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ABSTRACT: The aim of this study was to investigate whether a secular trend in growth occurred during the last century in Pygmies from Cameroon (West Pygmies) and in Bantu rural farmers, the latter being studied to serve as controls.
The evolution in height of West Pygmies and Bantu farmers from 1911 to 2006 was evaluated using data from the literature as well as data gathered by our research team during an expedition to Cameroon in 2006.
During the last century, no secular trend in west Pygmies is apparent, as height changed from 151 cm to 155 cm in males and from 143 cm to 146 cm in females. A small though significant (p=0.026), increment (about 2 cm) was observed only in female subjects during the last ten years. By contrast, Bantu heights show a significant change from 1943 to 2006 for both males (from 159 cm to 172 cm; p=0.025) and females (from 148 cm to 160 cm; p=0.029).
Over the last century, the Bantu population exhibited a significant secular trend for height, whereas West Pygmies did not increase their linear growth. The lack of secular trend in Pygmies possibly suggests that their stature reflects adaptation to the forest lifestyle. We may hypothesize that not only environmental but epigenetic factors have also contributed to their growth potential.
Hormones (Athens, Greece) 04/2011; 10(2):144-8. · 2.44 Impact Factor
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Sara Pagani,
Eduardo A Chaler,
Cristina Meazza,
Mercedes Maceiras,
Maria Eugenia Gonzalez,
Marco A Rivarola,
Francesca Cantoni, Paola Travaglino,
Lucia Della Croce,
Kamilia Laarej,
Mauro Bozzola,
Alicia Belgorosky
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ABSTRACT: We analyzed the ability of the BaF3 cell line bioassay to select patients with biologically inactive GH. We first evaluated the biological response of the Ba/F3-hGHR cells to rhGH additional doses from 10 to 5000 pg/ml. The concentration points corresponding to the linear part of the curve were selected. We then analyzed a group of sera, diluted like the standard, including the entire range of GH concentrations that can be analyzed by bioassay. The serum/standard area below the curve ratio was calculated. Serum GH immunoactivity determined by IMMULITE/GH bioactivity ratios was calculated. Our experimental data showed that GH-bioactivity/GH-immunoactivity ratios below 0.303 are indicative of a bioinactive GH molecule. This bioassay would recognize only extreme cases of GH bioinactivity, and it would not be a useful tool in the search for patients with altered forms of GH.
Journal of pediatric endocrinology & metabolism: JPEM 08/2010; 23(8):783-8. · 0.88 Impact Factor
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ABSTRACT: The control of growth and nutritional status in the foetus and neonate is a complex mechanism, in which also hormones produced by adipose tissue, such as adiponectin and leptin are involved. The aim of this study was to evaluate levels of adiponectin, leptin and insulin in appropriate (AGA) and small for gestational age (SGA) children during the 1st year of life and to correlate these with auxological parameters.
In 33 AGA and 29 SGA infants, weight, length, head circumference, glucose, insulin, adiponectin and leptin levels were evaluated at the second day of life, and at one, six and twelve months, during which a portion of SGA could show catch-up growth (rapid growth in infants born small for their gestational age).
Both total and isoform adiponectin levels were comparable between AGA and SGA infants at birth and until age one year. These levels significantly increased from birth to the first month of life and then decreased to lower values at 1 year of age in all subjects. Circulating leptin concentrations were higher in AGA (2.1 +/- 4.1 ng/ml) than in SGA neonates (0.88 +/- 1.03 ng/ml, p < 0.05) at birth, then similar at the 1st and the 6th month of age, but they increased in SGA from six months to one year, when they showed catch-up growth. Circulating insulin levels were not statistically different in AGA and SGA neonates at any study time point. Insulin levels in both AGA and SGA infants increased over the study period, and were significantly lower at birth compared to one, six and 12 months of age.
During the first year of life, in both AGA and SGA infants a progressive decrease in adiponectin levels was observed, while a difference in leptin values was correlated with the nutritional status.
Italian Journal of Pediatrics 03/2010; 36:26.
