bluuebunny/crossref_metadata_2025 huggingface dataset:
Perinatal risk factors and neuromotor behaviour during the neonatal period
Authors: Katz‐Salamon M. , Allert K. , Bergström B‐M , Ericsson K. , Hesser U. , Forssberg H.
Published: March 2012

Preterm birth is associated with an increased risk for neurological handicaps. The purpose of the present study has been: to investigate the influence of perinatal risk factors on early neuromotor development during the neonatal period; to specify the neuromotor parameters particularly sensitive to perinatal complications; and to analyse whether the infant's age at test influences the results. Bedside examination of passive/active muscle tone and automatic movements (22 parameters) was performed at 36 (101 infants) and 40 (153 infants) gestational weeks. Low birthweight and long treatment on a ventilator had a negative influence on the neuromotor behaviour at 36 weeks' gestation and white matter disturbances strongly affected the neuromotor parameters at 40 weeks. The development of rooting, sucking, swallowing and arm recoil after long‐lasting ventilator treatment was affected by several neonatal risk factors. The development of passive muscle tone and several parameters measuring active muscle tone demonstrated individual consistency between tests, i.e. an infant's rank at 36 weeks' gestation was unchanged 4 weeks later, and some other parameters were not as consistent. The present study shows that several perinatal risk factors influence neuromotor behaviour already during the neonatal period. In addition, the present study provides data on the neuromotor behaviour during the neonatal period that will be related to later neurodevelopmental examinations in order to evaluate the prognostic value of testing neuromotor development.
Interaction between timing of perinatal human immunodeficiency virus infection and the design of preventive and therapeutic interventions
Authors: Mofenson LM
Published: March 2012

In 1994, the hypothesis that transmission of human immunodeficiency virus (HIV) from mother to child could be interrupted became a reality when it was shown that a regimen of zidovudine given to HIV‐infected pregnant women and their newborn infants could reduce the risk of perinatal transmission by two‐thirds. An understanding of the pathogenesis of transmission is crucial for interpreting these results, for design of future interventions and for understanding the natural history of perinatal HIV infection. This paper will review current information regarding the timing of and risk factors for perinatal HIV transmission, and the relationship between the timing of transmission and design of efforts to interrupt transmission and to slow disease progression in infected infants.
Epidemiology of HIV/AIDS in women and children in the USA
Authors: Rogers MF
Published: March 2012

In the USA, the AIDS epidemic has shown dramatic increases among women and children in the past decade with more than 70 000 cases in women and 7000 cases in children reported. Acquired immunodeficiency syndrome is the seventh leading cause of death in children aged 1–4 years and the fourth leading cause of death among women aged 25–44 years. Data from the National Survey of Childbearing Women, a blinded serosurvey of blood specimens left over from routine metabolic screening of most infants born in the USA, indicate that approximately 7000 HIV‐infected women have given birth each year for the past several years. Human immunodeficiency virus infection disproportionately affects African‐Americans and women of Hispanic ethnicity. Most cases in women and children have come from states along the east coast and large urban areas. Pneumocystis carinii pneumonia (PCP) continues to be the most commonly reported opportunistic infection in children with AIDS. As of 31 December, 1995, 2383 cases of PCP had been reported to the Centers for Disease Control and Prevention. Revised guidelines for PCP prophylaxis published in 1995 will hopefully provide a better means for preventing this deadly infection in children with AIDS. In 1994, a clinical trial (ACTG 076) found that the risk of perinatal transmission could be reduced by two‐thirds with the use of a zidovudine regimen given antenatally, during labor and delivery, and postnatally to the infant. The US Public Health Service published guidelines based on these results, recommending voluntary HIV counseling and testing for all pregnant women in the USA and zidovudine therapy for those women found to be HIV‐infected. Since implementation of these guidelines, cases of perinatally acquired AIDS in children have begun to decrease. Adequate resources for provision of care, outreach to women who do not receive prenatal care, training of healthcare personnel and attention to the many social and psychological needs of HIV‐infected women and their children are key factors for further reduction of HIV infection in children.
Role of placental cytokines and inflammation in vertical transmission of HIV infection
Authors: Shearer WT , Reuben J. , Lee B‐N , Popek EJ , Lewis DE , Hammill HH , Hanson IC , Kline MW , Langston C.
Published: March 2012

