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1.
Wiad Lek ; 73(1): 63-67, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32124808

RESUMO

OBJECTIVE: The aim: To study the dynamics of markers of angiogenesis based on insulin-like growth factor-1 (IGF-1) and endostatin, as well as to determine 6-month survival in patients taking zofenopril from the first day of AMI with and without obesity. PATIENTS AND METHODS: Materials and methods: using enzyme immunoassay, we determined the level of endostatin and IGF-1 in serum on days 1 and 12 in patients with AMI with the presence and absence of obesity, and a statistical processing of the data obtained. RESULTS: Results: The relationship between obesity and angiogenesis indicators, both activators and inhibitors, was determined, and a significant relationship was found between zofenopril therapy and angiogenesis activator IGF-1. Differences in the survival of patients with complicated AMI were determined depending on the choice of ACE inhibitor in favor of a higher survival rate of patients who took zofenopril. CONCLUSION: Conclusions: patients who underwent complicated AMI, taking zofenopril, have a higher survival rate during the 6-month follow-up period. Zofenopril stimulated angiogenesis in the examined patients, which was expressed in patients with and without obesity.


Assuntos
Captopril/análogos & derivados , Endostatinas/uso terapêutico , Fator de Crescimento Insulin-Like I/uso terapêutico , Infarto do Miocárdio , Obesidade/tratamento farmacológico , Captopril/uso terapêutico , Humanos , Infarto do Miocárdio/tratamento farmacológico
2.
Chem Biol Interact ; 317: 108960, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31981573

RESUMO

Tripartite motif (TRIM) protein family is a group of proteins, which belongs to RING family of ubiquitin E3 ligases. TRIM proteins are involved in oncogenesis, while the roles in different cancers are controversial. However, the expression pattern and biological functions of TRIM47 in breast cancer remain unclear. In the present study, we aimed to investigate the function of TRIM47 in the progression and metastasis of breast cancer. TRIM47 was found to be significantly up-regulated in breast cancer tissues and cell lines. TRIM47 knockdown in breast cancer cell lines significantly inhibited cell proliferation, migration, and invasion. Besides, TRIM47 knockdown regulated the expressions of the epithelial-mesenchymal transition (EMT)-related markers including increase in E-cadherin, and decrease in N-cadherin, vimentin and Snail. Xenograft tumor assay proved that TRIM47 knockdown also suppressed tumor growth in vivo. Furthermore, TRIM47 knockdown markedly inhibited the activation of PI3K/Akt signaling pathway, while the effects of TRIM47 knockdown were reversed by the treatment of insulin-like growth factor-1 (IGF-1), which is an activator of PI3K/Akt. Taken together, the findings indicated that knockdown of TRIM47 suppressed tumorigenesis and progression of breast cancer through the inhibition of PI3K/Akt pathway, and suggested that TRIM47 might be a potential therapy target for breast cancer treatment.


Assuntos
Neoplasias da Mama/metabolismo , Carcinogênese/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Carcinogênese/efeitos dos fármacos , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Transformação Celular Neoplásica , Progressão da Doença , Transição Epitelial-Mesenquimal/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Humanos , Fator de Crescimento Insulin-Like I/farmacologia , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos
3.
Int J Occup Environ Med ; 11(1): 15-23, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31905192

RESUMO

BACKGROUND: Birth weight is very important for long-term physical, mental, health, and brain development. Pesticide exposure is thought to interfere with fetal growth, among others, through disruption of the function of the insulin-like growth hormone-1 (IGF-1) hormone. OBJECTIVE: To analyze the relationship between exposure to pesticides during pregnancy and low-birth weight (LBW) through the disruption of the IGF-1 hormone. METHODS: In a case-control study, babies born with LBW (birth weight <2500 g) and those born later with normal birth weight (=2500 g) at 2 hospitals in Brebes were chosen as cases and controls, respectively. Maternal pesticide exposure was measured by interview using a questionnaire. Umbilical serum IGF-I level was tested using the ELISA method. RESULTS: There was a significant relationship between pesticide exposure during pregnancy and LBW (OR 6.8; 95% CI 2.0 to 22.9) and low umbilical serum IGF-1 levels (OR 3.6; 95% CI 1.2 to 11.1). There was a significant relationship between low umbilical serum IGF-1 levels and LBW (OR 8.9; 95% CI 2.4 to 32.1). CONCLUSION: There was a significant relationship between pesticide exposure during pregnancy and LBW through the umbilical serum IGF-1 reduction pathway.