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ABSTRACT: Several reports suggest a role of growth hormone (GH) in the regulation of the haematopoietic system, as regards the normal differentiation and function of blood cells. The aim of this study was to evaluate the influence of rhGH therapy on erythropoietin (Epo) and granulocyte-colony stimulating factor (G-CSF) levels in 18 prepubertal short children with idiopathic GH deficiency (GHD) (n = 8) or without GHD (n = 10), during the first year of treatment. In non-GHD children Epo levels significantly decreased and G-CSF levels increased from basal to 12 months of therapy, whereas in GHD children they did not change significantly. Circulating levels of G-CSF are significantly lower in GHD than in non-GHD children. In non-GHD children the number of red blood cells, haemoglobin and haematocrit values significantly increased after 1 year of rhGH treatment. rhGH therapy influences Epo and G-CSF levels in short non-GHD children, while it shows no effects in GHD children.
Journal of pediatric endocrinology & metabolism: JPEM 09/2009; 22(9):837-43. · 0.88 Impact Factor
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Mauro Bozzola, Paola Travaglino,
Nicola Marziliano,
Cristina Meazza,
Sara Pagani,
Maurizia Grasso,
Maithè Tauber,
Marta Diegoli,
Andrea Pilotto,
Eliana Disabella,
Paolo Tarantino,
Agnese Brega,
Eloisa Arbustini
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ABSTRACT: The stature is a highly heritable trait controlled by genetic and environmental factors. The African Pygmies represent a paradigmatic example of non-disease-related idiopathic short stature (ISS), showing a similar endocrine profile of Caucasian individuals with ISS. Pygmy children show normal anthropometric and endocrine parameters until puberty, while adult Pygmies show normal baseline and post-stimulation serum growth hormone (GH) levels but low values of baseline serum GH-binding protein (GHBP) and insulin-like growth factor-I (IGF-I). This discrepancy suggests a defective response to GH occurring in adulthood since Pygmies lack both the pubertal serum IGF-I surge and the growth spurt. However, sequencing of the key genes of the GH-IGF-I axis failed to identify Pygmy specific variants or haplotypes. We therefore aimed at assessing whether the quantitative gene expression profile of two key genes of the GH-IGF-I axis, GH and GHR, was also similar in low-stature and normal stature populations. We showed that the GH gene expression is 1.8-fold reduced and the GH receptor (GHR) gene expression is 8-fold reduced in adult Pygmies in comparison with sympatric adult Bantu, and that this reduction is not associated with sequence variants of the GHR gene. The marked decrease of the GHR expression in Pygmies is associated with reduced serum levels of the IGF-I and GHBP. Our results, documenting a markedly reduced GHR gene expression in adult Pygmies, could contribute to elucidate the mechanisms involved in ISS in Caucasoid subjects.
Molecular Genetics and Metabolism 06/2009; 98(3):310-3. · 3.19 Impact Factor
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ABSTRACT: The relationship among circulating values of growth hormone (GH), thymulin, and zinc in 19 healthy human neonates at birth and at the 4th month of age, and in their respective mothers, was investigated. Cytofluorimetric analysis on some CD antigen markers was conducted on cord blood and peripheral blood mononuclear cells. Active thymulin and zinc plasma levels increased in newborns in comparison with their mothers. In neonates serum GH levels increased with a significant decline later. The expression of CD molecules from newborns at birth and from infants at the 4th month of age was inversely correlated with active thymulin, zinc, and GH levels, whereas CD4 antigen marker was positively correlated with the same parameters at the 4th month of life. A novel interrelationship among active thymulin, zinc, and GH exists from the early up to the late phase of newborn life, in which maternal zinc, via lactation, may be involved.
American Journal of Perinatology 05/2007; 24(4):227-33. · 1.32 Impact Factor
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Paola Travaglino,
Fabio Buzi,
Cristina Meazza,
Sara Pagani,
Carmine Tinelli,
Lorenzo Iughetti,
Vincenzo De Sanctis,
Gianluca Aimaretti,
Dimitri Poddighe,
Salvatore Barberi,
Mauro Bozzola
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ABSTRACT: The aim of the present study was to investigate whether short children with normal growth hormone (GH) immunoreactivity, but reduced bioactivity (bioinactive GH) could benefit from rhGH treatment as GH deficient (GHD) patients.
We evaluated 12 pre-pubertal children (8 M, 4 F), with GH deficiency-like phenotype showing normal serum GH peak levels (>10 ng/ml), measured by immunofluorimetric assay (IFMA-GH), in contrast with a reduced GH bioactivity (bio-GH), evaluated using the Nb(2) cells. We also evaluated 15 age-matched GHD pre-pubertal children (11 M, 4 F) with serum GH peak <5 ng/ml. Both groups were treated with rhGH therapy at the dose of 0.23 mg/kg/week s.c.
