bluuebunny/crossref_metadata_2025 huggingface dataset:
Early-Life Risk Factors for Occurrence of Atopic Dermatitis During the First Year
Authors: Sugiyama Mikio , Arakawa Hirokazu , Ozawa Kiyoshi , Mizuno Takahisa , Mochizuki Hiroyuki , Tokuyama Kenichi , Morikawa Akihiro
Published: March 2007

OBJECTIVE. In a prospective birth cohort study, we sought to identify perinatal predictors of the occurrence of atopic dermatitis in the first year of life.

METHODS. Associations of family history, infection during pregnancy, cord blood cytokine concentrations, and skin function parameters with atopic dermatitis were analyzed. Stratum corneum hydration was measured with an impedance meter until 5 days after delivery and again at 1 month.

RESULTS. Complete data were obtained for 213 infants, including 27 diagnosed by a physician as having atopic dermatitis during their first year and 26 diagnosed as having infantile eczema during their first month. The risk of atopic dermatitis during the first year of life was related to maternal atopic dermatitis, lower concentrations of macrophage inflammatory protein-1β in cord blood, and greater skin moisture in the surface and stratum corneum of the forehead and cheek at 1 month of age but not to viral or bacterial infection during pregnancy or breastfeeding. Paternal hay fever was associated negatively with the development of atopic dermatitis. High concentrations of interleukin-5, interleukin-17, and macrophage chemotactic protein-1 and only surface moisture in the cheek were associated with greater risk of infantile eczema in the first month.

CONCLUSIONS. The association of atopic dermatitis in infancy with reduced neonatal macrophage inflammatory protein-1β levels suggests a link with immature immune responses at birth. Stratum corneum barrier disruption in atopic dermatitis may involve impairment of cutaneous adaptation to extrauterine life. The majority of risk factors had different effects on infant eczema and atopic dermatitis, indicating different causes.
Influenza Vaccine Coverage and Missed Opportunities Among Inner-city Children Aged 6 to 23 Months: 2000-2005
Authors: Verani Jennifer R. , Irigoyen Matilde , Chen Shaofu , Chimkin Frank
Published: March 2007

OBJECTIVE. In 2002, the Advisory Committee on Immunization Practices recommended universal influenza vaccination of 6- to 23-month-olds. Little is known about coverage and missed opportunities for influenza vaccination at inner-city practices. The objective of this study was to assess the 2000–2001 to 2004–2005 coverage and the prevalence of missed opportunities for influenza vaccination among inner-city children.

METHODS. We conducted a retrospective review for the 2000–2001 to 2004–2005 influenza seasons at a practice network in New York City. The study population included 5 annual cohorts of 6- to 29-month olds as of March 31 of each year with ≥1 visit to the network in the previous 12 months (n = 7063). Immunization data were obtained from the network registry and the New York Citywide Immunization Registry. Coverage levels were estimated for 1 dose (partial) and 2 doses (full). Missed opportunities were assessed for visits within each influenza season.

RESULTS. Coverage rose steadily throughout the 5 years (full: 1.6% to 23.7%; partial: 1.5% to 18.1%). The relationship between year and coverage was linear. Missed opportunities occurred in 82% of visits and were more common for first (89%) than for repeat doses (38%). Missed opportunities per child per season decreased from 2.9 to 2.0 during the study period.

CONCLUSIONS. Influenza vaccine coverage among 6- to 23-month-olds at inner-city practices increased steadily from 2000–2001 through 2004–2005, and the prevalence of missed opportunities per child decreased. However, coverage remained suboptimal, with most of children not vaccinated or undervaccinated. Missed opportunities were major contributors to low coverage.
Twelve-Month Effectiveness of a Parent-led, Family-Focused Weight-Management Program for Prepubertal Children: A Randomized, Controlled Trial
Authors: Golley Rebecca K. , Magarey Anthea M. , Baur Louise A. , Steinbeck Katharine S. , Daniels Lynne A.
Published: March 2007

BACKGROUND. Parenting-skills training may be an effective age-appropriate child behavior-modification strategy to assist parents in addressing childhood overweight.

OBJECTIVE. Our goal was to evaluate the relative effectiveness of parenting-skills training as a key strategy for the treatment of overweight children.

DESIGN. The design consisted of an assessor-blinded, randomized, controlled trial involving 111 (64% female) overweight, prepubertal children 6 to 9 years of age randomly assigned to parenting-skills training plus intensive lifestyle education, parenting-skills training alone, or a 12-month wait-listed control. Height, BMI, and waist-circumference z score and metabolic profile were assessed at baseline, 6 months, and 12 months (intention to treat).

RESULTS. After 12 months, the BMI z score was reduced by ∼10% with parenting-skills training plus intensive lifestyle education versus ∼5% with parenting-skills training alone or wait-listing for intervention. Waist-circumference z score fell over 12 months in both intervention groups but not in the control group. There was a significant gender effect, with greater reduction in BMI and waist-circumference z scores in boys compared with girls.

CONCLUSION. Parenting-skills training combined with promoting a healthy family lifestyle may be an effective approach to weight management in prepubertal children, particularly boys. Future studies should be powered to allow gender subanalysis.
Work-Related Hazards and Workplace Safety of US Adolescents Employed in the Retail and Service Sectors
Authors: Runyan Carol W. , Schulman Michael , Dal Santo Janet , Bowling J. Michael , Agans Robert , Ta Myduc
Published: March 2007

OBJECTIVE. Our goal was to examine the hazard exposures, work experiences, and workplace safety training of adolescents employed in retail and service jobs in the United States.

