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Sample records for adversely affect bone

  1. Dietary restriction does not adversely affect bone geometry and mechanics in rapidly growing male wistar rats.

    PubMed

    Lambert, Jennifer; Lamothe, Jeremy M; Zernicke, Ronald F; Auer, Roland N; Reimer, Raylene A

    2005-02-01

    The present study assessed the effects of dietary restriction on tibial and vertebral mechanical and geometrical properties in 2-mo-old male Wistar rats. Two-month-old male Wistar rats were randomized to the ad libitum (n=8) or the 35% diet-restricted (DR) feeding group (n=9) for 5 mo. Tibiae and L6 vertebrae were dissected out for microcomputed tomography (microCT) scanning and subsequently fractured in biomechanical testing to determine geometrical and mechanical properties. The DR group had significantly lower mean tibial length, mass, area, and cross-sectional moment of inertia, as well as vertebral energy to maximal load. After adjustment for body mass, however, DR tibial mean maximal load and stiffness, and DR vertebral area, height, volume, and maximal load were significantly greater, relative to ad libitum means. No significant differences were found between the DR and ad libitum mineral ash fractions. Because the material properties of the tibiae between the two groups were not significantly different, presumably the material integrity of the bones was not adversely affected as a consequence of DR. The similar material characteristics were consistent with mineral ash fractions that were not different between the two groups. Vertebral maximal load and stiffness were not significant between the DR and ad libitum animals. Importantly, we show that a level of dietary restriction (35%) that is less severe than many studies (40%), and without micronutrient compensation does not adversely affect tibial and vertebral mechanical properties in young growing male rats when normalized for body mass. PMID:15585686

  2. Hyperinsulinemia adversely affects lung structure and function.

    PubMed

    Singh, Suchita; Bodas, Manish; Bhatraju, Naveen K; Pattnaik, Bijay; Gheware, Atish; Parameswaran, Praveen Kolumam; Thompson, Michael; Freeman, Michelle; Mabalirajan, Ulaganathan; Gosens, Reinoud; Ghosh, Balaram; Pabelick, Christina; Linneberg, Allan; Prakash, Y S; Agrawal, Anurag

    2016-05-01

    There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly (P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of β-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of β-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype. PMID:26919895

  3. Adverse Effects of Hyperlipidemia on Bone Regeneration and Strength

    PubMed Central

    Pirih, F; Lu, J; Ye, F; Bezouglaia, O; Atti, E; Ascenzi, MG; Tetradis, S; Demer, LL; Aghaloo, T; Tintut, Y

    2011-01-01

    Hyperlipidemia increases the risk for generation of lipid oxidation products, which accumulate in the subendothelial spaces of vasculature and bone. Atherogenic high-fat diets increase serum levels of oxidized lipids, which are known to attenuate osteogenesis in culture and to promote bone loss in mice. In this study, we investigated whether oxidized lipids affect bone regeneration and mechanical strength. Wild type and hyperlipidemic (Ldlr−/−) mice were placed on a high-fat (HF) diet for 13 weeks. Bilateral cranial defects were introduced on each side of the sagittal suture, and 5 weeks post-surgery on the respective diets, the repair/regeneration of cranial bones and mechanical properties of femoral bones were assessed. MicroCT and histological analyses demonstrated that bone regeneration was significantly impaired by the HF diet in WT and Ldlr−/− mice. In femoral bone, cortical bone volume fraction (BV/TV) was significantly reduced while cortical porosity was increased by the HF diet in Ldlr−/− but not in WT mice. Femoral bone strength and stiffness, measured by three-point bending analysis, were significantly reduced by the HF diet in Ldlr−/−, but not in WT mice. Serum analysis showed that the HF diet significantly increased levels of parathyroid hormone, TNF-alpha, calcium and phosphorus, whereas it reduced procollagen type I N-terminal propeptide, a serum marker of bone formation, in Ldlr−/−, but not in WT mice. The serum level of carboxyl-terminal collagen crosslinks, a marker for bone resorption, was also 1.7-fold greater in Ldlr−/− mice. These findings suggest that hyperlipidemia induces secondary hyperparathyroidism and impairs bone regeneration and mechanical strength. PMID:21987408

  4. FACTORS ADVERSELY AFFECTING AMPHIBIAN POPULATIONS IN THE US

    EPA Science Inventory

    Factors known or suspected to be adversely affecting native amphibian populations in the US were identified using information from species accounts written in a standardized format by multiple authors in a forthcoming book. Specific adverse factors were identified for 53 (58%) of...

  5. Excessive Growth Hormone Expression in Male GH Transgenic Mice Adversely Alters Bone Architecture and Mechanical Strength

    PubMed Central

    Lim, S. V.; Marenzana, M.; Hopkinson, M.; List, E. O.; Kopchick, J. J.; Pereira, M.; Javaheri, B.; Roux, J. P.; Chavassieux, P.; Korbonits, M.

    2015-01-01

    Patients with acromegaly have a higher prevalence of vertebral fractures despite normal bone mineral density (BMD), suggesting that GH overexpression has adverse effects on skeletal architecture and strength. We used giant bovine GH (bGH) transgenic mice to analyze the effects of high serum GH levels on BMD, architecture, and mechanical strength. Five-month-old hemizygous male bGH mice were compared with age- and sex-matched nontransgenic littermates controls (NT; n=16/group). Bone architecture and BMD were analyzed in tibia and lumbar vertebrae using microcomputed tomography. Femora were tested to failure using three-point bending and bone cellular activity determined by bone histomorphometry. bGH transgenic mice displayed significant increases in body weight and bone lengths. bGH tibia showed decreases in trabecular bone volume fraction, thickness, and number compared with NT ones, whereas trabecular pattern factor and structure model index were significantly increased, indicating deterioration in bone structure. Although cortical tissue perimeter was increased in transgenic mice, cortical thickness was reduced. bGH mice showed similar trabecular BMD but reduced trabecular thickness in lumbar vertebra relative to controls. Cortical BMD and thickness were significantly reduced in bGH lumbar vertebra. Mechanical testing of femora confirmed that bGH femora have decreased intrinsic mechanical properties compared with NT ones. Bone turnover is increased in favor of bone resorption in bGH tibia and vertebra compared with controls, and serum PTH levels is also enhanced in bGH mice. These data collectively suggest that high serum GH levels negatively affect bone architecture and quality at multiple skeletal sites. PMID:25646711

  6. Adversity before Conception Will Affect Adult Progeny in Rats

    ERIC Educational Resources Information Center

    Shachar-Dadon, Alice; Schulkin, Jay; Leshem, Micah

    2009-01-01

    The authors investigated whether adversity in a female, before she conceives, will influence the affective and social behavior of her progeny. Virgin female rats were either undisturbed (controls) or exposed to varied, unpredictable, stressors for 7 days (preconceptual stress [PCS]) and then either mated immediately after the end of the stress…

  7. Affective Disorders, Bone Metabolism, and Osteoporosis

    PubMed Central

    2013-01-01

    The nature of the relationship between affective disorders, bone mineral density (BMD), and bone metabolism is unresolved, although there is growing evidence that many medications used to treat affective disorders are associated with low BMD or alterations in neuroendocrine systems that influence bone turnover. The objective of this review is to describe the current evidence regarding the association of unipolar and bipolar depression with BMD and indicators of bone metabolism, and to explore potential mediating and confounding influences of those relationships. The majority of studies of unipolar depression and BMD indicate that depressive symptoms are associated with low BMD. In contrast, evidence regarding the relationship between bipolar depression and BMD is inconsistent. There is limited but suggestive evidence to support an association between affective disorders and some markers of bone turnover. Many medications used to treat affective disorders have effects on physiologic systems that influence bone metabolism, and these conditions are also associated with a range of health behaviors that can influence osteoporosis risk. Future research should focus on disentangling the pathways linking psychotropic medications and their clinical indications with BMD and fracture risk. PMID:23874147

  8. NSAIDs can have adverse effects on bone healing.

    PubMed

    van Esch, Robert W; Kool, Maurice M; van As, Saskia

    2013-08-01

    The science of osteoimmunology, a relatively new field of research, reveals the important interactions between the immune system and skeletal system. Interactions occur between prostaglandin metabolism, inflammatory proteins and bone metabolism. Systemic as well as local sources of inflammation appear to be actively involved in both bone formation and resorption. Non Steroidal Anti-Inflammatory Drugs (NSAIDs) can play a detrimental role in bone fractures, opposing the aim of the intervention, and can have such a negative impact on the synthesis of prostaglandins that they could even promote bone resorption. When used for a prolonged time, NSAIDs can also cause the development of an inflammatory cascade starting from the gastro-intestinal system, possibly resulting in bone resorption. Several studies show that the use of either selective or non-selective NSAIDs are intimately related to disturbances in immunological allostasis, bone metabolism and the inhibition or impediment of bone healing. PMID:23680000

  9. Adversity before conception will affect adult progeny in rats.

    PubMed

    Shachar-Dadon, Alice; Schulkin, Jay; Leshem, Micah

    2009-01-01

    The authors investigated whether adversity in a female, before she conceives, will influence the affective and social behavior of her progeny. Virgin female rats were either undisturbed (controls) or exposed to varied, unpredictable, stressors for 7 days (preconceptual stress [PCS]) and then either mated immediately after the end of the stress (PCS0) or 2 weeks after the stress ended (PCS2). Their offspring were raised undisturbed until tested in adulthood. PCS offspring showed reduced social interaction; in the acoustic startle test, PCS males were less fearful, whereas PCS females were more fearful; in the shuttle task, PCS0 males avoided shock better; and in the elevated maze, PCS0 females were more active and anxious. The 2-week interval between stress and mating assuaged the effects on offspring activity and shock avoidance but not the changes in social behavior and fear in male and female offspring. Hence, PCS to the dam, even well before pregnancy, influences affective and social behavior in her adult offspring, depending on how long before conception it occurred, the behavior tested, and sex. (PsycINFO Database Record (c) 2009 APA, all rights reserved). PMID:19209986

  10. The synthetic progestin megestrol acetate adversely affects zebrafish reproduction.

    PubMed

    Han, Jian; Wang, Qiangwei; Wang, Xianfeng; Li, Yonggang; Wen, Sheng; Liu, Shan; Ying, Guangguo; Guo, Yongyong; Zhou, Bingsheng

    2014-05-01

    Synthetic progestins contaminate the aquatic ecosystem, and may cause adverse health effects on aquatic organisms. Megestrol acetate (MTA) is present in the aquatic environment, but its possible effects on fish reproduction are unknown. In the present study, we investigated the endocrine disruption and impact of MTA on fish reproduction. After a pre-exposure period of 14 days, reproductively mature zebrafish (Danio rerio) (F0) were exposed to MTA at environmental concentrations (33, 100, 333, and 666 ng/L) for 21 days. Egg production was decreased in F0 fish exposed to MTA, with a significant decrease at 666 ng/L. The exposure significantly decreased the circulating concentrations of estradiol (E2) and testosterone (T) in female fish or 11-keto testosterone (11-KT) in male fish. MTA exposure significantly downregulated the transcription of certain genes along the hypothalamic-pituitary-gonadal (HPG) axis. MTA did not affect early embryonic development or hatching success in the F1 generation. The present study showed that MTA is a potent endocrine disruptor in fish, and short-term exposure to MTA could significantly affect reproduction in fish and negatively impact the fish population. PMID:24647012

  11. Factors affecting the development of adverse drug reactions (Review article)

    PubMed Central

    Alomar, Muaed Jamal

    2013-01-01

    Objectives To discuss the effect of certain factors on the occurrence of Adverse Drug Reactions (ADRs). Data Sources A systematic review of the literature in the period between 1991 and 2012 was made based on PubMed, the Cochrane database of systematic reviews, EMBASE and IDIS. Key words used were: medication error, adverse drug reaction, iatrogenic disease factors, ambulatory care, primary health care, side effects and treatment hazards. Summary Many factors play a crucial role in the occurrence of ADRs, some of these are patient related, drug related or socially related factors. Age for instance has a very critical impact on the occurrence of ADRs, both very young and very old patients are more vulnerable to these reactions than other age groups. Alcohol intake also has a crucial impact on ADRs. Other factors are gender, race, pregnancy, breast feeding, kidney problems, liver function, drug dose and frequency and many other factors. The effect of these factors on ADRs is well documented in the medical literature. Taking these factors into consideration during medical evaluation enables medical practitioners to choose the best drug regimen. Conclusion Many factors affect the occurrence of ADRs. Some of these factors can be changed like smoking or alcohol intake others cannot be changed like age, presence of other diseases or genetic factors. Understanding the different effects of these factors on ADRs enables healthcare professionals to choose the most appropriate medication for that particular patient. It also helps the healthcare professionals to give the best advice to patients. Pharmacogenomics is the most recent science which emphasizes the genetic predisposition of ADRs. This innovative science provides a new perspective in dealing with the decision making process of drug selection. PMID:24648818

  12. Does Ramadan Fasting Adversely Affect Cognitive Function in Young Females?

    PubMed Central

    Ghayour Najafabadi, Mahboubeh; Rahbar Nikoukar, Laya; Memari, Amir; Ekhtiari, Hamed; Beygi, Sara

    2015-01-01

    We examined the effects of Ramadan fasting on cognitive function in 17 female athletes. Data were obtained from participants of two fasting (n = 9) and nonfasting (n = 8) groups at three periods of the study (before Ramadan, at the third week in Ramadan, and after Ramadan). Digit span test (DST) and Stroop color test were employed to assess short-term memory and inhibition/cognitive flexibility at each time point. There were no significant changes for DST and Stroop task 1 in both groups, whereas Stroop task 2 and task 3 showed significant improvements in Ramadan condition (p < 0.05). Interference indices did not change significantly across the study except in post-Ramadan period of fasting group (p < 0.05). Group × week interaction was significant only for error numbers (p < 0.05). Athletes in nonfasting showed a significant decrease in number of errors in Ramadan compared to baseline (p < 0.05). The results suggest that Ramadan fasting may not adversely affect cognitive function in female athletes. PMID:26697263

  13. The Factors Affecting Bone Density in Cirrhosis

    PubMed Central

    Hajiabbasi, Asghar; Shafaghi, Afshin; Fayazi, Haniyeh Sadat; Shenavar Masooleh, Irandokht; Hedayati Emami, Mohammad Hassan; Ghavidel Parsa, Pooneh; Amir Maafi, Alireza

    2015-01-01

    Background: Bone loss is common in cirrhosis. However, the prevalence of osteopenia and osteoporosis has been heterogeneous in different reports. Reduction in bone formation with or without increase in bone resorption appears to be responsible for bone loss in these patients. Objectives: We aimed to investigate bone loss in patients with cirrhosis at different anatomical sites and key factors that might affect it. Patients and Methods: In this cross-sectional study, 97 patients with cirrhosis who were referred to Razi Hospital, Rasht, Iran, from 2008 to 2010, were studied. Cirrhosis was diagnosed using biopsy and/or clinical and paraclinical findings. Bone mineral densitometry was done in L2 through L4 lumbar spine (LS) and femoral neck (FN), using dual-energy X-ray absorptiometry (DEXA) (QDR 1000, Hologic DEXA Inc, Waltham, Massachusetts, the United States). Statistical analysis was performed using SPSS 18. A P value < 0.05 was considered statistically significant. Results: A total of 97 patients with cirrhosis (55.7% male) and the mean age of 51 ± 13 years and median body mass index (BMI) of 22.7 kg/m2 were recruited over a two-year period. Etiologies of cirrhosis were hepatitis C (40.2%), hepatitis B (26.8%), cryptogenic (21.6%), and other causes (11.4%). Child A, B, and C, were seen in 16.5%, 47.4%, and 36.1% of patients, respectively. The DEXA results were abnormal in 78.4% of our participants (osteopenia, 45.4%; osteoporosis, 33%). BMI and calculated glomerular filtration rate (GFRc) had moderate positive and Child score had moderate negative significant correlation with T score in both anatomical sites. There was no significant association between abnormal DEXA and the causes of cirrhosis. The univariate analysis showed that the risk of abnormal results in DEXA was significantly higher in those with low BMI, current smoking, higher Child score, and low GFRc; however, in multivariate analysis, the abnormal results were more frequent in those with lower

  14. Evidence for the Adverse Effect of Starvation on Bone Quality: A Review of the Literature

    PubMed Central

    Kueper, Janina; Beyth, Shaul; Liebergall, Meir; Kaplan, Leon; Schroeder, Josh E.

    2015-01-01

    Malnutrition and starvation's possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200–800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality. PMID:25810719

  15. Evidence for the adverse effect of starvation on bone quality: a review of the literature.

    PubMed

    Kueper, Janina; Beyth, Shaul; Liebergall, Meir; Kaplan, Leon; Schroeder, Josh E

    2015-01-01

    Malnutrition and starvation's possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200-800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality. PMID:25810719

  16. 47 CFR 73.4157 - Network signals which adversely affect affiliate broadcast service.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Network signals which adversely affect affiliate broadcast service. 73.4157 Section 73.4157 Telecommunication FEDERAL COMMUNICATIONS COMMISSION....4157 Network signals which adversely affect affiliate broadcast service. See Public Notice, FCC...

  17. 47 CFR 73.4157 - Network signals which adversely affect affiliate broadcast service.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 4 2011-10-01 2011-10-01 false Network signals which adversely affect affiliate broadcast service. 73.4157 Section 73.4157 Telecommunication FEDERAL COMMUNICATIONS COMMISSION....4157 Network signals which adversely affect affiliate broadcast service. See Public Notice, FCC...

  18. 47 CFR 73.4157 - Network signals which adversely affect affiliate broadcast service.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 4 2014-10-01 2014-10-01 false Network signals which adversely affect affiliate broadcast service. 73.4157 Section 73.4157 Telecommunication FEDERAL COMMUNICATIONS COMMISSION....4157 Network signals which adversely affect affiliate broadcast service. See Public Notice, FCC...

  19. 47 CFR 73.4157 - Network signals which adversely affect affiliate broadcast service.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 4 2013-10-01 2013-10-01 false Network signals which adversely affect affiliate broadcast service. 73.4157 Section 73.4157 Telecommunication FEDERAL COMMUNICATIONS COMMISSION....4157 Network signals which adversely affect affiliate broadcast service. See Public Notice, FCC...

  20. 47 CFR 73.4157 - Network signals which adversely affect affiliate broadcast service.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 4 2012-10-01 2012-10-01 false Network signals which adversely affect affiliate broadcast service. 73.4157 Section 73.4157 Telecommunication FEDERAL COMMUNICATIONS COMMISSION....4157 Network signals which adversely affect affiliate broadcast service. See Public Notice, FCC...

  1. Missing Out: Excessive Absenteeism Adversely Affects Elementary Reading Scores

    ERIC Educational Resources Information Center

    Hockert, Christine; Harrington, Sonja; Vaughn, Debra; Kelly, Kirk; Gooden, John

    2005-01-01

    This study was designed to answer the question "Does excessive absenteeism affect student academic achievement?" During the 2002-2003 academic year, 188 students attending grades 3 through 5 at an urban Tennessee elementary school with a high poverty level participated in the study. Demographic data were gathered to provide descriptive statistics…

  2. Root-Zone Glyphosate Exposure Adversely Affects Two Ditch Species

    PubMed Central

    Saunders, Lyndsay E.; Koontz, Melissa B.; Pezeshki, Reza

    2013-01-01

    Glyphosate, one of the most applied herbicides globally, has been extensively studied for its effects on non-target organisms. In the field, following precipitation, glyphosate runs off into agricultural ditches where it infiltrates into the soil and thus may encounter the roots of vegetation. These edge-of-field ditches share many characteristics with wetlands, including the ability to reduce loads of anthropogenic chemicals through uptake, transformation, and retention. Different species within the ditches may have a differential sensitivity to exposure of the root zone to glyphosate, contributing to patterns of abundance of ruderal species. The present laboratory experiment investigated whether two species commonly found in agricultural ditches in southcentral United States were affected by root zone glyphosate in a dose-dependent manner, with the objective of identifying a sublethal concentration threshold. The root zone of individuals of Polygonum hydropiperoides and Panicum hemitomon were exposed to four concentrations of glyphosate. Leaf chlorophyll content was measured, and the ratio of aboveground biomass to belowground biomass and survival were quantified. The findings from this study showed that root zone glyphosate exposure negatively affected both species including dose-dependent reductions in chlorophyll content. P. hydropiperdoides showed the greatest negative response, with decreased belowground biomass allocation and total mortality at the highest concentrations tested. PMID:24833234

  3. Urban sprawl and you: how sprawl adversely affects worker health.

    PubMed

    Pohanka, Mary; Fitzgerald, Sheila

    2004-06-01

    Urban sprawl, once thought of as just an environmental issue, is currently gaining momentum as an emerging public health issue worthy of research and political attention. Characteristics seen in sprawling communities include increasing traffic volumes; inadequate public transportation; pedestrian unfriendly streets; and the division of businesses, shops, and homes. These characteristics can affect health in many ways. Greater air pollution contributes to higher asthma and other lung disorder rates. An increased dependence on the automobile encourages a more sedentary lifestyle and can potentially contribute to obesity. The increased danger and stress of long commutes can lead to more accidents, anxiety, and social isolation. Occupational health nurses can become involved by promoting physical activity in the workplace, creating programs for injury prevention and stress management, becoming involved in political smart growth measures, and educating and encouraging colleagues to become active in addressing this issue. PMID:15219110

  4. Obesity Adversely Affects Survival in Pancreatic Cancer Patients

    PubMed Central

    McWilliams, Robert R.; Matsumoto, Martha E.; Burch, Patrick A.; Kim, George P.; Halfdanarson, Thorvardur R.; de Andrade, Mariza; Reid-Lombardo, Kaye; Bamlet, William R.

    2010-01-01

    Purpose Higher body-mass index (BMI) has been implicated as a risk factor for developing pancreatic cancer, but its effect on survival has not been thoroughly investigated. We assessed the association of BMI with survival in a sample of pancreatic cancer patients and utilized epidemiologic and clinical information to understand the contribution of diabetes and hyperglycemia. Methods A survival analysis using Cox proportional hazards by usual adult BMI was performed on 1,861 unselected patients with pancreatic adenocarcinoma; analyses were adjusted for covariates that included clinical stage, age, and sex. Secondary analyses incorporated self reported diabetes and fasting blood glucose in the survival model. Results BMI as a continuous variable was inversely associated with survival from pancreatic adenocarcinoma [hazard ratio 1.019 for each increased unit of BMI (kg/m2), p < 0.001] after adjustment for age, stage, and sex. In analysis by National Institutes of Health BMI category, BMI of 30–34.99 kg/m2 (HR 1.14, 95% confidence interval 0.98–1.33), 35–39.99 kg/m2 (HR 1.32, 95% CI 1.08–1.62), and ≥40 (HR 1.60, 95% CI 1.26–2.04) were associated with decreased survival compared to normal BMI of 18,5–24.99 kg/m2 (overall trend test p<0.001). Fasting blood glucose and diabetes did not affect the results. Conclusions Higher BMI is associated with decreased survival in pancreatic cancer. Although the mechanism of this association remains undetermined, diabetes and hyperglycemia do not appear to account for the observed association. PMID:20665496

  5. Is Bone Tissue Really Affected by Swimming? A Systematic Review

    PubMed Central

    Gómez-Bruton, Alejandro; Gónzalez-Agüero, Alejandro; Gómez-Cabello, Alba; Casajús, José A.; Vicente-Rodríguez, Germán

    2013-01-01

    Background Swimming, a sport practiced in hypogravity, has sometimes been associated with decreased bone mass. Aim This systematic review aims to summarize and update present knowledge about the effects of swimming on bone mass, structure and metabolism in order to ascertain the effects of this sport on bone tissue. Methods A literature search was conducted up to April 2013. A total of 64 studies focusing on swimmers bone mass, structure and metabolism met the inclusion criteria and were included in the review. Results It has been generally observed that swimmers present lower bone mineral density than athletes who practise high impact sports and similar values when compared to sedentary controls. However, swimmers have a higher bone turnover than controls resulting in a different structure which in turn results in higher resistance to fracture indexes. Nevertheless, swimming may become highly beneficial regarding bone mass in later stages of life. Conclusion Swimming does not seem to negatively affect bone mass, although it may not be one of the best sports to be practised in order to increase this parameter, due to the hypogravity and lack of impact characteristic of this sport. Most of the studies included in this review showed similar bone mineral density values in swimmers and sedentary controls. However, swimmers present a higher bone turnover than sedentary controls that may result in a stronger structure and consequently in a stronger bone. PMID:23950908

  6. Alteration of proteoglycan sulfation affects bone growth and remodeling

    PubMed Central

    Gualeni, Benedetta; de Vernejoul, Marie-Christine; Marty-Morieux, Caroline; De Leonardis, Fabio; Franchi, Marco; Monti, Luca; Forlino, Antonella; Houillier, Pascal; Rossi, Antonio; Geoffroy, Valerie

    2013-01-01

    Diastrophic dysplasia (DTD) is a chondrodysplasia caused by mutations in the SLC26A2 gene, leading to reduced intracellular sulfate pool in chondrocytes, osteoblasts and fibroblasts. Hence, proteoglycans are undersulfated in the cartilage and bone of DTD patients. To characterize the bone phenotype of this skeletal dysplasia we used the Slc26a2 knock-in mouse (dtd mouse), that was previously validated as an animal model of DTD in humans. X-rays, bone densitometry, static and dynamic histomorphometry, and in vitro studies revealed a primary bone defect in the dtd mouse model. We showed in vivo that this primary bone defect in dtd mice is due to decreased bone accrual associated with a decreased trabecular and periosteal appositional rate at the cell level in one month-old mice. Although the osteoclast number evaluated by histomorphometry was not different in dtd compared to wild-type mice, urine analysis of deoxypyridinoline cross-links and serum levels of type I collagen C-terminal telopeptides showed a higher resorption rate in dtd mice compared to wild-type littermates. Electron microscopy studies showed that collagen fibrils in bone were thinner and less organized in dtd compared to wild-type mice. These data suggest that the low bone mass observed in mutant mice could possibly be linked to the different bone matrix compositions/organizations in dtd mice triggering changes in osteoblast and osteoclast activities. Overall, these results suggest that proteoglycan undersulfation not only affects the properties of hyaline cartilage, but can also lead to unbalanced bone modeling and remodeling activities, demonstrating the importance of proteoglycan sulfation in bone homeostasis. PMID:23369989

  7. Adverse Biological Effect of TiO₂ and Hydroxyapatite Nanoparticles Used in Bone Repair and Replacement.

    PubMed

    Wang, Jiangxue; Wang, Liting; Fan, Yubo

    2016-01-01

    The adverse biological effect of nanoparticles is an unavoidable scientific problem because of their small size and high surface activity. In this review, we focus on nano-hydroxyapatite and TiO₂ nanoparticles (NPs) to clarify the potential systemic toxicological effect and cytotoxic response of wear nanoparticles because they are attractive materials for bone implants and are widely investigated to promote the repair and reconstruction of bone. The wear nanoparticles would be prone to binding with proteins to form protein-particle complexes, to interacting with visible components in the blood including erythrocytes, leukocytes, and platelets, and to being phagocytosed by macrophages or fibroblasts to deposit in the local tissue, leading to the formation of fibrous local pseudocapsules. These particles would also be translocated to and disseminated into the main organs such as the lung, liver and spleen via blood circulation. The inflammatory response, oxidative stress, and signaling pathway are elaborated to analyze the potential toxicological mechanism. Inhibition of the oxidative stress response and signaling transduction may be a new therapeutic strategy for wear debris-mediated osteolysis. Developing biomimetic materials with better biocompatibility is our goal for orthopedic implants. PMID:27231896

  8. Osseous healing with a composite of allograft and demineralized bone matrix: adverse effects of smoking.

    PubMed

    Ziran, Bruce H; Hendi, Pooneh; Smith, Wade R; Westerheide, Kenneth; Agudelo, Juan F

    2007-04-01

    We report on our use of a composite graft of lyophilized cancellous allogenic chips and demineralized bone matrix (DBM; Grafton; Osteotech, Eatontown, NJ) to manage traumatic osseous defects and nonunions. Data were prospectively collected from all patients who received this composite bone graft between 1996 and 2000. Only acute fractures with bone loss resulting in a uncontained defect and atrophic non-unions were included in the present study. Demographic data and complications related to composite use, tobacco use, and other comorbidities that could affect healing were evaluated. One hundred seven patients (112 bone graft sites) were followed up for a mean of 32 months (range, 12-60 months). Graft sites included the forearm, femur and tibia. Of the 112 patients, there were 56 smokers (25 non-unions and 31 fractures) and 56 non-smokers (28 fractures and 28 non-unions). Healing occured in 38/56 smokers compared with 49/56 non-smokers. In failed cases, smoking was characteristic in 7/9 non-unions and 11/16 fractures. There were 26 acute uncontained injuries, 29 acute contained defects, and 67 nonunions. Grafting sites were radius/ulna (13 cases), humerus (17), femur (31), and tibia/fibula (51). Significant comorbidities were diabetes mellitus (4 cases), fungal osteomyelitis (1), and pulmonary alveolar proteinosis (1). Eight (73%) of the 11 patients with graft failure had a significant smoking history. This composite graft is an option for managing osseous defects and nonunions traditionally treated with autologous bone grafting but should be used with caution when treating patients who are smokers. PMID:17515188

  9. Clinical factors affecting pathological fracture and healing of unicameral bone cysts

    PubMed Central

    2014-01-01

    Background Unicameral bone cyst (UBC) is the most common benign lytic bone lesion seen in children. The aim of this study is to investigate clinical factors affecting pathological fracture and healing of UBC. Methods We retrospectively reviewed 155 UBC patients who consulted Nagoya musculoskeletal oncology group hospitals in Japan. Sixty of the 155 patients had pathological fracture at presentation. Of 141 patients with follow-up periods exceeding 6 months, 77 were followed conservatively and 64 treated by surgery. Results The fracture risk was significantly higher in the humerus than other bones. In multivariate analysis, ballooning of bone, cyst in long bone, male sex, thin cortical thickness and multilocular cyst were significant adverse prognostic factors for pathological fractures at presentation. The healing rates were 30% and 83% with observation and surgery, respectively. Multivariate analysis revealed that fracture at presentation and history of biopsy were good prognostic factors for healing of UBC in patients under observation. Conclusion The present results suggest that mechanical disruption of UBC such as fracture and biopsy promotes healing, and thus watchful waiting is indicated in these patients, whereas patients with poor prognostic factors for fractures should be considered for surgery. PMID:24884661

  10. High vitamin D3 diet administered during active colitis negatively affects bone metabolism in an adoptive T cell transfer model

    PubMed Central

    Larmonier, C. B.; McFadden, R.-M. T.; Hill, F. M.; Schreiner, R.; Ramalingam, R.; Besselsen, D. G.; Ghishan, F. K.

    2013-01-01

    Decreased bone mineral density (BMD) represents an extraintestinal complication of inflammatory bowel disease (IBD). Vitamin D3 has been considered a viable adjunctive therapy in IBD. However, vitamin D3 plays a pleiotropic role in bone modeling and regulates the bone formation-resorption balance, depending on the physiological environment, and supplementation during active IBD may have unintended consequences. We evaluated the effects of vitamin D3 supplementation during the active phase of disease on colonic inflammation, BMD, and bone metabolism in an adoptive IL-10−/− CD4+ T cell transfer model of chronic colitis. High-dose vitamin D3 supplementation for 12 days during established disease had negligible effects on mucosal inflammation. Plasma vitamin D3 metabolites correlated with diet, but not disease, status. Colitis significantly reduced BMD. High-dose vitamin D3 supplementation did not affect cortical bone but led to a further deterioration of trabecular bone morphology. In mice fed a high vitamin D3 diet, colitis more severely impacted bone formation markers (osteocalcin and bone alkaline phosphatase) and increased bone resorption markers, ratio of receptor activator of NF-κB ligand to osteoprotegrin transcript, plasma osteoprotegrin level, and the osteoclast activation marker tartrate-resistant acid phosphatase (ACp5). Bone vitamin D receptor expression was increased in mice with chronic colitis, especially in the high vitamin D3 group. Our data suggest that vitamin D3, at a dose that does not improve inflammation, has no beneficial effects on bone metabolism and density during active colitis or may adversely affect BMD and bone turnover. These observations should be taken into consideration in the planning of further clinical studies with high-dose vitamin D3 supplementation in patients with active IBD. PMID:23639807

  11. 41 CFR 102-78.40 - What responsibilities do Federal agencies have when an undertaking adversely affects a historic...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... guidance on the protection of historic and cultural properties in 36 CFR part 800. ... Federal agencies have when an undertaking adversely affects a historic or cultural property? 102-78.40...-78.40 What responsibilities do Federal agencies have when an undertaking adversely affects a...

  12. 50 CFR 402.45 - Alternative consultation on FIFRA actions that are not likely to adversely affect listed species...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... that are not likely to adversely affect listed species or critical habitat. 402.45 Section 402.45... habitat. (a) Consultation obligations for FIFRA actions that are not likely to adversely affect listed species or critical habitat when alternative consultation agreement is in effect. If EPA and the...

  13. 50 CFR 402.45 - Alternative consultation on FIFRA actions that are not likely to adversely affect listed species...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... that are not likely to adversely affect listed species or critical habitat. 402.45 Section 402.45... habitat. (a) Consultation obligations for FIFRA actions that are not likely to adversely affect listed species or critical habitat when alternative consultation agreement is in effect. If EPA and the...

  14. 50 CFR 402.45 - Alternative consultation on FIFRA actions that are not likely to adversely affect listed species...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... that are not likely to adversely affect listed species or critical habitat. 402.45 Section 402.45... habitat. (a) Consultation obligations for FIFRA actions that are not likely to adversely affect listed species or critical habitat when alternative consultation agreement is in effect. If EPA and the...

  15. Genetic polymorphisms affect efficacy and adverse drug reactions of DMARDs in rheumatoid arthritis.

    PubMed

    Zhang, Ling Ling; Yang, Sen; Wei, Wei; Zhang, Xue Jun

    2014-11-01

    Disease-modifying antirheumatic drugs (DMARDs) and biological agents are critical in preventing the severe complications of rheumatoid arthritis (RA). However, the outcome of treatment with these drugs in RA patients is quite variable and unpredictable. Drug-metabolizing enzymes (dihydrofolate reductase, cytochrome P450 enzymes, N-acetyltransferases, etc.), drug transporters (ATP-binding cassette transporters), and drug targets (tumor necrosis factor-α receptors) are coded for by variant alleles. These gene polymorphisms may influence the pharmacokinetics, pharmacodynamics, and side effects of medicines. The cause for differences in efficacy and adverse drug reactions may be genetic variation in drug metabolism among individuals. Polymorphisms in drug transporter genes may change the distribution and excretion of medicines, and the sensitivity of the targets to drugs is strongly influenced by genetic variations. In this article, we review the genetic polymorphisms that affect the efficacy of DMARDs or the occurrence of adverse drug reactions associated with DMARDs in RA. PMID:25144752

  16. Family Adversity and Autonomic Reactivity Association With Immune Changes in HIV-Affected School Children

    PubMed Central

    Thomas, Melanie; Wara, Diane; Saxton, Katherine; Truskier, Mary; Chesney, Margaret; Boyce, W. Thomas

    2013-01-01

    Objective To explore whether primary school entry is associated with changes in immune system parameters in HIV-affected children. HIV-affected children are vulnerable to psychosocial stressors, regardless of their own HIV serological status. Methods Data from 38 HIV+ and 29 HIV− children born to seropositive women were obtained before and after school entry. Measures included family adversity questionnaires, autonomic nervous system (ANS) reactivity (based on mean arterial responses to challenge tasks), and enumerative and functional changes in peripheral blood immune parameters. Results In comparison to children who were HIV−, children who were HIV+ at baseline had fewer CD4+ T lymphocytes (M = 916 vs. 1206 cells/mm3 × 103; F = 7.8, p = .007), more CD8+ cells (M = 1046 vs. 720 cells/mm3 ×103; F = 7.98, p = .006), and diminished NK cell cytotoxicity (M =−.29 vs. .41; F = 8.87, p = .004). School entry was associated with changes in immune parameters, but HIV status was not associated with the magnitude of changes. Changes in immune parameters following school entry were associated with family stress and pre school entry ANS reactivity. Highly ANS reactive children had either the greatest increase in CD8+ cells following school entry or the greatest decrease, depending upon reported levels of family adversity (B = 215.35; t = 3.74, p < .001). Changes in functional immune assays were significantly associated with the interactions between HIV status and ANS reactivity. Conclusions These results suggest that autonomic reactivity is associated with increased immunological sensitivity to adverse or challenging social contexts among children affected by HIV. PMID:23766380

  17. 42 CFR 137.435 - Will an appeal adversely affect the Indian Tribe's rights in other compact, funding negotiations...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... rights in other compact, funding negotiations, or construction project agreement? 137.435 Section 137.435... another compact, funding agreement, or construction project agreement. ... appeal adversely affect the Indian Tribe's rights in other compact, funding negotiations, or...

  18. Cannula implantation into the lateral ventricle does not adversely affect recognition or spatial working memory.

    PubMed

    Seyer, Benjamin; Pham, Vi; Albiston, Anthony L; Chai, Siew Yeen

    2016-08-15

    Indwelling cannulas are often used to deliver pharmacological agents into the lateral ventricles of the brain to study their effects on memory and learning, yet little is known about the possible adverse effects of the cannulation itself. In this study, the effect of implanting an indwelling cannula into the right lateral ventricle was examined with respect to cognitive function and tissue damage in rats. Specifically, the cannula passed through sections of the primary motor (M1) and somatosensory hind limb (S1HL) cortices. One week following implantation, rats were impaired on the rotarod task, implying a deficit in fine motor control, likely caused by the passage of the cannula through the aforementioned cortical regions. Importantly, neither spatial working nor recognition memory was adversely affected. Histological examination showed immune cell activation only in the area immediately surrounding the cannulation site and not spreading to other brain regions. Both GFAP and CD-11b mRNA expression was elevated in the area immediately surrounding the cannulation site, but not in the contralateral hemisphere or the hippocampus. Neither of the inflammatory cytokines, TNF-α or IL-6, were upregulated in any region. These results show that cannulation into the lateral ventricle does not impair cognition and indicates that nootropic agents delivered via this method are enhancing normal memory rather than rescuing deficits caused by the surgery procedure. PMID:27345383

  19. Long-term adverse outcomes in survivors of childhood bone sarcoma: the British Childhood Cancer Survivor Study

    PubMed Central

    Fidler, M M; Frobisher, C; Guha, J; Wong, K; Kelly, J; Winter, D L; Sugden, E; Duncan, R; Whelan, J; Reulen, R C; Hawkins, M M

    2015-01-01

    Background: With improved survival, more bone sarcoma survivors are approaching middle age making it crucial to investigate the late effects of their cancer and its treatment. We investigated the long-term risks of adverse outcomes among 5-year bone sarcoma survivors within the British Childhood Cancer Survivor Study. Methods: Cause-specific mortality and risk of subsequent primary neoplasms (SPNs) were investigated for 664 bone sarcoma survivors. Use of health services, health and marital status, alcohol and smoking habits, and educational qualifications were investigated for survivors who completed a questionnaire. Results: Survivors were seven times more likely to experience all-cause mortality than expected, and there were substantial differences in risk depending on tumour type. Beyond 25 years follow-up the risk of dying from all-causes was comparable to the general population. This is in contrast to dying before 25 years where the risk was 12.7-fold that expected. Survivors were also four times more likely to develop a SPN than expected, where the excess was restricted to 5–24 years post diagnosis. Increased health-care usage and poor health status were also found. Nonetheless, for some psychosocial outcomes survivors were better off than expected. Conclusions: Up to 25 years after 5-year survival, bone sarcoma survivors are at substantial risk of death and SPNs, but this is greatly reduced thereafter. As 95% of all excess deaths before 25 years follow-up were due to recurrences and SPNs, increased monitoring of survivors could prevent mortality. Furthermore, bone and breast SPNs should be a particular concern. Since there are variations in the magnitude of excess risk depending on the specific adverse outcome under investigation and whether the survivors were initially diagnosed with osteosarcoma or Ewing sarcoma, risks need to be assessed in relation to these factors. These findings should provide useful evidence for risk stratification and updating

  20. Bone development in black ducks as affected by dietary toxaphene

    USGS Publications Warehouse

    Mehrle, P.M.; Finley, M.T.; Ludke, J.L.; Mayer, F.L.; Kaiser, T.E.

    1979-01-01

    Black ducks, Anas rubripes, were exposed to dietary toxaphene concentrations of 0, 10, or 50 μg/g of food for 90 days prior to laying and through the reproductive season. Toxaphene did not affect reproduction or survival, but reduced growth and impaired backbone development in ducklings. Collagen, the organic matrix of bone, was decreased significantly in cervical vertebrae of ducklings fed 50 μg/g, and calcium conentrations increased in vertebrae of ducklings fed 10 or 50 μg/g. The effects of toxaphene were observed only in female ducklings. In contrast to effects on vertebrae, toxaphene exposure did not alter tibia development. Toxaphene residues in carcasses of these ducklings averaged slightly less than the dietary levels.

  1. Factors Affecting Bone Mineral Density in Adults with Cerebral Palsy

    PubMed Central

    Yoon, Young Kwon; Kim, Ae Ryoung; Kim, On Yoo; Lee, Kilchan; Suh, Young Joo

    2012-01-01

    Objective To clarify factors affecting bone mineral density (BMD) in adults with cerebral palsy (CP). Method Thirty-five patients with CP participated in this study. Demographic data including gender, age, body mass index (BMI), subtype according to neuromotor type and topographical distribution, ambulatory function, and functional independence measure (FIM) were investigated. The BMD of the lumbar spine and femur were measured using Dual-energy X-ray absorptiometry, and the factors affecting BMD were analyzed. Results The BMD had no significant association with factors such as gender, age, and subtype in adults with CP. However, BMI was significantly correlated with the BMD of lumbar spine and femur (p<0.05). The FIM score was also positively correlated with the BMD of femur (p<0.05). Moreover, CP patients with higher ambulatory function had significantly higher BMD of femur (p<0.05). Conclusion These findings suggest that BMI and functional levels such as FIM and ambulatory function can affect BMD in adults with CP. The results might be used as basic data, suggesting the importance of treatment including weight bearing exercise and gait training in adults with CP. PMID:23342308

  2. Factors Affecting the Timing of Signal Detection of Adverse Drug Reactions.

    PubMed

    Hashiguchi, Masayuki; Imai, Shungo; Uehara, Keiko; Maruyama, Junya; Shimizu, Mikiko; Mochizuki, Mayumi

    2015-01-01

    We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2-10 months for known ADRs and 19-44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0-122.5 days and 185.5-306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release. PMID:26641634

  3. Sexually Dimorphic Responses to Early Adversity: Implications for Affective Problems and Autism Spectrum Disorder

    PubMed Central

    Davis, Elysia Poggi; Pfaff, Donald

    2014-01-01

    During gestation, development proceeds at a pace that is unmatched by any other stage of the lifecycle. For these reason the human fetus is particularly susceptible not only to organizing influences, but also to pathogenic disorganizing influences. Growing evidence suggests that exposure to prenatal adversity leads to neurological changes that underlie lifetime risks for mental illness. Beginning early in gestation, males and females show differential developmental trajectories and responses to stress. It is likely that sex-dependent organization of neural circuits during the fetal period influences differential vulnerability to mental health problems. We consider in this review evidence that sexually dimorphic responses to early life stress are linked to two developmental disorders: affective problems (greater female prevalence) and autism spectrum disorder (greater male prevalence). Recent prospective studies illustrating the neurodevelopmental consequences of fetal exposure to stress and stress hormones for males and females are considered here. Plausible biological mechanisms including the role of the sexually differentiated placenta are discussed. We consider in this review evidence that sexually dimorphic responses to early life stress are linked to two sets of developmental disorders: affective problems (greater female prevalence) and autism spectrum disorders (greater male prevalence). PMID:25038479

  4. Suppression of Autophagy in Osteocytes Does Not Modify the Adverse Effects of Glucocorticoids on Cortical Bone

    PubMed Central

    Piemontese, Marilina; Onal, Melda; Xiong, Jinhu; Wang, Yiying; Almeida, Maria; Thostenson, Jeff D.; Weinstein, Robert S.; Manolagas, Stavros C.; O’Brien, Charles A.

    2015-01-01

    Glucocorticoid excess decreases bone mass and strength in part by acting directly on osteoblasts and osteocytes, but the mechanisms remain unclear. Macroautophagy (herein referred to as autophagy) is a lysosome-based recycling pathway that promotes the turnover of intracellular components and can promote cell function and survival under stressful conditions. Recent studies have shown that glucocorticoids stimulate autophagy in osteocytes, suggesting that autophagy may oppose the negative actions of glucocorticoids on this cell type. To address this possibility, we compared the impact of prednisolone administration on the skeletons of adult mice in which autophagy was suppressed in osteocytes, via deletion of Atg7 with a Dmp1-Cre transgene, to their control littermates. In control mice, prednisolone increased autophagic flux in osteocyte-enriched bone as measured by LC3 conversion, but this change did not occur in the mice lacking Atg7 in osteocytes. Nonetheless, prednisolone reduced femoral cortical thickness, increased cortical porosity, and reduced bone strength to similar extents in mice with and without autophagy in osteocytes. Prednisolone also suppressed osteoblast number and bone formation in the cancellous bone of control mice. As shown previously, Atg7 deletion in osteocytes reduced osteoblast number and bone formation in cancellous bone, but these parameters were not further reduced by prednisolone administration. In cortical bone, prednisolone elevated osteoclast number to a similar extent in both genotypes. Taken together, these results demonstrate that although glucocorticoids stimulate autophagy in osteocytes, suppression of autophagy in this cell type does not worsen the negative impact of glucocorticoids on the skeleton. PMID:25700544

  5. Adynamic Bone Decreases Bone Toughness During Aging by Affecting Mineral and Matrix.

    PubMed

    Ng, Adeline H; Omelon, Sidney; Variola, Fabio; Allo, Bedilu; Willett, Thomas L; Alman, Benjamin A; Grynpas, Marc D

    2016-02-01

    Adynamic bone is the most frequent type of bone lesion in patients with chronic kidney disease; long-term use of antiresorptive therapy may also lead to the adynamic bone condition. The hallmark of adynamic bone is a loss of bone turnover, and a major clinical concern of adynamic bone is diminished bone quality and an increase in fracture risk. Our current study aims to investigate how bone quality changes with age in our previously established mouse model of adynamic bone. Young and old mice (4 months old and 16 months old, respectively) were used in this study. Col2.3Δtk (DTK) mice were treated with ganciclovir and pamidronate to create the adynamic bone condition. Bone quality was evaluated using established techniques including bone histomorphometry, microcomputed tomography, quantitative backscattered electron imaging, and biomechanical testing. Changes in mineral and matrix properties were examined by powder X-ray diffraction and Raman spectroscopy. Aging controls had a natural decline in bone formation and resorption with a corresponding deterioration in trabecular bone structure. Bone turnover was severely blunted at all ages in adynamic animals, which preserved trabecular bone loss normally associated with aging. However, the preservation of trabecular bone mass and structure in old adynamic mice did not rescue deterioration of bone mechanical properties. There was also a decrease in cortical bone toughness in old adynamic mice that was accompanied by a more mature collagen matrix and longer bone crystals. Little is known about the effects of metabolic bone disease on bone fracture resistance. We observed an age-related decrease in bone toughness that was worsened by the adynamic condition, and this decrease may be due to material level changes at the tissue level. Our mouse model may be useful in the investigation of the mechanisms involved in fractures occurring in elderly patients on antiresorptive therapy who have very low bone turnover. PMID:26332924

  6. 42 CFR 137.445 - Will an immediate reassumption appeal adversely affect the Self-Governance Tribe's rights in...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... affect the Self-Governance Tribe's rights in other self-governance negotiations? 137.445 Section 137.445..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Appeals Appeals of An Immediate Reassumption of A Self-Governance Program § 137.445 Will an immediate reassumption appeal adversely affect...

  7. 42 CFR 137.445 - Will an immediate reassumption appeal adversely affect the Self-Governance Tribe's rights in...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... affect the Self-Governance Tribe's rights in other self-governance negotiations? 137.445 Section 137.445..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Appeals Appeals of An Immediate Reassumption of A Self-Governance Program § 137.445 Will an immediate reassumption appeal adversely affect...

  8. 42 CFR 137.445 - Will an immediate reassumption appeal adversely affect the Self-Governance Tribe's rights in...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... affect the Self-Governance Tribe's rights in other self-governance negotiations? 137.445 Section 137.445..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Appeals Appeals of An Immediate Reassumption of A Self-Governance Program § 137.445 Will an immediate reassumption appeal adversely affect...

  9. 42 CFR 137.445 - Will an immediate reassumption appeal adversely affect the Self-Governance Tribe's rights in...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... affect the Self-Governance Tribe's rights in other self-governance negotiations? 137.445 Section 137.445..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Appeals Appeals of An Immediate Reassumption of A Self-Governance Program § 137.445 Will an immediate reassumption appeal adversely affect...

  10. 42 CFR 137.445 - Will an immediate reassumption appeal adversely affect the Self-Governance Tribe's rights in...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... affect the Self-Governance Tribe's rights in other self-governance negotiations? 137.445 Section 137.445..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Appeals Appeals of An Immediate Reassumption of A Self-Governance Program § 137.445 Will an immediate reassumption appeal adversely affect...

  11. Early Life in a Barren Environment Adversely Affects Spatial Cognition in Laying Hens (Gallus gallus domesticus)

    PubMed Central

    Tahamtani, Fernanda M.; Nordgreen, Janicke; Nordquist, Rebecca E.; Janczak, Andrew M.

    2015-01-01

    Spatial cognition in vertebrates is adversely affected by a lack of environmental complexity during early life. However, to our knowledge, no previous studies have tested the effect of early exposure to varying degrees of environmental complexity on specific components of spatial cognition in chickens. There are two main rearing systems for laying hens in the EU: aviaries and cages. These two systems differ from one another in environmental complexity. The aim of the present study was to test the hypothesis that rearing in a barren cage environment relative to a complex aviary environment causes long-lasting deficits in the ability to perform spatial tasks. For this purpose, 24 white Dekalb laying hens, half of which had been reared in an aviary system and the other half in a conventional cage system, were tested in a holeboard task. Birds from both treatment groups learnt the task; however, the cage-reared hens required more time to locate rewards and had poorer levels of working memory. The latter finding supports the hypothesis that rearing in a barren environment causes long-term impairment of short-term memory in chickens. PMID:26664932

  12. Exposing physicians to reduced residency work hours did not adversely affect patient outcomes after residency.

    PubMed

    Jena, Anupam B; Schoemaker, Lena; Bhattacharya, Jay

    2014-10-01

    In 2003, work hours for physicians-in-training (residents) were capped by regulation at eighty hours per week, leading to the hotly debated but unexplored issue of whether physicians today are less well trained as a result of these work-hour reforms. Using a unique database of nearly all hospitalizations in Florida during 2000-09 that were linked to detailed information on the medical training history of the physician of record for each hospitalization, we studied whether hospital mortality and patients' length-of-stay varied according to the number of years a physician was exposed to the 2003 duty-hour regulations during his or her residency. We examined this database of practicing Florida physicians, using a difference-in-differences analysis that compared trends in outcomes of junior physicians (those with one-year post-residency experience) pre- and post-2003 to a control group of senior physicians (those with ten or more years of post-residency experience) who were not exposed to these reforms during their residency. We found that the duty-hour reforms did not adversely affect hospital mortality and length-of-stay of patients cared for by new attending physicians who were partly or fully exposed to reduced duty hours during their own residency. However, assessment of the impact of the duty-hour reforms on other clinical outcomes is needed. PMID:25288430

  13. Delay of Treatment Initiation Does Not Adversely Affect Survival Outcome in Breast Cancer

    PubMed Central

    Yoo, Tae-Kyung; Han, Wonshik; Moon, Hyeong-Gon; Kim, Jisun; Lee, Jun Woo; Kim, Min Kyoon; Lee, Eunshin; Kim, Jongjin; Noh, Dong-Young

    2016-01-01

    Purpose Previous studies examining the relationship between time to treatment and survival outcome in breast cancer have shown inconsistent results. The aim of this study was to analyze the overall impact of delay of treatment initiation on patient survival and to determine whether certain subgroups require more prompt initiation of treatment. Materials and Methods This study is a retrospective analysis of stage I-III patients who were treated in a single tertiary institution between 2005 and 2008. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to evaluate the impact of interval between diagnosis and treatment initiation in breast cancer and various subgroups. Results A total of 1,702 patients were included. Factors associated with longer delay of treatment initiation were diagnosis at another hospital, medical comorbidities, and procedures performed before admission for surgery. An interval between diagnosis and treatment initiation as a continuous variable or with a cutoff value of 15, 30, 45, and 60 days had no impact on disease-free survival (DFS). Subgroup analyses for hormone-responsiveness, triple-negative breast cancer, young age, clinical stage, and type of initial treatment showed no significant association between longer delay of treatment initiation and DFS. Conclusion Our results show that an interval between diagnosis and treatment initiation of 60 days or shorter does not appear to adversely affect DFS in breast cancer. PMID:26511801

  14. Neonicotinoid clothianidin adversely affects insect immunity and promotes replication of a viral pathogen in honey bees.

    PubMed

    Di Prisco, Gennaro; Cavaliere, Valeria; Annoscia, Desiderato; Varricchio, Paola; Caprio, Emilio; Nazzi, Francesco; Gargiulo, Giuseppe; Pennacchio, Francesco

    2013-11-12

    Large-scale losses of honey bee colonies represent a poorly understood problem of global importance. Both biotic and abiotic factors are involved in this phenomenon that is often associated with high loads of parasites and pathogens. A stronger impact of pathogens in honey bees exposed to neonicotinoid insecticides has been reported, but the causal link between insecticide exposure and the possible immune alteration of honey bees remains elusive. Here, we demonstrate that the neonicotinoid insecticide clothianidin negatively modulates NF-κB immune signaling in insects and adversely affects honey bee antiviral defenses controlled by this transcription factor. We have identified in insects a negative modulator of NF-κB activation, which is a leucine-rich repeat protein. Exposure to clothianidin, by enhancing the transcription of the gene encoding this inhibitor, reduces immune defenses and promotes the replication of the deformed wing virus in honey bees bearing covert infections. This honey bee immunosuppression is similarly induced by a different neonicotinoid, imidacloprid, but not by the organophosphate chlorpyriphos, which does not affect NF-κB signaling. The occurrence at sublethal doses of this insecticide-induced viral proliferation suggests that the studied neonicotinoids might have a negative effect at the field level. Our experiments uncover a further level of regulation of the immune response in insects and set the stage for studies on neural modulation of immunity in animals. Furthermore, this study has implications for the conservation of bees, as it will contribute to the definition of more appropriate guidelines for testing chronic or sublethal effects of pesticides used in agriculture. PMID:24145453

  15. High fat diet enriched with saturated, but not monounsaturated fatty acids adversely affects femur, and both diets increase calcium absorption in older female mice.

    PubMed

    Wang, Yang; Dellatore, Peter; Douard, Veronique; Qin, Ling; Watford, Malcolm; Ferraris, Ronaldo P; Lin, Tiao; Shapses, Sue A

    2016-07-01

    Diet induced obesity has been shown to reduce bone mineral density (BMD) and Ca absorption. However, previous experiments have not examined the effect of high fat diet (HFD) in the absence of obesity or addressed the type of dietary fatty acids. The primary objective of this study was to determine the effects of different types of high fat feeding, without obesity, on fractional calcium absorption (FCA) and bone health. It was hypothesized that dietary fat would increase FCA and reduce BMD. Mature 8-month-old female C57BL/6J mice were fed one of three diets: a HFD (45% fat) enriched either with monounsaturated fatty acids (MUFAs) or with saturated fatty acids (SFAs), and a normal fat diet (NFD; 10% fat). Food consumption was controlled to achieve a similar body weight gain in all groups. After 8wk, total body bone mineral content and BMD as well as femur total and cortical volumetric BMD were lower in SFA compared with NFD groups (P<.05). In contrast, femoral trabecular bone was not affected by the SFAs, whereas MUFAs increased trabecular volume fraction and thickness. The rise over time in FCA was greater in mice fed HFD than NFD and final FCA was higher with HFD (P<.05). Intestinal calbindin-D9k gene and hepatic cytochrome P450 2r1 protein levels were higher with the MUFA than the NFD diet (P<.05). In conclusion, HFDs elevated FCA overtime; however, an adverse effect of HFD on bone was only observed in the SFA group, while MUFAs show neutral or beneficial effects. PMID:27262536

  16. Probabilities of adverse weather affecting transport in Europe: climatology and scenarios up to the 2050s

    NASA Astrophysics Data System (ADS)

    Vajda, A.; Tuomenvirta, H.; Jokinen, P.; Luomaranta, A.; Makkonen, L.; Tikanmäki, M.; Groenemeijer, P.; Saarikivi, P.; Michaelides, S.; Papadakis, M.; Tymvios, F.; Athanasatos, S.

    2012-04-01

    This paper provides the first comprehensive climatology of the adverse and extreme weather events affecting the European transport system by estimating the frequency (or probability) of phenomena for the present climate (1971-2000) and an overview of the projected changes in some of these extremes in the future climate until the 2050s. The research was carried out within the framework of the EWENT Project that addresses the European Union (EU) policies and strategies related to climate change, with a particular focus on extreme weather impacts on the EU transportation system. This project is funded by the Seventh Framework Programme (Transports, call ID FPT7-TPT-2008-RTD-1). The analyzed phenomena are wind, snow, blizzards, heavy precipitation, cold spells and heat waves. In addition, reduced visibility conditions determined by fog and dust events, small-scale phenomena affecting the transport system, such as thunderstorms, lightning, large hail and tornadoes and events damaging infrastructure of the transport system, have been considered. Frequency and probability analysis of past and present ex¬tremes were performed using observational and atmospheric reanalysis data. Future changes in the probability of severe events were assessed based on six regional climate model simulations produced in the FP6 ENSEMBLES project (http://www.ensembles-eu.org/). To facilitate the assessment of impacts and consequences of extreme phenomena on a continental level, the WP2 Deliverable introduces a regionalization of the European extreme phenomena, defining the climate zones with similarities in extreme phenomena. The projected changes as well as large natural variability in weather extremes on the transportation network will have impacts of both signs. The decline of extreme cold and snowfall over most of the continent implies a positive impact on road, rail, inland water and air transportation, e.g., by reducing snow removal. However, even with a general decreasing trend in

  17. 41 CFR 102-78.40 - What responsibilities do Federal agencies have when an undertaking adversely affects a historic...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... guidance on the protection of historic and cultural properties in 36 CFR part 800. ... Federal agencies have when an undertaking adversely affects a historic or cultural property? 102-78.40... (Continued) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 78-HISTORIC PRESERVATION Historic Preservation §...

  18. 25 CFR 900.244 - Will an Indian tribe or tribal organization's retrocession adversely affect funding available for...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false Will an Indian tribe or tribal organization's retrocession adversely affect funding available for the retroceded program? 900.244 Section 900.244 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR, AND INDIAN HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES CONTRACTS UNDER THE...

  19. 50 CFR 402.45 - Alternative consultation on FIFRA actions that are not likely to adversely affect listed species...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S... that are not likely to adversely affect listed species or critical habitat. 402.45 Section...

  20. 50 CFR 402.45 - Alternative consultation on FIFRA actions that are not likely to adversely affect listed species...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S... that are not likely to adversely affect listed species or critical habitat. 402.45 Section...

  1. Pyridoxine deficiency affects biomechanical properties of chick tibial bone

    NASA Technical Reports Server (NTRS)

    Masse, P. G.; Rimnac, C. M.; Yamauchi, M.; Coburn, S. P.; Rucker, R. B.; Howell, D. S.; Boskey, A. L.

    1996-01-01

    The mechanical integrity of bone is dependent on the bone matrix, which is believed to account for the plastic deformation of the tissue, and the mineral, which is believed to account for the elastic deformation. The validity of this model is shown in this study based on analysis of the bones of vitamin B6-deficient and vitamin B6-replete chick bones. In this model, when B6-deficient and control animals are compared, vitamin B6 deficiency has no effect on the mineral content or composition of cortical bone as measured by ash weight (63 +/- 6 vs. 58 +/- 3); mineral to matrix ratio of the FTIR spectra (4.2 +/- 0.6 vs. 4.5 +/- 0.2), line-broadening analyses of the X-ray diffraction 002 peak (beta 002 = 0.50 +/- 0.1 vs. 0.49 +/- 0.01), or other features of the infrared spectra. In contrast, collagen was significantly more extractable from vitamin B6-deficient chick bones (20 +/- 2% of total hydroxyproline extracted vs. 10 +/- 3% p < or = 0.001). The B6-deficient bones also contained an increased amount of the reducible cross-links DHLNL, dehydro-dihydroxylysinonorleucine, (1.03 +/- 0.07 vs. 0.84 +/- 0.13 p < or = 0.001); and a nonsignificant increase in HLNL, dehydro-hydroxylysinonorleucine, (0.51 +/- 0.03 vs. 0.43 +/- 0.03, p < or = 0.10). There were no significant changes in bone length, bone diameter, or area moment of inertia. In four-point bending, no significant changes in elastic modulus, stiffness, offset yield deflection, or fracture deflection were detected. However, fracture load in the B6-deficient animals was decreased from 203 +/- 35 MPa to 151 +/- 23 MPa, p < or = 0.01, and offset yield load was decreased from 165 +/- 9 MPa to 125 +/- 14 MPa, p < or = 0.05. Since earlier histomorphometric studies had demonstrated that the B6-deficient bones were osteopenic, these data suggest that although proper cortical bone mineralization occurred, the alterations of the collagen resulted in changes to bone mechanical performance.

  2. Exposure to serotonin adversely affects oligodendrocyte development and myelination in vitro.

    PubMed

    Fan, Lir-Wan; Bhatt, Abhay; Tien, Lu-Tai; Zheng, Baoying; Simpson, Kimberly L; Lin, Rick C S; Cai, Zhengwei; Kumar, Praveen; Pang, Yi

    2015-05-01

    patterns of contactin-associated protein (Caspr) clustering were observed at the sites of Node of Ranvier, suggesting that 5-HT exposure may affect other axon-derived factors for myelination. In summary, this is the first study to demonstrate that manipulation of serotonin levels affects OL development and myelination, which may contribute to altered neural connectivity noted in SSRIs-treated animals. The current in vitro study demonstrated that exposure to high level of serotonin (5-HT) led to aberrant oligodendrocyte (OL) development, cell injury, and myelination deficit. We propose that elevated extracellular serotonin levels in the fetal brain, such as upon the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy, may adversely affect OL development and/or myelination, thus contributing to altered neural connectivity seen in Autism Spectrum Disorders. OPC = oligodendrocyte progenitor cell. PMID:25382136

  3. Cochlear otosclerosis: does bone formation affect cochlear implant surgery?

    PubMed

    Fayad, J; Moloy, P; Linthicum, F H

    1990-05-01

    This study aimed to demonstrate that new bone formation in the scala tympani of patients deaf from otosclerosis does not preclude cochlear implant surgery. In seven temporal bones from patients with otosclerosis, we measured the extent of new bone from the round window to the distal part of the new growth. We compared results to surgical data on the extent of drilling and depth and ease of placement of the electrode in 20 patients deaf from otosclerosis. We also examined clinical performance and voltage requirements for long-term implant use in patients with and patients without ossification of the scala tympani. Findings in our limited sample of patients and bones show that obstruction of the basal turn, which occurs in some otosclerotic patients, does not preclude implant surgery. The dynamic range in the studied sample was relatively stable long-term and clinical performance did not differ between groups with and without an ossified scala tympani. PMID:2188511

  4. Correlation of adverse effects of cisplatin administration in patients affected by solid tumours: A retrospective evaluation

    PubMed Central

    ASTOLFI, LAURA; GHISELLI, SARA; GUARAN, VALERIA; CHICCA, MILVIA; SIMONI, EDI; OLIVETTO, ELENA; LELLI, GIORGIO; MARTINI, ALESSANDRO

    2013-01-01

    Cisplatin is the most common antineoplastic drug used for the therapy of solid tumours. To date, researchers have focused on the dosage to be administered for each specific tumour, mainly considering the local adverse effects. The aim of this study was to correlate the severity of the adverse effects with: i) the dosage of cisplatin; ii) the specific site of the tumour; iii) the association with other drugs; and iv) the symptoms. We analysed data from 123 patients with 11 different tumour classes undergoing therapy from 2007 to 2008 at St. Anna Hospital (Ferrara, Italy), using the Spearman non-parametric correlation index. Even though significant correlations were found among the variables, the overall results showed that the main factor influencing the severity of the adverse effects was the dosage of cisplatin administered. PMID:23404427

  5. Adverse Biological Effect of TiO2 and Hydroxyapatite Nanoparticles Used in Bone Repair and Replacement

    PubMed Central

    Wang, Jiangxue; Wang, Liting; Fan, Yubo

    2016-01-01

    The adverse biological effect of nanoparticles is an unavoidable scientific problem because of their small size and high surface activity. In this review, we focus on nano-hydroxyapatite and TiO2 nanoparticles (NPs) to clarify the potential systemic toxicological effect and cytotoxic response of wear nanoparticles because they are attractive materials for bone implants and are widely investigated to promote the repair and reconstruction of bone. The wear nanoparticles would be prone to binding with proteins to form protein-particle complexes, to interacting with visible components in the blood including erythrocytes, leukocytes, and platelets, and to being phagocytosed by macrophages or fibroblasts to deposit in the local tissue, leading to the formation of fibrous local pseudocapsules. These particles would also be translocated to and disseminated into the main organs such as the lung, liver and spleen via blood circulation. The inflammatory response, oxidative stress, and signaling pathway are elaborated to analyze the potential toxicological mechanism. Inhibition of the oxidative stress response and signaling transduction may be a new therapeutic strategy for wear debris–mediated osteolysis. Developing biomimetic materials with better biocompatibility is our goal for orthopedic implants. PMID:27231896

  6. Moderate-intensity rotating magnetic fields do not affect bone quality and bone remodeling in hindlimb suspended rats.

    PubMed

    Jing, Da; Cai, Jing; Wu, Yan; Shen, Guanghao; Zhai, Mingming; Tong, Shichao; Xu, Qiaoling; Xie, Kangning; Wu, Xiaoming; Tang, Chi; Xu, Xinmin; Liu, Juan; Guo, Wei; Jiang, Maogang; Luo, Erping

    2014-01-01

    Abundant evidence has substantiated the positive effects of pulsed electromagnetic fields (PEMF) and static magnetic fields (SMF) on inhibiting osteopenia and promoting fracture healing. However, the osteogenic potential of rotating magnetic fields (RMF), another common electromagnetic application modality, remains poorly characterized thus far, although numerous commercial RMF treatment devices have been available on the market. Herein the impacts of RMF on osteoporotic bone microarchitecture, bone strength and bone metabolism were systematically investigated in hindlimb-unloaded (HU) rats. Thirty two 3-month-old male Sprague-Dawley rats were randomly assigned to the Control (n = 10), HU (n = 10) and HU with RMF exposure (HU+RMF, n = 12) groups. Rats in the HU+RMF group were subjected to daily 2-hour exposure to moderate-intensity RMF (ranging from 0.60 T to 0.38 T) at 7 Hz for 4 weeks. HU caused significant decreases in body mass and soleus muscle mass of rats, which were not obviously altered by RMF. Three-point bending test showed that the mechanical properties of femurs in HU rats, including maximum load, stiffness, energy absorption and elastic modulus were not markedly affected by RMF. µCT analysis demonstrated that 4-week RMF did not significantly prevent HU-induced deterioration of femoral trabecular and cortical bone microarchitecture. Serum biochemical analysis showed that RMF did not significantly change HU-induced decrease in serum bone formation markers and increase in bone resorption markers. Bone histomorphometric analysis further confirmed that RMF showed no impacts on bone remodeling in HU rats, as evidenced by unchanged mineral apposition rate, bone formation rate, osteoblast numbers and osteoclast numbers in cancellous bone. Together, our findings reveal that RMF do not significantly affect bone microstructure, bone mechanical strength and bone remodeling in HU-induced disuse osteoporotic rats. Our study indicates potentially

  7. Moderate-Intensity Rotating Magnetic Fields Do Not Affect Bone Quality and Bone Remodeling in Hindlimb Suspended Rats

    PubMed Central

    Shen, Guanghao; Zhai, Mingming; Tong, Shichao; Xu, Qiaoling; Xie, Kangning; Wu, Xiaoming; Tang, Chi; Xu, Xinmin; Liu, Juan; Guo, Wei; Jiang, Maogang; Luo, Erping

    2014-01-01

    Abundant evidence has substantiated the positive effects of pulsed electromagnetic fields (PEMF) and static magnetic fields (SMF) on inhibiting osteopenia and promoting fracture healing. However, the osteogenic potential of rotating magnetic fields (RMF), another common electromagnetic application modality, remains poorly characterized thus far, although numerous commercial RMF treatment devices have been available on the market. Herein the impacts of RMF on osteoporotic bone microarchitecture, bone strength and bone metabolism were systematically investigated in hindlimb-unloaded (HU) rats. Thirty two 3-month-old male Sprague-Dawley rats were randomly assigned to the Control (n = 10), HU (n = 10) and HU with RMF exposure (HU+RMF, n = 12) groups. Rats in the HU+RMF group were subjected to daily 2-hour exposure to moderate-intensity RMF (ranging from 0.60 T to 0.38 T) at 7 Hz for 4 weeks. HU caused significant decreases in body mass and soleus muscle mass of rats, which were not obviously altered by RMF. Three-point bending test showed that the mechanical properties of femurs in HU rats, including maximum load, stiffness, energy absorption and elastic modulus were not markedly affected by RMF. µCT analysis demonstrated that 4-week RMF did not significantly prevent HU-induced deterioration of femoral trabecular and cortical bone microarchitecture. Serum biochemical analysis showed that RMF did not significantly change HU-induced decrease in serum bone formation markers and increase in bone resorption markers. Bone histomorphometric analysis further confirmed that RMF showed no impacts on bone remodeling in HU rats, as evidenced by unchanged mineral apposition rate, bone formation rate, osteoblast numbers and osteoclast numbers in cancellous bone. Together, our findings reveal that RMF do not significantly affect bone microstructure, bone mechanical strength and bone remodeling in HU-induced disuse osteoporotic rats. Our study indicates potentially

  8. Stem cell origin differently affects bone tissue engineering strategies

    PubMed Central

    Mattioli-Belmonte, Monica; Teti, Gabriella; Salvatore, Viviana; Focaroli, Stefano; Orciani, Monia; Dicarlo, Manuela; Fini, Milena; Orsini, Giovanna; Di Primio, Roberto; Falconi, Mirella

    2015-01-01

    Bone tissue engineering approaches are encouraging for the improvement of conventional bone grafting technique drawbacks. Thanks to their self-renewal and multi-lineage differentiation ability, stem cells are one of the major actors in tissue engineering approaches, and among these adult mesenchymal stem cells (MSCs) hold a great promise for regenerative medicine strategies. Bone marrow MSCs (BM-MSCs) are the first- identified and well-recognized stem cell population used in bone tissue engineering. Nevertheless, several factors hamper BM-MSC clinical application and subsequently, new stem cell sources have been investigated for these purposes. The fruitful selection and combination of tissue engineered scaffold, progenitor cells, and physiologic signaling molecules allowed the surgeon to reconstruct the missing natural tissue. On the basis of these considerations, we analyzed the capability of two different scaffolds, planned for osteochondral tissue regeneration, to modulate differentiation of adult stem cells of dissimilar local sources (i.e., periodontal ligament, maxillary periosteum) as well as adipose-derived stem cells (ASCs), in view of possible craniofacial tissue engineering strategies. We demonstrated that cells are differently committed toward the osteoblastic phenotype and therefore, taking into account their specific features, they could be intriguing cell sources in different stem cell-based bone/periodontal tissue regeneration approaches. PMID:26441682

  9. Cyclic cryopreservation affects the nanoscale material properties of trabecular bone.

    PubMed

    Landauer, Alexander K; Mondal, Sumona; Yuya, Philip A; Kuxhaus, Laurel

    2014-11-01

    Tissues such as bone are often stored via freezing, or cryopreservation. During an experimental protocol, bone may be frozen and thawed a number of times. For whole bone, the mechanical properties (strength and modulus) do not significantly change throughout five freeze-thaw cycles. Material properties at the trabecular and lamellar scales are distinct from whole bone properties, thus the impact of freeze-thaw cycling at this scale is unknown. To address this, the effect of repeated freezing on viscoelastic material properties of trabecular bone was quantified via dynamic nanoindentation. Vertebrae from five cervine spines (1.5-year-old, male) were semi-randomly assigned, three-to-a-cycle, to 0-10 freeze-thaw cycles. After freeze-thaw cycling, the vertebrae were dissected, prepared and tested. ANOVA (factors cycle, frequency, and donor) on storage modulus, loss modulus, and loss tangent, were conducted. Results revealed significant changes between cycles for all material properties for most cycles, no significant difference across most of the dynamic range, and significant differences between some donors. Regression analysis showed a moderate positive correlation between cycles and material property for loss modulus and loss tangent, and weak negative correlation for storage modulus, all correlations were significant. These results indicate that not only is elasticity unpredictably altered, but also that damping and viscoelasticity tend to increase with additional freeze-thaw cycling. PMID:25278046

  10. Severe Affective and Behavioural Dysregulation Is Associated with Significant Psychosocial Adversity and Impairment

    ERIC Educational Resources Information Center

    Jucksch, Viola; Salbach-Andrae, Harriet; Lenz, Klaus; Goth, Kirstin; Dopfner, Manfred; Poustka, Fritz; Freitag, Christine M.; Lehmkuhl, Gerd; Lehmkuhl, Ulrike; Holtmann, Martin

    2011-01-01

    Background: Recently, a highly heritable behavioral phenotype of simultaneous deviance on the Anxious/Depressed, Attention Problems, and Aggressive Behavior syndrome scales has been identified on the Child Behavior Checklist (CBCL-Dysregulation Profile, CBCL-DP). This study aims to investigate psychosocial adversity and impairment of the CBCL-DP.…

  11. Genetic selection to increase bone strength affects prevalence of keel bone damage and egg parameters in commercially housed laying hens.

