Assessment of antibacterial properties and the active ingredient of plant extracts and its effect on the performance of crucian carp (Carassius auratus gibelio var. E'erqisi, Bloch).

BACKGROUND: In this study, the antibacterial properties and active ingredient of plant extracts and its effect on the performance of crucian carp (Carassius auratus gibelio var. E'erqisi, Bloch) were assessed. RESULTS: The transmission electron microscopy and flow cytometric analysis showed that the antibacterial activity of plant extracts is due to the disruption of the cell membrane and the leakage of cytoplasmic contents. The UPLC-MS/MS analysis showed that the contents of gallic acid, (-)-epigallocatechin, (+)-catechin, (-)-epigallocatechin gallate, (-)-epicatechin gallate, aloe-emodin, rhein, emodin, chrysophanol, and physcion, were 5.27%, 3.30%, 1.08%, 19.32%, 5.46%, 0.23%, 0.56%, 1.28%, 0.75% and 0.39% in plant extracts, respectively. Results of feeding experiment showed that feeding crucian carp with 1.0% and 2.0% plant extracts significantly enhanced specific growth rate, serum total protein, lysozyme, catalase and superoxide dismutase activities, and decreased the feed conversion rate, malondialdehyde contents and the mortality rate (P < 0.05). CONCLUSION: It can be concluded that plant extracts added to fish feed can act as natural antimicrobial and immunostimulants to prevent pathogenic infection, enhance immune response, and promote growth of the fish.

Deworming drugs for soil-transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin and school performance.

BACKGROUND: The World Health Organization (WHO) recommends treating all school children at regular intervals with deworming drugs in areas where helminth infection is common. The WHO state this will improve nutritional status, haemoglobin, and cognition and thus will improve health, intellect, and school attendance. Consequently, it is claimed that school performance will improve, child mortality will decline, and economic productivity will increase. Given the important health and societal benefits attributed to this intervention, we sought to determine whether they are based on reliable evidence. OBJECTIVES: To summarize the effects of giving deworming drugs to children to treat soil-transmitted intestinal worms (nematode geohelminths) on weight, haemoglobin, and cognition; and the evidence of impact on physical well being, school attendance, school performance, and mortality. SEARCH METHODS: In February 2012, we searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, EMBASE, LILACS, mRCT, and reference lists, and registers of ongoing and completed trials. SELECTION CRITERIA: We selected randomized controlled trials (RCTs) and quasi-RCTs comparing deworming drugs for geohelminth worms with placebo or no treatment in children aged 16 years or less, reporting on weight, haemoglobin, and formal test of intellectual development. In cluster-RCTs treating communities or schools, we also sought data on school attendance, school performance, and mortality. We included trials that included health education with deworming. DATA COLLECTION AND ANALYSIS: At least two authors independently assessed the trials, evaluated risk of bias, and extracted data. Continuous data were analysed using the mean difference (MD) with 95% confidence intervals (CI). Where data were missing, we contacted trial authors. We used GRADE to assess evidence quality, and this is reflected in the wording we used: high quality ("deworming improves...."); moderate quality ("deworming probably improves..."); low quality ("deworming may improve...."); and very low quality ("we don't know if deworming improves...."). MAIN RESULTS: We identified 42 trials, including eight cluster trials, that met the inclusion criteria. Excluding one trial where data are awaited, the 41 trials include 65,168 participants.Screening then treatingFor children known to be infected with worms (by screening), a single dose of deworming drugs may increase weight (0.58 kg, 95% CI 0.40 to 0.76, three trials, 139 participants; low quality evidence) and may increase haemoglobin (0.37 g/dL, 95% CI 0.1 to 0.64, two trials, 108 participants; low quality evidence), but we do not know if there is an effect on cognitive functioning (two trials, very low quality evidence).Single dose deworming for all childrenIn trials treating all children, a single dose of deworming drugs gave mixed effects on weight, with no effects evident in seven trials, but large effects in two (nine trials, 3058 participants, very low quality evidence). The two trials with a positive effect were from the same very high prevalence setting and may not be easily generalised elsewhere. Single dose deworming probably made little or no effect on haemoglobin (mean difference (MD) 0.06 g/dL, 95% CI -0.06 to 0.17, three trials, 1005 participants; moderate evidence), and may have little or no effect on cognition (two trials, low quality evidence).Mulitple dose deworming for all childrenOver the first year of follow up, multiple doses of deworming drugs given to all children may have little or no effect on weight (MD 0.06 kg, 95% CI -0.17 to 0.30; seven trials, 2460 participants; low quality evidence); haemoglobin, (mean 0.01 g/dL lower; 95% CI 0.14 lower to 0.13 higher; four trials, 807 participants; low quality evidence); cognition (three trials, 30,571 participants, low quality evidence); or school attendance (4% higher attendance; 95% CI -6 to 14; two trials, 30,243 participants; low quality evidence);For time periods beyond a year, there were five trials with weight measures. One cluster-RCT of 3712 children in a low prevalence area showed a large effect (average gain of 0.98 kg), whilst the other four trials did not show an effect, including a cluster-RCT of 27,995 children in a moderate prevalence area (five trials, 37,306 participants; low quality evidence). For height, we are uncertain whether there is an effect of deworming (-0.26 cm; 95% CI -0.84 to 0.31, three trials, 6652 participants; very low quality evidence). Deworming may have little or no effect on haemoglobin (0.00 g/dL, 95%CI -0.08 to 0.08, two trials, 1365 participants, low quality evidence); cognition (two trials, 3720 participants; moderate quality evidence). For school attendance, we are uncertain if there is an effect (mean attendance 5% higher, 95% CI -0.5 to 10.5, approximately 20,000 participants, very low quality evidence).Stratified analysis to seek subgroup effects into low, medium and high helminth endemicity areas did not demonstrate any pattern of effect. In a sensitivity analysis that only included trials with adequate allocation concealment, we detected no significant effects for any primary outcomes.One million children were randomized in a deworming trial from India with mortality as the primary outcome. This was completed in 2005 but the authors have not published the results. AUTHORS' CONCLUSIONS: Screening children for intestinal helminths and then treating infected children appears promising, but the evidence base is small. Routine deworming drugs given to school children has been more extensively investigated, and has not shown benefit on weight in most studies, except for substantial weight changes in three trials conducted 15 years ago or more. Two of these trials were carried out in the same high prevalence setting. For haemoglobin and cognition, community deworming seems to have little or no effect, and the evidence in relation to school attendance, and school performance is generally poor, with no obvious or consistent effect. Our interpretation of this data is that it is probably misleading to justify contemporary deworming programmes based on evidence of consistent benefit on nutrition, haemoglobin, school attendance or school performance as there is simply insufficient reliable information to know whether this is so.

