Neurodegenerative Implications of Neuronal Cytoplasmic Protein Dysfunction in Response to Environmental Contaminants.

Neurodegenerative diseases account for a significant portion of public health concerns particularly in the aging population. The dysfunction of interfilament proteins has been identified as a key event in the initiation of neurodegeneration and subsequent progression to neurodegenerative diseases. In addition, several studies have found associations between the dysfunction of interfilament proteins and exposure to environmental contaminants. Therefore, in this review, the role of interfilament proteins in neuronal cells, their connection to neurotoxicity from environmental contaminants, and finally the resulting neurodegeneration are discussed.

Characterization of serotonin following exposure to antibiotics in white-tailed deer.

Developing baseline concentrations of serotonin in healthy white-tailed deer will allow for the development of a biomarker using non-invasive sample tissues in sick animals, for example, non-clinical cases of chronic wasting disease. It will also allow some further insight into whether the use of antibiotics as growth promoters (AGP), such as chlortetracycline, is affecting serotonin concentrations in white-tailed deer. Florfenicol and tulathromycin impacts on serotonin concentration changes were also investigated. An analytical method for the detection and confirmation of serotonin, 5-hydroxytryptamine (5-HT), in white-tailed deer tissues was developed and validated. Serum and urine samples were extracted with acetonitrile. Liquid chromatography separation was attained on a Phenomenex C18 column with a Security Guard ULTRA guard column with gradient elution using a mobile phase of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. This methodology was applied to baseline (control), chlortetracycline (CTC) treated, florfenicol treated and tulathromycin treated white-tailed deer serum and urine samples.

Qualitative and quantitative drug residue analyses: Chlortetracycline in white-tailed deer (Odocoileus virginianus) and supermarket meat by liquid chromatography tandem-mass spectrometry.

Chlortetracycline is (CTC) is a tetracycline antibiotic which is being in the white-tailed deer industry to improve production and animal health. In this paper, we present a method for determining chlortetracycline residues in edible white-tailed deer tissues, using liquid chromatography with heated electrospray ionization and mass spectrometry detection. The procedure involved extraction with EDTA-McIlvaine buffer at pH 4.0, followed by solid-phase extraction cleanup using a hydrophilic-lipophilic balance (HLB) cartridge. The liquid chromatography analysis was performed with heated electrospray ionization and mass spectrometry detection. The limit of quantification for the method was 2.7 ng/g and limit of detection was 0.8 ng/g. The recovery values were >78.5% for muscle, 65.1% for kidney, 63.1% for liver. Mean tissue residue concentration of chlortetracycline and it's epimer, 4-epi chlortetracycline (4-epi-CTC) at 10-day withdrawal period for kidney, liver, muscle was 122.8, 44.7 and 26.7 ng/g, respectively. Chlortetracycline tissue residue concentration at 45-day withdrawal period for kidney, liver, muscle was 19.2, 28.9 and 10.7 ng/g, respectively. Mean tissue concentration of CTC was less than the established maximum residual limit (MRL) values for bovine tissues. We have validated and successfully applied this method in the qualitative and quantification of chlortetracycline in white-tailed deer tissue samples.

Assessment of gonadal and thyroid histology in Gulf killifish (Fundulus grandis) from Barataria Bay Louisiana one year after the Deepwater Horizon oil spill.

We examined gonads and thyroid glands of Gulf killifish (Fundulus grandis) 1yr after the Deepwater Horizon oil spill. F. grandis were trapped from two impacted sites in Barataria Bay (Bayou St. Denis, Bay Jimmy) and an un-impacted site in East Texas (Sabine Pass). The greatest number of F. grandis were collected at Sabine Pass. F. grandis collected at Bayou St. Denis were smaller and had smaller Fulton condition factor scores than fish collected at Sabine Pass. Sex ratios were biased roughly 2:1 in favor of females at Sabine Pass and Bayou St. Denis. Gonad-somatic index (GSI) in males from Sabine Pass was double that of fish from Bay Jimmy while germinal epithelium thickness of the testes was 2.7 fold smaller in males from the impacted site. GSI and oocyte diameters in females from Bayou St. Denis were significantly smaller than females from Bay Jimmy or the reference site. There were no differences in thyroid follicle cell height. While total polyaromatic hydrocarbons at the impacted sites were no different from the reference site, the impacted sites did have greater concentrations of benzo[a]pyrene in sediment pore water. The finding of smaller GSI and testicular germinal epithelium in males from an impacted site suggest that exposure to a combination of oil and dispersants may adversely impact testicular function.