    PubMed

    Stratmann, A; Fröhlich, E K F; Gebhardt-Henrich, S G; Harlander-Matauschek, A; Würbel, H; Toscano, M J

    2016-05-01

    The prevalence of keel bone damage as well as external egg parameters of 2 pure lines divergently selected for high (H) and low (L) bone strength were investigated in 2 aviary systems under commercial conditions. A standard LSL hybrid was used as a reference group. Birds were kept mixed per genetic line (77 hens of the H and L line and 201 or 206 hens of the LSL line, respectively, per pen) in 8 pens of 2 aviary systems differing in design. Keel bone status and body mass of 20 focal hens per line and pen were assessed at 17, 18, 23, 30, 36, 43, 52, and 63 wk of age. External egg parameters (i.e., egg mass, eggshell breaking strength, thickness, and mass) were measured using 10 eggs per line at both 38 and 57 wk of age. Body parameters (i.e. tarsus and third primary wing feather length to calculate index of wing loading) were recorded at 38 wk of age and mortality per genetic line throughout the laying cycle. Bone mineral density (BMD) of 15 keel bones per genetic line was measured after slaughter to confirm assignment of the experimental lines. We found a greater BMD in the H compared with the L and LSL lines. Fewer keel bone fractures and deviations, a poorer external egg quality, as well as a lower index of wing loading were found in the H compared with the L line. Mortality was lower and production parameters (e.g., laying performance) were higher in the LSL line compared with the 2 experimental lines. Aviary design affected prevalence of keel bone damage, body mass, and mortality. We conclude that selection of specific bone traits associated with bone strength as well as the related differences in body morphology (i.e., lower index of wing loading) have potential to reduce keel bone damage in commercial settings. Also, the housing environment (i.e., aviary design) may have additive effects. PMID:26944960

  12. Acute hypothalamic suppression significantly affects trabecular bone but not cortical bone following recovery and ovariectomy surgery in a rat model

    PubMed Central

    Mitchell, Kathryn A.; Lunny, Megan

    2016-01-01

    Background. Osteoporosis is “a pediatric disease with geriatric consequences.” Bone morphology and tissue quality co-adapt during ontogeny for sufficient bone stiffness. Altered bone morphology from hypothalamic amenorrhea, a risk factor for low bone mass in women, may affect bone strength later in life. Our purpose was to determine if altered morphology following hypothalamic suppression during development affects cortical bone strength and trabecular bone volume (BV/TV) at maturity. Methods. Female rats (25 days old) were assigned to a control (C) group (n = 45) that received saline injections (.2 cc) or an experimental group (GnRH-a) (n = 45) that received gonadotropin releasing hormone antagonist injections (.24 mg per dose) for 25 days. Fifteen animals from each group were sacrificed immediately after the injection protocol at Day 50 (C, GnRH-a). The remaining animals recovered for 135 days and a subset of each group was sacrificed at Day 185 ((C-R) (n = 15) and (G-R) (n = 15)). The remaining animals had an ovariectomy surgery (OVX) at 185 days of age and were sacrificed 40 days later (C-OVX) (n = 15) and (G-OVX) (n = 15). After sacrifice femurs were mechanically tested and scanned using micro CT. Serum C-terminal telopeptides (CTX) and insulin-like growth factor 1 (IGF-1) were measured. Two-way ANOVA (2 groups (GnRH-a and Control) X 3 time points (Injection Protocol, Recovery, post-OVX)) was computed. Results. GnRH-a injections suppressed uterine weights (72%) and increased CTX levels by 59%. Bone stiffness was greater in the GnRH-a groups compared to C. Ash content and cortical bone area were similar between groups at all time points. Polar moment of inertia, a measure of bone architecture, was 15% larger in the GnRH-a group and remained larger than C (19%) following recovery. Both the polar moment of inertia and cortical area increased linearly with the increases in body weight. Following the injection protocol, trabecular BV/TV was 31% lower in the Gn

  13. Acute hypothalamic suppression significantly affects trabecular bone but not cortical bone following recovery and ovariectomy surgery in a rat model.

    PubMed

    Yingling, Vanessa R; Mitchell, Kathryn A; Lunny, Megan

    2016-01-01

    Background. Osteoporosis is "a pediatric disease with geriatric consequences." Bone morphology and tissue quality co-adapt during ontogeny for sufficient bone stiffness. Altered bone morphology from hypothalamic amenorrhea, a risk factor for low bone mass in women, may affect bone strength later in life. Our purpose was to determine if altered morphology following hypothalamic suppression during development affects cortical bone strength and trabecular bone volume (BV/TV) at maturity. Methods. Female rats (25 days old) were assigned to a control (C) group (n = 45) that received saline injections (.2 cc) or an experimental group (GnRH-a) (n = 45) that received gonadotropin releasing hormone antagonist injections (.24 mg per dose) for 25 days. Fifteen animals from each group were sacrificed immediately after the injection protocol at Day 50 (C, GnRH-a). The remaining animals recovered for 135 days and a subset of each group was sacrificed at Day 185 ((C-R) (n = 15) and (G-R) (n = 15)). The remaining animals had an ovariectomy surgery (OVX) at 185 days of age and were sacrificed 40 days later (C-OVX) (n = 15) and (G-OVX) (n = 15). After sacrifice femurs were mechanically tested and scanned using micro CT. Serum C-terminal telopeptides (CTX) and insulin-like growth factor 1 (IGF-1) were measured. Two-way ANOVA (2 groups (GnRH-a and Control) X 3 time points (Injection Protocol, Recovery, post-OVX)) was computed. Results. GnRH-a injections suppressed uterine weights (72%) and increased CTX levels by 59%. Bone stiffness was greater in the GnRH-a groups compared to C. Ash content and cortical bone area were similar between groups at all time points. Polar moment of inertia, a measure of bone architecture, was 15% larger in the GnRH-a group and remained larger than C (19%) following recovery. Both the polar moment of inertia and cortical area increased linearly with the increases in body weight. Following the injection protocol, trabecular BV/TV was 31% lower in the Gn

  14. Pinto Bean Hull Extract Supplementation Favorably Affects Markers of Bone Metabolism and Bone Structure in Mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bean hulls are rich in phenolic compounds known to possess antioxidant activity that may have beneficial effect on bone health. The aim of this study was to examine the effects of bean hull extract (BHE) from pinto beans on bone structure and serum markers in twelve-month-old male C57BL/6 mice fed e...

  15. Does aspiration of bones and joints affect results of later bone scanning

    SciTech Connect

    Canale, S.T.; Harkness, R.M.; Thomas, P.A.; Massie, J.D.

    1985-01-01

    To determine the effect, if any, of needle aspiration on /sup 99m/Tc bone scanning, three different areas of 15 dogs were first aspirated and then imaged with technetium bone scintigraphy. The hip joint was aspirated, the distal femoral metaphysis was drilled and aspirated, and the tibial periosteum was scraped with an 18- or 20-gauge needle. Varying amounts of trauma were inflicted to simulate varying difficulties at aspiration. /sup 99m/Tc bone scans were obtained from 5 h to 10 days later. There was no evidence of focal technetium uptake after any hip joint aspiration. This was consistent regardless of the amount of trauma inflicted or the time from aspiration to bone scanning. Metaphyseal cortical drilling and tibial periosteal scraping occasionally caused some focal uptake when scanning was delayed greater than 2 days. When osteomyelitis or pyarthrosis is clinically suspected, joint aspiration can be performed without fear of producing a false- positive bone scan.

  16. Adverse Prognostic Impact of Bone Marrow Microvessel Density in Multiple Myeloma

    PubMed Central

    Lee, Nuri; Lee, Hyewon; Moon, Soo Young; Sohn, Ji Yeon; Hwang, Sang Mee; Yoon, Ok Jin; Youn, Hye Sun

    2015-01-01

    Background Angiogenesis is important for the proliferation and survival of multiple myeloma (MM) cells. Bone marrow (BM) microvessel density (MVD) is a useful marker of angiogenesis and is determined by immunohistochemical staining with anti-CD34 antibody. This study investigated the prognostic impact of MVD and demonstrated the relationship between MVD and previously mentioned prognostic factors in patients with MM. Methods The study included 107 patients with MM. MVD was assessed at initial diagnosis in a blinded manner by two hematopathologists who examined three CD34-positive hot spots per patient and counted the number of vessels in BM samples. Patients were divided into three groups according to MVD tertiles. Cumulative progression-free survival (PFS) and overall survival (OS) curves, calculated by using Kaplan-Meier method, were compared among the three groups. Prognostic impact of MVD was assessed by calculating Cox proportional hazard ratio (HR). Results Median MVDs in the three groups were 16.8, 33.9, and 54.7. MVDs were correlated with other prognostic factors, including β2-microglobulin concentration, plasma cell percentage in the BM, and cancer stage according to the International Staging System. Multivariate Cox regression analysis showed that high MVD was an independent predictor of PFS (HR=2.57; 95% confidence interval, 1.22-5.42; P=0.013). PFS was significantly lower in the high MVD group than in the low MVD group (P=0.025). However, no difference was observed in the OS (P=0.428). Conclusions Increased BM MVD is a marker of poor prognosis in patients newly diagnosed with MM. BM MVD should be assessed at the initial diagnosis of MM. PMID:26354343

  17. Rat rotator cuff tendon-to-bone healing properties are adversely affected by hypercholesterolemia

    PubMed Central

    Beason, David P.; Tucker, Jennica J.; Lee, Chang Soo; Edelstein, Lena; Abboud, Joseph A.; Soslowsky, Louis J.

    2014-01-01

    Background Rotator cuff tendon tears represent a major component of reported orthopaedic injuries. In addition, more than one quarter of U.S. adults either currently have high cholesterol levels or have reduced their previously high cholesterol levels through the use of pharmaceuticals. Our clinical data have already linked hypercholesterolemia to full-thickness rotator cuff tears, and experimental data from our laboratory have shown effects on native tendon properties in multiple species. The objective of this study was to evaluate healing of supraspinatus tendons in our rat rotator cuff injury model. We hypothesized that tendon healing would be inferior in rats receiving a high-cholesterol diet for 6 months compared with those receiving standard chow. Methods All animals were subjected to a unilateral supraspinatus detachment and repair surgery, with contralateral limbs serving as within-animal comparative data. Animals continued their respective diet courses, and their supraspinatus tendons were biomechanically or histologically evaluated at 2, 4, and 8 weeks postoperatively. Results Biomechanical testing revealed a significant reduction in normalized stiffness in hypercholesterolemic rats compared with controls at 4 weeks after injury, whereas histologic analyses showed no significant differences in collagen organization, cellularity, or cell shape between groups. Conclusion On the basis of our findings, hypercholesterolemia may have a detrimental biomechanical effect on tendon healing in our rat rotator cuff injury and repair model. Level of evidence Basic Science Study, Animal Model. PMID:24295837

  18. Modifications of histamine receptor signaling affect bone mechanical properties in rats.

    PubMed

    Folwarczna, Joanna; Janas, Aleksandra; Pytlik, Maria; Śliwiński, Leszek; Wiercigroch, Marek; Brzęczek, Anna

    2014-02-01

    Histamine receptors are expressed on bone cells and histamine may be involved in regulation of bone metabolism. The aim of the present study was to investigate the effects of loratadine (an H(1) receptor antagonist), ranitidine (an H(2) receptor antagonist) and betahistine (an H(3) receptor antagonist and H(1) receptor agonist) on bone mechanical properties in rats. Loratadine (5 mg/kg/day, po), ranitidine (50 mg/kg/day, po), or betahistine dihydrochloride (5 mg/kg/day, po), were administered for 4 weeks to non-ovariectomized and bilaterally ovariectomized (estrogen-deficient) 3-month-old rats, and their effects were compared with appropriate controls. Serum levels of bone turnover markers, bone mineralization and mechanical properties of the proximal tibial metaphysis, femoral diaphysis and femoral neck were studied. In rats with normal estrogen level, administration of loratadine slightly favorably affected mechanical properties of compact bone, significantly increasing the strength of the femoral neck (p < 0.05), and tending to increase the strength of the femoral diaphysis. Ranitidine did not significantly affect the investigated parameters, and betahistine decreased the strength of the tibial metaphysis (cancellous bone, p < 0.01). There were no significant effects of the drugs on serum bone turnover markers. In estrogen-deficient rats, the drugs did not significantly affect the investigated skeletal parameters. In conclusion, the effects of histamine H(1), H(2) and H(3) receptor antagonists on the skeletal system in rats were differential and dependent on estrogen status. PMID:24905313

  19. 30 CFR 285.816 - What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility? 285.816 Section 285.816 Mineral Resources..., pipeline, or facility? If environmental or other conditions adversely affect a cable, pipeline, or...

  20. Does Maternal Prenatal Stress Adversely Affect the Child's Learning and Memory at Age Six?

    ERIC Educational Resources Information Center

    Gutteling, Barbara M.; de Weerth, Carolina; Zandbelt, Noortje; Mulder, Eduard J. H.; Visser, Gerard H. A.; Buitelaar, Jan K.

    2006-01-01

    Prenatal maternal stress has been shown to affect postnatal development in animals and humans. In animals, the morphology and function of the offspring's hippocampus is negatively affected by prenatal maternal stress. The present study prospectively investigated the influence of prenatal maternal stress on learning and memory of 112 children (50…

  1. A systematic review of psychosocial factors affecting survival after bone marrow transplantation.

    PubMed

    Hoodin, Flora; Weber, Shauncie

    2003-01-01

    An electronic database search identified 15 studies of psychosocial factors affecting survival after bone marrow transplantation. The studies were assessed for methodological quality by two reviewers using the procedures of Bland and colleagues. Although some studies found that psychological variables affect survival after bone marrow transplantation, the reviewers' analysis of the methodologically sound studies suggested that survival after bone marrow transplantation is not substantively affected by depressed mood or other psychopathology in adults or by social support in adults or children. Longer survival may be related to lower "anxious preoccupation," higher "fighting spirit," and better quality of life ratings before and soon after transplant in adults. Overall, however, the literature is insufficiently developed to provide definitive evidence for a relationship between psychological variables and survival after bone marrow transplantation. Future primary studies in this area should be designed to maximize replicability and generalizability. PMID:12724499

  2. Can aircraft noise less than or equal 115 to dBA adversely affect reproductive outcome in USAF women?

    NASA Astrophysics Data System (ADS)

    Brubaker, P. A.

    1985-06-01

    It has been suggested, mainly through animal studies, that exposure to high noise levels may be associated with lower birth weight, reduced gestational length and other adverse reproductive outcomes. Few studies have been done on humans to show this association. The Air Force employs pregnant women in areas where there is a high potential for exposure to high noise levels. This study proposes a method to determine if there is an association between high frequency noise levels or = 115 dBA and adverse reproductive outcomes through a review of records and self-administered questionnaires in a case-comparison design. Prevelance rates will be calculated and a multiple logistic regression analysis computed for the independent variables that can affect reproduction.

  3. Adverse childhood experiences associate to reduced glutamate levels in the hippocampus of patients affected by mood disorders.

    PubMed

    Poletti, Sara; Locatelli, Clara; Falini, Andrea; Colombo, Cristina; Benedetti, Francesco

    2016-11-01

    Adverse childhood experiences (ACE) can possibly permanently alter the stress response system, affect the glutamatergic system and influence hippocampal volume in mood disorders. The aim of the study is to investigate the association between glutamate levels in the hippocampus, measured through single proton magnetic resonance spectroscopy (1H-MRS), and ACE in patients affected by mood disorders and healthy controls. Higher levels of early stress associate to reduced levels of Glx/Cr in the hippocampus in depressed patients but not in healthy controls. Exposure to stress during early life could lead to a hypofunctionality of the glutamatergic system in the hippocampus of depressed patients. Abnormalities of glutamatergic signaling could then possibly underpin the structural and functional abnormalities observed in patients affected by mood disorders. PMID:27449360

  4. A Traditional Chinese Medicine Xiao-Ai-Tong Suppresses Pain through Modulation of Cytokines and Prevents Adverse Reactions of Morphine Treatment in Bone Cancer Pain Patients

    PubMed Central

    Cong, Yan; Sun, Kefu; He, Xueming; Li, Jinxuan; Dong, Yanbin; Zheng, Bin; Tan, Xiao; Song, Xue-Jun

    2015-01-01

    Treating cancer pain continues to possess a major challenge. Here, we report that a traditional Chinese medicine Xiao-Ai-Tong (XAT) can effectively suppress pain and adverse reactions following morphine treatment in patients with bone cancer pain. Visual Analogue Scale (VAS) and Quality of Life Questionnaire (EORTC QLQ-C30) were used for patient's self-evaluation of pain intensity and evaluating changes of adverse reactions including constipation, nausea, fatigue, and anorexia, respectively, before and after treatment prescriptions. The clinical trials showed that repetitive oral administration of XAT (200 mL, bid, for 7 consecutive days) alone greatly reduced cancer pain. Repetitive treatment with a combination of XAT and morphine (20 mg and 30 mg, resp.) produced significant synergistic analgesic effects. Meanwhile, XAT greatly reduced the adverse reactions associated with cancer and/or morphine treatment. In addition, XAT treatment significantly reduced the proinflammatory cytokines interleukin-1β and tumor necrosis factor-α and increased the endogenous anti-inflammatory cytokine interleukin-10 in blood. These findings demonstrate that XAT can effectively reduce bone cancer pain probably mediated by the cytokine mechanisms, facilitate analgesic effect of morphine, and prevent or reduce the associated adverse reactions, supporting a use of XAT, alone or with morphine, in treating bone cancer pain in clinic. PMID:26617438

  5. Elevated depressive affect is associated with adverse cardiovascular outcomes among African Americans with chronic kidney disease

    PubMed Central

    Fischer, Michael J.; Kimmel, Paul L.; Greene, Tom; Gassman, Jennifer J.; Wang, Xuelei; Brooks, Deborah H.; Charleston, Jeanne; Dowie, Donna; Thornley-Brown, Denyse; Cooper, Lisa A.; Bruce, Marino A.; Kusek, John W.; Norris, Keith C.; Lash, James P.

    2011-01-01

    This study was designed to examine the impact of elevated depressive affect on health outcomes among participants with hypertensive chronic kidney disease in the African-American Study of Kidney Disease and Hypertension (AASK) Cohort Study. Elevated depressive affect was defined by Beck Depression Inventory II (BDI-II) thresholds of 11 or more, above 14, and by 5-Unit increments in the score. Cox regression analyses were used to relate cardiovascular death/hospitalization, doubling of serum creatinine/end-stage renal disease, overall hospitalization, and all-cause death to depressive affect evaluated at baseline, the most recent annual visit (time-varying), or average from baseline to the most recent visit (cumulative). Among 628 participants at baseline, 42% had BDI-II scores of 11 or more and 26% had a score above 14. During a 5-year follow-up, the cumulative incidence of cardiovascular death/hospitalization was significantly greater for participants with baseline BDI-II scores of 11 or more compared with those with scores <11. The baseline, time-varying, and cumulative elevated depressive affect were each associated with a significant higher risk of cardiovascular death/hospitalization, especially with a time-varying BDI-II score over 14 (adjusted HR 1.63) but not with the other outcomes. Thus, elevated depressive affect is associated with unfavorable cardiovascular outcomes in African Americans with hypertensive chronic kidney disease. PMID:21633409

  6. Water pollution by Cu and Pb can adversely affect mallard embryonic development.

    PubMed

    Kertész, Virág; Bakonyi, Gábor; Farkas, Beáta

    2006-09-01

    The effects of heavy metal pollutants on aquatic birds have been widely studied in ecotoxicological investigations; however, the predominant focus has been on the postnatal period of life. Limited information on the adverse effects of metals to bird eggs is available. The possible toxic effects of lead and copper were studied in mallard eggs. After the accidental severe heavy metal pollution of the Tisa river (Hungary) in March 2000, these metals were detected in the highest concentration in both the water and the sediment, reaching far beyond acceptable concentrations. Pb treatment (2.9 mg/L) significantly increased the rate of mortality after a single immersion of the eggs into polluted water for 30 min. The rate of dead embryos significantly increased after the combined exposure to Cu and Pb (0.86 and 2.9 mg/L, respectively) both in the single- (once for 30 min) and in the multiple- (10s daily during first trimester of incubation) immersion groups. It was concluded that elevated metal concentrations similar to those found in the Tisa river after the tailing dam failure may cause toxic effects (mortality and teratogenicity) upon exposure of mallard eggs. PMID:16678261

  7. Orphan nuclear receptor Nur77 affects cardiomyocyte calcium homeostasis and adverse cardiac remodelling

    PubMed Central

    Medzikovic, Lejla; Schumacher, Cees A.; Verkerk, Arie O.; van Deel, Elza D.; Wolswinkel, Rianne; van der Made, Ingeborg; Bleeker, Natascha; Cakici, Daniella; van den Hoogenhof, Maarten M. G.; Meggouh, Farid; Creemers, Esther E.; Ann Remme, Carol; Baartscheer, Antonius; de Winter, Robbert J.; de Vries, Carlie J. M.; Arkenbout, E. Karin; de Waard, Vivian

    2015-01-01

    Distinct stressors may induce heart failure. As compensation, β-adrenergic stimulation enhances myocardial contractility by elevating cardiomyocyte intracellular Ca2+ ([Ca2+]i). However, chronic β-adrenergic stimulation promotes adverse cardiac remodelling. Cardiac expression of nuclear receptor Nur77 is enhanced by β-adrenergic stimulation, but its role in cardiac remodelling is still unclear. We show high and rapid Nur77 upregulation in cardiomyocytes stimulated with β-adrenergic agonist isoproterenol. Nur77 knockdown in culture resulted in hypertrophic cardiomyocytes. Ventricular cardiomyocytes from Nur77-deficient (Nur77-KO) mice exhibited elevated diastolic and systolic [Ca2+]i and prolonged action potentials compared to wild type (WT). In vivo, these differences resulted in larger cardiomyocytes, increased expression of hypertrophic genes, and more cardiac fibrosis in Nur77-KO mice upon chronic isoproterenol stimulation. In line with the observed elevated [Ca2+]i, Ca2+-activated phosphatase calcineurin was more active in Nur77-KO mice compared to WT. In contrast, after cardiac pressure overload by aortic constriction, Nur77-KO mice exhibited attenuated remodelling compared to WT. Concluding, Nur77-deficiency results in significantly altered cardiac Ca2+ homeostasis and distinct remodelling outcome depending on the type of insult. Detailed knowledge on the role of Nur77 in maintaining cardiomyocyte Ca2+ homeostasis and the dual role Nur77 plays in cardiac remodelling will aid in developing personalized therapies against heart failure. PMID:26486271

  8. Coralline algal physiology is more adversely affected by elevated temperature than reduced pH.

    PubMed

    Vásquez-Elizondo, Román Manuel; Enríquez, Susana

    2016-01-01

    In this study we analyzed the physiological responses of coralline algae to ocean acidification (OA) and global warming, by exposing algal thalli of three species with contrasting photobiology and growth-form to reduced pH and elevated temperature. The analysis aimed to discern between direct and combined effects, while elucidating the role of light and photosynthesis inhibition in this response. We demonstrate the high sensitivity of coralline algae to photodamage under elevated temperature and its severe consequences on thallus photosynthesis and calcification rates. Moderate levels of light-stress, however, were maintained under reduced pH, resulting in no impact on algal photosynthesis, although moderate adverse effects on calcification rates were still observed. Accordingly, our results support the conclusion that global warming is a stronger threat to algal performance than OA, in particular in highly illuminated habitats such as coral reefs. We provide in this study a quantitative physiological model for the estimation of the impact of thermal-stress on coralline carbonate production, useful to foresee the impact of global warming on coralline contribution to reef carbon budgets, reef cementation, coral recruitment and the maintenance of reef biodiversity. This model, however, cannot yet account for the moderate physiological impact of low pH on coralline calcification. PMID:26740396

  9. Coralline algal physiology is more adversely affected by elevated temperature than reduced pH

    PubMed Central

    Vásquez-Elizondo, Román Manuel; Enríquez, Susana

    2016-01-01

    In this study we analyzed the physiological responses of coralline algae to ocean acidification (OA) and global warming, by exposing algal thalli of three species with contrasting photobiology and growth-form to reduced pH and elevated temperature. The analysis aimed to discern between direct and combined effects, while elucidating the role of light and photosynthesis inhibition in this response. We demonstrate the high sensitivity of coralline algae to photodamage under elevated temperature and its severe consequences on thallus photosynthesis and calcification rates. Moderate levels of light-stress, however, were maintained under reduced pH, resulting in no impact on algal photosynthesis, although moderate adverse effects on calcification rates were still observed. Accordingly, our results support the conclusion that global warming is a stronger threat to algal performance than OA, in particular in highly illuminated habitats such as coral reefs. We provide in this study a quantitative physiological model for the estimation of the impact of thermal-stress on coralline carbonate production, useful to foresee the impact of global warming on coralline contribution to reef carbon budgets, reef cementation, coral recruitment and the maintenance of reef biodiversity. This model, however, cannot yet account for the moderate physiological impact of low pH on coralline calcification. PMID:26740396

  10. Weight Reduction in Athletes May Adversely Affect the Phagocytic Function of Monocytes.

    ERIC Educational Resources Information Center

    Kono, Ichiro; And Others

    1988-01-01

    Study of the monocyte phagocytic function in nine competitive athletes before and after a two-week weight reduction (through calorie restriction) program revealed that their pre-program phagocytic activity was higher than in sedentary controls but decreased significantly after the program. This suggests calorie restriction may affect the human…

  11. Cell and Signal Components of the Microenvironment of Bone Metastasis Are Affected by Hypoxia

    PubMed Central

    Bendinelli, Paola; Maroni, Paola; Matteucci, Emanuela; Desiderio, Maria Alfonsina

    2016-01-01

    Bone metastatic cells release bone microenvironment proteins, such as the matricellular protein SPARC (secreted protein acidic and rich in cysteine), and share a cell signaling typical of the bone metabolism controlled by Runx2. The megakaryocytes in the bone marrow engrafted by the metastases seem to be one of the principal microenvironment sources of the biological stimuli, implicated in the formation of an osteoblastic niche, and affecting metastasis phenotype and colonization. Educated platelets in the circulation might derive from megakaryocytes in bone metastasis. The evaluation of predictive markers in the circulating platelets might be useful for the stratification of patients for therapeutic purposes. The hypoxic environment in bone metastasis is one of the key regulators of the network of the biological soluble and structural components of the matrix. In bone metastatic cells under hypoxia, similar patterns of Runx2 and SPARC are observed, both showing downregulation. Conversely, hypoxia induces Endothelin 1, which upregulates SPARC, and these biological stimuli may be considered prognostic markers of bone metastasis in breast carcinoma patients. PMID:27187355

  12. Cell and Signal Components of the Microenvironment of Bone Metastasis Are Affected by Hypoxia.

    PubMed

    Bendinelli, Paola; Maroni, Paola; Matteucci, Emanuela; Desiderio, Maria Alfonsina

    2016-01-01

    Bone metastatic cells release bone microenvironment proteins, such as the matricellular protein SPARC (secreted protein acidic and rich in cysteine), and share a cell signaling typical of the bone metabolism controlled by Runx2. The megakaryocytes in the bone marrow engrafted by the metastases seem to be one of the principal microenvironment sources of the biological stimuli, implicated in the formation of an osteoblastic niche, and affecting metastasis phenotype and colonization. Educated platelets in the circulation might derive from megakaryocytes in bone metastasis. The evaluation of predictive markers in the circulating platelets might be useful for the stratification of patients for therapeutic purposes. The hypoxic environment in bone metastasis is one of the key regulators of the network of the biological soluble and structural components of the matrix. In bone metastatic cells under hypoxia, similar patterns of Runx2 and SPARC are observed, both showing downregulation. Conversely, hypoxia induces Endothelin 1, which upregulates SPARC, and these biological stimuli may be considered prognostic markers of bone metastasis in breast carcinoma patients. PMID:27187355

  13. 30 CFR 585.816 - What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 2 2014-07-01 2014-07-01 false What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility? 585.816 Section 585.816 Mineral Resources BUREAU... corrective action to BOEM within 30 days of the discovery of the adverse effect. (b) Take remedial action...

  14. 30 CFR 285.816 - What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 2 2011-07-01 2011-07-01 false What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility? 285.816 Section 285.816 Mineral Resources BUREAU...: (a) Submit a plan of corrective action to MMS within 30 days of the discovery of the adverse...

  15. 30 CFR 585.816 - What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 2 2012-07-01 2012-07-01 false What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility? 585.816 Section 585.816 Mineral Resources BUREAU... corrective action to BOEM within 30 days of the discovery of the adverse effect. (b) Take remedial action...

  16. 30 CFR 585.816 - What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 2 2013-07-01 2013-07-01 false What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility? 585.816 Section 585.816 Mineral Resources BUREAU... corrective action to BOEM within 30 days of the discovery of the adverse effect. (b) Take remedial action...

  17. The bone resorption inhibitors odanacatib and alendronate affect post-osteoclastic events differently in ovariectomized rabbits.

    PubMed

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Pennypacker, Brenda L; Duong, Le T; Delaissé, Jean-Marie

    2014-02-01

    Odanacatib (ODN) is a bone resorption inhibitor which differs from standard antiresorptives by its ability to reduce bone resorption without decreasing bone formation. What is the reason for this difference? In contrast with other antiresorptives, such as alendronate (ALN), ODN targets only the very last step of the resorption process. We hypothesize that ODN may therefore modify the remodeling events immediately following osteoclastic resorption. These events belong to the reversal phase and include recruitment of osteoblasts, which is critical for connecting bone resorption to formation. We performed a histomorphometric study of trabecular remodeling in vertebrae of estrogen-deficient rabbits treated or not with ODN or ALN, a model where ODN, but not ALN, was previously shown to preserve bone formation. In line with our hypothesis, we found that ODN treatment compared to ALN results in a shorter reversal phase, faster initiation of osteoid deposition on the eroded surfaces, and higher osteoblast recruitment. The latter is reflected by higher densities of mature bone forming osteoblasts and an increased subpopulation of cuboidal osteoblasts. Furthermore, we found an increase in the interface between osteoclasts and surrounding osteoblast-lineage cells. This increase is expected to favor the osteoclast-osteoblast interactions required for bone formation. Regarding bone resorption itself, we show that ODN, but not ALN, treatment results in shallower resorption lacunae, a geometry favoring bone stiffness. We conclude that, compared to standard antiresorptives, ODN shows distinctive effects on resorption geometry and on reversal phase activities which positively affect osteoblast recruitment and may therefore favor bone formation. PMID:24085265

  18. Prebiotics, probiotics, and synbiotics affect mineral absorption, bone mineral content, and bone structure.

    PubMed

    Scholz-Ahrens, Katharina E; Ade, Peter; Marten, Berit; Weber, Petra; Timm, Wolfram; Açil, Yahya; Glüer, Claus-C; Schrezenmeir, Jürgen

    2007-03-01

    Several studies in animals and humans have shown positive effects of nondigestible oligosaccharides (NDO) on mineral absorption and metabolism and bone composition and architecture. These include inulin, oligofructose, fructooligosaccharides, galactooligosaccharides, soybean oligosaccharide, and also resistant starches, sugar alcohols, and difructose anhydride. A positive outcome of dietary prebiotics is promoted by a high dietary calcium content up to a threshold level and an optimum amount and composition of supplemented prebiotics. There might be an optimum composition of fructooligosaccharides with different chain lengths (synergy products). The efficacy of dietary prebiotics depends on chronological age, physiological age, menopausal status, and calcium absorption capacity. There is evidence for an independent probiotic effect on facilitating mineral absorption. Synbiotics, i.e., a combination of probiotics and prebiotics, can induce additional effects. Whether a low content of habitual NDO would augment the effect of dietary prebiotics or synbiotics remains to be studied. The underlying mechanisms are manifold: increased solubility of minerals because of increased bacterial production of short-chain fatty acids, which is promoted by the greater supply of substrate; an enlargement of the absorption surface by promoting proliferation of enterocytes mediated by bacterial fermentation products, predominantly lactate and butyrate; increased expression of calcium-binding proteins; improvement of gut health; degradation of mineral complexing phytic acid; release of bone-modulating factors such as phytoestrogens from foods; stabilization of the intestinal flora and ecology, also in the presence of antibiotics; stabilization of the intestinal mucus; and impact of modulating growth factors such as polyamines. In conclusion, prebiotics are the most promising but also best investigated substances with respect to a bone-health-promoting potential, compared with probiotics

  19. Depressing Antidepressant: Fluoxetine Affects Serotonin Neurons Causing Adverse Reproductive Responses in Daphnia magna.

    PubMed

    Campos, Bruno; Rivetti, Claudia; Kress, Timm; Barata, Carlos; Dircksen, Heinrich

    2016-06-01

    Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants. As endocrine disruptive contaminants in the environment, SSRIs affect reproduction in aquatic organisms. In the water flea Daphnia magna, SSRIs increase offspring production in a food ration-dependent manner. At limiting food conditions, females exposed to SSRIs produce more but smaller offspring, which is a maladaptive life-history strategy. We asked whether increased serotonin levels in newly identified serotonin-neurons in the Daphnia brain mediate these effects. We provide strong evidence that exogenous SSRI fluoxetine selectively increases serotonin-immunoreactivity in identified brain neurons under limiting food conditions thereby leading to maladaptive offspring production. Fluoxetine increases serotonin-immunoreactivity at low food conditions to similar maximal levels as observed under high food conditions and concomitantly enhances offspring production. Sublethal amounts of the neurotoxin 5,7-dihydroxytryptamine known to specifically ablate serotonin-neurons markedly decrease serotonin-immunoreactivity and offspring production, strongly supporting the effect to be serotonin-specific by reversing the reproductive phenotype attained under fluoxetine. Thus, SSRIs impair serotonin-regulation of reproductive investment in a planktonic key organism causing inappropriately increased reproduction with potentially severe ecological impact. PMID:27128505

  20. Combining S-cone and luminance signals adversely affects discrimination of objects within backgrounds

    PubMed Central

    Jennings, Ben J.; Tsattalios, Konstantinos; Chakravarthi, Ramakrishna; Martinovic, Jasna

    2016-01-01

    The visual system processes objects embedded in complex scenes that vary in both luminance and colour. In such scenes, colour contributes to the segmentation of objects from backgrounds, but does it also affect perceptual organisation of object contours which are already defined by luminance signals, or are these processes unaffected by colour’s presence? We investigated if luminance and chromatic signals comparably sustain processing of objects embedded in backgrounds, by varying contrast along the luminance dimension and along the two cone-opponent colour directions. In the first experiment thresholds for object/non-object discrimination of Gaborised shapes were obtained in the presence and absence of background clutter. Contrast of the component Gabors was modulated along single colour/luminance dimensions or co-modulated along multiple dimensions simultaneously. Background clutter elevated discrimination thresholds only for combined S-(L + M) and L + M signals. The second experiment replicated and extended this finding by demonstrating that the effect was dependent on the presence of relatively high S-(L + M) contrast. These results indicate that S-(L + M) signals impair spatial vision when combined with luminance. Since S-(L + M) signals are characterised by relatively large receptive fields, this is likely to be due to an increase in the size of the integration field over which contour-defining information is summed. PMID:26856308

  1. Nutrient supplementation may adversely affect maternal oral health--a randomised controlled trial in rural Malawi.

    PubMed

    Harjunmaa, Ulla; Järnstedt, Jorma; Dewey, Kathryn G; Ashorn, Ulla; Maleta, Kenneth; Vosti, Stephen A; Ashorn, Per

    2016-01-01

    Nutritional supplementation during pregnancy is increasingly recommended especially in low-resource settings, but its oral health impacts have not been studied. Our aim was to examine whether supplementation with multiple micronutrients (MMN) or small-quantity lipid-based nutrient supplements affects dental caries development or periodontal health in a rural Malawian population. The study was embedded in a controlled iLiNS-DYAD trial that enrolled 1391 pregnant women <20 gestation weeks. Women were provided with one daily iron-folic acid capsule (IFA), one capsule with 18 micronutrients (MMN) or one sachet of lipid-based nutrient supplements (LNS) containing protein, carbohydrates, essential fatty acids and 21 micronutrients. Oral examination of 1024 participants was conducted and panoramic X-ray taken within 6 weeks after delivery. The supplement groups were similar at baseline in average socio-economic, nutritional and health status. At the end of the intervention, the prevalence of caries was 56.7%, 69.1% and 63.3% (P = 0.004), and periodontitis 34.9%, 29.8% and 31.2% (P = 0.338) in the IFA, MMN and LNS groups, respectively. Compared with the IFA group, women in the MMN group had 0.60 (0.18-1.02) and in the LNS group 0.59 (0.17-1.01) higher mean number of caries lesions. In the absence of baseline oral health data, firm conclusions on causality cannot be drawn. However, although not confirmatory, the findings are consistent with a possibility that provision of MMN or LNS may have increased the caries incidence in this target population. Because of the potential public health impacts, further research on the association between gestational nutrient interventions and oral health in low-income settings is needed. PMID:26194850

  2. Obesity/hyperleptinemic phenotype adversely affects hippocampal plasticity: effects of dietary restriction.

    PubMed

    Grillo, Claudia A; Piroli, Gerardo G; Evans, Ashlie N; Macht, Victoria A; Wilson, Steven P; Scott, Karen A; Sakai, Randall R; Mott, David D; Reagan, Lawrence P

    2011-08-01

    Epidemiological studies estimate that greater than 60% of the adult US population may be categorized as either overweight or obese and there is a growing appreciation that obesity affects the functional integrity of the central nervous system (CNS). We recently developed a lentivirus (LV) vector that produces an insulin receptor (IR) antisense RNA sequence (IRAS) that when injected into the hypothalamus selectively decreases IR signaling in hypothalamus, resulting in increased body weight, peripheral adiposity and plasma leptin levels. To test the hypothesis that this obesity/hyperleptinemic phenotype would impair hippocampal synaptic transmission, we examined short term potentiation (STP) and long term potentiation (LTP) in the hippocampus of rats that received the LV-IRAS construct or the LV-Control construct in the hypothalamus (hypo-IRAS and hypo-Con, respectively). Stimulation of the Schaffer collaterals elicits STP that develops into LTP in the CA1 region of hypo-Con rats; conversely, hypo-IRAS rats exhibit STP that fails to develop into LTP. To more closely examine the potential role of hyperleptinemia in these electrophysiological deficits, hypo-IRAS were subjected to mild food restriction paradigms that would either: 1) prevent the development of the obesity phenotype; or 2) reverse an established obesity phenotype in hypo-IRAS rats. Both of these paradigms restored LTP in the CA1 region and reversed the decreases in the phosphorylated/total ratio of GluA1 Ser845 AMPA receptor subunit expression observed in the hippocampus of hypo-IRAS rats. Collectively, these data support the hypothesis that obesity impairs hippocampal synaptic transmission and support the hypothesis that these deficits are mediated through the impairment of hippocampal leptin activity. PMID:21036186

  3. New brittle bone disorder: report of a family with six affected individuals.

    PubMed

    Nishimura, G; Haga, N; Aoki, K; Hamazaki, M; Taniguchi, K; Iwaya, T

    1999-06-01

    We report on a family in which four females and two males in three generations had a previously undescribed brittle bone disorder that was dominantly transmitted through a maternal line. The cardinal manifestations of the disorder comprised dolichocephaly with frontal bossing, hypoplasia of the midface, postpubertal prognathism, micromelic short stature, coarse trabeculae of the entire skeleton, and bone fragility of variable degrees. Mild spondylar modification and iliac hypoplasia were other hallmarks that were recognized in childhood. The proband, a 19-year-old male, was most severely affected with multiple wormian bones in the calvaria, repetitive fractures, intractable bowing of the legs and forearms, and pseudofractures of the long bones with metaphyseal narrowing. His male cousin was next severely affected with angular deformity restricted to the forearm. The four females were much less affected without angular deformity. The mode of inheritance was thus consistent with either an autosomal dominant trait with sex-influence or an X-linked semidominant trait. Histological bone examination in the proband showed atrophy and fibrous degeneration of the lamellar trabeculae and disorganized chondro-osseous junction, which implied that the disorder involved both intramembranous and enchondral ossifications. PMID:10340645

  4. Suture materials affect peri-implant bone healing and implant osseointegration.

    PubMed

    Villa, Oscar; Lyngstadaas, Staale P; Monjo, Marta; Satué, Maria; Rønold, Hans J; Petzold, Christiane; Wohlfahrt, Johan C

    2015-09-01

    The aim of this study was to evaluate the effects of the remnants of two suture materials on osseointegration of titanium implants in a rabbit tibial model. Calibrated defects were prepared in the tibia of five Chinchilla rabbits. Filaments of nonresorbable (NR) nylon or resorbable (R) chitosan were placed at the bone to implant interface, whereas control sites had no suture material. After a healing period of 4 weeks, a pull-out test procedure was performed followed by enzymatic analyses of the wound fluid and relative quantification of mRNA levels for bone-related and cytokine markers from the peri-implant bone. A trend toward a reduced pull-out force was observed in the NR group (NR: 23.0 ± 12.8 N; R: 33.9 ± 11.3 N; control: 33.6 ± 24.0 N). Similarly, the bone resorption marker vacuolar type H+-ATPase was increased in the NR group compared with that in the control group (P = 0.041). The R group showed trends for lower alkaline phosphatase activity and osteocalcin expression and higher total protein content and RNA compared with the control group. In this submerged healing model, peri-implant bone healing was marginally affected by the two suture materials tested. However, there was a tendency toward better osseointegration and lower expression of bone resorption markers in the R group compared with the control group. PMID:26369486

  5. Suture locking of isolated internal locking knotless suture anchors is not affected by bone quality

    PubMed Central

    Woodmass, Jarret M; Matthewson, Graeme; Ono, Yohei; Bois, Aaron J; Boorman, Richard S; Lo, Ian KY; Thornton, Gail M

    2015-01-01

    Purpose The purpose of this study was to evaluate the mechanical performance of different suture locking mechanisms including: i) interference fit between the anchor and the bone (eg, 4.5 mm PushLock, 5.5 mm SwiveLock), ii) internal locking mechanism within the anchor itself (eg, 5.5 mm SpeedScrew), or iii) a combination of interference fit and internal locking (eg, 4.5 mm MultiFIX P, 5.5 mm MultiFIX S). Methods Anchors were tested in foam blocks representing normal (20/8 foam) or osteopenic (8/8 foam) bone, using standard suture loops pulled in-line with the anchor to isolate suture locking. Mechanical testing included cyclic testing for 500 cycles from 10 N to 60 N at 60 mm/min, followed by failure testing at 60 mm/min. Displacement after 500 cycles at 60 N, number of cycles at 3 mm displacement, load at 3 mm displacement, and maximum load were evaluated. Results Comparing 8/8 foam to 20/8 foam, load at 3 mm displacement and maximum load were significantly decreased (P<0.05) with decreased bone quality for anchors that, even in part, relied on an interference fit suture locking mechanism (ie, 4.5 mm PushLock, 5.5 mm SwiveLock, 4.5 mm MultiFIX P, 5.5 mm MultiFIX S). Bone quality did not affect the mechanical performance of 5.5 mm SpeedScrew anchors which have an isolated internal locking mechanism. Conclusion The mechanical performance of anchors that relied, even in part, on interference fit were affected by bone quality. Isolated internal locking knotless suture anchors functioned independently of bone quality. Anchors with a combined type (interference fit and internal locking) suture locking mechanism demonstrated similar mechanical performance to isolated internal locking anchors in osteopenic foam comparing similar sized anchors. Clinical relevance In osteopenic bone, knotless suture anchors that have an internal locking mechanism (isolated or combined type) may be advantageous for secure tendon fixation to bone. PMID:26124683

  6. The Cultivation of Bt Corn Producing Cry1Ac Toxins Does Not Adversely Affect Non-Target Arthropods

    PubMed Central

    Guo, Yanyan; Feng, Yanjie; Ge, Yang; Tetreau, Guillaume; Chen, Xiaowen; Dong, Xuehui; Shi, Wangpeng

    2014-01-01

    Transgenic corn producing Cry1Ac toxins from Bacillus thuringiensis (Bt) provides effective control of Asian corn borer, Ostrinia furnacalis (Guenée), and thus reduces insecticide applications. However, whether Bt corn exerts undesirable effects on non-target arthropods (NTAs) is still controversial. We conducted a 2-yr study in Shangzhuang Agricultural Experiment Station to assess the potential impact of Bt corn on field population density, biodiversity, community composition and structure of NTAs. On each sampling date, the total abundance, Shannon's diversity index, Pielou's evenness index and Simpson's diversity index were not significantly affected by Bt corn as compared to non-Bt corn. The “sampling dates” had a significant effect on these indices, but no clear tendencies related to “Bt corn” or “sampling dates X corn variety” interaction were recorded. Principal response curve analysis of variance indicated that Bt corn did not alter the distribution of NTAs communities. Bray-Curtis dissimilarity and distance analysis showed that Cry1Ac toxin exposure did not increase community dissimilarities between Bt and non-Bt corn plots and that the evolution of non-target arthropod community was similar on the two corn varieties. The cultivation of Bt corn failed to show any detrimental evidence on the density of non-target herbivores, predators and parasitoids. The composition of herbivores, predators and parasitoids was identical in Bt and non-Bt corn plots. Taken together, results from the present work support that Bt corn producing Cry1Ac toxins does not adversely affect NTAs. PMID:25437213

  7. Human Apolipoprotein E Isoforms differentially affect Bone Mass and Turnover in vivo

    PubMed Central

    Dieckmann, Marco; Beil, F. Timo; Mueller, Brigitte; Bartelt, Alexander; Marshall, Robert P.; Koehne, Till; Amling, Michael; Ruether, Wolfgang; Cooper, Jackie A.; Humphries, Steve E.; Herz, Joachim; Niemeier, Andreas

    2012-01-01

    The primary role of apolipoprotein E (apoE) is to mediate the cellular uptake of lipoproteins. However, a new role for apoE as a regulator of bone metabolism in mice has recently been established. In contrast to mice, the human APOE gene is characterized by three common isoforms APOE ε2, ε3 and ε4 that result in different metabolic properties of the apoE isoforms, but it remains controversial whether the APOE polymorphism influences bone traits in humans. To clarify this, we investigated bone phenotypes of apoE knock-in mice, which express one human isoform each (apoE2 k.i., apoE3 k.i., apoE4 k.i.) in place of the mouse apoE. Analysis of 12 week-old female knock-in mice revealed increased levels of biochemical bone formation and resorption markers in apoE2 k.i. animals as compared to apoE3 k.i. and apoE4 k.i., with a reduced OPG/RANKL ratio in apoE2 k.i., indicating increased turnover with prevailing resorption in apoE2 k.i.. Accordingly, histomorphometric and μCT analyses demonstrated significantly lower trabecular bone mass in apoE2 than in apoE3 and apoE4 k.i. animals, which was reflected by a significant reduction of lumbar vertebrae maximum force resistance. Unlike trabecular bone, femoral cortical thickness, and stability was not differentially affected by the apoE isoforms. To extend these observations to the human situation, plasma from middle-aged healthy men homozygous for ε2/ε2, ε3/ε3, and ε4/ε4 (n=21, n=80, n=55 respectively) was analyzed with regard to bone turnover markers. In analogy to apoE2 k.i. mice, a lower OPG/RANKL ratio was observed in the serum of ε2/ε2 carriers as compared to ε3/ε3 and ε4/ε4 individuals (p=0.02 for ε2/ε2 vs ε4/ε4). In conclusion, the current data strongly underline the general importance of apoE as a regulator of bone metabolism and identifies the APOE ε2 allele as a potential genetic risk factor for low trabecular bone mass and vertebral fractures in humans. PMID:22991192

  8. Electromagnetic fields do not affect bone micro-architecture in osteoporotic rats

    PubMed Central

    van der Jagt, O. P.; van der Linden, J. C.; Waarsing, J. H.; Verhaar, J. A. N.; Weinans, H.

    2014-01-01

    Objectives Electromagnetic fields (EMF) are widely used in musculoskeletal disorders. There are indications that EMF might also be effective in the treatment of osteoporosis. To justify clinical follow-up experiments, we examined the effects of EMF on bone micro-architectural changes in osteoporotic and healthy rats. Moreover, we tested the effects of EMF on fracture healing. Methods EMF (20 Gauss) was examined in rats (aged 20 weeks), which underwent an ovariectomy (OVX; n = 8) or sham-ovariectomy (sham-OVX; n = 8). As a putative positive control, all rats received bilateral fibular osteotomies to examine the effects on fracture healing. Treatment was applied to one proximal lower leg (three hours a day, five days a week); the lower leg was not treated and served as a control. Bone architectural changes of the proximal tibia and bone formation around the osteotomy were evaluated using in vivo microCT scans at start of treatment and after three and six weeks. Results In both OVX and sham-OVX groups, EMF did not result in cancellous or cortical bone changes during follow-up. Moreover, EMF did not affect the amount of mineralised callus volume around the fibular osteotomy. Conclusions In this study we were unable to reproduce the strong beneficial findings reported by others. This might indicate that EMF treatment is very sensitive to the specific set-up, which would be a serious hindrance for clinical use. No evidence was found that EMF treatment can influence bone mass for the benefit of osteoporotic patients. Cite this article: Bone Joint Res 2014;3:230–5. PMID:25015993

  9. Ameloblastin, an Extracellular Matrix Protein, Affects Long Bone Growth and Mineralization.

    PubMed

    Lu, Xuanyu; Fukumoto, Satoshi; Yamada, Yoshihiko; Evans, Carla A; Diekwisch, Thomas Gh; Luan, Xianghong

    2016-06-01

    Matrix molecules such as the enamel-related calcium-binding phosphoprotein ameloblastin (AMBN) are expressed in multiple tissues, including teeth, bones, and cartilage. Here we have asked whether AMBN is of functional importance for timely long bone development and, if so, how it exerts its function related to osteogenesis. Adolescent AMBN-deficient mice (AMBN(Δ5-6) ) suffered from a 33% to 38% reduction in femur length and an 8.4% shorter trunk spinal column when compared with WT controls, whereas there was no difference between adult animals. On a cellular level, AMBN truncation resulted in a shortened growth plate and a 41% to 49% reduction in the number of proliferating tibia chondrocytes and osteoblasts. Bone marrow stromal cells (BMSCs) isolated from AMBN mutant mice displayed defects in proliferation and differentiation potential as well as cytoskeleton organization. Osteogenesis-related growth factors, such as insulin-like growth factor 1 (IGF1) and BMP7, were also significantly (46% to 73%) reduced in AMBN-deficient BMSCs. Addition of exogenous AMBN restored cytoskeleton structures in AMBN mutant BMSCs and resulted in a dramatic 400% to 600% increase in BMP2, BMP7, and Col1A expression. Block of RhoA diminished the effect of AMBN on osteogenic growth factor and matrix protein gene expression. Addition of exogenous BMP7 and IGF1 rescued the proliferation and differentiation potential of AMBN-deficient BMSCs. Confirming the effects of AMBN on long bone growth, back-crossing of mutant mice with full-length AMBN overexpressors resulted in a complete rescue of AMBN(Δ5-6) bone defects. Together, these data indicate that AMBN affects extracellular matrix production and cell adhesion properties in the long bone growth plate, resulting in altered cytoskeletal dynamics, increased osteogenesis-related gene expression, as well as osteoblast and chondrocyte proliferation. We propose that AMBN facilitates rapid long bone growth and an important growth spurt during the

  10. Black bear femoral geometry and cortical porosity are not adversely affected by ageing despite annual periods of disuse (hibernation)

    PubMed Central

    McGee, Meghan E; Miller, Danielle L; Auger, Janene; Black, Hal L; Donahue, Seth W

    2007-01-01

    Disuse (i.e. inactivity) causes bone loss, and a recovery period that is 2–3 times longer than the inactive period is usually required to recover lost bone. However, black bears experience annual disuse (hibernation) and remobilization periods that are approximately equal in length, yet bears maintain or increase cortical bone material properties and whole bone mechanical properties with age. In this study, we investigated the architectural properties of bear femurs to determine whether cortical structure is preserved with age in bears. We showed that cross-sectional geometric properties increase with age, but porosity and resorption cavity density do not change with age in skeletally immature male and female bears. These findings suggest that structural properties substantially contribute to increasing whole bone strength with age in bears, particularly during skeletal maturation. Porosity was not different between skeletally immature and mature bears, and showed minimal regional variations between anatomical quadrants and radial positions that were similar in pattern and magnitude between skeletally immature and mature bears. We also found gender dimorphisms in bear cortical bone properties: females have smaller, less porous bones than males. Our results provide further support for the idea that black bears possess a biological mechanism to prevent disuse osteoporosis. PMID:17261138

  11. Increased Fracture Collapse after Intertrochanteric Fractures Treated by the Dynamic Hip Screw Adversely Affects Walking Ability but Not Survival

    PubMed Central

    Fang, Christian; Gudushauri, Paata; Wong, Tak-Man; Lau, Tak-Wing; Pun, Terence; Leung, Frankie

    2016-01-01

    In osteoporotic hip fractures, fracture collapse is deliberately allowed by commonly used implants to improve dynamic contact and healing. The muscle lever arm is, however, compromised by shortening. We evaluated a cohort of 361 patients with AO/OTA 31.A1 or 31.A2 intertrochanteric fracture treated by the dynamic hip screw (DHS) who had a minimal follow-up of 3 months and an average follow-up of 14.6 months and long term survival data. The amount of fracture collapse and shortening due to sliding of the DHS was determined at the latest follow-up and graded as minimal (<1 cm), moderate (1-2 cm), or severe (>2 cm). With increased severity of collapse, more patients were unable to maintain their premorbid walking function (minimal collapse = 34.2%, moderate = 33.3%, severe = 62.8%, and p = 0.028). Based on ordinal regression of risk factors, increased fracture collapse was significantly and independently related to increasing age (p = 0.037), female sex (p = 0.024), A2 fracture class (p = 0.010), increased operative duration (p = 0.011), poor reduction quality (p = 0.000), and suboptimal tip-apex distance of >25 mm (p = 0.050). Patients who had better outcome in terms of walking function were independently predicted by younger age (p = 0.036), higher MMSE marks (p = 0.000), higher MBI marks (p = 0.010), better premorbid walking status (p = 0.000), less fracture collapse (p = 0.011), and optimal lag screw position in centre-centre or centre-inferior position (p = 0.020). According to Kaplan-Meier analysis, fracture collapse had no association with mortality from 2.4 to 7.6 years after surgery. In conclusion, increased fracture collapse after fixation of geriatric intertrochanteric fractures adversely affected walking but not survival. PMID:26955637

  12. Increased Fracture Collapse after Intertrochanteric Fractures Treated by the Dynamic Hip Screw Adversely Affects Walking Ability but Not Survival.

    PubMed

    Fang, Christian; Gudushauri, Paata; Wong, Tak-Man; Lau, Tak-Wing; Pun, Terence; Leung, Frankie

    2016-01-01

    In osteoporotic hip fractures, fracture collapse is deliberately allowed by commonly used implants to improve dynamic contact and healing. The muscle lever arm is, however, compromised by shortening. We evaluated a cohort of 361 patients with AO/OTA 31.A1 or 31.A2 intertrochanteric fracture treated by the dynamic hip screw (DHS) who had a minimal follow-up of 3 months and an average follow-up of 14.6 months and long term survival data. The amount of fracture collapse and shortening due to sliding of the DHS was determined at the latest follow-up and graded as minimal (<1 cm), moderate (1-2 cm), or severe (>2 cm). With increased severity of collapse, more patients were unable to maintain their premorbid walking function (minimal collapse = 34.2%, moderate = 33.3%, severe = 62.8%, and p = 0.028). Based on ordinal regression of risk factors, increased fracture collapse was significantly and independently related to increasing age (p = 0.037), female sex (p = 0.024), A2 fracture class (p = 0.010), increased operative duration (p = 0.011), poor reduction quality (p = 0.000), and suboptimal tip-apex distance of >25 mm (p = 0.050). Patients who had better outcome in terms of walking function were independently predicted by younger age (p = 0.036), higher MMSE marks (p = 0.000), higher MBI marks (p = 0.010), better premorbid walking status (p = 0.000), less fracture collapse (p = 0.011), and optimal lag screw position in centre-centre or centre-inferior position (p = 0.020). According to Kaplan-Meier analysis, fracture collapse had no association with mortality from 2.4 to 7.6 years after surgery. In conclusion, increased fracture collapse after fixation of geriatric intertrochanteric fractures adversely affected walking but not survival. PMID:26955637

  13. Neonatal and fetal exposure to trans-fatty acid retards early growth and adiposity while adversely affecting glucose in mice

    PubMed Central

    Kavanagh, Kylie; Sajadian, Soraya; Jenkins, Kurt A.; Wilson, Martha D.; Carr, J. Jeffery; Wagner, Janice D.; Rudel, Lawrence L.

    2010-01-01

    Industrially produced trans fatty acids (TFAs) consumed in western diets are incorporated into maternal and fetal tissues, and are passed linearly to offspring via breast milk. We hypothesized that TFA exposure in utero and during lactation in infants would promote obesity and poor glycemic control as compared to unmodified fatty acids. We further hypothesized that in utero exposure alone may program for these outcomes in adulthood. To test this hypothesis we fed female C57/BL6 mice identical western diets that differed only in cis- or trans-isomers of C18:1 and then aimed to determine whether maternal transfer of TFAs through pregnancy and lactation alters growth, body composition and glucose metabolism. Mice were unexposed, exposed during pregnancy, during lactation, or throughout pregnancy and lactation to TFA. Body weight and composition (by computed tomography), and glucose metabolism we assessed at weaning and adulthood. TFA exposure through breast milk caused significant early growth retardation (p<0.001) and higher fasting glucose (p=0.01) but insulin sensitivity was not different. Elevated plasma insulin-like growth factor-1 in mice consuming TFA-enriched milk (p=0.02) may contribute to later catch-up growth, leanness and preserved peripheral insulin sensitivity observed in these mice. Mice exposed to TFA in utero underwent rapid early neonatal growth with TFA-free breast milk and had significantly impaired insulin sensitivity (p<0.05) and greater abdominal fat (p=0.01). We conclude that very early catch-up growth resulted in impaired peripheral insulin sensitivity in this model of diet-related fetal and neonatal programming. TFA surprisingly retarded growth and adiposity while still adversely affecting glucose metabolism. PMID:20650350

  14. Extreme Air Pollution Conditions Adversely Affect Blood Pressure and Insulin Resistance: The Air Pollution and Cardiometabolic Disease Study.

    PubMed

    Brook, Robert D; Sun, Zhichao; Brook, Jeffrey R; Zhao, Xiaoyi; Ruan, Yanping; Yan, Jianhua; Mukherjee, Bhramar; Rao, Xiaoquan; Duan, Fengkui; Sun, Lixian; Liang, Ruijuan; Lian, Hui; Zhang, Shuyang; Fang, Quan; Gu, Dongfeng; Sun, Qinghua; Fan, Zhongjie; Rajagopalan, Sanjay

    2016-01-01

    Mounting evidence supports that fine particulate matter adversely affects cardiometabolic diseases particularly in susceptible individuals; however, health effects induced by the extreme concentrations within megacities in Asia are not well described. We enrolled 65 nonsmoking adults with metabolic syndrome and insulin resistance in the Beijing metropolitan area into a panel study of 4 repeated visits across 4 seasons since 2012. Daily ambient fine particulate matter and personal black carbon levels ranged from 9.0 to 552.5 µg/m(3) and 0.2 to 24.5 µg/m(3), respectively, with extreme levels observed during January 2013. Cumulative fine particulate matter exposure windows across the prior 1 to 7 days were significantly associated with systolic blood pressure elevations ranging from 2.0 (95% confidence interval, 0.3-3.7) to 2.7 (0.6-4.8) mm Hg per SD increase (67.2 µg/m(3)), whereas cumulative black carbon exposure during the previous 2 to 5 days were significantly associated with ranges in elevations in diastolic blood pressure from 1.3 (0.0-2.5) to 1.7 (0.3-3.2) mm Hg per SD increase (3.6 µg/m(3)). Both black carbon and fine particulate matter were significantly associated with worsening insulin resistance (0.18 [0.01-0.36] and 0.22 [0.04-0.39] unit increase per SD increase of personal-level black carbon and 0.18 [0.02-0.34] and 0.22 [0.08-0.36] unit increase per SD increase of ambient fine particulate matter on lag days 4 and 5). These results provide important global public health warnings that air pollution may pose a risk to cardiometabolic health even at the extremely high concentrations faced by billions of people in the developing world today. PMID:26573709

  15. Hydroxyapatite crystallinity does not affect the repair of critical size bone defects

    PubMed Central

    CONZ, Marcio Baltazar; GRANJEIRO, José Mauro; SOARES, Gloria de Almeida

    2011-01-01

    Objective The physicochemical properties of hydroxyapatite (HA) granules were observed to affect the biological behavior of graft materials. The aim of this work was to analyze the tissue response of two HA granules with different crystallinity and Ca/P ratio in vivo. Material and Methods The HA granules were produced in the Biomaterials Laboratory (COPPE/UFRJ). The testing materials were HA granules presenting a Ca/P molar ratio of 1.60 and 28% crystallinity (HA-1), and a Ca/P molar ratio of 1.67 and 70% crystallinity (HA-2). Both HAs were implanted into a critical-size calvaria rat defects. Results To note, in the control group, the bone defects were filled with blood clot only. Descriptive and histomorphometric analyses after 1, 3, and 6 months postoperatively showed mild inflammatory infiltrate, mainly comprising macrophage-like and multinucleated giant cells, and an increase in the volume density of the fibrous tissues (p<0.05), which was in contrast to the similar volume density of the newly formed bone and biomaterials in relation to the control group. Conclusion Thus, we concluded that HA-1 and HA-2 are biocompatible and non-degradable, and that crystallinity does not affect bone repair of critical size defects. PMID:21655775

  16. Zebrafish Bone and General Physiology Are Differently Affected by Hormones or Changes in Gravity

    PubMed Central

    Aceto, Jessica; Nourizadeh-Lillabadi, Rasoul; Marée, Raphael; Dardenne, Nadia; Jeanray, Nathalie; Wehenkel, Louis; Aleström, Peter

    2015-01-01

    Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire organism is still incomplete. We used altered gravity and drug treatment experiments to evaluate their effects specifically on bone formation and more generally on whole genome gene expression. By combining morphometric tools with an objective scoring system for the state of development for each element in the head skeleton and specific gene expression analysis, we confirmed and characterized in detail the decrease or increase of bone formation caused by a 5 day treatment (from 5dpf to 10 dpf) of, respectively parathyroid hormone (PTH) or vitamin D3 (VitD3). Microarray transcriptome analysis after 24 hours treatment reveals a general effect on physiology upon VitD3 treatment, while PTH causes more specifically developmental effects. Hypergravity (3g from 5dpf to 9 dpf) exposure results in a significantly larger head and a significant increase in bone formation for a subset of the cranial bones. Gene expression analysis after 24 hrs at 3g revealed differential expression of genes involved in the development and function of the skeletal, muscular, nervous, endocrine and cardiovascular systems. Finally, we propose a novel type of experimental approach, the "Reduced Gravity Paradigm", by keeping the developing larvae at 3g hypergravity for the first 5 days before returning them to 1g for one additional day. 5 days exposure to 3g during these early stages also caused increased bone formation, while gene expression analysis revealed a central network of regulatory genes (hes5, sox10, lgals3bp, egr1, edn1, fos, fosb, klf2, gadd45ba and socs3a) whose expression was consistently affected by the transition from hyper- to normal gravity. PMID:26061167

  17. Zebrafish Bone and General Physiology Are Differently Affected by Hormones or Changes in Gravity.

    PubMed

    Aceto, Jessica; Nourizadeh-Lillabadi, Rasoul; Marée, Raphael; Dardenne, Nadia; Jeanray, Nathalie; Wehenkel, Louis; Aleström, Peter; van Loon, Jack J W A; Muller, Marc

    2015-01-01

    Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire organism is still incomplete. We used altered gravity and drug treatment experiments to evaluate their effects specifically on bone formation and more generally on whole genome gene expression. By combining morphometric tools with an objective scoring system for the state of development for each element in the head skeleton and specific gene expression analysis, we confirmed and characterized in detail the decrease or increase of bone formation caused by a 5 day treatment (from 5dpf to 10 dpf) of, respectively parathyroid hormone (PTH) or vitamin D3 (VitD3). Microarray transcriptome analysis after 24 hours treatment reveals a general effect on physiology upon VitD3 treatment, while PTH causes more specifically developmental effects. Hypergravity (3g from 5dpf to 9 dpf) exposure results in a significantly larger head and a significant increase in bone formation for a subset of the cranial bones. Gene expression analysis after 24 hrs at 3g revealed differential expression of genes involved in the development and function of the skeletal, muscular, nervous, endocrine and cardiovascular systems. Finally, we propose a novel type of experimental approach, the "Reduced Gravity Paradigm", by keeping the developing larvae at 3g hypergravity for the first 5 days before returning them to 1g for one additional day. 5 days exposure to 3g during these early stages also caused increased bone formation, while gene expression analysis revealed a central network of regulatory genes (hes5, sox10, lgals3bp, egr1, edn1, fos, fosb, klf2, gadd45ba and socs3a) whose expression was consistently affected by the transition from hyper- to normal gravity. PMID:26061167

  18. Bone density and anisotropy affect periprosthetic cement and bone stresses after anatomical glenoid replacement: A micro finite element analysis.

    PubMed

    Chevalier, Yan; Santos, Inês; Müller, Peter E; Pietschmann, Matthias F

    2016-06-14

    Glenoid loosening is still a main complication for shoulder arthroplasty. We hypothesize that cement and bone stresses potentially leading to fixation failure are related not only to glenohumeral conformity, fixation design or eccentric loading, but also to bone volume fraction, cortical thickness and degree of anisotropy in the glenoid. In this study, periprosthetic bone and cement stresses were computed with micro finite element models of the replaced glenoid depicting realistic bone microstructure. These models were used to quantify potential effects of bone microstructural parameters under loading conditions simulating different levels of glenohumeral conformity and eccentric loading simulating glenohumeral instability. Results show that peak cement stresses were achieved near the cement-bone interface in all loading schemes. Higher stresses within trabecular bone tissue and cement mantle were obtained within specimens of lower bone volume fraction and in regions of low anisotropy, increasing with decreasing glenohumeral conformity and reaching their maxima below the keeled design when the load is shifted superiorly. Our analyses confirm the combined influences of eccentric load shifts with reduced bone volume fraction and anisotropy on increasing periprosthetic stresses. They finally suggest that improving fixation of glenoid replacements must reduce internal cement and bone tissue stresses, in particular in glenoids of low bone density and heterogeneity. PMID:27087675

  19. Do social disadvantage and early family adversity affect the diurnal cortisol rhythm in infants? The Generation R Study.

    PubMed

    Saridjan, Nathalie S; Huizink, Anja C; Koetsier, Jitske A; Jaddoe, Vincent W; Mackenbach, Johan P; Hofman, Albert; Kirschbaum, Clemens; Verhulst, Frank C; Tiemeier, Henning

    2010-02-01

    Dysregulation of diurnal cortisol secretion patterns may explain the link between adversities early in life and later mental health problems. However, few studies have investigated the influence of social disadvantage and family adversity on the hypothalamic-pituitary-adrenal (HPA) axis early in life. In 366 infants aged 12-20 months from the Generation R Study, a population-based cohort from fetal life onwards, parents collected saliva samples from their infant at 5 moments over the course of 1 day. The area under the curve (AUC), the cortisol awakening response (CAR) and the diurnal cortisol slope were calculated as different composite measures of the diurnal cortisol rhythm. Information about social disadvantage and early adversity was collected using prenatal and postnatal questionnaires. We found that older infants showed lower AUC levels; moreover, infants with a positive CAR were significantly older. Both the AUC and the CAR were related to indicators of social disadvantage and early adversity. Infants of low income families, in comparison to high income families, showed higher AUC levels and a positive CAR. Infants of mothers who smoked during pregnancy were also significantly more likely to show a positive CAR. Furthermore, infants of mothers experiencing parenting stress showed higher AUC levels. The results of our study show that effects of social disadvantage and early adversity on the diurnal cortisol rhythm are already observable in infants. This may reflect the influence of early negative life events on early maturation of the HPA axis. PMID:20006614

  20. Morbid obesity in liver transplant recipients adversely affects longterm graft and patient survival in a single-institution analysis

    PubMed Central

    Conzen, Kendra D; Vachharajani, Neeta; Collins, Kelly M; Anderson, Christopher D; Lin, Yiing; Wellen, Jason R; Shenoy, Surendra; Lowell, Jeffrey A; Doyle, M B Majella; Chapman, William C

    2015-01-01

    Objective The effects of obesity in liver transplantation remain controversial. Earlier institutional data demonstrated no significant difference in postoperative complications or 1-year mortality. This study was conducted to test the hypothesis that obesity alone has minimal effect on longterm graft and overall survival. Methods A retrospective, single-institution analysis of outcomes in patients submitted to primary adult orthotopic liver transplantation was conducted using data for the period from 1 January 2002 to 31 December 2012. Recipients were divided into six groups by pre-transplant body mass index (BMI), comprising those with BMIs of <18.0 kg/m2, 18.0–24.9 kg/m2, 25.0–29.9 kg/m2, 30.0–35.0 kg/m2, 35.1–40.0 kg/m2 and >40 kg/m2, respectively. Pre- and post-transplant parameters were compared. A P-value of <0.05 was considered to indicate statistical significance. Independent predictors of patient and graft survival were determined using multivariate analysis. Results A total of 785 patients met the study inclusion criteria. A BMI of >35 kg/m2 was associated with non-alcoholic steatohepatitis (NASH) cirrhosis (P < 0.0001), higher Model for End-stage Liver Disease (MELD) score, and longer wait times for transplant (P = 0.002). There were no differences in operative time, intensive care unit or hospital length of stay, or perioperative complications. Graft and patient survival at intervals up to 3 years were similar between groups. Compared with non-obese recipients, recipients with a BMI of >40 kg/m2 showed significantly reduced 5-year graft (49.0% versus 75.8%; P < 0.02) and patient (51.3% versus 78.8%; P < 0.01) survival. Conclusions Obesity increasingly impacts outcomes in liver transplantation. Although the present data are limited by the fact that they were sourced from a single institution, they suggest that morbid obesity adversely affects longterm outcomes despite providing similar short-term results. Further analysis is

  1. Minimum Pricing of Alcohol versus Volumetric Taxation: Which Policy Will Reduce Heavy Consumption without Adversely Affecting Light and Moderate Consumers?