Assuntos
Sangue Fetal/química , Recém-Nascido de Baixo Peso/fisiologia , Fator de Crescimento Insulin-Like I/análise , Exposição Materna/efeitos adversos , Organofosfatos/toxicidade , Praguicidas/toxicidade , Peso ao Nascer , Estudos de Casos e Controles , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Indonésia , Recém-Nascido , Gravidez
4.
Eur J Endocrinol ; 182(3): 363-374, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31961798

RESUMO

Objective: Pregnancy-associated plasma protein-A2 (PAPP-A2) is a metalloproteinase that cleaves IGFBP-3 and IGFBP-5. Human mutations in PAPPA2 result in short stature with a low percentage of free IGF-I. Little is known about PAPP-A2 levels and the regulation of free IGF-I throughout childhood. We examined PAPP-A2 and intact IGFBP-3 levels in childhood and explored associations between PAPP-A2, free and total IGF-I, and total and intact IGFBP-3 and their relationship to the percentage of free to total IGF-I and anthropometric factors. Design: Cross-sectional study at a single center. Methods: PAPP-A2, free IGF-I, and intact IGFBP-3 levels were measured in childhood (3-18 years old) and an evaluation of the relationship between these proteins and anthropometric factors. Results: In 838 children, PAPP-A2 consistently decreased throughout childhood. In contrast, free IGF-I increased. A pubertal peak in free IGF-I was present in females but was less evident in males. Intact and total IGFBP-3 increased throughout childhood; however, intact IGFBP-3 had a more marked rise than total IGFBP-3. Percent free IGF-I decreased with no distinct pubertal peak. PAPP-A2 levels positively correlated with the percent free IGF-I (Male, Female; r = 0.18, 0.38; P < 0.001) and negatively with intact IGFBP-3 (Male, Female; r = -0.58, -0.65; P < 0.0001). Conclusions: This is the first study to describe serum PAPP-A2 and intact IGFBP-3 in children between 3 and 18 years of age. Our correlative findings suggest that PAPP-A2 is an important regulator of the percent free IGF-I which can be a marker of perturbations in the GH/IGF-I axis.


Assuntos
Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Proteína Plasmática A Associada à Gravidez/metabolismo , Adolescente , Desenvolvimento do Adolescente , Antropometria , Estatura , Peso Corporal , Criança , Desenvolvimento Infantil , Pré-Escolar , Feminino , Humanos , Masculino , Puberdade/metabolismo , Valores de Referência
5.
Eur J Endocrinol ; 182(3): 375-383, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31972545

RESUMO

Context: Cardiovascular disease is one of the main causes of morbidity in active acromegaly due to the increased prevalence of risk factors and arterial consequences of increased growth hormone levels. No in vivo study has evaluated the consequences of acromegaly on the retinal microvasculature. Objective: The aim of this study was to identify in vivo the presence of morphological alterations of retinal arterioles in subjects with acromegaly. Patients and methods: Single-center retrospective study of a cohort of 60 subjects with acromegaly, matched to 60 controls, who were referred for adaptive optics camera (AOC) from September 2014 to December 2016. Of the subjects with acromegaly, 19 had an active disease (AD) and 41 a controlled disease (CD) based on the IGF1 ratio (IGF1r). Retinal arteriolar remodeling was previously assessed using adaptive optics camera (AOC) in order to measure wall-to-lumen ratio (WLR), wall thickness (WT), internal diameter (ID) and wall cross sectional area (WCSA). Results: WLR was significantly higher in AD subjects compared to CD subjects and controls (AD: 0.311 ± 0.06, CD: 0.279 ± 0.04, controls: 0.281 ± 0.04, P = 0.031). A significant positive correlation was observed between WLR and IGF-1r (R2 = 0.215, P < 0.001), even after adjustment for gender, age, systolic blood pressure (SBP) and the presence of dopamine agonist treatment (R2 = 0.406, P < 0.001). Retinal arteriolar anatomical indices were comparable between CD and controls. Conclusion: Active acromegaly is associated with the presence of small retinal arteriolar remodeling. These results provide new perspectives to better stratify cardiovascular risk and consequently optimize treatment in acromegaly.


Assuntos
Acromegalia/diagnóstico por imagem , Arteríolas/diagnóstico por imagem , Fator de Crescimento Insulin-Like I/metabolismo , Artéria Retiniana/diagnóstico por imagem , Remodelação Vascular , Acromegalia/tratamento farmacológico , Acromegalia/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Óptica , Tamanho do Órgão , Artéria Retiniana/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença
6.
Eur J Endocrinol ; 182(3): 285-292, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31917681