Qualitative and Quantitative Drug residue analyses: Florfenicol in white-tailed deer (Odocoileus virginianus) and supermarket meat by liquid chromatography tandem-mass spectrometry.

A method for confirmation and detection of Florfenicol amine residues in white-tailed deer tissues was developed and validated in our laboratory. Tissue samples were extracted with ethyl acetate and cleaned up on sorbent (Chem-elut) cartridges. Liguid chromatography (LC) separation was achieved on a Zorbax Eclipse plus C18 column with gradient elution using a mobile phase composed of ammonium acetate in water and methanol at a flow rate of 300µL/min. Qualitative and quantitative analyses were carried out using liquid chromatography - heated electrospray ionization(HESI) and atmospheric pressure chemical ionization (APCI)-tandem mass spectrometry in the multiple reaction monitoring (MRM) interface. The limits of detection (LODs) for HESI and APCI probe were 1.8ng/g and 1.4ng/g respectively. Limits of quantitation (LOQs) for HESI and APCI probe were 5.8ng/g and 3.4ng/g respectively. Mean recovery values ranged from 79% to 111% for APCI and 30% to 60% for HESI. The validated method was used to determine white-tailed deer florfenicol tissue residue concentration 10-days after exposure. Florfenicol tissue residues concentration ranged from 0.4 to 0.6µg/g for liver and 0.02-0.05µg/g for muscle and a trace in blood samples. The concentration found in the tested edible tissues were lower than the maximum residual limit (MRL) values established by the federal drug administration (FDA) for bovine tissues. In summary, the resulting optimization procedures using the sensitivity of HESI and APCI probes in the determination of florfenicol in white-tailed deer tissue are the most compelling conclusions in this study, to the extent that we have applied this method in the evaluation of supermarket samples drug residue levels as a proof of principle.

Changes in gastric sodium-iodide symporter (NIS) activity are associated with differences in thyroid gland sensitivity to perchlorate during metamorphosis.

We investigated stage-dependent changes in sensitivity of the thyroid gland to perchlorate during development of African clawed frog tadpoles (Xenopus laevis) in relation to non-thyroidal iodide transporting tissues. Perchlorate-induced increases in thyroid follicle cell size and colloid depletion were blunted when exposures began at Nieuwkoop-Faber (NF) stage 55 compared to when exposures began at NF stages 49 or 1-10. To determine if the development of other iodide transporting tissues may contribute to this difference we first examined which tissues expressed transcripts for the sodium dependent iodide symporter (NIS). RT-PCR analysis revealed that NIS was expressed in stomach and small intestine in addition to the thyroid gland of X. laevis tadpoles. NIS mRNA was not detected in lung, kidney, skin, gill, muscle, heart or liver. Perchlorate sensitive (125)I uptake was found in stomach, lung, kidney, gill, and small intestine but not muscle, liver, or heart. Perchlorate-sensitive (125)I uptake by stomach was 6-10 times greater than in any other non-thyroidal tissue in tadpoles. While NF stage 49 tadpoles exhibited perchlorate-sensitive uptake in stomach it was roughly 4-fold less than that observed in NF stage 55 tadpoles. Although abundance of NIS gene transcripts was greater in stomachs from NF stage 55 compared to NF stage 49 tadpoles this difference was not statistically significant. We conclude that gastric iodide uptake increases between NF stages 49 and 55, possibly due to post-translational changes in NIS glycosylation or trafficking within gastric mucosal cells. These developmental changes in gastric NIS gene expression may affect iodide availability to the thyroid gland.

Lyophilized tea extracts of Brickellia cavanillesii (Asteraceae): in vitro characterization of biological activity.