    PubMed Central

    Sharma, Anurag; Vandenberg, Brian; Hollingsworth, Bruce

    2014-01-01

    Background We estimate the effect on light, moderate and heavy consumers of alcohol from implementing a minimum unit price for alcohol (MUP) compared with a uniform volumetric tax. Methods We analyse scanner data from a panel survey of demographically representative households (n = 885) collected over a one-year period (24 Jan 2010–22 Jan 2011) in the state of Victoria, Australia, which includes detailed records of each household's off-trade alcohol purchasing. Findings The heaviest consumers (3% of the sample) currently purchase 20% of the total litres of alcohol (LALs), are more likely to purchase cask wine and full strength beer, and pay significantly less on average per standard drink compared to the lightest consumers (A$1.31 [95% CI 1.20–1.41] compared to $2.21 [95% CI 2.10–2.31]). Applying a MUP of A$1 per standard drink has a greater effect on reducing the mean annual volume of alcohol purchased by the heaviest consumers of wine (15.78 LALs [95% CI 14.86–16.69]) and beer (1.85 LALs [95% CI 1.64–2.05]) compared to a uniform volumetric tax (9.56 LALs [95% CI 9.10–10.01] and 0.49 LALs [95% CI 0.46–0.41], respectively). A MUP results in smaller increases in the annual cost for the heaviest consumers of wine ($393.60 [95% CI 374.19–413.00]) and beer ($108.26 [95% CI 94.76–121.75]), compared to a uniform volumetric tax ($552.46 [95% CI 530.55–574.36] and $163.92 [95% CI 152.79–175.03], respectively). Both a MUP and uniform volumetric tax have little effect on changing the annual cost of wine and beer for light and moderate consumers, and likewise little effect upon their purchasing. Conclusions While both a MUP and a uniform volumetric tax have potential to reduce heavy consumption of wine and beer without adversely affecting light and moderate consumers, a MUP offers the potential to achieve greater reductions in heavy consumption at a lower overall annual cost to consumers. PMID:24465368

  2. Benefits of adversity?! How life history affects the behavioral profile of mice varying in serotonin transporter genotype

    PubMed Central

    Bodden, Carina; Richter, S. Helene; Schreiber, Rebecca S.; Kloke, Vanessa; Gerß, Joachim; Palme, Rupert; Lesch, Klaus-Peter; Lewejohann, Lars; Kaiser, Sylvia; Sachser, Norbert

    2015-01-01

    Behavioral profiles are influenced by both positive and negative experiences as well as the genetic disposition. Traditionally, accumulating adversity over lifetime is considered to predict increased anxiety-like behavior (“allostatic load”). The alternative “mismatch hypothesis” suggests increased levels of anxiety if the early environment differs from the later-life environment. Thus, there is a need for a whole-life history approach to gain a deeper understanding of how behavioral profiles are shaped. The aim of this study was to elucidate the effects of life history on the behavioral profile of mice varying in serotonin transporter (5-HTT) genotype, an established mouse model of increased anxiety-like behavior. For this purpose, mice grew up under either adverse or beneficial conditions during early phases of life. In adulthood, they were further subdivided so as to face a situation that either matched or mismatched the condition experienced so far, resulting in four different life histories. Subsequently, mice were tested for their anxiety-like and exploratory behavior. The main results were: (1) Life history profoundly modulated the behavioral profile. Surprisingly, mice that experienced early beneficial and later escapable adverse conditions showed less anxiety-like and more exploratory behavior compared to mice of other life histories. (2) Genotype significantly influenced the behavioral profile, with homozygous 5-HTT knockout mice displaying highest levels of anxiety-like and lowest levels of exploratory behavior. Our findings concerning life history indicate that the absence of adversity does not necessarily cause lower levels of anxiety than accumulating adversity. Rather, some adversity may be beneficial, particularly when following positive events. Altogether, we conclude that for an understanding of behavioral profiles, it is not sufficient to look at experiences during single phases of life, but the whole life history has to be considered

  3. Oral contraceptive use by teenage women does not affect peak bone mass: a longitudinal study.

    PubMed

    Lloyd, T; Taylor, D S; Lin, H M; Matthews, A E; Eggli, D F; Legro, R S

    2000-10-01

    This longitudinal observational study determined the effect of oral contraceptive (OC) use during adolescence on peak bone mass (PBM). The sample comprised 62 non-Hispanic, White females in The Penn State Young Women's Health Study, who were studied for 8 years between the ages of 12 and 20. There were 28 OC users who used OCs for a minimum of 6 months and were still using them at age 20, and 34 nonusers who had never used the regimen. Total body bone, dedicated hipbone, and body composition measurements were made by dual-energy roentgenogram absorptiometry. There was no difference between OC users and nonusers in the anthropometric, body composition, or total body bone measurements. By age 20, the average duration of OC use by the user group was 22 months. At this age, the groups remained indistinguishable in anthropometric, body composition, total body, and hipbone measurements, and in age of menarche and sports exercise scores. These findings suggest that OC use by healthy, White, teenage females does not affect acquisition of PBM. PMID:11020515

  4. Kinin B1 Receptor Deletion Affects Bone Healing in Type 1 Diabetic Mice.

    PubMed

    Cignachi, Natália P; Pesquero, João B; Oliveira, Rogério B; Etges, Adriana; Campos, Maria M

    2015-12-01

    The effects of kinin B1 receptor (B1 R) deletion were examined on femur bone regeneration in streptozotocin (STZ)-type 1 diabetes. Diabetes induction in wild-type C57/BL6 (WTC57BL6) mice led to decrease in body weight and hyperglycemia, compared to the non-diabetic group of the same strain. The lack of B1 R did not affect STZ-elicited body weight loss, but partially prevented hyperglycemia. Diabetic mice had a clear delay in bone regeneration, and displayed large areas of loose connective tissue within the defects, with a reduced expression of the mineralization-related protein osteonectin, when compared to the non-diabetic WTC57/BL6. The non-diabetic and diabetic B1 R knockout (B1 RKO) mice had bone regeneration levels and osteonectin expression comparable to that seen in control WTC57/BL6 mice. WTC57/BL6 STZ-diabetic mice also showed a marked reduction of collagen contents, with increased immunolabeling for the apoptosis marker caspase-3, whereas diabetic B1 RKO had collagen levels and caspase-3 activity comparable to those observed in non-diabetic WTC57/BL6 or B1 RKO mice. No significant difference was detected in the number of tartrate-resistant acid phosphatase (TRAP)-stained cells, or in RANK/RANKL/OPG system immunolabeling throughout the experimental groups. Data bring novel evidence on the relevance of kinin B1 R under type 1 diabetes with regards to its role in bone regeneration. PMID:25969420

  5. A supra-cellular model for coupling of bone resorption to formation during remodeling: lessons from two bone resorption inhibitors affecting bone formation differently.

    PubMed

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Pennypacker, Brenda L; Duong, Le T; Engelholm, Lars H; Delaissé, Jean-Marie

    2014-01-10

    The bone matrix is maintained functional through the combined action of bone resorbing osteoclasts and bone forming osteoblasts, in so-called bone remodeling units. The coupling of these two activities is critical for securing bone replenishment and involves osteogenic factors released by the osteoclasts. However, the osteoclasts are separated from the mature bone forming osteoblasts in time and space. Therefore the target cell of these osteoclastic factors has remained unknown. Recent explorations of the physical microenvironment of osteoclasts revealed a cell layer lining the bone marrow and forming a canopy over the whole remodeling surface, spanning from the osteoclasts to the bone forming osteoblasts. Several observations show that these canopy cells are a source of osteoblast progenitors, and we hypothesized therefore that they are the likely cells targeted by the osteogenic factors of the osteoclasts. Here we provide evidence supporting this hypothesis, by comparing the osteoclast-canopy interface in response to two types of bone resorption inhibitors in rabbit lumbar vertebrae. The bisphosphonate alendronate, an inhibitor leading to low bone formation levels, reduces the extent of canopy coverage above osteoclasts. This effect is in accordance with its toxic action on periosteoclastic cells. In contrast, odanacatib, an inhibitor preserving bone formation, increases the extent of the osteoclast-canopy interface. Interestingly, these distinct effects correlate with how fast bone formation follows resorption during these respective treatments. Furthermore, canopy cells exhibit uPARAP/Endo180, a receptor able to bind the collagen made available by osteoclasts, and reported to mediate osteoblast recruitment. Overall these observations support a mechanism where the recruitment of bone forming osteoblasts from the canopy is induced by osteoclastic factors, thereby favoring initiation of bone formation. They lead to a model where the osteoclast-canopy interface is

  6. Bone Tumor

    MedlinePlus

    ... most common types of primary bone cancer are: • Multiple myeloma. Multiple myeloma is the most common primary bone cancer. It ... Any bone can be affected by this cancer. Multiple myeloma affects approximately six people per 100,000 each ...

  7. AGE-RELATED FACTORS AFFECTING THE POST-YIELD ENERGY DISSIPATION OF HUMAN CORTICAL BONE

    PubMed Central

    Nyman, Jeffry S.; Roy, Anuradha; Tyler, Jerrod H.; Acuna, Rae L.; Gayle, Heather J.; Wang, Xiaodu

    2007-01-01

    The risk of bone fracture depends in part on the quality of the tissue, not just the size and mass. This study assessed the post-yield energy dissipation of cortical bone in tension as a function of age and composition. Tensile specimens were prepared from tibiae of human cadavers in which male and female donors were divided into two age groups: middle aged (51 to 56 years old, n = 9) and elderly (72 to 90 years old, n = 8). By loading, unloading, and reloading a specimen with rest period inserted in between, tensile properties at incremental strain levels were assessed. In addition, the post-yield toughness was estimated and partitioned as follows: plastic strain energy related to permanent deformation, released elastic strain energy related to stiffness loss, and hysteresis energy related to viscous behavior. Porosity, mineral and collagen content, and collagen crosslinks of each specimen were also measured to determine the micro and ultrastructural properties of the tissue. It was found that age affected all the energy terms plus strength but not elastic stiffness. The post-yield energy terms were correlated with porosity, pentosidine (a marker of non-enzymatic crosslinks), and collagen content, all of which significantly varied with age. General linear models with the highest possible R2 value suggested that the pentosidine concentration and collagen content provided the best explanation of the age-related decrease in the post-yield energy dissipation of bone. Among them, pentosidine concentration had the greatest contribution to plastic strain energy and was the best explanatory variable of damage accumulation. PMID:17266142

  8. CT and MR imaging findings of systemic complications occurring during pregnancy and puerperal period, adversely affected by natural changes

    PubMed Central

    Himoto, Yuki; Kido, Aki; Moribata, Yusaku; Yamaoka, Toshihide; Okumura, Ryosuke; Togashi, Kaori

    2015-01-01

    Dynamic physiological and anatomical changes for delivery may adversely induce various specific non-obstetric complications during pregnancy and puerperal period. These complications can be fatal to both the mother and the fetus, thus a precise and early diagnosis ensued by an early treatment is essential. Along with ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) have assumed an increasing role in the diagnosis. This article aims to discuss the pathophysiology of these complications, the indications for CT and MRI, and the imaging findings. PMID:26937442

  9. CT and MR imaging findings of systemic complications occurring during pregnancy and puerperal period, adversely affected by natural changes.

    PubMed

    Himoto, Yuki; Kido, Aki; Moribata, Yusaku; Yamaoka, Toshihide; Okumura, Ryosuke; Togashi, Kaori

    2015-01-01

    Dynamic physiological and anatomical changes for delivery may adversely induce various specific non-obstetric complications during pregnancy and puerperal period. These complications can be fatal to both the mother and the fetus, thus a precise and early diagnosis ensued by an early treatment is essential. Along with ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) have assumed an increasing role in the diagnosis. This article aims to discuss the pathophysiology of these complications, the indications for CT and MRI, and the imaging findings. PMID:26937442

  10. Factors affecting the development of adverse drug reactions to β-blockers in hospitalized cardiac patient population

    PubMed Central

    Mugoša, Snežana; Djordjević, Nataša; Djukanović, Nina; Protić, Dragana; Bukumirić, Zoran; Radosavljević, Ivan; Bošković, Aneta; Todorović, Zoran

    2016-01-01

    The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6) poor metabolizer alleles (*3, *4, *5, and *6) on a Montenegrin population and its impact on developing adverse drug reactions (ADRs) of β-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any β-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients’ medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to β-blockers were observed in 15 (10.9%) patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (P<0.001), with ADRs’ occurrence significantly correlating with slower CYP2D6 metabolism. Our study showed that the adverse reactions to β-blockers could be predicted by the length of hospitalization, CYP2D6 poor metabolizer phenotype, and the concomitant use of other CYP2D6-metabolizing drugs. Therefore, in hospitalized patients with polypharmacy CYP2D6 genotyping might be useful in detecting those at risk of ADRs. PMID:27536078

  11. Mode of heparin attachment to nanocrystalline hydroxyapatite affects its interaction with bone morphogenetic protein-2.

    PubMed

    Goonasekera, Chandhi S; Jack, Kevin S; Bhakta, Gajadhar; Rai, Bina; Luong-Van, Emma; Nurcombe, Victor; Cool, Simon M; Cooper-White, Justin J; Grøndahl, Lisbeth

    2015-01-01

    Heparin has a high affinity for bone morphogenetic protein-2 (BMP-2), which is a key growth factor in bone regeneration. The aim of this study was to investigate how the rate of release of BMP-2 was affected when adsorbed to nanosized hydroxyapatite (HAP) particles functionalized with heparin by different methods. Heparin was attached to the surface of HAP, either via adsorption or covalent coupling, via a 3-aminopropyltriethoxysilane (APTES) layer. The chemical composition of the particles was evaluated using X-ray photoelectron spectroscopy and elemental microanalysis, revealing that the heparin grafting densities achieved were dependent on the curing temperature used in the fabrication of APTES-modified HAP. Comparable amounts of heparin were attached via both covalent coupling and adsorption to the APTES-modified particles, but characterization of the particle surfaces by zeta potential and Brunauer-Emmett-Teller measurements indicated that the conformation of the heparin on the surface was dependent on the method of attachment, which in turn affected the stability of heparin on the surface. The release of BMP-2 from the particles after 7 days in phosphate-buffered saline found that 31% of the loaded BMP-2 was released from the APTES-modified particles with heparin covalently attached, compared to 16% from the APTES-modified particles with the heparin adsorbed. Moreover, when heparin was adsorbed onto pure HAP, it was found that the BMP-2 released after 7 days was 5% (similar to that from unmodified HAP). This illustrates that by altering the mode of attachment of heparin to HAP the release profile and total release of BMP-2 can be manipulated. Importantly, the BMP-2 released from all the heparin particle types was found by the SMAD 1/5/8 phosphorylation assay to be biologically active. PMID:26474791

  12. Impaired Glucose Tolerance or Newly Diagnosed Diabetes Mellitus Diagnosed during Admission Adversely Affects Prognosis after Myocardial Infarction: An Observational Study

    PubMed Central

    George, Anish; Bhatia, Raghav T.; Buchanan, Gill L.; Whiteside, Anne; Moisey, Robert S.; Beer, Stephen F.; Chattopadhyay, Sudipta; Sathyapalan, Thozhukat; John, Joseph

    2015-01-01

    Objective To investigate the prognostic effect of newly diagnosed diabetes mellitus (NDM) and impaired glucose tolerance (IGT) post myocardial infarction (MI). Research Design and Methods Retrospective cohort study of 768 patients without preexisting diabetes mellitus post-MI at one centre in Yorkshire between November 2005 and October 2008. Patients were categorised as normal glucose tolerance (NGT n = 337), IGT (n = 279) and NDM (n = 152) on pre- discharge oral glucose tolerance test (OGTT). Primary end-point was the first occurrence of major adverse cardiovascular events (MACE) including cardiovascular death, non-fatal MI, severe heart failure (HF) or non-haemorrhagic stroke. Secondary end-points were all cause mortality and individual components of MACE. Results Prevalence of NGT, impaired fasting glucose (IFG), IGT and NDM changed from 90%, 6%, 0% and 4% on fasting plasma glucose (FPG) to 43%, 1%, 36% and 20% respectively after OGTT. 102 deaths from all causes (79 as first events of which 46 were cardiovascular), 95 non fatal MI, 18 HF and 9 non haemorrhagic strokes occurred during 47.2 ± 9.4 months follow up. Event free survival was lower in IGT and NDM groups. IGT (HR 1.54, 95% CI: 1.06–2.24, p = 0.024) and NDM (HR 2.15, 95% CI: 1.42–3.24, p = 0.003) independently predicted MACE free survival. IGT and NDM also independently predicted incidence of MACE. NDM but not IGT increased the risk of secondary end-points. Conclusion Presence of IGT and NDM in patients presenting post-MI, identified using OGTT, is associated with increased incidence of MACE and is associated with adverse outcomes despite adequate secondary prevention. PMID:26571120

  13. Diabetes mellitus related bone metabolism and periodontal disease

    PubMed Central

    Wu, Ying-Ying; Xiao, E; Graves, Dana T

    2015-01-01

    Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide. Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus. Alveolar bone loss is one of the main outcomes of periodontitis, and diabetes is among the primary risk factors for periodontal disease. In this review, we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects, focusing on alveolar bone loss. Bone remodelling begins with osteoclasts resorbing bone, followed by new bone formation by osteoblasts in the resorption lacunae. Therefore, we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts. PMID:25857702

  14. Glucocorticoids, Osteocytes, and Skeletal Fragility: The Role of Bone Vascularity

    PubMed Central

    Weinstein, Robert S.

    2009-01-01

    Glucocorticoid administration is required for many inflammatory and autoimmune diseases, but use of these drugs is associated with skeletal side effects including bone loss, fractures, and osteonecrosis. Fractures often occur without a reduction in bone mineral density, strongly suggesting that glucocorticoid excess adversely affects other aspects of bone strength. Although the primary effects of glucocorticoid excess on the skeleton are directly on bone cells, a vascular connection between these cells and the loss of bone strength appears likely. This review examines this connection and how it may explain the greater decline in bone strength than loss of bone mass that occurs with glucocorticoid excess. PMID:19591965

  15. Dietary protein level and source differentially affect bone metabolism, strength, and intestinal calcium transporter expression during ad libitum and food-restricted conditions in male rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High protein diets may attenuate bone loss during energy restriction (ER). The objective of the current study was to determine whether high protein diets suppress bone turnover and improve bone quality in rats during ER and whether dietary protein source affects this relationship. Eighty 12-week o...

  16. When the serotonin transporter gene meets adversity: the contribution of animal models to understanding epigenetic mechanisms in affective disorders and resilience.

    PubMed

    Lesch, Klaus-Peter

    2011-01-01

    Although converging epidemiological evidence links exposure to stressful life events with increased risk for affective spectrum disorders, there is extraordinary interindividual variability in vulnerability to adversity. The environmentally moderated penetrance of genetic variation is thought to play a major role in determining who will either develop disease or remain resilient. Research on genetic factors in the aetiology of disorders of emotion regulation has, nevertheless, been complicated by a mysterious discrepancy between high heritability estimates and a scarcity of replicable gene-disorder associations. One explanation for this incongruity is that at least some specific gene effects are conditional on environmental cues, i.e. gene-by-environment interaction (G × E) is present. For example, a remarkable number of studies reported an association of variation in the human serotonin (5-HT) transporter gene (SLC6A4, 5-HTT, SERT) with emotional and cognitive traits as well as increased risk for depression in interaction with psychosocial adversity. The results from investigations in non-human primate and mouse support the occurrence of G × E interaction by showing that variation of 5-HTT function is associated with a vulnerability to adversity across the lifespan leading to unfavourable outcomes resembling various neuropsychiatric disorders. The neural and molecular mechanisms by which environmental adversity in early life increases disease risk in adulthood are not known but may include epigenetic programming of gene expression during development. Epigenetic mechanisms, such as DNA methylation and chromatin modification, are dynamic and reversible and may also provide targets for intervention strategies (see Bountra et al., Curr Top Behav Neurosci, 2011). Animal models amenable to genetic manipulation are useful in the identification of molecular mechanisms underlying epigenetic programming by adverse environments and individual differences in

  17. The type B brevetoxin (PbTx-3) adversely affects development, cardiovascular function, and survival in Medaka (Oryzias latipes) embryos.

    PubMed Central

    Colman, Jamie R; Ramsdell, John S

    2003-01-01

    Brevetoxins are produced by the red tide dinoflagellate Karenia brevis. The toxins are lipophilic polyether toxins that elicit a myriad of effects depending on the route of exposure and the target organism. Brevetoxins are therefore broadly toxic to marine and estuarine animals. By mimicking the maternal route of exposure to the oocytes in finfish, we characterized the adverse effects of the type B brevetoxin brevetoxin-3 (PbTx-3) on embryonic fish development and survival. The Japanese rice fish, medaka (Oryzias latipes), was used as the experimental model in which individual eggs were exposed via microinjection to various known concentrations of PbTx-3 dissolved in an oil vehicle. Embryos injected with doses exceeding 1.0 ng/egg displayed tachycardia, hyperkinetic twitches in the form of sustained convulsions, spinal curvature, clumping of the erythrocytes, and decreased hatching success. Furthermore, fish dosed with toxin were often unable to hatch in the classic tail-first fashion and emerged head first, which resulted in partial hatches and death. We determined that the LD(50) (dose that is lethal to 50% of the fish) for an injected dose of PbTx-3 is 4.0 ng/egg. The results of this study complement previous studies of the developmental toxicity of the type A brevetoxin brevetoxin-1 (PbTx-1), by illustrating in vivo the differing affinities of the two congeners for cardiac sodium channels. Consequently, we observed differing cardiovascular responses in the embryos, wherein embryos exposed to PbTx-3 exhibited persistent tachycardia, whereas embryos exposed to PbTx-1 displayed bradycardia, the onset of which was delayed. PMID:14644667

  18. Lactate adversely affects the in vitro formation of endothelial cell tubular structures through the action of TGF-{beta}1

    SciTech Connect

    Schmid, Stephan A. . E-mail: leoni.kunz-schughart@oncoray.de; Gaumann, Andreas; Wondrak, Marit; Eckermann, Christoph; Schulte, Stephanie; Mueller-Klieser, Wolfgang; Wheatley, Denys N.; Kunz-Schughart, Leoni A.

    2007-07-15

    When lactate accumulation in a tumor microenvironment reaches an average concentration of 10-20 mM, it tends to reflect a high degree of malignancy. However, the hypothesis that tumor-derived lactate has a number of partially adverse biological effects on malignant and tumor-associated host cells requires further evidence. The present study attempted to evaluate the impact of lactate on the process of angiogenesis, in particular on the formation of tubular structures. The endothelial cell (EC) network in desmoplastic breast tumors is primarily located in areas of reactive fibroblastic stroma. We employed a fibroblast-endothelial cell co-culture model as in vitro angiogenesis system normally producing florid in vitro tubule formation to analyze this situation. In contrast to previous studies, we found that lactate significantly reduces EC network formation in a dose-dependent manner as quantified by semi-automated morphometric analyses following immunohistochemical staining. The decrease in CD31-positive tubular structures and the number of intersections was independent of VEGF supplementation and became more pronounced in the presence of protons. The number of cells, primarily of the fibroblast population, was reduced but cell loss could not be attributed to a decrease in proliferative activity or pronounced apoptotic cell death. Treatment with 10 mM lactate was accompanied by enhanced mRNA expression and release of TGF-{beta}1, which also shows anti-angiogenic activity in the model. Both TGF-{beta}1 and lactate induced myofibroblastic differentiation adjacent to the EC tubular structures. The lactate response on the EC network was diminished by TGF-{beta}1 neutralization, indicating a causal relationship between lactate and TGF-{beta}1 in the finely tuned processes of vessel formation and maturation which may also occur in vivo within tumor tissue.

  19. A Computational Study on the Effects of Dynamic Roughness Application to Separated Transitional Flows Affected by Adverse Pressure Gradient

    NASA Astrophysics Data System (ADS)

    Campitelli, Gennaro

    The study of transitional flows is considered crucial for many practical engineering applications. In fact, a comprehensive understanding of the laminar-turbulent transition phenomenon often helps to improve the overall performance of apparatuses such as airfoils, wind turbines, hulls and turbomachinery blades. In addition to understanding and prediction of transitional flows, active research continues in the area of boundary layer control, which includes control of phenomena such as flow separation and transition. For instance, optimum geometrical shaping may be followed by the adoption on the wall-surface of riblets to adjust pressure gradient and reduce drag. Further "flow control" may also be acquired by introducing active devices able to modify the flow field in order to accomplish a desired aerodynamic task. Such flow manipulation is often achieved by using time-dependent forcing mechanisms which promote natural instabilities amplifying the control effectiveness. Localized energy inputs such as Lorentz-force actuator, piezoelectric flaps and synthetic jets all produce a consistent boundary layer mixing enhancement with lift increase and drag abatement. The current numerical study attempts to demonstrate the efficacy of dynamic roughness (DR) on altering separated-reattached transitional flows under adverse pressure gradient. It has already been proven how DR, acting on the boundary sublayer perturbation, is able to suppress (partially or completely) the typical leading edge separation for an airfoil at different angles of attack. This makes DR particularly suitable for separated flow control applications where the shear layer reattaches presenting the characteristic laminar separation bubble. A numerical sensitivity study has been conducted with an efficient orthogonal design taking into account four different control parameters on three levels (actuation frequency, humps height, rows displacement, synchronization) to provide an optimum DR setup which limits

  20. The skin tissue is adversely affected by TNF-alpha blockers in patients with chronic inflammatory arthritis: a 5-year prospective analysis

    PubMed Central

    Machado, Natalia P.; dos Reis Neto, Edgard Torres; Soares, Maria Roberta M. P.; Freitas, Daniele S.; Porro, Adriana; Ciconelli, Rozana M.; Pinheiro, Marcelo M.

    2013-01-01

    OBJECTIVE: We evaluated the incidence of and the main risk factors associated with cutaneous adverse events in patients with chronic inflammatory arthritis following anti-TNF-α therapy. METHODS: A total of 257 patients with active arthritis who were taking TNF-α blockers, including 158 patients with rheumatoid arthritis, 87 with ankylosing spondylitis and 12 with psoriatic arthritis, were enrolled in a 5-year prospective analysis. Patients with overlapping or other rheumatic diseases were excluded. Anthropometric, socioeconomic, demographic and clinical data were evaluated, including the Disease Activity Score-28, Bath Ankylosing Spondylitis Disease Activity Index and Psoriasis Area Severity Index. Skin conditions were evaluated by two dermatology experts, and in doubtful cases, skin lesion biopsies were performed. Associations between adverse cutaneous events and clinical, demographic and epidemiological variables were determined using the chi-square test, and logistic regression analyses were performed to identify risk factors. The significance level was set at p<0.05. RESULTS: After 60 months of follow-up, 71 adverse events (73.85/1000 patient-years) were observed, of which allergic and immune-mediated phenomena were the most frequent events, followed by infectious conditions involving bacterial (47.1%), parasitic (23.5%), fungal (20.6%) and viral (8.8%) agents. CONCLUSION: The skin is significantly affected by adverse reactions resulting from the use of TNF-α blockers, and the main risk factors for cutaneous events were advanced age, female sex, a diagnosis of rheumatoid arthritis, disease activity and the use of infliximab. PMID:24141833

  1. Metformin revisited: Does this regulator of AMP-activated protein kinase secondarily affect bone metabolism and prevent diabetic osteopathy

    PubMed Central

    McCarthy, Antonio Desmond; Cortizo, Ana María; Sedlinsky, Claudia

    2016-01-01

    Patients with long-term type 1 and type 2 diabetes mellitus (DM) can develop skeletal complications or “diabetic osteopathy”. These include osteopenia, osteoporosis and an increased incidence of low-stress fractures. In this context, it is important to evaluate whether current anti-diabetic treatments can secondarily affect bone metabolism. Adenosine monophosphate-activated protein kinase (AMPK) modulates multiple metabolic pathways and acts as a sensor of the cellular energy status; recent evidence suggests a critical role for AMPK in bone homeostasis. In addition, AMPK activation is believed to mediate most clinical effects of the insulin-sensitizer metformin. Over the past decade, several research groups have investigated the effects of metformin on bone, providing a considerable body of pre-clinical (in vitro, ex vivo and in vivo) as well as clinical evidence for an anabolic action of metformin on bone. However, two caveats should be kept in mind when considering metformin treatment for a patient with type 2 DM at risk for diabetic osteopathy. In the first place, metformin should probably not be considered an anti-osteoporotic drug; it is an insulin sensitizer with proven macrovascular benefits that can secondarily improve bone metabolism in the context of DM. Secondly, we are still awaiting the results of randomized placebo-controlled studies in humans that evaluate the effects of metformin on bone metabolism as a primary endpoint. PMID:27022443

  2. Metformin revisited: Does this regulator of AMP-activated protein kinase secondarily affect bone metabolism and prevent diabetic osteopathy.

    PubMed

    McCarthy, Antonio Desmond; Cortizo, Ana María; Sedlinsky, Claudia

    2016-03-25

    Patients with long-term type 1 and type 2 diabetes mellitus (DM) can develop skeletal complications or "diabetic osteopathy". These include osteopenia, osteoporosis and an increased incidence of low-stress fractures. In this context, it is important to evaluate whether current anti-diabetic treatments can secondarily affect bone metabolism. Adenosine monophosphate-activated protein kinase (AMPK) modulates multiple metabolic pathways and acts as a sensor of the cellular energy status; recent evidence suggests a critical role for AMPK in bone homeostasis. In addition, AMPK activation is believed to mediate most clinical effects of the insulin-sensitizer metformin. Over the past decade, several research groups have investigated the effects of metformin on bone, providing a considerable body of pre-clinical (in vitro, ex vivo and in vivo) as well as clinical evidence for an anabolic action of metformin on bone. However, two caveats should be kept in mind when considering metformin treatment for a patient with type 2 DM at risk for diabetic osteopathy. In the first place, metformin should probably not be considered an anti-osteoporotic drug; it is an insulin sensitizer with proven macrovascular benefits that can secondarily improve bone metabolism in the context of DM. Secondly, we are still awaiting the results of randomized placebo-controlled studies in humans that evaluate the effects of metformin on bone metabolism as a primary endpoint. PMID:27022443

  3. Factors that affect bone mineral accrual in the adolescent growth spurt.

    PubMed

    Whiting, Susan J; Vatanparast, Hassanali; Baxter-Jones, Adam; Faulkner, Robert A; Mirwald, Robert; Bailey, Donald A

    2004-03-01

    The development of bone mass during the growing years is an important determinant for risk of osteoporosis in later life. Adequate dietary intake during the growth period may be critical in reaching bone growth potential. The Saskatchewan Bone Mineral Accrual Study (BMAS) is a longitudinal study of bone growth in Caucasian children. We have calculated the times of maximal peak bone mineral content (BMC) velocity to be 14.0 +/- 1.0 y in boys and 12.5 +/- 0.9 y in girls; bone growth is maximal approximately 6 mo after peak height velocity. In the 2 y of peak skeletal growth, adolescents accumulate over 25% of adult bone. BMAS data may provide biological data on calcium requirements through application of calcium accrual values to factorial calculations of requirement. As well, our data are beginning to reveal how dietary patterns may influence attainment of bone mass during the adolescent growth spurt. Replacing milk intake by soft drinks appears to be detrimental to bone gain by girls, but not boys. Fruit and vegetable intake, providing alkalinity to bones and/or acting as a marker of a healthy diet, appears to influence BMC in adolescent girls, but not boys. The reason why these dietary factors appear to be more influential in girls than in boys may be that BMAS girls are consuming less than their requirement for calcium, while boys are above their threshold. Specific dietary and nutrient recommendations for adolescents are needed in order to ensure optimal bone growth and consolidation during this important life stage. PMID:14988470

  4. Paget's Disease of Bone

    MedlinePlus

    ... page please turn Javascript on. Paget's Disease of Bone What is Paget's Disease of Bone? Click for more information Enlarged and Misshapen Bones Paget's disease of bone causes affected bones to ...

  5. Subtle changes in bone mineralization density distribution in most severely affected patients with chronic obstructive pulmonary disease.

    PubMed

    Misof, B M; Roschger, P; Jorgetti, V; Klaushofer, K; Borba, V Z C; Boguszewski, C L; Cohen, A; Shane, E; Zhou, H; Dempster, D W; Moreira, C A

    2015-10-01

    Chronic obstructive pulmonary disease (COPD) is associated with low aBMD as measured by DXA and altered microstructure as assessed by bone histomorphometry and microcomputed tomography. Knowledge of bone matrix mineralization is lacking in COPD. Using quantitative backscatter electron imaging (qBEI), we assessed cancellous (Cn.) and cortical (Ct.) bone mineralization density distribution (BMDD) in 19 postmenopausal women (62.1 ± 7.3 years of age) with COPD. Eight had sustained fragility fractures, and 13 had received treatment with inhaled glucocorticoids. The BMDD outcomes from the patients were compared with healthy reference data and were correlated with previous clinical and histomorphometric findings. In general, the BMDD outcomes for the patients were not significantly different from the reference data. Neither the subgroups of with or without fragility fractures or of who did or did not receive inhaled glucocorticoid treatment, showed differences in BMDD. However, subgroup comparison according to severity revealed 10% decreased cancellous mineralization heterogeneity (Cn.CaWidth) for the most severely affected compared with less affected patients (p=0.042) and compared with healthy premenopausal controls (p=0.021). BMDD parameters were highly correlated with histomorphometric cancellous bone volume (BV/TV) and formation indices: mean degree of mineralization (Cn.CaMean) versus BV/TV (r=0.58, p=0.009), and Cn.CaMean and Ct.CaMean versus bone formation rate (BFR/BS) (r=-0.71, p<0.001). In particular, those with lower BV/TV (<50th percentile) had significantly lower Cn.CaMean (p=0.037) and higher Cn.CaLow (p=0.020) compared with those with higher (>50th percentile) BV/TV. The normality in most of the BMDD parameters and bone formation rates as well as the significant correlations between them suggests unaffected mineralization processes in COPD. Our findings also indicate no significant negative effect of treatment with inhaled glucocorticoids on the bone

  6. Task-Oriented and Bottle Feeding Adversely Affect the Quality of Mother-Infant Interactions Following Abnormal Newborn Screens

    PubMed Central

    Tluczek, Audrey; Clark, Roseanne; McKechnie, Anne Chevalier; Orland, Kate Murphy; Brown, Roger L.

    2010-01-01

    Objective Examine effects of newborn screening (NBS) and neonatal diagnosis on the quality of mother-infant interactions in the context of feeding. Methods Study compared the quality of mother-infant feeding interactions among four groups of infants classified by severity of NBS and diagnostic results: cystic fibrosis (CF), congenital hypothyroidism, heterozygote CF carrier, and healthy with normal NBS. The Parent-Child Early Relational Assessment and a task-oriented item measured the quality of feeding interactions for 130 dyads, infant ages 3–19 weeks (M=9.19, SD=3.28). The Center for Epidemiologic Studies Depression Scale and State-Trait Anxiety Inventory measured maternal depression and anxiety. Results Composite Indicator Structure Equation Modeling showed that infant diagnostic status and, to a lesser extent, maternal education predicted feeding method. Mothers of infants with CF were most likely to bottle feed, which was associated with more task-oriented maternal behavior than breastfeeding. Mothers with low task-oriented behavior showed more sensitivity and responsiveness to infant cues, as well as less negative affect and behavior in their interactions with their infants than mothers with high task-oriented scores. Mothers of infants with CF were significantly more likely to have clinically significant anxiety and depression than the other groups. However, maternal psychological profile did not predict feeding method or interaction quality. Conclusions Mothers in the CF group were the least likely to breastfeed. Research is needed to explicate long-term effects of feeding methods on quality of mother-child relationship and ways to promote continued breastfeeding following a neonatal CF diagnosis. PMID:20495477

  7. The negative bone effects of the disease and of chronic corticosteroid treatment in premenopausal women affected by rheumatoid arthritis.

    PubMed

    Fassio, A; Idolazzi, L; Jaber, M A; Dartizio, C; Viapiana, O; Rossini, M; Gatti, D

    2016-01-01

    Osteoporosis is a well-known extra-articular complication in rheumatoid arthritis (RA). The chronic corticosteroid treatment, the functional impairment associated with RA and the disease itself appear to be the most relevant determinants. Most of the previous studies involved postmenopausal women, in whom the estrogenic deficiency might amplify the negative effect towards bone of both RA and corticosteroid therapy. We decided to evaluate bone health in a cohort of premenopausal RA patients. The study population includes 47 premenopausal women attending our outpatient clinic for RA and twice as many healthy age-matched control women selected from the hospital personnel. The bone density at the spine and femoral neck were significantly lower in patients with RA as compared with controls. When spine bone mineral density (BMD) values were adjusted for the cumulative glucocorticoid (GC) dose alone and for the cumulative GC dose plus body mass index (BMI) the mean differences between two groups decreased but they remained statistically significant. We found no difference when the spine BMD was adjusted for cumulative GC dose, BMI and health assessment questionnaire. The difference in femoral neck BMD remained statistically significant also after all the same adjustments. In conclusion, our study shows that a BMD deficiency is frequent also in premenopausal women affected by RA, especially at femoral site and that the main determinants of this bone loss are not only the disease-related weight loss, corticosteroid therapy and functional impairment, but also the systemic effects of the disease itself. PMID:27608794

  8. Audiologic Patterns of Otic Capsule Preserving Temporal Bone Fracture: Effects of the Affected Subsites

    PubMed Central

    Kim, So Young; Kim, Yoon Joong; Kim, Young Ho; Park, Min-Hyun

    2016-01-01

    Objectives. This study was aimed to assess the relationship between the type of temporal bone area involved and conductive hearing loss. Methods. We enrolled 97 patients who visited the otolaryngology clinics of Seoul National University Hospital or Boramae Medical Center, Seoul Metropolitan Government-Seoul National University with temporal bone fracture between January 2004 and January 2014. Audiometric parameters, including initial and improved air-bone (AB) conduction gap values, were reviewed in accordance with the temporal bone computed tomography (external auditory canal [EAC], middle ear [ME], mastoid [M], and ossicle [O]). Results. Patients with ossicular chain involvement exhibited a larger AB gap compared to those with no ossicular chain involvement at 250, 1,000, 2,000, and 4,000 Hz. Among the groups without ossicular chain involvement, the initial AB gap was largest in patients with EAC+ME+M involvement, followed by the ME+M and M-only involvement groups. The greatest improvement in the AB gap was observed in the EAC+ME+M group followed by the ME+M and M-only groups, irrespective of ossicular chain involvement. Improvements in AB gap values were smallest at 2,000 Hz. Conclusion. Conductive hearing loss pattern differed according to the temporal bone area involved. Therefore, areas such as the hematoma and hemotympanum, as well as the fracture line of the temporal bone area, must be evaluated to predict audiologic patterns with otic capsule preserving temporal bone fracture. PMID:27337953

  9. Markers of Bone Metabolism Are Affected by Renal Function and Growth Hormone Therapy in Children with Chronic Kidney Disease

    PubMed Central

    Doyon, Anke; Fischer, Dagmar-Christiane; Bayazit, Aysun Karabay; Canpolat, Nur; Duzova, Ali; Sözeri, Betül; Bacchetta, Justine; Balat, Ayse; Büscher, Anja; Candan, Cengiz; Cakar, Nilgun; Donmez, Osman; Dusek, Jiri; Heckel, Martina; Klaus, Günter; Mir, Sevgi; Özcelik, Gül; Sever, Lale; Shroff, Rukshana; Vidal, Enrico; Wühl, Elke; Gondan, Matthias; Melk, Anette; Querfeld, Uwe; Haffner, Dieter; Schaefer, Franz

    2015-01-01

    Objectives The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort. Methods Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6–18 years with an estimated glomerular filtration rate (eGFR) of 10–60 ml/min/1.73m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group. Results Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score. Conclusion Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity. PMID:25659076

  10. Bone quality is affected by food restriction and by nutrition-induced catch-up growth.

    PubMed

    Pando, Rakefet; Masarwi, Majdi; Shtaif, Biana; Idelevich, Anna; Monsonego-Ornan, Efrat; Shahar, Ron; Phillip, Moshe; Gat-Yablonski, Galia

    2014-12-01

    Growth stunting constitutes the most common effect of malnutrition. When the primary cause of malnutrition is resolved, catch-up (CU) growth usually occurs. In this study, we have explored the effect of food restriction (RES) and refeeding on bone structure and mechanical properties. Sprague-Dawley male rats aged 24 days were subjected to 10 days of 40% RES, followed by refeeding for 1 (CU) or 26 days long-term CU (LTCU). The rats fed ad libitum served as controls. The growth plates were measured, osteoclasts were identified using tartrate-resistant acid phosphatase staining, and micro-computed tomography (CT) scanning and mechanical testing were used to study structure and mechanical properties. Micro-CT analysis showed that RES led to a significant reduction in trabecular BV/TV and trabecular number (Tb.N), concomitant with an increase in trabecular separation (Tb.Sp). Trabecular BV/TV and Tb.N were significantly greater in the CU group than in the RES in both short- and long-term experiments. Mechanical testing showed that RES led to weaker and less compliant bones; interestingly, bones of the CU group were also more fragile after 1 day of CU. Longer term of refeeding enabled correction of the bone parameters; however, LTCU did not achieve full recovery. These results suggest that RES in young rats attenuated growth and reduced trabecular bone parameters. While nutrition-induced CU growth led to an immediate increase in epiphyseal growth plate height and active bone modeling, it was also associated with a transient reduction in bone quality. This should be taken into consideration when treating children undergoing CU growth. PMID:25248555

  11. Frequency of Teriparatide Administration Affects the Histological Pattern of Bone Formation in Young Adult Male Mice.

    PubMed

    Yamamoto, Tomomaya; Hasegawa, Tomoka; Sasaki, Muneteru; Hongo, Hiromi; Tsuboi, Kanako; Shimizu, Tomohiro; Ota, Masahiro; Haraguchi, Mai; Takahata, Masahiko; Oda, Kimimitsu; Luiz de Freitas, Paulo Henrique; Takakura, Aya; Takao-Kawabata, Ryoko; Isogai, Yukihiro; Amizuka, Norio

    2016-07-01

    Evidence supports that daily and once-weekly administration of teriparatide, human (h)PTH(1-34), enhance bone mass in osteoporotic patients. However, it is uncertain whether different frequencies of hPTH(1-34) administration would induce bone formation similarly in terms of quantity and quality. To investigate that issue, mice were subjected to different frequencies of PTH administration, and their bones were histologically examined. Frequencies of administration were 1 time/2 days, 1 time a day, and 2 and 4 times a day. Mice were allocated to either to control or to 3 different dosing regimens: 80 μg/kg of hPTH(1-34) per injection (80 μg/kg per dose), 80 μg/kg of hPTH(1-34) per day (80 μg/kg · d), or 20 μg/kg of hPTH(1-34) per day (20 μg/kg · d). With the regimens of 80 μg/kg per dose and 80 μg/kg · d, high-frequency hPTH(1-34) administration increased metaphyseal trabecular number. However, 4 doses per day induced the formation of thin trabeculae, whereas the daily PTH regimen resulted in thicker trabeculae. A similar pattern was observed with the lower daily hPTH(1-34) dose (20 μg/kg · d): more frequent PTH administration led to the formation of thin trabeculae, showing a thick preosteoblastic cell layer, several osteoclasts, and scalloped cement lines that indicated accelerated bone remodeling. On the other hand, low-frequency PTH administration induced new bone with mature osteoblasts lying on mildly convex surfaces representative of arrest lines, which suggests minimodeling-based bone formation. Thus, high-frequency PTH administration seems to increase bone mass rapidly by forming thin trabeculae through accelerated bone remodeling. Alternatively, low-frequency PTH administration leads to the formation of thicker trabeculae through bone remodeling and minimodeling. PMID:27227535

  12. Hoof position during limb loading affects dorsoproximal bone strains on the equine proximal phalanx.

    PubMed

    Singer, Ellen; Garcia, Tanya; Stover, Susan

    2015-07-16

    Sagittal fractures of the proximal phalanx (P1) in the racehorse appear to be associated with turf racing surfaces, which are known to restrict forward slide of the foot at impact. We hypothesized that restriction of forward foot slip would result in higher P1 bone strains during metacarpophalangeal joint (MCPJ) hyperextension. Unilateral limbs from six equine cadavers were instrumented with strain gauges and bone reference markers to measure dorsoproximal P1 bone strains and MCPJ extension, collateromotion and axial rotation during in vitro limb loading to 10,500 N. By limiting movement of the distal actuator platform, three different foot conditions (forward, free, and restricted) were applied in a randomised block design. Bone reference markers, recorded by video, were analyzed to determine motion of P1 relative to MC3. Rosette strain data were reduced to principal and shear magnitudes and directions. A mixed model ANOVA determined the effect of foot position on P1 bone strains and MCPJ angles. At 10,000 N load, the restricted condition resulted in higher P1 axial compressive (p=0.015), maximum shear (p=0.043) and engineering shear (p=0.046) strains compared to the forward condition. The restricted condition had higher compressive (p=0.025) and lower tensile (p=0.043) principal strains compared to the free condition. For the same magnitude of principal or shear strains, axial rotation and collateromotion angles were greatest for the restricted condition. Therefore, the increase in P1 principal compressive and shear bone strains associated with restricted foot slip indicate that alterations in foot:ground interaction may play a role in fracture occurrence in horses. PMID:26003484

  13. The behavior of the micro-mechanical cement-bone interface affects the cement failure in total hip replacement

    PubMed Central

    Waanders, Daan; Janssen, Dennis; Mann, Kenneth A.; Verdonschot, Nico

    2010-01-01

    In the current study, the effects of different ways to implement the complex micro-mechanical behavior of the cement-bone interface on the fatigue failure of the cement mantle was investigated. In an FEA-model of a cemented hip reconstruction the cement-bone interface was modeled and numerically implemented in four different ways: (I) as infinitely stiff, (II) as infinitely strong with a constant stiffness, (III) a mixed-mode failure response with failure in tension and shear, and (IV) realistic mixed mode behavior obtained from micro FEA-models. Case II, III and IV were analyzed using data from a stiff and a compliant micro-FEA model and their effects on cement failure were analyzed. The data used for Case IV was derived from experimental specimens that were tested previously. Although the total number of cement cracks was low for all cases, the compliant Case II resulted in twice as many cracks as Case I. All cases caused similar stress distributions at the interface. In all cases, the interface did not display interfacial softening; all stayed the elastic zone. Fatigue failure of the cement mantle resulted in a more favorable stress distribution at the cement-bone interface in terms of less tension and lower shear tractions. We conclude that immediate cement-bone interface failure is not likely to occur, but its local compliancy does affect the formation of cement cracks. This means that at a macro-level the cement-bone interface should be modeled as a compliant layer. However, implementation of interfacial post-yield softening does seem to be necessary. PMID:21036358

  14. Rye Affects Bacterial Translocation, Intestinal Viscosity, Microbiota Composition and Bone Mineralization in Turkey Poults

    PubMed Central

    Tellez, Guillermo; Latorre, Juan D.; Kuttappan, Vivek A.; Hargis, Billy M.; Hernandez-Velasco, Xochitl

    2015-01-01

    Previously, we have reported that rye significantly increased both viscosity and Clostridium perfringens proliferation when compared with corn in an in vitro digestive model. Two independent trials were conducted to evaluate the effect of rye as a source of energy on bacterial translocation, intestinal viscosity, gut microbiota composition, and bone mineralization, when compared with corn in turkey poults. In each experiment, day-of-hatch, turkey poults were randomly assigned to either a corn or a rye diet (n = 0 /group). At 10 d of age, in both experiments, 12 birds/group were given an oral gavage dose of fluorescein isothiocyanate dextran (FITC-d). After 2.5 h of oral gavage, blood and liver samples were collected to evaluate the passage of FITC-d and bacterial translocation (BT) respectively. Duodenum, ileum and cecum gut sections were collected to evaluate intestinal viscosity and to enumerate gut microbiota. Tibias were collected for observation of bone parameters. Broilers fed with a rye diet showed increased (p<0.05) intestinal viscosity, BT, and serum FITC-d. Bacterial enumeration revealed that turkey poults fed with rye had increased the number of total lactic acid bacteria (LAB) in all three sections of the gastrointestinal tract evaluated when compared to turkey poults fed with corn. Turkey poults fed with rye also had significantly higher coliforms in duodenum and ileum but not in the ceca, whereas the total number of anaerobes increased only in duodenum. A significant reduction in bone strength and bone mineralization was observed in turkey poults fed with rye when compared with corn fed turkey poults. In conclusion, rye evoked mucosal damage in turkey poults that increased intestinal viscosity, increased leakage through the intestinal tract, and altered the microbiota composition and bone mineralization. Studies to evaluate dietary inclusion of selected Direct-Fed Microbial (DFM) candidates that produce exogenous enzymes in rye fed turkey poults are

  15. Rye affects bacterial translocation, intestinal viscosity, microbiota composition and bone mineralization in Turkey poults.

    PubMed

    Tellez, Guillermo; Latorre, Juan D; Kuttappan, Vivek A; Hargis, Billy M; Hernandez-Velasco, Xochitl

    2015-01-01

    Previously, we have reported that rye significantly increased both viscosity and Clostridium perfringens proliferation when compared with corn in an in vitro digestive model. Two independent trials were conducted to evaluate the effect of rye as a source of energy on bacterial translocation, intestinal viscosity, gut microbiota composition, and bone mineralization, when compared with corn in turkey poults. In each experiment, day-of-hatch, turkey poults were randomly assigned to either a corn or a rye diet (n = 0 /group). At 10 d of age, in both experiments, 12 birds/group were given an oral gavage dose of fluorescein isothiocyanate dextran (FITC-d). After 2.5 h of oral gavage, blood and liver samples were collected to evaluate the passage of FITC-d and bacterial translocation (BT) respectively. Duodenum, ileum and cecum gut sections were collected to evaluate intestinal viscosity and to enumerate gut microbiota. Tibias were collected for observation of bone parameters. Broilers fed with a rye diet showed increased (p<0.05) intestinal viscosity, BT, and serum FITC-d. Bacterial enumeration revealed that turkey poults fed with rye had increased the number of total lactic acid bacteria (LAB) in all three sections of the gastrointestinal tract evaluated when compared to turkey poults fed with corn. Turkey poults fed with rye also had significantly higher coliforms in duodenum and ileum but not in the ceca, whereas the total number of anaerobes increased only in duodenum. A significant reduction in bone strength and bone mineralization was observed in turkey poults fed with rye when compared with corn fed turkey poults. In conclusion, rye evoked mucosal damage in turkey poults that increased intestinal viscosity, increased leakage through the intestinal tract, and altered the microbiota composition and bone mineralization. Studies to evaluate dietary inclusion of selected Direct-Fed Microbial (DFM) candidates that produce exogenous enzymes in rye fed turkey poults are

  16. Genetically-induced Estrogen Receptor Alpha mRNA (Esr1) Overexpression Does Not Adversely Affect Fertility or Penile Development in Male Mice

    PubMed Central

    Heath, John; Abdelmageed, Yazeed; Braden, Tim D.; Williams, Carol S.; Williams, John W.; Paulose, Tessie; Hernandez-Ochoa, Isabel; Gupta, Rupesh; Flaws, Jodi A.; Goyal, Hari O.

    2011-01-01

    Previously, we reported that estrogen receptor alpha mRNA (Esr1) or protein (ESR1) overexpression resulting from neonatal exposure to estrogens in rats was associated with infertility and mal-developed penis characterized by reduced length and weight and abnormal accumulation of fat cells. The objective of this study was to determine if mutant male mice overexpressing Esr1 are naturally infertile or have reduced fertility and/or develop abnormal penis. The fertility parameters, including fertility and fecundity indices, numbers of days from the day of cohabitation to the day of delivery, and numbers of pups per female, were not altered from controls, as a result of Esr1 overexpression. Likewise, penile morphology, including the length, weight, and diameter and os penis development, was not altered from controls. Conversely, weights of the seminal vesicles and bulbospongiosus and levator ani (BS/LA) muscles were significantly (P < 0.05) lower as compared to controls; however, the weight of the testis, the morphology of the testis and epididymis, and the plasma and testicular testosterone concentration were not different from controls. Hence, the genetically-induced Esr1 overexpression alone, without an exogenous estrogen exposure during the neonatal period, is unable to adversely affect the development of the penis as well as other male reproductive organs, except limited, but significant, reductions in weights of the seminal vesicles and BS/LA muscles. PMID:20930192

  17. Interindividual anatomical variations affect the plate-to-bone fit during osteosynthesis of distal radius fractures.

    PubMed

    Yoneda, Hidemasa; Iwatsuki, Katsuyuki; Hara, Tatsuya; Kurimoto, Shigeru; Yamamoto, Michiro; Hirata, Hitoshi

    2016-06-01

    We hypothesized that interindividual variations in the teardrop, which represents the volar projection of the lunate facet of the distal radius, cause unsatisfactory fitting of the volar locking plate to the bone. This can cause flexor tendon ruptures. Herein, we conducted a cross-sectional study and measured the ratio of teardrop height and the teardrop inclination angle as parameters of teardrop configuration for 200 standardized lateral radiographs (average age of the patients, 51 years). We also quantified the influence of the teardrop morphology by analyzing the fit of three locking plates to three radii with differing teardrop inclination angles using a three-dimensional computer-aided design system. The average ratios of the teardrop height and teardrop inclination angle were 0.42° (0.30-0.56°) and 28.8° (9.9-44.9°), respectively. The teardrop inclination angle was moderately correlated with age in men but not in women. In the plate-to-bone fit analyses, the fit of all the plates was significantly different between bones, with the configuration of the radius with the lowest teardrop inclination angle being the closest approximation to that of each plate. We demonstrated the interindividual variation in the shape of the teardrop and its influence on the fit of the volar plate, highlighting the importance of careful plate selection for achieving osteosynthesis of bones with a high teardrop inclination angle. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:953-960, 2016. PMID:26648456

  18. Do Nonsteroidal Anti-Inflammatory Drugs Affect Bone Healing? A Critical Analysis

    PubMed Central

    Pountos, Ippokratis; Georgouli, Theodora; Calori, Giorgio M.; Giannoudis, Peter V.

    2012-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) play an essential part in our approach to control pain in the posttraumatic setting. Over the last decades, several studies suggested that NSAIDs interfere with bone healing while others contradict these findings. Although their analgesic potency is well proven, clinicians remain puzzled over the potential safety issues. We have systematically reviewed the available literature, analyzing and presenting the available in vitro animal and clinical studies on this field. Our comprehensive review reveals the great diversity of the presented data in all groups of studies. Animal and in vitro studies present so conflicting data that even studies with identical parameters have opposing results. Basic science research defining the exact mechanism with which NSAIDs could interfere with bone cells and also the conduction of well-randomized prospective clinical trials are warranted. In the absence of robust clinical or scientific evidence, clinicians should treat NSAIDs as a risk factor for bone healing impairment, and their administration should be avoided in high-risk patients. PMID:22272177

  19. Do nonsteroidal anti-inflammatory drugs affect bone healing? A critical analysis.

    PubMed

    Pountos, Ippokratis; Georgouli, Theodora; Calori, Giorgio M; Giannoudis, Peter V

    2012-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) play an essential part in our approach to control pain in the posttraumatic setting. Over the last decades, several studies suggested that NSAIDs interfere with bone healing while others contradict these findings. Although their analgesic potency is well proven, clinicians remain puzzled over the potential safety issues. We have systematically reviewed the available literature, analyzing and presenting the available in vitro animal and clinical studies on this field. Our comprehensive review reveals the great diversity of the presented data in all groups of studies. Animal and in vitro studies present so conflicting data that even studies with identical parameters have opposing results. Basic science research defining the exact mechanism with which NSAIDs could interfere with bone cells and also the conduction of well-randomized prospective clinical trials are warranted. In the absence of robust clinical or scientific evidence, clinicians should treat NSAIDs as a risk factor for bone healing impairment, and their administration should be avoided in high-risk patients. PMID:22272177

  20. Bone tumor

    MedlinePlus

    ... physical exam. Tests that may be done include: Alkaline phosphatase blood level Bone biopsy Bone scan Chest x- ... also affect the results of the following tests: Alkaline phosphatase isoenzyme Blood calcium level Parathyroid hormone Blood phosphorus ...

  1. Factors that affect postnatal bone growth retardation in the twitcher murine model of Krabbe disease

    PubMed Central

    Contreras, Miguel Agustin; Ries, William Louis; Shanmugarajan, Srinivasan; Arboleda, Gonzalo; Singh, Inderjit; Singh, Avtar Kaur

    2010-01-01

    Krabbe disease is an inherited lysosomal disorder in which galactosylsphingosine (psychosine) accumulates mainly in the central nervous system. To gain insight into the possible mechanism(s) that may be participating in the inhibition of the postnatal somatic growth described in the animal model of this disease (twitcher mouse, twi), we studied their femora. This study reports that twi femora are smaller than of those of wild type (wt), and present with abnormality of marrow cellularity, bone deposition (osteoblastic function), and osteoclastic activity. Furthermore, lipidomic analysis indicates altered sphingolipid homeostasis, but without significant changes in the levels of sphingolipid-derived intermediates of cell death (ceramide) or the levels of the osteoclast-osteoblast coupling factor (sphingosine-1-phosphate). However, there was significant accumulation of psychosine in the femora of adult twi animals as compared to wt, without induction of tumor necrosis factor-alpha or interleukin-6. Analysis of insulin-like growth factor-1 (IGF-1) plasma levels, a liver secreted hormone known to play a role in bone growth, indicated a drastic reduction in twi animals when compared to wt. To identify the cause of the decrease, we examined the IGF-1 mRNA expression and protein levels in the liver. The results indicated a significant reduction of IGF-1 mRNA as well as protein levels in the liver from twi as compared to wt littermates. Our data suggest that a combination of endogenous (psychosine) and endocrine (IGF-1) factors play a role in the inhibition of postnatal bone growth in twi mice; and further suggest that derangements of liver function may be contributing, at least in part, to this alteration. PMID:20441793

  2. Age and skeletal sites affect BMP-2 responsiveness of human bone marrow stromal cells.

    PubMed

    Osyczka, Anna Maria; Damek-Poprawa, Monika; Wojtowicz, Aleksandra; Akintoye, Sunday O

    2009-01-01

    Bone marrow stromal cells (BMSCs) contain osteoprogenitors responsive to stimulation by osteogenic growth factors like bone morphogenetic proteins (BMPs). When used as grafts, BMSCs can be harvested from different skeletal sites such as axial, appendicular, and orofacial bones, but the lower therapeutic efficacy of BMPs on BMSCs-responsiveness in humans compared to animal models may be due partly to effects of skeletal site and age of donor. We previously reported superior differentiation capacity and osteogenic properties of orofacial BMSCs relative to iliac crest BMSCs in same individuals. This study tested the hypothesis that recombinant human BMP-2 (rhBMP-2) stimulates human BMSCs differently based on age and skeletal site of harvest. Adult maxilla, mandible, and iliac crest BMSCs from same individuals and pediatric iliac crest BMSCs were comparatively assessed for BMP-2 responsiveness under serum-containing and serum-free insulin-supplemented culture conditions. Adult orofacial BMSCs were more BMP-2-responsive than iliac crest BMSCs based on higher gene transcripts of alkaline phosphatase, osteopontin, and osteogenic transcription factors MSX-2 and Osterix in serum-free insulin-containing medium. Pediatric iliac crest BMSCs were more responsive to rhBMP-2 than adult iliac crest BMSCs based on higher expression of alkaline phosphatase and osteopontin in serum-containing medium. Unlike orofacial BMSCs, MSX-2 and Osterix transcripts were similarly expressed by adult and pediatric iliac crest BMSCs in response to rhBMP-2. These data demonstrate that age and skeletal site-specific differences exist in BMSC osteogenic responsiveness to BMP-2 stimulation and suggest that MSX-2 and Osterix may be potential regulatory transcription factors in BMP-mediated osteogenesis of adult orofacial cells. PMID:19637063

  3. Age and Skeletal Sites Affect BMP-2 Responsiveness of Human Bone Marrow Stromal Cells

    PubMed Central

    Osyczka, Anna M.; Damek-Poprawa, Monika; Wojtowicz, Aleksandra; Akintoye, Sunday O.

    2010-01-01

    Bone marrow stromal cells (BMSCs) contain osteoprogenitors responsive to stimulation by osteogenic growth factors like bone morphogenetic proteins (BMPs). When used as grafts, BMSCs can be harvested from different skeletal sites such as axial, appendicular and orofacial bones, but the lower therapeutic efficacy of BMPs on BMSCs-responsiveness in humans compared to animal models may be partly due to effects of skeletal site and age of donor. We previously reported superior differentiation capacity and osteogenic properties of orofacial BMSCs relative to iliac crest BMSCs in same individuals. This study tested the hypothesis that recombinant human BMP-2 (rhBMP-2) stimulates human BMSCs differently based on age and skeletal site of harvest. Adult maxilla, mandible and iliac crest BMSCs from same individuals and pediatric iliac crest BMSCs were comparatively assessed for BMP-2 responsiveness under serum-containing and serum-free insulin-supplemented culture conditions. Adult orofacial BMSCs were more BMP-2-responsive than iliac crest BMSCs based on higher gene transcripts of alkaline phosphatase, osteopontin and osteogenic transcription factors MSX-2 and Osterix in serum-free insulin-containing medium. Pediatric iliac crest BMSCs were more responsive to rhBMP-2 than adult iliac crest BMSCs based on higher expression of alkaline phosphatase and osteopontin in serum-containing medium. Unlike orofacial BMSCs, MSX-2 and Osterix transcripts were similarly expressed by adult and pediatric iliac crest BMSCs in response to rhBMP-2. These data demonstrate that age and skeletal site-specific differences exist in BMSC osteogenic responsiveness to BMP-2 stimulation and suggest that MSX-2 and Osterix may be potential regulatory transcription factors in BMP-mediated osteogenesis of adult orofacial cells. PMID:19637063

  4. Integrating Epigenomic Elements and GWASs Identifies BDNF Gene Affecting Bone Mineral Density and Osteoporotic Fracture Risk

    PubMed Central

    Guo, Yan; Dong, Shan-Shan; Chen, Xiao-Feng; Jing, Ying-Aisha; Yang, Man; Yan, Han; Shen, Hui; Chen, Xiang-Ding; Tan, Li-Jun; Tian, Qing; Deng, Hong-Wen; Yang, Tie-Lin

    2016-01-01

    To identify susceptibility genes for osteoporosis, we conducted an integrative analysis that combined epigenomic elements and previous genome-wide association studies (GWASs) data, followed by validation at population and functional levels, which could identify common regulatory elements and predict new susceptibility genes that are biologically meaningful to osteoporosis. By this approach, we found a set of distinct epigenomic elements significantly enriched or depleted in the promoters of osteoporosis-associated genes, including 4 transcription factor binding sites, 27 histone marks, and 21 chromatin states segmentation types. Using these epigenomic marks, we performed reverse prediction analysis to prioritize the discovery of new candidate genes. Functional enrichment analysis of all the prioritized genes revealed several key osteoporosis related pathways, including Wnt signaling. Genes with high priority were further subjected to validation using available GWASs datasets. Three genes were significantly associated with spine bone mineral density, including BDNF, PDE4D, and SATB2, which all closely related to bone metabolism. The most significant gene BDNF was also associated with osteoporotic fractures. RNA interference revealed that BDNF knockdown can suppress osteoblast differentiation. Our results demonstrated that epigenomic data could be used to indicate common epigenomic marks to discover additional loci with biological functions for osteoporosis. PMID:27465306

  5. Integrating Epigenomic Elements and GWASs Identifies BDNF Gene Affecting Bone Mineral Density and Osteoporotic Fracture Risk.

    PubMed

    Guo, Yan; Dong, Shan-Shan; Chen, Xiao-Feng; Jing, Ying-Aisha; Yang, Man; Yan, Han; Shen, Hui; Chen, Xiang-Ding; Tan, Li-Jun; Tian, Qing; Deng, Hong-Wen; Yang, Tie-Lin

    2016-01-01

    To identify susceptibility genes for osteoporosis, we conducted an integrative analysis that combined epigenomic elements and previous genome-wide association studies (GWASs) data, followed by validation at population and functional levels, which could identify common regulatory elements and predict new susceptibility genes that are biologically meaningful to osteoporosis. By this approach, we found a set of distinct epigenomic elements significantly enriched or depleted in the promoters of osteoporosis-associated genes, including 4 transcription factor binding sites, 27 histone marks, and 21 chromatin states segmentation types. Using these epigenomic marks, we performed reverse prediction analysis to prioritize the discovery of new candidate genes. Functional enrichment analysis of all the prioritized genes revealed several key osteoporosis related pathways, including Wnt signaling. Genes with high priority were further subjected to validation using available GWASs datasets. Three genes were significantly associated with spine bone mineral density, including BDNF, PDE4D, and SATB2, which all closely related to bone metabolism. The most significant gene BDNF was also associated with osteoporotic fractures. RNA interference revealed that BDNF knockdown can suppress osteoblast differentiation. Our results demonstrated that epigenomic data could be used to indicate common epigenomic marks to discover additional loci with biological functions for osteoporosis. PMID:27465306

  6. Obstructive sleep apnea and metabolic bone disease: Insights in to the relationship between bone and sleep

    PubMed Central

    Swanson, Christine M.; Shea, Steven A.; Stone, Katie L.; Cauley, Jane A.; Rosen, Clifford J.; Redline, Susan; Karsenty, Gerard; Orwoll, Eric S.

    2015-01-01

    Obstructive sleep apnea (OSA) and low bone mass are two prevalent conditions, particularly among older adults, a section of the U.S. population that is expected to grow dramatically over the coming years. OSA, the most common form of sleep disordered breathing, has been linked to multiple cardiovascular, metabolic, hormonal and inflammatory derangements and may have adverse effects on bone. However, little is known about how OSA (including the associated hypoxia and sleep loss) affects bone metabolism. In order to gain insight into the relationship between sleep and bone, we review the growing information on OSA and metabolic bone disease and discuss the pathophysiological mechanisms by which OSA may affect bone metabolism/architecture. PMID:25639209

  7. Effect of Nasal Calcitonin on the Health-Related Quality of Life in Postmenopause Women Affected With Low Bone Density

    PubMed Central

    Shohrati, Majid; Bayat, Noushin; Saburi, Amin; Abbasi, Zahra

    2015-01-01

    Background: Physical activity and mental health could be affected by osteoporosis and various therapeutic options such as calcitonin may influence Quality Of Life (QOL) of these patients with Low Bone Density (LBD). Objectives: This study aimed to evaluate the effect of nasal calcitonin on QOL in post menopause women with LBD. Patients and Methods: This clinical trial study was performed on one hundred and fifteen menopause women with LBD less than 1 SD in Bone Mineral Densitometry (BMD) referred to Baqiyatallah Hospital in Tehran, Iran, during 2009 - 2010. They were assigned to receive 200 IU calcitonin nasal spray along with calcium (1000 mg) and vitamin D (400 IU) for 6 months. Quality of life was assessed by Short-Form 36 (SF-36) questionnaire (Persian-validated version). Results: The mean age (± SD) of the participants was 58.75 ± 8.15 years. Intranasal spray of calcitonin increased QOL scores significantly (88.05 ± 15.63 vs. 92.15 ± 13.22, P value = 0.000). Bone mineral density of spine was increased from 0.834 ± 0.11 to 0.12 ± 0.852 and this difference in BMD of lumbar spine was statistically significant (P value: 0.003) but not significant in femur’s BMD (P value = 0.061). In comparison with BMD indexes, The QOL scores especially Mental Health domain changes had only a significant correlation with the changes of total T score in BMD (P = 0.031, Coefficient Correlation = 0.248). Conclusions: It seems that nasal spray of calcitonin can effectively improve QOL of women with LBD and QOL changes were not influenced by clinical or para-clinical alteration. Mental health domain must be more considered in further studies as a predicting domain for Health-Related Quality of Life (HR-QOL) changes. PMID:26421180

  8. Carpal Tunnel Cross-Sectional Area Affected by Soft Tissues Abutting the Carpal Bones.

    PubMed

    Gabra, Joseph N; Li, Zong-Ming

    2013-02-01

    The carpal tunnel accommodates free movement of its contents, and the tunnel's cross-sectional area is a useful morphological parameter for the evaluation of the space available for the carpal tunnel contents and of potential nerve compression in the tunnel. The osseous boundary of the carpal bones as the dorsal border of the carpal tunnel is commonly used to determine the tunnel area, but this boundary contains soft tissues such as numerous intercarpal ligaments and the flexor carpi radialis tendon. The aims of this study were to quantify the thickness of the soft tissues abutting the carpal bones and to investigate how this soft tissue influences the calculation of the carpal tunnel area. Magnetic resonance images were analyzed for eight cadaveric specimens. A medical balloon with a physiological pressure was inserted into an evacuated tunnel to identify the carpal tunnel boundary. The balloon-based (i.e. true carpal tunnel) and osseous-based carpal tunnel boundaries were extracted and divided into regions corresponding to the hamate, capitate, trapezoid, trapezium, and transverse carpal ligament (TCL). From the two boundaries, the overall and regional soft tissue thicknesses and areas were calculated. The soft tissue thickness was significantly greater for the trapezoid (3.1±1.2mm) and trapezium (3.4±1.0mm) regions than for the hamate (0.7±0.3mm) and capitate (1.2±0.5mm) regions. The carpal tunnel area using the osseous boundary (243.0±40.4mm(2)) was significantly larger than the balloon-based area (183.9±29.7mm(2)) with a ratio of 1.32. In other words, the carpal tunnel area can be estimated as 76% (= 1/1.32) of the osseous-based area. The abundance of soft tissue in the trapezoid and trapezium regions can be attributed mainly to the capitate-trapezium ligament and the flexor carpi radialis tendon. Inclusion of such soft tissue leads to overestimations of the carpal tunnel area. Correct quantification of the carpal tunnel area aids in examining carpal

  9. Carpal Tunnel Cross-Sectional Area Affected by Soft Tissues Abutting the Carpal Bones

    PubMed Central

    Gabra, Joseph N.; Li, Zong-Ming

    2013-01-01

    The carpal tunnel accommodates free movement of its contents, and the tunnel's cross-sectional area is a useful morphological parameter for the evaluation of the space available for the carpal tunnel contents and of potential nerve compression in the tunnel. The osseous boundary of the carpal bones at the dorsal border of the carpal tunnel is commonly used to determine the tunnel area, but this boundary contains soft tissues such as numerous intercarpal ligaments and the flexor carpi radialis tendon. The aims of this study were to quantify the thickness of the soft tissues abutting the carpal bones and to investigate how this soft tissue influences the calculation of the carpal tunnel area. Magnetic resonance images were analyzed for eight cadaveric specimens. A medical balloon with a physiological pressure was inserted into an evacuated tunnel to identify the carpal tunnel boundary. The balloon-based (i.e., true carpal tunnel) and osseous-based carpal tunnel boundaries were extracted and divided into regions corresponding to the hamate, capitate, trapezoid, trapezium, and transverse carpal ligament (TCL). From the two boundaries, the overall and regional soft tissue thicknesses and areas were calculated. The soft tissue thickness was significantly greater for the trapezoid (3.1 ± 1.2 mm) and trapezium (3.4 ± 1.0 mm) regions than for the hamate (0.7 ± 0.3 mm) and capitate (1.2 ± 0.5 mm) regions. The carpal tunnel area using the osseous boundary (243.0 ± 40.4 mm2) was significantly larger than the balloon-based area (183.9 ± 29.7 mm2) with a ratio of 1.32. In other words, the carpal tunnel area can be estimated as 76% (= 1/1.32) of the osseous-based area. The abundance of soft tissue in the trapezoid and trapezium regions can be attributed mainly to the capitotrapezial ligament and the flexor carpi radialis tendon. Inclusion of such soft tissue leads to overestimations of the carpal tunnel area. Correct quantification of the carpal

  10. The rice FISH BONE gene encodes a tryptophan aminotransferase, which affects pleiotropic auxin-related processes.

    PubMed

    Yoshikawa, Takanori; Ito, Momoyo; Sumikura, Tsuyoshi; Nakayama, Akira; Nishimura, Takeshi; Kitano, Hidemi; Yamaguchi, Isomaro; Koshiba, Tomokazu; Hibara, Ken-Ichiro; Nagato, Yasuo; Itoh, Jun-Ichi

    2014-06-01

    Auxin is a fundamental plant hormone and its localization within organs plays pivotal roles in plant growth and development. Analysis of many Arabidopsis mutants that were defective in auxin biosynthesis revealed that the indole-3-pyruvic acid (IPA) pathway, catalyzed by the TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS (TAA) and YUCCA (YUC) families, is the major biosynthetic pathway of indole-3-acetic acid (IAA). In contrast, little information is known about the molecular mechanisms of auxin biosynthesis in rice. In this study, we identified a auxin-related rice mutant, fish bone (fib). FIB encodes an orthologue of TAA genes and loss of FIB function resulted in pleiotropic abnormal phenotypes, such as small leaves with large lamina joint angles, abnormal vascular development, small panicles, abnormal organ identity and defects in root development, together with a reduction in internal IAA levels. Moreover, we found that auxin sensitivity and polar transport activity were altered in the fib mutant. From these results, we suggest that FIB plays a pivotal role in IAA biosynthesis in rice and that auxin biosynthesis, transport and sensitivity are closely interrelated. PMID:24654985

  11. Does light scattering affect the OCT quantitation of redox state of cytochrome oxidase in bone tissue?

    NASA Astrophysics Data System (ADS)

    Xu, Xiangqun; Wang, Ruikang K.; El Haj, Alicia

    2002-06-01

    In our previous report, we have presented the possibility of optical coherence tomography (OCT) to monitor the redox state of mitochondria enzyme Cytochrome oxidase (CytOx) in bone tissue. The previous results showed that reduction of the enzyme in periosteal tissue leads to a change in attenuation coefficient of 1.68 +/- 0.67mm-1 by OCT measurements. The new results from cultured cells fixed in 300 (mu) l agarose plug showed the difference in attenuation coefficient is 0.26+-0.10 mm-1 (n = 9) for 7x106 astrocytoma cells and 0.28+-0.13 mm-1 (n = 7) for 20x106 astrocytoma cells in agarose plug, respectively between cells with oxidised and reduced enzyme at 820nm. A decrease in attenuation coefficient of 0.35+-0.09 mm-1 (n = 4) for 10 million SKMES cells in agarose was also observed with the redox shift of CytOx. The absorption coefficient of the oxidized-reduced form of CytOx is measured approximately 8.4+-1.5x10-3/mm (n=3) and 8.2+-1.0x10-3/mm (n=3) at 820nm for astrocytoma cells and rat periosteum respectively by means of a biochemical assay. Thereby it can be seen that the change in attenuation coefficient of cultured cells with redox shift of CytOx mainly results from the scattering change.