In light of new evidence suggesting that maternal human immunodeficiency virus (HIV) infection produces at least a three‐fold increase in the number of early spontaneous abortions, it is important to search for factors that may predispose to fetal wastage. Immunological factors are thought to play an important role in permitting the HLA‐disparate fetus to continue to term, despite powerful maternal immune forces capable of rejection. In the context of a heightened incidence of spontaneous abortion in HIV infection, evidence is now accumulating that implicates an imbalance in immune factors in contributing to this fetal loss. Soluble immune factors, such as cytokines, have been suggested as contributing agents to recurrent spontaneous abortions. Inflammatory cytokines—interleukin 1β, interleukin 6 and tumor necrosis factor alpha—have been measured in isolated placental trophoblastic cells in HIV‐infected and non‐infected pregnant women in an attempt to explore this hypothesis. These inflammatory cytokines and their messenger RNAs were significantly elevated before and after stimulation in HIV‐infected women, supporting the belief that HIV‐infected women present their fetuses a milieu of imbalanced immune factors capable of contributing to immunological rejection. In addition, these elevated inflammatory cytokine levels may contribute to HIV disease progression in fetuses by virtue of activation of HIV gene transcription factors similar to what has been demonstrated in in vitro systems. We therefore propose that HIV infection in pregnant women produces an altered state of certain soluble immune factors, which in concert with other immune factor abnormalities, such as loss of immune selection in the fetal thymus, predisposes the fetus to advanced HIV infection and possible spontaneous abortion.
Role of immunity in maternal—infant HIV‐1 transmission
Authors: Jansson M. , Orlandi P. , Scarlatti G. , Moschese V. , Romiti ML , Cancrini C. , Mancia L. , Livadiotti S. , Castelli‐Gattinara G. , Rossi P. , Halapi E.
Published: March 2012

Factors influencing human immunodeficiency virus type 1 (HIV‐1) mother‐to‐child transmission include both immunological and virological parameters: higher viral loads have been associated with clinical stage of HIV‐1‐infected individuals as well as higher risk of mother‐to‐child transmission. Furthermore, we have shown that transmitting mothers more frequently harbour HIV‐1 isolates with rapid/high syncytium‐inducing (SI) biological phenotype than non‐transmitting mothers do. Genetically homogeneous virus populations have been found in HIV‐1‐infected children at birth, in contrast to the heterogeneous virus populations often found in their infected mothers. This observation suggests that a few virus variants are transmitted or initially are replicating in the child. By comparing the HIV‐1 gp120 V3 region of sequentially obtained samples from infected children with samples obtained from their mothers at delivery we found, however, that multiple variants of HIV‐1 with different outgrowth kinetics can be transmitted. In addition, we have obtained results indicating an impaired ability of the immune response to adapt to the sequence evolution of HIV‐1 in transmitting mothers, as assessed by measuring serum reactivities to peptides representing selected yet closely related V3 sequences. By analysing the presence of antibodies in maternal serum at delivery, which neutralize autologous isolates as well as other primary virus isolates, we have indications that a protective immunity in HIV‐1 mother‐to‐child transmission might exist. Immunotherapy has been assessed in infected adult individuals by passive immunization with a variety of HIV‐1‐specific antibody products. Data from these studies indicated a differential response to therapy according to the stage of the disease. Active vaccine strategies, including envelope glycoproteins, pursued so far in seronegative adult subjects have shown limitations because broadly neutralizing antibodies, such as can be found in infected individuals, have not been evoked. Further investigations are therefore needed to give support for the potential use of either passive and/or active immunization for the prevention of HIV‐1 mother‐to‐child transmission.
Early spontaneous abortions and fetal thymic abnormalities in maternal‐to‐fetal HIV infection
Authors: Shearer WT , Langston C. , Lewis DE , Pham EL , Hammill HH , Kozinetz CA , Kline MW , Hanson IC , Popek EJ
Published: March 2012

The thymus is thought to play a major role in the immunopathogenesis of human immunodeficiency virus (HIV) infection, particularly in maternal‐to‐fetal HIV transmission. Characteristic lesions of the HIV‐infected thymus include a prominent CD4+ CD8+ T lymphocyte depletion at the corticomedullary junction, the region of the thymus where immune selection occurs. At least threefold excess early spontaneous abortions were noted in a cohort of 124 HIV‐infected pregnant women. In these 13 abortuses a very high rate (54%) of HIV vertical transmission was documented, with the thymus gland particularly affected. It is possible that the thymic insult in HIV‐infected fetuses contributes to immune rejection of the fetus, possibly by an imbalance of maternal and fetal T1‐ and T2‐type cytokines, known to be important in HIV disease progression. We propose, therefore, that the early spontaneous abortions occurring in HIV‐infected pregnant women are due, at least in part, to abnormal immune forces created by HIV infection of the thymus.
Human immunodeficiency virus type 1 infection, clinical trials and ethics in paediatrics
Authors: de Martino M. , Galli L. , Amato A. Guarino , Vierucci A.
Published: March 2012

Children are not little adults and questions regarding their treatment must be directly addressed to children. Phase I and II trials should closely follow those in adults, integrated by separate studies in infants. Phase III trials should be carried out in a parallel fashion, flexible enough to be modifiable according to results from larger studies in adults. On condition that study designs are ethically impeccable and are respectful of the intrinsic social weakness of children, as many children as possible should enter clinical trials to offer wide access to drugs and ensure that questions are addressed as rapidly and efficiently as possible.
Birth outcomes following zidovudine exposure in pregnant women: the Antiretroviral Pregnancy Registry
Authors: White A. , Eldridge R. , Andrews E. ,   Antiretroviral Pregnancy Registry Advisory Committee
Published: March 2012

