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1.
Yonsei Med J ; 61(4): 331-340, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32233176

RESUMO

PURPOSE: Osteoarthritis (OA) of the temporomandibular joint (TMJ) elicits cartilage and subchondral bone defects. Growth hormone (GH) promotes chondrocyte growth. The aim of this study was to evaluate the efficacy of intra-articular injections of GH to treat TMJ-OA. MATERIALS AND METHODS: Monosodium iodoacetate (MIA) was used to induce OA in the TMJs of rats. After confirming the induction of OA, recombinant human GH was injected into the articular cavities of rats. Concentrations of GH and IGF-1 were measured in the blood and synovial fluid, and OA grades of cartilage and subchondral bone degradation were recorded by histological examination and micro-computed tomography. RESULTS: MIA-induced OA in the rat TMJ upregulated insulin-like growth factor-1 (IGF-1) rather than GH levels. GH and IGF-1 concentrations were increased after local injection of GH, compared with controls. Locally injected GH lowered osteoarthritic scores in the cartilage and subchondral bone of the TMJ. CONCLUSION: Intra-articular injection of GH improved OA scores in rat TMJs in both cartilage and subchondral bone of the condyles without affecting condylar bone growth. These results suggest that intra-articular injection of human GH could be a suitable treatment option for TMJ-OA patients in the future.


Assuntos
Condrócitos/efeitos dos fármacos , Hormônio do Crescimento/administração & dosagem , Fator de Crescimento Insulin-Like I/administração & dosagem , Osteoartrite/tratamento farmacológico , Articulação Temporomandibular/efeitos dos fármacos , Idoso , Animais , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Hormônio do Crescimento/efeitos adversos , Hormônio do Crescimento Humano , Humanos , Injeções Intra-Articulares , Masculino , Osteoartrite/diagnóstico por imagem , Osteoartrite/patologia , Ratos , Líquido Sinovial , Articulação Temporomandibular/diagnóstico por imagem , Articulação Temporomandibular/fisiopatologia , Microtomografia por Raio-X
2.
Med. clín (Ed. impr.) ; 154(8): 289-294, abr. 2020. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-193198

RESUMO

ANTECEDENTES Y OBJETIVO: El tratamiento con hormona de crecimiento recombinante humana (rhGH) en niños nacidos pequeños para la edad gestacional (PEG) se ha mostrado eficaz, aunque con variedad en la respuesta. Se evalúa la talla adulta y los factores que determinan la respuesta a largo plazo. PACIENTES Y MÉTODOS: Estudio retrospectivo de 80 pacientes PEG tratados con rhGH por baja talla y seguidos hasta la talla adulta (23 varones). RESULTADOS: El grupo que inició el tratamiento antes de la pubertad alcanzó mayor talla adulta (−1,4±0,6 vs. −1,9±0,6 púberes). Existió mayor ganancia de talla en los tratados durante ≥ 2 años en prepubertad (1,32±0,5 SDE). Los factores asociados con una mayor ganancia de talla fueron: a) la menor talla, peso e IMC al inicio; b) la menor edad cronológica, ósea y el menor nivel de IGF-I iniciales; c) la mayor distancia con la talla genética; d) la mayor velocidad de crecimiento el primer y el segundo año y la mayor ganancia de talla previa y durante la pubertad. El porcentaje de buena respuesta en el primer año varió entre el 46,6 y el 81,6% en función del criterio empleado. El incremento de la velocidad de crecimiento≥3cm/año es el que mejor se relaciona con buena respuesta a largo plazo. CONCLUSIONES: El tratamiento con rhGH en niños PEG produce un incremento variable de talla adulta, que les permite alcanzar su rango genético. Los mejores resultados se producen en el grupo con mayor número de años en tratamiento en la prepubertad y no dependen de la respuesta hipofisaria de GH


BACKGROUND AND OBJECTIVE: Recombinant human growth hormone (rhGH) treatment in small for gestational age (SGA) children has been effective, although there is significant variability in the response. Adult height and the factors that determine the long-term response are evaluated. Patients and DESIGN: A retrospective study of 80 patients born SGA with short stature treated with rhGH and followed until adult height (23 males). RESULTS: The group starting treatment pre-puberty reached a higher Adult height (−1.4±0.6 vs. −1.9±.6 in pubertal children), the highest final height gain was achieved in those treated for at least 2years prepuberty (1.32±.5 SDS). Factors associated with greater adult height gain were: a) less height, weight and BMI at start of treatment, b) lower chronological and bone age with lower IGF-I before treatment, c) greater distance to target height, d) higher growth velocity the first and second year of treatment, and higher height gain before and during puberty. The percentage of patients with good response in the first year ranged from 46.6% to 81.6% depending on the criteria. Growth velocity increase ≥3cm/ first year correlated best with long-term response. CONCLUSION: rhGH treatment in children born SGA produced a varying increase in adult height that allowed them to reach their adult height. The best results occurred in the prepubertal group and did not depend on pituitary GH response


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/genética , Resultado do Tratamento , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento/administração & dosagem , Estudos Retrospectivos , Transtornos do Crescimento/etiologia , Índice de Massa Corporal , Peso-Estatura/genética
3.
Int J Mol Sci ; 21(2)2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31963456

RESUMO

Motor impairment is the most common and widely recognised clinical outcome after stroke. Current clinical practice in stroke rehabilitation focuses mainly on physical therapy, with no pharmacological intervention approved to facilitate functional recovery. Several studies have documented positive effects of growth hormone (GH) on cognitive function after stroke, but surprisingly, the effects on motor function remain unclear. In this study, photothrombotic occlusion targeting the motor and sensory cortex was induced in adult male mice. Two days post-stroke, mice were administered with recombinant human GH or saline, continuing for 28 days, followed by evaluation of motor function. Three days after initiation of the treatment, bromodeoxyuridine was administered for subsequent assessment of cell proliferation. Known neurorestorative processes within the peri-infarct area were evaluated by histological and biochemical analyses at 30 days post-stroke. This study demonstrated that GH treatment improves motor function after stroke by 50%-60%, as assessed using the cylinder and grid walk tests. Furthermore, the observed functional improvements occurred in parallel with a reduction in brain tissue loss, as well as increased cell proliferation, neurogenesis, increased synaptic plasticity and angiogenesis within the peri-infarct area. These findings provide new evidence about the potential therapeutic effects of GH in stroke recovery.


