AGA
N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase precursor (EC 3.5.1.26) (Aspartylglucosaminidase) (Glycosylasparaginase) (N4-(N-acetyl-beta-glucosaminyl)-L-asparagine amidase) [Contains: Glycosylasparaginase alpha chain; Glycosylasparaginase beta chain]
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Cellular senescence, a phenomenon of irreversible growth arrest of mammalian cells, is involved in various age-related phenomena in organisms. Hair follicle dermal papilla (DP) cells play important roles in the regulation of hair growth and loss. We examined the implication of cellular senescence of DP cells in androgenetic alopecia (AGA), the most common form of male hair loss, and searched for the compounds that have a beneficial effect on the prevention of AGA. Expression of the 5α-reductase type II (SRD5A2) gene, which plays a key role in the development of AGA, was examined by quantitative RT-PCR and Western blotting analysis in DP cells. Besides, DP cells were cultured with the extracts of herbs used in traditional Ayurvedic medicine to search for the compounds that have a beneficial effect on the growth of DP cells. We found that expression of the SRD5A2 was up-regulated in senescent DP cells. We also found that the herbal extract of Plumbago zeylanica (root) enhanced the growth of DP cells and down-regulated the expression of SRD5A2 in DP cells. Further, plumbagin, an ingredient of P zeylanica, would be responsible for the above effects of P zeylanica. These results suggested the possibility that senescent DP cells may have a role in the development of AGA through up-regulating SRD5A2 expression, and the P zeylanica extract and plumbagin may suppress its development through enhancing the growth of DP cells and down-regulating SRD5A2 expression in DP cells.
Keywords
P zeylanica
- 5α-reductase
- dermal papilla
- hair
- plumbagin
- senescence
A healthy brain is essential for living a longer and fuller life. Detecting asymptomatic white matter hyperintensities (WMHs) may be clinically important in terms of treatment and prognostic evaluation. WMHs in brain may reflect brain aging. Androgenic alopecia (AGA) is associated with significant cardiovascular risk factors that also have a negative impact on brain aging. The main purpose of present study was to know whether alopecia might provide predictive information of WMHs that may be considered as a surrogate marker of cerebral small vessel disease which is related to arteriolosclerosis and vascular risk factors. From January 2017 to March 2018, 256 cases were enrolled consecutively. Patients under 18 years old, older than 90 years old, known to be affected by neurodegenerative diseases, demyelinating disorders or stroke and/or a brain tumor, were excluded from the study. A 4-point cerebral white matter Magnetic Resonance Imaging (MRI) hyperintensities scoring system, the Fazekas scale, was used to evaluate brain aging. Presence of AGA was evaluated with inspection according to Hamilton-Norwood classification system (grade I to VII). Two hundred eleven (82%) of individuals had mild alopecia (grade I, II, III), 28 (11%) had moderate alopecia (grade IV, V) and 17 (7%) had severe alopecia (grade VI, VII). Frequency of abnormal WMHs was significantly higher in patients with AGA compared to the without AGA. Hypertension (HT) (95% confidence interval [CI]: 1.873-9.487, p < 0.001) and the AGA (95% CI: 2.989-12.916, p < 0.0001) were independent determinants of abnormal WMHs. AGA may be regarded as a surrogate marker of asymptomatic WMHs which is related to arteriolosclerosis and vascular risk factors that has a significant impact on people's life.
Keywords
- Androgenic alopecia
- Brain aging
- Fazekas scale
- Hamilton-Norwood scale
ALKB-8 is a 2-oxoglutarate-dependent dioxygenase homologous to bacterial AlkB, which oxidatively demethylates DNA substrates. The mammalian AlkB family contains AlkB homologues denominated ALKBH1 to 8 and FTO. The C. elegans genome includes five AlkB-related genes, homologues of ALKBH1, 4, 6, 7, and 8, but lacks homologues of ALKBH2, 3, and 5 and FTO. ALKBH8 orthologues differ from other AlkB family members by possessing an additional methyltransferase module and an RNA binding N-terminal module. The ALKBH8 methyltransferase domain generates the wobble nucleoside 5-methoxycarbonylmethyluridine from its precursor 5-carboxymethyluridine and its (R)- and (S)-5-methoxycarbonylhydroxymethyluridine hydroxylated forms in tRNA Arg/UCG and tRNA Gly/UCC. The ALKBH8/ALKB-8 methyltransferase domain is highly similar to yeast TRM9, which selectively modulates translation of mRNAs enriched with AGA and GAA codons under both normal and stress conditions. In this report, we studied the role of alkb-8 in C. elegans. We show that downregulation of alkb-8 increases detection of lysosome-related organelles visualized by Nile red in vivo. Reversely, forced expression of alkb-8 strongly decreases the detection of this compartment. In addition, overexpression of alkb-8 applied in a pulse during the L1 larval stage increases the C. elegans lifespan.
MeSH Terms
- Aging
- AlkB Enzymes
- Animals
- Animals, Genetically Modified
- Caenorhabditis elegans
- Caenorhabditis elegans Proteins
- Dioxygenases
- Down-Regulation
- Embryo, Nonmammalian
- Gene Expression Regulation, Developmental
- Green Fluorescent Proteins
- Ketoglutaric Acids
- Larva
- Longevity
- Lysosomes
- Methyltransferases
- Operon
- Promoter Regions, Genetic
- RNA Interference
- S-Adenosylmethionine
To assess the impact of being born preterm or small for gestational age (SGA) on early vascular aging (EVA) in a cohort of healthy Tyrolean adolescents. This study is part of an ongoing clinical trial, EVA Tyrol, a regional cohort study being conducted in western Austria. EVA was assessed in adolescents (mean age, 16 years) by means of carotid-femoral pulse wave velocity (PWV), carotid intima-media thickness (cIMT), and blood pressure measurements. Adolescents were grouped as either term or preterm. Subsequently, being born SGA was taken into consideration in subgroup analysis. Complete data on gestational age and birth weight were available for 930 adolescents. Systolic blood pressure and diastolic blood pressure were significantly higher in the preterm (mean gestational age, 34.8 ± 2.3 weeks) and appropriate for gestational age (AGA) group than in the term and AGA group (P < .05). This finding remained significant in linear regression analysis after adjustment for covariables in all models. PWV was significantly higher in the term-SGA group than in the term-AGA group (6.67 ± 1.73 m/s vs 6.07 ± 1.09 m/s; P < .05). In the linear regression analysis, this finding remained significant in all models. There were no differences in cIMT between study groups. Being born preterm or SGA might render persons susceptible to EVA. Long-term follow-up of preterm and SGA individuals is warranted to confirm these results.