Potential risk of adverse birth outcomes associated with the use of antiretrovirals in human immunodeficiency virus (HIV)‐infected women during pregnancy must be assessed. Data through June 1995 are reported from the worldwide Antiretroviral Pregnancy Registry on the incidence of structural birth defects following prenatal exposure to zidovudine. Healthcare professionals register pregnant women anonymously. Follow‐up is at time of delivery. Results are reviewed semi‐annually by an advisory committee, which follows the Centers for Disease Control and Prevention (CDC) guidelines for definitions of birth defects. From 1989 through to 30 June, 1995, 198 outcomes involving exposure to zidovudine were reported. Of 73 first‐trimester exposures, outcomes included one infant with a birth defect. Of 125 exposures in the second and third trimesters, six infants were reported with birth defects. Data on other antiretrovirals are insufficient for analysis. The Registry findings to date do not show an increase in the number of birth defects (1/63 in the first trimester, or 1.59%, 95% CI 0.083%, 9.69%) following prenatal zidovudine exposure when compared with that expected in the general population; however, the number of outcomes to date represents a sample of insufficient size for developing precise estimates regarding the teratogenic risk of zidovudine.
Gene regulation in the formation of the central nervous system
Authors: Lendahl U.
Published: March 2012

In this review recent advances in our understanding of the genetic control of central nervous system development will be discussed. Stem and/or progenitor cells in the neuroepithelium of the neural tube differentiate into neurons and glial cells in the brain and spinal cord. There is an emerging picture of how key regulatory genes act to control various steps in this differentiation pathway, including organization along the anterio‐posterior and dorso‐ventral body axes. Examples from our own research on nestin and Notch genes will also be presented. It is our hope that information about the biology of these genes may shed light on the nature of the central nervous system stem cell and its developmental decisions.
Synaptogenesis, heterochrony and epigenesis in the mammalian neocortex
Authors: Bourgeois JP
Published: March 2012

In the neocortex of the macaque monkey we have identified and described quantitatively five different phases of synaptogenesis and related them to its functional maturation. In all the cortical areas observed so far, the most rapid phase of synaptogenesis occurs within a time‐window of only 40 days, centred on birth. The modifiability of phase 3 has been tested by bilaterally equilibrated stimulation or deprivation, using experimentally obtained preterm or blind monkeys. Our developmental and experimental observations, as well as phylogenetic comparisons, strongly suggest that the timing and rate of production of synapses during phase 3 are determined by mechanisms that are both intrinsic and common to the whole cortical mantle but can be modified epigenetically later on.
Hormones as regulators of brain development: life‐long effects related to health and disease
Authors: McEwen BS
Published: March 2012

The life‐long interplay between genes and the environment is instrumental in shaping the structure and function of the body, and these interactions apply to the brain as a plastic and ever‐changing organ of the body. Hormones are key regulators of gene expression throughout the body, and the actions of hormones on the brain are instrumental in shaping sex differences and in determining the effects of stress on brain function, including the rate of brain aging. This article also introduces a new term, allostatic load, to describe the cost of adaptation to stressors. Allostasis (stability through change) refers to the output of hormones and autonomic regulators that help to maintain homeostasis, and allostatic load is the consequence of the overactivity of these systems when they are not shut off properly or are forced to be hyperactive by stressors. Key brain areas like the hippocampus are vital to the processing of information that affects how each individual adapts to and responds to potentially stressful life events, and the response of the brain through its control of endocrine and autonomic function in turn determines the degree of allostatic load that an individual will experience. This allostatic load in turn works with the intrinsic genetic susceptibility to determine the progression toward declining health.
Fetal growth retardation: underlying endocrine mechanisms and postnatal consequences
Authors: Gluckman PD , Harding JE
Published: March 2012

Considerable advance has been made in our understanding of the regulation of fetal growth and of the pathophysiology of intrauterine growth retardation. The dominant determinant of fetal growth is nutrient delivery to the conceptus, and the insulin‐like growth factors (IGFs) appear to play a central role in modulating the fetal growth response to the nutritional environment. It has also become clear that events early in gestation, or prior to conception, can be reflected in altered fetal growth and metabolism later in gestation. Intrauterine growth retardation (IUGR) may be due to identifiable genetic or toxic factors or to disordered nutrient delivery. The latter category of IUGR provides the greatest clinical concern with a high incidence of perinatal morbidity and mortality. More recently, epidemiological evidence supported by limited, but growing, experimental data suggest that the postnatal consequences of disturbed fetal growth may include metabolic disease (diabetes mellitus) and cardiovascular disease. This brief review discusses these advances with reference to data from our laboratory.
Changing trend in perinatal management and outcome of extremely low birthweight (ELBW) infants
Authors: Svenningsen NW , Björklund L. , Lindroth M.
Published: March 2012

Perinatal care of the extremely preterm and low birthweight (ELBW) infant is founded on basic principles of physiology and knowledge about the prevailing pathophysiological mechanisms. New therapies in clinical care are usually introduced non‐uniformly, so more often there is a gradual rather than a sudden change in the development of perinatal care, conceivably involving also an important learning process. This was confirmed in an evaluation of respiratory care for ELBW infants (n = 325) over a 9‐year period (1986–1994). Although birthweight (mean 815 g) and degree of immaturity at birth (mean 26.7 weeks of gestation) did not change over the years, our trend analysis showed that the survival rate increased from 47% to 70% (p < 0.04) and the percentage of survivors without bronchopulmonary dysplasia and/or major intracranial haemorrhages (ICH grades 3 and 4) increased from 67% to 87% (p < 0.006). We suggest that besides medical treatment per se, refinement and tuning of nursing and medical care procedures will also affect the total outcome of ELBW infants.
Prenatal determinants of motor disorders
Authors: Stanley FJ
Published: March 2012

