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  1. Determinants of relative skeletal maturity in South African children.

    Science.gov (United States)

    Hawley, Nicola L; Rousham, Emily K; Johnson, William; Norris, Shane A; Pettifor, John M; Cameron, Noël

    2012-01-01

    The variation of skeletal maturity about chronological age is a sensitive indicator of population health. Age appropriate or advanced skeletal maturity is a reflection of adequate environmental and social conditions, whereas delayed maturation suggests inadequate conditions for optimal development. There remains a paucity of data, however, to indicate which specific biological and environmental factors are associated with advancement or delay in skeletal maturity. The present study utilises longitudinal data from the South African Birth to Twenty (Bt20) study to indentify predictors of relative skeletal maturity (RSM) in early adolescence. A total of 244 black South African children (n=131 male) were included in this analysis. Skeletal maturity at age 9/10 years was assessed using the Tanner and Whitehouse III RUS technique. Longitudinal data on growth, socio-economic position and pubertal development were entered into sex-specific multivariable general linear regression models with relative skeletal maturity (skeletal age-chronological age) as the outcome. At 9/10 years of age males showed an average of 0.66 years delay in skeletal maturation relative to chronological age. Females showed an average of 1.00 year delay relative to chronological age. In males, being taller at 2 years (pdetermining the rate of skeletal maturation during childhood independently of current stature. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Assessment of skeletal maturation using mandibular second molar maturation stages.

    Science.gov (United States)

    Goyal, S; Goyal, S; Gugnani, N

    2014-01-01

    To investigate the relationship between cervical vertebrae maturation and mandibular second molar calcification stages. The study was designed as a retrospective, descriptive and crosssectional research project. Pre-treatment lateral cephalograms and panoramic radiographs of 99 males and 110 females in the age range of 7 to 18 years 7 months were evaluated with Demirjian Index (DI) and cervical vertebrae maturation indicators (CVMI) of Hassel and Farman. A null hypothesis was proposed that there is no relation between CVMI and DI. A highly significant association (Pearson's contingency coefficient 0.713 for males and 0.863 for females) was found between DI and CVMI. In males, the DI stage E corresponded to stage 2 of CVMI (pre-peak of pubertal growth spurt) and DI stages F and G corresponded to stages 3 and 4 of CVMI (peak of pubertal growth spurt). DI stage H was associated with stages 5 and 6 of CVMI (end of pubertal growth spurt). In females, the DI stages C, D corresponded to CVMI stages 1, 2; DI stages E, F with CVMI stages 3, 4; DI stages G, H with CVMI stages 5, 6. Mandibular second molar calcification stages can be used as indicators for assessment of skeletal maturity.

  3. Cervical vertebral maturation as a biologic indicator of skeletal maturity.

    Science.gov (United States)

    Santiago, Rodrigo César; de Miranda Costa, Luiz Felipe; Vitral, Robert Willer Farinazzo; Fraga, Marcelo Reis; Bolognese, Ana Maria; Maia, Lucianne Cople

    2012-11-01

    To identify and review the literature regarding the reliability of cervical vertebrae maturation (CVM) staging to predict the pubertal spurt. The selection criteria included cross-sectional and longitudinal descriptive studies in humans that evaluated qualitatively or quantitatively the accuracy and reproducibility of the CVM method on lateral cephalometric radiographs, as well as the correlation with a standard method established by hand-wrist radiographs. The searches retrieved 343 unique citations. Twenty-three studies met the inclusion criteria. Six articles had moderate to high scores, while 17 of 23 had low scores. Analysis also showed a moderate to high statistically significant correlation between CVM and hand-wrist maturation methods. There was a moderate to high reproducibility of the CVM method, and only one specific study investigated the accuracy of the CVM index in detecting peak pubertal growth. This systematic review has shown that the studies on CVM method for radiographic assessment of skeletal maturation stages suffer from serious methodological failures. Better-designed studies with adequate accuracy, reproducibility, and correlation analysis, including studies with appropriate sensitivity-specificity analysis, should be performed.

  4. A correlative study of dental age and skeletal maturation.

    Science.gov (United States)

    Sachan, Kiran; Sharma, Vijay Prakash; Tandon, Pradeep

    2011-01-01

    Skeletal age had been assessed by comparison between maturation of hand-wrist with stages of cervical vertebrae or canine calcification stages in past and this had been closely related to craniofacial growth. The importance of pubertal growth spurt in various types of orthodontic therapies is already established. Hence, this study was aimed to evaluate the relationship of skeletal maturity by hand-wrist with cervical vertebral maturation indicators and canine calcification stages. The study consisted of randomly selected 90 children from Lucknow population with 45 males (age range 10-13 years) and 45 females (age range 9-12 years). Lateral Cephalogram, hand-wrist x-ray, and periapical x-rays of maxillary and mandibular right canines were taken. Mean, standard deviation was calculated of different groups. Correlation was made among cervical vertebral maturation, hand wrist maturation, and canine calcification stages at various age groups. There was strong correlation between skeletal maturation indicator and cervical vertebral maturation indicator for both male (0.849) and female (0.932), whereas correlation between skeletal maturation indicator and canine calcification was good for both male and female (0.635, 0.891). It was concluded that cervical vertebral maturation indicator and canine calcification stages can also be used for assessing skeletal maturity.

  5. Skeletal maturity assessment using mandibular canine calcification stages

    Directory of Open Access Journals (Sweden)

    Vildana Džemidžić

    2016-11-01

    Full Text Available Objective. The aims of this study were: to investigate the relationship between mandibular canine calcification stages and skeletal maturity; and to evaluate whether the mandibular canine calcification stages may be used as a reliable diagnostic tool for skeletal maturity assessment. Materials and methods. This study included 151 subjects: 81 females and 70 males, with ages ranging from 9 to 16 years (mean age: 12.29±1.86 years. The inclusion criteria for subjects were as follows: age between 9 and 16 years; good general health without any hormonal, nutritional, growth or dental development problems. Subjects who were undergoing or had previously received orthodontic treatment were not included in this study. The calcification stages of the left permanent mandibular canine were assessed according to the method of Demirjian, on panoramic radiographs. Assessment of skeletal maturity was carried out using the cervical vertebral maturation index (CVMI, as proposed by the Hassel-Farman method, on lateral cephalograms. The correlation between the calcification stages of mandibular canine and skeletal maturity was estimated separately for male and female subjects. Results. Correlation coefficients between calcification stages of mandibular canine and skeletal maturity were 0.895 for male and 0.701 for female subjects. Conclusions. A significant correlation was found between the calcification stages of the mandibular canine and skeletal maturity. The calcification stages of the mandibular canine show a satisfactory diagnostic performance only for assessment of pre-pubertal growth phase.

  6. Roentgenographic indicators of skeletal maturity in marine mammals (Cetacea)

    International Nuclear Information System (INIS)

    Ogden, J.A.; Conlogue, G.J.; Rhodin, A.G.J.; Yale Univ., New Haven, CT

    1981-01-01

    A new roentgenographic classification (grading) scheme is presented for utilization in studies of skeletal development and maturation in marine mammals, particularly cetaceans. This is based on adequate description of the extent of development and maturation of the various secondary ossification centers, their eventual patterns of fusion, and subsequent remodeling with the metaphysis. The six stages are illustrated schematically and roentgenographically. This scheme may be applied to any cetacean longitudinal bone developing proximal and distal epiphyseal ossification centers. (orig.)

  7. Use of cervical vertebral maturation to determine skeletal age.

    Science.gov (United States)

    Wong, Ricky W K; Alkhal, Hessa A; Rabie, A Bakr M

    2009-10-01

    The purpose of this study was to evaluate the validity of the cervical vertebral maturation (CVM) method as an indicator of skeletal age in the circumpubertal period by correlating it to the hand-wrist method (HWM). Hand-wrist and lateral cephalometric radiographs of 400 Chinese subjects were randomly selected. Their ages were 10 to 15 years for girls and 12 to 17 years for boys, so they were within the circumpubertal period. Skeletal ages were assessed according to the CVM method and the HWM. The CVM was significantly correlated with HWM skeletal age (Spearman r = 0.9521 [boys] and 0.9408 [girls]). All patients in cervical vertebral stage 3 of the CVM corresponded to stages MP3-FG or MP3-G (around the peak of the growth spurt) in the HWM. The CVM is a valid indicator of skeletal growth during the circumpubertal period, providing information for timing of growth modification.

  8. Eruption of the maxillary canines in relation to skeletal maturity.

    Science.gov (United States)

    Baccetti, Tiziano; Franchi, Lorenzo; De Lisa, Simona; Giuntini, Veronica

    2008-05-01

    Our aim in this study was to assess the relationship between the eruption of the permanent maxillary canines and skeletal maturity in subjects with different skeletal relationships in the sagittal and vertical planes. A sample of 152 subjects (63 boys, 89 girls) with erupting permanent maxillary canines was analyzed. On the lateral cephalograms, the stage of cervical vertebral maturation was assessed. Then the subjects were divided into prepeak (before the pubertal growth spurt, cervical stage [CS]1 and CS2), peak (during the pubertal growth spurt, CS3 and CS4), and postpeak (after the pubertal growth spurt, CS5 and CS6) groups. Skeletal relationships in the sagittal and vertical planes were evaluated, and relationships to timing of canine eruption were tested statistically. The prepeak group comprised 86 subjects, the peak group 66 subjects, and the postpeak group 0 subjects. The differences in prevalence rates between either the prepeak or peak groups and the postpeak group were statistically significant (P < 0.001). The prevalence rate for hyperdivergent subjects showing eruption of the permanent maxillary canine in the prepeak group (37.2%) was significantly higher than in the reference orthodontic population (21%). The eruption of the permanent maxillary canine can occur at any stage in skeletal maturation before the end the pubertal growth spurt (CS1-CS4), with hyperdivergent subjects more frequently having prepubertal canine eruption.

  9. Dental and Skeletal Maturity- A Biological Indicator of Chronologic Age

    Science.gov (United States)

    Saha, Sonali; Yadav, Gunjan; Tripathi, Abhay Mani; Grover, Kavita

    2014-01-01

    Introduction: Precise evaluation of the developmental stage of a child is not only an integral part of both diagnosis and treatment of paediatric patients; it is also essential in Forensic Medicine and Dentistry. Physiologic age can be estimated by somatic, sexual, skeletal and dental maturity. Aim: Investigate the relationship between the dental age (DA) and skeletal age (SA) of children and comparing it with the chronological age (CA). Materials and Methods: The dental age estimation methods of Schour and Massler (S&M), and Demirjian and Goldstien (D&G) and skeletal assessment methods of Greulich and Pyle (G&P), and Tanner et al., (TW2) were used to analyze the orthopantomograms and hand-wrist radiographs respectively of 150 healthy subjects within the age range of 5-15 y and compared with the Chronological Age. Statistical Analysis: Data collected was statistically analysed using the SPSS version 15.0 Statistical Analysis Software. For all tests p-value of <0.05 were considered statistically significance. Results: Dental age estimation techniques were found comparable and equally reliable as the skeletal age estimation methods. Strong correlations between dental and skeletal maturation were demonstrated. PMID:25386525

  10. Correlation between chronological age, cervical vertebral maturation and Fishman's skeletal maturity indicators in southern Chinese.

    Science.gov (United States)

    Alkhal, Hessa Abdulla; Wong, Ricky W K; Rabie, A Bakr M

    2008-07-01

    To investigate the correlation between chronological age, cervical vertebral maturation (CVM), and Fishman's hand-wrist skeletal maturity indicators in southern Chinese. Four hundred contemporary hand-wrist and lateral cephalometric radiographs of southern Chinese subjects were randomly selected and analyzed. The female subjects were between 10 and 15 years of age, and the male subjects were between 12 and 17 years of age; all subjects were within the circumpubertal period. The CVM was assessed using the method developed by Baccetti and coworkers, but the hand-wrist maturation was assessed using the method developed by Fishman. These two methods and the chronological age were correlated using the Spearman rank correlation analysis. The CVM was significantly correlated with the hand-wrist skeletal age (Spearman r male = 0.9206, female = 0.9363). All patients in the cervical maturation stage (CS3) of CVM were discovered to be in the skeletal maturational indicator (SMI2 or SMI3) stages of hand-wrist maturation (HWM), which was around the peak of the growth spurt. Low correlations were found between the CVM and chronological age (male r = 0.7577; female r = 0.7877) and between the HWM and chronological age (male r = 0.7492; female r = 0.7758). CVM is a valid indicator of skeletal growth during the circumpubertal and has a high correlation with the HWM for the southern Chinese population. However, the low correlations found between the chronological age and both CVM and HWM showed that the chronological age was not suitable to measure skeletal maturity.

  11. ASSOCIATION BETWEEN DENTAL AND SKELETAL MATURATION STAGES IN CROATIAN SUBJECTS.

    Science.gov (United States)

    Srkoc, Tamara; Mestrović, Senka; Anić-Milosević, Sandra; Slaj, Mladen

    2015-12-01

    This study investigated the relationships between the stages of calcification of teeth and cervical vertebral maturation. The sample consisted of 295 subjects (129 male and 166 female), mean age 13.36 ± 2.65 (range 7-18) years. Dental age was evaluated from panoramic radiographs according to the method of Demirjian. Cervical vertebral maturation was determined on lateral cephalometric radiographs using cervical vertebrae maturation stages (CVS). For assessing the relationship between cervical vertebral and dental maturation, percentage distributions of the stages of calcification for each studied tooth were calculated. Only in the first CVS stage, boys and girls were of the same age. In all other stages (CVS 2-CVS 6) girls were by 0.98 (range 0.23-1.86) younger than boys. Gender differences in the mineralization pattern were also observed. It was found that dental maturation was finished earlier in female subjects. The highest correlation coefficient between dental and skeletal maturity was found for second premolars. Mineralization pattern of second premolars could be considered as a guideline for prediction of the pubertal growth spurt. Dental maturation stages might be clinically useful as a reliable indicator of facial growth.

  12. Assessment of skeletal maturation based on cervical vertebrae in CBCT.

    Science.gov (United States)

    Shim, Jocelyne J; Heo, Giseon; Lagravère, Manuel O

    2012-12-01

    Diagnosis of skeletal age in adolescents helps orthodontists select and time treatments. Currently this is done using lateral cephalometric radiographs. This study evaluates the application of the conventional method in cone-beam computer tomographic (CBCT) images to bring forth assessment of skeletal maturation in three-dimensions. Ninety-eight lateral cephalometric radiographs and CBCT scans were collected from orthodontic patients between 11 to 17 years of age over an 18-month period. CBCT scans were examined in seven sagittal slices based on cervical vertebral maturation staging (CVMS). Collected CVMS values were compared with those from corresponding lateral cephalometric radiograph. CVMS measured from CBCT and lateral cephalometric radiographs were the same on average. However, they were not consistent with each other and scored interclass correlation coefficient of 0.155 in validity test. Interoperator reliability was weak (0.581). Adaptation of cervical vertebrae maturation staging in CBCT requires further clarifications or modifications to become consistent with lateral cephalometric examinations and to become a reliable method. Alternatively, a completely new method may be developed consisting of maturational indicators or landmarks unique to CBCT imaging. Copyright © 2012. Published by Elsevier Masson SAS.

  13. Growth indicators in orthodontic patients. Part 1: comparison of cervical vertebral maturation and hand-wrist skeletal maturation.

    Science.gov (United States)

    Litsas, G; Ari-Demirkaya, A

    2010-12-01

    The purpose of this study was to predict the skeletal maturation status based on the assessment of cervical vertebrae from lateral cephalometric radiographs and to compare these findings with the skeletal maturity of the same individuals judged from the hand-wrist radiographs. Lateral cephalometric and left hand-wrist radiographs of 393 Caucasian children from 8 to 18 years old were evaluated. On the hand-wrist radiographs the classification of Bjork [1972] and Grave and Brown [1976] was used to assess skeletal maturity (HWSS). Cervical vertebral maturation was also evaluated on lateral cephalometric radiographs using the improved CVMS method described by Baccetti, Franchi, and McNamara [2002]. These methods were correlated using the chi-square test. The chi-square test showed that skeletal maturational values obtained by the CVMS method were significantly correlated with the skeletal values obtained from the hand-wrist analysis for both genders (pmaturity.

  14. Comparison of three methods to assess individual skeletal maturity.

    Science.gov (United States)

    Pasciuti, Enzo; Franchi, Lorenzo; Baccetti, Tiziano; Milani, Silvano; Farronato, Giampietro

    2013-09-01

    The knowledge of facial growth and development is fundamental to determine the optimal timing for different treatment procedures in the growing patient. To analyze the reproducibility of three methods in assessing individual skeletal maturity, and to evaluate any degree of concordance among them. In all, 100 growing subjects were enrolled to test three methods: the hand-wrist, cervical vertebral maturation (CVM), and medial phalanges of the third finger method (MP3). Four operators determined the skeletal maturity of the subjects to evaluate the reproducibility of each method. After 30 days the operators repeated the analysis to assess the repeatability of each method. Finally, one operator examined all subjects' radiographs to detect any concordance among the three methods. The weighted kappa values for inter-operator variability were 0.94, 0.91, and 0.90, for the WRI, CVM, and MP3 methods, respectively. The weighted kappa values for intra-operator variability were 0.92, 0.91, and 0.92, for the WRI, CVM, and MP3 methods, respectively. The three methods revealed a high degree of repeatability and reproducibility. Complete agreement among the three methods was observed in 70% of the analyzed samples. The CVM method has the advantage of not necessitating an additional radiograph. The MP3 method is a simple and practical alternative as it requires only a standard dental x-ray device.

  15. Nuclear magnetic resonance studies on maturation of skeletal muscle

    International Nuclear Information System (INIS)

    Yuasa, Tatsuhiko; Kuwahara, Takeo; Ohno, Takao; Miyatake, Tadashi.

    1982-01-01

    The water proton relaxation time ( 1 H-T 1 ) of the maturing chick pectoral muscle and the 23 Na concentration in the muscular tissue were determined by NMR spectrometry. 1 H-T 1 was determined on 12-day-old chick embryos, 19- and 20-day-old embryos and chicks aged 8, 15 and 22 days. 23 Na concentration was determined on 12-14 day-old chick embryos, 19-day-old embryos and 4-6 day-old and 20-day-old chicks. 1 H-T 1 gradually decreased with maturation; 2.082 +- 0.091 sec, 1.605 +- 0.106 sec, 1.321 +- 0.107 sec, 1.108 +- 0.038 sec and 1.087 +- 0.053 sec. The 23 Na level showed similar decreases; 59.5 +- 3.51 μEq/gm, 49.0 +- 4.95 μEq/gm, 47.5 +- 3.87 μEq/gm and 10.3 +- 2.13 μEq/gm. The water content in the skeletal muscle decreased with maturation, and 1 H-T 1 and the water content showed an exponential relationship. Comparison between the 23 Na concentration of muscle tissues determined by NMR and the Na + concentration by flame photometry revealed a decrease of the detection rate of 23 Na by NMR from 81.9 % to 54.7 % with maturation. It was conjectured that as well as the mode of existence of water proton, that of 23 Na in the tissue was subject to changes occurring with maturation of the skeletal muscle. (Chiba, N.)

  16. Cervical Vertebral Body's Volume as a New Parameter for Predicting the Skeletal Maturation Stages

    OpenAIRE

    Choi, Youn-Kyung; Kim, Jinmi; Yamaguchi, Tetsutaro; Maki, Koutaro; Ko, Ching-Chang; Kim, Yong-Il

    2016-01-01

    This study aimed to determine the correlation between the volumetric parameters derived from the images of the second, third, and fourth cervical vertebrae by using cone beam computed tomography with skeletal maturation stages and to propose a new formula for predicting skeletal maturation by using regression analysis. We obtained the estimation of skeletal maturation levels from hand-wrist radiographs and volume parameters derived from the second, third, and fourth cervical vertebrae bodies ...

  17. Effects of posttreatment skeletal maturity measured with the cervical vertebral maturation method on incisor alignment relapse.

    Science.gov (United States)

    Fudalej, Piotr; Rothe, Laura E; Bollen, Anne-Marie

    2008-08-01

    Our aim was to test the hypothesis that relapse of incisor alignment is associated with skeletal maturity at the end of treatment, as assessed with the cervical vertebral maturation (CVM) method. This was a case-control study with information from the postretention database at the University of Washington. Mandibular incisor irregularity (II) at least 10 years out of retention (T3) was used to define the subjects (II >6 mm, relapse group) and the controls (II 0.05). Pretreatment II and postretention time were found to be correlated with long-term incisor stability (P = 0.007 and 0.034, respectively). Sex was not related to relapse (P = 0.33). Maturity of craniofacial structures at the end of treatment evaluated with the CVM method is not associated with long-term stability of incisor alignment.

  18. Diagnostic assessment of skeletal maturity through dental maturation in Hispanic growing individuals

    Directory of Open Access Journals (Sweden)

    Alejandra Cisternas

    2017-01-01

    Full Text Available Background: The aim of this study was to explore dental maturation as a diagnostic test for skeletal maturation. Materials and Methods: Six hundred and fifty-seven growing individuals were classified according to their cervical vertebral maturity and dental maturity, both determined in lateral cephalograms and panoramic radiographs, respectively. The correlation between cervical and dental stages was established for each gender. A receiver operating characteristic curve analysis was made, and sensitivity and specificity values were established. Results: Correlation was found between cervical and dental maturation for females (r = 0.73; P<0.001 and males (r = 0.60; P<0.001. Sensitivity for dental Stage F, as an indicator of a postmaturation peak stage, was 87.21% for females and 97.1% for males, whereas specificity for the same stage was 82.92% and 72.3% for females and males, respectively. Conclusions: Dental maturation evaluation could contribute determining whether a patient is in a pre- or post-growth spurt stage.

  19. Impact of ensemble learning in the assessment of skeletal maturity.

    Science.gov (United States)

    Cunha, Pedro; Moura, Daniel C; Guevara López, Miguel Angel; Guerra, Conceição; Pinto, Daniela; Ramos, Isabel

    2014-09-01

    The assessment of the bone age, or skeletal maturity, is an important task in pediatrics that measures the degree of maturation of children's bones. Nowadays, there is no standard clinical procedure for assessing bone age and the most widely used approaches are the Greulich and Pyle and the Tanner and Whitehouse methods. Computer methods have been proposed to automatize the process; however, there is a lack of exploration about how to combine the features of the different parts of the hand, and how to take advantage of ensemble techniques for this purpose. This paper presents a study where the use of ensemble techniques for improving bone age assessment is evaluated. A new computer method was developed that extracts descriptors for each joint of each finger, which are then combined using different ensemble schemes for obtaining a final bone age value. Three popular ensemble schemes are explored in this study: bagging, stacking and voting. Best results were achieved by bagging with a rule-based regression (M5P), scoring a mean absolute error of 10.16 months. Results show that ensemble techniques improve the prediction performance of most of the evaluated regression algorithms, always achieving best or comparable to best results. Therefore, the success of the ensemble methods allow us to conclude that their use may improve computer-based bone age assessment, offering a scalable option for utilizing multiple regions of interest and combining their output.

  20. Association between frontal sinus morphology and cervical vertebral maturation for the assessment of skeletal maturity.

    Science.gov (United States)

    Mahmood, Hafiz Taha; Shaikh, Attiya; Fida, Mubassar

    2016-10-01

    Various methods have been proposed to evaluate a patient's developmental status. However, most of them lacked precision and failed to give a reliable estimate of skeletal maturity. The aims of this study were to evaluate the association between frontal sinus morphology and cervical vertebral maturation for the assessment of skeletal maturity and to determine its validity in assessing the different stages of the adolescent growth spurt. A cross-sectional study was performed on the pretreatment lateral cephalograms of 252 subjects aged 8 to 21 years. The sample was divided into 6 groups based on the cervical vertebral maturation stages. The frontal sinus index was calculated by dividing the frontal sinus height and width, and the cervical stages were evaluated on the same radiograph. The Kruskal-Wallis test was applied to compare frontal sinus index values at different cervical stages, and the post hoc Dunnett T3 test was applied to compare frontal sinus index values between adjacent cervical stages for each sex. The Kendall tau-b values were computed to assess the correlation between the cervical stages and the sinus index. A P value of ≤0.05 was considered statistically significant. The height and width of the frontal sinus were significantly larger in the male subjects than in the females. A significant association was found between the frontal sinus height and width and cervical stages (P ≤0.001) in both sexes. However, the changes in the frontal sinus index across the different cervical stages were found to be significant (P ≤0.001) in male subjects only. Similarly, a weak negative correlation was found between the sinus index and the cervical stages in male subjects (tau-b = -0.271; P cervical stages. The frontal sinus index cannot be used to identify the prepubertal, pubertal, and postpubertal stages of the adolescent growth spurt. Therefore, it cannot be used as a reliable maturity indicator. Copyright © 2016 American Association of

  1. The diagnostic performance of chronologic age in the assessment of skeletal maturity.

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    Baccetti, Tiziano; Franchi, Lorenzo; De Toffol, Laura; Ghiozzi, Bruno; Cozza, Paola

    2006-01-01

    The aim of this study was to analyze the relationship between chronologic age the and individual skeletal maturity as assessed by means of the cervical vertebral maturation (CVM) method during the circumpubertal period. The evaluated sample of 600 subjects consisted of 100 subjects (50 males and 50 females) for each of 6 age groups, from 9 years through 14 years of age. Individual skeletal maturity for all subjects was determined by using the CVM method. The relationship between chronologic age and the most prevalent CVM stage at each age group was evaluated statistically by means of indicators of diagnostic test performance that specify the ability of a diagnostic test to identify a condition. The diagnostic performance of chronologic age for the detection of the onset of the adolescent peak in skeletal maturation was very low both in males and in females. In male subjects, the chronologic age of 9 years +/- 6 months presented with strong diagnostic power for the identification of a pre-pubertal stage in skeletal maturation. In female subjects, the chronologic age of 14 years +/- 6 months corresponded with a strong probability of a postpubertal stage in skeletal maturation. In males, chronologic age can identify a pre-pubertal stage of skeletal development, and in females a post-pubertal stage. In both males and females, chronologic age cannot recognize the onset of the adolescent peak in skeletal maturation.

  2. Characterising the proximal patellar tendon attachment and its relationship to skeletal maturity in adolescent ballet dancers

    DEFF Research Database (Denmark)

    Rudavsky, Aliza; Cook, Jillianne; Magnusson, Stig Peter

    2017-01-01

    gain an understanding of how and when the tendon attachment matures. Methods: Sixty adolescent elite ballet students (ages 11-18) and eight mature adults participated. Peak height velocity (PHV) estimated skeletal maturity. Ultrasound tissue characterisation (UTC) scan was taken of the left knee...

  3. Relative Skeletal Maturation and Population Ancestry in Nonobese Children and Adolescents.

    Science.gov (United States)

    McCormack, Shana E; Chesi, Alessandra; Mitchell, Jonathan A; Roy, Sani M; Cousminer, Diana L; Kalkwarf, Heidi J; Lappe, Joan M; Gilsanz, Vicente; Oberfield, Sharon E; Shepherd, John A; Mahboubi, Soroosh; Winer, Karen K; Kelly, Andrea; Grant, Struan Fa; Zemel, Babette S

    2017-01-01

    More rapid skeletal maturation in African-American (AA) children is recognized and generally attributed to an increased prevalence of obesity. The objective of the present study was to evaluate the effects of population ancestry on relative skeletal maturation in healthy, non-obese children and adolescents, accounting for body composition and sexual maturation. To do this, we leveraged a multiethnic, mixed-longitudinal study with annual assessments for up to 7 years (The Bone Mineral Density in Childhood Study and its ancillary cohort) conducted at five US clinical centers. Participants included 1592 children, skeletally immature (45% females, 19% AA) who were aged 5 to 17 years at study entry. The primary outcome measure was relative skeletal maturation as assessed by hand-wrist radiograph. Additional covariates measured included anthropometrics, body composition by dual-energy X-ray absorptiometry (DXA), and Tanner stage of sexual maturation. Using mixed effects longitudinal models, without covariates, advancement in relative skeletal maturation was noted in self-reported AA girls (∼0.33 years, p ancestry groups showed independent positive associations of height, lean mass, fat mass, and puberty with relative skeletal maturation. The effect of ancestry was attenuated but persistent after accounting for covariates: for girls, 0.19 years (ancestry by self-report, p = 0.02) or 0.29 years (ancestry by admixture, p = 0.004); and for boys, 0.20 years (ancestry by self-report, p = 0.004), or 0.29 years (ancestry by admixture, p = 0.004). In summary, we conclude that advancement in relative skeletal maturation was associated with AA ancestry in healthy, non-obese children, independent of growth, body composition, and puberty. Further research into the mechanisms underlying this observation may provide insights into the regulation of skeletal maturation. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and

  4. Comparative study between the hand-wrist method and cervical vertebral maturation method for evaluation skeletal maturity in cleft patients.

    Science.gov (United States)

    Manosudprasit, Montian; Wangsrimongkol, Tasanee; Pisek, Poonsak; Chantaramungkorn, Melissa

    2013-09-01

    To test the measure of agreement between use of the Skeletal Maturation Index (SMI) method of Fishman using hand-wrist radiographs and the Cervical Vertebral Maturation Index (CVMI) method for assessing skeletal maturity of the cleft patients. Hand-wrist and lateral cephalometric radiographs of 60 cleft subjects (35 females and 25 males, age range: 7-16 years) were used. Skeletal age was assessed using an adjustment to the SMI method of Fishman to compare with the CVMI method of Hassel and Farman. Agreement between skeletal age assessed by both methods and the intra- and inter-examiner reliability of both methods were tested by weighted kappa analysis. There was good agreement between the two methods with a kappa value of 0.80 (95% CI = 0.66-0.88, p-value <0.001). Reliability of intra- and inter-examiner of both methods was very good with kappa value ranging from 0.91 to 0.99. The CVMI method can be used as an alternative to the SMI method in skeletal age assessment in cleft patients with the benefit of no need of an additional radiograph and avoiding extra-radiation exposure. Comparing the two methods, the present study found better agreement from peak of adolescence onwards.

  5. The skeletal maturation status estimated by statistical shape analysis: axial images of Japanese cervical vertebra.

    Science.gov (United States)

    Shin, S M; Kim, Y-I; Choi, Y-S; Yamaguchi, T; Maki, K; Cho, B-H; Park, S-B

    2015-01-01

    To evaluate axial cervical vertebral (ACV) shape quantitatively and to build a prediction model for skeletal maturation level using statistical shape analysis for Japanese individuals. The sample included 24 female and 19 male patients with hand-wrist radiographs and CBCT images. Through generalized Procrustes analysis and principal components (PCs) analysis, the meaningful PCs were extracted from each ACV shape and analysed for the estimation regression model. Each ACV shape had meaningful PCs, except for the second axial cervical vertebra. Based on these models, the smallest prediction intervals (PIs) were from the combination of the shape space PCs, age and gender. Overall, the PIs of the male group were smaller than those of the female group. There was no significant correlation between centroid size as a size factor and skeletal maturation level. Our findings suggest that the ACV maturation method, which was applied by statistical shape analysis, could confirm information about skeletal maturation in Japanese individuals as an available quantifier of skeletal maturation and could be as useful a quantitative method as the skeletal maturation index.

  6. Relationship Between Age at Menarche and Skeletal Maturation Stages in Taiwanese Female Orthodontic Patients

    OpenAIRE

    Lai, Eddie Hsiang-Hua; Chang, Jenny Zwei-Chieng; Yao, Chung-Chen Jane; Tsai, Shih-Jaw; Liu, Jen-Pei; Chen, Yi-Jane; Lin, Chun-Pin

    2008-01-01

    Background/Purpose: The age at menarche reflects a pubertal girl's physiologic maturity. The aims of this study were to evaluate the relationship between the age at menarche and skeletal maturation in female orthodontic patients. Methods: Hand-wrist radiographs and lateral cephalometric radiographs from 304 adolescent female subjects (age, 8–18.9 years) were selected from the files of the Department of Orthodontics, National Taiwan University Hospital (NTUH). Hand-wrist bone maturation sta...

  7. Radiographic assessment of skeletal maturation stages for orthodontic patients: hand-wrist bones or cervical vertebrae?

    Science.gov (United States)

    Lai, Eddie Hsiang-Hua; Liu, Jen-Pei; Chang, Jenny Zwei-Chieng; Tsai, Shih-Jaw; Yao, Chung-Chen Jane; Chen, Mu-Hsiung; Chen, Yi-Jane; Lin, Chun-Pin

    2008-04-01

    The skeletal maturation status of a growing patient can influence the selection of orthodontic treatment procedures. Either lateral cephalometric or hand-wrist radiography can be used to assess skeletal development. In this study, we examined the correlation between the maturation stages of cervical vertebrae and hand-wrist bones in Taiwanese individuals. The study group consisted of 330 male and 379 female subjects ranging in age from 8 to 18 years. A total of 709 hand-wrist and 709 lateral cephalometric radiographs were analyzed. Hand-wrist maturation stages were assessed using National Taiwan University Hospital Skeletal Maturation Index (NTUH-SMI). Cervical vertebral maturation stages were determined by the latest Cervical Vertebral Maturation Stage (CVMS) Index. Spearman's rank correlation was used to correlate the respective maturation stages assessed from the hand-wrist bones and the cervical vertebrae. The values of Spearman's rank correlation were 0.910 for males and 0.937 for females, respectively. These data confirmed a strong and significant correlation between CVMS and NTUH-SMI systems (p less than 0.001). After comparison of the mean ages of subjects in different stages of CVMS and NTU-SMI systems, we found that CVMS I corresponded to NTUH-SMI stages 1 and 2, CVMS II to NTUH-SMI stage 3, CVMS III to NTUHSMI stage 4, CVMS IV to NTUH-SMI stage 5, CVMS V to NTUH-SMI stages 6, 7 and 8, and CVMS VI to NTUH-SMI stage 9. Our results indicate that cervical vertebral maturation stages can be used to replace hand-wrist bone maturation stages for evaluation of skeletal maturity in Taiwanese individuals.

  8. Geometric morphometric evaluation of cervical vertebrae shape and its relationship to skeletal maturation.

    Science.gov (United States)

    Chatzigianni, Athina; Halazonetis, Demetrios J

    2009-10-01

    Cervical vertebrae shape has been proposed as a diagnostic factor for assessing skeletal maturation in orthodontic patients. However, evaluation of vertebral shape is mainly based on qualitative criteria. Comprehensive quantitative measurements of shape and assessments of its predictive power have not been reported. Our aims were to measure vertebral shape by using the tools of geometric morphometrics and to evaluate the correlation and predictive power of vertebral shape on skeletal maturation. Pretreatment lateral cephalograms and corresponding hand-wrist radiographs of 98 patients (40 boys, 58 girls; ages, 8.1-17.7 years) were used. Skeletal age was estimated from the hand-wrist radiographs. The first 4 vertebrae were traced, and 187 landmarks (34 fixed and 153 sliding semilandmarks) were used. Sliding semilandmarks were adjusted to minimize bending energy against the average of the sample. Principal components analysis in shape and form spaces was used for evaluating shape patterns. Shape measures, alone and combined with centroid size and age, were assessed as predictors of skeletal maturation. Shape alone could not predict skeletal maturation better than chronologic age. The best prediction was achieved with the combination of form space principal components and age, giving 90% prediction intervals of approximately 200 maturation units in the girls and 300 units in the boys. Similar predictive power could be obtained by using centroid size and age. Vertebrae C2, C3, and C4 gave similar results when examined individually or combined. C1 showed lower correlations, signifying lower integration with hand-wrist maturation. Vertebral shape is strongly correlated to skeletal age but does not offer better predictive value than chronologic age.

  9. Dentofacial transverse development in Koreans according to skeletal maturation: A cross-sectional study.

    Science.gov (United States)

    Hwang, Soonshin; Noh, Yoonjeong; Choi, Yoon Jeong; Chung, Chooryung; Lee, Hye Sun; Kim, Kyung-Ho

    2018-01-01

    The aim of this study was to establish the normative data of dentofacial transverse dimensions according to the skeletal maturation stage in Korean adolescents with good occlusion, assess gender differences and determine correlations between transverse variables. A total of 577 Korean subjects between ages 7 to 19 years and exhibiting skeletal Class I occlusion were categorized by skeletal maturation index (SMI) of Fishman using hand-wrist radiographs. Dentofacial transverse dimensions were assessed using posteroanterior cephalograms. Independent two-sample t -tests were used to analyze differences between genders. Pearson correlation coefficient was used to determine the correlation between transverse measurements. Dentofacial transverse norms relevant to skeletal maturation stages were established. The average maxillomandibular width difference and ratio at growth completion was 22.16 mm and 77.01% for males; 23.70 mm and 74.06% for females, respectively. Males had greater facial, maxillary and mandibular widths compared to females at every SMI stage. The maxillary and mandibular intermolar widths showed the strongest correlation for both sexes (r = 0.826 for males, r = 0.725 for females). Dentofacial transverse norms of Korean adolescents were established according to developmental stage. All dentofacial widths were greater in males at growth completion. Maxillary and mandibular intermolar widths were strongly correlated. This study may serve as a guideline for the assessment of dentofacial transverse growth according to skeletal maturation stage in Korean adolescents with good occlusion.

  10. Quantitative skeletal evaluation based on cervical vertebral maturation: a longitudinal study of adolescents with normal occlusion.

    Science.gov (United States)

    Chen, L; Liu, J; Xu, T; Long, X; Lin, J

    2010-07-01

    The study aims were to investigate the correlation between vertebral shape and hand-wrist maturation and to select characteristic parameters of C2-C5 (the second to fifth cervical vertebrae) for cervical vertebral maturation determination by mixed longitudinal data. 87 adolescents (32 males, 55 females) aged 8-18 years with normal occlusion were studied. Sequential lateral cephalograms and hand-wrist radiographs were taken annually for 6 consecutive years. Lateral cephalograms were divided into 11 maturation groups according to Fishman Skeletal Maturity Indicators (SMI). 62 morphological measurements of C2-C5 at 11 different developmental stages (SMI1-11) were measured and analysed. Locally weighted scatterplot smoothing, correlation coefficient analysis and variable cluster analysis were used for statistical analysis. Of the 62 cervical vertebral parameters, 44 were positively correlated with SMI, 6 were negatively correlated and 12 were not correlated. The correlation coefficients between cervical vertebral parameters and SMI were relatively high. Characteristic parameters for quantitative analysis of cervical vertebral maturation were selected. In summary, cervical vertebral maturation could be used reliably to evaluate the skeletal stage instead of the hand-wrist radiographic method. Selected characteristic parameters offered a simple and objective reference for the assessment of skeletal maturity and timing of orthognathic surgery. Copyright 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  11. A new method for assessment of skeletal maturity in the first 2 years of life

    International Nuclear Information System (INIS)

    Hernandez, M.; Sanchez, E.; Sobradillo, B.; Rincon, J.M.; Narvaiza, J.L.

    1988-01-01

    We present an original scoring method for assessing skeletal maturity in the first 2 years of life. We propose a lateral radiograph of the ankle and foot. Five different bony centers were examined: The calcaneus, the cuboid, the third cuneiform, the distal tibial epiphysis and the distal fibular epiphysis. The maturity scores given to the different stages of each bony center were calculated in proportion to the coefficients of regression between the skeletal maturity and a factor that expresses the influence of weight and head circumference as high multiple correlation coefficients of skeletal maturity with the factor obtained (0.920 for boys ad 0.929 for girls). Our method was standardized in a children population of less than two years of life in Biscaye, where 1,164 radiographs were taken. The distribution of scores in this study shows the discriminative ability of our method and its validity as an adequate method for skeletal maturity assessment in children less than 2 years of age. (orig.)

  12. Skeletal maturation, fundamental motor skills and motor coordination in children 7-10 years.

    Science.gov (United States)

    Freitas, Duarte L; Lausen, Berthold; Maia, José António; Lefevre, Johan; Gouveia, Élvio Rúbio; Thomis, Martine; Antunes, António Manuel; Claessens, Albrecht L; Beunen, Gaston; Malina, Robert M

    2015-01-01

    Relationships between skeletal maturation and fundamental motor skills and gross motor coordination were evaluated in 429 children (213 boys and 216 girls) 7-10 years. Skeletal age was assessed (Tanner-Whitehouse 2 method), and stature, body mass, motor coordination (Körperkoordinations Test für Kinder, KTK) and fundamental motor skills (Test of Gross Motor Development, TGMD-2) were measured. Relationships among chronological age, skeletal age (expressed as the standardised residual of skeletal age on chronological age) and body size and fundamental motor skills and motor coordination were analysed with hierarchical multiple regression. Standardised residual of skeletal age on chronological age interacting with stature and body mass explained a maximum of 7.0% of the variance in fundamental motor skills and motor coordination over that attributed to body size per se. Standardised residual of skeletal age on chronological age alone accounted for a maximum of 9.0% of variance in fundamental motor skills, and motor coordination over that attributed to body size per se and interactions between standardised residual of skeletal age on chronological age and body size. In conclusion, skeletal age alone or interacting with body size has a negligible influence on fundamental motor skills and motor coordination in children 7-10 years.

  13. Cervical Vertebral Body’s Volume as a New Parameter for Predicting the Skeletal Maturation Stages

    Directory of Open Access Journals (Sweden)

    Youn-Kyung Choi

    2016-01-01

    Full Text Available This study aimed to determine the correlation between the volumetric parameters derived from the images of the second, third, and fourth cervical vertebrae by using cone beam computed tomography with skeletal maturation stages and to propose a new formula for predicting skeletal maturation by using regression analysis. We obtained the estimation of skeletal maturation levels from hand-wrist radiographs and volume parameters derived from the second, third, and fourth cervical vertebrae bodies from 102 Japanese patients (54 women and 48 men, 5–18 years of age. We performed Pearson’s correlation coefficient analysis and simple regression analysis. All volume parameters derived from the second, third, and fourth cervical vertebrae exhibited statistically significant correlations (P<0.05. The simple regression model with the greatest R-square indicated the fourth-cervical-vertebra volume as an independent variable with a variance inflation factor less than ten. The explanation power was 81.76%. Volumetric parameters of cervical vertebrae using cone beam computed tomography are useful in regression models. The derived regression model has the potential for clinical application as it enables a simple and quantitative analysis to evaluate skeletal maturation level.

  14. Cervical Vertebral Body's Volume as a New Parameter for Predicting the Skeletal Maturation Stages.

    Science.gov (United States)

    Choi, Youn-Kyung; Kim, Jinmi; Yamaguchi, Tetsutaro; Maki, Koutaro; Ko, Ching-Chang; Kim, Yong-Il

    2016-01-01

    This study aimed to determine the correlation between the volumetric parameters derived from the images of the second, third, and fourth cervical vertebrae by using cone beam computed tomography with skeletal maturation stages and to propose a new formula for predicting skeletal maturation by using regression analysis. We obtained the estimation of skeletal maturation levels from hand-wrist radiographs and volume parameters derived from the second, third, and fourth cervical vertebrae bodies from 102 Japanese patients (54 women and 48 men, 5-18 years of age). We performed Pearson's correlation coefficient analysis and simple regression analysis. All volume parameters derived from the second, third, and fourth cervical vertebrae exhibited statistically significant correlations (P cervical-vertebra volume as an independent variable with a variance inflation factor less than ten. The explanation power was 81.76%. Volumetric parameters of cervical vertebrae using cone beam computed tomography are useful in regression models. The derived regression model has the potential for clinical application as it enables a simple and quantitative analysis to evaluate skeletal maturation level.

  15. Relationship between age at menarche and skeletal maturation stages in Taiwanese female orthodontic patients.

    Science.gov (United States)

    Lai, Eddie Hsiang-Hua; Chang, Jenny Zwei-Chieng; Jane Yao, Chung-Chen; Tsai, Shih-Jaw; Liu, Jen-Pei; Chen, Yi-Jane; Lin, Chun-Pin

    2008-07-01

    The age at menarche reflects a pubertal girl's physiologic maturity. The aims of this study were to evaluate the relationship between the age at menarche and skeletal maturation in female orthodontic patients. Hand-wrist radiographs and lateral cephalometric radiographs from 304 adolescent female subjects (age, 8-18.9 years) were selected from the files of the Department of Orthodontics, National Taiwan University Hospital (NTUH). Hand-wrist bone maturation stages were assessed using the NTUH Skeletal Maturation Index (NTUH-SMI). Cervical vertebral maturation stages (CVMS) were determined using the latest CVMS Index. Menarcheal ages were self-reported by the patients and verified by the patients' mothers. The relationships between the NTUH-SMI or CVM stages and menarcheal status were investigated. More than 90% of the 148 subjects who had already attained menstruation had skeletal maturation beyond the NTUH-SMI stage four or CVMS III. However, the subjects who had never experienced menarche mostly had skeletal maturation before NTUH-SMI stage five or CVMS IV. During the period of orthodontic treatment, 19 females experienced their menarche. The mean age at menarche for the 167 female patients in total was 11.97 years. In average, menarche occurred between NTUH-SMI stages four and five or between CVM stages III and IV. The percentage of girls with menses increased from 1.2% at age 9 to 6.6% at age 10, 39.5% at age 11, 81.4% at age 12, 97% at age 13, and 100% at age 14. Compared with the results obtained 20 years previously, we found a downward shift of 0.47 years per decade for the mean age at menarche in female orthodontic patients. The majority of female orthodontic patients have passed the pubertal growth spurt when they experience their menarche. Menarche usually follows the pubertal growth spurt by about 1 year and occurs after NTUH-SMI stage four or CVMS III.

  16. A Comparison of Hand Wrist Bone Analysis with Two Different Cervical Vertebral Analysis in Measuring Skeletal Maturation

    OpenAIRE

    Pichai, Saravanan; Rajesh, M; Reddy, Naveen; Adusumilli, Gopinath; Reddy, Jayaprakash; Joshi, Bhavana

    2014-01-01

    Background: Skeletal maturation is an integral part of individual pattern of growth and development and is a continuous process. Peak growth velocity in standing height is the most valid representation of the rate of overall skeletal growth. Ossification changes of hand wrist and cervical vertebrae are the reliable indicators of growth status of individual. The objective of this study was to compare skeletal maturation as measured by hand wrist bone analysis and cervical vertebral analysis. M...

  17. A comparison of skeletal maturation in patients with tooth agenesis and unaffected controls assessed by the cervical vertebral maturation (CVM) index.

    Science.gov (United States)

    Casey, Christine; Gill, Daljit S; Jones, Steven P

    2013-12-01

    The aims of this study were to (1) investigate if there is a difference in skeletal maturation between tooth agenesis and control patients and (2) whether skeletal maturation is affected by the severity of tooth agenesis. The cervical vertebral maturation (CVM) index can be used to assess skeletal maturation. A retrospective cross-sectional study. Eastman Dental Hospital, London, UK. A total of 360 cephalograms of patients aged 9-17 years (164 males and 196 females) allocated to four subgroups (mild, moderate and severe tooth agenesis patients, and controls) were assessed retrospectively. There were 90 patients in each of the four subgroups. The skeletal maturation of each subject was assessed both quantitatively and qualitatively using the CVM index. All patients in the study were either currently receiving treatment or had been discharged from the hospital. There was no statistically significant relationship between skeletal maturation and the presence of tooth agenesis. Furthermore, there was no statistically significant relationship between the skeletal maturity of patients and different severities of tooth agenesis. The data obtained from this group of patients and using this measurement tool alone does not supply sufficient reason to reject the null hypothesis. However, it suggests that it is possible that no difference exists between the groups.

  18. [Study on the difference of corresponding age at cervical vertebral maturation stages among different skeletal malocclusions].

    Science.gov (United States)

    Zuo, Changyan; Cong, Chao; Wang, Shihui; Gu, Yan

    2015-10-01

    To compare the difference of corresponding age at cervical vertebral maturation (CVM) stages among different skeletal malocclusions and provide clinic guideline on optimal treatment timing for skeletal malocclusion. Based on ANB angle, 2 575 cephalograms collected from Department of Orthodontics, Peking University School and Hospital of Stomatology from May, 2006 to November, 2014 were classified into skeletal Class I (ANB 0°~5°, 1 317 subjects), Class II (ANB > 5°, 685 subjects) and Class III (ANB < 0°, 573 subjects) groups. CVM stages were evaluated with the modified version of CVM method. Independent sample t test was performed to analyze the difference of age at different CVM stages among various skeletal groups. Significant gender difference of age was found at CS3 to CS6 for skeletal Class I group (P < 0.05), at CS5 and CS6 for skeletal Class II group (P < 0.05), and at CS3 and CS5 for skeletal Class III group (P < 0.05). At CS3 stage, the average age of male in skeletal Class II and skeletal Class III groups was (11.6 ± 1.5) years old and (10.3 ± 1.9) years old, respectively; the average age of females in those two groups was (11.7 ± 1.3) years old and (9.3 ± 1.5) years old, respectively, and significant difference was found in both comparisons (P < 0.05). Compared average age at CS5 and CS6 between skeletal Class II and skeletal Class III groups [the ages of male was (15.1 ± 1.7) and (16.8 ± 1.6) years old, the ages of male was (14.6 ± 1.2) and (15.7 ± 2.5) years old], significant difference was also found (P < 0.05). Significant gender differences were found when evaluated CVM stage and age in skeletal Class I, II and III groups. Significant differences of age at different CVM stage was noted when skeletal Class II was compared with skeletal Class III groups.

  19. A comparison between cervical vertebrae and modified MP3 stages for the assessment of skeletal maturity.

    Science.gov (United States)

    Prasad, Mandava; Ganji, Venkata Suresh Kumar; George, Suja Ani; Talapaneni, Ashok Kumar; Shetty, Sharath Kumar

    2013-01-01

    Evaluation of skeletal maturity in human individuals is an important aspect in orthodontics and dentofacial orthopedics because, growth guidance and fundamental structural changes are essential for treatment of skeletal discrepancies in all the three planes. Among various growth assessment methods, cervical vertebra maturation stages and hand wrist have been correlated with the individual growth changes during puberty. The purpose of this study is to determine correlation of the CVM index with the modified median phalanx index (MP3) as described by Rajagopal and Kansal. 200 subjects (100 males and 100 females) of Nellore, Indian origin boys aged between 10 to 19 years and girls of 8 to 16 years were selected for the study. The subjects are selected randomly from patients visiting the Departments of Orthodontics and Dentofacial Orthopedics, Pediatric dentistry and Oral medicine and Radiology at Narayana Dental College and Hospital. Nellore. Radiographs of left hand MP3 and lateral cephalogram were taken. Cohen's kappa statistic was used to assess the agreement between the two measurements based on categorical variables. There was a good concordance between 6 stages of CVMI (Hassel and Farman) and the 6 stages of MP3 (Rajagopal and Kansal). Physiological maturity was earlier in females than in males when compared to the individuals of opposite sex of same chronological age. Chronological age was not a valid predictor of assessing the skeletal maturity because of significant variations in the distribution of CVMI and MP3 stages with respect to individual chronological age distribution.

  20. A Comparison of Skeletal Maturation assessed from MP3 and Its Correlation with Dental Maturation

    Directory of Open Access Journals (Sweden)

    Vishnu Vardhan Reddy

    2014-01-01

    Full Text Available To compare the various ossification stages of middle phalanges of third finger (MP3 and developmental stages of 2nd mandibular molar during the entire process of pubertal growth spurt. Evaluate the feasibility of recording MP3 stages using standard dental X-ray film. The mandibular 2nd molar exhibited highly significant correlation for both the males and females. This study showed a good correlation between the MP3 and dental maturity indicators. Therefore, 2nd molar tooth could be used as maturity indicator for the entire period of pubertal growth spurt. It can be used as an adjunct to the hand and wrist radiograph.

  1. Comparison of middle phalanx of the middle finger and cervical vertebrae as skeletal maturity indicators

    Directory of Open Access Journals (Sweden)

    Pavitra Tripura Javangula

    2017-01-01

    Full Text Available Objectives: To investigate the relationship between chronological age and the stages of maturation of cervical vertebrae maturation index (CVMI and the middle phalanx of the middle finger (MP3 and to determine the correlation between CVMI and MP3. Materials and Methods: A cross-sectional study included 100 children (boys - 50, girls - 50 aged 8–14 years based on nonprobability quota sampling. The study included digital radiographs of the MP3 of the right hand and conventional lateral cephalograms. Chronological age was assessed by the date of birth, MP3 maturation by Rajagopal and Kansal's criteria, and CVMI development by Hassel and Farman's method. Statistical Analysis: Spearman's rank-order correlation coefficient was applied to measure the association between stages of MP3 and CVMI. Results: Progressive stages of MP3 and CVMI were seen as chronological age advanced. Girls showed an advanced trend than boys in both MP3 and CVMI stages. MP3 and CVMI stages showed a strong positive correlation (r + 0.836, P < 0.01. Conclusions: MP3 and CVMI both are equally good indicators of skeletal maturity. Assessment of skeletal maturity on lateral cephalogram (CVMI is advantageous as it avoids the need for an additional radiograph.

  2. Method for assessment of skeletal maturity in children below one year of age

    Energy Technology Data Exchange (ETDEWEB)

    Erasmie, U.; Ringertz, H.

    1980-07-01

    Although there is a continuing clinical interest in the radiological determination of skeletal development in children below one year of age, none of the existing methods is particularly appropriate. We have therefore developed a new and simple method of assessment. This takes into account the dose of radiation and the two aspects of size and maturity of the skeleton; and so we choose to study the lateral view of the tarsus. The calcaneous and talus are ossification centers appearing before birth. The sum of length and height of these centers constitutes the first part of the assessment. The second part of our evaluation includes an appraisal of the cuboid, the third cuneiform and the distal epiphyses of tibia and fibula. For practical purposes we have chosen to relate the two different aspects of skeletal maturity which we have assessed to the weight of the baby.

  3. Determining skeletal maturation stage using cervical vertebrae: evaluation of three diagnostic methods

    Directory of Open Access Journals (Sweden)

    Luci Mara Fachardo Jaqueira

    2010-12-01

    Full Text Available The aim of the present study was to compare the use of three cervical vertebral evaluation methods (Hassel-Farman, Baccetti et al., and Seedat-Forsberg for determinating skeletal maturation stage in orthodontic patients. Twenty-three radiographs were randomly selected from a private orthodontic practice. Each radiograph was analyzed on three separate occasions by four evaluators (one radiologist and three orthodontists, who determined the skeletal maturation stage using the references established by each of the three methods. Intraevaluator and interevaluator comparisons were performed, and the degree of agreement was established using the weighted Kappa coefficient (95% CI. Good agreement (Kappa between 0.61 and 0.80 was observed between the determinations of most of the evaluators. The three methods demonstrated clinical applicability. However, the method proposed by Baccetti et al. achieved the best results, followed by the Hassel-Farman and the Seedat-Forsberg methods.

  4. Involvement of Rac1 and the actin cytoskeleton in insulin- and contraction-stimulated intracellular signaling and glucose uptake in mature skeletal muscle

    DEFF Research Database (Denmark)

    Sylow, Lykke

    understood. The aim of the current PhD was therefore to investigate the involvement of Rac1 and the actin cytoskeleton in the regulation of insulin- and contraction-stimulated glucose uptake in mature skeletal muscle. The central findings of this PhD thesis was that Rac1 was activated by both insulin...

  5. Physeal growth arrest after tibial lengthening in achondroplasia: 23 children followed to skeletal maturity.

    Science.gov (United States)

    Song, Sang-Heon; Agashe, Mandar Vikas; Huh, Young-Jae; Hwang, Soon-Young; Song, Hae-Ryong

    2012-06-01

    Bilateral tibial lengthening has become one of the standard treatments for upper segment-lower segment disproportion and to improve quality of life in achondroplasia. We determined the effect of tibial lengthening on the tibial physis and compared tibial growth that occurred at the physis with that in non-operated patients with achondroplasia. We performed a retrospective analysis of serial radiographs until skeletal maturity in 23 achondroplasia patients who underwent bilateral tibial lengthening before skeletal maturity (lengthening group L) and 12 achondroplasia patients of similar height and age who did not undergo tibial lengthening (control group C). The mean amount of lengthening of tibia in group L was 9.2 cm (lengthening percentage: 60%) and the mean age at the time of lengthening was 8.2 years. The mean duration of follow-up was 9.8 years. Skeletal maturity (fusion of physis) occurred at 15.2 years in group L and at 16.0 years in group C. The actual length of tibia (without distraction) at skeletal maturity was 238 mm in group L and 277 mm in group C (p = 0.03). The mean growth rates showed a decrease in group L relative to group C from about 2 years after surgery. Physeal closure was most pronounced on the anterolateral proximal tibial physis, with relative preservation of the distal physis. Our findings indicate that physeal growth rate can be disturbed after tibial lengthening in achondroplasia, and a close watch should be kept for such an occurrence-especially when lengthening of more than 50% is attempted.

  6. Second molar calcification stages to evaluate skeletal maturation: A cross-sectional radiographic study

    Directory of Open Access Journals (Sweden)

    U H Vijayashree

    2014-01-01

    Conclusion: A highly positive correlation exists between DI of mandibular second molars and CVMI. Stage F of Demirjian index, with the root length equal to or greater than the crown height corresponds to stage 3 of CVMI indicating the start of peak in mandibular growth which would be appropriate time to plan for functional appliances. Therefore, mandibular second molar calcification stages are reliable skeletal maturity indicator, which can be used to predict the growth status in determining the optimal treatment timing.

  7. Sagittal and Vertical Craniofacial Growth Pattern and Timing of Circumpubertal Skeletal Maturation: A Multiple Regression Study

    Directory of Open Access Journals (Sweden)

    Giuseppe Perinetti

    2016-01-01

    Full Text Available The knowledge of the associations between the timing of skeletal maturation and craniofacial growth is of primary importance when planning a functional treatment for most of the skeletal malocclusions. This cross-sectional study was thus aimed at evaluating whether sagittal and vertical craniofacial growth has an association with the timing of circumpubertal skeletal maturation. A total of 320 subjects (160 females and 160 males were included in the study (mean age, 12.3±1.7 years; range, 7.6–16.7 years. These subjects were equally distributed in the circumpubertal cervical vertebral maturation (CVM stages 2 to 5. Each CVM stage group also had equal number of females and males. Multiple regression models were run for each CVM stage group to assess the significance of the association of cephalometric parameters (ANB, SN/MP, and NSBa angles with age of attainment of the corresponding CVM stage (in months. Significant associations were seen only for stage 3, where the SN/MP angle was negatively associated with age (β coefficient, −0.7. These results show that hyperdivergent and hypodivergent subjects may have an anticipated and delayed attainment of the pubertal CVM stage 3, respectively. However, such association remains of little entity and it would become clinically relevant only in extreme cases.

  8. Sagittal and Vertical Craniofacial Growth Pattern and Timing of Circumpubertal Skeletal Maturation: A Multiple Regression Study

    Science.gov (United States)

    Rosso, Luigi; Riatti, Riccardo

    2016-01-01

    The knowledge of the associations between the timing of skeletal maturation and craniofacial growth is of primary importance when planning a functional treatment for most of the skeletal malocclusions. This cross-sectional study was thus aimed at evaluating whether sagittal and vertical craniofacial growth has an association with the timing of circumpubertal skeletal maturation. A total of 320 subjects (160 females and 160 males) were included in the study (mean age, 12.3 ± 1.7 years; range, 7.6–16.7 years). These subjects were equally distributed in the circumpubertal cervical vertebral maturation (CVM) stages 2 to 5. Each CVM stage group also had equal number of females and males. Multiple regression models were run for each CVM stage group to assess the significance of the association of cephalometric parameters (ANB, SN/MP, and NSBa angles) with age of attainment of the corresponding CVM stage (in months). Significant associations were seen only for stage 3, where the SN/MP angle was negatively associated with age (β coefficient, −0.7). These results show that hyperdivergent and hypodivergent subjects may have an anticipated and delayed attainment of the pubertal CVM stage 3, respectively. However, such association remains of little entity and it would become clinically relevant only in extreme cases. PMID:27995136

  9. Chronologic age and skeletal maturation of the cervical vertebrae and hand-wrist: is there a relationship?

    Science.gov (United States)

    Uysal, Tancan; Ramoglu, Sabri Ilhan; Basciftci, Faruk Ayhan; Sari, Zafer

    2006-11-01

    The aims of this study were (1) to investigate the relationship between chronologic age and maturation of cervical vertebrae, (2) to identify the relationship between chronologic age and maturation stage evaluated by hand-wrist radiographs, and (3) to determine whether the maturation of cervical vertebrae correlates with maturation indicated by hand-wrist radiographs in a Turkish population. The samples were derived from lateral cephalometric and hand-wrist radiographs of 503 subjects (213 male, 290 female; ages, 5.3-24.1 years). Cervical vertebral development was evaluated by the method of Hassel and Farman. Skeletal maturation of each hand-wrist radiograph was determined according to the method described by Björk and Grave, and Brown's system. The Spearman rank-order correlation coefficients were estimated separately for males and females to measure the relationships among chronologic age, cervical vertebral maturation, and the skeletal maturation measured at the hand-wrist. The Spearman correlation coefficients were 0.72 (P cervical vertebrae skeletal maturation, and 0.79 (P maturation via hand-wrist radiographs. The correlation coefficient between hand-wrist and cervical-vertebrae maturation was 0.86 (P cervical-vertebrae maturation stages are clinically useful maturity indicators of the pubertal growth period Turkish subjects.

  10. The association between skeletal maturation and adrenal androgen levels in obese children and adolescents

    Directory of Open Access Journals (Sweden)

    Sung Eun Kim

    2017-06-01

    Full Text Available PurposeThis study aimed to investigate the association between skeletal maturation and adrenal androgen levels in obese children and adolescents.MethodsFifty-three children and adolescents (aged 7–15 years diagnosed as obese or overweight were investigated. Anthropometric measurements, bone age (BA determination, serum biochemical analyses, and hormonal measurements were performed. The difference between BA and chronological age (BA–CA, dBACA was calculated and used to represent the degree of advanced skeletal maturation.ResultsThirty-one subjects were classified into the obese group and 22 subjects into the overweight group. Insulin resistance as calculated by the homeostasis model assessment of insulin resistance (HOMA-IR was significantly higher in the obese group than in the overweight group (4.03±2.20 vs. 2.86±1.11, P=0.026. The skeletal maturation of the obese group was advanced, but the dBACA did not differ between the obese and overweight groups statistically (1.43±1.35 vs. 0.91±1.15, P=0.141. Serum dehydroepiandrosterone sulfate (DHEA-S levels were significantly higher in subjects with dBACA>1 compared to those with dBACA≤1 (104.3±62.2 vs. 59.6±61.0, P=0.014. Correlation analyses demonstrated that dBACA was positively correlated with body mass index standard deviation scores (r=0.35, P=0.010, fasting insulin (r=0.36, P=0.009, HOMA-IR (r=0.30, P=0.031, and insulin-like growth factor-binding protein-3 (r=0.331, P=0.028. In multivariate linear regression analysis, HOMA-IR (P=0.026 and serum DHEA-S (P=0.032 were positively correlated with the degree of advanced skeletal maturation.ConclusionAdvanced skeletal maturation is associated with increased insulin resistance and elevated DHEA-S levels in obese children and adolescents.

  11. Comparative evaluation between cervical vertebral morphology and hand-wrist morphology for skeletal maturation assessment.

    Science.gov (United States)

    Grippaudo, C; Garcovich, D; Volpe, G; Lajolo, C

    2006-05-01

    The aim of the study was to find a correlation between the evaluation of skeletal maturation performed by the study of cervical vertebrae maturation indicators and the evaluation obtained by the hand and wrist maturation indicators. Left hand wrist radiographs and the corresponding lateral cephalograms of 90 patients (48 males and 42 females; aged 6 to 14 years) were paired and a study group of 128 pair of radiographs was obtained, having some patients 2 or more radiographs at different times. Hand and wrist radiographs were evaluated according to the protocol proposed by Grave (scores 0 to 9); corresponding lateral cephalograms were evaluated according to the method reported by Baccetti (scores 1 to 5). Values obtained with the 2 methods were analyzed by Spearman's correlation test. When the values were compared globally in the 2 genders a good correlation was obtained (r=0.795; Pmaturation evaluation by the analysis of cervical vertebrae in laterolateral cephalograms which can substitute the hand and wrist radiograph for the skeletal maturation evaluation in orthodontic diagnosis.

  12. Comparative evaluation of efficiency of serum IGF-1, hand-wrist radiographs, and cervical vertebrae as skeletal maturity indicator

    Directory of Open Access Journals (Sweden)

    Ritu Phogat

    2015-01-01

    Full Text Available Introduction: Accurate determination of skeletal maturity and remaining growth is crucial to identify optimal timing for the treatment of a series of dentoskeletal disharmonies in all three planes of space. Currently, cervical vertebral stages and hand-wrist radiographs are used to identify peak mandibular bone growth. Objectives: The main objective of this study was to compare and correlate insulin-like growth factor 1 (IGF-1 levels to skeletal maturation stages obtained by the cervical vertebral maturation method and skeletal maturational indicators obtained by the hand-wrist maturation method. Materials and Methods: In this cross-sectional study, serum IGF-1 level was measured for 53 healthy, North Indian subjects (26 female, 27 male, who were either about to begin orthodontic treatment, were undergoing treatment, or were in posttreatment follow-up between the ages of 9 and 20 years. For each subject, hand-wrist radiographs and lateral cephalograms were also obtained and staged. Results: The mean serum IGF-1 levels were the highest at the skeletal stages that were previously associated with the greatest amount of mandibular growth. Serum IGF-1 levels were low in the prepubertal skeletal stages, rise sharply to their peak in late puberty, and decline to approach prepubertal levels after puberty. Conclusion: Serum IGF-1 could be used as a skeletal maturity indicator and might be useful in detecting residual mandibular growth in young adults.

  13. Prediction of Curve Progression in Idiopathic Scoliosis: Validation of the Sanders Skeletal Maturity Staging System.

    Science.gov (United States)

    Sitoula, Prakash; Verma, Kushagra; Holmes, Laurens; Gabos, Peter G; Sanders, James O; Yorgova, Petya; Neiss, Geraldine; Rogers, Kenneth; Shah, Suken A

    2015-07-01

    Retrospective case series. This study aimed to validate the Sanders Skeletal Maturity Staging System and to assess its correlation to curve progression in idiopathic scoliosis. The Sanders Skeletal Maturity Staging System has been used to predict curve progression in idiopathic scoliosis. This study intended to validate that initial study with a larger sample size. We retrospectively reviewed 1100 consecutive patients with idiopathic scoliosis between 2005 and 2011. Girls aged 8 to 14 years (skeletal age and scoliosis curve magnitude were followed to skeletal maturity (Risser stage 5 or fully capped Risser stage 4), curve progression to 50° or greater, or spinal fusion. Patients with nonidiopathic curves were excluded. There were 161 patients: 131 girls (12.3 ± 1.2 yr) and 30 boys (13.9 ± 1.1 yr). The distribution of patients within Sanders stage (SS) 1 through 7 was 7, 28, 41, 45, 7, 31, and 2 patients, respectively; modified Lenke curve types 1 to 6 were 26, 12, 63, 5, 38, and 17 patients, respectively. All patients in SS2 with initial Cobb angles of 25° or greater progressed, and patients in SS1 and SS3 with initial Cobb angles of 35° or greater progressed. Similarly, all patients with initial Cobb angles of 40° or greater progressed except those in SS7. Conversely, none of the patients with initial Cobb angles of 15° or less or those in SS5, SS6, and SS7 with initial Cobb angles of 30° or less progressed. Predictive progression of 67%, 50%, 43%, 27%, and 60% was observed for subgroups SS1/30°, SS2/20°, SS3/30°, SS4/30°, and SS6/35° respectively. This larger cohort shows a strong predictive correlation between SS and initial Cobb angle for probability of curve progression in idiopathic scoliosis. 3.

  14. [Establishment of cervical vertebral skeletal maturation of female children in Shanghai].

    Science.gov (United States)

    Sun, Yan; Chen, Rong-jing; Yu, Quan; Fan, Li; Chen, Wei; Shen, Gang

    2009-06-01

    To establish a method for quantitatively evaluating skeletal maturation of cervical vertebrae of female children in Shanghai. The samples were selected from lateral cephalometric radiographs of 240 Shanghai girls, aged 8 to 15 years. The parameters were measured to indicate the morphological changes of the third (C3) and fourth (C4) vertebrae in width, height and the depth of the inferior curvature. The independent-sample t test and stepwise multiple regression analysis were used to estimate the growth status and the ratios of C3, C4 cervical vertebrae by SPSS 15.0 software package. The physical and morphological contour of C3, C4 cervical vertebrae increased proportionately with the increment of age. The regression formula for indicating cervical vertebral skeletal age of female children in Shanghai was expressed by the equation Y= -5.696+8.010 AH3/AP3+6.654 AH3/H3+6.045AH4/PH4 (r=0.912). The regression formula resulted from morphological measurements quantitatively indicates the skeletal maturation of cervical vertebrae of female children in Shanghai.

  15. An Automated System for Skeletal Maturity Assessment by Extreme Learning Machines

    Science.gov (United States)

    Mansourvar, Marjan; Shamshirband, Shahaboddin; Raj, Ram Gopal; Gunalan, Roshan; Mazinani, Iman

    2015-01-01

    Assessing skeletal age is a subjective and tedious examination process. Hence, automated assessment methods have been developed to replace manual evaluation in medical applications. In this study, a new fully automated method based on content-based image retrieval and using extreme learning machines (ELM) is designed and adapted to assess skeletal maturity. The main novelty of this approach is it overcomes the segmentation problem as suffered by existing systems. The estimation results of ELM models are compared with those of genetic programming (GP) and artificial neural networks (ANNs) models. The experimental results signify improvement in assessment accuracy over GP and ANN, while generalization capability is possible with the ELM approach. Moreover, the results are indicated that the ELM model developed can be used confidently in further work on formulating novel models of skeletal age assessment strategies. According to the experimental results, the new presented method has the capacity to learn many hundreds of times faster than traditional learning methods and it has sufficient overall performance in many aspects. It has conclusively been found that applying ELM is particularly promising as an alternative method for evaluating skeletal age. PMID:26402795

  16. An Automated System for Skeletal Maturity Assessment by Extreme Learning Machines.

    Science.gov (United States)

    Mansourvar, Marjan; Shamshirband, Shahaboddin; Raj, Ram Gopal; Gunalan, Roshan; Mazinani, Iman

    2015-01-01

    Assessing skeletal age is a subjective and tedious examination process. Hence, automated assessment methods have been developed to replace manual evaluation in medical applications. In this study, a new fully automated method based on content-based image retrieval and using extreme learning machines (ELM) is designed and adapted to assess skeletal maturity. The main novelty of this approach is it overcomes the segmentation problem as suffered by existing systems. The estimation results of ELM models are compared with those of genetic programming (GP) and artificial neural networks (ANNs) models. The experimental results signify improvement in assessment accuracy over GP and ANN, while generalization capability is possible with the ELM approach. Moreover, the results are indicated that the ELM model developed can be used confidently in further work on formulating novel models of skeletal age assessment strategies. According to the experimental results, the new presented method has the capacity to learn many hundreds of times faster than traditional learning methods and it has sufficient overall performance in many aspects. It has conclusively been found that applying ELM is particularly promising as an alternative method for evaluating skeletal age.

  17. Isolation and culture of primary osteocytes from the long bones of skeletally mature and aged mice

    Science.gov (United States)

    Stern, Amber Rath; Stern, Matthew M.; Van Dyke, Mark E.; Jähn, Katharina; Prideaux, Matthew; Bonewald, Lynda F.

    2013-01-01

    The purpose of this work was to establish a methodology to enable the isolation and study of osteocytes from skeletally mature young (4-month-old) and old (22-month-old) mice. The location of osteocytes deep within bone is ideal for their function as mechanosensors. However, this location makes the observation and study of osteocytes in vivo technically difficult. Osteocytes were isolated from murine long bones through a process of extended collagenase digestions combined with EDTA-based decalcification. A tissue homogenizer was used to reduce the remaining bone fragments to a suspension of bone particles, which were placed in culture to yield an outgrowth of osteocyte-like cells. All of the cells obtained from this outgrowth that displayed an osteocyte-like morphology stained positive for the osteocyte marker E11/GP38.[Q1] The osteocyte phenotype was further confirmed by a lack of staining for alkaline phosphatase and the absence of collagen1a1 expression. The outgrowth of osteocytes also expressed additional osteocyte-specific genes such as Sost and Mepe. This technique facilitates the isolation of osteocytes from skeletally mature bone. This novel enabling methodology should prove useful in advancing our understanding of the roles mature osteocytes play in bone health and disease. PMID:22668415

  18. Correlations of radiological assessment of skeletal maturity and orthopaedic injuries in the standardbred

    International Nuclear Information System (INIS)

    Pasolini, M.P.; Meomartino, L.; Fatone, G.; Brunetti, A.; Laratta, I.

    2003-01-01

    The aim of this study was to define a correlation between the incidence of orthopaedic injuries and the skeletal maturity, radiologically assessed, in a group of 23 standardbred horses. Starting at 18 months of age, radiograms of calcaneus and distal radial physis were taken at two months intervals, until X-ray evidence of closure. All the physis were blindly graded as: C: open physis; B-: initial evidence of central closure; B: partially closed physis; B+: full closure of the central portion of the physis; A: closed physis. Based on this classification, the horses were grouped as I (immature subject - C, B- and B), or M (mature subject - B+ and A). Orthopaedic injuries were classified as major lesion, if causing prolonged or definitive interruption of training, or minor, if causing brief or no interruption of training. Estimation of injury incidence in the different groups was calculated using the chi-square test (significance level P0.01). The average ages of physis closure (mean +- SD) were 24.1 +- 2.6 months (range 19-28), for the calcaneal physis, and 28.2 +- 2 months (range 26-33), for the distal radial physis, without significant differences between colts and fillies. In our study, according to a previous report, no correlation between X-ray skeletal maturity and incidence of orthopaedic injuries was demonstrated [it

  19. Is the cervical vertebral maturation (CVM) method effective enough to replace the hand-wrist maturation (HWM) method in determining skeletal maturation?-A systematic review.

    Science.gov (United States)

    Szemraj, Agnieszka; Wojtaszek-Słomińska, Anna; Racka-Pilszak, Bogna

    2018-05-01

    Chronological age provides only general information on the development of a child/adolescent. However, the biological age of the patient is more significant. One of the methods is the determination of the bone age based on the development of the hand and wrist bones. In 1972 a method for assessing cervical vertebral maturation on the cephalometric radiographs was introduced (CVM method). As a result, additional patient radiation was eliminated. Currently, this type of radiograph is routinely applied in orthodontic treatment. The aim of the study was to assess the usefulness of the CVM method and to verify the assumption, according to which the CVM method modified by Baccetti et al. may replace the method for the assessment of skeletal maturation based on a hand-wrist X-ray, which is known as the hand-wrist maturation (HWM) method. The present study reviewed the literature between 2006 and 2016. In the first stage of selection 905 articles were obtained. Finally, 10 articles were enrolled for the review. All of the studies presented a high level of correlation between the examined methods. In eight articles the researchers admitted that the CVM classification could replace the HWM method, known as the "gold standard". In two studies , the researchers suggested considering the CVM method an additional method despite its compatibility and usefulness. The lowest correlation coefficient was 0.616 and the highest 0.937. The assessment of the skeletal age with the CVM is done on a cephalometric radiograph, routinely used in orthodontic practice, which makes it easy to apply. The determination of features of only C2, C3 and C4 vertebrae is possible even if the patient wears an X-ray protective thyroid collar. Therefore, the radiation dose is minimized. The CVM method shows a high level of correlation with the HWM method. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. The BoneXpert method for automated determination of skeletal maturity

    DEFF Research Database (Denmark)

    Thodberg, Hans Henrik; Kreiborg, Sven; Juul, Anders

    2009-01-01

    Bone age rating is associated with a considerable variability from the human interpretation, and this is the motivation for presenting a new method for automated determination of bone age (skeletal maturity). The method, called BoneXpert, reconstructs, from radiographs of the hand, the borders...... component analysis; 3) the consensus bone age concept that defines bone age of each bone as the best estimate of the bone age of the other bones in the hand; 4) a common bone age model for males and females; and 5) the unified modelling of TW and GP bone age. BoneXpert is developed on 1559 images...

  1. Craniofacial changes in Class III malocclusion as related to skeletal and dental maturation.

    Science.gov (United States)

    Baccetti, Tiziano; Reyes, Brian C; McNamara, James A

    2007-08-01

    In this large cross-sectional study, we aimed to analyze growth trends in white subjects with Class III malocclusion using both skeletal and dental maturation staging. The sample consisted of 1091 pretreatment lateral cephalometric records of Class III patients (560 female, 531 male). Cephalometric dentoskeletal measurements were compared at subsequent stages in cervical vertebral maturation and Hellman's categorization of dental development by means of ANOVA with Bonferroni post-hoc tests in both sexes separately. The findings indicated that, in Class III malocclusion, the pubertal peak in mandibular growth occurs between stages 3 and 4 of cervical vertebral maturation, with average increases in total mandibular length of about 8 and 5.5 mm in Class III boys and girls, respectively. Significant changes in total mandibular length occur until young adulthood (18 years on average), with increases between late maturation stages (4 through 6) that were twice as large as in subjects with normal occlusion for the Class III females, and 3 times as large as in subjects with normal occlusion for the Class III males. Growth trends toward accentuated Class III profile and increased vertical dimension of the face also become apparent at late developmental stages (corresponding with complete eruption of the second and third molars).