  12. Donor age and cell passage affects differentiation potential of murine bone marrow-derived stem cells

    PubMed Central

    Kretlow, James D; Jin, Yu-Qing; Liu, Wei; Zhang, Wen Jie; Hong, Tan-Hui; Zhou, Guangdong; Baggett, L Scott; Mikos, Antonios G; Cao, Yilin

    2008-01-01

    Background Bone marrow-derived mesenchymal stem cells (BMSCs) are a widely researched adult stem cell population capable of differentiation into various lineages. Because many promising applications of tissue engineering require cell expansion following harvest and involve the treatment of diseases and conditions found in an aging population, the effect of donor age and ex vivo handling must be understood in order to develop clinical techniques and therapeutics based on these cells. Furthermore, there currently exists little understanding as to how these two factors may be influenced by one another. Results Differences in the adipogenic, chondrogenic, and osteogenic differentiation capacity of murine MSCs harvested from donor animals of different age and number of passages of these cells were observed. Cells from younger donors adhered to tissue culture polystyrene better and proliferated in greater number than those from older animals. Chondrogenic and osteogenic potential decreased with age for each group, and adipogenic differentiation decreased only in cells from the oldest donors. Significant decreases in differentiation potentials due to passage were observed as well for osteogenesis of BMSCs from the youngest donors and chondrogenesis of the cells from the oldest donors. Conclusion Both increasing age and the number of passages have lineage dependent effects on BMSC differentiation potential. Furthermore, there is an obvious interplay between donor age and cell passage that in the future must be accounted for when developing cell-based therapies for clinical use. PMID:18957087

  13. A long-term, observational cohort study on the safety of low-dose glucocorticoids in ankylosing spondylitis: adverse events and effects on bone mineral density, blood lipid and glucose levels and body mass index

    PubMed Central

    Zhang, Yu-Ping; Gong, Yao; Zeng, Qing Yu; Hou, Zhi-Duo; Xiao, Zheng-Yu

    2015-01-01

    Objectives This study aimed to investigate the risk of adverse events and effects on bone mineral density (BMD), blood lipid and glucose levels and body mass index (BMI) of low-dose glucocorticoid (GC) treatment in ankylosing spondylitis. Design We performed a retrospective, observational cohort study. Adverse effects were compared between GC users and non-GC users, and we analysed differences in the duration of GC exposure (no GC exposure, <6 months, 6 months to 2 years and >2 years). Setting Outpatient clinic in a tertiary general hospital in China, rheumatology follow-up visits over the past 30 years. Participants We included 830 patients with ankylosing spondylitis who were followed up for at least 6 months without a previous history or current complications of active gastrointestinal problems, hypertension, psychiatric or mental problems, diabetes mellitus, tuberculosis and hepatitis. The median follow-up time was 1.6 years (range 0.5–15 years, a total of 1801 patient-years). Results A total of 555 (66.9%) patients were treated with low-dose GCs, and the median cumulative duration of GC therapy was 1.3 years (range 0.1–8.5 years). Dermatological incidents, including acne, bruisability and cutaneous infections, were the most common adverse events, with a cumulative incidence rate of 5.4% (22.2 events per 1000 patient-years), followed by a puffy and rounded face (1.6%), symptoms of weight gain (1.1%) and serious infections (1.0%). The rates of all other types of adverse events were less than 1%. The GC groups (GC users and non-GC users) and the duration of GC therapy were not associated with the frequency of low BMD, dyslipidaemia, hyperglycaemia or obesity (p<0.05). Conclusions Adverse events during long-term treatment of low-dose GCs are limited. Low-dose GCs do not have an adverse effect on BMD, blood lipid and glucose levels and BMI. PMID:26041488

  14. Soy Isoflavones for Reducing Bone Loss (SIRBL) Study: Effect of a three-year trial on hormones, adverse events, and endometrial thickness in postmenopausal women

    PubMed Central

    Alekel, D. Lee; Genschel, Ulrike; Koehler, Kenneth J; Hofmann, Heike; Van Loan, Marta D; Beer, Bonnie S.; Hanson, Laura N; Peterson, Charles T; Kurzer, Mindy S

    2014-01-01

    Objectives To assess the overall safety and potential endometrial stimulation of soy isoflavone tablets consumed (3-year) by postmenopausal women. To determine the endometrial thickness response-to-treatment among compliant women, taking into account hormone concentrations and other hypothesized modifying factors. Methods We randomized healthy postmenopausal women (45.8–65.0 years) to placebo control or two doses (80 or 120 mg/day) of soy isoflavones at two sites. We used intent-to-treat (N=224) and compliant (>95%; N=208) analyses to assess circulating hormone concentrations, adverse events, and endometrial thickness (via transvaginal ultrasound). Results Median values for endometrial thickness (mm) declined from baseline through 36 mo. Nonparametric ANOVA for treatment differences among groups showed no differences in absolute (or percentage change) endometrial thickness at any time point (Chi-Square p-values ranged from 0.12–0.69), nor in circulating hormones at any time point. A greater number of adverse events for the genitourinary system (p=0.005) was noted in the 80 compared to 120 mg/day group, whereas other systems showed no treatment effects. The model predicting the endometrial thickness response-(using natural logarithm)-to-treatment with compliant women across time points was significant (p<0.0001), indicating that estrogen exposure (p=0.0013), plasma 17 β-estradiol (p=0.0086), and alcohol intake (p=0.023) contributed significantly to the response. Neither the 80 (p=0.57) nor 120 (p=0.43) mg/day dose exerted an effect on endometrial thickness across time. Conclusions Our RCT verified the long-term overall safety of consuming soy isoflavone tablets by postmenopausal women who displayed excellent compliance. We found no evidence of a treatment effect on endometrial thickness, adverse events, or circulating hormone concentrations, most notably thyroid function, during a three year period. PMID:25003624

  15. Caffeic acid phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to ionizing radiation without affecting bone marrow radioresponse

    SciTech Connect

    Chen, Y.-J.; Liao, H.-F.; Tsai, T.-H.; Wang, S.-Y.; Shiao, M.-S. . E-mail: msshiao@vghtpe.gov.tw

    2005-11-15

    Purpose: Caffeic acid phenethyl ester (CAPE), a component of propolis, was reported capable of depleting glutathione (GSH). We subsequently examined the radiosensitizing effect of CAPE and its toxicity. Methods and Materials: The effects of CAPE on GSH level, GSH metabolism enzyme activities, NF-{kappa}B activity, and radiosensitivity in mouse CT26 colorectal adenocarcinoma cells were determined. BALB/c mouse with CT26 cells implantation was used as a syngeneic in vivo model for evaluation of treatment and toxicity end points. Results: CAPE entered CT26 cells rapidly and depleted intracellular GSH in CT26 cells, but not in bone marrow cells. Pretreatment with nontoxic doses of CAPE significantly enhanced cell killing by ionizing radiation (IR) with sensitizer enhancement ratios up to 2.2. Pretreatment of CT26 cells with N-acetyl-L-cysteine reversed the GSH depletion activity and partially blocked the radiosensitizing effect of CAPE. CAPE treatment in CT26 cells increased glutathione peroxidase, decreased glutathione reductase, and did not affect glutathione S-transferase or {gamma}-glutamyl transpeptidase activity. Radiation activated NF-{kappa}B was reversed by CAPE pretreatment. In vivo study revealed that pretreatment with CAPE before IR resulted in greater inhibition of tumor growth and prolongation of survival in comparison with IR alone. Pretreatment with CAPE neither affected body weights nor produced hepatic, renal, or hematopoietic toxicity. Conclusions: CAPE sensitizes CT26 colorectal adenocarcinoma to IR, which may be via depleting GSH and inhibiting NF-{kappa}B activity, without toxicity to bone marrow, liver, and kidney.

  16. Does bone morphogenetic protein 6 (BMP6) affect female fertility in the mouse?

    PubMed

    Sugiura, Koji; Su, You-Qiang; Eppig, John J

    2010-12-01

    Bone morphogenetic protein 6 (BMP6) is a transforming growth factor beta superfamily member produced by mammalian oocytes as well as other cell types. Despite well-characterized effects of recombinant BMP6 on granulosa cells in vitro, the function of BMP6 in vivo has been ill-defined. Therefore, the effects of genetic deletion of the Bmp6 gene on female mouse fertility were assessed. The mean litter size of Bmp6(-/-) females was reduced by 22% (P < 0.05) compared to Bmp6(+/+) controls. Not only did Bmp6(-/-) females naturally ovulate 24% fewer eggs, but competence of in vitro-matured oocytes to complete preimplantation development after fertilization in vitro was decreased by 50%. No apparent effect of Bmp6 deletion on either the morphology or the dynamics of follicular development was apparent. Nevertheless, levels of luteinizing hormone (LH)/human chorionic gonadotropin (hCG)-induced transcripts, which encode proteins required for cumulus expansion (HAS2, PTGS2, PTX3, and TNFAIP6), and of epidermal growth factor-like peptides (AREG, BTC, and EREG) were lower in Bmp6(-/-) mice than in controls after administration of a reduced dose of hCG (1 IU) in vivo. LH receptor (Lhcgr) transcript levels were not significantly lower in Bmp6(-/-) granulosa cells, suggesting that BMP6 is required for processes downstream of LH receptors. To assess whether another oocyte-derived BMP, BMP15, could have BMP6-redundant functions in vivo, the fertility of Bmp15/Bmp6 double mutants was assessed. Fertility was not significantly reduced in double-homozygous mutants compared with that in double-heterozygous controls. Therefore, BMP6 promotes normal fertility in female mice, at least in part, by enabling appropriate responses to LH and normal oocyte quality. Thus, Bmp6 probably is part of the complex genetic network that determines female fertility. PMID:20702851

  17. Evaluating bone quality in patients with chronic kidney disease

    PubMed Central

    Malluche, Hartmut H.; Porter, Daniel S.; Pienkowski, David

    2013-01-01

    Bone of normal quality and quantity can successfully endure physiologically imposed mechanical loads. Chronic kidney disease–mineral and bone disorder (CKD–MBD) adversely affects bone quality through alterations in bone turnover and mineralization, whereas bone quantity is affected through changes in bone volume. Changes in bone quality can be associated with altered bone material, structure, or microdamage, which can result in an elevated rate of fracture in patients with CKD–MBD. Fractures cannot always be explained by reduced bone quantity and, therefore, bone quality should be assessed with a variety of techniques from the macro-organ level to the nanoscale level. In this Review, we demonstrate the importance of evaluating bone from multiple perspectives and hierarchical levels to understand CKD–MBD-related abnormalities in bone quality. Understanding the relationships between variations in material, structure, microdamage, and mechanical properties of bone in patients with CKD–MBD should aid in the development of new modalities to prevent, or treat, these abnormalities. PMID:24100399

  18. Vaccenic acid and trans fatty acid isomers from partially hydrogenated oil both adversely affect LDL cholesterol: a double-blind, randomized controlled trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Evidence of the adverse effects of industrially-produced trans fatty acids (iTFA) on risk of cardiovascular disease is consistent and well documented in the scientific literature; however, the cardiovascular effects of naturally-occurring TFA synthesized in ruminant animals (rTFA), such as vaccenic ...

  19. Increasing the number of unloading/reambulation cycles does not adversely impact body composition and lumbar bone mineral density but reduces tissue sensitivity

    NASA Astrophysics Data System (ADS)

    Gupta, Shikha; Manske, Sarah L.; Judex, Stefan

    2013-11-01

    A single exposure to hindlimb unloading leads to changes in body mass, body composition and bone, but the consequences of multiple exposures are not yet understood. Within a 18 week period, adult C57BL/6 male mice were exposed to 1 (1x-HLU), 2 (2x-HLU) or 3 (3x-HLU) cycles of 2 weeks of hindlimb unloading (HLU) followed by 4 weeks of reambulation (RA), or served as ambulatory age-matched controls. In vivo μCT longitudinally tracked changes in abdominal adipose and lean tissues, lumbar vertebral apparent volumetric bone mineral density (vBMD) and upper hindlimb muscle cross-sectional area before and after the final HLU and RA cycle. During the final HLU cycle, significant decreases in total adipose tissue and vertebral vBMD in the three experimental groups occurred such that there were no significant between-group differences at the beginning of the final RA cycle. However, the magnitude of the HLU induced losses diminished in mice undergoing their 2nd or 3rd HLU cycle. Irrespective of the number of HLU/RA cycles, total adipose tissue and vertebral vBMD recovered and were no different from age-matched controls after the final RA period. In contrast, upper hindlimb muscle cross-sectional area was significantly lower than controls in all unloaded groups after the final RA period. These results suggest that tissues in the abdominal region are more resilient to multiple bouts of unloading and more amenable to recovery during reambulation than the peripheral musculoskeletal system.

  20. Does the Time of Postoperative Bisphosphonate Administration Affect the Bone Union in Osteoporotic Intertrochanteric Fracture of Femur?

    PubMed Central

    Cho, Yoon Je; Chun, Young Soo; Kang, Joon Soon; Jung, Gwang Young; Lee, Jun Hee

    2015-01-01

    Purpose This study was designed to investigate the effect of bisphosphonate administration starting time on bone healing and to identify the best administration time following surgical treatment of osteoporotic intertrochanteric fractures. Materials and Methods Two hundreds and eighty four patients (284 hips; 52 males, 232 females) who underwent surgery following osteoporotic intertrochanteric fracture from December 2002 to December 2012 were retrospectively analyzed. The average follow-up period was 68.4 months. The patients were divided into three groups according to the time of bisphosphonate administration after operation: 1 week (group A; n=102), 1 month (group B; n=89), and 3 months (group C; n=93). Koval scores and change of Koval scores 1 year after operation were used for clinical evaluation. For radiologic evaluation, the time of callus appearance across the fracture line on sagittal and coronal radiographs and the time to absence of pain during hip motion was judged as the time of bone union. Results Koval scores one year after surgery for groups A, B, and C were 2.44, 2.36, and 2.43 (P=0.895), respectively. The mean time of union was 12.4, 11.9, and 12.3 weeks after operation in the three groups (P=0.883), respectively. There were zero cases of nonunion. There were 3, 5, and 7 cases of fixative displacement in the three groups, respectively, but the distribution showed no significant difference (P>0.472). Conclusion The initiating time of bisphosphonate administration following surgery does not affect the clinical outcomes in patients with osteoporotic intertrochanteric fracture. PMID:27536634

  1. How do changes to plate thickness, length, and face-connectivity affect femoral cancellous bone's density and surface area? An investigation using regular cellular models.

    PubMed

    Anderson, I A; Carman, J B

    2000-03-01

    Models of regular cellular-solids representing femoral head 'medial group' bone were used to (1) compare thickness data for plate-like and beam-like structures at realistic surface areas and densities; (2) test the validity of a standard formula for trabecular thickness (Tb.Th); and (3) study how systematic changes in cancellous bone thicknesses, spacing, and face-connectivity affect relative density and surface area. Models of different face-connectivities, produced by plate removal from the unit cell, were fitted to bone density and surface area data. The medial group bone was anisotropic: the supero-inferior (SI) direction was the principal direction for bone plate alignment and the plane normal to this had the largest number of bone/void intersections per unit line length (P(I)). A comparison of boundary perimeter per unit area data, in planes normal to SI, with surface area data placed the medial group bone between prismatic structures in which walls are parallel to one principal direction and isotropic structures. Selective removal of plates from a closed-cell model produced a similar result. For the same relative density and surface-area, plate-like models had significantly thinner cross-sections than beam-like models. The formula for Tb.Th produced overestimates of model plate thickness by up to 20% at realistic femoral cancellous densities. Trends in data on surface area to volume ratio and density observed on sampled medial group bone could be simulated by plate thickness changes on models of intermediate face-connectivity (approximately 1.5) or by plate removal from models with relatively thick and short (low aspect-ratio) plates. The latter mechanism is unrealistic for it resulted in beam-like structures at low 'medial group' densities, an architecture unlike the predominantly plate-like bone in the sample. PMID:10673116

  2. Optimizing Bone Health in Duchenne Muscular Dystrophy

    PubMed Central

    Buckner, Jason L.; Bowden, Sasigarn A.; Mahan, John D.

    2015-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive muscle weakness, with eventual loss of ambulation and premature death. The approved therapy with corticosteroids improves muscle strength, prolongs ambulation, and maintains pulmonary function. However, the osteoporotic impact of chronic corticosteroid use further impairs the underlying reduced bone mass seen in DMD, leading to increased fragility fractures of long bones and vertebrae. These serious sequelae adversely affect quality of life and can impact survival. The current clinical issues relating to bone health and bone health screening methods in DMD are presented in this review. Diagnostic studies, including biochemical markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry (DXA), as well as spinal imaging using densitometric lateral spinal imaging, and treatment to optimize bone health in patients with DMD are discussed. Treatment with bisphosphonates offers a method to increase bone mass in these children; oral and intravenous bisphosphonates have been used successfully although treatment is typically reserved for children with fractures and/or bone pain with low bone mass by DXA. PMID:26124831

  3. Nasopharyngeal carcinoma with bone marrow metastasis.

    PubMed

    Zen, H G; Jame, J M; Chang, A Y; Li, W Y; Law, C K; Chen, K Y; Lin, C Z

    1991-02-01

    Five of 23 patients with recurrent nasopharyngeal carcinoma (NPC) were diagnosed to have bone marrow metastasis. They all had advanced local-regional disease, and were treated with neoadjuvant chemotherapy and definitive radiotherapy after the initial diagnosis. Bone marrow metastasis developed 4-24 months later. The clinical features were anemia (5 of 5), leukopenia (3 of 5), thrombocytopenia (4 of 5), sepsis (3 of 5), tenderness of the sternum (3 of 5), and fever (4 of 5). Patients frequently had elevation of serum lactic dehydrogenase (LDH), alkaline phosphatase (ALK-P), and IgG and IgA antibody titers to Epstein-Barr viral capsid antigen when bone marrow involvement was diagnosed. However, clinical manifestations and laboratory tests were not specific. It is important that three patients had normal bone scans. All five patients had a rapid downhill course; four patients died within 23 days, and the fifth 3 months after the diagnosis of bone marrow metastasis. We concluded that bone marrow was a common metastatic site in NPC patients. Bone marrow metastasis adversely affected patients' survival and required a high index of suspicion for diagnosis. We suggested that bone marrow biopsy should be considered as a routine staging procedure in NPC patients and indicated especially when patients presented with abnormal blood counts, sepsis, bone pain, or tenderness of the sternum. It may be positive in the face of a normal bone scan. PMID:1987743

  4. OPG Treatment Prevents Bone Loss During Lactation But Does Not Affect Milk Production or Maternal Calcium Metabolism.

    PubMed

    Ardeshirpour, Laleh; Dumitru, Cristina; Dann, Pamela; Sterpka, John; VanHouten, Joshua; Kim, Wonnam; Kostenuik, Paul; Wysolmerski, John

    2015-08-01

    Lactation is associated with increased bone turnover and rapid bone loss, which liberates skeletal calcium used for milk production. Previous studies suggested that an increase in the skeletal expression of receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells ligand (RANKL) coupled with a decrease in osteoprotegerin (OPG) levels likely triggered bone loss during lactation. In this study, we treated lactating mice with recombinant OPG to determine whether bone loss during lactation was dependent on RANKL signaling and whether resorption of the maternal skeleton was required to support milk production. OPG treatment lowered bone resorption rates and completely prevented bone loss during lactation but, surprisingly, did not decrease osteoclast numbers. In contrast, OPG was quite effective at lowering osteoblast numbers and inhibiting bone formation in lactating mice. Furthermore, treatment with OPG during lactation prevented the usual anabolic response associated with reversal of lactational bone loss after weaning. Preventing bone loss had no appreciable effect on milk production, milk calcium levels, or maternal calcium homeostasis when mice were on a standard diet. However, when dietary calcium was restricted, treatment with OPG caused maternal hypocalcemia, maternal death, and decreased milk production. These studies demonstrate that RANKL signaling is a requirement for bone loss during lactation, and suggest that osteoclast activity may be required to increase osteoblast numbers during lactation in preparation for the recovery of bone mass after weaning. These data also demonstrate that maternal bone loss is not absolutely required to supply calcium for milk production unless dietary calcium intake is inadequate. PMID:25961842

  5. OPG Treatment Prevents Bone Loss During Lactation But Does Not Affect Milk Production or Maternal Calcium Metabolism

    PubMed Central

    Ardeshirpour, Laleh; Dumitru, Cristina; Dann, Pamela; Sterpka, John; VanHouten, Joshua; Kim, Wonnam; Kostenuik, Paul

    2015-01-01

    Lactation is associated with increased bone turnover and rapid bone loss, which liberates skeletal calcium used for milk production. Previous studies suggested that an increase in the skeletal expression of receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells ligand (RANKL) coupled with a decrease in osteoprotegerin (OPG) levels likely triggered bone loss during lactation. In this study, we treated lactating mice with recombinant OPG to determine whether bone loss during lactation was dependent on RANKL signaling and whether resorption of the maternal skeleton was required to support milk production. OPG treatment lowered bone resorption rates and completely prevented bone loss during lactation but, surprisingly, did not decrease osteoclast numbers. In contrast, OPG was quite effective at lowering osteoblast numbers and inhibiting bone formation in lactating mice. Furthermore, treatment with OPG during lactation prevented the usual anabolic response associated with reversal of lactational bone loss after weaning. Preventing bone loss had no appreciable effect on milk production, milk calcium levels, or maternal calcium homeostasis when mice were on a standard diet. However, when dietary calcium was restricted, treatment with OPG caused maternal hypocalcemia, maternal death, and decreased milk production. These studies demonstrate that RANKL signaling is a requirement for bone loss during lactation, and suggest that osteoclast activity may be required to increase osteoblast numbers during lactation in preparation for the recovery of bone mass after weaning. These data also demonstrate that maternal bone loss is not absolutely required to supply calcium for milk production unless dietary calcium intake is inadequate. PMID:25961842

  6. Textural and rheological properties of Pacific whiting surimi as affected by nano-scaled fish bone and heating rates.

    PubMed

    Yin, Tao; Park, Jae W

    2015-08-01

    Textural and rheological properties of Pacific whiting (PW) surimi were investigated at various heating rates with the use of nano-scaled fish bone (NFB) and calcium chloride. Addition of NFB and slow heating improved gel strength significantly. Activity of endogenous transglutaminase (ETGase) from PW surimi was markedly induced by both NFB calcium and calcium chloride, showing an optimal temperature at 30°C. Initial storage modulus increased as NFB calcium concentration increased and the same trend was maintained throughout the temperature sweep. Rheograms with temperature sweep at slow heating rate (1°C/min) exhibited two peaks at ∼ 35°C and ∼ 70°C. However, no peak was observed during temperature sweep from 20 to 90°C at fast heating rate (20°C/min). Protein patterns of surimi gels were affected by both heating rate and NFB calcium concentration. Under slow heating, myosin heavy chain intensity decreased with NFB calcium concentration, indicating formation of ε-(γ-glutamyl) lysine cross-links by ETGase and NFB calcium ion. PMID:25766799

  7. Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis).

    PubMed

    McGee, Meghan E; Maki, Aaron J; Johnson, Steven E; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

    2008-02-01

    Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate that bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis. PMID:18037367

  8. Cyclosporin A does not affect the absolute rate of cortical bone resorption at the organ level in the growing rat.

    PubMed

    Klein, L; Lemel, M S; Wolfe, M S; Shaffer, J

    1994-10-01

    The weanling rat, an animal model of rapid bone turnover, was used to evaluate the effects of various doses of cyclosporin A (CsA) on various bones during different time periods. Sprague-Dawley male rats were extensively prelabeled with 3H-tetracycline during 1-3 weeks of age. At 4 weeks of age, four groups of rats were given daily subcutaneous injections: vehicle or CsA--low dose (10 mg/kg), intermediary dose (20 mg/kg), or high dose (30 mg/kg) for 7, 14, or 28 days. Three different whole bones--the femur (low turnover), scapula (moderate turnover), and lumbar-6 vertebra (high turnover) were harvested intact at 4, 5, 6, and 8 weeks of age. The whole bones were assayed weekly for total dry defatted weight, calcium mass (formation), and loss of 3H-tetracycline (bone resorption) following treatment with CsA. Serum CsA levels, calcium creatinine, and alkaline phosphatase were measured weekly. Significant decreases in serum calcium and alkaline phosphatase were observed at 1 and 2 weeks, and were normalized by 4 weeks of treatment. No significant changes in serum creatinine were noted. For all three doses of CsA, no effect was observed on the absolute rate of cortical bone resorption of three different, whole bones over three time periods. Body weight and bone formation in treated animals was significantly smaller in a dose- and time-related fashion compared with control animals at sacrifice. However, compared with the initial control animals, body weights and bone masses of the final treated animals were much larger, suggesting that the smaller bone masses were due to insufficient growth and slow gain in bone mass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7820781

  9. Cabozantinib inhibits growth of androgen-sensitive and castration-resistant prostate cancer and affects bone remodeling.

    PubMed

    Nguyen, Holly M; Ruppender, Nazanin; Zhang, Xiaotun; Brown, Lisha G; Gross, Ted S; Morrissey, Colm; Gulati, Roman; Vessella, Robert L; Schimmoller, Frauke; Aftab, Dana T; Corey, Eva

    2013-01-01

    Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa), cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemistry and tissue microarrays containing normal prostate, primary PCa, and soft tissue and bone metastases, our data show that levels of MET, P-MET, and VEGFR2 are increasing during PCa progression. Our data also show that the expression of cabozantinib targets are particularly pronounced in bone metastases. To evaluate cabozantinib efficacy on PCa growth in the bone environment and in soft tissues we used androgen-sensitive LuCaP 23.1 and castration-resistant C4-2B PCa tumors. In vivo, cabozantinib inhibited the growth of PCa in bone as well as growth of subcutaneous tumors. Furthermore, cabozantinib treatment attenuated the bone response to the tumor and resulted in increased normal bone volume. In summary, the expression pattern of cabozantinib targets in primary and castration-resistant metastatic PCa, and its efficacy in two different models of PCa suggest that this agent has a strong potential for the effective treatment of PCa at different stages of the disease. PMID:24205338

  10. High d(+)-fructose diet adversely affects testicular weight gain in weaning rats─protection by moderate d(+)-glucose diet.

    PubMed

    Shibata, Katsumi; Fukuwatari, Tsutomu

    2013-01-01

    The use of high D(+)-fructose corn syrup has increased over the past several decades in the developed countries, while overweight and obesity rates and the related diseases have risen dramatically. However, we found that feeding a high D(+)-fructose diet (80% D(+)-fructose as part of the diet) to weaning rats for 21 days led to reduced food intake (50% less, P < 0.0001) and thus delayed the weight gains in the body (40% less, P < 0.0001) and testes (40% less, P < 0.0001) compared to the no D(+)-fructose diet. We also challenged a minimum requirement of dietary D(+)-glucose for preventing the adverse effects of D(+)-fructose, such as lower food intake and reduction of body weight and testicular weight; the minimum requirement of D(+)-glucose was ≈23% of the diet. This glucose amount may be the minimum requirement of exogenous glucose for reducing weight gain. PMID:23935370

  11. Dicer ablation in osteoblasts by Runx2 driven cre-loxP recombination affects bone integrity, but not glucocorticoid-induced suppression of bone formation.

    PubMed

    Liu, Peng; Baumgart, Mario; Groth, Marco; Wittmann, Jürgen; Jäck, Hans-Martin; Platzer, Matthias; Tuckermann, Jan P; Baschant, Ulrike

    2016-01-01

    Glucocorticoid-induced osteoporosis (GIO) is one of the major side effects of long-term glucocorticoid (GC) therapy mediated mainly via the suppression of bone formation and osteoblast differentiation independently of GC receptor (GR) dimerization. Since microRNAs play a critical role in osteoblast differentiation processes, we investigated the role of Dicer dependent microRNAs in the GC-induced suppression of osteoblast differentiation. MicroRNA sequencing of dexamethasone-treated wild-type and GR dimer-deficient mesenchymal stromal cells revealed GC-controlled miRNA expression in a GR dimer-dependent and GR dimer-independent manner. To determine the functional relevance of mature miRNAs in GC-induced osteoblast suppression, mice with an osteoblast-specific deletion of Dicer (Dicer(Runx2Cre)) were exposed to glucocorticoids. In vitro generated Dicer-deficient osteoblasts were treated with dexamethasone and analyzed for proliferation, differentiation and mineralization capacity. In vivo, abrogation of Dicer-dependent miRNA biogenesis in osteoblasts led to growth retardation and impaired bone formation. However, subjecting these mice to GIO showed that bone formation was similar reduced in Dicer(Runx2Cre) mice and littermate control mice upon GC treatment. In line, differentiation of Dicer deficient osteoblasts was suppressed to the same extent as wild type cells by GC treatment. Therefore, Dicer-dependent small RNA biogenesis in osteoblasts plays only a minor role in the pathogenesis of GC-induced inhibition of bone formation. PMID:27554624

  12. Dicer ablation in osteoblasts by Runx2 driven cre-loxP recombination affects bone integrity, but not glucocorticoid-induced suppression of bone formation

    PubMed Central

    Liu, Peng; Baumgart, Mario; Groth, Marco; Wittmann, Jürgen; Jäck, Hans-Martin; Platzer, Matthias; Tuckermann, Jan P.; Baschant, Ulrike

    2016-01-01

    Glucocorticoid-induced osteoporosis (GIO) is one of the major side effects of long-term glucocorticoid (GC) therapy mediated mainly via the suppression of bone formation and osteoblast differentiation independently of GC receptor (GR) dimerization. Since microRNAs play a critical role in osteoblast differentiation processes, we investigated the role of Dicer dependent microRNAs in the GC-induced suppression of osteoblast differentiation. MicroRNA sequencing of dexamethasone-treated wild-type and GR dimer-deficient mesenchymal stromal cells revealed GC-controlled miRNA expression in a GR dimer-dependent and GR dimer-independent manner. To determine the functional relevance of mature miRNAs in GC-induced osteoblast suppression, mice with an osteoblast-specific deletion of Dicer (DicerRunx2Cre) were exposed to glucocorticoids. In vitro generated Dicer-deficient osteoblasts were treated with dexamethasone and analyzed for proliferation, differentiation and mineralization capacity. In vivo, abrogation of Dicer-dependent miRNA biogenesis in osteoblasts led to growth retardation and impaired bone formation. However, subjecting these mice to GIO showed that bone formation was similar reduced in DicerRunx2Cre mice and littermate control mice upon GC treatment. In line, differentiation of Dicer deficient osteoblasts was suppressed to the same extent as wild type cells by GC treatment. Therefore, Dicer-dependent small RNA biogenesis in osteoblasts plays only a minor role in the pathogenesis of GC-induced inhibition of bone formation. PMID:27554624

  13. Consumption of different sources of omega-3 polyunsaturated fatty acids by growing female rats affects long bone mass and microarchitecture.

    PubMed

    Lukas, Robin; Gigliotti, Joseph C; Smith, Brenda J; Altman, Stephanie; Tou, Janet C

    2011-09-01

    Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) consumption has been reported to improve bone health. However, sources of ω-3 PUFAs differ in the type of fatty acids and structural form. The study objective was to determine the effect of various ω-3 PUFAs sources on bone during growth. Young (age 28d) female Sprague-Dawley rats were randomly assigned (n=10/group) to a high fat 12% (wt) diet consisting of either corn oil (CO) or ω-3 PUFA rich, flaxseed (FO), krill (KO), menhaden (MO), salmon (SO) or tuna (TO) for 8 weeks. Bone mass was assessed by dual-energy X-ray absorptiometry (DXA) and bone microarchitecture by micro-computed tomography (μCT). Bone turnover markers were measured by enzyme immunoassay. Lipid peroxidation was measured by calorimetric assays. Results showed that rats fed TO, rich in docosahexaenoic acid (DHA, 22:6ω-3) had higher (P<0.009) tibial bone mineral density (BMD) and bone mineral content (BMC) and lower (P=0.05) lipid peroxidation compared to the CO-fed rats. Reduced lipid peroxidation was associated with increased tibial BMD (r2=0.08, P=0.02) and BMC (r2=0.71, P=0.01). On the other hand, rats fed FO or MO, rich in alpha-linolenic acid (ALA, 18:3ω-3), improved bone microarchitecture compared to rats fed CO or SO. Serum osteocalcin was higher (P=0.03) in rats fed FO compared to rats fed SO. Serum osteocalcin was associated with improved trabecular bone microarchitecture. The animal study results suggest consuming a variety of ω-3 PUFA sources to promote bone health during the growth stage. PMID:21672645

  14. Altitude, pasture type, and sheep breed affect bone metabolism and serum 25-hydroxyvitamin D in grazing lambs.

    PubMed

    Willems, Helen; Leiber, Florian; Kohler, Martina; Kreuzer, Michael; Liesegang, Annette

    2013-05-15

    This study aimed to investigate the bone development of two mountain sheep breeds during natural summer grazing either in the lowlands or on different characteristic alpine pastures. Pasture types differed in topographic slope, plant species composition, general nutritional feeding value, Ca and P content, and Ca:P ratio of herbage. Twenty-seven Engadine sheep (ES) lambs and 27 Valaisian Black Nose sheep (VS) lambs were divided into four groups of 6 to 7 animals per breed and allocated to three contrasting alpine pasture types and one lowland pasture type. The lambs were slaughtered after 9 wk of experimental grazing. The steep alpine pastures in combination with a high (4.8) to very high (13.6) Ca:P ratio in the forage decreased total bone mineral content as measured in the middle of the left metatarsus of the lambs from both breeds, and cortical bone mineral content and cortical bone mineral density of ES lambs. Breed × pasture type interactions occurred in the development of total and cortical bone mineral content, and in cortical thickness, indicating that bone metabolism of different genotypes obviously profited differently from the varying conditions. An altitude effect occurred for 25-hydroxyvitamin D with notably higher serum concentrations on the three alpine sites, and a breed effect led to higher concentrations for ES than VS. Despite a high variance, there were pasture-type effects on serum markers of bone formation and resorption. PMID:23471950

  15. Migration, neighborhoods, and networks: approaches to understanding how urban environmental conditions affect syndemic adverse health outcomes among gay, bisexual and other men who have sex with men.

    PubMed

    Egan, James E; Frye, Victoria; Kurtz, Steven P; Latkin, Carl; Chen, Minxing; Tobin, Karin; Yang, Cui; Koblin, Beryl A

    2011-04-01

    Adopting socioecological, intersectionality, and lifecourse theoretical frameworks may enhance our understanding of the production of syndemic adverse health outcomes among gay, bisexual and other men who have sex with men (MSM). From this perspective, we present preliminary data from three related studies that suggest ways in which social contexts may influence the health of MSM. The first study, using cross-sectional data, looked at migration of MSM to the gay resort area of South Florida, and found that amount of time lived in the area was associated with risk behaviors and HIV infection. The second study, using qualitative interviews, observed complex interactions between neighborhood-level social environments and individual-level racial and sexual identity among MSM in New York City. The third study, using egocentric network analysis with a sample of African American MSM in Baltimore, found that sexual partners were more likely to be found through face-to-face means than the Internet. They also observed that those who co-resided with a sex partner had larger networks of people to depend on for social and financial support, but had the same size sexual networks as those who did not live with a partner. Overall, these findings suggest the need for further investigation into the role of macro-level social forces on the emotional, behavioral, and physical health of urban MSM. PMID:21369730

  16. Trans-generational exposure to low levels of rhodamine B does not adversely affect litter size or liver function in murine mucopolysaccharidosis type IIIA.

    PubMed

    Roberts, Ainslie L K; Fletcher, Janice M; Moore, Lynette; Byers, Sharon

    2010-01-01

    MPS IIIA is a lysosomal storage disorder caused by mutations in the sulphamidase gene, resulting in the accumulation of heparan sulphate glycosaminoglycans (HS GAGs). Symptoms predominantly manifest in the CNS and there is no current therapy that effectively addresses neuropathology in MPS IIIA patients. Recent studies in MPS IIIA mice have shown that rhodamine B substrate deprivation therapy (SDT) (also termed substrate reduction therapy/SRT) inhibits GAG biosynthesis and, improves both somatic and CNS disease pathology. Acute overexposure to high doses of rhodamine B results in liver toxicity and is detrimental to reproductive ability. However, the long-term effects of decreasing GAG synthesis, at the low dose sufficient to alter neurological function are unknown. A trans-generational study was therefore initiated to evaluate the continuous exposure of rhodamine B treatment in MPS IIIA mice over 4 generations, including treatment during pregnancy. No alterations in litter size, liver histology or liver function were observed. Overall, there are no long-term issues with the administration of rhodamine B at the low dose tested and no adverse effects were noted during pregnancy in mice. PMID:20650670

  17. Rock Glacier Outflows May Adversely Affect Lakes: Lessons from the Past and Present of Two Neighboring Water Bodies in a Crystalline-Rock Watershed

    PubMed Central

    2014-01-01

    Despite the fact that rock glaciers are one of the most common geomorphological expressions of mountain permafrost, the impacts of their solute fluxes on lakes still remain largely obscure. We examined water and sediment chemistry, and biota of two neighboring water bodies with and without a rock glacier in their catchments in the European Alps. Paleolimnological techniques were applied to track long-term temporal trends in the ecotoxicological state of the water bodies and to establish their baseline conditions. We show that the active rock glacier in the mineralized catchment of Lake Rasass (RAS) represents a potent source of acid rock drainage that results in enormous concentrations of metals in water, sediment, and biota of RAS. The incidence of morphological abnormalities in the RAS population of Pseudodiamesa nivosa, a chironomid midge, is as high as that recorded in chironomid populations inhabiting sites heavily contaminated by trace metals of anthropogenic origin. The incidence of morphological deformities in P. nivosa of ∼70% persisted in RAS during the last 2.5 millennia and was ∼40% in the early Holocene. The formation of RAS at the toe of the rock glacier most probably began at the onset of acidic drainage in the freshly deglaciated area. The present adverse conditions are not unprecedented in the lake’s history and cannot be associated exclusively with enhanced thawing of the rock glacier in recent years. PMID:24804777

  18. Rock glacier outflows may adversely affect lakes: lessons from the past and present of two neighboring water bodies in a crystalline-rock watershed.

    PubMed

    Ilyashuk, Boris P; Ilyashuk, Elena A; Psenner, Roland; Tessadri, Richard; Koinig, Karin A

    2014-06-01

    Despite the fact that rock glaciers are one of the most common geomorphological expressions of mountain permafrost, the impacts of their solute fluxes on lakes still remain largely obscure. We examined water and sediment chemistry, and biota of two neighboring water bodies with and without a rock glacier in their catchments in the European Alps. Paleolimnological techniques were applied to track long-term temporal trends in the ecotoxicological state of the water bodies and to establish their baseline conditions. We show that the active rock glacier in the mineralized catchment of Lake Rasass (RAS) represents a potent source of acid rock drainage that results in enormous concentrations of metals in water, sediment, and biota of RAS. The incidence of morphological abnormalities in the RAS population of Pseudodiamesa nivosa, a chironomid midge, is as high as that recorded in chironomid populations inhabiting sites heavily contaminated by trace metals of anthropogenic origin. The incidence of morphological deformities in P. nivosa of ∼70% persisted in RAS during the last 2.5 millennia and was ∼40% in the early Holocene. The formation of RAS at the toe of the rock glacier most probably began at the onset of acidic drainage in the freshly deglaciated area. The present adverse conditions are not unprecedented in the lake's history and cannot be associated exclusively with enhanced thawing of the rock glacier in recent years. PMID:24804777

  19. Plasmid load adversely affects growth and gluconic acid secretion ability of mineral phosphate-solubilizing rhizospheric bacterium Enterobacter asburiae PSI3 under P limited conditions.

    PubMed

    Sharma, Vikas; Archana, G; Naresh Kumar, G

    2011-01-20

    Effect of the metabolic load caused by the presence of plasmids on mineral phosphate-solubilizing (MPS) Enterobacter asburiae PSI3, was monitored with four plasmid cloning vectors and one native plasmid, varying in size, nature of the replicon, copy number and antibiotic resistance genes. Except for one plasmid, the presence of all other plasmids in E. asburiae PSI3 resulted in the loss of the MPS phenotype as reflected by the failure to bring about a drop in pH and release soluble P when grown in media containing rock phosphate (RP) as the sole P source. When 100 μM soluble P was supplemented along with RP, the adverse effects of plasmids on MPS phenotype and on growth parameters was reduced for some plasmid bearing derivatives, as monitored in terms of specific growth rates, glucose consumed, gluconic acids yields and P released. When 10 mM of soluble P as the only P source, was added to the medium all transformants showed growth and pH drop comparable with native strain. It may be concluded that different plasmids impose, to varying extents, a metabolic load in the phosphate-solubilizing bacterium E. asburiae PSI3 and results in diminishing its growth and P-solubilizing ability in P deficient conditions. PMID:20171856

  20. Migration, Neighborhoods, and Networks: Approaches to Understanding How Urban Environmental Conditions Affect Syndemic Adverse Health Outcomes Among Gay, Bisexual and Other Men Who Have Sex with Men

    PubMed Central

    Egan, James E.; Kurtz, Steven P.; Latkin, Carl; Chen, Minxing; Tobin, Karin; Yang, Cui; Koblin, Beryl A.

    2011-01-01

    Adopting socioecological, intersectionality, and lifecourse theoretical frameworks may enhance our understanding of the production of syndemic adverse health outcomes among gay, bisexual and other men who have sex with men (MSM). From this perspective, we present preliminary data from three related studies that suggest ways in which social contexts may influence the health of MSM. The first study, using cross-sectional data, looked at migration of MSM to the gay resort area of South Florida, and found that amount of time lived in the area was associated with risk behaviors and HIV infection. The second study, using qualitative interviews, observed complex interactions between neighborhood-level social environments and individual-level racial and sexual identity among MSM in New York City. The third study, using egocentric network analysis with a sample of African American MSM in Baltimore, found that sexual partners were more likely to be found through face-to-face means than the Internet. They also observed that those who co-resided with a sex partner had larger networks of people to depend on for social and financial support, but had the same size sexual networks as those who did not live with a partner. Overall, these findings suggest the need for further investigation into the role of macro-level social forces on the emotional, behavioral, and physical health of urban MSM. PMID:21369730

  1. Treatment of subclinical hypothyroidism does not affect bone mass as determined by dual-energy X-ray absorptiometry, peripheral quantitative computed tomography and quantitative bone ultrasound in Spanish women

    PubMed Central

    Roncero-Martin, Raul; Calderon-Garcia, Julian F.; Santos-Vivas, Mercedes; Vera, Vicente; Martínez-Alvárez, Mariana; Rey-Sanchez, Purificación

    2015-01-01

    Introduction The results of studies examining the influence of subclinical hypothyroidism (SCH) and levothyroxine (L-T4) replacement therapy on bone have generated considerable interest but also controversy. The present research aims to evaluate the effects of L-T4 treatment on different skeletal sites in women. Material and methods A group of 45 premenopausal (mean age: 43.62 ±6.65 years) and 180 postmenopausal (mean age: 59.51 ±7.90 years) women with SCH who were undergoing L-T4 replacement therapy for at least 6 months were compared to 58 pre- and 180 postmenopausal women with SCH (untreated) matched for age. The mean doses of L-T4 were 90.88 ±42.59 µg/day in the premenopausal women and 86.35 ±34.11 µg/day in the postmenopausal women. Bone measurements were obtained using quantitative bone ultrasound (QUS) for the phalanx, dual-energy X-ray absorptiometry (DXA) for the lumbar spine and hip, and peripheral quantitative computed tomography (pQCT) for the non-dominant distal forearm. Results No differences were observed between patients and untreated controls in these bone measurements except in the bone mineral density (BMD) of the spine (p = 0.0214) in postmenopausal women, which was greater in treated women than in untreated controls. Conclusions Our results indicate that adequate metabolic control through replacement treatment with L-T4 in pre- and postmenopausal women does not affect bone mass. PMID:26528344

  2. Investigation of using bone texture analysis on bone densitometry images

    NASA Astrophysics Data System (ADS)

    Chinander, Michael R.; Giger, Maryellen L.; Shah, Ruchi D.; Vokes, Tamara

    2002-05-01

    We previously developed bone texture analysis methods to assess bone strength on digitized radiographs. Here, we compare the analyses performed on digitized screen-film to those obtained on peripheral bone densitometry images. A leg phantom was imaged with both a PIXI (GE Medical Systems; Milwaukee, WI) bone densitometer (0.200-mm pixel size) and a screen-film system, with the films being subsequently digitized by a laser film digitizer (0.100-mm pixel size). The phantom was radiographically scanned multiple times with the densitometer at the default parameters and for increasing exposure times. Fourier-based texture features were calculated from regions of interest from images from both modalities. The bone densitometry images contained more quantum noise than the radiographs resulting in increased values for the first moment of the power spectrum texture feature (1.22 times higher than from the standard radiograph). Presence of such noise may adversely affect the texture feature's ability to distinguish between strong and weak bone. By either increasing the exposure time or averaging multiple scans in the spatial frequency domain, we showed a reduction in the effect of the quantum mottle on the first moment of the power spectrum.

  3. The role of pleiotropy and linkage in genes affecting a sexual ornament and bone allocation in the chicken.

    PubMed

    Johnsson, M; Rubin, C-J; Höglund, A; Sahlqvist, A-S; Jonsson, K B; Kerje, S; Ekwall, O; Kämpe, O; Andersson, L; Jensen, P; Wright, D

    2014-05-01

    Sexual selection and the ornaments that inform such choices have been extensively studied, particularly from a phenotypic perspective. Although more is being revealed about the genetic architecture of sexual ornaments, much still remains to be discovered. The comb of the chicken is one of the most widely recognized sexual ornaments, which has been shown to be correlated with both fecundity and bone allocation. In this study, we use a combination of multiple intercrosses between White Leghorn populations and wild-derived Red Junglefowl to, first, map quantitative trait loci (QTL) for bone allocation and, second, to identify expression QTL that correlate and colocalize with comb mass. These candidate quantitative genes were then assessed for potential pleiotropic effects on bone tissue and fecundity traits. We identify genes that correlate with both relative comb mass and bone traits suggesting a combination of both pleiotropy and linkage mediates gene regulatory variation in these traits. PMID:24655072

  4. [Bone quantitative ultrasound].

    PubMed

    Matsukawa, Mami

    2016-01-01

    The conventional ultrasonic bone densitometry system can give us information of bone as ultrasonic wave velocity and attenuation. However, the data reflect both structural and material properties of bone. In order to focus only on the bone matrix properties without the effect of bone structure, studies of microscopic Brillouin scattering technique are introduced. The wave velocity in a trabecula was anisotropic and depended on the position and structure of the cancellous bone. The glycation also affected on the wave velocities in bone. As a new bone quality, the piezoelectricity of bone is also discussed. PMID:26728531

  5. Supplementation with calcium and short-chain fructo-oligosaccharides affects markers of bone turnover but not bone mineral density in postmenopausal women.

    PubMed

    Slevin, Mary M; Allsopp, Philip J; Magee, Pamela J; Bonham, Maxine P; Naughton, Violetta R; Strain, J J; Duffy, Maresa E; Wallace, Julie M; Mc Sorley, Emeir M

    2014-03-01

    This 24-mo randomized, double-blind, controlled trial aimed to examine whether supplementation with a natural marine-derived multi-mineral supplement rich in calcium (Ca) taken alone and in conjunction with short-chain fructo-oligosaccharide (scFOSs) has a beneficial effect on bone mineral density (BMD) and bone turnover markers (BTMs) in postmenopausal women. A total of 300 non-osteoporotic postmenopausal women were randomly assigned to daily supplements of 800 mg of Ca, 800 mg of Ca with 3.6 g of scFOS (CaFOS), or 9 g of maltodextrin. BMD was measured before and after intervention along with BTMs, which were also measured at 12 mo. Intention-to-treat ANCOVA identified that the change in BMD in the Ca and CaFOS groups did not differ from that in the maltodextrin group. Secondary analysis of changes to BTMs over time identified a greater decline in osteocalcin and C-telopeptide of type I collagen (CTX) in the Ca group compared with the maltodextrin group at 12 mo. A greater decline in CTX was observed at 12 mo and a greater decline in osteocalcin was observed at 24 mo in the CaFOS group compared with the maltodextrin group. In exploratory subanalyses of each treatment group against the maltodextrin group, women classified with osteopenia and taking CaFOS had a smaller decline in total-body (P = 0.03) and spinal (P = 0.03) BMD compared with the maltodextrin group, although this effect was restricted to those with higher total-body and mean spinal BMD at baseline, respectively. Although the change in BMD observed did not differ between the groups, the greater decline in BTMs in the Ca and CaFOS groups compared with the maltodextrin group suggests a more favorable bone health profile after supplementation with Ca and CaFOS. Supplementation with CaFOS slowed the rate of total-body and spinal bone loss in postmenopausal women with osteopenia-an effect that warrants additional investigation. This trial was registered at www.controlled-trials.com as ISRCTN63118444. PMID

  6. Low to moderate alcohol consumption on serum vitamin D and other indicators of bone health in postmenopausal women in a controlled feeding study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Heavy alcohol drinking adversely affects vitamin D status and bone health. However, data from randomized, placebo-controlled trials (RCTs) on the effects of low to moderate alcohol consumption on vitamin D status and bone health in humans is unavailable. The objective of this cross-over RCT was to e...

  7. Current socio-economic measures, and not those measured during infancy, affect bone mass in poor urban South african children.

    PubMed

    Norris, Shane A; Sheppard, Zoë A; Griffiths, Paula L; Cameron, Noël; Pettifor, John M

    2008-09-01

    Understanding the impact of socio-economic status (SES) on physical development in children is important, especially in developing countries where considerable inequalities persist. This is the first study to examine the association between SES on bone development at the whole body, femoral neck, and lumbar spine in black children living in Soweto and Johannesburg, South Africa. Linear regression models were used to study associations between SES during infancy and current SES, anthropometric, and DXA-derived bone mass in 9/10-yr-old children (n = 309). Findings suggest that current SES measures, rather than SES during infancy, are stronger predictors of current whole body bone area (BA) and whole body BMC after adjusting for body size, pubertal development, physical activity, habitual dietary calcium intake, and body composition. SES had no significant effect on either hip or spine bone mass. Caregiver's marital/cohabiting status (indicator of social support) and whether there was a television in the home (indicator of greater income) at age 9/10 yr were the most important socio-economic determinants of whole body BA and BMC. SES has a significant independent effect on whole body BMC through its impact on BA. This suggests that poverty alleviation policies in South Africa could have a positive effect on bone health. PMID:18442310

  8. Genetic Analysis Identifies DDR2 as a Novel Gene Affecting Bone Mineral Density and Osteoporotic Fractures in Chinese Population

    PubMed Central

    Guo, Yan; Yang, Tie-Lin; Dong, Shan-Shan; Yan, Han; Hao, Ruo-Han; Chen, Xiao-Feng; Chen, Jia-Bin; Tian, Qing; Li, Jian; Shen, Hui; Deng, Hong-Wen

    2015-01-01

    DDR2 gene, playing an essential role in regulating osteoblast differentiation and chondrocyte maturation, may influence bone mineral density (BMD) and osteoporosis, but the genetic variations actually leading to the association remain to be elucidated. Therefore, the aim of this study was to investigate whether the genetic variants in DDR2 are associated with BMD and fracture risk. This study was performed in three samples from two ethnicities, including 1,300 Chinese Han subjects, 700 Chinese Han subjects (350 with osteoporotic hip fractures and 350 healthy controls) and 2,286 US white subjects. Twenty-eight SNPs in DDR2 were genotyped and tested for associations with hip BMD and fractures. We identified 3 SNPs in DDR2 significantly associated with hip BMD in the Chinese population after multiple testing adjustments, which were rs7521233 (P = 1.06×10−4, β: −0.018 for allele C), rs7553831 (P = 1.30×10−4, β: −0.018 for allele T), and rs6697469 (P = 1.59×10−3, β: −0.015 for allele C), separately. These three SNPs were in high linkage disequilibrium. Haplotype analyses detected two significantly associated haplotypes, including one haplotype in block 2 (P = 9.54×10−4, β: −0.016) where these three SNPs located. SNP rs6697469 was also associated with hip fractures (P = 0.043, OR: 1.42) in the Chinese population. The effect on fracture risk was consistent with its association with lower BMD. However, in the white population, we didn’t observe significant associations with hip BMD. eQTL analyses revealed that SNPs associated with BMD also affected DDR2 mRNA expression levels in Chinese. Our findings, together with the prior biological evidence, suggest that DDR2 could be a new candidate for osteoporosis in Chinese population. Our results also reveal an ethnic difference, which highlights the need for further genetic studies in each ethnic group. PMID:25658585

  9. Acute over-the-counter pharmacological intervention does not adversely affect behavioral outcome following diffuse traumatic brain injury in the mouse.

    PubMed

    Harrison, Jordan L; Rowe, Rachel K; O'Hara, Bruce F; Adelson, P David; Lifshitz, Jonathan

    2014-09-01

    Following mild traumatic brain injury (TBI), patients may self-treat symptoms of concussion, including post-traumatic headache, taking over-the-counter (OTC) analgesics. Administering one dose of OTC analgesics immediately following experimental brain injury mimics the at-home treated population of concussed patients and may accelerate the understanding of the relationship between brain injury and OTC pharmacological intervention. In the current study, we investigate the effect of acute administration of OTC analgesics on neurological function and cortical cytokine levels after experimental diffuse TBI in the mouse. Adult, male C57BL/6 mice were injured using a midline fluid percussion (mFPI) injury model of concussion (6-10 min righting reflex time for brain-injured mice). Experimental groups included mFPI paired with either ibuprofen (60 mg/kg, i.p.; n = 16), acetaminophen (40 mg/kg, i.p.; n = 9), or vehicle (15% ethanol (v/v) in 0.9% saline; n = 13) and sham injury paired OTC medicine or vehicle (n = 7-10 per group). At 24 h after injury, functional outcome was assessed using the rotarod task and a modified neurological severity score. Following behavior assessment, cortical cytokine levels were measured by multiplex ELISA at 24 h post-injury. To evaluate efficacy on acute inflammation, cortical cytokine levels were measured also at 6 h post-injury. In the diffuse brain-injured mouse, immediate pharmacological intervention did not attenuate or exacerbate TBI-induced functional deficits. Cortical cytokine levels were affected by injury, time, or their interaction. However, levels were not affected by treatment at 6 or 24 h post-injury. These data indicate that acute administration of OTC analgesics did not exacerbate or attenuate brain-injury deficits which may inform clinical recommendations for the at-home treated mildly concussed patient. PMID:24760409

  10. Is bone mineral density measurement using dual-energy X-ray absorptiometry affected by gamma rays?

    PubMed

    Xie, Liang-Jun; Li, Jian-Fang; Zeng, Feng-Wei; Jiang, Hang; Cheng, Mu-Hua; Chen, Yi

    2013-01-01

    The objective of this study was to determine whether the gamma rays emitted from the radionuclide effect bone mineral density (BMD) measurement. Nine subjects (mean age: 56 ± 17.96 yr) scheduled for bone scanning underwent BMD measurement using dual-energy X-ray absorptiometry (DXA) (Hologic/Discovery A) before and 1, 2, and 4 h after injection of technetium-99m-methylene diphosphonate (99mTc-MDP). Ten subjects (mean age: 41 ± 15.47 yr) scheduled for therapy of differentiated thyroid carcinoma with iodine-131 underwent BMD measurement before and 2 h after therapeutic radionuclide administration. All patients were given whole body BMD measurement, including head, arm, ribs, lumbar spine, pelvis, and leg sites. Besides, patients who referred to radioiodine therapy were given total hip and femoral neck BMD measurement as well. No statistically significant changes in BMD values were detected after 99mTc-MDP and iodine-131 administration for all measurement sites (p > 0.05), and individual difference of BMD before and after radionuclide imaging or therapy was less than the least significant change in lumbar spine, total hip, and femoral neck. In conclusion, BMD measurements are not influenced by the gamma rays emitted from technetium-99m and iodine-131. DXA bone densitometry may be performed simultaneously with bone scanning and radioiodine therapy. PMID:23473956

  11. Utilization of rye as energy source affects bacterial translocation, intestinal viscosity, microbiota composition, and bone mineralization in broiler chickens

    PubMed Central

    Tellez, Guillermo; Latorre, Juan D.; Kuttappan, Vivek A.; Kogut, Michael H.; Wolfenden, Amanda; Hernandez-Velasco, Xochitl; Hargis, Billy M.; Bottje, Walter G.; Bielke, Lisa R.; Faulkner, Olivia B.

    2014-01-01

    Two independent trials were conducted to evaluate the utilization of rye as energy source on bacterial translocation (BT), intestinal viscosity, gut integrity, gut microbiota composition, and bone mineralization, when compared with a traditional cereal (corn) in broiler chickens. In each experiment, day-of-hatch, broiler chickens were randomly assigned to either a corn or a rye diet (n = 20 chickens/group). At 10 d of age, in both experiments, 12 chickens/group were randomly selected, and given an oral gavage dose of fluorescein isothiocyanate dextran (FITC-d). After 2.5 h of oral gavage, blood samples were collected to determine the passage of FITC-d. The liver was collected from each bird to evaluate BT. Duodenum, ileum, and cecum gut sections were collected to evaluate intestinal viscosity and to enumerate gut microbiota. Tibias were collected for observation of bone parameters. Broilers fed with rye showed increased (p < 0.05) intestinal viscosity, BT, and serum FITC-d. Bacterial enumeration revealed that chickens fed with rye had increased the number of total lactic acid bacteria in all three sections of the gastrointestinal tract evaluated when compared to chickens fed with corn. Chickens fed with rye also had significantly higher coliforms in duodenum and ileum, whereas the total number of anaerobes increased only in duodenum. A significant reduction in bone strength and bone mineralization was observed in chickens fed with rye when compared with corn fed chickens. In conclusion, rye evoked mucosal damage in chickens that alter the intestinal viscosity, increased leakage through the intestinal tract, and altered the microbiota composition as well as bone mineralization. Studies to evaluate dietary inclusion of selected DFM candidates that produce exogenous enzymes in rye fed chickens are currently being evaluated. PMID:25309584

  12. Utilization of rye as energy source affects bacterial translocation, intestinal viscosity, microbiota composition, and bone mineralization in broiler chickens.

    PubMed

    Tellez, Guillermo; Latorre, Juan D; Kuttappan, Vivek A; Kogut, Michael H; Wolfenden, Amanda; Hernandez-Velasco, Xochitl; Hargis, Billy M; Bottje, Walter G; Bielke, Lisa R; Faulkner, Olivia B

    2014-01-01

    Two independent trials were conducted to evaluate the utilization of rye as energy source on bacterial translocation (BT), intestinal viscosity, gut integrity, gut microbiota composition, and bone mineralization, when compared with a traditional cereal (corn) in broiler chickens. In each experiment, day-of-hatch, broiler chickens were randomly assigned to either a corn or a rye diet (n = 20 chickens/group). At 10 d of age, in both experiments, 12 chickens/group were randomly selected, and given an oral gavage dose of fluorescein isothiocyanate dextran (FITC-d). After 2.5 h of oral gavage, blood samples were collected to determine the passage of FITC-d. The liver was collected from each bird to evaluate BT. Duodenum, ileum, and cecum gut sections were collected to evaluate intestinal viscosity and to enumerate gut microbiota. Tibias were collected for observation of bone parameters. Broilers fed with rye showed increased (p < 0.05) intestinal viscosity, BT, and serum FITC-d. Bacterial enumeration revealed that chickens fed with rye had increased the number of total lactic acid bacteria in all three sections of the gastrointestinal tract evaluated when compared to chickens fed with corn. Chickens fed with rye also had significantly higher coliforms in duodenum and ileum, whereas the total number of anaerobes increased only in duodenum. A significant reduction in bone strength and bone mineralization was observed in chickens fed with rye when compared with corn fed chickens. In conclusion, rye evoked mucosal damage in chickens that alter the intestinal viscosity, increased leakage through the intestinal tract, and altered the microbiota composition as well as bone mineralization. Studies to evaluate dietary inclusion of selected DFM candidates that produce exogenous enzymes in rye fed chickens are currently being evaluated. PMID:25309584

  13. Early pregnancy vitamin D status and risk for adverse maternal and infant outcomes in a bi-ethnic cohort: the Behaviors Affecting Baby and You (B.A.B.Y.) Study.

    PubMed

    Nobles, Carrie J; Markenson, Glenn; Chasan-Taber, Lisa

    2015-12-28

    Vitamin D deficiency is common during pregnancy and higher in Hispanic as compared with non-Hispanic white women. However, the association between vitamin D deficiency and adverse pregnancy outcomes remains unclear and may vary across ethnic groups, in part because of genetic variation in the metabolism of vitamin D. Few studies have included Hispanic women. Therefore, we investigated this association among 237 participants in the Behaviors Affecting Baby and You Study, a randomised trial of an exercise intervention among ethnically diverse prenatal care patients in Massachusetts. Baseline serum 25-hydroxyvitamin D (25(OH)D) was measured at 15·2 (sd 4·7) weeks' gestation. Information on adverse pregnancy outcomes was abstracted from medical records. Mean 25(OH)D was 30·4 (sd 12·0) ng/ml; 53·2 % of participants had insufficient (<30 ng/ml) and 20·7 % had deficient (<20 ng/ml) 25(OH)D levels. After adjusting for month of blood draw, gestational age at blood draw, gestational age at delivery, age, BMI and Hispanic ethnicity, women with insufficient and deficient vitamin D had infants with birth weights 139·74 (se 69·16) g (P=0·045) and 175·52 (se 89·45) g (P=0·051) lower compared with women with sufficient vitamin D levels (≥30 ng/ml). Each 1 ng/ml increase in 25(OH)D was associated with an increased risk for gestational diabetes mellitus among Hispanic women only (relative risk 1·07; 95 % CI 1·03, 1·11) in multivariable analysis. We did not observe statistically significant associations between maternal vitamin D status and other pregnancy outcomes. Our findings provide further support for an adverse impact of vitamin D deficiency on birth weight in Hispanic women. PMID:26507186

  14. Targeted overexpression of the two colony-stimulating factor-1 isoforms in osteoblasts differentially affects bone loss in ovariectomized mice

    PubMed Central

    Yao, Gang-Qing; Wu, Jian-Jun; Ovadia, Shira; Troiano, Nancy; Sun, Ben Hua; Insogna, Karl

    2009-01-01

    Colony-stimulating factor-1 (CSF1) is one of two cytokines required for normal osteoclastogenesis. There are two major isoforms of CSF1, the cell-surface or membrane-bound isoform (mCSF1) and soluble CSF1 (sCSF1). Whether these isoforms serve nonredundant functions in bone is unclear. To explore this question, we generated transgenic mice expressing human sCSF1, human mCSF1, or both (s/mCSF1) in osteoblasts using the 2.3-kb rat αI-collagen promoter. Bone density determined by peripheral quantitative computed tomography was significantly reduced in mCSF1, sCSF1, and s/mCSF1 transgenic mice compared with wild-type animals. When analyzed by sex, sCSF1, and s/mCSF1, female animals but not mCSF1 female mice were found to have greater bone loss than their male littermates (−20 vs. −9.2%; P < 0.05 for sCSF1 and −21.6 vs. −11.2% for s/mCSF1; P < 0.01). By breeding CSF1 isoform-selective transgenic mice to an op/op background, mice were generated in which a single CSF1 isoform was the only source of the cytokine (sCSF1op/op and mCSF1op/op). Unlike osteoblast-targeted overexpression of mCSF1, selective transgenic expression of sCSF1 did not completely correct the op/op phenotype in 5-mo-old animals. Interestingly, compared with sham-ovariectomized mice of the same genotype, ovariectomy in sCSF1op/op mice led to a greater loss of spinal bone mineral density (22.1%) than was seen in either mCSF1op/op mice (12.9%) or in wild-type animals (10.9%). Our findings support the conclusion that sCSF1 and mCSF1 serve nonredundant functions in bone and that sCSF1 may play a role in mediating estrogen-deficiency bone loss. PMID:19141689

  15. The factors affecting outcome after non-vascular bone grafting and internal fixation for nonunion of the scaphoid.

    PubMed

    Ramamurthy, C; Cutler, L; Nuttall, D; Simison, A J M; Trail, I A; Stanley, J K

    2007-05-01

    This study identified variables which influence the outcome of surgical management on 126 ununited scaphoid fractures managed by internal fixation and non-vascular bone grafting. The site of fracture was defined by a new method: the ratio of the length of the proximal fragment to the sum of the lengths of both fragments, calculated using specific views in the plain radiographs. Bone healing occurred in 71% (89) of cases. Only the site of nonunion (p = 1 x 10(-6)) and the delay to surgery (p = 0.001) remained significant on multivariate analysis. The effect of surgical delay on the probability of union increased as the fracture site moved proximally. A prediction model was produced by stepwise logistic regression analysis, enabling the surgeon to predict the success of surgery where the site of the nonunion and delay to surgery is known. PMID:17540748

  16. The Content of the 14 Metals in Cancellous and Cortical Bone of the Hip Joint Affected by Osteoarthritis.

    PubMed

    Zioła-Frankowska, Anetta; Kubaszewski, Łukasz; Dąbrowski, Mikołaj; Kowalski, Artur; Rogala, Piotr; Strzyżewski, Wojciech; Łabędź, Wojciech; Uklejewski, Ryszard; Novotny, Karel; Kanicky, Viktor; Frankowski, Marcin

    2015-01-01

    The aim of the study was to determine the content of particular elements Ca, Mg, P, Na, K, Zn, Cu, Fe, Mo, Cr, Ni, Ba, Sr, and Pb in the proximal femur bone tissue (cancellous and cortical bone) of 96 patients undergoing total hip replacement for osteoarthritis using ICP-AES and FAAS analytical techniques. The interdependencies among these elements and their correlations depended on factors including age, gender, place of residence, tobacco consumption, alcohol consumption, exposure to environmental pollution, physical activity, and type of degenerative change which were examined by statistical and chemometric methods. The factors that exerted the greatest influence on the elements in the femoral head and neck were tobacco smoking (higher Cr and Ni content in smokers), alcohol consumption (higher concentrations of Ni, Cu in people who consume alcohol), and gender (higher Cu, Zn, and Ni concentrations in men). The factors influencing Pb accumulation in bone tissue were tobacco, alcohol, gender, and age. In primary and secondary osteoarthritis of the hip, the content and interactions of elements are different (mainly those of Fe and Pb). There were no significant differences in the concentrations of elements in the femoral head and neck that could be attributed to residence or physical activity. PMID:26357659

  17. The Content of the 14 Metals in Cancellous and Cortical Bone of the Hip Joint Affected by Osteoarthritis

    PubMed Central

    Zioła-Frankowska, Anetta; Kubaszewski, Łukasz; Dąbrowski, Mikołaj; Kowalski, Artur; Rogala, Piotr; Strzyżewski, Wojciech; Łabędź, Wojciech; Uklejewski, Ryszard; Novotny, Karel; Kanicky, Viktor; Frankowski, Marcin

    2015-01-01

    The aim of the study was to determine the content of particular elements Ca, Mg, P, Na, K, Zn, Cu, Fe, Mo, Cr, Ni, Ba, Sr, and Pb in the proximal femur bone tissue (cancellous and cortical bone) of 96 patients undergoing total hip replacement for osteoarthritis using ICP-AES and FAAS analytical techniques. The interdependencies among these elements and their correlations depended on factors including age, gender, place of residence, tobacco consumption, alcohol consumption, exposure to environmental pollution, physical activity, and type of degenerative change which were examined by statistical and chemometric methods. The factors that exerted the greatest influence on the elements in the femoral head and neck were tobacco smoking (higher Cr and Ni content in smokers), alcohol consumption (higher concentrations of Ni, Cu in people who consume alcohol), and gender (higher Cu, Zn, and Ni concentrations in men). The factors influencing Pb accumulation in bone tissue were tobacco, alcohol, gender, and age. In primary and secondary osteoarthritis of the hip, the content and interactions of elements are different (mainly those of Fe and Pb). There were no significant differences in the concentrations of elements in the femoral head and neck that could be attributed to residence or physical activity. PMID:26357659

  18. Adverse ocular reactions to drugs.

    PubMed Central

    Spiteri, M. A.; James, D. G.

    1983-01-01

    Drugs acting on various parts of the body may also affect the eye insidiously. Increased awareness of such drug toxicity by the prescribing doctor should encourage him to consider effects on the cornea, lens, retina, optic nerve and elsewhere when checking the patient's progress. The following review concerns adverse ocular effects of systemic drug administration. PMID:6356101

  19. Sirtuin Inhibition Adversely Affects Porcine Oocyte Meiosis

    PubMed Central

    Zhang, Liang; Ma, Rujun; Hu, Jin; Ding, Xiaolin; Xu, Yinxue

    2015-01-01

    Sirtuins have been implicated in diverse biological processes, including oxidative stress, energy metabolism, cell migration, and aging. Here, we employed Sirtuin inhibitors, nicotinamide (NAM) and Sirtinol, to investigate their effects on porcine oocyte maturation respectively. The rate of polar body extrusion in porcine oocytes decreased after treatment with NAM and Sirtinol, accompanied with the failure of cumulus cell expansion. We further found that NAM and Sirtinol significantly disrupted oocyte polarity, and inhibited the formation of actin cap and cortical granule-free domain (CGFD). Moreover, the abnormal spindles and misaligned chromosomes were readily detected during porcine oocyte maturation after treatment with NAM and Sirtinol. Together, these results suggest that Sirtuins are involved in cortical polarity and spindle organization in porcine oocytes. PMID:26176547

  20. The Autophagic Process Occurs in Human Bone Metastasis and Implicates Molecular Mechanisms Differently Affected by Rab5a in the Early and Late Stages.

    PubMed

    Maroni, Paola; Bendinelli, Paola; Resnati, Massimo; Matteucci, Emanuela; Milan, Enrico; Desiderio, Maria Alfonsina

    2016-01-01

    Autophagy favours metastatic growth through fuelling energy and nutrients and resistance to anoikis, typical of disseminated-tumour cells. The autophagic process, mediated by a unique organelle, the autophagosome, which fuses with lysosomes, is divided into three steps. Several stages, especially early omegasome formation and isolation-membrane initiation, remain controversial; molecular mechanisms involve the small-GTPase Rab5a, which regulates vesicle traffic for autophagosome formation. We examined Rab5a involvement in the function of key members of ubiquitin-conjugation systems, Atg7 and LC3-lipidated, interacting with the scaffold-protein p62. Immunohistochemistry of Rab5a was performed in human specimens of bone metastasis and pair-matched breast carcinoma; the autophagic-molecular mechanisms affected by Rab5a were evaluated in human 1833 bone metastatic cells, derived from breast-carcinoma MDA-MB231 cells. To clarify the role of Rab5a, 1833 cells were transfected transiently with Rab5a-dominant negative, and/or stably with the short-hairpin RNA Atg7, were exposed to two inhibitors of autolysosome function, and LC3II and p62 expression was measured. We showed basal autophagy in bone-metastatic cells and the pivotal role of Rab5a together with Beclin 1 between the early stages, elongation of isolation membrane/closed autophagosome mediated by Atg7, and the late-degradative stages. This regulatory network might occur in bone-metastasis and in high-grade dysplastic lesions, preceding invasive-breast carcinoma and conferring phenotypic characteristics for dissemination. PMID:27023526

  1. Retinoic acid differentially affects in vitro proliferation, differentiation and mineralization of two fish bone-derived cell lines: different gene expression of nuclear receptors and ECM proteins.

