bluuebunny/crossref_metadata_2025 huggingface dataset:
Iron Fortification Reduces Blood Lead Levels in Children in Bangalore, India
Authors: Zimmermann Michael B. , Muthayya Sumithra , Moretti Diego , Kurpad Anura , Hurrell Richard F.
Published: June 2006

OBJECTIVE. Chronic lead poisoning and iron deficiency are concentrated in urban children from lower socioeconomic strata, and both impair neurocognitive development. Our study objective was to determine if iron fortification reduces blood lead levels in urban, lead-exposed, iron-deficient children in Bangalore, India.

DESIGN, SETTING, AND PARTICIPANTS. A randomized, double-blind, controlled school-based feeding trial was done in 5- to 13-year-old iron-deficient children (n = 186). At baseline, a high prevalence of lead poisoning was found in the younger children. Subsequently, all 5- to 9-year-old children participating in the trial (n = 134) were followed to determine if iron fortification would affect their blood lead levels.

INTERVENTION. Children were dewormed and fed 6 days/week for 16 weeks either an iron-fortified rice meal (∼15 mg of iron per day as ferric pyrophosphate) or an identical control meal without added iron. Feeding was directly supervised and compliance monitored.

OUTCOME MEASURES. Hemoglobin, serum ferritin, C-reactive protein, transferrin receptor, zinc protoporphyrin, and blood lead concentrations were measured.

RESULTS. The prevalence of iron deficiency was significantly reduced in the iron group (from 70% to 28%) compared with the control group (76% to 55%). There was a significant decrease in median blood lead concentration in the iron group compared with the control group. The prevalence of blood lead levels ≥10 μg/dL was significantly reduced in the iron group (from 65% to 29%) compared with the control group (68% to 55%).

CONCLUSIONS. Our findings suggest providing iron in a fortified food to lead-exposed children may reduce chronic lead intoxication. Iron fortification may be an effective and sustainable strategy to accompany environmental lead abatement.
Antibiotic Treatment of Wheezing in Children With Asthma: What Is the Practice?
Authors: Kozyrskyj Anita L. , Dahl Matthew E. , Ungar Wendy J. , Becker Allan B. , Law Barbara J.
Published: June 2006

OBJECTIVE. Antibiotics are not recommended for the treatment of wheezing in children with asthma, but little is known about their use. This study was undertaken to evaluate trends and determinants of antibiotic use in children with wheezing during the fiscal years 1995 through 2001.

METHODS. Using the population-based health care and prescription databases in Manitoba, Canada, this descriptive study examined time trends in antibiotic prescription use for wheezing episodes in a population of children with asthma. The likelihood of receiving an antibiotic prescription according to child and physician characteristics also was determined. Annual population-based rates of antibiotic prescriptions for wheezing episodes were modeled by age and antibiotic class, using general estimating equations. The odds ratio for receiving an antibiotic prescription according to child demographics and physician factors was determined from hierarchical linear modeling.

Results. The antibiotic prescription rate for wheezing decreased by 28% from 708 prescriptions per 1000 children with asthma in 1995 to 511 prescriptions in 2001. Fifteen-fold increases in use were observed for broader spectrum macrolides in preschool children. Twenty-three percent of physician visits for wheezing resulted in an immediate antibiotic prescription, but this percentage increased to 64% for antibiotics that were received within 7 days of the episode. General practitioners prescribed antibiotics more often than did pediatricians. Physicians who were not trained in Canada or the United States were 40% more likely to prescribe antibiotics than their counterparts.

CONCLUSIONS. Antibiotic use for wheezing in children declined in the 1990s, but the increased use of broader spectrum macrolides has implications for antibiotic resistance. A link between antibiotic prescribing and physician specialty and location of training identifies opportunities for intervention.
Trends in Doctor Consultations, Antibiotic Prescription, and Specialist Referrals for Otitis Media in Children: 1995–2003
Authors: Plasschaert Astrid I.O. , Rovers Maroeska M. , Schilder Anne G. M. , Verheij Theo J. M. , Hak Eelko
Published: June 2006

BACKGROUND. Reported trends regarding the incidence of otitis media and antibiotic prescription rates are inconsistent.

OBJECTIVE. Our goal was to assess changes in incidence of consultation rates, antibiotic prescription, and referral rates for otitis media in children over the years 1995–2003.

METHODS. A cohort study including all children aged 0 to 13 years within the research database of the Netherlands University Medical Center Utrecht Primary Care Network covering the period 1995–2003. Otitis media diagnoses were recorded according to the International Classification of Primary Care codes and antibiotic prescription according to the Anatomic Therapeutic Chemical Classification System codes. Otitis media incidence rates were calculated as episodes per 1000 person-years. Antibiotic prescription and referral rates were calculated per 100 otitis media episodes.

RESULTS. From 1995 to 2003, the overall general practitioner consultation rates for acute otitis media and otitis media with effusion declined by 9% and 34%, respectively. In children aged 2 to 6 years and those aged 6 to 13 years, the incidence rates of acute otitis media and otitis media with effusion declined by 15% and 41% and 40% and 48%, respectively. In children <2 years of age, the incidence rates of acute otitis media and otitis media with effusion increased by 46% and 66%, respectively. Antibiotic prescription rates for acute otitis media and otitis media with effusion increased by 45% and 25%, respectively. The referral rate for acute otitis media did not change, whereas the referral rate for otitis media with effusion increased by 45%.