  2. Assessment of skeletal maturation with permanent mandibular second molar calcification stages among a group of Nepalese orthodontic patients

    Directory of Open Access Journals (Sweden)

    Giri J

    2016-03-01

    Full Text Available Jamal Giri,1 Basanta Kumar Shrestha,2 Rajiv Yadav,2 Tika Ram Ghimire21Department of Orthodontics, BP Koirala Institute of Health Sciences, Dharan, 2Department of Dentistry, Institute of Medicine, Kathmandu, Nepal Background: Assessment of growth status of a patient is a key component in orthodontic diagnosis and treatment planning for growing patients with skeletal discrepancy. Skeletal maturation based on hand-wrist radiograph and cervical vertebral maturation (CVM are commonly used methods of growth assessment. Studies have shown that stages of dental calcification can also be used to assess skeletal maturation status of an individual, whereas other studies have suggested that the relationship between dental calcification and skeletal maturation should be interpreted with caution owing to racial variation. Objective: To evaluate the relationship between permanent mandibular second molar calcification stages and skeletal maturity assessed by CVM among a group of Nepalese orthodontic patients. Materials and methods: One hundred and sixty-eight digital radiographs (84 orthopantomograms and 84 lateral cephalograms were obtained from the records of 84 patients who sought orthodontic treatment in Orthodontic and Dentofacial Orthopaedic Unit, Department of Dentistry, Institute of Medicine, Kathmandu. Two parameters were used in this study, namely, CVM stages from lateral cephalogram and Demirjian index (DI stages from orthopantomogram. The evaluation of digital radiographs was carried out on a computer screen with a resolution of 1,280×800 pixels. The association between DI stages of permanent mandibular second molar and CVM stages was assessed. Results: A statistically significant association was found between DI and CVM stages for both male and female subjects with Pearson's contingency coefficient value of 0.751 and 0.766 for male and female subjects, respectively. Conclusion: Skeletal maturation can be reliably assessed with dental calcification

  3. Thumb Ossification Composite Index (TOCI) for Predicting Peripubertal Skeletal Maturity and Peak Height Velocity in Idiopathic Scoliosis: A Validation Study of Premenarchal Girls with Adolescent Idiopathic Scoliosis Followed Longitudinally Until Skeletal Maturity.

    Science.gov (United States)

    Hung, Alec L H; Chau, W W; Shi, B; Chow, Simon K; Yu, Fiona Y P; Lam, T P; Ng, Bobby K W; Qiu, Y; Cheng, Jack C Y

    2017-09-06

    Accurate skeletal maturity assessment is important to guide clinical evaluation of idiopathic scoliosis, but commonly used methods are inadequate or too complex for rapid clinical use. The objective of the study was to propose a new simplified staging method, called the thumb ossification composite index (TOCI), based on the ossification pattern of the 2 thumb epiphyses and the adductor sesamoid bone; to determine its accuracy in predicting skeletal maturation when compared with the Sanders simplified skeletal maturity system (SSMS); and to validate its interrater and intrarater reliability. Hand radiographs of 125 girls, acquired when they were newly diagnosed with idiopathic scoliosis prior to menarche and during longitudinal follow-up until skeletal maturity (a minimum of 4 years), were scored with the TOCI and SSMS. These scores were compared with digital skeletal age (DSA) and radius, ulna, and small hand bones (RUS) scores; anthropometric data; peak height velocity; and growth-remaining profiles. Correlations were analyzed with the chi-square test, Spearman and Cramer V correlation methods, and receiver operating characteristic curve analysis. Reliability analysis using the intraclass correlation (ICC) was conducted. Six hundred and forty-five hand radiographs (average, 5 of each girl) were scored. The TOCI staging system was highly correlated with the DSA and RUS scores (r = 0.93 and 0.92, p systems predicted peak height velocity with comparable accuracy, with a strong Cramer V association (0.526 and 0.466, respectively; p 0.97. The new proposed TOCI could provide a simplified staging system for the assessment of skeletal maturity of subjects with idiopathic scoliosis. The index needs to be subjected to further multicenter validation in different ethnic groups.

  4. A Comparison of Hand Wrist Bone Analysis with Two Different Cervical Vertebral Analysis in Measuring Skeletal Maturation

    Science.gov (United States)

    Pichai, Saravanan; Rajesh, M; Reddy, Naveen; Adusumilli, Gopinath; Reddy, Jayaprakash; Joshi, Bhavana

    2014-01-01

    Background: Skeletal maturation is an integral part of individual pattern of growth and development and is a continuous process. Peak growth velocity in standing height is the most valid representation of the rate of overall skeletal growth. Ossification changes of hand wrist and cervical vertebrae are the reliable indicators of growth status of individual. The objective of this study was to compare skeletal maturation as measured by hand wrist bone analysis and cervical vertebral analysis. Materials and Methods: Hand wrist radiographs and lateral cephalograms of 72 subjects aged between 7 and 16 years both male and female from the patients visiting Department of Orthodontics and Dentofacial Orthopedics, R.V. Dental College and Hospital. The 9 stages were reduced to 5 stages to compare with cervical vertebral maturation stage by Baccetti et al. The Bjork, Grave and Brown stages were reduced to six intervals to compare with cervical vertebral maturational index (CVMI) staging by Hassel and Farman. These measurements were then compared with the hand wrist bone analysis, and the results were statistically analyzed using the Mann–Whitney test. Results: There was no significant difference between the hand wrist analysis and the two different cervical vertebral analyses for assessing skeletal maturation. There was no significant difference between the two cervical vertebral analyses, but the CVMI method, which is visual method is less time consuming. Conclusion: Vertebral analysis on a lateral cephalogram is as valid as the hand wrist bone analysis with the advantage of reducing the radiation exposure of growing subjects. PMID:25395791

  5. A comparison of hand wrist bone analysis with two different cervical vertebral analysis in measuring skeletal maturation.

    Science.gov (United States)

    Pichai, Saravanan; Rajesh, M; Reddy, Naveen; Adusumilli, Gopinath; Reddy, Jayaprakash; Joshi, Bhavana

    2014-09-01

    Skeletal maturation is an integral part of individual pattern of growth and development and is a continuous process. Peak growth velocity in standing height is the most valid representation of the rate of overall skeletal growth. Ossification changes of hand wrist and cervical vertebrae are the reliable indicators of growth status of individual. The objective of this study was to compare skeletal maturation as measured by hand wrist bone analysis and cervical vertebral analysis. Hand wrist radiographs and lateral cephalograms of 72 subjects aged between 7 and 16 years both male and female from the patients visiting Department of Orthodontics and Dentofacial Orthopedics, R.V. Dental College and Hospital. The 9 stages were reduced to 5 stages to compare with cervical vertebral maturation stage by Baccetti et al. The Bjork, Grave and Brown stages were reduced to six intervals to compare with cervical vertebral maturational index (CVMI) staging by Hassel and Farman. These measurements were then compared with the hand wrist bone analysis, and the results were statistically analyzed using the Mann-Whitney test. There was no significant difference between the hand wrist analysis and the two different cervical vertebral analyses for assessing skeletal maturation. There was no significant difference between the two cervical vertebral analyses, but the CVMI method, which is visual method is less time consuming. Vertebral analysis on a lateral cephalogram is as valid as the hand wrist bone analysis with the advantage of reducing the radiation exposure of growing subjects.

  6. Silychristin: Skeletal Alterations and Biological Activities

    Czech Academy of Sciences Publication Activity Database

    Biedermann, David; Buchta, M.; Holečková, Veronika; Sedlák, David; Valentová, Kateřina; Cvačka, Josef; Bednárová, Lucie; Křenková, Alena; Kuzma, Marek; Škuta, Ctibor; Peikerová, Žaneta; Bartůněk, Petr; Křen, Vladimír

    2016-01-01

    Roč. 79, č. 12 (2016), s. 3086-3092 ISSN 0163-3864 R&D Projects: GA ČR(CZ) GA15-03037S; GA MZd(CZ) NV16-27317A; GA MŠk LO1220; GA MŠk LM2015063; GA MŠk(CZ) LD15081 Institutional support: RVO:61388971 ; RVO:68378050 ; RVO:61388963 Keywords : Silychristin * skeletal alterations * biological activities Subject RIV: CC - Organic Chemistry Impact factor: 3.281, year: 2016

  7. Digital radiograph of the middle phalanx of the third finger (MP3 region as a tool for skeletal maturity assessment

    Directory of Open Access Journals (Sweden)

    Deepa Y Hegde

    2012-01-01

    Results: The correlation determined between the MP3 stages and cervical vertebrae maturity index (CVMI stages, the peak-wise distribution of the MP3 stages, and the correlation between the MP3 stages and the chronological age were found to be highly significant. Conclusions: Digital radiograph of the MP3 region is definitely a simple, reliable, cost-effective, and time-saving technique for the assessment of skeletal maturity.

  8. Skeletal Maturation and Mineralisation of Children with Moderate to Severe Spastic Quadriplegia

    Science.gov (United States)

    Sitaraman, Sadasivan

    2016-01-01

    Introduction Diminished bone mineral density and delayed skeletal maturation are common in children with spastic quadriplegia. Aim The purpose of our study was to evaluate the Bone Mineral Density (BMD) of children with moderate to severe spastic quadriplegia and its relationship with other variables like nutrition and growth. Materials and Methods This was a hospital based, cross- sectional, case-control study. Forty-two (28 males, 14 females) children with spastic quadriplegia and 42 (24 males, 18 females) healthy children were included in the study. BMD of cases and control were measured by Dual Energy X-ray Absorptiometry (DEXA). Radiographs of left hand and wrist of cases and controls were taken and bone age was determined. Results BMD values of upper extremity, lower extremity, thoraco-lumbar spine and pelvis in cases were lower than those of controls (p quadriplegia and nutritional status is an important contributing factor. PMID:27504366

  9. Radiological findings for hip dysplasia at skeletal maturity. Validation of digital and manual measurement techniques

    Energy Technology Data Exchange (ETDEWEB)

    Engesaeter, Ingvild Oevsteboe [University of Bergen, Department of Surgical Sciences, Bergen (Norway); Haukeland University Hospital, Department of Orthopaedic Surgery, Bergen (Norway); Haukeland University Hospital, Department of Radiology, Bergen (Norway); Haukeland University Hospital, The Norwegian Arthroplasty Register, Department of Orthopaedic Surgery, Bergen (Norway); Laborie, Lene Bjerke; Rosendahl, Karen [University of Bergen, Department of Surgical Sciences, Bergen (Norway); Haukeland University Hospital, Department of Radiology, Bergen (Norway); Lehmann, Trude Gundersen; Fevang, Jonas; Engesaeter, Lars Birger [University of Bergen, Department of Surgical Sciences, Bergen (Norway); Haukeland University Hospital, Department of Orthopaedic Surgery, Bergen (Norway); Sera, Francesco [University College London Institute of Child Health, Medical Research Council Centre of Epidemiology for Child Health, London (United Kingdom); Pedersen, Douglas; Morcuende, Jose [University of Iowa Hospital and Clinics, Department of Orthopaedics and Rehabilitation, Iowa City, IA (United States); Lie, Stein Atle [Uni Health, Uni Research, Bergen (Norway)

    2012-07-15

    To report on intra-observer, inter-observer, and inter-method reliability and agreement for radiological measurements used in the diagnosis of hip dysplasia at skeletal maturity, as obtained by a manual and a digital measurement technique. Pelvic radiographs from 95 participants (56 females) in a follow-up hip study of 18- to 19-year-old patients were included. Eleven radiological measurements relevant for hip dysplasia (Sharp's, Wiberg's, and Ogata's angles; acetabular roof angle of Toennis; articulo-trochanteric distance; acetabular depth-width ratio; femoral head extrusion index; maximum teardrop width; and the joint space width in three different locations) were validated. Three observers measured the radiographs using both a digital measurement program and manually in AgfaWeb1000. Inter-method and inter- and intra-observer agreement were analyzed using the mean differences between the readings/readers, establishing the 95% limits of agreement. We also calculated the minimum detectable change and the intra-class correlation coefficient. Large variations among different radiological measurements were demonstrated. However, the variation was not related to the use of either the manual or digital measurement technique. For measurements with greater absolute values (Sharp's angle, femoral head extrusion index, and acetabular depth-width ratio) the inter- and intra-observer and inter-method agreements were better as compared to measurements with lower absolute values (acetabular roof angle, teardrop and joint space width). The inter- and intra-observer variation differs notably across different radiological measurements relevant for hip dysplasia at skeletal maturity, a fact that should be taken into account in clinical practice. The agreement between the manual and digital methods is good. (orig.)

  10. Radiological findings for hip dysplasia at skeletal maturity. Validation of digital and manual measurement techniques.

    Science.gov (United States)

    Engesæter, Ingvild Øvstebø; Laborie, Lene Bjerke; Lehmann, Trude Gundersen; Sera, Francesco; Fevang, Jonas; Pedersen, Douglas; Morcuende, José; Lie, Stein Atle; Engesæter, Lars Birger; Rosendahl, Karen

    2012-07-01

    To report on intra-observer, inter-observer, and inter-method reliability and agreement for radiological measurements used in the diagnosis of hip dysplasia at skeletal maturity, as obtained by a manual and a digital measurement technique. Pelvic radiographs from 95 participants (56 females) in a follow-up hip study of 18- to 19-year-old patients were included. Eleven radiological measurements relevant for hip dysplasia (Sharp's, Wiberg's, and Ogata's angles; acetabular roof angle of Tönnis; articulo-trochanteric distance; acetabular depth-width ratio; femoral head extrusion index; maximum teardrop width; and the joint space width in three different locations) were validated. Three observers measured the radiographs using both a digital measurement program and manually in AgfaWeb1000. Inter-method and inter- and intra-observer agreement were analyzed using the mean differences between the readings/readers, establishing the 95% limits of agreement. We also calculated the minimum detectable change and the intra-class correlation coefficient. Large variations among different radiological measurements were demonstrated. However, the variation was not related to the use of either the manual or digital measurement technique. For measurements with greater absolute values (Sharp's angle, femoral head extrusion index, and acetabular depth-width ratio) the inter- and intra-observer and inter-method agreements were better as compared to measurements with lower absolute values (acetabular roof angle, teardrop and joint space width). The inter- and intra-observer variation differs notably across different radiological measurements relevant for hip dysplasia at skeletal maturity, a fact that should be taken into account in clinical practice. The agreement between the manual and digital methods is good.

  11. A radiographic comparative study of two series of skeletally mature clubfeet treated by two different protocols

    Energy Technology Data Exchange (ETDEWEB)

    Ippolito, E.; Caterini, R.; Farsetti, P. [Department of Orthopaedic Surgery, University of Rome ' ' Tor Vergata' ' , Via della Ricerca Scientifica 135, 00173, Rome (Italy); Fraracci, L.; Di Mario, M. [Department of Radiology, IRCCS Santa Lucia Institute, Via Ardeatina 306, 00179, Rome (Italy)

    2003-08-01

    To compare the radiographic features of two series of congenital clubfeet to determine whether a different treatment protocol may influence the radiographic results at the end of skeletal growth. Two series of patients with congenital clubfeet, treated by two different manipulative techniques and by two different complementary soft tissue release operations, were radiographically studied at skeletal maturity. Twenty-one normal feet of the unilateral cases in both series served as controls. Anteroposterior and lateral radiographs of the feet were taken with the patient standing, and several radiographic parameters were studied. The size of the talus and calcaneus and the height of the talar trochlea were smaller than normal in all cases of clubfeet, were similar in both series and were not influenced by treatment, whereas all the other radiographic parameters studied were more or less different between the two series and seemed to be influenced by treatment. In no treated clubfoot of either series was a normal radiographic foot anatomy restored, not even in those feet that had an excellent clinical result. (orig.)

  12. A radiographic comparative study of two series of skeletally mature clubfeet treated by two different protocols

    International Nuclear Information System (INIS)

    Ippolito, E.; Caterini, R.; Farsetti, P.; Fraracci, L.; Di Mario, M.

    2003-01-01

    To compare the radiographic features of two series of congenital clubfeet to determine whether a different treatment protocol may influence the radiographic results at the end of skeletal growth. Two series of patients with congenital clubfeet, treated by two different manipulative techniques and by two different complementary soft tissue release operations, were radiographically studied at skeletal maturity. Twenty-one normal feet of the unilateral cases in both series served as controls. Anteroposterior and lateral radiographs of the feet were taken with the patient standing, and several radiographic parameters were studied. The size of the talus and calcaneus and the height of the talar trochlea were smaller than normal in all cases of clubfeet, were similar in both series and were not influenced by treatment, whereas all the other radiographic parameters studied were more or less different between the two series and seemed to be influenced by treatment. In no treated clubfoot of either series was a normal radiographic foot anatomy restored, not even in those feet that had an excellent clinical result. (orig.)

  13. Short-term secular change in height, body mass and Tanner-Whitehouse 3 skeletal maturity of Madeira youth, Portugal.

    Science.gov (United States)

    Freitas, Duarte; Malina, Robert M; Maia, José; Lefevre, Johan; Stasinopoulos, Mikis; Gouveia, Élvio; Claessens, Albrecht; Thomis, Martine; Lausen, Berthold

    2012-05-01

    Secular trends in height and weight are reasonably well documented in Europe. Corresponding observations for skeletal maturation are lacking. To assess secular trends in height, body mass and skeletal maturity of Portuguese children and adolescents and to provide updated reference values for skeletal maturity scores (SMSs). Data for 2856 children and adolescents of 4-17 years, 1412 boys and 1444 girls, from The 'Madeira Growth Study' (MGS; 1996-1998) and from the'Healthy Growth of Madeira Children Study' (CRES; 2006) were used. Height and body mass were measured. Skeletal maturity was assessed with the Tanner-Whitehouse 2 and 3 methods. Children from CRES were taller and heavier than peers from MGS. Differences in height reached 5.8 cm in boys and 5.5 cm in girls. RUS SMSs did not differ consistently between surveys boys, while higher RUS scores were observed in CRES girls. Adult RUS SMSs for MGS and CRES combined were attained at 15.8 years in boys and 14.8 years in girls. Corresponding ages for adult Carpal SMSs were 14.4 and 14.0, respectively. The short-term trends for height and mass were not entirely consistent with the trends in RUS and Carpal SMSs and SAs.

  14. In vivo generation of a mature and functional artificial skeletal muscle.

    Science.gov (United States)

    Fuoco, Claudia; Rizzi, Roberto; Biondo, Antonella; Longa, Emanuela; Mascaro, Anna; Shapira-Schweitzer, Keren; Kossovar, Olga; Benedetti, Sara; Salvatori, Maria L; Santoleri, Sabrina; Testa, Stefano; Bernardini, Sergio; Bottinelli, Roberto; Bearzi, Claudia; Cannata, Stefano M; Seliktar, Dror; Cossu, Giulio; Gargioli, Cesare

    2015-04-01

    Extensive loss of skeletal muscle tissue results in mutilations and severe loss of function. In vitro-generated artificial muscles undergo necrosis when transplanted in vivo before host angiogenesis may provide oxygen for fibre survival. Here, we report a novel strategy based upon the use of mouse or human mesoangioblasts encapsulated inside PEG-fibrinogen hydrogel. Once engineered to express placental-derived growth factor, mesoangioblasts attract host vessels and nerves, contributing to in vivo survival and maturation of newly formed myofibres. When the graft was implanted underneath the skin on the surface of the tibialis anterior, mature and aligned myofibres formed within several weeks as a complete and functional extra muscle. Moreover, replacing the ablated tibialis anterior with PEG-fibrinogen-embedded mesoangioblasts also resulted in an artificial muscle very similar to a normal tibialis anterior. This strategy opens the possibility for patient-specific muscle creation for a large number of pathological conditions involving muscle tissue wasting. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

  15. Skeletal maturation in individuals with Down's syndrome: Comparison between PGS curve, cervical vertebrae and bones of the hand and wrist

    Directory of Open Access Journals (Sweden)

    Glauber Carinhena

    2014-08-01

    Full Text Available INTRODUCTION: This study was conducted with the aim of adapting the methods developed by Martins and Sakima to assess skeletal maturation by cervical vertebrae in the pubertal growth spurt (PGS curve. It also aimed to test the reliability and agreement between those methods and the method of hand and wrist radiograph when compared two by two and all together. METHODS: The sample comprised 72 radiographs, with 36 lateral radiographs of the head and 36 hand-wrist radiographs of 36 subjects with Down's syndrome (DS, 13 female and 23 male, aged between 8 years and 6 months and 18 years and 7 months, with an average age of 13 years and 10 months. RESULTS AND CONCLUSIONS: Results revealed that adapting the methods developed by Martins and Sakima to assess skeletal maturation by cervical vertebrae in the curve of PGS is practical and useful in determining the stage of growth and development of individuals. The stages of maturation evaluated by cervical vertebrae and ossification centers observed in radiographs of the hand and wrist were considered reliable, with excellent level of agreement between the methods by Hassel and Farman as well as Baccetti, Franchi and McNamara Jr and Martins and Sakima. Additionally, results revealed an agreement that ranged between reasonable to good for the three methods used to assess the skeletal maturation, showing statistical significance.

  16. Skeletal maturation in individuals with Down's syndrome: Comparison between PGS curve, cervical vertebrae and bones of the hand and wrist

    Science.gov (United States)

    Carinhena, Glauber; Siqueira, Danilo Furquim; Sannomiya, Eduardo Kazuo

    2014-01-01

    Introduction This study was conducted with the aim of adapting the methods developed by Martins and Sakima to assess skeletal maturation by cervical vertebrae in the pubertal growth spurt (PGS) curve. It also aimed to test the reliability and agreement between those methods and the method of hand and wrist radiograph when compared two by two and all together. Methods The sample comprised 72 radiographs, with 36 lateral radiographs of the head and 36 hand-wrist radiographs of 36 subjects with Down's syndrome (DS), 13 female and 23 male, aged between 8 years and 6 months and 18 years and 7 months, with an average age of 13 years and 10 months. Results and Conclusions Results revealed that adapting the methods developed by Martins and Sakima to assess skeletal maturation by cervical vertebrae in the curve of PGS is practical and useful in determining the stage of growth and development of individuals. The stages of maturation evaluated by cervical vertebrae and ossification centers observed in radiographs of the hand and wrist were considered reliable, with excellent level of agreement between the methods by Hassel and Farman as well as Baccetti, Franchi and McNamara Jr and Martins and Sakima. Additionally, results revealed an agreement that ranged between reasonable to good for the three methods used to assess the skeletal maturation, showing statistical significance. PMID:25279522

  17. A comparison of hand-wrist bone and cervical vertebral analyses in measuring skeletal maturation.

    Science.gov (United States)

    Gandini, Paola; Mancini, Marta; Andreani, Federico

    2006-11-01

    To compare skeletal maturation as measured by hand-wrist bone analysis and by cervical vertebral analysis. A radiographic hand-wrist bone analysis and cephalometric cervical vertebral analysis of 30 patients (14 males and 16 females; 7-18 years of age) were examined. The hand-wrist bone analysis was evaluated by the Bjork index, whereas the cervical vertebral analysis was assessed by the cervical vertebral maturation stage (CVMS) method. To define vertebral stages, the analysis consisted of both cephalometric (13 points) and morphologic evaluation of three cervical vertebrae (concavity of second, third, and fourth vertebrae and shape of third and fourth vertebrae). These measurements were then compared with the hand-wrist bone analysis, and the results were statistically analyzed by the Cohen kappa concordance index. The same procedure was repeated after 6 months and showed identical results. The Cohen kappa index obtained (mean +/- SD) was 0.783 +/- 0.098, which is in the significant range. The results show a concordance of 83.3%, considering that the estimated percentage for each case is 23.3%. The results also show a correlation of CVMS I with Bjork stages 1-3 (interval A), CVMS II with Bjork stage 4 (interval B), CVMS III with Bjork stage 5 (interval C), CVMS IV with Bjork stages 6 and 7 (interval D), and CVMS V with Bjork stages 8 and 9 (interval E). Vertebral analysis on a lateral cephalogram is as valid as the hand-wrist bone analysis with the advantage of reducing the radiation exposure of growing subjects.

  18. The relationship determination between menarche and the peak of skeletal maturation using hand wrist and cervical vertebrae index

    Directory of Open Access Journals (Sweden)

    Endah Mardiati

    2014-06-01

    Full Text Available Background: Menarche and skeletal maturation indices are physiological maturation indicators that can be used to establish the maturation stage of individual patient in orthodontic treatment, especially in orthodontic growth modification and orthognatic surgery. Purpose: The purpose of this study was to determine the relationship between menarche and the peak of skeletal maturation using hand-wrist and cervical vertebrae indexes. Methods: This was an observational diagnostic research with 220 female of Deutero-Malay Indonesian subjects aged 8-17 years from Dental Hospital Faculty of Dentistry Universitas Padjadjaran, and some privates orthodontic practice in Bandung. All subjects had hand-wrist radiograph and lateral cephalogram. Menarche data were collected through interview with the subjects and their parents. There were 89 subjects who already had menarche but only 84 of them remembered the month and year of their menarche. The stage of hand-wrist skeletal maturation was analyzed using Fishman method and cervical vertebrae maturation was analyzed using Baccetty et.al., method. Results: The result indicates that the menarche age of Indonesian DeuteroMalay subject were 12.47 ± 0.73 year. The youngest age of were 10.92 ± 0.0 year and the oldest were 13.83 ± 0.23 year. Conclusion: Menarche could be used as an indicator that the pubertal growth peak has been exceeded and to predict the end of the pubertal growth. This study showed that 0.49 years after MP3cap stage of hand-wrist skeletal maturation index and 0.69 years after CVMS2 stage of cervical vertebrae skeletal maturation index, the subject of Indonesian Deutero-Malay will have their menarche. Latar belakang: Menarke dan indeks maturasi skeletal merupakan indikator maturasi fisologis yang dapat digunakan untuk menentukan tahap maturasi pasien pada perawatan ortodonti modifikasi pertumbuhan dan bedah ortognati. Tujuan: Tujuan penelitian ini adalah menentukan hubungan antara menarke dengan

  19. A comparative study of dentoskeletal changes of herbst appliance treatment among different skeletal maturity groups based on cervical vertebral maturation

    Directory of Open Access Journals (Sweden)

    Bodore K Albaker

    2012-01-01

    exhibited more proclination of the lower incisors than the pre-peak and peak groups (P <0.05. The results suggest that treatment of skeletal Class II malocclusion with the Herbst appliance is best during the peak growth spurt corresponding to CVM Stage 3-4.

  20. The developmental stages of the middle phalanx of the third finger (MP3): a sole indicator in assessing the skeletal maturity?

    Science.gov (United States)

    Madhu, S; Hegde, Amitha M; Munshi, A K

    2003-01-01

    Assessment of skeletal maturity is an integral part of interceptive diagnosis and treatment planning. The present day methods of skeletal maturity assessment like the hand-wrist radiographs or cervical vertebrae radiographs are expensive, require elaborate equipment and accounts for high radiation exposure, especially for growing children. The present study was thus undertaken to provide a simple and practical method of skeletal maturity assessment using the developmental stages of the middle phalanx of the third finger (MP3) as seen on an IOPA film taken using a standard dental x-ray machine. The results of the study showed that this simple method was highly reliable and could be used as an alternative method to assess the skeletal maturity of growing children.

  1. Early life vitamin D depletion alters the postnatal response to skeletal loading in growing and mature bone

    Science.gov (United States)

    Buckley, Harriet; Owen, Robert; Marin, Ana Campos; Lu, Yongtau; Eyles, Darryl; Lacroix, Damien; Reilly, Gwendolen C.; Skerry, Tim M.; Bishop, Nick J.

    2018-01-01

    There is increasing evidence of persistent effects of early life vitamin D exposure on later skeletal health; linking low levels in early life to smaller bone size in childhood as well as increased fracture risk later in adulthood, independently of later vitamin D status. A major determinant of bone mass acquisition across all ages is mechanical loading. We tested the hypothesis in an animal model system that early life vitamin D depletion results in abrogation of the response to mechanical loading, with consequent reduction in bone size, mass and strength during both childhood and adulthood. A murine model was created in which pregnant dams were either vitamin D deficient or replete, and their offspring moved to a vitamin D replete diet at weaning. Tibias of the offspring were mechanically loaded and bone structure, extrinsic strength and growth measured both during growth and after skeletal maturity. Offspring of vitamin D deplete mice demonstrated lower bone mass in the non loaded limb and reduced bone mass accrual in response to loading in both the growing skeleton and after skeletal maturity. Early life vitamin D depletion led to reduced bone strength and altered bone biomechanical properties. These findings suggest early life vitamin D status may, in part, determine the propensity to osteoporosis and fracture that blights later life in many individuals. PMID:29370213

  2. How is AMPK activity regulated in skeletal muscles during exercise?

    DEFF Research Database (Denmark)

    Jørgensen, Sebastian Beck; Rose, Adam John

    2008-01-01

    AMPK is a metabolic "master" controller activated in skeletal muscle by exercise in a time and intensity dependent manner, and has been implicated in regulating metabolic pathways in muscle during physical exercise. AMPK signaling in skeletal muscle is regulated by several systemic...... and intracellular factors and the regulation of skeletal muscle AMPK in response to exercise is the focus of this review. Specifically, the role of LKB1 and phosphatase PP2C in nucleotide-dependent activation of AMPK, and ionized calcium in CaMKK-dependent activation of AMPK in working muscle is discussed. We also...

  3. Digital radiograph of the middle phalanx of the third finger (MP3) region as a tool for skeletal maturity assessment.

    Science.gov (United States)

    Hegde, Deepa Y; Baliga, Sudhindra; Yeluri, Ramakrishna; Munshi, A K

    2012-01-01

    To evaluate the reliability of the digital radiograph of the middle phalanx of the third finger (MP3) in skeletal maturity assessment. Fifty children (24 girls and 26 boys) belonging to the circumpubertal age-group were selected for the study. Two radiographs - lateral cephalogram and digital radiograph of the MP3 region - were taken in each child. Age assessment was based on the changes in shape of the cervical vertebrae and the epiphysis of the middle phalanx of the third finger of the left hand. The radiographs were assessed by three examiners. The inter- and intraexaminer variability were determined by the Wilcoxon rank sign test and the Kruskal-Wallis test and were found to be nonsignificant. Examiner 3 showed the best intraexaminer agreement and was selected to evaluate the radiographs for the entire study. The correlation determined between the MP3 stages and cervical vertebrae maturity index (CVMI) stages, the peak-wise distribution of the MP3 stages, and the correlation between the MP3 stages and the chronological age were found to be highly significant. Digital radiograph of the MP3 region is definitely a simple, reliable, cost-effective, and time-saving technique for the assessment of skeletal maturity.

  4. One-stage hip reconstruction in children with cerebral palsy: long-term results at skeletal maturity.

    Science.gov (United States)

    Mallet, Cindy; Ilharreborde, B; Presedo, A; Khairouni, A; Mazda, K; Penneçot, G F

    2014-05-01

    Hip subluxation is common in children with cerebral palsy (CP). Surgery is indicated in case of pain or progressive increase of Reimers index on radiographs. Peri-iliac osteotomy combined with femoral osteotomy is one of the numerous operative techniques available, but results at skeletal maturity remain unclear. The purpose of this radiological study was to report the long-term results of this procedure. Twenty hips in 20 children were retrospectively evaluated at skeletal maturity. Mean age at surgery was 8.1 years and follow-up averaged 9.1 years. All patients underwent Dega acetabuloplasty, soft-tissue release and femoral-shortening varus derotation osteotomy without open reduction. Reimers index, acetabular angle (AA) and neck-shaft angle (NSA) were compared on preoperative, postoperative and latest follow-up radiographs. Dega osteotomy significantly improved the AA and the correction remained stable at maturity. The NSA significantly decreased postoperatively (153°-115°), but recurrence of the valgus deformity (130°) of the proximal femur was observed at maturity. Consequently, Reimers index followed the same evolution. No case of osteonecrosis was reported but one hip dislocated and one subluxated during follow-up. Progressive recurrence of the valgus deformity of the proximal femur, attributable to adductors spasticity and gluteus medius weakness, led to a significant increase in the Reimers index. However, hip coverage remained >70 % at maturity in 90 % of the hips. This one-stage procedure without hip dislocation efficaciously corrected acetabulum dysplasia and successfully treated neurological hips in CP patients. retrospective study.

  5. New software for cervical vertebral geometry assessment and its relationship to skeletal maturation--a pilot study.

    Science.gov (United States)

    Santiago, R C; Cunha, A R; Júnior, G C; Fernandes, N; Campos, M J S; Costa, L F M; Vitral, R W F; Bolognese, A M

    2014-01-01

    In the present study, we developed new software for quantitative analysis of cervical vertebrae maturation, and we evaluated its applicability through a multinomial logistic regression model (MLRM). Digitized images of the bodies of the second (C2), third (C3) and fourth (C4) cervical vertebrae were analysed in cephalometric radiographs of 236 subjects (116 boys and 120 girls) by using a software developed for digitized vertebrae analysis. The sample was initially distributed into 11 categories according to the Fishman's skeletal maturity indicators and were then grouped into four stages for quantitative cervical maturational changes (QCMC) analysis (QCMC I, II, III and IV). Seven variables of interest were measured and analysed to identify morphologic alterations of the vertebral bodies in each QCMC category. Statistically significant differences (p cervical vertebrae maturation categories was constructed by taking into account gender, chronological age and four variables determined by digitized vertebrae analysis (Ang_C3, MP_C3, MP_C4 and SP_C4). The MLRM presented a predictability of 81.4%. The weighted κ test showed almost perfect agreement (κ = 0.832) between the categories defined initially by the method of Fishman and those allocated by the MLRM. Significant alterations in the morphologies of the C2, C3 and C4 vertebral bodies that were analysed through the digitized vertebrae analysis software occur during the different stages of skeletal maturation. The model that combines the four parameters measured on the vertebral bodies, the age and the gender showed an excellent prediction.

  6. Correlation between Dental Maturity by Demirjian Method and Skeletal Maturity by Cervical Vertebral Maturity Method using Panoramic Radiograph and Lateral Cephalogram

    Directory of Open Access Journals (Sweden)

    Madhusudhanan Mallika Mini

    2017-01-01

    Full Text Available Introduction: Radiographs are effective tools in assessing the stages of bone maturation in dentistry. The cervical vertebral maturation method is a proven effective tool in assessing the adolescent growth spurt than hand-wrist radiographs in an individual. Assessment of dental calcification stages are a reliable method for determining dental maturity. Panoramic imaging can be used as the primary imaging modality for assessing maturity if a correlation can be found out between tooth calcification stages and cervical vertebral maturation stages. This study was conducted to determine the correlation between dental maturity stage and cervical vertebral maturity stage and to estimate predictor variables for cervical vertebral maturation stages (CVMS stratified by gender in a tertiary hospital setting. Materials and Methods: A descriptive study was conducted among patients accessing orthodontic care in radiology outpatient clinic, Oral Medicine and Radiology department, Government Dental College Thiruvananthapuram for a period of 15 months. Participants were selected between the ages of 8 and 16 years. Panoramic radiographs and lateral cephalograms were used to determine dental maturity stages using Demirjian method and CVMS using Bacetti and Franchi method, respectively. Results: One hundred patients (males = 46, females = 54 were included in the study; the spearman rank order correlation revealed significant relationship. The correlation ranged from 0.61 to 0.74 for females and 0.48 to 0.51 for males. Second premolar showed highest correlation and canine the lowest for both females and males. Stage G of mandibular second premolar signifies the pubertal growth period in this study population. By ordinal regression model, G stage of second premolar was found to be a significant predictor in males and stage H followed by G and F in females for the age group of 12–14 years. Conclusion: Dental maturation stages were significantly correlated with CVMS

  7. Application of different measures of skeletal maturity in initiating weaning from a brace for scoliosis: two case reports

    Directory of Open Access Journals (Sweden)

    Rivett LouAnn

    2009-04-01

    Full Text Available Abstract Introduction Various measures of skeletal maturity are used to initiate weaning from a brace in patients suffering from idiopathic scoliosis, resulting in different outcomes. We present two cases with double major curves, treated with the Rigo System Cheneau brace, and weaned using different criteria. Case presentation Case 1 was a South African, Caucasian girl who was initially treated with a brace at 14.75 years and who began weaning at 16.25 years on the basis of the Greulich and Pyle Index. She was out of her brace in 6 months, at least 11 months before reaching skeletal maturity as shown by the Risser Sign. Case 2 was a South African, Caucasian girl, initially treated with a brace at 14.25 years and who began the weaning process at 17.67 years on the basis of skeletal maturity according to the Risser Sign and static height for a period of 6 months. She was out of the brace 12 months later. In Case 1, the thoracic Cobb angle progressed during weaning and scoliometer readings deteriorated. The iliac apophysis fused 11 months after the wrist. In Case 2, the therapeutic gains made during the period of bracing were maintained during weaning, that is the improvement in the lumbar Cobb angle was maintained until the brace was removed, and scoliometer readings improved. The iliac apophysis fused 8.5 months after the wrist. Conclusions In patients with idiopathic scoliosis, it would seem to be more appropriate to base the timing of weaning on the Risser Sign and static height measurements rather than on traditional methods such as the Greulich and Pyle Index.

  8. Unusual facies, arthrogryposis, advanced skeletal maturation and unique bone changes. A new congenital malformation syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Jequier, S.; Kozlowski, K.

    1987-07-01

    Two strikingly similar infant siblings showed the following pattern of anomalies: unusual cranio-facial appearance, arthrogryposis, advanced bone age of the hips and unique skeletal X-ray abnormalities. They represent a previously unrecognised, fatal malformation syndrome.

  9. Validity of the assessment method of skeletal maturation by cervical vertebrae: a systematic review and meta-analysis

    Science.gov (United States)

    Bittencourt, M A V; Paranhos, L R

    2015-01-01

    Objectives: To perform a systematic review with meta-analysis to answer the question: is the cervical vertebrae maturation index (CVMI) effective to replace hand–wrist radiograph (gold standard) in determining the pubertal growth spurt in patients undergoing bone growth? Methods: A search in three databases was performed, in which studies were selected that compared one of the two main assessment methods for cervical vertebrae (Hassel B, Farman AG. Skeletal maturation evaluation using cervical vertebrae. Am J Orthod Dentofacial Orthop 1995; 107: 58–66, or Baccetti T, Franchi L, McNamara JA Jr. An improved version of the cervical vertebral maturation (CVM) method for the assessment of mandibular growth. Angle Orthod 2002; 72: 316–23) to a carpal assessment method. The main methodological data from each of the texts were collected and tabulated after. Later, the meta-analysis of the correlation coefficients obtained was performed. Results: 19 articles were selected from an initial 206 articles collected. Regardless of the method used, the results of the meta-analysis showed that every article selected presented a positive correlation between skeletal maturation assessment performed by cervical vertebrae and carpal methods, with discrepancy of values between genders indicating higher correlation for the female gender (0.925; 0.878) than for the male (0.879; 0.842). When the assessment was performed without gender separation, correlation was significant (0.592; 0.688) but lower in the cases when genders were separated. Conclusions: With the results of this meta-analysis, it is safe to affirm that both CVMIs used in the present study are reliable to replace the hand–wrist radiograph in predicting the pubertal growth spurt, considering that the highest values were found in female samples, especially in the method by Hassel and Farman. PMID:25521202

  10. Validity of the assessment method of skeletal maturation by cervical vertebrae: a systematic review and meta-analysis.

    Science.gov (United States)

    Cericato, G O; Bittencourt, M A V; Paranhos, L R

    2015-01-01

    To perform a systematic review with meta-analysis to answer the question: is the cervical vertebrae maturation index (CVMI) effective to replace hand-wrist radiograph (gold standard) in determining the pubertal growth spurt in patients undergoing bone growth? A search in three databases was performed, in which studies were selected that compared one of the two main assessment methods for cervical vertebrae (Hassel B, Farman AG. Skeletal maturation evaluation using cervical vertebrae. Am J Orthod Dentofacial Orthop 1995; 107: 58-66, or Baccetti T, Franchi L, McNamara JA Jr. An improved version of the cervical vertebral maturation (CVM) method for the assessment of mandibular growth. Angle Orthod 2002; 72: 316-23) to a carpal assessment method. The main methodological data from each of the texts were collected and tabulated after. Later, the meta-analysis of the correlation coefficients obtained was performed. 19 articles were selected from an initial 206 articles collected. Regardless of the method used, the results of the meta-analysis showed that every article selected presented a positive correlation between skeletal maturation assessment performed by cervical vertebrae and carpal methods, with discrepancy of values between genders indicating higher correlation for the female gender (0.925; 0.878) than for the male (0.879; 0.842). When the assessment was performed without gender separation, correlation was significant (0.592; 0.688) but lower in the cases when genders were separated. With the results of this meta-analysis, it is safe to affirm that both CVMIs used in the present study are reliable to replace the hand-wrist radiograph in predicting the pubertal growth spurt, considering that the highest values were found in female samples, especially in the method by Hassel and Farman.

  11. Role of dystroglycan in limiting contraction-induced injury to the sarcomeric cytoskeleton of mature skeletal muscle.

    Science.gov (United States)

    Rader, Erik P; Turk, Rolf; Willer, Tobias; Beltrán, Daniel; Inamori, Kei-Ichiro; Peterson, Taylor A; Engle, Jeffrey; Prouty, Sally; Matsumura, Kiichiro; Saito, Fumiaki; Anderson, Mary E; Campbell, Kevin P

    2016-09-27

    Dystroglycan (DG) is a highly expressed extracellular matrix receptor that is linked to the cytoskeleton in skeletal muscle. DG is critical for the function of skeletal muscle, and muscle with primary defects in the expression and/or function of DG throughout development has many pathological features and a severe muscular dystrophy phenotype. In addition, reduction in DG at the sarcolemma is a common feature in muscle biopsies from patients with various types of muscular dystrophy. However, the consequence of disrupting DG in mature muscle is not known. Here, we investigated muscles of transgenic mice several months after genetic knockdown of DG at maturity. In our study, an increase in susceptibility to contraction-induced injury was the first pathological feature observed after the levels of DG at the sarcolemma were reduced. The contraction-induced injury was not accompanied by increased necrosis, excitation-contraction uncoupling, or fragility of the sarcolemma. Rather, disruption of the sarcomeric cytoskeleton was evident as reduced passive tension and decreased titin immunostaining. These results reveal a role for DG in maintaining the stability of the sarcomeric cytoskeleton during contraction and provide mechanistic insight into the cause of the reduction in strength that occurs in muscular dystrophy after lengthening contractions.

  12. Caveolin-3 is associated with the T-tubules of mature skeletal muscle fibers

    DEFF Research Database (Denmark)

    Ralston, E; Ploug, Thorkil

    1999-01-01

    Caveolae are abundant in skeletal muscle and their coat contains a specific isoform of caveolin, caveolin-3. It has been suggested that during muscle development, caveolin-3 is associated with the T-tubules, but that in adult muscle it is found on the plasma membrane only. We have studied...... the distribution of caveolin-3 in single skeletal muscle fibers from adult rat soleus by confocal immunofluorescence and by immunogold electron microscopy. We found that caveolin-3 occurs at the highest density on the plasma membrane but is also present in the core of the fibers, at the I-band/A-band interface...

  13. Manipulation for the control of back pain and curve progression in patients with skeletally mature idiopathic scoliosis: two cases.

    Science.gov (United States)

    Tarola, G A

    1994-05-01

    This report of two cases illustrates the potential effect of chiropractic manipulative therapy on back pain and curve progression in the at-risk, skeletally mature patient with adolescent idiopathic scoliosis. Two patients suffering from lumbar scoliosis and chronic back pain. Both had scoliosis that had progressed after skeletal maturity. Diversified type chiropractic manipulative therapy was used palliatively for back pain relief in one case, and routinely 1-2 times per month in the other case. The manipulation was applied manually, with the patients in the prone and side-posture positions. Vertebral levels manipulated were identified as fixated/dysfunctional segments based on static and/or motion palpation. They were generally applied to areas above and/or below the curve apex. When applied at the apex, cavitation was more easily achieved when the direction of thrust was into the concave side. This was also tolerated better by the patient. No attempt was made to "straighten the curve" by thrusting into the convex side. Gentle manual intersegmental mobilization, stretching and muscle massage techniques were also applied. The case treated palliatively had curve progression consistent with the literature over an 8-yr period. The case treated routinely did not. The procedure was effective in both cases for subjective relief of back pain. Diversified-type CMT has a favorable effect on acute back pain when used palliatively. The procedure may also have a favorable long term effect of preventing recurrence of back pain and on retarding curve progression when used routinely 1-2 times per month.

  14. Age prediction formulae from radiographic assessment of skeletal maturation at the knee in an Irish population.

    LENUS (Irish Health Repository)

    O'Connor, Jean E

    2014-01-01

    Age estimation in living subjects is primarily achieved through assessment of a hand-wrist radiograph and comparison with a standard reference atlas. Recently, maturation of other regions of the skeleton has also been assessed in an attempt to refine the age estimates. The current study presents a method to predict bone age directly from the knee in a modern Irish sample. Ten maturity indicators (A-J) at the knee were examined from radiographs of 221 subjects (137 males; 84 females). Each indicator was assigned a maturity score. Scores for indicators A-G, H-J and A-J, respectively, were totalled to provide a cumulative maturity score for change in morphology of the epiphyses (AG), epiphyseal union (HJ) and the combination of both (AJ). Linear regression equations to predict age from the maturity scores (AG, HJ, AJ) were constructed for males and females. For males, equation-AJ demonstrated the greatest predictive capability (R(2)=0.775) while for females equation-HJ had the strongest capacity for prediction (R(2)=0.815). When equation-AJ for males and equation-HJ for females were applied to the current sample, the predicted age of 90% of subjects was within ±1.5 years of actual age for male subjects and within +2.0 to -1.9 years of actual age for female subjects. The regression formulae and associated charts represent the most contemporary method of age prediction currently available for an Irish population, and provide a further technique which can contribute to a multifactorial approach to age estimation in non-adults.

  15. The Difference in Cervical Vertebral Skeletal Maturation between Cleft Lip/Palate and Non-Cleft Lip/Palate Orthodontic Patients

    Directory of Open Access Journals (Sweden)

    Waeil Batwa

    2018-01-01

    Full Text Available Objective. The aim was to evaluate differences in the cervical vertebral skeletal maturity of unilateral cleft lip and palate (UCLP and non-cleft lip/palate (non-CLP Saudi male orthodontic patients. Method. This cross-sectional multicenter study took place at the dental school, King Saud University and King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, between October 2014 and September 2015. The records of Saudi male orthodontic patients with UCLP n=69 were collected. Cervical vertebral maturation was assessed using their cephalometric radiographs. The records of 138 age-matched non-CLP Saudi male orthodontic patients served as controls. Results. There was a significant difference in skeletal maturity between the UCLP and non-CLP groups, as evident in the delayed skeletal development among the UCLP participants. Moreover, pubertal growth spurt onset was significantly earlier in the non-cleft participants in comparison with the UCLP participants p=0.009. Conclusions. There is delayed skeletal maturity among the UCLP Saudi male population in comparison with their non-CLP age-matched peers.

  16. The Difference in Cervical Vertebral Skeletal Maturation between Cleft Lip/Palate and Non-Cleft Lip/Palate Orthodontic Patients.

    Science.gov (United States)

    Batwa, Waeil; Almoammar, Khalid; Aljohar, Aziza; Alhussein, Abdullah; Almujel, Saad; Zawawi, Khalid H

    2018-01-01

    The aim was to evaluate differences in the cervical vertebral skeletal maturity of unilateral cleft lip and palate (UCLP) and non-cleft lip/palate (non-CLP) Saudi male orthodontic patients. This cross-sectional multicenter study took place at the dental school, King Saud University and King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, between October 2014 and September 2015. The records of Saudi male orthodontic patients with UCLP ( n = 69) were collected. Cervical vertebral maturation was assessed using their cephalometric radiographs. The records of 138 age-matched non-CLP Saudi male orthodontic patients served as controls. There was a significant difference in skeletal maturity between the UCLP and non-CLP groups, as evident in the delayed skeletal development among the UCLP participants. Moreover, pubertal growth spurt onset was significantly earlier in the non-cleft participants in comparison with the UCLP participants ( p = 0.009). There is delayed skeletal maturity among the UCLP Saudi male population in comparison with their non-CLP age-matched peers.

  17. Developmental steps of the human cervical spine: parameters for evaluation of skeletal maturation stages.

    Science.gov (United States)

    dos Santos, Marcos Fabio Henriques; de Lima, Rodrigo Lopes; De-Ary-Pires, Bernardo; Pires-Neto, Mário Ary; de Ary-Pires, Ricardo

    2010-06-01

    The central objective of this investigation was to focus on the development of the cervical spine observed by lateral cephalometric radiological images of children and adolescents (6-16 years old). A sample of 26 individuals (12 girls and 14 boys) was classified according to stages of cervical spine maturation in two subcategories: group I (initiation phase) and group II (acceleration phase). The morphology of the cervical spine was assessed by lateral cephalometric radiographs obtained in accordance with an innovative method for establishing a standardized head posture. A total of 29 linear variables and 5 angular variables were used to clarify the dimensions of the cervical vertebrae. The results suggest that a few measurements can be used as parameters of vertebral maturation both for males and females. The aforementioned measurements include the inferior depth of C2-C4, the inferior depth of C5, the anterior height of C4-C5, and the posterior height of C5. We propose original morphological parameters that may prove remarkably useful in the determination of bone maturational stages of the cervical spine in children and adolescents.

  18. Physical activity and biological maturation: a systematic review

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    Eliane Denise Araújo Bacil

    2015-03-01

    Full Text Available OBJECTIVE: To analyze the association between physical activity (PA and biological maturation in children and adolescents. DATA SOURCE: We performed a systematic review in April 2013 in the electronic databases of PubMed/MEDLINE, SportDiscus, Web of Science and LILACS without time restrictions. A total of 628 potentially relevant articles were identified and 10 met the inclusion criteria for this review: cross-sectional or longitudinal studies, published in Portuguese, English or Spanish, with schoolchildren aged 9-15 years old of both genders. DATA SYNTHESIS: Despite the heterogeneity of the studies, there was an inverse association between PA and biological maturation. PA decreases with increased biological and chronological age in both genders. Boys tend to be more physically active than girls; however, when controlling for biological age, the gender differences disappear. The association between PA and timing of maturation varies between the genders. Variation in the timing of biological maturation affects the tracking of PA in early adolescent girls. This review suggests that mediators (BMI, depression, low self-esteem, and concerns about body weight can explain the association between PA and biological maturation. CONCLUSIONS: There is an association between PA and biological maturation. PA decreases with increasing biological age with no differences between genders. As for the timing of biological maturation, this association varies between genders.

  19. Skeletal maturation, fundamental motor skills and motor performance in preschool children.

    Science.gov (United States)

    Freitas, D L; Lausen, B; Maia, J A; Gouveia, É R; Antunes, A M; Thomis, M; Lefevre, J; Malina, R M

    2018-06-01

    Relationships among skeletal age (SA), body size and fundamental motor skills (FMS) and motor performance were considered in 155 boys and 159 girls 3-6 years of age. Stature and body mass were measured. SA of the hand-wrist was assessed with the Tanner-Whitehouse II 20 bone method. The Test of Gross Motor Development, 2 nd edition (TGMD-2) and the Preschool Test Battery were used, respectively, to assess FMS and motor performance. Based on hierarchical regression analyses, the standardized residuals of SA on chronological age (SAsr) explained a maximum of 6.1% of the variance in FMS and motor performance in boys (ΔR 2 3 , range 0.0% to 6.1%) and a maximum of 20.4% of the variance in girls (ΔR 2 3 , range 0.0% to 20.4%) over that explained by body size and interactions of SAsr with body size (step 3). The interactions of the SAsr and stature and body mass (step 2) explained a maximum of 28.3% of the variance in boys (ΔR 2 2 , range 0.5% to 28.3%) and 16.7% of the variance in girls (ΔR 2 2 , range 0.7% to 16.7%) over that explained by body size alone. With the exception of balance, relationships among SAsr and FMS or motor performance differed between boys and girls. Overall, SA per se or interacting with body size had a relatively small influence in FMS and motor performance in children 3-6 years of age. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  20. Osteocalcin and serum insulin-like growth factor-1 as biochemical skeletal maturity indicators

    Directory of Open Access Journals (Sweden)

    Tulika Tripathi

    2017-10-01

    Full Text Available Abstract Background With change in concepts of growth determination methods, there is a surge in the measurement of biomarkers for appraisal of growth status. Osteocalcin is a bone-specific protein and was observed to parallel the normal growth curve. Hence, the present study was intended to assess the levels of serum osteocalcin and serum insulin-like growth factor-1 (IGF-1 and compare them with cervical vertebral maturation index (CVMI stages. Methods The cross-sectional study was performed on 150 subjects (75 males and 75 females in the age group of 8–20 years and segregated into six CVMI stages. Serum osteocalcin and IGF-1 were estimated by ELISA. Mann-Whitney U test was used to compare the mean ranks of serum osteocalcin and serum IGF-1 with different CVMI stages. Spearman correlation was performed to find association between serum osteocalcin and serum IGF-1 across six CVMI stages. Results Peak serum IGF-1 levels were obtained at CVMI stages 4 and 3 for males and females, respectively, with insignificant difference between stages 3 and 4 in females. Peak serum osteocalcin levels were found at stage 5 and 3 for males and females with insignificant difference from other stages except stages 5 and 6 in males. A statistically significant correlation was seen between serum IGF-1 and serum osteocalcin across six CVMI stages (P < 0.01. Conclusions Osteocalcin followed IGF-1 across all CVMI stages but showed insignificant interstage differences.

  1. Effectiveness of Chêneau brace treatment for idiopathic scoliosis: prospective study in 79 patients followed to skeletal maturity

    Directory of Open Access Journals (Sweden)

    Kotwicki Tomasz

    2011-01-01

    Full Text Available Abstract Background Progressive idiopathic scoliosis can negatively influence the development and functioning of 2-3% of adolescents, with health consequences and economic costs, placing the disease in the centre of interest of the developmental medicine. The aim of this study was to evaluate the effectiveness of Chêneau brace in the management of idiopathic scoliosis. Methods A prospective observational study according to SOSORT and SRS recommendations comprised 79 patients (58 girls and 21 boys with progressive idiopathic scoliosis, treated with Chêneau brace and physiotherapy, with initial Cobb angle between 20 and 45 degrees, no previous brace treatment, Risser 4 or more at the final evaluation and minimum one year follow-up after weaning the brace. Achieving 50° of Cobb angle was considered surgical recommendation. Results At follow-up 20 patients (25.3% improved, 18 patients (22.8% were stable, 31 patients (39.2% progressed below 50 degrees and 10 patients (12.7% progressed beyond 50 degrees (2 of these 10 patients progressed beyond 60 degrees. Progression concerned the younger and less skeletally mature patients. Conclusion Conservative treatment with Chêneau orthosis and physiotherapy was effective in halting scoliosis progression in 48.1% of patients. The results of this study suggest that bracing is effective in reducing the incidence of surgery in comparison with natural history.

  2. Quantitative skeletal maturation estimation using cone-beam computed tomography-generated cervical vertebral images: a pilot study in 5- to 18-year-old Japanese children.

    Science.gov (United States)

    Byun, Bo-Ram; Kim, Yong-Il; Yamaguchi, Tetsutaro; Maki, Koutaro; Ko, Ching-Chang; Hwang, Dea-Seok; Park, Soo-Byung; Son, Woo-Sung

    2015-11-01

    The purpose of this study was to establish multivariable regression models for the estimation of skeletal maturation status in Japanese boys and girls using the cone-beam computed tomography (CBCT)-based cervical vertebral maturation (CVM) assessment method and hand-wrist radiography. The analyzed sample consisted of hand-wrist radiographs and CBCT images from 47 boys and 57 girls. To quantitatively evaluate the correlation between the skeletal maturation status and measurement ratios, a CBCT-based CVM assessment method was applied to the second, third, and fourth cervical vertebrae. Pearson's correlation coefficient analysis and multivariable regression analysis were used to determine the ratios for each of the cervical vertebrae (p maturation status according to the CBCT-based quantitative cervical vertebral maturation (QCVM) assessment was 5.90 + 99.11 × AH3/W3 - 14.88 × (OH2 + AH2)/W2 + 13.24 × D2; for the Japanese girls, it was 41.39 + 59.52 × AH3/W3 - 15.88 × (OH2 + PH2)/W2 + 10.93 × D2. The CBCT-generated CVM images proved very useful to the definition of the cervical vertebral body and the odontoid process. The newly developed CBCT-based QCVM assessment method showed a high correlation between the derived ratios from the second cervical vertebral body and odontoid process. There are high correlations between the skeletal maturation status and the ratios of the second cervical vertebra based on the remnant of dentocentral synchondrosis.

  3. Progressive skeletal benefits of physical activity when young as assessed at the midshaft humerus in male baseball players.

    Science.gov (United States)

    Warden, S J; Weatherholt, A M; Gudeman, A S; Mitchell, D C; Thompson, W R; Fuchs, R K

    2017-07-01

    Physical activity benefits the skeleton, but there is contrasting evidence regarding whether benefits differ at different stages of growth. The current study demonstrates that physical activity should be encouraged at the earliest age possible and be continued into early adulthood to gain most skeletal benefits. The current study explored physical activity-induced bone adaptation at different stages of somatic maturity by comparing side-to-side differences in midshaft humerus properties between male throwing athletes and controls. Throwers present an internally controlled model, while inclusion of control subjects removes normal arm dominance influences. Throwing athletes (n = 90) and controls (n = 51) were categorized into maturity groups (pre, peri, post-early, post-mid, and post-late) based on estimated years from peak height velocity (10 years). Side-to-side percent differences in midshaft humerus cortical volumetric bone mineral density (Ct.vBMD) and bone mineral content (Ct.BMC); total (Tt.Ar), medullary (Me.Ar), and cortical (Ct.Ar) areas; average cortical thickness (Ct.Th); and polar Strength Strain Index (SSI P ) were assessed. Significant interactions between physical activity and maturity on side-to-side differences in Ct.BMC, Tt.Ar, Ct.Ar, Me.Ar, Ct.Th, and SSI P resulted from the following: (1) greater throwing-to-nonthrowing arm differences than dominant-to-nondominant arm differences in controls (all p benefits beginning prior to and continuing beyond somatic maturation and that a longer duration of exposure to physical activity has cumulative skeletal benefits. Thus, physical activity should be encouraged at the earliest age possible and be continued into early adulthood to optimize skeletal benefits.

  4. Management of osteonecrosis of the femoral head in children with sickle cell disease: results of conservative and operative treatments at skeletal maturity

    Science.gov (United States)

    Mallet, C.; Abitan, A.; Vidal, C.; Holvoet, L.; Mazda, K.; Simon, A.-L.; Ilharreborde, B.

    2018-01-01

    Abstract Purpose Sickle cell disease (SCD) is the most common cause of femoral head osteonecrosis (ONFH) during childhood with an overall prevalence of 10%. In children, spontaneous revascularization can occur, as in Legg-Calve-Perthes disease. Consequently, the aim of treatment is to restore proper hip containment to prevent joint arthritis. This is the first study reporting long-term results at skeletal maturity of non-operative and surgical treatments for ONFH in SCD children. Methods All children with ONFH due to SCD were retrospectively reviewed. At initial evaluation, extension of osteonecrosis was radiographically defined using Catterall, lateral pillar Herring and Ficat classifications. Subluxation of the femoral head with Reimers migration index > 30% required surgical treatment including femoral varus osteotomy and/or pelvic osteotomies. Conservative treatment including non-weight bearing and physiotherapy was performed in the remaining cases. Outcomes were assessed at skeletal maturity using the Harris Hip Score (HHS) and the Stulberg classification. Total hip arthroplasty and Stulberg 5 were defined as failures. Results A total of 25 hips in 17 patients were included (mean follow-up 7.5 years SD 3.4). Mean age at diagnosis was 11.4 years SD 2.9. In all, 15 hips (60%) were classified Catterall 3 and 4 and Herring B and C. A total of 13 patients (52%) underwent surgical treatment. At skeletal maturity, mean HHS was good (81 SD 17), 12 hips (48%) were classified Stulberg 1 and 2, seven hips (28%) were classified Stulberg 3 and 4. Conclusion Both treatments led to good functional results with 75% of congruent hips at skeletal maturity. Level of Evidence IV PMID:29456754

  5. Management of osteonecrosis of the femoral head in children with sickle cell disease: results of conservative and operative treatments at skeletal maturity.

    Science.gov (United States)

    Mallet, C; Abitan, A; Vidal, C; Holvoet, L; Mazda, K; Simon, A-L; Ilharreborde, B

    2018-02-01

    Sickle cell disease (SCD) is the most common cause of femoral head osteonecrosis (ONFH) during childhood with an overall prevalence of 10%. In children, spontaneous revascularization can occur, as in Legg-Calve-Perthes disease. Consequently, the aim of treatment is to restore proper hip containment to prevent joint arthritis. This is the first study reporting long-term results at skeletal maturity of non-operative and surgical treatments for ONFH in SCD children. All children with ONFH due to SCD were retrospectively reviewed. At initial evaluation, extension of osteonecrosis was radiographically defined using Catterall, lateral pillar Herring and Ficat classifications. Subluxation of the femoral head with Reimers migration index > 30% required surgical treatment including femoral varus osteotomy and/or pelvic osteotomies. Conservative treatment including non-weight bearing and physiotherapy was performed in the remaining cases. Outcomes were assessed at skeletal maturity using the Harris Hip Score (HHS) and the Stulberg classification. Total hip arthroplasty and Stulberg 5 were defined as failures. A total of 25 hips in 17 patients were included (mean follow-up 7.5 years SD 3.4). Mean age at diagnosis was 11.4 years SD 2.9. In all, 15 hips (60%) were classified Catterall 3 and 4 and Herring B and C. A total of 13 patients (52%) underwent surgical treatment. At skeletal maturity, mean HHS was good (81 SD 17), 12 hips (48%) were classified Stulberg 1 and 2, seven hips (28%) were classified Stulberg 3 and 4. Both treatments led to good functional results with 75% of congruent hips at skeletal maturity. IV.

  6. Management of osteonecrosis of the femoral head in children with sickle cell disease: results of conservative and operative treatments at skeletal maturity

    OpenAIRE

    Mallet, C.; Abitan, A.; Vidal, C.; Holvoet, L.; Mazda, K.; Simon, A.-L.; Ilharreborde, B.

    2018-01-01

    Abstract Purpose Sickle cell disease (SCD) is the most common cause of femoral head osteonecrosis (ONFH) during childhood with an overall prevalence of 10%. In children, spontaneous revascularization can occur, as in Legg-Calve-Perthes disease. Consequently, the aim of treatment is to restore proper hip containment to prevent joint arthritis. This is the first study reporting long-term results at skeletal maturity of non-operative and surgical treatments for ONFH in SCD children. Methods All ...

  7. Thermal mud maturation: organic matter and biological activity.

    Science.gov (United States)

    Centini, M; Tredici, M R; Biondi, N; Buonocore, A; Maffei Facino, R; Anselmi, C

    2015-06-01

    Many of the therapeutic and cosmetic treatments offered in spas are centred on mud therapy, to moisturize the skin and prevent skin ageing and rheumatic diseases. Thermal mud is a complex matrix composed of organic and inorganic elements which contribute to its functions. It is a natural product derived from the long mixing of clay and thermal water. During its maturation, organic substances are provided by the microalgae, which develop characteristic of the composition of thermal water. The aim of this study was to identify methods for introducing objective parameters as a basis for characterizing thermal mud and assessing its efficacy. Samples of thermal mud were collected at the Saturnia spa, where there are several sulphureous pools. The maturation of the mud was evaluated by organic component determination using extractive methods and chromatographic analysis (HPLC, GC-MS, SPME). We also studied the radical scavenging activity of mud samples at different stages of maturation, in a homogeneous phase, using several tests (DPPH, ORAC, ABTS). We identified several classes of compounds: saturated and unsaturated fatty acids, hydroxyl acids, dicarboxylic acids, ketoacids, alcohols and others. SPME analysis showed the presence of various hydrocarbons compounds (C(11) -C(17)) and long-chain alcohols (C(12) -C(16)). Six or seven months seemed appropriate to complete the process of maturation, and the main effect of maturation time was the increase of lipids. Six-month mud showed the highest activity. The hydrophilic extract was more active than the lipophilic extract. The results indicate that maturation of thermal mud can be followed on the basis of the changes in its organic composition and antioxidant properties along the time. They also highlight the need to develop reference standards for thermal muds in relation to assess their use for therapeutic and cosmetic purposes. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  8. Bone mineral density, chemical composition and biomechanical properties of the tibia of female rats exposed to cadmium since weaning up to skeletal maturity.

    Science.gov (United States)

    Brzóska, M M; Majewska, K; Moniuszko-Jakoniuk, J

    2005-10-01

    The influence of exposure to cadmium (Cd) during skeletal development on the risk of bone fractures at the stage of skeletal maturity was investigated on a female rat model of human exposure. The tibias of rats treated with 1, 5 or 50 mg Cd/l in drinking water for 3, 6, 9 and 12 months (since weaning) were used. The exposure to Cd dose- and time-dependently influenced the tibia bone mineral density (BMD) and chemical composition. In skeletally matured animals, at each level of the exposure to Cd, the BMD at the whole tibia and its diaphysis as well as the percentage of minerals content in the bone, including the content of zinc, copper and iron, were decreased compared to control. Moreover, in the 50 mg Cd/l group, the percentage of organic components content increased. The Cd-induced changes, at all levels of exposure, resulted in weakening in the yield strength and fracture strength of the tibia (a three-point bending test of the diaphysis and compression test with vertical loading) of the skeletally matured females. A very important and clinically useful finding of this study is that a decrease (even by several percent) in the tibia BMD results in weakness in the bone biomechanical properties and that the BMD may predict the risk of its fracture at the exposure to Cd. Moreover, the results together with our previous findings seem to suggest that tibia, due to higher vulnerability of its diaphysis, compared to the femoral diaphysis, to damage by Cd may be more useful than femur to investigate the effect of Cd on the cortical bone. The present study revealed that a low exposure to Cd (1 mg Cd/l), corresponding to low human environmental exposure, during the skeletal development affects the tibia mineral status leading to weakening in its mechanical properties at the skeletal maturity. The findings allow for the conclusion that environmental exposure to Cd during childhood and adolescence may enhance the risk of low BMD and fractures at adulthood.

  9. Three-dimensional assessment of curvature, torsion, and canal flare index of the humerus of skeletally mature nonchondrodystrophic dogs.

    Science.gov (United States)

    Smith, Emily J; Marcellin-Little, Denis J; Harrysson, Ola L A; Griffith, Emily H

    2017-10-01

    OBJECTIVE To assess 3-D geometry of the humerus of dogs and determine whether the craniocaudal canal flare index (CFI) is associated with specific geometric features. SAMPLE CT images (n = 40) and radiographs (38) for 2 groups of skeletally mature nonchondrodystrophic dogs. PROCEDURES General dimensions (length, CFI, cortical thickness, and humeral head offset), curvature (shaft, humeral head, and glenoid cavity), version (humeral head and greater tubercle), and torsion were evaluated on CT images. Dogs were allocated into 3 groups on the basis of the craniocaudal CFI, and results were compared among these 3 groups. The CT measurements were compared with radiographic measurements obtained for another group of dogs. RESULTS Mean ± SD humeral head version was -75.9 ± 9.6° (range, -100.7° to -59.4°). Mean mechanical lateral distal humeral angle, mechanical caudal proximal humeral angle, and mechanical cranial distal humeral angle were 89.5 ± 3.5°, 50.2 ± 4.5°, and 72.9 ± 7.8°, respectively, and did not differ from corresponding radiographic measurements. Mean humeral curvature was 20.4 ± 4.4° (range, 9.6° to 30.5°). Mean craniocaudal CFI was 1.74 ± 0.18 (range, 1.37 to 2.10). Dogs with a high craniocaudal CFI had thicker cranial and medial cortices than dogs with a low craniocaudal CFI. Increased body weight was associated with a lower craniocaudal CFI. Radiographic and CT measurements of craniocaudal CFI and curvature differed significantly. CONCLUSIONS AND CLINICAL RELEVANCE CT-based 3-D reconstructions allowed the assessment of shaft angulation, torsion, and CFI. Radiographic and CT measurements of shaft curvature and CFI may differ.

  10. Performance of a Deep-Learning Neural Network Model in Assessing Skeletal Maturity on Pediatric Hand Radiographs.

    Science.gov (United States)

    Larson, David B; Chen, Matthew C; Lungren, Matthew P; Halabi, Safwan S; Stence, Nicholas V; Langlotz, Curtis P

    2018-04-01

    Purpose To compare the performance of a deep-learning bone age assessment model based on hand radiographs with that of expert radiologists and that of existing automated models. Materials and Methods The institutional review board approved the study. A total of 14 036 clinical hand radiographs and corresponding reports were obtained from two children's hospitals to train and validate the model. For the first test set, composed of 200 examinations, the mean of bone age estimates from the clinical report and three additional human reviewers was used as the reference standard. Overall model performance was assessed by comparing the root mean square (RMS) and mean absolute difference (MAD) between the model estimates and the reference standard bone ages. Ninety-five percent limits of agreement were calculated in a pairwise fashion for all reviewers and the model. The RMS of a second test set composed of 913 examinations from the publicly available Digital Hand Atlas was compared with published reports of an existing automated model. Results The mean difference between bone age estimates of the model and of the reviewers was 0 years, with a mean RMS and MAD of 0.63 and 0.50 years, respectively. The estimates of the model, the clinical report, and the three reviewers were within the 95% limits of agreement. RMS for the Digital Hand Atlas data set was 0.73 years, compared with 0.61 years of a previously reported model. Conclusion A deep-learning convolutional neural network model can estimate skeletal maturity with accuracy similar to that of an expert radiologist and to that of existing automated models. © RSNA, 2017 An earlier incorrect version of this article appeared online. This article was corrected on January 19, 2018.

  11. Measuring agreement between cervical vertebrae and hand-wrist maturation in determining skeletal age: reassessing the theory in patients with short stature.

    Science.gov (United States)

    Danaei, Shahla Momeni; Karamifar, Amirali; Sardarian, Ahmadreza; Shahidi, Shoaleh; Karamifar, Hamdollah; Alipour, Abbas; Ghodsi Boushehri, Sahar

    2014-09-01

    The objective of this study was to determine the degree of agreement between hand-wrist radiography and cervical vertebral maturation analysis in patients diagnosed with short stature. A cross-sectional study was designed; 178 patients (90 girls, 88 boys) diagnosed with short stature and seeking treatment were selected. The patients were divided into 2 groups (76 with familial short stature, 102 with nonfamilial short stature). Hand-wrist and lateral cephalometric radiographs were obtained from the patients. The hand-wrist radiographs were analyzed using the Fishman method, and the lateral cephalometric views were categorized according to the method of Hassel and Farman. The degree of agreement between the 2 methods of predicting skeletal maturation was measured by calculating the contingency coefficient and the weighted kappa statistic. A high degree of agreement was observed between the 2 methods of analyzing skeletal maturation. It was also observed that agreement was higher in girls in the familial short-stature group, whereas boys had higher agreement in the nonfamilial short-stature group. Cervical vertebral maturation can be a valuable substitute for hand-wrist radiography in patients with short stature. Copyright © 2014 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  12. An evaluation on time status of functional orthopedic treatment in class II skeletal patients with cervical vertebrae maturation stage (CVMS index

    Directory of Open Access Journals (Sweden)

    Dalili Z.

    2004-08-01

    Full Text Available Statement of Problem: Considerable response to functional orthopedic appliances treatment in class II skeletal patients occurs during pubertal growth spurt. Therefore, it seems necessary to investigate indices indicating mandibular growth pattern. It has been proved that analyzing cervical vertebral maturation stage is a more valid index than that of hand wrist. Purpose: The aim of this study was to evaluate the time status of functional orthopedic treatment in class II skeletal patients using CVMS index. Materials and Methods: In this descriptive-inferential study, lateral cephalometric radiographs of 153 class II skeletal patients with mandibular deficiency, before treatment, were studied by an oral and maxillofacial radiologist using the index of cervical vertebral maturation stage (CVMS and were categorized in three phases: CVMS I (desirable phase of treatment, CVMS II (ideal phase, and CVMS III (undesirable phase of treatment. Results: Statistical analysis ranked the prevalence of treatment phases as: 41.8% in desirable phase (CVMS I, 28.1% in ideal phase (CVMA II and 30% in undesirable phase (CVMS III. No significant differences were found between the three phases using Chi-square analysis. Time status of functional orthopedic treatment was also evaluated based on age and sex. The results showed significant differences between two sexes (P=0.032. Conclusion: The present study suggests the analysis of CVMS index, along with clinical criteria, in the determination of an ideal time for functional orthopedic treatment to prevent patients’ exhaustion during treatment Period.

  13. Activation of dormant ovarian follicles to generate mature eggs.

    Science.gov (United States)

    Li, Jing; Kawamura, Kazuhiro; Cheng, Yuan; Liu, Shuang; Klein, Cynthia; Liu, Shu; Duan, En-Kui; Hsueh, Aaron J W

    2010-06-01

    Although multiple follicles are present in mammalian ovaries, most of them remain dormant for years or decades. During reproductive life, some follicles are activated for development. Genetically modified mouse models with oocyte-specific deletion of genes in the PTEN-PI3K-Akt-Foxo3 pathway exhibited premature activation of all dormant follicles. Using an inhibitor of the Phosphatase with TENsin homology deleted in chromosome 10 (PTEN) phosphatase and a PI3K activating peptide, we found that short-term treatment of neonatal mouse ovaries increased nuclear exclusion of Foxo3 in primordial oocytes. After transplantation under kidney capsules of ovariectomized hosts, treated follicles developed to the preovulatory stage with mature eggs displaying normal epigenetic changes of imprinted genes. After in vitro fertilization and embryo transfer, healthy progeny with proven fertility were delivered. Human ovarian cortical fragments from cancer patients were also treated with the PTEN inhibitor. After xeno-transplantation to immune-deficient mice for 6 months, primordial follicles developed to the preovulatory stage with oocytes capable of undergoing nuclear maturation. Major differences between male and female mammals are unlimited number of sperm and paucity of mature oocytes. Thus, short-term in vitro activation of dormant ovarian follicles after stimulation of the PI3K-Akt pathway allows the generation of a large supply of mature female germ cells for future treatment of infertile women with a diminishing ovarian reserve and for cancer patients with cryo-preserved ovaries. Generation of a large number of human oocytes also facilitates future derivation of embryonic stem cells for regenerative medicine.

  14. The Sandia MEMS passive shock sensor : FY07 maturation activities.

    Energy Technology Data Exchange (ETDEWEB)

    Houston, Jack E.; Blecke, Jill; Mitchell, John Anthony; Wittwer, Jonathan W.; Crowson, Douglas A.; Clemens, Rebecca C.; Walraven, Jeremy Allen; Epp, David S.; Baker, Michael Sean

    2008-08-01

    This report describes activities conducted in FY07 to mature the MEMS passive shock sensor. The first chapter of the report provides motivation and background on activities that are described in detail in later chapters. The second chapter discusses concepts that are important for integrating the MEMS passive shock sensor into a system. Following these two introductory chapters, the report details modeling and design efforts, packaging, failure analysis and testing and validation. At the end of FY07, the MEMS passive shock sensor was at TRL 4.

  15. Impaired glycogen synthase activity and mitochondrial dysfunction in skeletal muscle

    DEFF Research Database (Denmark)

    Højlund, Kurt; Beck-Nielsen, Henning

    2006-01-01

    Insulin resistance in skeletal muscle is a major hallmark of type 2 diabetes and an early detectable abnormality in the development of this disease. The cellular mechanisms of insulin resistance include impaired insulin-mediated muscle glycogen synthesis and increased intramyocellular lipid content......, whereas impaired insulin activation of muscle glycogen synthase represents a consistent, molecular defect found in both type 2 diabetic and high-risk individuals. Despite several studies of the insulin signaling pathway believed to mediate dephosphorylation and hence activation of glycogen synthase......, the molecular mechanisms responsible for this defect remain unknown. Recently, the use of phospho-specific antibodies in human diabetic muscle has revealed hyperphosphorylation of glycogen synthase at sites not regulated by the classical insulin signaling pathway. In addition, novel approaches such as gene...

  16. Activation of the skeletal alpha-actin promoter during muscle regeneration.

    Science.gov (United States)

    Marsh, D R; Carson, J A; Stewart, L N; Booth, F W

    1998-11-01

    Little is known concerning promoter regulation of genes in regenerating skeletal muscles. In young rats, recovery of muscle mass and protein content is complete within 21 days. During the initial 5-10 days of regeneration, mRNA abundance for IGF-I, myogenin and MyoD have been shown to be dramatically increased. The skeletal alpha-actin promoter contains E box and serum response element (SRE) regulatory regions which are directly or indirectly activated by myogenin (or MyoD) and IGF-I proteins, respectively. We hypothesized that the skeletal alpha-actin promoter activity would increase during muscle regeneration, and that this induction would occur before muscle protein content returned to normal. Total protein content and the percentage content of skeletal alpha-actin protein was diminished at 4 and 8 days and re-accumulation had largely occurred by 16 days post-bupivacaine injection. Skeletal alpha-actin mRNA per whole muscle was decreased at day 8, and thereafter returned to control values. During regeneration at day 8, luciferase activity (a reporter of promoter activity) directed by -424 skeletal alpha-actin and -99 skeletal alpha-actin promoter constructs was increased by 700% and 250% respectively; however, at day 16, skeletal alpha-actin promoter activities were similar to control values. Thus, initial activation of the skeletal alpha-actin promoter is associated with regeneration of skeletal muscle, despite not being sustained during the later stages of regrowth. The proximal SRE of the skeletal alpha-actin promoter was not sufficient to confer a regeneration-induced promoter activation, despite increased serum response factor protein binding to this regulatory element in electrophoretic mobility shift assays. Skeletal alpha-actin promoter induction during regeneration is due to a combination of regulatory elements, at least including the SRE and E box.