Assuntos
Infarto Encefálico/tratamento farmacológico , Modelos Animais de Doenças , Hormônio do Crescimento/administração & dosagem , Atividade Motora/efeitos dos fármacos , Recuperação de Função Fisiológica , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Cognição , Masculino , Camundongos , Camundongos Endogâmicos C57BL
4.
Arq. bras. med. vet. zootec. (Online) ; 72(1): 25-32, Jan.-Feb. 2020. tab, graf
Artigo em Português | LILACS, VETINDEX | ID: biblio-1088924

RESUMO

A fim de avaliar o efeito de diferentes doses da rbST sobre a dinâmica folicular, a produção e a maturação in vitro de oócitos, 20 vacas Sindi, divididas em três grupos, receberam um dispositivo de progesterona intravaginal, estradiol e PGF2α, além de 2mL de solução salina (grupo controle), 250 (grupo rbST 250) ou 500mg de rbST (grupo rbST 500). Cinco dias depois, realizou-se a ovum pick up, e os complexos cumulus-oócitos (CCOs) recuperados foram selecionados, classificados e maturados in vitro. Os dados de contagem foram comparados pelo procedimento glht (General Linear Hypothesis Test), e os dados em porcentagem foram submetidos ao qui-quadrado, no programa estatístico R, onde as diferenças foram consideradas significativas quando P<0,05. Não houve diferença (P>0,05) entre os grupos quanto à quantidade de folículos e à taxa de maturação. Os grupos rbST 250 e rbST 500 foram significativamente superiores (P<0,05) ao grupo controle em relação ao número de folículos grandes (0,42±0,20 vs. 0). O grupo rbST 500 apresentou maior (P<0,05) porcentagem de oócitos viáveis (91,52%) do que os grupos controle (67,85%) e rbST 250 (53,33%). A rbST aumenta o número de folículos grandes, e 500mg de rbST aumentam a porcentagem de oócitos viáveis em vacas Sindi.(AU)


In order to evaluate the effect of different doses of rbST on the follicular dynamics, production, and in vitro maturation of oocytes, 20 Sindhi cows were divided into three groups, receiving an intravaginal progesterone device, estradiol and PGF2α, and 2mL of solution saline (Control Group), 250 (rbST 250 Group) or 500mg rbST (rbST 500 Group). Five days later, the ovum pick up was performed, and the cumulus-oocyte (CCO) complexes recovered were selected, classified, and matured in vitro. The counting data were compared by the glht (General Linear Hypothesis Test) procedure, and the percentage data were submitted to Qui- square, in the statistical program R, where differences were considered significant when P< 0.05. There was no difference (P> 0.05) between the groups regarding follicle quantity and maturation rate. The rbST 250 and rbST 500 groups were significantly higher (P< 0.05) than the Control group in relation to the number of large follicles (0.42±0.20 versus 0). The rbST 500 group presented higher (P< 0.05) percentage of viable oocytes (91.52%) than the Control (67.85%) and rbST 250 (53.33%) groups. rbST increases the number of large follicles and 500mg rbST increases the percentage of viable oocytes in Sindhi cows.(AU)


Assuntos
Animais , Feminino , Bovinos , Oócitos , Indução da Ovulação/veterinária , Hormônio do Crescimento/administração & dosagem , Técnicas de Maturação in Vitro de Oócitos/veterinária
5.
Theriogenology ; 141: 180-185, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31550601

RESUMO

The aim of this research was to evaluate the effect of recombinant bovine somatotropin (bST) on pregnancy per artificial insemination (P/AI), cellular composition of the corpus luteum (CL) and endometrial gland morphometry. In Experiment 1, Nelore cows (n = 587) received a fixed-time artificial insemination (FTAI) protocol and, at insemination, received 0, 250 or 500 mg of bST subcutaneously (SC). In Experiment 2, Nelore cows (n = 243) received 0 or 500 mg of bST, SC, on D7 (D0 = day of FTAI). Blood samples were collected on D7 and D16 to measure progesterone (P4) concentrations. In Experiments 1 and 2, pregnancy diagnosis was performed 30 days after FTAI. In Experiment 3, Nelore heifers (n = 20) received a FTAI protocol, but were not inseminated, and on D0 (ovulation day), they received 0 (bST 0; n = 9) or 500 mg of bST (bST 500; n = 11), SC. The heifers were slaughtered on D15 (D0 = ovulation day), at which time the CL was evaluated for diameter, weight, a percentage of large (LLC) and small (SLC) luteal cells, and the concentration of progesterone in plasma measured. The number, perimeter and area of superficial and deep endometrial glands were evaluated. There was no difference in P/AI when bST was applied on D0 and D7. In Experiment 1, P/AI did not differ among treatments, with 59.28% (115/194), 58.38% (115/197) and 65.82% (129/196) for the bST 0, 250 and 500 treatments, respectively. In Experiment 2, P/AI did not differ between treatments, with 57.3% (71/124) and 60.5% (62/119) for the bST 0 and 500 treatments, respectively. Plasma progesterone concentrations on D16 was greater in the bST 500 (11.63 ±â€¯0.84 ng/mL) than bST 0 (9.83 ±â€¯0.88 ng/mL). In Experiment 3, there was no difference in ovarian diameter and weight, CL diameter, percentage of SLC, P4 concentrations and endometrial gland morphology. Heifers in the bST 500 treatment had heavier CL (3.11 ±â€¯0.32 vs. 2.25 ±â€¯0.20 g); however, the bST 0 treatment heifers had a greater percentage of LLC than did the bST 500 treatment (13.72 ±â€¯1.16% vs. 8.60 ±â€¯1.52). It was concluded that the doses of bST used in this study do not increase P/AI; however, they do cause changes in P4 concentration and the cellular composition of the CL.