CONCLUSIONS. Consultation rates for otitis media have changed considerably over the last decade, and so have antibiotic prescriptions and specialist referrals. The rising antibiotic prescription rate for otitis media causes concern, because this may induce increasing medical costs and antibiotic resistance.
Emotional, Developmental, and Behavioral Health of American Children and Their Families: A Report From the 2003 National Survey of Children's Health
Authors: Blanchard Laura T. , Gurka Matthew J. , Blackman James A.
Published: June 2006

BACKGROUND. Recent children's health surveys have documented a high prevalence of emotional, developmental, and behavioral problems among children. Data from the 2003 National Survey of Children's Health provide new insights into these problems and their association with family function and community participation. These issues have become a current focus of the World Health Organization.

METHODS. Answers to questions of interest from the 2003 National Survey of Children's Health were reported using estimates and SEs of rates. Statistical comparisons of rates with χ2 tests at the 0.05 level were made when relevant.

RESULTS. The most commonly diagnosed problems among children 6–17 years of age were learning disabilities (11.5%), attention-deficit/hyperactivity disorder (8.8%), and behavioral problems (6.3%); among preschoolers, speech problems (5.8%) and developmental delay (3.2%) were most common. One in 200 children was diagnosed with autism. In contrast, rates of parental concerns about emotional, developmental, or behavioral problems were much higher; for example, 41% of parents had concerns about learning difficulties and 36% about depression or anxiety. Children with developmental problems had lower self-esteem, more depression and anxiety, more problems with learning, missed more school, and were less involved in sports and other community activities. Their families experienced more difficulty in the areas of childcare, employment, parent-child relationships, and caregiver burden.

CONCLUSIONS. The most recent National Survey of Children's Health mirrored results of previous surveys regarding rates of diagnosed emotional, developmental, and behavioral problems, including an escalating diagnosis of autism among children. Reported rates of parental concerns about these problems were much higher, suggesting possible underdiagnosis of children's problems. Children with chronic problems had diminished family functioning, more school absences, and less participation in community activities compared with other children. Their parents experienced more difficulty with childcare, employment, and parenting skills. A change in treatment emphasis is needed, away from an exclusive focus on a child's developmental and behavioral problems to one that addresses the impacts of these problems on the family and community participation. A new approach to the way these issues are addressed and managed has the potential to enhance the quality of life for a child, as well as the parents, and to produce more meaningful and tangible solutions to these complex and increasingly evident problems.
Empiric First-line Antibiotic Treatment of Acute Otitis in the Era of the Heptavalent Pneumococcal Conjugate Vaccine
Authors: Garbutt Jane , Rosenbloom Isabel , Wu Jenny , Storch Gregory A.
Published: June 2006

OBJECTIVES. Our goal was to estimate the local prevalence of Streptococcus pneumoniae nonsusceptible to penicillin and amoxicillin after widespread use of the heptavalent pneumococcal vaccine and to revise community-specific recommendations for first-line antibiotic treatment of acute otitis media.

METHODS. We conducted serial prevalence surveys between 2000 and 2004 in the offices of community pediatricians in St Louis, Missouri. Study participants were children <7 years of age with acute upper respiratory infections. Children treated with an antibiotic in the past 4 weeks were excluded. S pneumoniae was isolated from nasopharyngeal swabs using standard techniques. Isolates with a penicillin minimum inhibitory concentration >2 μg/mL were considered to be S pneumoniae nonsusceptible to amoxicillin.

RESULTS. There were 327 patients enrolled in the study. Between 2000 and 2004, vaccine coverage with ≥3 doses of heptavalent pneumococcal vaccine increased from 0% to 54%, but nasopharyngeal carriage of S pneumoniae was stable at 39%. The prevalence of S pneumoniae nonsusceptible to penicillin fell from 25% to 12% among patients, did not vary if <2 years of age, was reduced in children with ≥3 doses of heptavalent pneumococcal vaccine, and increased in child care attendees but reduced in attendees who had ≥3 doses of heptavalent pneumococcal vaccine. The prevalence of S pneumoniae nonsusceptible to amoxicillin in patients remained <5%.

CONCLUSIONS. In our community, widespread use of heptavalent pneumococcal vaccine has reduced the prevalence of S pneumoniae nonsusceptible to penicillin, and the prevalence of S pneumoniae nonsusceptible to amoxicillin remains low (<5%). If antibiotic treatment is elected for children with uncomplicated acute otitis media, we recommend treatment with standard-dose amoxicillin (40–45 mg/kg per day) for children with ≥3 doses of heptavalent pneumococcal vaccine, regardless of age and child care status. High-dose amoxicillin should be used for children with <3 doses of heptavalent pneumococcal vaccine and those treated recently with an antibiotic.
Update of Newborn Screening and Therapy for Congenital Hypothyroidism
Authors:   American Academy of Pediatrics, Rose Susan R. ,   and the Section on Endocrinology and Committee on Genetics,   American Thyroid Association, Brown Rosalind S. ,   and the Public Health Committee,   Lawson Wilkins Pediatric Endocrine Society
Published: June 2006

This Clinical Report was revised. See https://doi.org/10.1542/peds.2022-060419.

Unrecognized congenital hypothyroidism leads to mental retardation. Newborn screening and thyroid therapy started within 2 weeks of age can normalize cognitive development. The primary thyroid-stimulating hormone screening has become standard in many parts of the world. However, newborn thyroid screening is not yet universal in some countries. Initial dosage of 10 to 15 μg/kg levothyroxine is recommended. The goals of thyroid hormone therapy should be to maintain frequent evaluations of total thyroxine or free thyroxine in the upper half of the reference range during the first 3 years of life and to normalize the serum thyroid-stimulating hormone concentration to ensure optimal thyroid hormone dosage and compliance.