Cerebral palsies (CP) are the commonest childhood motor disorders, originating in early childhood as a result of interference in the developing brain. Identifying prenatal factors in CP is a challenge because there is a considerable period of time (years) between the causal event(s) and diagnosis. Four fascinating “natural” situations provided a unique opportunity to identify and measure prenatal exposures in relation to motor disorders, thus establishing the unequivocal role of some factors. However, the majority of studies determining adverse reproductive effects of environmental factors require a retrospective case‐control approach, which present considerable problems. Studies based on the Western Australian CP register suggest that prenatal factors singly or in complex sequences are more common as causes than those occurring perinatally or postnatally. In future, better diagnosis of motor disorders, use of sophisticated scientific techniques to identify markers of neuronal development and the accurate linkage of these findings to clinical patterns of motor dysfunction are required.
Neuropharmacological assessment of growth hormone secretion
Authors: Carro E. , Señaris R. , Peino R. , Leal‐Cerro A. , Popovic V. , Micic D. , Dieguez C. , Casanueva FF
Published: March 2012

The biochemical diagnosis of individuals who are either deficient in growth hormone (GH) or who have alterations in the normal pattern of GH secretion is difficult. The uncertainty surrounding diagnosis reflects the lack of a thorough understanding of the physiology of GH secretion and of the hypothalamic hormones involved. At least three hormones are implicated: GH‐releasing hormone (GHRH), somatostatin and the endogenous ligand of the GH secretagogue receptor, although the role that each plays in the release of GH is not clear from the available experimental evidence. In such a situation, most of the dynamic tests of GH secretory capacity in humans need to undergo a ‘trial and error’ process before being validated. The search for the ‘gold standard’ test of GH secretion is ongoing, and the combination of GHRH plus GH secretagogues will probably play an important role in future clinical diagnosis. □ Growth hormone‐releasing hormone, somatostatin, growth hormone secretagogue, growth hormone‐releasing peptide‐6
An endocrinologist's approach to the growth hormone—insulin‐like growth factor axis
Authors: Rosenfeld RG
Published: March 2012

Gene knockout studies in mice, and a recent case report, have demonstrated that insulin‐like growth factors (IGFs) are major mediators of pre‐ and postnatal growth, whereas the growth‐promoting role of growth hormone (GH) appears to be confined largely to the postnatal period. The IGF axis is now known to consist of the growth factors themselves and at least seven, and probably ten, IGF‐binding proteins. These act either by regulating the availability of IGFs to their receptors, or directly on their target cells. Because of the difficulties associated with GH provocative testing, the central role of IGFs in pre‐ and postnatal growth, and the ease of assaying the various components of the IGF axis, it is suggested that the differential diagnosis of short stature should be based on the concept of IGF deficiency rather than on GH secretory status. □ Growth hormone, insulin‐like growth factor, insulin‐like growth factor‐binding proteins, insulin‐like growth factor receptor, diagnosis
Genes regulating hypothalamic and pituitary development
Authors: Parks JS , Adess ME , Brown MR
Published: March 2012

Several pituitary transcription factors have been identified in the last 3 years. They offer new insights into the processes that direct organogenesis, cell commitment, proliferation and differentiated function. All are DNA‐binding proteins, but they have ties to different families of homeodomain proteins. They differ in their distribution and in the timing of their appearance and extinction. The Rathke's pouch homeobox protein (Rpx) has a paired‐like homeodomain. In mice, it appears on embryonic day 8.5 (day e8.5) and is gone by day e14.5. Its targets for activation are unknown. Pituitary OTX has a tryptophan—phenylalanine—lysine motif in its homeodomain. It appears early and persists. It shows independent activation of the α‐glycoprotein subunit (α‐GSU) and pro‐opiomelanocortin genes and co‐operates with Pit‐1 in activation of the growth hormone and prolactin genes. Pituitary Lim (P‐Lim) protein also acts independently on the α‐GSU gene, and acts in concert with Pit‐1 to activate other genes. A fourth protein, termed the ‘Prophet of Pit‐1’, or Prop‐1, is the recently discovered cause of Ames dwarfism in mice. This paired‐like protein is necessary for the subsequent expression of Pit‐1 in somatotrophs, lactotrophs and thyrotrophs. Any or all of the newly discovered pituitary genes are candidates for mutations causing hypopituitarism in humans. As several are expressed transiently in tissues other than the pituitary during organogenesis, the phenotypes produced by mutations in these genes may prove to be complex. □ Pituitary, transcription, organogenesis, homeobox, homeodomain, mutations, somatotrophs, lactotrophs, thyrotrophs, RPX, P‐OTX, P‐Lim, Prop‐1, Pit‐1
A molecular approach to sex determination in mammals
Authors: Swain A. , Lovell‐Badge R.
Published: March 2012