MeSH Terms
- Adolescent
- Austria
- Blood Pressure
- Carotid Artery, Common
- Carotid Intima-Media Thickness
- Cohort Studies
- Female
- Femoral Artery
- Humans
- Infant, Newborn
- Infant, Premature
- Infant, Small for Gestational Age
- Linear Models
- Male
- Pulse Wave Analysis
Keywords
- PWV
- cIMT
- early vascular aging
- preterm
- small for gestational age
Many infants born prematurely experience growth failure following delivery, with subsequent catch-up growth. Traditionally catch-up was thought to be complete in the first few years of life. Most studies have focused on groups of infants defined by birth weight, for example <1500 g, resulting in disproportionate numbers of small for gestational age infants. This study aimed to determine whether appropriate weight for gestation (AGA) preterm born children reach their expected adult height when compared with term controls. This UK based prospective longitudinal cohort study recruited 204 preterm children born at a tertiary neonatal unit during 1994 and 50 matched controls. Growth parameters have been assessed annually until the completion of growth. There was no significant difference in the final height SD score (SDS) of children born at term (n=30) and those born prematurely and AGA (n=70) (0.45 term vs 0.22 preterm). Catch-up growth however, continued throughout the whole of childhood. When the difference between final height SDS and mid-parental height SDS were compared, there were again no significant differences (0.13 term vs 0.03 preterm). Those born prematurely with an AGA achieve a comparable adult height to children born at term, however, catch-up growth continues for much longer than traditionally thought.
MeSH Terms
- Adult
- Aging
- Anthropometry
- Body Height
- Case-Control Studies
- Child Development
- Female
- Gestational Age
- Growth
- Humans
- Infant, Newborn
- Infant, Premature
- Longitudinal Studies
- Male
- Reference Values
- Sex Characteristics
- Term Birth
Keywords
- Growth
- Premature
Physiologically, a reduction in telomere length (LTL) occurs with aging, but epigenetic changes may accelerate telomere shortening and also facilitate the onset of oxidative/inflammatory stress and the development of clinical/metabolic comorbidities in life spam. Although individuals born small for gestational age (SGA) may be related to those epigenetic changes, the assessment of LTL in individuals born SGA has yielded conflicting results (only cross-sectional studies) and has not been carried out in longitudinal studies. We performed a birth cohort study to evaluate the rate of telomere erosion in women born SGA in comparison to women born appropriate for gestational age (AGA) assessed at two different time points during the third decade of life. In our research, born SGA or AGA showed no difference in LTL shortening during a period of five years in the third decade of life. Our finding may have implications for understanding the natural history of diseases in lifespan because the same women (under the influence of similar environmental factors) may be accessed in different phases of life. Thus, the analysis of the present cohort population at a more advanced age may reveal a dynamics of telomere shortening different from here and its possible relation with onset of age-related diseases.
MeSH Terms
- Adult
- Aging
- Birth Weight
- Cohort Studies
- Epigenesis, Genetic
- Female
- Gestational Age
- Humans
- Infant, Newborn
- Infant, Small for Gestational Age
- Leukocytes
- Prospective Studies
- Telomere Shortening
- Young Adult
Keywords
- Epigenetic alteration
- Foetal programming
- Small for gestational age
- Telomere length
Lipids in the skin are the most diverse in the entire human body. Their bioactivity in health and disease is underexplored. Prostaglandin D2 has recently been identified as a factor which is elevated in the bald scalp of men with androgenetic alopecia (AGA) and has the capacity to decrease hair lengthening. An enzyme which synthesizes it, prostaglandin D2 synthase (PTGDS or lipocalin-PGDS), is hormone responsive in multiple other organs. PGD2 has two known receptors, GPR44 and PTGDR. GPR44 was found to be necessary for the decrease in hair growth by PGD2 . This creates an exciting opportunity to perhaps create novel treatments for AGA, which inhibit the activity of PTGDS, PGD2 or GPR44. This review discusses the current knowledge surrounding PGD2 , and future steps needed to translate these findings into novel therapies for patients with AGA.
