Oś hormon wzrostu–insulinopodobny czynnik wzrostu a karcynogeneza

  The growth hormone (GH) and insulin-like growth factor (IGF) system plays an important role in the regulation of cell proliferation, differentiation, apoptosis, and angiogenesis. In terms of cell cycle regulation, the GH-IGF system induces signalling pathways for cell growth that compete with other signalling systems that result in cell death; thus the final effect of these opposed forces is critical for normal and abnormal cell growth. The association of the GH-IGF system with carcinogenesis has long been hypothesised, mainly based on in vitro studies and the use of a variety of animal models of human cancer, and also on epidemiological and clinical evidence in humans. While ample experimental evidence supports a role of the GH-IGF system in tumour promotion and progression, with several of its components being currently tested as central targets for cancer therapy, the strength of evidence from patients with acromegaly, GH deficiency, or treated with GH is much weaker. In this review, we will attempt to consolidate this data. (Endokrynol Pol 2016; 67 (4): 414–426)    Oś hormon wzrostu (GH)–insulinopodobny czynnik wzrostu (IGF) odgrywa istotną rolę w regulacji proliferacji i różnicowania komórek, apoptozy i angiogenezy. Oś GH–IGF wpływa na regulację cyklu komórkowego przez pobudzenie szlaku wzrostu komórki w stosunku do szlaków sygnałowych prowadzących do śmierci komórki, a ostateczny efekt oddziaływania tych dwóch sił ma podstawowe znaczenie dla prawidłowego lub nieprawidłowego wzrostu komórki. Hipotezy na temat powiązań osi GH–IGF z karcynogenezą pojawiły się wiele lat temu, głównie w oparciu o wyniki badań in vitro oraz badań z wykorzystaniem różnych zwierzęcych modeli raka występującego u ludzi. Chociaż liczne dane doświadczalne potwierdzają rolę osi GH–IGF sprzyjającą rozwojowi i progresji nowotworów, a nad kilkoma składowymi tej osi trwają obecnie badania oceniające ich przydatność jako główne cele terapii przeciwnowotworowej, to jednak siła dowodów uzyskanych u chorych z akromegalią, niedoborem GH lub osób leczonych GH jest znacznie słabsza. W niniejszej pracy przeglądowej spróbowano zebrać wszystkie te dane. (Endokrynol Pol 2016; 67 (4): 414–426)

Avaliação da eficácia e segurança do uso de hormônio de crescimento humano biossintético em crianças pré-puberes com insuficiência renal crônica e baixa estatura

