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Sökning: WFRF:(Boonen Steven)

  • Resultat 61-69 av 69
  • Föregående 123456[7]
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61.
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62.
  • Venken, Katrien, et al. (författare)
  • Bone and muscle protective potential of the prostate-sparing synthetic androgen 7alpha-methyl-19-nortestosterone: evidence from the aged orchidectomized male rat model.
  • 2005
  • Ingår i: Bone. - 8756-3282. ; 36:4, s. 663-70
  • Tidskriftsartikel (refereegranskat)abstract
    • This study reports the preclinical evaluation of the bone and muscle protective potential of the synthetic androgen 7alpha-methyl-19-nortestosterone (MENTtrade mark), as assessed in the aged orchidectomized rat model. Aged (13-month-old) orchidectomized Wistar rats were treated with different doses of MENT (4, 12 or 36 microg/day) subcutaneously for 16 weeks via mini-osmotic pumps. Analysis of the effects of androgen deficiency versus MENT replacement was performed using quantitative computed tomography (pQCT), dual energy X-ray absorptiometry (DEXA) and biochemical markers of bone turnover. At the end of the study period, prostate weight in orchidectomized rats treated with low- (4 microg/day) or mid-dose (12 mug/day) MENT remained significantly lower compared to the sham-operated animals (-47% and -25%, respectively). High-dose MENT (36 microg/day), on the other hand, induced prostate hypertrophy (+21% versus sham). Low-, mid- and high-dose MENT were found to be effective in suppressing the acceleration of bone remodeling following orchidectomy, as assessed by osteocalcin and deoxypyridinoline. In addition, low-, mid- and high-dose were able to prevent the orchidectomy-induced bone loss, as evaluated by DEXA at the femur and total-body and by pQCT at the femur. Compared to sham-operated animals, the low- and mid-dose MENT groups showed no decline in lean body mass and no muscle atrophy (as measured by m. quadriceps weight) at 16 weeks, whereas high-dose MENT was associated with a significant decline in lean body mass (-8.5% versus sham) and quadriceps weight (-10.6%). We conclude that, in the aged orchidectomized rat model, low- and mid-doses of the synthetic androgen MENT have bone and muscle protective effects and do not induce prostate hypertrophy. The bone protective action of high-dose MENT, however, occurs at the expense of muscle wasting and prostate hypertrophy. Our findings support the need for human studies to explore the potential of MENT as an option for androgen replacement in aging men.
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63.
  • Venken, Katrien, et al. (författare)
  • Growth without growth hormone receptor: estradiol is a major growth hormone-independent regulator of hepatic IGF-I synthesis.
  • 2005
  • Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - 0884-0431. ; 20:12, s. 2138-49
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of estrogens in the regulation of pubertal growth independently of GH and its receptor was studied in male mice with disrupted GHRKO. E(2) rescued skeletal growth rates in GHRKO associated with an increase in hepatic and serum IGF-I. These data show that E(2) rescues pubertal growth during GH resistance through a novel mechanism of GHR-independent stimulation of hepatic IGF-I production. INTRODUCTION: Growth hormone (GH) and estrogen play a pivotal role in pubertal growth and bone mineral acquisition. Estrogens can affect GH secretion and thereby provide a GH-dependent mechanism for their effects on skeletal growth. It is presently unclear if or to what extent estrogens are able to regulate pubertal growth and bone mineral accrual independently of GH and its receptor. MATERIALS AND METHODS: Estradiol (E(2); 0.03 mug/day by subcutaneous silastic implants) was administered to orchidectomized (ORX) male mice with disrupted GHR (GHRKO) and corresponding WTs during late puberty (6-10 weeks). Longitudinal and radial bone growth, IGF-I in serum and its expression in liver, muscle, and bone, and liver gene expression were studied by histomorphometry, RIA, RT-PCR, microarrays, and Western blotting, respectively. RESULTS: E(2) stimulated not only longitudinal (femur length and growth plate thickness) and radial growth (cortical thickness and periosteal perimeter), but also rescued longitudinal and periosteal growth rates in ORX GHRKO, whereas no significant changes occurred in WT. E(2) thereby upregulated serum IGF-I and liver IGF-I synthesis (+21% and +52%, respectively) in ORX GHRKO, whereas IGF-I synthesis in femur or muscle was unaffected. Study of the underlying mechanism of the stimulation of hepatic IGF-I expression showed that E(2) restored downregulated receptor signaling systems, such as the estrogen receptor alpha and the prolactin receptor. E(2) thereby recovered the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway as evidenced by a significantly increased activation of the transcription factor STAT5 in ORX GHRKO. CONCLUSIONS: Our data show a stimulation of skeletal growth through upregulation of hepatic IGF-I by a hormone other than GH. E(2) rescues pubertal skeletal growth during GH resistance through a novel mechanism of GHR-independent stimulation of IGF-I synthesis in the liver.