Mammalian sex determination occurs in the gonad of the developing embryo. This process is dependent on the Y‐chromosome‐encoded Sry gene that acts in the somatic cells of the genital ridge. The transient nature of Sry gene expression suggests that it acts as a switch from one cell fate to another. One of the roles of Sry is to initiate the differentiation of Sertoli cells, which are the first cell type of the testis to be formed. Two genes are thought to be important in Sertoli cell differentiation and function, Sox9, an Sry‐related gene, and SF‐1, a nuclear hormone receptor. Sox9 is expressed in Sertoli cells throughout development of the mouse embryo, and inactivating mutations in this gene in humans give rise to XY females. SF‐1 is also expressed in Sertoli cells and is thought to activate the AMH gene – an early marker of these cells. DAX‐1, an X‐linked member of the nuclear hormone superfamily, is a candidate for a human condition in which duplication of regions of the X chromosome results in XY females. Expression of this gene during mouse development is associated with ovary development and is down‐regulated in the differentiating testis. Mutations in DAX‐1 in humans have shown that this gene is not necessary for testis development. The properties of the DAX‐1 gene suggest that it is important in ovary determination and might therefore be antagonistic to the action of the Sry gene. □ Sex determination, Sry gene, Sox9 gene, SF‐1 gene, AMH gene, DAX‐1 gene, ovary, testis
Effect of 6 months of growth hormone treatment in young children with Prader—Willi syndrome
Authors: Eiholzer U. , Weber R. , Stutz K. , Steinert H.
Published: March 2012

Nine prepubertal children with Prader—Willi syndrome were treated with growth hormone (GH; 24 IU/m2/week) for 6 months. Mean height increased by 0.8 SD and mean weight for height decreased by 0.7 SD over this 6‐month treatment period. Body fat, measured by dual‐energy X‐ray absorptiometry, decreased by 22.5% over the period of GH treatment, whereas fat‐free mass increased by 14%. These preliminary results indicate that GH is effective in increasing height and normalizing body composition in patients with Prader—Willi syndrome. □ Body composition, growth hormone treatment, Prader—Willi syndrome, growth
Effects of growth hormone and insulin‐like growth factor I on T‐ and B‐lymphocytes and immune function
Authors: Geffner M.
Published: March 2012

The concept of a neuro—endocrine—immune axis was proposed more than 50 years ago. Growth hormone (GH), a central component of this axis, has many functions at both a molecular and cellular level, including thymocyte proliferation, stimulation of the cytotoxic activity of natural killer cells and induction of lymphocyte proliferation. Binding of GH to its receptors on lymphocytes stimulates the production of insulin‐like growth factor I (IGF‐I), which mediates the effects of GH on cell proliferation. Other effects of GH on the immune system appear to be direct, such as priming monocytes for enhanced production of hydrogen peroxide in response to phorbol esters, and stimulating neutrophils to secrete superoxide anions associated with enhanced phagocytic activity. Many of the effects of GH are shared by IGF‐I. Despite these observations, and the fact that GH is produced and secreted in immunological tissues such as the thymus and spleen, immune deficiency is not characteristic of GH deficiency in humans. The question remains as to whether GH and IGF‐I could be used as immunotherapy. Currently, both agents have been used in adults to diminish wasting due to acquired immunodeficiency syndrome, and GH has been shown to stimulate CD8+ cell counts. However, they had little impact on CD4+ cell counts, which may be due to IGF‐I and GH resistance in these individuals. The use of GH and IGF‐I as immunotherapies merits further study. □ Growth hormone, insulin‐like growth factor, immune system, lymphocytes
Effects of growth hormone and insulin‐like growth factor I binding to natural killer cells
Authors: Bidlingmaier M. , Auernhammer CJ , Feldmeier H. , Strasburger CJ
Published: March 2012

Human growth hormone (GH) and insulin‐like growth factor I (IGF‐I) are known to bind to, and exert modulatory effects on, different immunocompetent cells, including CD16+/CD3– natural killer (NK) cells. NK cells are involved in various non‐major‐histocompatibility‐complex‐restricted actions of the immune system. Although no clinically significant defect in tumour or virus defence has been reported in GH‐deficient patients, the data available indicate decreased NK cell activity in these patients. In most studies, the absolute number and percentage of NK cells have been found to be normal. Substitution with GH has been reported to normalize the decreased NK cell activity in GH‐deficient patients. In a cross‐sectional study in GH‐deficient adults, decreased basal and interferon‐β (IFN‐β)‐stimulated NK cell activity was observed. In addition, IGF‐I was found to enhance basal and IFN‐β‐stimulated NK cell activity in vitro. Preliminary data on GH binding to NK cells indicate enhanced binding in GH‐deficient patients when compared with normal controls. □ Growth hormone deficiency, human growth hormone, insulin‐like growth factor I, natural killer cell activity
The development of ‘impervious peptides’ as growth hormone secretagogues
Authors: Deghenghi R.
Published: March 2012

