| 1. |
- Ljunggren, Östen, et al.
(författare)
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Allele-Specific Gene Silencing in Osteogenesis Imperfecta
- 2011
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Ingår i: Cartilage and Bone Development and Its Disorders. - : S. Karger AG. - 9783805597920 ; 21, s. 85-90
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Konferensbidrag (refereegranskat)abstract
- OI is caused by mutations in the genes encoding for collagen type I COL1A1 and COL1A2, respectively. The patients suffer from bone fragility, and the severity can range from mild, with fractures in the youth, to lethal forms. Today, there is no effective treatment for the disorder. OI is caused by dominant negative mutations. A tempting approach to treat the disease would be to silence the allele carrying the mutation. This could in theory be done with siRNAs. Today, more than 800 various mutations are reported, and to create siRNA against a specific mutation is difficult. Instead, by developing siRNA against common polymorphic variations, it would be possible to silence the mutation by a standardized method regardless where the mutation is located on the allele. If the concept of allele-specific gene silencing by inhibitory RNA directed towards dominant negative mutations could be proven, this might be a novel approach to gene therapy in OI.
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| 2. |
- Norjavaara, Ensio, 1954, et al.
(författare)
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Sex Steroid Replacement Therapy in Female Hypogonadism from Childhood to Young Adulthood.
- 2016
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Ingår i: Endocrine development. - : S. Karger AG. - 1662-2979 .- 1421-7082. ; 29, s. 198-213
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Tidskriftsartikel (refereegranskat)abstract
- The overall goal of pubertal sex hormone replacement therapy (HRT) in girls is not only about development of secondary sexual characteristics, but also to establish an adult endocrine and metabolic milieu, as well as adult cognitive function. Estradiol (E2) is the first choice for HRT compared to ethinyl estradiol (EE2). E2 is the most potent endogenous estrogen in the circulation, with established levels during spontaneous puberty. Transdermal E2, compared to oral administration, is the first choice to start pubertal HRT. Transdermal application avoids liver exposure to supraphysiologic estrogen concentrations and provides a more physiologic mechanism for hormone delivery. By cutting E2 matrix patches in doses of 0.05-0.07 µg/kg or administrate E2 gel in doses of 0.1 mg/day, serum concentrations of E2 seen in early spontaneous puberty can be obtained. Patches can be removed in the morning and thereby mimic the normal circadian rhythm. For those clinics with access to sensitive E2 determinations methods (extraction followed by radioimmunoassay or mass spectrometry) monitoring the attained E2 serum levels is recommended in order to optimally mimic the levels seen in early puberty as well as growth velocity, breast and uterus development. Mid- and late pubertal HRT is obtained by increased doses of E2, adding cyclic oral or transdermal progestin, as well as testosterone gel over the pubic area if indicated.
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| 4. |
- Isgaard, Jörgen, 1959
(författare)
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Ghrelin and the cardiovascular system.
- 2013
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Ingår i: The Ghrelin System. Eds: Benso A.; Casanueva F.F.;Granata R.. - : Karger. - 1662-2979. - 9783805599085 ; 25, s. 83-90
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Bokkapitel (refereegranskat)abstract
- Although ghrelin was initially associated with regulation of appetite, the cardiovascular system has also been recognized as a potentially important target for its effects. Moreover, experimental and a limited number of clinical studies suggest a potential role for ghrelin in the treatment of congestive heart failure. So far, reported cardiovascular effects of growth hormone secretagogues and/or ghrelin include lowering of peripheral resistance, either direct at the vascular level and/or by modulating sympathetic nervous activity. Other observed effects indicate possible improvement of contractility and cardioprotective and anti-inflammatory effects both in vivo and in vitro. Taken together, these results offer an interesting perspective on the future where further studies aiming at evaluating a role of growth hormone secretagogues and ghrelin in the treatment of cardiovascular disease are warranted.
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| 5. |
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| 6. |
- Johansson, Therése, et al.
(författare)
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Very long-term follow-up of girls with early and late menarche
- 2005
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Ingår i: Abnormalities in puberty. - Basel : Karger. - 9783805578677 - 3805578679 ; 8, s. 126-136
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Short- and long-term psychosocial effects of precocious or early normal puberty are probably more important for individuals than the moderate losses in final height they experience. Despite this, pediatric endocrinologists have focused much more on final height than psychosocial outcomes. As a surrogate for long-term follow-up studies of girls with precocious puberty, we have reviewed the results of a very long-term study of physical and psychosocial development of girls with normal early puberty. Results revealed that at age 15-16, girls with menarche before age 11 (early) were more norm-breaking, including being delinquents. In addition, they had earlier advanced sexual experiences. By adult age, there were no differences in psychosocial adjustment between the early- and late-developed women. Thus, the effects of early pubertal timing for psychosocial problems seem to be adolescent-limited. At ages 27 and 43, early-developed women had lower academic education. Regarding somatic development, at age 43, women with early menarche were shorter and heavier, had worse physical fitness and dieted more frequently compared to other women. There was no difference in quality of life. In searching for reasons for the antisocial behaviors in adolescence and the lower educational levels among early developers, early heterosexual relations seem to be the most crucial.