RESUMO

Objective: To examine all-cause mortality rates in patients with acromegaly on pegvisomant and identify pertinent risk factors, including insulin-like growth factor I (IGF-I). Design: Retrospective cohort analysis of data from ACROSTUDY (global surveillance study of patients with acromegaly treated with pegvisomant). Methods: Kaplan-Meier analyses and Cox regression techniques were used to examine survival rates. Standardized mortality ratios (SMR) with reference to general population (WHO GBD 2016) were estimated. Multiplicative multiple Poisson regression models were used to characterize the association between SMR, IGF-I, and other risk factors associated with mortality risk. Results: The study consisted of 2077 subjects who were followed for a median interval of 4.1 years, contributing to 8957 patient-years. Higher on-treatment IGF-I (P = 0.0035), older attained age (P < 0.0001), and longer duration of acromegaly (>10 years) before starting pegvisomant (P = 0.05) were associated with higher mortality rates. In reference to general population rates, higher SMR (1.10, 1.42, and 2.62, at attained age 55 years) were observed with higher serum IGF-I category (SMR trend: 1.44 (44%)/per fold level of IGF-I/ULN (95% CI: 1.10, 1.87), P = 0.0075). SMR increased per year of younger attained age (1.04 (1.02-1.04), P < 0.0001) and were higher for longer disease duration (>10 years) before starting pegvisomant (1.57 (1.02, 2.43), P = 0.042). Serum IGF-I levels within the normal range during pegvisomant therapy were associated with all-cause mortality rates that were indistinguishable from the general population. Conclusions: Higher on-treatment IGF-I, older attained age, and longer duration of acromegaly before starting pegvisomant are associated with higher all-cause mortality rates. Younger patients with uncontrolled acromegaly have higher excess all-cause mortality rates in comparison with older patients.


Assuntos
Acromegalia/tratamento farmacológico , Hormônio do Crescimento Humano/análogos & derivados , Mortalidade , Receptores da Somatotropina/antagonistas & inibidores , Acromegalia/metabolismo , Adulto , Fatores Etários , Idoso , Causas de Morte , Estudos de Coortes , Feminino , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Tempo para o Tratamento
7.
Eur J Endocrinol ; 182(3): 275-284, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31917680

RESUMO

Background: If biochemical control of acromegaly is not achieved by operation and medication, radiotherapy may be indicated. Objective: To describe fractionated radiotherapy (FRT) and stereotactic radiosurgery (SRS) regarding excess of IGF-1 and pituitary function. Design and methods: A retrospective analysis of 352 patients (4126 patient-years) from the German Acromegaly Registry was performed. Follow-up was 1.0-45.1 years after radiotherapy. Therapeutic success was defined by low or normal IGF-1 according to center-specific reference ranges without (= remission) or on (= controlled disease) suppressive medication. Results: Time between radiotherapy and last follow-up was 13.0 ± 8.2 years for FRT (n = 233) and 8.9 ± 5.0 years for SRS (n = 119, P < 0.001). Median (IQR) basal growth hormone before radiotherapy was 6.3 (2.9-16.2) ng/mL for FRT and 3.5 (1.8-6.9) ng/mL for SRS (P < 0.001). Mean time in uncontrolled state was 3.0 years after FRT and 2.1 years after SRS (95% CI for the difference is 0.1 to 1.6 years, P = 0.021). The 10-year calculated remission rate was 48% for FRT and 52% for SRS (95% CI for the difference is -18 to 26% age points, P = 0.74) and the respective controlled disease rate was 23 and 26%. The odds ratio for adrenocorticotropic or thyreotropic insufficiency was 0.54 (95% CI: 0.30-1.00, P = 0.049) in SRS compared to FRT patients. Conclusion: Both after FRT and SRS about 75% of patients with acromegaly are in remission or controlled after 10 years. A slightly faster achievement of target values was observed after SRS. The rate of pituitary insufficiency in FRT patients is significantly higher.


Assuntos
Acromegalia/radioterapia , Acromegalia/cirurgia , Adenoma/radioterapia , Adenoma/cirurgia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/radioterapia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Radiocirurgia/métodos , Adulto , Estudos de Coortes , Terapia Combinada , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Alemanha , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
8.
Eur J Endocrinol ; 182(3): 319-331, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31958318

RESUMO

Objective: Acromegaly has a negative influence on health-related quality of life (HRQoL). Previous studies provide limited information on the course of HRQoL during treatment. This study aims to assess the effect of treatment on the course of HRQoL at six predefined time points. Design: This prospective study examines HRQoL in treatment-naive patients before and during the first 2.5 years of acromegaly treatment. Methods: Therapy-naive acromegaly patients completed three validated questionnaires (RAND-36, AcroQoL, and the Appearance Self-Esteem (ASE)) at six predetermined time points before, during, and after treatment. Outcomes were correlated to IGF1 levels and disease control status. Results: Twenty-seven acromegaly patients completed the questionnaires at all time points. After treatment, all patients had controlled acromegaly. Scores of RAND-36 domains General health, Vitality and Health change, and all AcroQoL dimensions (except for Relations) improved during treatment (P ≤ 0.003); the largest changes were detected during the first year. Gender influenced HRQoL scores, since AcroQoL scores significantly improved in males but not in females. Over time, IGF1 levels were negatively correlated with HRQoL. After 2.5 years of follow-up, HRQoL of controlled patients was still lower than in the general population. Conclusion: HRQoL of acromegaly patients was considerably reduced at diagnosis. Disease control was associated with an improvement of HRQoL scores. Males showed a more pronounced improvement than females. The largest changes were detected in the first year of treatment. However, HRQoL during and after treatment remained impaired in acromegaly patients, emphasizing the need of additional support.