METHODS. This was a cross-sectional telephone survey among working adolescents, 14 to 18 years old, in the continental United States. Data were collected in 2003. Survey items measured self-reported hazard exposures, training, and supervision experiences of working adolescents.

RESULTS. Teens reported working an average of 16.2 hours per week during the school year, including working an average of 2.9 times per week after 7 pm on school nights and 2.6 nights per week after 9 pm. Thirty-seven percent of those under age 16 reported working after 7 pm on a school night, indicating employer violation of federal law. Teens typically perform multiple kinds of tasks in a given job. Higher proportions of females than males are involved in cash handling (84% vs 61%), whereas males are more likely than females to be involved in physically challenging tasks, such as lifting heavy objects (57% vs 22%) or working at heights (35% vs 17%). Despite federal regulations prohibiting teens under 18 from using certain types of dangerous equipment (eg, slicers, dough mixers, box crushers, paper balers) or serving or selling alcohol in places where it is consumed, 52% of males and 43% of females reported having performed ≥1 prohibited task. Although more males reported receiving safety training, they were also more likely to report working without supervision than their female counterparts.

CONCLUSIONS. Teens are exposed to multiple hazards, use dangerous equipment despite federal prohibitions, and work long hours during the school week. They also lack consistent training and adult supervision on the job. It is important for adolescent medicine practitioners to become involved in prevention efforts through both anticipatory guidance and policy advocacy.
Childhood Bone Mass Acquisition and Peak Bone Mass May Not Be Important Determinants of Bone Mass in Late Adulthood
Authors: Gafni Rachel I. , Baron Jeffrey
Published: March 2007

During childhood and adolescence, bone mass acquisition occurs primarily through skeletal growth. It is widely assumed that bone mass acquisition throughout childhood is an important determinant of the risk of osteoporosis in late adulthood; bone mass is thought to resemble a bank account in which deposits persist indefinitely. However, several well-controlled clinical studies suggest that increasing bone mass acquisition during childhood will have only transient effects. A likely explanation is that bone mass is governed by a homeostatic system that tends to return to a set point after any perturbation and, therefore, bone mass depends primarily on recent conditions, not those in the distant past. Indeed, in an animal model, we have shown evidence that bone mass acquisition in early life has no effect on bone mass in adulthood, in part because many areas of the juvenile skeleton are replaced in toto through skeletal growth. Therefore, it should not be assumed that alterations in childhood bone mass acquisition will affect bone mass many decades later in late adulthood. This issue remains open and the solution may depend on the type of childhood condition (for example calcium intake versus exercise) and its magnitude, timing, and duration. To date, both animal studies and clinical studies suggest that much of the effect of early bone mass acquisition does not persist.
Bone Accrual in Children: Adding Substance to Surfaces
Authors: Rauch Frank
Published: March 2007

The mass of growing bones increases through changes in outer dimensions and through the net addition of tissue on inner bone surfaces. In this overview I examine bone accrual as it occurs on trabecular (inner) and periosteal (outer) surfaces. In the axial skeleton, the amount of trabecular bone increases during development, because trabeculae grow thicker as a result of bone remodeling with a positive balance. Remodeling is a process in which osteoblasts and osteoclasts are tightly linked (“coupled”) in time and space. In contrast to trabecular thickness, trabecular number and material density change little throughout development. Bone accrual on periosteal surfaces leads to an increase in bone size, which is a crucial determinant of bone strength throughout life. Periosteal osteoblasts deposit new bone on an extended surface area and over an extended period of time without being interrupted by osteoclasts. This type of bone metabolic activity is called modeling, which is much more efficient than remodeling for increasing bone mass. In the past, research has focused on bone remodeling on trabecular surfaces. However, the key to an improved understanding of bone mass and strength development in children will lie with studies on bone modeling on periosteal surfaces.
Glucocorticoid-Induced Osteoporosis in Children: Impact of the Underlying Disease
Authors: Leonard Mary B.
Published: March 2007

Glucocorticoids inhibit osteoblasts through multiple mechanisms, which results in significant reductions in bone formation. The growing skeleton may be especially vulnerable to adverse glucocorticoid effects on bone formation, which could possibly compromise trabecular and cortical bone accretion. Although decreased bone mineral density has been described in various pediatric disorders that require glucocorticoids, and a population-based study reported increased fracture risk in children who require >4 courses of glucocorticoids, some of the detrimental bone effects attributed to glucocorticoids may be caused by the underlying inflammatory disease. For example, inflammatory cytokines that are elevated in chronic disease, such as tumor necrosis factor α, suppress bone formation and promote bone resorption through mechanisms similar to glucocorticoid-induced osteoporosis. Summarized in this review are changes in bone density and dimensions during growth, the effects of glucocorticoids and cytokines on bone cells, the potential confounding effects of the underlying inflammatory-disease process, and the challenges in interpreting dual-energy x-ray absorptiometry results in children with altered growth and development in the setting of glucocorticoid therapy. Two recent studies of children treated with chronic glucocorticoids highlight the differences in the effect of underlying disease, as well as the importance of associated alterations in growth and development.
Transmission of West Nile Virus Through Human Breast Milk Seems to Be Rare
Authors: Hinckley Alison F. , O'Leary Daniel R. , Hayes Edward B.
Published: March 2007

INTRODUCTION.In September 2002, possible transmission of West Nile virus via human milk was reported for the first time.