Assuntos
Bovinos , Corpo Lúteo/citologia , Endométrio/anatomia & histologia , Hormônio do Crescimento/farmacologia , Inseminação Artificial/veterinária , Animais , Endométrio/fisiologia , Sincronização do Estro , Feminino , Hormônio do Crescimento/administração & dosagem , Gravidez , Proteínas Recombinantes
6.
Int. j. morphol ; 37(4): 1416-1421, Dec. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1040147

RESUMO

The indiscriminate use of anabolic steroids in gyms has been growing in a generalized way, among which, the most common is growth hormone (GH). In the short term GH may potentiate muscle growth, especially when taken in combination with resistance training. However, the effects of this hormone are not yet fully understood in the literature, especially in relation to collagen properties. The objective of this study was to evaluate the effect of the application of growth hormone (GH) and resistance training (RT) on the collagen properties of femoral bone tissue using Raman Spectroscopy. In this study 40 male rats were randomly distributed into four groups (n=10): control (C), control and GH application (GH), resistance training (T), and resistance training and GH application (GHT). The training consisted of four series of 10 water jumps, performed three times a week, with an overload corresponding to 50 % of body weight and duration of four weeks. GH was applied at a dosage of 0.2 IU/Kg (0.067 mg/kg) to each animal, three times a week, every other day. The animals were euthanized and the right femurs were collected for analysis of bone structure. Raman spectroscopy (RS) was used to observe the following compounds from their respective bands: type I collagen (662 cm-1), amide III (1243 cm-1), proteins including type I collagen (1278 cm-1), woven collagen (1322 cm-1), association of collagen, phospholipids, nucleic acid, and phosphate (1330 cm-1), and collagen and protein deformation (1448 cm-1). The results demonstrated an increase in the collagen properties in all analyzed variables, however, the T group presented a statistically significant difference (p<0.05). It is possible to conclude that isolated physical training was shown to be more efficient than when combined with the application of GH to increase the collagen properties of the femoral bone tissue.


El uso indiscriminado de anabolizantes en los gimnasios ha aumentado de forma generalizada, entre éstos la hormona de crecimiento (HC) es una de las más utilizadas, y a corto plazo puede potencializar el crecimiento muscular, principalmente cuando es realizado en combinación con el entrenamiento de fuerza. Sin embargo, los efectos de esta hormona aún no están totalmente esclarecidos en la literatura, especialmente en relación a las propiedades colágenas. El objetivo del estudio fue evaluar el efecto de la aplicación del HC y entrenamiento de fuerza (E) en las propiedades colágenas del tejido óseo femoral a partir de la utilización de la espectroscopía Raman. Se usaron 40 ratas Wistar distribuidos en cuatro grupos (n=10): control (C), control y aplicación del HC (HCC), entrenamiento de fuerza (E) y entrenamiento de fuerza y aplicación del HC (THC). El entrenamiento fue compuesto por cuatro series de 10 saltos acuáticos, realizados tres veces por semana, con sobrecarga correspondiente a 50 % del peso corporal y duración de cuatro semanas. El HC fue aplicado en una dosificación de 0,2 UI/Kg (0,067 mg/kg) en cada animal, tres veces por semana, en días no consecutivos. Los animales fueran eutanasiados y se retiró el fémur derecho para realización del análisis de la estructura ósea. La espectroscopía Raman (ER) fue utilizada para observar los siguientes compuestos a partir de las respectivas bandas: colágeno tipo I (662 cm-1), amida III (1243 cm1), proteínas, incluido colágeno tipo I (1278 cm-1), colágeno retorcido (1322 cm-1), asociación de colágeno, fosfolípidos, ácidos nucleicos y fosfato (1330 cm-1), deformación de colágeno y proteína (1448 cm-1). Hubo aumento en las propiedades colágenas en todas las variables analizadas, sin embargo, solamente el grupo E demostró una diferencia estadísticamente significativa (p<0,05). En conclusión, para el aumento de las propiedades colágenas del tejido óseo femoral, el entrenamiento físico aislado es más eficiente que el entrenamiento combinado con el uso de HC.


