RESUMO
Background During the transition phase (TP), patients with growth hormone deficiency (GHD) exhibit decreased muscle strength. Studies assessing the effects of resistance exercise alone on muscle strength in these individuals are scarce. The objective of this study was to evaluate the effects of a program of resistance exercise (PRE) on parameters of muscle strength in subjects in the TP and with childhood-onset GHD treated with recombinant GH (rGH). Methods Sixteen male patients were enrolled and divided into two groups: GHD (n=9) and GH sufficiency (GHS, n=7). Patients with GHD underwent a 12-week PRE followed by another 12-week PRE plus rGH, while GHS patients underwent a 12-week PRE alone. Dynamic knee muscle strength was evaluated using an isokinetic dynamometer. Results Before PRE, there were significant differences between the groups regarding the results of flexor peak torque (FPT) normalized to body weight (BW-FPT) in the dominant (DO, p=0.008) and non-dominant (ND, p=0.01) limbs, and in the agonist/antagonist (A/A) ratio in the DO (p=0.02) and ND (p=0.006) limbs. After PRE in the GHD group, values of FPT and BW-FPT in both limbs increased significantly (p<0.001) and independently of rGH, while the A/A ratio value improved significantly (p<0.001) in the ND limb. Conclusions A short period of PRE alone was sufficient to improve parameters of muscle strength in young male adults with childhood-onset GHD.
Assuntos
Nanismo Hipofisário/terapia , Terapia por Exercício/métodos , Hormônio do Crescimento Humano/deficiência , Força Muscular/fisiologia , Treinamento Resistido , Adolescente , Adulto , Composição Corporal , Peso Corporal , Nanismo Hipofisário/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: A model for in vivo gene therapy based on electroporation of human growth hormone (hGH)-coding naked DNA in the muscle of dwarf (lit/lit) and immunodeficient dwarf (lit/scid) mice is described. METHODS: A plasmid containing the ubiquitin C promoter and the genomic hGH sequence was administered to the exposed quadriceps muscle, followed by electrotransfer using eight 50-V pulses of 20 ms at a 0.5-s interval. Serum hGH levels were determined after various days of DNA administration and a long-term body weight gain experiment was carried out. RESULTS: Serum hGH, determined 3 days after DNA administration, revealed a significant dose-response curve (p < 0.01) in the 0-50 microg range. Because 50 microg of plasmid DNA produced circulating hGH levels of 2-3 ng/ml for at least 12 days, a long-term body weight gain assay was carried out. After 60 days, the weight of treated lit/scid mice increased 33.1% compared to a 4.2% weight decrease for the control group. hGH circulating levels were of the order of 1.5-3 ng/ml throughout the experiment and the average weight increase during the first 10 days was comparable to that obtained upon regular daily injection of 10 microg of recombinant hGH per mouse, producing comparable circulating levels of the hormone. A lower, but still significant increase in body weight was obtained upon repeating the experiment in immunocompetent dwarf mice (lit/lit). CONCLUSIONS: We report for the first time sustained levels of circulating hGH after intramuscular naked DNA administration and, consequently, a highly significant weight increase of dwarf 'little' mice.
Assuntos
Modelos Animais de Doenças , Nanismo Hipofisário/terapia , Terapia Genética , Hormônio do Crescimento Humano/metabolismo , Hormônio do Crescimento Humano/uso terapêutico , Plasmídeos/genética , Animais , Peso Corporal , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Músculos/patologia , Tamanho do Órgão , Fenótipo , Fatores de TempoRESUMO
A gene therapy clinical trial for treatment of growth hormone (GH) deficiency has not been reached yet, but several strategies using different gene transfer methodologies and animal models have been developed and showed successful results. We have set up an ex vivo gene therapy protocol using primary human keratinocytes transduced with an efficient retroviral vector (LXSN) encoding the human (hGH) or mouse GH (mGH) genes. These stably modified cells presented high in vitro expression levels of hGH (7 microg/106 cells/d) and mGH (11 microg/106 cells/d) after selection with geneticin. When the hGH-secreting keratinocytes were grafted onto immunodeficient dwarf mice (lit/scid), hGH levels in the circulation were about 0.2-0.3 ng/mL during a 12-d assay and these animals presented a significant body weight increase (p < 0.01) compared to the control. Substitution of conventional grafting methodologies with organotypic raft cultures revealed a peak value of up to 20 ng mGH/mL in the circulation of grafted lit/scid mice at 1 h postimplantation, followed by a rapid decline to baseline (approximately 2 ng/mL) within 24 h. One week after grafting, however, the cultured excised implants still presented approx 45% of their original in vitro secretion efficiency. Further studies are being carried out to identify the main factor(s) that still constitute one of the major impediments to the success of this promising model of cutaneous gene therapy.
