RESUMEN
This study aimed to assess the iodine status of pregnant women in each trimester and to compare the pregnancy outcomes between groups with iodine insufficiency and iodine sufficiency. Longitudinal study on urinary iodine concentration (UIC) in each trimester as well as comparison between women with iodine insufficiency (<150 mcg L(-1) ) and iodine sufficiency was conducted. Pregnant women without thyroid diseases who had not received iodine supplementation were recruited for UIC measurements in each trimester and were followed up for pregnancy outcomes. In the analysis of 384, 325 and 221 samples in the first, second and third trimester, the medians of UICs were 147.39, 157.01 and 153.07 mcg L(-1) , respectively. Of 399 women, 174 (43.6%) had a UIC less than 150 mcg L(-1) (suggesting iodine insufficiency) and 225 (56.4%) had a UIC greater than or equal to 150 mcg L(-1) (suggesting iodine sufficiency). Of 390 women with availability of the final outcomes, 171 and 219 in the insufficiency and sufficiency group, respectively, the rates of preterm birth and low birthweight were significantly higher in the insufficiency group, 17.5% vs. 10.0% (P = 0.031) and 19.9% vs. 12.3% (P = 0.042), respectively. Logistic regression analysis showed that iodine status was an independent risk of preterm birth and low birthweight. Finally, women with a UIC <100 mcg L(-1) had a significantly higher rate of fetal growth restriction, 13/68 vs. 30/322 (P = 0.031). In northern Thailand, a great number of pregnant women had a median UIC less than 150 mcg L(-1) and they had a higher risk of preterm birth and low birthweight. Finally, those with a median UIC of less than 100 mcg L(-1) had a higher risk of fetal growth restriction.
Asunto(s)
Retardo del Crecimiento Fetal/epidemiología , Yodo/deficiencia , Yodo/orina , Resultado del Embarazo , Nacimiento Prematuro/epidemiología , Adulto , Suplementos Dietéticos , Femenino , Retardo del Crecimiento Fetal/orina , Humanos , Modelos Logísticos , Estudios Longitudinales , Persona de Mediana Edad , Estado Nutricional , Embarazo , Nacimiento Prematuro/orina , Factores de Riesgo , Tailandia/epidemiologíaRESUMEN
BACKGROUND: Pyrethroid insecticides, especially permethrin and deltamethrin, have been used extensively worldwide for mosquito control. However, insecticide resistance can spread through a population very rapidly under strong selection pressure from insecticide use. The upregulation of aldehyde dehydrogenase (ALDH) has been reported upon pyrethroid treatment. In Aedes aegypti, the increase in ALDH activity against the hydrolytic product of pyrethroid has been observed in DDT/permethrin-resistant strains. The objective of this study was to identify the role of individual ALDHs involved in pyrethroid metabolism. METHODOLOGY/PRINCIPAL FINDINGS: Three ALDHs were identified; two of these, ALDH9948 and ALDH14080, were upregulated in terms of both mRNA and protein levels in a DDT/pyrethroid-resistant strain of Ae. aegypti. Recombinant ALDH9948 and ALDH14080 exhibited oxidase activities to catalyse the oxidation of a permethrin intermediate, phenoxybenzyl aldehyde (PBald), to phenoxybenzoic acid (PBacid). CONCLUSIONS/SIGNIFICANCE: ALDHs have been identified in association with permethrin resistance in Ae. aegypti. Characterisation of recombinant ALDHs confirmed the role of this protein in pyrethroid metabolism. Understanding the biochemical and molecular mechanisms of pyrethroid resistance provides information for improving vector control strategies.
Asunto(s)
Aedes/genética , Aldehído Deshidrogenasa/metabolismo , Resistencia a los Insecticidas/genética , Control de Mosquitos , Piretrinas/farmacología , Aedes/enzimología , Aldehído Deshidrogenasa/genética , Animales , Regulación hacia Arriba/efectos de los fármacosRESUMEN
The Epsilon glutathione transferase (GST) class in the dengue vector Aedes aegypti consists of eight sequentially arranged genes spanning 53,645 bp on super contig 1.291, which maps to chromosome 2. One Epsilon GST, GSTE2, has previously been implicated in conferring resistance to DDT. The amino acid sequence of GSTE2 in an insecticide susceptible and a DDT resistant strain differs at five residues two of which occur in the putative DDT binding site. Characterization of the respective recombinant enzymes revealed that both variants have comparable DDT dehydrochlorinase activity although the isoform from the resistant strain has higher affinity for the insecticide. GSTe2 and two additional Epsilon GST genes, GSTe5 and GSTe7, are expressed at elevated levels in the resistant population and the recombinant homodimer GSTE5-5 also exhibits low levels of DDT dehydrochlorinase activity. Partial silencing of either GSTe7 or GSTe2 by RNA interference resulted in an increased susceptibility to the pyrethroid, deltamethrin suggesting that these GST enzymes may also play a role in resistance to pyrethroid insecticides.