  17. Changes in contractile activation characteristics of rat fast and slow skeletal muscle fibres during regeneration.

    Science.gov (United States)

    Gregorevic, Paul; Plant, David R; Stupka, Nicole; Lynch, Gordon S

    2004-07-15

    Damaged skeletal muscle fibres are replaced with new contractile units via muscle regeneration. Regenerating muscle fibres synthesize functionally distinct isoforms of contractile and regulatory proteins but little is known of their functional properties during the regeneration process. An advantage of utilizing single muscle fibre preparations is that assessment of their function is based on the overall characteristics of the contractile apparatus and regulatory system and as such, these preparations are sensitive in revealing not only coarse, but also subtle functional differences between muscle fibres. We examined the Ca(2+)- and Sr(2+)-activated contractile characteristics of permeabilized fibres from rat fast-twitch (extensor digitorum longus) and slow-twitch (soleus) muscles at 7, 14 and 21 days following myotoxic injury, to test the hypothesis that fibres from regenerating fast and slow muscles have different functional characteristics to fibres from uninjured muscles. Regenerating muscle fibres had approximately 10% of the maximal force producing capacity (P(o)) of control (uninjured) fibres, and an altered sensitivity to Ca(2+) and Sr(2+) at 7 days post-injury. Increased force production and a shift in Ca(2+) sensitivity consistent with fibre maturation were observed during regeneration such that P(o) was restored to 36-45% of that in control fibres by 21 days, and sensitivity to Ca(2+) and Sr(2+) was similar to that of control (uninjured) fibres. The findings support the hypothesis that regenerating muscle fibres have different contractile activation characteristics compared with mature fibres, and that they adopt properties of mature fast- or slow-twitch muscle fibres in a progressive manner as the regeneration process is completed.

  18. Lower physical activity is associated with fat infiltration within skeletal muscle in young girls

    Science.gov (United States)

    Fat infiltration within skeletal muscle is strongly associated with obesity, type 2 diabetes mellitus, and metabolic syndrome. Lower physical activity may be a risk factor for greater fat infiltration within skeletal muscle, although whether lower physical activity is associated with fat infiltrati...

  19. Expression and Regulation of Corticotropin-Releasing Factor Receptor Type 2 beta in Developing and Mature Mouse Skeletal Muscle

    NARCIS (Netherlands)

    Kuperman, Yael; Issler, Orna; Vaughan, Joan; Bilezikjian, Louise; Vale, Wylie; Chen, Alon

    Corticotropin-releasing factor receptor type 2 (CRFR2) is highly expressed in skeletal muscle (SM) tissue where it is suggested to inhibit interactions between insulin signaling pathway components affecting whole-body glucose homeostasis. However, little is known about factors regulating SM CRFR2

  20. Acute sex hormone suppression reduces skeletal muscle sympathetic nerve activity.

    Science.gov (United States)

    Day, Danielle S; Gozansky, Wendolyn S; Bell, Christopher; Kohrt, Wendy M

    2011-10-01

    Comparisons of sympathetic nervous system activity (SNA) between young and older women have produced equivocal results, in part due to inadequate control for potential differences in sex hormone concentrations, age, and body composition. The aim of the present study was to determine the effect of a short-term reduction in sex hormones on tonic skeletal muscle sympathetic nerve activity (MSNA), an indirect measure of whole body SNA, using an experimental model of sex hormone deficiency in young women. We also assessed the independent effects of estradiol and progesterone add-back therapy on MSNA. MSNA was measured in 9 women (30±2 years; mean±SE) on three separate occasions: during the mid-luteal menstrual cycle phase, on the fifth day of gonadotropin-releasing hormone antagonist (GnRHant) administration, and after 5 days add-back of either estradiol (n=4) or progesterone (n=3) during continued GnRHant administration. In response to GnRHant, there were significant reductions in serum estradiol and progesterone (both psuppression attenuates MSNA and that this may be related to the suppression of progesterone rather than estradiol.

  1. Dendritic Cells Activate and Mature after Infection with Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Mamo Gezahagne

    2011-07-01

    Full Text Available Abstract Background Dendritic cells (DCs can take up an array of different antigens, including microorganisms which they can process and present more effectively than any other antigen presenting cell. However, whether the interaction between the human DC and Mycobacterium tuberculosis represents a defense mechanism by the invaded host, or helping the invader to evade the defense mechanism of the host is still not clearly understood. Findings To analyze the interactions between M. tuberculosis and immune cells, human peripheral blood monocyte-derived immature DCs were infected with M. tuberculosis H37Rv wild type strain and flow cytometry was used to analyse cell surface expression markers. The ability of the M. tuberculosis infected DC to induce T cell proliferation using 5 and 6-carboxyfluorescein diacetate succinimidyl ester (CFSE dilution technique was also investigated. DCs were found to internalize the mycobacteria and show dose dependent infection and necrosis with different multiplicity of infection. Flow cytometry analysis of cell surface expression markers CD40, CD54, CD80, CD83, CD86 and HLA DR in infected DC revealed significant (p M. tuberculosis in comparison to immature DC with no stimulation. Lipopolysaccharide (LPS from Salmonella abortus equi, a known DC maturation agent, was used as a positive control and showed a comparable up regulation of cell surface markers as observed with M. tuberculosis infected DC. It was revealed that the M. tuberculosis infected DC induced T cell proliferation. Conclusion These data clearly demonstrate that M. tuberculosis induces activation and maturation of human monocyte-derived immature DC as well as induces T cell proliferation in vitro.

  2. Skeletal site-specific effects of whole body vibration in mature rats: from deleterious to beneficial frequency-dependent effects.

    Science.gov (United States)

    Pasqualini, Marion; Lavet, Cédric; Elbadaoui, Mohamed; Vanden-Bossche, Arnaud; Laroche, Norbert; Gnyubkin, Vasily; Vico, Laurence

    2013-07-01

    Whole body vibration (WBV) is receiving increasing interest as an anti-osteoporotic prevention strategy. In this context, selective effects of different frequency and acceleration magnitude modalities on musculoskeletal responses need to be better defined. Our aim was to investigate the bone effects of different vibration frequencies at constant g level. Vertical WBV was delivered at 0.7 g (peak acceleration) and 8, 52 or 90 Hz sinusoidal vibration to mature male rats 10 min daily for 5 days/week for 4 weeks. Peak accelerations measured by skin or bone-mounted accelerometers at L2 vertebral and tibia crest levels revealed similar values between adjacent skin and bone sites. Local accelerations were greater at 8 Hz compared with 52 and 90 Hz and were greater in vertebra than tibia for all the frequencies tested. At 52 Hz, bone responses were mainly seen in L2 vertebral body and were characterized by trabecular reorganization and stimulated mineral apposition rate (MAR) without any bone volume alteration. At 90 Hz, axial and appendicular skeletons were affected as were the cortical and trabecular compartments. Cortical thickness increased in femur diaphysis (17%) along with decreased porosity; trabecular bone volume increased at distal femur metaphysis (23%) and even more at L2 vertebral body (32%), along with decreased SMI and increased trabecular connectivity. Trabecular thickness increased at the tibia proximal metaphysis. Bone cellular activities indicated a greater bone formation rate, which was more pronounced at vertebra (300%) than at long bone (33%). Active bone resorption surfaces were unaffected. At 8 Hz, however, hyperosteoidosis with reduced MAR along with increased resorption surfaces occurred in the tibia; hyperosteoidosis and trend towards decreased MAR was also seen in L2 vertebra. Trabecular bone mineral density was decreased at femur and tibia. Thus the most favorable regimen is 90 Hz, while deleterious effects were seen at 8 Hz. We concluded that

  3. Radiographic measurements of hip dysplasia at skeletal maturity - new reference intervals based on 2,038 19-year-old Norwegians

    Energy Technology Data Exchange (ETDEWEB)

    Laborie, Lene Bjerke; Rosendahl, Karen [University of Bergen, Department of Surgical Sciences, Bergen (Norway); Haukeland University Hospital, Department of Radiology, Bergen (Norway); Engesaeter, Ingvild Oevsteboe [University of Bergen, Department of Surgical Sciences, Bergen (Norway); Haukeland University Hospital, Department of Radiology, Bergen (Norway); Haukeland University Hospital, Department of Orthopaedic Surgery, Bergen (Norway); Lehmann, Trude Gundersen; Engesaeter, Lars Birger [University of Bergen, Department of Surgical Sciences, Bergen (Norway); Haukeland University Hospital, Department of Orthopaedic Surgery, Bergen (Norway); Sera, Francesco; Dezateux, Carol [UCL Institute of Child Health, MRC Centre of Epidemiology for Child Health, London (United Kingdom)

    2013-07-15

    Normative references for radiographic measurements commonly used in the diagnosis of developmental dysplasia of the hip at skeletal maturity are incomplete. The present study therefore aimed to establish new gender-specific standards for measurements reflecting the acetabular morphology, namely Sharp's angle, the acetabular roof angle of Toennis (AA) and the acetabular depth-width ratio (ADR), and measurements reflecting the position of the femoral head related to the acetabulum, namely the center-edge (CE) angle of Wiberg, the refined CE angle of Ogata, and the femoral head extrusion index (FHEI). The joint space width (JSW) is also reported. The population-based 1989 Bergen Birth Cohort (n = 3,935) was invited at age 19 years to a follow-up during 2007-09, of which 2,038 (52 %) attended. A standardized antero-posterior radiograph was assessed. The normative references are presented as mean {+-} standard deviation (SD) and 2.5-97.5 percentiles with 95 % confidence intervals. A total of 2,011 (841 males, 1,170 females, mean age 18.6 (SD 0.6)) radiographs were analyzed. Sharp's angle was 38.8 {+-} 3.5 in males and 40.7 {+-} 3.5 in females, with 97.5 percentiles of 46 and 47 , respectively. The CE angle was 32.1 {+-} 6.1 in males and 31.0 {+-} 6.1 in females, with 2.5 percentiles of 21 and 20 , respectively. The FHEI was 86.0 % {+-} 6.3 % in males and 85.6 % {+-} 6.6 % in females, with 2.5 percentiles of 74 and 73 , respectively. Updated gender-specific reference ranges for radiographic measurements commonly used for hip dysplasia at skeletal maturity are reported, similar to or slightly wider than those described in the literature. Statistically significant gender differences have been confirmed for most of the measurements. (orig.)

  4. Role of Active Contraction and Tropomodulins in Regulating Actin Filament Length and Sarcomere Structure in Developing Zebrafish Skeletal Muscle.

    Science.gov (United States)

    Mazelet, Lise; Parker, Matthew O; Li, Mei; Arner, Anders; Ashworth, Rachel

    2016-01-01

    Whilst it is recognized that contraction plays an important part in maintaining the structure and function of mature skeletal muscle, its role during development remains undefined. In this study the role of movement in skeletal muscle maturation was investigated in intact zebrafish embryos using a combination of genetic and pharmacological approaches. An immotile mutant line (cacnb1 (ts25) ) which lacks functional voltage-gated calcium channels (dihydropyridine receptors) in the muscle and pharmacological immobilization of embryos with a reversible anesthetic (Tricaine), allowed the study of paralysis (in mutants and anesthetized fish) and recovery of movement (reversal of anesthetic treatment). The effect of paralysis in early embryos (aged between 17 and 24 hours post-fertilization, hpf) on skeletal muscle structure at both myofibrillar and myofilament level was determined using both immunostaining with confocal microscopy and small angle X-ray diffraction. The consequences of paralysis and subsequent recovery on the localization of the actin capping proteins Tropomodulin 1 & 4 (Tmod) in fish aged from 17 hpf until 42 hpf was also assessed. The functional consequences of early paralysis were investigated by examining the mechanical properties of the larval muscle. The length-force relationship, active and passive tension, was measured in immotile, recovered and control skeletal muscle at 5 and 7 day post-fertilization (dpf). Recovery of muscle function was also assessed by examining swimming patterns in recovered and control fish. Inhibition of the initial embryonic movements (up to 24 hpf) resulted in an increase in myofibril length and a decrease in width followed by almost complete recovery in both moving and paralyzed fish by 42 hpf. In conclusion, myofibril organization is regulated by a dual mechanism involving movement-dependent and movement-independent processes. The initial contractile event itself drives the localization of Tmod1 to its sarcomeric

  5. Role of active contraction and tropomodulins in regulating actin filament length and sarcomere structure in developing zebrafish skeletal muscle

    Directory of Open Access Journals (Sweden)

    Lise eMazelet

    2016-03-01

    Full Text Available Whilst it is recognised that contraction plays an important part in maintaining the structure and function of mature skeletal muscle, its role during development remains undefined. In this study the role of movement in skeletal muscle maturation was investigated in intact zebrafish embryos using a combination of genetic and pharmacological approaches. An immotile mutant line (cacnb1ts25 which lacks functional voltage-gated calcium channels (dihydropyridine receptors in the muscle and pharmacological immobilisation of embryos with a reversible anaesthetic (Tricaine, allowed the study of paralysis (in mutants and anaesthetised fish and recovery of movement (reversal of anaesthetic treatment. The effect of paralysis in early embryos (aged between 17-24 hours post fertilisation, hpf on skeletal muscle structure at both myofibrillar and myofilament level was determined using both immunostaining with confocal microscopy and small angle X-ray diffraction. The consequences of paralysis and subsequent recovery on the localisation of the actin capping proteins Tropomodulin 1 &4 (Tmod in fish aged from 17hpf until 42hpf was also assessed. The functional consequences of early paralysis were investigated by examining the mechanical properties of the larval muscle. The length-force relationship, active and passive tension, was measured in immotile, recovered and control skeletal muscle at 5 and 7 day post fertilisation (dpf. Recovery of muscle function was also assessed by examining swimming patterns in recovered and control fish. Inhibition of the initial embryonic movements (up to 24 hpf resulted in an increase in myofibril length and a decrease in width followed by almost complete recovery in both moving and paralysed fish by 42hpf. In conclusion, myofibril organisation is regulated by a dual mechanism involving movement-dependent and movement-independent processes. The initial contractile event itself drives the localisation of Tmod1 to its sarcomeric

  6. Epiphyseal union of the cervical vertebral centra: its relationship to skeletal age and maturation of thoracic vertebral centra.

    Science.gov (United States)

    Albert, Midori A; Maier, Christopher A

    2013-11-01

    Epiphyseal union stages for cervical vertebral centra (ring epiphyses) were documented for 55 individuals (females and males, ages 14-27 years) from the Terry Collection, using the Albert and Maples method 1, to examine both its relationship to age at death and to thoracic data collected from the same individuals using the same method. Results showed a moderate correlation between cervical ring union and age (r = 0.63, p = 0.000), and a fairly low correlation between cervical and thoracic ring union (r = 0.41, p = 0.002). Paired samples t-tests yielded a statistically significant difference between cervical and thoracic union mean values (p = 0.01). Union progressed earlier in cervical vertebrae and in females. Results indicated fairly substantial variation in both sexes. Findings may serve as a basic guideline for estimating a general age range at death for unknown skeletal remains and to corroborate findings from other skeletal age indicators. © 2013 American Academy of Forensic Sciences.

  7. Gingival crevicular fluid alkaline phosphatase activity in relation to pubertal growth spurt and dental maturation: A multiple regression study

    Directory of Open Access Journals (Sweden)

    Perinetti, G.

    2016-04-01

    Full Text Available Introduction: The identification of the onset of the pubertal growth spurt has major clinical implications when dealing with orthodontic treatment in growing subjects. Aim: Through multivariate methods, this study evaluated possible relationships between the gingival crevicular fluid (GCF alkaline phosphatase (ALP activity and pubertal growth spurt and dentition phase. Materials and methods: One hundred healthy growing subjects (62 females, 38 males; mean age, 11.5±2.4 years were enrolled into this doubleblind, prospective, cross-sectional-design study. Phases of skeletal maturation (pre - pubertal, pubertal, post - pubertal was assessed using the cervical vertebral maturation method. Samples of GCF for the ALP activity determination were collected at the mesial and distal sites of the mandibular central incisors. The phases of the dentition were recorded as intermediate mixed, late mixed, or permanent. A multinomial multiple logistic regression model was used to assess relationships of the enzymatic activity to growth phases and dentition phases. Results: The GCF ALP activity was greater in the pubertal growth phase as compared to the pre - pubertal and post - pubertal growth phases. Significant adjusted odds ratios for the GCF ALP activity for the pre - pubertal and post - pubertal subjects, in relation to the pubertal group, were 0.76 and 0.84, respectively. No significant correlations were seen for the dentition phase. Conclusions: The GCF ALP activity is a valid candidate as a non - invasive biomarker for the identification of the pubertal growth spurt irrespective of the dentition phase.

  8. A comparison of cervical vertebral maturation assessment of skeletal growth stages with chronological age in Thai between cleft lip and palate and non-cleft patients.

    Science.gov (United States)

    Pisek, Poonsak; Godfrey, Keith; Manosudprasit, Montian; Wangsrimongkol, Tasanee; Leelasinjaroen, Pornnapha

    2013-09-01

    (1) To search for any difference in chronological age related to stages of the cervical vertebral maturation index stages (CVMIs) comparing groups of cleft lip and palate (CLP) and non-cleft (non-CLP) subjects; (2) To investigate the relationship between chronological age and CVMIs in both groups of subjects. Cervical vertebrae C2, C3, C4 were assessed on 1,549 cephalometric films (503 CLP films, 1,046 non-CLP films of subjects aged 5 to 18 years) using Hassel and Farman's method. T-tests showed mean chronological ages of CVMIs 2, 3 and 6 were different at p = 0.001, 0.024 and 0.016, respectively. CVMIs 1, 4 and 5 showed no significant differences. The CLP group achieved each CVMI score one year ahead of the non-CLP group, except for CVMI 4. Spearman's rank order correlations were r = 0.80 (95% CI: 0.76-0.83) for CLP, and 0.77 (95% CI: 0.74-0.79) for non-CLP. CLP subjects tended to have a slightly advanced growth compared with non-CLP subjects. A high correlation coefficient was found between chronological age and cervical vertebral skeletal maturation.

  9. Noradrenaline spillover during exercise in active versus resting skeletal muscle in man

    DEFF Research Database (Denmark)

    Savard, G; Strange, S; Kiens, Bente

    1987-01-01

    Increases in plasma noradrenaline (NA) concentration occur during moderate to heavy exercise in man. This study was undertaken to examine the spillover of NA from both resting and contracting skeletal muscle during exercise. Six male subjects performed one-legged knee-extension so that all...... in the exercising leg than in the resting leg both during 50% and 100% leg exercise. These results suggest that contracting skeletal muscle may contribute to a larger extent than resting skeletal muscle to increasing the level of plasma NA during exercise. Contractile activity may influence the NA spillover from...

  10. Melanocortin 4 Receptor Activation Attenuates Mitochondrial Dysfunction in Skeletal Muscle of Diabetic Rats.

    Science.gov (United States)

    Zhang, Hao-Hao; Liu, Jiao; Qin, Gui-Jun; Li, Xia-Lian; Du, Pei-Jie; Hao, Xiao; Zhao, Di; Tian, Tian; Wu, Jing; Yun, Meng; Bai, Yan-Hui

    2017-11-01

    A previous study has confirmed that the central melanocortin system was able to mediate skeletal muscle AMP-activated protein kinase (AMPK) activation in mice fed a high-fat diet, while activation of the AMPK signaling pathway significantly induced mitochondrial biogenesis. Our hypothesis was that melanocortin 4 receptor (MC4R) was involved in the development of skeletal muscle injury in diabetic rats. In this study, we treated diabetic rats intracerebroventricularly with MC4R agonist R027-3225 or antagonist SHU9119, respectively. Then, we measured the production of reactive oxygen species (ROS), the levels of malondialdehyde (MDA) and glutathione (GSH), the mitochondrial DNA (mtDNA) content and mitochondrial biogenesis, and the protein levels of p-AMPK, AMPK, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α), sirtuin 1 (SIRT1), and manganese superoxide dismutase (MnSOD) in the skeletal muscle of diabetic rats. The results showed that there was significant skeletal muscle injury in the diabetic rats along with serious oxidative stress and decreased mitochondrial biogenesis. Treatment with R027-3225 reduced oxidative stress and induced mitochondrial biogenesis in skeletal muscle, and also activated the AMPK-SIRT1-PGC-1α signaling pathway. However, diabetic rats injected with MC4R antagonist SHU9119 showed an aggravated oxidative stress and mitochondrial dysfunction in skeletal muscle. In conclusion, our results revealed that MC4R activation was able to attenuate oxidative stress and mitochondrial dysfunction in skeletal muscle induced by diabetes partially through activating the AMPK-SIRT1-PGC-1α signaling pathway. J. Cell. Biochem. 118: 4072-4079, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Activated protein C attenuates acute ischaemia reperfusion injury in skeletal muscle.

    LENUS (Irish Health Repository)

    Dillon, J P

    2012-02-03

    Activated protein C (APC) is an endogenous anti-coagulant with anti-inflammatory properties. The purpose of the present study was to evaluate the effects of activated protein C in the setting of skeletal muscle ischaemia reperfusion injury (IRI). IRI was induced in rats by applying rubber bands above the levels of the greater trochanters bilaterally for a period of 2h followed by 12h reperfusion. Treatment groups received either equal volumes of normal saline or activated protein C prior to tourniquet release. Following 12h reperfusion, muscle function was assessed electrophysiologically by electrical field stimulation. The animals were then sacrificed and skeletal muscle harvested for evaluation. Activated protein C significantly attenuated skeletal muscle reperfusion injury as shown by reduced myeloperoxidase content, wet to dry ratio and electrical properties of skeletal muscle. Further in vitro work was carried out on neutrophils isolated from healthy volunteers to determine the direct effect of APC on neutrophil function. The effects of APC on TNF-alpha stimulated neutrophils were examined by measuring CD18 expression as well as reactive oxygen species generation. The in vitro work demonstrated a reduction in CD18 expression and reactive oxygen species generation. We conclude that activated protein C may have a protective role in the setting of skeletal muscle ischaemia reperfusion injury and that this is in part mediated by a direct inhibitory effect on neutrophil activation.

  12. Oxidative stress (glutathionylation and Na,K-ATPase activity in rat skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Carsten Juel

    Full Text Available Changes in ion distribution across skeletal muscle membranes during muscle activity affect excitability and may impair force development. These changes are counteracted by the Na,K-ATPase. Regulation of the Na,K-ATPase is therefore important for skeletal muscle function. The present study investigated the presence of oxidative stress (glutathionylation on the Na,K-ATPase in rat skeletal muscle membranes.Immunoprecipitation with an anti-glutathione antibody and subsequent immunodetection of Na,K-ATPase protein subunits demonstrated 9.0±1.3% and 4.1±1.0% glutathionylation of the α isoforms in oxidative and glycolytic skeletal muscle, respectively. In oxidative muscle, 20.0±6.1% of the β1 units were glutathionylated, whereas 14.8±2.8% of the β2-subunits appear to be glutathionylated in glycolytic muscle. Treatment with the reducing agent dithiothreitol (DTT, 1 mM increased the in vitro maximal Na,K-ATPase activity by 19% (P<0.05 in membranes from glycolytic muscle. Oxidized glutathione (GSSG, 0-10 mM increased the in vitro glutathionylation level detected with antibodies, and decreased the in vitro maximal Na,K-ATPase activity in a dose-dependent manner, and with a larger effect in oxidative compared to glycolytic skeletal muscle.This study demonstrates the existence of basal glutathionylation of both the α and the β units of rat skeletal muscle Na,K-ATPase. In addition, the study suggests a negative correlation between glutathionylation levels and maximal Na,K-ATPase activity.Glutathionylation likely contributes to the complex regulation of Na,K-ATPase function in skeletal muscle. Especially, glutathionylation induced by oxidative stress may have a role in Na,K-ATPase regulation during prolonged muscle activity.

  13. The relationship between skeletal muscle mitochondrial citrate synthase activity and whole body oxygen uptake adaptations in response to exercise training

    DEFF Research Database (Denmark)

    Vigelsø Hansen, Andreas; Andersen, Nynne Bjerre; Dela, Flemming

    2014-01-01

    Citrate synthase (CS) activity is a validated biomarker for mitochondrial density in skeletal muscle. CS activity is also used as a biochemical marker of the skeletal muscle oxidative adaptation to a training intervention, and a relationship between changes in whole body aerobic capacity and chan......Citrate synthase (CS) activity is a validated biomarker for mitochondrial density in skeletal muscle. CS activity is also used as a biochemical marker of the skeletal muscle oxidative adaptation to a training intervention, and a relationship between changes in whole body aerobic capacity...

  14. Assessment of mandibular growth by skeletal scintigraphy

    International Nuclear Information System (INIS)

    Kaban, L.B.; Cisneros, G.J.; Heyman, S.; Treves, S.

    1982-01-01

    Accurate assessment of facial skeletal growth remains a major problem in craniomaxillofacial surgery. Current methods include: (1) comparisons of chronologic age with growth histories of the patient and the family, (2) hand-wrist radiographs compared with a standard, and (3) serial cephalometric radiographs. Uptake of technetium-99m methylene diphosphonate into bone is a reflection of current metabolic activity and blood flow. Therefore, scintigraphy with this radiopharmaceutical might serve as a good method of assessing skeletal growth. Thirty-four patients, ranging in age from 15 months to 22 years, who were undergoing skeletal scintigrams for acute pathologic conditions of the extremities, were used to develop standards of uptake based on age and skeletal maturation. The results indicate that skeletal scintigraphy may be useful in evaluation of mandibular growth

  15. Exercise induces transient transcriptional activation of the PGC-1a gene in human skeletal muscle

    DEFF Research Database (Denmark)

    Pilegaard, Henriette; Saltin, Bengt; Neufer, P. Darrell

    2003-01-01

    Endurance exercise training induces mitochondrial biogenesis in skeletal muscle. The peroxisome proliferator activated receptor co-activator 1a (PGC-1a) has recently been identified as a nuclear factor critical for coordinating the activation of genes required for mitochondrial biogenesis in cell...... culture and rodent skeletal muscle. To determine whether PGC-1a transcription is regulated by acute exercise and exercise training in human skeletal muscle, seven male subjects performed 4 weeks of one-legged knee extensor exercise training. At the end of training, subjects completed 3 h of two......-legged knee extensor exercise. Biopsies were obtained from the vastus lateralis muscle of both the untrained and trained legs before exercise and after 0, 2, 6 and 24 h of recovery. Time to exhaustion (2 min maximum resistance), as well as hexokinase II (HKII), citrate synthase and 3-hydroxyacyl...

  16. Differentially activated macrophages orchestrate myogenic precursor cell fate during human skeletal muscle regeneration

    DEFF Research Database (Denmark)

    Saclier, Marielle; Yacoub-Youssef, Houda; Mackey, Abigail

    2013-01-01

    , we explored both in vitro and in vivo, in human, the interactions of differentially activated MPs with myogenic precursor cells (MPCs) during adult myogenesis and skeletal muscle regeneration. We showed in vitro that through the differential secretion of cytokines and growth factors, proinflammatory...... anti-inflammatory markers. These data demonstrate for the first time in human that MPs sequentially orchestrate adult myogenesis during regeneration of damaged skeletal muscle. These results support the emerging concept that inflammation, through MP activation, controls stem cell fate and coordinates......Macrophages (MPs) exert either beneficial or deleterious effects on tissue repair, depending on their activation/polarization state. They are crucial for adult skeletal muscle repair, notably by acting on myogenic precursor cells. However, these interactions have not been fully characterized. Here...

  17. Effects of alpha-AMPK knockout on exercise-induced gene activation in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Jørgensen, Sebastian Beck; Wojtaszewski, Jørgen; Viollet, Benoit

    2005-01-01

    We tested the hypothesis that 5'AMP-activated protein kinase (AMPK) plays an important role in regulating the acute, exercise-induced activation of metabolic genes in skeletal muscle, which were dissected from whole-body a2- and a1-AMPK knockout (KO) and wild-type (WT) mice at rest, after treadmi...

  18. Effect of fullerene C(60 on ATPase activity and superprecipitation of skeletal muscle actomyosin

    Directory of Open Access Journals (Sweden)

    K. S. Andreichenko

    2013-04-01

    Full Text Available Creation of new biocompatible nanomaterials, which can exhibit the specific biological effects, is an important complex problem that requires the use of last accomplishments of biotechnology. The effect of pristine water-soluble fullerene C60 on ATPase activity and superprecipitation reaction of rabbit skeletal muscle natural actomyosin has been revealed, namely an increase of actomyosin superprecipitation and Мg2+, Са2+– and K+-ATPase activity by fullerene was investigated. We conclude that this finding offers a real possibility for the regulation of contraction-relaxation of skeletal muscle with fullerene C60.

  19. The pro-Forms of Insulin-Like Growth Factor I (IGF-I) Are Predominant in Skeletal Muscle and Alter IGF-I Receptor Activation

    Science.gov (United States)

    Durzyńska, Julia; Philippou, Anastassios; Brisson, Becky K.; Nguyen-McCarty, Michelle

    2013-01-01

    IGF-I is a key regulator of muscle development and growth. The pre-pro-peptide produced by the Igf1gene undergoes several posttranslational processing steps to result in a secreted mature protein, which is thought to be the obligate ligand for the IGF-I receptor (IGF-IR). The goals of this study were to determine what forms of IGF-I exist in skeletal muscle, and whether the mature IGF-I protein was the only form able to activate the IGF-IR. We measured the proportion of IGF-I species in murine skeletal muscle and found that the predominant forms were nonglycosylated pro-IGF-I and glycosylated pro-IGF-I, which retained the C-terminal E peptide extension, instead of mature IGF-I. These forms were validated using samples subjected to viral expression of IGF-I combined with furin and glycosidase digestion. To determine whether the larger molecular weight IGF-I forms were also ligands for the IGF-IR, we generated each specific form through transient transfection of 3T3 cells and used the enriched media to perform kinase receptor activation assays. Compared with mature IGF-I, nonglycosylated pro-IGF-I had similar ability to activate the IGF-IR, whereas glycosylation of pro-IGF-I significantly reduced receptor activation. Thus, it is important to understand not only the quantity, but also the proportion of IGF-I forms produced, to evaluate the true biological activity of this growth factor. PMID:23407451

  20. Studies on thyroid activity at sexual maturity in the male and female Bengal goats

    International Nuclear Information System (INIS)

    Varshney, V.P.; Pande, J.K.; Sanwal, P.C.

    1980-01-01

    Thyroid activity at sexual maturity in the male and female Black Bengal goats was investigated. No change could be recorded at the attainment of sexual maturity in either of the sexes. The cyclic female goats also failed to reflect any change in the thyroid activity during any phase of the oestrous cycle. Again the male goats also failed to reflect any differences in the thyroid activity from the females, either during their immature, or during their mature life. The observations presented thus reflect that the thyroid activity in goats is not influenced by the attainments of sexual maturity or by the sex, in this species. The thyroid gland activity was assessed by using the in vitro technique of triiodothyronine- 125 I uptake by resin. (author)

  1. Maturational differences in physical self- perceptions and the relationship with physical activity in early adolescent girls.

    Science.gov (United States)

    Niven, Alisa G; Fawkner, Samantha G; Knowles, Anne-Marie; Stephenson, Claire

    2007-11-01

    This cross-sectional study examined the relationship between physical self-perceptions (PSPs), maturation, and physical activity and compared the strength of the relationships of biological and chronological age with PSPs in early adolescent girls (N = 208; mean age = 11.83 +/- 0.39 years). Participants completed the Physical Activity Questionnaire for Older Children, the Children's Physical Self-Perception Profile, and the Pubertal Development Scale. Results indicated that PSPs were significantly and moderately correlated with physical activity. There were no differences in physical activity between maturation stages. Girls who were in the early stages of maturation had significantly more positive perceptions of body attractiveness and physical self-worth than girls in the mid stages of maturation. There was no evidence of a relationship between PSPs and chronological age. This study provided further support for the relationship between PSPs and physical activity and the relationship between maturation and aspects of PSPs. In this age group, maturation does not appear to be related to physical activity or the PSPs most strongly influential on physical activity behavior.

  2. Constitutive activation of IKK2/NF-κB impairs osteogenesis and skeletal development.

    Directory of Open Access Journals (Sweden)

    Gaurav Swarnkar

    Indian hedgehog and alkaline phosphatase, and the early markers Aggrecan and type-II collagen were reduced in Cre+IKK2ca_w/f and Cre+IKK2ca_f/f mice. Altogether, the in-vitro, in vivo and ex-vivo evidence suggest that IKK2ca perturbs osteoblast and chondrocyte maturation and impairs skeletal development.

  3. Fueling the engine: induction of AMP-activated protein kinase in trout skeletal muscle by swimming

    NARCIS (Netherlands)

    Magnoni, L.J.; Palstra, A.P.; Planas, J.V.

    2014-01-01

    AMP-activated protein kinase (AMPK) is well known to be induced by exercise and to mediate important metabolic changes in the skeletal muscle of mammals. Despite the physiological importance of exercise as a modulator of energy use by locomotory muscle, the regulation of this enzyme by swimming has

  4. Selumetinib Attenuates Skeletal Muscle Wasting in Murine Cachexia Model through ERK Inhibition and AKT Activation.

    Science.gov (United States)

    Quan-Jun, Yang; Yan, Huo; Yong-Long, Han; Li-Li, Wan; Jie, Li; Jin-Lu, Huang; Jin, Lu; Peng-Guo, Chen; Run, Gan; Cheng, Guo

    2017-02-01

    Cancer cachexia is a multifactorial syndrome affecting the skeletal muscle. Previous clinical trials showed that treatment with MEK inhibitor selumetinib resulted in skeletal muscle anabolism. However, it is conflicting that MAPK/ERK pathway controls the mass of the skeletal muscle. The current study investigated the therapeutic effect and mechanisms of selumetinib in amelioration of cancer cachexia. The classical cancer cachexia model was established via transplantation of CT26 colon adenocarcinoma cells into BALB/c mice. The effect of selumetinib on body weight, tumor growth, skeletal muscle, food intake, serum proinflammatory cytokines, E3 ligases, and MEK/ERK-related pathways was analyzed. Two independent experiments showed that 30 mg/kg/d selumetinib prevented the loss of body weight in murine cachexia mice. Muscle wasting was attenuated and the expression of E3 ligases, MuRF1 and Fbx32, was inhibited following selumetinib treatment of the gastrocnemius muscle. Furthermore, selumetinib efficiently reduced tumor burden without influencing the cancer cell proliferation, cumulative food intake, and serum cytokines. These results indicated that the role of selumetinib in attenuating muscle wasting was independent of cancer burden. Detailed analysis of the mechanism revealed AKT and mTOR were activated, while ERK, FoxO3a, and GSK3β were inhibited in the selumetinib -treated cachexia group. These indicated that selumetinib effectively prevented skeletal muscle wasting in cancer cachexia model through ERK inhibition and AKT activation in gastrocnemius muscle via cross-inhibition. The study not only elucidated the mechanism of MEK/ERK inhibition in skeletal muscle anabolism, but also validated selumetinib therapy as an effective intervention against cancer cachexia. Mol Cancer Ther; 16(2); 334-43. ©2016 AACR. ©2016 American Association for Cancer Research.

  5. Gas6 downregulation impaired cytoplasmic maturation and pronuclear formation independent to the MPF activity.

    Directory of Open Access Journals (Sweden)

    Kyeoung-Hwa Kim

    Full Text Available Previously, we found that the growth arrest-specific gene 6 (Gas6 is more highly expressed in germinal vesicle (GV oocytes than in metaphase II (MII oocytes using annealing control primer (ACP-PCR technology. The current study was undertaken to investigate the role of Gas6 in oocyte maturation and fertilization using RNA interference (RNAi. Interestingly, despite the specific and marked decrease in Gas6 mRNA and protein expression in GVs after Gas6 RNAi, nuclear maturation including spindle structures and chromosome segregation was not affected. The only discernible effect induced by Gas6 RNAi was a change in maturation promoting factor (MPF activity. After parthenogenetic activation, Gas6 RNAi-treated oocytes at the MII stage had not developed further and arrested at MII (90.0%. After stimulation with Sr(2+, Gas6-silenced MII oocytes had markedly reduced Ca(2+ oscillation and exhibited no exocytosis of cortical granules. In these oocytes, sperm penetration occurred during fertilization but not pronucleus (PN formation. By roscovitine and colcemid treatment, we found that the Gas6 knockdown affected cytoplasmic maturation directly, independent to the changed MPF activity. These results strongly suggest that 1 the Gas6 signaling itself is important to the cytoplasmic maturation, but not nuclear maturation, and 2 the decreased Gas6 expression and decreased MPF activity separately or mutually influence sperm head decondensation and PN formation.

  6. Activation-Dependent Rapid Postsynaptic Clustering of Glycine Receptors in Mature Spinal Cord Neurons

    Science.gov (United States)

    Eto, Kei; Murakoshi, Hideji; Watanabe, Miho; Hirata, Hiromi; Moorhouse, Andrew J.; Ishibashi, Hitoshi

    2017-01-01

    Abstract Inhibitory synapses are established during development but continue to be generated and modulated in strength in the mature nervous system. In the spinal cord and brainstem, presynaptically released inhibitory neurotransmitter dominantly switches from GABA to glycine during normal development in vivo. While presynaptic mechanisms of the shift of inhibitory neurotransmission are well investigated, the contribution of postsynaptic neurotransmitter receptors to this shift is not fully elucidated. Synaptic clustering of glycine receptors (GlyRs) is regulated by activation-dependent depolarization in early development. However, GlyR activation induces hyperpolarization after the first postnatal week, and little is known whether and how presynaptically released glycine regulates postsynaptic receptors in a depolarization-independent manner in mature developmental stage. Here we developed spinal cord neuronal culture of rodents using chronic strychnine application to investigate whether initial activation of GlyRs in mature stage could change postsynaptic localization of GlyRs. Immunocytochemical analyses demonstrate that chronic blockade of GlyR activation until mature developmental stage resulted in smaller clusters of postsynaptic GlyRs that could be enlarged upon receptor activation for 1 h in the mature stage. Furthermore, live cell-imaging techniques show that GlyR activation decreases its lateral diffusion at synapses, and this phenomenon is dependent on PKC, but neither Ca2+ nor CaMKII activity. These results suggest that the GlyR activation can regulate receptor diffusion and cluster size at inhibitory synapses in mature stage, providing not only new insights into the postsynaptic mechanism of shifting inhibitory neurotransmission but also the inhibitory synaptic plasticity in mature nervous system. PMID:28197549

  7. Effects of the belt electrode skeletal muscle electrical stimulation system on lower extremity skeletal muscle activity: Evaluation using positron emission tomography.

    Science.gov (United States)

    Numata, Hitoaki; Nakase, Junsuke; Inaki, Anri; Mochizuki, Takafumi; Oshima, Takeshi; Takata, Yasushi; Kinuya, Seigo; Tsuchiya, Hiroyuki

    2016-01-01

    Lower-extremity muscle weakness in athletes after lower limb trauma or surgery can hinder their return to sports, and the associated muscle atrophy may lead to deterioration in performance after returning to sports. Recently, belt electrode skeletal muscle electrical stimulation (B-SES) which can contract all the lower limb skeletal muscles simultaneously was developed. However, no study has evaluated skeletal muscle activity with B-SES. Since only superficial muscles as well as a limited number of muscles can be investigated using electromyography, we investigated whether positron emission tomography (PET) can evaluate the activity of all the skeletal muscles in the body simultaneously. The purpose of this study was to evaluate the effectiveness of the B-SES system using PET. Twelve healthy males (mean age, 24.3 years) were divided into two groups. The subjects in the control group remained in a sitting position for 10 min, and [(18)F] fluorodeoxyglucose (FDG) was intravenously injected. In the exercise group, subjects exercised using the B-SES system for 20 min daily for three consecutive days as a pre-test exercise. On the measurement day, they exercised for 10 min, received an injection of FDG, and exercised for another 10 min. PET-computed tomography images were obtained in each group 60 min after the FDG injection. Regions of interest were drawn in each lower-extremity muscle. We compared each skeletal muscle metabolism using the standardized uptake value. In the exercise group, FDG accumulation in the gluteus maximus, gluteus medius, gluteus minimus, quadriceps femoris, sartorius, and hamstrings was significantly higher than the muscles in the control (P skeletal muscle activity of the gluteal muscles as well as the most lower-extremity muscles simultaneously. Copyright © 2015 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

  8. Imbalance in SOD/CAT activities in rat skeletal muscles submitted to treadmill training exercise.

    Science.gov (United States)

    Pinho, Ricardo A; Andrades, Michael E; Oliveira, Marcos R; Pirola, Aline C; Zago, Morgana S; Silveira, Paulo C L; Dal-Pizzol, Felipe; Moreira, José Cláudio F

    2006-10-01

    The association between physical exercise and oxidative damage in the skeletal musculature has been the focus of many studies in literature, but the balance between superoxide dismutase and catalase activities and its relation to oxidative damage is not well established. Thus, the aim of the present study was to investigate the association between regular treadmill physical exercise, oxidative damage and antioxidant defenses in skeletal muscle of rats. Fifteen male Wistar rats (8-12 months) were randomly separated into two groups (trained n=9 and untrained n=6). Trained rats were treadmill-trained for 12 weeks in progressive exercise (velocity, time, and inclination). Training program consisted in a progressive exercise (10 m/min without inclination for 10 min/day). After 1 week the speed, time and inclination were gradually increased until 17 m/min at 10% for 50 min/day. After the training period animals were killed, and gastrocnemius and quadriceps were surgically removed to the determination of biochemical parameters. Lipid peroxidation, protein oxidative damage, catalase, superoxide dismutase and citrate synthase activities, and muscular glycogen content were measured in the isolated muscles. We demonstrated that there is a different modulation of CAT and SOD in skeletal muscle in trained rats when compared to untrained rats (increased SOD/CAT ratio). TBARS levels were significantly decreased and, in contrast, a significant increase in protein carbonylation was observed. These results suggest a non-described adaptation of skeletal muscle against exercise-induced oxidative stress.

  9. Myofibril ATPase activity of cardiac and skeletal muscle of exhaustively exercised rats.

    Science.gov (United States)

    Belcastro, A N; Turcotte, R; Rossiter, M; Secord, D; Maybank, P E

    1984-01-01

    The activation characteristics of Mg-ATP and Ca2+ on cardiac and skeletal muscle myofibril ATPase activity were studied in rats following a run to exhaustion. In addition, the effect of varying ionic strength was determined on skeletal muscle from exhausted animals. The exhausted group (E) ran at a speed of 25 m min-1 with an 8% incline. Myofibril ATPase activities for control (C) and E were determined with 1, 3 and 5 mM Mg-ATP and 1 and 10 microM Ca2+ at pH 7.0 and 30 degrees C. For control skeletal muscle, at 1 and 10 microM Ca2+, there was an increase in ATPase activity from 1 to 5 mM Mg-ATP (P less than 0.05). For E animals the myofibril ATPase activities at 10 microM Ca2+ and all Mg-ATP concentrations were similar to C (P greater than 0.05). At 1.0 microM Ca2+ and all Mg-ATP concentrations were similar to C (P greater than 0.05). At 1.0 microM Ca2+ the activities at 3 and 5 mM Mg-ATP were greater for the E animals (P less than 0.05). Increasing KCl concentrations resulted in greater inhibition for E animals. With cardiac muscle, the myofibril ATPase activities at 1.0 microM free Ca2+ were lower for E at all Mg-ATP levels (P less than 0.05). In contrast, at 10 microM Ca2+, the E group exhibited an elevated myofibril ATPase activity. The results indicate that Mg-ATP and Ca2+ activation of cardiac and skeletal muscle myofibril ATPase is altered with exhaustive exercise.

  10. Nitric oxide and Na,K-ATPase activity in rat skeletal muscle

    DEFF Research Database (Denmark)

    Juel, Carsten

    2016-01-01

    Aim: It has been suggested that nitric oxide (NO) stimulates the Na,K-ATPase in cardiac myocytes. Therefore, the aims of this study were to investigate whether NO increases Na,K-ATPase activity in skeletal muscle and, if that is the case, to identify the underlying mechanism. Method: The study used...... isolated rat muscle, muscle homogenates and purified membranes as model systems. Na,K-ATPase activity was quantified from phosphate release due to ATP hydrolysis. Results: Exposure to the NO donor spermine NONOate (10 μm) increased the maximal Na,K-ATPase activity by 27% in isolated glycolytic muscles...... activity was depressed by oxidized glutathione. Conclusion: NO and cGMP stimulate the Na,K-ATPase in glycolytic skeletal muscle. Direct S-nitrosylation and interference with S-glutathionylation seem to be excluded. In addition, phosphorylation of phospholemman at serine 68 is not involved. Most likely...

  11. Antioxidant and antiproliferative activities in different maturation stages of broccoli (Brassica oleracea Italica) biofortified with selenium.

    Science.gov (United States)

    Bachiega, Patricia; Salgado, Jocelem Mastrodi; de Carvalho, João Ernesto; Ruiz, Ana Lúcia T G; Schwarz, Kélin; Tezotto, Tiago; Morzelle, Maressa Caldeira

    2016-01-01

    In this work, three different broccoli maturity stages subjected to biofortification with selenium were evaluated for antioxidant and antiproliferative activities. Antioxidant trials have shown that the maturation stages biofortified with selenium had significantly higher amounts of phenolic compounds and antioxidant activity, especially seedlings. Although non-polar extracts of all samples show antiproliferative activity, the extract of broccoli seedlings biofortified with selenium stood out, presenting cytocidal activity for a glioma line (U251, GI50 28.5 mg L(-1)). Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Predominant alpha2/beta2/gamma3 AMPK activation during exercise in human skeletal muscle

    DEFF Research Database (Denmark)

    Birk, Jesper Bratz; Wojtaszewski, Jørgen

    2006-01-01

    -Thr-172 AMPK phosphorylation (r2 = 0.84, P important actor in exercise-regulated AMPK signalling in human skeletal muscle, probably mediating phosphorylation of ACCß.......5'AMP-activated protein kinase (AMPK) is a key regulator of cellular metabolism and is regulated in muscle during exercise. We have previously established that only three of 12 possible AMPK a/ß/¿-heterotrimers are present in human skeletal muscle. Previous studies describe discrepancies between...... total AMPK activity and regulation of its target acetyl-CoA-carboxylase (ACC)ß. Also, exercise training decreases expression of the regulatory ¿3 AMPK subunit and attenuates a2 AMPK activity during exercise. We hypothesize that these observations reflect a differential regulation of the AMPK...

  13. The relationship between skeletal muscle mitochondrial citrate synthase activity and whole body oxygen uptake adaptations in response to exercise training

    DEFF Research Database (Denmark)

    Vigelsø, Andreas; Andersen, Nynne B; Dela, Flemming

    2014-01-01

    Citrate synthase (CS) activity is a validated biomarker for mitochondrial density in skeletal muscle. CS activity is also used as a biochemical marker of the skeletal muscle oxidative adaptation to a training intervention, and a relationship between changes in whole body aerobic capacity and chan......Citrate synthase (CS) activity is a validated biomarker for mitochondrial density in skeletal muscle. CS activity is also used as a biochemical marker of the skeletal muscle oxidative adaptation to a training intervention, and a relationship between changes in whole body aerobic capacity...... and changes in CS activity is often assumed. However, this relationship and absolute values of CS and maximal oxygen uptake (V.O2max) has never been assessed across different studies. A systematic PubMed search on literature published from 1983 to 2013 was performed. The search profile included: citrate...... and CS activity. 70 publications with 97 intervention groups were included. There was a positive (r = 0.45) correlation (P

  14. Traditional growing rod versus magnetically controlled growing rod for treatment of early onset scoliosis: Cost analysis from implantation till skeletal maturity.

    Science.gov (United States)

    Wong, Carlos King Ho; Cheung, Jason Pui Yin; Cheung, Prudence Wing Hang; Lam, Cindy Lo Kuen; Cheung, Kenneth Man Chee

    2017-01-01

    incurred by the TGR groups from year 4 to skeletal maturity. The use of dual MCGRs, regardless of its 2- or 3-year exchange, was only cost saving and less expensive than the dual TGRs for EOS treatment from the fourth year of continuous treatment. Despite higher patient-related costs during MCGR treatment, it is important to consider the reduced risks and mental burden suffered by these children during repeat surgeries. With improved knowledge of the costs associated with long-term MCGR use, better constructed cost-effectiveness studies can be performed in the future.

  15. Effect of maturity and harvest season on antioxidant activity ...

    African Journals Online (AJOL)

    Libaf 2

    2013-07-17

    Jul 17, 2013 ... The ability of M. citrifolia fruits to inhibit NO production by LPS- activated RAW 264.7 ..... rutin content than those reported in noni of Costa Rica; for scopoletin, we .... vegetales promisorios. Rev. Soc. Quím. Perú. 73(3):142-149.

  16. Effects of cutting and maturity on antioxidant activity of fresh-cut tomatoes

    NARCIS (Netherlands)

    Moreira Lana, M.; Tijskens, L.M.M.; Kooten, van O.

    2005-01-01

    To investigate the changes in total antioxidant activity of fresh-cut tomato during storage, tomato fruits harvested at three different stages of maturity were cut into 7-mm thick slices and stored at 5°C. Intact (control) fruits were stored in the same conditions. The antioxidant activity was

  17. Effects of cutting and maturity on antioxidant activity of fresh-cut tomatoes

    NARCIS (Netherlands)

    Moreira Lana, M.; Tijskens, L.M.M.

    2006-01-01

    To investigate the changes in total antioxidant activity of fresh-cut tomato during storage, tomato fruits harvested at three different stages of maturity were cut into 7-mm thick slices and stored at 5 °C. Intact fruits were stored in the same conditions as a control. The antioxidant activity was

  18. Characterization of proteolytic and anti-proteolytic activity involvement in sterlet spermatozoon maturation

    Czech Academy of Sciences Publication Activity Database

    Dzyuba, V.; Słowińska, M.; Cosson, J.; Ciereszko, A.; Boryshpolets, S.; Štěrba, Ján; Rodina, M.; Linhart, O.; Dzyuba, B.

    2016-01-01

    Roč. 42, č. 6 (2016), s. 1755-1766 ISSN 0920-1742 R&D Projects: GA MŠk(CZ) EE2.3.30.0032 Institutional support: RVO:60077344 Keywords : amidase activity * anti-proteolytic activity * casein and gelatin zymography * siberian sturgeon sperm * spermatozoon maturation * sterlet sperm Subject RIV: ED - Physiology Impact factor: 1.647, year: 2016

  19. Cytoskeleton, L-type Ca2+ and stretch activated channels in injured skeletal muscle

    Directory of Open Access Journals (Sweden)

    Fabio Francini

    2013-07-01

    Full Text Available The extra-sarcomeric cytoskeleton (actin microfilaments and anchoring proteins is involved in maintaining the sarco-membrane stiffness and integrity and in turn the mechanical stability and function of the intra- and sub-sarcoplasmic proteins. Accordingly, it regulates Ca2+ entry through the L-type Ca2+ channels and the mechano-sensitivity of the stretch activated channels (SACs. Moreover, being intra-sarcomeric cytoskeleton bound to costameric proteins and other proteins of the sarcoplasma by intermediate filaments, as desmin, it integrates the properties of the sarcolemma with the skeletal muscle fibres contraction. The aim of this research was to compare the cytoskeleton, SACs and the ECC alterations in two different types of injured skeletal muscle fibres: by muscle denervation and mechanical overload (eccentric contraction. Experiments on denervation were made in isolated Soleus muscle of male Wistar rats; forced eccentric-contraction (EC injury was achieved in Extensor Digitorum Longus muscles of Swiss mice. The method employed conventional intracellular recording with microelectrodes inserted in a single fibre of an isolated skeletal muscle bundle. The state of cytoskeleton was evaluated by recording SAC currents and by evaluating the resting membrane potential (RMP value determined in current-clamp mode. The results demonstrated that in both injured skeletal muscle conditions the functionality of L-type Ca2+ current, ICa, was affected. In parallel, muscle fibres showed an increase of the resting membrane permeability and of the SAC current. These issues, together with a more depolarized RMP are an index of altered cytoskeleton. In conclusion, we found a symilar alteration of ICa, SAC and cytoskeleton in both injured skeletal muscle conditions.

  20. Biocultural approach of the association between maturity and physical activity in youth.

    Science.gov (United States)

    Werneck, André O; Silva, Danilo R; Collings, Paul J; Fernandes, Rômulo A; Ronque, Enio R V; Coelho-E-Silva, Manuel J; Sardinha, Luís B; Cyrino, Edilson S

    2017-11-13

    To test the biocultural model through direct and indirect associations between biological maturation, adiposity, cardiorespiratory fitness, feelings of sadness, social relationships, and physical activity in adolescents. This was a cross-sectional study conducted with 1,152 Brazilian adolescents aged between 10 and 17 years. Somatic maturation was estimated through Mirwald's method (peak height velocity). Physical activity was assessed through Baecke questionnaire (occupational, leisure, and sport contexts). Body mass index, body fat (sum of skinfolds), cardiorespiratory fitness (20-m shuttle run test), self-perceptions of social relationship, and frequency of sadness feelings were obtained for statistical modeling. Somatic maturation is directly related to sport practice and leisure time physical activity only among girls (β=0.12, pmaturity and physical activity in boys and for occupational physical activity in girls. In general, models presented good fit coefficients. Biocultural model presents good fit and emotional/biological factors mediate part of the relationship between somatic maturation and physical activity. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  1. Centriole maturation requires regulated Plk1 activity during two consecutive cell cycles.

    Science.gov (United States)

    Kong, Dong; Farmer, Veronica; Shukla, Anil; James, Jana; Gruskin, Richard; Kiriyama, Shigeo; Loncarek, Jadranka

    2014-09-29

    Newly formed centrioles in cycling cells undergo a maturation process that is almost two cell cycles long before they become competent to function as microtubule-organizing centers and basal bodies. As a result, each cell contains three generations of centrioles, only one of which is able to form cilia. It is not known how this long and complex process is regulated. We show that controlled Plk1 activity is required for gradual biochemical and structural maturation of the centrioles and timely appendage assembly. Inhibition of Plk1 impeded accumulation of appendage proteins and appendage formation. Unscheduled Plk1 activity, either in cycling or interphase-arrested cells, accelerated centriole maturation and appendage and cilia formation on the nascent centrioles, erasing the age difference between centrioles in one cell. These findings provide a new understanding of how the centriole cycle is regulated and how proper cilia and centrosome numbers are maintained in the cells.

  2. Cholinesterase inhibitory activity and chemical constituents of Stenochlaena palustris fronds at two different stages of maturity

    Directory of Open Access Journals (Sweden)

    Nelson Jeng-Yeou Chear

    2016-04-01

    Full Text Available Stenochlaena palustris fronds are popular as a vegetable in Southeast Asia. The objectives of this study were to evaluate the anticholinesterase properties and phytochemical profiles of the young and mature fronds of this plant. Both types of fronds were found to have selective inhibitory effect against butyrylcholinesterase compared with acetylcholinesterase. However, different sets of compounds were responsible for their activity. In young fronds, an antibutyrylcholinesterase effect was observed in the hexane extract, which was comprised of a variety of aliphatic hydrocarbons, fatty acids, and phytosterols. In the mature fronds, inhibitory activity was observed in the methanol extract, which contained a series of kaempferol glycosides. Our results provided novel information concerning the ability of S. palustris to inhibit cholinesterase and its phytochemical profile. Further research to investigate the potential use of this plant against Alzheimer's disease is warranted, however, young and mature fronds should be distinguished due to their phytochemical differences.

  3. Interleukin-18 activates skeletal muscle AMPK and reduces weight gain and insulin resistance in mice

    DEFF Research Database (Denmark)

    Madsen, Birgitte Lindegaard; Matthews, Vance B; Brandt, Claus

    2013-01-01

    Circulating interleukin (IL)-18 is elevated in obesity, but paradoxically causes hypophagia. We hypothesized that IL-18 may attenuate high fat diet induced insulin resistance by activating AMP activated protein kinase (AMPK). We studied mice with a global deletion of the α isoform of the IL-18...... receptor (IL-18R(-/-)), fed a standard chow or high fat diet (HFD). We next performed gain of function experiments in skeletal muscle, in vitro, ex vivo and in vivo. We show that IL-18 is implicated in metabolic homeostasis, inflammation and insulin resistance via mechanisms involving the activation...

  4. The Rab-GTPase-activating protein TBC1D1 regulates skeletal muscle glucose metabolism

    DEFF Research Database (Denmark)

    Szekeres, Ferenc; Chadt, Alexandra; Tom, Robby Z

    2012-01-01

    The Rab-GTPase-activating protein TBC1D1 has emerged as a novel candidate involved in metabolic regulation. Our aim was to determine whether TBC1D1 is involved in insulin as well as energy-sensing signals controlling skeletal muscle metabolism. TBC1D1-deficient congenic B6.SJL-Nob1.10 (Nob1.10(SJL...... be explained partly by a 50% reduction in GLUT4 protein, since proximal signaling at the level of Akt, AMPK, and acetyl-CoA carboxylase (ACC) was unaltered. Paradoxically, in vivo insulin-stimulated 2-deoxyglucose uptake was increased in EDL and tibialis anterior muscle from TBC1D1-deficient mice......)) and wild-type littermates were studied. Glucose and insulin tolerance, glucose utilization, hepatic glucose production, and tissue-specific insulin-mediated glucose uptake were determined. The effect of insulin, AICAR, or contraction on glucose transport was studied in isolated skeletal muscle. Glucose...

  5. Resistance training for activity limitations in older adults with skeletal muscle function deficits: a systematic review

    Directory of Open Access Journals (Sweden)

    Papa EV

    2017-06-01

    Full Text Available Evan V Papa,1 Xiaoyang Dong,2 Mahdi Hassan1 1Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 2Department of Physical Therapy, University of North Texas Health Science Center, Fort Worth, TX, USA Abstract: Human aging results in a variety of changes to skeletal muscle. Sarcopenia is the age-associated loss of muscle mass and is one of the main contributors to musculoskeletal impairments in the elderly. Previous research has demonstrated that resistance training can attenuate skeletal muscle function deficits in older adults, however few articles have focused on the effects of resistance training on functional mobility. The purpose of this systematic review was to 1 present the current state of literature regarding the effects of resistance training on functional mobility outcomes for older adults with skeletal muscle function deficits and 2 provide clinicians with practical guidelines that can be used with seniors during resistance training, or to encourage exercise. We set forth evidence that resistance training can attenuate age-related changes in functional mobility, including improvements in gait speed, static and dynamic balance, and fall risk reduction. Older adults should be encouraged to participate in progressive resistance training activities, and should be admonished to move along a continuum of exercise from immobility, toward the recommended daily amounts of activity. Keywords: aging, strength training, sarcopenia, mobility, balance

  6. The influence of anaerobic muscle activity, maturation and season on the flesh quality of farmed turbot

    NARCIS (Netherlands)

    Roth, B.; Imsland, A.; Stien, L.H.; Schelvis-Smit, A.A.M.; Gunnarsson, S.; Foss, A.

    2010-01-01

    In order to test seasonal, rearing, maturing and anaerobic muscle activity effect on the flesh quality of turbot (Scophthalmus maximus) a total of 80 farmed turbot from three different strains from reared under natural or continuous light were killed by a percussive blow to the head in November

  7. Evaluation of skeletal maturity in North Indian subjects using an objective method based on cervical vertebral bone age and assessment of its reliability as compared to hand wrist radiographic method

    Directory of Open Access Journals (Sweden)

    Sandeep Kumar

    2016-01-01

    Full Text Available Aim: To evaluate the skeletal maturity objectively and assess the reliability and validity of this method in North Indian subjects. Materials and Methods: Sixty subjects (8-16 years were taken and divided into two groups of 30 males and 30 females. For each subject, cervical vertebral bone age (VA was evaluated by the objective method described by Mito et al., and bone age (BA was estimated by Grave and Brown method of hand wrist radiograph. Correlations and average differences between various ages were determined. An analysis of variance and Tukey′s post-hoc tests were used to compare various ages at 5% significance level. Results: The correlations between cervical VAs and BAs were higher than other ages and also more in females than males. The analysis of female data showed no statistically significant difference (P > 0.05 whereas analysis of male data showed statistically significant difference (P < 0.05 between various ages. Conclusion: The findings of the present study suggest that this method of objectively evaluating skeletal maturation is reliable and can be applied to North Indian females only. The development of a new method to objectively evaluate cervical VA in males is needed.

  8. Skeletal Muscle Fibre-Specific Knockout of p53 Does Not Reduce Mitochondrial Content or Enzyme Activity

    Directory of Open Access Journals (Sweden)

    Ben Stocks

    2017-12-01

    Full Text Available Tumour protein 53 (p53 has been implicated in the regulation of mitochondrial biogenesis in skeletal muscle, with whole-body p53 knockout mice displaying impairments in basal mitochondrial content, respiratory capacity, and enzyme activity. This study aimed to determine the effect of skeletal muscle-specific loss of p53 on mitochondrial content and enzyme activity. Mitochondrial protein content, enzyme activity and mRNA profiles were assessed in skeletal muscle of 8-week-old male muscle fibre-specific p53 knockout mice (p53 mKO and floxed littermate controls (WT under basal conditions. p53 mKO and WT mice displayed similar content of electron transport chain proteins I-V and citrate synthase enzyme activity in skeletal muscle. In addition, the content of proteins regulating mitochondrial morphology (MFN2, mitofillin, OPA1, DRP1, FIS1, fatty acid metabolism (β-HAD, ACADM, ACADL, ACADVL, carbohydrate metabolism (HKII, PDH, energy sensing (AMPKα2, AMPKβ2, and gene transcription (NRF1, PGC-1α, and TFAM were comparable in p53 mKO and WT mice (p > 0.05. Furthermore, p53 mKO mice exhibited normal mRNA profiles of targeted mitochondrial, metabolic and transcriptional proteins (p > 0.05. Thus, it appears that p53 expression in skeletal muscle fibres is not required to develop or maintain mitochondrial protein content or enzyme function in skeletal muscle under basal conditions.

  9. Denervation-Induced Activation of the Ubiquitin-Proteasome System Reduces Skeletal Muscle Quantity Not Quality.

    Science.gov (United States)

    Baumann, Cory W; Liu, Haiming M; Thompson, LaDora V

    2016-01-01

    It is well known that the ubiquitin-proteasome system is activated in response to skeletal muscle wasting and functions to degrade contractile proteins. The loss of these proteins inevitably reduces skeletal muscle size (i.e., quantity). However, it is currently unknown whether activation of this pathway also affects function by impairing the muscle's intrinsic ability to produce force (i.e., quality). Therefore, the purpose of this study was twofold, (1) document how the ubiquitin-proteasome system responds to denervation and (2) identify the physiological consequences of these changes. To induce soleus muscle atrophy, C57BL6 mice underwent tibial nerve transection of the left hindlimb for 7 or 14 days (n = 6-8 per group). At these time points, content of several proteins within the ubiquitin-proteasome system were determined via Western blot, while ex vivo whole muscle contractility was specifically analyzed at day 14. Denervation temporarily increased several key proteins within the ubiquitin-proteasome system, including the E3 ligase MuRF1 and the proteasome subunits 19S, α7 and β5. These changes were accompanied by reductions in absolute peak force and power, which were offset when expressed relative to physiological cross-sectional area. Contrary to peak force, absolute and relative forces at submaximal stimulation frequencies were significantly greater following 14 days of denervation. Taken together, these data represent two keys findings. First, activation of the ubiquitin-proteasome system is associated with reductions in skeletal muscle quantity rather than quality. Second, shortly after denervation, it appears the muscle remodels to compensate for the loss of neural activity via changes in Ca2+ handling.

  10. Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1

    International Nuclear Information System (INIS)

    Park, In-Hyun; Erbay, Ebru; Nuzzi, Paul; Chen Jie

    2005-01-01

    The protein kinase mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation and growth, with the ribosomal subunit S6 kinase 1 (S6K1) as one of the key downstream signaling effectors. A critical role of mTOR signaling in skeletal muscle differentiation has been identified recently, and an unusual regulatory mechanism independent of mTOR kinase activity and S6K1 is revealed. An mTOR pathway has also been reported to regulate skeletal muscle hypertrophy, but the regulatory mechanism is not completely understood. Here, we report the investigation of mTOR's function in insulin growth factor I (IGF-I)-induced C2C12 myotube hypertrophy. Added at a later stage when rapamycin no longer had any effect on normal myocyte differentiation, rapamycin completely blocked myocyte hypertrophy as measured by myotube diameter. Importantly, a concerted increase of average myonuclei per myotube was observed in IGF-I-stimulated myotubes, which was also inhibited by rapamycin added at a time when it no longer affected normal differentiation. The mTOR protein level, its catalytic activity, its phosphorylation on Ser2448, and the activity of S6K1 were all found increased in IGF-I-stimulated myotubes compared to unstimulated myotubes. Using C2C12 cells stably expressing rapamycin-resistant forms of mTOR and S6K1, we provide genetic evidence for the requirement of mTOR and its downstream effector S6K1 in the regulation of myotube hypertrophy. Our results suggest distinct mTOR signaling mechanisms in different stages of skeletal muscle development: While mTOR regulates the initial myoblast differentiation in a kinase-independent and S6K1-independent manner, the hypertrophic function of mTOR requires its kinase activity and employs S6K1 as a downstream effector

  11. Activation of skeletal muscle AMPK promotes glucose disposal and glucose lowering in non-human primates and mice

    DEFF Research Database (Denmark)

    Cokorinos, Emily C; Delmore, Jake; Reyes, Allan R

    2017-01-01

    The AMP-activated protein kinase (AMPK) is a potential therapeutic target for metabolic diseases based on its reported actions in the liver and skeletal muscle. We evaluated two distinct direct activators of AMPK: a non-selective activator of all AMPK complexes, PF-739, and an activator selective...

  12. Nitric oxide and Na,K-ATPase activity in rat skeletal muscle.

    Science.gov (United States)

    Juel, C

    2016-04-01

    It has been suggested that nitric oxide (NO) stimulates the Na,K-ATPase in cardiac myocytes. Therefore, the aims of this study were to investigate whether NO increases Na,K-ATPase activity in skeletal muscle and, if that is the case, to identify the underlying mechanism. The study used isolated rat muscle, muscle homogenates and purified membranes as model systems. Na,K-ATPase activity was quantified from phosphate release due to ATP hydrolysis. Exposure to the NO donor spermine NONOate (10 μm) increased the maximal Na,K-ATPase activity by 27% in isolated glycolytic muscles, but had no effect in oxidative muscles. Spermine NONOate increased the maximal Na,K-ATPase activity by 58% (P Na,K-ATPase α-isoform. Incubation with cGMP (1 mm) increased the maximal Na,K-ATPase activity in homogenates from glycolytic muscle by 16% (P Na,K-ATPase in glycolytic skeletal muscle. Direct S-nitrosylation and interference with S-glutathionylation seem to be excluded. In addition, phosphorylation of phospholemman at serine 68 is not involved. Most likely, the NO/cGMP/protein kinase G signalling pathway is involved. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  13. Serum Is Not Necessary for Prior Pharmacological Activation of AMPK to Increase Insulin Sensitivity of Mouse Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Nicolas O. Jørgensen

    2018-04-01

    Full Text Available Exercise, contraction, and pharmacological activation of AMP-activated protein kinase (AMPK by 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR have all been shown to increase muscle insulin sensitivity for glucose uptake. Intriguingly, improvements in insulin sensitivity following contraction of isolated rat and mouse skeletal muscle and prior AICAR stimulation of isolated rat skeletal muscle seem to depend on an unknown factor present in serum. One study recently questioned this requirement of a serum factor by showing serum-independency with muscle from old rats. Whether a serum factor is necessary for prior AICAR stimulation to increase insulin sensitivity of mouse skeletal muscle is not known. Therefore, we investigated the necessity of serum for this effect of AICAR in mouse skeletal muscle. We found that the ability of prior AICAR stimulation to improve insulin sensitivity of mouse skeletal muscle did not depend on the presence of serum during AICAR stimulation. Although prior AICAR stimulation did not enhance proximal insulin signaling, insulin-stimulated phosphorylation of Tre-2/BUB2/CDC16- domain family member 4 (TBC1D4 Ser711 was greater in prior AICAR-stimulated muscle compared to all other groups. These results imply that the presence of a serum factor is not necessary for prior AMPK activation by AICAR to enhance insulin sensitivity of mouse skeletal muscle.

  14. Time course in calpain activity and autolysis in slow and fast skeletal muscle during clenbuterol treatment.

    Science.gov (United States)

    Douillard, Aymeric; Galbes, Olivier; Rossano, Bernadette; Vernus, Barbara; Bonnieu, Anne; Candau, Robin; Py, Guillaume

    2011-02-01

    Calpains are Ca2+ cysteine proteases that have been proposed to be involved in the cytoskeletal remodeling and wasting of skeletal muscle. Cumulative evidence also suggests that β2-agonists can lead to skeletal muscle hypertrophy through a mechanism probably related to calcium-dependent proteolytic enzyme. The aim of our study was to monitor calpain activity as a function of clenbuterol treatment in both slow and fast phenotype rat muscles. For this purpose, for 21 days we followed the time course of the calpain activity and of the ubiquitous calpain 1 and 2 autolysis, as well as muscle remodeling in the extensor digitorum longus (EDL) and soleus muscles of male Wistar rats treated daily with clenbuterol (4 mg·kg-1). A slow to fast fiber shift was observed in both the EDL and soleus muscles after 9 days of treatment, while hypertrophy was observed only in EDL after 9 days of treatment. Soleus muscle but not EDL muscle underwent an early apoptonecrosis phase characterized by hematoxylin and eosin staining. Total calpain activity was increased in both the EDL and soleus muscles of rats treated with clenbuterol. Moreover, calpain 1 autolysis increased significantly after 14 days in the EDL, but not in the soleus. Calpain 2 autolysis increased significantly in both muscles 6 hours after the first clenbuterol injection, indicating that clenbuterol-induced calpain 2 autolysis occurred earlier than calpain 1 autolysis. Together, these data suggest a preferential involvement of calpain 2 autolysis compared with calpain 1 autolysis in the mechanisms underlying the clenbuterol-induced skeletal muscle remodeling.

  15. Skeletal muscle mitochondrial respiration in AMPKa2 kinase dead mice

    DEFF Research Database (Denmark)

    Larsen, Steen; Kristensen, Jonas Møller; Stride, Nis

    2012-01-01

    AIM: To study if the phenotypical characteristics (exercise intolerance; reduced spontaneous activity) of the AMPKa2 kinase-dead (KD) mice can be explained by a reduced mitochondrial respiratory flux rates (JO(2) ) in skeletal muscle. Secondly, the effect of the maturation process on JO(2...

  16. Role of 5'AMP-activated protein kinase in skeletal muscle

    DEFF Research Database (Denmark)

    Treebak, Jonas Thue; Wojtaszewski, Jørgen F. P.

    2008-01-01

    5'AMP-activated protein kinase (AMPK) is recognized as an important intracellular energy sensor, shutting down energy-consuming processes and turning on energy-generating processes. Discovery of target proteins of AMPK has dramatically increased in the past 10 years. Historically, AMPK was first...... shown to regulate fatty acid and cholesterol synthesis, but is now hypothesized to take part in the regulation of energy/fuel balance not only at the cellular level but also at the level of the whole organism. In this brief review we will discuss some of the roles of AMPK in skeletal muscle....

  17. Roles of Notch1 Signaling in Regulating Satellite Cell Fates Choices and Postnatal Skeletal Myogenesis.

    Science.gov (United States)

    Shan, Tizhong; Xu, Ziye; Wu, Weiche; Liu, Jiaqi; Wang, Yizhen

    2017-11-01

    Adult skeletal muscle stem cells, also called satellite cells, are indispensable for the growth, maintenance, and regeneration of the postnatal skeletal muscle. Satellite cells, predominantly quiescent in mature resting muscles, are activated after skeletal muscle injury or degeneration. Notch1 signaling is an evolutionarily conserved pathway that plays crucial roles in satellite cells homeostasis and postnatal skeletal myogenesis and regeneration. Activation of Notch1 signaling promotes the muscle satellite cells quiescence and proliferation, but inhibits differentiation of muscle satellite cells. Notably, the new roles of Notch1 signaling during late-stage of skeletal myogenesis including in post-differentiation myocytes and post-fusion myotubes have been recently reported. Here, we mainly review and discuss the regulatory roles of Notch1 in regulating satellite cell fates choices and skeletal myogenesis. J. Cell. Physiol. 232: 2964-2967, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Dendritic cell activation and maturation induced by recombinant calreticulin fragment 39-272.

    Science.gov (United States)

    Li, Yue; Zeng, Xiaoli; He, Lijuan; Yuan, Hui

    2015-01-01

    Dendritic cells (DC) are the most potent antigen-presenting cells for initiating immune responses. DC maturation can be induced by exposing of immature DC to pathogen products or pro-inflammatory factor, which dramatically enhances the ability of DC to activate Ag-specific T cells. In this study, a recombinant calreticulin fragment 39-272 (rCRT/39-272) covering the lectin-like N domain and partial P domain of murine CRT has been expressed and purified in Escherichia coli. Functional analysis studies revealed that rCRT/39-272 has potent immunostimulatory activities in both activating human monocytes and B cells to secrete cytokines. rCRT/39-272 can drive the activation of bone marrow derived DC in TLR4/CD14 dependent way, as indicated by secretion of cytokines IL-12/IL-23 (p40) and IL-1β. Exposure of DC to rCRT/39-272 induces P-Akt, suggesting that rCRT/39-272 induces maturation of DC through PI3K/Akt signaling pathway. The results suggest that soluble rCRT/39-272 is a potent stimulatory agent to DC maturation in TLR4/CD14 and PI3K/Akt dependent pathway. It may play important roles in initiating cellular immunity in vivo and the T cell response in vitro. Thus it could be used for study of DC-based tumor vaccines.

  19. Catalase activity is modulated by calcium and calmodulin in detached mature leaves of sweet potato.

    Science.gov (United States)

    Afiyanti, Mufidah; Chen, Hsien-Jung

    2014-01-15

    Catalase (CAT) functions as one of the key enzymes in the scavenging of reactive oxygen species and affects the H2O2 homeostasis in plants. In sweet potato, a major catalase isoform was detected, and total catalase activity showed the highest level in mature leaves (L3) compared to immature (L1) and completely yellow, senescent leaves (L5). The major catalase isoform as well as total enzymatic activity were strongly suppressed by ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA). This inhibition could be specifically and significantly mitigated in mature L3 leaves by exogenous CaCl2, but not MgCl2 or CoCl2. EGTA also inhibited the activity of the catalase isoform in vitro. Furthermore, chlorpromazine (CPZ), a calmodulin (CAM) inhibitor, drastically suppressed the major catalase isoform as well as total enzymatic activity, and this suppression was alleviated by exogenous sweet potato calmodulin (SPCAM) fusion protein in L3 leaves. CPZ also inhibited the activity of the catalase isoform in vitro. Protein blot hybridization showed that both anti-catalase SPCAT1 and anti-calmodulin SPCAM antibodies detect a band at the same position, which corresponds to the activity of the major catalase isoform from unboiled, but not boiled crude protein extract of L3 leaves. An inverse correlation between the major catalase isoform/total enzymatic activity and the H2O2 level was also observed. These data suggest that sweet potato CAT activity is modulated by CaCl2 and SPCAM, and plays an important role in H2O2 homeostasis in mature leaves. Association of SPCAM with the major CAT isoform is required and regulates the in-gel CAT activity band. Copyright © 2013 Elsevier GmbH. All rights reserved.

  20. Expansão maxilar em adultos e adolescentes com maturação esquelética avançada Maxillary expansion in adults and adolescents with advanced skeletal maturation

    Directory of Open Access Journals (Sweden)

    Rowdley Robert Pereira Rossi

    2009-10-01

    Full Text Available A deficiência transversa da maxila é um fator agravante e complicador do tratamento ortodôntico em adultos. Sua correção ainda gera dúvidas e controvérsias entre clínicos e pesquisadores. O objetivo deste trabalho foi analisar e discutir fatores determinantes para o planejamento da expansão maxilar em adultos e adolescentes com maturação esquelética avançada. Ausências dentárias múltiplas, grandes inclinações dentoalveolares para vestibular, recessão gengival, perda óssea alveolar e mobilidade dos dentes posterossuperiores contraindicam a realização de expansão rápida da maxila em indivíduos adultos ou com maturação esquelética avançada. No entanto, esses fatores não devem ser considerados isoladamente para a escolha do método de expansão palatal nesses pacientes. Nessas situações, a Expansão Rápida da Maxila Assistida Cirurgicamente (ERMAC pode ser uma opção, entretanto, a escolha por essa técnica deve basear-se principalmente na idade do paciente, no grau de maturação esquelética, na localização da deficiência transversa da maxila e nas estruturas anatômicas que oferecem maior resistência à expansão maxilar. O Hyrax é o aparelho mais indicado para indivíduos que vão se submeter à ERMAC.The transverse maxillary deficiency is a complication factor in adults' orthodontic treatment. Its correction still generates doubts and controversies between clinicians and researchers. The aim of this paper is to discuss the determinative factors in planning maxillary expansion in adults and adolescents with advanced skeletal maturation. Multiple dental absences, several dentoalveolar buccal inclination, gingival recession, alveolar bone loss and mobility of posterosuperior teeth contraindicate the rapid maxillary expansion in adults or patients with advanced skeletal maturation. However, these factors should not be considered separately when choosing the method for palatal expansion in adults. In these

  1. Barley HvPAPhy_a as transgene provides high and stable phytase activities in mature barley straw and in grains

    DEFF Research Database (Denmark)

    Holme, Inger; Dionisio, Giuseppe; Madsen, Claus Krogh

    2017-01-01

    The phytase purple acid phosphatase (HvPAPhy_a) expressed during barley seed development was evaluated as transgene for overexpression in barley. The phytase was expressed constitutively driven by the cauliflower mosaic virus 35S-promoter, and the phytase activity was measured in the mature grains......, the green leaves and in the dry mature vegetative plant parts left after harvest of the grains. The T2-generation of HvPAPhy_a transformed barley showed phytase activity increases up to 19-fold (29 000 phytase units (FTU) per kg in mature grains). Moreover, also in green leaves and mature dry straw, phytase...... activities were increased significantly by 110-fold (52 000 FTU/kg) and 57-fold (51 000 FTU/kg), respectively. The HvPAPhy_a-transformed barley plants with high phytase activities possess triple potential utilities for the improvement of phosphate bioavailability. First of all, the utilization of the mature...