    PubMed

    Fernández, Ignacio; Tiago, Daniel M; Laizé, Vincent; Leonor Cancela, M; Gisbert, Enric

    2014-03-01

    Retinoic acid (RA), the main active metabolite of vitamin A, regulates vertebrate morphogenesis through signaling pathways not yet fully understood. Such process involves the specific activation of retinoic acid and retinoid X receptors (RARs and RXRs), which are nuclear receptors of the steroid/thyroid hormone receptor superfamily. Teleost fish are suitable models to study vertebrate development, such as skeletogenesis. Cell systems capable of in vitro mineralization have been developed for several fish species and may provide new insights into the specific cellular and molecular events related to vitamin A activity in bone, complementary to in vivo studies. This work aims at investigating the in vitro effects of RA (0.5 and 12.5 μM) on proliferation, differentiation and extracellular matrix (ECM) mineralization of two gilthead seabream bone-derived cell lines (VSa13 and VSa16), and at identifying molecular targets of its action through gene expression analysis. RA induced phenotypic changes and cellular proliferation was inhibited in both cell lines in a cell type-dependent manner (36-59% in VSa13 and 17-46% in VSa16 cells). While RA stimulated mineral deposition in VSa13 cell cultures (50-62% stimulation), it inhibited the mineralization of extracellular matrix in VSa16 cells (11-57% inhibition). Expression of hormone receptor genes (rars and rxrs), and extracellular matrix-related genes such as matrix and bone Gla proteins (mgp and bglap), osteopontin (spp1) and type I collagen (col1a1) were differentially regulated upon exposure to RA in proliferating, differentiating and mineralizing cultures of VSa13 and VSa16 cells. Altogether, our results show: (i) RA affects proliferative and mineralogenic activities in two fish skeletal cell types and (ii) that during phenotype transitions, specific RA nuclear receptors and bone-related genes are differentially expressed in a cell type-dependent manner. PMID:24291400

  2. The Autophagic Process Occurs in Human Bone Metastasis and Implicates Molecular Mechanisms Differently Affected by Rab5a in the Early and Late Stages

    PubMed Central

    Maroni, Paola; Bendinelli, Paola; Resnati, Massimo; Matteucci, Emanuela; Milan, Enrico; Desiderio, Maria Alfonsina

    2016-01-01

    Autophagy favours metastatic growth through fuelling energy and nutrients and resistance to anoikis, typical of disseminated-tumour cells. The autophagic process, mediated by a unique organelle, the autophagosome, which fuses with lysosomes, is divided into three steps. Several stages, especially early omegasome formation and isolation-membrane initiation, remain controversial; molecular mechanisms involve the small-GTPase Rab5a, which regulates vesicle traffic for autophagosome formation. We examined Rab5a involvement in the function of key members of ubiquitin-conjugation systems, Atg7 and LC3-lipidated, interacting with the scaffold-protein p62. Immunohistochemistry of Rab5a was performed in human specimens of bone metastasis and pair-matched breast carcinoma; the autophagic-molecular mechanisms affected by Rab5a were evaluated in human 1833 bone metastatic cells, derived from breast-carcinoma MDA-MB231 cells. To clarify the role of Rab5a, 1833 cells were transfected transiently with Rab5a-dominant negative, and/or stably with the short-hairpin RNA Atg7, were exposed to two inhibitors of autolysosome function, and LC3II and p62 expression was measured. We showed basal autophagy in bone-metastatic cells and the pivotal role of Rab5a together with Beclin 1 between the early stages, elongation of isolation membrane/closed autophagosome mediated by Atg7, and the late-degradative stages. This regulatory network might occur in bone-metastasis and in high-grade dysplastic lesions, preceding invasive-breast carcinoma and conferring phenotypic characteristics for dissemination. PMID:27023526

  3. Peripheral bone mass is not affected by winter vitamin D deficiency in children and young adults from Ushuaia.

    PubMed

    Oliveri, M B; Wittich, A; Mautalen, C; Chaperon, A; Kizlansky, A

    2000-09-01

    Low vitamin D levels in elderly people are associated with reduced bone mass, secondary hyperparathyroidism, and increased fracture risk. Its effect on the growing skeleton is not well known. The aim of this study was to evaluate the possible influence of chronic winter vitamin D deficiency and higher winter parathyroid hormone (PTH) levels on bone mass in prepubertal children and young adults. The study was carried out in male and female Caucasian subjects. A total of 163 prepubertal children (X age +/- 1 SD: 8.9 +/- 0.7 years) and 234 young adults (22.9 +/- 3.6 years) who had never received vitamin D supplementation were recruited from two areas in Argentina: (1)Ushuaia (55 degrees South latitude), where the population is known to have low winter 25OHD levels and higher levels of PTH in winter than in summer, and (2)Buenos Aires (34 degrees S), where ultraviolet (UV) radiation and vitamin D nutritional status in the population are adequate all year round. Bone mineral content (BMC) and bone mineral density (BMD) of the ultradistal and distal radius were measured in the young adults. Only distal radius measurements were taken in the children. Similar results were obtained in age-sex matched groups from both areas. The only results showing significant difference corresponded to comparison among the Ushuaian women: those whose calcium (Ca) intake was below 800 mg/day presented lower BMD and BMC values than those whose Ca intake was above that level (0.469 +/- 0.046 versus 0.498 +/- 0.041 g/cm(2), P < 0.02; 3.131 +/- 0.367 versus 3.339 +/- 0.386 g, P < 0.05, respectively). In conclusion, peripheral BMD and BMC were similar in children and young adults from Ushuaia and Buenos Aires in spite of the previously documented difference between both areas regarding UV radiation and winter vitamin D status. BMD of axial skeletal areas as well the concomitant effect of a low Ca diet and vitamin D deficiency on the growing skeleton should be studied further. PMID:10954776

  4. Genome-Wide Association Study Using Extreme Truncate Selection Identifies Novel Genes Affecting Bone Mineral Density and Fracture Risk

    PubMed Central

    Duncan, Emma L.; Danoy, Patrick; Kemp, John P.; Leo, Paul J.; McCloskey, Eugene; Nicholson, Geoffrey C.; Eastell, Richard; Prince, Richard L.; Eisman, John A.; Jones, Graeme; Sambrook, Philip N.; Reid, Ian R.; Dennison, Elaine M.; Wark, John; Richards, J. Brent; Uitterlinden, Andre G.; Spector, Tim D.; Esapa, Chris; Cox, Roger D.; Brown, Steve D. M.; Thakker, Rajesh V.; Addison, Kathryn A.; Bradbury, Linda A.; Center, Jacqueline R.; Cooper, Cyrus; Cremin, Catherine; Estrada, Karol; Felsenberg, Dieter; Glüer, Claus-C.; Hadler, Johanna; Henry, Margaret J.; Hofman, Albert; Kotowicz, Mark A.; Makovey, Joanna; Nguyen, Sing C.; Nguyen, Tuan V.; Pasco, Julie A.; Pryce, Karena; Reid, David M.; Rivadeneira, Fernando; Roux, Christian; Stefansson, Kari; Styrkarsdottir, Unnur; Thorleifsson, Gudmar; Tichawangana, Rumbidzai; Evans, David M.; Brown, Matthew A.

    2011-01-01

    Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55–85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or −4.0 to −1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD–associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies. PMID:21533022

  5. Vaccine Adverse Events

    MedlinePlus

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability ( ... Center for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More ...

  6. How does the supernatant of Lactobacillus acidophilus affect the proliferation and differentiation activities of rat bone marrow-derived stromal cells?

    PubMed

    Samadikuchaksaraei, A; Gholipourmalekabadi, M; Saberian, M; Abdollahpour Alitappeh, M; Shahidi Delshad, E

    2016-01-01

    Low proliferation rate and unwanted differentiation of bone marrow-derived stromal cells (rBMSCs) during the frequent passages have limited the use of such cells in clinical cell therapy. Recently, the researchers have focused on the effects of the components produced by some bacteria on proliferation of the stem cells. In this study, we discussed the possible effects of the Lactobacillus acidophilus supernatant on proliferation and differentiation of the rBMSCs. For this aim, the cells were isolated from rat bone marrow, characterized by culturing on tissue specific differentiation media and stained. The cells (passage two) were treated with different concentrations of the L. acidophilus supernatant (0, 0.1, 0.3, 0.9, 3, 9 and 30 &mgr;l/ml) for 14 days. The proliferation and differentiation capacity of the cells were then determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT assay) and tissue specific staining. The results showed a positive effect of the supernatant on the cell proliferation in 3 and 9 &mgr;l/ml concentrations, while did not affect the differentiation capacity of the rBMSCs. The current study strongly suggests the L. acidophilus supernatant as an alternative material that could be added to the media with aim of improvement in the proliferation rate of the rBMSCs without affecting their differentiation capacity. PMID:27609467

  7. Early tissue responses to zoledronate, locally delivered by bone screw, into a compromised cancellous bone site: a pilot study

    PubMed Central

    2014-01-01

    Background In fracture treatment, adequate fixation of implants is crucial to long-term clinical performance. Bisphosphonates (BP), potent inhibitors of osteoclastic bone resorption, are known to increase peri-implant bone mass and accelerate primary fixation. However, adverse effects are associated with systemic use of BPs. Thus, Zoledronic acid (ZOL) a potent BP was loaded on bone screws and evaluated in a local delivery model. Whilst mid- to long-term effects are already reported, early cellular events occurring at the implant/bone interface are not well described. The present study investigated early tissue responses to ZOL locally delivered, by bone screw, into a compromised cancellous bone site. Methods ZOL was immobilized on fibrinogen coated titanium screws. Using a bilateral approach, ZOL loaded test and non-loaded control screws were implanted into femoral condyle bone defects, created by an overdrilling technique. Histological analyses of the local tissue effects such as new bone formation and osteointegration were performed at days 1, 5 and 10. Results Histological evaluation of the five day ZOL group, demonstrated a higher osseous differentiation trend. At ten days an early influx of mesenchymal and osteoprogenitor cells was seen and a higher level of cellular proliferation and differentiation (p < 5%). In the ZOL group bone-to-screw contact and bone volume values within the defect tended to increase. Local drug release did not induce any adverse cellular effects. Conclusion This study indicates that local ZOL delivery into a compromised cancellous bone site actively supports peri-implant osteogenesis, positively affecting mesenchymal cells, at earlier time points than previously reported in the literature. PMID:24656151

  8. Organic trace minerals and 25-hydroxycholecalciferol affect performance characteristics, leg abnormalities, and biomechanical properties of leg bones of turkeys.

    PubMed

    Ferket, P R; Oviedo-Rondón, E O; Mente, P L; Bohórquez, D V; Santos, A A; Grimes, J L; Richards, J D; Dibner, J J; Felts, V

    2009-01-01

    Leg problems and resulting mortality can exceed 1% per week in turkey toms starting at approximately 15 wk of age. Dietary supplementation of organic trace minerals (MIN) and 25-hydroxycholecalciferol (HyD) may improve performance, decrease incidence of leg abnormalities, and increase bone strength. Nicholas 85X700 toms were assigned to 4 treatments consisting of a factorial arrangement of 2 concentrations of MIN (0 and 0.1% of Mintrex P(Se), which adds 40, 40, 20, and 0.3 mg/kg of Zn, Mn, Cu, and Se, respectively) and 2 concentrations of HyD (0 and 92 microg/kg of HyD). Diets were formulated to be equal in nutrient content and fed ad libitum as 8 feed phases. Feed intake and BW were measured at 6, 12, 15, 17, and 20 wk of age. Valgus, varus, and shaky leg defects were determined at 12, 15, 17, and 20 wk of age. Tibia and femur biomechanical properties were evaluated by torsion and bending tests at 17 wk of age. There were no treatment effects on BW. Only MIN significantly improved feed conversion ratio through to 20 wk of age. Cumulative mortality at 3 wk of age was greater among the MIN birds, but it was lower by 20 wk (P = 0.085). The MIN decreased the incidence of varus defects at 17 wk of age; shaky leg at 12, 15, and 17 wk of age; and valgus defects at 15, 17, and 20 wk of age. There were no MIN x HyD interaction effects on individual gait problems. Maximum load and the bending stress required for tibias to break in a 4-point assay were increased with MIN supplementation, especially when HyD was also added. Maximum shear stress at failure of femoral bones in a torsion assay was increased by supplementation with both MIN and HyD together. Dietary supplementation of MIN and HyD may improve biomechanical properties of bones. Dietary MIN supplementation may improve feed conversion of turkeys, likely by decreasing leg problems. PMID:19096066

  9. Biologics in dermatology: adverse effects.

    PubMed

    Sehgal, Virendra N; Pandhi, Deepika; Khurana, Ananta

    2015-12-01

    Biologics are a group of drugs that precisely affect certain specific steps in the immune response and are an extremely useful group when used in an appropriate setting. However, their use can often be a double-edged sword. Careful patient selection and thorough knowledge of adverse effects is a key to their successful use in various disorders. The initial enthusiasm has gradually given way to a more cautious approach wherein a balance is sought between clinical usefulness and expected side effects. The adverse effects of the biologics most commonly used in dermatology have been carefully listed for ready reference. The plausible causes of the adverse reactions are succinctly outlined along with their incriminating factor(s). Besides, in brief, the attention has been focused on their management. The content should provide an essential didactic content for educating the practitioner. PMID:26147909

  10. Overexpression of the Circadian Clock Gene Rev-erbα Affects Murine Bone Mesenchymal Stem Cell Proliferation and Osteogenesis

    PubMed Central

    He, Yao; Lin, Fuwei; Chen, Yaqun; Tan, Zhen; Bai, Ding

    2015-01-01

    Bone mesenchymal stem cell (BMSC) age-related changes include decreased osteogenesis and increased adipogenesis. Rev-erbα and the Wnt/β-catenin signaling pathway were known to play important roles in BMSC aging. In this study, we have aimed to elucidate whether Rev-erbα and Wnt/β-catenin signaling interact during BMSC proliferation and osteogenesis. Our results showed that Rev-erbα expression gradually dropped during BMSC osteogenesis, and overexpression of Rev-erbα in BMSCs inhibited cell proliferation and osteogenesis. The inhibition of cell proliferation induced by Rev-erbα overexpression was partially reversed when Wnt/β-catenin signaling was activated. These results suggested that Rev-erbα could promote BMSC aging and may be the negative regulator during the late stage of osteogenesis. The clock gene Rev-erbα and Wnt/β-catenin signaling interact in the regulation of cell proliferation. PMID:25539035

  11. The steady-state serum concentration of genistein aglycone is affected by formulation: a bioequivalence study of bone products.

    PubMed

    Bitto, Alessandra; Burnett, Bruce P; Polito, Francesca; Russo, Silvia; D'Anna, Rosario; Pillai, Lakshmi; Squadrito, Francesco; Altavilla, Domenica; Levy, Robert M

    2013-01-01

    An FDA-regulated, prescription medical food (Fosteum; 27 mg natural genistein, 200 IU cholecalciferol, 20 mg citrated zinc bisglycinate (4 mg elemental zinc) per capsule) and an over-the-counter (OTC) supplement (Citracal Plus Bone Density Builder; 27 mg synthetic genistein, 600 mg elemental calcium (calcium citrate), 400 IU vitamin D3, 50 mg magnesium, 7.5 mg zinc, 1 mg copper, 75 μ g molybdenum, 250 μ g boron per two tablets) were compared to a clinically proven bone formulation (27 mg natural genistein, 400 IU cholecalciferol, 500 mg elemental calcium (calcium carbonate) per tablet; the Squadrito formulation) in an 8-day steady-state pharmacokinetic (PK) study of healthy postmenopausal women (n = 30) randomized to receive 54 mg of genistein per day. Trough serum samples were obtained before the final dose on the morning of the ninth day followed by sampling at 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hrs. Total serum genistein, after β -glucuronidase/sulfatase digestion, was measured by time-resolved fluorometric assay. Maximal time (Tmax), concentration (Cmax), half-life (T1/2), and area under the curve (AUC) were determined for genistein in each formulation. Fosteum and the Squadrito study formulation were equivalent for genistein Tmax (2 hrs), Cmax (0.7 μM), T1/2 (18 ± 6.9 versus 21 ± 4.9 hrs), and AUC (9221 ± 413 versus 9818 ± 1370 ng·hr/mL). The OTC supplement's synthetically derived genistein, however, showed altered Tmax (6 hrs), Cmax (0.57 μ M), T1/2 (8.3 ± 1.9 hrs), and AUC (6474 ± 287 ng·hr/mL). Differences in uptake may be due to multiple ingredients in the OTC supplement which interfere with genistein absorption. PMID:23484100

  12. Modulation of Vitamin D Status and Dietary Calcium Affects Bone Mineral Density and Mineral Metabolism in Göttingen Minipigs

    PubMed Central

    Scholz-Ahrens, Katharina E.; Glüer, Claus-Christian; Bronner, Felix; Delling, Günter; Açil, Yahya; Hahne, Hans-Jürgen; Hassenpflug, Joachim; Timm, Wolfram; Schrezenmeir, Jürgen

    2013-01-01

    Calcium and vitamin D deficiency impairs bone health and may cause rickets in children and osteomalacia in adults. Large animal models are useful to study experimental osteopathies and associated metabolic changes. We intended to modulate vitamin D status and induce nutritional osteomalacia in minipigs. The control group (n = 9) was fed a semisynthetic reference diet with 6 g calcium and 6,500 IU vitamin D3/kg and the experimental group (n = 10) the same diet but with only 2 g calcium/kg and without vitamin D. After 15 months, the deficient animals were in negative calcium balance, having lost bone mineral density significantly (means ± SEM) with −51.2 ± 14.7 mg/cm3 in contrast to controls (−2.3 ± 11.8 mg/cm3), whose calcium balance remained positive. Their osteoid surface was significantly higher, typical of osteomalacia. Their plasma 25(OH)D dropped significantly from 60.1 ± 11.4 nmol/L to 15.3 ± 3.4 nmol/L within 10 months, whereas that of the control group on the reference diet rose. Urinary phosphorus excretion and plasma 1,25-dihydroxyvitamin D concentrations were significantly higher and final plasma calcium significantly lower than in controls. We conclude that the minipig is a promising large animal model to induce nutritional osteomalacia and to study the time course of hypovitaminosis D and associated functional effects. PMID:24062955

  13. Exercise frequency and bone mineral density development in exercising postmenopausal osteopenic women. Is there a critical dose of exercise for affecting bone? Results of the Erlangen Fitness and Osteoporosis Prevention Study.

    PubMed

    Kemmler, Wolfgang; von Stengel, Simon; Kohl, Matthias

    2016-08-01

    Due to older people's low sports participation rates, exercise frequency may be the most critical component for designing exercise protocols that address bone. The aims of the present article were to determine the independent effect of exercise frequency (ExFreq) and its corresponding changes on bone mineral density (BMD) and to identify the minimum effective dose that just relevantly affects bone. Based on the 16-year follow-up of the intense, consistently supervised Erlangen Fitness and Osteoporosis Prevention-Study, ExFreq was retrospectively determined in the exercise-group of 55 initially early-postmenopausal females with osteopenia. Linear mixed-effect regression analysis was conducted to determine the independent effect of ExFreq on BMD changes at lumbar spine and total hip. Minimum effective dose of ExFreq based on BMD changes less than the 90% quantile of the sedentary control-group (n=43). Cut-offs were determined after 4, 8, 12 and 16years using bootstrap with 5000 replications. After 16years, average ExFreq ranged between 1.02 and 2.96sessions/week (2.28±0.40sessions/week). ExFreq has an independent effect on LS-BMD (p<.001) and hip-BMD (p=.005) changes. Bootstrap analysis detected a minimum effective dose at about 2sessions/week/16years (cut-off LS-BMD: 2.11, 95% CI: 2.06-2.12; total hip-BMD: 2.22, 95% CI: 2.00-2.78sessions/week/16years). In summary, the minimum effective dose of exercise frequency that relevantly addresses BMD is quite high, at least compared with the low sport participation rate of older adults. This result might not be generalizable across all exercise types, protocols and cohorts, but it does indicate at least that even when applying high impact/high intensity programs, exercise frequency and its maintenance play a key role in bone adaptation. PMID:27108341

  14. Urinary Calcium and Oxalate Excretion in Healthy Adult Cats Are Not Affected by Increasing Dietary Levels of Bone Meal in a Canned Diet

    PubMed Central

    Passlack, Nadine; Zentek, Jürgen

    2013-01-01

    This study aimed to investigate the impact of dietary calcium (Ca) and phosphorus (P), derived from bone meal, on the feline urine composition and the urinary pH, allowing a risk assessment for the formation of calcium oxalate (CaOx) uroliths in cats. Eight healthy adult cats received 3 canned diets, containing 12.2 (A), 18.5 (B) and 27.0 g Ca/kg dry matter (C) and 16.1 (A), 17.6 (B) and 21.1 g P/kg dry matter (C). Each diet was fed over 17 days. After a 7 dayś adaptation period, urine and faeces were collected over 2×4 days (with a two-day rest between), and blood samples were taken. Urinary and faecal minerals, urinary oxalate (Ox), the urinary pH and the concentrations of serum Ca, phosphate and parathyroid hormone (PTH) were analyzed. Moreover, the urine was microscopically examined for CaOx uroliths. The results demonstrated that increasing levels of dietary Ca led to decreased serum PTH and Ca and increased faecal Ca and P concentrations, but did not affect the urinary Ca or Ox concentrations or the urinary fasting pH. The urinary postprandial pH slightly increased when the diet C was compared to the diet B. No CaOx crystals were detected in the urine of the cats. In conclusion, urinary Ca excretion in cats seems to be widely independent of the dietary Ca levels when Ca is added as bone meal to a typical canned diet, implicating that raw materials with higher contents of bones are of subordinate importance as risk factors for the formation of urinary CaOx crystals. PMID:23940588

  15. Nicotine Affects Bone Resorption and Suppresses the Expression of Cathepsin K, MMP-9 and Vacuolar-Type H+-ATPase d2 and Actin Organization in Osteoclasts

    PubMed Central

    Tanaka, Hideki; Tanabe, Natsuko; Kawato, Takayuki; Nakai, Kumiko; Kariya, Taro; Matsumoto, Sakurako; Zhao, Ning; Motohashi, Masafumi; Maeno, Masao

    2013-01-01

    Tobacco smoking is an important risk factor for the development of several cancers, osteoporosis, and inflammatory diseases such as periodontitis. Nicotine is one of the major components of tobacco. In previous study, we showed that nicotine inhibits mineralized nodule formation by osteoblasts, and the culture medium from osteoblasts containing nicotine and lipopolysaccharide increases osteoclast differentiation. However, the direct effect of nicotine on the differentiation and function of osteoclasts is poorly understood. Thus, we examined the direct effects of nicotine on the expression of nicotine receptors and bone resorption-related enzymes, mineral resorption, actin organization, and bone resorption using RAW264.7 cells and bone marrow cells as osteoclast precursors. Cells were cultured with 10−5, 10−4, or 10−3 M nicotine and/or 50 µM α-bungarotoxin (btx), an 7 nicotine receptor antagonist, in differentiation medium containing the soluble RANKL for up 7 days. 1–5, 7, 9, and 10 nicotine receptors were expressed on RAW264.7 cells. The expression of 7 nicotine receptor was increased by the addition of nicotine. Nicotine suppressed the number of tartrate-resistant acid phosphatase positive multinuclear osteoclasts with large nuclei(≥10 nuclei), and decreased the planar area of each cell. Nicotine decreased expression of cathepsin K, MMP-9, and V-ATPase d2. Btx inhibited nicotine effects. Nicotine increased CA II expression although decreased the expression of V-ATPase d2 and the distribution of F-actin. Nicotine suppressed the planar area of resorption pit by osteoclasts, but did not affect mineral resorption. These results suggest that nicotine increased the number of osteoclasts with small nuclei, but suppressed the number of osteoclasts with large nuclei. Moreover, nicotine reduced the planar area of resorption pit by suppressing the number of osteoclasts with large nuclei, V-ATPase d2, cathepsin K and MMP-9 expression and actin organization. PMID

  16. Bone Grafts

    MedlinePlus

    A bone graft transplants bone tissue. Surgeons use bone grafts to repair and rebuild diseased bones in your hips, knees, spine, and sometimes other bones and joints. Grafts can also repair bone loss caused by some ...

  17. Bone tumor

    MedlinePlus

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  18. The Steady-State Serum Concentration of Genistein Aglycone Is Affected by Formulation: A Bioequivalence Study of Bone Products

    PubMed Central

    Bitto, Alessandra; Burnett, Bruce P.; Polito, Francesca; Russo, Silvia; D'Anna, Rosario; Pillai, Lakshmi; Squadrito, Francesco; Altavilla, Domenica; Levy, Robert M.

    2013-01-01

    An FDA-regulated, prescription medical food (Fosteum; 27 mg natural genistein, 200 IU cholecalciferol, 20 mg citrated zinc bisglycinate (4 mg elemental zinc) per capsule) and an over-the-counter (OTC) supplement (Citracal Plus Bone Density Builder; 27 mg synthetic genistein, 600 mg elemental calcium (calcium citrate), 400 IU vitamin D3, 50 mg magnesium, 7.5 mg zinc, 1 mg copper, 75 μg molybdenum, 250 μg boron per two tablets) were compared to a clinically proven bone formulation (27 mg natural genistein, 400 IU cholecalciferol, 500 mg elemental calcium (calcium carbonate) per tablet; the Squadrito formulation) in an 8-day steady-state pharmacokinetic (PK) study of healthy postmenopausal women (n = 30) randomized to receive 54 mg of genistein per day. Trough serum samples were obtained before the final dose on the morning of the ninth day followed by sampling at 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hrs. Total serum genistein, after β-glucuronidase/sulfatase digestion, was measured by time-resolved fluorometric assay. Maximal time (Tmax), concentration (Cmax), half-life (T1/2), and area under the curve (AUC) were determined for genistein in each formulation. Fosteum and the Squadrito study formulation were equivalent for genistein Tmax (2 hrs), Cmax (0.7 μM), T1/2 (18 ± 6.9 versus 21 ± 4.9 hrs), and AUC (9221 ± 413 versus 9818 ± 1370 ng·hr/mL). The OTC supplement's synthetically derived genistein, however, showed altered Tmax (6 hrs), Cmax (0.57 μM), T1/2 (8.3 ± 1.9 hrs), and AUC (6474 ± 287 ng·hr/mL). Differences in uptake may be due to multiple ingredients in the OTC supplement which interfere with genistein absorption. PMID:23484100

  19. The Competitive Interplay between Allosteric HIV-1 Integrase Inhibitor BI/D and LEDGF/p75 during the Early Stage of HIV-1 Replication Adversely Affects Inhibitor Potency.

    PubMed

    Feng, Lei; Dharmarajan, Venkatasubramanian; Serrao, Erik; Hoyte, Ashley; Larue, Ross C; Slaughter, Alison; Sharma, Amit; Plumb, Matthew R; Kessl, Jacques J; Fuchs, James R; Bushman, Frederic D; Engelman, Alan N; Griffin, Patrick R; Kvaratskhelia, Mamuka

    2016-05-20

    Allosteric HIV-1 integrase inhibitors (ALLINIs) have recently emerged as a promising class of antiretroviral agents and are currently in clinical trials. In infected cells, ALLINIs potently inhibit viral replication by impairing virus particle maturation but surprisingly exhibit a reduced EC50 for inhibiting HIV-1 integration in target cells. To better understand the reduced antiviral activity of ALLINIs during the early stage of HIV-1 replication, we investigated the competitive interplay between a potent representative ALLINI, BI/D, and LEDGF/p75 with HIV-1 integrase. While the principal binding sites of BI/D and LEDGF/p75 overlap at the integrase catalytic core domain dimer interface, we show that the inhibitor and the cellular cofactor induce markedly different multimerization patterns of full-length integrase. LEDGF/p75 stabilizes an integrase tetramer through the additional interactions with the integrase N-terminal domain, whereas BI/D induces protein-protein interactions in C-terminal segments that lead to aberrant, higher-order integrase multimerization. We demonstrate that LEDGF/p75 binds HIV-1 integrase with significantly higher affinity than BI/D and that the cellular protein is able to reverse the inhibitor induced aberrant, higher-order integrase multimerization in a dose-dependent manner in vitro. Consistent with these observations, alterations of the cellular levels of LEDGF/p75 markedly affected BI/D EC50 values during the early steps of HIV-1 replication. Furthermore, genome-wide sequencing of HIV-1 integration sites in infected cells demonstrate that LEDGF/p75-dependent integration site selection is adversely affected by BI/D treatment. Taken together, our studies elucidate structural and mechanistic details of the interplay between LEDGF/p75 and BI/D during the early stage of HIV-1 replication. PMID:26910179

  20. Basketball Affects Bone Mineral Density Accrual in Boys More Than Swimming and Other Impact Sports: 9-mo Follow-Up.

    PubMed

    Agostinete, Ricardo R; Lynch, Kyle R; Gobbo, Luís A; Lima, Manoel Carlos Spiguel; Ito, Igor H; Luiz-de-Marco, Rafael; Rodrigues-Junior, Mario A; Fernandes, Romulo A

    2016-01-01

    The objective of this study was to analyze the effect of different sports on bone mineral density (BMD) accrual among male adolescents during a 9-mo follow-up. The sample was composed of 82 boys (control [n = 13], basketball [n = 14], karate [n = 9], soccer [n = 18], judo [n = 12], and swimming [n = 16]) who were followed up for 9 mo (from October 2013 to August 2014). BMD (gram per square centimeter) was assessed at baseline and follow-up using a dual-energy X-ray absorptiometry scanner, whereas somatic maturation was estimated through the use of the peak height velocity. Vitamin D consumption was assessed by questionnaire. After 9 mo of follow-up, all groups (including the control group) presented significant BMD accrual (overall sample: 4.5% in the whole body). On the other hand, the basketball group presented higher BMD accrual in the upper limbs (17.6%) than the control group (7.2%). A similar difference was observed in whole-body BMD (control group: 4.1% vs basketball group: 7.1%). The basketball group had significantly higher BMD gains than the control group and other sports groups. PMID:27174316

  1. [Bone and Nutrition. Bone and phosphorus intake].

    PubMed

    Arai, Hidekazu; Sakuma, Masae

    2015-07-01

    Phosphorus is necessary for bone mineralization. Although adequate phosphorus intake is essential for skeletal mineralization, it is reported that excessive phosphorus intake can induce deleterious effect on bone. Recently, since the Japanese diet has been westernized, phosphorus intake by the meat and dairy products has increased. Furthermore, along with the development of processed foods, excessive intake of inorganic phosphorus from food additives has become a problem. An adverse effect on parathyroid hormone (PTH) secretion from high phosphorus intake was seen only when calcium intake was inadequate. Dietary calcium to phosphorus ratio can be considered as one of the indicators that can predict the health of the bone. PMID:26119308

  2. Relationships existing between the serum cytokine levels and bone mineral density in women in the premenopausal period affected by Graves' disease with subclinical hyperthyroidism.

    PubMed

    Ugur-Altun, Betül; Altun, Armagan; Arikan, Ender; Guldiken, Sibel; Tugrul, Armagan

    2003-11-01

    We examined the relationships existing between serum cytokine levels and bone mineral density (BMD) in women of premenopausal age affected by Graves' disease with subclinical hyperthyroidism. The study population consisted of 21 women with untreated hyperthyroid Graves' disease (group H) (age, 36 +/- 2 years), eight women with untreated subclinical hyperthyroid status (group SH) (age, 33 +/- 5 years) and 10 healthy women (group N) (age, 35 +/- 3 years). The following measurements were made in all patients: free T4 (fT4), free T3 (fT3), thyroid stimulating hormone (TSH), TSH receptor antibody (TRab), anti-thyroid peroxidase antibody (anti-TPO), anti-thyroglobulin antibody (anti-Tg), interleukin-2 receptor (IL-2r), interleukin-4 (IL-4), interleukin-8 (IL-8) and interleukin-13 (IL-13). IL-2r and IL-8 levels significantly increased in group H compared with group SH (p < 0.01 and p = 0.05, respectively) and group N (p < 0.001 and p = 0.02, respectively). IL-4 and IL-13 levels tended to be lower in groups H and SH compared with group N, although this difference did not reach statistical significance. Bone mineral density was significantly reduced in only two areas of the femur in group H compared with group N. There was no difference in BMD between groups SH and N. There was no correlation between thyroid hormones, serum cytokine levels and BMD in either group. In conclusion, these results suggest that there were no relationships existing between the serum level of these cytokines and BMD in women of premenopausal age affected by Graves' disease with subclinical hyperthyroidism. PMID:14682468

  3. Adverse antibiotic drug interactions.

    PubMed

    Bint, A J; Burtt, I

    1980-07-01

    There is enormous potential for drug interactions in patients who, today, often receive many drugs. Antibiotics are prominent amongst the groups of drugs commonly prescribed. Many interactions take place at the absorption stage. Antacids and antidiarrhoeal preparations, in particular, can delay and reduce the absorption of antibiotics such as tetracyclines and clindamycin, by combining with them in the gastrointestinal tract to form chelates or complexes. Other drugs can affect gastric motility, which in turn often controls the rate at which antibiotics are absorbed. Some broad spectrum antibiotics can alter the bacterial flora of the gut which may be related to malabsorption states. The potentiation of toxic side effects of one drug by another is a common type of interaction. Antibiotics which are implicated in this type of interaction are those which themselves possess some toxicity such as aminoglycosides, some cephalosporins, tetracyclines and colistin. Some of the most important adverse interactions with antibiotics are those which involve other drugs which have a low toxicity/efficacy ratio. These include anticoagulants such as warfarin, anticonvulsants such as phenytoin and phenobarbitone and oral antidiabetic drugs like tolbutamide. Risk of interaction arises when the metabolism of these drugs is inhibited by liver microsomal enzyme inhibitors such as some sulphonamides and chloramphenicol, or is enhanced by enzyme inducers such as rifampicin. PMID:6995091

  4. Role of Corticosteroids in Bone Loss During Space Flight

    NASA Technical Reports Server (NTRS)

    Wronski, Thomas J.; Halloran, Bernard P.; Miller, Scott C.

    1998-01-01

    The primary objective of this research project is to test the hypothesis that corticosteroids contribute to the adverse skeletal effects of space flight. To achieve this objective, serum corticosteroids, which are known to increase during space flight, must be maintained at normal physiologic levels in flight rats by a combination of adrenalectomy and corticosteroid supplementation via implanted hormone pellets. Bone analyses in these animals will then be compared to those of intact flight rats that, based on past experience, will undergo corticosteroid excess and bone loss during space flight. The results will reveal whether maintaining serum corticosteroids at physiologic levels in flight rats affects the skeletal abnormalities that normally develop during space flight. A positive response to this question would indicate that the bone loss and decreased bone formation associated with space flight are mediated, at least in part, by corticosteroid excess.

  5. Cigarette smoking and bone healing: implications in foot and ankle surgery.

    PubMed

    Haverstock, B D; Mandracchia, V J

    1998-01-01

    Despite the known health risks associated with cigarettes, millions of Americans continue to smoke. Much has been reported on the adverse effects of cigarette smoke on wound healing. Recent experimental work and clinical observation have demonstrated the risk of impaired bone healing associated with cigarette smoking. The authors review the biological aspects of bone healing and analyze how the chemical components of cigarette smoke affect the bone healing process. Laboratory and clinical data are also reviewed. Cessation of cigarette smoking before foot and ankle surgery is recommended by the authors. PMID:9470121

  6. Bisphosphonates and bone quality

    PubMed Central

    Pazianas, Michael; van der Geest, Stefan; Miller, Paul

    2014-01-01

    Bisphosphonates (BPs) are bone-avid compounds used as first-line medications for the prevention and treatment of osteoporosis. They are also used in other skeletal pathologies such as Paget's and metastatic bone disease. They effectively reduce osteoclast viability and also activity in the resorptive phase of bone remodelling and help preserve bone micro-architecture, both major determinants of bone strength and ultimately of the susceptibility to fractures. The chemically distinctive structure of each BP used in the clinic determines their unique affinity, distribution/penetration throughout the bone and their individual effects on bone geometry, micro-architecture and composition or what we call ‘bone quality'. BPs have no clinically significant anabolic effects. This review will touch upon some of the components of bone quality that could be affected by the administration of BPs. PMID:24876930

  7. Urbanicity, social adversity and psychosis

    PubMed Central

    Heinz, Andreas; Deserno, Lorenz; Reininghaus, Ulrich

    2013-01-01

    In recent years, there has been increasing interest in research on geographical variation in the incidence of schizophrenia and other psychoses. In this paper, we review the evidence on variation in incidence of schizophrenia and other psychoses in terms of place, as well as the individual- and area-level factors that account for this variation. We further review findings on potential mechanisms that link adverse urban environment and psychosis. There is evidence from earlier and more recent studies that urbanicity is associated with an increased incidence of schizophrenia and non-affective psychosis. In addition, considerable variation in incidence across neighbourhoods has been observed for these disorders. Findings suggest it is unlikely that social drift alone can fully account for geographical variation in incidence. Evidence further suggests that the impact of adverse social contexts – indexed by area-level exposures such as population density, social fragmentation and deprivation – on risk of psychosis is explained (confounding) or modified (interaction) by environmental exposures at the individual level (i.e., cannabis use, social adversity, exclusion and discrimination). On a neurobiological level, several studies suggest a close link between social adversity, isolation and stress on the one hand, and monoamine dysfunction on the other, which resembles findings in schizophrenia patients. However, studies directly assessing correlations between urban stress or discrimination and neurobiological alterations in schizophrenia are lacking to date. PMID:24096775

  8. Bone Diseases

    MedlinePlus

    ... avoid smoking and drinking too much alcohol. Bone diseases can make bones easy to break. Different kinds ... break Osteogenesis imperfecta makes your bones brittle Paget's disease of bone makes them weak Bones can also ...

  9. Calcium sources and their interaction with the different levels of non-phytate phosphorus affect performance and bone mineralization in broiler chickens.

    PubMed

    Hamdi, M; Solà-Oriol, D; Davin, R; Perez, J F

    2015-09-01

    An experiment was conducted to evaluate the influence of different Ca sources (limestone, Ca chloride, and Lipocal, a fat-encapsulated tricalcium phosphate, TCP) in conjunction with 4 dietary levels of non-phytate P (NPP) on performance, ileal digestibility of Ca and P, and bone mineralization in broiler chickens. Calcium sources were also evaluated in vitro to measure acid-binding capacity (ABC) and Ca solubility at different pH values. Ca chloride showed the highest solubility of Ca, with TCP showing the highest ABC. Ross male broiler-chicks were sorted by BW at 1 d post-hatch and assigned to 5 cages per diet with 5 birds per cage. Twelve diets were arranged in a 3×4 factorial of the 3 Ca sources and 4 levels of NPP (0.3%, 0.35%, 0.4% or 0.45%) consisting of 4 added P levels (Ca(H2PO4)2) with a high dose of phytase (1,150 U/kg) in all diets. On d 14 post-hatch, 3 birds were euthanized, and ileal digesta and the right tibia were collected to determine ileal Ca and P digestibility and bone mineralization, respectively. Feed intake (FI) and weight gain (WG) on d 14 was higher (P<0.01) with TCP and limestone than with Ca chloride. Added P increased the tibia weight and tibia ash content in chicks fed TCP up to 0.4% NPP and limestone up to 0.35% NPP. Calcium ileal digestibility was higher (P<0.01) with Ca chloride (73.7%) than with limestone (67.1%) or TCP (66.8%), which increased (P<0.05) with added levels of P from monocalcium phosphate. Phosphorus ileal digestibility was not affected by the Ca source and increased (P<0.001) with added levels of NPP. It can be concluded that starting broilers responded better to low-soluble Ca sources compared to high-soluble sources. A level of 0.35%-0.40% NPP with a high dose of phytase (1,150 U/kg) in diets including limestone or TCP is sufficient to guarantee performance and bone formation for broiler chickens from d 0 to d 14. PMID:25638469

  10. The association between serum thyroid-stimulating hormone in its reference range and bone status in postmenopausal American women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Evidence suggests that hyperthyroidism adversely affects bone, but the condition is rare and probably contributes little to postmenopausal osteoporosis. Subclinical hyperthyroidism, which can result from treatment with L-thyroxine, is more common, but its relationship to osteoporosis and fracture is...

  11. Global skeletal uptake of 99mTc-methylene diphosphonate (GSU) in patients affected by endocrine diseases: comparison with biochemical markers of bone turnover.

    PubMed

    Scillitani, A; Dicembrino, F; Chiodini, I; Minisola, S; Fusilli, S; Di Giorgio, A; Garrubba, M; D'Aloiso, L; Frusciante, V; Torlontano, M; Modoni, S; Trischitta, V; Trischitta, V; Carnevale, V

    2002-10-01

    This study aimed to clinically validate the global skeletal uptake (GSU) of (99m)Tc-methylene diphosphonate ((99m)Tc-MDP), and to compare it with a marker of bone formation (i.e. serum osteocalcin or OC) and an index of bone resorption (i.e. urinary deoxypyridinoline or U-DPD) in different endocrine disorders affecting the skeleton. We studied 29 female patients with thyrotoxicosis (TT), 27 with primary hyperparathyroidism (PHPT), 16 with acromegaly (AC), 15 with Cushing's syndrome (CS), and altogether 110 healthy women matched for age, BMI and menstrual status. In all subjects total body digital scan images (TBDS) were acquired at 5 min and at 4 h after the administration of (99m)Tc-MDP; the whole body retention (WBR) of the tracer was measured by counting two identical sets of rectangular ROIs, and GSU was subsequently calculated by drawing an irregular ROI on 4 h TBDS images. Serum OC was assessed by IRMA and urinary DPD by fluorometric detection after reverse phase high pressure chromatography. In TT patients GSU (40.0 +/- 5.1 vs 36.5 +/- 4.8%), OC (19.1 +/- 11.8 vs 7.1 +/- 2.9 microg/l) and U-DPD (62.4 +/- 42.7 vs 19.5 +/- 5.3 pmol/pmol) were significantly ( p<0.01) higher than in controls. PHPT patients showed GSU (47.2 +/- 6.6 vs 37.8 +/- 5.3%), OC (38.6 +/- 40.9 vs 8.2 +/- 2.5 microg/l), and U-DPD (55.0 +/- 51.3 vs 21.9 +/- 6.1 pmol/pmol) values significantly ( p<0.001) higher than controls. In CS patients, GSU (39.6 +/- 6.4 vs 32.7 +/- 3.5%; p<0.01) and U-DPD (22.8 +/- 8.4 vs 16.5 +/- 2.7 pmol/pmol; p<0.05) were higher, whereas OC (3.6 +/- 2.4 vs 5.2 +/- 1.9 mg/l; p<0,05) was lower than in controls. In AC patients, GSU (34.9 +/- 5.3 vs 35.2 +/- 3.4%) did not differ significantly from controls, whereas OC (16.8 +/- 8.8 vs 6.9 +/- 2.9 microg/l; p<0.001) and U-DPD (30.9 +/- 13.6 vs 21.0 +/- 5.7 pmol/pmol; p<0.01) were higher. Stepwise multivariate linear regression analysis was performed with disease activity, creatinine clearance, age, and years since

  12. Managing adverse effects of glaucoma medications

    PubMed Central

    Inoue, Kenji

    2014-01-01

    Glaucoma is a chronic, progressive disease in which retinal ganglion cells disappear and subsequent, gradual reductions in the visual field ensues. Glaucoma eye drops have hypotensive effects and like all other medications are associated with adverse effects. Adverse reactions may either result from the main agent or from preservatives used in the drug vehicle. The preservative benzalkonium chloride, is one such compound that causes frequent adverse reactions such as superficial punctate keratitis, corneal erosion, conjunctival allergy, and conjunctival injection. Adverse reactions related to main hypotensive agents have been divided into those affecting the eye and those affecting the entire body. In particular, β-blockers frequently cause systematic adverse reactions, including bradycardia, decrease in blood pressure, irregular pulse and asthma attacks. Prostaglandin analogs have distinctive local adverse reactions, including eyelash bristling/lengthening, eyelid pigmentation, iris pigmentation, and upper eyelid deepening. No systemic adverse reactions have been linked to prostaglandin analog eye drop usage. These adverse reactions may be minimized when they are detected early and prevented by reducing the number of different eye drops used (via fixed combination eye drops), reducing the number of times eye drops are administered, using benzalkonium chloride-free eye drops, using lower concentration eye drops, and providing proper drop instillation training. Additionally, a one-time topical medication can be given to patients to allow observation of any adverse reactions, thereafter the preparation of a topical medication with the fewest known adverse reactions can be prescribed. This does require precise patient monitoring and inquiries about patient symptoms following medication use. PMID:24872675

  13. Paget’s disease of the bone

    MedlinePlus

    Tests that may indicate Paget's disease include: Bone scan Bone x-ray Elevated markers of bone breakdown (for instance, N-telopeptide) This disease may also affect the results of the following tests: ...

  14. Pregnancy, Breastfeeding, and Bone Health

    MedlinePlus

    ... supported by your browser. Home Osteoporosis Women Pregnancy, Breastfeeding, and Bone Health Publication available in: PDF (63 ... to get enough calcium during pregnancy and breastfeeding. Breastfeeding and Bone Health Breastfeeding also affects a mother’s ...

  15. Graphite-reinforced bone cement

    NASA Technical Reports Server (NTRS)

    Knoell, A. C.

    1976-01-01

    Chopped graphite fibers added to surgical bone cement form bonding agent with mechanical properties closely matched to those of bone. Curing reaction produces less heat, resulting in reduced traumatization of body tissues. Stiffness is increased without affecting flexural strength.

  16. Bone Marrow Aspiration and Biopsy

    MedlinePlus

    ... the bone marrow and capability for blood cell production, including red blood cells (RBCs), white blood cells ( ... can affect the bone marrow and blood cell production. A specialist who has expertise in the diagnosis ...

  17. Adverse reactions to sulfites

    PubMed Central

    Yang, William H.; Purchase, Emerson C.R.

    1985-01-01

    Sulfites are widely used as preservatives in the food and pharmaceutical industries. In the United States more than 250 cases of sulfite-related adverse reactions, including anaphylactic shock, asthmatic attacks, urticaria and angioedema, nausea, abdominal pain and diarrhea, seizures and death, have been reported, including 6 deaths allegedly associated with restaurant food containing sulfites. In Canada 10 sulfite-related adverse reactions have been documented, and 1 death suspected to be sulfite-related has occurred. The exact mechanism of sulfite-induced reactions is unknown. Practising physicians should be aware of the clinical manifestations of sulfite-related adverse reactions as well as which foods and pharmaceuticals contain sulfites. Cases should be reported to health officials and proper advice given to the victims to prevent further exposure to sulfites. The food industry, including beer and wine manufacturers, and the pharmaceutical industry should consider using alternative preservatives. In the interim, they should list any sulfites in their products. PMID:4052897

  18. Bone Diseases

    MedlinePlus

    ... also avoid smoking and drinking too much alcohol. Bone diseases can make bones easy to break. Different kinds ... Bones can also develop cancer and infections Other bone diseases, which are caused by poor nutrition, genetics, or ...

  19. Bone Grafts

    MedlinePlus

    ... repair and rebuild diseased bones in your hips, knees, spine, and sometimes other bones and joints. Grafts can also repair bone loss caused by some types of fractures or cancers. Once your body accepts the bone ...

  20. Scientists Trace Adversity's Toll

    ERIC Educational Resources Information Center

    Sparks, Sarah D.

    2012-01-01

    The stress of a spelling bee or a challenging science project can enhance a student's focus and promote learning. But the stress of a dysfunctional or unstable home life can poison a child's cognitive ability for a lifetime, according to new research. Those studies show that stress forms the link between childhood adversity and poor academic…

  1. Chronic low dose tumor necrosis factor-α (TNF) suppresses early bone accrual in young mice by inhibiting osteoblasts without affecting osteoclasts.

    PubMed

    Gilbert, L C; Chen, H; Lu, X; Nanes, M S

    2013-09-01

    The inflammatory cytokine tumor necrosis factor-α (TNF-α) is known to cause bone resorption and inhibit bone formation in arthritis and aging but less is known about TNF effects in the young growing skeleton. While investigating the mechanism of bone loss in TNF transgenic mice, we identified an early TNF-sensitive period marked by suppression of osteoblasts and bone accrual as the sole mechanism of TNF action, without an effect on osteoclasts or bone resorption. TgTNF mice express low concentrations of hTNFα (≤5 pg/ml). Osteoblasts cultured from TgTNF mice express reduced levels of RUNX2, Osx, alkaline phosphatase, bone sialoprotein, and osteocalcin and have delayed formation of mineralized nodules. Early accrual of bone in TgTNF mice is suppressed until 6 weeks of age, after which the rate of bone accrual normalizes without catch up. Histomorphometry revealed that TgTNF mice fail to generate a transient surge in osteoblast number that is seen in wild type (WT) mice at 4 weeks. Osteoclasts, TRAP staining, erosive surfaces, serum CTx, and OPG/RANKL expression did not differ between young TgTNF and WT mice. Canonical Wnts and signaling through β-catenin were reduced in TgTNF mice at 4 weeks and partially recovered by 12 weeks, associated with reduced cytoplasm to nuclear transfer of β-catenin and Wnt regulated genes. TgTNF mice were crossed with BatGal Wnt reporter mice. Active Wnt signaling in tibial trabecular lining cells was reduced in TgTNF mice at 4 weeks compared to control littermates. Our results demonstrate that a low dose inflammatory stimulus is sufficient to inhibit the early surge in osteoblasts and optimal bone formation of young mice independent of changes in osteoclasts. TNF inhibition of the Wnt pathway contributes to the suppression of osteoblasts. PMID:23756233

  2. [Determinants of bone quality and strength independent of bone remodeling].

    PubMed

    Saito, Mitsuru; Marumo, Keishi

    2016-01-01

    Bone mineral density(BMD)and bone microstructure are regulated mainly by bone remodeling. In contrast, bone collagen enzymatic immature and mature cross-links and advanced glycation end products such as pentosidine and carboxyl methyl lysine are affected by various factors. Aging bone tissue is repaired in the process of bone remodeling. However, deterioration of bone material properties markedly advances due to increases in oxidative stress, glycation stress, reactive oxygen species, carbonyl stress associated with aging and reduced sex hormone levels, and glucocorticoid use. To improve bone material properties in osteoporosis, we should use different drug (Saito M, Calcif Tissue Int, REVIEW, 97;242-261, 2015). In this review, we summarized determinants of bone quality and strength independent of bone remodeling. PMID:26728528

  3. Effects of a prolonged submersion on bone strength and metabolism in young healthy submariners.

    PubMed

    Luria, Tal; Matsliah, Yinnon; Adir, Yochai; Josephy, Noam; Moran, Daniel S; Evans, Rachel K; Abramovich, Amir; Eliakim, Alon; Nemet, Dan

    2010-01-01

    Submariners taking part in prolonged missions are exposed to environmental factors that may adversely affect bone health. Among these, relatively high levels of CO(2), lack of sunlight exposure affecting vitamin D metabolism, limited physical activity, and altered dietary habits. The aims of this study were to examine the effect of a prolonged submersion (30 days) on changes in bone strength using quantitative bone speed of sound and in markers of bone metabolism that include bone turnover (BAP, PINP, TRAP5b, and CTx) and endocrine regulators (serum calcium, PTH, and 25[OH]D) in a group of 32 young healthy male submariners. The prolonged submersion led to increases in body weight and BMI and to a decrease in fitness level. There was a significant decrease in bone strength following the submersion. Speed of sound exhibited continued decline at 4 weeks after return to shore and returned to baseline levels at the 6-month follow-up. There was a significant increase in circulating calcium level. PTH and 25(OH)D levels decreased significantly. Significant decreases were observed in both TRAP5b and CTx levels, markers of bone resorption, as well as in N-terminal propeptide of type I collagen (PINP), a bone formation marker. Prolonged submersion led to a significant decrease in bone strength, accompanied by an overall decrease in bone metabolism. Bone strength was regained only 6 months after return to shore. Prevention and/or rehabilitation programs should be developed following periods of relative disuse even for young submariners. The effects of repeated prolonged submersions on bone health are yet to be determined. PMID:19882096

  4. Benzo(a)pyrene and 7,12-dimethylbenz(a)anthrecene differentially affect bone marrow cells of the lymphoid and myeloid lineages

    SciTech Connect

    Galvan, Noe; Page, Todd J.; Czuprynski, Charles J.; Jefcoate, Colin R. . E-mail: jefcoate@facstaff.wisc.edu

    2006-06-01

    Polycyclic aromatic hydrocarbons (PAHs) are common environmental contaminants that are carcinogenic and immunosuppressive. Benzo(a)pyrene (BP) and 7,12-dimethylbenz(a)anthracene (DMBA) are two prototypic PAHs known to impair the cell-mediated and humoral immune responses. We have previously shown that, in C57BL/6J mice, total bone marrow (BM) cellularity decreased two-fold following intraperitoneal DMBA treatment but not BP treatment. Here, we have used flow cytometry to demonstrate that BP and DMBA differentially alter the lymphoid and myeloid lineages. Following DMBA treatment, the pro/pre B-lymphocytes (B220{sup lo}/IgM{sup -}) and the immature B-lymphocytes (B220{sup lo}/IgM{sup +}) significantly decreased, while the mature B-lymphocytes (B220{sup hi}/IgM{sup +}) remained unaffected. In contrast, BP treatment decreased the pro/pre B-lymphocytes, and did not affect the immature B-lymphocytes or mature B-lymphocytes. The Gr-1{sup +} cells of the myeloid lineage were depleted 50% following DMBA treatment and only minimally depleted following BP treatment. Interestingly, the monocytes (7/4{sup +}1A8{sup lo}) and neutrophils (7/4{sup +}1A8{sup hi}) within this Gr-1{sup +} population were differentially affected by these PAHs. Monocytes and neutrophils were depleted following DMBA treatment whereas neutrophils decreased and monocytes increased following BP treatment. Although TNF{alpha} and CYP1B1 are implicated as essential mediators of hypocellularity, the similar induction of TNF{alpha} mRNA and CYP1B1 mRNA in the BM by BP and DMBA suggests that they are not limiting factors in mediating the different effects of these PAHs. Given that similar amounts of BP and DMBA reach the BM when administered intraperitoneally, their differential effects on the lymphoid and myeloid lineages probably stem from differences in reactive metabolites such as PAH quinones and PAH-dihydrodiol-epoxides.

  5. Wnt Signaling in Bone

    PubMed Central

    Kubota, Takuo; Michigami, Toshimi; Ozono, Keiichi

    2010-01-01

    Wnt signaling is involved not only in embryonic development but also in maintenance of homeostasis in postnatal tissues. Multiple lines of evidence have increased understanding of the roles of Wnt signaling in bone since mutations in the LRP5 gene were identified in human bone diseases. Canonical Wnt signaling promotes mesenchymal progenitor cells to differentiate into osteoblasts. The canonical Wnt/β-catenin pathway possibly through Lrp6, a co-receptor for Wnts as well as Lrp5, in osteoblasts regulates bone resorption by increasing the OPG/RANKL ratio. However, endogenous inhibitors of Wnt signaling including sclerostin block bone formation. Regulation of sclerostin appears to be one of the mechanisms of PTH anabolic actions on bone. Since sclerostin is almost exclusively expressed in osteocytes, inhibition of sclerostin is the most promising design. Surprisingly, Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum, but not by directly promoting bone formation. Pharmacological intervention may be considered in many components of the canonical Wnt signaling pathway, although adverse effects and tumorigenicity to other tissues are important. More studies will be needed to fully understand how the Wnt signaling pathway actually influences bone metabolism and to assure the safety of new interventions. PMID:23926379

  6. Histone Deacetylases in Bone Development and Skeletal Disorders.

    PubMed

    Bradley, Elizabeth W; Carpio, Lomeli R; van Wijnen, Andre J; McGee-Lawrence, Meghan E; Westendorf, Jennifer J

    2015-10-01

    Histone deacetylases (Hdacs) are conserved enzymes that remove acetyl groups from lysine side chains in histones and other proteins. Eleven of the 18 Hdacs encoded by the human and mouse genomes depend on Zn(2+) for enzymatic activity, while the other 7, the sirtuins (Sirts), require NAD2(+). Collectively, Hdacs and Sirts regulate numerous cellular and mitochondrial processes including gene transcription, DNA repair, protein stability, cytoskeletal dynamics, and signaling pathways to affect both development and aging. Of clinical relevance, Hdacs inhibitors are United States Food and Drug Administration-approved cancer therapeutics and are candidate therapies for other common diseases including arthritis, diabetes, epilepsy, heart disease, HIV infection, neurodegeneration, and numerous aging-related disorders. Hdacs and Sirts influence skeletal development, maintenance of mineral density and bone strength by affecting intramembranous and endochondral ossification, as well as bone resorption. With few exceptions, inhibition of Hdac or Sirt activity though either loss-of-function mutations or prolonged chemical inhibition has negative and/or toxic effects on skeletal development and bone mineral density. Specifically, Hdac/Sirt suppression causes abnormalities in physiological development such as craniofacial dimorphisms, short stature, and bone fragility that are associated with several human syndromes or diseases. In contrast, activation of Sirts may protect the skeleton from aging and immobilization-related bone loss. This knowledge may prolong healthspan and prevent adverse events caused by epigenetic therapies that are entering the clinical realm at an unprecedented rate. In this review, we summarize the general properties of Hdacs/Sirts and the research that has revealed their essential functions in bone forming cells (e.g., osteoblasts and chondrocytes) and bone resorbing osteoclasts. Finally, we offer predictions on future research in this area and the

  7. Radiation-blocking shields to localize periarticular radiation precisely for prevention of heterotopic bone formation around uncemented total hip arthroplasties

    SciTech Connect

    Jasty, M.; Schutzer, S.; Tepper, J.; Willett, C.; Stracher, M.A.; Harris, W.H. )

    1990-08-01

    Sixteen patients (18 hips) were treated with localized radiation therapy limited to periarticular regions surrounding the femoral neck by shielding the prosthesis and the adjacent regions to prevent heterotopic bone formation around the uncemented prosthesis. All hips received 1500 rads. Eight of these hips were irradiated after excising severe heterotopic bone, five because they developed extensive heterotopic ossification in the opposite hip, and five others because they were considered to be at high risk for developing heterotopic ossification. Only two of the 18 hips developed a small amount of heterotopic bone after localized periarticular radiation. All wounds healed primarily. No progressive radiolucencies developed at the bone-prosthesis interface. There was only one trochanteric nonunion of six trochanteric osteotomies. Localized periarticular radiation therapy with precision shielding of the prosthetic components and adjacent skeletal structures is an effective means to prevent heterotopic bone formation around cementless total hip arthroplasties. It also has the advantage of not adversely affecting the healing of the trochanteric osteotomy.

  8. Bone Mineral Density Determinations by Dual-Energy x-ray Absorptiometry in the Management of Patients with Marfan Syndrome—Some Factors Which Affect the Measurement

    PubMed Central

    Peterson, Margaret G.E.; Schneider, Robert; Davis, Jessica G.; Burke, Stephen W.; Boachie-Adjei, Oheneba; Mueller, Charles M.; Raggio, Cathleen L.

    2006-01-01

    Reduced bone mineral density (BMD) was sporadically reported in patients with Marfan syndrome. This may or may not place the Marfan patient at increased risk for bone fracture. In comparing the BMDs of our patients with those reported in the literature, it seemed that agreement between values, and hence the degree of osteoporosis or osteopenia reported, was dependent on the instrumentation used. The objective of this study was to statistically assess this impression. Bone mineral density measurements from our previously published study of 30 adults with Marfan syndrome performed on a Lunar DPXL machine were compared with studies published between 1993–2000 measured using either Lunar or Hologic bone densitometry instruments. The differences of our measurements compared with those made on other Lunar machines were not statistically significant, but did differ significantly with published results from Hologic machines (P < 0.001). Before progress can be made in the assessment of BMD and fracture risk in Marfan patients and in the evidence-based orthopedic management of these patients, standardization of instrumental bone density determinations will be required along with considerations of height, obesity, age, and sex. PMID:18751776

  9. [Inflammatory bowel disease and bone decreased bone mineral density].

    PubMed

    Hisamatsu, Tadakazu; Wada, Yasuyo; Kanai, Takanori

    2015-11-01

    Metabolic bone diseases such as osteopenia and osteoporosis increase the risk of bone fracture that negatively affects quality of life of individuals. Patients with inflammatory bowel disease(IBD), including ulcerative colitis(UC)and Crohn's disease(CD), have been shown to be at increased risk of decreased bone mineral density, however frequency of metabolic bone disease in IBD and identified risk factors are varied among reports. PMID:26503868

  10. Biomaterials and bone mechanotransduction

    NASA Technical Reports Server (NTRS)

    Sikavitsas, V. I.; Temenoff, J. S.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

    2001-01-01

    Bone is an extremely complex tissue that provides many essential functions in the body. Bone tissue engineering holds great promise in providing strategies that will result in complete regeneration of bone and restoration of its function. Currently, such strategies include the transplantation of highly porous scaffolds seeded with cells. Prior to transplantation the seeded cells are cultured in vitro in order for the cells to proliferate, differentiate and generate extracellular matrix. Factors that can affect cellular function include the cell-biomaterial interaction, as well as the biochemical and the mechanical environment. To optimize culture conditions, good understanding of these parameters is necessary. The new developments in bone biology, bone cell mechanotransduction, and cell-surface interactions are reviewed here to demonstrate that bone mechanotransduction is strongly influenced by the biomaterial properties.

  11. [Adverse reaction of pseudoephedrine].

    PubMed

    López Lois, G; Gómez Carrasco, J A; García de Frías, E

    2005-04-01

    We present a case of a 7 years old girl who developed an episode of myoclonic movements and tremors after being medicated with a not well quantified amount of a pseudoephedrine/antihistamine combination. We want to highlight the potential toxicity of pseudoephedrine, usually administered as part of cold-syrup preparations which are used for symptomatic treatment of upper respiratory tract cough and congestion associated with the common cold and allergic rhinitis. Although these products are generally considered to be safe either by physicians and parents, we can't underestimate the potential adverse events and toxic effects that can occur when administering these medications. PMID:15826569

  12. Living Bones, Strong Bones

    NASA Video Gallery

    In this classroom activity, engineering, nutrition, and physical activity collide when students design and build a healthy bone model of a space explorer which is strong enough to withstand increas...

  13. Experiment K-314: Fetal and neonatal rat bone and joint development following in Utero spaceflight

    NASA Technical Reports Server (NTRS)

    Sabelman, E. E.; Holton, E. M.; Arnaud, C. D.

    1981-01-01

    Infant rat limb specimens from Soviet and U.S. ground-based studies were examined by radiography, macrophotography, histologic sectioning and staining and scanning electron microscopy. A comparison was conducted between vivarium and flight-type diets suggesting that nutritional obesity may adversely affect pregnancy. Data were obtained on maturation of ossification centers, orientation of collagen fibers in bone, tendon and ligaments, joint surface texture and spatial relationships of bones of the hind limb. Computer reconstructions of the knee and hip show promise as a means of investigating the etiology of congenital hip dislocation.

  14. Bone scan

    MedlinePlus

    ... scan is an imaging test used to diagnose bone diseases and find out how severe they are. How ... a 3-phase bone scan. To evaluate metastatic bone disease, images are taken only after the 3- to ...

  15. Bone Cancer

    MedlinePlus

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  16. Bone scan

    MedlinePlus

    A bone scan is an imaging test used to diagnose bone diseases and find out how severe they are. ... A bone scan involves injecting a very small amount of radioactive material (radiotracer) into a vein. The substance travels through ...

  17. Bone Density

    MedlinePlus

    ... bone health. It compares your bone density, or mass, to that of a healthy person who is ... Whether your osteoporosis treatment is working Low bone mass that is not low enough to be osteoporosis ...

  18. Bone Cancer

    MedlinePlus

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another part of the body is more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 ...

  19. Screening for adverse events.

    PubMed

    Karson, A S; Bates, D W

    1999-02-01

    Adverse events (AEs) in medical patients are common, costly, and often preventable. Development of quality improvement programs to decrease the number and impact of AEs demands effective methods for screening for AEs on a routine basis. Here we describe the impact, types, and potential causes of AEs and review various techniques for identifying AEs. We evaluate the use of generic screening criteria in detail and describe a recent study of the sensitivity and specificity of individual generic screening criteria and combinations of these criteria. In general, the most sensitive screens were the least specific and no small sub-set of screens identified a large percentage of adverse events. Combinations of screens that were limited to administrative data were the least expensive, but none were particularly sensitive, although in practice they might be effective since routine screening is currently rarely done. As computer systems increase in sophistication sensitivity will improve. We also discuss recent studies that suggest that programs that screen for and identify AEs can be useful in reducing AE rates. While tools for identifying AEs have strengths and weaknesses, they can play an important role in organizations' quality improvement portfolios. PMID:10468381

  20. Adverse Drug Reactions of the Lower Extremities.

    PubMed

    Adigun, Chris G

    2016-07-01

    Adverse drug reactions (ADRs) are a common cause of dermatologic consultation, involving 2 to 3 per 100 medical inpatients in the United States. Female patients are 1.3 to 1.5 times more likely to develop ADRs, except in children less than 3 years of age, among whom boys are more often affected. Certain drugs are more frequent causes, including aminopenicillins, trimethoprim-sulfamethoxazole, and nonsteroidal antiinflammatory drugs. Chemotherapeutic agents commonly cause adverse reactions to the skin and nails, with certain agents causing particular patterns of reactions. ADRs can involve any area of the skin; the appendages, including hair and nails; as well as mucosa. PMID:27215159

  1. Vitamin B-12 supplementation of rural Mexican women changes biochemical B-12 status indicators but does not affect hematology or a bone turnover marker

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Based on the high prevalence of low serum vitamin B-12 concentrations and low dietary intake of the vitamin in Latin American studies including research in Mexico, it appears that vitamin B-12 deficiency is common. Whether this is associated with adverse effects on human function is unknown. To eval...

  2. Is breastfeeding related to bone properties? A longitudinal analysis of associations between breastfeeding duration and pQCT parameters in children and adolescents.

    PubMed

    Kühn, Tilman; Kroke, Anja; Remer, Thomas; Schönau, Eckhard; Buyken, Anette E

    2014-10-01

    Nutritive and bioactive components of human milk could be involved in programming metabolic systems that affect bone growth throughout the life course. Bone properties in childhood and adolescence might differ, depending on breastfeeding duration. Thus, breastfeeding could be a relevant factor in the context of primary osteoporosis prevention. The prospective association between breastfeeding duration and bone properties was investigated using the data of 284 participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study. Breastfeeding duration was assessed during infancy. Bone properties were measured by peripheral quantitative computed tomography (pQCT) at ages 5-23 years. Cortical volumetric bone mineral density, cortical bone mineral content, strength strain index, total cross-sectional area of the bone and cross-sectional area of the cortical bone were determined at the 65% site of the radius. Linear regression analyses were performed to check for differences in pQCT parameters of subjects who had not or shortly been breastfed (0-16 weeks) and subjects who had been breastfed for a long duration (≥17 weeks). Multivariable models adjusted for age, gender, forearm length, muscle cross-sectional area, body mass index standard deviation score (SDS), height SDS and socio-economic status did not yield associations between breastfeeding duration and pQCT parameters. These findings suggest neither protective nor adverse effects of prolonged breastfeeding on bone health in childhood and adolescence. Influences of early nutrition on bone growth might be overridden by current effects of mechanical loads on bone physiology. PMID:22909290

  3. Sire carcass breeding values affect body composition in lambs--2. Effects on fat and bone weight and their distribution within the carcass as measured by computed tomography.

    PubMed

    Anderson, F; Williams, A; Pannier, L; Pethick, D W; Gardner, G E

    2016-06-01

    This study assessed the effect of paternal Australian Sheep Breeding Values for post weaning c-site eye muscle depth (PEMD) and fat depth (PFAT), and post weaning weight (PWWT) on the composition of lamb carcasses. Composition was measured using computed tomography scans of 1665 lambs which were progeny of 85 Maternal, 115 Merino and 155 Terminal sires. Reducing sire PFAT decreased carcass fat weight by 4.8% and increased carcass bone by 1.3% per unit of PFAT (range 5.1 mm). Increasing sire PEMD reduced carcass fat weight by 3.8% in Maternal and 2% in Terminal sired lambs per unit of PEMD (range 4.3 and 7.8 mm), with no impact on bone. Increasing sire PWWT reduced carcass fat weight, but only at some experimental locations. Differences in composition varied between sire types with Maternal sired lambs having the most fat and Merino sired lambs the greatest bone weight. Genetic effects on fatness were greater than the environmental or production factor effects, with the converse true of bone. PMID:26914513

  4. ISMP Adverse Drug Reactions

    PubMed Central

    2013-01-01

    The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA’s) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner. PMID:24421544

  5. [Cutaneous adverse drug reactions].

    PubMed

    Lebrun-Vignes, B; Valeyrie-Allanore, L

    2015-04-01

    Cutaneous adverse drug reactions (CADR) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Exanthematous eruptions, urticaria and vasculitis are the most common forms of CADR. Fixed eruption is uncommon in western countries. Serious reactions (fatal outcome, sequelae) represent 2% of CADR: bullous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), DRESS (drug reaction with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome) and acute generalized exanthematous pustulosis (AGEP). These forms must be quickly diagnosed to guide their management. The main risk factors are immunosuppression, autoimmunity and some HLA alleles in bullous reactions and DRESS. Most systemic drugs may induce cutaneous adverse reactions, especially antibiotics, anticonvulsivants, antineoplastic drugs, non-steroidal anti-inflammatory drugs, allopurinol and contrast media. Pathogenesis includes immediate or delayed immunologic mechanism, usually not related to dose, and pharmacologic/toxic mechanism, commonly dose-dependent or time-dependent. In case of immunologic mechanism, allergologic exploration is possible to clarify drug causality, with a variable sensitivity according to the drug and to the CADR type. It includes epicutaneous patch testing, prick test and intradermal test. However, no in vivo or in vitro test can confirm the drug causality. To determine the cause of the eruption, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis is required, completed with a literature search. A reporting to pharmacovigilance network is essential in case of a serious CADR whatever the suspected drug and in any case if the involved drug is a newly marketed one or unusually related to cutaneous reactions. PMID:25458866

  6. What Happens After Treatment for Bone Cancer?

    MedlinePlus

    ... cancer? Can I get another cancer after having bone cancer? Lifestyle changes after treatment for bone cancer How does having bone cancer affect your ... talk to your cancer care team about any changes or problems you notice and any ... extensive bone surgery, a program of rehabilitation and physical therapy ...

  7. Odanacatib treatment affects trabecular and cortical bone in the femur of postmenopausal women: results of a two-year placebo-controlled trial.

    PubMed

    Engelke, Klaus; Fuerst, Thomas; Dardzinski, Bernard; Kornak, John; Ather, Shabana; Genant, Harry K; de Papp, Anne

    2015-01-01

    Odanacatib, a selective cathepsin K inhibitor, increases areal bone mineral density (aBMD) at the spine and hip of postmenopausal women. To gain additional insight into the effects on trabecular and cortical bone, we analyzed quantitative computed tomography (QCT) data of postmenopausal women treated with odanacatib using Medical Image Analysis Framework (MIAF; Institute of Medical Physics, University of Erlangen, Erlangen, Germany). This international, randomized, double-blind, placebo-controlled, 2-year, phase 3 trial enrolled 214 postmenopausal women (mean age 64 years) with low aBMD. Subjects were randomized to odanacatib 50 mg weekly (ODN) or placebo (PBO); all participants received calcium and vitamin D. Hip QCT scans at 24 months were available for 158 women (ODN: n = 78 women; PBO: n = 80 women). There were consistent and significant differential treatment effects (ODN-PBO) for total hip integral (5.4%), trabecular volumetric BMD (vBMD) (12.2%), and cortical vBMD (2.5%) at 24 months. There was no significant differential treatment effect on integral bone volume. Results for bone mineral content (BMC) closely matched those for vBMD for integral and trabecular compartments. However, with small but mostly significant differential increases in cortical volume (1.0% to 1.3%) and thickness (1.4% to 1.9%), the percentage cortical BMC increases were numerically larger than those of vBMD. With a total hip BMC differential treatment effect (ODN-PBO) of nearly 1000 mg, the proportions of BMC attributed to cortical gain were 45%, 44%, 52%, and 40% for the total, neck, trochanter, and intertrochanter subregions, respectively. In postmenopausal women treated for 2 years, odanacatib improved integral, trabecular, and cortical vBMD and BMC at all femur regions relative to placebo when assessed by MIAF. Cortical volume and thickness increased significantly in all regions except the femoral neck. The increase in cortical volume and BMC paralleled the increase in

  8. Fractures and Biomechanical Characteristics of the Bone

    PubMed Central

    Velnar, Tomaz; Bunc, Gorazd; Gradisnik, Lidija

    2016-01-01

    The biological tissue is affected by external and internal deformation forces: tractive/tensile forces, shearing and compressive forces. The bone is deformed under the effect of a force. If the load exceeds the bone solidity limitation, fracture occurs. A mature bone consists of compact and spongy bone tissue. The basic structural unit of the cortical bone tissue are osteons and spongiosa consists of a network of bone trabeculae. The organic and mineral parts of the bone are responsible for the special bone characteristics. The effect of a physical activity on the mechanical characteristics of the bone is associated with the intensity of the load. Fractures are more common in elderly people as the bone structure is altered on account of osteoporosis and contains less bone tissue. Biomechanical characteristics with anatomic and histological bone structure as well as osteoporotic hip fractures are described in the paper. PMID:27110433

  9. Freezing of Rat Tibiae at -20°C Does Not Affect the Mechanical Properties of Intramedullary Bone/Implant-Interface: Brief Report

    PubMed Central

    Diefenbeck, Michael; Mückley, Thomas; Zankovych, Sergiy; Bossert, Jörg; Jandt, Klaus D; Schrader, Christian; Schmidt, Jürgen; Finger, Ulrich; Faucon, Mathilde

    2011-01-01

    Background: The effects of freezing-thawing cycles on intramedullary bone-implant interfaces have been studied in a rat model in mechanical pull-out tests. Implants: Twenty TiAl6V4 rods (Ø 0.8 mm, length 10 mm) implanted in rat tibiae Methods: 10 rats underwent bilateral tibial implantation of titanium rods. At eight weeks, the animals were sacrificed and tibiae harvested for biomechanical testing. Eight tibiae were frozen and stored at -20°C for 14 days, the remaining eight were evaluated immediately post-harvest. Pull-out tests were used to determine maximum force and interfacial shear strength. Results: There were no significant differences between fresh and those of the frozen-thawed group in maximum force or in interfacial shear strength. Conclusion: Frozen Storage of rat tibiae containing implants at -20° C has no effects on the biomechanical properties of Bone/ Implant interface. PMID:21760868

  10. Adverse childhood experiences and health anxiety in adulthood.

    PubMed

    Reiser, Sarah J; McMillan, Katherine A; Wright, Kristi D; Asmundson, Gordon J G

    2014-03-01

    Childhood experiences are thought to predispose a person to the development of health anxiety later in life. However, there is a lack of research investigating the influence of specific adverse experiences (e.g., childhood abuse, household dysfunction) on this condition. The current study examined the cumulative influence of multiple types of childhood adversities on health anxiety in adulthood. Adults 18-59 years of age (N=264) completed a battery of measures to assess adverse childhood experiences, health anxiety, and associated constructs (i.e., negative affect and trait anxiety). Significant associations were observed between adverse childhood experiences, health anxiety, and associated constructs. Hierarchical multiple regression analysis indicted that adverse childhood experiences were predictive of health anxiety in adulthood; however, the unique contribution of these experience were no longer significant following the inclusion of the other variables of interest. Subsequently, mediation analyses indicated that both negative affect and trait anxiety independently mediated the relationship between adverse childhood experiences and health anxiety in adulthood. Increased exposure to adverse childhood experiences is associated with higher levels of health anxiety in adulthood; this relationship is mediated through negative affect and trait anxiety. Findings support the long-term negative impact of cumulative adverse childhood experiences and emphasize the importance of addressing negative affect and trait anxiety in efforts to prevent and treat health anxiety. PMID:24011493

  11. Porous Surface Modified Bioactive Bone Cement for Enhanced Bone Bonding

    PubMed Central

    Huang, Li; Dong, Jingjing; Guo, Dagang; Mao, Mengmeng; Kong, Liang; Li, Yang; Wu, Zixiang; Lei, Wei

    2012-01-01

    Background Polymethylmethacrylate bone cement cannot provide an adhesive chemical bonding to form a stable cement-bone interface. Bioactive bone cements show bone bonding ability, but their clinical application is limited because bone resorption is observed after implantation. Porous polymethylmethacrylate can be achieved with the addition of carboxymethylcellulose, alginate and gelatin microparticles to promote bone ingrowth, but the mechanical properties are too low to be used in orthopedic applications. Bone ingrowth into cement could decrease the possibility of bone resorption and promote the formation of a stable interface. However, scarce literature is reported on bioactive bone cements that allow bone ingrowth. In this paper, we reported a porous surface modified bioactive bone cement with desired mechanical properties, which could allow for bone ingrowth. Materials and Methods The porous surface modified bioactive bone cement was evaluated to determine its handling characteristics, mechanical properties and behavior in a simulated body fluid. The in vitro cellular responses of the samples were also investigated in terms of cell attachment, proliferation, and osteoblastic differentiation. Furthermore, bone ingrowth was examined in a rabbit femoral condyle defect model by using micro-CT imaging and histological analysis. The strength of the implant–bone interface was also investigated by push-out tests. Results The modified bone cement with a low content of bioactive fillers resulted in proper handling characteristics and adequate mechanical properties, but slightly affected its bioactivity. Moreover, the degree of attachment, proliferation and osteogenic differentiation of preosteoblast cells was also increased. The results of the push-out test revealed that higher interfacial bonding strength was achieved with the modified bone cement because of the formation of the apatite layer and the osseointegration after implantation in the bony defect. Conclusions

  12. Deficiency of Thrombospondin-4 in Mice Does Not Affect Skeletal Growth or Bone Mass Acquisition, but Causes a Transient Reduction of Articular Cartilage Thickness

    PubMed Central

    Simon, Maciej; Peters, Stephanie; Baum, Wolfgang; Schett, Georg; Ruether, Wolfgang; Niemeier, Andreas; Schinke, Thorsten; Amling, Michael

    2015-01-01

    Although articular cartilage degeneration represents a major public health problem, the underlying molecular mechanisms are still poorly characterized. We have previously utilized genome-wide expression analysis to identify specific markers of porcine articular cartilage, one of them being Thrombospondin-4 (Thbs4). In the present study we analyzed Thbs4 expression in mice, thereby confirming its predominant expression in articular cartilage, but also identifying expression in other tissues, including bone. To study the role of Thbs4 in skeletal development and integrity we took advantage of a Thbs4-deficient mouse model that was analyzed by undecalcified bone histology. We found that Thbs4-deficient mice do not display phenotypic differences towards wildtype littermates in terms of skeletal growth or bone mass acquisition. Since Thbs4 has previously been found over-expressed in bones of Phex-deficient Hyp mice, we additionally generated Thbs4-deficient Hyp mice, but failed to detect phenotypic differences towards Hyp littermates. With respect to articular cartilage we found that Thbs4-deficient mice display transient thinning of articular cartilage, suggesting a protective role of Thbs4 for joint integrity. Gene expression analysis using porcine primary cells revealed that Thbs4 is not expressed by synovial fibroblasts and that it represents the only member of the Thbs gene family with specific expression in articular, but not in growth plate chondrocytes. In an attempt to identify specific molecular effects of Thbs4 we treated porcine articular chondrocytes with human THBS4 in the absence or presence of conditioned medium from porcine synovial fibroblasts. Here we did not observe a significant influence of THBS4 on proliferation, metabolic activity, apoptosis or gene expression, suggesting that it does not act as a signaling molecule. Taken together, our data demonstrate that Thbs4 is highly expressed in articular chondrocytes, where its presence in the

  13. Short bones

    MedlinePlus

    Short bones in the human body are often cube-like, their length, width, and height are all about the same. Short bones include the carpal bones of the hands and wrist, and the tarsal bones of the feet and ankles.