Improvements in screening and therapy have led to improved developmental outcomes in adults with congenital hypothyroidism who are now in their 20s and 30s. Thyroid hormone regimens used today are more aggressive in targeting early correction of thyroid-stimulating hormone than were those used 20 or even 10 years ago. Thus, newborn infants with congenital hypothyroidism today may have an even better intellectual and neurologic prognosis. Efforts are ongoing to establish the optimal therapy that leads to maximum potential for normal development for infants with congenital hypothyroidism.

Remaining controversy centers on infants whose abnormality in neonatal thyroid function is transient or mild and on optimal care of very low birth weight or preterm infants. Of note, thyroid-stimulating hormone is not elevated in central hypothyroidism. An algorithm is proposed for diagnosis and management.

Physicians must not relinquish their clinical judgment and experience in the face of normal newborn thyroid test results. Hypothyroidism can be acquired after the newborn screening. When clinical symptoms and signs suggest hypothyroidism, regardless of newborn screening results, serum free thyroxine and thyroid-stimulating hormone determinations should be performed.
Clinical Genetic Evaluation of the Child With Mental Retardation or Developmental Delays
Authors: Moeschler John B. , Shevell Michael ,   and the Committee on Genetics
Published: June 2006

This Clinical Report was revised. See https://doi.org/10.1542/peds.2014-1839.

This clinical report describes the clinical genetic evaluation of the child with developmental delays or mental retardation. The purpose of this report is to describe the optimal clinical genetics diagnostic evaluation to assist pediatricians in providing a medical home for children with developmental delays or mental retardation and their families. The literature supports the benefit of expert clinical judgment by a consulting clinical geneticist in the diagnostic evaluation. However, it is recognized that local factors may preclude this particular option. No single approach to the diagnostic process is supported by the literature. This report addresses the diagnostic importance of clinical history, 3-generation family history, dysmorphologic examination, neurologic examination, chromosome analysis (≥650 bands), fragile X molecular genetic testing, fluorescence in situ hybridization studies for subtelomere chromosome rearrangements, molecular genetic testing for typical and atypical presentations of known syndromes, computed tomography and/or magnetic resonance brain imaging, and targeted studies for metabolic disorders.
Estimating Yields of Salt‐ and Water‐Stressed Forages with Remote Sensing in the Visible and Near Infrared
Authors: Poss J. A. , Russell W. B. , Grieve C. M.
Published: June 2006

In arid irrigated regions, the proportion of crop production under deficit irrigation with poorer quality water is increasing as demand for fresh water soars and efforts to prevent saline water table development occur. Remote sensing technology to quantify salinity and water stress effects on forage yield can be an important tool to address yield loss potential when deficit irrigating with poor water quality. Two important forages, alfalfa (Medicago sativa L.) and tall wheatgrass (Agropyron elongatum L.), were grown in a volumetric lysimeter facility where rootzone salinity and water content were varied and monitored. Ground‐based hyperspectral canopy reflectance in the visible and near infrared (NIR) were related to forage yields from a broad range of salinity and water stress conditions. Canopy reflectance spectra were obtained in the 350‐ to 1000‐nm region from two viewing angles (nadir view, 45° from nadir). Nadir view vegetation indices (VI) were not as strongly correlated with leaf area index changes attributed to water and salinity stress treatments for both alfalfa and wheatgrass. From a list of 71 VIs, two were selected for a multiple linear‐regression model that estimated yield under varying salinity and water stress conditions. With data obtained during the second harvest of a three‐harvest 100‐d growing period, regression coefficients for each crop were developed and then used with the model to estimate fresh weights for preceding and succeeding harvests during the same 100‐d interval. The model accounted for 72% of the variation in yields in wheatgrass and 94% in yields of alfalfa within the same salinity and water stress treatment period. The model successfully predicted yield in three out of four cases when applied to the first and third harvest yields. Correlations between indices and yield increased as canopy development progressed. Growth reductions attributed to simultaneous salinity and water stress were well characterized, but the corrections for effects of varying tissue nitrogen (N) and very low leaf area index (LAI) are necessary.
Utilization of Biosolids during the Phytoremediation of Hydrocarbon‐Contaminated Soil
Authors: Dickinson S. J. , Rutherford P. M.
Published: June 2006

Addition of anaerobically digested sewage sludge (biosolids) to soil may improve conditions for phytoremediation of petroleum hydrocarbons (PHCs) through improved soil chemical, biological, and physical properties. A 32‐wk greenhouse study investigated three rates of biosolids addition (0, 13.34, and 26.68 g oven‐dry biosolids kg−1 oven‐dry soil) and the presence or absence of smooth brome (Bromus inermis Leyss. cv. Carlton) plants on the removal of diesel (3.5 g kg−1 oven‐dry soil) in an industrial, sandy loam soil. Diesel PHCs were divided into two fractions based on equivalent normal straight‐chain boiling point ranges (F2: nC10‐nC16; F3: nC16‐nC34). The addition of biosolids did not increase the extent of PHC degradation but did result in significantly greater first‐order decay constants compared to unamended controls. Overall, the presence of plants did not increase the rate or extent of PHC degradation, relative to that observed in unamended, non‐vegetated soils. Vegetation was, however, an important factor within the biosolids‐amended soils as was observed by a greater extent of PHC degradation. Some of this decrease was attributed to plant‐induced removal of biosolids components that were contributing to the F3 fraction. Overall, the low‐amendment rate (13.34 g oven‐dry biosolids kg−1 oven‐dry soil) was considered to be the most effective treatment because it produced the greatest overall PHC degradation rate (0.226 wk−1 for total PHCs) and resulted in the greatest recovery of biosolids‐derived N by smooth brome (26.6%).
Soil Amendments, Plant Age, and Intercropping Impact p,p′‐DDE Bioavailability to Cucurbita pepo
Authors: White Jason C. , Parrish Zakia D. , Gent Martin P. N. , Iannucci‐Berger William , Eitzer Brian D. , Isleyen Mehmet , Incorvia Mattina MaryJane
Published: June 2006