METHODS.Since 2003, the Centers for Disease Control and Prevention collected reports of maternal or infant West Nile virus illness during the breastfeeding period. All of the reported instances were reviewed. In addition, milk samples from women infected during pregnancy were tested for West Nile virus RNA and West Nile virus–specific antibodies.

RESULTS.Six infants were reported to have breastfed from mothers with West Nile virus fever. Five of the 6 infants had no illness or detectable antibodies to West Nile virus in serum after onset of maternal illness. One infant who was not tested and developed a rash was otherwise well 1 week after onset of maternal illness. In addition, 2 infants were reported to have developed West Nile virus illness while breastfeeding; preceding maternal illness was not documented. Two breastfed infants whose mothers acquired West Nile virus fever in the last week of pregnancy developed West Nile virus–specific antibodies; both infant infections could have been congenitally acquired. Of 45 milk samples from women infected with West Nile virus during pregnancy, 2 had West Nile virus RNA, and 14 had immunoglobin M antibodies to West Nile virus.

CONCLUSIONS.Of 10 reported instances since 2003 of maternal or infant West Nile virus illness while breastfeeding, transmission of West Nile virus through human milk could neither be ruled out nor confirmed for 5 cases; in 5 others, serologic tests indicated no vertical transmission. Transmission of West Nile virus through breastfeeding seems to be rare, but more information is needed.
Weight Status in Young Girls and the Onset of Puberty
Authors: Lee Joyce M. , Appugliese Danielle , Kaciroti Niko , Corwyn Robert F. , Bradley Robert H. , Lumeng Julie C.
Published: March 2007

OBJECTIVE. We sought to examine the association between weight status in early childhood and onset of puberty.

PATIENTS AND METHODS. The study included 354 girls from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development. Girls were followed longitudinally with height and weight measurements at 36 and 54 months and grades 1, 4, 5, and 6 and with assessment of pubertal stage by physical examination and maternal report in grades 4 through 6. The main outcome was the presence of early puberty, indexed as follows: (a) breast development at or more than Tanner stage 2 by physical examination at grade 4; (b) breast development at or more than Tanner stage 3 by physical examination at grade 5; (c) maternal report of breast development at or more than Tanner stage 3 at grade 5; and (d) maternal report of menarche having already occurred (yes versus no) at grade 6. Multiple logistic regression models predicting early versus late puberty were constructed by using the covariate BMI z score at 36 months, rate of change of BMI and accelerated BMI between 36 months and grade 1, race, maternal education, and maternal age of menarche.

RESULTS. BMI z score at 36 months, rate of change of BMI between 36 months and grade 1, an earlier age of maternal menarche, and nonwhite race were each consistently and positively associated with an earlier onset of puberty across the various measures of puberty.

CONCLUSIONS. Higher BMI z score in girls as young as 36 months of age and higher rate of change of BMI between 36 months old and grade 1, a period well before the onset of puberty, are associated with earlier puberty, which suggests that increasing rates of obesity in the United States may result in an earlier average age of onset of puberty for US girls.
Is Nephrocalcinosis in Preterm Neonates Harmful for Long-term Blood Pressure and Renal Function?
Authors: Kist-van Holthe Joana E. , van Zwieten Paul H.T. , Schell-Feith Eveline A. , Zonderland Harmien M. , Holscher Herma C. , Wolterbeek Ron , Veen Sylvia , Frolich Marijke , van der Heijden Bert J.
Published: March 2007

OBJECTIVE. The aim of our study was to examine long-term effects of nephrocalcinosis in prematurely born children.

PATIENTS AND METHODS. Preterm neonates (gestational age <32 weeks) with (n = 42) and without (n = 32) nephrocalcinosis were prospectively studied at a mean age of 7.5 (±1.0) years.

RESULTS. Blood pressure did not differ in ex-preterm infants with and without nephrocalcinosis but was significantly higher than expected for healthy children. In comparison to healthy children, more ex-preterm infants with neonatal nephrocalcinosis had (mild) chronic renal insufficiency (glomerular filtration rate: <85 mL/min per 1.73 m2; 6 of 40); this is in contrast to ex-preterm infants without neonatal nephrocalcinosis (2 of 32). Tubular phosphate reabsorption and plasma bicarbonate were significantly lower in children with nephrocalcinosis compared with children without nephrocalcinosis. In addition, more ex-preterm infants with and without nephrocalcinosis than expected had low values for plasma bicarbonate and early-morning urine osmolality compared with healthy children. Kidney length of ex-preterm infants with and without nephrocalcinosis was significantly smaller than expected in healthy children of the same height. Nephrocalcinosis persisted long-term in 4 of 42 children but was not related to blood pressure, kidney length, or renal function.