  2. Effects of sex pheromones and sexual maturation on locomotor activity in female sea lamprey (Petromyzon marinus)

    Science.gov (United States)

    Walaszczyk, Erin J.; Johnson, Nicholas S.; Steibel, Juan Pedro; Li, Weiming

    2013-01-01

    Synchronization of male and female locomotor rhythmicity can play a vital role in ensuring reproductive success. Several physiological and environmental factors alter these locomotor rhythms. As sea lamprey, Petromyzon marinus, progress through their life cycle, their locomotor activity rhythm changes multiple times. The goal of this study was to elucidate the activity patterns of adult female sea lamprey during the sexual maturation process and discern the interactions of these patterns with exposure to male pheromones. During these stages, preovulated and ovulated adult females are exposed to sex pheromone compounds, which are released by spermiated males and attract ovulated females to the nest for spawning. The locomotor behavior of adult females was monitored in a natural stream with a passive integrated tag responder system as they matured, and they were exposed to a sex pheromone treatment (spermiated male washings) or a control (prespermiated male washings). Results showed that, dependent on the hour of day, male sex pheromone compounds reduce total activity (p reproductive synchrony of mature adults, thus increasing reproductive success in this species.

  3. Polysaccharide purified from Ganoderma atrum induced activation and maturation of murine myeloid-derived dendritic cells.

    Science.gov (United States)

    Wang, Hui; Yu, Qiang; Nie, Shao-Ping; Xiang, Quan-Dan; Zhao, Ming-Ming; Liu, Shi-Yu; Xie, Ming-Yong; Wang, Shun-Qi

    2017-10-01

    Ganoderma atrum (G. atrum), a member of the genus Ganoderma, is an edible and medicinal fungus. In this study, we investigated the direct and indirect effects of G. atrum polysaccharide (PSG-1) on dendritic cells (DCs). Firstly, flow cytometric and ELISA analysis showed that PSG-1 increased cell surface molecule expression of MHC-II, CD80 and CD86, and enhanced the production of IL-12 p70, IL-6, IL-10, RANTES, MIP-1α and MCP-1 in DCs. PSG-1-treated DCs promoted the proliferation of splenic T lymphocyte of mouse in mixed lymphocyte reaction. The above results demonstrated that PSG-1 induced the maturation of DCs. Secondly, PSG-1 increased the phosphorylation of p38, ERK and JNK determined by western blot. Inhibitors of p38, ERK and JNK decreased PSG-1-induced expression of MHC-II, CD80 and CD86 and production of IL-6 and IL-10 by DCs. These results suggested that PSG-1 induced mitogen-activated protein kinase (MAPK) activation was involved in the regulation of maturation markers and cytokines expression in DCs. Finally, PSG-1 increased expression of MHC-II of DCs in a DCs-Caco-2 co-culture model, suggesting that PSG-1 could indirectly influence DCs. In summary, our data suggested that PSG-1 directly induced DCs maturation via activating MAPK pathways, and indirectly stimulated DCs separated by intestinal epithelial cells. Copyright © 2017. Published by Elsevier Ltd.

  4. Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytes.

    Science.gov (United States)

    Paco, Sonia; Hummel, Manuela; Plá, Virginia; Sumoy, Lauro; Aguado, Fernando

    2016-04-23

    cAMP signaling produces dramatic changes in astrocyte morphology and physiology. However, its involvement in phenotype acquisition and the transcriptionally mediated mechanisms of action are largely unknown. Here we analyzed the global transcriptome of cultured astroglial cells incubated with activators of cAMP pathways. A bulk of astroglial transcripts, 6221 annotated genes, were differentially regulated by cAMP signaling. cAMP analogs strongly upregulated genes involved in typical functions of mature astrocytes, such as homeostatic control, metabolic and structural support to neurons, antioxidant defense and communication, whereas they downregulated a considerable number of proliferating and immaturity-related transcripts. Moreover, numerous genes typically activated in reactive cells, such as scar components and immunological mediators, were repressed by cAMP. GSEA analysis contrasting gene expression profiles with transcriptome signatures of acutely isolated astrocytes and in situ evaluation of protein levels in these cells showed that cAMP signaling conferred mature and in vivo-like transcriptional features to cultured astrocytes. These results indicate that cAMP signaling is a key pathway promoting astrocyte maturation and restricting their developmental and activation features. Therefore, a positive modulation of cAMP signaling may promote the normal state of differentiated astrocytes and favor the protection and function of neuronal networks.

  5. Blockades of mitogen-activated protein kinase and calcineurin both change fibre-type markers in skeletal muscle culture

    DEFF Research Database (Denmark)

    Higginson, James; Wackerhage, Henning; Woods, Niall

    2002-01-01

    A and mitogen-activated protein kinase kinase (MEK1/2) blockade with U0126 upon myosin heavy chain (MHC) isoform mRNA levels and activities of metabolic enzymes after 1 day, 3 days and 7 days of treatment in primary cultures of spontaneously twitching rat skeletal muscle. U0126 treatment significantly decreased......Activation of either the calcineurin or the extracellular signal-regulated kinase (ERK1/2) pathway increases the percentage of slow fibres in vivo suggesting that both pathways can regulate fibre phenotypes in skeletal muscle. We investigated the effect of calcineurin blockade with cyclosporin...

  6. Effect of vanadate on glucose transporter (GLUT4) intrinsic activity in skeletal muscle plasma membrane giant vesicles

    DEFF Research Database (Denmark)

    Kristiansen, S; Youn, J; Richter, Erik

    1996-01-01

    of vanadate (NaVO3) on glucose transporter (GLUT4) intrinsic activity (V(max) = intrinsic activity x [GLUT4 protein]) was studied in muscle plasma membrane giant vesicles. Giant vesicles (average diameter 7.6 microns) were produced by collagenase treatment of rat skeletal muscle. The vesicles were incubated......) 55% and 60%, respectively, compared with control. The plasma membrane GLUT4 protein content was not changed in response to vanadate. It is concluded that vanadate decreased glucose transport per GLUT4 (intrinsic activity). This finding suggests that regulation of glucose transport in skeletal muscle...

  7. Plasticity of TOM complex assembly in skeletal muscle mitochondria in response to chronic contractile activity.

    Science.gov (United States)

    Joseph, Anna-Maria; Hood, David A

    2012-03-01

    We investigated the assembly of the TOM complex within skeletal muscle under conditions of chronic contractile activity-induced mitochondrial biogenesis. Tom40 import into mitochondria was increased by chronic contractile activity, as was its time-dependent assembly into the TOM complex. These changes coincided with contractile activity-induced augmentations in the expression of key protein import machinery components Tim17, Tim23, and Tom22, as well as the cytosolic chaperone Hsp90. These data indicate the adaptability of the TOM protein import complex and suggest a regulatory role for the assembly of this complex in exercise-induced mitochondrial biogenesis. Copyright © 2011 Elsevier B.V. and Mitochondria Research Society. All rights reserved. All rights reserved.

  8. Structure-Activity Relationships of the Human Immunodeficiency Virus Type 1 Maturation Inhibitor PF-46396.

    Science.gov (United States)

    Murgatroyd, Christopher; Pirrie, Lisa; Tran, Fanny; Smith, Terry K; Westwood, Nicholas J; Adamson, Catherine S

    2016-09-15

    HIV-1 maturation inhibitors are a novel class of antiretroviral compounds that consist of two structurally distinct chemical classes: betulinic acid derivatives and the pyridone-based compound PF-46396. It is currently believed that both classes act by similar modes of action to generate aberrant noninfectious particles via inhibition of CA-SP1 cleavage during Gag proteolytic processing. In this study, we utilized a series of novel analogues with decreasing similarity to PF-46396 to determine the chemical groups within PF-46396 that contribute to antiviral activity, Gag binding, and the relationship between these essential properties. A spectrum of antiviral activity (active, intermediate, and inactive) was observed across the analogue series with respect to CA-SP1 cleavage and HIV-1 (NL4-3) replication kinetics in Jurkat T cells. We demonstrate that selected inactive analogues are incorporated into wild-type (WT) immature particles and that one inactive analogue is capable of interfering with PF-46396 inhibition of CA-SP1 cleavage. Mutations that confer PF-46396 resistance can impose a defective phenotype on HIV-1 that can be rescued in a compound-dependent manner. Some inactive analogues retained the capacity to rescue PF-46396-dependent mutants (SP1-A3V, SP1-A3T, and CA-P157S), implying that they can also interact with mutant Gag. The structure-activity relationships observed in this study demonstrate that (i) the tert-butyl group is essential for antiviral activity but is not an absolute requirement for Gag binding, (ii) the trifluoromethyl group is optimal but not essential for antiviral activity, and (iii) the 2-aminoindan group is important for antiviral activity and Gag binding but is not essential, as its replacement is tolerated. Combinations of antiretroviral drugs successfully treat HIV/AIDS patients; however, drug resistance problems make the development of new mechanistic drug classes an ongoing priority. HIV-1 maturation inhibitors are novel as they

  9. Autophagic signaling and proteolytic enzyme activity in cardiac and skeletal muscle of spontaneously hypertensive rats following chronic aerobic exercise.

    Directory of Open Access Journals (Sweden)

    Elliott M McMillan

    Full Text Available Hypertension is a cardiovascular disease associated with deleterious effects in skeletal and cardiac muscle. Autophagy is a degradative process essential to muscle health. Acute exercise can alter autophagic signaling. Therefore, we aimed to characterize the effects of chronic endurance exercise on autophagy in skeletal and cardiac muscle of normotensive and hypertensive rats. Male Wistar Kyoto (WKY and spontaneously hypertensive rats (SHR were assigned to a sedentary condition or 6 weeks of treadmill running. White gastrocnemius (WG of hypertensive rats had higher (p<0.05 caspase-3 and proteasome activity, as well as elevated calpain activity. In addition, skeletal muscle of hypertensive animals had elevated (p<0.05 ATG7 and LC3I protein, LAMP2 mRNA, and cathepsin activity, indicative of enhanced autophagic signaling. Interestingly, chronic exercise training increased (p<0.05 Beclin-1, LC3, and p62 mRNA as well as proteasome activity, but reduced (p<0.05 Beclin-1 and ATG7 protein, as well as decreased (p<0.05 caspase-3, calpain, and cathepsin activity. Left ventricle (LV of hypertensive rats had reduced (p<0.05 AMPKα and LC3II protein, as well as elevated (p<0.05 p-AKT, p-p70S6K, LC3I and p62 protein, which collectively suggest reduced autophagic signaling. Exercise training had little effect on autophagy-related signaling factors in LV; however, exercise training increased (p<0.05 proteasome activity but reduced (p<0.05 caspase-3 and calpain activity. Our results suggest that autophagic signaling is altered in skeletal and cardiac muscle of hypertensive animals. Regular aerobic exercise can effectively alter the proteolytic environment in both cardiac and skeletal muscle, as well as influence several autophagy-related factors in skeletal muscle of normotensive and hypertensive rats.

  10. Role of adenosine 5'-monophosphate-activated protein kinase in interleukin-6 release from isolated mouse skeletal muscle

    DEFF Research Database (Denmark)

    Glund, Stephan; Treebak, Jonas Thue; Long, Yun Chau

    2009-01-01

    IL-6 is released from skeletal muscle during exercise and has consequently been implicated to mediate beneficial effects on whole-body metabolism. Using 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), a pharmacological activator of 5'-AMP-activated protein kinase (AMPK), we tested......-type mice was also incubated with the AMPK activator A-769662. Incubation of mouse glycolytic extensor digitorum longus and oxidative soleus muscle for 2 h was associated with profound IL-6 mRNA production and protein release, which was suppressed by AICAR (P ... the hypothesis that AMPK modulates IL-6 release from isolated muscle. Skeletal muscle from AMPKalpha2 kinase-dead transgenic, AMPKalpha1 knockout (KO) and AMPKgamma3 KO mice and respective wild-type littermates was incubated in vitro, in the absence or presence of 2 mmol/liter AICAR. Skeletal muscle from wild...

  11. Top 10 Research Questions Related to Growth and Maturation of Relevance to Physical Activity, Performance, and Fitness

    Science.gov (United States)

    Malina, Robert M.

    2014-01-01

    Growth, maturation, and development dominate the daily lives of children and adolescents for approximately the first 2 decades of life. Growth and maturation are biological processes, while development is largely a behavioral process. The 3 processes occur simultaneously and interact. They can be influenced by physical activity and also can…

  12. Maternal high fat diet alters skeletal muscle mitochondrial catalytic activity in adult male rat offspring.

    Directory of Open Access Journals (Sweden)

    Chantal Anne Pileggi

    2016-11-01

    Full Text Available A maternal high-fat (HF diet during pregnancy can lead to metabolic compromise such as insulin resistance in adult offspring. Skeletal muscle mitochondrial dysfunction is one mechanism contributing to metabolic impairments in insulin resistant states. Therefore, the present study aimed to investigate whether mitochondrial dysfunction is evident in metabolically compromised offspring born to HF-fed dams. Sprague-Dawley dams were randomly assigned to receive a purified control diet (CD; 10% kcal from fat or a high fat diet (HFD; 45% kcal from fat for 10 days prior to mating, throughout pregnancy and during lactation. From weaning, all male offspring received a standard chow diet and soleus muscle was collected at day 150. Expression of the mitochondrial transcription factors nuclear respiratory factor-1 (NRF1 and mitochondrial transcription factor A (mtTFA were downregulated in HF offspring. Furthermore, genes encoding the mitochondrial electron transport system (ETS respiratory complex subunits were supressed in HF offspring. Moreover, protein expression of the complex I subunit, NDUFB8, was downregulated in HF offspring (36%, which was paralleled by decreased maximal catalytic linked activity of complex I and III (40%. Together, these results indicate that exposure to a maternal HF diet during development may elicit lifelong mitochondrial alterations in offspring skeletal muscle.

  13. Gene expression profiling of porcine skeletal muscle in the early recovery phase following acute physical activity

    DEFF Research Database (Denmark)

    Hansen, Jeanette; Conley, Lene; Hedegaard, Jakob

    2012-01-01

    Acute physical activity elicits changes in gene expression in skeletal muscles to promote metabolic changes and to repair exercise-induced muscle injuries. In the present time-course study, pigs were submitted to an acute bout of treadmill running until near exhaustion to determine the impact...... associated with proteolytic events, such as the muscle-specific E3 ubiquitin ligase atrogin-1, were significantly upregulated, suggesting that protein breakdown, prevention of protein aggregation and stabilization of unfolded proteins are important processes for restoration of cellular homeostasis. We also...... detected an upregulation of genes that are associated with muscle cell proliferation and differentiation, including MUSTN1, ASB5 and CSRP3, possibly reflecting activation, differentiation and fusion of satellite cells to facilitate repair of muscle damage. In addition, exercise increased expression...

  14. G0/G1 Switch Gene 2 controls adipose triglyceride lipase activity and lipid metabolism in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Claire Laurens

    2016-07-01

    Full Text Available Objective: Recent data suggest that adipose triglyceride lipase (ATGL plays a key role in providing energy substrate from triglyceride pools and that alterations of its expression/activity relate to metabolic disturbances in skeletal muscle. Yet little is known about its regulation. We here investigated the role of the protein G0/G1 Switch Gene 2 (G0S2, recently described as an inhibitor of ATGL in white adipose tissue, in the regulation of lipolysis and oxidative metabolism in skeletal muscle. Methods: We first examined G0S2 protein expression in relation to metabolic status and muscle characteristics in humans. We next overexpressed and knocked down G0S2 in human primary myotubes to assess its impact on ATGL activity, lipid turnover and oxidative metabolism, and further knocked down G0S2 in vivo in mouse skeletal muscle. Results: G0S2 protein is increased in skeletal muscle of endurance-trained individuals and correlates with markers of oxidative capacity and lipid content. Recombinant G0S2 protein inhibits ATGL activity by about 40% in lysates of mouse and human skeletal muscle. G0S2 overexpression augments (+49%, p < 0.05 while G0S2 knockdown strongly reduces (−68%, p < 0.001 triglyceride content in human primary myotubes and mouse skeletal muscle. We further show that G0S2 controls lipolysis and fatty acid oxidation in a strictly ATGL-dependent manner. These metabolic adaptations mediated by G0S2 are paralleled by concomitant changes in glucose metabolism through the modulation of Pyruvate Dehydrogenase Kinase 4 (PDK4 expression (5.4 fold, p < 0.001. Importantly, downregulation of G0S2 in vivo in mouse skeletal muscle recapitulates changes in lipid metabolism observed in vitro. Conclusion: Collectively, these data indicate that G0S2 plays a key role in the regulation of skeletal muscle ATGL activity, lipid content and oxidative metabolism. Keywords: Lipid metabolism, Skeletal muscle, Lipolysis, Adipose triglyceride lipase

  15. Activation of Skeletal Muscle AMPK Promotes Glucose Disposal and Glucose Lowering in Non-human Primates and Mice.

    Science.gov (United States)

    Cokorinos, Emily C; Delmore, Jake; Reyes, Allan R; Albuquerque, Bina; Kjøbsted, Rasmus; Jørgensen, Nicolas O; Tran, Jean-Luc; Jatkar, Aditi; Cialdea, Katherine; Esquejo, Ryan M; Meissen, John; Calabrese, Matthew F; Cordes, Jason; Moccia, Robert; Tess, David; Salatto, Christopher T; Coskran, Timothy M; Opsahl, Alan C; Flynn, Declan; Blatnik, Matthew; Li, Wenlin; Kindt, Erick; Foretz, Marc; Viollet, Benoit; Ward, Jessica; Kurumbail, Ravi G; Kalgutkar, Amit S; Wojtaszewski, Jørgen F P; Cameron, Kimberly O; Miller, Russell A

    2017-05-02

    The AMP-activated protein kinase (AMPK) is a potential therapeutic target for metabolic diseases based on its reported actions in the liver and skeletal muscle. We evaluated two distinct direct activators of AMPK: a non-selective activator of all AMPK complexes, PF-739, and an activator selective for AMPK β1-containing complexes, PF-249. In cells and animals, both compounds were effective at activating AMPK in hepatocytes, but only PF-739 was capable of activating AMPK in skeletal muscle. In diabetic mice, PF-739, but not PF-249, caused a rapid lowering of plasma glucose levels that was diminished in the absence of skeletal muscle, but not liver, AMPK heterotrimers and was the result of an increase in systemic glucose disposal with no impact on hepatic glucose production. Studies of PF-739 in cynomolgus monkeys confirmed translation of the glucose lowering and established activation of AMPK in skeletal muscle as a potential therapeutic approach to treat diabetic patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Natural isothiocyanates express antimicrobial activity against developing and mature biofilms of Pseudomonas aeruginosa.

    Science.gov (United States)

    Kaiser, Stefan J; Mutters, Nico T; Blessing, Brigitte; Günther, Frank

    2017-06-01

    The antimicrobial properties of natural isothiocyanates (ITCs) found in plants such as nasturtium (Tropaeolum majus) and horseradish (Armoracia rusticana), and the need of new chemotherapeutic options for treatment of infections caused by multidrug-resistant and biofilm-forming Gram-negative bacteria such as Pseudomonas aeruginosa (Pa), led us to evaluate the effects of three major ITCs, allylisothiocyanate (AITC), benzylisothiocyanate (BITC), and phenylethyl-isothiocyanate (PEITC), and a mixture (ITCM) adapted to the ITC composition after release of active components out of natural sources. Out of 105Pa isolates 27 isolates with increased biofilm formation were selected for testing. The effects of ITCs on Pa were evaluated regarding (1) planktonic bacterial proliferation, (2) biofilm formation, (3) metabolic activity in mature biofilms, and (4) synergism of ITCs and antibiotics. (1) Each ITC had anti-Pa activity. Mean minimum inhibitory concentrations (MICs) were (μg/ml, mean±standard deviation): AITC 103±6.9; BITC, 2145±249; PEITC 29,423±1652; and ITCM, 140±5. (2) Treating bacteria with PEITC and ITCM in concentrations below the MIC significantly inhibited biofilm formation. Particularly, ITCM reduced biofilm mass and bacterial proliferation. (3) ITCs significantly inhibited metabolic activity in mature biofilms. (4) Combining ITCs with meropenem synergistically increased antimicrobial efficacy on Pa biofilms. ITCs represent a promising group of natural anti-infective compounds with activity against Pa biofilms. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Changes in calmodulin concentration and cyclic 3',5'-nucleotide phosphodiesterase activity in skeletal muscle of hyper- and hypothyroid rats.

    Science.gov (United States)

    Mano, T; Iwase, K; Yoshimochi, I; Sawai, Y; Oda, N; Nishida, Y; Mokuno, T; Kotake, M; Nakai, A; Hayakawa, N

    1995-08-01

    Hyper- and hypothyroid states occasionally induce skeletal muscle dysfunction i.e. periodic paralysis and thyroid myopathy. The etiology of these diseases remains unclear, but several findings suggest that the catecholamine-beta-receptor-cAMP system or other messenger systems are disturbed in these diseases. In this context, we evaluated changes in the cyclic 3',5'-nucleotide metabolic enzyme, cyclic 3',5'-nucleotide phosphodiesterase (PDE) and calmodulin concentrations in skeletal muscles of hyper- and hypothyroid rats. Activities of cyclic AMP-PDE were low in skeletal muscle both from hyper- and hypothyroid rats, and calmodulin concentration was high in hyperthyroid and low in hypothyroid rats, as compared with normal rats. DE-52 column chromatographic analysis showed that the cGMP hydrolytic activity in peak I and the cAMP hydrolytic activity in peak II were decreased in hypothyroid rats, whereas cAMP hydrolytic activity in peak III was unchanged. The cAMP hydrolytic activity in peak III was decreased in hyperthyroid rats, but the activities in peaks I and II were unchanged. These findings indicate that cAMP and calmodulin may have some role in skeletal muscle function in the hyperthyroid state, and that cAMP and calmodulin-dependent metabolism may be suppressed in the hypothyroid state.

  18. Oral glucose ingestion attenuates exercise-induced activation of 5'-AMP-activated protein kinase in human skeletal muscle

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Birk, Jesper Bratz; Klein, Ditte Kjærsgaard

    2006-01-01

    5'-AMP-activated protein kinase (AMPK) has been suggested to be a 'metabolic master switch' regulating various aspects of muscle glucose and fat metabolism. In isolated rat skeletal muscle, glucose suppresses the activity of AMPK and in human muscle glycogen loading decreases exercise-induced AMPK...... activation. We hypothesized that oral glucose ingestion during exercise would attenuate muscle AMPK activation. Nine male subjects performed two bouts of one-legged knee-extensor exercise at 60% of maximal workload. The subjects were randomly assigned to either consume a glucose containing drink or a placebo...... drink during the two trials. Muscle biopsies were taken from the vastus lateralis before and after 2 h of exercise. Plasma glucose was higher (6.0 +/- 0.2 vs. 4.9 +/- 0.1 mmol L-1, P

  19. Glutathione S-transferase activity in follicular fluid from women undergoing ovarian stimulation: role in maturation.

    Science.gov (United States)

    Meijide, Susana; Hernández, M Luisa; Navarro, Rosaura; Larreategui, Zaloa; Ferrando, Marcos; Ruiz-Sanz, José Ignacio; Ruiz-Larrea, M Begoña

    2014-10-01

    Female infertility involves an emotional impact for the woman, often leading to a state of anxiety and low self-esteem. The assisted reproduction techniques (ART) are used to overcome the problem of infertility. In a first step of the in vitro fertilization therapy women are subjected to an ovarian stimulation protocol to obtain mature oocytes, which will result in competent oocytes necessary for fertilization to occur. Ovarian stimulation, however, subjects the women to a high physical and psychological stress, thus being essential to improve ART and to find biomarkers of dysfunction and fertility. GSH is an important antioxidant, and is also used in detoxification reactions, catalysed by glutathione S-transferases (GST). In the present work, we have investigated the involvement of GST in follicular maturation. Patients with fertility problems and oocyte donors were recruited for the study. From each woman follicles at two stages of maturation were extracted at the preovulatory stage. Follicular fluid was separated from the oocyte by centrifugation and used as the enzyme source. GST activity was determined based on its conjugation with 3,4-dichloronitrobenzene and the assay was adapted to a 96-well microplate reader. The absorbance was represented against the incubation time and the curves were adjusted to linearity (R(2)>0.990). Results showed that in both donors and patients GST activity was significantly lower in mature oocytes compared to small ones. These results suggest that GST may play a role in the follicle maturation by detoxifying xenobiotics, thus contributing to the normal development of the oocyte. Supported by FIS/FEDER (PI11/02559), Gobierno Vasco (Dep. Educación, Universiades e Investigación, IT687-13), and UPV/EHU (CLUMBER UFI11/20 and PES13/58). The work was approved by the Ethics Committee of the UPV/EHU (CEISH/96/2011/RUIZLARREA), and performed according to the UPV/EHU and IVI-Bilbao agreement (Ref. 2012/01). Copyright © 2014. Published by

  20. To Establish the Validity of Dental Age Assessment using Nolla′s Method on Comparing with Skeletal Age assessed by Hand-Wrist Radiographs

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    Kiran Sachan

    2013-01-01

    Conclusion: Females were more advanced in skeletal maturation than males. Chronological age showed inconsistent correlation with dental and skeletal ages. It was concluded that canine calcification stages can also be used for assessing skeletal maturity.

  1. Differentiating maturational and training influences on fMRI activation during music processing.

    Science.gov (United States)

    Ellis, Robert J; Norton, Andrea C; Overy, Katie; Winner, Ellen; Alsop, David C; Schlaug, Gottfried

    2012-04-15

    Two major influences on how the brain processes music are maturational development and active musical training. Previous functional neuroimaging studies investigating music processing have typically focused on either categorical differences between "musicians versus nonmusicians" or "children versus adults." In the present study, we explored a cross-sectional data set (n=84) using multiple linear regression to isolate the performance-independent effects of age (5 to 33 years) and cumulative duration of musical training (0 to 21,000 practice hours) on fMRI activation similarities and differences between melodic discrimination (MD) and rhythmic discrimination (RD). Age-related effects common to MD and RD were present in three left hemisphere regions: temporofrontal junction, ventral premotor cortex, and the inferior part of the intraparietal sulcus, regions involved in active attending to auditory rhythms, sensorimotor integration, and working memory transformations of pitch and rhythmic patterns. By contrast, training-related effects common to MD and RD were localized to the posterior portion of the left superior temporal gyrus/planum temporale, an area implicated in spectrotemporal pattern matching and auditory-motor coordinate transformations. A single cluster in right superior temporal gyrus showed significantly greater activation during MD than RD. This is the first fMRI which has distinguished maturational from training effects during music processing. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Effects of Resistance Training on Matrix Metalloproteinase Activity in Skeletal Muscles and Blood Circulation During Aging

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    Ivo V. de Sousa Neto

    2018-03-01

    Full Text Available Aging is a complex, multifactorial process characterized by the accumulation of deleterious effects, including biochemical adaptations of the extracellular matrix (ECM. The purpose of this study was to investigate the effects of 12 weeks of resistance training (RT on metalloproteinase 2 (MMP-2 activity in skeletal muscles and, MMP-2 and MMP-9 activity in the blood circulation of young and old rats. Twenty-eight Wistar rats were randomly divided into four groups (n = 7 per group: young sedentary (YS; young trained (YT, old sedentary (OS, and old trained (OT. The stair climbing RT consisted of one training session every 2 other day, with 8–12 dynamic movements per climb. The animals were euthanized 48 h after the end of the experimental period. MMP-2 and MMP-9 activity was measured by zymography. There was higher active MMP-2 activity in the lateral gastrocnemius and flexor digitorum profundus muscles in the OT group when compared to the OS, YS, and YT groups (p ≤ 0.001. Moreover, there was higher active MMP-2 activity in the medial gastrocnemius muscle in the OT group when compared to the YS and YT groups (p ≤ 0.001. The YS group presented lower active MMP-2 activity in the soleus muscle than the YT, OS, OT groups (p ≤ 0.001. With respect to active MMP-2/9 activity in the bloodstream, the OT group displayed significantly reduced activity (p ≤ 0.001 when compared to YS and YT groups. In conclusion, RT up-regulates MMP-2 activity in aging muscles, while down-regulating MMP-2 and MMP-9 in the blood circulation, suggesting that it may be a useful tool for the maintenance of ECM remodeling.

  3. Influence of mature men way of life on highly intensive physical activity

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    O.B. Pryshva

    2017-04-01

    Full Text Available Highly intensive physical activity is the most effective for men’s health protection. In modern life conditions its level is insufficient. It requires organism’s appropriate physical activity, which is determined by way of life. Especially important it is before trainings. Purpose: to study special aspects of different intensity’s physical activity; of eating special food and sleeping regime of mature men before their highly intensive physical trainings. Material: in experiment men (n=26, age - 35-53years, who practice healthy life style and independent physical activity of high intensity, participated. We used bio-register Basis B1. Every day we registered: Peak - physical activity of different intensity; duration and quality of sleep; relative weight of consumed food. Besides, we calculated body mass index and physical condition. The study was conducted during 30 days in winter period. The following results were compared: indicators before not planned physical activity and average-monthly indicators. Results: Before arbitrary physical functioning we found in men: confident weakening of average intensity (by 9-11% and low intensity (by 10% physical activity; confident increase of consumed food’s relative weight (by 6.82%, vegetarian food (by 10.64% and raw food (by 7.61%; confident reduction of animal origin food (by 8.7%. No changes were found in duration and quality of sleep before highly intensive physical functioning. Conclusions: specific features of mature men’s way of life before their not planned highly intensive physical functioning are as follows: reduction of general physical activity; increase of consumed food. These factors facilitate energy accumulation in organism for its realization in highly intensive physical functioning the next day.

  4. An ethanol extract of Artemisia iwayomogi activates PPARδ leading to activation of fatty acid oxidation in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Si Young Cho

    Full Text Available Although Artemisia iwayomogi (AI has been shown to improve the lipid metabolism, its mode of action is poorly understood. In this study, a 95% ethanol extract of AI (95EEAI was identified as a potent ligand of peroxisome proliferator-activated receptorδ (PPARδ using ligand binding analysis and cell-based reporter assay. In cultured primary human skeletal muscle cells, treatment of 95EEAI increased expression of two important PPARδ-regulated genes, carnitine palmitoyl-transferase-1 (CPT1 and pyruvate dehydrogenase kinase isozyme 4 (PDK4, and several genes acting in lipid efflux and energy expenditure. Furthermore, 95EEAI stimulated fatty acid oxidation in a PPARδ-dependent manner. High-fat diet-induced obese mice model further indicated that administration of 95EEAI attenuated diet-induced obesity through the activation of fatty acid oxidation in skeletal muscle. These results suggest that a 95% ethanol extract of AI may have a role as a new functional food material for the prevention and/or treatment of hyperlipidermia and obesity.

  5. Effects of in vivo-like activation frequency on the length-dependent force generation of skeletal muscle fibre bundles

    NARCIS (Netherlands)

    Zuurbier, C. J.; Lee-de Groot, M. B.; van der Laarse, W. J.; Huijing, P. A.

    1998-01-01

    It is known that a range of firing frequencies can be observed during in vivo muscle activity, yet information is lacking as to how different in vivo-like frequencies may affect force generation of skeletal muscle. This study examined the effects of constant (CSF, constant within one contraction)

  6. The cell nuclei of skeletal muscle cells are transcriptionally active in hibernating edible dormice

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    Muller Sylviane

    2009-03-01

    Full Text Available Abstract Background Skeletal muscle is able to react in a rapid, dynamic way to metabolic and mechanical stimuli. In particular, exposure to either prolonged starvation or disuse results in muscle atrophy. At variance, in hibernating animals muscle atrophy may be scarce or absent after bouts of hibernation i.e., periods of prolonged (months inactivity and food deprivation, and muscle function is fully preserved at arousal. In this study, myocytes from the quadriceps muscle of euthermic and hibernating edible dormice were investigated by a combination of morphological, morphometrical and immunocytochemical analyses at the light and electron microscopy level. The focus was on cell nuclei and mitochondria, which are highly sensitive markers of changing metabolic rate. Results Findings presented herein demonstrate that: 1 the general histology of the muscle, inclusive of muscle fibre shape and size, and the ratio of fast and slow fibre types are not affected by hibernation; 2 the fine structure of cytoplasmic and nuclear constituents is similar in euthermia and hibernation but for lipid droplets, which accumulate during lethargy; 3 during hibernation, mitochondria are larger in size with longer cristae, and 4 myonuclei maintain the same amount and distribution of transcripts and transcription factors as in euthermia. Conclusion In this study we demonstrate that skeletal muscle cells of the hibernating edible dormouse maintain their structural and functional integrity in full, even after months in the nest. A twofold explanation for that is envisaged: 1 the maintenance, during hibernation, of low-rate nuclear and mitochondrial activity counterbalancing myofibre wasting, 2 the intensive muscle stimulation (shivering during periodic arousals in the nest, which would mimic physical exercise. These two factors would prevent muscle atrophy usually occurring in mammals after prolonged starvation and/or inactivity as a consequence of prevailing catabolism

  7. The role of the myosin ATPase activity in adaptive thermogenesis by skeletal muscle.

    Science.gov (United States)

    Cooke, Roger

    2011-03-01

    Resting skeletal muscle is a major contributor to adaptive thermogenesis, i.e., the thermogenesis that changes in response to exposure to cold or to overfeeding. The identification of the "furnace" that is responsible for increased heat generation in resting muscle has been the subject of a number of investigations. A new state of myosin, the super relaxed state (SRX), with a very slow ATP turnover rate has recently been observed in skeletal muscle (Stewart et al. in Proc Natl Acad Sci USA 107:430-435, 2010). Inhibition of the myosin ATPase activity in the SRX was suggested to be caused by binding of the myosin head to the core of the thick filament in a structural motif identified earlier by electron microscopy. To be compatible with the basal metabolic rate observed in vivo for resting muscle, most myosin heads would have to be in the SRX. Modulation of the population of this state, relative to the normal relaxed state, was proposed to be a major contributor to adaptive thermogenesis in resting muscle. Transfer of only 20% of myosin heads from the SRX into the normal relaxed state would cause muscle thermogenesis to double. Phosphorylation of the myosin regulatory light chain was shown to transfer myosin heads from the SRX into the relaxed state, which would increase thermogenesis. In particular, thermogenesis by myosin has been proposed to play a role in the dissipation of calories during overfeeding. Up-regulation of muscle thermogenesis by pharmaceuticals that target the SRX would provide new approaches to the treatment of obesity or high blood sugar levels.

  8. Activated protein synthesis and suppressed protein breakdown signaling in skeletal muscle of critically ill patients.

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    Jakob G Jespersen

    Full Text Available BACKGROUND: Skeletal muscle mass is controlled by myostatin and Akt-dependent signaling on mammalian target of rapamycin (mTOR, glycogen synthase kinase 3β (GSK3β and forkhead box O (FoxO pathways, but it is unknown how these pathways are regulated in critically ill human muscle. To describe factors involved in muscle mass regulation, we investigated the phosphorylation and expression of key factors in these protein synthesis and breakdown signaling pathways in thigh skeletal muscle of critically ill intensive care unit (ICU patients compared with healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: ICU patients were systemically inflamed, moderately hyperglycemic, received insulin therapy, and showed a tendency to lower plasma branched chain amino acids compared with controls. Using Western blotting we measured Akt, GSK3β, mTOR, ribosomal protein S6 kinase (S6k, eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1, and muscle ring finger protein 1 (MuRF1; and by RT-PCR we determined mRNA expression of, among others, insulin-like growth factor 1 (IGF-1, FoxO 1, 3 and 4, atrogin1, MuRF1, interleukin-6 (IL-6, tumor necrosis factor α (TNF-α and myostatin. Unexpectedly, in critically ill ICU patients Akt-mTOR-S6k signaling was substantially higher compared with controls. FoxO1 mRNA was higher in patients, whereas FoxO3, atrogin1 and myostatin mRNAs and MuRF1 protein were lower compared with controls. A moderate correlation (r2=0.36, p<0.05 between insulin infusion dose and phosphorylated Akt was demonstrated. CONCLUSIONS/SIGNIFICANCE: We present for the first time muscle protein turnover signaling in critically ill ICU patients, and we show signaling pathway activity towards a stimulation of muscle protein synthesis and a somewhat inhibited proteolysis.

  9. Correlation between dental maturity and cervical vertebral maturity.

    Science.gov (United States)

    Chen, Jianwei; Hu, Haikun; Guo, Jing; Liu, Zeping; Liu, Renkai; Li, Fan; Zou, Shujuan

    2010-12-01

    The aim of this study was to investigate the association between dental and skeletal maturity. Digital panoramic radiographs and lateral skull cephalograms of 302 patients (134 boys and 168 girls, ranging from 8 to 16 years of age) were examined. Dental maturity was assessed by calcification stages of the mandibular canines, first and second premolars, and second molars, whereas skeletal maturity was estimated by the cervical vertebral maturation (CVM) stages. The Spearman rank-order correlation coefficient was used to measure the association between CVM stage and dental calcification stage of individual teeth. The mean chronologic age of girls was significantly lower than that of boys in each CVM stage. The Spearman rank-order correlation coefficients between dental maturity and cervical vertebral maturity ranged from 0.391 to 0.582 for girls and from 0.464 to 0.496 for boys (P cervical vertebral maturation stage. The development of the mandibular second molar in females and that of the mandibular canine in males had the strongest correlations with cervical vertebral maturity. Therefore, it is practical to consider the relationship between dental and skeletal maturity when planning orthodontic treatment. Copyright © 2010 Mosby, Inc. All rights reserved.

  10. Voluntary resistance running wheel activity pattern and skeletal muscle growth in rats.

    Science.gov (United States)

    Legerlotz, Kirsten; Elliott, Bradley; Guillemin, Bernard; Smith, Heather K

    2008-06-01

    The aims of this study were to characterize the pattern of voluntary activity of young rats in response to resistance loading on running wheels and to determine the effects of the activity on the growth of six limb skeletal muscles. Male Sprague-Dawley rats (4 weeks old) were housed individually with a resistance running wheel (R-RUN, n = 7) or a conventional free-spinning running wheel (F-RUN, n = 6) or without a wheel, as non-running control animals (CON, n = 6). The torque required to move the wheel in the R-RUN group was progressively increased, and the activity (velocity, distance and duration of each bout) of the two running wheel groups was recorded continuously for 45 days. The R-RUN group performed many more, shorter and faster bouts of running than the F-RUN group, yet the mean daily distance was not different between the F-RUN (1.3 +/- 0.2 km) and R-RUN group (1.4 +/- 0.6 km). Only the R-RUN resulted in a significantly (P RUN and R-RUN led to a significantly greater wet mass relative to increase in body mass and muscle fibre cross-sectional area in the soleus muscle compared with CON. We conclude that the pattern of voluntary activity on a resistance running wheel differs from that on a free-spinning running wheel and provides a suitable model to induce physiological muscle hypertrophy in rats.

  11. Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity.

    Science.gov (United States)

    Chaillou, Thomas; Lanner, Johanna T

    2016-12-01

    Reduced oxygen (O 2 ) levels (hypoxia) are present during embryogenesis and exposure to altitude and in pathologic conditions. During embryogenesis, myogenic progenitor cells reside in a hypoxic microenvironment, which may regulate their activity. Satellite cells are myogenic progenitor cells localized in a local environment, suggesting that the O 2 level could affect their activity during muscle regeneration. In this review, we present the idea that O 2 levels regulate myogenesis and muscle regeneration, we elucidate the molecular mechanisms underlying myogenesis and muscle regeneration in hypoxia and depict therapeutic strategies using changes in O 2 levels to promote muscle regeneration. Severe hypoxia (≤1% O 2 ) appears detrimental for myogenic differentiation in vitro, whereas a 3-6% O 2 level could promote myogenesis. Hypoxia impairs the regenerative capacity of injured muscles. Although it remains to be explored, hypoxia may contribute to the muscle damage observed in patients with pathologies associated with hypoxia (chronic obstructive pulmonary disease, and peripheral arterial disease). Hypoxia affects satellite cell activity and myogenesis through mechanisms dependent and independent of hypoxia-inducible factor-1α. Finally, hyperbaric oxygen therapy and transplantation of hypoxia-conditioned myoblasts are beneficial procedures to enhance muscle regeneration in animals. These therapies may be clinically relevant to treatment of patients with severe muscle damage.-Chaillou, T. Lanner, J. T. Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity. © FASEB.

  12. Urease activity as an index for assessing the maturity of cow manure and wheat residue vermicomposts.

    Science.gov (United States)

    Sudkolai, Saber Tayebi; Nourbakhsh, Farshid

    2017-06-01

    The establishment of a reliable index is an essential need to assess the degree of stability and maturity of solid wastes vermicomposts. The objective of this study was to investigate the effects of vermicomposting process on some chemical (pH, EC, OC, TN, lignin and C:N ratio) and biochemical properties of the cow manure (CM) and wheat residue (WR). Results demonstrated that during vermicomposting process of CM and WR urease activity was highly correlated with the time of vermicomposting (r=-0.97 ∗∗ for CM and r=-0.99 ∗∗ for WR), and well able to show the stability of organic waste. The urease activity showed significant correlations with the C:N ratio during the vermicomposting of CM and WR (r=0.89 ∗ and r=0.93 ∗∗ respectively) therefore it can be considered as a reliable indicator for determining the maturity and stability of organic wastes during vermicomposting process. Copyright © 2017. Published by Elsevier Ltd.

  13. Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

    Science.gov (United States)

    Wu, Jing; Tao, Wei-Wei; Chong, Dan-Yang; Lai, Shan-Shan; Wang, Chuang; Liu, Qi; Zhang, Tong-Yu; Xue, Bin; Li, Chao-Jun

    2018-03-15

    Postprandial insulin desensitization plays a critical role in maintaining whole-body glucose homeostasis by avoiding the excessive absorption of blood glucose; however, the detailed mechanisms that underlie how the major player, skeletal muscle, desensitizes insulin action remain to be elucidated. Herein, we report that early growth response gene-1 ( Egr-1) is activated by insulin in skeletal muscle and provides feedback inhibition that regulates insulin sensitivity after a meal. The inhibition of the transcriptional activity of Egr-1 enhanced the phosphorylation of the insulin receptor (InsR) and Akt, thus increasing glucose uptake in L6 myotubes after insulin stimulation, whereas overexpression of Egr-1 decreased insulin sensitivity. Furthermore, deletion of Egr-1 in the skeletal muscle improved systemic insulin sensitivity and glucose tolerance, which resulted in lower blood glucose levels after refeeding. Mechanistic analysis demonstrated that EGR-1 inhibited InsR phosphorylation and glucose uptake in skeletal muscle by binding to the proximal promoter region of protein tyrosine phosphatase-1B (PTP1B) and directly activating transcription. PTP1B knockdown largely restored insulin sensitivity and enhanced glucose uptake, even under conditions of EGR-1 overexpression. Our results indicate that EGR-1/PTP1B signaling negatively regulates postprandial insulin sensitivity and suggest a potential therapeutic target for the prevention and treatment of excessive glucose absorption.-Wu, J., Tao, W.-W., Chong, D.-Y., Lai, S.-S., Wang, C., Liu, Q., Zhang, T.-Y., Xue, B., Li, C.-J. Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

  14. Glucocorticoids activate the ATP-ubiquitin-dependent proteolytic system in skeletal muscle during fasting

    Science.gov (United States)

    Wing, S. S.; Goldberg, A. L.; Goldberger, A. L. (Principal Investigator)

    1993-01-01

    Glucocorticoids are essential for the increase in protein breakdown in skeletal muscle normally seen during fasting. To determine which proteolytic pathway(s) are activated upon fasting, leg muscles from fed and fasted normal rats were incubated under conditions that block or activate different proteolytic systems. After food deprivation (1 day), the nonlysosomal ATP-dependent process increased by 250%, as shown in experiments involving depletion of muscle ATP. Also, the maximal capacity of the lysosomal process increased 60-100%, but no changes occurred in the Ca(2+)-dependent or the residual energy-independent proteolytic processes. In muscles from fasted normal and adrenalectomized (ADX) rats, the protein breakdown sensitive to inhibitors of the lysosomal or Ca(2+)-dependent pathways did not differ. However, the ATP-dependent process was 30% slower in muscles from fasted ADX rats. Administering dexamethasone to these animals or incubating their muscles with dexamethasone reversed this defect. During fasting, when the ATP-dependent process rises, muscles show a two- to threefold increase in levels of ubiquitin (Ub) mRNA. However, muscles of ADX animals failed to show this response. Injecting dexamethasone into the fasted ADX animals increased muscle Ub mRNA within 6 h. Thus glucocorticoids activate the ATP-Ub-dependent proteolytic pathway in fasting apparently by enhancing the expression of components of this system such as Ub.

  15. Apoptosis may determine the release of skeletal alkaline phosphatase activity from human osteoblast-line cells.

    Science.gov (United States)

    Farley, J R; Stilt-Coffing, B

    2001-01-01

    Although quantitative measurement of skeletal alkaline phosphatase (sALP) activity in serum can provide an index of the rate of bone formation, the metabolic process that determines the release of sALP - from the surface of osteoblasts, into circulation-is unknown. The current studies were intended to examine the hypothesis that the release of sALP from human osteoblasts is a consequence of apoptotic cell death. We measured the release of sALP activity from human osteosarcoma (SaOS-2) cells and normal human bone cells, under basal conditions and in response to agents that increased apoptosis (TNF-a, okadiac acid) and agents that inhibit apoptosis (IGF-I, calpain, and caspase inhibitors). Apoptosis was determined by the presence of nucleosomes (histone-associated DNA) in the cytoplasm of the cells by using a commercial kit. The results of these studies showed that TNF-a and okadiac acid caused dose- and time-dependent increases in apoptosis in the SaOS-2 cells (r = 0.78 for doses of TNF-a and r = 0.93 for doses of okadiac acid, P sALP activity (e.g., r = 0.89 for TNF-a and r = 0.75 for okadiac acid, P sALP activity (P sALP activity (P sALP release. The associations between apoptosis and sALP release were not unique to osteosarcoma (i.e., SaOS-2) cells, but also seen with osteoblast-line cells derived from normal human bone. Together, these data demonstrate that the release of sALP activity from human osteoblast-line cells in vitro is associated with, and may be a consequence of, apoptotic cell death. These findings are consistent with the general hypothesis that the appearance of sALP activity in serum may reflect the turnover of osteoblast-line cells.

  16. Angiotensin II receptor blocker telmisartan enhances running endurance of skeletal muscle through activation of the PPAR-δ/AMPK pathway.

    Science.gov (United States)

    Feng, Xiaoli; Luo, Zhidan; Ma, Liqun; Ma, Shuangtao; Yang, Dachun; Zhao, Zhigang; Yan, Zhencheng; He, Hongbo; Cao, Tingbing; Liu, Daoyan; Zhu, Zhiming

    2011-07-01

    Clinical trials have shown that angiotensin II receptor blockers reduce the new onset of diabetes in hypertensives; however, the underlying mechanisms remain unknown. We investigated the effects of telmisartan on peroxisome proliferator activated receptor γ (PPAR-δ) and the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway in cultured myotubes, as well as on the running endurance of wild-type and PPAR-δ-deficient mice. Administration of telmisartan up-regulated levels of PPAR-δ and phospho-AMPKα in cultured myotubes. However, PPAR-δ gene deficiency completely abolished the telmisartan effect on phospho-AMPKαin vitro. Chronic administration of telmisartan remarkably prevented weight gain, enhanced running endurance and post-exercise oxygen consumption, and increased slow-twitch skeletal muscle fibres in wild-type mice, but these effects were absent in PPAR-δ-deficient mice. The mechanism is involved in PPAR-δ-mediated stimulation of the AMPK pathway. Compared to the control mice, phospho-AMPKα level in skeletal muscle was up-regulated in mice treated with telmisartan. In contrast, phospho-AMPKα expression in skeletal muscle was unchanged in PPAR-δ-deficient mice treated with telmisartan. These findings highlight the ability of telmisartan to improve skeletal muscle function, and they implicate PPAR-δ as a potential therapeutic target for the prevention of type 2 diabetes. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  17. Chronic alcohol consumption enhances iNKT cell maturation and activation

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hui, E-mail: hzhang@wsu.edu; Zhang, Faya; Zhu, Zhaohui; Luong, Dung; Meadows, Gary G.

    2015-01-15

    Alcohol consumption exhibits diverse effects on different types of immune cells. NKT cells are a unique T cell population and play important immunoregulatory roles in different types of immune responses. The effects of chronic alcohol consumption on NKT cells remain to be elucidated. Using a mouse model of chronic alcohol consumption, we found that alcohol increases the percentage of NKT cells, especially iNKT cells in the thymus and liver, but not in the spleen or blood. Alcohol consumption decreases the percentage of NK1.1{sup −} iNKT cells in the total iNKT cell population in all of the tissues and organs examined. In the thymus, alcohol consumption increases the number of NK1.1{sup +}CD44{sup hi} mature iNKT cells but does not alter the number of NK1.1{sup −} immature iNKT cells. A BrdU incorporation assay shows that alcohol consumption increases the proliferation of thymic NK1.1{sup −} iNKT cells, especially the NK1.1{sup −}CD44{sup lo} Stage I iNKT cells. The percentage of NKG2A{sup +} iNKT cells increases in all of the tissues and organs examined; whereas CXCR3{sup +} iNKT cells only increases in the thymus of alcohol-consuming mice. Chronic alcohol consumption increases the percentage of IFN-γ-producing iNKT cells and increases the blood concentration of IFN-γ and IL-12 after in vivo α-galactosylceramide (αGalCer) stimulation. Consistent with the increased cytokine production, the in vivo activation of iNKT cells also enhances the activation of dendritic cells (DC) and NK, B, and T cells in the alcohol-consuming mice. Taken together the data indicate that chronic alcohol consumption enhances iNKT cell maturation and activation, which favors the Th1 immune response. - Highlights: • Chronic alcohol consumption increases iNKT cells in the thymus and liver • Chronic alcohol consumption enhances thymic Stage I iNKT cell proliferation • Chronic alcohol consumption enhances iNKT cell maturation in thymus and periphery • Chronic alcohol

  18. Chronic alcohol consumption enhances iNKT cell maturation and activation

    International Nuclear Information System (INIS)

    Zhang, Hui; Zhang, Faya; Zhu, Zhaohui; Luong, Dung; Meadows, Gary G.

    2015-01-01

    Alcohol consumption exhibits diverse effects on different types of immune cells. NKT cells are a unique T cell population and play important immunoregulatory roles in different types of immune responses. The effects of chronic alcohol consumption on NKT cells remain to be elucidated. Using a mouse model of chronic alcohol consumption, we found that alcohol increases the percentage of NKT cells, especially iNKT cells in the thymus and liver, but not in the spleen or blood. Alcohol consumption decreases the percentage of NK1.1 − iNKT cells in the total iNKT cell population in all of the tissues and organs examined. In the thymus, alcohol consumption increases the number of NK1.1 + CD44 hi mature iNKT cells but does not alter the number of NK1.1 − immature iNKT cells. A BrdU incorporation assay shows that alcohol consumption increases the proliferation of thymic NK1.1 − iNKT cells, especially the NK1.1 − CD44 lo Stage I iNKT cells. The percentage of NKG2A + iNKT cells increases in all of the tissues and organs examined; whereas CXCR3 + iNKT cells only increases in the thymus of alcohol-consuming mice. Chronic alcohol consumption increases the percentage of IFN-γ-producing iNKT cells and increases the blood concentration of IFN-γ and IL-12 after in vivo α-galactosylceramide (αGalCer) stimulation. Consistent with the increased cytokine production, the in vivo activation of iNKT cells also enhances the activation of dendritic cells (DC) and NK, B, and T cells in the alcohol-consuming mice. Taken together the data indicate that chronic alcohol consumption enhances iNKT cell maturation and activation, which favors the Th1 immune response. - Highlights: • Chronic alcohol consumption increases iNKT cells in the thymus and liver • Chronic alcohol consumption enhances thymic Stage I iNKT cell proliferation • Chronic alcohol consumption enhances iNKT cell maturation in thymus and periphery • Chronic alcohol consumption induces Th1 immune response upon i

  19. AMP-activated protein kinase at the nexus of therapeutic skeletal muscle plasticity in Duchenne muscular dystrophy.

    Science.gov (United States)

    Ljubicic, Vladimir; Jasmin, Bernard J

    2013-10-01

    Recent studies have highlighted the potential of adenosine monophosphate-activated protein kinase (AMPK) to act as a central therapeutic target in Duchenne muscular dystrophy (DMD). Here, we review the role of AMPK as an important integrator of cell signaling pathways that mediate phenotypic plasticity within the context of dystrophic skeletal muscle. Pharmacological AMPK activation remodels skeletal muscle towards a slower, more oxidative phenotype, which is more pathologically resistant to the lack of dystrophin. Moreover, recent studies suggest that AMPK-activated autophagy may be beneficial for myofiber structure and function in mice with muscular dystrophy. Thus, AMPK may represent an ideal target for intervention because clinically approved pharmacological agonists exist, and because benefits can be derived via two independent yet, complementary biological pathways. The availability of several AMPK activators could therefore lead to the rapid development and implementation of novel and highly effective therapeutics aimed at altering the relentless progression of DMD. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Antioxidant Activity, Colour and Mineral Content Of Herbal Tea Prepared From Cosmos Caudatus Leaves at Different Maturity Stages

    International Nuclear Information System (INIS)

    Dian Nashiela Fatanah; Noriham Abdullah; Nooraain Hashim; Azizah Abd Hamid

    2016-01-01

    In recent years, increasing consumption of herbal tea is a worldwide trend because of their refreshing taste, positive potential health effect, convenience, abundant resources and also cheaper in price. However, different maturity stages of plants being used as raw material could affect the antioxidant activity, colour and mineral content in herbal tea. Thus, this present study was aimed at determining antioxidant activity, colour and mineral content of herbal tea prepared from Cosmos caudatus (C. caudatus) leaves at three different maturity stages namely young, mature and old. All prepared herbal tea were analysed for total phenolic content (TPC), total flavonoid content (TFC), ferric reducing antioxidant power (FRAP), 2-2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, colour and mineral content. The results demonstrated that herbal tea prepared from young leaves had strong (p<0.05) antioxidant activity compared to mature and old leaves for all assays tested. Pearsons correlation coefficient also revealed that TPC and TFC exhibited a strong positive correlation with reducing power but negatively correlated with DPPH scavenging activity indicating that these compounds are major contributors to the antioxidant activity. In fact, the darker (p<0.05) colour of C. caudatus herbal tea prepared from young leaves relates to their higher antioxidant activity as compared to mature and old leaves. However, C. caudatus herbal tea prepared from old leaves showed significantly higher in mineral content compared to mature and young leaves. Hence, it can be concluded that, as maturity increased, antioxidant activity and colour in C. caudatus herbal tea decreased and vice-versa for mineral content. (author)

  1. Antioxidant activity and total phenolic content of Moringa oleifera leaves in two stages of maturity.

    Science.gov (United States)

    Sreelatha, S; Padma, P R

    2009-12-01

    Antioxidants play an important role in inhibiting and scavenging free radicals, thus providing protection to human against infections and degenerative diseases. Current research is now directed towards natural antioxidants originated from plants due to safe therapeutics. Moringa oleifera is used in Indian traditional medicine for a wide range of various ailments. To understand the mechanism of pharmacological actions, antioxidant properties of the Moringa oleifera leaf extracts were tested in two stages of maturity using standard in vitro models. The successive aqueous extract of Moringa oleifera exhibited strong scavenging effect on 2, 2-diphenyl-2-picryl hydrazyl (DPPH) free radical, superoxide, nitric oxide radical and inhibition of lipid per oxidation. The free radical scavenging effect of Moringa oleifera leaf extract was comparable with that of the reference antioxidants. The data obtained in the present study suggests that the extracts of Moringa oleifera both mature and tender leaves have potent antioxidant activity against free radicals, prevent oxidative damage to major biomolecules and afford significant protection against oxidative damage.

  2. Indicadores de maduración esquelética y dental en pacientes de ortodoncia con menarquía Indicators of skeletal and dental maturation in orthodontics patients presenting menarche

    Directory of Open Access Journals (Sweden)

    Gladia Toledo Mayarí

    2012-03-01

    Full Text Available El propósito del presente trabajo fue determinar según la menarquía: la edad ósea, los estadios de maduración esquelética, los estadios de maduración de las vértebras cervicales y los estadios de calcificación del canino y el segundo premolar mandibulares izquierdos. Se realizó un estudio transversal y descriptivo en 30 pacientes femeninas con menarquía que ingresaron en la Clínica de Ortodoncia de la Facultad de Estomatología de La Habana, en el periodo comprendido entre abril de 2004 y septiembre de 2006. A cada paciente se le realizó una telerradiografía lateral de cráneo, una radiografía de la mano izquierda y una radiografía panorámica o periapical de la hemiarcada mandibular izquierda. En cada caso se evaluaron los métodos Taner-Whitehouse 2 (TW2, Grave y Brown, Hassel y Farman y Demirjian. Se estudiaron las variables: edad de aparición de la menarquía, edad ósea, edad cronológica, estadios de maduración esquelética, estadios de maduración de las vértebras cervicales, estadios de calcificación del canino y el segundo premolar mandibulares izquierdos. El promedio de la edad de aparición de la menarquía en esta muestra fue de 12,00 años con una desviación estándar de 1,00 año. Los promedios de la edad ósea fueron superiores a los de la edad cronológica en todos los grupos de edades. Las 30 pacientes estudiadas se encontraban en: estadios de maduración esquelética mayores que 4, estadios de maduración de las vértebras cervicales mayores que 1, estadio H de calcificación del canino mandibular izquierdo y estadios superiores al E para el segundo premolar mandibular izquierdo. En todos los métodos determinados se encontró que la mayoría de las pacientes con menarquía estaban en los estadios de maduración más avanzados.The aim of present paper was to determine according menarche the bone age, skeletal maturation stages, maturation stage of cervical vertebrae and the stages of calcification of canine

  3. Activity of daptomycin- and vancomycin-loaded poly-epsilon-caprolactone microparticles against mature staphylococcal biofilms

    Directory of Open Access Journals (Sweden)

    Santos Ferreira I

    2015-07-01

    Full Text Available Inês Santos Ferreira,1 Ana F Bettencourt,1 Lídia MD Gonçalves,1 Stefanie Kasper,2 Bertrand Bétrisey,3 Judith Kikhney,2 Annette Moter,2 Andrej Trampuz,4 António J Almeida1 1Research Institute for Medicines (iMed.ULisboa, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal; 2Biofilmcenter, German Heart Institute Berlin, Berlin, Germany; 3Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; 4Center for Musculoskeletal Surgery, Charité – University Medicine Berlin, Berlin, Germany Abstract: The aim of the present study was to develop novel daptomycin-loaded poly-epsilon-caprolactone (PCL microparticles with enhanced antibiofilm activity against mature biofilms of clinically relevant bacteria, methicillin-resistant Staphylococcus aureus (MRSA and polysaccharide intercellular adhesin-positive Staphylococcus epidermidis. Daptomycin was encapsulated into PCL microparticles by a double emulsion-solvent evaporation method. For comparison purposes, formulations containing vancomycin were also prepared. Particle morphology, size distribution, encapsulation efficiency, surface charge, thermal behavior, and in vitro release were assessed. All formulations exhibited a spherical morphology, micro­meter size, and negative surface charge. From a very early time stage, the released concentrations of daptomycin and vancomycin were higher than the minimal inhibitory concentration and continued so up to 72 hours. Daptomycin presented a sustained release profile with increasing concentrations of the drug being released up to 72 hours, whereas the release of vancomycin stabilized at 24 hours. The antibacterial activity of the microparticles was assessed by isothermal microcalorimetry against planktonic and sessile MRSA and S. epidermidis. Regarding planktonic bacteria, daptomycin-loaded PCL microparticles presented the highest antibacterial activity against both strains. Isothermal

  4. Baroreflex and neurovascular responses to skeletal muscle mechanoreflex activation in humans: an exercise in integrative physiology.

    Science.gov (United States)

    Drew, Rachel C

    2017-12-01

    Cardiovascular adjustments to exercise resulting in increased blood pressure (BP) and heart rate (HR) occur in response to activation of several neural mechanisms: the exercise pressor reflex, central command, and the arterial baroreflex. Neural inputs from these feedback and feedforward mechanisms integrate in the cardiovascular control centers in the brain stem and modulate sympathetic and parasympathetic neural outflow, resulting in the increased BP and HR observed during exercise. Another specific consequence of the central neural integration of these inputs during exercise is increased sympathetic neural outflow directed to the kidneys, causing renal vasoconstriction, a key reflex mechanism involved in blood flow redistribution during increased skeletal muscle work. Studies in humans have shown that muscle mechanoreflex activation inhibits cardiac vagal outflow, decreasing the sensitivity of baroreflex control of HR. Metabolite sensitization of muscle mechanoreceptors can lead to reduced sensitivity of baroreflex control of HR, with thromboxane being one of the metabolites involved, via greater inhibition of cardiac vagal outflow without affecting baroreflex control of BP or baroreflex resetting. Muscle mechanoreflex activation appears to play a predominant role in causing renal vasoconstriction, both in isolation and in the presence of local metabolites. Limited investigations in older adults and patients with cardiovascular-related disease have provided some insight into how the influence of muscle mechanoreflex activation on baroreflex function and renal vasoconstriction is altered in these populations. However, future research is warranted to better elucidate the specific effect of muscle mechanoreflex activation on baroreflex and neurovascular responses with aging and cardiovascular-related disease. Copyright © 2017 the American Physiological Society.

  5. Effects of tetracaine on voltage-activated calcium sparks in frog intact skeletal muscle fibers.

    Science.gov (United States)

    Hollingworth, Stephen; Chandler, W Knox; Baylor, Stephen M

    2006-03-01

    The properties of Ca(2+) sparks in frog intact skeletal muscle fibers depolarized with 13 mM [K(+)] Ringer's are well described by a computational model with a Ca(2+) source flux of amplitude 2.5 pA (units of current) and duration 4.6 ms (18 degrees C; Model 2 of Baylor et al., 2002). This result, in combination with the values of single-channel Ca(2+) current reported for ryanodine receptors (RyRs) in bilayers under physiological ion conditions, 0.5 pA (Kettlun et al., 2003) to 2 pA (Tinker et al., 1993), suggests that 1-5 RyR Ca(2+) release channels open during a voltage-activated Ca(2+) spark in an intact fiber. To distinguish between one and greater than one channel per spark, sparks were measured in 8 mM [K(+)] Ringer's in the absence and presence of tetracaine, an inhibitor of RyR channel openings in bilayers. The most prominent effect of 75-100 microM tetracaine was an approximately sixfold reduction in spark frequency. The remaining sparks showed significant reductions in the mean values of peak amplitude, decay time constant, full duration at half maximum (FDHM), full width at half maximum (FWHM), and mass, but not in the mean value of rise time. Spark properties in tetracaine were simulated with an updated spark model that differed in minor ways from our previous model. The simulations show that (a) the properties of sparks in tetracaine are those expected if tetracaine reduces the number of active RyR Ca(2+) channels per spark, and (b) the single-channel Ca(2+) current of an RyR channel is normal voltage-activated sparks (i.e., in the absence of tetracaine) are produced by two or more active RyR Ca(2+) channels. The question of how the activation of multiple RyRs is coordinated is discussed.

  6. AMP-activated protein kinase in contraction regulation of skeletal muscle metabolism: necessary and/or sufficient?

    DEFF Research Database (Denmark)

    Jensen, Thomas Elbenhardt; Wojtaszewski, Jørgen; Richter, Erik

    2009-01-01

    In skeletal muscle, the contraction-activated heterotrimeric 5'-AMP-activated protein kinase (AMPK) protein is proposed to regulate the balance between anabolic and catabolic processes by increasing substrate uptake and turnover in addition to regulating the transcription of proteins involved...... in mitochondrial biogenesis and other aspects of promoting an oxidative muscle phenotype. Here, the current knowledge on the expression of AMPK subunits in human quadriceps muscle and evidence from rodent studies suggesting distinct AMPK subunit expression pattern in different muscle types is reviewed. Then......, the intensity and time dependence of AMPK activation in human quadriceps and rodent muscle are evaluated. Subsequently, a major part of this review critically examines the evidence supporting a necessary and/or sufficient role of AMPK in a broad spectrum of skeletal muscle contraction-relevant processes...

  7. Abnormalities of AMPK activation and glucose uptake in cultured skeletal muscle cells from individuals with chronic fatigue syndrome.

    Directory of Open Access Journals (Sweden)

    Audrey E Brown

    Full Text Available Post exertional muscle fatigue is a key feature in Chronic Fatigue Syndrome (CFS. Abnormalities of skeletal muscle function have been identified in some but not all patients with CFS. To try to limit potential confounders that might contribute to this clinical heterogeneity, we developed a novel in vitro system that allows comparison of AMP kinase (AMPK activation and metabolic responses to exercise in cultured skeletal muscle cells from CFS patients and control subjects.Skeletal muscle cell cultures were established from 10 subjects with CFS and 7 age-matched controls, subjected to electrical pulse stimulation (EPS for up to 24h and examined for changes associated with exercise.In the basal state, CFS cultures showed increased myogenin expression but decreased IL6 secretion during differentiation compared with control cultures. Control cultures subjected to 16 h EPS showed a significant increase in both AMPK phosphorylation and glucose uptake compared with unstimulated cells. In contrast, CFS cultures showed no increase in AMPK phosphorylation or glucose uptake after 16 h EPS. However, glucose uptake remained responsive to insulin in the CFS cells pointing to an exercise-related defect. IL6 secretion in response to EPS was significantly reduced in CFS compared with control cultures at all time points measured.EPS is an effective model for eliciting muscle contraction and the metabolic changes associated with exercise in cultured skeletal muscle cells. We found four main differences in cultured skeletal muscle cells from subjects with CFS; increased myogenin expression in the basal state, impaired activation of AMPK, impaired stimulation of glucose uptake and diminished release of IL6. The retention of these differences in cultured muscle cells from CFS subjects points to a genetic/epigenetic mechanism, and provides a system to identify novel therapeutic targets.

  8. Physical Activity-Related Injury Profile in Children and Adolescents According to Their Age, Maturation, and Level of Sports Participation.

    Science.gov (United States)

    Costa E Silva, Lara; Fragoso, Maria Isabel; Teles, Júlia

    Physical activity (PA) is beneficial, enhancing healthy development. However, one-third of school-age children practicing sports regularly suffer from an injury. These injuries are associated with sex, chronological age, and PA level. To identify the importance of age, PA level, and maturity as predictors of injury in Portuguese youth. Descriptive epidemiological study. Level 3. Information about injury and PA level was assessed via 2 questionnaires (LESADO RAPIL II) from 647 subjects aged 10 to 17 years. Maturity offset according to Mirwald (time before or after peak height velocity) and Tanner-Whitehouse III bone age estimates were used to evaluate maturation. Binary logistic regression and gamma regression were used to determine significant predictors of injury and injury rate. Injury occurrence was higher for both sexes in recreational, school, and federated athletes (athletes engaged in sports that are regulated by their respective federations, with formal competition). These injuries also increased with age in boys and in the higher maturity offset group in girls. Injury rate was higher for both sexes in the no sports participation group. Early-maturing girls, with higher bone age and lower maturity offset, showed higher injury rate. Injuries in Portuguese youth were related to PA level, age, and biological maturation. Recreational, school, and federated athletes had more injury ocurrences while subjects with no sports participation had higher injury risk. Older subjects had more injuries. Early-maturing girls that had just passed peak height velocity may be particularly vulnerable to risk of sports injury because of the growing process. Increased knowledge about injury with specific PA exposure data is important to an overall risk management strategy. This study has deepened the association between injury and biological maturation variables.

  9. Antifungal and antioxidant activities of mature leaves of Myrcia splendens (Sw. DC.

    Directory of Open Access Journals (Sweden)

    F. C. Pontes

    2018-05-01

    Full Text Available Abstract In recent years, natural products with antifungal and antioxidant activities are being increasingly researched for a more sustainable alternative to the chemicals currently used for the same purpose. The plant pathogenic fungus Alternaria alternata is a causative agent of diseases in citrus, leading to huge economic losses. Antioxidants are important for the production of medicines for various diseases that may be related to the presence of free radicals, such as cancer, and in the cosmetic industry as an anti-aging agent and the food industry as preservatives. This study evaluated the antifungal and antioxidant potential of extracts of mature leaves of Myrcia splendens, a tree species that occurs in the Brazilian Cerrado. The antioxidant potential was analyzed by an assay of 1,1-diphenyl-2-picrylhydrazyl radical-scavenging method, and the antifungal activity was assessed through the evaluation of mycelial growth. Majority of the extracts exhibited a strong antioxidant activity, especially the acetonic extract (4A. The antioxidant activity may be related to the presence of phenolic compounds. However, the extracts showed no inhibitory activity of mycelial growth of the fungus tested, with the exception of dichloromethanic extract (2B, which had an inhibitory effect (10.2% at the end of testing.

  10. Maturation of Cerebellar Purkinje Cell Population Activity during Postnatal Refinement of Climbing Fiber Network

    Directory of Open Access Journals (Sweden)

    Jean-Marc Good

    2017-11-01

    Full Text Available Neural circuits undergo massive refinements during postnatal development. In the developing cerebellum, the climbing fiber (CF to Purkinje cell (PC network is drastically reshaped by eliminating early-formed redundant CF to PC synapses. To investigate the impact of CF network refinement on PC population activity during postnatal development, we monitored spontaneous CF responses in neighboring PCs and the activity of populations of nearby CF terminals using in vivo two-photon calcium imaging. Population activity is highly synchronized in newborn mice, and the degree of synchrony gradually declines during the first postnatal week in PCs and, to a lesser extent, in CF terminals. Knockout mice lacking P/Q-type voltage-gated calcium channel or glutamate receptor δ2, in which CF network refinement is severely impaired, exhibit an abnormally high level of synchrony in PC population activity. These results suggest that CF network refinement is a structural basis for developmental desynchronization and maturation of PC population activity.

  11. Endothelial Fcγ Receptor IIB Activation Blunts Insulin Delivery to Skeletal Muscle to Cause Insulin Resistance in Mice

    Science.gov (United States)

    Tanigaki, Keiji; Chambliss, Ken L.; Yuhanna, Ivan S.; Sacharidou, Anastasia; Ahmed, Mohamed; Atochin, Dmitriy N.; Huang, Paul L.

    2016-01-01

    Modest elevations in C-reactive protein (CRP) are associated with type 2 diabetes. We previously revealed in mice that increased CRP causes insulin resistance and mice globally deficient in the CRP receptor Fcγ receptor IIB (FcγRIIB) were protected from the disorder. FcγRIIB is expressed in numerous cell types including endothelium and B lymphocytes. Here we investigated how endothelial FcγRIIB influences glucose homeostasis, using mice with elevated CRP expressing or lacking endothelial FcγRIIB. Whereas increased CRP caused insulin resistance in mice expressing endothelial FcγRIIB, mice deficient in the endothelial receptor were protected. The insulin resistance with endothelial FcγRIIB activation was due to impaired skeletal muscle glucose uptake caused by attenuated insulin delivery, and it was associated with blunted endothelial nitric oxide synthase (eNOS) activation in skeletal muscle. In culture, CRP suppressed endothelial cell insulin transcytosis via FcγRIIB activation and eNOS antagonism. Furthermore, in knock-in mice harboring constitutively active eNOS, elevated CRP did not invoke insulin resistance. Collectively these findings reveal that by inhibiting eNOS, endothelial FcγRIIB activation by CRP blunts insulin delivery to skeletal muscle to cause insulin resistance. Thus, a series of mechanisms in endothelium that impairs insulin movement has been identified that may contribute to type 2 diabetes pathogenesis. PMID:27207525

  12. Activation of AMPK improves inflammation and insulin resistance in adipose tissue and skeletal muscle from pregnant women.

    Science.gov (United States)

    Liong, Stella; Lappas, Martha

    2015-12-01

    Gestational diabetes mellitus (GDM) is characterised by maternal peripheral insulin resistance and inflammation. Sterile inflammation and bacterial infection are key mediators of this enhanced inflammatory response. Adenosine monophosphate (AMP)-activated kinase (AMPK), which is decreased in insulin resistant states, possesses potent pro-inflammatory actions. There are, however, no studies on the role of AMPK in pregnancies complicated by GDM. Thus, the aims of this study were (i) to compare the expression of AMPK in adipose tissue and skeletal muscle from women with GDM and normal glucose-tolerant (NGT) pregnant women; and (ii) to investigate the effect of AMPK activation on inflammation and insulin resistance induced by the bacterial endotoxin lipopolysaccharide (LPS) and the pro-inflammatory cytokine IL-1β. When compared to NGT pregnant women, AMPKα activity was significantly lower in women with GDM as evidenced by a decrease in threonine phosphorylation of AMPKα. Activation of AMPK, using two pharmacologically distinct compounds, AICAR or phenformin, significantly suppressed LPS- or IL-1β-induced gene expression and secretion of pro-inflammatory cytokine IL-6, the chemokines IL-8 and MCP-1, and COX-2 and subsequent prostaglandin release from adipose tissue and skeletal muscle. In addition, activators of AMPK decreased skeletal muscle insulin resistance induced by LPS or IL-1β as evidenced by increased insulin-stimulated phosphorylation of IRS-1, GLUT-4 expression and glucose uptake. These findings suggest that AMPK may play an important role in inflammation and insulin resistance.

  13. Effect of high-intensity intermittent swimming training on fatty acid oxidation enzyme activity in rat skeletal muscle.

    Science.gov (United States)

    Terada, Shin; Tabata, Izumi; Higuchi, Mitsuru

    2004-02-01

    We previously reported that high-intensity exercise training significantly increased citrate synthase (CS) activity, a marker of oxidative enzyme, in rat skeletal muscle to a level equaling that attained after low-intensity prolonged exercise training (Terada et al., J Appl Physiol 90: 2019-2024, 2001). Since mitochondrial oxidative enzymes and fatty acid oxidation (FAO) enzymes are often increased simultaneously, we assessed the effect of high-intensity intermittent swimming training on FAO enzyme activity in rat skeletal muscle. Male Sprague-Dawley rats (3 to 4 weeks old) were assigned to a 10-day period of high-intensity intermittent exercise training (HIT), low-intensity prolonged exercise training (LIT), or sedentary control conditions. In the HIT group, the rats repeated fourteen 20 s swimming sessions with a weight equivalent to 14-16% of their body weight. Between the exercise sessions, a 10 s pause was allowed. Rats in the LIT group swam 6 h/day in two 3 h sessions separated by 45 min of rest. CS activity in the triceps muscle of rats in the HIT and LIT groups was significantly higher than that in the control rats by 36 and 39%, respectively. Furthermore, 3-beta hydroxyacyl-CoA dehydrogenase (HAD) activity, an important enzyme in the FAO pathway in skeletal muscle, was higher in the two training groups than in the control rats (HIT: 100%, LIT: 88%). No significant difference in HAD activity was observed between the two training groups. In conclusion, the present investigation demonstrated that high-intensity intermittent swimming training elevated FAO enzyme activity in rat skeletal muscle to a level similar to that attained after 6 h of low-intensity prolonged swimming exercise training.

  14. Phosphatase activity in relation to key litter and soil properties in mature subtropical forests in China.

    Science.gov (United States)

    Hou, Enqing; Chen, Chengrong; Wen, Dazhi; Liu, Xian

    2015-05-15

    Phosphatase-mediated phosphorus (P) mineralization is one of the critical processes in biogeochemical cycling of P and determines soil P availability in forest ecosystems; however, the regulation of soil phosphatase activity remains elusive. This study investigated the potential extracellular activities of acid phosphomonoesterase (AcPME) and phosphodiesterase (PDE) and how they were related to key edaphic properties in the L horizon (undecomposed litter) and F/H horizon (fermented and humified litter) and the underlying mineral soil at the 0-15cm depth in eight mature subtropical forests in China. AcPME activity decreased significantly in the order of F/H horizon>L horizon>mineral soil horizon, while the order for PDE activity was L horizon=F/H horizon>mineral soil horizon. AcPME (X axis) and PDE (Y axis) activities were positively correlated in all horizons with significantly higher slope in the L and F/H horizons than in the mineral soil horizon. Both AcPME and PDE activities were positively related to microbial biomass C, moisture content and water-holding capacity in the L horizon, and were positively related to soil C:P, N:P and C:N ratios and fine root (diameter≤2mm) biomass in the mineral soil horizon. Both enzyme activities were also interactively affected by forest and horizon, partly due to the interactive effect of forest and horizon on microbial biomass. Our results suggest that modulator(s) of the potential extracellular activity of phosphatases vary with horizon, depending on the relative C, P and water availability of the horizon. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Determination of the chromium content of laboratory rabbit skeletal muscles by neutron activation analysis

    International Nuclear Information System (INIS)

    Lux, F.; Trebert Haeberlin, S.; Erhardt, W.