Field experiments were conducted to optimize the phytoextraction of weathered p,p′‐DDE (p,p′‐dichlorodiphenyldichloroethylene) by Cucurbita subspecies. The effects of two soil amendments, mycorrhizae or a biosurfactant, on p,p′‐DDE accumulation was determined. Also, p,p′‐DDE uptake was assessed during plant growth (12, 26, 38, and 62 d), and cultivars that accumulate weathered p,p′‐DDE were intercropped with cultivars known not to have that ability. Cucurbita pepo L. ssp. pepo accumulated large amounts of the contaminant, having stem bioconcentration factors, amounts of p,p′‐DDE translocated, and contaminant phytoextraction that were 14, 9.9, and 5.0 times greater than C. pepo L. ssp. ovifera (L.) D.S. Decker, respectively. During 62 d, the stem BCF (bioconcentration factor) for p,p′‐DDE in subspecies pepo remained constant and the total amount of contaminant accumulated was correlated with plant biomass (r2 = 0.86). For subspecies ovifera, the stem BCF was highest at 12 d (1.5) but decreased to 0.39 by 62 d, and p,p′‐DDE removal was not correlated with plant biomass. Mycorrhizal inoculation increased p,p′‐DDE accumulation by both subspecies by an average 4.4 times. For subspecies pepo, mycorrhizae increased the percentage of contaminant extracted from 0.72 to 2.1%. Biosurfactant amendment also enhanced contaminant accumulation by both subspecies, although treatment reduced subspecies ovifera biomass by 60%. The biosurfactant had no effect on the biomass of subspecies pepo, increased the average contaminant concentration by 3.6‐fold, and doubled the overall amount of p,p′‐DDE removed from the soil. Soil amendments that enhance the mobility of weathered persistent organic pollutants will significantly increase the amount of contaminant phytoextraction by Cucurbita pepo
Sorption Kinetics of Chlortetracyline and Tylosin on Sandy Loam and Heavy Clay Soils
Authors: Allaire S. E. , Del Castillo J. , Juneau V.
Published: June 2006

Antibiotics may appear in the environment when manure, sewage sludge, and other organic amendments are added to soils. There is concern that the presence of antibiotics in soils may lead to the development of antibiotic‐resistant bacteria which may spread to the rest of the environment. This paper aims at evaluating the sorption kinetics of two antibiotics frequently used in pig production. The results indicate that sorption of chlortetracycline (CTC) and tylosin (TYL) in sandy loam and clay occurs very fast. More than 95% of the CTC adsorption is completed within 10 min on both soils and of TYL within 3 h. These results suggest that 24‐h soil and antibiotic solution mixtures is enough for sorption studies. Also, there is less likelihood that these antibiotics will leach through soil and appear in the ground water since their sorption on soils is very high unless they are carried by soil particles through preferential flow. There was also no effect of soil sterilization on sorption kinetics of these antibiotics thus suggesting that there is minimal probability of the antibiotics degrading by microorganisms during 24‐ to 48‐h adsorption studies.
Nonlinear and Competitive Sorption of Apolar Compounds in Black Carbon‐Free Natural Organic Materials
Authors: Pignatello Joseph J. , Lu Yuefeng , LeBoeuf Eugene J. , Huang Weilin , Song Jianzhong , Xing Baoshan
Published: June 2006

Numerous studies have reported a spectrum of sorption phenomena in soils, sediments, and organic matter isolates of those materials that are inconsistent with a partition model proposed in the late 1970s and early 1980s, a model predicated on a hypothesis that sorption is linear and noncompetitive. To explain these nonideal phenomena, prior studies have proposed a hard‐soft (glassy‐rubbery) model for SOM (soil and sediment organic matter), while others have attributed them singularly to BC (black carbon: soot and charcoal) particles present in topsoils and sediments. In this study, we demonstrated nonideal sorption behavior (isotherm nonlinearity, competitive effects) for a group of apolar compounds in a large set of natural and model organic materials, including a commercial lignin and humic acids from different sources. Complete oxidation of samples by an acidic dichromate method was taken to signify the absence of BC. (However, polymethylene units are stable even if functionalized on both ends, making the technique unreliable for quantifying BC.) Other samples were inferred free of BC by their source and method of preparation. Characterization by thermalanalytical methods indicated the glassy character of the organic materials. The origin of the nonideal behaviors appears to be the glassy character of these materials. Sorption nonlinearity increased or decreased by changing temperature, cosolvent content, or degree of cross‐linking by metal ions as predicted for organic solids in a glassy state. We conclude that macromolecular humic substances in the environment may exhibit nonideal sorption behavior in soils and sediments, quite apart from any such behaviors attributable to BC.
Mesocosm‐Scale Evaluation of Faunal and Microbial Communities of Aerated and Unaerated Leachfield Soil
Authors: Amador José A. , Potts David A. , Savin Mary C. , Tomlinson Peter , Görres Josef H. , Nicosia Erika L.
Published: June 2006

