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Oestrogens are key regulators in sexual differentiation and development in higher vertebrates. P450 aromatase (P450arom) is the steroidogenic enzyme responsible for the synthesis of oestrogens from aromatisable androgens. Effects of endocrine disrupting chemicals on steroidogenic enzyme gene expression have received little attention so far, yet it is potentially a major pathway for sexual disruption. In this 14-day study the effects of exogenous 17β-oestradiol (E2) at environmentally relevant concentrations were assessed on gene expression of P450aromB in the gonad and brain of maturing male and female fathead minnows (FHM). Exposure to E2 resulted in an oestrogenic response as shown by a dose-dependent induction of plasma vitellogenin (VTG) in female and male fish and a dose-dependent inhibition of testis growth. There was an effect of exposure to E2 on P450aromB mRNA expression in the gonads; E2 up-regulated P450aromB mRNA expression in the testis and ovary in a dose-response manner after 14 days of exposure. In male brain, P450aromB mRNA concentrations were significantly reduced in fish exposed to 100 and 320 ng E2/l on day 4, but on day 14 were elevated in males exposed to both 32 and 100 ng E2/l. No effects of E2 on P450aromB mRNA expression occurred in the brain of females. The results of this study show that concentrations of E2 found in the environment can have disruptive effects on key steroidogenic enzyme pathways that control sexual development in fish. [Copyright &y& Elsevier]

P450 17α-hydroxylase,17,20-lyase (P450c17) is a key steroidogenic enzyme in the production of androgens and, therefore, is also indispensable for the production of oestrogens (that are produced from the aromatisation of androgens). In this study, P450c17 cDNA was cloned from the ovary of the fathead minnow (FHM) and its gene expression was examined in the gonads and brains of male and female FHM at different stages of gonadal development with a view to developing an understanding of its involvement in the reproductive physiology in this species. The FHM-P450c17 cDNA sequence cloned was 1812 bp in length, with an open reading frame of 1554 nucleotides encoding a protein of 518 amino acids. Amino acid identity of FHM-P450c17 with P450c17s in other animals was up to 81.8% in other teleosts (channel catfish), 62% in elasmobranches (spiny dogfish), 64% in birds (chicken), and up to 48.8% in mammals (human). FHM-P450c17 gene expression occurred in the ovary, testis, and also in the brain (both male and female) at all stages of sexual development studied. Expression in the brain was at least 30-fold lower than in the gonads, but consistent in all fish life stages studied. In the testis, FHM-P450c17 gene expression was negatively correlated with gonadal development, but there was no obvious association between P450c17 gene expression and sexual development in the ovary, or brain (in both males and females). The results from this study demonstrate the expression of P450c17 in the brain for the first time in fish. Enzymatic studies are now needed to investigate the possible role of P450c17 in neurosteroid production in teleosts. [Copyright &y& Elsevier]

We report the clinical and serological response of 72 children and adolescents after immunization with the 23-valent polysaccharide pneumococcal vaccine (PPV23). All had been diagnosed with recurrent upper respiratory tract infections and low antipneumococcal immunity. Forty-five (62%) of these patients had received PCV7, the 7-serotype pneumococcal conjugated vaccine (Prevnar7). After immunization with the polysaccharide vaccine, 69 (96%) patients, including 42 of the 45 who had previously been immunized with the conjugate vaccine, had a positive clinical response including 12 patients (17%) whose serological response to the polysaccharide vaccine was inadequate. Clinical and serological response to PPV23 was assessed at approximately 1, 3 and 6 months after immunization. Our study also confirmed that a small group of patients with recurrent upper respiratory tract infections are unable to develop a normal response to pneumococcal and other bacterial polysaccharides despite vaccination with the newer conjugated vaccines. This immunodeficiency has been named selective antibody deficiency with normal immunoglobulins or impaired polysaccharide responsiveness. These patients did well after administration of intravenous IgG.

Desmoid-type (aggressive) fibromatosis (desmoid tumor) is a soft tissue neoplasm that can occur in both children and adults. Although it is formally classified as an intermediate-grade neoplasm because of its propensity for locally invasive growth, it can lead to severe and life-threatening problems. Because metastases do not arise from desmoid tumor, therapeutic interventions have historically focused on surgery or radiation to achieve local tumor control. These approaches may be ineffective or impractical for some children. In those cases, systemic therapy with cytotoxic or noncytotoxic therapy has been used. Because of the relative rarity of this neoplasm in children, knowledge on the use of chemotherapy is based largely on anecdotal reports or retrospective series. Limited conclusions can be drawn, though, from these types of reports. In the last 10 years, two prospective phase II clinical trials of chemotherapy for children with desmoid tumor have been conducted in cooperative clinical trials centered in North America. We review the results of those clinical trials and suggest future directions for systematically approaching this disease to better define the role of chemotherapy for children with desmoid tumor.

Laboratory populations of freshwater Keeled rams horn snails (Planorbis carinatus Muller, 1774) were exposed as adults to measured concentrations of ibuprofen free base (CAS number 15687-27-1) for up to 21 d using methanol (0.1 mL/L) as a carrier solvent. Under flow-through conditions, the 48 and 72 h LC50 values were both 17.1mg/L (95% confidence intervals 5.9-72.3mg/L), while 21 d LOEC and NOEC values based on survival were >5.36 and 5.36 mg/L, respectively. Reproduction (in terms of hatching success) 21d LOEC and NOEC values were 5.36 and 2.43 mg/L, respectively. Growth (wet weight) was the most sensitive endpoint measured at 21 d, with LOEC and NOEC values of 2.43 and 1.02 mg/L, respectively. We found P. carinatus to be amenable to laboratory culture and this preliminary study suggests that this species may have further potential as a useful molluscan model in ecotoxicology.