MeSH Terms
- Alopecia
- Animals
- Humans
- Intramolecular Oxidoreductases
- Lipocalins
- Male
- Prostaglandin D2
Keywords
- aging
- alopecia
- arachidonic acid
- baldness
- hair
- lipids
- prostaglandins
A variety of neurological and psychiatric disorders have recently been linked to coeliac disease and gluten sensitivity. We here explored whether persistently positive gliadin antibodies (AGA) and coeliac-type HLA increase the risk of gluten sensitivity-related neurological and psychiatric manifestations. The study was carried out in an older population who had consumed gluten for decades but who had no previous coeliac disease diagnosis. The original study population comprised 4272 randomly selected older individuals, of whom 2089 had AGA and transglutaminase 2 antibodies (antiTG2) measured twice within a 3-year interval. Forty-nine persistently AGA-positive but antiTG2-negative subjects with coeliac-type HLA and 52 randomly selected persistently AGA- and antiTG2-negative age- and sex-matched controls were clinically examined for neurological disorders. The Psychological General Well-Being (PGWB) questionnaire, the SF-36 health survey questionnaire and the Depression Scale (DEPS) were employed to evaluate psychological well-being. The medical files of all the study subjects were analysed for previous illnesses. Persistently AGA-positive but antiTG2-negative older subjects carrying coeliac disease-type HLA did not evince significantly more neurological symptoms or diseases than AGA-negative control subjects (P = 0.682, P = 0.233). There were no statistically significant differences between AGA-positive and AGA-negative groups in psychological well-being and quality of life when measured by PGWB (P = 0.426), SF-36 questionnaires (P = 0.120) and DEPS (P = 0.683). At population level, persistent AGA positivity did not indicate gluten sensitivity-related neurological and psychiatric disorders.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Antibodies
- Endoscopy, Gastrointestinal
- Enzyme-Linked Immunosorbent Assay
- Female
- Gliadin
- HLA-DQ Antigens
- Histocompatibility Testing
- Humans
- Male
- Mental Disorders
- Mental Status Schedule
- Middle Aged
- Mucus
- Nervous System Diseases
- Neurologic Examination
- Statistics, Nonparametric
Adipose tissue seems to be a pivotal organ in the aging process. We investigated whether healthy aging could have its roots in a sound metabolic condition from the first year of life by evaluating leptin and adiponectin levels in neonates [33 adequate for gestational age (AGA) and 29 small for gestational age (SGA)], 48 centenarians, and 50 healthy elderly subjects. At birth, SGA neonates showed lower leptin levels (SGA 0.88 /- 0.28; AGA 2.22 /- 0.91 ng/mL; p < 0.05) and comparable adiponectin levels with respect to AGA. At 1 year, SGA showed increased leptin (SGA 1.74 /- 0.28; AGA 1.31 /- 0.19 ng/mL) and slightly reduced adiponectin concentrations (SGA 35.51 /- 2.53; AGA 38.56 /- 3.18 microg/mL) than AGA. Centenarians showed lower leptin (centenarians 18.71 /- 3.78; elderly 34.81 /- 7.27 ng/mL; p < 0.05) and higher adiponectin levels (centenarians 55.63 /- 7.7; elderly 33.51 /- 4.1 microg/mL; p < 0.05) than elderly subjects. Centenarians, like AGA infants during the first year of life, show a favorable adipokine profile, suggesting that the metabolic condition at early age could affect the longevity of an individual.
MeSH Terms
- Adiponectin
- Adipose Tissue
- Aged
- Aged, 80 and over
- Aging
- Birth Weight
- Energy Metabolism
- Female
- Humans
- Infant, Low Birth Weight
- Infant, Newborn
- Infant, Small for Gestational Age
- Leptin
- Male
Although severely preterm birth has been associated with impaired neurocognitive abilities in children, follow-up studies in adulthood are scarce. We set out to study whether adults born with very low birth weight (VLBW) (<1,500 g), either small for gestational age (SGA) (birth weight ≤-2 SD) or appropriate for gestational age (AGA), differ in a range of neurocognitive abilities and academic performance from adults born at term and not SGA. As part of the Helsinki Study of Very Low Birth Weight Adults, 103 VLBW (37 SGA) and 105 term-born control adults (mean age 25.0, range 21.4-29.7 years) without major neurosensory impairments participated in the follow-up study in 2007-2008. The test battery included measures of general cognitive ability as well as executive functioning and related abilities. Academic performance was self-reported. With adjustment for sex and age, the VLBW group scored lower or performed slower than the control group in some indices of all tests (these mean differences ranged from 0.3 to 0.5 SD units, p ≤ 0.03) and they had received remedial education at school more frequently; however, no differences existed in self-reported academic performance. The differences were evident in both VLBW-SGA and VLBW-AGA groups. Further covariate adjustments for parental education, current head circumference, and head circumference at birth and, in tests of executive functioning and related abilities, adjustment for IQ estimate had minor effects on the results. In comparison with control adults, VLBW adults scored lower on several neurocognitive tests. Poorer neurocognitive performance is associated with VLBW irrespective of the intrauterine growth pattern.
MeSH Terms
- Adult
- Aging
- Case-Control Studies
- Cognition
- Female
- Follow-Up Studies
- Humans
- Infant, Newborn
- Infant, Very Low Birth Weight
- Male
- Neuropsychological Tests
- Young Adult
Controversies exist regarding the association of androgenetic alopecia (AGA) with insulin resistance. Are they truly associated, or is insulin resistance just related to aging, obesity, or to the presence of metabolic syndrome? To assess insulin resistance in young nonobese patients with AGA with and without metabolic syndrome. The study included four equally distributed groups of age-, sex-, and body mass index-matched young, nonobese subjects: 30 patients with AGA and metabolic syndrome (group 1); 30 patients with AGA and no metabolic syndrome (group 2); 30 patients with metabolic syndrome and no AGA (group 3); and 30 healthy controls (group 4). Insulin resistance based on fasting insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR) was assessed in all groups. Twenty-three patients in group 1, four patients in group 2, 25 patients in group 3, and three healthy controls had insulin resistance with statistically significant differences in fasting insulin and HOMA-IR levels between all groups, between groups 1 and 2, groups 1 and 4, groups 2 and 3, and groups 3 and 4. No significant differences existed between groups 2 and 4 or groups 1 and 3. Correlations between insulin resistance parameters, age of patients, disease duration, and stages of AGA in males and females revealed nonsignificant differences. Patients with metabolic syndrome, with or without AGA, were significantly more insulin resistant compared with patients with AGA with no metabolic syndrome and with healthy subjects and, therefore, no true association exists between AGA and insulin resistance.