Aeration improves the capacity of leachfields to decontaminate and reduce the nutrient load of wastewater. To gain a better understanding of the effects of aeration, we examined the faunal and microbial communities of septic system leachfield soil (0‐4 and 4‐13 cm) using replicated (n= 3) mesocosms that were actively aerated (AIR) or unaerated (LEACH). Protozoa were 40 to 140 times more abundant in AIR than in LEACH soil. No nematodes were found in LEACH soil, whereas AIR soil contained 5 to 14 × 103nematodes (all bacteriovores) kg−1Active microbial biomass was four to five times higher in AIR than LEACH soil. Proteobacteria and actinomycetes/sulfate‐reducing bacteria constituted a higher proportion of the community in AIR soil, whereas anaerobic Gram‐negative bacteria/firmicutes were more prominent in LEACH soil. Ratios of prokaryotic to eukaryotic phospholipid fatty acids (PLFAs) were higher in LEACH soil, as were membrane stress index values, whereas the starvation index was higher in AIR soil. Community‐level physiological profiles showed that 29 and 30 different substrates were used for growth by LEACH and AIR soil microorganisms, respectively. The AIR soil had more microorganisms capable of growing on 10 substrates, whereas growth on two substrates was higher in LEACH soil. Polymerase chain reaction‐denaturing gradient gel electrophoresis (PCR‐DGGE) analysis of 16S rRNA gene fragments revealed greater diversity of dominant phylotypes in AIR than LEACH soil, with communities separated by treatment. Aerated leachfield soil had a larger and more diverse faunal and microbial community than unaerated soil, possibly due to differences in the type and availability of electron acceptors.
Relationships among Nutrients, Chlorophyll‐a, and Dissolved Oxygen in Agricultural Streams in Illinois
Authors: Morgan Allyson M. , Royer Todd V. , David Mark B. , Gentry Lowell E.
Published: June 2006

A better understanding of the controls on algae and dissolved O2 in agricultural streams of Illinois is needed to aid in development of nutrient standards. We investigated the relationships between dissolved nutrients, algal abundance, and dissolved O2 in five streams in east‐central Illinois from March through November 2004. The streams drained watersheds from 25 to 777 km2 that were dominated by row crop agriculture. Three sites had open canopies and two were bordered by a narrow forest of deciduous trees. Algal abundance was measured as chlorophyll‐a (chl‐a) concentration in the water column (sestonic) and on the streambed (periphytic). Mean NO3‐N concentrations ranged from 5.5 to 8.8 mg N L−1 and did not relate to algal abundance. Sestonic chl‐a values ranged from nearly zero to >15 mg m−3 with no differences between open and shaded streams and only a weak correlation with dissolved reactive P (mean concentrations were 44‐479 μg L−1). The results suggest that sestonic chl‐a is a poor criterion for assessing nutrient‐related problems in these streams. Greatest periphytic chl‐a occurred during low flow from August through October, but periphyton occurred consistently in only two of the five streams. The abundance of filamentous algae explained 64% of the variation in diel O2 saturation, but was not correlated with nutrients. Currently it appears that hydrology and light, rather than nutrients, control algal abundance in these streams, and in the agricultural landscape of east‐central Illinois, it may not be possible to reduce nutrient concentrations sufficiently to limit filamentous algal blooms.
Application of Two Organic Amendments on Soil Restoration: Effects on the Soil Biological Properties
Authors: Tejada M. , Hernandez M. T. , Garcia C.
Published: June 2006

One method for recovering degraded soils in semiarid regions is to add organic matter to improve soil characteristics, thereby enhancing biogeochemical nutrient cycling. In this paper, we studied the changes in soil biological properties as a result of adding a crushed cotton gin compost (CCGC) and a poultry manure (PM) for 4 yr to restore a Xerollic Calciorthid located near Seville (Guadalquivir Valley, Andalusia, Spain). Organic wastes were applied at rates of 5, 7.5, and 10 Mg organic matter ha−1 One year after the assay began, spontaneous vegetation had appeared in the treated plots, particularly in that receiving a high PM and CCGC dose. After 4 yr, the plant cover in these treated plots was around 88 and 79%, respectively, compared with 5% for the control. The effects on soil microbial biomass and six soil enzymatic activities (dehydrogenase, urease, BBA‐protease, β‐glucosidase, arylsulfatase, and alkaline phosphatase activities) were ascertained. Both added organic wastes had a positive effect on the biological properties of the soil, although at the end of the experimental period and at high dosage, soil microbial biomass and soil enzyme activities were generally higher in the PM‐amended soils compared to the CCGC‐amended soils. Enzyme activity from the PM‐amended soil was 5, 15, 13, 19, 22, 30, and 6% greater than CCGC‐amended soil for soil microbial biomass, urease, BBA‐protease, β‐glucosidase, alkaline phosphatase, arylsulfatase, and dehydrogenase activities, respectively. After 4 yr, the percentage of plant cover was >48% in all treated plots and 5% in the control.
Impaired Gene and Protein Expression of Exocytotic Soluble N-Ethylmaleimide Attachment Protein Receptor Complex Proteins in Pancreatic Islets of Type 2 Diabetic Patients
Authors: Ostenson Claes-Goran , Gaisano Herbert , Sheu Laura , Tibell Annika , Bartfai Tamas
Published: June 2006