Serum bio-GH/IFMA-GH ratio at peak time for each patient during the provocative test was significantly lower in bioinactive GH than in GHD children (0.29 vs. 2.05, p = 0.00001). Recombinant human GH therapy induced a significant (p < 0.001) increase in growth rate in both groups during the first 2 years. In the third year of treatment, while growth rate in GHD children is maintained, in bioinactive GH patients it decreases remaining, however higher compared to the pre-treatment one.
Short rhGH therapy given to selected bioinactive GH children improve growth rate and might result in greater final adult height.
Hormone Research 01/2006; 66(4):189-94. · 2.48 Impact Factor
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ABSTRACT: The aim of the present study was to investigate the effect of exogenously administered human GH (hGH) on serum levels of interleukin (IL)-4, IL-6, IL-12 and tumour necrosis factor (TNF)-alpha in GH-deficient (GHD) children.
We evaluated 13 short prepubertal GHD children, aged between 2 and 13 years, and 13 age-matched healthy subjects as controls. Circulating cytokine values were evaluated in basal conditions in all children, and 6 and 24 h following the 1st hGH injection (0.23 mg/kg per week), and then after 3 months of hGH treatment in GHD patients. Serum levels of IL-4, IL-6, IL-12 and TNF-alpha were measured by commercially available ELISAs.
No significant differences were found between controls and GHD children in basal values of serum IL-4, IL-6, IL-12 and TNF-alpha (P > 0.05 by Mann-Whitney U test). Analysis of cytokine levels during hGH treatment showed significant changes over time in TNF-alpha and IL-6 levels (P = 0.0014 and P = 0.00 024 respectively), with the more pronounced effect observed at 6 h following the first administration of hGH (i.e. increase in IL-6 (Wilcoxon matched pairs test, P = 0.0015) and TNF-alpha levels (P = 0.0015)). No significant changes over time were observed in IL-4 and IL-12 serum levels.
In vivo release of the pro-inflammatory cytokines IL-6 and TNF-alpha can be affected by hGH treatment in GHD children, suggesting a direct effect of GH on the immune function.
European Journal of Endocrinology 03/2005; 152(2):207-10. · 3.42 Impact Factor
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ABSTRACT: A growing body of evidence indicates a bi-directional relationship between the neuroendocrine system and immune functions. It is well known that lymphoid organs such the thymus, the spleen and peripheral blood produce growth hormone (GH) and GH receptor is expressed on different subpopulations of lymphocytes. Many in vitro and in animal studies demonstrate an important role of GH in immunoregulation. GH stimulates T and B cells proliferation and immunoglobulin synthesis, enhances the maturation of myeloid progenitor cells and is also able to modulate cytokine response. However, in humans GH deficiency (GHD) is not usually associated with immunodeficiency and only minor abnormalities of immune function have been reported, as compared to those observed in GHD animals. It is possible that in humans the GH produced locally in the immune system compensates for the lack of endocrine GH. In this review the main actions of GH on the immune system in vitro, in animal models and in humans are summarized.
Pediatric endocrinology reviews: PER 09/2004; 1 Suppl 3:490-5.
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ABSTRACT: The aim of the present study was to investigate the effect of exogenously administered GH on serum levels of interleukin (IL)-1beta, IL-2, IL-12, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma and their relation with IGF-I levels in normal short stature children.
23 short prepubertal non GH-deficient children (10 females and 13 males) whose mean+/-s.d. chronological age was 11.95+/-1.85 Years (from 8.80 to 14.89 Years), and mean+/-s.d. bone age was 10.48+/-2.44 Years, were evaluated during a somatomedin generation test (human GH 0.1 IU/kg per day for 4 days) to exclude a partial GH resistance as the cause of short stature; 34 sex- and age-matched healthy subjects were studied as controls. Circulating cytokine values were measured in basal conditions in all children, and 12 h following the 4th GH subcutaneous injection in the 23 short children only.