UNLABELLED: Lyophilized Brickellia cavanillesii (LBC) tea extracts and identified chemical compounds of LBC were examined using in vitro human carcinoma liver (HepG2) cells with and without fetal bovine serum (FBS). Cells were incubated for 24 h with varying concentrations of FBS and LBC, respectively; cytotoxicity was determined spectrophotometrically using MTT (Formazan 3-(4,5-dimethyl-thiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide) assay. Furthermore, the potential hypoglycemic activity of LBC tea extracts was investigated using glucose transport and metabolism proteins biomarkers. FBS (0% to 10%) increased the viability of HepG2 cells steadily with increasing concentration. Possible therapeutic effects of LBC were concentration dependent with and without FBS. The cytotoxicity of 12 identified compounds from the LBC extract suggests that the individual compounds inhibited the proliferation of HepG2 cells differentially and do not reflect the inhibition of the whole aqueous LBC. Western blot analysis of glucose facilitated transporter protein 2 (GLUT 2) expression of HepG2 cells exposed to 0 mg/mL (Control) and 0.2 mg/mL LBC for 2, 4, 6, and 24 h suggests that GLUT 2 expression was increased. Increase in GLUT 2 expression in the absence of FBS was statistically significant with time of exposure. Significant difference was observed for GLUT 2 expression between 6 and 24 h and also between 4 and 24 h at 0.2 mg/mL LBC. Results obtained indicate that LBC may exhibit antidiabetic activity. However, further studies will be necessary to clearly delineate LBC potential therapeutic benefit and biological activities in animal studies as well as other in vitro models. PRACTICAL APPLICATION: Brickellia cavanillesii (Asteraceae) is a herbal plant widely used (Central America, Mexico and South-Western U.S.A.) in Type 2 diabetes mellitus therapy. Unfortunately, there is insufficient scientific data to validate its presumed pharmacological properties. This study examines the cytotoxic properties of whole, and certain identified chemical compounds in B. cavanillesii. It also investigates the potential hypoglycemic activity of lyophilized B. cavanillesii using glucose transport and metabolism proteins as biomarkers.

Chemical characterization of Brickellia cavanillesii (Asteraceae) using gas chromatographic methods.

A methanol extract of lyophilized Brickellia cavanillesii was quantitatively analyzed using gas chromatographic (GC) techniques. The chromatographic methods employed were (i) GC-flame ionization detector (GC-FID), (ii) GC-mass spectrometry (GC-MS), and (iii) purge and trap GC-MS (P&T GC-MS). Thirteen compounds were identified with a quality match of 90% and above using GC-MS. The compounds were (1) Cyclohexene, 6-ethenyl-6-methyl-1-(1-methylethyl)-3-(1-methylethylidene)-, (S)-; (2) Bicylo (2.2.1) heptan-2-one, 1, 7, 7-trimethyl-(1S, 4S)-; (3) Phenol, 2-methoxy-4-(1-propenyl)-; (4) Benzene, 1-(1, 5-dimethyl-4-hexenyl)-4-methyl-; (5) Naphthalene, 1, 2, 3, 5, 6, 8a-hexahydro4, 7-dimethyl-1-1-(1-methylethyl)-, (1S-cis)-; (6) Phenol, 2-methoxy-; (7) Benzaldehyde, 3-hydroxy-4-methoxy-; (8) 11, 13-Eicosadienoic acid, methyl ester; (9) 2-Furancarboxaldehyde, 5-methyl-; (10) Maltol; (11) Phenol; (12) Hydroquinone; (13) 1H-Indene, 1-ethylideneoctahydro-7a-methyl-, (1E, 3a.alpha, 7a.beta.). Other compounds (14) 3-methyl butanal; (15) (D)-Limonene; (16) 1-methyl-4-(1-methyl ethyl) benzene; (17) Butanoic acid methyl ester; (18) 2-methyl propanal; (19) 2-butanone; (20) 2-pentanone; and (21) 2-methyl butane were also identified when P&T GC-MS was performed. Of the 21 compounds identified, 12 were validated using chemical standards. The identified compounds were found to be terpenes, derivatives of terpenes, esters, ketones, aldehydes, and phenol-derived aromatic compounds; these are the primary constituents of the essential oils of many plants and flowers.

An intrinsic CRF signaling system within the optic tectum.