Deworming drugs for soil-transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin and school performance.

BACKGROUND: The World Health Organization (WHO) recommends treating all school children at regular intervals with deworming drugs in areas where helminth infection is common. The WHO state this will improve nutritional status, haemoglobin, and cognition and thus will improve health, intellect, and school attendance. Consequently, it is claimed that school performance will improve, child mortality will decline, and economic productivity will increase. Given the important health and societal benefits attributed to this intervention, we sought to determine whether they are based on reliable evidence. OBJECTIVES: To summarize the effects of giving deworming drugs to children to treat soil-transmitted intestinal worms (nematode geohelminths) on weight, haemoglobin, and cognition; and the evidence of impact on physical well being, school attendance, school performance, and mortality. SEARCH METHODS: In February 2012, we searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, EMBASE, LILACS, mRCT, and reference lists, and registers of ongoing and completed trials. SELECTION CRITERIA: We selected randomized controlled trials (RCTs) and quasi-RCTs comparing deworming drugs for geohelminth worms with placebo or no treatment in children aged 16 years or less, reporting on weight, haemoglobin, and formal test of intellectual development. In cluster-RCTs treating communities or schools, we also sought data on school attendance, school performance, and mortality. We included trials that included health education with deworming. DATA COLLECTION AND ANALYSIS: At least two authors independently assessed the trials, evaluated risk of bias, and extracted data. Continuous data were analysed using the mean difference (MD) with 95% confidence intervals (CI). Where data were missing, we contacted trial authors. We used GRADE to assess evidence quality, and this is reflected in the wording we used: high quality ("deworming improves...."); moderate quality ("deworming probably improves..."); low quality ("deworming may improve...."); and very low quality ("we don't know if deworming improves...."). MAIN RESULTS: We identified 42 trials, including eight cluster trials, that met the inclusion criteria. Excluding one trial where data are awaited, the 41 trials include 65,168 participants.For programmes that treat only children detected as infected (by screening), a single dose of deworming drugs probably increased weight (0.58 kg, 95% CI 0.40 to 0.76, three trials, 139 participants; moderate quality evidence) and may have increased haemoglobin (0.37 g/dL, 95% CI 0.1 to 0.64, two trials, 108 participants; low quality evidence), but we do not know if there is an effect on cognitive functioning (two trials, very low quality evidence).For a single dose of deworming drugs given to all children in endemic areas, there were mixed effects on weight, with no effects evident in seven trials, but large effects in two. Overall our analysis indicated that we are uncertain whether there was an effect on weight (nine trials, 3058 participants; very low quality evidence). For haemoglobin, deworming made little or no difference (0.02 g/dL, 95% CI -0.05 to 0.09, four trials, 1992 participants; low quality evidence), and we don't know if it improves cognition (one trial, very low quality evidence).For multiple doses of deworming drugs with follow up for up to one year given to all children in endemic areas, we are uncertain if there is an effect on weight (0.06 kg, 95% CI -0.17 to 0.30; seven trials, 2460 participants; very low quality evidence); cognition (three trials, very low quality evidence); or school attendance (4% higher attendance; 95% CI -6 to 14; two trials, 75 clusters and 143 individually randomized participants, very low quality evidence). For haemoglobin, the intervention may have little or no effect (mean 0.01 g/dL lower; 95% CI 0.14 lower to 0.13 higher; four trials, 807 participants; low quality evidence).For