  14. Strontium increases vertebral bone volume in rats at a low dose that does not induce detectable mineralization defect.

    PubMed

    Grynpas, M D; Hamilton, E; Cheung, R; Tsouderos, Y; Deloffre, P; Hott, M; Marie, P J

    1996-03-01

    Low doses of strontium and fluoride were shown to increase bone formation and trabecular bone density in rodents. To assess whether strontium or fluoride affect the quality of the mineral at doses known to increase bone density, we have determined the effects of low doses of strontium and fluoride on bone formation and bone mineral characteristics in rats. Adult rats were given strontium alone (0.20%), fluoride alone (1 mg/kg per day), or the combined treatment for 8 weeks. Strontium levels in serum and femur were similar in groups treated with strontium alone or in combination, being about 5% of calcium levels. Biochemical and neutron activation analyses in femur showed that calcium and magnesium contents did not differ in the four group of rats, suggesting that strontium was incorporated in the apatite lattice of the bone minerals in the strontium-treated rats. The mineralized bone volume was significantly increased by 17% in the strontium-treated group, by 20% in the fluoride-treated group, and by 19% in rats given with the combined treatment. This was associated with increased osteoid surface, osteoblast surface, and double tetracycline labeled surfaces in the strontium-treated and fluoride-treated groups, showing that the number of bone forming sites was increased. However, the mineral apposition rate, the osteoid thickness, and the mineralization lag time were similar in controls and treated groups, reflecting the lack of deleterious effects of low doses of strontium and fluoride on bone mineralization. The density fractionation analysis measured in the femur also showed that neither strontium, nor fluoride at the low doses used, significantly altered the mineralization profile. The results indicate that treatment with low doses of strontium or fluoride increase the number of bone forming sites and vertebral bone volume in rats, but does not have detectable adverse effects on the mineral profile, bone mineral chemistry or bone matrix mineralization. PMID

  15. Bone scanning.

    PubMed

    Greenfield, L D; Bennett, L R

    1975-03-01

    Scanning is based on the uptake of a nuclide by the crystal lattice of bone and is related to bone blood flow. Cancer cells do not take up the tracer. Normally, the scan visualizes the highly vascular bones. Scans are useful and are indicated in metastatic bone disease, primary bone tumors, hematologic malignancies and some non-neoplastic diseases. The scan is more sensitive than x-ray in the detection of malignant diseases of the skeleton. PMID:1054210

  16. ADVERSE CUTANEOUS DRUG REACTION

    PubMed Central

    Nayak, Surajit; Acharjya, Basanti

    2008-01-01

    In everyday clinical practice, almost all physicians come across many instances of suspected adverse cutaneous drug reactions (ACDR) in different forms. Although such cutaneous reactions are common, comprehensive information regarding their incidence, severity and ultimate health effects are often not available as many cases go unreported. It is also a fact that in the present world, almost everyday a new drug enters market; therefore, a chance of a new drug reaction manifesting somewhere in some form in any corner of world is unknown or unreported. Although many a times, presentation is too trivial and benign, the early identification of the condition and identifying the culprit drug and omit it at earliest holds the keystone in management and prevention of a more severe drug rash. Therefore, not only the dermatologists, but all practicing physicians should be familiar with these conditions to diagnose them early and to be prepared to handle them adequately. However, we all know it is most challenging and practically difficult when patient is on multiple medicines because of myriad clinical symptoms, poorly understood multiple mechanisms of drug-host interaction, relative paucity of laboratory testing that is available for any definitive and confirmatory drug-specific testing. Therefore, in practice, the diagnosis of ACDR is purely based on clinical judgment. In this discussion, we will be primarily focusing on pathomechanism and approach to reach a diagnosis, which is the vital pillar to manage any case of ACDR. PMID:19967009

  17. Radioiodine Treatment and Thyroid Hormone Suppression Therapy for Differentiated Thyroid Carcinoma: Adverse Effects Support the Trend toward Less Aggressive Treatment for Low-Risk Patients

    PubMed Central

    Klein Hesselink, E.N.; Links, T.P.

    2015-01-01

    Over the past decades, the incidence of differentiated thyroid carcinoma (DTC) has steadily increased, with especially a growing number of low-risk patients. Whereas DTC used to be treated rather aggressively, it is now acknowledged that aggressive treatment does not affect outcome for low-risk patients and that it can induce adverse effects. In this review an overview of the most clinically relevant adverse effects of radioiodine treatment and thyroid hormone suppression therapy (THST) is presented, and the trend toward less aggressive treatment for low-risk patients is outlined. Salivary gland dysfunction occurs in roughly 30% of patients, and is probably due to the concentration of radioiodine in the salivary glands by the sodium/iodide symporter. Beta radiation from radioiodine can result in sialoadenitis and eventually fibrosis and loss of salivary function. Furthermore, patients can experience bone marrow dysfunction following radioiodine treatment. Although this is in general subclinical and transient, patients that receive very high cumulative radioiodine doses may be at risk for more severe bone marrow dysfunction. THST can induce adverse cardiovascular effects in patients with DTC, such as diastolic and systolic dysfunction, and also adverse vascular and prothrombotic effects have been described. Finally, the effects of THST on bone formation and resorption are outlined; especially postmenopausal women with DTC on THST seem to be at risk of bone loss. In the past years, advances have been made in preventing low-risk patients from being overtreated. Improved biomarkers are still needed to further optimize risk stratification and personalize medicine. PMID:26279993

  18. The effect of 5alpha-reductase inhibition with finasteride and dutasteride on bone mineral density in older men with benign prostatic hyperplasia.

    PubMed

    Mačukat, Indira Radin; Spanjol, Josip; Orlič, Zeljka Crncevič; Butorac, Marta Zuvič; Marinovič, Marin; Ćupič, Dora Fučkar

    2014-09-01

    Testosterone is converted to dihyrotestosterone by two isoenzymes of 5alpha-reductase. Finasteride and dutasteride are 5alpha-reductase inhibitors commonly used in the treatment of benign prostatic hyperplasia. We compared indices of bone mineral density in 50 men treated with finasteride, 50 men treated with dutasteride and 50 men as control. Bone mineral density of spine and hip were measured using dual energy X-ray absorptiometry. Bone formation was assessed by measuring serum osteocalcin and bone resorptionby measuring serum C-terminal telopeptide of collagen type 1. In addition serum total testosteron and estradiol were determined. The dutasteride group had significantly higher mean bone min- eral density, mean bone mineral content, mean T score, mean Z score at femoral neck and mean total hip Z score than control. Mean total testosterone and estradiol levels were higher in the dutasteride group. There were no significant dif- ferences between the groups in lumbar spine bone density parameters or bone turnover markers. Our results provide evidence that long-term 5alpha-reductase suppression does not adversely affect bone mineral density. Dutasteride therapy could have beneficial effect on bone density. PMID:25507347

  19. The effect of 5alpha-reductase inhibition with finasteride and dutasteride on bone mineral density in older men with benign prostatic hyperplasia.

    PubMed

    Mačukat, Indira Radin; Spanjol, Josip; Orlič, Zeljka Crncevič; Butorac, Marta Zuvič; Marinovič, Marin; Ćupič, Dora Fučkar

    2014-09-01

    Testosterone is converted to dihyrotestosterone by two isoenzymes of 5alpha-reductase. Finasteride and dutasteride are 5alpha-reductase inhibitors commonly used in the treatment of benign prostatic hyperplasia. We compared indices of bone mineral density in 50 men treated with finasteride, 50 men treated with dutasteride and 50 men as control. Bone mineral density of spine and hip were measured using dual energy X-ray absorptiometry. Bone formation was assessed by measuring serum osteocalcin and bone resorptionby measuring serum C-terminal telopeptide of collagen type 1. In addition serum total testosteron and estradiol were determined. The dutasteride group had significantly higher mean bone min- eral density, mean bone mineral content, mean T score, mean Z score at femoral neck and mean total hip Z score than control. Mean total testosterone and estradiol levels were higher in the dutasteride group. There were no significant dif- ferences between the groups in lumbar spine bone density parameters or bone turnover markers. Our results provide evidence that long-term 5alpha-reductase suppression does not adversely affect bone mineral density. Dutasteride therapy could have beneficial effect on bone density. PMID:25420363

  20. The adverse health effects of chronic cannabis use.

    PubMed

    Hall, Wayne; Degenhardt, Louisa

    2014-01-01

    This paper summarizes the most probable of the adverse health effects of regular cannabis use sustained over years, as indicated by epidemiological studies that have established an association between cannabis use and adverse outcomes; ruled out reverse causation; and controlled for plausible alternative explanations. We have also focused on adverse outcomes for which there is good evidence of biological plausibility. The focus is on those adverse health effects of greatest potential public health significance--those that are most likely to occur and to affect a substantial proportion of regular cannabis users. These most probable adverse effects of regular use include a dependence syndrome, impaired respiratory function, cardiovascular disease, adverse effects on adolescent psychosocial development and mental health, and residual cognitive impairment. PMID:23836598

  1. Low Bone Density

    MedlinePlus

    ... Density Exam/Testing › Low Bone Density Low Bone Density Low bone density is when your bone density ... people with normal bone density. Detecting Low Bone Density A bone density test will determine whether you ...

  2. Magnetic Resonance Evaluation of Multiple Myeloma at 3.0 Tesla: How Do Bone Marrow Plasma Cell Percentage and Selection of Protocols Affect Lesion Conspicuity?

    PubMed Central

    Takasu, Miyuki; Tamura, Takayuki; Kaichi, Yoko; Tanitame, Keizo; Akiyama, Yuji; Date, Shuji; Sakai, Akira; Kuroda, Yoshiaki; Awai, Kazuo

    2014-01-01

    Purpose To compare various pulse sequences in terms of percent contrast and contrast-to-noise ratio (CNR) for detection of focal multiple myeloma lesions and to assess the dependence of lesion conspicuity on the bone marrow plasma cell percent (BMPC%). Materials and Methods Sagittal T1-weighted FSE, fat-suppressed T2-weighted FSE (FS- T2 FSE), fast STIR and iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) imaging of the lumbar spine were performed (n = 45). Bone marrow (BM)-focal myeloma lesion percent contrast and CNR were calculated. Spearman rank correlation coefficients were obtained between percent contrast, CNR and BMPC%. Percent contrasts and CNRs were compared among the three imaging sequences. Results BM-focal lesion percent contrasts, CNRs and BMPC% showed significant negative correlations in the three fat-suppression techniques. Percent contrast and CNRs were significantly higher for FS- T2 FSE than for STIR (P<0.01, P<0.05, respectively), but no significant differences were found among the three fat-suppression methods in the low tumor load BM group. Conclusion The higher BMPC% was within BM, the less conspicuous the focal lesion was on fat-suppressed MRI. The most effective protocol for detecting focal lesions was FS- T2 FSE. In the high tumor load BM group, no significant differences in lesion conspicuity were identified among the three fat-suppression techniques. PMID:24489680

  3. Unreamed or RIA reamed nailing: an experimental sheep study using comparative histological assessment of affected bone tissue in an acute fracture model.

    PubMed

    Klein, Christian; Sprecher, Christoph; Rahn, Berton A; Green, James; Müller, Christof A

    2010-11-01

    The purpose of the present study was to evaluate the Reamer/Irrigator/Aspirator (RIA), a reaming system designed to incorporate the advantages of irrigation and suction for every day clinical use. The evaluation process was focused on the displacement of the medullary content and its impact on cortical perfusion. The results of the RIA reamed nailing were compared to conventional non-reamed nailing (NRN). The tibia of the sheep was used as an acute fracture model. The fracture and nailing procedure was followed by intravital staining with Procion red. The effects on cortical perfusion (Procion red staining) were addressed in polymer embedded sections and cryosections. Sudan III stained cryosections were evaluated with respect to the cortical fat distribution. After irrigation and suction minute amounts of fat were observed in the cortex, whereas after non-reamed nailing the endosteal third of the cortical bone was penetrated with fat. Non-reamed nailing acutely showed better perfusion in the endosteal tenth and periosteal third of the cortical bone, after irrigation and suction reaming perfusion was preserved to a lesser degree. Irrigation and suction significantly reduces fat intravasation, and thus the danger of system-wide damage. Therefore, the Reamer/Irrigator/Aspirator is as efficient as its experimental predecessors. PMID:21144924

  4. Adverse Reactions to Hallucinogenic Drugs.

    ERIC Educational Resources Information Center

    Meyer, Roger E. , Ed.

    This reports a conference of psychologists, psychiatrists, geneticists and others concerned with the biological and psychological effects of lysergic acid diethylamide and other hallucinogenic drugs. Clinical data are presented on adverse drug reactions. The difficulty of determining the causes of adverse reactions is discussed, as are different…

  5. Lack of deleterious effect of slow-release sodium fluoride treatment on cortical bone histology and quality in osteoporotic patients

    NASA Technical Reports Server (NTRS)

    Zerwekh, J. E.; Antich, P. P.; Sakhaee, K.; Prior, J.; Gonzales, J.; Gottschalk, F.; Pak, C. Y.

    1992-01-01

    We evaluated the effects of intermittent slow-release sodium fluoride (SRNaF) and continuous calcium citrate therapy on cortical bone histology, reflection ultrasound velocity (material strength) and back-scattered electron image analysis (BEI) in 26 osteoporotic patients before and following therapy. All measurements were made on transiliac crest bone biopsies obtained before and following 2 years of therapy in each patient. For all 26 patients there were no significant changes in cortical bone histomorphometric parameters. In 15 patients in whom bone material quality was assessed by reflection ultrasound, there was no change in velocity (4000 +/- 227 SD to 4013 +/- 240 m/s). BEI disclosed no mineralization defects or the presence of woven bone. Mean atomic number (density) of bone increased slightly, but significantly (9.261 +/- 0.311 to 9.457 +/- 0.223, P = 0.031). While these changes are less marked than those observed for cancellous bone, they indicate that this form of therapy does not adversely affect cortical bone remodelling.

  6. Essential Nutrients for Bone Health and a Review of their Availability in the Average North American Diet

    PubMed Central

    Price, Charles T; Langford, Joshua R; Liporace, Frank A

    2012-01-01

    Osteoporosis and low bone mineral density affect millions of Americans. The majority of adults in North America have insufficient intake of vitamin D and calcium along with inadequate exercise. Physicians are aware that vitamin D, calcium and exercise are essential for maintenance of bone health. Physicians are less likely to be aware that dietary insufficiencies of magnesium, silicon, Vitamin K, and boron are also widely prevalent, and each of these essential nutrients is an important contributor to bone health. In addition, specific nutritional factors may improve calcium metabolism and bone formation. It is the authors’ opinion that nutritional supplements should attempt to provide ample, but not excessive, amounts of factors that are frequently insufficient in the typical American diet. In contrast to dietary insufficiencies, several nutrients that support bone health are readily available in the average American diet. These include zinc, manganese, and copper which may have adverse effects at higher levels of intake. Some multivitamins and bone support products provide additional quantities of nutrients that may be unnecessary or potentially harmful. The purpose of this paper is to identify specific nutritional components of bone health, the effects on bone, the level of availability in the average American diet, and the implications of supplementation for each nutritional component. A summary of recommended dietary supplementation is included. PMID:22523525

  7. Bone Markers

    MedlinePlus

    ... Alkaline Phosphatase; Osteocalcin; P1NP; Procollagen Type 1 N-Terminal Propeptide Formal name: Biochemical Markers of Bone Remodeling ... tests for evaluating bone turnover: C-telopeptide (C-terminal telopeptide of type 1 collagen (CTx)) – a marker ...

  8. Bone Infections

    MedlinePlus

    ... of the body, bones can get infected. The infections are usually bacterial, but can also be fungal. ... bloodstream. People who are at risk for bone infections include those with diabetes, poor circulation, or recent ...

  9. Simulated Space Radiation and Weightlessness: Vascular-Bone Coupling Mechanisms to Preserve Skeletal Health

    NASA Technical Reports Server (NTRS)

    Alwood, J. S.; Limoli, C. L.; Delp, M. D.; Castillo, A. B.; Globus, R. K.

    2012-01-01

    Weightlessness causes a cephalad fluid shift and reduction in mechanical stimulation, adversely affecting both cortical and trabecular bone tissue in astronauts. In rodent models of weightlessness, the onset of bone loss correlates with reduced skeletal perfusion, reduced and rarified vasculature and lessened vasodilation, which resembles blood-bone symbiotic events that can occur with fracture repair and aging. These are especially serious risks for long term, exploration class missions when astronauts will face the challenge of increased exposure to space radiation and abrupt transitions between different gravity environments upon arrival and return. Previously, we found using the mouse hindlimb unloading model and exposure to heavy ion radiation, both disuse and irradiation cause an acute bone loss that was associated with a reduced capacity to produce bone-forming osteoblasts from the bone marrow. Together, these findings led us to hypothesize that exposure to space radiation exacerbates weightlessness-induced bone loss and impairs recovery upon return, and that treatment with anti-oxidants may mitigate these effects. The specific aims of this recently awarded grant are to: AIM 1 Determine the functional and structural consequences of prolonged weightlessness and space radiation (simulated spaceflight) for bone and skeletal vasculature in the context of bone cell function and oxidative stress. AIM 2 Determine the extent to which an anti-oxidant protects against weightlessness and space radiation-induced bone loss and vascular dysfunction. AIM 3 Determine how space radiation influences later skeletal and vasculature recovery from prolonged weightlessness and the potential of anti-oxidants to preserve adaptive remodeling.

  10. Bone cement

    PubMed Central

    Vaishya, Raju; Chauhan, Mayank; Vaish, Abhishek

    2013-01-01

    The knowledge about the bone cement is of paramount importance to all Orthopaedic surgeons. Although the bone cement had been the gold standard in the field of joint replacement surgery, its use has somewhat decreased because of the advent of press-fit implants which encourages bone in growth. The shortcomings, side effects and toxicity of the bone cement are being addressed recently. More research is needed and continues in the field of nanoparticle additives, enhanced bone–cement interface etc. PMID:26403875

  11. Bone Analyzer

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The danger of disuse osteoporosis under weightless condition in space led to extensive research into measurements of bone stiffness and mass by the Biomedical Research Division of Ames and Stanford University. Through its Technology Utilization Program, NASA funded an advanced SOBSA, a microprocessor-controlled bone probe system. SOBSA determines bone stiffness by measuring responses to an electromagnetic shaker. With this information, a physician can identify bone disease, measure deterioration and prescribe necessary therapy. The system is now undergoing further testing.

  12. Bone metabolism in anorexia nervosa.

    PubMed

    Fazeli, Pouneh K; Klibanski, Anne

    2014-03-01

    Anorexia nervosa (AN), a psychiatric disorder predominantly affecting young women, is characterized by self-imposed, chronic nutritional deprivation and distorted body image. AN is associated with a number of medical comorbidities including low bone mass. The low bone mass in AN is due to an uncoupling of bone formation and bone resorption, which is the result of hormonal adaptations aimed at decreasing energy expenditure during periods of low energy intake. Importantly, the low bone mass in AN is associated with a significant risk of fractures and therefore treatments to prevent bone loss are critical. In this review, we discuss the hormonal determinants of low bone mass in AN and treatments that have been investigated in this population. PMID:24419863

  13. Bone Metabolism in Anorexia Nervosa

    PubMed Central

    Fazeli, Pouneh K.; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN), a psychiatric disorder predominantly affecting young women, is characterized by self-imposed chronic nutritional deprivation and distorted body image. AN is associated with a number of medical co-morbidities including low bone mass. The low bone mass in AN is due to an uncoupling of bone formation and bone resorption, which is the result of hormonal adaptations aimed at decreasing energy expenditure during periods of low energy intake. Importantly, the low bone mass in AN is associated with a significant risk of fractures and therefore treatments to prevent bone loss are critical. In this review, we discuss the hormonal determinants of low bone mass in AN and treatments that have been investigated in this population. PMID:24419863

  14. Early and Sustained Changes in Bone Metabolism After Severe Burn Injury.

    PubMed

    Muschitz, Gabriela Katharina; Schwabegger, Elisabeth; Kocijan, Roland; Baierl, Andreas; Moussalli, Hervé; Fochtmann, Alexandra; Nickl, Stefanie; Tinhofer, Ines; Haschka, Judith; Resch, Heinrich; Rath, Thomas; Pietschmann, Peter; Muschitz, Christian

    2016-04-01

    This study investigated serum burnover marker in male patients after severe burn injury. Ongoing changes suggest alterations in bone metabolism with a likely adverse influence on bone quality and structure. PMID:26789778

  15. Bone nutrients for vegetarians.

    PubMed

    Mangels, Ann Reed

    2014-07-01

    The process of bone mineralization and resorption is complex and is affected by numerous factors, including dietary constituents. Although some dietary factors involved in bone health, such as calcium and vitamin D, are typically associated with dairy products, plant-based sources of these nutrients also supply other key nutrients involved in bone maintenance. Some research suggests that vegetarian diets, especially vegan diets, are associated with lower bone mineral density (BMD), but this does not appear to be clinically significant. Vegan diets are not associated with an increased fracture risk if calcium intake is adequate. Dietary factors in plant-based diets that support the development and maintenance of bone mass include calcium, vitamin D, protein, potassium, and soy isoflavones. Other factors present in plant-based diets such as oxalic acid and phytic acid can potentially interfere with absorption and retention of calcium and thereby have a negative effect on BMD. Impaired vitamin B-12 status also negatively affects BMD. The role of protein in calcium balance is multifaceted. Overall, calcium and protein intakes in accord with Dietary Reference Intakes are recommended for vegetarians, including vegans. Fortified foods are often helpful in meeting recommendations for calcium and vitamin D. Plant-based diets can provide adequate amounts of key nutrients for bone health. PMID:24898231

  16. SILICON AND BONE HEALTH

    PubMed Central

    JUGDAOHSINGH, R.

    2009-01-01

    Low bone mass (osteoporosis) is a silent epidemic of the 21st century, which presently in the UK results in over 200,000 fractures annually at a cost of over one billion pounds. Figures are set to increase worldwide. Understanding the factors which affect bone metabolism is thus of primary importance in order to establish preventative measures or treatments for this condition. Nutrition is an important determinant of bone health, but the effects of the individual nutrients and minerals, other than calcium, is little understood. Accumulating evidence over the last 30 years strongly suggest that dietary silicon is beneficial to bone and connective tissue health and we recently reported strong positive associations between dietary Si intake and bone mineral density in US and UK cohorts. The exact biological role(s) of silicon in bone health is still not clear, although a number of possible mechanisms have been suggested, including the synthesis of collagen and/or its stabilization, and matrix mineralization. This review gives an overview of this naturally occurring dietary element, its metabolism and the evidence of its potential role in bone health. PMID:17435952

  17. Clinical significance of HLA-DR+, CD19+, CD10+ immature B-cell phenotype and CD34+ cell detection in bone marrow lymphocytes from children affected with immune thrombocytopenic purpura.

    PubMed

    Callea, V; Comis, M; Iaria, G; Sculli, G; Morabito, F; Lombardo, V T

    1997-01-01

    In children with immune thrombocytopenic purpura (ITP), bone marrow lymphocytes can express the common acute lymphoblastic leukemia antigen (CALLA) pattern with no evidence of leukemia or lymphoma. Bone marrow lymphocytes from 23 children and 20 adults affected with ITP were studied to determine the incidence and the clinical impact of lymphocytes with the immature B-cell phenotype and CD34+ cell expression. In this investigation we identified a group consisting of 52% of the children who showed the immature B phenotype, while the remaining 48%, similarly to adult ITP displayed an increase of T-cell antigens. CD34 was positive in 53% of children, but it was present in only half of the patients with the immature B phenotype and it was always absent in adults. IgH genes disclosed a germline configuration in all six patients in the immature B phenotype group. No difference was found in the two groups of children in terms of age, presentation of the disease or final outcome. Finally, no patient in either children's group has developed an acute lymphoproliferative disorder. PMID:9299867

  18. Interaction Between Bone and Muscle in Older Persons with Mobility Limitations

    PubMed Central

    Ferrucci, L.; Baroni, M.; Ranchelli, A.; Lauretani, F.; Maggio, M.; Mecocci, P.; Ruggiero, C.

    2015-01-01

    Aging is associated with a progressive loss of bone-muscle mass and strength. When the decline in mass and strength reaches critical thresholds associated with adverse health outcomes, they are operationally considered geriatric conditions and named, respectively, osteoporosis and sarcopenia. Osteoporosis and sarcopenia share many of the same risk factors and both directly or indirectly cause higher risk of mobility limitations, falls, fractures and disability in activities of daily living. This is not surprising since bones adapt their morphology and strength to the long-term loads exerted by muscle during anti-gravitational and physical activities. Non-mechanical systemic and local factors also modulate the mechanostat effect of muscle on bone by affecting the bidirectional osteocyte-muscle crosstalk, but the specific pathways that regulate these homeostatic mechanisms are not fully understood. More research is required to reach a consensus on cut points in bone and muscle parameters that identify individuals at high risk for adverse health outcomes, including falls, fractures and disability. A better understanding of the muscle-bone physiological interaction may help to develop preventive strategies that reduce the burden of musculoskeletal diseases, the consequent disability in older persons and to limit the financial burden associated with such conditions. In this review, we summarize age-related bone-muscle changes focusing on the biomechanical and homeostatic mechanisms that explain bone-muscle interaction and we speculate about possible pathological events that occur when these mechanisms become impaired. We also report some recent definitions of osteoporosis and sarcopenia that have emerged in the literature and their implications in clinical practice. Finally, we outline the current evidence for the efficacy of available anti-osteoporotic and proposed anti-sarcopenic interventions in older persons. PMID:24050165

  19. Interaction between bone and muscle in older persons with mobility limitations.

    PubMed

    Ferrucci, L; Baroni, M; Ranchelli, A; Lauretani, F; Maggio, M; Mecocci, P; Ruggiero, C

    2014-01-01

    Aging is associated with a progressive loss of bone-muscle mass and strength. When the decline in mass and strength reaches critical thresholds associated with adverse health outcomes, they are operationally considered geriatric conditions and named, respectively, osteoporosis and sarcopenia. Osteoporosis and sarcopenia share many of the same risk factors and both directly or indirectly cause higher risk of mobility limitations, falls, fractures and disability in activities of daily living. This is not surprising since bones adapt their morphology and strength to the long-term loads exerted by muscle during anti-gravitational and physical activities. Non-mechanical systemic and local factors also modulate the mechanostat effect of muscle on bone by affecting the bidirectional osteocyte-muscle crosstalk, but the specific pathways that regulate these homeostatic mechanisms are not fully understood. More research is required to reach a consensus on cut points in bone and muscle parameters that identify individuals at high risk for adverse health outcomes, including falls, fractures and disability. A better understanding of the muscle-bone physiological interaction may help to develop preventive strategies that reduce the burden of musculoskeletal diseases, the consequent disability in older persons and to limit the financial burden associated with such conditions. In this review, we summarize age-related bone-muscle changes focusing on the biomechanical and homeostatic mechanisms that explain bone-muscle interaction and we speculate about possible pathological events that occur when these mechanisms become impaired. We also report some recent definitions of osteoporosis and sarcopenia that have emerged in the literature and their implications in clinical practice. Finally, we outline the current evidence for the efficacy of available anti-osteoporotic and proposed antisarcopenic interventions in older persons. PMID:24050165

  20. How do porosity-inducing techniques affect antibiotic elution from bone cement? An in vitro comparison between hydrogen peroxide and a mechanical mixer

    PubMed Central

    Lovric, V.; Leung, A.; Walsh, W. R.

    2008-01-01

    Background Increasing the porosity of an antibiotic-loaded cement spacer increases the antibiotic elution, but the correlation between porosity and antibiotic elution is not well documented. The purposes of this study was to attempt new porosity-increasing methods and to investigate the correlation between antibiotic elution and both total and surface porosity. Materials and methods Five types of antibiotic-loaded bone cement (ALBC) using 2 g cefazolin and 40 g cement were prepared. Other than manual mixing, hydrogen peroxide was used as a foaming agent and a mixing drill piece was used as a mechanical device to try to induce porosity when mixing the cement. Elution of antibiotic into phosphate-buffered saline was measured from 1 h to 1 week. Surface porosity was calculated from density values which were measured with a density kit and an electronic balance, while total porosity was quantified using micro-computed tomography. Results When a mixing drill piece was used to induce porosity, we observed a significant increasin antibiotic elution compared to a manually mixed ALBC. On the other hand, hydrogen peroxide reduced the elution significantly. Mild correlation between the total amount of cluted in 1 week antibiotic elution and total porosity was observed. Conclusions In terms of improving elution, the mixing drill piece seemed to be efficient. A relationship between surface porosity and elution efficacy was not observed. PMID:19384476

  1. Inducible Lentivirus-Mediated Expression of the Oct4 Gene Affects Multilineage Differentiation of Adult Human Bone Marrow-Derived Mesenchymal Stem Cells.

    PubMed

    Hao, Qiang; An, Jia-Qiang; Hao, Fei; Yang, Chun; Lu, Tao; Qu, Ting-Yu; Zhao, Li-Ru; Duan, Wei-Ming

    2015-10-01

    The octamer-binding transcription factor 4 (Oct4) gene plays an important role in maintaining the undifferentiated state of embryonic stem cells (ESCs) and reprogramming adult somatic cells into induced pluripotent stem cells (iPSCs). In the present study, we transduced human bone marrow-derived mesenchymal stem cells (hMSCs) using tetracycline-on (Tet-On) lentiviruses carrying human Oct4 to examine the effects of regulated expression of human Oct4 on the proliferation and differentiation of hMSCs. hMSCs were efficiently transduced by Tet-On lentiviruses to express regulated levels of human Oct4 with doxycycline (Dox), as examined by immunofluorescent staining, flow cytometry, and quantitative real time-PCR (qRT-PCR) assays. Ectopic expression of Oct4 in transduced hMSCs increased the ability of colony formation. Continued expression of Oct4 further enhanced adipogenic differentiation of hMSCs, and transient expression of Oct4 sufficiently enhanced osteogenic differentiation of hMSCs. qRT-PCR analysis showed that ectopic expression of Oct4 in transduced hMSCs temporally increased the expression of Sox2 and c-Myc. Interestingly, ectopic expression of Oct4 reduced neuronal differentiation of hMSCs when incubated under neuronal differentiation conditions. Our results suggest that ectopic expression of human Oct4 leads to temporal changes in multilineage differentiation of hMSCs and may inhibit neuronal differentiation of hMSCs. PMID:26230571

  2. Adverse possession of subsurface minerals

    SciTech Connect

    Bowles, P.N.

    1983-01-01

    Concepts applicable to adverse possession of subsurface minerals are generally the same as those that apply to adverse possession of all real estate. However, special requirements must be satisfied in order to perfect title to subsurface minerals by adverse possession, particularly when there has been a severance of the true title between surface and subsurface minerals. In those jurisdictions where senior and junior grants came from the state or commonwealth covering the same or some of the same land and in those areas where descriptions of land were vague or not carefully drawn, adverse possession serves to solidify land and mineral ownership. There may be some public, social, and economic justification in rewarding, with good title, those who take possession and use real estate for its intended use, including the extraction of subsurface minerals. 96 refernces.

  3. Reverse Engineering Adverse Outcome Pathways

    SciTech Connect

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  4. The science of evaluation of adverse events associated with vaccination.

    PubMed

    Halsey, Neal A

    2002-07-01

    All vaccines cause some adverse events; serious adverse events are rare. Causal associations between a vaccine and an adverse event rarely can be determined by specific tests such as identifying a vaccine agent in the affected tissue of patients. In the absence of such data, epidemiologic studies can be used to determine if the risk of the disorder is increased in vaccinated compared to unvaccinated individuals. Common mistakes include assuming a causal relationship based on a temporal association only or a series of affected patients. Careful studies have demonstrated that many hypothesized causal associations between vaccines and adverse events were not substantiated. False assumptions regarding causality are likely to occur for illnesses without a carefully defined etiology or pathogenesis. PMID:12199617

  5. Treatment with bone marrow mesenchymal stem cells combined with plumbagin alleviates spinal cord injury by affecting oxidative stress, inflammation, apoptotis and the activation of the Nrf2 pathway.

    PubMed

    Yang, Wencheng; Yang, Yan; Yang, Jian-Yi; Liang, Ming; Song, Jiangtao

    2016-04-01

    The aim of the present study was to investigate the protective effect exerted by bone marrow mesenchymal stem cells (BMSCs) in combination with plumbagin on spinal cord injury (SCI) and explore the mechanism behind this protective effect. Firstly, BMSCs were extracted from male Sprague-Dawley rats, cultured in vitro, and identified by hematoxylin. Sprague-Dawley rats were then randomly divided into a control group, SCI model group, BMSC-treated group, a plumbagin-treated group, and a BMSC and plumbagin-treated group. After treatment with BMSCs combined with plumbagin, a Basso, Beattie and Bresnahan (BBB) test was carried out and the spinal cord water content was examined in order to analyze the effect of BMSCs combined with plumbagin on SCI. The myeloperoxidase (MPO), superoxide dismutase (SOD), malondialdehyde (MDA), nuclear factor-κB (NF-κB) p65 unit, tumor necrosis factor-α (TNF-α) levels were also detected. Moreover, nuclear factor erythroid 2‑related factor 2 (Nrf2), phosphoinositide 3-kinase (PI3K), phosphorylated (p-)Akt, p-p38 mitogen-activated protein kinase (MAPK), and p-extracellular-signal-regulated kinase (ERK) protein expression levels were measured using western blot analysis. Treatment with BMSCs combined with plumbagin significantly improved locomotor recovery and reduced the spinal cord water content after SCI. The increased MPO, MDA, NF-κB p65 and TNF-α levels were significantly suppressed and the decreased SOD was significantly increased in SCI rats. The suppression of Nrf2, p-Akt and p-ERK, as well as the promotion of p-p38 MAPK, were reversed by treatment with BMSCs combined with plumbagin. These effects suggest that treatment with BMSCs combined with plumbagin alleviates SCI through its effects on oxidative stress, inflammation, apoptotis and activation of the Nrf2 pathway. PMID:26936518

  6. Biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia.

    PubMed

    Conforti, Antonella; Biagini, Simone; Del Bufalo, Francesca; Sirleto, Pietro; Angioni, Adriano; Starc, Nadia; Li Pira, Giuseppina; Moretta, Francesca; Proia, Alessandra; Contoli, Benedetta; Genovese, Silvia; Ciardi, Claudia; Avanzini, Maria Antonietta; Rosti, Vittorio; Lo-Coco, Francesco; Locatelli, Franco; Bernardo, Maria Ester

    2013-01-01

    Alterations in hematopoietic microenvironment of acute lymphoblastic leukemia patients have been claimed to occur, but little is known about the components of marrow stroma in these patients. In this study, we characterized mesenchymal stromal cells (MSCs) isolated from bone marrow (BM) of 45 pediatric patients with acute lymphoblastic leukemia (ALL-MSCs) at diagnosis (day+0) and during chemotherapy treatment (days: +15; +33; +78), the time points being chosen according to the schedule of BM aspirates required by the AIEOP-BFM ALL 2009 treatment protocol. Morphology, proliferative capacity, immunophenotype, differentiation potential, immunomodulatory properties and ability to support long-term hematopoiesis of ALL-MSCs were analysed and compared with those from 41 healthy donors (HD-MSCs). ALL-MSCs were also genetically characterized through array-CGH, conventional karyotyping and FISH analysis. Moreover, we compared ALL-MSCs generated at day+0 with those isolated during chemotherapy. Morphology, immunophenotype, differentiation potential and in vitro life-span did not differ between ALL-MSCs and HD-MSCs. ALL-MSCs showed significantly lower proliferative capacity (p<0.001) and ability to support in vitro hematopoiesis (p = 0.04) as compared with HD-MSCs, while they had similar capacity to inhibit in vitro mitogen-induced T-cell proliferation (p = N.S.). ALL-MSCs showed neither the typical translocations carried by the leukemic clone (when present), nor other genetic abnormalities acquired during ex vivo culture. Our findings indicate that ALL-MSCs display reduced ability to proliferate and to support long-term hematopoiesis in vitro. ALL-MSCs isolated at diagnosis do not differ from those obtained during treatment. PMID:24244271

  7. Biological, Functional and Genetic Characterization of Bone Marrow-Derived Mesenchymal Stromal Cells from Pediatric Patients Affected by Acute Lymphoblastic Leukemia

    PubMed Central

    Conforti, Antonella; Biagini, Simone; Del Bufalo, Francesca; Sirleto, Pietro; Angioni, Adriano; Starc, Nadia; Li Pira, Giuseppina; Moretta, Francesca; Proia, Alessandra; Contoli, Benedetta; Genovese, Silvia; Ciardi, Claudia; Avanzini, Maria Antonietta; Rosti, Vittorio; Lo-Coco, Francesco; Locatelli, Franco; Bernardo, Maria Ester

    2013-01-01

    Alterations in hematopoietic microenvironment of acute lymphoblastic leukemia patients have been claimed to occur, but little is known about the components of marrow stroma in these patients. In this study, we characterized mesenchymal stromal cells (MSCs) isolated from bone marrow (BM) of 45 pediatric patients with acute lymphoblastic leukemia (ALL-MSCs) at diagnosis (day+0) and during chemotherapy treatment (days: +15; +33; +78), the time points being chosen according to the schedule of BM aspirates required by the AIEOP-BFM ALL 2009 treatment protocol. Morphology, proliferative capacity, immunophenotype, differentiation potential, immunomodulatory properties and ability to support long-term hematopoiesis of ALL-MSCs were analysed and compared with those from 41 healthy donors (HD-MSCs). ALL-MSCs were also genetically characterized through array-CGH, conventional karyotyping and FISH analysis. Moreover, we compared ALL-MSCs generated at day+0 with those isolated during chemotherapy. Morphology, immunophenotype, differentiation potential and in vitro life-span did not differ between ALL-MSCs and HD-MSCs. ALL-MSCs showed significantly lower proliferative capacity (p<0.001) and ability to support in vitro hematopoiesis (p = 0.04) as compared with HD-MSCs, while they had similar capacity to inhibit in vitro mitogen-induced T-cell proliferation (p = N.S.). ALL-MSCs showed neither the typical translocations carried by the leukemic clone (when present), nor other genetic abnormalities acquired during ex vivo culture. Our findings indicate that ALL-MSCs display reduced ability to proliferate and to support long-term hematopoiesis in vitro. ALL-MSCs isolated at diagnosis do not differ from those obtained during treatment. PMID:24244271

  8. Bone mineral density in asthmatic patients using low dose inhaled glucocorticosteroids.

    PubMed

    El, O; Gulbahar, S; Ceylan, E; Ergor, G; Sahin, E; Senocak, O; Oncel, S; Cimrin, A

    2005-01-01

    Inhaled glucocorticosteroids are clearly beneficial in subjects with moderate or severe asthma since they are well tolerated, reduce symptoms, and improve quality of life. Some studies suggest that inhaled glucocorticosteroids can adversely affect bone mineral density. The aim of this study is to determine the effects of inhaled glucocorticosteroid therapy on bone mineral density in female patients. Forty-five asthmatic female patients (36 premenopousal and 9 postmenopausal) and forty-six healthy control subjects were included in the study. Bone mineral density was measured from lumbar spine (L1-4) and femur (neck, trochanter, and Ward's triangle) by dual energy X-Ray absorptiometry. Age, occupation, menopause and smoking status, alcohol consumption, body mass index, previous fractures, family history of fractures, menstrual history, ooferectomy, number of pregnancies, the duration of lactation, physical activity and calcium intake were questioned according to the European Vertebral Osteoporosis Study Group (EVOS) form. Cumulative inhaled glucocorticosteroid dose was calculated. T score of femoral neck and T score and bone mineral density of Ward's triangle were significantly lower in asthmatic patients compared to control group but no statistically significant correlation was found between the disease duration, inhaled steroid treatment duration, cumulative inhaled dose and annual inhaled steroid dose and bone mineral density measurement. These results suggest that in asthmatic patients using low dose inhaled corticosteroids bone mineral density is lower than in healthy controls but it is still unclear if asthma by itself is a risk factor for osteoporosis. PMID:15864884

  9. Dietary Restriction-Induced Alterations in Bone Phenotype: Effects of Lifelong Versus Short-Term Caloric Restriction on Femoral and Vertebral Bone in C57BL/6 Mice.

    PubMed

    Behrendt, Ann-Kathrin; Kuhla, Angela; Osterberg, Anja; Polley, Christian; Herlyn, Philipp; Fischer, Dagmar-Christiane; Scotland, Maike; Wree, Andreas; Histing, Tina; Menger, Michael D; Müller-Hilke, Brigitte; Mittlmeier, Thomas; Vollmar, Brigitte

    2016-04-01

    Caloric restriction (CR) is a well-described dietary intervention that delays the onset of aging-associated biochemical and physiological changes, thereby extending the life span of rodents. The influence of CR on metabolism, strength, and morphology of bone has been controversially discussed in literature. Thus, the present study evaluated whether lifelong CR versus short-term late-onset dietary intervention differentially affects the development of senile osteoporosis in C57BL/6 mice. Two different dietary regimens with 40% food restriction were performed: lifelong CR starting in 4-week-old mice was maintained for 4, 20, or 74 weeks. In contrast, short-term late-onset CR lasting a period of 12 weeks was commenced at 48 or 68 weeks of age. Control mice were fed ad libitum (AL). Bone specimens were assessed using microcomputed tomography (μCT, femur and lumbar vertebral body) and biomechanical testing (femur). Adverse effects of CR, including reduced cortical bone mineral density (Ct.BMD) and thickness (Ct.Th), were detected to some extent in senile mice (68+12w) but in particular in cortical bone of young growing mice (4+4w), associated with reduced femoral failure force (F). However, we observed a profound capacity of bone to compensate these deleterious changes of minor nutrition with increasing age presumably via reorganization of trabecular bone. Especially in lumbar vertebrae, lifelong CR lasting 20 or 74 weeks had beneficial effects on trabecular bone mineral density (Tb.BMD), bone volume fraction (BV/TV), and trabecular number (Tb.N). In parallel, lifelong CR groups showed reduced structure model index values compared to age-matched controls indicating a transformation of vertebral trabecular bone microarchitecture toward a platelike geometry. This effect was not visible in senile mice after short-term 12-week CR. In summary, CR has differential effects on cortical and trabecular bone dependent on bone localization and starting age. Our study underlines

  10. Biomechanical properties of bone allografts

    SciTech Connect

    Pelker, R.R.; Friedlaender, G.E.; Markham, T.C.

    1983-04-01

    The biomechanical properties of allograft bone can be altered by the methods chosen for its preservation and storage. These effects are minimal with deep-freezing or low-level radiation. Freeze-drying, however, markedly diminishes the torsional and bending strength of bone allografts but does not deleteriously affect the compressive or tensile strength. Irradiation of bone with more than 3.0 megarad or irradiation combined with freeze-drying appears to cause a significant reduction in breaking strength. These factors should be considered when choosing freeze-dried or irradiated allogeneic bone that will be subjected to significant loads following implantation.

  11. Bone metabolism in anorexia nervosa: molecular pathways and current treatment modalities.

    PubMed

    Howgate, D J; Graham, S M; Leonidou, A; Korres, N; Tsiridis, E; Tsapakis, E

    2013-02-01

    Eating disorders are associated with a multitude of metabolic abnormalities which are known to adversely affect bone metabolism and structure. We aimed to comprehensively review the literature on the effects of eating disorders, particularly anorexia nervosa (AN), on bone metabolism, bone mineral density (BMD), and fracture incidence. Furthermore, we aimed to highlight the risk factors and potential management strategies for patients with eating disorders and low BMD. We searched the MEDLINE/OVID (1950-July 2011) and EMBASE (1980-July 2011) databases, focussing on in vitro and in vivo studies of the effects of eating disorders on bone metabolism, bone mineral density, and fracture incidence. Low levels of estrogen, testosterone, dehydroepiandrosterone, insulin-like growth factor-1 (IGF-1), and leptin, and high levels of cortisol, ghrelin, and peptide YY (PYY) are thought to contribute to the 'uncoupling' of bone turnover in patients with active AN, leading to increased bone resorption in comparison to bone formation. Over time, this results in a high prevalence and profound degree of site-specific BMD loss in women with AN, thereby increasing fracture risk. Weight recovery and increasing BMI positively correlate with levels of IGF-1 and leptin, normalisation in the levels of cortisol, as well as markers of bone formation and resorption in both adolescent and adult patients with AN. The only treatments which have shown promise in reversing the BMD loss associated with AN include: physiologic dose transdermal and oral estrogen, recombinant human IGF-1 alone or in combination with the oral contraceptive pill, and bisphosphonate therapy. PMID:22875459

  12. Parents' Psychiatric Issues May Adversely Affect Some Children

    MedlinePlus

    ... attempted suicide, or who had struggled with antisocial personality disorder or marijuana abuse, were found to face ... and mood disorders, schizophrenia, anxiety, Alzheimer's-related dementia, personality disorders, substance abuse and attempted suicide. Parental histories ...

  13. Bone Targeted Therapies for Bone Metastasis in Breast Cancer

    PubMed Central

    Razaq, Wajeeha

    2013-01-01

    Cancer metastasis to the bone develops commonly in patients with various malignancies, and is a major cause of morbidity and diminished quality of life in many affected patients. Emerging treatments for metastatic bone disease have arisen from advances in our understanding of the unique cellular and molecular mechanisms that contribute to the bone metastasis. The tendency of cancer cells to metastasize to bone is probably the end result of many factors including vascular pathways, the highly vascular nature of the bone marrow (which increases the probability that cancer cells will be deposited in bone marrow capillaries), and molecular characteristics of the cancer cells that allow them to adapt to the bone marrow microenvironment. The goals of treating osseous metastases are manifold. Proper treatment can lead to significant improvements in pain control and function, and maintain skeletal integrity. The treatment plan requires a multidisciplinary approach. Widespread metastatic disease necessitates systemic therapy, while a localized problem is best managed with surgery, external beam radiotherapy, or both. Patients with bone metastasis can have prolonged survival, and proper management can have a significant impact on their quality of life. We will review the factors in this article that are promising molecular bone-targeted therapies or will be likely targets for future therapeutic intervention to restore bone remodeling and suppress tumor growth. PMID:26237142

  14. Cancer-associated bone disease.

    PubMed

    Rizzoli, R; Body, J-J; Brandi, M-L; Cannata-Andia, J; Chappard, D; El Maghraoui, A; Glüer, C C; Kendler, D; Napoli, N; Papaioannou, A; Pierroz, D D; Rahme, M; Van Poznak, C H; de Villiers, T J; El Hajj Fuleihan, G

    2013-12-01

    Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and

  15. Neuropsychiatric Adverse Effects of Amphetamine and Methamphetamine.

    PubMed

    Harro, Jaanus

    2015-01-01

    Administration of amphetamine and methamphetamine can elicit psychiatric adverse effects at acute administration, binge use, withdrawal, and chronic use. Most troublesome of these are psychotic states and aggressive behavior, but a large variety of undesirable changes in cognition and affect can be induced. Adverse effects occur more frequently with higher dosages and long-term use. They can subside over time but some persist long-term. Multiple alterations in the gray and white matter of the brain assessed as changes in tissue volume or metabolism, or at molecular level, have been associated with amphetamine and methamphetamine use and the psychiatric adverse effects, but further studies are required to clarify their causal role, specificity, and relationship with preceding states and traits and comorbidities. The latter include other substance use disorders, mood and anxiety disorders, attention deficit hyperactivity disorder, and antisocial personality disorder. Amphetamine- and methamphetamine-related psychosis is similar to schizophrenia in terms of symptomatology and pathogenesis, and these two disorders share predisposing genetic factors. PMID:26070758

  16. Early injury to cortical and cancellous bone from induction chemotherapy for adolescents and young adults treated for acute lymphoblastic leukemia.

    PubMed

    Orgel, E; Mueske, N M; Wren, T A L; Gilsanz, V; Butturini, A M; Freyer, D R; Mittelman, S D

    2016-04-01

    Diminished bone density and skeletal fractures are common morbidities during and following therapy for acute lymphoblastic leukemia (ALL). While cumulative doses of osteotoxic chemotherapy for ALL have been reported to adversely impact bone density, the timing of onset of this effect as well as other changes to bone structure is not well characterized. We therefore conducted a prospective cohort study in pre-adolescent and adolescent patients (10-21years) newly diagnosed with ALL (n=38) to explore leukemia-related changes to bone at diagnosis and the subsequent impact of the first phase of chemotherapy ("Induction"). Using quantitative computerized tomography (QCT), we found that pre-chemotherapy bone properties were similar to age- and sex-matched controls. Subsequently over the one month Induction period, however, cancellous volumetric bone mineral density (vBMD) decreased markedly (-26.8%, p<0.001) with sparing of cortical vBMD (tibia -0.0%, p=0.860, femur -0.7%, p=0.290). The tibia underwent significant cortical thinning (average cortical thickness-1.2%, p<0.001; cortical area-0.4%, p=0.014), while the femur was less affected. Areal BMD (aBMD) concurrently measured by dual-energy X-ray absorptiometry (DXA) underestimated changes from baseline as compared to vBMD. Biochemical evidence revealed prevalent Vitamin D insufficiency and a net resorptive state at start and end of Induction. Our findings demonstrate for the first time that significant alterations to cancellous and cortical bone develop during the first month of treatment, far earlier during ALL therapy than previously considered. Given that osteotoxic chemotherapy is integral to curative regimens for ALL, these results provide reason to re-evaluate traditional approaches toward chemotherapy-associated bone toxicity and highlight the urgent need for investigation into interventions to mitigate this common adverse effect. PMID:26851412

  17. [Bone diseases].

    PubMed

    Uebelhart, Brigitte; Rizzoli, René

    2016-01-13

    Calcium intake shows a small impact on bone mineral density and fracture risk. Denosumab is a more potent inhibitor of bone resorption than zoledronate. Abaloparatide, PTHrP analog, increases bone mineral density and decreases fracture incidence. Teriparatide could be delivered via a transdermic device. Romosozumab and odanacatib improve calculated bone strength. Sequential or combined treatments with denosumab and teriparatide could be of interest, but not denosumab followed by teriparatide. Fibrous dysplasia, Paget disease and hypophosphatasia are updated, as well as atypical femoral fracture and osteonecrosis of the jaw. PMID:26946704

  18. Implant-induced microdamage in osteoporotic bone.

    PubMed

    Yu, Zhi-Feng; Tang, Ting-Ting; Qiu, Shi-Jing

    2012-01-01

    With the increase of elderly population, more and more implant operations need to be performed in osteoporotic bone, while different forms of microdamage will be produced in peri-implant bone intraoperatively, including high- and low-density diffuse damages, as well as linear cracks. The length and location of the microcracks are the main factors in affecting the biomechanical performance of bone. Suppression of bone remodeling by bisphosphonates may lead to microdamage accumulation, which is often accompanied with the decrease of bone strength and the increase of bone fragility. Microdamage can be repaired by bone remodeling or mineralization to maintain the strength and structural integrity. Both remo- deling and mineralization can affect the bone quality and long-term implant stability. In this paper, we make a brief summary of some important issues and research progresses in this field. PMID:22480676

  19. Boning up on autophagy

    PubMed Central

    Shapiro, Irving M; Layfield, Robert; Lotz, Martin; Settembre, Carmine; Whitehouse, Caroline

    2014-01-01

    From an evolutionary perspective, the major function of bone is to provide stable sites for muscle attachment and affording protection of vital organs, especially the heart and lungs (ribs) and spinal cord (vertebrae and intervertebral discs). However, bone has a considerable number of other functions: serving as a store for mineral ions, providing a site for blood cell synthesis and participating in a complex system-wide endocrine system. Not surprisingly, bone and cartilage cell homeostasis is tightly controlled, as is the maintenance of tissue structure and mass. While a great deal of new information is accruing concerning skeletal cell homeostasis, one relatively new observation is that the cells of bone (osteoclasts osteoblasts and osteocytes) and cartilage (chondrocytes) exhibit autophagy. The focus of this review is to examine the significance of this process in terms of the functional demands of the skeleton in health and during growth and to provide evidence that dysregulation of the autophagic response is involved in the pathogenesis of diseases of bone (Paget disease of bone) and cartilage (osteoarthritis and the mucopolysaccharidoses). Delineation of molecular changes in the autophagic process is uncovering new approaches for the treatment of diseases that affect the axial and appendicular skeleton. PMID:24225636

  20. The obesity of bone

    PubMed Central

    Greco, Emanuela A.; Lenzi, Andrea; Migliaccio, Silvia

    2015-01-01

    During the last decades, obesity and osteoporosis have become important global health problems, and the belief that obesity is protective against osteoporosis has recently come into question. In fact, some recent epidemiologic and clinical studies have shown that a high level of fat mass might be a risk factor for osteoporosis and fragility fractures. Several potential mechanisms have been proposed to explain the complex relationship between adipose tissue and bone. Indeed, adipose tissue secretes various molecules, named adipokines, which are thought to have effects on metabolic, skeletal and cardiovascular systems. Moreover, fat tissue is one of the major sources of aromatase, an enzyme that synthesizes estrogens from androgen precursors, hormones that play a pivotal role in the maintenance of skeletal homeostasis, protecting against osteoporosis. Moreover, bone cells express several specific hormone receptors and recent observations have shown that bone-derived factors, such as osteocalcin and osteopontin, affect body weight control and glucose homeostasis. Thus, the skeleton is considered an endocrine target organ and an endocrine organ itself, likely influencing other organs as well. Finally, adipocytes and osteoblasts originate from a common progenitor, a pluripotential mesenchymal stem cell, which has an equal propensity for differentiation into adipocytes or osteoblasts (or other lines) under the influence of several cell-derived transcription factors. This review will highlight recent insights into the relationship between fat and bone, evaluating both potential positive and negative influences between adipose and bone tissue. It will also focus on the hypothesis that osteoporosis might be considered the obesity of bone. PMID:26623005

  1. Effects of myokines on bone.

    PubMed

    Kaji, Hiroshi

    2016-01-01

    The links between muscle and bone have been recently examined because of the increasing number of patients with osteoporosis and sarcopenia. Myokines are skeletal muscle-derived humoral cytokines and growth factors, which exert physiological and pathological functions in various distant organs, including the regulation of glucose, energy and bone metabolism. Myostatin is a crucial myokine, the expression of which is mainly limited to muscle tissues. The inhibition of myostatin signaling increases bone remodeling, bone mass and muscle mass, and it may provide a target for the treatment of both sarcopenia and osteoporosis. As myostatin is involved in osteoclast formation and bone destruction in rheumatoid arthritis, myostatin may be a target myokine for the treatment of accelerated bone resorption and joint destruction in rheumatoid arthritis. Numerous other myokines, including transforming growth factor-β, follistatin, insulin-like growth factor-I, fibroblast growth factor-2, osteoglycin, FAM5C, irisin, interleukin (IL)-6, leukemia inhibitory factor, IL-7, IL-15, monocyte chemoattractant protein-1, ciliary neurotrophic factor, osteonectin and matrix metalloproteinase 2, also affect bone cells in various manners. However, the effects of myokines on bone metabolism are largely unknown. Further research is expected to clarify the interaction between muscle and bone, which may lead to greater diagnosis and the development of the treatment for muscle and bone disorders, such as osteoporosis and sarcopenia. PMID:27579164

  2. Adverse Events Associated with Yoga: A Systematic Review of Published Case Reports and Case Series

    PubMed Central

    Cramer, Holger; Krucoff, Carol; Dobos, Gustav

    2013-01-01

    While yoga is gaining increased popularity in North America and Europe, its safety has been questioned in the lay press. The aim of this systematic review was to assess published case reports and case series on adverse events associated with yoga. Medline/Pubmed, Scopus, CAMBase, IndMed and the Cases Database were screened through February 2013; and 35 case reports and 2 case series reporting a total of 76 cases were included. Ten cases had medical preconditions, mainly glaucoma and osteopenia. Pranayama, hatha yoga, and Bikram yoga were the most common yoga practices; headstand, shoulder stand, lotus position, and forceful breathing were the most common yoga postures and breathing techniques cited. Twenty-seven adverse events (35.5%) affected the musculoskeletal system; 14 (18.4%) the nervous system; and 9 (11.8%) the eyes. Fifteen cases (19.7%) reached full recovery; 9 cases (11.3%) partial recovery; 1 case (1.3%) no recovery; and 1 case (1.3%) died. As any other physical or mental practice, yoga should be practiced carefully under the guidance of a qualified instructor. Beginners should avoid extreme practices such as headstand, lotus position and forceful breathing. Individuals with medical preconditions should work with their physician and yoga teacher to appropriately adapt postures; patients with glaucoma should avoid inversions and patients with compromised bone should avoid forceful yoga practices. PMID:24146758

  3. The use of exercise interventions to overcome adverse effects of androgen deprivation therapy.

    PubMed

    Østergren, Peter Busch; Kistorp, Caroline; Bennedbæk, Finn Noe; Faber, Jens; Sønksen, Jens; Fode, Mikkel

    2016-06-01

    Androgen deprivation therapy (ADT) induces severe hypogonadism and is associated with several adverse effects that negatively affect health and quality of life in patients with prostate cancer. ADT changes body composition characterized by an increase in fat mass and a reduction in muscle mass and strength. Insulin sensitivity is also diminished and population-based studies indicate an increased risk of diabetes mellitus and cardiovascular disease in men receiving ADT. Particularly the first 6 months of treatment seem to hold an additional risk of new cardiovascular events for patients with already existing cardiovascular disease. In this initial phase of ADT, metabolic changes are also most prominent. In addition, ADT increases the rate of bone loss and fracture risk. Currently available evidence supports the use of exercise interventions to improve physical function and mitigate ADT-induced fatigue. Some studies also indicate that exercise might moderate ADT-related changes in body composition. However, beneficial effects of exercise interventions on other ADT-related conditions have not been conclusively proven. Trials investigating the effects of ADT on fracture risk and development of diabetes mellitus and cardiovascular disease are still warranted. Furthermore, studies investigating safety and effects of physical activity in men with bone metastases are lacking. PMID:27112391

  4. Bone Metabolism in Adolescents with Anorexia Nervosa

    PubMed Central

    Misra, Madhusmita; Klibanski, Anne

    2013-01-01

    Adolescents with anorexia nervosa (AN) are at risk for low bone mass at multiple sites, associated with decreased bone turnover. Bone microarchitecture is also affected, with a decrease in bone trabecular volume and trabecular thickness, and an increase in trabecular separation. The adolescent years are typically the time when marked increases occur in bone mass accrual towards the attainment of peak bone mass, an important determinant of bone health and fracture risk in later life. AN often begins in the adolescent years, and decreased rates of bone mass accrual at this critical time are therefore also concerning for deficits in peak bone mass. Factors contributing to low bone density and decreased rates of bone accrual include alterations in body composition such as low BMI and lean body mass, and hormonal alterations such as hypogonadism, a nutritionally acquired resistance to growth hormone and low levels of IGF-1, relative hypercortisolemia, low levels of leptin, and increased adiponectin (for fat mass) and peptide YY. Therapeutic strategies include optimizing weight and menstrual recovery, and adequate calcium and vitamin D replacement. Oral estrogen-progesterone combination pills are not effective in increasing bone density in adolescents with AN. RhIGF-1 increases levels of bone formation markers in the short-term, while long-term effects remain to be determined. Bisphosphonates act by decreasing bone resorption, and are not optimal for use in adolescents with AN, in whom the primary defect is low bone formation. PMID:21301203

  5. Gravity, calcium, and bone - Update, 1989

    NASA Technical Reports Server (NTRS)

    Arnaud, Sara B.; Morey-Holton, Emily

    1990-01-01

    Recent results obtained on skeletal adaptation, calcium metabolism, and bone browth during short-term flights and ground simulated-microgravity experiments are presented. Results demonstrate that two principal components of calcium metabolism respond within days to changes in body position and to weightlessness: the calcium endocrine system and bone characteristics. Furthermore, results of recent studies imply that bone biomechanics are more severely affected by spaceflight exposures than is the bone mass.

  6. Talking Bones.

    ERIC Educational Resources Information Center

    Johnson, Jaclyn; Kassing, Sharon

    2002-01-01

    Describes cooperation with the Saint Louis Zoo to provide opportunities for elementary school students to learn about bones, how animals move, what they eat, and how much they grow. Uses biofacts which include bones, skulls, and other parts to make the laboratory a hands-on experience for students. (YDS)

  7. Bone Infections

    MedlinePlus

    ... include those with diabetes, poor circulation, or recent injury to the bone. You may also be at risk if you are having hemodialysis. Symptoms of bone infections include Pain in the infected area Chills and fever Swelling, warmth, and redness A blood ...

  8. Receptor tyrosine kinase inhibition causes simultaneous bone loss and excess bone formation within growing bone in rats

    SciTech Connect

    Nurmio, Mirja; Joki, Henna; Kallio, Jenny; Maeaettae, Jorma A.; Vaeaenaenen, H. Kalervo; Toppari, Jorma; Jahnukainen, Kirsi; Laitala-Leinonen, Tiina

    2011-08-01

    During postnatal skeletal growth, adaptation to mechanical loading leads to cellular activities at the growth plate. It has recently become evident that bone forming and bone resorbing cells are affected by the receptor tyrosine kinase (RTK) inhibitor imatinib mesylate (STI571, Gleevec (registered)) . Imatinib targets PDGF, ABL-related gene, c-Abl, c-Kit and c-Fms receptors, many of which have multiple functions in the bone microenvironment. We therefore studied the effects of imatinib in growing bone. Young rats were exposed to imatinib (150 mg/kg on postnatal days 5-7, or 100 mg/kg on postnatal days 5-13), and the effects of RTK inhibition on bone physiology were studied after 8 and 70 days (3-day treatment), or after 14 days (9-day treatment). X-ray imaging, computer tomography, histomorphometry, RNA analysis and immunohistochemistry were used to evaluate bone modeling and remodeling in vivo. Imatinib treatment eliminated osteoclasts from the metaphyseal osteochondral junction at 8 and 14 days. This led to a resorption arrest at the growth plate, but also increased bone apposition by osteoblasts, thus resulting in local osteopetrosis at the osteochondral junction. The impaired bone remodelation observed on day 8 remained significant until adulthood. Within the same bone, increased osteoclast activity, leading to bone loss, was observed at distal bone trabeculae on days 8 and 14. Peripheral quantitative computer tomography (pQCT) and micro-CT analysis confirmed that, at the osteochondral junction, imatinib shifted the balance from bone resorption towards bone formation, thereby altering bone modeling. At distal trabecular bone, in turn, the balance was turned towards bone resorption, leading to bone loss. - Research Highlights: > 3-Day imatinib treatment. > Causes growth plate anomalies in young rats. > Causes biomechanical changes and significant bone loss at distal trabecular bone. > Results in loss of osteoclasts at osteochondral junction.

  9. Boron and fish oil have different beneficial effects on strength and trabecular microarchitecture of bone.

    PubMed

    Nielsen, Forrest H; Stoecker, Barbara J

    2009-01-01

    An experiment was performed to determine whether boron deprivation would adversely affect vertebra (trabecular) bone microarchitecture, and whether any adverse effect would be modified by dietary fatty acid composition. Female rats were fed diets containing 0.1mg (9 micromol) boron/kg in a factorial arrangement with variables of supplemental boron at 0 (boron-deprived) or 3 (boron-adequate) mg (278 micromol)/kg and fat sources of 75 g safflower oil/kg or 65 g fish (menhaden)oil/kg plus 10 g linoleic acid/kg. After 6 weeks, six females per treatment were bred. Dams and pups continued on their respective diets through gestation, lactation, and after weaning. At age 21 weeks, the microarchitecture of the fourth lumbar vertebrae from 12 randomly selected pups from each treatment was determined by microcomputed tomography. Boron deprivation decreased bone volume fraction and increased trabecular separation and structural model index. Boron deprivation decreased trabecular thickness when the dietary oil was safflower. A three-point bending test for bone strength found that boron deprivation decreased the maximum force needed to break the femur. Feeding fish oil instead of safflower oil decreased connectivity density in vertebrae of boron-deficient but not in boron-adequate rats. Fish oil instead of safflower oil increased the maximum force to break and the bending moment of the femur, especially in rats fed adequate boron. The findings confirm that boron and fish oil are beneficial to cortical bone strength, and show that nutritional intakes of boron are beneficial for trabecular bone microarchitecture and influence the beneficial effects of fish oil on bone. PMID:19486829

  10. Adversity and advancing nursing knowledge.

    PubMed

    Reed, Pamela G

    2008-04-01

    This column reports the theme of adversity addressed in reference to theoretical and metatheoretical considerations for advancing nursing knowledge. The development and content of three classic nursing theories are presented by Neuman representatives, and by theorists King and Roy. Topics for continued dialogue are identified as derived from the interface between philosophy of science issues and these theories. PMID:18378823

  11. Adverse Childhood Experiences and Hallucinations

    ERIC Educational Resources Information Center

    Whitfield, C.L.; Dube, S.R.; Felitti, V.J.; Anda, R.F.

    2005-01-01

    Objective:: Little information is available about the contribution of multiple adverse childhood experiences (ACEs) to the likelihood of reporting hallucinations. We used data from the ACE study to assess this relationship. Methods:: We conducted a survey about childhood abuse and household dysfunction while growing up, with questions about health…

  12. Metastatic Bone Disease

    MedlinePlus

    ... Bone Disease cont. Page ( 4 ) MBD vs. Primary Bone Cancer The diagnosis of metastatic bone disease should not ... from an unknown primary carcinoma or a primary bone cancer (sarcoma). For example, if an area of bone ...

  13. Bone x-ray

    MedlinePlus

    ... or broken bone Bone tumors Degenerative bone conditions Osteomyelitis (inflammation of the bone caused by an infection) ... Multiple myeloma Osgood-Schlatter disease Osteogenesis imperfecta Osteomalacia Osteomyelitis Paget disease of the bone Rickets X-ray ...

  14. Adverse drug interactions with nonsteroidal anti-inflammatory drugs (NSAIDs). Recognition, management and avoidance.

    PubMed

    Johnson, A G; Seideman, P; Day, R O

    1993-02-01

    The prevalence and incidence of adverse drug interactions involving nonsteroidal anti-inflammatory drugs (NSAIDs) remains unknown. To identify those proposed drug interactions of greatest clinical significance, it is appropriate to focus on interactions between commonly used and/or commonly coprescribed drugs, interactions for which there are numerous well documented case reports in reputable journals, interactions validated by well designed in vivo human studies and those affecting high-risk drugs and/or high-risk patients. While most interactions between NSAIDs and other drugs are pharmacokinetic, NSAID-related pharmacodynamic interactions may be considerably more important in the clinical context, and prescriber ignorance is likely to be a major determinant of many adverse drug interactions. Prescribing NSAIDs is relatively contraindicated for patients on oral anticoagulants due to the risk of haemorrhage, and for patients taking high-dose methotrexate due to the dangers of bone marrow toxicity, renal failure and hepatic dysfunction. Combination NSAID therapy cannot be justified as toxicity may be increased without any improvement in efficacy. Where lithium or anti-hypertensives are coprescribed with NSAIDs, close monitoring is mandatory for lithium toxicity and hypertension, respectively, and aspirin (acetylsalicylic acid) or sulindac are preferred. Phenytoin or oral hypoglycaemic agents may be administered with NSAIDs other than pyrazoles and salicylates provided that patients are monitored carefully at the initiation and cessation of NSAID treatment. Digoxin, aminoglycosides and probenecid may be coprescribed with NSAIDs, but close monitoring is required, particularly for high-risk patients such as the elderly. Indomethacin and triamterene should be avoided due to the risk of renal failure. High dose aspirin should be replaced by naproxen in patients on valproic acid (sodium valproate) and care is required when corticosteroids are administered to patients

  15. Adverse effects of perioperative paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review.

    PubMed

    Mathiesen, O; Wetterslev, J; Kontinen, V K; Pommergaard, H-C; Nikolajsen, L; Rosenberg, J; Hansen, M S; Hamunen, K; Kjer, J J; Dahl, J B

    2014-11-01

    Post-operative pain affects millions of patients worldwide and the post-operative period has high rates of morbidity and mortality. Some of this morbidity may be related to analgesics. The aim of this review was to provide an update of current knowledge of adverse events (AE) associated with the most common perioperative non-opioid analgesics: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta-analyses of analgesic efficacy and/or adverse effects of perioperative non-opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post-operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality, cardiovascular events, surgical bleeding and renal impairment. Anastomotic leakage may be associated with NSAID usage. No firm evidence exists for an association of NSAIDs with impaired bone healing. Single-dose GCCs were not significantly related to increased infection rates or delayed wound healing. Gabapentinoid treatment was associated with increased sedation, dizziness and visual disturbances, but the clinical relevance needs clarification. Importantly, data on AEs of combinations of the above analgesics are sparse and inconclusive. Despite the potential adverse events associated with the most commonly applied non-opioid analgesics, including their combinations, reporting of such events is sparse and confined to the immediate perioperative period. Knowledge of benefit and harm related to multimodal pain treatment is deficient and needs clarification in large trials with prolonged observation. PMID:25116762

  16. Multiscale alterations in bone matrix quality increased fragility in steroid induced osteoporosis.

    PubMed

    Karunaratne, A; Xi, L; Bentley, L; Sykes, D; Boyde, A; Esapa, C T; Terrill, N J; Brown, S D M; Cox, R D; Thakker, R V; Gupta, H S

    2016-03-01

    A serious adverse clinical effect of glucocorticoid steroid treatment is secondary osteoporosis, enhancing fracture risk in bone. This rapid increase in bone fracture risk is largely independent of bone loss (quantity), and must therefore arise from degradation of the quality of the bone matrix at the micro- and nanoscale. However, we lack an understanding of both the specific alterations in bone quality n steroid-induced osteoporosis as well as the mechanistic effects of these changes. Here we demonstrate alterations in the nanostructural parameters of the mineralized fibrillar collagen matrix, which affect bone quality, and develop a model linking these to increased fracture risk in glucocorticoid induced osteoporosis. Using a mouse model with an N-ethyl-N-nitrosourea (ENU)-induced corticotrophin releasing hormone promoter mutation (Crh(-120/+)) that developed hypercorticosteronaemia and osteoporosis, we utilized in situ mechanical testing with small angle X-ray diffraction, synchrotron micro-computed tomography and quantitative backscattered electron imaging to link altered nano- and microscale deformation mechanisms in the bone matrix to abnormal macroscopic mechanics. We measure the deformation of the mineralized collagen fibrils, and the nano-mechanical parameters including effective fibril modulus and fibril to tissue strain ratio. A significant reduction (51%) of fibril modulus was found in Crh(-120/+) mice. We also find a much larger fibril strain/tissue strain ratio in Crh(-120/+) mice (~1.5) compared to the wild-type mice (~0.5), indicative of a lowered mechanical competence at the nanoscale. Synchrotron microCT show a disruption of intracortical architecture, possibly linked to osteocytic osteolysis. These findings provide a clear quantitative demonstration of how bone quality changes increase macroscopic fragility in secondary osteoporosis. PMID:26657825

  17. Multiscale alterations in bone matrix quality increased fragility in steroid induced osteoporosis

    PubMed Central

    Karunaratne, A.; Xi, L.; Bentley, L.; Sykes, D.; Boyde, A.; Esapa, C.T.; Terrill, N.J.; Brown, S.D.M.; Cox, R.D.; Thakker, R.V.; Gupta, H.S.