Asunto(s)
Aedes/efectos de los fármacos , Aedes/genética , DDT/farmacología , Glutatión Transferasa/genética , Nitrilos/farmacología , Piretrinas/farmacología , Aedes/metabolismo , Secuencia de Aminoácidos , Animales , DDT/metabolismo , Femenino , Regulación de la Expresión Génica , Glutatión Transferasa/metabolismo , Resistencia a los Insecticidas , Liasas/metabolismo , Masculino , Datos de Secuencia Molecular , Nitrilos/metabolismo , Piretrinas/metabolismoRESUMEN
Glutathione transferases (GSTs) (E.C.2.5.1.18) are multifunctional enzymes involved in the detoxification of many exogenous and endogenous compounds. This study aimed to characterize several new GSTs from Anopheles cracens, a major Thai malaria vector formerly known as Anopheles dirus. The three recombinant enzymes obtained were from the epsilon, theta and omega classes. They showed 80-93% identity to orthologous An. gambiae GSTs. AcGSTE2-2 possessed peroxidase activity that cannot be detected for the An. gambiae AgGSTE2-2. AcGSTT1-1 had high activity toward several substrates that are specific for mammalian theta class. The AcGSTO1-1 can use 1-chloro-2,4-dinitrobenzene, dichloroacetic acid, and hydroxyethyl disulfide substrates. The enzymes bound but did not metabolize the organophosphate temephos. The epsilon AcGSTE2-2 functioned as a peroxidase and DDT metabolizing enzyme. The theta AcGSTT1-1 functioned not only as peroxidase but also acted as a binding protein for organophosphates. The omega GST had thiol transferase activity suggesting a role in oxidative stress response.
Asunto(s)
Anopheles/enzimología , Anopheles/genética , Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo , Insectos Vectores/enzimología , Malaria/transmisión , Secuencia de Aminoácidos , Animales , Regulación Enzimológica de la Expresión Génica , Humanos , Insectos Vectores/genética , Malaria/epidemiología , Datos de Secuencia Molecular , Filogenia , Tailandia/epidemiologíaRESUMEN
Glutathione transferases, GSTs, are detoxification proteins that are found in most organisms. The acGSTE3-3 had the ability to conjugate 4-hydroxynonenal, a cytotoxic lipid peroxidation product. Although other Epsilon GSTs showed roles in insecticide metabolism, the acGSTE3-3 appeared to have a major role in detoxifying lipid peroxidation products conferring protection against oxidative damage.
Asunto(s)
Anopheles/enzimología , Glutatión Transferasa/genética , Secuencia de Aminoácidos , Animales , Clonación Molecular , Glutatión Transferasa/antagonistas & inhibidores , Glutatión Transferasa/metabolismo , Resistencia a los Insecticidas/fisiología , Cinética , Datos de Secuencia Molecular , Familia de Multigenes , Nitrilos/farmacología , Permetrina/farmacología , Piretrinas/farmacología , Alineación de Secuencia , Especificidad por SustratoRESUMEN
The study was designed to investigate the problem of endemic goiter and iodine supplementation in Mae Hong Son, Thailand. Routine school data still showed high goiter rates in many areas. Six such schools and five schools with declining prevalence of goiter were selected. A single examiner examined all the children. Their weight, height, body mass index, ethnicity, history of iodine intake and migration were recorded. Urine samples were collected for measuring iodine and thiocyanate levels. From 653 children, 105 and 13 were found to have grade 1 and 2 goiter status, respectively. Median values of urine iodine level in children from all schools suggested sufficient iodine supplementation. Multivariate analysis showed that hilltribe minorities had a 2.09 times higher risk of endemic goiter than Thai children. Urine thiocyanate levels among children from high prevalence schools were significantly higher than those from low prevalence schools. No other significant correlation was found. Possible roles of other known and unknown goitrogens should also be investigated.