Previous work indicates that CRF administration inhibits visually guided feeding in amphibians. We used the African clawed frog Xenopus laevis to examine the hypothesis that CRF acts as a neurotransmitter in the optic tectum, the major brain area integrating the visual and premotor pathways regulating visually guided feeding in anurans. Reverse transcriptase PCR revealed that cells in the optic tectum express mRNA for CRF and the CRF R1 receptor but not the CRF R2 receptor. Radioligand binding studies indicated that specific binding of [(125)I]-Tyr-oCRF to tectal cell membranes can be displaced by the CRF R1 antagonists antalarmin or NBI-27914. CRF increased the expression of mRNA encoding regulator of G-protein signaling 2 (rgs2) in tectal explants and this effect was blocked by antalarmin. CRF had no effect on basal glutamate or gamma-aminobutyric acid (GABA) secretion but inhibited secretion of norepinephrine from tectal explants, an effect that completely blocked by antalarmin. Using a homologous radioimmunoassay we determined that CRF release from tectal explants in vitro was potassium- and calcium-dependent. Basal and depolarization-induced CRF secretion was greater from optic tectum than hypothalamus/thalamus, telencephalon, or brainstem. We concluded that the optic tectum possesses a CRF signaling system that may be involved in modulating communication between sensory and motor pathways involved in food intake.

Routine delivery of artemisinin-based combination treatment at fixed health facilities reduces malaria prevalence in Tanzania: an observational study.

BACKGROUND: Artemisinin-based combination therapy (ACT) has been promoted as a means to reduce malaria transmission due to their ability to kill both asexual blood stages of malaria parasites, which sustain infections over long periods and the immature derived sexual stages responsible for infecting mosquitoes and onward transmission. Early studies reported a temporal association between ACT introduction and reduced malaria transmission in a number of ecological settings. However, these reports have come from areas with low to moderate malaria transmission, been confounded by the presence of other interventions or environmental changes that may have reduced malaria transmission, and have not included a comparison group without ACT. This report presents results from the first large-scale observational study to assess the impact of case management with ACT on population-level measures of malaria endemicity in an area with intense transmission where the benefits of effective infection clearance might be compromised by frequent and repeated re-infection. METHODS: A pre-post observational study with a non-randomized comparison group was conducted at two sites in Tanzania. Both sites used sulphadoxine-pyrimethamine (SP) monotherapy as a first-line anti-malarial from mid-2001 through 2002. In 2003, the ACT, artesunate (AS) co-administered with SP (AS + SP), was introduced in all fixed health facilities in the intervention site, including both public and registered non-governmental facilities. Population-level prevalence of Plasmodium falciparum asexual parasitaemia and gametocytaemia were assessed using light microscopy from samples collected during representative household surveys in 2001, 2002, 2004, 2005 and 2006. FINDINGS: Among 37,309 observations included in the analysis, annual asexual parasitaemia prevalence in persons of all ages ranged from 11% to 28% and gametocytaemia prevalence ranged from <1% to 2% between the two sites and across the five survey years. A multivariable logistic regression model was fitted to adjust for age, socioeconomic status, bed net use and rainfall. In the presence of consistently high coverage and efficacy of SP monotherapy and AS + SP in the comparison and intervention areas, the introduction of ACT in the intervention site was associated with a modest reduction in the adjusted asexual parasitaemia prevalence of 5 percentage-points or 23% (p < 0.0001) relative to the comparison site. Gametocytaemia prevalence did not differ significantly (p = 0.30). INTERPRETATION: The introduction of ACT at fixed health facilities only modestly reduced asexual parasitaemia prevalence. ACT is effective for treatment of uncomplicated malaria and should have substantial public health impact on morbidity and mortality, but is unlikely to reduce malaria transmission substantially in much of sub-Saharan Africa where individuals are rapidly re-infected.

Effects of chronic 2,4,6,-trinitrotoluene, 2,4-dinitrotoluene, and 2,6-dinitrotoluene exposure on developing bullfrog (Rana catesbeiana) tadpoles.