The discovery and development of growth hormone (GH) secretagogues is briefly reviewed. GH‐releasing peptide‐6 (GHRP‐6) was the first GHRP to be developed that was active in vivo. Smaller peptides were found to have no GH‐releasing activity in vivo, even though they were potent releasers of GH in vitro. Substituting Trp with 2‐Me‐Trp led to the development of orally active hexarelin and other, smaller, peptides. Although they showed oral activity, absorption rarely exceeded 1% of the administered dose. Nonpeptide GH secretagogues have now been developed that combine reasonable oral absorption with high potency. The next development will be to produce GH secretagogues that overcome the lack of specificity shown by the present molecules. □ Growth hormone secretagogues, growth hormone‐releasing peptide, hexarelin
Growth hormone secretagogues in pathological states: diagnostic implications
Authors: Popovic V. , Micic D. , Damjanovic S. , Obradovic S. , Djurovic M. , Petakov M. , Grudic D. , Golubicic I. , Nikitovic M. , Mitrovic N. , Dieguez C. , Casanueva FF
Published: March 2012

The identification and cloning of the receptor for synthetic growth hormone (GH) secretagogues, even before the endogenous ligand has been identified or its precise physiological role established, suggests that there is a novel target of action for this class of drug. In an attempt to select patients who will benefit from GH treatment, GH secretagogues are being evaluated for their usefulness in diagnosing GH deficiency. The effects of GH‐releasing peptides (GHRPs) on GH release as a function of age and metabolic status, and in different neuroendocrine pathologies, are described, as are the different mechanisms of action, potency and reproducibility of the response to GHRPs compared with GH‐releasing hormone (GHRH). GHRPs offer the advantage over GHRH in natural models of deranged GH secretion in that, in various metabolic states (e.g. obesity, anorexia nervosa and non‐insulin‐dependent diabetes mellitus), the GH response to GHRH is more impaired than it is to GHRPs. However, in some neuroendocrine pathologies, the reverse is true. Thus, both secretagogues provide separate information on the physiological status of somatotrophs. □ Growth hormone‐releasing peptide‐6, growth hormone‐releasing hormone, hexarelin, metabolic derangements, neuroendocrine pathologies
Population‐specific reference values for bone age
Authors: Murata M.
Published: March 2012

Contemporary reference values for assessing skeletal maturity have been obtained for the Japanese population. These were used to compare skeletal maturation with populations from the UK, Belgium, North India and South China. Japanese children were found to attain skeletal maturity, based on measurements of the radius, ulna and short bones of the left hand and wrist, 1 or 2 years earlier than present‐day European and Chinese children. A relative lack of data for the North Indian population made comparison impossible. □ Bone age, skeletal maturation, reference values
Clinical usefulness of bone age determination in the management of tall stature
Authors: Drayer NM
Published: March 2012

Measurements of skeletal maturation are used in the study and management of growth and growth disorders because of the correlation between the degree of skeletal maturation and the potential for further growth. In a study of 147 tall girls, final height was overpredicted by 0.7 ± 2.5 cm (mean ± SD) when based on the Bayley—Pinneau method. The radius—ulna—short bones (Tanner—Whitehouse 2) mark II method of assessment produced an underprediction of final height by 0.8 ± 2.9 cm and 1.0 ± 2.8 cm when the rating was performed by a skilled human or by a computer‐aided system, respectively. These errors in prediction were considered acceptable, although when predictions were made on five girls below 11 years of age, they were less accurate. □ Skeletal maturation, growth disorders, bone age, height prediction, tall girls
Conditions spanning paediatric and adult endocrine practice—the adult perspective
Authors: Monson JP
Published: March 2012

Close liaison between paediatric and adult endocrinologists is essential for optimum care in a variety of clinical conditions. The increasingly recognized importance of growth hormone deficiency (GHD) in the adult is a further indication for maintaining long‐term follow‐up of patients with isolated GHD, which remains demonstrable when linear growth is complete, in addition to those patients presenting in childhood with evidence of structural pituitary disease and anterior pituitary failure. Additional areas in which liaison is desirable include congenital adrenal hyperplasia, precocious puberty, gonadal dysgenesis and other disorders of primary and secondary sexual development, thyroid dysfunction, diabetes mellitus, inherited neoplasia syndromes and those conditions, for example Cushing's syndrome, which present in childhood but are more common in adult clinical endocrine practice. In this brief review, the diagnostic spectrum of the paediatric/adult interface is described and the rationale for an integrated approach to treatment and follow‐up is outlined. □ Paediatric endocrinology, adult endocrinology, growth hormone deficiency, gonadal dysfunction, congenital adrenal hyperplasia, diabetes mellitus, thyroid dysfunction, inherited neoplasia syndromes, Cushing's syndrome
Endocrine and nutritional regulation of prenatal growth
Authors: Gluckman PD
Published: March 2012

Fetal growth in late gestation is primarily determined by the functional status of the pathways by which nutrients are transferred from the maternal compartment, across the placenta, and taken up by the fetal tissues. Both the maternal and fetal endocrine systems can influence this pathway at several levels, including regulation of placental metabolism. The primary fetal axis involved in the regulation of fetal growth is the glucose—insulin—insulin‐like growth factor I axis. □ Fetus, intrauterine growth retardation, insulin‐like growth factor I, growth hormone
Early influences on embryonic and placental growth
Authors: Robinson JS , Hartwich KM , Walker SK , Erwich JJHM , Owens JA
Published: March 2012