Assuntos
Animais , Masculino , Ratos , Resistência Física/fisiologia , Hormônio do Crescimento/farmacologia , Fêmur/efeitos dos fármacos , Fêmur/fisiologia , Hormônio do Crescimento/administração & dosagem , Exercício Físico/fisiologia , Colágeno/efeitos dos fármacos , Ratos Wistar , Microscopia/métodos
7.
ESC Heart Fail ; 6(6): 1216-1221, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31696666

RESUMO

AIMS: Although preliminary studies have demonstrated safety and effectiveness of single replacement therapy for growth hormone deficiency or testosterone deficiency in heart failure (HF), no data are available regarding the combined treatment with both GH and T in this setting. Thus, the aim of the present hypothesis generating pilot study was to evaluate the effectiveness and safety of multiple hormonal replacement therapies in chronic HF. METHODS AND RESULTS: Five stable HF with reduced ejection fraction patients, with a concomitant diagnosis of growth hormone deficiency and testosterone deficiency, on top of guideline-based HF treatment underwent 1 year of GH replacement therapy by subcutaneous injections of somatotropin at a dose of 0.012 mg/kg every second day. After 12 months, a T replacement treatment was added at a dosage of 1000 mg every 3 months. Each patient underwent a complete M-mode, two-dimensional, and Doppler echocardiographic examination, and an incremental symptom-limited cardiopulmonary exercise test on a bicycle ergometer at baseline (BL), after 1 year of GH treatment (V1), and after 1 year of combined GH + T treatments (V2). One-year of GH treatment resulted in a significant improvement in left ventricular ejection fraction (+5.4%, P < 0.01), New York Heart Association functional class (P < 0.05), and peak oxygen consumption (VO2 peak) (+19.3%, P < 0.01), and in a significant reduction in NT-proBNP levels (-35.1%, P < 0.01). Notably, one additional year of combined GH and T replacement therapy induced a further increase in VO2 peak (+27.7%, final delta change + 52.44%, P < 0.01), as well as a significant improvement in muscular strength, as assessed by handgrip dynamometry (+17.5%, final delta change + 25.8%, P < 0.01). These beneficial effects were paralleled with an improvement of the overall clinical status (as assessed by New York Heart Association class). Of note, neither adverse effects nor cardiovascular events were reported during the follow-up period. CONCLUSIONS: Our preliminary data suggest for the first time that combined replacement therapy with GH and T could be considered safe and therapeutic in HF patients with multiple hormone deficiencies, supporting the hypothesis that multiple hormone deficiencies syndrome can be considered as a novel and promising therapeutic target in HF. Further studies with a more robust design and larger population are needed.


Assuntos
Hormônio do Crescimento , Insuficiência Cardíaca/tratamento farmacológico , Terapia de Reposição Hormonal , Testosterona , Idoso , Hormônio do Crescimento/administração & dosagem , Hormônio do Crescimento/efeitos adversos , Hormônio do Crescimento/deficiência , Hormônio do Crescimento/uso terapêutico , Humanos , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Projetos Piloto , Volume Sistólico/fisiologia , Testosterona/administração & dosagem , Testosterona/efeitos adversos , Testosterona/deficiência , Testosterona/uso terapêutico
8.
Int J Mol Sci ; 20(17)2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31454882

RESUMO

The growth hormone is involved in skin homeostasis and wound healing. We hypothesize whether it is possible to improve pressure ulcer (PU) healing by locally applying the recombinant human growth hormone (rhGH) in a human skin mouse model. Non-obese diabetic/severe combined immunodeficient mice (n = 10) were engrafted with a full-thickness human skin graft. After 60 days with stable grafts, human skin underwent three cycles of ischemia-reperfusion with a compression device to create a PU. Mice were classified into two groups: rhGH treatment group (n = 5) and control group (n = 5). In the rhGH group for local intradermal injections, each had 0.15 mg (0.5IU) applied to the PU edges, once per week for four weeks. Evaluation of the wound healing was conducted with photographic and visual assessments, and histological analysis was performed after complete wound healing. The results showed a healing rate twice as fast in the rhGH group compared to the control group (1.25 ± 0.33 mm2/day versus 0.61 ± 0.27 mm2/day; p-value < 0.05), with a faster healing rate during the first 30 days. The rhGH group showed thicker skin (1953 ± 457 µm versus 1060 ± 208 µm; p-value < 0.05) in the repaired area, with a significant decrease in collagen type I/III ratio at wound closure (62 days, range 60-70). Local administration of the rhGH accelerates PU healing in our model. The rhGH may have a clinical use in pressure ulcer treatment.


Assuntos
Hormônio do Crescimento/uso terapêutico , Lesão por Pressão/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Biomarcadores , Biópsia , Colágeno/metabolismo , Modelos Animais de Doenças , Hormônio do Crescimento/administração & dosagem , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Camundongos , Lesão por Pressão/patologia , Proteínas Recombinantes , Pele/efeitos dos fármacos , Pele/patologia , Transplante de Pele
9.
J Dev Orig Health Dis ; 10(4): 459-468, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31347485

RESUMO

An adverse early life environment is associated with increased cardiovascular disease in offspring. Work in animal models has shown that maternal undernutrition (UN) during pregnancy leads to hypertension in adult offspring, with effects thought to be mediated in part via altered renal function. We have previously shown that growth hormone (GH) treatment of UN offspring during the pre-weaning period can prevent the later development of cardiometabolic disorders. However, the mechanistic basis for these observations is not well defined. The present study examined the impact of GH treatment on renal inflammatory markers in adult male offspring as a potential mediator of these reversal effects. Female Sprague-Dawley rats were fed either a chow diet fed ad libitum (CON) or at 50% of CON intake (UN) during pregnancy. All dams were fed the chow diet ad libitum during lactation. CON and UN pups received saline (CON-S/UN-S) or GH (2.5 µg/g/day; CON-GH/UN-GH) from postnatal day 3 until weaning (p21). Post-weaning males were fed a standard chow diet for the remainder of the study (150 days). Histological analysis was performed to examine renal morphological characteristics, and gene expression of inflammatory and vascular markers were assessed. There was evidence of renal hypotrophy and reduced nephron number in the UN-S group. Tumour necrosis factor-α, monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecular-1 and vascular cell adhesion molecule-1 gene expression was increased in UN-S offspring and normalized in the UN-GH group. These findings indicate that pre-weaning GH treatment has the potential to normalize some of the adverse renal and cardiovascular sequelae that arise as a consequence of poor maternal nutrition.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio do Crescimento/administração & dosagem , Hipertensão/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Inflamação/tratamento farmacológico , Rim/efeitos dos fármacos , Desnutrição/complicações , Animais , Feminino , Hipertensão/etiologia , Inflamação/etiologia , Inflamação/metabolismo , Rim/imunologia , Rim/patologia , Masculino , Gravidez , Ratos , Ratos Sprague-Dawley , Desmame
10.
Am J Med Genet A ; 179(9): 1826-1835, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31313492