Assuntos
Acromegalia/psicologia , Acromegalia/terapia , Qualidade de Vida/psicologia , Adulto , Idoso , Feminino , Nível de Saúde , Hormônios/deficiência , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/psicologia , Estudos Prospectivos , Autoimagem , Fatores Sexuais , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
10.
J Clin Endocrinol Metab ; 105(3)2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31650157

RESUMO

CONTEXT: The X-linked immunoglobulin superfamily, member 1 (IGSF1), gene is highly expressed in the hypothalamus and in pituitary cells of the POU1F1 lineage. Human loss-of-function mutations in IGSF1 cause central hypothyroidism, hypoprolactinemia, and macroorchidism. Additionally, most affected adults exhibit higher than average IGF-1 levels and anecdotal reports describe acromegaloid features in older subjects. However, somatotrope function has not yet been formally evaluated in this condition. OBJECTIVE: We aimed to evaluate the role of IGSF1 in human and murine somatotrope function. PATIENTS, DESIGN, AND SETTING: We evaluated 21 adult males harboring hemizygous IGSF1 loss-of-function mutations for features of GH excess, in an academic clinical setting. MAIN OUTCOME MEASURES: We compared biochemical and tissue markers of GH excess in patients and controls, including 24-hour GH profile studies in 7 patients. Parallel studies were undertaken in male Igsf1-deficient mice and wild-type littermates. RESULTS: IGSF1-deficient adult male patients demonstrated acromegaloid facial features with increased head circumference as well as increased finger soft-tissue thickness. Median serum IGF-1 concentrations were elevated, and 24-hour GH profile studies confirmed 2- to 3-fold increased median basal, pulsatile, and total GH secretion. Male Igsf1-deficient mice also demonstrated features of GH excess with increased lean mass, organ size, and skeletal dimensions and elevated mean circulating IGF-1 and pituitary GH levels. CONCLUSIONS: We demonstrate somatotrope neurosecretory hyperfunction in IGSF1-deficient humans and mice. These observations define a hitherto uncharacterized role for IGSF1 in somatotropes and indicate that patients with IGSF1 mutations should be evaluated for long-term consequences of increased GH exposure.


Assuntos
Imunoglobulinas/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Proteínas de Membrana/fisiologia , Neurossecreção/fisiologia , Somatotrofos/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Hormônio do Crescimento/biossíntese , Humanos , Imunoglobulinas/deficiência , Fator de Crescimento Insulin-Like I/análise , Peptídeos e Proteínas de Sinalização Intercelular/deficiência , Masculino , Proteínas de Membrana/deficiência , Camundongos , Pessoa de Meia-Idade
11.
Toxicol Lett ; 321: 44-53, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31811911

RESUMO

This study was aimed to investigate the effect of prenatal ethanol exposure (PEE) on the susceptibility of offspring rats to glomerulosclerosis and to explore the mechanism. Pregnant Wistar rats were intragastrically administered ethanol (4g/kg·d) from gestational day (GD) 9 to GD 20, and the control group was given equal volume of normal saline. The offspring rats were all fed with high-fat diet after weaning, and were sacrificed at postnatal week 24 (PW24). The results revealed that the adult offspring kidneys in the male and female PEE groups exhibited higher glomerulosclerosis index and interstitial fibrosis index compared with the high-fat diet control groups, accompanied by elevated serum creatinine level. The protein expression of Nephrin and WT1, which were the marker genes of podocytes, was significantly decreased, whereas the protein expression of desmin and α-SMA, the marker genes of mesenchymal cells, was remarked enhanced in the male and female PEE groups. Compared with the high-fat diet control groups, the mRNA and protein expressions of renal angiotensin II receptor type 2 (AT2R) were decreased in the male PEE group, but increased in the female PEE group. PEE increased the mRNA and protein expressions of glucocorticoid (GC) activation system and inhibited the expression of insulin-like growth factor 1 (IGF1) signaling pathway in male offspring kidney; on the contrary, in female offspring kidney, PEE inhibited the mRNA and protein expression of glucocorticoid activation system and increased the expression of IGF1 signaling pathway. Taken together, PEE increased the susceptibility of the adult offspring to glomerulosclerosis, and the programming of renal AT2R or GC-IGF1 is respectively involved in the toxicity of PEE to the male or female offspring.