Chronic aqueous exposures were conducted using bullfrog (Rana catesbeiana) tadpoles (8 d old) exposed to TNT (0-4 mg/L), 2,4-DNT (0-4 mg/L), and 2,6-DNT (0-8 mg/L) for 90 d. Survival of tadpoles examined using Cox proportional hazard models was reduced at all concentrations tested. Percent of abnormal swimming and other morphological abnormalities after sublethal exposure to TNT, 2,4-DNT, and 2,6-DNT at 2 mg/L were also evaluated. The effects of TNT, 2,4-DNT, and 2,6-DNT on wet body mass, snout vent length (SVL), and developmental stage of surviving tadpoles were examined. Only 2,4-DNT did not have a significant effect on body mass or SVL, but all three compounds tested had significant effects on survival. Long-term continuous exposure to these compounds at concentrations of 0.25 mg/L could lead to significant changes in growth and survival of larval amphibians.

Expression of steroidogenic acute regulatory protein (StAR) in male American bullfrog (Rana catesbeiana) and preliminary evaluation of the response to TNT.

We examined the expression of steroidogenic acute regulatory (StAR) protein mRNA in the American bullfrog (Rana catesbeiana). Primers and probes were designed to obtain a partial sequence of bullfrog StAR cDNA consisting of 349 base pairs. Quantitative PCR analysis of StAR mRNA equivalents was performed in tissues of juvenile and adult bullfrogs. In this study 18S mRNA was used as an internal standard. There were no differences in the expression of 18S RNA among tissues or between age groups. In juvenile males, the rank order for the constitutive levels of StAR was testes>skin>brain>kidneys. In adult males, StAR mRNA equivalent was greatest in testes, followed by kidneys, brain, and skin. In addition, stimulation and induction of testicular StAR by human chorionic gonadotropin significantly increased expression of StAR at 2, 4, and 6h after injection. Preliminary evaluation of 2, 4, 6-trinitrotoluene (TNT) revealed that acute exposure is associated with reduction of StAR mRNA expression. The information provided in this study will be useful for future research on StAR gene expression in amphibian reproductive biology and the development of reproductive biomarkers.

Effects of atrazine on fish, amphibians, and aquatic reptiles: a critical review.

The herbicide atrazine is widely used in agriculture for the production of corn and other crops. Because of its physical and chemical properties, atrazine is found in small concentrations in surface waters--habitats for some species. A number of reports on the effects of atrazine on aquatic vertebrates, mostly amphibians, have been published, yet there is inconsistency in the effects reported, and inconsistency between studies in different laboratories. We have brought the results and conclusions of all of the relevant laboratory and field studies together in this critical review and assessed causality using procedures for the identification of causative agents of disease and ecoepidemiology derived from Koch's postulates and the Bradford-Hill guidelines. Based on a weight of evidence analysis of all of the data, the central theory that environmentally relevant concentrations of atrazine affect reproduction and/or reproductive development in fish, amphibians, and reptiles is not supported by the vast majority of observations. The same conclusions also hold for the supporting theories such as induction of aromatase, the enzyme that converts testosterone to estradiol. For other responses, such as immune function, stress endocrinology, parasitism, or population-level effects, there are no indications of effects or there is such a paucity of good data that definitive conclusions cannot be made.

Acute toxicity of 2,4,6-trinitrotoluene, 2,4-dinitrotoluene, and 2,6-dinitrotoluene in the adult bullfrog (Lithobates catesbeiana).

2,4,6-Trinitrotoluene (TNT) is one of the most prevalent high explosives in the environment. 2,4-Dinitrotoluene (2,4-DNT) and 2,6-dinitrotoluene (2,6-DNT) are the most common isoforms of dinitrotoluene. The goal of this study was to determine the acute toxic effects of TNT, 2,4-DNT, and 2,6-DNT in adult male bullfrogs. The LD(50) for TNT was 1,060 mg/kg BW while the LD(50 )for 2,4-DNT and 2,6-DNT was 1,098 mg/kg BW. All three compounds elicited similar symptoms of toxicity including changes of skin color, body weight, development of seizures, liver and kidney necrosis, and lung cyanosis. Relative organ weights did not show significant change.

Effects of larval exposure to estradiol on spermatogenesis and in vitro gonadal steroid secretion in African clawed frogs, Xenopus laevis.