MeSH Terms
- Adult
- Aging
- Alopecia
- Body Mass Index
- Case-Control Studies
- Female
- Homeostasis
- Humans
- Insulin
- Insulin Resistance
- Male
- Metabolic Syndrome
- Obesity
- Young Adult
Preterm infants are at risk of developing insulin resistance. It is not known whether insulin resistance in adult life is different between those with a low weight at term (preterm growth restraint, PGR) and those with a normal weight at term. Insulin sensitivity, measured by the hyperinsulinemic euglycemic clamp, was investigated in 21-year-old adults born very preterm (i.e. <32 gestational weeks), of whom 17 were small for gestational age (SGA), 12 were appropriate for gestational age with PGR (AGA-PGR) and 28 were AGA-non-PGR. Insulin sensitivity expressed as M value (glucose disposal mg/kg/min) was lower in AGA-non-PGR (8.9) than in SGA (11.0) or AGA-PGR subjects (10.4). These differences disappeared after adjustment for current body size. Linear growth between 3 months and 21 years of age was different between AGA-non-PGR and SGA subjects and between AGA-nonPGR subjects and the combined AGA-PGR and SGA subjects. In young adults born very preterm, differences in insulin sensitivity between those born SGA, with PGR and without PGR are related to the current body composition.
MeSH Terms
- Aging
- Birth Weight
- Body Composition
- Body Mass Index
- Body Size
- Female
- Fetal Growth Retardation
- Follow-Up Studies
- Glucose Clamp Technique
- Humans
- Infant, Newborn
- Infant, Small for Gestational Age
- Insulin Resistance
- Male
- Netherlands
- Premature Birth
BACKGROUND /AIM: It has been shown previously that in primary care settings in UK abnormal liver enzymes are not adequately investigated and followed up; hence potentially treatable chronic liver diseases remain undiagnosed. No such published data is available with regard to secondary care settings. The aims of this audit were, to determine if the current practice in our hospital with regards to investigation, management and follow-up of patients with elevated liver enzymes is in accordance with American Gastroenterology Association (AGA) guidelines and to analyze the effect of age and elevated parameters of liver blood tests on mortality in patients with bacterial sepsis . A total of 4816 patients were admitted to our acute medical receiving unit during a period of 6 months, of which 378 were with elevated liver enzymes. The common conditions that resulted in elevated liver enzymes were sepsis (123) and alcohol-related liver diseases (120). All patients with elevated parameters of liver function tests (LFTs) were fully investigated, managed and followed up in accordance with AGA guidelines. In addition, in patients with bacterial sepsis, old age was associated with increased mortality, while development of jaundice in elderly patients with bacterial sepsis was associated with increased survival.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Alanine Transaminase
- Aspartate Aminotransferases
- Clinical Enzyme Tests
- Guideline Adherence
- Humans
- Jaundice
- Liver
- Liver Diseases
- Liver Diseases, Alcoholic
- Liver Function Tests
- Middle Aged
- Sepsis
- Young Adult
Studies indicate that women born small for gestational age (SGA) have impaired ovarian function. The origin of this ovarian dysfunction is still debatable. The aim of this study was to compare ovarian ageing between girls born appropriate for gestational age (AGA) and SGA. Therefore, we measured Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), E2, Anti-Müllerian hormone (AMH) levels and the pituitary response to endogenous Gonadotropin-releasing hormone (GnRH) in adolescent girls born SGA and AGA. A case-controlled pilot study consisting of seven SGA women (birth weight < 10th percentile AGA) and 13 AGA women with regular menstrual cycles, age 19.9 ± 0.42). Early follicular FSH, LH, Oestradiol (E2) and AMH levels were measured. After baseline samples, 100 μg GnRH was administered intravenously and at 30, 60 and 90 min blood samples were taken to measure gonadotropin levels and to compute the response to endogenous GnRH. Mean follicular phase LH, FSH, E2 and AMH levels did not significantly differ between young women born SGA and AGA. Furthermore, the response to endogenous GnRH showed no significant differences either. We concluded against extension of this pilot study. Based on our observations it seems unlikely that limited ovarian reserve is a predominated problem in adolescent SGA.
MeSH Terms
- Adolescent
- Aging
- Anti-Mullerian Hormone
- Birth Weight
- Case-Control Studies
- Estradiol
- Female
- Follicle Stimulating Hormone
- Gonadotropin-Releasing Hormone
- Humans
- Luteinizing Hormone
- Ovary
- Pilot Projects
- Pituitary Gland
- Puberty
- Young Adult
Antigliadin antibodies (AGA) show good sensitivity but low specificity for celiac disease and can also be found in healthy individuals. However, data suggest that AGA positivity might be related to distinct disease entities such as allergy and gluten ataxia. Our aim here is to explore the clinical relevance of positive AGA in the elderly population. Serum IgA- and IgG-class AGA and IgA-class tissue transglutaminase antibodies (tTGA) were determined in 2815 individuals aged 52-74 years. Equal numbers of AGA- and tTGA-negative participants of similar age and gender, but without known celiac disease, were randomly selected as controls. Information on clinical history was obtained from hospital records in all groups. Altogether 381 persons were positive for IgA/IgG-class AGA; 38 (14%) of them were also positive for tTGA. Out of the biopsied subjects, 34 (100%) in the AGA tTGA group and five (9%) in AGA tTGA- group had celiac disease. Rheumatoid arthritis and depression were found significantly more often in AGA-positives than controls. The significance remained even when tTGA-positive and known celiac disease cases were excluded. No statistical differences were found in the occurrence of neurological diseases, diabetes, allergic and cardiovascular diseases or malignancies. Although AGA positivity is of clinical relevance only in a subset of elderly people, it seems to be related to rheumatoid arthritis and depression, both conditions linked to celiac disease. Further studies are needed to reveal the mechanisms underlying this. The poor specificity of AGA for celiac disease was here once more in evidence.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Arthritis, Rheumatoid
- Autoantibodies
- Biomarkers
- Case-Control Studies
- Celiac Disease
- Depression
- Diagnosis, Differential
- Female
- Fluorescent Antibody Technique
- Gliadin
- Humans
- Immunoglobulin A
- Immunoglobulin G
- Immunologic Factors
- Male
- Middle Aged
- Predictive Value of Tests
- Sensitivity and Specificity
Measurements at the end of puberty of neonates short for gestational age (SGA-L) are scant. To determine the correlation between birth length and weight in neonates, with height and weight at age 17 years. 385 full-term neonates, measuring less than 48 cm (SGA-L) and 585 full-term neonates, measuring 48 cm or greater (adequate birth length for gestational age; AGA-L) were included. 234 SGA-L and 359 AGA-L were identified at age 17 years. Comparison of the two groups revealed that both sexes born SGA-L were also shorter at age 17 years than those born AGA-L (girls 158.9 cm (SD 7.6) vs 164.2 cm (SD 64) (p<0.001) and boys 167.3 cm (SD 8.7) vs 173.8 cm (SD 7.1) (p<0.001)). The subjects born SGA-L also weighed significantly less than those born AGA-L (p<0.001) both at birth and at age 17 years. Children born SGA-L become short adults and weigh less at age 17 years than children with a normal birth length.