Orientador: Luiz de Lacerda FilhoContem 29 folhas de anexoDissertação (mestrado) - Universidade Federal do Parana, Setor de Ciencias da SaudeResumo: Foram estudados os efeitos de 1 ano de tratamento com hormônio de crescimento humano biocinético (HCHB) sobre o crescimento linear, idade óssea, função renal e parâmetros metabólicos, em 10 crianças pre-puberes (5 meninas, idade media de 8,1 anos, variando de 5,9 a 11,5 anos; 5 meninos, idade media de 8,0 anos, variando de 3,8 a 12,2 anos) com baixa estatura e insuficiência renal crônica (IRC). Os critérios de inclusão foram: estatura abaixo do 2o desvio padrão negativo da media para a idade ou velocidade de crescimento abaixo do 25° percentil (TANNER, 1966); IRC diagnosticada no mínimo 12 meses antes do inicio do estudo e taxa de filtração glomerular < 50 ml/min/1,73 m² (calculada pela formula de Schwartz); níveis séricos normais de hormônios tireoideanos. O HCHB (GenotropinR) foi administrado na dose de 1.0 IU/kg/semana, em injeções diárias, via subcutanea. A media da velocidade de crescimento (VC) aumentou de 4,5 cm/ano para 8,6 cm/ano (p < 0,01); a media do escore do desvio padrão da VC (HV-SDS) passou de - 1,58 para 2,92 (p < 0,01); a media do escore do desvio padrao da estatura (H-SDS) passou de -3,30 para -2,8 (p < 0,01). O ganho médio de peso foi de 3,2 kg e a idade óssea avançou 1 ano neste período. Duas meninas iniciaram puberdade apos o 6o mes de tratamento. A taxa de filtração glomerular aumentou significativamente apos o 6o mes (p < 0,05) e retomou aos valores tratamento após um ano de uso da medicação. Houve aumento significativo dos níveis séricos de fosforo e insulina (p < 0 ,01), sendo que a glicemia e a frutosamina permaneceram normais. Outros parâmetros bioquímicos não mudaram significativamente. Não foram observados efeitos colaterais. Nossos resultados mostraram que o HCHB foi efetivo em melhorar o crescimento linear de crianças pre-puberes com IRC e baixa estatura.Abstract: The effects o f 1 year of recombinant DNA human growth hormone (rhGH) on growth rate, bone age, renal function and metabolic parameters were studied in 10 pre-pubertal short children (5 girls aged 5.9 to 11.5, mean o f 8.1; 5 boys aged 3.8 to 12.2, mean o f 8.0) with chronic renal failure. The inclusion criteria were: height below -2 SD or height velocity below the 25th centile (TANNER et al., 1966); chronic renal insufficiency diagnosed at least 12 months prior to entry into the study and glomerular filtration rate < 50 ml/min/1.73 m^ body surface area (estimated by Schwartz formula); and normal thyroid function. rHGH (GenotropinR), 1.0 IU/kg/week, was given daily by subcutaneous injections. The median height velocity (HV) increased from 4.5 cm/year to 8.6 cm/year (p < 0.01); the median HV-SDS changes were from -1.58 to 2.92 (p <0.01); H-SDS increased from -3.3 to -2.8 (p < 0 .01). Median weight gain during treatment was 3.2 kg and median bone age advanced 1 year. Two girls started puberty after 6 months of therapy. Glomerular filtration rate increased significantly (p < 0.05) at 6 months and returned to pre-treatment values at 1 year o f therapy. Serum phosphate and insulin increased significantly (p < 0.01) at 12 months; glucose and frutosamine remained normal. Other biochemical parameters did not change significantly. No side effects were observed. In conclusion rHGH was effective in improving the linear growth of pre-pubertal short children with chronic renal failure

The science behind the relations among cancer, height, growth patterns, and growth hormone axis

The association between growth hormone (GH) and carcinogenesis has long been postulated. The rationale for this association is that several components of the GH axis play an important role in the regulation of cell proliferation, differentiation, apoptosis, and angiogenesis and have been tested as targets for cancer therapy. Epidemiological and clinical studies have examined the association between height, growth patterns, and insulin-like growth factor 1 (IGF1) levels with the most common types of malignancies, while genome-wide association studies have revealed several height-associated genes linked to cancer and/or metastasis-driving pathways. In this context, a permissive role of the GH-IGF signaling system in the link between height and cancer risk has also been investigated. In animal and human models, genetic defects associated with GH deficiency or resistance are associated with protection from tumor development, while the risk of malignancies in acromegaly or in patients exposed to recombinant GH therapy has long been a matter of concern and scrutiny. In this review, we present a narrative and historical review covering the potential relations among height, growth patterns, GH axis, and cancer