Growth of the placenta is influenced by events before and during early pregnancy. Some of these events set the growth trajectory of the placenta and the fetus for the remainder of the pregnancy. Maternal size and nutrition, and the local metabolic, cytokine and hormonal environment of the embryo all affect growth of the placenta. □ Placental growth, embryo development, maternal size, maternal nutrition, dietary intake
Aetiology, morphology and body composition of infants born small for gestational age
Authors: Lapillonne A. , Peretti N. , Ho PS , Claris O. , Salle BL
Published: March 2012

Infants born small for gestational age (SGA) are a heterogeneous group. Both the timing and duration of the intrauterine insult determine the physical condition and body composition of the infant at birth. Infants with symmetrical intrauterine growth retardation (IUGR) have a similar body composition at birth to weight‐matched infants born appropriate for gestational age. However, these infants are more likely to remain shorter and lighter than normal infants. In contrast, infants with asymmetrical IUGR have reduced fat deposition but are more likely to exhibit catch‐up growth during the first few months of life. The low mortality and morbidity rates in infants born SGA observed in recent studies are linked to their appropriate perinatal management, including adequate early nutritional support. □ Body composition, dual‐energy X‐ray absorptiometry, aetiology, neonate, preterm, small for gestational age
Metabolic consequences of intrauterine growth retardation
Authors: Hales CN
Published: March 2012

Epidemiological studies have revealed strong and reproducible links between indices of poor fetal, and possibly infant, growth and susceptibility to the development of glucose intolerance and insulin resistance syndrome in adult life. The ‘thrifty phenotype’ hypothesis has been proposed to explain these associations. Key features of the hypothesis are: (i) intrauterine growth retardation has a nutritional basis and the resulting altered fetal environment permanently alters the development and metabolic functions of organs; (ii) these alterations are beneficial to survival in a poor nutritional environment, but may lead to diseases such as non‐insulin‐dependent diabetes mellitus if nutrition is abundant and obesity occurs in adult life. Tests of this hypothesis in an animal model in which pregnant and/or lactating rats were fed a diet with a reduced protein content have shown that liver metabolism in the offspring is permanently altered despite their being weaned onto a normal diet. The longevity of male offspring may be significantly increased or decreased depending on whether growth retardation is restricted to the period of suckling or pregnancy, respectively. The latter finding raises questions about potentially detrimental effects of ‘catch‐up’ growth. □ Intrauterine growth retardation, fetal growth, catch‐up growth, ‘thrifty phenotype’ hypothesis, non‐insulin‐dependent diabetes mellitus, animal model
Nutritional management and growth hormone treatment of preterm infants born small for gestational age
Authors: Lafeber HN
Published: March 2012

In severe cases of intrauterine growth retardation, elective preterm delivery may provide the possibility for nutritional intervention to prevent some of the long‐term consequences of the catabolic condition in utero. Neonatal nutritional management is aimed at providing a high protein intake of up to 4 g/kg/day in order to obtain the rapid increase in protein that is seen in normally growing infants during the early postnatal period. Unfortunately, due to impaired production of urea, high plasma levels of ammonia, which may be rate limiting with respect to an optimal gain in protein, are often observed in the preterm infant born small for gestational age (SGA). In an attempt to stimulate protein synthesis in preterm infants born SGA, growth hormone (GH) treatment was given to seven such infants during the early postnatal period. The infants received daily subcutaneous injections of GH (1.0 IU/kg/day) from postnatal day 7 until a body weight of 2000 g was reached (postnatal week 7–8). A further seven preterm infants born SGA were studied as controls. GH treatment had no significant effects on growth, body composition, net protein gain and glucose metabolism. Furthermore, plasma levels of insulin‐like growth factor I (IGF‐I) and IGF‐binding protein‐3 revealed a normal developmental increase and were not significantly altered by GH treatment. These results may be explained by a relative GH insensitivity or resistance during this period of early preterm life. □ Growth hormone, small for gestational age, intrauterine growth retardation, preterm infant, protein metabolism, glucose metabolism, insulin‐like growth factor I, insulin‐like growth factor‐binding protein‐3
Education of Children Left Behind in Rural China
Authors: Lu Yao
Published: March 2012

Despite China's substantial internal migration, long‐standing rural–urban bifurcation has prompted many migrants to leave their children behind in rural areas. This study examined the consequences of out‐migration for children's education using longitudinal data from the China Health and Nutrition Survey (N = 885). This study took into account the complex family migration strategies and distinguished various types of migration in China, including different forms of parental migration as well as sibling migration. The results showed that migration of siblings generates benefits for children's education, which is particularly pronounced for girls and children at middle‐school levels. But parental migration has not given children left behind a significant advantage in educational prospects as their parents had hoped. Younger children seem to be especially susceptible to the disruptive effect of parental out‐migration.
Older Parents Providing Child Care for Adult Children: Does It Pay Off?
Authors: Geurts Teun , Poortman Anne‐Rigt , van Tilburg Theo G.
Published: March 2012