    1986-01-01

    The chromium content of skeletal muscle of laboratory rabbits has been determined using neutron activation analysis. The procedure for separation of 51 Cr by distillation of chromium oxychloride, described in the literature, has been improved. The arrangements necessary to minimize the chromium blank values are described. The main component of this blank is caused by the residual chromium contamination of the surface of the sample vial; typical values of this component are 0.049 ng Cr (without lyophilization) and 0.12 ng Cr (with lyophilization). The analyses of standard reference materials (SRM) yielded values of the chromium contents that are in agreement (I) with the certified value in the case of NBS Citrus Leaves, and (II) with the latest published value of 9.2+-2.5 ng/g in the case of IAEA animals muscle (H-4). NBS Orchard Leaves was found not to be an appropriate SRM for testing the method. In analyses of samples of thigh muscle of bastard rabbits chromium contents of 6.2-22.9 ng/g (fresh weight basis) were obtained. Comparison of these data with a previously found value of 1.2 ng/g, the literature value [de

  16. Barley HvPAPhy_a as transgene provides high and stable phytase activities in mature barley straw and in grains.

    Science.gov (United States)

    Holme, Inger Baeksted; Dionisio, Giuseppe; Madsen, Claus Krogh; Brinch-Pedersen, Henrik

    2017-04-01

    The phytase purple acid phosphatase (HvPAPhy_a) expressed during barley seed development was evaluated as transgene for overexpression in barley. The phytase was expressed constitutively driven by the cauliflower mosaic virus 35S-promoter, and the phytase activity was measured in the mature grains, the green leaves and in the dry mature vegetative plant parts left after harvest of the grains. The T 2 -generation of HvPAPhy_a transformed barley showed phytase activity increases up to 19-fold (29 000 phytase units (FTU) per kg in mature grains). Moreover, also in green leaves and mature dry straw, phytase activities were increased significantly by 110-fold (52 000 FTU/kg) and 57-fold (51 000 FTU/kg), respectively. The HvPAPhy_a-transformed barley plants with high phytase activities possess triple potential utilities for the improvement of phosphate bioavailability. First of all, the utilization of the mature grains as feed to increase the release of bio-available phosphate and minerals bound to the phytate of the grains; secondly, the utilization of the powdered straw either directly or phytase extracted hereof as a supplement to high phytate feed or food; and finally, the use of the stubble to be ploughed into the soil for mobilizing phytate-bound phosphate for plant growth. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  17. Benzimidazole derivative small-molecule 991 enhances AMPK activity and glucose uptake induced by AICAR or contraction in skeletal muscle.

    Science.gov (United States)

    Bultot, Laurent; Jensen, Thomas E; Lai, Yu-Chiang; Madsen, Agnete L B; Collodet, Caterina; Kviklyte, Samanta; Deak, Maria; Yavari, Arash; Foretz, Marc; Ghaffari, Sahar; Bellahcene, Mohamed; Ashrafian, Houman; Rider, Mark H; Richter, Erik A; Sakamoto, Kei

    2016-10-01

    AMP-activated protein kinase (AMPK) plays diverse roles and coordinates complex metabolic pathways for maintenance of energy homeostasis. This could be explained by the fact that AMPK exists as multiple heterotrimer complexes comprising a catalytic α-subunit (α1 and α2) and regulatory β (β1 and β2)- and γ (γ1, γ2, γ3)-subunits, which are uniquely distributed across different cell types. There has been keen interest in developing specific and isoform-selective AMPK-activating drugs for therapeutic use and also as research tools. Moreover, establishing ways of enhancing cellular AMPK activity would be beneficial for both purposes. Here, we investigated if a recently described potent AMPK activator called 991, in combination with the commonly used activator 5-aminoimidazole-4-carboxamide riboside or contraction, further enhances AMPK activity and glucose transport in mouse skeletal muscle ex vivo. Given that the γ3-subunit is exclusively expressed in skeletal muscle and has been implicated in contraction-induced glucose transport, we measured the activity of AMPKγ3 as well as ubiquitously expressed γ1-containing complexes. We initially validated the specificity of the antibodies for the assessment of isoform-specific AMPK activity using AMPK-deficient mouse models. We observed that a low dose of 991 (5 μM) stimulated a modest or negligible activity of both γ1- and γ3-containing AMPK complexes. Strikingly, dual treatment with 991 and 5-aminoimidazole-4-carboxamide riboside or 991 and contraction profoundly enhanced AMPKγ1/γ3 complex activation and glucose transport compared with any of the single treatments. The study demonstrates the utility of a dual activator approach to achieve a greater activation of AMPK and downstream physiological responses in various cell types, including skeletal muscle. Copyright © 2016 the American Physiological Society.

  18. Lipoprotein particle distribution and skeletal muscle lipoprotein lipase activity after acute exercise.

    Science.gov (United States)

    Harrison, Michael; Moyna, Niall M; Zderic, Theodore W; O'Gorman, Donal J; McCaffrey, Noel; Carson, Brian P; Hamilton, Marc T

    2012-07-10

    Many of the metabolic effects of exercise are due to the most recent exercise session. With recent advances in nuclear magnetic resonance spectroscopy (NMRS), it is possible to gain insight about which lipoprotein particles are responsible for mediating exercise effects. Using a randomized cross-over design, very low density lipoprotein (VLDL) responses were evaluated in eight men on the morning after i) an inactive control trial (CON), ii) exercising vigorously on the prior evening for 100 min followed by fasting overnight to maintain an energy and carbohydrate deficit (EX-DEF), and iii) after the same exercise session followed by carbohydrate intake to restore muscle glycogen and carbohydrate balance (EX-BAL). The intermediate, low and high density lipoprotein particle concentrations did not differ between trials. Fasting triglyceride (TG) determined biochemically, and mean VLDL size were lower in EX-DEF but not in EX-BAL compared to CON, primarily due to a reduction in VLDL-TG in the 70-120 nm (large) particle range. In contrast, VLDL-TG was lower in both EX-DEF and EX-BAL compared to CON in the 43-55 nm (medium) particle range. VLDL-TG in smaller particles (29-43 nm) was unaffected by exercise. Because the majority of VLDL particles were in this smallest size range and resistant to change, total VLDL particle concentration was not different between any of these conditions. Skeletal muscle lipoprotein lipase (LPL) activity was also not different across these 3 trials. However, in CON only, the inter-individual differences in LPL activity were inversely correlated with fasting TG, VLDL-TG, total, large and small VLDL particle concentration and VLDL size, indicating a regulatory role for LPL in the non-exercised state. These findings reveal a high level of differential regulation between different sized triglyceride-rich lipoproteins following exercise and feeding, in the absence of changes in LPL activity.

  19. Activation of estrogen response elements is mediated both via estrogen and muscle contractions in rat skeletal muscle myotubes

    DEFF Research Database (Denmark)

    Wiik, A.; Hellsten, Ylva; Berthelson, P.

    2009-01-01

    is ER independent. The muscle contraction-induced transactivation of ERE and increase in ERbeta mRNA were instead found to be MAP kinase (MAPK) dependent. This study demonstrates for the first time that muscle contractions have a similar functional effect as estrogen in skeletal muscle myotubes, causing......The aim of the present study was to investigate the activation of estrogen response elements (EREs) by estrogen and muscle contractions in rat myotubes in culture and to assess whether the activation is dependent on the estrogen receptors (ERs). In addition, the effect of estrogen and contraction...... on the mRNA levels of ERalpha and ERbeta was studied to determine the functional consequence of the transactivation. Myoblasts were isolated from rat skeletal muscle and transfected with a vector consisting of sequences of EREs coupled to the gene for luciferase. The transfected myoblasts were...

  20. 5'AMP activated protein kinase expression in human skeletal muscle: effects of strength training and type 2 diabetes

    DEFF Research Database (Denmark)

    Wojtaszewski, Jørgen; Birk, Jesper Bratz; Frøsig, Christian

    2005-01-01

    adaptations within the AMPK system itself. We investigated the effect of strength training and T2DM on the isoform expression and the heterotrimeric composition of the AMPK in human skeletal muscle. Ten patients with T2DM and seven healthy subjects strength trained (T) one leg for 6 weeks, while the other leg......Strength training enhances insulin sensitivity and represents an alternative to endurance training for patients with type 2 diabetes (T2DM). The 5'AMP-activated protein kinase (AMPK) may mediate adaptations in skeletal muscle in response to exercise training; however, little is known about...... remained untrained (UT). Muscle biopsies were obtained before and after the training period. Basal AMPK activity and protein/mRNA expression of both catalytic (alpha1 and alpha2) and regulatory (beta1, beta2, gamma1, gamma2a, gamma2b and gamma3) AMPK isoforms were independent of T2DM, whereas the protein...

  1. Phospholemman is not required for the acute stimulation of Na+-K+-ATPase α2-activity during skeletal muscle fatigue

    Science.gov (United States)

    Manoharan, Palanikumar; Radzyukevich, Tatiana L.; Hakim Javadi, Hesamedin; Stiner, Cory A.; Landero Figueroa, Julio A.; Lingrel, Jerry B

    2015-01-01

    The Na+-K+-ATPase α2-isoform in skeletal muscle is rapidly stimulated during muscle use and plays a critical role in fatigue resistance. The acute mechanisms that stimulate α2-activity are not completely known. This study examines whether phosphorylation of phospholemman (PLM/FXYD1), a regulatory subunit of Na+-K+-ATPase, plays a role in the acute stimulation of α2 in working muscles. Mice lacking PLM (PLM KO) have a normal content of the α2-subunit and show normal exercise capacity, in contrast to the greatly reduced exercise capacity of mice that lack α2 in the skeletal muscles. Nerve-evoked contractions in vivo did not induce a change in total PLM or PLM phosphorylated at Ser63 or Ser68, in either WT or PLM KO. Isolated muscles of PLM KO mice maintain contraction and resist fatigue as well as wild type (WT). Rb+ transport by the α2-Na+-K+-ATPase is stimulated to the same extent in contracting WT and contracting PLM KO muscles. Phosphorylation of sarcolemmal membranes prepared from WT but not PLM KO skeletal muscles stimulates the activity of both α1 and α2 in a PLM-dependent manner. The stimulation occurs by an increase in Na+ affinity without significant change in Vmax and is more effective for α1 than α2. These results demonstrate that phosphorylation of PLM is capable of stimulating the activity of both isozymes in skeletal muscle; however, contractile activity alone is not sufficient to induce PLM phosphorylation. Importantly, acute stimulation of α2, sufficient to support exercise and oppose fatigue, does not require PLM or its phosphorylation. PMID:26468207

  2. Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase

    DEFF Research Database (Denmark)

    Matthews, V B; Åström, Maj-Brit; Chan, M H S

    2009-01-01

    C12 skeletal muscle cells were electrically stimulated to mimic contraction. L6 myotubes and isolated rat extensor digitorum longus muscles were treated with BDNF and phosphorylation of the proteins AMP-activated protein kinase (AMPK) (Thr(172)) and acetyl coenzyme A carboxylase beta (ACCbeta) (Ser...... kinase (p44/42 Thr(202)/Tyr(204)) phosphorylation in these muscles. In addition, phosphorylation of ACCbeta was markedly elevated in the Bdnf electroporated muscles. CONCLUSIONS/INTERPRETATION: These data identify BDNF as a contraction-inducible protein in skeletal muscle that is capable of enhancing...

  3. Comparative Studies on Bioactive Constituents in Hawk Tea Infusions with Different Maturity Degree and Their Antioxidant Activities

    Directory of Open Access Journals (Sweden)

    Ming Yuan

    2014-01-01

    Full Text Available Hawk tea (Litsea coreana var. lanuginose is a very popular herbal tea in the southwest of China. According to the maturity degree of raw materials, Hawk tea can usually be divided into three types: Hawk bud tea (HB, Hawk primary leaf tea (HP, and Hawk mature leaf tea (HM. In this study, some of the bioactive constituents and antioxidant properties of the three kinds of Hawk tea infusions were comparatively investigated. The results showed that the contents of total flavonoids, vitamin C, and carbohydrates in Hawk bud tea infusion (HBI were higher than those in Hawk primary leaf tea infusion (HPI and Hawk mature leaf tea infusion (HMI. HPI had higher contents of total polyphenols and exhibited better DPPH radical scavenging activity and ferric reducing activity power. HBI could provide more effective protection against erythrocyte hemolysis. As age is going from bud to mature leaf, the ability to inhibit the formation of low density lipoprotein (LDL conjugated diene and the loss of tryptophan fluorescence decreased. The bioactive constituents and antioxidant activities of Hawk tea infusions were significantly affected by the maturity degree of the raw material.

  4. Roles of sedentary aging and lifelong physical activity on exchange of glutathione across exercising human skeletal muscle

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Mortensen, Stefan Peter; Cabo, Helena

    2014-01-01

    Reactive oxygen species (ROS) are important signaling molecules with regulatory functions, and in young and adult organisms, the formation of ROS is increased during skeletal muscle contractions. However, ROS can be deleterious to cells when not sufficiently counterbalanced by the antioxidant sys...... underlying skeletal muscle and vascular dysfunction with sedentary aging. Lifelong physical activity up-regulates antioxidant systems which may be one of the mechanisms underlying the lack of exercise-induced increase in GSSG....... system. Aging is associated with accumulation of oxidative damage to lipids, DNA and proteins. Given the pro-oxidant effect of skeletal muscle contractions, this effect of age could be a result of excessive ROS formation. We evaluated the effect of acute exercise on changes in blood redox state across...... the leg of young (23±1 years) and older (66±2 years) sedentary humans by measuring the whole blood concentration of the reduced (GSH) and oxidized (GSSG) form of the antioxidant glutathione. To assess the role of physical activity, lifelong physically active older subjects (62±2 years) were included...

  5. Actively station: Effects on global cognition of mature adults and healthy elderly program using eletronic games

    Directory of Open Access Journals (Sweden)

    Tiago Nascimento Ordonez

    Full Text Available ABSTRACT Studies show that aging is accompanied by decline in cognitive functions but also indicate that interventions, such as training on electronic games, can enhance performance and promote maintenance of cognitive abilities in healthy older adults. Objective: To investigate the effects of an electronic game program, called Actively Station, on the performance of global cognition of adults aged over 50 years. Methods: 124 mature and elderly adults enrolled in the "Actively Station" cognitive stimulation program of São Caetano do Sul City, in the State of São Paulo, participated in training for learning of electronic games. Participants were divided into two groups: training group (TG n=102 and control group (CG n=22. Protocol: a sociodemographic questionnaire, the Mini-Mental State Examination (MMSE, the Addenbrooke's Cognitive Examination Revised (ACE-R, the Memory Complaint Questionnaire (MAC-Q, the scale of frequency of forgetfulness, the Geriatric Depression Scale (GDS-15, the Geriatric Anxiety Inventory (GAI, the Global Satisfaction with Life Scale, and two scales on learning in the training. Results: The cognitive performance of the TG improved significantly after the program, particularly in the domains of language and memory, and there was a decrease on the anxiety index and frequency of memory complaints, when compared to the CG. Conclusion: These findings suggest that the acquisition of new knowledge and the use of new stimuli, such as electronic games, can promote improvements in cognition and mood and reduce the frequency of memory complaints.

  6. p38 MAPK activation upregulates proinflammatory pathways in skeletal muscle cells from insulin-resistant type 2 diabetic patients

    DEFF Research Database (Denmark)

    Brown, Audrey E; Palsgaard, Jane; Borup, Rehannah

    2015-01-01

    Skeletal muscle is the key site of peripheral insulin resistance in type 2 diabetes. Insulin-stimulated glucose uptake is decreased in differentiated diabetic cultured myotubes, which is in keeping with a retained genetic/epigenetic defect of insulin action. We investigated differences in gene...... expression during differentiation between diabetic and control muscle cell cultures. Microarray analysis was performed using skeletal muscle cell cultures established from type 2 diabetic patients with a family history of type 2 diabetes and clinical evidence of marked insulin resistance and nondiabetic...... significantly, it did not improve insulin-stimulated glucose uptake. Increased cytokine expression driven by increased p38 MAPK activation is a key feature of cultured myotubes derived from insulin-resistant type 2 diabetic patients. p38 MAPK inhibition decreased cytokine expression but did not affect...

  7. Activation of muscarinic M-1 cholinoceptors by curcumin to increase glucose uptake into skeletal muscle isolated from Wistar rats.

    Science.gov (United States)

    Cheng, Tse-Chou; Lin, Chian-Shiung; Hsu, Chih-Chieh; Chen, Li-Jen; Cheng, Kai-Chun; Cheng, Juei-Tang

    2009-11-20

    Curcumin, an active principle contained in rhizome of Curcuma longa, has been mentioned to show merit for diabetes through its anti-oxidative and anti-inflammatory properties. In the present study, we found that curcumin caused a concentration-dependent increase of glucose uptake into skeletal muscle isolated from Wistar rats. This action was inhibited by pirenzepine at concentration enough to block muscarinic M-1 cholinoceptor (M(1)-mAChR). In radioligand binding assay, the binding of [(3)H]-pirenzepine was also displaced by curcumin in a concentration-dependent manner. In the presence of inhibitors for PLC-PI3K pathway, either U73122 (phospholipase C inhibitor) or LY294002 (phosphoinositide 3-kinase inhibitor), curcumin-stimulated glucose uptake into skeletal muscle was markedly reduced. In Western blotting analysis, the membrane protein level of glucose transporter 4 (GLUT4) increased by curcumin was also reversed by blockade of M(1)-mAChR or PLC-PI3K pathway in a same manner. In conclusion, the obtained results suggest that curcumin can activate M(1)-mAChR at concentrations lower than to scavenge free radicals for increase of glucose uptake into skeletal muscle through PLC-PI3-kinase pathway.

  8. Activated protein synthesis and suppressed protein breakdown signaling in skeletal muscle of critically ill patients

    DEFF Research Database (Denmark)

    Jespersen, Jakob G; Nedergaard, Anders; Reitelseder, Søren

    2011-01-01

    Skeletal muscle mass is controlled by myostatin and Akt-dependent signaling on mammalian target of rapamycin (mTOR), glycogen synthase kinase 3β (GSK3β) and forkhead box O (FoxO) pathways, but it is unknown how these pathways are regulated in critically ill human muscle. To describe factors invol...... involved in muscle mass regulation, we investigated the phosphorylation and expression of key factors in these protein synthesis and breakdown signaling pathways in thigh skeletal muscle of critically ill intensive care unit (ICU) patients compared with healthy controls....

  9. Activated protein synthesis and suppressed protein breakdown signaling in skeletal muscle of critically ill patients

    DEFF Research Database (Denmark)

    Jespersen, Jakob G; Nedergaard, Anders; Reitelseder, Søren

    2011-01-01

    Skeletal muscle mass is controlled by myostatin and Akt-dependent signaling on mammalian target of rapamycin (mTOR), glycogen synthase kinase 3ß (GSK3ß) and forkhead box O (FoxO) pathways, but it is unknown how these pathways are regulated in critically ill human muscle. To describe factors invol...... involved in muscle mass regulation, we investigated the phosphorylation and expression of key factors in these protein synthesis and breakdown signaling pathways in thigh skeletal muscle of critically ill intensive care unit (ICU) patients compared with healthy controls....

  10. Policosanol composition, antioxidant and anti-arthritic activities of milk thistle (Silybium marianum L.) oil at different seed maturity stages.

    Science.gov (United States)

    Harrabi, Saoussem; Ferchichi, Azza; Bacheli, Asma; Fellah, Hayet

    2018-04-16

    Several anti-arthritic drugs and synthetic antioxidants have wide pharmaceutical uses and are often associated with various side effects on the human health. Dietary seed oils and their minor components like policosanol may offer an effective alternative treatment for arthritic and oxidative-stress related diseases. The biological effects of seed oils were affected by different parameters such as the stage of seed maturity. Hence, this study seeks to determine the policosanol content, antioxidant and anti-arthritic activities of milk thistle (Silybium marianum L.) oil extracted at various stages of seed maturation. Milk thistle oil samples were extracted from seeds collected at three maturation stages (immature, intermediate, and mature). The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethyl-benzthiazoline-6-sulfonic acid) (ABTS) radical scavenging assays were used to determine the antioxidant activity of the extracted oils. The anti-arthritic activity of oil samples was evaluated with bovine serum protein denaturation and egg albumin denaturation methods. Gas chromatography coupled to mass spectrometry (GC-MS) was employed to determine the policosanol profile. Policosanol profile, antioxidant and anti-arthritic activities of milk thistle oil were influenced by the seed maturity stages. The oil extracted from the immature seeds had the highest total policosanol content (987.68 mg/kg of oil) and displayed the maximum antiradical activity (96.42% and 90.35% for DPPH test and ABTS assay, respectively). Nine aliphatic alcohols were identified in the milk thistle oil. The dominant poliosanol in the mature seed oil was octacosanol (75.44%), while triacontanol was the major compound (40.25%) in the immature seed oil. Additionally, the maximum inhibition of bovine serum protein denaturation (92.53%) and egg albumin denaturation (86.36%) were observed in immature seed oil as compared to mature seed oil. A high correlation was found between the total

  11. Is Greulich–Pyle age estimation applicable for determining maturation in male Africans?

    OpenAIRE

    Alan G. Morri; Kundisai A. Dembetembe

    2012-01-01

    Skeletal age estimation as a means of assessing development and skeletal maturation in children and adolescents is of great importance for clinical and forensic purposes. The skeletal age of a test population is estimated by comparison with established standards, the most common standards being those in the Radiographic atlas of skeletal development of the hand and wristpublished by Greulich and Pyle in 1959. These standards are based on the assumption that skeletal maturity in male individua...

  12. Structure of the Mature Streptococcal Cysteine Protease Exotoxin mSpeB in Its Active Dimeric Form

    DEFF Research Database (Denmark)

    Olsen, Johan G; Dagil, Robert; Niclasen, Louise Meinert

    2009-01-01

    Invasive infections of Streptococcus pyogenes are dependent on the cysteine protease streptococcal pyrogenic exotoxin B. Previous structures of the enzyme have not disclosed the proper active-site configuration. Here, the crystal structure of the mature enzyme is presented to 1.55 A, disclosing...

  13. Lipoprotein particle distribution and skeletal muscle lipoprotein lipase activity after acute exercise

    LENUS (Irish Health Repository)

    Harrison, Michael

    2012-06-06

    AbstractBackgroundMany of the metabolic effects of exercise are due to the most recent exercise session. With recent advances in nuclear magnetic resonance spectroscopy (NMRS), it is possible to gain insight about which lipoprotein particles are responsible for mediating exercise effects.MethodsUsing a randomized cross-over design, very low density lipoprotein (VLDL) responses were evaluated in eight men on the morning after i) an inactive control trial (CON), ii) exercising vigorously on the prior evening for 100 min followed by fasting overnight to maintain an energy and carbohydrate deficit (EX-DEF), and iii) after the same exercise session followed by carbohydrate intake to restore muscle glycogen and carbohydrate balance (EX-BAL).ResultsThe intermediate, low and high density lipoprotein particle concentrations did not differ between trials. Fasting triglyceride (TG) determined biochemically, and mean VLDL size were lower in EX-DEF but not in EX-BAL compared to CON, primarily due to a reduction in VLDL-TG in the 70–120 nm (large) particle range. In contrast, VLDL-TG was lower in both EX-DEF and EX-BAL compared to CON in the 43–55 nm (medium) particle range. VLDL-TG in smaller particles (29–43 nm) was unaffected by exercise. Because the majority of VLDL particles were in this smallest size range and resistant to change, total VLDL particle concentration was not different between any of these conditions. Skeletal muscle lipoprotein lipase (LPL) activity was also not different across these 3 trials. However, in CON only, the inter-individual differences in LPL activity were inversely correlated with fasting TG, VLDL-TG, total, large and small VLDL particle concentration and VLDL size, indicating a regulatory role for LPL in the non-exercised state.ConclusionsThese findings reveal a high level of differential regulation between different sized triglyceride-rich lipoproteins following exercise and feeding, in the absence of changes in LPL activity.

  14. Lipoprotein particle distribution and skeletal muscle lipoprotein lipase activity after acute exercise

    Directory of Open Access Journals (Sweden)

    Harrison Michael

    2012-07-01

    Full Text Available Abstract Background Many of the metabolic effects of exercise are due to the most recent exercise session. With recent advances in nuclear magnetic resonance spectroscopy (NMRS, it is possible to gain insight about which lipoprotein particles are responsible for mediating exercise effects. Methods Using a randomized cross-over design, very low density lipoprotein (VLDL responses were evaluated in eight men on the morning after i an inactive control trial (CON, ii exercising vigorously on the prior evening for 100 min followed by fasting overnight to maintain an energy and carbohydrate deficit (EX-DEF, and iii after the same exercise session followed by carbohydrate intake to restore muscle glycogen and carbohydrate balance (EX-BAL. Results The intermediate, low and high density lipoprotein particle concentrations did not differ between trials. Fasting triglyceride (TG determined biochemically, and mean VLDL size were lower in EX-DEF but not in EX-BAL compared to CON, primarily due to a reduction in VLDL-TG in the 70–120 nm (large particle range. In contrast, VLDL-TG was lower in both EX-DEF and EX-BAL compared to CON in the 43–55 nm (medium particle range. VLDL-TG in smaller particles (29–43 nm was unaffected by exercise. Because the majority of VLDL particles were in this smallest size range and resistant to change, total VLDL particle concentration was not different between any of these conditions. Skeletal muscle lipoprotein lipase (LPL activity was also not different across these 3 trials. However, in CON only, the inter-individual differences in LPL activity were inversely correlated with fasting TG, VLDL-TG, total, large and small VLDL particle concentration and VLDL size, indicating a regulatory role for LPL in the non-exercised state. Conclusions These findings reveal a high level of differential regulation between different sized triglyceride-rich lipoproteins following exercise and feeding, in the absence of changes in

  15. The influence of acute resistance exercise on cyclooxygenase-1 and -2 activity and protein levels in human skeletal muscle.

    Science.gov (United States)

    Carroll, Chad C; O'Connor, Devin T; Steinmeyer, Robert; Del Mundo, Jonathon D; McMullan, David R; Whitt, Jamie A; Ramos, Jahir E; Gonzales, Rayna J

    2013-07-01

    This study evaluated the activity and content of cyclooxygenase (COX)-1 and -2 in response to acute resistance exercise (RE) in human skeletal muscle. Previous work suggests that COX-1, but not COX-2, is the primary COX isoform elevated with resistance exercise in human skeletal muscle. COX activity, however, has not been assessed after resistance exercise in humans. It was hypothesized that RE would increase COX-1 but not COX-2 activity. Muscle biopsies were taken from the vastus lateralis of nine young men (25 ± 1 yr) at baseline (preexercise), 4, and 24 h after a single bout of knee extensor RE (three sets of 10 repetitions at 70% of maximum). Tissue lysate was assayed for COX-1 and COX-2 activity. COX-1 and COX-2 protein levels were measured via Western blot analysis. COX-1 activity increased at 4 h (P 0.05) with acute RE. In contrast, COX-2 protein levels were nearly 3-fold greater (P > 0.05) at 4 h and 5-fold greater (P = 0.06) at 24 h, compared with preexercise. In conclusion, COX-1 activity increases transiently with exercise independent of COX-1 protein levels. In contrast, both COX-2 activity and protein levels were elevated with exercise, and this elevation persisted to at least 24 h after RE.

  16. Assessment of satellite cell number and activity status in human skeletal muscle biopsies

    DEFF Research Database (Denmark)

    Mackey, Abigail; Kjaer, Michael; Charifi, Nadia

    2009-01-01

    The primary aim of our study was to validate the assessment of myonuclear and satellite cell number in biopsies from human skeletal muscle. We found that 25 type I and 25 type II fibers are sufficient to estimate the mean number of myonuclei per fiber. In contrast, the assessment of satellite cells...

  17. New formula to objectively evaluate skeletal maturation using lateral cephalometric radiographs Nova fórmula para avaliação objetiva da maturação esquelética em radiografias cefalométricas laterais

    Directory of Open Access Journals (Sweden)

    Maria de Paula Caldas

    2007-12-01

    Full Text Available The aim of this study was to establish two new formulas for objectively evaluating skeletal maturation of cervical vertebrae in female and male Brazilian subjects using lateral cephalometric radiographs. The sample included 128 girls and 110 boys, aged 7.0 to 15.9 years, from the files of the Oral Radiology Clinic, Piracicaba Dental School, University of Campinas (Unicamp, SP, Brazil. The cervical vertebral bodies of C3 and C4 were traced and measured and regression formulas were developed in order to determine cervical vertebral bone age. Another sample of lateral teleradiographs and hand-wrist radiographs of 55 girls and 54 boys (aged 7.0 to 15.9 years was used to verify the reliability of the developed regression formulas, as compared with bone age assessed using the Tanner et al.15 (2001 Method (TW3 in hand-wrist radiographs. The analysis of both the boys’ and girls’ data (ANOVA showed no statistical difference between cervical vertebral bone age, bone age, and chronological age, indicating that these formulas can be used in this population (p = 0.5721 and p = 0.6007 for girls and boys, respectively. Female cervical vertebral bodies of C3 and C4 increased in an accelerated manner from 10 to 13 years. Analysis of the male sample showed that C3 measurements increased in an accelerated manner from 12 to 15 years. The C4 measurements, however, did not increase at all. Using cervical vertebral bone age it is possible to evaluate skeletal maturation objectively in cephalometric radiographs.O objetivo deste estudo foi estabelecer dois novos métodos para meninas e meninos brasileiros, no intuito de determinar de forma objetiva a maturação esquelética das vértebras cervicais em radiografias cefalométricas laterais. Foram selecionados 128 meninas e 110 meninos, com faixa etária variando entre 7 e 15,9 anos, pertencentes à Clínica de Radiologia da Faculdade de Odontologia de Piracicaba da Universidade de Campinas (Unicamp. Os corpos da

  18. Maturity associated variance in physical activity and health-related quality of life in adolescent females: a mediated effects model.

    Science.gov (United States)

    Smart, Joan E Hunter; Cumming, Sean P; Sherar, Lauren B; Standage, Martyn; Neville, Helen; Malina, Robert M

    2012-01-01

    This study tested a mediated effects model of psychological and behavioral adaptation to puberty within the context of physical activity (PA). Biological maturity status, physical self-concept, PA, and health-related quality of life (HRQoL) were assessed in 222 female British year 7 to 9 pupils (mean age = 12.7 years, SD = .8). Structural equation modeling using maximum likelihood estimation and bootstrapping procedures supported the hypothesized model. Maturation status was inversely related to perceptions of sport competence, body attractiveness, and physical condition; and indirectly and inversely related to physical self-worth, PA, and HRQoL. Examination of the bootstrap-generated bias-corrected confidence intervals representing the direct and indirect paths between suggested that physical self-concept partially mediated the relations between maturity status and PA, and maturity status and HRQoL. Evidence supports the contention that perceptions of the physical self partially mediate relations maturity, PA, and HRQoL in adolescent females.

  19. Suboptimal inhibition of protease activity in human immunodeficiency virus type 1: Effects on virion morphogenesis and RNA maturation

    International Nuclear Information System (INIS)

    Moore, Michael D.; Fu, William; Soheilian, Ferri; Nagashima, Kunio; Ptak, Roger G.; Pathak, Vinay K.; Hu, Wei-Shau

    2008-01-01

    Protease activity within nascently released human immunodeficiency virus type 1 (HIV-1) particles is responsible for the cleavage of the viral polyproteins Gag and Gag-Pol into their constituent parts, which results in the subsequent condensation of the mature conical core surrounding the viral genomic RNA. Concomitant with viral maturation is a conformational change in the packaged viral RNA from a loosely associated dimer into a more thermodynamically stable form. In this study we used suboptimal concentrations of two protease inhibitors, lopinavir and atazanavir, to study their effects on Gag polyprotein processing and on the properties of the RNA in treated virions. Analysis of the treated virions demonstrated that even with high levels of inhibition of viral infectivity (IC 90 ), most of the Gag and Gag-Pol polyproteins were processed, although slight but significant increases in processing intermediates of Gag were detected. Drug treatments also caused a significant increase in the proportion of viruses displaying either immature or aberrant mature morphologies. The aberrant mature particles were characterized by an electron-dense region at the viral periphery and an electron-lucent core structure in the viral center, possibly indicating exclusion of the genomic RNA from these viral cores. Intriguingly, drug treatments caused only a slight decrease in overall thermodynamic stability of the viral RNA dimer, suggesting that the dimeric viral RNA was able to mature in the absence of correct core condensation

  20. Superoxide activates a GDP-sensitive proton conductance in skeletal muscle mitochondria from king penguin (Aptenodytes patagonicus).

    Science.gov (United States)

    Talbot, Darren A; Hanuise, Nicolas; Rey, Benjamin; Rouanet, Jean-Louis; Duchamp, Claude; Brand, Martin D

    2003-12-26

    We present the partial nucleotide sequence of the avian uncoupling protein (avUCP) gene from king penguin (Aptenodytes patagonicus), showing that the protein is 88-92% identical to chicken (Gallus gallus), turkey (Meleagris gallopavo), and hummingbird (Eupetomena macroura). We show that superoxide activates the proton conductance of mitochondria isolated from king penguin skeletal muscle. GDP abolishes the superoxide-activated proton conductance, indicating that it is mediated via avUCP. In the absence of superoxide there is no GDP-sensitive component of the proton conductance from penguin muscle mitochondria demonstrating that avUCP plays no role in the basal proton leak.

  1. Protein kinase C {alpha} activity is important for contraction-induced FXYD1 phosphorylation in skeletal muscle

    DEFF Research Database (Denmark)

    Thomassen, Martin; Rose, Adam John; Jensen, Thomas Elbenhardt

    2011-01-01

    Exercise induced phosphorylation of FXYD1 is a potential important regulator of Na(+), K(+) pump activity. It was investigated if skeletal muscle contractions induce phosphorylation of FXYD1 and if Protein Kinase C a (PKCa) activity is a prerequisite for this possible mechanism. In part 1, human...... muscle biopsies were obtained at rest, after 30 s of high intensity exercise (166±31% of VO(2max)) and after a subsequent 20 min of moderate intensity exercise (79±8% of VO(2max)). In general, FXYD1 phosphorylation was increased compared to rest both after 30 s (P...

  2. Myostatin in relation to physical activity and dysglycaemia and its effect on energy metabolism in human skeletal muscle cells.

    Science.gov (United States)

    Hjorth, M; Pourteymour, S; Görgens, S W; Langleite, T M; Lee, S; Holen, T; Gulseth, H L; Birkeland, K I; Jensen, J; Drevon, C A; Norheim, F

    2016-05-01

    Some health benefits of exercise may be explained by an altered secretion of myokines. Because previous focus has been on upregulated myokines, we screened for downregulated myokines and identified myostatin. We studied the expression of myostatin in relation to exercise and dysglycaemia in skeletal muscle, adipose tissue and plasma. We further examined some effects of myostatin on energy metabolism in primary human muscle cells and Simpson-Golabi-Behmel syndrome (SGBS) adipocytes. Sedentary men with or without dysglycaemia underwent a 45-min acute bicycle test before and after 12 weeks of combined endurance and strength training. Blood samples and biopsies from m. vastus lateralis and adipose tissue were collected. Myostatin mRNA expression was reduced in skeletal muscle after acute as well as long-term exercise and was even further downregulated by acute exercise on top of 12-week training. Furthermore, the expression of myostatin at baseline correlated negatively with insulin sensitivity. Myostatin expression in the adipose tissue increased after 12 weeks of training and correlated positively with insulin sensitivity markers. In cultured muscle cells but not in SGBS cells, myostatin promoted an insulin-independent increase in glucose uptake. Furthermore, muscle cells incubated with myostatin had an enhanced rate of glucose oxidation and lactate production. Myostatin was differentially expressed in the muscle and adipose tissue in relation to physical activity and dysglycaemia. Recombinant myostatin increased the consumption of glucose in human skeletal muscle cells, suggesting a complex regulatory role of myostatin in skeletal muscle homeostasis. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  3. Regulation of glycogen synthesis in rat skeletal muscle after glycogen-depleting contractile activity: effects of adrenaline on glycogen synthesis and activation of glycogen synthase and glycogen phosphorylase.

    OpenAIRE

    Franch, J; Aslesen, R; Jensen, J

    1999-01-01

    We investigated the effects of insulin and adrenaline on the rate of glycogen synthesis in skeletal muscles after electrical stimulation in vitro. The contractile activity decreased the glycogen concentration by 62%. After contractile activity, the glycogen stores were fully replenished at a constant and high rate for 3 h when 10 m-i.u./ml insulin was present. In the absence of insulin, only 65% of the initial glycogen stores was replenished. Adrenaline decreased insulin-stimulated glycogen s...

  4. Chemical Compositions and Macrophage Activation of Polysaccharides from Leon's Mane Culinary-Medicinal Mushroom Hericium erinaceus (Higher Basidiomycetes) in Different Maturation Stages.

    Science.gov (United States)

    Li, Qiao-Zhen; Wu, Di; Chen, Xia; Zhou, Shuai; Liu, Yanfang; Yang, Yan; Cui, Fengjie

    2015-01-01

    We studied the effect of the maturation stage on the chemical compositions and macrophage activation activity of polysaccharides from the culinary-medicinal mushroom Hericium erinaceus. Results showed that total polysaccharides increased, whereas protein content decreased with the maturation stage development of fruiting body. Nine polysaccharide fractions, 3 from each of the maturity stages IV (small fungal spine stage), V (mid-fungal spine stage) and VI (mature), were prepared using the gradient ethanol precipitation method. The polysaccharide fraction HP4A isolated from the maturating-stage (stage IV) fruiting body had a significant difference from the fractions HP5A (stage V) and HP6A (stage VI) in the molecular weight distribution and monosaccharide compositions. Immunostimulating tests revealed that the polysaccharide fraction HP6 isolated from the mature stage (stage VI) fruiting body presented higher macrophage activation activity. Our findings provided important information for the harvest and use of H. erinaceus with higher qualities and functional benefits.

  5. Matured Hop Bittering Components Induce Thermogenesis in Brown Adipose Tissue via Sympathetic Nerve Activity.

    Directory of Open Access Journals (Sweden)

    Yumie Morimoto-Kobayashi

    Full Text Available Obesity is the principal symptom of metabolic syndrome, which refers to a group of risk factors that increase the likelihood of atherosclerosis. In recent decades there has been a sharp rise in the incidence of obesity throughout the developed world. Iso-α-acids, the bitter compounds derived from hops in beer, have been shown to prevent diet-induced obesity by increasing lipid oxidation in the liver and inhibition of lipid absorption from the intestine. Whereas the sharp bitterness induced by effective dose of iso-α-acids precludes their acceptance as a nutrient, matured hop bittering components (MHB appear to be more agreeable. Therefore, we tested MHB for an effect on ameliorating diet-induced body fat accumulation in rodents. MHB ingestion had a beneficial effect but, compared to iso-α-acids and despite containing structurally similar compounds, acted via different mechanisms to reduce body fat accumulation. MHB supplementation significantly reduced body weight gain, epididymal white adipose tissue weight, and plasma non-esterified free fatty acid levels in diet-induced obese mice. We also found that uncoupling protein 1 (UCP1 expression in brown adipose tissue (BAT was significantly increased in MHB-fed mice at both the mRNA and protein levels. In addition, MHB administration in rats induced the β-adrenergic signaling cascade, which is related to cAMP accumulation in BAT, suggesting that MHB could modulate sympathetic nerve activity innervating BAT (BAT-SNA. Indeed, single oral administration of MHB elevated BAT-SNA in rats, and this elevation was dissipated by subdiaphragmatic vagotomy. Single oral administration of MHB maintained BAT temperature at a significantly higher level than in control rats. Taken together, these findings indicate that MHB ameliorates diet-induced body fat accumulation, at least partly, by enhancing thermogenesis in BAT via BAT-SNA activation. Our data suggests that MHB is a useful tool for developing functional

  6. Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans.

    Science.gov (United States)

    Petrie, Michael A; Kimball, Amy L; McHenry, Colleen L; Suneja, Manish; Yen, Chu-Ling; Sharma, Arpit; Shields, Richard K

    2016-01-01

    Skeletal muscle exercise regulates several important metabolic genes in humans. We know little about the effects of environmental stress (heat) and mechanical stress (vibration) on skeletal muscle. Passive mechanical stress or systemic heat stress are often used in combination with many active exercise programs. We designed a method to deliver a vibration stress and systemic heat stress to compare the effects with active skeletal muscle contraction. The purpose of this study is to examine whether active mechanical stress (muscle contraction), passive mechanical stress (vibration), or systemic whole body heat stress regulates key gene signatures associated with muscle metabolism, hypertrophy/atrophy, and inflammation/repair. Eleven subjects, six able-bodied and five with chronic spinal cord injury (SCI) participated in the study. The six able-bodied subjects sat in a heat stress chamber for 30 minutes. Five subjects with SCI received a single dose of limb-segment vibration or a dose of repetitive electrically induced muscle contractions. Three hours after the completion of each stress, we performed a muscle biopsy (vastus lateralis or soleus) to analyze mRNA gene expression. We discovered repetitive active muscle contractions up regulated metabolic transcription factors NR4A3 (12.45 fold), PGC-1α (5.46 fold), and ABRA (5.98 fold); and repressed MSTN (0.56 fold). Heat stress repressed PGC-1α (0.74 fold change; p muscle contraction. Vibration induced FOXK2 (p muscle contractions. Understanding these responses may assist in developing regenerative rehabilitation interventions to improve muscle cell development, growth, and repair.

  7. Syngeneic B16F10 Melanoma Causes Cachexia and Impaired Skeletal Muscle Strength and Locomotor Activity in Mice

    Directory of Open Access Journals (Sweden)

    Fabrício A. Voltarelli

    2017-09-01

    Full Text Available Muscle wasting has been emerging as one of the principal components of cancer cachexia, leading to progressive impairment of work capacity. Despite early stages melanomas rarely promotes weight loss, the appearance of metastatic and/or solid tumor melanoma can leads to cachexia development. Here, we investigated the B16F10 tumor-induced cachexia and its contribution to muscle strength and locomotor-like activity impairment. C57BL/6 mice were subcutaneously injected with 5 × 104 B16F10 melanoma cells or PBS as a Sham negative control. Tumor growth was monitored during a period of 28 days. Compared to Sham mice, tumor group depicts a loss of skeletal muscle, as well as significantly reduced muscle grip strength and epididymal fat mass. This data are in agreement with mild to severe catabolic host response promoted by elevated serum tumor necrosis factor-alpha (TNF-α, interleukin-6 (IL-6 and lactate dehydrogenase (LDH activity. Tumor implantation has also compromised general locomotor activity and decreased exploratory behavior. Likewise, muscle loss, and elevated inflammatory interleukin were associated to muscle strength loss and locomotor activity impairment. In conclusion, our data demonstrated that subcutaneous B16F10 melanoma tumor-driven catabolic state in response to a pro-inflammatory environment that is associated with impaired skeletal muscle strength and decreased locomotor activity in tumor-bearing mice.

  8. Activity of clinically relevant antimalarial drugs on Plasmodium falciparum mature gametocytes in an ATP bioluminescence "transmission blocking" assay.

    Directory of Open Access Journals (Sweden)

    Joël Lelièvre

    Full Text Available BACKGROUND: Current anti-malarial drugs have been selected on the basis of their activity against the symptom-causing asexual blood stage of the parasite. Which of these drugs also target gametocytes, in the sexual stage responsible for disease transmission, remains unknown. Blocking transmission is one of the main strategies in the eradication agenda and requires the identification of new molecules that are active against gametocytes. However, to date, the main limitation for measuring the effect of molecules against mature gametocytes on a large scale is the lack of a standardized and reliable method. Here we provide an efficient method to produce and purify mature gametocytes in vitro. Based on this new procedure, we developed a robust, affordable, and sensitive ATP bioluminescence-based assay. We then assessed the activity of 17 gold-standard anti-malarial drugs on Plasmodium late stage gametocytes. METHODS AND FINDINGS: Difficulties in producing large amounts of gametocytes have limited progress in the development of malaria transmission blocking assays. We improved the method established by Ifediba and Vanderberg to obtain viable, mature gametocytes en masse, whatever the strain used. We designed an assay to determine the activity of antimalarial drugs based on the intracellular ATP content of purified stage IV-V gametocytes after 48 h of drug exposure in 96/384-well microplates. Measurements of drug activity on asexual stages and cytotoxicity on HepG2 cells were also obtained to estimate the specificity of the active drugs. CONCLUSIONS: The work described here represents another significant step towards determination of the activity of new molecules on mature gametocytes of any strain with an automated assay suitable for medium/high-throughput screening. Considering that the biology of the forms involved in the sexual and asexual stages is very different, a screen of our 2 million-compound library may allow us to discover novel anti

  9. Exercise training and return to a well-balanced diet activate the neuregulin 1/ErbB pathway in skeletal muscle of obese rats.

    Science.gov (United States)

    Ennequin, Gaël; Boisseau, Nathalie; Caillaud, Kevin; Chavanelle, Vivien; Gerbaix, Maude; Metz, Lore; Etienne, Monique; Walrand, Stéphane; Masgrau, Aurélie; Guillet, Christelle; Courteix, Daniel; Niu, Airu; Li, Yi-Ping; Capel, Fréderic; Sirvent, Pascal

    2015-06-15

    Some studies suggest that neuregulin 1 (NRG1) could be involved in the regulation of skeletal muscle energy metabolism in rodents. Here we assessed whether unbalanced diet is associated with alterations of the NRG1 signalling pathway and whether exercise and diet might restore NRG1 signalling in skeletal muscle of obese rats. We show that diet-induced obesity does not impair NRG1 signalling in rat skeletal muscle. We also report that endurance training and a well-balanced diet activate the NRG1 signalling in skeletal muscle of obese rats, possibly via a new mechanism mediated by the protease ADAM17. These results suggest that some beneficial effects of physical activity and diet in obese rats could be partly explained by stimulation of the NRG1 signalling pathway. Some studies suggest that the signalling pathway of neuregulin 1 (NRG1), a protein involved in the regulation of skeletal muscle metabolism, could be altered by nutritional and exercise interventions. We hypothesized that diet-induced obesity could lead to alterations of the NRG1 signalling pathway and that chronic exercise could improve NRG1 signalling in rat skeletal muscle. To test this hypothesis, male Wistar rats received a high fat/high sucrose (HF/HS) diet for 16 weeks. At the end of this period, NRG1 and ErbB expression/activity in skeletal muscle was assessed. The obese rats then continued the HF/HS diet or were switched to a well-balanced diet. Moreover, in both groups, half of the animals also performed low intensity treadmill exercise training. After another 8 weeks, NRG1 and ErbB expression/activity in skeletal muscle were tested again. The 16 week HF/HS diet induced obesity, but did not significantly affect the NRG1/ErbB signalling pathway in rat skeletal muscle. Conversely, after the switch to a well-balanced diet, NRG1 cleavage ratio and ErbB4 amount were increased. Chronic exercise training also promoted NRG1 cleavage, resulting in increased ErbB4 phosphorylation. This result was

  10. A randomised trial of differentiated prednisolone treatment in active rheumatoid arthritis. Clinical benefits and skeletal side effects

    DEFF Research Database (Denmark)

    Hansen, M; Podenphant, J; Florescu, A

    1999-01-01

    OBJECTIVES: To study benefits and skeletal side effects of carefully monitored prednisolone treatment in patients with active rheumatoid arthritis. METHODS: One hundred and two patients with active rheumatoid arthritis were randomly allocated to treatment with disease modifying anti......-inflammatory drug (DMARD) alone or DMARD and prednisolone in a one year follow up study. Prednisolone was given in a dose regimen adapted to the disease activity of the individual patient. The mean dose was 6 mg and the mean cumulated dose was 2160 mg. Patients were followed up with disease activity parameters......, radiograph of the hands (Larsen score), and bone mineral density (BMD) of the lumbar spine, distal forearm and hand. At one year 26 patients had withdrawn from the investigation leaving 76 patients for evaluation. RESULTS: The results showed that disease activity in the prednisolone treated group was reduced...

  11. NRIP is newly identified as a Z-disc protein, activating calmodulin signaling for skeletal muscle contraction and regeneration.

    Science.gov (United States)

    Chen, Hsin-Hsiung; Chen, Wen-Pin; Yan, Wan-Lun; Huang, Yuan-Chun; Chang, Szu-Wei; Fu, Wen-Mei; Su, Ming-Jai; Yu, I-Shing; Tsai, Tzung-Chieh; Yan, Yu-Ting; Tsao, Yeou-Ping; Chen, Show-Li

    2015-11-15

    Nuclear receptor interaction protein (NRIP, also known as DCAF6 and IQWD1) is a Ca(2+)-dependent calmodulin-binding protein. In this study, we newly identify NRIP as a Z-disc protein in skeletal muscle. NRIP-knockout mice were generated and found to have reduced muscle strength, susceptibility to fatigue and impaired adaptive exercise performance. The mechanisms of NRIP-regulated muscle contraction depend on NRIP being downstream of Ca(2+) signaling, where it stimulates activation of both 'calcineurin-nuclear factor of activated T-cells, cytoplasmic 1' (CaN-NFATc1; also known as NFATC1) and calmodulin-dependent protein kinase II (CaMKII) through interaction with calmodulin (CaM), resulting in the induction of mitochondrial activity and the expression of genes encoding the slow class of myosin, and in the regulation of Ca(2+) homeostasis through the internal Ca(2+) stores of the sarcoplasmic reticulum. Moreover, NRIP-knockout mice have a delayed regenerative capacity. The amount of NRIP can be enhanced after muscle injury and is responsible for muscle regeneration, which is associated with the increased expression of myogenin, desmin and embryonic myosin heavy chain during myogenesis, as well as for myotube formation. In conclusion, NRIP is a novel Z-disc protein that is important for skeletal muscle strength and regenerative capacity. © 2015. Published by The Company of Biologists Ltd.

  12. Improvement of maternal vitamin D status with 25-hydroxycholecalciferol positively impacts porcine fetal skeletal muscle development and myoblast activity.

    Science.gov (United States)

    Hines, E A; Coffey, J D; Starkey, C W; Chung, T K; Starkey, J D

    2013-09-01

    There is little information available regarding the influence of maternal vitamin D status on fetal skeletal muscle development. Therefore, we investigated the effect of improved vitamin D status resulting from 25-hydroxycholecalciferol (25OHD3) supplementation of dams on fetal skeletal muscle developmental characteristics and myoblast activity using Camborough 22 gilts (n = 40) randomly assigned to 1 of 2 corn-soybean meal-based diets. The control diet (CTL) contained 2,500 IU cholecalciferol (D3)/kg diet, whereas the experimental diet contained 500 IU D3/kg diet plus 50 µg 25OHD3/kg diet. Gilts were fed 2.7 kg of their assigned diet once daily beginning 43 d before breeding through d 90 of gestation. On gestational d 90 (± 1), fetal LM and semitendinosus muscle samples were collected for analysis of developmental characteristics and myoblast activity, respectively. No treatment difference was observed in fetal LM cross-sectional area (P = 0.25). Fetuses from 25OHD3-supplemented gilts had more LM fibers (P = 0.04) that tended to be smaller in cross-sectional area compared with CTL fetuses (P = 0.11). A numerical increase in the total number of Pax7+ myoblasts was also observed in fetuses from 25OHD3-supplemented gilts (P = 0.12). Myoblasts derived from the muscles of fetuses from 25OHD3-fed dams displayed an extended proliferative phase in culture compared with those from fetuses of dams fed only D3 (P importance of maternal vitamin D status on the development of fetal skeletal muscle.

  13. Dexamethasone up-regulates skeletal muscle maximal Na+,K+ pump activity by muscle group specific mechanisms in humans

    DEFF Research Database (Denmark)

    Nordsborg, Nikolai; Goodmann, Craig; McKenna, Michael J.

    2005-01-01

    Dexamethasone, a widely clinically used glucocorticoid, increases human skeletal muscle Na+,K+ pump content, but the effects on maximal Na+,K+ pump activity and subunit specific mRNA are unknown. Ten healthy male subjects ingested dexamethasone for 5 days and the effects on Na+,K+ pump content......, maximal activity and subunit specific mRNA level (a1, a2, ß1, ß2, ß3) in deltoid and vastus lateralis muscle were investigated. Before treatment, maximal Na+,K+ pump activity, as well as a1, a2, ß1 and ß2 mRNA levels were higher (P ... increased Na+,K+ pump maximal activity in vastus lateralis and deltoid by 14 ± 7% (P Na+,K+ pump content by 18 ± 9% (P

  14. Role of adenosine 5'-monophosphate-activated protein kinase subunits in skeletal muscle mammalian target of rapamycin signaling

    DEFF Research Database (Denmark)

    Deshmukh, Atul S.; Treebak, Jonas Thue; Long, Yun Chau

    2008-01-01

    AMP-activated protein kinase (AMPK) is an important energy-sensing protein in skeletal muscle. Mammalian target of rapamycin (mTOR) mediates translation initiation and protein synthesis through ribosomal S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). AMPK...... activation reduces muscle protein synthesis by down-regulating mTOR signaling, whereas insulin mediates mTOR signaling via Akt activation. We hypothesized that AMPK-mediated inhibitory effects on mTOR signaling depend on catalytic alpha2 and regulatory gamma3 subunits. Extensor digitorum longus muscle from...... (Thr37/46) (P mTOR targets, suggesting mTOR signaling is blocked by prior AMPK activation. The AICAR-induced inhibition was partly rescued...

  15. Comparison of two methodologies to estimate microbial activity in a pumpkin crop (Cucurbita maxima) in blooming and maturity phases

    International Nuclear Information System (INIS)

    Cadena, Silvio F; Madrinan, Raul

    1999-01-01

    The measure of soil microbial activity is a significant feature in fertility and conservation diagnostic thinking about it, we compared two methodologies: volumetric Calcimeter that measures CO 2 released by soil into closed atmospheric system (glass tubes), cab method that retains CO 2 released during incubation phase in a closed system (glass bottles) at 23 degrades celsius subsequently titrate with HCL 0.5N. Results showed microbial activity in a pumpkin crop (Cucurbita maxima) in Palmira, Valle del Cauca - Colombia, is higher in maturity than blooming phase. It occurs beca use contribution of nutritive substances from pumpkin's roots as it is in physiological maturity and microclimate offered by full foliage of pumpkin. Because in CAB method, soil is put on trial with its natural wet the numeric results express as mgC-CO 2 .g 1 of soil are most reliable than volumetric Calcimeter method. The cost analysis showed that cab is twenty percent cheaper than volumetric Calcimeter method

  16. Nonspecific activation of murine lymphocytes. IV. Proliferation of a distinct, late maturing lymphocyte subpopulation induced by 2-mercaptoethanol

    International Nuclear Information System (INIS)

    Goodman, M.G.; Fidler, J.M.; Weigle, W.O.

    1978-01-01

    The lymphocyte subpopulations that are activated by 2-ME, LPS, poly IC, and PPD were studied in terms of their maturational characteristics. Attempts to stimulate hepatic and splenic lymphoid cells from mice of different ages with these mitogens demonstrated a well ordered sequence for the emergency of mitogen responsiveness in C3H mice: reactivity to LPS and Poly IC was observed early in maturation and was followed by that to PPD, and finally by the development of responsiveness to 2-ME. The same sequence appeared when the mitogen responsiveness of lethally irradiated, fetal liver-reconstituted syngeneic adult recipients was examined. The mitogenic action of 2-ME was dissociated from its ability to enhance lymphocyte reactivity to other mitogens in mice too young to respond to 2-ME as a mitogen. Experiments in which additivity of responses was assayed by adding mitogens to culture singly or conjointly indicated that LPS and Poly IC activate nearly identical B lymphocyte subpopulations, whereas PPD stimulates a subset of cells distinct from that which is responsive to the former two mitogens. The mitogen responsiveness of CBA/N mice, relative to normal CBA/WEHI mice, was shown to decrease as a function of the maturity of the subpopulation of lymphocytes activated. The CBA/N mouse was shown to be unresponsive to stimulation by 2-ME

  17. mTOR is necessary for proper satellite cell activity and skeletal muscle regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Pengpeng [Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry & Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States); Liang, Xinrong; Shan, Tizhong [Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States); Jiang, Qinyang [Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States); College of Animal Science and Technology, Guangxi University, Nanning 530004 (China); Deng, Changyan [Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry & Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Zheng, Rong, E-mail: zhengrong@mail.hzau.edu.cn [Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry & Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Kuang, Shihuan, E-mail: skuang@purdue.edu [Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States)

    2015-07-17

    The serine/threonine kinase mammalian target of rapamycin (mTOR) is a key regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive deletion of Mtor gene results in embryonic lethality, the function of mTOR in muscle stem cells (satellite cells) and skeletal muscle regeneration remains to be determined. In this study, we established a satellite cell specific Mtor conditional knockout (cKO) mouse model by crossing Pax7{sup CreER} and Mtor{sup flox/flox} mice. Skeletal muscle regeneration after injury was severely compromised in the absence of Mtor, indicated by increased number of necrotic myofibers infiltrated by Evans blue dye, and reduced number and size of regenerated myofibers in the Mtor cKO mice compared to wild type (WT) littermates. To dissect the cellular mechanism, we analyzed satellite cell-derived primary myoblasts grown on single myofibers or adhered to culture plates. The Mtor cKO myoblasts exhibited defective proliferation and differentiation kinetics when compared to myoblasts derived from WT littermates. At the mRNA and protein levels, the Mtor cKO myoblasts expressed lower levels of key myogenic determinant genes Pax7, Myf5, Myod, Myog than did the WT myoblasts. These results suggest that mTOR is essential for satellite cell function and skeletal muscle regeneration through controlling the expression of myogenic genes. - Highlights: • Pax7{sup CreER} was used to delete Mtor gene in satellite cells. • Satellite cell specific deletion of Mtor impairs muscle regeneration. • mTOR is necessary for satellite cell proliferation and differentiation. • Deletion of Mtor leads to reduced expression of key myogenic genes.

  18. Increased Stiffness in Aged Skeletal Muscle Impairs Muscle Progenitor Cell Proliferative Activity.

    Directory of Open Access Journals (Sweden)

    Grégory Lacraz

    Full Text Available Skeletal muscle aging is associated with a decreased regenerative potential due to the loss of function of endogenous stem cells or myogenic progenitor cells (MPCs. Aged skeletal muscle is characterized by the deposition of extracellular matrix (ECM, which in turn influences the biomechanical properties of myofibers by increasing their stiffness. Since the stiffness of the MPC microenvironment directly impacts MPC function, we hypothesized that the increase in muscle stiffness that occurs with aging impairs the behavior of MPCs, ultimately leading to a decrease in regenerative potential.We showed that freshly isolated individual myofibers from aged mouse muscles contain fewer MPCs overall than myofibers from adult muscles, with fewer quiescent MPCs and more proliferative and differentiating MPCs. We observed alterations in cultured MPC behavior in aged animals, where the proliferation and differentiation of MPCs were lower and higher, respectively. These alterations were not linked to the intrinsic properties of aged myofibers, as shown by the similar values for the cumulative population-doubling values and fusion indexes. However, atomic force microscopy (AFM indentation experiments revealed a nearly 4-fold increase in the stiffness of the MPC microenvironment. We further showed that the increase in stiffness is associated with alterations to muscle ECM, including the accumulation of collagen, which was correlated with higher hydroxyproline and advanced glycation end-product content. Lastly, we recapitulated the impaired MPC behavior observed in aging using a hydrogel substrate that mimics the stiffness of myofibers.These findings provide novel evidence that the low regenerative potential of aged skeletal muscle is independent of intrinsic MPC properties but is related to the increase in the stiffness of the MPC microenvironment.

  19. mTOR is necessary for proper satellite cell activity and skeletal muscle regeneration

    International Nuclear Information System (INIS)

    Zhang, Pengpeng; Liang, Xinrong; Shan, Tizhong; Jiang, Qinyang; Deng, Changyan; Zheng, Rong; Kuang, Shihuan

    2015-01-01

    The serine/threonine kinase mammalian target of rapamycin (mTOR) is a key regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive deletion of Mtor gene results in embryonic lethality, the function of mTOR in muscle stem cells (satellite cells) and skeletal muscle regeneration remains to be determined. In this study, we established a satellite cell specific Mtor conditional knockout (cKO) mouse model by crossing Pax7 CreER and Mtor flox/flox mice. Skeletal muscle regeneration after injury was severely compromised in the absence of Mtor, indicated by increased number of necrotic myofibers infiltrated by Evans blue dye, and reduced number and size of regenerated myofibers in the Mtor cKO mice compared to wild type (WT) littermates. To dissect the cellular mechanism, we analyzed satellite cell-derived primary myoblasts grown on single myofibers or adhered to culture plates. The Mtor cKO myoblasts exhibited defective proliferation and differentiation kinetics when compared to myoblasts derived from WT littermates. At the mRNA and protein levels, the Mtor cKO myoblasts expressed lower levels of key myogenic determinant genes Pax7, Myf5, Myod, Myog than did the WT myoblasts. These results suggest that mTOR is essential for satellite cell function and skeletal muscle regeneration through controlling the expression of myogenic genes. - Highlights: • Pax7 CreER was used to delete Mtor gene in satellite cells. • Satellite cell specific deletion of Mtor impairs muscle regeneration. • mTOR is necessary for satellite cell proliferation and differentiation. • Deletion of Mtor leads to reduced expression of key myogenic genes

  20. Lung injury-dependent oxidative status and chymotrypsin-like activity of skeletal muscles in hamsters with experimental emphysema

    Directory of Open Access Journals (Sweden)

    Tonon Jair

    2013-01-01

    Full Text Available Abstract Background Peripheral skeletal muscle is altered in patients suffering from emphysema and chronic obstructive pulmonary disease (COPD. Oxidative stress have been demonstrated to participate on skeletal muscle loss of several states, including disuse atrophy, mechanical ventilation, and chronic diseases. No evidences have demonstrated the occurance in a severity manner. Methods We evaluated body weight, muscle loss, oxidative stress, and chymotrypsin-like proteolytic activity in the gastrocnemius muscle of emphysemic hamsters. The experimental animals had 2 different severities of lung damage from experimental emphysema induced by 20 mg/mL (E20 and 40 mg/mL (E40 papain. Results The severity of emphysema increased significantly in E20 (60.52 ± 2.8, p Conclusions Taken together, the results of the present study suggest that muscle atrophy observed in this model of emphysema is mediated by increased muscle chymotrypsin-like activity, with possible involvement of oxidative stress in a severity-dependent manner.

  1. Quantifying disease activity in fatty-infiltrated skeletal muscle by IDEAL-CPMG in Duchenne muscular dystrophy.

    Science.gov (United States)

    Mankodi, Ami; Bishop, Courtney A; Auh, Sungyoung; Newbould, Rexford D; Fischbeck, Kenneth H; Janiczek, Robert L

    2016-10-01

    The purpose of this study was to explore the use of iterative decomposition of water and fat with echo asymmetry and least-squares estimation Carr-Purcell-Meiboom-Gill (IDEAL-CPMG) to simultaneously measure skeletal muscle apparent fat fraction and water T 2 (T 2,w ) in patients with Duchenne muscular dystrophy (DMD). In twenty healthy volunteer boys and thirteen subjects with DMD, thigh muscle apparent fat fraction was measured by Dixon and IDEAL-CPMG, with the IDEAL-CPMG also providing T 2,w as a measure of muscle inflammatory activity. A subset of subjects with DMD was followed up during a 48-week clinical study. The study was in compliance with the Patient Privacy Act and approved by the Institutional Review Board. Apparent fat fraction in the thigh muscles of subjects with DMD was significantly increased compared to healthy volunteer boys (p Muscle T 2,w measured by IDEAL-CPMG was independent of changes in apparent fat fraction. Muscle T 2,w was higher in the biceps femoris and vastus lateralis muscles of subjects with DMD (p muscles and six-minute walk distance (6MWD) in subjects with DMD. IDEAL-CPMG allowed independent and simultaneous quantification of skeletal muscle fatty degeneration and disease activity in DMD. IDEAL-CPMG apparent fat fraction and T 2,w may be useful as biomarkers in clinical trials of DMD as the technique disentangles two competing biological processes. Published by Elsevier B.V.

  2. α-smooth muscle actin is not a marker of fibrogenic cell activity in skeletal muscle fibrosis.

    Directory of Open Access Journals (Sweden)

    Wanming Zhao

    Full Text Available α-Smooth muscle actin (α-SMA is used as a marker for a subset of activated fibrogenic cells, myofibroblasts, which are regarded as important effector cells of tissue fibrogenesis. We address whether α-SMA-expressing myofibroblasts are detectable in fibrotic muscles of mdx5cv mice, a mouse model for Duchenne muscular dystrophy (DMD, and whether the α-SMA expression correlates with the fibrogenic function of intramuscular fibrogenic cells. α-SMA immunostaining signal was not detected in collagen I (GFP-expressing cells in fibrotic muscles of ColI-GFP/mdx5cv mice, but it was readily detected in smooth muscle cells lining intramuscular blood vessel walls. α-SMA expression was detected by quantitative RT-PCR and Western blot in fibrogenic cells sorted from diaphragm and quadriceps muscles of the ColI-GFP/mdx5cv mice. Consistent with the more severe fibrosis in the ColI-GFP/mdx5cv diaphragm, the fibrogenic cells in the diaphragm exerted a stronger fibrogenic function than the fibrogenic cells in the quadriceps as gauged by their extracellular matrix gene expression. However, both gene and protein expression of α-SMA was lower in the diaphragm fibrogenic cells than in the quadriceps fibrogenic cells in the ColI-GFP/mdx5cv mice. We conclude that myofibroblasts are present in fibrotic skeletal muscles, but their expression of α-SMA is not detectable by immunostaining. The level of α-SMA expression by intramuscular fibrogenic cells does not correlate positively with the level of collagen gene expression or the severity of skeletal muscle fibrosis in the mdx5cv mice. α-SMA is not a functional marker of fibrogenic cells in skeletal muscle fibrosis associated with muscular dystrophy.

  3. ALUMINUM CHLORIDE EFFECT ON Ca2+,Mg(2+)-ATPase ACTIVITY AND DYNAMIC PARAMETERS OF SKELETAL MUSCLE CONTRACTION.

    Science.gov (United States)

    Nozdrenko, D M; Abramchuk, O M; Soroca, V M; Miroshnichenko, N S

    2015-01-01

    We studied enzymatic activity and measured strain-gauge contraction properties of the frog Rana temporaria m. tibialis anterior muscle fascicles during the action of aluminum chloride solution. It was shown that AlCl3 solutions did not affect the dynamic properties of skeletal muscle preparation in concentrations less than 10(-4) M Increasing the concentration of AlCl3 to 10(-2) M induce complete inhibition of muscle contraction. A linear correlation between decrease in Ca2+,Mg(2+)-ATPase activity of sarcoplasmic reticulum and the investigated concentrations range of aluminum chloride was observed. The reduction in the dynamic contraction performance and the decrease Ca2+,Mg(2+)-ATPase activity of the sarcoplasmic reticulum under the effect of the investigated AlCl3 solution were minimal in pre-tetanus period of contraction.

  4. Aluminum chloride effect on Ca(2+,Mg(2+-ATPase activity and dynamic parameters of skeletal muscle contraction

    Directory of Open Access Journals (Sweden)

    D. M. Nozdrenko

    2015-10-01

    Full Text Available We studied enzymatic activity and measured strain-gauge contraction properties of the frog Rana temporaria m. tibialis anterior muscle fascicles during the action of aluminum chloride solution. It was shown that AlCl3 solutions did not affect the dynamic properties of skeletal muscle preparation in concentrations less than 10-4 M. Increasing the concentration of AlCl3 to 10-2 M induce complete inhibition of muscle contraction. A linear correlation between decrease in Ca2+,Mg2+-ATPase activity of sarcoplasmic reticulum and the investigated concentrations range of aluminum chloride was observed. The reduction in the dynamic contraction performance and the decrease Ca2+,Mg2+-ATPase activity of the sarcoplasmic reticulum under the effect of the investigated AlCl3 solution were minimal in pre-tetanus period of contraction.

  5. Physical activity opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Mortensen, Stefan Peter; Hellsten, Ylva

    2013-01-01

    performed lifelong physical activity had similar plasma and muscle endothelin-1 levels as the young controls and had higher ET(A) receptor levels. CONCLUSION: Our findings suggest that aerobic exercise training opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes......AIMS: Endothelin-1 has potent constrictor and proliferative activity in vascular smooth muscle, and essential hypertension and aging are associated with increased endothelin-1-mediated vasoconstrictor tone. The aim of this study was to investigate the effect of physical activity, hypertension...... and age on endothelin-1 levels in plasma and skeletal muscle and endothelin receptors in skeletal muscle in human subjects. METHODS: In study 1, normotensive (46 ± 1 years, n = 11) and hypertensive (47 ± 1 years, n = 10) subjects were studied before and after 8 weeks of aerobic exercise training. In study...

  6. Mouse senile amyloid fibrils deposited in skeletal muscle exhibit amyloidosis-enhancing activity.

    Directory of Open Access Journals (Sweden)

    Jinze Qian

    2010-05-01

    Full Text Available Amyloidosis describes a group of protein folding diseases in which amyloid proteins are abnormally deposited in organs and/or tissues as fine fibrils. Mouse senile amyloidosis is a disorder in which apolipoprotein A-II (apoA-II deposits as amyloid fibrils (AApoAII and can be transmitted from one animal to another both by the feces and milk excreted by mice with amyloidosis. Thus, mouse AApoAII amyloidosis has been demonstrated to be a "transmissible disease". In this study, to further characterize the transmissibility of amyloidosis, AApoAII amyloid fibrils were injected into transgenic Apoa2(cTg(+/- and normal R1.P1-Apoa2(c mice to induce AApoAII systemic amyloidosis. Two months later, AApoAII amyloid deposits were found in the skeletal muscles of amyloid-affected mice, primarily in the blood vessels and in the interstitial tissues surrounding muscle fibers. When amyloid fibrils extracted from the skeletal muscles were subjected to Western blot analysis, apoA-II was detected. Amyloid fibril fractions isolated from the muscles not only demonstrated the structure of amyloid fibrils but could also induce amyloidosis in young mice depending on its fibril conformation. These findings present a possible pathogenesis of amyloidosis: transmission of amyloid fibril conformation through muscle, and shed new light on the etiology involved in amyloid disorders.

  7. Characterization of odor-active volatiles in apples: influence of cultivars and maturity stage.

    Science.gov (United States)

    Mehinagic, Emira; Royer, Gaëlle; Symoneaux, Ronan; Jourjon, Frédérique; Prost, Carole

    2006-04-05

    The aroma and texture of three different apple cultivars, harvested at three maturity stages, were analyzed by sensory and instrumental analysis. The emphasis was on the identification of the most potent odorant volatiles, and the challenge was to separate the few most important flavor compounds, which may be trace chemicals, from the vast number of nonodorant compounds present in apple aroma extracts. Thirty-six odorant compounds were detected, 24 of which were common to all extracts. A significant correlation coefficient was found between the aroma intensity scores and overall quantity of the odorant volatiles, which shows that the development of sensory aroma is similar to that of odorant volatiles. This study also showed that the parameters measured by penetrometry and compression were highly correlated with sensory textural attributes. The determination of the optimal maturity stage for different apple cultivars by the usual parameters, such as color, diameter, total soluble solids, and titrable acidity, may not be sufficient to determine the optimal sensory quality for consumers. Moreover, the sensory quality of fruits changes during maturation in a different way from one cultivar to another, and this should be taken into account.

  8. Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans.

    Directory of Open Access Journals (Sweden)

    Michael A Petrie

    Full Text Available Skeletal muscle exercise regulates several important metabolic genes in humans. We know little about the effects of environmental stress (heat and mechanical stress (vibration on skeletal muscle. Passive mechanical stress or systemic heat stress are often used in combination with many active exercise programs. We designed a method to deliver a vibration stress and systemic heat stress to compare the effects with active skeletal muscle contraction.The purpose of this study is to examine whether active mechanical stress (muscle contraction, passive mechanical stress (vibration, or systemic whole body heat stress regulates key gene signatures associated with muscle metabolism, hypertrophy/atrophy, and inflammation/repair.Eleven subjects, six able-bodied and five with chronic spinal cord injury (SCI participated in the study. The six able-bodied subjects sat in a heat stress chamber for 30 minutes. Five subjects with SCI received a single dose of limb-segment vibration or a dose of repetitive electrically induced muscle contractions. Three hours after the completion of each stress, we performed a muscle biopsy (vastus lateralis or soleus to analyze mRNA gene expression.We discovered repetitive active muscle contractions up regulated metabolic transcription factors NR4A3 (12.45 fold, PGC-1α (5.46 fold, and ABRA (5.98 fold; and repressed MSTN (0.56 fold. Heat stress repressed PGC-1α (0.74 fold change; p < 0.05; while vibration induced FOXK2 (2.36 fold change; p < 0.05. Vibration similarly caused a down regulation of MSTN (0.74 fold change; p < 0.05, but to a lesser extent than active muscle contraction. Vibration induced FOXK2 (p < 0.05 while heat stress repressed PGC-1α (0.74 fold and ANKRD1 genes (0.51 fold; p < 0.05.These findings support a distinct gene regulation in response to heat stress, vibration, and muscle contractions. Understanding these responses may assist in developing regenerative rehabilitation interventions to improve muscle cell

  9. Leucine stimulates protein synthesis in skeletal muscle of neonatal pigs by enhancing mTORC1 activation.

    Science.gov (United States)

    Suryawan, Agus; Jeyapalan, Asumthia S; Orellana, Renan A; Wilson, Fiona A; Nguyen, Hanh V; Davis, Teresa A

    2008-10-01

    Skeletal muscle in the neonate grows at a rapid rate due in part to an enhanced sensitivity to the postprandial rise in amino acids, particularly leucine. To elucidate the molecular mechanism by which leucine stimulates protein synthesis in neonatal muscle, overnight-fasted 7-day-old piglets were treated with rapamycin [an inhibitor of mammalian target of rapamycin (mTOR) complex (mTORC)1] for 1 h and then infused with leucine for 1 h. Fractional rates of protein synthesis and activation of signaling components that lead to mRNA translation were determined in skeletal muscle. Rapamycin completely blocked leucine-induced muscle protein synthesis. Rapamycin markedly reduced raptor-mTOR association, an indicator of mTORC1 activation. Rapamycin blocked the leucine-induced phosphorylation of mTOR, S6 kinase 1 (S6K1), and eukaryotic initiation factor (eIF)4E-binding protein-1 (4E-BP1) and formation of the eIF4E.eIF4G complex and increased eIF4E.4E-BP1 complex abundance. Rapamycin had no effect on the association of mTOR with rictor, a crucial component for mTORC2 activation, or G protein beta-subunit-like protein (GbetaL), a component of mTORC1 and mTORC2. Neither leucine nor rapamycin affected the phosphorylation of AMP-activated protein kinase (AMPK), PKB, or tuberous sclerosis complex (TSC)2, signaling components that reside upstream of mTOR. Eukaryotic elongation factor (eEF)2 phosphorylation was not affected by leucine or rapamycin, although current dogma indicates that eEF2 phosphorylation is mTOR dependent. Together, these in vivo data suggest that leucine stimulates muscle protein synthesis in neonates by enhancing mTORC1 activation and its downstream effectors.

  10. NKT Cell-TCR Expression Activates Conventional T Cells in Vivo, but Is Largely Dispensable for Mature NKT Cell Biology

    Science.gov (United States)

    Vahl, J. Christoph; Heger, Klaus; Knies, Nathalie; Hein, Marco Y.; Boon, Louis; Yagita, Hideo; Polic, Bojan; Schmidt-Supprian, Marc

    2013-01-01

    Natural killer T (NKT) cell development depends on recognition of self-glycolipids via their semi-invariant Vα14i-TCR. However, to what extent TCR-mediated signals determine identity and function of mature NKT cells remains incompletely understood. To address this issue, we developed a mouse strain allowing conditional Vα14i-TCR expression from within the endogenous Tcrα locus. We demonstrate that naïve T cells are activated upon replacement of their endogenous TCR repertoire with Vα14i-restricted TCRs, but they do not differentiate into NKT cells. On the other hand, induced TCR ablation on mature NKT cells did not affect their lineage identity, homeostasis, or innate rapid cytokine secretion abilities. We therefore propose that peripheral NKT cells become unresponsive to and thus are independent of their autoreactive TCR. PMID:23853545

  11. NKT cell-TCR expression activates conventional T cells in vivo, but is largely dispensable for mature NKT cell biology.

    Directory of Open Access Journals (Sweden)

    J Christoph Vahl

    Full Text Available Natural killer T (NKT cell development depends on recognition of self-glycolipids via their semi-invariant Vα14i-TCR. However, to what extent TCR-mediated signals determine identity and function of mature NKT cells remains incompletely understood. To address this issue, we developed a mouse strain allowing conditional Vα14i-TCR expression from within the endogenous Tcrα locus. We demonstrate that naïve T cells are activated upon replacement of their endogenous TCR repertoire with Vα14i-restricted TCRs, but they do not differentiate into NKT cells. On the other hand, induced TCR ablation on mature NKT cells did not affect their lineage identity, homeostasis, or innate rapid cytokine secretion abilities. We therefore propose that peripheral NKT cells become unresponsive to and thus are independent of their autoreactive TCR.