No significant differences were found between short children and controls in basal values of serum IGF-I (192.1+/-18.3 and 198.2+/-28.2 ng/ml respectively). In short subjects there was a significant increase in serum IGF-I levels after the 4th GH injection (from 192.1+/-18.3 ng/ml, i.e. -1.16+/-0.16 standard deviation score (SDS) to 338.2+/-27.1 ng/ml, i.e. 0.14+/-0.17; P<0.00001). No significant differences were found between short children and controls in basal concentrations of serum INF-gamma (19+/-4 and 26+/-5 mIU/ml respectively), IL-1alpha (24.950+/-3.613 and 20.896+/-2.778 pg/ml respectively), IL-2 (3.945+/-1.209 and 4.794+/-0.562 pg/ml respectively), IL-12 (1.093+/-0.269 and 1.976+/-0.596 pg/ml respectively), and TNF-alpha (1.794+/-0.559 and 2.188+/-0.346 pg/ml respectively). Likewise, a significant increase was found in serum INF-gamma (before 19+/-4 and after four GH injections 185+/-57 mIU/ml respectively; P<0.008), IL-1beta (24.950+/-3.613 to 43.339+/-5.431 pg/ml respectively; P<0.0001), IL-2 (3.945+/-1.209 to 9.165+/-2.331 pg/ml respectively; P<0.003), IL-12 (1.093+/-0.269 to 3.724+/-0.637 pg/ml respectively; P<0.0007) and TNF-alpha (1.794+/-0.559 to 9.266+/-3.066 pg/ml respectively; P<0.01).
Cytokine release can be affected by short-term GH administration in normal children indicating a direct influence of GH on the immune system.
European Journal of Endocrinology 11/2003; 149(5):397-401. · 3.42 Impact Factor
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ABSTRACT: To evaluate serum and synovial fluid (SF) levels of macrophage migration inhibitory factor (MIF) and in vitro MIF production by peripheral blood mononuclear cells (PBMCs) in patients with juvenile idiopathic arthritis (JIA).
Serum, SF, and culture supernatant levels of MIF were measured by enzyme-linked immunosorbent assay. Production of MIF by PBMCs was investigated by culturing PBMCs in the absence or presence of 2 different concentrations of concanavalin A.
Serum MIF levels were increased in patients with JIA, and the highest levels were present in patients with systemic-onset JIA. In systemic-onset JIA, serum levels of MIF correlated with the persistence of systemic features and the number of active joints. PBMCs from patients with systemic-onset JIA, when cultured under unstimulated conditions or at suboptimal stimulation, released higher amounts of MIF compared with those from patients with oligoarticular-onset JIA or healthy controls. MIF levels in the SF of patients with systemic-onset JIA were significantly higher than those in patients with oligoarticular-onset JIA. In individual joints, in both systemic-onset JIA and oligoarticular-onset JIA, SF MIF levels were inversely correlated with the duration of the clinical remission induced by intraarticular administration of triamcinolone hexacetonide.
MIF appears to be a relevant cytokine in the pathogenesis of JIA, particularly in systemic-onset JIA.
Arthritis & Rheumatism 02/2002; 46(1):232-7. · 7.87 Impact Factor
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ABSTRACT: The aim of the present study was to establish whether growth hormone (GH) treatment in vivo affects pro-inflammatory cytokine production by resting or in vitro, activated, cultured, peripheral blood mononuclear cells (PBMC) from children with complete growth hormone deficiency (GHD). We evaluated 11, pre-pubertal children (6 males and 5 females) with GHD, aged between 6 and 14 years, and 9, age- and sex-matched healthy subjects were studied as controls (CTRLs). Freshly isolated PBMC were cultured for 4 or 24 h in X-VIVO medium in the presence or absence of 0.01 microg/mL lipopolysaccharide for the determination of TNF-alpha and IL-6 production; alternatively, cells were incubated 24 h in X-VIVO medium with or without 25 microg/mL Concanavalin A for IFN-gamma production. Cytokines were measured in the cell supernatants by enzyme-linked immunosorbent assay kits. The results of the present study provide evidence that spontaneous and/or mitogen-induced, in vitro PBMC production of pro-inflammatory cytokines is lower in GHD children than in healthy, age-matched individuals (p<0.05 by the Mann-Whitney U-test). After 3 months of GH therapy, cytokine production was significantly (p<0.05 by the Wilcoxon test) increased, but was still lower than in healthy controls. It is reasonable to speculate that severe GH deficiency can cause alterations in the pro-inflammatory cytokine-induced immune response in humans, and that GH treatment can ameliorate this important immunological function.
European cytokine network 16(1):65-9. · 1.73 Impact Factor