It has been claimed that bisphenol A (BPA) induces superfeminization in the freshwater gastropod, Marisa cornuarietis. To explore the reproducibility of prior work, here we present results from a three-laboratory study, the objectives of which were to determine the mean and variability in test endpoints (i.e., adult fecundity, egg hatchability, and juvenile growth) under baseline conditions and to identify the sources of variability. A major source of variability for all of the measured endpoints was due to differences within and among individuals. With few exceptions, variability among laboratories and among replicate tanks within laboratories contributed little to the observed variability in endpoints. The results highlight the importance of obtaining basic knowledge of husbandry requirements and baseline information on life-history traits of potential test species prior to designing toxicity test protocols. Understanding of the levels and sources of endpoint variability is essential so that statistically robust and ecologically relevant tests of chemicals can be conducted.

The present experiments are part of a larger study designed to investigate the influence of husbandry parameters on the life history of the ramshorn snail, Marisa cornuarietis, in order to identify suitable husbandry conditions for maintaining multi-generation populations in the laboratory for use in ecotoxicological testing. In this paper we focus on the effects of a combination of food types and feeding frequencies (i.e., the frequency with which the snails were offered food) on juvenile growth and survival at different temperatures. Offspring produced in the laboratory by wild specimens of M. cornuarietis, from Puerto Rico, were used to test the effects of three types of food (lettuce, alginate with fish food, alginate with snail mix) fed at three frequencies (given ad libitum on 4/4, 2/4, or 1/4 d) on juvenile survival and growth. The 4-d feeding regimens were repeated four times, giving a total of 16 d for the experiments. The experiments were conducted at two temperatures (22 degrees and 25 degrees C) under a 12 h light:12 h dark photoperiod. Juvenile growth rates increased with increasing feeding frequency for all food types. The most rapid growth rates occurred in the high-frequency lettuce treatments and the slowest growth rates in the low-frequency lettuce and alginate with snail mix treatments. Juvenile snails grew faster at 25 degrees than at 22 degrees C, and mortality was about twice as high at the lower temperature. Growth rates were used to provide a rough estimate of time to maturity, which was determined to take about twice as long at 22 degrees than at 25 degrees C. The results showed that lettuce is the best food if supplied in abundance, but effects on growth are very dependent on feeding frequency and temperature. We conclude that 25 degrees C is a more appropriate temperature for maintaining populations than 22 degrees C, that lettuce provides a suitable food source, and that food should be supplied continuously for husbandry and toxicity testing of populations of M. cornuarietis.

These experiments are part of a larger study designed to investigate the influence of husbandry parameters on the life history of the apple snail, Marisa cornuarietis. The overall objective of the program is to identify suitable husbandry conditions for maintaining multi-generation populations of this species in the laboratory for use in ecotoxicological testing. In this article, we focus on the effects of photoperiod, temperature, and population density on adult fecundity and juvenile growth. Increasing photoperiod from 12 to 16 h of light per day had no effect on adult fecundity or egg hatching and relatively minor effects on juvenile growth and development. Rearing snails at temperatures between 22 degrees C and 28 degrees C did not influence the rates of egg production or egg clutch size. However, the rates of growth and development (of eggs and juveniles) increased with increasing temperature in this range, and when temperatures were reduced to 22 degrees C egg-hatching success was impaired. Juvenile growth and development were more sensitive to rearing density than adult fecundity traits. On the basis of the present results, we conclude that rearing individuals of M. cornuarietis at a temperature of 25 degrees C, a photoperiod of 12L:12D, and a density of <0.8 snails L(-1) (with lower densities for juvenile snails) should provide favorable husbandry conditions for maintaining multi-generation populations of this species.

Sexual differentiation in fish occurs after hatching during early life-stages and is believed to be a time when the gonad has a heightened sensitivity to disruption by chemicals that mimic hormones. In this study fathead minnows (Pimephales promelas) were exposed to an environmentally relevant concentration of ethinylestradiol (EE2) for short intervals in fish early life-stages and vitellogenic and gonadal responses were measured at 30 and 100 dph (sexual maturity), respectively. All EE2 exposure regimes induced vitellogenin (VTG) synthesis and disruption in duct development (a feminization) in males, with a window of enhanced sensitivity between 10 and 15 dph (where 60% of the males had feminized ducts). There was an altered pattern in sex cell development in males (inhibition of spermatogenesis) in the solvent controls (ethanol 0.1 ml/l) and all EE2 treatments when compared with the dilution water controls. Furthermore, fewer spermatozoa were observed in the testis of males exposed to EE2 from 15 to 20 dph and fertilized eggs (<24 h post-fertilization)-20 dph, compared with both the solvent and dilution water controls. These data show that short exposures of embryos/very early life-stage fathead minnows to an environmentally relevant concentration of EE2 lead to alterations in gonadal development that potentially have reproductive consequences and thus population level effects.