Assuntos
Dieta Hiperlipídica , Etanol/toxicidade , Glomerulonefrite/etiologia , Glomérulos Renais/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Transdução de Sinais/efeitos dos fármacos , Animais , Feminino , Fibrose , Regulação da Expressão Gênica , Idade Gestacional , Glomerulonefrite/genética , Glomerulonefrite/metabolismo , Glomerulonefrite/patologia , Glucocorticoides/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Masculino , Gravidez , Ratos Wistar , Receptor Tipo 2 de Angiotensina/genética , Receptor Tipo 2 de Angiotensina/metabolismo , Transdução de Sinais/genética
12.
Int J Radiat Biol ; 96(1): 112-128, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30475652

RESUMO

Purpose: Göttingen minipig (G-MP) displays classic gastrointestinal acute radiation syndrome (GI-ARS) following total body irradiation (TBI) at GI doses which are lethal by 10-14 days. In collaboration with BARDA, we are developing a hemi-body/partial body irradiation (PBI) model by exposing only the abdomen and lower extremities to study GI structure/function impairment, natural history of injury and recovery, as well as correlative biomarkers out to 30 days.Materials and methods: Twenty-four G-MP were exposed to either 12 or 16 Gy (LINAC Elekta); head, forelimbs, and thorax were outside the irradiation field, sparing ∼50% of the bone marrow. Animals were followed for 30 days with euthanasia scheduled at pre-set intervals to study the time course of GI injury and recovery. Hematological profiles, clinical symptoms, gross- and histo-pathology including markers of proliferation and apoptosis in the small intestines, gut function parameters (food tolerance, digestion, absorption, citrulline production), and levels of two biomarkers, CRP and IGF-1, were evaluated.Results: PBI at 16 Gy yielded higher lethality than 12 Gy. Unlike TBI, PBI did not cause severe pancytopenia or external hemorrhage, as expected, and allowed to focus the injury on GI organs while sparing the radiation sensitive heart and lung. Compromised animals showed inactivity, anorexia, vomiting, diarrhea, and weight loss. Histology revealed that in 12 Gy irradiated animals, lesions recovered overtime. In 16 Gy irradiated animals, lesions were more pronounced and persistent. BrdU and Ki67 labelling demonstrated dose-dependent loss of crypts and subsequent mucosal ulceration which recovered over time. Minimal apoptosis was observed at both doses. Reductions in food tolerance, digestion, absorption, and citrulline production were time and dose-dependent. Loss of citrulline reached a nadir between 6-12 days and then recovered partially. CRP and IGF-1 were upregulated following PBI at GI doses.Conclusions: This lower hemi-body irradiation model allowed for extended survival at GI-specific ARS doses and development of a well-controlled GI syndrome with minimal hematopoietic injury or confounding mortality from cardiopulmonary damage. A dose-dependent impairment in the intestinal structure resulted in overall decreased gut functionality followed by a partial recovery. However, while the structure appeared to be recovered, not all functionality was attained. PBI induced systemic inflammation and altered the IGF-1 hormone indicating that these can be used as biomarkers in the minipig even under partial body conditions. This PBI model aligns with other minipig models under BARDA's large animal consortium to test medical countermeasure efficacy against a less complex GI-specific ARS injury.


Assuntos
Síndrome Aguda da Radiação/patologia , Síndrome Aguda da Radiação/fisiopatologia , Trato Gastrointestinal/fisiopatologia , Trato Gastrointestinal/efeitos da radiação , Síndrome Aguda da Radiação/sangue , Animais , Contagem de Células Sanguíneas , Proteína C-Reativa/metabolismo , Citrulina/sangue , Digestão/efeitos da radiação , Modelos Animais de Doenças , Relação Dose-Resposta à Radiação , Trato Gastrointestinal/patologia , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Suínos , Porco Miniatura , Fatores de Tempo
13.
Ecotoxicol Environ Saf ; 188: 109876, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31704319

RESUMO

This study aimed to assess the levels of pyrethroids and organochlorine residues in the tissues of cultured Mugil capito and in water samples obtained from three different sites (Al-Hamol, Al-Riad and Sidi Salem; referred to as Area 1, Area 2, and Area 3, respectively) in the Delta region, Egypt. The study also assessed the biochemical markers in exposed mullet and evaluated the impact of these residues on the expression of insulin-like growth factor 1 (IGF-1) in muscle and cytochrome P4501A (CYP1A) in liver tissues using qRT-PCR and SDS-PAGE methods. The results revealed that pesticide residue levels in the water were variable, but were lower than detected levels in fish. Significant (P < 0.05) differences were found across the three study areas in terms of serum ALT, but the serum AST level was not significantly (P > 0.05) elevated in all study regions. Serum creatinine and urea levels were significantly (P < 0.05) elevated in area 3. Furthermore, glutathione and malondialdehyde concentrations significantly increased (P < 0.05) in liver tissues in area 3. Using the qRT-PCR technique, the results revealed that the expression level of IGF-1 was most significant in area 3, while the expression level of CYP1A was most significant in area 1. The protein profile showed some differences in band numbers and molecular weights of protein bands across different regions. Overall, the alteration in biochemical parameters revealed pesticide interference with the metabolic processes of fish. Furthermore, the pesticide pollution had an effect on the expression of IGF-1 and CYP1A genes and led to changes in the protein profile. Therefore, these markers can be used to monitor fish distress following exposure to the pollutant.