Estrogen or eco-estrogenic chemicals can disrupt normal gonadal sex differentiation, causing intersex formation and feminization in amphibians. The cellular basis for estrogen-induced sex reversal is not well understood. In the present study, we investigated the concentration- and stage-dependent effects of estradiol (E(2)) exposure during the larval period on histological characteristics of gonadal sex differentiation and gonadal sex steroid secretion in vitro in the African clawed frog, Xenopus laevis. Embryos were exposed to E(2) (1, 10, or 100 microg/L) or vehicle control through metamorphosis and then allowed to develop in untreated medium for 2-mo post-metamorphosis. To investigate gonadal sex differentiation and development during and after exposure, gonadal samples were collected at different developmental stages. Gonadal sex differentiation did not occur before NF stage 52 in any group. At NF stage 54-55 primordial germ cells (PGCs) were observed in both cortical and medullary regions of developing tadpoles gonads in the control, 1 and 10 microg/L E(2) treatments, but were observed only in the cortical region of tadpoles exposed to 100 microg/L E(2). E(2) increased the percent of spermatocytes, spermatids, and spermatozoa compared to controls. Larval E(2) exposure did not alter hCG-induced gonadal testosterone secretion in vitro but significantly increased E(2) secretion from ovaries of juvenile frogs. Our results indicate that E(2) exposure during larval development appears to prevent PGC migration to the medulla of developing gonads in a concentration-dependent manner. The degree of PGC migration to the medulla may be related to the degree of E(2)-induced intersex formation and feminization in X. laevis. E(2) exposure during the larval period accelerates spermatogenesis and can increase ovarian E(2) secretion in juvenile frogs.

Reproduction, larval growth, and reproductive development in African clawed frogs (Xenopus laevis) exposed to atrazine.

Reproductive success and development of F2 offspring from F1 adult African clawed frogs (Xenopus laevis) exposed to atrazine throughout larval development and as sexually mature adults was examined. Larval X. laevis were exposed to one of four nominal concentrations of atrazine (0, 1, 10, 25 microg atrazine/l) beginning 96 hr after fertilization and continuing through two years post-metamorphosis. Clutch size and survival of offspring were used as measurement endpoints to gauge reproductive success of the F1 frogs. Larval survivorship and time to metamorphosis were used to gauge developmental success of the F2 offspring from atrazine-exposed frogs. Testes in F1 and F2 frogs were examined for incidence of anomalies, such as testicular ovarian follicles, and sex ratios in F2 offspring were investigated to determine if exposure to atrazine caused trans-generational effects (effects on F2 individuals due to exposure of F1 individuals). There were no effects of any of the studied concentrations of atrazine on clutch size of F1 frogs. There were also no effects on hatching success or time to metamorphosis. Sex ratios did not differ between F2 offspring among treatments. There was no evidence to suggest a transgenerational effect of atrazine on spawning success or reproductive development of X. laevis. This is consistent with the presence of robust populations of X. laevis in areas where they are exposed to atrazine that has been used for several decades for weed control in production of corn. Our observations also are consistent with the results of most other studies of frogs where no effects were found to be associated with exposure to atrazine. Our data do not support the hypothesis that atrazine significantly affects reproductive fitness and development of frogs.

Fatty acid profile in milk from goats, Capra aegagrus hircus, exposed to perchlorate and its relationship with perchlorate residues in human milk.

Polyunsaturated fatty acids (PUFA) in milk are vital for normal growth and development of infant mammals. Changes in fatty acid composition were observed in milk fat from goats dosed with perchlorate (0.1 and 1 mg/kg body weight/day) for 31 days, but the effect was not persistent. Adaptation may be induced in these goats to compensate for the perchlorate effect. In an analysis of fatty acid composition in human milk samples, a weak negative correlation was observed between perchlorate concentrations and total PUFA in 38 human milk samples.

Effects of perchlorate on sodium-iodide symporter and pendrin gene expression in deer mice.