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| 11. |
- Menzies, John R W, et al.
(författare)
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Ghrelin, reward and motivation.
- 2013
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Ingår i: Endocrine development. - : S. Karger AG. - 1662-2979. ; 25, s. 101-11
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Forskningsöversikt (refereegranskat)abstract
- Almost all circulating gut peptides contribute to the control of food intake by signalling satiety. One important exception is ghrelin, the only orexigenic peptide hormone thus far described. Ghrelin secretion increases before meals and behavioural and electrophysiological evidence shows that ghrelin acts in the hypothalamus via homeostatic pathways to signal hunger and increase food intake and adiposity. These findings strongly suggest that ghrelin is a dynamically regulated peripheral hunger signal. However, ghrelin also interacts with the brain reward pathways to increase food intake, alter food preference and enhance food reward. Here we discuss ghrelin's role as an endocrine gut-brain reward signal in relation to homeostatic and hedonic feeding control.
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| 17. |
- Vanderschueren, Dirk, et al.
(författare)
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Reversing sex steroid deficiency and optimizing skeletal development in the adolescent with gonadal failure.
- 2005
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Ingår i: Endocrine development. - Basel : KARGER. - 1421-7082. ; 8, s. 150-65
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Tidskriftsartikel (refereegranskat)abstract
- During puberty, the acquisition of skeletal mass and areal bone mineral density (BMD) mainly reflects an increase in bone size (length and perimeters) and not true volumetric BMD. Sexual dimorphism in bone mass and areal BMD is also explained by differences in bone size (longer and wider bones in males) and not by differences in volumetric BMD. Androgens stimulate skeletal growth by activation of the androgen receptor, whereas estrogens (following aromatization of androgens and stimulation of estrogen receptors) have a biphasic effect on skeletal growth during puberty. Recent evidence from clinical cases has shown that many of the growth-promoting effects of the sex steroids are mediated through estrogens rather than androgens. In addition, skeletal maturation and epiphyseal fusion are also estrogen-dependent in both sexes. Nevertheless, independent actions of androgens in these processes also occur. Both sex steroids maintain volumetric BMD during puberty. Androgens interact with the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis neonatally, resulting in a sexual dimorphic GH pattern during puberty, whereas estrogens stimulate GH and hereby IGF-I in both sexes. Hypogonadism in adolescents impairs not only bone size but also maintenance of volumetric BMD, hereby severely reducing peak areal BMD. Delayed puberty in boys and Turner's syndrome in women impair both bone length and size, reducing areal BMD. Whether volumetric BMD is also reduced and whether fracture risk is increased in these conditions remains controversial. Replacing sex steroids according to a biphasic pattern (starting at low doses and ending at high-normal doses) seems the safest approach to reach targeted height and to optimize bone development.
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| 18. |
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| 19. |
- Åberg, N David, 1970
(författare)
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Role of the Growth Hormone/Insulin-Like Growth Factor 1 Axis in Neurogenesis
- 2010
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Ingår i: Pediatric Neuroendocrinology. Endocr Dev.. - 1421-7082. ; 17, s. 63-76
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Forskningsöversikt (refereegranskat)abstract
- The growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis is not only involved in brain growth, development and myelination, but also in brain plasticity as indexed by neurogenesis. This may have links to various cognitive effects of GH and IGF-1. GH and IGF-1 affect the genesis of neurons, astrocytes, endothelial cells and oligodendrocytes. Specifically, IGF-1 increases progenitor cell proliferation and numbers of new neurons, oligodendrocytes, and blood vessels in the dentate gyrus of the hippocampus. In the adult cerebral cortex IGF-1 only affects oligodendrogenesis. Recently, GH therapy has also been shown to induce cell genesis in the adult brain. The profile of effects by GH therapy may be somewhat different than that of IGF-1. In addition, GH secretagogues (GHS) also have neuroprotective and cell regenerative effects per se in the brain. Finally, transgenic disruptions in GH signaling pathways affect neuron and astrocyte cell numbers during development and during adulthood. Altogether, data suggest that both exogenous and endogenous GH and/or IGF-1 may be used as agents to enhance cell genesis and neurogenesis in the adult brain. Theoretically these substances could be used to enhance recovery after brain injuries. However, further experiments with specific animal models for brain injuries are needed before clinical trials can be started.
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