CONCLUSIONS. Nephrocalcinosis in preterm neonates can have long-term sequelae for glomerular and tubular function. Furthermore, prematurity per se is associated with high blood pressure, relatively small kidneys, and (distal) tubular dysfunction. Long-term follow-up of blood pressure and renal glomerular and tubular function of preterm neonates, especially with neonatal nephrocalcinosis, seems warranted.
Risk of Recurrent Childhood Arterial Ischemic Stroke in a Population-Based Cohort: The Importance of Cerebrovascular Imaging
Authors: Fullerton Heather J. , Wu Yvonne W. , Sidney Stephen , Johnston S. Claiborne
Published: March 2007

OBJECTIVE. Few data exist regarding rates and predictors of recurrence after childhood arterial ischemic stroke. We sought to establish such rates within a large, multiethnic population and determine whether clinical vascular imaging predicts recurrence.

PATIENTS AND METHODS. In a population-based cohort study, we collected data on all documented cases of arterial ischemic stroke among 2.3 million children (<20 years old) enrolled in a northern Californian managed care plan from January 1993 to December 2004. Perinatal strokes were those that occurred by 28 days of life. Data on cerebrovascular imaging (conventional or magnetic resonance angiography), including presence of vascular abnormalities, were abstracted from official radiology reports. We used Kaplan-Meier survival-analysis techniques to determine rates and predictors of recurrent stroke.

RESULTS. Among 181 incident childhood stroke cases (84 perinatal; 97 later childhood), there were 16 recurrent strokes (1 after a perinatal stroke) at a median of 2.7 months. The 5-year cumulative recurrence rates were 1.2% after perinatal stroke and 19% after later childhood stroke. Of the 97 children with later childhood strokes, 52 received cerebrovascular imaging, predominantly magnetic resonance angiography (n = 36) and conventional angiography (n = 26). Although there were no recurrences among children with normal vascular imaging, children with a vascular abnormality had a 5-year cumulative recurrence rate of 66%.

CONCLUSIONS. Strokes recur in one fifth of cases of later childhood arterial ischemic stroke but are rare after perinatal stroke. Among the later childhood cases, cerebrovascular imaging identifies those at highest risk for recurrence.
The Late Effects of Childhood Cancer Therapy
Authors: Dickerman Joseph D.
Published: March 2007

In this article the difficulties that face survivors of childhood cancer therapy are presented, and the late effects of such therapy, separated into nonmalignant and malignant late effects, are discussed according to organ system. Recommendations for monitoring the late effects are set forth. A table listing radiation-therapy site and chemotherapeutic agents and selected late effects that result from their use is provided. Finally, a brief recommendation regarding the establishment of a late-effects clinic is also presented.
High-Deductible Health Plans and the New Risks of Consumer-Driven Health Insurance Products
Authors:   Committee on Child Health Financing
Published: March 2007

Consumer-driven health care is the most noteworthy development in health insurance since the widespread adoption of health maintenance organizations and preferred provider organizations in the 1980s. The most common consumer-driven health plan is the high-deductible health plan, which is essentially a catastrophic health insurance plan, often linked with tax-advantaged spending accounts, with very high deductibles, fewer benefits, and higher cost-sharing than conventional health maintenance organization or preferred provider organization plans. The financial risks are significant under high-deductible health plans, especially for low- to moderate-income families and for families whose children have special health care needs. Of concern for pediatricians are the potential quality risks that are predictable in high-deductible health plans, in which families are likely to delay or avoid seeking care, especially preventive care (if it is not exempted from the deductible), when they are faced with paying for care before the deductible is met. This policy statement provides background information on the most common consumer-driven health plan model, discusses the implications for pediatricians and families, and offers recommendations pertaining to health plan product design, education, practice administration, and research.
Optimized Flow Cytometric Analysis of Central Nervous System Tissue Reveals Novel Functional Relationships Among Cells Expressing CD133, CD15, and CD24
Authors: Panchision David M. , Chen Hui-Ling , Pistollato Francesca , Papini Daniela , Ni Hsiao-Tzu , Hawley Teresa S.
Published: March 2007

Although flow cytometry is useful for studying neural lineage relationships, the method of dissociation can potentially bias cell analysis. We compared dissociation methods on viability and antigen recognition of mouse central nervous system (CNS) tissue and human CNS tumor tissue. Although nonenzymatic dissociation yielded poor viability, papain, purified trypsin replacement (TrypLE), and two purified collagenase/neutral protease cocktails (Liberase-1 or Accutase) each efficiently dissociated fetal tissue and postnatal tissue. Mouse cells dissociated with Liberase-1 were titrated with antibodies identifying distinct CNS precursor subtypes, including CD133, CD15, CD24, A2B5, and PSA-NCAM. Of the enzymes tested, papain most aggressively reduced antigenicity for mouse and human CD24. On human CNS tumor cells, CD133 expression remained highest after Liberase-1 and was lowest after papain or Accutase treatment; Liberase-1 digestion allowed magnetic sorting for CD133 without the need for an antigen re-expression recovery period. We conclude that Liberase-1 and TrypLE provide the best balance of dissociation efficiency, viability, and antigen retention. One implication of this comparison was confirmed by dissociating E13.5 mouse cortical cells and performing prospective isolation and clonal analysis on the basis of CD133/CD24 or CD15/CD24 expression. Highest fetal expression of CD133 or CD15 occurred in a CD24hi population that was enriched in neuronal progenitors. Multipotent cells expressed CD133 and CD15 at lower levels than did these neuronal progenitors. We conclude that CD133 and CD15 can be used similarly as selectable markers, but CD24 coexpression helps to distinguish fetal mouse multipotent stem cells from neuronal progenitors and postmitotic neurons. This particular discrimination is not possible after papain treatment.