This study examined whether past grandparental child care is related to present support from adult children. On the basis of social exchange theory, the authors expected that grandparental child care creates a debt that is repaid in the form of receiving support later in life. Using data from the Longitudinal Aging Study Amsterdam (N = 349 parents, N = 812 adult children), the authors found that grandparents who frequently provided child care for sons in the past more often received instrumental and emotional support from these sons approximately 13 years later than grandparents who less frequently provided child care. Investments in daughters did not pay off. Instrumental support other than child‐care provision did not predict receiving support from either sons or daughters, but emotional support did. These results support the notion of long‐term reciprocity in parent–child relationships, but its importance depends on the child's gender and the type of earlier investment.
Single Mothers' Religious Participation and Early Childhood Behavior
Authors: Petts Richard J.
Published: March 2012

Using data on 1,134 single mothers from the Fragile Families and Child Wellbeing Study, this study examined trajectories of religious participation among single mothers and whether these trajectories were associated with early childhood behavior. The results suggested that single mothers experienced diverse patterns of religious participation throughout their child's early life; some mothers maintained a consistent pattern of religious participation (or nonparticipation), and other mothers increased their participation. The results also suggested that religious participation was associated with greater involvement with children, reduced parenting stress, and a lower likelihood of engaging in corporal punishment. Young children raised by mothers who frequently attended religious services were less likely to display problem behaviors, and this relationship was partially mediated by increased child involvement, lower stress, and less frequent corporal punishment. Overall, religious participation may provide resources for single mothers that encourage them to engage in parenting practices that promote positive child development.
Understanding Unique Effects of Parental Incarceration on Children: Challenges, Progress, and Recommendations
Authors: Johnson Elizabeth I. , Easterling Beth
Published: March 2012

Growth in U.S. incarceration rates during the 1980s and 1990s prompted a body of research focused on understanding the diverse effects of incarceration on individuals, families, and communities. An area of particular interest has been how the incarceration of a parent may affect child well‐being. Despite what appears to be converging evidence that parental incarceration poses a significant threat to child development, this area of inquiry has yet to overcome important methodological and conceptual challenges related to selection bias. It is therefore unclear whether the difficulties that have been observed among children whose parents are incarcerated are due to the incarceration itself or to other adversities that children have experienced. The purpose of this article is to draw attention to these issues, to summarize empirical and conceptual progress in overcoming these challenges, and to suggest directions for future research.
Oxidative Stress in the in vivo DMBA Rat Model of Breast Cancer: Suppression by a Voltage‐gated Sodium Channel Inhibitor (RS100642)
Authors: Batcioglu Kadir , Uyumlu A. Burcin , Satilmis Basri , Yildirim Battal , Yucel Neslihan , Demirtas Hakan , Onkal Rustem , Guzel R. Mine , Djamgoz Mustafa B. A.
Published: March 2012

Breast cancer (BCa) was induced in vivo in female rats with 7,12‐dimethylbenz(a)anthracene (DMBA). Two main questions were addressed. Firstly, would the carcinogenesis be accompanied by oxidative stress as signalled by superoxide dismutase, glutathione peroxidase, malondialdehyde and total nitrate? Secondly, would treating the rats additionally with a blocker of voltage‐gated sodium channel (VGSC) activity, shown previously to promote BCa progression, affect the oxidative responses? The DMBA‐induced increases in the antioxidant systems were completely blocked by the VGSC inhibitor RS100642, which also significantly prolonged the lifespan. We conclude that VGSC inhibition in vivo can significantly protect against oxidative stress and improve survival from tumour burden.
The CB1 Receptor Antagonist, AM281, Improves Recognition Loss Induced by Naloxone in Morphine Withdrawal Mice
Authors: Vaseghi Golnaz , Rabbani Mohammed , Hajhashemi Valiollah
Published: March 2012

Morphine withdrawal leads to the activation of endocannabinoid system and cognitive deficits. The aim of this study was to evaluate the effects of AM281, a cannabinoid antagonist/inverse agonist, on memory deficit following naloxone‐precipitated morphine withdrawal in mice. Male mice were made dependent by increasing doses of morphine (30–90 mg/kg) twice daily for 3 days. The object recognition task was used to evaluate memory dysfunction. The test comprised three sections: habituation for 15 min., first trial for 12 min. and test trial for 5 min. In this learning paradigm, the difference in exploration between a previously seen object and a new object is taken as an index of memory performance (recognition index). The recognition index was assessed on the third day of morphine treatment by the injection of 0.1 mg/kg naloxone 3 hr after the last dose of morphine. Chronic administration of AM281 at 2.5 mg/kg significantly improved the memory impairment, producing a recognition index of 36.0 ± 3.9 as compared with vehicle‐treated data (recognition index = −3.1 ± 8.2%). A single dose of AM281 at 5 mg/kg improved the recognition index from −1.5 ± 3.9% in morphine withdrawal animals to 18.5 ± 11.6%. Concurrent administration of AM281 with morphine proved to be more effective in protecting the animals from losing their memory compared to acute action of AM281. These results indicate that the contribution of the cannabinoid system to memory deficit is attributable to morphine withdrawal. By blocking cannabinoid receptors, AM281 may become useful in preventing memory deficit after morphine withdrawal.