Weaning and associated factors in children from low-income communities

Introduction: The average duration of breastfeeding is still insufficient and differ widely taking in account the location and specific characteristic of local people involved in these studies. Aim: This research aimed at studying factors associated to weaning among South Brazilian children living in a low-income household. Material and method: Cross-sectional study was carried out enrolling 124 mothers of 1 to 12-month-old children, who were interviewed at "Pastoral da Criança" (non-governmental organization) in Almirante Tamandaré, Paraná, Brazil. The risk of weaning considered was the dependent variable and the information collected from the questionnaires, independent variables. The method used to collect information in this study was Kaplan-Meier method and Cox regression model and Spearman's rank correlation (α = 0.05). Result: Actuarial life table presented a higher weaning conditional probability at 12 months of age, followed by first and fourth months of age. Multivariate analysis pointed out that contact with bottle feeding before the sixth month of age [HR=17.16 (2.34-125.86)] and contact with pacifier before the sixth months of age [HR=3.48 (1.90-6.38)] are risk factors associated with weaning. Among children who were not breastfed at the moment of the interview, breastfeeding duration presented a positive correlation with the ages when the children had their first contact with sugar (r s =+0.419, p=0.001) and negative correlation with the use of pacifier (r s =-0.300, p=0.017). Conclusion: Results from this study showed that the use of the feeding bottle and pacifier were related to a shorter breastfeeding time span at these communities

The influence of glycemic control on the oral health of children and adolescents with diabetes mellitus type 1

ABSTRACT Objective To evaluate the influence of disease control, expressed by the mean values of glycated hemoglobin (HbA1c), in the oral health of children and adolescents with diabetes mellitus type 1 (T1DM). Subjects and methods A cross sectional study involving 87 children and adolescents (59 girls), 10 ± 2.6 years old. The participants were divided into three groups: HbA1c ≤ 8%, 8% 10%. The duration of the disease, age and average HbA1c were obtained from their medical records. Oral health was evaluated according to the following indexes: Simplified Oral Hygiene Index (OHI-S); Community Periodontal Index (CPI); Decayed, Missing or Filled Teeth Index (DMFT/dmft) for permanent and deciduous teeth; and the stimulated salivary flow rate (SSFR). Results The median SSFR was 1.1 mL/min in the group with HbA1c ≤ 8%, 0.7 mL/min in the intermediary group and 0.6 mL/min in the HbA1c > 10% group. A significant decrease in salivary flow was observed with an increase in HbA1c (p = 0.007). The DMFT/dmft and CPI indexes were higher in individuals with higher HbA1c values. More caries-free individuals were found in the group with HbA1c ≤ 8% compared to those with HbA1c > 10%. The group with HbA1c > 10% exhibited more caries and bleeding gums than the other groups. HbA1c values in girls were higher than in boys. Conclusion Children and adolescents with unsatisfactory glycemic control, represented by higher HbA1c concentrations, exhibited a higher frequency of caries and gingivitis, and a reduction in salivary flow. Arch Endocrinol Metab. 2015;59(6):535-4

Use of physical activity and cardiorespiratory fitness in identifying cardiovascular risk factors in male brazilian adolescents

The aim of this study was to investigate the impact of physical activity (PA) and cardiorespiratory fitness (CRF) levels on the prevalence of overweight and high blood pressure levels in adolescents. In this observational, cross-sectional study, 614 boys aged 10-14 years were assessed for height, body mass, body mass index (BMI), waist circumference (WC) and blood pressure (BP). CRF was assessed using a run test (Léger Test) and subjects were then grouped according to their CRF level. PA level was assessed through a questionnaire (The Three Day Physical Activity Recall) and classified into two groups, namely > 300 minutes of PA/week and < 300 minutes of PA/week. Maturational stage was evaluated according to the development of pubic hair (self-assessment) as proposed by Tanner. We used statistical descriptive analysis, univariate and multivariate analyses in the total participants and subjects were divided by age. Fifty percent of the sample performed < 300 minutes of PA/week and 67.6% had unsatisfactory CRF levels. There was a higher prevalence of unsatisfactory CRF levels among subjects with altered BMI (overweight), WC (abdominal obesity) or BP (high blood pressure) for all age groups. PA history, however, did not show any significance. A total of 31% of participants were overweight, 24.8% had abdominal obesity and 15.4% had increased BP. Unsatisfactory CRF levels were found to be a better predictor for the diagnosis of cardiovascular diseases (CV) risk factors than PA history, regardless of age group