multiple doses of deworming drugs with follow up beyond one year given to all children in endemic areas there were five trials with weight measures. One cluster-RCT of 3712 children in a low prevalence area showed a large effect (average gain of 0.98kg), whilst the other four trials did not show an effect, including a cluster-RCT of 27,995 children in a moderate prevalence area. Overall, we are uncertain if there is an effect for weight (five trials, 302 clusters and 1045 individually randomized participants; very low quality evidence). For other outcomes, we are uncertain whether deworming affects height (-0.26 cm; 95%CI -0.84 to 0.31, three trials, 1219 participants); haemoglobin (0.02 g/dL, 95%CI 0.3 to 0.27, two trials, 1365 participants); cognition (two trials), or school attendance (mean attendance 5% higher, 95% CI -0.5 to 10.5, one trial, 50 clusters).Stratified analysis to seek subgroup effects into low, medium and high helminth endemicity areas did not demonstrate any pattern of effect. We did not detect any significant effects for any primary outcomes in a sensitivity analysis only including trials with adequate allocation concealment.One million children were randomized in a deworming trial from India with mortality as the primary outcome. This was completed in 2005 but the authors have not published the results. AUTHORS' CONCLUSIONS: Screening children for intestinal helminths and then treating infected children appears promising, but the evidence base is small. Routine deworming drugs given to school children has been more extensively investigated, and has not shown benefit on weight in most studies, except for substantial weight changes in three trials conducted 15 years ago or more. Two of these trials were carried out in the same high prevalence setting. For haemoglobin, community deworming seems to have little or no effect, and the evidence in relation to cognition, school attendance, and school performance is generally poor, with no obvious or consistent effect. Our interpretation of this data is that it is probably misleading to justify contemporary deworming programmes based on evidence of consistent benefit on nutrition, haemoglobin, school attendance or school performance as there is simply insufficient reliable information to know whether this is so.

Diagnostic approach and management of cow's-milk protein allergy in infants and children: ESPGHAN GI Committee practical guidelines.

OBJECTIVES: This guideline provides recommendations for the diagnosis and management of suspected cow's-milk protein allergy (CMPA) in Europe. It presents a practical approach with a diagnostic algorithm and is based on recently published evidence-based guidelines on CMPA. DIAGNOSIS: If CMPA is suspected by history and examination, then strict allergen avoidance is initiated. In certain circumstances (eg, a clear history of immediate symptoms, a life-threatening reaction with a positive test for CMP-specific IgE), the diagnosis can be made without a milk challenge. In all other circumstances, a controlled oral food challenge (open or blind) under medical supervision is required to confirm or exclude the diagnosis of CMPA. TREATMENT: In breast-fed infants, the mother should start a strict CMP-free diet. Non-breast-fed infants with confirmed CMPA should receive an extensively hydrolyzed protein-based formula with proven efficacy in appropriate clinical trials; amino acids-based formulae are reserved for certain situations. Soy protein formula, if tolerated, is an option beyond 6 months of age. Nutritional counseling and regular monitoring of growth are mandatory in all age groups requiring CMP exclusion. REEVALUATION: Patients should be reevaluated every 6 to 12 months to assess whether they have developed tolerance to CMP. This is achieved in >75% by 3 years of age and >90% by 6 years of age. Inappropriate or overly long dietary eliminations should be avoided. Such restrictions may impair the quality of life of both child and family, induce improper growth, and incur unnecessary health care costs.