MeSH Terms
- Adolescent
- Adolescent Development
- Aging
- Anthropometry
- Birth Weight
- Body Height
- Body Weight
- Child Development
- Female
- Humans
- Infant, Newborn
- Infant, Small for Gestational Age
- Male
- Retrospective Studies
Chemokine (C-C-motif) receptor 3 (CCR3), playing an important role in endometrium related metabolic pathways, may influence the onset of menarche. To test linkage and/or association between CCR3 polymorphisms with the variation of age at menarche (AAM) in Caucasian females, we recruited a sample of 1,048 females from 354 Caucasian nuclear families and genotyped 16 SNPs spanning the entire CCR3 gene. Linkage disequilibrium and haplotype blocks were inferred by Haploview. Both single-SNP markers and haplotypes were tested for linkage and/or association with AAM using QTDT (quantitative transmission disequilibrium test). We also tested associations between CCR3 polymorphisms and AAM in a selected random sample of daughters using ANOVA (analysis of variance). We identified two haplotype blocks. Only block two showed significant results. After correction for multiple testing, significant total associations of SNP7, SNP9 with AAM were detected (P = 0.009 and 0.006, respectively). We also detected significant within-family association of SNP9 (P = 0.01). SNP14 was linked to AAM (P = 0.02) at the nominal level. In addition, there was evidence of significant total association and nominal significant linkage (P = 0.008 and 0.03, respectively) with AAM for the haplotype AGA reconstructed by SNP7, SNP9 and SNP13. ANOVA confirmed the results by QTDT. For the first time we reported that CCR3 is linked and associated with AAM variation in Caucasian women. However, further studies are necessary to substantiate our conclusions.
MeSH Terms
- Aging
- Alleles
- Amino Acid Motifs
- Endometrium
- European Continental Ancestry Group
- Female
- Genetic Linkage
- Humans
- Male
- Menarche
- Polymorphism, Single Nucleotide
- Random Allocation
- Receptors, CCR3
- Receptors, Chemokine
To evaluate the metabolic pattern of a group of pre-school small- (SGA) and appropriate-for-gestational age (AGA) pre-term very-low-birthweight (VLBW) (<1500 gr) Italian children and retrospectively verify if the growth rate in the first years of life is associated to the laboratory and anthropometric characteristics of these children. 58 (16 SGA, 42 AGA) VLBW children, without major congenital malformations/conditions were enrolled; their anthropometric, clinical and (in 34 of them) laboratory characteristics were evaluated at pre-school age (> 2<6 years of corrected age). Clinical, anthropometric and laboratory characteristics at pre-school age were similar in SGA and AGA. Sixty-nine percent of SGA and 51% of AGA children showed a significant weight centile crossing (CC) at 24 months. Fasting serum glucose, insulin and insulin resistance (evaluated by the Homeostasis Model Assessment -HOMA-IR-) were higher in AGA and SGA with CC. The increment in weight standard deviation scores from birth-to-24 months was significantly associated with pre-school BMI SDS, waist, fasting insulin, and HOMA-IR values, both in unadjusted and adjusted models. In a multiple regression model, after multiple adjustments, this increment is the only significant predictor of pre-school insulin (B = 0.19; 95%CI 0.07-0.31; P = 0.006) and HOMA-IR levels (B = 0.20; 95%CI 0.08-0.32; P = 0.004) both in SGA and AGA children. The adverse metabolic pattern of pre-school VLBW children seems related to post-natal events (rapid weight growth) independently by their being small- or appropriate-for gestational age.