Assuntos
Família 1 do Citocromo P450/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Hidrocarbonetos Clorados/toxicidade , Fator de Crescimento Insulin-Like I/genética , Proteínas Musculares/metabolismo , Piretrinas/toxicidade , Smegmamorpha/metabolismo , Animais , Aquicultura , Egito , Biomarcadores Ambientais/genética , Hidrocarbonetos Clorados/análise , Hidrocarbonetos Clorados/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Proteínas Musculares/química , Resíduos de Praguicidas/análise , Resíduos de Praguicidas/metabolismo , Resíduos de Praguicidas/toxicidade , Piretrinas/análise , Piretrinas/metabolismo , Alimentos Marinhos/análise , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/metabolismo
14.
Eur J Endocrinol ; 182(3): 255-264, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31863690

RESUMO

Background/objective: Data on metabolic impairments in Cushing's syndrome and GH deficiency all suggest that the relationship between cortisol and GH/IGF-I axis in obesity may have a role in the related diseases. However, studies focusing only on one of these hormones are often controversial in paediatrics. We aimed to explore the simultaneous relationship between cortisol and IGF-I with the metabolic alterations in paediatric obesity. Subjects/methods: Retrospective cross-sectional study in a tertiary care center. We recruited 876 (441 males and 435 females) overweight and obese children and adolescents. A complete clinical and biochemical evaluation including OGTT was performed. Cortisol and IGF-I SDS were divided in quartiles and then crossed to explore the reciprocal influence of high/high, low/low, and high/low levels of each one on the metabolic alterations of obesity. Results: Subjects in the higher quartiles of IGF-I-SDS and cortisol had an increased risk of hypertension, hypercholesterolemia, high levels of triglycerides, and reduced HDL cholesterol. Diversely, lower IGF-I-SDS quartiles were associated with higher blood glucose, insulin, insulin resistance, and reduced insulin sensitivity levels with the rise of cortisol quartiles. Conclusions: We observed that apart from glucose metabolism that is associated with low IGF-I and high cortisol levels, the other parameters known to be associated with increased cardiovascular risk were related to high levels of both IGF-I and cortisol, even if within normal range. Cortisol and IGF-I play a complex role in the comorbidities of obesity, and the evaluation of both variables could clarify some of the discordant results.


Assuntos
Hidrocortisona/sangue , Fator de Crescimento Insulin-Like I/análise , Obesidade/metabolismo , Sobrepeso/metabolismo , Adolescente , Glicemia/metabolismo , Criança , Colesterol/sangue , Estudos Transversais , Feminino , Teste de Tolerância a Glucose , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/epidemiologia , Hipertensão/sangue , Hipertensão/epidemiologia , Resistência à Insulina , Masculino , Estudos Retrospectivos , Risco , Triglicerídeos/sangue
15.
Theriogenology ; 141: 173-179, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31550600

RESUMO

To investigate the association of health status and parity with hormone profiles during the transition period and reproductive parameters in Holstein dairy cows, a prospective observational cohort study was carried out including only healthy primiparous (PP, n = 116) and multiparous (MP, n = 172) cows at the beginning of the study. A subset of 120 healthy and sick cows was randomly selected for insulin, IGF-I, leptin and adiponectin determination. Primiparous cows had greater IGF-I and adiponectin concentrations (P < 0.05) and tended (P=0.07) to have greater insulin concentrations than MP cows. While healthy and sick MP and sick PP cows presented a sharp decrease in IGF-I concentrations after calving, healthy PP cows maintained them. Postpartum adiponectin concentrations were lower in sick than in healthy MP cows. A greater percentage of healthy cows ovulated during the first 7 weeks after calving when compared to sick cows (67.9% vs 50%, P=0.002) and a similar trend was found for MP vs PP cows (64% vs 53%, P=0.01). More healthy cows were inseminated in comparison to sick cows (94% vs 76.5%, P < 0.01) and more PP than MP cows (90.4% vs 82.7%, P < 0.05). Similarly, healthy cows presented a greater proportion of pregnancy than sick cows (75% vs 54%, P < 0.01) and the proportion of pregnancy was higher in PP than in MP cows (74% vs 56%, P=0.04). Health status interacting with parity yielded different endocrine profiles, which may partially explain the differences in reproductive performance.