    2016-01-01

    A serious adverse clinical effect of glucocorticoid steroid treatment is secondary osteoporosis, enhancing fracture risk in bone. This rapid increase in bone fracture risk is largely independent of bone loss (quantity), and must therefore arise from degradation of the quality of the bone matrix at the micro- and nanoscale. However, we lack an understanding of both the specific alterations in bone quality n steroid-induced osteoporosis as well as the mechanistic effects of these changes. Here we demonstrate alterations in the nanostructural parameters of the mineralized fibrillar collagen matrix, which affect bone quality, and develop a model linking these to increased fracture risk in glucocorticoid induced osteoporosis. Using a mouse model with an N-ethyl-N-nitrosourea (ENU)-induced corticotrophin releasing hormone promoter mutation (Crh− 120/+) that developed hypercorticosteronaemia and osteoporosis, we utilized in situ mechanical testing with small angle X-ray diffraction, synchrotron micro-computed tomography and quantitative backscattered electron imaging to link altered nano- and microscale deformation mechanisms in the bone matrix to abnormal macroscopic mechanics. We measure the deformation of the mineralized collagen fibrils, and the nano-mechanical parameters including effective fibril modulus and fibril to tissue strain ratio. A significant reduction (51%) of fibril modulus was found in Crh− 120/+ mice. We also find a much larger fibril strain/tissue strain ratio in Crh− 120/+ mice (~ 1.5) compared to the wild-type mice (~ 0.5), indicative of a lowered mechanical competence at the nanoscale. Synchrotron microCT show a disruption of intracortical architecture, possibly linked to osteocytic osteolysis. These findings provide a clear quantitative demonstration of how bone quality changes increase macroscopic fragility in secondary osteoporosis. PMID:26657825

  18. Osteocyte-Driven Bone Remodeling

    PubMed Central

    Bellido, Teresita

    2013-01-01

    Osteocytes, the most abundant cells in bone, have been long postulated to detect and respond to mechanical and hormonal stimuli and to coordinate the function of osteoblasts and osteoclasts. The discovery that the inhibitor of bone formation sclerostin is primarily expressed in osteocytes in bone and it is downregulated by anabolic stimuli provided a mechanism by which osteocytes influence the activity of osteoblasts. Advances of the last few years provided experimental evidence demonstrating that osteocytes also participate in the recruitment of osteoclasts and the initiation of bone remodeling. Apoptotic osteocytes trigger yet to be identified signals that attract osteoclast precursors to specific areas of bone, which in turn differentiate to mature, bone resorbing osteoclasts. Osteocytes are also the source of molecules that regulate generation and activity of osteoclasts, such as OPG and RANKL; and genetic manipulations of the mouse genome leading to loss or gain of function, or to altered expression of either molecule in osteocytes, markedly affect bone resorption. This review highlights these investigations and discusses how the novel concept of osteocyte-driven bone resorption and formation impacts our understanding of the mechanisms by which current therapies control bone remodeling. PMID:24002178

  19. Idiosyncratic Adverse Drug Reactions: Current Concepts

    PubMed Central

    Naisbitt, Dean J.

    2013-01-01

    Idiosyncratic drug reactions are a significant cause of morbidity and mortality for patients; they also markedly increase the uncertainty of drug development. The major targets are skin, liver, and bone marrow. Clinical characteristics suggest that IDRs are immune mediated, and there is substantive evidence that most, but not all, IDRs are caused by chemically reactive species. However, rigorous mechanistic studies are very difficult to perform, especially in the absence of valid animal models. Models to explain how drugs or reactive metabolites interact with the MHC/T-cell receptor complex include the hapten and P-I models, and most recently it was found that abacavir can interact reversibly with MHC to alter the endogenous peptides that are presented to T cells. The discovery of HLA molecules as important risk factors for some IDRs has also significantly contributed to our understanding of these adverse reactions, but it is not yet clear what fraction of IDRs have a strong HLA dependence. In addition, with the exception of abacavir, most patients who have the HLA that confers a higher IDR risk with a specific drug will not have an IDR when treated with that drug. Interindividual differences in T-cell receptors and other factors also presumably play a role in determining which patients will have an IDR. The immune response represents a delicate balance, and immune tolerance may be the dominant response to a drug that can cause IDRs. PMID:23476052

  20. Bone disease in primary hypercalciuria

    PubMed Central

    Sella, Stefania; Cattelan, Catia; Realdi, Giuseppe; Giannini, Sandro

    2008-01-01

    Primary Hypercalciuria (PH) is very often accompanied with some degrees of bone demineralization. The most frequent clinical condition in which this association has been observed is calcium nephrolithiasis. In patients affected by this disorder bone density is very frequently low and increased susceptibility to fragility fractures is reported. The very poor definition of this bone disease from a histomorphometric point of view is a crucial aspect. At present, the most common finding seems to be a low bone turnover condition. Many factors are involved in the complex relationships between bone loss and PH. Since bone loss was mainly reported in patients with fasting hypercalciuria, a primary alteration in bone metabolism was proposed as a cause of both hypercalciuria and bone demineralization. This hypothesis was strengthened by the observation that some bone resorbing-cytokines, such as IL-1, IL-6, and TNF-α are high in hypercalciuric patients. The effect of an excessive response to the acid load induced by dietary protein intake seems an additional factor explaining a primitive alteration of bone. The intestine plays a major role in the clinical course of bone disease in PH. Patients with absorptive hypercalciuria less frequently show bone disease and a reduction in dietary calcium greatly increases the probability of bone loss in PH subjects. It has recently been reported that greater bone loss is associated with a larger increase in intestinal calcium absorption in PH patients. Considering the absence of PTH alterations, it was proposed that this is not a compensatory phenomenon, but probably the marker of disturbed cell calcium transport, involving both intestinal and bone tissues. While renal hypercalciuria is rather uncommon, the kidney still seems to play a role in the pathogenesis of bone loss of PH patients, possibly via the effect of mild to moderate urinary phosphate loss with secondary hypophosphatemia. In conclusion, bone loss is very common in PH

  1. Cardiovascular adverse effects of phenytoin.

    PubMed

    Guldiken, B; Rémi, J; Noachtar, Soheyl

    2016-05-01

    Phenytoin is an established drug in the treatment of acute repetitive seizures and status epilepticus. One of its main advantages over benzodiazepines is the less sedative effect. However, the possibility of cardiovascular adverse effects with the intravenous use of phenytoin cause a reluctance to its usage, and this has lead to a search for safer anticonvulsant drugs. In this study, we aimed to review the studies which evaluated the safety of phenytoin with respect to cardiovascular adverse effects. The original clinical trials and case reports listed in PUBMED in English language between the years of 1946-2014 were evaluated. As the key words, "phenytoin, diphenylhydantoin, epilepsy, seizure, cardiac toxicity, asystole, arrhythmia, respiratory arrest, hypotension, death" were used. Thirty-two clinical trials and ten case reports were identified. In the case reports, a rapid infusion rate (>50 mg/min) of phenytoin appeared as the major cause of increased mortality. In contrast, no serious cardiovascular adverse effects leading to death were met in the clinical trials which applied the recommended infusion rate and dosages. An infusion rate of 50 mg/min was reported to be safe for young patients. For old patients and patients with a cardiovascular co-morbidity, a slower infusion rate was recommended with a careful follow-up of heart rhythm and blood pressure. No cardiovascular adverse effect was reported in oral phenytoin overdoses except one case with a very high serum phenytoin level and hypoalbuminemia. Phenytoin is an effective and well tolerated drug in the treatment of epilepsy. Intravenous phenytoin is safe when given at recommended infusion rates and doses. PMID:26645393

  2. A new Fe-Mn-Si alloplastic biomaterial as bone grafting material: In vivo study

    NASA Astrophysics Data System (ADS)

    Fântânariu, Mircea; Trincă, Lucia Carmen; Solcan, Carmen; Trofin, Alina; Strungaru, Ştefan; Şindilar, Eusebiu Viorel; Plăvan, Gabriel; Stanciu, Sergiu

    2015-10-01

    Designing substrates having suitable mechanical properties and targeted degradation behavior is the key's development of bio-materials for medical application. In orthopedics, graft material may be used to fill bony defects or to promote bone formation in osseous defects created by trauma or surgical intervention. Incorporation of Si may increase the bioactivity of implant locally, both by enhancing interactions at the graft-host interface and by having a potential endocrine like effect on osteoblasts. A Fe-Mn-Si alloy was obtained as alloplastic graft materials for bone implants that need long recovery time period. The surface morphology of the resulted specimens was investigated using scanning electrons microscopy (VegaTescan LMH II, SE detector, 30 kV), X-ray diffractions (X'Pert equipment) or X-ray dispersive energy analyze (Bruker EDS equipment). This study objective was to evaluate in vivo the mechanisms of degradation and the effects of its implantation over the main metabolic organs. Biochemical, histological, plain X radiography and computed tomography investigations showed good compatibility of the subcutaneous implants in the rat organism. The implantation of the Fe-Mn-Si alloy, in critical size bone (tibiae) defect rat model, did not induced adverse biological reactions and provided temporary mechanical support to the affected bone area. The biodegradation products were hydroxides layers which adhered to the substrate surface. Fe-Mn-Si alloy assured the mechanical integrity in rat tibiae defects during bone regeneration.

  3. Maturation of bone and dentin matrices in rats flown on the Soviet biosatellite Cosmos 1887

    NASA Technical Reports Server (NTRS)

    Simmons, D. J.; Grynpas, M. D.; Rosenberg, G. D.

    1990-01-01

    We have studied the chemistry, hydroxyapatite crystal size, and maturational changes in bone and dentin from rats exposed to microgravity for 12 days in a Soviet biosatellite (Cosmos 1887). Bone ash was reduced in vertebrae (L5) but not in the non-weight-bearing calvaria or mandibles. All tissues had a relatively normal percentage composition of Ca, P, and Mg. Nevertheless, flight rat calvaria and vertebral tissues tended to exhibit lower Ca/P and higher Ca/Mg ratios that any of their weight-matched controls groups, and gradient density analysis (calvaria) indicated a strong shift to the fractions lower specific gravity that was commensurate with impaired rates of matrix-mineral maturation. X-ray diffraction data were confirmatory. Bone hydroxyapatite crystal growth in the mandibles of flight rats was preferentially altered in such a way as to reduce their size (C-axis dimension). But in the mandibular diastemal region devoid of muscle attachments, flight rat bone and dentin were normal with respect to the Ca, P, Mg, and Zn concentrations and Ca/P and Ca/Mg ratios of age-matched controls. These observations affirm the concept that while microgravity most adversely affects the maturation of newly formed matrix and mineral moieties in weight-bearing bone, such effects occur throughout the skeleton.

  4. 3-dimensional microscope analysis of bone and tooth surface modifications: comparisons of fossil specimens and replicas.

    PubMed

    Bello, Silvia M; Verveniotou, Efstratia; Cornish, Lorraine; Parfitt, Simon A

    2011-01-01

    Cut-marks on fossil bones and teeth are an important source of evidence in the reconstruction of ancient butchery practices. The analysis of butchery marks has allowed archaeologists to interpret aspects of past subsistence strategies and the behavior of early humans. Recent advances in optical scanning microscopy allow detailed measurements of cut-mark morphology to be undertaken. An example of this technology is the Alicona 3D InfiniteFocus imaging microscope, which has been applied recently to the study of surface modifications on bones and teeth. Three-dimensional models generated by the Alicona microscope have been used to identify cross-sectional features of experimental cut-marks that are characteristic for specific cutting actions (e.g., slicing, chopping, scraping) and different tool types (e.g., metal versus stone tools). More recently, this technology has been applied successfully to the analysis of ∼500,000 year-old cut-marked animal bones from Boxgrove (U.K.), as well as cannibalized 14,700 cal BP year-old human bones from Gough's Cave (U.K.). This article describes molding methods used to replicate fragile prehistoric bones and teeth, where image quality was adversely affected by specimen translucency and reflectivity. Alicona images generated from molds and casts are often of better quality than those of the original specimen. PMID:21660994

  5. [Adverse events of psychotropic drugs].

    PubMed

    Watanabe, Koichiro; Kikuchi, Toshiaki

    2014-01-01

    The authors discuss adverse events which are often missed but clinicians should pay attention to in order to preserve patients'quality of life(QOL). Among mood stabilizers, lithium may cause a urinary volume increase, hyperparathyroidism, and serum calcium elevation; sodium valproate possibly increases androgenic hormone levels and the risk of polycystic ovary syndrome (PCOS) as well as hypothyroidism. Moreover, in addition to teratogenesis, it has been reported that fetal exposure to a higher dose of valproate is associated with a lower intelligence quotient and higher incidence of autism spectrum disorders in children. Antidepressants with a higher affinity for serotonin transporters might induce gastrointestinal bleeding, and some antidepressants cause sexual dysfunction more frequently than others. Activation syndrome is still a key side effect which should be noted. Regarding the adverse events of antipsychotics, subjective side effects unpleasant to patients such as dysphoria and a lower subjective well-being should not be overlooked. We clinicians have to cope with adverse events worsening the QOL of patients with psychiatric disorders and, therefore, we need to adopt appropriate counter-measures. PMID:24864567

  6. Pharmacogenetics of idiosyncratic adverse drug reactions.

    PubMed

    Pirmohamed, Munir

    2010-01-01

    Idiosyncratic adverse drug reactions are unpredictable and thought to have an underlying genetic etiology. With the completion of the human genome and HapMap projects, together with the rapid advances in genotyping technologies, we have unprecedented capabilities in identifying genetic predisposing factors for these relatively rare, but serious, reactions. The main roadblock to this is the lack of sufficient numbers of well-characterized samples from patients with such reactions. This is now beginning to be solved through the formation of international consortia, including developing novel ways of identifying and recruiting patients affected by these reactions, both prospectively and retrospectively. This has been led by the research on abacavir hypersensitivity - its association with HLA-B*5701 forms the gold standard of how we need to identify associations and implement them in clinical practice. Strong genetic predisposing factors have also been identified for hypersensitivity reactions such as are associated with carbamazepine, allopurinol, flucloxacillin, and statin-induced myopathy. However, for most other idiosyncratic adverse drug reactions, the genetic effect sizes have been low to moderate, although this may partly be due to the fact that only small numbers have been investigated and limited genotyping strategies have been utilized. It may also indicate that genetic predisposition will be dependent on multiple genes, with complex interactions with environmental factors. Irrespective of the strength of the genetic associations identified with individual idiosyncratic adverse drug reactions, it is important to undertake functional investigations to provide insights into the mechanism(s) of how the drug interacts with the gene variant to lead to a phenotype, which can take a multitude of clinical forms with variable severity. Such investigations will be essential in preventing the burden caused by idiosyncratic reactions, both in healthcare and in industry

  7. Six-year trajectories of post-traumatic stress and severe psychological distress symptoms and associations with timing of trauma exposure, ongoing adversity and sense of injustice: a latent transition analysis of a community cohort in conflict-affected Timor-Leste

    PubMed Central

    Rees, S; Steel, Z; Tam, N; Soares, Z; Soares, C; Silove, DM

    2016-01-01

    Objectives To identify the 6-year trajectories of post-traumatic stress symptoms (PTSS) and psychological distress symptoms, and examine for associations with timing of trauma exposure, ongoing adversity and with the sense of injustice in conflict-affected Timor-Leste. Setting A whole-of-household survey was conducted in 2004 and 2010 in Dili, the capital of Timor-Leste. Participants 1022 adults were followed up over 6 years (retention rate 84.5%). Interviews were conducted by field workers applying measures of traumatic events (TEs), ongoing adversity, a sense of injustice, PTS symptoms and psychological distress. Results Latent transition analysis supported a 3-class longitudinal model (psychological distress, comorbid symptoms and low symptoms). We derived 4 composite trajectories comprising recovery (20.8%), a persisting morbidity trajectory (7.2%), an incident trajectory (37.2%) and a low-symptom trajectory (34.7%). Compared with the low-symptom trajectory, the persistent and incident trajectories reported greater stress arising from poverty and family conflict, higher TE exposure for 2 historical periods, and a sense of injustice for 2 historical periods. The persistent trajectory was unique in reporting greater TE exposure in the Indonesian occupation, whereas the incident trajectory reported greater TE exposure during the later internal conflict that occurred between baseline and follow-up. Compared with the low-symptom trajectory, the incident trajectory reported a greater sense of injustice relating to the periods of the Indonesian occupation and independence. The persistent trajectory was characterised by a sense of injustice relating to the internal conflict and contemporary times. The recovery trajectory was characterised by the absence of these risk factors, the only difference from the low-symptom trajectory being that the former reported a sense of injustice for the period surrounding independence. Conclusions Our findings suggest that the timing

  8. Metal-on-Metal Hip Arthroplasty: A Review of Adverse Reactions and Patient Management.

    PubMed

    Drummond, James; Tran, Phong; Fary, Camdon

    2015-01-01

    Recent alarming joint registry data highlighting increased revision rates has prompted further research into the area of metal-on-metal hip replacements and resurfacings. This review article examines the latest literature on the topic of adverse reactions to metal debris and summarises the most up-to-date guidelines on patient management. Adverse reactions to metal debris can cause significant damage to soft tissue and bone if not diagnosed early. Furthermore, not every patient with an adverse reaction to metal debris will be symptomatic. As such, clinicians must remain vigilant when assessing and investigating these patients in order to detect failing implants and initiate appropriate management. PMID:26132653

  9. Drugs that may harm bone: Mitigating the risk.

    PubMed

    Hant, Faye N; Bolster, Marcy B

    2016-04-01

    Glucocorticoids, proton pump inhibitors, selective serotonin reuptake inhibitors (SSRIs), certain antiepileptic drugs, and aromatase inhibitors have significant adverse effects on bone. Healthcare providers should monitor the bone health of patients on these agents, supplement their intake of calcium and vitamin D, encourage weight-bearing exercise, and initiate osteoporosis-prevention treatment as indicated. PMID:27055202

  10. Caffeine inhibits the viability and osteogenic differentiation of rat bone marrow-derived mesenchymal stromal cells

    PubMed Central

    Zhou, Y; Guan, XX; Zhu, ZL; Guo, J; Huang, YC; Hou, WW; Yu, HY

    2010-01-01

    BACKGROUND AND PURPOSE Caffeine is consumed extensively in Europe and North America. As a risk factor for osteoporosis, epidemiological studies have observed that caffeine can decrease bone mineral density, adversely affect calcium absorption and increase the risk of bone fracture. However, the exact mechanisms have not been fully investigated. Here, we examined the effects of caffeine on the viability and osteogenesis of rat bone marrow-derived mesenchymal stromal cells (rBMSCs). EXPERIMENTAL APPROACH Cell viability, apoptosis and necrosis were quantified using thymidine incorporation and flow cytometry. Sequential gene expressions in osteogenic process were measured by real-time PCR. cAMP, alkaline phosphatase and osteocalcin were assessed by immunoassay, spectrophotometry and radioimmunoassay, respectively. Mineralization was determined by calcium deposition. KEY RESULTS After treating BMSCs with high caffeine concentrations (0.1–1 mM), their viability decreased in a concentration-dependent manner. This cell death was primarily due to necrosis and, to a small extent, apoptosis. Genes and protein sequentially expressed in osteogenesis, including Cbfa1/Runx2, collagen I, alkaline phosphatase and its protein, were significantly downregulated except for osteocalcin and its protein. Moreover, caffeine inhibited calcium deposition in a concentration- and time-dependent manner, but increased intracellular cAMP in a concentration-dependent manner. CONCLUSIONS AND IMPLICATIONS By suppressing the commitment of BMSCs to the osteogenic lineage and selectively inhibiting gene expression, caffeine downregulated some important events in osteogenesis and ultimately affected bone mass. PMID:20726981

  11. The relationship between blood lead levels and periodontal bone loss in the United States, 1988-1994.

    PubMed Central

    Dye, Bruce A; Hirsch, Rosemarie; Brody, Debra J

    2002-01-01

    An association between bone disease and bone lead has been reported. Studies have suggested that lead stored in bone may adversely affect bone mineral metabolism and blood lead (PbB) levels. However, the relationship between PbB levels and bone loss attributed to periodontal disease has never been reported. In this study we examined the relationship between clinical parameters that characterize bone loss due to periodontal disease and PbB levels in the U.S. population. We used data from the Third National Health and Nutritional Examination Survey (NHANES III), 1988-1994, for the analyses. A total of 10,033 participants 20-69 years of age who completed a periodontal examination and had whole blood tested for lead were examined. Four types of periodontal disease measures were used to indicate oral bone loss: periodontal pocket depth, attachment loss extent, attachment loss severity, and the presence of dental furcations. We found that dental furcations were the best periodontal bone loss indicator for PbB levels (p = 0.005) in a multivariate linear regression model adjusting for sex, age, race/ethnicity, educational attainment, poverty status, smoking, and age of home. Furthermore, after additional modeling, we found a smoking and dental furcation interaction (p = 0.034). Subsequent stratified analyses indicated that current and past smoking is an effect modifier for dental furcations on PbB levels. These findings indicate that increased PbB levels may be associated with advanced periodontal bone loss, particularly among people with a history of smoking. PMID:12361924

  12. 15 CFR 970.701 - Significant adverse environmental effects.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... under a license of scale-model mining systems which simulate commercial recovery could adversely affect... setting of instruments; (7) Sampling by box core, small diameter core or grab sampler, to determine seabed... mining tests under exploration licenses will be extremely small. (ii) Blanketing of benthic fauna...

  13. 15 CFR 970.701 - Significant adverse environmental effects.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... under a license of scale-model mining systems which simulate commercial recovery could adversely affect... setting of instruments; (7) Sampling by box core, small diameter core or grab sampler, to determine seabed... mining tests under exploration licenses will be extremely small. (ii) Blanketing of benthic fauna...

  14. Detecting Adverse Events Using Information Technology

    PubMed Central

    Bates, David W.; Evans, R. Scott; Murff, Harvey; Stetson, Peter D.; Pizziferri, Lisa; Hripcsak, George

    2003-01-01

    Context: Although patient safety is a major problem, most health care organizations rely on spontaneous reporting, which detects only a small minority of adverse events. As a result, problems with safety have remained hidden. Chart review can detect adverse events in research settings, but it is too expensive for routine use. Information technology techniques can detect some adverse events in a timely and cost-effective way, in some cases early enough to prevent patient harm. Objective: To review methodologies of detecting adverse events using information technology, reports of studies that used these techniques to detect adverse events, and study results for specific types of adverse events. Design: Structured review. Methodology: English-language studies that reported using information technology to detect adverse events were identified using standard techniques. Only studies that contained original data were included. Main Outcome Measures: Adverse events, with specific focus on nosocomial infections, adverse drug events, and injurious falls. Results: Tools such as event monitoring and natural language processing can inexpensively detect certain types of adverse events in clinical databases. These approaches already work well for some types of adverse events, including adverse drug events and nosocomial infections, and are in routine use in a few hospitals. In addition, it appears likely that these techniques will be adaptable in ways that allow detection of a broad array of adverse events, especially as more medical information becomes computerized. Conclusion: Computerized detection of adverse events will soon be practical on a widespread basis. PMID:12595401

  15. Assessment of bone turnover and bone quality in type 2 diabetic bone disease: current concepts and future directions.

    PubMed

    Rubin, Mishaela R; Patsch, Janina M

    2016-01-01

    Substantial evidence exists that in addition to the well-known complications of diabetes, increased fracture risk is an important morbidity. This risk is probably due to altered bone properties in diabetes. Circulating biochemical markers of bone turnover have been found to be decreased in type 2 diabetes (T2D) and may be predictive of fractures independently of bone mineral density (BMD). Serum sclerostin levels have been found to be increased in T2D and appear to be predictive of fracture risk independent of BMD. Bone imaging technologies, including trabecular bone score (TBS) and quantitative CT testing have revealed differences in diabetic bone as compared to non-diabetic individuals. Specifically, high resolution peripheral quantitative CT (HRpQCT) imaging has demonstrated increased cortical porosity in diabetic postmenopausal women. Other factors such as bone marrow fat saturation and advanced glycation endproduct (AGE) accumulation might also relate to bone cell function and fracture risk in diabetes. These data have increased our understanding of how T2D adversely impacts both bone metabolism and fracture risk. PMID:27019762

  16. Assessment of bone turnover and bone quality in type 2 diabetic bone disease: current concepts and future directions

    PubMed Central

    Rubin, Mishaela R; Patsch, Janina M

    2016-01-01

    Substantial evidence exists that in addition to the well-known complications of diabetes, increased fracture risk is an important morbidity. This risk is probably due to altered bone properties in diabetes. Circulating biochemical markers of bone turnover have been found to be decreased in type 2 diabetes (T2D) and may be predictive of fractures independently of bone mineral density (BMD). Serum sclerostin levels have been found to be increased in T2D and appear to be predictive of fracture risk independent of BMD. Bone imaging technologies, including trabecular bone score (TBS) and quantitative CT testing have revealed differences in diabetic bone as compared to non-diabetic individuals. Specifically, high resolution peripheral quantitative CT (HRpQCT) imaging has demonstrated increased cortical porosity in diabetic postmenopausal women. Other factors such as bone marrow fat saturation and advanced glycation endproduct (AGE) accumulation might also relate to bone cell function and fracture risk in diabetes. These data have increased our understanding of how T2D adversely impacts both bone metabolism and fracture risk. PMID:27019762

  17. Bone marrow transplant

    MedlinePlus

    Transplant - bone marrow; Stem cell transplant; Hematopoietic stem cell transplant; Reduced intensity nonmyeloablative transplant; Mini transplant; Allogenic bone marrow transplant; Autologous bone marrow transplant; ...

  18. Bone marrow transplant

    MedlinePlus

    Transplant - bone marrow; Stem cell transplant; Hematopoietic stem cell transplant; Reduced intensity, nonmyeloablative transplant; Mini transplant; Allogenic bone marrow transplant; Autologous bone marrow transplant; Umbilical ...

  19. Experiment K305: Quantitative analysis of selected bone parameters

    NASA Technical Reports Server (NTRS)

    Wrongski, T. J.; Morey-Holton, E.; Cann, C. E.; Arnaud, C. D.; Baylink, D. J.; Turner, R. T.; Jee, W. S. S.

    1981-01-01

    The skeletal alterations induced by space flight were determined to be a reduced rate of periosteal bone formation in tibial and humeral diaphyses, a decreased trabecular bone volume, and an increased fat content of the bone marrow in the proximal tibial metaphysis. An increased incidence of arrest lines in flight animals suggested that periosteal bone formation may have ceased during space flight. Endosteal bone resorption was not affected markedly.

  20. Metabolic Bone Disease in Primary Biliary Cirrhosis.

    PubMed

    Glass, Lisa M; Su, Grace Li-Chun

    2016-06-01

    Primary biliary cirrhosis (PBC) is a liver-specific autoimmune disease that primarily affects women (female-to-male ratio, 10:1) between 40 and 60 years of age. Metabolic bone disease is a common complication of PBC, affecting 14% to 52% of patients, depending on the duration and severity of liver disease. The osteoporosis seen in PBC seems mainly due to low bone formation, although increased bone resorption may contribute. Treatment of osteoporosis consists primarily of antiresorptive agents. Additional large prospective, long-term studies in patients with PBC are needed to determine efficacy in improving bone density as well as reducing fracture risk. PMID:27261902

  1. Ultrastructural changes during the fatigue of bone

    NASA Astrophysics Data System (ADS)

    Kohn, David H.

    2006-07-01

    Repetitive mechanical loading of bone can lead to ultrastructural-level damage, which can lead to fracture if not repaired. Skeletal fractures result not only from a loss in bone mass, but also because of alterations in tissue quality. Therefore, it is important to also delineate how changes in tissue ultrastructure affect the mechanistic response of bone to its physical environment. In this overview, factors affecting tissue quality, in particular fatigue resistance, are reviewed, followed by examples of recent work that has identified ultrastructural and compositional changes that occur in bone during fatigue.

  2. Cutaneous Adverse Effects of Neurologic Medications.

    PubMed

    Bahrani, Eman; Nunneley, Chloe E; Hsu, Sylvia; Kass, Joseph S

    2016-03-01

    Life-threatening and benign drug reactions occur frequently in the skin, affecting 8 % of the general population and 2-3 % of all hospitalized patients, emphasizing the need for physicians to effectively recognize and manage patients with drug-induced eruptions. Neurologic medications represent a vast array of drug classes with cutaneous side effects. Approximately 7 % of the United States (US) adult population is affected by adult-onset neurological disorders, reflecting a large number of patients on neurologic drug therapies. This review elucidates the cutaneous reactions associated with medications approved by the US Food and Drug Administration (FDA) to treat the following neurologic pathologies: Alzheimer disease, amyotrophic lateral sclerosis, epilepsy, Huntington disease, migraine, multiple sclerosis, Parkinson disease, and pseudobulbar affect. A search of the literature was performed using the specific FDA-approved drug or drug classes in combination with the terms 'dermatologic,' 'cutaneous,' 'skin,' or 'rash.' Both PubMed and the Cochrane Database of Systematic Reviews were utilized, with side effects ranging from those cited in randomized controlled trials to case reports. It behooves neurologists, dermatologists, and primary care physicians to be aware of the recorded cutaneous adverse reactions and their severity for proper management and potential need to withdraw the offending medication. PMID:26914914

  3. Mechanistic fracture criteria for the failure of human cortical bone

    SciTech Connect

    Nalla, Ravi K.; Kinney, John H.; Ritchie, Robert O.

    2002-12-13

    A mechanistic understanding of fracture in human bone is critical to predicting fracture risk associated with age and disease. Despite extensive work, a mechanistic framework for describing how the underlying microstructure affects the failure mode in bone is lacking.

  4. What Are the Risk Factors for Bone Cancer?

    MedlinePlus

    ... bone cancer? What are the risk factors for bone cancer? A risk factor is anything that affects your ... are caused by defects (mutations) in certain genes. Osteosarcomas Children with certain rare inherited syndromes have an ...

  5. [Adverse ocular effects of vaccinations].

    PubMed

    Ness, T; Hengel, H

    2016-07-01

    Vaccinations are very effective measures for prevention of infections but are also associated with a long list of possible side effects. Adverse ocular effects following vaccination have been rarely reported or considered to be related to vaccinations. Conjunctivitis is a frequent sequel of various vaccinations. Oculorespiratory syndrome and serum sickness syndrome are considered to be related to influenza vaccinations. The risk of reactivation or initiation of autoimmune diseases (e. g. uveitis) cannot be excluded but has not yet been proven. Overall the benefit of vaccination outweighs the possible but very low risk of ocular side effects. PMID:27357302

  6. Adverse Effects of Electroconvulsive Therapy.

    PubMed

    Andrade, Chittaranjan; Arumugham, Shyam Sundar; Thirthalli, Jagadisha

    2016-09-01

    Electroconvulsive therapy (ECT) is an effective treatment commonly used for depression and other major psychiatric disorders. We discuss potential adverse effects (AEs) associated with ECT and strategies for their prevention and management. Common acute AEs include headache, nausea, myalgia, and confusion; these are self-limiting and are managed symptomatically. Serious but uncommon AEs include cardiovascular, pulmonary, and cerebrovascular events; these may be minimized with screening for risk factors and by physiologic monitoring. Although most cognitive AEs of ECT are short-lasting, troublesome retrograde amnesia may rarely persist. Modifications of and improvements in treatment techniques minimize cognitive and other AEs. PMID:27514303

  7. [Changes in bones in the aging males].

    PubMed

    Grzegorzewska, Alicja E

    2007-08-01

    The report contains a summary of results on bone changes in aging male, presented during the 2nd CSSAM/ISAM North American Congress on the Aging Male. It was shown that age-related osteoporosis can be slowed in men by substitutive treatment with testosterone. Taking into account such therapy, one should remember about its adverse effects. PMID:18044351

  8. Effect of altered reproductive function and lowered testosterone levels on bone density in male endurance athletes

    PubMed Central

    Bennell, Kim L; Brukner, Peter D; Malcolm, Susan A

    1996-01-01

    The effect of intense physical activity on female reproductive hormones is well recognised1–3 and there is evidence that menstrual disturbances associated with hypo-oestrogenism adversely affect bone density especially at the lumbar spine.4 5 Physical activity can also have a range of effects on male reproductive function depending upon the intensity and duration of the activity and the fitness of the individual.6 In particular, endurance training may be associated with reductions in circulating testosterone levels. Since testosterone has important anabolic roles, alterations in reproductive hormone profiles may have detrimental skeletal consequences similar to those seen in females with menstrual disturbances. The aim of this brief review is to present the limited literature on the relation between bone density and testosterone levels in male endurance athletes. PMID:8889111

  9. Depression, Antidepressants and Bone Health in Older Adults: A Systematic Review

    PubMed Central

    Gebara, Marie Anne; Shea, Marcie L.O.; Lipsey, Kim L; Teitelbaum, Steven L.; Civitelli, Roberto; Müller, Daniel J.; Reynolds, Charles F.; Mulsant, Benoit H.; Lenze, Eric J.

    2014-01-01

    Objectives Some studies have reportedan association between depression or serotonin reuptake inhibitor (SRI) antidepressant use and osteoporosis. This association raises concern about the widespread use of antidepressants in older adults and suggests the need to reevaluate this practice. This review examines the association of both depression and antidepressant use with bone health in older adults and the implications for treatment. Design A systematic review of studies of the association between depression or antidepressants and bone health in older adults. Setting All studies that measured depression or antidepressant exposure and bone mineral density (BMD). Participants Adults aged 60 and above. Measurements Age, site of BMD measurement by dual-energy x-ray absorptiometry (DXA), measure of depression or depressive symptoms, association between BMD changes and depression or antidepressant use. Results Nineteen observational studies met the final inclusion criteria; no experimental studies were found. Several cross-sectional and longitudinal studies found that depression or depressive symptoms were associated with decreased BMD. Few studies and only two longitudinal studies addressed the association between SRI antidepressant use and a decrease in BMD and they had conflicting results. Conclusion Depression and depressive symptoms are associated with decreased bone mass and accelerated bone loss in older adults; putative mechanisms underlying this relationship are discussed. There is insufficient evidence that SRI antidepressants adversely affect bone health.Thus, a change in current recommendations for the use of antidepressants in older adults is not justified at the present time. Given the high public health significance of this question, more studies are required to determine whether (and in whom) antidepressants may be deleterious for bone health. PMID:25039259

  10. Adverse drug reactions in dermatology.

    PubMed

    Ferner, R E

    2015-03-01

    Adverse drug reactions (ADRs) - that is, unintended and harmful responses to medicines - are important to dermatologists because many present with cutaneous signs and because dermatological treatments can cause serious ADRs. The detection of ADRs to new drugs is often delayed because they have a long latency or are rare or unexpected. This means that ADRs to newer agents emerge only slowly after marketing. ADRs are part of the differential diagnosis of unusual rashes. A good drug history that includes details of drug dose, time-course of the reaction and factors that may make the patient more susceptible, will help. For example, Stevens-Johnson syndrome with abacavir is much commoner in patients with HLA-B*5701, and has a characteristic time course. Newer agents have brought newer reactions; for example, acneiform rashes associated with epidermal growth factor receptor inhibitors such as erlotinib. Older systemic agents used to treat skin disease, including corticosteroids and methotrexate, cause important ADRs. The adverse effects of newer biological agents used in dermatology are becoming clearer; for example, hypersensitivity reactions or loss of efficacy from antibody formation and progressive multifocal leucoencephalopathy due to reactivation of latent JC (John Cunningham) virus infections during efalizumab treatment. Unusual or serious harm from medicines, including ADRs, medication errors and overdose, should be reported. The UK Yellow Card scheme is online, and patients can report their own ADRs. PMID:25622648

  11. [Recipients adverse reactions: guidance supports].

    PubMed

    Bazin, A

    2010-12-01

    Since 1994, adverse effects of transfusion transmitted to the French haemovigilance network are registered on "e-fit", the database of the French agency for the safety of health products (Afssaps). In order to improve their analysis, guidance supports have been made by Afssaps working groups. Each support deals with a blood transfusion side effect and is composed of five parts including pathophysiological mechanisms, diagnostic criteria, management recommendations, etiologic investigations and rules of filing the notification form on e-fit. The major characteristics of sheets published or soon-to-be published are presented: transfusion-related acute lung injury, transfusion-transmitted bacterial infection, non-haemolytic febrile reaction, allergic reaction, transfusion-associated circulatory overload, hypotensive transfusion reaction, alloimmunization, erythrocyte incompatibility reaction and hemosiderosis. These new supports give relevant guidelines allowing a better analysis and evaluation of recipients' adverse reactions, particularly their diagnosis, gravity and accountability. They could also initiate studies in European and international haemovigilance and transfusion networks. PMID:21051267

  12. Adverse effects of plasma transfusion.

    PubMed

    Pandey, Suchitra; Vyas, Girish N

    2012-05-01

    Plasma utilization has increased over the past two decades, and there is a growing concern that many plasma transfusions are inappropriate. Plasma transfusion is not without risk, and certain complications are more likely with plasma than other blood components. Clinical and laboratory investigations of the patients suffering reactions after infusion of fresh-frozen plasma (FFP) define the etiology and pathogenesis of the panoply of adverse effects. We review here the pathogenesis, diagnosis, and management of the risks associated with plasma transfusion. Risks commonly associated with FFP include: 1) transfusion-related acute lung injury, 2) transfusion-associated circulatory overload, and 3) allergic and/or anaphylactic reactions. Other less common risks include 1) transmission of infections, 2) febrile nonhemolytic transfusion reactions, 3) red blood cell alloimmunization, and 4) hemolytic transfusion reactions. The effects of pathogen inactivation or reduction methods on these risks are also discussed. Fortunately, a majority of the adverse effects are not lethal and are adequately treated in clinical practice. PMID:22578374

  13. Using Micro-CT Derived Bone Microarchitecture to Analyze Bone Stiffness - A Case Study on Osteoporosis Rat Bone.

    PubMed

    Wu, Yuchin; Adeeb, Samer; Doschak, Michael R

    2015-01-01

    Micro-computed tomography (Micro-CT) images can be used to quantitatively represent bone geometry through a range of computed attenuation-based parameters. Nonetheless, those parameters remain indirect indices of bone microarchitectural strength and require further computational tools to interpret bone structural stiffness and potential for mechanical failure. Finite element analysis (FEA) can be applied to measure trabecular bone stiffness and potentially predict the location of structural failure in preclinical animal models of osteoporosis, although that procedure from image segmentation of Micro-CT derived bone geometry to FEA is often challenging and computationally expensive, resulting in failure of the model to build. Notably, the selection of resolution and threshold for bone segmentation are key steps that greatly affect computational complexity and validity. In the following study, we evaluated an approach whereby Micro-CT derived grayscale attenuation and segmentation data guided the selection of trabecular bone for analysis by FEA. We further correlated those FEA results to both two- and three-dimensional bone microarchitecture from sham and ovariectomized (OVX) rats (n = 10/group). A virtual cylinder of vertebral trabecular bone 40% in length from the caudal side was selected for FEA, because Micro-CT based image analysis indicated the largest differences in microarchitecture between the two groups resided there. Bone stiffness was calculated using FEA and statistically correlated with the three-dimensional values of bone volume/tissue volume, bone mineral density, fractal dimension, trabecular separation, and trabecular bone pattern factor. Our method simplified the process for the assessment of trabecular bone stiffness by FEA from Micro-CT images and highlighted the importance of bone microarchitecture in conferring significantly increased bone quality capable of resisting failure due to increased mechanical loading. PMID:26042089

  14. Using Micro-CT Derived Bone Microarchitecture to Analyze Bone Stiffness – A Case Study on Osteoporosis Rat Bone

    PubMed Central

    Wu, Yuchin; Adeeb, Samer; Doschak, Michael R.

    2015-01-01

    Micro-computed tomography (Micro-CT) images can be used to quantitatively represent bone geometry through a range of computed attenuation-based parameters. Nonetheless, those parameters remain indirect indices of bone microarchitectural strength and require further computational tools to interpret bone structural stiffness and potential for mechanical failure. Finite element analysis (FEA) can be applied to measure trabecular bone stiffness and potentially predict the location of structural failure in preclinical animal models of osteoporosis, although that procedure from image segmentation of Micro-CT derived bone geometry to FEA is often challenging and computationally expensive, resulting in failure of the model to build. Notably, the selection of resolution and threshold for bone segmentation are key steps that greatly affect computational complexity and validity. In the following study, we evaluated an approach whereby Micro-CT derived grayscale attenuation and segmentation data guided the selection of trabecular bone for analysis by FEA. We further correlated those FEA results to both two- and three-dimensional bone microarchitecture from sham and ovariectomized (OVX) rats (n = 10/group). A virtual cylinder of vertebral trabecular bone 40% in length from the caudal side was selected for FEA, because Micro-CT based image analysis indicated the largest differences in microarchitecture between the two groups resided there. Bone stiffness was calculated using FEA and statistically correlated with the three-dimensional values of bone volume/tissue volume, bone mineral density, fractal dimension, trabecular separation, and trabecular bone pattern factor. Our method simplified the process for the assessment of trabecular bone stiffness by FEA from Micro-CT images and highlighted the importance of bone microarchitecture in conferring significantly increased bone quality capable of resisting failure due to increased mechanical loading. PMID:26042089

  15. Serum Dioxin Concentrations and Bone Density and Structure in the Seveso Women’s Health Study

    PubMed Central

    Warner, Marcella; Sirtori, Marcella; Fuerst, Thomas; Rauch, Stephen A.; Brambilla, Paolo; Mocarelli, Paolo; Rubinacci, Alessandro

    2013-01-01

    Background: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a widespread environmental contaminant, is a known endocrine disruptor. In animal studies, TCDD exposure impairs bone metabolism and increases fragility. To our knowledge, no epidemiologic studies have examined this association. Objectives: On 10 July 1976, a chemical explosion in Seveso, Italy, resulted in the highest known residential exposure to TCDD. In 1996, we initiated the Seveso Women’s Health Study, a retrospective cohort study of the health of the women. In 2008, we followed up the cohort. Here, we evaluated the association between TCDD exposure and bone structure and geometry in adulthood, and considered whether timing of TCDD exposure before achievement of peak bone mass (assumed to occur 2 years after onset of menarche) modified the association. Methods: Individual TCDD concentration was measured in archived serum collected soon after the explosion. In 2008, 350 women who were < 20 years old in 1976 underwent a dual-energy X-ray absorptiometry (DXA) bone scan. Bone mineral density was measured at the lumbar spine and hip, and hip geometry was extracted from hip DXA scans using the hip structural analysis method. Results: Among premenopausal women, TCDD serum levels were associated with some indexes indicating better bone structure in women exposed before peak bone mass (n = 219), with stronger associations in those exposed before 5 years of age (n = 46). In contrast, among postmenopausal women, TCDD levels were associated with evidence of better bone structure in women exposed after peak bone mass (n = 48) than in other women (n = 18). Conclusions: Our current results do not support the hypothesis that postnatal TCDD exposure adversely affects adult bone health. Continued follow-up of women who were youngest at exposure is warranted. Future studies should also focus on those exposed in utero. Citation: Eskenazi B, Warner M, Sirtori M, Fuerst T, Rauch SA, Brambilla P, Mocarelli P, Rubinacci A

  16. "Adversative Conjunction": The Poetics of Linguistic Opposition.

    ERIC Educational Resources Information Center

    Wallerstein, Nicholas

    1992-01-01

    The general use of adversative conjunction in (primarily) English and U.S. poetry is outlined. The contention is that the adversative is not merely a grammatical convenience but sometimes a highly functional tool of rhetorical strategy. (36 references) (LB)

  17. Bone Anchored Hearing Aid

    PubMed Central

    2002-01-01

    Executive Summary Objective The objective of this health technology policy assessment was to determine the effectiveness and cost-effectiveness of bone-anchored hearing aid (BAHA) in improving the hearing of people with conduction or mixed hearing loss. The Technology The (BAHA) is a bone conduction hearing device that includes a titanium fixture permanently implanted into the mastoid bone of the skull and an external percutaneous sound processor. The sound processor is attached to the fixture by means of a skin penetrating abutment. Because the device bypasses the middle ear and directly stimulates the cochlea, it has been recommended for individuals with conduction hearing loss or discharging middle ear infection. The titanium implant is expected to last a lifetime while the external sound processor is expected to last 5 years. The total initial device cost is approximately $5,300 and the external sound processor costs approximately $3,500. Review of BAHA by the Medical Advisory Secretariat The Medical Advisory Secretariat’s review is a descriptive synthesis of findings from 36 research articles published between January 1990 and May 2002. Summary of Findings No randomized controlled studies were found. The evidence was derived from level 4 case series with relative small sample sizes (ranging from 30-188). The majority of the studies have follow-up periods of eight years or longer. All except one study were based on monaural BAHA implant on the side with the best bone conduction threshold. Safety Level 4 evidence showed that BAHA has been be implanted safely in adults and children with success rates of 90% or higher in most studies. No mortality or life threatening morbidity has been reported. Revision rates for tissue reduction or resiting were generally under 10% for adults but have been reported to be as high as 25% in pediatric studies. Adverse skin reaction around the skin penetration site was the most common complication reported. Most of these

  18. Bone Marrow Diseases

    MedlinePlus

    Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. ... the platelets that help with blood clotting. With bone marrow disease, there are problems with the stem cells ...

  19. Bone Marrow Transplantation

    MedlinePlus

    Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. ... platelets, which help the blood to clot. A bone marrow transplant is a procedure that replaces a person's ...

  20. Genetics of Bone Density

    MedlinePlus

    ... study linked 32 novel genetic regions to bone mineral density. The findings may help researchers understand why ... or treating osteoporosis. Bones are made of a mineral and protein scaffold filled with bone cells. Bone ...

  1. Calcium and bones

    MedlinePlus

    Bone strength and calcium ... calcium (as well as phosphorus) to make healthy bones. Bones are the main storage site of calcium in ... your body does not absorb enough calcium, your bones can get weak or will not grow properly. ...

  2. Bone biopsy (image)

    MedlinePlus

    A bone biopsy is performed by making a small incision into the skin. A biopsy needle retrieves a sample of bone and it ... examination. The most common reasons for bone lesion biopsy are to distinguish between benign and malignant bone ...

  3. Bone lesion biopsy

    MedlinePlus

    Bone biopsy; Biopsy - bone ... needle is gently pushed and twisted into the bone. Once the sample is obtained, the needle is ... sample is sent to a lab for examination. Bone biopsy may also be done under general anesthesia ...

  4. Bone Quality in Paget's Disease of Bone.

    PubMed

    Singer, Frederick R

    2016-04-01

    Paget's disease of bone is produced by a localized increase in osteoclastic and osteoblastic activity which can progress slowly to involve an entire bone if untreated. A common feature is enlarged bones which are deformed, particularly in weight-bearing regions of the skeleton such as the lower extremity. Pathologic fractures may be a consequence, and nonunion of femoral fractures is not uncommon. Analyses of bone biopsies from patients with Paget's disease indicate that there is a lower, heterogeneous degree of bone mineralization and a younger tissue age than that found in control bone. Pagetic bone also has less resistance to plastic deformation and a straighter crack path than control bone. PMID:26943142

  5. Constant strain rate compression of bovine cortical bone on the Split-Hopkinson Pressure Bar.

    PubMed

    Bekker, A; Cloete, T J; Chinsamy-Turan, A; Nurick, G N; Kok, S

    2015-01-01

    Cortical bone is a visco-elastic material which implies that strain rate will affect its response. Although the Split-Hopkinson Pressure Bar is an accepted technique for determining the dynamic compressive properties of cortical bone it has been shown that the strain rate of compression does not remain constant throughout the duration of a classical experiment with a uniform striker. This raises concerns as to the measurement of smeared responses. This paper presents a shaped striker technique whereby the incident pulse can be shaped to attain a constant strain rate experiment for bovine bone. Shaped strikers offer benefits such as re-usability and increased test repeatability. A comparison of the stress-strain-strain rate responses attained through classical and constant strain rate experiments shows that the shape of the stress-strain curves from conventional experiments is adversely affected in the portion where the strain rate varies. The dynamic response corridors for the two tests are similar, however the ultimate properties are affected. It is concluded that the strain rate history should be presented with dynamic stress-strain responses since the instantaneous strain rate is a likely contributor to potential constitutive models. PMID:25492009

  6. A quantification strategy for missing bone mass in case of osteolytic bone lesions

    SciTech Connect

    Fränzle, Andrea Giske, Kristina; Bretschi, Maren; Bäuerle, Tobias; Hillengass, Jens; Bendl, Rolf

    2013-12-15

    Purpose: Most of the patients who died of breast cancer have developed bone metastases. To understand the pathogenesis of bone metastases and to analyze treatment response of different bone remodeling therapies, preclinical animal models are examined. In breast cancer, bone metastases are often bone destructive. To assess treatment response of bone remodeling therapies, the volumes of these lesions have to be determined during the therapy process. The manual delineation of missing structures, especially if large parts are missing, is very time-consuming and not reproducible. Reproducibility is highly important to have comparable results during the therapy process. Therefore, a computerized approach is needed. Also for the preclinical research, a reproducible measurement of the lesions is essential. Here, the authors present an automated segmentation method for the measurement of missing bone mass in a preclinical rat model with bone metastases in the hind leg bones based on 3D CT scans. Methods: The affected bone structure is compared to a healthy model. Since in this preclinical rat trial the metastasis only occurs on the right hind legs, which is assured by using vessel clips, the authors use the left body side as a healthy model. The left femur is segmented with a statistical shape model which is initialised using the automatically segmented medullary cavity. The left tibia and fibula are segmented using volume growing starting at the tibia medullary cavity and stopping at the femur boundary. Masked images of both segmentations are mirrored along the median plane and transferred manually to the position of the affected bone by rigid registration. Affected bone and healthy model are compared based on their gray values. If the gray value of a voxel indicates bone mass in the healthy model and no bone in the affected bone, this voxel is considered to be osteolytic. Results: The lesion segmentations complete the missing bone structures in a reasonable way. The mean

  7. BONE BANKS

    PubMed Central

    de Alencar, Paulo Gilberto Cimbalista; Vieira, Inácio Facó Ventura

    2015-01-01

    Bone banks are necessary for providing biological material for a series of orthopedic procedures. The growing need for musculoskeletal tissues for transplantation has been due to the development of new surgical techniques, and this has led to a situation in which a variety of hospital services have been willing to have their own source of tissue for transplantation. To increase the safety of transplanted tissues, standards for bone bank operation have been imposed by the government, which has limited the number of authorized institutions. The good performance in a bone bank depends on strict control over all stages, including: formation of well-trained harvesting teams; donor selection; conducting various tests on the tissues obtained; and strict control over the processing techniques used. Combination of these factors enables greater scope of use and numbers of recipient patients, while the incidence of tissue contamination becomes statistically insignificant, and there is traceability between donors and recipients. This paper describes technical considerations relating to how a bone bank functions, the use of grafts and orthopedic applications, the ethical issues and the main obstacles encountered. PMID:27026958

  8. Broken bone

    MedlinePlus

    ... from a height Motor vehicle accidents Direct blow Child abuse Repetitive forces, such as those caused by running, ... you can clearly see a deformity, assume the child has a broken bone and get medical help. Prevention Take the following steps to reduce your risk ...

  9. Fiber optics in adverse environments

    SciTech Connect

    Lyous, P.B.

    1982-01-01

    Radiation effects in optical fibers are considered, taking into account recent progress in the investigation of radiation resistant optical fibers, radiation damage in optical fibers, radiation-induced transient absorption in optical fibers, X-ray-induced transient attenuation at low temperatures in polymer clad silica (PCS) fibers, optical fiber composition and radiation hardness, the response of irradiated optical waveguides at low temperatures, and the effect of ionizing radiation on fiber-optic waveguides. Other topics explored are related to environmental effects on components of fiber optic systems, and radiation detection systems using optical fibers. Fiber optic systems in adverse environments are also discussed, giving attention to the survivability of Army fiber optics systems, space application of fiber optics systems, fiber optic wavelength multiplexing for civil aviation applications, a new fiber optic data bus topology, fiber optics for aircraft engine/inlet control, and application of fiber optics in high voltage substations.

  10. Adverse reactions to food additives.

    PubMed

    Simon, R A

    1986-01-01

    There are thousands of agents that are intentionally added to the food that we consume. These include preservatives, stabilizers, conditioners, thickeners, colorings, flavorings, sweeteners, antioxidants, etc. etc. Yet only a surprisingly small number have been associated with hypersensitivity reactions. Amongst all the additives, FD&C dyes have been most frequently associated with adverse reactions. Tartrazine is the most notorious of them all; however, critical review of the medical literature and current Scripps Clinic studies would indicate that tartrazine has been confirmed to be at best only occasionally associated with flares of urticaria or asthma. There is no convincing evidence in the literature of reactivity to the other azo or nonazo dyes. This can also be said of BHA/BHT, nitrites/nitrates and sorbates. Parabens have been shown to elicit IgE mediated hypersensitivity reactions when used as pharmaceutical preservatives; however, as with the other additives noted above, ingested parabens have only occasionally been associated with adverse reactions. MSG, the cause of the 'Chinese restaurant syndrome' has only been linked to asthma in one report. Sulfiting agents used primarily as food fresheners and to control microbial growth in fermented beverages have been established as the cause of any where from mild to severe and even fatal reactions in at least 5% of the asthmatic population. Other reactions reported to follow sulfite ingestion include anaphylaxis, gastro intestinal complaints and dermatological eruptions. The prevalence of these non asthmatic reactions is unknown. The mechanism of sulfite sensitive asthma is also unknown but most likely involves hyperreactivity to inhale SO2 in the great majority of cases; however, there are reports of IgE mediated reactions and other sulfite sensitive asthmatics have been found with low levels of sulfite oxidase; necessary to oxidize endogenous sulfite to sulfate. PMID:3302664

  11. Correlates of bone quality in older persons

    PubMed Central

    Lauretani, F.; Bandinelli, S.; Russo, C.R.; Maggio, M.; Di Iorio, A.; Cherubini, A.; Maggio, D.; Ceda, G.P.; Valenti, G.; Guralnik, J.M.; Ferrucci, L.

    2009-01-01

    Purpose of the study In a population-based sample of older persons, we studied the relationship between tibial bone density and geometry and factors potentially affecting osteoporosis. Methods Of the 1260 participants aged 65 years or older eligible for the InCHIANTI study, 1155 received an interview and 915 (79.2%) had complete data on tibial QCTscans and other variables used in the analysis presented here. The final study population included 807 persons (372 men and 435 women, age range 65–96 years) after exclusion of participants affected by bone diseases or treated with drugs that interfere with bone metabolism. Results In both sexes, calf cross-sectional muscle area (CSMA) was significantly and independently associated with total bone cross-sectional area (tCSA) and cortical bone cross-sectional area (cCSA) but not with trabecular or cortical volumetric bone mineral density (vBMD). Bioavailable testosterone (Bio-T) was independently associated with both trabecular and cortical vBMD in both sexes. In women, independently of confounders, 25(OH)-vitamin D was positively associated with tCSA and cortical vBMD, while PTH was negatively associated with cortical vBMD. IL-1 beta was negatively correlated with cortical vBMD in women, while TNF-alpha was associated with enhanced bone geometrical adaptation in men. Conclusions Physiological parameters that are generically considered risk factors for osteoporosis were associated with specific bone parameters assessed by tibial QCT. Factors known to be associated with increased bone reabsorption, such as 25(OH)-vitamin D, PTH and Bio-T, affected mainly volumetric BMD, while factors associated with bone mechanical stimulation, such as CSMA, affected primarily bone geometry. Our results also suggested that pro-inflammatory cytokines might be considered as markers of bone resorption. PMID:16709469

  12. Links Between the Microbiome and Bone.

    PubMed

    Hernandez, Christopher J; Guss, Jason D; Luna, Marysol; Goldring, Steven R

    2016-09-01

    The human microbiome has been shown to influence a number of chronic conditions associated with impaired bone mass and bone quality, including obesity, diabetes, and inflammatory bowel disease. The connection between the microbiome and bone health, however, has not been well studied. The few studies available demonstrate that the microbiome can have a large effect on bone remodeling and bone mass. The gut microbiome is the largest reservoir of microbial organisms in the body and consists of more than a thousand different species interacting with one another in a stable, dynamic equilibrium. How the microbiome can affect organs distant from the gut is not well understood but is believed to occur through regulation of nutrition, regulation of the immune system, and/or translocation of bacterial products across the gut endothelial barrier. Here we review each of these mechanisms and discuss their potential effect on bone remodeling and bone mass. We discuss how preclinical studies of bone-microbiome interactions are challenging because the microbiome is sensitive to genetic background, housing environment, and vendor source. Additionally, although the microbiome exhibits a robust response to external stimuli, it rapidly returns to its original steady state after a disturbance, making it difficult to sustain controlled changes in the microbiome over time periods required to detect alterations in bone remodeling, mass, or structure. Despite these challenges, an understanding of the mechanisms by which the gut microbiome affects bone has the potential to provide insights into the dissociation between fracture risk and bone mineral density in patients including those with obesity, diabetes, or inflammatory bowel disease. In addition, alteration of the gut microbiome has the potential to serve as a biomarker of bone metabolic activity as well as a target for therapies to improve bone structure and quality using pharmaceutical agents or pre- or probiotics. © 2016 American

  13. Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing

    PubMed Central

    Fröbel, J.; Prodinger, P. M.; Mrotzek, S. J.; Fischer, J. C.; Zilkens, C.; Bittersohl, B.; Krauspe, R.

    2016-01-01

    Objectives Venous thromboembolism (VTE) is a major potential complication following orthopaedic surgery. Subcutaneously administered enoxaparin has been used as the benchmark to reduce the incidence of VTE. However, concerns have been raised regarding the long-term administration of enoxaparin and its possible negative effects on bone healing and bone density with an increase of the risk of osteoporotic fractures. New oral anticoagulants such as rivaroxaban have recently been introduced, however, there is a lack of information regarding how these drugs affect bone metabolism and post-operative bone healing. Methods We measured the migration and proliferation capacity of mesenchymal stem cells (MSCs) under enoxaparin or rivaroxaban treatment for three consecutive weeks, and evaluated effects on MSC mRNA expression of markers for stress and osteogenic differentiation. Results We demonstrate that enoxaparin, but not rivaroxaban, increases the migration potential of MSCs and increases their cell count in line with elevated mRNA expression of C-X-C chemokine receptor type 4 (CXCR4), tumor necrosis factor alpha (TNFα), and alpha-B-crystallin (CryaB). However, a decrease in early osteogenic markers (insulin-like growth factors 1 and 2 (IGF1, IGF2), bone morphogenetic protein2 (BMP2)) indicated inhibitory effects on MSC differentiation into osteoblasts caused by enoxaparin, but not by rivaroxaban. Conclusions Our findings may explain the adverse effects of enoxaparin treatment on bone healing. Rivaroxaban has no significant impact on MSC metabolism or capacity for osteogenic differentiation in vitro. Cite this article: Dr H. Pilge. Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing. Bone Joint Res 2016;5:95–100. DOI: 10.1302/2046-3758.53.2000595. PMID:26989119

  14. Cancellous bone lamellae strongly affect microcrack propagation and apparent mechanical properties: Separation of patients with osteoporotic fracture from normal controls using a 2D nonlinear finite element method (biomechanical stereology)

    PubMed Central

    Wang, Xiang; Zauel, Roger R.; Rao, D. Sudhaker; Fyhrie, David P.

    2009-01-01

    Biomechanical stereology is proposed as a two-dimensional (2D) finite element (FE) method to estimate the ability of bone tissue to sustain damage and to separate patients with osteoporotic fracture from normal controls. Briefly, 2D nonlinear compact tension FE models were created from quantitative back scattered electron images taken of iliac crest bone specimens collected from the individuals with or without osteoporotic fracture history. The effects of bone mineral microstructure on predicted bone fracture toughness and microcrack propagation were examined. The 2D FE models were used as surrogates for the real bone tissues. The calculated microcrack propagation results and bone mechanical properties were examined as surrogates for measurements from mechanical testing of actual specimens. The results for the 2D FE simulation separated patients with osteoporotic fracture from normal controls even though only the variability in tissue mineral microstructure was used to build the models. The models were deliberately created to ignore all differences in mean mineralization. Hence, the current results support the following hypotheses: (1) that material heterogeneity is important to the separation of patients with osteoporotic fracture from normal controls and; and (2) that 2D nonlinear finite element modeling can produce surrogate mechanical parameters that separate patients with fracture from normal controls. PMID:18378204

  15. Dilatational band formation in bone

    PubMed Central

    Poundarik, Atharva A.; Diab, Tamim; Sroga, Grazyna E.; Ural, Ani; Boskey, Adele L.; Gundberg, Caren M.; Vashishth, Deepak

    2012-01-01

    Toughening in hierarchically structured materials like bone arises from the arrangement of constituent material elements and their interactions. Unlike microcracking, which entails micrometer-level separation, there is no known evidence of fracture at the level of bone’s nanostructure. Here, we show that the initiation of fracture occurs in bone at the nanometer scale by dilatational bands. Through fatigue and indentation tests and laser confocal, scanning electron, and atomic force microscopies on human and bovine bone specimens, we established that dilatational bands of the order of 100 nm form as ellipsoidal voids in between fused mineral aggregates and two adjacent proteins, osteocalcin (OC) and osteopontin (OPN). Laser microdissection and ELISA of bone microdamage support our claim that OC and OPN colocalize with dilatational bands. Fracture tests on bones from OC and/or OPN knockout mice (OC−/−, OPN−/−, OC-OPN−/−;−/−) confirm that these two proteins regulate dilatational band formation and bone matrix toughness. On the basis of these observations, we propose molecular deformation and fracture mechanics models, illustrating the role of OC and OPN in dilatational band formation, and predict that the nanometer scale of tissue organization, associated with dilatational bands, affects fracture at higher scales and determines fracture toughness of bone. PMID:23129653

  16. Adverse events in healthcare: learning from mistakes.

    PubMed

    Rafter, N; Hickey, A; Condell, S; Conroy, R; O'Connor, P; Vaughan, D; Williams, D

    2015-04-01

    Large national reviews of patient charts estimate that approximately 10% of hospital admissions are associated with an adverse event (defined as an injury resulting in prolonged hospitalization, disability or death, caused by healthcare management). Apart from having a significant impact on patient morbidity and mortality, adverse events also result in increased healthcare costs due to longer hospital stays. Furthermore, a substantial proportion of adverse events are preventable. Through identifying the nature and rate of adverse events, initiatives to improve care can be developed. A variety of methods exist to gather adverse event data both retrospectively and prospectively but these do not necessarily capture the same events and there is variability in the definition of an adverse event. For example, hospital incident reporting collects only a very small fraction of the adverse events found in retrospective chart reviews. Until there are systematic methods to identify adverse events, progress in patient safety cannot be reliably measured. This review aims to discuss the need for a safety culture that can learn from adverse events, describe ways to measure adverse events, and comment on why current adverse event monitoring is unable to demonstrate trends in patient safety. PMID:25078411

  17. Changes in bone microstructure and toughness during the healing process of long bones

    NASA Astrophysics Data System (ADS)

    Ishimoto, T.; Nakano, T.; Umakoshi, Y.; Tabata, Y.

    2009-05-01

    It is of great importance to understand how bone defects regain the microstructure and mechanical function of bone and how the microstructure affects the mechanical function during the bone healing process. In the present study on long bone defects, we investigated the relationship between the recovery process of fracture toughness and biological apatite (BAp)/collagen (Col) alignment as an index of the bone microstructure to clarify the bone toughening mechanisms. A 5-mm defect introduced in the rabbit ulna was allowed to heal naturally and a three-point bending test was conducted on the regenerated site to assess bone toughness. The bone toughness was quite low at the early stage of bone regeneration but increased during the postoperative period. The change in toughness agreed well with the characteristics of the fracture surface morphology, which reflected the history of the crack propagation. SEM and microbeam X-ray diffraction analyses indicated that the toughness was dominated by the degree and orientation of the preferred BAp/Col alignment, i.e. bundles aligned perpendicular to the crack propagation clearly contributed to the bone toughening owing to extra energy consumption for resistance to crack propagation. In conclusion, regenerated bone improves fracture toughness by reconstructing the preferred BAp/Col alignment along the bone longitudinal axis during the healing process of long bones.

  18. Life adversity is associated with smoking relapse after a quit attempt.

    PubMed

    Lemieux, Andrine; Olson, Leif; Nakajima, Motohiro; Schulberg, Lauren; al'Absi, Mustafa

    2016-09-01

    Multiple cross-sectional studies have linked adverse childhood events and adult adversities to current smoking, lifetime smoking, and former smoking. To date, however, there have been no direct observational studies assessing the influence of adversities on smoking relapse. We prospectively followed 123 participants, 86 of whom were habitual smokers, from pre-quit ad libitum smoking to four weeks post-quit. Thirty-seven non-smokers were also tested in parallel as a comparison group. Subjects provided biological samples for confirmation of abstinence status and self-report history of adversities such as abuse, neglect, family dysfunction, incarceration, and child-parent separation. They also completed mood and smoking withdrawal symptom measures. The results indicated that within non-smokers and smokers who relapsed within the first month of a quit attempt, but not abstainers, females had significantly higher adversity scores than males. Cigarette craving, which was independent from depressive affect, increased for low adversity participants, but not those with no adversity nor high adversity. These results demonstrate that sex and relapse status interact to predict adversity and that craving for nicotine may be an important additional mediator of relapse. These results add further support to the previous cross-sectional evidence of an adversity and smoking relationship. Further studies to clarify how adversity complicates smoking cessation and impacts smoking behaviors are warranted. PMID:27100471

  19. Inulin, oligofructose and bone health: experimental approaches and mechanisms.

    PubMed

    Weaver, Connie M

    2005-04-01

    Inulin-type fructans have been proposed to benefit mineral retention, thereby enhancing bone health. Many, but not all, experimental animal studies have shown increased mineral absorption by feeding non-digestible oligosaccharides. Possible reasons for inconsistencies are explored. A few studies have reported an enhanced bone mineral density or content. Bone health can be evaluated in chronic feeding studies with bone densitometry, bone breaking strength, bone mineral concentration and bone structure. Isotopic Ca tracers can be used to determine the point of metabolism affected by feeding a functional food ingredient. These methods and the effects of feeding inulin-type fructose are reviewed. Inulin-type fructans enhance Mg retention. Chicory long-chain inulin and oligofructose enhance femoral Ca content, bone mineral density and Ca retention through enhanced Ca absorption and suppressed bone turnover rates, but it is not bone-promoting under all conditions. PMID:15877902

  20. Bone disease in anorexia nervosa.

    PubMed

    Dede, Anastasia D; Lyritis, George P; Tournis, Symeon

    2014-01-01

    Anorexia nervosa is a serious psychiatric disorder accompanied by high morbidity and mortality. It is characterized by emaciation due to self-starvation and displays a unique hormonal profile. Alterations in gonadal axis, growth hormone resistance with low insulin-like growth factor I levels, hypercortisolemia and low triiodothyronine levels are almost universally present and constitute an adaptive response to malnutrition. Bone metabolism is likewise affected resulting in low bone mineral density, reduced bone accrual and increased fracture risk. Skeletal deficits often persist even after recovery from the disease with serious implications for future skeletal health. The pathogenetic mechanisms underlying bone disease are quite complicated and treatment is a particularly challenging task. PMID:24722126

  1. The impact on students of adverse experiences during medical school.

    PubMed

    Wilkinson, Tim J; Gill, Denzil J; Fitzjohn, Julie; Palmer, Claire L; Mulder, Roger T

    2006-03-01

    This study aimed to determine the consequences for, and coping method used by, medical students who experienced adverse experiences during their training. A nationwide questionnaire based census of all current medical students in New Zealand. The response rate was 83% (1384/1660). Two-thirds of students had at least one adverse experience, with humiliation being the most common and having the greatest adverse impact. Unwanted sexual advances, unfair treatment on the basis of gender or race had a lesser impact for most students. Most students took several hours or several days to get over an adverse episode and most commonly they then avoided that person or department. Around one half sought help. Only one-quarter felt it motivated their learning while one-sixth felt it made them consider leaving medical school. The most common perpetrators were senior doctors or nurses. Unwanted sexual advances were most common from other students or from patients. Humiliation is the experience that affected students the most and had a significant adverse effect on learning. There is a disturbing rate of unacceptable practice within medical schools, not all of which is from doctors. PMID:16707293

  2. Drilling of bone: A comprehensive review

    PubMed Central

    Pandey, Rupesh Kumar; Panda, S.S.

    2013-01-01

    Background Bone fracture treatment usually involves restoring of the fractured parts to their initial position and immobilizing them until the healing takes place. Drilling of bone is common to produce hole for screw insertion to fix the fractured parts for immobilization. Orthopaedic drilling during surgical process causes increase in the bone temperature and forces which can cause osteonecrosis reducing the stability and strength of the fixation. Methods A comprehensive review of all the relevant investigations carried on bone drilling is conducted. The experimental method used, results obtained and the conclusions made by the various researchers are described and compared. Result Review suggests that the further improvement in the area of bone drilling is possible. The systematic review identified several consequential factors (drilling parameters and drill specifications) affecting bone drilling on which there no general agreement among investigators or are not adequately evaluated. These factors are highlighted and use of more advanced methods of drilling is accentuated. The use of more precise experimental set up which resembles the actual situation and the development of automated bone drilling system to minimize human error is addressed. Conclusion In this review, an attempt has been made to systematically organize the research investigations conducted on bone drilling. Methods of treatment of bone fracture, studies on the determination of the threshold for thermal osteonecrosis, studies on the parameters influencing bone drilling and methods of the temperature measurement used are reviewed and the future work for the further improvement of bone drilling process is highlighted. PMID:26403771

  3. Inherited Bone Marrow Failure Syndromes (IBMFS)

    Cancer.gov

    The NCI IBMFS Cohort Study consists of affected individuals and their immediate families in North America who have an inherited bone marrow failure syndrome (IBMFS)-either one that has been specifically identified and defined, or bone marrow failure that appears to be inherited but has not yet been clearly identified as having a genetic basis.

  4. Thyroid-Disrupting Chemicals: Interpreting Upstream Biomarkers of Adverse Outcomes

    PubMed Central

    Miller, Mark D.; Crofton, Kevin M.; Rice, Deborah C.; Zoeller, R. Thomas

    2009-01-01

    Background There is increasing evidence in humans and in experimental animals for a relationship between exposure to specific environmental chemicals and perturbations in levels of critically important thyroid hormones (THs). Identification and proper interpretation of these relationships are required for accurate assessment of risk to public health. Objectives We review the role of TH in nervous system development and specific outcomes in adults, the impact of xenobiotics on thyroid signaling, the relationship between adverse outcomes of thyroid disruption and upstream causal biomarkers, and the societal implications of perturbations in thyroid signaling by xenobiotic chemicals. Data sources We drew on an extensive body of epidemiologic, toxicologic, and mechanistic studies. Data synthesis THs are critical for normal nervous system development, and decreased maternal TH levels are associated with adverse neuropsychological development in children. In adult humans, increased thyroid-stimulating hormone is associated with increased blood pressure and poorer blood lipid profiles, both risk factors for cardiovascular disease and death. These effects of thyroid suppression are observed even within the “normal” range for the population. Environmental chemicals may affect thyroid homeostasis by a number of mechanisms, and multiple chemicals have been identified that interfere with thyroid function by each of the identified mechanisms. Conclusions Individuals are potentially vulnerable to adverse effects as a consequence of exposure to thyroid-disrupting chemicals. Any degree of thyroid disruption that affects TH levels on a population basis should be considered a biomarker of adverse outcomes, which may have important societal outcomes. PMID:19654909

  5. Numerical analysis of an osseointegrated prosthesis fixation with reduced bone failure risk and periprosthetic bone loss.