RESUMO

Prader-Willi syndrome (PWS) is a genomic imprinting disorder characterized by infantile hypotonia with a poor suck and failure to thrive, hypogenitalism/hypogonadism, behavior and cognitive problems, hormone deficiencies, hyperphagia, and obesity. The Stanford Binet and Wechsler (WAIS-R; WISC-III) intelligence (IQ) tests were administered on 103 individuals with PWS from two separate cohorts [University of California, Irvine (UCI) (N = 56) and Vanderbilt University (N = 47)] and clinical information obtained including growth hormone (GH) treatment, PWS molecular classes, weight and height. Significantly higher IQ scores (p < .02) were found representing the vocabulary section of the Stanford Binet test in the growth hormone (GH) treated group when compared with non-GH treatment in the pediatric-based UCI PWS cohort with a trend for stabilization of vocabulary IQ scores with age in the GH treated maternal disomy (UPD) 15 subject group. Significant differences (p = .05) were also found in the adult-based Vanderbilt PWS cohort with 15q11-q13 deletion subjects having lower Verbal IQ scores compared with UPD 15. No difference in body mass index was identified based on the PWS molecular class or genetic subtype. Medical care and response to treatment with growth hormone may influence intelligence impacted by PWS genetic subtypes and possibly age, but more studies are needed.


Assuntos
Cromossomos Humanos Par 15/genética , Hormônio do Crescimento/administração & dosagem , Síndrome de Prader-Willi/tratamento farmacológico , Deleção de Sequência/genética , Adolescente , Adulto , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Humanos , Inteligência/efeitos dos fármacos , Testes de Inteligência , Masculino , Fenótipo , Síndrome de Prader-Willi/classificação , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/patologia , Teste de Stanford-Binet , Escalas de Wechsler , Adulto Jovem
11.
Drug Test Anal ; 11(11-12): 1698-1713, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31301268

RESUMO

The combination of growth hormone (GH) and recombinant erythropoietin (rEPO) is thought to be used particularly in endurance sports. Our objective was to reproduce a 2-week administration of rEPO microdoses alone or in combination with GH microdoses (three times a week) on healthy and athletic male subjects and to evaluate if GH had any additional effects compared to EPO treatment alone. The effects of the treatments on hematological parameters and VO2max were studied as well as the detection of GH in serum. While the rEPO microdose regimen was associated with a significant increase in reticulocytes, no clear elevation in hemoglobin concentration (HGB) was observed. Using a correction by plasma volume did not reveal more effects of EPO on HGB. Our results did not show any additional effect when the GH microdoses were co-administered. In addition, no clear increase in VO2max was observed after treatment, with an elevation in only half the subjects in both groups (EPO and EPO+GH). A clear effect of GH on insulin-like growth factor I (IGF-I) was seen but it was lower on procollagen III amino-terminal propeptide (P-III-NP). GH detection using the direct isoform test identified only one subject 24 hours after receiving GH. The GH biomarker test combining IGF-I and P-III-NP was not able to detect the GH administration. However, a longitudinal follow-up of the intraindividual variations showed a significant increase in IGF-I 24 and 48 hours after GH administration in most subjects, while the effect of GH microdoses on P-III-NP was less straightforward.


Assuntos
Eritropoetina/sangue , Eritropoetina/farmacologia , Hormônio do Crescimento/sangue , Hormônio do Crescimento/farmacologia , Doping nos Esportes , Relação Dose-Resposta a Droga , Contagem de Eritrócitos , Eritropoetina/administração & dosagem , Hormônio do Crescimento/administração & dosagem , Humanos , Masculino , Oxigênio/metabolismo , Reticulócitos/citologia , Reticulócitos/efeitos dos fármacos , Detecção do Abuso de Substâncias/métodos
12.
Transplantation ; 103(7): 1349-1359, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31241554

RESUMO

BACKGROUND: We evaluated the potential dysfunction caused by changes in growth hormone (GH) levels after brain death (BD), and the effects of modulating GH through exogenous epidermal growth factor (EGF) in steatotic and nonsteatotic grafts. METHODS: Steatotic and nonsteatotic grafts from non-BD and BD rat donors were cold stored for 6 hours and transplanted to live rats. Administration of GH and EGF and their underlying mechanisms were characterized in recipients of steatotic and nonsteatotic grafts from BD donors maintained normotensive during the 6 hours before donation. Circulating and hepatic GH and EGF levels, hepatic damage, and regeneration parameters were evaluated. Recipient survival was monitored for 14 days. Somatostatin, ghrelin, and GH-releasing hormones that regulate GH secretion from the anterior pituitary were determined. The survival signaling pathway phosphoinositide-3-kinase/protein kinase B that regulates inflammation (suppressors of cytokine signaling, high-mobility group protein B1, oxidative stress, and neutrophil accumulation) was evaluated. RESULTS: BD reduced circulating GH and increased GH levels only in steatotic livers. GH administration exacerbated adverse BD-associated effects in both types of graft. Exogenous EGF reduced GH in steatotic livers, thus activating cell proliferation and survival signaling pathways, ultimately reducing injury and inflammation. However, EGF increased GH in nonsteatotic grafts, which exacerbated damage. The benefits of EGF for steatotic grafts were associated with increased levels of somatostatin, a GH inhibitor, whereas the deleterious effect on nonsteatotic grafts was exerted through increased amounts of ghrelin, a GH stimulator. CONCLUSIONS: GH treatment is not appropriate in rat liver transplant from BD donors, whereas EGF (throughout GH inhibition) protects only in steatotic grafts.