Toxicity assessment of zebrafish following exposure to CdTe QDs.

CdTe quantum dots (QDs) are nanocrystals of unique composition and properties that have found many new commercial applications; therefore, their potential toxicity to aquatic organisms has become a hot research topic. The lab study was performed to determine the developmental and behavioral toxicities to zebrafish under continuous exposure to low concentrations of CdTe QDs (1-400 nM) coated with thioglycolic acid (TGA). The results show: (1) the 120 h LC(50) of 185.9 nM, (2) the lower hatch rate and body length, more malformations, and less heart beat and swimming speed of the exposed zebrafish, (3) the brief burst and a higher basal swimming rate of the exposed zebrafish larvae during a rapid transition from light-to-dark, and (4) the vascular hyperplasia, vascular bifurcation, vascular crossing and turbulence of the exposed FLI-1 transgenic zebrafish larvae.

[Attention deficit disorder and hyperactivity: does the treatment affect the statural growth?]. / Hiperatividade e déficit de atenção: o tratamento prejudica o crescimento estatural?

The current study evaluated the influence of stimulant drugs used for attention deficit and hyperactivity (ADH) on statural growth. The authors conducted a literature review collecting published articles on attention deficit hyperactivity disorder and its relationship with short stature. The source of information was the PubMed database where the following terms were researched: "Growth and Methylphenidate"/"Attention deficit and hyperactivity versus short stature"/"Methylphenidate and growth disorders". ADH are difficult clinical situations that interfere with the patient's well-being and social and school performance. Once the diagnosis is attained stimulant medications such as methylphenidate have a key role in the treatment but there are concerns regarding their interference in growth and weight gain. We reviewed many publications regarding these side effects and there is no consensus on them; however, even when they happen to occur their intensity is not sufficient to preclude the use of the medication. We have to take into consideration the cost/benefit relationship, remembering that improvement in school and social performance are very welcome to the child and family. Careful monitoring of the growth chart can detect worsening of growth and its intensity will determine if the drug shall or shall not be interrupted.

Hiperatividade e déficit de atenção: o tratamento prejudica o crescimento estatural? / Attention deficit disorder and hyperactivity: does the treatment affect the statural growth?

O presente estudo avaliou a influência de drogas estimulantes usadas no déficit de atenção e hiperatividade no crescimento estatural. Os autores procederam a uma revisão de literatura coletando artigos publicados sobre déficit de atenção e hiperatividade e sua relação com a baixa estatura. A fonte consultada foi o PubMed e o tópico levantado foi "Crescimento e Metilfenidato"/"Déficit de atenção e hiperatividade versus baixa estatura"/"Metilfenidato e distúrbios de crescimento". Os transtornos de atenção e hiperatividade constituem-se em situações clínicas difíceis, por interferir no bem-estar da criança e no seu relacionamento social, com prejuízos de seu desenvolvimento escolar. Uma vez feito o diagnóstico, as medicações estimulantes como o metilfenidato têm papel primordial no tratamento, mas muito se teme com relação a certos efeitos colaterais, particularmente a perda de peso e a perda estatural. Revisou-se uma série de publicações a respeito e pôde-se verificar que não há consenso sobre tais efeitos colaterais, mas que, mesmo quando ocorrem, não são suficientemente intensos para impedir o tratamento. Um julgamento da relação custo-benefício da medicação é sempre apropriado, mas os benefícios obtidos com a medicação e com a melhora do rendimento escolar e das relações sociais da criança não devem ser esquecidos. Uma cuidadosa monitorização da curva pondoestatural permite que o médico vigie com segurança o tratamento prescrito e possa tomar decisões se julgar que o prejuízo estatural compromete o bem-estar do paciente.

The current study evaluated the influence of stimulant drugs used for attention deficit and hyperactivity (ADH) on statural growth. The authors conducted a literature review collecting published articles on attention deficit hyperactivity disorder and its relationship with short stature. The source of information was the PubMed database where the following terms were researched: "Growth and Methylphenidate"/"Attention deficit and hyperactivity versus short stature"/"Methylphenidate and growth disorders". ADH are difficult clinical situations that interfere with the patient's well-being and social and school performance. Once the diagnosis is attained stimulant medications such as methylphenidate have a key role in the treatment but there are concerns regarding their interference in growth and weight gain. We reviewed many publications regarding these side effects and there is no consensus on them; however, even when they happen to occur their intensity is not sufficient to preclude the use of the medication. We have to take into consideration the cost/benefit relationship, remembering that improvement in school and social performance are very welcome to the child and family. Careful monitoring of the growth chart can detect worsening of growth and its intensity will determine if the drug shall or shall not be interrupted.