    PubMed

    Tomaszewski, P K; van Diest, M; Bulstra, S K; Verdonschot, N; Verkerke, G J

    2012-07-26

    Currently available implants for direct attachment of prosthesis to the skeletal system after transfemoral amputation (OPRA system, Integrum AB, Sweden and ISP Endo/Exo prosthesis, ESKA Implants AG, Germany) show many advantages over the conventional socket fixation. However, restraining biomechanical issues such as considerable bone loss around the stem and peri-prosthetic bone fractures are present. To overcome these limiting issues a new concept of the direct intramedullary fixation was developed. We hypothesize that the new design will reduce the peri-prosthetic bone failure risk and adverse bone remodeling by restoring the natural load transfer in the femur. Generic CT-based finite element models of an intact femur and amputated bones implanted with 3 analyzed implants were created and loaded with a normal walking and a forward fall load. The strain adaptive bone remodeling theory was used to predict long-term bone changes around the implants and the periprosthetic bone failure risk was evaluated by the von Mises stress criterion. The results show that the new design provides close to physiological distribution of stresses in the bone and lower bone failure risk for the normal walking as compared to the OPRA and the ISP implants. The bone remodeling simulations did not reveal any overall bone loss around the new design, as opposed to the OPRA and the ISP implants, which induce considerable bone loss in the distal end of the femur. This positive outcome shows that the presented concept has a potential to considerably improve safety of the rehabilitation with the direct fixation implants. PMID:22677337

  6. In vivo microdamage is an indicator of susceptibility to initiation and propagation of microdamage in human femoral trabecular bone.

    PubMed

    Wu, Ziheng; Laneve, Anthony J; Niebur, Glen L

    2013-07-01

    Microdamage has been cited as an important element of trabecular bone quality and fracture risk, as materials with flaws have lower modulus and strength than equivalent undamaged materials. However, the magnitude of the effect of damage on failure properties depends on its tendency to propagate. Human femoral trabecular bone from the neck and greater trochanter was subjected to one of compressive, torsional, or combined compression and torsion. The in vivo, new, and propagating damage were then quantified in thick sections under epifluorescent microscopy. Multiaxial loading, which was intended to represent an off-axis load such as a fall or accident, caused much more damage than either simple compression or shear, and similarly caused the greatest stiffness loss. In all cases, initiation of new damage far exceeded the propagation of existing damage. This may reflect stress redistribution away from damaged trabeculae, resulting in new damage sites. However, the accumulation of new damage was positively correlated with quantity of pre-existing damage in all loading modes, indicating that damaged bone is inherently more prone to further damage formation. Moreover, about 50% of in vivo microcracks propagated under each type of loading. Finally, damage formation was positively correlated to decreased compressive stiffness following both axial and shear loading. Taken together, these results demonstrate that damage in trabecular bone adversely affects its mechanical properties, and is indicative of bone that is more susceptible to further damage. PMID:23459314

  7. Exercise hypertension: an adverse prognosis?

    PubMed

    Smith, Ryan G; Rubin, Stanley A; Ellestad, Myrvin H

    2009-01-01

    We sought to clarify the prognostic importance of an "exaggerated" or "hypertensive" systolic blood pressure response to exercise during an exercise test. Studies evaluating the prognosis for cardiovascular events and cardiovascular mortality in those with hypertension during exercise testing were systematically reviewed. Fourteen studies were identified. Six studies were of healthy volunteers or hypertensives. Eight studies were in subjects with known or suspected heart disease. Without established heart disease, exercise hypertension predicted cardiovascular events and cardiovascular death. However, two of the six studies included a multivariate analysis; both demonstrated no independent association. Studies in subjects with known or suspected heart disease demonstrated that exercise hypertension predicted fewer cardiac events and lesser mortality or, after multivariate adjustment, no associated risk. In a healthy population, a higher exercise blood pressure may indicate hypertension or prehypertension, instead of normal vascular function, and an associated long-term adverse prognosis. In a population with a high burden of heart disease, the highest risk subjects with the most extensive cardiac disease may not be capable of generating pressure or workload to allow the manifestation of exercise systolic hypertension. By comparison, therefore, those with exercise hypertension have a better prognosis. PMID:20409979

  8. OAE: The Ontology of Adverse Events

    PubMed Central

    2014-01-01

    Background A medical intervention is a medical procedure or application intended to relieve or prevent illness or injury. Examples of medical interventions include vaccination and drug administration. After a medical intervention, adverse events (AEs) may occur which lie outside the intended consequences of the intervention. The representation and analysis of AEs are critical to the improvement of public health. Description The Ontology of Adverse Events (OAE), previously named Adverse Event Ontology (AEO), is a community-driven ontology developed to standardize and integrate data relating to AEs arising subsequent to medical interventions, as well as to support computer-assisted reasoning. OAE has over 3,000 terms with unique identifiers, including terms imported from existing ontologies and more than 1,800 OAE-specific terms. In OAE, the term ‘adverse event’ denotes a pathological bodily process in a patient that occurs after a medical intervention. Causal adverse events are defined by OAE as those events that are causal consequences of a medical intervention. OAE represents various adverse events based on patient anatomic regions and clinical outcomes, including symptoms, signs, and abnormal processes. OAE has been used in the analysis of several different sorts of vaccine and drug adverse event data. For example, using the data extracted from the Vaccine Adverse Event Reporting System (VAERS), OAE was used to analyse vaccine adverse events associated with the administrations of different types of influenza vaccines. OAE has also been used to represent and classify the vaccine adverse events cited in package inserts of FDA-licensed human vaccines in the USA. Conclusion OAE is a biomedical ontology that logically defines and classifies various adverse events occurring after medical interventions. OAE has successfully been applied in several adverse event studies. The OAE ontological framework provides a platform for systematic representation and analysis of

  9. Bone banking and sterilization of bones

    NASA Astrophysics Data System (ADS)

    Minamisawa, I.; Itoman, M.; Maehara, H.; Kobayashi, A.; Watanabe, T.

    1995-08-01

    The use of banked bone (preserved allograft bone) is various and essential, because it has numerous advantages including the relative ease in retrieval a large amount of bone material and requisite shape and size. But bone banking and allografting must be promoted under obligation to stably supply safe and high-quality bone. To avoid transferring disease perfectly, irradiation sterilization is especially recommended at the present time.

  10. Changing Medicine and Building Community: Maine’s Adverse Childhood Experiences Momentum

    PubMed Central

    Forstadt, Leslie; Cooper, Sally; Andrews, Sue Mackey

    2015-01-01

    Physicians are instrumental in community education, prevention, and intervention for adverse childhood experiences. In Maine, a statewide effort is focusing on education about adverse childhood experiences and ways that communities and physicians can approach childhood adversity. This article describes how education about adversity and resilience can positively change the practice of medicine and related fields. The Maine Resilience Building Network brings together ongoing programs, supports new ventures, and builds on existing resources to increase its impact. It exemplifies the collective impact model by increasing community knowledge, affecting medical practice, and improving lives. PMID:25902346

  11. Association of chemerin levels and bone mineral density in Chinese obese postmenopausal women.

    PubMed

    Shi, Liang; Mao, Chaoming; Wang, Xuefeng; Liu, Rencong; Li, Lin; Mou, Xiao; Xu, Ping; Li, Hongli; Xu, Chengcheng; Yuan, Guoyue; Wang, Bin; Zhang, Hao

    2016-08-01

    Increasing evidence suggests the association between obesity and bone metabolism. However, whether excessive fat accumulation has a beneficial or adverse effect on bone health remains controversial. Chemerin is a novel adipocyte-derived hormone and a chemoattractant cytokine that regulates adipogenesis. This study was performed to investigate the associations of serum chemerin with bone mineral density (BMD) and serum pro-inflammatory cytokine levels in 543 Chinese obese postmenopausal women. BMD of the femoral neck and lumbar spine, lean mass, and fat mass were measured using dual energy X-ray absorptiometry. Anthropometric assessment and laboratory measurements were performed. The age, time after menopause, and fat mass were negatively correlated with femoral and lumbar BMD, whereas lean mass was positively correlated with aforementioned variables. Furthermore, BMD at the lumbar spine was inversely associated with serum chemerin and TNF-α levels (r = -0.155, P = 0.001; r = -0.147, P = 0.001). Multiple linear regression analyses showed that serum chemerin levels were negatively correlated with BMD at the lumbar site after controlling for the age, lean, and fat mass (β = -0.125, P = 0.001). Chronic low-grade inflammation state in obese population has an inverse effect on bone mass. Chemerin as an adipocytokine and chemoattractant negatively affects the bone mass of Chinese obese postmenopausal women. Further studies are needed to confirm the potential role of chemerin in the crosstalk between bone and fat accumulation in obese population. PMID:27583869

  12. Association of chemerin levels and bone mineral density in Chinese obese postmenopausal women

    PubMed Central

    Shi, Liang; Mao, Chaoming; Wang, Xuefeng; Liu, Rencong; Li, Lin; Mou, Xiao; Xu, Ping; Li, Hongli; Xu, Chengcheng; Yuan, Guoyue; Wang, Bin; Zhang, Hao

    2016-01-01

    Abstract Increasing evidence suggests the association between obesity and bone metabolism. However, whether excessive fat accumulation has a beneficial or adverse effect on bone health remains controversial. Chemerin is a novel adipocyte-derived hormone and a chemoattractant cytokine that regulates adipogenesis. This study was performed to investigate the associations of serum chemerin with bone mineral density (BMD) and serum pro-inflammatory cytokine levels in 543 Chinese obese postmenopausal women. BMD of the femoral neck and lumbar spine, lean mass, and fat mass were measured using dual energy X-ray absorptiometry. Anthropometric assessment and laboratory measurements were performed. The age, time after menopause, and fat mass were negatively correlated with femoral and lumbar BMD, whereas lean mass was positively correlated with aforementioned variables. Furthermore, BMD at the lumbar spine was inversely associated with serum chemerin and TNF-α levels (r = −0.155, P = 0.001; r = −0.147, P = 0.001). Multiple linear regression analyses showed that serum chemerin levels were negatively correlated with BMD at the lumbar site after controlling for the age, lean, and fat mass (β = −0.125, P = 0.001). Chronic low-grade inflammation state in obese population has an inverse effect on bone mass. Chemerin as an adipocytokine and chemoattractant negatively affects the bone mass of Chinese obese postmenopausal women. Further studies are needed to confirm the potential role of chemerin in the crosstalk between bone and fat accumulation in obese population. PMID:27583869

  13. A long term histological analysis of effect of interposed hydroxyapatite between bone and bone cement in THA and TKA.

    PubMed

    Oonishi, Hironobu

    2012-01-01

    The standard cementing technique for total hip and knee arthroplasty (THA, TKA) was modified by interposing osteoconductive porous polycrystalline hydroxyapatite (HA) granules at the cement-bone interface to augment cement-bone bonding. Twenty-one specimens from the acetabulum and two specimens from the femur containing well-fixed bone-cement interface were retrieved five months to twenty-two years after THA and TKA with an interface bioactive bone cement technique. Histological findings were evaluated in terms of the retrieved sites, the interval between index operation and revision, patient age at retrieval and bone pathology. Dense bone ingrowth was observed in all specimens retrieved from the superior wall of the acetabulum. Cancellous bone ingrowth was observed in specimens retrieved from the infero-medial wall of the acetabulum. Connective tissue interposition and osteolysis were observed at the sites where hydroxyapatite granules were absent. Findings of bone ingrowth for the HA interposed retrievals were similar regardless of the interval between index operation and revision, patient age at retrieval, and bone pathology. Longer survivability of the bone-cement bonding was attributed more to the interposed HA granules. In spite of various degrees of aging, postmenopausal osteoporosis, and pathological bone condition the histological findings were not affected by the bone pathology. There was long-term direct contact between the bone and hydroxyapatite granules. Thus, the interface bioactive bone cement technique can ensure longevity of bone-cement bonding even after the onset of osteoporosis and for pathological bone conditions. PMID:23428252

  14. Effects of Exercise on Bone Mineral Content in Postmenopausal Women.

    ERIC Educational Resources Information Center

    Rikli, Roberta E.; McManis, Beth G.

    1990-01-01

    Study tested the effect of exercise programs on bone mineral content (BMC) and BMC/bone width in 31 postmenopausal women. Subjects were placed in groups with aerobic exercise, aerobics plus upper-body weight training, or no exercise. Results indicate that regular exercise programs positively affect bone mineral maintenance in postmenopausal women.…

  15. Severe cutaneous adverse drug reactions.

    PubMed

    Chung, Wen-Hung; Wang, Chuang-Wei; Dao, Ro-Lan

    2016-07-01

    The clinical manifestations of drug eruptions can range from mild maculopapular exanthema to severe cutaneous adverse drug reactions (SCAR), including drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) which are rare but occasionally fatal. Some pathogens may induce skin reactions mimicking SCAR. There are several models to explain the interaction of human leukocyte antigen (HLA), drug and T-cell receptor (TCR): (i) the "hapten/prohapten" theory; (ii) the "p-i concept"; (iii) the "altered peptide repertoire"; and (iv) the "altered TCR repertoire". The checkpoints of molecular mechanisms of SCAR include specific drug antigens interacting with the specific HLA loci (e.g. HLA-B*15:02 for carbamazepine-induced SJS/TEN and HLA-B*58:01 for allopurinol-induced SCAR), involvement of specific TCR, induction of T-cell-mediated responses (e.g. granulysin, Fas ligand, perforin/granzyme B and T-helper 1/2-associated cytokines) and cell death mechanism (e.g. miR-18a-5p-induced apoptosis; annexin A1 and formyl peptide receptor 1-induced necroptosis in keratinocytes). In addition to immune mechanism, metabolism has been found to play a role in the pathogenesis of SCAR, such as recent findings of strong association of CYP2C9*3 with phenytoin-induced SCAR and impaired renal function with allopurinol SCAR. With a better understanding of the mechanisms, effective therapeutics and prevention for SCAR can be improved. PMID:27154258

  16. Effects of Timing of Adversity on Adolescent and Young Adult Adjustment

    PubMed Central

    Kiff, Cara J.; Cortes, Rebecca; Lengua, Lilana; Kosterman, Rick; Hawkins, J. David; Mason, W. Alex

    2012-01-01

    Effects of Timing of Adversity on Adolescent and Young Adult Adjustment Abstract Exposure to adversity during childhood and adolescence predicts adjustment across development. Further, adolescent adjustment problems persist into young adulthood. This study examined relations of contextual adversity with concurrent adolescent adjustment and prospective mental health and health outcomes in young adulthood. A longitudinal sample (N = 808) was followed from age 10 through 27. Perceptions of neighborhood in childhood predicted depression, alcohol use disorders, and HIV risk in young adulthood. Further, the timing of adversity was important in determining the type of problem experienced in adulthood. Youth adjustment predicted adult outcomes, and in some cases, mediated the relation between adversity and outcomes. These findings support the importance of adversity in predicting adjustment and elucidate factors that affect outcomes into young adulthood. PMID:22754271

  17. Effects of Timing of Adversity on Adolescent and Young Adult Adjustment.

    PubMed

    Kiff, Cara J; Cortes, Rebecca; Lengua, Lilana; Kosterman, Rick; Hawkins, J David; Mason, W Alex

    2012-06-01

    Effects of Timing of Adversity on Adolescent and Young Adult Adjustment Abstract Exposure to adversity during childhood and adolescence predicts adjustment across development. Further, adolescent adjustment problems persist into young adulthood. This study examined relations of contextual adversity with concurrent adolescent adjustment and prospective mental health and health outcomes in young adulthood. A longitudinal sample (N = 808) was followed from age 10 through 27. Perceptions of neighborhood in childhood predicted depression, alcohol use disorders, and HIV risk in young adulthood. Further, the timing of adversity was important in determining the type of problem experienced in adulthood. Youth adjustment predicted adult outcomes, and in some cases, mediated the relation between adversity and outcomes. These findings support the importance of adversity in predicting adjustment and elucidate factors that affect outcomes into young adulthood. PMID:22754271

  18. Lead-induced adverse effects on the reproductive system of rats with particular reference to histopathological changes in uterus

    PubMed Central

    Nakade, Udayraj Premdas; Garg, Satish Kumar; Sharma, Abhishek; Choudhury, Soumen; Yadav, Rajkumar Singh; Gupta, Kuldeep; Sood, Naresh

    2015-01-01

    Objectives: This study was undertaken to elucidate the adverse effect of lead on female reproductive system following in vivo exposure in rats. Materials and Methods: Animals of Group II, III and IV received lead acetate in drinking water (30, 100 and 300 ppm, respectively) for 28 days whereas Group I served as control. Lead levels in digested blood and bone samples were measured using atomic absorption spectrophotometer. 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. PMID:25821306

  19. Biofabrication of bone tissue: approaches, challenges and translation for bone regeneration.

    PubMed

    Tang, Daniel; Tare, Rahul S; Yang, Liang-Yo; Williams, David F; Ou, Keng-Liang; Oreffo, Richard O C

    2016-03-01

    The rising incidence of bone disorders has resulted in the need for more effective therapies to meet this demand, exacerbated by an increasing ageing population. Bone tissue engineering is seen as a means of developing alternatives to conventional bone grafts for repairing or reconstructing bone defects by combining biomaterials, cells and signalling factors. However, skeletal tissue engineering has not yet achieved full translation into clinical practice as a consequence of several challenges. The use of additive manufacturing techniques for bone biofabrication is seen as a potential solution, with its inherent capability for reproducibility, accuracy and customisation of scaffolds as well as cell and signalling factor delivery. This review highlights the current research in bone biofabrication, the necessary factors for successful bone biofabrication, in addition to the current limitations affecting biofabrication, some of which are a consequence of the limitations of the additive manufacturing technology itself. PMID:26803405

  20. Bone scan appearances following bone and bone marrow biopsy

    SciTech Connect

    McKillop, J.H.; Maharaj, D.; Boyce, B.F.; Fogelman, I.

    1984-01-01

    Bone marrow and bone biopsies are performed not infrequently in patients referred for bone scans and represent a potential cause of a ''false positive'' focal abnormality on the bone scan. The authors have therefore examined the scan appearances in a series of patients who had undergone either sternal marrow biopsy, (Salah needle, diameter 1.2 mm) trephine iliac crest marrow biopsy (Jamshidi 11 gauge needle, diameter 3.5 mm) or a transiliac bone biopsy (needle diameter 8 mm). Of 18 patients studied 1 to 45 days after sternal marrow 17 had normal scan appearances at the biopsy site and 1 had a possible abnormality. None of 9 patients studied 4 to 19 days after trephine iliac crest marrow biopsy had a hot spot at the biopsy site. A focal scan abnormality was present at the biopsy site in 9/11 patients studied 5 to 59 days after a trans iliac bone biopsy. No resultant scan abnormality was seen in 4 patients imaged within 3 days of the bone biopsy or in 3 patients imaged 79 to 138 days after the procedure. Bone marrow biopsy of the sternum or iliac crest does not usually cause bone scan abnormalities. A focal abnormality at the biopsy site is common in patients imaged 5 days to 2 months after bone biopsy. The gauge of the needle employed in the biopsy and thus the degree of bone trauma inflicted, is likely to be main factor determining the appearance of bone scan abnormalities at the biopsy site.

  1. Bone age in cerebral palsy

    PubMed Central

    Miranda, Eduardo Régis de Alencar Bona; Palmieri, Maurício D'arc; de Assumpção, Rodrigo Montezuma César; Yamada, Helder Henzo; Rancan, Daniela Regina; Fucs, Patrícia Maria de Moraes Barros

    2013-01-01

    Objective To compare the chronological age and bone age among cerebral palsy patients in the outpatient clinic and its correlation with the type of neurological involvement, gender and functional status. Methods 401 patients with spastic cerebral palsy, and ages ranging from three months to 20 years old, submitted to radiological examination for bone age and analyzed by two independent observers according Greulich & Pyle. Results In the topographic distribution, there was a significant delay (p<0.005) in tetraparetic (17.7 months), hemiparetic (10.1 months), and diparetic patients (7.9 months). In the hemiparetic group, the mean bone age in the affected side was 96.88 months and the uncompromised side was 101.13 months (p<0.005). Regarding functional status, the ambulatory group showed a delay of 18.73 months in bone age (p<0.005). Comparing bone age between genders, it was observed a greater delay in males (13.59 months) than in females (9.63 months), but not statistically significant (p = 0.54). Conclusion There is a delay in bone age compared to chronological age influenced by the topography of spasticity, functional level and gender in patients with cerebral palsy. Level of Evidence IV, Case Series. PMID:24453693

  2. Physiological effects of microgravity on bone cells.

    PubMed

    Arfat, Yasir; Xiao, Wei-Zhong; Iftikhar, Salman; Zhao, Fan; Li, Di-Jie; Sun, Yu-Long; Zhang, Ge; Shang, Peng; Qian, Ai-Rong

    2014-06-01

    Life on Earth developed under the influence of normal gravity (1g). With evidence from previous studies, scientists have suggested that normal physiological processes, such as the functional integrity of muscles and bone mass, can be affected by microgravity during spaceflight. During the life span, bone not only develops as a structure designed specifically for mechanical tasks but also adapts for efficiency. The lack of weight-bearing forces makes microgravity an ideal physical stimulus to evaluate bone cell responses. One of the most serious problems induced by long-term weightlessness is bone mineral loss. Results from in vitro studies that entailed the use of bone cells in spaceflights showed modification in cell attachment structures and cytoskeletal reorganization, which may be involved in bone loss. Humans exposed to microgravity conditions experience various physiological changes, including loss of bone mass, muscle deterioration, and immunodeficiency. In vitro models can be used to extract valuable information about changes in mechanical stress to ultimately identify the different pathways of mechanotransduction in bone cells. Despite many in vivo and in vitro studies under both real microgravity and simulated conditions, the mechanism of bone loss is still not well defined. The objective of this review is to summarize the recent research on bone cells under microgravity conditions based on advances in the field. PMID:24687524

  3. [Acute adverse effects of dialysis].

    PubMed

    Opatrný, K

    2003-02-01

    Adverse reactions to dialyzers are a not very frequent, but because of the serious, sometimes fatal course, a dreaded complication of haemodialysis treatment. Most important among these reactions are hypersensitive reactions (anaphylactoid, reaction type A to dialyzer), which develop as a rule within the 10th minute of the procedure, and the reaction caused by the action of perfluorohydrocarbon which develop hours after onset or even completion of haemodialysis. Explanation of the development of hypersensitive reactions (HSR) by complement activation and formation of anaphylatoxins C3a and C5a during contact of blood with the bioincompatible dialysis membrane has been abandoned. Evidence of the etiological role of ethylene oxide (ETO) in the development of HSR influenced the selection of materials for the production of dialyzers and sterilization during manufacture, it emphasized the importance of rinsing of the dialyzer in the dialysis centre and led to the wide application of alternative methods of sterilization by gamma radiation and steam. HSR may be also caused by overproduction of bradykinin and inhibition of its degradation or degradation of its metabolites. Excessive bradykinin production caused by dialysis membranes with a negative charge is potentiated e.g. by a lower pH and increased plasma dilution in the initial stage of haemodialysis. Inhibition of bradykinin degradation develops during treatment with angiotensin converting enzyme inhibitors (ACEI). In prevention of HSR associated with bradykinin in addition to elimination of a combination of a negatively charged dialysis membrane and ACEI treatment a part is played also by rinsing of the dialyzer before haemodialysis with a bicarbonate solution and the modification of the membrane surface (implemented by the manufacturer) which reduces its negative charge. The first reaction to the dialyzer in conjunction with perfluorohydrocarbon (PF-5070), used in production of some dialyzers for testing the

  4. Chitosan and alginate scaffolds for bone tissue regeneration.

    PubMed

    Olmez, S S; Korkusuz, P; Bilgili, H; Senel, S

    2007-06-01

    Polymeric scaffold for tissue regeneration was developed for veterinary applications. Oxytetracycline hydrochloride (OTC), which is a widely used antibiotic in veterinary medicine was chosen as the model compound. Gel formulations using chitosan and alginate were prepared in distilled water or in 1% (v/v) acetic acid solution. Sponges were also prepared by a freeze-drying process. Tripolyphosphate was used for cross-linking. Viscosity was decreased in the presence of OTC in chitosan gels whereas no difference was found with alginate gels. All gels showed pseudoplastic behaviour. Water absorption capacity was highest with chitosan/alginate sponges. The solvent used for preparation of the chitosan gels was found to affect the release of OTC. The release of OTC from the sponges was increased by cross-linking. Chitosan/alginate sponges showed the slowest and lowest drug release among the developed sponge formulations in this study. The formulations were found to be biocompatible, inducing no adverse reaction in vivo on surgically formed bone defects of radius of rabbits. The level of organization of the remodelled new bone in the treatment groups was better than that of control. Incorporation of OTC into formulations did not show any considerable enhancing effect. PMID:17663189

  5. A diet high in meat protein and potential renal acid load increases fractional Ca absorption and urinary Ca excretion, without affecting markers of bone resorption or formation in postmenopausal women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: The objective was to determine the effects of high dietary protein (mostly meat) and high potential renal acid load (PRAL) on calcium (Ca) balance and markers of bone metabolism. Methods: In a randomized crossover design, sixteen healthy postmenopausal women consumed two diets: one with l...

  6. Imaging findings of various talus bone tumors-clinico-radiologic features of talus bone tumors.

    PubMed

    Jeon, Ji Young; Chung, Hye Won; Kwon, Jong Won; Hong, Sung Hwan; Lee, Guen Young; Ryu, Kyung Nam

    2016-01-01

    Osseous neoplasms of the foot are uncommon, accounting for only 3.3% of all primary bone tumors. Bone tumors of the talus are even rarer, and there are not many publications that comprehensively evaluate the imaging findings of talus tumors. The purpose of this article is to review the benign and malignant bone tumors affecting this uncommon site and to describe the clinical and radiologic features of each tumor. PMID:27317211

  7. Cytokines and growth factors which regulate bone cell function

    NASA Astrophysics Data System (ADS)

    Seino, Yoshiki

    Everybody knows that growth factors are most important in making bone. Hormones enhance bone formation from a long distance. Growth factors promote bone formation as an autocrine or paracrine factor in nearby bone. BMP-2 through BMP-8 are in the TGF-β family. BMP makes bone by enchondral ossification. In bone, IGF-II is most abundant, second, TGF-β, and third IGF-I. TGF-β enhances bone formation mainly by intramembranous ossification in vivo. TGF-β affects both cell proliferation and differentiation, however, TGF-β mainly enhances bone formation by intramembranous ossification. Interestingly, TGF-β is increased by estrogen(E 2), androgen, vitamin D, TGF-β and FGF. IGF-I and IGF-II also enhance bone formation. At present it remains unclear why IGF-I is more active in bone formation than IGF-II, although IGF-II is more abundant in bone compared to IGF-I. However, if only type I receptor signal transduction promotes bone formation, the strong activity of IGF-I in bone formation is understandable. GH, PTH and E 2 promotes IGF-I production. Recent data suggest that hormones containing vitamin D or E 2 enhance bone formation through growth factors. Therefore, growth factors are the key to clarifying the mechanism of bone formation.

  8. The effects of bone density and crestal cortical bone thickness on micromotion and peri-implant bone strain distribution in an immediately loaded implant: a nonlinear finite element analysis

    PubMed Central

    2016-01-01

    Purpose This study investigated the effects of bone density and crestal cortical bone thickness at the implant-placement site on micromotion (relative displacement between the implant and bone) and the peri-implant bone strain distribution under immediate-loading conditions. Methods A three-dimensional finite element model of the posterior mandible with an implant was constructed. Various bone parameters were simulated, including low or high cancellous bone density, low or high crestal cortical bone density, and crestal cortical bone thicknesses ranging from 0.5 to 2.5 mm. Delayed- and immediate-loading conditions were simulated. A buccolingual oblique load of 200 N was applied to the top of the abutment. Results The maximum extent of micromotion was approximately 100 μm in the low-density cancellous bone models, whereas it was under 30 μm in the high-density cancellous bone models. Crestal cortical bone thickness significantly affected the maximum micromotion in the low-density cancellous bone models. The minimum principal strain in the peri-implant cortical bone was affected by the density of the crestal cortical bone and cancellous bone to the same degree for both delayed and immediate loading. In the low-density cancellous bone models under immediate loading, the minimum principal strain in the peri-implant cortical bone decreased with an increase in crestal cortical bone thickness. Conclusions Cancellous bone density may be a critical factor for avoiding excessive micromotion in immediately loaded implants. Crestal cortical bone thickness significantly affected the maximum extent of micromotion and peri-implant bone strain in simulations of low-density cancellous bone under immediate loading. PMID:27382504

  9. The Effects of RANKL Inhibition on Fracture Healing and Bone Strength in a Mouse Model of Osteogenesis Imperfecta

    PubMed Central

    Delos, D.; Yang, X.; Ricciardi, B.F.; Myers, E.R.; Bostrom, M.P.G.; Pleshko Camacho, N.

    2009-01-01

    Summary Currently, the standard treatment for osteogenesis imperfecta (OI) is bisphosphonate therapy. Recent studies, however, have shown delayed healing of osteotomies in a subset of OI patients treated with such agents. The current study sought to determine the effects of another therapy, RANKL inhibition, on bone healing and bone strength in the growing oim/oim mouse, a model of moderate-to-severe OI. Mice (73 oim/oim and 69 wildtype (WT)) were injected twice weekly with either soluble murine RANK (RANK-Fc) (1.5mg/kg) or saline beginning at 6 weeks of age. At 8 weeks of age, the animals underwent transverse mid-diaphyseal osteotomies of the right femur. Therapy was continued until sacrifice at 2, 3, 4 or 6 weeks post-fracture. At 6 weeks post-fracture, greater callus area (6.59±3.78mm2 vs 2.67±2.05mm2, p=0.003) and increased radiographic intensity (mineral density) (0.48 ± 0.14 vs. 0.30 ± 0.80, p=0.005) were found in the RANK-Fc vs saline oim/oim group, indicating a delay in callus remodeling. Despite this delay, mechanical tests at 6 weeks post-fracture revealed no significant differences in whole bone properties of stiffness and failure moment. Further, RANKL inhibition resulted in a greater failure moment and greater work to failure for the non-fractured contralateral WT bones compared to the non-fractured saline WT bones. Together, these results demonstrate that RANKL-inhibition does not adversely affect the mechanical properties of healing bone in the oim/oim mice, and is associated with increased strength in intact bone in the WT mice. PMID:17729310

  10. Facts about Broken Bones

    MedlinePlus

    ... las fracturas de huesos Your bones are tough stuff — but even tough stuff can break. Like a wooden pencil, bones will ... that? Get a lot of physical activity, especially stuff like jumping and running. Feed your bones the ...

  11. Bone marrow aspiration

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003658.htm Bone marrow aspiration To use the sharing features on this page, please enable JavaScript. Bone marrow is the soft tissue inside bones that helps ...

  12. Bone density scan (image)

    MedlinePlus

    ... bone the higher the risk of fractures. A bone scan, along with a patient's medical history, is a ... and whether any preventative treatment is needed. A bone density scan has the advantage of being painless and exposing ...

  13. Smoking and Bone Health

    MedlinePlus

    ... direct relationship between tobacco use and decreased bone density. Analyzing the impact of cigarette smoking on bone ... hard to determine whether a decrease in bone density is due to smoking itself or to other ...

  14. Menopause and Bone Loss

    MedlinePlus

    ... You reach your highest bone mass (size and density) at about age 30. Then, sometime between age ... your bones, your doctor may do a bone density test (DEXA scan). This test gives exact measurements ...

  15. [Evaluation of bone sterngth].

    PubMed

    Mashiba, Tasuku

    2016-01-01

    Biomechanical testing of the bone provides the most important and direct information about bone strength. This article explains biomechanical priciples including structural mechanical properties and intrinsic material properties, and serves actual biomechanical testing tedhniques for bone specimens. PMID:26728529

  16. Bone marrow biopsy

    MedlinePlus

    Biopsy - bone marrow ... A bone marrow biopsy may be done in the health care provider's office or in a hospital. The sample may be taken from the pelvic or breast bone. Sometimes, other areas are used. Marrow is removed ...

  17. Strategic approaches to adverse outcome pathway development

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are conceptual frameworks for organizing biological and toxicological knowledge in a manner that supports extrapolation of data pertaining to the initiation or early progression of toxicity to an apical adverse outcome that occurs at a level of org...

  18. Adverse Drug Reactions in Dental Practice

    PubMed Central

    Becker, Daniel E.

    2014-01-01

    Adverse reactions may occur with any of the medications prescribed or administered in dental practice. Most of these reactions are somewhat predictable based on the pharmacodynamic properties of the drug. Others, such as allergic and pseudoallergic reactions, are less common and unrelated to normal drug action. This article will review the most common adverse reactions that are unrelated to drug allergy. PMID:24697823

  19. Adverse drug reactions and organ damage: The skin.

    PubMed

    Marzano, Angelo V; Borghi, Alessandro; Cugno, Massimo

    2016-03-01

    Cutaneous adverse drug reactions are frequent, affecting 2-3% of hospitalized patients and in one twentieth of them are potentially life-threatening. Almost any pharmacologic agent can induce skin reactions, and certain drug classes, such as non-steroidal anti-inflammatory drugs, antibiotics and antiepileptics, have drug eruption rates ranging from 1% to 5%. Cutaneous drug reactions recognize several different pathomechanisms: some skin manifestations are immune-mediated like allergic reactions while others are the result of non immunological causes such as cumulative toxicity, photosensitivity, interaction with other drugs or different metabolic pathways. Cutaneous adverse drug reactions can be classified into two groups: common non-severe and rare life-threatening adverse drug reactions. Non-severe reactions are often exanthematous or urticarial whereas life-threatening reactions typically present with skin detachment or necrosis of large areas of the body and mucous membrane involvement, as in the Stevens-Johnson syndrome or toxic epidermal necrolysis. Clinicians should carefully evaluate the signs and symptoms of all cutaneous adverse drug reactions thought to be due to drugs and immediately discontinue drugs that are not essential. Short cycles of systemic corticosteroids in combination with antihistamines may be necessary for widespread exanthematous rashes, while more aggressive corticosteroid regimens or intravenous immunoglobulins associated with supportive treatment should be used for patients with Stevens-Johnson syndrome or toxic epidermal necrolysis. PMID:26674736

  20. DYSAPOPTOSIS OF OSTEOBLASTS AND OSTEOCYTES INCREASES CANCELLOUS BONE FORMATION BUT EXAGGERATES BONE POROSITY WITH AGE

    PubMed Central

    Jilka, Robert L.; O’Brien, Charles A.; Roberson, Paula K.; Bonewald, Lynda F.; Weinstein, Robert S.; Manolagas, Stavros C.

    2013-01-01

    Skeletal aging is accompanied by decreased cancellous bone mass and increased formation of pores within cortical bone. The latter accounts for a large portion of the increase in non-vertebral fractures after age 65 in humans. We selectively deleted Bak and Bax, two genes essential for apoptosis, in two types of terminally differentiated bone cells: the short-lived osteoblasts that elaborate the bone matrix, and the long-lived osteocytes that are immured within the mineralized matrix and choreograph the regeneration of bone. Attenuation of apoptosis in osteoblasts increased their working lifespan and thereby cancellous bone mass in the femur. In long-lived osteocytes, however, it caused dysfunction with advancing age and greatly magnified intracortical femoral porosity associated with increased production of receptor activator of nuclear factor-κB ligand and vascular endothelial growth factor. Increasing bone mass by artificial prolongation of the inherent lifespan of short-lived osteoblasts, while exaggerating the adverse effects of aging on long-lived osteocytes, highlights the seminal role of cell age in bone homeostasis. In addition, our findings suggest that distress signals produced by old and/or dysfunctional osteocytes are the culprits of the increased intracortical porosity in old age. PMID:23761243

  1. Bone cells, sclerostin, and FGF23: what's bred in the bone will come out in the flesh.

    PubMed

    Ott, Susan M

    2015-03-01

    Bone metabolism is linked to systemic diseases, and new research shows that the bone cells have endocrine functions that affect multiple organs. They secrete sclerostin, FGF23, prostaglandins, and osteocalcin. Pereira et al. examined gene expression of cells grown from bone biopsies of adolescents with renal osteodystrophy, as a first step to understanding how the bone-cell abnormalities contribute to cardiovascular and metabolic problems in these patients. PMID:25723633

  2. In vivo assessment of new resorbable PEG-PPG-PEG copolymer/starch bone wax in bone healing and tissue reaction of bone defect in rabbit model.

    PubMed

    Suwanprateeb, J; Kiertkrittikhoon, S; Kintarak, J; Suvannapruk, W; Thammarakcharoen, F; Rukskul, P

    2014-09-01

    In this study, in vivo performance of novel resorbable bone wax based on a miscible blend between PEG-PPG-PEG copolymer mixtures and pregelatinized starch at 0 and 25 percent by weight including hemostasis, tissue reaction and bone healing in a non-critical size tibia defect model were assessed and compared with commercial non-resorbable bone wax. Systemic reaction was evaluated by blood chemistry while local reaction, bone quantity and quality were evaluated by microcomputed tomography (microCT) and histology analyses. It was observed that the resorbable bone waxes did not show any adverse systemic reaction and resorbed from the defects within approximately 2 days after application. They were as effective as the commercial bone wax in hemostasis, but provided better adherence to the bone surface. The incorporation of pre-gelatinized starch in the formulation could further help in improved molding texture and decreased glove adherence. MicroCT and histology analyses showed that the resorbable bone waxes did not inhibit the osteogenesis whereas commercial bone wax impaired bone healing and displayed inflammation and foreign body reactions. PMID:24913421

  3. Nurses must report adverse drug reactions.

    PubMed

    Griffith, Richard

    There is renewed determination throughout the European Union (EU) to reduce the economic cost and high death rate associated with adverse drug reactions through better pharmacovigilance. Timely reporting and sharing of information concerning adverse drug reactions is vital to the success of this initiative. In the UK, the reporting of serious adverse drug reactions is facilitated by the Yellow Card Scheme, yet despite being well placed to monitor the effect of medicines on patients, nurses do not make full use of the scheme. This article sets out the impact of adverse drug reactions in the EU and argues that it is essential that nurses must be at the vanguard of adverse reaction reporting if the EU's pharmacovigilance initiative is to be a success. PMID:23905231

  4. Adulthood personality correlates of childhood adversity

    PubMed Central

    Carver, Charles S.; Johnson, Sheri L.; McCullough, Michael E.; Forster, Daniel E.; Joormann, Jutta

    2014-01-01

    Objective: Childhood adversity has been linked to internalizing and externalizing disorders and personality disorders in adulthood. This study extends that research by examining several personality measures as correlates of childhood adversity. Method: In a college sample self-reports were collected of childhood adversity, several scales relating to personality, and current depression symptoms as a control variable. The personality-related scales were reduced to four latent variables, which we termed anger/aggression, extrinsic focus, agreeableness, and engagement. Results: Controlling for concurrent depressive symptoms and gender, higher levels of reported childhood adversity related to lower agreeableness and to higher anger/aggression and extrinsic focus. Conclusions: Findings suggest that early adversity is linked to personality variables relevant to the building of social connection. PMID:25484874

  5. Bone-density changes after stroke.

    PubMed

    Beaupre, Gary S; Lew, Henry L

    2006-05-01

    It has been many years since bone loss and fracture risk were first recognized as serious complications of stroke. Hip fracture is associated with a substantial increase in morbidity and mortality for stroke survivors, and therefore, assessing and maintaining skeletal health after stroke should be an important clinical goal. Recent long-term, prospective studies have illustrated a highly nonuniform pattern of bone changes after stroke. In general, there is significant bone loss on the paretic side, which is greatest in those patients with the most severe functional deficits. In some patients, bone loss in the paretic arm during the first year after stroke is the equivalent of >20 yrs of bone loss in healthy individuals of comparable age. Bone density in the nonparetic upper limb can actually increase after stroke, consistent with an increase in habitual use of the nonparetic hand. Bone density in the paretic lower limb can decrease by >10% in <1 yr, with smaller decreases being typical for the nonparetic lower limb. Despite the recent increase in the number of prospective, longitudinal studies, important questions about bone changes after stroke remain unanswered. Longer-term studies quantifying bone loss for periods of >12 mos poststroke are needed to determine how long excess bone loss continues after stroke. Studies with more subjects and with more varied disability levels are needed to better understand the relationships between functional deficits and bone loss. New metrics are needed to quantify the intensity and duration of physical activity in the upper and lower limbs that are consistent with previous research on the role of mechanical stimuli in bone adaptation. Finally, an assessment of skeletal health and the factors that affect bone quantity and quality should be a standard component in the clinical management of all survivors of stroke. PMID:16628156

  6. Understanding adverse events: human factors.

    PubMed Central

    Reason, J

    1995-01-01

    (1) Human rather than technical failures now represent the greatest threat to complex and potentially hazardous systems. This includes healthcare systems. (2) Managing the human risks will never be 100% effective. Human fallibility can be moderated, but it cannot be eliminated. (3) Different error types have different underlying mechanisms, occur in different parts of the organisation, and require different methods of risk management. The basic distinctions are between: Slips, lapses, trips, and fumbles (execution failures) and mistakes (planning or problem solving failures). Mistakes are divided into rule based mistakes and knowledge based mistakes. Errors (information-handling problems) and violations (motivational problems) Active versus latent failures. Active failures are committed by those in direct contact with the patient, latent failures arise in organisational and managerial spheres and their adverse effects may take a long time to become evident. (4) Safety significant errors occur at all levels of the system, not just at the sharp end. Decisions made in the upper echelons of the organisation create the conditions in the workplace that subsequently promote individual errors and violations. Latent failures are present long before an accident and are hence prime candidates for principled risk management. (5) Measures that involve sanctions and exhortations (that is, moralistic measures directed to those at the sharp end) have only very limited effectiveness, especially so in the case of highly trained professionals. (6) Human factors problems are a product of a chain of causes in which the individual psychological factors (that is, momentary inattention, forgetting, etc) are the last and least manageable links. Attentional "capture" (preoccupation or distraction) is a necessary condition for the commission of slips and lapses. Yet, its occurrence is almost impossible to predict or control effectively. The same is true of the factors associated with

  7. Appropriate use of bone densitometry

    SciTech Connect

    Genant, H.K.; Block, J.E.; Steiger, P.; Glueer, C.C.; Ettinger, B.; Harris, S.T.

    1989-03-01

    The authors discuss current capabilities of three common bone densitometry techniques--single photon absorptiometry, dual photon absorptiometry, and quantitative computed tomography--and potential capabilities of new innovations of each of these techniques. They believe that use of bone densitometry is valid in the following four clinical applications and recommend its usage to (a) assess patients with metabolic diseases known to affect the skeleton, (b) assess perimenopausal women for initiation of estrogen replacement therapy, (c) establish a diagnosis of osteoporosis or assess its severity in the context of general clinical care, and (d) monitor the efficacy of treatment interventions or the natural course of disease.

  8. Bone marrow transplant - discharge

    MedlinePlus

    Transplant - bone marrow - discharge; Stem cell transplant - discharge; Hematopoietic stem cell transplant - discharge; Reduced intensity; Non-myeloablative transplant - discharge; Mini transplant - discharge; Allogenic bone marrow transplant - ...

  9. The use of demineralized laminar bone sheets in guided bone regeneration procedures: report of three cases.

    PubMed

    Fugazzotto, P A

    1996-01-01

    Demineralized laminar bone sheets were utilized as membranes to affect guided bone regeneration around five implants in two patients and to perform a ridge augmentation procedure in one patient. In all cases, significant regeneration of hard tissues occurred, and no complications were encountered. The regenerated hard tissues have been in function for up to 32 months with no clinical signs of breakdown. PMID:8666457

  10. Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament.

    PubMed

    Kuhn, Manuel; Scharfenort, Robert; Schümann, Dirk; Schiele, Miriam A; Münsterkötter, Anna L; Deckert, Jürgen; Domschke, Katharina; Haaker, Jan; Kalisch, Raffael; Pauli, Paul; Reif, Andreas; Romanos, Marcel; Zwanzger, Peter; Lonsdorf, Tina B

    2016-04-01

    Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences. PMID:26568620

  11. Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament

    PubMed Central

    Kuhn, Manuel; Scharfenort, Robert; Schümann, Dirk; Schiele, Miriam A.; Münsterkötter, Anna L.; Deckert, Jürgen; Domschke, Katharina; Haaker, Jan; Kalisch, Raffael; Pauli, Paul; Reif, Andreas; Romanos, Marcel; Zwanzger, Peter

    2016-01-01

    Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences. PMID:26568620

  12. Bone demineralization

    NASA Technical Reports Server (NTRS)

    Mack, P. B.; Vose, G. P.; Vogt, F. B.; Lachance, P. A.

    1971-01-01

    Crew members of the Gemini 4, Gemini 5, and Gemini 7 missions were compared regarding skeletal changes in three major anatomic sites with respect to changes in skeletal density during space flight. Bone-mass changes have been found for the command pilot and the pilot of each mission in the conventional os calcis section, in the combined sections covering 60 percent of the os calcis, and in hand phalanges 5-2 and 4-2. Comparison of radiographically determined losses in X-ray absorbence with X-ray absorbence losses in healthy young men subjected to bedrest immobilization for the same length of time showed that losses for the crewmembers exceeded losses for the bedrest subjects in all cases; this was an indication that restriction of body movement did not represent the only factor involved.

  13. Exercise, lifestyle, and your bones

    MedlinePlus

    Osteoporosis - exercise; Low bone density - exercise ... Osteoporosis is a disease that causes bones to become brittle and more likely to fracture (break). With osteoporosis, the bones lose density. Bone density is the amount of bone ...

  14. Calcium requirements of growing rats based on bone mass, structure, or biomechanical strength are similar

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although calcium (Ca) supplementation increases bone density, the increase is small and the impact on bone strength and fracture risk is uncertain. To investigate if bone mass, morphology, and biomechanical properties are affected by deficient to copious dietary Ca concentrations, the long bones (ti...

  15. Narghile smoking and its adverse health consequences: a literature review.

    PubMed

    Dar-Odeh, N S; Abu-Hammad, O A

    2009-06-13

    Oral squamous cell carcinoma (OSCC) is a world health problem with approximately 50% of patients having a 5-year survival rate. A change in the demographics of the disease is now being recognised, particularly in Europe, where it is increasingly being seen in young males. While a variety of risk factors are important in OSCC, it is tobacco that plays a central part in the pathogenesis of the disease. Narghile is an old form of tobacco use but in the past decade, there has been a resurgence in this form of smoking. The practice is particularly common in young males and females from the Middle East but with the advent of immigration and globalisation, its use is becoming more widespread. It is now not uncommon to see narghile smoking in western countries such as the UK and USA. Studies describing the oral effects of narghile are unfortunately scarce. While adverse effects such as periodontal bone loss and dry socket have been described, its association with OSCC cannot be excluded. Variation in the type of narghile, the type of tobacco and the presence of co-factors such as cigarette smoking may all influence clinical outcome. In the present study, the practice of narghile smoking is reviewed in terms of its effect on health, particularly oral health. The association of narghile smoking and adverse effects on the orofacial region will be outlined, namely, periodontal disease, potentially malignant lesions and oral cancer. PMID:19521371

  16. Adverse Effects of Diabetes Mellitus on the Skeleton of Aging Mice.

    PubMed

    Portal-Núñez, Sergio; Ardura, Juan Antonio; Lozano, Daniel; Bolívar, Oskarina Hernández; López-Herradón, Ana; Gutiérrez-Rojas, Irene; Proctor, Alexander; van der Eerden, Bram; Schreuders-Koedam, Marijke; van Leeuwen, Johannes; Alcaraz, María José; Mulero, Francisca; de la Fuente, Mónica; Esbrit, Pedro

    2016-03-01

    In the present study, the possibility that a diabetic (DM) status might worsen age-related bone deterioration was explored in mice. Male CD-1 mice aged 2 (young control group) or 16 months, nondiabetic or made diabetic by streptozotocin injections, were used. DM induced a decrease in bone volume, trabecular number, and eroded surface, and in mineral apposition and bone formation rates, but an increased trabecular separation, in L1-L3 vertebrae of aged mice. Three-point bending and reference point indentation tests showed slight changes pointing to increased frailty and brittleness in the mouse tibia of diabetic old mice. DM was related to a decreased expression of both vascular endothelial growth factor and its receptor 2, which paralleled that of femoral vasculature, and increased expression of the pro-adipogenic gene peroxisome proliferator-activated receptor γ and adipocyte number, without affecting β-catenin pathway in old mouse bone. Concomitant DM in old mice failed to affect total glutathione levels or activity of main anti-oxidative stress enzymes, although xanthine oxidase was slightly increased, in the bone marrow, but increased the senescence marker caveolin-1 gene. In conclusion, DM worsens bone alterations of aged mice, related to decreased bone turnover and bone vasculature and increased senescence, independently of the anti-oxidative stress machinery. PMID:26386012

  17. Collateral Adverse Outcomes After Lumbar Spine Surgery.

    PubMed

    Daniels, Alan H; Gundle, Kenneth; Hart, Robert A

    2016-01-01

    Collateral adverse outcomes are the expected or unavoidable results of a procedure that is performed in a standard manner and typically experienced by the patient. Collateral adverse outcomes do not result from errors, nor are they rare. Collateral adverse outcomes occur as the direct result of a surgical procedure and must be accepted as a trade-off to attain the intended benefits of the surgical procedure. As such, collateral adverse outcomes do not fit into the traditional definition of a complication or adverse event. Examples of collateral adverse outcomes after lumbar spine arthrodesis include lumbar stiffness, postoperative psychological stress, postoperative pain, peri-incisional numbness, paraspinal muscle denervation, and adjacent-level degeneration. Ideally, a comparison of interventions for the treatment of a clinical condition should include information on both the negative consequences (expected and unexpected) and potential benefits of the treatment options. The objective evaluation and reporting of collateral adverse outcomes will provide surgeons with a more complete picture of invasive interventions and, thus, the improved ability to assess alternative treatment options. PMID:27049197

  18. Adverse event recording post hip fracture surgery.

    PubMed

    Doody, K; Mohamed, K M S; Butler, A; Street, J; Lenehan, B

    2013-01-01

    Accurate recording of adverse events post hip fracture surgery is vital for planning and allocating resources. The purpose of this study was to compare adverse events recorded prospectively at point of care with adverse recorded by the Hospital In-Patient Enquiry (HIPE) System. The study examined a two month period from August to September 2011 at University Hospital Limerick. Out of a sample size of 39, there were 7 males (17.9%) and 32 females (82.1%) with an age range of between 53 and 98 years. The mean age was 80.5 years. 55 adverse events were recorded, in contrast to the HIPE record of 13 (23.6%) adverse events. The most common complications included constipation 10 (18.2%), anaemia 8 (14.5%), urinary retention 8 (14.50%), pneumonia 5 (9.1%) and delirium 5 (9.1%). Of the female cohort, 24 (68.8%) suffered an adverse event, while only 4 (57%) males suffered an adverse event. PMID:24579408

  19. Genetics of pediatric bone strength.

    PubMed

    Mitchell, Jonathan A; Cousminer, Diana L; Zemel, Babette S; Grant, Struan F A; Chesi, Alessandra

    2016-01-01

    Osteoporosis is one of the most common chronic forms of disability in postmenopausal women and represents a major health burden around the world. Bone fragility is affected by bone mineral density (BMD), and, one of the most important factors in preventing osteoporosis is optimizing peak bone mass, which is achieved during growth in childhood and adolescence. BMD is a complex trait resulting from environmental and genetic factors. Genome-wide association studies have discovered robust genetic signals influencing BMD in adults, and similar studies have also been conducted to investigate the genetics of BMD in the pediatric setting. These latter studies have revealed that many adult osteoporosis-related loci also regulate BMD during growth. These investigations have the potential to profoundly impact public health and will allow for the eventual development of effective interventions for the prevention of osteoporosis. PMID:27579163

  20. Adverse childhood event experiences, fertility difficulties, and menstrual cycle characteristics

    PubMed Central

    Jacobs, Marni B.; Boynton-Jarrett, Renee D.; Harville, Emily W.

    2016-01-01

    Introduction Increased childhood adversity may be affect adult fertility, however, the mechanism through which this occurs is unclear. Menstrual cycle abnormalities are predictive of fertility difficulties, and stress influences menstrual cycle characteristics. Here, we assesses whether adverse childhood experiences (ACEs) are associated with fertility difficulties and menstrual cycle dysregulation, offering a plausible mechanism for the link between lifetime stress and fertility. Methods From April 2012 – February 2014, 742 pregnant and non-pregnant women aged 18–45 years residing in southeastern Louisiana provided information on childhood adversity and reproductive history. Associations between ACEs and fertility difficulties and menstrual cycle patterns were evaluated. Results As the number of ACEs increased, risk of fertility difficulties and amenorrhea increased (RR = 1.09, 95% CI 1.05 – 1.13 and RR = 1.07, 95% CI 1.04 – 1.10, respectively), while fecundability decreased (FR = 0.97, 95% CI 0.95 – 1.00). Compared to women with no adversity, women in the high adversity group were more likely to experience both infertility and amenorrhea (RR = 2.75, 95% CI 1.45 – 5.21 and RR = 2.54, 95% CI 1.52 – 4.25, respectively), and reduced fecundability (FR = 0.75, 95% CI 0.56 – 1.00). Although similar patterns were seen for menstrual cycle irregularity, associations were diminished. Associations did not materially change following adjustment for age, BMI, race, education, smoking, and income. Results are constrained by the self-report nature of the study and the limited generalizability of the study population. Discussion To our knowledge, this is the first study to present evidence of a link between childhood stressors, menstrual cycle disruption, and fertility difficulties. The effect of childhood stress on fertility may be mediated through altered functioning of the HPA axis, acting to suppress fertility in response to less than optimal reproductive

  1. Learning from adverse incidents involving medical devices.

    PubMed

    Amoore, John; Ingram, Paula

    While an adverse event involving a medical device is often ascribed to either user error or device failure, the causes are typically multifactorial. A number of incidents involving medical devices are explored using this approach to investigate the various causes of the incident and the protective barriers that minimised or prevented adverse consequences. User factors, including mistakes, omissions and lack of training, conspired with background factors--device controls and device design, storage conditions, hidden device damage and physical layout of equipment when in use--to cause the adverse events. Protective barriers that prevented or minimised the consequences included staff vigilance, operating procedures and alarms. PMID:12715578

  2. Uncertainty Comparison of Visual Sensing in Adverse Weather Conditions.

    PubMed

    Lo, Shi-Wei; Wu, Jyh-Horng; Chen, Lun-Chi; Tseng, Chien-Hao; Lin, Fang-Pang; Hsu, Ching-Han

    2016-01-01

    This paper focuses on flood-region detection using monitoring images. However, adverse weather affects the outcome of image segmentation methods. In this paper, we present an experimental comparison of an outdoor visual sensing system using region-growing methods with two different growing rules-namely, GrowCut and RegGro. For each growing rule, several tests on adverse weather and lens-stained scenes were performed, taking into account and analyzing different weather conditions with the outdoor visual sensing system. The influence of several weather conditions was analyzed, highlighting their effect on the outdoor visual sensing system with different growing rules. Furthermore, experimental errors and uncertainties obtained with the growing rules were compared. The segmentation accuracy of flood regions yielded by the GrowCut, RegGro, and hybrid methods was 75%, 85%, and 87.7%, respectively. PMID:27447642

  3. Uncertainty Comparison of Visual Sensing in Adverse Weather Conditions†

    PubMed Central

    Lo, Shi-Wei; Wu, Jyh-Horng; Chen, Lun-Chi; Tseng, Chien-Hao; Lin, Fang-Pang; Hsu, Ching-Han

    2016-01-01

    This paper focuses on flood-region detection using monitoring images. However, adverse weather affects the outcome of image segmentation methods. In this paper, we present an experimental comparison of an outdoor visual sensing system using region-growing methods with two different growing rules—namely, GrowCut and RegGro. For each growing rule, several tests on adverse weather and lens-stained scenes were performed, taking into account and analyzing different weather conditions with the outdoor visual sensing system. The influence of several weather conditions was analyzed, highlighting their effect on the outdoor visual sensing system with different growing rules. Furthermore, experimental errors and uncertainties obtained with the growing rules were compared. The segmentation accuracy of flood regions yielded by the GrowCut, RegGro, and hybrid methods was 75%, 85%, and 87.7%, respectively. PMID:27447642

  4. Chemical research on red pigments after adverse reactions to tattoo.

    PubMed

    Tammaro, A; Toniolo, C; Giulianelli, V; Serafini, M; Persechino, S

    2016-03-01

    Currently, the incidence of tattooing is on the rise compared to the past, especially among adolescents, and it leads to the urgency of monitoring the security status of tattooing centers, as well as to inform people about the risks of tattoo practice. In our clinical experience, 20% of tattooed patients presented adverse reactions, like allergic contact dermatitis, psoriasis with Koebner's phenomena and granulomatous reactions, with the latter most prevalent and most often related to red pigment. Adverse reactions to tattoo pigments, especially the red one, are well known and described in literature. Great attention has to be focused on the pigments used, especially for the presence of new substances, often not well known. For this reason, we decided to perform a study on 12 samples of red tattoo ink, obtained by patients affected by different cutaneous reactions in the site of tattoo, to analyze their chemical composition. PMID:26934738

  5. Bone turnover in early rheumatoid arthritis. 2. Longitudinal bone density studies.

    PubMed Central

    Sambrook, P N; Ansell, B M; Foster, S; Gumpel, J M; Hesp, R; Reeve, J

    1985-01-01

    Serial measurements of bone mineral in 17 ambulant female patients with rheumatoid arthritis (RA) of recent onset and 19 age matched female controls were made in the radius by computed tomography and in the vertebrae by dual photon absorptiometry. Loss of trabecular bone from the distal radius was more rapid in RA (p = 0.0014), but there was no difference in the rate of loss of bone mineral from the radial midshaft or lumbar spine compared with the controls. This study is consistent with the hypothesis that the predominant form of bone loss early in the disease is the vicinity of affected joints. PMID:3876077

  6. Adverse Effects of Wheat Gluten.

    PubMed

    Koning, Frits

    2015-01-01

    Man began to consume cereals approximately 10,000 years ago when hunter-gatherers settled in the fertile golden crescent in the Middle East. Gluten has been an integral part of the Western type of diet ever since, and wheat consumption is also common in the Middle East, parts of India and China as well as Australia and Africa. In fact, the food supply in the world heavily depends on the availability of cereal-based food products, with wheat being one of the largest crops in the world. Part of this is due to the unique properties of wheat gluten, which has a high nutritional value and is crucial for the preparation of high-quality dough. In the last 10 years, however, wheat and gluten have received much negative attention. Many believe that it is inherently bad for our health and try to avoid consumption of gluten-containing cereals; a gluten-low lifestyle so to speak. This is fueled by a series of popular publications like Wheat Belly; Lose the Wheat, Lose the Weight, and Find Your Path Back to Health. However, in reality, there is only one condition where gluten is definitively the culprit: celiac disease (CD), affecting approximately 1% of the population in the Western world. Here, I describe the complexity of the cereals from which gluten is derived, the special properties of gluten which make it so widely used in the food industry, the basis for its toxicity in CD patients and the potential for the development of safe gluten and alternatives to the gluten-free diet. PMID:26606684

  7. Metabolic bone disease associated with total parenteral nutrition.

    PubMed

    Klein, G L; Coburn, J W

    1984-01-01

    Patients receiving long-term treatment with total parenteral nutrition often develop bony abnormalities characterized by patchy osteomalacia and low bone turnover. The patients present evidence of physiologic hypoparathyroidism, although low levels of iPTH cannot entirely explain the osteomalacia. Abnormally low serum levels of 1,25(OH)2-vitamin D have been demonstrated, but the significance of these reduced levels in the pathogenesis of the bone lesions is not defined. Aluminum has been detected in large quantities in the plasma, urine, and bone of some patients treated with TPN, and there is mounting evidence that aluminum may be associated with skeletal pathology, particularly osteomalacia. There is, however, no clear documentation that aluminum accumulation produces the skeletal lesions observed, although it could be a contributing factor. There has been the unusual empiric observation that the removal of vitamin D2 from the infusate is associated with a decrease in the quantity of unmineralized osteoid in TPN patients. A possible role of vitamin D2 in producing osteomalacia is not easy to understand since normal serum levels of 25(OH)-D2, the circulating form of vitamin D2, have been reported. The long-term consequences of intravenous nutritional support for many aspects of metabolism remain unknown. Administration into the systemic circulation of predetermined quantities of calcium and phosphorus via a route that bypasses their passage across the intestinal mucosa, the portal system and the liver may have adverse consequences. It is possible that bypassing homeostatic mechanisms may affect bone formation and metabolism or lead to alterations in vitamin D sterols. Alternatively, a deficiency of an essential trace metal or the accumulation of a toxic trace substance could be responsible for the bony abnormalities. Much remains to be clarified concerning calcium homeostasis and bone disease during total parenteral nutrition. Among various possible factors, it

  8. High-fat diet causes bone loss in young mice by promoting osteoclastogenesis through alteration of the bone marrow environment.

    PubMed

    Shu, Lei; Beier, Eric; Sheu, Tzong; Zhang, Hengwei; Zuscik, Michael J; Puzas, Edward J; Boyce, Brendan F; Mooney, Robert A; Xing, Lianping

    2015-04-01

    Obesity is a severe health problem in children, afflicting several organ systems including bone. However, the role of obesity on bone homeostasis and bone cell function in children has not been studied in detail. Here we used young mice fed a high-fat diet (HFD) to model childhood obesity and investigate the effect of HFD on the phenotype of cells within the bone marrow environment. Five-week-old male mice were fed a HFD for 3, 6, and 12 weeks. Decreased bone volume was detected after 3 weeks of HFD treatment. After 6 and 12 weeks, HFD-exposed mice had less bone mass and increased osteoclast numbers. Bone marrow cells, but not spleen cells, from HFD-fed mice had increased osteoclast precursor frequency, elevated osteoclast formation, and bone resorption activity, as well as increased expression of osteoclastogenic regulators including RANKL, TNF, and PPAR-gamma. Bone formation rate and osteoblast and adipocyte numbers were also increased in HFD-fed mice. Isolated bone marrow cells also had a corresponding elevation in the expression of positive regulators of osteoblast and adipocyte differentiation. Our findings indicate that in juvenile mice, HFD-induced bone loss is mainly due to increased osteoclast bone resorption by affecting the bone marrow microenvironment. Thus, targeting osteoclast formation may present a new therapeutic approach for bone complications in obese children. PMID:25673503

  9. Targeted radiotherapy of bone malignancies.

    PubMed

    Jansen, David R; Krijger, Gerard C; Kolar, Zvonimir I; Zonnenberg, Bernard A; Zeevaart, Jan Rijn

    2010-12-01

    The severe pain associated with many disorders affecting bone account for a large proportion of cases of patient morbidity, due to the encumbrance of mobility and therefore, compromised quality of life. Skeletal metastasis is one such condition, which generally complicates the treatment of the primary cancers such as that of the breast, prostate and lung - causing intense pain and eventually even mortality. This paper presents examples of various approaches explored and proposed in the ongoing search to identify better radiopharmaceuticals for the treatment of bone disorders such as metastases. The primary objective of these developments is to alleviate the debilitating pain commonly associated with bone lesions. The efficacy of a radiotherapeutic agent intended for the treatment of diseased bone is particularly dependent on the radiation dose to the tumor cells and on the extent to which suppression of bone marrow or other critical organs can be avoided. Therefore, the design rationale requires careful consideration of the choice radionuclide and especially ensuring that the drug selectively targets the lesion or tumor site. The options pursued include the use of radioisotopes with an intrinsic affinity for bone, such as (89)Sr or (223)Ra, or the design of bone-seeking ligands, such as phosphonates, to selectively deliver the radionuclide to the target, e.g. [(153)Sm]Sm-EDTMP. A combination of the above may too be possible, where the bone seeking ligand facilitates the selective accumulation of a radionuclide, which by itself is also bone homing. In terms of therapeutic application radionuclides with various decay modes are proposed, including beta (-) emitters: (153)Sm, (89)Sr, (186)Re, (188)Re, (32)P, (177)Lu and (170)Tm; alpha (α) emitters: (223)Ra and (225)Ra; and Auger or conversion electron emitter: (117)mSn. From a purely diagnostic perspective, the radioisotopes used for imaging include the well known photon emitting (99)mTc, and positron emitters (18)F

  10. Bone scan appearances following biopsy of bone and bone marrow

    SciTech Connect

    McKillop, J.H.; Maharaj, D.; Boyce, B.F.; Fogelman, I.

    1984-10-01

    The influence of sternal marrow aspiration, iliac crest marrow aspiration, and iliac crest bone biopsy on bone scan appearances was examined. Eighteen patients were scanned a mean of 9.9 days after sternal marrow aspiration with a Salah needle. Bone scans obtained in 9 patients a mean of 10 days aftr iliac crest trephine marrow biopsy with a Jamshidi needle showed no abnormality at the biopsy site. In 18 patients with metabolic bone disease who had undergone iliac crest bone biopsy with an 8 mm needle, a scan abnormality due to the biopsy was usually present when the interval between the biopsy and the scan was 5 days to 2 months. Patients who were scanned within 3 days of iliac crest bone biopsy or more than 2 months after biopsy had normal scan appearance at the biopsy site.

  11. Bone grafts in dentistry

    PubMed Central

    Kumar, Prasanna; Vinitha, Belliappa; Fathima, Ghousia

    2013-01-01

    Bone grafts are used as a filler and scaffold to facilitate bone formation and promote wound healing. These grafts are bioresorbable and have no antigen-antibody reaction. These bone grafts act as a mineral reservoir which induces new bone formation. PMID:23946565

  12. Bone Marrow Transplantation

    MedlinePlus

    Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. It contains immature cells, called stem cells. The ... platelets, which help the blood to clot. A bone marrow transplant is a procedure that replaces a ...

  13. Effects of simulated weightlessness on bone mineral metabolism

    NASA Technical Reports Server (NTRS)

    Globus, R. K.; Bikle, D. D.; Morey-Holton, E.

    1984-01-01

    It is pointed out that prolonged space flight, bedrest, and immobilization are three factors which can produce a negative calcium balance, osteopenia, and an inhibition of bone formation. It is not known whether the effects of gravity on bone mineral metabolism are mediated by systemic endocrine factors which affect all bones simultaneously, or by local factors which affect each bone individually. The present investigation has the objective to test the relative importance of local vs. systemic factors in regulating the bone mineral response to conditions simulating weightlessness. Experiments were conducted with male Sprague-Dawley rats. The test conditions made it possible to compare the data from weighted and unweighted bones in the same animal. The obtained findings indicate that a decrease in bone mass relative to control value occurs rapidly under conditions which simulate certain aspects of weightlessness. However, this decrease reaches a plateau after 10 days.

  14. Adverse Outcome Pathways: From Definition to Application

    EPA Science Inventory

    A challenge for both human health and ecological toxicologists is the transparent application of mechanistic (e.g., molecular, biochemical, histological) data to risk assessments. The adverse outcome pathway (AOP) is a conceptual framework designed to meet this need. Specifical...

  15. Adverse cutaneous drug eruptions: current understanding.

    PubMed

    Hoetzenecker, W; Nägeli, M; Mehra, E T; Jensen, A N; Saulite, I; Schmid-Grendelmeier, P; Guenova, E; Cozzio, A; French, L E

    2016-01-01

    Adverse cutaneous drug reactions are recognized as being major health problems worldwide causing considerable costs for health care systems. Most adverse cutaneous drug reactions follow a benign course; however, up to 2% of all adverse cutaneous drug eruptions are severe and life-threatening. These include acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Physicians should be aware of specific red flags to rapidly identify these severe cutaneous drug eruptions and initiate appropriate treatment. Besides significant progress in clinical classification and treatment, recent studies have greatly enhanced our understanding in the pathophysiology of adverse cutaneous drug reactions. Genetic susceptibilities to certain drugs have been identified in SJS/TEN patients, viral reactivation in DRESS has been elucidated, and the discovery of tissue resident memory T cells helps to better understand the recurrent site-specific inflammation in patients with fixed drug eruption. PMID:26553194

  16. Childhood adversities and psychosis: evidence, challenges, implications

    PubMed Central

    Morgan, Craig; Gayer‐Anderson, Charlotte

    2016-01-01

    There is a substantial body of research reporting evidence of associations between various forms of childhood adversity and psychosis, across the spectrum from experiences to disorder. This has been extended, more recently, to include studies of cumulative effects, of interactions with other factors, of specific effects, and of putative biological and psychological mechanisms. In this paper we evaluate this research and highlight the remaining methodological issues and gaps that temper, but do not dismiss, conclusions about the causal role of childhood adversity. We also consider the emerging work on cumulative, synergistic, and specific effects and on mechanisms; and discuss the broader implications of this line of research for our understanding of psychosis. We conclude that the current balance of evidence is that childhood adversities – particularly exposure to multiple adversities involving hostility and threat – do, in some people, contribute to the onset of psychotic experiences and psychotic disorders. PMID:27265690

  17. RACIAL RESIDENTIAL SEGREGATION AND ADVERSE BIRTH OUTCOMES

    EPA Science Inventory

    INTRODUCTION. The disparity between black and white women's adverse birth outcomes has been subject to much investigation, yet the factors underlying its persistence remain elusive, which has encouraged research on neighborhood-level influences, including racial residential segr...

  18. Experiment K-6-05. The maturaton of bone and dentin matrices in rats flown on Cosmos 1887

    NASA Technical Reports Server (NTRS)

    Simmons, D.; Grynpas, M.; Rosenberg, G.; Durnova, G.

    1990-01-01

    The chemistry, hydroxyapatite crystal size, and maturation of the bone and dentin is characterized in rats exposed to microgravity for 12.5d in a Soviet Biosatellite (Cosmos-1887). Calvarial and vertebral bone ash was subnormal, but contained a normal percent composition of Ca, P, and Mg. These tissues varied from the norm by having lower Ca/P and higher Ca/Mg ratios than any of their age-matched controls (Vivarium and Synchronous Groups). Gradient density analyses (calvaria) indicated a strong shift to the lower sp.gr. fractions which was commensurate with impaired rates of matrix-mineral maturation. X-ray diffraction data were confirmatory. Bone hydroxyapatite crystal growth in Flight rats was preferentially altered in a way to reduce the dimension of their C-axis. Flight rat dentin was normal with respect to age-matched control Ca, P, Mg, and Zn concentrations and their Ca/P and Ca/Mg ratios. These observations affirm the concept that microgravity adversely affects the maturation of newly formed matrix and mineral moieties in bone.

  19. Heterogeneous glycation of cancellous bone and its association with bone quality and fragility.

    PubMed

    Karim, Lamya; Vashishth, Deepak

    2012-01-01

    Non-enzymatic glycation (NEG) and enzymatic biochemical processes create crosslinks that modify the extracellular matrix (ECM) and affect the turnover of bone tissue. Because NEG affects turnover and turnover at the local level affects microarchitecture and formation and removal of microdamage, we hypothesized that NEG in cancellous bone is heterogeneous and accounts partly for the contribution of microarchitecture and microdamage on bone fragility. Human trabecular bone cores from 23 donors were subjected to compression tests. Mechanically tested cores as well as an additional 19 cores were stained with lead-uranyl acetate and imaged to determine microarchitecture and measure microdamage. Post-yield mechanical properties were measured and damaged trabeculae were extracted from a subset of specimens and characterized for the morphology of induced microdamage. Tested specimens and extracted trabeculae were quantified for enzymatic and non-enzymatic crosslink content using a colorimetric assay and Ultra-high Performance Liquid Chromatography (UPLC). Results show that an increase in enzymatic crosslinks was beneficial for bone where they were associated with increased toughness and decreased microdamage. Conversely, bone with increased NEG required less strain to reach failure and were less tough. NEG heterogeneously modified trabecular microarchitecture where high amounts of NEG crosslinks were found in trabecular rods and with the mechanically deleterious form of microdamage (linear microcracks). The extent of NEG in tibial cancellous bone was the dominant predictor of bone fragility and was associated with changes in microarchitecture and microdamage. PMID:22514706

  20. Application of synchrotron radiation computed microtomography for quantification of bone microstructure in human and rat bones

    NASA Astrophysics Data System (ADS)

    Nogueira, Liebert Parreiras; Barroso, Regina Cély; de Almeida, André Pereira; Braz, Delson; de Almeida, Carlos Eduardo; de Andrade, Cherley Borba; Tromba, Giuliana

    2012-05-01

    This work aims to evaluate histomorphometric quantification by synchrotron radiation computed microto-mography in bones of human and rat specimens. Bones specimens are classified as normal and pathological (for human samples) and irradiated and non-irradiated samples (for rat ones). Human bones are specimens which were affected by some injury, or not. Rat bones are specimens which were irradiated, simulating radiotherapy procedures, or not. Images were obtained on SYRMEP beamline at the Elettra Synchrotron Laboratory in Trieste, Italy. The system generated 14 μm tomographic images. The quantification of bone structures were performed directly by the 3D rendered images using a home-made software. Resolution yielded was excellent what facilitate quantification of bone microstructures.