A New Frontier in Understanding the Mechanisms of Developmental Abnormalities

Kimmel, Carole A.; Generoso, W.M.; Thomas, Robert D.; Bakshi, Kulbir S.

doi:10.1006/taap.1993.1056

Cited by 45 publications

(14 citation statements)

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“…There are at least four distinct levels of biological organization: a ) the subcellular level, which, for example, controls activation versus silencing of portions of the genome (apparently subject to disruption in very early embryos prior to organo-genesis via exposures to agents known for their DNA-damaging properties; Kimmel et al 1993); b ) the cellular level, where there must be controls on pool sizes (concentrations) and turnover rates of key metabolic intermediates, and the adenosine triphosphate energy currency of the cell; c ) the tissue/organ level, where similar and different cell types coordinate their activities to perform physiological functions at required rates, such as the control of blood electrolyte levels by the kidney, the orderly sequential contraction of muscle cells in different parts of the heart, and the coordinated processing of information from the retina to form and identify an image of an object by the brain; d ) the system/organism level, where the activities of multiple systems must be coordinated to accomplish centrally-directed tasks (e.g., the regulation of heart rate, breathing rate, dilation of numerous blood vessels, and muscle activity needed to play soccer).…”

Section: What Is the Mechanism And Consequence Of Interactive Effects?mentioning

confidence: 99%

Assessing Cumulative Health Risks from Exposure to Environmental Mixtures—Three Fundamental Questions

Sexton

Hattis

2007

Environ Health Perspect

136

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Differential exposure to mixtures of environmental agents, including biological, chemical, physical, and psychosocial stressors, can contribute to increased vulnerability of human populations and ecologic systems. Cumulative risk assessment is a tool for organizing and analyzing information to evaluate the probability and seriousness of harmful effects caused by either simultaneous and/or sequential exposure to multiple environmental stressors. In this article we focus on elucidating key challenges that must be addressed to determine whether and to what degree differential exposure to environmental mixtures contributes to increased vulnerability of exposed populations. In particular, the emphasis is on examining three fundamental and interrelated questions that must be addressed as part of the process to assess cumulative risk: a) Which mixtures are most important from a public health perspective? and b) What is the nature (i.e., duration, frequency, timing) and magnitude (i.e., exposure concentration and dose) of relevant cumulative exposures for the population of interest? c) What is the mechanism (e.g., toxicokinetic or toxicodynamic) and consequence (e.g., additive, less than additive, more than additive) of the mixture’s interactive effects on exposed populations? The focus is primarily on human health effects from chemical mixtures, and the goal is to reinforce the need for improved assessment of cumulative exposure and better understanding of the biological mechanisms that determine toxicologic interactions among mixture constituents.

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Section: What Is the Mechanism And Consequence Of Interactive Effects?mentioning

confidence: 99%

Assessing Cumulative Health Risks from Exposure to Environmental Mixtures—Three Fundamental Questions

Sexton

Hattis

2007

Environ Health Perspect

136

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“…Copper deficiency during pregnancy can result in delivery of offspring with congenital abnormalities of the nervous system 11 . It has been reported that more than 50% of human conception fail to implant and of those implanted, approximately 30% fail to reach term due to copper deficiency 12 . However, during pregnancy serum copper level increases from about 80 to 155 µg/dl to about 118 to 302 µg/dl by the end of the 3 rd trimester 9 .…”

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confidence: 99%

Serum Copper and Plasma Protein Status in Normal Pregnancy

Noor¹,

Jahan

Sultana³

2013

J Bangladesh Soc Physiol

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Background: Gradual alteration of serum copper and some plasma protein levels may occur with advancement of pregnancy, which is associated with increased maternal and infant morbidity and mortality. Objective: To observe serum copper and plasma protein levels in normal pregnant women of different trimesters in order to find out their nutritional status. Methods: This cross sectional study was carried out in the Department of Physiology, Sir Salimullah Medical College (SSMC), Dhaka, between 1 st January 2010 and December 2010. Ninety normal pregnant women of different trimesters with age 20-30 years were included in the study group. They were selected from Out Patient Department of Obstetrics and Gynaecology, SSMC. Age matched 30 non-pregnant women were taken as control. Serum copper level was measured by Spectrophotometric method, serum total protein and albumin levels were estimated by standard method. Statistical analysis was done by one way ANOVA, Bonferroni and Pearson's correlation coefficient test as applicable. Results: Serum Cu levels were significantly higher in all trimesters of pregnant women compared to control. Again, this value was significantly higher in 3 rd trimester than that of in 1 st and 2 nd trimester and also in 2 nd trimester than that of in 1 st trimester. In addition, mean serum total protein level was significantly lower in 3 rd trimester than control but no statistically significant difference was observed among different trimesters. Again, mean serum albumin level was significantly lower in 2 nd and 3 rd trimester than 1 st trimester and control. In addition, serum Cu concentration showed significant positive correlation with different trimesters of gestation. Conclusion: This study reveals that hypercupremia along with hypoproteinemia occur in pregnant women from 1 st to 3 rd trimester of gestation. This gradual alteration of micro and macronutrients become more profound with advancement of pregnancy.

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“…Sin embargo, considerando que aproximadamente el 70% de los defectos congénitos son de etiología desconocida, existe ahora evidencia que la exposición durante la etapa de preorganogénesis a ciertos agentes puede conducir a anormalidades fetales como un resultado del daño directo al embrión temprano expuesto (Kimmel et al, 1993). Antes del estado de mórula, los blastomeros individuales del embrión no se encuentran compactados; consecuentemente, todos estan expuestos al ambiente externo en igual grado, pudiendo considerarse a cada blastómero como una entidad independiente por la ausencia de mecanismos regulatorios presentes en un tejido multicelular (Gutierrez-Pajarez, 2000).…”

Section: Discussionunclassified

Embriotoxicidad del bromato de potasio en raton (Mus musculus)

Gonzáles

Pino²

2007

Rev peru biol

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Se evaluó in vivo los efectos de bromato de potasio (KBr0 3 ) sobre el desarrollo de embriones pre- implantacionales de ratón. Ratonas preñadas fueron tratadas con una dosis única de KBr0 3 (68,5 mg/kg de peso corporal; n= 8) y un grupo control (C) tratado con agua destilada (n= 7) en el día 1; al cuarto día de preñez, las hembras fueron sacrifi cadas, los embriones fueron extraidos de los oviductos y de los cuernos uterinos para la evaluación. El KBr0 3 produjo un retraso en el desar- rollo embrionario, encontrándose un 76,9±7,8 y 11,2±5,5 en porcentaje de blastocistos y mórulas respectivamente en el C en comparación de un 34,8±11,2 y 49,3±11,9 de la misma relación en el grupo tratado, mostrando diferencias signifi cativas(p<0,05). En cuanto a la calidad embrionaria, se observó un incremento en el porcentaje de embriones de baja calidad (grado III y degenerados) en el grupo tratado, pero esta diferencia no es estadísticamente signifi cativa (p>0,05). En conclusión podemos decir que el KBr0 3 produce un efecto dañino sobre el embrión, causando retraso en su desarrollo.

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A New Frontier in Understanding the Mechanisms of Developmental Abnormalities

Cited by 45 publications

References 0 publications

Assessing Cumulative Health Risks from Exposure to Environmental Mixtures—Three Fundamental Questions

Assessing Cumulative Health Risks from Exposure to Environmental Mixtures—Three Fundamental Questions

Serum Copper and Plasma Protein Status in Normal Pregnancy

Embriotoxicidad del bromato de potasio en raton (Mus musculus)

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