Disclosure of potential conflicts of interest is found at the end of this article.
Spontaneous Transformation of Human Adult Nontumorigenic Stem Cells to Cancer Stem Cells Is Driven by Genomic Instability in a Human Model of Glioblastoma
Authors: Shiras Anjali , Chettiar Sivarajan T , Shepal Varsha , Rajendran Ganeshkumar , Prasad G. Rajendra , Shastry Padma
Published: March 2007

The presence of a CD133+/nestin+ population in brain tumors suggests that a normal neural stem cell may be the cell of origin for gliomas. We have identified human CD133-positive NSCs from adult glioma tissue and established them as long-term in vitro cultures human neuroglial culture (HNGC)-1. Replicative senescence in HNGC-1 led to a high level of genomic instability and emergence of a spontaneously immortalized clone that developed into cell line HNGC-2 with features of cancer stem cells (CSCs), which include the ability for self-renewal and the capacity to form CD133-positive neurospheres and develop intracranial tumors. The data from our study specify an important role of genomic instability in initiation of transformed state as well as its progression into highly tumorigenic CSCs. The activated forms of Notch and Hes isoforms were expressed in both non-neoplastic neural stem cells and brain tumor stem cells derived from it. Importantly, a significant overexpression of these molecules was found in the brain tumor stem cells. These findings suggest that this model comprised of HNGC-1 and HNGC-2 cells would be a useful system for studying pathways involved in self-renewal of stem cells and their transformation to cancer stem cells.

Disclosure of potential conflicts of interest is found at the end of this article.
A Rho-kinase inhibitor, fasudil, prevents development of diabetes and nephropathy in insulin-resistant diabetic rats
Authors: Kikuchi Yuichi , Yamada Muneharu , Imakiire Toshihiko , Kushiyama Taketoshi , Higashi Keishi , Hyodo Naomi , Yamamoto Kojiro , Oda Takashi , Suzuki Shigenobu , Miura Soichiro
Published: March 2007

Fasudil, a Rho-kinase inhibitor, may improve insulin signaling. However, its long-term effect on metabolic abnormalities and its preventive effect on diabetic nephropathy are still unknown. We assessed these effects of fasudil in insulin-resistant diabetic rats, comparing them with those of an angiotensin II receptor blocker, olmesartan. Male Otsuka Long–Evans Tokushima fatty (OLETF) and Long–Evans Tokushima Otsuka, non-diabetic control, rats at 15 weeks of age were used. OLETF rats were randomized to receive a low or a high dose of fasudil or olmesartan for 25 weeks. To examine the therapeutic effects after the development of diabetes, OLETF rats at 30 weeks of age were given fasudil for 10 weeks. Administration of high-dose fasudil completely suppressed the development of diabetes, obesity, and dyslipidemia and increased serum adiponectin levels in OLETF rats. High-dose olmesartan also decreased hemoglobin A1c and increased serum adiponectin. There was a significant correlation between hemoglobin A1c and serum adiponectin or free fatty acid levels. The treatment with high-dose fasudil ameliorated proteinuria, glomerulosclerosis, renal interstitial fibrosis, and macrophage infiltration in OLETF rats. Olmesartan, even at the low dose, suppressed renal complications. The treatment with fasudil after the development of diabetes improved the metabolic abnormalities in OLETF rats, but could not suppress the progression of nephropathy. We conclude that the long-term treatment with fasudil prevents the development of diabetes, at least in part, by improving adipocyte differentiation in insulin-resistant diabetic rats. Early use of fasudil may prevent diabetic nephropathy.
Amino acids, taste circuits, and feeding behavior in Drosophila: towards understanding the psychology of feeding in flies and man
Authors: Melcher Christoph , Bader Ruediger , Pankratz Michael J
Published: March 2007

Feeding can be regulated by a variety of external sensory stimuli such as olfaction and gustation, as well as by systemic internal signals of feeding status and metabolic needs. Faced with a major health epidemic in eating-related conditions, such as obesity and diabetes, there is an ever increasing need to dissect and understand the complex regulatory network underlying the multiple aspects of feeding behavior. In this minireview, we highlight the use of Drosophila in studying the neural circuits that control the feeding behavior in response to external and internal signals. In particular, we outline the work on the neuroanatomical and functional characterization of the newly identified hugin neuronal circuit. We focus on the pivotal role of the central nervous system in integrating external and internal feeding-relevant information, thus enabling the organism to make one of the most basic decisions – to eat or not to eat.
Utilization of DR1 as true RARE in regulating the Ssm, a novel retinoic acid-target gene in the mouse testis
Authors: Han Kyuyong , Song Haengseok , Moon Irene , Augustin Robert , Moley Kelle , Rogers Melissa , Lim Hyunjung
Published: March 2007