Effects of perchlorate on sodium-iodide symporter (NIS) and pendrin gene expression in deer mice kidney and stomach were investigated. This was accomplished by isolating a partial cDNA sequence of deer mice NIS gene of 425 bps, and quantitatively analyzing NIS mRNA expression in various deer mouse tissues. The highest NIS expression level was in the stomach, followed by testes, brain, and large intestine; very low expression of NIS was observed in the lung, kidney, heart, and liver. Exposure to perchlorate through drinking water for 28 days did not significantly increase NIS gene expression in the kidney and stomach, and pendrin gene expression in the kidney. In a depuration experiment in which deer mice were exposed to perchlorate for 8-h followed by an 88-h depuration period, no significant difference was observed between the low and high exposure groups in terms of NIS or pendrin gene expression in the kidney or stomach at the end of the experiment. Furthermore, no significant linear relationship was observed between gene expression (either NIS or pendrin) in the kidney and perchlorate mass excreted via urine at day 28, average daily excretion, or total excretion mass over the 28 day exposure. Several factors could influence the effect of perchlorate exposure on NIS and pendrin gene expression in the stomach and kidney, including (1) pre-exposure to trace perchlorate through food and water perhaps resulting in adaptation (or tolerance) in these animals; (2) metabolism of perchlorate in deer mice causing only 46-61% perchlorate excreted into urine. It is also possible that there is no effect of perchlorate exposure and/or urinary excretion on NIS and pendrin gene expression, particularly in the kidney.

HIV immunosuppression and antimalarial efficacy: sulfadoxine-pyrimethamine for the treatment of uncomplicated malaria in HIV-infected adults in Siaya, Kenya.

BACKGROUND: The altered immune response of persons with human immunodeficiency virus (HIV) infection could result in increased rates of antimalarial treatment failure. We investigated the influence of HIV infection on the response to sulfadoxine-pyrimethamine treatment. METHODS: Febrile adults with Plasmodium falciparum parasitemia were treated with sulfadoxine-pyrimethamine and were monitored for 28 days. HIV status and CD4 cell count were determined at study enrollment. RESULTS: Of the adults enrolled in the study, 508 attended all follow-up visits, including 130 HIV-uninfected adults, 256 HIV-infected adults with a high CD4 cell count (> or =200 cells/ micro L), and 122 HIV-infected adults with a low CD4 cell count (<200 cells/ micro L). The hazard of treatment failure at day 28 of follow-up was significantly higher for HIV-infected adults with a low CD4 cell count (20.5%) than for HIV-uninfected adults (7.7%). Anemia (hemoglobin level, <110 g/L) modified the effect of HIV status on treatment failure. When we controlled for fever and parasite density, the hazard of treatment failure for HIV-infected adults with a low CD4 cell count and anemia was 3.4 times higher than that for HIV-uninfected adults (adjusted hazard ratio, 3.38; 95% confidence interval, 1.56-7.34). CONCLUSIONS: HIV-infected persons with a low CD4 cell count and anemia have an increased risk of antimalarial treatment failure. The response to malaria treatment in HIV-infected persons must be carefully monitored. Proven measures for the control and prevention of malaria must be incorporated into the basic package of services provided by HIV/acquired immunodeficiency syndrome care and treatment programs in malarious areas.

Age-dependent characterization of pendrin gene expression in various tissues of deer mice.

Pendrin is a membrane transport protein which functions as the transporter of chloride, bicarbonate, formate, and iodide. In this study, we characterized pendrin gene expression in various tissues of deer mice (Peromyscus maniculatus), a sentinel wildlife species. Deer mice were euthanized at post-natal day (PND) 21 (day of weaning) and PND 45 (24 days post-weaning) for tissue collection. A deer mouse-specific partial pendrin cDNA sequence was generated, from which Taqman-specific probe and primers were designed for quantification of mRNA equivalents of pendrin gene expression using real-time polymerase chain reaction (PCR). The expression profile was standardized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Results indicate that the pendrin gene was expressed at different levels in the different tissues of developing deer mice relative to GAPDH expression. Expression in the tissues was determined to be age-dependent. Pendrin gene was highly expressed in the kidney, lungs and reproductive tissues. PND 21 expression in the kidney and testes was significantly lower than PND 45. This study represents the first identification of differential expression of pendrin gene in various deer mouse tissues.