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64.
  • Venken, Katrien, et al. (författare)
  • Impact of androgens, growth hormone, and IGF-I on bone and muscle in male mice during puberty.
  • 2007
  • Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - 0884-0431. ; 22:1, s. 72-82
  • Tidskriftsartikel (refereegranskat)abstract
    • The interaction between androgens and GH/IGF-I was studied in male GHR gene disrupted or GHRKO and WT mice during puberty. Androgens stimulate trabecular and cortical bone modeling and increase muscle mass even in the absence of a functional GHR. GHR activation seems to be the main determinant of radial bone expansion, although GH and androgens are both necessary for optimal stimulation of periosteal growth during puberty. INTRODUCTION: Growth hormone (GH) is considered to be a major regulator of postnatal skeletal growth, whereas androgens are considered to be a key regulator of male periosteal bone expansion. Moreover, both androgens and GH are essential for the increase in muscle mass during male puberty. Deficiency or resistance to either GH or androgens impairs bone modeling and decreases muscle mass. The aim of the study was to investigate androgen action on bone and muscle during puberty in the presence and absence of a functional GH/insulin-like growth factor (IGF)-I axis. MATERIALS AND METHODS: Dihydrotestosterone (DHT) or testosterone (T) were administered to orchidectomized (ORX) male GH receptor gene knockout (GHRKO) and corresponding wildtype (WT) mice during late puberty (6-10 weeks of age). Trabecular and cortical bone modeling, cortical strength, body composition, IGF-I in serum, and its expression in liver, muscle, and bone were studied by histomorphometry, pQCT, DXA, radioimmunoassay and RT-PCR, respectively. RESULTS: GH receptor (GHR) inactivation and low serum IGF-I did not affect trabecular bone modeling, because trabecular BMD, bone volume, number, width, and bone turnover were similar in GHRKO and WT mice. The normal trabecular phenotype in GHRKO mice was paralleled by a normal expression of skeletal IGF-I mRNA. ORX decreased trabecular bone volume significantly and to a similar extent in GHRKO and WT mice, whereas DHT and T administration fully prevented trabecular bone loss. Moreover, DHT and T stimulated periosteal bone formation, not only in WT (+100% and +100%, respectively, versus ORX + vehicle [V]; p < 0.05), but also in GHRKO mice (+58% and +89%, respectively, versus ORX + V; p < 0.05), initially characterized by very low periosteal growth. This stimulatory action on periosteal bone resulted in an increase in cortical thickness and occurred without any treatment effect on serum IGF-I or skeletal IGF-I expression. GHRKO mice also had reduced lean body mass and quadriceps muscle weight, along with significantly decreased IGF-I mRNA expression in quadriceps muscle. DHT and T equally stimulated muscle mass in GHRKO and WT mice, without any effect on muscle IGF-I expression. CONCLUSIONS: Androgens stimulate trabecular and cortical bone modeling and increase muscle weight independently from either systemic or local IGF-I production. GHR activation seems to be the main determinant of radial bone expansion, although GHR signaling and androgens are both necessary for optimal stimulation of periosteal growth during puberty.
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65.
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66.
  • Wardlaw, Douglas, et al. (författare)
  • Balloon kyphoplasty in patients with osteoporotic vertebral compression fractures
  • 2012
  • Ingår i: Expert Review of Medical Devices. - : Expert Reviews. - 1745-2422. ; 9:4, s. 423-436
  • Forskningsöversikt (refereegranskat)abstract
    • Balloon kyphoplasty (BKP) is a minimally invasive surgical procedure indicated for treatment of painful vertebral compression fractures. During BKP, cannulae are placed percutaneously into the vertebral body, allowing insertion of inflatable balloons. Inflating the balloons partially restores vertebral body height, compacts the bone and creates a cavity for placement of bone cement after balloon removal. Placement of the cement reduces and stabilizes the fracture. BKP differs from vertebroplasty in that it aims to restore vertebral height and reduce kyphotic deformity. Case reports and observational studies have consistently shown that BKP significantly reduces pain, increases mobility and functional capacity and improves quality of life for up to 3 years. Clinically significant adverse events have been rarely reported. These findings were confirmed in randomized and nonrandomized prospective controlled studies. The objective of this review is to describe the surgical procedures involved in BKP and to review the evidence supporting its use.