Effects of budesonide inhalation on energy expenditure, somatic growth and salivary cortisol levels in preterm infants with chronic lung disease.

BACKGROUND: We hypothesized that the use of inhaled budesonide (BUD) would alter somatic growth by increasing energy expenditure (EE) in premature infants with chronic lung disease (CLD). METHODS: A prospective study was conducted of the effect of BUD on EE, growth and salivary cortisol excretion in infants with CLD who required supplemental oxygen and were treated with inhaled BUD for 4 weeks according the severity of their CLD, or without BUD treatment. Infants were compared with a healthy control group matched for gestational age. EE, anthropometric measures and salivary cortisol levels were examined before, during and after BUD treatment. RESULTS: A total of 30 spontaneously breathing premature infants were enrolled in the study. EE in CLD (BUD) and CLD (no BUD) patients were greater than EE in healthy preterm infants (p < 0.01) at the study time points. Growth did not differ between the groups. Salivary cortisol levels of treated infants were significantly lower when compared with the levels of nontreated infants. CONCLUSION: The administration of inhaled BUD in preterm infants with CLD was associated with an increase in EE, a suppression of endogenous cortisol production and with no effect on duration of supplemental oxygen, but did not compromise their somatic growth.

Mecasermin: new drug. Insufficient improvement in statural growth.

(1) Human insulin-like growth factor type 1 (IGF-1) is the main effector of growth hormone action. Primary IGF-1 deficiency is a rare disease, mainly resulting in very short stature; (2) Mecasermin is a recombinant IGF-1 marketed for this indication as a twice daily subcutaneous injection; (3) Clinical evaluation is mainly based on a non-comparative follow-up study of 76 children with an average age of 7 years, some of whom were treated for 8 years. The mean height at treatment initiation was 6.7 standard deviations below normal. Eight years later, it was 5.2 standard deviations below normal, i.e. their growth failure remained very severe; (4) The main short-term adverse effects of mecasermin are hypoglycaemia, headache and intracranial hypertension. Nearly one in 5 children developed tonsillar hypertrophy, resulting in otitis and hypoacusis; (5) Animal studies showed hypertrophy of other organs (kidneys, spleen and heart) as well as carcinogenic effects. The risk in humans is unknown; (6) The mecasermin packaging is not well-adapted (a multidose vial designed to be punctured several times), and is a potential source of contamination and errors. Prefilled pens or syringes would be easier to use; (7) In practice, the limited clinical benefits of mecasermin do not justify exposure to its potential risks.

Effects of micronutrients on growth of children under 5 y of age: meta-analyses of single and multiple nutrient interventions.

BACKGROUND: Micronutrient interventions have received much attention as a cost-effective and promising strategy to improve child health, but their roles in improving child growth remain unclear. OBJECTIVE: Meta-analyses of randomized controlled trials were conducted to evaluate the effect of micronutrient interventions on the growth of children aged <5 y old. DESIGN: Eligible studies were identified by PubMed database searches and other methods. Weighted mean effect sizes and 95% CIs were calculated for changes in height, weight, and weight-for-height z scores (WHZ) by using random-effect models. Tests for publication bias were done by using funnel plots, heterogeneity, and stratified analyses by predefined characteristics. RESULTS: Interventions including iron (n = 27) or vitamin A (n = 17) only had no significant effects on growth. Interventions including zinc only (n = 43) had a small positive effect (effect size = 0.06; 95% CI: 0.006, 0.11) on change in WHZ but no significant effect on height or weight gain. Multiple micronutrient interventions (n = 20) improved linear growth (0.09; 95% CI: 0.008, 0.17). CONCLUSIONS: Our findings confirm earlier results of no benefits for interventions including iron and vitamin A only but differ from the earlier meta-analysis that found improvements in linear growth for zinc only interventions. This may be due to the improved nutritional status of children in the more recent studies. Multiple micronutrient interventions improve linear growth, but the benefits are small. Other strategies are needed to prevent stunting.

Integrative assessment of coastal pollution in a Ría coastal system (Galicia, NW Spain): correspondence between sediment chemistry and toxicity.

