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Though pesticide mixtures are commonly encountered in fresh water systems, the knowledge of their effects on non-target aquatic species is scarce. The present investigation was undertaken to explore the in vivo inhibition of the freshwater gastropod snail Planorbarius corneus cholinesterase (ChE) and carboxylesterases (CES) activities by the organophosphorus pesticides azinphos-methyl (AZM) and chlorpyrifos (CPF). To this end, snails were exposed for 48 h to different concentrations of AZM and CPF in single-chemical and binary-mixture studies, and ChE and CES activities were measured in the whole soft body tissues and hemolymph. ChE activity was measured with acetylthiocholine as substrate and CES activity was measured with four substrates: p-nitrophenyl acetate, p-nitrophenyl butyrate, 1- and 2-naphthyl acetate. Single-chemical experiments showed that CPF was a more potent inhibitor of ChE activity than AZM (350 and 27 times for the whole soft tissue and hemolymph, respectively). CES were 15 times more sensitive than ChE when the activities were measured in the whole soft tissue of the animals exposed to AZM. Based on a default assumption of concentration addition, P. corneus snails were exposed to mixtures of AZM+CPF designed to yield predicted soft tissue ChE inhibitions of 31% (mixture 1), 50% (mixture 2) and 61% (mixture 3). Results showed that ChE inhibition produced by mixture 1 followed a model of concentration addition. In contrast, the other mixtures showed synergism, both in whole soft tissue and hemolymph. In addition, results obtained when the snails were exposed sequentially to the pesticides showed that the sequence AZM/CPF produced at 48 h a higher ChE inhibition than the sequence CPF/CPF. A range of metabolic pathways and responses associated with bioactivation or detoxification may play important roles in organophosphorus interactions. In particular, the data presented in the present study indicate that CES enzymes would be important factors in determining the effects of the mixtures of OPs on P. corneus ChE activity., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The organochlorine insecticide endosulfan (ES) is widely used despite its high toxicity to fish (96-h LC(50) median value of 2.6 μg L(-1)). This study aimed to assess the acute toxicity, histological and physiological parameters after exposure to 0; 0.25; 1; 2; 3; 4 and 16 μg L(-1) ES for 96 h under semi-static conditions in a freshwater perciform fish, Cichlasoma dimerus. Prior to death, fish exhibited behavior indicative of neurotoxicity. No difference was found in brain AChE activity. A decrease in erythrocyte mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration in exposed fish suggests a state of anemia. Histological alterations observed in exposed fish included hyperplasia of the interlamellar epithelium, blood congestion in secondary lamellae, and mucous cells hyperplasia and hypertrophy in gills; pycnotic nuclei and hydropic degeneration in liver; testicular damage. These moderate pathological responses in major organs could become crucial during reproduction and under prolonged exposure periods., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In this study, some biochemical features and the extent of inhibition induced by the organophosphorous pesticide azinphos-methyl on the cholinesterase (ChE) activity present in whole soft tissue of two freshwater invertebrate species, the gastropod Biomphalaria glabrata and the oligochaete Lumbriculus variegatus were investigated. Both invertebrate organisms presented marked differences in ChE activity, type of enzymes and subcellular location. Acetylthiocholine was the substrate preferred by B. glabrata ChE. The enzyme activity was located preferentially in the supernatant of 11,000 x g centrifugation and was inhibited by increasing concentrations of substrate but not by iso-OMPA. Results showed that there were progressive inhibitions of the enzyme activity, with values 21%, 59%, 72%, 76%, and 82% lower than the control at levels of 1, 10, 50, 100 and 1000 microM of eserine, respectively. In contrast, L. variegatus ChE activity was distributed both in the supernatant and pellet fractions, with values approximately 6 and 20 times higher than B. glabrata, respectively. Studies with butyrylthiocholine and iso-OMPA suggested that about 72% of the activity corresponded to butyrylcholinesterase. A strong enzyme inhibition (88-94%) was found at low eserine concentrations (1-10 microM). ChE activity from L. variegatus and B. glabrata was inhibited by in vivo exposure to azinphos-methyl suggesting that both species can form the oxon derivative of this pesticide. However, both invertebrate species showed a very different susceptibility to the insecticide. The NOEC and EIC50 values were 500 and 1000 times lower for L. variegatus than for B. glabrata, reflecting that the oligochaetes were much more sensitive organisms. A different pattern was also observed for the recovery of the enzymatic activity when the organisms were transferred to clean water. The recuperation process was faster for the oligochaetes than for the gastropods. Mortality was not observed in either of the experimental conditions assayed, not even at concentrations that induced 90% of ChE inhibition. The differences in substrate specificity, sensitivity to inhibitors, and subcellular location between the ChEs of B. glabrata and L. variegatus could be the main factors contributing to the differential susceptibility to azinphos-methyl ChE inhibition found in the present study.