Exocytosis of insulin is dependent on the soluble N-ethylmaleimide attachment protein receptor (SNARE) complex proteins in the B-cells. We assessed insulin release as well as gene and protein expression of SNARE complex protein in isolated pancreatic islets of type 2 diabetic patients (n = 4) and nondiabetic control subjects (n = 4). In islets from the diabetic patients, insulin responses to 8.3 and 16.7 mmol/l glucose were markedly reduced compared with control islets (4.7 ± 0.3 and 8.4 ± 1.8 vs. 17.5 ± 0.1 and 24.3 ± 1.2 μU · islet−1 · h−1, respectively; P < 0.001). Western blot analysis revealed decreased amounts of islet SNARE complex and SNARE-modulating proteins in diabetes: syntaxin-1A (21 ± 5% of control levels), SNAP-25 (12 ± 4%), VAMP-2 (7 ± 4%), nSec1 (Munc 18; 34 ± 13%), Munc 13-1 (27 ± 4%), and synaptophysin (64 ± 7%). Microarray gene chip analysis, confirmed by quantitative PCR, showed that gene expression was decreased in diabetes islets: syntaxin-1A (27 ± 2% of control levels), SNAP-25 (31 ± 7%), VAMP-2 (18 ± 3%), nSec1 (27 ± 5%), synaptotagmin V (24 ± 2%), and synaptophysin (12 ± 2%). In conclusion, these data support the view that decreased islet RNA and protein expression of SNARE and SNARE-modulating proteins plays a role in impaired insulin secretion in type 2 diabetic patients. It remains unclear, however, to which extent this defect is primary or secondary to, e.g., glucotoxicity.
Interactions Between Noncontiguous Haplotypes in the Adiponectin Gene ACDC Are Associated With Plasma Adiponectin
Authors: Woo Jessica G. , Dolan Lawrence M. , Deka Ranjan , Kaushal Ritesh D. , Shen Yayun , Pal Prodipto , Daniels Stephen R. , Martin Lisa J.
Published: June 2006

Adiponectin, an adipocyte protein important in insulin sensitization and cardioprotection, has a strong genetic component. We hypothesized that variants in the adiponectin gene (adipocyte collagen–domain containing [ACDC]) contribute to adiponectin levels in a biracial adolescent cohort. We genotyped 11 ACDC single nucleotide polymorphisms (SNPs) in 631 non-Hispanic white and 553 African-American unrelated adolescents in grades 5–12 randomly selected from the Princeton School District Study. ACDC SNPs −11,391 (A allele), −10,068 (G allele), and +276 (T allele) were associated with higher adiponectin, adjusting for sex, puberty stage, BMI Z score, and waist Z score. Contiguous two-SNP haplotypes of promoter variants −11,391/−10,068 were significantly associated with adiponectin levels in whites and African Americans (P < 0.0001 and 0.03, respectively). Extended haplotypes from the promoter through the second intron (−11,391 to +349) strongly associated with adiponectin in whites (P = 6 × 10−11) and African Americans (P = 0.004), but haplotypes of first intron SNPs −4,521 to −657 did not (P > 0.2). Noncontiguous haplotypes or interactions between two-SNP (−11,391/−10,068) and three-SNP (+45, +276, and +349) haplotypes predicted adiponectin better than either region alone. Variants of ACDC are associated with adiponectin levels in whites and African Americans. Interactions between noncontiguous ACDC haplotypes strongly influence adiponectin levels, suggesting nonadditive and potentially cis relationships between these regions.
Streptozotocin-Induced Diabetes Causes Astrocyte Death After Ischemia and Reperfusion Injury
Authors: Muranyi Marianna , Ding Chaonan , He QingPing , Lin Yanling , Li Ping-An
Published: June 2006

Diabetes exacerbates neuronal cell death induced by cerebral ischemia. One contributing factor is enhanced acidosis during ischemia. Astrocytes are vulnerable to hypoxia under acidic conditions in vitro and may be targets of ischemia under diabetic conditions. The objective of this study was to determine whether diabetes would cause damage to astrocytes after an ischemic brain injury in vivo. Diabetic and nondiabetic rats were subjected to 5 min of forebrain ischemia and followed by 30 min, 6 h, or 1 or 3 days of recovery. The results showed that ischemia caused activation of astrocytes in nondiabetic rats. In contrast, diabetes caused astrocyte activation in early stage of reperfusion and astrocyte death in late stage of reperfusion. Remarkable astrocyte death was preceded by increased DNA oxidation. Further studies revealed that increased astrocyte damage coincided with enhanced production of free radicals. These data suggest that hyperglycemic ischemia worsens outcome in astrocytes, as it does in neurons.
Microvascular Disease in Type 1 Diabetes Alters Brain Activation
Authors: Wessels Alette M. , Rombouts Serge A.R.B. , Simsek Suat , Kuijer Joost P.A. , Kostense Piet J. , Barkhof Frederik , Scheltens Philip , Snoek Frank J. , Heine Robert J.
Published: June 2006

Individuals with type 1 diabetes have mild performance deficits on a range of neuropsychological tests compared with nondiabetic control subjects. The mechanisms underlying this cognitive deterioration are still poorly understood, but chronic hyperglycemia is now emerging as a potential determinant, possibly through microvascular changes in the brain. In 24 type 1 diabetic patients, we tested at euglycemia and at acute hypoglycemia whether the presence of proliferative diabetic retinopathy, as a marker of microvascular disease, adversely affects the ability of the brain to respond to standardized hypoglycemia, using functional magnetic resonance imaging with a cognitive task. Patients with retinopathy, compared with patients without, showed less deactivation (hence, an increased response) in the anterior cingulate and the orbital frontal gyrus during hypoglycemia compared with euglycemia (P < 0.05). Task performance and reaction time were not significantly different for either group. We conclude that microvascular damage in the brain of patients with retinopathy caused this increased brain response to compensate for functional loss.
Considerations in the Design of Hyperinsulinemic-Euglycemic Clamps in the Conscious Mouse
Authors: Ayala Julio E. , Bracy Deanna P. , McGuinness Owen P. , Wasserman David H.
Published: June 2006