Elutriate embryo-larval bioassays with sea-urchins (Paracentrotus lividus) and ascidians (Ciona intestinalis) were conducted concurrently with trace metal analyses as part of an integrative assessment of sediment pollution at Ría de Pontevedra (Galicia, NW Spain). High metal contents in sediments were found in localised areas from the inner part of the estuary indicating a clear anthropogenic influence. In particular, very high Cu, Zn and Pb levels were found at sites P2 and P3, which were also the most toxic to the embryo-larval bioassays. Sediment quality guidelines were used to help in the ecological interpretation of sediment chemistry data and to identify pollutants of concern. Cu and Zn in P3 were consistently above the effects range median (ERM) values, which seem to be good predictors of toxicity to sea-urchin and ascidian embryos. A toxic unit approach, based on published EC(50) values and metal levels in elutriates, was used to assess the harmful ecological effects associated to sediment chemistry. Toxicity detected in P3 may be explained on the basis of the toxic unit model; however, the high toxicity detected at P2 may be attributable not only to the metals quantified in the analyses but also to unmeasured organic pollutants. Multidimensional scaling applied independently to the toxicology and chemistry data resulted in a good agreement between both types of configurations. Moreover, the Mantel test revealed a significant correlation (r(M)=0.481; p=0.019) between metal concentrations and toxicity data profiles, supporting the correspondence between configurations.

Exposure and effects assessment of resident mink (Mustela vison) exposed to polychlorinated dibenzofurans and other dioxin-like compounds in the Tittabawassee River basin, Midland, Michigan, USA.

Historically, sediments and floodplain soils of the Tittabawassee River (TR; MI, USA) have been contaminated with polychlorinated dibenzofurans (PCDFs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated biphenyls (PCBs). Median concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs) based on 2006 World Health Organization tetrachlorodibenzo-p-dioxin toxic equivalency factors (TEFs) in the diet of mink (Mustela vison) ranged from 6.8 x 10(-1) ng TEQ/kg wet weight upstream of the primary source of PCDF to 3.1 x 10(1) ng TEQ/kg wet weight downstream. Estimates of toxicity reference values (TRVs) derived from laboratory studies with individual PCDDs/PCDFs and PCB congeners or mixtures of those congeners, as well as application of TEFs, were compared to site-specific measures of mink exposure. Hazard quotients based on exposures expressed as concentrations of TEQs in the 95th percentile of the mink diet or liver and the no-observable-adverse-effect TRVs were determined to be 1.7 and 8.6, respectively. The resident mink survey, however, including number of mink present, morphological measures, sex ratios, population age structure, and gross and histological tissue examination, indicated no observable adverse effects. This resulted for multiple reasons: First, the exposure estimate was conservative, and second, the predominantly PCDF congener mixture present in the TR appeared to be less potent than predicted from TEQs based on dose-response comparisons. Given this, there appears to be great uncertainty in comparing the measured concentrations of TEQs at this site to TRVs derived from different congeners or congener mixtures. Based on the lack of negative outcomes for any measurement endpoints examined, including jaw lesions, a sentinel indicator of possible adverse effects, and direct measures of effects on individual mink and their population, it was concluded that current concentrations of PCDDs/PCDFs were not causing adverse effects on resident mink of the TR.

Cost-effective experimental design to support modeling of concentration-response functions.

Modeling concentration-response function became extremely popular in ecotoxicology during the last decade. Indeed, modeling allows determining the total response pattern of a given substance. However, reliable modeling is consuming in term of data, which is in contradiction with the current trend in ecotoxicology, which aims to reduce, for cost and ethical reasons, the number of data produced during an experiment. It is therefore crucial to determine experimental design in a cost-effective manner. In this paper, we propose to use the theory of locally D-optimal designs to determine the set of concentrations to be tested so that the parameters of the concentration-response function can be estimated with high precision. We illustrated this approach by determining the locally D-optimal designs to estimate the toxicity of the herbicide dinoseb on daphnids and algae. The results show that the number of concentrations to be tested is often equal to the number of parameters and often related to the their meaning, i.e. they are located close to the parameters. Furthermore, the results show that the locally D-optimal design often has the minimal number of support points and is not much sensitive to small changes in nominal values of the parameters. In order to reduce the experimental cost and the use of test organisms, especially in case of long-term studies, reliable nominal values may therefore be fixed based on prior knowledge and literature research instead of on preliminary experiments.