MeSH Terms
- Aging
- Body Mass Index
- Child, Preschool
- Cohort Studies
- Diabetes Mellitus
- Family
- Female
- Humans
- Infant, Newborn
- Infant, Premature
- Infant, Small for Gestational Age
- Infant, Very Low Birth Weight
- Insulin Resistance
- Male
- Parents
The aims of this study were to establish the role of insulin resistance in the metabolic syndrome associated with restricted fetal growth and to characterise the fetal and postnatal determinants responsible for the long-term metabolic outcome. The study population consisted of adults selected on birth data from a maternity registry and born either small for gestational age (SGA) (n=734, birthweight<tenth percentile) or appropriate for gestational age (AGA) (n=886, 25th<birthweight<75th percentile) and in whom clinical and metabolic parameters of the metabolic syndrome were measured at 22 years of age. Mean values of all components of the metabolic syndrome significantly differed between the two groups, with the metabolic syndrome observed in 2.3% of the SGA group and in 4 per thousand of the AGA group (p=0.0004). In SGA subjects, the upper tertile of fasting insulinaemia was associated with the highest values of systolic (p=0.001) and diastolic (p=0.02) blood pressure, triglyceridaemia (p=0.005) and glycaemia at fasting (p=0.0001) and during OGTT (p=0.0001). In SGA subjects, insulin resistance was not related to birthweight itself (p=0.26), but correlated negatively with BMI at birth (p=0.03) and positively with the subsequent postnatal catch-up in BMI (p=0.009). Insulin resistance is the keystone of metabolic syndrome associated with SGA, and its origin should be sought in the fetal development process of adiposity that is responsible for postnatal growth and the later development of insulin resistance.
MeSH Terms
- Adipose Tissue
- Adult
- Aging
- Birth Weight
- Blood Glucose
- Blood Pressure
- Body Mass Index
- Fetal Development
- Fetal Growth Retardation
- France
- Gestational Age
- Humans
- Infant, Newborn
- Infant, Small for Gestational Age
- Insulin
- Insulin Resistance
- Lipids
- Metabolic Syndrome
- Registries
Seventy-five small for gestational age (SGA) children were studied in a randomized, double-blind, dose-response GH trial with either 1 or 2 mg GH/m(2).d. Mean (SD) age at the start of GH therapy was 7.3 (2.2) yr. Data were compared with Dutch reference data. In SGA boys, mean (SD) age at onset of puberty was 12.0 (1.0) and 11.6 (0.7) yr, and in SGA girls it was 10.9 (1.1) and 10.6 (1.2) yr when treated with 1 and 2 mg GH/m(2).d, respectively. SGA boys treated with the lower GH dose started puberty later than the appropriate for gestational age (AGA) controls; for the other GH-dosage groups there was no significant difference in age at onset of puberty compared to AGA controls. The age at menarche and the interval between breast stage M2 and menarche were not significantly different for GH-treated SGA girls compared to their peers. The duration of puberty and pubertal height gain of GH-treated SGA boys and girls were not significantly different between the two GH-dosage groups and were comparable with untreated short children born SGA. In conclusion, long-term GH therapy in short SGA children has no influence on the age at onset and progression of puberty compared to AGA controls, regardless of treatment with a dose of 1 or 2 mg GH/m(2).d. Duration of puberty and pubertal height gain were not significantly different between the GH-dosage groups.
MeSH Terms
- Aging
- Body Height
- Child
- Dose-Response Relationship, Drug
- Double-Blind Method
- Female
- Growth Hormone
- Human Growth Hormone
- Humans
- Infant, Newborn
- Infant, Small for Gestational Age
- Male
- Menarche
- Puberty
- Time Factors
Insulin secretion and sensitivity was studied in 28 prepubertal children born small for gestational age (SGA) and in 22 prepubertal children born appropriate for gestational age (AGA). The effect of body size during childhood was also assessed. Insulin sensitivity was measured using the hyperinsulinemic-euglycemic clamp (M value), and beta-cell function was studied with the hyperglycemic clamp plus arginine. First-phase insulin response (FIR) was used to calculate the disposition index (FIR x M value). Arginine-stimulated second-phase insulin response was used as a measure of beta-cell capacity. DeltaBMI(0-1 year), DeltaBMI(0-2 years), and DeltaBMI(2-9 years) were classified in tertiles. SGA children were less insulin sensitive than AGA children (P = 0.009). beta-Cell capacity and disposition indexes were similar in the two groups. In SGA children, M values were lower in the tertile with the highest DeltaBMI(2-9 years) than in the tertile with the lowest DeltaBMI(2-9 years) (P = 0.01). No association between DeltaBMI(0-2 years) and decreased insulin sensitivity was found. In conclusion, prepubertal SGA children show decreased insulin sensitivity rather than decreased beta-cell capacity. Interventions to improve fetal growth and prevent overweight after the second year of life appear to be important factors in the prevention of type 2 diabetes in children born SGA.
MeSH Terms
- Aging
- Arginine
- Birth Weight
- Body Constitution
- Body Mass Index
- Child
- Female
- Growth
- Humans
- Infant, Newborn
- Infant, Small for Gestational Age
- Insulin
- Insulin Secretion
- Islets of Langerhans
- Male
Wide ranges in postnatal weight gain are seen in infants born small for gestational age (SGA); most show some catch-up growth and this may be driven by increased appetite. Ghrelin, the natural ligand of the GH secretagogue receptor, has potent orexigenic effects. In adults circulating ghrelin levels are increased in anorexia, decreased in obesity and show post prandial suppression. The aim of the present study was to test the hypothesis that rate of weight gain over the first year in SGA infants may relate to variable suppression of circulating ghrelin levels. Serum ghrelin levels were measured in 1 y old infants born SGA (n = 85) and in control infants born adequate for gestatitional age (AGA) (n = 22) fasting and 10 minutes after intravenous (iv) glucose (0.5 g/Kg of 25% dextrose). Sex- and gestational age-adjusted SD scores (SDS) for body weight were calculated at birth and at 1 y, and delta weight SDS between 0-1 y was calculated as an index of postnatal weight gain. In both SGA and AGA groups, ghrelin levels reduced from fasting (mean /- SE: 104.4 /- 6.4 fmol/ml) to 10 minutes post-iv glucose (82.7 /- 5.3, p < 0.005). There were no differences in ghrelin levels between SGA and AGA infants (fasting or post-iv glucose). However, in SGA infants ghrelin levels post-glucose, but not fasting, were psitively related to current length (r = 0.28, p < 0.05), weight (r = 0.23, p < 0.05) and to change in weight SDS 0-1 y (r = 0.22, p < 0.05). SGA infants who showed poor catch-up growth showed a larger decline in ghrelin concentrations post-iv glucose. In conclusion, circulating ghrelin levels rapidly decreased after iv glucose. Higher ghrelin levels or lower reductions in circulating levels following iv glucose were seen in SGA infants who showed greater infancy weight gain, suggesting that sustained orexigenic drive could contribute to postnatal catch-up growth.