Assuntos
Adiponectina/sangue , Doenças dos Bovinos/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Insulina/sangue , Leptina/sangue , Paridade , Animais , Bovinos , Doenças dos Bovinos/sangue , Feminino , Fertilidade , Lactação , Gravidez
16.
J Physiol Anthropol ; 38(1): 16, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31806017

RESUMO

BACKGROUND: Epidemiological data regarding the association between serum levels of IGF-I and bone mineral acquisition during childhood are scarce. Here, we investigated the association between serum levels of IGF-I and bone status during puberty. METHODS: We analyzed prospective 3-year follow-up data of 254 community-dwelling children who completed both baselines (at age 11.2 years) and follow-up (at age 14.2 years) surveys in Hamamatsu, Japan. Total body (TB) bone area and bone mineral parameters were assessed using dual-energy X-ray absorptiometry. RESULTS: During the 3-year follow-up period, there were significant (P < 0.05) increases in total body less head (TBLH) areal bone mineral density (aBMD), TBLH bone mineral content (BMC), and TB bone area, and a significant decrease in TB bone mineral apparent density (BMAD, volumetric bone mineral density, vBMD). IGF-I levels showed significant positive relationships with TBLH BMC and TBLH aBMD at both baseline and follow-up. TBLH aBMD in boys and TB BMAD in girls at follow-up showed significant increases from the lowest to highest quartiles of baseline IGF-I levels after adjusting for confounding factors. Similarly, changes in TBLH aBMD in boys and TB BMAD in girls during the 3-year follow-up period showed significant increases from the lowest to highest quartiles of baseline IGF-I levels after adjusting for confounding factors. CONCLUSIONS: These results suggest that pubertal children with high levels of serum IGF-I tended to have high bone mineral acquisition later on.


Assuntos
Densidade Óssea/fisiologia , Desenvolvimento Ósseo/fisiologia , Fator de Crescimento Insulin-Like I/análise , Adolescente , Criança , Feminino , Seguimentos , Humanos , Japão , Masculino
17.
BMC Infect Dis ; 19(1): 1020, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791247

RESUMO

BACKGROUND: Vitamin D deficiency, determined by blood levels of 25-hydroxyvitamin D [25(OH) D, i.e. the major vitamin D form in blood], has been shown to associate with all-cause mortalities. We recently demonstrated that blood levels of 1,25-dihydroxyvitamin D [1,25(OH)2D, i.e. the active vitamin D] were significantly lower in non-survivors compared to survivors among sepsis patients. Unexpectedly, despite the well documented roles of 1,25(OH)2D in multiple biological functions such as regulation of immune responses, stimulation of antimicrobials, and maintenance of barrier function, 1,25(OH)2D supplementation failed to improve disease outcomes. These previous findings suggest that, in addition to 1,25(OH)2D deficiency, disorders leading to the 1,25(OH)2D deficiency also contribute to mortality among sepsis patients. Therefore, this study investigated the mechanisms leading to sepsis-associated 1,25(OH)2D deficiency. METHODS: We studied mechanisms known to regulate kidney 25-hydroxylvitamin D 1α-hydroxylase which physiologically catalyzes the conversion of 25(OH) D into 1,25(OH)2D. Such mechanisms included parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), fibroblast growth factor 23 (FGF-23), and kidney function. RESULTS: We demonstrated in both human subjects and mice that sepsis-associated 1,25(OH)2D deficiency could not be overcome by increased production of PTH which stimulates 1α-hydroxylase. Further studies showed that this failure of PTH to maintain blood 1,25(OH)2D levels was associated with decreased blood levels of IGF-1, increased blood levels of FGF-23, and kidney failure. Since the increase in blood levels of FGF-23 is known to associate with kidney failure, we further investigated the mechanisms leading to sepsis-induced decrease in blood levels of IGF-1. Our data showed that blood levels of growth hormone, which stimulates IGF-1 production in liver, were increased but could not overcome the IGF-1 deficiency. Additionally, we found that the inability of growth hormone to restore the IGF-1 deficiency was associated with suppressed expression and signaling of growth hormone receptor in liver. CONCLUSIONS: Because FGF-23 and IGF-1 have multiple biological functions besides their role in regulating kidney 1α-hydroxylase, our data suggest that FGF-23 and IGF-1 are warranted for further investigation as potential agents for the correction of 1,25(OH)2D deficiency and for the improvement of survival among sepsis patients.


Assuntos
Sepse/sangue , Sepse/complicações , Deficiência de Vitamina D/etiologia , Vitamina D/análogos & derivados , Animais , Estudos de Casos e Controles , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Fator de Crescimento Insulin-Like I , Rim/efeitos dos fármacos , Testes de Função Renal , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hormônio Paratireóideo/sangue , Sepse/fisiopatologia , Transdução de Sinais , Vitamina D/sangue , Vitamina D/metabolismo , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/fisiopatologia
18.
Orv Hetil ; 160(45): 1774-1783, 2019 Nov.
Artigo em Húngaro | MEDLINE | ID: mdl-31680542