Despite increased use of the hyperinsulinemic-euglycemic clamp to study insulin action in mice, the effects of experimental parameters on the results obtained have not been addressed. In our studies, we determined the influences of sampling sites, fasting duration, and insulin delivery on results obtained from clamps in conscious mice. Carotid artery and jugular vein catheters were implanted in C57BL/6J mice (n = 6–10/group) fed a normal diet for sampling and infusions. After a 5-day recovery period, mice underwent a 120-min clamp (2.5-mU · kg−1 · min−1 insulin infusion; ∼120–130 mg/dl glucose) while receiving [3-3H]glucose to determine glucose appearance (endoRa) and disappearance (Rd). Sampling large volumes (∼100 μl) from the cut tail resulted in elevated catecholamines and basal glucose compared with artery sampling. Catecholamines were not elevated when taking small samples (∼ 5 μl) from the cut tail. Overnight (18-h) fasting resulted in greater loss of total body, lean, and fat masses and hepatic glycogen but resulted in enhanced insulin sensitivity compared with 5-h fasting. Compared with a 16-mU/kg insulin prime, a 300-mU/kg prime resulted in hepatic insulin resistance and slower acquisition of steady-state glucose infusion rates (GIR) after a 5-h fast. The steady-state GIR was expedited after the 300-mU/kg prime in 18-h–fasted mice. The GIR and Rd rose with increasing insulin infusions (0.8, 2.5, 4, and 20 mU · kg−1 · min−1), but endoRa was fully suppressed with doses higher than 0.8 mU · kg−1 · min−1. Thus, common variations in experimental factors yield different results and should be considered in designing and interpreting clamps.
Differences of Pancreatic Expression of 7B2 Between C57BL/6J and C3H/HeJ Mice and Genetic Polymorphisms at its locus (Sgne1)
Authors: Schmidt Gunther , Sirois Francine , Anini Younes , Kauri Lisa M. , Gyamera-Acheampong Charles , Fleck Eckart , Scott Fraser W. , Chrétien Michel , Mbikay Majambu
Published: June 2006

C57BL/6 (B6) mice develop glucose intolerance with age, whereas C3H/He (C3H) mice do not. In this study, we examined whether this differential glucose homeostasis was associated with differences of proteolytic activation of pancreatic prohormones. Radioimmunoassays showed comparable levels of fasting plasma insulin between the two strains but a significantly lower glucagon level in B6 mice. Pulse-chase analysis of glucagon biosynthesis in isolated pancreatic islets revealed that proglucagon was less efficiently processed in B6 mice. Because proprotein convertase (PC)2 and its 7B2 helper protein are required for this processing, we quantified islet mRNA levels by RT-PCR and protein levels by immunoblotting. The levels of proPC2 mRNA were similar between the two strains, but B6 protein extracts contained less of the mature PC2. In contrast, 7B2 mRNA and protein levels were both significantly lower in B6 pancreas. Sequencing of the 7B2 gene promoter and cDNA in the two strains revealed seven single nucleotide polymorphisms and one dinucleotide insertion/deletion in the cDNA as well as a single nucleotide polymorphism and two insertions/deletions in the promoter. Differential expression of 7B2 may contribute to the difference between B6 and C3H mice not only in glucagon production and secretion but also in glucose tolerance.
Genetic Architecture of the APM1 Gene and Its Influence on Adiponectin Plasma Levels and Parameters of the Metabolic Syndrome in 1,727 Healthy Caucasians
Authors: Heid Iris M. , Wagner Stefanie A. , Gohlke Henning , Iglseder Bernhard , Mueller Jakob C. , Cip Paula , Ladurner Günther , Reiter Raphael , Stadlmayr Andreas , Mackevics Vitolds , Illig Thomas , Kronenberg Florian , Paulweber Bernhard
Published: June 2006

The associations of the adiponectin (APM1) gene with parameters of the metabolic syndrome are inconsistent. We performed a systematic investigation based on fine-mapped single nucleotide polymorphisms (SNPs) highlighting the genetic architecture and their role in modulating adiponectin plasma concentrations in a particularly healthy population of 1,727 Caucasians avoiding secondary effects from disease processes. Genotyping 53 SNPs (average spacing of 0.7 kb) in the APM1 gene region in 81 Caucasians revealed a two-block linkage disequilibrium (LD) structure and enabled comprehensive tag SNP selection. We found particularly strong associations with adiponectin concentrations for 11 of the 15 tag SNPs in the 1,727 subjects (five P values <0.0001). Haplotype analysis provided a thorough differentiation of adiponectin concentrations with 9 of 17 haplotypes showing significant associations (three P values <0.0001). No significant association was found for any SNP with the parameters of the metabolic syndrome. We observed a two-block LD structure of APM1 pointing toward at least two independent association signals, one including the promoter SNPs and a second spanning the relevant exons. Our data on a large number of healthy subjects suggest a clear modulation of adiponectin concentrations by variants of APM1, which are not merely a concomitant effect in the course of type 2 diabetes or coronary artery disease.
Gestational Glucose Tolerance and Risk of Type 2 Diabetes in Young Pima Indian Offspring
Authors: Franks Paul W. , Looker Helen C. , Kobes Sayuko , Touger Leslie , Tataranni P. Antonio , Hanson Robert L. , Knowler William C.
Published: June 2006