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67.
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68.
  • Wu, Frederick C W, et al. (författare)
  • Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: The European Male Aging Study
  • 2008
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 1945-7197. ; 93:7, s. 2737-2745
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT The cause of declining testosterone (T) in aging men and their relationships with risk factors are unclear. OBJECTIVE To investigate the relationships between lifestyle and health with reproductive hormones in aging men. DESIGN Baseline cross-sectional survey on 3200 community - dwelling men aged 40 - 79 yr from a prospective cohort study in 8 European countries. RESULTS Four predictors were associated with distinct modes of altered function:- Age: lower free T (FT) (-3.12 pmol/L/ yr, p<0.001) with raised luteinizing hormone (LH) suggesting impaired testicular function. Obesity: lower total T (TT) (-2.32 nmol/L) and FT (-17.60 pmol/L) for BMI >/=25 - <30 kg/m(2) and lower TT (-5.09 nmol/L,) and FT (-53.72 pmol/L) for BMI >/=30 kg/m(2) (p <0.001 - 0.01, referent: BMI <25 kg/m(2)) with unchanged/decreased LH, indicating hypothalamus/pituitary dysfunction. Co-morbidity: lower TT (-0.80 nmol/L, p <0.01) with unchanged LH in younger men but higher LH in older men. Smoking: higher sex hormone binding globulin (SHBG) (5.96 nmol/L, p <0.001) and LH (0.77 U/L, p <0.01) with increased TT (1.31 nmol/L, p<0.001) but not FT, compatible with a resetting of T-LH negative feedback due to elevated SHBG. CONCLUSIONS Complex multiple alterations in the hypothalamic-pituitary-testicular axis function exist in ageing men against a background of progressive age-related testicular impairment. These changes are differentially linked to specific risk factors. Some risk factors operate independently of but others interact with age, in contributing to the T decline. These potentially modifiable risk factors suggest possible preventative measures to maintain T during in aging men.
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69.
  • Wu, Frederick C. W., et al. (författare)
  • Identification of Late-Onset Hypogonadism in Middle-Aged and Elderly Men
  • 2010
  • Ingår i: 88th Annual Meeting of the Endocrine-Society,2006-06-24 - 2006-06-27. - : Massachusetts Medical Society. ; 363:2, s. 123-135
  • Konferensbidrag (refereegranskat)abstract
    • BACKGROUND The association between aging-related testosterone deficiency and late-onset hypogonadism in men remains a controversial concept. We sought evidence-based criteria for identifying late-onset hypogonadism in the general population on the basis of an association between symptoms and a low testosterone level. METHODS We surveyed a random population sample of 3369 men between the ages of 40 and 79 years at eight European centers. Using questionnaires, we collected data with regard to the subjects' general, sexual, physical, and psychological health. Levels of total testosterone were measured in morning blood samples by mass spectrometry, and free testosterone levels were calculated with the use of Vermeulen's formula. Data were randomly split into separate training and validation sets for confirmatory analyses. RESULTS In the training set, symptoms of poor morning erection, low sexual desire, erectile dysfunction, inability to perform vigorous activity, depression, and fatigue were significantly related to the testosterone level. Increased probabilities of the three sexual symptoms and limited physical vigor were discernible with decreased testosterone levels (ranges, 8.0 to 13.0 nmol per liter [2.3 to 3.7 ng per milliliter] for total testosterone and 160 to 280 pmol per liter [46 to 81 pg per milliliter] for free testosterone). However, only the three sexual symptoms had a syndromic association with decreased testosterone levels. An inverse relationship between an increasing number of sexual symptoms and a decreasing testosterone level was observed. These relationships were independently confirmed in the validation set, in which the strengths of the association between symptoms and low testosterone levels determined the minimum criteria necessary to identify late-onset hypogonadism. CONCLUSIONS Late-onset hypogonadism can be defined by the presence of at least three sexual symptoms associated with a total testosterone level of less than 11 nmol per liter (3.2 ng per milliliter) and a free testosterone level of less than 220 pmol per liter (64 pg per milliliter).
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  • Resultat 61-69 av 69
  • Föregående 123456[7]
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