Assuntos
Nanismo Hipofisário/terapia , Terapia Genética/métodos , Hormônio do Crescimento/genética , Hormônio do Crescimento/metabolismo , Queratinócitos/transplante , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Retroviridae/genética , Pele/citologia , Transdução GenéticaRESUMO
We are introducing a patient of 22 years old who suffers from Dwarfness and primary Amenorrhea. She showed dosages of basal somatotrophin and post estimulation of 0.5 ng/ml or less, somatomedin (IGF1): 2.40 ui/ml, rudiment uterus and annexes with normal karyotype 46xx. RMN of Sella Turcica and adjacencies showed; a posterior pituitary lobe ectopy, with the conservation of his hypothalamic conexion and hormonal deficit of L.A. (suprarenal, gonadal and somatotrophic axes). The use of RMN allowed us to evaluate and thus reached a precise diagnosis in reference to the hypothalamic lesion.
Assuntos
Humanos , Feminino , Adulto , Amenorreia , Nanismo Hipofisário , Nanismo Hipofisário/diagnóstico , Nanismo Hipofisário/terapia , Neuro-Hipófise/anormalidades , Glândula Tireoide/fisiopatologia , Hipopituitarismo/congênito , Diabetes Insípido , Hormônio do Crescimento/uso terapêutico , Hidrocortisona/uso terapêutico , Tiroxina/uso terapêuticoRESUMO
We are introducing a patient of 22 years old who suffers from Dwarfness and primary Amenorrhea. She showed dosages of basal somatotrophin and post estimulation of 0.5 ng/ml or less, somatomedin (IGF1): 2.40 ui/ml, rudiment uterus and annexes with normal karyotype 46xx. RMN of Sella Turcica and adjacencies showed; a posterior pituitary lobe ectopy, with the conservation of his hypothalamic conexion and hormonal deficit of L.A. (suprarenal, gonadal and somatotrophic axes). The use of RMN allowed us to evaluate and thus reached a precise diagnosis in reference to the hypothalamic lesion. (AU)
Assuntos
Humanos , Feminino , Adulto , Nanismo Hipofisário/diagnóstico , Nanismo Hipofisário/terapia , Nanismo Hipofisário/diagnóstico por imagem , Hipopituitarismo/congênito , Neuro-Hipófise/anormalidades , Glândula Tireoide/fisiopatologia , Amenorreia , Diabetes Insípido , Tiroxina/uso terapêutico , Hidrocortisona/uso terapêutico , Hormônio do Crescimento/uso terapêuticoRESUMO
Analisam-se um grupo de pacientes com deficiência de hormônio do crescimento (DHC), incluidos no Programa do Hormônio do Crescimento do INAMPS-RS, do Hospital Materno Infantil Presidente Vargas (HMIPV). Estes pacientes submeteram-se ao tratamento com o hormônio do crescimento (HC) por um período médio de três e meio a quatro anos. Foram estudados a prevalência de sexo, etiologia e classificaçäo da DHC. Deste grupo inicial, doze crianças foram avaliadas separadamente, a fim de um estudo mais acurado das condiçöes de nascimento e do crescimento antes e após o tratamento com HC. Junta-se a estes dados uma revisäo da literatura