Various nuclear receptors form dimers to activate target genes via specific response elements located within promoters or enhancers. Retinoid X receptor (RXR) serves as a dimerization partner for many nuclear receptors including retinoic acid receptor (RAR) and peroxisome proliferator-activated receptor (PPAR). Dimers show differential preference towards directly repeated response elements with 1–5 nucleotide spacing, and direct repeat 1 (DR1) is a promiscuous element which recruits RAR/RXR, RXR/RXR, and PPAR/RXR in vitro. In the present investigation, we report identification of a novel RAR/RXR target gene which is regulated by DR1s in the promoter region. This gene, namely spermatocyte-specific marker (Ssm), recruits all the three combinations of nuclear receptors in vitro, but in vivo regulation is observed by trans-retinoic acid-activated RAR/RXR dimer. Indeed, chromatin immunoprecipitation experiment demonstrates binding of RARβ and RXRα in the promoter region of the Ssm. Interestingly, expression of Ssm is almost exclusively observed in spermatocytes in the adult mouse testis, where RA signaling is known to regulate developmental program of male germ cells. The results show that Ssm is a RAR/RXR target gene uniquely using DR1 and exhibits stage-specific expression in the mouse testis with potential function in later stages of spermatogenesis. This finding exemplifies usage of DR1s as retinoic acid response element (RARE) under a specific in vivo context.
Increased extracellular signal regulated kinases phosphorylation in the adrenal gland in response to chronic ACTH treatment
Authors: Ferreira Jorge G , Cruz Célia D , Neves Delminda , Pignatelli Duarte
Published: March 2007

ACTH released from the pituitary acts through activation of cAMP/PKA in adrenocortical cells stimulating steroidogenesis. Although ACTH was originally thought to have anti-proliferative effects on the adrenal, recently it has been described that it could also have proliferative effects acting through other signalling cascades. This is also relevant in humans given the increased levels of ACTH occurring together with adrenal cortex hyperplasia observed in Cushing’s disease and possibly in other situations such as chronic stress. One of the signalling pathways regulating cell proliferation is the extracellular signal regulated kinase (ERKs) pathway. ERKs are members of the MAPK family of cascades. They are activated by extracellular stimuli such as growth factors and mitogens, become phosphorylated through MEK1/2 and regulate a diversity of cellular processes such as proliferation and differentiation. Until now, no study addressed the effects of chronic ACTH administration on the activation of ERKs in vivo. Using rats submitted to different ACTH dosages as well as variable durations, we determined if ACTH induced ERKs activation and by establishing a parallelism with proliferating cell nuclear antigen (PCNA) expression, we aimed to demonstrate a role of ACTH-induced ERKs activation in cell proliferation. Blood was collected for hormonal analysis and the role of ACTH-induced ERKs activation in the stimulation of steroidogenesis was also studied. We confirmed that ACTH increased adrenal weight and corticosterone levels when compared with control or dexamethasone-treated animals. We also demonstrated that ACTH increases ERKs activation and PCNA expression in a time- and dose-dependent manner. When ERKs activation was blocked by the use of a specific MEK inhibitor (PD98059), there was a decrease in ACTH-induced corticosterone release and PCNA expression. We conclude that chronic ACTH induces ERKs activation and that this plays an important role in the induction of cell proliferation as well as steroidogenesis.
Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level
Authors: Radojević K , Arsenović-Ranin N , Kosec D , Pešić V , Pilipović I , Perišić M , Plećaš-Solarović B , Leposavić G
Published: March 2007

To test putative interdependence in the ontogenesis of the hypothalamic–pituitary–gonadal and thymic–lymphatic axes, thymocyte differentiation and maturation was examined in neonatally castrated (Cx) adult rats. In the hypercellular thymi of Cx rats, the proportion of the least mature CD4−CD8−TCRαβ− triple negative (TN) thymocytes was reduced, while the proportions of all downstream double positive (DP) subsets (TCRαβ−, TCRαβlow and TCRαβhigh) were increased when compared with neonatally sham-castrated (Sx) adult rats. This suggested an accelerated thymocyte transition from the TN to DP TCRαβlow developmental stage accompanied by an increased positive/ reduced negative thymocyte selection. The increased thymocyte surface density of Thy-1, which is implicated in thymocyte hyposensitivity to negative selection, in Cx rats further supports the previous assumption. The finding that the proportions of both single positive (SP) TCRαβhigh thymocyte subsets were reduced, while their numbers were increased (CD4+CD8−) or unaltered (CD4−CD8+), coupled with results demonstrating an increased level of CD4−CD8+ cells without changes in that of CD4+8− cells in the spleen indicate: (i) accelerated differentiation and maturation of the positively selected DP TCRαβhigh thymocytes towards CD4−8+ TCRαβhigh cells followed by increased emigration of the mature cells and (ii) decelerated differentiation and maturation towards CD4+8−TCRαβhigh cells in Cx rats. Furthermore, the unaltered proportion of intrathymically developing CD4+CD25+Foxp3+ regulatory cells in Cx rats, in light of putative hyposensitivity of thymocytes to negative selection suggesting reduced elimination of autoreactive cells, may provide a firm basis for understanding the reasons behind increased susceptibility of Cx rats to autoimmune disease induction.
Rock socket piles at Mall of the Emirates, Dubai
Authors: Alrifai L.
Published: March 2007