  12. Activation of Cyclic AMP Synthesis by Full and Partial Beta-Adrenergic Receptor Agonists in Chicken Skeletal Muscle Cells

    Science.gov (United States)

    Young, R. B.; Bridge, K. Y.

    2003-01-01

    Several beta-adrenergic receptor (bAR) agonists are known to cause hypertrophy of skeletal muscle tissue. Accordingly, five bAR agonists encompassing a range in activity from strong to weak were evaluated for their ability to stimulate CAMP accumulation in embryonic chicken skeletal muscle cells in culture. Two strong agonists (epinephrine and isoproterenol), one moderate agonist (albuterol), and two weak agonists known to cause hypertrophy in animals (clenbuterol and cimaterol) were studied. Dose response curves were determined over six orders of magnitude in concentration for each agonist, and values were determined for their maximum stimulation of CAMP synthesis rate (Bmax) and the agonist concentration at which 50% stimulation of CAMP synthesis (EC50) occurred. Bmax values decreased in the following order: isoproterenol, epinephrine, albuterol, cimaterol, clenbuterol. Cimaterol and clenbuterol at their Bmax concentrations were approximately 15-fold weaker than isoproterenol in stimulating the rate of CAMP synthesis. When cimaterol and clenbuterol were added to culture media at concentrations known to cause significant muscle hypertrophy in animals, there was no detectable effect on stimulation of CAMP synthesis. Finally, these same levels of cimaterol and clenbuterol did not antagonize the stimulation of CAMP by either epinephrine or isoproterenol.

  13. Skeletal muscle protease activities in the early growth and development of wild Atlantic salmon (Salmo salar L.).

    Science.gov (United States)

    Lysenko, Liudmila A; Kantserova, Nadezda P; Kaivarainen, Elena I; Krupnova, Marina Yu; Nemova, Nina N

    2017-09-01

    Growth-related dynamics of intracellular protease activities in four year classes of the Atlantic salmon (Salmo salar L. 1758) parr and smolts inhabiting salmon rivers of northwestern Russia (the White Sea basin) were studied. Cathepsin B, cathepsin D, proteasome, and calpain activities in the skeletal muscles of salmon were assessed to investigate their relative contribution to the total protein degradation as well as to young fish growth process. It was confirmed that calpain activity dominates in salmon muscles while proteasome plays a minor role, in contrast to terrestrial vertebrates. Calpain and proteasome activities were maximal at the early post-larval stage (in parrs 0+) and declined with age (parrs 1+ through 2+) dropping to the lowest level in salmon smolts. Annual growth increments and proteolytic activities of calpains and proteasome in the muscles of salmon juveniles changed with age in an orchestrated manner, while lysosomal cathepsin activities increased with age. Comparing protease activities and growth increments in salmon parr and smolts we suggested that the partial suppression of the protein degradation could be a mechanism stimulating efficient growth in smoltifying salmon. Growth and smoltification-related dynamics of protease activities was quite similar in salmon populations from studied spawning rivers, such as Varzuga and Indera; however, some habitat-related differences were observed. Growth increments and protease activities varied in salmon parr 0+ (but not on later ages) inhabiting either main rivers or small tributaries apparently due to habitat difference on the resources for fish growth. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Insulin receptor binding and tyrosine kinase activity in skeletal muscle from normal pregnant women and women with gestational diabetes

    DEFF Research Database (Denmark)

    Damm, P.; Handberg, A.; Kühl, C.

    1993-01-01

    OBJECTIVE: To ascertain whether the decreased glucose tolerance and insulin resistance found in normal and gestational diabetic pregnancy might be associated with changes in insulin receptor function. METHODS: Eight nonpregnant healthy women (nonpregnant controls), eight healthy pregnant women...... (pregnant controls), and eight women with gestational diabetes were investigated. All were non-obese. Muscle biopsies were obtained from the vastus lateralis muscle, and insulin binding and tyrosine kinase activities in partially purified skeletal muscle insulin receptors were studied. The pregnant controls...... with gestational diabetes compared to nonpregnant controls (P pregnant women did not differ from the other two groups. Postpartum, no differences in insulin binding were found between the groups. Basal and maximal tyrosine kinase activities toward the exogenous substrate poly(Glu4Tyr1) were...

  15. The optimal period of Ca-EDTA treatment for parthenogenetic activation of porcine oocytes during maturation culture

    OpenAIRE

    MORITA, Yasuhiro; TANIGUCHI, Masayasu; TANIHARA, Fuminori; ITO, Aya; NAMULA, Zhao; DO, Lanh Thi Kim; TAKAGI, Mitsuhiro; TAKEMOTO, Tatsuya; OTOI, Takeshige

    2016-01-01

    The changes triggered by sperm-induced activation of oocytes, which are required for normal oocyte development, can be mediated by other agents, thereby inducing the parthenogenesis. In this study, we exposed porcine oocytes to 1 mM Ca-EDTA, a metal-ion chelator, at various intervals during 48 hr of in vitro maturation to determine the optimum period of Ca-EDTA treatment for parthenogenetic activation. When the oocytes were cultured with or without Ca-EDTA from 36 hr (post-12), 24 hr (post-24...

  16. Exercise training and return to a well-balanced diet activate the neuregulin 1/ErbB pathway in skeletal muscle of obese rats

    Science.gov (United States)

    Ennequin, Gaël; Boisseau, Nathalie; Caillaud, Kevin; Chavanelle, Vivien; Gerbaix, Maude; Metz, Lore; Etienne, Monique; Walrand, Stéphane; Masgrau, Aurélie; Guillet, Christelle; Courteix, Daniel; Niu, Airu; Li, Yi-Ping; Capel, Fréderic; Sirvent, Pascal

    2015-01-01

    Some studies suggest that the signalling pathway of neuregulin 1 (NRG1), a protein involved in the regulation of skeletal muscle metabolism, could be altered by nutritional and exercise interventions. We hypothesized that diet-induced obesity could lead to alterations of the NRG1 signalling pathway and that chronic exercise could improve NRG1 signalling in rat skeletal muscle. To test this hypothesis, male Wistar rats received a high fat/high sucrose (HF/HS) diet for 16 weeks. At the end of this period, NRG1 and ErbB expression/activity in skeletal muscle was assessed. The obese rats then continued the HF/HS diet or were switched to a well-balanced diet. Moreover, in both groups, half of the animals also performed low intensity treadmill exercise training. After another 8 weeks, NRG1 and ErbB expression/activity in skeletal muscle were tested again. The 16 week HF/HS diet induced obesity, but did not significantly affect the NRG1/ErbB signalling pathway in rat skeletal muscle. Conversely, after the switch to a well-balanced diet, NRG1 cleavage ratio and ErbB4 amount were increased. Chronic exercise training also promoted NRG1 cleavage, resulting in increased ErbB4 phosphorylation. This result was associated with increased protein expression and phosphorylation ratio of the metalloprotease ADAM17, which is involved in NRG1 shedding. Similarly, in vitro stretch-induced activation of ADAM17 in rat myoblasts induced NRG1 cleavage and ErbB4 activation. These results show that low intensity endurance training and well-balanced diet activate the NRG1-ErbB4 pathway, possibly via the metalloprotease ADAM17, in skeletal muscle of diet-induced obese rats. PMID:25820551

  17. Effect of voluntary physical activity initiated at age 7 months on skeletal hindlimb and cardiac muscle function in mdx mice of both genders.

    Science.gov (United States)

    Ferry, Arnaud; Benchaouir, Rachid; Joanne, Pierre; Peat, Rachel A; Mougenot, Nathalie; Agbulut, Onnik; Butler-Browne, Gillian

    2015-11-01

    The effects of voluntary activity initiated in adult mdx (C57BL/10ScSc-DMD(mdx) /J) mice on skeletal and cardiac muscle function have not been studied extensively. We studied the effects of 3 months of voluntary wheel running initiated at age 7 months on hindlimb muscle weakness, increased susceptibility to muscle contraction-induced injury, and left ventricular function in mdx mice. We found that voluntary wheel running did not worsen the deficit in force-generating capacity and the force drop after lengthening contractions in either mdx mouse gender. It increased the absolute maximal force of skeletal muscle in female mdx mice. Moreover, it did not affect left ventricular function, structural heart dimensions, cardiac gene expression of inflammation, fibrosis, or remodeling markers. These results indicate that voluntary activity initiated at age 7 months had no detrimental effects on skeletal or cardiac muscles in either mdx mouse gender. © 2015 Wiley Periodicals, Inc.

  18. Direct optical activation of skeletal muscle fibres efficiently controls muscle contraction and attenuates denervation atrophy.

    Science.gov (United States)

    Magown, Philippe; Shettar, Basavaraj; Zhang, Ying; Rafuse, Victor F

    2015-10-13

    Neural prostheses can restore meaningful function to paralysed muscles by electrically stimulating innervating motor axons, but fail when muscles are completely denervated, as seen in amyotrophic lateral sclerosis, or after a peripheral nerve or spinal cord injury. Here we show that channelrhodopsin-2 is expressed within the sarcolemma and T-tubules of skeletal muscle fibres in transgenic mice. This expression pattern allows for optical control of muscle contraction with comparable forces to nerve stimulation. Force can be controlled by varying light pulse intensity, duration or frequency. Light-stimulated muscle fibres depolarize proportionally to light intensity and duration. Denervated triceps surae muscles transcutaneously stimulated optically on a daily basis for 10 days show a significant attenuation in atrophy resulting in significantly greater contractile forces compared with chronically denervated muscles. Together, this study shows that channelrhodopsin-2/H134R can be used to restore function to permanently denervated muscles and reduce pathophysiological changes associated with denervation pathologies.

  19. Skeletal muscles of aged male mice fail to adapt following contractile activity.

    Science.gov (United States)

    Vasilaki, A; Iwanejko, L M; McArdle, F; Broome, C S; Jackson, M J; McArdle, A

    2003-04-01

    Skeletal muscle adapts rapidly following exercise by the increased production of heat-shock proteins (HSPs). The aim of this study was to examine the ability of muscle from adult and aged mice to produce HSPs following non-damaging exercise. Adult and aged B6XSJL mice were anaesthetized and their hind limbs were subjected to isometric contractions. At different time points, muscles were analysed for HSP production by Western and Northern blotting and by electrophoretic mobility-shift assay. HSP protein and mRNA levels in muscles from adult mice increased significantly following exercise. This was not evident in muscles of aged mice. In contrast, binding of the transcription factor heat-shock factor 1 (HSF1) was not grossly altered in muscles of aged mice compared with adult mice. The data suggest that the inability of muscles of aged mice to produce HSPs appears to be due to alterations during gene transcription.

  20. The Drosophila KIF1A homolog unc-104 is important for site-specific active zone maturation

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    Yao V. Zhang

    2016-09-01

    Full Text Available Abstract Mutations in the kinesin-3 family member KIF1A have been associated with hereditary spastic paraplegia, hereditary sensory and autonomic neuropathy type 2 and intellectual disability. Both autosomal recessive and autosomal dominant forms of inheritance have been reported. Loss of KIF1A or its homolog unc-104 causes early postnatal or embryonic lethality in mice and Drosophila, respectively. In this study we use a previously described hypomorphic allele of unc-104, unc-104bris, to investigate the impact of partial loss-of-function of kinesin-3 function on active zone formation at the Drosophila neuromuscular junction. unc-104bris mutants exhibit synaptic defects where a subset of synapses at the neuromuscular junction lack the key active zone organizer protein Bruchpilot. Modulating synaptic Bruchpilot levels by ectopic overexpression or RNAi-mediated knockdown suggests that the loss of active zone components such as Ca2+ channel and Liprin-α from these synapses is caused by impaired kinesin-3 transport rather than due to the absence of Bruchpilot at these synapses. In addition to defects in active zone maturation, unc-104bris mutants display impaired transport of dense core vesicles and synaptic vesicle associated proteins, among which Rab3 has been shown to regulate the distribution of Bruchpilot to active zones. Overexpression of Rab3 partially ameliorates synaptic phenotypes of unc-104bris neuromuscular junction, suggesting that lack of presynaptic Rab3 may contribute to defects in synapse maturation.

  1. Abnormal functional activation and maturation of ventromedial prefrontal cortex and cerebellum during temporal discounting in autism spectrum disorder.

    Science.gov (United States)

    Murphy, Clodagh M; Christakou, Anastasia; Giampietro, Vincent; Brammer, Michael; Daly, Eileen M; Ecker, Christine; Johnston, Patrick; Spain, Debbie; Robertson, Dene M; Murphy, Declan G; Rubia, Katya

    2017-11-01

    People with autism spectrum disorder (ASD) have poor decision-making and temporal foresight. This may adversely impact on their everyday life, mental health, and productivity. However, the neural substrates underlying poor choice behavior in people with ASD, or its' neurofunctional development from childhood to adulthood, are unknown. Despite evidence of atypical structural brain development in ASD, investigation of functional brain maturation in people with ASD is lacking. This cross-sectional developmental fMRI study investigated the neural substrates underlying performance on a temporal discounting (TD) task in 38 healthy (11-35 years old) male adolescents and adults with ASD and 40 age, sex, and IQ-matched typically developing healthy controls. Most importantly, we assessed group differences in the neurofunctional maturation of TD across childhood and adulthood. Males with ASD had significantly poorer task performance and significantly lower brain activation in typical regions that mediate TD for delayed choices, in predominantly right hemispheric regions of ventrolateral/dorsolateral prefrontal cortices, ventromedial prefrontal cortex, striatolimbic regions, and cerebellum. Importantly, differential activation in ventromedial frontal cortex and cerebellum was associated with abnormal functional brain maturation; controls, in contrast to people with ASD, showed progressively increasing activation with increasing age in these regions; which furthermore was associated with performance measures and clinical ASD measures (stereotyped/restricted interests). Findings provide first cross-sectional evidence that reduced activation of TD mediating brain regions in people with ASD during TD is associated with abnormal functional brain development in these regions between childhood and adulthood, and this is related to poor task performance and clinical measures of ASD. Hum Brain Mapp 38:5343-5355, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  2. Correlation between cervical vertebral and dental maturity in Iranian subjects.

    Science.gov (United States)

    Heravi, Farzin; Imanimoghaddam, Mahrokh; Rahimi, Hoda

    2011-12-01

    Determination of the skeletal maturation is extremely important in clinical orthodontics. Cervical vertebral maturation is an effective diagnostic tool for determining the adolescent growth spurt. The aim of this study was to investigate the correlation between the stages of calcification of teeth and the cervical vertebral maturity stages.

  3. STAT3 Activation in Skeletal Muscle Links Muscle Wasting and the Acute Phase Response in Cancer Cachexia

    Science.gov (United States)

    Kunzevitzky, Noelia; Guttridge, Denis C.; Khuri, Sawsan; Koniaris, Leonidas G.; Zimmers, Teresa A.

    2011-01-01

    Background Cachexia, or weight loss despite adequate nutrition, significantly impairs quality of life and response to therapy in cancer patients. In cancer patients, skeletal muscle wasting, weight loss and mortality are all positively associated with increased serum cytokines, particularly Interleukin-6 (IL-6), and the presence of the acute phase response. Acute phase proteins, including fibrinogen and serum amyloid A (SAA) are synthesized by hepatocytes in response to IL-6 as part of the innate immune response. To gain insight into the relationships among these observations, we studied mice with moderate and severe Colon-26 (C26)-carcinoma cachexia. Methodology/Principal Findings Moderate and severe C26 cachexia was associated with high serum IL-6 and IL-6 family cytokines and highly similar patterns of skeletal muscle gene expression. The top canonical pathways up-regulated in both were the complement/coagulation cascade, proteasome, MAPK signaling, and the IL-6 and STAT3 pathways. Cachexia was associated with increased muscle pY705-STAT3 and increased STAT3 localization in myonuclei. STAT3 target genes, including SOCS3 mRNA and acute phase response proteins, were highly induced in cachectic muscle. IL-6 treatment and STAT3 activation both also induced fibrinogen in cultured C2C12 myotubes. Quantitation of muscle versus liver fibrinogen and SAA protein levels indicates that muscle contributes a large fraction of serum acute phase proteins in cancer. Conclusions/Significance These results suggest that the STAT3 transcriptome is a major mechanism for wasting in cancer. Through IL-6/STAT3 activation, skeletal muscle is induced to synthesize acute phase proteins, thus establishing a molecular link between the observations of high IL-6, increased acute phase response proteins and muscle wasting in cancer. These results suggest a mechanism by which STAT3 might causally influence muscle wasting by altering the profile of genes expressed and translated in muscle such

  4. ORGANIZATIONAL PROJECT MANAGEMENT MATURITY

    Directory of Open Access Journals (Sweden)

    Yana Derenskaya

    2017-11-01

    Full Text Available The present article is aimed at developing a set of recommendations for achieving a higher level of organizational project maturity at a given enterprise. Methodology. For the purposes of the current research, the available information sources on the components of project management system are analysed; the essence of “organizational maturity” and the existing models of organizational maturity are studied. The method of systemic and structural analysis, as well as the method of logical generalization, are employed in order to study the existing models of organizational maturity, to describe levels of organizational maturity, and finally to develop a set of methodological recommendations for achieving a higher level of organizational project maturity at a given enterprise. The results of the research showed that the core elements of project management system are methodological, organizational, programtechnical, and motivational components. Project management encompasses a wide range of issues connected with organizational structure, project team, communication management, project participants, etc. However, the fundamental basis for developing project management concept within a given enterprise starts with defining its level of organizational maturity. The present paper describes various models of organizational maturity (staged, continuous, petal-shaped and their common types (H. Кеrzner Organizational Maturity Model, Berkeley PM Maturity Model, Organizational Project Management Maturity Model, Portfolio, Program & Project Management Maturity Model. The analysis of available theoretic works showed that the notion “organizational project maturity” refers to the capability of an enterprise to select projects and manage them with the intention of achieving its strategic goals in the most effective way. Importantly, the level of maturity can be improved by means of formalizing the acquired knowledge, regulating project-related activities

  5. Concordancia entre los estadios de maduración esquelética y los estadios de calcificación dental Concordance among skeletal maturation stages and dental calcification stages

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    Gladia Toledo Mayarí

    2010-06-01

    Full Text Available Se realizó una investigación de innovación tecnológica, de corte transversal, con el objetivo de verificar que en los pacientes de ortodoncia se puede prescindir de la radiografía de la mano izquierda en la evaluación del potencial de crecimiento, para lo cual se estudió una muestra de 150 pacientes entre 8 y 16 años, que ingresaron en la Clínica de Ortodoncia de la Facultad de Estomatología de La Habana, entre los años 2004 y 2006. A cada paciente se le realizó una radiografía de la mano izquierda, donde se determinaron los estadios de maduración esquelética a través del método de Grave y Brown y una radiografía panóramica o periapicales de la hemiarcada mandibular izquierda, donde se determinaron los estadios de calcificación del canino y el segundo premolar mandibulares izquierdos, por el método de Demirjian y colaboradores. Se calculó la concordancia entre los métodos evaluados, se encontraron altos coeficientes de concordancia y fue mayor en el sexo masculino y en el canino (Kappa= 0,913. Se concluyó que en la evaluación del potencial de crecimiento que presentan los pacientes de ortodoncia se puede sustituir la radiografía de la mano izquierda por radiografías periapicales del canino y el segundo premolar mandibulares izquierdos, lo cual permite la realización de las radiografías en el propio servicio de estomatología, con los beneficios que ello reporta en cuanto a mejor atención del paciente y ahorro de recursos.A cross-sectional research was conducted related to a technological innovation to verify that in Orthodontics patients it is possible to obviate the left hand X-ray in assessment of the potential growth in 150 patients aged 8 and 16 seen in the Orthodontics Clinic of Stomatology Faculty of La Habana City between 2004 and 2006. In each patient we made an X-ray of left hand determining the skeletal maturation stages by Grave and Brown method and a panoramic or periapical X-ray of the left mandibular

  6. Both brown adipose tissue and skeletal muscle thermogenesis processes are activated during mild to severe cold adaptation in mice.

    Science.gov (United States)

    Bal, Naresh C; Singh, Sushant; Reis, Felipe C G; Maurya, Santosh K; Pani, Sunil; Rowland, Leslie A; Periasamy, Muthu

    2017-10-06

    Thermogenesis is an important homeostatic mechanism essential for survival and normal physiological functions in mammals. Both brown adipose tissue (BAT) ( i.e. uncoupling protein 1 (UCP1)-based) and skeletal muscle ( i.e. sarcolipin (SLN)-based) thermogenesis processes play important roles in temperature homeostasis, but their relative contributions differ from small to large mammals. In this study, we investigated the functional interplay between skeletal muscle- and BAT-based thermogenesis under mild versus severe cold adaptation by employing UCP1 -/- and SLN -/- mice. Interestingly, adaptation of SLN -/- mice to mild cold conditions (16 °C) significantly increased UCP1 expression, suggesting increased reliance on BAT-based thermogenesis. This was also evident from structural alterations in BAT morphology, including mitochondrial architecture, increased expression of electron transport chain proteins, and depletion of fat droplets. Similarly, UCP1 -/- mice adapted to mild cold up-regulated muscle-based thermogenesis, indicated by increases in muscle succinate dehydrogenase activity, SLN expression, mitochondrial content, and neovascularization, compared with WT mice. These results further confirm that SLN-based thermogenesis is a key player in muscle non-shivering thermogenesis (NST) and can compensate for loss of BAT activity. We also present evidence that the increased reliance on BAT-based NST depends on increased autonomic input, as indicated by abundant levels of tyrosine hydroxylase and neuropeptide Y. Our findings demonstrate that both BAT and muscle-based NST are equally recruited during mild and severe cold adaptation and that loss of heat production from one thermogenic pathway leads to increased recruitment of the other, indicating a functional interplay between these two thermogenic processes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Effects of high-fat diet and physical activity on pyruvate dehydrogenase kinase-4 in mouse skeletal muscle

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    Rinnankoski-Tuikka Rita

    2012-06-01

    Full Text Available Abstract Background The expression of PDK4 is elevated by diabetes, fasting and other conditions associated with the switch from the utilization of glucose to fatty acids as an energy source. It is previously shown that peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α, a master regulator of energy metabolism, coactivates in cell lines pyruvate dehydrogenase kinase-4 (PDK4 gene expression via the estrogen-related receptor α (ERRα. We investigated the effects of long-term high-fat diet and physical activity on the expression of PDK4, PGC-1α and ERRα and the amount and function of mitochondria in skeletal muscle. Methods Insulin resistance was induced by a high-fat (HF diet for 19 weeks in C57BL/6 J mice, which were either sedentary or with access to running wheels. The skeletal muscle expression levels of PDK4, PGC-1α and ERRα were measured and the quality and quantity of mitochondrial function was assessed. Results The HF mice were more insulin-resistant than the low-fat (LF -fed mice. Upregulation of PDK4 and ERRα mRNA and protein levels were seen after the HF diet, and when combined with running even more profound effects on the mRNA expression levels were observed. Chronic HF feeding and voluntary running did not have significant effects on PGC-1α mRNA or protein levels. No remarkable difference was found in the amount or function of mitochondria. Conclusions Our results support the view that insulin resistance is not mediated by the decreased qualitative or quantitative properties of mitochondria. Instead, the role of PDK4 should be contemplated as a possible contributor to high-fat diet-induced insulin resistance.

  8. MURC, a muscle-restricted coiled-coil protein, is involved in the regulation of skeletal myogenesis.

    Science.gov (United States)

    Tagawa, Masashi; Ueyama, Tomomi; Ogata, Takehiro; Takehara, Naofumi; Nakajima, Norio; Isodono, Koji; Asada, Satoshi; Takahashi, Tomosaburo; Matsubara, Hiroaki; Oh, Hidemasa

    2008-08-01

    Skeletal myogenesis is a multistep process by which multinucleated mature muscle fibers are formed from undifferentiated, mononucleated myoblasts. However, the molecular mechanisms of skeletal myogenesis have not been fully elucidated. Here, we identified muscle-restricted coiled-coil (MURC) protein as a positive regulator of myogenesis. In skeletal muscle, MURC was localized to the cytoplasm with accumulation in the Z-disc of the sarcomere. In C2C12 myoblasts, MURC expression occurred coincidentally with myogenin expression and preceded sarcomeric myosin expression during differentiation into myotubes. RNA interference (RNAi)-mediated knockdown of MURC impaired differentiation in C2C12 myoblasts, which was accompanied by impaired myogenin expression and ERK activation. Overexpression of MURC in C2C12 myoblasts resulted in the promotion of differentiation with enhanced myogenin expression and ERK activation during differentiation. During injury-induced muscle regeneration, MURC expression increased, and a higher abundance of MURC was observed in immature myofibers compared with mature myofibers. In addition, ERK was activated in regenerating tissue, and ERK activation was detected in MURC-expressing immature myofibers. These findings suggest that MURC is involved in the skeletal myogenesis that results from modulation of myogenin expression and ERK activation. MURC may play pivotal roles in the molecular mechanisms of skeletal myogenic differentiation.

  9. Effects of pO2 on the activation of skeletal muscle ryanodine receptors by NO: a cautionary note.

    Science.gov (United States)

    Cheong, Eunji; Tumbev, Vassil; Stoyanovsky, Detcho; Salama, Guy

    2005-11-01

    Eu et al., reported that O2 dynamically controls the redox state of 6-8 out of 50 thiols per skeletal ryanodine receptor (RyR1) subunit and thereby tunes the response of Ca2+-release channels to authentic nitric oxide (NO) [J.P. Eu, J. Sun, L. Xu, J.S. Stamler, G. Meissner, The skeletal muscle calcium release channel: coupled O2 sensor and NO signaling functions, Cell 102 (2000) 499-509]. A role for O2 was based on the observation that RyR1 can be activated by submicromolar NO at physiological ( approximately 10 mmHg) but not ambient (approximately 150 mmHg) pO2. At ambient pO2, these critical thiols were oxidized but incubation at low pO2 reset the redox state of these thiols, closed RyR1 channels and made these thiols available for nitrosation by low NO concentrations. Eu et al., postulated the existence of a redox/O2sensor that couples channel activity to NO and pO2 and explained that "the nature of the 'redox/O2 sensor' that couples channel activity to intracellular redox chemistry is a mystery". Here, we re-examined the effect of pO2 on RyR1 and find that incubation of RyR1 at low pO2 did not alter channel activity and NO (0.5-50 microM) failed to activate RyR1 despite a wide range of pO2 pre-incubation conditions. We show that low levels of NO do not activate RyR1, do not reverse the inhibition of RyR1 by calmodulin (CaM) even at physiological pO2. Similarly, the pre-incubation of SR vesicles in low pO2 (for 10-80 min) did not inhibit channel activity or sensitization of RyR1 to NO. We discuss the significance of these findings and propose that caution should be taken when considering a role for pO2 and nitrosation by NO as mechanisms that tune RyRs in striated muscles.

  10. Identification of a novel phosphorylation site on TBC1D4 regulated by AMP-activated protein kinase in skeletal muscle

    DEFF Research Database (Denmark)

    Treebak, Jonas Thue; Taylor, Eric B.; Witczak, Carol A.

    2010-01-01

    TBC1D4 (also known as AS160) regulates GLUT4 translocation and glucose uptake in adipocytes and skeletal muscle. Its mode of action involves phosphorylation of Serine (S)/Threonine (T) residues by upstream kinases resulting in inactivation of Rab-GAP activity leading to GLUT4 mobilization...

  11. Swimming-induced exercise promotes hypertrophy and vascularization of fast skeletal muscle fibres and activation of myogenic and angiogenic transcriptional programs in adult zebrafish

    NARCIS (Netherlands)

    Palstra, A.P.; Rovira, M.; Rizo-Roca, D.; Torrella, J.R.; Spaink, H.P.; Planas, J.V.

    2014-01-01

    Background The adult skeletal muscle is a plastic tissue with a remarkable ability to adapt to different levels of activity by altering its excitability, its contractile and metabolic phenotype and its mass. We previously reported on the potential of adult zebrafish as a tractable experimental model

  12. AMP deaminase histochemical activity and immunofluorescent isozyme localization in rat skeletal muscle

    Science.gov (United States)

    Thompson, J. L.; Sabina, R. L.; Ogasawara, N.; Riley, D. A.

    1992-01-01

    The cellular distribution of AMP deaminase (AMPda) isozymes was documented for rat soleus and plantaris muscles, utilizing immunofluorescence microscopy and immunoprecipitation methods. AMPda is a ubiquitous enzyme existing as three distinct isozymes, A, B and C, which were initially purified from skeletal muscle, liver (and kidney), and heart, respectively. AMPda-A is primarily concentrated subsarcolemmally and intermyofibrillarly within muscle cells, while isozymes B and C are concentrated within non-myofiber elements of muscle tissue. AMPda-B is principally associated with connective tissues surrounding neural elements and the muscle spindle capsule, and AMPda-C is predominantly associated with circulatory elements, such as arterial and venous walls, capillary endothelium, and red blood cells. These specific localizations, combined with documented differences in kinetic properties, suggest multiple functional roles for the AMPda isozymes or temporal segregation of similar AMPda functions. Linkage of the AMPda substrate with adenosine production pathways at the AMP level and the localization of isozyme-C in vascular tissue suggest a regulatory role in the microcirculation.

  13. A small-molecule benzimidazole derivative that potently activates AMPK to increase glucose transport in skeletal muscle: comparison with effects of contraction and other AMPK activators.

    Science.gov (United States)

    Lai, Yu-Chiang; Kviklyte, Samanta; Vertommen, Didier; Lantier, Louise; Foretz, Marc; Viollet, Benoît; Hallén, Stefan; Rider, Mark H

    2014-06-15

    AMPK (AMP-activated protein kinase) is an attractive therapeutic drug target for treating metabolic disorders. We studied the effects of an AMPK activator developed by Merck (ex229 from patent application WO2010036613), comparing chemical activation with contraction in intact incubated skeletal muscles. We also compared effects of ex229 with those of the Abbott A769662 compound and AICAR (5-amino-4-imidazolecarboxamide riboside). In rat epitrochlearis muscle, ex229 dose-dependently increased AMPK activity of α1-, α2-, β1- and β2-containing complexes with significant increases in AMPK activity seen at a concentration of 50 μM. At a concentration of 100 μM, AMPK activation was similar to that observed after contraction and importantly led to an ~2-fold increase in glucose uptake. In AMPK α1-/α2-catalytic subunit double-knockout myotubes incubated with ex229, the increases in glucose uptake and ACC (acetyl-CoA carboxylase) phosphorylation seen in control cells were completely abolished, suggesting that the effects of the compound were AMPK-dependent. When muscle glycogen levels were reduced by ~50% after starvation, ex229-induced AMPK activation and glucose uptake were amplified in a wortmannin-independent manner. In L6 myotubes incubated with ex229, fatty acid oxidation was increased. Furthermore, in mouse EDL (extensor digitorum longus) and soleus muscles, ex229 increased both AMPK activity and glucose uptake at least 2-fold. In summary, ex229 efficiently activated skeletal muscle AMPK and elicited metabolic effects in muscle appropriate for treating Type 2 diabetes by stimulating glucose uptake and increasing fatty acid oxidation.

  14. Mesenchymal Stem Cell-Conditioned Medium Modulates Apoptotic and Stress-Related Gene Expression, Ameliorates Maturation and Allows for the Development of Immature Human Oocytes after Artificial Activation

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    Hakimeh Akbari

    2017-12-01

    Full Text Available The aim of the present study was to determine whether mesenchymal stem cell-conditioned medium (MSC-CM modulates apoptotic and stress-related gene expression, and ameliorates maturation and developmental potential of immature human oocytes after artificial activation. A total of 247 surplus immature germinal vesicle (GV oocytes obtained from infertile women were allocated into two in vitro maturation (IVM groups: 1: GV oocytes (n = 116 matured in vitro (fIVM, and 2: GV oocytes (n = 131 that were vitrified, then in vitro matured (vIVM. Also, two maturation media were used: Alpha-minimum essential medium (α-MEM and human umbilical cord-derived MSCs (hUCM. After 36 h of incubation, the IVM oocytes were examined for nuclear maturation. In IVM-matured oocytes, cytoplasmic maturation was evaluated after artificial activation through Ionomycin. Moreover, the quantitative expressions of B-cell CLL/lymphoma 2 (BCL2, BCL2-associated X protein (BAX, superoxide dismutase (SOD, and Heat shock proteins (HSP70 in matured oocytes were assessed by quantitative Real-time polymerase chain reaction (qRT-PCR and compared with fresh and vitrified in vivo matured oocytes, which were used as fIVM and vIVM controls, respectively. The highest maturation rate was found in hUCM in fIVM, and the lowest maturation rate was found using α-MEM in vIVM (85.18% and 71.42%, respectively. The cleavage rate in fIVM was higher than that in vIVM (83.4% vs. 72.0%. In addition, the cleavage rate in α-MEM was lower than that in the hUCM (66.0% vs. 89.4%. Furthermore, the difference between parthenote embryo arrested in 4–8 cells (p < 0.04 and the quality of embryo arrested in 8-cell (p < 0.007 were significant. The developmental stages of parthenote embryos in hUCM versus α-MEM were as follows: 2–4 cell (89.45% vs. 66.00%, respectively, 4–8 cell (44.31% vs. 29.11%, respectively, morula (12.27% vs. 2.63%, respectively, and blastocysts (2.5% vs. 0%, respectively. The messenger

  15. Análise da confiabilidade e da correlação de dois índices de estimativa da maturação esquelética: índice carpal e índice vertebral Reliability and correlation analysis of two skeletal maturation evaluation indexes: hand-wrist index and cervical vertebrae index

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    Melissa Feres Damian

    2006-10-01

    Full Text Available OBJETIVO: o objetivo deste estudo foi avaliar a confiabilidade e a correlação de dois índices de estimativa da maturação esquelética. METODOLOGIA: foi utilizada uma amostra de 210 radiografias carpais e telerradiografias laterais, de arquivo, de pacientes de ambos os gêneros, com idade entre 7 e 18 anos. As radiografias carpais foram utilizadas na determinação do Índice de Maturação Carpal (IMC e as telerradiografias laterais na determinação do Índice de Maturação Vertebral (IMV. Cada grupo de radiografias foi examinado e reexaminado por 4 avaliadores, para analisar a confiabilidade de cada índice, e ainda foi realizada a comparação entre os estágios do IMC e do IMV, para avaliar a correlação entre os índices. RESULTADOS: os resultados demonstraram que não houve diferença estatisticamente significante entre os 4 observadores nas avaliações do IMC e do IMV (pAIM: the aim of this study were to evaluate the reliability and correlation of two different skeletal maturation evaluation indexes. METHODS: two hundred and ten hand-wrist and cephalometric radiographs from files of patients with 7- 18 years old were used. The hand-wrist radiographs were used to determine the skeletal maturation index (SMI and the cephalometric radiographs to determine the cervical vertebrae maturation index (CVMI. Four independent evaluators were asked to examine twice each radiography and to verify the reliability of each index. The stages of SMI and CVMI were compared to evaluate the relationship between them. RESULTS: the results were not statisticaly different among the four evaluators on SMI and CVMI indexes (p<0.00001. The correlation average to SMI was 95% for the first evaluation and 93.5% for the second evaluation. On the CVMI, the correlation average was 84% for the first evaluation and 74% for the second evaluation. The correlation intraoperator did not showed significant difference (p<0.00001 and the average for SMI was 93.5% and for

  16. Hyperthyroidism in Patients with Graves' Ophthalmopathy, and Thyroidal, Skeletal and Eye Muscle Specific Type 2 Deiodinase Enzyme Activities.

    Science.gov (United States)

    Molnár, Ildikó; Szentmiklósi, József A; Somogyiné-Vári, Éva

    2017-09-01

    Graves' ophthalmopathy is characterized by hyperthyroidism, which is associated with higher serum T 3 levels than T 4 due to deiodinase enzymes.The effect of Graves' patient's sera (n=52) with elevated thyroid hormone and TSH receptor or thyroid peroxidase antibody (anti-TPO) levels was investigated on thyroidal, skeletal and eye muscle type 2 deiodinase enzyme (DII) activities. DII activities were measured with 125 I-T 4 substrate, while thyroid hormone and antibody levels with immunoassays.In Graves' ophthalmopathy, sera with elevated FT 4 or FT 3 levels reduced DII activites remarkably in all tissue fractions. Thyroidal DII activities were lower than those using eye muscle fraction (0.6±0.22 vs 1.14±0.43 pmol/mg/min, PEffect of sera with increased FT 3 levels demonstrated also reduced DII activities in patients with Graves' ophthalmopathy after methimazole therapy compared to those who had no ophthalmopathy (2.88±2 vs 20.42±11.82 pmol/mg/min, PHyperthyroid sera with TSH receptor antibodies resulted in increased DII activities, while sera with anti-TPO antibodies were connected to lower DII activities in Graves' ophthalmopathy.In summary, the actions of hyperthyroid sera derived from patients with Graves' disease were tested on tissue-specific DII activities. Elevated FT 4 level-induced DII inactivation is present in Graves' ophthalmopathy, which seems to be also present at the beginning of methimazole therapy. Stimulating TSH receptor antibiodies increased DII activities via their nongenomic effects using sera of hyperthyroid Graves' ophthalmopathy, but anti-TPO antibodies could influence DII activities via altering FT 4 levels. © Georg Thieme Verlag KG Stuttgart · New York.

  17. [From gene to disease; achondroplasia and other skeletal dysplasias due to an activating mutation in the fibroblast growth factor

    NARCIS (Netherlands)

    Ravenswaaij-Arts, C.M.A. van; Losekoot, M.

    2001-01-01

    Achondroplasia, the most common and best known skeletal dysplasia, is inherited in an autosomal dominant fashion. Like a number of other skeletal dysplasias, among which hypochondroplasia and thanatophoric dysplasia, achondroplasia is caused by mutations in the fibroblast growth factor receptor 3

  18. When phosphorylated at Thr148, the β2-subunit of AMP-activated kinase does not associate with glycogen in skeletal muscle.

    Science.gov (United States)

    Xu, Hongyang; Frankenberg, Noni T; Lamb, Graham D; Gooley, Paul R; Stapleton, David I; Murphy, Robyn M

    2016-07-01

    The 5'-AMP-activated protein kinase (AMPK), a heterotrimeric complex that functions as an intracellular fuel sensor that affects metabolism, is activated in skeletal muscle in response to exercise and utilization of stored energy. The diffusibility properties of α- and β-AMPK were examined in isolated skeletal muscle fiber segments dissected from rat fast-twitch extensor digitorum longus and oxidative soleus muscles from which the surface membranes were removed by mechanical dissection. After the muscle segments were washed for 1 and 10 min, ∼60% and 75%, respectively, of the total AMPK pools were found in the diffusible fraction. After in vitro stimulation of the muscle, which resulted in an ∼80% decline in maximal force, 20% of the diffusible pool became bound in the fiber. This bound pool was not associated with glycogen, as determined by addition of a wash step containing amylase. Stimulation of extensor digitorum longus muscles resulted in 28% glycogen utilization and a 40% increase in phosphorylation of the downstream AMPK target acetyl carboxylase-CoA. This, however, had no effect on the proportion of total β2-AMPK that was phosphorylated in whole muscle homogenates measured by immunoprecipitation. These findings suggest that, in rat skeletal muscle, β2-AMPK is not associated with glycogen and that activation of AMPK by muscle contraction does not dephosphorylate β2-AMPK. These findings question the physiological relevance of the carbohydrate-binding function of β2-AMPK in skeletal muscle. Copyright © 2016 the American Physiological Society.

  19. Lung injury-dependent oxidative status and chymotrypsin-like activity of skeletal muscles in hamsters with experimental emphysema.

    Science.gov (United States)

    Tonon, Jair; Cecchini, Alessandra Lourenço; Brunnquell, Cláudia Roberta; Bernardes, Sara Santos; Cecchini, Rubens; Guarnier, Flávia Alessandra

    2013-01-23

    Peripheral skeletal muscle is altered in patients suffering from emphysema and chronic obstructive pulmonary disease (COPD). Oxidative stress have been demonstrated to participate on skeletal muscle loss of several states, including disuse atrophy, mechanical ventilation, and chronic diseases. No evidences have demonstrated the occurance in a severity manner. We evaluated body weight, muscle loss, oxidative stress, and chymotrypsin-like proteolytic activity in the gastrocnemius muscle of emphysemic hamsters. The experimental animals had 2 different severities of lung damage from experimental emphysema induced by 20 mg/mL (E20) and 40 mg/mL (E40) papain. The severity of emphysema increased significantly in E20 (60.52 ± 2.8, p < 0.05) and E40 (52.27 ± 4.7; crossed the alveolar intercepts) groups. As compared to the control group, there was a reduction on body (171.6 ± 15.9 g) and muscle weight (251.87 ± 24.87 mg) in the E20 group (157.5 ± 10.3 mg and 230.12 ± 23.52 mg, for body and muscle weight, respectively), which was accentuated in the E40 group (137.4 ± 7.2 g and 197.87 ± 10.49 mg, for body and muscle weight, respectively). Additionally, the thiobarbituric acid reactive substances (TBARS), tert-butyl hydroperoxide-initiated chemiluminescence (CL), carbonylated proteins, and chymotrypsin-like proteolytic activity were elevated in the E40 group as compared to the E20 group (p < 0.05 for all comparisons). The severity of emphysema significantly correlated with the progressive increase in CL (r = -0.95), TBARS (r = -0.98), carbonyl proteins (r = -0.99), and chymotrypsin-like proteolytic activity (r = -0.90). Furthermore, augmentation of proteolytic activity correlated significantly with CL (r = 0.97), TBARS (r = 0.96), and carbonyl proteins (r = 0.91). Taken together, the results of the present study suggest that muscle atrophy observed in this model of emphysema is mediated by increased muscle chymotrypsin-like activity, with possible involvement of

  20. The Second-Generation Maturation Inhibitor GSK3532795 Maintains Potent Activity Toward HIV Protease Inhibitor-Resistant Clinical Isolates.

    Science.gov (United States)

    Ray, Neelanjana; Li, Tianbo; Lin, Zeyu; Protack, Tricia; van Ham, Petronella Maria; Hwang, Carey; Krystal, Mark; Nijhuis, Monique; Lataillade, Max; Dicker, Ira

    2017-05-01

    Protease inhibitor (PI)-resistant HIV-1 isolates with primary substitutions in protease (PR) and secondary substitutions in Gag could potentially exhibit cross-resistance to maturation inhibitors. We evaluated the second-generation maturation inhibitor, GSK3532795, for activity toward clinical isolates with genotypic and phenotypic characteristics associated with PI resistance (longitudinal). Longitudinal clinical isolates from 15 PI-treated patients and 7 highly PI-resistant (nonlongitudinal) viruses containing major and minor PI resistance-associated mutations were evaluated for GSK3532795 sensitivity. Phenotypic sensitivity was determined using the PhenoSense Gag/PR assay (Monogram Biosciences) or in-house single- and multiple-cycle assays. Changes from baseline [CFB; ratio of post- to pre-treatment FC-IC50 (fold-change in IC50 versus wild-type virus)] Monogram (11 patients)] and 1.5 (1.0-2.2) [single-cycle (4 patients)]. The 2 post-PI treatment samples showing GSK3532795 CFB >3 (Monogram) were retested using single- and multiple-cycle assays. Neither sample had meaningful sensitivity changes in the multiple-cycle assay. Gag changes were not associated with an increased GSK3532795 CFB. GSK3532795 maintained antiviral activity against PI-resistant isolates with emergent PR and/or Gag mutations. This finding supports continued development of GSK3532795 in treatment-experienced patients with or without previous PI therapy.

  1. The Second-Generation Maturation Inhibitor GSK3532795 Maintains Potent Activity Toward HIV Protease Inhibitor–Resistant Clinical Isolates

    Science.gov (United States)

    Ray, Neelanjana; Li, Tianbo; Lin, Zeyu; Protack, Tricia; van Ham, Petronella Maria; Hwang, Carey; Krystal, Mark; Nijhuis, Monique; Lataillade, Max

    2017-01-01

    Background: Protease inhibitor (PI)-resistant HIV-1 isolates with primary substitutions in protease (PR) and secondary substitutions in Gag could potentially exhibit cross-resistance to maturation inhibitors. We evaluated the second-generation maturation inhibitor, GSK3532795, for activity toward clinical isolates with genotypic and phenotypic characteristics associated with PI resistance (longitudinal). Methods: Longitudinal clinical isolates from 15 PI-treated patients and 7 highly PI-resistant (nonlongitudinal) viruses containing major and minor PI resistance-associated mutations were evaluated for GSK3532795 sensitivity. Phenotypic sensitivity was determined using the PhenoSense Gag/PR assay (Monogram Biosciences) or in-house single- and multiple-cycle assays. Changes from baseline [CFB; ratio of post- to pre-treatment FC-IC50 (fold-change in IC50 versus wild-type virus)] Monogram (11 patients)] and 1.5 (1.0–2.2) [single-cycle (4 patients)]. The 2 post-PI treatment samples showing GSK3532795 CFB >3 (Monogram) were retested using single- and multiple-cycle assays. Neither sample had meaningful sensitivity changes in the multiple-cycle assay. Gag changes were not associated with an increased GSK3532795 CFB. Conclusions: GSK3532795 maintained antiviral activity against PI-resistant isolates with emergent PR and/or Gag mutations. This finding supports continued development of GSK3532795 in treatment-experienced patients with or without previous PI therapy. PMID:28234686

  2. The Influence of 2-Year Changes in Physical Activity, Maturation, and Nutrition on Adiposity in Adolescent Youth.

    Directory of Open Access Journals (Sweden)

    Javier Benítez-Porres

    Full Text Available The aim of this longitudinal study was to explore temporal patterns of physical activity (PA and adiposity in Spanish adolescents. Eighty healthy adolescents were followed over a 2-year period (42 girls and 38 boys. A PA score was estimated using the Physical Activity Questionnaire for Adolescents (PAQ-A. Adiposity was assessed by anthropometric measurements; body mass index (BMI and fat mass percent (FMP were calculated using standard equations. Sexual maturity was estimated by percentage of predicted adult stature. Dietary intake was assessed by a self-administered food-frequency questionnaire. Three assessments were performed: September 2011 (S1, 2012 (S2, and 2013 (S3. A repeated-measures ANOVA was conducted to examine temporal changes in PA and FMP and sex change in maturation categories (two factor mixed-design, 2x2x3. A stepwise linear regression was conducted in order to estimate the predictors of FMP change. Significant changes for FMP were found between S1, S2, and S3 (23.41±8.24 vs. 21.89±7.82 vs. 22.05±8.06, p<0.05; respectively; a significant interaction of FMP with sex was observed (F = 4.387, p<0.05 for S2-S3, but not for maturation. PA at S2 was significantly higher than S3 (2.58±0.72 vs. 2.29±0.73, p<0.001. An interaction between PA change and sex was statically significant (F = 4.889, p<0.05 for S2-S3. A reduction in PA was observed after the S2 period without changes in adiposity. In contrast, a significant reduction in FMP was seen between S1 and S2, while PA did not significantly change. There were no significant differences for nutritional variables between S1 and S3, and nutrition was not a determinant of the changes in PA or FMP. Our results suggest that body composition changes observed during adolescence are not driven by changes in PA. Moreover, the interaction analysis suggests that PA behavior is affected by sex, but is not modified by maturation.

  3. A molecular chaperone activity of CCS restores the maturation of SOD1 fALS mutants.

    Science.gov (United States)

    Luchinat, Enrico; Barbieri, Letizia; Banci, Lucia

    2017-12-12

    Superoxide dismutase 1 (SOD1) is an important metalloprotein for cellular oxidative stress defence, that is mutated in familiar variants of Amyotrophic Lateral Sclerosis (fALS). Some mutations destabilize the apo protein, leading to the formation of misfolded, toxic species. The Copper Chaperone for SOD1 (CCS) transiently interacts with SOD1 and promotes its correct maturation by transferring copper and catalyzing disulfide bond formation. By in vitro and in-cell NMR, we investigated the role of the SOD-like domain of CCS (CCS-D2). We showed that CCS-D2 forms a stable complex with zinc-bound SOD1 in human cells, that has a twofold stabilizing effect: it both prevents the accumulation of unstructured mutant SOD1 and promotes zinc binding. We further showed that CCS-D2 interacts with apo-SOD1 in vitro, suggesting that in cells CCS stabilizes mutant apo-SOD1 prior to zinc binding. Such molecular chaperone function of CCS-D2 is novel and its implications in SOD-linked fALS deserve further investigation.

  4. The effects of low frequency electrical stimulation on satellite cell activity in rat skeletal muscle during hindlimb suspension

    Directory of Open Access Journals (Sweden)

    Zhang Hong-Yu

    2010-11-01

    Full Text Available Abstract Background The ability of skeletal muscle to grow and regenerate is dependent on resident stem cells called satellite cells. It has been shown that chronic hindlimb unloading downregulates the satellite cell activity. This study investigated the role of low-frequency electrical stimulation on satellite cell activity during a 28 d hindlimb suspension in rats. Results Mechanical unloading resulted in a 44% reduction in the myofiber cross-sectional area as well as a 29% and 34% reduction in the number of myonuclei and myonuclear domains, respectively, in the soleus muscles (P vs the weight-bearing control. The number of quiescent (M-cadherin+, proliferating (BrdU+ and myoD+, and differentiated (myogenin+ satellite cells was also reduced by 48-57% compared to the weight-bearing animals (P P Conclusion This study shows that electrical stimulation partially attenuated the decrease in muscle size and satellite cells during hindlimb unloading. The causal relationship between satellite cell activation and electrical stimulation remain to be established.

  5. Regulation of skeletal muscle mitochondrial activity by thyroid hormones: focus on "old" triiodothyronine and the "emerging" 3,5-diiodothyronine".

    Directory of Open Access Journals (Sweden)

    Assunta eLombardi

    2015-08-01

    Full Text Available 3,5,3'-triiodo-L-thyronine (T3 plays a crucial role in regulating metabolic rate and fuel oxidation; however, the mechanisms by which it affects whole-body energy metabolism are still not completely understood. Skeletal muscle (SKM plays a relevant role in energy metabolism and responds to thyroid state by remodeling the metabolic characteristics and cytoarchitecture of myocytes. These processes are coordinated with changes in mitochondrial content, bioenergetics, substrate oxidation rate, and oxidative phosphorylation efficiency. Recent data indicate that emerging iodothyronines have biological activity. Among these, 3,5-diiodo-L-thyronine (T2 affects energy metabolism, SKM substrate utilization, and mitochondrial functionality. The effects it exerts on SKM mitochondria involve more aspects of mitochondrial bioenergetics; among these, respiratory chain activity, mitochondrial thermogenesis, and lipid-handling are stimulated rapidly. This minireview focuses on signaling and biochemical pathways activated by T3 and T2 in SKM that influence the above processes. These novel aspects of thyroid physiology could reveal new perspectives for understanding the involvement of SKM mitochondria in hypo- and hyperthyroidism.

  6. Adaptive responses of mouse skeletal muscle to contractile activity: The effect of age.

    Science.gov (United States)

    Vasilaki, A; McArdle, F; Iwanejko, L M; McArdle, A

    2006-11-01

    This study has characterised the time course of two major transcriptional adaptive responses to exercise (changes in antioxidant defence enzyme activity and heat shock protein (HSP) content) in muscles of adult and old male mice following isometric contractions and has examined the mechanisms involved in the age-related reduction in transcription factor activation. Muscles of B6XSJL mice were subjected to isometric contractions and analysed for antioxidant defence enzyme activities, heat shock protein content and transcription factor DNA binding activity. Data demonstrated a significant increase in superoxide dismutase (SOD) and catalase activity and HSP content of muscles of adult mice following contractile activity which was associated with increased activation of the transcription factors, nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1) and heat shock factor (HSF) following contractions. Significant increases in SOD and catalase activity and heat shock cognate (HSC70) content were seen in quiescent muscles of old mice. The increase in antioxidant defence enzyme activity following contractile activity seen in muscles of adult mice was not seen in muscles of old mice and this was associated with a failure to fully activate NF-kappaB and AP-1 following contractions. In contrast, although the production of HSPs was also reduced in muscles of old mice following contractile activity compared with muscles of adult mice following contractions, this was not due to a gross reduction in the DNA binding activity of HSF.

  7. Effects of high-intensity swimming training on GLUT-4 and glucose transport activity in rat skeletal muscle.

    Science.gov (United States)

    Terada, S; Yokozeki, T; Kawanaka, K; Ogawa, K; Higuchi, M; Ezaki, O; Tabata, I

    2001-06-01

    This study was performed to assess the effects of short-term, extremely high-intensity intermittent exercise training on the GLUT-4 content of rat skeletal muscle. Three- to four-week-old male Sprague-Dawley rats with an initial body weight ranging from 45 to 55 g were used for this study. These rats were randomly assigned to an 8-day period of high-intensity intermittent exercise training (HIT), relatively high-intensity intermittent prolonged exercise training (RHT), or low-intensity prolonged exercise training (LIT). Age-matched sedentary rats were used as a control. In the HIT group, the rats repeated fourteen 20-s swimming bouts with a weight equivalent to 14, 15, and 16% of body weight for the first 2, the next 4, and the last 2 days, respectively. Between exercise bouts, a 10-s pause was allowed. RHT consisted of five 17-min swimming bouts with a 3-min rest between bouts. During the first bout, the rat swam without weight, whereas during the following four bouts, the rat was attached to a weight equivalent to 4 and 5% of its body weight for the first 5 days and the following 3 days, respectively. Rats in the LIT group swam 6 h/day for 8 days in two 3-h bouts separated by 45 min of rest. In the first experiment, the HIT, LIT, and control rats were compared. GLUT-4 content in the epitrochlearis muscle in the HIT and LIT groups after training was significantly higher than that in the control rats by 83 and 91%, respectively. Furthermore, glucose transport activity, stimulated maximally by both insulin (2 mU/ml) (HIT: 48%, LIT: 75%) and contractions (25 10-s tetani) (HIT: 55%, LIT: 69%), was higher in the training groups than in the control rats. However, no significant differences in GLUT-4 content or in maximal glucose transport activity in response to both insulin and contractions were observed between the two training groups. The second experiment demonstrated that GLUT-4 content after HIT did not differ from that after RHT (66% higher in trained rats than

  8. Sarcomere length-dependence of activity-dependent twitch potentiation in mouse skeletal muscle

    Directory of Open Access Journals (Sweden)

    MacIntosh Brian R

    2002-12-01

    Full Text Available Abstract Background It has been reported that potentiation of a skeletal muscle twitch response is proportional to muscle length with a negative slope during staircase, and a positive slope during posttetanic potentiation. This study was done to directly compare staircase and posttetanic responses with measurement of sarcomere length to compare their length-dependence. Methods Mouse extensor digitorum longus (EDL muscles were dissected to small bundles of fibers, which permit measurement of sarcomere length (SL, by laser diffraction. In vitro fixed-end contractions of EDL fiber bundles were elicited at 22°C and 35°C at sarcomere lengths ranging from 2.35 μm to 3.85 μm. Twitch contractions were assessed before and after 1.5 s of 75 Hz stimulation at 22°C or during 10 s of 10 Hz stimulation at 22°C or 35°C. Results Staircase potentiation was greater at 35°C than 22°C, and the relative magnitude of the twitch contraction (Pt*/Pt was proportional to sarcomere length with a negative slope, over the range 2.3 μm – 3.7 μm. Linear regression yielded the following: Pt*/Pt = -0.59·SL+3.27 (r2 = 0.74; Pt*/Pt = -0.39·SL+2.34 (r2 = 0.48; and Pt*/Pt = -0.50·SL+2.45 (r2 = 0.80 for staircase at 35°C, and 22°C and posttetanic response respectively. Posttetanic depression rather than potentiation was present at long SL. This indicates that there may be two processes operating in these muscles to modulate the force: one that enhances and a second that depresses the force. Either or both of these processes may have a length-dependence of its mechanism. Conclusion There is no evidence that posttetanic potentiation is fundamentally different from staircase in these muscles.

  9. Physical activity opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension.

    Science.gov (United States)

    Nyberg, M; Mortensen, S P; Hellsten, Y

    2013-03-01

    Endothelin-1 has potent constrictor and proliferative activity in vascular smooth muscle, and essential hypertension and aging are associated with increased endothelin-1-mediated vasoconstrictor tone. The aim of this study was to investigate the effect of physical activity, hypertension and age on endothelin-1 levels in plasma and skeletal muscle and endothelin receptors in skeletal muscle in human subjects. In study 1, normotensive (46 ± 1 years, n = 11) and hypertensive (47 ± 1 years, n = 10) subjects were studied before and after 8 weeks of aerobic exercise training. In study 2, young (23 ± 1 years, n = 8), older lifelong sedentary (66 ± 2 years, n = 8) and older lifelong endurance-trained (62 ± 2 years, n = 8) subjects were studied in a cross-sectional design. Skeletal muscle and plasma endothelin-1 levels were increased with age and plasma endothelin-1 levels were higher in hypertensive than normotensive individuals. Eight weeks of exercise training normalized plasma endothelin-1 levels in the hypertensive subjects and increased the protein expression of the ET(A) receptor in skeletal muscle of normotensive subjects. Similarly, individuals that had performed lifelong physical activity had similar plasma and muscle endothelin-1 levels as the young controls and had higher ET(A) receptor levels. Our findings suggest that aerobic exercise training opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension. This effect may explain some of the beneficial effects of training on the cardiovascular system in older and hypertensive subjects. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

  10. GSNOR Deficiency Enhances In Situ Skeletal Muscle Strength, Fatigue Resistance, and RyR1 S-Nitrosylation Without Impacting Mitochondrial Content and Activity

    Science.gov (United States)

    Moon, Younghye; Cao, Yenong; Zhu, Jingjing; Xu, Yuanyuan; Balkan, Wayne; Buys, Emmanuel S.; Diaz, Francisca; Kerrick, W. Glenn; Hare, Joshua M.

    2017-01-01

    Abstract Aim: Nitric oxide (NO) plays important, but incompletely defined roles in skeletal muscle. NO exerts its regulatory effects partly though S-nitrosylation, which is balanced by denitrosylation by enzymes such as S-nitrosoglutathione reductase (GSNOR), whose functions in skeletal muscle remain to be fully deciphered. Results: GSNOR null (GSNOR−/−) tibialis anterior (TA) muscles showed normal growth and were stronger and more fatigue resistant than controls in situ. However, GSNOR−/− lumbrical muscles showed normal contractility and Ca2+ handling in vitro, suggesting important differences in GSNOR function between muscles or between in vitro and in situ environments. GSNOR−/− TA muscles exhibited normal mitochondrial content, and capillary densities, but reduced type IIA fiber content. GSNOR inhibition did not impact mitochondrial respiratory complex I, III, or IV activities. These findings argue that enhanced GSNOR−/− TA contractility is not driven by changes in mitochondrial content or activity, fiber type, or blood vessel density. However, loss of GSNOR led to RyR1 hypernitrosylation, which is believed to increase muscle force output under physiological conditions. cGMP synthesis by soluble guanylate cyclase (sGC) was decreased in resting GSNOR−/− muscle and was more responsive to agonist (DETANO, BAY 41, and BAY 58) stimulation, suggesting that GSNOR modulates cGMP production in skeletal muscle. Innovation: GSNOR may act as a “brake” on skeletal muscle contractile performance under physiological conditions by modulating nitrosylation/denitrosylation balance. Conclusions: GSNOR may play important roles in skeletal muscle contractility, RyR1 S-nitrosylation, fiber type specification, and sGC activity. Antioxid. Redox Signal. 26, 165–181. PMID:27412893

  11. People Capability Maturity Model. SM.

    Science.gov (United States)

    1995-09-01

    tailored so it consumes less time and resources than a traditional software process assessment or CMU/SEI-95-MM-02 People Capability Maturity Model...improved reputation or customer loyalty. CMU/SEI-95-MM-02 People Capability Maturity Model ■ L5-17 Coaching Level 5: Optimizing Activity 1...Maturity Model CMU/SEI-95-MM-62 Carnegie-Mellon University Software Engineering Institute DTIC ELECTE OCT 2 7 1995 People Capability Maturity

  12. Kinase activity determination of specific AMPK complexes/heterotrimers in the skeletal muscle

    DEFF Research Database (Denmark)

    Birk, Jesper Bratz; Wojtaszewski, Jørgen

    2018-01-01

    Measuring the kinase activity of the 5'-AMP-activated protein kinase (AMPK) is an essential part of understanding the regulation of this metabolic master switch. The AMPK heterotrimer can exist in 12 different constellations with potentially diverse activation patterns. It is therefore important ...

  13. ROS detoxification and proinflammatory cytokines are linked by p38 MAPK signaling in a model of mature astrocyte activation.

    Directory of Open Access Journals (Sweden)

    Adrian Nahirnyj

    Full Text Available Astrocytes are the most abundant glial cell in the retinal nerve fiber layer (NFL and optic nerve head (ONH, and perform essential roles in maintaining retinal ganglion cell (RGC detoxification and homeostasis. Mature astrocytes are relatively quiescent, but rapidly undergo a phenotypic switch in response to insult, characterized by upregulation of intermediate filament proteins, loss of glutamate buffering, secretion of pro-inflammatory cytokines, and increased antioxidant production. These changes result in both positive and negative influences on RGCs. However, the mechanism regulating these responses is still unclear, and pharmacologic strategies to modulate select aspects of this switch have not been thoroughly explored. Here we describe a system for rapid culture of mature astrocytes from the adult rat retina that remain relatively quiescent, but respond robustly when challenged with oxidative damage, a key pathogenic stress associated with inner retinal injury. When primary astrocytes were exposed to reactive oxygen species (ROS we consistently observed characteristic changes in activation markers, along with increased expression of detoxifying genes, and secretion of proinflammatory cytokines. This in vitro model was then used for a pilot chemical screen to target specific aspects of this switch. Increased activity of p38α and β Mitogen Activated Protein Kinases (MAPKs were identified as a necessary signal regulating expression of MnSOD, and heme oxygenase 1 (HO-1, with consequent changes in ROS-mediated injury. Additionally, multiplex cytokine profiling detected p38 MAPK-dependent secretion of IL-6, MCP-1, and MIP-2α, which are proinflammatory signals recently implicated in damage to the inner retina. These data provide a mechanism to link increased oxidative stress to proinflammatory signaling by astrocytes, and establish this assay as a useful model to further dissect factors regulating the reactive switch.

  14. Analysis of STAT1 activation by six FGFR3 mutants associated with skeletal dysplasia undermines dominant role of STAT1 in FGFR3 signaling in cartilage.

    Directory of Open Access Journals (Sweden)

    Pavel Krejci

    Full Text Available Activating mutations in FGFR3 tyrosine kinase cause several forms of human skeletal dysplasia. Although the mechanisms of FGFR3 action in cartilage are not completely understood, it is believed that the STAT1 transcription factor plays a central role in pathogenic FGFR3 signaling. Here, we analyzed STAT1 activation by the N540K, G380R, R248C, Y373C, K650M and K650E-FGFR3 mutants associated with skeletal dysplasias. In a cell-free kinase assay, only K650M and K650E-FGFR3 caused activatory STAT1(Y701 phosphorylation. Similarly, in RCS chondrocytes, HeLa, and 293T cellular environments, only K650M and K650E-FGFR3 caused strong STAT1 activation. Other FGFR3 mutants caused weak (HeLa or no activation (293T and RCS. This contrasted with ERK MAP kinase activation, which was strongly induced by all six mutants and correlated with the inhibition of proliferation in RCS chondrocytes. Thus the ability to activate STAT1 appears restricted to the K650M and K650E-FGFR3 mutants, which however account for only a small minority of the FGFR3-related skeletal dysplasia cases. Other pathways such as ERK should therefore be considered as central to pathological FGFR3 signaling in cartilage.

  15. Behavioral and Locomotor Measurements Using an Open Field Activity Monitoring System for Skeletal Muscle Diseases

    OpenAIRE

    Tatem, Kathleen S.; Quinn, James L.; Phadke, Aditi; Yu, Qing; Gordish-Dressman, Heather; Nagaraju, Kanneboyina

    2014-01-01

    The open field activity monitoring system comprehensively assesses locomotor and behavioral activity levels of mice. It is a useful tool for assessing locomotive impairment in animal models of neuromuscular disease and efficacy of therapeutic drugs that may improve locomotion and/or muscle function. The open field activity measurement provides a different measure than muscle strength, which is commonly assessed by grip strength measurements. It can also show how drugs may affect other body sy...

  16. Health-related quality of life of Portuguese children and adolescents according to their biological maturation and volume of physical activity.

    Science.gov (United States)

    Garcia, Catarina; Teles, Júlia; Barrigas, Carlos; Fragoso, Isabel

    2018-06-01

    The purpose of this study was to analyze the relationship between biological maturation and health-related quality of life (HRQoL) in Portuguese children and adolescents of both sexes when the effect of chronological age (CA) and volume of physical activity (VPA) were removed. HRQoL, biological maturation, CA, and VPA were assessed in 750 children and adolescents, 11-17 years old, from 3 schools in Lisbon, Portugal. The KIDSCREEN-52 was used to assess HRQoL. Maturity indicator was bone age (BA), using Tanner-Whitehouse III method (TW3). The participants were classified into three different maturity categories: late, on time, and early maturers. VPA was assessed by questionnaire (RAPIL II). An analysis of covariance (ANCOVA), using the CA and the VPA as covariates was completed. The level of significance was set at p ≤ 0.05. Analysis of covariance suggested an influence of biological maturation in physical well-being dimension in both sexes, with early-maturing girls and boys having worst perception. Maturity groups were also influent in moods and emotions for girls. CA seems to be particularly important in self-perception and parent relation and home life for girls and in school environment for boys. Biological maturation and CA have relevant impact on some HRQoL dimensions. These variables, due to their nature and effect should be considered particularly when working with specific domains of HRQoL as physical well-being in both sexes, moods and emotions and self-perception and parent relation and home life for girls and in school environment for boys.

  17. Contraction-mediated glycogenolysis in mouse skeletal muscle lacking creatine kinase: the role of phosphorylase b activation.

    NARCIS (Netherlands)

    Katz, A.; Andersson, D.C.; Yu, J.; Norman, B.; Sandstrom, M.E.; Wieringa, B.; Westerblad, H.

    2003-01-01

    Skeletal muscle that is deficient in creatine kinase (CK-/-) exhibits accelerated glycogenolysis during contraction. Understanding this phenomenon could provide insight into the control of glycogenolysis during contraction. Therefore, glycogen breakdown was investigated in isolated extensor

  18. Benefits of sport activities for people with cerebral pa/sy in adolescence and maturity age

    OpenAIRE

    Jamrichová, Jana

    2012-01-01

    Possibilities and benefits of sport activities for people with cerebral palsy in Czech republic The aim of this work is to determine what are the possibilities and benefits of sports for people with cerebral palsy in the Czech Republic. To detect what kinds of different sports for people with disabilities are offered, as well as to find out various sports clubs, associations and organizations that allow these activities. Another aim of my work is to describe the history of sports for people w...

  19. Artificial activation of mature unfertilized eggs in the malaria vector mosquito, Anopheles stephensi (Diptera, Culicidae).

    Science.gov (United States)

    Yamamoto, Daisuke S; Hatakeyama, Masatsugu; Matsuoka, Hiroyuki

    2013-08-01

    In the past decade, many transgenic lines of mosquitoes have been generated and analyzed, whereas the maintenance of a large number of transgenic lines requires a great deal of effort and cost. In vitro fertilization by an injection of cryopreserved sperm into eggs has been proven to be effective for the maintenance of strains in mammals. The technique of artificial egg activation is a prerequisite for the establishment of in vitro fertilization by sperm injection. We demonstrated that artificial egg activation is feasible in the malaria vector mosquito, Anopheles stephensi (Diptera, Culicidae). Nearly 100% of eggs dissected from virgin females immersed in distilled water darkened, similar to normally oviposited fertilized eggs. It was revealed by the cytological examination of chromosomes that meiotic arrest was relieved in these eggs approximately 20 min after incubation in water. Biochemical examinations revealed that MAPK (mitogen-activated protein kinase)/ERK (extracellular signal-regulated protein kinase) and MEK (MAPK/ERK kinase) were dephosphorylated similar to that in fertilized eggs. These results indicate that dissected unfertilized eggs were activated in distilled water and started development. Injection of distilled water into body cavity of the virgin blood-fed females also induced activation of a portion of eggs in the ovaries. The technique of artificial egg activation is expected to contribute to the success of in vitro fertilization in A. stephensi.

  20. Myostatin-deficiency in mice increases global gene expression at the Dlk1-Dio3 locus in the skeletal muscle.

    Science.gov (United States)

    Hitachi, Keisuke; Tsuchida, Kunihiro

    2017-01-24

    Myostatin, a member of the transforming growth factor-beta superfamily, is a negative regulator of skeletal muscle growth and development. Myostatin inhibition leads to increased skeletal muscle mass in mammals; hence, myostatin is considered a potential therapeutic target for skeletal muscle wasting. However, downstream molecules of myostatin in the skeletal muscle have not been fully elucidated. Here, we identified the Dlk1-Dio3 locus at the mouse chromosome 12qF1, also called as the callipyge locus in sheep, as a novel downstream target of myostatin. In skeletal muscle of myostatin knockout mice, the expression of mature miRNAs at the Dlk1-Dio3 locus was significantly increased. The increased miRNA levels are caused by the transcriptional activation of the Dlk1-Dio3 locus, because a significant increase in the primary miRNA transcript was observed in myostatin knockout mice. In addition, we found increased expression of coding and non-coding genes (Dlk1, Gtl2, Rtl1/Rtl1as, and Rian) at the Dlk1-Dio3 locus in myostatin-deficient skeletal muscle. Moreover, epigenetic changes, associated with the regulation of the Dlk1-Dio3 locus, were observed in myostatin knockout mice. Taken together, this is the first report demonstrating the role of myostatin in regulating the Dlk1-Dio3 (the callipyge) locus in the skeletal muscle.

  1. Anticipation of peer evaluation in anxious adolescents: divergence in neural activation and maturation.

    Science.gov (United States)

    Spielberg, Jeffrey M; Jarcho, Johanna M; Dahl, Ronald E; Pine, Daniel S; Ernst, Monique; Nelson, Eric E

    2015-08-01

    Adolescence is the time of peak onset for many anxiety disorders, particularly Social Anxiety Disorder. Research using simulated social interactions consistently finds differential activation in several brain regions in anxious (vs non-anxious) youth, including amygdala, striatum and medial prefrontal cortex. However, few studies examined the anticipation of peer interactions, a key component in the etiology and maintenance of anxiety disorders. Youth completed the Chatroom Task while undergoing functional magnetic resonance imaging. Patterns of neural activation were assessed in anxious and non-anxious youth as they were cued to anticipate social feedback from peers. Anxious participants evidenced greater amygdala activation and rostral anterior cingulate (rACC)↔amygdala coupling than non-anxious participants during anticipation of feedback from peers they had previously rejected; anxious participants also evidenced less nucleus accumbens activation during anticipation of feedback from selected peers. Finally, anxiety interacted with age in rACC: in anxious participants, age was positively associated with activation to anticipated feedback from rejected peers and negatively for selected peers, whereas the opposite pattern emerged for non-anxious youth. Overall, anxious youth showed greater reactivity in anticipation of feedback from rejected peers and thus may ascribe greater salience to these potential interactions and increase the likelihood of avoidance behavior. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  2. Behavioral and locomotor measurements using an open field activity monitoring system for skeletal muscle diseases.

    Science.gov (United States)

    Tatem, Kathleen S; Quinn, James L; Phadke, Aditi; Yu, Qing; Gordish-Dressman, Heather; Nagaraju, Kanneboyina

    2014-09-29

    The open field activity monitoring system comprehensively assesses locomotor and behavioral activity levels of mice. It is a useful tool for assessing locomotive impairment in animal models of neuromuscular disease and efficacy of therapeutic drugs that may improve locomotion and/or muscle function. The open field activity measurement provides a different measure than muscle strength, which is commonly assessed by grip strength measurements. It can also show how drugs may affect other body systems as well when used with additional outcome measures. In addition, measures such as total distance traveled mirror the 6 min walk test, a clinical trial outcome measure. However, open field activity monitoring is also associated with significant challenges: Open field activity measurements vary according to animal strain, age, sex, and circadian rhythm. In addition, room temperature, humidity, lighting, noise, and even odor can affect assessment outcomes. Overall, this manuscript provides a well-tested and standardized open field activity SOP for preclinical trials in animal models of neuromuscular diseases. We provide a discussion of important considerations, typical results, data analysis, and detail the strengths and weaknesses of open field testing. In addition, we provide recommendations for optimal study design when using open field activity in a preclinical trial.

  3. Mitochondrial oxidative enzyme activity in individual fibre types in hypo- and hyperthyroid rat skeletal muscles.

    Science.gov (United States)

    Johnson, M A; Turnbull, D M

    1984-04-01

    Quantitative cytochemical and biochemical techniques have been used in combination to study the response of mitochondrial oxidative enzymes in individual muscle fibre types to hypo- and hyperthyroidism. Hypothyroidism resulted in decreased activity of succinate dehydrogenase (SDH), L-glycerol-3-phosphate dehydrogenase (L-GPDH), and D-3-hydroxybutyrate dehydrogenase (D-HBDH) in all fibre types of both slow-twitch soleus and fast-twitch extensor digitorum longus (e.d.l.) muscles. In hyperthyroidism, only L-GPDH activity increased in e.d.l. but more marked increases were seen in soleus muscles, which also showed increased SDH activity. In addition to these alterations in the enzyme activity in individual fibre types the metabolic profile of the muscle is further modified by the hormone-induced interconversion of slow- to fast-twitch fibres and vice versa.

  4. Polar bears experience skeletal muscle atrophy in response to food deprivation and reduced activity in winter and summer

    Science.gov (United States)

    Harlow, Henry J.; Durner, George M.; Regehr, Eric V.; Rourke, Bryan C.; Robles, Manuel; Amstrup, Steven C.; Ben-David, Merav

    2017-01-01

    Abstract When reducing activity and using stored energy during seasonal food shortages, animals risk degradation of skeletal muscles, although some species avoid or minimize the resulting atrophy while experiencing these conditions during hibernation. Polar bears may be food deprived and relatively inactive during winter (when pregnant females hibernate and hunting success declines for other demographic groups) as well as summer (when sea ice retreats from key foraging habitats). We investigated muscle atrophy in samples of biceps femoris collected from free-ranging polar bears in the Southern Beaufort Sea (SBS) throughout their annual cycle. Atrophy was most pronounced in April–May as a result of food deprivation during the previous winter, with muscles exhibiting reduced protein concentration, increased water content, and lower creatine kinase mRNA. These animals increased feeding and activity in spring (when seal prey becomes more available), initiating a period of muscle recovery. During the following ice melt of late summer, ~30% of SBS bears abandon retreating sea ice for land; in August, these ‘shore’ bears exhibited no muscle atrophy, indicating that they had fully recovered from winter food deprivation. These individuals subsequently scavenged whale carcasses deposited by humans and by October, had retained good muscle condition. In contrast, ~70% of SBS bears follow the ice north in late summer, into deep water with less prey. These ‘ice’ bears fast; by October, they exhibited muscle protein loss and rapid changes in myosin heavy-chain isoforms in response to reduced activity. These findings indicate that, unlike other bears during winter hibernation, polar bears without food in summer cannot mitigate atrophy. Consequently, prolonged summer fasting resulting from climate change-induced ice loss creates a risk of greater muscle atrophy and reduced abilities to travel and hunt. PMID:28835844

  5. Polar bears experience skeletal muscle atrophy in response to food deprivation and reduced activity in winter and summer

    Science.gov (United States)

    Whiteman, John P.; Harlow, Henry J.; Durner, George M.; Regehr, Eric V.; Rourke, Bryan C.; Robles, Manuel; Amstrup, Steven C.; Ben-David, Merav

    2017-01-01

    When reducing activity and using stored energy during seasonal food shortages, animals risk degradation of skeletal muscles, although some species avoid or minimize the resulting atrophy while experiencing these conditions during hibernation. Polar bears may be food deprived and relatively inactive during winter (when pregnant females hibernate and hunting success declines for other demographic groups) as well as summer (when sea ice retreats from key foraging habitats). We investigated muscle atrophy in samples of biceps femoris collected from free-ranging polar bears in the Southern Beaufort Sea (SBS) throughout their annual cycle. Atrophy was most pronounced in April–May as a result of food deprivation during the previous winter, with muscles exhibiting reduced protein concentration, increased water content, and lower creatine kinase mRNA. These animals increased feeding and activity in spring (when seal prey becomes more available), initiating a period of muscle recovery. During the following ice melt of late summer, ~30% of SBS bears abandon retreating sea ice for land; in August, these ‘shore’ bears exhibited no muscle atrophy, indicating that they had fully recovered from winter food deprivation. These individuals subsequently scavenged whale carcasses deposited by humans and by October, had retained good muscle condition. In contrast, ~70% of SBS bears follow the ice north in late summer, into deep water with less prey. These ‘ice’ bears fast; by October, they exhibited muscle protein loss and rapid changes in myosin heavy-chain isoforms in response to reduced activity. These findings indicate that, unlike other bears during winter hibernation, polar bears without food in summer cannot mitigate atrophy. Consequently, prolonged summer fasting resulting from climate change-induced ice loss creates a risk of greater muscle atrophy and reduced abilities to travel and hunt.

  6. Polar bears experience skeletal muscle atrophy in response to food deprivation and reduced activity in winter and summer.