MeSH Terms
- Aging
- Body Constitution
- Fasting
- Ghrelin
- Glucose
- Humans
- Infant, Newborn
- Infant, Small for Gestational Age
- Injections, Intravenous
- Peptide Hormones
- Weight Gain
Leptin is involved in the regulation of body weight through a feedback signal between adipose tissue and the satiety center, to decrease food intake and increase energy expenditure. Newborn infants experience physiological weight loss during the first week of life. The leptin level may be decreased to enhance food intake and to decrease energy expenditure for physiological adaptation during early postnatal days. Insulin-like growth factor-I (IGF-I) and insulin are involved in the regulation of perinatal growth. Leptin might be interrelated with IGF-I or insulin, since both of these have adipogenic and somatotropic effects. We therefore hypothesized that leptin, IGF-I and insulin would be decreased during the first week of life, concurrently with physiological weight loss. Thirty preterm AGA infants (birth weight 1.574 /-313 g; GA 31.9 /-2.2 wk) were studied. All infants received parenteral nutrition from the third day after birth. Leptin was significantly decreased during the first week of life, and insulin was significantly increased at day 7 vs. day 1 and day 3. IGF-I did not change during the first week of life. Leptin was positively correlated with body weight (r = 0.368, p<0.01), body mass index (r = 0.267, p<0.05), and serum IGF-I (r = 0.330, p <0.01), but not with serum insulin. The percent of weight reduction during the first week of life was not correlated with the percent of leptin reduction during the first week of life. In conclusion, leptin was significantly decreased and positively correlated with body weight and IGF-I during the first week of life. Changes of leptin and insulin might be related to postnatal adaptation in metabolism, but the exact role of leptin, IGF-I and insulin in postnatal physiological weight loss is not clear.
MeSH Terms
- Aging
- Body Mass Index
- Female
- Gestational Age
- Humans
- Infant, Newborn
- Infant, Premature
- Insulin
- Insulin-Like Growth Factor I
- Leptin
- Male
- Parenteral Nutrition
- Weight Loss
In order to optimize the nutrition of high-risk premature infants beyond the early postnatal period, a more precise knowledge of individual nutritional requirements is needed. We therefore studied the influence of intrauterine growth retardation on energy expenditure and nutrient utilization determined by indirect calorimetry and fecal fat excretion (steatocrit) in nineteen premature infants who were appropriate-for-gestational-age (AGA; mean gestational age 29.9 /-0.3 weeks, mean birth weight 1.30 /-0.05 kg) and thirteen small-for-gestational-age (SGA) premature infants [mean gestational age 32.4 /-0.5 weeks, mean birth weight 1.024 /-0.07 kg (i.e., below the 10th percentile)] during the first and second month of life. All infants were clinically stable during the study period. In nine SGA infants we observed a significantly higher steatocrit compared to twelve AGA infants (29 /-1 vs. 17 /-1% p = 0.0001). SGA infants (n = 12) also showed a slightly (albeit statistically not significantly) higher energy expenditure than AGA infants (n = 15) (58.7 /-1.9 vs. 53.6 /-1.5 kcal/kg per day, p = 0.054). Despite the increased fat excretion and higher energy expenditure, SGA infants gained weight more rapidly during the study period than AGA infants (20 /-1 vs. 17 /-1 g/kg per day, p = 0.026). We conclude that influences of intrauterine growth retardation on energy expenditure and nutrient utilization persist during the first weeks of extrauterine life. However, these metabolic changes do not impair the capability of SGA infants for extrauterine catch-up growth if adequate nutrition is provided.
MeSH Terms
- Aging
- Birth Weight
- Energy Metabolism
- Feces
- Fetal Growth Retardation
- Humans
- Infant
- Infant, Newborn
- Infant, Small for Gestational Age
- Lipids
- Oxygen Consumption
- Weight Gain
The product of the obese (ob) gene, leptin, is an adipocyte-derived hormone that is involved in the regulation of appetite and body weight. This study was undertaken in order to describe the basal serum levels of leptin in prepubertal short children born small for gestational age (SGA) and their relationship with growth parameters, before and during growth hormone (GH) treatment. Eighty-nine prepubertal short children (66 boys, 23 girls; height standard deviation score (SDS), -5.4 to -2.0; age, 2.0 to 12.8 years) born SGA, 12 of whom (9 boys, 3 girls) had signs of Silver-Russell syndrome, were included in the study. Serum leptin concentrations were measured by radioimmunoassay. Leptin levels in the children born SGA were compared with those in a reference group of 109 prepubertal healthy children born at an appropriate size for gestational age (AGA). The mean (S.D.) change in height SDS was 0.11 (0.22) during the year before the start of GH therapy (0.1 IU/kg/day) and increased to 0.82 (0.44) during the first year (P < 0.001) and to 1.28 (0.59) during the 2-year period of GH therapy (P < 0.001). The children born SGA were significantly leaner than the reference group. An inverse correlation was found between leptin and chronological age in the SGA group (r = -0.31, P < 0.01). The mean serum level of leptin in the children born SGA who were older than 5.5 years of age was 2.8 micrograms/l which was significantly lower than the mean value of 3.7 micrograms/l found in the children born AGA of the same age range. The difference remained after adjustment of leptin levels for sex, age, body mass index (BMI) and weight-for-height SDS (WHSDSSDS). Leptin correlated with WHSDSSDS (r = 0.32, P < 0.001) and BMI (r = 0.36, P < 0.01) in the reference population, but not in the SGA group. No correlation was found between leptin and spontaneous 24-h GH secretion, insulin-like growth factor (IGF)-I or IGF-binding protein-3 levels, or with fasting insulin or cortisol levels. Leptin levels at the start of GH treatment were correlated with the growth response over both 1 year (r = 0.46, P < 0.001) and 2 years (r = 0.51, P < 0.001) of GH therapy. Using multiple regression analysis, models including leptin levels at the start of GH therapy could explain 51% of the variance in the growth response after 1 year and 44% after 2 years of GH treatment. In conclusion, serum leptin levels are reduced in short children born SGA and are inversely correlated with chronological age. Leptin concentrations correlate with the growth response to GH treatment and might be used as a marker for predicting the growth response to GH treatment.