Assuntos
Morte Encefálica/sangue , Fator de Crescimento Epidérmico/administração & dosagem , Fígado Gorduroso/metabolismo , Hormônio do Crescimento/administração & dosagem , Transplante de Fígado , Fígado/efeitos dos fármacos , Fígado/cirurgia , Animais , Morte Encefálica/patologia , Fator de Crescimento Epidérmico/sangue , Fator de Crescimento Epidérmico/toxicidade , Fígado Gorduroso/patologia , Hormônio do Crescimento/sangue , Hormônio do Crescimento/toxicidade , Fígado/metabolismo , Fígado/patologia , Masculino , Ratos Zucker , Fatores de Tempo
13.
Prensa méd. argent ; 105(5): 253-258, jun 2019. tab
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1024402

RESUMO

El presente trabajo realiza una investigación bibliográfica sobre el uso clínico de RhGH en pacientes adultos HIV en su rol inmunomodulador mediante búsqueda booleana en Pubmed de los términos RhGH yHIV en artículos de ensayos clínicos, únicamente en adultos a partir de los 19 o más años de edad hasta enero del 2019


Assuntos
Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Pesquisa/estatística & dados numéricos , Hormônio do Crescimento/administração & dosagem , Hormônio do Crescimento/imunologia , HIV/imunologia , Ensaio Clínico , Antirretrovirais/uso terapêutico , Sistema Imunitário/metabolismo
14.
Biomater Sci ; 7(7): 2934-2950, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31094367

RESUMO

Poor permeation across intestinal mucous barriers often limits the oral delivery of prospective therapeutic proteins and peptides (TPPs). In order to address this issue, cell penetrating peptide (CPP) together with PEG modified and pore-enlarged mesostructured silica nanoparticle (NP) were constructed to form the mucus-penetrating electrostatic particle-complexes, CPP/TPP/NP. Alone, CPP and TPP often present with poor stability, and their traditional electrostatic complex shows reduced pharmacodynamics. To provide satisfactory protection, silica NPs were loaded with CPP and TPP (CPP@NP and TPP@NP), respectively, and then CPP@NP and TPP@NP could together form CPP/TPP/NP via electrostatic interaction. As a result, CPP involvement with PEG modification showed an 8.45-, 1.62- and 5.09-fold increase in cellular uptake, exocytosis and final transcellular permeation in mucous conditions, respectively. It was found that CPP involvement mainly affected transport and exocytosis, and the PEG polymer significantly influenced mucous penetration and cellular uptake, which could further promote CPP ability for uptake and exocytosis. Additionally, NP-mediated CPP/TPP/NP showed a similar uptake mechanism with supporting carriers (clathrin-mediated endocytosis), and could strengthen transcellular routes (the endoplasmic reticulum-Golgi apparatus pathway and the lysosome route). Utilizing recombinant growth hormone (RGH) as a model TPP, oral administration of the RGH-loaded CPP/TPP/LMSN-PEG10k with hydrophilic and electroneutral properties induced 5.41- and 4.91-fold increases in pharmacodynamics in vitro and in vivo, respectively. Thus, CPP/TPP/NP significantly promoted mucous permeation and shows promising potential for oral delivery of TPPs.


Assuntos
Peptídeos Penetradores de Células/química , Portadores de Fármacos/química , Hormônio do Crescimento/administração & dosagem , Hormônio do Crescimento/química , Muco/metabolismo , Nanopartículas/química , Dióxido de Silício/química , Administração Oral , Transporte Biológico , Linhagem Celular Tumoral , Exocitose , Hormônio do Crescimento/metabolismo , Hormônio do Crescimento/uso terapêutico , Humanos , Interações Hidrofóbicas e Hidrofílicas , Permeabilidade , Polietilenoglicóis/química
15.
BMC Genomics ; 20(1): 336, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053056

RESUMO

BACKGROUND: Triploid coho salmon are excellent models for studying gene dosage and the effects of increased cell volume on gene expression. Triploids have an additional haploid genome in each cell and have fewer but larger cells than diploid coho salmon to accommodate the increased genome size. Studying gene expression in triploid coho salmon provides insight into how gene expression may have been affected after the salmonid-specific genome duplication which occurred some 90 MYA. Triploid coho salmon are sterile and consequently can live longer and grow larger than diploid congeners in many semelparous species (spawning only once) because they never reach maturity and post-spawning mortality is averted. Triploid fishes are also of interest to the commercial sector (larger fish are more valuable) and to fisheries management since sterile fish can potentially minimize negative impacts of escaped fish in the wild. RESULTS: The vast majority of genes in liver tissue had similar expression levels between diploid and triploid coho salmon, indicating that the same amount of mRNA transcripts were being produced per gene copy (positive gene dosage effects) within a larger volume cell. Several genes related to nutrition and compensatory growth were differentially expressed between diploid and triploid salmon, indicating that some loci are sensitive to cell size and/or DNA content per cell. To examine how robust expression between ploidies is under different conditions, a genetic/metabolic modifier in the form of different doses of a growth hormone transgene was used to assess gene expression under conditions that the genome has not naturally experienced or adapted to. While many (up to 1400) genes were differentially expressed between non-transgenic and transgenic fish, relatively few genes were differentially expressed between diploids and triploids with similar doses of the transgene. These observations indicate that the small effect of ploidy on gene expression is robust to large changes in physiological state. CONCLUSIONS: These findings are of interest from a gene regulatory perspective, but also valuable for understanding phenotypic effects in triploids, transgenics, and triploid transgenics that could affect their utility in culture conditions and their fitness and potential consequences of release into nature.