    Science.gov (United States)

    Whiteman, John P; Harlow, Henry J; Durner, George M; Regehr, Eric V; Rourke, Bryan C; Robles, Manuel; Amstrup, Steven C; Ben-David, Merav

    2017-01-01

    When reducing activity and using stored energy during seasonal food shortages, animals risk degradation of skeletal muscles, although some species avoid or minimize the resulting atrophy while experiencing these conditions during hibernation. Polar bears may be food deprived and relatively inactive during winter (when pregnant females hibernate and hunting success declines for other demographic groups) as well as summer (when sea ice retreats from key foraging habitats). We investigated muscle atrophy in samples of biceps femoris collected from free-ranging polar bears in the Southern Beaufort Sea (SBS) throughout their annual cycle. Atrophy was most pronounced in April-May as a result of food deprivation during the previous winter, with muscles exhibiting reduced protein concentration, increased water content, and lower creatine kinase mRNA. These animals increased feeding and activity in spring (when seal prey becomes more available), initiating a period of muscle recovery. During the following ice melt of late summer, ~30% of SBS bears abandon retreating sea ice for land; in August, these 'shore' bears exhibited no muscle atrophy, indicating that they had fully recovered from winter food deprivation. These individuals subsequently scavenged whale carcasses deposited by humans and by October, had retained good muscle condition. In contrast, ~70% of SBS bears follow the ice north in late summer, into deep water with less prey. These 'ice' bears fast; by October, they exhibited muscle protein loss and rapid changes in myosin heavy-chain isoforms in response to reduced activity. These findings indicate that, unlike other bears during winter hibernation, polar bears without food in summer cannot mitigate atrophy. Consequently, prolonged summer fasting resulting from climate change-induced ice loss creates a risk of greater muscle atrophy and reduced abilities to travel and hunt.

  7. High mature grain phytase activity in the Triticeae has evolved by duplication followed by neofunctionalization of the purple acid phosphatase phytase (PAPhy) gene

    DEFF Research Database (Denmark)

    Madsen, Claus Krogh; Dionisio, Giuseppe; Holme, Inger

    2013-01-01

    The phytase activity in food and feedstuffs is an important nutritional parameter. Members of the Triticeae tribe accumulate purple acid phosphatase phytases (PAPhy) during grain filling. This accumulation elevates mature grain phytase activities (MGPA) up to levels between ~650 FTU/kg for barley...

  8. Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication

    DEFF Research Database (Denmark)

    Mackey, Abigail L; Rasmussen, Lotte Klejs; Kadi, Fawzi

    2016-01-01

    muscles of one leg. Muscle biopsies were collected from the vastus lateralis muscles before and after stimulation (2.5 h and 2, 7, and 30 d) and were assessed for satellite cells and regeneration by immunohistochemistry and real-time RT-PCR, and we also measured telomere length. After injury, and compared...... activation of satellite cells and muscle remodeling during large-scale regeneration of injured human skeletal muscle.-Mackey, A. L., Rasmussen, L. K., Kadi, F., Schjerling, P., Helmark, I. C., Ponsot, E., Aagaard, P., Durigan, J. L. Q., Kjaer, M. Activation of satellite cells and the regeneration of human......With this study we investigated the role of nonsteroidal anti-inflammatory drugs (NSAIDs) in human skeletal muscle regeneration. Young men ingested NSAID [1200 mg/d ibuprofen (IBU)] or placebo (PLA) daily for 2 wk before and 4 wk after an electrical stimulation-induced injury to the leg extensor...

  9. PDH-E1alpha dephosphorylation and activation in human skeletal muscle during exercise

    DEFF Research Database (Denmark)

    Pilegaard, Henriette; Birk, Jesper Bratz; Sacchetti, Massimo

    2006-01-01

    . Phosphorylation had returned to resting levels at 3 h of exercise only in the control trial. Thus, an inverse association between PDH-E1a phosphorylation and PDHa activity exists. Short-term elevation in plasma FFA at rest increases PDH-E1a phosphorylation, but exercise overrules this effect of FFA on PDH-E1a...... extensor exercise at moderate intensity. During the 4-h resting period, activity of PDH in the active form (PDHa) did not change in either trial, yet phosphorylation of PDH-E1a site 1 (PDH-P1) and site 2 (PDH-P2) was elevated in the intralipid compared with the control trial. PDHa activity increased during...... exercise similarly in the two trials. After 3 h of exercise, PDHa activity remained elevated in the intralipid trial but returned to resting levels in the control trial. Accordingly, in both trials PDH-P1 and PDH-P2 decreased during exercise, and the decrease was more marked during intralipid infusion...

  10. [The opportunity to use combined stem cells transplantation for haemopoesis activation in the old and mature laboratory animals under the conditions of ionizing radiation].

    Science.gov (United States)

    Grebnev, D Iu; Maklakova, I Iu; Iastrebov, A P

    2014-01-01

    The objective of this work was to study the influence of combined transplantation of stem cells (multypotent mesenchimal stromal and haemopoetic stem cells) on the haemopoesis of old and mature laboratory animals under the condition of ionizing radiation. The result of the experiment shows that under physiological conditions the combined transplantation brings the erithropoesis activation, under the ionizing radiation conditions it brings the erythroid and granulocytopoesis activation. Moreover the combined MMSC and HSC transplantation gives cytoprotective action on the myeloid tissue due to decrease of cyto genically changed cells in the mature animals under the condition of ionizing radiation, but in the old animals this effect can be seen even under physiological condition. Combined transplantation of MMSC and GSC can be used in the mature and old laboratory animals under the conditions of ionising radiation for the haemopoesis activation.

  11. Structural maturation and brain activity predict future working memory capacity during childhood development.

    Science.gov (United States)

    Ullman, Henrik; Almeida, Rita; Klingberg, Torkel

    2014-01-29

    Human working memory capacity develops during childhood and is a strong predictor of future academic performance, in particular, achievements in mathematics and reading. Predicting working memory development is important for the early identification of children at risk for poor cognitive and academic development. Here we show that structural and functional magnetic resonance imaging data explain variance in children's working memory capacity 2 years later, which was unique variance in addition to that predicted using cognitive tests. While current working memory capacity correlated with frontoparietal cortical activity, the future capacity could be inferred from structure and activity in basal ganglia and thalamus. This gives a novel insight into the neural mechanisms of childhood development and supports the idea that neuroimaging can have a unique role in predicting children's cognitive development.

  12. Effect of biomass concentration on methane oxidation activity using mature compost and graphite granules as substrata.

    Science.gov (United States)

    Xie, S; O'Dwyer, T; Freguia, S; Pikaar, I; Clarke, W P

    2016-10-01

    Reported methane oxidation activity (MOA) varies widely for common landfill cover materials. Variation is expected due to differences in surface area, the composition of the substratum and culturing conditions. MOA per methanotrophic cell has been calculated in the study of natural systems such as lake sediments to examine the inherent conditions for methanotrophic activity. In this study, biomass normalised MOA (i.e., MOA per methanotophic cell) was measured on stabilised compost, a commonly used cover in landfills, and on graphite granules, an inert substratum widely used in microbial electrosynthesis studies. After initially enriching methanotrophs on both substrata, biomass normalised MOA was quantified under excess oxygen and limiting methane conditions in 160ml serum vials on both substrata and blends of the substrata. Biomass concentration was measured using the bicinchoninic acid assay for microbial protein. The biomass normalised MOA was consistent across all compost-to-graphite granules blends, but varied with time, reflecting the growth phase of the microorganisms. The biomass normalised MOA ranged from 0.069±0.006μmol CH4/mg dry biomass/h during active growth, to 0.024±0.001μmol CH4/mg dry biomass/h for established biofilms regardless of the substrata employed, indicating the substrata were equally effective in terms of inherent composition. The correlation of MOA with biomass is consistent with studies on methanotrophic activity in natural systems, but biomass normalised MOA varies by over 5 orders of magnitude between studies. This is partially due to different methods being used to quantify biomass, such as pmoA gene quantification and the culture dependent Most Probable Number method, but also indicates that long term exposure of materials to a supply of methane in an aerobic environment, as can occur in natural systems, leads to the enrichment and adaptation of types suitable for those conditions. Copyright © 2016 Elsevier Ltd. All rights

  13. Simulating the activation, contraction and movement of skeletal muscles using the bidomain model.

    Science.gov (United States)

    Lopez Rincon, A; Cantu, C; Soto, R; Shimoda, S

    2016-08-01

    A simulation of the muscle activation, contraction and movement is here presented. This system was developed based on the Bidomain mathematical model of the electrical propagation in muscles. This study shows an electrical stimuli input to a muscle and how this behave. The comparison between healthy subject and patient with muscle activation impairment is depicted, depending on whether the signal reaches a threshold. A 3D model of a bicep muscle and a forearm bone connected was constructed using OpenGL. This platform could be used for development of controllers for biomechatronic systems in future works. This kind of bioinspired model could be used for a better understanding of the neuromotor system.

  14. Regulation of pH in human skeletal muscle: adaptations to physical activity

    DEFF Research Database (Denmark)

    Juel, C

    2008-01-01

    -transport) and describes the contribution of each transport system in pH regulation at rest and during muscle activity. It is reported that the mechanisms involved in pH regulation can undergo adaptational changes in association with physical activity and that these changes are of functional importance....... resonance technique to exercise experiments including blood sampling and muscle biopsies. The present review characterizes the cellular buffering system as well as the most important membrane transport systems involved (Na(+)/H(+) exchange, Na-bicarbonate co-transport and lactate/H(+) co...

  15. Effect of exercise on skeletal muscle proteolytic enzyme activity and meat quality characteristics in Iberian pigs.

    Science.gov (United States)

    Lopez-Bote, C J; Toldrá, F; Daza, A; Ferrer, J M; Menoyo, D; Silió, L; Rodríguez, M C

    2008-05-01

    The effects of physical activity on performance, carcass traits, Psoas major lysosomal and exoprotease acitivies and meat quality were studied in 24 castrated male Iberian pigs during the last fattening period (from 111.1±SD: 5.2kg). Pigs were randomly distributed in three groups. Two groups receiving the same diet were reared in confinement, one housed in individual pens of 8m(2) (sedentary group) and the other was housed outdoor with daily (up to 2km) forced walking (exercise group). And one group was reared under the traditional production system walking daily several km and fed mostly with acorn from Quercus ilex and Quercus rotundifolia and grass (free-range group). No differences were found in performance and carcass traits. In exercised pigs a lower activity of cathepsin B+L and total cathepsins (P<0.05) was observed. Exercise induced the inhibition of dipeptidyl peptidases II and III and arginyl aminopeptidase and the activation of dipeptidyl peptidases IV and leucyl aminopeptidase (P<0.05). Although no effects on total free amino acids in Psoas major muscle were observed the concentration of branched chain amino acids decreased in the free-range pig group probably related to an increase in physical activity. Exercise had no effects in Psoas major postmortem tenderness and water holding capacity.

  16. Scleraxis is a transcriptional activator that regulates the expression of Tenomodulin, a marker of mature tenocytes and ligamentocytes.

    Science.gov (United States)

    Shukunami, Chisa; Takimoto, Aki; Nishizaki, Yuriko; Yoshimoto, Yuki; Tanaka, Seima; Miura, Shigenori; Watanabe, Hitomi; Sakuma, Tetsushi; Yamamoto, Takashi; Kondoh, Gen; Hiraki, Yuji

    2018-02-16

    Tenomodulin (Tnmd) is a type II transmembrane glycoprotein predominantly expressed in tendons and ligaments. We found that scleraxis (Scx), a member of the Twist-family of basic helix-loop-helix transcription factors, is a transcriptional activator of Tnmd expression in tenocytes. During embryonic development, Scx expression preceded that of Tnmd. Tnmd expression was nearly absent in tendons and ligaments of Scx-deficient mice generated by transcription activator-like effector nucleases-mediated gene disruption. Tnmd mRNA levels were dramatically decreased during serial passages of rat tenocytes. Scx silencing by small interfering RNA significantly suppressed endogenous Tnmd mRNA levels in tenocytes. Mouse Tnmd contains five E-box sites in the ~1-kb 5'-flanking region. A 174-base pair genomic fragment containing a TATA box drives transcription in tenocytes. Enhancer activity was increased in the upstream region (-1030 to -295) of Tnmd in tenocytes, but not in NIH3T3 and C3H10T1/2 cells. Preferential binding of both Scx and Twist1 as a heterodimer with E12 or E47 to CAGATG or CATCTG and transactivation of the 5'-flanking region were confirmed by electrophoresis mobility shift and dual luciferase assays, respectively. Scx directly transactivates Tnmd via these E-boxes to positively regulate tenocyte differentiation and maturation.

  17. Antimicrobial activity of crude epicarp and seed extracts from mature avocado fruit (Persea americana) of three cultivars.

    Science.gov (United States)

    Raymond Chia, Teck Wah; Dykes, Gary A

    2010-07-01

    The epicarp and seed of Persea Americana Mill. var. Hass (Lauraceae), Persea Americana Mill. var. Shepard, and Persea americana Mill. var Fuerte cultivars of mature avocados (n = 3) were ground separately and extracted with both absolute ethanol and distilled water. Extracts were analyzed for antimicrobial activity using the microtiter broth microdilution assay against four Gram-positive bacteria, six Gram-negative bacteria, and one yeast. Antimicrobial activity against two molds was determined by the hole plate method. The ethanol extracts showed antimicrobial activity (104.2-416.7 microg/mL) toward both Gram-positive and Gram-negative bacteria (except Escherichia coli), while inhibition of the water extracts was only observed for Listeria monocytogenes (93.8-375.0 microg/mL) and Staphylococcus epidermidis (354.2 microg/mL). The minimum concentration required to inhibit Zygosaccharomyces bailii was 500 microg/mL for the ethanol extracts, while no inhibition was observed for the water extracts. No inhibition by either ethanol or water extracts was observed against Penicillium spp. and Aspergillus flavus.

  18. Natural Killer Cells Are Activated by Lactic Acid Bacteria-Matured Dendritic Cells

    DEFF Research Database (Denmark)

    Fink, Lisbeth Nielsen; Christensen, Hanne Risager; Frøkiær, Hanne

    of certain lactic acid bacteria has been shown to increase in vivo NK cytotoxicity. Here, we investigated how human gut flora-derived lactobacilli affect NK cells in vitro, by measuring proliferation and IFN-gamma production of human NK cells upon bacterial stimulation. Human peripheral blood NK cells were....... In contrast, a Lactobacillus paracasei strain caused the NK cells to proliferate only in the presence of monocytes. These results demonstrate that various strains of lactobacilli have the capacity to activate NK cells in vitro, in a monocyte dependent or independent way. Hence, the encounter of NK cells...

  19. Presence and seeding activity of pathological prion protein (PrP(TSE in skeletal muscles of white-tailed deer infected with chronic wasting disease.

    Directory of Open Access Journals (Sweden)

    Martin L Daus

    Full Text Available Chronic wasting disease (CWD is a contagious, rapidly spreading transmissible spongiform encephalopathy (TSE, or prion disease, occurring in cervids such as white tailed-deer (WTD, mule deer or elk in North America. Despite efficient horizontal transmission of CWD among cervids natural transmission of the disease to other species has not yet been observed. Here, we report for the first time a direct biochemical demonstration of pathological prion protein PrP(TSE and of PrP(TSE-associated seeding activity, the static and dynamic biochemical markers for biological prion infectivity, respectively, in skeletal muscles of CWD-infected cervids, i. e. WTD for which no clinical signs of CWD had been recognized. The presence of PrP(TSE was detected by Western- and postfixed frozen tissue blotting, while the seeding activity of PrP(TSE was revealed by protein misfolding cyclic amplification (PMCA. Semi-quantitative Western blotting indicated that the concentration of PrP(TSE in skeletal muscles of CWD-infected WTD was approximately 2000-10,000-fold lower than in brain tissue. Tissue-blot-analyses revealed that PrP(TSE was located in muscle-associated nerve fascicles but not, in detectable amounts, in myocytes. The presence and seeding activity of PrP(TSE in skeletal muscle from CWD-infected cervids suggests prevention of such tissue in the human diet as a precautionary measure for food safety, pending on further clarification of whether CWD may be transmissible to humans.

  20. Effect of sprint cycle training on activities of antioxidant enzymes in human skeletal muscle

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Apple, F. S.; Sjödin, B.

    1996-01-01

    (P anaerobic capacity in the trained muscle. The present study demonstrates that intermittent sprint cycle training that induces an enhanced capacity for anaerobic energy generation also improves......The effect of intermittent sprint cycle training on the level of muscle antioxidant enzyme protection was investigated. Resting muscle biopsies, obtained before and after 6 wk of training and 3, 24, and 72 h after the final session of an additional 1 wk of more frequent training, were analyzed...... for activities of the antioxidant enzymes glutathione peroxidase (GPX), glutathione reductase (GR), and superoxide dismutase (SOD). Activities of several muscle metabolic enzymes were determined to assess the effectiveness of the training. After the first 6-wk training period, no change in GPX, GR, or SOD...

  1. Adapted physical exercise enhances activation and differentiation potential of satellite cells in the skeletal muscle of old mice.

    Science.gov (United States)

    Cisterna, Barbara; Giagnacovo, Marzia; Costanzo, Manuela; Fattoretti, Patrizia; Zancanaro, Carlo; Pellicciari, Carlo; Malatesta, Manuela

    2016-05-01

    During ageing, a progressive loss of skeletal muscle mass and a decrease in muscle strength and endurance take place, in the condition termed sarcopenia. The mechanisms of sarcopenia are complex and still unclear; however, it is known that muscle atrophy is associated with a decline in the number and/or efficiency of satellite cells, the main contributors to muscle regeneration. Physical exercise proved beneficial in sarcopenia; however, knowledge of the effect of adapted physical exercise on the myogenic properties of satellite cells in aged muscles is limited. In this study the amount and activation state of satellite cells as well as their proliferation and differentiation potential were assessed in situ by morphology, morphometry and immunocytochemistry at light and transmission electron microscopy on 28-month-old mice submitted to adapted aerobic physical exercise on a treadmill. Sedentary age-matched mice served as controls, and sedentary adult mice were used as a reference for an unperturbed control at an age when the capability of muscle regeneration is still high. The effect of physical exercise in aged muscles was further analysed by comparing the myogenic potential of satellite cells isolated from old running and old sedentary mice using an in vitro system that allows observation of the differentiation process under controlled experimental conditions. The results of this ex vivo and in vitro study demonstrated that adapted physical exercise increases the number and activation of satellite cells as well as their capability to differentiate into structurally and functionally correct myotubes (even though the age-related impairment in myotube formation is not fully reversed): this evidence further supports adapted physical exercise as a powerful, non-pharmacological approach to counteract sarcopenia and the age-related deterioration of satellite cell capabilities even at very advanced age. © 2016 Anatomical Society.

  2. FHL1 activates myostatin signalling in skeletal muscle and promotes atrophy

    OpenAIRE

    Kemp, P; Lee, JY; lori, O; Wells, D

    2015-01-01

    Myostatin is a TGFβ family ligand that reduces muscle mass. In cancer cells, TGFβ signalling is increased by the protein FHL1. Consequently, FHL1 may promote signalling by myostatin. We therefore tested the ability of FHL1 to regulate myostatin function. FHL1 increased the myostatin activity on a SMAD reporter and increased myostatin dependent myotube wasting. In mice, independent expression of myostatin reduced fibre diameter whereas FHL1 increased fibre diameter, both consistent with previo...

  3. Instantaneous quantification of skeletal muscle activation, power production, and fatigue during cycle ergometry.

    Science.gov (United States)

    Coelho, A C; Cannon, D T; Cao, R; Porszasz, J; Casaburi, R; Knorst, M M; Rossiter, H B

    2015-03-01

    A rapid switch from hyperbolic to isokinetic cycling allows the velocity-specific decline in maximal power to be measured, i.e., fatigue. We reasoned that, should the baseline relationship between isokinetic power (Piso) and electromyography (EMG) be reproducible, then contributions to fatigue may be isolated from 1) the decline in muscle activation (muscle activation fatigue); and 2) the decline in Piso at a given activation (muscle fatigue). We hypothesized that the EMG-Piso relationship is linear, velocity dependent, and reliable for instantaneous fatigue assessment at intolerance during and following whole body exercise. Healthy participants (n = 13) completed short (5 s) variable-effort isokinetic bouts at 50, 70, and 100 rpm to characterize baseline EMG-Piso. Repeated ramp incremental exercise tests were terminated with maximal isokinetic cycling (5 s) at 70 rpm. Individual baseline EMG-Piso relationships were linear (r(2) = 0.95 ± 0.04) and velocity dependent (analysis of covariance). Piso at intolerance (two legs, 335 ± 88 W) was ∼45% less than baseline [630 ± 156 W, confidence interval of the difference (CIDifference) 211, 380 W, P fatigue and muscle fatigue (one leg) were 97 ± 55 and 60 ± 50 W, respectively. Mean bias ± limits of agreement for reproducibility were as follows: baseline Piso 1 ± 30 W; Piso at 0-min recovery 3 ± 35 W; and EMG at Piso 3 ± 14%. EMG power is linear, velocity dependent, and reproducible. Deviation from this relationship at the limit of tolerance can quantify the "activation" and "muscle" related components of fatigue during cycling. Copyright © 2015 the American Physiological Society.

  4. p38 MAPK activation and H3K4 trimethylation is decreased by lactate in vitro and high intensity resistance training in human skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Lena Willkomm

    Full Text Available Exercise induces adaptation of skeletal muscle by acutely modulating intracellular signaling, gene expression, protein turnover and myogenic activation of skeletal muscle stem cells (Satellite cells, SCs. Lactate (La-induced metabolic stimulation alone has been shown to modify SC proliferation and differentiation. Although the mechanistic basis remains elusive, it was demonstrated that La affects signaling via p38 mitogen activated protein kinase (p38 MAPK which might contribute to trimethylation of histone 3 lysine 4 (H3K4me3 known to regulate satellite cell proliferation and differentiation. We investigated the effects of La on p38 MAPK and H3K4me3 in a model of activated SCs. Differentiating C2C12 myoblasts were treated with La (20 mM and samples analysed using qRT-PCR, immunofluorescence, and western blotting. We determined a reduction of p38 MAPK phosphorylation, decreased H3K4me3 and reduced expression of Myf5, myogenin, and myosin heavy chain (MHC leading to decreased differentiation of La-treated C2C12 cells after 5 days of repeated La treatment. We further investigated whether this regulatory pathway would be affected in human skeletal muscle by the application of two different resistance exercise regimes (RE associated with distinct metabolic demands and blood La accumulation. Muscle biopsies were obtained 15, 30 min, 1, 4, and 24 h post exercise after moderate intensity RE (STD vs. high intensity RE (HIT. Consistent with in vitro results, reduced p38 phosphorylation and blunted H3K4me3 were also observed upon metabolically demanding HIT RE in human skeletal muscle. Our data provide evidence that La-accumulation acutely affects p38 MAPK signaling, gene expression and thereby cell differentiation and adaptation in vitro, and likely in vivo.

  5. p38 MAPK activation and H3K4 trimethylation is decreased by lactate in vitro and high intensity resistance training in human skeletal muscle.

    Science.gov (United States)

    Willkomm, Lena; Gehlert, Sebastian; Jacko, Daniel; Schiffer, Thorsten; Bloch, Wilhelm

    2017-01-01

    Exercise induces adaptation of skeletal muscle by acutely modulating intracellular signaling, gene expression, protein turnover and myogenic activation of skeletal muscle stem cells (Satellite cells, SCs). Lactate (La)-induced metabolic stimulation alone has been shown to modify SC proliferation and differentiation. Although the mechanistic basis remains elusive, it was demonstrated that La affects signaling via p38 mitogen activated protein kinase (p38 MAPK) which might contribute to trimethylation of histone 3 lysine 4 (H3K4me3) known to regulate satellite cell proliferation and differentiation. We investigated the effects of La on p38 MAPK and H3K4me3 in a model of activated SCs. Differentiating C2C12 myoblasts were treated with La (20 mM) and samples analysed using qRT-PCR, immunofluorescence, and western blotting. We determined a reduction of p38 MAPK phosphorylation, decreased H3K4me3 and reduced expression of Myf5, myogenin, and myosin heavy chain (MHC) leading to decreased differentiation of La-treated C2C12 cells after 5 days of repeated La treatment. We further investigated whether this regulatory pathway would be affected in human skeletal muscle by the application of two different resistance exercise regimes (RE) associated with distinct metabolic demands and blood La accumulation. Muscle biopsies were obtained 15, 30 min, 1, 4, and 24 h post exercise after moderate intensity RE (STD) vs. high intensity RE (HIT). Consistent with in vitro results, reduced p38 phosphorylation and blunted H3K4me3 were also observed upon metabolically demanding HIT RE in human skeletal muscle. Our data provide evidence that La-accumulation acutely affects p38 MAPK signaling, gene expression and thereby cell differentiation and adaptation in vitro, and likely in vivo.

  6. New skeletal sesquiterpenoids, caprariolides A-D, from Capraria biflora and their insecticidal activity.

    Science.gov (United States)

    Collins, D O; Gallimore, W A; Reynolds, W F; Williams, L A; Reese, P B

    2000-11-01

    Four structurally novel isomeric sesquiterpenes have been isolated from the aerial parts of Capraria biflora. Caprariolides A (1), B (2), C (3), and D (4) have been determined by NMR spectroscopy experiments to be the (3S,5S,9R), (3R,5S,9R), (3R,5R,9R), and (3S,5R, 9R) isomers of 7-(furan-3'-yl)-3,9-dimethyl-1-oxaspiro[4. 5]dec-6-en-2-one, respectively. Both 1 and 2 were found to exhibit insecticidal activity against adult Cylas formicarius elegantulus, one of the most destructive insect pests of the sweet potato, Ipomoea sp.

  7. Administered activity optimization in skeletal scanning using MDP labeled 99Tcm

    International Nuclear Information System (INIS)

    Perez Diaz, Marlen; Quevedo Garcia, Jose; Diaz Rizo, Oscar; Dopico Hernandez, Rolando; Estevez Aparicio, Eric; Viamonte Marin, Alfredo; Cabrera Gorrin, Orlando

    2002-01-01

    The objective of this study was to determine the minimum activity of the MDP labeled 99Tcm which is able to produce both, good image quality in the gamma camera and better radiological protection for the patient. Four samples of 18 patients were taken. A different protocol was applied to each sample. Each sample was divided into 3 groups of 6 patients each. The activity applied to each group was 293 MBq, 430 MBq and 598 MBq. Each study had 5 images to be assessed by expert criterion: Left Side Skull, Fore Thorax, Dorsal-cervix Column, Dorsal-lumbar Column and Rear Pelvis. The Number and Rate of Counts, the Signal/Background (S/B) ratio and the patient's sizes were taken as variables for analysis. S/B ratio was the only parameter able to construct a discriminant function of the image quality. Significant difference between the image quality with 598 MBq and 430 MBq (p=0,03) were not detected. The value of 430 MBq is enough to achieve good image quality with Protocol 4 for all the images except for the skull (Au)

  8. Maturity Models

    DEFF Research Database (Denmark)

    Lasrado, Lester Allan; Vatrapu, Ravi

    2016-01-01

    Recent advancements in set theory and readily available software have enabled social science researchers to bridge the variable-centered quantitative and case-based qualitative methodological paradigms in order to analyze multi-dimensional associations beyond the linearity assumptions, aggregate...... effects, unicausal reduction, and case specificity. Based on the developments in set theoretical thinking in social sciences and employing methods like Qualitative Comparative Analysis (QCA), Necessary Condition Analysis (NCA), and set visualization techniques, in this position paper, we propose...... and demonstrate a new approach to maturity models in the domain of Information Systems. This position paper describes the set-theoretical approach to maturity models, presents current results and outlines future research work....

  9. Seasonal variations in sexual activity and endocrine changes associated with follicular maturation and development in the Peulh ewe

    International Nuclear Information System (INIS)

    Yenikoye, A.

    1988-01-01

    Annual variations in sexual activity (oestrus and ovulation) and in the endocrine balances which govern follicular maturation and ovulation (the ovarian hormones progesterone and oestradiol-17β, and the pituitary hormones FSH, LH and PRL) were studied in the Peulh ewes of Niger. It was found that two types of disturbances in ovarian function limited the fertility of ewes in semi-arid environment: (a) persistent corpora lutea which occurred in 14% of animals and affected 2.2% of oestrous cycles in the course of the year. Their appearance coincided with increasing humidity (in June and July) or daily temperature (December to April); and (b) seasonal anoestrus, observed in 67% of animals from December to April, and coinciding with maximum daily temperatures. These ovarian anomalies were associated with a weak endogenous rhythm of LH secretion without any change in feedback from the ovarian steroids progesterone and oestradiol-17β on the hypothalamic-pituitary axis. A study of seasonal variations in levels of the gonadotrophic hormones indicated that there may be a weaker than usual dependence between the ovary and the pituitary during periods of anomalous sexual activity in Peulh ewes. The results presented suggest that both types of ovarian dysfunction observed in certain Peulh ewes may reflect poorer adaptation to the semi-arid climate. (author). 54 refs, 8 figs, 3 tabs

  10. The cAMP Response Element Binding protein (CREB) is activated by Insulin-like Growth Factor-1 (IGF-1) and regulates myostatin gene expression in skeletal myoblast

    International Nuclear Information System (INIS)

    Zuloaga, R.; Fuentes, E.N.; Molina, A.; Valdés, J.A.

    2013-01-01

    Highlights: •IGF-1 induces the activation of CREB via IGF-1R/PI3K/PLC signaling pathway. •Calcium dependent signaling pathways regulate myostatin gene expression. •IGF-1 regulates myostatin gene expression via CREB transcription in skeletal myoblast. -- Abstract: Myostatin, a member of the Transforming Growth Factor beta (TGF-β) superfamily, plays an important role as a negative regulator of skeletal muscle growth and differentiation. We have previously reported that IGF-1 induces a transient myostatin mRNA expression, through the activation of the Nuclear Factor of Activated T cells (NFAT) in an IP 3 /calcium-dependent manner. Here we examined the activation of CREB transcription factor as downstream targets of IGF-1 during myoblast differentiation and its role as a regulator of myostatin gene expression. In cultured skeletal myoblast, IGF-1 induced the phosphorylation and transcriptional activation of CREB via IGF-1 Receptor/Phosphatidylinositol 3-Kinase (PI3K)/Phospholipase C gamma (PLC γ), signaling pathways. Also, IGF-1 induced calcium-dependent molecules such as Calmodulin Kinase II (CaMK II), Extracellular signal-regulated Kinases (ERK), Protein Kinase C (PKC). Additionally, we examined myostatin mRNA levels and myostatin promoter activity in differentiated myoblasts stimulated with IGF-1. We found a significant increase in mRNA contents of myostatin and its reporter activity after treatment with IGF-1. The expression of myostatin in differentiated myoblast was downregulated by the transfection of siRNA–CREB and by pharmacological inhibitors of the signaling pathways involved in CREB activation. By using pharmacological and genetic approaches together these data demonstrate that IGF-1 regulates the myostatin gene expression via CREB transcription factor during muscle cell differentiation

  11. The cAMP Response Element Binding protein (CREB) is activated by Insulin-like Growth Factor-1 (IGF-1) and regulates myostatin gene expression in skeletal myoblast

    Energy Technology Data Exchange (ETDEWEB)

    Zuloaga, R. [Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago (Chile); Fuentes, E.N.; Molina, A. [Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago (Chile); Interdisciplinary Center for Aquaculture Research (INCAR), Víctor Lamas 1290, PO Box 160-C, Concepción (Chile); Valdés, J.A., E-mail: jvaldes@unab.cl [Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago (Chile); Interdisciplinary Center for Aquaculture Research (INCAR), Víctor Lamas 1290, PO Box 160-C, Concepción (Chile)

    2013-10-18

    Highlights: •IGF-1 induces the activation of CREB via IGF-1R/PI3K/PLC signaling pathway. •Calcium dependent signaling pathways regulate myostatin gene expression. •IGF-1 regulates myostatin gene expression via CREB transcription in skeletal myoblast. -- Abstract: Myostatin, a member of the Transforming Growth Factor beta (TGF-β) superfamily, plays an important role as a negative regulator of skeletal muscle growth and differentiation. We have previously reported that IGF-1 induces a transient myostatin mRNA expression, through the activation of the Nuclear Factor of Activated T cells (NFAT) in an IP{sub 3}/calcium-dependent manner. Here we examined the activation of CREB transcription factor as downstream targets of IGF-1 during myoblast differentiation and its role as a regulator of myostatin gene expression. In cultured skeletal myoblast, IGF-1 induced the phosphorylation and transcriptional activation of CREB via IGF-1 Receptor/Phosphatidylinositol 3-Kinase (PI3K)/Phospholipase C gamma (PLC γ), signaling pathways. Also, IGF-1 induced calcium-dependent molecules such as Calmodulin Kinase II (CaMK II), Extracellular signal-regulated Kinases (ERK), Protein Kinase C (PKC). Additionally, we examined myostatin mRNA levels and myostatin promoter activity in differentiated myoblasts stimulated with IGF-1. We found a significant increase in mRNA contents of myostatin and its reporter activity after treatment with IGF-1. The expression of myostatin in differentiated myoblast was downregulated by the transfection of siRNA–CREB and by pharmacological inhibitors of the signaling pathways involved in CREB activation. By using pharmacological and genetic approaches together these data demonstrate that IGF-1 regulates the myostatin gene expression via CREB transcription factor during muscle cell differentiation.

  12. AMP kinase expression and activity in human skeletal muscle: effects of immobilization, retraining, and creatine supplementation

    DEFF Research Database (Denmark)

    Eijnde, Bert O.; Derave, Wim; Wojtaszewski, Jørgen

    2005-01-01

    The effects of leg immobilization and retraining in combination with oral creatine intake on muscle AMP-activated protein kinase (AMPK) protein expression and phosphorylation status were investigated. A double-blind trial was performed in young healthy volunteers (n = 22). A cast immobilized...... the right leg for 2 wk, whereafter the knee-extensor muscles of that leg were retrained for 6 wk. Half of the subjects received creatine monohydrate throughout the study (Cr; from 15 g down to 2.5 g daily), and the others ingested placebo (P; maltodextrin). Before and after immobilization and retraining...... that immobilization-induced muscle inactivity for 2 wk does not alter AMPK a1-, a2-, and ß2-subunit expression or a-AMPK phosphorylation status. Furthermore, the present observations indicate that AMPK probably is not implicated in the previously reported beneficial effects of oral creatine supplementation on muscle...

  13. [THE CHANGES OF NOCICEPTIVE THRESHOLD AND ACTIVITY OF THE ADENYLYL CYCLASE SYSTEM IN THE SKELETAL MUSCLES OF RATS WITH ACUTE AND MILD TYPE 1 DIABETES MELLITUS ].

    Science.gov (United States)

    Shipilov, V N; Trost, A M; Chistyakova, O V; Derkach, K V; Shpakov, A O

    2016-02-01

    Diabetic peripheral neuropathy (DPN) is one of the most common complications of the type 1 diabetes mellitus (DM1). The aim of the work was to study the dynamics of a painful DPN and functional state of the hormone-sensitive ACSS in the skeletal muscles of rats with the models of acute and mild DM1, as well as the study of impact on them of insulin therapy with different ways of hormone delivery - intranasal and peripheral. In both models of DM1, the level of nociceptive threshold in rats decreased and the stimulatory effects of guanine nucleotides (GppNHp) and adrenergic agonists (isoproterenol, BRL-37344) on adenylyl cyclase (AC) activity were attenuated. The AC stimulating effect of relaxin decreased in animals with acute DM1, but in mild DM1, the decrease was insignificant. Peripheral administration of insulin in rats with acute DM1 increased the nociceptive threshold and partially restored the AC effect of ß 3-agonist BRL-37344. Intranasal administration of insulin in rats with DM1 also increased the nociceptive threshold and partially restored the basal and BRL-37344-stimulated AC activity in the skeletal muscles of diabetic animals. Thus, in the skeletal muscles of rats with acute and mild DM1 the nociceptive sensitivity and the functions of ACSS were disturbed, and they were partially restored by the treatment with peripheral (acute DM1) or intranasal (mild DM1) insulin.

  14. The exercised skeletal muscle: a review

    Directory of Open Access Journals (Sweden)

    Marina Marini

    2010-09-01

    Full Text Available The skeletal muscle is the second more plastic tissue of the body - second to the nervous tissue only. In fact, both physical activity and inactivity contribute to modify the skeletal muscle, by continuous signaling through nerve impulses, mechanical stimuli and humoral clues. In turn, the skeletal muscle sends signals to the body, thus contributing to its homeostasis. We'll review here the contribute of physical exercise to the shaping of skeletal muscle, to the adaptation of its mass and function to the different needs imposed by different physical activities and to the attainment of the health benefits associated with active skeletal muscles. Focus will primarily be on the molecular pathways and on gene regulation that result in skeletal muscle adaptation to exercise.

  15. Fluoride therapy for osteoporosis: characterization of the skeletal response by serial measurements of serum alkaline phosphatase activity.

    Science.gov (United States)

    Farley, S M; Wergedal, J E; Smith, L C; Lundy, M W; Farley, J R; Baylink, D J

    1987-03-01

    Optimum use of fluoride therapy for osteoporosis requires a sensitive and convenient index of the skeletal response to fluoride. Since previous studies had shown that serum alkaline phosphatase activity (SALP) was increased in response to fluoride therapy, we examined serial measurements of SALP in 53 osteoporotics treated with 66 to 110 mg of sodium fluoride (NaF) for 12 to 91 months. SALP was increased in 87% of the subjects during therapy with fluoride. The increase in SALP was thought to reflect the osteogenic action of fluoride based on the findings that SALP correlated with both trabecular bone area (r = .81, P less than .001) and osteoid length (r = .67, P less than .01) in iliac crest biopsies, predicted increased bone density on spinal radiographs in response to fluoride therapy with an 87% accuracy, and predicted decreased back pain in response to fluoride with a 91% accuracy. In addition, the SALP response to fluoride was seen earlier than other therapeutic responses as indicated by the findings that the tau 1/2 for the SALP response (ie, time for 1/2 of the patients to show a significant response) was significantly less (1.2 +/- 0.3 yr) than that for the pain response (1.6 +/- 0.3 yr, P less than .05) or that for the radiographic response (3.7 +/- 0.5 yr, P less than .001). Although most patients responded to fluoride with an increase in SALP, evaluation of the kinetics of the SALP response to fluoride revealed marked interpatient variation.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Fiber type conversion by PGC-1α activates lysosomal and autophagosomal biogenesis in both unaffected and Pompe skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Shoichi Takikita

    2010-12-01

    Full Text Available PGC-1α is a transcriptional co-activator that plays a central role in the regulation of energy metabolism. Our interest in this protein was driven by its ability to promote muscle remodeling. Conversion from fast glycolytic to slow oxidative fibers seemed a promising therapeutic approach in Pompe disease, a severe myopathy caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA which is responsible for the degradation of glycogen. The recently approved enzyme replacement therapy (ERT has only a partial effect in skeletal muscle. In our Pompe mouse model (KO, the poor muscle response is seen in fast but not in slow muscle and is associated with massive accumulation of autophagic debris and ineffective autophagy. In an attempt to turn the therapy-resistant fibers into fibers amenable to therapy, we made transgenic KO mice expressing PGC-1α in muscle (tgKO. The successful switch from fast to slow fibers prevented the formation of autophagic buildup in the converted fibers, but PGC-1α failed to improve the clearance of glycogen by ERT. This outcome is likely explained by an unexpected dramatic increase in muscle glycogen load to levels much closer to those observed in patients, in particular infants, with the disease. We have also found a remarkable rise in the number of lysosomes and autophagosomes in the tgKO compared to the KO. These data point to the role of PGC-1α in muscle glucose metabolism and its possible role as a master regulator for organelle biogenesis - not only for mitochondria but also for lysosomes and autophagosomes. These findings may have implications for therapy of lysosomal diseases and other disorders with altered autophagy.

  17. Phosphorylation of inhibitor-2 and activation of MgATP-dependent protein phosphatase by rat skeletal muscle glycogen synthase kinase

    International Nuclear Information System (INIS)

    Hegazy, M.G.; Reimann, E.M.; Thysseril, T.J.; Schlender, K.K.

    1986-01-01

    Rat skeletal muscle contains a glycogen synthase kinase (GSK-M) which is not stimulated by Ca 2+ or cAMP. This kinase has an apparent Mr of 62,000 and uses ATP but not GTP as a phosphoryl donor. GSK-M phosphorylated glycogen synthase at sites 2 and 3. It phosphorylated ATP-citrate lyase and activated MgATP-dependent phosphatase in the presence of ATP but not GTP. As expected, the kinase also phosphorylated phosphatase inhibitor 2 (I-2). Phosphatase incorporation reached approximately 0.3 mol/mol of I-2. Phosphopeptide maps were obtained by digesting 32 P-labeled I-2 with trypsin and separating the peptides by reversed phase HPLC. Two partially separated 32 P-labeled peaks were obtained when I-2 was phosphorylated with either GSK-M or glycogen synthase kinase 3 (GSK-3) and these peptides were different from those obtained when I-2 was phosphorylated with the catalytic subunit of cAMP-dependent protein kinase (CSU) or casein kinase II (CK-II). When I-2 was phosphorylated with GSK-M or GSK-3 and cleaved by CNBr, a single radioactive peak was obtained. Phosphoamino acid analysis showed that I-2 was phosphorylated by GSK-M or GSK-3 predominately in Thr whereas CSU and CK-II phosphorylated I-2 exclusively in Ser. These results indicate that GSK-M is similar to GSK-3 and to ATP-citrate lyase kinase. However, it appears to differ in Mr from ATP-citrate lyase kinase and it differs from GSK-3 in that it phosphorylates glycogen synthase at site 2 and it does not use GTP as a phosphoryl donor

  18. Contributions of central command and muscle feedback to sympathetic nerve activity in contracting human skeletal muscle

    Directory of Open Access Journals (Sweden)

    Daniel eBoulton

    2016-05-01

    Full Text Available During voluntary contractions, muscle sympathetic nerve activity (MSNA to contracting muscles increases in proportion to force but the underlying mechanisms are not clear. To shed light on these mechanisms, particularly the influences of central command and muscle afferent feedback, the present study tested the hypothesis that MSNA is greater during voluntary compared with electrically-evoked contractions. Seven male subjects performed a series of 1-minute isometric dorsiflexion contractions (left leg separated by 2-minute rest periods, alternating between voluntary and electrically-evoked contractions at similar forces (5-10 % of maximum. MSNA was recorded continuously (microneurography from the left peroneal nerve and quantified from cardiac-synchronised, negative-going spikes in the neurogram. Compared with pre-contraction values, MSNA increased by 51 ± 34 % (P 0.05. MSNA analysed at 15-s intervals revealed that this effect of voluntary contraction appeared 15-30 s after contraction onset (P < 0.01, remained elevated until the end of contraction, and disappeared within 15 s after contraction. These findings suggest that central command, and not feedback from contracting muscle, is the primary mechanism responsible for the increase in MSNA to contracting muscle. The time-course of MSNA suggests that there is a longer delay in the onset of this effect compared with its cessation after contraction.

  19. Skeletal effects of central nervous system active drugs: anxiolytics, sedatives, antidepressants, lithium and neuroleptics.

    Science.gov (United States)

    Vestergaard, Peter

    2008-09-01

    Many central nervous system active drugs can alter postural balance, increasing the risk of fractures. Anxiolytics and sedatives include the benzodiazepines, and these have been associated with a limited increase in the risk of fractures, even at low doses, probably from an increased risk of falls. No systematic differences have been shown between benzodiazepines with long and short half-lives. Although the increase in risk of fractures was limited, care must still be taken when prescribing for older fall-prone subjects at risk of osteoporosis. Neuroleptics may be associated with a decrease in bone mineral density and a very limited increase in fracture risk. Antidepressants are associated with a dose-dependent increase in the risk of fractures. The increase in relative risk of fractures seems to be larger with selective serotonin reuptake inhibitors (SSRIs) than with tricyclic antidepressants. The reason for this is not known but may be linked to serotonin effects on bone cells and the risk of falls. With the wide use of SSRIs, more research is needed. Lithium is associated with a decrease in the risk of fractures. This may be linked to its effects on the Wnt glycoprotein family, which is a specialised signalling system for certain cell types.

  20. Influence of Skeletal Muscle Carnosine Content on Fatigue during Repeated Resistance Exercise in Recreationally Active Women

    Science.gov (United States)

    Varanoske, Alyssa N.; Hoffman, Jay R.; Church, David D.; Baker, Kayla M.; Dodd, Sarah J.; Coker, Nicholas A.; Oliveira, Leonardo P.; Dawson, Virgil L.; Stout, Jeffrey R.

    2017-01-01

    Carnosine is a naturally occurring intramuscular dipeptide that is thought to attenuate fatigue during high-intensity exercise. Carnosine content is influenced by various factors, including gender and diet. Despite research reporting that carnosine content is lower in women compared to men and lower in vegetarians compared to omnivores, no investigations have examined carnosine content in women based on dietary protein intake and its effect on muscle fatigue. Twenty recreationally active women were assigned to either a high (HI; n = 5), moderate (MOD; n = 10), or low (LO; n = 5) group based upon intramuscular carnosine content of the vastus lateralis. Each participant underwent two unilateral maximal voluntary isometric contractions (MVIC) of the knee extensors separated by an isokinetic exercise protocol consisting of five sets of 50 repeated maximal unilateral contractions. Magnitude-based inferences were used to analyze group differences. Percent decline in rate of force development and peak torque (PT) during the MVICs and changes in PT and mean torque during the muscle-fatiguing protocol were lower in HI compared to both MOD and LO. Additionally, absolute and relative dietary protein intake were greater in HI compared to MOD or LO. Results indicated that greater intramuscular carnosine content was reflective of greater dietary protein intake and that individuals with higher carnosine content displayed a greater attenuation of fatigue compared to those with lower carnosine. PMID:28880219

  1. Nutritional status modulates plasma leptin, AMPK and TOR activation, and mitochondrial biogenesis: Implications for cell metabolism and growth in skeletal muscle of the fine flounder.

    Science.gov (United States)

    Fuentes, Eduardo N; Safian, Diego; Einarsdottir, Ingibjörg Eir; Valdés, Juan Antonio; Elorza, Alvaro A; Molina, Alfredo; Björnsson, Björn Thrandur

    2013-06-01

    Insight of how growth and metabolism in skeletal muscle are related is still lacking in early vertebrates. In this context, molecules involved in these processes, such as leptin, AMP-activated protein kinase (AMPK), target of rapamicyn (TOR), peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α, and oxidative phosphorylation complexes (OXPHOS), were assessed in the skeletal muscle of a fish species. Periods of fasting followed by a period of refeeding were implemented, using the fine flounder as a model (Paralichthys adspersus). This species exhibits remarkably slow growth and food intake, which is linked to an inherent growth hormone (GH) resistance and high circulating levels of leptin. Leptin increased during fasting concomitantly with AMPK activation, which was inversely correlated with TOR activation. On the other hand, AMPK was directly correlated with an increase in PGC-1α and OXPHOS complexes contents. Dramatic changes in the activation and content of these molecules were observed during short-term refeeding. Leptin, AMPK activation, and PGC-1α/OXPHOS complexes contents decreased radically; whereas, TOR activation increased significantly. During long-term refeeding these molecules returned to basal levels. These results suggest that there is a relation among these components; thus, during fasting periods ATP-consuming biosynthetic pathways are repressed and alternative sources of ATP/energy are promoted, a phenomenon that is reversed during anabolic periods. These results provide novel insight on the control of metabolism and growth in the skeletal muscle of a non-mammalian species, suggesting that both processes in fish muscle are closely related and coordinated by a subset of common molecules. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Rac1 Activation Caused by Membrane Translocation of a Guanine Nucleotide Exchange Factor in Akt2-Mediated Insulin Signaling in Mouse Skeletal Muscle.

    Directory of Open Access Journals (Sweden)

    Nobuyuki Takenaka

    Full Text Available Insulin-stimulated glucose uptake in skeletal muscle is mediated by the glucose transporter GLUT4, which is translocated to the plasma membrane following insulin stimulation. Several lines of evidence suggested that the protein kinase Akt2 plays a key role in this insulin action. The small GTPase Rac1 has also been implicated as a regulator of insulin-stimulated GLUT4 translocation, acting downstream of Akt2. However, the mechanisms whereby Akt2 regulates Rac1 activity remain obscure. The guanine nucleotide exchange factor FLJ00068 has been identified as a direct regulator of Rac1 in Akt2-mediated signaling, but its characterization was performed mostly in cultured myoblasts. Here, we provide in vivo evidence that FLJ00068 indeed acts downstream of Akt2 as a Rac1 regulator by using mouse skeletal muscle. Small interfering RNA knockdown of FLJ00068 markedly diminished GLUT4 translocation to the sarcolemma following insulin administration or ectopic expression of a constitutively activated mutant of either phosphoinositide 3-kinase or Akt2. Additionally, insulin and these constitutively activated mutants caused the activation of Rac1 as shown by immunofluorescent microscopy using a polypeptide probe specific to activated Rac1 in isolated gastrocnemius muscle fibers and frozen sections of gastrocnemius muscle. This Rac1 activation was also abrogated by FLJ00068 knockdown. Furthermore, we observed translocation of FLJ00068 to the cell periphery following insulin stimulation in cultured myoblasts. Localization of FLJ00068 in the plasma membrane in insulin-stimulated, but not unstimulated, myoblasts and mouse gastrocnemius muscle was further affirmed by subcellular fractionation and subsequent immunoblotting. Collectively, these results strongly support a critical role of FLJ00068 in Akt2-mediated Rac1 activation in mouse skeletal muscle insulin signaling.

  3. Capillary response to skeletal muscle contraction: evidence that redundancy between vasodilators is physiologically relevant during active hyperaemia.

    Science.gov (United States)

    Lamb, Iain R; Novielli, Nicole M; Murrant, Coral L

    2018-04-15

    The current theory behind matching blood flow to metabolic demand of skeletal muscle suggests redundant interactions between metabolic vasodilators. Capillaries play an important role in blood flow control given their ability to respond to muscle contraction by causing conducted vasodilatation in upstream arterioles that control their perfusion. We sought to determine whether redundancies occur between vasodilators at the level of the capillary by stimulating the capillaries with muscle contraction and vasodilators relevant to muscle contraction. We identified redundancies between potassium and both adenosine and nitric oxide, between nitric oxide and potassium, and between adenosine and both potassium and nitric oxide. During muscle contraction, we demonstrate redundancies between potassium and nitric oxide as well as between potassium and adenosine. Our data show that redundancy is physiologically relevant and involved in the coordination of the vasodilator response during muscle contraction at the level of the capillaries. We sought to determine if redundancy between vasodilators is physiologically relevant during active hyperaemia. As inhibitory interactions between vasodilators are indicative of redundancy, we tested whether vasodilators implicated in mediating active hyperaemia (potassium (K + ), adenosine (ADO) and nitric oxide (NO)) inhibit one another's vasodilatory effects through direct application of pharmacological agents and during muscle contraction. Using the hamster cremaster muscle and intravital microscopy, we locally stimulated capillaries with one vasodilator in the absence and the presence of a second vasodilator (10 -7 m S-nitroso-N-acetylpenicillamine (SNAP), 10 -7 m ADO, 10 mm KCl) applied sequentially and simultaneously, and observed the response in the associated upstream 4A arteriole controlling the perfusion of the stimulated capillary. We found that KCl significantly attenuated SNAP- and ADO-induced vasodilatations by ∼49.7% and

  4. Effect of stage of maturity of grass at harvest on intake, chewing activity and distribution of particle size in faeces from pregnant ewes

    DEFF Research Database (Denmark)

    Jalali, Alireza; Nørgaard, Peder; Weisbjerg, Martin Riis

    2012-01-01

    This study was conducted to investigate the effect of stage of maturity at harvest on the intake of grass silage, eating and ruminating activity and the distribution of faecal particle size in ewes during late pregnancy. A total of 18 Swedish Finull × Dorset 85 ± 8 kg (mean ± s.d.) ewes bearing t...

  5. Population dynamics of the murine lymphokine activated killer system: precursor frequency and kinetics of maturation and renewal.

    Science.gov (United States)

    Owen-Schaub, L B; Hemstreet, G P; Hemingway, L L; Abraham, S R; DeBault, L E

    1987-11-01

    The proliferation kinetics and population renewal of recombinant interleukin-2 (rIL-2)-induced murine lymphokine activated killers (LAK) arising from splenic precursors was studied. Extensive proliferation has been shown to accompany the de novo generation of LAK cytotoxicity. In this report, a thymidine 'hot pulse' suicide technique was employed to examine the sensitivity of LAK progenitors during various time periods following culture initiation. Hot pulse during the first 24 hr of culture resulted in a 30-35% reduction in lytic activity when assayed on day 5. Pulse periods between days 1 and 4 resulted in almost complete inhibition (90-95%) of lytic function when assayed on day 5. Proliferation of LAK progenitors was documented by limiting dilution analysis comparison of splenic precursors and functionally mature LAK cultures. These studies showed a 75- to 80-fold enrichment of LAK progenitors after 3 days culture in rIL-2. By flow cytometric cell cycle analysis, we demonstrated that the number of cells in the S/G2/M phase increased with the length of rIL-2 culture and represented approximately 40% of the cells by day 4. Finally, we used the rate of decay of lytic activity following irradiation as a factor to define the mean life span of a cytotoxic effector in the absence of cellular input. An exponential decrease to approximately 50% of controls was observed within 8-9 hr after irradiation. Taken together, these results suggest that the LAK system is highly dynamic and requires continuous cellular proliferation for its maintenance.

  6. Lifelong physical activity prevents an age-related reduction in arterial and skeletal muscle nitric oxide bioavailability in humans

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Blackwell, James R; Damsgaard, Ramsus

    2012-01-01

    studied the effect of ROS on systemic and skeletal muscle NO bioavailability and leg blood flow by infusion of the antioxidant N-acetylcysteine (NAC). Infusion of NAC increased the bioavailability of NO in OS, as evidenced by an increased concentration of stable metabolites of NO (NOx) in the arterial...

  7. Primary skeletal muscle myoblasts from chronic heart failure patients exhibit loss of anti-inflammatory and proliferative activity

    NARCIS (Netherlands)

    Sente, T.; Berendoncks, A.M. Van; Jonckheere, A.I.; Rodenburg, R.J.T.; Lauwers, P.; Hoof, V. Van; Wouters, A.; Lardon, F.; Hoymans, V.Y.; Vrints, C.J.

    2016-01-01

    BACKGROUND: Peripheral skeletal muscle wasting is a common finding with adverse effects in chronic heart failure (HF). Whereas its clinical relevance is beyond doubt, the underlying pathophysiological mechanisms are not yet fully elucidated. We aimed to introduce and characterize the primary culture

  8. Contraction-induced interleukin-6 gene transcription in skeletal muscle is regulated by c-Jun terminal kinase/activator protein-1.

    Science.gov (United States)

    Whitham, Martin; Chan, M H Stanley; Pal, Martin; Matthews, Vance B; Prelovsek, Oja; Lunke, Sebastian; El-Osta, Assam; Broenneke, Hella; Alber, Jens; Brüning, Jens C; Wunderlich, F Thomas; Lancaster, Graeme I; Febbraio, Mark A

    2012-03-30

    Exercise increases the expression of the prototypical myokine IL-6, but the precise mechanism by which this occurs has yet to be identified. To mimic exercise conditions, C2C12 myotubes were mechanically stimulated via electrical pulse stimulation (EPS). We compared the responses of EPS with the pharmacological Ca(2+) carrier calcimycin (A23187) because contraction induces marked increases in cytosolic Ca(2+) levels or the classical IκB kinase/NFκB inflammatory response elicited by H(2)O(2). We demonstrate that, unlike H(2)O(2)-stimulated increases in IL-6 mRNA, neither calcimycin- nor EPS-induced IL-6 mRNA expression is under the transcriptional control of NFκB. Rather, we show that EPS increased the phosphorylation of JNK and the reporter activity of the downstream transcription factor AP-1. Furthermore, JNK inhibition abolished the EPS-induced increase in IL-6 mRNA and protein expression. Finally, we observed an exercise-induced increase in both JNK phosphorylation and IL-6 mRNA expression in the skeletal muscles of mice after 30 min of treadmill running. Importantly, exercise did not increase IL-6 mRNA expression in skeletal muscle-specific JNK-deficient mice. These data identify a novel contraction-mediated transcriptional regulatory pathway for IL-6 in skeletal muscle.

  9. Activity of Ca(2+,Mg(2+-ATPase of sarcoplasmic reticulum and contraction strength of the frog skeletal muscles under the effect of organophosphorus insecticides

    Directory of Open Access Journals (Sweden)

    D. M. Nozdrenko

    2015-08-01

    Full Text Available The results of an experimental study of organo­phosphorus insecticides, including pirimiphosmethyl, diazinon and chlorpyrifos caused a decline of the contraction properties in m. tibialis anterior fiber bundles of Rana temporaria, as well as sarcoplasmic reticulum Ca2+,Mg2+-ATPase enzymatic activity reduction are outlined in this paper. Concentration-dependent strengths response diminishing in isolated skeletal muscle fiber bundles as a result of non-cholinergic influence of organophosphorus insecticides were found. A decrease of Ca2+,Mg2+-ATPase enzymatic activity in sarcoplasmic reticulum was observed after administration of each insecticide. The most significant inhibition of this enzyme was observed when using chlorpyrifos.

  10. [ACTIVITY OF Ca2+,Mg(2+)-ATPase OF SARCOPLASMIC RETICULUM AND CONTRACTION STRENGTH OF THE FROG SKELETAL MUSCLES UNDER THE EFFECT OF ORGANOPHOSPHORUS INSECTICIDES].

    Science.gov (United States)

    Nozdrenko, D M; Korchinska, L V; Soroca, V M

    2015-01-01

    The results of an experimental study of organophosphorus insecticides, including pirimiphosmethyl, diazinon and chlorpyrifos caused a decline of the contraction properties in m. tibialis anterior fiber bundles of Rana temporaria, as well as sarcoplasmic reticulum Ca2+, Mg(2+)-ATPase enzymatic activity reduction are outlined in this paper. Concentration-dependent strengths response diminishing in isolated skeletal muscle fiber bundles as a result of non-cholinergic influence of organophosphorus insecticides were found. A decrease of Ca2+, Mg(2+)-ATPase enzymatic activity in sarcoplasmic reticulum was observed after administration of each insecticide. The most significant inhibition of this enzyme was observed when using chlorpyrifos.

  11. A longitudinal examination of the influence of maturation on physical self-perceptions and the relationship with physical activity in early adolescent girls.

    Science.gov (United States)

    Knowles, Ann-Marie; Niven, Ailsa G; Fawkner, Samantha G; Henretty, Joan M

    2009-06-01

    This longitudinal study investigated the influence of maturation on physical self-perceptions and the relationship with physical activity in early adolescent girls (N=150; mean age=12.79+/-0.31). Physical characteristics were measured and participants completed the Physical Activity Questionnaire for Children, the Children and Youth Physical Self-Perception Profile and the Pubertal Development Scale on two occasions 12 months apart. The results demonstrated a decrease in overall physical activity levels over 12 months which was not influenced by maturational status or physical characteristics. Additional analysis indicated that physical self-perceptions partially accounted for the explained variance in physical activity change, with physical condition being an important individual predictor of physical activity. Further analysis indicated that body mass was an important individual predictor of changes in perceptions of body attractiveness and physical self-worth. At this age maturation has a limited influence on the physical activity behaviours of early adolescent girls and although the variance in physical activity was partly accounted for by physical self-perceptions, this was a relatively small contribution and other factors related to this drop in physical activity need to be considered longitudinally.

  12. Skeletal muscle insulin resistance associated with cholesterol-induced activation of macrophages is prevented by high density lipoprotein.

    Directory of Open Access Journals (Sweden)

    Andrew L Carey

    Full Text Available BACKGROUND: Emerging evidence suggests that high density lipoprotein (HDL may modulate glucose metabolism through multiple mechanisms including pancreatic insulin secretion as well as insulin-independent glucose uptake into muscle. We hypothesized that HDL may also increase skeletal muscle insulin sensitivity via cholesterol removal and anti-inflammatory actions in macrophages associated with excess adiposity and ectopic lipid deposition. METHODS: Human primary and THP-1 macrophages were treated with vehicle (PBS or acetylated low density lipoprotein (acLDL with or without HDL for 18 hours. Treatments were then removed, and macrophages were incubated with fresh media for 4 hours. This conditioned media was then applied to primary human skeletal myotubes derived from vastus lateralis biopsies taken from patients with type 2 diabetes to examine insulin-stimulated glucose uptake. RESULTS: Conditioned media from acLDL-treated primary and THP-1 macrophages reduced insulin-stimulated glucose uptake in primary human skeletal myotubes compared with vehicle (primary macrophages, 168±21% of basal uptake to 104±19%; THP-1 macrophages, 142±8% of basal uptake to 108±6%; P<0.05. This was restored by co-treatment of macrophages with HDL. While acLDL increased total intracellular cholesterol content, phosphorylation of c-jun N-terminal kinase and secretion of pro- and anti-inflammatory cytokines from macrophages, none were altered by co-incubation with HDL. Insulin-stimulated Akt phosphorylation in human skeletal myotubes exposed to conditioned media was unaltered by either treatment condition. CONCLUSION: Inhibition of insulin-stimulated glucose uptake in primary human skeletal myotubes by conditioned media from macrophages pre-incubated with acLDL was restored by co-treatment with HDL. However, these actions were not linked to modulation of common pro- or anti-inflammatory mediators or insulin signaling via Akt.

  13. Supplementation of Magnolol Attenuates Skeletal Muscle Atrophy in Bladder Cancer-Bearing Mice Undergoing Chemotherapy via Suppression of FoxO3 Activation and Induction of IGF-1.

    Directory of Open Access Journals (Sweden)

    Meng-Chuan Chen

    Full Text Available Skeletal muscle atrophy, the most prominent phenotypic feature of cancer cachexia, is often observed in cancer patients undergoing chemotherapy. Magnolol (M extracted from Magnolia officinalis exhibits several pharmacological effects including anti-inflammatory and anticancer activities. In this study, we investigated whether magnolol supplementation protects against the development of cachexia symptoms in bladder cancer-bearing mice undergoing chemotherapy. Combined treatment of magnolol with chemotherapeutic drugs, such as gemcitabine and cisplatin (TGCM or gemcitabine (TGM, markedly attenuates the body weight loss and skeletal muscle atrophy compared with conventional chemotherapy (TGC. The antiatrophic effect of magnolol may be associated with inhibition of myostatin and activin A formation, as well as FoxO3 transcriptional activity resulting from Akt activation, thereby suppressing ubiquitin ligases MuRF-1 and MAFbx/atrogin-1 expression, as well as proteasomal enzyme activity. Notably, magnolol-induced insulin-like growth factor 1 (IGF-1 production and related protein synthesis may also contribute to its protective effects. The decreased food intake, and intestinal injury and dysfunction observed in the mice of TGC group were significantly improved in the TGCM and TGM groups. Moreover, the increased inflammatory responses evidenced by elevation of proinflammatory cytokine formation and NF-κB activation occurred in the atrophying muscle of TGC group were markedly inhibited in mice of combined treatment with magnolol. In summary, these findings support that magnolol is a promising chemopreventive supplement for preventing chemotherapy-induced skeletal muscle atrophy associated with cancer cachexia by suppressing muscle protein degradation, and inflammatory responses, as well as increasing IGF-1-mediated protein synthesis.

  14. Contractile Activity Is Necessary to Trigger Intermittent Hypobaric Hypoxia-Induced Fiber Size and Vascular Adaptations in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    David Rizo-Roca

    2018-05-01

    Full Text Available Altitude training has become increasingly popular in recent decades. Its central and peripheral effects are well-described; however, few studies have analyzed the effects of intermittent hypobaric hypoxia (IHH alone on skeletal muscle morphofunctionality. Here, we studied the effects of IHH on different myofiber morphofunctional parameters, investigating whether contractile activity is required to elicit hypoxia-induced adaptations in trained rats. Eighteen male Sprague-Dawley rats were trained 1 month and then divided into three groups: (1 rats in normobaria (trained normobaric inactive, TNI; (2 rats subjected daily to a 4-h exposure to hypobaric hypoxia equivalent to 4,000 m (trained hypobaric inactive, THI; and (3 rats subjected daily to a 4-h exposure to hypobaric hypoxia just before performing light exercise (trained hypobaric active, THA. After 2 weeks, the tibialis anterior muscle (TA was excised. Muscle cross-sections were stained for: (1 succinate dehydrogenase to identify oxidative metabolism; (2 myosin-ATPase to identify slow- and fast-twitch fibers; and (3 endothelial-ATPase to stain capillaries. Fibers were classified as slow oxidative (SO, fast oxidative glycolytic (FOG, fast intermediate glycolytic (FIG or fast glycolytic (FG and the following parameters were measured: fiber cross-sectional area (FCSA, number of capillaries per fiber (NCF, NCF per 1,000 μm2 of FCSA (CCA, fiber and capillary density (FD and CD, and the ratio between CD and FD (C/F. THI rats did not exhibit significant changes in most of the parameters, while THA animals showed reduced fiber size. Compared to TNI rats, FOG fibers from the lateral/medial fields, as well as FIG and FG fibers from the lateral region, had smaller FCSA in THA rats. Moreover, THA rats had increased NCF in FG fibers from all fields, in medial and posterior FIG fibers and in posterior FOG fibers. All fiber types from the three analyzed regions (except the posterior FG fibers displayed a

  15. Quantitative Assessment of Cervical Vertebral Maturation Using Cone Beam Computed Tomography in Korean Girls

    OpenAIRE

    Byun, Bo-Ram; Kim, Yong-Il; Yamaguchi, Tetsutaro; Maki, Koutaro; Son, Woo-Sung

    2015-01-01

    This study was aimed to examine the correlation between skeletal maturation status and parameters from the odontoid process/body of the second vertebra and the bodies of third and fourth cervical vertebrae and simultaneously build multiple regression models to be able to estimate skeletal maturation status in Korean girls. Hand-wrist radiographs and cone beam computed tomography (CBCT) images were obtained from 74 Korean girls (6?18 years of age). CBCT-generated cervical vertebral maturation ...

  16. Na+-K+-ATPase in rat skeletal muscle: muscle fiber-specific differences in exercise-induced changes in ion affinity and maximal activity

    DEFF Research Database (Denmark)

    Juel, Carsten

    2008-01-01

    It is unclear whether muscle activity reduces or increases Na(+)-K(+)-ATPase maximal in vitro activity in rat skeletal muscle, and it is not known whether muscle activity changes the Na(+)-K(+)-ATPase ion affinity. The present study uses quantification of ATP hydrolysis to characterize muscle fiber...... membranes of glycolytic muscle, which abolished the fiber-type difference in Na(+) affinity. K(m) for K(+) (in the presence of Na(+)) was not influenced by running. Running only increased the maximal in vitro activity (V(max)) in total membranes from soleus, whereas V(max) remained constant in the three...... other muscles tested. In conclusion, muscle activity induces fiber type-specific changes both in Na(+) affinity and maximal in vitro activity of the Na(+)-K(+)-ATPase. The underlying mechanisms may involve translocation of subunits and increased association between PLM units and the alphabeta complex...

  17. Ginsenoside Rb1 improves postoperative fatigue syndrome by reducing skeletal muscle oxidative stress through activation of the PI3K/Akt/Nrf2 pathway in aged rats.

    Science.gov (United States)

    Zhuang, Cheng-Le; Mao, Xiang-Yu; Liu, Shu; Chen, Wei-Zhe; Huang, Dong-Dong; Zhang, Chang-Jing; Chen, Bi-Cheng; Shen, Xian; Yu, Zhen

    2014-10-05

    Ginsenoside Rb1 is reported to possess anti-fatigue activity, but the mechanisms remain unknown. The aim of this study was to investigate the molecular mechanisms responsible for the anti-fatigue effect of ginsenoside Rb1 on postoperative fatigue syndrome induced by major small intestinal resection (MSIR) in aged rat. Aged rats with MSIR were administrated with ginsenoside Rb1 (15 mg/kg) once a day from 3 days before surgery to the day of sacrifice, or with saline as corresponding controls. Rats without MSIR but going through the same surgery procedure were administrated with saline as blank controls. Anti-fatigue effect was assessed by an open field test; superoxide dismutase, reactive oxygen species and malondialdehyde in skeletal muscle were determined. The mRNA levels of Akt2 and Nrf2 in skeletal muscle were measured by real-time quantitative PCR. The activation of Akt and Nrf2 was examined by western blot and immunohistofluorescence. Our results revealed that ginsenoside Rb1 significantly increased the journey and the rearing frequency, decreased the time of rest in aged rats with MSIR. In addition, ginsenoside Rb1 significantly reduced reactive oxygen species and malondialdehyde release and increased the superoxide dismutase activity of skeletal muscle in aged rats with MSIR. Ginsenoside Rb1 also increased the expression of Akt2 and Nrf2 mRNA, up-regulated Akt phosphorylation and Nrf2 nuclear translocation. These findings indicate that ginsenoside Rb1 has an anti-fatigue effect on postoperative fatigue syndrome in aged rat, and the mechanism possibly involves activation of the PI3K/Akt pathway with subsequent Nrf2 nuclear translocation and induction of antioxidant enzymes. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. An extract of Artemisia dracunculus L. inhibits ubiquitin-proteasome activity and preserves skeletal muscle mass in a murine model of diabetes.

    Directory of Open Access Journals (Sweden)

    Heather Kirk-Ballard

    Full Text Available Impaired insulin signaling is a key feature of type 2 diabetes and is associated with increased ubiquitin-proteasome-dependent protein degradation in skeletal muscle. An extract of Artemisia dracunculus L. (termed PMI5011 improves insulin action by increasing insulin signaling in skeletal muscle. We sought to determine if the effect of PMI5011 on insulin signaling extends to regulation of the ubiquitin-proteasome system. C2C12 myotubes and the KK-A(y murine model of type 2 diabetes were used to evaluate the effect of PMI5011 on steady-state levels of ubiquitylation, proteasome activity and expression of Atrogin-1 and MuRF-1, muscle-specific ubiquitin ligases that are upregulated with impaired insulin signaling. Our results show that PMI5011 inhibits proteasome activity and steady-state ubiquitylation levels in vitro and in vivo. The effect of PMI5011 is mediated by PI3K/Akt signaling and correlates with decreased expression of Atrogin-1 and MuRF-1. Under in vitro conditions of hormonal or fatty acid-induced insulin resistance, PMI5011 improves insulin signaling and reduces Atrogin-1 and MuRF-1 protein levels. In the KK-A(y murine model of type 2 diabetes, skeletal muscle ubiquitylation and proteasome activity is inhibited and Atrogin-1 and MuRF-1 expression is decreased by PMI5011. PMI5011-mediated changes in the ubiquitin-proteasome system in vivo correlate with increased phosphorylation of Akt and FoxO3a and increased myofiber size. The changes in Atrogin-1 and MuRF-1 expression, ubiquitin-proteasome activity and myofiber size modulated by PMI5011 in the presence of insulin resistance indicate the botanical extract PMI5011 may have therapeutic potential in the preservation of muscle mass in type 2 diabetes.

  19. Alternate-Day High-Fat Diet Induces an Increase in Mitochondrial Enzyme Activities and Protein Content in Rat Skeletal Muscle.

    Science.gov (United States)

    Li, Xi; Higashida, Kazuhiko; Kawamura, Takuji; Higuchi, Mitsuru

    2016-04-06

    Long-term high-fat diet increases muscle mitochondrial enzyme activity and endurance performance. However, excessive calorie intake causes intra-abdominal fat accumulation and metabolic syndrome. The purpose of this study was to investigate the effect of an alternating day high-fat diet on muscle mitochondrial enzyme activities, protein content, and intra-abdominal fat mass in rats. Male Wistar rats were given a standard chow diet (CON), high-fat diet (HFD), or alternate-day high-fat diet (ALT) for 4 weeks. Rats in the ALT group were fed a high-fat diet and standard chow every other day for 4 weeks. After the dietary intervention, mitochondrial enzyme activities and protein content in skeletal muscle were measured. Although body weight did not differ among groups, the epididymal fat mass in the HFD group was higher than those of the CON and ALT groups. Citrate synthase and beta-hydroxyacyl CoA dehydrogenase activities in the plantaris muscle of rats in HFD and ALT were significantly higher than that in CON rats, whereas there was no difference between HFD and ALT groups. No significant difference was observed in muscle glycogen concentration or glucose transporter-4 protein content among the three groups. These results suggest that an alternate-day high-fat diet induces increases in mitochondrial enzyme activities and protein content in rat skeletal muscle without intra-abdominal fat accumulation.

  20. Unexplored antifungal activity of linear battacin lipopeptides against planktonic and mature biofilms of C. albicans.

    Science.gov (United States)

    De Zoysa, Gayan Heruka; Glossop, Hugh Douglas; Sarojini, Vijayalekshmi

    2018-02-25

    Novel antifungal agents are required against pathogenic fungi such as Candida albicans. We report the anticandidal activity of battacin lipopeptide antibiotics with previously unexplored antifungal activity. From amongst sixteen battacin lipopeptides tested against C. alibicans (SC5314) the 4-methyl hexanoyl conjugated trimeric lipopeptide 13 emerged as the lead candidate with a MIC of 6.25 μM and negligible haemolysis of mouse red blood cells. The potency of this lipopeptide was maintained under acidic conditions. Additionally, antifungal activity was further enhanced with amphotericin B at its non-haemolytic concentrations. Herein we have demonstrated for the first time that battacin lipopeptides prevent C. albicans biofilm colonisation as well as inhibit pre-formed biofilms of this fungal pathogen. XTT biofilm assays revealed that 13 prevented colonisation of C. albicans biofilms at its MIC (6.25 μM) and, at a higher concentration, eradicated 24 h (25 μM) and 48 h (62.5 μM) old preformed biofilms. In comparison, we found that amphotericin at much lower concentrations prevented biofilm colonisation (0.78 μM) and inhibited 24 h old preformed biofilms (6.25 μM), however was completely inactive against 48 h old preformed biofilms. Thus, lipopeptide 13 is more effective than amphotericin at eradicating more mature C. albicans biofilms. The membrane lytic mechanism of action of compound 13 was validated by a colorimetric assay using lipid vesicles mimicking fungal membranes in which compound 13 effected an immediate dark purple to red colour transition of suspended vesicles upon peptide interaction. In addition, TEM images of C. albicans cells exposed to 13 showed clearly disrupted cellular membranes. Interestingly, compound 13 increased the endogenous generation of reactive oxygen species (ROS) in a concentration dependent manner. In the presence of an antioxidant, ascorbic acid, ROS production was diminished yet antifungal activity

  1. Computational radiology in skeletal radiography

    International Nuclear Information System (INIS)

    Peloschek, Ph.; Nemec, S.; Widhalm, P.; Donner, R.; Birngruber, E.; Thodberg, H.H.; Kainberger, F.; Langs, G.

    2009-01-01

    Recent years have brought rapid developments in computational image analysis in musculo-skeletal radiology. Meanwhile the algorithms have reached a maturity that makes initial clinical use feasible. Applications range from joint space measurement to erosion quantification, and from fracture detection to the assessment of alignment angles. Current results of computational image analysis in radiography are very promising, but some fundamental issues remain to be clarified, among which the definition of the optimal trade off between automatization and operator-dependency, the integration of these tools into clinical work flow and last not least the proof of incremental clinical benefit of these methods.

  2. Beyond maturity

    International Nuclear Information System (INIS)

    Tessmer, W.B.

    1990-01-01

    The Nuclear Power Plant Simulator Industry has undergone to decades of evolution in experience, technology and business practices. Link-Miles Simulation Corporation (LMSC) has been contracted to build 68 Full Scope Nuclear Simulators during the 1970's and 1980's. Traditional approaches to design, development and testing have been used to satisfy specifications for initial customer requirements. However, the Industry has matured. All U.S. Nuclear Utilities own, or have under contract, at least one simulator. Other industrial nations have centralized training facilities to satisfy the simulator training needs. The customer of the future is knowledgeable and experienced in the development and service of nuclear simulators. The role of the simulator vendor is changing in order to alter the traditional approach for development. Covenants between the vendors and their customers solidify new complementary roles. This paper presents examples of current simulator project development with recommendations for future endeavors

  3. A marked animal-vegetal polarity in the localization of Na(+),K(+) -ATPase activity and its down-regulation following progesterone-induced maturation.

    Science.gov (United States)

    Mohanty, Basant Kumar; Gupta, Brij L

    2012-02-01

    The stage-VI Xenopus oocyte has a very distinct animal-vegetal polarity with structural and functional asymmetry. In this study, we show the expression and distribution pattern of Na(+),K(+) -ATPase in stage-VI oocytes, and its changes following progesterone-induced maturation. Using enzyme-specific electron microscopy phosphatase histochemistry, [(3) H]-ouabain autoradiography, and immunofluorescence cytochemistry at light microscopic level, we find that Na(+),K(+) -ATPase activity is mainly confined to the animal hemisphere. Electron microscopy histochemical results also suggest that polarized distribution of Na(+),K(+) -ATPase activity persists following progesterone-induced maturation, and it becomes gradually more polarized towards the animal pole. The time course following progesterone-induced maturation suggests that there is an initial up-regulation and then gradual down-regulation of Na(+),K(+) -ATPase activity leading to germinal vesicle breakdown (GVBD). By GVBD, the Na(+),K(+) -ATPase activity is completely down-regulated due to endocytotic removal of pump molecules from the plasma membrane into the sub-cortical region of the oocyte. This study provides the first direct evidence for a marked asymmetric localization of Na(+),K(+) -ATPase activity in any vertebrate oocyte. Here, we propose that such asymmetry in Na(+),K(+) -ATPase activity in stage-VI oocytes, and their down-regulation following progesterone-induced maturation, is likely to have a role in the active state of the germinal vesicle in stage-VI oocytes and chromosomal condensation after GVBD. Copyright © 2011 Wiley Periodicals, Inc.