RESUMO

The existence of insulin-like growth factors (IGFs) was recognized in connection with the stimulation of sulfate incorporation into cartilage. IGFs take part in the embryonal development and postnatal growth, in interaction with the growth hormone (GH). The physiological effects of IGF1 are promotion of tissue growth and development, stimulation of cell proliferation, effects on lipid and carbohydrate metabolism, anti-aging, anti-inflammatory, anabolic, anti-oxidant, neuro- and hepatoprotective properties. Our knowledge about the GH/IGF axis is diverse, partly contradictory, their research is continued intensively nowadays. We considered it worthwhile to review and interpret this information. Study on GH/IGF medical reports, with particular reference to the less known metabolic control. 75% of the growth factors are produced in the liver by GH and insulin stimulation; their effects are expressed on specific receptors, and modified by specific binding proteins. IGF1 directly increases the muscle mass, bone density, and the structure of the bones. Intestinal microbiota induces secretion of IGF1, which promotes the development and remodeling of the bones. Short-chain fatty acids, produced in microbial fermented fibers, induce secretion of IGF1, suggesting that microbial activity also affects bone health via IGF1. IGF1 also has a direct and indirect glucose-lowering effect, enhances free fatty acid oxidation in the muscle, reducing the flow of free fatty acid into the liver, improving insulin signaling, resulting in the reduction of hepatic glucose output, and improves insulin sensitivity. IGF1 directly influences the expression of circadian BMAL1 in hypothalamic cells: this refers to the newly recognized 'zeitgeber' role of IGF1. The bioactivity of insulin-like peptides in the brain is characterized by neuronal survival, excitatory and inhibitory neurotransmission, maintenance of normal free fatty acid levels, improvement of cognitive function, protection against cell damage, neurogenesis and angiogenesis. The effects of IGF2 are less outlined, however, it has a relevant role in the development of the fetus, and acts protectively on the brain. Lack or over-expression of IGF1 can be detected or may causally associated in many pathological conditions. According to these collected data, insulin sensitivity may be improved by different pathways. The role of IGFs in these processes should be a task of future research. Orv Hetil. 2019; 160(45): 1774-1783.


Assuntos
Hormônio do Crescimento/fisiologia , Fator de Crescimento Insulin-Like I/fisiologia , Humanos , Insulina , Fígado , Transdução de Sinais
19.
Biochemistry (Mosc) ; 84(10): 1213-1219, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31694517

RESUMO

Diabetes mellitus is characterized by increased platelet activation which is determined by many factors including changes in the expression of membrane proteins. The aim of this study was to investigate the sensitivity of human platelets to the insulin-like growth factor (IGF) system in patients with poorly controlled type 2 diabetes mellitus (DM2). Ligand binding was analyzed using 125I-labelled IGF-1 and insulin, and relative expression of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) was evaluated by Western blotting. Platelet aggregation in the presence of IGF-1 was studied by the plate aggregometry assay. We found that platelets from DM2 patients exhibited significantly higher IGF-1 binding and upregulation of IGF-1R expression in comparison with healthy individuals. Both insulin binding and IR expression were lower in the DM2 group, but the differences with the healthy control were statistically insignificant. The potentiating effect of IGF-1 on the thrombin-induced activation of platelets was detected in both groups but was significantly more pronounced in the DM2 patients. The initial rate of platelet activation in the presence of IGF-1 positively correlated with the concentration of glycated hemoglobin. Platelets isolated from DM2 patients displayed elevated expression of the IGF-1R subunits, which might have contributed to the higher sensitivity of these cells to IGF-1 in thrombin-initiated aggregation by increasing the rate of platelet activation. However, further experiments are needed to investigate the role of IGF-1 in thrombotic complications that usually accompany diabetes.


Assuntos
Plaquetas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Fator de Crescimento Insulin-Like I/isolamento & purificação , Masculino , Pessoa de Meia-Idade
20.
Medicine (Baltimore) ; 98(44): e17680, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689787

RESUMO

Hepatocellular carcinoma (HCC) is a lethal disease worldwide. In this study, we sought to explore the expression of insulin-like growth factor-1 receptor (IGF-1R) and its prognostic value in HCC.The expressions of IGF-1R mRNA and protein were estimated using quantitative real-time polymerase chain reaction and immunohistochemistry assays, respectively. The association between IGF-1R expression and clinicopathologic characteristic of patients with HCC was analyzed through Chi-squared test. Kaplan-Meier analysis and multivariate Cox analysis were performed to analyze prognostic value of IGF-1R in HCC.The IGF-1R was significantly upregulated in HCC tissues at both mRNA and protein levels compared with adjacent normal ones (P < .01). Its expression was associated with tumor node metastasis stage (P = .037) and lymph node metastasis (P = .027) of patients with HCC. Patients with HCC with high expression of IGF-1R had worse overall survival than those with low expression. IGF-1R might be a potential prognostic biomarker for HCC (hazard ratio [HR] = 1.912, 95% confidence interval [CI]: 1.023-3.572, P = .042).The IGF-1R expression level is upregulated in HCC tissues and may act as a prognostic biomarker for the disease.


Assuntos
Carcinoma Hepatocelular/patologia , Fator de Crescimento Insulin-Like I/biossíntese , Neoplasias Hepáticas/patologia , Idoso , Biomarcadores Tumorais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima
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