Assessment of the long-term safety of inhaled ciclesonide on growth in children with asthma.

OBJECTIVE: To assess the effects of the new inhaled corticosteroid ciclesonide on growth in children with asthma. METHODS: We performed a multicenter, randomized, double-blind, placebo-controlled study to assess the effects of inhaled ciclesonide on growth in children with mild, persistent asthma. After a 6-month run-in period, 661 prepubertal children who were aged 5.0 to 8.5 years were randomly assigned to once-daily morning treatment for 1 year with ciclesonide 40 or 160 microg (ex-actuator) or placebo, followed by a 2-month follow-up period. The primary end point was the linear growth velocity (linear regression estimate) over the double-blind treatment period. Growth was recorded as the median of 4 stadiometer measurements. Adverse events and 10-hour overnight and 24-hour urinary free cortisol levels were also assessed. RESULTS: Mean linear growth velocity during run-in was comparable between groups: 160 microg, 6.20 cm/year; 40 microg, 6.59 cm/year; placebo, 6.49 cm/year. Mean differences from placebo (5.75 cm/year) in growth velocity over the double-blind treatment period were -0.02 cm/year for ciclesonide 40 microg and -0.15 cm/year for ciclesonide 160 microg. Both ciclesonide treatments were noninferior to placebo with respect to growth velocity. The overall incidence of adverse events was comparable between groups, and no significant changes in 10-hour overnight or 24-hour urinary free cortisol levels were noted between groups during the double-blind treatment period. CONCLUSIONS: Ciclesonide demonstrated no detectable effect on childhood growth velocity, even at the highest dosage, which may ease concerns about systemic adverse events.

Effects of bovine serum concentrate, with or without supplemental micronutrients, on the growth, morbidity, and micronutrient status of young children in a low-income, peri-urban Guatemalan community.

OBJECTIVE: To determine the effects of dietary supplements containing bovine serum concentrate (BSC, a source of immunoglobulins) and/or multiple micronutrients (MMN) on children's growth velocity, rates of common infections, and MN status. DESIGN: Randomized, controlled, community-based intervention trial. SETTING: Low-income, peri-urban Guatemalan community. SUBJECTS: Children aged 6-7 months initially. INTERVENTIONS: Children received one of four maize-based dietary supplements daily for 8 months, containing: (1) BSC, (2) whey protein concentrate (WPC, control group), (3) WPC+MMN, or (4) BSC+MMN. RESULTS: There were no significant differences in growth or rates of morbidity by treatment group. Children who received MMN had lower rates of anemia and (in the group that received WPC+MMN) less of a decline in serum ferritin than those who did not, but there were no differences in other biochemical indicators of MN status by treatment group. CONCLUSIONS: MMN supplementation reduced anemia and iron deficiency in this population, but the MMN content and source of protein in the supplements did not affect other indicators of MN status, growth or morbidity.

Recombinant rat and mouse growth hormones: risk assessment of carcinogenic potential in 2-year bioassays in rats and mice.

Recombinant rat growth hormone (rrGH) and recombinant mouse growth hormone (rmGH) were developed to evaluate the potential carcinogenicity of each biologically active growth hormone (GH) as assessed in the respective species. Biological activities of rrGH and rmGH were demonstrated by showing an increase in body weight gain and serum levels of insulin-like growth factor-1 (IGF-1) in hypophysectomized rats receiving daily sc injections for 6 days. With the exception of pharmacologically mediated weight gain, rrGH and rmGH had no adverse effects in 5-week oral toxicity studies and no production of anti-recombinant GH antibodies. The high doses selected for the carcinogenicity studies provided systemic exposures of GH up to approximately 10-fold over basal levels. In the 105-week mouse carcinogenicity study, daily sc injections of rmGH at 0.1, 0.2, or 0.5 mg/kg/day were well tolerated and had no effects on survival or incidence of tumors. In the 106-week rat carcinogenicity study, daily sc injections of rrGH at 0.2, 0.4, or 0.8 mg/kg/day had a favorable effect on longevity in female rats administered 0.4 or 0.8 mg/kg/day, an increased weight gain in females and males, and no increase in the incidence of tumors. The absence of carcinogenic effects of recombinant GH administered daily for 2 years to rodents was consistent with publications of clinical experience, indicating a lack of convincing evidence for an increased risk of cancer in children receiving human recombinant GH replacement therapy.

