentrations in feathers were positively associated with the density of large game animals in the area where birds were found dead or injured. Discontinuous lead exposure in eagles was evidenced by differences in lead concentration in longitudinal portions of the rachis of feathers.  相似文献   

16.
Reconstruction or filling of bone defects, especially in the maxillofacial region, often requires use of biomaterials. An implant should fasten healing of the bone gap or it should replace autogenic bone grafts. The combination of bone morphogenetic proteins with suitable carrier may fulfill these requirements. Proteins causing differentiation of mesenchymal cells in chondroblasts and osteoblasts were called Bone Morphogenetic Proteins--BMPs. The authors extracted BMP from bovine bones and placed it into collagen carrier formed from generally accessible hemostatic sponge--Spongostan. The implants were grafted into rat femoral muscle pouches in order to trace the tissue response. Pathologic examinations were performed 3, 6 and 8 weeks after implantation. On the basis on macroscopic and microscopic examinations it was stated that collagen sponge speckled with BMP caused minimal tissue response and evolved characteristic thin connective tissue capsule formation around the implant. The connective tissue penetrated spongious structure of the implant, filling the spaces, which became growing due to sponge resorption. Characteristic hyalinization and sparse chondroblasts were visible 8 weeks after implantation.  相似文献   

17.
Osteoporosis affects a large number of people in industrialised countries. It has clinical and public-health impacts, most importantly due to subsequent fractures. Osteoporotic fractures are one of the most common causes of disability and are associated with enormous healthcare expenditure. The majority of existing treatment options for osteoporosis only inhibit bone resorption and prevent excessive bone loss but are not capable of stimulating bone formation. However, several recent in vitro and in vivo studies in animals demonstrated that HMG-CoA reductase inhibitors stimulate the production of bone morphogenetic protein (BMP-2), which is a potent regulating protein in osteoblast differentiation and activity. This suggests that HMG-CoA reductase inhibitors may have an anabolic effect on bones, making them a potentially interesting treatment option for osteoporosis. Additionally, several studies in humans showed that some HMG-CoA reductase inhibitors may have a beneficial effect on bone turnover and may lead to an increase in bone mineral density. Consequently, several observational studies tried to evaluate whether use of HMG-CoA reductase inhibitors is associated with a decreased risk of fractures. Even though not all results of these epidemiological studies, using different designs in different study populations, were entirely consistent, they provided substantial evidence that HMG-CoA reductase inhibitor use may decrease the bone fracture risk by approximately 50%. On the other hand, reanalysis of two randomised controlled trials of HMG-CoA reductase inhibitor therapy, designed to assess cardiovascular outcomes, could not show that patients treated with HMG-CoA reductase inhibitors had a lower fracture risk in comparison with placebo-treated patients. Therefore, to conclusively assess the potential of HMG-CoA reductase inhibitors in the prevention and treatment of osteoporosis, randomised controlled trials need to be performed to address this conflicting issue. Until the results of such trials are available, practitioners should prescribe the drugs that have been proven to reduce the risk of osteoporotic fractures.  相似文献   

18.
Adult female Sprague-Dawley rats were exposed to various concentrations of lead acetate for different lengths of time. Six weeks exposure to lead acetate at concentrations of 0, 0.125, 0.25, 0.5, 1, and 2% in the drinking water, gave rise to brain and blood lead levels that were highly correlated with the lead concentration in the drinking water. When animals were exposed to 1% lead acetate for different lengths of time, an apparent delay in the rate of lead transport into the brain was seen during the first day. However, if animals were exposed for longer time periods, brain lead levels increased faster than did the blood levels. Pieces of fetal cortex cerebri were grafted to the anterior eye chamber of host animals exposed to either 1% lead acetate or to sodium acetate. Six weeks after grafting, the lead concentration in the lead-exposed grafts were 31.6 mg/kg dry wt, as compared to 6.4 mg/kg dry wt in sodium acetate control grafts. However, grafts from both groups had lead levels that were approximately five times higher than in cerebral cortex “punches” from corresponding areas of the host brains. Furthermore, zinc and copper levels were also higher in the grafts as compared to punches of in situ cortex. Taken together with previous reports on animal and human lead exposure, these data indicate that oral lead intake in adult rats bearing intraocular brain grafts yields blood and brain levels which are physiologically relevant to problems of clinical lead toxicity.  相似文献   

19.
Abstract: The effects of dichloromethylene bisphosphonate (clodronate) on the composition of bone mineral, morphology and histology of a long bone with an artificial femoral fracture were studied in a 22 week experiment. Two hundred twenty-four female rats were allocated to dose groups of 0, 3, 10, and 30 mg/kg clodronate daily subcutaneously. Bone calcium, phosphorus and magnesium concentrations remained stable and fluoride concentration rose with time. There were no statistical differences between different groups. Clodronate did not alter the histology of the callus nor delayed the healing of the fracture. It caused mild to moderate prominence of the metaphyseal area in the fractured bone in a dose- and time-dependent manner. Serum osteocalcin levels were lowered in the treated animals dose-dependently. Other serological as well as haematological values were within normal range. Clodronate seems in this experimental arrangement to be a safe agent to administer in different pathological conditions of bone even when they are complicated by fractures of long bones.  相似文献   

20.
This study presents concentration levels of trace metals and pollutants (zinc, manganese, copper, lead, and cadmium) in tissues (livers, kidneys, muscles, and bones) of shorebirds from Yeongjong Island, Korea, in the East Asian–Australian migration flyways. Essential trace elements, zinc concentrations in kidneys, and copper concentrations in muscles significantly differed among shorebirds, but manganese concentrations did not differ in each tissue. We suggest that essential elements are within normal range and are maintained there by normal homeostatic mechanism. Lead concentrations in livers, kidneys, muscles, and bones were significantly different among shorebird species. Lead concentrations in livers of Kentish Plovers, Mongolian Plovers, Dunlins, and Great Knots were less than the toxic level, and lead concentrations in livers of Terek Sandpipers were at the background level. Cadmium concentrations in livers, kidneys, muscles, and bones did not vary among shorebirds, and concentrations of cadmium in livers and kidneys were at background level in all shorebirds. In livers of Dunlins from Yeongjong Island, lead and cadmium concentrations were higher than other locations previously reported.  相似文献   

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