Unlabelled: The risk for premature ovarian failure (POF) in females with galactosemia can be predicted by analyzing 3 areas of risk pathology: the patient's molecular genotype for galactose-1-phosphate uridyltransferase (GALT), alternate pathways for galactose metabolism, and the patient's environment at diagnosis and during treatment., Study Design: Retrospective cross-sectional information was collected on 53 females with classic galactosemia, and their ovarian function was analyzed by determination of serum follicle-stimulating hormone and luteinizing hormone levels and by clinical observation. The associations were analyzed between POF and the mutations in GALT, the highest erythrocyte galactose-1-phosphate (Gal-1-P) level at diagnosis, the age at which dietary treatment was initiated, mean erythrocyte Gal-1-P level during treatment, and whole-body carbon 13-labeled galactose oxidation to (13)CO(2)., Results: The most prevalent mutation, Q188R, had a significant effect of genotype category (Q188R/Q188R, Q188R/Other, Other/Other) on POF (P =.04, Fisher exact test and an odds ratio of 8.3). Mean erythrocyte Gal-1-P level during treatment was a significant risk factor for POF (P =.04). Also, all patients studied with less than 5% total body oxidation of galactose to (13)CO(2) had POF, whereas those with more than 5% did not have POF (P =.008, Fisher exact test)., Conclusion: The development of POF in females with galactosemia is more likely if the patient's genotype is Q188R/Q188R, if the mean erythrocyte Gal-1-P is >3.5 mg/dL during therapy, and if the recovery of (13)CO(2) from whole-body (13)C-galactose oxidation is reduced below 5% of administered (13)C-galactose.

Purpose: This study evaluates a genotype/phenotype relationship between developmental verbal dyspraxia (DVD) and the common, missense mutation of the galactose-1-phosphate uridyltransferase gene, Q188R, in patients with classic galactosemia (G/G)., Methods: As part of this study, we devised a questionnaire for "speech problems" to be completed by the patient\'s clinician. To validate the questionnaire and determine its accuracy in detecting DVD, we analyzed questionnaire responses for 21 patients by testing them independently and directly for DVD through a speech pathologist blinded to the patients' genotype., Results: We found that the questionnaire had a sensitivity of 0.56 and a specificity of 0.75. We then calculated the prevalence of DVD for a larger set of 113 patients with G/G galactosemia whose biochemical phenotype, molecular genotypes, and clinical status were known. The prevalence of "speech problems" from raw data were 50 of 113 (44.2%). After adjusting for misclassification, 43 (38.1%) were classified as cases of DVD. Using multivariate, logistic, regression analyses we found a significant interaction between genotype and mean red blood cell (RBC) galactose-1-phosphate (Gal-1-P). When corrected, using mean RBC Gal-1-P < h 3.28 mg%, the Q188R/Q188R genotype was the best predictor of DVD. There was a significant risk (odds ratio = 9.6, p = 0.0504) of having DVD associated with homozygosity for Q188R compared with other genotypes., Conclusions: We conclude that homozygosity for Q188R mutations in the GALT gene is a significant risk factor for DVD. However, poor metabolic control obviates this relationship as indicated by RBC Gal-1-P greater than 3.28 mg%.