Assuntos
Animais Geneticamente Modificados/genética , Diploide , Regulação da Expressão Gênica , Hormônio do Crescimento/administração & dosagem , Fígado/metabolismo , Oncorhynchus kisutch/genética , Triploidia , Animais , Animais Geneticamente Modificados/crescimento & desenvolvimento , Animais Geneticamente Modificados/metabolismo , Hormônio do Crescimento/genética , Oncorhynchus kisutch/crescimento & desenvolvimento , Oncorhynchus kisutch/metabolismo , Transgenes
16.
Biomed Res Int ; 2019: 5939372, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31073528

RESUMO

Objective: This study aimed to examine the relationship between serum alanine aminotransferase (ALT) and growth hormone (GH) in children and adolescents with short stature. Methods: In this retrospective cohort study, 670 Chinese children and adolescents with short stature were included, and 253 of them received recombinant human GH (rhGH) therapy. Anthropometric and biochemical indicators were measured. GH peak levels were assessed after provocation tests with L-dopa and insulin. The subjects were divided into 3 groups according to the GH peak level. The association between the GH peak and ALT was analyzed. The change of ALT during rhGH therapy was assessed by a generalized additive mixed model. Results: Serum ALT and incidence of ALT elevation were both decreased across the GH tertiles (P = 0.002, 0.012, respectively). A univariate analysis showed that the GH peak was negatively associated with ALT (ß: -0.12; 95%CI: -0.22, -0.02; P = 0.023). Furthermore, multiple linear stepwise regression analysis demonstrated that the GH peak was independently related to ALT after adjusting for other confounding variables (ß: -0.12; 95%CI: -0.24, -0.00; P = 0.042). Besides, mean values of the change in ALT from baseline displayed that, during the early stages of rhGH treatment, serum ALT level indicated a temporary upward trend, but it subsequently gradually decreased (ß: -0.16; 95%CI: -0.23, -0.09; P < 0.001). Conclusions: GH secretion level was strongly negatively correlated with ALT in short children and adolescents. And rhGH therapy could reduce ALT level over time.


Assuntos
Alanina Transaminase/sangue , Nanismo/sangue , Hormônio do Crescimento/sangue , Proteínas Recombinantes/administração & dosagem , Adolescente , Antropometria , Estatura , Criança , China , Nanismo/tratamento farmacológico , Nanismo/fisiopatologia , Feminino , Hormônio do Crescimento/administração & dosagem , Hormônio do Crescimento/genética , Humanos , Insulina/sangue , Levodopa/sangue , Masculino , Proteínas Recombinantes/genética
17.
J Anim Sci ; 97(6): 2433-2440, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31066897

RESUMO

The goal of this project was to determine if increasing insulin-like growth factor-1 (IGF-1) concentrations in late pregnancy can stimulate mammogenesis in gilts. Yorkshire × Landrace gilts of a similar body weight (BW; 196.2 ± 6.2 kg) on day 89 of gestation were separated in 2 groups, namely, controls (CTL, n = 17) that were injected with sterile water, and porcine somatotropin-treated (pST, n = 20) that received injections of 5 mg of pST (Reporcin). Injections were given daily from days 90 to 109 of gestation and gilts were slaughtered on day 110 to collect mammary glands for compositional analyses. Blood samples were obtained on days 89, 96, 103, and 109 of gestation to measure IGF-1, free fatty acids (FFA), urea, glucose, and insulin concentrations. Treated gilts gained more BW (22.7 vs. 18.2 kg, P < 0.05) and lost more backfat (P < 0.05) than CTL gilts during the treatment period. There was a treatment × day effect (P < 0.01) on IGF-1, glucose, and urea concentrations. Concentrations of IGF-1 increased 4-fold (P < 0.01) in pST compared with CTL gilts on days 96, 103, and 109 of gestation. Insulin values were also greater on days 96 (P < 0.01) and 103 (P = 0.01), and tended to be greater (P < 0.10) on day 109 of gestation in pST gilts. Glucose was greater in pST than CTL gilts on days 96 (P < 0.01), 103 (P < 0.01), and 109 (P = 0.01). Concentrations of urea were lower (P < 0.01) on days 96, 103, and 109 of gestation in gilts receiving pST injections, and FFA was not altered by treatment on any sampling day (P > 0.10). Injections of pST did not affect mammary extraparenchymal tissue weight (P > 0.10) but increased mammary parenchymal mass (1922 vs. 1576 ± 124 g, P < 0.05). The composition of parenchymal tissue was also altered by treatment. Mammary parenchyma from pST gilts contained more (P < 0.05) protein, DNA and RNA and less fat (P < 0.05) and dry matter (P < 0.01) than that from CTL gilts. These findings provide a clear demonstration that increasing circulating IGF-1 in late-pregnant gilts can stimulate mammary development both in terms of total parenchymal mass and of parenchymal tissue composition.