Nutritional assessment and serum zinc and copper concentration among children with acute lymphocytic leukemia: a longitudinal study

CONTEXT AND OBJECTIVE: When undergoing chemotherapy and/or radiotherapy, children with acute lymphocytic leukemia may present important nutritional disorders because of the gastrointestinal toxicity of most chemotherapy agents or the effects of radiation on the organism. These patients may also present changes in their serum concentrations of trace elements such as zinc and copper. The present study aimed to follow anthropometric parameters and serum levels of zinc and copper in a group of children under treatment for acute lymphocytic leukemia. DESIGN AND SETTING: Longitudinal study, at the Pediatric Section of Hospital das Clínicas, Ribeirão Preto, Brazil. METHODS: Forty-five children with acute lymphocytic leukemia were studied. Anthropometric parameters such as weight and height and the daily intakes and serum levels of copper and zinc were recorded at diagnosis and during the treatment. RESULTS: During the initial phase of the treatment, there was an increase in energy intake accompanied by weight gain. However, during the later phases of treatment there was a reduction in energy intake with accompanying weight loss. Decreased growth rate during treatment was more pronounced in children with high-risk acute lymphocytic leukemia, probably due to radiation therapy. Serum zinc levels remained basically unaltered during the treatment, whereas copper levels decreased dramatically with the beginning of treatment. CONCLUSIONS: The treatment given to children with acute lymphocytic leukemia has an important effect on their linear growth rate and nutritional status, and also on their serum copper levels.

CONTEXTO E OBJETIVO: Crianças portadoras de leucemia linfóide aguda quando em tratamento quimioterápico e/ou radioterápico podem apresentar comprometimento do estado nutricional devido aos efeitos tóxicos a nível gastrointestinal dos agentes quimioterápicos ou aos efeitos da radioterapia sobre o organismo. Esses pacientes também podem apresentar alterações nas concentrações séricas de zinco e cobre. O objetivo foi acompanhar os parâmetros antropométricos e os níveis séricos de zinco e cobre de crianças em tratamento para leucemia linfóide aguda. TIPO DE ESTUDO E LOCAL: Estudo longitudinal, realizado no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, São Paulo, Brasil, que envolveu 45 crianças do Serviço de Oncologia pediátrica, portadoras de leucemia linfóide aguda. MÉTODOS: Medidas antropométricas como peso e altura, medidas de consumo alimentar, assim como níveis séricos de zinco e cobre foram avaliados ao diagnóstico e durante o tratamento. RESULTADOS: No início do tratamento, houve aumento na ingestão calórica, acompanhada de ganho de peso, no entanto, nas fases seguintes ao tratamento houve redução na ingestão alimentar, resultando em perda de peso. Diminuição na velocidade de crescimento foi notada nas crianças com leucemia linfóide aguda de alto risco que foram submetidas a radioterapia. Os níveis séricos de zinco não sofreram alterações durante o tratamento, já os níveis séricos de cobre tiveram importante diminuição em relação ao início do tratamento. CONCLUSÕES: Pudemos observar alterações no estado nutricional, assim como alterações nas concentrações séricas de micronutrientes durante o tratamento para leucemia linfóide aguda.

A multilevel approach to predict toxicity in copepod populations: assessment of growth, genetics, and population structure.

One of the goals of environmental risk assessment (ERA) is to understand effects of toxicant exposure on individual organisms and populations. We hypothesized that toxicant exposure can reduce genetic diversity and alter genotype composition, which may ultimately lead to a reduction in the average fitness of the exposed population. To test this hypothesis, we exposed a copepod, Nitocra psammophila, to a toxic reference compound and assayed resulting alterations in genetic structure, i.e. expected heterozygosity and percent polymorphic loci, as well as other population- and fitness-related measures, i.e. population abundance, demographic structure and juvenile growth. The copepods were exposed to 0.11-1.1 microg of the pentabromo-substituted diphenyl ether (BDE-47) mg(-1) freeze-dried algae for 24 days (i.e. >1 generation). There was no significant decline in total population abundance. However, there were significant alterations in population structure, manifested as diminished proportion of nauplii and increased proportion of copepodites. In addition, individual RNA content in copepodites decreased significantly in exposed individuals, indicating declined growth. Finally, in the exposed populations, heterozygosity was lower and genotype composition was altered compared to the controls. These results therefore confirm the hypothesized reduction in overall genetic variability resulting from toxicant exposure. Multilevel approaches, such as the one used in the present study, may help unravel subtle effects on the population level, thus increasing the predictive capacity of future ERA.