  4. How to make a tree ring: Coupling stem water flow and cambial activity in mature Alpine conifers

    Science.gov (United States)

    Peters, Richard L.; Frank, David C.; Treydte, Kerstin; Steppe, Kathy; Kahmen, Ansgar; Fonti, Patrick

    2017-04-01

    Inter-annual tree-ring measurements are used to understand tree-growth responses to climatic variability and reconstruct past climate conditions. In parallel, mechanistic models use experimentally defined plant-atmosphere interactions to explain past growth responses and predict future environmental impact on forest productivity. Yet, substantial inconsistencies within mechanistic model ensembles and mismatches with empirical data indicate that significant progress is still needed to understand the processes occurring at an intra-annual resolution that drive annual growth. However, challenges arise due to i) few datasets describing climatic responses of high-resolution physiological processes over longer time-scales, ii) uncertainties on the main mechanistic process limiting radial stem growth and iii) complex interactions between multiple environmental factors which obscure detection of the main stem growth driver, generating a gap between our understanding of intra- and inter-annual growth mechanisms. We attempt to bridge the gap between inter-annual tree-ring width and sub-daily radial stem-growth and provide a mechanistic perspective on how environmental conditions affect physiological processes that shape tree rings in conifers. We combine sub-hourly sap flow and point dendrometer measurements performed on mature Alpine conifers (Larix decidua) into an individual-based mechanistic tree-growth model to simulate sub-hourly cambial activity. The monitored trees are located along a high elevational transect in the Swiss Alps (Lötschental) to analyse the effect of increasing temperature. The model quantifies internal tree hydraulic pathways that regulate the turgidity within the cambial zone and induce cell enlargement for radial growth. The simulations are validated against intra-annual growth patterns derived from xylogenesis data and anatomical analyses. Our efforts advance the process-based understanding of how climate shapes the annual tree-ring structures

  5. Comparison of total phenolic content, scavenging activity and HPLC-ESI-MS/MS profiles of both young and mature leaves and stems of Andrographis paniculata.

    Science.gov (United States)

    Chua, Lee Suan; Yap, Ken Choy; Jaganath, Indu Bala

    2013-12-01

    The total phenolic content and radical scavenging activity of Andrographis paniculata has been investigated to estimate the amount of phenolic compounds and diterpene lactones, respectively in the plant extracts. The stem extracts exhibited higher total phenolic content and scavenging activity than those of the leaf extracts from both young and mature plants. A range of 19.6-47.8 mg extract of A. paniculata from different parts of the plant is equivalent to the scavenging activity exhibited by one mg of standard Trolox. HPLC-ESI-MS/MS was also used to identify simultaneously the phytochemicals from the leaves and stems of both young and mature plant samples. Of the identified compounds, seven of the sixteen diterpene lactones, three of the six flavonoids, five of the six phenolic acids and two cyclic acids are reported here for the first time for this species. Multivariate statistical approaches such as Hierarchiral Component Analysis (HCA) and Principle Component Analysis (PCA) have clustered the plant extracts into the leaf and stem groups, regardless of plant age. Further classification based on the phytochemical profiles revealed that mostly phenolic acids and flavonoids were from the young leaf extracts, and diterpenoids and their glycosides from the mature leaf extracts. However, the phytochemical profiles for the stems of both young and mature plants were not significantly different as presented in the dendrogram of HCA and the score plot of PCA. The marker for mature plants might be the m/z 557 ion (dihydroxyl dimethyl 19-[(beta-D-glucopyranosyl)oxy]-19-oxo-ent-labda-8(17),13-dien-16,15-olide), whereas the m/z 521 ion (propyl neoandrographolide) could be the marker for leaf extracts.

  6. Regulation of skeletal muscle mitochondrial activity by thyroid hormones: focus on "old" triiodothyronine and the "emerging" 3,5-diiodothyronine".

    OpenAIRE

    Assunta eLombardi; Maria eMoreno; Pieter eDe Lange; Susanna eIossa; Rosa Anna eBusiello; Fernando eGoglia

    2015-01-01

    3,5,3'-triiodo-L-thyronine (T3) plays a crucial role in regulating metabolic rate and fuel oxidation; however, the mechanisms by which it affects whole-body energy metabolism are still not completely understood. Skeletal muscle (SKM) plays a relevant role in energy metabolism and responds to thyroid state by remodeling the metabolic characteristics and cytoarchitecture of myocytes. These processes are coordinated with changes in mitochondrial content, bioenergetics, substrate oxidation rate, ...

  7. Depression of voltage-activated Ca2+ release in skeletal muscle by activation of a voltage-sensing phosphatase.

    Science.gov (United States)

    Berthier, Christine; Kutchukian, Candice; Bouvard, Clément; Okamura, Yasushi; Jacquemond, Vincent

    2015-04-01

    Phosphoinositides act as signaling molecules in numerous cellular transduction processes, and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) regulates the function of several types of plasma membrane ion channels. We investigated the potential role of PtdIns(4,5)P2 in Ca(2+) homeostasis and excitation-contraction (E-C) coupling of mouse muscle fibers using in vivo expression of the voltage-sensing phosphatases (VSPs) Ciona intestinalis VSP (Ci-VSP) or Danio rerio VSP (Dr-VSP). Confocal images of enhanced green fluorescent protein-tagged Dr-VSP revealed a banded pattern consistent with VSP localization within the transverse tubule membrane. Rhod-2 Ca(2+) transients generated by 0.5-s-long voltage-clamp depolarizing pulses sufficient to elicit Ca(2+) release from the sarcoplasmic reticulum (SR) but below the range at which VSPs are activated were unaffected by the presence of the VSPs. However, in Ci-VSP-expressing fibers challenged by 5-s-long depolarizing pulses, the Ca(2+) level late in the pulse (3 s after initiation) was significantly lower at 120 mV than at 20 mV. Furthermore, Ci-VSP-expressing fibers showed a reversible depression of Ca(2+) release during trains, with the peak Ca(2+) transient being reduced by ∼30% after the application of 10 200-ms-long pulses to 100 mV. A similar depression was observed in Dr-VSP-expressing fibers. Cav1.1 Ca(2+) channel-mediated current was unaffected by Ci-VSP activation. In fibers expressing Ci-VSP and a pleckstrin homology domain fused with monomeric red fluorescent protein (PLCδ1PH-mRFP), depolarizing pulses elicited transient changes in mRFP fluorescence consistent with release of transverse tubule-bound PLCδ1PH domain into the cytosol; the voltage sensitivity of these changes was consistent with that of Ci-VSP activation, and recovery occurred with a time constant in the 10-s range. Our results indicate that the PtdIns(4,5)P2 level is tightly maintained in the transverse tubule membrane of the muscle fibers

  8. Correlation between Dental Maturation and Chronological Age in Patients with Cerebral Palsy, Mental Retardation, and Down Syndrome

    Science.gov (United States)

    Diz, P.; Limeres, J.; Salgado, A. F. P.; Tomas, I.; Delgado, L. F.; Vazquez, E.; Feijoo, J. F.

    2011-01-01

    Determining a child's chronological age and stage of maturation is particularly important in fields such as paediatrics, orthopaedics, and orthodontics, as well as in forensic and anthropological studies. Some systemic conditions can cause abnormal physiological maturation, and skeletal maturation is usually more delayed than dental maturation.…

  9. Impaired insulin activation and dephosphorylation of glycogen synthase in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Højlund, Kurt; Andersen, Nicoline Resen

    2008-01-01

    CONTEXT: Insulin resistance is a major risk factor for type 2 diabetes in women with polycystic ovary syndrome (PCOS). The molecular mechanisms underlying reduced insulin-mediated glycogen synthesis in skeletal muscle of patients with PCOS have not been established. SUBJECTS AND METHODS: We...... metabolically characterized by euglycemic-hyperinsulinemic clamps and indirect calorimetry. RESULTS: Reduced insulin-mediated glucose disposal (P .... No significant abnormalities in GSK-3alpha or -3beta were found in PCOS subjects. Pioglitazone treatment improved insulin-stimulated glucose metabolism and GS activity in PCOS (all P

  10. The effects of beta-adrenoceptor activation on contraction in isolated fast- and slow-twitch skeletal muscle fibres of the rat.

    OpenAIRE

    Cairns, S. P.; Dulhunty, A. F.

    1993-01-01

    1. The aim of the experiments was to examined the effects of beta-adrenoceptor activation on twitch and tetanic contractions in fast- and slow-twitch mammalian skeletal muscle fibres. Isometric force was recorded from bundles of intact fibres isolated from the normal and denervated slow-twitch soleus and normal fast-twitch sternomastoid muscles of the rat. 2. Terbutaline (10 microM), a beta 2-adrenoceptor agonist, induced an average 15% potentiation of peak twitch and peak tetanic force in no...

  11. The influence of gamma radiation on catheptic activity and on ultrastructure of lysosomes and postmortem skeletal muscle of poultry Gallus domesticus

    International Nuclear Information System (INIS)

    Ali, Mumtaz.

    1975-01-01

    A three-part study is presented dealing with radiation-induced release of cathepsins from isolated lysosomes, irradiation inactivation of cathepsins, and ultrastructural changes in irradiated lysosomes and skeletal muscle. After chicken liver lysosomes were irradiated with 0.1 to 1.0 Mrad of gamma radiation a decrease in absorbance at 540 nm of lysosomal suspensions and an increase of free enzyme activity due to a release of cathepsins were noted. Examination of irradiated isolated lysosomes by electron microscopy showed leakage of material from weak points in the lysosomal membrane. Examination of irradiated chicken pectoralis muscle revealed an increase in interfibrillar spaces and some breaks in the myofibres. (LL)

  12. Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype

    DEFF Research Database (Denmark)

    Martinat, Cecile; Bacci, Jean-Jacques; Leete, Thomas

    2006-01-01

    's disease. We sought to identify genes that can potentiate maturation of ES cell cultures to the midbrain DA neuron phenotype. A number of transcription factors have been implicated in the development of midbrain DA neurons by expression analyses and loss-of-function knockout mouse studies, including Nurr1......Midbrain dopamine (DA) neurons play a central role in the regulation of voluntary movement, and their degeneration is associated with Parkinson's disease. Cell replacement therapies, and in particular embryonic stem (ES) cell-derived DA neurons, offer a potential therapeutic venue for Parkinson......, Pitx3, Lmx1b, Engrailed-1, and Engrailed-2. However, none of these factors appear sufficient alone to induce the mature midbrain DA neuron phenotype in ES cell cultures in vitro, suggesting a more complex regulatory network. Here we show that Nurr1 and Pitx3 cooperatively promote terminal maturation...

  13. The influences of inoculants from municipal sludge and solid waste on compost stability, maturity and enzyme activities during chicken manure composting.

    Science.gov (United States)

    Li, Shuyan; Li, Jijin; Yuan, Jing; Li, Guoxue; Zang, Bing; Li, Yangyang

    2017-07-01

    The aim of this study was to investigate the influence of inoculants on compost stability, maturity and enzyme activities during composting of chicken manure and cornstalk. Two microbial inoculants (originated from aerobic municipal sludge and municipal solid waste, respectively) were used in composting at the rate of 0.3% of initial raw materials (wet weight). No microbial inoculums were added to the control. The experiment was conducted under aerobic conditions for 53 days. The results show that enzyme activity is an important index to comprehensively evaluate the composting stability and maturity. Microbes originated from sludge works best in terms of composting stability and maturity (C:N ratio decreased from 15.5 to 10, and germination index increased to 109%). Microbial inoculums originated from sludge and municipal solid waste extended the time of thermophilic phase for 11 and 7 days, respectively. Microbial inoculums originated from sludge and MSW significantly increased the average of catalase activity (by 15.0% and 12.1%, respectively), urease activity (by 21.5% and 12.2%, respectively) and cellulase activity (by 32.1% and 26.1%, respectively) during composting.

  14. AMP-activated protein kinase plays an important evolutionary conserved role in the regulation of glucose metabolism in fish skeletal muscle cells.

    Directory of Open Access Journals (Sweden)

    Leonardo J Magnoni

    Full Text Available AMPK, a master metabolic switch, mediates the observed increase of glucose uptake in locomotory muscle of mammals during exercise. AMPK is activated by changes in the intracellular AMP:ATP ratio when ATP consumption is stimulated by contractile activity but also by AICAR and metformin, compounds that increase glucose transport in mammalian muscle cells. However, the possible role of AMPK in the regulation of glucose metabolism in skeletal muscle has not been investigated in other vertebrates, including fish. In this study, we investigated the effects of AMPK activators on glucose uptake, AMPK activity, cell surface levels of trout GLUT4 and expression of GLUT1 and GLUT4 as well as the expression of enzymes regulating glucose disposal and PGC1α in trout myotubes derived from a primary muscle cell culture. We show that AICAR and metformin significantly stimulated glucose uptake (1.6 and 1.3 fold, respectively and that Compound C completely abrogated the stimulatory effects of the AMPK activators on glucose uptake. The combination of insulin and AMPK activators did not result in additive nor synergistic effects on glucose uptake. Moreover, exposure of trout myotubes to AICAR and metformin resulted in an increase in AMPK activity (3.8 and 3 fold, respectively. We also provide evidence suggesting that stimulation of glucose uptake by AMPK activators in trout myotubes may take place, at least in part, by increasing the cell surface and mRNA levels of trout GLUT4. Finally, AICAR increased the mRNA levels of genes involved in glucose disposal (hexokinase, 6-phosphofructokinase, pyruvate kinase and citrate synthase and mitochondrial biogenesis (PGC-1α and did not affect glycogen content or glycogen synthase mRNA levels in trout myotubes. Therefore, we provide evidence, for the first time in non-mammalian vertebrates, suggesting a potentially important role of AMPK in stimulating glucose uptake and utilization in the skeletal muscle of fish.

  15. Influence of low dose irradiation on differentiation, maturation and T-cell activation of human dendritic cells

    Energy Technology Data Exchange (ETDEWEB)

    Jahns, Jutta [Department of Radiotherapy and Radiation Oncology, University of Leipzig, Stephanstrasse 21, 04103 Leipzig (Germany); Anderegg, Ulf; Saalbach, Anja [Department for Dermatology, Venerology and Allergology, University of Leipzig, Johannisallee 30, 04103 Leipzig (Germany); Rosin, Britt; Patties, Ina; Glasow, Annegret [Department of Radiotherapy and Radiation Oncology, University of Leipzig, Stephanstrasse 21, 04103 Leipzig (Germany); Kamprad, Manja [Institute for Clinical Immunology and Transfusion Medicine, University of Leipzig, Johannisallee 30, 04103 Leipzig (Germany); Scholz, Markus [Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Haertelstr. 16-18, 04103 Leipzig (Germany); Hildebrandt, Guido, E-mail: Guido.Hildebrandt@uni-rostock.de [Department of Radiotherapy and Radiation Oncology, University of Rostock, Suedring 75, 18059 Rostock (Germany); Department of Radiotherapy and Radiation Oncology, University of Leipzig, Stephanstrasse 21, 04103 Leipzig (Germany)

    2011-05-10

    Ionizing irradiation could act directly on immune cells and may induce bystander effects mediated by soluble factors that are released by the irradiated cells. This is the first study analyzing both the direct effect of low dose ionizing radiation (LDIR) on the maturation and cytokine release of human dendritic cells (DCs) and the functional consequences for co-cultured T-cells. We showed that irradiation of DC-precursors in vitro does not influence surface marker expression or cytokine profile of immature DCs nor of mature DCs after LPS treatment. There was no difference of single dose irradiation versus fractionated irradiation protocols on the behavior of the mature DCs. Further, the low dose irradiation did not change the capacity of the DCs to stimulate T-cell proliferation. But the irradiation of the co-culture of DCs and T-cells revealed significantly lower proliferation of T-cells with higher doses. Summarizing the data from approx. 50 DC preparations there is no significant effect of low dose ionizing irradiation on the cytokine profile, surface marker expression and maturation of DCs in vitro although functional consequences cannot be excluded.

  16. Fine-structural distribution of MMP-2 and MMP-9 activities in the rat skeletal muscle upon training: a study by high-resolution in situ zymography.

    Science.gov (United States)

    Yeghiazaryan, Marine; Żybura-Broda, Katarzyna; Cabaj, Anna; Włodarczyk, Jakub; Sławińska, Urszula; Rylski, Marcin; Wilczyński, Grzegorz M

    2012-07-01

    Matrix metalloproteinases (MMPs) are key regulators of extracellular matrix remodeling, but have also important intracellular targets. The purpose of this study was to examine the activity and subcellular localization of the gelatinases MMP-2 and MMP-9 in skeletal muscle of control and physically trained rats. In control hind limb muscle, the activity of the gelatinases was barely detectable. In contrast, after 5 days of intense exercise, in Soleus (Sol), but not Extensor digitorum longus (EDL) muscle, significant upregulation of gelatinolytic activity in myofibers was observed mainly in the nuclei, as assessed by high resolution in situ zymography. The nuclei of quiescent satellite cells did not contain the activity. Within the myonuclei, the gelatinolytic activity colocalized with an activated RNA Polymerase II. Also in Sol, but not in EDL, there were few foci of mononuclear cells with strongly positive cytoplasm, associated with apparent necrotic myofibers. These cells were identified as activated satellite cells/myoblasts. No extracellular gelatinase activity was observed. Gel zymography combined with subcellular fractionation revealed training-related upregulation of active MMP-2 in the nuclear fraction, and increase of active MMP-9 in the cytoplasmic fraction of Sol. Using RT-PCR, selective increase in MMP-9 mRNA was observed. We conclude that training activates nuclear MMP-2, and increases expression and activity of cytoplasmic MMP-9 in Sol, but not in EDL. Our results suggest that the gelatinases are involved in muscle adaptation to training, and that MMP-2 may play a novel role in myonuclear functions.

  17. Comparison of multiple transcriptomes exposes unified and divergent features of quiescent and activated skeletal muscle stem cells

    DEFF Research Database (Denmark)

    Pietrosemoli, Natalia; Mella, Sébastien; Yennek, Siham

    2017-01-01

    of identifying quiescent markers. Here, we focused on the quiescent cell state and generated new transcriptome profiles that include subfractionations of adult satellite cell populations, and an artificially induced prenatal quiescent state, to identify core signatures for quiescent and proliferating. Methods......Background: Skeletal muscle satellite (stem) cells are quiescent in adult mice and can undergo multiple rounds of proliferation and self-renewal following muscle injury. Several labs have profiled transcripts of myogenic cells during the developmental and adult myogenesis with the aim...... with true in vivo quiescence from those that are first responding genes due to disruption of the stem cell niche....

  18. Factors Associated with the Serum Myostatin Level in Patients Undergoing Peritoneal Dialysis: Potential Effects of Skeletal Muscle Mass and Vitamin D Receptor Activator Use.

    Science.gov (United States)

    Yamada, Shunsuke; Tsuruya, Kazuhiko; Yoshida, Hisako; Tokumoto, Masanori; Ueki, Kenji; Ooboshi, Hiroaki; Kitazono, Takanari

    2016-07-01

    Myostatin is a member of the transforming growth factor-β family, which regulates synthesis and degradation of skeletal muscle proteins and is associated with the development of sarcopenia. It is up-regulated in the skeletal muscle of chronic kidney disease patients and is considered to be involved in the development of uremic sarcopenia. However, serum myostatin levels have rarely been determined, and the relationship between serum myostatin levels with clinical and metabolic factors remains unknown. This cross-sectional study investigated the association between serum myostatin level and clinical factors in 69 outpatients undergoing peritoneal dialysis. Serum myostatin level was determined by commercially available enzyme-linked immunosorbent assay (ELISA). Univariable and multivariable analysis were conducted to determine factors associated with serum myostatin levels. The factors included age, sex, diabetes mellitus, dialysis history, body mass index, residual kidney function, peritoneal dialysate volume, serum biochemistries, and the use of vitamin D receptor activators (VDRAs). Mean serum myostatin level was 7.59 ± 3.37 ng/mL. There was no association between serum myostatin level and residual kidney function. Serum myostatin levels were significantly and positively associated with lean body mass measured by the creatinine kinetic method and negatively associated with the use of VDRAs after adjustment for potential confounding factors. Our study indicated that serum myostatin levels are associated with skeletal muscle mass and are lower in patients treated with VDRAs. Further studies are necessary to determine the significance of measuring serum myostatin level in patients undergoing peritoneal dialysis.

  19. Telmisartan ameliorates insulin sensitivity by activating the AMPK/SIRT1 pathway in skeletal muscle of obese db/db mice

    Directory of Open Access Journals (Sweden)

    Shiota Asuka

    2012-11-01

    Full Text Available Abstract Background Telmisartan is a well-established angiotensin II type 1 receptor blocker that improves insulin sensitivity in animal models of obesity and insulin resistance, as well as in humans. Telmisartan has been reported to function as a partial agonist of the peroxisome proliferator-activated receptor (PPAR γ, which is also targeted by the nicotinamide adenine dinucleotide (NAD-dependent deacetylase (SIRT1. Here, we investigated the pathways through which telmisartan acts on skeletal muscle, in vitro as well as in vivo. Methods Nine-week-old male db/db mice were fed a 60% high-fat diet, with orally administrated either vehicle (carboxymethyl-cellulose, CMC, 5 mg/kg telmisartan, or 5 mg/kg telmisartan and 1 mg/kg GW9662, a selective irreversible antagonist of PPARγ, for 5 weeks. Effects of telmisartan on Sirt1 mRNA, AMPK phosphorylation, and NAD+/NADH ratio were determined in C2C12 cultured myocytes. Results and discussion Telmisartan treatment improved insulin sensitivity in obese db/db mice fed a high-fat diet and led to reduction in the size of hypertrophic pancreatic islets in these mice. Moreover, in vitro treatment with telmisartan led to increased expression of Sirt1 mRNA in C2C12 skeletal muscle cells; the increase in Sirt1 mRNA in telmisartan-treated C2C12 myoblasts occurred concomitantly with an increase in AMPK phosphorylation, an increase in NAD+/NADH ratio, and increases in the mRNA levels of PGC1α, FATP1, ACO, and GLUT4. Conclusions Our results indicate that telmisartan acts through a PPARγ-independent pathway, but at least partially exerts its effects by acting directly on skeletal muscle AMPK/SIRT1 pathways.

  20. Elevation of serum insulin concentration during euglycemic hyperinsulinemic clamp studies leads to similar activation of insulin receptor kinase in skeletal muscle of subjects with and without NIDDM

    DEFF Research Database (Denmark)

    Klein, H H; Vestergaard, H; Kotzke, G

    1995-01-01

    The role of skeletal muscle insulin receptor kinase in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) was investigated. Muscle biopsies from 13 patients with NIDDM and 10 control subjects at fasting serum insulin concentrations and approximately 1,000 pmol/l steady-state serum...... insulin during euglycemic hyperinsulinemic clamps were immediately frozen. The biopsies were then solubilized, and the receptors were immobilized to anti-insulin receptor antibody-coated microwells. Receptor kinase and binding activities were consecutively measured in these wells. The increase in serum...... and control groups, respectively). Moreover, by selecting only the receptors that bound to anti-phosphotyrosine antibody, we found similar hyperinsulinemia-induced increases of this receptor fraction and its kinase activity in both study groups. In vitro activation of the immobilized receptors with 2 mmol...

  1. Role of intensive training in the growth and maturation of artistic gymnasts.

    Science.gov (United States)

    Malina, Robert M; Baxter-Jones, Adam D G; Armstrong, Neil; Beunen, Gaston P; Caine, Dennis; Daly, Robin M; Lewis, Richard D; Rogol, Alan D; Russell, Keith

    2013-09-01

    Short stature and later maturation of youth artistic gymnasts are often attributed to the effects of intensive training from a young age. Given limitations of available data, inadequate specification of training, failure to consider other factors affecting growth and maturation, and failure to address epidemiological criteria for causality, it has not been possible thus far to establish cause-effect relationships between training and the growth and maturation of young artistic gymnasts. In response to this ongoing debate, the Scientific Commission of the International Gymnastics Federation (FIG) convened a committee to review the current literature and address four questions: (1) Is there a negative effect of training on attained adult stature? (2) Is there a negative effect of training on growth of body segments? (3) Does training attenuate pubertal growth and maturation, specifically, the rate of growth and/or the timing and tempo of maturation? (4) Does training negatively influence the endocrine system, specifically hormones related to growth and pubertal maturation? The basic information for the review was derived from the active involvement of committee members in research on normal variation and clinical aspects of growth and maturation, and on the growth and maturation of artistic gymnasts and other youth athletes. The committee was thus thoroughly familiar with the literature on growth and maturation in general and of gymnasts and young athletes. Relevant data were more available for females than males. Youth who persisted in the sport were a highly select sample, who tended to be shorter for chronological age but who had appropriate weight-for-height. Data for secondary sex characteristics, skeletal age and age at peak height velocity indicated later maturation, but the maturity status of gymnasts overlapped the normal range of variability observed in the general population. Gymnasts as a group demonstrated a pattern of growth and maturation similar to

  2. STING activation enhances cetuximab-mediated NK cell activation and DC maturation and correlates with HPV+ status in head and neck cancer.

    Science.gov (United States)

    Lu, Shanhong; Concha-Benavente, Fernando; Shayan, Gulidanna; Srivastava, Raghvendra M; Gibson, Sandra P; Wang, Lin; Gooding, William E; Ferris, Robert L

    2018-03-01

    The intracellular DNA sensor stimulator of interferon genes (STING) has recently been shown to play a vital role in anti-viral and anti-tumor immune responses stimulating cytokine production. While human papillomavirus (HPV) is a causative agent for a subset of head and neck squamous cell carcinoma (HNSCC) with unique etiology and clinical outcome, how the STING pathway is regulated in a virus-induced tumor microenvironment is not well understood. Since STING inactivation likely reflects immunoescape via innate immunity, we hypothesized that its restoration would improve efficacy of the immune modulatory monoclonal antibody (mAb), cetuximab. We correlated STING protein expression with clinical parameters by immunohistochemistry (n = 106) and its mRNA expression from The Cancer Genome Atlas (TCGA) in HNSCC tissue specimens. STING protein expression was tested for association with cancer-specific survival (CSS). We further examined the impact of STING activation on cetuximab-mediated immunity using an in vitro NK:DC:tumor cells co-culture system. In this study, we found that expression of STING both at the protein and mRNA level was higher in HPV positive (HPV + ) specimens but unrelated to TNM stage or cancer-specific survival. Our in vitro studies verified that STING activation enhanced cetuximab mediated NK cell activation and DC maturation. Our findings suggest a novel role of STING in HPV-related carcinogenesis, in which activation of the STING signaling pathway may facilitate anti-tumor response in HNSCC patients, particularly in combination with therapeutic monoclonal antibodies (mAbs) such as cetuximab, an epidermal growth factor receptor (EGFR) inhibitor. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Antigen-specific IL-23/17 pathway activation by murine semi-mature DC-like cells

    Energy Technology Data Exchange (ETDEWEB)

    Nagasaka, Shinya; Iwasaki, Takumi; Okano, Tomoko [Department of Biological Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510 (Japan); Chiba, Joe, E-mail: chibaj@rs.noda.tus.ac.jp [Department of Biological Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510 (Japan)

    2009-09-11

    We analyzed the phenotype and function of bone marrow-derived dendritic cells (DCs) induced in vitro without using any serum during the late stage of cultivation. These 'serum-free' DCs (SF-DCs) possessed the ability to induce T cell proliferation as well as antibody responses, indicating that they were functional DCs. Surprisingly, the SF-DCs akin to semi-mature DCs in terms of both phenotypic and functional characteristics. The SF-DCs did not produce IL-12 but produced large amounts of IL-23 following lipopolysaccharide stimulation. The antigen-specific production of IL-17 by CD4{sup +} T cells co-cultured with OVA-loaded SF-DCs was significantly higher than that with OVA-loaded conventional DCs. These results suggest that SF-DCs tend to produce IL-23 and can consequently induce the IL-17 producing CD4{sup +} T cells. The semi-mature DC-like cells reported here will be useful vehicles for DC immunization and might contribute to studies on the possible involvement of semi-mature DCs in Th17 cell differentiation.

  4. Avaliação da reprodutibilidade do método de determinação da maturação esquelética por meio das vértebras cervicais Evaluation of the reproducibility of the method of determination of the skeletal maturation by cervical vertebrae

    Directory of Open Access Journals (Sweden)

    Eduardo César Almada Santos

    2005-04-01

    Full Text Available Dentre os diversos meios de se determinar o grau de maturação esquelética do paciente destaca-se o Método de Lamparski modificado por Hassel e Farman, em 1995, que propuseram a identificação do estágio da maturação por meio das modificações anatômicas das 2ª, 3ª e 4ª vértebras cervicais. Cientes das qualidades advogadas ao método citado surgiu o interesse em avaliar sua reprodutibilidade com o intuito de divulgá-lo e incorporá-lo como um elemento no diagnóstico e auxiliar no prognóstico dos tratamentos das más oclusões. A amostra constou de 100 telerradiografias em norma lateral de pacientes triados para tratamento ortodôntico na Faculdade de Odontologia de Araçatuba - UNESP nos períodos de 2000 e 2001. Foram incluídos pacientes de ambos os gêneros na faixa etária de 6 a 16 anos e a média de 9 anos e 7 meses. Três examinadores devidamente calibrados realizaram a avaliação das radiografias classificando-as em escores de 1 a 6. Após a análise dos resultados, os mesmos foram tabulados e submetidos ao coeficiente Kappa de concordância para avaliação inter e intra-examinador concluindo, dessa forma, a reprodutibilidade do referido método. O método de determinação da maturação esquelética por meio das vértebras cervicais mostrou-se reproduzível na avaliação do estágio em que o indivíduo se encontra na curva de crescimento.Among the different ways to determine the degree of the skeletal maturation of the patient, the Lamparski method stands out modified by Hassel e Farman that proposed the identification of the maturation stage throught anatomic changes of the 2nd, 3rd and 4rth cervical vertebrae. Awere of the qualities conferred to the quoted method emerged the interest about evaluating its reprodutictibility with the aim of divulge and incorporate it as an element in diagnoses and as an auxiliary in the prognoses of the malocclusion treatment. The sample presented 100 teleradiographs in lateral norm

  5. Application of skeletal age based on x-ray in selecting sports talents

    Science.gov (United States)

    Mao, Zongzhen; Xu, Guodong; Song, Tao

    2012-01-01

    Skeletal age has been studied and proved that for most elite athletes, it was coincident with the chronological ages when they were young. In order to explore the application of skeletal age in selecting sports talent, 32 athletes (female, chronological age 5-12 y) were chosen from the Gymnastics Training Base in this study. Their left hand-wrists were photographed with X-rays, and then the skeletal ages were estimated by Chinese version of the Tanner-Whitehouse Skeletal Maturity Assessment System. At the same time, their body shapes, functions, and sports ability were also measured. Results showed that 71.88% of the skeletal age was proportional to their chronological age (+/- 1 y); while 18.75% of the skeletal maturity was retarded by 1- 2 year, 9.37% of those was advanced more than 1 year. On the other hand, the body shape, functions and sports ability of the athletes were positively related with their skeletal maturity. This study proved that the determination of skeletal maturity is a reliable evaluation for selecting sports talent. A further study on the influence of gymnastics on the skeletal age is of great significance.

  6. High Fat Diet-Induced Skeletal Muscle Wasting Is Decreased by Mesenchymal Stem Cells Administration: Implications on Oxidative Stress, Ubiquitin Proteasome Pathway Activation, and Myonuclear Apoptosis

    Directory of Open Access Journals (Sweden)

    Johanna Abrigo

    2016-01-01

    Full Text Available Obesity can lead to skeletal muscle atrophy, a pathological condition characterized by the loss of strength and muscle mass. A feature of muscle atrophy is a decrease of myofibrillar proteins as a result of ubiquitin proteasome pathway overactivation, as evidenced by increased expression of the muscle-specific ubiquitin ligases atrogin-1 and MuRF-1. Additionally, other mechanisms are related to muscle wasting, including oxidative stress, myonuclear apoptosis, and autophagy. Stem cells are an emerging therapy in the treatment of chronic diseases such as high fat diet-induced obesity. Mesenchymal stem cells (MSCs are a population of self-renewable and undifferentiated cells present in the bone marrow and other mesenchymal tissues of adult individuals. The present study is the first to analyze the effects of systemic MSC administration on high fat diet-induced skeletal muscle atrophy in the tibialis anterior of mice. Treatment with MSCs reduced losses of muscle strength and mass, decreases of fiber diameter and myosin heavy chain protein levels, and fiber type transitions. Underlying these antiatrophic effects, MSC administration also decreased ubiquitin proteasome pathway activation, oxidative stress, and myonuclear apoptosis. These results are the first to indicate that systemically administered MSCs could prevent muscle wasting associated with high fat diet-induced obesity and diabetes.

  7. [3H]PN200-110 and [3H]ryanodine binding and reconstitution of ion channel activity with skeletal muscle membranes

    International Nuclear Information System (INIS)

    Hamilton, S.L.; Alvarez, R.M.; Fill, M.; Hawkes, M.J.; Brush, K.L.; Schilling, W.P.; Stefani, E.

    1989-01-01

    Skeletal muscle membranes derived either from the tubular (T) network or from the sarcoplasmic reticulum (SR) were characterized with respect to the binding of the dihydropyridine, [ 3 H]PN200-110, and the alkaloid, [ 3 H]ryanodine; polypeptide composition; and ion channel activity. Conditions for optimizing the binding of these radioligands are discussed. A bilayer pulsing technique is described and is used to examine the channels present in these membranes. Fusion of T-tubule membranes into bilayers revealed the presence of chloride channels and dihydropyridine-sensitive calcium channels with three distinct conductances. The dihydropyridine-sensitive channels were further characterized with respect to their voltage dependence. Pulsing experiments indicated that two different populations of dihydropyridine-sensitive channels existed. Fusion of heavy SR vesicles revealed three different ion channels; the putative calcium release channel, a potassium channel, and a chloride channel. Thus, this fractionation procedure provides T-tubules and SR membranes which, with radioligand binding and single channel recording techniques, provide a useful tool to study the characteristics of skeletal muscle ion channels and their possible role in excitation-contraction coupling

  8. Is Greulich–Pyle age estimation applicable for determining maturation in male Africans?

    Directory of Open Access Journals (Sweden)

    Alan G. Morri

    2012-09-01

    Full Text Available Skeletal age estimation as a means of assessing development and skeletal maturation in children and adolescents is of great importance for clinical and forensic purposes. The skeletal age of a test population is estimated by comparison with established standards, the most common standards being those in the Radiographic atlas of skeletal development of the hand and wristpublished by Greulich and Pyle in 1959. These standards are based on the assumption that skeletal maturity in male individuals is attained by the chronological age of 19 years. Although they have been widely tested, the applicability of these standards to contemporary populations has yet to be tested on a population of African biological origin living in South Africa. We therefore estimated the skeletal age of 131 male Africans aged between 13 and 21 years, using the Greulich–Pyle method which we applied to pre-existing hand–wrist radiographs. Estimated skeletal age was compared to the known chronological age for each radiograph. Skeletal age was on average approximately 6 months younger than chronological age. The Greulich–Pyle method underestimated skeletal age for approximately 74%of the sample and overestimated skeletal age for 26%of the sample. Skeletal maturity as characterised by complete epiphyseal fusion occurred approximately 2.1 years later than Greulich and Pyle’s estimate of 19 years. Thus skeletal maturation was still in progress in a large proportion of the 20- and 21-year-old individuals in our study. The Greulich–Pyle method showed high precision but low accuracy and was therefore not directly applicable to African male individuals. Formulation of skeletal age estimation standards specific to South African populations is therefore recommended.

  9. Exogenous Thyropin from p41 Invariant Chain Diminishes Cysteine Protease Activity and Affects IL-12 Secretion during Maturation of Human Dendritic Cells.

    Directory of Open Access Journals (Sweden)

    Tina Zavašnik-Bergant

    Full Text Available Dendritic cells (DC play a pivotal role as antigen presenting cells (APC and their maturation is crucial for effectively eliciting an antigen-specific immune response. The p41 splice variant of MHC class II-associated chaperone, called invariant chain p41 Ii, contains an amino acid sequence, the p41 fragment, which is a thyropin-type inhibitor of proteolytic enzymes. The effects of exogenous p41 fragment and related thyropin inhibitors acting on human immune cells have not been reported yet. In this study we demonstrate that exogenous p41 fragment can enter the endocytic pathway of targeted human immature DC. Internalized p41 fragment has contributed to the total amount of the immunogold labelled p41 Ii-specific epitope, as quantified by transmission electron microscopy, in particular in late endocytic compartments with multivesicular morphology where antigen processing and binding to MHC II take place. In cell lysates of treated immature DC, diminished enzymatic activity of cysteine proteases has been confirmed. Internalized exogenous p41 fragment did not affect the perinuclear clustering of acidic cathepsin S-positive vesicles typical of mature DC. p41 fragment is shown to interfere with the nuclear translocation of NF-κB p65 subunit in LPS-stimulated DC. p41 fragment is also shown to reduce the secretion of interleukin-12 (IL-12/p70 during the subsequent maturation of treated DC. The inhibition of proteolytic activity of lysosomal cysteine proteases in immature DC and the diminished capability of DC to produce IL-12 upon their subsequent maturation support the immunomodulatory potential of the examined thyropin from p41 Ii.

  10. Studies of gene expression and activity of hexokinase, phosphofructokinase and glycogen synthase in human skeletal muscle in states of altered insulin-stimulated glucose metabolism

    DEFF Research Database (Denmark)

    Vestergaard, H

    1999-01-01

    been reported to increase the basal concentration of muscle GS mRNA in NIDDM patients to a level similar to that seen in control subjects although insulin-stimulated glucose disposal rates remain reduced in NIDDM patients. In the insulin resistant states examined so far, basal and insulin-stimulated......When whole body insulin-stimulated glucose disposal rate is measured in man applying the euglycaemic, hyperinsulinaemic clamp technique it has been shown that approximately 75% of glucose is taken up by skeletal muscle. After the initial transport step, glucose is rapidly phosphorylated to glucose...... critical roles in glucose oxidation/glycolysis and glucose storage, respectively. Glucose transporters and glycogen synthase activities are directly and acutely stimulated by insulin whereas the activities of hexokinases and phosphofructokinase may primarily be allosterically regulated. The aim...

  11. Type 2 diabetes is associated with altered NF-¿B DNA binding activity, JNK phosphorylation, and AMPK phosphorylation in skeletal muscle after LPS

    DEFF Research Database (Denmark)

    Andreasen, Anne Sofie; Kelly, Meghan; Berg, Ronan Martin Griffin

    2011-01-01

    Systemic inflammation is often associated with impaired glucose metabolism. We therefore studied the activation of inflammatory pathway intermediates that interfere with glucose uptake during systemic inflammation by applying a standardised inflammatory stimulus in vivo. After ethical approval......, informed consent and a thorough physical examination, 10 patients with type 2 diabetes and 10 participants with normal glucose tolerance (NGT) were given an intravenous bolus of E. coli lipopolysaccharide (LPS) of 0.3 ng/kg. Skeletal muscle biopsies and plasma were obtained at baseline and two, four...... and six hours after LPS. Nuclear factor (NF)-¿B p65 DNA binding activity measured by ELISA, tumor necrosis factor-a and interleukin-6 mRNA expression analysed by real time reverse transcription polymerase chain reaction, and abundance of inhibitor of NF-¿B (I¿B)a, phosphorylated c-Jun-N-terminal kinase...

  12. Caffeine and contraction synergistically stimulate 5′-AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscle

    Science.gov (United States)

    Tsuda, Satoshi; Egawa, Tatsuro; Kitani, Kazuto; Oshima, Rieko; Ma, Xiao; Hayashi, Tatsuya

    2015-01-01

    5′-Adenosine monophosphate-activated protein kinase (AMPK) has been identified as a key mediator of contraction-stimulated insulin-independent glucose transport in skeletal muscle. Caffeine acutely stimulates AMPK in resting skeletal muscle, but it is unknown whether caffeine affects AMPK in contracting muscle. Isolated rat epitrochlearis muscle was preincubated and then incubated in the absence or presence of 3 mmol/L caffeine for 30 or 120 min. Electrical stimulation (ES) was used to evoke tetanic contractions during the last 10 min of the incubation period. The combination of caffeine plus contraction had additive effects on AMPKα Thr172 phosphorylation, α-isoform-specific AMPK activity, and 3-O-methylglucose (3MG) transport. In contrast, caffeine inhibited basal and contraction-stimulated Akt Ser473 phosphorylation. Caffeine significantly delayed muscle fatigue during contraction, and the combination of caffeine and contraction additively decreased ATP and phosphocreatine contents. Caffeine did not affect resting tension. Next, rats were given an intraperitoneal injection of caffeine (60 mg/kg body weight) or saline, and the extensor digitorum longus muscle was dissected 15 min later. ES of the sciatic nerve was performed to evoke tetanic contractions for 5 min before dissection. Similar to the findings from isolated muscles incubated in vitro, the combination of caffeine plus contraction in vivo had additive effects on AMPK phosphorylation, AMPK activity, and 3MG transport. Caffeine also inhibited basal and contraction-stimulated Akt phosphorylation in vivo. These findings suggest that caffeine and contraction synergistically stimulate AMPK activity and insulin-independent glucose transport, at least in part by decreasing muscle fatigue and thereby promoting energy consumption during contraction. PMID:26471759

  13. Caffeine and contraction synergistically stimulate 5'-AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscle.

    Science.gov (United States)

    Tsuda, Satoshi; Egawa, Tatsuro; Kitani, Kazuto; Oshima, Rieko; Ma, Xiao; Hayashi, Tatsuya

    2015-10-01

    5'-Adenosine monophosphate-activated protein kinase (AMPK) has been identified as a key mediator of contraction-stimulated insulin-independent glucose transport in skeletal muscle. Caffeine acutely stimulates AMPK in resting skeletal muscle, but it is unknown whether caffeine affects AMPK in contracting muscle. Isolated rat epitrochlearis muscle was preincubated and then incubated in the absence or presence of 3 mmol/L caffeine for 30 or 120 min. Electrical stimulation (ES) was used to evoke tetanic contractions during the last 10 min of the incubation period. The combination of caffeine plus contraction had additive effects on AMPKα Thr(172) phosphorylation, α-isoform-specific AMPK activity, and 3-O-methylglucose (3MG) transport. In contrast, caffeine inhibited basal and contraction-stimulated Akt Ser(473) phosphorylation. Caffeine significantly delayed muscle fatigue during contraction, and the combination of caffeine and contraction additively decreased ATP and phosphocreatine contents. Caffeine did not affect resting tension. Next, rats were given an intraperitoneal injection of caffeine (60 mg/kg body weight) or saline, and the extensor digitorum longus muscle was dissected 15 min later. ES of the sciatic nerve was performed to evoke tetanic contractions for 5 min before dissection. Similar to the findings from isolated muscles incubated in vitro, the combination of caffeine plus contraction in vivo had additive effects on AMPK phosphorylation, AMPK activity, and 3MG transport. Caffeine also inhibited basal and contraction-stimulated Akt phosphorylation in vivo. These findings suggest that caffeine and contraction synergistically stimulate AMPK activity and insulin-independent glucose transport, at least in part by decreasing muscle fatigue and thereby promoting energy consumption during contraction. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological

  14. Skeletal muscle gene expression after myostatin knockout in mature mice Address for reprint requests and other correspondence: S. Welle, Univ. of Rochester Medical Center, 601 Elmwood Ave., Box 693, Rochester, NY 14642 (e-mail: ).

    OpenAIRE

    Welle, Stephen; Cardillo, Andrew; Zanche, Michelle; Tawil, Rabi

    2009-01-01

    There is much interest in developing anti-myostatin agents to reverse or prevent muscle atrophy in adults, so it is important to characterize the effects of reducing myostatin activity after normal muscle development. For assessment of the effect of loss of myostatin signaling on gene expression in muscle, RNA from mice with postdevelopmental myostatin knockout was analyzed with oligonucleotide microarrays. Myostatin was undetectable in muscle within 2 wk after Cre recombinase activation in 4...

  15. Induced skeletal mutations

    International Nuclear Information System (INIS)

    Selby, P.B.

    1979-01-01

    This paper describes a large-scale experiment that, by means of breeding tests, confirmed that many dominant skeletal mutations are induced by large-dose radiation exposure. The author also discusses: (1) the major advantages and disadvantages of the skeletal method in improving estimates of genetic hazard to man; (2) future uses of the skeletal method; (3) direct estimation of risk beyond the first generation using the skeletal method; and (4) the possibility of using the skeletal method as a quick and easy screen for chemical mutagens

  16. Correlation between Cervical Vertebral Maturation Stages and Dental Maturation in a Saudi Sample

    Directory of Open Access Journals (Sweden)

    Nayef H Felemban

    2017-01-01

    Full Text Available Background: The aim of the present study was to compare the cervical vertebra maturation stages method and dental maturity using tooth calcification stages. Methods: The current study comprised of 405 subjects selected from orthodontic patients of Saudi origin coming to clinics of the specialized dental centers in western region of Saudi Arabia. Dental age was assessed according to the developmental stages of upper and lower third molars and skeletal maturation according to the cervical vertebrae maturation stage method. Statistical analysis was done using Kruskal-Wallis H, Mann-Whitney U test, Chi-Square test; t-test and Spearman correlation coefficient for inter group comparison. Results: The females were younger than males in all cervical stages. The CS1-CS2 show the period before the peak of growth, during CS3-CS5 it’s the pubertal growth spurt and CS6 is the period after the peak of the growth. The mean age and standard deviation for cervical stages of CS2, CS3 and CS4 were 12.09 ±1.72 years, 13.19 ±1.62 and 14.88 ±1.52 respectively. The Spearman correlation coefficients between cervical vertebrae and dental maturation were between 0.166 and 0.612, 0.243 and 0.832 for both sexes for upper and lower third molars. The significance levels for all coefficients were equal at 0.01 and 0.05. Conclusion: The results of this study showed that the skeletal maturity increased with the increase in dental ages for both genders. An early rate of skeletal maturation stage was observed in females. This study needs further analysis using a larger sample covering the entire dentition.

  17. Quantitative skeletal scintiscanning

    International Nuclear Information System (INIS)

    Haushofer, R.

    1982-01-01

    330 patients were examined by skeletal scintiscanning with sup(99m)Tc pyrophosphate and sup(99m)methylene diphosphonate in the years between 1977 and 1979. Course control examinations were carried out in 12 patients. The collective of patients presented with primary skeletal tumours, metastases, inflammatory and degenerative skeletal diseases. Bone scintiscanning combined with the ''region of interest'' technique was found to be an objective and reproducible technique for quantitative measurement of skeletal radioactivity concentrations. The validity of nuclear skeletal examinations can thus be enhanced as far as diagnosis, course control, and differential diagnosis are concerned. Quantitative skeletal scintiscanning by means of the ''region of interest'' technique has opened up a new era in skeletal diagnosis by nuclear methods. (orig./MG) [de

  18. Protein kinase N2 regulates AMP kinase signaling and insulin responsiveness of glucose metabolism in skeletal muscle.

    Science.gov (United States)

    Ruby, Maxwell A; Riedl, Isabelle; Massart, Julie; Åhlin, Marcus; Zierath, Juleen R

    2017-10-01

    Insulin resistance is central to the development of type 2 diabetes and related metabolic disorders. Because skeletal muscle is responsible for the majority of whole body insulin-stimulated glucose uptake, regulation of glucose metabolism in this tissue is of particular importance. Although Rho GTPases and many of their affecters influence skeletal muscle metabolism, there is a paucity of information on the protein kinase N (PKN) family of serine/threonine protein kinases. We investigated the impact of PKN2 on insulin signaling and glucose metabolism in primary human skeletal muscle cells in vitro and mouse tibialis anterior muscle in vivo. PKN2 knockdown in vitro decreased insulin-stimulated glucose uptake, incorporation into glycogen, and oxidation. PKN2 siRNA increased 5'-adenosine monophosphate-activated protein kinase (AMPK) signaling while stimulating fatty acid oxidation and incorporation into triglycerides and decreasing protein synthesis. At the transcriptional level, PKN2 knockdown increased expression of PGC-1α and SREBP-1c and their target genes. In mature skeletal muscle, in vivo PKN2 knockdown decreased glucose uptake and increased AMPK phosphorylation. Thus, PKN2 alters key signaling pathways and transcriptional networks to regulate glucose and lipid metabolism. Identification of PKN2 as a novel regulator of insulin and AMPK signaling may provide an avenue for manipulation of skeletal muscle metabolism. Copyright © 2017 the American Physiological Society.

  19. Activation by insulin and amino acids of signaling components leading to translation initiation in skeletal muscle of neonatal pigs is developmentally regulated.

    Science.gov (United States)

    Suryawan, Agus; Orellana, Renan A; Nguyen, Hanh V; Jeyapalan, Asumthia S; Fleming, Jillian R; Davis, Teresa A

    2007-12-01

    Insulin and amino acids act independently to stimulate protein synthesis in skeletal muscle of neonatal pigs, and the responses decrease with development. The purpose of this study was to compare the separate effects of fed levels of INS and AA on the activation of signaling components leading to translation initiation and how these responses change with development. Overnight-fasted 6- (n = 4/group) and 26-day-old (n = 6/ group) pigs were studied during 1) euinsulinemic-euglycemiceuaminoacidemic conditions (controls), 2) euinsulinemic-euglycemichyperaminoacidemic clamps (AA), and 3) hyperinsulinemic-euglycemic-euaminoacidemic clamps (INS). INS, but not AA, increased the phosphorylation of protein kinase B (PKB) and tuberous sclerosis 2 (TSC2). Both INS and AA increased protein synthesis and the phosphorylation of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase-1, and eukaryotic initiation factor (eIF)4E-binding protein 1 (4E-BP1), and these responses were higher in 6-day-old compared with 26-day-old pigs. Both INS and AA decreased the binding of 4E-BP1 to eIF4E and increased eIF4E binding to eIF4G; these effects were greater in 6-day-old than in 26-day-old pigs. Neither INS nor AA altered the composition of mTORC1 (raptor, mTOR, and GbetaL) or mTORC2 (rictor, mTOR, and GbetaL) complexes. Furthermore, neither INS, AA, nor age had any effect on the abundance of Rheb and the phosphorylation of AMP-activated protein kinase and eukaryotic elongation factor 2. Our results suggest that the activation by insulin and amino acids of signaling components leading to translation initiation is developmentally regulated and parallels the developmental decline in protein synthesis in skeletal muscle of neonatal pigs.

  20. Peroxisomes in Different Skeletal Cell Types during Intramembranous and Endochondral Ossification and Their Regulation during Osteoblast Differentiation by Distinct Peroxisome Proliferator-Activated Receptors.

    Directory of Open Access Journals (Sweden)

    Guofeng Qian

    Full Text Available Ossification defects leading to craniofacial dysmorphism or rhizomelia are typical phenotypes in patients and corresponding knockout mouse models with distinct peroxisomal disorders. Despite these obvious skeletal pathologies, to date no careful analysis exists on the distribution and function of peroxisomes in skeletal tissues and their alterations during ossification. Therefore, we analyzed the peroxisomal compartment in different cell types of mouse cartilage and bone as well as in primary cultures of calvarial osteoblasts. The peroxisome number and metabolism strongly increased in chondrocytes during endochondral ossification from the reserve to the hypertrophic zone, whereas in bone, metabolically active osteoblasts contained a higher numerical abundance of this organelle than osteocytes. The high abundance of peroxisomes in these skeletal cell types is reflected by high levels of Pex11β gene expression. During culture, calvarial pre-osteoblasts differentiated into secretory osteoblasts accompanied by peroxisome proliferation and increased levels of peroxisomal genes and proteins. Since many peroxisomal genes contain a PPAR-responsive element, we analyzed the gene expression of PPARɑ/ß/ɣ in calvarial osteoblasts and MC3T3-E1 cells, revealing higher levels for PPARß than for PPARɑ and PPARɣ. Treatment with different PPAR agonists and antagonists not only changed the peroxisomal compartment and associated gene expression, but also induced complex alterations of the gene expression patterns of the other PPAR family members. Studies in M3CT3-E1 cells showed that the PPARß agonist GW0742 activated the PPRE-mediated luciferase expression and up-regulated peroxisomal gene transcription (Pex11, Pex13, Pex14, Acox1 and Cat, whereas the PPARß antagonist GSK0660 led to repression of the PPRE and a decrease of the corresponding mRNA levels. In the same way, treatment of calvarial osteoblasts with GW0742 increased in peroxisome number and

  1. Reduced plasma adiponectin concentrations may contribute to impaired insulin activation of glycogen synthase in skeletal muscle of patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Højlund, K.; Frystyk, J.; Levin, K.

    2006-01-01

    AIMS/HYPOTHESIS: Circulating levels of adiponectin are negatively associated with multiple indices of insulin resistance, and the concentration is reduced in humans with insulin resistance and type 2 diabetes. However, the mechanisms by which adiponectin improves insulin sensitivity remain unclear...... (ten lean, 21 obese and 20 with type 2 diabetes). RESULTS: Plasma adiponectin was significantly reduced in type 2 diabetic compared with obese and lean subjects. In lean and obese subjects, insulin significantly reduced plasma adiponectin, but this response was blunted in patients with type 2 diabetes...... by improving the capacity to switch from lipid to glucose oxidation and to store glucose as glycogen in response to insulin, and that low adiponectin may contribute to impaired insulin activation of GS in skeletal muscle of patients with type 2 diabetes....

  2. Toxicity effect of Auxemma oncocalyx fraction and its active principle oncocalyxone A on in vitro culture of caprine secondary follicles and in vitro oocyte maturation

    Directory of Open Access Journals (Sweden)

    Johanna Leiva-Revilla

    2017-06-01

    Full Text Available Crude extract of the heartwood of Auxemma oncocalyx (A. oncocalyx and its main component i.e., Oncocalyxone A (onco A, have elevated antioxidant and anti-tumoral activity, but studies on the action of these drugs regarding folliculogenesis are lacking. The aim of this study was to evaluate the effect of A. oncocalyx and onco A on the in vitro culture of isolated secondary follicles and on the in vitro maturation of oocytes from caprine antral follicles grown in vivo. Isolated secondary follicles were randomly distributed in six groups; the non-cultured control was immediately fixed upon isolation. The remaining follicles were cultured for 7 days in ?-MEM+ alone (control or supplemented with DMSO, doxorrubicin, A. oncocalyx or onco A. After culture, follicles were evaluated for antrum formation, growth rate, apoptosis (TUNEL and cellular proliferation (PCNA, as well as gene expression of Bcl2 and Bax. Additionally, cumulus oocyte complexes (COCs were aspirated and allocated into five treatments for in vitro maturation: control, cultured only in maturation base medium (TCM 199+; or supplemented with DMSO; DXR; A. oncocalyx or onco A. After in vitro maturation, oocyte chromatin configuration and viability were assessed. After 7 days of culture, there was a reduction (P < 0.05 in the percentage of morphologically intact follicles, antrum formation, growth rate and number of PCNA positive granulosa cells in DXR treatment compared to the other treatments. In the DXR treatment a higher percentage (P < 0.05 of TUNEL positive follicles and higher (P < 0.05 relative BAX:BCL2 mRNA ratio’s were observed. After in vitro maturation of the COCs DXR, A. oncocalyx and onco A treatments had a greater (P < 0.05 percentage of abnormal oocytes and a lower (P < 0.05 percentage of viable oocytes as compared with the control group. However, only DXR and onco A treatments increased (P < 0.05 the percentage of alive oocytes with

  3. Nitric oxide increases cyclic GMP levels, AMP-activated protein kinase (AMPK)alpha1-specific activity and glucose transport in human skeletal muscle

    DEFF Research Database (Denmark)

    Deshmukh, A S; Long, Y C; de Castro Barbosa, T

    2010-01-01

    -nitrosohydrazino)-1,2-ethylenediamine (spermine NONOate) would increase intracellular cyclic GMP (cGMP) levels and promote glucose transport. METHODS: Skeletal muscle strips were prepared from vastus lateralis muscle biopsies obtained from seven healthy men. Muscle strips were incubated in the absence or presence...... of 5 mmol/l spermine NONOate or 120 nmol/l insulin. The L6 muscle cells were treated with spermine NONOate (20 micromol/l) and incubated in the absence or presence of insulin (120 nmol/l). The direct effect of spermine NONOate and insulin on glucose transport, cGMP levels and signal transduction...... was determined. RESULTS: In human skeletal muscle, spermine NONOate increased glucose transport 2.4-fold (p GMP levels (80-fold, p

  4. An Anti-Urokinase Plasminogen Activator Receptor Antibody (ATN-658 Blocks Prostate Cancer Invasion, Migration, Growth, and Experimental Skeletal Metastasis In Vitro and In Vivo

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    Shafaat A. Rabbani

    2010-10-01

    Full Text Available Urokinase plasminogen activator receptor (uPAR is a multidomain protein that plays important roles in the growth, invasion, and metastasis of a number of cancers. In the present study, we examined the effects of administration of a monoclonal anti-uPAR antibody (ATN-658 on prostate cancer progression in vitro and in vivo. We examined the effect of treatment of ATN-658 on human prostate cancer cell invasion, migration, proliferation, and regulation of intracellular signaling pathways. For in vivo studies, PC-3 cells (1 x 106 were inoculated into the right flank of male Balb C nu/nu mice through subcutaneous or through intratibial route (2 x 105 of male Fox Chase severe combined immunodeficient mice to monitor the effect on tumor growth and skeletal metastasis. Treatment with ATN-658 resulted in a significant dose-dependent decrease in PC-3 cell invasion and migration without affecting cell doubling time. Western blot analysis showed that ATN-658 treatment decreased the phosphorylation of serine/threonine protein kinase B (AKT, mitogen-activated protein kinase (MAPK, and focal adhesion kinase (FAK without affecting AKT, MAPK, and FAK total protein expression. In in vivo studies, ATN-658 caused a significant decrease in tumor volume and a marked reduction in skeletal lesions as determined by Faxitron x-ray and micro-computed tomography. Immunohistochemical analysis of subcutaneous and tibial tumors showed a marked decrease in the levels of expression of pAKT, pMAPK, and pFAK, consistent with the in vitro observations. Results from these studies provide compelling evidence for the continued development of ATN-658 as a potential therapeutic agent for the treatment of prostate and other cancers expressing uPAR.

  5. Cardiac, Skeletal, and smooth muscle mitochondrial respiration

    DEFF Research Database (Denmark)

    Park, Song-Young; Gifford, Jayson R; Andtbacka, Robert H I

    2014-01-01

    , skeletal, and smooth muscle was harvested from a total of 22 subjects (53±6 yrs) and mitochondrial respiration assessed in permeabilized fibers. Complex I+II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac, skeletal, to smooth muscle (54±1; 39±4; 15......±1 pmol•s(-1)•mg (-1), prespiration rates were normalized by CS (respiration...... per mitochondrial content), oxidative phosphorylation capacity was no longer different between the three muscle types. Interestingly, Complex I state 2 normalized for CS activity, an index of non-phosphorylating respiration per mitochondrial content, increased progressively from cardiac, skeletal...

  6. MSX2 stimulates chondrocyte maturation by controlling Ihh expression.

    Science.gov (United States)

    Amano, Katsuhiko; Ichida, Fumitaka; Sugita, Atsushi; Hata, Kenji; Wada, Masahiro; Takigawa, Yoko; Nakanishi, Masako; Kogo, Mikihiko; Nishimura, Riko; Yoneda, Toshiyuki

    2008-10-24

    Several studies indicated that a homeobox gene, Msx2, is implicated in regulation of skeletal development by controlling enchondral ossification as well as membranous ossification. However, the molecular basis by which Msx2 conducts chondrogenesis is currently unclear. In this study, we examined the role of Msx2 in chondrocyte differentiation using mouse primary chondrocytes and embryonic metatarsal explants. Treatment with BMP2 up-regulated the expression of Msx2 mRNA along with chondrocyte differentiation in murine primary chondrocytes. Overexpression of wild-type Msx2 stimulated calcification of primary chondrocytes in the presence of BMP2. We also found that constitutively active Msx2 (caMsx2) enhanced BMP2-dependent calcification more efficiently than wild-type Msx2. Consistently, caMsx2 overexpression up-regulated the expression of alkaline phosphatase and collagen type X induced by BMP2. Furthermore, organ culture experiments using mouse embryonic metatarsals indicated that caMsx2 clearly stimulated the maturation of chondrocytes into the prehypertrophic and hypertrophic stages in the presence of BMP2. In contrast, knockdown of Msx2 inhibited maturation of primary chondrocytes. The stimulatory effect of Msx2 on chondrocyte maturation was enhanced by overexpression of Smad1 and Smad4 but inhibited by Smad6, an inhibitory Smad for BMP2 signaling. These data suggest that Msx2 requires BMP2/Smad signaling for its chondrogenic action. In addition, caMsx2 overexpression induced Ihh (Indian hedgehog) expression in mouse primary chondrocytes. Importantly, treatment with cyclopamine, a specific inhibitor for hedgehogs, blocked Msx2-induced chondrogenesis. Collectively, our results indicated that Msx2 promotes the maturation of chondrocytes, at least in part, through up-regulating Ihh expression.

  7. Effect of PDE5 inhibition on the modulation of sympathetic α-adrenergic vasoconstriction in contracting skeletal muscle of young and older recreationally active humans

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Piil, Peter Bergmann; Egelund, Jon

    2015-01-01

    Aging is associated with an altered regulation of blood flow to contracting skeletal muscle; however, the precise mechanisms remain unclear. We recently demonstrated that inhibition of cGMP-binding phosphodiesterase 5 (PDE5) increased blood flow to contracting skeletal muscle of older but not you...

  8. Lyophilized skeletal imaging composition

    International Nuclear Information System (INIS)

    Vanduzee, B.F.

    1983-01-01

    This invention encompasses a process for producing a dry-powder skeletal imaging kit. An aqueous solution of a diphosphonate, a stannous reductant, and, optionally, a stabilizer is prepared. The solution is adjusted to a pH within the range 4.2 to 4.8 and the pH-adjusted solution is then lyophilized. The adjustment of pH, within a particular range, during the process of manufacturing lyophilized diphosphonate containing skeletal imaging kits yields a kit which produces a technetium skeletal imaging agent with superior imaging properties. This improved performance is manifested through faster blood clearance and higher skeletal uptake of the technetium imaging agent

  9. Activation of AMPKα2 is not crucial for mitochondrial uncoupling-induced metabolic effects but required to maintain skeletal muscle integrity.

    Directory of Open Access Journals (Sweden)

    Mario Ost

    Full Text Available Transgenic (UCP1-TG mice with ectopic expression of UCP1 in skeletal muscle (SM show a phenotype of increased energy expenditure, improved glucose tolerance and increase substrate metabolism in SM. To investigate the potential role of skeletal muscle AMPKα2 activation in the metabolic phenotype of UCP1-TG mice we generated double transgenic (DTG mice, by crossing of UCP1-TG mice with DN-AMPKα2 mice overexpressing a dominant negative α2 subunit of AMPK in SM which resulted in an impaired AMPKα2 activity by 90±9% in SM of DTG mice. Biometric analysis of young male mice showed decreased body weight, lean and fat mass for both UCP1-TG and DTG compared to WT and DN-AMPKα2 mice. Energy intake and weight-specific total energy expenditure were increased, both in UCP1-TG and DTG mice. Moreover, glucose tolerance, insulin sensitivity and fatty acid oxidation were not altered in DTG compared to UCP1-TG. Also uncoupling induced induction and secretion of fibroblast growth factor 21 (FGF21 from SM was preserved in DTG mice. However, voluntary physical cage activity as well as ad libitum running wheel access during night uncovered a severe activity intolerance of DTG mice. Histological analysis showed a progressive degenerative morphology in SM of DTG mice which was not observed in SM of UCP1-TG mice. Moreover, ATP-depletion related cellular stress response via heat shock protein 70 was highly induced, whereas capillarization regulator VEGF was suppressed in DTG muscle. In addition, AMPKα2-mediated induction of mitophagy regulator ULK1 was suppressed in DTG mice, as well as mitochondrial respiratory capacity and content. In conclusion, we demonstrate that AMPKα2 is dispensable for SM mitochondrial uncoupling induced metabolic effects on whole body energy balance, glucose homeostasis and insulin sensitivity. But strikingly, activation of AMPKα2 seems crucial for maintaining SM function, integrity and the ability to compensate chronic metabolic stress

  10. Nanosecond electric pulses modulate skeletal muscle calcium dynamics and contraction

    Science.gov (United States)

    Valdez, Chris; Jirjis, Michael B.; Roth, Caleb C.; Barnes, Ronald A.; Ibey, Bennett L.

    2017-02-01

    Irreversible electroporation therapy is utilized to remove cancerous tissues thru the delivery of rapid (250Hz) and high voltage (V) (1,500V/cm) electric pulses across microsecond durations. Clinical research demonstrated that bipolar (BP) high voltage microsecond pulses opposed to monophasic waveforms relieve muscle contraction during electroporation treatment. Our group along with others discovered that nanosecond electric pulses (nsEP) can activate second messenger cascades, induce cytoskeletal rearrangement, and depending on the nsEP duration and frequency, initiate apoptotic pathways. Of high interest across in vivo and in vitro applications, is how nsEP affects muscle physiology, and if nuances exist in comparison to longer duration electroporation applications. To this end, we exposed mature skeletal muscle cells to monopolar (MP) and BP nsEP stimulation across a wide range of electric field amplitudes (1-20 kV/cm). From live confocal microscopy, we simultaneously monitored intracellular calcium dynamics along with nsEP-induced muscle movement on a single cell level. In addition, we also evaluated membrane permeability with Yo-PRO-1 and Propidium Iodide (PI) across various nsEP parameters. The results from our findings suggest that skeletal muscle calcium dynamics, and nsEP-induced contraction exhibit exclusive responses to both MP and BP nsEP exposure. Overall the results suggest in vivo nsEP application may elicit unique physiology and field applications compared to longer pulse duration electroporation.

  11. A Noninvasive In Vitro Monitoring System Reporting Skeletal Muscle Differentiation.

    Science.gov (United States)

    Öztürk-Kaloglu, Deniz; Hercher, David; Heher, Philipp; Posa-Markaryan, Katja; Sperger, Simon; Zimmermann, Alice; Wolbank, Susanne; Redl, Heinz; Hacobian, Ara

    2017-01-01

    Monitoring of cell differentiation is a crucial aspect of cell-based therapeutic strategies depending on tissue maturation. In this study, we have developed a noninvasive reporter system to trace murine skeletal muscle differentiation. Either a secreted bioluminescent reporter (Metridia luciferase) or a fluorescent reporter (green fluorescent protein [GFP]) was placed under the control of the truncated muscle creatine kinase (MCK) basal promoter enhanced by variable numbers of upstream MCK E-boxes. The engineered pE3MCK vector, coding a triple tandem of E-Boxes and the truncated MCK promoter, showed twentyfold higher levels of luciferase activation compared with a Cytomegalovirus (CMV) promoter. This newly developed reporter system allowed noninvasive monitoring of myogenic differentiation in a straining bioreactor. Additionally, binding sequences of endogenous microRNAs (miRNAs; seed sequences) that are known to be downregulated in myogenesis were ligated as complementary seed sequences into the reporter vector to reduce nonspecific signal background. The insertion of seed sequences improved the signal-to-noise ratio up to 25% compared with pE3MCK. Due to the highly specific, fast, and convenient expression analysis for cells undergoing myogenic differentiation, this reporter system provides a powerful tool for application in skeletal muscle tissue engineering.

  12. Proteomic Profiling of Mitochondrial Enzymes during Skeletal Muscle Aging

    Directory of Open Access Journals (Sweden)

    Lisa Staunton

    2011-01-01

    Full Text Available Mitochondria are of central importance for energy generation in skeletal muscles. Expression changes or functional alterations in mitochondrial enzymes play a key role during myogenesis, fibre maturation, and various neuromuscular pathologies, as well as natural fibre aging. Mass spectrometry-based proteomics suggests itself as a convenient large-scale and high-throughput approach to catalogue the mitochondrial protein complement and determine global changes during health and disease. This paper gives a brief overview of the relatively new field of mitochondrial proteomics and discusses the findings from recent proteomic surveys of mitochondrial elements in aged skeletal muscles. Changes in the abundance, biochemical activity, subcellular localization, and/or posttranslational modifications in key mitochondrial enzymes might be useful as novel biomarkers of aging. In the long term, this may advance diagnostic procedures, improve the monitoring of disease progression, help in the testing of side effects due to new drug regimes, and enhance our molecular understanding of age-related muscle degeneration.

  13. Maturação das vértebras cervicais e sua correlação com a idade óssea da mão e punho como indicadores no tratamento ortodôntico Cervical vertebral maturation and the correlation between the skeletal age of the hand-wrist as orthodontic treatment indicators

    Directory of Open Access Journals (Sweden)

    Vitoria Aparecida Muglia Moscatiello

    2008-08-01

    Full Text Available OBJETIVOS: a proposta deste estudo prospectivo, transversal e multicêntrico foi correlacionar as alterações morfológicas das vértebras cervicais C2, C3 e C4, com a idade cronológica e comparar com a idade esqueletal dos ossos da mão e punho; e verificar se existem diferenças no padrão de crescimento ósseo entre os gêneros masculino e feminino. METODOLOGIA: a amostra foi constituída por 140 pacientes, 74 do gênero feminino e 66 do masculino. A avaliação das alterações das vértebras cervicais foi feita pelo método de Hassel e Farman modificado por Baccetti, Franchi e McNamara para 5 estágios que se correlacionam com o crescimento puberal em telerradiografias cranianas em norma lateral. As radiografias da mão e punho avaliaram os eventos de ossificação por meio do método de Greulich e Pyle. RESULTADOS: os resultados demonstraram correlação dos estágios de maturação das vértebras cervicais com a idade cronológica; e correlação positiva e moderada, estatisticamente significante entre os dois métodos com r = 0,6326 (IC = 95% e p AIM: The aim of this prospective, transversal, multicentric study was to determine the correlation between the morphologic changes of the second, third and fourth cervical vertebral bodies and the chronological age; to compare with the skeletal age of the hand and wrist bones; and to verify the differences in the bone growth pattern between male and female. METHODS: The sample was constituted by 140 subjects, 74 girls and 66 boys. The morphologic alterations of the cervical vertebrae was analyzed by the Hassel and Farman method modified by Baccetti, Franchi and McNamara to 5 stages that correlate to the puberal growth in lateral cephalometric radiographs. The hand-wrist radiographs evaluated the events of ossification by the method of Greulich and Pyle. RESULTS: The results demonstrated: correlation of the stages of cervical vertebral maturation with the chronological age; positive and

  14. A case of lethal congenital dwarfism with accelerated skeletal maturation

    International Nuclear Information System (INIS)

    Blomstrand, S.; Claesson, I.; Saeve-Soederbergh, J.

    1985-01-01

    Details of a female infant, who was born after 29 weeks gestation and who died within minutes of birth, are presented. The infant was hydropic, showed macroglossia and had very short limbs with normal sized hands and feet. Apart from a preductal aortic coarctation the pathological findings were confined to the skeleton. The radiographical and histological findings are described in detail; they differ from those of previous studies of similar conditions. (orig.)

  15. Case of lethal congenital dwarfism with accelerated skeletal maturation

    Energy Technology Data Exchange (ETDEWEB)

    Blomstrand, S.; Claesson, I.; Saeve-Soederbergh, J.

    1985-02-01

    Details of a female infant, who was born after 29 weeks gestation and who died within minutes of birth, are presented. The infant was hydropic, showed macroglossia and had very short limbs with normal sized hands and feet. Apart from a preductal aortic coarctation the pathological findings were confined to the skeleton. The radiographical and histological findings are described in detail; they differ from those of previous studies of similar conditions.

  16. Antioxidant activity and phenol content of extracts of bark, stems, and young and mature leaves from Blepharocalyx salicifolius (Kunth O. Berg

    Directory of Open Access Journals (Sweden)

    E. Habermann

    Full Text Available Abstract Phenolic compounds are a group of plant secondary metabolites known to have a variety of bioactivities, including the ability to function as antioxidants. Because of the side effects of the use of synthetic substances, the search for natural and less toxic compounds has increased significantly. This study was designed to evaluate the antioxidant activity and phenol content of hexane, ethyl acetate, and aqueous extracts of the bark (suber and stems as well as the young and mature leaves of Blepharocalyx salicifolius. The extracts were obtained by extraction with organic solvents and subsequent fractionation by chromatographic partition coefficient. Preliminary tests for the presence of antioxidants were performed using bioautography in thin-layer chromatography. The antioxidant activity of the extracts was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH method, and the phenol content of the extracts was quantified using the Folin-Ciocalteu technique. The results showed that 9 of the 12 extracts evaluated displayed very strong antioxidant activity and three displayed moderate activity. Aqueous extracts of the young leaves and bark and the ethyl acetate extract of the young leaves showed the highest levels of antioxidant activity and total phenolic content (TPC. A correlation was observed between TPC and antioxidant activity index (AAI with a correlation coefficient (r2 of 0.7999. Thus, the high phenol content of B. salicifolius extracts and its correlation with antioxidant activity provide substrates for further studies.

  17. Seizure induces activation of multiple subtypes of neural progenitors and growth factors in hippocampus with neuronal maturation confined to dentate gyrus

    Energy Technology Data Exchange (ETDEWEB)

    Indulekha, Chandrasekharan L.; Sanalkumar, Rajendran [Neuro Stem Cell Biology Laboratory, Department of Neurobiology, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala 695 014 (India); Thekkuveettil, Anoopkumar [Molecular Medicine, Biomedical Technology Wing, Sree Chitra Thirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala (India); James, Jackson, E-mail: jjames@rgcb.res.in [Neuro Stem Cell Biology Laboratory, Department of Neurobiology, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala 695 014 (India)

    2010-03-19

    Adult hippocampal neurogenesis is altered in response to different physiological and pathological stimuli. GFAP{sup +ve}/nestin{sup +ve} radial glial like Type-1 progenitors are considered to be the resident stem cell population in adult hippocampus. During neurogenesis these Type-1 progenitors matures to GFAP{sup -ve}/nestin{sup +ve} Type-2 progenitors and then to Type-3 neuroblasts and finally differentiates into granule cell neurons. In our study, using pilocarpine-induced seizure model, we showed that seizure initiated activation of multiple progenitors in the entire hippocampal area such as DG, CA1 and CA3. Seizure induction resulted in activation of two subtypes of Type-1 progenitors, Type-1a (GFAP{sup +ve}/nestin{sup +ve}/BrdU{sup +ve}) and Type-1b (GFAP{sup +ve}/nestin{sup +ve}/BrdU{sup -ve}). We showed that majority of Type-1b progenitors were undergoing only a transition from a state of dormancy to activated form immediately after seizures rather than proliferating, whereas Type-1a showed maximum proliferation by 3 days post-seizure induction. Type-2 (GFAP{sup -ve}/nestin{sup +ve}/BrdU{sup +ve}) progenitors were few compared to Type-1. Type-3 (DCX{sup +ve}) progenitors showed increased expression of immature neurons only in DG region by 3 days after seizure induction indicating maturation of progenitors happens only in microenvironment of DG even though progenitors are activated in CA1 and CA3 regions of hippocampus. Also parallel increase in growth factors expression after seizure induction suggests that microenvironmental niche has a profound effect on stimulation of adult neural progenitors.

  18. Proteomics of Skeletal Muscle

    DEFF Research Database (Denmark)

    Deshmukh, Atul

    2016-01-01

    , of altered protein expressions profiles and/or their posttranslational modifications (PTMs). Mass spectrometry (MS)-based proteomics offer enormous promise for investigating the molecular mechanisms underlying skeletal muscle insulin resistance and exercise-induced adaptation; however, skeletal muscle......Skeletal muscle is the largest tissue in the human body and plays an important role in locomotion and whole body metabolism. It accounts for ~80% of insulin stimulated glucose disposal. Skeletal muscle insulin resistance, a primary feature of Type 2 diabetes, is caused by a decreased ability...... of muscle to respond to circulating insulin. Physical exercise improves insulin sensitivity and whole body metabolism and remains one of the most promising interventions for the prevention of Type 2 diabetes. Insulin resistance and exercise adaptations in skeletal muscle might be a cause, or consequence...

  19. Sustaining Exploration in Mature Basins

    International Nuclear Information System (INIS)

    Bayo, A.

    2002-01-01

    Exploration is a business like any other business driven by opportunity, resources and expectation of profit. Therefore, exploration will thrive anywhere the opportunities are significant, the resources are available and the outlook for profit (or value creation) is good. To sustain exploration activities anywhere, irrespective of the environment, there must be good understanding of the drivers of these key investment criteria. This paper will examine these investment criteria as they relate to exploration business and address the peculiarity of exploration in mature basin. Mature basins are unique environment that lends themselves a mix of fears, paradigms and realities, particularly with respect to the perception of value. To sustain exploration activities in a mature basin, we need to understand these perceptions relative to the true drivers of profitability. Exploration in the mature basins can be as profitable as exploration in emerging basins if the dynamics of value definition-strategic and fiscal values are understood by operators, regulators and co ventures alike. Some suggestions are made in this presentation on what needs to be done in addressing these dynamic investment parameters and sustaining exploration activities in mature basins