The first snow centre in the Middle East, Ski Dubai, was constructed as part of the Mall of the Emirates retail and leisure complex in Dubai, United Arab Emirates. Opened in December 2005, the project comprises an 80 m high indoor ski slope and associated structures. The higher end of the slope spans over a three-level car park. The site is underlain by a variable sequence of very loose/loose silty sands, which in turn overlie solid geology comprising very weak/weak carbonate sandstone. It has been considered that the most appropriate foundation option to support the structure safely is a piled foundation. Bored and cast-in-place piles socketed into the rock were proposed. Detailed analyses of single piles and pile groups under axial and lateral loading conditions were undertaken. The seismicity and liquefaction potential were considered in the design in accordance with the requirements of Dubai Municipality. The preliminary test piles, which were carried out prior to the installation of the working piles, checked the pile capacity and load–settlement behaviour, confirmed the effectiveness of the piling technique used, and provided greater assurance of the satisfactory performance of the foundations. The results of the preliminary pile-testing programme were compared with those obtained from theoretical predictions based on the empirical relationships between pile capacity and the unconfined compressive strength. On the basis of this review, a guide for the design of rock socket piles in weak carbonate rocks suitable for use in Dubai is proposed.
A nature conservation perspective of port-related dredging
Authors: Morris R.
Published: March 2007

The majority of UK ports, and especially those in England, lie within estuaries or on coastlines that are designated as Special Areas of Conservation (SAC), Special Protection Areas (SPAs) and Ramsar sites for their international wildlife interest. The EC Habitats Directive establishes an audit trail for evaluation of commercial development and its impact on Natura 2000 sites (SAC and SPA). It is therefore inevitable that port activity will come under scrutiny, both in terms of capital projects and ongoing operations. Much experience has been gained since the Habitats Regulations passed into UK law in 1994. Dredging has been at the forefront of the debate because it has the potential to influence the way in which inter-tidal habitats evolve, maintain themselves and support wildlife interest. It is also highlighted as having possible impacts on fish, especially migratory fish for which some estuaries are designated. This paper explores some of the issues and the solutions that have been found.
Early Trabecular Bone Healing Around Titanium Implants: A Histologic Study in Rabbits
Authors: Slaets Elke , Carmeliet Geert , Naert Ignace , Duyck Joke
Published: March 2007

Background: A detailed insight into the early healing response of trabecular bone to unloaded titanium implants is lacking.

Methods: Cylindrical implants were inserted in the tibial epiphysis of rabbits and left to heal for 1 to 42 days. Samples were processed into paraffin or methylmethacrylate sections and histomorphometrically analyzed.

Results: A hematoma was observed after 1 and 3 days of implant placement. In addition, small fragments of bone trabeculae were detected around the implant as a result of the implant installment procedure. Soon, osteoclasts were observed resorbing these fragments, whereas osteoblasts incorporated them in strands of new bone, thereby making them difficult to distinguish from day 7 onward. At that time, osteoblasts were detected at the edges of the preexisting bone, actively depositing new bone, resulting in maximal osteoid deposition around the implant after 28 days (58%). After 7 days of healing, the presence of basic remodeling units in the surrounding bone was already maximal (P <0.05 versus t = 1 and 3 days). This remodeling activity, together with the new bone formation, provided a firm anchoring of the implant in the trabecular bone.

Conclusions: This study evaluated the early cellular events in trabecular bone surrounding titanium implants. The insertion of an implant into bone initiates a series of biologic processes, including the formation of a hematoma, shattered bone fragments adjacent to the implantation site, intensive bone remodeling, and the formation of new bone, eventually leading to the osseointegration of the implant.
Verruciform Xanthoma: Immunohistochemical Characterization of Xanthoma Cell Phenotypes
Authors: Rawal Swati Y. , Kalmar John R. , Tatakis Dimitris N.
Published: March 2007

Background: Verruciform xanthoma (VX) is a benign lesion that primarily affects the oral cavity, most frequently the gingiva. VX lesions are characterized by xanthoma cells (lipid‐laden macrophages or foam cells) found in the superficial connective tissue. To characterize these foam cells further, immunohistochemical techniques were used to investigate the presence of macrophage subpopulations in oral lesions of VX.

Methods: Sixteen biopsy samples of VX lesions from the oral cavity (six from gingiva, three from palate, and seven from other mucosa) were studied. Immunohistochemical analysis was performed using antibody probes to macrophage subpopulations, including RM3/1 (reparative), 25F9 (resident), and 27E10 (inflammatory). The percentage of antibody‐labeled foam cells was determined by visual counts of selected fields within lesional connective tissue.

Results: The proportion of VX lesions that demonstrated positive xanthoma cell reactivity with antibodies RM3/1, 25F9, and 27E10 was 100%, 88%, and 50%, respectively. Foam cells that stained positively with RM3/1, 25F9, and 27E10 represented 61.5% ± 19.6%, 51.8% ± 29.4%, and 10.9% ± 14.7% of the counted cells, respectively. When results were analyzed based on anatomic location (gingiva, palate, and other mucosa), there was no difference in the percentage of positively stained cells by anatomic site for any of the three antibodies (P >0.05). Similarly, there were no differences between masticatory (gingiva and palate) and other mucosa (P >0.05).