MeSH Terms
- Aging
- Body Height
- Body Mass Index
- Body Weight
- Child
- Child Development
- Child, Preschool
- Cohort Studies
- Female
- Growth Hormone
- Hormones
- Human Growth Hormone
- Humans
- Infant, Small for Gestational Age
- Leptin
- Male
- Osmolar Concentration
- Proteins
- Reference Values
- Sex Characteristics
The objective of this study was to measure serum IGF-I, IGFBP-3, copper and zinc levels and to analyze their relationship to perinatal growth. Serum IGF-I (RIA after acid-ethanol extraction), IGFBP-3 (RIA), copper and zinc (atomic absorption spectrophotometry) levels were measured in cord blood (n = 78) and in newborn children 1 (n = 110) and 3 (n = 42) weeks after birth. Anthropometric variables were measured and the weekly average intake of energy and nutrients were calculated. We found that IGF-I and zinc levels during the 1st week of postnatal life were lower in fullterm LGA and AGA and in preterm (PT) AGA infants than in cord blood. The highest IGF-I levels were obtained in LGE fullterm infants (37.9 /- 29.5 ng/mL) and the lowest in SGA preterm infants (9.3 /- 10.3 ng/mL). Serum zinc levels in preterm neonates continued decreasing at the 3rd week after birth. However, IGF-I and IGFBP-3 levels increased significantly (IGF-I: 13.2 /- 15.5 vs 34.5 /- 27.3 ng/mL, p < 0.01; IGFBP-3: 364.3 /- 185.1 vs 634.1 /- 306.9 ng/mL, p < 0.01). Serum copper levels in the control group increased in relationship to the levels found at the 1st week of life, while this increase neither happened in fullterm SGA infants nor in preterm infants. A positive relationship was found between IGF-I and IGFBP-3. Both were directly connected to energy and protein intake. We conclude that intrauterine over-nutrition is related to higher IGF-I levels, whereas prematurity and intrauterine growth retardation are associated with lower zinc, IGF-I and IGFBP-3 levels and with a lack of increase in copper serum levels.
MeSH Terms
- Aging
- Copper
- Fetal Blood
- Gestational Age
- Humans
- Infant, Low Birth Weight
- Infant, Newborn
- Infant, Premature
- Insulin-Like Growth Factor Binding Protein 3
- Insulin-Like Growth Factor I
- Zinc
Human erythrocyte superoxide dismutase (SOD) was purified and specific antiserum was raised in rabbits. Enzyme preparations from adults and from newborns were shown to be indistinguishable in their immunologic and electrophoretic properties. Erythrocyte SOD was quantitated in blood specimens from adults and in cord blood specimens from neonates of different gestational ages, using both an immunologic and an activity assay. The mean values of SOD concentration and SOD activity for adults and for newborns of average size for gestational age (AGA) showed no significant difference. Adult red cells contained 28.0 /- 8.3 SOD units/mg hemoglobin (Hgb) whereas AGA neonatal red cells had 28.5 /- 8.3 SOD units/mg Hgb. Immunologic quantitation by single radial immunodiffusion revealed 0.69 /- 0.07 micrograms SOD/mg Hgb in adults and 0.70 /- 0.14 micrograms SOD/mg Hgb in the AGA neonates; however, the SOD concentrations from both small for gestational age (SGA) and large for gestational age (LGA) neonates were significantly lower than those of the AGA neonates and the adults (SGA: 0.57 /- 0.24 micrograms SOD/mg Hgb, P less than 0.05; LGA: 0.59 /- 0.16 micrograms SOD/mg Hgb, P less than 0.05).
MeSH Terms
- Adult
- Aged
- Aging
- Erythrocytes
- Fetal Blood
- Gestational Age
- Humans
- Immunodiffusion
- Immunoelectrophoresis
- Infant, Newborn
- Middle Aged
- Superoxide Dismutase
Brainstem auditory evoked potentials (BAEPs) were recorded from 39 preterm infants, divided into 3 groups: small-for-gestational-age, with a birthweight less than or equal to 1500 g (SGA); appropriate-for-gestational-age, with a birthweight less than or equal to 1500 g (AGA1); and appropriate-for-gestational-age, with a birthweight higher than 1500 g (AGA2). A significant shortening of the I-V interval due to an increase in wave I latency was found in the SGA group. The lower-weight AGA group (AGA1) was never significantly different from the SGA group. Although there was no correlation between conceptional age and weight at the time of the examination for the studied population, negative correlations were found between wave I latency and weight at the time of the examination. These findings confirm previous research and suggest the existence of a link between weight and basal cochlear maturation.
MeSH Terms
- Acoustic Stimulation
- Aging
- Birth Weight
- Cochlea
- Evoked Potentials, Auditory, Brain Stem
- Female
- Gestational Age
- Humans
- Infant, Newborn
- Infant, Premature
- Infant, Small for Gestational Age
- Male