The in utero environment is a powerful risk factor for type 2 diabetes in offspring, but little is known about the risk conveyed by nondiabetic gestational glucose levels. This issue was explored in 911 nondiabetic Pima Indian mothers and 1,436 of their children. Associations were assessed in multivariate models between maternal third trimester glucose tolerance and indexes of body composition and glycemic control in their children. At parturition, the mothers’ ages ranged from 14 to 43 years. Offspring were studied at age 0–39 years. An SD (1.3 mmol/l) of maternal glucose was associated with 56 g higher birth weight (P = 0.0002). This effect persisted when only offspring of normal glucose tolerant mothers were examined (57 g, P < 0.0001). In Cox proportional hazards models, the adjusted hazard rate ratio for offspring risk of diabetes per SD maternal glucose was 1.6 (95% CI 1.3–2.0, P < 0.0001). When only offspring of normal glucose tolerant mothers were examined, the risk was reduced but remained significant (1.3 [1.04–1.71], P = 0.026). In conclusion, maternal glycemia during pregnancy is associated with increased birth weight and risk of diabetes in Pima Indian offspring, even when mothers are normal glucose tolerant during pregnancy. Thus, prevention of offspring type 2 diabetes may require strategies that focus on improving gestational glucose tolerance even within the normal range.
MafB
Authors: Artner Isabella , Le Lay John , Hang Yan , Elghazi Lynda , Schisler Jonathan C. , Henderson Eva , Sosa-Pineda Beatriz , Stein Roland
Published: June 2006

The large Maf family of basic leucine-zipper–containing transcription factors are known regulators of key developmental and functional processes in various cell types, including pancreatic islets. Here, we demonstrate that within the adult pancreas, MafB is only expressed in islet α-cells and contributes to cell type–specific expression of the glucagon gene through activation of a conserved control element found between nucleotides −77 to −51. MafB was also shown to be expressed in developing α- and β-cells as well as in proliferating hormone-negative cells during pancreatogenesis. In addition, MafB expression is maintained in the insulin+ and glucagon+ cells remaining in mice lacking either the Pax4 or Pax6 developmental regulators, implicating a potentially early role for MafB in gene regulation during islet cell development. These results indicate that MafB is not only important to islet α-cell function but may also be involved in regulating genes required in both endocrine α- and β-cell differentiation.
Insulin Improves Myocardial Blood Flow in Patients With Type 2 Diabetes and Coronary Artery Disease
Authors: Lautamäki Riikka , Airaksinen K.E. Juhani , Seppänen Marko , Toikka Jyri , Härkönen Risto , Luotolahti Matti , Borra Ronald , Sundell Jan , Knuuti Juhani , Nuutila Pirjo
Published: June 2006

Insulin infusion improves myocardial blood flow (MBF) in healthy subjects. Until now, the effect of insulin on myocardial perfusion in type 2 diabetic subjects with coronary artery disease (CAD) has been unknown. We studied the effects of insulin on MBF in ischemic regions evaluated by single-photon emission–computed tomography and coronary angiography and in nonischemic regions in 43 subjects (ages 63 ± 7 years) with type 2 diabetes (HbA1c 7.1 ± 0.9%). MBF was measured at fasting and during a euglycemic-hyperinsulinemic clamp at rest (n = 43) and during adenosine-induced (140 μg · kg−1 · min−1 for 7 min) hyperemia (n = 26) using positron emission tomography and 15O-labeled water. MBF was significantly attenuated in ischemic regions as compared with in nonischemic regions (P < 0.0001) and was increased by insulin as compared with in the fasting state (P < 0.0001). At rest, insulin infusion increased MBF by 13% in ischemic regions (P = 0.043) and 22% in nonischemic regions (P = 0.003). During adenosine infusion, insulin enhanced MBF by 20% (P = 0.018) in ischemic regions and 18% (P = 0.045) in nonischemic regions. In conclusion, insulin infusion improved MBF similarly in ischemic and nonischemic regions in type 2 diabetic subjects with CAD. Consequently, in addition to its metabolic effects, insulin infusion may improve endothelial function and thus increase the threshold for ischemia and partly contribute to the beneficial effects found in clinical trials in these subjects.
Activation of the AMP-Activated Kinase by Antidiabetes Drug Metformin Stimulates Nitric Oxide Synthesis In Vivo by Promoting the Association of Heat Shock Protein 90 and Endothelial Nitric Oxide Synthase
Authors: Davis Bradley J. , Xie Zhonglin , Viollet Benoit , Zou Ming-Hui
Published: June 2006

Metformin, one of most commonly used drugs for the treatment of type 2 diabetes, improves vascular endothelial functions and reduces cardiovascular events in patients with type 2 diabetes, although its mechanisms remain unknown. The current study aimed to elucidate how metformin improves endothelial functions. Exposure of cultured bovine aortic endothelial cells (BAECs) to clinically relevant concentrations of metformin (50–500 μmol/l) dose-dependently increased serine-1179 (Ser1179) phosphorylation (equal to human Ser1179) of endothelial nitric oxide (NO) synthase (eNOS) as well as its association with heat shock protein (hsp)-90, resulting in increased activation of eNOS and NO bioactivity (cyclic GMP). These effects of metformin were mimicked or completely abrogated by adenoviral overexpression of a constitutively active 5′-AMP–activated kinase (AMPK) mutant or a kinase-inactive AMPK-α, respectively. Furthermore, administration of metformin as well as 5-aminoimidazole-4-carboxamide ribonucleoside, an AMPK agonist, significantly increased eNOS Ser1179 phosphorylation, NO bioactivity, and coimmunoprecipitation of eNOS with hsp90 in wild-type C57BL6 mice but not in AMPK-α1 knockout mice, suggesting that AMPK is required for metformin-enhanced eNOS activation in vivo. Finally, incubation of BAECs with clinically relevant concentrations of metformin dramatically attenuated high-glucose (30 mmol/l)–induced reduction in the association of hsp90 with eNOS, which resulted in increased NO bioactivity with a reduction in overexpression of adhesion molecules and endothelial apoptosis caused by high-glucose exposure. Taken together, our results indicate that metformin might improve vascular endothelial functions in diabetes by increasing AMPK-dependent, hsp90-mediated eNOS activation.