Assuntos
Hormônio do Crescimento/farmacologia , Glândulas Mamárias Animais/efeitos dos fármacos , Suínos/fisiologia , Animais , Feminino , Hormônio do Crescimento/administração & dosagem , Gravidez , RNA/metabolismo
18.
Eur J Endocrinol ; 181(1): 79-91, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31100717

RESUMO

Objective: Growth hormone (GH) deficiency is related to increased cardiovascular mortality. We studied clinical status, concentration of amino-terminal-pro B-type natriuretic-peptide (NT-proBNP) and echocardiographic parameters during long-term GH replacement (GH-R). Methods: Fifty-one patients (29 females), 45.9 ± 11.3 years (mean ± s.d.), median follow-up 36.2 months, echocardiography and laboratory determinations initially and at 12-months intervals. Results: At the last follow-up (last observation carried forward) (LFU (LOCF)) insulin-like growth-factor-1 standard deviation score (IGF-1 SDS) was ±1 in 92% of the patients. The median NT-proBNP declined significantly and stabilized (-40.5%) at LFU (LOCF) due to patients with a basal NT-proBNP >125 ng/L (indicative of heart failure). The basal NT-proBNP and the final IGF-1 SDS were significant predictors of the NT-proBNP at LFU (LOCF). Initially left ventricular enddiastolic diameter (LVEDD), left ventricular posterior wall diameter (LVPWD) and ejection fraction (EF) were normal, while interventricular septum diameter (IVSD) and left ventricular mass index (LVMi) were slightly increased. LVPWD and IVSD had significantly declined by year three. The LVMi was moderately to severely abnormal in 37.3 and 52.0% of patients initially and at LFU (LOCF). At LFU (LOCF) LVMi and IGF-1 were significantly correlated in the 14 male patients of this subgroup. Conclusion: Long-term GH-R of GHD positively affected ISVD and LVPWD. In a subgroup of patients with severe GHD, LVMi increased concomitantly to the decline in NT-proBNP and this was positively correlated to the final IGF-1 concentration. Whether this observation indicates a positive development in a structurally altered heart muscle (reversal of adverse remodelling) or poses a future risk for heart failure needs further follow-up.


Assuntos
Hormônio do Crescimento/administração & dosagem , Insuficiência Cardíaca/etiologia , Terapia de Reposição Hormonal/métodos , Hormônio do Crescimento Humano/deficiência , Fatores de Tempo , Adulto , Esquema de Medicação , Ecocardiografia , Feminino , Seguimentos , Coração/efeitos dos fármacos , Humanos , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Resultado do Tratamento
19.
J Dairy Sci ; 102(7): 6679-6681, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31103299

RESUMO

Our previous published work demonstrated that feeding rumen-degradable valine to late-lactation dairy cows increased milk production compared with control-fed cows, with a response that was equivalent to that of recombinant bovine somatotropin. To further elucidate the response mechanism, we hypothesized that thyroxine (T4) and triiodothyronine (T3), which are important regulators of basal metabolism, may be involved. Previous short-term studies have demonstrated increased milk production when feeding iodinated casein. Eight multiparous Holstein dairy cows (255 ± 26.4 d in milk) were blocked by milk yield (34.1 ± 8.25 kg/d) and randomly assigned to 1 of 4 treatments using a replicated 4 × 4 Latin square design with 21-d periods (7 d for dietary adaptation and 14 d for data collection). Treatments were control (CON), a single injection of recombinant bovine somatotropin (rbST), and synthetic valine fed at 40 (V40) or 80 (V80) g/cow per day. Cows were fed a total mixed ration with a distillers dried grains carrier fed at 113.4 g/d containing no valine or added valine. Blood samples were collected twice during wk 2 and 3 of each period for T3 and T4 analysis. Concentrations of T4 (3.28, 3.90, 3.98, and 3.87 µg/dL for CON, rbST, V40, and V80, respectively) were increased for cows receiving rbST, V40, and V80 compared with CON cows. Concentrations of T3 (125.7, 140.7, 148.8, and 139.7 ng/dL) were increased for cows receiving rbST, V40, and V80 compared with CON cows, with cows receiving V40 having the highest T3 concentrations. In conclusion, feeding rumen-degradable valine increases plasma T4 and T3 concentrations, which would explain the mechanism leading to increased milk production.


Assuntos
Ração Animal , Bovinos/sangue , Dieta/veterinária , Tiroxina/sangue , Tri-Iodotironina/sangue , Valina/farmacologia , Animais , Feminino , Hormônio do Crescimento/administração & dosagem , Hormônio do Crescimento/metabolismo , Lactação/fisiologia , Leite , Distribuição Aleatória , Rúmen/metabolismo , Valina/administração & dosagem
20.
Fish Physiol Biochem ; 45(3): 1083-1090, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31093852

RESUMO

A comparison of the efficacy of salmon and bovine growth hormone to stimulate growth of coho salmon juveniles was performed. Oncorhynchus nerka (sockeye salmon) type II growth hormone (nGH2) was produced using a bacterial expression system, yielding approximately 25 mg of refolded recombinant protein per litre of cells. The purified nGH2 and bovine growth hormone (bGH) were tested in juvenile O. kisutch (coho salmon) over 24 weeks. Weekly intraperitoneal injections of 0.1 and 0.5 µg/g nGH2 resulted in a dose-dependent increase in weight and fork length compared to control fish injected with bovine serum albumin (BSA). Application of 0.5 µg/g bGH resulted in the same stimulation of growth as did 0.5 µg/g nGH2, indicating these proteins were equipotent. Following 6 weeks of treatment and a subsequent rest period of 7 weeks, coho salmon were further treated with bGH at 0.5 µg/g. A prior treatment with bGH did not reduce growth-promoting activity of bGH in subsequent treatments. Throughout the experiment, condition factor decreased at similar rates for all treatment groups. These data show that bGH, which is widely available, can be used to elevate growth rate in juvenile salmon comparably to homologous GH, and validate the use of bGH in physiological or ecological experiments where rapid growth is desired compared to that seen in wild type.


Assuntos
Hormônio do Crescimento/farmacologia , Oncorhynchus kisutch/crescimento & desenvolvimento , Animais , Relação Dose-Resposta a Droga , Hormônio do Crescimento/administração & dosagem , Distribuição Aleatória
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