Conclusions: VX lesions contain primarily reparative and resident foam cells, with limited numbers of inflammatory macrophages, consistent with a chronic reactive process. These findings were independent of the anatomic site.
Differential Gene Expression of Periodontal Ligament Cells After Loading of Static Compressive Force
Authors: Lee Yeon‐Hee , Nahm Dong‐Seok , Jung Youn‐Kwan , Choi Je‐Yong , Kim Sahng Gyoon , Cho Michael , Kim Myung‐Hee , Chae Chang‐Hoon , Kim Seong‐Gon
Published: March 2007

Background: Compressive force is an important mechanical stimulus on the periodontal ligament (PDL) and is closely related to therapeutic tooth movement. In this study, early or late response genes related to the compressive stress in PDL cells were evaluated. Particularly, the expression of interleukin (IL)‐6, IL‐8, and alkaline phosphatase (ALP) was studied.

Methods: The primary cultured cells from PDL were grown in a three‐dimensional collagen gel, and received a continuous static compressive force (1.76 g/cm2). The expressed genes were screened by cDNA microarray assays for 2 or 12 hours after the initiation of the mechanical force application. The genes of interest that showed significant changes in expression in the cDNA microarray assay were analyzed further by quantitative reverse transcriptase polymerase chain reaction (RT‐PCR), enzyme‐linked immunoabsorbent assays (ELISA), and ALP assays.

Results: ALP, IL‐6, and IL‐8 were selected among the genes that significantly changed expression (/M/ >0.7) and subsequently were confirmed by quantitative RT‐PCR. The secreted protein concentrations for IL‐6, IL‐8, and ALP activity were measured at 72 hours after application of continuous static compressive force. The protein level of IL‐6 was significantly increased at 72 hours (P <0.001), but there was no significant change in IL‐8 (P >0.0‐). ALP activity was decreased ∼41.5% compared to the control (P = 0.015).

Conclusions: Considering that IL‐6 is a potent osteoclast activator and the compressive side of PDL during orthodontic tooth movement shows the resorption of calcified tissue, the changed expression of IL‐6 and ALP in response to the static compressive force in PDL cells may contribute to the orthodontic tooth movement or alveolar bone remodeling.
Local Application of Melatonin Into Alveolar Sockets of Beagle Dogs Reduces Tooth Removal–Induced Oxidative Stress
Authors: Cutando Antonio , Arana Carlos , Gómez‐Moreno Gerardo , Escames Germaine , López Ana , Ferrera María J. , Reiter Russel J. , Acuña‐Castroviejo Darío
Published: March 2007

Background: The antioxidant and anti‐inflammatory hormone melatonin is secreted by saliva into the oral cavity, where it may protect the mucosal and gingival tissues from radical damage. To date, no studies have addressed the potential beneficial role of melatonin in the acute inflammatory response that follows oral surgical interventions, especially tooth extractions. The aim of this study was to determine whether tooth extraction induces changes in plasma oxidative stress levels, and whether melatonin treatment may counteract these changes.

Methods: Maxillary and mandibular premolars and molars of 16 adult Beagle dogs were extracted under general anesthesia. Eight dogs were treated with 2 mg melatonin placed into the alveolar sockets, whereas the other eight dogs received only vehicle. Lipid peroxidation (LPO) and nitrite plus nitrate (NOx) levels were determined in plasma, whereas glutathione (GSH) and glutathione disulfide (GSSG) levels and glutathione peroxidase (GPx) and reductase (GRd) activities were measured in red blood cells before and 24 hours after tooth extraction.

Results: Removal of the premolars and molars caused a significant rise in plasma LPO and NOx levels and in the erythrocyte GSSG/GSH ratio, whereas melatonin treatment restored the normal values of these parameters. Also, melatonin slightly increased erythrocyte GRd activity without changing GPx activity.

Conclusion: For the first time to our knowledge, the results show that during the immediate postoperative period following tooth extraction, there is a significant increase of oxidative stress, which is counteracted by the administration of melatonin into the alveolar sockets.
Effects of Full‐Mouth Scaling and Root Planing in Conjunction With Systemically Administered Azithromycin
Authors: Gomi Kazuhiro , Yashima Akihiro , Nagano Takatoshi , Kanazashi Mikimoto , Maeda Nobuko , Arai Takashi
Published: March 2007

Background: One‐stage full‐mouth disinfection (FMD), in which full‐mouth scaling and root planing (SRP) is performed with adjunctive use of chlorhexidine, was introduced in 1995. There have been several reports on the effectiveness of this treatment protocol. However, FMD was reported to induce pyrexia frequently. We examined the effects of full‐mouth SRP in conjunction with azithromycin administered orally before SRP to control the number of bacteria. The purpose of this study was to compare the effects of full‐mouth SRP using azithromycin with conventional SRP.

Methods: Thirty‐four subjects (17 in the test group and 17 in the control group) with severe chronic periodontitis were selected. The subjects of the test group had azithromycin 3 days before full‐mouth SRP. Clinical parameters (probing depth [PD], gingival index [GI], bleeding on probing [BOP], and gingival crevicular fluid [GCF]), total number of bacteria, and number of black pigment‐producing rods (BPRs) were evaluated at baseline and 5, 13, and 25 weeks after baseline.

Results: All clinical parameters improved in the test group more than in the control group. In the bacteriologic examination, the total number of bacteria did not change during the examination. In the test group, BPRs were not detected until 13 weeks. However, BPRs were detected in the control group by 13 weeks.

Conclusion: It was shown that full‐mouth SRP using systemically administered azithromycin was a clinically and bacteriologically useful basic periodontal treatment for severe chronic periodontitis.